Δευτέρα, 23 Ιανουαρίου 2017

Osteomyelitis

Osteomyelitis: Inflammation of the bone due to infection, for example, by the bacteria salmonella or staphylococcus. Osteomyelitis is sometimes a complication of surgery or injury, although infection can also reach bone tissue through the bloodstream. Both the bone and the bone marrow may be infected. Symptoms include deep pain and muscle spasms in the area of inflammation, as well as fever. Treatment includes bed rest, use of antibiotics, and sometimes surgery to remove dead bone tissue.



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Combination of Metformin with Chemotherapeutic Drugs via Different Molecular Mechanisms

Metformin, a widely prescribed drug for treating type II diabetes, is one of the most extensively recognized metabolic modulators which has shown an important anti-cancer property. However, fairly amount of clinical trials on its single administration have not demonstrated a convincing efficiency yet. Thus, recent studies tend to combine metformin with clinical commonly used chemotherapeutic drugs to decrease their toxicity and attenuate their tumor resistance. These strategies have displayed promising clinical benefits.

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Editorial Board

Publication date: January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1867, Issue 1





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Reviewer Acknowledgement

Publication date: January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1867, Issue 1





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Publisher Note

Publication date: January 2017
Source:Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Volume 1867, Issue 1





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Cloud-Based DDoS HTTP Attack Detection Using Covariance Matrix Approach

In this era of technology, cloud computing technology has become essential part of the IT services used the daily life. In this regard, website hosting services are gradually moving to the cloud. This adds new valued feature to the cloud-based websites and at the same time introduces new threats for such services. DDoS attack is one such serious threat. Covariance matrix approach is used in this article to detect such attacks. The results were encouraging, according to confusion matrix and ROC descriptors.

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A Design of a New Column-Parallel Analog-to-Digital Converter Flash for Monolithic Active Pixel Sensor

The CMOS Monolithic Active Pixel Sensor (MAPS) for the International Linear Collider (ILC) vertex detector (VXD) expresses stringent requirements on their analog readout electronics, specifically on the analog-to-digital converter (ADC). This paper concerns designing and optimizing a new architecture of a low power, high speed, and small-area 4-bit column-parallel ADC Flash. Later in this study, we propose to interpose an S/H block in the converter. This integration of S/H block increases the sensitiveness of the converter to the very small amplitude of the input signal from the sensor and provides a sufficient time to the converter to be able to code the input signal. This ADC is developed in 0.18 μm CMOS process with a pixel pitch of 35 μm. The proposed ADC responds to the constraints of power dissipation, size, and speed for the MAPS composed of a matrix of 64 rows and 48 columns where each column ADC covers a small area of 35 × 336.76 μm2. The proposed ADC consumes low power at a 1.8 V supply and 100 MS/s sampling rate with dynamic range of 125 mV. Its DNL and INL are 0.0812/−0.0787 LSB and 0.0811/−0.0787 LSB, respectively. Furthermore, this ADC achieves a high speed more than 5 GHz.

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Kinetics of Rituximab Excretion into Urine and Peritoneal Fluid in Two Patients with Nephrotic Syndrome

Clinical observations suggest that treatment of Rituximab might be less effective in patients with nephrotic range proteinuria when compared to nonnephrotic patients. It is conceivable that the reason for this is that significant amounts of Rituximab might be lost in the urine in a nephrotic patient and that these patients require a repeated or higher dosage. However, this has not been systematically studied. In this case report we describe two different patients with nephrotic range proteinuria receiving Rituximab. The first patient received Rituximab for therapy resistant cryoglobulinemic membranoproliferative glomerulonephritis and the other for second line treatment of Felty’s syndrome. We employed flow cytometry to determine the amount of Rituximab excretion in both urine and peritoneal fluid specimens in these patients following administration of Rituximab. We found that a significant amount of Rituximab is lost from the circulation by excretion into the urine. Furthermore we saw a close correlation of the excretion of Rituximab to the excretion of IgG molecules suggesting selectivity of proteinuria as the determining factor of Rituximab excretion. Further larger scale clinical studies could have the potential to evaluate an optimal cut-off value of IgG urinary loss before a possible administration of Rituximab therefore contributing to a more individualized treatment approach in patients with nonselective and nephrotic range proteinuria.

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Beneficial Effects of Paeoniflorin Enriched Extract on Blood Pressure Variability and Target Organ Damage in Spontaneously Hypertensive Rats

Blood pressure variability (BPV) is associated with the development and progression of severe target organ damage (TOD). This study aims to evaluate the protective effect of paeoniflorin enriched extract from Radix Paeoniae Alba (PG) on BPV and TOD in spontaneously hypertensive rats (SHR). All SHR were orally treated with distilled water, metoprolol (MP, 20 mg/kg), and PG (PG-H, 90 mg/kg or PG-L, 30 mg/kg) for a single time or daily for 7 weeks. The 24-hour dynamic blood pressure was monitored and then calculated BPV including long- and short-term systolic blood pressure variability (SBPV), diastolic blood pressure variability (DBPV), mean blood pressure variability (MBPV), and heart rate variability (HRV) as well as the 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP. The protective effects of PG on TOD were observed by histopathologic and biochemical detection. The results indicated that long- and short-term SBPV, DBPV, MBPV, and HRV as well as 24-hour-SBP, 24-hour-DBP, and 24-hour-MBP showed no significant changes after single-dose administration of PG and significantly decreased after administration with PG for 7 weeks. PG could also markedly improve the damage of aorta, heart, kidney, and brain. This study suggested that PG could notably reduce BPV, stabilize blood pressure, and mitigate TOD in SHR.

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Thermodynamics of the Schwarzschild-AdS Black Hole with a Minimal Length

Using the mass-smeared scheme of black holes, we study the thermodynamics of black holes. Two interesting models are considered. One is the self-regular Schwarzschild-AdS black hole whose mass density is given by the analogue to probability densities of quantum hydrogen atoms. The other model is the same black hole but whose mass density is chosen to be a rational fractional function of radial coordinates. Both mass densities are in fact analytic expressions of the -function. We analyze the phase structures of the two models by investigating the heat capacity at constant pressure and the Gibbs free energy in an isothermal-isobaric ensemble. Both models fail to decay into the pure thermal radiation even with the positive Gibbs free energy due to the existence of a minimal length. Furthermore, we extend our analysis to a general mass-smeared form that is also associated with the -function and indicate the similar thermodynamic properties for various possible mass-smeared forms based on the -function.

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Assessing the Impacts of the 2009/2010 Drought on Vegetation Indices, Normalized Difference Water Index, and Land Surface Temperature in Southwestern China

Droughts are projected to increase in severity and frequency on both regional and global scales. Despite the increasing occurrence and intensity of the 2009/2010 drought in southwestern China, the impacts of drought on vegetation in this region remain unclear. We examined the impacts of the 2009/2010 drought in southwestern China on vegetation by calculating the standardized anomalies of Normalized Difference Vegetation Index (NDVI), Enhanced Vegetation Index (EVI), Normalized Difference Water Index (NDWI), and Land Surface Temperature (LST). The standardized anomalies of NDVI, EVI, and NDWI exhibited positively skewed frequency distributions, while the standardized anomalies of LST exhibited a negatively skewed frequency distribution. These results implied that the NDVI, EVI, and NDWI declined, while LST increased in the 2009/2010 drought-stricken vegetated areas during the drought period. The responses of vegetation to the 2009/2010 drought differed substantially among biomes. Savannas, croplands, and mixed forests were more vulnerable to the 2009/2010 drought than deciduous forest and grasslands, while evergreen forest was resistant to the 2009/2010 drought in southwestern China. We concluded that the 2009/2010 drought had negative impacts on vegetation in southwestern China. The resulting assessment on the impacts of drought assists in evaluating and mitigating its adverse effects in southwestern China.

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CNS Metastases from Bone and Soft Tissue Sarcomas in Children, Adolescents, and Young Adults: Are They Really So Rare?

Purpose. To check whether primary involvement of brain/spinal cord by bone/soft tissue sarcomas’ metastases in children is as rare as described and to present various morphological forms of bone/soft tissue sarcomas’ CNS metastases. Methods. Patients with first diagnosis in 1999–2014 treated at single center were included with whole course of disease evaluation. Brain/spinal canal magnetic resonance imaging (MRI)/computed tomography were performed in cases suspicious for CNS metastases. Extension from skull/vertebral column metastases was excluded. Results. 550 patients were included. MRI revealed CNS metastases in 19 patients (incidence 3.45%), 14 boys, aged 5–22 years. There were 12/250 osteosarcoma cases, 2/200 Ewing’s sarcoma, 1/50 chondrosarcoma, 3/49 rhabdomyosarcoma (RMS), and 1/1 malignant mesenchymoma. There were 10 single metastases and 7 cases of multiple ones; in 2 RMS cases only leptomeningeal spread in brain and spinal cord was found. Calcified metastases were found in 3 patients and hemorrhagic in 4. In one RMS patient there were numerous solid, cystic, hemorrhagic lesions and leptomeningeal spread. Conclusions. CNS metastases are rare and late in children with bone/soft tissue sarcomas, although in our material more frequent (3.45%) than in other reports (0.7%). Hematogenous spread to brain and hemorrhagic and calcified lesions dominated in osteosarcoma. Ewing sarcoma tended to metastasize to skull bones. Soft tissue sarcomas presented various morphological forms.

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Acupuncture Improved Neurological Recovery after Traumatic Brain Injury by Activating BDNF/TrkB Pathway

How to promote neural repair following traumatic brain injury (TBI) has long been an intractable problem. Although acupuncture has been demonstrated to facilitate the neurological recovery, the underlying mechanism is elusive. Brain-derived neurotrophic factor (BDNF) exerts substantial protective effects for neurological disorders. In this study, we found that the level of BDNF and tropomyosin receptor kinase B (TrkB) was elevated spontaneously after TBI and reached up to the peak at 12 h. Nevertheless, this enhancement is quickly declined to the normal at 48 h. After combined stimulation at the acupoints of Baihui, Renzhong, Hegu, and Zusanli, we found that BDNF and TrkB were still significantly elevated at 168 h. We also observed that the downstream molecular p-Akt and p-Erk1/2 were significantly increased, suggesting that acupuncture could persistently activate the BDNF/TrkB pathway. To further verify that acupuncture improved recovery through activating BDNF/TrkB pathway, K252a (specific inhibitor of TrkB) was treated by injection stereotaxically into lateral ventricle. We observed that K252a could significantly prevent the acupuncture-induced amelioration of motor, sensation, cognition, and synaptic plasticity. These data indicated that acupuncture promoted the recovery of neurological impairment after TBI by activating BDNF/TrkB signaling pathway, providing new molecular mechanism for understanding traditional therapy of acupuncture.

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A New Method Based on Laplace Transform and Its Application to Stability of Pipe Conveying Fluid

A new differential transformation method is developed in this paper and is applied for free vibration problem of pipes conveying fluid. The natural frequencies, critical flow velocities, and vibration mode functions of such pipes with several typical boundary conditions are obtained and compared with the results predicted by Galerkin method and finite element method (FEM) and with other results archived. The results show that the present method is of high precision and can serve as an analytical method for the vibration of pipes conveying fluid.

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Utilizing Selected Di- and Trinucleotides of siRNA to Predict RNAi Activity

Small interfering RNAs (siRNAs) induce posttranscriptional gene silencing in various organisms. siRNAs targeted to different positions of the same gene show different effectiveness; hence, predicting siRNA activity is a crucial step. In this paper, we developed and evaluated a powerful tool named “siRNApred” with a new mixed feature set to predict siRNA activity. To improve the prediction accuracy, we proposed 2-3NTs as our new features. A Random Forest siRNA activity prediction model was constructed using the feature set selected by our proposed Binary Search Feature Selection (BSFS) algorithm. Experimental data demonstrated that the binding site of the Argonaute protein correlates with siRNA activity. “siRNApred” is effective for selecting active siRNAs, and the prediction results demonstrate that our method can outperform other current siRNA activity prediction methods in terms of prediction accuracy.

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Energy Near-Optimal Control Strategies for Industrial and Traction Drives with a.c. Motors

The main contribution of this paper is a new rest-to-rest position control system for use with electric drives employing a.c. motors that is near-optimal with respect to combined electrical and frictional energy waste minimization. The friction has constant, linear, and quadratic components with respect to the rotor speed. The closeness to optimality is assessed by simulation, comparing the energy loss of the new control system with that predicted by computed optimal controls. The application of the near-optimal control system is rendered straightforward by using a symmetrical trapezoidal speed-time profile. This is provided by an energy saving reference position generator whose output is faithfully followed by means of a feedback control law based on forced dynamics control yielding prescribed closed loop dynamics, together with a matched zero dynamic lag precompensator. For load torque consisting of constant, linear, and quadratic components also maneuver time is optimized if it can be chosen arbitrary. Two case studies, one applied to position control of rotational drive and second one applied to train movement, confirm the possibilities of achieving energy savings.

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Intranasal Delivery of miR-146a Mimics Delayed Seizure Onset in the Lithium-Pilocarpine Mouse Model

Unveiling the key mechanism of temporal lobe epilepsy (TLE) for the development of novel treatments is of increasing interest, and anti-inflammatory miR-146a is now considered a promising molecular target for TLE. In the current study, a C57BL/6 TLE mouse model was established using the lithium-pilocarpine protocol. The seizure degree was evaluated according to the Racine scale, and level 5 was considered the threshold for generalized convulsions. Animals were sacrificed to analyze the hippocampus at three time points (2 h and 4 and 8 weeks after pilocarpine administration to evaluate the acute, latent, and chronic phases, resp.). After intranasal delivery of miR-146a mimics (30 min before pilocarpine injection), the percent of animals with no induced seizures increased by 6.7%, the latency to generalized convulsions was extended, and seizure severity was reduced. Additionally, hippocampal damage was alleviated. While the relative miR-146a levels significantly increased, the expression of its target mRNAs (IRAK-1 and TRAF-6) and typical inflammatory modulators (NF-κB, TNF-α, IL-1β, and IL-6) decreased, supporting an anti-inflammatory role of miR-146a via the TLR pathway. This study is the first to demonstrate that intranasal delivery of miR-146a mimics can improve seizure onset and hippocampal damage in the acute phase of lithium-pilocarpine-induced seizures, which provides inflammation-based clues for the development of novel TLE treatments.

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Unilateral Head Impulses Training in Uncompensated Vestibular Hypofunction

The aim of this paper is to report a case of a young woman with unilateral vestibular chronic failure with a poorly compensated vestibuloocular reflex during rapid head rotation. Additionally, she developed migraine symptoms during the treatment with associated chronic dizzy sensations and blurred vision. Her report of blurred vision only improved after she completed a rehabilitation program using fast head impulse rotations towards the affected side for 5 consecutive days. We discuss why we elected this form of treatment and how this method may be useful for different patients.

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Efficacy of Memantine in Schizophrenic Patients: A Systematic Review

Several evidences support the hypothesis that glutamatergic dysfunction may be implicated in the pathogenesis of schizophrenia and in the last few years great interest has been focused on the role of the N-methyl-D-aspartate receptor (NMDAR). Glutamate is the main excitatory neurotransmitter in human CNS and it plays a prominent role in synaptic plasticity, learning, and memory and other cognitive functions. Increasing interest in memantine add-on therapy in schizophrenic patients with negative and cognitive symptoms may suggest that memantine could be a new promising treatment in schizophrenia. The aim of this update was to evaluate clinical data about the memantine effectiveness in schizophrenic patients. Our systematic review of the literature highlights that memantine therapy in schizophrenic patients seems to improve mainly negative symptoms while positive symptoms and cognitive symptoms did not improve significantly.

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Electrowetting Actuation of Polydisperse Nanofluid Droplets

We present results of electrowetting experiments employing droplets formed from aqueous suspensions of Au nanoparticles. A planar electrowetting system, consisting of a Pt wire electrode and a bottom Cu electrode with an insulating silicone layer, is used to observe changes in droplet contact angle when an external electric field is applied. The equilibrium contact angle at 0 V decreases with increasing nanoparticle concentration, dropping from 100.4° for pure deionized water to 94.7° for a 0.5 μM nanofluid. Increasing the nanoparticle content also lowers the required voltage for effective actuation. With actuation at 15 V, contact angle decreases by 9% and 35% for droplets formed from pure water and a 0.5 μM nanoparticle suspension, respectively. Contact angle saturation is observed with nanofluid droplets, with the threshold voltage decreasing as nanoparticle concentration rises. Maximum droplet actuation before contact angle saturation is achieved at only 10 V for a concentration of 0.5 μM. A proposed mechanism for the enhanced electrowetting response of a nanofluid droplet involves a reduction in surface tension of the droplet as nanoparticles accumulate at the liquid-vapor interface.

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Two Different Cell Populations Is an Important Clue for Diagnosis of Primary Cutaneous Adenoid Cystic Carcinoma: Immunohistochemical Study

Primary cutaneous adenoid cystic carcinoma (PCACC) is a very rare malignancy. The differential diagnosis of PCACCs in pathology practice can be difficult and a group of primary and metastatic lesions, including adenoid basal cell carcinoma of the skin, should be considered in the differential diagnosis. Besides histomorphological clues, immunohistochemistry studies are very helpful in the differential diagnosis of PCACC. We report herein a case of PCACC with extensive immunohistochemical studies and review the literature from an immunohistochemistry perspective.

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Aspalatone Prevents VEGF-Induced Lipid Peroxidation, Migration, Tube Formation, and Dysfunction of Human Aortic Endothelial Cells

Although aspalatone (acetylsalicylic acid maltol ester) is recognized as an antithrombotic agent with antioxidative and antiplatelet potential; its efficacy in preventing endothelial dysfunction is not known. In this study, we examined the antiangiogenic, antioxidative, and anti-inflammatory effect of aspalatone in human aortic endothelial cells (HAECs). Specifically, the effect of aspalatone on VEGF-induced HAECs growth, migration, tube formation, and levels of lipid peroxidation-derived malondialdehyde (MDA) was examined. Our results indicate that the treatment of HAECs with aspalatone decreased VEGF-induced cell migration, tube formation, and levels of MDA. Aspalatone also inhibited VEGF-induced decrease in the expression of eNOS and increase in the expression of iNOS, ICAM-1, and VCAM-1. Aspalatone also prevented the VEGF-induced adhesion of monocytes to endothelial cells. Furthermore, aspalatone also prevented VEGF-induced release of inflammatory markers such as Angiopoietin-2, Leptin, EGF, G-CSF, HB-EGF, and HGF in HAECs. Thus, our results suggest that aspalatone could be used to prevent endothelial dysfunction, an important process in the pathophysiology of cardiovascular diseases.

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Assessing the Association between Serum Ferritin, Transferrin Saturation, and C-Reactive Protein in Northern Territory Indigenous Australian Patients with High Serum Ferritin on Maintenance Haemodialysis

Objective. To determine the significance of high serum ferritin observed in Indigenous Australian patients on maintenance haemodialysis in the Northern Territory, we assessed the relationship between ferritin and transferrin saturation (TSAT) as measures of iron status and ferritin and C-reactive protein (CRP) as markers of inflammation. Methods. We performed a retrospective cohort analysis of data from adult patients (≥18 years) on maintenance haemodialysis (>3 months) from 2004 to 2011. Results. There were 1568 patients. The mean age was 53.9 (11.9) years. 1244 (79.3%) were Indigenous. 44.2% () were male. Indigenous patients were younger (mean age [52.3 (11.1) versus 57.4 (15.2), ]) and had higher CRP [14.7 mg/l (7–35) versus 5.9 mg/l (1.9–17.5), ], higher median serum ferritin [1069 µg/l (668–1522) versus 794.9 µg/l (558.5–1252.0), ], but similar transferrin saturation [26% (19–37) versus 28% (20–38), ]. We observed a small positive correlation between ferritin and TSAT (, ), no correlation between ferritin and CRP ( = 0.001, ), and positive association between high serum ferritin and TSAT (), Indigenous ethnicity (), urea reduction ratio (), and gender () after adjustment in mixed regression analysis. Conclusion. Serum ferritin and TSAT may inadequately reflect iron status in this population. The high ferritin was poorly explained by inflammation.

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Mutation Analysis of HTRA2 Gene in Chinese Familial Essential Tremor and Familial Parkinson’s Disease

Background. HTRA2 has already been nominated as PARK13 which may cause Parkinson’s disease, though there are still discrepancies among these results. Recently, Gulsuner et al.’s study found that HTRA2 p.G399S is responsible for hereditary essential tremor and homozygotes of this allele develop Parkinson’s disease by examining a six-generation family segregating essential tremor and essential tremor coexisting with Parkinson’s disease. We performed this study to validate the condition of HTRA2 gene in Chinese familial essential tremor and familial Parkinson’s disease patients, especially essential tremor. Methods. We directly sequenced all eight exons, exon-intron boundaries, and part of the introns in 101 familial essential tremor patients, 105 familial Parkinson’s disease patients, and 100 healthy controls. Results. No exonic variant was identified, while one exon-intron boundary variant (rs2241028) and one intron variant (rs2241027) were detected, both with no clinical significance and uncertain function. There was no difference in allele, genotype, and haplotype between groups. Conclusions. HTRA2 exonic variant might be rare among Chinese Parkinson’s disease and essential tremor patients with family history, and HTRA2 may not be the cause of familial Parkinson’s disease and essential tremor in China.

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Hedgehog Pathway Inhibition Hampers Sphere and Holoclone Formation in Rhabdomyosarcoma

Rhabdomyosarcoma (RMS) is the most common type of soft tissue sarcoma in children and can be divided into two main subtypes: embryonal (eRMS) and alveolar (aRMS). Among the cellular heterogeneity of tumors, the existence of a small fraction of cells called cancer stem cells (CSC), thought to be responsible for the onset and propagation of cancer, has been demonstrated in some neoplasia. Although the existence of CSC has been reported for eRMS, their existence in aRMS, the most malignant subtype, has not been demonstrated to date. Given the lack of suitable markers to identify this subpopulation in aRMS, we used cancer stem cell-enriched supracellular structures (spheres and holoclones) to study this subpopulation. This strategy allowed us to demonstrate the capacity of both aRMS and eRMS cells to form these structures and retain self-renewal capacity. Furthermore, cells contained in spheres and holoclones showed significant Hedgehog pathway induction, the inhibition of which (pharmacologic or genetic) impairs the formation of both holoclones and spheres. Our findings point to a crucial role of this pathway in the maintenance of these structures and suggest that Hedgehog pathway targeting in CSC may have great potential in preventing local relapses and metastases.

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Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors

The genomic alterations identified in head and neck squamous cell carcinoma (HNSCC) tumors have not resulted in any changes in clinical care, making the development of biomarker-driven targeted therapy for HNSCC a major translational gap in knowledge. To fill this gap, we used 59 molecularly characterized HNSCC cell lines and found that mutations of AJUBA,SMAD4 and RAS predicted sensitivity and resistance to treatment with inhibitors of polo-like kinase 1 (PLK1), checkpoint kinases 1 and 2, and WEE1.

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IgG trough levels and progression of pulmonary disease in pediatric and adult CVID patients

Capsule summary: Common variable immunodeficiency patients show silent progression of airway disease which was inversely correlated to IgG trough levels. A randomized controlled study into optimal IgG through levels to prevent pulmonary disease progression is warranted.

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Defects in Lymphocyte Telomere Homeostasis Contribute to Cellular Immune phenotype in Cartilage-Hair Hypoplasia

Patients with CHH often have lymphopenia and impaired lymphocyte proliferation. These defects appear to result from altered lymphocyte telomere homeostasis and may confer susceptibilities to infection and malignancy for the patient with CHH.

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Football team raises money for McKinney teacher battling cancer - FOX 4 News


FOX 4 News

Football team raises money for McKinney teacher battling cancer
FOX 4 News
MCKINNEY, Texas - A McKinney teacher battling cancer got some help she didn't expect that came thanks to a program at McKinney Boyd High School. The program is called “Purple Out. Every year, the football team surprises people who are battling cancer ...



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Mutations of the LIM protein AJUBA mediate sensitivity of head and neck squamous cell carcinoma to treatment with cell-cycle inhibitors

The genomic alterations identified in head and neck squamous cell carcinoma (HNSCC) tumors have not resulted in any changes in clinical care, making the development of biomarker-driven targeted therapy for HNSCC a major translational gap in knowledge. To fill this gap, we used 59 molecularly characterized HNSCC cell lines and found that mutations of AJUBA,SMAD4 and RAS predicted sensitivity and resistance to treatment with inhibitors of polo-like kinase 1 (PLK1), checkpoint kinases 1 and 2, and WEE1.

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Adolescents with Mild Traumatic Brain Injury Get SMART: An Analysis of a Novel Web-Based Intervention

Telemedicine and e-Health , Vol. 0, No. 0.


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“Go! to Sleep”: A Web-Based Therapy for Insomnia

Telemedicine and e-Health , Vol. 0, No. 0.


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Did Someone Hit the Reset Button?

Telemedicine and e-Health , Vol. 0, No. 0.


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Healthcare Usage after Uvulopalatopharyngoplasty – Impact of Analgesic Regimen

1) Analyze differences in healthcare usage between subjects receiving different perioperative analgesic medications after uvulopalatopharyngoplasty (UPPP) surgery. 2) Comment on the impact of perioperative analgesic medication on length of hospital stay and complications after UPPP.

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Paradoxical Vocal Fold Motion (PVFM) in Pediatric Otolaryngology

Paradoxical vocal fold motion (PVFM) is a condition in which the vocal cords exhibit inappropriate inspiratory adduction, and it has been poorly studied in the pediatric population.

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Auricular transverse muscle shortening as an adjunct to perichondrium-sparing Mustarde otoplasty

Recently, our article entitled “Antitragicus muscle resection: a key to correction of prominent lobules” was published in this journal.1 In addition to malposition or overdevelopment of the antitragicus muscle causing protrusion of the earlobe, abnormal development of other auricular muscles is also thought to contribute to prominent ears. Yotsuyanagi et al.2 reported that an elongated auricular transverse muscle was associated with poor development of the antihelical fold. Therefore, we attempted to refine the Mustarde otoplasty by performing auricular transverse muscle shortening as an adjunct procedure.

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Reply to the letter to the editor “Robotic-assisted Nipple Sparing Mastectomy: A feasibility study on cadaveric models” by Sarfati B. et al

We read with interest the paper by Sarfati et al. [1] reporting a feasibility study on robotic nipple sparing mastectomy on cadaveric models. We acknowledge and we recognize in this report the resourcefulness and geniality of using the new robotic technology to perform one of the operation most frequently performed of all cancer surgery such as mastectomy.

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The Ulnar Artery Perforator Adipofascial flap: an alternative for vascularised coverage of the Median Nerve

Vascularised tissue for coverage of the median nerve after surgery for persistant or recurrent carpal tunnel syndrome can be a challenging problem. Persistence of median nerve symptoms is consistent with incomplete decompression[1]. Recurrence is documented carpal tunnel syndrome where there was an initially resolution of symptoms following initial decompression[2]. Persistence and recurrence of symptoms may be of differing aetiologies but all must be considered in the management of this difficult problem.

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Effects of DMSO on Rabbit Ear Hypertrophic Scar Model: A Controlled Randomized Experimental Study

Dimethylsulfoxide (DMSO) is an anti-inflammatory, anti-bacterial, analgesic drug that is widely used to treat several diseases in literature. It has a detractive effect to collagen deposition in abnormal tissue. The aim of this study was to investigate the possible therapeutic effects of the DMSO in the hypertrophic scar formation in rabbit.Twenty-four New Zealand male albino rabbits were randomly divided into four groups: control, sham, DMSO, and TRA (triamcinolone acetonide). Except control group, punch biopsy defects were created on each animal’s right ear.

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Two-stage treatment of ischial pressure ulcers in spinal cord injury patients: Technique and outcomes over 8-years

Reconstruction of ischial pressure ulcers remains a difficult problem with high reported failure rates, despite newly introduced techniques.

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The Glasgow Anterior Stabilisation (GAS) Appliance - A Novel Orthodontic Appliance for Pre-Maxillary Stabilisation in Bilateral Cleft Lip and Palate

We are writing to describe our experience of the Glasgow Anterior Stabilization (GAS) appliance: A novel fixed orthodontic that we have found to be very useful in the stabilization of the pre-maxilla in patients with bilateral cleft lip and palate. The GAS appliance offers easy application and removal and is optimized to provide good surgical access to the cleft site for bone grafting or osteotomy. We have successfully used this appliance in a series of 10 cases and have found it to be very clinically versatile.

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Breast implants rupture induced by fatigue phenomena

The authors have no commercial associations or financial disclosures that might pose or create a conflict of interest with information presented in this article. No funding was received for this work.

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Association between soil heavy metals and fatty liver disease in men in Taiwan: a cross sectional study

Objectives

Metabolic factors are major risk factors for non-alcoholic fatty liver disease although other factors may also contribute to development of fatty liver disease. We explored the association between exposure to soil heavy metals and prevalence of fatty liver disease.

Methods

We retrospectively analysed data from patients diagnosed with fatty liver disease in 2014 at the Health Evaluation Centre of Chang-Hua Christian Hospital (n=1137). We used residency data provided in the records of the Health Evaluation Centre and data for soil metal concentrations from a nationwide survey conducted by the Environmental Protection Administration of Taiwan. We studied the correlations between the severity of fatty liver disease and concentrations of soil heavy metals (arsenic, mercury, cadmium, chromium, copper, nickel, lead and zinc).

Results

The prevalence of moderate to severe fatty liver disease in our study was 26.5%. Using univariate and multivariate analysis, we demonstrated that the presence of soil heavy metals was a significant risk factor for fatty liver disease in men (OR 1.83, 95% CI 1.161 to 2.899, p=0.009). With stratification by body mass index (BMI) and gender, lean men with a BMI <24 kg/m2 were the most susceptible to soil heavy metals (OR 5.059, 95% CI 1.628 to 15.728, p<0.05).

Conclusions

Our study suggested a significant association between exposure to soil heavy metals and fatty liver disease in lean men.



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Protocol of a randomised controlled, open-label trial of ex vivo normothermic perfusion versus static cold storage in donation after circulatory death renal transplantation

Introduction

Ex vivo normothermic perfusion (EVNP) is a novel technique that reconditions the kidney and restores renal function prior to transplantation. Phase I data from a series of EVNP in extended criteria donor kidneys have established the safety and feasibility of the technique in clinical practice.

Methods and analysis

This is a UK-based phase II multicentre randomised controlled trial to assess the efficacy of EVNP compared with the conventional static cold storage technique in donation after circulatory death (DCD) kidney transplantation. 400 patients receiving a kidney from a DCD donor (categories III and IV, controlled) will be recruited into the study. On arrival at the transplant centre, kidneys will be randomised to receive either EVNP (n=200) or remain in static cold storage (n=200). Kidneys undergoing EVNP will be perfused with an oxygenated packed red cell solution at near body temperature for 60 min prior to transplantation. The primary outcome measure will be determined by rates of delayed graft function (DGF) defined as the need for dialysis in the first week post-transplant. Secondary outcome measures include incidences of primary non-function, the duration of DGF, functional DGF defined as <10% fall in serum creatinine for 3 consecutive days in the first week post-transplant, creatinine reduction ratio days 2 and 5, length of hospital stay, rates of biopsy-proven acute rejection, serum creatinine and estimated glomerular filtration rate at 1, 3, 6 and 12 months post-transplant and patient and allograft survival. The EVNP assessment score will be recorded and the level of fibrosis and inflammation will also be measured using tissue, blood and urine samples. Ethics and dissemination. The study has been approved by the National Health Service (NHS) Health Research Authority Research Ethics Committee. The results are expected to be published in 2020.

Trial registration number

ISRCTN15821205; Pre-results.



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Correction

Gavin AT, Donnelly D, Donnelly C, et al. Effect of investigation intensity and treatment differences on prostate cancer survivor's physical symptoms, psychological well-being and health-related quality of life: a two country cross-sectional study. BMJ Open 2016;6:e012952.

The contributions are incorrect. They should read as follows;

Contributors ATG, LS, CD and FJD were involved in conception of study, funding and ethics. ATG and DD were involved in data analysis. FJD, ATG, LS and GJG were involved in study organisation. All authors were involved in data interpretation and write-up.



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Cohort study investigating the effects of first stage of the English tobacco point-of-sale display ban on awareness, susceptibility and smoking uptake among adolescents

Objective

A prospective evaluation of the effect of 2012 point-of-sale (PoS) display ban in supermarkets in England on perceived exposure to PoS displays, and on changes in susceptibility and smoking uptake among young people.

Design

Cohort study.

Settings

Seven schools in Nottinghamshire, England.

Participants

1035 11–16-year-old school children.

Primary and secondary outcome measures

Changes in reported exposure to PoS displays before and after prohibition, and the association between exposure to and awareness of PoS displays and change in susceptibility to smoking and smoking status between 2011 and 2012 (before the ban) and 2012 and 2013 (after the ban).

Results

The proportion of children noticing tobacco PoS displays in supermarkets most or every time they visited a shop changed little between 2011 and 2012 (59.6% (95% CI 56.6% to 62.6%) and 58.8% (95% CI 55.8% to 61.8%), respectively); but decreased by about 13 percentage points to 45.7% (95% CI 42.7% to 48.7%) in 2013, after the ban. However, after adjusting for confounders, implementation of the first stage of the PoS ban in 2012 did not result in significant changes in the relation between susceptibility to smoking and smoking status and exposure to and awareness of PoS displays.

Conclusions

Prohibition of PoS in large supermarkets resulted in a decline in the proportion of young people noticing PoS displays in large shops, but little or no change in smoking uptake or susceptibility. It remains to be seen whether extension of the PoS ban to all shops in 2015 has a more marked effect.



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Correction

Johansen PP, Zwisler A-D, HastrupSvendsen J, et al. The CopenHeartSF trial— comprehensive sexual rehabilitation programme for male patients with implantable cardioverter defibrillator or ischaemic heart disease and impaired sexual function: protocol of a randomised clinical trial. BMJ Open 2013;3:e003967.

There has been an update to the Statistical Analyses Plan. The new Statistical Analysis section should read:

Statistical analysis

The analysis will follow the intention-to-treat principle with two-sided significance test at the 5% level. Continuous outcomes will follow the same procedure as described in the following for the primary outcome. The primary outcome is the International Index of Erectile Function overall score. The five domains of the questionnaire are all exploratory outcome, but particular attention is given the Erectile Function domain. The secondary outcome is PAIS-SR sexual relationship domain.

The explorative physical outcomes are pelvic floor strength and endurance (one categorical and two continuous variables), peak VO2, heart...



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Capacity of English NHS hospitals to monitor quality in infection prevention and control using a new European framework: a multilevel qualitative analysis

Objective

(1) To assess the extent to which current English national regulations/policies/guidelines and local hospital practices align with indicators suggested by a European review of effective strategies for infection prevention and control (IPC); (2) to examine the capacity of local hospitals to report on the indicators and current use of data to inform IPC management and practice.

Design

A national and local-level analysis of the 27 indicators was conducted. At the national level, documentary review of regulations/policies/guidelines was conducted. At the local level data collection comprised: (a) review of documentary sources from 14 hospitals, to determine the capacity to report performance against these indicators; (b) qualitative interviews with 3 senior managers from 5 hospitals and direct observation of hospital wards to find out if these indicators are used to improve IPC management and practice.

Setting

2 acute English National Health Service (NHS) trusts and 1 NHS foundation trust (14 hospitals).

Participants

3 senior managers from 5 hospitals for qualitative interviews.

Primary and secondary outcome measures

As primary outcome measures, a ‘Red-Amber-Green’ (RAG) rating was developed reflecting how well the indicators were included in national documents or their availability at the local organisational level. The current use of the indicators to inform IPC management and practice was also assessed. The main secondary outcome measure is any inconsistency between national and local RAG rating results.

Results

National regulations/policies/guidelines largely cover the suggested European indicators. The ability of individual hospitals to report some of the indicators at ward level varies across staff groups, which may mask required improvements. A reactive use of staffing-related indicators was observed rather than the suggested prospective strategic approach for IPC management.

Conclusions

For effective patient safety and infection prevention in English hospitals, routine and proactive approaches need to be developed. Our approach to evaluation can be extended to other country settings.



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Risk of cardiovascular events, arrhythmia and all-cause mortality associated with clarithromycin versus alternative antibiotics prescribed for respiratory tract infections: a retrospective cohort study

Objective

To determine whether treatment with clarithromycin for respiratory tract infections was associated with an increased risk of cardiovascular (CV) events, arrhythmias or all-cause mortality compared with other antibiotics.

Design

Retrospective cohort design comparing clarithromycin monotherapy for lower (LRTI) or upper respiratory tract infection (URTI) with other antibiotic monotherapies for the same indication.

Setting

Routine primary care data from the UK Clinical Practice Research Datalink and inpatient data from the Hospital Episode Statistics (HES).

Participants

Patients aged ≥35 years prescribed antibiotic monotherapy for LRTI or URTI 1998–2012 and eligible for data linkage to HES.

Main outcome measures

The main outcome measures were: adjusted risk of first-ever CV event, within 37 days of initiation, in commonly prescribed antibiotics compared with clarithromycin. Secondarily, adjusted 37-day risks of first-ever arrhythmia and all-cause mortality.

Results

Of 700 689 treatments for LRTI and eligible for the CV analysis, there were 2071 CV events (unadjusted event rate: 29.6 per 10 000 treatments). Of 691 998 eligible treatments for URTI, there were 688 CV events (9.9 per 10 000 treatments). In LRTI and URTI, there were no significant differences in CV risk between clarithromycin and all other antibiotics combined: OR=1.00 (95% CI 0.82 to 1.22) and 0.82 (0.54 to 1.25), respectively. Adjusted CV risk in LRTI versus clarithromycin ranged from OR=1.42 (cefalexin; 95% CI 1.08 to 1.86) to 0.92 (doxycycline; 0.64 to 1.32); in URTI, from 1.17 (co-amoxiclav; 0.68 to 2.01) to 0.67 (erythromycin; 0.40 to 1.11). Adjusted mortality risk versus clarithromycin in LRTI ranged from 0.42 to 1.32; in URTI, from 0.75 to 1.43. For arrhythmia, adjusted risks in LRTI ranged from 0.68 to 1.05; in URTI, from 0.70 to 1.22.

Conclusions

CV events were more likely after LRTI than after URTI. When analysed by specific indication, CV risk associated with clarithromycin was no different to other antibiotics.



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Do perceived job insecurity and annoyance due to air and noise pollution predict incident self-rated poor health? A prospective analysis of independent and joint associations using a German national representative cohort study

Background

Current economic and social change has contributed to increasing job insecurity and traffic-related pollution in residential areas. Both job insecurity and exposure to noise and air pollution are known determinants of population health and can concur in peoples' lives. This may hold true particularly for socially disadvantaged subpopulations. Nevertheless, the potential independent and joint links of those exposures to health have been rarely examined so far. We aimed to contribute to the scarce body of evidence.

Methods

Information on perceived job insecurity and exposures to noise and air pollution as expressed by annoyance as well as on self-rated health were gathered from 2 waves of the population-based German Socio-Economic Panel (2009 and 2011, N=6544). We performed multivariable Poisson regression to examine the independent and joint risk of poor health in 2011 by perceived job insecurity and annoyance due to noise and air pollution in 2009.

Results

After the 2-year follow-up in 2011, 571 (8.7%) participants rated their health as poor. The risk of reporting incident poor health was increased by roughly 40% in employees reporting high versus low perceived job insecurity and annoyance due to noise and air pollution, respectively. This risk increased when both exposures were present at higher levels (risk ratio=1.95 (1.49 to 2.55)).

Conclusions

Work-related and environmental exposures may accumulate and have a joint health impact. Elaboration on the link between occupational and residential exposures is warranted in the light of their concurrence and their implications for health inequities.



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E-therapies in England for stress, anxiety or depression: what is being used in the NHS? A survey of mental health services

Objective

To document the range of web and smartphone apps used and recommended for stress, anxiety or depression by the National Health Service (NHS) in England.

Design

The study was conducted using Freedom of Information (FOI) requests and systematic website searches.

Data sources

Data were collected via FOI requests to NHS services between 13 February 2015 and 31 March 2015, and searches conducted on NHS apps library websites between 26 March 2015 and 2 November 2015.

Data collection/extraction methods

Data were compiled from responses to: (1) FOI requests sent to all Improving Access to Psychological Therapies (IAPT) services and NHS Mental Health Trusts in England and (2) NHS apps library search results.

Results

A total of 61 (54.95%) out of the then 111 IAPT service providers responded, accounting for 191 IAPT services, and all 51 of the then NHS Mental Health Trusts responded. The results were that 13 different web apps and 35 different smartphone apps for depression, anxiety or stress were available through either referral services or the online NHS Apps Libraries. The apps used and recommended vary by area and by point of access (online library/IAPT/trust).

Conclusions

Future research is required to establish the evidence base for the apps that are being used in the NHS in England. There is a need for service provision to be based on evidence and established guidelines.



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Clinical efficacy of {beta}-lactam/{beta}-lactamase inhibitor combinations for the treatment of bloodstream infection due to extended-spectrum {beta}-lactamase-producing Enterobacteriaceae in haematological patients with neutropaenia: a study protocol for a retrospective observational study (BICAR)

Introduction

Bloodstream infection (BSI) due to extended-spectrum β-lactamase-producing Gram-negative bacilli (ESBL-GNB) is increasing at an alarming pace worldwide. Although β-lactam/β-lactamase inhibitor (BLBLI) combinations have been suggested as an alternative to carbapenems for the treatment of BSI due to these resistant organisms in the general population, their usefulness for the treatment of BSI due to ESBL-GNB in haematological patients with neutropaenia is yet to be elucidated. The aim of the BICAR study is to compare the efficacy of BLBLI combinations with that of carbapenems for the treatment of BSI due to an ESBL-GNB in this population.

Methods and analysis

A multinational, multicentre, observational retrospective study. Episodes of BSI due to ESBL-GNB occurring in haematological patients and haematopoietic stem cell transplant recipients with neutropaenia from 1 January 2006 to 31 March 2015 will be analysed. The primary end point will be case-fatality rate within 30 days of onset of BSI. The secondary end points will be 7-day and 14-day case-fatality rates, microbiological failure, colonisation/infection by resistant bacteria, superinfection, intensive care unit admission and development of adverse events.

Sample size

The number of expected episodes of BSI due to ESBL-GNB in the participant centres will be 260 with a ratio of control to experimental participants of 2.

Ethics and dissemination

The protocol of the study was approved at the first site by the Research Ethics Committee (REC) of Hospital Universitari de Bellvitge. Approval will be also sought from all relevant RECs. Any formal presentation or publication of data from this study will be considered as a joint publication by the participating investigators and will follow the recommendations of the International Committee of Medical Journal Editors (ICMJE). The study has been endorsed by the European Study Group for Bloodstream Infection and Sepsis (ESGBIS) and the European Study Group for Infections in Compromised Hosts (ESGICH).



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Myocardial infarction in the Wisconsin Longitudinal Study: the interaction among environmental, health, social, behavioural and genetic factors

Objectives

This study examined how environmental, health, social, behavioural and genetic factors interact to contribute to myocardial infarction (MI) risk.

Design

Survey data collected by Wisconsin Longitudinal Study (WLS), USA, from 1957 to 2011, including 235 environmental, health, social and behavioural factors, and 77 single- nucleotide polymorphisms were analysed for association with MI. To identify associations with MI we utilized recursive partitioning and random forest prior to logistic regression and chi-squared analyses.

Participants

6198 WLS participants (2938 men; 3260 women) who (1) had a MI before 72 years and (2) had a MI between 65 and 72 years.

Results

In men, stroke (LR OR: 5.01, 95% CI 3.36 to 7.48), high cholesterol (3.29, 2.59 to 4.18), diabetes (3.24, 2.53 to 4.15) and high blood pressure (2.39, 1.92 to 2.96) were significantly associated with MI up to 72 years of age. For those with high cholesterol, the interaction of smoking and lower alcohol consumption increased prevalence from 23% to 41%, with exposure to dangerous working conditions, a factor not previously linked with MI, further increasing prevalence to 50%. Conversely, MI was reported in <2.5% of men with normal cholesterol and no history of diabetes or depression. Only stroke (4.08, 2.17 to 7.65) and diabetes (2.71, 1.81 to 4.04) by 65 remained significantly associated with MI for men after age 65. For women, diabetes (5.62, 4.08 to 7.75), high blood pressure (3.21, 2.34 to 4.39), high cholesterol (2.03, 1.38 to 3.00) and dissatisfaction with their financial situation (4.00, 1.94 to 8.27) were significantly associated with MI up to 72 years of age. Conversely, often engaging in physical activity alone (0.53, 0.32 to 0.89) or with others (0.34, 0.21 to 0.57) was associated with the largest reduction in odds of MI. Being non-diabetic with normal blood pressure and engaging in physical activity often lowered prevalence of MI to 0.2%. Only diabetes by 65 (4.25, 2.50 to 7.24) and being exposed to dangerous work conditions at 54 (2.24, 1.36 to 3.69) remained significantly associated with MI for women after age 65, while still menstruating at 54 (0.46, 0.23 to 0.91) was associated with reduced odds of MI.

Conclusions

Together these results indicate important differences in factors associated with MI between the sexes, that combinations of factors greatly influence the likelihood of MI, that MI-associated factors change and associations weaken after 65 years of age in both sexes, and that the limited genotypes assessed were secondary to environmental, health, social and behavioral factors.



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Correction

Hanaki N, Yamashita K, Kunisawa S, et al. Effect of the number of request calls on the time from call to hospital arrival: a cross-sectional study of an ambulance record database in Nara prefecture, Japan. BMJ Open 2016;6:e012194.

The baseline patient characteristics were compared using analysis of variance (ANOVA), not the Kruskal–Wallis test. Therefore the corrected Table 1 footnote should read:

*P-value by ANOVA

P-value by Student's t-test

SD: standard deviation, Qu: quartile, ACS: acute coronary syndromes, CPA: Cardiopulmonary arrest,

DOC: disturbance of consciousness, request call: request call to hospital for transportation

The detailed information about each area are not available for disclosing, because of data sharing policy.

In table 3 the column header "Time from call to hospital arrival" should read "Time for request call". The corrected Table 3 is shown below.

Table 3

The number and the time for request call categorized...



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Lymphoepithelial Sialadenitis Involving HIV-Infected and Sjogren Syndrome Patients: A Cytologic Study

Abstract

Lymphoepithelial salivary gland cysts are rarely seen in autoimmune diseases particularly Sjogren syndrome as well as in HIV for which medical management is advocated. To study the morphology of these cysts, correlate with the disease process and assess the final outcome. Case series. Fine needle aspiration clinic. HIV-infected and autoimmune disease patients with lymphoepithelial cysts. Antiretroviral therapy for HIV-patients and anti-inflammatory drugs for Sjogren syndrome. Three HIV-infected patients (two children and one adult) and three middle aged female patients presented with parotid and submandibular cysts, two of which were bilateral along with submandibular (one each in the HIV and the autoimmune group). In the adult HIV-patient, the cyst was found at the inception of the disease while the other pediatric HIV-patients just crossed a decade. Of the other three cases of Sjogren syndrome, two were primary and one, secondary to rheumatoid arthritis. All the cysts regressed completely with treatment of the respective diseases which was confirmed by ultrasonograms. Lymphoepithelial cysts are produced by release of serous secretion by the acinar and ductal cells within the epithelial islands in the process of their destruction. Possibly, antibody mediated increased secretion in the initial stages also plays a role. Lymphoepithelial cysts of HIV patients may occur in the course of treatment, not necessarily in the beginning, though it resolves spontaneously. Lymphoepithelial cysts of primary or secondary Sjogren syndrome may be repressed sufficiently by anti-inflammatory/immunosuppressant treatment.



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Smoking restrictions head to hearing - Seacoastonline.com


Smoking restrictions head to hearing
Seacoastonline.com
Secondhand smoke causes nearly 42,000 deaths, including more than 7,000 lung cancer deaths among nonsmoking adults each year in the United States. Adult cancers linked to secondhand smoke include cancer of the lung, larynx, pharynx, bladder, breast ...

and more »


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Cancer : un larynx artificiel pour sentir et parler à nouveau - L'indépendant.fr


Cancer : un larynx artificiel pour sentir et parler à nouveau
L'indépendant.fr
L'équipe de Christian Debry*, chef du service ORL et chirurgie cervico-faciale au CHU de Strasbourg, a ainsi développé pour ces patients un larynx artificiel. Depuis 2012, six personnes ont été implantées. Problème, ils n'ont pu conserver l'implant en ...



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Anesthetic considerations for patients with esophageal achalasia undergoing peroral endoscopic myotomy: a retrospective case series review

Abstract

Purpose

Peroral endoscopic myotomy (POEM) is a novel technique for treating esophageal achalasia. During POEM, carbon dioxide (CO2) is insufflated to aid surgical dissection, but it may inadvertently track into surrounding tissues, causing systemic CO2 uptake and tension capnoperitoneum. This in turn may affect cardiorespiratory function. This study quantified these cardiorespiratory effects and treatment by hyperventilation and percutaneous abdominal needle decompression (PND).

Methods

One hundred and seventy-three consecutive patients who underwent POEM were included in this four-year retrospective study. Procedure-related changes in peak inspiratory pressure (pmax), end-tidal CO2 levels (etCO2), minute ventilation (MV), mean arterial pressure (MAP), and heart rate (HR) were analyzed. We also quantified the impact of PND on these cardiorespiratory parameters.

Results

During the endoscopic procedure, cardiorespiratory parameters increased from baseline: pmax 15.1 (4.5) vs 19.8 (4.7) cm H2O; etCO2 4.5 (0.4) vs 5.5 (0.9) kPa [34.0 (2.9) vs 41.6 (6.9) mmHg]; MAP 73.9 (9.7) vs 99.3 (15.2) mmHg; HR 67.6 (12.4) vs 85.3 (16.4) min−1 (P < 0.001 for each). Hyperventilation [MV 5.9 (1.2) vs 9.0 (1.8) L·min−1, P < 0.001] was applied to counteract iatrogenic hypercapnia. Individuals with tension capnoperitoneum treated with PND (n = 55) had higher peak pmax values [22.8 (5.7) vs 18.4 (3.3) cm H2O, P < 0.001] than patients who did not require PND. After PND, pmax [22.8 (5.7) vs 19.9 (4.3) cm H2O, P = 0.045] and MAP [98.2 (16.3) vs 88.6 (11.8) mmHg, P = 0.013] decreased. Adverse events included pneumothorax (n = 1), transient myocardial ischemia (n = 1), and subcutaneous emphysema (n = 49). The latter precluded immediate extubation in eight cases. Postanesthesia care unit (PACU) stay was longer in individuals with subcutaneous emphysema than in those without [74.9 min (34.5) vs 61.5 (26.8 min), P = 0.007].

Conclusion

Carbon dioxide insufflation during POEM produces systemic CO2 uptake and increased intra-abdominal pressure. Changes in cardiorespiratory parameters include increased pmax, etCO2, MAP, and HR. Hyperventilation and PND help mitigate some of these changes. Subcutaneous emphysema is common and may delay extubation and prolong PACU stay.



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Dr. Seiwert on Next Steps in Treatment of Patients With Head and Neck Cancer - OncLive


OncLive

Dr. Seiwert on Next Steps in Treatment of Patients With Head and Neck Cancer
OncLive
Tanguy I. Seiwert, MD, assistant professor of Medicine, University of Chicago Medicine, discusses the next steps researchers are taking to improve survival outcomes for patients with head and neck cancer. While there are the 2 FDA approvals of the PD-1 ...

and more »


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Men get thyroid disease, too - FOX 5 Atlanta


FOX 5 Atlanta

Men get thyroid disease, too
FOX 5 Atlanta
"He's been doing my hair for about 11 years now," says Tawanda Thompson. As they got to know each other, Tawanda Thompson shared her story of being a two-time thyroid cancer survivor. "I always kind of joke with him that I was 'patient zero.' So, when ...



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Œsophagite disséquante : à propos de deux observations



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Insights from Global Analyses of Long Noncoding RNAs in Breast Cancer

Abstract

Purpose of Review

The goal of this review was to compare and contrast the results and implications from several recent transcriptomic studies that analyzed the expression of long noncoding RNAs (lncRNAs) in breast cancer. How many lncRNAs are dysregulated in breast cancer? Do dysregulated lncRNAs contribute to breast cancer etiology? Are lncRNAs viable biomarkers in breast cancer?

Recent Findings

Transcriptomic profiling of breast cancer tissues, mostly from The Cancer Genome Atlas, identified thousands of long noncoding RNAs that are expressed and dysregulated in breast cancer. The expression of lncRNAs alone can divide patients into molecular subtypes. Subsequent functional studies demonstrated that several of these lncRNAs have important roles in breast cancer cell biology.

Summary

Thousands of lncRNAs are dysregulated in breast cancer that can be developed as biomarkers for prognostic or therapeutic purposes. The reviewed reports provide a roadmap to guide functional studies to discover lncRNAs with critical biological functions relating to breast cancer development and progression.



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Towards better antimicrobial susceptibility testing: impact of the Journal of Antimicrobial Chemotherapy

<span class="paragraphSection">Susceptibility testing of bacteria is one of the most important tests performed in a clinical microbiology laboratory. Improvements in laboratory techniques, especially the move towards standardized susceptibility testing, has provided better consistency and accuracy of testing. When used in conjunction with the most recently developed interpretative criteria, the result is better prediction of the outcome of antimicrobial therapy for infected patients. Throughout the last four decades this Journal has published numerous articles evidencing improvements and new techniques, a valuable source of information for microbiology laboratories.</span>

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Retrospective analysis of genome sequences revealed the wide dissemination of optrA in Gram-positive bacteria

<span class="paragraphSection">Sir,</span>

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Comment on: Benchmarking of methods for identification of antimicrobial resistance genes in bacterial whole genome data

<span class="paragraphSection">Sir,</span>

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Genomic islands 1 and 2 carry multiple antibiotic resistance genes in Pseudomonas aeruginosa ST235, ST253, ST111 and ST175 and are globally dispersed

<span class="paragraphSection">Sir,</span>

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Development of operationalized intravenous to oral antibiotic switch criteria

<span class="paragraphSection"><strong>Objectives:</strong> Despite huge overlap in suggested criteria for a safe intravenous (iv)-to-oral antibiotic switch, there is considerable variation in their operationalization. The objective of this study was to develop a set of measurable conditions that should be met in adult hospitalized patients for a safe iv-to-oral switch.<strong>Methods:</strong> A RAND-modified Delphi procedure was performed to develop a set of operationalized iv-to-oral switch criteria. Switch criteria and their accompanying suggested measurable conditions were extracted from the literature and appraised by a multidisciplinary expert panel during two questionnaire rounds with a face-to-face meeting between these two rounds. In a final step, the experts could approve the set of developed operationalized switch criteria.<strong>Results:</strong> Seven switch criteria and 41 accompanying measurable conditions extracted from the literature were appraised. Sixteen measurable conditions that operationalize six switch criteria were selected: (i) stable systolic blood pressure; and the absence of (ii) fever, (iii) temperature <36°C, (iv) malabsorption syndrome, (v) short bowel syndrome, (vi) severe gastroparesis, (vii) ileus, (viii) continuous nasogastric suction, (ix) vomiting, (x) (severe) sepsis, (xi) fasciitis necroticans, (xii) CNS infection, (xiii) <span style="font-style:italic;">Staphylococcus aureus</span> bacteraemia, and (xiv) endovascular infection. In addition, (xv) the patient should be cooperative and (xvi) adequate antimicrobial concentration should be achievable at the site of infection by oral administration.<strong>Conclusions:</strong> These operationalized criteria can be used in daily clinical practice. Future use of these criteria in audits and as rules in clinical decision support systems will facilitate the performance and evaluation of iv–oral switch programmes.</span>

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Prolonged use of tedizolid in a pulmonary non-tuberculous mycobacterial infection after linezolid-induced toxicity

<span class="paragraphSection">Sir,</span>

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Intrinsic rifamycin resistance of Mycobacterium abscessus is mediated by ADP-ribosyltransferase MAB_0591

<span class="paragraphSection"><strong>Objectives:</strong> Rifampicin, a potent first-line TB drug of the rifamycin group, shows only little activity against the emerging pathogen <span style="font-style:italic;">Mycobacterium abscessus.</span> Reportedly, bacterial resistance to rifampicin is associated with polymorphisms in the target gene <span style="font-style:italic;">rpoB</span> or the presence of enzymes that modify and thereby inactivate rifampicin. The aim of this study was to investigate the role of the <span style="font-style:italic;">MAB_0591</span> (<span style="font-style:italic;">arrMab</span>)-encoded rifampicin ADP-ribosyltransferase (Arr_<span style="font-style:italic;">Mab</span>) in innate high-level rifampicin resistance in <span style="font-style:italic;">M. abscessus.</span><strong>Methods:</strong> Recombinant <span style="font-style:italic;">Escherichia coli</span> and <span style="font-style:italic;">Mycobacterium tuberculosis</span> strains expressing <span style="font-style:italic;">MAB_0591</span> were generated, as was an <span style="font-style:italic;">M. abscessus</span> deletion mutant deficient for <span style="font-style:italic;">MAB_0591.</span> MIC assays were used to study susceptibility to rifampicin and C25 carbamate-modified rifamycin derivatives.<strong>Results:</strong> Heterologous expression of <span style="font-style:italic;">MAB_0591</span> conferred rifampicin resistance to <span style="font-style:italic;">E. coli</span> and <span style="font-style:italic;">M. tuberculosis</span>. Rifamycin MIC values were consistently lower for the <span style="font-style:italic;">M. abscessus</span> Δ<span style="font-style:italic;">arrMab</span> mutant as compared with the <span style="font-style:italic;">M. abscessus</span> ATCC 19977 parental type strain. The rifamycin WT phenotype was restored after complementation of the <span style="font-style:italic;">M. abscessus</span> Δ<span style="font-style:italic;">arrMab</span> mutant with <span style="font-style:italic;">arrMab</span>. Further MIC data demonstrated that a C25 modification increases rifamycin activity in WT <span style="font-style:italic;">M. abscessus</span>. However, MIC studies in the <span style="font-style:italic;">M. abscessus</span> Δ<span style="font-style:italic;">arrMab</span> mutant suggest that C25 modified rifamycins are still subject to modification by Arr_<span style="font-style:italic;">Mab</span>.<strong>Conclusions:</strong> Our findings identify Arr_<span style="font-style:italic;">Mab</span> as the major innate rifamycin resistance determinant of <span style="font-style:italic;">M. abscessus.</span> Our data also indicate that Arr_<span style="font-style:italic;">Mab</span>-mediated rifamycin resistance in <span style="font-style:italic;">M. abscessus</span> can only in part be overcome by C25 carbamate modification.</span>

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HIV-1 diagnosis with unquantifiable viraemia: don’t be naive, look for antiretroviral drugs

<span class="paragraphSection">Sir,</span>

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Relationship between vancomycin tolerance and clinical outcomes in Staphylococcus aureus bacteraemia

<span class="paragraphSection"><strong>Background:</strong> Previous data have demonstrated the clinical importance of vancomycin MIC values in <span style="font-style:italic;">Staphylococcus aureus</span> bacteraemia (SAB); however, the impact of vancomycin tolerance (VT) is unknown.<strong>Objectives:</strong> To compare the frequency of clinical failure between patients with VT and non-VT isolates in SAB.<strong>Methods:</strong> This was a retrospective cohort study of patients with SAB, excluding treatment <48 h or polymicrobial bacteraemia. The primary outcome was clinical failure (composite of 30 day mortality, non-resolving signs and symptoms, and 60 day recurrence). Vancomycin MIC and MBC were determined by broth microdilution. The association between VT (MBC/MIC ≥32) and clinical failure was evaluated by multivariable Poisson regression.<strong>Results:</strong> Of the 225 patients, 26.7% had VT isolates. VT was associated with clinical failure (48.0% overall) in unadjusted analysis [68.3% (<span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>41/60) versus 40.6% (<span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>67/165); <span style="font-style:italic;">P </span><<span style="font-style:italic;"> </span>0.001] and this relationship persisted in multivariable analysis (adjusted risk ratio, 1.74; 95% CI, 1.36-2.24; <span style="font-style:italic;">P </span><<span style="font-style:italic;"> </span>0.001). The association between VT and clinical failure was also consistent within strata of methicillin susceptibility [methicillin susceptible (<span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>125, risk ratio, 1.67; 95% CI, 1.20-2.32; <span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.002); methicillin resistant (<span style="font-style:italic;">n </span>=<span style="font-style:italic;"> </span>100, risk ratio, 1.69; 95% CI, 1.14-2.51; <span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.010)]. Among methicillin-susceptible SAB cases treated with β-lactam therapy, VT remained associated with clinical failure (risk ratio, 1.77; 95% CI, 1.19-2.61; <span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.004).<strong>Conclusions:</strong> VT was associated with clinical failure in SAB, irrespective of methicillin susceptibility or definitive treatment. VT may decrease the effectiveness of cell-wall-active therapy or be a surrogate marker of some other pathogen-specific factor associated with poor outcomes. Future research should evaluate if bactericidal non-cell-wall-active agents improve outcomes in VT SAB.</span>

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Gut-sparing treatment of urinary tract infection in patients at high risk of Clostridium difficile infection

<span class="paragraphSection"><strong>Background:</strong> Recipients of faecal microbiota transplantation (FMT) in treatment of recurrent <span style="font-style:italic;">Clostridium difficile</span> infection (RCDI) remain at markedly increased risk of re-infection with <span style="font-style:italic;">C. difficile</span> with new antibiotic provocations. Urinary tract infections (UTIs) are common indications for antibiotics in these patients, often resulting in <span style="font-style:italic;">C. difficile</span> re-infection.<strong>Methods:</strong> We present a case series of 19 patients treated with parenteral aminoglycosides for UTI following FMT for RCDI. A 3 day outpatient regimen of once-daily intramuscular administration of gentamicin was used to treat 18 consecutive FMT recipients with uncomplicated UTI. One other patient was treated for a complicated UTI with intravenous amikacin. Profiling of 16S rRNA genes was used to track changes in faecal microbial community structure during this regimen in three patients.<strong>Results:</strong> The protocol was highly effective in treating UTI symptoms. None of the patients suffered a re-infection with <span style="font-style:italic;">C. difficile</span>. The faecal microbial communities remained undisturbed by treatment with intramuscular administration of gentamicin.<strong>Conclusions:</strong> Despite falling out of favour in recent years, aminoglycoside antibiotics given parenterally have the advantage of minimal penetration into the gut lumen. A brief (3 day) course of parenteral gentamicin was safe and effective in curing UTI in patients at high risk of <span style="font-style:italic;">C. difficile</span> infection without perturbing their gut microbiota.</span>

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Genotypic susceptibility score (GSS) and CD4+ T cell recovery in HIV-1 patients with suppressed viral load

<span class="paragraphSection"><strong>Objectives:</strong> HIV drug resistance, measured by the genotypic susceptibility score (GSS), has a deleterious effect on the virological outcome of HIV-1-infected patients. However, it is not known if GSS retains any predictive value for CD4 recovery in patients with suppressed viral load. <strong>Methods:</strong> Four hundred and six patients on virological failure (>500 copies/mL) with GSS<strong> </strong><6 months prior to switch therapy who achieved undetectable plasma viral load (<50 copies/mL) within 1 year, remained undetectable >1 year on an unchanged regimen and had CD4 data available during entire follow-up were included. Adjusted and unadjusted analyses of all characteristics at switch related to CD4 recovery were made for three time frames: (i) ‘switch–suppression’; (ii) ‘suppression–1 year’; and (iii) ‘switch–1 year’.<strong>Results:</strong> Higher GSS was associated with a greater CD4 recovery between ‘switch’ and ‘1 year’ in the unadjusted analysis (<span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.010); however, the effect of GSS was no longer statistically significant after adjusting for pre-switch clinical (CD4 count and plasma viral load) and demographic variables. Furthermore, only a lower pre-switch CD4 count was associated with increased CD4 recovery in the ‘suppression–1 year’ period in both unadjusted and adjusted models. The main CD4 recovery occurred in ‘switch–suppression’ and the variables associated, both unadjusted and adjusted, were CD4 and plasma viral load at switch, maintaining a trend for GSS (<span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.06).<strong>Conclusions:</strong> In individuals who re-suppressed HIV viraemia after switching therapy, regimens having a higher GSS were associated with improved CD4 recovery only during the period from switch to virological suppression, but, once viral load is re-suppressed, the GSS of the new regimen has no further effect on subsequent CD4 recovery.</span>

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Alarming increase in pretreatment HIV drug resistance in children living in sub-Saharan Africa: a systematic review and meta-analysis

<span class="paragraphSection"><strong>Background:</strong> Children have an augmented risk of pretreatment HIV drug resistance (PDR) due to exposure to antiretroviral drugs for the prevention of mother-to-child transmission (PMTCT). Paediatric data are essential to evaluate the effectiveness of the restricted number of paediatric regimens currently available, but these data are scarce.<strong>Methods:</strong> We conducted a systematic review of the literature on PDR in children (median age ≤12 years) in sub-Saharan Africa. We separately extracted the proportion of children with PDR for children with and without prior PMTCT exposure, used random-effects meta-analysis to pool proportions and used meta-regression to assess subgroup differences.<strong>Results:</strong> We included 19 studies representing 2617 children from 13 countries. The pooled PDR prevalence was 42.7% (95% CI 26.2%–59.1%) among PMTCT-exposed children and 12.7% (95% CI 6.7%–18.7%) among PMTCT-unexposed children (<span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.004). The PDR prevalence in PMTCT-unexposed children increased from 0% in 2004 to 26.8% in 2013 (<span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.009). NNRTI mutations were detected in 32.4% (95% CI 18.7%–46.1%) of PMTCT-exposed children and in 9.7% (95% CI 4.6%–14.8%) of PMTCT-unexposed children; PI mutations were uncommon (<2.5%). PDR was more common in children aged <3 years compared with children aged ≥3 years [40.9% (95% CI 27.6%–54.3%) versus 17.6% (95% CI 8.9%–26.3%), respectively (<span style="font-style:italic;">P </span>=<span style="font-style:italic;"> </span>0.025)].<strong>Conclusions:</strong> The PDR prevalence in African children is high and rapidly increasing. Even in PMTCT-unexposed children, the most recent reports indicate that PDR is present in up to a third of children starting first-line therapy. Our data underscore the importance of initiating PI-based first-line ART in young children (<3 years of age) and suggest that older children may also benefit from this approach.</span>

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Linezolid: a promising option in the treatment of Gram-positives

<span class="paragraphSection">Linezolid, an oxazolidinone antimicrobial agent that acts by inhibiting protein synthesis in a unique fashion, is used in the treatment of community-acquired pneumonia, skin and soft-tissue infections and other infections caused by Gram-positive bacteria including VRE and methicillin-resistant staphylococci. Currently, linezolid resistance among these pathogens remains low, commonly <1.0%, although the prevalence of antibiotic resistance is increasing in many countries. Therefore, the development of resistance by clinical isolates should prompt increased attention of clinical laboratories to routinely perform linezolid susceptibility testing for this important agent and should be taken into account when considering its therapeutic use. Considering the importance of linezolid in the treatment of infections caused by Gram-positive bacteria, this review was undertaken to optimize the clinical use of this antibiotic.</span>

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In vitro activity of gentamicin as an adjunct to penicillin against biofilm group B Streptococcus

<span class="paragraphSection"><strong>Objectives:</strong> Group B <span style="font-style:italic;">Streptococcus</span> (GBS) increasingly causes invasive disease in non-pregnant adults, particularly in elderly persons and those with underlying diseases. Combination therapy with penicillin plus gentamicin has been suggested for periprosthetic joint infection. The postulated synergism of this combination is based on experiments with planktonic bacteria. We aimed to assess the efficacy of this combination against sessile bacteria.<strong>Methods:</strong> Four different GBS strains were used. We compared results of MICs with those of minimal biofilm eradication concentrations (MBECs), applied chequerboard assays to the MBEC device and calculated the fractional inhibitory concentration index. Synergism was evaluated with time–kill assays against bacteria adherent to cement beads, using penicillin (0.048, 0.2 and 3 mg/L), gentamicin (4 and 12.5 mg/L) and a combination thereof. Results were evaluated via colony counting after sonication of beads and scanning electron microscopy.<strong>Results:</strong> MBEC/MIC ratios were 2000–4000 for penicillin and 1–4 for gentamicin. In chequerboard assays, synergism was observed in all four isolates. In time–kill assays, penicillin and 12.5 mg/L gentamicin showed synergism in two isolates. In the other two isolates 12.5 mg/L gentamicin alone was as efficient as the combination therapy.<strong>Conclusions:</strong> These <span style="font-style:italic;">in vitro</span> investigations show activity of 12.5 mg/L gentamicin, alone or as an adjunct to penicillin, against four strains of biofilm GBS. This concentration cannot be achieved in bone with systemic administration, but can be reached if administered locally. The combination of systemic penicillin plus local gentamicin indicates a potential application in orthopaedic-device-associated GBS infections. Studies with a larger number of strains are required to confirm our results.</span>

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Pharmacological inhibition of p110δ subunit of PI3K confers protection against experimental leishmaniasis

<span class="paragraphSection"><strong>Objectives:</strong> This study aimed to evaluate the immuno-prophylactic and -therapeutic effect of p110δ-specific pharmacological inhibitors (CAL-101 and IC87114), either alone or in combination with amphotericin B, against experimental cutaneous leishmaniasis (CL) and visceral leishmaniasis (VL).<strong>Methods:</strong> Female BALB/c mice were infected intravenously with <span style="font-style:italic;">Leishmania donovani</span> or subcutaneously with <span style="font-style:italic;">Leishmania major</span>. Prophylactic treatment was initiated 24 h prior to infection, whereas therapeutic treatments with or without amphotericin B were initiated either 1 week or 2 weeks post-infection. At different times post-infection, mice were sacrificed and parasite burden, regulatory T cell (Treg) numbers and cytokine production were assessed in the liver, spleen, draining lymph nodes and footpads. In addition, direct cytolytic effects of the inhibitors on parasite growth in axenic cultures and inside infected and uninfected macrophages were also assessed.<strong>Results:</strong> Prophylactic and therapeutic administration of p110δ pharmacological inhibitors significantly reduced cutaneous lesion (in CL) and parasite burdens (in VL and CL) in the spleens, livers and footpads of infected mice. The reduction in parasite burden was associated with a concomitant reduction in Treg numbers and cytokine production by liver, spleen and lymph node cells. Combined low-dose CAL-101 and amphotericin B therapy caused complete clearance of parasites in mice infected with <span style="font-style:italic;">L. donovani</span>.<strong>Conclusions:</strong> Our studies clearly show a novel therapeutic option for leishmaniasis based on CAL-101 monotherapy or CAL-101 and amphotericin B combination therapy. These observations have important and direct implications for antimicrobial immunotherapy and drug/vaccine development against leishmaniasis.</span>

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Synergistic activity of fosfomycin, β-lactams and peptidoglycan recycling inhibition against Pseudomonas aeruginosa

<span class="paragraphSection"><strong>Objectives:</strong> To evaluate the interconnection between peptidoglycan (PG) recycling, fosfomycin susceptibility and synergy between fosfomycin and β-lactams in <span style="font-style:italic;">Pseudomonas aeruginosa</span>.<strong>Methods:</strong> Fosfomycin MICs were determined by broth microdilution and Etest for a panel of 47 PAO1 mutants defective in several components of PG recycling and/or AmpC induction pathways. PAO1 fosfomycin MICs were also determined in the presence of a 5 mM concentration of the NagZ inhibitor PUGNAc. Population analysis of fosfomycin susceptibility and characterization of the resistant mutants that emerged was also performed for selected strains. Finally, fosfomycin, imipenem and fosfomycin + imipenem killing curves were assessed.<strong>Results:</strong> Mutants defective in AmpG, NagZ or all three AmpD amidases showed a marked increase in fosfomycin susceptibility (at least two 2-fold dilutions with respect to WT PAO1). Moreover, PAO1 fosfomycin MICs were consistently reduced from 48 to 24 mg/L in the presence of a 5 mM concentration of PUGNAc. Fosfomycin hypersusceptibility of the <span style="font-style:italic;">ampG</span>, <span style="font-style:italic;">nagZ</span> and triple <span style="font-style:italic;">ampD</span> mutants was also clearly confirmed in the performed population analysis, although the emergence of resistant mutants, through GlpT mutations, was not avoided. Synergy between fosfomycin and imipenem was evidenced for the WT strain, the AmpC-hyperproducing strain (triple AmpD mutant) and the NagZ and AmpG mutants in killing curves. Moreover, regrowth of resistant mutants was not evidenced for the combination.<strong>Conclusions:</strong> PG recycling inhibitors are envisaged as useful adjuvants in the treatment of <span style="font-style:italic;">P. aeruginosa</span> infections with β-lactams and fosfomycin and therefore further development of these molecules is encouraged.</span>

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Acute reversible pancreatitis induced by posaconazole

<span class="paragraphSection">Sir,</span>

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Variability in antibiotic use across Ontario acute care hospitals

<span class="paragraphSection"><strong>Background:</strong> Antibiotic stewardship is a required organizational practice for Canadian acute care hospitals, yet data are scarce regarding the quantity and composition of antibiotic use across facilities. We sought to examine the variability, and risk-adjusted variability, in antibiotic use across acute care hospitals in Ontario, Canada’s most populous province.<strong>Methods:</strong> Antibiotic purchasing data from IMS Health, previously demonstrated to correlate strongly with internal antibiotic dispensing data, were acquired for 129 Ontario hospitals from January to December 2014 and linked to patient day (PD) denominator data from administrative datasets. Hospital variation in DDDs/1000 PDs was determined for overall antibiotic use, class-specific use and six practices of clinical or ecological significance. Multivariable risk adjustment for hospital and patient characteristics was used to compare observed versus expected utilization.<strong>Results:</strong> There was 7.4-fold variability in the quantity of antibiotic use across the 129 acute care hospitals, from 253 to 1873 DDDs/1000 PDs. Variation was evident within hospital subtypes, exceeded that explained by hospital and patient characteristics, and included wide variability in proportion of broad-spectrum antibiotics (IQR 36%–48%), proportion of fluoroquinolones among respiratory antibiotics (IQR 40%–62%), proportion of ciprofloxacin among urinary anti-infectives (IQR 44%–60%), proportion of antibiotics with highest risk for <span style="font-style:italic;">Clostridium difficile</span> (IQR 29%–40%), proportion of ‘reserved-use’ antibiotics (IQR 0.8%–3.5%) and proportion of anti-pseudomonal antibiotics among antibiotics with Gram-negative coverage (IQR 26%–40%).<strong>Conclusions:</strong> There is extensive variability in antibiotic use, and risk-adjusted use, across acute care hospitals. This could motivate, focus and benchmark antibiotic stewardship efforts.</span>

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Comparative in vitro activity of oritavancin and other agents against vancomycin-susceptible and -resistant enterococci

<span class="paragraphSection">Sir,</span>

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Lack of adherence to SHEA-IDSA treatment guidelines for Clostridium difficile infection is associated with increased mortality

<span class="paragraphSection"><div class="boxTitle">Objectives</div>The objective of this study was to determine our institution's compliance with 2010 Society for Healthcare Epidemiology of America and IDSA <span style="font-style:italic;">Clostridium difficile</span> infection (CDI) treatment guidelines and their respective outcomes<span style="font-style:italic;">.</span><div class="boxTitle">Methods</div>We collected clinical parameters, laboratory values, antibiotic therapy and clinical outcomes from the electronic medical records for all patients hospitalized at our institution with a diagnosis of CDI from December 2012 to November 2013. We specifically evaluated whether SHEA-IDSA treatment guidelines were followed and evaluated the associations between guideline adherence and severe outcomes including mortality.<div class="boxTitle">Results</div>We identified 230 patients with CDI meeting inclusion criteria during the study period. Of these, 124 (54%) were appropriately treated, 46 (20%) were under-treated and 60 (26%) were over-treated. All-cause 90 day mortality was 17.4% overall; 43.5% in the under-treated group versus 12.9% in those appropriately treated (<span style="font-style:italic;">P</span> < 0.0001) and 10.9% in those appropriately treated plus over-treated (<span style="font-style:italic;">P</span> < 0.0001). Similarly, 90 day mortality attributed to CDI was 21.7% in those under-treated versus 8.9% in those appropriately treated (<span style="font-style:italic;">P</span> = 0.03) and 8.2% in those either appropriately treated or over-treated (<span style="font-style:italic;">P</span> = 0.015). Severe-complicated CDI occurred in 46 patients. In this subgroup, there was a non-significant trend towards increased mortality in under-treated patients (56.7%) compared with appropriately treated patients (37.5%, <span style="font-style:italic;">P</span> = 0.35). Under-treatment was also associated with a higher rate of CDI-related ICU transfer (17.4% versus 4.8% in those appropriately treated, <span style="font-style:italic;">P</span> = 0.023).<div class="boxTitle">Conclusions</div>Adherence to CDI treatment guidelines is associated with improved outcomes especially in those with severe disease. Increased emphasis on provision of appropriate, guideline-based CDI treatment appears warranted.</span>

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Antibiofilm effects of topical corticosteroids and intranasal saline in patients with chronic rhinosinusitis with nasal polyps depend on bacterial species and their biofilm-forming capacity

Abstract

Microbial biofilms have been implicated in the pathogenesis of chronic rhinosinusitis with nasal polyposis (CRSwNP). Intranasal application of corticosteroids and saline is a reliable option for their management. The aim of our study was to evaluate in vitro antibiofilm effects of corticosteroids and isotonic and hypertonic nasal saline in CRSwNP patients. The sinus mucosal specimens were harvested from the ethmoid cavity of 48 patients with CRSwNP and further subjected to hematoxylin–eosin staining and microbiology analysis. The biofilm-forming capacity of isolated bacterial strains was detected by microtiter-plate method and the effects of therapeutic doses of mometasone, fluticasone, isotonic and hypertonic saline on biofilm production were investigated. Bacterial strains were isolated in 42 (87.5%) patients: one organism in 34 (80.9%) and two organisms in 8 (19.1%). Staphylococcus epidermidis (34%) and Staphylococcus aureus (28%) were the most prevalent bacteria in biofilms of CRSwNP patients. Corticosteroids and saline solutions significantly reduced biofilm formation (p < 0.01 and p < 0.05, respectively) with better efficacy of fluticasone and isotonic nasal saline. Treatment with fluticasone, mometasone, isotonic and hypertonic nasal saline completely prevented biofilm production in 66, 50, 84 and 38% of bacterial strains, respectively. The most significant density reduction was observed in biofilm formed by Staphylococcus aureus, Pseudomonas aeruginosa and Streptococcus pneumoniae compared to other bacterial species (p < 0.01, p < 0.05, p < 0.05, respectively). The antibiofilm effects of corticosteroids and saline solutions also greatly depended on bacterial biomass (p < 0.05), with the most significant effect on high compared to small amount of formed biofilm. The topical steroids and nasal saline are shown to be potent antibiofilm agents in patients with CRSwNP. The effects of tested compounds depend on bacterial species and volume of formed biofilm.



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