Ιατρικά Άρθρα Αλέξανδρος Γ. Σφακιανάκης: 01/07/18

Κυριακή 7 Ιανουαρίου 2018

Acknowledgment to reviewers

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Are medical associations relevant to young doctors? [News]

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Repeated influenza vaccination for preventing severe and fatal influenza infection in older adults: a multicentre case-control study [Research]

BACKGROUND:

The effectiveness of repeated vaccination for influenza to prevent severe cases remains unclear. We evaluated the effectiveness of influenza vaccination on preventing admissions to hospital for influenza and reducing disease severity.

METHODS:

We conducted a case–control study in 20 hospitals in Spain during the 2013/14 and 2014/15 influenza seasons. Community-dwelling adults aged 65 years or older who were admitted to hospital for laboratory-confirmed influenza were matched with inpatient controls by sex, age, hospital and admission date. The effectiveness of vaccination in the current and 3 previous seasons in preventing influenza was estimated for inpatients with nonsevere influenza and for those with severe influenza who were admitted to intensive care units (ICUs) or who died.

RESULTS:

We enrolled 130 inpatients with severe and 598 with nonsevere influenza who were matched to 333 and 1493 controls, respectively. Compared with patients who were unvaccinated in the current and 3 previous seasons, adjusted effectiveness of influenza vaccination in the current and any previous season was 31% (95% confidence interval [CI] 13%–46%) in preventing admission to hospital for nonsevere influenza, 74% (95% CI 42%–88%) in preventing admissions to ICU and 70% (95% CI 34%–87%) in preventing death. Vaccination in the current season only had no significant effect on cases of severe influenza. Among inpatients with influenza, vaccination in the current and any previous season reduced the risk of severe outcomes (adjusted odds ratio 0.45, 95% CI 0.26–0.76).

INTERPRETATION:

Among older adults, repeated vaccination for influenza was twice as effective in preventing severe influenza compared with nonsevere influenza in patients who were admitted to hospital, which is attributable to the combination of the number of admissions to hospital for influenza that were prevented and reduced disease severity. These results reinforce recommendations for annual vaccination for influenza in older adults.

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Considering transparency and value for fairer drug prices [News]

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Perineural spread of skin cancer presenting as diplopia [Practice]

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A short history of pain management [News]

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Lancisi sign in a 69-year-old man with severe tricuspid regurgitation [Practice]

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Laying the digital and analytical foundations for Canadas future health care system [Commentary]

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From Queen Victoria to Sausage Pants: art in the superhospital [Humanities]

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New ammunition in the fight to label unhealthy foods [News]

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Doctors share responsibility for damaging discourse [Letters]

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Study by proponent of neck vein-widening therapy for MS finds treatment ineffective [News]

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Tax changes should be seen as a gateway to a larger discussion on reform of public health care in Canada [Letters]

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Some medical associations see modest growth despite challenges [News]

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Rabdocoestin B exhibits antitumor activity by inducing G2/M phase arrest and apoptosis in esophageal squamous cell carcinoma

Abstract

Purpose

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive squamous cell carcinomas and is generally resistant to chemotherapy. In the present study, the cytotoxic activity of Rabdocoestin B (Rabd-B) against ESCC and the underlying mechanisms were investigated.

Methods

The inhibitory effect of Rabd-B on KYSE30 and KYSE450 was evaluated by Cell Counting Kit-8 (CCK8) and colony formation assays in vitro. The cell cycle distribution and apoptosis of cells treated with Rabd-B were determined by flow cytometry. The mechanisms underlying the effects of Rabd-B were systematically examined by Western blot. The in vivo anti-tumor ability of Rabd-B was measured in mouse xenograft models and cisplatin (DDP) was used as positive control.

Results

Rabd-B efficiently induced G2/M phase arrest in ESCC cells by upregulating the Chk1/Chk2-Cdc25C axis to inhibit the G2→M transition facilitated by Cdc2/Cyclin B1. Furthermore, Rabd-B suppressed ATM/ATR phosphorylation, thereby inhibiting BRCA1-mediated DNA repair, which resulted in mitotic catastrophe and induced cell apoptosis. Rabd-B also decreased the activity of the Akt and NF-κB survival signaling pathways and ultimately initiated the caspase-9-dependent intrinsic apoptotic pathway in ESCC cells. The apoptosis induced by Rabd-B could be partially reversed by a caspase-9-specific inhibitor (Z-LEHD-FMK) and a pan-caspase inhibitor (Z-VAD-FMK). Moreover, Rabd-B effectively suppressed tumor growth in mouse xenografts which was comparable to that of DDP without significant injuries to the mice.

Conclusion

Taken together, these findings indicate that Rabd-B is a promising precursor compound that may be useful as a treatment for ESCC and thus warrants further investigation.

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Short course of cyclosporin A as a treatment option for drug-induced hypersensitivity syndrome: Case reports and review of the published work

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Health care disparities among octogenarians and nonagenarians with stage III lung cancer

BACKGROUND

To the authors' knowledge, the practice patterns for patients aged more than 80 years with stage III non-small cell lung cancer (NSCLC) is not well known. The purpose of the current study was to investigate factors predictive of and the impact on overall survival (OS) after concurrent chemoradiation (CRT) among patients aged ≥80 years with American Joint Committee on Cancer stage III NSCLC in the National Cancer Data Base (NCDB).

METHODS

In the NCDB, patients aged ≥80 years who were diagnosed with stage III NSCLC from 2004 to 2013 with complete treatment records were identified. Multivariable logistic regression and Cox proportional hazard models were generated and propensity score-matched analysis was used.

RESULTS

A total of 12,641 patients met the entry criteria: 6018 (47.6%) had stage IIIA disease and 6623 (52.4%) had stage IIIB disease. The median age at the time of diagnosis was 83.0 years (range, 80-91 years). A total of 7921 patients (62.7%) received no therapy. Black race (odds ratio [OR], 1.23; 95% confidence interval [95% CI], 1.06-1.43) and living in a lower educated census tract of residence (OR, 1.20; 95% CI, 1.03-1.40) were found to be associated with not receiving care, whereas treatment at an academic center (OR, 0.80; 95% CI, 0.70-0.92) was associated with receiving cancer-directed therapy. Receipt of no treatment (hazard ratio [HR], 2.69; 95% CI, 2.57-2.82) or definitive radiation alone (HR, 1.15; 95% CI, 1.07-1.24) compared with CRT was associated with worse OS. On propensity score matching, not receiving CRT was found to be associated with worse OS (HR, 1.58; 95% CI, 1.44-1.72).

CONCLUSIONS

In this NCDB analysis, approximately 62.7% of patients aged ≥80 years with stage III NSCLC received no cancer-directed care. Black race and living in a lower educated census tract were associated with not receiving cancer-directed care. OS was found to be improved in patients receiving CRT. Cancer 2018. © 2018 American Cancer Society.

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Respiratory syncytial virus

Respiratory syncytial virus: A virus that causes mild respiratory infections, colds, and coughs in adults and can produce severe respiratory problems, including bronchitis and pneumonia, in young children and anyone with compromised immune, cardiac, or pulmonary systems. Abbreviated RSV. RSV is spread via respiratory secretions and is highly contagious. Infections usually occur during annual community outbreaks, often lasting 4 to 6 months, during the late fall, winter, or early spring. RSV typically features fever, prominent nasal secretions, and congestion coupled with wheezing for 1 to 2 weeks. Having immunity against RSV requires having a continuous, solid level of antibodies against the virus. There is particular concern about RSV occurring in premature babies, because their immune systems lack maturity and antibodies. There is no RSV vaccine.

MedTerms (TM) is the Medical Dictionary of MedicineNet.com.
We Bring Doctors' Knowledge To You

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Correction to: Selective determination of mandelic acid in urine using molecularly imprinted polymer in microextraction by packed sorbent

Abstract

In the original publication of the article, there is an error in Fig. 2c. The authors would like to correct this error and the corrected version of Fig. 2c is as follow.

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Somatic mutations activating Wiskott-Aldrich syndrome protein concomitant with RAS pathway mutations in Juvenile myelomonocytic leukemia patients

Abstract

The WAS gene product is expressed exclusively in the cytoplasm of hematopoietic cells and constitutional genetic abrogation of WASP leads to Wiskott-Aldrich syndrome (WAS). Moreover, mutational activation of WASP has been associated with X-linked neutropenia (XLN). Although studies reported that patients with constitutional WAS mutations affecting functional WASP expression may present Juvenile MyeloMonocytic Lukemia (JMML)-like features, confounding differential diagnosis above all in the co-presence of mutated RAS, an activating somatic mutation of WASP has not been previously described in JMML patients.

In our ongoing studies on JMML genomics, we at first detected a somatic WAS mutation in a major clone found at two consecutive relapses in one of two twins with JMML. Both twins were treated with HSCT after diagnosis of JMML. The somatic WAS mutation detected here displayed an activating WASP phenotype. Screening of 46 sporadic JMML patients at disease onset for mutations in the same PBD domain of WAS revealed two additional singleton patients carrying minor mutated clones. This is the first study to associate somatically acquired WASP mutations with a hematopoietic malignancy and increases insight in the complexity of the genomic landscape of JMML that shows low recurrent mutations concomitant with general hyperactivation of RAS pathway signaling.

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Origin and effect factors of sedimentary organic carbon in a karst groundwater-fed reservoir, South China

Abstract

Reservoirs are commonly recharged by groundwater that is rich in bicarbonate ions in karst regions of South China, and the recharge of this groundwater to the reservoir can affect the biogeochemical processes of carbon sedimentation at the reservoir bottom. In this study, Dalongdong Reservoir, which is mainly recharged by two subterranean streams, was investigated based on a 42-cm-thick sedimentary core and the ²¹⁰Pb/¹³⁷Cs dating technique and isotope analyses to understand the sedimentary history and identify the carbon sources. The ²¹⁰Pb/¹³⁷Cs age model showed that the sediments were accumulated over the last 60 years. The annual increase precipitation and temperature showed no obvious change compared with trends of δ¹³C in total organic carbon (δ¹³C_org), δ¹⁵N values in total nitrogen, and the carbon and nitrogen ratio (C/N). This shows that climate was not the main control of the variation in sediment factors. Based on δ¹³C_org, δ¹⁵N, C/N, and isotopic mixing modeling, sources of organic carbon in the sediments were derived from plankton (60.84%), soil (22.93%), waste water (14.56%), and terrestrial plants (1.67%). From 1958 to 1978, reservoir establishment and leakage affected the contribution of the four sources. The contribution of the plankton source increased from 1978 to 2015, resulting from change of water level and continued input of external nitrogen. However, because of the revegetation supplied by an economic aid project the contribution of soil showed a considerable decreasing trend from 1978 to 2002. After 2002, For “Grain for Green” project, the contribution from soil further decreased. After reservoir construction, the contribution of waste water stabilized. The contribution of terrestrial plants started increased rapidly after 2002. Karst groundwater, which contains more dissolved inorganic carbon containing lower δ¹³C_DIC than the water sources of other lakes or reservoirs, makes the δ¹³C_org value of sediment more negative by phytoplankton photosynthesis in the reservoir.

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Rabdocoestin B exhibits antitumor activity by inducing G2/M phase arrest and apoptosis in esophageal squamous cell carcinoma

Abstract

Purpose

Methods

Results

Conclusion

Taken together, these findings indicate that Rabd-B is a promising precursor compound that may be useful as a treatment for ESCC and thus warrants further investigation.

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Roots of Unity Turns Five

Happy birthday, dear blog!

-- Read more on ScientificAmerican.com

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Pro/Antigenotoxic Activity of Usnic Acid Enantiomers In Vitro

The effect of usnic acid enantiomers on the genotoxic effects of dioxidine and methyl methanesulfonate was studied in vitro in human peripheral blood lymphocytes by the DNA comet method. We found that usnic acid enantiomers in a concentration range of 0.01-1.00 μM demonstrated pronounced antigenotoxic activity and reduced DNA damage induced by genotoxicants by 37-70%. In the same concentration range, the test enantiomers reduced the level of atypical DNA comets (hedgehogs) induced by genotoxicants by 23-61%. The test compounds did not modulate the effects of genotoxicants in a concentration of 10 μM and potentiated them in a concentration of 100 μM. The modifying activity of usnic acid did not depend on spatial configuration and on the used model genotoxicant.

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Particular Role of JAK/STAT3 Signaling in Functional Control of Mesenchymal Progenitor Cells

The role of JAK/STAT3-mediated signaling pathway in the realization of the growth potential of mesenchymal precursor cells was examined in vitro. The stimulating role of JAKs and STAT3 towards proliferating activity of progenitor cells and their different role in the regulation of differentiation of the progenitor elements were demonstrated. Inhibitors of JAKs and STAT3 reduced the yield of fibroblast CFU and their mitotic activity. Blockade of JAKs accelerated and selective inactivation of STAT3 decelerated differentiation of progenitor cells.

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Collagen Implant and Mononuclear Cells of Umbilical Blood Allow the Restore of Movements of Hind Limbs after Removing the Site of Spinal Cord

Replacement of the removal site of the spinal cord on a collagen implant restores the motor function of the hind limbs in rats to the level of movements in the two joints for 8 weeks. After intravenous administration of mononuclear cells of human umbilical blood, recovery accelerated, significantly improved to the level of motion in the three joints, and there is a tendency to improve further recovery of movements.

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Dynamics of Distribution of Capillaries with Matrix Metalloproteinase-2 and Its Tissue Inhibitor in Rat Brain during Development of Experimental Hypertension

The capillaries containing MMP-2 and its tissue inhibitor TIMP-2 were examined in cerebral cortex and white matter obtained from intact Wistar rats (n=5) and the rats with progressing experimental renovascular hypertension (n=35). In hypertensive rats, the changes in intensity of the immunohistochemical reaction and in the density of capillaries expressing TIMP-2 significantly differed from the corresponding values in MMP-2-positive capillaries, which resulted in pronounced deviation of MMP-2/TIMP-2 index from the control level (especially in cerebral cortex) probably attesting to enhanced risk of complications in cases with arterial hypertension.

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Inducible NO Synthase mRNA Expression and Infiltration of Rats Myocardium with Inflammatory Cells in 2-4 Hours after Modeled Permanent Ischemia or Ischemia/Reperfusion

Expression of inducible NO-synthase mRNA and myocardial infiltration with neutrophils were studied in rats with modeled permanent ischemia and ischemia/reperfusion models. Expression of inducible NO synthase mRNA in the ischemic region increased significantly in 3, 3.5, and 4 h in modeled ischemia/reperfusion and in 3.5 and 4 h in permanent ischemia. Myocardial infiltration with neutrophils was significantly higher than in intact controls throughout the experiment without significant intergroup differences. In non-ischemic myocardium, enhanced expression of inducible NO synthase mRNA and moderate neutrophilic-lymphocytic myocardial infiltration were also observed in 3.5, and 4 h after ischemia.

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Potentiation of Otoprotective Effect of Hydrocortisone Immobilized on Povidone Nanoparticles under Conditions of Intravenous Injection

The otoprotective effect of immobilized hydrocortisone was studied on the model of acute acoustic injury to the auditory analyzer in male Wistar rats. The effects of true solution and suspension where polyvinylpyrrolidone particles (100-500 nm) served as dispersed phase (hydrocortisone concentration 5 mg/kg). The agents were administered immediately after continuous acoustic stimulation: 5 kHz tone, 110 dB for 2 h. The hearing status was evaluated by the amplitude of otoacoustic emission at the distortion product frequency (4-6.4 kHz) 1 and 24 h and 7 days after acoustic stimulation. Single injection of hydrocortisone suspension caused a more pronounced therapeutic effect within 1 day after acoustic stimulation.

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Connection between Parameters of Erythron System and Myelofibrosis during Chronic Myeloleukemia, Multiply Mieloma, and Chronic Lymphatic Leukemia

Clinical and morphological investigation of myelofibrosis was performed in patients with chronic myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia by analyzing the morphometric parameters of trepan-biopsy material. The correlation between changes in the parameters of erythron system and distribution of myelofibrosis were analyzed. In patients with chronic myeloid leukemia, multiple myeloma, and chronic lymphocytic leukemia, the maximum suppression of the erythron was observed against the background of severe myelofibrosis. The degree of erythron inhibition correlated with distribution of the fibrous tissue in the bone marrow. In patients with onset of chronic phase of chronic myeloid leukemia and active phase of multiple myeloma, the total number of erythroid cells was lower than in active phase of chronic lymphocytic leukemia irrespective of the degree of myelofibrosis. Erythrocyte count and hemoglobin content in the peripheral blood were lower in patients with multiple myeloma and chronic lymphocytic leukemia in comparison with the corresponding parameters in patients with chronic myeloid leukemia irrespective of the severity of myelofibrosis.

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Signal Mechanism of the Protective Effect of Combined Preconditioning by Amtizole and Moderate Hypoxia

The content of regulatory proteins involved in adaptation to hypoxia and ischemia was studied in brain rat homogenate under conditions of normoxia and after bilateral ligation of the common carotid arteries. Preconditioning with amtizole in combination with moderate hypoxia increased the levels of HIF-1α, erythropoietin, vascular endothelial growth factor under conditions of normoxia. During experimental ischemia, combined preconditioning led to stabilization of the content of these regulatory proteins at the level of intact control and to a decrease in glycogen synthase-3β kinase activity. This pattern of changes in regulatory proteins was noted during the early and late periods of preconditioning.

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Algorithm of Molecular and Biological Assessment of the Mechanisms of Sensitivity to Drug Toxicity by the Example of Cyclophosphamide

Comparative study of the liver, blood, and spleen of DBA/2JSto and BALB/cJLacSto mice sensitive and resistant to acute toxicity of the cyclophosphamide allowed us to reveal basic toxicity biomarkers of this antitumor and immunosuppressive agent. Obtained results can be used for the development of an algorithm for evaluation of toxic effects of drugs and food components.

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A Marker of Cerebral Ischemia in Solid State Structures of Blood Serum

Reversible cerebral ischemia of medium severity was reproduced in male Wistar rats by bilateral occlusion of the common carotid arteries. Solid-phase structures (anisomorphons) were obtained by marginal dehydration of the serum. Small focal isotropic defects in the serum anisomorphon texture were found in 100% cases during occlusion of the carotid arteries. Similar signs were detected in all patients with chronic cerebral ischemia, which proved specificity of this morphological marker of the disease.

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Experimental Modeling of Alcohol-Induced Liver Cirrhosis in Rats

An experimental model of alcohol-induced liver cirrhosis in white outbred rats was developed: intragastric administration of 40% ethanol (3 g/kg) every other day for 3 weeks and simultaneous intraperitoneal administration of 1% of N-nitrozodimethylamine (5 mg/kg) for 4 consecutive days of each week.

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The Role of Succinate in Regulation of Immediate HIF-1α Expression in Hypoxia

Hypoxia-induced immediate expression of transcription factor HIF-1α in the brain cortex is regulated by succinate produced in both the tricarbonic acid cycle and GABA shunt reactions and is induced by succinate-containing drugs. These facts prove the existence of succinate-dependent signalling regulation involved in immediate and delayed molecular adaptation and increased body resistance to oxygen deficiency, where succinate acts as a signal molecule. The intensity of this process differs in animals with low and high resistance to hypoxia.

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Inactivation of M111 Protein Gene Modifies Streptococcus Pyogenes Interactions with Mouse Macrophages In Vitro

Immunomodulatory properties of S. pyogenes protein M111 were studied on the model of Gurov strain and its isogenic mutant not expressing M protein. Mouse resident peritoneal macrophages were incubated with bacteria and generation of nitroxide and superoxide anions and production of IL-6, IL-10, and IL-17 were evaluated. Protein M111 modified macrophage response: it exhibited antiphagocytic activity, prevented ROS formation, and stimulated the production of anti-inflammatory cytokine IL-10. The results suggested that this protein could serve in the bacteria as a factor suppressing the host defense forces and promoting the realization of the strategy beneficial for pathogens — escape from the host immune defense.

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Immunohistochemical Features of O6-Methylguanine-DNA Methyltransferase Expression during Ovarian Endometriosis

A comparative immunohistochemical study for the expression of O6-methylguanine-DNA methyltransferase (MGMT) was performed in tissues of the eutopic endometrium and ovarian endometriosis. The highest level of MGMT expression in eutopic endometrial tissue was observed in epitheliocyte nuclei during the proliferative phase. In regions of endometriosis the expression of MGMT in epitheliocyte nuclei was shown to increase during stages I and II, but decreased in stages III and IV. The progression of endometriosis was accompanied by a gradual increase of study parameters in the nuclei and cytoplasm of stromal cells. These changes reflect the impairment of DNA reparation, which probably serves as a stage in the development and progression of endometriosis.

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Cellular Mechanisms of Aortic Valve Calcification

Comparative in vitro study examined the osteogenic potential of interstitial cells of aortic valve obtained from the patients with aortic stenosis and from control recipients of orthotopic heart transplantation with intact aortic valve. The osteogenic inductors augmented mineralization of aortic valve interstitial cells (AVIC) in patients with aortic stenosis in comparison with the control level. Native AVIC culture of aortic stenosis patients demonstrated overexpression of osteopontin gene (OPN) and underexpression of osteoprotegerin gene (OPG) in comparison with control levels. In both groups, AVIC differentiation was associated with overexpression of RUNX2 and SPRY1 genes. In AVIC of aortic stenosis patients, expression of BMP2 gene was significantly greater than the control level. The study revealed an enhanced sensitivity of AVIC to osteogenic inductors in aortic stenosis patients, which indicates probable implication of OPN, OPG, and BMP2 genes in pathogenesis of aortic valve calcification.

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A Technique for In Vitro Studying of the Permeability of the Spinal Cord Dura Mater

We propose an in vitro method for studying permeability of spinal cord dura mater for components of autological serum using an original device. Sixty native samples of the spinal cord dura mater obtained from 12 mongrel dogs were used for testing of the device. The coefficient of permeability variation (V) for blood serum substances did not exceed 5% in most cases excluding lactate (V=8.03%). Analysis of spinal cord dura mater permeability in vitro for various substances using the developed device provides reproducible results with acceptable variability (5-10%).

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Comparison of Morphology of Adipose Body of the Orbit and Subcutaneous Fat in Humans

We compared histological structure of the orbital and subcutaneous adipose tissue. Quantitative morphometry showed that the mean diameter of adipocytes and their volume density in the orbital adipose tissue were significantly lower than in the subcutaneous fat, while volume density of vessels and elements of the connective tissue in the orbital adipose tissue was higher. Previously known and revealed here differences in the structure of orbital and subcutaneous adipose tissue do not answer the question, whether subcutaneous adipose tissue can be used for replacement of the orbital tissue deficit.

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Thyroid Top-Read Articles of 2017

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FREE ACCESS through January 16, 2018.
Read now:

Latest Impact Factor: 5.515
The Official Journal of: American Thyroid Association

The 2017 Bethesda System for Reporting Thyroid Cytopathology
Edmund S. Cibas, Syed Z. Ali

Subclinical Hypothyroidism in Pregnancy: A Systematic Review and Meta-Analysis
Spyridoula Maraka, Naykky M. Singh Ospina, Derek T. O’Keeffe, Ana E. Espinosa De Ycaza, Michael R. Gionfriddo, Patricia J. Erwin, Charles C. Coddington III, Marius N. Stan, M. Hassan Murad, Victor M. Montori

Impact of the Multi-Gene ThyroSeq Next-Generation Sequencing Assay on Cancer Diagnosis in Thyroid Nodules with Atypia of Undetermined Significance/Follicular Lesion of Undetermined Significance Cytology
Yuri E. Nikiforov, Sally E. Carty, Simon I. Chiosea, Christopher Coyne, Umamaheswar Duvvuri, Robert L. Ferris, William E. Gooding, Shane O. LeBeau, N. Paul Ohori, Raja R. Seethala, Mitchell E. Tublin, Linwah Yip, Marina N. Nikiforova

Incidences of Unfavorable Events in the Management of Low-Risk Papillary Microcarcinoma of the Thyroid by Active Surveillance Versus Immediate Surgery
Hitomi Oda, Akira Miyauchi, Yasuhiro Ito, Kana Yoshioka, Ayako Nakayama, Hisanori Sasai, Hiroo Masuoka, Tomonori Yabuta, Mitsuhiro Fukushima, Takuya Higashiyama, Minoru Kihara, Kaoru Kobayashi, Akihiro Miya

Thyroid Ultrasound Features and Risk of Carcinoma: A Systematic Review and Meta-Analysis of Observational Studies
Luciana Reck Remonti, Caroline Kaercher Kramer, Cristiane Bauermann Leitão, Lana Catani F. Pinto, Jorge Luiz Gross

The post <i>Thyroid</i> Top-Read Articles of 2017 appeared first on American Thyroid Association.

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Ecotoxicology and toxicology: problems and decisions

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Incorporating Contagion in Portfolio Credit Risk Models Using Network Theory

Portfolio credit risk models estimate the range of potential losses due to defaults or deteriorations in credit quality. Most of these models perceive default correlation as fully captured by the dependence on a set of common underlying risk factors. In light of empirical evidence, the ability of such a conditional independence framework to accommodate for the occasional default clustering has been questioned repeatedly. Thus, financial institutions have relied on stressed correlations or alternative copulas with more extreme tail dependence. In this paper, we propose a different remedy—augmenting systematic risk factors with a contagious default mechanism which affects the entire universe of credits. We construct credit stress propagation networks and calibrate contagion parameters for infectious defaults. The resulting framework is implemented on synthetic test portfolios wherein the contagion effect is shown to have a significant impact on the tails of the loss distributions.

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Seroprevalence and Associated Risk Factors of Brucellosis among Indigenous Cattle in the Adamawa and North Regions of Cameroon

A cross-sectional seroprevalence study was conducted on cattle in the North and Adamawa Regions of Cameroon to investigate the status of bovine brucellosis and identify potential risk factors. The diagnosis was carried out using the Rose Bengal Plate test (RBPT) and indirect ELISA (i-ELISA), while questionnaires were used to evaluate risk factors for bovine brucellosis in cattle. The Bayesian approach was used to evaluate the diagnostic tests’ sensitivity and specificity. The overall individual level () and herd level () seroprevalence were 5.4% (0.4–10.5) and 25.6% (16.2–35.0), respectively. Bayesian analysis revealed sensitivity of 58.3% (26.4–92.7) and 89.6% (80.4–99.4) and specificity of 92.1% (88.7–95.2) and 95.7% (91.1–99.7) for RBPT and i-ELISA, respectively. Management related factors such as region, locality, herd size, and knowledge of brucellosis and animal related factors such as sex and age were significantly associated with seropositivity of brucellosis. Zoonotic brucellosis is a neglected disease in Cameroon. The study highlights the need for control measures and the need to raise public awareness of the zoonotic occurrence and transmission of bovine brucellosis in the country. An integrated disease control strategy mimicking the one health approach involving medical personnel, veterinarians, related stakeholders, and affected communities cannot be overemphasized.

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The Rare Togetherness of Bladder Leiomyoma and Neurofibromatosis

Neurofibromatosis Type 1 (Von Recklinghausen disease) is a common, autosomal dominant hereditary disorder characterized by involvement of multiple tissues derived from the neural crest. Urinary system involvement in neurofibromatosis is a rare condition. Leiomyoma of the bladder is a rare benign mesenchymal tumor. In this case, our experience and approach regarding the bladder leiomyoma development in a patient diagnosed with neurofibromatosis are presented and the literature data has been reviewed.

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An Imputation Method for Missing Traffic Data Based on FCM Optimized by PSO-SVR

Missing traffic data are inevitable due to detector failure or communication failure. Currently, most of imputation methods estimated the missing traffic values by using spatial-temporal information as much as possible. However, it ignores an important fact that spatial-temporal information of the traffic missing data is often incomplete and unavailable. Moreover, most of the existing methods are verified by traffic data from freeway, and their applicability to urban road data needs to be further verified. In this paper, a hybrid method for missing traffic data imputation is proposed using FCM optimized by a combination of PSO algorithm and SVR. In this method, FCM is the basic algorithm and the parameters of FCM are optimized. Firstly, the patterns of missing traffic data are analyzed and the representation of missing traffic data is given using matrix-based data structure. Then, traffic data from urban expressway and urban arterial road are used to analyze spatial-temporal correlation of the traffic data for the determination of the proposed method input. Finally, numerical experiment is designed from three perspectives to test the performance of the proposed method. The experimental results demonstrate that the novel method not only has high imputation precision, but also exhibits good robustness.

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An Analysis of the Physical Characteristics of the Summer Low Atmosphere in the Gobi Desert Adjacent to Bosten Lake, Xinjiang, China

A month-long field observation campaign was conducted, which covered approximately 100 km2 of the Gobi Desert area on the southeast bank of Bosten Lake during the summer of 2016. The purpose of the study was to examine the physical characteristics of the low atmosphere over land-lake nonuniform underlying surfaces in the Gobi Desert of northwestern China. The results of the statistical analysis showed that, during the observational period, the average daytime surface horizontal thermal gradient reached up to −0.2°C/km from the lakeshore to southern Gobi Desert area. The near-surface wind field of the 7 km horizontal extent from the lakeshore was dominated by onshore breezes with average peak wind speeds above 5 m/s. In the atmospheric near-surface layer, an isohumidity layer at a height between 10 and 50 m a.g.l. was observed from 11:00 to 18:00 LST. Also, a case study for the atmospheric boundary layer and local circulation analyses was conducted. The onshore breezes were found to play a major role in the vertical structure of the local atmospheric boundary layer. The numerical simulation results indicated that there was an alternating day-night local circulation in the Bosten Lake area.

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Zanthoxylum ailanthoides Suppresses Oleic Acid-Induced Lipid Accumulation through an Activation of LKB1/AMPK Pathway in HepG2 Cells

Zanthoxylum ailanthoides (ZA) has been used as folk medicines in East Asian and recently reported to have several bioactivity; however, the studies of ZA on the regulation of triacylglycerol (TG) biosynthesis have not been elucidated yet. In this study, we examined whether the methanol extract of ZA (ZA-M) could reduce oleic acid- (OA-) induced intracellular lipid accumulation and confirmed its mode of action in HepG2 cells. ZA-M was shown to promote the phosphorylation of AMPK and its upstream LKB1, followed by reduction of lipogenic gene expressions. As a result, treatment of ZA-M blocked de novo TG biosynthesis and subsequently mitigated intracellular neutral lipid accumulation in HepG2 cells. ZA-M also inhibited OA-induced production of reactive oxygen species (ROS) and TNF-α, suggesting that ZA-M possess the anti-inflammatory feature in fatty acid over accumulated condition. Taken together, these results suggest that ZA-M attenuates OA-induced lipid accumulation and inflammation through the activation of LKB1/AMPK signaling pathway in HepG2 cells.

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Automated Whole-Body Bone Lesion Detection for Multiple Myeloma on 68Ga-Pentixafor PET/CT Imaging Using Deep Learning Methods

The identification of bone lesions is crucial in the diagnostic assessment of multiple myeloma (MM). 68Ga-Pentixafor PET/CT can capture the abnormal molecular expression of CXCR-4 in addition to anatomical changes. However, whole-body detection of dozens of lesions on hybrid imaging is tedious and error prone. It is even more difficult to identify lesions with a large heterogeneity. This study employed deep learning methods to automatically combine characteristics of PET and CT for whole-body MM bone lesion detection in a 3D manner. Two convolutional neural networks (CNNs), V-Net and W-Net, were adopted to segment and detect the lesions. The feasibility of deep learning for lesion detection on 68Ga-Pentixafor PET/CT was first verified on digital phantoms generated using realistic PET simulation methods. Then the proposed methods were evaluated on real 68Ga-Pentixafor PET/CT scans of MM patients. The preliminary results showed that deep learning method can leverage multimodal information for spatial feature representation, and W-Net obtained the best result for segmentation and lesion detection. It also outperformed traditional machine learning methods such as random forest classifier (RF), -Nearest Neighbors (k-NN), and support vector machine (SVM). The proof-of-concept study encourages further development of deep learning approach for MM lesion detection in population study.

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Corrigendum to “All-Atom Four-Body Knowledge-Based Statistical Potentials to Distinguish Native Protein Structures from Nonnative Folds”

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Raptor Raptor Raptor, Part 1

raptors-2018-Raptors-kill-big-animals-No

A quick look at the history and diversity of the birds of prey...

-- Read more on ScientificAmerican.com

feed?i=WdJ6AAxx6pI:zWONDM2AATw:gIN9vFwOq

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Improved depiction of atherosclerotic carotid artery stenosis in virtual monoenergetic reconstructions of venous phase Dual-Layer Computed Tomography in comparison to polyenergetic reconstructions

Publication date: Available online 6 January 2018
Source:European Journal of Radiology
Author(s): David Zopfs, Simon Lennartz, Kai Laukamp, Nils Große Hokamp, Anastasios Mpotsaris, David Maintz, Jan Borggrefe, Victor Neuhaus
ObjectivesTo compare virtual monoenergetic images (VMI) reconstructed from venous phase Dual-Layer CT (DLCT) with polyenergetic images (PI) of DLCT-Angiography (DLCT-A) regarding vessel contrast and image quality especially in sight to atherosclerotic carotid artery stenosis.Methods & materials25 DLCT-A and 55 venous phase DLCT were analyzed in this retrospective study. For objective analysis PI and VMI (40–120 keV) were assessed comparing attenuation, standard deviation, signal-/contrast- to noise ratios (SNR, CNR) in the common carotid artery (CCA), vertebral artery, sternocleidomastoid muscle and air. For subjective analysis, vessel contrast, delineation of the superficial temporal artery, depiction of calcified plaque as well as vessel patency within the atherosclerotic stenosis of the internal carotid artery were rated and the extent of the calcified plaque and remaining vessel lumen were measured in venous phase DLCT.ResultsIn venous phase DLCT, attenuation, SNR and CNR in the CCA increased with lower keV. Attenuation, SNR and CNR at 40 keV in the CCA were comparable to PI of DLCT-A (all: p > 0.05). Subjective image contrast, assessment of vessel patency within a stenosis as well as delineation of the superficial temporal artery were rated superior at 40–60 keV in comparison to PI of venous phase DLCT (all: p ≤ 0.05). Slightly more blooming of the atherosclerotic plaque was found in VMI at 40–60 keV. There was no difference of NASCET-criteria of carotid stenosis between VMI at different keV-levels and PI (p = 1.0).ConclusionVMI at 40 keV reconstructed from venous phase DLCT yield an image quality equal to CT-Angiography, especially regarding vessel contrast. Perception and assessment of the carotid artery within an atherosclerotic stenosis are not impaired at low keV.

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Issue Information

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SGK2

Although this gene product is similar to serum- and glucocorticoid-induced protein kinase (SGK), this gene is not induced by serum or glucocorticoids. This gene is induced ... "Regulation of KCNE1-dependent K(+) current by the serum and glucocorticoid-inducible kinase (SGK) isoforms". Pflugers Arch.

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Learn the SIOG guidelines for the management of chronic lymphocytic leukaemia in elderly patients:… https://t.co/Qfs4nWX6vF

Learn the SIOG guidelines for the management of chronic lymphocytic leukaemia in elderly patients:… https://t.co/Qfs4nWX6vF

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Editorial Board

Publication date: January 2018
Source:Biological Psychology, Volume 131

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Cosmetics, Vol. 5, Pages 8: Potential Use of Spin Traps to Control ROS in Antipollution Cosmetics—A Review

Cosmetics, Vol. 5, Pages 8: Potential Use of Spin Traps to Control ROS in Antipollution Cosmetics—A Review

Cosmetics doi: 10.3390/cosmetics5010008

Authors: Prashant Sawant

Pollution from air and sunlight has adverse effects on human health, particularly skin health. It creates oxidative stress, which results in skin diseases, including skin cancer and aging. Different types of antioxidants are used as preventative actives in skin-care products. However, they have some limitations as they also scavenge oxygen. Recently, spin traps are being explored to trap free radicals before these radicals generating more free radicals (cascading effect) and not the oxygen molecules. However, not all spin traps can be used in the topical cosmetic skin-care products due to their toxicity and regulatory issues. The present review focuses on the different pathways of reactive oxygen species (ROS) generation due to pollution and the potential use of spin traps in anti-pollution cosmetics to control ROS.

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Laccase catalyzed elimination of morphine from aqueous systems

Publication date: Available online 6 January 2018
Source:New Biotechnology
Author(s): Daniela Huber, Klaus Bleymaier, Alessandro Pellis, Robert Vielnascher, Andreas Daxbacher, Katrin J. Greimel, Georg M. Guebitz
Pharmaceuticals contaminate the environment for several reasons, including metabolic excretion after intake, industrial waste and improper disposal. The narcotic drug morphine is commonly utilized for chronic pain management, and the distribution of morphine in aqueous systems and in waste waters is of high concern. Here. the removal of morphine by a laccase from Myceliophthora thermophila both in its free form as well as immobilized on Accurel MP1000 beads was investigated. Complete morphine elimination was achieved within 30 min for the free and the immobilized enzyme (70% bound protein) for concentrations between 1 and 1,000 mg L⁻¹ according to LC-TOF mass spectrometry analysis. Higher morphine concentrations up to 60 g L⁻¹ were also tested and total elimination was achieved within 6 h. Therefore, laccases are ideal candidates for removing morphine from aqueous systems.

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IJERPH, Vol. 15, Pages 87: Comparing U.S. Injury Death Estimates from GBD 2015 and CDC WONDER

IJERPH, Vol. 15, Pages 87: Comparing U.S. Injury Death Estimates from GBD 2015 and CDC WONDER

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15010087

Authors: Yue Wu Xunjie Cheng Peishan Ning Peixia Cheng David Schwebel Guoqing Hu

Objective: The purpose of the present study was to examine consistency in injury death statistics from the United States CDC Wide-ranging Online Data for Epidemiologic Research (CDC WONDER) with those from GBD 2015 estimates. Methods: Differences in deaths and the percent difference in deaths between GBD 2015 and CDC WONDER were assessed, as were changes in deaths between 2000 and 2015 for the two datasets. Results: From 2000 to 2015, GBD 2015 estimates for the U.S. injury deaths were somewhat higher than CDC WONDER estimates in most categories, with the exception of deaths from falls and from forces of nature, war, and legal intervention in 2015. Encouragingly, the difference in total injury deaths between the two data sources narrowed from 44,897 (percent difference in deaths = 41%) in 2000 to 34,877 (percent difference in deaths = 25%) in 2015. Differences in deaths and percent difference in deaths between the two data sources varied greatly across injury cause and over the assessment years. The two data sources present consistent changes in direction from 2000 to 2015 for all injury causes except for forces of nature, war, and legal intervention, and adverse effects of medical treatment. Conclusions: We conclude that further studies are warranted to interpret the inconsistencies in data and develop estimation approaches that increase the consistency of the two datasets.

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IJERPH, Vol. 15, Pages 88: The Impact of Load Carriage on Measures of Power and Agility in Tactical Occupations: A Critical Review

IJERPH, Vol. 15, Pages 88: The Impact of Load Carriage on Measures of Power and Agility in Tactical Occupations: A Critical Review

International Journal of Environmental Research and Public Health doi: 10.3390/ijerph15010088

Authors: Aaron Joseph Amy Wiley Robin Orr Benjamin Schram J. Dawes

The current literature suggests that load carriage can impact on a tactical officer’s mobility, and that survival in the field may rely on the officer’s mobility. The ability for humans to generate power and agility is critical for performance of the high-intensity movements required in the field of duty. The aims of this review were to critically examine the literature investigating the impacts of load carriage on measures of power and agility and to synthesize the findings. The authors completed a search of the literature using key search terms in four databases. After relevant studies were located using strict inclusion and exclusion criteria, the studies were critically appraised using the Downs and Black Checklist and relevant data were extracted and tabled. Fourteen studies were deemed relevant for this review, ranging in percentage quality scores from 42.85% to 71.43%. Outcome measures used in these studies to indicate levels of power and agility included short-distance sprints, vertical jumps, and agility runs, among others. Performance of both power and agility was shown to decrease when tactical load was added to the participants. This suggests that the increase in weight carried by tactical officers may put this population at risk of injury or fatality in the line of duty.

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quality of care; +39 new citations

39 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results:

quality of care

These pubmed results were generated on 2018/01/07

PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

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IJMS, Vol. 19, Pages 175: Transcriptome Analysis in Haematococcus pluvialis: Astaxanthin Induction by High Light with Acetate and Fe2+

IJMS, Vol. 19, Pages 175: Transcriptome Analysis in Haematococcus pluvialis: Astaxanthin Induction by High Light with Acetate and Fe2+

International Journal of Molecular Sciences doi: 10.3390/ijms19010175

Authors: Bangxiang He Lulu Hou Manman Dong Jiawei Shi Xiaoyun Huang Yating Ding Xiaomei Cong Feng Zhang Xuecheng Zhang Xiaonan Zang

Haematococcus pluvialis is a commercial microalga, that produces abundant levels of astaxanthin under stress conditions. Acetate and Fe2+ are reported to be important for astaxanthin accumulation in H. pluvialis. In order to study the synergistic effects of high light stress and these two factors, we obtained transcriptomes for four groups: high light irradiation (HL), addition of 25 mM acetate under high light (HA), addition of 20 μM Fe2+ under high light (HF) and normal green growing cells (HG). Among the total clean reads of the four groups, 156,992 unigenes were found, of which 48.88% were annotated in at least one database (Nr, Nt, Pfam, KOG/COG, SwissProt, KEGG, GO). The statistics for DEGs (differentially expressed genes) showed that there were more than 10 thousand DEGs caused by high light and 1800–1900 DEGs caused by acetate or Fe2+. The results of DEG analysis by GO and KEGG enrichments showed that, under the high light condition, the expression of genes related to many pathways had changed, such as the pathway for carotenoid biosynthesis, fatty acid elongation, photosynthesis-antenna proteins, carbon fixation in photosynthetic organisms and so on. Addition of acetate under high light significantly promoted the expression of key genes related to the pathways for carotenoid biosynthesis and fatty acid elongation. Furthermore, acetate could obviously inhibit the expression of genes related to the pathway for photosynthesis-antenna proteins. For addition of Fe2+, the genes related to photosynthesis-antenna proteins were promoted significantly and there was no obvious change in the gene expressions related to carotenoid and fatty acid synthesis.

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Mitochondrial Network Responses in Oxidative Physiology and Disease

Publication date: Available online 6 January 2018
Source:Free Radical Biology and Medicine
Author(s): Young-Mi Go, Jolyn Fernandes, Xin Hu, Karan Uppal, Dean P. Jones
Mitochondrial activities are linked directly or indirectly to all cellular functions in aerobic eukaryotes. Omics methods enable new approaches to study functional organization of mitochondria and their adaptive and maladaptive network responses to bioenergetic fuels, physiologic demands, environmental challenges and aging. In this review, we consider mitochondria collectively within a multicellular organism as a macroscale “mitochondriome”, functioning to organize bioenergetics and metabolism as an organism utilizes environmental resources and protects against environmental threats. We address complexities of knowledgebase-driven functional mapping of mitochondrial systems and then consider data-driven network mapping using omics methods. Transcriptome-metabolome-wide association study (TMWAS) shows connectivity and organization of nuclear transcription with mitochondrial transport systems in cellular responses to mitochondria-mediated toxicity. Integration of redox and respiratory measures with TMWAS shows central redox hubs separating systems linked to oxygen consumption rate and H2O2 production. Combined redox proteomics, metabolomics and transcriptomics further shows that physiologic network structures can be visualized separately from toxicologic networks. These data-driven integrated omics methods create new opportunities for mitochondrial systems biology.

Graphical abstract

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Antibodies, Vol. 7, Pages 6: In-Depth Comparison of Lysine-Based Antibody-Drug Conjugates Prepared on Solid Support Versus in Solution

Antibodies, Vol. 7, Pages 6: In-Depth Comparison of Lysine-Based Antibody-Drug Conjugates Prepared on Solid Support Versus in Solution

Antibodies doi: 10.3390/antib7010006

Authors: Keith Arlotta Aditya Gandhi Hsiao-Nung Chen Christine Nervig John Carpenter Shawn Owen

Antibody drug conjugates are a rapidly growing form of targeted chemotherapeutics. As companies and researchers move to develop new antibody–drug conjugate (ADC) candidates, high-throughput methods will become increasingly common. Here we use advanced characterization techniques to assess two trastuzumab-DM1 (T-DM1) ADCs; one produced using Protein A immobilization and the other produced in solution. Following determination of payload site and distribution with liquid chromatography-mass spectrometry (LC/MS), thermal stability, heat-induced aggregation, tertiary structure, and binding affinity were characterized using differential scanning calorimetry (DSC), dynamic light scattering (DLS), Raman spectroscopy, and isothermal titration calorimetry (ITC), respectively. Small differences in the thermal stability of the CH2 domain of the antibody as well as aggregation onset temperatures were observed from DSC and DLS, respectively. However, no significant differences in secondary and tertiary structure were observed with Raman spectroscopy, or binding affinity as measured by ITC. Lysine-based ADC conjugation produces an innately heterogeneous population that can generate significant variability in the results of sensitive characterization techniques. Characterization of these ADCs indicated nominal differences in thermal stability but not in tertiary structure or binding affinity. Our results lead us to conclude that lysine-based ADCs synthesized following Protein A immobilization, common in small-scale conjugations, are highly similar to equivalent ADCs produced in larger scale, solution-based methods.

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Antioxidant and antibacterial evaluation of polysaccharides sequentially extracted from onion (Allium cepa L.)

Publication date: May 2018
Source:International Journal of Biological Macromolecules, Volume 111
Author(s): Yi-Long Ma, Dan-Ye Zhu, Kiran Thakur, Cai-Hong Wang, Hao Wang, Ya-Fei Ren, Jian-Guo Zhang, Zhao-Jun Wei
We investigated the antioxidant and antimicrobial potential of sequentially extracted onion polysaccharide fractions namely HBSS, CHSS, DASS and CASS. The different antioxidant assays indicated that ACLPs exhibited potentially appreciable antioxidant activity in a dose-dependent manner. Among all the fractions, CHSS rendered the highest antioxidant action towards ABTS radical cations (97.52%), Fe²⁺ chelating (98.94%) and superoxide anion radical scavenging (76.27%). Whereas, HBSS possessed the highest potential for DPPH radicals (93.68%), hydroxyl radicals (65.12%) as well as for reducing power (0.559). CASS exhibited the highest lipid peroxidation inhibition (86.43%), while, DASS showed the best β-carotene bleaching inhibition (92.26%). Furthermore, regardless of the bacterial strain, DASS represented the strongest antibacterial activity on the basis of largest inhibition zone, the lowest minimal inhibitory concentration and maximum inhibition of bacterial growth in liquid medium. Overall results indicated that ACLPs hold a promise as potential natural antioxidant additives and antimicrobial agents for formulating the functional foods with potential applications in the medical and food industries.

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Gambling in an Indian community-An emerging mental health issue for exploration.

Gambling in an Indian community-An emerging mental health issue for exploration.

Asian J Psychiatr. 2017 Dec 27;31:8-9

Authors: Sharma MK, Rao GN, Benegal V, Thennarasu K, Thomas D

PMID: 29306220 [PubMed - as supplied by publisher]

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Long-term observations of the background aerosol at Cabauw, The Netherlands.

Long-term observations of the background aerosol at Cabauw, The Netherlands.

Sci Total Environ. 2018 Jan 03;625:752-761

Authors: Mamali D, Mikkilä J, Henzing B, Spoor R, Ehn M, Petäjä T, Russchenberg H, Biskos G

Abstract
Long-term measurements of PM2.5 mass concentrations and aerosol particle size distributions from 2008 to 2015, as well as hygroscopicity measurements conducted over one year (2008-2009) at Cabauw, The Netherlands, are compiled here in order to provide a comprehensive dataset for understanding the trends and annual variabilities of the atmospheric aerosol in the region. PM2.5 concentrations have a mean value of 14.4μgm-3 with standard deviation 2.1μgm-3, and exhibit an overall decreasing trend of -0.74μgm-3year-1. The highest values are observed in winter and spring and are associated with a shallower boundary layer and lower precipitation, respectively, compared to the rest of the seasons. Number concentrations of particles smaller than 500nm have a mean of 9.2×103particles cm-3 and standard deviation 4.9×103particles cm-3, exhibiting an increasing trend between 2008 and 2011 and a decreasing trend from 2013 to 2015. The particle number concentrations exhibit highest values in spring and summer (despite the increased precipitation) due to the high occurrence of nucleation-mode particles, which most likely are formed elsewhere and are transported to the observation station. Particle hygroscopicity measurements show that, independently of the air mass origin, the particles are mostly externally mixed with the more hydrophobic mode having a mean hygroscopic parameter κ of 0.1 while for the more hydrophilic mode κ is 0.35. The hygroscopicity of the smaller particles investigated in this work (i.e., particles having diameters of 35nm) appears to increase during the course of the nucleation events, reflecting a change in the chemical composition of the particles.

PMID: 29306164 [PubMed - as supplied by publisher]

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Selective separation of microalgae cells using inertial microfluidics.

Selective separation of microalgae cells using inertial microfluidics.

Bioresour Technol. 2017 Dec 21;252:91-99

Authors: Syed MS, Rafeie M, Vandamme D, Asadnia M, Henderson R, Taylor RA, Warkiani ME

Abstract
Microalgae represent the most promising new source of biomass for the world's growing demands. However, the biomass productivity and quality is significantly decreased by the presence of bacteria or other invading microalgae species in the cultures. We therefore report a low-cost spiral-microchannel that can effectively separate and purify Tetraselmis suecica (lipid-rich microalgae) cultures from Phaeodactylum tricornutum (invasive diatom). Fluorescent polystyrene-microbeads of 6 μm and 10 μm diameters were first used as surrogate particles to optimize the microchannel design by mimicking the microalgae cell behaviour. Using the optimum flowrate, up to 95% of the P. tricornutum cells were separated from the culture without affecting the cell viability. This study shows, for the first time, the potential of inertial microfluidics to sort microalgae species with minimal size difference. Additionally, this approach can also be applied as a pre-sorting technique for water quality analysis.

PMID: 29306136 [PubMed - as supplied by publisher]

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Development and psychometric testing of a Clinical Reasoning Evaluation Simulation Tool (CREST) for assessing nursing students' abilities to recognize and respond to clinical deterioration.

Development and psychometric testing of a Clinical Reasoning Evaluation Simulation Tool (CREST) for assessing nursing students' abilities to recognize and respond to clinical deterioration.

Nurse Educ Today. 2017 Dec 12;62:74-79

Authors: Liaw SY, Rashasegaran A, Wong LF, Deneen CC, Cooper S, Levett-Jones T, Goh HS, Ignacio J

Abstract
BACKGROUND: The development of clinical reasoning skills in recognising and responding to clinical deterioration is essential in pre-registration nursing education. Simulation has been increasingly used by educators to develop this skill.
OBJECTIVE: To develop and evaluate the psychometric properties of a Clinical Reasoning Evaluation Simulation Tool (CREST) for measuring clinical reasoning skills in recognising and responding to clinical deterioration in a simulated environment.
DESIGN: A scale development with psychometric testing and mixed methods study.
PARTICIPANTS/SETTINGS: Nursing students and academic staff were recruited at a university.
METHOD: A three-phase prospective study was conducted. Phase 1 involved the development and content validation of the CREST; Phase 2 included the psychometric testing of the tool with 15 second-year and 15 third-year nursing students who undertook the simulation-based assessment; Phase 3 involved the usability testing of the tool with nine academic staff through a survey questionnaire and focus group discussion.
RESULTS: A 10-item CREST was developed based on a model of clinical reasoning. A content validity of 0.93 was obtained from the validation of 15 international experts. The construct validity was supported as the third-year students demonstrated significantly higher (p<0.001) clinical reasoning scores than the second-year students. The concurrent validity was also supported with significant positive correlations between global rating scores and almost all subscale scores, and the total scores. The predictive validity was supported with an existing tool. The internal consistency was high with a Cronbach's alpha of 0.92. A high inter-rater reliability was demonstrated with an intraclass correlation coefficient of 0.88. The usability of the tool was rated positively by the nurse educators but the need to ease the scoring process was highlighted.
CONCLUSIONS: A valid and reliable tool was developed to measure the effectiveness of simulation in developing clinical reasoning skills for recognising and responding to clinical deterioration.

PMID: 29306102 [PubMed - as supplied by publisher]

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Nursing students' perceptions of a video-based serious game's educational value: A pilot study.

Nursing students' perceptions of a video-based serious game's educational value: A pilot study.

Nurse Educ Today. 2017 Dec 28;62:62-68

Authors: Johnsen HM, Fossum M, Vivekananda-Schmidt P, Fruhling A, Slettebø Å

Abstract
BACKGROUND: Despite an increasing number of serious games (SGs) in nursing education, few evaluation studies specifically address their educational value in terms of face, content, and construct validity.
OBJECTIVES: To assess nursing students' perceptions of a video-based SG in terms of face, content, and construct validity. In addition, the study assessed perceptions of usability, individual factors, and preferences regarding future use.
DESIGN: A pilot study was conducted.
SETTING AND PARTICIPANTS: An SG prototype was implemented as part of two simulation courses in nursing education: one for home health care and one for hospital medical-surgical wards. The SG aimed to teach clinical reasoning and decision-making skills to nursing students caring for patients with chronic obstructive pulmonary disease. A total of 249second-year nursing students participated in pilot testing of the SG.
METHOD: A paper-based survey was used to assess students' perceptions of the SG's educational value.
RESULTS: Overall, students from both simulation courses perceived the SG as educationally valuable and easy to use. No significant differences were found in perceptions of educational value between nursing students with previous healthcare experience versus those with none. However, significantly more students in the home healthcare simulation course indicated that the SG tested their clinical reasoning and decision-making skills. Students from both the medical-surgical and home healthcare simulation courses suggested that more video-based SGs should be developed and used in nursing education.
CONCLUSIONS: Overall, the survey results indicate that the participants perceived the SG as educationally valuable, and that the SG has potential as an educational tool in nursing education, especially in caring for patients with chronic diseases and in home healthcare simulation. Showing a SG's educational value and user acceptance among nursing students may justify the development and application of more SGs in nursing education.

PMID: 29306100 [PubMed - as supplied by publisher]

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Simultaneous three-dimensional visualization of mineralized and soft skeletal tissues by a novel microCT contrast agent with polyoxometalate structure.

Simultaneous three-dimensional visualization of mineralized and soft skeletal tissues by a novel microCT contrast agent with polyoxometalate structure.

Biomaterials. 2017 Dec 22;159:1-12

Authors: Kerckhofs G, Stegen S, van Gastel N, Sap A, Falgayrac G, Penel G, Durand M, Luyten FP, Geris L, Vandamme K, Parac-Vogt T, Carmeliet G

Abstract
Biological tissues have a complex and heterogeneous 3D structure, which is only partially revealed by standard histomorphometry in 2D. We here present a novel chemical compound for contrast-enhanced microfocus computed tomography (CE-CT), a Hafnium-based Wells-Dawson polyoxometalate (Hf-POM), which allows simultaneous 3D visualization of mineralized and non-mineralized skeletal tissues, such as mineralized bone and bone marrow vasculature and adipocytes. We validated the novel contrast agent, which has a neutral pH in solution, by detailed comparison with (immuno)histology on murine long bones as blueprint, and showed that Hf-POM-based CE-CT can be used for virtual 3D histology. Furthermore, we quantified the 3D structure of the different skeletal tissues, as well as their spatial relation to each other, during aging and diet-induced obesity. We discovered, based on a single CE-CT dataset per sample, clear differences between the groups in bone structure, vascular network organization, characteristics of the adipose tissue and proximity of the different tissues to each other. These findings highlight the complementarity and added value of Hf-POM-based CE-CT compared to standard histomorphometry. As this novel technology provides a detailed 3D simultaneous representation of the structural organization of mineralized bone and bone marrow vasculature and adipose tissue, it will enable to improve insight in the interactions between these three tissues in several bone pathologies and to evaluate the in vivo performance of biomaterials for skeletal regeneration.

PMID: 29306094 [PubMed - as supplied by publisher]

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A model of gallbladder motility.

A model of gallbladder motility.

Comput Biol Med. 2017 Dec 26;93:139-148

Authors: Żulpo M, Balbus J, Kuropka P, Kubica K

Abstract
Impaired gallbladder motility leads to some clinical manifestations associated with its muscle contraction and/or the rate of filling with bile. To gain a better understanding of the possible reasons for different filling/emptying patterns we developed a mathematical model of the gallbladder that takes into account the kinetics of its filling and emptying and changes in the concentration of the accumulated bile. The model is based on four parameters responsible for the maximum speed of bile evacuation (Mg), pulsation of contractions (ω), the kinetic filling rate (kg) and the maximum bile mass accumulated in the gallbladder (mtotal). The model results were fitted to different clinical results describing gallbladder motility depending on the meal composition, patient's age and health condition (obesity and gallstones). Compatibility of the model results with the experimental data allows us to draw physiological conclusions. We found that different gallbladder emptying patterns may result from differences in the amplitude of contraction of gallbladder muscles (e.g. for various meal composition), differences in the rate of bile inflow (e.g. for obese patients during filling), and differences in gallbladder muscle pulsations (e.g. for lean patients during early gallbladder emptying). The model of gallbladder motility can facilitate identification of causes of disorders, help to explore complicated physiological pathways, and can be applied in etiology analysis or studies of observable clinical indicators.

PMID: 29306087 [PubMed - as supplied by publisher]

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Hybrid micro/nanostructural surface offering improved stress distribution and enhanced osseointegration properties of the biomedical titanium implant.

Hybrid micro/nanostructural surface offering improved stress distribution and enhanced osseointegration properties of the biomedical titanium implant.

J Mech Behav Biomed Mater. 2017 Nov 27;79:173-180

Authors: Hou PJ, Ou KL, Wang CC, Huang CF, Ruslin M, Sugiatno E, Yang TS, Chou HH

Abstract
OBJECTIVES: The aim of the present study was to investigate the surface characteristic, biomechanical behavior, hemocompatibility, bone tissue response and osseointegration of the optimal micro-arc oxidation surface-treated titanium (MST-Ti) dental implant.
MATERIALS AND METHODS: The surface characteristic, biomechanical behavior and hemocompatibility of the MST-Ti dental implant were performed using scanning electron microscope, finite element method, blood dripping and immersion tests. The mini-pig model was utilized to evaluate the bone tissue response and osseointegration of the MST-Ti dental implant in vivo. Data were analyzed by analysis of variance using the Student's t-test (P ≤ 0.05).
RESULTS: The hybrid volcano-like micro/nanoporous structure was formed on the surface of the MST-Ti dental implant. The hybrid volcano-like micro/nanoporous surface played an important role to improve the stress transfer between fixture, cortical bone and cancellous bone for the MST-Ti dental implant. Moreover, the MST-Ti implant was considered to have the outstanding hemocompatibility. In vivo testing results showed that the bone-to-implant contact (BIC) ratio significantly altered as the implant with micro/nanoporous surface. After 12 weeks of implantation, the MST-Ti dental implant group exhibited significantly higher BIC ratio than the untreated dental implant group. In addition, the MST-Ti dental implant group also presented an enhancing osseointegration, particularly in the early stages of bone healing.
CONCLUSION: It can be concluded that the micro-arc oxidation approach induced the formation of micro/nanoporous surface is a promising and reliable alternative surface modification for Ti dental implant applications.

PMID: 29306080 [PubMed - as supplied by publisher]

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Synthesis, molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors.

Synthesis, molecular docking and biological evaluation of some benzimidazole derivatives as potent pancreatic lipase inhibitors.

Bioorg Chem. 2017 Dec 28;76:478-486

Authors: Menteşe E, Yılmaz F, Emirik M, Ülker S, Kahveci B

Abstract
In this study, a new series of benzimidazole and bisbenzimidazole derivatives were prepared via the reaction of iminoester hydrochlorides and o-phenylenediamines and then screened for their lipase inhibition properties. Among the synthesized molecules, compounds 7a, 8a and 8c showed the best inhibitory effect against lipase enzyme with IC50 values of 1.72 ± 0.12 µM, 1.92 ± 0.28 and 0.98 ± 0.07 µM, respectively. Moreover, molecular modeling studies were performed in order to understand to the inhibitory activity of the molecules. Binding poses of the studied compounds were determined at the target sites using induced fit docking (IFD) algorithms.

PMID: 29306066 [PubMed - as supplied by publisher]

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CD38 is required for dendritic organisation in visual cortex and hippocampus.

CD38 is required for dendritic organisation in visual cortex and hippocampus.

Neuroscience. 2018 Jan 03;:

Authors: Nelissen TP, Bamford RA, Tochitani S, Akkus K, Kudzinskas A, Yokoi K, Okamoto H, Yamamoto Y, Burbach JPH, Matsuzaki H, Oguro-Ando A

Abstract
Morphological screening of mouse brains with known behavioural deficits can give great insight into the relationship between brain regions and their behaviour. Oxytocin- and CD38-deficient mice have previously been shown to have behavioural phenotypes, such as restrictions in social memory, social interactions, and maternal behaviour. CD38 is reported as an autism spectrum disorder (ASD) candidate gene and these behavioural phenotypes may be linked to ASD. To address whether these behavioural phenotypes relate to brain pathology and neuronal morphology, here we investigate the morphological changes in the CD38-deficient mice brains, with focus on the pathology and neuronal morphology of the cortex and hippocampus, using Nissl staining, immunohistochemistry, and Golgi staining. No difference was found in terms of cortical layer thickness. However, we found abnormalities in the number of neurons and neuron morphology in the visual cortex and dentate gyrus (DG). In particular, there were arborisation differences between CD38-/- and CD38+/+ mice in the apical dendrites of the visual cortex and hippocampal CA1 pyramidal neurons. The data suggests that CD38 is implicated in appropriate development of brain regions important for social behaviour.

PMID: 29306053 [PubMed - as supplied by publisher]

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Assessment of collagen fiber orientation dispersion in articular cartilage by small-angle X-ray scattering and diffusion tensor imaging: Preliminary results.

Assessment of collagen fiber orientation dispersion in articular cartilage by small-angle X-ray scattering and diffusion tensor imaging: Preliminary results.

Magn Reson Imaging. 2018 Jan 03;:

Authors: Tadimalla S, Tourell MC, Knott R, Momot KI

Abstract
Measurements of the orientational dispersion of collagen fibers in articular cartilage were made using diffusion tensor imaging (DTI) and small-angle X-ray scattering (SAXS) on matched bovine articular cartilage samples. Thirteen pairs of samples were excised from bovine knee joints; each pair was taken from neighboring locations in the same bone. One sample from each pair was used for DTI measurements and the other for SAXS measurements. Fractional anisotropy (FA) values were calculated from the DTI data both for the individual imaging voxels and for whole regions of interest (ROI). The FA values were used as a measure of fiber dispersion and compared to the ellipticities of the fiber orientation distributions obtained from SAXS. Neither the spatially-resolved FA values nor whole-ROI FA values showed any correlation with SAXS ellipticities. We attribute the lack of DTI-SAXS correlation to two principal factors: (1) the significant difference in the imaging resolution of the two techniques; and (2) the inherent limitations of both the SAXS data analysis methodology and the diffusion tensor model in the case of multi-modal fiber orientation distributions. We discuss how these factors could be overcome in future work.

PMID: 29306051 [PubMed - as supplied by publisher]

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Statistical analysis of non-coding RNA data.

Statistical analysis of non-coding RNA data.

Cancer Lett. 2018 Jan 03;:

Authors: He Q, Liu Y, Sun W

Abstract
With rapid progress in high-throughput genome technology, the study of noncoding RNA has arisen as a highly popular topic in biomedical research. Noncoding RNA plays fundamental roles in cell proliferation, cell differentiation and epigenetic regulation, and the study of noncoding RNA will yield novel insights into gene regulation and provide new clues for disease treatment. However, due to the large volume and diverse functions of noncoding RNAs, the analysis of these RNAs has proved to be a challenging task. In this review, we review the commonly used computational tools for the identification of noncoding RNAs, and discuss popular statistical tools for their analysis. Due to the large body of noncoding RNA classes, we will focus on the analysis of microRNA and long noncoding RNA, two of the most widely studied classes of noncoding RNAs. Specific examples are provided to show the context of the analysis. This review aims to provide up-to-date information on existing tools and methods for identifying and analyzing noncoding RNA.

PMID: 29306017 [PubMed - as supplied by publisher]

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The immune response of Mytilus edulis hemocytes exposed to Vibrio splendidus LGP32 strain: A transcriptomic attempt at identifying molecular actors.

The immune response of Mytilus edulis hemocytes exposed to Vibrio splendidus LGP32 strain: A transcriptomic attempt at identifying molecular actors.

Fish Shellfish Immunol. 2018 Jan 03;:

Authors: Tanguy M, Gauthier-Clerc S, Pellerin J, Danger JM, Siah A

Abstract
The marine mussel Mytilus edulis, tolerant to a wide range of environmental changes, combines a key role as a sentinel species for environmental monitoring programs and a significant economic importance. Mortality events caused by infective agents and parasites have not been described in mussels, which suggests an efficient immune system. This study aims at identifying the molecular mechanisms involved in the early immune responses M. edulis' hemocytes challenged with Vibrio splendidus LGP32 strain during 2, 4 and 6 h. A total of 149,296 assembled sequences has been annotated and compared to KEGG reference pathways. Several immune related sequences were identified such as Toll-Like receptors (TLRs), transcription factors, cytokines, protease inhibitors, stress proteins and sequences encoding for proteins involved in cell adhesion, phagocytosis, oxidative stress, apoptosis and autophagy. Differential gene expression clustered 10 different groups of transcripts according to kinetics of transcript occurrence. Sequences were assigned to biological process gene ontology categories. Sequences encoding for galectins, fibrinogen-related proteins, TLRs, MyD88, some antimicrobial peptides, lysosomal hydrolases, heat shock proteins and protease inhibitors, as well as proteins of oxidative stress and apoptosis were identified as differently regulated during the exposure to V. splendidus LGP32. The levels of candidate transcripts were quantified in M. edulis' hemocytes exposed to V. splendidus LGP32 and 7SHRW by using branched DNA technology. Transcripts encoding for inhibitor kappa B, inhibitor of apoptosis proteins, tumor protein D54, serine/threonine-proteine kinase SIK2 were identified as up-regulated in hemocytes exposed to both strains.

PMID: 29305989 [PubMed - as supplied by publisher]

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Mechanistic studies of the antibiofilm activity and synergy with antibiotics of isosorbide mononitrate.

Mechanistic studies of the antibiofilm activity and synergy with antibiotics of isosorbide mononitrate.

Eur J Pharm Sci. 2018 Jan 03;:

Authors: Hasan S, Albayaty YNS, Thierry B, Prestidge CA, Thomas N

Abstract
The use of nitric oxide (NO), a naturally occurring antimicrobial agent, as an alternative strategy to combat bacterial biofilms has recently gained considerable momentum in light of the global threat of emerging antibiotic resistance. While previous NO-based anti-biofilm approaches were aimed at killing bacteria cells within biofilms, NO has also been recently identified as a key mediator of biofilm dispersal, causing the release of cells from the biofilm community. This is of great interest towards the design of more effective anti-biofilm strategies but further studies are warranted to validate this concept. Therefore, in the present study we investigated whether a NO precursor, isosorbide mononitrate (ISMN) or its analogue D-isosorbide can induce bacteria cell dispersal from Staphylococcus aureus (S. aureus) biofilms and explored the potential synergy of ISMN and the antimicrobial compounds mupirocin and ciprofloxacin in biofilm eradication. We demonstrate that ISMN causes dispersal of S. aureus biofilm bacteria, particularly when exposed to high levels of drug. ISMN at 60mg/mL increased the number of colony forming units (CFU) (~3log10 and ~5log10) of planktonic bacteria after 6 and 24-h exposure respectively, compared to control biofilms. This suggests that ISMN induces the transition of sessile biofilm cells to free-swimming planktonic cells. In addition, ISMN exhibits synergistic effects against S. aureus biofilms with ciprofloxacin when tested above its minimum inhibitory concentration (MIC). Specifically, exposure to ISMN significantly enhanced the efficacy of ciprofloxacin by reducing the number of CFU (~3log10 or ~2log10) of biofilm-associated and planktonic bacteria respectively, compared to drug alone. Combined exposure to both ISMN and certain antimicrobial agents may therefore offer an innovative approach to control persistent biofilm and biofilm-associated infections.

PMID: 29305985 [PubMed - as supplied by publisher]

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Combining usability evaluations to highlight the chain that leads from usability flaws to usage problems and then negative outcomes.

Combining usability evaluations to highlight the chain that leads from usability flaws to usage problems and then negative outcomes.

J Biomed Inform. 2018 Jan 03;:

Authors: Watbled L, Marcilly R, Guerlinger S, Christian Bastien JM, Beuscart-Zéphir MC, Beuscart R

Abstract
Poor usability of health technology is thought to diminish work system performance, increase error rates and, potentially, harm patients. The present study (i) used a combination of usability evaluation methods to highlight the chain that leads from usability flaws to usage problems experienced by users and, ultimately, to negative patient outcomes, and (ii) validated this approach by studying two different discharge summary production systems. To comply with quality guidelines, the process of drafting and sending discharge summaries is increasingly being automated. However, the usability of these systems may modify their impact (or the absence thereof) in terms of production times and quality, and must therefore be evaluated. Here, we applied three successive techniques for usability evaluation (heuristic evaluation, user testing and field observation) to two discharge summary production systems (underpinned by different technologies). The systems' main usability flaws led respectively to an increase in the time need to produce a discharge summary and the risk of patient misidentification. Our results are discussed with regard to the possibility of linking the usability flaws, usage problems and the negative outcomes by successively applying three methods for evaluating usability (heuristic evaluation, user testing and in situ observations) throughout the system development life cycle.

PMID: 29305953 [PubMed - as supplied by publisher]

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Of mice and men: Traces of life in the death registries of the 1630 plague in Milano.

Of mice and men: Traces of life in the death registries of the 1630 plague in Milano.

J Proteomics. 2018 Jan 03;:

Authors: D'Amato A, Zilberstein G, Zilberstein S, Compagnoni BL, Righetti PG

Abstract
The death registries of the plague epidemic of 1630, stored at the Archivio di Stato of Milano, have been interrogated via the EVA film technology (ethyl vinyl acetate film studded with crushed strong anion and cation exchangers as well as C8 resins). The EVA diskettes have been left in contact with the lower right margins of 11 different pages pertaining to the peak months of the raging disease (June through end of September) for 60-90min and then the captured material, after elution and digestion, analysed by mass spectrometry. The main findings: 17 Yersiniaceae family proteins, 31 different human keratins, 22 unique mouse keratins, about 400 peptides from different bacterial strains, 58 human tissue proteins and 130 additional mouse and rat tissue proteins. In addition, >60 plant proteins (notably potato, corn, rice, carrot and chickpeas), likely representing the meagre meals of the scribes, contaminating the pages, were detected. The significance of these unique findings is amply illustrated in the body of the article.
SIGNIFICANCE: Archivists, historians, librarians usually explore the texts of ancient and modern manuscript in order to extract the meaning of the writing and understand the mood, feelings, political, philosophical and/or religious ideas therein expressed by the authors. With the present EVA methodology (the only one, at present, able to access our Cultural Heritage without damaging or contaminating it) we interrogate, instead, the support, be it paper, parchment, wood panel, cloth, canvas and the like, in order to extract invisible data, such as the presence of drugs, medicaments, infectious pathogens, human and environmental contaminants. Metabolites, proteins and peptides thus captured are then analysed via mass spectrometry. The unique data mined by this technology should considerably enlarge the (so far) restricted horizon of the writing exploration and add new insight on the environmental conditions in which such documents were produced as well as, importantly, on the health/pathological conditions of the authors. It is believed that the present technology, as here reported, will become the officially accepted one for exploring the world Cultural Heritage.

PMID: 29305937 [PubMed - as supplied by publisher]

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Gold nanoparticle should understand protein corona for being a clinical nanomaterial.

Gold nanoparticle should understand protein corona for being a clinical nanomaterial.

J Control Release. 2018 Jan 03;:

Authors: Charbgoo F, Nejabat M, Abnous K, Soltani F, Taghdisi SM, Alibolandi M, Thomas Shier W, Steele TWJ, Ramezani M

Abstract
Gold nanoparticles (AuNPs) have attracted great attention in biomedical fields due to their unique properties. However, there are few reports on clinical trial of these nanoparticles. In vivo, AuNPs face complex biological fluids containing abundant proteins, which challenge the prediction of their fate that is known as "bio-identity". These proteins attach onto the AuNPs surface forming protein corona that makes the first step of nano-bio interface and dictates the subsequent AuNPs fate. Protein corona formation even stealth active targeting effect of AuNPs. Manipulating the protein corona identity based on the researcher goal is the way to employ corona to achieve maximum effect in therapy or other applications. In this review, we provide details on the biological identity of AuNPs under various environmental- and/or physiological conditions. We also highlight how the particular corona can direct the biodistribution of AuNPs. We further discuss the strategies available for controlling or reducing corona formation on AuNPs surface and achieving desired effects using AuNPs in vivo by engineering protein corona on their surface.

PMID: 29305922 [PubMed - as supplied by publisher]

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Distribution of therapeutic proteins into thoracic lymph after intravenous administration is protein size-dependent and primarily occurs within the liver and mesentery.

Distribution of therapeutic proteins into thoracic lymph after intravenous administration is protein size-dependent and primarily occurs within the liver and mesentery.

J Control Release. 2018 Jan 03;:

Authors: Yadav P, McLeod VM, Nowell CJ, Selby LI, Johnston APR, Kaminskas LM, Trevaskis NL

Abstract
Therapeutic proteins can facilitate the targeting and treatment of lymphatic diseases (such as cancer metastases, infections and inflammatory diseases) since they are cleared via the lymphatics following interstitial (SC or IM) administration. However, therapeutic proteins are often administered intravenously (IV). Recently therapeutic proteins have been found to access the thoracic lymph in surprisingly high quantities after IV administration. The aim of this study was to determine, for the first time, the major sites of thoracic lymph access of therapeutic proteins, and the protein properties that enhance lymph access, after IV administration. In order to achieve this, novel methods were developed or optimized to collect hepatic, mesenteric or thoracic lymph from male SD rats. Four different sized PEGylated or non-PEGylated therapeutic proteins (native interferon α2b (IFN, 19kDa), PEGylated interferon α2b (IFN-PEG12, 31kDa), PEGylated interferon α2a (IFN-PEG40, 60kDa) or trastuzumab (150kDa)) were then administered via short IV infusion, and plasma and lymph concentrations of the proteins determined via ELISA. The recovery of the therapeutic proteins in the thoracic lymph duct, which collects lymph from most of the body, was significantly greater for trastuzumab, IFN-PEG40 and IFN-PEG12 (all >3% dose over 8h) when compared to native IFN (0.9% dose). Conversely, the thoracic lymph/plasma (L/P) concentration ratio and thus efficiency of extravasation and transport through the interstitium to lymph was highest for the smaller proteins IFN and IFN-PEG12 (at 90-100% vs 15-30% for trastuzumab and IFN-PEG40). The lower total recovery of IFN and IFN-PEG12 in thoracic lymph reflected more rapid systemic clearance and thus lower systemic exposure. For all therapeutic proteins, the majority (>80%) of lymph access occurred via the hepatic and mesenteric lymphatics. This lymphatic distribution pattern was supported by quantitative imaging of the lymph node distribution of IV administered Cy5 labelled trastuzumab. Optimizing the properties of IV administered therapeutic proteins represents a viable approach to better target and treat pathological states involving the lymphatics, particularly in the liver and mesentery. This includes cancer metastases, infections and inflammatory diseases. Successful development of the novel technique to collect hepatic lymph will also enable future work to evaluate tissue-specific lymph transport in health and disease.

PMID: 29305921 [PubMed - as supplied by publisher]

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Ophthalmic econazole hydrogels for the treatment of fungal keratitis.

Ophthalmic econazole hydrogels for the treatment of fungal keratitis.

J Pharm Sci. 2018 Jan 03;:

Authors: Díaz-Tomé V, Luaces-Rodríguez A, Silva-Rodríguez J, Blanco-Dorado S, García-Quintanilla L, Taboada JL, Blanco-Méndez J, Herranz M, Gil-Martínez M, Lamas MJ, González-Barcia M, Otero-Espinar FJ, Fernández-Ferreiro A

Abstract
Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest a-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterised in solution by 1D, 2D-NMR and molecular modelling. Econazole-a-cyclodextrin inclusion complex was included in two types of ocular hydrogels: a natural polysaccharides ion-sensitive hydrogel and a hyaluronic acid hydrogel. Both of them show no ocular irritation in the Hen's Egg Test on Chorioallantoic Membrane assay and a controlled econazole release over time. Permeability studies suggest hydrogels do not modify the econazole nitrate permeability through bovine cornea in comparison with an econazole-a-cyclodextrin inclusion complex solution. Finally, ocular biopermanence studies performed using Positron Emission Tomography show these hydrogels present a high retention time on the eye. Results suggest the developed formulations have a high potential as vehicles for the econazole topical ocular administration as fungal keratitis treatment.

PMID: 29305870 [PubMed - as supplied by publisher]

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Πληροφορίες

Κυριακή 7 Ιανουαρίου 2018

Abstract

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BACKGROUND

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Abstract

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Abstract

Abstract

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Graphical abstract

Δημοφιλείς αναρτήσεις