Κυριακή, 28 Μαΐου 2017

Deficiency of filaggrin regulates endogenous cysteine protease activity, leading to impaired skin barrier function

Summary

Background

Atopic dermatitis (AD) is a common inflammatory skin disorder, characterized by skin barrier defects and enhanced allergen priming. Null mutations in the filaggrin gene (FLG) are strongly associated with moderate to severe AD, but the pathways linking barrier dysfunction and cutaneous inflammation are still largely unknown.

Aim

To assess alteration of endogenous cysteine protease activity in FLG-deficient keratinocytes, and to determine whether the alteration in cysteine protease activity affects epidermal barrier function and associated gene and protein expression.

Methods

We established a stable FLG knockdown cell line, and reconstructed epidermal equivalents in vitro. Barrier function of the reconstructed epidermis, the barrier-associated genes and proteins, and the activity of endogenous cysteine proteases were tested. Inhibitors of cysteine proteases were used to further evaluate the role of endogenous cysteine proteases in epidermal barrier function.

Results

FLG knockdown induced impaired epidermal barrier function. Microarray, western blotting and fluorescence staining showed reduced expression of K10, ZO-1, E-cadherin, claudin-1 and occludin in FLG knockdown keratinocytes. Compared with cysteine protease activity in control cells, protease activity was dramatically enhanced in FLG knockdown keratinocytes. Furthermore, administration of cysteine protease inhibitors significantly recovered expression of K10 and tight junction proteins, and the barrier defect induced by FLG deficiency.

Conclusions

This is the first observation of elevated endogenous cysteine protease activity in FLG-deficient keratinocytes, which may play an important role in impaired barrier function in AD skin. Modulation of cysteine protease activity might be a novel therapeutic approach for AD treatment.



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Skin involvement as the first symptom of rapidly progressive ALK-positive systemic anaplastic large cell lymphoma

Summary

Systemic anaplastic large cell lymphomas (sALCLs) comprise a heterogeneous group of relatively rare T-cell non-Hodgkin lymphomas that are characterized by CD30 expression. Anaplastic lymphoma kinase (ALK)-positive ALCL is a type of sALCL that commonly involves lymph nodes and extranodal sites. Skin involvement usually presents as tumours, nodules and ulcers. We describe an unusual case of ALK-positive ALCL in an 11-year-old Chinese boy, who initially presented with skin eruption with rapid progression and poor prognosis. This case emphasizes the value of clinical factors to predict the prognosis of ALK-positive sALCL, and we recommend close collaboration between dermatologists, pathologists and haematologists/oncologists to assure the correct diagnosis and treatment.



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A recent-onset ulcerated nodular plaque on the scalp



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Preclinical pilot study monitoring topical drug penetration and dermal bioavailability of a peptidase inhibitor from different galenic formulations into pig dermis, using cutaneous microdialysis

Summary

Background

Cutaneous microdialysis (CM) is an ex vivo technique that allows study of tissue chemistry, including bioavailability of actual tissue concentration of unbound drug in the interstitial fluid of the body.

Aim

To test the penetration and dermal bioavailability of galenic formulations of the small-molecule IP10.C8, a dual-protease inhibitor of the dipeptidyl peptidase and aminopeptidase families.

Methods

Using CM, we tested the penetration and dermal bioavailability of IP10.C8 into the dermis and subcutis of pigs, and determined the tissue concentration of IP10.C8 enzymatically, using an enzyme activity assay (substrate Gly-Pro-pNA) and high performance liquid chromatography.

Results

Dermal bioavailability was enhanced by using microemulsion or the addition of the penetration enhancer oleic acid to a hydroxyethylcellulose (HEC) gel formulation. Dermal bioavailability was also enhanced when galenic formulations were prepared with higher pH (7.5 vs. 6.5) or higher drug concentration (5% vs. 1%) in HEC gel.

Conclusion

It seems possible, using CM for topical skin penetration testing in anaesthetized domestic pigs, to test the bioavailability of newly designed drugs. However, the experimental time is limited due to the anaesthesia, and is dependent on drug recovery. Validation of this technique for routine use is challenging, and more experiments are needed to validate this preclinical set-up.



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Topical capsaicin 8% for the treatment of neuropathic itch conditions



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Integration of reflectance confocal microscopy into clinical practice for the management of lentigo maligna



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Actinic keratosis. Or maybe not?



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Systematic review of the diagnosis of scabies in therapeutic trials

Summary

Human scabies (infestation with the mite Sarcoptes scabiei var hominis) causes a significant disease burden worldwide, yet there are no agreed diagnostic guidelines. We aimed to determine whether a consistent approach to diagnosing scabies has been used for published scabies therapeutic trials. The data sources used were the MEDLINE, Embase and Cochrane databases, from 1946 to 29 August 2013. Eligible studies were trials of therapeutic interventions against scabies in human subjects, published in English, enrolling patients with scabies, and using various therapeutic interventions. Language was a limitation of this study as some relevant trials published in languages other than English may have been excluded. Each study was reviewed by two independent authors, who assessed the clinical examination and testing approaches used for scabies diagnosis in the included studies. We found that of 71 included trials, 40 (56%) specified which clinical findings were used for diagnosis, which were predominantly rash, rash distribution, pruritus and mite burrows. Parasitological testing was used in 63% of trials (n = 45) and was used more frequently in clinic-based than in field studies. Nearly one-quarter of trials (24%, n = 17) did not define the diagnostic method used. Overall, the diagnostic approaches were poorly described, prohibiting accurate comparison of existing studies. This review further supports the need for consensus diagnostic guidelines for scabies.



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XIST RNA ISH as a Tool for Resolving Specimen Contamination Events

Abstract

The large number of manual steps involved in processing tissue creates many opportunities for specimen cross-contamination and carry-over defects, which may have serious medicolegal ramifications.1 In one study extraneous tissue was identified in 0.6% of slides, causing severe diagnostic difficulties in 0.4% of cases.1 As these events are not fully preventable, a quick, reliable, easily accessible method to resolve suspected contamination events is crucial.

This article is protected by copyright. All rights reserved.



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Long Noncoding RNAs as Biomarkers in Cancer

Long noncoding RNAs (lncRNAs) are a relatively well-characterized class of noncoding RNA (ncRNA) molecules, involved in the regulation of various cell processes, including transcription, intracellular trafficking, and chromosome remodeling. Their deregulation has been associated with the development and progression of various cancer types, the fact which makes them suitable as biomarkers for cancer diagnosis and prognosis. In recent years, detection of cancer-associated lncRNAs in body fluids of cancer patients has proven itself as an especially valuable method to effectively diagnose cancer. Cancer diagnosis and prognosis employing circulating lncRNAs are preferential when compared to classical biopsies of tumor tissues, especially due to their noninvasiveness, and have great potential for routine usage in clinical practice. Thus, this review focuses on summarizing the perspectives of lncRNAs as biomarkers in cancer, based on evaluating their expression profiles determined in body fluids of cancer patients.

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Exercise Metabolism in Nonobese Patients with Type 2 Diabetes Following the Acute Restoration of Normoglycaemia

This study investigated how acute restoration of normoglycaemia affected energy metabolism during exercise in nonobese patients with type 2 diabetes. Six subjects (mean ± SEM) aged 56.2 ± 2.7 years, with a BMI of 24.5 ± 1.5 kg/m2 and a VO2 peak of 28.7 ml/kg/min, attended the lab on two randomised occasions for a four-hour resting infusion of insulin or saline, followed by 30 minutes cycling at 50% VO2 peak. During the 4 h resting infusion, there was a greater () reduction in blood glucose in insulin treatment (INS) (from 11.2 ± 0.6 to 5.6 ± 0.1 mmol/l) than in saline treatment/control (CON) (from 11.5 ± 0.7 to 8.5 ± 0.6 mmol/l). This was associated with a lower () resting metabolic rate in INS (3.87 ± 0.17) than in CON (4.39 ± 0.30 kJ/min). During subsequent exercise, blood glucose increased significantly in INS from 5.6 ± 0.1 at 0 min to 6.3 ± 0.3 mmol/l at 30 min (), which was accompanied by a lower blood lactate response (). Oxygen uptake, rates of substrate utilization, heart rate, and ratings of perceived exertion were not different between trials. Insulin-induced normoglycaemia increased blood glucose during subsequent exercise without altering overall substrate utilization.

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Effect of Quasi-Isotropic Antenna Orientation on Indoor Multipath Propagation Characteristics in RSN Applications

In the RFID sensor networks (RSN), the orientations of the antennas used in the network nodes have a significant influence on the propagation characteristics. In this article, we investigated the effects of the two antennas’ orientation of different radiation and polarization on the multipath propagation characteristics. This study is evaluated in a typical indoor environment by computer simulations based on the three-dimensional (3D) ray-tracing method. This method is based on geometric optics and uniform diffraction theory and also it offers significant advantages in terms of accurate and comprehensive prediction of propagation characterization. The simulations have been performed at frequency 915 MHz and the propagation characteristics are compared in terms of received power level () and Root-Mean-Square (RMS) delay spread for a quasi-isotropic 3D cubic antenna with circular polarization and for an omnidirectional dipole with linear polarization in the LOS, NLOS, and OLOS scenarios.

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Osteolytic lesions: osteitis fibrosa cystica in the setting of severe primary hyperparathyroidism

A 58-year-old female patient presented with several weeks history of significant bilateral knee pain. Initial knee radiographs demonstrated lucencies of the bony cortex while extensive osteolytic lesions on a routine chest radiograph were suggestive of multiple myeloma or bony metastases. Biochemical investigation revealed primary hyperparathyroidism with renal insufficiency. A parathyroid adenoma was demonstrated on a neck ultrasound and sestamibi scan and subsequently confirmed by histology. We illustrate a case of primary hyperparathyroidism with osteitis fibrosa cystica and brown tumours which were initially mistaken for malignant disease.



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Streptococcus bovis prosthetic valve endocarditis associated with silent colonic carcinoma

A 75-year-old woman was admitted to our hospital with a 3-month history of fever. Of note, she had a bioprosthetic mitral valve replacement 1 year prior to admission. Streptococcus bovis was isolated from three sets of blood cultures. An echocardiogram showed a flickering mass attached to the bioprosthesis. Her blood culture became sterile by the fourth day of ceftriaxone therapy. In spite of the absence of gastrointestinal symptoms, screening colonoscopy revealed an invasive colonic adenocarcinoma. The association linking S. bovis endocarditis and colonic tumours is well recognised. However, despite early reports of this association by Klein et al in 1979, a large number of practising physicians remain unaware of this phenomenon. This lack of awareness results in lost opportunities for early diagnosis and, consequently, improved outcome in such patients. Our report emphasises this association in an area with a low incidence of S. bovis endocarditis.



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Ichthyosis linearis circumflexa with bamboo hair: challenges in the diagnosis and management

A 15-year-old boy had persistent and refractory erythroderma since early childhood. His parents noticed polycyclic skin lesions and hair fragility around the age of 5 years. He was treated by a local untrained practitioner for more than 3 years without any significant improvement, and he developed weight gain, thinning of skin, muscle weakness and growth retardation. He was evaluated in 2015 and found to have iatrogenic Cushing’s disease with severe skeletal complications and pituitary-adrenal-gonadal suppression, which persisted despite gradual withdrawal of steroids.



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A rare case of bilateral lens dislocations

Description

A 39-year-old man presented to our hospital following transfer from a rural site with an acute right eye anterior lens dislocation following a traumatic blow to the head. He had been hit 7 days prior and had suffered gradual vision loss in the right eye since then. Visual acuity was counting fingers at 1 m in his right eye and perception of light in his left eye. He had an intraocular pressure (IOP) of 50 mm Hg in his right eye on arrival. He had a CT head non-contrast performed. The axial (figure 1) and sagittal (figures 2 and 3) slices demonstrated a right eye anterior lens dislocation and a left eye posterior lens dislocation. The left eye had been injured 3 years prior and the patient had not sought treatment for it at the time. On examination, the left eye was found to...



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The authors respond to: "Questions on analysis of firearm injuries study" [Letters]



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Disparities in infant hospitalizations in Indigenous and non-Indigenous populations in Quebec, Canada [Research]

BACKGROUND:

Infant mortality is higher in Indigenous than non-Indigenous populations, but comparable data on infant morbidity are lacking in Canada. We evaluated disparities in infant morbidities experienced by Indigenous populations in Canada.

METHODS:

We used linked population-based birth and health administrative data from Quebec, Canada, to compare hospitalization rates, an indicator of severe morbidity, in First Nations, Inuit and non-Indigenous singleton infants (< 1 year) born between 1996 and 2010.

RESULTS:

Our cohort included 19 770 First Nations, 3930 Inuit and 225 380 non-Indigenous infants. Compared with non-Indigenous infants, all-cause hospitalization rates were higher in First Nations infants (unadjusted risk ratio [RR] 2.05, 95% confidence interval [CI] 1.99–2.11; fully adjusted RR 1.43, 95% CI 1.37–1.50) and in Inuit infants (unadjusted RR 1.96, 95% CI 1.87–2.05; fully adjusted RR 1.37, 95% CI 1.24–1.52). Higher risks of hospitalization (accounting for multiple comparisons) were observed for First Nations infants in 12 of 16 disease categories and for Inuit infants in 7 of 16 disease categories. Maternal characteristics (age, education, marital status, parity, rural residence and Northern residence) partly explained the risk elevations, but maternal chronic illnesses and gestational complications had negligible influence overall. Acute bronchiolitis (risk difference v. non-Indigenous infants, First Nations 37.0 per 1000, Inuit 39.6 per 1000) and pneumonia (risk difference v. non-Indigenous infants, First Nations 41.2 per 1000, Inuit 61.3 per 1000) were the 2 leading causes of excess hospitalizations in Indigenous infants.

INTERPRETATION:

First Nations and Inuit infants had substantially elevated burdens of hospitalizations as a result of diseases of multiple systems. The findings identify substantial unmet needs in disease prevention and medical care for Indigenous infants.



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Record number of unmatched medical graduates [News]



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Antidepressant discontinuation syndrome [Practice]



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Increased rate of early smoking in children and adolescents with attention-deficit/hyperactivity disorder [Letters]



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Atypical presentation of syphilis as an aphthous ulcer [Practice]



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Cannabis legislation fails to protect Canadas youth [Editorial]



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Ectopic tooth: an unusual cause of headache [Practice]



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More on firearm injuries among children and youth [Letters]



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Two documents [Humanities]



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Is Ontarios youth pharmacare proposal just a symbolic gesture? [News]



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Questions on analysis of firearm injuries study [Letters]



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Is police-public health collaboration an oxymoron? [News]



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Novel dermoscopic findings in mudi-chood disease – a case report



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Title Page/Sections Editors

Publication date: July 2017
Source:Biochimica et Biophysica Acta (BBA) - Gene Regulatory Mechanisms, Volume 1860, Issue 7





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Hassall's corpuscles in the fine-needle aspiration cytology of pediatric ectopic thymic tissue



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Ψ Multiple eccrine spiradenomas with a zosteriform pattern—Report of a rare case diagnosed on fine needle aspiration cytology



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Biphasic axillary synovial sarcoma diagnosed by preoperative fine-needle aspiration cytology

Synovial sarcoma (SS) is a soft-tissue sarcoma which usually occurs in lower extremities. Less than 20 cases of SS located in shoulder or axillary region have been reported, and these studies describe histopathological features. We report a case of axillary SS diagnosed by fine-needle aspiration cytology, immunocytochemistry, and molecular techniques performed on cytology smears. A 48-year-old woman presented with a palpable and well-defined axillary mass which measured 4 cm. On-site smears showed high cellularity with spindle cells, and a mesenchymal tumor was suspected. Definitive cytological analysis showed cells with ovoid- or comma-shaped nuclei arranged in loose sheets and fascicles, associated with naked nuclei and isolated cells. Mitotic count was 2 mitoses/HPF. Immunocytochemical studies showed vimentin and focal CK AE1-AE3 positivity. A PCR was performed and the specific translocation t(X;18) was detected. The lesion was excised and the diagnosis of biphasic SS was confirmed. The identification of SS on cytology specimens is difficult and differential diagnosis is broad. Complementary studies are necessary and they can be performed on FNA smears or cell blocks.



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Upper urinary tract washings outperform voided urine specimens to detect upper tract high-grade urothelial carcinoma

Background

Cytological examination of voided urine (VU) can reliably diagnose high-grade urothelial carcinoma (HGUC) of the lower urinary tract, but its value in the diagnosis of upper tract HGUC (UTHGUC) is less well-established. To clarify the utility of VU in the setting of UTHGUC, we examined urinary specimens from patients with UTHGUC on follow-up surgical pathology.

Methods

52 VU specimens (47 patients) with subsequent biopsy-proven UTHGUC were identified over a 12-year period; 32 had a corresponding upper tract urinary washing (UW) specimen. Patients with concurrent bladder HGUC were excluded. The diagnoses of VU specimens were tabulated and compared to those of UW specimens.

Results

Three UW specimens had a less severe diagnosis, 8 had the same diagnosis, and 21 had a more severe diagnosis than the corresponding VU specimen from the same patient. Significantly more UW specimens demonstrated high-risk features as compared with VU specimens (P = .003). In specimens with atypia, a definitive diagnosis of HGUC was made significantly more often on UW vs. VU specimens (P = .003).

Conclusions

Among patients with confirmed UTHGUC, 50% of preceding VU specimens demonstrated high-grade features compared to almost 90% of UW specimens. Though VU cytology shows atypia in the majority of cases, it performs inferiorly to UW for the detection of UTHGUC.



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Sometimes pain originating from a non-odontogenic pathologic condition is mistaken as endodontic illness, leading to misdiagnosis.

http://otorhinolaryngology-crete.blogspot.com/2017/05/adenoid-cystic-carcinoma-of-maxillary.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

Subclinical hypothyroidism (SCH) has been associated with atherosclerosis and increased risk of ischemic stroke.

http://otorhinolaryngology-crete.blogspot.com/2017/05/subclinical-hypothyroidism-and-risk-of.html

Alexandros Sfakianakis
Anapafseos 5 . Agios Nikolaos
Crete.Greece.72100
2841026182
6948891480

The global state of psoriasis disease epidemiology: a workshop report

Summary

The International Psoriasis Council, a global nonprofit organization dedicated to innovation across the full spectrum of psoriasis, led a symposium to discuss the current state of psoriasis epidemiology and to introduce the vision and development of a Global Psoriasis Atlas. The symposium was held on 9 September 2015 at the 45th annual meeting of the European Society for Dermatological Research, Rotterdam, the Netherlands. Collectively, these presentations highlighted challenges associated with assessing psoriasis epidemiology and emphasized the urgent need for an authoritative resource to clarify psoriasis disease burden on a global scale.



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Atenolol Versus Propranolol for Treatment of Infantile Hemangiomas During the Proliferative Phase: A Retrospective Noninferiority Study

Abstract

Background/Objectives

The nonselective beta-blocker propranolol is the current criterion standard for treatment of infantile hemangiomas (IHs) and the first therapy that the U.S. Food and Drug Administration has approved for the condition, but concern about adverse effects, such as bronchospasm, hypoglycemia, and sleep disturbances, has sparked interest in the use of alternative agents such as the selective β1 antagonist atenolol. Our aim was to compare the efficacy and adverse effect profiles of atenolol with those of propranolol in the treatment of IHs in a retrospective noninferiority trial.

Methods

Twenty-seven children with IHs treated with atenolol according to the Cleveland Clinic foundation's standardized clinical assessment and management plan (SCAMP) met inclusion criteria and were compared with a matched group of 53 children with IHs treated with propranolol. Three reviewers assessed response to therapy using a modified version of the previously validated Hemangioma Activity Score (HAS).

Results

The mean change in HAS was −2.94 ± 1.20 for patients treated with atenolol and −2.96 ± 1.42 for those treated with propranolol. There was no statistically significant difference in pre- and posttreatment modified HAS scores between the two groups (p = 0.60). There was no significant difference in the overall rate of adverse effects (p = 0.10), although 11% of patients treated with propranolol experienced reactive airway symptoms, whereas this was not seen in any of the patients treated with atenolol.

Conclusion

Our study supports previous findings that atenolol is at least as effective as propranolol for treatment of IHs and poses less risk of bronchospasm. Our SCAMP proposes guidelines for dosing and monitoring parameters.



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The global state of psoriasis disease epidemiology: a workshop report

Summary

The International Psoriasis Council, a global nonprofit organization dedicated to innovation across the full spectrum of psoriasis, led a symposium to discuss the current state of psoriasis epidemiology and to introduce the vision and development of a Global Psoriasis Atlas. The symposium was held on 9 September 2015 at the 45th annual meeting of the European Society for Dermatological Research, Rotterdam, the Netherlands. Collectively, these presentations highlighted challenges associated with assessing psoriasis epidemiology and emphasized the urgent need for an authoritative resource to clarify psoriasis disease burden on a global scale.



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BacterioFiles 295 - Fly Ferries Fungus Feebleness

bf295fly.jpg

This episode: Fungus-eating flies transfer viruses that help make fungi less harmful to plants!

(7.8 MB, 8.5 minutes)

Show notes: 


...

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Memory

Memory: 1. The ability to recover information about past events or knowledge. 2. The process of recovering information about past events or knowledge. 3. Cognitive reconstruction. The brain engages in a remarkable reshuffling process in an attempt to extract what is general and what is particular about each passing moment.

Memory may be divided into short-term (also known as working or recent memory) and long-term memory. Short-term memory recovers memories of recent events, while long-term memory is concerned with recalling the more distant past.

Some disorders, such as Alzheimer's disease, damage the cognitive systems that control memory. Usually long-term memory is retained while short-term memory is lost; conversely, memories may become jumbled, leading to mistakes in recognizing people or places that should be familiar.

See also: Explicit memory; Implicit memory.

.

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

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Simplified clinical algorithm for identifying patients eligible for immediate initiation of antiretroviral therapy for HIV (SLATE): protocol for a randomised evaluation

Introduction

African countries are rapidly adopting guidelines to offer antiretroviral therapy (ART) to all HIV-infected individuals, regardless of CD4 count. For this policy of ‘treat all’ to succeed, millions of new patients must be initiated on ART as efficiently as possible. Studies have documented high losses of treatment-eligible patients from care before they receive their first dose of antiretrovirals (ARVs), due in part to a cumbersome, resource-intensive process for treatment initiation, requiring multiple clinic visits over a several-week period.

Methods and analysis

The Simplified Algorithm for Treatment Eligibility (SLATE) study is an individually randomised evaluation of a simplified clinical algorithm for clinicians to reliably determine a patient’s eligibility for immediate ART initiation without waiting for laboratory results or additional clinic visits. SLATE will enrol and randomise (1:1) 960 adult, HIV-positive patients who present for HIV testing or care and are not yet on ART in South Africa and Kenya. Patients randomised to the standard arm will receive routine, standard of care ART initiation from clinic staff. Patients randomised to the intervention arm will be administered a symptom report, medical history, brief physical exam and readiness assessment. Patients who have positive (satisfactory) results for all four components of SLATE will be dispensed ARVs immediately, at the same clinic visit. Patients who have any negative results will be referred for further clinical investigation, counselling, tests or other services prior to being dispensed ARVs. After the initial visit, follow-up will be by passive medical record review. The primary outcomes will be ART initiation ≤28 days and retention in care 8 months after study enrolment.

Ethics and dissemination

Ethics approval has been provided by the Boston University Institutional Review Board, the University of the Witwatersrand Human Research Ethics Committee (Medical) and the KEMRI Scientific and Ethics Review Unit. Results will be published in peer-reviewed journals and made widely available through presentations and briefing documents.

Trial registration

NCT02891135



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Low Hemoglobin among Pregnant Women in Midwives Practice of Primary Health Care, Jatinangor, Indonesia: Iron Deficiency Anemia or β-Thalassemia Trait?

Low hemoglobin (Hb) or anemia is common among pregnant women in developing countries which may cause adverse pregnancy outcomes and maternal deaths. Our study aimed to assess Hb level measured by midwives in primary health care facility at rural area of Jatinangor, Indonesia, and to explore whether the anemia was due to iron deficiency (IDA) or β-thalassemia trait (β-TT). Pregnant women () had finger prick test for Hb level during a regular antenatal care examination from October to November 2016. Hb level by finger prick test was compared with venous blood, measured by complete blood count (CBC). Indices including MCV and MCH and indices of Shine & Lal, Mentzer, Srivastava, Engels & Frase, Ehsani, and Sirdah were analyzed to differentiate anemia due to IDA and anemia due to suspect β-TT. HbA2 was measured to confirm β-TT. Anemic pregnant women were found in 86.7% by finger prick test compared to 21.9% () by CBC. The prevalence of β-TT in our study was 5.7%. Hb measurement among pregnant women in low resource area is highly important; however, finger prick test in this study showed a high frequency of anemia which may lead to iron oversupplementation. A standard CBC is encouraged; MCV and MCH would help midwives to identify β-TT.

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DJC Suppresses Advanced Glycation End Products-Induced JAK-STAT Signaling and ROS in Mesangial Cells

The antidiabetic properties and anti-inflammatory effects of Danzhi Jiangtang Capsules (DJC) have been demonstrated in clinical and laboratory experiments. In this study, we explored whether DJC can ameliorate advanced glycation end products- (AGEs-) mediated cell injury and the precise mechanisms of DJC in treating diabetic nephropathy (DN). Western blot analysis was employed to assess the expressions of iNOS, COX2, and SOCS and the phosphorylation of JAK2, STAT1, and STAT3 in glomerular mesangial cells (GMCs) after treatment with DJC. TNF-α, IL-6, and MCP-1 were determined using double-antibody sandwich ELISA. ROS and NADPH oxidase activity were measured by DCFH-DA assay and lucigenin-enhanced chemiluminescence, respectively. DJC significantly reversed the AGEs-induced expression of COX2 and iNOS. Moreover, DJC inhibited the AGEs-induced JAK2-STAT1/STAT3 activation, resulting in the inhibition of inflammatory cytokines such as IL-6, MCP-1, and TNF-α in a concentration-dependent manner. The ability of DJC to suppress STAT activation was also verified by the observation that DJC significantly increased the SOCS3 protein level. DJC reversed the AGEs-induced accumulation of ROS and NADPH oxidase activity, thus confirming that DJC possesses antioxidant activity. The results suggest that the anti-inflammatory effects of DJC in GMCs may be due to its ability to suppress the JAK2-STAT1/STAT3 cascades and reduce ROS production.

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Throat cancer survivors speak again, a burp does the trick - Daily News & Analysis


Daily News & Analysis

Throat cancer survivors speak again, a burp does the trick
Daily News & Analysis
Babies learn to burp even before they begin to talk. For throat cancer survivors who have lost their larynx (voice box) to cancer, it is this instinct of a baby that they are reminded to go back to and produce a sound. The technique is neither simple ...



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To your health: Nicotine dependence - Viet Nam News


Viet Nam News

To your health: Nicotine dependence
Viet Nam News
Smoking is a major cause of cancers of the esophagus, larynx, throat and mouth and is also connected to cancers of the bladder, pancreas, kidney, cervix and stomach. - Skin structure changes, causing premature aging and wrinkles. - Increased ...
Bamisile: Smoking is the worst invention of modern eraGuardian (blog)

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All These Cancer Screenings Probably Won't Save Your Life - Daily Beast


Daily Beast

All These Cancer Screenings Probably Won't Save Your Life
Daily Beast
Other cancers are harder to prevent, like those of the prostate, thyroid, and breast. The reason, as explained by Gilbert Welch, a professor of medicine at Dartmouth, is best explained using a barnyard analogy. Imagine, writes Welch, that three animals ...

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An updated phylogeny of Sordariomycetes based on phylogenetic and molecular clock evidence

Abstract

The previous phylogenies of Sordariomycetes by M.E. Barr, O.E. Eriksson and D.L. Hawksworth, and T. Lumbsch and S. Huhndorf, were mainly based on morphology and thus were somewhat subjective. Later outlines by T. Lumbsch and S. Huhndorf, and Maharachchikumbura and co-authors, took into account phylogenetic evidence. However, even these phylogenetic driven arrangements for Sordariomycetes, were somewhat subjective, as the arrangements in trees depended on many variables, such as number of taxa, different gene regions and methods used in the analyses. What is needed is extra evidence to help standardize ranking in the fungi. Estimation of divergence times using molecular clock methods has been proposed for providing additional rational for higher ranking of taxa. Thus, in Sordariomycetes, a divergence period (i.e. 200–300 MYA) can be used as criteria to judge when a group of related taxa evolved and what rank they should be given. In this paper, we provide an updated classification of accepted subclasses, orders of Sordariomycetes and use divergence times to provide additional evidence to stabilize ranking of taxa in the class. We point out and discuss discrepancies where the phylogenetic tree conflicts with the molecular clock.



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A case of ulcerative colitis with squamous cell carcinomas and multiple foci of squamous dysplasia

Squamous cell carcinoma (SqCC) in ulcerative colitis (UC) is rare. A 38 year-old Japanese woman, who suffered from left-sided UC for 18 years, underwent total colectomy due to SqCCs in the rectum and the sigmoid colon. They were well differentiated SqCC, and metastasis was found in the paracolic lymph nodes. Multiple small foci of squamous dysplasia (SD) were noted in the rectal mucosa. Glandular dysplasia was not found. TP53 was not detected in SD. Approximately 40% of cells were immunostained with TP53 in SqCC, however no mutation was found in TP53 gene. Human papilloma virus and Epstein Barr virus were negative in SD and SqCCs. The patient is free of the disease at one and half years after surgery and chemotherapy. SD may be a precursor of SqCC. It appeared that TP53 does not play a vital role in the development of SqCCs in the current case. Careful attention should be paid to SD in UC patients. Viral infection may need to be examined. The pathogenesis of SqCC in patients of UC needs to be elucidated.



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Lives Lived: Maurice Shenkier, 85 - The Globe and Mail


Lives Lived: Maurice Shenkier, 85
The Globe and Mail
Larynx cancer left Mo with a raspy voice from the age of 51. When asked how he got such a sexy voice, his answers varied from shark attack to parachuting accident to high-altitude frostbite. The stories often worked as he generally exuded an element of ...



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All These Cancer Screenings Probably Won't Save Your Life - Daily Beast


Daily Beast

All These Cancer Screenings Probably Won't Save Your Life
Daily Beast
Other cancers are harder to prevent, like those of the prostate, thyroid, and breast. The reason, as explained by Gilbert Welch, a professor of medicine at Dartmouth, is best explained using a barnyard analogy. Imagine, writes Welch, that three animals ...



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Cost of elective percutaneous coronary intervention in Malaysia: a multicentre cross-sectional costing study

Objectives

Limitations in the quality and access of cost data from low-income and middle-income countries constrain the implementation of economic evaluations. With the increasing prevalence of coronary artery disease in Malaysia, cost information is vital for cardiac service expansion. We aim to calculate the hospitalisation cost of percutaneous coronary intervention (PCI), using a data collection method customised to local setting of limited data availability.

Design

This is a cross-sectional costing study from the perspective of healthcare providers, using top-down approach, from January to June 2014. Cost items under each unit of analysis involved in the provision of PCI service were identified, valuated and calculated to produce unit cost estimates.

Setting

Five public cardiac centres participated. All the centres provide full-fledged cardiology services. They are also the tertiary referral centres of their respective regions.

Participants

The cost was calculated for elective PCI procedure in each centre. PCI conducted for urgent/emergent indication or for patients with shock and haemodynamic instability were excluded.

Primary and secondary outcome measures

The outcome measures of interest were the unit costs at the two units of analysis, namely cardiac ward admission and cardiac catheterisation utilisation, which made up the total hospitalisation cost.

Results

The average hospitalisation cost ranged between RM11 471 (US$3186) and RM14 465 (US$4018). PCI consumables were the dominant cost item at all centres. The centre with daycare establishment recorded the lowest admission cost and total hospitalisation cost.

Conclusions

Comprehensive results from all centres enable comparison at the levels of cost items, unit of analysis and total costs. This generates important information on cost variations between centres, thus providing valuable guidance for service planning. Alternative procurement practices for PCI consumables may deliver cost reduction. For countries with limited data availability, costing method tailored based on country setting can be used for the purpose of economic evaluations.

Registration

Malaysian MOH Medical Research and Ethics Committee (ID: NMRR-13-1403-18234 IIR).



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Extracardiac Imaging of Infective Endocarditis

Abstract

Purpose of Review

This review analyzes recent studies evaluating the diagnostic and therapeutic impacts of systematic extracardiac imaging techniques in patients with suspected or proven infective endocarditis.

Recent Findings

Extracardiac imaging techniques are more and more frequently used to establish infective endocarditis (IE) diagnosis in doubtful situations. They also help in evaluating the risk-benefit balance of therapeutic strategies and particularly valvular surgery which is performed in approximately 50% of patients. Latest research underlines the high frequency of asymptomatic lesions found, and a different advantage-disadvantage profile for each of these techniques.

Summary

Extracardiac imaging techniques are helpful in doubtful situations and may be considered in other situations. Their interest for improving patients' prognosis remains to be established.



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Computer-assisted orthognathic surgery: evaluation of mandible registration accuracy and report of the first clinical cases of navigated sagittal split ramus osteotomy

Intraoperative navigation is a helpful tool in complex anatomical regions or procedures. The mobility of the mandible in relation to the skull base limits the use of navigation tools on the lower jaw if the reference device is installed on the forehead. A new workflow that allows navigation-assisted sagittal split osteotomy in orthognathic surgery using a separate non-invasive mandibular registration technique has been developed. An evaluation of accuracy in different anatomical regions and with different registration techniques was performed on skull models and skulls with movable mandibles.

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28/05/2017 - Radioterapia oncologica, gli studi della Fondazione a Vienna - Primonumero.it


Primonumero.it

28/05/2017 - Radioterapia oncologica, gli studi della Fondazione a Vienna
Primonumero.it
... l'utilizzo della radioterapia stereotassica per le metastasi extracraniche e di tecniche di radioterapia sempre più evolute per il trattamento delle neoplasie cerebrali, del distretto testa-collo, della mammella, dei tumori gastro-intestinali e per ...

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More patients presenting with HPV-associated oral cancers in Lubbock, TX

Source: lubbockonline.com Author: Ellysa Harris Detecting oral cancers in patients in their 50s and 60s has never been uncommon. But local […]

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The effects of alpha 1-adrenoceptor blockade and angiotensin converting enzyme inhibition on central and brachial blood pressure and vascular reactivity: the doxazosin–ramipril study

Abstract

We aimed to study whether inhibition of the renin–angiotensin–aldosterone system has effects on vascular structure and function beyond the effects on blood pressure reduction alone. Patients with mild-to-moderate hypertension (n = 61, age 54 ± 12 years, 34% women) received the angiotensin converting enzyme inhibitor ramipril 10 mg or the alpha 1-adrenoceptor blocker doxazosin 8 mg double-blind for 12 weeks. Aortic blood pressure, pulse wave velocity, and augmentation index were assessed by applanation tonometry. Endothelial function was studied by forearm post-ischemic flow mediated vasodilatation and by pulse wave analysis with beta 2-adrenoceptor agonist stimulation. Skin microvascular reactivity was assessed by laser Doppler fluxmetry and iontophoresis. Treatment with doxazosin or ramipril reduced aortic and brachial blood pressures (all P < 0.001), with greater reductions in aortic than brachial systolic blood pressures (P = 0.021) and aortic/brachial pulse pressure ratio (P = 0.005). Compared to doxazosin, ramipril reduced carotid-femoral and carotid-radial pulse wave velocity (both P < 0.05). Forearm endothelial dependent and independent vasodilatation, assessed by post-ischemic flow mediated vasodilatation and glyceryl trinitrate, and by pulse wave analysis remained unchanged by both doxazosin and ramipril. In addition, skin microvascular endothelial dependent (acetylcholine) and independent vasodilatation (sodium nitroprusside) remained unchanged. In conclusion, ramipril reduced indices of aortic stiffness, suggesting that angiotensin converting enzyme inhibitor therapy may have effects beyond blood pressure reduction. However, treatment did not appear to influence endothelial function. Evidence of endothelial dysfunction and its possible improvement by antihypertensive treatment might require more advanced hypertension.

This study is registered at ClinicalTrials.gov (NCT02901977) and at EudraCT (# 2007-000631-25).



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Platelet reactivity and clinical outcomes in patients using CYP3A4-metabolized statins with clopidogrel in percutaneous coronary intervention

Abstract

Statins are primarily metabolized by cytochrome P450 3A4 (CYP3A4), which reduces clopidogrel to its active metabolite. Recent studies suggest that CYP3A4-metabolized statins attenuate clopidogrel's anti-aggregatory effect on platelets. We aimed to assess the impact of concomitant CYP3A4-metabolized statin and clopidogrel use on antiplatelet activity and clinical outcomes in patients undergoing percutaneous coronary intervention (PCI). We enrolled 1187 patients from the HOST–ASSURE trial with platelet reactivity unit (PRU) values at both baseline and 1 month. Patients were assigned to the CYP3A4-metabolized statin group (group A, n = 725) or non-CYP3A4-metabolized statin group (group B, n = 462) according to type of statin used. Co-primary outcomes were the differences between PRU at baseline and 1 month and the composite of cardiovascular death, recurrent myocardial infarction, stent thrombosis, revascularization, and cerebrovascular accident. We found that follow-up PRU values did not change in group A and decreased significantly in group B (mean difference: −15 ± 79, p < 0.001) in both the crude and matched cohorts. Patients with a high PRU value at baseline, irrespective of statin type, had a significant reduction in mean PRU difference (group A, −62 ± 78, p < 0.001; group B, −59 ± 69, p < 0.001) in both the crude and matched cohorts. The composite of clinical events did not differ between groups in either cohort. CYP3A4-metabolized statins slightly inhibit the antiplatelet activity of clopidogrel during dual antiplatelet therapy. However, they do not inhibit clopidogrel's antiplatelet effect in patients with high platelet reactivity or increase clinical events in patients following PCI.



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Suitability of functional evaluation embedded in serious game rehabilitation exercises to assess motor development across lifespan

Publication date: September 2017
Source:Gait & Posture, Volume 57
Author(s): B. Bonnechère, V. Sholukha, L. Omelina, M. Van Vooren, B. Jansen, S. Van Sint Jan
The aim of this study was to determine if the results of activities performed using specially developed serious games for physical rehabilitation could be used as an indicator of the natural maturation and decline of motor control in healthy participants. Eighty-one participants (19 children (5–15 years old), 40 adults (18–65 years old) and 22 aged subjects (60–88 years old) participated in this study. Motions performed were recorded using the Kinect sensor. Three different exercises embedded in the games were used to assess upper limb, trunk and lower limb control. The trial duration and accuracy, measures of gross motor function and fine motor control, respectively, were computed for each participant. ANOVA tests shows statistically significant differences between the three groups for duration (53±15, 27±10 and 119±30s for children, adults and elderly subjects respectively) and accuracy (87±5, 89±10 and 70±8% for children, adults and elderly subjects respectively). The slopes of the curves that approximated the evolution of the performance over various ages are coherent with previous studies about motor control development and physiological decline. The proposed solution, i.e. serious games rehabilitation exercises coupled to motion analysis, seems to be an interesting tool to assess global motor function. Further studies are needed to study the influence of pathologies on the studied parameters.



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newly available online.Revue de la Societe japono-francaise de Sociologie



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The new issue is now available.The St. Marianna Medical Journal

Vol.45 No.1

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The new issue is now available.Pediatric Otorhinolaryngology Japan

Vol.38 No.2

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The new issue is now available.Shikaigaku

Vol.71 No.3_4

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The new issue is now available.TRANSACTIONS OF THE JAPAN FLUID POWER SYSTEM SOCIETY

Vol.48 No.2

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The new issue is now available.Wind Engineers, JAWE

[No. 150]

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The new issue is now available.Shikaigaku

Vol.71 No.1

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The new issue is now available.Bulletin of Obihiro Otani Junior College

Vol.7

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The new issue is now available.Bulletin of Obihiro Otani Junior College

Vol.6

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The new issue is now available.Bulletin of Obihiro Otani Junior College

Vol.5

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The new issue is now available.Bulletin of Obihiro Otani Junior College

Vol.4

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The new issue is now available.Bulletin of Obihiro Otani Junior College

Vol.3

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The new issue is now available.Bulletin of Obihiro Otani Junior College

Vol.2

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The new issue is now available.Bulletin of Obihiro Otani Junior College

Vol.1

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The new issue is now available.Revue de la Societe japono-francaise de Sociologie

Vol.25

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The new issue is now available.Journal of Japan Society for Fuzzy Theory and Intelligent Informatics

Vol.16 No.1

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The new issue is now available.Journal of Japan Society for Fuzzy Theory and Intelligent Informatics

Vol.16 No.3

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The new issue is now available.Pediatric Otorhinolaryngology Japan

Vol.38 No.1

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newly available online.Japnese Journal of Educational Media Research



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The new issue is now available.Journal of Japan Society for Fuzzy Theory and Intelligent Informatics

Vol.15 No.5

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The death pathways in mussel larval cells after a freeze-thaw cycle

Publication date: Available online 28 May 2017
Source:Cryobiology
Author(s): Nelly A. Odintsova, Andrey V. Boroda, Mariia A. Maiorova, Konstantin V. Yakovlev
We analyzed cell viability, caspase activity, plasma membrane alterations and cell ultrastructure morphology to estimate the morphological and biochemical alterations that occur in bivalve molluscan cell cultures during cryopreservation. The use of 5% dymethyl sulfoxide as a cryoprotectant resulted in greater cell survival and a scarcity of destroyed cells lacking cytosol among dead cells. In this case, almost all cells died through necrosis or apoptosis, which appeared to increase in mussel cell cultures after a freeze-thaw cycle. Apoptosis was not a main death pathway in mussel cells, but it was induced in a significant part of these cells (up to 24%) immediately after thawing and depended mostly on the cryoprotectant used. Regardless of the type of the used cryoprotectant, we observed some nuclear aberrations in cells after freezing-thawing, such as few multipolar mitoses or the absence of a division spindle in mitotic cells. After analyzing different methods for assessing cell damage, the best results were obtained from optimal approaches that could provide information regarding the cell disruption level after freezing-thawing and could be considered for future studies.



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Physical Mechanical characterization of cosmetic formulations and correlation between instrumental measurements and sensorial properties

Abstract

Objective

The correct choice of raw materials in the development of cosmetic formulations is essential for obtaining stable and pleasant skin care products. Therefore, rheological, texture and sensory analyses are important to understand the behavior and stability of the formulations. In this context, the aim of the present study was to develop cosmetic formulations containing or not (vehicle) UV filters and chicory root extract, to evaluate their stability as well as to characterize their physical and texture properties and correlate them with the sensory attributes.

Methods

Four formulations containing organic UV filters and chicory extract, each alone or in combination, were developed and evaluated for 180 days with a cone and plate rheometer, a texture analyzer and consumer's sensorial analysis. Thus, the data obtained were correlated in order to observe the different influences.

Results

The developed formulations remained stable after 180 days regarding macroscopic aspects, organoleptic characteristics and pH values. The addition of the UV filters alone and in combination with the active substance resulted in significant increases in rheology, viscosity and consistency. The formulation with the active ingredient showed significant decreases in the texture parameters after 180 days, mainly due to its polysaccharide Inulin. All formulations obtained high scores in sensorial parameters. A strong correlation was mainly found between spreadability and work of shear, and between the texture parameters.

Conclusion

The raw materials strongly influenced the physical, texture and sensorial parameters. Finally, the UV filters showed a greater influence on the results of the formulations than the chicory root extract. In conclusion, the association of the mentioned methods allows the correct choice of ingredients and their combinations.

This article is protected by copyright. All rights reserved.



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Residents worry about 'irritating' odors emanating from oil and gas drilling site near Erie - The Denver Channel


The Denver Channel

Residents worry about 'irritating' odors emanating from oil and gas drilling site near Erie
The Denver Channel
“It makes my sinuses hurt,” she said, “and that day, it caused a burning in the back of my throat.” Fick, a veterinarian, said she worries about the volatile organic compounds (VOCs) being released into the air, that ... “Cancer risks estimates for ...

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Oral lichenoid dysplasia and exophytic oral verrucous hyperplasia: Mythical entities of oral pathology

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Publication date: Available online 27 May 2017
Source:Oral Oncology
Author(s): A. Thirumal Raj




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Editorial Board/Aims & Scope

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Publication date: June 2017
Source:Oral Oncology, Volume 69





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In Memoriam – Crispian Scully 1945–2017

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Publication date: June 2017
Source:Oral Oncology, Volume 69
Author(s): Jatin P. Shah




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The Combined Vaginoplasty Technique for Male-to-Female Sex Reassignment Surgery: Operative Approach and Outcomes

Publication date: Available online 27 May 2017
Source:Journal of Plastic, Reconstructive & Aesthetic Surgery
Author(s): Nikolaos A. Papadopulos, Dmitry Zavlin, Jean-Daniel Lellé, Peter Herschbach, Gerhard Henrich, Laszlo Kovacs, Benjamin Ehrenberger, Hans-Guenther Machens, Jürgen Schaff
BackgroundSeveral therapy options exist for male-to-female (MTF) transgenders desiring sex reassignment. Surgery includes numerous different procedures. Of those, vaginoplasty is predominant and aims at providing attractive aesthetics and fully functional genitals.The goal of this study was to present the surgical results of our modified combined vaginoplasty technique in a consecutive patient cohort.MethodsThe authors included 40 MTF transgender patients undergoing two-stage sex reassignment surgery (SRS) in an observational prospective study between September 2012 and January 2014. Demographic characteristics, medical and surgical history, operative details, and outcomes after surgery were documented. Postoperatively, 23 patients received a pelvic exam following standardized protocol.ResultsMeasured vaginal depth was 11.77 - 14.99 cm depending on dilator size used (25-40mm). Vaginal, clitoral, and labial sensitivity was intact and favorable in all examined patients. 19 women (47.5%) opted for breast augmentations to achieve feminine cosmesis making it the most common non-genital operation. Complications were mostly minor and temporary. Severe adverse events, such as wound infections (n = 3), colon injuries (3), short (1) or narrow (1) vaginas, or partial clitoral necroses (1), were rare and immediately addressed by the surgical team. No vaginal construction was lost and no secondary reconstructive approaches were required.ConclusionSatisfactory physical results and favorable low rates of complications endorse our combined technique for MTF SRS. These findings, however, need to be confirmed by other research groups as well. Therefore, in our opinion, MTF SRS remains an evolving area of development whose research is aiming to establish a state of the art surgical technique.



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If a butterfly flaps its wings in the Amazon, do we form an Inflammasome?

Publication date: June 2017
Source:Molecular Immunology, Volume 86
Author(s): Ashley Mansell




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Editorial Board/ Publication Information

Publication date: June 2017
Source:Molecular Immunology, Volume 86





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More patients presenting with HPV-associated oral cancers in Lubbock - LubbockOnline.com


More patients presenting with HPV-associated oral cancers in Lubbock
LubbockOnline.com
“In that same period, we have seen an increase in the HPV oropharyngeal cancer,” he said. “And oropharyngeal cancer — what it means it's affecting the base of your tongue and tonsils.” Dr. Brian Herring, a Lubbock dentist, chalks the increase up to ...



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More patients presenting with HPV-associated oral cancers in Lubbock - LubbockOnline.com


More patients presenting with HPV-associated oral cancers in Lubbock
LubbockOnline.com
“In that same period, we have seen an increase in the HPV oropharyngeal cancer,” he said. “And oropharyngeal cancer — what it means it's affecting the base of your tongue and tonsils.” Dr. Brian Herring, a Lubbock dentist, chalks the increase up to ...



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The effect of histone acetyl-transferase inhibitor trichostatin A on porcine mesenchymal stem cell transcriptome

Publication date: August 2017
Source:Biochimie, Volume 139
Author(s): Artur Gurgul, Jolanta Opiela, Klaudia Pawlina, Tomasz Szmatoła, Michał Bochenek, Monika Bugno-Poniewierska
The use of histone acetyl-transferase inhibitors such as trichostatin A (TSA) for epigenetic transformation of mesenchymal stem cells (MSCs), whose nuclei will be transferred into enucleated oocytes, is a novel approach in research involving somatic cell cloning of pigs and other mammalian species. Although the effectiveness of TSA in cloning applications was confirmed, processes and mechanisms underlying achieved effects are not yet fully understood, especially for pig MSCs. To contribute to this knowledge, in this study we performed a comprehensive transcriptome analysis using high-throughput sequencing of pig bone-marrow derived MSCs, both treated and untreated with TSA, and evaluated the effect of TSA administration on their transcription profile after 24 h of in vitro culture. The expression of selected positive and negative mesenchymal surface antigens was also evaluated in these cells by flow cytometry. Subsequently, the stability of induced expression changes was evaluated after another 55–72 h of culture without TSA. The results of this study showed that TSA does not affect the expression of the selected surface antigens related to MSC mesenchymal stemness origin, namely: CD90 (positive marker), CD31 and CD34 (negative markers) and has a wide stimulating effect on MSCs transcription, affecting genes across the whole genome with some minor signs of site-specific acting in regions on SSC2 and SSC6. TSA turned out to have a higher impact on already expressed genes with only minor abilities to induce expression of silenced genes. Genes with expression affected by TSA were related to a wide range of biological processes, however, we found some evidence for specific stimulation of genes associated with development, differentiation, neurogenesis or myogenesis. TSA also seemed to interfere with Wnt signaling pathways by upregulation of several engaged genes. The analysis of cell transcriptome after prolonged culture following the TSA removal, showed that the expression level of majority of genes affected by TSA is restored to the initial level. Nonetheless, the set of about six hundred genes responsible for e.g. adhesion, signal transduction and cell communication was altered even after 55–72 h of culture without TSA. TSA also enhanced expression of some of pluripotency marker genes (FGF2, LIF, TERT) but their expression was stabilized during further culture without TSA. The detailed analysis of factors connected with neuron-like differentiation allowed us to assume that TSA mostly stimulates neurogenic differentiation pathway in the pig MSCs possibly through interaction with Wnt-mediated signaling and thus triggers mechanisms conducive to epigenetic reprograming.



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TWiV 443: On a leaf, no one can hear you scream

The TWiVsters reveal the puppet master: an RNA virus injected with wasp eggs that paralyzes the ladybug so that she protects the cocoon until the adult emerges.

Hosts: Vincent Racaniello...



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Atypical non-verbal sensorimotor synchronization in adults who stutter may be modulated by auditory feedback

Publication date: Available online 27 May 2017
Source:Journal of Fluency Disorders
Author(s): Robert van de Vorst, Vincent L. Gracco
PurposeTo investigate if non-verbal sensorimotor synchronization abilities in adult individuals who stutter (IWS) differ from non-stuttering controls (NS) under various performance conditions (tempo, auditory feedback, use of hands [single/both] and rhythm).MethodsParticipants were 11 IWS (5 males, 6 females, Mean age=25.8, SD=8.7) and 11 age- and gender-matched controls (Mean age=24.4, SD=8.4). During the experiment, participants were asked to prepare three melodies and subsequently perform them with a metronome at different rates and auditory feedback modalities (non-altered and suppressed). For each task/condition we tracked timing asynchrony related to the steady metronome beat.Results and conclusions: Overall, IWS displayed significantly higher timing asynchrony. Of all conditions, auditory-feedback distinguished IWS from NS most strongly, a subgroup of IWS significantly benefitting from the absence of auditory feedback. In addition, IWS showed a non-significant trend of higher negative mean asynchrony (NMA) and were more affected by the slower rate and increased rhythmic complexity and occasionally suggested poorer beat perception. These results suggest aberrant timing of sensorimotor network interaction associated with the origin of developmental stuttering.



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SANITA' – Alla “Cattolica” di Campobasso la scena al Congresso di Radioterapia e oncologia di Vienna - Molise Network


Molise Network

SANITA' – Alla “Cattolica” di Campobasso la scena al Congresso di Radioterapia e oncologia di Vienna
Molise Network
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Utah Political Capitol

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Autofluorescence spectroscopy for nerve-sparing laser surgery of the head and neck—the influence of laser-tissue interaction

Abstract

The use of remote optical feedback systems represents a promising approach for minimally invasive, nerve-sparing laser surgery. Autofluorescence properties can be exploited for a fast, robust identification of nervous tissue. With regard to the crucial step towards clinical application, the impact of laser ablation on optical properties in the vicinity of structures of the head and neck has not been investigated up to now. We acquired 24,298 autofluorescence spectra from 135 tissue samples (nine ex vivo tissue types from 15 bisected pig heads) both before and after ER:YAG laser ablation. Sensitivities, specificities, and area under curve(AUC) values for each tissue pair as well as the confusion matrix were statistically calculated for pre-ablation and post-ablation autofluorescence spectra using principal component analysis (PCA), quadratic discriminant analysis (QDA), and receiver operating characteristics (ROC). The confusion matrix indicated a highly successful tissue discrimination rate before laser exposure, with an average classification error of 5.2%. The clinically relevant tissue pairs nerve/cancellous bone and nerve/salivary gland yielded an AUC of 100% each. After laser ablation, tissue discrimination was feasible with an average classification accuracy of 92.1% (average classification error 7.9%). The identification of nerve versus cancellous bone and salivary gland performed very well with an AUC of 100 and 99%, respectively. Nerve-sparing laser surgery in the area of the head and neck by means of an autofluorescence-based feedback system is feasible even after ER-YAG laser-tissue interactions. These results represent a crucial step for the development of a clinically applicable feedback tool for laser surgery interventions in the oral and maxillofacial region.



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Mesenchymal stromal cell and osteoblast responses to oxidized titanium surfaces pre-treated with λ  = 808 nm GaAlAs diode laser or chlorhexidine: in vitro study

Abstract

Preservation of implant biocompatibility following peri-implantitis treatments is a crucial issue in odontostomatological practice, being closely linked to implant re-osseointegration. Our aim was to assess the responses of osteoblast-like Saos2 cells and adult human bone marrow-mesenchymal stromal cells (MSCs) to oxidized titanium surfaces (TiUnite®, TiU) pre-treated with a 808 ± 10 nm GaAlAs diode laser operating in non-contact mode, in continuous (2 W, 400 J/cm2; CW) or pulsed (20 kHz, 7 μs, 0.44 W, 88 J/cm2; PW) wave, previously demonstrated to have a strong bactericidal effect and proposed as optional treatment for peri-implantitis. The biocompatibility of TiU surfaces pre-treated with chlorhexidine digluconate (CHX) was also evaluated. In particular, in order to mimic the in vivo approach, TiU surfaces were pre-treated with CHX (0.2%, 5 min); CHX and rinse; and CHX, rinse and air drying. In some experiments, the cells were cultured on untreated TiU before being exposed to CHX. Cell viability (MTS assay), proliferation (EdU incorporation assay; Ki67 confocal immunofluorescence analysis), adhesion (morphological analysis of actin cytoskeleton organization), and osteogenic differentiation (osteopontin confocal immunofluorescence analysis; mineralized bone-like nodule formation) analyses were performed. CHX resulted cytotoxic in all experimental conditions. Diode laser irradiation preserved TiU surface biocompatibility. Notably, laser treatment appeared even to improve the known osteoconductive properties of TiU surfaces. Within the limitations of an in vitro experimentation, this study contributes to provide additional experimental basis to support the potential use of 808 ± 10 nm GaAlAs diode laser at the indicated irradiation setting, in the treatment of peri-implantitis and to discourage the use of CHX.



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Supine posture affects cortical plasticity in elderly but not young women during a word learning-recognition task

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Publication date: Available online 27 May 2017
Source:Biological Psychology
Author(s): Chiara Spironelli, Alessandro Angrilli
The present research investigated the hypothesis that elderly and horizontal body position contribute to impair learning capacity. To this aim, 30 young (mean age: 23.2 years) and 20 elderly women (mean age: 82.8 years) were split in two equal groups, one assigned to the Seated Position (SP), and the other to the horizontal Bed Rest position (hBR). In the Learning Phase, participants were shown 60 words randomly distributed, and in the subsequent Recognition Phase they had to recognize them mixed with a sample of 60 new words. Behavioral analyses showed age-group effects, with young women exhibiting faster response times and higher accuracy rates than elderly women, but no interaction of body position with age group was found. Analysis of the RP component (250–270ms) revealed greater negativity in the left Occipital gyrus/Cuneus of both sitting age-groups, but significantly left-lateralized RP in left Lingual gyrus only in young bedridden women. Elderly hBR women showed a lack of left RP lateralization, the main generator being located in the right Cuneus. Young participants had the typical old/new effect (450–800ms) in different portions of left Frontal gyri/Uncus, whereas elderly women showed no differences in stimulus processing and its location. EEG alpha activity analyzed during a 3min resting state, soon after the recognition task, revealed greater alpha amplitude (i.e., cortical inhibition) in posterior sites of hBR elderly women, a result in line with their inhibited posterior RP. In elderly women the left asymmetry of RP was positively correlated with both greater accuracy and faster responses, thus pointing to a dysfunctional role, rather than a compensatory shift, of the observed right RP asymmetry in this group. This finding may have important clinical implications, with particular regard to the long-term side-effects of forced Bed Rest on elderly patients.



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Working hard for oneself or others: Effects of oxytocin on reward motivation in social anxiety disorder

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Publication date: Available online 27 May 2017
Source:Biological Psychology
Author(s): Angela Fang, Michael T. Treadway, Stefan G. Hofmann
There is some evidence to suggest that oxytocin promotes social behavior, especially for disorders characterized by social dysfunction, such as social anxiety disorder (SAD). The goal of this study was to examine the effect of oxytocin on reward motivation in SAD. We tested whether oxytocin promotes prosocial, or antisocial, self-directed decisions, and whether its effects depended on social anxiety severity and attachment. Fifty-two males with SAD received 24 international units of oxytocin or placebo, and completed a reward motivation task that measured willingness to work for self vs. other monetary rewards. Although there was no main drug effect, social anxiety severity moderated the effect of oxytocin. Less socially anxious individuals who received oxytocin worked harder for other vs. own rewards, compared to high socially anxious individuals. Attachment did not moderate this effect. Among people with SAD, oxytocin enhances prosocial behaviors in individuals with relatively lower levels of social anxiety.National Institutes of Health ClinicalTrials.gov Registry #NCT01856530.http://ift.tt/2s3Izlu.



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Behavioral and electrophysiological correlates of cognitive control in ex-obese adults

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Publication date: Available online 27 May 2017
Source:Biological Psychology
Author(s): Vincenza Tarantino, Vincenzo Vindigni, Franco Bassetto, Chiara Pavan, Antonino Vallesi
Impaired cognitive control functions have been documented in obesity. It remains unclear whether these functions normalize after weight reduction. We compared ex-obese individuals, who successfully underwent substantial weight loss after bariatric surgery, to normal weight participants on measures of resistance to interference, cognitive flexibility and response inhibition, obtained from the completion of two Stroop tasks, a Switching task and a Go/NoGo task, respectively. To elucidate the underlying brain mechanisms, event-related potentials (ERPs) in the latter two tasks were examined. As compared to controls, patients were more susceptible to the predominant but task-irrelevant stimulus dimension (i.e., they showed a larger verbal Stroop effect), and were slower in responding on trials requiring a task-set change rather than a task-set repetition (i.e., they showed a larger switch cost). The ERP correlates revealed altered anticipatory control mechanisms (switch positivity) and an exaggerated conflict monitoring response (N2). The results suggest that cognitive control is critical even in ex-obese individuals and should be monitored to promote weight loss maintenance.



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The Effect of Drying Parameters on the Quality of Pork and Poultry-Pork Kabanosy Produced according to the Traditional Specialties Guaranteed Recipe

The aim of this study was to determine the effect of differentiated air relative humidity during the drying process on selected quality features of TSG (traditional specialties guaranteed) pork and poultry-pork kabanosy. After heat treatment and 24-hour cooling at 4–6°C, the products were placed in three chambers at 15°C with differentiated air relative humidity: 60, 70, and 80%, respectively. The drying process was carried out until all variants of kabanosy achieved the required final yield of the product (

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Recent advancements in liposomes targeting strategies to cross blood-brain barrier (BBB) for the treatment of Alzheimer's disease

Publication date: 28 August 2017
Source:Journal of Controlled Release, Volume 260
Author(s): Mukta Agrawal, Ajazuddin, Dulal K. Tripathi, Swarnlata Saraf, Shailendra Saraf, Sophia G. Antimisiaris, Spyridon Mourtas, Margareta Hammarlund-Udenaes, Amit Alexander
In this modern era, with the help of various advanced technologies, medical science has overcome most of the health-related issues successfully. Though, some diseases still remain unresolved due to various physiological barriers. One such condition is Alzheimer; a neurodegenerative disorder characterized by progressive memory impairment, behavioral abnormalities, mood swing and disturbed routine activities of the person suffering from. It is well known to all that the brain is entirely covered by a protective layer commonly known as blood brain barrier (BBB) which is responsible to maintain the homeostasis of brain by restricting the entry of toxic substances, drug molecules, various proteins and peptides, small hydrophilic molecules, large lipophilic substances and so many other peripheral components to protect the brain from any harmful stimuli. This functionally essential structure creates a major hurdle for delivery of any drug into the brain. Still, there are some provisions on BBB which facilitate the entry of useful substances in the brain via specific mechanisms like passive diffusion, receptor-mediated transcytosis, carrier-mediated transcytosis etc. Another important factor for drug transport is the selection of a suitable drug delivery systems like, liposome, which is a novel drug carrier system offering a potential approach to resolving this problem. Its unique phospholipid bilayer structure (similar to physiological membrane) had made it more compatible with the lipoidal layer of BBB and helps the drug to enter the brain. The present review work focused on various surface modifications with functional ligand (like lactoferrin, transferrin etc.) and carrier molecules (such as glutathione, glucose etc.) on the liposomal structure to enhance its brain targeting ability towards the successful treatment of Alzheimer disease.

Graphical abstract

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PEG-PCL-based nanomedicines: A biodegradable drug delivery system and its application

Publication date: 28 August 2017
Source:Journal of Controlled Release, Volume 260
Author(s): Philip Grossen, Dominik Witzigmann, Sandro Sieber, Jörg Huwyler
The lack of efficient therapeutic options for many severe disorders including cancer spurs demand for improved drug delivery technologies. Nanoscale drug delivery systems based on poly(ethylene glycol)-poly(ε-caprolactone) copolymers (PEG-PCL) represent a strategy to implement therapies with enhanced drug accumulation at the site of action and decreased off-target effects. In this review, we discuss state-of-the-art nanomedicines based on PEG-PCL that have been investigated in a preclinical setting. We summarize the various synthesis routes and different preparation methods used for the production of PEG-PCL nanoparticles. Additionally, we review physico-chemical properties including biodegradability, biocompatibility, and drug loading. Finally, we highlight recent therapeutic applications investigated in vitro and in vivo using advanced systems such as triggered release, multi-component therapies, theranostics, or gene delivery systems.

Graphical abstract

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Nutrition in the Post-surgical Patient: Myths and Misconceptions

Abstract

Purpose of Review

Despite the large body of evidence supporting adequate early enteral nutrition (EN) in surgical patients, iatrogenic underfeeding is common. Myths and misconceptions persist and patients may receive suboptimal nutritional therapy as a result of outdated or uninformed practices. EN is safe and potentially beneficial in patients requiring vasopressor support. Early feeding proximal to a "fresh" anastomosis is safe.

Recent Findings

Routine monitoring of gastric residual volume (GRV) for tube feeding intolerance is no longer recommended, and routine post-pyloric feeding in patients without evidence of impaired gastric emptying does not lower the risk of aspiration. Awaiting the return of flatus before initiating post-operative feeding is not required. Albumin is not an accurate marker of nutritional adequacy in the hospital setting. Permissive underfeeding may not be beneficial for malnourished surgical patients.

Summary

This article addresses myths and misconceptions of enteral nutrition in surgical patients.



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Why are most phospholipidosis inducers also hERG blockers?

Abstract

Recent reports have noted that a number of compounds that block the human Ether-à-go-go related gene (hERG) ion channel also induce phospholipidosis (PLD). To explore a hypothesis explaining why most PLD inducers are also hERG inhibitors, a modeling approach was undertaken with data sets comprised of 4096 compounds assayed for hERG inhibition and 5490 compounds assayed for PLD induction. To eliminate the chemical domain effect, a filtered data set of 567 compounds tested in quantitative high-throughput screening (qHTS) format for both hERG inhibition and PLD induction was constructed. Partial least squares (PLS) modeling followed by 3D-SDAR mapping of the most frequently occurring bins and projection on to the chemical structure suggested that both adverse effects are driven by similar structural features, namely two aromatic rings and an amino group forming a three-center toxicophore. Non-parametric U-tests performed on the original 3D-SDAR bins indicated that the distance between the two aromatic rings is the main factor determining the differences in activity; at distances of up to about 5.5 Å, a phospholipidotic compound would also inhibit hERG, while at longer distances, a sharp reduction of the PLD-inducing potential leaves only a well-pronounced hERG blocking effect. The hERG activity itself diminishes after the distance between the centroids of the two aromatic rings exceeds 12.5 Å. Further comparison of the two toxicophores revealed that the almost identical aromatic rings to amino group distances play no significant role in distinguishing between PLD and hERG activity. The hypothesis that the PLD toxicophore appears to be a subset of the hERG toxicophore explains why about 80% of all phospholipidotic chemicals (the remaining 20% are thought to act via a different mechanism) also inhibit the hERG ion channel. These models were further validated in large-scale qHTS assays testing 1085 chemicals for their PLD-inducing potential and 1570 compounds for hERG inhibition. After removal of the modeling and experimental inconclusive compounds, the area under the receiver-operating characteristic (ROC) curve was 0.92 for the PLD model and 0.87 for the hERG model. Due to the exceptional ability of these models to recognize safe compounds (negative predictive values of 0.99 for PLD and 0.94 for hERG were achieved), their use in regulatory settings might be particularly useful.



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On the mechanisms of melatonin in protection of aluminum phosphide cardiotoxicity

Abstract

Aluminum phosphide (AlP), one of the most commonly used pesticides worldwide, has been the leading cause of self-poisoning mortalities among many Asian countries. The heart is the main organ affected in AlP poisoning. Melatonin has been previously shown to be beneficial in reversing toxic changes in the heart. The present study reveals evidence on the probable protective effects of melatonin on AlP-induced cardiotoxicity in rats. The study groups included a control (almond oil only), ethanol 5% (solvent), sole melatonin (50 mg/kg), AlP (16.7 mg/kg), and 4 AlP + melatonin groups which received 20, 30, 40 and 50 mg/kg of melatonin by intraperitoneal injections following AlP treatment. An electronic cardiovascular monitoring device was used to record the electrocardiographic (ECG) parameters. Heart tissues were studied in terms of oxidative stress biomarkers, mitochondrial complexes activities, ADP/ATP ratio and apoptosis. Abnormal ECG records as well as declined heart rate and blood pressure were found to be related to AlP administration. Based on the results, melatonin was highly effective in controlling AlP-induced changes in the study groups. Significant improvements were observed in the activities of mitochondrial complexes, oxidative stress biomarkers, the activities of caspases 3 and 9, and ADP/ATP ratio following treatment with melatonin at doses of 40 and 50 mg/kg. Our results indicate that melatonin can counteract the AlP-induced oxidative damage in the heart. This is mainly done by maintaining the normal balance of intracellular ATP as well as the prevention of oxidative damage. Further research is warranted to evaluate the possibility of using melatonin as an antidote in AlP poisoning.



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Molecular Characterization of Salmonella from Human and Animal Origins in Uganda

Sporadic Salmonella outbreaks with varying clinical presentations have been on the rise in various parts of Uganda. The sources of outbreaks and factors underlying the different clinical manifestation are curtailed by paucity of information on Salmonella genotypes and the associated virulence genes. This study reports molecular diversity of Salmonella enterica and their genetic virulence profiles among human and animal isolates. Characterization was done using Kauffman-White classification scheme and virulence genes analysis using multiplex PCR. Overall, 52% of the isolates belonged to serogroup D, 16% to serogroup E, 15% to poly F, H-S, and 12% to serogroup B. Serogroups A, C1, and C2 each consisted of only one isolate representing 5%. Virulence genes located on SPI-1 [spaN and sipB] and on SPI-2 [spiA] in addition to pagC and msgA were equally distributed in isolates obtained from all sources. Plasmid encoded virulence gene spvB was found in

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Biophysical Mechanisms Mediating Fibrin Fiber Lysis

The formation and dissolution of blood clots is both a biochemical and a biomechanical process. While much of the chemistry has been worked out for both processes, the influence of biophysical properties is less well understood. This review considers the impact of several structural and mechanical parameters on lytic rates of fibrin fibers. The influences of fiber and network architecture, fiber strain, FXIIIa cross-linking, and particle transport phenomena will be assessed. The importance of the mechanical aspects of fibrinolysis is emphasized, and future research avenues are discussed.

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Global Analysis of a Novel Nonlinear Stochastic SIVS Epidemic System with Vaccination Control

This paper proposes a stochastic SIVS epidemic system with nonlinear saturated infection rate under vaccination and investigates the dynamics predicted by the model. By using Itô’s formula and Lyapunov methods, we first study the existence and uniqueness of global positive solution. Then we investigate the stochastic dynamics of the system and obtain the thresholds which govern the extinction and the spread of the epidemic disease. Results show that large stochastic noises can lead to the extinction of epidemic diseases; that is, stochastic disturbances can suppress the outbreak of epidemic diseases. Finally, we carry out a series of numerical simulations to demonstrate the performance of our theoretical findings.

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AAA Rupture and Psoas Hematoma due to Type II Endoleak from Inferior Mesenteric Artery “Unusual” Collaterals

Although endovascular aneurysm repair (EVAR) in the abdominal aorta has reduced the perioperative mortality when compared with open repair, the need for reintervention after complications such as endoleak may be presented in up to 20% of the cases. Type II endoleak from branch vessels is often benign but can potentially be associated with progressive abdominal aortic aneurysm growth and sac expansion. We present a rare case of a patient who presented with sac expansion and psoas hematoma due to Type II endoleak from “unusual” collaterals of IMA and was treated successfully with endoleak microembolization and percutaneous decompression of the hematoma.

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Joint Power Allocation and Beamforming in Amplify-and-Forward Relay Networks under Per-Node Power Constraint

Two-way relay networks (TWRN) have been intensively investigated over the past decade due to their ability to enhance the performance assessment of networks in terms of cellular coverage and spectral efficiency. Yet, power control in such systems is a nontrivial issue, particularly in multirelay networks where relays are deployed to ensure a required Quality of Service (QoS). In this paper, we envision to address this critical issue by minimizing the sum-power with respect to per-node power consumption and acceptable users’ rates. To tackle this, we employ a variable transformation to turn the fractional quadratically constrained quadratic problem (QCQP) into semidefinite programming (SDP). This algorithm is also extended to a distributed format. Simulation results of deploying 10 relay stations reveal that the total power consumption will decrease to approximately 8 dBW for 6 bps/Hz sum-rate.

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Health and Safety Considerations of Fermented Sausages

Fermented sausages are highly treasured traditional foods. A large number of distinct sausages with different properties are produced using widely different recipes and manufacturing processes. Over the last years, eating fermented sausages has been associated with potential health hazards due to their high contents of saturated fats, high NaCl content, presence of nitrite and its degradation products such as nitrosamines, and use of smoking which can lead to formation of toxic compounds such as polycyclic aromatic hydrocarbons. Here we review the recent literature regarding possible health effects of the ingredients used in fermented sausages. We also go through attempts to improve the sausages by lowering the content of saturated fats by replacing them with unsaturated fats, reducing the NaCl concentration by partly replacing it with KCl, and the use of selected starter cultures with desirable properties. In addition, we review the food pathogenic microorganisms relevant for fermented sausages (Escherichia coli, Salmonella enterica, Staphylococcus aureus, Listeria monocytogenes, Clostridium botulinum, and Toxoplasma gondii) and processing and postprocessing strategies to inhibit their growth and reduce their presence in the products.

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Influence of Deformation and Stress between Bone and Implant from Various Bite Forces by Numerical Simulation Analysis

Endosseous oral implant is applied for orthodontic anchorage in subjects with multiple tooth agenesis. Its effectiveness under orthodontic loading has been demonstrated clinically and experimentally. This study investigates the deformation and stress on the bone and implant for different bite forces by three-dimensional (3D) finite element (FE) methods. A numerical simulation of deformation and stress distributions around implants was used to estimate the survival life for implants. The model was applied to determine the pattern and distribution of deformations and stresses within the endosseous implant and on supporting tissues when the endosseous implant is used for orthodontic anchorage. A threaded implant was placed in an edentulous segment of a human mandible with cortical and cancellous bone. Analytical results demonstrate that maximum stresses were always located around the implant neck in marginal bone. The results also reveal that the stress for oblique force has the maximum value followed by the horizontal force; the vertical force causes the stress to have the minimum value between implant and bone. Thus, this area should be preserved clinically to maintain the structure and function of a bone implant.

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A Study of Patients with Primary Mediastinal Germ Cell Tumors Treated Using Multimodal Therapy

Objectives. Primary mediastinal germ cell tumors (PMGCTs) are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. Methods. We examined 6 patients (median age: 25 years, range: 19–27 years) with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32.5 months (range: 8–84 months). Results. Three of the 6 patients received initial operation followed by 3-4 courses of chemotherapy (bleomycin, etoposide, and cisplatin (BEP) or etoposide and cisplatin (EP)). One patient developed multiple lung metastases 17 months after surgery; received salvage chemotherapy with vinblastine, ifosfamide, and cisplatin; and achieved complete remission. The remaining 3 patients received initial BEP and EP chemotherapy. Multiple lung metastases and supraclavicular lymph node metastases were detected in 2 of these patients at the initial diagnosis. The patients underwent resections to remove residual tumor after treatment, and no viable tumor cells were found. Conclusions. Reliable diagnosis and immediate multimodal treatments are necessary for patients with PMGCTs. The 6 patients treated in our hospital have never experienced recurrence after the multimodal treatment.

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