Pharmacogenetic analysis of irreversible severe cisplatin-induced nephropathy: a case report of a 27-year-old woman

In this report we describe a young patient diagnosed with bulky FIGO stage IIIb squamous cell cervix carcinoma with severe and irreversible nephropathy after three weekly low-doses of cisplatin. Besides several known risk factors such as hypomagnesemia and hypoalbuminemia, the patient also proved to be homozygously polymorphic for two polymorphisms within the COMT gene (c.615 + 310C>T and c.616–367C>T). As COMT polymorphism has been associated with cisplatin-induced ototoxicity, its effect on nephrotoxicity of cisplatin should be the subject of further investigation.

http://ift.tt/2rmT85k

Two-way DF relaying assisted D2D communication: ergodic rate and power allocation

In this paper, we investigate the ergodic rate for a device-to-device (D2D) communication system aided by a two-way decode-and-forward (DF) relay node. We first derive closed-form expressions for the ergodic r...

http://ift.tt/2qEMqUh

Combination of paclitaxel, bevacizumab and MEK162 in second line treatment in platinum-relapsing patient derived ovarian cancer xenografts

Abstract

Advanced ovarian cancer is very responsive to first line platinum therapy, however almost invariably it relapses with a resistant disease. We have reported that patient derived ovarian xenografts (PDXs), independently from the degree of the initial response to cisplatin (DDP), show a significantly lower response to a second DDP cycle. We here report the effect of new combination regimens containing a MEK inhibitor (MEK), bevacizumab (BEV) and paclitaxel (PTX) as second line therapy in platinum-relapsing PDXs.

We selected three DDP-relapsing PDX models based on the presence of activation of the RAS/RAF/MEK/ERK axis, mutated p53, lack of PTEN expression and activation of the PI3K pathway. In all the selected xenograft models, the antitumor efficacy of the doublets can be summarized as PTX/BEV > BEV/MEK > PTX/MEK and the antitumor activity of the triple combination was higher than any double combination. All the different combinations were well tolerated. The present data corroborate the activity of bevacizumab in combination with chemotherapy for the treatment of relapsing ovarian tumors and suggest that the addition of another targeted agents (MEK inhibitor) can further increase the antitumor activity without any increase in toxicity. PDX models represent a useful model to test second line therapy after failure of DDP first line.

http://ift.tt/2rDgZys

Randomised trial of mitral valve repair with leaflet resection versus leaflet preservation on functional mitral stenosis (The CAMRA CardioLink-2 Trial)

Background

The gold-standard treatment of severe mitral regurgitation (MR) due to degenerative disease is valve repair, which is surgically performed with either a leaflet resection or leaflet preservation approach. Recent data suggest that functional mitral stenosis (MS) may occur following valve repair using a leaflet resection strategy, which adversely affects patient prognosis. A randomised comparison of these two approaches to mitral repair on functional MS has not been conducted.

Methods and analysis

This is a prospective, multicentre randomised controlled trial designed to test the hypothesis that leaflet preservation leads to better preservation of mitral valve geometry, and therefore, will be superior to leaflet resection for the primary outcome of functional MS as assessed by 12-month mean mitral valve gradient at peak exercise. Eighty-eight patients with posterior leaflet prolapse will be randomised intraoperatively once deemed by the operating surgeon to feasibly undergo mitral repair using either a leaflet resection or leaflet preservation approach. Secondary end points include comparison of repair strategies with regard to mitral valve orifice area, leaflet coaptation height, 6 min walk test and a composite major adverse event end point consisting of recurrent MR ≥2+, death or hospital readmission for congestive heart failure within 12 months of surgery.

Ethics and dissemination

Institutional ethics approval has been obtained from all enrolling sites. Overall, there remains clinical equipoise regarding the mitral valve repair strategy that is associated with the least likelihood of functional MS. This trial hopes to introduce high-quality evidence to help surgical decision making in this context.

Trial registration number

NCT02552771.

http://ift.tt/2rmLLdT

Importance and added value of functional impairment to predict mortality: a cohort study in Swedish medical inpatients

Background

Accurate estimation of prognosis in multimorbid hospital patients could improve quality of care. This study aims to determine the relative importance and added value of a performance-based activities of daily living (ADL) measure with regard to mortality prediction.

Methods

200 inpatients, aged over 60 years, were recruited at the Department of General Internal Medicine at a tertiary university hospital. Two nested survival models were built, one with established risk factors (age, sex, Charlson comorbidity index, haemoglobin, albumin, body mass index and glomerular filtration rate), and one using the same covariates with the Gottfries-Bråne-Steen (GBS)-ADL measure added. The relative importance of GBS-ADL was evaluated in the full model. The added value of GBS-ADL was determined by comparing the nested models using four approaches: difference in overall ², discrimination, continuous net reclassification index (NRI >0) and integrated discrimination improvement (IDI).

Results

In the full model, GBS-ADL was the single most important predictor of mortality (²-df=30, p<0.001). The likelihood ratio ² test showed significant added value of ADL (p<0.001). The C-statistic was 0.78 with ADL and 0.72 without (difference 0.058, 95% CI 0.022 to 0.094). The NRI >0 was 0.42 (95% CI 0.20 to 0.58) and IDI 0.15 (95% CI 0.07 to 0.22).

Conclusions

Compared with a set of available clinical risk factors, impairment in ADL was a stronger predictor of all-cause mortality, showing substantial added value. Implementing quantitative ADL measurements could enable more appropriate and individual care for the elderly.

http://ift.tt/2skqXRy

Effectiveness of {alpha}2agonists for sedation in paediatric critical care: study protocol for a retrospective cohort observational study

Introduction

Mechanically ventilated children in paediatric intensive care units are commonly administered analgesics and sedative agents to minimise pain and distress and facilitate cooperation with medical interventions. Opioids and benzodiazepines are the most common analgesic and sedative agents but have safety concerns. The α₂ agonists clonidine and dexmedetomidine are alternative sedatives in use despite neither having robust evidence to support their use. Studies evaluating effectiveness of α₂ agonists to date have not focused on sedation-based outcomes instead focusing on opioid-sparing properties and ventilation outcomes. The aim of this study is to evaluate if an opioid-based sedation regimen, with an α₂ agonist adjunct (clonidine or dexmedetomidine), produces a non-inferior proportion of time adequately sedated compared with a control group without an α₂ agonist adjunct, while conferring potential additional benefits such as reduced opioid administration and less exposure to potential additional agents such as benzodiazepines.

Methods and analysis

We will conduct a retrospective cohort study in two Irish paediatric intensive care units using clinical information on patient characteristics, sedation scores and drug use. Eligible children admitted between January 2014 and June 2016 who were mechanically ventilated and received an opioid infusion will be included. Patients will be categorised into two exposure categories (received an α₂ agonist or did not receive an α₂ agonist) and the time adequately sedated (measured using the COMFORT Behaviour Score) will be calculated using interpolation of nursing sedation scores at each recorded time point. At least 150 per group is planned for inclusion to ensure adequate study power. Propensity score matching will be used in analysis to account for potential confounding by indication.

Ethics and dissemination

The study has been approved by the ethics committees of both hospitals. Dissemination will occur via local, national and international presentations for academic and healthcare audiences as well as through peer reviewed publications.

http://ift.tt/2skzAvF

Randomised healthcare policy evaluation of organised primary human papillomavirus screening of women aged 56-60

Objective

The aim of this research is to implement and reliably evaluate primary human papillomavirus (HPV) screening in an established and routinely running organised, large-scale population-based screening programme.

Participants

Resident women in the Stockholm/Gotland region of Sweden, aged 56–60 years were randomised to either (1) screening with cervical cytology, with HPV test in triage of low-grade cytological abnormalities (old policy) or (2) screening with HPV testing, with cytology in triage of HPV positives (new policy).

Outcome

The primary evaluation was the detection rate of cervical intraepithelial neoplasia grade 2 or worse (CIN2+).

Results

During January 2012–May 2014, the organised screening programme sent 42 752 blinded invitations with a prebooked appointment time to the women in the target age group. 7325 women attended in the HPV policy arm and 7438 women attended in the cytology arm. In the new policy, the population HPV prevalence was 5.5%, using an accredited HPV test (Cobas 4800). HPV16 prevalence was 1.0% (73/7325) and HPV18 prevalence was 0.3% (22/7325). In the HPV policy arm, 78/405 (19%) HPV-positive women were also cytology positive. There were 19 cases of CIN2+ in histopathology, all among women who were both HPV positive and cytology positive. The positive predictive value for CIN2+ in this group was 33.3% (19/57). In the cytology policy, 153 women were cytology positive and there were 18 cases of CIN2+ in histopathology. Both the total number of cervical biopsies and the number of cervical biopsies with benign histopathology were much lower in thepositive predictive value policy (49 benign, 87 total vs 105 benign, 132 total).

Conclusion

Primary HPV screening had a similar detection rate for CIN2+ as cytology-based screening, already before follow-up of HPV-positive, cytology-negative women with new HPV test and referral of women with persistence.

Trial registration number

NCT01511328.

http://ift.tt/2skIzwC

Exploring an adapted Risk Behaviour Diagnosis Scale among Indigenous Australian women who had experiences of smoking during pregnancy: a cross-sectional survey in regional New South Wales, Australia

Objectives

Explore Aboriginal women's responses to an adapted Risk Behaviour Diagnosis (RBD) Scale about smoking in pregnancy.

Methods and design

An Aboriginal researcher interviewed women and completed a cross-sectional survey including 20 Likert scales.

Setting

Aboriginal Community Controlled Health Services, community groups and playgroups and Aboriginal Maternity Services in regional New South Wales, Australia.

Participants

Aboriginal women (n=20) who were pregnant or gave birth in the preceding 18 months; included if they had experiences of smoking or quitting during pregnancy.

Primary and secondary outcome measures

Primary outcomes: RBD constructs of perceived threat and perceived efficacy, dichotomised into high versus low. Women who had quit smoking, answered retrospectively. Secondary outcome measures: smoking status, intentions to quit smoking (danger control), protection responses (to babies/others) and fear control responses (denial/refutation). Scales were assessed for internal consistency. A chart plotted responses from low to high efficacy and low to high threat.

Results

RBD Scales had moderate-to-good consistency (0.67–0.89 Cronbach's alpha). Nine women had quit and 11 were smoking; 6 currently pregnant and 14 recently pregnant. Mean efficacy level 3.9 (SD=0.7); mean threat 4.3 (SD=0.7). On inspection, a scatter plot revealed a cluster of 12 women in the high efficacy-high threat quadrant—of these 11 had quit or had a high intention of quitting. Conversely, a group with low threat-low efficacy (5 women) were all smokers and had high fear control responses: of these, 4 had low protection responses. Pregnant women had a non-significant trend for higher threat and lower efficacy, than those previously pregnant.

Conclusion

Findings were consistent with a previously validated RBD Scale showing Aboriginal smokers with high efficacy-high threat had greater intentions to quit smoking. The RBD Scale could have diagnostic potential to tailor health messages. Longitudinal research required with a larger sample to explore associations with the RBD Scale and quitting.

http://ift.tt/2sksozy

Healthcare costs of asthma comorbidities: a systematic review protocol

Introduction

Asthma is associated with many comorbid conditions that have the potential to impact on its management, control and outcomes. These comorbid conditions have the potential to impact on healthcare expenditure. We plan to undertake a systematic review to synthesise the evidence on the healthcare costs associated with asthma comorbidity.

Methods and analysis

We will systematically search the following electronic databases between January 2000 and January 2017: National Health Service (NHS) Economic Evaluation Database, Google Scholar, Allied and Complementary Medicine Database (AMED), Global Health, PsychINFO, Medline, Embase, Institute for Scientific Information Web of Science and Cumulative Index to Nursing and Allied Health Literature. We will search the references in the identified studies for additional potential papers. Additional literature will be identified by contacting experts in the field and through searching of registers of ongoing studies. The review will include cost-effectiveness and economic modelling/evaluation studies and analytical observational epidemiology studies that have investigated the healthcare costs of asthma comorbidity. Two reviewers will independently screen studies and extract relevant data from included studies. Methodological quality of epidemiological studies will be assessed using the Effective Public Health Practice Project tool, while that of economic evaluation studies will be assessed using the Drummond checklist. This protocol has been published in International Prospective Register of Systematic Reviews (PROSPERO) database (No. CRD42016051005).

Ethics and dissemination

As there are no primary data collected, formal NHS ethical review is not necessary. The findings of this systematic review will be disseminated in a peer-reviewed journal and presented at relevant conferences.

PROSPEROregistration number

CRD42016051005.

http://ift.tt/2rmEMS9

Monthly News Roundup - May 2017

Actemra: First Drug Approved to Treat Giant Cell Arteritis Actemra (tocilizumab) from Hoffman La Roche has gained a new indication as the first drug approved to treat adults with giant cell arteritis, a specific type of vasculitis. Vasculitis is...

http://ift.tt/2qEET7P

The effect of preoperative oral administration of prednisolone on postoperative pain in patients with symptomatic irreversible pulpitis: a single centre randomized controlled trial

Abstract

Aim

This single-centre randomized, double-blind, placebo-controlled clinical trial assessed the effect of preoperative, single, oral dose of prednisolone on postoperative pain and postoperative analgesic intake in patients with symptomatic, irreversible pulpitis in mandibular molars.

Methodology

Four hundred participants, randomly assigned into two equal groups, received either 40mg prednisolone or placebo tablets 30min before single-visit root canal treatment. Patients recorded their pain level 6, 12 and 24h after treatment on a 100-mm visual analogue scale (VAS). All patients received a sham capsule to take if needed as a postoperative analgesic and, if the pain persisted, an analgesic was prescribed. The relative risk reduction and 95% confidence intervals (CI) were estimated for binary data. Mann-Whitney U-test was used to compare postoperative pain intensity between groups.

Results

The relative risk reduction of pain incidence was 20.31% (95% CI: 12.03%, 27.82%) at 6h, 23.39% (95% CI: 14.75%, 31.16%) at 12h and 28.85% (95% CI: 18.08%, 38.20%) at 24h. Prednisolone had significantly less post-obturtion pain intensity compared to placebo at 6, 12 and 24h (p<0.001). The relative risk reduction of sham-capsule intake was 54% (95% CI: 38%, 66%) and of analgesic intake was 55% (95% CI: 3%, 79%). No adverse effects were recorded.

Conclusion

Preoperative oral administration of a single dose of 40mg prednisolone was beneficial to control short-term post-obturation pain after single visit root canal treatment in patients with symptomatic irreversible pulpitis reducing pain incidence after 24h by approximately 30% and postoperative analgesic intake by approximately 55%.

This article is protected by copyright. All rights reserved.

http://ift.tt/2rmP8l3

Peripancreatic paraganglioma mimics pancreatic/gastrointestinal neuroendocrine tumor on fine needle aspiration: report of two cases and review of the literature

Abstract

Cytologic diagnosis of extra-adrenal paraganglioma presenting as a peripancreatic mass is challenging with a high error rate due to its rarity. We report two cases of peripancreatic masses identified by radiology. Endoscopic ultrasound-guided fine needle aspiration (FNA) of the masses showed a moderately cellular tumor composed of small to medium sized neoplastic cells with round to oval nuclei, arranged singly and in loose clusters. Focal rosette-like structures were present. The cells were positive for neuroendocrine markers (synaptophysin and chromogranin). A diagnosis of a neoplasm with neuroendocrine differentiation and neuroendocrine tumor was made respectively on FNA for each case. The subsequent surgical resection of the tumors revealed peripancreatic paraganglioma. Although paraganglioma has been reported in the literature, the detailed comparison of perpancreatic paraganglioma versus pancreatic/gastrointestinal neuroendocrine tumor is still lacking. Therefore using these two cases with literature review, we wish to illustrate the differential diagnosis between these two entities based on cytomorphology and immunohistochemical study.

http://ift.tt/2qEwNfv

Cytopathology of high-grade fetal adenocarcinoma of the lung: A case report and cytological analysis

http://ift.tt/2r9HEBA

Significance of flower pot cells in effusion cytology

Cells with long polar hair-like processes referred to as 'flower pot cells' are a rare but beautiful morphological feature observed in effusions of diverse etiologies. This report describes these cells in effusions seen in ovarian borderline serous tumours, malignant mesothelioma and in reactive mesothelial cells with or without accompanying malignant cells. These processes were better appreciated in air-dried May-Grunwald-Giemsa stained smears.

http://ift.tt/2qElHam

The impact of a multifaceted intervention including sepsis electronic alert system and sepsis response team on the outcomes of patients with sepsis and septic shock

Compliance with the clinical practice guidelines of sepsis management has been low. The objective of our study was to describe the results of implementing a multifaceted intervention including an electronic al...

http://ift.tt/2rCYtq2

Magnetic inductive phase shift: a new method to differentiate hemorrhagic stroke from ischemic stroke on rabbit

The major therapy for ischemic stroke is thrombolytic treatment, but severe consequences occur when this method is used to treat hemorrhagic stroke. Currently, computed tomography and magnetic resonance imagin...

http://ift.tt/2skyoYU

Test–retest reliability of mandibular morphology measurements on cone-beam computed tomography-synthesized cephalograms with random head positioning errors

Cephalometric radiography has been used for orthodontic and surgical treatment planning and assessment, and for quantifying mandibular growth. However, it remains unclear how head positioning errors and the le...

http://ift.tt/2rmhwUj

A photoacoustic imaging reconstruction method based on directional total variation with adaptive directivity

In photoacoustic tomography (PAT), total variation (TV) based iteration algorithm is reported to have a good performance in PAT image reconstruction. However, classical TV based algorithm fails to preserve the...

http://ift.tt/2skjm5F

The HGF/c-MET pathway is a driver and biomarker of VEGFR-inhibitor resistance and vascular remodeling in non-small cell lung cancer.

Purpose: Resistance to vascular endothelial growth factor receptor (VEGFR) inhibitors is a major obstacle in the treatment of non-small cell lung cancer (NSCLC). We investigated the cellular mechanisms mediating resistance of NSCLCs to VEGFR tyrosine kinase inhibitors.<br /><br />Experimental Design: We generated murine models of human NSCLC and performed targeted inhibition studies with the VEGFR TKIs cediranib and vandetanib. We used species-specific hybridization of microarrays to compare cancer (human) and stromal (mouse) cell transcriptomes of TKI-sensitive and -resistant tumors. We measured tumor microvascular density and vessel tortuosity to characterize the effects of therapy on the tumor vascular bed. Circulating cytokine and angiogenic factor levels in patients enrolled in VEGFR TKI trials were correlated with clinical outcomes.<br /><br />Results: Murine xenograft models of human lung adenocarcinoma were initially sensitive to VEGFR TKIs, but developed resistance to treatment. Species-specific microarray analysis identified increased expression of stromal-derived hepatocyte growth factor (HGF) as a candidate mediator of TKI resistance and its receptor, c-MET, was activated in cancer cells and tumor-associated stroma. A transient increase in hypoxia-regulated molecules in the initial response phase was followed by adaptive changes resulting in a more tortuous vasculature. Forced HGF expression in cancer cells reduced tumor sensitivity to VEGFR TKIs and produced tumors with tortuous blood vessels. Dual VEGFR/c-MET signaling inhibition delayed the onset of the resistant phenotype and prevented the vascular morphology alterations. In cancer patients receiving VEGFR TKIs, high pretreatment HGF plasma levels correlated with poorer survival. <br /><br />Conclusions: HGF/c-MET pathway mediates VEGFR inhibitor-resistance and vascular remodeling in NSCLC.

http://ift.tt/2skd7yv

Expression of Five Neuroblastoma Genes in Bone Marrow or Blood of Patients with Relapsed/Refractory Neuroblastoma Provides a New Biomarker for Disease and Prognosis

Purpose: We determined if quantifying neuroblastoma (NB)-associated mRNAs (NB-mRNA) in bone marrow (BM) and blood improves assessment of disease and prediction of disease progression in patients with relapsed/refractory NB. <br /><br />Patients and Methods: mRNA for CHGA, DCX, DDC, PHOX2B, and TH was quantified in BM and blood from 101 patients concurrently with clinical disease evaluations. Correlation between NB-mRNA (delta cycle threshold [Ct] for the geometric mean of genes from the TaqMan® Low Density Array NB5 assay) and morphologically-defined tumor cell percentage in BM, ¹²³I-meta-iodobenzylguanidine (MIBG) Curie score, and CT/MRI-defined tumor longest diameter was determined. Time-dependent covariate Cox regression was used to analyze the relationship between DCt and progression-free survival (PFS). <br /><br />Results: NB-mRNA was detectable in 83% of BM (185/223) and 63% (89/142) of blood specimens, and their DCts were correlated (Spearman r=0.67, p<0.0001) although BM Ct was 7.9±0.5 Ct stronger than blood Ct. When BM morphology, MIBG, or CT/MRI were positive, NB-mRNA was detected in 99% (99/100), 88% (100/113), and 81% (82/101) of BMs. When all three were negative, NB-mRNA was detected in 55% (11/20) of BMs. BM NB-mRNA correlated with BM morphology or MIBG positivity (p<0.0001 and p=0.007). BM and blood Cts correlated with PFS (p<0.001; p=0.001) even when BM was morphologically negative (p=0.001; p=0.014). Multivariate analysis showed that BM and blood Cts were associated with PFS independently of clinical disease and MYCN gene status (p<0.001; p=0.055). <br /><br />Conclusions: This five-gene NB5 assay for NB-mRNA improves definition of disease status and correlates independently with PFS in relapsed/refractory NB.

http://ift.tt/2rmkpVj

Giving birth: Expectations of first time mothers in Switzerland at the mid point of pregnancy

Publication date: Available online 30 May 2017
Source:Women and Birth
Author(s): Valerie Fleming, Yvonne Meyer, Franziska Frank, Susanne van Gogh, Laura Schirinzi, Bénédicte Michoud, Claire de Labrusse
Problem and backgroundDespite a generally affluent society, the caesarean section rate in Switzerland has steadily climbed in recent years from 22.9% in 1998 to 33.7% in 2014. Speculation by the media has prompted political questions as to the reasons. However, there is no clear evidence as to why the Swiss rate should be so high especially in comparison with neighbouring countries.AimTo describe the emerging expectations of giving birth of healthy primigravid women in the early second semester of pregnancy in four Swiss cantons.MethodsQualitative individual interviews with 58 healthy primigravid women, were audio recorded, transcribed and subjected to thematic analysis. Recruitment took place through public and private hospitals, birth centres, obstetricians and independent midwives. The main ethical issues were informed consent, autonomy, confidentiality and anonymity.FindingsThe three main themes identified were taking or avoiding decisions, experiencing a continuum of emotions and planning the care.DiscussionBeing pregnant was part of a project women had mapped out for their lives. Only three women in our sample expressed a wish for a caesarean section. One of the strongest emotions was that of fear but in contrast some participants expressed faith that their bodies would cope with the experience.ConclusionBringing together the three languages and cultures produced a truly "Swiss" study showing contrasts between a matter of fact approach to pregnancy and the concept of fear. Such a contrast is worthy of further and deeper exploration by a multi-disciplinary research team.



http://ift.tt/2rmolVX

Combining Carcinoembryonic Antigen and Platelet to Lymphocyte Ratio to Predict Brain Metastasis of Resected Lung Adenocarcinoma Patients

We aimed to evaluate the role of pretreatment carcinoembryonic antigen (CEA) and platelet to lymphocyte ratio (PLR) in predicting brain metastasis after radical surgery for lung adenocarcinoma patients. The records of 103 patients with completely resected lung adenocarcinoma between 2013 and 2014 were reviewed. Clinicopathologic characteristics of these patients were assessed in the Cox proportional hazards regression model. Brain metastasis occurred in 12 patients (11.6%). On univariate analysis, N2 stage (P = 0.013), stage III (P = 0.016), increased CEA level (P = 0.006), and higher PLR value (P = 0.020) before treatment were associated with an increased risk of developing brain metastasis. In multivariate model analysis, CEA above 5.2 ng/mL (P = 0.014) and PLR ≥ 120 (P = 0.036) remained as the risk factors for brain metastasis. The combination of CEA and PLR was superior to CEA or PLR alone in predicting brain metastasis according to the receiver operating characteristic (ROC) curve analysis (area under ROC curve, AUC 0.872 versus 0.784 versus 0.704). Pretreatment CEA and PLR are independent and significant risk factors for occurrence of brain metastasis in resected lung adenocarcinoma patients. Combining these two factors may improve the predictability of brain metastasis.

http://ift.tt/2qzr7nB

Promoting Mental Health in Italian Middle and High School: A Pilot Study

Aim. In Italy, a handbook has been developed based on the principles of cooperative learning, life skills, self-effectiveness, and problem-solving at high school level. Early studies have shown the handbook's effectiveness. It has been hypothesized that the revised handbook could be more effective in middle schools. Method. The study design is a "pre- and posttest" that compares the results obtained from 91 students of the high schools with those of the 38 students from middle schools. The assessment was made through "self-reporting" questionnaires of (a) learning skills including problem-solving and (b) perceived self-efficacy in managing emotions, dysfunctional beliefs, and unhealthy behaviours (i.e., drinking/smoking). Results. Significant improvements were observed in both groups with the exceptions of perceived self-efficacy in managing emotions. The improvement of dysfunctional beliefs and the learning of problem-solving skills were better in middle schools. Conclusion. The results confirm the authors' hypothesis that the use of this approach is much more promising in middle school.

http://ift.tt/2qzuV8h

Effect of the 2014 Clinical and Laboratory Standards Institute urine-specific breakpoints on cefazolin susceptibility rates at a community teaching hospital

Enterobacteriaceae, which include Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis, are identified as the infectious etiology in the majority of urinary tract infections (UTIs) in community hospital...

http://ift.tt/2scjKDW

In vitro quality evaluation of leading brands of ciprofloxacin tablets available in Bangladesh

Ciprofloxacin is a broad-spectrum antibiotic that acts against a number of bacterial infections. The study was carried out to examine the in vitro quality control tests for ten leading brands of ciprofloxacin ...

http://ift.tt/2rm2WMI

Quercetin attenuates, indomethacin-induced acute gastric ulcer in rats

Background: Peptic ulcer diseases are common and are induced by many factors, including stress, smoking, and ingestion of non-steroidal anti-inflammatory drugs. Quercetin is considered to be an anti-oxidant with healing effects on many experimental toxic injuries. The present study aimed to explore the possible effect of quercetin on acute gastric ulcer induced by indomethacin in rats.

Materials and methods: Three groups received indomethacin (30 mg/kg body weight) orally by orogastric gavage on two consecutive days. The rats received famotidine (50 mg/kg body weight), quercetin (50 mg/kg body weight), or vehicle alone for 15 consecutive days by oral gavage. The control group received no indomethacin but received vehicle for 15 days by oral gavage. The ulcer index, volume, and pH of gastric juice were measured, and the stomachs were examined by routine light microscopy.

Results: Compared with the control group, the indomethacin-treated rats showed a marked damage of the gastric mucosal surface and a high ulcer index. In the famotidine- and quercetin-treated groups, significantly increased antioxidant enzyme activities were observed. The congestion, erosions, and necrosis were reduced with mild inflammatory cell infiltration while no major damage of endothelial cells was observed in the treated rats.

Conclusions: The findings of the study show that quercetin had antioxidant effect and can protect gastric mucosa against indomethacin-induced gastric ulceration than famotidine.  

http://ift.tt/2rm7dzX

Findings May Lead to New Strategies for GVHD [News in Brief]

A study in mice suggests that activating the RIG-I and STING signaling pathways has a protective effect on the gut.

http://ift.tt/2qE1LEw

Anatomical study of the renal excretory system in pigs. A review of its characteristics as compared to its human counterpart

Background: Despite the importance of the pyelocalyceal system in the pig as an experimental model, there is little information about this particular anatomical subject. We determined the morphological characteristics of the renal excretory system in pigs.

Materials and methods: This descriptive cross-sectional study evaluated 130 pairs of kidneys of pigs destined to slaughter. The pyelocalyceal system was subjected to injection technique — corrosion by infusion of polyester resin (85% Palatal and 15% Styrene) and subsequent infusion in potassium hydroxide (KOH) for 10 days. The significance level used was p < 0.05.

Results: The renal excretory system is characterised by the presence of type A major cranial and caudal calyxes seen in 34.3% of the kidneys (type A1 in 30% and type A2 in 4.3%). type B calyxes, corresponding to minor calyxes draining directly into the renal pelvis, were present in 65.7% of the specimens (type B1 59.2%; type B2 6.5% of the cases). The number of minor calyxes in the collector system was 7.9 ± 2.27 with statistically significant differences in side (p = 0.0047).

Conclusions: The morphometric characteristics of the kidneys in this study are slightly smaller than reported in humans. Similarly, the incidence of type A renal excretory system distribution is highest in humans and lowest in pigs. Due to its few morphological differences, the pig kidney is an excellent model for teaching- -learning processes, for research purposes, and for training of urologic applications.  

http://ift.tt/2skiQ7I

Tetrafurcation of the subscapular artery. Anatomical and clinical implications

Anatomic variations of axillary artery branches are commonly encountered during radiological investigation and surgical operations. Their existence can confuse interpretation of radiological results and lead to undesired complications during surgery. In this report authors describe a rare case of a subscapular arterial trunk that gave origin to thoracodorsal, circumflex scapular, posterior humeral circumflex, and lateral thoracic artery. Such a variation might cause undesired sequelae during trauma management and a variety of common flap harvesting operations including latissimus dorsi, scapular and parascapular flaps. Furthermore it presents embryological interest as it gives insight to embryologic development of axillary area.

http://ift.tt/2rmjtQI

The variable origin of the lateral circumflex femoral artery: a meta-analysis and proposal for a new classification system

The lateral circumflex femoral artery (LCFA) is responsible for vascularisation of the head and neck of the femur, greater trochanter, vastus lateralis and the knee. The origin of the LCFA has been reported to vary significantly throughout the literature, with numerous branching patterns described and variable distances to the mid-inguinal point reported. The aim of this study was to determine the estimated population prevalence and pooled means of these anatomical characteristics, and review their associated clinical relevance. A search of the major electronic databases was performed to identify all articles reporting data on the origin of the lateral circumflex femoral artery and its distance to the mid-inguinal point. Additionally, an extensive search of the references of all relevant articles was performed. All data on origin, branching, and distance to mid-inguinal point was extracted and pooled into a meta-analysis. A total of 26 articles (n = 3731 lower limbs) were included in the meta-analysis. Lateral circumflex femoral artery most commonly originates from the deep femoral artery with a pooled prevalence of 76.1% (95% confidence interval 69.4–79.3). The deep femoral artery-derived lateral circumflex femoral artery was found to originate with a mean pooled distance of 51.06 mm (95% confidence interval 44.61–57.51 mm) from the mid-inguinal point. Subgroup analysis of both gender and limb side data were consistent with these findings. Due to variability in the lateral circumflex femoral artery's origin and distance to mid-inguinal point, anatomical knowledge is crucial for clinicians to avoid iatrogenic injuries when performing procedures in the femoral region, and thus radiographic assessment prior to surgery is recommended. Lastly, we propose a new classification system for origin of the lateral circumflex femoral artery

http://ift.tt/2ska5ul

An anatomical investigation of the carotid canal

Background: The carotid canal (CC) located in the petrous temporal bone transmits the internal carotid artery, internal carotid venous plexus and sympathetic nerve plexus from the neck into the cranial cavity. It is an accessible passage into the cranial cavity and is considered an important anatomical landmark for neurosurgeons. The aim of this study was to investigate the topographical, morphometric and morphological parameters of the CC.

Materials and methods: An examination of the CC and related adjacent structures in 81 dry skull specimens was performed. Distribution of sample by sex was 34 females and 47 males, and by race 77 African and 4 Caucasian. The mean age was 50 years (range: 14–100 years).

Results: The external opening of the CC was found to be round-shaped, oval-shaped and tear-drop-shaped in 28.4%, 49.4% and 22.2% of the specimens, respectively. (1) Mean diameters [mm]: (a) medio-lateral 7.52 mm and (b) antero-posterior 5.41mm. Statistically significant difference in the vertical diameter was recorded in the race groups and laterality of the samples. (2) Mean distances [mm] between: (a) medial margins of external opening of CC was 50.03 mm, (b) lateral margins of external opening of CC was 62.73 mm and (c) external openings of CC and foramen lacerum was 15.6 mm. There was a statistically significant correlation between race and location of the opening of external CC in relation to foramen lacerum (viz. postero-lateral, lateral and diagonal, and lateral).

Conclusions: The present study corroborated previous reports on the CC; however, the tear-drop shaped external CC opening was a unique finding. The knowledge of the reference measurements pertaining to the CC and its relationship to adjacent structures may postulate a suitable surgical "safe-zone" range within the CC area.

http://ift.tt/2rmhCeH

A plea for extension of the anatomical nomenclature. Part 1: Nervous system and senses

A correct, exact, concise and detailed anatomical nomenclature is a cornerstone of communication not only in anatomy and related subjects but also in other medical branches and in the whole medical education. Terminologia Anatomica fulfils this task but some important structures are still missing there. The authors have collected and present here a list of terms including their definitions or explanations to provoke discussion about possible extension of the Terminologia Anatomica. The first part of this contribution, presented in this article, comprises 113 terms concerning the regulation systems of the human body: endocrine glands, central and peripheral nervous system, and senses. It also contains some corrections of anatomical mistakes, systemic inconsistencies and grammar changes.

http://ift.tt/2skbzEP

Enthesopathic patterns of two South African female cadavers

Enthesopathy is considered to be an osseous phenomenon, either disease-specific or bone-site specific, which occurs at the enthesis of bone. Upon routine cadaveric dissection of the glenohumeral region in two Caucasian females, enthesopathy of the right proximal humerus was observed unilaterally in both cases. Case 1 exhibited an inconsistent pattern of bony protuberances and crests dispersed across the lesser and greater tuberosities of the right humeral head. Varying degrees of ossification of the distal subscapularis muscle was also observed. Case 2 presented with a distinctively large enthesophyte that protruded supero-medially from the proximal right humerus. In addition, ossification of the distal-most aspect of the supraspinatus muscle was identified. Cases 1 and 2 were both reflective of osteophytic enthesopathy as proliferative change was clearly visible on the proximal aspect of each humerus. Whilst the presence of enthesopathies may be indicative of underlying pathology, it may prove beneficial to the field of bioarchaeology for the remodelling of lifestyles of ancient civilizations through the provision of current day variations as seen in these two case studies.

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The relationship between the dimensions of the internal auditory canal and the anomalies of the vestibulocochlear nerve

Background: Internal auditory canal (IAC) stenosis and vestibulocochlear nerve (VCN) abnormalities have been reported to be associated with sensorineural hearing loss. Previous studies classified the normal dimensions of the IAC and its anomalies with no consideration of the VCN. Other studies categorised the VCN development in only stenotic canals. In the present study, an anatomical classification of the normal dimensions of the IAC and its anomalies and their association with malformations of the VCN and its subdivisions were described.

Materials and methods: Retrospective review was undertaken for children ranged from 1 to 10 years. A total of 764 canals were investigated for pre-operative assessment of cochlear implantation. Other 100 canals of normal hearing ears were included as the control group. The maximum anteroposterior diameter, considered the width of the canal, was measured in axial plane and the length of the canal was identified in coronal plane. The canals were categorised normal: if they are from 3 to 8 mm, patulous: if they are more than 8 mm, stenotic: if they are less than 3 mm and atretic if absent, using multislice computed tomography. The VCN trunks and their subdivisions were investigated using magnetic resonance imaging.

Results: Internal auditory canals were found normal in 66% with a mean width: 5.27 ± ± 0.68, patulous in 17% with a mean width 113% more than that of the control group (p = 0.000), stenotic in 13% with a mean width 73% less as compared to that of the control group (p = 0.000) and atretic in 4% of the experimental canals. The VCN trunks were found normal with well-developed subdivisions in 77.8% of the normal canals, 98.4% of the patulous canals, and 19.2% of the stenotic canals. The VCN trunks were normal with hypoplastic subdivisions in 11.3% of the normal canals, 1.6% in the patulous canals, and 61.6% in the stenotic canals with a mean width 52% less than that of the normal trunk with developed subdivisions. Hypoplastic VCN trunks with absent subdivisions were reported in 7.3% of the normal canals, 11.1% of the stenotic canals and in 3.2% of the atretic canals. The VCN trunks were not found in 3.6% of the normal canals, in 8.1% of the stenotic canals and in 96.8% of the atretic canals.

Conclusions: Internal auditory canal formation was dependent on the process of development and growth of the eighth cranial nerve and its subdivisions that greatly affected the completion of IAC canalisation. This paper could serve as a reference providing a quantitative classification of the relationship between the dimensions of the IAC and the development of the VCN trunk and its subdivisions.

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An arthroscopic evaluation of the anatomical “critical zone”

Background: The "critical zone", a region of speculated vascularity, is situated approximately 10 mm proximal to the insertion of the supraspinatus tendon. Despite its obvious role as an anatomical landmark demarcator, its patho-anatomic nature has been identified as the source of rotator cuff pathology. Although many studies have attempted to evaluate the vascularity of this region, the architecture regarding the exact length, width and shape of the critical zone, remains unreported. This study aimed to determine the shape and morphometry of the "critical zone" arthroscopically.

Materials and methods: The sample series, which was comprised of 38 cases (n = 38) specific to pathological types, employed an anatomical investigation of the critical zone during routine real-time arthroscopy. Demographic representation: i) sex: 19 males, 19 females; ii) age range: 18–76 years; iii) race: white (n = 29), Indian (n = 7) and coloured (n = 2).

Results: The incidence of shape and the mean lengths and widths of the critical zone were determined in accordance with the relevant demographic factors and patient history. Although the cresenteric shape was predominant, hemispheric and sail-shaped critical zones were also identified. The lengths and widths of the critical zone appeared markedly increased in male individuals. While the increase in age may account for the increased incidence of rotator cuff degeneration due to poor end-vascular supply, the additional factors of height and weight presented as major determinants of the increase in size of the critical zone.

Conclusions: In addition, the comparisons of length and width with each other and shape yielded levels of significant difference, therefore indicating a directly proportional relationship between the length and width of the critical zone. This detailed understanding of the critical zone may prove beneficial for the success of post-operative rotator cuff healing.

http://ift.tt/2rmdJ9V

Morphological characteristics of visual cells in the endemic Korean loach Kichulchoia multifasciata (Pisces; Cobitidae) by microscopy

The visual cell of the retina in the Korean loach Kichulchoia multifasciata, a bottom-dwelling freshwater loach in shallow water, contains double cones and large rods. With light microscopy, the cones form a row mosaic pattern in which the partners of double cones are linearly oriented with a large rod. In a double cone or twin cone, the two members are unequal such that one cone may be longer than the other. An anatomical unit is apparent which consists of 5 rod cells and 15 double cone cells per 20 × 20 μm area. We found that the cone cells of outer segments are linked to the inner segment by so-called "calyceal process" using a scanning electron microscopy, unlike rod cells. In the transmission electron microscopy, the outer membrane shows piles of membrane discs surrounded by double membranes.  

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What can anthropometric measurements tell us about obstructive sleep apnoea?

Background: Clinical detection of anatomic narrowing of the upper airway may facilitate early recognition of obstructive sleep apnoea (OSA). The aim of this study was to investigate whether anthropometric measurement can be used to predict OSA.

Materials and methods: One hundred forty-seven subject were included from those patients who were referred to our sleep laboratory with suspected sleep apnoea. All patients were divided two groups with respect to the apnoea-hypopnoea index (AHI). The first group was diagnosed as OSA, AHI greater than 5. The second group was not diagnosed with OSA, AHI less than 5 (non-OSA control). Anthropometric measurements such as lower face height (LFH), interincisial distance, nose height, anterior neck height (ANH), lateral neck height, posterior neck height (PNH), ramus mandible height, corpus mandible height (CML), bigonial distance (BGD), neck width, and neck depth were assessed.

Results: Patients with OSA had higher body mass index (BMI) and larger LFH, ANH, thyromental distance, CML, BGD, and neck circumference than those without OSA (p < 0.0001, p < 0.0001, p < 0.0001, p < 0.0001, p < 0.0001, p = 0.023, p < 0.0001, respectively). There was no difference between the two groups in terms of other parameters.

Conclusions: In this study, it was determined that BMI, lower face height, neck height, mandible length, bigonial width, thyromental distance and neck circumference are in significant relationship with sleep disordered breathing. Thus, these measurements may be used in clinical practice for prediction of OSA.

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Coronary artery dominance dependent collateral development in the human heart

Background: In obstructive coronary artery disease, coronary collateral arteries serve as alternative conduits for blood flow to the myocardial tissue supplied by the obstructed vessel(s). Therefore, they are a "natural coronary arterial bypass" to the region supplied by the obstructed vessels. This study aims to determine the influence of demographic and morphologic coronary arterial factors on coronary collateral development in coronary arterial obstruction.

Materials and methods: The study group was selected from the coronary angiographic records of 2029 consecutive patients (mean age: 59 ± 12 years). Coronary collaterals were graded from 0 to 3 based on the collateral connection between the donor and recipient arteries. The angiograms of the patients (n = 286) with total obstruction of the coronary arteries were selected for analysis.

Results: There were no significant association between patients' age and sex and the formation of excellent collaterals. However, the location of atherosclerotic lesion affected collateral development in the right coronary artery. In addition, the right coronary arterial dominant pattern significantly influenced the formation of excellent coronary collaterals.

Conclusions: Coronary collateral arteries are better developed in right dominant pattern. It may be concluded that coronary arterial morphological pattern influences coronary collateral artery development.

http://ift.tt/2skiFt4

Ectopic arachnoid granulation involving a rare intracranial venous sinus variant

Arachnoid granulations are hypertrophied arachnoid villi, which extend from the subarachnoid space into the venous system and aid in the passive filtration and reabsorption of cerebrospinal fluid. These macroscopic structures have been described in various locations, with the transverse and sigmoid sinuses seen as normal variants on imaging. Here we present the occurrence of an enlarged arachnoid granulation at the foramen rotundum where a variant intracranial venous sinus was identified during routine dissection. Variations, such as the one described herein, should be recognised by those who operate or interpret images of the skull base.

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Anatomic assessment of the left main bifurcation and dynamic bifurcation angles using computed tomography angiography

Background: An understanding of the left main coronary artery (LMCA) anatomy is important for accurate diagnosis and therapy. We aimed to investigate LMCA anatomy via 128-multisliced coronary computed-tomography-angiography (CCTA) in patients with normal LMCA.

Materials and methods: A total of 201 CCTA studies were included in this study. Anatomical features of LMCA including cross-sectional areas of the LMCA ostial, LMCA distal, left anterior descending artery (LAD) ostial and left circumflex artery (LCX) ostial, and degree of tapering and LMCA bifurcation angles (BA) in the form of LMCA-LCX BA, LMCA-LAD BA, LAD-LCX BA at end-diastole and end-systole.

Results: The mean age was 55 ± 11; 55.7% of patients were males. Right coronary artery was dominant in 173 (86.1%) patients. Mean LMCA length was 10.0 ± 4.5 mm. The mean values of LMCA ostial, LMCA distal, LAD ostial and LCX ostial areas were 18.2 ± 5.1 mm², 13.2 ± 4.0 mm², 9.0 ± 3.2 mm² and 7.6 ± ± 2.8 mm², respectively. LMCA ostial-distal area, LMCA distal-LAD ostial area and LMCA distal-LCX ostial area ratios were ≥ 1.44 – < 1.69 in 47 (23.4%), 53 (26.4%), 47 (23.4%) patients, respectively, and were ≥ 1.69 – < 1.96 in 19 (9.5%), 24 (11.9%), 40 (19.9%) patients respectively. Systolic motion modifies LMCA BAs; systolic motion begets an increment of LMCA-LAD angle in 72.6% of patients and decrement of LAD-LCX angle in 75.6% of patients. Patients with T-shaped LAD-LCX BA was shown to have significantly longer LMCA, larger LAD ostial area, larger LCX ostial area and higher diastolic-to-systolic range (DSR) of LAD-LCX BA compared to patients with Y-shaped LAD-LCX BA.

Conclusions: LMCA with T-shaped distal BA was found to have significantly longer LMCA, larger LAD ostial area, larger LCX ostial area and higher DSR of distal BA compared to patients with Y-shaped distal BA. These findings may provide useful information for LMCA bifurcation stenting or designing dedicated stents for LMCA.

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The report on the co-occurrence of two different rare anatomic variations of the plantaris muscle tendon on both sides of an individual

The plantaris muscle usually begins with a short and small muscle belly on the popliteal surface of the femur and on the knee joint capsule. It continues distally to form a long and thin tendon typically fixed to the calcaneal tuberosity. However, the course and the insertion of the plantaris muscle is variable, which may influence the development of Achilles tendinopathy. The plantaris tendon may also be used for reconstruction of tendons and ligaments, such as talofibular and calcaneofibular ligament. In literature review no data concerning the co-occurrence of anatomic variations of the plantaris muscle tendon in different individuals has been found. This report presents a rare variant of the plantaris muscle insertion into the deep crural fascia on the left leg and absence of the plantaris muscle on the right leg of the same individual.

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Congenital coronary artery anomalies in adult population detected using dual source ECG-gated CTA in a single institution

Background: Congenital anomalies of the coronary arteries (CAs) are rare and are often diagnosed incidentally during a conventional coronary angiography. Recently, the incidence of these congenital defects is on the rise particularly after the introduction of the electrocardiography (ECG) gated coronary computed tomographic angiography (CCTA). This innovative radiological screening modality has led to the most precise mapping of the course of the CAs on computed tomographic scan. The aim of the study is to determine the prevalence and describe the CAs congenital anomalies and their variations in Kuwaiti population at a single institution experience.

Materials and methods: We analysed the CCTA data obtained consecutively from 842 patients (2013–2014), retrospectively. The inclusion criteria for patients' selection were: atypical chest pain, equivocal ECG, assessment of patency of coronary stents or grafts and pre-operative screening. Information was acquiesced using a dual-source CT scanner with ECG gating.

Results: Data analysis revealed that 22 (2.61%) patients were found to have CA anomalies out of the 842 patients who underwent CCTA. Out of these CA anomalies, 13 cases showed more than two ostia, 7 cases showed the ectopic origin of a CA from opposite sinus or non-aortic sinus, 2 cases showed single coronary ostium and 1 case showed coronary artery with pulmonary fistula. Also, myocardial bridging was identified in 78 (9.26%) patients whereas ramus intermedius branch was identified in 160 (19%) patients.

Conclusions: The prevalence of CA anomalies in Kuwait was 2.6%, which is relatively higher than previously reported studies from different countries.

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Antler velvet is thicker in adult than in yearling pampas deer (Ozotoceros bezoarticus): a histological study

Background: Antlers are lined by soft velvet tissue during antler growth. Later, the velvet is shed before rut onset. There are no detailed histological descriptions of the growing velvet, nor whether the velvet changes according to stag age. Our aims were to: 1) describe the basic histology of pampas deer antler velvet from adult and yearling males; and 2) determine the influence of age and time of antler growth on velvet's tissues morphometry.

Materials and methods: Samples were collected from 10 stags allocated in two groups, either adult (3–5 years old, n = 5) or yearling males (2 years old, n = 5). The day of antler cast was recorded for each animal. In spring, the stags were anaesthetised and velvet samples were collected from the third tine's distal end. Samples were described qualitatively and a restricted morphometrical analysis of the antler velvet was performed.

Results: The number of keratinocyte layers and the thicknesses of: total epidermis, corneum, intermediate and basale epidermal strata, total dermis, superficial and deep dermis were determined. Age and days after antler casting positively influenced in conjunction epidermal thickness (p = 0.037), and tended to influence both stratum intermedium (p = 0.076) and stratum corneum (p = 0.1) thicknesses. Age influenced stratum corneum thickness (p = 0.04). The pampas deer antler velvet lacked both sweat glands and arrector pili muscles.

Conclusions: The deep dermis was densely irrigated but displayed abundant and well developed collagen bundles. Both total epidermal and stratum corneum thicknesses related positively to the age of the animals but were not to the time since antler cast.  

http://ift.tt/2rmeCim

An anatomical investigation of the superficial and deep palmar arches

Background: The superficial palmar arch (SPA) and deep palmar arch (DPA) provide the dominant vascular supply to the hand. The SPA is considered to be highly variable and can be classified as either complete or incomplete. The simplest definition states that the anastomosis between the vessels contributing to the arch represent a complete arch, while an incomplete arch is described as characterised by an absence of anastomosis between the vessels contributing to it. This study aimed to describe the anatomical landmarks, formation and branching patterns of the SPA and DPA. In this study, the SPA and DPA were dissected in 50 specimens (n = 100 adult hands), respectively.

Materials and methods: A complete SPA was observed in 92% of specimens and classified into three types. In Type A (44%), the SPA was formed by the anastomosis of the superficial palmar branch of the radial artery with the ulnar artery. Type B (46%) was formed by the ulnar artery alone and Type C (2%) was formed by anastomosis of the ulnar artery with the superficial palmar branch of the radial artery and the persistent median artery.

Results: An incomplete SPA was observed in 8% of the specimens and divided into three types formed by the radial and ulnar arteries. The DPA was divided into five types viz. Type G (72%), where the DPA was formed by anastomosis of the deep palmar branch of the radial artery (DPBRA) with the deep palmar branch of the ulnar artery (DPBUA). Type H (12%), was formed by anastomosis of the DPBRA, the DBUA and the interosseous artery. Type I (8%), was formed by the anastomosis of the DPBRA with the superior and inferior DPBUA. Type J (4%), the deep ulnar artery had two branches whereby either one branch anastomosed with the DPBRA to form the DPA. Type K (4%), the DBUA exhibited two deep branches with one branch anastomosing with the DPBRA to complete the DPA.

Conclusions: The interosseous artery anastomosed with either the DPA or the additional DPBUA. Knowledge of the variability of the SPA and DPA is crucial for safe and successful hand surgeries.  

http://ift.tt/2sk9MzH

Anatomy of the long peroneal muscle of the leg

Background: The aim of the work was to perform a morphometric analysis of the long peroneal muscle (LPM) of the leg and explore the relationship between muscle belly and tendon.

Materials and methods: Ten lower limbs (8 right and 2 left) were fixed in formaldehyde and dissected using standard technique. The LPM was exposed from the proximal attachment to the top of a lateral malleolus.

Results: The tendon was subsequently freed and various measurements were taken. The tendon of the LPM enters deep into the muscle belly. Muscle fibres surround the tendon and descend as far down as 4 cm above the lateral malleolus. Muscle fibres insert mainly along posterior border of the tendon and on its medial surface, leaving lateral surface only partly covered.

Conclusions: The LPM contains a long intramuscular segment of the tendon and area of the musculotendinous junction varies along the LPM. It makes the idea of uniform pennation pattern of the LPM unlikely  

http://ift.tt/2rmbvXY

Quality of life after radiotherapy for prostate cancer with a hydrogel spacer – five year results

Spacers are increasingly placed between the prostate and rectal wall before prostate cancer radiotherapy. Long-term clinical results are needed to better define a possible benefit for patients. The first five-year quality of life results in a group of prostate cancer patients treated with a hydrogel spacer demonstrate excellent treatment tolerability, in particular regarding bowel problems, superior to the results of a control group treated conventionally.

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Hymenolepis nana infection detected by magnifying colonoscopy with narrow-band imaging (with video)

http://ift.tt/2rmaVJP

Diffuse gastric metastases from salivary duct carcinoma

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Cronkhite-Canada syndrome

http://ift.tt/2rlUkpq

Successful endoscopic submucosal dissection for superficial esophageal cancer on solitary esophageal varix

http://ift.tt/2sjOhyP

Molecular analysis of sentinel lymph node in colon carcinomas by one-step nucleic acid amplification (OSNA) reduces time to adjuvant chemotherapy interval

The interval between surgery and adjuvant chemotherapy (AC) is a predictive factor of survival in high-risk colon cancer (CC). This study aimed to evaluate the impact of intraoperative sentinel lymph node (SLN) analysis using the one-step nucleic acid amplification (OSNA) technique on the time interval between surgery and AC.

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An unusual cause of biliary metal stent obstruction

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Measuring VLDL1-Triglyceride and VLDL2-Triglyceride Kinetics in Men: Effects of Dietary Control on Day-to-Day Variability

Horm Metab Res
DOI: 10.1055/s-0043-109561

The aim of this study was to assess the impact of dietary control on VLDL1- and VLDL2-TG kinetics and associated metabolic parameters. Twelve overweight/obese men were randomized to a provided 3 day isocaloric diet with fixed macronutrient composition (diet group, n=6) or to their regular unrestricted diet (non-diet group, n=6). VLDL1- and VLDL2-TG turnovers were measured twice 2–4 weeks apart, using primed-constant infusion of ex vivo labeled [1-14C]VLDL1-TG and [9,10-3H]VLDL2-TG. Isocaloric diet intervention lowered the difference in the mean of both VLDL2-TG secretion and clearance rate (p<0.01), and the coefficient of variation (CV) of VLDL2-TG clearance rate (p<0.05). The difference in mean and CV of the other kinetic estimates (VLDL1-TG secretion, clearance and oxidation rate) were lowered, but not significantly. The CV's of total triglyceride, VLDL1-TG, and VLDL2-TG concentrations were significantly lowered by diet intervention compared to regular diet; total triglyceride (31%–5%, p<0.01), VLDL1-TG (42%–9%, p<0.01), and VLDL2-TG (36%–10%, p<0.01). In conclusion, VLDL1- and VLDL2-TG kinetics show great day-to-day variability, which may be diminished by diet intervention. Therefore, standardized macronutrient intake prior to study days improves the probability of demonstrating significant outcomes of cross-sectional and intervention studies of VLDL1-TG and VLDL2-TG kinetics and metabolism.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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Salivary Cortisol, Perceived Stress, and Metabolic Syndrome: A Matched Case-Control Study in Female Shift Workers

Horm Metab Res
DOI: 10.1055/s-0043-101822

Although the pathogenesis of metabolic syndrome (MetS) is complex and multifactorial, there is limited information if psychological factors, such as stress exposure, are involved in the etiology of MetS. Therefore, this study investigated the associations between MetS and cortisol levels and perceived stress levels among women shift workers in Southern Brazil. A matched case-control study was conducted, including 50 cases of MetS and 200 age-matched controls (±3 years, 4 for each case). Salivary cortisol levels were evaluated immediately after waking and one upon returning home from work. Perceived stress levels were measured by the Perceived Stress Scale with 10 items (PSS-10). Multivariate-adjusted associations between MetS and salivary cortisol levels and perceived stress levels were assessed by conditional logistic regression. Means±standard deviations of salivary cortisol levels were not significantly different between cases and controls either immediately after waking (5.37±4.10 vs. 6.03±5.39 nmol/l; p = 0.53) or after work (2.74±2.87 vs. 2.78±2.85 nmol/l; p = 0.93). There was no significant difference in perceived stress level between cases and controls (14.2±5.9 vs. 15.5±5.6; p = 0.15). No independent association was observed in the multivariate model between MetS and salivary cortisol level or perceived stress level after these exposures were stratified into tertiles. Overall, there was no difference between women with or without MetS in regard to the free salivary cortisol and perceived stress. Our results do not support an association between stress exposure and MetS among women shift workers.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

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High Leptin Level Attenuates Embryo Development in Overweight/Obese Infertile Women by Inhibiting Proliferation and Promotes Apoptosis in Granule Cell

Horm Metab Res
DOI: 10.1055/s-0043-107617

Obesity appears to be associated with female reproductive dysfunction and infertility. Women with obesity undergoing in vitro fertilization (IVF) had poor oocyte quality, decreased embryo development, and poor pregnancy outcome. However, the mechanism linking obesity to poor reproductive outcomes is still unclear. Obesity is frequently accompanied with elevated leptin levels. Here we aimed to evaluate the effect of high leptin level in follicular fluid (FF) on the proliferation and apoptosis in granule cells and correlate these findings with poor reproductive outcomes in infertile women with overweight or obesity who underwent IVF treatment. We investigated clinical and ongoing pregnancy rates in 189 infertile women who underwent IVF. Leptin levels were quantified in peripheral blood and FF as well. In vitro cell model was used to explore the potential effect of high leptin on the proliferation and apoptosis in granulosa cells. Results showed reduced clinical and ongoing pregnancy rates in overweight/obesity women who underwent IVF compared to control with normal BMI. On the other hand, leptin levels presented significant increase in peripheral blood and FF in overweight/obese women. Leptin level in FF was negatively correlated to good quality embryo rate. Importantly, in vitro study showed that leptin inhibited cells proliferation and promoted apoptosis by upregulation of caspase-3 and downregulation of Bcl-2 in granulosa cells in a dose dependent manner. These observations suggest that leptin may acts as a local mediator to attenuate embryo development and reduce fertility in obese patients.
[...]

© Georg Thieme Verlag KG Stuttgart · New York

Article in Thieme eJournals:
Table of contents  |  Abstract  |  Full text

http://ift.tt/2rlVMbu

Retraction statement: Mathematical-based modeling and prediction of the effect of external stimuli on human gait

http://ift.tt/2r9cv0T

Demonstration of biological activities of extracts from Isodon rugosus Wall. Ex Benth: Separation and identification of bioactive phytoconstituents by GC-MS analysis in the ethyl acetate extract

Since long, natural sources have been explored for possible managements of various diseases. In this context, the study is designed to evaluate Isodon rugosus Wall. ex Benth for biological potentials including an...

http://ift.tt/2rCA6so

Inhibition of biofilm formation in Mycobacterium smegmatis by Parinari curatellifolia leaf extracts

Tuberculosis (TB) is a serious public health problem worldwide. Mycobacterium tuberculosis (M. tuberculosis) grows as drug tolerant pellicles. Agents that inhibit biofilm formation in M. tuberculosis have the pot...

http://ift.tt/2sbOLaW

Occurrence of BAP1 germline mutations in cutaneous melanocytic tumors with loss of BAP1-expression: a pilot study

Abstract

Melanocytic BAP1-associated intradermal tumors (MBAITs) can either be sporadic or associated with a cancer-predisposition syndrome. In this study we explored the clinical status of 136 patients in which at least one MBAIT was found. 49/136 (36%) of them gave their signed consent for an oncogenetic BAP1 blood test. 28/136 patients (20%) diagnosed with an MBAIT had other MBAITs and/or a personal or familial history of BAP1-related cancers that could clinically designate them as potential carriers of a BAP1 germline mutation. 17 of these 28 patients underwent oncogenetic testing. A deleterious mutation of BAP1 was confirmed in 12/17 cases. 4/17 cases were wild-type; all had a single MBAIT and a history of skin melanoma. A variant of unknown significance was found in one case with multiple MBAITs. Among the 12 mutated cases, multiple MBAITs were present in 10/12 cases and were the only clinical sign in 4/12 cases. The remaining 32/49 blood-tested cases with an isolated MBAIT were wild type for BAP1 in 25/32 cases or showed a variant of unknown significance in 7/32 cases. We recommend, following the diagnosis of a MBAIT, performing a BAP1 immunohistochemistry in all other cutaneous melanocytic tumors removed previously or simultaneously and all skin melanomas. This screening could help clinicians prioritize which patients would most benefit from oncogenetic testing. This article is protected by copyright. All rights reserved.

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Towards standardization of 18 F-FET PET imaging: do we need a consistent method of background activity assessment?

Abstract

Background

PET with O-(2-¹⁸F-fluoroethyl)-L-tyrosine (¹⁸F-FET) has reached increasing clinical significance for patients with brain neoplasms. For quantification of standard PET-derived parameters such as the tumor-to-background ratio, the background activity is assessed using a region of interest (ROI) or volume of interest (VOI) in unaffected brain tissue. However, there is no standardized approach regarding the assessment of the background reference. Therefore, we evaluated the intra- and inter-reader variability of commonly applied approaches for clinical ¹⁸F-FET PET reading.

The background activity of 20 ¹⁸F-FET PET scans was independently evaluated by 6 readers using a (i) simple 2D-ROI, (ii) spherical VOI with 3.0 cm diameter, and (iii) VOI consisting of crescent-shaped ROIs; each in the contralateral, non-affected hemisphere including white and gray matter in line with the European Association of Nuclear Medicine (EANM) and German guidelines. To assess intra-reader variability, each scan was evaluated 10 times by each reader. The coefficient of variation (CoV) was assessed for determination of intra- and inter-reader variability. In a second step, the best method was refined by instructions for a guided background activity assessment and validated by 10 further scans.

Results

Compared to the other approaches, the crescent-shaped VOIs revealed most stable results with the lowest intra-reader variabilities (median CoV 1.52%, spherical VOI 4.20%, 2D-ROI 3.69%; p < 0.001) and inter-reader variabilities (median CoV 2.14%, spherical VOI 4.02%, 2D-ROI 3.83%; p = 0.001). Using the guided background assessment, both intra-reader variabilities (median CoV 1.10%) and inter-reader variabilities (median CoV 1.19%) could be reduced even more.

Conclusions

The commonly applied methods for background activity assessment show different variability which might hamper ¹⁸F-FET PET quantification and comparability in multicenter settings. The proposed background activity assessment using a (guided) crescent-shaped VOI allows minimization of both intra- and inter-reader variability and might facilitate comprehensive methodological standardization of amino acid PET which is of interest in the light of the anticipated EANM technical guidelines.

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Monitoring response to anti-angiogenic mTOR inhibitor therapy in vivo using 111 In-bevacizumab

Abstract

Background

The ability to image vascular endothelial growth factor (VEGF) could enable prospective, non-invasive monitoring of patients receiving anti-angiogenic therapy. This study investigates the specificity and pharmacokinetics of ¹¹¹In-bevacizumab binding to VEGF and its use for assessing response to anti-angiogenic therapy with rapamycin.

Specificity of ¹¹¹In-bevacizumab binding to VEGF was tested in vitro with unmodified radiolabelled bevacizumab in competitive inhibition assays. Uptake of ¹¹¹In-bevacizumab in BALB/c nude mice bearing tumours with different amounts of VEGF expression was compared to that of isotype-matched control antibody (¹¹¹In-IgG1κ) with an excess of unlabelled bevacizumab. Intratumoural VEGF was evaluated using ELISA and Western blot analysis. The effect of anti-angiogenesis therapy was tested by measuring tumour uptake of ¹¹¹In-bevacizumab in comparison to ¹¹¹In-IgG1κ following administration of rapamycin to mice bearing FaDu xenografts. Uptake was measured using gamma counting of ex vivo tumours and effect on vasculature by using anti-CD31 microscopy.

Results

Specific uptake of ¹¹¹In-bevacizumab in VEGF-expressing tumours was observed. Rapamycin led to tumour growth delay associated with increased relative vessel size (8.5 to 10.3, P = 0.045) and decreased mean relative vessel density (0.27 to 0.22, P = 0.0015). Rapamycin treatment increased tumour uptake of ¹¹¹In-bevacizumab (68%) but not ¹¹¹In-IgGκ and corresponded with increased intratumoural VEGF₁₆₅.

Conclusions

¹¹¹In-bevacizumab accumulates specifically in VEGF-expressing tumours, and changes after rapamycin therapy reflect changes in VEGF expression. Antagonism of mTOR may increase VEGF in vivo, and this new finding provides the basis to consider combination studies blocking both pathways and a way to monitor effects.

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FDA Approves First Generic Strattera for the Treatment of ADHD

May 30, 2017 -- The U.S. Food and Drug Administration today approved the first generic versions of Strattera (atomoxetine) to treat attention-deficit/hyperactivity disorder (ADHD) in pediatric and adult patients. Apotex Inc., Teva Pharmaceuticals...

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Hydrogen-rich water alleviates the toxicities of different stresses to mycelial growth in Hypsizygus marmoreus

In plants, hydrogen gas (H2) enhances tolerance to several abiotic stresses, including salinity and heavy metals. However, the effect of H2 on fungal growth under different stresses remains largely unclear. In th...

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Simulation Modelling in Healthcare: An Umbrella Review of Systematic Literature Reviews

Abstract

Background

Numerous studies examine simulation modelling in healthcare. These studies present a bewildering array of simulation techniques and applications, making it challenging to characterise the literature.

Objective

The aim of this paper is to provide an overview of the level of activity of simulation modelling in healthcare and the key themes.

Methods

We performed an umbrella review of systematic literature reviews of simulation modelling in healthcare. Searches were conducted of academic databases (JSTOR, Scopus, PubMed, IEEE, SAGE, ACM, Wiley Online Library, ScienceDirect) and grey literature sources, enhanced by citation searches. The articles were included if they performed a systematic review of simulation modelling techniques in healthcare. After quality assessment of all included articles, data were extracted on numbers of studies included in each review, types of applications, techniques used for simulation modelling, data sources and simulation software.

Results

The search strategy yielded a total of 117 potential articles. Following sifting, 37 heterogeneous reviews were included. Most reviews achieved moderate quality rating on a modified AMSTAR (A Measurement Tool used to Assess systematic Reviews) checklist. All the review articles described the types of applications used for simulation modelling; 15 reviews described techniques used for simulation modelling; three reviews described data sources used for simulation modelling; and six reviews described software used for simulation modelling. The remaining reviews either did not report or did not provide enough detail for the data to be extracted.

Conclusion

Simulation modelling techniques have been used for a wide range of applications in healthcare, with a variety of software tools and data sources. The number of reviews published in recent years suggest an increased interest in simulation modelling in healthcare.

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Comparison of glass slides and various digital-slide modalities for cytopathology screening and interpretation

BACKGROUND

Whole-slide imaging in cytology is limited when glass slides are digitized without z-stacks for focusing. Different vendors have started to provide z-stacking solutions to overcome this limitation. The Panoptiq imaging system allows users to create digital files combining low-magnification panoramic images with regions of interest (ROIs) that are imaged with high-magnification z-stacks. The aim of this study was to compare such panoramic images with conventional whole-slide images and glass slides for the tasks of screening and interpretation in cytopathology.

METHODS

Thirty glass slides, including 10 ThinPrep Papanicolaou tests and 20 nongynecologic cytology cases, were digitized with an Olympus BX45 integrated microscope with an attached Prosilica GT camera. ViewsIQ software was used for image acquisition and viewing. These glass slides were also scanned on an Aperio ScanScope XT at ×40 (0.25 μm/pixel) with 1 z-plane and were viewed with ImageScope software. Digital and glass sides were screened and dotted/annotated by a cytotechnologist and were subsequently reviewed by 3 cytopathologists. For panoramic images, the cytotechnologist manually created digital maps and selected representative ROIs to generate z-stacks at a higher magnification. After 3-week washout periods, panoramic images were compared with Aperio digital slides and glass slides.

RESULTS

The Panoptiq system permitted fine focusing of thick smears and cell clusters. In comparison with glass slides, the average screening times were 5.5 and 1.8 times longer with Panoptiq and Aperio images, respectively, but this improved with user experience. There was no statistical difference in diagnostic concordance between all 3 modalities. Users' diagnostic confidence was also similar for all modalities.

CONCLUSIONS

The Aperio whole-slide scanner with 1 z-plane scanning and the Panoptiq imaging system with z-stacking are both suitable for cytopathology screening and interpretation. However, ROI z-stacks do offer a superior mechanism for overcoming focusing problems commonly encountered with digital cytology slides. Unlike whole-slide imaging, the acquisition of representative z-stack images with the Panoptiq system requires a trained cytologist to create digital files. Cancer Cytopathol 2017. © 2017 American Cancer Society.

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A numerical investigation and experimental verification of size effects in loaded bovine cortical bone

Abstract

In this paper we present two and three dimensional finite element based numerical models of loaded bovine cortical bone that explicitly incorporate the dominant microstructural feature: the vascular channel or Haversian canal system. The finite element models along with the representation of the microstructure within them are relatively simple: two dimensional models, consisting of a structured mesh of linear elastic planar elements punctuated by a periodic distribution of circular voids, are used to represent beam samples of cortical bone in which the channels are orientated perpendicular to the sample major axis, while three dimensional models, employing a corresponding mesh of equivalent solid elements, represent those samples in which the canals are aligned with the axis. However, these models are exploited in an entirely novel approach involving the representation of material samples of different sizes and surface morphology. The numerical results obtained for the virtual material samples when loaded in bending indicate that they exhibit size effects not forecast by either classical (Cauchy) or more generalized elasticity theories. However, these effects are qualitatively consistent with those that we observed in a series of carefully conducted experiments involving the flexural testing of bone samples of different sizes. Encouraged by this qualitative agreement we have identified appropriate model parameters, primarily void volume fraction but also void separation and matrix modulus by matching the computed size effects to those we observed experimentally. Interestingly, the parameter choices that provide the most suitable match of these effects broadly concur with those we actually observed in cortical bone.

http://ift.tt/2rS8Q93

SpF PLUS-Mini and SpF XL IIB Implantable Spinal Fusion Stimulators by Zimmer Biomet: Class I Recall - Potential for Harmful Chemicals

Audience: Risk Manager, Orthopedics, Patient, Surgery [Posted 05/30/2017] ISSUE: Zimmer Biomet is recalling the SpF PLUS-Mini and SpF XL IIb Implantable Spinal Fusion Stimulators due to higher than allowed levels of potential harmful chemicals,...

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Long-term HIF-1{alpha} transcriptional activation is essential for heat-acclimation-mediated cross tolerance: mitochondrial target genes

An important adaptive feature of heat acclimation (HA) is the induction of cross tolerance against novel stressors (HACT) Reprogramming of gene expression leading to enhanced innate cytoprotective features by attenuating damage and/or enhancing the response of "help" signals plays a pivotal role. Hypoxia-inducible factor-1α (HIF-1α), constitutively upregulated by HA (1 mo, 34°C), is a crucial transcription factor in this program, although its specific role is as yet unknown. By using a rat HA model, we studied the impact of disrupting HIF-1α transcriptional activation [HIF-1α:HIF-1β dimerization blockade by intraperitoneal acriflavine (4 mg/kg)] on its mitochondrial gene targets [phosphoinositide-dependent kinase-1 (PDK1), LON, and cyclooxygenase 4 (COX4) isoforms] in the HA rat heart. Physiological measures of cardiac HACT were infarct size after ischemia-reperfusion and time to rigor contracture during hypoxia in cardiomyocytes. We show that HACT requires transcriptional activation of HIF-1α throughout the course of HA and that this activation is accompanied by two metabolic switches: 1) profound upregulation of PDK1, which reduces pyruvate entry into the mitochondria, consequently increasing glycolytic lactate production; 2) remodeling of the COX4 isoform ratio, inducing hypoxic-tolerant COX4.2 dominance, and optimizing electron transfer and possibly ATP production during the ischemic and hypoxic insults. LON and COX4.2 transcript upregulation accompanied this shift. Loss of HACT despite elevated expression of the cytoprotective protein heat shock protein-72 concomitantly with disrupted HIF-1α dimerization suggests that HIF-1α is essential for HACT. The role of a PDK1 metabolic switch is well known in hypoxia acclimation but not in the HA model and its ischemic setting. Remodeling of COX4 isoforms by environmental acclimation is a novel finding.

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Exocytosis proteins as novel targets for diabetes prevention and/or remediation?

Diabetes remains one of the leading causes of morbidity and mortality worldwide, affecting an estimated 422 million adults. In the US, it is predicted that one in every three children born as of 2000 will suffer from diabetes in their lifetime. Type 2 diabetes results from combinatorial defects in pancreatic β-cell glucose-stimulated insulin secretion and in peripheral glucose uptake. Both processes, insulin secretion and glucose uptake, are mediated by exocytosis proteins, SNARE (soluble N-ethylmaleimide-sensitive factor attachment protein receptor) complexes, Sec1/Munc18 (SM), and double C2-domain protein B (DOC2B). Increasing evidence links deficiencies in these exocytosis proteins to diabetes in rodents and humans. Given this, emerging studies aimed at restoring and/or enhancing cellular levels of certain exocytosis proteins point to promising outcomes in maintaining functional β-cell mass and enhancing insulin sensitivity. In doing so, new evidence also shows that enhancing exocytosis protein levels may promote health span and longevity and may also harbor anti-cancer and anti-Alzheimer's disease capabilities. Herein, we present a comprehensive review of the described capabilities of certain exocytosis proteins and how these might be targeted for improving metabolic dysregulation.

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The roles of KCa, KATP, and KV channels in regulating cutaneous vasodilation and sweating during exercise in the heat

We recently showed the varying roles of Ca²⁺-activated (K_Ca), ATP-sensitive (K_ATP), and voltage-gated (K_V) K⁺ channels in regulating cholinergic cutaneous vasodilation and sweating in normothermic conditions. However, it is unclear whether the respective contributions of these K⁺ channels remain intact during dynamic exercise in the heat. Eleven young (23 ± 4 yr) men completed a 30-min exercise bout at a fixed rate of metabolic heat production (400 W) followed by a 40-min recovery period in the heat (35°C, 20% relative humidity). Cutaneous vascular conductance (CVC) and local sweat rate were assessed at four forearm skin sites perfused via intradermal microdialysis with: 1) lactated Ringer solution (control); 2) 50 mM tetraethylammonium (nonspecific K_Ca channel blocker); 3) 5 mM glybenclamide (selective K_ATP channel blocker); or 4) 10 mM 4-aminopyridine (nonspecific K_V channel blocker). Responses were compared at baseline and at 10-min intervals during and following exercise. K_Ca channel inhibition resulted in greater CVC versus control at end exercise (P = 0.04) and 10 and 20 min into recovery (both P < 0.01). K_ATP channel blockade attenuated CVC compared with control during baseline (P = 0.04), exercise (all P ≤ 0.04), and 10 min into recovery (P = 0.02). No differences in CVC were observed with K_V channel inhibition during baseline (P = 0.15), exercise (all P ≥ 0.06), or recovery (all P ≥ 0.14). With the exception of K_V channel inhibition augmenting sweating during baseline (P = 0.04), responses were similar to control with all K⁺ channel blockers during each time period (all P ≥ 0.07). We demonstrated that K_Ca and K_ATP channels contribute to the regulation of cutaneous vasodilation during rest and/or exercise and recovery in the heat.

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Impact of lifelong exercise training on endothelial ischemia-reperfusion and ischemic preconditioning in humans

Reperfusion is essential for ischemic tissue survival, but causes additional damage to the endothelium [i.e., ischemia-reperfusion (I/R) injury]. Ischemic preconditioning (IPC) refers to short repetitive episodes of ischemia that can protect against I/R. However, IPC efficacy attenuates with older age. Whether physical inactivity contributes to the attenuated efficacy of IPC to protect against I/R injury in older humans is unclear. We tested the hypotheses that lifelong exercise training relates to 1) attenuated endothelial I/R and 2) maintained IPC efficacy that protects veteran athletes against endothelial I/R. In 18 sedentary male individuals (SED, <1 exercise h/wk for >20 yr, 63 ± 7 yr) and 20 veteran male athletes (ATH, >5 exercise h/wk for >20 yr, 63 ± 6 yr), we measured brachial artery endothelial function with flow-mediated dilation (FMD) before and after I/R. We induced I/R by 20 min of ischemia followed by 20 min of reperfusion. Randomized over 2 days, participants underwent either 35-min rest or IPC (3 cycles of 5-min cuff inflation to 220 mmHg with 5 min of rest) before I/R. In SED, FMD decreased after I/R [median (interquartile range)]: [3.0% (2.0–4.7) to 2.1% (1.5–3.9), P = 0.046] and IPC did not prevent this decline [4.1% (2.6–5.2) to 2.8% (2.2–3.6), P = 0.012]. In ATH, FMD was preserved after I/R [3.0% (1.7–5.4) to 3.0% (1.9–4.1), P = 0.82] and when IPC preceded I/R [3.2% (1.9–4.2) to 2.8% (1.4–4.6), P = 0.18]. These findings indicate that lifelong exercise training is associated with increased tolerance against endothelial I/R. These protective, preconditioning effects of lifelong exercise against endothelial I/R may contribute to the cardioprotective effects of exercise training.

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Sex-specific differences in age-dependent progression of aortic dysfunction and related cardiac remodeling in spontaneously hypertensive rats

Evidence of sex-specific differences in renin-angiotensin-system (RAS) and arterial pressure has been shown in many mammals, including spontaneously hypertensive rats (SHRs). Although SHRs have been used extensively as a leading experimental model of hypertension, the effects of sex-specific differences in RAS on aortic function and related cardiac remodeling during aging and hypertension have not been documented in detail. We examined structural and functional changes in aorta and heart of female and male SHRs at the ages of 5, 14, 29, and 36 wk. SHRs of both sexes were hypertensive from 14 wk. Aortic endothelial dysfunction and fibrosis, left ventricular (LV) hypertrophy, and cardiac fibrosis were evident at the age of 29 wk in male SHRs but first appeared only at the age of 36 wk in female SHRs. There was a pronounced delay of matrix metalloproteinase-2 activity in the aorta and heart of female SHRs, which was associated with preservation of 40% more elastin and less extensive cardiac fibrosis than in males. At 5, 29, and 36 wk of age, female SHRs showed higher levels of aortic and myocardial AT₂R and MasR mRNA and decreased ANG II-mediated aortic constriction. Although female SHRs had increased relaxation to AT₂R stimulation at 5 and 29 wk compared with males, this difference disappeared at 36 wk of age. This study documents sex-specific differences in the temporal progression of aortic dysfunction and LV hypertrophy in SHRs, which are independent of arterial pressure and are apparently mediated by higher AT₂R expression in the heart and aorta of female SHRs.

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Reduced skeletal muscle fiber size following caloric restriction is associated with calpain-mediated proteolysis and attenuation of IGF-1 signaling

Caloric restriction decreases skeletal muscle mass in mammals, principally due to a reduction in fiber size. The effect of suboptimal nutrient intake on skeletal muscle metabolic properties in neonatal calves was examined. The longissimus muscle (LM) was collected after a control (CON) or caloric restricted (CR) diet was cosnumed for 8 wk and muscle fiber size, gene expression, and metabolic signal transduction activity were measured. Results revealed that CR animals had smaller (P < 0.05) LM fiber cross-sectional area than CON, as expected. Western blot analysis detected equivalent amounts of peroxisome proliferator-activated receptor- coactivator-1α (PGC1α) but reduced (P < 0.05) amounts of the splice-variant, PGC1α-4 in CR LM. Expression of IGF-1, a PGC1α-4 target gene, was 40% less (P < 0.05) in CR than CON. Downstream mediators of autocrine IGF-1 signaling also are attenuated in CR by comparison with CON. The amount of phosphorylated AKT1 was less (P < 0.05) in CR than CON. The ratio of p4EBP1^T37/46 to total 4EBP1, a downstream mediator of AKT1, did not differ between CON and CR. By contrast, protein lysates from CR LM contained less (P < 0.05) total glycogen synthase kinase-3β (GSK3β) and phosphorylated GSK3β than CON LM, suggesting blunted protein synthesis. Smaller CR LM fiber size associates with increased (P < 0.05) calpain 1 (CAPN1) activity coupled with lower (P < 0.05) expression of calpastatin, the endogenous inhibitor of CAPN1. Atrogin-1 and MuRF expression and autophagy components were unaffected by CR. Thus CR suppresses the hypertrophic PGC1α-4/IGF-1/AKT1 pathway while promoting activation of the calpain system.

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Variable reliability of surrogate measures of insulin sensitivity after Roux-en-Y gastric bypass

Roux-en-Y gastric bypass (RYGB) induces weight loss and improves insulin sensitivity when evaluated by the hyperinsulinemic-euglycemic clamp (HEC). Surrogate indices of insulin sensitivity calculated from insulin and glucose concentrations at fasting or after an oral glucose tolerance test (OGTT) are frequently used, but have not been validated after RYGB. Our aim was to evaluate whether surrogate indices reliably estimate changes in insulin sensitivity after RYGB. Four fasting surrogates (inverse-HOMA-IR, HOMA2-%S, QUICKI, revised-QUICKI) and three OGTT-derived surrogates (Matsuda, Gutt, OGIS) were compared with HEC-estimated peripheral insulin sensitivity (R_d or R_d/I, depending on how the index was originally validated) and the tracer-determined hepatic insulin sensitivity index (HISI) in patients with preoperative type 2 diabetes (n = 10) and normal glucose tolerance (n = 10) 1 wk, 3 mo, and 1 yr postoperatively. Post-RYGB changes in inverse-HOMA-IR and HOMA2-%S did not correlate with changes in R_d at any visit, but were comparable to changes in HISI at 1 wk. Changes in QUICKI and revised-QUICKI correlated with R_d/I after surgery. Changes in the Matsuda and Gutt indices did not correlate with changes in R_d/I and R_d, respectively, whereas OGIS changes correlated with R_d changes at 1 yr post-RYGB. In conclusion, surrogate measures of insulin sensitivity may not reflect results obtained with gold standard methodology after RYGB, underscoring the importance of critical reflection when surrogate endpoints are used. Fasting surrogate indices may be particularly affected by post-RYGB changes in insulin clearance, whereas the validity of OGTT-derived surrogates may be compromised by surgical rearrangements of the gut.

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Examination of carnitine palmitoyltransferase 1 abundance in white adipose tissue: implications in obesity research

Carnitine palmitoyltransferase 1 (CPT1) is essential for the transport of long-chain fatty acids into the mitochondria for oxidation. Recently, it was reported that decreased CPT1b mRNA in adipose tissue was a contributing factor for obesity in rats. We therefore closely examined the expression level of Cpt1 in adipose tissue from mice, rats, and humans. Cpt1a is the predominate isoform in adipose tissue from all three species. Rat white adipose tissue has a moderate amount of Cpt1b mRNA, but it is very minor compared with Cpt1b expression in muscle. Total CPT1 activity in adipose tissue is also minor relative to other tissues. Both Cpt1a and Cpt1b mRNA were increased in gonadal fat but not inguinal fat by diet-induced obesity in mice. We also measured CPT1a and CPT1b expression in subcutaneous adipose tissue from human subjects with a wide range of body mass indexes (BMIs). Interestingly, CPT1a expression positively correlated with BMI (R = 0.46), but there was no correlation with CPT1b (R = 0.04). Our findings indicate that white adipose tissue fatty acid oxidation capacity is minor compared with that of metabolically active tissues. Furthermore, given the already low abundance of Cpt1b in white adipose tissue, it is unlikely that decreases in its expression can quantitatively decrease whole body energy expenditure enough to contribute to an obese phenotype.

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Thermoregulatory inversion: a novel thermoregulatory paradigm

To maintain core body temperature in mammals, the normal central nervous system (CNS) thermoregulatory reflex networks produce an increase in brown adipose tissue (BAT) thermogenesis in response to skin cooling and an inhibition of the sympathetic outflow to BAT during skin rewarming. In contrast, these normal thermoregulatory reflexes appear to be inverted in hibernation/torpor; thermogenesis is inhibited during exposure to a cold environment, allowing dramatic reductions in core temperature and metabolism, and thermogenesis is activated during skin rewarming, contributing to a return of normal body temperature. Here, we describe two unrelated experimental paradigms in which rats, a nonhibernating/torpid species, exhibit a "thermoregulatory inversion," which is characterized by an inhibition of BAT thermogenesis in response to skin cooling, and a switch in the gain of the skin cooling reflex transfer function from negative to positive values. Either transection of the neuraxis immediately rostral to the dorsomedial hypothalamus in anesthetized rats or activation of A1 adenosine receptors within the CNS of free-behaving rats produces a state of thermoregulatory inversion in which skin cooling inhibits BAT thermogenesis, leading to hypothermia, and skin warming activates BAT, supporting an increase in core temperature. These results reflect the existence of a novel neural circuit that mediates inverted thermoregulatory reflexes and suggests a pharmacological mechanism through which a deeply hypothermic state can be achieved in nonhibernating/torpid mammals, possibly including humans.

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Longitudinal characterization of renal proximal tubular markers in normotensive and preeclamptic pregnancies

Glomerular damage is common in preeclampsia (PE), but the extent and etiology of tubular injury are not well understood. The aim of this study was to evaluate tubular injury in patients with PE and to assess whether it predates clinical disease. We performed a prospective cohort study of 315 pregnant women who provided urine samples at the end of the second trimester and at delivery. This analysis included women who developed PE (n = 15), gestational hypertension (GH; n = 14), and normotensive controls (NC; n = 44). Urinary markers of tubular injury, α1-microglobulin (A1M), retinol-binding protein (RBP), kidney-injury molecule-1 (KIM1), complement C5b-9, tissue inhibitor metalloproteinase-2 (TIMP-2), and insulin-like growth factor binding protein-7 (IGFBP-7) were measured by enzyme-linked immunosorbent assay (ELISA) and reported in relation to urine creatinine concentration. Second-trimester concentrations of all markers were similar among groups. At delivery, A1M concentrations were higher in the PE group than in the GH and NC groups as an A1M/creatinine ratio >13 (66.7, 8.3, and 35%, respectively, P = 0.01). Concentrations of C5b-9 were higher in the PE group than in the GH and NC groups (medians 9.85, 0.05, and 0.28 ng/mg, respectively, P = 0.003). KIM1, RBP, TIMP-2, and IGFBP-7 concentrations did not differ among groups at delivery. In conclusion, proximal tubular dysfunction, as assessed by A1M and C5b-9, developed during the interval between the end of the second trimester and delivery in patients with PE. However, this was not matched by abnormalities in markers previously associated with tubular cell injury (KIM-1, IGFBP-7, and TIMP-2).

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Aortic depressor nerve stimulation does not impede the dynamic characteristics of the carotid sinus baroreflex in normotensive or spontaneously hypertensive rats

Recent clinical trials in patients with drug-resistant hypertension indicate that electrical activation of the carotid sinus baroreflex can reduce arterial pressure (AP) for more than a year. To examine whether the electrical stimulation from one baroreflex system impedes normal short-term AP regulation via another unstimulated baroreflex system, we electrically stimulated the left aortic depressor nerve (ADN) while estimating the dynamic characteristics of the carotid sinus baroreflex in anesthetized normotensive Wistar-Kyoto (WKY; n = 8) rats and spontaneously hypertensive rats (SHR; n = 7). Isolated carotid sinus regions were perturbed for 20 min using a Gaussian white noise signal with a mean of 120 mmHg for WKY and 160 mmHg for SHR. Tonic ADN stimulation (2 Hz, 10 V, and 0.1-ms pulse width) decreased mean sympathetic nerve activity (73.4 ± 14.0 vs. 51.6 ± 11.3 arbitrary units in WKY, P = 0.012; and 248.7 ± 33.9 vs. 181.1 ± 16.6 arbitrary units in SHR, P = 0.018) and mean AP (90.8 ± 6.6 vs. 81.2 ± 5.4 mmHg in WKY, P = 0.004; and 128.6 ± 9.8 vs. 114.7 ± 10.3 mmHg in SHR, P = 0.009). The slope of dynamic gain in the neural arc transfer function from carotid sinus pressure to sympathetic nerve activity was not different between trials with and without the ADN stimulation (12.55 ± 0.93 vs. 13.03 ± 1.28 dB/decade in WKY, P = 0.542; and 17.37 ± 1.01 vs. 17.47 ± 1.64 dB/decade in SHR, P = 0.946). These results indicate that the tonic ADN stimulation does not significantly modify the dynamic characteristics of the carotid sinus baroreflex.

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Expression and localization of pannexin-1 and CALHM1 in porcine bladder and their involvement in modulating ATP release

ATP release from urinary bladder is vital for afferent signaling. The aims of this study were to localize calcium homeostasis modulator 1 (CALHM1) and pannexin-1 expression and to determine their involvement in mediating ATP release in the bladder. To determine gene expression and cellular distribution, PCR and immunohistochemistry were performed, respectively, in the porcine bladder. CALHM1 and pannexin-1-mediated ATP release in response to hypotonic solution (0.45% NaCl)-induced stretch, and extracellular Ca²⁺ depletion ([Ca²⁺]₀) was measured in isolated urothelial, suburothelial, and detrusor muscle cells. CALHM1 and pannexin-1 mRNA and immunoreactivity were detected in urothelial, suburothelial, and detrusor muscle layers, with the highest expression on urothelium. Hypotonic stretch caused a 2.7-fold rise in ATP release from all three cell populations (P < 0.01), which was significantly attenuated by the pannexin-1 inhibitor, ¹⁰Panx1, and by the CALHM1 antibody. Brefeldin A, a vesicular transport inhibitor, and ruthenium red, a nonselective CALHM1 channel blocker, also significantly inhibited stretch-mediated ATP release from urothelial cells. [Ca²⁺]₀ caused a marked, but transient, elevation of extracellular ATP level in all three cell populations. CALHM1 antibody and ruthenium red inhibited [Ca²⁺]₀-induced ATP release from urothelial cells, but their effects on suburothelial and detrusor cells were insignificant. ¹⁰Panx1 showed no significant inhibition of [Ca²⁺]₀-induced ATP release in any types of cells. The results presented here provide compelling evidence that pannexin-1 and CALHM1, which are densely expressed in the porcine bladder, function as ATP release channels in response to bladder distension. Modulation of extracellular Ca²⁺ may also regulate ATP release in the porcine bladder through voltage-gated CALHM1 ion channels.

http://ift.tt/2sbnqFT