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Background: A patient with chronic kidney disease and recurrent catheter-related thrombosis. Case presentation: The patient had femoral vein thrombosis and was scheduled for laparoscopically assisted continuous ambulatory peritoneal dialysis catheter insertion. The chief concerns during the perioperative period were the risk of pulmonary thromboembolism, limited venous access, and risk of bleeding as the patient was on anticoagulation therapy. Meticulous attention was paid to history, clinical examination, and to the ongoing treatment with regard to risk of systemic thrombosis. Conclusions: Management was tailored according to risk of thrombosis and bleeding during perioperative period along with identification adverse events associated with anticoagulation and preparedness for management of pulmonary embolism. [ABSTRACT FROM AUTHOR]

Objective: High burden of anaemia exists amongst rural adolescent girls in India. The objective of this study was to characterise anaemia in school going adolescent girls in rural Haryana, India. Design: Linear and multiple logistic regression analysis of data collected prior to an intervention trial was conducted. Participants were classified into anaemic (haemoglobin <12 g/dl) and non-anaemic group and were further classified into deficiencies of Fe, folate or vitamin B12, mixed, anaemia of other causes and inflammation. Setting: Three schools in Ballabgarh block of Faridabad District, Haryana, India. Participants: One hundered and ninety-eight non-anaemic and 202 anaemic adolescent girls (12–19 years). Results: Anaemic girls had 29·6 % Fe deficiency, 28·1 % folate or vitamin B12 deficiency, 15·8 % mixed deficiency and 9·7 % acute inflammation. Anaemia of other causes was found in 16·8 % of the anaemic participants. Girls with Fe and isolated folate deficiency had 2·5 times and four times higher odds of developing anaemia, respectively, as compared with non-anaemic girls. Fe deficiency with no anaemia was found amongst 11 % non-anaemic girls. Non-anaemic girls had a high prevalence of combined deficiency of folate or vitamin B12 (29·5 %) and acute inflammation (14·4 %). Conclusions: The current strategy of Fe and folic acid supplementation alone will not suffice for achieving the desired reduction in the prevalence of anaemia as unknown causes and anaemia of inflammation contribute to a substantial proportion of anaemia. Integrating other nutrition-specific components like improving water, sanitation and hygiene practices with the ongoing micronutrient supplementation program will comprehensively tackle anaemia. Unknown causes of anaemia warrant further research. [ABSTRACT FROM AUTHOR]

There are concerns that transcatheter or surgical aortic valve replacement (TAVR/SAVR) procedures are preferentially available to White patients. Our objective was to examine differences in utilization of aortic valve replacement and outcomes by race/ethnicity in the US for patients with aortic stenosis. We performed a serial cross-sectional cohort study of 299,976 Medicare beneficiaries hospitalized with principal diagnosis of aortic stenosis between 2012 and 2019 stratified by self-reported race/ethnicity (Black, Hispanic, Asian, Native American, and White). Outcomes included aortic valve replacement rates within 6 months of index hospitalization and associated procedural outcomes, including 30-day readmission, 30-day and 1-year mortality. Within 6 months of an index admission for aortic stenosis, 86.8% (122,457 SAVR; 138,026 TAVR) patients underwent aortic valve replacement. Overall, compared with White people, Black (HR 0.87 [0.85-0.89]), Hispanic (0.92 [0.88-0.96]), and Asian (0.95 [0.91-0.99]) people were less likely to receive aortic valve replacement. Among patients who were admitted emergently/urgently, White patients (41.1%, 95% CI, 40.7-41.4) had a significantly higher aortic valve replacement rate compared with Black (29.6%, 95% CI, 28.3-30.9), Hispanic (36.6%, 95% CI, 34.0-39.3), and Asian patients (35.4%, 95% CI, 32.3-38.9). Aortic valve replacement rates increased annually for all race/ethnicities. There were no significant differences in 30-day or 1-year mortality by race/ethnicity. Aortic valve replacement rates within 6 months of aortic stenosis admission are lower for Black, Hispanic, and Asian people compared to White people. These race-related differences in aortic stenosis treatment reflect complex issues in diagnosis and management, warranting a comprehensive reassessment of the entire care spectrum for disadvantaged populations. [ABSTRACT FROM AUTHOR]

Background: Malnutrition is associated with increased risk of morbidity and mortality amongst elderly population. Lack of scientific evidence exists on the status of malnutrition amongst elderly population residing at high altitude regions of Uttarakhand, India. Materials and methods: A community based cross-sectional study was conducted in high altitude regions of District Nainital. A total of 980 elderly subjects were selected from 30 clusters identified using population proportionate to size sampling method. Nutritional status of the elderly population was assessed using Mini Nutritional Assessment (MNA) tool. Data was entered in MS Excel 2007 and analyzed using SPSS version 20.0. Results: The results of MNA revealed that 14.3% of the elderly subjects were malnourished. High prevalence of malnutrition was found among subjects who were illiterate (74.5%), financially dependent (75.2%), belonged to low monthly income (43.3%) had poor appetite (71.6%) and chewing problems (63.1%); (p<0.0001). Conclusions: High prevalence of malnutrition was present amongst the elderly population in India. There is a need for timely assessment of malnutrition for maintenance of nutritional status and prevention of chronic diseases. [ABSTRACT FROM AUTHOR]

Background: Recent trends, including survival beyond 30 days, in aortic valve replacement (AVR) following the expansion of indications for transcatheter aortic valve replacement (TAVR) are not well-understood.Objectives: The authors sought to characterize the trends in characteristics and outcomes of patients undergoing AVR.Methods: The authors analyzed Medicare beneficiaries who underwent TAVR and SAVR in 2012 to 2019. They evaluated case volume, demographics, comorbidities, 1-year mortality, and discharge disposition. Cox proportional hazard models were used to assess the annual change in outcomes.Results: Per 100,000 beneficiary-years, AVR increased from 107 to 156, TAVR increased from 19 to 101, whereas SAVR declined from 88 to 54. The median [interquartile range] age remained similar from 77 [71-83] years to 78 [72-84] years for overall AVR, decreased from 84 [79-88] years to 81 [75-86] years for TAVR, and decreased from 76 [71-81] years to 72 [68-77] years for SAVR. For all AVR patients, the prevalence of comorbidities remained relatively stable. The 1-year mortality for all AVR decreased from 11.9% to 9.4%. Annual change in the adjusted odds of 1-year mortality was 0.93 (95% CI: 0.92-0.94) for TAVR and 0.98 (95% CI: 0.97-0.99) for SAVR, and 0.94 (95% CI: 0.93-0.95) for all AVR. Patients discharged to home after AVR increased from 24.2% to 54.7%, primarily driven by increasing home discharge after TAVR.Conclusions: The advent of TAVR has led to about a 60% increase in overall AVR in older adults. Improving outcomes in AVR as a whole following the advent of TAVR with increased access is a reassuring trend. [ABSTRACT FROM AUTHOR]

The limitations that hypoxia imparts on mitochondrial oxygen supply are circumvented by the activation of anaerobic metabolism and prosurvival mechanisms in hypoxia-tolerant animals. To deal with the hypoxia that jumbo squid (Dosidicus gigas) experience in the ocean’s depth, they depress their metabolic rate by up to 52% relative to normoxic conditions. This is coupled with molecular reorganization to facilitate their daily descents into the ocean’s oxygen minimum zone, where they face not only low oxygen levels but also higher pressures and colder frigid waters. Our current study explores the tissue-specific hypoxia responses of three central processes: (1) antioxidant enzymes responsible for defending against oxidative stress, (2) early apoptotic machinery that signals the activation of cell death, and (3) mitogen-activated protein kinases (MAPKs) that act as central regulators of numerouscellular processes. LuminexxMAP technology was used to assess protein levels and phosphorylation states under normoxic and hypoxic conditions in brains, branchial hearts, and mantle muscles. Hypoxic brains were found to activate apoptosis via up-regulation of phospho-p38, phospho-p53, activated caspase 8, and activated caspase 9, whereas branchial hearts were the only tissue to show an increase in antioxidant enzyme levels. Hypoxic muscles seemed the least affected by hypoxia. Our results suggest that hypoxic squid do not undergo large dynamic changes in the phosphorylation states of key apoptotic and central MAPK factors, except for brains, suggesting that these mechanisms are involved in squid hypometabolic responses. [ABSTRACT FROM AUTHOR]

• aPTT correlates poorly with anti-Xa in COVID-19 patients receiving unfractionated heparin. • aPTT potentially underestimates heparin activity compared with anti-Xa in COVID-19 patients receiving unfractionated heparin. • Elevated fibrinogen levels did not correlate with refractory aPTT in COVID-19 patients. [ABSTRACT FROM AUTHOR]

Background: Oldest-old patients (≥85 years) constitute half the acute myocardial infarction hospitalizations among older adults and more commonly have atypical presentation, under-treatment, and functional impairments. Yet this group has not been well characterized. We characterized differences in presentation, functional impairments, treatments, health status, and mortality among middle-old (75-84 years) and oldest-old patients with myocardial infarction.Methods: We analyzed data from the ComprehenSIVe Evaluation of Risk Factors in Older Patients with AMI (SILVER-AMI) study that enrolled 3041 patients ≥75 years of age from 94 hospitals across the US between 2013 and 2016. We performed Cox proportional hazards regression to examine the association between the oldest-old (n = 831) and middle-old (n = 2210) age categories with postdischarge 6-month case fatality rate adjusting for sociodemographic and clinical variables, and mobility impairment.Results: The oldest-old were less likely to present with chest pain (52.7% vs 57.7%) as their primary symptom or to receive coronary revascularization (58.1% vs 71.8) (P < .01 for both). The oldest-old were more likely to have functional impairments and had higher 6-month mortality compared with the middle-old patients (hazard ratio 1.78, 95% confidence interval, 1.39-2.28). This association was substantially attenuated after adjusting for mobility impairment (hazard ratio 1.29, confidence interval, 0.99-1.68).Conclusions: There is considerable heterogeneity in presentation, treatment, and outcomes among older patients with myocardial infarction. Mobility impairment, a marker for frailty, modifies the association between advanced age and treatments as well as outcomes. [ABSTRACT FROM AUTHOR]

The wood frog, Rana sylvatica, is the primary model animal used for studying vertebrate freeze tolerance. Freeze tolerance adaptations by wood frogs are mediated by a set of well-tuned regulatory controls at the molecular level, starting from cell signal transduction and gene expression events that are ultimately reflected in protective responses by multiple cell systems. Previous studies provided excellent presumptive evidence for the involvement of the NF-κB transcription factor in freeze tolerance. The present study of the NF-κB pathway focussed on freezing time points, 4 h frozen and 24 h frozen for liver and skeletal muscle in wood frog. The total protein levels of the major NF-κB subunits p50 and p65, its inhibitor, p-IκB, and downstream targets, ferritin heavy chain (FHC) and manganese superoxide dismutase (MnSOD) were quantified using western blots. Results showed a significant increase in the levels of NF-κB subunits and its downstream targets during freezing. Nuclear distributions of NF-κB subunits and transcript levels of FHC were analysed to delve deeper into the pathway. Results obtained from nuclear distribution analysis were consistent with the total protein levels showing increased levels of p50 and p65 during 24 h freezing conditions compared to controls but no change in phospho-p65 levels. Further, FHC transcript levels increased in 24 h frozen liver but did not change in frozen muscles. These findings suggest the activation of NF-κB antioxidant defenses in wood frogs during freezing in potential anticipation of high oxidative stress during reperfusion during thawing. [ABSTRACT FROM AUTHOR]

Introduction: The present study was conducted to assess the association of tobacco and alcohol consumption with cardiovascular risk factors among elderly population living at high altitude regions of India. Materials and Methods: A cross-sectional study was conducted among 1003 elderly people living in district Nainital, Uttarakhand state, India. Thirty subjects were identified from 30 villages using population proportionate to size sampling methodology. The data on the consumption of tobacco and alcohol, mini nutritional assessment, Barthel activities of daily living scale, height, weight, blood pressure, fasting blood sugar, triglycerides, and total cholesterol was collected. Results: We found that smoking tobacco was associated with high cholesterol, lower body mass index, and low nutritional status (all, P < 0.05). Elderly subjects who consumed alcohol had 1.56 times higher risk of having high fasting blood glucose. Conclusions: Consumption of tobacco and alcohol increased the risk of cardiovascular diseases among elderly subjects. There is a need to improve these modifiable health behaviors through targeted educational and rehabilitation programs. [ABSTRACT FROM AUTHOR]

Background and Aims: The aim of the study was to enumerate the sedative drugs used, assess the efficacy of sedative drugs, and determine the incidence of adverse events. Material and Methods: A prospective audit of children sedated for computerized tomography (CT) by anesthesiology team was conducted for a period of 4 months. The data included patient demographic variables, fasting period, medications administered, adequacy of sedation, imaging characteristics, adverse events, and requirement for escalated care. Results: A total of 331 children were enrolled for sedation by the anesthesia team. The drugs used for sedation were propofol, ketamine, and midazolam. Twenty-two percent children received one sedative drug, 60% children were administered two drugs, and 5% children required a combination of all three drugs for successful sedation. Sedation was effective for successful conduct of CT scan in 95.8% patients without the requirement of a repeat scan. Twelve (5%) children experienced adverse events during the study period. However, none of the adverse events necessitated prolonged postprocedural hospitalization or resulted in permanent neurologic injury or death. Conclusions: The current practice of sedation with propofol, ketamine, and midazolam, either single or in combination was efficacious in a high percentage of patients. The incidence of adverse events during the study period was low. [ABSTRACT FROM AUTHOR]

Introduction: Anemia is a major public health problem amongst elderly population in India. Anemia in old age further worsens the age-related decline in functional ability, mobility, fatigue, bone density, and skeletal muscle mass. There is lack of evidence on the prevalence and risk factors of anemia among elderly population. Hence, this study was undertaken. Methodology: A community-based cross-sectional study was conducted during the year 2015–2016 in District Nainital, Uttarakhand state, India. A total of 958 subjects were selected from 30 clusters (villages) identified using population proportional to size methodology. Information on sociodemographic profile, nutritional status, body mass index, and dietary intake was obtained. Blood sample was collected from each subject on the filter paper for estimation of hemoglobin (Hb) level using cyanmethemoglobin method. Results: We found that 92.1% of the elderly subjects were anemic. Moderate and severe anemia was found to be significantly higher among female subjects, unemployed, illiterates, subjects using smoke-producing fuel, subjects belonging to lower socioeconomic status, malnourished and underweight subjects, subjects with self-reported hyperacidity, and subjects who had not utilized health facility and had lower iron and vitamin C intake when compared with subjects with mild anemia and normal hemoglobin levels. Conclusion: High prevalence of anemia exists amongst elderly subjects living at high-altitude region of rural Uttarakhand State, India. There is a need to educate the elderly population about the importance of adequate intake of foods rich in iron and vitamin C to reduce the prevalence of anemia among them. [ABSTRACT FROM AUTHOR]

Characterisation of anaemia amongst school going adolescent girls in rural Haryana, India - CORRIGENDUM In the published article, the authors overlooked mentioning that 0.5g/dl was added to the original hemoglobin values to correct for the difference using direct and indirect cyanmethaemoglobin method. Characterisation of anaemia amongst school going adolescent girls in rural Haryana, India. [Extracted from the article]

Background: Poor dental health status has been suggested to negatively impact the food selection, ultimately leading to malnutrition. Objective: This study was undertaken to assess the association of dental health and nutritional status among elderly subjects in India. Methodology: A community-based cross-sectional study was conducted during 2015–2016 in district Nainital, Uttarakhand state, India. A total of 1003 elderly population were enrolled from 30 clusters (villages) identified using population proportionate to size sampling methodology. Information on sociodemographic profile and anthropometric measurements was collected. Body mass index (BMI) and Mini Nutritional Assessment scale (MNA) were calculated for assessment of nutritional status. A trained professional assessed the dental health status through physical examination. Dietary intake data was collected using 24-h dietary recall methodology. Results: We found that the prevalence of complete edentulism was 11%. Use of dentures was reported among only 9.6% subjects who were completely edentulous. Prevalence of underweight as defined by BMI and malnutrition as defined by MNA was higher among subjects with complete loss of teeth complete loss of teeth and chewing problems chewing problems and who did not wear dentures when compared with others. Subjects who wore dentures had significantly lower prevalence of malnutrition when compared with subjects who did not wear dentures. Conclusion: Dental health status was significantly associated with poor nutritional status among elderly subjects in India. There is a need for providing restorative dental healthcare services to elderly population to improve their nutritional status. [ABSTRACT FROM AUTHOR]

Objective: To assess the prevalence and risk factors of underweight, overweight and obesity among a geriatric population living in a high-altitude region of India.Design: Community-based cross-sectional study. Data were collected on sociodemographic profile and anthropometric parameters. Weight and height measurements were utilized for calculation of BMI. Nutrient intake data were collected using 24 h dietary recall.Setting: High-altitude region of Nainital District, Uttarakhand State, North India.Subjects: Community-dwelling geriatric subjects (n 981) aged 60 years or above.Results: We found that 26·6 % of the elderly subjects were underweight (BMI<18·5 kg/m2). Overweight (BMI 25·0-29·9 kg/m2) and obesity (BMI≥30·0 kg/m2) was seen among 18·0 % and 4·6 %, respectively. After controlling for potential cofounders, risk factors such as low level of education and income, chewing problems and lower number of daily meals were found to be associated with underweight. On the other hand, risk factors for overweight/obesity were lower age, high income and unskilled work.Conclusions: There is a need to develop and implement intervention strategies to prevent underweight, overweight and obesity among the geriatric population of India. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is a major contributing determinant in the development of ischemic heart diseases, stroke, and other vascular diseases. It increases the risk of mortality amongst the geriatric population. Aims & Objectives: To assess the prevalence of dyslipidemia in geriatric rural population residing in a hilly district of Uttarakhand state, India. Material & Methods: A community based cross-sectional study was conducted during 2015 - 2016 in District Nainital, Uttarakhand. A list of all villages with their population in the district was developed. From this list, thirty villages were identified using population proportionate to size sampling method. From each village 30 geriatric subjects were selected. A total of 1003 geriatric subjects aged 60 years and above were included in the study. The data was collected on socio demographic profile and lipid profile from all the enrolled subjects. The prevalence of dyslipidemia was assessed using National Cholesterol Education Programme (NCEP) criteria. Result: The overall prevalence of dyslipidemia was 50.6%. A total of 26.3% participants had hypercholesterolemia, 34.2% had hypertriglyceridemia and 23.5% had high LDL levels. The prevalence of dyslipidemia was higher in women compared to men. Conclusion: High prevalence of dyslipidemia was found amongst geriatric rural population. [ABSTRACT FROM AUTHOR]

A WHO guideline is any document containing recommendations about health interventions, whether these are clinical, public health or policy recommendations. A recommendation provides information about what policymakers, health-care providers or patients should do. It implies a choice between different interventions that have an impact on health and that have implications for the use of resources. The purpose of WHO guidelines is to improve the health and well-being of individuals and populations To accomplish that, WHO guidelines need to be formulated, disseminated, adopted or adapted, and their recommendations implemented. Recommendations in WHO guidelines are based on a systematic review of the scientific literature guided by specific key questions about the intervention, exposure or approach under consideration. The science underpinning evidence identification and synthesis and the translation of a body of evidence into recommendations continues to evolve. Because of this, any manual on how to produce a guideline requires frequent reassessment and updating. [ABSTRACT FROM AUTHOR]

Lipids are complex organic molecules that fulfill energy demands and sometimes act as signaling molecules. They are mostly found in membranes, thus playing an important role in membrane trafficking and protecting the cell from external dangers. Based on the composition of the lipids, their fluidity and charge, their interaction with embedded proteins vary greatly. Bacteria can hijack host lipids to satisfy their energy needs or to conceal themselves from host cells. Intracellular bacteria continuously exploit host, from their entry into host cells utilizing host lipid machinery to exiting through the cells. This acquisition of lipids from host cells helps in their disguise mechanism. The current review explores various mechanisms employed by the intracellular bacteria to manipulate and acquire host lipids. It discusses their role in manipulating host membranes and the subsequence impact on the host cells. Modulating these lipids in macrophages not only serve the purpose of the pathogen but also modulates the macrophage energy metabolism and functional state. Additionally, we have explored the intricate pathogenic relationship and the potential prospects of using this knowledge in lipid-based therapeutics to disrupt pathogen dominance. [ABSTRACT FROM AUTHOR]

Background/Objectives Although skin disease and skin cancers cause significant morbidity and mortality in Australia, limited time is dedicated to dermatology teaching in most medical courses. The aim of this study was to define the current state of dermatology teaching in Australian medical schools with a view to developing a national core curriculum for dermatology. Methods An electronic questionnaire was circulated to the dermatology teaching leads and relevant medical program coordinators of the 18 medical schools in Australia. Results Replies were received from 17 medical schools. Dermatology was included as part of the core curriculum in 15 schools. Time set aside for dermatology teaching varied, as reflected by the number of lectures delivered (0-21, mean 5, median 3) and minimum clinics attended (0-10, mean 1.2, median 0). Only four medical schools had a compulsory clinical attachment in dermatology. Furthermore, satisfying requirements in dermatology was mentioned in the university examination regulations in only six schools. Certain core learning outcomes were addressed in most schools, including the structure and function of the skin, common conditions such as atopic dermatitis and psoriasis and cutaneous malignancies. However, there were important omissions, ranging from common problems like dermatophyte infections and drug reactions to the recognition of dermatological emergencies. Conclusions These results are a compelling impetus to improve current standards of dermatology teaching, learning and assessment. The introduction of a national core curriculum would provide guidelines for dermatology teaching in medical schools, enabling the more effective utilisation of available time for key learning outcomes. [ABSTRACT FROM AUTHOR]

Background: National Family Health Survey (NFHS) documented that nearly 5.8 million children (6.4%) are undernourished in India which is l/3rd of the world's share. Objective: i) To assess the concomitant prevalence of severe wasting, severe stunting and severe underweight among children 6-59 months in a rural population of Northern India. Methods: A cross-sectional study was conducted in 2 blocks of district Meerut, Uttar Pradesh during 2013-2015. A total of 70 villages were included and all children in the age group of 6-59 months were covered by house to house visits. Data on socio-demographic profile and anthropometry was collected utilizing standards methods and equipment's. The Z-scores for weight-for-height (WFH), height-for-age (HFA), and weight-for-age (WFA) were calculated using WHO child growth standards. Results: A total of 19449 children in the age group of 6-59 months from house to house survey were approached. Out of 19449 children, 464 children were excluded due to erroneous age estimation; knock knees; physically handicapped and spinal deformities. Thus, 18985 children were enrolled for the present study. The weight, height and age were available for 18474, 18595 and 18983 children. The prevalence of severe wasting, severe stunting and severe underweight was found to be 2.2%, 16.2% and 12.2%, respectively. Concomitant presence of severe wasting, severe stunting and severe underweight was found in 0.9% (171/18,463) children. Conclusion: High prevalence of severe wasting, severe stunting and severe underweight was found in children from district Meerut indicating poor nutritional status. [ABSTRACT FROM AUTHOR]

Background: Optimal infant and young child feeding (IYCF) practices during first 2 years of life is the key to ensuring optimal growth and development of the infant. Improving IYCF practices have an important role in reducing morbidity and mortality amongst under 5 children in India. Material & Methods: The secondary data from National Family Health Survey (NFHS)-3 and NFHS-4 was analyzed. Objective: To assess the trend in IYCF practices during 2005 -- 2015 for 13 selected states of India. Results: It was found that over a decade, there has been an improvement in early initiation of breast feeding and exclusive breastfeeding for 6 months amongst infant in 11 out of 13 states. However, a reduction in the timely initiation of complementary feeding amongst children in the age group of 6-8 months has been observed in 9 out of 13 states. Conclusion: There is a need to strengthen the efforts to further improve the IYCF practices in India for reducing high rates of undernutrition in the country. [ABSTRACT FROM AUTHOR]

Perineural invasion ( PNI) occurring in non-melanoma skin cancers ( NMSC) is associated with an increased risk of locoregional recurrence and reduced disease-free survival. This necessitates early and accurate diagnosis, appropriate risk-stratification and a clear management strategy. The diagnosis of PNI is based on careful clinical assessment, imaging and histopathology. Surgery, preferably with margin control, and definitive or adjuvant radiotherapy ( ART) are established treatment strategies for PNI. Clinical uncertainty remains over the role of ART in incidental PNI. This review synthesises current literature to ascertain which clinicopathological features impart a higher risk to individuals with PNI in NMSC, in order to provide treatment algorithms, including the identification of patient subsets that are most likely to benefit from ART. This includes those with extratumoural PNI, involvement of larger-calibre nerves, tumour invasion beyond dermis, recurrent tumour or diffuse intratumoural spread. Patients with clinical PNI may be optimally managed by a multidisciplinary head and neck cancer service that is best placed to offer skull base surgery and intensity-modulated radiation therapy ( IMRT). The management options presented are stratified by histological subtype and a new classification of PNI into low-risk, medium-risk and high-risk groups. [ABSTRACT FROM AUTHOR]

Excess dosing of anticoagulant agents has been linked to increased risk of bleeding after percutaneous coronary intervention (PCI) for women compared with men, but these studies have largely included older patients. We sought to determine the prevalence and gender-based differences of excess dosing of anticoagulants including glycoprotein IIb/IIIa inhibitors, bivalirudin, and unfractionated heparin in young patients with acute myocardial infarction who underwent PCI and to examine its association with bleeding. Of 2,076 patients enrolled in the Variation in Recovery: Role of Gender on Outcomes of Young Acute Myocardial Infarction Patients study who underwent PCI, we abstracted doses of unfractionated heparin, bivalirudin, and glycoprotein IIb/IIIa inhibitors administered during PCI from the medical records. At least 47.2% received at least 1 excess dose of an anticoagulant, which did not differ by gender. We used logistic regression to determine the predictors of excess dosing and the association of excess dosing with bleeding. In multivariable analysis, only lower body weight and younger age were significant predictors of excess dosing. Bleeding was higher in young women who received excess dosing versus those who did not (9.3% vs 6.0%, p = 0.03) but was comparable among men (5.2% vs 5.9%, p = 0.69) in univariate analysis. In multivariable analysis, there was a trend to an association between excess dosing and bleeding (odds ratio 1.33, 95% confidence interval 0.92 to 1.91) although not statistically significant. In conclusion, approximately half of the patients received excess dosing of anticoagulant drugs during PCI, which did not vary based on gender. There was a trend toward an association between excess dosing and increased bleeding, although not statistically significant. [ABSTRACT FROM AUTHOR]

Wood frogs (Rana sylvatica) experience months of whole-body freezing during winter. Anoxia is one of the side stresses along with cell dehydration and hyperglycemia. Among multicellular organisms, communication and coordination is essential between neighbouring cells, particularly under stress conditions. Notch signaling is an effective communication channel between cells and regulates multiple pro-survival pathways. Signaling initiates when membrane-bound ligands Delta-like (DLL) or Jagged (JAG) interact with notch receptors. Activated receptor undergoes cleavage to release intracellular domain (NICD) in the cytoplasm. NICD translocates to the nucleus and forms a transcriptional complex with MAML and RBPJ that interacts with promoter regions and activates stress-specific genes. The role of notch signaling in enduring anoxia was assessed by studying the pathway components using immunoblots, TF-ELISA, and qPCR on treated samples of liver and heart. Bioinformatics tool Pymol was used to prepare structures based on available protein sequences for ligands, NOTCH receptor and the transcriptional complex. The results showed an increase in the levels of both ligands and receptors but decreased levels of RBPJ, suggesting an effective transmission of stress signal but suppressed gene transcription that goes in accordance with lowering energy expense required in energy crisis during anoxia. The study suggests Notch-independent activation of HES1 and HES5. Tissue-specific response of HES1, HES5, and MAML implies energy conservation and myocardial protection. The current study is the first analysis of the regulation of notch signaling in amphibians on encountering anoxic conditions that present multiple future directions. [Display omitted] • Notch1 and Notch2 represent stress specific role in anoxia/recovery. • DLL4-NOTCH1 signaling provides immune response in liver via macrophage activation. • Decreased levels of RBPJ suggest suppressed gene transcription to lower energy expense. • MAML and HES5 shows "functional switching" to activate MyoD for myocardial protection. • HES1 controls glucocorticoid regulated carbohydrate metabolism to conserve energy. [ABSTRACT FROM AUTHOR]

Background: Various national campaigns launched in recent years have focused on young women with acute myocardial infarctions (AMIs). Contemporary longitudinal data about sex differences in clinical characteristics, hospitalization rates, length of stay (LOS), and mortality have not been examined. Objectives: This study sought to determine sex differences in clinical characteristics, hospitalization rates, LOS, and in-hospital mortality by age group and race among young patients with AMIs using a large national dataset of  U.S. hospital discharges. Methods: Using the National Inpatient Sample, clinical characteristics, AMI hospitalization rates, LOS, and in-hospital mortality were compared for patients with AMI across ages 30 to 54 years, dividing them into 5-year subgroups from 2001 to 2010, using survey data analysis techniques. Results: A total of 230,684 hospitalizations were identified with principal discharge diagnoses of AMI in 30- to 54-year-old patients from Nationwide Inpatient Sample data, representing an estimated 1,129,949 hospitalizations in the United States from 2001 to 2010. No statistically significant declines in AMI hospitalization rates were observed in the age groups >55 years or stratified by sex. Prevalence of comorbidities was higher in women and increased among both sexes through the study period. Women had longer LOS and higher in-hospital mortality than men across all age groups. However, observed in-hospital mortality declined significantly for women from 2001 to 2010 (from 3.3% to 2.3%, relative change 30.5%; p for trend < 0.0001) but not for men (from 2% to 1.8%, relative change 8.6%; p for trend = 0.60). Conclusions: AMI hospitalization rates for young people have not declined over the past decade. Young women with AMIs have more comorbidity, longer LOS, and higher in-hospital mortality than young men, although their mortality rates are decreasing. [ABSTRACT FROM AUTHOR]

Mucormycosis, although said to be less common than candidiasis and aspergillosis is becoming increasingly associated with many co-morbid conditions and immunosuppression. Renal involvement, rarely reported previously, has also been documented with increasing frequency in recent times in both diseased as well as apparently healthy individuals. The kidneys may be involved in disseminated disease or have an isolated involvement for unexplained reasons. The manifestations are very serious particularly in patients with bilateral renal mucormycosis who often develop acute kidney injury and usually have a fatal outcome. The diagnosis of the renal mucormycosis is based on renal histology sections of renal biopsy or nephrectomised kidneys. Imaging with computerised tomography with contrast is of tremendous help in early identification of these cases before histological diagnosis. Once diagnosis is established, prompt treatment with antifungal medication, including Amphotericin-B (and its lipid formulations) and posaconazole, and removal of infected tissue is necessary to save from otherwise fatal infection. [ABSTRACT FROM AUTHOR]

Rana sylvatica (also known as Boreorana sylvatica) is one of the few vertebrates that spend extreme winters showing no physiological signs of life. Up to 70% of the total body water of the wood frog freezes as extracellular ice. Survival in extreme conditions requires regulation at transcriptional and translational levels to activate prosurvival pathways. N6-methyladenosine (m6A) methylation is one of the most common RNA modifications, regulating transcript processing and translation by executing important functions that affect regulatory pathways in stress conditions. In the study, regulation of m6A-related proteins in the liver of R. sylvatica was analyzed during 24 h frozen and 8 h thaw conditions. Decreases in the activity of demethylases of 28.44 ± 0.4% and 24.1 ± 0.9% of control values in frozen and thaw tissues, respectively, were observed. Total protein levels of m6A methyltransferase complex components methyltransferase-like 14 and Wilm's tumor associated protein were increased by 1.28-fold and 1.42-fold, respectively, during freezing. Demethylase fat mass and obesity, however, showed a decreasing trend, with a significant decrease in abundance during recovery from frozen conditions. Levels of mRNA degraders YTHDF2 and YTHDC2 also decreased under stress. Overall, increased levels of m6A methylation complex components, and suppressed levels of readers/erasers, provide evidence for the potential role of RNA methylation in freezing survival and its regulation in a hypometabolic state. [ABSTRACT FROM AUTHOR]

Wood frogs (Rana sylvatica) display well-developed anoxia tolerance as one component of their capacity to endure prolonged whole-body freezing during the winter months. Under anoxic conditions, multiple cellular responses are triggered to efficiently cope with stress by suppressing gene transcription and promoting activation of mechanisms that support cell survival. Activation of the Hippo signaling pathway initiates a cascade of protein kinase reactions that end with phosphorylation of YAP protein. Multiple pathway components of the Hippo pathway were analyzed via immunoblotting, qPCR or DNA-binding ELISAs to assess the effects of 24 h anoxia and 4 h aerobic recovery, compared with controls, on liver and heart metabolism of wood frogs. Immunoblot results showed significant increases in the relative levels of multiple proteins of the Hippo pathway representing an overall activation of the pathway in both organs under anoxia stress. Upregulation of transcript levels further confirmed this. A decrease in YAP and TEAD protein levels in the nuclear fraction also indicated reduced translocation of these proteins. Decreased DNA-binding activity of TEAD at the promoter region also suggested repression of gene transcription of its downstream targets such as SOX2 and OCT4. Furthermore, changes in the protein levels of two downstream targets of TEAD, OCT4 and SOX2, established regulated transcriptional activity and could possibly be associated with the activation of the Hippo pathway. Increased levels of TAZ in anoxic hearts also suggested its involvement in the repair mechanism for damage caused to cardiac muscles during anoxia. In summary, this study provides the first insights into the role of the Hippo pathway in maintaining cellular homeostasis in response to anoxia in amphibians. [ABSTRACT FROM AUTHOR]

The red-eared slider (Trachemys scripta elegans) undergoes numerous changes to its physiological and metabolic processes to survive without oxygen. During anoxic conditions, its metabolic rate drops drastically to minimize energy requirements. The alterations in the central metabolic pathways are often accomplished by the regulation of key enzymes. The regulation of one such enzyme, fructose-1,6-bisphosphatase (FBPase; EC 3.1.3.11), was characterized in the present study during anoxia in liver. FBPase is a crucial enzyme of gluconeogenesis. The FBPase was purified from liver tissue in both control and anoxic conditions and subsequently assayed to determine the kinetic parameters of the enzyme. The study revealed the relative degree of post-translational modifications in the FBPase from control and anoxic turtles. Further, this study demonstrated a significant decrease in the maximal activity in anoxic FBPase and decreased sensitivity to its substrate Fructose-1,6-bisphosphate (FBP) when compared to the control. Immunoblotting demonstrated increased threonine phosphorylation (~1.4-fold) in the anoxic FBPase. Taken together, these results suggest that the phosphorylation of liver FBPase is an important step in suppressing FBPase activity, ultimately leading to the inhibition of gluconeogenesis in the liver of the red-eared slider during anaerobic conditions. [ABSTRACT FROM AUTHOR]

• JMJDs regulate gene transcription to reprioritize pro-survival pathways. • JMJD targets include antioxidation and cellular repair genes under MRD. • Changes in total protein levels of AHCY and MAT maintain cellular SAM/SAH ratio. • Increased GSH concentration provide antioxidant protection during anoxia in liver. • Regulation of myod with increased levels of JMJD2C and H3K9Me2 in anoxic muscle. Wood frogs (Rana sylvatica) can survive extended periods of whole body freezing. Freezing imparts multiple stresses on cells that include anoxia and dehydration, but these can also be experienced as independent stresses. Under anoxia stress, energy metabolism is suppressed, and pro-survival pathways are prioritized to differentially regulate some transcription factors including OCT1 and OCT4. Jumonji C domain proteins (JMJD1A and JMJD2C) are hypoxia responsive demethylases whose expression is accelerated by OCT1 and OCT4 which act to demethylate genes related to the methionine cycle. The responses by these factors to 24 h anoxia exposure and 4 h aerobic recovery was analyzed in liver and skeletal muscle of wood frogs to assess their involvement in metabolic adaptation to oxygen limitation. Immunoblot results showed a decrease in JMJD1A levels under anoxia in liver and muscle, but an increase was observed in JMJD2C demethylase protein in anoxic skeletal muscle. Protein levels of adenosylhomocysteinase (AHCY) and methionine adenosyl transferase (MAT), enzymes of the methionine cycle, also showed an increase in the reoxygenated liver, whereas the levels decreased in muscle. A transcription factor ELISA showed a decrease in DNA binding by OCT1 in the reoxygenated liver and anoxic skeletal muscle, and transcript levels also showed tissue specific gene expression. The present study provides the first analysis of the role of the OCT1 transcription factor, associated proteins, and lysine demethylases in mediating responses to anoxia by wood frog tissues. [ABSTRACT FROM AUTHOR]

Dowling- Degos disease ( DDD) is a rare inherited pigmentary disorder characterised by reticulate pigmentation at flexural sites. No treatment modality has yet been established as a definitive method for the effective elimination of lentigines in DDD. We present a case of a 24-year old woman with DDD treated successfully using intense pulsed light as a novel management strategy. [ABSTRACT FROM AUTHOR]

Wood frogs (Rana sylvatica) can survive seasonal exposure to subzero temperatures. During freeze/thaw, the frogs confront oxidative stress due to concurrent stress conditions of anoxia, ischemia and dehydration. Wood frogs also need to cope with additional oxidative stress associated with hyperglycemia due to accumulation of the cryoprotectant glucose. Here we explore the transcription factor Nrf2 (nuclear factor erythroid 2 related factor 2) and Nrf2 related antioxidant enzymes in liver and skeletal muscle of wood frogs undergoing freeze/thaw and glucose injection. Nrf2 binding activity to DNA was assessed and GSK3β, an upstream regulator of Nrf2, and gsta1 , a downstream gene under Nrf2 control, were also evaluated. A multiplex protein assay was used to analyze multiple Nrf2 related antioxidant enzymes. Elevated DNA binding activity was observed in frozen frogs as compared to unfrozen controls for both liver and skeletal muscle. Interestingly, high glucose also enhanced binding to the ARE (antioxidant response element) in vitro in unfrozen frogs for both tissues. However, high blood glucose concentration failed to stimulate Nrf2 dependent gsta1 gene expression in glucose loaded frogs, although this was observed in liver of frozen frogs. A multiplex protein assay revealed that Prdx2 responded robustly in both tissues, decreasing in liver but rising in muscle. Glucose loaded frogs showed tissue specific suppression of catalase, Prdx2 (Peroxiredoxin-2) and SOD2 (superoxide dismutase 2) in liver and of Prdx2 alone in muscle. Our study further extended our understanding of the roles of Nrf2 dependent antioxidant defenses in wood frog freezing survival. [Display omitted] • Wood frogs likely regulate liver and skeletal muscle Nrf2 via the AKT-GSK3β pathway upon stress exposure/glucose loading. • Freezing stress adaptations beyond high glucose content likely required for Nrf2 activation in both wood frog tissues. • Tissue specific protein regulations on Nrf2 linked antioxidant enzymes were observed upon stress exposure/glucose loading. [ABSTRACT FROM AUTHOR]

Respiratory syncytial virus (RSV) is commonly known to cause an influenza-like illness. However, it can also cause more severe disease in young children and older adults comprising of organ transplant patients with immunocompromised status. Till date, only four cases of RSV infections have been reported in HIV-positive adults. We describe here a case of HIV-positive female with relatively preserved immune function who presented with RSV infection requiring ventilation and showed improvement after prompt treatment with intravenous immunoglobulin. [ABSTRACT FROM AUTHOR]

The wood frog (Rana sylvatica) is a remarkable species. These frogs can endure prolonged oxygen deprivation as well as dehydration to ~60% of total body water lost and, combining these two abilities, they survive whole body freezing for weeks at a time during the winter. Episodes of anoxia/reoxygenation or freeze/thaw can trigger elevated production of reactive oxygen species (ROS) causing cellular damage, especially when oxygen is reintroduced during reoxygenation or thawing. To mitigate ROS damage, stress-responsive transcription factors such as the Octamer Binding Transcription factor (OCT4) and Nuclear factor (erythroid-derived 2)-like 2 transcription factor (Nrf2) were postulated to be involved in enhancing pro-survival pathways and antioxidant defenses. The present study used immunoblotting to analyze OCT4 and Nrf2 responses (and downstream factors under their control) to 24 h anoxia and 4 h reoxygenation in liver and skeletal muscle of wood frogs, with an emphasis on antioxidant systems. Surprisingly, no change was observed in relative total protein expression of either of the two transcription factors in liver. Furthermore, a significant decrease in total protein levels of OCT4 and Nrf2 occurred in skeletal muscle after 4 h recovery. However, essential cofactors of OCT4 and Nrf2 were significantly upregulated during anoxia and/or recovery. Downstream targets of the Nrf2-ARE pathway were evaluated, including glutathione- S -transferases (GSTs) and aldo-keto reductases (AKRs). Significant increases in GSTT1 and GSTP1 were observed in liver and muscle whereas AKRs showed a tissue specific response to both anoxia and recovery from anoxia. This study demonstrates activation of antioxidants as a cell protective mechanism against generation of reactive oxygen species during anoxia in wood frogs. Unlabelled Image • Antioxidant defense response gets activated in response to anoxia in wood frogs. • Upregulation of Glutathione S Transferases (GST) T1 and GSTP1 were observed in anoxia. • Aldo Keto Reductases show a tissue specific regulation in response to oxidative stress. [ABSTRACT FROM AUTHOR]

Orthotopic transcatheter tricuspid valve replacement (TTVR) devices have been shown to be highly effective in reducing tricuspid regurgitation (TR), and interest in this therapy is growing with the recent commercial approval of the first orthotopic TTVR. Recent TTVR studies report preexisting cardiac implantable electronic device (CIED) transvalvular leads in ∼35% of patients, with entrapment during valve implantation. Concerns have been raised regarding the safety of entrapping leads and counterbalanced against the risks of transvenous lead extraction (TLE) when indicated. This Heart Valve Collaboratory consensus document attempts to define the patient population with CIED lead-associated or lead-induced TR, describe the risks of lead entrapment during TTVR, delineate the risks and benefits of TLE in this setting, and develop a management algorithm for patients considered for TTVR. An electrophysiologist experienced in CIED management should be part of the multidisciplinary heart team and involved in shared decision making. [Display omitted] • Implanted CIED leads in patients with severe TR face risks of entrapment or complications of extraction. • An MDT, including electrophysiologists experienced in managing CIEDs, should collaborate in decision making for patients with severe TR before TTVR. • Higher quality evidence is needed to better inform estimates of the risks of entrapment and potential risks and benefits of CIED lead extraction in patients with severe TR who are undergoing transcatheter intervention. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Effectiveness and Feasibility of Weekly Iron and Folic Acid Supplementation to Adolescent Girls and Boys through Peer Educators at Community Level in the Tribal Area of Gujarat" by Shobha P. Shah et al. in the February 26, 2016 issue.

The article presents a procedure, left subclavian vein was cannulated uneventfully using bony landmark technique done on a 52 year old male for hyperalimentation and administration of inotropes and intravascular fluids in Intensive Care Unit. Topics discussed other procedures done on the patient and post-insertion chest radiograph revealed the position of the catheter in the left para mediastinal location which raised suspicion of a left-sided superior location vena cava.