Thyroid dysfunction among Indian pregnant women and its effect on the maternal and fetal outcome

Background: Screening of thyroid disorders in antenatal women during first trimester, to recommend management of thyroid disorder during pregnancy and to know the maternal and fetal outcome of such pregnancy.Methods: This is a prospective study for the incidence of thyroid disorder in early pregnancy and the outcome of such pregnancy. 100 cases were randomly selected from the antenatal clinic at a tertiary care hospital in India and after fulfilling the inclusion criteria they were subjected to screening for thyroid disorder till 13 weeks of pregnancy. TSH is often considered the “gold standard” for assessing thyroid function. If the participant had normal value then she was not subjected to follow up, but if abnormal, then follow up was done after 4-8 weeks, thyroid profile was repeated and if values were altered, they were medically managed and closely monitored. The obstetric and perinatal outcome of the pregnancy was noted.Results: In this screening study to detect and manage thyroid disorder, 100 antenatal women were selected randomly, from which 49 women where primigravidae and 51 women were multi-gravidae, 17 of them were of <20years, 54 were between 21 to 25 years. There was 5 percent incidence of thyroid disorder in the study group. There were 3 cases of hyperthyroidism and 2 cases of overt hypothyroidism which had poor fetal and maternal outcome on follow up.Conclusions: Our study shows that the evaluation of thyroid disorders in early pregnancy and timely intervention will lead to a decrease in the complications thereby improving the maternal and fetal outcome

Semantic Video Segmentation for Intracytoplasmic Sperm Injection Procedures

We present the first deep learning model for the analysis of intracytoplasmic sperm injection (ICSI) procedures. Using a dataset of ICSI procedure videos, we train a deep neural network to segment key objects in the videos achieving a mean IoU of 0.962, and to localize the needle tip achieving a mean pixel error of 3.793 pixels at 14 FPS on a single GPU. We further analyze the variation between the dataset's human annotators and find the model's performance to be comparable to human experts.Comment: Accepted at the 'Medical Imaging meets NeurIPS Workshop' at the 34th Conference on Neural Information Processing System

Gender differences in outcomes of patients with cystic fibrosis

Background: Cystic fibrosis (CF) is a common life-shortening genetic disease in which women have been described to have worse outcomes than males, particularly in response to respiratory infections with Pseudomonas aeruginosa. However, as advancements in therapies have improved life expectancy, this gender disparity has been challenged. The objective of this study is to examine whether a gender-based survival difference still exists in this population and determine the impact of common CF respiratory infections on outcomes in males versus females with CF. Methods: We conducted a retrospective cohort analysis of 32,766 patients from the United States Cystic Fibrosis Foundation Patient Registry over a 13-year period. Kaplan-Meier and Cox proportional hazards models were used to compare overall mortality and pathogen based survival rates in males and females. Results: Females demonstrated a decreased median life expectancy (36.0 years; 95% confidence interval [CI] 35.0–37.3) compared with men (38.7 years; 95% CI 37.8–39.6; p<0.001). Female gender proved to be a significant risk factor for death (hazard ratio 2.22, 95% CI 1.79–2.77), despite accounting for variables known to influence CF mortality. Women were also found to become colonized earlier with several bacteria and to have worse outcomes with common CF pathogens. Conclusions: CF women continue to have a shortened life expectancy relative to men despite accounting for key CF-related comorbidities. Women also become colonized with certain common CF pathogens earlier than men and show a decreased life expectancy in the setting of respiratory infections. Explanations for this gender disparity are only beginning to be unraveled and further investigation into mechanisms is needed to help develop therapies that may narrow this gender gap

17β-Estradiol dysregulates innate immune responses to Pseudomonas aeruginosa respiratory infection and is modulated by estrogen receptor antagonism

ABSTRACT Females have a more severe clinical course than males in terms of several inflammatory lung conditions. Notably, females with cystic fibrosis (CF) suffer worse outcomes, particularly in the setting of Pseudomonas aeruginosa infection. Sex hormones have been implicated in experimental and clinical studies; however, immune mechanisms responsible for this sex-based disparity are unknown and the specific sex hormone target for therapeutic manipulation has not been identified. The objective of this study was to assess mechanisms behind the impact of female sex hormones on host immune responses to P. aeruginosa . We used wild-type and CF mice, which we hormone manipulated, inoculated with P. aeruginosa , and then examined for outcomes and inflammatory responses. Neutrophils isolated from mice and human subjects were tested for responses to P. aeruginosa . We found that female mice inoculated with P. aeruginosa died earlier and showed slower bacterial clearance than males ( P &lt; 0.0001). Ovariectomized females supplemented with 17β-estradiol succumbed to P. aeruginosa challenge earlier than progesterone- or vehicle-supplemented mice ( P = 0.0003). 17β-Estradiol-treated ovariectomized female mice demonstrated increased lung levels of inflammatory cytokines, and when rendered neutropenic the mortality difference was abrogated. Neutrophils treated with 17β-estradiol demonstrated an enhanced oxidative burst but decreased P. aeruginosa killing and earlier cell necrosis. The estrogen receptor (ER) antagonist ICI 182,780 improved survival in female mice infected with P. aeruginosa and restored neutrophil function. We concluded that ER antagonism rescues estrogen-mediated neutrophil dysfunction and improves survival in response to P. aeruginosa . ER-mediated processes may explain the sex-based mortality gap in CF and other inflammatory lung illnesses, and the ER blockade represents a rational therapeutic strategy. </jats:p

Degradation of arouser by endosomal microautophagy is essential for adaptation to starvation in Drosophila

Hunger drives food-seeking behaviour and controls adaptation of organisms to nutrient availability and energy stores. Lipids constitute an essential source of energy in the cell that can be mobilised during fasting by autophagy. Selective degradation of proteins by autophagy is made possible essentially by the presence of LIR and KFERQ-like motifs. Using in silico screening of Drosophila proteins that contain KFERQ-like motifs, we identified and characterized the adaptor protein Arouser, which functions to regulate fat storage and mobilisation and is essential during periods of food deprivation. We show that hypomorphic arouser mutants are not satiated, are more sensitive to food deprivation, and are more aggressive, suggesting an essential role for Arouser in the coordination of metabolism and food-related behaviour. Our analysis shows that Arouser functions in the fat body through nutrient-related signalling pathways and is degraded by endosomal microautophagy. Arouser degradation occurs during feeding conditions, whereas its stabilisation during non-feeding periods is essential for resistance to starvation and survival. In summary, our data describe a novel role for endosomal microautophagy in energy homeostasis, by the degradation of the signalling regulatory protein Arouser

Sirtuin 6 inhibition protects against glucocorticoid-induced skeletal muscle atrophy by regulating IGF/PI3K/AKT signaling

Chronic activation of stress hormones such as glucocorticoids leads to skeletal muscle wasting in mammals. However, the molecular events that mediate glucocorticoid-induced muscle wasting are not well understood. Here, we show that SIRT6, a chromatin-associated deacetylase indirectly regulates glucocorticoid-induced muscle wasting by modulating IGF/PI3K/AKT signaling. Our results show that SIRT6 levels are increased during glucocorticoid-induced reduction of myotube size and during skeletal muscle atrophy in mice. Notably, overexpression of SIRT6 spontaneously decreases the size of primary myotubes in a cell-autonomous manner. On the other hand, SIRT6 depletion increases the diameter of myotubes and protects them against glucocorticoid-induced reduction in myotube size, which is associated with enhanced protein synthesis and repression of atrogenes. In line with this, we find that muscle-specific SIRT6 deficient mice are resistant to glucocorticoid-induced muscle wasting. Mechanistically, we find that SIRT6 deficiency hyperactivates IGF/PI3K/AKT signaling through c-Jun transcription factor-mediated increase in IGF2 expression. The increased activation, in turn, leads to nuclear exclusion and transcriptional repression of the FoxO transcription factor, a key activator of muscle atrophy. Further, we find that pharmacological inhibition of SIRT6 protects against glucocorticoid-induced muscle wasting in mice by regulating IGF/PI3K/AKT signaling implicating the role of SIRT6 in glucocorticoid-induced muscle atrophy.Fil: Mishra, Sneha. No especifíca;Fil: Cosentino, Claudia. Harvard Medical School; Estados UnidosFil: Tamta, Ankit Kumar. No especifíca;Fil: Khan, Danish. No especifíca;Fil: Srinivasan, Shalini. No especifíca;Fil: Ravi, Venkatraman. No especifíca;Fil: Abbotto, Elena. Università degli Studi di Genova; ItaliaFil: Arathi, Bangalore Prabhashankar. No especifíca;Fil: Kumar, Shweta. No especifíca;Fil: Jain, Aditi. No especifíca;Fil: Ramaian, Anand S.. No especifíca;Fil: Kizkekra, Shruti M.. No especifíca;Fil: Rajagopal, Raksha. No especifíca;Fil: Rao, Swathi. No especifíca;Fil: Krishna, Swati. No especifíca;Fil: Asirvatham Jeyaraj, Ninitha. Indian Institute of Technology; IndiaFil: Haggerty, Elizabeth R.. Harvard Medical School; Estados UnidosFil: Silberman, Dafne Magalí. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Centro de Estudios Farmacológicos y Botánicos. Universidad de Buenos Aires. Facultad de Medicina. Centro de Estudios Farmacológicos y Botánicos; ArgentinaFil: Kurland, Irwin J.. No especifíca;Fil: Veeranna, Ravindra P.. No especifíca;Fil: Jayavelu, Tamilselvan. No especifíca;Fil: Bruzzone, Santina. Università degli Studi di Genova; ItaliaFil: Mostoslavsky, Raul. Harvard Medical School; Estados UnidosFil: Sundaresan, Nagalingam R.. No especifíca

Female Sex and Gender in Lung/Sleep Health and Disease. Increased Understanding of Basic Biological, Pathophysiological, and Behavioral Mechanisms Leading to Better Health for Female Patients with Lung Disease

Female sex/gender is an undercharacterized variable in studies related to lung development and disease. Notwithstanding, many aspects of lung and sleep biology and pathobiology are impacted by female sex and female reproductive transitions. These may manifest as differential gene expression or peculiar organ development. Some conditions are more prevalent in women, such as asthma and insomnia, or, in the case of lymphangioleiomyomatosis, are seen almost exclusively in women. In other diseases, presentation differs, such as the higher frequency of exacerbations experienced by women with chronic obstructive pulmonary disease or greater cardiac morbidity among women with sleep-disordered breathing. Recent advances in -omics and behavioral science provide an opportunity to specifically address sex-based differences and explore research needs and opportunities that will elucidate biochemical pathways, thus enabling more targeted/personalized therapies. To explore the status of and opportunities for research in this area, the NHLBI, in partnership with the NIH Office of Research on Women's Health and the Office of Rare Diseases Research, convened a workshop of investigators in Bethesda, Maryland on September 18 and 19, 2017. At the workshop, the participants reviewed the current understanding of the biological, behavioral, and clinical implications of female sex and gender on lung and sleep health and disease, and formulated recommendations that address research gaps, with a view to achieving better health outcomes through more precise management of female patients with nonneoplastic lung disease. This report summarizes those discussions

Fertility, Pregnancy and Lactation Considerations for Women with CF in the CFTR Modulator Era

Cystic fibrosis (CF) is an autosomal recessive genetic disorder impacting approximately 80,000 people of all races and ethnicities world-wide. CF is caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene which encodes a protein of the same name. Protein dysfunction results in abnormal chloride and bicarbonate transport in mucus membranes, including those in the respiratory, gastrointestinal and reproductive tracts. Abnormal anion transport causes viscous secretions at the site of involvement. The majority of people with CF succumb to respiratory failure following recurrent cycles of infection and inflammation in the airways. Historically, providers treated the signs and symptoms of CF, but since 2012, have been able to impact the basic defect for the subset of people with CF who have mutations that respond to the new class of drugs, CFTR protein modulators. With the improved health and longevity afforded by CFTR modulators, more women are interested in parenthood and are becoming pregnant. Furthermore, this class of drugs likely increases fertility in women with CF. However, the safety of CFTR modulators in pregnancy and lactation is only beginning to be established. We summarize available data on the impact of CFTR modulators on fertility, pregnancy and lactation in women with CF

Antipyretic Activity of Hydroalcoholic Extract of Leaves of Colocasia esculenta

In this paper the antipyretic effect of the Hydroalcoholic extract of leaves of Colocasia esculenta against Brewer yeast induced pyrexia model in Wistar rats of either sex was investigated. Colocasia esculenta (Apiaceae) is a tropical perennial plant. It contain flavonoids, alkaloids, apigenin, anthocyanin, carbohydrates, fiber, minerals, protein, fat, calcium and iron, &nbsp;Fever induced in the animal (rats) by the injection 15%w/v of brewer’s yeast suspension (10mg/kg according to body weight of rats) subcutaneously in the back below the nape of the neck. . After 18 hr. of Brewer’s yeast injection and rise in rectal temperature was recorded. The temperature of animal was recorded at 0, 1, 2, 3 and 4hr after drug administration. Paracetamol (100 mg/kg p. o.) was used as standard drug. The group received Hydroalcoholic extract 200mg/kg and 400mg/kg showed significant decrease in rectal temperature respectively as compared with the group received standard drug. All the values are expressed as mean ± standard deviation and analysed for ANOVA. Differences between controls, standard ant test groups were considered significant at P &lt; 0.001 levels. . The Hydroalcoholic extract of Colocasia esculenta leaves (200mg/kg and 400mg/kg) possesses dose dependent, significant antipyretic activity against Brewer yeast induced pyrexia. Keywords: Antipyretic activity, ethanolic extract, Colocasia esculenta, Dunnet’s t –test, ANOVA

Teletherapy sources with imported and indigenous 60Co activity

Board of Radiation and Isotope Technology, a unit of the Department of Atomic Energy, fabricates and supplies radioactive sources for medical, industrial, agriculture and research applications. High specific activity cobalt-60, required for teletherapy is normally imported. There was a proposal for manufacturing high specific activity sources indigenously. A study was carried out to observe the feasibility of mixing imported and indigenous cobalt-60 pellets to fabricate teletherapy source capsules. The specific activity of imported pellets is more than 300 Ci/g, whereas that of indigenous pellets obtained from Indian power reactors is 140 Ci/g. The radiation output from a capsule for different combinations of specific activity was evaluated. Losses due to self-absorption were accounted in the evaluations. In another study, the optimized lengths of the capsule for an output of 200 RMM and the additional activity to be added to compensate losses due to self-absorption were also estimated for different specific activity pellets. Sources fabricated on the basis of this study showed a good agreement with the estimations. Source capsules with a combination of different specific activities are yet to be fabricated