Search

Objectives Polycystic ovary syndrome (PCOS) increases non-alcoholic fatty liver disease (NAFLD) risk and severity in adults, but data in adolescents with diverse backgrounds are limited. We evaluated NAFLD prevalence and characterized NAFLD risk factors in overweight/obese adolescents by PCOS status. Methods Retrospective study of overweight (n=52)/obese (n=271) female adolescents (12–18 years old), evaluated clinically 2012–2020, was conducted comparing PCOS patients to age-matched non-PCOS controls. NAFLD was defined as ALT≥44U/L x2 and/or ≥80U/L x1, hepatic steatosis on imaging, or NAFLD on biopsy, in absence of other liver disease. Metabolic comorbidities were captured. Log-binomial regression models estimated prevalence risk ratios (PR). Results NAFLD prevalence was 19.1 % in adolescents with PCOS (n=161), similar to those without (n=162) (16.8 %, p=0.6). Adolescents with PCOS were more likely to have insulin resistance, hypercholesterolemia, and higher triglycerides (p Conclusions Almost 1 in 5 overweight/obese female adolescents had NAFLD, but PCOS did not increase NAFLD risk in this diverse cohort. Among young women with PCOS, concomitant T2DM did increase the risk for NAFLD. Closer monitoring of obesity comorbidities in adolescents with PCOS is essential for optimizing health and merits updating current guidelines.

Curcumin (diferuloylmethane) derived from the rhizome of Curcuma longa L. has been an active ingredient of traditional Chinese medicine and Ayurvedic medicine for thousands of years to treat liver diseases, rheumatoid diseases, diabetes, atherosclerosis, infectious diseases and cancer. Curcumin has multiple essential pharmacological properties namely, antioxidant, anti-inflammatory, antimutagenic, antimicrobial and anticancer activity. Curcumin inhibits oxidative stress, angiogenesis and inflammatory processes and restore body homeostasis. Its effectiveness was also proved for major eye diseases. In this article, the influence of curcumin on various eye diseases such as dry eye disease, conjunctivitis, pterygium, anterior uveitis, glaucoma, cataract, age-related macular degeneration, diabetic retinopathy, corneal neovascularization, corneal wound healing are reported. Data analysis from several clinical and preclinical investigations indicate that curcumin is highly effective as a therapeutic agent in the treatment of various eye disorders.

The development of new anticancer agents is one of the most pressing research areas in medicinal chemistry and medicine. The importance of triazole and pyridine rings as scaffolds present in a wide range of therapeutic agents has been well reported and has driven the synthesis of a large number of novel anticancer agents. The presence of these heterocyclic furnishes extensive synthetic possibilities due to the presence of several reaction sites. Prompted by these data we designed, synthesized and evaluated a series of novel 1, 2, 4-triazole-pyridine hybrid derivatives as potential anticancer agents. To design and synthesize series of novel 1, 2, 4-triazole-pyridine hybrid derivatives as potential anticancer agents Derivatives were synthesized by the reaction of nicotinohydrazide with carbon disulfide to yield potassium-3-pyridyl-dithiocarbazate (I). This was further cyclized with ammonia solution to yield 5-mercapto-substituted 1, 2, 4-triazole-pyridine hybrid (II). This was finally reacted with different substituted benzyl derivatives to produce 1, 2, 4-triazole-pyridine hybrid derivatives (III). The purity of the derivatives was confirmed by thin-layer chromatography and melting point. Structure of these derivatives was set up by determining its infrared spectroscopy, nuclear magnetic resonance spectroscopy and mass spectroscopy. Further, the synthesized 1, 2, 4 triazole pyridine derivatives were tested for their in vitro anticancer activities against murine melanoma (B16F10) using the MTT reduction assay method. The cell viability study of synthesized compounds concludes that all compounds have moderate to potent anticancer activities against cancer cell lines. Compounds TP1-TP7 have IC in the range of 41.12μM to 61.11μM and the highest activity was observed for compound TP6 against murine melanoma (B16F10) cell line.Thepresent research may pave a way for the development of 1, 2, 4-triazole-pyridine as novel anticancer agents with good efficacy and lesser adverse effects.

The aim of the present research was to develop and evaluate the anti-microbial emulgel by using three different types of synthetic polymers. The active moiety selected for the formulation was the seeds of Carica papaya fruit. The formulation was developed by performing the extraction process; Soxhlet extraction with ethanol and water. The seeds of Carica papaya are reported to have anti-microbial properties. The skin-friendly i.e., the topical formulation was selected for development. Emulgel was prepared by incorporating different polymers and then evaluating each of them for best results. Basic evaluation parameters such as organoleptic parameters, viscosity, consistency, pH, homogeneity have been done, which demonstrate the results as per the reference and standard articles. Along with that, qualitative and quantitative tests of Carica seeds have also been performed, which indicates that the selected plant material is safe for usage. Finally, the most imp test, the anti-microbial test has been performed for determining the efficacy of prepared emulgel. Hence, it can be concluded that the prepared emulgel is safe and best for topical use as an anti-microbial.

ObjectiveNon-Alcoholic Fatty Liver Disease (NAFLD) is reported to be the most common chronic pediatric liver disease. Little information is available on the adherence of residents in-training to the published guidelines for the evaluation and management of pediatric NAFLD.The goals of this study are: (i) to assess the consistency of screening and evaluation for NAFLD in obese and overweight children at continuity clinics by upper level residents, and (ii) to determine the residents' extent of training, knowledge, comfort and competence levels in NAFLD care.MethodsAn electronic survey developed using REDCap was emailed to accredited Pediatric Residency Programs in the United States. Program directors and coordinators were requested to forward the survey to their upper level pediatric and medicine/pediatrics residents. Statistical analysis of responses (n= 399) was performed.ResultsMore than 88% of residents reported to be exposed to obese and overweight children, representing at least 25% of the patients encountered in clinics. Regardless of their training level, they inconsistently screened for (>60%), initiated evaluation of, or provided counseling on NAFLD in these patients, not following the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition guidelines. Over 80% of residents perceived to have received inadequate training resulting in insufficient knowledge on NAFLD, which they identified as their biggest barrier (25.7%). There was minimal statistically significant difference in the survey findings between training levels (PGY-2 vs PGY-3/4).ConclusionsEducational interventions should be implemented by pediatric residency programs to enhance educational core curricula for the early detection and initiation of management of NAFLD, an emerging public health problem.

Protein and peptide are last three decades therapeutic peptides and proteins have risen in prominence as potential drug of future. Polymers of protein consist of amino acids covalently linked by peptide bonds. Peptides are small proteins composed of up to a couple of dozen amino acids proteins are rapidly degraded by digestive enzymes. Till recently, injections remain the foremost common means for administering these protein and peptide drugs. In the other routes that have been tried with varying degrees of success are the oral, buccal, intranasal, pulmonary, transdermal, ocular and rectal. In this review, the aim is to specialise in the varied routes and approaches for delivery of Peptide and protein drugs. The Continuous efforts are focussed for formulation of this therapeutics into safe and effective delivery systems. In this review briefly describes the possible methods for the delivery of protein and peptide drugs through various routes.

Background/Objective \ud Patients classified as interstitial pneumonia with autoimmune features (IPAF) have interstitial lung disease (ILD) and features of autoimmunity but do not fulfill criteria for connective tissue diseases (CTDs). Our goal was to identify patients classifiable as IPAF, CTD-ILD, and idiopathic pulmonary fibrosis (IPF) from a preexisting pulmonary cohort and evaluate the prognosis of patients with IPAF.\ud \ud Methods \ud We reviewed the medical records of 456 patients from a single-center pulmonary ILD cohort whose diagnoses were previously established by a multidisciplinary panel that did not include rheumatologists. We reclassified patients as IPAF, CTD-ILD, or IPF. We compared transplant-free survival using Kaplan-Meier methods and identified prognostic factors using Cox models.\ud \ud Results \ud We identified 60 patients with IPAF, 113 with CTD-ILD, and 126 with IPF. Transplant-free survival of IPAF was not statistically significantly different from that of CTD-ILD or IPF. Among IPAF patients, male sex (hazard ratio, 4.58 [1.77–11.87]) was independently associated with worse transplant-free survival. During follow-up, only 10% of IPAF patients were diagnosed with CTD-ILD, most commonly antisynthetase syndrome.\ud \ud Conclusion \ud Despite similar clinical characteristics, most patients with IPAF did not progress to CTD-ILD; those who did often developed antisynthetase syndrome, highlighting the critical importance of comprehensive myositis autoantibody testing in this population. As in other types of ILD, male sex may portend a worse prognosis in IPAF. The routine engagement of rheumatologists in the multidisciplinary evaluation of ILD will help ensure the accurate classification of these patients and help clarify prognostic factors.

Among the hallmark achievements of the modern civilisation is the realisation and dissemination of knowledge that rights to life, liberty and security of persons are primary inherent and inalienable to every human being irrespective of individual’s race, nationality, economic status along with manmade discriminations. India, despite of all the diversified cultural fabrics in the preamble the grundnorm pledged to maintain the essence of secularism. Being a secular nation, India has developed personal codified legislations governing the particular religions. The anti-Hindu sentiment which articulates, advances, and amplifies hatred against Hinduism and Hindus is known as Hindu phobia. This write-up attempts to bring out the contemporaneous of the topic and acknowledge the Hindu phobic provisions and legislations in the nation, specifically the Right to Education and Article 30 of our constitution. Lastly it alludes the issue of ‘Love Jihad’ as a threat to humanitarians along with the stance of India in UN.

Background: Interstitial Lung Disease [ILD] patients requiring Invasive Mechanical Ventilation [IMV] for Acute Respiratory Failure [ARF] are known to have a poor prognosis. Few studies have investigated determinants of outcomes and the utility of trialing Non-Invasive Positive Pressure Ventilation [NIPPV] prior to IMV to see if there are any effect[s] on mortality or morbidity. Methods: A retrospective study was designed using patients at four different intensive care units within one health care system. The primary objective was to determine if there are differences in outcomes for in-hospital and one-year mortality between patients who undergo NIPPV prior to IMV and those who receive only IMV. A secondary objective was to identify potential determinants of outcomes. Results: Out of 54 ILD patients with ARF treated with IMV, 20 (37.0%) survived until hospital discharge and 10 (18.5%) were alive at one-year. There was no significant mortality difference between patients trialed on NIPPV prior to IMV and those receiving only IMV. Several key determinants of outcomes were identified with higher mortality, including higher ventilatory support, idiopathic pulmonary fibrosis (IPF) subtype, high dose steroids, use of vasopressors, supraventricular tachycardias (SVTs), and higher body mass index. Conclusion: Considering that patients trialed on NIPPV prior to IMV were associated with no mortality disadvantage to patients treated with only IMV, trialing patients on NIPPV may identify responders and avoid complications associated with IMV. Increased ventilator support, need of vasopressors, SVTs, and high dose steroids reflect higher mortality and palliative care involvement should be considered as early as possible if a lung transplant is not an option.

Dysmenorrhoea is the most common Gynaecological problem with painful menstruation due to increased levels of prostaglandins in the menstrual fluid, this results in uterine pain, nausea, vomiting, backache, diar-rhoea, giddiness, syncope and fainting. In Ayurveda it is explained in terms of "Kashtartava", which is clinical entity characterized by pain and difficult expulsion of Aartva (Menstrual Blood) due to upward movement of Raja (Menstrual Blood), through Pratiloma Gati (Movement in reverse direction) of Apana Vayu and subsides after expulsion of Artava. Formation of Artava (Menstrual Blood) takes place during entire month, due to continuous filling of Garbhashaya through small capillaries, which is brought into Yo-ni and makes it to discharge outside every month by Vayu. The whole mechanism depends upon the proper functioning of Apana and Vyana Vayu where in Apana Vayu is responsible for Raja Pravritii while Vyana Vayu is accountable for blood circulation. In clinical intervention study, purposive randomly selected 40 patients were equally divided into 2 groups i.e. Group A (Trial Group) and Group B (Control Group). In Trial Group Rajahpravartini Vati in dose 250 mg twice a day and in Control Group Placebo (Roasted wheat flour) 2 Capsule twice a day were advised for treatment. drug administration was started from 21st day of LMP to next 3 days of menstrual cycle for duration of consecutively 3 menstrual cycles. It was found that average percentage of relief was higher in group A i.e. 71% while in group B i.e. 43.10%.

Iris cysts are not common and can provide a challenge for clinicians in terms of diagnosis and management. Iris is the colored muscular diaphragm with a circular central aperture forming the pupil. It is uveal tissue composed of stroma anteriorly and two layers of pigment epithelial cells posteriorly.

“purnamiv tailpatra samkshobhayad garbhinim upachared iti” The famous verse of our Ayurveda science that depicts a pregnant woman like a pot filled with oil where slight oscillation may cause spillage likewise even a slight carelessness results in adverse outcome” and especially in this COVID era where it is causing great harm to human population, it becomes very important to safeguard pregnant ladies so that true healthy babies can be delivered. It has been proven that vaccination and treatment protocols are safe for pregnant ones but the psychological effect is also one of the important factors to be considered which is generally absent in contemporary medicine. So heading towards Ayurveda science can definitely lead us to better motherhood and their healthy child’s.

BACKGROUND The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral PARP1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy. Preclinical data indicates that veliparib crosses the blood-brain-barrier and enhances the efficacy of radiotherapy and temozolomide in IDH mutant and wild-type HGG models. ACNS1721 was a single-arm, non-randomized phase 2 clinical trial designed to determine whether treatment with veliparib and radiotherapy, followed by the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib and temozolomide, improves progression-free survival (PFS) in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations compared to patient level data from historical cohorts with closely matching clinical and molecular features. METHODS Following surgical resection, newly diagnosed children with non-metastatic HGG were screened by rapid central pathology review and molecular testing. Eligible patients without somatic H3 K27M or BRAF mutations were enrolled on Stratum 1 (IDH wild-type) or Stratum 2 (IDH mutant). Protocol radiochemotherapy consisted of involved field radiotherapy with concurrent veliparib at 65 mg/m2 twice daily. Adjuvant chemotherapy consisted of up to 10 cycles of veliparib 25 mg/m2 twice daily and temozolomide 135 mg/m2 once daily for 5 days every 4 weeks. RESULTS Both strata were closed to accrual for futility after planned interim analyses. Among the 23 eligible patients who enrolled on Stratum 1 and received protocol therapy, the 1-year progression-free survival (PFS) was 0.29 (SE = 0.09) and 1-year overall survival (OS) was 0.67 (SE = 0.10). Among the 14 eligible patients who enrolled on Stratum 2 and received protocol therapy, the 1-year PFS was 0.57 (SE = 0.15) and 1-year OS was 0.90 (SE = 0.09). CONCLUSION Rapid central pathology review and molecular testing was feasible. The protocol therapy was well tolerated but failed to improve outcome compared to clinically and molecularly matched historical control cohorts.

BACKGROUND: The outcome for pediatric patients with high-grade glioma (HGG) remains poor. Veliparib, a potent oral PARP1/2 inhibitor, enhances the activity of radiotherapy and DNA-damaging chemotherapy. Preclinical data indicates that veliparib crosses the blood-brain-barrier and enhances the efficacy of radiotherapy and temozolomide in IDH mutant and wild-type HGG models. ACNS1721 was a single-arm, non-randomized phase 2 clinical trial designed to determine whether treatment with veliparib and radiotherapy, followed by the poly (ADP-ribose) polymerase (PARP) inhibitor veliparib and temozolomide, improves progression-free survival (PFS) in pediatric patients with newly diagnosed HGG without H3 K27M or BRAF mutations compared to patient level data from historical cohorts with closely matching clinical and molecular features. METHODS: Following surgical resection, newly diagnosed children with non-metastatic HGG were screened by rapid central pathology review and molecular testing. Eligible patients without somatic H3 K27M or BRAF mutations were enrolled on Stratum 1 (IDH wild-type) or Stratum 2 (IDH mutant). Protocol radiochemotherapy consisted of involved field radiotherapy with concurrent veliparib at 65 mg/m2 twice daily. Adjuvant chemotherapy consisted of up to 10 cycles of veliparib 25 mg/m2 twice daily and temozolomide 135 mg/m2 once daily for 5 days every 4 weeks. RESULTS: Both strata were closed to accrual for futility after planned interim analyses. Among the 23 eligible patients who enrolled on Stratum 1 and received protocol therapy, the 1-year progression-free survival (PFS) was 0.29 (SE = 0.09) and 1-year overall survival (OS) was 0.67 (SE = 0.10). Among the 14 eligible patients who enrolled on Stratum 2 and received protocol therapy, the 1-year PFS was 0.57 (SE = 0.15) and 1-year OS was 0.90 (SE = 0.09). CONCLUSION: Rapid central pathology review and molecular testing was feasible. The protocol therapy was well tolerated but failed to improve outcome compared to clinically and molecularly matched historical control cohorts.

It is unknown whether some donor specific antibodies (DSA) can be crossed at the time of lung transplant without desensitization or augmented induction immunosuppression. This study assessed whether crossing low-level pre-transplant DSA (defined as mean fluorescence intensity (MFI) 1000-6000) without augmented immunosuppression is associated with worse retransplant-free or chronic lung allograft dysfunction (CLAD)-free survival. Of the 458 included recipients, low-level pre-transplant DSA was crossed in 39 (8.6%) patients. The median follow-up time was 2.2 years. There were 15 (38.5%) patients with Class I DSA and 24 (61.5%) with Class II DSA. There was no difference in adjusted overall retransplant-free survival between recipients where pre-transplant DSA was and was not crossed (HR: 0.98 (95% CI = 0.49-1.99), p = 0.96). There was also no difference in CLAD-free survival (HR: 0.71 (95% CI = 0.38-1.33), p = 0.28). There was no difference in Grade 3 PGD at 72 hours (OR: 1.13 (95% CI = 0.52-2.48), p = 0.75) or definite or probable AMR (HR: 2.22 (95% CI = 0.64-7.61), p = 0.21). Lung transplantation in the presence of low-level DSA without planned augmented immunosuppression is not associated with worse overall or CLAD-free survival among recipients with intermediate-term follow-up. This article is protected by copyright. All rights reserved.

Women with advanced lung disease, particularly Black and Hispanic women, are more likely than other patients to have anti-human leukocyte (HLA) antibodies against potential donors. Sensitized patients, especially those who are highly sensitized, are less likely to be listed for lung transplant or to be considered candidates for mechanical circulatory support. They are also at higher risk for waitlist death. Institutional variability in approach to HLA antibody screening and pre-transplant management creates barriers to transplant that disproportionately impact Black and Hispanic women. At the same time, our understanding of the clinical significance of pre-transplant antibodies lags behind the sophistication of our screening assays. The lack of national data on pre- and post-transplant HLA antibody characteristics hinders research into strategies to mitigate concerns about these antibodies and to improve access to lung transplant among sensitized patients. Ongoing work should be done to identify clinically higher risk antibodies, to develop better strategies for safely crossing antibodies at the time of transplant, and to model changes in lung allocation to give priority to sensitized patients for a HLA antibody-antigen compatible donors. These priorities mandate a commitment to collaborative, multicenter research and to real time translation of results to clinical practice and allocation policy.

Elucidation of non-canonical protein functions can identify novel tissue homeostasis pathways. Herein, we describe a role for the Bcl-2 family member BAD in postnatal mammary gland morphogenesis. In Bad3SA knock-in mice, where BAD cannot undergo phosphorylation at 3 key serine residues, pubertal gland development is delayed due to aberrant tubulogenesis of the ductal epithelium. Proteomic and RPPA analyses identify that BAD regulates focal adhesions and the mRNA translation repressor, 4E-BP1. These results suggest that BAD modulates localized translation that drives focal adhesion maturation and cell motility. Consistent with this, cells within Bad3SA organoids contain unstable protrusions with decreased compartmentalized mRNA translation and focal adhesions, and exhibit reduced cell migration and tubulogenesis. Critically, protrusion stability is rescued by 4E-BP1 depletion. Together our results confirm an unexpected role of BAD in controlling localized translation and cell migration during mammary gland development., Preventing phosphorylation of BAD (3SA) in mouse models and human cells inhibits mammary gland development, acting by disrupting 4E-BP1- mediated translation and affecting focal adhesion/protrusion stability, cell migration and ductal tubulogenesis.

The walking catfish Clarias magur (Hamilton, 1822) (magur) is an important catfish species inhabiting the Indian subcontinent. It is considered as a highly nutritious food fish and has the capability to walk to some distance, and survive a considerable period without water. Assembly, scaffolding and several rounds of iterations resulted in 3,484 scaffolds covering ∼94% of estimated genome with 9.88 Mb largest scaffold, and N50 1.31 Mb. The genome possessed 23,748 predicted protein encoding genes with annotation of 19,279 orthologous genes. A total of 166 orthologous groups represented by 222 genes were found to be unique for this species. The Computational Analysis of gene Family Evolution (CAFE) analysis revealed expansion of 207 gene families and 100 gene families have rapidly evolved. Genes specific to important environmental and terrestrial adaptation, viz. urea cycle, vision, locomotion, olfactory and vomeronasal receptors, immune system, anti-microbial properties, mucus, thermoregulation, osmoregulation, air-breathing, detoxification, etc. were identified and critically analysed. The analysis clearly indicated that C. magur genome possessed several unique and duplicate genes similar to that of terrestrial or amphibians’ counterparts in comparison to other teleostean species. The genome information will be useful in conservation genetics, not only for this species but will also be very helpful in such studies in other catfishes.

ObjectiveThe growing shortage of neurologists is in part due to suboptimal recruitment. Little is known about students' decision making regarding a career in neurology, particularly early in training. Using a longitudinal qualitative approach, we aimed to understand factors that influence first-year medical students' decisions about neurology.MethodsWe conducted 1-on-1 semistructured interviews with 15 first-year medical students at 1 institution before and after the preclinical neurology course (2018–2019). In the first interview, we asked about career intentions, factors likely to influence specialty choice, and perceptions of neurology. In the second interview, we asked about changes in students' views over the year. Using thematic analysis, we generated codes and clustered coded data into themes.ResultsThe 2 most prominent factors influencing career choice in general were lifestyle and personal interest. No students expressed concerns about lifestyle in neurology. Most students were neutral about neurology or had a positive personal interest, which typically increased after the neurology course. Students frequently worried about content difficulty and the curative potential of neurology.ConclusionsInterventions should include early education about the factors important to students in determining specialty choice, including lifestyle, and address potentially negative perceptions of neurology. Increasing time allotment to the preclinical neurology course may combat perception of the content as difficult.

The Bcl-2-associated death promoter BAD is a prognostic indicator for good clinical outcome of breast cancer patients; however, whether BAD affects breast cancer biology is unknown. Here we showed that BAD increased cell growth in breast cancer cells through two distinct mechanisms. Phosphorylation of BAD at S118 increased S99 phosphorylation, 14-3-3 binding and AKT activation to promote growth and survival. Through a second, more prominent pathway, BAD stimulated mitochondrial oxygen consumption in a novel manner that was downstream of substrate entry into the mitochondria. BAD stimulated complex I activity that facilitated enhanced cell growth and sensitized cells to apoptosis in response to complex I blockade. We propose that this dependence on oxidative metabolism generated large but nonaggressive cancers. This model identifies a non-canonical role for BAD and reconciles BAD-mediated tumor growth with favorable outcomes in BAD-high breast cancer patients.

Background Unplanned rehospitalizations (UR) within 30 days of discharge are common after lung transplantation. It is unknown whether UR represents preventable gaps in care or necessary interventions for complex patients. The objective of this study was to assess the incidence, causes, risk factors, and preventability of UR after initial discharge after lung transplantation. Methods This was a single-center prospective cohort study. Subjects completed a modified short physical performance battery to assess frailty at listing and at initial hospital discharge after transplantation and the State-Trait Anxiety Inventory at discharge. For each UR, a study staff member and the patient's admitting or attending clinician used an ordinal scale (0, not; 1, possibly; 2, definitely preventable) to rate readmission preventability. A total sum score of 2 or higher defined a preventable UR. Results Of the 90 enrolled patients, 30 (33.3%) had an UR. The single most common reasons were infection (7 [23.3%]) and atrial tachyarrhythmia (5 [16.7%]). Among the 30 URs, 9 (30.0%) were deemed preventable. Unplanned rehospitalization that happened before day 30 were more likely to be considered preventable than those between days 30 and 90 (30.0% versus 6.2%, P = 0.04). Discharge frailty, defined as short physical performance battery less than 6, was the only variable associated with UR on multivariable analysis (odds ratio, 3.4; 95% confidence interval, 1.1-11.8; P = 0.04). Conclusions Although clinicians do not rate the majority of UR after lung transplant as preventable, discharge frailty is associated with UR. Further research should identify whether modification of discharge frailty can reduce UR.

Purpose Lung transplant recipients with pre-transplant donor specific antibodies (DSA) are often treated with augmented immunosuppression. It is unknown whether some DSA can be safely crossed without additional therapies. We implemented a protocol allowing transplant when crossing select low level DSA (defined as mean fluorescence intensity (MFI) 1000-5000) without planned augmented immunosuppression. Methods This was a single center retrospective cohort study between 4/1/2015-8/31/2020. All recipients received solumedrol and basiliximab induction without desensitization. Presence of low level pre-transplant DSA was recorded. All post-transplant DSA was monitored within 14 days of transplant and then at routine intervals. The primary study outcomes were overall survival, definite CLAD≥1-free survival, and definite antibody mediated rejection (AMR), all defined according to ISHLT consensus guidelines. Results Of the 453 recipients, 36 (7.9%) had a low-level pre-transplant DSA crossed at transplant (Table 1). 13 had Class I antibodies and 26 had Class II. The median historical DSA MFI was 1800 (IQR 1300-2400) and the median most recent MFI was 1200 (IQR 950-2000). Among recipients where pre-transplant DSA was crossed, 17 (47.2%) had persistent post-transplant DSA with a median peak MFI of 7400. Class II antibodies were more likely to be detected post-transplant than Class I (57.7% vs 15.4%, p=0.02). There was no statistical difference in definite AMR in recipients where pre-transplant DSA was and was not crossed (8.3% vs 3.1%, p=0.11). With a median follow-up time of 2.4 years, there were no differences in adjusted overall survival (HR=1.14, 95% CI=0.57-2.32, p=0.71) or CLAD≥1-free survival (HR=0.82, 95% CI=0.44-1.54, p=0.54). Conclusion Lung transplantation in the presence of low level DSA without planned augmented immunosuppression was not associated with worse overall or CLAD-free intermediate-term survival but may be associated with increased AMR.

Cloud Computing is an example of the distributed system where the end user has to connect to the services given by the cloud which is maintained by the cloud service provider (CSP). The user has to have certain trust upon the cloud as finally, the end user has to migrate the jobs into the cloud of some third party, as the on-premises data or sources are to be kept across the globe, the CSP have to maintain the trust level so that the end user can opt for the services given by the certain trusted Cloud. Ultimately there will be various elements of levels happening at the CSP side to maintain the trust level, like the safety features for security has to be identified, federation related or Virtual Machine migration techniques status has to be always monitored to maintain and avoid certain uncertainty which will affect the trust level of the cloud, which can lead to the compromised situation in between the end user and CSP, as a result the trust value will decrease, In this paper we are proposing a techniques where the security features and conditions for load balancing monitoring technique with proactive actions will be analyzed to maintain the specified trust level.

Apoptosis is fundamental to normal animal development and is the target for many anticancer therapies. Recent studies have explored the consequences of “failed apoptosis” where the apoptotic program is initiated but does not go to completion and does not cause cell death. Nevertheless, this failed apoptosis induces DNA double-strand breaks generating mutations that facilitate tumorigenesis. Whether failed apoptosis is relevant to clinical disease is unknown. BCL-2 interacting killer (BIK) is a stress-induced BH3-only protein that stimulates apoptosis in response to hormone and growth factor deprivation, hypoxia, and genomic stress. It was unclear whether BIK promotes or suppresses tumor survival within the context of breast cancer. We investigated this and show that BIK induces failed apoptosis with limited caspase activation and genomic damage in the absence of extensive cell death. Surviving cells acquire aggressive phenotypes characterized by enrichment of cancer stem-like cells, increased motility and increased clonogenic survival. Furthermore, by examining six independent cohorts of patients (total n = 969), we discovered that high BIK mRNA and protein levels predicted clinical relapse of Estrogen receptor (ER)-positive cancers, which account for almost 70% of all breast cancers diagnosed but had no predictive value for hormone receptor-negative (triple-negative) patients. Thus, this study identifies BIK as a biomarker for tumor recurrence of ER-positive patients and provides a potential mechanism whereby failed apoptosis contributes to cancer aggression.

EgeUn###, Rationale: Several common and rare genetic variants have been associated with idiopathic pulmonary fibrosis, a progressive fibrotic condition that is localized to the lung. Objectives: To develop an integrated understanding of the rare and common variants located in multiple loci that have been reported to contribute to the risk of disease. Methods: We performed deep targeted resequencing (3.69 Mb of DNA) in cases (n = 3,624) and control subjects (n = 4,442) across genes and regions previously associated with disease. We tested for associations between disease and 1) individual common variants via logistic regression and 2) groups of rare variants via sequence kernel association tests. Measurements and Main Results: Statistically significant common variant association signals occurred in all 10 of the regions chosen based on genome-wide association studies. The strongest risk variant is the MUC5B promoter variant rs35705950, with an odds ratio of 5.45 (95% confidence interval, 4.91-6.06) for one copy of the risk allele and 18.68 (95% confidence interval, 13.34-26.17) for two copies of the risk allele (P = 9.60 3 102295). In addition to identifying for the first time that rare variation in FAM13A is associated with disease, we confirmed the role of rare variation in the TERT and RTEL1 gene regions in the risk of IPF, and found that the FAM13A and TERT regions have independent common and rare variant signals. Conclusions: A limited number of common and rare variants contribute to the risk of idiopathic pulmonary fibrosis in each of the resequencing regions, and these genetic variants focus on biological mechanisms of host defense and cell senescence. Copyright © 2019 by the American Thoracic Society, Háskóli Íslands, HI University of Chicago University of Ulsan, UOU Monash University, MU University of Nottingham University of Edinburgh University of Colorado Denver Universitat de Barcelona University of Pittsburgh, Pitt Harvard School of Dental Medicine Massachusetts General Hospital, MGH University of Pennsylvania, Penn University College Cork, UCC City, University of London, City University of California, San Francisco, UCSF School of Medicine, Vanderbilt University Ege Üniversitesi University of Virginia, UV Aarhus Universitetshospital Central Manchester University Hospitals NHS Foundation Trust Columbia University Novartis Sunovion COPD Foundation Pfizer National Heart, Lung, and Blood Institute, NHLBI: R01-HL097163, UH3-HL123442, P01-HL092870 U.S. Department of Defense, DOD: W81XWH-17-1-0597, U01 HL089897, U01 HL089856 AstraZeneca Siemens Foundation North Carolina GlaxoSmithKline Foundation, 1National Jewish Health, Denver, Colorado; 2School of Public Health; 3Department of Medicine, and 54Department of Immunology, University of Colorado Denver, Denver, Colorado; 4Department of Medicine, Vanderbilt University School of Medicine, Nashville, Tennessee; 5Brigham and Women’s Hospital, Harvard School of Medicine, Boston, Massachusetts; 6Oklahoma Medical Research Foundation, Oklahoma City, Oklahoma;7Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 8MRC Centre for Inflammation Research, University of Edinburgh, Edinburgh, United Kingdom; 9Respiratory Medicine Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom; 10Biomedical Research Centre, University of Nottingham, Nottingham, United Kingdom; 11Royal Brompton Hospital and Imperial College, London, United Kingdom; 12Simmons Center for Interstitial Lung Disease, University of Pittsburgh, Pittsburgh, Pennsylvania; 13Department of Medicine, University of California, San Francisco, San Francisco, California; 14Gilead Sciences, Foster City, California; 15Department of Medicine, University of Chicago, Chicago, Illinois; 16Department of Medicine, University of Virginia, Charlottesville, Virginia; 17Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania; 18National Hospital Organization Kinki-Chuo Chest Medical Center, Osaka, Japan; 19National Hospital Organization Tokyo National Hospital, Tokyo, Japan; 20Helmholtz Zentrum München, Neuherberg, Germany; 21University Hospital Munich, Munich, Germany; 22Department of Pulmonology, Ege University Hospital, Bornova, Izmir, Turkey; 23Royal Prince Alfred Hospital and University of Sydney, Sydney, Australia; 24Alfred Hospital and Monash University, Melbourne, Australia; 25Pulmonary Medicine, GB Morgagni Hospital, Forlì, Italy; 26Department of Diseases of the Thorax, Ospedale GB Morgagni, Forlì, Italy; 27Université Paris Diderot and Hôpital Bichat, Paris, France; 28Royal Papworth Hospital and Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 29Respiratory Department, University Hospital of Bellvitge, University of Barcelona, Barcelona, Spain; 30National University Hospital of Iceland, University of Iceland, Reykjavik, Iceland; 31Department of Medicine, Columbia University Irving Medical Center, New York, New York; 32Division of Pulmonary and Critical Care Medicine, Massachusetts General Hospital, Boston, Massachusetts; 33Department of Respiratory Diseases and Allergy, Aarhus University Hospital, Aarhus, Denmark; 34Instituto Nacional de Enfermedades Respiratorias “Ismael Cosio Villegas,” México City, México; 35Universidad Nacional Autónoma de México, México City, México; 36Cork University Hospital and University College Cork, Cork, Ireland; 37St. Vincent’s University Hospital, Dublin, Ireland; 38School of Medicine, University College Dublin, Dublin, Ireland; 39Department of Respiratory Medicine, First Faculty of Medicine Charles University and Thomayer Hospital, Prague, Czech Republic; 40University of British Columbia, Vancouver, Canada; 41Tokyo Medical and Dental University, Tokyo, Japan; 42Institute for Respiratory Health and; 43Centre for Cell Therapy and Regenerative Medicine, School of Biomedical Sciences, The University of Western Australia, Perth, Australia; 44Department of Medicine, Warren Alpert Medical School of Brown University, Providence, Rhode Island; 45Advanced Lung Disease and Transplant Program, Inova Fairfax Hospital, Falls Church, Virginia; 46Department of Pulmonary Medicine, Gazi University School of Medicine, Ankara, Turkey; 47Department of Medicine, University of Alabama at Birmingham, Birmingham, Alabama; 48Ruhrlandklinik, University Hospital, University of Duisburg-Essen, Essen, Germany; 49Department of Medicine, Tallaght University Hospital, Trinity College Dublin, Dublin, Ireland; 50CardioPulmonary Reserach Center, Alliance Pulmonary Group, Guaynabo, Puerto Rico; 51Department of Internal Medicine, University of Genoa, Genoa, Italy; 52Biomedical Genomics Center, University of Minnesota; Minneapolis, Minnesota; and 53Northwest Genomics Center, University of Washington, Seattle, Washington -- This research was supported by grants from the NHLBI (R01-HL097163, P01-HL092870, and UH3-HL123442) and the Department of Defense (W81XWH-17-1-0597). The COPDGene project was supported by Award Number U01 HL089897 and Award Number U01 HL089856 from the NHLBI. The COPDGene project was also supported by the COPD Foundation through contributions made to an industry advisory board comprised of AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Pfizer, Siemens, and Sunovion.

The mahseers (Tor, Neolissochilus and Naziritor) are an important group of fishes endemic to Asia with the conservation status of most species evaluated as threatened. Conservation plans to revive these declining wild populations are hindered by unstable taxonomy. Molecular phylogeny studies with mitochondrial genome have been successfully used to reconstruct the phylogenetic tree and to resolve taxonomic ambiguity. In the present study, complete mitochondrial genome of Tor tor has been sequenced using ion torrent next-generation sequencing platform with coverage of more than 1000 x. Comparative mitogenome analysis shows higher divergence value at ND1 gene than COI gene. Further, occurrence of a distinct genetic lineage of T. tor is revealed. The phylogenetic relationship among mahseer group has been defined as Neolissochilus hexagonolepis ((T. sinensis (T. putitora, T. tor), (T. khudree, T. tambroides)).

We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk-adjusted all-cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no-induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67-0.95, p = 0.009) and basiliximab induction (0.88, 0.80-0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS.

Macrobrachium rosenbergii is an aquaculture species of global importance whose production has sharply declined since 2005. Single nucleotide polymorphisms (SNPs) in transcribed sequences are likely to have high association with economic traits and are important for marker assisted selection. SNPs were mined in 34 reported transcripts from 4 wild M. rosenbergii stocks of India using the amplicon approach and high-throughput sequencing platforms. Out of 320 SNPs detected, 134 were common to all stocks while 3 were diagnostic. Pair-wise Nei’s genetic distances (0.304–0.469) showed phylogeny consistent with geographical distribution. AMOVA analysis revealed estimated variance of 21.5 among populations. The transition to transversion ratio was 2.20. Changes in amino acid classes and peptide stability were recorded for 80 non-synonymous SNPs while change in codon preference was noted for 138 synonymous ones. Four pathogen defence genes were highly polymorphic, of which lectin 3 had the highest SNP rate (6 SNPs/100 bp). This approach for mining SNPs and using them for population differentiation in a single step is reported for the first time.