Search

Bovine mastitis is a complex infectious disease that develops in the mammary gland, predominantly caused by a bacterial infection of mammary tissue. Genetic variability of mastitis is well established and depends upon different quantitative trait loci (QTL) related to mastitis resistance or susceptibility. The susceptibility is often attributed to single-nucleotide polymorphisms (SNPs) in the variable cow breed genomes. Several global investigative attempts have resulted in studies mapping mastitis to the variations in the relevant genes. Reports have been attributed to dramatic genetic expression changes in Toll-Like Receptor 4 (TLR4) genes in mastitis-positive cows. However, the mechanism behind this variable genetic expression of TLR4 genes has been studied poorly. The present study aims to investigate SCM through various screening tests like somatic cell count (SCC), electric conductivity (EC), pH, and California mastitis test (CMT) in milk samples. This study also aims to investigate possible mechanisms behind this variable expression of TLR4 by comparative SNP evaluation and transcriptional factor profile mining. So that the important genetic mutations and effects thereof can be exploited in selecting specific breeds with higher mastitis resistance and milk yield. Seventy Holstein Frisian (HF) crossbred dairy cows were selected in the present study. The animals were screened based on various diagnostic tests (SCC, pH, EC, and CMT). Blood samples (5 mL) were collected for extraction of DNA followed by amplification of PPR1 and PPR2 of the promoter region and 5'UTR of the bovine TLR4 gene using specific primers. Sanger's enzymatic DNA sequencing technique sequenced the amplified PCR products. Further, the identification of SNPs was done through various bioinformatic tools used in this study. The findings of the present study revealed that CMT, EC, pH, and SCC could be used for the early detection of subclinical mastitis. In the present study, a significant increase in the EC, pH, and SCC in milk samples of animals affected with SCM was found in comparison to the healthy animals. The present study also revealed 16 SNPs falling in TLR4 promoter and 5' untranslated region (5'UTR) sequences in mastitis-positive genotypes compared to reference genomes. The study also investigates the potential transcriptional factor program deployed in response to variable mastitis development resistance. In the present study, the allelic and genotype frequencies of all SNP variants in the three regions viz., PPR1, PPR2, and 5'UTR, were the same indicating the absence of heterozygous condition at the respective loci. The present study has wide applicability for researchers developing mastitis-resistant breeding programs and the data generated may aid in the selection of better genetic breeds. The transcription factor binding profiles can serve as concrete leads about the studies on bovine mastitis at the molecular level and may also aid global research groups working on transcription factor (TF)-based molecular pathology of mastitis., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In this prospective, interventional phase 1 study for individuals with advanced sarcoma, we infused autologous HER2-specific chimeric antigen receptor T cells (HER2 CAR T cells) after lymphodepletion with fludarabine (Flu) ± cyclophosphamide (Cy): 1 × 10 8 T cells per m 2 after Flu (cohort A) or Flu/Cy (cohort B) and 1 × 10 8 CAR + T cells per m 2 after Flu/Cy (cohort C). The primary outcome was assessment of safety of one dose of HER2 CAR T cells after lymphodepletion. Determination of antitumor responses was the secondary outcome. Thirteen individuals were treated in 14 enrollments, and seven received multiple infusions. HER2 CAR T cells expanded after 19 of 21 infusions. Nine of 12 individuals in cohorts A and B developed grade 1-2 cytokine release syndrome. Two individuals in cohort C experienced dose-limiting toxicity with grade 3-4 cytokine release syndrome. Antitumor activity was observed with clinical benefit in 50% of individuals treated. The tumor samples analyzed showed spatial heterogeneity of immune cells and clustering by sarcoma type and by treatment response. Our results affirm HER2 as a CAR T cell target and demonstrate the safety of this therapeutic approach in sarcoma. ClinicalTrials.gov registration: NCT00902044 ., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

BACKGROUND Idiopathic giant cell myocarditis (IGCM) is an uncommon and frequently fatal type of myocarditis. It primarily affects young individuals and has the potential to result in heart failure and life-threatening arrhythmias. IGCM seems to be dependent on activation of CD4-positive T lymphocytes and can show improvement with treatment aimed at reducing T-cell function. We present a case of a 65-year-old patient who presented with features of acute heart failure refractory to guideline-directed medical therapy (GDMT), due to IGCM. A review of the natural history and treatment of IGCM is also presented. CASE REPORT A 65-year-old woman with multiple comorbidities was admitted to our hospital for ventricular tachycardia in the setting of progressive non-ischemic heart failure, unresponsive to GDMT. This led to further investigation, including an endomyocardial biopsy, which revealed inflammatory infiltration, with multinucleated giant cells and lymphocytes in the absence of granuloma formation, prompting a diagnosis of IGCM. An implantable cardioverter-defibrillator (ICD) was placed for secondary prevention of sudden cardiac death and the patient was initiated on combined immunosuppressive therapy. Owing to numerous comorbidities, she was determined to be unsuitable for a heart transplant. Unfortunately, she eventually died from complications secondary to the disease. CONCLUSIONS IGCM remains a challenging clinical diagnosis with a poor long-term outcome without heart transplantation. This case highlights the importance of considering atypical causes of heart failure in patients who do not respond to conventional therapies. Early recognition and appropriate management, involving medical and interventional approaches, are crucial in improving outcomes for patients with IGCM.

This study aims to determine whether serum Beta hCG can be used as a tumour marker in Breast malignancies. The objective of this study is to evaluate the serum Beta hCG in various stages of breast carcinoma and to correlate its level with disease severity and prognosis. Cross sectional analytical study of assessing serum Beta hCG in 200 patients with palpable breast malignancies at hospitals in urban Mangalore, India. In our study there was No increase in serum Beta hCG, in women with breast malignancies, but there was a pattern amongst the negative results. A Beta hCG of < 5mIU/mL is taken as negative, but in our study of 200 individuals, a mean value of 2mIU/mL was used as differentiation between low and high risk individuals. With our study we tried to correlate the value of Beta hCG with malignant breast lesions, and even though women with such lesions did not have a value of > 5mIU/mL, we found substantial evidence that women who had a value of > 2mIU/mL had a more advanced disease, be it in terms of staging, and comparing it with markers like ki67. A direct correlation between Beta hCG and severity of the disease in terms of staging was proved, hereby directly affecting the outcome of patients. Higher the level of Beta hCG, graver the prognosis. Even though Beta hCG cannot be used as tumour marker, it can be used to prognosticate the severity in women with palpable breast malignancies., (© 2023. Springer Nature Limited.)

Melatonin is ubiquitous molecule with wide distribution in nature and is produced by many living organisms. In human beings, pineal gland is the major site for melatonin production and to lesser extent by retina, lymphocytes, bone marrow, gastrointestinal tract, and thymus. Melatonin as a neurohormone is released into circulation wherein it penetrates all tissues of the body. Melatonin synthesis and secretion is supressed by light and enhanced by dark. Melatonin mostly exerts its effect through different pathways with melatonin receptor 1 (MT1) and melatonin receptor 2 (MT2) being the predominant type of receptor that are mainly expressed by many mammalian organs. Melatonin helps to regulate sleep patterns and circadian rhythms. In addition, melatonin acts as an antioxidant and scavenges excessive free radicals generated in the body by anti-excitatory and anti-inflammatory properties. A multiple array of other functions are displayed by melatonin that include oncostatic, hypnotic, immune regulation, reproduction, puberty timing, mood disorders, and transplantation. Deficiencies in the production or synthesis of melatonin have been found to be associated with onset of many disorders like breast cancer and neurodegenerative disorders. Melatonin could be used as potential analgesic drug in diseases associated with pain and it has quite promising role there. In the past century, a growing interest has been developed regarding the wide use of melatonin in treating various diseases like inflammatory, gastrointestinal, cancer, mood disorders, and others. Several melatonin agonists have been synthesized and are widely used in disease treatment. In this review, an effort has been made to describe the biochemistry of melatonin along with its therapeutic potential in various diseases of humans., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

In recent years, the study of interleukins (ILs), crucial cytokines involved in immune response and inflammation, has garnered significant attention within the sphere of cardiovascular diseases (CVDs). The research has provided insights into the involvement of ILs in diverse CVDs, including arrhythmias, myocardial infarction, atherosclerosis, and heart failure (HF). ILs have emerged as promising therapeutic targets for drug interventions through their involvement in disease development and progression. This comprehensive review provides a detailed overview of ILs, elucidating their functions within the immune system and offering insights into their specific contributions to various CVDs. Moreover, the article delves into the examination of current and potential drug therapies that selectively target ILs in the management of CVDs, presenting a comprehensive analysis of the advantages and disadvantages associated with these therapeutic approaches. A comprehensive literature review was conducted to investigate the involvement of ILs in CVDs. The relevant articles were searched on PubMed, PubMed Central, Medline, Cochrane, Google Scholar, and ScienceDirect databases. The search encompassed articles published from these databases' inception until July 12, 2023. We first examine generalized aspects of ILs, particularly CVDs. Then, we shift focus towards examining the direct impact of ILs on cardiac cells and tissue; on the immune system and inflammation; endothelial cells and vascular function; and finally, their interactions with other signaling pathways and molecules. Then, we discuss the molecular mechanisms of various ILs. Sequentially, we delve into a comprehensive analysis of the individualized role of each distinct IL in diverse CVDs, examining their specific contributions. Finally, we explore the potential for targeted drug therapy to modulate IL activity, aiming to enhance outcomes for patients burdened with CVD. The objective is the identification of gaps in current knowledge and highlight areas that require further investigation within the context of cardiovascular medicine. Through deepening our comprehension of the intricate involvement of ILs in CVDs and harnessing their potential for targeted drug therapy, novel treatment strategies can be devised, leading to improved patient outcomes in cardiovascular medicine., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abubakar et al.)

Revolutionary advancements in regenerative medicine have brought stem cell therapy to the forefront, offering promising prospects for the regeneration of ischemic cardiac tissue. Yet, its full efficacy, safety, and role in treating ischemic heart disease (IHD) remain limited. This literature review explores the intricate mechanisms underlying stem cell therapy. Furthermore, we unravel the innovative approaches employed to bolster stem cell survival, enhance differentiation, and seamlessly integrate them within the ischemic cardiac tissue microenvironment. Our comprehensive analysis uncovers how stem cells enhance cell survival, promote angiogenesis, and modulate the immune response. Stem cell therapy harnesses a multifaceted mode of action, encompassing paracrine effects and direct cell replacement. As our review progresses, we underscore the imperative for standardized protocols, comprehensive preclinical and clinical studies, and careful regulatory considerations. Lastly, we explore the integration of tissue engineering and genetic modifications, envisioning a future where stem cell therapy reigns supreme in regenerative medicine., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abubakar et al.)

A global outbreak of coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), mounted a substantial threat to public health worldwide. It initially emerged as a mere outbreak in Wuhan, China, in December 2019 and quickly engulfed the entire world, evolving into a global pandemic, consuming millions of lives and leaving a catastrophic effect on our lives in ways unimaginable. The entire healthcare system was significantly impacted and HIV healthcare was not spared. In this article, we reviewed the effect of HIV on COVID-19 disease and the ramifications of the recent COVID-19 pandemic over HIV management strategies. Our review highlights that contrary to the instinctive belief that HIV should render patients susceptible to COVID-19 infection, the studies depicted mixed results, although comorbidities and other confounders greatly affected the results. Few studies showed a higher rate of in-hospital mortality due to COVID-19 among HIV patients; however, the use of antiretroviral therapy had no consequential effect. COVID-19 vaccination was deemed safe among HIV patients in general. The recent pandemic can destabilize the HIV epidemic control as it hugely impacted access to care and preventive services and led to a marked reduction in HIV testing. The collision of these two disastrous pandemics warrants the need to materialize rigorous epidemiological measures and health policies, but most importantly, brisk research in prevention strategies to mitigate the combined burden of the two viruses and to battle similar future pandemics., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Abbasi et al.)

Objectives: This study aimed to evaluate hemodynamic correlates of inducible blood pressure (BP) pulsatility with exercise in heart failure with preserved ejection fraction (HFpEF), to identify relationships to outcomes, and to compare this with heart failure with reduced ejection fraction (HFrEF)., Background: In HFpEF, determinants and consequences of exercise BP pulsatility are not well understood., Methods: We measured exercise BP in 146 patients with HFpEF who underwent invasive cardiopulmonary exercise testing. Pulsatile BP was evaluated as proportionate pulse pressure (PrPP), the ratio of pulse pressure to systolic pressure. We measured pulmonary arterial catheter pressures, Fick cardiac output, respiratory gas exchange, and arterial stiffness. We correlated BP changes to central hemodynamics and cardiovascular outcome (nonelective cardiovascular hospitalization) and compared findings with 57 patients with HFrEF from the same referral population., Results: In HFpEF, only age (standardized beta = 0.593; P < 0.001), exercise stroke volume (standardized beta = 0.349; P < 0.001), and baseline arterial stiffness (standardized beta = 0.182; P = 0.02) were significant predictors of peak exercise PrPP in multivariable analysis (R = 0.661). In HFpEF, lower PrPP was associated with lower risk of cardiovascular events, despite adjustment for confounders (HR:0.53 for PrPP below median; 95% CI: 0.28-0.98; P = 0.043). In HFrEF, lower exercise PrPP was not associated with arterial stiffness but was associated with lower peak exercise stroke volume (P = 0.013) and higher risk of adverse cardiovascular outcomes (P = 0.004)., Conclusions: In HFpEF, greater inducible BP pulsatility measured using exercise PrPP reflects greater arterial stiffness and higher risk of adverse cardiovascular outcomes, in contrast to HFrEF where inducible exercise BP pulsatility relates to stroke volume reserve and favorable outcome., Competing Interests: Funding Support and Author Disclosures Dr Namasivayam is supported by a Clinical and Research Fellowship from the Division of Cardiology, Massachusetts General Hospital, Harvard Medical School; and is a recipient of the St. Vincent’s Clinic Travelling Fellowship Award. Dr Lewis is supported by the American Heart Association Award 15GPSGC24800006 and by the National Heart, Lung and Blood Institute Awards R01-HL 131029 and R01-HL151841. Dr Nayor is supported by National Institutes of Health/National Heart, Lung, and Blood Institute K23-HL138260. Dr Ho is supported by National Institutes of Health/National Heart, Lung, and Blood Institute R01-HL134893 and R01-HL140224. Dr Malhotra is supported by Transformation Project Award 18TPA34230025 from the American Heart Association and grant R01-HL142809 from the National Heart, Lung, and Blood Institute. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022. Published by Elsevier Inc.)

Objective: Ginger ( Zingiber officinale Roscoe) is considered to be one of the most commonly consumed dietary condiments of the world. The present study was designed to explicate the protective role of zingerone; an active ingredient of ginger in complete Freund's adjuvant (FCA)-immunized arthritic rats., Methods: 24 Wistar rats were divided into 4 groups with 6 rats each. Group I as control followed by group II, III and IV were treated with single intradermal injection of FCA (0.1 ml = 100 µg) to induce rheumatoid arthritis. Group III and IV were also administered with zingerone orally at 25 mg/kg b.w for 3 weeks at two different time points., Results: Adjuvant-treated rats exhibited a significant increase in lipid peroxidation and a reduction in the enzymatic antioxidants such as SOD, catalase and GPx, in the liver and joint tissues. Moreover, FCA inoculation resulted in the increase in levels of NF-κB, TGF-β, TNF-α, IL-1β, IL-6 and Hs-CRP and a decrease in IL-10 levels. Zingerone significantly reduced the levels of NF-κB, TGF-β, TNF-α, IL-1β, IL-6 and Hs-CRP and markedly increased IL-10 levels. Levels of antioxidant enzymes were also restored by zingerone treatment., Discussion: Oral administration of zingerone ameliorated inflammatory outburst and decreased oxidative stress, suggesting its role in the prevention of rheumatoid arthritis. Further mechanistic insights are necessary to study the exact mechanism involved.

Background: Fractures in and around the hip are a major concern in young as well as the elderly. Ultrasound-guided (USG) peripheral nerve blocks help in early surgical fixation of these fractures by providing perioperative pain relief as well as early mobilization resulting in reduced morbidity and mortality., Aims: This study aims to compare the efficacy of USG pericapsular nerve group (PENG) block versus fascia iliaca compartment (FIC) block., Setting and Design: Prospective, randomized, double-blind, controlled study., Materials and Methods: Twenty-four patients above 18 years of age with hip fracture belonging to the American Society of Anaesthesiologists physical status Classes I and II scheduled for hip surgery were randomly allocated into two groups. Group 1(PENG block) received USG-guided PENG block and Group 2 (FIC block) received USG guided FIC block for postoperative pain relief. Postoperative pain relief (at rest) was evaluated by Numeric Rating Scale score from 20 th min and at regular interval for 24 h. The total analgesic consumption in the first 24 h was also noted., Statistical Analysis Used: Data were analyzed by using nonparametric test and Chi-square test. Hemodynamic variables and pain scores were analyzed using analysis of variance for two groups and independent t -test was used for comparison between two groups., Results: Postoperative NRS score was higher in FIC block than PENG block which was statistically significant at 1 h ( P = 0.035) and at 4 h ( P = 0.001). The first requirement of analgesic was significantly late in PENG block group (8.17 ± 3.129) as compared to FIC block group (4.00 ± 1.477)., Conclusions: PENG block provides better postoperative analgesia, with reduced requirement of rescue analgesics in 24 h as compared to FIC block in patients undergoing surgeries for hip fracture under spinal anesthesia., Competing Interests: There are no conflicts of interest., (Copyright: © 2022 Anesthesia: Essays and Researches.)

Background: Obesity has multifactorial effects on lung function and exercise capacity. The contributions of obesity-related inflammatory pathways to alterations in lung function remain unclear., Research Question: To examine the association of obesity-related inflammatory pathways with pulmonary function, exercise capacity, and pulmonary-specific contributors to exercise intolerance., Method: We examined 695 patients who underwent cardiopulmonary exercise testing (CPET) with invasive hemodynamic monitoring at Massachusetts General Hospital between December 2006-June 2017. We investigated the association of adiponectin, leptin, resistin, IL-6, CRP, and insulin resistance (HOMA-IR) with pulmonary function and exercise parameters using multivariable linear regression., Results: Obesity-related inflammatory pathways were associated with worse lung function. Specifically, higher CRP, IL-6, and HOMA-IR were associated with lower percent predicted FEV 1 and FVC with a preserved FEV 1 /FVC ratio suggesting a restrictive physiology pattern (P ≤ 0.001 for all). For example, a 1-SD higher natural-logged CRP level was associated with a nearly 5% lower percent predicted FEV 1 and FVC (beta -4.8, s.e. 0.9 for FEV1; beta -4.9, s.e. 0.8 for FVC; P < 0.0001 for both). Obesity-related inflammatory pathways were associated with worse pulmonary vascular distensibility (adiponectin, IL-6, and CRP, P < 0.05 for all), as well as lower pulmonary artery compliance (IL-6 and CRP, P ≤ 0.01 for both)., Interpretation: Our findings highlight the importance of obesity-related inflammatory pathways including inflammation and insulin resistance on pulmonary spirometry and pulmonary vascular function. Specifically, systemic inflammation as ascertained by CRP, IL-6 and insulin resistance are associated with restrictive pulmonary physiology independent of BMI. In addition, inflammatory markers were associated with lower exercise capacity and pulmonary vascular dysfunction., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Exercise testing plays an important role in evaluating heart failure prognosis and selecting patients for advanced therapeutic interventions. However, concern for severe acute respiratory syndrome novel coronavirus-2 transmission during exercise testing has markedly curtailed performance of exercise testing during the novel coronavirus disease-2019 pandemic., Methods and Results: To examine the feasibility to conducting exercise testing with an in-line filter, 2 healthy volunteer subjects each completed 2 incremental exercise tests, one with discrete stages of increasing resistance and one with a continuous ramp. Each subject performed 1 test with an electrostatic filter in-line with the system measuring gas exchange and air flow, and 1 test without the filter in place. Oxygen uptake and minute ventilation were highly consistent when evaluated with and without use of an electrostatic filter with a >99.9% viral efficiency., Conclusions: Deployment of a commercially available in-line electrostatic viral filter during cardiopulmonary exercise testing is feasible and provides consistent data compared with testing without a filter., (Copyright © 2020. Published by Elsevier Inc.)

Background and Aims: The ultrasound-guided infraclavicular brachial plexus block (USG ICBPB) is a popular technique for forearm surgeries distal to the elbow. Our study details the ultrasound (US) characteristics of this block and the structures encountered by the needle in four approaches to the infraclavicular area - lateral infraclavicular (LICF), costoclavicular medial to lateral (CML) and lateral to medial (CLM) and retroclavicular (R) by anatomical dissection., Methods: USG ICBPB was performed in 10 cadavers-5 on the right side and 5 on the left side by each of four approaches and with an 18 gauge Tuohy needle kept in situ , and US characteristics were noted. Anatomical dissection was done and important structures were described in detail., Results: Needle tip and shaft visibility were least with LICF approach and best in R approach. Needle angle correlated with chest and neck circumference in LICF and CML groups. During dissection, in all approaches, neurovascular structures have been observed in the near vicinity of the needle, especially the thoracoacromial artery (TAA) or its branches. In the R approach, the 'blind spot' behind the clavicle is an area where neurovascular structures were present., Conclusion: The R approach gives better visibility of needle shaft beyond the clavicle, but the clavicle acts as a 'blind-spot' for the US beam obliterating important neurovascular structures. The various neurovascular structures the needle traverses or in its immediate vicinity, do not necessarily make the CML, CLM or R approach any better than the LICF approach., Competing Interests: There are no conflicts of interest., (Copyright: © 2020 Indian Journal of Anaesthesia.)

Ventriculitis after meningitis is a serious complication in the neonatal age group. The role of intraventricular antibiotics in treatment is controversial. We present five such cases which were refractory to conventional intravenous antibiotic therapy, had persistent features of ventriculitis and in whom raised intracranial pressure (ICP) necessitated insertion of an external ventricular drain (EVD). Three of the five infants required intraventricular antibiotics but also developed EVD-related complications. Early diagnosis of ventriculitis and treatment is necessary to avoid a fatal outcome. Intravenous antibiotics are the treatment of choice, but intraventricular therapy may be considered in refractory cases. As the incidence of EVD-associated ventriculitis is high, proper care of EVDs and their early removal is mandatory.

Background: Fat embolism syndrome (FES) following major orthopedic injuries and surgeries is a well-known phenomenon where acute depression of right ventricular (RV) systolic function is a potential possibility. Clinical presentation of FES may vary from mild self-limiting nature to severe life-threatening multiorgan dysfunction syndrome with pulmonary manifestations being most common., Aims: This study was aimed to know whether perioperative assessment of RV function by measuring tricuspid annular plane systolic excursion (TAPSE) with point-of-care transthoracic echocardiogram will identify patients at risk of developing FES and its sequelae., Settings and Design: This was a prospective observational study., Materials and Methods: This study was carried out in 142 patients with femur fractures posted for correction surgeries of both genders who require intramedullary (IM) reaming. TAPSE was recorded four times perioperatively. Time taken for IM reaming was also recorded., Statistical Analysis Used: Recorded data were analyzed using professional statistics package Epi Info 7.0 version for Windows. Descriptive data were represented as mean ± standard deviation for numeric variables, percentages, and proportions for categorical variables. Repeated-measure ANOVA was applied to assess the changes in TAPSE from baseline to immediate postoperative, after 6-h postoperative, and after 24-h postoperatively. Pearson's correlation was utilized to be applied to assess the relationship between TAPSE and other numerical variables., Results: All four readings of TAPSE were well above 17 mm (mean of 19.06, 19.05, 19.04, and 19.04, respectively). Mean reaming time was found to be 6.92 min. None of the patients developed any postoperative pulmonary complications., Conclusion: Assessment of RV function can be done with relative ease using TAPSE as a noninvasive method without any complications. Reaming time not exceeding 12 min did not produce any changes in RV function as measured by TAPSE as well as any postoperative pulmonary complications., Competing Interests: There are no conflicts of interest.

Purpose: G protein-coupled receptors (GPCRs) represent the largest family of druggable targets in human genome. Although several GPCRs can cross-talk with the human epidermal growth factor receptors (HERs), the expression and function of most GPCRs remain unknown in HER2+ breast cancer (BC). In this study, we aimed to evaluate gene expression of GPCRs in tumorigenic or anti-HER2 drug-resistant cells and to understand the potential role of candidate GPCRs in HER2+ BC., Methods: Gene expression of 352 GPCRs was profiled in Aldeflur+ tumorigenic versus Aldeflur- population and anti-HER2 therapy-resistant derivatives versus parental cells of HER2+ BT474 cells. The GPCR candidates were confirmed in 7 additional HER2+ BC cell line models and publicly available patient dataset. Anchorage-dependent and anchorage-independent cell growth, mammosphere formation, and migration/invasion were evaluated upon GPR110 knockdown by siRNA in BT474 and SKBR3 parental and lapatinib+ trastuzumab-resistant (LTR) cells., Results: Adhesion and class A GPCRs were overexpressed in Aldeflur+ and anti-HER2 therapy-resistant population of BT474 cells, respectively. GPR110 was the only GPCR overexpressed in Aldeflur+ and anti-HER2 therapy-resistant population in BT474, SKBR3, HCC1569, MDA-MB-361, AU565, and/or HCC202 cells and in HER2+ BC subtype in patient tumors. Using BT474 and SKBR3 parental and LTR cells, we found that GPR110 knockdown significantly reduced anchorage-dependent/independent cell growth as well as migration/invasion of parental and LTR cells and mammosphere formation in LTR derivatives and not in parental cells., Conclusion: Our data suggest a potential role of GPR110 in tumorigenicity and in tumor cell dissemination in HER2+ BC.

Context: Optimization and providing excellent quality of postoperative analgesia after total abdominal hysterectomy is a determinant factor of better clinical outcome, increases patient satisfaction, and allows early mobilization of the patient., Aims: The aim of this study is to compare the postoperative analgesic efficacy of wound site infiltration (WSI) and ultrasound-guided transversus abdominis plane block (TAPB) with 0.5% ropivacaine in lower abdominal surgeries under spinal anesthesia., Settings and Design: This was a randomized controlled study., Subjects and Methods: One hundred and ten patients undergoing lower abdominal surgeries were randomly allocated to two groups (WSI and TAP) of 55 patients in each. At the end of the surgical procedure, 2.5 mg/kg of the drug ropivacaine 0.5% was administered by an anesthesiologist through either of the routes of study. Visual analog score (VAS) assessment was done at every 30 min, for 1½ h, every 2 for 24 h postoperatively. Injection diclofenac sodium 75 mg intramuscularly was given whenever VAS was >3 as rescue analgesic., Statistical Analysis Used: Epi Info 7.0 version software for Windows was used. All analyses were performed using Kolmogorov-Smirnov test. Mann-Whitney test was applied to detect the difference between the two groups. P < 0.05 was considered statistically significant., Results: Postoperative VAS scores in Group TAP were significantly reduced at 30 min, 1 st h, 1 h 30 min, 2, 4, 6, 8, 10, 12, 18, and 24 h ( P < 0.001). The total doses of rescue analgesics administered were also low in the Group TAP (1.41 ± 0.538) with P < 0.0001 in comparison to Group WSI (2.24 ± 0.637) with P < 0.001., Conclusions: The quality of analgesia along with lesser rescue analgesic requirement and their side effects makes the TAPB, a good and safer option for lower abdominal gynecological surgeries. Both WSI and USG TAPB are effective in providing postoperative analgesia as a part of multimodal analgesia in lower abdominal surgeries. However, in our study the quality of analgesia along with lesser rescue analgesic requirement and their side effects makes the TAPB, a good and safer option for lower abdominal gynecological surgeries., Competing Interests: There are no conflicts of interest.

Surgery risk assessment is an effective tool for physicians to manage the treatment of patients, but most current research projects fall short in providing a comprehensive platform to evaluate the patients' surgery risk in terms of different complications. The recent evolution of big data analysis techniques makes it possible to develop a real-time platform to dynamically analyze the surgery risk from large-scale patients information. In this paper, we propose the Intelligent Perioperative System (IPS), a real-time system that assesses the risk of postoperative complications (PC) and dynamically interacts with physicians to improve the predictive results. In order to process large volume patients data in real-time, we design the system by integrating several big data computing and storage frameworks with the high through-output streaming data processing components. We also implement a system prototype along with the visualization results to show the feasibility of system design.

Bipolar disorder, also known as manic depression, is a brain disorder that affects the brain structure of a patient. It results in extreme mood swings, severe states of depression, and overexcitement simultaneously. It is estimated that roughly 3% of the population of the United States (about 5.3 million adults) suffers from bipolar disorder. Recent research efforts like the Twin studies have demonstrated a high heritability factor for the disorder, making genomics a viable alternative for detecting and treating bipolar disorder, in addition to the conventional lengthy and costly postsymptom clinical diagnosis. Motivated by this study, leveraging several emerging deep learning algorithms, we design an end-to-end deep learning architecture (called DeepBipolar) to predict bipolar disorder based on limited genomic data. DeepBipolar adopts the Deep Convolutional Neural Network (DCNN) architecture that automatically extracts features from genotype information to predict the bipolar phenotype. We participated in the Critical Assessment of Genome Interpretation (CAGI) bipolar disorder challenge and DeepBipolar was considered the most successful by the independent assessor. In this work, we thoroughly evaluate the performance of DeepBipolar and analyze the type of signals we believe could have affected the classifier in distinguishing the case samples from the control set., (© 2017 Wiley Periodicals, Inc.)

Precision medicine aims to predict a patient's disease risk and best therapeutic options by using that individual's genetic sequencing data. The Critical Assessment of Genome Interpretation (CAGI) is a community experiment consisting of genotype-phenotype prediction challenges; participants build models, undergo assessment, and share key findings. For CAGI 4, three challenges involved using exome-sequencing data: Crohn's disease, bipolar disorder, and warfarin dosing. Previous CAGI challenges included prior versions of the Crohn's disease challenge. Here, we discuss the range of techniques used for phenotype prediction as well as the methods used for assessing predictive models. Additionally, we outline some of the difficulties associated with making predictions and evaluating them. The lessons learned from the exome challenges can be applied to both research and clinical efforts to improve phenotype prediction from genotype. In addition, these challenges serve as a vehicle for sharing clinical and research exome data in a secure manner with scientists who have a broad range of expertise, contributing to a collaborative effort to advance our understanding of genotype-phenotype relationships., (© 2017 Wiley Periodicals, Inc.)

Competing Interests: There are no conflicts of interest.

Background: Breakdown of the mucosal barrier resulting in mucositis is a common adverse event in patients with cancer receiving chemotherapy and radiation. Many studies have evaluated the use of oral glutamine to prevent mucositis in these settings, but current guidelines make no recommendations with regard to its use. Our objective was to systematically review the evidence for the use of oral glutamine in preventing mucositis in adult patients with cancer undergoing chemotherapy and/or radiation., Materials and Methods: A systematic search of English-language literature was done via MEDLINE using the search terms glutamine, cancer, and mucositis or esophagitis or stomatitis. Fifteen studies conducted in adult patients with cancer receiving chemotherapy and/or radiation comparing single-agent oral glutamine with control were identified., Results: Oral glutamine was shown to be effective in 11 of the 15 studies included in the systematic review. It significantly reduced the incidence of grade 2, 3, or 4 mucositis and/or reduced weight loss as well as the duration, time of onset, and/or maximum grade of mucositis. The most common dosing regimen was 30 g/d in 3 divided doses, with other regimens ranging from 7.5-24 g/d. Rates of nausea, vomiting, dry mouth, and anorexia were similar in the glutamine and control groups., Conclusion: In summary, the favorable efficacy and low toxicity of oral glutamine observed in clinical trials we reviewed provide a strong rationale for large randomized placebo-controlled studies to further evaluate its efficacy in preventing mucositis in patients with cancer receiving chemotherapy and/or radiation., (© 2015 American Society for Parenteral and Enteral Nutrition.)

Background: A sustained and effective oropharyngeal sealing with supraglottic airway (SGA) is required to maintain the ventilation during laparoscopic gynecological surgery in the Trendelenburg position. This study was conducted with I-gel™ and ProSeal LMA™, two prototype SGA devices with a gastric access., Materials and Methods: We enrolled 60 American Society of Anesthesiologists physical status I and II patients and randomized to either I-gel or ProSeal LMA (PLMA) group. After induction of anesthesia using a standardized protocol, one of the SGA devices was inserted. The primary objective of this study was to compare the oropharyngeal leak (sealing) pressure of I-gel™ and ProSeal LMA™ after pneumoperitoneum and Trendelenberg position. The secondary objectives were to compare ease of insertion, cuff position as assessed by the fiberoptic view of the glottis, adequacy of ventilation and incidence of complication., Results: The baseline (before pneumoperitoneum) oropharyngeal leak pressure of I-gel was less than the PLMA (mean (standard deviation [SD]) 24 (4) vs. 29 (4) cmH2O, respectively; P < 0.001). After pneumoperitoneum, the leak airway pressure in I-gel group was significantly less than that of PLMA group (mean [SD] 27 (3) vs. 34.0 (4) cmH2O, respectively; P < 0.001). Peak airway pressure was increased after pneumoperitoneum compared to baseline in both the groups. However, end-tidal carbon dioxide was maintained within normal limits. The insertion parameters, fiberoptic view of the glottis, fiberoptic view of the drain tube, and complications were comparable between the groups., Conclusion: Both I-gel and PLMA are effective for ventilation in gynecological laparoscopic surgeries. However, PLMA provides better sealing as compared to I-gel.

A 52-year-old man was presented with discomfort in lower abdomen and irritative voiding symptoms. Computed tomography showed a well circumscribed mass with calcification in front of bladder compressing the bladder diagnosed as leiomyoma with calcifications, probably araising from rectum. Surgery revealed a giant peritoneal loose body measuring 6cm in diameter. After the removal of peritoneal loose body patient was relieved of symptoms. Peritoneal loose bodies are usually small and are found incidentally at surgery. Giant peritoneal loose bodies are rare. A comprehensive review of literature is presented.

A combined experimental and theoretical approach establishes the long-lived nature of protein adsorption on surfaces coated with chemically grafted macromolecules. Specifically, we monitor the time dependence of adsorption of lysozyme on surfaces comprising polymer assemblies made of poly(2-hydroxyethyl methacrylate) brushes grafted onto flat silica surfaces such that they produce patterns featuring orthogonal and gradual variation of the chain length (N) and grafting density (σ). We show that in the kinetically controlled regime, the amount of adsorbed protein scales universally with the product σN, while at equilibrium the amount of adsorbed protein is governed solely by σ. Surprisingly, for moderate concentrations of protein in solution, adsorption takes more than 72 h to reach an equilibrium, or steady state. Our experimental findings are corroborated with predictions using molecular theory that provides further insight into the protein adsorption phenomenon. The theory predicts that the universal behavior observed experimentally should be applicable to polymers in poor and theta solvents and to a limited extent also to good solvent conditions. Our combined experimental and theoretical findings reveal that protein adsorption is a long-lived phenomenon, much longer than generally assumed. Our studies confirm the previously predicted important differences in behavior for the kinetic versus thermodynamic control of protein adsorption., (© 2011 American Chemical Society)

This feature article describes the progress realized over the past half century in the field of surface-bound gradient structures created on or from soft materials (oligomers and/or polymers), or those enabling the study of the behavior of soft materials. By highlighting our work in the field and accounting for the contribution of other groups, we emphasize the exceptional versatility of gradient assemblies in facilitating fast screening of physicochemical phenomena, acting as "recording media" for monitoring a process, and playing a key role in the design and fabrication of surface-bound molecular and macromolecular motors capable of directing a transport phenomenon.