Ovarian Cystic Lymphangioma.

Lymphangioma are benign, slow-growing and rare lymphatic tumors, which may emerge at any location in the body with ovary being a very rare location. Axillary region and neck are the most common sites, while retroperitoneum and mesentery account for <1%. We present a case of a young female of 33 years who had symptomatic pelvic mass and was presented with a complaint of lower abdominal pain of six-month duration and weight loss. Investigation revealed an oval-shaped complex cystic density lesion in the right adnexal region, which was likely neoplastic. Elective laparotomy with right ovarian cystectomy was performed. Histopathological examination revealed ovarian lymphangioma.

pH-dependent Synthesis and Interactions of Fluorescent L-Histidine Capped Copper Nanoclusters with Metal Ions.

In this work, L-Histidine-protected copper nanoclusters synthesized by changing the pH levels of precursor solution have been shown to display different emission wavelengths and intensities. As determined by mass spectrometry, nanoclusters Cu3L2 synthesized at acidic pH have 3 atoms in their core and emit in the greenish-yellow region, and nanoclusters Cu2L2, synthesized in the basic conditions have 2 atoms in their core and emit in the blue-green region. They are expected to have coordination through the carboxylate group and nitrogen of the imidazole ring of histidine ligand, respectively. Metal ions Mg2+, Mn2+, Zn2+, and Pb2+ selectively enhance the interaction between carboxylate - copper metal core and increase the emission intensity of Cu3L2. These metal ions weaken the interaction between imidazole nitrogen and copper metal core and quench the emission intensity of Cu2L2. As synthesized, nanoclusters exhibit good water solubility and photostability, they can act as fluorescent probes to sense the metal ions, therefore, they were utilized for the optical sensing of the mentioned metal ions. Fluorescent nanoclusters were found to sense even a very low concentration of metal ions with a limit of detection (3 σ/slope) in nanomolar range.

Perspective of artificial intelligence in healthcare data management: A journey towards precision medicine.

Mounting evidence has highlighted the implementation of big data handling and management in the healthcare industry to improve the clinical services. Various private and public companies have generated, stored, and analyzed different types of big healthcare data, such as omics data, clinical data, electronic health records, personal health records, and sensing data with the aim to move in the direction of precision medicine. Additionally, with the advancement in technologies, researchers are curious to extract the potential involvement of artificial intelligence and machine learning on big healthcare data to enhance the quality of patient's lives. However, seeking solutions from big healthcare data requires proper management, storage, and analysis, which imposes hinderances associated with big data handling. Herein, we briefly discuss the implication of big data handling and the role of artificial intelligence in precision medicine. Further, we also highlighted the potential of artificial intelligence in integrating and analyzing the big data that offer personalized treatment. In addition, we briefly discuss the applications of artificial intelligence in personalized treatment, especially in neurological diseases. Lastly, we discuss the challenges and limitations imposed by artificial intelligence in big data management and analysis to hinder precision medicine.

The evolving role of JAK inhibitors in the treatment of inflammatory bowel disease.

INTRODUCTION: Janus Kinase inhibitors (JAKi) are a new class of oral therapies for the treatment of moderate-severe ulcerative colitis with additional potential for the treatment of moderate-severe Crohn's disease. In contrast to biologic therapies JAKi provide the opportunity for non-immunogenic once or twice daily oral therapies. AREAS COVERED: Janus Kinase inhibitors for the treatment of ulcerative colitis and Crohn's disease based on mechanism of action, pharmacokinetics, clinical trial and real-world data regarding safety and efficacy; focusing on regulatory approvals in the U.S. and Europe. EXPERT OPINION: Janus Kinase inhibitors are considered among the 'advanced therapies' for IBD and are approved for the treatment of moderate to severe ulcerative colitis in adults with pending approvals for Crohn's disease in the U.S. JAKi offer non-immunogenic, oral options for patient not responding to other conventional agents but, have been 'restricted' by the FDA to patients with inadequate response to TNF blockers. JAKi offer rapidly acting oral alternatives to biologic agents for moderate-severe ulcerative colitis where the risks of cardiovascular and thrombotic events noted in rheumatoid arthritis have not been observed in IBD clinical trials. Nevertheless, monitoring of infections (primarily herpes zoster) and risk factors for cardiovascular and thrombotic complications is appropriate.

Towards Green Synthesis of Fluorescent Metal Nanoclusters.

In the modern development of nanoscience and nanotechnology, metal nanoclusters have emerged as a foremost category of nanomaterials exhibiting remarkable biocompatibility and photo-stability having dramatically distinctive optical, electronic, and chemical properties. This review focuses on synthesizing fluorescent metal nanoclusters in a greener way to make them suitable for biological imaging and drug delivery application. The green methodology is the desired route for sustainable chemical production and should be utilized for any form of chemical synthesis including nanomaterials. It aims to eliminate harmful waste, uses non-toxic solvents, and employs energy-efficient processes for the synthesis. This article provides an overview of conventional synthesis methods, including stabilizing nanoclusters by small organic molecules in organic solvents. Then we focus on the improvement of properties, applications of green synthesized metal nanoclusters, challenges involved, and further advancement required in the direction of green synthesis of MNCs. There are plenty of problems for scientists to solve to make nanoclusters suitable for bio-applications, chemical sensing, and catalysis synthesized by green methods. Using bio-compatible and electron-rich ligands, understanding ligand-metal interfacial interactions, employing more energy-efficient processes, and utilizing bio-inspired templates for synthesis are some immediate problems worth solving in this field that requires continued efforts and interdisciplinary knowledge and collaboration.

Harnessing Innate Immunity to Treat Mycobacterium tuberculosis Infections: Heat-Killed Caulobacter crescentus as a Novel Biotherapeutic.

Tuberculosis, caused by Mycobacterium tuberculosis (Mtb), is a serious and devastating infectious disease worldwide. Approximately a quarter of the world population harbors latent Mtb infection without pathological consequences. Exposure of immunocompetent healthy individuals with Mtb does not result in active disease in more than 90% individuals, suggesting a defining role of host immunity to prevent and/or clear early infection. However, innate immune stimulation strategies have been relatively underexplored for the treatment of tuberculosis. In this study, we used cell culture and mouse models to examine the role of a heat-killed form of a non-pathogenic microbe, Caulobacter crescentus (HKCC), in inducing innate immunity and limiting Mtb infection. We also examined the added benefits of a distinct chemo-immunotherapeutic strategy that incorporates concurrent treatments with low doses of a first-line drug isoniazid and HKCC. This therapeutic approach resulted in highly significant reductions in disseminated Mtb in the lungs, liver, and spleen of mice compared to either agent alone. Our studies demonstrate the potential of a novel innate immunotherapeutic strategy with or without antimycobacterial drugs in controlling Mtb infection in mice and open new avenues for the treatment of tuberculosis in humans.

Anaplastic Intraventricular Meningioma with Rhabdoid Features: An Unusual Tumor with Usual Clinical Presentation.

Meningiomas are tumors arising from leptomeninges. Malignant counterpart of them is known as anaplastic meningioma which are WHO grade III tumors. Intraventricular location of these tumors is rare and is clinic-radiologically challenging. Histopathology and immunohistochemistry are confirmatory. We present case of a 27-year-old girl, who presented with usual symptoms of intraventricular mass in emergency. After shunt surgery, clinical diagnosis of ependymoma was formed with differential of high-grade glioma. Squash tissue was difficult to crush displaying tight clusters of spindle cells with necrosis in background. Definitive histology revealed high grade spindle cell neoplasm disposed in sheets with brisk and atypical mitosis. Only focal whorling pattern was seen. Large cells with eccentric cytoplasm, reminiscent of rhabdoid cells were also seen. Immunohistochemistry was positive for vimentin and EMA, negative for GFAP. Final diagnosis of Anaplastic meningioma was dispatched. The histological pattern of the present case, young age of presentation and presence of Rhabdoid cells make it unusual. Though rare but intraventricular meningiomas must also be kept in clinical radiological differentials apart from the usual ependymoma at this location.

Yield, cell composition, and function of islets isolated from different ages of neonatal pigs.

The yield, cell composition, and function of islets isolated from various ages of neonatal pigs were characterized using in vitro and in vivo experimental models. Islets from 7- and 10-day-old pigs showed significantly better function both in vitro and in vivo compared to islets from 3- and 5-day-old pigs however, the islet yield from 10-day-old pigs were significantly less than those obtained from the other pigs. Since islets from 3-day-old pigs were used in our previous studies and islets from 7-day-old pigs reversed diabetes more efficiently than islets from other groups, we further evaluated the function of these islets post-transplantation. B6 rag-/- mouse recipients of various numbers of islets from 7-day-old pigs achieved normoglycemia faster and showed significantly improved response to glucose challenge compared to the recipients of the same numbers of islets from 3-day-old pigs. These results are in line with the findings that islets from 7-day-old pigs showed reduced voltage-dependent K+ (Kv) channel activity and their ability to recover from post-hypoxia/reoxygenation stress. Despite more resident immune cells and immunogenic characteristics detected in islets from 7-day-old pigs compared to islets from 3-day-old pigs, the combination of anti-LFA-1 and anti-CD154 monoclonal antibodies are equally effective at preventing the rejection of islets from both age groups of pigs. Collectively, these results suggest that islets from various ages of neonatal pigs vary in yield, cellular composition, and function. Such parameters may be considered when defining the optimal pancreas donor for islet xenotransplantation studies.

Cyanidin-3-O-Glucoside improves the viability of human islet cells treated with amylin or Aß1-42 in vitro.

Islet transplantation is being considered as an alternative treatment for type 1 diabetes. Despite recent progress, transplant recipients continue to experience progressive loss of insulin independence. Cyanidin-3-O-Glucoside (C3G) has shown to be protective against damage that may lead to post-transplant islet loss. In this study, human islets cultured with or without C3G were treated with human amylin, Aß1-42, H2O2, or rapamycin to mimic stresses encountered in the post-transplant environment. Samples of these islets were collected and assayed to determine C3G's effect on cell viability and function, reactive oxygen species (ROS), oxidative stress, amyloid formation, and the presence of inflammatory as well as autophagic markers. C3G treatment of human islets exposed to either amylin or Aß1-42 increased cell viability (p<0.01) and inhibited amyloid formation (p<0.01). A reduction in ROS and an increase in HO-1 gene expression as well as in vitro islet function were also observed in C3G-treated islets exposed to amylin or Aß1-42, although not significantly. Additionally, treatment with C3G resulted in a significant reduction in the protein expression of inflammatory markers IL-1ß and NLRP3 (p<0.01) as well as an increase in LC3 autophagic marker (p<0.05) in human islets treated with amylin, Aß1-42, rapamycin, or H2O2. Thus, C3G appears to have a multi-faceted protective effect on human islets in vitro, possibly through its anti-oxidant property and alteration of inflammatory as well as autophagic pathways.

Marker association study of yield attributing traits in common bean (Phaseolus vulgaris L.).

Common bean is gaining acceptance as one of the most valuable major food consumed worldwide owing to innumerable nutritional and therapeutic benefits. Comparatively less productivity in underdeveloped countries encouraged us to proceed for QTL mining of yield traits in common bean. Heretofore, multiple yield associated markers have been detected all over the world; even so, the present work is looked on as the first report on identification of novel/new potent markers by exploiting the germplasm of Northern India. A panel of one hundred and thirty five genotypes was used for morphological studies and based on preliminary molecular evaluation; a set of ninety six diverse common bean genotypes (core set) was selected for association analysis. Molecular data generated by a total of ninety eight microsatellite markers (53 genomic and 45 genic SSRs) revealed high estimation of polymorphism among the genotypes that were observed to be divided into two major sub-populations and varying levels of admixtures based on population structure analyses. By employing both MLM and GLM analysis approaches, we identified 46 and 16 significant marker-trait associations (p ≤ 0.005) respectively, few of which have already been reported and hence validate our results. PVBR213 marker was found to be strongly associated with days to bud initiation trait when analyzed with both the approaches. Phenotypic variation of identified significant markers ranged from 3.1% to 32.7% where PVBR87, PVBR213, X96999 and X57022 explain more than 30% of phenotypic variation for 100 seed weight, days to bud initiation, pods per plant and pod length traits respectively. These findings introduce highly informative markers to aid marker-assisted selection program in common bean for high yield performance along with good agronomic merit.

Early immune mechanisms of neonatal porcine islet xenograft rejection.

BACKGROUND: Neonatal pigs have the potential to provide an inexhaustible source of islets for the treatment of type 1 diabetes. However, the immunological barriers to islet xenotransplantation still need to be overcome. A better understanding of the xeno-specific immune responses that are involved in neonatal porcine islet (NPI) xenotransplant rejection will help to facilitate the identification of new targets for anti-rejection therapies, and thus enable more specific targeting of the immune cells and molecules involved. METHODS: In this study, we examined the early events of NPI xenograft rejection in the absence of autoimmunity using an immune-competent B6 mouse transplant model. Immune cells were identified by immunohistochemistry and immune molecules were identified by reverse transcription-PCR and flow cytometry assays. RESULTS: Our results demonstrated that early events in NPI xenograft rejection are characterized by initial infiltration of innate immune cells such as macrophages (M1) and neutrophils. CONCLUSIONS: Targeting these cells, which appear early in the rejection process, may provide an opportunity to abort the rejection process prior to activation of T cells. One strategy could be the blockade of chemotactic signals associated with preferential recruitment of immune cells into the graft site. Collectively, our studies demonstrated that early recruitment of immune cells into graft site is controlled by chemotactic activities and suggest a potential target to prevent the early infiltration of immune cells within the graft. Our findings in this study will have significance in improving NPI xenograft acceptance and induce long-term xenograft survival.

Heterologous Immunity between Adenoviruses and Hepatitis C Virus (HCV): Recombinant Adenovirus Vaccine Vectors Containing Antigens from Unrelated Pathogens Induce Cross-Reactive Immunity Against HCV Antigens.

Host immune responses play an important role in the outcome of infection with hepatitis C virus (HCV). They can lead to viral clearance and a positive outcome, or progression and severity of chronic disease. Extensive research in the past >25 years into understanding the immune responses against HCV have still resulted in many unanswered questions implicating a role for unknown factors and events. In our earlier studies, we made a surprising discovery that peptides derived from structural and non-structural proteins of HCV have substantial amino acid sequence homologies with various proteins of adenoviruses and that immunizing mice with a non-replicating, non-recombinant adenovirus vector leads to induction of a robust cross-reactive cellular and humoral response against various HCV antigens. In this work, we further demonstrate antibody cross-reactivity between Ad and HCV in vivo. We also extend this observation to show that recombinant adenoviruses containing antigens from unrelated pathogens also possess the ability to induce cross-reactive immune responses against HCV antigens along with the induction of transgene antigen-specific immunity. This cross-reactive immunity can (a) accommodate the making of dual-pathogen vaccines, (b) play an important role in the natural course of HCV infection and (c) provide a plausible answer to many unexplained questions regarding immunity to HCV.

Functionalized magnetic nanomaterials for rapid and effective adsorptive removal of fluoroquinolones: Comprehensive experimental cum computational investigations.

Alarming growth of pharmaceutical residues in aquatic environment has elevated concerns about their potential impact on human health. Taking cognizance of this, the present study is focussed on the coating of cobalt ferrite nanoparticles with different functionalities and to use them as adsorbents for pharmaceutical waste. The thickness of the coating was analysed using Small angle X-ray scattering technique. Thorough study of the isotherms and kinetics were performed suggesting monolayer adsorption and pseudo kinetic order model, respectively. To get an insight of the interactions liable for adsorption of fluoroquinolones over the functionalized magnetic nanoparticles computational studies were undertaken. The results demonstrated substantial evidence proposing remarkable potential of these nanostructures as adsorbents for different pollutants with an additional advantage of stability and facile recoverability with a view to treat wastewater.

MUC1 Mucin: A Putative Regulatory (Checkpoint) Molecule of T Cells.

T lymphocytes are at the center of inducing an effective adaptive immune response and maintaining homeostasis. T cell responses are initiated through interactions between antigen presenting cells (APCs) and T cells. The type and strength of signals delivered through the T cell receptor (TCR) may modulate how the cells respond. The TCR-MHC (T cell receptor-major histocompatibility complex molecules) complex dictates the specificity, whereas co-stimulatory signals induced by interaction of various accessory cell surface molecules strengthen and optimize T cell responses. Multiple immune regulatory mechanisms brought about by co-inhibitory molecules expressed on T cells play a key role in orchestrating successful and non-damaging immunity. These co-inhibitory molecules are also referred to as initiators of immune check-points or co-inhibitory pathways. Knowledge of co-inhibitory pathways associated with activated T lymphocytes has allowed a better understanding of (a) the inflammatory and anti-inflammatory processes associated with infectious diseases and autoimmune diseases, and (b) mechanisms by which tumors evade immune attack. Many of these regulatory pathways are non-redundant and function in a highly concerted manner. Targeting them has provided effective approaches in treating cancer and autoimmune diseases. For this reason, it is valuable to identify any co-inhibitory molecules that affect these pathways. MUC1 mucin (CD227) has long been known to be expressed by epithelial cells and overexpressed by a multitude of adenocarcinomas. As long ago as 1998 we made a surprising discovery that MUC1 is also expressed by activated human T cells and we provided the first evidence of the role of MUC1 as a novel T cell regulator. Subsequent studies from different laboratories, as well as ours, supported an immuno-regulatory role of MUC1 in infections, inflammation, and autoimmunity that corroborated our original findings establishing MUC1 as a novel T cell regulatory molecule. In this article, we will discuss the experimental evidence supporting MUC1 as a putative regulatory molecule or a "checkpoint molecule" of T cells with implications as a novel biomarker and therapeutic target in chronic diseases such as autoimmunity, inflammation and cancer, and possibly infections.

Future Path Toward TB Vaccine Development: Boosting BCG or Re-educating by a New Subunit Vaccine.

Tuberculosis (TB), an infectious disease caused by Mycobacterium tuberculosis (Mtb), kills 5,000 people per day globally. Rapid development and spread of various multi drug-resistant strains of Mtb emphasize that an effective vaccine is still the most cost-effectives and efficient way of controlling and eradicating TB. Bacillus Calmette-Guerin (BCG), the only licensed TB vaccine, still remains the most widely administered human vaccine, but is inefficient in protecting from pulmonary TB in adults. The protective immunity afforded by BCG is thought to wane with time and considered to last only through adolescent years. Heterologous boosting of BCG-primed immune responses using a subunit vaccine represents a promising vaccination approach to promote strong cellular responses against Mtb. In our earlier studies, we discovered lipopeptides of ESAT-6 antigen with strong potential as a subunit vaccine candidate. Here, we have investigated that potential as a booster to BCG vaccine in both a pre-exposure preventive vaccine and a post-exposure therapeutic vaccine setting. Surprisingly, our results demonstrated that boosting BCG with subunit vaccine shortly before Mtb challenge did not improve the BCG-primed immunity, whereas the subunit vaccine boost after Mtb challenge markedly improved the quantity and quality of effector T cell responses and significantly reduced Mtb load in lungs, liver and spleen in mice. These studies suggest that ESAT-6 lipopeptide-based subunit vaccine was ineffective in overcoming the apparent immunomodulation induced by BCG vaccine in Mtb uninfected mice, but upon infection, the subunit vaccine is effective in re-educating the protective immunity against Mtb infection. These important results have significant implications in the design and investigation of effective vaccine strategies and immunotherapeutic approaches for individuals who have been pre-immunized with BCG vaccine but still get infected with Mtb.

New Players in Immunity to Tuberculosis: The Host Microbiome, Lung Epithelium, and Innate Immune Cells.

Tuberculosis (TB) is a highly contagious infection and devastating chronic disease, causing 10.4 million new infections and 1.8 million deaths every year globally. Efforts to control and eradicate TB are hampered by the rapid emergence of drug resistance and limited efficacy of the only available vaccine, BCG. Immunological events in the airways and lungs are of major importance in determining whether exposure to Mycobacterium tuberculosis (Mtb) results in successful infection or protective immunity. Several studies have demonstrated that the host microbiota is in constant contact with the immune system, and thus continually directs the nature of immune responses occurring during new infections. However, little is known about its role in the eventual outcome of the mycobacterial infection. In this review, we highlight the changes in microbial composition in the respiratory tract and gut that have been linked to the alteration of immune responses, and to the risk, prevention, and treatment of TB. In addition, we summarize our current understanding of alveolar epithelial cells and the innate immune system, and their interaction with Mtb during early infection. Extensive studies are warranted to fully understand the all-inclusive role of the lung microbiota, its interaction with epithelium and innate immune responses and resulting adaptive immune responses, and in the pathogenesis and/or protection from Mtb infection. Novel interventions aimed at influencing the microbiota, the alveolar immune system and innate immunity will shape future strategies of prevention and treatment for TB.

Incidence and Predictors of Readmissions in Acute Pancreatitis: A Nationwide Analysis.

OBJECTIVES: Acute pancreatitis (AP) is a common cause for hospitalization, and readmission is common, with variable associated risk factors for readmission. Here, we assessed the incidence and risk factors for readmission in AP in a large national database. METHODS: We analyzed data from the National Readmission Database during the year 2013. Index admissions with a primary discharge diagnosis of AP using the International Classification of Diseases, Ninth Revision, Clinical Modification were identified from January to November to identify 30-day readmission rates. Demographic, hospital, and clinical diagnoses were included in multivariate regression analysis to identify readmission risk factors. RESULTS: We identified 243,816 index AP discharges with 39,623 (16.2%) readmitted within 30 days. The most common reason for readmission was recurrent AP (41.5%). Increased odds of all-cause readmission were associated with younger age, nonhome discharge, increasing Charlson Comorbidity Index, and increased length of stay. Cholecystectomy during index admission was associated with reduced all-cause and recurrent AP readmissions (odds ratios of 0.5, and 0.35, respectively). CONCLUSIONS: Readmission for AP is common, most often due to recurrent AP. Multiple factors, including cholecystectomy, during index admission, are associated with significantly reduced odds of all-cause and recurrent AP readmissions.

Unsolved Puzzles Surrounding HCV Immunity: Heterologous Immunity Adds Another Dimension.

Chronic infection with hepatitis C virus (HCV) afflicts 3% of the world's population and can lead to serious and late-stage liver diseases. Developing a vaccine for HCV is challenging because the correlates of protection are uncertain and traditional vaccine approaches do not work. Studies of natural immunity to HCV in humans have resulted in many enigmas. Human beings are not immunologically naïve because they are continually exposed to various environmental microbes and antigens, creating large populations of memory T cells. Heterologous immunity occurs when this pool of memory T cells cross-react against a new pathogen in an individual. Such heterologous immunity could influence the outcome when an individual is infected by a pathogen. We have recently made an unexpected finding that adenoviruses, a common environmental pathogen and an experimental vaccine vector, can induce robust cross-reactive immune responses against multiple antigens of HCV. Our unique finding of previously uncharacterized heterologous immunity against HCV opens new avenues to understand HCV pathogenesis and develop effective vaccines.