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.

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.

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.

Coronary Artery Disease in Patients With Disorders of Bilirubin Excretion.

We aimed to determine the predictors of coronary artery disease (CAD) in patients with abnormal bilirubin excretion, that is, Gilbert syndrome, Crigler-Najjar syndrome, Dubin-Johnson syndrome, and Rotor syndrome. We analyzed data from the Healthcare Cost and Utilization Project (HCUP) of the Agency for Healthcare Research and Quality, Rockville, MD for the period 2009 to 2010. All patients ≥18 years of age with a primary diagnosis of "disorders of bilirubin excretion" [International Classification of Diseases, Ninth Edition, Clinical Modification (ICD-9CM) code 277.4] were included in the study. Primary outcome was to determine predictors of CAD in adult patients diagnosed with abnormal bilirubin excretion. We identified a total of 12,423 adult patients with bilirubin excretion disorder hospitalized during 2009-2010 (0.03% of all inpatient admissions). CAD was seen in 18% of patients, with a higher prevalence in men (21% in men vs. 13% in women, P < 0.0001). In multivariate logistic regression adjusted for demographic and traditional risk factors, hypertension [odds ratio (OR): 1.74; 95% confidence interval (CI), 1.33-2.27, P < 0.001], hyperlipidemia (OR: 2.49; 95% CI, 1.95-3.18, P < 0.001), diabetes (OR: 1.46; 95% CI, 1.12-1.91, P = 0.01), and age (OR: 1.05; 95% CI, 1.04-1.06, P < 0.001) were found to be independent predictors of CAD in adult patients with abnormal bilirubin excretion. Female sex (OR: 0.49; 95% CI, 0.36-0.65, P < 0.001) demonstrated an inverse association in predicting CAD. There was increased prevalence of CAD in our patient population with increased prevalence of cardiovascular risk factors. Age, diabetes mellitus, hypertension, and hyperlipidemia were found to be independent predictors of CAD.

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.

Constipation and Outcomes of Cecostomy.

Constipation, defined as delay or difficulty in defecation, present for 2 or more weeks, is a common problem encountered by both primary and specialty medical providers. There are no randomized controlled trials on the use of antegrade enemas in the pediatric population. Most published papers are based on the experience at a particular center. The aim of this article is to describe the pathophysiology of constipation, review the contribution of colonic manometry to the diagnosis of constipation, summarize the advancements in the management of constipation through the use of antegrade enemas, and study the outcomes of cecostomy at different centers. This study is a comprehensive literature review generated by computerized search of literature, supplemented by review of monographs and textbooks in pathology, gastroenterology, and surgery. Literature search was performed using the publications from 1997 to 2012. The search included publications of all types presenting or reviewing data on cecostomy. The antegrade continence enema is a therapeutic option for defecation disorders when maximal conventional therapy is not successful. Symptoms of defecation disorders in children with different underlying etiologies improve significantly after a cecostomy is created. In addition, there is a benefit on the patients' physical activity, healthcare utilization, and general well-being. Based on the review of published literature it seems that antegrade enemas are a successful therapeutic option in children with severe constipation and/or fecal incontinence. With the advent of cecostomy buttons, patient compliance and the overall cosmetic appearance have improved.

The management of eosinophilic gastroenteritis.

Eosinophilic gastroenteritis (EG) is a rare disorder characterized by eosinophilic infiltration of the gastrointestinal tract. No medication at present is approved by the Food and drug administration of United States for the treatment of EG. The rarity of the disease limits our experience with the different management options. It also limits the ability to conduct randomized controlled trials that could clearly delineate the efficacy of new therapeutic agents. This review assesses the various management options that have been tried on patients with EG.

Autoimmune Hepatitis in Association With Sofosbuvir.

Sofosbuvir in combination with ribavirin was approved by the Food and Drug Administration as a treatment option for hepatitis C (HepC) in 2013. We describe a case of autoimmune hepatitis triggered in a patient on therapy with sofosbuvir and ribavirin. A 65-year-old woman with a medical history of diabetes mellitus, hypertension, and HepC (genotype 2) underwent pretreatment liver biopsy in May 2012, which demonstrated mild chronic active hepatitis with focal piece-meal necrosis and mild stage 1 periportal fibrosis with no increased iron deposition. No features of autoimmune hepatitis were seen on biopsy. The patient was administered 400 milligrams (mg) sofosbuvir and weight-based 1000 mg ribavirin for a planned duration of 12 weeks. Liver function tests (LFTs) initially improved on therapy; however, 3 weeks after the treatment initiation, the patient started complaining of weakness and fatigue. Repeat tests revealed elevated LFTs. Autoimmune titers were positive for antinuclear antibody, anti-smooth muscle antibody with elevated immunoglobulin (IgG), and serum gamma globulin levels. Repeat liver biopsy in June 2014 showed markedly distorted architecture secondary to formation of nodules completely enclosed by fibrous septa and areas of confluent necrosis with mild to moderate chronic inflammation consisting mainly of lymphocytes and plasma cells along with moderate to severe interface hepatitis. Ballooning degeneration of hepatocytes, with rosette formation possibly associated with regenerative activity was seen, consistent with superimposed autoimmune hepatitis. Based on laboratory and biopsy findings, diagnosis of drug-induced autoimmune hepatitis was made, and the treatment for HepC with sofosbuvir and ribavirin was discontinued. The patient was subsequently administered prednisolone with improvement in LFTs. We describe a patient with autoimmune hepatitis after initiation of sofosbuvir and ribavirin. To our knowledge, this complication has never been reported before in association with sofosbuvir. The most frequent adverse events noticed with this combination regimen have been headache, anemia, fatigue, and nausea.

Diagnosis and management of dementia in primary care: exploratory study.

OBJECTIVE: To assess the current identification and management of patients with dementia in a primary care setting; to determine the accuracy of identification of dementia by primary care physicians; to examine reasons (triggers) for referral of patients with suspected dementia to the geriatric assessment team (GAT) from the primary care setting; and to compare indices of identification and management of dementia between the GAT and primary care network (PCN) physicians and between the GAT and community care (CC). DESIGN: Retrospective chart review and comparisons, based on quality indicators of dementia care as specified in the Third Canadian Consensus Conference on the Diagnosis and Treatment of Dementia, were conducted from matching charts obtained from 3 groups of health care providers. SETTING: Semirural region in the province of Alberta involving a PCN, CC, and a GAT. PARTICIPANTS: One hundred patients who had been assessed by the GAT randomly selected from among those diagnosed with dementia or mild cognitive impairment by the GAT. MAIN OUTCOME MEASURES: Diagnosis of dementia and indications of high-quality dementia care listed in PCN, CC, and GAT charts. RESULTS: Only 59% of the patients diagnosed with dementia by the GAT had a documented diagnosis of dementia in their PCN charts. None of the 12 patients diagnosed with mild cognitive impairment by the GAT had been diagnosed by the PCN. Memory decline was the most common reason for referral to the GAT. There were statistically significant differences between the PCN and the GAT on all quality indicators of dementia, with underuse of diagnostic and functional assessment tools and lack of attention to wandering, driving, medicolegal, and caregiver issues, and underuse of community supports in the PCN. There was higher congruence between CC and the GAT on assessment and care indices. CONCLUSION: Dementia care remains a challenge in primary care. Within our primary care setting, there are opportunities for synergistic collaboration among the health care professionals from the PCN, CC, and the GAT. Currently they exist as individual entities in the system. An integrated model of care is required in order to build capacity to meet the needs of an aging population.

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.

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.

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.

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.

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.

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.