Natural Pigments-Based Two-Component White Light Emitting Systems.

In this paper, a new class of two component white light emitting systems viz, JaB (java plum + beetroot) {I}, and CaB (carrot + beetroot) {II} were developed through resonance energy transfer (RET) phenomenon by using a fruit (java plum) and two vegetable (carrot and beetroot) extracts. In these white light emitting systems, java plum and carrot are the donors while beetroot is the acceptor. The primary fluorescent pigments present in the natural extracts (i.e., anthocyanin in java plum, ß-carotene in carrot, and betanin in beetroot) were responsible for the white light emission. The CIE (Commission Internationale d'Eclairage) coordinates for I and II were {0.32, 0.34} and {0.33, 0.33}, respectively, in solution phase. Interestingly, the white light emission (WLE) was also achieved in agar-agar gel medium. In gel medium, the CIE values were {0.31, 0.34} and {0.33, 0.32} for I and II, respectively. The donor-acceptor distance (r) for I and II were found to be 0.5 and 0.4 nm, respectively. Furthermore, the rate of energy transfer was also quantified with the values of 2.78 × 109 s-1 for JaB (I) and 1.02 × 108 s-1 for CaB (II) systems. The mechanistic investigation of the two white light systems was further supported by DFT studies.

CYP450 Genetic Polymorphisms: Generalized Tonic-Clonic Seizure after Intentional Fluoxetine and Melatonin Overdose.

Cytochrome P450 polymorphisms have gathered much attention regarding personalized psychopharmacological care. It is well documented that these drug metabolizing enzymes lead to interpatient variability in pharmacokinetic profiles. It appears that less functional genotype may increase of risk of higher side-effect burden. Here we highlight the importance of genetic polymorphisms to potentially predict a toxicity related phenotype after an intentional overdose. Genotyping may have a role in predicting serious side effects to help clinicians educate patients and their families, and implement more intensive monitoring and institute prophylactic treatment as needed.

Attention-Deficit Hyperactivity Disorder Status Moderates Polysubstance Use Among Substance Using Populations: A Cross-Sectional Analysis.

INTRODUCTION: Attention-deficit hyperactivity disorder (ADHD) increases the risk for comorbid psychiatric and substance use disorders, which may increase the risk of adverse patient outcomes. This study examined the prevalence of ADHD in residential addiction treatment as well as the prevalence of mono-substance use, comorbid substance use, and polysubstance use disorders (PUD) as a function of ADHD status. METHODS: All participants were adults (18 years and older) admitted to a residential substance use disorder treatment center in Sioux Falls, SD. Participants were administered a Wender Utah ADHD rating scale to assess ADHD status using a cutoff score of 46. The participants were administered ADHD questionnaires developed to assess ADHD history, family history, and academic performance. RESULTS: Students showed a 17% increase in confidence in discussing substance use with patients and a 47% increase in confidence in applying MI techniques after the instructional session. At CC, 54.5% of patients reported substance use and 16.7% of those patients responded that they would consider quitting in the next month after the student interview. In the post-clinic survey, students rated an average of 4.21 out of 5 on comfort level in discussing excessive substance use. CONCLUSION: ADHD and substance use disorder have notable comorbidity. This study demonstrates a high prevalence of ADHD in populations with substance use disorder. The presence of ADHD may be a risk factor for PUD. Effective screening and treatment of ADHD may alleviate substance use burden among users.

Metabolic stress induces GD2+ cancer stem cell-like phenotype in triple-negative breast cancer.

BACKGROUND: Metabolic stress resulting from nutrient deficiency is one of the hallmarks of a growing tumour. Here, we tested the hypothesis that metabolic stress induces breast cancer stem-like cell (BCSC) phenotype in triple-negative breast cancer (TNBC). METHODS: Flow cytometry for GD2 expression, mass spectrometry and Ingenuity Pathway Analysis for metabolomics, bioinformatics, in vitro tumorigenesis and in vivo models were used. RESULTS: Serum/glucose deprivation not only increased stress markers but also enhanced GD2+ BCSC phenotype and function in TNBC cells. Global metabolomics profiling identified upregulation of glutathione biosynthesis in GD2high cells, suggesting a role of glutamine in the BCSC phenotype. Cueing from the upregulation of the glutamine transporters in primary breast tumours, inhibition of glutamine uptake using small-molecule inhibitor V9302 reduced GD2+ cells by 70-80% and BCSC characteristics in TNBC cells. Mechanistic studies revealed inhibition of the mTOR pathway and induction of ferroptosis by V9302 in TNBC cells. Finally, inhibition of glutamine uptake significantly reduced in vivo tumour growth in a TNBC patient-derived xenograft model using NSG (non-obese diabetic/severe combined immunodeficiency with a complete null allele of the IL-2 receptor common gamma chain) mice. CONCLUSION: Here, we show metabolic stress results in GD2+ BCSC phenotype in TNBC and glutamine contributes to GD2+ phenotype, and targeting the glutamine transporters could complement conventional chemotherapy in TNBC.

Mechanistic investigation of formation of highly-dispersed silver nanoparticles using sea buckthorn extract.

Nowadays, the greener pathways for the synthesis of nanostructures are being explored. The extracts of different parts of plantsvizleaves, stems, and roots have been investigated. However, these extracts have been prepared by simply boiling or microwaving, or sonicating the parts of plants with water. Therefore, to have deeper insight and to investigate the full potential of plant extracts, serial extraction of leaves of sea buckthorn (Hippophae rhamnoides L.) which is a medicinally important plant was attempted using the soxhlet apparatus. The as-obtained polyphenolic-rich extract was employed for the preparation of silver nanoparticles (Ag-NPs). Under optimized reaction conditionsviz60 °C temperature and 500µl of extract solution (5 mg ml-1) highly disperse spherical nanoparticles of the average size of 15.8 ± 4.8 nm were obtained. Further, the optical band gap of Ag-NPs prepared using optimized reaction conditions was found to be 2.6 eV using the Tauc equation. Additionally, to understand the reduction by the extract, kinetic studies were also carried out which suggest the predominant occurrence of pseudo-first-order reaction. Furthermore, the mechanism of formation of Ag-NPs using major components of extractvizgallic acid and catechin which were identified by HPLC were also investigated using DFT. The mechanistic investigation was performed for both the keto-enol and radical-mediated preparation of Ag-NPs. Such theoretical investigations will help in the efficient designing of greener and novel routes for the synthesis of Ag-NPs. Additionally, the prepared silver was also employed for the colorimetric detection of H2O2.

Empirically Validated Screening Tools for Adolescent Substance Use Disorders.

Substance use is a major cause of morbidity and mortality in the U.S., and data from treatment centers shows that 75 percent of patients initiated their use prior to the age of 17 years. Substance use in the adolescent years affects brain development and leads to poor physical and psychiatric health, decreased academic performance, and forensic outcomes. Screening at both primary care and specialty visits allows for early intervention and treatment. This article reviews the available screening tools for substance use disorders in children and adolescents for use in a variety of clinical settings.

Uncovering an Uncommon Diagnosis: Relapsing Adolescent Catatonia.

Catatonia in the pediatric population is a historically overlooked syndrome. Accurate recognition is complicated by a broad differential diagnosis and co-morbid substance use, particularly in adolescent patients. Prompt treatment is vital to avoid life-threatening complications such as malignant catatonia. This article summarizes a case of relapsing adolescent catatonia and discusses the pathway of diagnosis and treatment.

Biglycan: an emerging small leucine-rich proteoglycan (SLRP) marker and its clinicopathological significance.

Extracellular matrix (ECM) plays an important role in the structural organization of tissue and delivery of external cues to the cell. Biglycan, a class I small leucine-rich proteoglycans (SLRP), is a key component of the ECM that participates in scaffolding the collagen fibrils and mediates cell signaling. Dysregulation of biglycan expression can result in wide range of clinical conditions such as metabolic disorder, inflammatory disorder, musculoskeletal defects and malignancies. In this review, we aim to update our current understanding regarding the link between altered expression of biglycan and different clinicopathological states. Biglycan interacts with toll like receptors (TLR)-2 and TLR-4 on the immune cells which initiates inflammation and aggravates inflammatory disorders. ECM unbound soluble biglycan acts as a DAMP (danger associated molecular pattern) resulting in sterile inflammation. Dysregulation of biglycan expression is also observed in inflammatory metabolic conditions such as atherosclerosis and obesity. In cancer, high-biglycan expression facilitates tumor growth, invasion and metastasis which is associated with poor clinical outcome. As a pivotal structural component of the ECM, biglycan strengthens the musculoskeletal system and its absence is associated with musculoskeletal defects. Thus, SLRP biglycan is a potential marker which is significantly altered in different clinicopathological states.

Adolescent Vaping and COVID-19: When an Epidemic Meets a Pandemic.

National epidemiological studies indicate that vaping or e-cigarette use has increased in alarming proportions among American adolescents. In vaping, a battery-powered device heats up a liquid into an aerosol which is inhaled by the user. The aerosol, commonly referred to as vapor, usually contains nicotine, flavoring, marijuana along with other chemicals and substances. This article highlights serious yet avoidable health risks from vaping amidst the coronavirus disease 2019 (COVID-19) pandemic. Vaping may mediate transmission, infections, disease progression and risk of succumbing to COVID-19. An overview of possible solutions and resources for South Dakota physicians is also discussed.

Long-acting Methylphenidate Induced Transient Orofacial Dyskinesia and Upper Extremity Choreoathetosis: A Case Report.

Attention-deficit/hyperactivity disorder (ADHD) is a commonly encountered diagnosis in the child and adolescent populations, and stimulant medications are often prescribed for their treatment. There are numerous available options in this category, including immediate and extended release formulations. There have been many case reports in the literature involving purposeful overdose on immediate release stimulants, but a relative paucity involving extended release forms. Additionally, they often involve Caucasian and Asian populations. We treated a Native American adolescent who took an overdose of extended-release methylphenidate with the intention of suicide. He developed transient orofacial dyskinesia and upper extremity choreoathetosis as a result which did not abate during his time in the emergency department. Once transferred to our care, he was given a one-time benzodiazepine dose with some benefit. This case report describes objective sequelae of a long-acting methylphenidate overdose as well as treatment for the benefit of treating clinicians with similar patient populations and situations.

Seroconversion among COVID-19 patients admitted in a dedicated COVID hospital: A longitudinal prospective study of 1000 patients.

BACKGROUND: The immune response after SARS-CoV-2 is complex and may be affected by severity of the disease, race, etc. The present study was conducted to assess the serial antibody response among the COVID-19 patients admitted in the hospital. METHODS: The study was conducted between July and October 2020 in a dedicated COVID-19 hospital. All consented patients underwent serial testing of antibodies using a rapid chromatographic immunoassay-based qualitative IgG/IgM kit every third day until their discharge or death. The data about age, sex, severity of disease, length of stay, onset of symptoms, date of molecular testing were also collected. Appropriate statistical tests were used. RESULTS: The mean age of 1000 COVID-19 patients was 47.5 ± 17.9 years. Out of the total, 687 (68.7%) were males. With respect to severity, 682 (68.2%) were asymptomatic/mild, 200 (20%) were moderate and 118 (11.8%) were severe cases. The seroconversion percentage increased from 12.8% to 97.9% and 16.3% to 80.9% for IgG and IgM respectively in 21 days. The median time for seroconversion was 10 days (IQR:6-12 days) for IgG and eight days (IQR: 6-11 days) for IgM. At the time of discharge (median nine days), detectable IgG and IgM antibodies were present in 502 (52.46%) and 414 (43.26%) participants respectively. Seroconversion was associated with days after the symptoms, increasing severity of the disease and the presence of co-morbidity. CONCLUSION: Seroconversion increased during the period of observation. The severe/moderate cases of COVID-19 tend to have an early seroconversion as compared to the asymptomatic/mild cases. Only half of the patients were seroconverted at discharge.

RASSF1A-Hippo pathway link in patients with urothelial carcinoma of bladder: plausible therapeutic target.

RASSF1A is a tumor suppressor gene, and its hypermethylation has been observed in cancers. RASSF1A acts as an upstream regulator of Hippo pathway and modulates its function. The aim of this study was to analyze expression of RASSF1A, Hippo pathway molecules (YAP, MST) and downstream targets (CTGF, Cyr61 and AREG) in bladder cancer patients. Later, the link between RASSF1A and Hippo pathway and a potential therapeutic scope of this link in UBC were also studied. MSPCR was performed to study methylation of RASSF1A promoter. Expression of molecules was studied using qPCR, Western blot and IHC. The link between RASSF1A and Hippo pathway was studied using Spearman's correlation in patients and validated by overexpressing RASSF1A in HT1376 cells and its effect on Hippo pathway was observed using qPCR and Western blot. Further therapeutic potential of this link was studied using MTT and PI assays. The expression of RASSF1A was lower, whereas the expression of YAP, CTGF and CYR61 was higher. The expression of RASSF1A protein gradually decreased, while the expression of YAP, CTGF and CYR61 increased with severity of disease. Based on Spearman's correlation, RASSF1A showed a negative correlation with YAP, CTGF and CYR61. YAP showed a positive correlation with CTGF and CYR61. To validate this link, RASSF1A was overexpressed in HT1376 cells. Overexpressed RASSF1A activated Hippo pathway, followed by a decrease in CTGF and CYR61 at mRNA, and enhanced cytotoxicity to chemotherapeutic drugs. This study finds a previously unrecognized role of RASSF1A in the regulation of CTGF and CYR61 through mediation of Hippo pathway in UBC and supports the significance of this link as a potential therapeutic target for UBC.

Distant supervision for medical concept normalization.

We consider the task of Medical Concept Normalization (MCN) which aims to map informal medical phrases such as "loosing weight" to formal medical concepts, such as "Weight loss". Deep learning models have shown high performance across various MCN datasets containing small number of target concepts along with adequate number of training examples per concept. However, scaling these models to millions of medical concepts entails the creation of much larger datasets which is cost and effort intensive. Recent works have shown that training MCN models using automatically labeled examples extracted from medical knowledge bases partially alleviates this problem. We extend this idea by computationally creating a distant dataset from patient discussion forums. We extract informal medical phrases and medical concepts from these forums using a synthetically trained classifier and an off-the-shelf medical entity linker respectively. We use pretrained sentence encoding models to find the k-nearest phrases corresponding to each medical concept. These mappings are used in combination with the examples obtained from medical knowledge bases to train an MCN model. Our approach outperforms the previous state-of-the-art by 15.9% and 17.1% classification accuracy across two datasets while avoiding manual labeling.

Humanizing an Invisible Population in India: Voices from Bisexual Men Concerning Identity, Life Experiences, and Sexual Health.

Research examining the sexual identities, behaviors, and experiences of bisexual men outside of Western contexts (including in India) is limited. Individuals who self-identify as bisexual due to their orientation toward partners of more than one gender face distinct psychosocial challenges relative to exclusively heterosexual, gay/lesbian, or other individuals. We conducted four focus group discussions (n = 22) and in-depth interviews (n = 50) with self-identified bisexual men (age 18 years and older) who were recruited from the metropolitan area of Mumbai, India, between June and August 2013. We triangulated and analyzed focus group and interview data using standard qualitative research techniques. Findings from our study suggest that multiple factors influence the sexual experiences of self-identified bisexual men in Mumbai, including contexts of sexual interactions, sexual positioning, and the gender of sexual partners. Participants described cultural meaning systems and psychosocial dynamics that regulate bisexual identity development, disclosure, and sexual decision making with male, female, and other partners. Secrecy, discretion, and sexual pleasure also influenced sexual behaviors and relationships. Although Western sexual identity categories are not necessarily equivalent in the Indian context, it is interesting and important to note that a number of individuals in India continue to use the identity label of "bisexual." Before developing interventions to meet unique sexual health needs of bisexual men, it is crucial to understand how these men perceive themselves, reconcile the ordinary aspects of their lives with their sexuality, and structure their relationships with partners.

T helper type 1 polarizing γδ T cells and Scavenger receptors contribute to the pathogenesis of Pemphigus vulgaris.

γδ T cells and Scavenger receptors are key parts of the innate immune machinery, playing significant roles in regulating immune homeostasis at the epithelial surface. The roles of these immune components are not yet characterized for the autoimmune skin disorder Pemphigus vulgaris (PV). Phenotyping and frequency of γδ T cells estimated by flow cytometry have shown increased frequency of γδ T cells (6·7% versus 4·4%) producing interferon- γ (IFN-γ; 35·2% versus 26·68%) in the circulation of patients compared with controls. Dual cytokine-secreting (IFN-γ and interleukin-4) γδ T cells indicate the plasticity of these cells. The γδ T cells of patients with PV have shown higher cytotoxic potential and the higher frequency of γδ T cells producing IFN-γ shows T helper type 1 polarization. The increased expression of Scavenger receptors expression (CD36 and CD163) could be contributing to the elevated inflammatory environment and immune imbalance in this disease. Targeting the inflammatory γδ T cells and Scavenger receptors may pave the way for novel therapeutics.

Decitabine augments cytotoxicity of cisplatin and doxorubicin to bladder cancer cells by activating hippo pathway through RASSF1A.

Genetic abnormalities and epigenetic alterations both play vital role in initiation as well as progression of cancer. Whereas genetic mutations cannot be reversed, epigenetic alterations such as DNA methylation can be reversed by the application of DNA methyltransferase inhibitor decitabine. Epigenetic silencing of RASSF1A and involvement of hippo pathway both have been shown to involve in chemo-resistance. Purpose of this study was to observe the effect of combination treatment of decitabine with cisplatin or doxorubicin on bladder cancer cells involving hippo pathway through RASSF1A. Bladder cancer cells (HT1376 & T24) were treated with decitabine and its effect on RASSF1A expression, hippo pathway molecules (MST & YAP), and its downstream targets (CTGF, CYR61 & CTGF) was observed. Effect of decitabine pretreatment on sensitivity of bladder cancer cells towards chemotherapeutic drugs was also studied. Decitabine treatment leads to restoration of RASSF1A, activation of hippo pathway followed by decreased expression of its oncogenic downstream targets (CTGF & CYR61). Further pretreatment of decitabine enhanced cytotoxicity of cisplatin and doxorubicin to bladder cancer cells.

Hydroxyethyl starch and kidney function: A retrospective study in patients undergoing therapeutic plasma exchange.

PURPOSE: Hydroxyethyl starch (HES) and albumin are used as replacement fluids during therapeutic plasma exchange (TPE). HES solutions are no longer recommended in critically ill patients due to its effect on kidneys and coagulation. In this retrospective study, we tried to look at the association between cumulative HES administration and kidney function in patients undergoing TPE. METHODS: Transfusion medicine department register was scrutinized to identify adult patients who had completed at least 5 cycles of TPE during the period June 2014-May 2015. Patient demographics, indication for TPE, amount of plasma removed, amount of colloid administered, adverse events and vascular access details were collected. Electronic hospital database was scrutinized to retrieve lab parameters, including blood urea and serum creatinine (before and after 5 cycles of TPE) and platelet count. Baseline renal parameters were compared with post TPE values using Wilcoxon signed rank test. A p value <0.05 was kept as significant. RESULTS: Of the 593 patients who received TPE during the study period, 104 patients fulfilled the inclusion criteria. Forty-five patients out of 104 received TPE in the intensive care unit. All patients received 2500 ml of HES during the study period. Blood urea and serum creatinine values, when compared to baseline, significantly decreased after 5 cycles of TPE (p = 0.004, p = 0.001, respectively). CONCLUSION: Blood urea and serum creatinine, used as markers of renal function, improved in patients requiring multiple doses of HES solutions during TPE. Further studies using novel renal biomarkers are required to examine whether HES induces any structural damage to kidneys.

A randomized clinical efficacy trial of a psychosocial intervention to strengthen self-acceptance and reduce HIV risk for MSM in India: study protocol.

BACKGROUND: Men who have sex with men (MSM) in India are a key group at risk for HIV acquisition and transmission. They are also an extremely marginalized and stigmatized population, facing immense psychosocial stressors including, but not limited to, stigma, homophobia, discrimination, criminalization, low self-esteem, low self-acceptance, distress, and, as a result, high rates of mental health problems. Although these multi-level psychosocial problems may put MSM at high risk for HIV acquisition and transmission, currently HIV prevention interventions in India do not address them. This paper describes the design of a psychosocial intervention to reduce HIV risk for MSM in India. METHODS: Funded by the National Institute of Mental Health, this study is a two-arm randomized clinical efficacy trial of a self-acceptance based psychosocial HIV prevention intervention, informed by the minority stress model and syndemic theory, that was developed with extensive community-based formative work and input from the Indian MSM community and key informants who are knowledgeable about the experiences faced by MSM in India. Participants are MSM in Chennai and Mumbai who endorsed recent sexual behaviors placing them at high risk for HIV/sexually transmitted infection (STI) acquisition and transmission. Enrolled participants are equally randomized to either 1) the experimental condition, which consists of four group and six individual counseling sessions and includes standard of care HIV/STI testing and counseling, or 2) the standard of care condition, which includes HIV/STI testing and counseling alone. The primary outcomes are changes in the frequency of condomless anal sex acts and STI incidence (syphilis seropositivity and urethral, rectal, and pharyngeal gonorrhea and chlamydia infection. Major study assessment visits occur at baseline, 4-, 8-, and 12-months. DISCUSSION: HIV prevention interventions that address the psychosocial stressors faced by MSM in India are needed; this study will examine the efficacy of such an intervention. If the intervention is successful, it may be able to reduce the national HIV/AIDS burden in India while empowering a marginalized and highly stigmatized group. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02556294 , registered 22 September 2015.

Social support relationships for sexual minority women in Mumbai, India: a photo elicitation interview study.

Little research exists on women who do not identify as heterosexual in India. Social support for sexual minority women may protect against the effects of discrimination. An examination of significant social relationships may point to both strengths and weaknesses in this support. We aimed to understand relationship prioritisation and communication patterns associated with the social support of sexual minority women in Mumbai. In partnership with the Humsafar Trust, India's oldest and largest sexual and gender minority-advocacy organisation, we conducted photo-elicitation interviews with 18 sexual minority women, using participants' photographs to prompt dialogue about their social support. Intimate partners were a source of dependable support and many of those without relationships were seeking them. Participants' extended networks included friends and family as well as less formal relationships of social support. Participants mediated their communication with particular social network members, which involved filtering information sexual identity, romantic interests, and personal aspirations, among others. The diverse relationships that sexual minority women have in their social support networks may be used to guide programmes to improve health outcomes.

Altered expression of small leucine-rich proteoglycans (Decorin, Biglycan and Lumican): Plausible diagnostic marker in urothelial carcinoma of bladder.

Small leucine-rich proteoglycans are components of extracellular matrix that regulates neoplastic transformation. Among small leucine rich proteoglycans, Decorin, Biglycan and Lumican are most commonly implicated markers, and their expression is well studied in various malignancies. In this novel study, we have collectively evaluated expression of these three molecules in urothelial carcinoma of bladder. Thirty patients of confirmed untreated bladder cancer, 30 healthy controls for blood and 30 controls for adjacent non-tumour tissue were enrolled. Blood was collected from all subjects and tumour/adjacent normal tissue was obtained from the patients. Circulatory levels were estimated by enzyme-linked immunosorbent assay, relative messenger RNA expression by quantitative polymerase chain reaction and protein expression by immunohistochemistry and western-blotting. Circulatory levels of Biglycan (p = 0.0038) and Lumican (p < 0.0001) were significantly elevated, and that of Decorin (p < 0.0001) was significantly reduced in patients as compared with controls. Protein expression by immunohistochemistry and western-blotting showed elevated expression of Lumican and Biglycan and lower expression of Decorin in urothelial carcinoma of bladder. Quantitative polymerase chain reaction for messenger RNA expression from tissue specimens revealed significantly higher expression of Biglycan (p = 0.0008) and Lumican (p = 0.01) and lower expression of Decorin (p < 0.0001) in urothelial carcinoma of bladder. Out of all molecules receiver operating characteristic curve showed that the 0.207 ng/ml cut-off of serum Lumican provided optimum sensitivity (90.0%) and specificity (90.0%). Significant alteration of matrix small leucine-rich proteoglycans in urothelial carcinoma of bladder was observed. Higher expression of Lumican in Bladder cancer patients with the cut-off value of highest optimum sensitivity and specificity shows its importance as a potential non-invasive marker for early detection of UBC following further validation in large patient cohort.