Pain/Stress, Mitochondrial Dysfunction and Neurodevelopment in Preterm Infants.

Introduction Preterm infants experience tremendous early life pain/stress during their neonatal intensive care unit (NICU) hospitalization, which impacts their neurodevelopmental outcomes. Mitochondrial function/dysfunction may interface between perinatal stress events and neurodevelopment. Nevertheless, the specific proteins or pathways linking mitochondrial functions to pain-induced neurodevelopmental outcomes in infants are remain unidentified. Our study aims to investigate the associations among pain/stress, proteins associated with mitochondrial function/dysfunction, and neurobehavioral responses in preterm infants. Methods We conducted a prospective cohort study, enrolling 33 preterm infants between September 2017 and July 2022 at two affiliated NICUs located in Hartford and Farmington, CT. NICU Network Neurobehavioral Scale (NNNS) datasets were evaluated to explore potential association with neurobehavioral outcomes. The daily pain/stress experienced by infant's during their NICU stay was documented. At 36-38 weeks post-menstrual age (PMA), neurobehavioral outcomes were evaluated using the NNNS and buccal swabs were collected for further analysis. Mass spectrometry-based proteomics was conducted on epithelial cells obtained from buccal swabs to evaluate protein expression level. Lasso statistical methods were conducted to study the association between protein abundance and infants' NNNS summary scores. Multiple linear regression and Gene Ontology (GO) enrichment analyses were performed to examine how clinical characteristics and neurodevelopmental outcomes may be associated with protein levels and underlying molecular pathways. Results During NICU hospitalization, preterm premature rupture of membrane (PPROM) were negatively associated with neurobehavioral outcomes. The protein functions including leptin receptor binding activity, glutathione disulfide oxidoreductase activity and response to oxidative stress, lipid metabolism, phosphate and proton transmembrane transporter activity were negatively associated with neurobehavioral outcomes, in the contrast, cytoskeletal regulation, epithelial barrier and protection function were found to be associated with the optimal neurodevelopmental outcomes. In addition, mitochondrial function associated proteins including SPRR2A, PAIP1, S100A3, MT-CO2, PiC, GLRX, PHB2, and BNIPL-2 demonstrated positive association with favorable neurodevelopmental outcomes, while proteins of ABLIM1, UNC45A, Keratins, MUC1, and CYB5B showed positive association with adverse neurodevelopmental outcomes. Conclusion Mitochondrial function-related proteins were observed to be associated with early life pain/stress and neurodevelopmental outcomes in infants. Large-scale studies with longitudinal datasets are warranted. Buccal proteins could be used to predict potential neurobehavioral outcomes.

Obesity Differs from Diabetes Mellitus in Antibody and T Cell Responses Post COVID-19 Recovery.

Obesity and type 2 diabetes (DM) are risk factors for severe COVID-19 outcomes, which disproportionately affect South Asian populations. This study aims to investigate the humoral and cellular immune responses to SARS-CoV-2 in adult COVID-19 survivors with obesity and DM in Bangladesh. In this cross-sectional study, SARS-CoV-2-specific antibody and T cell responses were investigated in 63 healthy and 75 PCR-confirmed COVID-19 recovered individuals in Bangladesh, during the pre-vaccination first wave of the COVID-19 pandemic in 2020. In COVID-19 survivors, SARS-CoV-2 infection induced robust antibody and T cell responses, which correlated with disease severity. After adjusting for age, sex, DM status, disease severity, and time since onset of symptoms, obesity was associated with decreased neutralising antibody titers, and increased SARS-CoV-2 spike-specific IFN-γ response along with increased proliferation and IL-2 production by CD8+ T cells. In contrast, DM was not associated with SARS-CoV-2-specific antibody and T cell responses after adjustment for obesity and other confounders. Obesity is associated with lower neutralising antibody levels and higher T cell responses to SARS-CoV-2 post COVID-19 recovery, while antibody or T cell responses remain unaltered in DM.

Regioselective Brønsted acid catalyzed ring opening of aziridines by phenols and thiophenols; a gateway to access functionalized indolines, indoles, benzothiazines, dihydrobenzo-thiazines, benzo-oxazines and benzochromenes.

Brønsted acid catalyzed regioselective ring opening of aziridines by phenols and thiophenols have been reported. Involvement of a series of aziridines with a range of phenols and thiophenols offer the generality of the reported protocol. Completion of the reaction at room temperature within very short time brings the uniqueness of the developed technique. To emphasis on the application of the developed methodology, the products have been used for the further synthesis of a range of useful and novel heterocyclic molecules such as indolines, indoles, benzothiazines, dihydrobenzothiazines, benzo-oxazines and benzochromenes.

Brønsted acid-catalyzed regioselective ring opening of 2H-azirines by 2-mercaptopyridines and related heterocycles; one pot access to imidazo[1,2-a]pyridines and imidazo[2,1-b]thiazoles.

A catalytic and versatile synthetic method for the synthesis of imidazo[1,2-a]pyridines has been developed. Brønsted acid-catalysis plays a major role in the regioselective ring opening of 2H-azirines. Nucleophilic attack via the N-centre of mercaptopyridines and their analogues, followed by cyclisation by cleaving the C-S bond, allowed a library of imidazo[1,2-a]pyridines and related heterocycles to be built. The reaction protocol has been applied to various 2H-azirines, 2-mercaptopyridines, and thiazole-2-thiols, illustrating the generality of reaction conditions. The practical applications include the synthesis of pharmaceuticals, such as anti-tumor agents. This study introduces a novel approach to the synthesis of functional molecules with extensive potential.

Replica symmetry breaking in a colloidal plasmonic random laser with gold-coated triangular silver nanostructures.

Plasmonic random lasers have drawn significant attention recently due to their versatility, low threshold, and the possibility of achieving tunable and coherent/incoherent outputs. However, in this Letter, the phenomenon of replica symmetry breaking is reported in intensity fluctuations of a rarely used colloidal plasmonic random laser (RL) illumination. Triangular nanosilver scatter particles produced incoherent RL action when used in a dimethylformamide (DMF) environment in a Rhodamine-6G gain medium. The use of gold-coated triangular nanosilver as the scatterer in place of triangular nanosilver offered a dual contribution of scattering and lower photo-reabsorption, which caused a reduction in the lasing threshold energy of 39% compared to that obtained with the latter. Further, due to its long-term photostability and chemical properties, a phase transition from the photonic paramagnetic to the glassy phase is observed experimentally in the RL system used. Interestingly, the transition occurs at approximately the lasing threshold value, which is a consequence of stronger correlation of modal behaviors at high input pump energies.

Regioselective Transition Metal-Free Catalytic Ring Opening of 2H-Azirines by Phenols and Naphthols; One-Pot Access to Benzo- and Naphthofurans.

Benzofuran and naphthofuran derivatives are synthesized from readily available phenols and naphthols. Regioselective ring openings of 2H-azirine followed by in situ aromatization using a catalytic amount of Brønsted acid have established the novelty of the methodology. The involvement of a series of 2H-azirines with a variety of phenols, 1-naphthols, and 2-naphthols showed the generality of the protocol. In-depth density functional theory calculations revealed the reaction mechanism with the energies of the intermediates and transition states of a model reaction. An alternate pathway of the mechanism has also been proposed with computer modeling.

(3 + 2) cycloaddition of 2-alkoxynaphthalenes with azaoxyallyl cations: access to benzo[e]indolones.

A reaction between 2-alkoxynaphthalene and an in situ formed azaoxyallyl cation has been reported under ambient reaction conditions. The (3 + 2) cycloaddition reaction followed by aryl C-OMe/C-OEt bond cleavage produces a variety of benzo[e]indolone derivatives. Based on the isolated intermediate from the control experiment and previous results, a possible mechanism has been drawn. Reduction of the N-O bond of the benzo[e]indolone derivative manifests the possibility of further functionalization of the products towards biologically important heterocyclic molecules.

Arsenic exposure during pregnancy and postpartum maternal glucose tolerance: evidence from Bangladesh.

BACKGROUND: Arsenic exposure has been associated with gestational diabetes mellitus. However, the extent to which arsenic exposure during pregnancy is associated with postpartum glucose intolerance is unknown. METHODS: We studied 323 women in Bangladesh. We assessed arsenic exposure in early pregnancy via toenail and water samples. We measured fasting glucose and insulin in serum at a mean (SD) of 4.0 (3.5) weeks post-delivery. We ran covariate-adjusted, linear regression models to examine associations of arsenic concentrations with HOMA-IR, a marker of insulin resistance, and HOMA-ß, a marker of beta cell function. RESULTS: Median (IQR) arsenic concentration was 0.45 (0.67) µg/g in toenails and 2.0 (6.5) µg/L in drinking water. Arsenic concentrations during pregnancy were not associated with insulin resistance or beta cell function postpartum. HOMA-IR was 0.07% (- 3.13, 3.37) higher and HOMA-ß was 0.96% (- 3.83, 1.99) lower per IQR increment in toenail arsenic, but effect estimates were small and confidence intervals crossed the null. CONCLUSIONS: Although arsenic exposure during pregnancy has been consistently associated with gestational diabetes mellitus, we found no clear evidence for an adverse effect on postpartum insulin resistance or beta cell function.

Unusual higher-order nonlinear optical properties in Au-coated triangular Ag-Au nanostructures.

Here, we report hitherto unobserved local field (LF)-assisted pump wavelength-dependent nonlinear optical (NLO) effects of three-photon (3PA)-induced four-photon absorption (4PA) at 532 nm and two-photon-induced 3PA at 730 nm in triangular-shaped core-shell Ag-Au nanoparticles (TrAg@Au) by femtosecond Z-scan. The shell thickness-dependent enhancement in the LF is observed by a COMSOL simulation. The intensity-dependent interplay between saturable and reverse-saturable absorptions along with switching of nonlinear (NL) phase is reported at 730 nm, showing the superiority of TrAg@Au in optical switching (OS). The optical limiting (OL) threshold (Fth) of 5.9(6.5)mJ/cm2 at 730 (532) nm boost their potential over benchmarked materials.

Enhanced biodegradation of total petroleum hydrocarbons by implementing a novel two-step bioaugmentation strategy using indigenous bacterial consortium.

In the present study, a two-step bioaugmentation strategy (TSBS) was implemented by using indigenous bacterial consortium to enhance the degradation of total petroleum hydrocarbons (TPH) from petroleum refinery sludge (PRS). A bacterial consortium was developed using four indigenous isolated strains, Dietzia sp. IRB191, Dietzia sp. IRB192, Staphylococcus sp. BSM19 and Stenotrophomonas sp. IRB19 from PRS. The optimum conditions of pH, temperature, and sludge concentration were 7, 34 °C, and 2% (w/v), respectively, for maximum TPH degradation, obtained using one variable at a time approach. Under the optimal culture conditions, the developed consortium was inoculated twice to the culturing medium, at the beginning (0th day) and again on the 10th day for implementing a novel TSBS. The maximum TPH degradation of 91.5 ± 2.28% was found with TSBS, which was 1.18 times higher than that of SSBS (77.3 ± 2.6%) in 15 days of incubation. GC-FID study also confirmed that the TPH present in the PRS was effectively degraded by the bacterial consortium with TSBS. The TPH degradation by using TSBS proceeded according to the first-order kinetics with a rate constant of 0.155 d-1. Hence, biodegradation using a TSBS can be considered an effective and eco-friendly process for safe disposal of petroleum refinery sludge.

Motivation for adherence to antiretroviral therapy by transgender people living with hiv - A study in West Bengal, India.

The introduction of antiretroviral therapy (ART) has substantially improved the survival of persons infected with HIV. In India, the aggregated HIV prevalence among transgender (TG) community was found 7.5%. West Bengal, with over 30,000 TG population recorded HIV prevalence of 4.8%. The qualitative study was conducted in 2019 with the objective to explore the motivating factors for adherence to ART treatment among TG people living with HIV (PLHIV) in an ART center. Respondents were motivated PLHIVs on ART with suitable treatment adherence recorded. Data were inductively analyzed, using thematic analysis, to identify themes central to ART adherence. Five themes emerged with prime acknowledgment of respondents that ART medication is lifelong for their survival with receiving support. Notwithstanding the chronic nature of the disease, TG PLHIV patient stands a better chance of maintaining treatment adherence if they are involved in treatment plans with their community-based members' helping as peer navigators.

HIV Risk profile and its socio-demographic correlates among long-distance truckers in West Bengal, India: Evidence from national HIV sentinel surveillance 2017.

BACKGROUND: Long-distance truckers (LDTs) belong to a special sentinel group with potentially high risk of acquisition of HIV owing to their high mobility, sociodemographic vulnerability, and high-risk behaviors. OBJECTIVE: The objective is to estimate the prevalence of HIV and identifies its sociodemographic correlates among a representative population of LDTs in West Bengal, India. METHODS: Between May and July 2017, HIV Sentinel Surveillance (HSS) was conducted in West Bengal by the National AIDS Control Organization. A total of 749 LDTs were recruited for the study, were interviewed, and tested for HIV. Descriptive and logistic regression analysis of socio-demographics, sexual risk behavior, and HIV serostatus were performed using SAS 9.3.2. RESULTS: The prevalence of HIV among LDT was 1.2% (95% confidence interval [CI] = 0.4-2.0). Mean age was 32.8 years (standard deviation 8.5), 77.1% were currently married, 89.9% were literate, 85.7% visited HSS site for collecting condoms or seeking medical care and treatment, 53.1% were rural residents, 86.7% had sex at least once with a female partner other than wife in the past 6 months, 2.7% had sex with a male partner and 1.7% injected drugs for recreational purpose. Higher age (odds ratio [OR] = 1.1 [95% CI = 1.0-1.1]), literate (OR = 0.3 [95% CI = 0.1-0.9]), visiting HSS sites for collecting condoms or seeking medical care and treatment (adjusted OR [AOR] = 0.2 [95% CI = 0.1-0.6]), rural residence (OR = 0.2 [95% CI = 0.1-0.3]) and duration of stay in home (AOR = 1.3 [95% CI = 1.1-1.5]) were found to be significant predictors of having sex with a female partner other than wife. CONCLUSION: High HIV burden calls for urgency in the implementation of targeted intervention to minimize HIV risk among LDTs in West Bengal to fight against HIV/AIDS.

Human immunodeficiency virus prevalence and high-risk behavior of home-based and nonhome-based female sex workers in three high-prevalent North-Eastern States of India.

BACKGROUND: Female sex workers (FSWs) have been identified as an important target group for human immunodeficiency virus (HIV)/sexually transmitted infections prevention. OBJECTIVES: This study aimed to describe sociodemographic and sex work characteristics and to identify the risk factors for HIV infection with special focus on the variations between home-based (HB) and non-HB (NHB) FSWs in three high-prevalent North-Eastern states of India: Manipur, Mizoram, and Nagaland. METHODS: Data from the National Integrated Bio-Behavioural Surveillance (IBBS) conducted in India during 2014-2015 were utilized in the study. IBBS is a quantitative survey conducted among identified high risk sub within India. Logistic regression analyses were performed using SAS 9.3.2 to determine the distribution and associations of sociodemographics and risk behaviors with HIV seropositivity of HB and NHB FSWs. RESULTS: HIV prevalence was found higher among NHB FSWs compared to HB FSW (7.3% vs. 4.6%). The proportions of FSW among HB (66.7%) were in sex work for longer duration are significantly higher than for NHB (60.2%) while risk of HIV infection due to injecting drug use was higher in NHB FSW (11.7% vs. 8.7%). Reference to FSW who were currently married, those who were widowed/divorced/separated had 2.73-fold risk of HIV. FSW who did not have any other income source were associated with 1.73 times more risk of HIV infection. Injecting drugs user among FSW respondents had four times higher likelihood to be HIV positive. CONCLUSION: A substantial proportion of NHB FSWs is mobile in nature. Targeted interventions are required urgently to minimize HIV risk among those FSWs especially the widowed/divorced/separated, sex work is only income source and who used injecting drugs for nonmedical purpose.

Variation in injecting drug use behavior across different North-eastern States in India.

Prevalence of adult HIV infection in India is still high in certain North-eastern (NE) states, particularly among injecting drug users (IDUs). This study aims at exploring IDU behavior profile and their variation across the different states of NE region, India. Data were drawn from a population-based, cross-sectional survey of IDU in the integrated bio-behavioral surveillance from 2014 to 2015. A total of 4272 IDUs from four states (Manipur, Meghalaya, Mizoram, and Nagaland) aged ≥15 years were interviewed. Descriptive analysis was conducted to identify the variation in demographic and IDU behavior across four states. Youth predominance in Mizoram was evident by the mean age of initiation <18 years; 74% and 65% had the first exposure of any drug and injecting drug in <20 years. In Manipur and Nagaland, 60% and 49% of IDUs, respectively, were ≥30 years of age. These specific age groups may be targeted for IDU risk mitigation addressing the state-specific determinants.

Lewis Acid Catalyzed Nucleophilic Ring Opening and 1,3-Bisfunctionalization of Donor-Acceptor Cyclopropanes with Hydroperoxides: Access to Highly Functionalized Peroxy/(α-Heteroatom Substituted)Peroxy Compounds.

The Lewis acid catalyzed ring opening reaction of Donor-Acceptor (D-A) cyclopropanes with alkyl hydroperoxides is reported to furnish various peroxycarbonyls and 1,3-haloperoxygenated compounds in good to excellent yields. This method adds another instance to scarcely reported noncyclilizing 1,3-bisfunctionalization of D-A cyclopropanes with two different functional groups and relies on the dual role of peroxide as nucleophile and oxidant through an orchestrated reaction sequence. The products obtained, including α-heterosubstituted peroxy compounds, are amenable to useful synthetic elaboration.

Homeostatic nuclear RAGE-ATM interaction is essential for efficient DNA repair.

The integrity of genome is a prerequisite for healthy life. Indeed, defects in DNA repair have been associated with several human diseases, including tissue-fibrosis, neurodegeneration and cancer. Despite decades of extensive research, the spatio-mechanical processes of double-strand break (DSB)-repair, especially the auxiliary factor(s) that can stimulate accurate and timely repair, have remained elusive. Here, we report an ATM-kinase dependent, unforeseen function of the nuclear isoform of the Receptor for Advanced Glycation End-products (nRAGE) in DSB-repair. RAGE is phosphorylated at Serine376 and Serine389 by the ATM kinase and is recruited to the site of DNA-DSBs via an early DNA damage response. nRAGE preferentially co-localized with the MRE11 nuclease subunit of the MRN complex and orchestrates its nucleolytic activity to the ATR kinase signaling. This promotes efficient RPA2S4-S8 and CHK1S345 phosphorylation and thereby prevents cellular senescence, IPF and carcinoma formation. Accordingly, loss of RAGE causatively linked to perpetual DSBs signaling, cellular senescence and fibrosis. Importantly, in a mouse model of idiopathic pulmonary fibrosis (RAGE-/-), reconstitution of RAGE efficiently restored DSB-repair and reversed pathological anomalies. Collectively, this study identifies nRAGE as a master regulator of DSB-repair, the absence of which orchestrates persistent DSB signaling to senescence, tissue-fibrosis and oncogenesis.

Modeling and optimization of process variables for HCl gas removal by response surface methodology.

In the present article, optimization of process variables has been done to maximize the removal efficiency of toxic HCl gas in a submerged self-priming venturi scrubber. Response surface methodology with central composite design has been chosen to predict the effect of process variables on the removal efficiency. A quadratic equation was found from this study to predict the removal efficiency and from the ANOVA test, the significance of process variables was evaluated. Regression analysis confirmed the suitability of the developed model by the higher R2 square value (0.9717). Optimum conditions were obtained as 55.18 m s-1 of throat gas velocity, 405.10 ppm of inlet HCl concentration and 0.0038 N of NaOH concentration in scrubbing liquid to achieve 90.80% of the HCl removal efficiency.

Neutrophil elastase and myeloperoxidase mRNA expression in overweight and obese subjects.

Neutrophil elastase and myeloperoxidase enzymes have been implicated in high-fat diet-induced obesity, insulin resistance (IR) and atherosclerosis in animal models. The aim of the present study was to explore neutrophil elastase and myeloperoxidase mRNA expressions in the peripheral blood leukocytes (PBL) in overweight and obese subjects, and to correlate those mRNA expressions with BMI, IR and cardiovascular biomarkers. In this cross-sectional study, 74 apparently healthy subjects including 22 lean, 27 overweight and 25 obese subjects were recruited. Cardiovascular and metabolic biomarkers were evaluated from fasting blood samples. The mRNA levels of neutrophil elastase and myeloperoxidase genes in the PBL were quantified by real-time PCR. Compared to lean group, the overweight and obese groups showed significant upregulation of both neutrophil elastase (p < 0.001) and myeloperoxidase (p < 0.03) mRNA expressions in the PBL. But no difference was found between overweight and obese groups. The neutrophil elastase and myeloperoxidase mRNA levels showed significant positive correlation with BMI, serum triglyceride, atherogenic index of plasma and 10-year risk of developing cardiovascular disease. But no correlation was found with glucose, insulin or IR. It was concluded that the neutrophil elastase and myeloperoxidase genes are up-regulated in both overweight and obese subjects and are associated with BMI and markers of cardiovascular disease.

Serine 307 on insulin receptor substrate 1 is required for SOCS3 and TNF-α signaling in the rMC-1 cell line.

PURPOSE: To establish the key insulin receptor substrate 1 (IRS-1) structural elements required in this insulin regulatory pathway, we investigated the effects of substituting alanine for serine 307 in IRS-1 on the ability of tumor necrosis factor-α (TNF-α) and a related mediator, suppressor of cytokine signaling 3 (SOCS3), to phosphorylate IRS-1 and regulate insulin signaling in the rat retinal Müller cell (rMC-1) cell line. METHODS: rMC-1 cells were grown in normal (5 mM) or high (25 mM) glucose medium and transfected with either normal IRS-1(Ser307)plasmid or a mutated IRS-1(Ser307Ala) plasmid. Cells were also treated with recombinant TNF-α or SOCS3 to induce increased levels of these proteins. RESULTS: In cells with IRS-1(Ser307Ala), TNF-α and SOCS3 failed to phosphorylate IRS-1. Likewise, resulting downstream effects, including changes in phosphorylation of insulin receptor(Tyr960), antiapoptotic Akt phosphorylation, and proapoptotic cleavage of caspase 3 were also blocked. We also report for the first time that SOCS3 and TNF-α are reciprocally stimulatory leading to a mutual enhancement of levels of both factors, thus forming a potential positive feedback loop that contributes to insulin receptor resistance. CONCLUSIONS: Increases in TNF-α and SOCS3 are triggered by high glucose and through reciprocal stimulation of expression of these two factors, which in turn could be major drivers of insulin resistance and related cell death. The demonstration that a single phosphorylation site is key for these pathways suggests that drugs targeted to this site might be effective in protecting against diabetic damage to the retina.