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Background: Antemortem diagnosis of cerebral toxoplasmosis, the second most common opportunistic infection (OI) in HIV-infected individuals in developing countries is a challenge. Materials and Methods: Toxoplasma gondii (T.gondii) -specific serology and nested polymerase chain reaction (nPCR) were evaluated in sera and ventricular/lumbar cerebrospinal fluid (CSF) of 22 autopsy confirmed cases of cerebral toxoplasmosis with HIV and 17 controls. Frequency of concomitant T.gondii infection was investigated in 17 cases of HIV-associated tuberculous meningitis (TBM). Results: The sensitivity, specificity, and positive and negative predictive values of T. gondii IgG on CSF (ventricular and lumbar) and sera was 100% in histology proven cerebral toxoplasmosis (concentrations: 258 ± 50, 231 ± 36, and 646 ± 243 IU/mL, respectively); majority (94%) being high avidity type, suggesting reactivation/reinfection. The sensitivity of B1 nPCR was 100% on ventricular CSF, whereas it was only 77% on lumbar CSF. Based on histology, nPCR, and IgG serology, T. gondii co-infection with TBM was observed in 65% (11/17) of cases. Discussion and Conclusion: CSF IgG serology and nPCR are tests with high sensitivity and specificity for the diagnosis of cerebral toxoplasmosis. TBM and cerebral toxoplasmosis can coexist and should be considered in the background of HIV infection in developing countries.

Background: The human polyoma virus, also known as the JC virus (JCV), replicates predominantly in the oligodendrocytes, the myelin producing cells in the central nervous system and results in the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML) especially in immunosuppressed patients with AIDS. Several investigators have also documented the presence of the viral genome and early and late antigens in a variety of brain tumors particularly in medulloblastomas, gliomas and ependymomas. Reports also indicate the presence of JCV in patients with colon cancer. The T antigen of JCV has been postulated to have oncogenic potential as substantiated by animal experiments. Although JCV infects 80% of the population, there are scant epidemiological studies regarding JCV from India. There are also reports of the low prevalence of PML in patients with AIDS from India and Africa. Aim: This study was undertaken to investigate if Indian children with medulloblastomas also show evidence of JCV. Methods: Twenty-two consecutive cases of medulloblastomas were investigated for the presence of T antigen and agnoprotein of JCV in biopsy specimens by immunohistochemistry. Antibodies to the agnoprotein antigen raised in rabbits and a monoclonal antibody against SV40 T antigen raised in mice that cross-reacts with JCV T antigen were used. Results: Out of 22 patients, 4 had desmoplastic tumors while the rest had classical tumors. All children were below the age of 10. Results indicate that while PML tissues showed consistent immunostaining both with antibody to T antigen and agnoprotein antibody, none of the tumors showed any positive staining for JC viral antigens. Conclusion: JCV antigens could not be detected by immunohistochemistry in the tumor tissues of Indian children with medulloblastomas.

Abstract Background Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS). It involves damage to the myelin sheath surrounding axons and to the axons themselves. MS most often presents with a series of relapses and remissions but then evolves over a variable period of time into a slowly progressive form of neurological dysfunction termed secondary progressive MS (SPMS). The reasons for this change in clinical presentation are unclear. The absence of a diagnostic marker means that there is a lag time of several years before the diagnosis of SPMS can be established. At the same time, understanding the mechanisms that underlie SPMS is critical to the development of rational therapies for this untreatable stage of the disease. Results Using high performance liquid chromatography-coupled mass spectrometry (HPLC); we have established a highly specific and sensitive selected reaction monitoring (SRM) assay. Our multiplexed SRM assay has facilitated the simultaneous detection of surrogate peptides originating from 26 proteins present in cerebrospinal fluid (CSF). Protein levels in CSF were generally ~200-fold lower than that in human sera. A limit of detection (LOD) was determined to be as low as one femtomol. We processed and analysed CSF samples from a total of 22 patients with SPMS, 7 patients with SPMS treated with lamotrigine, 12 patients with non-inflammatory neurological disorders (NIND) and 10 healthy controls (HC) for the levels of these 26 selected potential protein biomarkers. Our SRM data found one protein showing significant difference between SPMS and HC, three proteins differing between SPMS and NIND, two proteins between NIND and HC, and 11 protein biomarkers showing significant difference between a lamotrigine-treated and untreated SPMS group. Principal component analysis (PCA) revealed that these 26 proteins were correlated, and could be represented by four principal components. Overall, we established an efficient platform to develop and verify protein biomarkers in CSF, which can be easily adapted to other proteins of interest related to neurodegenerative diseases. Conclusions A highly specific and sensitive multiplex SRM-MS assay was established for development and verification of CSF protein biomarkers in SPMS. Five proteins were found to be expressed significantly differently between the three cohorts, SPMS, NIND and HC and 11 proteins associated with lamotrigine treatment, which we expect will further our current understanding of SPMS disease pathology and/or therapeutic intervention.

Abstract Methamphetamine (METH) abuse has reached epidemic proportions, and it has become increasingly recognized that abusers suffer from a wide range of neurocognitive deficits. Much previous work has focused on the deleterious effects of METH on mature neurons, but little is known about the effects of METH on neural progenitor cells (NPCs). It is now well established that new neurons are continuously generated from NPCs in the adult hippocampus, and accumulating evidence suggests important roles for these neurons in hippocampal-dependent cognitive functions. In a rat hippocampal NPC culture system, we find that METH results in a dose-dependent reduction of NPC proliferation, and higher concentrations of METH impair NPC survival. NPC differentiation, however, is not affected by METH, suggesting cell-stage specificity of the effects of METH. We demonstrate that the effects of METH on NPCs are, in part, mediated through oxidative and nitrosative stress. Further, we identify seventeen NPC proteins that are post-translationally modified via 3-nitrotyrosination in response to METH, using mass spectrometric approaches. One such protein was pyruvate kinase isoform M2 (PKM2), an important mediator of cellular energetics and proliferation. We identify sites of PKM2 that undergo nitrotyrosination, and demonstrate that nitration of the protein impairs its activity. Thus, METH abuse may result in impaired adult hippocampal neurogenesis, and effects on NPCs may be mediated by protein nitration. Our study has implications for the development of novel therapeutic approaches for METH-abusing individuals with neurologic dysfunction and may be applicable to other neurodegenerative diseases in which hippocampal neurogenesis is impaired.

Abstract Background HIV Associated Dementia (HAD) is a common complication of human immunodeficiency virus (HIV) infection that erodes the quality of life for patients and burdens health care providers. Intravenous drug use is a major route of HIV transmission, and drug use is associated with increased HAD. Specific proteins released as a consequence of HIV infection (e.g., gp120, the HIV envelope protein and Tat, the nuclear transactivating protein) have been implicated in the pathogenesis of HAD. In primary cultures of human fetal brain tissue, subtoxic doses of gp120 and Tat are capable of interacting with a physiologically relevant dose of cocaine, to produce a significant synergistic neurotoxicity. Using this model system, the neuroprotective potential of gonadal steroids was investigated. Results 17β-Estradiol (17β-E2), but not 17α-estradiol (17α-E2), was protective against this combined neurotoxicity. Progesterone (PROG) afforded limited neuroprotection, as did dihydrotestosterone (DHT). The efficacy of 5α-testosterone (T)-mediated neuroprotection was robust, similar to that provided by 17β-E2. In the presence of the specific estrogen receptor (ER) antagonist, ICI-182,780, T's neuroprotection was completely blocked. Thus, T acts through the ER to provide neuroprotection against HIV proteins and cocaine. Interestingly, cholesterol also demonstrated concentration-dependent neuroprotection, possibly attributable to cholesterol's serving as a steroid hormone precursor in neurons. Conclusion Collectively, the present data indicate that cocaine has a robust interaction with the HIV proteins gp120 and Tat that produces severe neurotoxicity, and this toxicity can be blocked through pretreatment with ER agonists.

Abstract Background Human immunodeficiency virus (HIV) infection continues to increase at alarming rates in drug abusers, especially in women. Drugs of abuse can cause long-lasting damage to the brain and HIV infection frequently leads to a dementing illness.To determine how these drugs interact with HIV to cause CNS damage, we used an in vitro human neuronal culture characterized for the presence of dopaminergic receptors, transporters and estrogen receptors. We determined the combined effects of dopaminergic drugs, methamphetamine, or cocaine with neurotoxic HIV proteins, gp120 and Tat. Results Acute exposure to these substances resulted in synergistic neurotoxic responses as measured by changes in mitochondrial membrane potential and neuronal cell death. Neurotoxicity occurred in a sub-population of neurons. Importantly, the presence of 17beta-estradiol prevented these synergistic neurotoxicities and the neuroprotective effects were partly mediated by estrogen receptors. Conclusion Our observations suggest that methamphetamine and cocaine may affect the course of HIV dementia, and additionally suggest that estrogens modify the HIV-drug interactions.

Nitrate and fluoride are two of the most prevalent pollutants in drinking water and exposure to their high concentrations could cause methemoglobinemia and fluorosis. This study attempted to evaluate the groundwater quality (pH: 4.4-9) from a relatively understudied part of the southwestern coast in India (i.e., Alappuzha, Kerala state) and assessed the associated health risks from exposures to nitrate (0.2-5.8 mg/l) and fluoride (0.2-1.9 mg/l) present in the groundwater. Pollution index (PIG: 0.35-5.43) grouped about 21% samples in high pollution and very high pollution categories because of fluoride content above the WHO guidelines. The total hazard index (THI) for adult male (0.17-1.70; average: 0.75), adult female (0.19-1.85; average: 0.81) and children (0.35-3.40; average: 1.50) suggested more non-carcinogenic risks for children from 41.6% samples compared to adult male and female from 33.3% samples in the absence of any mitigation measure. These results provide additional data from the country with highest population and the largest groundwater use in the context of sustainability in availability and supply of groundwater under the increasing risks of population growth, climate change and industrial development., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr.S.Selvam reports administrative support was provided by V.O.Chidambaram College. Dr.S.Selvam reports a relationship with V.O.Chidambaram College that includes: employment. Dr.S.Selvam has patent pending to Nil. No., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The present study has been carried out to assess the quality of groundwater and surface water resources of Thettiyar watershed, Kerala, India. Sixty-six water samples were collected during pre-monsoon (April, 2019) and monsoon (July, 2019) season, and analyzed for pH, electrical conductivity (EC), total dissolved solids (TDS), total hardness and major cations and anions and microbiological parameters as well. According to the piper diagram's plot, Ca and Mg dominate over Na among the cations, and Cl is the most prevalent anion in groundwater throughout both the studied seasons. The hydrochemical analysis of water samples revealed that all the parameters are within the permissible limit except for pH. For microbiological analysis, the samples were tested for total coliform and fecal coliform. Most of the groundwater samples collected have higher total coliform and fecal coliform (E. coli) content than the recommended count by BIS (2012). The pre-monsoon surface water samples owned a maximum number of 3700 cfu/100 ml (TNTC-too numerous to count) of total coliform and 1400 cfu/100 ml (TNTC) of fecal coliform. In monsoon, the number of total coliform and fecal coliform has increased to 3800 cfu/100 ml and 1900 cfu/100 ml respectively. E. coli and total coliform are effectively correlated with each other in both seasons, in accordance with the statistical study. Domestic, sewage dump, and other household wastes are the main sources of bacterial contamination in the study area, which in turn nourishes contaminant organisms. According to the results, the government or municipality should implement an appropriate system for managing solid waste and should take all necessary measures to clean up the study area., (© 2023. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Bacterial infection remains a great challenge in wound healing, especially in chronic wounds. Multidrug-resistant organisms are increasing in acute and chronic wound infections, which compromise the chance of therapeutics. Resistance to conventional antibiotics has created an urge to study new approach/system that can effectively control wound infection and enhance healing. Wound cover/dressing must exhibit biocompatibility and effectiveness in reducing bioburden at the wound site. Collagen, a natural biopolymer, possesses advantages over synthetic and other natural materials due to its unique biological properties. It can act as an excellent wound dressing and controlled drug delivery system. Currently, antiseptic agents such as silver, iodine, and polyhexamethylene biguanide (PHMB)-incorporated scaffolds have become widely accepted in chronic wound healing. In this study, PHMB-incorporated collagen scaffold has been prepared and characterized using Fourier transform infrared spectroscopy (FTIR), circular dichroism (CD), and differential scanning calorimetry (DSC), which showed retention of collagen nativity and integration of PHMB. The scanning electron microscopy (SEM) analysis revealed the porous structures of scaffolds. The cytotoxicity analysis showed PHMB is nontoxic at the concentration of 0.01% (wt/wt). The agar diffusion test and bacterial adhesion study demonstrated the effectiveness of PHMB-incorporated collagen scaffold against both gram positive and negative strains. This study concludes that PHMB-incorporated collagen scaffold could have the potential for infected wound healing., (© 2021 Wiley Periodicals LLC.)

Cardiac mesenchymal cells (CMCs) are a promising cell type that showed therapeutic potential in heart failure models. The analysis of the underlying mechanisms by which the CMCs improve cardiac function is on track. This study aimed to investigate the expression of N-Cadherin, a transmembrane protein that enhances cell adhesion, and recently gained attention for differentiation and augmentation of stem cell function. The mouse CMCs were isolated and analyzed for the mesenchymal markers using flow cytometry. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blot analysis were used to assess the expression of N-Cadherin along with its counteracting molecule E-Cadherin and their regulator Zeb1 in CMCs and dermal fibroblast. The expression level of miR-200c and miR-429 was analyzed using miRNA assays. Transient transfection of miR-200c followed by qRT-PCR, western blot analysis, and immunostaining was done in CMCs to analyze the expression of Zeb1, N-Cadherin, and E-Cadherin. Flow cytometry analysis showed that CMCs possess mesenchymal markers and absence for hematopoietic and immune cell markers. Increased expression of N-Cadherin and Zeb1 in CMCs was observed in CMCs at both RNA and protein levels compared to fibroblast. We found significant downregulation of miR-200c and miR-429 in CMCs. The ectopic expression of miR-200c in CMCs significantly downregulated Zeb1 and N-Cadherin expression. Our findings suggest that the significant downregulation of miR-200c/429 in CMCs maintains the expression of N-Cadherin, which may be important for its functional integrity., (© 2021 International Federation for Cell Biology.)

We assessed the groundwater quality in an industrial area (Tiruchendur Taluk) of Tamil Nadu state in coastal south India for human health risk from drinking as well as irrigation suitability by using the drinking water quality index (DWQI), irrigation factors (sodium adsorption ratio, sodium percentage, residual sodium carbonate and permeability index) and health hazard valuation (THQI- by consuming NO 3 - and F - ). About 57% of the samples represented Ca 2+ -Mg 2+ -Cl - -SO 4 2- facies and the anthropological unhygienic inputs elevated the salinity. Our results indicated that all the samples are unsuitable for drinking (DWQI up to 1063) and almost half of them are also unsuitable for irrigation due to sodium risk. Total hazard quotient index (THQI; HQ nitrate and HQ fluoride ) suggested the order of health risk as children > women > men with about 64%, 70% and 79% of the samples posing non-carcinogenic risks for men, women and children, respectively. Different mitigation measures and sustainable development should be enforced to minimize the health issues from contamination caused by industries, fertilizers in agro-fields and natural processes and reduce the sodium dominance in groundwater. The spatial distribution maps of this study could also be helpful in organization of proper treatment plans to provide safe and hygienic groundwater to the community., (Copyright © 2021 Elsevier Inc. All rights reserved.)

We assessed groundwater pollution index (GPI) and groundwater quality of coastal aquifers from Tiruchendur in South India for drinking and irrigation by evaluating the physico-chemical parameters of 35 samples of mainly Na-Cl type in an area of 470 km 2 with respect to the World Health Organization (WHO) standard as well as by estimating different indices such as total hardness (TH), sodium percentage (Na%), magnesium ratio (MR), Kelley's ratio index (KR), potential salinity (PS), Langelier saturation index (LSI), residual sodium carbonate (RSC), sodium adsorption rate (SAR), permeability index (PI), and the irrigation water quality index (IWQI). Minimal influence of aquifer lithology and the dominant influence of evaporation on groundwater chemistry reflected the semi-arid climate of the study area. Electrical conductivity (EC) of about 89% of the samples across 418 km 2 exceeded the permissible limit and Ca values of 74% of samples, however, remained within the allowable limit for drinking. More chloride was caused by influx of seawater and salt leaching and higher K was due to excessive fertilizer usage for agriculture. The spatial distribution map created using inverse distance weighting (IDW) method shows that the suitable groundwater is present close to the river basin. GPI values between 0.40 and 4.7, with an average of 1.5, classify insignificant pollution in 43% of the study region and the groundwater suitable for drinking purposes. In addition, 17% of the groundwater samples are also marginally suitable for drinking. The irrigation water quality indices provided contradictory assessments. Indices of TH, Na%, MR, PS, and LSI suggested 32-95% of the samples as unsuitable for irrigation, whereas the indices of RSC, SAR, and PI grouped 72-100% samples as permissible for irrigation. The IWQI map, however, indicated that the groundwater from more than half of the study area are not apt for irrigation and the groundwater of about one-third of the area could only be applied to salt-resistant plants.