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Objectives: Although the advent of Combination Antiretroviral Therapy (cART) has greatly reduced the prevalence of HIV-Associated Dementia, the most severe form of HIV-Associated Neurocognitive Disorder (HAND), the incidence of the milder forms of HAND have risen. The explanations proposed include persistent central nervous system (CNS) viraemia and the neurotoxicity of chronic cART regimens. Nonetheless, controversies in HAND prevalence estimates, alongside a lack of consensus on the significance of CNS Penetration Effectiveness (CPE) have added to the complexity of elucidating the role of cART in HAND. The present review will evaluate the evidence underlying these explanations, as well as highlighting the need for improved trial designs and the incorporation of emerging biomarkers and neuroimaging tools., Methods: A review of the current literature investigating cART neurotoxicity, controversies in HAND prevalence estimates, CNS Penetration Effectiveness, and neuroprotective adjuvant therapies., Conclusions: Ultimately, the inadequacy of cART in achieving complete preservation of the CNS underscores the imminent need for neuroprotective adjuvant therapies, where the efficacy of combining multiple adjuvant classes presents a potential therapeutic frontier which must be interrogated., (© 2021 The Authors. HIV Medicine published by John Wiley & Sons Ltd on behalf of British HIV Association.)

Biological mass spectrometry has evolved as a core analytical technology in the last decade mainly because of its unparalleled ability to perform qualitative as well as quantitative profiling of enormously complex biological samples with high mass accuracy, sensitivity, selectivity and specificity. Mass spectrometry-based techniques are also routinely used to assess glycosylation and other post-translational modifications, disulfide bond linkage, and scrambling as well as for the detection of host cell protein contaminants in the field of biopharmaceuticals. The role of mass spectrometry in vaccine development has been very limited but is now expanding as the landscape of global vaccine development is shifting towards the development of recombinant vaccines. In this review, the role of mass spectrometry in vaccine development is presented, some of the ongoing efforts to develop vaccines for diseases with global unmet medical need are discussed and the regulatory challenges of implementing mass spectrometry techniques in a quality control laboratory setting are highlighted., (© 2018 The Authors. Mass Spectrometry Reviews Published by Wiley Periodicals, Inc.)

Objective: To investigate the association of newly identified genetic variants G>A (rs2285947) of the DNAH11 gene and G>A (rs2494938) of the LRFN2 gene with ovarian and breast cancers in women belonging to Jammu and Kashmir state, where the prevalence of ovarian and breast cancers is remarkably high in the population., Methods: A candidate gene prospective case-control association study design was adopted, in which 354 cases (219 cases of ovarian cancer and 135 cases of breast cancer) were histopathologically confirmed and 330 healthy controls matched for age and ethnicity were recruited. The details of cases and controls were also recorded in a predesigned pro forma after their written informed consent. Both variants were genotyped by TaqMan allele discrimination assay using real-time polymerase chain reaction. Logistic regression analysis was performed to estimate the corrected odds ratio (OR), confidence interval (CI), and level of significance (P value) for potential confounding factors., Results: The rs2285947 variant of DNAH11 was found to be significantly associated with both ovarian and breast cancers with adjusted ORs of 1.7 (95% CI 1.2-2.4; P=0.004) and 1.70 (95% CI 1.13-2.54; P=0.0009), respectively. However, no significant association of variant rs2494938 of LRFN2 was observed with ovarian cancer (estimated OR 0.9, 95% CI 0.6-1.4; P=0.919) or breast cancer (estimated OR 1.27, 95% CI 0.8-1.9; P=0.216)., Conclusions: The collected data proposed that the variant rs2285947 of DNAH11 gene is a potential risk factor for ovarian and breast cancers in the studied population., (© 2019 International Federation of Gynecology and Obstetrics.)

Our Fuzzy-Border (FB) continuum solvent model has been extended and modified to produce hydration parameters for small molecules using POlarizable Simulations Second-order Interaction Model (POSSIM) framework with an average error of 0.136 kcal/mol. It was then used to compute pK a shifts for carboxylic and basic residues of the turkey ovomucoid third domain (OMTKY3) protein. The average unsigned errors in the acid and base pK a values were 0.37 and 0.4 pH units, respectively, versus 0.58 and 0.7 pH units as calculated with a previous version of polarizable protein force field and Poisson Boltzmann continuum solvent. This POSSIM/FB result is produced with explicit refitting of the hydration parameters to the pK a values of the carboxylic and basic residues of the OMTKY3 protein; thus, the values of the acidity constants can be viewed as additional fitting target data. In addition to calculating pK a shifts for the OMTKY3 residues, we have studied aspartic acid residues of Rnase Sa. This was done without any further refitting of the parameters and agreement with the experimental pK a values is within an average unsigned error of 0.65 pH units. This result included the Asp79 residue that is buried and thus has a high experimental pK a value of 7.37 units. Thus, the presented model is capable or reproducing pK a results for residues in an environment that is significantly different from the solvated protein surface used in the fitting. Therefore, the POSSIM force field and the FB continuum solvent parameters have been demonstrated to be sufficiently robust and transferable. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Dried rhizome of Bergenia ligulata (pashanbhed) is commonly used as a traditional herbal medicine with a wide range of therapeutic applications including urolithiasis. Aqueous extract of B. ligulata was prepared through maceration followed by decoction (mother extract, 35.9% w/w). Further, polarity based fractions were prepared successively from mother extract which yielded 3.4, 2.9, 5.4, 7.5, and 11.3% w/w of hexane, toluene, dichloromethane (DCM), n -butanol, and water fractions, respectively. The in vitro, ex vivo, and real-time antiurolithiasis activity of mother extract and fractions were carried out using aggregation assay in synthetic urine and in rat plasma. The study revealed that DCM fraction has significantly ( p < 0.05) greater inhibitory potential than other fractions. Ethylene glycol in drinking water (0.75%, v/v) for 28 days was used for induction of urolithiasis and the curative effects of mother extract and DCM fraction were checked for the level of oxalate, calcium, creatinine, uric acid, and urea of both urine and serum. Treatment with mother extract and DCM fraction at a dose of 185 mg/kg and 7 mg/kg, respectively, in ethylene glycol induced rats resulted in a significant ( p < 0.05) decrease in serum and urine markers. Histological study revealed lower number of calcium oxalate deposits with minimum damage in the kidneys of mother extract and DCM fraction treated rats. This result provides a scientific basis for its traditional claims., Competing Interests: The authors wish to confirm that there is no known conflict of interests associated with this publication and there has been no significant financial support for this work that could have influenced its outcome.

We have computed pK(a) values for 11 substituted phenol compounds using the continuum Fuzzy-Border (FB) solvation model. Hydration energies for 40 other compounds, including alkanes, alkenes, alkynes, ketones, amines, alcohols, ethers, aromatics, amides, heterocycles, thiols, sulfides, and acids have been calculated. The overall average unsigned error in the calculated acidity constant values was equal to 0.41 pH units and the average error in the solvation energies was 0.076 kcal/mol. We have also reproduced pK(a) values of propanoic and butanoic acids within about 0.1 pH units from the experimental values by fitting the solvation parameters for carboxylate ion carbon and oxygen atoms. The FB model combines two distinguishing features. First, it limits the amount of noise which is common in numerical treatment of continuum solvation models by using fixed-position grid points. Second, it uses either second- or first-order approximation for the solvent polarization, depending on a particular implementation. These approximations are similar to those used for solute and explicit solvent fast polarization treatment which we developed previously. This article describes results of using the first-order technique. This approximation places the presented methodology between the Generalized Born and Poisson-Boltzmann continuum solvation models with respect to their accuracy of reproducing the many-body effects in modeling a continuum solvent., (Copyright © 2012 Wiley Periodicals, Inc.)

Objective: To investigate the involvement of the receptor gene for advanced glycation (RAGE), its ligand EN-RAGE, and COX-2 in endometriosis., Methods: The mRNA and protein expression of the corresponding genes were determined from endometriotic cells from 28 study patients and healthy endometrial stromal cells from 20 controls by semiquantitative RT-PCR and Western blot analysis, respectively, using beta-actin as an invariant control., Results: The expression of COX-2, RAGE, and EN-RAGE was significantly increased, as evidenced by the significantly greater mRNA and protein expression in the cells of the study patients (P<0.001). Previous treatment for endometriosis did not lessen mRNA and protein expression (P<0.001)., Conclusion: Our findings strengthen the hypothesis of an underlying inflammation in the pathophysiology of endometriosis and suggest exploring anti-inflammatory therapies as adjunct treatment., (Copyright 2010 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.)

The aims of this study were (i) to map the extent of all mental health placements in the independent sector, for adults of working age, and elderly people (excluding those with a diagnosis of dementia placed in Local Authority care homes), on a census date, across the areas in which the study was commissioned; (ii) to identify the characteristics of the population in placements; (iii) to explore some of the characteristics of the placements and the patterns of use within the private and voluntary sectors; and (iv) to identify the funding source of placements, and cost differences between the private and voluntary sector. The study took place in seven Strategic Health Authority areas, and information was sought from all Primary Care Trust and Social Services commissioners of mental health services, including regional secure commissioning teams, within those areas. A cross-sectional sample was used. Information was requested in relation to every individual meeting the inclusion criteria, placed in independent (private or voluntary) psychiatric hospitals, registered mental nursing homes and care homes on a specified study 'census date' of 28 June 2004 in six of the Strategic Health Authority areas, and 7 October 2004 in the seventh. Information was recorded on a standard questionnaire specifically designed for the study. Information was obtained on 3535 adults and 1623 elderly people in private or voluntary facilities. The largest groups of adults and elderly people had diagnoses of severe mental illnesses (42.1% and 30.5%, respectively), and placements were described as 'continuing care' or rehabilitation, with a 'niche' in specialist forensic care. Around four-fifths of units were in the private sector, which for adults was significantly more expensive than the voluntary sector. A large proportion of units (47.2% of adult placements and 59.3% of placements for elderly people) had only single placements from particular commissioning authorities, whilst others had large numbers, raising issues for effective commissioning. The distance of placements from patients' area of origin, is also an issue highlighted by the study. The study findings are discussed in relation to commissioning practice, and the development of the independent sector in mental health care.