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Background: Poorly managed post-operative pain can lead to complications and prolonged rehabilitation. Pain Management after ano-rectal surgery becomes important as it could hamper day to day activities, disturb sleep, alter appetite and bowel evacuations and decrease the quality of life. According to Acharya Sushrutha, pain (Shoola) cannot be produced without Vata dosha and Shoola (pain) is inevitable after Shastra (surgical) Karma (procedure) for which Basti (enema) is usually the management of choice. Rectal suppositories are one such dosage form that are extensively used in post-operative pain management especially after ano-rectal surgery. Materials and method: In the study, a total of 40 patients who fulfilled the inclusion criteria were randomly divided to two groups comprising of 20 patients each. Patients of Group A were treated with Gandhaka Rasayana rectal suppository and Group B were treated with Diclofenac Sodium rectal suppository for post-operative 5 days. Results: The overall comparative results revealed a statistically significant improvement of 85% in Group A and 80.39% in Group B. Gandhaka Rasayana which is Tridoshashamaka, Vatamaya Nivaraka (ameliorates diseases caused by Vata dosha), Agnivardhaka (improves appetite and metabolism) and Shoolahara (reduces pain) attains micro particle size with 88 Bhavana (trituration) that can be readily absorbed by the rectal mucosa to exhibit the required therapeutic action. Conclusion: The Bhavana Dravya (medium of trituration) used in the preparation of Gandhaka Rasayana have proven analgesic, anti-inflammatory, anti-bacterial action and is also said to promote wound healing. The present study reveals that there is significant effect of Gandhaka Rasayana rectal suppositories in managing post-operative pain of ano-rectal disorders.

The detection of HPV infection and microbial colonization in cervical lesions is currently done through PCR-based viral or bacterial DNA amplification. Our objective was to develop a methodology to expand the metaproteomic landscape of cervical disease and determine if protein biomarkers from both human and microbes could be detected in distinct cervical samples. This would lead to the development of multi-species proteomics, which includes protein-based lateral flow diagnostics that can define patterns of microbes and/or human proteins relevant to disease status. In this study, we collected both non-frozen tissue biopsy and exfoliative non-fixed cytology samples to assess the consistency of detecting human proteomic signatures between the cytology and biopsy samples. Our results show that proteomics using biopsies or cytologies can detect both human and microbial organisms. Across patients, Lumican and Galectin-1 were most highly expressed human proteins in the tissue biopsy, whilst IL-36 and IL-1RA were most highly expressed human proteins in the cytology. We also used mass spectrometry to assess microbial proteomes known to reside based on prior 16S rRNA gene signatures. Lactobacillus spp. was the most highly expressed proteome in patient samples and specific abundant Lactobacillus proteins were identified. These methodological approaches can be used in future metaproteomic clinical studies to interrogate the vaginal human and microbiome structure and metabolic diversity in cytologies or biopsies from the same patients who have pre-invasive cervical intraepithelial neoplasia, invasive cervical cancer, as well as in healthy controls to assess how human and pathogenic proteins may correlate with disease presence and severity., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier B.V.)

Nosocomial outbreaks of Burkholderia cepacia complex, transmitted through contaminated medical surfaces or equipment have been reported. Pulsed-field Gel Electrophoresis (PFGE) is recognized as the "gold standard" for molecular subtyping, yet studies on clonal relationships in India are limited. PFGE was used to study the clonal relationships of 22 isolates of Burkholderia cenocepacia from 12 patients admitted to a critical care unit during 2 months (November and December 2021). PFGE revealed three different profiles with 15 isolates belonging to a single cluster suggesting a common source within the hospital, emphasizing the need for preventive measures to control B. cenocepacia transmission., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

Purpose: Burkholderia cepacia complex (Bcc) is a diverse group of environmental bacteria associated with opportunistic infections. The identification of Bcc using conventional methods poses challenges. Bcc infections are difficult to treat due to intrinsic antibiotic resistance. The study aimed to investigate the species distribution and antimicrobial susceptibility of clinical Bcc isolates., Methods: A total of 153 Bcc isolates obtained from clinical samples were analysed. Species identification was carried out using automated methods, including MALDI-TOF MS and VITEK2. Antimicrobial susceptibility testing was performed using the disc diffusion method., Results: Burkholderia cenocepacia (70.5%) emerged as the most prevalent species, followed by Burkholderia contaminans (9.8%) and Burkholderia cepacia (7.2%). Ventilator-associated pneumonia (38.6%) was the most common infection, followed by sepsis (28.1%). Co-existence of Bcc with other pathogens in many cases suggested potential co-infection scenarios. Antimicrobial susceptibility revealed that ceftazidime, co-trimoxazole and meropenem were the most effective drugs, while levofloxacin proved to be the least effective. Moderate susceptibility was noted to minocycline, with 4.6% of isolates exhibiting multi-drug resistance., Conclusion: This study provides valuable insights into the prevalence, clinical associations, and antibiotic susceptibility of Bcc in India. It highlights the importance of Bcc as a nosocomial pathogen, especially in vulnerable patient populations. The findings contribute to understanding Bcc infections, their distribution, and emphasize the necessity for accurate identification methods in clinical settings., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Nil reports was provided by nil. Nil reports a relationship with nil that includes:. Nil has patent pending to nil. nil If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Indian Association of Medical Microbiologists. Published by Elsevier B.V. All rights reserved.)

The present study investigated the effects of land use/land cover (LU/LC) changes on atmospheric carbon dioxide (CO 2 ) and methane (CH 4 ) concentrations over the sub-urban region of India (Shadnagar) using continuous decadal CO 2 and CH 4 in-situ data measured by the greenhouse gas analyser (GGA). Data was collected from 2013 to 2022 at a 1 Hz frequency. Analysis of the current study indicates that during pre-monsoon, the seasonal maximum of CO 2 was 409.91 ± 9.26 ppm (μ ± 1σ), while the minimum during monsoon was about 401.64 ± 7.13 ppm. Post-monsoon has a high seasonal mean CH 4 concentration of 2.08 ± 0.06 ppm, while monsoon has a low seasonal mean CH 4 concentration of 1.88 ± 0.03 ppm. The primary classes, such as forest, crop, and built-up, were considered to estimate the effect of LU/LC changes on atmospheric CO 2 and CH 4 concentrations. Between 2005 and 2021, the study's results show that the built-up area at radii of 10 km, 20 km, and 50 km increased by 0.17 %, 0.10 %, and 0.4 %, respectively. While other LU/LC categories declined by 30 %, agriculture areas increased by 30 % on average. As a result, the CO 2 and CH 4 concentrations at the study site are increased by 6 % (26 ppm) and 6.5 % (140 ppb), respectively. The present study utilised the fire-based carbon emissions data from the Global Fire Emissions Database (GFED) to understand the impact on atmospheric CO 2 and CH 4 . Analysis of the present work investigated the influence of transported airmass on CO 2 and CH 4 during the pre-monsoon and post-monsoon seasons using the HYSPLIT trajectories and found emissions were from the northwest, southeast, and northeast of the study site. Further, in-situ CO 2 and CH 4 records are compared against the MIROC4-ACTM simulation, and strong agreement was found with bias of 1.80 ppm and 0.98 ppb for CO 2 and CH 4 , respectively., Competing Interests: Declaration of competing interest The authors declare they have no conflict of Interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In this study, a highly fluorescent and receptor-free phenothiazine derivative (PDAB) was developed to detect picric acid. A combination of steady-state and time-resolved fluorescence studies was conducted to examine the excited state behavior of PDAB with picric acid in solution. The PDAB probe displayed a significant degree of selectivity and was highly sensitive to picric acid, with an extremely low detection limit of 9.82 nM. Time-resolved fluorescence quenching studies exhibit direct evidence of an inner filter effect-based sensing mechanism. Using the Parker equation, a thorough analysis was done to correct the inner filter effect on the sensing of picric acid. Overall, these studies provide critical information on the sensing mechanism for picric acid detection., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Bioelectrical impedance analysis (BIA) is a minimally invasive, safe, easy, and quick technology used to determine body composition., Objectives: We compared the relationship among impedance indices obtained using single-frequency BIA, multi-frequency BIA, bioelectrical impedance spectroscopy (BIS), and skeletal muscle mass (SMM) of physically active young men and athletes using the creatine (methyl-d 3 ) dilution method. We also compared the SMM and intracellular water (ICW) of athletes and active young men measured using a reference stable isotope dilution and BIS method, respectively., Methods: We analyzed data from 28 men (mean age, 20 ± 2 y) who exercised regularly. Single-frequency BIA at 5 kHz and 50 kHz (R 5 and R 50 ), multi-frequency BIA (R 250-5 ), and BIS (R ICW ) methods of determining the SMM were compared. The deuterium and sodium bromide dilution methods of obtaining the total body water, ICW, and extracellular water measurements were also used, and the results were compared to those acquired using bioimpedance methods., Results: The correlation coefficients between SMM and L 2 /R 5 , L 2 /R 50 , L 2 /R 250-5 , and L 2 /R ICW were 0.738, 0.762, 0.790, and 0.790, respectively (P < 0.01). The correlation coefficients between ICW and L 2 /R 5 , L 2 /R 50 , L 2 /R 250-5 , and L 2 /R ICW were 0.660, 0.687, 0.758, and 0.730, respectively (P < 0.001). However, the correlation coefficients of L 2 /R 50 , L 2 /R 250-5 , and L 2 /R ICW for SMM and ICW were not significantly different., Conclusions: Our findings suggest that single-frequency BIA at L 2 /R 50 , multi-frequency BIA, and BIS are valid for assessing the SMM of athletes and active young men. Additionally, we confirmed that the SMM and ICW were correlated with single-frequency BIA, multi-frequency BIA, and BIS. Bioimpedance technologies may be dependable and practical means for assessing SMM and hydration compartment status of active young adult males; however, cross-validation is needed., (Copyright © 2023 American Society for Nutrition. Published by Elsevier Inc. All rights reserved.)

Background: AICA (5-aminoimidazole-4-carboxamide) ribosiduria is an inborn error in purine biosynthesis caused due to biallelic pathogenic variants in the 5-aminoimidazole-4-carboxamide ribonucleotide-formyltransferase/imp cyclohydrolase (ATIC) gene located on chromosome 2q35. ATIC codes for a bifunctional enzyme, AICAR transformylase and inosine monophosphate (IMP) cyclohydrolase, which catalyse the last two steps of de novo purine synthesis. This disorder has been previously reported in only 4 cases worldwide, and herein, we report the first from India., Case Report: The proband presented with global developmental delay, developmental hip dysplasia (DDH), acyanotic heart disease and nystagmoid eye movements. Whole exome sequencing (WES) identified compound heterozygous pathogenic variants in the ATIC. A novel splice site variant; c.1321-2A > G and a previously reported missense variant; c.1277A > G (p.Lys426Arg) were identified. Segregation analysis of parents showed the father to be a heterozygous carrier for the splice site variant and the mother, a heterozygous carrier for the missense variant., Conclusion: This case of a rare genetic disorder of purine biosynthesis of ATIC deficiency is the first case reported from India. Early diagnosis lead to early interventional therapy and genetic counselling., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.)

Many controllers are available in the market for controlling the Permanent Magnet Synchronous Motor (PMSM) drive application, though the most preferably used one is Proportional Integral (PI), controller. However, it is found that the PI and other latest controllers have their own merits and demerits while analyzing their outputs via comparison. Thus it is decided to test the deed of hybrid controllers that can serve a lot better than standalone controllers for precise control applications. In this article, a conventional PI controller has been applied in closed-loop system in combination with recent controllers like Proportional Resonant Controller (PRC), Fractional order Proportional Integral Derivative (FOPID), Hysteresis Current Controller (HCC) and Fuzzy Logic Controller (FLC). The resultant hybrid controllers were (i) PI-FOPID (ii) PI-FLC (iii) FOPID-FLC (iv) HCC-FLC and (v) PRC-FLC. All these hybrid controllers are designed using MATLAB platform and the speed and torque responses are compared to allocate the better performance award to the hybrid controllers. The continuous and intermittent loads are considered while registering time-domain response of PMSM-Pump application. With the aid of time-domain response and THD, the topology to be tested in prototype is chosen and tested for resemblance of the speed response with the simulation output. PI-FLC hybrid controller tends to render optimum performance characteristics among all the other hybrid controllers and the same is validated in real time through hardware results., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 ISA. Published by Elsevier Ltd. All rights reserved.)

Induced pluripotent stem cells (iPSCs) are a promising cell source for regenerative medicine. However, their feeder-free maintenance in undifferentiated states remains challenging. In recent past extensive studies have been directed using pristine or functionalized carbon nanotube in tissue engineering. Here we proposed thin films of functionalized carbon nanotubes (OH-single-walled CNTs [SWCNTs] and OH-multiwalled CNTs [MWCNTs]), as alternatives for the feeder-free in vitro culture of canine iPSCs (ciPSCs), considered as the cellular model. The ciPSC colonies could maintain their dome-shaped compactness and other characteristics when propagated on CNT films. Concomitantly, high cell viability and upregulation of pluripotency-associated genes and cell adhesion molecules were observed, further supported by molecular docking. Moreover, CNTs did not have profound toxic effects compared to feeder cultures as evident by cytocompatibility studies. Further, cardiac and neuronal differentiation of ciPSCs was induced on these films to determine their influence on the differentiation process. The cells retained differentiation potential and the nanotopographical features of the substrates provided positive cues to enhance differentiation to both lineages as evident by immunocytochemical staining and marker gene expression. Overall, OH-SWCNT provided better cues, maintained pluripotency, and induced the differentiation of ciPSCs. These results indicate that OH-functionalized CNT films could be used as alternatives for the feeder-free maintenance of ciPSCs towards prospective utilization in regenerative medicine., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Uranium (U) in groundwater is hazardous to human health, especially if it is present in drinking water. The semiarid regions of southern India chiefly depend on groundwater for drinking purposes. In this regard, a comprehensive sampling strategy was adopted to collect groundwater representing different lithologies of the region. The samples were collected in two different seasons and analysed for major and minor ions along with total U in the groundwater. Two samples during pre monsoon (PRM) and seven samples during post monsoon (POM) had U > 30 μgL -1 , which is above the World Health Organization's provisional guideline value. The high concentration of U (188 μgL -1 ) was observed in the alluvial formation though a few samples showed the release of U near the pink granite (39 μgL -1 ) and the concentration was low in the lateritic formation (10 μgL -1 ). The uranyl carbonato complexes UO 2 (CO 3 ) 2 2- and UO 2 (CO 3 ) 3 4- were associated with high pH which facilitated the transport of U into groundwater especially during POM. U 3 O 8 is the major form observed in groundwater compared to either UO 2 or UO 3 in the both seasons. The uranium oxides were observed to be more prevalent at the neutral pH. Though U concentration increases with pH, it is mainly governed by the redox conditions. The principal component analysis (PCA) analysis also suggested redox conditions in groundwater to be the major process facilitating the U release mechanism regardless of the season. The POM season has an additional source of U in groundwater due to the application of nitrogenous fertilizers in the alluvium region. Furthermore, redox mobilization factor was predominantly observed near the coastal region and in the agricultural regions. The process of infiltration of the fertilizer-induced U was enhanced by the agricultural runoff into the surface water bodies in the region. Health risk assessment was also carried out by determining annual effective dose rate, cancer mortality risk, lifetime average daily dose and hazard quotient to assess the portability of groundwater in the study area. Artificial recharge technique and reducing the usage of chemical based fertilizers for irrigation are suggested as sustainable plans to safeguard the vulnerable water resource in this region., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Infections on the wound surface are the major problem in restricting the healing process. To reduce the transmission and treat the infection, we have developed 0.05% and 0.1% octenidine dihydrochloride (Ocd) incorporated chitosan (Cs) based flexible bandages. Ocd is extensively used skin antiseptic for its mode of action over a broad spectrum of antimicrobial activity. The prepared antiseptic Cs-Ocd bandage was characterized using Fourier transform infrared spectroscopy (FT-IR) and scanning electron microscope (SEM). In addition, swelling, degradation, cytocompability, antibacterial, and anti-biofilm property of the developed bandages were studied. This highly porous nature of Cs-Ocd bandage showed enhanced swelling property, slow degradation profile and controlled release of Ocd. The prepared antiseptic bandage exhibited synergistic effect showing good hemostatic potential with Cs, excellent antimicrobial and anti-biofilm activity with Ocd against Staphylococcus aureus (S. aureus) and Candida auris (C. auris). Thus, the developed Cs-Ocd bandage can be used as potential antiseptic bandage for skin infections., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Hydrogels are excellent wound healing materials. However, due to the wear and tear at the wound site, hydrogels can lose their structural and functional integrity. To overcome this and to effectively seal the wound and control infection, an in-situ silver nanoparticles (AgNps) incorporated N, O-carboxymethyl chitosan (N, O-CMC) based self-healing hydrogel using ethylenediaminetetraacetic acid-ferric ion (EDTA: Fe 3+ ) complex was developed. The prepared N, O-CMC/AgNps hydrogel was characterized using FTIR, SEM, and TEM. The developed N, O-CMC/AgNps hydrogel was found to be adhesive, injectable, conductive, bio-compatible, and showed antibacterial activity against ATCC and clinical strains of E. coli, K. pneumonia, P. aeruginosa, S. aureus and MRSA. N, O-CMC/AgNps hydrogel also showed anti-biofilm activity against S. aureus, E. coli, and P. aeruginosa (ATCC strains). This developed antibacterial and self-healing N, O-CMC/AgNps hydrogel can be used in the treatment of infected wounds., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Effects of high protein (HP) diets and prolonged energy restriction (ER) on integrated muscle protein kinetics have not been determined., Objective: The objective of this study was to measure protein kinetics in response to prolonged ER and HP on muscle protein synthesis (MPS; absolute rates of synthesis) and muscle protein breakdown (MPB; half-lives) for proteins across the muscle proteome., Methods: Female 6-wk-old obese Zucker rats (Leprfa+/fa+, n = 48) were randomly assigned to one of four diets for 10 wk: ad libitum-standard protein (AL-SP; 15% kcal from protein), AL-HP (35% kcal from protein), ER-SP, and ER-HP (both fed 60% feed consumed by AL-SP). During week 10, heavy/deuterated water (2H2O) was administered by intraperitoneal injection, and isotopic steady-state was maintained via 2H2O in drinking water. Rats were euthanized after 1 wk, and mixed-MPS as well as fractional replacement rate (FRR), relative concentrations, and half-lives of individual muscle proteins were quantified in the gastrocnemius. Data were analyzed using 2-factor (energy × protein) ANOVAs and 2-tailed t-tests or binomial tests as appropriate., Results: Absolute MPS was lower in ER than AL for mixed-MPS (-29.6%; P < 0.001) and MPS of most proteins measured [23/26 myofibrillar, 48/60 cytoplasmic, and 46/60 mitochondrial (P < 0.05)], corresponding with lower gastrocnemius mass in ER compared with AL (-29.4%; P < 0.001). Although mixed-muscle protein half-life was not different between groups, prolonged half-lives were observed for most individual proteins in HP compared with SP in ER and AL (P < 0.001), corresponding with greater gastrocnemius mass in HP than SP (+5.3%; P = 0.043)., Conclusions: ER decreased absolute bulk MPS and most individual MPS rates compared with AL, and HP prolonged half-lives of most proteins across the proteome. These data suggest that HP, independent of energy intake, may reduce MPB, and reductions in MPS may contribute to lower gastrocnemius mass during ER by reducing protein deposition in obese female Zucker rats., (Published by Oxford University Press on behalf of the American Society for Nutrition 2021.)

7-ketocholesterol, a toxic oxidative product of oxysterol is a causative agent of several diseases and disabilities concomitant to aging including cardiovascular diseases like atherosclerosis. Auto-oxidation of cholesterol esters present in low-density lipoprotein (LDL) deposits lead to the formation of oxidized LDL (Ox-LDL) along with its byproducts, namely 7KCh. It is predominantly found in atherosclerotic plaque and also found to be more atherogenic than cholesterol by being cytotoxic, interfering with cellular homeostasis. This makes it a serious threat by being the foremost cause of morbidity and mortality worldwide and is likely to become more serious during forth coming years. It involves in mediating inflammatory mechanisms characterized by the advancement of fibroatheroma plaques. The atherosclerotic lesion is composed of Ox-LDL along with fibrotic mass consisting of immune cells and molecules. Macrophages being the specialized phagocytic cells, contribute to removal of detrimental contents of the lesion along with accumulated lipids leading to alteration of its biology and functionality due to its plasticity. Here, we have explored the known as well as proposed mechanisms involved with 7KCh associated atherogenesis along with potential therapeutic strategies for targeting 7KCh as a diagnostic and target in medicine., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Introduction: Dual antiplatelet therapy (DAPT) remains the cornerstone of acute coronary syndrome (ACS) management, and ticagrelor is one of the commonly used second antiplatelet agents. There is some evidence to suggest that morphine may reduce the antiplatelet effect of ticagrelor., Methods and Results: In a single-center, randomized controlled trial, we compared the effect of morphine and fentanyl on platelet aggregation (PA) among patients with ACS treated with ticagrelor. Platelet aggregation was studied by automated light transmittance aggregometry (LTA) at baseline, and at 2 h after ticagrelor loading. The primary outcome was the difference in the maximal inhibition of platelet aggregation [IPA(%)] between the groups at 2 h. Pain relief, and drug-related adverse events were secondary outcomes. Of 136 patients randomized, 70 received fentanyl and 66 received morphine. At baseline, the median (IQR) platelet aggregation [61.35% (54.6 to 70) Vs. 58.8% (52.7 to 72.9)] were comparable between the groups. There was no statistically significant difference between the fentanyl and the morphine groups in IPA at 2-h [85.88%(64.65-98.16) and 81.93%(44.2-98.03), p = 0.09]. However, morphine use was independently associated with a PA of >30% at 2 h (p < 0.009). There was no difference in adverse events., Conclusion: In patients with ACS, there was no significant difference between the use of fentanyl or morphine on the effect of ticagrelor on PA. (CTRI/2018/04/013423)., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background and Objective: Metabolic disorders including diabetes are associated with immune cell dysfunction. However, the effect of normal glucose metabolism or impairment thereof on immune cell gene expression is not well known. Hence, in this cross-sectional pilot study, we sought to determine the differences in gene expression in the peripheral blood mono-nuclear cells (PBMCs) of normal glucose tolerant (NGT) and prediabetic (PD) Asian Indian men, at fasting and in response to 75 g oral glucose load., Methods: Illumina HT12 bead chip-based microarray was performed on PBMCs at fasting and 2-h post load conditions for NGT (N = 6) and PD (N = 9) subjects. Following normalization and due quality control of the raw data, differentially expressed genes (DEGs) under different conditions within and across the two groups were identified using GeneSpring GX V12.0 software. Paired and unpaired Student's t-tests were applied along with fold change cut-offs for appropriate comparisons. Validation of the microarray data was carried out through real-time qPCR analysis. Significantly regulated biological pathways were analyzed by employing DEGs and DAVID resource. Deconvolution of the DEGs between NGT and PD subjects at fasting was performed using CIBERSORT and genes involved in regulatory T-cell (Treg) function were further analyzed for biological significance., Results: Glucose load specifically altered the expression of 112 genes in NGT and 356 genes in PD subjects. Biological significance analysis revealed transient up-regulation of innate and adaptive immune response related genes following oral glucose load in NGT individuals, which was not observed in PD subjects. Instead, in the PD group, glucose load led to an increase in the expression of pro-atherogenic and anti-angiogenic genes. Comparison of gene expression at fasting state in PD versus NGT revealed 21,707 differentially expressed genes. Biological significance analysis of the immune function related genes between these two groups (at fasting) revealed higher gene expression of members of the TLR signaling, MHC class II molecules, and T-cell receptor, chemotaxis and adhesion pathways in PD subjects. Expression of interferon-γ (IFN-γ) and TNFα was higher and that of type-1 interferons and TGF-β was lower at fasting state in PD subjects compared to NGT. Additionally, expression of multiple proteasome subunits and protein arginine methyl transferase genes (PRMTs) were higher and that of Treg specific genes was significantly distinct at fasting in PD subjects compared to NGT., Conclusion: Prediabetes uncovers constitutive TLR activation, enhanced IFN-γ signaling, and Treg dysfunction at fasting along with altered gene expression response to oral glucose load., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)

Introduction: There has been considerable concern in the UK with what seems to have been an increase in so-called 'Acid Attacks'. The key data sources (Police data, Hospital admissions and Burns unit data) have limitations in capturing the acid attacks comprehensively. Incidents not reported to the police are missed in the Police data. The more serious injuries are included in the hospital admissions data, with no information on people with less severe injuries, not accessing health care. Burns unit data reveals detailed information on the burns treatment but represents only a small percent of all the acid attacks. Our aim was to explore the role of media reports as an additional data source., Methods: Data was obtained from the public domain using generic online search engines along with a formal medical literature review. Search parameters included any news articles on 'Acid Attacks' printed between 01/01/2016 and 31/12/2017 in England and Articles in National Press only. We compared the data from media reports to the only other data sources available on these crimes which were (a) Crime statistics from police (b) the proportion treated in hospital (c) the subgroup treated in the burns service in the highest incidence location in the UK., Results: Two hundred and Thirty media articles in total were found in the preliminary search. Following the application of the exclusion criteria, sixty attacks were analysed. The demographic data, the geographic data were obtained from the articles and the results were analysed using Microsoft Excel. There were a total of 118 survivors with an average age of 29.5 years and a male to female ratio of 5.1:1. There were no reported deaths. In the assailants group, the average age was 21.6 years with a male to female ratio of 15.7:1. All the data sources revealed higher male survivor predominance. The average age of the survivors was similar in the media reports, police data and the Burns centre data and was higher in the hospital data. Information on assailants and motives, available only on media reports and police data, corroborated well with each other. Media reports gave further information on the circumstances of the incident, the location and the number of survivors per assault, which was not available on any other data source. Though there was a rise in chemical assaults reported in media reports and MPS data in 2017 compared to the previous year, there was no rise in chemical assault related hospital admissions., Conclusion: The majority of the survivors were males, which is consistent between all UK data sources. Media reports revealed that the South east of England had the majority of chemical assaults in England. Data from this source provides a further piece in the jigsaw especially in relation to the circumstances, the geographic location of the chemical assault and number of survivors per incident. We acknowledge the limitations of media reporting. In the absence of a formal database for such injuries and incomplete data from various sources, we have to consider all possible data sources to provide new information. We have discussed the utility, pros & cons of media reports as one of the additional sources of information to better understand these injuries., (Copyright © 2019 Elsevier Ltd and ISBI. All rights reserved.)

Chronic pain and depression are often comorbid exhibiting common clinical presentations and biological connections related to central nervous system sensitization. Epigenetic regulation of gene expression in the brain plays a crucial role in response to long-lasting stress and chronic pain, and microRNA imbalance in the prefrontal cortex (PFC) might be involved in central sensitization. Male Sprague Dawley rats were subjected to unpredictable chronic mild stress (UCMS) and spared nerve injury (SNI) to initiate depressive-like behavior and chronic pain behavior, respectively. The next-generation sequencing technique was employed to analyze PFC microRNAs in both the UCMS and SNI models. Rats exposed to either UCMS or SNI exhibited both depressive-like and chronic pain behaviors. Five specific microRNAs (miR-10a-5p, miR-182, miR-200a-3p, miR-200b-3p, and miR-429) were simultaneously down-regulated in the depressive-like and chronic pain models after 4 weeks of short-term stress. Gene ontology revealed that the 4-week period of stress enhanced neurogenesis. Only the miR-200a-3p level was continuously elevated under prolonged stress, suggesting roles of reduced neurogenesis, inflammatory activation, disturbed circadian rhythm, lipid metabolism, and insulin secretion in the co-existence of pain and depression. Thus we conclude that miR-200a-3p might be a specific biomarker of central sensitization in chronic pain and depression., (Copyright © 2019 Elsevier Inc. All rights reserved.)

In recent, targeting mitochondria in cancer is considered to be a challenging task. This report illustrates preliminary findings from an investigation of the conjugation of gold nanoparticles with a bioactive natural compound, phloroglucinol targeting mitochondrial transmembrane potential of HeLa cancer cells. We systematically investigated the formation of gold-nano conjugates over precisely controlled reaction conditions. Their sharp features enable superior surface plasmon resonance, morphology, surface charge, and stability. We show that gold-nano conjugates scavenging free radicals and persuade cell death in HeLa cancer cells. We also show that gold-nano conjugates induce apoptosis by promoting mitochondrial transmembrane permeation via fluorescent microscopic studies. This work gives new insights into bridging metabolomics and nanotechnology into developing novel lead therapeutic molecules., (Copyright © 2019. Published by Elsevier B.V.)

CCAAT/enhancer binding protein ε (CEBPE) is an essential transcription factor for granulocytic differentiation. Mutations of CEBPE occur in individuals with neutrophil-specific granule deficiency (SGD), which is characterized by defects in neutrophil maturation. Cebpe -knockout mice also exhibit defects in terminal differentiation of granulocytes, a phenotype reminiscent of SGD. Analysis of DNase I hypersensitive sites sequencing data revealed an open chromatin region 6 kb downstream of the transcriptional start site of Cebpe in murine myeloid cells. We identified an interaction between this +6-kb region and the core promoter of Cebpe using circular chromosome conformation capture sequencing (4C-seq). To understand the role of this putative enhancer in transcriptional regulation of Cebpe , we targeted it using catalytically inactive Cas9 fused to Krüppel-associated box (KRAB) domain and observed a significant downregulation of transcript and protein levels of CEBPE in cells expressing guide RNA targeting the +6-kb region. To further investigate the role of this novel enhancer further in myelopoiesis, we generated mice with deletion of this region using CRISPR/Cas9 technology. Germline deletion of the +6-kb enhancer resulted in reduced levels of CEBPE and its target genes and caused a severe block in granulocytic differentiation. We also identified binding of CEBPA and CEBPE to the +6-kb enhancer, which suggests their role in regulating the expression of Cebpe In summary, we have identified a novel enhancer crucial for regulating expression of Cebpe and required for normal granulocytic differentiation., (© 2019 by The American Society of Hematology.)

Aim: To assess the efficacy of the lotus petal flap in difficult pilonidal sinus management., Background: Pilonidal sinuses may be difficult to treat. Five year recurrence rates range from 18% to 50% Recurrence rates fall with primary closure rather than healing by secondary intention. Techniques such as z-plasty however, distort natal architecture. The lotus petal flap taken from the superior buttock fills dead space whilst conforming to the natural concave appearance of the natal cleft. The contralateral buttock is spared. It is straightforward and reproducible. Multiple perforators make it robust and promote wound healing in this difficult group., Method: We present a series of 14 patients who had a lotus petal flap reconstruction following pilonidal sinus excision between 2007 and 2015. The majority of these patients had previous multiple failed attempts at eradication. Recurrence rates, re-operation rates, time for complete healing, wound breakdown, discharge, infection, cosmesis and patient comfort were assessed., Results: Many patients had coarse hair; felt to predispose to recurrence of symptoms, poor hygiene and prolonged wound healing. 50% of patients underwent Alexandrite laser (755 nm wavelength) for a minimum of 6 treatments. There was excellent compliance and good patient outcome. Overall in this complex patient group only 14% had prolonged wound healing and recurrence rates were lower than those in the literature., Conclusion: The lotus petal flap is an excellent choice for problematic pilonidal sinus reconstruction. When combined with tumour like excision, meticulous surgical technique and complimentary laser hair removal results can be improved further., (Crown Copyright © 2018. Published by Elsevier Ltd. All rights reserved.)

Purpose: Different amounts of opioid are required for the relief of cancer pain in different individuals, raising the possibility that genetic factors play a role. We tested the hypothesis that genetic variations in the TAOK3 (TAO kinase 3, encoding serine/threonine-protein kinase) explain some of the interindividual variations related to the morphine-equivalent daily dose (MEDD) in patients with cancer., Experimental Design: We selected two single-nucleotide polymorphisms (SNPs) in the TAOK3, reported earlier to associate with higher MEDD in postoperative pain based on genome-wide association study. We investigated their association with MEDD in Canadian patients with cancer (n = 110) admitted to a tertiary palliative care unit. SNPs analyzed were rs1277441 (C/T, C = minor allele) and rs795484 (A/G, A = minor allele)., Results: Minor allele frequencies in our population were 0.29 (rs1277441) and 0.28 (rs795484). These SNPs were in perfect linkage disequilibrium (r 2  = 0.97). SNPs in TAOK3 showed a significant association with mean MEDD ≥800 mg. For rs795484, MEDD values ≥800 mg occurred in patients who were GG (7%), GA (18%), and AA (57%) (P = 0.004; Fisher's exact test); similar results were obtained for rs1277441. Homozygous variants for either SNP had received higher numbers of different opioids (P = 0.021)., Conclusion: In this cohort of patients with advanced cancer pain, TAOK3 SNPs were associated with opioid doses. This result supports the original findings from a GWAS in postoperative patients. The proportions of variant homozygotes (8.2% of patients) and their requirement for higher doses of opioids would appear potentially clinically important and should be validated in further studies., (Copyright © 2018 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Primary small cell ovarian cancer of pulmonary type (SCCOPT) is a rare aggressive ovarian tumour with an incidence of <1%, usually occurring in perimenopausal or postmenopausal women and known to have a poor prognosis. Current treatment is platinum based but has not resulted in long term survival., Case Presentation: We report a case of a 77-year old Caucasian woman who presented initially with a one-week history of abdominal discomfort with raised inflammatory markers and Ca125 of 50 μ/ml. Calcium levels were normal. She underwent primary debulking surgery, and histology showed a tumour comprising areas of classical small-cell carcinoma morphology. 6 cycles of adjuvant chemotherapy with carboplatin was offered. Relapsed/progressive disease was noted after 3 months of chemotherapy and patient died 7 months after treatment completion., Conclusions: SCCOPT is a rare aggressive malignancy with majority of the women having an overall survival of 2 years. There is no clear consensus for the diagnosis and optimal treatment.

The glial cell line-derived neurotrophic factor (GDNF) family of ligands (GFLs) comprising of GDNF, neurturin, artemin, and persephin plays an important role in the development and maintenance of the central and peripheral nervous system, renal morphogenesis, and spermatogenesis. Here we review our current understanding of GFL biology, and supported by recent progress in the area, we examine their emerging role in endocrine-related and other non-hormone-dependent solid neoplasms. The ability of GFLs to elicit actions that resemble those perturbed in an oncogenic phenotype, alongside mounting evidence of GFL involvement in tumor progression, presents novel opportunities for therapeutic intervention., (Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.)

The computational studies namely molecular docking simulations and Comparative Molecular Field Analysis (CoMFA) are executed on series of 52 novel aryl chalcones derivatives using Plasmodium falciparum cysteine proteases (falcipain - 2) as vital target. In the present study, the correlation between different molecular field effects namely steric and electrostatic interactions and chemical structures to the inhibitory activities of novel aryl chalcone derivatives is inferred to perceive the major structural prerequisites for the rational design and development of potent and novel lead anti-malarial compound. The apparent binding conformations of all the compounds at the active site of falcipain - 2 and the hydrogen-bond interactions which could be used to modify the inhibitory activities are identified by using Surflex-dock study. Statistically significant CoMFA model has been developed with the cross-validated correlation coefficient (q(2)) of 0.912 and the non-cross-validated correlation coefficient (r(2)) of 0.901. Standard error of estimation (SEE) of 0.210, with the optimum number of components is ten. The predictability of the derived model is examined with a test set consists of sixteen compounds and the predicted r(2) value is found to be 0.924. The docking and QSAR study results confer crucial suggestions for the optimization of novel 1,3-diphenyl-2-propen-1-one derivatives and synthesis of effective anti- malarial compounds., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Idiopathic pulmonary fibrosis (IPF) is characterized by excessive scarring of the lung parenchyma, resulting in a steady decline of lung function and ultimately respiratory failure. The disease course of IPF is extremely variable, with some patients exhibiting stability of symptoms for prolonged periods of time, whereas others exhibit rapid progression and loss of lung function. Viral infections have been implicated in IPF and linked to disease severity; however, whether they directly contribute to progression is unclear. We previously classified patients as rapid and slow progressors on the basis of clinical features and expression of the pathogen recognition receptor, Toll-like receptor 9 (TLR9). Activation of TLR9 in vivo exacerbated IPF in mice and induced differentiation of myofibroblasts in vitro, but the mechanism of TLR9 up-regulation and progression of fibrosis are unknown. Herein, we investigate whether transforming growth factor (TGF)-β, a pleiotropic cytokine central to IPF pathogenesis, regulates TLR9 in lung myofibroblasts. Results showed induction of TLR9 expression by TGF-β in lung myofibroblasts and a distinct profibrotic myofibroblast phenotype driven by stimulation with the TLR9 agonist, CpG-DNA. Chronic TLR9 stimulation resulted in stably differentiated α-smooth muscle actin(+)/platelet-derived growth factor receptor α(+)/CD44(+)/matrix metalloproteinase-14(+)/matrix metalloproteinase-2(+) myofibroblasts, which secrete inflammatory cytokines, invade Matrigel toward platelet-derived growth factor, and resist hypoxia-induced apoptosis. These results suggest a mechanism by which TGF-β and TLR9 responses in myofibroblasts collaborate to drive rapid progression of IPF., (Copyright © 2015 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)

The family of lysosome-associated membrane proteins (LAMP) includes the ubiquitously expressed LAMP1 and LAMP2, which account for half of the proteins in the lysosomal membrane. Another member of the LAMP family is LAMP3, which is expressed only in certain cell types and differentiation stages. LAMP3 expression is linked with poor prognosis of certain cancers, and the locus where it is encoded was identified as a risk factor for Parkinson's disease (PD). Here, we investigated the role of LAMP3 in the two main cellular degradation pathways, the proteasome and autophagy. LAMP3 mRNA was not detected in mouse models of PD or in the brain of human patients. However, it was strongly induced upon proteasomal inhibition in the neuroblastoma cell line SH-SY5Y. Induction of LAMP3 mRNA following proteasomal inhibition was dependent on UPR transcription factor ATF4 signaling and induced autophagic flux. Prevention of LAMP3 induction enhanced apoptotic cell death. In summary, these data demonstrate that LAMP3 regulation as part of the UPR contributes to protein degradation and cell survival during proteasomal dysfunction. This link between autophagy and the proteasome may be of special importance for the treatment of tumor cells with proteasomal inhibitors., (Copyright © 2015 The Authors. Published by Elsevier GmbH.. All rights reserved.)

Background: Cardiovascular diseases (CVDs) are commonly comorbid with depression and vice versa. Polyunsaturated fatty acids (PUFAs) have been suggested to mediate in CVDs and depression in cross-sectional and observational studies. With the patients of CVDs, we investigated the role of depression on the effect of PUFAs., Methods: Forty-four patients with CVDs were recruited and assessed with Hamilton depression rating scale (HAMD). Patients' CVDs markers were measured by electrocardiogram and their red blood cell (RBC) samples were collected for PUFAs analyses., Results: The data of 44 subjects were analyzed; where 10 participants (23%) with CVDs had moderate or severe depression, defined by a HAMD score more than 19 points. The moderate depression group had lower docosahexaenoic acid (DHA), omega-3 (N3) and omega-6(N6) to N3 (N6/N3) ratio than non-depression group (HAMD score less than 8), while no differences between the 2 groups in terms of corrected QT (QTc) intervals and high sensitivity C-reactive protein (hsCRP) levels. Furthermore, when we analyzed the data with an inclusion of a more heterogeneous depression group, where HAMD score is greater than or equal to 10 (mild depression group, N=24), the differences in PUFAs levels between the 2 groups disappear. Secondary analysis of the moderate depression group showed a positive correlation between DHA, N3 PUFAs, and N6/N3 ratio and total HAMD scores, a positive correlation between N3 PUFAs and QTc intervals in non-depression group., Conclusion: Moderate depression group of patients with CVDs had lower levels of DHA, N3, and N6/N3 ratio than non-depression group, while both groups had no differences in QTc and hsCRP. On the other hand, the differences in PUFAs levels disappear in the mild depression group after inclusion of patients with CVDs with greater heterogeneity of depression. Hence, the role of N3 PUFAs is implicated in depression of patients with CVDs if the depression status is more strictly defined., (Copyright © 2014 Elsevier Inc. All rights reserved.)

A series of biologically important substituted 3-fluorosalicylaldehyde derivatives (1a-h) with various primary amines were synthesized by using ionic liquid (1-Butyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide) as an efficient catalyst. A new series of Schiff base derivatives (1a-h) were synthesized and characterized by IR, NMR ((1)H, (13)C, (1)H-(1)H COSY and HSQC), mass spectra and elemental analysis. Further crystal structure of compound 1a was evaluated by single crystal X-ray diffraction techniques. All the synthesized compounds were screened for in vitro antimicrobial activity against a panel of selected bacterial and fungal strains using Streptomycin and Amphotericin B as standards. Most of the synthesized compounds demonstrated moderate effects on both antibacterial and antifungal activities at minimum inhibitory concentrations (MIC's)., (Copyright © 2013. Published by Elsevier B.V.)

Background: Fibrosis or inflammation of the bronchioles is a well-known manifestation of connective tissue disease (CTD). However, the natural history of CTD-related bronchiolitis is largely unknown., Methods: We analyzed consecutive patients evaluated at National Jewish Health (Denver, CO) from 1998 to 2008 with CTD and surgical lung biopsy-confirmed bronchiolitis. Linear mixed effects models were used to estimate the longitudinal postbronchodilator FEV1 %predicted (%pred) course and differences between subjects with or without constrictive bronchiolitis (CB)., Results: Of 28 subjects with a mean age of 53 ± 9 years, fourteen (50%) had CB. The most common CTD diagnosis was rheumatoid arthritis (n = 14; 50%). There were no significant differences in demographics, smoking status, underlying CTD diagnoses, 6-min walk distance, dyspnea score or drug therapy between subjects with CB and those with cellular bronchiolitis. Three subjects with CB (11%) and four with cellular bronchiolitis (14%) died. Compared with subjects with CB, those with cellular bronchiolitis had higher mean FEV1 %pred at all times. There were no significant differences in FEV1 %pred slope within- or between-groups (CB vs. cellular bronchiolitis) preceding surgical lung biopsy or afterward., Conclusion: Subjects with CTD-related CB had lower FEV1 %pred values than those with CTD-related cellular bronchiolitis at all time points, but FEV1 %pred remained stable over time in both groups regardless of therapy received., (Copyright © 2013 Elsevier Ltd. All rights reserved.)

We present a 55-year-old male who presented with painful non-healing ulcers on the lower lip and scrotum associated with productive cough, fever, anorexia and dysuria. Erythrocyte sedimentation rate was raised, sputum was positive for acid fast bacilli. Chest X-ray was suggestive of pulmonary tuberculosis. A prostate biopsy was also suggestive of tuberculosis. A diagnosis of disseminated tuberculosis was made and the patient showed a good response in two weeks.

Photocatalytic activity of TiO2 and zeolites supported TiO2 were investigated using propoxur as a model pollutant. Hbeta, HY and H-ZSM-5 zeolites were examined as supports for TiO2. Hbeta was chosen as the TiO2 support based on the adsorption capacity of propoxur on these zeolites (Hbeta>HY=H-ZSM-5). TiO2/Hbeta photocatalysts with different wt.% were prepared and characterized by XRD, FT-IR and BET surface area. The progress of photocatalytic degradation of aqueous propoxur solution using TiO2 (Degussa P-25) and TiO2 supported on Hbeta zeolite was monitored using TOC analyzer, HPLC and UV-vis spectrophotometer. The degradation of propoxur was systematically studied by varying the experimental parameters in order to achieve maximum degradation efficiency. The initial rate of degradation with TiO2/Hbeta was higher than with bare TiO2. TOC results revealed that TiO2 requires 600min for complete mineralization of propoxur whereas TiO2/Hbeta requires only 480min. TiO2/Hbeta showed enhanced photodegradation due to its high adsorption capacity on which the pollutant molecules are pooled closely and hence degraded effectively.

Mammalian spermiogenesis, a process where haploid male germ cells differentiate to become mature spermatozoa, entails dramatic morphological and biochemical changes including remodeling of the germ cell chromatin. Proteins that contain one or more plant homeodomain (PHD) fingers have been implicated in the regulation of chromatin structure and function. Pygopus 2 (Pygo2) belongs to a family of evolutionarily conserved PHD finger proteins thought to act as co-activators of Wnt signaling effector complexes composed of beta-catenin and LEF/TCF transcription factor. Here we analyze mice containing hypomorphic alleles of pygopus 2 (Pygo2 or mpygo2) and uncover a beta-catenin-independent involvement of the Pygo2 protein in spermiogenesis. Pygo2 is expressed in elongating spermatids at stages when chromatin remodeling occurs, and block of Pygo2 function leads to spermiogenesis arrest and consequent infertility. Analysis of spermiogenesis in Pygo2 mutants reveals reduced expression of select post-meiotic genes including protamines, transition protein 2, and H1fnt, all of which are required for germ cell chromatin condensation, and drastically altered pattern of histone H3 hyperacetylation. These findings suggest that Pygo2 is involved in the chromatin remodeling events that lead to nuclear compaction of male germ cells.

The photocatalytic degradation of carbofuran (2,3-dihydro-2,2-dimethylbenzofuran-7-yl methylcarbamate) was investigated in an aqueous solution using Degussa P-25 TiO2 and ZnO as photocatalysts. The progress of degradation was monitored using TOC analyzer, HPLC, GC-MS and UV-vis spectrophotometer. The effects of various experimental parameters such as initial concentration of carbofuran, pH of the solution, catalyst loading and light intensity were systematically studied in order to achieve maximum degradation efficiency. The complete mineralization of carbofuran was confirmed by TOC analyzer. The degradation with ZnO showed less efficiency than TiO2. The formation of NO(3)(-) was identified and quantified using HPLC. In addition, four different intermediates formed during the degradation process were also identified and characterized by GC-MS. The mineralization rate was compared with lamps of wavelength 254 and 365 nm under similar conditions. The rate with 254 nm was observed to be very close to that of 365 nm.