Genomic surveillance of SARS-CoV-2 and emergence of XBB.1.16 variant in Rajasthan.

PURPOSE: Genomic surveillance of positive SARS-CoV-2 samples is important to monitor the genetic changes occurring in virus, this was enhanced after the WHO designation of XBB.1.16 as a variant under monitoring in March 2023. From 5th February till May 6, 2023 all positive SARS-CoV-2 samples were monitored for genetic changes. METHODS: A total of 1757 samples having Ct value <25 (for E and ORF gene) from different districts of Rajasthan were processed for Next Generation Sequencing (NGS). The FASTA files obtained on sequencing were used for lineage determination using Nextclade and phylogenetic tree construction. RESULTS AND CONCLUSIONS: Sequencing and lineage identification was done in 1624 samples. XBB.1.16 was the predominant lineage in 1413 (87.0%) cases while rest was other XBB (207, 12.74%) and other lineages (4, 0.2%). Of the 1413 XBB.1.16 cases, 57.47% were males and 42.53% were females. Majority (66.53%) belonged to 19-59 year age. 84.15% of XBB.1.16 cases were infected for the first time. Hospitalization was required in only 2.2% cases and death was reported in 5 (0.35%) patients. Most of the cases were symptomatic and the commonest symptoms were fever, cough and rhinorrhea. Co-morbidities were present in 414 (29.3%) cases. Enhanced genomic surveillance helped to rapidly identify the spread of XBB variant in Rajasthan. This in turn helped to take control measures to prevent spread of virus and estimate public health risks of the new variant relative to the previously circulating lineages. XBB variant was found to spread rapidly but produced milder disease.

Application of LAMP assay for detection of carbapenem-resistant Acinetobacter calcoaceticus-Acinetobacter baumannii complex in ICU admitted sepsis patients: A rapid and cost-effective diagnostic tool.

Carbapenem-resistant significant members of Acinetobacter calcoaceticus-Acinetobacter baumannii (CR-SM-ACB) complex have emerged as an important cause of sepsis, especially in ICUs. This study demonstrates the application of loop-mediated-isothermal-amplification (LAMP) assay for detection of CR-SM-ACB-complex from patients with sepsis. Whole-blood and culture-broths(CB) collected from patients with culture-positive sepsis were subjected to LAMP and compared with PCR, and RealAmp. Vitek-2 system and conventional PCR results were used as confirmatory references. The sensitivity and specificity of LAMP(97 % & 100 %) and RealAmp(100 % & 100 %) for detection of CR-SM-ACB-complex from CB were better than PCR(87 % & 100 %). Diagnostic accuracy of LAMP, RealAmp, and PCR for detection of SM-ACB-complex from CB was 98.5 %, 100 %, and 88.5 % respectively. Turnaround time of Culture, LAMP, PCR, and RealAmp was 28-53, 6-20, 9-23, and 6-20hours, respectively. LAMP is a simple, inexpensive tool that can be applied directly to positive CB and may be customized to detect emerging pathogens and locally-prevalent resistance genes and to optimize antimicrobial use.

Exploring the evolutionary and pathogenic role of Acinetobacter baumannii biofilm-associated protein (Bap) through in silico structural modeling.

Acinetobacter species encode for extracellularly secreted Biofilm-associated protein (Bap), a multi-domain protein with variable molecular weights reaching several hundred kilodaltons. Bap is crucial for the development of multi-dimensional structures of mature biofilms. In our investigation, we analyzed 7338 sequences of A. baumannii from the NCBI database and found that Bap or Bap-like protein (BLP) was present in 6422 (87.52%) isolates. Further classification revealed that 12.12% carried Type-1 Bap, 68.44% had Type-2, 6.91% had Type-3, 0.05% had Type-6 or SDF-Type, and 12.51% lacked Bap or BLP. The majority of isolates with Type-1, Type-2, and Type-3 Bap belonged to ST1, ST2, and ST25, respectively. Phylogenetic analysis suggested that Type-1 Bap is the most ancient, while Type-3 and SDF-Type have evolved recently. Studying the interaction of predicted Bap structures with human CEACAM-1 and PIgR showed that Bap with its BIg13 and BIg6 domains interact with the N-terminal domain of CEACAM-1, involving Arg43 and Glu40, involved in CEACAM-1 dimerization. Also, we found that recently evolved Type-3 and SDF-Type Bap showed greater interaction with CEACAM-1 and PIgR. It can be asserted that the evolution of Bap has conferred enhanced virulence characteristics to A. baumannii with increased interaction with CEACAM-1 and PIgR. Using in silico approaches, this study explores the evolutionary, physicochemical, and structural features of A. baumannii Bap and unravels its crucial role in mediating interaction with human CEACAM-1 and PIgR through detailed structure modelling. These findings advance our understanding of A. baumannii Bap and highlight its role in pathogenesis.

Antimony susceptible Leishmania donovani: evidence from in vitro drug susceptibility of parasites isolated from patients of post-kala-azar dermal leishmaniasis in pre- and post-miltefosine era.

Post-kala-azar dermal leishmaniasis (PKDL) patients are a key source of Leishmania donovani parasites, hindering the goal of eliminating visceral leishmaniasis (VL). Monitoring treatment response and parasite susceptibility is essential due to increasing drug resistance. We assessed the drug susceptibility of PKDL isolates (n = 18) from pre-miltefosine (MIL) era (1997-2004) with isolates (n = 16) from the post-miltefosine era (2010-2019) and post-miltefosine treatment relapse isolates (n = 5) towards miltefosine and amphotericin B (AmB) at promastigote stage and towards sodium antimony gluconate (SAG) at amastigote stage. PKDL isolates were examined for mutation in gene-encoding AQP1 transporter, C26882T mutation on chromosome 24, and miltefosine-transporter (MT). PKDL isolates from the post-miltefosine era were significantly more susceptible to SAG than SAG-resistant isolates from the pre-miltefosine era (P = 0.0002). There was no significant difference in the susceptibility of parasites to miltefosine between pre- and post-miltefosine era isolates. The susceptibility of PKDL isolates towards AmB remained unchanged between the pre- and post-miltefosine era. However, the post-miltefosine era isolates had a higher IC50 value towards AmB compared with PKDL relapse isolates. We did not find any association between AQP1 gene sequence variation and susceptibility to SAG, or between miltefosine susceptibility and single nucleotide polymorphisms (SNPs in the MT gene. This study demonstrates that recent isolates of Leishmania have resumed susceptibility to antimonials in vitro. The study also offers significant insights into the intrinsic drug susceptibility of Leishmania parasites over the past two decades, covering the period before the introduction of miltefosine and after its extensive use. IMPORTANCE: Post-kala-azar dermal leishmaniasis (PKDL) patients, a key source of Leishmania donovani parasites, hinder eliminating visceral-leishmaniasis. Assessment of the susceptibility of PKDL isolates to antimony, miltefosine (MIL), and amphotericin-B indicated that recent isolates remain susceptible to antimony, enabling its use with other drugs for treating PKDL.

Impact of fibromyalgia severity on patients mood, sleep quality, and quality of life.

Objectives: Fibromyalgia syndrome (FMS) is characterized by persistent widespread pain which greatly impacts the quality of life (QOL). Pain not only limits patients' daily activities but also restricts their social activities further leading to depression, anxiety, and stress. The present cross-sectional study elucidated the association of sleep quality and mood with increasing symptom severity of fibromyalgia and its impact on the QOL of fibromyalgia patients. Materials and Methods: Hundred adult fibromyalgia patients diagnosed by the American College of Rheumatology 2010 criteria were evaluated for: sleep - using the Pittsburgh sleep quality index, QOL by SF-36, pain-visual analog scales (VASs) and global pain scale (GPS), mood-depression, anxiety, stress scale-21, somatic symptoms, anxiety and depression - by patients health questionnaire somatic, anxiety, and depressive symptom scales (PHQ-SADS), and FMS severity was evaluated using fibromyalgia impact questionnaire (FIQR). Results: The mean pain score was 6.80 ± 1.58 on VAS and 54.10 ± 14.33 on GPS. FIQR score was 50.62 ± 13.68, mean sleep quality was poor (9.30 ± 3.88), and depression, anxiety, and stress scores were increased (10.04 ± 4.59, 8.33 ± 4.48, and 10.75 ± 4.66). An increasing trend of depression, anxiety, stress, and somatoform symptoms was observed with an increase in the severity of FMS when patients were compared according to FMS severity scores. Sleep also deteriorated with increasing severity of FMS from 5.66 ± 1.92 in mild FMS to 12.0 ± 3.41 in highly severe FMS patients. The QOL too deteriorated in all the domains with increasing severity. Conclusion: With the increasing severity of fibromyalgia, not only does the pain increase but mood and sleep quality also deteriorate, which further impacts the QOL of FMS patients. Thus, comorbid mood derangements must also be screened and addressed for maximum benefit of the patients.

Evolution of Mn-Bi2O3 from the Mn-doped Bi3O4Br electro(pre)catalyst during the oxygen evolution reaction.

Mn-doped Bi3O4Br has been synthesized using a solvothermal route. The undoped Bi3O4Br and Mn-Bi3O4Br materials possess orthorhombic unit cells with two distinct Bi sites forming a layered atomic arrangement. The shift in the (020) plane in the powder X-ray diffraction (PXRD) pattern confirms Mn-doping in the Bi3O4Br lattice. Elemental mapping indicated 7% Mn doping in the Bi3O4Br lattice structure. A core-level X-ray photoelectron study (XPS) indicates the presence of BiIII and MnII valence-states in Mn-Bi3O4Br. Doping with a cation (MnII) containing a different charge and ionic radius resulted in vacancy/defects in Mn-Bi3O4Br which further altered its electronic structure by reducing the indirect band gap, beneficial for electron conduction and electrocatalysis. The irreversible MnII to MnIII transformation at a potential of 1.48 V (vs. RHE) precedes the electrochemical oxygen evolution reaction (OER). The Mn-doped electrocatalyst achieved 10 mA cm-2 current density at 337 mV overpotential, while the pristine Bi3O4Br required 385 mV overpotential to reach the same activity. The pronounced OER activity of the Mn-Bi3O4Br sample over the pristine Bi3O4Br highlights the necessity of MnII doping. The superior activity of the Mn-Bi3O4Br catalyst over that of Bi3O4Br is due to a low Tafel slope, better double-layer capacitance (Cdl), and small charge-transfer resistance (Rct). The chronoamperometry (CA) study depicts long-term stability for 12 h at 20 mA cm-2. An electrolyzer fabricated as Pt(-)/(+)Mn-Bi3O4Br can deliver 10 mA cm-2 at a cell potential of 2.05 V. The post-CA-OER analyses of the anode confirmed the leaching of [Br-] followed by in situ formation of Mn-doped Bi2O3 as the electrocatalytically active species. Herein, an ultra-low Mn-doping into Bi3O4Br leads to an improvement in the electrocatalytic performance of the inactive Bi3O4Br material.

Development and optimization of Clitoria teratea synthesized silver nanoparticles and its application to nanogel systems for wound healing.

OBJECTIVE: The present research deals with sequential optimization strategy based on Central Composite Design to optimize the process variables for efficient production of Clitoria teratea (CLT) synthesized silver nanoparticles (AgNPs) using biological synthesis. METHODS: Two substantial factors influencing the dependent variables viz UV-visible absorbance, particle size, zeta potential and polydispersity index (PDI) were identified as NaOH concentration, RH concentration, temperature as independent variables. In-vitro and ex-vivo studies of prepared CLT-AgNPs gel and marketed gel were carried out using dialysis membrane and egg membrane, respectively. In addition, antimicrobial study was also performed on the bacterial strains. RESULTS: The particles size (114 nm), PDI (0.45), and zeta potential (-29.5 mV) of optimized formulation were found, respectively. In-vitro profile of AgNPs from prepared CLT-AgNPs gel was noted (95.6%) in 8 h. It was found that the prepared CLT-AgNPs gel stimulates fibroblast and agranulocytosis development resulting better and timely wound healing. CONCLUSIONS: The prepared CLT-AgNPs gel can be as a potential substitute in the management and treatment of acute and chronic wounds.

Raman spectroscopy and its plasmon-enhanced counterparts: A toolbox to probe protein dynamics and aggregation.

Protein unfolding and aggregation are often correlated with numerous diseases such as Alzheimer's, Parkinson's, Huntington's, and other debilitating neurological disorders. Such adverse events consist of a plethora of competing mechanisms, particularly interactions that control the stability and cooperativity of the process. However, it remains challenging to probe the molecular mechanism of protein dynamics such as aggregation, and monitor them in real-time under physiological conditions. Recently, Raman spectroscopy and its plasmon-enhanced counterparts, such as surface-enhanced Raman spectroscopy (SERS) and tip-enhanced Raman spectroscopy (TERS), have emerged as sensitive analytical tools that have the potential to perform molecular studies of functional groups and are showing significant promise in probing events related to protein aggregation. We summarize the fundamental working principles of Raman, SERS, and TERS as nondestructive, easy-to-perform, and fast tools for probing protein dynamics and aggregation. Finally, we highlight the utility of these techniques for the analysis of vibrational spectra of aggregation of proteins from various sources such as tissues, pathogens, food, biopharmaceuticals, and lastly, biological fouling to retrieve precise chemical information, which can be potentially translated to practical applications and point-of-care (PoC) devices. This article is categorized under: Therapeutic Approaches and Drug Discovery > Emerging Technologies Diagnostic Tools > Diagnostic Nanodevices Nanotechnology Approaches to Biology > Nanoscale Systems in Biology.

Cassia fistula galactomannan stabilized copper nanocatalyst as an efficient, recyclable heterogeneous catalyst for the fast clickable [3+2] Huisgen cycloadditions in water.

In this study, we have first time investigated the synthesis of copper nanocatalyst by using biopolymer galactomannan, naturally extracted from Cassia fistula pods. The methodology involved for the preparation of copper nanocatalyst is economical, efficient, environment friendly, and did not involve further processing for stabilization or reduction of copper nanoparticles. The morphology and structural characterization of the nanocatalyst was performed by using different techniques such as FT-IR, 1H NMR, SEM, EDX, HR-TEM, XRD, XPS, ICP-MS, BET, and TGA analysis. The prepared copper nanocatalyst is applied for the click [3+2] Huisgen cycloadditions of various azides and alkynes, employing water as environmentally benign solvent. In comparison to earlier reported methods, our method requires lowest catalyst loading, less reaction time, excellent yields and have wide substrate scope. Additionally, the catalyst was easily recovered by simple filtration and recycled at least ten consecutive times without any appreciable loss of efficiency and selectivity. The effect of mannose and galactose (Man/Gal) ratio of Cassia fistula galactomannan on the catalytic activity were also investigated.

Red cell abnormalities characterized by ektacytometry in children with cholestasis.

BACKGROUND: Spur-cell anemia sometimes accompanies cholestasis. We postulated that even in the absence of spur-cells, cholestasis might alter red blood cell (RBC) osmotic fragility and deformability. Therefore, we assessed these RBC measures by ektacytometry in pediatric patients. METHODS: We conducted a single center, prospective, cross-sectional investigation of RBC membrane characteristics by ektacytometry in pediatric patients with intra- and extrahepatic cholestasis followed at Cincinnati Children's Hospital Medical Center. We measured red cell membrane fragility and deformability in 17 patients with cholestasis and 17 age-matched controls without cholestasis. RESULTS: Patients with cholestasis had decreased RBC osmotic fragility compared to controls, with a significant left shift in Omin, indicating increased RBC surface-to-volume ratio. One showed spur cell morphology. However, the other 16 had no spurring, indicating that ektacytometry is a sensitive method to detect RBC membrane abnormalities. Left shift of Omin positively correlated with serum conjugated bilirubin levels and even more negatively with serum vitamin E concentration. CONCLUSIONS: This study suggests that subclinical red blood cell membrane abnormalities exist in most pediatric patients with cholestasis, increasing risk for hemolysis when subjected to oxidative stress. Hence minimizing pro-oxidants exposure and maximizing antioxidant exposure is advisable for this group. GOV IDENTIFIER: NCT05582447 https://clinicaltrials.gov/ct2/show/NCT05582447?cond=Cholestasis&cntry=US&state=US%3AOH&city=Cincinnati&draw=2&rank=2 . IMPACT: Spur cell anemia due to decreased red cell osmotic fragility and decreased deformability has been reported among patients with cholestasis. Ektacytometry is a reliable, reproducible method to measure red cell osmotic fragility and deformability. Few data describe red cell osmotic fragility or deformability in patients with cholestasis who may or may not have spur cell anemia. Ektacytometry shows that red cell osmotic fragility and deformability are decreased in many children with cholestasis even when spur cell anemia has not yet occurred. Factors associated with decreased osmotic fragility include elevated serum bilirubin, elevated serum bile acids, and decreased serum vitamin E.

Impact of school start time and sleep pattern of adolescents on their mood and sleep quality.

Objective: The physiological delay in bedtime among adolescents, compounded with the early start of school, results in insufficient sleep, especially on school days. The present study compared the sleep pattern and moods of students attending two schools with different start timing. Materials and Methods: The study involved adolescents from two schools with different start times: School A (7 am) and School B (8 am). Pittsburgh Sleep Quality Index, Depression Anxiety Stress Scales-21, and Pediatric Daytime Sleepiness Scale questionnaires were used to assess students' mood, sleep duration, sleep quality, and daytime sleepiness. The clinical trial registry number is CTRI/2022/06/043556. Result: A total of 640 students (mean age 13.7 ± 2.0 years; 47.5% male) participated in this study. Students from School B had longer sleep duration, with 72.9% reporting sleep deprivation compared to 87.1% of School A (P = 0.00001). School A students reported having (P ≤ 0.001) higher daytime sleepiness, higher daytime dysfunction (P = 0.023), and poorer sleep quality. Students at School A scored higher for all mood derangements, with significantly higher scores for depression (P = 0.041). Conclusion: The study illustrates that though not much differences are observed in the bedtime of adolescents of the two schools, however, due to the early school start time of School A, students have to compulsorily wake up early, leading to higher sleep deprivation and greater mood derangements among them.

Translation of Parkinson's Disease Sleep Scale-2 (PDSS-2) in Hindi (H-PDSS-2) and its Validation for Assessment of Sleep Disturbances among Indian Parkinson's Disease Patients.

Background and Objective: Parkinson's disease sleep scale-2 (PDSS-2) is a reliable sleep assessment tool which has been validated in several languages. As sleep problems have a great impact on the quality of life of Parkinson's disease patients, we aimed to translate and validate PDSS-2 in Hindi for its wider use among Hindi-speaking Indian patients. Our study objective was to translate PDSS-2 in Hindi (H-PDSS-2) and to assess the psychometric properties of H-PDSS-2 questionnaire for its use in Hindi-speaking Indian PD patients. Secondly, we aimed to compare the results with those of the other language PDSS-2 validation studies. Material and Methods: This study was done in two phases, enrolling 16 patients and 16 controls in the first/translation phase for assessment of internal consistency and discriminative power of PDSS-2. The test-retest reliability was determined in the second phase on 35 Parkinson's disease patients who were followed-up at an interval of 7-10 days. Results: No difficulties were faced by the patients and controls in the first phase, and internal consistency of the scale was good (Cronbach's alpha = 0.804). There was no significant difference in total H-PDSS-2 score at baseline 16.86 ± 10.59 and on retest 16.40 ± 9.54, suggesting good reliability. Intraclass correlation coefficients ranged from 0.710 to 0.901, and precision was 2.82 over the period of 7-10 days. Subdomains of H-PDSS-2 had moderate/high internal validity, and they showed significant correlation with Unified PD Rating Scale (UPDRS) and HY disease scale. Conclusion: H-PDSS-2 is equivalent to the original PDSS-2 for tested psychometric attributes. Its use among Indian Parkinson's disease patients will help in the comprehensive assessment of sleep problems among PD patients.

Assessment of Cardiac Autonomic Function in Women With Polycystic Ovary Syndrome Through Ewing's Battery, Heart Rate Variability Analysis, and Composite Autonomic Symptom Score-31 Scale.

Introduction Polycystic ovary syndrome (PCOS) is a frequently occurring endocrine condition prevalent in women of reproductive age characterized by chronic anovulation, hyperandrogenism, insulin resistance, and a low-grade inflammatory state. Patients with PCOS are more vulnerable to developing cardiac and metabolic co-morbidities. Sympathetic overactivity is also reported in PCOS patients. Objective This study aimed to assess cardiac autonomic function in PCOS by Heart Rate Variability Analysis, Ewing's Test, and Composite Autonomic Symptom Scale-31 (COMPASS-31). Methods Thirty female PCOS patients and 30 age-matched control females were enrolled in the study. Both cases and controls were subdivided into sub-groups based on body mass index (BMI) and waist-to-hip ratio (WHR). The cardiac autonomic functions were assessed by the COMPASS-31 questionnaire, Ewing's battery tests, and short-term heart rate variability analysis. Results There was no significant difference in age, BMI, and WHR of both groups. Additionally, cases had a significantly higher low frequency to high frequency (LF/HF) ratio and COMPASS-31 score and also reported more derangement in Ewing's battery test, indicating cardiac autonomic dysfunction in PCOS patients. Conclusion Patients with PCOS are more prone to developing cardiac and metabolic co-morbidities. Early assessment of cardiac autonomic function can prevent future complications with timely interventions. Altered autonomic function in PCOS patients can be due to hyperandrogenism and insulin resistance.

Exaggerated response to pattern reversal visual evoked potential among migraineurs.

OBJECTIVE: Visual evoked potential recording has reported ambiguous results among migraineurs, thus the present study explored the association of check-size and reversal rates on the latency and amplitude of pattern reversal VEP among migraineurs. METHOD AND MATERIAL: Monocular VEP responses for both eyes were recorded in 133 migraineurs and 111 controls. Checkerboard pattern with phase reversal frequency of 0.5, 1, 2 and 4 Hz and check-size of 16 × 16, 32 × 32, 64 × 64 and 128 × 128, i.e. spatial frequency of 0.475, 1.029, 2.056 and 4.112 cycle per degree (cpd) were used to record 100 responses each. Three-minutes gap was given after change of reversal frequency to a higher rate for next cycle of 4 check-size records. RESULT: A linear increase in latencies was observed with decreasing check-size in both groups, but migraineurs had significantly higher latencies at a given reversal rate. Amplitudes A1 and A2 were higher among migraineurs and amplitude A2 showed an inverted 'U' shaped trend with maximum amplitude at 32 × 32 check size (1.029 cpd) in both groups, with an exaggerated response among migraineurs. Check-size 32 × 32 i.e. spatial frequency of 1.029 behaves differently than other larger or smaller check-sizes. CONCLUSION: Variable VEP response for different visual stimuli may be due to differential activation of respective retinocortical pathways and cortical areas. The highest amplitude at modest check-size suggests a contributory role of foveal-parafoveal fibres in migraineurs. Exaggerated physiological response to visual stimuli may be responsible for higher amplitudes and prolonged latencies among migraineurs.

Exaggerated physiological VEP response as higher amplitudes and prolonged latencies, among migraineurs may be due to differential activation of respective retinocortical pathways and cortical areas.

Application of CL Detect™ rapid test for diagnosis and liposomal amphotericin B for treatment of cutaneous leishmaniasis: A retrospective analysis from a tertiary care centre in a non-endemic area in India.

Background Increasing urbanisation has led to the occurrence of cutaneous leishmaniasis (CL) in new areas, which was otherwise localised to endemic areas. Healthcare workers should be made aware of this entity to ensure clinical suspicion of CL and investigations needed to confirm CL. The article describes patients seen at a tertiary hospital in Delhi. Aims To establish the utility of the CL Detect Rapid test as a diagnostic tool and the efficacy of Liposomal Amphotericin B (LAmB) for the complete cure of CL patients. Methods Data of patients of CL (n = 16) was retrospectively analysed concerning diagnosis and treatment. Diagnosis rested on histopathology, real-time PCR, and CL Detect Rapid Test. Speciation of the parasite was based on the Internal transcribed spacer-I gene. Patients were treated with LAmB (i.v., 5 mg/kg up to three doses, five days apart). Results A positivity of 81.3% (95%CI, 54.4-96) was observed for CL Detect Rapid test in comparison with 100% (95%CI, 79.4-100.0) for real-time PCR and 43.8% (95%CI, 19.8-70.1) for microscopy/histopathological examination. L. tropica was the infective species in all cases. All the patients treated with LAmB responded to treatment, and 9/10 patients demonstrated complete regression of lesions, while one was lost to follow-up. Limitations It is a retrospective study, and the data includes only confirmed cases of CL at a single centre. Conclusion This study highlights the utility of CL Detect as a promising diagnostic tool and the efficacy of LAmB for the complete cure of CL.

Effectiveness of rehabilitation strategies in primary fibromyalgia syndrome: A systematic review and meta-analysis.

Objectives: The aim of this review was to (1) summarize evidence on the effectiveness of rehabilitation strategies in fibromyalgia syndrome (FMS) and (2) determine the most effective rehabilitation strategy for reducing pain and depression in people with FMS. Data Sources: PubMed, Ovid (Sp), and Cochrane search engines were used for identifying relevant studies done up to 1st of July 2022. Study Selection: Randomized control trials (RCTs) that have a passive control group and an active control group were included in this review for primary and secondary aim, respectively. The primary outcome measures were pain and depression. Secondary outcome was one from the sleep or fatigue or healthy related quality of life (HRQOL). Data Extraction: Two researchers independently selected the studies and extracted the key information. Data Synthesis: A total of 25 RCTs were included. Studies with passive control group showed moderate to large positive effects on pain (standard mean difference -0.65, 95% confidence interval -0.93 to -0.38; I2 = 72%) and HRQOL (MD -5.40, 95% CI -10.17 to -0.62; I2 = 74%) but were not statistically significant for sleep, fatigue, and depression. Furthermore, on subgroup analysis studies with a short term protocol showed significant effects on pain only, whereas studies with long term protocols showed positive effects on pain and HRQOL only, but no statistical significance at the time of post-trial follow-up. Studies with active control groups gave non-significant results except where there was mixed exercises, which showed a positive effect (mean difference -4.78, 95% CI -7.98 to -1.57; I2 = 0%) for HRQOL. Conclusion: All rehabilitation strategies were effective for pain and HRQOL, and had a marginal effect on depression, sleep, and fatigue but efficacy was not maintained at the time of post-trial follow-up. However, in this review, we could not differentiate any rehabilitation strategies for the best among those used in the included studies.

Outbreak investigation of Dengue like fever in rural area of Rajasthan.

During October 2020, suddenly many cases were reported with Dengue like Illness in Sahawa village, Rajasthan. Blood samples collected from 68 patients were tested for Dengue NS1 antigen and IgM antibodies for Dengue, Chikungunya, Scrub typhus, Leptospira and Brucella by ELISA, Dengue, Chikungunya and Zika viral RNA by multiplex Polymerase Chain Reaction (PCR), 41.17% samples were positive for Dengue; 25% were positive by Dengue PCR, 17.64% for NS1 Ag,14.70% for IgM ELISA, 20.58% were positive for antibodies either for Scrub typhus (4.41%), Leptospira (7.35%) or Brucella (10.29%). Dengue was seen in 41.17% cases and other etiological agents in 20.58% cases.

Antibacterial and Antibiofilm Properties of the Alexidine Dihydrochloride (MMV396785) against Acinetobacter baumannii.

Antibiotic-resistant Acinetobacter baumannii infections among patients in hospital settings are rising at an alarming rate. The World Health Organization has designated carbapenem-resistant A. baumannii as a priority pathogen for drug discovery. Based on the open drug discovery approach, we screened 400 compounds provided as a Pandemic Response Box by MMV and DNDi to identify compounds with antibacterial and antibiofilm activity against two A. baumannii reference strains using a highly robust resazurin assay. In vitro screening identified thirty compounds with MIC ≤ 50µM having growth inhibitory properties against the planktonic state. Five compounds, with MMV IDs MMV396785, MMV1578568, MMV1578574, MMV1578564, and MMV1579850, were able to reduce metabolically active cells in the biofilm state. Of these five compounds, MMV396785 showed potential antibacterial and antibiofilm activity with MIC, MBIC, and MBEC of 3.125 µM, 12.5, and 25-100 µM against tested A. baumannii strains, respectively, showing biofilm formation inhibition by 93% and eradication of pre-formed biofilms by 60-77.4%. In addition, MMV396785 showed a drastic reduction in the surface area and thickness of biofilms. Further investigations at the molecular level by qRT-PCR revealed the downregulation of biofilm-associated genes when exposed to 50 µM MMV396785 in all tested strains. This study identified the novel compound MMV396785 as showing potential in vitro antibacterial and antibiofilm efficacy against A. baumannii.

Signaling pathways and molecular process of natural polyphenols in the amelioration of inflammatory bowel disease: A privileged scaffold in new drug discovery.

BACKGROUND: GIT is seriously affected by inflammatory bowel disease (IBD), which is characterized by extreme inflammation and an imbalance in a person's healthy life span. The frequency of occurrence of such chronic diseases as IBD would continue to increase. In the past decade, increasing attention has been paid to polyphenols from natural sources have been shown to serve as successful therapeutic agents for altering the signalling pathways linked to IBD and oxidative stress. METHODS: We conducted a structured search for peer-reviewed research articles using the various keywords in bibliographic databases. By using common tools and a deductive qualitative content analysis technique, the quality of the retrieved papers and the distinctive findings of the articles included in the study were evaluated. RESULTS: Notably, experimental and clinical evidence has proved that natural polyphenols could act as a targeted modulator to play a key role in the prevention or treatment of IBD. Polyphenol phytochemicals have shown noticeable alleviative effects by acting on the TLR/NLR, and NF-κB signaling pathway in intestinal inflammation. CONCLUSION: This study examines the potential of polyphenols for treating IBD, with an emphasis on modulating cellular signalling mechanisms, regulating the balance of gut microbiota, and restoring the epithelial barrier. The available evidence concluded that the utilization of polyphenol-rich sources could control inflammation, mucosal healing, and positive benefits with minimal side effects. Even though additional study is required in this area, particularly that which focuses on the interactions, connections, and precise mechanisms of action linking polyphenols and IBD.