The Efficacy of Thumb Spica Casting With or Without Corticosteroid Injection for De Quervain's Tenosynovitis.

Background and objective De Quervain's tenosynovitis is a highly prevalent wrist pathology primarily caused by chronic thumb overuse. Its management typically begins with conservative methods, progressing to corticosteroid injections or surgery if necessary. This study compares the efficacy of thumb spica casting plus corticosteroid injection versus casting alone for treating De Quervain's tenosynovitis. Materials and methods This quasi-experimental study was conducted at the Department of Orthopaedics, Khyber Teaching Hospital, Peshawar, and enrolled adults aged 18-50 who presented with De Quervain's tenosynovitis. Patients were assigned to receive either corticosteroid injection plus thumb spica cast (Group A) or thumb spica cast alone (Group B). The primary outcome assessed the treatment success rate, while the secondary outcome evaluated the treatment effectiveness using visual analog scale (VAS) scores and Quick Disabilities of Arm, Shoulder, and Hand (QuickDASH). Results Of the initial 65 patients enrolled, 61 completed the study. Group A demonstrated a significantly higher treatment success rate (83.9%, n=26) compared to Group B (40%, n=12) (p<0.001). Pain reduction, as measured by VAS, was markedly greater in Group A (8.4 ± 1.0 to 0.4 ± 0.5) than in Group B (9.0 ± 0.8 to 5.9 ± 1.3) (p<0.001). Similarly, functional improvement assessed by QuickDASH favored Group A (89.6 ± 8.2 to 8.9 ± 6.8) over Group B (84.3 ± 10.1 to 49.1 ± 12.3) (p<0.001). No serious adverse effects related to treatments were noted in either of the groups. Conclusions This study supports the superiority of thumb spica casting along with local corticosteroid injection over casting alone for treating De Quervain's tenosynovitis. The combined approach led to significantly better pain relief and functional outcomes, highlighting its effectiveness as a treatment option despite the positive outcomes observed with casting alone.

Assessment of Knowledge, Attitude, and Practice Regarding Colorectal Carcinoma Screening Among Healthcare Personnel.

BACKGROUND: Colorectal carcinoma (CRC) is a rising issue worldwide, with high morbidity and mortality rates. It is the third most common cause of death globally. Early diagnosis can lead to prevention and treatment, making it crucial for healthcare professionals to have proper knowledge about CRC screening. AIMS AND OBJECTIVES: This study aimed to assess the level of awareness, identify knowledge gaps, and update the knowledge of healthcare workers. METHODS:  This descriptive cross-sectional study was conducted from May to October 2023, in multiple tertiary care hospitals of Khyber Pakhtunkhwa, Pakistan. Responses were collected manually through a designed proforma of questionnaires. RESULTS: A total of 164 participants (137 male and 27 female) took part in our study. Among the participants, 92.1% (n = 151) were aware that colonoscopy is used for CRC screening. Other screening methods known to them included a fecal occult blood test (FOBT) (65.9%, n = 108), flexible sigmoidoscopy (48.2%, n = 79), stool DNA test (31.1%, n = 51), and virtual colonoscopy (34.1%, n = 56). Only 6.1% (n = 10) routinely recommended CRC screening for all patients, 22.6% (n = 37) recommended it occasionally, and 71.3% (n = 117) rarely or never recommended it. Regarding factors influencing the recommendation of CRC screening, 83.5% (n = 137) cited family history of CRC as the major factor, followed by patient age (68.3%, n = 112), availability of screening facilities (46.3%, n = 76), patient's overall health status (37.2%, n = 61), and patient's preference (20.7%, n = 34). CONCLUSION: This study concluded that only a small proportion of healthcare personnel regularly recommend CRC screening. In addition, a small proportion are familiar with CRC screening guidelines, although most are well-informed about the various investigations used for screening.

Comparison of Partial Meniscectomy With Meniscal Repair With Respect to Functional Outcome.

Introduction Meniscus tear is a commonly encountered sports-related injury requiring surgical intervention due to knee mobility dysfunction and discomfort. Previously, it has been thought that these are non-functional vestigial structures and they used to be excised commonly. Recent studies have shown that meniscal repair gives superior results when compared with partial meniscectomy. Methods This quasi-experimental study was conducted at the Orthopedics Department, Khyber Teaching Hospital, Peshawar, Pakistan. A total of 92 patients of both genders with meniscal injuries were included. Forty-six of them underwent meniscal repair (Group A), and 46 underwent partial meniscectomy (Group B). Functional outcome was noted after 12 weeks and recorded. Results The age range was from 18 to 50 years with a mean of 28.630±6.64 years in Group A and 29.630±8.12 years in Group B. Functional outcome was excellent in 44 (95.7%) patients who underwent meniscal repair as compared to 23 (50%) patients who underwent partial meniscectomy (P= 0.000). Conclusion It is concluded that meniscal repair should be pursued over partial meniscectomy when surgically treating meniscal tears.

Biocompatible carbon quantum dots as versatile imaging nanotrackers of fungal pathogen - Candida albicans.

Aim: The development of carbon quantum dots (C-QDs) as nanotrackers to understand drug-pathogen interactions, virulence and multidrug resistance. Methods: Microwave synthesis of C-QDs was performed using citric acid and polyethylene glycol. Further, in vitro toxicity was evaluated and imaging applications were demonstrated in Candida albicans isolates. Results: Well-dispersed, ultra small C-QDs exhibited no cyto/microbial/reactive oxygen species-mediated toxicity and internalized effectively in Candida yeast and hyphal cells. C-QDs were employed for confocal imaging of drug-sensitive and -resistant cells, and a study of the yeast-to-hyphal transition using atomic force microscopy in Candida was conducted for the first time. Conclusion: These biocompatible C-QDs have promising potential as next-generation nanotrackers for in vitro and in vivo targeted cellular and live imaging, after functionalization with biomolecules and drugs.

Scientists have used radiolabeled drugs and radioactive tracking agents for the imaging and study of drug resistance in microbial pathogens. But, these radiolabeled drugs or radiotrackers pose health hazards and environmental risks. However, such limitations can be overcome by designing nontoxic, environment-friendly, nanotechnology-based fluorescent imaging agents. This study demonstrates the development and application of cost-effective, nontoxic carbon-based quantum dots for imaging of drug-sensitive and -resistant microbial strains and transition to different morphological forms (yeast-to-hyphae transition) in fungal pathogens. The results demonstrated the suitability of carbon quantum dots as next-generation nano-based bioimaging/tracking agents for cellular imaging. The availability of such nontoxic fluorescent tracking agents is likely to offer promising solutions in therapeutics and diagnostics by providing insight into various mechanisms and functional links related to drug resistance, virulence and pathogenicity.

Surgical Strategies for Ingrown Toenails: A Comprehensive Review of Techniques, Outcomes, and Advancements.

Ingrown toenail (IGTN), known as onychocryptosis or unguis incarnatus, is a painful condition affecting the big toe, with symptoms including pain, inflammation, and infection. This review explores surgical options for IGTN, categorized into altering the nail plate or diminishing periungual tissues. Conservative treatments alleviate early-stage symptoms, while surgical interventions are reserved for severe cases. Various surgical techniques are discussed, such as the Winograd technique, Vandenbos procedure, chemical matricectomy, radiofrequency ablation, bipolar diathermy, carbon dioxide laser ablation, Zadik's procedure, Howard-Dubois procedure, Super U procedure, Noël's procedure, knot technique, and toenail paronychium flap. The choice of procedure depends on the severity and recurrence of IGTN.

Passivity-based Rieman Liouville fractional order sliding mode control of three phase inverter in a grid-connected photovoltaic system.

Photovoltaic (PV) system parameters are always non-linear due to variable environmental conditions. The Maximum power point tracking (MPPT) is difficult under multiple uncertainties, disruptions and the occurrence of time-varying stochastic conditions. Therefore, Passivity based Fractional order Sliding-Mode controller (PBSMC) is proposed to examine and develop a storage function in error tracking for PV power and direct voltage in this research work. A unique sliding surface for Fractional Order Sliding Mode Control (FOSMC) framework is proposed and its stability and finite time convergence is proved by implementing Lyapunov stability method. An additional input of sliding mode control (SMC) is also added to a passive system to boost the controller performance by removing the rapid uncertainties and disturbances. Therefore, PBSMC, along with globally consistent control efficiency under varying operating conditions is implemented with enhanced system damping and substantial robustness. The novelty of the proposed technique lies in a unique sliding surface for FOSMC framework based on Riemann Liouville (R-L) fractional calculus. Results have shown that the proposed control technique reduces the tracking error in PV output power, under variable irradiance conditions, by 81%, compared to fractional order proportional integral derivative (FOPID) controller. It is reduced by 39%, when compared to passivity based control (PBC) and 28%, when compared to passivity based FOPID (EPBFOPID). The proposed technique led to the least total harmonic distortion in the grid side voltage and current. The tracking time of PV output power is 0.025 seconds in PBSMC under varying solar irradiance, however FOPID, PBC, EPBFOPID, have failed to converge fully. Similarly the dc link voltage has tracked the reference voltage in 0.05 seconds however the rest of the methods either could not converge, or converged after significant amount of time. During solar irradiance and temperature change, the photovoltaic output power has converged in 0.018 seconds using PBSMC, however remaining methods failed to converge or track fully and the dc link voltage has minimum tracking error due to PBSMC as compared to the other methods. Furthermore, the photovoltaic output power converges to the reference power in 0.1 seconds in power grid voltage drop, whereas other methods failed to converge fully. In addition power is also injected from the PV inverter into the grid at unity power factor.

Mutational analysis of CRYAA gene of cataract and investigating risk assessment factors responsible for eye diseases in district buner, KPK, Pakistan.

This research has been designed to analyze the risk factors of major eye diseases and the genetic alterations contributing to the manifestation of such disease. For this purpose, data was collected from 256 patients diagnosed by an ophthalmologist by using a specialized questionnaire. Blood samples were collected from 100 patients to perform a genetic investigation of cataracts. Whole genomic DNA was extracted from blood samples via the phenol-chloroform method. The purified DNA was used as the template for the amplification of about 400 bp fragments amplifying exons 1 and 2 of the CRYAA gene. The statistical analysis showed that 68% of individuals were blind due to cataracts. During molecular analysis, nucleotide sequences obtained have resulted in one silent mutation that occured at 20 positions in exon 2. It was replacing A>G which in turn substitutes the Lysine at position 70 for Arginine. It was interpreted by statistical analysis that this mutation did not result in a significant change in the CRYAA gene. In addition, protein analysis showed no significant changes in the structure of normal and mutated genes. At last, it is concluded that environmental risk factors play a major role in the studied diseases as compared to genetic factors. It is recommended to extend the study to a larger population to study all exons of the CRYAA gene as well as develop better estimates of the magnitude of the problems of visual loss and eye diseases in the Pakistani population.

Aberrations in the progesterone pathway and the Th1/Th2 cytokine dichotomy - An evaluation of RPL predisposition in the northeast Indian population.

PROBLEM: Recurrent pregnancy loss (RPL) is the spontaneous loss of two or more consecutive pregnancies prior to 20 weeks of gestation, occurring in 1% of the reproductive-age population. It is a major cause of infertility in India with a staggering 7.46% prevalence rate. METHOD OF STUDY: Blood and product of conception (POCs) from RPL cases (n = 65) were enrolled for this study, along with cases of medically terminated pregnancy (MTP, n = 80) and term delivery cases (n = 90) as control. ELISA for progesterone and progesterone induced blocking factor (PIBF) levels was carried out, followed by mRNA expression analysis of progesterone receptor isoform B (PR-B) and its downstream immunomodulatory effectors, namely, PIBF, IL-10 and IL-12. Screening of PROGINS haplotype of PR gene and PIBF polymorphism were also conducted to correlate with their respective gene expression profiles. RESULTS: Serum progesterone level was found to be comparable in the RPL and MTP cases. Although the mRNA expression of PR-B was found to be downregulated in the RPL cases, no significant PROGINS haplotype was observed. Presence of a single nucleotide polymorphism (SNP) in the PIBF gene (rs1372000) was more in healthy controls compared to RPL cases. Serum PIBF levels were found to be lower in the RPL cases with a resultant increase in IL-12 and a decrease in IL-10 mRNA expression in these cases. CONCLUSIONS: This study indicates that progesterone, acting through PIBF, modulates the immunological state of pregnancy to be Th1-biased in RPL, indicative of a pro-inflammatory, labour-like state not desired for a healthy pregnancy.

Spectroscopic investigations on fungal aspartic protease as target of gallic acid.

Proteases are a major virulence factor in pathogenic fungi and can serve as a potential therapeutic target. The interaction of gallic acid (GA) with Aspartic fungal protease (PepA) was investigated using biophysical and in silico approaches. UV-Vis and fluorescence spectroscopy showed complex formation and static quenching of PepA by GA with Ka of 7.4 × 105 M-1 and stoichiometric binding site (n) of 1.67. CD-spectroscopy showed marked changes in helical content and synchronous fluorescence spectra measurements indicated significant changes in the microenvironment around tryptophan residues in the GA-PepA complex. Outcomes of Isothermal Titration Calorimetry (ITC) measurement and molecular modelling studies validated the spectroscopic results. The binding of GA to Human Serum albumin (HSA) was moderate (Ka = 1.9 × 103 M-1) and did not cause structural disruption of HSA. To conclude, gallic acid is strongly bound to fungal protease leading to structural disruption and inhibition whereas HSA structure was largely conserved. Gallic acid thus appears to be a potential therapeutic agent against fungal proteases.

Epidemiological analysis of Paramphistomum species in Ruminants in selected Districts of Khyber Pakhtunkhwa (KPK), Pakistan

This epidemiological study was conducted to compare the climatic conditions of four different districts of Khyber Pakhtunkhwa, Pakistan, in terms of the prevalence of parasitic infection Paramphistomum in cows and buffaloes. A total of 2400/cows and buffaloes (200/per month and 50/per district) fecal samples were collected. The samples were examined for Paramphistomum egg contamination by direct microscopic examination and sedimentation methods. The infectivity ratio was 17.5% in cows and 17% in buffaloes; the higher rate of infection was recorded in autumn with 41% in cows and 36% in buffaloes. Whereas the lowest ratio was 6.5% in cows and 7% in buffaloes recorded during spring. It was also noted that a high rate of prevalence was recorded in older animals (higher than 2 years of age) than younger (less than 2 years of age), while gender-wise, it was observed that male animals were more affected than females. Prevalence was higher in cows in Mardan district (19.30%) followed by Nowshera (19.10%) and Swabi (17.80%) districts while lowest in Charsadda district (13.80%) where in buffaloes the higher prevalence was recorded in Swabi (18.80%) followed by Mardan (18.60%) then Charsadda (16.80%) while lowest in Nowshera (13.80%).

Anti-fasciolic effect of raw seeds of Nigella sativa, Fumaria parviflora (aerial), in naturally infected Buffaloes

In the present study Nigella sativa (seeds) and Fumaria parviflora (aerial), were used to treat buffaloes naturally infected with fasciolosis and their efficacy (%) was compared. In vivo, pre-and post-treatment (50 mg, 100 mg, and 150 mg/ kg body weight of the two medicinal plants) fecal egg counts were determined following standard fecal egg count reduction in buffaloes (Babulus sp.) of Nili Ravi breed naturally parasitized with Fasciola sp. The infected buffaloes were randomly divided into 3 main groups' i.e. A, B, and C. Animals in groups A and B were further subdivided into three subgroups i.e. A1, A2, A3; B1, B2, B3. Sub-groups A1 and B1 were given dose levels of 50mg/kg body weight, A2, and B2, 100mg while A3 and B3, 150mg/kg body weight of Nigella sativa (seeds) and Fumaria parviflora (aerial), respectively. Group C with infected animals served as a control. 2 medicinal plants has been found significantly (P<0.05) efficient (42-100%) and safe to use against fasciolosis.

Enhancing Documentation Precision in Ophthalmic Surgery: A Quality Improvement Project.

Background Effective clinical documentation, particularly operative notes, is essential for maintaining healthcare standards and fostering interdisciplinary communication. This study focuses on improving the quality of ophthalmic operative notes by adopting the Royal College of Surgeons (RCS) guidelines for good surgical practice. Methodology A retrospective cross-sectional audit at Khyber Teaching Hospital, Pakistan, assessed 138 operative notes against the RCS criteria. After an educational session and the placement of memory aids in operation theaters, a re-audit of 125 notes was conducted. Parameters were selectively applied based on relevance to specific cases, and omissions were discussed with the local ethical committee. Results The initial audit revealed deficiencies in 10 critical areas, with only three parameters exceeding 85% accuracy. The re-audit showed significant improvement across these parameters, achieving documentation of 85.3% of all criteria. Paired t-test results indicated a substantial difference in documentation quality before and after interventions. Conclusions A combined strategy involving surgeon education, memory aids, and adherence to established standards significantly enhances operative note quality. The study underscores the importance of sustained reinforcement mechanisms for continuous improvements in documentation practices.

Quercetin and resveratrol ameliorate nickel-mediated hypercontraction in isolated Wistar rat aorta.

PURPOSE: The ameliorative potential of quercetin and resveratrol on isolated endothelium-intact aortic rings incubated with nickel was examined. METHOD: The effect of varying concentrations of quercetin and resveratrol was investigated on isolated Wistar rat aortic rings using an organ bath system over vasoconstrictor phenylephrine (PE) at 1 µM. To delineate the mechanism of action, isolated aortic rings were pre-incubated with pharmacological modulators, such as verapamil 1 µM, apocynin 100 µM, indomethacin 100 µM or N-G-nitro-L-arginine methyl ester (L-NAME) 100 µM, separately, before incubation with 100 µM quercetin and 30 µM resveratrol. To assess the ameliorative and prophylactic potentials of quercetin and resveratrol, aortic rings were also incubated with quercetin or resveratrol for 40 min, followed by incubation with nickel for 40 min. RESULTS: At 100 µM, quercetin caused 29% inhibition of contraction, while resveratrol at 30 µM caused 55% inhibition of contraction in aortic rings compared with control. Aortic rings incubated with contractile modulators, such as verapamil, apocynin, indomethacin or N-G-nitro-L-arginine methyl ester (L-NAME), along with quercetin or resveratrol at their concentrations producing maximum relaxant effect, showed that both of these natural compounds exert their relaxant effect by inhibiting the generation of reactive oxygen species (ROS) from endothelial and smooth muscle cells, blocking voltage-gated calcium channels, and increasing the release of nitric oxide (NO). The mediation of hypercontraction by nickel is due to the increased ROS and the influx of calcium through voltage-dependent calcium channels. These natural compounds are shown to counter the nickel-induced effects, appearing as effective ameliorators. CONCLUSION: In this study, we found that quercetin and resveratrol act as ameliorators of nickel-mediated hypercontraction by decreasing ROS and enhancing NO release from endothelial cells.

Interaction of fungal lipase with potential phytotherapeutics.

Interaction of thymol, carvacrol and linalool with fungal lipase and Human Serum Albumin (HSA) have been investigated employing UV-Vis spectroscopy Fluorescence and Circular dichroism spectroscopy (CD) along with docking studies. Thymol, carvacrol and linalool displayed approximately 50% inhibition at 1.5 mmol/litre concentrations using para-nitrophenyl palmitate (pNPP). UV-Vis spectroscopy give evidence of the formation of lipase-linalool, lipase-carvacrol and lipase-thymol complex at the ground state. Three molecules also showed complex formation with HSA at the ground state. Fluorescence spectroscopy shows strong binding of lipase to thymol (Ka of 2.6 x 109 M-1) as compared to carvacrol (4.66 x 107 M-1) and linalool (5.3 x 103 M-1). Number of binding sites showing stoichiometry of association process on lipase is found to be 2.52 (thymol) compared to 2.04 (carvacrol) and 1.12 (linalool). Secondary structure analysis by CD spectroscopy results, following 24 hours incubation at 25°C, with thymol, carvacrol and linalool revealed decrease in negative ellipticity for lipase indicating loss in helical structure as compared with the native protein. The lowering in negative ellipticity was in the order of thymol > carvacrol > linalool. Fluorescence spectra following binding of all three molecules with HSA caused blue shift which suggests the compaction of the HSA structure. Association constant of thymol and HSA is 9.6 x 108 M-1 which along with 'n' value of 2.41 suggests strong association and stable complex formation, association constant for carvacrol and linalool was in range of 107 and 103 respectively. Docking results give further insight into strong binding of thymol, carvacrol and linalool with lipase having free energy of binding as -7.1 kcal/mol, -5.0 kcal/mol and -5.2 kcal/mol respectively. To conclude, fungal lipases can be attractive target for controlling their growth and pathogenicity. Employing UV-Vis, Fluorescence and Circular dichroism spectroscopy we have shown that thymol, carvacrol and linalool strongly bind and disrupt structure of fungal lipase, these three phytochemicals also bind well with HSA. Based on disruption of lipase structure and its binding nature with HSA, we concluded thymol as a best anti-lipase molecule among three molecules tested. Results of Fluorescence and CD spectroscopy taken together suggests that thymol and carvacrol are profound disrupter of lipase structure.

Exploration of microplastic pollution with particular focus on source identification and spatial patterns in riverine water, sediment and fish of the Swat River, Pakistan.

Microplastics (MPs) have been reported as an emerging xenobiotic organic pollutant in freshwater ecosystems and a universal hazard for ecosystems because of the rapid increase in global demand. The present study was conducted to explore MPs' occurrence, abundance and spatial distribution in sediment, water and Schizothorax plagiostomus samples, collected from the Swat River. ATR-FTIR spectroscopy was used for chemical characterization of visually identified MPs by using standard protocols such as digestion using H2O2, density separation using ZnCl2, vacuum filtration with borosilicate glass micro filter papers and digital microscopy using a stereomicroscope connected with a camera. Range of mass abundance of identified MPs in river sediments, river water, tributaries sediment and tributary water was found to be 0.6-2.5 mg kg-1, 0.7-3.8 mg L-1, 0.9-4.5 mg kg-1 and 0.6-1.1 mg L-1 respectively. Meanwhile, in Schizothorax plagiostomus digestive tracts samples, it was 0.6-1.9 mg per fish. Numeric abundance of MPs in all matrices was found to be tributary sediment (202 items per kg) > river water (192 items per L) > river sediment (182 items per kg) > fish (153 items per fish) > tributary water (92 items per L). MPs identified on the basis of morphology in all matrices were found to be fragments > fibers > pellets > films > foams. MPs were dominant in all urban stations while their spatial distribution along with the study site was heterogeneous due to the surroundings such as tourist spots, hydrodynamic conditions, and proximity to urban areas, plastic industries and due to recharge by the highly contaminated tributaries. The MPs identified on the basis of size dimensions show that S1 (0.5-1 mm) in all matrices was highest while S2 (1-5 mm) was the lowest. Primary source MPs identified were fibers, films, fragments and foams particles while secondary sources were pellets. Results of ATR-FTIR showed that PE was the most common plastic type identified in all samples followed by PVC, PET, PP and PS. This is the first study exploring the MPs' occurrence, numeric and mass abundance and spatial distribution in the SR ecosystem. The present study may be a valuable reference for better understanding the MPs' pollution in Pakistan. The findings of the present study can help to identify the potential sources (i.e., primary and secondary) of MPs to improve waste management in the Swat District and model the transport fluxes of these microplastics in other rivers using water quality parameters and basin characteristics.

Bionomics of the unexplored sand flies fauna of District Mohmand, Khyber Pakhtunkhwa, Pakistan: assessing risk factors associated with cutaneous leishmaniasis.

BACKGROUND: Sand flies are of considerable public health importance in Pakistan because these insects are vectors of leishmaniasis. The current study explores the bionomics of sand flies, their spatial distribution pattern and cutaneous leishmaniasis-associated risk factors in District Mohmand, Khyber Pakhtunkhwa, Pakistan. METHODS: Sand flies were collected from indoor and outdoor habitats in 69 villages of five tehsils in Mohmand during July-October 2019. Risk factor data were recorded for 829 households in 94 villages. RESULTS: In total, 2065 sand flies were captured. Phlebotomus (Paraphlebotbmus) sergenti was the most abundant species. Relative density for P. sergenti and Phlebotomus papatasi was highest in Prang Ghar and lowest in Safi. Sand flies abundance peaked in August and September, corresponding to maximum relative humidity, temperature and rainfall. Relative density for P. sergenti and P. papatasi was highest in combined dwellings (indoor) and cattle corrals (outdoor). Phlebotomus sergenti and P. papatasi were abundant at an elevation of 283-1140 m on agricultural land and rangelands. Both species were recorded abundantly on Carbontites, Mesozoic and Indus suture Melange rock formations. Presence of domestic animals, ownership of pet dogs, presence of muddy dunes in the village, knowledge of sandflies and use of mosquitoes spray remained significant risk factors. CONCLUSIONS: The study reports sand fly bionomics in District Mohmand. Risk identified for cutaneous leishmaniasis are significant in strategising control methods for Health authorities can allocate localized control means to high-risk areas using these findings.

Elucidation of Mechanisms in Cu (II) Caused Hypercontraction of Rat Tracheal Rings.

Airway smooth muscle contraction is one of the primary factors involved in the initiation and progression of asthma which in turn is regulated by increased cytosolic Ca2+ concentration from intracellular stores and through transmembrane ion channels. Calcium-independent factors such as reactive oxygen species (ROS) generation, nitric oxide (NO) depletion and cyclooxygenase (COX) pathways also contribute to tracheal smooth muscle contraction. Studies on copper toxicity suggest significance of this essential micronutrient overdose in acute respiratory disorders, allergic asthma and ciliary motion in tracheal explants. However, the mechanism of copper caused hypercontraction upon direct exposure to tracheal smooth muscle is largely unknown. In this study we investigate the effect of copper exposure on isolated tracheal rings and relative contributions of various factors in acetylcholine-induced contractions. Results obtained suggest that rise in intracellular calcium concentration via voltage-operated Ca2+ channel (VOCC), store-operated Ca2+ channel (SOCC), stretch-activated channels (SAC) and TRP channel (transient receptor potential channel) activation is the major factor in copper-mediated hypercontraction. ROS generation or COX-dependent pathways do not appear to significantly contribute to Cu2+ caused hypercontraction.

Target-based drug repurposing against Candida albicans-A computational modeling, docking, and molecular dynamic simulations study.

The emergence of multidrug-resistant strains of Candida albicans has become a global threat mostly due to co-infection with immune-compromised patients leading to invasive candidiasis. The life-threatening form of the disease can be managed quickly and effectively by drug repurposing. Thus, the study used in silico approaches to evaluate Food and Drug Administration (FDA) approved drugs against three drug targets-TRR1, TOM40, and YHB1. The tertiary structures of three drug targets were modeled, refined, and evaluated for their structural integrity based on PROCHECK, ERRAT, and PROSA. High-throughput virtual screening of FDA-approved drugs (8815), interaction analysis, and energy profiles had revealed that DB01102 (Arbutamine), DB01611 (Hydroxychloroquine), and DB09319 (Carindacillin) exhibited better binding affinity with TRR1, TOM40, and YHB1, respectively. Notably, the molecular dynamic simulation explored that Gln45, Thr119, and Asp288 of TRR1; Thr107 and Ser121 of TOM40; Arg193, Glu213, and Ser228 of YHB1 are crucial residues for stable drug-target interaction. Additionally, it also prioritized Arbutamine-TRR1 as the best drug-target complex based on MM-PBSA (-52.72 kcal/mol), RMSD (2.43 Å), and radius of gyration (-21.49 Å) analysis. In-depth, PCA results supported the findings of molecular dynamic simulations. Interestingly, the conserved region (>70%) among the TRR1 sequences from pathogenic Candida species indicated the effectiveness of Arbutamine against multiple species of Candida as well. Thus, the study dispenses new insight and enriches the understanding of developing an advanced technique to consider potential antifungals against C. albicans. Nonetheless, a detailed experimental validation is needed to investigate the efficacy of Arbutamin against life-threatening candidiasis.

Cytidine deamination-induced perpetual immunity to SAR-CoV-2 infection is a potential new therapeutic target.

As the world is racing to develop perpetual immunity to the SARS-CoV-2 virus. The emergence of new viral strains, together with vaccination and reinfections, are all contributing to a long-term immunity against the deadly virus that has taken over the world since its introduction to humans in late December 2019. The discovery that more than 95 percent of people who recovered from COVID-19 had long-lasting immunity and that asymptomatic people have a different immune response to SARS-CoV-2 than symptomatic people has shifted attention to how our immune system initiates such diverse responses. These findings have provided reason to believe that SARS-CoV-2 days are numbered. Hundreds of research papers have been published on the causes of long-lasting immune responses and variations in the numbers of different immune cell types in COVID 19 survivors, but the main reason of these differences has still not been adequately identified. In this article, we focus on the activation-induced cytidine deaminase (AID), which initiates molecular processes that allow our immune system to generate antibodies against SARS-CoV-2. To establish lasting immunity to SARS-CoV-2, we suggest that AID could be the key to unlocking it.

A systematic review on distribution and antifungal resistance pattern of Candida species in the Indian population.

The emergence of antifungal drug resistance in Candida species has led to increased morbidity and mortality in immunocompromised patients. Understanding species distribution and antifungal drug resistance patterns is an essential step for novel drug development. A systematic review was performed addressing this challenge in India with keywords inclusive of 'Candida', 'Antifungal Drug Resistance', 'Candidemia', 'Candidiasis' and 'India'. A total of 106 studies (January 1978-March 2020) from 20 Indian states were included. Of over 11,429 isolates, Candida albicans was the major species accounting for 37.95% of total isolates followed by C. tropicalis (29.40%), C. glabrata (11.68%) and C. parapsilosis (8.36%). Rates of antifungal resistance were highest in non-albicans Candida (NAC) species - C. haemuloni (47.16%), C. krusei (28.99%), C. lipolytica (28.89%) and C. glabrata (20.69%). Approximately 10.34% isolates of C. albicans were observed to be drug resistant. Candida species were frequently resistant to certain azoles (ketoconazole-22.2%, miconazole-22.1% and fluconazole-21.8%). In conclusion, the present systematic review illustrates the overall distribution and antifungal resistance pattern of Candida species among the Indian population that could be helpful in the future for the formation of treatment recommendations for the region but also elsewhere. LAY SUMMARY: A total of 106 studies were reviewed to define the prevalence, distribution and antifungal resistance pattern of Candida species in India. The presented data could become the point of reference for all reported findings on Candida species in India.