Adenosine A2AR in viral immune evasion and therapy: unveiling new avenues for treating COVID-19 and AIDS.

Adenosine is a neuro- and immunomodulator that functions via G protein-coupled cell surface receptors. Several microbes, including viruses, use the adenosine signaling pathway to escape from host defense systems. Since the recent research developments in its role in health and disease, adenosine and its signaling pathway have attracted attention for targeting to treat many diseases. The therapeutic role of adenosine has been extensively studied for neurological, cardiovascular, and inflammatory disorders and bacterial pathophysiology, but published data on the role of adenosine in viral infections are lacking. Therefore, the purpose of this review article was to explain in detail the therapeutic role of adenosine signaling against viral infections, particularly COVID-19 and HIV. Several therapeutic approaches targeting A2AR-mediated pathways are in development and have shown encouraging results in decreasing the intensity of inflammatory reaction. The hypoxia-adenosinergic mechanism provides protection from inflammation-mediated tissue injury during COVID-19. A2AR expression increased remarkably in CD39 + and CD8 + T cells harvested from HIV patients in comparison to healthy subjects. A combined in vitro treatment performed by blocking PD-1 and CD39/adenosine signaling produced a synergistic outcome in restoring the CD8 + T cells funstion in HIV patients. We suggest that A2AR is an ideal target for pharmacological interventions against viral infections because it reduces inflammation, prevents disease progression, and ultimately improves patient survival.

The Rising Tide of Antibiotic Resistance: A Study on Extended-Spectrum Beta-Lactamase and Carbapenem-Resistant Escherichia coli and Klebsiella pneumoniae.

BACKGROUND: The global spread of extended-spectrum beta-lactamase (ESBL)-producing and carbapenem-resistant Enterobacterales (CRE) poses a significant concern. Acquisition of antimicrobial resistance genes leads to resistance against several antibiotics, limiting treatment options. We aimed to study ESBL-producing and CRE transmission in clinical settings. METHODS: From clinical samples, 227 ESBL-producing and CRE isolates were obtained. The isolates were cultured on bacterial media and confirmed by VITEK 2. Antibiograms were tested against several antibiotics using VITEK 2. The acquired resistance genes were identified by PCR. RESULTS: Of the 227 clinical isolates, 145 (63.8%) were Klebsiella pneumoniae and 82 (36.1%) were Escherichia coli; 76 (33.4%) isolates were detected in urine, 57 (25.1%) in pus swabs, and 53 (23.3%) in blood samples. A total of 58 (70.7%) ESBL-producing E. coli were resistant to beta-lactams, except for carbapenems, and 17.2% were amikacin-resistant; 29.2% of E. coli isolates were resistant to carbapenems. A total of 106 (73.1%) ESBL-producing K. pneumoniae were resistant to all beta-lactams, except for carbapenems, and 66.9% to ciprofloxacin; 38 (26.2%) K. pneumoniae were resistant to carbapenems. Colistin emerged as the most effective antibiotic against both bacterial types. Twelve (20.6%) E. coli isolates were positive for blaCTX-M, 11 (18.9%) for blaTEM, and 8 (33.3%) for blaNDM. Forty-six (52.3%) K. pneumoniae isolates had blaCTX-M, 27 (18.6%) blaTEM, and 26 (68.4%) blaNDM. CONCLUSION: This study found a high prevalence of drug-resistant ESBL-producing and CRE, highlighting the need for targeted antibiotic use to combat resistance.

Clinical utility of oesophageal temperature monitoring in AF ablation: An updated meta-analysis and review of literature.

BACKGROUND: Atrial fibrillation (AF) ablation can lead to oesophageal thermal injuries (ETI). These are thought to be the precursor of the much rarer but frequently fatal atrio-oesophageal fistulas. Many centers performing AF ablation routinely use oesophageal temperature monitoring (ETM). This meta-analysis aims to determine the utility of ETM in preventing ETI in the context of radiofrequency catheter ablation of AF. METHODS: A systematic search of PubMed, Embase databases and Cochrane registry was performed comparing ETI between ETM and non-ETM strategies in AF ablation. Data on endoscopically determined ETI, AF recurrence, procedure time and ablation time were extracted. Statistical analyses including subgroup and covariate analyses were performed using random effect model in R platform. RESULTS: ETI were similar in both ETM (n = 864) and non- ETM groups (n = 639) (RR 1.04, 95 % CI 0.34-3.23) across 12 studies. AF recurrence was statistically similar in both groups (IRR 0.92, 95 % CI 0.73-1.17) but showed a lower trend in non-ETM group. Ablation time was numerically lower in the ETM group and procedure time was numerically higher trend in the ETM group; but they were not statistically significant. Covariate analysis found that posterior wall ablation power setting, additional linear ablation, BMI, use of GA or prophylactic PPI after ablation had no significant correlation in the incidence of ETI. CONCLUSION: ETM was not associated with a reduced incidence of ETI during AF ablation. Evidence supporting the routine use of ETM to reduce the risk of ETI or atrio-oesophageal fistulas is lacking.

Role of gibberellins, neem leaf extract, and serine in improving wheat growth and grain yield under drought-triggered oxidative stress.

The foliar application of gibberellins (GA3), neem leaf extract (NLE) and serine can be proven as effective growth regulating agents to counter drought stress-related deleterious effects. The literature about the collaborative role of these substances in foliar spray application under drought stress is not available to this date. No single report is available in literature on combine foliar application of GA3, NLE, and serine in improving wheat growth and yield under drought-triggered oxidative stress. The objective of this study was to induct tolerance against drought stress in order to sustain maximum growth and yield of wheat varieties (Anaj-2017 and Galaxy-2013) with foliar applications of GA3, NLE, and serine. The current field trial was designed to disclose the protective role of these substances in wheat varieties (Anaj-2017 and Galaxy-2013) under water-deficit stress. Two irrigation levels, i.e., control (normal irrigation) and water stress (water deficit irrigation), and 5 levels of GA3, NLE and serine i.e., control (water spray), GA3 (10.0 ppm), NLE (10.0%), serine (9.5 mM), and mixture (GA3 + NLE + serine) in a 1:1:1 ratio was applied. Application of these substances improved the pigments (Chlorophyll a, b), carotenoids, growth, biomass, and grain yield traits of both wheat varieties under water-deficit stress. Activities of antioxidant enzymes (POD, CAT and SOD), and non-enzymatic antioxidants (proline, total phenolic contents, anthocyanin and free amino acids) were up-regulated under drought stress and with foliar spray treatments. The foliar applications of these substances reduced the drought triggered overproduction of lipid peroxidation (MDA) and H2O2. The study found that Galaxy-2013 variety is more tolerant to drought stress than Anaj-2017, while co-applied treatments (GA3 + NLE + serine) were shown to be the most effective among all applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s12298-023-01402-9.

An exploratory study to identify the factors influencing community pharmacist retention by using COM-B model.

BACKGROUND: Due to multitude of gaps in Pakistan's healthcare system, community pharmacies serve as the" first port of call" for various illnesses. However, the present scarcity of pharmacists in these settings poses significant challenges to healthcare delivery in the country. This scarcity is primarily due to difficulties in retaining pharmacists for community practice. The aim of this study was to explore the factors that influence the retention of community pharmacists by using COM-B model. METHODS: A qualitative methodology employing the COM-|B model was utilized to design this study. In-depth interviews were conducted with pharmacists experienced in community pharmacy practice, at time and place convenient to them. Data were transcribed, translated and analyzed by deductive thematic analysis in accordance with the constructs of COM-B model. RESULTS: A diverse range of factors were identified that negatively influenced the retention of community pharmacists including working conditions and proprietor's demeanor, deficiency in training and intern experience, lack of career planning, low social acceptance, less salary and job satisfaction, less regulatory control and aptitude of renting out category. Conversely, the study also identified the factors that motivate community pharmacists to stay in their roles despite the challenges including strong educational background, abundant job opportunities, flexible schedules, direct patient engagement and positive impact on sales. CONCLUSION: There was an observed discrepancy between the challenges faced by community pharmacists and the motivators that encourage them to continue their job. Due to a disparity and abundance of challenges rather than motivators, retention rates for community pharmacists are low. This imbalance shed light on areas where improvements are needed to enhance pharmacist retention. Various areas for change were highlighted including strict implementation of regulations, integration of practical experience of community pharmacy practice and internships into academic programs, career guidance, and raising patient awareness about the roles of community pharmacists.

The least sample size essential for detecting changes in clustering solutions of streaming datasets.

The clustering analysis approach treats multivariate data tuples as objects and groups them into clusters based on their similarities or dissimilarities within the dataset. However, in modern world, a significant volume of data is continuously generated from diverse sources over time. In these dynamic scenarios, the data is not static but continually evolves. Consequently, the interesting patterns and inherent subgroups within the datasets also change and develop over time. The researchers have paid special attention to monitoring changes in cluster solutions of evolving streams. For this matter, several algorithms have been proposed in the literature. However, to date, no study has examined the effect of variability in cluster sizes on the evolution of cluster solutions. Moreover, no guidance is available on determining the impact of cluster sizes on the type of changes they experience in the streams. In the present simulation study using artificial datasets, the evolution of clusters is examined concerning the variability in cluster sizes. The findings are substantial because tracing and monitoring the changes in clustering solutions have a wide range of applications in every field of research. This study determines the minimum sample size required in the clustering of time-stamped datasets.

Unraveling the contribution of copper seed priming in enhancing chromium tolerance in wheat by improving germination, growth, and grain yield.

Exposure to chromium (Cr) on farmlands drastically restricts the growth and productivity of cereal crops, including wheat (Triticum aestivum L.). Utilizing micronutrients, the seed-priming strategy is crucial to preventing the adverse consequences of Cr-stress. Nevertheless, additional investigation needs to be conducted to figure out whether Cu-priming remedies are beneficial for wheat experiencing Cr-stress. The objective of this study was to ascertain the contribution of Cu-treated seed priming in the mitigation of detrimental impacts of Cr-stress on wheat germination, growth, and production. Two wheat cultivars, Dilkash-20 and Subhani-21, were subjected to seed priming treatments (0 mg/L, 0.1 mg/L, and 1.0 mg/L) of Cu under Cr-stress levels (200 mg/kg) in two successive experiments, respectively, petri-dish and soil-filled pot experiments. The Cu-priming significantly enhanced the wheat seed germination, plant growth, and grain yield under Cr-stress. Cu priming improved enzyme activities such as glutathione peroxidase (14.60, 16.30%), superoxide dismutase (62.55, 115.21%), peroxidase, catalase (78.39, 80.23%), ascorbate peroxidase(17.72, 20.32%), and key primary and secondary metabolites such as proline (54.19, 81.27%), glycine betaine (40.13, 79.39%), total soluble proteins (47.92, 51.58%), phenolics (40.05, 18.61%), and flavonoids (56.90, 113.46%), respectively, of Dilkash-20 and Subhani-21 under Cr-stress. The outcome of our investigation underscored the efficacy of Cu-priming treatments (0.1 mg/L and 1.0 mg/L) in Cr-stress circumstances to augment wheat germination, growth, and grain yield.

Variability in Reproductive Choices: A Comprehensive Analysis of Women's Working Status and Fertility Behavior in Pakistan.

The relationship between women's working status and fertility behavior has been a topic of interest for researchers and policymakers. The societal shifts over time, particularly the increasing participation of women in the workforce, have transformed traditional roles. Women, once primarily perceived as caregivers, are now assuming roles of economic independence. This transformation prompts a re-evaluation of the traditional association between women's working status and fertility behavior. This study aims to investigate the impact of women's working status on fertility behavior using a multistage stratified sampling design. A total of 408 women aged 15 to 49 years were recruited from 2 strata: working and non-working women. The data were collected through face-to-face interviews using a structured questionnaire. Descriptive statistics, cluster analysis, and generalized additive models were used for in-depth analysis of the dataset. An examination of fertility patterns indicates that, on average, working women bear 2.90 live children, while their non-working counterparts have an average of 3.52 children. Stillbirth was reported in 13% of housewives and 15.1% of working women. However, further analysis revealed that the relationship between women's employment status and fertility behavior varied depending on Social and Cultural Norms, Reproductive Rights, Workplace Policies, Economic Independence, Age, and Life Stage. Our findings suggest that promoting access to family-friendly policies and services, as well as challenging gender norms and cultural values, could help address the impact of women's employment on fertility behavior.

Frequency, management and impact of adverse events on treatment outcomes in patients with multidrug resistant tuberculosis in Balochistan, Pakistan.

Background: Early detection, monitoring, and managing adverse events (AEs) are crucial in optimising treatment for multidrug-resistant tuberculosis (MDR-TB) patients. Objectives: To investigate the incidence, factors, management, and impact of AEs on treatment outcomes in MDR-TB patients. Methods: This study reviewed the medical records of 275 MDR-TB patients at Fatimah Jinnah Institute of Chest Diseases in Quetta, Pakistan. Patient information was collected using a designed data collection form. Mann-Whitney U and Kruskal-Wallis tests examined the difference in AEs occurrences based on patients' characteristics. Multiple binary logistic regression identified factors associated with unsuccessful outcomes, with statistical significance set at a p-value < 0.05. Results: Almost all patients (99.6%) experienced at-least one AE (median = 4/patient, interquartile range:3-6). The most common were GI disturbance (95.3%), arthralgia (80.4%), body pain and headache (61.8%), ototoxicity (61.4%), psychiatric disturbance (44%), hypokalaemia (40.4%), dermatological reactions (26.2%) and hypothyroidism (21.5%). AEs led to treatment modification in 7.3% patients. Educated patients, those with a history of TB treatment, previous use and resistance to any second-line drug had significantly higher number of AEs. A total of 64.0% were declared cured, 3.6% completed treatment, 19.6% died and 12.7.9% were lost to follow-up. Patients' age of 41-60(OR = 9.225) and >60 years(OR = 23.481), baseline body weight of 31-60 kg(OR = 0.180), urban residence(OR = 0.296), and experiencing ototoxicity (OR = 0.258) and hypothyroidism (OR = 0.136) were significantly associated with unsuccessful treatment outcomes. Conclusion: AEs were highly prevalent but did not negatively impact treatment outcomes. Patients at higher risk of developing AEs and unsuccessful outcomes should receive special attention for its early management.

Novel 2D MXene Cobalt Ferrite (CoF@Ti3C2) Composite: A Promising Photothermal Anticancer In Vitro Study.

In search of materials with superior capability of light-to-heat (photothermal) conversion, biocompatibility, and confinement of active photothermal materials within the cells, novel magnetic MXene-based nanocomposites are found to possess all of these criteria. The CoF@Ti3C2 composite is fabricated by a simple two-step method, including an exfoliation strategy followed by sonochemical method. MXene composite has been modified with polyvinylpyrrolidone (PVP) to improve the stability in physiological conditions. The synthesized composite was characterized with multiple analytical tools. In vitro photothermal conversion efficiency of composite was determined by the time constant method and achieved η = 34.2% with an NIR 808 nm laser. In vitro, cytotoxicity studies conducted on human malignant melanoma (Ht144) and cells validated the photothermal property of the CoF@Ti3C2-PVP composite in the presence of an NIR laser (808 nm, 1.0 W cm-2), with significantly increased cytotoxicity. Calculated IC50 values were 86 µg/mL with laser, compared to 226 µg/mL without the presence of NIR laser. Microscopic results demonstrated increased apoptosis in the presence of NIR laser. Additionally, hemolysis assay confirmed biocompatibility of CoF@Ti3C2-PVP composite for intravenous applications at the IC50 concentration. The research described in this work expands the potential applications of MXene-based nanoplatforms in the biomedical field, particularly in photothermal therapy (PTT). Furthermore, the addition of cobalt ferrite serves as a magnetic nanocomposite, which eventually helps to confine therapeutic photothermal materials inside the cells, provides enhanced photothermal conversion efficiency, and creates externally controlled theranostic nanoplatforms for cancer therapy.

Evolution of waterborne diseases: A case study of Khyber Pakhtunkhwa, Pakistan.

Objectives: In Pakistan, the degradation of drinking water quality is exacerbated by the increasing population size and rapid industrialization. Contaminated water serves as the predominant source of numerous diseases, including diarrhea, gastroenteritis, and typhoid. This article explores the evolution of waterborne diseases across 21 districts of the Khyber Pakhtunkhwa province in Pakistan by monitoring changes in the clustering solutions. Methods: The data employed in this study were sourced from 21 districts of KP by the Director-General Health Services. Cluster analysis was utilized to uncover patterns in waterborne disease incidence, while principal component analysis was employed to reveal underlying patterns and reduce dimensionality. Additionally, the MONItoring Clusters (MONIC) framework was applied for change detection, facilitating the identification of significant shifts in disease patterns over time and aiding in the understanding of temporal dynamics. Results: Our analysis indicates that two clusters survived consistently over time, while other clusters exhibited inconsistency. Profiling of the surviving clusters (C12 → C24 → C32 → C43) suggests a gradual increase in cases of bloody diarrhea in the Swat Valley, Hangu, Karak, and Lakki Marwat regions. Similarly, profiling of the surviving clusters (⊙→ C22 → C34 → C44) suggests an increase in the acute watery diarrhea (non-cholera) and typhoid fever in the regions of Peshawar, Nowshera, and Swabi. Conclusion: The findings of this study hold significant importance as they pinpoint the most vulnerable regions for various waterborne diseases. These insights offer valuable guidance to policymakers and health officials, empowering them to implement effective measures for controlling waterborne diseases in the respective regions of Khyber Pakhtunkhwa, Pakistan.