Low temperature and high humidity affect dynamics of chlorophyll biosynthesis and secondary metabolites in Cucumber.

BACKGROUND: During the cold season, low temperature (LT) and high relative humidity (HRH) are significant environmental factors in greenhouses and plastic tunnels, often hindering plant growth and development. The chlorophyll (Chl) biosynthesis inhibitory mechanisms under LT and HRH stress are still widely unclear. To understand how cucumbers seedlings respond to LT and HRH stress, we investigated the impact of these stressors on Chl biosynthesis. RESULTS: Our results revealed that individual LT, HRH and combined LT + HRH stress conditions affected chlorophyll a, b, total chlorophyll and carotenoid content, reducing the levels of these pigments. The levels of Chlorophyll precursors were also markedly reduced under LT and HRH stresses, with the greatest reduction observed in cucumber seedlings exposed to LT + HRH conditions (9/5℃, 95%HRH). The activities of glutamate-1-semialdehyde transaminase (GSA-AT), ALA dehydratase (ALAD), Mg-chelatase, and protochlorophyllide oxidoreductase (POR) were increased under individual LT, HRH, conditions but decreased by combination of LT + HRH stress condition. In addition, Chl biosynthesis related genes (except PBG) were upregulated by the HRH stress but were significantly downregulated under the LT + HRH stress condition in cucumber seedlings. Furthermore, the content of phenols, flavonoids and phenolic acids (cinnamic acid and caffeic acid) were significantly surged under LT + HRH treatment over the control. Histochemical observation showed higher O2- and H2O2 content in cucumber leaves during the LT and HRH stress. CONCLUSION: The results indicate that LT + HRH stress significantly impairs chlorophyll biosynthesis in cucumber seedlings by drastically reducing pigment accumulation, altering enzyme activity and gene expression. Additionally, LT + HRH stress induces oxidative damage, which further exacerbates the decline in chlorophyll content and affects overall cucumber metabolism.

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.

Synthesis, Aromatase Inhibition, Cytotoxicity and Molecular Docking Studies of New Fluorinated and Non-fluorinated Thiourea Derivatives of Desloratadine.

Aromatase inhibitors are among the most effective treatment of the breast cancer. Aromatase catalyzes estrogen biosynthesis, which is a long-term cause of breast cancer. Current study describes the synthesis, purification of 26 new fluorinated and non-fluorinated thiourea derivatives of desloratadine (5), and their aromatase inhibition activity, cytotoxicity against cancer cell line (MDA-MB-231). Compounds 7v and 7l exhibited a significant anti-aromatase activity, while compounds 7a, 7g-h, 7m and 7u were also significant active against MDA-MB-231 cell line. Furthermore, the molecular docking studies revealed that active compounds form key interactions with the crucial amino acid of aromatase active site including TRP224, LEU477, CYS437, ALA438, MET374, ARG115, ILE305, and PHE221, which are responsible for the binding interaction of aromatase. All analogues were new, except 7b and 7k and also lacked cytotoxicity BJ human fibroblasts, with the exception of 5 and 7x. This selectivity makes this series particularly interesting for further studies.

Recent Advances in the Development of Metal/Metal Oxide Nanoparticle and Antibiotic Conjugates (MNP-Antibiotics) to Address Antibiotic Resistance: Review and Perspective.

As per the World Health Organization (WHO), antimicrobial resistance (AMR) is a natural phenomenon whereby microbes develop or acquire genes that render them resistant. The rapid emergence and spread of this phenomenon can be attributed to human activity specifically, the improper and excessive use of antimicrobials for the treatment, prevention, or control of infections in humans, animals, and plants. As a result of this factor, many antibiotics have reduced effectiveness against microbes or may not work fully. Thus, there is a pressing need for the development of new antimicrobial agents in order to counteract antimicrobial resistance. Metallic nanoparticles (MNPs) are well known for their broad antimicrobial properties. Consequently, the use of MNPs with current antibiotics holds significant implications. MNPs, including silver nanoparticles (AgNPS), zinc oxide nanoparticles (ZnONPs), copper nanoparticles (CuNPs), and gold nanoparticles (AuNPs), have been extensively studied in conjunction with antibiotics. However, their mechanism of action is still not completely understood. The interaction between these MNPs and antibiotics can be either synergistic, additive, or antagonistic. The synergistic effect is crucial as it represents the desired outcome that researchers aim for and can be advantageous for the advancement of new antimicrobial agents. This article provides a concise and academic description of the recent advancements in MNP and antibiotic conjugates, including their mechanism of action. It also highlights their possible use in the biomedical field and major challenges associated with the use of MNP-antibiotic conjugates in clinical practice.

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.

The impact of partner's behaviour on pregnancy related outcomes and safe child-birth in Pakistan.

BACKGROUND: Pakistan is one of the nations with the worst statistics for pregnancy-related outcomes. Health programmes in underdeveloped nations frequently ignore the role of partners in maternal health, which is a crucial contributing factor in these worst situations. This research study aims to explore the role of husbands in maternity care and safe childbirth in Pakistan. METHODS: The data for this study comes from the Pakistan Maternal Mortality Survey 2019. The k-Modes clustering algorithm was implemented to generate clusters from the dataset. Cluster profiling was used to identify the problems in pregnancy-related outcomes in cases where women live away from their partners. The chi-square test and logistic regression model were fitted to identify the significant factors associated with women's health and safe childbirth. RESULTS: The finding of the study reveals that the partner's support during and after pregnancy plays a vital role in maternal health and safe child-birth. It was revealed that the women living away from their partners have certain health problems during pregnancy. These problems include Vaginal bleeding, Excessive vomiting, Chest pain, Cough, High B.P, Excessive weight gain, Body aches, Swelling of feet, and Swelling of the face. This also leads to complications and health problems in the postpartum period. Due to a lack of antenatal care from the spouse during pregnancy, the women who lived away from their partners lost their pregnancies. CONCLUSION: The study concludes that the husband's emotional and financial support substantially impacts the overall health of expecting mothers and the safety of delivery in Pakistan. Given its potential advantages for mother and child health outcomes, male engagement in health education must be acknowledged and addressed. The finding of the study is of immense importance, as it guides the policymakers to arrange various awareness programs for the male partners to support their pregnant spouse and provide proper antenatal care.

Pattern, frequency and factors associated with inappropriate high dosing in chronic kidney disease patients at a tertiary care hospital in Pakistan.

BACKGROUND: Patients with chronic kidney diseases (CKD) are susceptible to the toxic drug effects if given unadjusted doses. Although Pakistan harbors a high burden of CKD patients, there is limited information available on the frequency, pattern and factors associated with unadjusted drug doses among CKD patients. METHODS: This cross-sectional study conducted at Sandeman Provincial Hospital, Quetta included 303 non-dialysis ambulatory CKD patients (glomerular filtration rate < 60 ml/min/1.73m2). The patients' data were collected through a purpose designed data collection form. The appropriateness of doses was checked against the renal drug handbook-2018, Kidney Disease Improving Global Outcomes guidelines, British National Formulary-2022, and manufacturer leaflets. Data were analysed by SPSS 23 and multiple binary logistic regression analysis was used to assess the factors associated with receiving inappropriate high doses. A p-value < 0.05 was considered statistically significant. RESULTS: The patients received a total of 2265 prescription lines, with a median of eight different drugs per patient (interquartile range: 6-9 drugs). A total of 34.5% (783/2265) drugs required dose adjustment. Of these, doses were not adjusted for 56.1% (440) drugs in 162 (53.4%) patients. The most common pharmacological class of drugs requiring dose adjustment were antibiotics (79.1%), followed by antidiabetics (59.2%), diuretics (57.0%), angiotensin converting enzyme inhibitors (56.9%), beta blockers (56.9%), analgesics (56.0%), angiotensin receptor blockers (55.2%), domperidone (53.9%) and antihyperlipidmics (46.1%). Patient's age of 41-60 (OR = 5.76) and > 60 years (OR = 9.49), hypertension (OR = 2.68), diabetes mellitus (OR = 3.47) and cardiovascular diseases (OR = 2.82) had statistically significant association (p-value < 0.05) with inappropriate high doses. CONCLUSION: The high frequency of inappropriate high doses suggests an important quality gap in medication dosing for patients with ND-CKD at the study site. Special attention should be paid to the drugs and patients with identified risk factors for receiving inappropriate high doses.

Physical Characteristics, Blue-Green Band Emission and Photocatalytic Activity of Au-Decorated ZnO Quantum Dots-Based Thick Films Prepared Using the Doctor Blade Technique.

Nanoscale ZnO is a vital semiconductor material whose versatility can be enhanced by sensitizing it with metals, especially noble metals, such as gold (Au). ZnO quantum dots were prepared via a simple co-precipitation technique using 2-methoxy ethanol as the solvent and KOH as the pH regulator for hydrolysis. The synthesized ZnO quantum dots were deposited onto glass slides using a simple doctor blade technique. Subsequently, the films were decorated with gold nanoparticles of different sizes using a drop-casting method. The resultant films were characterized via various strategies to obtain structural, optical, morphological, and particle size information. The X-ray diffraction (XRD) reveals the formation of the hexagonal crystal structure of ZnO. Upon Au nanoparticles loading, peaks due to gold are also observed. The optical properties study shows a slight change in the band gap due to Au loading. Nanoscale sizes of particles have been confirmed through electron microscope studies. P.L. studies display blue and blue-green band emissions. The significant degradation efficiency of 90.2% methylene blue (M.B.) was attained in natural pH in 120 min using pure ZnO catalyst while one drop gold-loaded catalysts, ZnO: Au 5 nm, ZnO: Au 7 nm, ZnO: Au 10 nm and ZnO: Au 15 nm, delivered M.B. degradation efficiency of 74.5% (in 245 min), 63.8% (240 min), 49.6% (240 min) and 34.0% (170 min) in natural pH, respectively. Such films can be helpful in conventional catalysis, photocatalysis, gas sensing, biosensing, and photoactive applications.

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.

Treg cell therapy: How cell heterogeneity can make the difference.

CD4+ CD25high CD127low/- FOXP3+ T regulatory cells are responsible for maintaining immune tolerance and controlling excessive immune responses. Treg cell use in pre-clinical animal models showed the huge therapeutic potential of these cells in immune-mediated diseases and laid the foundations for their applications in therapy in humans. Currently, there are several clinical trials utilizing the adoptive transfer of Treg cells to reduce the morbidity in autoimmune disorders, allogeneic HSC transplantation, and solid organ transplantation. However, a large part of them utilizes total Treg cells without distinction of their biological variability. Many studies on the heterogeneity of Treg cell population revealed distinct subsets with different functions in the control of the immune response and induction of peripheral tolerance. Some of these subsets also showed a role in controlling the general homeostasis of non-lymphoid tissues. All these Treg cell subsets and their peculiar properties can be therefore exploited to develop novel therapeutic approaches. This review describes these functionally distinct subsets, their phenotype, homing properties and functions in lymphoid and non-lymphoid tissues. In addition, we also discuss the limitations in using Treg cells as a cellular therapy and the strategies to enhance their efficacy.

Induce defense response of DADS in eggplants during the biotrophic phase of Verticillium dahliae.

PURPOSE: Verticillium wilt is a destructive vascular disease in eggplants. The complex defensive mechanisms of eggplant against this disease are very limited. METHODS: Our work examined the bioactive properties of garlic allelochemical diallyl disulfide (DADS) as potential biostimulants for defense against V. dahliae in eggplant seedlings. We, therefore, foliar sprayed DADS on eggplants to study the defense response during the early biotrophic phase of V. dahliae (a hemibiotroph). RESULTS: DADS application significantly increased root peroxidase (POD), phenylalanine-ammonia lyase (PAL) enzyme activity, and reduced H2O2 levels after 24 h of fungal inoculation. Salicylic acid (SA) in leaves and roots was significantly increased while, the jasmonic acid (JA), indole acetic acid (IAA), and abscisic acid (ABA) levels were decreased. The microscopic examinations of V. dahliae infection in roots displayed that the progression of infection was restricted in DADS-treated plants. Depositions of lignin and phenolic compounds such as ferulic acid, p-coumaric acid, and caffeic acid content were significantly higher in DADS-treated plants at 48 h post-inoculation. Similarly, the DADS application up-regulated pathogenesis-related (PR1, PR2, and PR5), mitogen-activated protein kinase (MPK1), and lipoxygenase (LOX) genes. Furthermore, DADS-treated plants exhibited a lower disease severity index (23.3% vs. 57.0% in controls), indicating successful defense against V. dahliae. CONCLUSIONS: Our findings concluded that the biological function of garlic allelochemical DADS has a prominent role in the higher defense resistance of eggplants during the early infection of V. dahliae.

Prognostic accuracy of time to sputum culture conversion in predicting cure in extensively drug-resistant tuberculosis patients: a multicentre retrospective observational study.

BACKGROUND: There was a lack of information about prognostic accuracy of time to sputum culture conversion (SCC) in forecasting cure among extensively drug-resistant tuberculosis (XDR-TB) patients. Therefore, this study evaluated the prognostic accuracy of SCC at various time points in forecasting cure among XDR-TB patients. METHODS: This retrospective observational study included 355 eligible pulmonary XDR-TB patients treated at 27 centers in Pakistan between 01-05-2010 and 30-06-2017. The baseline and follow-up information of patients from treatment initiation until the end of treatment were retrieved from electronic nominal recording and reporting system. Time to SCC was analyzed by Kaplan-Meier method, and differences between groups were compared through log-rank test. Predictors of time to SCC and cure were respectively evaluated by multivariate Cox proportional hazards and binary logistic regression analyses. A p-value < 0.05 was considered statistically significant. RESULTS: A total of 226 (63.6%) and 146 (41.1%) patients respectively achieved SCC and cure. Median time to SCC was significantly shorter in patients who achieved cure, 3 months (95% confidence interval [CI]: 2.47-3.53), than those who did not (median: 10 months, 95% CI: 5.24-14.76) (p-value < 0.001, Log-rank test). Patient's age > 40 years (hazards ratio [HR] = 0.632, p-value = 0.004), baseline sputum grading of scanty, + 1 (HR = 0.511, p-value = 0.002), + 2, + 3 (HR = 0.523, p-value = 0.001) and use of high dose isoniazid (HR = 0.463, p-value = 0.004) were significantly associated with early SCC. Only SCC at 6 month of treatment had statistically significant association with cure (odds ratio = 15.603, p-value < 0.001). In predicting cure, the sensitivities of SCC at 2, 4 and 6 months were respectively 41.8% (95%CI: 33.7-50.2), 69.9% (95%CI: 61.7-77.2) and 84.9% (95%CI: 78.1-90.3), specificities were respectively, 82.8% (95%CI: 76.9-87.6), 74.6% (95%CI: 68.2-80.4) and 69.4% (95%CI: 62.6-75.5) and prognostic accuracies were respectively 65.9% (95%CI: 60.7-70.8), 72.7% (95%CI: 67.7-77.2) and 75.8% (95%CI: 71.0-80.1). CONCLUSION: In forecasting cure, SCC at month 6 of treatment performed better than SCC at 2 and 4 months. However, it would be too long for clinicians to wait for 6 months to decide about the regimen efficacy. Therefore, with somewhat comparable prognostic accuracy to that SCC at 6 month, using SCC at 4 month of treatment as a prognostic marker in predicting cure among XDR-TB patients can decrease the clinicians waiting time to decide about the regimen efficacy.

Adenosine A2A receptor as a potential target for improving cancer immunotherapy.

The adenosine nucleoside performs a wide range of actions on various human tissues by activating four cell surface receptors. Adenosine A2A receptors (A2ARs) are widely expressed in the striatum, olfactory bulb, platelets, leukocytes, spleen, and thymus. They promote vasodilatation, platelet antiaggregatory effect, protection from ischemic damage, and regulation of sensorimotor neurons in basal ganglia. Adenosine signaling plays a vital part in modulating in vivo pathophysiological responses. A2ARs are potent negative regulators of the antitumor and proinflammatory actions of activated T cells. This axis offers several therapeutic targets, the most important of which are A2ARs, HIF-1α, and CD39/CD73. Downregulation of this axis increases the effectiveness of modern immunotherapeutic approaches against cancer, such as αCTLA-4/αPD-1. These discoveries have led to a promising novel role of antagonists of A2AR in blocking angiogenesis in immunotherapy of cancer. A small molecule, AZD4635, strongly inhibits A2AR, lowering cancer volume and increasing anticancer immunity. Deletion of A2AR with CRISPR/Cas9 in both human and murine CAR T cells produces a substantial increase in the efficiency of these cells. This review asserts that inhibition of the adenosinergic pathway can boost antitumor immunity, and this axis should be a target for future immunotherapeutic strategies.

Evaluation of potential drug-drug interactions in cancer patients at a tertiary care hospital in Pakistan.

BACKGROUND: Despite harboring a high burden of cancer patients who are at high risk of potential drug-drug interactions (pDDIs), there is scarcity of published information about pDDIs in cancer patients from Pakistan. OBJECTIVE: To evaluate frequency, pattern, mechanism and factors associated with pDDIs in cancer patients treated at a tertiary care hospital in Pakistan. METHODS: In this cross-sectional analytical study, a total of 253 eligible ambulatory cancer patients treated at Center for Nuclear Medicine and Radiotherapy Hospital Quetta were evaluated for pDDIs using IBM Micromedex® Drug Interactions. SPSS (version 26) was used for conducting multivariate analysis to find factors associated with the presence pDDIs. A p-value <0.05 was considered statistically significant. RESULTS: A total of 141/253 (55.7%) patients were exposed to at-least one pDDI. A total of 251 pDDIs were noted with a median of one pDDI/per patient (interquartile range:1-2) Majority interactions were of major severity (72.9%), pharmacodynamic (49.8%) and had fair documentation level (64.1%). Anti-cancer drugs were involved in 73.0% pDDIs with doxorubicin as the most commonly involved (40.0%) anti-cancer followed by cyclophosphamide (27.6%) and cisplatin (13.5%). Potential cardiac adverse events made the bulk (33.8%) of predicted events. Receiving >2 anti-cancer (OR = 5.19, p-value = 0.001) and >6 ancillary drugs (OR = 4.16, p-value = 0.033) emerged as the risk factors of pDDIs. CONCLUSIONS: The prevalence of pDDIs was within the range reported in published literature. Solid medication review, availability of DDI detecting tools and clinical pharmacist, and paying special attention to the high-risk patients may reduce the frequency of pDDIs at the study site.

Towards Enhancing Traffic Sign Recognition through Sliding Windows.

Automatic Traffic Sign Detection and Recognition (TSDR) provides drivers with critical information on traffic signs, and it constitutes an enabling condition for autonomous driving. Misclassifying even a single sign may constitute a severe hazard, which negatively impacts the environment, infrastructures, and human lives. Therefore, a reliable TSDR mechanism is essential to attain a safe circulation of road vehicles. Traffic Sign Recognition (TSR) techniques that use Machine Learning (ML) algorithms have been proposed, but no agreement on a preferred ML algorithm nor perfect classification capabilities were always achieved by any existing solutions. Consequently, our study employs ML-based classifiers to build a TSR system that analyzes a sliding window of frames sampled by sensors on a vehicle. Such TSR processes the most recent frame and past frames sampled by sensors through (i) Long Short-Term Memory (LSTM) networks and (ii) Stacking Meta-Learners, which allow for efficiently combining base-learning classification episodes into a unified and improved meta-level classification. Experimental results by using publicly available datasets show that Stacking Meta-Learners dramatically reduce misclassifications of signs and achieved perfect classification on all three considered datasets. This shows the potential of our novel approach based on sliding windows to be used as an efficient solution for TSR.

Drug resistance patterns, treatment outcomes and factors affecting unfavourable treatment outcomes among extensively drug resistant tuberculosis patients in Pakistan; a multicentre record review.

Background: Extensively drug resistant tuberculosis (XDR-TB) is considered as a major threat to global health. This study aimed to analyse the treatment outcomes and identify the factors significantly associated with unfavourable treatment outcomes among XDR-TB patients. Methods: We conducted a retrospective observational study at 10 Programmatic Management Units of the National Tuberculosis Control Program of Pakistan. The Electronic Nominal Recording Reporting System records were used to collect data of all eligible XDR-TB patients registered at the study sites between March 2012 and August 2018. Treatment outcomes were analysed as per the standard criteria. Factors associated with unfavourable treatment outcomes were analysed by using multivariate binary logistic regression analysis. Results: Out of the total 184 patients, 59 (32.1%) completed their treatment successfully. Whereby, 83 patients (45.1%) died, 24 (13%) had treatment failure, and 11 (6%) were lost to follow-up. Treatment outcomes were not evaluated in 7 (3.8%) patients. Factors significantly associated with unfavourable treatment outcomes included; conventional therapy with bedaquiline, unfavourable interim treatment outcomes and occurrence of adverse drug events (negative association). Conclusion: Treatment success rate in the study cohort was sub-optimal (i.e., <75%). The poor success rate and high mortality are concerning, and requires immediate attention of the program managers and clinicians.

Estimation of serum iron, serum lipids and serum liver enzymes in celiac disease patients of Saudi Arabia.

Objectives: To evaluate the serum biochemical levels in celiac disease (CD) patients. Methods: It was a cross-sectional study carried out on 70 subjects, including 40 patients with CD and 30 healthy controls. This study was conducted at Jouf University from November, 2020 to October, 2021. The collected blood specimens were used to perform serum iron, serum lipids, liver enzymes, and human tissue transglutaminase IgA antibodies (anti-HTTG). The hematological parameters including hematocrit and MCV were determined to establish the diagnosis of iron deficiency. Results: Serum iron was significantly lower in patients as compared to the controls. Serum iron, serum HDL, blood hematocrit and MCV were significantly lower in patients than in controls (p = 0.000). Serum levels of liver enzymes (ALT and AST) and serum human tissue transglutaminase antibodies (anti-HTTG) were significantly higher in patients than in controls (p = 0.000). The correlation studies established the negative correlation of anti-HTTG IgA with serum iron (r = -0.991, p = 0.000), hematocrit (r = -0.967, p = 0.000) and MCV (r = -0.946, p = 0.000) in patients. Conclusion: The serum iron was remarkably reduced in CD patients. A negative correlation was found between anti-HTTG IgA and serum iron, while a positive serum iron was correlated with hematocrit and MCV in CD patients.

Soil enrichment with actinomycete mitigates the toxicity of arsenic oxide nanoparticles on wheat and maize growth and metabolism.

The use of plant growth-promoting bacteria (PGPB) to enhance plant growth and protection against heavy metal toxicity has been extensively studied. However, its potentiality to reduce arsenate toxicity, a threat to plant growth and metabolism, has been hardly investigated. Moreover, the toxic effect of arsenic oxide nanoparticles (As-NPs) on plants and possible mechanisms for its alleviation has not yet been explored. In this study, the impact of the bioactive actinomycete Streptomyces spp. on the growth, physiology and stress-related metabolites, such as sugars and proline, on As-NPs-stressed wheat and maize plants was investigated. Soil amendment with arsenic oxide nanoparticles (As-NPs) induced the uptake and accumulation of As in the plants of both species, resulting in reduced growth and photosynthesis, but less marked in maize than in wheat plants. Under As-NPs-free conditions, Streptomyces spp. treatment markedly improved growth and photosynthesis in wheat only. The application of Streptomyces spp. reduced As accumulation, recovered the As-NPs-induced growth, photosynthesis inhibition, and oxidative damage in plants of both species. Wheat plants specifically accumulated soluble sugars, while both species accumulated proline. Under As-NPs stress, the ornithine pathway of proline biosynthesis was more important in maize than in wheat plants, while the glutamine pathway was dominant in wheat ones. The addition of Streptomyces spp. further induced the accumulation of proline and starch in both plant species. Overall, despite a different response to Streptomyces spp. under nontoxic conditions, the amendment of as-contaminated soil with Streptomyces spp. induced similar metabolic responses in the two tested species, which trigger stress recovery.

Selective detection of preferential activity of Lanthanum ion at zinc oxide functionalized nanochannel.

A significant increase of rare earth transition metals concentration in water reservoirs caused by the dumping of household materials and petrol-producing industries is a potential threat to human and aquatic life. Here, we demonstrate a model nanofluidic channel for the Lanthanum (La3+) ions recognition. To this end, a single conical nanochannel is first modified with poly allylamine hydrochloride followed by immobilization of synthesized ZnO nanoparticles on the channel surface through electrostatic adsorption. A significant change in the nanopore electrical readout is noticed when the functionalized nanochannel is exposed to an electrolyte solution having La3+cations. The distinctive response by the nanofluidic system towards La3+ions is assumed to be due to ionic radii, hexagonal crystal structure, and associated basal plane interaction between anchored ZnO nanoparticles and La3+ions. We anticipate that this nanofluidic system can be used as a model to design highly sensitive metal ion detection devices.