Enhanced wheat productivity in saline soil through the combined application of poultry manure and beneficial microbes.

BACKGROUND: Soil salinity is one of the major menaces to food security, particularly in dealing with the food demand of the ever-increasing global population. Production of cereal crops such as wheat is severely affected by soil salinity and improper fertilization. The present study aimed to examine the effect of selected microbes and poultry manure (PM) on seedling emergence, physiology, nutrient uptake, and growth of wheat in saline soil. A pot experiment was carried out in research area of Institute of Soil and Environmental Sciences, University of Agriculture, Faisalabad, Pakistan. Saline soil (12 dS m- 1 w/w) was developed by spiking using sodium chloride, and used in experiment along with two microbial strains (i.e., Alcaligenes faecalis MH-2 and Achromobacter denitrificans MH-6) and PM. Finally, wheat seeds (variety Akbar-2019) were sown in amended and unamended soil, and pots were placed following a completely randomized design. The wheat crop was harvested after 140 days of sowing. RESULTS: The results showed a 10-39% increase (compared to non-saline control) in agronomic, physiological, and nutritive attributes of wheat plants when augmented with PM and microbes. Microbes together with PM significantly enhanced seedling emergence (up to 38%), agronomic (up to 36%), and physiological (up to 33%) in saline soil as compared to their respective unamended control. Moreover, the co-use of microbes and PM also improved soil's physicochemical attributes and enhanced N (i.e., 21.7%-17.1%), P (i.e., 24.1-29.3%), and K (i.e., 28.7%-25.3%) availability to the plant (roots and shoots, respectively). Similarly, the co-use of amendments also lowered the Na+ contents in soil (i.e., up to 62%) as compared to unamended saline control. This is the first study reporting the effects of the co-addition of newly identified salt-tolerant bacterial strains and PM on seedling emergence, physiology, nutrient uptake, and growth of wheat in highly saline soil. CONCLUSION: Our findings suggest that co-using a multi-trait bacterial culture and PM could be an appropriate option for sustainable crop production in salt-affected soil.

Diabetic autonomic neuropathy does not impede improvement in hypoglycaemia awareness in adults: Sub-study results from the HypoCOMPaSS trial.

AIMS: Impaired awareness of hypoglycaemia (IAH) increases the risk of severe hypoglycaemia in people with type 1 diabetes mellitus (T1DM). IAH can be reversed through meticulous avoidance of hypoglycaemia. Diabetic autonomic neuropathy (DAN) has been proposed as an underlying mechanism contributing to IAH; however, data are inconsistent. The aim of this study was to examine the effects of cardiac autonomic neuropathy (CAN) on IAH reversibility inT1DM. METHODS: Participants with T1DM and IAH (Gold score ≥4) recruited to the HypoCOMPaSS (24-week 2 × 2 factorial randomised controlled) trial were included. All underwent screening for cardiac autonomic function testing at baseline and received comparable education and support aimed at avoiding hypoglycaemia and improving hypoglycaemia awareness. Definite CAN was defined as the presence of ≥2 abnormal cardiac reflex tests. Participants were grouped according to their CAN status, and changes in Gold score were compared. RESULTS: Eighty-three participants (52 women [62.7%]) were included with mean age (SD) of 48 (12) years and mean HbA1c of 66 (13) mmol/mol (8.2 [3.3] %). The mean duration of T1DM was 29 (13) years. The prevalence of CAN was low with 5/83 (6%) participants having definite autonomic neuropathy with 11 (13%) classified with possible/early neuropathy. All participants, regardless of the autonomic function status, showed a mean improvement in Gold score of ≥1 (mean improvement -1.2 [95% CI -0.8, -1.6]; p < 0.001). CONCLUSIONS: IAH can be improved in people with T1DM, and a long duration of disease, with and without cardiac autonomic dysfunction. These data suggest that CAN is not a prime driver for modulating IAH reversibility.

Recent Developments on Electroactive Organic Electrolytes for Non-Aqueous Redox Flow Batteries: Current Status, Challenges, and Prospects.

The ever-increasing threat of climate change and the depletion of fossil fuel resources necessitate the use of solar- and wind-based renewable energy sources. Large-scale energy storage technologies, such as redox flow batteries (RFBs), offer a continuous supply of energy. Depending on the nature of the electrolytes used, RFBs are broadly categorized into aqueous redox flow batteries (ARFBs) and non-aqueous redox flow batteries (NARFBs). ARFBs suffer from various problems, including low conductivity of electrolytes, inferior charge/discharge current densities, high-capacity fading, and lower energy densities. NARFBs offer a wider potential window and range of operating temperatures, faster electron transfer kinetics, and higher energy densities. In this review article, a critical analysis is provided on the design of organic electroactive molecules, their physiochemical/electrochemical properties, and various organic solvents used in NARFBs. Furthermore, various redox-active organic materials, such as metal-based coordination complexes, quinones, radicals, polymers, and miscellaneous electroactive species, explored for NARFBs during 2012-2023 are discussed. Finally, the current challenges and prospects of NARFBs are summarized.

Recent Development of Electrolytes for Aqueous Organic Redox Flow Batteries (Aorfbs): Current Status, Challenges, and Prospects.

In recent years, aqueous organic redox flow batteries (AORFBs) have attracted considerable attention due to advancements in grid-level energy storage capacity research. These batteries offer remarkable benefits, including outstanding capacity retention, excellent cell performance, high energy density, and cost-effectiveness. The organic electrolytes in AORFBs exhibit adjustable redox potentials and tunable solubilities in water. Previously, various types of organic electrolytes, such as quinones, organometallic complexes, viologens, redox-active polymers, and organic salts, were extensively investigated for their electrochemical performance and stability. This study presents an overview of recently published novel organic electrolytes for AORFBs in acidic, alkaline, and neutral environments. Furthermore, it delves into the current status, challenges, and prospects of AORFBs, highlighting different strategies to overcome these challenges, with special emphasis placed on their design, composition, functionalities, and cost. A brief techno-economic analysis of various aqueous RFBs is also outlined, considering their potential scalability and integration with renewable energy systems.

Global health inequalities of chronic kidney disease: a meta-analysis.

BACKGROUND AND HYPOTHESIS: Chronic kidney disease (CKD) is a significant contributor to global morbidity and mortality. This study investigated disparities in age, sex and socio-economic status in CKD and updated global prevalence estimates through systematic review and meta-analysis. METHODS: Five databases were searched from 2014 to 2022, with 14 871 articles screened, 119 papers included and data analysed on 29 159 948 participants. Random effects meta-analyses were conducted to determine overall prevalence, prevalence of stages 3-5 and prevalence in males/females. Influences of age, sex and socio-economic status were assessed in subgroup analyses, and risk of bias assessment and meta-regressions were conducted to explore heterogeneity. RESULTS: Overall prevalence of CKD was 13.0% (11.3-14.8%) and 6.6% (5.6-7.8%) for stages 3-5. Prevalence was higher in studies of older populations (19.3% for stages 1-5, 15.0% for stages 3-5) and meta-regression demonstrated association of age, body mass index, diabetes and hypertension with prevalence of stages 3-5. The prevalence of CKD stages 1-5 was similar in males and females (13.1% versus 13.2%) but prevalence of stages 3-5 was higher in females (6.4% versus 7.5%). Overall prevalence was 11.4%, 15.0% and 10.8% in low, middle and high-income countries respectively; for stages 3-5 prevalence was 4.0%, 6.7% and 6.8%, respectively. Included studies were at moderate-high risk of bias in the majority of cases (92%), and heterogeneity was high. CONCLUSION: This study provides a comprehensive assessment of CKD prevalence, highlighting important disparities related to age, sex and socio-economic status. Future research should focus on targeted screening and treatment approaches, improving access to care and more effective data monitoring, particularly in low or middle income countries.

Transcutaneous Delivery of Dexamethasone Sodium Phosphate Via Microneedle-Assisted Iontophoretic Enhancement - A Potential Therapeutic Option for Inflammatory Disorders.

AIM: This study aimed to fabricate dexamethasone sodium phosphate loaded microneedle arrays (MNA) and investigate their efficiency in combination with iontophoresis for the treatment of hind paw oedema in rats. METHODS: Drug loaded polyvinyl alcohol, polyvinyl pyrrolidone and D-sorbitol-based MNA11 were fabricated by vacuum micromolding. Physicochemical, morphological, thermal, in-silico, in-vitro insertion ability (on parafilm) and drug release studies were performed. Ex-vivo permeation, in-vivo insertion and anti-inflammatory studies were performed in combination with iontophoresis. RESULTS: MNA11 displayed sharp-tipped projections and acceptable physicochemical features. Differential scanning calorimetry results indicated that drug loaded MNA11 were amorphous solids. Drug interacted with PVP and PVA predominately via hydrogen bonding. Parafilm displayed conspicuously engraved complementary structure of MNA11. Within 60 min, 91.50 ± 3.1% drug released from MNA11. A significantly higher i.e., 95.06 ± 2.5% permeation of drug was observed rapidly (within 60 min) from MNA11-iontophoresis combination than MNA11 i.e., 84.07 ± 3.5% within 240 min. Rat skin treated using MNA11 and MNA11-iontophoresis showed disruptions / microchannels in the epidermis without any damage to underlying anatomical structures. MNA11-iontophoresis combination led to significant reduction (83.02 ± 3.9%) in paw oedema as compared to MNA11 alone (72.55 ± 4.1%). CONCLUSION: MNA11-iontophoresis combination can act as a promising candidate to deliver drugs transcutaneously for treating inflammatory diseases.

Design, synthesis, biological evaluation and molecular docking studies of quinoline-anthranilic acid hybrids as potent anti-inflammatory drugs.

Despite the high global prevalence, rheumatoid arthritis lacks a satisfactory treatment. Hence, the present study is undertaken to design and synthesize novel anti-inflammatory compounds. For this, quinoline and anthranilic acid, two medicinally-privileged moieties, were linked by pharmacophore hybridization, and following their computational assessments, three hybrids 5a-c were synthesized in good over all yields. The in vitro and in vivo anti-inflammatory potential of these hybrids was determined by anti-denaturation and anti-proteinase, and carrageenan-induced paw edema models. The computational studies of these hybrids revealed their drug-likeness, optimum pharmacokinetics, and less toxicity. Moreover, they demonstrated high binding affinity (-9.4 to -10.6 kcal mol-1) and suitable binding interactions for TNF-α, FLAP, and COX-II. A three-step synthetic route resulted in the hybrids 5a-c with 83-86% yield of final step. At 50 µg mL-1, the antiprotease and anti-denaturation activity of compound 5b was significantly higher than 5a and 5c. Furthermore, 5b significantly reduced the edema in the right paw of the rats that received carrageenan. The results of this study indicate the medicinal worth of the novel hybrids in treating inflammatory disorders such as rheumatoid arthritis.

Integrating DFT and machine learning for the design and optimization of sodium alginate-based hydrogel adsorbents: Efficient removal of pollutants from wastewater.

This study presents a novel approach to design and optimize a sodium alginate-based hydrogel (SAH) for efficient adsorption of the model water pollutant methylene blue (MB) dye. Utilizing density functional theory (DFT) calculations, sodium alginate-g-poly (acrylamide-co-itaconic acid) was identified with the lowest adsorption energy (Eads) for MB dye among 14 different clusters. SAHs were prepared using selected monomers and sodium alginate combinations through graft co-polymerization, and swelling studies were conducted to optimize grafting conditions. Advanced characterization techniques, including FTIR, XRD, XPS, SEM, EDS, and TGA, were employed, and the process was optimized using statistical and machine learning tools. Screening tests demonstrated that Eads serves as an effective predicting indicator for adsorption capacity (qe) and MB removal efficiency (RRMB,%), with reasonable agreement between Eads and both responses under given conditions. Process modeling and optimization revealed that 5 mg of selected SAH achieves a maximum qe of 3244 mg g-1 at 84.4% RRMB under pH 8.05, 98.8 min, and MB concentration of 383.3 mg L-1, as identified by the desirability function approach. Moreover, SAH effectively eliminated various contaminants from aqueous solutions, including sulfasalazine (SFZ) and dibenzothiophene (DBT). MB adsorption onto selected SAH was exothermic, spontaneous, and followed the pseudo-first-order and Langmuir-Freundlich isotherm models. The remarkable ability of SAH to adsorb MB is attributed to its well-designed structure predicted through DFT and optimal operational conditions achieved by AI-based parametric optimization. By integrating DFT-based computations and machine-learning tools, this study contributes to the efficient design of adsorbent materials and optimization of adsorption processes, also showcasing the potential of SAH as an efficient adsorbent for the abatement of aqueous pollution.

Temporal trends in indoor bioaerosols: implications for dental healthcare environments.

Antibiotic resistance, a significant public health hazard, is predicted to cause 10 million deaths worldwide by 2050. The study aimed to identify culturable bioaerosols in the indoor air of dental units in Lahore and assess their antibiotic resistance. Air samples were collected from 10 dental unit locations at different distances, with average concentrations of fungi and bacteria falling within intermediate ranges, per the Global Index of Microbial Contamination (GIMC/m3) index. The study found higher antibiotic-resistant strains in hospital dental units, particularly during winter. The most vigorous strain, S.aureus-NAJIH18, exhibited 70% resistance to ceftazidime. The research highlights the importance of quantifying microbial pollutants for evaluating their source and complexity. It suggests proactive mitigation techniques, such as focused cleaning and air filtration, to improve indoor air quality can mitigate the spread of antibiotic-resistant strains. These insights offer hope in combating the growing public health threat of antibiotic resistance.

Novel insights regarding the safety and efficacy of pyrethroid-coated nanoparticles against Hyalomma ticks.

Nanoparticles have been shown to inhibit major life cycle stages of ticks, indicative of the promising application of nanomaterials against hard ticks. The study thus probed into one of the alternative options to curtail Hyalomma by employing nanocomposites consisting of pyrethroids (cypermethrin and deltamethrin) coated nanoparticles of iron oxides and iron sulfides keeping alongside the evaluation of their toxicity through plant and mammalian cell lines. The nanoparticles used in this study were roughly spherical in morphology and exhibited various size dimensions upon characterization using SEM, EDX, and FTIR. The application of nanomaterials on female ovipositioning tick showed a decline up to 15% (females ovipositioned) in deltamethrin-coated FeO NPs, whereas this decline was up to 18% in Cyp-FeS NPs and up to 5% in Cyp-FeO NPs. Similarly, the larval hatching was also impacted, leading to a hatching percentage of 5% and only 1% by application of Cyp-FeS NPs and Cyp-FeO NPs, respectively. Similarly, the larval groups had LC90 of 4.1 and 4.73 mg/L for the Cyp-FeO NPs and Cyp-FeS NPs groups. The delta-FeO NPs and delta-FeS NPs demonstrated a promising effect against adult ticks, showing LC50= 3.5 mg/L, LC90= 6.7 mg/L and LC50= 3.8 mg/L, LC90= 7.9 mg/L, respectively. MTT assay revealed that the pyrethroids coupled with iron oxide nanoparticles showed the least cytotoxicity even at the highest concentration (10-1 µL) among other nanomaterials. The study thus concluded a safer spectrum of non-target effects of pyrethroids-coated nanomaterials in addition to their significant anti-tick activity.

Common variable immunodeficiency associated enteropathy: A diagnostic enigma in developing countries.

Common variable immunodeficiency (CVID) is the most prevalent primary immunodeficiency disorder with different phenotypes and aetiologies. It is characterised by hypogammaglobulinaemia, defects in specific antibody response, erroneous activation and proliferation of T cells, leading to increased risk of recurrent infections. In CVID, "Variable" refers to the heterogeneity of clinical presentations, which include recurrent infections, autoimmunity, enteropathy, and increased risk of malignancies. This wide spectrum of disease manifestations and being a diagnosis of exclusion poses a diagnostic challenge. It is pertinent to mention that CVID along with associated complications is the commonest symptomatic primary antibody deficiency but is scarcely mentioned in local literature. The main aim of presenting this case is to impress upon the importance of systematic immunological workup in cases of suspected immunodeficiency to prevent morbidity and mortality.

Integrons and multidrug resistance across phylogenetic groups of clinical isolates of Escherichia coli.

Objective: This study was aimed to investigate the multidrug resistance patterns in clinical isolates of Escherichia coli and their correlation with integrons and phylogenetic groupings. Methods: A total of 37 clinical E. coli isolates were evaluated for drug resistance patterns by disk diffusion method. Phylogenetic groupings and the presence of integrons among E. coli were determined by multiplex PCR assays. Results: Multidrug resistance was identified in 84% of the clinical isolates of E. coli with higher resistance found against cephalosporins (94.6%) and fluoroquinolones (83.8%), while lower resistance was observed against polymyxins (24.3%) and carbapenems (29.7%). Metallo-ß-lactamases were found in all carbapenem resistant isolates. The phylogenetic group B2 was the most dominant (40.5%), followed by groups A (35.1%), D (13.5%) and B1 (10.8%). Integrons were detected in 25 (67.6%) isolates and intI1, intI2, and intI3 genes were found in 62.2%, 18.9% and 10.8% of isolates respectively. Conclusion: Our results show that phylogenetic classification of E. coli is not relevant with antimicrobial resistance. However, there was strong association between the integron classes and resistance against ß-lactam and fluoroquinolones antimicrobials. Additionally, this study highlighted that the presence of integrons plays a crucial role in the development of multidrug resistance in clinical isolates of E. coli. Most significantly, this is the first report of detection of three classes of integron among clinical isolates of E. coli in Pakistan.

Immune cells are increased in normal breast tissues of BRCA1/2 mutation carriers.

PURPOSE: Breast cancer risk is elevated in pathogenic germline BRCA 1/2 mutation carriers due to compromised DNA quality control. We hypothesized that if immunosurveillance promotes tumor suppression, then normal/benign breast lobules from BRCA carriers may demonstrate higher immune cell densities. METHODS: We assessed immune cell composition in normal/benign breast lobules from age-matched women with progressively increased breast cancer risk, including (1) low risk: 19 women who donated normal breast tissue to the Komen Tissue Bank (KTB) at Indiana University Simon Cancer Center, (2) intermediate risk: 15 women with biopsy-identified benign breast disease (BBD), and (3) high risk: 19 prophylactic mastectomies from women with germline mutations in BRCA1/2 genes. We performed immunohistochemical stains and analysis to quantitate immune cell densities from digital images in up to 10 representative lobules per sample. Median cell counts per mm2 were compared between groups using Wilcoxon rank-sum tests. RESULTS: Normal/benign breast lobules from BRCA carriers had significantly higher densities of immune cells/mm2 compared to KTB normal donors (all p < 0.001): CD8 + 354.4 vs 150.9; CD4 + 116.3 vs 17.7; CD68 + 237.5 vs 57.8; and CD11c + (3.5% vs 0.4% pixels positive). BBD tissues differed from BRCA carriers only in CD8 + cells but had higher densities of CD4 + , CD11c + , and CD68 + immune cells compared to KTB donors. CONCLUSIONS: These preliminary analyses show that normal/benign breast lobules of BRCA mutation carriers contain increased immune cells compared with normal donor breast tissues, and BBD tissues appear overall more similar to BRCA carriers.

Fracture Toughness Characteristics of Stacked Bilayer Graphene via Far-Field Displacement Measurements.

Mechanical properties of graphene, e.g., strength, modulus, and fracture toughness are extremely sensitive to flaws. Here the fracture properties of stacked bilayer graphene sheets (SBLG) are reported, obtained via stacking two individually grown graphene sheets. The SBLG is presented here as a building block for flaw-resilient nanomaterials. The fracture properties of freestanding SBLG sheets, suspended on transmission electron microscope (TEM) grids, are characterized by stretching the TEM grid inside an scanning electron microscope (SEM) chamber and monitoring the local displacements in real-time. The fracture toughness is measured and expressed as a function of the critical displacement required to propagate existing cracks in the experiment via computational models. This approach decouples force and displacements measurements, and utilizes the known elastic modulus along with the known displacement boundary conditions at the onset of crack growth to estimate the far field force and stress. This strategy represents a breakthrough in nanoscale fracture mechanics for statistical analysis and high throughput experimens on multiple samples at a time. Results demonstrate that the SBLG is markedly tougher than as-grown single or multilayer graphene, with a mode I fracture toughness of ≈28.06 ± 7.5 MPa m $\sqrt m $ . The mechanisms leading to a higher toughness of SBLG are also analyzed and discussed.

Colchicine usage for prevention of post atrial fibrillation ablation pericarditis in patients undergoing high-power short-duration ablation.

INTRODUCTION: Radiofrequency ablation (RFA) for atrial fibrillation (AF) has been associated with variable incidence (0.88%-10%) of pericarditis manifested as chest pain, possibly more prevalent with the advent of high-power short-duration (HPSD) ablation. This has led to the widespread use of colchicine in preventative protocols for postablation pericarditis. However, the efficacy of preventative colchicine has not been validated yet. OBJECTIVE: To evaluate the efficacy of a routine postoperative colchicine regimen (0.6 mg twice a day for 14 days post-AF ablation) for prevention of postablation pericarditis in patients undergoing HPSD ablation. METHOD: We retrospectively evaluated consecutive single-operator HPSD AF ablation procedures at our institution from June 2019 to July 2022. A colchicine protocol was introduced in June 2021 for the prevention of postablation pericarditis. All ablations were performed with 50 watts. Patients were divided into colchicine and noncolchicine groups. We recorded incidence of postablation chest pain, emergency room (ER) visit for chest pain, pericardial effusion, pericardiocentesis, any ER visit, hospitalization, AF recurrence, and cardioversion for AF within the first 30 days following ablation. We also recorded colchicine-related side effects and medication compliance. RESULTS: Two hundred and ninety-four consecutive HPSD AF ablation patients were screened for the study. After implementing the prespecified exclusion criteria, a total of 205 patients were included in the final analysis, yielding 101 patients in the colchicine group and 104 patients in the noncolchicine group. Both groups were well-matched for demographic and procedural parameters. There was no significant difference in postablation chest pain (9.9% vs. 8.6%, p = .7), pericardial effusion (2.9% vs. 0.9%, p = .1), ER visits (11.9% vs. 12.5%, p = .2), 30-day hospitalization for AF recurrence (0.9% vs. 0.96%, p = .3), and 30-day need for cardioversion for AF (3.9% vs. 5.7%, p = .2). Fifteen (15) patients had severe colchicine-related diarrhea, out of which 12 discontinued it prematurely. There were no major procedural complications in either group. CONCLUSION: In this single-operator retrospective analysis, prophylactic colchicine was not associated with significant reduction in the incidence of postablation chest pain, pericarditis, 30 day hospitalization, ER visits, or AF recurrence or need of cardioversion within first 30 days after HPSD ablation for AF. However, its usage was associated with significant diarrhea. This study concludes no additional advantage of prophylactic use of colchicine after HPSD AF ablation.

Inconsistent Outcome Reporting in Heart Failure Randomized Controlled Trials.

BACKGROUND: Randomized controlled trials (RCTs) may report outcomes different from those prespecified on trial-registration websites, protocols and statistical analysis plans (SAPs). This study sought to investigate the prevalence and characteristics of heart failure (HF) RCTs that report outcomes different from those prespecified. METHODS AND RESULTS: MEDLINE via PubMed was searched to include phase II-IV HF RCTs in 9 high-impact journals from 2010 to 2020. Outcomes reported in trial publications were compared with prespecified outcomes in protocols, registration websites and SAPs. We used the χ2 or Fisher exact test to analyze correlations between trial characteristics and inconsistencies. Among 216 trials, 32 inconsistencies were observed in 28 trials (13.0%). Among 32 inconsistencies, 2 (6.3%) pertained to omission of prespecified primary outcomes, 4 (12.5%) to omission of prespecified secondary outcomes, 2 (6.3%) to changing prespecified primary outcomes to secondary outcomes, and 2 (6.3%) to changing prespecified secondary outcomes to primary outcomes. Of the inconsistencies, 3 (9.4%) pertained to addition of new primary outcomes, 17 (53.1%) to addition of new secondary outcomes, and 2 (6.3%,) to changes in the timing of assessment of primary outcomes. The majority of the inconsistencies favored statistically significant findings; 78 (36.1%) were registered retrospectively. Single-center recruitment was associated with outcome inconsistencies (ß = -0.14; 95% CI, -0.22 - -0.01; P = 0.035). CONCLUSIONS: More than 1 in 10 trials reported outcomes inconsistent with those specified in trial registration websites, SAPs and protocols. An action plan is warranted to minimize selective reporting and improve transparency.

Relative biochemical and physiological docking of cucumber varieties for supporting innate immunity against Podosphaera xanthii.

Powdery mildew in cucumber is caused by the Podosphaera xanthii. No strategy for improving disease resistance can be successful in the absence of thorough insights into the physiological and biochemical responses of cucumber plants to powdery mildew. Therefore, a field experiment was executed to evaluate five commercial cucumber varieties (V1: Dynasty, V2: Long green, V3:Desi Kheera, V4:Thamin II, V5:Cucumber 363) for their inherent immunity to powdery mildew. Upon inoculating cucumber plants with Podosphaera xanthii, we noted differential responses among the varieties. Compared to other varieties, V1 and V2 showed higher values (P ≤ 0.05) for chlorophyll-a under control and pathogen-attacked plants respectively. The minimum value of anthocyanin content (-53.73%) was recorded in V3 as compared to other varieties post pathogen infection. All pathogen-infected cucumber varieties showed a considerable (P ≤ 0.05) loss in flavonoid content except V2. The maximum destruction for Phenolics under powdery mildew (179%) were recorded in V4, whereas V1 exhibited maximum phenolic content under control conditions. In pathogen-infected plants, the minimum AsA was recorded in V5 as compared to all other varieties. Pathogen invasion impacted significantly (P ≤ 0.05) the activity of superoxide dismutase (SOD). Besides, cucumber plants after pathogen inoculation resulted in a considerable (P ≤ 0.05) increase of peroxidase (POD) activity in V1 (5.02%), V2 (7.5%), and V3 (11%) in contrast to V4. Our results confirmed that cucumber varieties perform differently, which was brought on by distinct metabolic and physiological modifications that have an impact on growth and development. The changes in different attributes were correlated with cucumber resistance against powdery mildew. The results would help us fully harness the potential of these varieties to trigger disease management initiatives and defense responses.

Improved Transdermal Delivery of Rabies Vaccine using Iontophoresis Coupled Microneedle Approach.

AIM: This study was aimed to develop rabies vaccine incorporated microneedle (MN) patches and evaluate the immunogenicity of prepared formulations in combination with iontophoresis. METHODS: Patches comprising of polyvinyl pyrrolidone, hyaluronic acid and polyethylene glycol 400 were engineered by vacuum micromolding technique. Physical evaluation of patches included determination of folding endurance, % swelling and morphological features. In vitro release study was performed in skin simulant agarose gel using model drug (methylene blue) loaded patches. In vitro insertion ability was assessed using stratum corneum simulant parafilm. In vivo insertion study was performed in rats. Immunogenicity was evaluated in dogs by determining immunoglobulin G (IgG) and rabies virus neutralizing antibodies (RVNA) titer. RESULTS: Patches displayed uniformly distributed microprojections with pointed tips and smooth surface, ~ 70% swelling, remained intact for ~ 200 foldings and successfully penetrated the parafilm. The area covered by model drug across agarose gel was almost double following treatment with MN-iontophoresis combination (MNdi) compared to MN alone (MNdo). Histological examination of rat skin treated with vaccine laden MN (MNvo) and MN-iontophoresis combination (MNvi) confirmed the formation of grooves in epidermis without any damage to the deep vasculature. A ~ 73% and ~ 206% increase (compared to untreated counterpart) was observed in the IgG titer of MNvo and MNvi treated dogs, respectively. The RVNA titer was increased by ~ 1.2 and ~ 2.2 times (compared to threshold value) after MNvo and MNvi treatment, respectively. CONCLUSION: MN-iontophoresis combination provided relatively potent immunogenic response over the conventional intramuscular injection, hence, can be used for administering vaccines transcutaneously.

Bioremediation of heavy metals polluted environment and decolourization of black liquor using microbial biofilms.

BACKGROUND: With increased urbanization and industrialization, modern life has led to an anthropogenic impact on the biosphere. Heavy metals pollution and pollutants from black liquor (BL) have caused severe effects on environment and living organisms. Bacterial biofilm has potential to remediate heavy metals and remove BL from the environment. Hence, this study was planned to investigate the potential of microbial biofilms for the bioremediation of heavy metals and BL polluted environments. METHODS AND RESULTS: Eleven biofilm forming bacterial strains (SB1, SB2, SC1, AF1, 5A, BC-1, BC-2, BC-3, BC-4, BC-5 and BC-6) were isolated and identified upto species level via 16S rRNA gene sequencing. Biofilm strains belonging to Bacillus and Lysinibacillus sphaericus were used to remediate heavy metals (Pb, Ni, Mn, Zn, Cu, and Co). Atomic absorption spectroscopy showed significantly high (P ≤ 0.05) bioremediation potential by L. sphaericus biofilm (1462.0 ± 0.67 µgmL-1) against zinc (Zn). Similarly, Pseudomonas putida biofilm significantly (P ≤ 0.05) decolourized (65.1%) BL. Fourier transform infrared (FTIR) analysis of treated heavy metals showed the shifting of major peaks (1637 & 1629-1647, 1633 & 1635-1643, and 1638-1633 cm-1) corresponding to specific amide groups due to C = O stretching. CONCLUSION: The study suggested that biofilm of the microbial flora from tanneries and pulp paper effluents possesses a strong potential for heavy metals bioremediation and BL decolourization. To our knowledge, this is the first report showing promising biofilm remediation potential of bacterial flora of tanneries and pulp-paper effluent from Kasur and Sheikhupura, Punjab, Pakistan, against heavy metals and BL.

Meta-Analysis Evaluating Risk of Hyperkalemia Stratified by Baseline MRA Usage in Patients with Heart Failure Receiving SGLT2 Inhibitors.

BACKGROUND: Both mineralocorticoid receptor antagonists (MRAs) and sodium-glucose co-transporter type 2 inhibitors (SGLT2is) have demonstrated beneficial reductions in cardiovascular outcomes. However, the risk of precipitating hyperkalemia with their concomitant usage remains unclear. METHODS: MEDLINE and Cochrane were searched from inception through March 2022. Randomized controlled trials on patients with heart failure (HF) evaluating the effect of SGLT2is on clinical outcomes between MRA users and non-users were considered for inclusion. Outcomes of interest were mild and moderate/severe hyperkalemia, for which hazard ratios (HR) were pooled using a random effects model. RESULTS: From the 972 articles retrieved from the initial search, three RCTs (n = 14,462 patients) were included in our meta-analysis. Pooled analysis demonstrated no significant difference in the incidence of mild hyperkalemia between MRA users (HR 0.82 [0.70-0.97]) and non-users (HR 0.95 [0.77-1.17]) (P-interaction = 0.28). The risk of severe hyperkalemia was significantly decreased in MRA users (HR 0.59 [0.44-0.78]; p = 0.0002; I2 = 0%) but not in non-users (HR 0.76 [0.56-1.02]; p = 0.07; I2 = 0%) (P-interaction = 0.22). Sensitivity analysis including patients with HF with reduced ejection fraction (HFrEF) revealed similar results across all subgroups, but no significant reduction in the incidence of mild hyperkalemia (HR 0.89 [0.76-1.04] was noted in MRA users with HFrEF. CONCLUSION: MRAs reduced the risk of mild or moderate/severe hyperkalemia, when added to SGLT2is. Future clinical trials should target scrupulous assessment of the risk of mild and moderate/severe hyperkalemia when used concomitantly with MRAs.