Reduction In Count Research Articles

The Effect of Long-Term Azithromycin on Objective and Subjective Cough in Chronic Respiratory Disease: A Systematic Review and Meta-analysis of Randomised Controlled Trials and Noncomparative Studies.

Azithromycin is an effective treatment for various respiratory conditions but its effect on cough is poorly understood. We synthesised data from randomised controlled trials (RCTs) and noncomparative studies (NCT) examining its effect on objective and subjective cough. After prospective registration on PROSPERO, we searched MEDLINE, EMBASE, and CENTRAL for both RCTs and NCT trials examining the effect azithromycin on cough in respiratory disease. We identified 1240 studies of which 6 (4 RCTs and 2 NCT studies) were included in the meta-analysis, with a total of 275 patients. Azithromycin was associated with significant improvement in Leicester Cough Questionnaire scores at follow-up when compared to baseline scores (SMD = 0.62 [95% CI 0.12 to 1.12], p = 0.01). However, when only RCTs were synthesised, no significant effect was observed (SMD = 0.12 [95% CI -0.36 to 0.60], p = 0.62). There was no significant reduction in cough severity VAS score (SMD = -0.39 [95% CI -0.92 to 0.14], p = 0.15). There was no significant reduction in objective cough count (SMD = -0.41 [95% CI -1.04 to 0.32], p = 0.09). Azithromycin therapy improves cough-related quality of life in various chronic respiratory diseases; however, there was no significant effect on cough outcomes when only data from RCTs were synthesised. We believe that to accurately identify which patients whose cough would benefit from azithromycin a large-scale clinical trial of patients with a broad spectrum of respiratory diseases, with sufficiently severe cough, should be undertaken with subgroup analysis of individual disease areas.

RBCs Regulate Platelet Function and Hemostasis under Shear Conditions through Biophysical and Biochemical Means.

Red blood cells (RBCs) have been hypothesized to support hemostasis by facilitating platelet margination and releasing platelet-activating factors such as adenosine diphosphate (ADP). Significant knowledge gaps remain regarding how RBCs influence platelet function, especially in (patho)physiologically relevant hemodynamic conditions. Here we present results showing how RBCs affect platelet function and hemostasis in conditions of anemia, thrombocytopenia, and pancytopenia, and how the biochemical and biophysical properties of RBCs regulate platelet function at the blood-vessel wall interface and in the fluid phase under flow conditions. We found that RBCs promoted platelet deposition to collagen under flow conditions in moderate (50  103/L) but not severe (10  103/L) thrombocytopenia in vitro. Reduction in hematocrit by 45% led to increased bleeding in mice with hemolytic anemia. In contrast, bleeding diathesis was observed in mice with a 90% but not with a 60% reduction in platelet counts. RBC transfusion improved hemostasis by enhancing fibrin clot formation at the site of vascular injury in mice with severe pancytopenia induced by total body irradiation. Altering membrane deformability changed the ability of RBCs to promote platelet aggregation. RBC-derived ADP contributed to platelet activation and aggregation in vitro under pathologically high shear stresses, as observed in patients supported by left ventricular assist devices. These findings demonstrate that RBCs support platelet function and hemostasis through multiple mechanisms, both at the blood-vessel wall interface and in the fluidic phase of circulation.

High rates of benzimidazole-resistance-associated alleles in Haemonchus contortus and detection of resistance against macrocyclic lactones in strongylids from German alpaca herds

The population of South American camelids (SAC) has been steadily growing in Europe, where they are confronted with the regional endoparasite population of ruminants. As there are no anthelmintic drugs registered for use against nematode infections in SACs, anthelmintics (AH) available for ruminants or horses are usually applied. Reports indicating potential failures in administered AH are increasing. However, the generally low egg counts in SACs complicate the application of resistance tests in the field. The present study reports a follow-up study on SAC farms where anthelmintic resistance (AR) was suspected. The aims were (i) to repeat faecal egg count reduction tests (FECRTs) on potentially affected farms identified in a previous study with larger sample sizes, (ii) to verify suspected AR of Haemonchus contortus against benzimidazoles (BZ) by performing a single-nucleotide polymorphism (SNP) analysis using digital polymerase chain reaction (dPCR), and (iii) to apply the mini-FLOTAC technique for more reliable results at low egg counts in line with current recommendations. Seven farms (9–46 animals each) were examined by coproscopy, larval differentiation and SNP analysis. A FECRT was performed on six of these farms with moxidectin (three farms), monepantel (two farms) and ivermectin (one farm). The FEC was calculated according to the current World Association for the Advancement of Veterinary Parasitology (WAAVP) guidelines with the clinical protocol (a newly introduced variant of FECRT which can be used for smaller sample sizes and lower egg counts on the cost of sensitivity) and an expected efficacy of 99%. A high level (> 90%) of BZ-resistance-associated SNPs on codon 200 of H. contortus was observed on all farms. With the FECRT, resistance was demonstrated for ivermectin (74% FECR), while it remained inconclusive for one farm for moxidectin treatment. Sustained efficacy was demonstrated for the remaining treatments. This study showed an advanced level of BZ resistance in H. contortus of SACs and the development of AR against macrocyclic lactones on some farms. Thus, constant monitoring of AH treatment and sustainable worm control methods both need to be applied.Graphical

The effect of anthelmintic treatment and efficacy on the faecal microbiota of healthy adult horses

Changes to the faecal microbiota of horses associated with administration of anthelmintic drugs is poorly defined. This study included horses with cyathostomin infection where susceptibility and resistance to oxfendazole and abamectin was known. This study assessed the changes to the faecal microbiota associated with administration of two different anthelmintics in this population. Twenty-four adult horses were included. Faecal egg counts were performed on all horses prior to random allocation into abamectin (n=8), oxfendazole (n=8) or Control groups (n=8) and at Day 14 post treatment. Faecal samples were collected for microbiota analysis prior to anthelmintic administration and on Day 3 and Day 14. From each faecal sample, DNA was extracted prior to PCR amplification, next generation sequencing and analysis using QIIME2. Anthelmintic treatment was associated with changes in alpha diversity (p <0.05), with increased evenness and diversity at Day 14 and increased richness at Day 3 within the abamectin group. Differences in relative abundance of bacteria at the phyla, family and genus taxonomic levels occurred after treatment; indicating that the microbiota was altered with anthelmintic administration. The results support that anthelmintic administration and removal of cyathostomins from the large intestine of horses is associated with changes in the faecal microbiota. The results suggest that removal of cyathostomins is associated with greater differences in microbiota, compared to anthelmintic drug administration that is ineffective in reducing cyathostomin infection. Cyathostomin removal was supported by adequate reduction of faecal egg counts, determined by faecal egg count reduction testing.

Clinical and microbial evaluation of mouthwash containing Achyranthes aspera and Trachyspermum ammi: A randomized controlled non-inferiority trial

ObjectivesAchyranthes aspera (Apamarga) and Trachyspermum ammi (Ajwain) have been used in many clinical conditions, and it displays valuable properties as an alternative to Chlorhexidine (CHX) in the management of gingivitis. Therefore, this study aims to assess the effect of Achyranthes aspera and Trachyspermum ammi (AA + TA) based herbal mouthwash, 0.2 % CHX, and placebo mouthwash on gingival health, plaque control and antibacterial activity against specific periodontal pathogens (Porphyromonas gingivalis and Tannerella forsythia) using quantitative real-time PCR (RT-PCR). MethodsThis was a randomized controlled non-inferiority trial involving 108 children with plaque-induced gingivitis who were randomly assigned to three groups of 36 children each: Group A, AA + TA mouthwash; Group B, CHX mouthwash; and Group C, placebo mouthwash. Gingival index and plaque index were recorded at baseline, 7th and 21st day. RT-PCR was employed to determine the bacterial counts of each plaque sample at baseline and after 21 days. ResultsAll three groups exhibited a gradual and significant reduction in both gingival and plaque scores from baseline to days 7 and 21. However, the placebo group did not demonstrate a significant difference in scores between days 7 and 21. Furthermore, a significant reduction in bacterial counts of P. gingivalis and T. forsythia was observed in the groups receiving CHX and AA + TA mouthwash after 21 days of intervention compared to the placebo group. ConclusionAA + TA mouthwash demonstrated non-inferiority in anti-gingivitis and anti-plaque properties compared to CHX, suggesting its potential suitability as an alternative to CHX when used in conjunction with mechanical plaque control measures.

Efficacy of a new generation topical retinoid in the treatment of patients with moderate to severe acne on the face and trunk

Rationale. The extreme prevalence of acne, long-term course and multifactorial pathogenesis necessitate the development of new drugs and treatment methods aimed at increasing efficiency and achieving clinical effects in the shortest possible time. This article presents data from two international clinical studies to determine the effectiveness and safety of trifarotene 50 µg/g (0.005%) cream in the treatment of patients with moderate acne on the face and trunk. The purpose of the study. To evaluate the safety and effectiveness of trifarotene cream, 0.005%, a new topical retinoid, for moderate acne of the face and trunk. Material and research methods. Two international, double-blind, randomized, placebo (vehicle) controlled, 12-week phase III studies screened 2817 and randomized 2420 patients 9 years of age and over. The effectiveness of the drug was assessed based on the registration of the number of patients who achieved the effect of “clear” or “almost clear” skin condition and an improvement of ≥ 2 points in terms of IGA on the facial skin and PGA on the truncal skin during 12 weeks of treatment, as well as by calculating the change in absolute number of inflammatory and non-inflammatory acne elements relatively to the initial level. The safety of therapy was assessed based on the registration of adverse events, local tolerability (the formation and severity of retinoic dermatitis), abnormalities in vital signs and the results of standard laboratory tests. Results. The onset of effect of trifarotene versus that of its vehicle was rapid, with significant reductions in both inflammatory and noninflammatory lesion counts seen as early as 1 week after treatment on the face and as early as 2 weeks after treatment on the trunk. In both studies, at week 12 the facial success rates according to IGA and PGA and change in inflammatory and noninflammatory lesion counts (both absolute and percentage) were all highly significant (P0.001) in favor of trifarotene when compared with the vehicle and the formation of the “almost clear” and “clean” effect was registered in the vast majority of patients, who used cream with 0.005% trifarotene. Conclusion. The results of the study demonstrated the pronounced clinical effectiveness of trifarotene cream 0.005% in the treatment of patients with moderate acne on the skin of the face and trunk.

P-603 Combined oral contraceptive pill (COCP) before controlled ovarian hyperstimulation (COH) in donors could negatively affect egg donation outcomes in recipients: a multicentre retrospective study

Abstract Study question Could COCP use before COH with a progestin primed ovarian stimulation protocol (PPOS) in donors also negatively influence the egg donation outcomes in recipients? Summary answer Synchronization with a combined oral contraceptive pill (COCP) before controlled ovarian hyperstimulation (COH) involving progestin for pituitary suppression shows worst outcomes in egg donation treatments. What is known already It is well known that COCP leads to a long-lasting pituitary suppression, a reversible reduction in AMH and antral follicle count with higher risk of inappropriate response to COH and GnRH-agonist trigger, potentially reducing number and quality of retrieved oocytes. This is supported by the latest international guidelines on COH that strongly discourage COCP use before GnRH antagonist protocols because of a reduced efficacy of such cycles, also, in terms of ongoing pregnancy rate (OPR). They also underlie that interactions between COCP pretreatment and PPOS protocols remain inadequately explored and more research are needed to clarify discrepancies persisting in literature. Study design, size, duration Multicentre retrospective cohort study evaluating egg donation outcomes, depending on the use or not of COCP pre-treatment in donors, in terms of OPR, Live Birth Rate (LBR), and secondly of fertilization rate (FR), blastulation rate (BR), implantation rate (IR) and miscarriage rate (MR). The treatments were realized in a Private Fertility Clinic (where donors also underwent COH with PPOS protocol) and a public hospital (transnational egg donation program) between January 2022 and September 2023. Participants/materials, setting, methods 216 egg donation cycles were studied. Excluding cases of fertilization and/or embryo development failure and cases for which embryo transfer outcomes were not available at the time of data collection, the study analysed the outcomes of 90 embryo transfers (ETs). After the first analysis on total cycles, a stratification was made to evaluate whether COCP could have a different influence depending on the oocytes type used: fresh or vitrified. Main results and the role of chance COCP-No and COCP-Yes groups show similar FR and BR, after donation of same oocytes number (6,4 ± 1,1 vs 6,5± 1). Interestingly, vitrified oocytes from COCP-Yes donors produced a statistically lower yield of viable blastocysts (22,2% versus 37,9%; p = 0,007). IR was higher in the COCP-No group, (46,4% vs. 28,6%), data confirmed also in the two subgroups (fresh: 42,9% vs. 14,3%; vitrified: 48,8% vs. 35,7%). Higher MR was observed in the COCP-Yes group, achieving statistical significance both for total oocytes (66,7% vs. 9,4%; p = 0,006) and vitrified ones (60% vs. 5%; p = 0,016). Pregnancy rate was higher in the COCP-No group (46,4% vs. 28,6%), the same trend was found regardless of the type of oocytes used (fresh: 42,9% vs. 14,3%; vitrified: 48,8% vs. 35,7%). The greatest discrepancies were observed in OPR and LBR subcategories. In fact, a statistically higher OPR was obtained in the COCP-No group (42% vs. 9,5%, p = 0,008), which leads to a statistically higher LBR (30,4% vs. 0%; p = 0,004). Notably, the LBR after using both fresh and vitrified oocytes was markedly higher in the COCP-No group (fresh: 28,6% vs. 0%, p = 0,385; vitrified: 31,7% vs. 0%, p = 0,041), presenting a significant difference when vitrified oocytes were used with potential clinical relevance. Limitations, reasons for caution The main limitation lies in the retrospective nature of the study and the small sample size, but the multicentre design gives greater reliability. Further research is needed to confirm these findings and better understand the specific circumstances in which COCP may or may not be beneficial. Wider implications of the findings COCP pretreatment in egg donors undergoing PPOS protocol may negatively impact embryo development and pregnancy outcomes in recipients, with increased MR, and reduced OPR, and LBR. Particularly, the worst outcomes involve vitrified oocytes, providing valuable insights to reconsider COCP use in transnational egg donation programs, but also fertility preservation ones. Trial registration number Not Applicable

P-353 Perfluorooctanoic acid (PFOA) impacts murine ovarian follicle development through apoptotic signaling pathways and exhibits transgenerational effects

Abstract Study question How does Perfluorooctanoic Acid (PFOA) exposure impact ovarian function and the physiological and reproductive health of subsequent offspring? Summary answer PFOA exposure leads to ovarian dysfunction, characterized by follicular depletion and hormonal imbalances, and adversely affects the reproductive health of offspring. What is known already Mass spectrometry reveals higher perfluorinated compound levels in premature ovarian failure patients compared to healthy individuals. PFOA, an environmental contaminant, is known for its endocrine-disrupting effects, but its specific impact on ovarian function and transgenerational health remains less explored. This study addresses the gap by examining PFOA’s direct ovarian effects and its consequential impacts on offspring, using both in vivo and in vitro models. Study design, size, duration This study employs mouse models and ovarian granulosa cells to assess PFOA’s impact. Mice were administered PFOA (50mg/Kg) and evaluated for ovarian function and offspring health. Ovarian tissue underwent histological analysis and hormone assays. RNA transcriptome sequencing identified activated apoptotic pathways post-PFOA exposure. Offspring physiological and reproductive parameters were also examined. Parallel in vitro experiments with ovarian granulosa cells at 50uM PFOA concentration provided insights into cellular apoptosis. Participants/materials, setting, methods Clinically, we collected serum samples from approximately 100 Premature Ovarian Insufficiency (POI) patients and 100 healthy individuals, analyzed using mass spectrometry. In murine experiments, we simulated human environmental exposure to PFOA (particularly in high-exposure professions) using a 50mg/Kg dose administered via gavage. Transcriptome sequencing analyzed potential signaling pathways in both experimental and control mice. Offspring underwent physiological metabolic assessments and fertility evaluations, including fertilization and blastocyst rates. Main results and the role of chance Mass spectrometry results from human samples revealed significantly higher levels of perfluorinated compounds in POI patients compared to healthy controls, suggesting a potential link between PFOA exposure and ovarian dysfunction. In murine models, PFOA administration at 50mg/Kg resulted in notable ovarian changes. Histological analysis showed a reduction in follicle counts and abnormalities in AMH and FSH levels, indicative of premature ovarian failure. Transcriptome sequencing of these mice highlighted the activation of apoptotic pathways, especially the PI3K/Akt/mTOR signaling, post-PFOA exposure. This suggests a mechanistic pathway through which PFOA may induce ovarian dysfunction. Furthermore, offspring of PFOA-exposed mice displayed significant reproductive health challenges. They exhibited irregularities in estrous cycles and a decrease in oocyte fertilization rates, pointing to potential transgenerational effects of PFOA exposure. These findings in murine models align with the elevated perfluorinated compound levels observed in human POI patients, reinforcing the hypothesis of PFOA’s detrimental impact on ovarian health and subsequent generational fertility. The consistency of results across human clinical data and animal models strengthens the argument for a causal relationship between PFOA exposure and reproductive health risks. Limitations, reasons for caution While these findings highlight PFOA’s detrimental effects on ovarian function and offspring health, translating results from animal models to humans necessitates caution. The specific mechanisms and potential variability in human response to environmental PFOA exposure require further investigation. Wider implications of the findings This research underscores the far-reaching impacts of environmental contaminants like PFOA on reproductive health. It emphasizes the need for stringent regulation of such pollutants and further studies to understand their long-term effects on human health, particularly regarding fertility and intergenerational wellbeing. Trial registration number not applicable

Unravelling the Effectiveness of Anthelmintic Treatments on Equine Strongyles on Irish Farms

Over the preceding decades, the widespread dependence on anthelmintic drugs for managing nematodes in grazing equids has given rise to resistance against commonly used anthelmintics in various countries. This study explores the prevalence of anthelmintic resistance across 44 horse farms in Ireland. Anthelmintic efficacy was evaluated through fecal egg count reduction (FECR) tests employing the mini-FLOTAC technique. Resistance to benzimidazoles was identified in 12 out of 14 farms (FECR range: 0.00% to 86.2%). Ivermectin resistance was observed on two farms, one with an FECR of 80.70% and another with an FECR of 96.10% (lower 95% high probability density interval (HPD) &lt;90%, 11.70%). On the remaining six farms, the reduction with ivermectin still exceeded 95%. The reduced efficacy of moxidectin was noted on two farms (FECR = 86.90% and 93.50%) and on a third farm with an FECR of 99.50 and a lower HPD interval &lt; 90% at 24.00%. In summary, these findings emphasize the urgent need for alternative strategies in equine strongyle control that reduce reliance on anthelmintics and prioritize effective management practices on Irish equine farms to hinder the impending development of drug-resistant parasite populations.

The long-term outcomes of mepolizumab treatment at 100 mg dose on idiopathic chronic eosinophilic pneumonia: A real-life experience.

Background: The standard therapeutic regimen for idiopathic chronic eosinophilic pneumonia (ICEP) involves the administration of oral corticosteroids (OCS). However, a notable proportion of individuals experience recurrent episodes after the tapering or cessation of OCS during the course of ICEP. There has been a growing interest in exploring alternative treatment modalities for patients with ICEP at heightened risk of relapse. Objective: The aim of this study was to assess the efficacy of mepolizumab at a dose of 100 mg administered every 4 weeks in preventing relapses of ICEP and its impact on the clinical outcomes. Methods: This retrospective clinical observational study used real-world data to assess the impact of mepolizumab on patients diagnosed with ICEP accompanied by severe asthma. Demographic information and clinical characteristics were extracted from medical records. The study examined the effect of mepolizumab on the annual relapse rate, OCS dose, eosinophil count, and respiratory function parameters. Results: All patients included in the study, with a median (range) follow-up period of 19 months (4-40 months), the annual relapse rate decreased from 0.33 to 0 after the initiation mepolizumab. In addition, the maintenance OCS dose, expressed in methylprednisolone equivalents, declined from 4 mg/day to 0 mg/day. A reduction in the blood eosinophil count was observed, alongside a partial improvement in respiratory function test results among the patients. Conclusıon: A dose regimen of 100 mg of mepolizumab administered every 4 weeks emerges as a promising and well-tolerated therapeutic approach for averting relapses of ICEP.

CLADIN- CLADribine and INnate immune response in multiple sclerosis – A phase IV prospective study

Cladribine (Mavenclad®) is an oral treatment for relapsing remitting MS (RRMS), but its mechanism of action and its effects on innate immune responses in unknown. This study is a prospective Phase IV study of 41 patients with RRMS, and aims to investigate the mechanism of action of cladribine on peripheral monocytes, and its impact P2X7 receptor. There was a significant reduction in monocyte count in vivo at week 1 post cladribine administration, and the subset of cells being most impacted were the CD14lo CD16+ ‘non-classical’ monocytes. Of the 14 cytokines measured in serum, CCL2 levels increased at week 1. In vitro, cladrabine induced a reduction in P2X7R pore as well as channel activity. This study demonstrates a novel mechanism of action for cladribine. It calls for studying potential benefits of cladribine in progressive forms of MS and other neurodegenerative diseases where innate immune related inflammation is implicated in disease pathogenesis.

High throughput screening identifies dasatinib as synergistic with trametinib in low grade serous ovarian carcinoma

BackgroundLow grade serous ovarian carcinoma (LGSOC) is a distinct histotype of ovarian cancer characterised high levels of intrinsic chemoresistance, highlighting the urgent need for new treatments. High throughput screening in clinically-informative cell-based models represents an attractive strategy for identifying candidate treatment options for prioritisation in clinical studies. MethodsWe performed a high throughput drug screen of 1610 agents across a panel of 6 LGSOC cell lines (3 RAS/RAF-mutant, 3 RAS/RAF-wildtype) to identify novel candidate therapeutic approaches. Validation comprised dose-response analysis across 9 LGSOC models and 5 high grade serous comparator lines. Results16 hits of 1610 screened compounds were prioritised for validation based on >50% reduction in nuclei counts in over half of screened cell lines at 1000 nM concentration. 11 compounds passed validation, and the four agents of greatest interest (dasatinib, tyrosine kinase inhibitor; disulfiram, aldehyde dehydrogenase inhibitor; carfilzomib, proteasome inhibitor; romidepsin, histone deacetylase inhibitor) underwent synergy profiling with the recently approved MEK inhibitor trametinib. Disulfiram demonstrated excellent selectivity for LGSOC versus high grade serous ovarian carcinoma comparator lines (P = 0.003 for IC50 comparison), while the tyrosine kinase inhibitor dasatinib demonstrated favourable synergy with trametinib across multiple LGSOC models (maximum zero interaction potency synergy score 46.9). The novel, highly selective Src family kinase (SFK) inhibitor NXP900 demonstrated a similar trametinib synergy profile to dasatinib, suggesting that SFK inhibition is the likely driver of synergy. ConclusionDasatinib and other SFK inhibitors represent novel candidate treatments for LGSOC and demonstrate synergy with trametinib. Disulfiram represents an additional treatment strategy worthy of investigation.

An approach to combat multidrug-resistant K. pneumoniae strain using synergistic effects of Ocotea diospyrifolia essential oil in combination with Amikacin

The natural antimicrobial properties of essential oils (EOs) have contributed to the battle against multidrug-resistant microorganisms by providing new ways to develop more effective antibiotic agents. In this study, we investigated the chemical composition of Ocotea diospyrifolia essential oil (OdOE) and its antimicrobial properties combined with amikacin (AMK). Through gas chromatography-mass spectrometry (GCMS) analysis, the primary constituents of OdOE were identified as α-bisabolol (45.8%), β-bisabolene (9.4%), γ-elemene (7.6%), (Z)- β-farnesene (5.2%), spathulenol (3.5%), (Z)-caryophyllene (3.3%), and (E)-caryophyllene (3.1%). In vitro assessments showed that the combined administration of OdOE and AMK exerted a synergistic antibacterial effect on the multidrug-resistant K. pneumoniae strain. This synergistic effect demonstrated bacteriostatic action. OdEO combined with amikacin showed protein extravasation within 2 h of treatment, leading to bacterial death, which was determined by a reduction in viable cell count. The effective concentrations showed hemocompatibility. In vivo assessments using Caenorhabditis elegans as a model showed the survival of 85% of infected nematodes. Therefore, the combination OdEO combined with amikacin exhibited antimicrobial activity against a multidrug-resistant K. pneumoniae strain. Thus, OdOE is a promising agent that may be considered for development of antimicrobial treatment.

Response of selected scion and rootstock grape (&lt;i&gt;Vitis &lt;/i&gt;spp.) genotypes to induced drought stress

Climate change is expected to elevate drought frequency, straining agricultural freshwater resources. Developing drought-tolerant grapevine varieties is crucial. This study examined grape scion and rootstock genotypes under well-watered (WW) and induced-drought (ID) conditions. ID treatment reduced vine length by 11.34-35.15%, with Vitis parviflora, 110R, and Male Hybrid rootstocks showing superior growth. Root length increased under ID, indicating an adaptive moisture-seeking response. The ID treatment led to substantial reduction in leaf count and average leaf area, especially in Flame Seedless (27.71 and 19.07 cm2, respectively). Drought stress elevated chlorophyll a:b ratio, affecting chlorophyll degradation in different genotypes. Significant variations were observed in leaf and root iron (Fe) and zinc (Zn) contents. Enzyme activities particularly peroxidase and polyphenol oxidase especially rose under drought, particularly in V. parviflora (3.39 μM guaiacol min-1 mg-1 protein and 1.33EU/ml/min respectively) likely to be contributing in drought tolerance mechanism. Principal component analysis (PCA) highlighted impact of traits on genotypes, emphasizing V. parviflora, Male Hybrid and Pusa Navrang as superior drought stress tolerant genotypes. Genotype clustering confirmed distinct groupings, while, correlation analysis unveiled intricate trait interactions.

Efficacy of topical treatments for mild‐to‐moderate acne: A systematic review and meta‐analysis of randomized control trials

AbstractAcne is a common skin condition, but little data exist on the comparative efficacy of topical acne therapies. We conducted a systematic review and network meta‐analysis to evaluate the efficacy of topical therapies for mild‐to‐moderate acne. Searches in PubMed/MEDLINE, Cochrane CENTRAL via Ovid, Embase via Ovid and Web of Science were conducted on 29 November 2021. Randomized controlled trials examining ≥12 weeks of topical treatments for acne vulgaris in subjects aged 12 and older were included. Main outcomes were absolute or percent change in acne lesion count and treatment success on the Investigator's Global Assessment scale. Thirty‐five randomized clinical trials with 33,472 participants comparing nine different topical agents were included. Adapalene‐benzoyl peroxide (BPO), clindamycin‐BPO and clindamycin‐tretinoin demonstrated the greatest reduction in non‐inflammatory (ratio of means [RoM] 1.76; 95% CI [1.46; 2.12], RoM 1.70; 95% CI [1.44; 2.02] and RoM 1.87; 95% CI [1.53; 2.30], respectively), inflammatory (RoM 1.56; 95% CI [1.44; 1.70], RoM 1.49; 95% CI [1.39; 1.60] and RoM 1.48; 95% CI [1.36; 1.61], respectively) and total lesion count (ROM 1.67; 95% CI [1.47; 1.90], RoM 1.59; 95% CI [1.42; 1.79] and RoM 1.64; 95% CI [1.42; 1.89], respectively) compared to placebo. All single agents outperformed placebo except tazarotene, which did not significantly outperform placebo for inflammatory and non‐inflammatory lesion count reduction. Most combination agents significantly outperformed their individual components in lesion count reduction and global assessment scores, except for clindamycin‐tretinoin and clindamycin‐BPO, which did not significantly outperform tretinoin (RoM 1.13; 95% CI [0.94; 1.36]) and BPO (RoM = 1.15, 95% CI [0.98; 1.36]), respectively, for non‐inflammatory lesion reduction. There was no significant difference amongst most single agents when evaluating lesion count reduction. Combination agents are generally most effective for mild‐to‐moderate acne; however for non‐inflammatory acne, the addition of clindamycin in topical regimens is unnecessary and should be avoided.

Monitoring of soil pollution with heavy metals using some microbiological parameters

ABSTRACT Although heavy metal pollution significantly impacts living organisms, the monitoring biomarkers can guide remediation. This study examined the response of Pb²⁺, Cd²⁺, Cu²⁺, Zn²⁺, Cr⁶⁺, Ni²⁺, and Hg²⁺ to soil microorganisms. Bacterial counts were measured at three metal concentrations (T₁, T₂, and T₃). Results revealed that Hg²⁺-T₁ caused a 91.4% reduction in bacterial counts within 10 days, while the other metals reduced counts by 32.9% to 71.8%. Higher concentrations (T₂ and T₃) of all metals, except Ni²⁺ (48.8%) at T₂, reduced counts by 92.1% to 99.6%. After 40 days, reductions were 74.5% for Hg²⁺-T₁, 97.0% for Cr6+-T2 , and 95.2 to 98.0 % for Hg2+, Cr6+, Cu2+ and Zn2+-T3 . Intrinsically resistant bacteria were observed after 40 days, constituting 34.2%–71.8% in T₁ of most metals, except Hg²⁺ (25.5%). These percentages decreased in T2 and T3 . 55.3% of the initial organic-N was oxidized after 20 days in untreated soil, while Pb²⁺ was the least toxic for ammonification, and Hg²⁺ was the highest. In untreated soil, 67.4% of ammoniacal-N was oxidized after 20 days. Nitrification was unaffected by T₁, except for Hg²⁺. At T₂, Hg²⁺, Ni²⁺, and Cd²⁺ were the most suppressive, while at T₃, Hg²⁺, Zn²⁺, and Cd²⁺ showed the most harmful effects.

Unveiling the Antianemic Activity, Physicochemical Aspects, Antioxidant Properties, and Mineral Profile of Petroselinum crispum L.

Anemia is a widespread global health concern necessitating effective, accessible, and natural interventions. The potential of medicinal plants to address anemia has garnered significant interest. Among these plants, parsley (Petroselinum crispum (Petroselinum crispum) L.) stands out as an edible and herbal-based option for combating anemia. Aim of the study: This study investigated the potential of P. crispum (PC-Ext) as an emerging antianemic product, focusing on its physicochemical attributes, antioxidant properties, and mineral profile. Both qualitative and quantitative analyses of the phenolic compounds in P. crispum were conducted by using high-performance liquid chromatography with a diode array detector (HPLC-DAD). Anemia was induced in rats by intravenous injections of phenylhydrazine, administered at a dose of 40 mg/kg for two consecutive days. The antianemic activity of PC-Ext was assessed at a dose of 500 mg/kg twice daily for 5 weeks by estimating blood parameters, such as serum iron and ferritin. Additionally, the osmotic fragility test measured the capacity of red blood cells to withstand osmotic shock of various concentrations of saline. Aqueous extract of P. crispum was rich in phytochemical compounds, including syringic acid, quercetin, catechin, gallic acid, and luteolin. The findings demonstrate the effectiveness of P. crispum in ameliorating phenylhydrazine-induced reductions in red blood cell count (RBCs), hemoglobin (Hb), and hematocrit (HCT) levels. Consequently, PC-Ext exhibits significant activity against phenylhydrazine-induced anemia in rats, as demonstrated by its ability to prevent hemolysis. Iron estimation within PC-Ext further confirms its utility in addressing both iron deficiency and ferritin-deficiency anemia. Therefore, PC exhibits a favorable effect against both types of anemia, iron deficiency, and hemolysis. The results of this study provide robust scientific validation for ethnomedicinal use and the potential utility of P. crispum, positioning it as a promising source for future pharmaceutical development.

Evaluation of Antimicrobial Efficacy of 5% Myristica Fragrans Mouthwash in Gingivitis Subjects - A Clinico Microbiological Study

Gingivitis is the inflammation or infection of gingiva that support the teeth. The prevailing belief regarding the cause for gingivitis is the toxins produced by the bacteria in the mouth, particularly the bacteria that causes the formation of plaque. Myristica fragrans commonly known as nutmeg possesses anti-carcinogenic, anti-inflammatory activities, antioxidant effect, anti-diabetic, and antibacterial properties. The seeds of nutmeg have the ability to inhibit the growth of Gram Negative and Positive bacteria. Objective: 1. To evaluate clinical parameters at baseline and 21 days post scaling after the use of Myristica fragrans mouthwash. 2. To evaluate the colony count of Porphyromonas gingivalis in plaque samples at baseline and 21 days after the use of Myristica fragrans mouthwash. Methodology: A total of 40 gingivitis subjects were selected and divided randomly into Group A and B. Group A, Non-surgical periodontal therapy followed by Myristica fragrans mouthwash (20) and Group B, Non-surgical periodontal therapy alone (20). The supragingival plaque samples were collected at baseline and 21 days after non surgical periodontal therapy. Results: Significant reduction in clinical parameters and colony count of Porphyromonas gingivalis after the use of 5% Myristica fragrans mouthwash.

A Literature Review: Relationship between Interleukin-1 Beta and the Severity of COVID-19

COVID-19 disease can cause dysregulation of the immune system, resulting in a cytokine storm. One of the cytokines released is IL-1B, a proinflammatory cytokine due to macrophage stimulation. This study aimed to provide a literature review of the value of Interleukin-1 beta (IL-1B) in patients with severity of COVID-19. This literature review was carried out using the search engines PubMed, Open Accessed Journal, Science Direct, and Google Scholar from December 2019 to December 2022. No studies suggested that IL-1B was associated with the severity of COVID-19. IL-1B is vital during the acute inflammatory response and helps T cells by linking innate and adaptive immunity as a lymphocyte activation factor. A gradual decrease in lymphocyte count was reported in severe COVID-19 diseases. The substantial reduction in lymphocyte count indicates that the SARS-CoV-2 virus increases immune cells and inhibits cellular immunity. This result might explain why IL-1B levels in mild COVID-19 were not significantly different from IL-1B levels in severe COVID-19. There was an increase in IL-1B levels in COVID-19 patients, but there was no relationship between IL-1B and the severity of COVID-19.

The small non-coding RNA Vaultrc5 is dispensable to mouse development.

Vault RNAs (vRNAs) are evolutionarily conserved small non-coding RNAs transcribed by RNA polymerase lll. Initially described as components of the vault particle, they have since also been described as noncanonical miRNA precursors and as riboregulators of autophagy. As central molecules in these processes, vRNAs have been attributed numerous biological roles including regulation of cell proliferation and survival, response to viral infections, drug resistance, and animal development. Yet, their impact to mammalian physiology remains largely unexplored. To study vault RNAs in vivo, we generated a mouse line with a conditional Vaultrc5 loss of function allele. Because Vaultrc5 is the sole murine vRNA, this allele enables the characterization of the physiological requirements of this conserved class of small regulatory RNAs in mammals. Using this strain, we show that mice constitutively null for Vaultrc5 are viable and histologically normal but have a slight reduction in platelet counts pointing to a potential role for vRNAs in hematopoiesis. This work paves the way for further in vivo characterizations of this abundant but mysterious RNA molecule. Specifically, it enables the study of the biological consequences of constitutive or lineage-specific Vaultrc5 deletion and of the physiological requirements for an intact Vaultrc5 during normal hematopoiesis or in response to cellular stresses such as oncogene expression, viral infection, or drug treatment.