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Objective: To evaluate the role of ethanolic extract of Myristica fragrans in morphine dependence. Methods: Wistar albino rats were made moderate and severe grade morphine dependence by administering morphine sulphate in dose of 10 mg /kg (i.p.), twice daily for 4 days and by increasing doses of 10-100 mg/kg (i.p.), twice daily for 7 days, respectively. The signs of spontaneous abstinence syndrome were recorded 12 hours in both studies after the last dose of morphine for 30 minutes and quantified by 'counted' and 'checked' signs. Ethanolic extract of Myristica fragrans (EEMF) was administered p.o. in different regimen: (a) EEMF 200 mg/kg along with morphine twice daily for 4 days and 7 days in moderately and severely induced morphine dependence group, respectively. (b) EEMF 400 mg/kg (p.o.), single dose10 hours after the last dose of morphine in both moderately and severely induced morphine dependence rats. Result: Oral administration of EEMF in both study groups caused significant reduction in the scores of counted and checked signs of morphine abstinence syndrome as compared to active morphine control group. The reduction was significantly more in regimen 'a' as compared to regimen 'b'. Conclusion: Ethanolic extract of Myristica fragrans seed significantly reduced the mean scores of various'counted signs' and 'checked signs' of morphine withdrawal syndrome and might give a solution as a substitute therapy in morphine de-addiction. [ABSTRACT FROM AUTHOR]

PurposeTo assess the long-term safety and efficacy of intravitreal triamcinolone acetonide injection in the management of macular oedema caused by central, hemi-, and branch retinal vein occlusion (CRVO, HRVO, or BRVO).MethodsThis prospective, interventional case series included 13 patients (13 eyes) with retinal vein occlusion and macular oedema. They received an intravitreal injection of 4 mg triamcinolone acetonide. Follow-up was for 1 year with repeat injections where appropriate. Outcome measures were visual acuity and macular thickness measured using ocular coherence tomography (OCT).ResultsThere were four patients with CRVO, one with HRVO, and eight with BRVO (13 eyes). Mean duration of symptoms before intravitreal triamcinolone acetonide injection was 6.8 months (SD 4.5 months). Eight eyes (62%) responded well with improved visual acuity and macular thickness 1–3 months postinjection. All eight eyes developed recurrent macular oedema and five received repeat injections. Three patients declined a second injection. No improvement in visual acuity or OCT macular thickness was seen after the second injection with visual acuity returning to baseline levels at 1-year follow-up. Three eyes (23%) showed no response to the initial injection (no improvement in macular thickness or visual acuity). Seven patients (54%) had a rise in intraocular pressure with six (46%) requiring treatment.ConclusionsIntravitreal injection of triamcinolone acetonide is effective as a short-term treatment of macular oedema owing to retinal vein occlusion, improving both visual acuity and macular thickness. However, this effectiveness is not maintained after 1 year despite repeat injections.Eye (2008) 22, 60–64; doi:10.1038/sj.eye.6702518; published online 11 August 2006 [ABSTRACT FROM AUTHOR]

Methicillin-resistant Staphylococcus aureus (MRSA) was recovered many times from raw poultry meat or carcasses; however, these were predominantly humanassociated strains. Hence, possible human involvement in contamination of carcasses by slaughterhouse workers and other human handlers may not be overlooked in such cases. During this study, efforts were focused on isolation of MRSA from oropharynx of live poultry. Samples were collected from oropharynx of 50 live cockerels. A total of 25 Staphylococcus aureus isolates were identified. Only four isolates produced glistening, convex and mucoid colonies of MRSA on selective media. These isolates were further confirmed for methicillin resistance through latex agglutination test and produced catalase and coagulase, β-hemolysis on blood agar. Out of 25 Staphylococcus aureus isolates, 16% isolates were identified as MRSA. Antibiotic susceptibility profile of MRSA isolates indicated 100% sensitivity against vancomycin and linezolid whereas 100% resistance was recorded against oxacillin, cefoxitin and penicillin. However, 50% of the MRSA isolates were sensitive to levofloxacin and trimethoprim/ sulphamethoxazole and 25% isolates displayed resistance to tetracycline. [ABSTRACT FROM AUTHOR]

Background: The heme oxygenase (HO) system plays a significant role in neuroprotection and reduction of neuroinflammation and neurodegeneration. The system, via isoforms HO-1 and HO-2, regulates cellular redox balance. HO-1, an antioxidant defense enzyme, is highlighted due to its association with depression, characterized by heightened neuroinflammation and impaired oxidative stress responses., Methodology: We observed the pathophysiology of HO-1 and phytochemicals as its modulator. We explored Science Direct, Scopus, and PubMed for a comprehensive literature review. Bibliometric and temporal trend analysis were done using VOSviewer., Results: Several phytochemicals can potentially alleviate neuroinflammation and oxidative stress-induced depressive symptoms. These effects result from inhibiting the MAPK and NK-κB pathways - both implicated in the overproduction of pro-inflammatory factors - and from the upregulation of HO-1 expression mediated by Nrf2. Bibliometric and temporal trend analysis further validates these associations., Conclusion: In summary, our findings suggest that antidepressant agents can mitigate neuroinflammation and depressive disorder pathogenesis via the upregulation of HO-1 expression. These agents suppress pro-inflammatory mediators and depressive-like symptoms, demonstrating that HO-1 plays a significant role in the neuroinflammatory process and the development of depression., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier GmbH. All rights reserved.)

The COVID-19 pandemic has amplified preexisting challenges for educators as manifested in high rates of work-related stress and burnout, and educators leaving the profession in higher numbers than ever before. In this article, we highlight the urgency for work-related well-being supports for educators, with a particular focus on system changes. Individual self-care is necessary, yet insufficient. To this end, we recommend the use of a multitiered system of support framework to promote a supportive and balanced work environment for all educators, tailored to local needs. We provide a rationale for the use of a tiered model and give specific recommendations for implementation and sustainability of a continuum of supports for school-wide educator well-being. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Introduction: Endothelial dysfunction has been implicated in various cardiovascular disorders as the initial pathology. Allopurinol has been shown to improve endothelial dysfunction in patients with gout, but its effect on cardiovascular patients is unclear., Aims: We aim to assess allopurinol efficacy in improving endothelial dysfunction overall and in different disease states including but not limited to heart failure, chronic kidney disease, ischemic heart disease METHODS: We conducted a literature search of PubMed, Cochrane's Central Library, and Scopus until December 2022, including randomized controlled trials and double-arm observational studies. The primary outcome measure was endothelial function assessed by change in flow mediated dilation (FMD) RESULTS: Our meta-analysis included 22 studies with a total of 1472 patients. Our pooled analysis shows that allopurinol significantly improved FMD (WMD = 1.46%, 95% CI [0.70, 2.22], p < 0.01) compared to control. However, there was no significant difference between allopurinol and control for endothelial-independent vasodilation measured by forearm blood flow (WMD = 0.10%, 95% CI [- 0.89, 0.69], p = 0.80). Subgroup analysis indicated that the effect of allopurinol on FMD was more significant in diabetic and congestive heart failure patients., Conclusion: While allopurinol may improve endothelial function in various patient populations, further high-quality randomized controlled trials are needed to determine its efficacy in preventing cardiovascular disease exacerbation., (© 2023. Italian Society of Hypertension.)

Alternative approaches and/or modified approaches to tackle resistance in gut microbes are need of the hour. The current study was planned to find the resistance modulation and toxicity potential of sodium alginate stabilized MgO nanoparticles and antibiotics against Escherichia coli ( E. coli ) isolated from the gut of Houbara bustard bird ( n = 105 fecal samples). The preparations consisted of gel stabilized ampicillin (G+A), gel stabilized MgO and ampicillin (G+M+A), gel stabilized MgO and cefoxitin (G+M+C), gel stabilized tylosin (G+T), gel stabilized MgO and tylosin (G+M+T), and gel stabilized MgO (M+G). The fecal samples showed 53% (56/105) prevalence of E. coli which was found to be significantly ( p < 0.05) associated with most of the assumed factors and resistant to multiple drugs. G+M+T showed the lowest (4.883 ± 0.00 μ g/mL) minimum inhibitory concentration (MIC) followed G+M+C, G+M+A, G+A, M+G, and G+T. Significant reduction ( p < 0.05) in MIC with respect to incubation interval found at the 16 th hr for G+M+A, G+A, and G+M+C that further remained nonsignificant ( p > 0.05) onwards until the 24 th hr of incubation. In the case of G+T and M+G, significant reduction in MIC was found at the 20 th hr and 24 th hr of incubation. Ecotoxicology and histopathology trials on snails showed mild changes in MICs of the preparations. The study thus concluded increasing drug resistance in E . coli of houbara bird while sodium alginate stabilized MgO nanoparticles and antibiotics were effective alternative antibacterial composites with mild toxicity., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2022 Afshan Muneer et al.)

This study was designed to compare immunopathological effects of in ovo vaccination with post-hatch vaccination against IBD in White Leghorn chicks. A total of 189 embryonated eggs were divided into six groups. At day 18 of incubation, groups A-C were administered in ovo with 228E, Winterfield 2512:10/3 and 2512/90:10/2.7, respectively, group D (post-hatch vaccination) and group E as shamed control (for quality evaluation of in ovo vaccination technique), and group F as control. The results showed that antibody titers against IBD detected by ELISA on days 2, 17, and 28 were significantly higher in all in ovo groups as compared to control groups E and F. On day 17, all vaccinated groups ( in ovo and post-hatch vaccinated) showed no significant differences in antibody titers among themselves; however, at day 28, only the post-hatch group showed significantly higher antibody titers followed by in ovo vaccinated groups. The cell-mediated immunity determined by PHA-P assay was significantly higher in all vaccinated groups than the non-vaccinated groups. No clinical signs of IBD infection were observed in any of the vaccinated groups. There was only increase in bursa size of groups vaccinated with intermediate plus strains (groups A, C, and D) at day 28. The histopathology showed that all the treatment groups had mild lesions induced by IBD virus in bursa. This study concluded that in ovo vaccination with live IBD vaccines provides protective immunity to the chickens even in the presence of IBD-specific MDA; therefore, the onset of immunity was much earlier than the post-hatch vaccination and in ovo groups also maintained protective immunity against IBD for longer time., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Zaheer, Chen, Khan, Elokil, Saleemi, Zaheer and Khan.)

Current experiment was planned to investigate the deleterious effects of the graded doses of aflatoxin B1 (AFB1) on white leghorn male birds. For this purpose, one-hundred birds of 8 weeks of age were divided into 4 equal groups and reared on feed contaminated with different doses of AFB1 for 10 weeks. Group A was kept as a control group and was fed with normal toxin-free diet; groups B, C, and D were offered feed containing 100 ppb, 200 ppb, and 400 ppb of AFB1, respectively. The birds were euthanized at the 4th and 10th week of the experiment. Clinical signs, behavioral changes, absolute and relative organ weight of the testes, and sperm motility were measured. Cellular immune response was observed through carbon clearance assay (CCA), P-HAP, and antibody response against sheep red blood cells (SRBC). Results showed a dose-dependent decline in the immune response of birds with the increase in the level of AFB1 in the feed. A significant decrease in the serum levels of testosterone, prolactin, and LH were observed at the end of the study. Grossly, testicular size and volume were reduced in ABF1 fed birds, while histological examination showed moderate to severe necrosis of testicular parenchyma, with partial to complete arrest of spermatogenesis. Very few spermatozoa were found in group C, while they were almost absent in group D which was offered a diet containing 400 ppb AFB1. The motility of sperms was reduced in all treated groups except control. The abovementioned results showed that AFB1 had severe toxic effects on the reproductive and immunological parameters of WLH male birds in a dose-dependent manner., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Poor solubility is the major challenge involved in the formulation development of new chemical entities (NCEs), as more than 40% of NCEs are practically insoluble in water. Solid dispersion (SD) is a promising technology for improving dissolution and, thereby, the bioavailability of poorly soluble drugs. This study investigates the influence of a pH-sensitive acrylate polymer, EPO, on the physicochemical properties of rosuvastatin calcium, an antihyperlipidemic drug. In silico docking was conducted with numerous polymers to predict drug polymer miscibility. The screened-out polymer was used to fabricate the binary SD of RoC in variable ratios using the co-grinding and solvent evaporation methods. The prepared formulations were assessed for physiochemical parameters such as saturation solubility, drug content and in vitro drug release. The optimized formulations were further ruled out using solid-state characterization (FTIR, DSC, XRD and SEM) and in vitro cytotoxicity. The results revealed that all SDs profoundly increased solubility as well as drug release. However, the formulation RSE-2, with a remarkable 71.88-fold increase in solubility, presented 92% of drug release in the initial 5 min. The molecular interaction studied using FTIR, XRD, DSC and SEM analysis evidenced the improvement of in vitro dissolution. The enhancement in solubility of RoC may be important for the modulation of the dyslipidemia response. Therefore, pharmacodynamic activity was conducted for optimized formulations. Our findings suggested an ameliorative effect of RSE-2 in dyslipidemia and its associated complications. Moreover, RSE-2 exhibited nonexistence of cytotoxicity against human liver cell lines. Convincingly, this study demonstrates that SD of RoC can be successfully fabricated by EPO, and have all the characteristics that are favourable for superior dissolution and better therapeutic response to the drug.

Porphyromonas gingivalis, a prominent pathogen responsible for acute periodontal diseases, is widely studied by the scientific community for its successful evasion of the host immune system. P. gingivalis is associated with rheumatoid arthritis, dementia, and Alzheimer's. The pathogen successfully survives itself against the heavy load of conventional antibiotics because of its ability to evade the host immune system. Subtractive proteomics and reverse vaccinology approaches were employed in order to prioritize the best proteins for vaccine designing. Three vaccine candidates with Uniprot ID: Q7MWZ2 (histidine Kinase), Q7MVL1 (Fe (2+) transporter), and Q7MWZ2 (Capsular polysaccharide transport protein) were identified for vaccine designing. These proteins are antigenic and essential for pathogen survival. A wide range of immunoinformatics tools was applied for the prediction of epitopes, B, and T cells, for the vaccine candidate proteins. Molecular docking of the predicted epitopes against the MHC molecules were carried out. In-silico vaccine was constructed using carefully evaluated epitopes and consequently modeled for docking with human Toll-like receptor 2. Chain C of Pam3CSK4 (PDB ID; 2Z7X) was linked to the vaccine as an adjuvant to boost immune response towards the vaccine. For stability evaluation of the vaccine-TLR-2 docked complex, Molecular Dynamics simulations were performed. The reverse-translated nucleotide sequence cloned in Eschericia coli to attain the maximal expression of the vaccine protein. The maximal expression was ensured by CAI score of 0.96. The current vaccine requires future experimental validation to confirm its effectiveness. The vaccine developed will be helpful to protect against P. gingivalis associated infections.Communicated by Ramaswamy H. Sarma.

Nanomaterials have wide-ranging biomedical applications in prevention, treatment and control of diseases. Nanoparticle based vaccines have proven prodigious prophylaxis of various infectious and non-infectious diseases of human and animal concern. Nano-vaccines outnumber the conventional vaccines by virtue of plasticity in physio-chemical properties and ease of administration. The efficacy of nano-based vaccines may be attributed to the improved antigen stability, minimum immuno-toxicity, sustained release, enhanced immunogenicity and the flexibility of physical features of nanoparticles. Based on these, the nano-based vaccines have potential to evoke both cellular and humoral immune responses. Targeted and highly specific immunological pathways required for solid and long lasting immunity may be achieved with specially engineered nano-vaccines. This review presents an insight into the prevention of infectious diseases (of bacterial, viral and parasitic origin) and non-infectious diseases (cancer, auto-immune diseases) using nano-vaccinology. Additionally, key challenges to the effective utilization of nano-vaccines from bench to clinical settings have been highlighted as research domains for future., Competing Interests: There is no conflict of interest amongst the author for publishing this exclusive review., (© 2020 Elsevier Ltd. All rights reserved.)

Inclusion body hepatitis (IBH), hydropericardium syndrome, and gizzard erosion associated with fowl adenovirus (FAdV) infections are reported globally and resulted in significant poultry industry economic losses. In 2018, severe IBH appeared in Pakistan in a 17-week-old layer flock. Subsequently, a FAdV-11 strain (designated as PKFAd18) was isolated from liver samples and identified based on phylogenetic analyses of the serotype-specific L1 region of the capsid hexon gene. There is no complete genome sequence of the Pakistani FAdV-11. This study successfully sequenced the complete genome of PKFAd18. The full genome of PKFAd18 contains 43 840 base pairs (bp) with a G + C content of 53.9 %, which is comparable to other FAdV serotypes. Similar to other FAdV-11 strains, PKFAd18 has only one fiber, while FAdV-1 and FAdV-4 have two fibers. Notably, PKFAd18 showed unique characteristics compared to other FAdV-11 strains. A natural large genomic deletion (1215 bp) appeared in tandem repeat region two, relative to the ON-NP2 strain. Phylogenetic analyses of the PKFAd18 penton gene showed higher homology with FAdV-9, highlighting potential natural recombination between FAdV-11 and FAdV-9. Moreover, the pathogenicity of PKFAd18 studied in specific-pathogen-free chickens showed that PKFAd18 is capable of inducing severe IBH and could be responsible for IBH in Pakistan. Thus, the first complete genome of FAdV-11 in Pakistan was sequenced in this study, which enriches the diversity of knowledge about FAdV-11 and is useful for developing diagnostics and vaccines for IBH induced by FAdV-11 in Pakistan., Competing Interests: Declarations of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Aim: To compare effectiveness, safety, and cost of photodynamic therapy (PDT) and radiofrequency ablation (RFA) in treatment of Barrett's dysplasia (BD)., Methods: Consecutive case series of patients undergoing either PDT or RFA treatment at single center by a single investigator were compared. Thirty-three patients with high-grade dysplasia (HGD) had treatment with porfimer sodium photosensitzer and 630 nm laser (130 J/cm), with maximum of 3 treatment sessions. Fifty-three patients with BD (47 with low-grade dysplasia -LGD, 6 with HGD) had step-wise circumferential and focal ablation using the HALO system with maximum of 4 treatment sessions. Both groups received proton pump inhibitors twice daily. Endoscopic biopsies were acquired at 2 and 12 mo after enrollment, with 4-quadrant biopsies every 1 cm of the original BE extent. A complete histological resolution response of BD (CR-D) was defined as all biopsies at the last endoscopy session negative for BD. Fisher's exact test was used to assess differences between the two study groups for primary outcomes. For all outcomes, a two-sided P value of less than 0.05 was considered to indicate statistical significance., Results: Thirty (91%) PDT patients and 39 (74%) RFA were men (P = 0.05). The mean age was 70.7 ± 12.2 and 65.4 ± 12.7 (P = 0.10) year and mean length of BE was 5.4 ± 3.2 cm and 5.7 ± 3.2 cm (P = 0.53) for PDT and RFA patients, respectively. The CR-D was (18/33) 54.5% with PDT vs (47/53) 88.7% with RFA (P = 0.001). One patient with PDT had an esophageal perforation and was managed with non-surgical measures and no perforation was seen with RFA. PDT was five times more costly than RFA at our institution. The two groups were not randomized and had different BD grading are the limitations of the study., Conclusion: In our experience, RFA had higher rate of CR-D without any serious adverse events and was less costly than PDT for endoscopic treatment of BD.

Objective: This study examines factors that predict elevated direct costs of pediatric patients with type 1 diabetes., Methods: A cohort of 784 children with type 1 diabetes at least 6 months postdiagnosis and managed by pediatric endocrinologists at Texas Children's Hospital were included in this study. Actual reimbursed costs from January 2004 to December 2005 were obtained. Medication and supply costs were based on estimates from insulin dosage and type of insulin regimen prescribed, respectively. We examined utilization of care, total diabetes-related direct medical costs, and predictors of direct costs and hospitalization., Results: Annually, 7% (58/784) of patients (excluding initial hospitalization at diagnosis) had a diabetes-related hospitalization and median length of stay was days. Mean total diabetes-related direct cost per person-year was $4730 [95% confidence interval (CI), 4516-4944]. Supplies accounted for 38% and medications 33% of costs, respectively. Older age, hemoglobin A(1C) (HbA(1C) ) > 8.5%, use of a multi-injection or pump regimen, living in a non-married household, and female gender were associated with higher annual costs. HbA(1C) > 8.5%, living in a non-married household, and female gender increased the odds of a diabetes-related hospitalization., Discussion: Better metabolic control in patients with type 1 diabetes was associated with lower direct medical costs and lower odds of hospitalization. Marital status of the primary caregiver, irrespective of type of insurance, impacts the patient's healthcare costs and risk of hospitalization. This large single-center US study analyzes cost distribution in children with diabetes and is informative for payers and providers focused on effective management and improving healthcare costs., (© 2010 John Wiley & Sons A/S.)

The abundant expression of tumor necrosis factor (TNF) is a hallmark of chronic inflammation of the gastrointestinal tract. Prolonged inflammation can lead to inflammatory bowel disease. TNF biosynthesis is regulated both at transcription and posttranscriptional levels. However, the stimulation-induced increase in translation rate is much larger. This might indicate the possibility of a posttranscriptional regulatory mechanism. How, during basal conditions, is the free concentration of TNF tightly regulated at low levels? The stability and translational efficiency of TNF transcript are regulated by an AU-rich element (ARE) in the 3'-UTR of messenger RNA. A transacting protein, TTP, binds to ARE and enhances the mRNA turnover. Here, we examine a proposal that TNF homeostasis is regulated by a TTP-TNF interaction loop at the posttranscriptional level. We propose a computational framework of this regulatory loop by modeling the role of AREs in mediating the messenger RNA stability and translation. This posttranscriptional regulatory loop between TTP and TNF is composed of two feedback loops (i.e. positive and negative). The mutual interaction of these feedback loops regulates the biosynthesis response of TNF during basal and inflammatory conditions. Here, we also propose an explanation for why the p38 inhibitors become insensitive for TTP knock-out mice.

Approaches to the artificial impoundment and theoretical design of sedimentation retention basin are reviewed with particular attention to best management practice (BMP) to control agriculture and surface runoff. Sediments retention basins are the small version of farm pond used where a criteria of farm pond is not met. Such basin traps the pollutants and suspended solids prior to entry into streams and lakes. The study is focused with special reference to the assessment and control of non-point source pollution (NPSP) from the sub-basin area of Tai Lake in the Xishan County of Wuxi City of China. The author suggested two different approaches to conduct this study including theoretical design for sedimentation retention basin and computation of flow, sediment transport and deposition during the artificial impoundment of retention basin for BMP's utilization. Theoretical design will provide a useful function as a first line defense against the movement of sediments and transport of pollutants into the Tai Lake while the assessment of sediments deposition will help to make its proper use and periodic cleanup.