Safety and efficacy of antibiotics compared with appendicectomy for treatment of uncomplicated acute appendicitis: meta-analysis of randomised controlled trials

Objective To compare the safety and efficacy of antibiotic treatment versus appendicectomy for the primary treatment of uncomplicated acute appendicitis. Design Meta-analysis of randomised controlled trials. Population Randomised controlled trials of adult patients presenting with uncomplicated acute appendicitis, diagnosed by haematological and radiological investigations. Interventions Antibiotic treatment versus appendicectomy. Outcome measures The primary outcome measure was complications. The secondary outcome measures were efficacy of treatment, length of stay, and incidence of complicated appendicitis and readmissions. Results Four randomised controlled trials with a total of 900 patients (470 antibiotic treatment, 430 appendicectomy) met the inclusion criteria. Antibiotic treatment was associated with a 63% (277/438) success rate at one year. Meta-analysis of complications showed a relative risk reduction of 31% for antibiotic treatment compared with appendicectomy (risk ratio (Mantel-Haenszel, fixed) 0.69 (95% confidence interval 0.54 to 0.89); I2=0%; P=0.004). A secondary analysis, excluding the study with crossover of patients between the two interventions after randomisation, showed a significant relative risk reduction of 39% for antibiotic therapy (risk ratio 0.61 (0.40 to 0.92); I2=0%; P=0.02). Of the 65 (20%) patients who had appendicectomy after readmission, nine had perforated appendicitis and four had gangrenous appendicitis. No significant differences were seen for treatment efficacy, length of stay, or risk of developing complicated appendicitis. Conclusion Antibiotics are both effective and safe as primary treatment for patients with uncomplicated acute appendicitis. Initial antibiotic treatment merits consideration as a primary treatment option for early uncomplicated appendicitis

Oxygen Generation from Carbon Dioxide for Advanced Life Support

The partial electrochemical reduction of carbon dioxide (CO2) using ceramic oxygen generators (COGs) is well known and widely studied. However, complete reduction of metabolically produced CO2 (into carbon and oxygen) has the potential of reducing oxygen storage weight for life support if the oxygen can be recovered. Recently, the University of Florida devel- oped novel ceramic oxygen generators employing a bilayer elec- trolyte of gadolinia-doped ceria and erbia-stabilized bismuth ox- ide (ESB) for NASA's future exploration of Mars. The results showed that oxygen could be reliably produced from CO2 at temperatures as low as 400 C. The strategy discussed here for advanced life support systems employs a catalytic layer com- bined with a COG cell so that CO2 is reduced all the way to solid carbon and oxygen without carbon buildup on the COG cell and subsequent deactivation

The Efficacy of Interventions Aimed at Reducing Early Childhood Toxic Stress: A Systematic Review and Meta-Analysis

The foundations of mental health and well-being are built in the first five years of life. Early childhood toxic stress (i.e., repeated, excessive, or prolonged activation of the body’s stress response systems) can undermine children’s sense of safety, sense of stability, and ability to form healthy relationships. The damaging effects of toxic stress can disrupt the normal course of brain, immune, and metabolic development, placing children at increased risk for mental and physical health problems that can last into adulthood. Counselors are uniquely qualified to help prevent and treat early childhood toxic stress. Yet, gaps between counseling theory, research, and practice hamper progress towards this goal. In this systematic review and meta-analysis, I aim to bridge the gaps using the following strategic aims to identify effective interventions: 1) focus on the critical/sensitive period of development occurring during the birth to five period; 2) leverage developmental science spanning biological, socioecological, and psychological frameworks; and 3) advance health equity work

INCREASING BEGINNING TEACHER EFFICACY & RETENTION IN A DIVERSE MIDDLE SCHOOL SETTING WITH APPROPRIATE PROFESSIONAL LEARNING

Teacher retention, particularly among beginning educators, remains a pressing concern in education, especially in Title I middle schools that serve diverse student populations. High teacher attrition rates negatively impact student achievement, school culture, and overall educational equity. This study examines the role of targeted professional learning in increasing beginning teacher efficacy and retention in a rural North Carolina middle school. Through an exploratory sequential mixed methods approach, qualitative data were collected through interviews, classroom observations, and instructional rounds, followed by quantitative analysis utilizing pre- and post-surveys to measure changes in teacher confidence and instructional effectiveness. The findings reveal that relevant, structured, and ongoing professional learning opportunities significantly enhance teacher efficacy by providing educators with the tools and strategies necessary to navigate the challenges of their early careers. Key themes that emerged from the study include the importance of classroom management training, content-specific instructional strategies, culturally responsive pedagogy, and mentorship programs. Teachers who received professional learning tailored to their individual needs reported increased confidence in their instructional delivery, greater job satisfaction, and a stronger sense of belonging within the school community. Additionally, opportunities for collaboration, reflection, and leadership development played a pivotal role in sustaining teacher engagement and reducing burnout. Despite its contributions, this study acknowledges certain limitations, including the relatively small sample size and its focus on a single school setting. However, the findings offer meaningful insights into the design and implementation of effective professional learning programs that can support beginning teachers in similar educational contexts. Future research should explore the long-term impact of professional learning on teacher retention rates across multiple school districts and investigate its direct correlation to student achievement. By prioritizing intentional, sustained, and responsive professional development, school leaders can foster a culture of continuous learning, ultimately improving both teacher retention and student outcomes

Phase variation mediates reductions in expression of surface proteins during persistent meningococcal carriage

Asymptomatic and persistent colonization of the upper respiratory tract by Neisseria meningitidis occurs despite elicitation of adaptive immune responses against surface antigens. A putative mechanism for facilitating host persistence of this bacterial commensal and pathogen is alterations in expression of surface antigens by simple sequence repeat (SSR)-mediated phase variation. We investigated how often phase variation occurs during persistent carriage by analyzing the SSRs of eight loci in multiple isolates from 21 carriers representative of 1 to 6 months carriage. Alterations in repeat number were detected by a GeneScan analysis and occurred at 0.06 mutations/gene/month of carriage. The expression states were determined by Western blotting and two genes, fetA and nadA, exhibited trends toward low expression states. A critical finding from our unique examination of combinatorial expression states, “phasotypes,” was for significant reductions in expression of multiple phase-variable surface proteins during persistent carriage of some strains. The immune responses in these carriers were examined by measuring variant-specific PorA IgG antibodies, capsular group Y IgG antibodies and serum bactericidal activity in concomitant serum samples. Persistent carriage was associated with high levels of specific IgG antibodies and serum bactericidal activity while recent strain acquisition correlated with a significant induction of antibodies. We conclude that phase-variable genes are driven into lower expression states during long-term persistent meningococcal carriage, in part due to continuous exposure to antibody-mediated selection, suggesting localized hypermutation has evolved to facilitate host persistence

The Cognitive Ageing, Nutrition and Neurogenesis trial: Design and progress

Introduction: Cohort studies indicate that long-chain n-3 polyunsaturated fatty acids and flavonoids may improve cognition and reduce dementia risk. The neuroprotective effects of these dietary components indicate that they are likely to be additive and potentially synergistic. Methods: The Cognitive Ageing, Nutrition and Neurogenesis trial hypothesizes that an intervention comprising long-chain n-3 polyunsaturated fatty acids (docosahexaenoic acid and eicosapentaenoic acid) and cocoa flavan-3-ols (n-3 FLAV) will mitigate the cognitive decline anticipated to naturally occur over 1 year in older adults with mild cognitive impairment or subjective memory impairment. A double-blinded, placebo-controlled parallel design is used. Two hundred fifty-nine adults (aged ≥55 years) with mild cognitive impairment or subjective memory impairment were recruited and randomized to a control or n-3 FLAV group (1.5 g docosahexaenoic acid + eicosapentaenoic acid and 500 mg n-3 FLAV daily) for 12 months. Cognitive performance was measured three times over the 1-year intervention, at 0 (baseline), 3, and 12 months. The primary end point is hippocampus-sensitive cognitive function (e.g., number of false-positives on the Picture Recognition Task of the Cognitive Drug Research test battery). Secondary outcomes include additional cognitive measures, brain atrophy and blood flow (assessed by magnetic resonance imaging), vascular function, circulating biomarkers of cardiovascular and cognitive health, gut microflora speciation and metabolism, red blood cell fatty acid status, and urine flavan-3-ol metabolites. The intervention arms were matched for sex and apolipoprotein E4 status to allow retrospective exploratory analysis of the impact of these variables on response to intervention.  Results: Screening began in 2015, with all baseline visits completed in March 2017. The intervention was finished in March 2018.  Discussion: Cognitive Ageing, Nutrition and Neurogenesis aims to identify an effective diet-based intervention to prevent or delay cognitive impairment in cognitively at-risk individuals, which could ultimately contribute to a reduced population burden of dementia

Skeletal Muscle Atrophy in Chronic Kidney Disease (CKD)

Background:   Skeletal muscle atrophy and dysfunction occur with chronic kidney disease (CKD) progression leading to morbidity, mortality, and falls. Skeletal muscle dysfunction may be due to impaired fatty acid (FA) oxidation and enhanced pyruvate oxidation as demonstrated in preliminary metabolomic data. We performed multiple techniques to assess the extent of muscle dysfunction and associated pathways, including: systematic review and meta-analysis,  assays of disease progression and FA metabolism, expression of markers associated with skeletal muscle FA metabolism and pyruvate oxidation.     Methods:   Meta-analysis: Multiple databases were used to identify relevant studies of muscle atrophy in preclinical and clinical models.   Experimental Study: 1)CKD rats and 2)Normal littermates (N=12/gr) at 35 weeks. Extensor digitorum longus (EDL) and soleus were harvested at sacrifice. Serum Biochemistry: Plasma BUN, calcium and phosphorus were analyzed using colorimetric assays. Carnitine Assay: Plasma carnitine levels was measured using ELISA kit. Protein Expression: Western blots with the lysate of EDL and soleus to determine the activity levels of PDH and PDK4.    Results:    A total of 4685 studies were screened in the meta-analysis, of which 646 were relevant. Subsequent steps are to perform full text review and data extraction. Animal studies: BUN and phosphorus were significantly increased in CKD compared to normal. Carnitine levels were significantly decreased in CKD rats compared to normal. PDH was not significantly different in the EDL or soleus. PDK4 is yet to be performed.     Conclusions:   The extent to which muscle atrophy occurs will be identified in the meta-analysis. Elevated BUN confirmed disease and carnitine assay confirmed low carnitine levels in CKD. Identifying low carnitine has led to an interventional study of carnitine supplementation to determine if there was improved FA oxidation. Testing of PDK4 is needed to determine significance of pyruvate regulation. Reviewing the literature and understanding the mechanism of skeletal muscle atrophy in CKD will allow future targeted therapeutics.&nbsp