Syphilis Treatment: Systematic Review and Meta-Analysis Investigating Nonpenicillin Therapeutic Strategies.

Background: Penicillin's long-standing role as the reference standard in syphilis treatment has led to global reliance. However, this dependence presents challenges, prompting the need for alternative strategies. We performed a systematic literature review and meta-analysis to evaluate the efficacy of these alternative treatments against nonneurological syphilis. Methods: We searched MEDLINE, the Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science from database inception to 28 August 2023, and we included studies that compared penicillin or amoxicillin monotherapy to other treatments for the management of nonneurological syphilis. Our primary outcome was serological cure rates. Random-effect models were used to obtain pooled mean differences, and heterogeneity was assessed using the I2 test. Results: Of 6478 screened studies, 27 met the inclusion criteria, summing 6710 patients. The studies were considerably homogeneous, and stratified analyses considering each alternative treatment separately revealed that penicillin monotherapy did not outperform ceftriaxone (pooled odds ratio, 1.66 [95% confidence interval, .97-2.84]; I2 = 0%), azithromycin (0.92; [.73-1.18]; I2 = 0%), or doxycycline (0.82 [.61-1.10]; I2 = 1%) monotherapies with respect to serological conversion. Conclusions: Alternative treatment strategies have serological cure rates equivalent to penicillin, potentially reducing global dependence on this antibiotic.

The effectiveness of the COVID-19 vaccines in the prevention of post-COVID conditions in children and adolescents: a systematic literature review and meta-analysis.

Objective: We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) in the pediatric population. Design: Systematic literature review/meta-analysis. Methods: We searched PubMed, Cumulative Index to Nursing and Allied Health Literature (CINAHL), EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to August 14, 2023, for studies evaluating the COVID-19 vaccine effectiveness against post-COVID conditions among vaccinated individuals < 21 years old who received at least 1 dose of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present 4 or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% CI) for post-COVID conditions between vaccinated and unvaccinated individuals. Results: Eight studies with 23,995 individuals evaluated the effect of vaccination on post-COVID conditions, of which 5 observational studies were included in the meta-analysis. The prevalence of children who did not receive COVID-19 vaccines ranged from 65% to 97%. The pooled prevalence of post-COVID conditions was 21.3% among those unvaccinated and 20.3% among those vaccinated at least once. The pooled DOR for post-COVID conditions among individuals vaccinated with at least 1 dose and those vaccinated with 2 doses were 1.07 (95% CI, 0.77-1.49) and 0.82 (95% CI, 0.63-1.08), respectively. Conclusions: A significant proportion of children and adolescents were unvaccinated, and the prevalence of post-COVID conditions was higher than reported in adults. While vaccination did not appear protective, conclusions were limited by the lack of randomized trials and selection bias inherent in observational studies.

Identification of Unique Fragmentation Patterns of Fentanyl Analog Protomers Using Structures for Lossless Ion Manipulations Ion Mobility-Orbitrap Mass Spectrometry.

The opioid crisis in the United States is being fueled by the rapid emergence of new fentanyl analogs and precursors that can elude traditional library-based screening methods, which require data from known reference compounds. Since reference compounds are unavailable for new fentanyl analogs, we examined if fentanyls (fentanyl + fentanyl analogs) could be identified in a reference-free manner using a combination of electrospray ionization (ESI), high-resolution ion mobility (IM) spectrometry, high-resolution mass spectrometry (MS), and higher-energy collision-induced dissociation (MS/MS). We analyzed a mixture containing nine fentanyls and W-15 (a structurally similar molecule) and found that the protonated forms of all fentanyls exhibited two baseline-separated IM distributions that produced different MS/MS patterns. Upon fragmentation, both IM distributions of all fentanyls produced two high intensity fragments, resulting from amine site cleavages. The higher mobility distributions of all fentanyls also produced several low intensity fragments, but surprisingly, these same fragments exhibited much greater intensities in the lower mobility distributions. This observation demonstrates that many fragments of fentanyls predominantly originate from one of two different gas-phase structures (suggestive of protomers). Furthermore, increasing the water concentration in the ESI solution increased the intensity of the lower mobility distribution relative to the higher mobility distribution, which further supports that fentanyls exist as two gas-phase protomers. Our observations on the IM and MS/MS properties of fentanyls can be exploited to positively differentiate fentanyls from other compounds without requiring reference libraries and will hopefully assist first responders and law enforcement in combating new and emerging fentanyls.

The effectiveness of COVID-19 vaccine in the prevention of post-COVID conditions: a systematic literature review and meta-analysis of the latest research.

Objective: We performed a systematic literature review and meta-analysis on the effectiveness of coronavirus disease 2019 (COVID-19) vaccination against post-COVID conditions (long COVID) among fully vaccinated individuals. Design: Systematic literature review/meta-analysis. Methods: We searched PubMed, Cumulative Index to Nursing and Allied Health, EMBASE, Cochrane Central Register of Controlled Trials, Scopus, and Web of Science from December 1, 2019, to June 2, 2023, for studies evaluating the COVID-19 vaccine effectiveness (VE) against post-COVID conditions among fully vaccinated individuals who received two doses of COVID-19 vaccine. A post-COVID condition was defined as any symptom that was present four or more weeks after COVID-19 infection. We calculated the pooled diagnostic odds ratio (DOR) (95% confidence interval) for post-COVID conditions between fully vaccinated and unvaccinated individuals. Vaccine effectiveness was estimated as 100% x (1-DOR). Results: Thirty-two studies with 775,931 individuals evaluated the effect of vaccination on post-COVID conditions, of which, twenty-four studies were included in the meta-analysis. The pooled DOR for post-COVID conditions among fully vaccinated individuals was 0.680 (95% CI: 0.523-0.885) with an estimated VE of 32.0% (11.5%-47.7%). Vaccine effectiveness was 36.9% (23.1%-48.2%) among those who received two doses of COVID-19 vaccine before COVID-19 infection and 68.7% (64.7%-72.2%) among those who received three doses before COVID-19 infection. The stratified analysis demonstrated no protection against post-COVID conditions among those who received COVID-19 vaccination after COVID-19 infection. Conclusions: Receiving a complete COVID-19 vaccination prior to contracting the virus resulted in a significant reduction in post-COVID conditions throughout the study period, including during the Omicron era. Vaccine effectiveness demonstrated an increase when supplementary doses were administered.

Urban Governance, Multisectoral Action, and Civic Engagement for Population Health, Wellbeing, and Equity in Urban Settings: A Systematic Review.

Objectives: To identify the validated and reliable indicators and tools to assess good governance for population health, wellbeing, and equity in urban settings, and assess processes of multisectoral action and civic engagement as reported by peer-reviewed articles. Methods: We conducted a systematic review searching six databases for observational studies reporting strategies of either urban health, multisectoral action or civic engagement for wellbeing, health, or equity. Results: Out of 8,154 studies initially identified we included 17. From the included studies, 14 presented information about high-income countries. The general population was the main target in most studies. Multisectoral action was the most frequently reported strategy (14 studies). Three studies used Urban Health Equity Assessment and Response Tool (Urban HEART). Health indicators were the most frequently represented (6 studies). Barriers and facilitators for the implementation of participatory health governance strategies were reported in 12 studies. Conclusion: Data on the implementation of participatory health governance strategies has been mainly reported in high-income countries. Updated and reliable data, measured repeatedly, is needed to closely monitor these processes and further develop indicators to assess their impact on population health, wellbeing, and equity.

Diagnostic Stewardship: A Systematic Review and Meta-analysis of Blood Collection Diversion Devices Used to Reduce Blood Culture Contamination and Improve the Accuracy of Diagnosis in Clinical Settings.

Background: Blood culture contamination may lead to misdiagnosis, overutilization of antibiotics, and prolonged length of stay. Blood specimen diversion devices can reduce contamination rates during blood culture collection procedures. We performed a systematic literature review and meta-analysis evaluating the influence of blood specimen diversion devices in blood culture contamination rates. Methods: We searched Medline, Cumulative Index to Nursing and Allied Health Literature, Embase, Cochrane, Scopus, and Web of Science, from database inception to 1 March 2023, for studies evaluating the impact of a diversion device on blood culture contamination. Blood culture contamination was a positive blood culture with microorganisms not representative of true bacteremia, but rather introduced during collection or processing the blood sample. Random-effects models were used to obtain pooled mean differences, and heterogeneity was assessed using the I2 test. Results: Of 1768 screened studies, 12 met inclusion criteria for this systematic literature review. Of them, 9 studies were included in the meta-analysis. Studies were substantially heterogeneous, but stratified analyses considering only high-quality studies revealed that venipuncture using a diversion device was associated with a significant reduction in blood culture contamination in comparison to the standard procedure of collection (pooled odds ratio [OR], 0.26 [95% confidence interval {CI}, .13-.54]; I2 = 19%). Furthermore, the stratified analysis showed that the adoption of a diversion device did not reduce the detection of true infection (pooled OR, 0.85 [95% CI, .65-1.11]; I2 = 0%). Conclusions: Blood culture diversion devices was associated with decreased contamination rates and could improve quality of care, reduce costs, and avoid unnecessary antibiotic use.

Design, delivery and effectiveness of health practitioner regulation systems: an integrative review.

BACKGROUND: Health practitioner regulation (HPR) systems are increasingly recognized as playing an important role in supporting health workforce availability, accessibility, quality, and sustainability, while promoting patient safety. This review aimed to identify evidence on the design, delivery and effectiveness of HPR to inform policy decisions. METHODS: We conducted an integrative analysis of literature published between 2010 and 2021. Fourteen databases were systematically searched, with data extracted and synthesized based on a modified Donabedian framework. FINDINGS: This large-scale review synthesized evidence from a range of academic (n = 410) and grey literature (n = 426) relevant to HPR. We identified key themes and findings for a series of HPR topics organized according to our structures-processes-outcomes conceptual framework. Governance reforms in HPR are shifting towards multi-profession regulators, enhanced accountability, and risk-based approaches; however, comparisons between HPR models were complicated by a lack of a standardized HPR typology. HPR can support government workforce strategies, despite persisting challenges in cross-border recognition of qualifications and portability of registration. Scope of practice reform adapted to modern health systems can improve access and quality. Alternatives to statutory registration for lower-risk health occupations can improve services and protect the public, while standardized evaluation frameworks can aid regulatory strengthening. Knowledge gaps remain around the outcomes and effectiveness of HPR processes, including continuing professional development models, national licensing examinations, accreditation of health practitioner education programs, mandatory reporting obligations, remediation programs, and statutory registration of traditional and complementary medicine practitioners. CONCLUSION: We identified key themes, issues, and evidence gaps valuable for governments, regulators, and health system leaders. We also identified evidence base limitations that warrant caution when interpreting and generalizing the results across jurisdictions and professions. Themes and findings reflect interests and concerns in high-income Anglophone countries where most literature originated. Most studies were descriptive, resulting in a low certainty of evidence. To inform regulatory design and reform, research funders and governments should prioritize evidence on regulatory outcomes, including innovative approaches we identified in our review. Additionally, a systematic approach is needed to track and evaluate the impact of regulatory interventions and innovations on achieving health workforce and health systems goals.

Expanded Coverage of Phytocompounds by Mass Spectrometry Imaging Using On-Tissue Chemical Derivatization by 4-APEBA.

Probing the entirety of any species metabolome is an analytical grand challenge, especially on a cellular scale. Matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) is a common spatial metabolomics assay, but this technique has limited molecular coverage for several reasons. To expand the application space of spatial metabolomics, we developed an on-tissue chemical derivatization (OTCD) workflow using 4-APEBA for the confident identification of several dozen elusive phytocompounds. Overall, this new OTCD method enabled the annotation of roughly 280 metabolites, with only a 10% overlap in metabolic coverage when compared to analog negative ion mode MALDI-MSI on serial sections. We demonstrate that 4-APEBA outperforms other derivatization agents by providing: (1) broad specificity toward carbonyls, (2) low background, and (3) introduction of bromine isotopes. Notably, the latter two attributes also facilitate more confidence in our bioinformatics for data processing. The workflow detailed here trailblazes a path toward spatial hormonomics within plant samples, enhancing the detection of carboxylates, aldehydes, and plausibly other carbonyls. As such, several phytohormones, which have various roles within stress responses and cellular communication, can now be spatially profiled, as demonstrated in poplar root and soybean root nodule.

Creating 'wellbeing societies': moving from rhetoric to action.

Several global challenges have emerged and coalesced in recent times, including climate change and environmental crises; growing health and social inequalities; geopolitical conflicts; and increasing rates of both communicable and noncommunicable and mental health diseases. The urgency and need for change has never been greater. In response, governments are paying increasing attention to the notion of wellbeing as an integrating concept to drive action to address these challenges. They are beginning to take action by introducing wellbeing indexes; wellbeing budgets; joined-up 'triple bottom line' approaches to policy making, and the inclusion of civil society in the decision-making processes. To date, these steps have been sporadic and localised; yet if these multiple social, environmental and economic crises are to be averted, coherent and systematic actions at the global, national and local levels are needed. The World Health Organization (WHO) and its 194 Member States have come together to map a path forward through the Geneva Charter for Well-being and the Well-being Framework. These aim to set the foundation and direction for action. They map the pathway towards a 'wellbeing society', a concept WHO brought to attention in the Geneva Charter. The intention is to support and galvanise nations to build on their nascent efforts to adopt a welbeing agenda, and move beyond rhetoric to take concerted action. To achieve the promise of 'wellbeing societies' will require developing new governance models,bringing all sectors together to define the problems and solutions, adopting new economic levers, and reorienting financing systems to focus on what is truly important. In this paper we describe the background and context for these initiatives, the concept of wellbeing societies and how WHO is advancing this global agenda.

Allosteric Inhibitors of Zika Virus NS2B-NS3 Protease Targeting Protease in "Super-Open" Conformation.

The Zika virus (ZIKV), a member of the Flaviviridae family, is considered a major health threat causing multiple cases of microcephaly in newborns and Guillain-Barré syndrome in adults. In this study, we targeted a transient, deep, and hydrophobic pocket of the "super-open" conformation of ZIKV NS2B-NS3 protease to overcome the limitations of the active site pocket. After virtual docking screening of approximately seven million compounds against the novel allosteric site, we selected the top six candidates and assessed them in enzymatic assays. Six candidates inhibited ZIKV NS2B-NS3 protease proteolytic activity at low micromolar concentrations. These six compounds, targeting the selected protease pocket conserved in ZIKV, serve as unique drug candidates and open new opportunities for possible treatment against several flavivirus infections.

Prevalence, predictors, and patient-reported outcomes of long COVID in hospitalized and non-hospitalized patients from the city of São Paulo, Brazil.

Background: Robust data comparing long COVID in hospitalized and non-hospitalized patients in middle-income countries are limited. Methods: A retrospective cohort study was conducted in Brazil, including hospitalized and non-hospitalized patients. Long COVID was diagnosed at 90-day follow-up using WHO criteria. Demographic and clinical information, including the depression screening scale (PHQ-2) at day 30, was compared between the groups. If the PHQ-2 score is 3 or greater, major depressive disorder is likely. Logistic regression analysis identified predictors and protective factors for long COVID. Results: A total of 291 hospitalized and 1,118 non-hospitalized patients with COVID-19 were included. The prevalence of long COVID was 47.1% and 49.5%, respectively. Multivariable logistic regression showed female sex (odds ratio [OR] = 4.50, 95% confidence interval (CI) 2.51-8.37), hypertension (OR = 2.90, 95% CI 1.52-5.69), PHQ-2 > 3 (OR = 6.50, 95% CI 1.68-33.4) and corticosteroid use during hospital stay (OR = 2.43, 95% CI 1.20-5.04) as predictors of long COVID in hospitalized patients, while female sex (OR = 2.52, 95% CI 1.95-3.27) and PHQ-2 > 3 (OR = 3.88, 95% CI 2.52-6.16) were predictors in non-hospitalized patients. Conclusion: Long COVID was prevalent in both groups. Positive depression screening at day 30 post-infection can predict long COVID. Early screening of depression helps health staff to identify patients at a higher risk of long COVID, allowing an early diagnosis of the condition.

Establishment of Hematological and Plasma Biochemical Reference Values and Analysis of Risk Factors for Pet Sugar Gliders (Petaurus breviceps) in Taiwan.

Hematological and plasma biochemical examination are crucial in the veterinary care of sugar gliders, which are increasingly popular in Taiwan and the United States. However, published research of the species' reference interval and related influencing factors were rare. The objectives of this study were to establish the hematological and plasma biochemical reference values for captive sugar gliders in Taiwan and to evaluate the influence of factors including age, gender, neuter status, location, season, diet, caging arrangement, and other pets in the household. A total of 42 clinically healthy pet sugar gliders were recruited. Morphometrical measurements and physiological data were collected, and hematological and plasma biochemical examinations were performed. The reference value of each index was calculated using Reference Value Advisor (RVA) software, following the American Society for Veterinary Clinical Pathology (ASVCP) guidelines. Normality of data distribution was tested, and data transformation was conducted. The parametric method and robust method were used to determine reference limits. Univariate analysis was performed, and multiple regression models were built for each hematological and plasma biochemical parameter. Red blood cell, hematocrit, and hemoglobin levels were higher in males, compared to females, while they were lower in the neutered group, compared to the intact group. Relative neutrophil counts were higher in elder sugar gliders, while relative lymphocyte counts were lower. Aspartate transaminase levels were higher in elder sugar gliders, while albumin levels were lower. Blood urea nitrogen levels were highest in spring. The blood profile and related effects presented in this study can provide useful information for veterinary care in pet sugar gliders.

Transcriptomic-Metabolomic Profiling in Mouse Lung Tissues Reveals Sex- and Strain-Based Differences.

Omics analyses are commonly used for identifying pathways and genes responsible for physiologic and pathologic processes. Though sex is considered a biological variable in rigorous assessments of pulmonary responses to oxidant exposures, the contribution of the murine strain is largely ignored. This study utilized an unbiased integrated assessment of high-resolution metabolomic profiling and RNA-sequencing to explore sex- and strain-dependent pathways in adult mouse lungs. The results indicated that strain exhibited a greater influence than sex on pathways associated with inflammatory and oxidant/antioxidant responses and that interaction metabolites more closely resembled those identified as differentially expressed by strain. Metabolite analyses revealed that the components of the glutathione antioxidant pathway were different between strains, specifically in the formation of mixed disulfides. Additionally, selenium metabolites such as selenohomocystiene and selenocystathionine were similarly differentially expressed. Transcriptomic analysis revealed similar findings, as evidenced by differences in glutathione peroxidase, peroxiredoxin, and the inflammatory transcription factors RelA and Jun. In summary, an multi-omics integrated approach identified that murine strain disproportionately impacts baseline expression of antioxidant systems in lung tissues. We speculate that strain-dependent differences contribute to discrepant pulmonary responses in preclincal mouse models, with deleterious effects on clinical translation.

Healthy cities initiative in China: Progress, challenges, and the way forward.

China implemented the first phase of its National Healthy Cities pilot program from 2016-20. Along with related urban health governmental initiatives, the program has helped put health on the agenda of local governments while raising public awareness. Healthy City actions taken at the municipal scale also prepared cities to deal with the COVID-19 pandemic. However, after intermittent trials spanning the past two decades, the Healthy Cities initiative in China has reached a crucial juncture. It risks becoming inconsequential given its overlap with other health promotion efforts, changing public health priorities in response to the pandemic, and the partial adoption of the Healthy Cities approach advanced by the World Health Organization (WHO). We recommend aligning the Healthy Cities initiative in China with strategic national and global level agendas such as Healthy China 2030 and the Sustainable Development Goals (SDGs) by providing an integrative governance framework to facilitate a coherent intersectoral program to systemically improve population health. Achieving this alignment will require leveraging the full spectrum of best practices in Healthy Cities actions and expanding assessment efforts. Funding: Tsinghua-Toyota Joint Research Fund "Healthy city systems for smart cities" program.