Infertility: A common target of antivaccine misinformation campaigns.

Misinformation, disinformation, and conspiracy theories about vaccines are key drivers of vaccine hesitancy. A repeated false claim about COVID-19 vaccines is that the vaccines cause female infertility. Dating back decades, various conspiracy theories have linked vaccination programs with infertility and thus harmed vaccination programs in Africa, Asia, and Central America, particularly against polio and tetanus. In the United States, Europe, and Australia, human papilloma virus (HPV) vaccines have been falsely blamed for infertility and primary ovarian insufficiency (POI). After distribution of COVID-19 vaccines began in December 2020, almost immediately there arose conspiracy theories claiming that these vaccines cause menstrual irregularities, miscarriages, and infertility, promoted by noted antivaccine activists Robert F. Kennedy, Jr. and Andrew Wakefield among others. Here we will explore the history of this antivaccine narrative, how it has been promulgated in the past and repurposed to COVID-19 vaccines, and strategies to counter it.

Updates in the treatment of asthma in pediatrics: A review for pharmacists.

PURPOSE: The purpose of this review is to summarize the management of asthma in children and to highlight different guideline-based approaches. This review also discusses literature regarding the use of corticosteroids, both inhaled and systemic, as well as biologic agents, in asthma management. SUMMARY: Asthma is a common chronic respiratory condition in the pediatric population and has evolved into a highly patient-specific disease. Of the 2 main asthma guidelines, one developed by the National Asthma Education and Prevention Program was recently published as a focused update in 2020. The other, from the Global Initiative for Asthma, focuses on a global strategy for management and prevention, with the most recent update in 2023. Both reports discuss diagnosis, assessment, and treatment of asthma in adults and children. Treatment is designed as a stepwise approach in both reports, although there are key differences. This article focuses on gaps in these guidelines, including the use of bronchodilators and inhaled corticosteroids with single maintenance and reliever therapy and long-acting muscarinic antagonists in children. It also reviews treatment in children under 5 years of age, although recommendations are limited due to a lack of evidence in this age group. Finally, this review discusses considerations for emerging treatments, including biologics, for patients who are difficult to treat. CONCLUSION: New treatment strategies and agents have emerged in the treatment of pediatric asthma. Pharmacists play a key role in providing education about, dispensing, and recommending the newest evidence-based treatment options for children.

Evidence for proton-pump inhibitor (PPI)-associated dysbiosis in metabolically unhealthy obesity.

Obesity adversely impacts millions of American adults by predisposing them to significant health risks and further complications. Obesity is differentiated into two groups: metabolically healthy and metabolically unhealthy. In contrast to metabolically healthy counterparts, obese individuals who are metabolically unhealthy display hallmark symptoms of metabolic syndrome (e.g., hypertension, dyslipidemia, hyperglycemia, abdominal obesity). Gastroesophageal reflux disease (GERD) commonly occurs in all obese populations, as do poor dietary habits. Proton-pump inhibitors (PPIs), due to their wide availability, are most often used to treat GERD-related heartburn and other symptoms. Here, we review the evidence on how poor diet as well as short- and long-term use of PPIs adversely affect the gastrointestinal microbiota to cause dysbiosis. Key components of dysbiosis-induced metabolically unhealthy obesity (MUO) associated with PPI use include "leaky gut," systemic low-grade inflammation, and reduced amounts of short-chain fatty acids (SCFAs) such as butyrate that promote metabolic health. The benefit of using probiotics to mitigate PPI-induced dysbiosis and MUO is also discussed.

Long COVID: Alice Evans, Brucellosis, and Reflections on Infectious Causes of Chronic Disease.

Despite more than a century of research on the link between infection and chronic diseases, we again find ourselves flummoxed by a new pathogen that causes long-term impairment. Patients have reported being ignored or minimized, resources are lacking for diagnosis and treatment, and frustrated individuals are turning outside of the scientific profession for answers. The experience mirrors that of American Society for Microbiology past president Alice C. Evans. Accidentally infected with Brucella melitensis during her laboratory research, Evans was chronically ill for more than 20 years, during which time friends, colleagues, and physicians cast doubt on her illness. As a result, she argued passionately for improved diagnostics and for those who reported chronic infection to be taken seriously rather than presumed to be "malingering" or using their illness for financial benefit. Lessons from Evans' experience are useful as we work toward understanding long COVID and patients suffering from the condition.

Incidental detection of malignancy on point-of-care renal ultrasound: A case series.

Renal point-of-care ultrasound (POCUS) is an increasingly common initial imaging modality in the diagnostic workup of renal colic. The primary use of renal POCUS is to assess for hydronephrosis; however, other significant findings suggestive of malignancy can also be identified. We present three cases of unexpected findings identified initially on POCUS in the emergency department, which subsequently led to new diagnoses of malignancy. As renal POCUS becomes more frequently used in clinical practice, physicians must be able to recognise abnormal images that indicate possible malignancy and the need for further workup.

Strengthening mental health research outcomes through genuine partnerships with young people with lived or living experience: A pilot evaluation study.

BACKGROUND: Despite increasing support for stakeholder inclusion in research, there is limited evaluative research to guide safe (i.e., youth-friendly) and meaningful (i.e., non-tokenistic) partnerships with young people with lived experience of mental ill-health in research. This paper describes a pilot evaluation and iterative design of a Youth Lived Experience Working Group (LEWG) protocol that was established by the Youth Mental Health and Technology team at The University of Sydney's Brain and Mind Centre, based on the results of two studies. METHODS: Study one consisted of a pilot evaluation of the extent to which youth partners felt empowered to contribute, to qualitatively explore how LEWG processes could be improved. Youth partners completed online surveys, and results were shared over two LEWG meetings in 2021 to empower youth partners to collectively identify actions of positive change regarding LEWG processes. These meetings were audio-recorded and transcripts were subsequently coded using thematic analysis. Study two assessed whether LEWG processes and proposed improvements were acceptable and feasible from the perspective of academic researchers via an online survey in 2022. RESULTS: Quantitative and qualitative data collected from nine youth partners and 42 academic researchers uncovered initial learnings regarding facilitators, motivators, and barriers to partnering with young people with lived experience in research. Implementing clear processes for youth partners and academic researchers on effective partnership strategies, providing training opportunities for youth partners to develop research skills, and providing regular updates on how youth partner contributions led to research outcomes were identified as key facilitators. CONCLUSIONS: This pilot study provides insight into a growing international field on how to optimise participatory processes so that researchers and young people with lived experience can be better supported and engaged to make meaningful contributions to mental health research. We argue that more transparency is needed around participatory research processes so that partnerships with young people with lived experience are not merely tokenistic. CONSUMER CONTRIBUTIONS: Our study has also been approved by and reflects the concepts and priorities of our youth lived experience partners and lived experience researchers, all of whom are authors of this paper.

Just DOAC: Use of direct-acting oral anticoagulants in pediatrics.

PURPOSE: The aim of this article is to provide an overview of the current literature for direct-acting oral anticoagulant (DOAC) use in pediatric patients and summarize ongoing trials. SUMMARY: In treatment of venous thromboembolism (VTE) in pediatric patients, evidence supports use of both dabigatran and rivaroxaban. Dabigatran has been shown to be noninferior to standard of care (SOC) in terms of efficacy, with similar bleeding rates. Similarly, treatment with rivaroxaban in children with acute VTE resulted in a low recurrence risk and reduced thrombotic burden, without increased risk of bleeding, compared to SOC. Treatment of pediatric cerebral venous thrombosis as well as central venous catheter-related VTE with rivaroxaban appeared to be both safe and efficacious and similar to that with SOC. Dabigatran also has a favorable safety profile for prevention of VTE, and rivaroxaban has a favorable safety profile for VTE prevention in children with congenital heart disease. Many studies with several different DOACs are ongoing to evaluate both safety and efficacy in unique patient populations, as well as VTE prevention. CONCLUSION: The literature regarding pediatric VTE treatment and prophylaxis is growing, but the need for evidence-based pediatric guidelines remains. Additional long-term, postauthorization studies are warranted to further elucidate safety and efficacy in clinical scenarios excluded in clinical trials. Additional data on safety, efficacy, and dosing strategies for reversal agents are also necessary, especially as the use of DOACs becomes more common in the pediatric population.

Family Communication Patterns and Parents' Intentions to Vaccinate Their Child Against COVID-19.

This study explored how family communication patterns relate to parental knowledge about COVID-19, vaccine confidence, and intentions to vaccinate their children. Parents from 4 states (Ohio, New York, Georgia, and Texas; n = 702) completed an online survey in March 2021. Results revealed that conversation orientation was positively associated with both COVID-19 knowledge and overall vaccine confidence, which were both positively associated with intentions to vaccinate one's child. The relationships between the 4 subscales of conformity and the outcome variables were mixed. We discuss the potential benefits of applying family communication patterns theory to complicated situations where parents are making health decisions for both themselves and their children.

Genetic characterization of Staphylococcus aureus isolated from Norway rats in Boston, Massachusetts.

BACKGROUND: Despite the importance of domesticated animals in the generation and transmission of antibiotic-resistant Staphylococcus aureus, the role of wild animals, specifically rodents, in the ecology of S. aureus remains unclear. We recovered and genotyped S. aureus isolates from wild Norway rats (Rattus norvegicus) in Boston, Massachusetts to examine genetic relationships between common human and animal S. aureus isolates in a large US metropolitan area. METHODS: We collected and necropsied 63 rats from June 2016 to June 2017. Nasal, foot pad, fur, and fecal swabs were collected. Staphylococcus aureus was isolated using culture-based methods and polymerase chain reaction confirmation. S. aureus isolates were spa typed, tested for antibiotic susceptibility, and whole genome sequenced. Assembled sequences were uploaded to the Comprehensive Antibiotic Resistance Database to identify antibiotic resistance elements. A phylogenetic tree was constructed using the neighbor-joining method with the maximum composite likelihood distance in MEGA7. RESULTS: We recovered 164 Gram-positive bacterial isolates from Norway rats. Nineteen isolates from eight individual rats were confirmed as S. aureus (prevalence: 12.9% (8/63)). All S. aureus isolates were methicillin-susceptible S. aureus (MSSA), pvl-negative, and resistant to penicillin. Two isolates displayed resistance to erythromycin. Four different S. aureus spa types were detected (t933, t10751, t18202, and t189). Thirteen unique antibiotic resistance elements were identified, and all isolates shared genes mepR, mgrA, arlR, and S. aureus norA. Phylogenetic analysis if the 19 S. aureus isolates revealed they were genetically similar to four clades of S. aureus with similar resistance gene profiles isolated from both human- and animal-derived S. aureus, as well as formed a distinct phylogenetic cluster composed only of rat isolates. CONCLUSIONS: Wild rodents may serve as a reservoir or vector of antibiotic resistance genes in the urban environment with relevance for human and animal health.

A Social Cognitive Theory Approach to Understanding Parental Attitudes and Intentions to Vaccinate Children during the COVID-19 Pandemic.

The distribution of the COVID-19 vaccine represents a path towards global health after a worldwide pandemic. Yet, the U.S. response to the vaccination rollout has been politically polarized. The aim of this paper is to contribute to the understanding of the contextual factors that influence parents' attitudes towards health officials and their intention to vaccinate children, focusing on communication behaviors, personal factors, and geographic locations. We use Bandura's triadic reciprocal determinism (TRD) model which posits reciprocal influence between personal factors, environmental factors, and behaviors. We found that personal factors (having younger children and identifying as Republican partisans), and the behavioral factor of conservative news use were significantly related to more negative attitudes towards health officials and lower vaccination intentions. Conversely, Democrats and liberal news use were significantly related to warmer attitudes and greater vaccination intentions. The environmental factor of geographic location across four states with different partisan dynamics was not significantly related to attitudes and behavioral intentions. Results from a post-hoc analysis show that news media use and partisanship were the strongest correlates of parents' attitudes towards health officials. This evidence points to the politicization of the COVID-19 vaccine being a key consideration regarding vaccine uptake.

Fieldwork for public health responses during pandemics: lessons from the New South Wales Health experience with COVID-19.

Problem: Fieldwork is a vital component of public health emergency response, yet little has been published on undertaking fieldwork safely. Safety is of particular importance with emerging pandemic viruses, which can pose additional risks to public health fieldwork staff. Context: During a pandemic, surge health staff may be drawn from diverse professional backgrounds; they may have limited experience in fieldwork or be unfamiliar with the risks posed by a novel virus. Novel pathogens pose dangers to fieldwork staff, particularly when there are global or local shortages of personal protective equipment. Action: During the coronavirus disease 2019 (COVID-19) pandemic, New South Wales (NSW) Health's Public Health Emergency Operations Centre (PHEOC) deployed staff for fieldwork in a range of settings. The PHEOC developed a protocol to systematize planning, risk assessment and management for COVID-19 fieldwork. The protocol was accompanied by training, discussion exercises and debriefs to support PHEOC fieldwork staff. Lessons learned: Effective fieldwork is an essential component of outbreak investigation and management, including stakeholder management. Here, we share and discuss key elements of the NSW Health protocol to support fieldwork during outbreak responses for emerging communicable diseases across various resource contexts. Limited understanding of novel viruses, particularly in the early phases of a pandemic, must be considered in decisions to deploy fieldwork staff and implement precautionary risk mitigation approaches. Planning is essential to protect staff and ensure ethical allocation of resources. Through appropriate selection of teams and training, surge staff can be supported to effectively conduct fieldwork.

Pharmacokinetics, Mass Balance, Excretion, and Tissue Distribution of Plasmalogen Precursor PPI-1011.

PPI-1011 is a synthetic plasmalogen precursor in development as a treatment for multiple plasmalogen-deficiency disorders. Previous work has demonstrated the ability of PPI-1011 to augment plasmalogens and its effects in vitro and in vivo, however, the precise uptake and distribution across tissues in vivo has not been investigated. The purpose of this study was to evaluate the pharmacokinetics, mass balance, and excretion of [14C]PPI-1011 following a single oral administration at 100 mg/kg in Sprague-Dawley rats. Further tissue distribution was examined using quantitative whole-body autoradiography after both single and repeat daily doses at 100 mg/kg/day. Non-compartmental analysis showed that following a single dose, PPI-1011 exhibited peak levels between 6 and 12 h but also a long half-life with mean t1/2 of 40 h. Mass balance showed that over 50% of the compound-associated radioactivity was absorbed by the body, while approximately 40% was excreted in the feces, 2.5% in the urine, and 10% in expired air within the first 24 h. Quantitative whole-body autoradiography following a single dose showed uptake to nearly all tissues, with the greatest initial uptake in the intestines, liver, and adipose tissue, which decreased time-dependently throughout 168 h post-dose. Following 15 consecutive daily doses, uptake was significantly higher across the entire body at 24 h compared to single dose and remained high out to 96 h where 75% of the initially-absorbed compound-associated radioactivity was still present. The adipose tissue remained particularly high, suggesting a possible reserve of either plasmalogens or alkyl diacylglycerols that the body can pull from for plasmalogen biosynthesis. Uptake to the brain was also definitively confirmed, proving PPI-1011's ability to cross the blood-brain barrier. In conclusion, our results suggest that oral administration of PPI-1011 results in high uptake across the body, and that repeated dosing over time represents a viable therapeutic strategy for treating plasmalogen deficiencies.

Novel γ-sarcoglycan interactors in murine muscle membranes.

BACKGROUND: The sarcoglycan complex (SC) is part of a network that links the striated muscle cytoskeleton to the basal lamina across the sarcolemma. The SC coordinates changes in phosphorylation and Ca++-flux during mechanical deformation, and these processes are disrupted with loss-of-function mutations in gamma-sarcoglycan (Sgcg) that cause Limb girdle muscular dystrophy 2C/R5. METHODS: To gain insight into how the SC mediates mechano-signaling in muscle, we utilized LC-MS/MS proteomics of SC-associated proteins in immunoprecipitates from enriched sarcolemmal fractions. Criteria for inclusion were co-immunoprecipitation with anti-Sgcg from C57BL/6 control muscle and under-representation in parallel experiments with Sgcg-null muscle and with non-specific IgG. Validation of interaction was performed in co-expression experiments in human RH30 rhabdomyosarcoma cells. RESULTS: We identified 19 candidates as direct or indirect interactors for Sgcg, including the other 3 SC proteins. Novel potential interactors included protein-phosphatase-1-catalytic-subunit-beta (Ppp1cb, PP1b) and Na+-K+-Cl--co-transporter NKCC1 (SLC12A2). NKCC1 co-localized with Sgcg after co-expression in human RH30 rhabdomyosarcoma cells, and its cytosolic domains depleted Sgcg from cell lysates upon immunoprecipitation and co-localized with Sgcg after detergent permeabilization. NKCC1 localized in proximity to the dystrophin complex at costameres in vivo. Bumetanide inhibition of NKCC1 cotransporter activity in isolated muscles reduced SC-dependent, strain-induced increases in phosphorylation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). In silico analysis suggests that candidate SC interactors may cross-talk with survival signaling pathways, including p53, estrogen receptor, and TRIM25. CONCLUSIONS: Results support that NKCC1 is a new SC-associated signaling protein. Moreover, the identities of other candidate SC interactors suggest ways by which the SC and NKCC1, along with other Sgcg interactors such as the membrane-cytoskeleton linker archvillin, may regulate kinase- and Ca++-mediated survival signaling in skeletal muscle.

When measles came to class: a look back at the 1989 Kent State University measles epidemic.

BACKGROUND: Measles was eliminated from the United States in 2000, following a change from a single dose of measles vaccine to two doses after an epidemic 1989-1991. Several college campuses experienced outbreaks, including Kent State University (KSU) in Ohio. METHODS: Local news media from 1988 to 1989 were searched in August 2019. Interventions taken by the university were recorded, and an epidemic curve constructed. RESULTS: The first measles cases were reported in October 1988. The outbreak diminished over winter break. New cases were confirmed in February 1989. Infected students were instructed to vacate the dorms. Vaccines were mandated for student groups. The epidemic grew rapidly in March but slowed after spring break. By April, 380 cases had been reported and 7000 students vaccinated. CONCLUSIONS: KSU was one of the hardest-hit universities during the 1989 measles epidemic. A combination of vaccination, isolation, quarantine, and elimination of public events helped to curtail the epidemic.

Genetic epidemiology approach to estimating birth incidence and current disease prevalence for rhizomelic chondrodysplasia punctata.

BACKGROUND: Rhizomelic chondrodysplasia punctata (RCDP) is an inherited ultra-rare disease which results in severely impaired physical and mental development. Mutations in one of five genes involved in plasmalogen biosynthesis have been reported to drive disease pathology. Estimates of disease incidence have been extremely challenging due to the rarity of the disorder, preventing an understanding of the unmet medical need. To address this, we have prepared a disease incidence and prevalence model based on genetic epidemiology approaches to estimate the total number of RCDP patients affected, and their demographic characteristics. RESULTS: Extraction of allelic frequencies for known and predicted pathogenic variants in PEX7, GNPAT, AGPS, FAR1, PEX5 (limited to the PTS2 domain encoding region) genes, from large-scale human genetic diversity datasets (TopMed and gnomAD) revealed the mutational landscape contributing to the RCDP patient population in the US and Europe. We computed genetic prevalence to derive birth incidence for RCDP and modeled the impact to life expectancy to obtain high confidence estimates of disease prevalence. Our population genetics-based model indicates PEX7 variants are expected to contribute to the majority of RCDP cases in both the US and Europe; closely aligning with clinical reports. Furthermore, this model provides estimates for RCDP subtypes due to mutations in other genes, including exceedingly rare subtypes. CONCLUSION: In total, the estimated number of RCDP patients in the US and the five largest European countries (UK, Germany, France, Italy and Spain) is between 516 and 847 patients, all under the age of 35 years old. This model provides a quantitative framework for better understanding the unmet medical need in RCDP, to help guide disease awareness and diagnosis efforts for this specific patient group.

Broadly neutralizing HIV-1 antibody reactivity in HIV tests: implications for diagnostics.

OBJECTIVE: Passive immunization with broadly neutralizing antibodies (bNAbs) is under evaluation for HIV prevention. BNAbs target gp120 or gp41, two HIV envelope antigens commonly present in diagnostic tests. Depending on bNAb type and dose administered to humans, serum levels can reach nearly 1 mg/ml and wane over several weeks to months. We investigated the reactivity of bNAbs in HIV serological tests to inform diagnostic testing practices for persons treated with these products. DESIGN AND METHODS: The antigp120 bNAbs VRCO1, PGT121, PGT145, 3BNC117, 10-1074 and N6 and antigp41 bNAbs 10E8 and 10E8v4 were tested with the laboratory-based Bio-Rad Ag/Ab Combo assay, the point-of-care single-use Determine Combo, OraQuick, Reveal G4, SureCheck, Uni-Gold, INSTI and DPP HIV-1/2 assays, and the supplemental Geenius and HIV-1 Western Blot assays. RESULTS: At 1 mg/ml, all bNAbs were nonreactive in four screening tests. OraQuick, SureCheck, Reveal G4 and INSTI detected at least two bNAbs each; SureCheck exhibited reactivity to six bNAbs. Geenius was HIV-1 indeterminate (gp160+) with all bNAbs except PGT121, which was HIV antibody-negative. HIV-1 Western Blot was indeterminate (gp41+/gp160+) with 10E8 and 10E8v4 and negative with the remaining bNAbs. There was no correlation between the test antigen construct(s) and bNAb reactivity. CONCLUSION: We identified a laboratory-based Ag/Ab EIA and three single-use rapid HIV tests that are nonreactive against a panel of bNAbs supporting some diagnostic tests can distinguish HIV-1 infection events among persons receiving bNAb immunoprophylaxis. Evaluation of HIV diagnostic tests prior to clinical use may identify suitable serologic assays for persons administered bNAbs.

COVID-19 Vaccine Acceptance: We Need to Start Now.

In this perspective, we discuss the importance of developing a vaccine to help curb transmission of severe acute respiratory syndrome coronavirus 2. The question remains: Once a safe and effective vaccine is developed, will the public be willing to get it? We present information from one of the first tracking polls to assess public attitudes and perceptions toward a possible coronavirus disease 2019 vaccine that suggests public hesitancy over a potential vaccine, concern regarding accelerating clinical trials, and unease over the vaccine approval process. Public health experts, government officials, advocates, and others in the scientific community should respect the signals of hesitancy and communicate sensitivity, applying lessons not only to how we message, but also in how we build this urgently needed vaccine if we are to have successful uptake once available.

Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Transmission Dynamics Should Inform Policy.

It is generally agreed that striking a balance between resuming economic and social activities and keeping the effective reproductive number (R0) below 1 using nonpharmaceutical interventions is an important goal until and even after effective vaccines become available. Therefore, the need remains to understand how the virus is transmitted in order to identify high-risk environments and activities that disproportionately contribute to its spread so that effective preventative measures could be put in place. Contact tracing and household studies, in particular, provide robust evidence about the parameters of transmission. In this Viewpoint, we discuss the available evidence from large-scale, well-conducted contact-tracing studies from across the world and argue that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission dynamics should inform policy decisions about mitigation strategies for targeted interventions according to the needs of the society by directing attention to the settings, activities, and socioeconomic factors associated with the highest risks of transmission.

Multisystem Inflammatory Syndrome in Children.

BACKGROUND: As the number of coronavirus disease 2019 (COVID-19) cases increases globally, more cases of a rare COVID-19-associated disease process are being identified in the pediatric population. This syndrome is referred to as multisystem inflammatory syndrome in children (MIS-C). Clinical manifestations of the syndrome vary and include one or a combination of the following: vasodilatory shock, cardiogenic shock, Kawasaki-like disease, cytokine storming, coronary artery dilatation, and aneurysms. CASE REPORT: This case report describes the presentation, findings, workup, and treatment for a 9-year-old boy diagnosed with MIS-C. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: It is important to recognize MIS-C, as it shares many of the same features as other disease processes, for example, Kawasaki disease and toxic shock syndrome, but has different complications if left untreated.