Evaluating the Heart Wise Exercise™ program: a model for safe community exercise programming.

BACKGROUND: Greater availability of community exercise facilities is recommended to promote physical activity in the large number of people with chronic disease. The Heart Wise Exercise (HWE) program encourages existing community-based exercise facilities to build capacity to serve such patients, by working with interested facilities to ensure they meet safety criteria, and educating exercise leaders. METHODS: Using a piloted checklist, 45 HWE programs were audited for the six HWE criteria (outlined below) in the greater Ottawa and Toronto areas of Ontario, Canada. A survey was also administered to a convenience sample of HWE program participants (N = 127). RESULTS: Criteria 1: 71% of leaders encouraged daily aerobic exercise; participants reported engaging in 194 min/week of aerobic exercise. Criteria 2: 100% of programs incorporated a warm-up and cool-down, and 84% encouraged self-monitoring during class. Criteria 3: 98% of programs offered options for participants to exercise at their appropriate intensity. Criteria 4: HWE participants reported having chronic conditions including arthritis (41%), osteoporosis (26%) diabetes (8%), heart disease (6%) and chronic obstructive pulmonary disease (6%). Criteria 5: 93% of instructors offered health screening for participants. Criteria 6: 100% of sites had automated external defibrillators, and 90% of the instructors were aware of the documented emergency plan. The exercise leaders reported being 'knowledgeable/comfortable/confident' in providing exercise guidance to, and having clients with chronic health conditions; directing clients to other services; offering exercise intensity options; helping clients listen to their bodies; and, encouraging clients to provide information regarding their health. The participants reported being, on average, 'somewhat happy' to 'very happy' with HWE locations; program dates and times; leaders' knowledge of disease and exercise; exercise intensity; cost; and, social aspect. CONCLUSIONS: HWE programs are safe and appropriate for persons with varying chronic health conditions, and participants are satisfied with and will likely continue attending their HWE classes. Future efforts should be directed at increasing awareness of HWE programs among referring healthcare professionals and participants at risk of chronic conditions. The HWE training program should emphasize that HWE leaders regularly encourage self-monitoring and daily aerobic exercise, which is well-known to reduce the burden of many chronic diseases.

Phenotypic characterization of HAM1, a novel mating regulator of the fungal pathogen Cryptococcus neoformans.

Cryptococcus neoformans is a fungal pathogen responsible for >200,000 yearly cases with a mortality as high as 81%. This burden results, in part, from an incomplete understanding of its pathogenesis and ineffective antifungal treatments; hence, there is a pressing need to understand the biology and host interactions of this yeast to develop improved treatments. Protein palmitoylation is important for cryptococcal virulence, and we previously identified the substrates of its main palmitoyl transferase. One of them was encoded by the uncharacterized gene CNAG_02129. In the filamentous fungus Neurospora crassa, a homolog of this gene named hyphal anastomosis protein 13 plays a role in proper cellular communication and filament fusion. In Cryptococcus, cellular communication is essential during mating; therefore, we hypothesized that CNAG_02129, which we named hyphal anastomosis protein 1 (HAM1), may play a role in mating. We found that ham1Δ mutants produce more fusion products during mating, filament more robustly, and exhibit competitive fitness defects under mating and non-mating conditions. Additionally, we found several differences with the major virulence factor, the polysaccharide capsule, that may affect virulence, consistent with prior studies linking virulence to mating. We observed that ham1Δ mutants have decreased capsule attachment and transfer but exhibit higher amounts of exopolysaccharide shedding and biofilm production. Finally, HAM1 expression is significantly lower in mating media relative to non-mating conditions, consistent with it acting as a negative regulator of mating. Understanding the connection between mating and virulence in C. neoformans may open new avenues of investigation into ways to improve the treatment of this disease. IMPORTANCE: Fungal mating is a vital part of the lifecycle of the pathogenic yeast Cryptococcus neoformans. More than just ensuring the propagation of the species, mating allows for sexual reproduction to occur and generates genetic diversity as well as infectious propagules that can invade mammalian hosts. Despite its importance in the biology of this pathogen, we still do not know all of the major players regulating the mating process and if they are involved or impact its pathogenesis. Here, we identified a novel negative regulator of mating that also affects certain cellular characteristics known to be important for virulence. This gene, which we call HAM1, is widely conserved across the cryptococcal family as well as in many pathogenic fungal species. This study will open new avenues of exploration regarding the function of uncharacterized but conserved genes in a variety of pathogenic fungal species and specifically in serotype A of C. neoformans.

Phenotypic characterization of HAM1, a novel mating regulator of the fungal pathogen Cryptococcus neoformans.

Cryptococcus neoformans is a fungal pathogen responsible for >200,000 yearly cases with a mortality as high as 81%. This burden results, in part, from an incomplete understanding of its pathogenesis and ineffective antifungal treatments; hence, there is a pressing need to understand the biology and host interactions of this yeast to develop improved treatments. Protein palmitoylation is important for cryptococcal virulence, and we previously identified the substrates of its main palmitoyl transferase. One of them was encoded by the uncharacterized gene CNAG_02129. In the filamentous fungus Neurospora crassa, a homolog of this gene named HAM-13 plays a role in proper cellular communication and filament fusion. In Cryptococcus, cellular communication is essential during mating, therefore we hypothesized that CNAG_02129, which we named HAM1, may play a role in mating. We found that ham1Δ mutants produce more fusion products during mating, filament more robustly, and exhibit competitive fitness defects under mating and non-mating conditions. Additionally, we found several differences with the major virulence factor, the polysaccharide capsule, that may affect virulence, consistent with prior studies linking virulence to mating. We observed that ham1Δ mutants have decreased capsule attachment and transfer but exhibit higher amounts of exopolysaccharide shedding and biofilm production. Lastly, HAM1 expression is significantly lower in mating media relative to non-mating conditions, consistent with it acting as a negative regulator of mating. Understanding the connection between mating and virulence in C. neoformans may open new avenues of investigation into ways to improve the treatment of this disease.

Real-world effectiveness of recombinant zoster vaccine in self-identified Chinese individuals aged ≥50 years in the United States.

We evaluated the vaccine effectiveness (VE) of two doses of recombinant zoster vaccine (RZV) against herpes zoster (HZ) and postherpetic neuralgia (PHN) in Chinese adults at Kaiser Permanente Southern California (KPSC). Chinese KPSC members were identified based on self-reported ethnicity or self-reported preferred spoken/written language. Those aged ≥50 years who received two doses of RZV 4 weeks to ≤ 6 months apart were matched 1:4 to RZV unvaccinated Chinese members and followed through June 2022; second doses were accrued 6/1/2018-12/31/2020. We estimated incidence and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) comparing outcomes (HZ and PHN). Adjusted VE (%) was calculated as (1-aHR)×100. 3978 RZV vaccinated Chinese members were matched to 15,912 RZV unvaccinated Chinese members. The incidence per 1000 person-years (95% CI) of HZ in the vaccinated group was 1.5 (0.9-2.5) and 10.9 (9.8-12.1) in the unvaccinated group; aHR (95% CI) was 0.12 (0.07-0.21). Adjusted VE (95% CI) was 87.6% (78.9-92.7) against HZ. We identified 0 PHN cases in the vaccinated group and 19 in the unvaccinated group. Among Chinese adults aged ≥50 years, two doses of RZV provided substantial protection against HZ and PHN supporting the real-world effectiveness of the vaccine in this population.

Wastewater surveillance facilitates climate change-resilient pathogen monitoring.

Traditional disease surveillance systems are ill-equipped to handle climate change-driven shifts in pathogen dynamics. If paired with wastewater surveillance, a cost-effective and scalable approach for generating high-resolution health data, such next-generation systems can enable effective resource allocation and delivery of targeted interventions.

Effectiveness and safety of recombinant zoster vaccine: A review of real-world evidence.

The recombinant zoster vaccine (RZV) was licensed in the US for prevention of herpes zoster (HZ) in 2017. We conducted a literature search (January 1, 2017-August 1, 2023) using PubMed, Embase, and Scopus to consolidate the real-world evidence related to RZV. Overall, RZV effectiveness against HZ was high across the studied populations in real-world settings, including adults aged ≥ 50 years and patients aged ≥ 18 years with immunodeficiency or immunosuppression. Effectiveness was higher with two doses versus one dose, especially in elderly people and immunocompromised individuals. The safety profile of RZV was broadly consistent with that established in clinical trials. RZV does not appear to increase the risk of disease flares in patients with immune-mediated diseases. Approximately two-thirds of individuals received a second RZV dose within 2-6 months after the first dose. Collectively, RZV effectiveness against HZ was high, and these real-world studies reaffirm its favorable benefit-risk profile.

What is the context?Herpes zoster is a common and painful rash that develops following reactivation of latent (meaning silent or dormant) varicella zoster virus, which is the virus that causes the common childhood illness chickenpox. The recombinant zoster vaccine (RZV) was first approved for the prevention of herpes zoster in the USA and Canada in 2017 and has since been approved in the European Union and various other countries. The approval was based on the results of large clinical trials. Since its launch over 5 years ago, evidence for RZV use in real-world settings has been collected; the benefits of real-world studies include large sample sizes, more diverse populations, and the ability to identify rare side effects.What is new?We provide a review of real-world studies, which have shown that RZV is effective across the studied populations, including in adults aged 50 years and above and in patients with immunodeficiencies (i.e., those who have a decreased ability to fight infections or other diseases) or receiving immunosuppressive therapies (treatments that lower the activity of the body's immune system). The safety profile of RZV in real-world studies was generally consistent with that seen in clinical trials.What is the impact?These studies show the effectiveness and well-tolerated safety profile of RZV in real-world settings.

Impact of applying different resting blood pressure cut-points to clear for maximal exercise.

OBJECTIVE: The purpose of this study was to examine the impact of applying six commonly-used and two proposed resting blood pressure (BP) cut-points to clear individuals for maximal exercise in non-clinical health, wellness, commercial fitness agencies and physically demanding occupation test sites. METHODS: Participants (n = 1670) completed the Physical Activity Readiness Questionnaire for Everyone (PAR-Q+) and had their resting BP measured. Individuals with a BP >160/90 mmHg were further screened for contraindications to exercise using the ePARMed-X+ (www.eparmedx.com), all 1670 were cleared. There were no adverse events during or post exercise. RESULTS: The percentages of participants cleared for each BP cut-point were: <130/80 mmHg (85.3%), <140/90 mmHg (93.4%), <144/90 mmHg (94.6%), <144/94 mmHg (96.3%), <150/100 mmHg (98.6%), <160/90 mmHg (95.6%), <160/94 mmHg (97.8%) and <160/100 mmHg (99.5%). Individuals who would not have been cleared without further screening were significantly older, had a higher BMI, or had a lower maximal oxygen consumption. CONCLUSIONS: Conservative or lower resting BP cut-points currently applied to clear individuals for maximal exercise provide an unnecessary barrier. For individuals categorized as low-to- moderate risk by evidence-based screening tools such as the PAR-Q+ and ePARmed-X+, we recommend a resting BP cut-point of <160/94 mmHg to clear for maximal exercise until sufficient evidence is amassed to support the increase to <160/100 mmHg.

Potential of Membranes Surrounding the Fetus as Immunoprotective Cell-Carriers for Allogeneic Transplantations.

BACKGROUND: Membranes surrounding the fetus play a crucial role in providing a physical and immunological barrier between a semiallogeneic fetus and mother during pregnancy. In this study, we tested whether cotransplantation of fetal membranes (FMs) and allogeneic donor cells would improve the retention and function of allografts in mice. METHODS: Intact and enzyme-digested membranes obtained from E18-E19 pregnant mice were subcutaneously cotransplanted with 10F7MN hybridoma cells that are of BALB/cByJ (Balb) origin and secrete anti-human CD235a antibody. Cells were transplanted into C57BL/6J (B6, allogeneic), Balb (syngeneic), and FVB/NJ (third-party) mice. Serum was collected after 1 and 3 weeks of cell transplantation and tested using flow cytometry for the presence of anti-human CD235a antibody. Immunosuppressive functions of membranes were further investigated by analyzing the cytokine profile of supernatants collected from allo-reactive mixed lymphocyte reactions (MLRs) using a multiplex cytokine assay. RESULTS: B6 mice transplanted with 10F7MN cells along with membranes syngeneic to the host had significantly higher levels of CD235a antibody when compared to B6 mice that received cells without membranes, allogenic membranes, or third-party membranes. Syngeneic membranes significantly inhibited T-cell proliferation in the presence of allogeneic stimuli and suppressed the release of Th1-cytokines such as IFNγ, TNFα, and IL-2 in MLRs. Additionally, increases in the levels of Th2-cytokines were found in MLRs containing membrane-derived cells. CONCLUSIONS: Our study highlights the potential use of syngeneic FMs to act as potent cell-carriers that could improve graft retention as well as graft-specific immunoprotection during allograft transplantation.

A Collaborative Analysis of Individual Participant Data from 19 Prospective Studies Assesses Circulating Vitamin D and Prostate Cancer Risk.

Previous prospective studies assessing the relationship between circulating concentrations of vitamin D and prostate cancer risk have shown inconclusive results, particularly for risk of aggressive disease. In this study, we examine the association between prediagnostic concentrations of 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)2D] and the risk of prostate cancer overall and by tumor characteristics. Principal investigators of 19 prospective studies provided individual participant data on circulating 25(OH)D and 1,25(OH)2D for up to 13,462 men with incident prostate cancer and 20,261 control participants. ORs for prostate cancer by study-specific fifths of season-standardized vitamin D concentration were estimated using multivariable-adjusted conditional logistic regression. 25(OH)D concentration was positively associated with risk for total prostate cancer (multivariable-adjusted OR comparing highest vs. lowest study-specific fifth was 1.22; 95% confidence interval, 1.13-1.31; P trend < 0.001). However, this association varied by disease aggressiveness (P heterogeneity = 0.014); higher circulating 25(OH)D was associated with a higher risk of nonaggressive disease (OR per 80 percentile increase = 1.24, 1.13-1.36) but not with aggressive disease (defined as stage 4, metastases, or prostate cancer death, 0.95, 0.78-1.15). 1,25(OH)2D concentration was not associated with risk for prostate cancer overall or by tumor characteristics. The absence of an association of vitamin D with aggressive disease does not support the hypothesis that vitamin D deficiency increases prostate cancer risk. Rather, the association of high circulating 25(OH)D concentration with a higher risk of nonaggressive prostate cancer may be influenced by detection bias. SIGNIFICANCE: This international collaboration comprises the largest prospective study on blood vitamin D and prostate cancer risk and shows no association with aggressive disease but some evidence of a higher risk of nonaggressive disease.

Identification and characterization of a rich population of CD34+ mesenchymal stem/stromal cells in human parotid, sublingual and submandibular glands.

Mesenchymal stem/stromal cells (MSCs) play crucial roles in maintaining tissue homeostasis during physiological turnovers and injuries. Very little is known about the phenotype, distribution and molecular nature of MSCs in freshly isolated human salivary glands (SGs) as most reports have focused on the analysis of cultured MSCs. Our results demonstrate that the cell adhesion molecule CD34 was widely expressed by the MSCs of human major SGs, namely parotid (PAG), sublingual (SLG) and submandibular (SMG) glands. Further, gene expression analysis of CD34+ cells derived from fetal SMGs showed significant upregulation of genes involved in cellular adhesion, proliferation, branching, extracellular matrix remodeling and organ development. Moreover, CD34+ SMG cells exhibited elevated expression of genes encoding extracellular matrix, basement membrane proteins, and members of ERK, FGF and PDGF signaling pathways, which play key roles in glandular development, branching and homeostasis. In vitro CD34+ cell derived SG-MSCs revealed multilineage differentiation potential. Intraglandular transplantation of cultured MSCs in immunodeficient mice led to their engraftment in the injected and uninjected contralateral and ipsilateral glands. Engrafted cells could be localized to the stroma surrounding acini and ducts. In summary, our data show that CD34+ derived SG-MSCs could be a promising cell source for adoptive cell-based SG therapies, and bioengineering of artificial SGs.

Genomic analysis of penicillin-resistant Streptococcus pneumoniae in Southeastern Michigan.

OBJECTIVE: The emergence of multidrug resistance within Streptococcus pneumoniae population was analysed, correlating penicillin resistance Pen(R) with secondary antibiotic resistance, capsular serotype, and genetic diversity among isolates. METHODS: DNA fingerprinting, following macro-restriction enzyme digestion and pulse field gel electrophoresis (PFGE), and restriction fragment analysis of the PBP 2b gene, following PCR amplification, were performed on the Pen(R) S. pneumoniae, among 377 clinical isolates obtained from the clinical microbiology laboratory (University of Michigan Medical Center). RESULTS: Overall 35% of the isolates were Pen(R) of which 45% demonstrated high-level penicillin (Pen(R)-R, MIC>1). Respiratory isolates were more likely to be Pen(R) (p <0.001) than non-respiratory isolates and the rate of Pen(R)-R was significantly increased in children <10 years of age (59.6%, p <0.02). Secondary antibiotic resistance was more frequently associated with Pen(R)-R. Genomic DNA fingerprinting analysis and restriction fragment analysis of the PBP 2b gene demonstrated genomic divergence with discrete conserved pattern in the PBP 2b gene among the resistant isolates. CONCLUSION: The emergence of multidrug resistance in the S. pneumoniae population in SE Michigan is not due to expansion of a single or limited number of resistant clones, is occurring most frequently in the paediatric population and is associated with a decreased susceptibility to penicillin.