Impact of race and ethnicity on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

Non-Hispanic Black patients are disproportionally affected by multiple myeloma (MM) and whether efficacy outcomes after autologous stem cell transplant (ASCT) differ by race and ethnicity remains an area of active investigation. This study included 449 patients enriched with a large proportion of non-Hispanic Black patients and sought to highlight the impact of race and ethnicity on outcomes after HDT-ASCT for patients with newly diagnosed MM. We found induction chemotherapy followed by high-dose therapy-ASCT and maintenance chemotherapy is associated with long-term PFS and OS, regardless of race or ethnicity.

Effectiveness of dance interventions for falls prevention in older adults: systematic review and meta-analysis.

INTRODUCTION: Fall prevention is a global health priority. Strength and balance exercise programmes are effective at reducing falls. Emerging literature suggests dance is an enjoyable and sociable form of exercise. However, there is little evidence that dance reduces fall incidence. METHODS: Systematic review and meta-analysis examining effectiveness and cost-effectiveness of dance for falls prevention in older adults. Five databases were searched with no restrictions on publication date or intervention settings. Risk of bias was assessed using variants of Cochrane Risk of bias tools, Mixed-Methods Appraisal and Drummond checklist as appropriate. Certainty of evidence was assessed using GRADE. RESULTS: Forty-one studies were included (19 RCTs, 13 quasi-experimental, two mixed-method, seven observational studies, 2,451 participants). Five types of dance interventions were identified: ballroom and Latin dance, dance exercise, cultural dance, dance therapy, and low-impact dance. Meta-analysis was only possible for functional outcome measures: Timed-Up-and-Go (dance versus usual care, mean difference (MD) = 1.36; 95% CI -3.57 to 0.85), Sit-to-Stand (dance versus exercise MD = -0.85; 95% CI -2.64 to 0.93: dance versus education MD = -1.64; 95% CI -4.12 to 0.85), Berg Balance Scale (dance versus usual care MD = 0.61; 95% CI -4.26 to 5.47). There was unexplained variance in effects and no significant differences between intervention and control groups. Overall, certainty of evidence was very low; we are uncertain about the effect of dance interventions in reducing falls. CONCLUSIONS: There is very low certainty evidence for dance as an alternative to strength and balance training if the aim is to prevent falls. No robust evidence on the cost-effectiveness of dance interventions for the prevention of falls was found. PROSPERO REGISTRATION: CRD42022382908.

Interventions for cold homes: a rapid review of the health impacts.

BACKGROUND: Cold homes are associated with an increased risk of adverse health outcomes for older people. To mitigate this risk, homes need to be heated to an appropriate temperature. This review aims to identify interventions designed to improve heating and temperatures within homes and summarize its impact on health, health service utilization and cost effectiveness. METHODS: A rapid review was conducted. Studies assessing the effects of structural, financial, or behavioural interventions designed to improve home temperatures of residents aged 18+ years were eligible. Searches were carried out in four databases. A search for grey literature, and backward and forward citation searching were performed. Data were summarized in a narrative synthesis and mapped using EPPI-Reviewer and EPPI-Mapper software. RESULTS: Eighteen studies reported across 19 publications were included. Structural interventions were associated with better mental health and quality of life, a reduction in health service utilization, and improvements in satisfaction with internal home temperature, social interactions and financial difficulties. The impact on physical health outcomes varied by age, gender and long-term conditions. Evidence about the impact of behavioural interventions was inconsistent. CONCLUSION: Structural improvements to increase home temperatures may offer the potential to improve some aspects of health. However, the impact on physical health, including which groups are most likely to benefit, is unclear. Key gaps include the lack of evidence about the impact of financial interventions, and the impact of all types of interventions, on quality of life, mortality and costs.

Impact of age, obesity, and renal impairment on outcomes after autologous stem cell transplantation for patients with newly diagnosed multiple myeloma.

INTRODUCTION: There remains a need to determine whether certain subgroups of newly diagnosed multiple myeloma (NDMM) derive the same benefit from high-dose chemotherapy-autologous stem cell transplant (HDT-ASCT). We describe our institutional experience highlighting the impact of age, obesity, and renal impairment on outcomes after HDT-ASCT for patients with NDMM in a real-world setting. METHODS: A total of 449 consecutive patients were included in this retrospective analysis. RESULTS: No difference in median progression free survival or overall survival was seen for patients with age > 65, body mass index (BMI) > 30 kg/m2, or estimated glomerular filtration rate < 60 mL/min/1.73 m2 when compared to those without these characteristics. From a safety standpoint, there were no differences in the incidence of transplant-related mortality or secondary malignancy among subgroups. CONCLUSION: For patients with NDMM undergoing HDT-ASCT, there is no difference in outcomes based on age, BMI, or renal function, and the presence of one or more of these factors should not preclude patients from HDT-ASCT.

Interventions Based on Behavior Change Techniques to Encourage Physical Activity or Decrease Sedentary Behavior in Community-Dwelling Adults Aged 50-70: Systematic Review With Intervention Component Analysis.

Increasing physical activity (PA) and/or decreasing sedentary behaviors is important in the delay and prevention of long-term conditions. PA can help maintain function and independence and decrease the need for hospitalization/institutionalization. Activity rates often decline in later life resulting in a need for interventions that encourage uptake and adherence through the use of Behavior Change Techniques (BCTs). We conducted a systematic review of the evidence for interventions that included BCTs in community-dwelling adults with a mean age of 50-70. The review followed PRISMA guidelines. The interventions were psychosocial, nonpharmacological, and noninvasive interventions utilizing components based on BCTs that evaluated change in PA and/or sedentary behavior. Intervention Component Analysis (ICA) was used to synthesize effectiveness of intervention components. Twelve randomized controlled trials were included in this review. The mean sample age was 50-64. Thirteen BCTs were used across all studies, and the most commonly used techniques were goals and planning, feedback and monitoring, and natural consequences. Seven intervention components linked with BCTs were found: personalized goal setting, tailored feedback from facilitators, on-site and postintervention support, education materials and resources, reinforcing change on behavior and attitudes, self-reported monitoring, and social connectedness. All components, except for social connectedness, were associated with improved health behavior and PA levels. The interventions that use BCTs have incorporated strategies that reinforce change in behavior and attitudes toward PA.

Phosphatidic acid produced by phospholipase D is required for hyphal cell-cell fusion and fungal-plant symbiosis.

Although lipid signaling has been shown to serve crucial roles in mammals and plants, little is known about this process in filamentous fungi. Here we analyze the contribution of phospholipase D (PLD) and its product phosphatidic acid (PA) in hyphal morphogenesis and growth of Epichloë festucae and Neurospora crassa, and in the establishment of a symbiotic interaction between E. festucae and Lolium perenne. Growth of E. festucae and N. crassa PLD deletion strains in axenic culture, and for E. festucae in association with L. perenne, were analyzed by light-, confocal- and electron microscopy. Changes in PA distribution were analyzed in E. festucae using a PA biosensor and the impact of these changes on the endocytic recycling and superoxide production investigated. We found that E. festucae PldB, and the N. crassa ortholog, PLA-7, are required for polarized growth and cell fusion and contribute to ascospore development, whereas PldA/PLA-8 are dispensable for these functions. Exogenous addition of PA rescues the cell-fusion phenotype in E. festucae. PldB is also crucial for E. festucae to establish a symbiotic association with L. perenne. This study identifies a new component of the cell-cell communication and cell fusion signaling network for hyphal morphogenesis and growth of filamentous fungi.

Regulation of host-infection ability in the grass-symbiotic fungus Epichloë festucae by histone H3K9 and H3K36 methyltransferases.

Recent studies have identified key genes that control the symbiotic interaction between Epichloë festucae and Lolium perenne. Here we report on the identification of specific E. festucae genes that control host infection. Deletion of setB, which encodes a homologue of the H3K36 histone methyltransferase Set2/KMT3, reduced histone H3K36 trimethylation and led to severe defects in colony growth and hyphal development. The E. festucae ΔclrD mutant, which lacks the gene encoding the homologue of the H3K9 methyltransferase KMT1, displays similar developmental defects. Both mutants are completely defective in their ability to infect L. perenne. Alleles that complement the culture and plant phenotypes of both mutants also complement the histone methylation defects. Co-inoculation of either ΔsetB or ΔclrD with the wild-type strain enables these mutants to colonize the host. However, successful colonization by the mutants resulted in death or stunting of the host plant. Transcriptome analysis at the early infection stage identified four fungal candidate genes, three of which encode small-secreted proteins, that are differentially regulated in these mutants compared to wild type. Deletion of crbA, which encodes a putative carbohydrate binding protein, resulted in significantly reduced host infection rates by E. festucae.

Host apoplastic cysteine protease activity is suppressed during the mutualistic association of Lolium perenne and Epichloë festucae.

Plants secrete various defence-related proteins into the apoplast, including proteases. Papain-like cysteine proteases (PLCPs) are central components of the plant immune system. To overcome plant immunity and successfully colonize their hosts, several plant pathogens secrete effector proteins inhibiting plant PLCPs. We hypothesized that not only pathogens, but also mutualistic microorganisms interfere with PLCP-meditated plant defences to maintain endophytic colonization with their hosts. Epichloë festucae forms mutualistic associations with cool season grasses and produces a range of secondary metabolites that protect the host against herbivores. In this study, we performed a genome-wide identification of Lolium perenne PLCPs, analysed their evolutionary relationship, and classified them into nine PLCP subfamilies. Using activity-based protein profiling, we identified four active PLCPs in the apoplast of L. perenne leaves that are inhibited during endophyte interactions. We characterized the L. perenne cystatin LpCys1 for its inhibitory capacity against ryegrass PLCPs. LpCys1 abundance is not altered during the mutualistic interaction and it mainly inhibits LpCP2. However, since the activity of other L. perenne PLCPs is not sensitive to LpCys1, we propose that additional inhibitors, likely of fungal origin, are involved in the suppression of apoplastic PLCPs during E. festucae infection.

Ending AIDS in the Asia-Pacific region by 2030: are we on track? Policy, epidemiological and intervention insights.

The Asia-Pacific region is home to nearly 6 million people living with HIV. Across the region, key populations - men who have sex with men, transgender women, people who inject drugs, sex workers, prisoners - and their sexual partners make up the majority of those living with HIV. While significant progress has been made in the past 5 years towards UNAIDS's 90-90-90 goals (90% of people with HIV diagnosed, 90% on antiretroviral therapy, 90% virologically suppressed), significant gaps remain. The papers in this Special Issue address important questions: are we on track to end the AIDS epidemic in the Asia-Pacific region? And can countries in this region reach the new UNAIDS targets for 2030?

Demedicalisation of HIV interventions to end HIV in the Asia-Pacific.

Despite the challenges to the HIV response in the Asia-Pacific, a demedicalisation of HIV intervention has been demonstrated to be an important strategy to maximise the uptake of HIV prevention tools among key populations in this region. Demedicalisation of HIV interventions translates medical discourse and shifts the paradigm from a disease-focused to a people-centred approach. It also recognises real-life experiences of key populations in the HIV response by empowering them to voice their needs and be at the forefront of the epidemic control. We further categorise a demedicalisation approach into three frameworks: (1) the demystification of clinical or medical concerns; (2) the destigmatisation of people living with HIV; and (3) the decentralisation of healthcare services. This article reviewed the demedicalisation framework by looking at the HIV intervention examples from countries in the Asia-Pacific, which included: (1) a study on drug-drug interaction between pre-exposure prophylaxis and feminising hormone treatment for transgender women; (2) the roles of key population-led health services; and (3) certification of key population lay providers.

Prepped for PrEP? Acceptability, continuation and adherence among men who have sex with men and transgender women enrolled as part of Vietnam's first pre-exposure prophylaxis program.

Background HIV prevalence among men who have sex with men (MSM) and transgender women (TGW) in Vietnam is high, whereas coverage of effective HIV prevention services has been inadequate. Studies have measured MSM and TGW demand for pre-exposure prophylaxis (PrEP) services, which led to the design of the first ever PrEP program in Vietnam, Prepped for PrEP (P4P). METHODS: In March 2017, PrEP services were offered in Ho Chi Minh City as part of the P4P demonstration project, enabling same-day enrolment in three key population (KP)-led clinics and four public clinics. P4P aimed to assess acceptability and feasibility of PrEP services through calculating the rate of PrEP enrolment over time, and quarterly measures of continuation and adherence over an 18-month period. RESULTS: A total of 1069 MSM and 62 TGW were enrolled in P4P. Average monthly PrEP enrolment among MSM increased five-fold from the first 3 months (March-June 2017) to the last 3 months of active enrolment (March-June 2018), whereas for TGW, no increased trend in PrEP enrolment per quarter was seen. Self-reported PrEP adherence was >90% at all time points among MSM, but varied from 11.1% to 88.9% among TGW. PrEP continuation was calculated at months 3, 6, 9, 12, 15 and 18. For MSM, it was 88.7% at month 3, 68.8% at month 12 and 46.6% at month 18, whereas for TGW, it was 87.1%, 54.8% and 52.8%, respectively. Multivariable regression identified that MSM with lower-than-average income (adjusted odds ratio (aOR) 2.38 (95% confidence interval (CI): 1.59-3.54), P = 0.000), aged >30 years (aOR 2.03 (95% CI: 1.30-3.40), P = 0.007) and with an increasing number of sex partners (aOR: 1.06 (1.01-1.11), P = 0.011) had greater odds of remaining on PrEP. For TGW, being aged >30 years was associated with continuing on PrEP (aOR 5.62 (95% CI: 1.05-29.9), P = 0.043). CONCLUSIONS: We found PrEP to be highly acceptable among MSM and moderately acceptable among TGW. Continuation rates were relatively high for the first roll-out of PrEP; however, those aged ≤30 years were much more likely to discontinue services. Scaling-up PrEP through differentiated and community-led and engaged PrEP service delivery will be key to effectively increase access and uptake over the next 5 years.

Lolium perenne apoplast metabolomics for identification of novel metabolites produced by the symbiotic fungus Epichloë festucae.

Epichloë festucae is an endophytic fungus that forms a symbiotic association with Lolium perenne. Here we analysed how the metabolome of the ryegrass apoplast changed upon infection of this host with sexual and asexual isolates of E. festucae. A metabolite fingerprinting approach was used to analyse the metabolite composition of apoplastic wash fluid from uninfected and infected L. perenne. Metabolites enriched or depleted in one or both of these treatments were identified using a set of interactive tools. A genetic approach in combination with tandem MS was used to identify a novel product of a secondary metabolite gene cluster. Metabolites likely to be present in the apoplast were identified using MarVis in combination with the BioCyc and KEGG databases, and an in-house Epichloë metabolite database. We were able to identify the known endophyte-specific metabolites, peramine and epichloëcyclins, as well as a large number of unknown markers. To determine whether these methods can be applied to the identification of novel Epichloë-derived metabolites, we deleted a gene encoding a NRPS (lgsA) that is highly expressed in planta. Comparative MS analysis of apoplastic wash fluid from wild-type- vs mutant-infected plants identified a novel Leu/Ile glycoside metabolite present in the former.

Love, power, resilience and vulnerability: relationship dynamics between female sex workers in Ghana and their intimate partners.

Little is known about female sex workers' daily lives or emotional relationships. Using relational-cultural theory, this study explored the relationship dynamics between sex workers and their intimate partners in Kumasi, Ghana. We collected qualitative data from 37 male intimate partners through 24 in-depth interviews and two focus group discussions (FGDs) with 13 male partners. We also conducted three FGDs with 20 women involved in sex work. Relationships between sex workers and their intimate partners were mutual, reciprocal and transactional. Male partners provided protection for financial support, a place to sleep and intimacy. Both men and women described their relationships in terms of friendship, love and a hopeful future. Women were reluctant to quit sex work because they depended on it for income. Most respondents did not use condoms in these romantic relationships, citing trust, love, faithfulness and commitment. Both men and women described high levels of violence in their relationships. The context of sex work heightens vulnerability but also appears to facilitate resilience and creative coping strategies. The relational dynamics between sex workers and their intimate partners in Ghana merit further exploration to examine the extent to which women involved in sex work hold and exert power within these relationships.

IDC2 and IDC3, two genes involved in cell non-autonomous signaling of fruiting body development in the model fungus Podospora anserina.

Filamentous ascomycetes produce complex multicellular structures during sexual reproduction. Little is known about the genetic pathways enabling the construction of such structures. Here, with a combination of classical and reverse genetic methods, as well as genetic mosaic and graft analyses, we identify and provide evidence for key roles for two genes during the formation of perithecia, the sexual fruiting bodies, of the filamentous fungus Podospora anserina. Data indicate that the proteins coded by these two genes function cell-non-autonomously and that their activity depends upon conserved cysteines, making them good candidate for being involved in the transmission of a reactive oxygen species (ROS) signal generated by the PaNox1 NADPH oxidase inside the maturing fruiting body towards the PaMpk1 MAP kinase, which is located inside the underlying mycelium, in which nutrients are stored. These data provide important new insights to our understanding of how fungi build multicellular structures.

SymB and SymC, two membrane associated proteins, are required for Epichloë festucae hyphal cell-cell fusion and maintenance of a mutualistic interaction with Lolium perenne.

Cell-cell fusion in fungi is required for colony formation, nutrient transfer and signal transduction. Disruption of genes required for hyphal fusion in Epichloë festucae, a mutualistic symbiont of Lolium grasses, severely disrupts the host interaction phenotype. They examined whether symB and symC, the E. festucae homologs of Podospora anserina self-signaling genes IDC2 and IDC3, are required for E. festucae hyphal fusion and host symbiosis. Deletion mutants of these genes were defective in hyphal cell fusion, formed intra-hyphal hyphae, and had enhanced conidiation. SymB-GFP and SymC-mRFP1 localize to plasma membrane, septa and points of hyphal cell fusion. Plants infected with ΔsymB and ΔsymC strains were severely stunted. Hyphae of the mutants colonized vascular bundles, were more abundant than wild type in the intercellular spaces and formed intra-hyphal hyphae. Although these phenotypes are identical to those previously observed for cell wall integrity MAP kinase mutants no difference was observed in the basal level of MpkA phosphorylation or its cellular localization in the mutant backgrounds. Both genes contain binding sites for the transcription factor ProA. Collectively these results show that SymB and SymC are key components of a conserved signaling network for E. festucae to maintain a mutualistic symbiotic interaction within L. perenne.

Cigarette Smoking and Musculoskeletal Pain Severity Among Male and Female Afghanistan/Iraq Era Veterans.

OBJECTIVE: Cigarette smoking and musculoskeletal pain are prevalent among Department of Veterans Affairs (VA) health care system users. These conditions frequently co-occur; however, there is limited empirical information specific to Afghanistan/Iraq era veterans. The present study sought to examine gender differences in the association between cigarette smoking and moderate to severe musculoskeletal pain in US veterans with Afghanistan/Iraq era service. METHODS: A random sample of 5,000 veterans with service after November 11, 2001, participated in a survey assessing health care needs and barriers to care. One thousand ninety veterans completed the survey assessing post-traumatic stress disorder (PTSD) symptoms, depressive symptoms, and current pain severity. Multivariate logistic regression was used to examine the association between gender, cigarette smoking status, and current moderate to severe musculoskeletal pain. RESULTS: Findings indicated a significant gender by smoking interaction on moderate/severe musculoskeletal pain, adjusting for age, self-reported race/ethnicity and weight status, combat exposure, probable PTSD, depressive symptoms, service-connected injury during deployment, and VA health care service utilization. Deconstruction of the interaction indicated that female veteran smokers, relative to female nonsmokers, had increased odds of endorsing moderate to severe musculoskeletal pain (odds ratio [OR] = 2.73, 95% confidence interval [CI] = 1.16-6.41), whereas this difference was nonsignificant for male veterans (OR = 1.03, 95% CI = 0.69-1.56). CONCLUSIONS: Survey data from Operation Enduring Freedom/Operation Iraqi Freedom veterans suggest an association between current smoking, gender, and moderate to severe musculoskeletal pain. The stronger relationship between smoking and pain in women supports the need for interventional and longitudinal research that can inform gender-based risk factors for pain in veteran cigarette smokers.

The Relation of Light-to-Moderate Alcohol Consumption to Glucose Metabolism and Insulin Resistance in Nondiabetic Adults: the Moderating Effects of Depressive Symptom Severity, Adiposity, and Sex.

PURPOSE: We examined the relation of alcohol consumption to glucose metabolism and insulin resistance (IR) as a function of depressive symptoms, adiposity, and sex. METHOD: Healthy adults (aged 18-65 years) provided fasting blood samples and information on lifestyle factors. Alcohol intake was categorized as never, infrequent (1-3 drinks/month), occasional (1-7 drinks/week), and regular (≥2 drinks/day) drinkers. The Beck Depression Inventory (BDI) was used to assess symptom severity. Primary outcomes were fasting insulin, glucose, and IR assessed by the homeostasis model assessment (HOMA). RESULTS: In univariate analysis, alcohol consumption was negatively associated with HOMA-IR (p = 0.03), insulin (p = 0.007), and body mass index (BMI) (p = 0.04), but not with glucose or BDI. Adjusting for potential confounders including BMI, alcohol consumption was associated with HOMA-IR (p = 0.01) and insulin (p = 0.009) as a function of BDI and sex. For women with minimal depressive symptoms, light-to-moderate alcohol consumption was associated with lower HOMA-IR and insulin. Alcohol consumption was not associated with metabolic markers in women with higher depressive symptoms and in men. In analysis using BMI as a continuous moderator, alcohol consumption was only associated with insulin (p = 0.004). Post-hoc comparisons between BMI groups (<25 vs ≥25 kg/m2) revealed that light-to-moderate alcohol consumption was associated with lower insulin but only in subjects with BMI ≥ 25 kg/m2. CONCLUSIONS: The benefits of light-to-moderate alcohol consumption on fasting insulin and IR are sex dimorphic and appear to be independently moderated by adiposity and depressive symptom severity.

The endophytic symbiont Epichloë festucae establishes an epiphyllous net on the surface of Lolium perenne leaves by development of an expressorium, an appressorium-like leaf exit structure.

Epichloë festucae forms a mutualistic symbiotic association with Lolium perenne. This biotrophic fungus systemically colonizes the intercellular spaces of aerial tissues to form an endophytic hyphal network. E. festucae also grows as an epiphyte, but the mechanism for leaf surface colonization is not known. Here we identify an appressorium-like structure, which we call an expressorium that allows endophytic hyphae to penetrate the cuticle from the inside of the leaf to establish an epiphytic hyphal net on the surface of the leaf. We used a combination of scanning electron, transmission electron and confocal laser scanning microscopy to characterize this novel fungal structure and determine the composition of the hyphal cell wall using aniline blue and wheat germ agglutinin labelled with Alexafluor-488. Expressoria differentiate immediately below the cuticle in the leaf blade and leaf sheath intercalary cell division zones where the hyphae grow by tip growth. Differentiation of this structure requires components of both the NoxA and NoxB NADPH oxidase complexes. Major remodelling of the hyphal cell wall occurs following exit from the leaf. These results establish that the symbiotic association of E. festucae with L. perenne involves an interconnected hyphal network of both endophytic and epiphytic hyphae.

End Users' Views and Preferences on Prescribing and Taking Postexposure Prophylaxis for Prevention of HIV: Methods to Support World Health Organization Guideline Development.

The 2014 World Health Organization guidelines for human immunodeficiency virus postexposure prophylaxis (PEP) are the first to combine recommendations for all populations and exposures. To inform the development of these guidelines, we gathered views of end users on key aspects of PEP provision. A mixed-methods approach was used to gather views from the populations for whom the guideline will be of relevance. Data gathered from an online survey, focus group discussions, and previously collected data from in-depth interviews with key populations were used to inform the development of recommendations, in particular where there is a paucity of evidence to assess the benefits and harms of an intervention. This was a successful method to gather end users' views and preferences; however, limitations exist in the generalizability and reliability of the evidence. Future guideline development processes should consider methods to include the views of end users to guide the decision-making process.