Infection-induced plasmablasts are a nutrient sink that impairs humoral immunity to malaria.

Plasmodium parasite-specific antibodies are critical for protection against malaria, yet the development of long-lived and effective humoral immunity against Plasmodium takes many years and multiple rounds of infection and cure. Here, we report that the rapid development of short-lived plasmablasts during experimental malaria unexpectedly hindered parasite control by impeding germinal center responses. Metabolic hyperactivity of plasmablasts resulted in nutrient deprivation of the germinal center reaction, limiting the generation of memory B cell and long-lived plasma cell responses. Therapeutic administration of a single amino acid to experimentally infected mice was sufficient to overcome the metabolic constraints imposed by plasmablasts and enhanced parasite clearance and the formation of protective humoral immune memory responses. Thus, our studies not only challenge the current model describing the role and function of blood-stage Plasmodium-induced plasmablasts but they also reveal new targets and strategies to improve anti-Plasmodium humoral immunity.

An orexigenic subnetwork within the human hippocampus.

Only recently have more specific circuit-probing techniques become available to inform previous reports implicating the rodent hippocampus in orexigenic appetitive processing1-4. This function has been reported to be mediated at least in part by lateral hypothalamic inputs, including those involving orexigenic lateral hypothalamic neuropeptides, such as melanin-concentrating hormone5,6. This circuit, however, remains elusive in humans. Here we combine tractography, intracranial electrophysiology, cortico-subcortical evoked potentials, and brain-clearing 3D histology to identify an orexigenic circuit involving the lateral hypothalamus and converging in a hippocampal subregion. We found that low-frequency power is modulated by sweet-fat food cues, and this modulation was specific to the dorsolateral hippocampus. Structural and functional analyses of this circuit in a human cohort exhibiting dysregulated eating behaviour revealed connectivity that was inversely related to body mass index. Collectively, this multimodal approach describes an orexigenic subnetwork within the human hippocampus implicated in obesity and related eating disorders.

Replication fork reversal in eukaryotes: from dead end to dynamic response.

The remodelling of replication forks into four-way junctions following replication perturbation, known as fork reversal, was hypothesized to promote DNA damage tolerance and repair during replication. Albeit conceptually attractive, for a long time fork reversal in vivo was found only in prokaryotes and specific yeast mutants, calling its evolutionary conservation and physiological relevance into question. Based on the recent visualization of replication forks in metazoans, fork reversal has emerged as a global, reversible and regulated process, with intriguing implications for replication completion, chromosome integrity and the DNA damage response. The study of the putative in vivo roles of recently identified eukaryotic factors in fork remodelling promises to shed new light on mechanisms of genome maintenance and to provide novel attractive targets for cancer therapy.

Tumoural activation of TLR3-SLIT2 axis in endothelium drives metastasis.

Blood vessels support tumours by providing nutrients and oxygen, while also acting as conduits for the dissemination of cancer1. Here we use mouse models of breast and lung cancer to investigate whether endothelial cells also have active 'instructive' roles in the dissemination of cancer. We purified genetically tagged endothelial ribosomes and their associated transcripts from highly and poorly metastatic tumours. Deep sequencing revealed that metastatic tumours induced expression of the axon-guidance gene Slit2 in endothelium, establishing differential expression between the endothelial (high Slit2 expression) and tumoural (low Slit2 expression) compartments. Endothelial-derived SLIT2 protein and its receptor ROBO1 promoted the migration of cancer cells towards endothelial cells and intravasation. Deleting endothelial Slit2 suppressed metastatic dissemination in mouse models of breast and lung cancer. Conversely, deletion of tumoural Slit2 enhanced metastatic progression. We identified double-stranded RNA derived from tumour cells as an upstream signal that induces expression of endothelial SLIT2 by acting on the RNA-sensing receptor TLR3. Accordingly, a set of endogenous retroviral element RNAs were upregulated in metastatic cells and detected extracellularly. Thus, cancer cells co-opt innate RNA sensing to induce a chemotactic signalling pathway in endothelium that drives intravasation and metastasis. These findings reveal that endothelial cells have a direct instructive role in driving metastatic dissemination, and demonstrate that a single gene (Slit2) can promote or suppress cancer progression depending on its cellular source.

Electrical Stimulation of Temporal and Limbic Circuitry Produces Distinct Responses in Human Ventral Temporal Cortex.

The human ventral temporal cortex (VTC) is highly connected to integrate visual perceptual inputs with feedback from cognitive and emotional networks. In this study, we used electrical brain stimulation to understand how different inputs from multiple brain regions drive unique electrophysiological responses in the VTC. We recorded intracranial EEG data in 5 patients (3 female) implanted with intracranial electrodes for epilepsy surgery evaluation. Pairs of electrodes were stimulated with single-pulse electrical stimulation, and corticocortical evoked potential responses were measured at electrodes in the collateral sulcus and lateral occipitotemporal sulcus of the VTC. Using a novel unsupervised machine learning method, we uncovered 2-4 distinct response shapes, termed basis profile curves (BPCs), at each measurement electrode in the 11-500 ms after stimulation interval. Corticocortical evoked potentials of unique shape and high amplitude were elicited following stimulation of several regions and classified into a set of four consensus BPCs across subjects. One of the consensus BPCs was primarily elicited by stimulation of the hippocampus; another by stimulation of the amygdala; a third by stimulation of lateral cortical sites, such as the middle temporal gyrus; and the final one by stimulation of multiple distributed sites. Stimulation also produced sustained high-frequency power decreases and low-frequency power increases that spanned multiple BPC categories. Characterizing distinct shapes in stimulation responses provides a novel description of connectivity to the VTC and reveals significant differences in input from cortical and limbic structures.SIGNIFICANCE STATEMENT Disentangling the numerous input influences on highly connected areas in the brain is a critical step toward understanding how brain networks work together to coordinate human behavior. Single-pulse electrical stimulation is an effective tool to accomplish this goal because the shapes and amplitudes of signals recorded from electrodes are informative of the synaptic physiology of the stimulation-driven inputs. We focused on targets in the ventral temporal cortex, an area strongly implicated in visual object perception. By using a data-driven clustering algorithm, we identified anatomic regions with distinct input connectivity profiles to the ventral temporal cortex. Examining high-frequency power changes revealed possible modulation of excitability at the recording site induced by electrical stimulation of connected regions.

Signatures of Electrical Stimulation Driven Network Interactions in the Human Limbic System.

Stimulation-evoked signals are starting to be used as biomarkers to indicate the state and health of brain networks. The human limbic network, often targeted for brain stimulation therapy, is involved in emotion and memory processing. Previous anatomic, neurophysiological, and functional studies suggest distinct subsystems within the limbic network (Rolls, 2015). Studies using intracranial electrical stimulation, however, have emphasized the similarities of the evoked waveforms across the limbic network. We test whether these subsystems have distinct stimulation-driven signatures. In eight patients (four male, four female) with drug-resistant epilepsy, we stimulated the limbic system with single-pulse electrical stimulation. Reliable corticocortical evoked potentials (CCEPs) were measured between hippocampus and the posterior cingulate cortex (PCC) and between the amygdala and the anterior cingulate cortex (ACC). However, the CCEP waveform in the PCC after hippocampal stimulation showed a unique and reliable morphology, which we term the "limbic Hippocampus-Anterior nucleus of the thalamus-Posterior cingulate, HAP-wave." This limbic HAP-wave was visually distinct and separately decoded from the CCEP waveform in ACC after amygdala stimulation. Diffusion MRI data show that the measured end points in the PCC overlap with the end points of the parolfactory cingulum bundle rather than the parahippocampal cingulum, suggesting that the limbic HAP-wave may travel through fornix, mammillary bodies, and the anterior nucleus of the thalamus (ANT). This was further confirmed by stimulating the ANT, which evoked the same limbic HAP-wave but with an earlier latency. Limbic subsystems have unique stimulation-evoked signatures that may be used in the future to help network pathology diagnosis.SIGNIFICANCE STATEMENT The limbic system is often compromised in diverse clinical conditions, such as epilepsy or Alzheimer's disease, and characterizing its typical circuit responses may provide diagnostic insight. Stimulation-evoked waveforms have been used in the motor system to diagnose circuit pathology. We translate this framework to limbic subsystems using human intracranial stereo EEG (sEEG) recordings that measure deeper brain areas. Our sEEG recordings describe a stimulation-evoked waveform characteristic to the memory and spatial subsystem of the limbic network that we term the "limbic HAP-wave." The limbic HAP-wave follows anatomic white matter pathways from hippocampus to thalamus to the posterior cingulum and shows promise as a distinct biomarker of signaling in the human brain memory and spatial limbic network.

Impedance Rhythms in Human Limbic System.

The impedance is a fundamental electrical property of brain tissue, playing a crucial role in shaping the characteristics of local field potentials, the extent of ephaptic coupling, and the volume of tissue activated by externally applied electrical brain stimulation. We tracked brain impedance, sleep-wake behavioral state, and epileptiform activity in five people with epilepsy living in their natural environment using an investigational device. The study identified impedance oscillations that span hours to weeks in the amygdala, hippocampus, and anterior nucleus thalamus. The impedance in these limbic brain regions exhibit multiscale cycles with ultradian (∼1.5-1.7 h), circadian (∼21.6-26.4 h), and infradian (∼20-33 d) periods. The ultradian and circadian period cycles are driven by sleep-wake state transitions between wakefulness, nonrapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep. Limbic brain tissue impedance reaches a minimum value in NREM sleep, intermediate values in REM sleep, and rises through the day during wakefulness, reaching a maximum in the early evening before sleep onset. Infradian (∼20-33 d) impedance cycles were not associated with a distinct behavioral correlate. Brain tissue impedance is known to strongly depend on the extracellular space (ECS) volume, and the findings reported here are consistent with sleep-wake-dependent ECS volume changes recently observed in the rodent cortex related to the brain glymphatic system. We hypothesize that human limbic brain ECS changes during sleep-wake state transitions underlie the observed multiscale impedance cycles. Impedance is a simple electrophysiological biomarker that could prove useful for tracking ECS dynamics in human health, disease, and therapy.SIGNIFICANCE STATEMENT The electrical impedance in limbic brain structures (amygdala, hippocampus, anterior nucleus thalamus) is shown to exhibit oscillations over multiple timescales. We observe that impedance oscillations with ultradian and circadian periodicities are associated with transitions between wakefulness, NREM, and REM sleep states. There are also impedance oscillations spanning multiple weeks that do not have a clear behavioral correlate and whose origin remains unclear. These multiscale impedance oscillations will have an impact on extracellular ionic currents that give rise to local field potentials, ephaptic coupling, and the tissue activated by electrical brain stimulation. The approach for measuring tissue impedance using perturbational electrical currents is an established engineering technique that may be useful for tracking ECS volume.

DEGRO guideline for personalized radiotherapy of brain metastases and leptomeningeal carcinomatosis in patients with breast cancer.

PURPOSE: The aim of this review was to evaluate the existing evidence for radiotherapy for brain metastases in breast cancer patients and provide recommendations for the use of radiotherapy for brain metastases and leptomeningeal carcinomatosis. MATERIALS AND METHODS: For the current review, a PubMed search was conducted including articles from 01/1985 to 05/2023. The search was performed using the following terms: (brain metastases OR leptomeningeal carcinomatosis) AND (breast cancer OR breast) AND (radiotherapy OR ablative radiotherapy OR radiosurgery OR stereotactic OR radiation). CONCLUSION AND RECOMMENDATIONS: Despite the fact that the biological subtype of breast cancer influences both the occurrence and relapse patterns of breast cancer brain metastases (BCBM), for most scenarios, no specific recommendations regarding radiotherapy can be made based on the existing evidence. For a limited number of BCBM (1-4), stereotactic radiosurgery (SRS) or fractionated stereotactic radiotherapy (SRT) is generally recommended irrespective of molecular subtype and concurrent/planned systemic therapy. In patients with 5-10 oligo-brain metastases, these techniques can also be conditionally recommended. For multiple, especially symptomatic BCBM, whole-brain radiotherapy (WBRT), if possible with hippocampal sparing, is recommended. In cases of multiple asymptomatic BCBM (≥ 5), if SRS/SRT is not feasible or in disseminated brain metastases (> 10), postponing WBRT with early reassessment and reevaluation of local treatment options (8-12 weeks) may be discussed if a HER2/Neu-targeting systemic therapy with significant response rates in the central nervous system (CNS) is being used. In symptomatic leptomeningeal carcinomatosis, local radiotherapy (WBRT or local spinal irradiation) should be performed in addition to systemic therapy. In patients with disseminated leptomeningeal carcinomatosis in good clinical condition and with only limited or stable extra-CNS disease, craniospinal irradiation (CSI) may be considered. Data regarding the toxicity of combining systemic therapies with cranial and spinal radiotherapy are sparse. Therefore, no clear recommendations can be given, and each case should be discussed individually in an interdisciplinary setting.

Centromedian thalamic deep brain stimulation for idiopathic generalized epilepsy: Connectivity and target optimization.

There are limited treatment options for individuals with drug-resistant idiopathic generalized epilepsy (IGE). Small, limited case series suggest that centromedian thalamus deep brain stimulation (CM-DBS) may be an effective treatment option. The optimal CM-DBS target for IGE is underexamined. Here, we present a retrospective analysis of CM-DBS targeting and efficacy for five patients with drug-resistant IGE. Volume of tissue activated (VTA) overlap with CM nucleus was performed using an open-source toolbox. Median follow-up time was 13 months. Median convulsive seizure frequency reduction was 66%. One patient had only absence seizures, with >99% reduction in absence seizure frequency. Four patients had electrode contacts positioned within the CM nucleus target, all of whom had >50% reduction in primary semiology seizure, with 85% median seizure reduction (p = .004, paired-sample t test). Volumetric "sweet-spot" mapping revealed that best outcomes were correlated with stimulation of the middle ventral CM nucleus. Connectivity strength between the sweet-spot region and central peri-Rolandic cortex was increased significantly relative to other cortical regions (p = 8.6 × 10-4, Mann-Whitney U test). Our findings indicate that CM-DBS can be an effective treatment for patients with IGE, highlight the importance of accurate targeting and targeting analysis, and within the context of prior work, suggest that ideal CM-DBS targets may be syndrome specific.

Canonical Response Parameterization: Quantifying the structure of responses to single-pulse intracranial electrical brain stimulation.

Single-pulse electrical stimulation in the nervous system, often called cortico-cortical evoked potential (CCEP) measurement, is an important technique to understand how brain regions interact with one another. Voltages are measured from implanted electrodes in one brain area while stimulating another with brief current impulses separated by several seconds. Historically, researchers have tried to understand the significance of evoked voltage polyphasic deflections by visual inspection, but no general-purpose tool has emerged to understand their shapes or describe them mathematically. We describe and illustrate a new technique to parameterize brain stimulation data, where voltage response traces are projected into one another using a semi-normalized dot product. The length of timepoints from stimulation included in the dot product is varied to obtain a temporal profile of structural significance, and the peak of the profile uniquely identifies the duration of the response. Using linear kernel PCA, a canonical response shape is obtained over this duration, and then single-trial traces are parameterized as a projection of this canonical shape with a residual term. Such parameterization allows for dissimilar trace shapes from different brain areas to be directly compared by quantifying cross-projection magnitudes, response duration, canonical shape projection amplitudes, signal-to-noise ratios, explained variance, and statistical significance. Artifactual trials are automatically identified by outliers in sub-distributions of cross-projection magnitude, and rejected. This technique, which we call "Canonical Response Parameterization" (CRP) dramatically simplifies the study of CCEP shapes, and may also be applied in a wide range of other settings involving event-triggered data.

Clinical pharmacology in adolescent transgender medicine.

Adolescent transgender medicine is a growing clinical field. Gender-affirming medications for transgender youth may include gonadotropin-releasing hormone (GnRH) agonists, gender-affirming hormones or both. To evaluate the potential effects of GnRH agonists (puberty suppression) on pharmacokinetic processes for transgender youth, we searched PubMed from inception to May 2024 for publications on the effects of GnRH agonists on drug absorption, distribution, metabolism or excretion for transgender adolescents or effects on hormones (including gonadotropins, adrenal androgens, sex steroids) that are associated with changes in drug metabolism during puberty in the general adolescent population. No publications discussed the effects of GnRH agonist treatment on pharmacokinetic processes for adolescent transgender people. Sixteen publications observed marked decreases in gonadotropins and sex steroids for both adolescent transgender men and adolescent transgender women and slight effects on adrenal androgens. During GnRH agonist treatment, changes in body composition and body shape were greater for adolescent transgender people than for cisgender adolescent people. Further research is needed to better understand the effects of GnRH agonists on drug metabolism and other pharmacokinetic processes for transgender adolescents receiving GnRH agonists and other gender-affirming medications.

Determinants of HIV Testing Among Migrant Men Who Have Sex With Men from Sub-Saharan Africa and Other Regions Residing in 10 European Countries.

Migrant men who have sex with men (mMSM) from sub-Saharan Africa (SSA) and other regions outside Europe are highly vulnerable to HIV. However, research on the determinants of HIV testing among mMSM from SSA, and how these differ across the categories of mMSM living in Europe, is limited. Using data from the European MSM Internet Survey (EMIS-2017), we assessed HIV testing prevalence and recency in mMSM from SSA and other mMSM residing in ten European countries, as well as the determinants of HIV testing across different mMSM categories with logistic regression analyses. Ever-testing for HIV was slightly higher in mMSM from SSA (83%) compared to other mMSM categories (75-80%), except for mMSM from Latin America and Caribbean region (84%). Overall, 20% of mMSM had never tested. In multivariable analysis, higher age (adjusted odds ratio [AOR] 1.05, 95% confidence interval [CI] 1.01-1.10), higher HIV knowledge (AOR 1.45, 95%-CI 1.11-1.90), and residence in smaller settlements (AOR 0.45, 95%-CI 0.21-0.96) were significantly associated with ever testing for HIV in mMSM from SSA. Comparing mMSM from SSA to mMSM from other regions, we found varying significant similarities (higher age, residence in smaller settlements and HIV knowledge) and differences (lower educational attainment, not identifying as gay, being a student, and limited disclosure of homosexual attraction) in the determinants of ever-testing for HIV. Community-specific interventions addressing identified sociodemographic and behavioral determinants to increase HIV testing uptake in the different mMSM categories and better data for further research are warranted.

Intention and preference to use long-acting injectable PrEP among MSM in the Netherlands: a diffusion of innovation approach.

Long-acting injectable pre-exposure prophylaxis (LAI-PrEP) is efficacious in preventing HIV among men-who-have-sex-with-men (MSM) and will be soon available in Europe. This study investigated the intention and preference to use LAI-PrEP among MSM in the Netherlands by employing a diffusion of innovation approach. This study had a cross-sectional design nested within a cohort study established in 2017 to understand oral PrEP use among MSM. 309 MSM completed the survey on their awareness, interest, intention, and preference for LAI-PrEP in June 2022. Among them, 83% showed high/very-high interest in, and 63% showed high/very-high intention to use LAI-PrEP. A repeated innovator effect from the early adopters to LAI-PrEP was not observed. Early adopters did not show increased intention to use LAI-PrEP compared to other MSM subgroups, but neither did PrEP-naïve nor PrEP-discontinued MSM. However, among the 218 current oral PrEP users, suboptimal adherence was associated with preference for LAI-PrEP but not with intention to use it. In conclusion, our findings indicated that an effective, available, and affordable LAI-PrEP would be welcomed in the Netherlands, but that its introduction may not significantly expand PrEP coverage. However, the introduction of LAI-PrEP in the Netherlands could prove beneficial to MSM with suboptimal adherence to oral PrEP.

Engagement of HIV-negative MSM and partners of people with HIV in HIV cure (research): exploring the influence of perceived severity, susceptibility, benefits, and concerns.

As the prospect of an HIV cure is gaining prominence, engaging key populations affected by an HIV cure becomes essential. This study examined the engagement of HIV-negative men who have sex with men (MSM) and/or partners of people with HIV (PHIV) in the Netherlands. Interviews were conducted with 19 MSM not in relationships with a partner with HIV and 16 partners of PHIV and were thematically analyzed. Perspectives on the importance of an HIV cure were shaped by the perceived severity of HIV and the level of susceptibility to the virus. Despite concerns about potential new HIV infections and treatment intensity, most participants believed that an HIV cure could reduce HIV burden. Both HIV eradication and HIV suppression were regarded as acceptable outcomes. Engagement was demonstrated through actions like accessing information, participating in research, and showing support for partners or community members involved in HIV cure research. In conclusion, we found that most participants were engaged due to their heightened perception of HIV's severity. However, this engagement tended to remain passive due to their perceived low susceptibility to HIV, resulting in a scenario where the perceived importance of an HIV cure is high, while personal relevance remains low.

Spatio-temporal distributions of COVID-19 vaccine doses uptake in the Netherlands: a Bayesian ecological modelling analysis.

In the transitioning era towards the COVID-19 endemic, there is still a sizable population that has never been vaccinated against COVID-19 in the Netherlands. This study employs Bayesian spatio-temporal modelling to assess the relative chances of COVID-19 vaccination uptake - first, second, and booster doses - both at the municipal and regional (public health services) levels. Incorporating ecological regression modelling to consider socio-demographic factors, our study unveils a diverse spatio-temporal distribution of vaccination uptake. Notably, the areas located in or around the Dutch main urban area (Randstad) and regions that are more religiously conservative exhibit a below-average likelihood of vaccination. Analysis at the municipal level within public health service regions indicates internal heterogeneity. Additionally, areas with a higher proportion of non-Western migrants consistently show lower chances of vaccination across vaccination dose scenarios. These findings highlight the need for tailored national and local vaccination strategies. Particularly, more regional efforts are essential to address vaccination disparities, especially in regions with elevated proportions of marginalized populations. This insight informs ongoing COVID-19 campaigns, emphasizing the importance of targeted interventions for optimizing health outcomes during the second booster phase, especially in regions with a relatively higher proportion of marginalized populations.

Patterns of Chemsex Substance Use and Its Association with HIV Transmission Risk Among Men Who Have Sex with Men in Thailand: A Latent Class Analysis.

Sexualized substance use or "chemsex" may contribute to the HIV epidemic among men who have sex with men (MSM) in Thailand. Specific patterns of chemsex use may be associated with different HIV/STI transmission risks. We examined typologies and correlates of sexualized substance use among a sample of high-risk MSM (n = 532) who had attended a private sex party or circuit party in the past three years using latent class analysis. Multinomial regression was used to adjust for variables associated with the 3-class latent class model. We identified a 3-class model as the best fitting model, which included: (1) "negligible sexualized substance users" (36.7%), who had never engaged in chemsex in the past six months; (2) "sexualized substance users" (13.9%), who had a high level of sexualized alcohol use and a wide range of other substances before or during sex in the past six months; and (3) "exclusive chemsex users" (49.4%), who predominantly used crystal methamphetamine, amyl nitrite, and erectile dysfunctional drugs before or during sex in the past six months. Compared to negligible sexualized substance users, exclusive chemsex users were more likely to be HIV-positive, more likely to have six or more sexual partners in the past six months, less likely to have condom use at last anal intercourse, and more likely to have provided sex work. Relative to negligible sexualized substance users, sexualized substance users reported more frequent online sex-seeking behaviors. These subgroups of Thai MSM have unique substance use patterns and HIV-related risk profiles, underscoring the importance of targeted HIV prevention strategies.

Time-efficient consultation hours in the department of gynecological endocrinology.

BACKGROUND: The aim was to conduct a benchmark pilot study to find the best practice for consultation hours in the field of gynecological endocrinology. Suitable benchmarking participants were found in China, Germany, Greece, and Switzerland. Specifically, the study aimed to find the most time-efficient and beneficial consultation type in gynecological endocrinology focused on menopause and whether a shorter face-to-face consultation correlates with lower patient satisfaction. METHODS: This was an observational study. To analyze the processes of all benchmarking participants three tools were used: a measurement of time needed for the different consultation types, a questionnaire for patients and one for physicians. The primary endpoint was the time measurement of first consultations. Secondary endpoints were the time measurements of follow-up consultations and phone consultations and patient satisfaction. RESULTS: The mean overall duration of a first consultation differed from 20.4 min to 39.7 min (p = 0.003), mainly based on differences of the mean time to acquire the patient history, 5.6 to 21.6 min (p < 0.001). The percentage of patients who felt they had enough time to discuss questions ranged from 70% to 100% (p < 0.001). The percentage of patients who felt fully understood by their physician ranged from 62.5% to 92% (p = 0.006). The duration of a first consultation did not correlate with patients feeling well consulted (r=-0.048, p = 0.557). CONCLUSIONS: A concise patient history that concentrates on the most relevant points can reduce the total consultation time. Reducing consultation time can be made without compromising how well patients feel consulted.

Socio-economic inequities in mental health problems and wellbeing among women working in the apparel and floriculture sectors: testing the mediating role of psychological capital, social support and tangible assets.

BACKGROUND: It is still unknown whether the mechanisms proposed by the Reserve Capacity Model (RCM) explaining socio-economic health and wellbeing inequities in high income countries can be applied to low-income countries. This study investigates whether different reserve capacities (intra-, inter-personal, and tangible) can explain the association between relative socio-economic position (SEP) and wellbeing outcome measures among Ethiopian women working in Foreign Direct Investment (FDI). METHOD: Using a cross-sectional design, we collected quantitative survey data among 2,515 women working in the apparel and floriculture sectors in Ethiopia, measuring GHQ-12 mental health problems, multi-dimensional wellbeing, relative SEP, psychological capital (PsyCap), social support (emotional and financial social support network), and tangible assets (e.g., owning mobile phone, having access to toilet facilities). We used cluster-adjusted structural equation modelling to test whether PsyCap, social support, and/or tangible assets mediate the association between relative SEP (IV) and GHQ-12 mental health problems and multi-dimensional wellbeing (DVs). RESULTS: PsyCap and the size of the financial support network significantly mediate the socio-economic gradient in both wellbeing outcomes. The size of the emotional social support network shows no association with multi-dimensional wellbeing and shows an unexpected negative association with GHQ-12 mental health problems scores, including a significant mediation effect. Tangible assets show no association with the wellbeing outcome measures and do not mediate socio-economic mental health problems and wellbeing inequities. CONCLUSIONS: The RCM can be applied in low-income countries, although in unexpected ways. Similar to findings from high-income countries, PsyCap and size of the financial social support network show significant mediation effects in explaining mental health problems and wellbeing inequities in Ethiopia. These reserves could therefore serve as a buffer for socio-economic inequities in mental health and wellbeing and can therefore assist in decreasing these inequities for women working in FDI sectors in Ethiopia.

Brief Report: Determinants of Potential Sexual Activity Reduction in the Face of the Mpox Epidemic.

BACKGROUND: The current mpox epidemic is most prevalent among men-who-have-sex-with-men (MSM). Vaccination programs are being rolled-out to curb the epidemic. Behavioural measures have been called for as well, for example, by the WHO and national public health authorities to reduce the number of sexual partners and sexual activity. We investigated intentions and determinants among Dutch MSM to follow such behavioural measures. METHODS: Early in July 2022, in the context of a dynamic ongoing epidemic, 394 MSM answered an online questionnaire investigating concepts such as perceived mpox risk, vaccination and behavioural change intentions and collecting socio-demographic and sexual behaviour information. RESULTS: The overall intentions to reduce number of partners and sexual activity were high, but only a minority had developed definite intentions. Determinant analysis revealed that dating/open relationship status was a positive predictor; vaccination intentions did not predict sexual behaviour change; those not on PrEP were more likely to change their sexual behaviour. Mpox infection concern was the main predictor for behaviour change intentions. CONCLUSIONS: Our results show that behavioural measures to avoid an mpox infection are present in majority of participants in our survey, but high intentions are held by a minority. Taking the historic complexity of behavioural change pleas among MSM into account sensitive, additional public health measures are necessary to reach and to inform MSM about potential benefits of sexual behaviour change.

Scenarios of future mpox outbreaks among men who have sex with men: a modelling study based on cross-sectional seroprevalence data from the Netherlands, 2022.

BackgroundFollowing the 2022-2023 mpox outbreak, crucial knowledge gaps exist regarding orthopoxvirus-specific immunity in risk groups and its impact on future outbreaks.AimWe combined cross-sectional seroprevalence studies in two cities in the Netherlands with mathematical modelling to evaluate scenarios of future mpox outbreaks among men who have sex with men (MSM).MethodsSerum samples were obtained from 1,065 MSM attending Centres for Sexual Health (CSH) in Rotterdam or Amsterdam following the peak of the Dutch mpox outbreak and the introduction of vaccination. For MSM visiting the Rotterdam CSH, sera were linked to epidemiological and vaccination data. An in-house developed ELISA was used to detect vaccinia virus (VACV)-specific IgG. These observations were combined with published data on serial interval and vaccine effectiveness to inform a stochastic transmission model that estimates the risk of future mpox outbreaks.ResultsThe seroprevalence of VACV-specific antibodies was 45.4% and 47.1% in Rotterdam and Amsterdam, respectively. Transmission modelling showed that the impact of risk group vaccination on the original outbreak was likely small. However, assuming different scenarios, the number of mpox cases in a future outbreak would be markedly reduced because of vaccination. Simultaneously, the current level of immunity alone may not prevent future outbreaks. Maintaining a short time-to-diagnosis is a key component of any strategy to prevent new outbreaks.ConclusionOur findings indicate a reduced likelihood of large future mpox outbreaks among MSM in the Netherlands under current conditions, but emphasise the importance of maintaining population immunity, diagnostic capacities and disease awareness.