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Cardiovascular disease (CVD) clinicians who care for seriously ill patients frequently report that they do not feel confident nor adequately prepared to manage patients' palliative care (PC) needs. With the goal, therefore, of increasing PC knowledge and skills amongst interprofessional clinicians providing CVD care, the ACC's PC Workgroup designed, developed, and implemented a comprehensive PC online educational activity. This paper describes the process and 13-month performance of this free, online activity for clinicians across disciplines and levels of training, "Palliative Care for the Cardiovascular Clinician" (PCCVC). A key component of PCCVC is that it is tailored to the lifelong learner; users can choose and receive credit for the activities that meet their individual learning needs. This webinar series was well-subscribed, and upon completion of the modules, learners reported better self-perceived abilities related to palliative care competencies. We propose PCCVC as a model for primary PC education for clinicians caring for individuals with other serious or life-shortening illnesses., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Markers of social health, including kinlessness, social isolation and loneliness, have important implications for quality of life and health for older adults. As the population ages, there is a growing cohort of kinless older adults without living partners or children, particularly among disadvantaged groups. Kinlessness has been associated with worse mental and physical health, significant unmet care needs, increased risk of dementia, higher rates of long-term placement, and higher mortality rates than those for patients with kin. Although other markers of social health have been studied in patients with heart failure, little is known about kinlessness in this population of patients. This review outlines the data on kinlessness and its impact on patients' outcomes, and it proposes novel interventions to mitigate its effects., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Competing Interests: Disclosures None.

Atherosclerosis is an inflammatory reaction that develops at specific regions within the artery wall and at specific sites of the arterial tree over a varying time frame in response to a variety of risk factors. The mechanisms that account for the interaction of systemic factors and atherosclerosis-susceptible regions of the arterial tree to mediate this site-specific development of atherosclerosis are not clear. The dynamics of blood flow has a major influence on where in the arterial tree atherosclerosis develops, priming the site for interactions with atherosclerotic risk factors and inducing cellular and molecular participants in atherogenesis. But how this accounts for lesion development at various locations along the vascular tree across differing time frames still requires additional study. Currently, murine models are favored for the experimental study of atherogenesis and provide the most insight into the mechanisms that may contribute to the development of atherosclerosis. Based largely on these studies, in this review, we discuss the role of hemodynamic shear stress, SR-B1, and other factors that may contribute to the site-specific development of atherosclerosis.

Background: Implantable cardioverter defibrillators (ICDs) decrease mortality in high-risk patients but can also cause distressing shocks near death. Patients who lack knowledge about their ICDs are more likely to have an active device at the end of life. Many hospice workers lack sufficient knowledge to educate patients about ICDs., Measures: An ICD educational video created for use in a diverse, underserved patient population was shown to hospice workers from two large community hospices and attendees of a regional conference. A validated 10 question survey was given to participants before and after the video., Outcomes: Significant improvement in ICD knowledge scores was seen in all participants (W = 3119.5, P < 0.0001). While doctors and nurses showed higher pretest knowledge, post-test knowledge scores equalized across all participants., Conclusions/lessons Learned: An ICD patient educational video designed for a diverse, underserved patient population effectively improved ICD knowledge to a uniform excellent level for a broad range of hospice workers., (Copyright © 2024 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: Palliative care (PC) is an essential component of high-quality care for people with cardiovascular disease (CVD). However, little is known about the current state of PC education in CVD training, including attitudes toward integration of PC into training and implementation of PC by the program's leadership., Methods: We developed a nationwide, cross-sectional survey that queried education approaches, perspectives and barriers to PC education in general CVD fellowship training. The survey was distributed to 392 members of the American College of Cardiology Program Director (PD) listserv, representing 290 general CVD fellowships between 1/2023 and 4/2023. We performed descriptive and ꭕ 2 analyses of survey data., Results: Of the program's representatives, 56 completed the survey (response rate = 19.3%). Respondents identified themselves as current PDs (89%), associate PDs (8.9%) or former PDs (1.8%), representing a diverse range of program sizes and types and regions of the country. Respondents reported the use of informal bedside teaching (88%), formal didactics (59%), online or self-paced modules (13%), in-person simulation (11%), and clinical rotations (16%) to teach PC content. Most programs covered PC topics at least annually, although there was variability by topic. We found no associations between program demographics and type or frequency of PC education. Most respondents reported dissatisfaction with the quantity (62%) or quality (59%) of the PC education provided. Barriers to PC education included an overabundance of other content to cover (36%) and perceived lack of fellow (20%) or faculty (18%) interest. Comments demonstrated the importance of PC education in fellowship, the lack of a requirement to provide PC education, difficulty in covering all topics, and suggestions of how PC skills should be taught., Conclusions: In a national survey of CVD educational leadership concerning approaches to PC education in CVD training, respondents highlighted both challenges to implementation of formal PC curricula in cardiology training and opportunities for comprehensive PC education., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Human gamma-D crystallin (HGD) is a major constituent of the eye lens. Aggregation of HGD contributes to cataract formation, the leading cause of blindness worldwide. It is unique in its longevity, maintaining its folded and soluble state for 50-60 years. One outstanding question is the structural basis of this longevity despite oxidative aging and environmental stressors including ultraviolet radiation (UV). Here we present crystallographic structures evidencing a UV-induced crystallin redox switch mechanism. The room-temperature serial synchrotron crystallographic (SSX) structure of freshly prepared crystallin mutant (R36S) shows no post-translational modifications. After aging for nine months in the absence of light, a thiol-adduct (dithiothreitol) modifying surface cysteines is observed by low-dose SSX. This is shown to be UV-labile in an acutely light-exposed structure. This suggests a mechanism by which a major source of crystallin damage, UV, may also act as a rescuing factor in a finely balanced redox system., (© 2024. The Author(s).)

In old age, impaired immunity causes high susceptibility to infections and cancer, higher morbidity and mortality, and poorer vaccination efficiency. Many factors, such as genetics, diet, and lifestyle, impact aging. This study aimed to investigate how immune responses change with age in healthy Dutch and Tanzanian individuals and identify common metabolites associated with an aged immune profile. We performed untargeted metabolomics from plasma to identify age-associated metabolites, and we correlated their concentrations with ex-vivo cytokine production by immune cells, DNA methylation-based epigenetic aging, and telomere length. Innate immune responses were impacted differently by age in Dutch and Tanzanian cohorts. Age-related decline in steroid hormone precursors common in both populations was associated with higher systemic inflammation and lower cytokine responses. Hippurate and 2-phenylacetamide, commonly more abundant in older individuals, were negatively correlated with cytokine responses and telomere length and positively correlated with epigenetic aging. Lastly, we identified several metabolites that might contribute to the stronger decline in innate immunity with age in Tanzanians. The shared metabolomic signatures of the two cohorts suggest common mechanisms of immune aging, revealing metabolites with potential contributions. These findings also reflect genetic or environmental effects on circulating metabolites that modulate immune responses., Competing Interests: Declaration of interests M.G.N. is a scientific founder and scientific advisory board member of Trained Therapeutix Discovery (TTxD), and is a scientific founder of Lemba and Biotrip. The other authors declare that they have no conflicts of interest., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Introduction: Brain abscesses are rare but potentially fatal condition and can be associated with cyanotic congenital heart disease of which 5-18.7% of these patients that develop cerebral abscess commonly have tetralogy of Fallot (TOF)., Case Presentation: We report a case of 3-year-old Muganda male that presented with convulsions, cyanosis and difficulty in breathing. The patient had a combination intervention of medical treatment and surgical drainage of the abscess. Post-operative Computerized tomography scan images and pre-operative brain Computerized tomography scans were compared. The multiple rings enhancing lesions were reduced in number and sizes. The largest measured ring was 44 × 22.5×16mm compared to the previous; 42 × 41×36mm. The mass effect had reduced from 16 mm to 7.5 mm. The periventricular hypodensities persisted. Findings showed radiological improvement with residual abscesses, subacute subdural hematoma and pneumocranium. The patient was treated with intravenous ceftriaxone 1 g OD for six weeks and he showed marked improvement and was discharged home after 3 months., Conclusion: A comprehensive strategy involving medications, surgical drainage, and early neurosurgical consultation is vital in treating brain abscesses in uncorrected TOF. Early identification of the pathogen, appropriate antibiotic therapy, and vigilant follow-up through clinical assessments and imaging are crucial, potentially spanning a 4-8-week treatment., (© 2024. The Author(s).)

Background: Platelets play a key role in hemostasis, inflammation, and cardiovascular diseases. Platelet reactivity is highly variable between individuals. The drivers of this variability in populations from Sub-Saharan Africa remain largely unknown., Objectives: We aimed to investigate the nongenetic and genetic determinants of platelet reactivity in healthy adults living in a rapidly urbanizing area in Northern Tanzania., Methods: Platelet activation and reactivity were measured by platelet P-selectin expression and the binding of fibrinogen in unstimulated blood and after ex vivo stimulation with adenosine diphosphate and PAR-1 and PAR-4 ligands. We then analyzed the associations of platelet parameters with host genetic and nongenetic factors, environmental factors, plasma inflammatory markers, and plasma metabolites., Results: Only a few associations were found between platelet reactivity parameters and plasma inflammatory markers and nongenetic host and environmental factors. In contrast, untargeted plasma metabolomics revealed a large number of associations with food-derived metabolites, including phytochemicals that were previously reported to inhibit platelet reactivity. Genome-wide single-nucleotide polymorphism genotyping identified 2 novel single-nucleotide polymorphisms (rs903650 and rs4789332) that were associated with platelet reactivity at the genome-wide level (P < 5 × 10 -8 ) as well as a number of variants in the PAR4 gene (F2RL3) that were associated with PAR4-induced reactivity., Conclusion: Our study uncovered factors that determine variation in platelet reactivity in a population in East Africa that is rapidly transitioning to an urban lifestyle, including the importance of genetic ancestry and the gradual abandoning of the traditional East African diet., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Post-traumatic seizures (PTS) are common among patients with depressed skull fractures (DSF). Understanding the burden of post traumatic seizures and the factors associated among adult patients with DSF is important to improve clinical care., Objective: To determine the prevalence and factors associated with post-traumatic seizures among adult patients with DSF at Mulago National Referral hospital (MNRH)., Methods: A cross-sectional study was conducted among 333 study participants between March 2021 and February 2022. Socio-demographic, clinical laboratory factors and anti-seizure medications were collected using a study questionnaire. Data was analysed to determine the prevalence of PTS and factors associated with occurrence of PTS among patients with DSF., Results: The mean age (±SD) of study participants was 31.2, (±10.5) years, with a male to female ratio of 10.4:1. Nearly half of the study participants had attained secondary level of education, while 31.6 % (105) were peasants (subsistence farmers). The overall prevalence of PTS among DSF study participants was 16.2 % (54participants). Late presentation of PTS was the highest at 9.0 % (30) followed by early PTS at 3.9 % [13] and immediate PTS at 3.3 % [11]. Moderate Glasgow coma score (GCS: 9-13), p < 0.015, severe traumatic brain injury (GCS: 3-8), p < 0.026 at the time of admission and midline brain shift (≥5mm), p < 0.009 were associated with PTS. Phenytoin (94.3 %) was the most commonly used ASM followed by phenobarbitone (1.4 %) and Valproate (1.1 %) among study participants., Conclusion: Patients with moderate and severe traumatic brain injury and midline brain shift were associated with post traumatic seizures. Early identification and intervention may reduce the burden of posttraumatic seizures in this category of patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Background: In the East African region, herbal plants are essential in the treatment and control of cancer. Given the diverse ecological and cultural makeup of the regional states, it is likely that different ethnic groups will use the same or different plants for the same or different diseases. However, since 2019, this has not been compiled into a single study., Purpose: The study aimed to compile and record the medicinal plants utilized in East Africa from April 2019 to June 2023 to treat various cancer types., Materials and Methods: The study examined 13 original studies that included ethnobotanical research conducted in East Africa. They were retrieved from several internet databases, including Google Scholar, Scopus, PubMed/Medline, Science Direct, and Research for Life. The study retrieved databases on plant families and species, plant parts used, preparation methods and routes of administration, and the country where the ethnobotanical field surveys were conducted. Graphs were produced using the GraphPad Prism 8.125 program (GraphPad Software, Inc., San Diego, CA). Tables and figures were used to present the data, which had been condensed into percentages and frequencies., Results: A total of 105 different plant species from 45 different plant families were identified, including Asteraceae (14), Euphorbiaceae (12), Musaceae (8), and Apocynaceae (7). Uganda registered the highest proportion (46% of the medicinal plants used). The most commonly mentioned medicinal plant species in cancer management was Prunus africana . Herbs (32%), trees and shrubs (28%), and leaves (45%) constituted the majority of herbal remedies. Most herbal remedies were prepared by boiling (decoction) and taken orally (57%)., Conclusion: East Africa is home to a wide variety of medicinal plant species that local populations and herbalists, or TMP, frequently use in the treatment of various types of cancer. The most frequently used families are Asteraceae and Euphorbiaceae, with the majority of species being found in Uganda. The most frequently utilized plant species is Prunus africana . Studies on the effectiveness of Prunus africana against other malignancies besides prostate cancer are required., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Context.—: Rapid onsite evaluation (ROSE) is critical in determining sample adequacy and triaging cytology samples. Although fine-needle aspiration biopsy (FNAB) is the primary method of initial tissue sampling in Tanzania, ROSE is not practiced., Objective.—: To investigate the performance of ROSE in determining cellular adequacy and providing preliminary diagnoses in breast FNAB in a low-resource setting., Design.—: Patients with breast masses were recruited prospectively from the FNAB clinic at Muhimbili National Hospital. Each FNAB was evaluated by ROSE for overall specimen adequacy, cellularity, and preliminary diagnosis. The preliminary interpretation was compared to the final cytologic diagnosis and histologic diagnosis, when available., Results.—: Fifty FNAB cases were evaluated, and all were adequate for diagnosis on ROSE and final interpretation. Overall percentage of agreement (OPA) between preliminary and final cytologic diagnosis was 84%, positive percentage of agreement (PPA) was 33%, and negative percentage of agreement (NPA) was 100% (κ = 0.4, P < .001). Twenty-one cases had correlating surgical resections. OPA between preliminary cytologic and histologic diagnoses was 67%, PPA was 22%, and NPA was 100% (κ = 0.2, P = .09). OPA between final cytologic and histologic diagnoses was 95%, PPA was 89%, and NPA was 100% (κ = 0.9, P = <.001)., Conclusions.—: False-positive rates of ROSE diagnoses for breast FNAB are low. While preliminary cytologic diagnoses had a high false-negative rate, final cytologic diagnoses had overall high concordance with histologic diagnoses. Therefore, the role of ROSE for preliminary diagnosis should be considered carefully in low-resource settings, and it may need to be paired with additional interventions to improve pathologic diagnosis., (© 2024 College of American Pathologists.)

Although the impact of host genetics on gut microbial diversity and the abundance of specific taxa is well established 1-6 , little is known about how host genetics regulates the genetic diversity of gut microorganisms. Here we conducted a meta-analysis of associations between human genetic variation and gut microbial structural variation in 9,015 individuals from four Dutch cohorts. Strikingly, the presence rate of a structural variation segment in Faecalibacterium prausnitzii that harbours an N-acetylgalactosamine (GalNAc) utilization gene cluster is higher in individuals who secrete the type A oligosaccharide antigen terminating in GalNAc, a feature that is jointly determined by human ABO and FUT2 genotypes, and we could replicate this association in a Tanzanian cohort. In vitro experiments demonstrated that GalNAc can be used as the sole carbohydrate source for F. prausnitzii strains that carry the GalNAc-metabolizing pathway. Further in silico and in vitro studies demonstrated that other ABO-associated species can also utilize GalNAc, particularly Collinsella aerofaciens. The GalNAc utilization genes are also associated with the host's cardiometabolic health, particularly in individuals with mucosal A-antigen. Together, the findings of our study demonstrate that genetic associations across the human genome and bacterial metagenome can provide functional insights into the reciprocal host-microbiome relationship., (© 2024. The Author(s).)

Background: In Uganda, medicinal plants have been utilized to treat a variety of ailments, including cancer. However, there is little information available about the medicinal plants used to treat cancer in the Elgon subregion. As a result, the current study documented the plant species used in the management of cancer in the Elgon sub-region., Methods: Data were gathered by observation, self-administered questionnaires, interview guides, and guided field trips. Analyzing descriptive statistics and creating graphs were done using SPSS (version 21.0) and GraphPad Prism® version 9.0.0, respectively. Well-established formulae were used to calculate quantitative indices. The narratives were interpreted using major theories and hypotheses in ethnobotany., Results: A total of 50 plant species from 36 families were documented, and herbal knowledge was mainly acquired through inheritance. Fabaceae and Asteraceae comprised more plant species used in herbal preparation. Most plants were collected from forest reserves (63%); herbal therapies were made from herbs (45%); and leaves were primarily decocted (43%). The most frequently used plants were Tylosema fassoglensis, Hydnora abyssinica, Azidarachata indica, Prunus Africana, Kigelia africana, Syzygium cumini, Hydnora africana, Rhoicissus tridentata, Albizia coriaria, and Plectranthus cuanneus. All the most commonly used plants exhibited a high preference ranking (60-86%) and reliability level (74.1-93.9%). Generally, the ICF for all the cancers treated by medicinal plants was close to 1 (0.84-0.95)., Conclusions: The ten most commonly utilized plants were favored, dependable, and most important for treating all known cancers. As a result, more investigation is required to determine their phytochemistry, toxicity, and effectiveness in both in vivo and in vitro studies. This could be a cornerstone for the pharmaceutical sector to develop new anticancer medications., (© 2023. The Author(s).)

Microaggressions between members of a team occur often in medicine, even despite good intentions. Such situations call for difficult conversations that restore inclusivity, diversity, and a healthy work culture. These conversations are often hard because of the unique background, experiences, and biases of each person. In medicine, skillful navigation of these interactions is paramount as it influences patient care and the workplace culture. Although much has been published about difficult interactions between providers and patients, significantly less information is available to help navigate provider-to-provider interactions, despite their critical role in improving multidisciplinary patient care teams and organizational environments. This article is intended to serve as a guide for medical professionals who are interested in taking personal responsibility for promoting a safe and inclusive culture by engaging in and modeling difficult conversations with colleagues. The article outlines important considerations to assist with intentional preparation and modulation of responses for all parties involved: conversation initiators, observers of the incident, and conversation receivers. Although these interactions are challenging, together as medical professionals we can approach each other with humility and compassion to achieve our ultimate goal of promoting humanity, not only for our patients but for ourselves and one another., Competing Interests: Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M23-1374.

Imaging tests are commonly used as an initial or early investigation for patients presenting with suspected acute gastrointestinal bleeding (AGIB). However, controversy remains regarding which of two frequently used modalities, computed tomography angiography (CTA) or technetium-99m labelled red blood cell scintigraphy (RBCS), is most accurate. This systematic review and meta-analysis was performed to compare the accuracy of CTA and RBCS for the detection and localization of AGIB. Five electronic databases were searched with additional manual searching of reference lists of relevant publications identified during the search. Two reviewers independently performed screening, data extraction and methodological assessments. Where appropriate, the bivariate model was used for meta-analysis of sensitivities and specificities for the detection of bleeding and Freeman-Tukey double-arcsine transformation used for meta-analysis of proportions of correctly localized bleeding sites. Forty-four unique primary studies were included: twenty-two investigating CTA, seventeen investigating RBCS and five investigating both modalities. Meta-analysis produced similar pooled sensitivities; 0.83 (95% CI 0.74-0.90) and 0.84 (0.68-0.92) for CTA and RBCS respectively. Pooled specificity for CTA was higher than RBCS; 0.90 (0.72-0.97) and 0.84 (0.71-0.91) respectively. However, differences were not statistically significant. CTA was superior to RBCS in correctly localizing bleeding; pooled proportions of 1.00 (0.98-1.00) and 0.90 (0.83-0.96) respectively (statistically significant difference, P < 0.001). There is no evidence that CTA and RBCS have different diagnostic performance with respect to the detection of AGIB. However, CTA is superior to RBCS in terms of correctly localising the bleeding site, supporting usage of CTA over RBCS as the first line imaging investigation., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Heart failure with preserved ejection fraction (HFpEF) has become the leading form of heart failure worldwide, particularly among elderly patient populations. HFpEF is associated with significant morbidity and mortality that may benefit from incorporation of palliative care (PC). Patients with HFpEF have similarly high mortality rates to patients with heart failure with reduced ejection fraction. PC trials for heart failure have shown improvement in quality of life, quality of death, and health care utilization, although most trials defined heart failure clinically without differentiating between HFpEF and heart failure with reduced ejection fraction. As such, the timing and role of PC for HFpEF care remains uncertain, and PC referral rates for HFpEF are very low despite potential improvements in important patient-centered outcomes. Specific barriers to referral include limited data, prognostic uncertainty, provider misconceptions about PC, inadequate specialty PC workforce, complexities of treating multimorbidity, and limited home care options for patients with heart failure. While there are many barriers to integration of PC into HFpEF care, there are multiple potential benefits to patients with HFpEF throughout their disease course. As this population continues to grow, targeted efforts to study and implement PC interventions are needed to improve patient quality of life and death., Competing Interests: Disclosures None.

Background: Expansive intracranial hematomas (EIH) following traumatic brain injury (TBI) continue to be a public health problem in Uganda. Data is limited regarding the neurosurgical outcomes of TBI patients. This study investigated the neurosurgical outcomes and associated risk factors of EIH among TBI patients at Mulago National Referral Hospital (MNRH)., Methods: A total of 324 subjects were enrolled using a prospective cohort study. Socio-demographic, risk factors and complications were collected using a study questionnaire. Study participants were followed up for 180 days. Univariate, multivariable, Cox regression analyses, Kaplan Meir survival curves, and log rank tests were sequentially conducted. P-values of < 0.05 at 95% Confidence interval (CI) were considered to be statistically significant., Results: Of the 324 patients with intracranial hematomas, 80.6% were male. The mean age of the study participants was 37.5 ± 17.4 years. Prevalence of EIH was 59.3% (0.59 (95% CI: 0.54 to 0.65)). Participants who were aged 39 years and above; PR = 1.54 (95% CI: 1.20 to 1.97; P = 0.001), and those who smoke PR = 1.21 (95% CI: 1.00 to 1.47; P = 0.048), and presence of swirl sign PR = 2.26 (95% CI: 1.29 to 3.95; P = 0.004) were found to be at higher risk for EIH. Kaplan Meier survival curve indicated that mortality at the 16-month follow-up was 53.4% (95% CI: 28.1 to 85.0). Multivariate Cox regression indicated that the predictors of mortality were old age, MAP above 95 mmHg, low GCS, complications such as infection, spasticity, wound dehiscence, CSF leaks, having GOS < 3, QoLIBRI < 50, SDH, contusion, and EIH., Conclusion: EIH is common in Uganda following RTA with an occurrence of 59.3% and a 16-month higher mortality rate. An increased age above 39 years, smoking, having severe systemic disease, and the presence of swirl sign are independent risk factors. Old age, MAP above 95 mmHg, low GCS, complications such as infection, spasticity, wound dehiscence, CSF leaks, having a GOS < 3, QoLIBRI < 50, ASDH, and contusion are predictors of mortality. These findings imply that all patients with intracranial hematomas (IH) need to be monitored closely and a repeat CT scan to be done within a specific period following their initial CT scan. We recommend the development of a protocol for specific surgical and medical interventions that can be implemented for patients at moderate and severe risk for EIH., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Cardiovascular disease (CVD) is the leading cause of death worldwide. Despite medical advances, patients with CVD experience high morbidity and mortality rates, affecting their quality of life and death. Among CVD conditions, palliative care has been studied mostly in patients with heart failure, where palliative care interventions have been associated with improvements in patient-centered outcomes, including quality of life, end-of-life care, and health care use. Although palliative care is now incorporated into the American Heart Association/American College of Cardiology/Heart Failure Society of America guidelines for heart failure, the role of palliative care for non-heart failure CVD remains uncertain. Across all causes of CVD, palliative care can play an important role in all domains of CVD care from initial diagnosis to terminal care. In addition to general cardiovascular palliative care practices applicable to all areas, disease-specific palliative care needs may warrant individualized palliative care models. In this review, we discuss the role of cardiovascular palliative care for ischemic heart disease, valvular disease, arrhythmias, peripheral artery disease, and adult congenital heart disease. Although there are multiple barriers to cardiovascular palliative care, we recommend a framework for studying and developing cardiovascular palliative care models to improve patient-centered goal-concordant care for this underserved patient population., Competing Interests: Disclosures None.

Non-communicable diseases (NCDs) are rising rapidly in urbanizing populations in sub-Saharan Africa. Assessment of inflammatory and metabolic characteristics of a urbanizing African population and the comparison with populations outside Africa could provide insight in the pathophysiology of the rapidly increasing epidemic of NCDs, including the role of environmental and dietary changes. Using a proteomic plasma profiling approach comprising 92 inflammation-related molecules, we examined differences in the inflammatory proteome in healthy Tanzanian and healthy Dutch adults. We show that healthy Tanzanians display a pro-inflammatory phenotype compared to Dutch subjects, with enhanced activity of the Wnt/β-catenin signalling pathway and higher concentrations of different metabolic regulators such as 4E-BP1 and fibroblast growth factor 21. Among the Tanzanian volunteers, food-derived metabolites were identified as an important driver of variation in inflammation-related molecules, emphasizing the potential importance of lifestyle changes. These findings endorse the importance of the current dietary transition and the inclusion of underrepresented populations in systems immunology studies., Competing Interests: GT, NV, VK, TP, PL, DC, JS, RK, LJ, Av, BM, MN, Qd No competing interests declared, (© 2023, Temba et al.)

A continuous viral inactivation (CVI) tubular reactor was designed for low pH viral inactivation within a continuous downstream system across multiple scales of operation. The reactors were designed to provide a minimum residence time of >60 min. The efficacy of this tubular reactor was tested with xenotropic murine leukemia virus (X-MuLV) through pulse injection experiments. It was determined that the minimum residence time of the small-scale reactor design, when operated at the target process flow rate, occurred between 63 and 67 min. Inactivation kinetics were compared between continuous operation and standard batch practices using three monoclonal antibodies. The quantification of the virus log reduction values (LRV) was similar between the two modes of operation and most of the acid-treated samples had virus concentrations below the limit of detection. However, residual infectivity was still present in the endpoint batch samples of two experiments while the continuous samples always remained below the limit of detection. This provides the foundation for leveraging a standard batch-based model to quantify the LRV for a CVI unit operation., (© 2022 Wiley Periodicals LLC.)

Background: Agricultural pesticides may exert strong selection pressures on malaria vectors during the aquatic life stages and may contribute to resistance in adult mosquitoes. This could reduce the performance of key vector control interventions such as indoor-residual spraying and insecticide-treated nets. The aim of this study was to investigate effects of agrochemicals on susceptibility and fitness of the malaria vectors across farming areas in Tanzania., Methods: An exploratory mixed-methods study was conducted to assess pesticide use in four villages (V1-V4) in south-eastern Tanzania. Anopheles gambiae (s.l.) larvae were collected from agricultural fields in the same villages and their emergent adults examined for insecticide susceptibility, egg-laying and wing lengths (as proxy for body size). These tests were repeated using two groups of laboratory-reared An. arabiensis, one of which was pre-exposed for 48 h to sub-lethal aquatic doses of agricultural pesticides found in the villages., Results: Farmers lacked awareness about the linkages between the public health and agriculture sectors but were interested in being more informed. Agrochemical usage was reported as extensive in V1, V2 and V3 but minimal in V4. Similarly, mosquitoes from V1 to V3 but not V4 were resistant to pyrethroids and either pirimiphos-methyl or bendiocarb, or both. Adding the synergist piperonyl butoxide restored potency of the pyrethroids. Pre-exposure of laboratory-reared mosquitoes to pesticides during aquatic stages did not affect insecticide susceptibility in emergent adults of the same filial generation. There was also no effect on fecundity, except after pre-exposure to organophosphates, which were associated with fewer eggs and smaller mosquitoes. Wild mosquitoes were smaller than laboratory-reared ones, but fecundity was similar., Conclusions: Safeguarding the potential of insecticide-based interventions requires improved understanding of how agricultural pesticides influence important life cycle processes and transmission potential of mosquito vectors. In this study, susceptibility of mosquitoes to public health insecticides was lower in villages reporting frequent use of pesticides compared to villages with little or no pesticide use. Variations in the fitness parameters, fecundity and wing length marginally reflected the differences in exposure to agrochemicals and should be investigated further. Pesticide use may exert additional life cycle constraints on mosquito vectors, but this likely occurs after multi-generational exposures., (© 2022. The Author(s).)

The modern cardiac intensive care unit (CICU) specializes in the care of a broad range of critically ill patients with both cardiac and non-cardiac serious illnesses. Despite advances, most conditions that necessitate CICU admission such as cardiogenic shock, continue to have a high burden of morbidity and mortality. The CICU often serves as the final destination for patients with end-stage disease, with one study reporting that one in five patients in the USA die in an intensive care unit (ICU) or shortly after an ICU admission. Palliative care is a broad subspecialty of medicine with an interdisciplinary approach that focuses on optimizing patient and family quality of life (QoL), decision-making, and experience. Palliative care has been shown to improve the QoL and symptom burden in patients at various stages of illness, however, the integration of palliative care in the CICU has not been well-studied. In this review, we outline the fundamental principles of high-quality palliative care in the ICU, focused on timeliness, goal-concordant decision-making, and family-centred care. We differentiate between primary palliative care, which is delivered by the primary CICU team, and secondary palliative care, which is provided by the consulting palliative care team, and delineate their responsibilities and domains. We propose clinical triggers that might spur serious illness communication and reappraisal of patient preferences. More research is needed to test different models that integrate palliative care in the modern CICU., (Published by Oxford University Press on behalf of European Society of Cardiology 2022. This work is written by (a) US Government employee(s) and is in the public domain in the US.)

Background: Geographic variability in coagulation across populations and their determinants are poorly understood., Objective: To compare thrombin (TG) and plasmin (PG) generation parameters between healthy Tanzanian and Dutch individuals, and to study associations with inflammation and different genetic, host and environmental factors., Methods: TG and PG parameters were measured in 313 Tanzanians of African descent living in Tanzania and 392 Dutch of European descent living in the Netherlands and related to results of a dietary questionnaire, circulating inflammatory markers, genotyping, and plasma metabolomics., Results: Tanzanians exhibited an enhanced TG and PG capacity, compared to Dutch participants. A higher proportion of Tanzanians had a TG value in the upper quartile with a PG value in the lower/middle quartile, suggesting a relative pro-coagulant state. Tanzanians also displayed an increased normalized thrombomodulin sensitivity ratio, suggesting reduced sensitivity to protein C. In Tanzanians, PG parameters (lag time and TTP) were associated with seasonality and food-derived plasma metabolites. The Tanzanians had higher concentrations of pro-inflammatory cytokines, which correlated strongly with TG and PG parameters. There was limited overlap in genetic variation associated with TG and PG parameters between the two cohorts. Pathway analysis of genetic variants in the Tanzanian cohort revealed multiple immune pathways that were enriched with TG and PG traits, confirming the importance of co-regulation between coagulation and inflammation., Conclusions: Tanzanians have an enhanced TG and PG potential compared to Dutch individuals, which may relate to differences in inflammation, genetics and diet. These observations highlight the importance of better understanding of the geographic variability in coagulation across populations., (© 2022 The Authors. Journal of Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis.)

Melatonin plays an important role in regulation and maintaining of the circadian rhythm. In the elderly population, an array of disturbances of circadian rhythm and sleep can be observed; however the current knowledge within the group of healthy, elderly is scarce. This systematic literature review of studies on the melatonin profile measured in the blood of healthy, elderly individuals included 519 studies, found in the primary search on PubMed. After reviewing the title and abstract, 47 studies were found eligible for full text review. The inclusion criteria were defined as follows: healthy, elderly individuals, with a mean or average age over 65 years and analysis done in blood or plasma. In addition to the primary search, three studies were directly identified by the reference lists of already included studies. A final total of 23 studies were included in the systematic literature review. In reviewing the literature, a clear circadian melatonin profile with a nocturnal peak at 3 am and lower daytime levels was observed in the healthy, elderly population. In elderly over 75 years of age, the nocturnal level of melatonin may be lower; however, the circadian rhythmicity is maintained. In the comparison of elderly, independently living individuals and individuals living in care facilities, the latter group had lower levels of nocturnal melatonin peak as well as higher daytime levels; however one can wonder if elderly in care facilities are healthy. The 23 included studies in the systematic literature review had varying primary objectives and generally the term "healthy" within this population group proves difficult to clearly define. As a result of this, an obvious interstudy variability existed, which is a limitation of this systematic literature review. However, the graphs depicted represent the best possible estimation of the melatonin profile in a healthy, elderly population. Future research in the melatonin profile within this population should focus on clearly defined healthy elderly to ensure a valid normal material in this age group.

Humans exhibit remarkable interindividual and interpopulation immune response variability upon microbial challenges. Cytokines play a vital role in regulating inflammation and immune responses, but dysregulation of cytokine responses has been implicated in different disease states. Host genetic factors were previously shown to significantly impact cytokine response heterogeneity mainly in European-based studies, but it is unclear whether these findings are transferable to non-European individuals. Here, we aimed to identify genetic variants modulating cytokine responses in healthy adults of East African ancestry from Tanzania. We leveraged both cytokine and genetic data and performed genome-wide cytokine quantitative trait loci (cQTLs) mapping. The results were compared with another cohort of healthy adults of Western European ancestry via direct overlap and functional enrichment analyses. We also performed meta-analyses to identify cQTLs with congruent effect direction in both populations. In the Tanzanians, cQTL mapping identified 80 independent suggestive loci and one genome-wide significant locus (TBC1D22A) at chromosome 22; SNP rs12169244 was associated with IL-1b release after Salmonella enteritidis stimulation. Remarkably, the identified cQTLs varied significantly when compared to the European cohort, and there was a very limited percentage of overlap (1.6% to 1.9%). We further observed ancestry-specific pathways regulating induced cytokine responses, and there was significant enrichment of the interferon pathway specifically in the Tanzanians. Furthermore, contrary to the Europeans, genetic variants in the TLR10-TLR1-TLR6 locus showed no effect on cytokine response. Our data reveal both ancestry-specific effects of genetic variants and pathways on cytokine response heterogeneity, hence arguing for the importance of initiatives to include diverse populations into genomics research., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2022 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.)

Context: Little is known about the real-time decision-making process of patients with capacity to choose withdrawal of temporary mechanical circulatory support (MCS)., Objectives: To assess how withdrawal of temporary MCS occurs when patients possess the capacity to make this decision themselves., Methods: This retrospective case series included adults supported by CentriMag Acute Circulatory Support or Veno-Arterial Extracorporeal Membrane Oxygenation from February 2, 2007 to May 27, 2020 at a tertiary academic medical center who possessed capacity to participate in end-of-life discussions. Authors performed chart review to determine times between "initiation of temporary MCS," "determination of 'bridge to nowhere,'" "patient expressing desire to withdraw," "agreement to withdraw," "withdrawal," and "death," as well as reasons for withdrawal and the role of ethics, psychiatry, and palliative care., Results: A total of 796 individuals were included. MCS was withdrawn in 178 (22.4%) of cases. Six of these 178 patients (3.4%) possessed the capacity to decide to withdraw MCS. Time between "patient expressing desire to withdraw" and "agreement to withdraw" ranged from 0 to 3 days; time between "agreement to withdraw" and "withdrawal" ranged from 0 to 6 days. Common reasons for withdrawal include perceived decline in quality of life or low probability of recovery. Ethics and psychiatry were consulted in 3 of 6 cases and palliative care in 5 of 6 cases., Conclusion: While it is rare for patients on MCS to request withdrawal, such cases provide insight into reasons for withdrawal and the important roles of multidisciplinary teams in helping patients and families through end-of-life decision-making., (Copyright © 2021 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Background: During the height of the coronavirus disease 2019 (COVID-19) pandemic in New York City, COVID-19 hospitalization was associated with high mortality. It is unknown how palliative care was utilized in this context. Objectives: To describe the frequency of palliative care consultation and its association with end-of-life care for deceased patients with COVID-19. Methods: Adults who were admitted to our institution between February 23, 2020, and April 21, 2020, and died from COVID-19 were included. The primary outcome was the frequency of palliative care consultation. Secondary analyses included the association of palliative care consultation with code status at the time of death, life-sustaining treatments, mechanical ventilation, invasive procedures, intensive care unit (ICU) admissions, and length of hospital stay. Results: The 203 patients were 61% male with median age 76 (interquartile range [IQR] 67-84) years. Palliative care was consulted for 113 patients (56%). At baseline, they were less independent in instrumental activities of daily living (28 patients, 26.1%, vs. 47 patients, 49.0%, p  < 0.01) and had more do-not-resuscitate orders (35 patients, 32.7%, vs. 11 patients, 11.5%, p  < 0.01). Palliative care consultation was associated with fewer invasive procedures (0, IQR 0-2, vs. 2, IQR 0-3, p  < 0.01), less mechanical ventilation (32 patients, 29.9% vs. 65 patients, 67.7%, p  < 0.01), and fewer ICU admissions (33 patients, 30.8% vs. 69 patients, 71.9%, p  < 0.01). Palliative care was associated with shorter ICU stays (0 days, IQR 0-4, vs. 4 days, IQR 0-12, p  < 0.01), whereas hospital stays did not differ significantly (8 days, IQR 5-12.5, vs. 10 days, IQR 5-16.3, p  = 0.15). Conclusion: Palliative care was consulted for roughly half of deceased patients with COVID-19 and those patients were less likely to undergo invasive procedures or life-sustaining treatments and spent less time in the ICU at the end of life.

Atherosclerosis is a chronic inflammatory disorder that is the underlying cause of most cardiovascular disease. Resident cells of the artery wall and cells of the immune system participate in atherogenesis. This process is influenced by plasma lipoproteins, genetics, and the hemodynamics of the blood flow in the artery. A variety of animal models have been used to study the pathophysiology and mechanisms that contribute to atherosclerotic lesion formation. No model is ideal as each has its own advantages and limitations with respect to manipulation of the atherogenic process and modeling human atherosclerosis and lipoprotein profile. In this chapter we will discuss pig and mouse models of experimental atherosclerosis. The similarity of pig lipoprotein metabolism and the pathophysiology of the lesions in these animals with that of humans is a major advantage. While a few genetically engineered pig models have been generated, the ease of genetic manipulation in mice and the relatively short time frame for the development of atherosclerosis has made them the most extensively used model. Newer approaches to induce hypercholesterolemia in mice have been developed that do not require germline modifications. These approaches will facilitate studies on atherogenic mechanisms., (© 2022. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

There is a growing literature on the impact of Covid-19 on commercial and labour conditions at suppliers in apparel global value chains (GVCs). Yet much less is known about the implications for suppliers operating in regional value chains (RVCs) in the global South. In this article, we focus on Eswatini, which has grown to become the largest African manufacturer and exporter of apparel to the region. We draw on a combination of firm-level export data and interviews with stakeholders before and after the Covid-19 lockdown to shed light on the influence of private and public governance on suppliers' economic and social upgrading and downgrading. We point to the coexistence of two separate private governance structures: the first characterised by direct contracts between South African retailers and large manufacturers ( direct suppliers ); the second operating through indirect purchasing via intermediaries from relatively smaller producers ( indirect suppliers ). While direct suppliers enjoyed higher levels of economic and social upgrading than indirect suppliers before Covid-19, the pandemic reinforced this division, with severe price cuts for indirect suppliers. Furthermore, while retailers provided some direct suppliers with support throughout the crisis, this was not the case for indirect suppliers, who remain comparatively more vulnerable. In terms of public governance, the negative consequences of the lockdown on firms' income and workers' livelihoods have been compounded by the state's ineffective response. Our paper contributes to the research on RVCs in the global South, enhancing our understanding of how different governance structures and external shocks affect firms' and workers' upgrading and downgrading prospects., (© The Author(s) 2021.)

The human gut microbiota is increasingly recognized as an important factor in modulating innate and adaptive immunity through release of ligands and metabolites that translocate into circulation. Urbanizing African populations harbor large intestinal diversity due to a range of lifestyles, providing the necessary variation to gauge immunomodulatory factors. Here, we uncover a gradient of intestinal microbial compositions from rural through urban Tanzanian, towards European samples, manifested both in relative abundance and genomic variation observed in stool metagenomics. The rural population shows increased Bacteroidetes, led by Prevotella copri, but also presence of fungi. Measured ex vivo cytokine responses were significantly associated with 34 immunomodulatory microbes, which have a larger impact on circulating metabolites than non-significant microbes. Pathway effects on cytokines, notably TNF-α and IFN-γ, differential metabolome analysis and enzyme copy number enrichment converge on histidine and arginine metabolism as potential immunomodulatory pathways mediated by Bifidobacterium longum and Akkermansia muciniphila., (© 2021. The Author(s).)

Context: As the use of venoarterial extracorporeal membrane oxygenation (VA-ECMO) increases, decisions regarding withdrawal from VA-ECMO increase., Objectives: To evaluate the clinical characteristics of patients withdrawn from VA-ECMO and the role of palliative care consultation in the decision., Methods: We retrospectively reviewed adult patients with cardiogenic shock requiring VA-ECMO at our institution, who were withdrawn from VA-ECMO between January 1, 2014 and May 31, 2019. The relationship between clinical characteristics and palliative care visits was assessed, and documented reasons for withdrawal were identified., Results: Of 460 patients who received VA-ECMO, 91 deceased patients (19.8%) were included. Forty-two patients (44.8%) had a palliative care consultation. The median duration on VA-ECMO was 4.0 days (interquartile range 8.8), and it was significantly longer for patients with palliative care consultation than those without (8.8 days vs. 2.0 days, P < 0.001). Among those with palliative care consultation, those with early consultation (within three days) had significantly shorter duration of VA-ECMO compared with those with late consultation (7.6 days vs. 13.5 days, t = 2.022, P = 0.008). Twenty-two (24.2%) had evidence of brain injury, which was significantly associated with patient age, number of comorbidities, duration of VA-ECMO, number of life-sustaining therapies, and number of palliative care visits (Wilks lambda 0.8925, DF 5,121, P = 0.016). Presence of brain injury was associated with fewer palliative care visits (t = 2.82, P = 0.006)., Conclusion: Shorter duration of VA-ECMO support and presence of brain injury were associated with fewer palliative care visits. Decisions around withdrawal of VA-ECMO support might be less complicated when patient's medical conditions deteriorate quickly or when neurological prognosis seems poor., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Sub-Saharan Africa currently experiences an unprecedented wave of urbanization, which has important consequences for health and disease patterns. This study aimed to investigate and integrate the immune and metabolic consequences of rural or urban lifestyles and the role of nutritional changes associated with urban living. In a cohort of 323 healthy Tanzanians, urban as compared to rural living was associated with a pro-inflammatory immune phenotype, both at the transcript and protein levels. We identified different food-derived and endogenous circulating metabolites accounting for these differences. Serum from urban dwellers induced reprogramming of innate immune cells with higher tumor necrosis factor production upon microbial re-stimulation in an in vitro model of trained immunity. These data demonstrate important shifts toward an inflammatory phenotype associated with an urban lifestyle and provide new insights into the underlying dietary and metabolic factors, which may affect disease epidemiology in sub-Sahara African countries.

We explore regions of parameter space that give rise to suppressed direct detection cross sections in a simple model of scalar dark matter with a scalar portal that mixes with the standard model Higgs. We found that even this simple model allows considerable room in the parameter space that has not been excluded by direct detection limits. A number of effects leading to this result have been previously noted. Our main new result explores interference effects between different contributions to DM annihilation when the DM mass is larger than the scalar portal mass. New annihilation channels open up and the parameters of the model need to compensate to give the correct DM relic abundance, resulting in smaller direct detection cross sections. We find that even in a very simple model of DM there are still sizeable regions of parameter space that are not ruled out by experiment., (© The Author(s) 2021.)

Purpose: Clinical breast examination (CBE) is one of the most common methods used for early detection of breast cancer in low- and middle-income countries. CBE alone is limited by lack of specificity and may result in unnecessary diagnostic procedures. We evaluated the feasibility of integrating CBE, fine-needle aspiration biopsy (FNAB), and rapid on-site evaluation (ROSE) in triaging palpable breast masses for specialized cancer care., Materials and Methods: An intensive breast cancer screening event was conducted at a national trade fair by a multidisciplinary team of care providers targeting a healthy population in Dar es Salaam, Tanzania. All adults age ≥ 18 years were invited to participate. CBE was performed by oncologists and/or pathologists. FNAB was performed by a pathologist on palpable masses that were then categorized as benign, indeterminate, or suspicious for malignancy or definitively malignant based on ROSE., Results: A total of 208 individuals (207 females, one male; median age, 36 years; range, 18-68 years) were screened. Most (90.8%, 189 of 208) had normal findings, whereas 7.2% (15 of 208), 1% (2 of 208), and 1% (2 of 208) had a palpable mass, breast pain, and nipple discharge, respectively. Two participants had lesions too small for palpation-guided biopsy and clinically consistent with fibroadenomas; the participants were counseled, and observation was recommended. FNAB was performed on 13 breast masses, with 9 of 13 (69%) categorized as benign and 4 of 13 (31%) suspicious for malignancy. Final cytopathologic review of referred patients confirmed one case to be breast adenocarcinoma, one was suggestive of fibroadenoma, and two showed inflammations., Conclusion: Integration of CBE with ROSE and FNAB was feasible in a breast cancer screening program in Tanzania. In settings with constrained resources for cancer care, this may be an effective method for triaging patients with breast masses.

Purpose of Review: Lipoproteins have significant role in both the promotion and prevention of atherosclerosis. This brief review will focus on recent reports on relationship between HDL and HDL subclasses and their composition and function, the role of apoC-III in metabolism of triglyceride-rich lipoproteins, the impact of Lipoprotein (a) (Lp(a)) on endothelial cells, and the mechanism of uptake of aggregated LDL by macrophages., Recent Findings: The complexity of the protein and lipid content of murine and human HDL and their relationship to its cholesterol efflux capacity have been examined. HDL has also been shown to have both antiatherogenic and proatherogenic properties. The relationship between apoC-III and LPL activity, apoprotein E mediated clearance of triglyceride-rich lipoproteins and the potential importance of apoC-III in the increased risk of cardiovascular disease in type 1 diabetics has been investigated. Oxidized phospholipid in Lp(a) promotes endothelial cells inflammatory and glycolytic responses. TLR4 participates in the uptake of aggregated LDL to contribute to foam cell formation., Summary: These studies contribute to our mechanistic understanding of how lipoproteins contribute to atherogenesis and identify potential therapeutic targets.

Objectives: The Motivational Thought Frequency (MTF) Scale has previously demonstrated a coherent four-factor internal structure (Intensity, Incentives Imagery, Self-Efficacy Imagery, Availability) in control of alcohol and effective self-management of diabetes. The current research tested the factorial structure and concurrent associations of versions of the MTF for increasing physical activity (MTF-PA) and reducing high-energy snacks (MTF-S)., Design: Study 1 examined the internal structure of the MTF-PA and its concurrent relationship with retrospective reports of vigorous physical activity. Study 2 attempted to replicate these results, also testing the internal structure of the MTF-S and examining whether higher MTF-S scores were found in participants scoring more highly on a screening test for eating disorder., Methods: In Study 1, 626 participants completed the MTF-PA online and reported minutes of activity in the previous week. In Study 2, 313 participants undertook an online survey that also included the MTF-S and the Eating Attitudes Test (EAT-26)., Results: The studies replicated acceptable fit for the four-factor structure on the MTF-PA and MTF-S. Significant associations of the MTF-PA with recent vigorous activity and of the MTF-S with EAT-26 scores were seen, although associations were stronger in Study 1., Conclusions: Strong preliminary support for both the MTF-PA and MTF-S was obtained, although more data on their predictive validity are needed. Associations of the MTF-S with potential eating disorder illustrate that high scores may not always be beneficial to health maintenance., (© 2020 The British Psychological Society.)

Natural antibodies (NAbs) are important regulators of tissue homeostasis and inflammation and are thought to have diverse protective roles in a variety of pathological states. E06 is a T15 idiotype IgM NAb exclusively produced by B-1 cells, which recognizes the phosphocholine (PC) head group in oxidized phospholipids on the surface of apoptotic cells and in oxidized LDL (OxLDL), and the PC present on the cell wall of Streptococcus pneumoniae . Here we report that titers of the E06 NAb are selectively increased several-fold in Cd1d -deficient mice, whereas total IgM and IgM antibodies recognizing other oxidation specific epitopes such as in malondialdehyde-modified LDL (MDA-LDL) and OxLDL were not increased. The high titers of E06 in Cd1d -deficient mice are not due to a global increase in IgM-secreting B-1 cells, but they are specifically due to an expansion of E06-secreting splenic B-1 cells. Thus, CD1d-mediated regulation appeared to be suppressive in nature and specific for E06 IgM-secreting cells. The CD1d-mediated regulation of the E06 NAb generation is a novel mechanism that regulates the production of this specific oxidation epitope recognizing NAb.

As rural African communities experience more frequent and extreme droughts, it is increasingly important that water supplies are climate resilient. Using a unique temporal dataset we explore rural water supply (n = 5196) performance during the 2015-16 drought in Ethiopia. Mean functionality ranged from 60% for motorised boreholes to 75% for hand-pumped boreholes. Real-time monitoring and responsive operation and maintenance led to rapid increases in functionality of hand-pumped and, to a lesser extent, motorised boreholes. Increased demand was placed on motorised boreholes in lowland areas as springs, hand-dug-wells and open sources failed. Most users travelled >1 h to access motorised boreholes but <30 min, increasing to 30-60 mins, for hand-pumped boreholes. Boreholes accessing deep (>30 m) groundwater performed best during the drought. Prioritising access to groundwater via multiple improved sources and a portfolio of technologies, such as hand-pumped and motorised boreholes, supported by responsive and proactive operation and maintenance, increases rural water supply resilience.