Total daily energy expenditure and elevated water turnover in a small-scale semi-nomadic pastoralist society from Northern Kenya.

BACKGROUND: Pastoralists live in challenging environments, which may be accompanied by unique activity, energy, and water requirements. AIM: Few studies have examined whether the demands of pastoralism contribute to differences in total energy expenditure (TEE) and water turnover (WT) compared to other lifestyles. SUBJECTS AND METHODS: Accelerometer-derived physical activity, doubly labelled water-derived TEE and WT, and anthropometric data were collected for 34 semi-nomadic Daasanach adults from three northern Kenyan communities with different levels of pastoralist activity. Daasanach TEEs and WTs were compared to those of other small-scale and industrialised populations. RESULTS: When modelled as a function of fat-free-mass, fat-mass, age, and sex, TEE did not differ between Daasanach communities. Daasanach TEE (1564-4172 kcal/day) was not significantly correlated with activity and 91% of TEEs were within the range expected for individuals from comparison populations. Mean WT did not differ between Daasanach communities; Daasanach absolute (7.54 litres/day men; 7.46 litres/day women), mass-adjusted, and TEE-adjusted WT was higher than most populations worldwide. CONCLUSIONS: The similar mass-adjusted TEE of Daasanach and industrialised populations supports the hypothesis that habitual TEE is constrained, with physically demanding lifestyles necessitating trade-offs in energy allocation. Elevated WT in the absence of elevated TEE likely reflects a demanding active lifestyle in a hot, arid climate.

Oxygen quenching of structurally characterized [5,10,15,20-tetrakis(4-fluoro-2,6-dimethylphenyl)porphyrinato]platinum(II).

The compound [5,10,15,20-tetrakis(4-fluoro-2,6-dimethylphenyl)porphyrinato]platinum(II), [Pt(C52H40F4N4)] or Pt(II)TFP, has been synthesized and structurally characterized by single-crystal X-ray crystallography. The Pt porphyrin exhibits a long-lived phosphorescent excited state (τ0 = 66 µs), which has been characterized by transient absorption and emission spectroscopy. The phosphorescence is extremely sensitive to oxygen, as reflected by a quenching rate constant of 5.0 × 108 M-1 s-1, and as measured by Stern-Volmer quenching analysis.

The effects of lifestyle change on indicators of cardiometabolic health in semi-nomadic pastoralists.

Background and objectives: Non-communicable disease risk and the epidemic of cardiometabolic diseases continue to grow across the expanding industrialized world. Probing the relationships between evolved human physiology and modern socioecological conditions is central to understanding this health crisis. Therefore, we investigated the relationships between increased market access, shifting subsistence patterns and cardiometabolic health indicators within Daasanach semi-nomadic pastoralists who vary in their engagement in traditional lifestyle and emerging market behaviors. Methodology: We conducted cross-sectional socioecological, demographic and lifestyle stressor surveys along with health, biomarker and nutrition examinations among 225 (51.6% female) Daasanach adults in 2019-2020. We used linear mixed-effects models to test how differing levels of engagement in market integration and traditional subsistence activities related to blood pressure (BP), body composition and blood chemistry. Results: We found that systolic and diastolic BP, as well as the probability of having high BP (hypertension), were negatively associated with distance to market, a proxy for market integration. Additionally, body composition varied significantly by socioeconomic status (SES), with significant positive associations between BMI and body fat and higher SES among adults. Conclusions and implications: While evidence for evolutionary mismatch and health variation have been found across a number of populations affected by an urban/rural divide, these results demonstrate the effects of market integration and sedentarization on cardiometabolic health associated with the early stages of lifestyle changes. Our findings provide evidence for the changes in health when small-scale populations begin the processes of sedentarization and market integration that result from myriad market pressures.

Early childhood growth in Daasanach pastoralists of Northern Kenya: Distinct patterns of faltering in linear growth and weight gain.

OBJECTIVES: Investigations of early childhood growth among small-scale populations are essential for understanding human life history variation and enhancing the ability to serve such communities through global public health initiatives. This study characterizes early childhood growth trajectories and identifies differences in growth patterns relative to international references among Daasanach semi-nomadic pastoralist children living in a hot, arid region of northern Kenya. METHODS: A large sample of height and weight measures were collected from children (N = 1756; total observations = 4508; age = 0-5 years) between 2018 and 2020. Daasanach growth was compared to international reference standards and Daasanach-specific centile growth curves and pseudo-velocity models were generated using generalized additive models for location scale and size. RESULTS: Compared to World Health Organization (WHO) reference, relatively few Daasanach children were stunted (14.3%), while a large proportion were underweight (38.5%) and wasted (53.6%). Additionally, Daasanach children had a distinctive pattern of growth, marked by an increase in linear growth velocity after 24 months of age and relatively high linear growth velocity throughout the rest of early childhood. CONCLUSIONS: These results identify a unique pattern of early childhood growth faltering among children in a small-scale population and may reflect a thermoregulatory adaptation to their hot, arid environment. As linear growth and weight gain remain important indicators of health, the results of this study provide insight into growth velocity variations. This study has important implications for global public health efforts to identify and address sources of early growth faltering and undernutrition in small-scale populations.

The co-occurrence of water insecurity and food insecurity among Daasanach pastoralists in northern Kenya.

OBJECTIVE: Water plays a critical role in the production of food and preparation of nutritious meals, yet few studies have examined the relationship between water and food insecurity. The primary objective of this study, therefore, was to examine how experiences of household water insecurity (HWI) relate to experiences of household food insecurity (HFI) among a pastoralist population living in an arid, water-stressed region of northern Kenya. DESIGN: We implemented the twelve-item Household Water Insecurity Experiences (HWISE, range 0-36) Scale and the nine-item Household Food Insecurity Access Scale (HFIAS, range 0-27) in a cross-sectional survey to measure HWI and HFI, respectively. Data on socio-demographic characteristics and intake of meat and dairy in the prior week were collected as covariates of interest. SETTING: Northern Kenya, June-July 2019. PARTICIPANTS: Daasanach pastoralist households (n 136) from seven communities. RESULTS: In the prior 4 weeks, 93·4 % and 98·5 % of households had experienced moderate-to-severe HWI and HFI, respectively. Multiple linear regression analyses indicated a strong association between HWI and HFI. Each point higher HWISE score was associated with a 0·44-point (95 % CI: 0·22, 0·66, P = 0·003) higher HFIAS score adjusting for socio-economic status and other covariates. CONCLUSIONS: These findings demonstrate high prevalence and co-occurrence of HWI and HFI among Daasanach pastoralists in northern Kenya. This study highlights the need to address HWI and HFI simultaneously when developing policies and interventions to improve the nutritional well-being of populations whose subsistence is closely tied to water availability and access.

Cross-cultural variation in thirst perception in hot-humid and hot-arid environments: Evidence from two small-scale populations.

OBJECTIVES: Thirst is an evolved central homeostatic feedback system that helps regulate body water for survival. Little research has examined how early development and exposure to extreme environments and water availability affect thirst perception, particularly outside Western settings. Therefore, we compared two indicators of perceived thirst (current thirst and pleasantness of drinking water) using visual scales among Tsimane' forager-horticulturalists in the hot-humid Bolivian Amazon and Daasanach agro-pastoralists in hot-arid Northern Kenya. METHODS: We examined how these measures of perceived thirst were associated with hydration status (urine specific gravity), ambient temperatures, birth season, age, and population-specific characteristics for 607 adults (n = 378 Tsimane', n = 229 Daasanach) aged 18+ using multi-level mixed-effect regressions. RESULTS: Tsimane' had higher perceived thirst than Daasanach. Across populations, hydration status was unrelated to both measures of thirst. There was a significant interaction between birth season and temperature on pleasantness of drinking water, driven by Kenya data. Daasanach born in the wet season (in utero during less water availability) had blunted pleasantness of drinking water at higher temperatures compared to those born in the dry season (in utero during greater water availability). CONCLUSIONS: Our findings suggest hydration status is not a reliable predictor of thirst perceptions in extreme-hot environments with ad libitum drinking. Rather, our findings, which require additional confirmation, point to the importance of water availability during gestation in affecting thirst sensitivity to heat and water feedback mechanisms, particularly in arid environments. Thirst regulation will be increasingly important to understand given climate change driven exposures to extreme heat and water insecurity.

Drinking water salinity is associated with hypertension and hyperdilute urine among Daasanach pastoralists in Northern Kenya.

Water salinity is a growing global environmental health concern. However, little is known about the relation between water salinity and chronic health outcomes in non-coastal, lean populations. Daasanach pastoralists living in northern Kenya traditionally rely on milk, yet are experiencing socioecological changes and have expressed concerns about the saltiness of their drinking water. Therefore, this cross-sectional study conducted water quality analyses to examine how water salinity, along with lifestyle factors like milk intake, was associated with hypertension (blood pressure BP ≥140 mm Hg systolic or ≥90 mm Hg diastolic) and hyperdilute urine (urine specific gravity <1.003 g/mL, indicative of altered kidney function). We collected health biomarkers and survey data from 226 non-pregnant adults (46.9% male) aged 18+ from 134 households in 2019 along with participant observations in 2020. The salinity (total concentration of all dissolved salts) of reported drinking water from hand-dug wells in dry river beds, boreholes, and a pond ranged from 120 to 520 mg/L. Water from Lake Turkana and standpipes, which was only periodically used for consumption when no other drinking sources are available, ranged from 1100 to 2300 mg/L. Multiple logistic regression models with standard errors clustered on households indicate that each additional 100 mg/L of drinking water salinity was associated with 45% (95% CI: 1.09-1.93, P = 0.010) increased odds of hypertension and 33% (95% CI: 0.97-1.83, P = 0.075) increased odds of hyperdilute urine adjusted for confounders. Results were robust to multiple specifications of the models and sensitivity analyses. Daily milk consumption was associated with 61-63% (P < 0.01) lower odds of both outcomes. This considerable protective effect of milk intake may be due to the high potassium, magnesium, and calcium contents or the protective lifestyle considerations of moving with livestock. Our study results demonstrate that drinking water salinity may have critical health implications for blood pressure and kidney function even among lean, active pastoralists.

Hydration in relation to water insecurity, heat index, and lactation status in two small-scale populations in hot-humid and hot-arid environments.

OBJECTIVES: This study compared the prevalence of concentrated urine (urine specific gravity ≥1.021), an indicator of hypohydration, across Tsimane' hunter-forager-horticulturalists living in hot-humid lowland Bolivia and Daasanach agropastoralists living in hot-arid Northern Kenya. It tested the hypotheses that household water and food insecurity would be associated with higher odds of hypohydration. METHODS: This study collected spot urine samples and corresponding weather data along with data on household water and food insecurity, demographics, and health characteristics among 266 Tsimane' households (N = 224 men, 235 women, 219 children) and 136 Daasanach households (N = 107 men, 120 women, 102 children). RESULTS: The prevalence of hypohydration among Tsimane' men (50.0%) and women (54.0%) was substantially higher (P < .001) than for Daasanach men (15.9%) and women (17.5%); the prevalence of hypohydration among Tsimane' (37.0%) and Daasanach (31.4%) children was not significantly different (P = .33). Multiple logistic regression models suggested positive but not statistically significant trends between household water insecurity and odds of hypohydration within populations, yet some significant joint effects of water and food insecurity were observed. Heat index (2°C) was associated with a 23% (95% confidence interval [CI]: 1.09-1.40, P = .001), 34% (95% CI: 1.18-1.53, P < .0005), and 23% (95% CI: 1.04-1.44, P = .01) higher odds of hypohydration among Tsimane' men, women, and children, respectively, and a 48% (95% CI: 1.02-2.15, P = .04) increase in the odds among Daasanach women. Lactation status was also associated with hypohydration among Tsimane' women (odds ratio = 3.35, 95% CI: 1.62-6.95, P = .001). CONCLUSION: These results suggest that heat stress and reproductive status may have a greater impact on hydration status than water insecurity across diverse ecological contexts.

Water turnover among human populations: Effects of environment and lifestyle.

OBJECTIVES: To discuss the environmental and lifestyle determinants of water balance in humans and identify the gaps in current research regarding water use across populations. METHODS: We investigated intraspecific variation in water turnover by comparing data derived from a large number of human populations measured using either dietary survey or isotope tracking. We also used published data from a broad sample of mammalian species to identify the interspecific relationship between body mass and water turnover. RESULTS: Water facilitates nearly all physiological tasks and water turnover is strongly related to body size among mammals (r2=0.90). Within humans, however, the effect of body size is small. Instead, water intake and turnover vary with lifestyle and environmental conditions. Notably, despite living physically active lives in conditions that should increase water demands, the available measures of water intake and turnover among small-scale farming and pastoralist communities are broadly similar to those in less active, industrialized populations. CONCLUSIONS: More work is required to better understand the environmental, behavioral, and cultural determinants of water turnover in humans living across a variety of ecosystems and lifestyles. The results of such work are made more vital by the climate crisis, which threatens the water security of millions around the globe.

Bortezomib-based antibody depletion for refractory autoimmune hematological diseases.

Certain patients with antibody-mediated autoimmune disease exhibit poor responses to conventional immunosuppression, including B-cell depletion with rituximab. Proteasome inhibitors such as bortezomib demonstrate pleiotropic immunomodulatory effects, including direct toxicity to antibody-producing cells. Here, we report preliminary evidence for the efficacy of bortezomib as salvage therapy for refractory autoimmune hematological disease. Thirteen treatment episodes in 10 patients with autoimmune hematological phenomena (autoimmune hemolytic anemia [AIHA; n = 8], acquired hemophilia (n = 1), immune thrombocytopenia (n = 1), and thrombotic thrombocytopenic purpura [TTP; n = 3]) and a median of 5 (range, 3-12) prior lines of therapy demonstrated an overall response rate of 77% (10 of 13) including 38% (5 of 13) complete remissions. The majority of clinical improvements were rapid, correlated with biomarkers of autoantibody reduction, and were associated with an acceptable safety profile. Responses appeared durable following treatment of TTP and acquired hemophilia; AIHA responses were more limited with a pattern of relapse following bortezomib cessation. These data provide proof of concept for the utility of proteasome inhibition as antibody depletion therapy in autoimmune disease.

Magnetars: the physics behind observations. A review.

Magnetars are the strongest magnets in the present universe and the combination of extreme magnetic field, gravity and density makes them unique laboratories to probe current physical theories (from quantum electrodynamics to general relativity) in the strong field limit. Magnetars are observed as peculiar, burst-active x-ray pulsars, the anomalous x-ray pulsars (AXPs) and the soft gamma repeaters (SGRs); the latter emitted also three 'giant flares', extremely powerful events during which luminosities can reach up to 10(47) erg s(-1) for about one second. The last five years have witnessed an explosion in magnetar research which has led, among other things, to the discovery of transient, or 'outbursting', and 'low-field' magnetars. Substantial progress has been made also on the theoretical side. Quite detailed models for explaining the magnetars' persistent x-ray emission, the properties of the bursts, the flux evolution in transient sources have been developed and confronted with observations. New insight on neutron star asteroseismology has been gained through improved models of magnetar oscillations. The long-debated issue of magnetic field decay in neutron stars has been addressed, and its importance recognized in relation to the evolution of magnetars and to the links among magnetars and other families of isolated neutron stars. The aim of this paper is to present a comprehensive overview in which the observational results are discussed in the light of the most up-to-date theoretical models and their implications. This addresses not only the particular case of magnetar sources, but the more fundamental issue of how physics in strong magnetic fields can be constrained by the observations of these unique sources.

Thrombin-dependent intravascular leukocyte trafficking regulated by fibrin and the platelet receptors GPIb and PAR4.

Thrombin is a central regulator of leukocyte recruitment and inflammation at sites of vascular injury, a function thought to involve primarily endothelial PAR cleavage. Here we demonstrate the existence of a distinct leukocyte-trafficking mechanism regulated by components of the haemostatic system, including platelet PAR4, GPIbα and fibrin. Utilizing a mouse endothelial injury model we show that thrombin cleavage of platelet PAR4 promotes leukocyte recruitment to sites of vascular injury. This process is negatively regulated by GPIbα, as seen in mice with abrogated thrombin-platelet GPIbα binding (hGPIbα(D277N)). In addition, we demonstrate that fibrin limits leukocyte trafficking by forming a physical barrier to intravascular leukocyte migration. These studies demonstrate a distinct 'checkpoint' mechanism of leukocyte trafficking involving balanced thrombin interactions with PAR4, GPIbα and fibrin. Dysregulation of this checkpoint mechanism is likely to contribute to the development of thromboinflammatory disorders.

Platelets are not just for clots.

Although the role of platelets as central mediators of hemostasis and thrombosis has been the primary focus of research into platelet biology for more than a century, over the last decade, nonhemostatic functions of platelets have been increasingly defined. As such, a large body of experimental evidence now exists, which places the platelet as a key player in mediating a diverse range of immune, inflammatory, and malignant disease processes. This review outlines the central mechanisms that underpin the nonhemostatic role of platelets and provides a summary of evidence demonstrating a role for platelets in mediating selected inflammatory, immune, and malignant disease processes.

Retinal architecture and mfERG: Optic nerve head component response characteristics in MS.

OBJECTIVE: To describe a novel neurophysiologic signature of the retinal ganglion cell and to elucidate its relationship to abnormalities in validated structural and functional measures of the visual system. METHODS: We used multifocal electroretinogram-generated optic nerve head component (ONHC) responses from normal subjects (n = 18), patients with multiple sclerosis (MS) (n = 18), and those with glaucoma (n = 3). We then characterized the relationship between ONHC response abnormalities and performance on low-contrast visual acuity, multifocal visual-evoked potential-induced cortical responses, and average and quadrant retinal nerve fiber layer (RNFL) thicknesses, as measured by spectral-domain optical coherence tomography. RESULTS: Compared with the eyes of normal subjects, the eyes of patients with MS exhibited an increased number of abnormal or absent ONHC responses (p < 0.0001). For every 7-letter reduction in low-contrast letter acuity, there were corresponding 4.6 abnormal ONHC responses at 2.5% contrast (p < 0.0001) and 6.6 abnormalities at the 1.25% contrast level (p < 0.0001). Regarding average RNFL thickness, for each 10-µm thickness reduction, we correspondingly observed 6.8 abnormal ONHC responses (p = 0.0002). The most robust association was between RNFL thinning in the temporal quadrant and ONHC response abnormalities (p < 0.0001). CONCLUSION: Further characterization of ONHC abnormalities (those that are reversible and irreversible) may contribute to the development of novel neurotherapeutic strategies aimed at achieving neuroprotective, and perhaps even neurorestorative, effects in disorders that target the CNS in general, and MS in particular.

The CXCR1/2 ligand NAP-2 promotes directed intravascular leukocyte migration through platelet thrombi.

Thrombosis promotes leukocyte infiltration into inflamed tissues, leading to organ injury in a broad range of diseases; however, the mechanisms by which thrombi guide leukocytes to sites of vascular injury remain ill-defined. Using mouse models of endothelial injury (traumatic or ischemia reperfusion), we demonstrate a distinct process of leukocyte recruitment, termed "directed intravascular migration," specifically mediated by platelet thrombi. Single adherent platelets and platelet aggregates stimulated leukocyte shape change at sites of endothelial injury; however, only thrombi were capable of inducing directed intravascular leukocyte migration. Leukocyte recruitment and migration induced by platelet thrombi occurred most prominently in veins but could also occur in arteries following ischemia-reperfusion injury. In vitro studies demonstrated a major role for platelet-derived NAP-2 (CXCL-7) and its CXCR1/2 receptor in regulating leukocyte polarization and motility. In vivo studies demonstrated the presence of an NAP-2 chemotactic gradient within the thrombus body. Pharmacologic blockade of CXCR1/2 as well as genetic deletion of NAP-2 markedly reduced leukocyte shape change and intrathrombus migration. These studies define a distinct process of leukocyte migration that is initiated by homotypic adhesive interactions between platelets, leading to the development of an NAP-2 chemotactic gradient within the thrombus body that guides leukocytes to sites of vascular injury.

Electroconvulsive therapy improves persistent psychosis after repeated use of methylenedioxypyrovalerone ("bath salts").

The use of synthetic cathinone drugs, known popularly as "bath salts," may lead to persistent visual hallucinations and paranoia with repeated use. This is the first case report known to the authors suggesting that such symptoms may persist despite discontinuing the use of psychoactive bath salts. As is the case with other such symptoms associated with use of stimulant drugs of abuse, these symptoms are resistant to pharmacologic treatment, and electroconvulsive therapy can be a useful treatment modality in such situations. This report adds to evidence for efficacy of electroconvulsive therapy in the management of stimulant-induced persistent psychotic symptoms.