Mesopelagic fishes dominate otolith record of past two millennia in the Santa Barbara Basin.

The mesopelagic (200-1000 m) separates the productive upper ocean from the deep ocean, yet little is known of its long-term dynamics despite recent research that suggests fishes of this zone likely dominate global fish biomass and contribute to the downward flux of carbon. Here we show that mesopelagic fishes dominate the otolith (ear bone) record in anoxic sediment layers of the Santa Barbara Basin over the past two millennia. Among these mesopelagic fishes, otoliths from families Bathylagidae (deep-sea smelts) and Myctophidae (lanternfish) are most abundant. Otolith deposition rate fluctuates at decadal to centennial time scales and covaries with proxies for upper ocean temperature, consistent with climate forcing. Moreover, otolith deposition rate and proxies for temperature and primary productivity show contemporaneous discontinuities during the Medieval Climate Anomaly and Little Ice Age. Mesopelagic fishes may serve as proxies for future climatic influence at those depths including effects on the carbon cycle

Prevalence of chronic respiratory disease in urban and rural Uganda.

OBJECTIVE: To determine the prevalence of chronic respiratory diseases in urban and rural Uganda and to identify risk factors for these diseases. METHODS: The population-based, cross-sectional study included adults aged 35 years or older. All participants were evaluated by spirometry according to standard guidelines and completed questionnaires on respiratory symptoms, functional status and demographic characteristics. The presence of four chronic respiratory conditions was monitored: chronic obstructive pulmonary disease (COPD), asthma, chronic bronchitis and a restrictive spirometry pattern. FINDINGS: In total, 1502 participants (average age: 46.9 years) had acceptable, reproducible spirometry results: 837 (56%) in rural Nakaseke and 665 (44%) in urban Kampala. Overall, 46.5% (698/1502) were male. The age-adjusted prevalence of any chronic respiratory condition was 20.2%. The age-adjusted prevalence of COPD was significantly greater in rural than urban participants (6.1 versus 1.5%, respectively; P?<?0.001), whereas asthma was significantly more prevalent in urban participants: 9.7% versus 4.4% in rural participants (P?<?0.001). The age-adjusted prevalence of chronic bronchitis was similar in rural and urban participants (3.5 versus 2.2%, respectively; P?=?0.62), as was that of a restrictive spirometry pattern (10.9 versus 9.4%; P?=?0.82). For COPD, the population attributable risk was 51.5% for rural residence, 19.5% for tobacco smoking, 16.0% for a body mass index <?18.5 kg/m2 and 13.0% for a history of treatment for pulmonary tuberculosis. CONCLUSION: The prevalence of chronic respiratory disease was high in both rural and urban Uganda. Place of residence was the most important risk factor for COPD and asthma

Guanabenz repurposed as an antiparasitic with activity against acute and latent toxoplasmosis

Toxoplasma gondii is a protozoan parasite that persists as a chronic infection. Toxoplasma evades immunity by forming tissue cysts, which reactivate to cause life-threatening disease during immune suppression. There is an urgent need to identify drugs capable of targeting these latent tissue cysts, which tend to form in the brain. We previously showed that translational control is critical during infections with both replicative and latent forms of Toxoplasma. Here we report that guanabenz, an FDA-approved drug that interferes with translational control, has antiparasitic activity against replicative stages of Toxoplasma and the related apicomplexan parasite Plasmodium falciparum (a malaria agent). We also found that inhibition of translational control interfered with tissue cyst biology in vitro. Toxoplasma bradyzoites present in these abnormal cysts were diminished and misconfigured, surrounded by empty space not seen in normal cysts. These findings prompted analysis of the efficacy of guanabenz in vivo by using established mouse models of acute and chronic toxoplasmosis. In addition to protecting mice from lethal doses of Toxoplasma, guanabenz has a remarkable ability to reduce the number of brain cysts in chronically infected mice. Our findings suggest that guanabenz can be repurposed into an effective antiparasitic with a unique ability to reduce tissue cysts in the brain

Beyond birth-weight: early growth and adolescent blood pressure in a Peruvian population

Background. Longitudinal investigations into the origins of adult essential hypertension have found elevated blood pressure in children to accurately track into adulthood, however the direct causes of essential hypertension in adolescence and adulthood remains unclear.Methods. We revisited 152 Peruvian adolescents from a birth cohort tracked from 0 to 30 months of age, and evaluated growth via monthly anthropometric measurements between 1995 and 1998, and obtained anthropometric and blood pressure measurements 11–14 years later. We used multivariable regression models to study the effects of infantile and childhood growth trends on blood pressure and central obesity in early adolescence.Results. In regression models adjusted for interim changes in weight and height, each 0.1 SD increase in weight for length from 0 to 5 months of age, and 1 SD increase from 6 to 30 months of age, was associated with decreased adolescent systolic blood pressure by 1.3 mm Hg (95% CI −2.4 to −0.1) and 2.5 mm Hg (95% CI −4.9 to 0.0), and decreased waist circumference by 0.6 (95% CI −1.1 to 0.0) and 1.2 cm (95% CI −2.3 to −0.1), respectively. Growth in infancy and early childhood was not significantly associated with adolescent waist-to-hip ratio.Conclusions. Rapid compensatory growth in early life has been posited to increase the risk of long-term cardiovascular morbidities such that nutritional interventions may do more harm than good. However, we found increased weight growth during infancy and early childhood to be associated with decreased systolic blood pressure and central adiposity in adolescence

Addressing geographical variation in the progression of non-communicable diseases in Peru: the CRONICAS cohort study protocol

Background The rise in non-communicable diseases in developing countries has gained increased attention. Given that around 80% of deaths related to non-communicable diseases occur in low- and middle-income countries, there is a need for local knowledge to address such problems. Longitudinal studies can provide valuable information about disease burden of non-communicable diseases in Latin America to inform both public health and clinical settings. Methods The CRONICAS cohort is a longitudinal study performed in three Peruvian settings that differ by degree of urbanisation, level of outdoor and indoor pollution and altitude. The author sought to enrol an age- and sex-stratified random sample of 1000 participants at each site. Study procedures include questionnaires on socio-demographics and well-known risk factors for cardiopulmonary disease, blood draw, anthropometry and body composition, blood pressure and spirometry before and after bronchodilators. All participants will be visited at baseline, at 20 and 40 months. A random sample of 100 households at each site will be assessed for 24 h particulate matter concentration. Primary outcomes include prevalence of risk factors for cardiopulmonary diseases, changes in blood pressure and blood glucose over time and decline in lung function. Discussion There is an urgent need to characterise the prevalence and burden of non-communicable diseases in low- and middle-income countries. Peru is a middle-income country currently undergoing a rapid epidemiological transition. This longitudinal study will provide valuable information on cardiopulmonary outcomes in three different settings and will provide a platform to address potential interventions that are locally relevant or applicable to other similar settings in Latin America

Humidity and gravimetric equivalency adjustments for nephelometer-based particulate matter measurements of emissions from solid biomass fuel in cookstoves

Great uncertainty exists around indoor biomass burning exposure-disease relationships due to lack of detailed exposure data in large health outcome studies. Passive nephelometers can be used to estimate high particulate matter (PM) concentrations during cooking in low resource environments. Since passive nephelometers do not have a collection filter they are not subject to sampler overload. Nephelometric concentration readings can be biased due to particle growth in high humid environments and differences in compositional and size dependent aerosol characteristics. This paper explores relative humidity (RH) and gravimetric equivalency adjustment approaches to be used for the pDR-1000 used to assess indoor PM concentrations for a cookstove intervention trial in Nepal. Three approaches to humidity adjustment performed equivalently (similar root mean squared error). For gravimetric conversion, the new linear regression equation with log-transformed variables performed better than the traditional linear equation. In addition, gravimetric conversion equations utilizing a spline or quadratic term were examined. We propose a humidity adjustment equation encompassing the entire RH range instead of adjusting for RH above an arbitrary 60% threshold. Furthermore, we propose new integrated RH and gravimetric conversion methods because they have one response variable (gravimetric PM2.5 concentration), do not contain an RH threshold, and is straightforward

Indoor air pollution concentrations and cardiometabolic health across four diverse settings in Peru: a cross-sectional study.

BACKGROUND: Indoor air pollution is an important risk factor for health in low- and middle-income countries. METHODS: We measured indoor fine particulate matter (PM2.5) and carbon monoxide (CO) concentrations in 617 houses across four settings with varying urbanisation, altitude, and biomass cookstove use in Peru, between 2010 and 2016. We assessed the associations between indoor pollutant concentrations and blood pressure (BP), exhaled carbon monoxide (eCO), C-reactive protein (CRP), and haemoglobin A1c (HbA1c) using multivariable linear regression among all participants and stratifying by use of biomass cookstoves. RESULTS: We found high concentrations of indoor PM2.5 across all four settings (geometric mean ± geometric standard deviation of PM2.5 daily average in μg/m3): Lima 41.1 ± 1.3, Tumbes 35.8 ± 1.4, urban Puno 14.1 ± 1.7, and rural Puno 58.8 ± 3.1. High indoor CO concentrations were common in rural households (geometric mean ± geometric standard deviation of CO daily average in ppm): rural Puno 4.9 ± 4.3. Higher indoor PM2.5 was associated with having a higher systolic BP (1.51 mmHg per interquartile range (IQR) increase, 95% CI 0.16 to 2.86), a higher diastolic BP (1.39 mmHg higher DBP per IQR increase, 95% CI 0.52 to 2.25), and a higher eCO (2.05 ppm higher per IQR increase, 95% CI 0.52 to 3.57). When stratifying by biomass cookstove use, our results were consistent with effect measure modification in the association between PM2.5 and eCO: among biomass users eCO was 0.20 ppm higher per IQR increase in PM2.5 (95% CI - 2.05 to 2.46), and among non-biomass users eCO was 5.00 ppm higher per IQR increase in PM2.5 (95% CI 1.58 to 8.41). We did not find associations between indoor air concentrations and CRP or HbA1c outcomes. CONCLUSIONS: Excessive indoor concentrations of PM2.5 are widespread in homes across varying levels of urbanisation, altitude, and biomass cookstove use in Peru and are associated with worse BP and higher eCO

Validation of the Saint George's Respiratory Questionnaire in Uganda.

INTRODUCTION: Chronic obstructive pulmonary disease (COPD) will soon be the third leading global cause of death and is increasing rapidly in low/middle-income countries. There is a need for local validation of the Saint George's Respiratory Questionnaire (SGRQ), which can be used to identify those experiencing lifestyle impairment due to their breathing. METHODS: The SGRQ was professionally translated into Luganda and reviewed by our field staff and a local pulmonologist. Participants included a COPD-confirmed clinic sample and COPD-positive and negative members of the community who were enrolled in the Lung Function in Nakaseke and Kampala (LiNK) Study. SGRQs were assembled from all participants, while demographic and spirometry data were additionally collected from LiNK participants. RESULTS: In total, 103 questionnaires were included in analysis: 49 with COPD from clinic, 34 community COPD-negative and 20 community COPD-positive. SGRQ score varied by group: 53.5 for clinic, 34.4 for community COPD-positive and 4.1 for community COPD-negative (p<0.001). The cross-validated c statistic for SGRQ total score predicting COPD was 0.87 (95% CI 0.75 to 1.00). SGRQ total score was associated with COPD severity (forced expiratory volume in 1 s per cent of predicted), with an r coefficient of -0.60 (-0.75, -0.39). SGRQ score was associated with dyspnoea (OR 1.05/point; 1.01, 1.09) and cough (1.07; 1.03, 1.11). CONCLUSION: Our Luganda language SGRQ accurately distinguishes between COPD-positive and negative community members in rural Uganda. Scores were correlated with COPD severity and were associated with odds of dyspnoea and cough. We find that it can be successfully used as a respiratory questionnaire for obstructed adults in Uganda

Contribution of modifiable risk factors for hypertension and type-2 diabetes in Peruvian resource-limited settings.

BACKGROUND: It is important to understand the local burden of non-communicable diseases including within-country heterogeneity. The aim of this study was to characterise hypertension and type-2 diabetes profiles across different Peruvian geographical settings emphasising the assessment of modifiable risk factors. METHODS: Analysis of the CRONICAS Cohort Study baseline assessment was conducted. Cardiometabolic outcomes were blood pressure categories (hypertension, prehypertension, normal) and glucose metabolism disorder status (diabetes, prediabetes, normal). Exposures were study setting and six modifiable factors (smoking, alcohol drinking, leisure time and transport-related physical activity levels, TV watching, fruit/vegetables intake and obesity). Poisson regression models were used to report prevalence ratios (PR). Population attributable risks (PAR) were also estimated. RESULTS: Data from 3238 participants, 48.3% male, mean age 45.3 years, were analysed. Age-standardised (WHO population) prevalence of prehypertension and hypertension was 24% and 16%, whereas for prediabetes and type-2 diabetes it was 18% and 6%, respectively. Outcomes varied according to study setting (p<0.001). In multivariable model, hypertension was higher among daily smokers (PR 1.76), heavy alcohol drinkers (PR 1.61) and the obese (PR 2.06); whereas only obesity (PR 2.26) increased the prevalence of diabetes. PAR showed that obesity was an important determinant for hypertension (15.7%) and type-2 diabetes (23.9%). CONCLUSIONS: There is an evident heterogeneity in the prevalence of and risk factors for hypertension and diabetes within Peru. Prehypertension and prediabetes are highly prevalent across settings. Our results emphasise the need of understanding the epidemiology of cardiometabolic conditions to appropriately implement interventions to tackle the burden of non-communicable diseases