Rats lacking Ucp1 present a novel translational tool for the investigation of thermogenic adaptation during cold challenge.

AIM: Valuable studies have tested the role of UCP1 on body temperature maintenance in mice, and we sought to knockout Ucp1 in rats (Ucp1-/- ) to provide insight into thermogenic mechanisms in larger mammals. METHODS: We used CRISPR/Cas9 technology to create Ucp1-/- rats. Body weight and adiposity were measured, and rats were subjected to indirect calorimetry. Rats were maintained at room temperature or exposed to 4°C for either 24 h or 14 days. Analyses of brown and white adipose tissue and skeletal muscle were conducted via histology, western blot comparison of oxidative phosphorylation proteins, and qPCR to compare mitochondrial DNA levels and mRNA expression profiles. RNA-seq was performed in skeletal muscle. RESULTS: Ucp1-/- rats withstood 4°C for 14 days, but core temperature steadily declined. All rats lost body weight after 14 days at 4°C, but controls increased food intake more robustly than Ucp1-/- rats. Brown adipose tissue showed signs of decreased activity in Ucp1-/- rats, while mitochondrial lipid metabolism markers in white adipose tissue and skeletal muscle were increased. Ucp1-/- rats displayed more visible shivering and energy expenditure than controls at 4°C. Skeletal muscle transcriptomics showed more differences between genotypes at 23°C than at 4°C. CONCLUSION: Room temperature presented sufficient cold stress to rats lacking UCP1 to activate compensatory thermogenic mechanisms in skeletal muscle, which were only activated in control rats following exposure to 4°C. These results provide novel insight into thermogenic responses to UCP1 deficiency; and highlight Ucp1-/- rats as an attractive translational model for the study of thermogenesis.

Association between toxocariasis seropositivity and serointensity and cognitive function in older U.S. adults.

The nematodes Toxocara canis (Werner, 1782) and Toxocara cati (Schrank, 1788) have been associated with worse human cognitive function in children and middle-aged adults. In this study, we sought to determine the association between Toxocara seropositivity and serointensity determined by detection of IgG antibodies against the Toxocara antigen recombinant Tc-CTL-1 and cognitive function in older adults, including approximately 1,350 observations from the 2013-2014 National Health and Nutrition Examination Survey. Mean fluorescence intensity was used to quantify IgG antibodies against the Toxocara recombinant Tc-CTL-1 antigen, and respondents were considered positive at values greater than 23.1. In adjusted models from sample sizes ranging from 1,274 to 1,288 depending on the individual cognitive task, we found that Toxocara seropositivity was associated with worse performance on the animal-fluency task (b = -1.245, 95% CI: -2.392 to -0.099, P< 0.05) and the digit-symbol coding task (b = -5.159, 95% CI: -8.337 to -1.980, P< 0.001). Toxocara serointensity assessed using log-transformed mean fluorescence intensity as a continuous variable was associated with worse performance on the digit-symbol coding task (b = -1.880, 95% CI: -2.976 to -0.783, P < 0.001). There were no significant associations with tasks assessing memory. Further, age modified the association between Toxocara and cognitive function, although sex, educational attainment, and income did not. These findings suggest that Toxocara might be associated with deficits in executive function and processing speed in older U.S. adults, although additional research is required to better describe cognitive function in older adults who are seropositive for Toxocara spp.

Female Mice Are Protected from Metabolic Decline Associated with Lack of Skeletal Muscle HuR.

Male mice lacking HuR in skeletal muscle (HuRm-/-) have been shown to have decreased gastrocnemius lipid oxidation and increased adiposity and insulin resistance. The same consequences have not been documented in female HuRm-/- mice. Here we examine this sexually dimorphic phenotype. HuRm-/- mice have an increased fat mass to lean mass ratio (FM/LM) relative to controls where food intake is similar. Increased body weight for male mice correlates with increased blood glucose during glucose tolerance tests (GTT), suggesting increased fat mass in male HuRm-/- mice as a driver of decreased glucose clearance. However, HuRm-/- female mice show decreased blood glucose levels during GTT relative to controls. HuRm-/- mice display decreased palmitate oxidation in skeletal muscle relative to controls. This difference is more robust for male HuRm-/- mice and more exaggerated for both sexes at high dietary fat. A high-fat diet stimulates expression of Pgc1α in HuRm-/- male skeletal muscle, but not in females. However, the lipid oxidation Pparα pathway remains decreased in HuRm-/- male mice relative to controls regardless of diet. This pathway is only decreased in female HuRm-/- mice fed high fat diet. A decreased capacity for lipid oxidation in skeletal muscle in the absence of HuR may thus be linked to decreased glucose clearance in male but not female mice.

The Extended Role of Health Facility Cleaners in Maternity Care in Kenya.

CONTEXT: A growing body of evidence indicates that nonclinical health care facility staff provide support beyond their traditional roles, particularly in low- and middle-income countries. It is important to examine the role of health facility cleaners in Kenya-from their perspective-to better understand their actual and perceived responsibilities in maternity care. METHODS: In-depth, face-to-face interviews using a semistructured guide were conducted with 14 cleaners working at three public health facilities in Nairobi and Kiambu Counties, Kenya, in August and September 2016. Results were coded and categorized using a thematic content analysis approach. RESULTS: Cleaners reported performing a range of services beyond typical maintenance responsibilities, including providing emotional, informational and instrumental support to maternity patients. They described feeling disrespected when patients were untidy or experienced bleeding; however, such examples revealed cleaners' need to better understand labor and childbirth processes. Cleaners also indicated a desire for training on interpersonal skills to improve their interactions with patients. CONCLUSION: Cleaners' direct involvement in maternity patients' care is an alarming symptom of overburdened health facilities, insufficient staffing and inadequate training. This key yet overlooked cadre of health care staff deserves appropriate support and further research to understand and alleviate health system shortcomings, and to improve the quality of maternity health care provision.

RESUMEN Contexto: Un creciente conjunto de evidencia indica que miembros del personal no clínico de las instituciones de salud proporcionan apoyos que trascienden sus roles tradicionales, particularmente en países de bajos y medianos ingresos. Es importante examinar el rol del personal de limpieza de las instituciones de salud en Kenia­desde su perspectiva­para comprender mejor sus responsabilidades reales y percibidas en cuanto a la atención materna. Métodos: Se condujeron entrevistas personales en profundidad utilizando una guía semiestructurada con 14 miembros del personal de limpieza que trabajaban en tres instituciones de salud pública en los condados de Nairobi y Kiambu, Kenia, en agosto y septiembre de 2016. Los resultados fueron codificados y categorizados mediante un enfoque de análisis de contenido temático. Resultados: El personal de limpieza reportó que realizaba una variedad de servicios además de sus responsabilidades típicas de mantenimiento, que incluyeron la provisión de apoyo emocional, informativo e instrumental a las pacientes de maternidad. Describieron un sentimiento de falta de respeto cuando las pacientes estaban desaseadas o experimentaban sangrado; sin embargo, tales ejemplos revelaron la necesidad de que el personal de limpieza comprendiera mejor los procesos de trabajo de parto y parto. El personal de limpieza también indicó su deseo de recibir capacitación en habilidades interpersonales para mejorar su interacción con las mujeres. Conclusión: La participación directa del personal de limpieza en la atención a pacientes de maternidad es un síntoma alarmante de sobrecarga de las instituciones de salud, de personal insuficiente y de capacitación inadecuada. Este grupo de personal de atención a la salud, clave pero ignorado, merece apoyo apropiado y se necesita mayor investigación para comprender y mitigar los defectos del sistema de salud y mejorar la calidad de la prestación de servicios de salud materna.

RÉSUMÉ Contexte: La documentation et les données indiquent de plus en plus que le travail du personnel non clinique des structures de soins de santé s'étend au-delà du rôle qu'on attendrait ordinairement de lui, en particulier dans les pays à revenu faible ou intermédiaire. Il importe d'examiner ­ de leur point de vue ­ le rôle des effectifs de nettoyage des structures sanitaires du Kenya si l'on veut mieux comprendre leurs responsabilités réelles et perçues dans les soins de maternité. Méthodes: Des entretiens en personne approfondis, suivant un guide semi-structuré, ont été menés avec 14 membres du personnel de nettoyage de trois structures sanitaires de l'État dans les comtés de Nairobi et de Kiambu (Kenya), en août et septembre 2016. Les résultats ont été codés et catégorisés selon une approche d'analyse de contenu thématique. Résultats: Le personnel de nettoyage interrogé a déclaré effectuer des services allant au-delà des responsabilités d'entretien types, y compris l'apport d'un soutien affectif, informatif et matériel aux patientes des services de maternité. Il estimait subir un manque de respect lorsque les patientes présentaient une allure peu soignée ou saignaient. Ces exemples révèlent cependant la nécessité pour le personnel de nettoyage de mieux comprendre les processus du travail et de l'accouchement. Le personnel interrogé a également exprimé un désir de formation en matière de compétences interpersonnelles, en vue d'une meilleure interaction avec les femmes. Conclusion: La participation directe du personnel de nettoyage aux soins de maternité des patientes représente un symptôme alarmant de structures sanitaires surchargées, d'effectifs insuffisants et de formation inadéquate. Cette catégorie d'effectifs sanitaires, essentielle mais généralement négligée, mérite un soutien approprié. Une recherche approfondie doit être entreprise pour comprendre et combler les lacunes du système de santé et pour améliorer la qualité de prestation des soins de maternité.

The RNA binding protein HuR influences skeletal muscle metabolic flexibility in rodents and humans.

BACKGROUND: Metabolic flexibility can be assessed by changes in respiratory exchange ratio (RER) following feeding. Though metabolic flexibility (difference in RER between fasted and fed state) is often impaired in individuals with obesity or type 2 diabetes, the cellular processes contributing to this impairment are unclear. MATERIALS AND METHODS: From several clinical studies we identified the 16 most and 14 least metabolically flexible male and female subjects out of >100 participants based on differences between 24-hour and sleep RER measured in a whole-room indirect calorimeter. Global skeletal muscle gene expression profiles revealed that, in metabolically flexible subjects, transcripts regulated by the RNA binding protein, HuR, are enriched. We generated and characterized mice with a skeletal muscle-specific knockout of the HuR encoding gene, Elavl1 (HuRm-/-). RESULTS: Male, but not female, HuRm-/- mice exhibit metabolic inflexibility, with mild obesity, impaired glucose tolerance, impaired fat oxidation and decreased in vitro palmitate oxidation compared to HuRfl/fl littermates. Expression levels of genes involved in mitochondrial fatty acid oxidation and oxidative phosphorylation are decreased in both mouse and human muscle when HuR is inhibited. CONCLUSIONS: HuR inhibition results in impaired metabolic flexibility and decreased lipid oxidation, suggesting a role for HuR as an important regulator of skeletal muscle metabolism.

Toxocara Seroprevalence and Associated Risk Factors in the United States.

Caused by the parasitic nematodes Toxocara canis and cati, toxocariasis in humans can result in covert toxocariasis, ocular toxocariasis, visceral larval migrans, and neurotoxocariasis. A common infection, toxocariasis exposure varies widely within and between countries, with a previous estimate of Toxocara seroprevalence using data from 1988 to 1994 in the United States of approximately 13%. Age, poverty, sex, educational attainment, ethnicity, and region have been associated with Toxocara seroprevalence. In this study, we sought to determine the seroprevalence of and factors associated with Toxocara seropositivity in the United States using data from the National Health and Nutrition Examination Survey from 2011 to 2014 to provide a more recent estimate of Toxocara seroprevalence in the United States. We found an overall Toxocara seroprevalence of 5.1%. Increasing age, male sex, low educational attainment, low income, and immigration status each was associated with Toxocara seropositivity. Mexican Americans had reduced odds of exposure. These findings show that exposure to Toxocara continues in the United States and that several demographic factors influence the risk of exposure.

A time-use study of community health worker service activities in three rural districts of Tanzania (Rufiji, Ulanga and Kilombero).

BACKGROUND: Despite expanding international commitment to community health worker (CHW) deployment, little is known about how such workers actually use their time. This paper investigates this issue for paid CHWs named "Community Health Agents," which in Swahili is "Wawezeshaji wa Afya ya Jamii" ("WAJA"), trained for 9 months in primary health care service delivery and deployed to villages as subjects of a randomized trial of their impact on childhood survival in three rural districts of Tanzania. METHODS: To capture information about time allocation, 30 WAJA were observed during conventional working hours by research assistants for 5 days each over a period of 4 weeks. Results were presented in term of percentage time allocation for direct client treatment, documentation activities, health education, health promotion non-work-related activities and personal activities. RESULTS: During routine 8-h workdays, 59.5 % of WAJA time was spent on the provision of health services and other work-related activities. Overall, WAJA spent 27.8 % of their work on traveling from home to home, 33.1 % on health education, 9.9 % of health promotion and only 12.3 % on direct patient care. Other activities related to documentation (7.8 %) and supervision (2.5 %). CONCLUSIONS: Results reflect the pressing obligations of WAJA to engage in activities other than direct work responsibilities during routine work hours. Time spent on work activities is primarily used for health education, promotion, moving between households, and direct patient care. However, greater effort should be directed to strengthening supervisory systems and follow-up of challenges WAJAs facing in order to increase proportion of working hours.

A qualitative analysis of the effect of a community-based primary health care programme on reproductive preferences and contraceptive use among the Kassena-Nankana of northern Ghana.

BACKGROUND: In 2000, Ghana launched the Community-based Health Planning and Services (CHPS) initiative to improve access to health and family planning services. This initiative was based in part on research, known as the Navrongo Project, conducted in the Kassena-Nankana district (KND) between 1994 to 2003 which demonstrated significant impact on fertility and child mortality. This paper examines current contraceptive perceptions in communities that were exposed to the Project's service models over the 1994 to 2003 period, and the post-experimental policies of the CHPS era. METHODS: Qualitative study was conducted in the KND of Ghana from June to September, 2012, by convening 8 male and 8 female FGD panels as well as 8 in-depth interviews of community leaders. Data collection was stratified by original experimental cell of the Navrongo Project to permit appraisal of social effects of contrasting experimental conditions. Inductive content analysis was performed with QSR Nvivo 10 to identify predominant themes. RESULTS: While findings show that exposure to community-based services was associated with enhanced approval of birth spacing and limitation, this view is grounded in perceptions that childhood survival has improved. Nonetheless, concerns were expressed about contraceptive side effects, prominently permanent sterility. Strategies for male outreach and community engagement originally introduced during the Navrongo Project have not been sustained with CHPS scale-up. The apparent atrophy of attention to the needs of men may explain the resistance of some males to the notion of female reproductive autonomy and the practice of some women to adopt contraception in secret. Despite this apparent programmatic dearth of male engagement, there is evidence to suggest that social impact of the original male engagement strategy persists in communities where male mobilization was combined with doorstep provision of family planning care during the Navrongo Project. CONCLUSION: Community-based services fostered attitudinal change towards family planning in a traditional sub-Saharan African setting. Sustained exposure to primary health care that have improved the survival of children has made the use of contraception more acceptable. Efforts should be embedded in primary health care programmes that address concerns about child survival while also consigning sustained priority to the information needs of men.

Factors facilitating and constraining the scaling up of an evidence-based strategy of community-based primary care: management perspectives from northern Ghana.

From 1994 to 2003, the government of Ghana investigated the child survival and fertility impacts of community-based primary care nurses and volunteer mobilisation efforts. This study, known as the Navrongo Project, demonstrated improved health outcomes and was scaled-up as the Community-based Health Planning and Services (CHPS) Initiative. Studies suggest that scaled-up CHPS services have not fully replicated the impact of the Project. This study investigates implementation challenges that could explain this atrophy by assembling the perspectives of health care managers that have experience with both the Project and CHPS. Data from in-depth interviews of health managers are analysed using deductive content analysis. Respondents exhibited a consistent vision of doorstep services with regard to the Project and CHPS. They shared the perspective that while scale-up has progressed slowly, it has expanded the range of services provided. Respondents felt, however, that the original emphasis on community involvement has atrophied with scale-up and that current operations are managed less rigorously than during the Project. Thus, while the expanded scope of CHPS has increased access to health care, the original focus on community engagement has faded. The original Project leadership strategy merits review for ways to integrate leadership development into scale-up activities.

A comparative qualitative study of misconceptions associated with contraceptive use in southern and northern ghana.

Evidence from Ghana consistently shows that unmet need for contraception is pervasive with many possible causes, yet how these may differ by cultural zone remains poorly understood. This qualitative study was designed to elicit information on the nature and form of misconceptions associated with contraceptive use among northern and southern Ghanaians. Twenty-two focus group discussions (FGDs) with married community members were carried out. Community health officers, community health volunteers, and health care managers were also interviewed using a semi-structured interview guide. FGDs and in-depth interviews were recorded digitally, transcribed verbatim, and analyzed using QSR Nvivo 10 to compare contraceptive misconceptions in northern and southern Ghana. Results indicate that misconceptions associated with the use of contraceptives were widespread but similar in both settings. Contraceptives were perceived to predispose women to both primary and secondary infertility, uterine fibroids, and cancers. As regular menstrual flow was believed to prevent uterine fibroids, contraceptive use-related amenorrhea was thought to render acceptors vulnerable to uterine fibroids as well as cervical and breast cancers. Contraceptive acceptors were stigmatized and ridiculed as promiscuous. Among northern respondents, condom use was generally perceived to inhibit erection and therefore capable of inducing male impotence, while in southern Ghana, condom use was believed to reduce sensation and sexual gratification. The study indicates that misconceptions associated with contraceptive use are widespread in both regions. Moreover, despite profound social and contextual differences that distinguish northern and southern Ghanaians, prevailing fears and misconceptions are shared by respondents from both settings. Findings attest to the need for improved communication to provide accurate information for dispelling these misconceptions.

"If you do vasectomy and come back here weak, I will divorce you": a qualitative study of community perceptions about vasectomy in Southern Ghana.

BACKGROUND: Male involvement in contraceptive use is increasingly becoming a global reproductive health issue. Vasectomy is one of the two male modern contraceptive methods espoused by the National Family Planning Policy in Ghana. Despite these advocacies, there are reports of low patronage of this method in Ghana. This study adhering to RATS guidelines on qualitative research therefore explored the social and cultural factors that may be affecting the low vasectomy uptake in Southern Ghana. METHODS: The study was conducted in Sefwi Bibiani-Ahwiaso Bekwai (SBAB) District and Komenda-Edina-Eguafo-Abrem (KEEA) Municipal area in the Western and Central regions of Ghana respectively. Twelve Focus Group Discussions were held with both male and female community members. In-depth interviews were also carried out with Community Health Officers (CHOs), Community Health Volunteers (CHVs) and health managers at both the district and regional levels. The discussions and interviews were recorded, transcribed verbatim and analysed using Nvivo 10. RESULTS: The study revealed that vasectomy was perceived as an act against God, which was punishable either by death or answerable on judgement day. Vasectomy was also perceived to be a form of castration, which can make men weak and incapable, thereby unable to satisfy their wives sexually, leading to marital conflicts. Women were more concerned about the negative effects of vasectomy on men. Cafalgin and panacin which are locally manufactured analgesics were perceived to have contraceptive abilities and therefore used by men as an alternative to modern contraceptive methods. CONCLUSIONS: Stigma and the misconceptions in the community may be accounting for the low vasectomy uptake in Ghana despite several advocacy strategies. Women were highly influential in a man's decision on vasectomy. This calls for the need to increase health education to demystify the misconceptions about vasectomy. Vasectomy-related campaign messages should target both men and women.

The Architecture of a Software System for Supporting Community-based Primary Health Care with Mobile Technology: The Mobile Technology for Community Health (MoTeCH) Initiative in Ghana.

THIS PAPER DESCRIBES THE SOFTWARE ARCHITECTURE OF A SYSTEM DESIGNED IN RESPONSE TO THE HEALTH DEVELOPMENT POTENTIAL OF TWO CONCOMITANT TRENDS IN POOR COUNTRIES: i) The rapid expansion of community health worker deployment, now estimated to involve over a million workers in Africa and Asia, and ii) the global proliferation of mobile technology coverage and use. Known as the Mobile Technology for Community Health (MoTeCH) Initiative, our system adapts and integrates existing software applications for mobile data collection, electronic medical records, and interactive voice response to bridge health information gaps in rural Africa. MoTeCH calculates the upcoming schedule of care for each client and, when care is due, notifies the client and community health workers responsible for that client. MoTeCH also automates the aggregation of health status and health service delivery information for routine reports. The paper concludes with a summary of lessons learned and future system development needs.

Hospitalized patients with 2009 pandemic influenza A (H1N1) virus infection in the United States--September-October 2009.

Given the potential worsening clinical severity of 2009 pandemic influenza A (H1N1) virus (pH1N1) infection from spring to fall 2009, we conducted a clinical case series among patients hospitalized with pH1N1 infection from September through October 2009. A case patient was defined as a hospitalized person who had test results positive for pH1N1 virus by real-time reverse-transcription polymerase chain reaction. Among 255 hospitalized patients, 34% were admitted to an intensive care unit and 8% died. Thirty-four percent of patients were children <18 years of age, 8% were adults ≥ 65 years of age, and 67% had an underlying medical condition. Chest radiographs obtained at hospital admission that had findings that were consistent with pneumonia were noted in 103 (46%) of 255 patients. Among 255 hospitalized patients, 208 (82%) received neuraminidase inhibitors, but only 47% had treatment started ≤ 2 days after illness onset. Overall, characteristics of hospitalized patients with pH1N1 infection in fall 2009 were similar to characteristics of patients hospitalized with pH1N1 infection in spring 2009, which suggests that clinical severity did not change substantially over this period.

A comparison of experience-dependent locomotory behaviors and biogenic amine neurons in nematode relatives of Caenorhabditis elegans.

BACKGROUND: Survival of an animal depends on its ability to match its responses to environmental conditions. To generate an optimal behavioral output, the nervous system must process sensory information and generate a directed motor output in response to stimuli. The nervous system should also store information about experiences to use in the future. The diverse group of free-living nematodes provides an excellent system to study macro- and microevolution of molecular, morphological and behavioral character states associated with such nervous system function. We asked whether an adaptive behavior would vary among bacterivorous nematodes and whether differences in the neurotransmitter systems known to regulate the behavior in one species would reflect differences seen in the adaptive behavior among those species. Caenorhabditis elegans worms slow in the presence of food; this 'basal' slowing is triggered by dopaminergic mechanosensory neurons that detect bacteria. Starved worms slow more dramatically; this 'enhanced' slowing is regulated by serotonin. RESULTS: We examined seven nematode species with known phylogenetic relationship to C. elegans for locomotory behaviors modulated by food (E. coli), and by the worm's recent history of feeding (being well-fed or starved). We found that locomotory behavior in some species was modulated by food and recent feeding experience in a manner similar to C. elegans, but not all the species tested exhibited these food-modulated behaviors. We also found that some worms had different responses to bacteria other than E. coli. Using histochemical and immunological staining, we found that dopaminergic neurons were very similar among all species. For instance, we saw likely homologs of four bilateral pairs of dopaminergic cephalic and deirid neurons known from C. elegans in all seven species examined. In contrast, there was greater variation in the patterns of serotonergic neurons. The presence of presumptive homologs of dopaminergic and serotonergic neurons in a given species did not correlate with the observed differences in locomotory behaviors. CONCLUSIONS: This study demonstrates that behaviors can differ significantly between species that appear morphologically very similar, and therefore it is important to consider factors, such as ecology of a species in the wild, when formulating hypotheses about the adaptive significance of a behavior. Our results suggest that evolutionary changes in locomotory behaviors are less likely to be caused by changes in neurotransmitter expression of neurons. Such changes could be caused either by subtle changes in neural circuitry or in the function of the signal transduction pathways mediating these behaviors.