Twenty-year follow-up of the facial phenotype of Brazilian patients with Sotos syndrome.

Sotos syndrome is characterized by overgrowth starting before birth through childhood with intellectual disability and craniofacial anomalies. The majority of patients are large for gestational age with developmental delay or intellectual disability. The majority of cases are caused by pathogenic variants in NSD1. The most consistent physical features in this disorder are facial dysmorphisms including prominent forehead, downslanted palpebral fissures, prognathism with a pointed chin, and a long and narrow face. We present a follow-up to a cohort of 11 individuals found to harbor heterozygous, pathogenic, or likely pathogenic variants in NSD1. We analyzed the facial dysmorphisms and the condition using retrospective over 20 years. Among these patients, followed in our medical genetics outpatient clinic for variable periods of time, all had a phenotype compatible with the characteristic Sotos syndrome facial features, which evolved with time and became superimposed with natural aging modifications. We present here a long-term follow-up of facial features of Brazilian patients with molecularly confirmed Sotos syndrome. In this largest Brazilian cohort of molecularly confirmed patients with Sotos syndrome to date, we provide a careful description of the facial phenotype, which becomes less pronounced with aging and possibly more difficult to recognize in adults. These results may have broad clinical implications for diagnosis and add to the global clinical delineation of this condition.

Impact of Exercise Modalities on Peripheral and Central Components of Cardiorespiratory Capacity in Heart Transplantation Patients: A Systematic Review and Meta-Analysis.

Background and Objectives: To analyze the effects of aerobic, resistance, and combined training on peripheral and central components related to cardiorespiratory capacity after HTx. Materials and Methods: No time restriction was applied for study inclusion. MEDLINE/PubMed; EMBASE, CENTRAL, and PEDro databases were investigated. Studies reporting heart transplanted patients older than 19 years following aerobic, resistance, and combined training according. The outcomes included: V'O2 peak, VE/V'CO2 slope, heart rate (HR peak), systolic and diastolic blood pressure (SBP and DBP peak), maximum repetition test(1RM), sit-to-stand test, and flow-mediated dilation (FMD). The studies were selected by consensus. Four hundred ninety-two studies initially met the selection criteria. Cochrane handbook was used for abstracting data and assessing data quality and validity. Independent extraction by two observers was applied. Results: Isolated aerobic training leads to a greater increase in V'O2 peak than combined training compared to the control group (p < 0.001, I2 = 0%). However, no significant differences were found in the subgroup comparison (p = 0.19, I2 = 42.1%). HR peak increased similarly after aerobic and combined training. High-intensity interval training (HIIT) was better than moderate continuous intensity to increase the V'O2 after long term in HTx. Still, there is scarce evidence of HIIT on muscle strength and FMD. No change on VE/V'CO2 slope, FMD, and SBP, DBP peak. 1RM and the sit-to-stand test increased after resistance training (p < 0.001, I2 = 70%) and CT (p < 0.001, I2 = 0%) when compared to control. Conclusions: Aerobic and combined training effectively improve VO2 peak and muscle strength, respectively. HIIT seems the better choice for cardiorespiratory capacity improvements. More studies are needed to examine the impact of training modalities on VE/V'CO2 slope and FMD.

In Vitro Induction of Pluripotency from Equine Fibroblasts in 20% or 5% Oxygen.

The cellular reprogramming into pluripotency is influenced by external and internal cellular factors, such as in vitro culture conditions (e.g., environmental oxygen concentration), and the aging process. Herein, we aimed to generate and maintain equine iPSCs (eiPSCs) derived from fibroblasts of a horse older than 20 years and to evaluate the effect of different levels of oxygen tension (atmospheric 20% O2, 5% O2, or 20% to 5% O2) on these cells. Fibroblasts were reprogrammed, and putative eiPSCs were positive for positive alkaline phosphatase detection; they were positive for pluripotency-related genes OCT4, REX1, and NANOG; immunofluorescence-positive staining was presented for OCT4 and NANOG (all groups), SOX2 (groups 5% O2 and 20% to 5% O2), and TRA-1-60, TRA-1-81, and SSEA-1 (only in 20% O2); they formed embryoid bodies; and there is spontaneous differentiation in mesoderm, endoderm, and ectoderm embryonic germ layers. In addition to the differences in immunofluorescence analysis results, the eiPSC colonies generated at 20% O2 presented a more compact morphology with a well-defined border than cells cultured in 5% O2 and 20% to 5% O2. Significant differences were also observed in the expression of genes related to glucose metabolism, mitochondrial fission, and hypoxia (GAPDH, GLUT3, MFN1, HIF1α, and HIF2α), after reprogramming. Our results show that the derivation of eiPSCs was not impaired by aging. Additionally, this study is the first to compare high and low oxygen cultures of eiPSCs, showing the generation of pluripotent cells with different profiles. Under the tested conditions, the lower oxygen tension did not favor the pluripotency of eiPSCs. This study shows that the impact of oxygen atmosphere has to be considered when culturing eiPSCs, as this condition influences the pluripotency characteristics.

Testosterone Recovery Profiles After Cessation of Androgen Deprivation Therapy for Prostate Cancer.

INTRODUCTION: Androgen deprivation therapy (ADT) is frequently used in the treatment of prostate cancer worldwide. Variable testosterone (T) recovery profiles after ADT cessation have been cited. AIM: To evaluate T recovery after cessation of ADT. METHODS: We reviewed our institutional prospectively maintained database of patients with prostate cancer who received ADT. Serum early morning total T (TT) levels, collected at baseline and periodically after ADT cessation, were analyzed. Patient age, baseline T level, duration of ADT, and presence of diabetes and sleep apnea were selected as potential predictors of T recovery. 3 metrics of T recovery after 24 months of ADT cessation were analyzed: return to non-castrate level (TT > 50 ng/dL), return to normal (T > 300 ng/dL), and return back to baseline level (BTB). Multivariable time-to-event analysis (Cox proportional hazards), χ2 test, logistic regression model, and Kaplan-Meier curve were performed to define impact of the above predictors on time and chance of T recovery. MAIN OUTCOME MEASURES: Time and chance of T recovery to non-castrate level (TT > 50 ng/dL), return to normal (T > 300 ng/dL), and return BTB. RESULTS: 307 men with a mean age of 65 ± 8 years were included. Mean duration of ADT was 17 ± 25 months, and median follow-up was 31 ± 35 months. Mean TT values were 379 ng/dL at baseline and 321 ng/dL at >24 months. At 24 months after cessation of ADT, 8% of men remained at castrate level, 76% returned to TT >300 ng/dL, and 51% had returned BTB. Lower baseline T levels (TT < 400 ng/dL) and ADT duration >6 months were associated with a lower likelihood of recovery to normal TT at 24 months. Age >65 years and receiving ADT for >6 months were significantly associated with a slower T recovery. CLINICAL IMPLICATIONS: T recovery after ADT is not certain and may take longer than expected. Considering the range of side effects of low T, we believe that these findings must be discussed with patients before initiating such therapies. STRENGTHS & LIMITATIONS: Our strengths consisted of a relatively large database, long follow-up, and clinically meaningful endpoints. Limitations included the retrospective design of the study. CONCLUSION: T recovery rates after ADT cessation vary according to patient age, ADT duration, and baseline T levels. Approximately one-quarter of patients failed to normalize their TT level, and one-tenth of men remained at castrate levels 24 months after ADT cessation. Nascimento B, Miranda EP, Jenkins LC, et al. Testosterone Recovery Profiles After Cessation of Androgen Deprivation Therapy for Prostate Cancer. J Sex Med 2019;16:872-879.

Development, Validation, and Dissemination of a Breast Cancer Recurrence Detection and Timing Informatics Algorithm.

Background: This study developed, validated, and disseminated a generalizable informatics algorithm for detecting breast cancer recurrence and timing using a gold standard measure of recurrence coupled with data derived from a readily available common data model that pools health insurance claims and electronic health records data. Methods: The algorithm has two parts: to detect the presence of recurrence and to estimate the timing of recurrence. The primary data source was the Cancer Research Network Virtual Data Warehouse (VDW). Sixteen potential indicators of recurrence were considered for model development. The final recurrence detection and timing models were determined, respectively, by maximizing the area under the ROC curve (AUROC) and minimizing average absolute error. Detection and timing algorithms were validated using VDW data in comparison with a gold standard recurrence capture from a third site in which recurrences were validated through chart review. Performance of this algorithm, stratified by stage at diagnosis, was compared with other published algorithms. All statistical tests were two-sided. Results: Detection model AUROCs were 0.939 (95% confidence interval [CI] = 0.917 to 0.955) in the training data set (n = 3370) and 0.956 (95% CI = 0.944 to 0.971) and 0.900 (95% CI = 0.872 to 0.928), respectively, in the two validation data sets (n = 3370 and 3961, respectively). Timing models yielded average absolute prediction errors of 12.6% (95% CI = 10.5% to 14.5%) in the training data and 11.7% (95% CI = 9.9% to 13.5%) and 10.8% (95% CI = 9.6% to 12.2%) in the validation data sets, respectively, and were statistically significantly lower by 12.6% (95% CI = 8.8% to 16.5%, P < .001) than those estimated using previously reported timing algorithms. Similar covariates were included in both detection and timing algorithms but differed substantially from previous studies. Conclusions: Valid and reliable detection of recurrence using data derived from electronic medical records and insurance claims is feasible. These tools will enable extensive, novel research on quality, effectiveness, and outcomes for breast cancer patients and those who develop recurrence.

Small Ca2+ releases enable hour-long high-frequency contractions in midshipman swimbladder muscle.

Type I males of the Pacific midshipman fish (Porichthys notatus) vibrate their swimbladder to generate mating calls, or "hums," that attract females to their nests. In contrast to the intermittent calls produced by male Atlantic toadfish (Opsanus tau), which occur with a duty cycle (calling time divided by total time) of only 3-8%, midshipman can call continuously for up to an hour. With 100% duty cycles and frequencies of 50-100 Hz (15°C), the superfast muscle fibers that surround the midshipman swimbladder may contract and relax as many as 360,000 times in 1 h. The energy for this activity is supported by a large volume of densely packed mitochondria that are found in the peripheral and central regions of the fiber. The remaining fiber cross section contains contractile filaments and a well-developed network of sarcoplasmic reticulum (SR) and triadic junctions. Here, to understand quantitatively how Ca2+ is managed by midshipman fibers during calling, we measure (a) the Ca2+ pumping-versus-pCa and force-versus-pCa relations in skinned fiber bundles and (b) changes in myoplasmic free [Ca2+] (Δ[Ca2+]) during stimulated activity of individual fibers microinjected with the Ca2+ indicators Mag-fluo-4 and Fluo-4. As in toadfish, the force-pCa relation in midshipman is strongly right-shifted relative to the Ca2+ pumping-pCa relation, and contractile activity is controlled in a synchronous, not asynchronous, fashion during electrical stimulation. SR Ca2+ release per action potential is, however, approximately eightfold smaller in midshipman than in toadfish. Midshipman fibers have a larger time-averaged free [Ca2+] during activity than toadfish fibers, which permits faster Ca2+ pumping because the Ca2+ pumps work closer to their maximum rate. Even with midshipman's sustained release and pumping of Ca2+, however, the Ca2+ energy cost of calling (per kilogram wet weight) is less than twofold more in midshipman than in toadfish.

Using Maslow's hierarchy to highlight power imbalances between visiting health professional student volunteers and the host community: An applied qualitative study.

BACKGROUND: Health professional students from high-income countries increasingly participate in short-term experiences in global health (STEGH) conducted abroad. One common criticism of STEGH is the inherent power differential that exists between visiting learners and the local community. To highlight this power differential, this paper explores perceived benefits as described by volunteer and community respondents and applies Maslow's hierarchy of needs to commonly identified themes in each respondent group. METHODS: A semistructured survey was used to collect qualitative responses from both volunteers and community members located in a Dominican Republic community, that is, a hotspot for traditionally conducted STEGH. Thematic analysis identified themes of perceived benefits from both respondent groups; each group's common themes were then classified and compared within Maslow's hierarchy of needs. RESULTS: Each respondent group identified resource provision as a perceived benefit of STEGH, but volunteer respondents primarily focused on the provision of highly-skilled, complex resources while community respondents focused on basic necessities (food, water, etc.) Volunteer respondents were also the only group to also mention spiritual/religious/life experiences, personal skills development, and relationships as perceived benefits. Applying Maslow's hierarchy thus demonstrates a difference in needs: community respondents focused on benefits that address deficiency needs at the bottom of the hierarchy while volunteers focused on benefits addressing self-transcendence/actualization needs at the top of the hierarchy. CONCLUSIONS: The perceived difference in needs met by STEGH between volunteers and the host community within Maslow's hierarchy may drive an inherent power differential. Refocusing STEGH on the relationship level of the hierarchy (i.e., focusing on partnerships) might help mitigate this imbalance and empower host communities.

Central Nervous System and Vertebrae Development in Horses: a Chronological Study with Differential Temporal Expression of Nestin and GFAP.

The neural system is one of the earliest systems to develop and the last to be fully developed after birth. This study presents a detailed description of organogenesis of the central nervous system (CNS) at equine embryonic/fetal development between 19 and 115 days of pregnancy. The expression of two important biomarkers in the main structure of the nervous system responsible for neurogenesis in the adult individual, and in the choroid plexus, was demonstrated by Nestin and glial fibrillary acid protein (GFAP) co-labeling. In the 29th day of pregnancy in the undifferentiated lateral ventricle wall, the presence of many cells expressing Nestin and few expressing GFAP was observed. After the differentiation of the lateral ventricle wall zones at 60 days of pregnancy, the subventricular zone, which initially had greater number of Nestin+ cells, began to show higher numbers of GFAP+ cells at 90 days of pregnancy. A similar pattern was observed for Nestin+ and GFAP+ cells during development of the choroid plexus. This study demonstrates, for the first time, detailed chronological aspects of the equine central nervous system organogenesis associated with downregulation of Nestin and upregulation of GFAP expression.

Steric Clash in the SET Domain of Histone Methyltransferase NSD1 as a Cause of Sotos Syndrome and Its Genetic Heterogeneity in a Brazilian Cohort.

Most histone methyltransferases (HMTase) harbor a predicted Su(var)3-9, Enhancer-of-zeste, Trithorax (SET) domain, which transfers a methyl group to a lysine residue in their substrates. Mutations of the SET domains were reported to cause intellectual disability syndromes such as Sotos, Weaver, or Kabuki syndromes. Sotos syndrome is an overgrowth syndrome with intellectual disability caused by haploinsufficiency of the nuclear receptor binding SET domain protein 1 (NSD1) gene, an HMTase at 5q35.2-35.3. Here, we analyzed NSD1 in 34 Brazilian Sotos patients and identified three novel and eight known mutations. Using protein modeling and bioinformatic approaches, we evaluated the effects of one novel (I2007F) and 21 previously reported missense mutations in the SET domain. For the I2007F mutation, we observed conformational change and loss of structural stability in Molecular Dynamics (MD) simulations which may lead to loss-of-function of the SET domain. For six mutations near the ligand-binding site we observed in simulations steric clashes with neighboring side chains near the substrate S-Adenosyl methionine (SAM) binding site, which may disrupt the enzymatic activity of NSD1. These results point to a structural mechanism underlying the pathology of the NSD1 missense mutations in the SET domain in Sotos syndrome. NSD1 mutations were identified in only 32% of the Brazilian Sotos patients in our study cohort suggesting other genes (including unknown disease genes) underlie the molecular etiology for the majority of these patients. Our studies also found NSD1 expression to be profound in human fetal brain and cerebellum, accounting for prenatal onset and hypoplasia of cerebellar vermis seen in Sotos syndrome.

Health and Social Needs in Three Migrant Worker Communities around La Romana, Dominican Republic, and the Role of Volunteers: A Thematic Analysis and Evaluation.

Objective. For decades, Haitian migrant workers living in bateyes around La Romana, Dominican Republic, have been the focus of short-term volunteer medical groups from North America. To assist these efforts, this study aimed to characterize various health and social needs that could be addressed by volunteer groups. Design. Needs were assessed using semistructured interviews of community and professional informants, using a questionnaire based on a social determinants of health framework, and responses were qualitatively analysed for common themes. Results. Key themes in community responses included significant access limitations to basic necessities and healthcare, including limited access to regular electricity and potable water, lack of health insurance, high out-of-pocket costs, and discrimination. Healthcare providers identified the expansion of a community health promoter program and mobile medical teams as potential solutions. English and French language training, health promotion, and medical skills development were identified as additional strategies by which teams could support community development. Conclusion. Visiting volunteer groups could work in partnership with community organizations to address these barriers by providing short-term access to services, while developing local capacity in education, healthcare, and health promotion in the long-term. Future work should also carefully evaluate the impacts and contributions of such volunteer efforts.

Coalicion de Salud Comunitaria (COSACO): using a Healthy Community Partnership framework to integrate short-term global health experiences into broader community development.

BACKGROUND: There is growing concern that short-term experiences in global health experiences (STEGH), undertaken by healthcare providers, trainees, and volunteers from high income countries in lower and middle income countries, risk harming the community by creating a parallel system of care separate from established community development efforts. At the same time, the inclusion of non-traditional actors in health planning has been the basis of the development of many Healthy Community Partnerships (HCP) being rolled out in Canada and the United States. These partnerships aim to bring all stakeholders with a role to play in health to the table to align efforts, goals and programs towards broad community health goals. RESULTS: This methodology paper reports on the process used in La Romana, Dominican Republic, in applying a modified HCP framework. This project succeeded at bringing visiting STEGH organizations into a coalition with key community partners and supported attempts to embed the work of STEGH within longer-term, established development plans. CONCLUSIONS: In presenting the work and process and lessons learned, the hope is that other communities that encounter significant investment from STEGH groups, and will gain the same benefits that were seen in La Romana with regards to improved information exchange, increased cross-communication between silos, and the integration of STEGH into the work of community partners.

Nicotinamide mononucleotide supplementation reverses vascular dysfunction and oxidative stress with aging in mice.

We tested the hypothesis that supplementation of nicotinamide mononucleotide (NMN), a key NAD(+) intermediate, increases arterial SIRT1 activity and reverses age-associated arterial dysfunction and oxidative stress. Old control mice (OC) had impaired carotid artery endothelium-dependent dilation (EDD) (60 ± 5% vs. 84 ± 2%), a measure of endothelial function, and nitric oxide (NO)-mediated EDD (37 ± 4% vs. 66 ± 6%), compared with young mice (YC). This age-associated impairment in EDD was restored in OC by the superoxide (O2-) scavenger TEMPOL (82 ± 7%). OC also had increased aortic pulse wave velocity (aPWV, 464 ± 31 cm s(-1) vs. 337 ± 3 cm s(-1) ) and elastic modulus (EM, 6407 ± 876 kPa vs. 3119 ± 471 kPa), measures of large elastic artery stiffness, compared with YC. OC had greater aortic O2- production (2.0 ± 0.1 vs. 1.0 ± 0.1 AU), nitrotyrosine abundance (a marker of oxidative stress), and collagen-I, and reduced elastin and vascular SIRT1 activity, measured by the acetylation status of the p65 subunit of NFκB, compared with YC. Supplementation with NMN in old mice restored EDD (86 ± 2%) and NO-mediated EDD (61 ± 5%), reduced aPWV (359 ± 14 cm s(-1) ) and EM (3694 ± 315 kPa), normalized O2- production (0.9 ± 0.1 AU), decreased nitrotyrosine, reversed collagen-I, increased elastin, and restored vascular SIRT1 activity. Acute NMN incubation in isolated aortas increased NAD(+) threefold and manganese superoxide dismutase (MnSOD) by 50%. NMN supplementation may represent a novel therapy to restore SIRT1 activity and reverse age-related arterial dysfunction by decreasing oxidative stress.

Short-term global health education programs abroad: disease patterns observed in Haitian migrant worker communities around La Romana, Dominican Republic.

The possibility of encountering rare tropical disease presentations is commonly described as a benefit derived by developed world medical trainees participating in clinical service-oriented short-term global health experiences in the developing world. This study describes the health status of a population served by a short-term experience conducted by a North American institute, and the results of a retrospective review are used to identify commonly encountered diseases and discuss their potential educational value. Descriptive analysis was conducted on 1,024 encounter records collected over four unique 1-week-long trips by a North American institution serving Haitian migrant workers in La Romana, Dominican Republic. The top five diagnoses seen in the clinic were gastroesophageal reflux disease (GERD), hypertension (HTN), upper respiratory infections, otitis media, and fungal skin infection. On occasion, diagnoses unique to an indigent tropical population were encountered (e.g., dehydration, malnutrition, parasites, and infections.). These findings suggest a similarity between frequently encountered diagnoses on a short-term clinical service trip in Dominican Republic and primary care presentations in developed world settings, which challenges the assumption that short-term service experiences provide exposure to rare tropical disease presentations. These findings also represent additional data that can be used to better understand the health and healthcare planning among this vulnerable population of Haitian migrant workers.

Political power and health inequalities in Vieques, Puerto Rico.

The relationship between political power and the various pathways to health inequalities in Vieques, Puerto Rico, is explored. The U.S. Navy used the island for 62 years for bombing and other military exercises. The article focuses on the resulting changes to the island's socioeconomic positioning and the health inequalities over six decades. Secondary data analysis of census data using a revised World Health Organization model is used to examine the relationships of political power, labor markets, employment, material deprivation, social and family networks, and health inequalities. Findings are interpreted through a social justice lens and implications suggest the use of political advocacy for social change.

Private sector contributions and their effect on physician emigration in the developing world.

The contribution made by the private sector to health care in a low- or middle-income country may affect levels of physician emigration from that country. The increasing importance of the private sector in health care in the developing world has resulted in newfound academic interest in that sector's influences on many aspects of national health systems. The growth in physician emigration from the developing world has led to several attempts to identify both the factors that cause physicians to emigrate and the effects of physician emigration on primary care and population health in the countries that the physicians leave. When the relevant data on the emerging economies of Ghana, India and Peru were investigated, it appeared that the proportion of physicians participating in private health-care delivery, the percentage of health-care costs financed publicly and the amount of private health-care financing per capita were each inversely related to the level of physician expatriation. It therefore appears that private health-care delivery and financing may decrease physician emigration. There is clearly a need for similar research in other low- and middle-income countries, and for studies to see if, at the country level, temporal trends in the contribution made to health care by the private sector can be related to the corresponding trends in physician emigration. The ways in which private health care may be associated with access problems for the poor and therefore reduced equity also merit further investigation. The results should be of interest to policy-makers who aim to improve health systems worldwide.

La contribution apportée par le secteur privé aux soins de santé dans les pays à revenu faible ou intermédiaire peut modifier les taux d'émigration des médecins de ces pays. L'importance croissante du secteur privé dans les soins de santé dans les pays en voie de développement a suscité un regain d'intérêt académique dans les influences de ce secteur sur de nombreux aspects des systèmes de santé nationaux. La croissance de l'émigration des médecins des pays en voie de développement a conduit à plusieurs tentatives d'identifier à la fois les facteurs qui incitent les médecins à émigrer et les effets de l'émigration des médecins sur les soins primaires et la santé de la population dans les pays qu'ils quittent. Lorsque les données pertinentes sur les économies émergentes du Ghana, de l'Inde et du Pérou ont été étudiées, il est apparu que la proportion de médecins qui participent à la prestation des soins privés, le pourcentage de dépenses de santé financées publiquement et le montant du financement des soins de santé privés par habitant ont été chacun inversement proportionnels au taux d'expatriation des médecins. Ainsi, la prestation et le financement de soins de santé privés peuvent réduire l'émigration des médecins. Il existe clairement un besoin de recherches similaires dans d'autres pays à revenus faible et intermédiaire, ainsi que d'études pour voir si, au niveau du pays, les tendances temporelles de la contribution aux soins de santé par le secteur privé peuvent être liées aux tendances correspondantes de l'émigration des médecins. Les façons dont les soins de santé privés peuvent être associés à des problèmes d'accès pour les pauvres et, par conséquent l'équité réduite, méritent également une enquête plus approfondie. Les résultats devraient intéresser les décideurs politiques qui visent à améliorer les systèmes de santé à travers le monde.

La aportación del sector privado a la atención sanitaria en un país de ingresos medios o bajos puede repercutir en los índices de emigración de médicos de dicho país. La importancia creciente del sector privado en la atención sanitaria en los países en desarrollo ha suscitado un nuevo interés entre los académicos respecto a las influencias de dicho sector sobre muchos aspectos de los sistemas sanitarios nacionales. El aumento de la emigración de médicos procedentes de países en desarrollo ha conducido a varios intentos de identificar, por un lado, los factores implicados en la emigración de médicos y, por otro lado, los efectos de la emigración de médicos sobre la atención primaria y la salud de la población de los países de donde parten los médicos. Tras investigar la información pertinente sobre las economías emergentes de Ghana, India y Perú, se halló una relación inversa entre el índice de médicos expatriados y cada uno de los siguientes factores: la proporción de médicos que prestan atención sanitaria dentro del sector sanitario privado, el porcentaje de los costes sanitarios financiados con fondos públicos y la cuantía de la financiación per cápita del sector sanitario privado. Por consiguiente, parece ser que la prestación de servicios sanitarios por parte del sector privado y la financiación pueden reducir la emigración de médicos. Resulta evidente la necesidad de realizar investigaciones similares en otros países de renta media y baja, así como estudios que esclarezcan si, a escala nacional, se pueden vincular las tendencias temporales de la contribución por parte del sector privado con las correspondientes tendencias de la emigración de médicos. Cómo la sanidad privada puede relacionarse con los problemas de acceso para los pobres y, por lo tanto, con la reducción de la equidad, merece asimismo mayor investigación. Los resultados podrían ser de interés para los responsables políticos que aspiren a mejorar los sistemas sanitarios a escala mundial.

Common genetic variants in the endothelial system predict blood pressure response to sodium intake: the GenSalt study.

BACKGROUND We examined the association between 14 endothelial system genes and salt-sensitivity of blood pressure (BP). METHODS After a 3-day baseline examination, during which time the usual diet was consumed, 1,906 Chinese participants received a 7-day low-sodium diet (51.3 mmol of sodium/day) followed by a 7-day high-sodium diet (307.8 mmol of sodium/day). BP measurements were obtained at baseline and at the end of each intervention using a random-zero sphygmomanometer. RESULTS The DDAH1 rs11161637 variant was associated with reduced BP salt sensitivity, conferring attenuated systolic BP (SBP) and mean arterial pressure (MAP) decreases from baseline to the low-sodium intervention (both P = 2×10(-4)). Examination of genotype-sex interactions revealed that this relation was driven by the strong associations observed in men (P for interactions = 1.10×10(-4) and 0.008, respectively). When switching from the low- to high-sodium intervention, increases in diastolic BP (DBP) and MAP were attenuated by the COL18A1 rs2838944 minor A allele (P = 1.41×10(-4) and 1.55×10(-4), respectively). Conversely, the VWF rs2239153 C variant was associated with increased salt sensitivity, conferring larger DBP and MAP reductions during low-sodium intervention (P = 1.22×10(-4) and 4.44×10(-5), respectively). Ten variants from 3 independent SELE loci displayed significant genotype-sex interactions on DBP and MAP responses to low-sodium (P for interaction = 1.56×10(-3) to 1.00×10(-4)). Among men, minor alleles of 4 correlated markers attenuated BP responses to low-sodium intake, whereas minor alleles of another 4 correlated markers increased BP responses. No associations were observed in women for these variants. Further, qualitative interactions were shown for 2 correlated SELE markers. CONCLUSIONS These data support a role for the endothelial system genes in salt sensitivity.

Educator perceptions of the relationship between education innovations and improved health.

BACKGROUND: Education innovations by health professions faculty are shaped by faculty conceptualizations of the pathway between their innovations and changes in health of communities. AIMS: We aimed to explore how existing theories about the relationship between education and health are attended to, interpreted, and applied by faculty in different national contexts. METHODS: We compared existing theoretical frameworks to perceptions of "front line" faculty. Fellows in Brazil- and India-based FAIMER faculty development programs were asked via questionnaires about the contribution of their education innovation projects to health improvements. RESULTS: Faculty identified pathways to improved societal health via increased quality, and to a lesser extent relevance, of education. Relationships between increased quantity of education and improved health were focused on faculty development. Faculty from both countries noted the value for health outcomes of innovations that affect networks and partnerships with other institutions. Faculty from India identified pathways to improved societal health via changes to instructional more than institutional processes. CONCLUSIONS: Results indicate where there are gaps in existing theories, a need to raise awareness about potential pathways to improving health via education changes, and opportunities for more detailed understanding of mechanisms of change via in-depth research.