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Background: Lysine is one of the essential amino acids and in cereal based diets it is known to be the most limiting and therefore determines the quality of dietary protein in such diets. This study investigated the effect of lysine supplementation on blood pressure of hypertensive adults in selected peri-urban community in Accra, Ghana., Methods: The study was a randomized double-blind controlled study made up of adults men and women assigned to a lysine supplemented group and a placebo-supplemented (control) group. The subjects aged between 18 - 45 years and totaling 180., Results: Total of 50 (28%) of the participating were hypertensive defined as Systolic Blood Pressure (SBP) ≥140 mmHg. The mean SBP of lysine-supplemented group significantly dropped from 146.11 ± 11.92 to 128.95 ± 10.44 mmHg ( p  = 0.02). That of women also dropped from 144.12 ± 10.41 to 132.28 ± 10.69 mmHg, ( p  = 0.06 while the control group had there SBP remained fairly constant after 112 days of intervention with changes in men from 145.79 ± 12.56 to 142.79 ± 11.07 mmHg ( p  = 0.32) and women in the control had very little drop from 145.15 ± 14.79 to 145.00 ± 17.93 mmHg ( p  = 0.96)., Conclusion: Lysine supplementation resulted in normalization/reduction of blood pressure of hypertensive subjects who have suboptimal lysine intake., Competing Interests: Competing interestsThe authors declare that they have no competing interest., (© The Author(s). 2017.)

Background: In psychosis, white matter (WM) microstructural changes have been detected previously; however, direct comparisons of findings between bipolar (BD) and schizophrenia (SZ) patients are scarce. In this study, we employed deterministic tractography to reconstruct WM tracts in BD and SZ patients., Methods: Diffusion tensor imaging (DTI) data was carried out with n=32 euthymic BD type I patients, n=26 SZ patients and 30 matched healthy controls. Deterministic tractography using multiple indices of diffusion (fractional anisotropy (FA), tract volume (Vol), tract length (Le) and number of tracts (NofT)) were obtained from the fornix, the cingulum, the anterior thalamic radiation, and the corpus callosum bilaterally., Results: We showed widespread WM microstructural changes in SZ, and changes in the corpus callosum, the left cingulum and the fornix in BD. Fornix fiber tracking scores were associated with cognitive performance in SZ, and with age and age at disease onset in the BD patient group., Limitations: Although the influence of psychopharmacological drugs as biasing variables on morphological alterations has been discussed for SZ and BD, we did not observe a clear influence of drug exposure on our findings., Conclusions: These results confirm the assumption that SZ patients have more severe WM changes than BD patients. The findings also suggest a major role of WM changes in the fornix as important fronto-limbic connections in the etiology of cognitive symptoms in SZ, but not in BD., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Cognitive impairments have been linked to structural and functional alterations in frontal and subcortical brain regions, ultimately leading to fronto-thalamic connectivity disturbances. We hypothesized that such neuronal disruptions in frontal and subcortical structures may account for neuropsychological deficits in schizophrenia (SZ), schizophrenia relatives and bipolar disorder (BD). We acquired T1-weighted anatomical MRI sequences in 209 participants: 57 SZ patients, 47 first-degree relatives of SZ patients, 48 BD I patients and 57 healthy controls. We computed group comparisons of gray matter (GM) volume in frontal and basal ganglia regions-of-interest, followed by correlation analysis between psychomotor speed, executive functioning and learning and GM volumes in candidate regions. Several frontal GM volume reductions as well as GM increases in the thalamus and the putamen were exhibited in SZ patients as compared to controls. The same finding was observed - less pronounced - when comparing SZ relatives and controls. BD patients presented GM volume increases in the basal ganglia in comparison to controls. In SZ patients, increases in bilateral thalamus GM volume and decreases in left middle and superior frontal gyrus volume were significantly associated with worse cognitive performance. In summary, our results indicate distinct imbalances across frontal-subcortical circuits in BD, SZ relatives and SZ. The functional relevance of the findings were mainly limited to the SZ patients group: in this group, abnormalities were directly associated with cognitive performance. This result is in line with the finding that the volume alterations were strongest in SZ patients and followed by BD patients and SZ relatives., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Elevated levels of interleukin-18 (IL-18) are found in many chronic inflammatory disorders, including inflammatory bowel disease (IBD), and polymorphisms in the IL18R1-IL18RAP locus are associated with IBD susceptibility. IL-18 is an IL-1 family cytokine that has been proposed to promote barrier function in the intestine, but the effects of IL-18 on intestinal CD4(+) T cells are poorly understood. Here we demonstrate that IL-18R1 expression is enhanced on both effector and regulatory CD4(+) T cells in the intestinal lamina propria, with T helper type 17 (Th17) cells exhibiting particularly high levels. We further show that, during steady state, intestinal epithelial cells constitutively secrete IL-18 that acts directly on IL-18R1-expressing CD4(+) T cells to limit colonic Th17 cell differentiation, in part by antagonizing IL-1R1 signaling. In addition, although IL-18R1 is not required for colonic Foxp3(+) regulatory T (Treg) cell differentiation, we found that IL-18R1 signaling was critical for Foxp3(+) Treg cell-mediated control of intestinal inflammation, where it promoted the expression of key Treg effector molecules. Thus IL-18 is a key epithelial-derived cytokine that differentially regulates distinct subsets of intestinal CD4(+) T cells during both homeostatic and inflammatory conditions, a finding with potential implications for treatment of chronic inflammatory disorders.

Background: The global burden of disease is increasingly dominated by non-communicable diseases.These diseases are less amenable to curative and preventative interventions than communicable disease. This presents a challenge to medical practice and medical research, both of which are experiencing diminishing returns from increasing investment., Objective: Our aim was to (1) review how medical knowledge is generated, and its limitations, (2) assess the potential for emerging technologies and ideas to improve medical research, and (3) suggest solutions and recommendations to increase medical research efficiency on non-communicable diseases., Methods: We undertook an unsystematic review of peer-reviewed literature and technology websites., Results: Our review generated the following conclusions and recommendations. (1) Medical knowledge continues to be generated in a reductionist paradigm. This oversimplifies our models of disease, rendering them ineffective to sufficiently understand the complex nature of non-communicable diseases. (2) Some of these failings may be overcome by adopting a "Systems Medicine" paradigm, where the human body is modeled as a complex adaptive system. That is, a system with multiple components and levels interacting in complex ways, wherein disease emerges from slow changes to the system set-up. Pursuing systems medicine research will require larger datasets. (3) Increased data sharing between researchers, patients, and clinicians could provide this unmet need for data. The recent emergence of electronic health care records (EHR) could potentially facilitate this in real-time and at a global level. (4) Efforts should continue to aggregate anonymous EHR data into large interoperable data silos and release this to researchers. However, international collaboration, data linkage, and obtaining additional information from patients will remain challenging. (5) Efforts should also continue towards "Medicine 2.0". Patients should be given access to their personal EHR data. Subsequently, online communities can give researchers the opportunity to ask patients for direct access to the patient's EHR data and request additional study-specific information. However, selection bias towards patients who use Web 2.0 technology may be difficult to overcome., Conclusions: Systems medicine, when combined with large-scale data sharing, has the potential to raise our understanding of non-communicable diseases, foster personalized medicine, and make substantial progress towards halting, curing, and preventing non-communicable diseases. Large-scale data amalgamation remains a core challenge and needs to be supported. A synthesis of "Medicine 2.0" and "Systems Science" concepts into "Systems Medicine 2.0" could take decades to materialize but holds much promise.

NOD2 is an intracellular sensor that contributes to immune defense and inflammation. Here we investigated whether NOD2 mediates its effects through control of microRNAs (miRNAs). miR-29 expression was upregulated in human dendritic cells (DCs) in response to NOD2 signals, and miR-29 regulated the expression of multiple immune mediators. In particular, miR-29 downregulated interleukin-23 (IL-23) by targeting IL-12p40 directly and IL-23p19 indirectly, likely via reduction of ATF2. DSS-induced colitis was worse in miR-29-deficient mice and was associated with elevated IL-23 and T helper 17 signature cytokines in the intestinal mucosa. Crohn's disease (CD) patient DCs expressing NOD2 polymorphisms failed to induce miR-29 upon pattern recognition receptor stimulation and showed enhanced release of IL-12p40 on exposure to adherent invasive E. coli. Therefore, we suggest that loss of miR-29-mediated immunoregulation in CD DCs might contribute to elevated IL-23 in this disease., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Patients with inflammatory bowel disease (IBD) have an increased risk of colon cancer. However, the immune cells and cytokines that mediate the transition from intestinal inflammation to cancer are poorly understood. We show that bacteria-induced colon cancer is accompanied by differential accumulation of IL-17(+)IL-22(+) colonic innate lymphoid cells (cILCs), which are phenotypically distinct from LTi and NK-22 cells, and that their depletion in mice with dysplastic inflammation blocks the development of invasive colon cancer. Analysis of the functional role of distinct Type 17 cytokines shows that although blockade of IL-17 inhibits some parameters of intestinal inflammation, reduction in dysplasia and colorectal cancer (CRC) requires neutralization of IL-22 indicating a unique role for IL-22 in the maintenance of cancer in this model. Mechanistic analyses showed that IL-22 selectively acts on epithelial cells to induce Stat3 phosphorylation and proliferation. Importantly, we could detect IL-22(+)CD3(+) and IL-22(+)CD3(−) cells in human CRC. Our results describe a new activity of IL-22 in the colon as a nonredundant mediator of the inflammatory cascade required for perpetuation of CRC, highlighting the IL-22 axis as a novel therapeutic target in colon cancer.

Objectives: We sought to determine cardiovascular risk factor prevalence rates among adults in Abu Dhabi, United Arab Emirates., Methods: We used self-reported indicators, anthropometric measures, and blood tests to screen 50 ,138 adults aged 18 years or older taking part in a population-wide cardiovascular screening program., Results: Participants' mean age was 36.82 years (SD = 14.3); 43% were men. Risk factor prevalence rates were as follows: obesity, 35%; overweight, 32%; central obesity, 55%; diabetes, 18%; prediabetes, 27%; dyslipidemia, 44%; and hypertension, 23.1%. In addition, 26% of men were smokers, compared with 0.8% of women. Age-standardized diabetes and prediabetes rates were 25% and 30%, respectively, and age-standardized rates of obesity and overweight were 41% and 34%., Conclusions: This population-wide cardiovascular screening program demonstrated a high cardiovascular burden for our small sample in Abu Dhabi. The data form a baseline against which interventions can be implemented and progress monitored as part of the population-wide Abu Dhabi Cardiovascular Disease Program.

Objectives: The objectives of this study were to explore attitudes and beliefs among major national groups of women resident in the Emirate of Abu Dhabi (EAD) in relation to breast cancer screening and treatment., Design: A qualitative study utilizing age and nationality specific focus group discussions and interviews in all parts of EAD., Setting: Study was conducted among women living in various areas of EAD during April-September 2009., Participants: A total of 329 participants divided into four nationality groups and categorized into two functional groups (well women and regular screeners) were included in this study and participated in 46 focus groups and 30 personal interviews., Results: Some differences in beliefs, perceptions and opinions related to stated causes of breast cancer, preferences regarding breast care services, financial considerations, trust in health services and cultural attitudes towards breast cancer were observed across nationality and age groups., Conclusions: New information has been obtained that will shape more focused awareness messages, emphasizing on decreasing fear and shame, discouraging use of cauterization and herbal preparations in delaying care, and activating the role of older female peers in favor of breast screening. Ensuring a sufficient number of trained female health care providers and devising creative approaches to ensure preventive health care costs to reimburse non-nationals are structural changes to the health care system which may further improve breast health for all women in EAD.

This article discusses incentives to help make healthy choices the easy choices for individuals, operating at the levels of the individual, producers and service providers, and governments. Whereas paying individuals directly to be healthier seems to have a limited effect, offering financial incentives through health insurance improves health. Changing the environment to make healthier choices more accessible acts as an incentive to improve health. Employers can provide incentives to improve the health of their employees. Producers and service providers can take voluntary action to make their products less harmful, and they can be nudged into marketing healthier products within a regulatory environment. International agreements and monitoring systems can incentivize governments to do more for health. Lessons from climate change adaptation suggest that multilevel governance and policy integration are greater obstacles to policy change and implementation than knowing what has to be done. Policy change and implementation are triggered by many drivers, many of which are side effects of other policy pressures rather than of the direct policy goal itself. Effective action to reduce noncommunicable diseases will require leveraging social networks into a new ways of thinking about health; making better health prestigious and aspirational, and giving health and wellness a brand that encourages positive behavior change.

The depth and scale of challenges posed by noncommunicable diseases such as diabetes mellitus and cardiovascular disease are now well known and clearly documented. Reducing the 4 key risk factors has been shown to reduce premature mortality and morbidity by 70% globally. The authors consider how affirmative action can be driven to reduce these risk factors through Health Footprints, targeted interventions within specific domains of consumption, on the basis of an assessment of the negative health effect of specific choices, with the goal of driving healthy choices and improving health. In this article, the authors propose a methodology that ties together insight from public health, behavioral economics, marketing, and health communication. They offer 3 specific examples for affirmative action: a Pigovian tax on unhealthy foods, group-level interventions on the basis of sharing key health data, and personalized prevention tailored to specific individuals. In addition, they discuss the approach to implementation, including the role of an apex coordinating organization in setting standards for data and ethics, and evaluation of the effect of interventions to drive continuous improvement.

The Safety in the Heat program was developed in response to the extreme heat stress conditions experienced by workers in the United Arab Emirates and other Middle Eastern countries each summer, where ambient air temperatures often reach 45°C (135°F) and higher with 90% humidity. A comprehensive, multimedia, economical education and awareness program targeting companies in the region was developed; 465 companies employing 814 996 heat-exposed workers across 6254 work and labor residence sites were reached. Feedback from program participants indicated a high level of support and satisfaction. Results indicated a marked reduction in heat related illness over a period of 2 years (2008-2009) at 2 companies, one of which reported a combined 79.5% decrease in cases (15.3 vs 1.16 cases per 1000 workers) while the other experienced a 50% reduction in serious cases (0.08-0.04 cases per 100,000 work hours).

Intercellullar junctions formed by cadherins, including desmosomes and adherens junctions, comprise two dimensional arrays of "trans" dimers formed between monomers emanating from opposing cell surfaces. Lateral "cis" interfaces between cadherins from the same cell surface have been proposed to play a role in cadherin clustering. Although the molecular details of cis interactions remain uncertain, they must define an anisotropic arrangement where binding is favorable only in certain orientations. Here we report Monte Carlo simulations performed on a 2D lattice constructed to account for the anisotropy in cadherin cis interactions. A crucial finding is that the "phase transition" between freely diffusing cadherin monomers and dimers and a condensed ordered 2D junction formed by dimers alone is a cooperative process involving both trans and cis interactions. Moreover, cis interactions, despite being too weak to be measured in solution, are critical to the formation of an ordered junction structure. We discuss these results in light of available experimental information on cadherin binding free energies that are transformed from their bulk solution values to interaction energies on a 2D lattice.

Sixty years on from its first publication, the Framingham study has made an historic impact in risk identification and prediction of cardiovascular disease (CVD) burden globally. The challenge for the 21st century is in finding practical and scalable methods for effective implementation of population-level interventions that are adaptable to low-, middle-, and high-income settings. Within its first 2 years, the Abu Dhabi Cardiovascular Program, "Weqaya," has delivered a Framingham Risk Score for almost every adult Emirati. This is complemented by a clear and progressive program including the health sector and societal approach to the delivery of interventions for CVD. The health sector response includes the use of clear, evidence-based standards of clinical care, customer-focused service innovation such as the use of mobile and wellness clinics, and attention to the patient experience, and improving compliance using a mixture of encourage, enable, and enforce mechanics. Components of the Abu Dhabi societal approach include "top-down" measures to align the civil sector response including use of policies and regulation, for example, for trade and urban planning. The "bottom-up" measures aim to empower individuals, groups, and populations. Key to the success of this approach lies in central coordination and routine monitoring and evaluation, incorporating the use of simple, shared metrics. The Abu Dhabi approach has created a solid platform for scalable intervention, and for "learning by doing," with impact being monitored at the level of individuals, groups and the whole population. The unique data architecture in Abu Dhabi will enable the first cardiovascular risk score to be developed for the region and the incorporation of novel, modifiable risk factors into the model. The last 2 years have seen huge progress in Abu Dhabi for CVD, but the coming 5 to 10 years promise to unearth real, large-scale solutions, building on the original Framingham model. Furthermore, the Abu Dhabi model is scalable and adaptable to low- and middle-income country settings. Local and global data on CVD risk are stark and raise a clear challenge for public health; the time for clear actions has arrived., (Copyright 2010 Elsevier Inc. All rights reserved.)

Spontaneous Ca(2+) release from the sarcoplasmic reticulum (SR) appears to play an important role in cardiac sinoatrial node pacemaking. However, comparatively little is known about the role of intracellular Ca(2+) in the atrioventricular node (AVN). Intracellular Ca(2+) was therefore monitored in cells isolated from the rabbit AVN, using fluo-3 in conjunction with confocal microscopy. These cells displayed spontaneous Ca(2+) transients and action potentials. Ca(2+) transients were normally preceded by a small, slow increase (ramp) of intracellular Ca(2+) which was sometimes, but not always, accompanied by Ca(2+) sparks. During the Ca(2+) transient, intracellular [Ca(2+)] increased initially at the cell periphery and propagated inhomogeneously to the cell centre. The rate of spontaneous activity was decreased by ryanodine (1muM) and increased by isoprenaline (500nM); these changes were accompanied by a decrease and increase, respectively, in the slope of the preceding Ca(2+) ramp, with no significant change in Ca(2+) spark characteristics. Rapidly reducing bathing [Na(+)] inhibited spontaneous activity. These findings provide the first information on Ca(2+) handling at the sub-cellular level and link cellular Ca(2+) cycling to the genesis of spontaneous activity in the AVN.

For many years, we have known of deficits in our system of training mental health professionals, particularly in recognizing and integrating diversity. Recently, we have begun to understand that our literature must more authentically reflect the experiences of all people that we serve. The current paper suggests that a comprehensive biopsychosocial conceptualization of normal and abnormal behavior for all individuals is necessary to truly begin to reduce mental health disparities. The authors argue that factors such as racial, ethnic and cultural differences must be integrated into research before the literature will begin to change in a fashion that is beneficial to the mental health training process.

This study investigated the effect of betel quid chewing on the somatic motor pathway (Achilles tendon reflex time). The subjects, 48 healthy male volunteers, were divided into 4 groups: a control group; first-time chewers; occasional chewers; and habitual chewers. The Achilles reflex time (ART) of the subjects was taken 5 minutes after ingestion of the quid preparation and their pulse rate and respiratory rate were also recorded. The results show that betel quid chewing reduced the ART and increased the pulse rate and respiratory rate. It can be concluded that betel quid chewing causes a transient peripheral stimulation of the somatic motor pathway with a resultant hyperreflexia.

Background: Impairment of the protein C anticoagulation pathway is critical to the thrombosis associated with sepsis and to the development of purpura fulminans in meningococcemia. We studied the expression of thrombomodulin and the endothelial protein C receptor in the dermal microvasculature of children with severe meningococcemia and purpuric or petechial lesions., Methods: We assessed the integrity of the endothelium and the expression of thrombomodulin and the endothelial protein C receptor in biopsy specimens of purpuric lesions from 21 children with meningococcal sepsis (median age, 41 months), as compared with control skin-biopsy specimens., Results: The expression of endothelial thrombomodulin and of the endothelial protein C receptor was lower in the patients with meningococcal sepsis than in the controls, both in vessels with thrombosis and in vessels without thrombosis. On electron microscopical examination, the endothelial cells were generally intact in both thrombosed and nonthrombosed vessels. Plasma thrombomodulin levels in the children with meningococcal sepsis (median, 6.4 ng per liter) were higher than those in the controls (median, 3.6 ng per liter; P=0.002). Plasma levels, protein C antigen, protein S antigen, and antithrombin antigen were lower than those in the controls. In two patients treated with unactivated protein C concentrate, activated protein C was undetectable at the time of admission, and plasma levels remained low., Conclusions: In severe meningococcal sepsis, protein C activation is impaired, a finding consistent with down-regulation of the endothelial thrombomodulin-endothelial protein C receptor pathway.

The purpose of this study was to explore the nature of health insurance coverage research universities offer their employees and the extent to which these employers offer options providing for reimbursement of services of independent nurse practitioners. A request for health insurance documents mailed to 77 public research universities resulted in a response rate of 83 per cent. A total of 75 per cent sent usable descriptions of insurance coverage for analysis. Among the respondents, 69 per cent (n = 40) reported offering insurance through Blue Cross/Blue Shield companies. Nursing services reimbursed generally included traditional nursing care such as private duty nursing and home health care. Coverage of nursing services that overlap with traditional medical practice, such as prenatal care and labor and delivery services of nurse midwives, anesthesia services of nurse anesthetists, psychiatric services of nurse specialists, and primary care nursing services of nurse practitioners, was less evident. Findings generally indicated that in spite of the presence of enabling or mandatory state legislation for third-party reimbursement of nursing services, legislation is not being implemented in many states by employers in their purchase of group policies.

1. The major milk proteins synthesized by the lactating mammary gland of the guinea pig were identified and designated as caseins A, B and C and alpha-lactalbumin, with estimated mol.wts. of 28000, 25500, 20500 and 14500 respectively. 2. Antisera to the total casein fraction and to alpha-lactalbumin were prepared from rabbits. The milk proteins were also iodinated with either 131I or 125I. 3. A poly(A)-rich RNA fraction was isolated from lactating guinea-pig mammary glands. Isolation was by affinity chromatography on oligo(dT)-cellulose. 4. Examination of this RNA fraction by electrophoresis on polyacrylamide gels containing formamide indicated three major species 1, 2 and 3, with estimated wol.wts. of 5.4 X 10(5) and 3.3 X 10(5), and the apparent absence of rRNA species. 5. The poly(A)-rich RNA stimulated protein synthesis in heterologous cell-free systems based on wheat germ, Krebs II ascites-tumour cells, and the latter supplemented with an initiation factor-3 fraction from rabbit reticulocyte ribosomes. 6. Between 80 and 90% of the protein synthesis directed by the mRNA was for milk proteins. 7. Analysis of the proteins immunoprecipitated by the alpha-lactalbumin antiserum showed in the wheat-germ system that the product was a protein with a molecular weight greater than that of alpha-lactalbumin, whereas in the ascites-tumour-cell systems both this protein and alpha-lactalbumin were found. When the larger protein was treated with CNBr and the resulting peptides were examined, it was shown that the extra peptide was at the N-terminus. This and other evidence is adduced for the initial translation product of alpha-lactalbumin being a precursor with an addition of about ten amino acids at the N-terminus. 8. Similar analysis of the casein immlnospecific proteins produced under the direction of mRNA indicated that the products had a molecular weight that was apparently a littel smaller than that of the caseins synthesized in vivo. This was not consistent with higher-molecular weight casein precursors. 9. Possible explanations for the results obtained are discussed, especially in terms of the physiological significance of the pre-alpha-lactalbumin as a secretory protein.

Achievement tests, whether cognitive or performance, often are not analyzed with the intent of detecting subtests within the total test. Subtests should represent unitary concepts. A step-by-step process for detecting subconcepts is proposed and exemplified. Concepts arrived at by the proposed methodology can provide insight to learner strategies for learning and can refine outcome measures to detect effects of the independent variable in teaching-learning investigations.