Search

Background: Hypertension is considered the most important risk factor for cardiovascular diseases, but its control is poor worldwide. We aimed to assess the availability and affordability of blood pressure-lowering medicines, and the association with use of these medicines and blood pressure control in countries at varying levels of economic development. Methods: We analysed the availability, costs, and affordability of blood pressure-lowering medicines with data recorded from 626 communities in 20 countries participating in the Prospective Urban Rural Epidemiological (PURE) study. Medicines were considered available if they were present in the local pharmacy when surveyed, and affordable if their combined cost was less than 20% of the households' capacity to pay. We related information about availability and affordability to use of these medicines and blood pressure control with multilevel mixed-effects logistic regression models, and compared results for high-income, upper-middle-income, lower-middle-income, and low-income countries. Data for India are presented separately because it has a large generic pharmaceutical industry and a higher availability of medicines than other countries at the same economic level. Findings: The availability of two or more classes of blood pressure-lowering drugs was lower in low-income and middle-income countries (except for India) than in high-income countries. The proportion of communities with four drug classes available was 94% in high-income countries (108 of 115 communities), 76% in India (68 of 90), 71% in upper-middle-income countries (90 of 126), 47% in lower-middle-income countries (107 of 227), and 13% in low-income countries (nine of 68). The proportion of households unable to afford two blood pressure-lowering medicines was 31% in low-income countries (1069 of 3479 households), 9% in middle-income countries (5602 of 65 471), and less than 1% in high-income countries (44 of 10 880). Participants with known hypertension in communities that had all four drug classes available were more likely to use at least one blood pressure-lowering medicine (adjusted odds ratio [OR] 2·23, 95% CI 1·59–3·12); p

Competing Interests: The authors have no funding or conflicts of interest to disclose.

Objectives: To determine the incidence of newborn screening (NBS) disorders and to study the key performance indicators of the program., Methods: This retrospective single-center study enrolled all infants who underwent NBS from January 2012 to December 2017 at Prince Sultan Military Medical City, Riyadh, Saudi Arabia. We screened 17 NBS disorders. Blood samples were collected 24 hours after birth. If the initial result was positive, a second sample was collected. True positive cases were immediately referred for medical management. Data were extracted from laboratory computerized and non-computerized records using case report forms., Results: During the study period, 56632 infants underwent NBS with a coverage rate of 100%. Thirty-eight cases were confirmed. The incidence of congenital hypothyroidism was 1:3775. The positive predictive value for the detection of congenital hypothyroidism was 11.8%. Propionic aciduria was the most common metabolic disorder, with an incidence of 1:14158. Very long-chain acyl CoA dehydrogenase deficiency and glutaric aciduria type 1 had an incidence of 1:18877 each. Phenylketonuria, biotinidase deficiency, maple syrup urine disease, and citrullinemia had an incidence of 1:28316 each. However, galactosemia and 3-methyl crotonyl carboxylase deficiency had the lowest incidence of 1:56632., Conclusion: The NBS coverage rate at our facility was 100%. Congenital hypothyroidism was the most frequently detected disorder with an incidence that matches worldwide figures. The incidence of other inherited disorders was consistent with regional figures.

Obesity is associated with the production of inflammatory cytokines that are implicated in insulin resistance (IR), and if not addressed, can lead to type 2 diabetes (T2D). The role of the immune system in skeletal muscle (SM) inflammation and insulin sensitivity is not yet well characterized. As SM IR is an important determinant of glycaemia, it is critical that the muscle-immune phenotype is mapped to help design interventions to target T2D. This systematic review synthesized the evidence for SM macrophage content and phenotype in humans and murine models of obesity, and the association of muscle macrophage content and phenotype with IR. Results were synthesized narratively, as we were unable to conduct a meta-analysis. We included 28 studies (n=10 human, n=18 murine), and all studies detected macrophage markers in SM. Macrophage content was positively associated with IR. In humans and mice, there was variability in muscle macrophage content and phenotype in obesity. Overall certainty in the evidence was low due to heterogeneity in detection methods and incompleteness of data reporting. Macrophages are detected in human and murine SM in obesity and a positive association between macrophage content and IR is noted; however, the standardization of markers, detection methods, and reporting of study details is warranted to accurately characterize macrophages and improve the potential for creating specific and targeted immune-based therapies in obesity., (© 2019 World Obesity Federation.)

Nonsteroidal anti-inflammatory drugs have been shown to reduce the incidence of gastrointestinal cancers, but the propensity of these drugs to cause ulcers and bleeding limits their use. H2S has been shown to be a powerful cytoprotective and anti-inflammatory substance in the digestive system. This study explored the possibility that a H2S-releasing nonsteroidal anti-inflammatory drug (ATB-346) would be effective in a murine model of hereditary intestinal cancer (APCMin+ mouse) and investigated potential mechanisms of action via transcriptomics analysis. Daily treatment with ATB-346 was significantly more effective at preventing intestinal polyp formation than naproxen. Significant beneficial effects were seen with a treatment period of only 3-7 days, and reversal of existing polyps was observed in the colon. ATB-346, but not naproxen, significantly decreased expression of intestinal cancer-associated signaling molecules (cMyc, β-catenin). Transcriptomic analysis identified 20 genes that were up-regulated in APCMin+ mice, 18 of which were reduced to wild-type levels by one week of treatment with ATB-346. ATB-346 is a novel, gastrointestinal-sparing anti-inflammatory drug that potently and rapidly prevents and reverses the development of pre-cancerous lesions in a mouse model of hereditary intestinal tumorigenesis. These effects may be related to the combined effects of suppression of cyclooxygenase and release of H2S, and correction of most of the APCMin+-associated alterations in the transcriptome. ATB-346 may represent a promising agent for chemoprevention of tumorigenesis in the GI tract and elsewhere.

Hydrogen sulfide exerts a number of cytoprotective and anti-inflammatory effects in many organ systems. In an effort to exploit these potent and beneficial effects, a number of hydrogen sulfide-releasing derivatives of existing drugs have been developed and extensively tested in pre-clinical models. In particular, efforts have been made by several groups to develop hydrogen sulfide-releasing derivatives of a number of nonsteroidal anti-inflammatory drugs. The main goal of this approach is to reduce the gastrointestinal ulceration and bleeding caused by this class of drugs, particularly when used chronically such as in the treatment of arthritis. However, these drugs may also have utility for prevention of various types of cancer. This paper provides an overview of some of the mechanisms underlying the anti-inflammatory and cytoprotective actions of hydrogen sulfide. It also gives some examples of hydrogen sulfide-releasing anti-inflammatory drugs, and their actions in terms of reducing inflammation and attenuating the development of cancer in experimental models., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Significance: There is a rapidly expanding body of evidence for important roles of hydrogen sulfide in protecting against tissue injury, reducing inflammation, and promoting repair. There is also growing evidence that H2S can be successfully exploited in drug development., Recent Advances: H2S synthesis and degradation are regulated in circumstances of inflammation and injury so as to promote repair and re-establish homeostasis. Novel H2S-releasing drugs exhibit enhanced anti-inflammatory and pro-restorative effects, while having reduced adverse effects in many tissues., Critical Issues: H2S is a pleiotropic mediator, having effects on many elements in the inflammatory cascade and promoting the resolution of inflammation and injury. It also contributes significantly to mucosal defence in the gastrointestinal tract, and in host defence against infection. There is strong evidence that novel, H2S-based therapeutics are safe and effective in animal models, and several are progressing through human trials., Future Directions: A better understanding of the physiological and pathophysiological roles of H2S continues to be restrained by the lack of simple, reliable methods for measurement of H2S synthesis, and the paucity of highly selective inhibitors of enzymes that participate in endogenous H2S synthesis. On the other hand, H2S donors show promise as therapeutics for several important indications.

Background: For decades we have understood the risk factors for suicide in the general population but have fallen short in understanding what distinguishes the risk for suicide among patients with serious psychiatric conditions., Aims: This prompted us to investigate risk factors for suicidal behavior among psychiatric inpatients., Method: We reviewed all psychiatric hospital admissions (2008-2011) to a centralized psychiatric hospital in Ontario, Canada. Using multivariable logistic regression we evaluated the association between potential risk factors and lifetime history of suicidal behavior, and constructed a model and clinical risk score to predict a history of this behavior., Results: The final risk prediction model for suicidal behavior among psychiatric patients (n = 2,597) included age (in three categories: 60-69 [OR = 0.74, 95% CI = 0.73-0.76], 70-79 [OR = 0.45, 95% CI = 0.44-0.46], 80+ [OR = 0.31, 95% CI = 0.30-.31]), substance use disorder (OR = 1.30, 95% CI = 1.27-1.32), mood disorder (OR = 1.49, 95% CI = 1.47-1.52), personality disorder (OR = 2.30, 95% CI = 2.25-2.36), psychiatric disorders due to general medical condition (OR = 0.52, 95% CI = 0.50-0.55), and schizophrenia (OR = 0.42, 95% CI = 0.41-0.43). The risk score constructed from the risk prediction model ranges from -9 (lowest risk, 0% predicted probability of suicidal behavior) to +5 (highest risk, 97% predicted probability)., Conclusion: Risk estimation may help guide intensive screening and treatment efforts of psychiatric patients with high risk of suicidal behavior.

Regular use of nonsteroidal anti-inflammatory drugs is associated with a significantly lower incidence of several types of cancer, particularly those affecting the gastrointestinal tract. However, the propensity of these drugs to cause ulcers and bleeding in the stomach and small intestine limits their utility for chemoprevention of cancer. In the present study, we evaluated the effectiveness of a novel hydrogen sulfide-releasing derivative of naproxen in reducing the incidence of pre-cancerous lesions (aberrant crypt foci) in mice treated with the carcinogen azoxymethane. Weekly administration of azoxymethane over a 4-week period resulted in formation of an average of ∼50 aberrant crypt foci in the colon. Twice-daily treatment with naproxen at high doses significantly reduced the number of aberrant crypt foci. However, a significantly greater effect was observed with ATB-346 (H2S-releasing naproxen) and it was also effective at much lower doses, where naproxen was ineffective. The H2S-releasing moiety of ATB-346 did not significantly affect the number of aberrant crypt foci, suggesting that both the inhibition of cyclooxygenase activity and release of H2S were necessary for the enhanced chemopreventative effect. ATB-346 suppressed colonic prostaglandin synthesis and whole blood thromboxane synthesis as effectively as naproxen, but did not induce any gastrointestinal injury. These results demonstrate that ATB-346 exerts superior chemopreventive effects to those of naproxen, while sparing the gastrointestinal tract of the injury normally associated with use of the parent drug. ATB-346 may therefore be an attractive agent for chemoprevention of colon cancer, and possibly of cancers in other tissues., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Serotonin is a widely investigated neurotransmitter in several psychopathologies, including suicidal behavior (SB); however, its role extends to several physiological functions involving the nervous system, as well as the gastrointestinal and cardiovascular systems. This review summarizes recent research into ten serotonergic genes related to SB. These genes - TPH1, TPH2, SLC6A4, SLC18A2, HTR1A, HTR1B, HTR2A, DDC, MAOA, and MAOB - encode proteins that are vital to serotonergic function: tryptophan hydroxylase; the serotonin transporter 5-HTT; the vesicular transporter VMAT2; the HTR1A, HTR1B, and HTR2A receptors; the L-amino acid decarboxylase; and the monoamine oxidases. This review employed a systematic search strategy and a narrative research methodology to disseminate the current literature investigating the link between SB and serotonin.

Dextran sulfate sodium is widely used to induce colitis in rodents. Though given orally in drinking water, this agent is widely believed to produce injury through direct toxic effects on the epithelium, and it has been assumed to produce damage and inflammation only in the colon. Given the apparent toxic effects of dextran sodium sulfate on epithelial cells, its administration orally, and the anticoagulant properties of this agent, we hypothesized that significant damage and inflammation would be produced in regions of the digestive tract proximal to the colon. Groups of rats or mice received DSS (5%) in the drinking water for up to 7 days. Tissues were harvested at various time-points for blind evaluation of damage, and measurement of several markers of inflammation. In both rats and mice given DSS, significant damage and inflammation was produced in the stomach, small intestine and colon. Significant granulocyte infiltration was apparent in all tissues by day 3 of DSS ingestion. Bleeding was evident throughout the small intestine and colon. These studies clearly demonstrate that DSS, when administered orally in drinking water, produces a pan-gastroenteritis, rather than the damage and inflammation being limited to the colon. The damage and inflammation in the stomach and small intestine could contribute to changes in body weight, stool consistency and bleeding, all of which are commonly used as indices of severity of colitis. Beneficial or detrimental effects of therapeutic interventions could be attributable, at least in part, to modulation of injury and inflammation proximal to the colon.