Role of single nucleotide polymorphism rs2383206 on coronary artery disease risk among Saudi Population: a case-control study.

OBJECTIVE: We aim to investigate the relationship between genetic variation and biological function on a genomic scale, focusing on identifying genes responsible for complex diseases using single nucleotide polymorphisms. Specifically, the study explores the association between the rs2383206 gene located on chromosome 9p21.3 and the development of coronary artery disease (CAD) in a specific Saudi population. PATIENTS AND METHODS: This case-control study was conducted between September 2013 and May 2015 at King Abdullah Medical City (KAMC) and Al-Noor Specialist Hospital targeting the Saudi Population residing in the western region of Saudi Arabia. The study enrolled 315 cases with documented CAD and 205 controls with normal coronary arteries on coronary angiography. Genomic DNA was extracted from peripheral blood samples of both groups, and genotyping of rs2383206 was performed using the tetra-primer amplification-refractory mutation system-polymerase chain reaction (ARMS-PCR) method. RESULTS: In this study, the prevalence of the GG genotype in rs2383206 was found to be higher in patients with CAD than in controls, with an odds ratio of 1.997 [95% confidence interval (CI): 1.176-3.394, p = 0.007]. Additionally, individuals with the GG genotype who had sedentary lifestyles, hyperlipidemia, and smoked were found to be at a higher risk for developing CAD (p = 0.003, 0.009, and 0.003, respectively). The G allele also increased the risk of CAD with an odds ratio of 1.413 (95% CI: 1.099-1.817; p = 0.004). CONCLUSIONS: In conclusion, this study demonstrated a significant association between the rs2383206 variant located on chromosome 9p21 and the development of CAD. The findings of this study provide valuable insights into the genetic susceptibility to CAD and highlight the potential of this variant as a target for future functional studies.

Methylene blue versus vasopressin analog for refractory septic shock in the preterm neonate: A randomized controlled trial.

BACKGROUND: Refractory septic shock in neonates is still associated with high mortality, necessitating an alternative therapy, despite all currently available treatments. This study aims to assess the vasopressor effect of methylene blue (MB) in comparison to terlipressin (TP) as adjuvant therapy for refractory septic shock in the preterm neonate. METHODS: A double-blinded randomized controlled trial was conducted in the Neonatal Intensive Care Units at Ain Shams University, Egypt. Thirty preterm neonates with refractory septic shock were randomized to receive either MB or TP as an adjuvant to conventional therapy. Both MB and TP were administered as an intravenous loading dose followed by continuous intravenous infusion. The hemodynamic variables, functional echocardiographic variables, and oxidant stress marker were assessed over a 24 h period together with the side effects of MB. RESULTS: MB causes significant improvement in mean arterial blood pressure with a significant decrease of the norepinephrine requirements (1.15±0.21µm/kg/min at baseline vs. 0.55±0.15µm/kg/min at 24 h). MB infusion causes an increase of the pulmonary pressure (44.73±8.53 mmHg at baseline vs. 47.27±7.91 mmHg after 24 h) without affecting the cardiac output. Serum malonaldehyde decreased from 5.45±1.30 nmol/mL at baseline to 4.40±0.90 nmol/mL at 24 h in the MB group. CONCLUSION: Administration of MB to preterm infants with refractory septic shock showed rapid increases in systemic vascular resistance and arterial blood pressure with minimal side effects.

Increased cardiovascular comorbidities in patients with myelodysplastic syndromes and chronic myelomonocytic leukemia presenting with systemic inflammatory and autoimmune manifestations.

Myelodysplastic syndromes (MDS) and associated diseases, like chronic myelomonocytic leukemias (CMML), are heterogeneous, clonal disorders affecting the hematopoietic stem cells. They are characterized by dysplasia and a propensity to evolve toward acute myeloid leukemia. Systemic inflammatory and autoimmune manifestations (SIAMs) occur with a prevalence of 10% to 20% in myeloid malignancies, but the underlying pathogenetic mechanisms remain obscure. In this study, we aimed to characterize patient- and disease-based differences in MDS and CMML patients with and without SIAMs and explore the impact of SIAMs on progression and survival. We performed a retrospective, single-centre, and case-control study in a cohort of 93 patients diagnosed with MDS and CMML between 01/2008 and 12/2015. Thirty patients (32%) were identified with SIAMs: musculoskeletal and connective tissue (26.8%), vascular (19.5%), systemic autoinflammation (17%), skin (12.2%), gastrointestinal (9.8%), and others (14.6%). SIAMs were treated with glucocorticoids (60%), methotrexate (16.7%), biologicals (13.3%), and cyclosporine (3.3%). No significant differences between the SIAM and non-SIAM patients were observed in age, gender, or previous exposure to cancer treatment. Cardiovascular comorbidities were significantly more frequent in patients with SIAMs (63.1% vs 90%; OR 5.5; P < .01), but no differences were observed for other comorbidities or IPSS and IPSS-R risk scores. CMML and refractory anemia with excess blasts 1/2 subtypes were by tendency more frequent in patients with and refractory cytopenia with multilineage dysplasia (RCMD) in those without SIAMs. Finally, time to progression, leukemia free survival and overall survival were similar for both groups. Despite patient heterogeneity and small cohort size, we were able to identify a significant association of SIAMs with cardiovascular comorbidities but without influence on progression or survival.

Pre-exposure prophylaxis: awareness, acceptability and risk compensation behaviour among men who have sex with men and the transgender population.

OBJECTIVES: This exploratory study examined the facilitators of and barriers to acceptance of pre-exposure prophylaxis (PrEP) and potential risk compensation behaviour emerging from its use among men who have sex with men (MSM) and transgender individuals (TGs) in India. METHODS: A questionnaire was administered to 400 individuals registered with a targeted intervention programme. Logistic regression models were used to identify facilitators of and barriers to PrEP acceptance. RESULTS: The respondents consisted of 68% MSM and 32% TGs. Risk behaviour categorization identified 40% as low risk, 41% as medium risk and, 19% as high risk for HIV infection. About 93% of the respondents were unaware of PrEP, but once informed about it, 99% were willing to use PrEP. The facilitators of PrEP acceptance were some schooling [odds ratio (OR) 2.16; P = 0.51], being married or in a live-in relationship (OR 2.08; P = 0.46), having a high calculated risk (OR 3.12; P = 0.33), and having a high self-perceived risk (OR 1.8; P = 0.35). Increasing age (OR 2.12; P = 0.04) was a significant barrier. TGs had higher odds of acceptance of PrEP under conditions of additional cost (OR 2.12; P = 0.02) and once-daily pill (OR 2.85; P = 0.04). Individuals identified as low risk for HIV infection showed lower odds of potential risk compensation, defined as more sexual partners (OR 0.8; P = 0.35), unsafe sex with new partners (OR 0.71; P = 0.16), and decreased condom use with regular partners (OR 0.95; P = 0.84), as compared with medium-risk individuals. The associations, although not statistically significant, are nevertheless important for public health action given the limited scientific evidence on PrEP use among MSM and TGs in India. CONCLUSIONS: With high acceptability and a low likelihood of risk compensation behaviour, PrEP can be considered as an effective prevention strategy for HIV infection among MSM and TGs in India.

Quality of death notification forms in North West Bank/Palestine: a descriptive study.

BACKGROUND: The death notification forms (DNFs) are important documents. Thus, inability to fill it properly by physicians will affect the national mortality report and, consequently, the evidence-based decision making. The errors in filling DNFs are common all over the world and are different in types and causes. We aimed to evaluate the quality of DNFs in terms of completeness and types of errors in the cause of death section. METHODS: A descriptive study was conducted to review 2707 DNFs in North West Bank/Palestine during the year 2012 using data abstraction sheets. SPSS 17.0 was used to show the frequency of major and minor errors committed in filling the DNFs. RESULTS: Surprisingly, only 1% of the examined DNFs had their cause of death section filled completely correct. The immediate cause of death was correctly identified in 5.9% of all DNFs and the underlying cause of death was correctly reported in 55.4% of them. The sequence was incorrect in 41.5% of the DNFs. The most frequently documented minor error was "Not writing Time intervals" error (97.0%). CONCLUSION: Almost all DNFs contained at least one minor or major error. This high percentage of errors may affect the mortality and morbidity statistics, public health research and the process of providing evidence for health policy. Training workshops on DNF completion for newly recruited employees and at the beginning of the residency program are recommended on a regular basis. As well, we recommend reviewing the national DNFs to simplify it and make it consistent with updated evidence-based guidelines and recommendation.

Fractional carbon dioxide laser versus low-dose UVA-1 phototherapy for treatment of localized scleroderma: a clinical and immunohistochemical randomized controlled study.

Morphea is a rare fibrosing skin disorder that occurs as a result of abnormal homogenized collagen synthesis. Fractional ablative laser resurfacing has been used effectively in scar treatment via abnormal collagen degradation and induction of healthy collagen synthesis. Therefore, fractional ablative laser can provide an effective modality in treatment of morphea. The study aimed at evaluating the efficacy of fractional carbon dioxide laser as a new modality for the treatment of localized scleroderma and to compare its results with the well-established method of UVA-1 phototherapy. Seventeen patients with plaque and linear morphea were included in this parallel intra-individual comparative randomized controlled clinical trial. Each with two comparable morphea lesions that were randomly assigned to either 30 sessions of low-dose (30 J/cm2) UVA-1 phototherapy (340-400 nm) or 3 sessions of fractional CO2 laser (10,600 nm-power 25 W). The response to therapy was then evaluated clinically and histopathologically via validated scoring systems. Immunohistochemical analysis of TGF-ß1 and MMP1 was done. Patient satisfaction was also assessed. Wilcoxon signed rank test for paired (matched) samples and Spearman rank correlation equation were used as indicated. Comparing the two groups, there was an obvious improvement with fractional CO2 laser that was superior to that of low-dose UVA-1 phototherapy. Statistically, there was a significant difference in the clinical scores (p = 0.001), collagen homogenization scores (p = 0.012), and patient satisfaction scores (p = 0.001). In conclusion, fractional carbon dioxide laser is a promising treatment modality for cases of localized morphea, with proved efficacy of this treatment on clinical and histopathological levels.

Marshall syndrome: further evidence of a distinct phenotypic entity and report of new findings.

Marshall syndrome and type II Stickler syndrome are caused by mutations in COL11A1, which codes for the proα1chain of collagen XI. Collagen XI is a minor fibrillar collagen co-expressed with collagen II in cartilage and the vitreous of the eye. Characteristic features of Marshall syndrome include midfacial hypoplasia, high myopia, and sensorineural-hearing deficit. Deletions, insertions, splice site, and missense mutations in COL11A1 have been identified in Stickler syndrome and Marshall syndrome patients. In this study, we describe the clinical presentations of seven patients with Marshall syndrome from three unrelated Saudi families, inherited as autosomal dominant (two families) and autosomal recessive (one family). Cardinal clinical features of Marshall syndrome are manifested in all patients. One patient had ectodermal abnormalities. Mutations (c.2702G > A in exon 34,IVS50 + 1G > A, and IVS50 + lG > C) were identified in COL11A1 in affected members. Interestingly, the first report of autosomal recessive Marshall syndrome was from Saudi Arabia caused by the same mutation (c.2702G > A, p.Gly901Glu) as in one of our families. This study depicts detailed phenotypic and genetic description of dominant and recessive forms of Marshall syndrome due to COL11A1 mutations.

Novel PHKG2 mutation causing GSD IX with prominent liver disease: report of three cases and review of literature.

Glycogen storage disease type IX (GSD IX) is a common form of glycogenosis due to mutations in PHKA1, PHKA2, or PHKB and PHKG2 genes resulting in the deficiency of phosphorylase kinase. The first two genes are X-linked while the latter two follow an autosomal recessive inheritance. The majority of cases of GSD IX are attributed to defects in PHKA2 which usually cause a mild disease. We report three patients with PHKG2-related GSD IX presenting with significant hepatic involvement, fibrosis, and cirrhosis. Interestingly, the homozygosity mapping resolved a dilemma about an erroneously normal phosphorylase kinase activity in patient 1. The novel mutation found in all the three patients (p.G220E) affects the catalytic subunit of the phosphorylase kinase. Increasing evidence shows that patients with PHKG2 mutations have a severe hepatic phenotype within the heterogeneous GSD IX disorder. Therefore, defect in PHKG2 should be considered in patients with suspected glycogenosis associated with significant liver fibrosis and cirrhosis.

Hypercalcaemia in rheumatoid arthritis: investigation of its causes and implications.

When correction was made for hypoalbuminaemia, 23 of 50 ambulant patients with definite or classical rheumatoid arthritis were found to have hypercalcaemia. When these 23 patients were studied 6 months later, 7 had hypercalcaemia as defined by the correction factor for a low serum albumin level, and 6 of these patients had raised serum ionised calcium concentrations. Biochemical studies in the 23 patients indicated evidence of hyperparathyroidism, namely, hypophosphataemia, increased serum alkaline phosphatase, hyperchloraemia, and reduced tubular reabsorption of calcium. However, serum immunoreactive parathyroid hormone concentrations were normal. Only one patient had an abnormally low serum 25-hydroxy-vitamin D result: this patient had a high level of urinary D-glucaric acid and was receiving phenobarbitone for treatment of epilepsy. The biochemical features suggestive of parathyroid overactivity were particularly found in patients with raised serum calcium levels. The cause of hypercalcaemia in rheumatoid arthritis remains to be explained.