Novel PIK3R1 gene mutation associated with SHORT syndrome: a case report of a 15-year-old female.

OBJECTIVES: To present the clinical journey and management of a 15-year-old female with SHORT syndrome, highlighting the diagnostic challenges and the novel genetic mutation identified. CASE PRESENTATION: A 15-year-old Filipino female was initially seen in a dermatology clinic at 9 years old for axillary skin darkening, indicative of acanthosis nigricans. Early evaluations revealed elevated blood glucose levels, resulting in a pediatric diabetes diagnosis without the usual hyperglycemic symptoms. Her medical history was notable for premature birth, intrauterine growth restriction, a cardiac murmur from patent ductus arteriosus and a bicuspid aortic valve, delayed teething, and distinct dysmorphic features. Genetic testing identified a novel PIK3R1 gene mutation. Treatment with Metformin significantly improved her glycemic control and lipid profiles. The patient also displayed delayed puberty and polycystic ovary syndrome-like symptoms, but growth hormone deficiency was excluded. Endocrine evaluation for her short stature and lipodystrophy confirmed the presence of the PIK3R1 mutation. CONCLUSIONS: This case highlights the importance of thorough endocrine and genetic evaluations in patients with complex clinical presentations like SHORT syndrome. The identification of a novel PIK3R1 gene mutation expands the understanding of the genetic basis of this syndrome and underscores the need for individualized treatment approaches.

Demographical and population dynamics impact on public health of cutaneous Leishmaniasis in Al-Madinah Almonawra, Saudi Arabia.

BACKGROUND: A cross-sectional study conducted in Al-Madinah Almonawra in KSA held during the period from March 2014-March 2015. AIM OF THE STUDY: This study aimed at analyzing the effect of population dynamics on the current situation of cutaneous leishmaniasis in Al-Madinah Almonawarah area, a holy city that attracts millions of muslims annually. METHODOLOGY: Epidemiological and clinical data were collected by especial questionnaire and laboratory specimens were collected using skin scraping and needle aspiration. Staining and direct microscopy were done. LST was conducted. Analysis was done using SPSS program. RESULTS: The study included 164 patients, all of them were men. Saudi nationality comprised around 20% of the study group, the majority were Egyptians, 26.2%, followed by Pakistani, 21.3%. CONCLUSION: The presence of non-Saudi nationality as foreign workers, immigrants and refugees has worsened the current situation of the disease.

Early rescue Neopuff for infants with transient tachypnea of newborn: a randomized controlled trial.

OBJECTIVE: To examine the efficacy of early continuous positive airway pressure (CPAP), delivered using a T-piece-based infant resuscitator (Neopuff) via a face mask, in reducing the severity and duration of transient tachypnea of the newborn (TTN) as well as testing a hypothesis suggesting that rapid clearance of fetal lung fluid to the circulation via CPAP would increase plasma B-type natriuretic peptide (BNP). METHODS: A randomized controlled trial (NCT01859533) was conducted on 64 late preterm/term neonates, delivered by cesarean section and presented by respiratory distress shortly after birth. The Neopuff group included 34 neonates received 20 min of early CPAP and control group included 30 neonates received free flow O2. Plasma BNP was measured baseline and 2 h later. RESULTS: The duration of tachypnea was shorter in Neopuff group with less need of neonatal intensive care unit admission and need of mechanical support (p < .05) with no effect on duration of hospitalization (p > .05). Plasma BNP showed no significant difference between pre- and post-Neopuff levels (p > .05). A positive correlation was found between BNP and duration of tachypnea as well as the length of hospitalization (p < .05) among Neopuff group. CONCLUSION: Early rescue CPAP reduces the duration and severity of respiratory distress among infants with TTN.

Genetic characteristics, clinical spectrum, and incidence of neonatal diabetes in the Emirate of AbuDhabi, United Arab Emirates.

Neonatal diabetes mellitus (NDM) can be transient (TNDM) or permanent (PNDM). Data on NDM from the Gulf region are limited to few studies on PNDM.The objective of this study was to describe the genetic and clinical spectrum of NDM and estimate its incidence in AbuDhabi, capital of the United Arab Emirate (UAE). Patients were identified from the pediatric diabetes clinics and sequencing of known NDM genes was conducted in all families. Twenty-five patients were identified. Incidence during 1985-2013 was 1:29,241 Live births. Twenty-three out of twenty-five had PNDM (incidence 1:31,900) and 2/25 had TNDM (incidence 1:350,903). Eleven out of twenty-five had extra-pancreatic features and three had pancreatic aplasia. The genetic cause was detected in 21/25 (84%). Of the PNDM patients, nine had recessive EIF2AK3 mutations, six had homozygous INS mutations, two with deletion of the PTF1A enhancer, one was heterozygous for KCNJ11 mutation, one harboured a novel ABCC8 variant, and 4/21 without mutations in all known PNDM genes. One TNDM patient had a 6q24 methylation defect and another was homozygous for the INS c-331C>G mutation. This mutation also caused permanent diabetes with variable age of onset from birth to 18 years. The parents of a child with Wolcott-Rallison syndrome had a healthy girl following pre-implantation genetic diagnosis. The child with KCNJ11 mutation was successfully switched from insulin to oral sulphonylurea. The incidence of PNDM in Abu Dhabi is among the highest in the world and its spectrum is different from Europe and USA. In our cohort, genetic testing has significant implications for the clinical management.

Comprehensive study on laboratory biomarkers for prediction and diagnosis of deep venous thrombosis.

Deep venous thrombosis (DVT) is based upon clinical suspicion in patients at risk and confirmatory duplex imaging of the deep venous system of the affected extremity. The aim of the present study was to determine different cutoff points of D-dimer, P-selectin and microparticles that could be used in early diagnosis and prediction of impending DVT in symptomatic patients with normal duplex ultrasound. Three groups of individuals were examined: 50 healthy volunteers (Group I); 75 patients with positive duplex ultrasound for DVT (Group II) and 75 symptomatic patients, but with negative duplex ultrasound for DVT (Group III). D-dimer was measured by immunoturbidimetric assay, P-selectin by flow cytometry and microparticles by ELISA. D-dimer, P-selectin and microparticles levels were significantly higher in Group II and III patients when compared with Group I individuals. Using receiver-operating characteristic curves, we determined that cutoff levels of 0.92 mg/l for D-dimer, 17.8% for P-selectin and 16.5 nmol/l for microparticles can accurately rule out DVT. New cutoff levels were estimated for the three studied biomarkers that differentiated the group of DVT-negative duplex patients without thrombosis from those patients of the same group who developed thrombosis being 2.81 mg/l for D-dimer, 30.2% for P-selectin and 26 nmol/l for microparticles. D-dimer, P-selectin and microparticles can be used to diagnose and detect impending DVT, thus identifying patients at high risk that could benefit from early anticoagulant therapy without the need for imaging studies.

Maternal knowledge and use of folic acid among Saudi females.

OBJECTIVE: To explore and find out the level of awareness regarding folic acid's (FAs) importance, current use, and timing of administration among pregnant Saudi females. METHODS: This is a cross-sectional study conducted randomly among women aged 18-45 years old, attending the Antenatal and Gynecology Clinics at the Maternity and Children's Hospital, Al-Qassim, Kingdom of Saudi Arabia from January to November 2012. A total of 1250 subjects were approached, and 1000 women expressed their verbal consent to participate. The questionnaire consisted of 17 items, and results were analyzed using univariate and multivariate analysis. RESULTS: A total of 88.4% of women were aware of FA. However, only 4.4% of them took FA before pregnancy. Compared to highly educated women (20.4%), only 5% of illiterate women use FA during the first trimester of their pregnancy. Univariate and multivariate analysis showed that educational level had a significant association with FA awareness and use (p=0.001; odds ratio: 0.000; 95% confidence interval: 1.001 to 1.080). Most women recall hearing of FA from their doctors. Only 48 women reported a history of a previous child with congenital anomalies, and 4 of them (8.3%) of them used FA before pregnancy. CONCLUSION: We found that only 4.4% of the studied women use FA in their preconceptional period. The higher the educational level, the more the knowledge, and frequent use of FA. Poor level of awareness among lower educated woman requires medical authorities to broadcast the importance of FA, and there may be a need to fortify food with FA.

Identification of two distinct carcinoma-associated fibroblast subtypes with differential tumor-promoting abilities in oral squamous cell carcinoma.

Heterogeneity of carcinoma-associated fibroblasts (CAF) has long been recognized, but the functional significance remains poorly understood. Here, we report the distinction of two CAF subtypes in oral squamous cell carcinoma (OSCC) that have differential tumor-promoting capability, one with a transcriptome and secretome closer to normal fibroblasts (CAF-N) and the other with a more divergent expression pattern (CAF-D). Both subtypes supported higher tumor incidence in nonobese diabetic/severe combined immunodeficient (NOD/SCID) Ilγ2(null) mice and deeper invasion of malignant keratinocytes than normal or dysplasia-associated fibroblasts, but CAF-N was more efficient than CAF-D in enhancing tumor incidence. CAF-N included more intrinsically motile fibroblasts maintained by high autocrine production of hyaluronan. Inhibiting CAF-N migration by blocking hyaluronan synthesis or chain elongation impaired invasion of adjacent OSCC cells, pinpointing fibroblast motility as an essential mechanism in this process. In contrast, CAF-D harbored fewer motile fibroblasts but synthesized higher TGF-ß1 levels. TGF-ß1 did not stimulate CAF-D migration but enhanced invasion and expression of epithelial-mesenchymal transition (EMT) markers in malignant keratinocytes. Inhibiting TGF-ß1 in three-dimensional cultures containing CAF-D impaired keratinocyte invasion, suggesting TGF-ß1-induced EMT mediates CAF-D-induced carcinoma cell invasion. TGF-ß1-pretreated normal fibroblasts also induced invasive properties in transformed oral keratinocytes, indicating that TGF-ß1-synthesizing fibroblasts, as well as hyaluronan-synthesizing fibroblasts, are critical for carcinoma invasion. Taken together, these results discern two subtypes of CAF that promote OSCC cell invasion via different mechanisms.

Antimicrobial susceptibility pattern in nosocomial infections caused by Acinetobacter species in Asir Region, Saudi Arabia.

This study aimed at evaluating the sensitivity of antibiotics towards nosocomial infections caused by Acinetobacter species. The study took place during the period Dec. 2011- Dec. 2012 at Assir Central Hospital in collaboration with the department of microbiology, college of medicine, King Khalid University, Abha. A prospective study involving 150 patients presented with nosocomial infections due to Acinetobacter species detected by bacteriological tests; direct microscopy, culture in blood agar media, fermentation test in MacConkey media and MIC (minimum inhibitory concentration) for antibiotics sensitivity using Muller Hinton media and Chemical test using API 20. A 150 nosocomial infections in this study showed gram-negative coccobacilli, non motile, glucose-negative fermentor and oxidase negative. All isolates showed 100% sensitivity to: Imipramine, Meropenem, Colistin. From the rest of tested antibiotics the higher resistant ones were; Nitrofurantoin 87% and Cefoxitin 85%. The least resistant antibiotics; Imipenem 3% and Ticarcillin 7%. While variable resistance in the rest of tested antimicrobials. A 47 patients (31.3%) have used antibiotics prior to this study. The high rate of usage occurred in elder patients. The frequency of Acinetobacter calcoaceticus baumannii complex multi-drugs resistance ABCMDR is rising including almost all commonly used antibiotics. Only few antibiotics exert 100% sensitivity towards these bacteria.