Sociodemographic,clinical characteristics,and service utilization of young children diagnosed with autism spectrum disorder at a research center in Saudi Arabia: The road to autism spectrum disorder diagnosis

Objectives:To assess how clinical services are accessed and utilized by young children with suspected autism spectrum disorder (ASD) and identifying factors that prevent the early identification of developmental concerns and diagnosis.Methods:This retrospective study examined the sociodemographic and clinical characteristics of a convenience sample of children diagnosed with ASD at the Center for Autism Research, Riyadh, Saudi Arabia between 2016 and 2018. The characteristics of ASD assessment and intervention service use were examined. Additionally, we examined the association between sociodemographic, clinical, and service use variables with the child’s age at the time of the parent’s initial concern and first ASD diagnosis, and the time from first concern to diagnosis.Results:Out of 127 cases, 67 were diagnosed with ASD (mean: 46.88 months, SD: 18.88, median: 42.00, range, 19-93). Most ASD cases had one previous assessment (n=28, 41.8%). Higher sibling numbers were associated with a later age of first concern (p=0.0278). Applied behavior analysis service utilization was associated with later age of first ASD diagnosis (p=0.0336) and longer time to ASD diagnosis (p=0.0301).Conclusion:Larger sample size is needed to further investigate whether these findings are representative of the national experience. Community-based intervention outcome studies should assess the quality of services being provided.     

Enhancement of Ceramics Based Red-Clay by Bulk and Nano Metal Oxides for Photon Shielding Features

We prepared red clays by introducing different percentages of PbO, Bi₂O₃, and CdO. In order to understand how the introduction of these oxides into red clay influences its attenuation ability, the mass attenuation coefficient of the clays was experimentally measured in a lab using an HPGe detector. The theoretical shielding capability of the material present was obtained using XCOM to verify the accuracy of the experimental results. We found that the experimental and theoretical values agree to a very high degree of precision. The effective atomic number (Z_eff) of pure red clay, and red clay with the three metal oxides was determined. The pure red clay had the lowest Z_eff of the tested samples, which means that introducing any of these three oxides into the clay will greatly enhance its Z_eff, and consequently its attenuation capability. Additionally, the Z_eff for red clay with 10 wt% CdO is lower than the Z_eff of red clay with 10 wt% Bi₂O₃ and PbO. We also prepared red clay using 10 wt% CdO nanoparticles and compared its attenuation ability with the red clay prepared with 10 wt% PbO, Bi₂O₃, and CdO microparticles. We found that the MAC of the red clay with 10 wt% nano-CdO was higher than the MAC of the clay with microparticle samples. Accordingly, nanoparticles could be a useful way to enhance the shielding ability of current radiation shielding materials.     

Clinical and microbiological profile of adult inpatients with community acquired pneumonia in Ilorin,North Central,Nigeria

BackgroundThe optimal management of community acquired pneumonia (CAP) depends on the clinical and microbiological profile in the locality.ObjectivesTo determine the clinical and microbiological profile of patients admitted with CAP in Ilorin, Nigeria.MethodsOne hundred and two consenting consecutively selected patients with clinical and radiologic confirmation of CAP were recruited in 12 months. The socio-demographic, physical examination and laboratory/radiologic parameters were documented in a questionnaire. Microbiological evaluation of their sputum was done and blood samples were taken for complete blood count, culture, serum urea and serological evaluation for atypical bacteria and some viral pathogens.ResultsCAP constituted 5.9% of the total medical admissions during the one-year study period. The mean age of the patients was 49 ± 22 years with the largest frequency in those aged 65 years and above. The commonest symptoms were shortness of breath (96.1%) and cough (94.1%), with a median duration of 3 days from symptom onset to admission. Systemic hypertension was the commonest comorbid illness (25/102; 24.5%). Klebsiella pneumoniae was the predominant pathogen isolated (20/102; 28.1%). The susceptible antibiotics were Imipenem, Ceftazidime and Ceftriaxone. Intra-hospital mortality was 17.6%. CURB – 65 score of ≥ 2 and the presence of complications of CAP were the independent predictors of mortality.ConclusionCAP constitutes a significant disease burden in Ilorin, Nigeria. Typical bacteria accounted for over half of the pathogens isolated from the patients with gram negative agents predominating. This highlights a possible shift in the microbiological profile which could guide empirical treatment.     

Targeting HSF1 disrupts HSP90 chaperone function in chronic lymphocytic leukemia

CLL is a disease characterized by chromosomal deletions, acquired copy number changes and aneuploidy. Recent studies have shown that overexpression of Heat Shock Factor (HSF) 1 in aneuploid tumor cells can overcome deficiencies in heat shock protein (HSP) 90-mediated protein folding and restore protein homeostasis. Interestingly, several independent studies have demonstrated that HSF1 expression and activity also affects the chaperoning of HSP90 kinase clients, although the mechanism underlying this observation is unclear. Here, we determined how HSF1 regulates HSP90 function using CLL as a model system. We report that HSF1 is overexpressed in CLL and treatment with triptolide (a small molecule inhibitor of HSF1) induces apoptosis in cultured and primary CLL B-cells. We demonstrate that knockdown of HSF1 or its inhibition with triptolide results in the reduced association of HSP90 with its kinase co-chaperone cell division cycle 37 (CDC37), leading to the partial depletion of HSP90 client kinases, Bruton''s Tyrosine Kinase (BTK), c-RAF and cyclin-dependent kinase 4 (CDK4). Treatment with triptolide or HSF1 knockdown disrupts the cytosolic complex between HSF1, p97, HSP90 and the HSP90 deacetylase- Histone deacetylase 6 (HDAC6). Consequently, HSF1 inhibition results in HSP90 acetylation and abrogation of its chaperone function. Finally, tail vein injection of Mec-1 cells into Rag2−/−IL2Rγc−/− mice followed by treatment with minnelide (a pro-drug of triptolide), reduced leukemia, increased survival and attenuated HSP90-dependent survival signaling in vivo. In conclusion, our study provides a strong rationale to target HSF1 and test the activity of minnelide against human CLL.     

Reference intervals of biochemical bone turnover markers for Saudi Arabian women: A cross-sectional study

Biochemical bone turnover markers (BTMs) provide important information on the diagnosis, therapy and monitoring of metabolic bone diseases including osteoporosis. One goal of antiresorptive therapy in women is to decrease biochemical BTMs to the lower half of reference intervals for healthy pre-menopausal counterparts, using newly developed automated assays of such markers. The main objectives of the present study were to: (1) establish reference interval values for the following biochemical BTMs: serum osteocalcine (s-OC), bone alkaline phosphatase (s-bone ALP), procollagen type 1 N-terminal propeptide (s-PINP), crosslinked C-terminal telopeptide of Type 1 collagen (s-CTX), tartarate-resistant acid phosphatase isoform 5b (s-TRACP-5b) and urinary: CTX (u-CTX), N-telopeptides of type 1 collagen (u-NTX), pyridinoline (u-PYD) and deoxypyridinoline (u-DPD) in randomly selected Saudi healthy pre-menopausal women; (2) study the changes in biochemical BTMs in relation to age in pre- and post-menopausal women and the factors reported to influence bone turnover and (3) determine the effect of menopausal status on BTMs. A total of 2125 women were studied [including (n = 1557) pre-, and (n = 568) post-menopausal women, respectively, aged 20–79 years]. A total of 765 healthy pre-menopausal women (aged 35–45 years) were used to establish reference intervals for biochemical BTMs. All women studied were medically examined and had their bone mineral density (BMD) values obtained for the lumbar spine (L₁–L₄) and femoral neck according to detailed inclusion criteria. In all women, values of biochemical BTMs, decreased with increasing age up to the age of 45 years, increased steeply among women in their 50s and remained increased in post-menopausal women. Significant increases were evident in all biochemical BTMs in post-menopausal women with > 5 years since menopause with the exception of s-OC, u-DPD, and u-PYD. Using stepwise multiple linear regression analysis, several variables were identified (depending on the BTM) as determinants of BTMs including age, BMI, parity, FSH, LH, PTH, s-Ca, s-Mg, s-PO₄ and 25(OH)D. In the reference intervals group, there are no significant correlations between any of the biochemical BTMs and age of menarche, day of menstrual cycle, physical activity, total daily dietary calcium and caffeine intakes and parity. It is recommended that the age range 35–45 years should be used when establishing biochemical BTMs reference intervals in Saudi Arabian pre-menopausal women.     

Ganoderic acid A/DM-induced NDRG2 over-expression suppresses high-grade meningioma growth

N-myc downstream-regulated gene 2 (NDRG2) is down-regulated in grade-III meningioma [anaplastic meningioma (AM)] and associated with clinically aggressive     

Health needs assessment and determinants of health-seeking behaviour among elderly Nigerians: a house-hold survey

BACKGROUND: In the last decade the number of elderly citizens in Nigeria has increased and their health needs are becoming popularly recognized. A number of factors have also been recognized to determine health care seeking behaviour in these elderly. METHODS: The sample consisted of 756 households that had at least one resident who was aged 60 years and above (35% of 2160 households). Multistage and proportionate sampling techniques were employed to select the study subjects. Structured interview were conducted to elicit information on health needs and determinants of health care seeking behaviour of household members aged 60 years and above. RESULTS: The most frequently reported illnesses were body pain (89.5%), joint pain (86.4%), generalized body weakness and fatigue (81.5%), poor sight (78.2%), fever (71.3%), irritability, anger, and nervous tension (70%), listlessness, depression, and headaches (60%),and decreased mobility (65.8%). More than two-thirds (68.8%) of respondents had never visited health facilities in the last one year even for ordinary medical check-up. Family care/Family consultation was the first choice (44.6%) of treatment for the most frequently reported illnesses irrespective of age group and sex. Less than one-third (28.7%) of the subjects were aware of their health needs. Receiving treatment when sick was the health needs mentioned by the majority (89.4%) of the elderly. Poverty emerged as a major (50.3%) determinant of health care seeking behaviour followed by nature of illness (28.5%). The odds ratio that elderly from poor households will seek health care from unqualified health care practitioners was 0.7 (95% confidence interval (CI) = 0.38-0.67); while the odds ratio that elderly from poor households will seek health care from qualified health care practitioners was 0.8 (95% CI = 0.57-0.89). Self treatment had odds ratio of 1.7 (95% CI = 0.38-0.67). After controlling the household's poverty status, there was still a significance difference (P < 0.05) in age group and gender in terms of health care seeking behaviour. CONCLUSION: Socio-economic indicators and nature of illness were the most pervasive determinants of health care seeking behaviour among the elderly, overriding age and sex, and in terms of health-care expenditure, the nature of illness and quality of service provided ranked the major determinants.     

Loss of miR-200b promotes invasion via activating the Kindlin-2/integrin β1/AKT pathway in esophageal squamous cell carcinoma: An E-cadherin-independent mechanism

Our previous studies have shown that loss of miR-200b enhances the invasiveness of esophageal squamous cell carcinoma (ESCC) cells. However, whether the miR-200-ZEB1/2-E-cadherin regulatory cascade, a master regulator of epithelial-to-mesenchymal transition (EMT), is involved in the regulation of ESCC invasion remains elusive. Here, we show that miR-200b represses ESCC cell invasion in vivo without altering the expression of E-cadherin and vimentin, two surrogate markers of EMT. However, an inverse correlation was observed between the expression levels of miR-200b and ZEB1/2 in both ESCC cell lines (n = 7, P < 0.05) and ESCC tumor samples (n = 88, P < 0.05). Methylation of E-cadherin gene was found to block the regulation of E-cadherin by the miR-200b-ZEB1/2 axis, indicating that an E-cadherin-independent mechanism can mediate the biological function of miR-200b in ESCC. We revealed that miR-200b suppresses the integrin β1-AKT pathway via targeting Kindlin-2 to mitigate ESCC cell invasiveness. In two independent cohorts of ESCC samples (n = 20 and n = 53, respectively), Kindlin-2 expression positively correlated with the activation status of both the integrin signaling pathway and the PI3K-AKT signaling pathway (both P < 0.01). These data highlight that suppression of the Kindlin-2-integrin β1-AKT regulatory axis is an alternative mechanism underlying the tumor suppressor function of miR-200b in ESCC.     

Ear diseases in elderly hospital patients in Nigeria

BACKGROUND: Little information is available about the pattern of ear diseases in the elderly population. Therefore, the present study aims to determine the pattern of ear diseases among elderly Nigerians, so as to provide an objective basis for cost-effective health care planning for the emerging geriatric population. METHODS: A retrospective study of 320 patients aged 60 years or older presenting with ear diseases at the University of Ilorin Teaching Hospital, Ilorin, Nigeria, between January 1996 and December 2001 was carried out. RESULTS: Impacted cerumen was the most common ear disease, occurring in 110 (34.4%) patients of the study population. Chronic suppurative otitis media (CSOM) was the most common infectious disease, affecting 28 (8.8%) patients. Of the 88 patients with hearing loss, 63 (71.6%) had sensorineural, 20 (22.7%) had presbycusis, 1 (1.1%) had conductive, and 4 (4.6%) had mixed hearing loss. CONCLUSION: Our data suggest that impacted cerumen, hearing loss, and infections (notably CSOM), are the common ear diseases among elderly Nigerians.