A novel pathogenic mutation of the CYP27B1 gene in a patient with vitamin D-dependent rickets type 1: a case report

BACKGROUND: Rickets can occur due to Vitamin D deficiency or defects in its metabolism. Three rare genetic types of rickets with different alterations of genes have been reported, including: Vitamin D dependent rickets type 1, Vitamin D dependent rickets type 2 or also known as Vitamin D resistant rickets and 25 hydroxylase deficiency rickets. Vitamin D dependent rickets type 1 is inherited in an autosomal recessive pattern, and is caused by mutations in the CYP27B1 gene encoding the 1α-hydroxylase enzyme. We report here a new mutation in CYP27B1, which lead to Vitamin D dependent rickets type 1. CASE PRESENTATION: We report on a 13-month-old Arabic Saudi girl with Vitamin D dependent rickets type 1 presented with multiple fractures and classic features of rickets. A whole exome sequencing identified a novel pathogenic missense mutation (CYP27B1:Homozygous c.1510C > T(p.Q504X)) which results in a protein truncating alteration. Both parents are heterozygous carriers of the mutation. Based on data search in Human Gene Mutation Database, 63 CYP27B1 alterations were reported: only 28.6% are protein truncating (5 nonsense, 13 frameshift insertions/deletions, 0 gross deletions), while 61.9% are non-truncating (38 missense, 1 small in-frame insertions/deletion), and 9.5% are possible protein-truncating (5 splice, 1 regulatory). CONCLUSION: The deleterious effect of this alteration, which was the only mutation detected in the CYP27B1 common gene of Vitamin D dependent rickets type 1 in the proband, and its autosomal recessive inheritance fashion, both support a pathogenic nature of this mutation as the cause of Vitamin D dependent rickets type 1

Effects of methylphenidate on attention in Wistar rats treated with the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4)

The aim of this study was to assess the effects of the neurotoxin N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP4) on attention in rats as measured using the 5-choice-serial-reaction-time task (5CSRTT) and to investigate whether methylphenidate has effects on DSP4-treated rats. Methylphenidate is a noradrenaline and dopamine reuptake inhibitor and commonly used in the pharmacological treatment of individuals with attention deficit/hyperactivity disorder (ADHD). Wistar rats were trained in the 5CSRTT and treated with one of three doses of DSP4 or saline. Following the DSP4 treatment rats were injected with three doses of methylphenidate or saline and again tested in the 5CSRTT. The treatment with DSP4 caused a significant decline of performance in the number of correct responses and a decrease in response accuracy. A reduction in activity could also be observed. Whether or not the cognitive impairments are due to attention deficits or changes in explorative behaviour or activity remains to be investigated. The treatment with methylphenidate had no beneficial effect on the rats’ performance regardless of the DSP4 treatment. In the group without DSP4 treatment, methylphenidate led to a reduction in response accuracy and bidirectional effects in regard to parameters related to attention. These findings support the role of noradrenaline in modulating attention and call for further investigations concerning the effects of methylphenidate on attentional processes in rats

Comparative metagenomics approaches to characterize the soil fungal communities of western coastal region, Saudi Arabia

A total of 145007 reads were obtained from pyrosequencing for all the 4 samples. The total count ranged from 11,301,014 (Mecca old road) to 23,503,512 bp (Thuwal). A total of 460 fungal species belonging to 133 genera, 58 families, 33 orders, 13 classes and 4 phyla was identified across the four sites. The most abundant phylum at all four sites was Ascomycota followed by Basidiomycota. Four phyla (Ascomycota-99.31%, Basidiomycota-0.59%, Chytridiomycota-0.04%, Glomeromycota-0.03%) were detected in Khulais. Except for Glomeromycota, all phyla were detected at Mecca old road (Ascomycota-74.26%, Basidiomycota-25.71%, Chytridiomycota-0.01%) and Thuwal (Ascomycota-99.59%, Basidiomycota-0.40%, Chytridiomycota-0.002%); while only Ascomycota-90.98% and Basidiomycota-9.01% were detected in Asfan road. At the class level, Sordariomycetes was predominantly observed at Asfan road-59.88%, Khulais-68.26% and Thuwal-94.84%; while Pezizomycetes was dominant at Mecca old road-56.01%, was absent at Asfan road. Agaricomycetes was present only at Mecca old road-25.73%; while Tremellomycetes-5.77%, Malasseizomycetes-2.13% and Microbotryomycetes-1.10% were found only at Asfan road. The phylogenetic trees revealed that clear genus level differences are visible across all the four sites, with an overall predominance of Thielavia followed by Madurella, Aspergillus, and Gelasinospora. Chaetomium sp., Aspergillus caespitosus and Aspergillus sp. were found in moderate (Mecca old road and Thuwal) to abundant (Asfan road and Khulais) quantities. Thielavia sp., Thielavia hyalocarpa and Madurella sp. are found in moderate quantities at Khulais and Mecca old road, while in abundant levels at Asfan road and Thuwal. Fusarium equisati and F. oxysporum were detected at Thuwal and Khulais. Sordaria araneosa was present at Khulais, while Malasseiza globosa species was detected in moderate quantities across all sites except Khulais

The effects of activation time on the production of fructose and bioethanol from date extract

In this study, fructose and bioethanol were produced from date's extract by fermentation using Saccharomyces cerevisiae, mutant strain ATCC 36858 and wild strain STAR brand, where the latter was activated at different periods: 30 min, 1, 2 and 3 days. Profiles of sugar consumption and bioethanol production using STAR were found to be almost having the same pattern for all activation periods, while fructose was consumed as well as glucose. Enhancement of fructose in sugar can only be obtained at the expense of ethanol. In order to obtain 75 and 90% fructose in sugar, the respective losses in fructose exceeded 39 and 63%. On the other hand, the results demonstrate that S. cerevisiae ATCC 36858 could selectively convert glucose to ethanol and biomass with minimal fructose conversion. A high fructose yield above 91% of the original fructose was obtained with ATCC 36858. In addition, the ethanol yield was found to be 63% of the theoretical.Keywords: Saccharomyces cerevisiae, fructose, glucose, bioethanol, fermentatio

The changing malaria landscape in Aseer region, Kingdom of Saudi Arabia: 2000–2015

Background In 2004, a revised action plan was developed, supported by the World Health Organization, to eliminate malaria from Saudi Arabia by preventing re‑introduction of malaria into regions since declared malaria free, eliminating foci of transmission in the Mecca and Medina areas and a concerted effort of foci surveillance and control, to eliminate malaria from the regions of Jazan and Aseer. This paper provides the context, activities, progress, and possible contributions toward malaria elimination in the Aseer region since 2000, with a more detailed analysis of the spatial location of locally acquired case incidence since 2012. Methods This is a descriptive study of all available Ministry of Health surveillance data and process reports since 2000, with higher spatial resolution analysis of data between 2012 and 2015. Results In 2000, there were 511 cases of Plasmodium falciparumlocally acquired infection. The following 4 years witnessed a dramatic decline in cases to only 18 locally acquired infections reported in 2005. A resurgence in local infections was reported in 2006 (93) and 2007 (165), thereafter (2008–2014) local cases continued to decline to fewer than 40 per year across the region. However, in 2015, a small rise was noted (51). All locally acquired infections were P. falciparum. There has been a constant flow of imported infections into Aseer since 2000, mostly among immigrant labour from Pakistan, India, Sudan, and Yemen. Imported infections have included both Plasmodium vivaxand P. falciparum. The spatial extent of malaria appears to be changing, but there remain two intractable areas Sarat Abeda and Dhran Aljanub, where risks per reporting centre have changed little since 2001, remaining above 0.5 per 10,000 population. Only seven villages contributed 55% of all locally acquired infection since 2012. Discussion Aseer has reached a state of very low incidence of locally acquired infections, despite a constant source of imported infections from outside the country. How many of the local infections are F2 generations from imported infections or how many are a result of residual active transmission between asymptomatic carriers of infections transmitted by pockets of existing Anopheles arabiensispopulations remains unknown. A more detailed investigation of the spatial and temporal patterns of infected hosts, parasites and vectors would help define whether this region has managed to effectively prevent local transmission of new infections</p

Risk associated with malaria infection in Tihama Qahtan, Aseer region, Kingdom of Saudi Arabia: 2006-2007

Introduction: Since 2004, the Kingdom of Saudi Arabia has pursued a policy of malaria elimination. The distribution of malaria at this time was constrained to regions located in the South Western part of the country. The present study aimed to understand the risk of malaria infection and factors associated with these events between March 2006 and August 2007 in one part of Aseer region. Methods: The study was carried out in Tihama Qahtan area in the far southeastern part of Aseer, historically the most malaria endemic area of this region. The area covers 54 villages served by three primary health care centres (Wadi Alhayah, Alfarsha and Albuqaa). Malaria cases were detected using passive case detection (PCD) at the three health centres for 18 months from March 2006, each positive case was investigated using patient and household level enquiries. In addition, four cross-sectional surveys in 12 villages were undertaken using rapid diagnostic tests within the catchments of each health centre coinciding with malaria transmission seasons. Results: Among 1840 individuals examined in the PCD survey, 49 (2.7%) were positive for malaria, most were Plasmodium falciparum cases and one was a P. vivax case. The majority of these infections were likely to have been acquired outside of the area and represent imported cases, including those from the neighboring region of Jazan. Among the 18 locally acquired cases, the majority were adult males who slept outdoors. 3623 individuals were screened during the cross-sectional surveys, 16 (0.44%) were positive and infections only detected during peak, potential transmission periods. Conclusion: There was evidence of local malaria transmission in the Tihama Qahtan area in 2006-2007, however prevalence and incidence of new infections was very low, making the future ambitions of elimination biologically feasible. The constant source of imported infections must be considered in the area’s elimination ambitions, alongside strong behavioural community messages about sleeping outdoors unprotected and travel to malaria endemic areas outside the region

Risk associated with malaria infection in Tihama Qahtan, Aseer region, Kingdom of Saudi Arabia: 2006-2007

Introduction: Since 2004, the Kingdom of Saudi Arabia has pursued a policy of malaria elimination. The distribution of malaria at this time was constrained to regions located in the South Western part of the country. The present study aimed to understand the risk of malaria infection and factors associated with these events between March 2006 and August 2007 in one part of Aseer region. Methods: The study was carried out in Tihama Qahtan area in the far southeastern part of Aseer, historically the most malaria endemic area of this region. The area covers 54 villages served by three primary health care centres (Wadi Alhayah, Alfarsha and Albuqaa). Malaria cases were detected using passive case detection (PCD) at the three health centres for 18 months from March 2006, each positive case was investigated using patient and household level enquiries. In addition, four cross-sectional surveys in 12 villages were undertaken using rapid diagnostic tests within the catchments of each health centre coinciding with malaria transmission seasons. Results: Among 1840 individuals examined in the PCD survey, 49 (2.7%) were positive for malaria, most were Plasmodium falciparum cases and one was a P. vivax case. The majority of these infections were likely to have been acquired outside of the area and represent imported cases, including those from the neighboring region of Jazan. Among the 18 locally acquired cases, the majority were adult males who slept outdoors. 3623 individuals were screened during the cross-sectional surveys, 16 (0.44%) were positive and infections only detected during peak, potential transmission periods. Conclusion: There was evidence of local malaria transmission in the Tihama Qahtan area in 2006-2007, however prevalence and incidence of new infections was very low, making the future ambitions of elimination biologically feasible. The constant source of imported infections must be considered in the area’s elimination ambitions, alongside strong behavioural community messages about sleeping outdoors unprotected and travel to malaria endemic areas outside the region