Molecular Characterization of Egyptian Isolates of Lactobacillus and Bifidobacterium

Abstract: Strains of Lactobacillus and Bifidobacterium were isolated from processed milk collected in Cairo, Egypt. Lactobacilli was isolated on Acetate media (SL) of Rogosa and Mitchell-Weisman. While Bifidobacterium was isolated on DSM medium (Difco Sporulation Medium). The isolates were characterized microscopically, morphologically and by some biochemical tests. DNA was extracted from the specified isolates using (Qiagen, Germany. Cat #51306) and species-specific primers for Lactobacillus and Bifidobacterium were designed to amplify the 16s rDNA gene as a conserved region in the bacterial DNA. Elution of the target band from the gel was performed efficiently and the 16S rDNA region was subjected to sequencing using Sequencer ABI PRISM 3730XL Analyzer. The sequencing data obtained suggested that the two studied isolates were (at the genus level) designated as Lactobacillus and uncultured Bifidobacterium. When the sequencing data was aligned on http://www.ncbi.nlh.nih.gov, it shows 88% homology and expected value of 7e-164 to Lactobacillus kiranofaceins but dendogram tree shows more homology to Lactobacillus plantarum family. While the other sample showed 91% homology and expected value of 3e-113 with Uncultured Bifidobacterium Clone R333 16S rRNA gene. [Hashem S.; H

Efficacy of Semi-Rigid Ureteroscopy and Holmium:YAG Laser Lithotripsy in the Treatment of Ureteric Calculi, a Retrospective Study

Background: Urolithiasis is a common worldwide health problem. Many endosurgical treatments became available for urinary calculi.Objectives: To find out the success clearance and complication rates of ureteric stone treatment using semi-rigid ureteroscopy and Holmium:YAG laser lithotripsy as a day case procedure.Methods: In the period from April 2011 to October 2013, a total of 64 patients who were treated by laser lithotripsy were reviewed retrospectively using Fedail Hospital data. Diagnosis was radiologically confirmed. Semi-rigid ureteroscopy and Holmium:YAG laser lithotripsy was conducted as a day case surgery. Operative details, clearance of stone fragments, failure and complications were analysed. Cases were followed clinically and radiologically after one week and one month.Results: The studied cases were 47 males and 17 females with average age of 47.3 years and ASA I in 52(81.3%). Those who had left ureteric stones were 28(43.8%) patients, only one patient had bilateral stones and 60(93.8%) patients had single stones. The largest stone diameter was 1.9cm. 68.8% had distal ureteric stones, 14.1% had mid third stones, and 17.2% had upper third stones. Most cases 96.9% were operated under spinal anaesthesia with mean operation time 61.2 minutes. Seven patients needed VUJ balloon dilatation to get access to the ureter.20 watt Holmium:YAG laser fibres were used for stone disintegration. 92.2% of cases had uncomplicated clearance, 3.1% minor complications and 4.7% failure of the procedure.100% clearance was confirmed during follow up. Conclusion: Semi-rigid ureteroscopy and Holmium:YAG laser lithotripsy is a safe treatment for ureteric calculi and can be conducted as a day case with high success rate and very low morbidity.Key words: ureteric stone, Semi-rigid ureteroscopy, Holmium:YAG laser lithotripsy

Biallelic Loss-of-Function NDUFA12 Variants Cause a Wide Phenotypic Spectrum from Leigh/Leigh-Like Syndrome to Isolated Optic Atrophy

BACKGROUND: Biallelic loss-of-function NDUFA12 variants have hitherto been linked to mitochondrial complex I deficiency presenting with heterogeneous clinical and radiological features in nine cases only. OBJECTIVES: To fully characterize, both phenotypically and genotypically, NDUFA12-related mitochondrial disease. METHODS: We collected data from cases identified by screening genetic databases of several laboratories worldwide and systematically reviewed the literature. RESULTS: Nine unreported NDUFA12 cases from six pedigrees were identified, with presentation ranging from movement disorder phenotypes (dystonia and/or spasticity) to isolated optic atrophy. MRI showed basal ganglia abnormalities (n = 6), optic atrophy (n = 2), or was unremarkable (n = 1). All carried homozygous truncating NDUFA12 variants, three of which are novel. CONCLUSIONS: Our case series expands phenotype–genotype correlations in NDUFA12-associated mitochondrial disease, providing evidence of intra- and inter-familial clinical heterogeneity for the same variant. It confirms NDUFA12 variants should be included in the diagnostic workup of Leigh/Leigh-like syndromes – particularly with dystonia – as well as isolated optic atrophy

SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission

SLC4A10 is a plasma-membrane bound transporter which utilizes the Na+ gradient to drive cellular HCO3- uptake, thus mediating acid extrusion. In the mammalian brain, SLC4A10 is expressed in principal neurons and interneurons, as well as in epithelial cells of the choroid plexus, the organ regulating the production of cerebrospinal fluid. Using next generation sequencing on samples from five unrelated families encompassing ten affected individuals, we show that biallelic SLC4A10 loss-of-function variants cause a clinically recognizable neurodevelopmental disorder in humans. The cardinal clinical features of the condition include hypotonia in infancy, delayed psychomotor development across all domains and typically severe intellectual impairment. Affected individuals commonly display traits associated with autistic spectrum disorders including anxiety, hyperactivity and stereotyped movements. In two cases isolated episodes of seizures were reported in the first few years of life, and a further affected child displayed bitemporal epileptogenic discharges on EEG without overt clinical seizures. While occipitofrontal circumference was reported to be normal at birth, progressive postnatal microcephaly evolved in 7 out of 10 affected individuals. Neuroradiological features included a relative preservation of brain volume compared to occipitofrontal circumference, characteristic narrow sometimes 'slit-like' lateral ventricles and corpus callosum abnormalities. Slc4a10 -/- mice, deficient for SLC4A10, also display small lateral brain ventricles and mild behavioral abnormalities including delayed habituation and alterations in the 2-object novel object recognition task. Collapsed brain ventricles in both Slc4a10-/- mice and affected individuals suggests an important role of SLC4A10 in the production of the cerebrospinal fluid. However, it is notable that despite diverse roles of the cerebrospinal fluid in the developing and adult brain, the cortex of Slc4a10-/- mice appears grossly intact. Co-staining with synaptic markers revealed that in neurons, SLC4A10 localizes to inhibitory, but not excitatory, presynapses. These findings are supported by our functional studies which show the release of the inhibitory neurotransmitter GABA is compromised in Slc4a10-/- mice, while the release of the excitatory neurotransmitter glutamate is preserved. Manipulation of intracellular pH partially rescues GABA release. Together our studies define a novel characteristic neurodevelopmental disorder associated with biallelic pathogenic variants in SLC4A10 and highlight the importance of further analyses of the consequences of SLC4A10 loss-of-function for brain development, synaptic transmission and network properties

On tail trend detection: modeling relative risk

The climate change dispute is about changes over time of environmental characteristics (such as rainfall). Some people say that a possible change is not so much in the mean but rather in the extreme phenomena (that is, the average rainfall may not change much but heavy storms may become more or less frequent). The paper studies changes over time in the probability that some high threshold is exceeded. The model is such that the threshold does not need to be specified, the results hold for any high threshold. For simplicity a certain linear trend is studied depending on one real parameter. Estimation and testing procedures (is there a trend?) are developed. Simulation results are presented. The method is applied to trends in heavy rainfall at 18 gauging stations across Germany and The Netherlands. A tentative conclusion is that the trend seems to depend on whether or not a station is close to the sea.Comment: 38 page

Mutations in lectin complement pathway genes COLEC11 and MASP1 cause 3MC syndrome

Published version available at https://www.nature.com/articles/ng.757#Ack1This work was supported in part by grants from NEWLIFE (P.L.B., A.D.-F. and C.R.), the Wellcome Trust (P.L.B.), Dubai Harvard Foundation for Medical Research (F.S.A.), the University Hospital of Bordeaux (C.R.), the UK Medical Research Council (A.W.) and EU-FP7 (201804-EUCILIA) (V.H.-H., D.J. and D.P.S.O.). This research was supported by the National Institute for Health Research Biomedical Research Centre at Great Ormond Street Hospital for Children NHS Foundation Trust and University College London (P.L.B.). P.L.B. is a Wellcome Trust Senior Research Fellow

A human ciliopathy reveals essential functions for NEK10 in airway mucociliary clearance

Mucociliary clearance, the physiological process by which mammalian conducting airways expel pathogens and unwanted surface materials from the respiratory tract, depends on the coordinated function of multiple specialized cell types, including basal stem cells, mucus-secreting goblet cells, motile ciliated cells, cystic fibrosis transmembrane conductance regulator (CFTR)-rich ionocytes, and immune cells1,2. Bronchiectasis, a syndrome of pathological airway dilation associated with impaired mucociliary clearance, may occur sporadically or as a consequence of Mendelian inheritance, for example in cystic fibrosis, primary ciliary dyskinesia (PCD), and select immunodeficiencies3. Previous studies have identified mutations that affect ciliary structure and nucleation in PCD4, but the regulation of mucociliary transport remains incompletely understood, and therapeutic targets for its modulation are lacking. Here we identify a bronchiectasis syndrome caused by mutations that inactivate NIMA-related kinase 10 (NEK10), a protein kinase with previously unknown in vivo functions in mammals. Genetically modified primary human airway cultures establish NEK10 as a ciliated-cell-specific kinase whose activity regulates the motile ciliary proteome to promote ciliary length and mucociliary transport but which is dispensable for normal ciliary number, radial structure, and beat frequency. Together, these data identify a novel and likely targetable signaling axis that controls motile ciliary function in humans and has potential implications for other respiratory disorders that are characterized by impaired mucociliary clearance

Characterizing epidemiology of prediabetes, diabetes, and hypertension in Qataris: A cross-sectional study

Objectives To characterize the epidemiologic profiles of prediabetes mellitus (preDM), diabetes mellitus (DM), and hypertension (HTN) in Qataris using the nationally representative 2012 Qatar STEPwise Survey. Methods A secondary data analysis of a cross-sectional survey that included 2,497 Qatari nationals aged 18–64 years. Descriptive and analytical statistical analyses were conducted. Results Prevalence of preDM, DM, and HTN in Qataris aged 18–64 years was 11.9% (95% confidence interval [CI] 9.6%-14.7%), 10.4% (95% CI 8.4%-12.9%), and 32.9% (95% CI 30.4%-35.6%), respectively. Age was the common factor associated with the three conditions. Adjusted analyses showed that unhealthy diet (adjusted odds ratio (aOR) = 1.84, 95% CI 1.01–3.36) was significantly associated with preDM; that physical inactivity (aOR = 1.66, 95% CI 1.12–2.46), central obesity (aOR = 2.08, 95% CI 1.02–4.26), and HTN (aOR = 2.18, 95% CI 1.40–3.38) were significantly associated with DM; and that DM (aOR = 2.07, 95% CI 1.34–3.22) was significantly associated with HTN. Population attributable fraction of preDM associated with unhealthy diet was 7.7%; of DM associated with physical inactivity, central obesity, and HTN, respectively, was 14.9%, 39.8%, and 17.5%; and of HTN associated with DM was 3.0%. Conclusions One in five Qataris is living with either preDM or DM, and one in three is living with HTN, conditions that were found to be primarily driven by lifestyle factors. Prevention, control, and management of these conditions should be a national priority to reduce their disease burden and associated disease sequelae.This publication was made possible by NPRP grant number 10-1208-160017 from the Qatar National Research Fund (a member of Qatar Foundation)