RESUMEN
Neurodevelopmental disorders (NDDs) are heterogeneous genetic conditions of the central nervous system (CNS). Primary phenotypes of NDDs include epilepsy, loss of developmental skills, abnormal movements, muscle weakness, ocular anomalies, hearing problems, and macro- or microcephaly. NDDs occur due to variants in genes encoding proteins involved in the structure and function of CNS, thus interrupting its normal physiological role. In the study presented here, four consanguineous families (A-D), with members showing neurodevelopmental symptoms, were recruited for clinical and genetic characterization of the phenotypes. Clinical examinations, including Seguin Form Board Test (SFBT), Vineland Social Maturity Scale (VSMS), brain Magnetic Resonance Imaging (MRI), Electroencephalogram (EEG), Electromyography (EMG), Nerve Conduction Velocity (NCV), and Magnetic Resonance Spectroscopy, were employed to characterize the disease phenotypes. Whole exome sequencing (WES) followed by Sanger sequencing was employed to search for the genetic basis of the neurological symptoms observed in four families (A-D). Two of these families (A, B) were of Saudi Arabian origin, and two others (C, D) were of Pakistan origin. Two homozygous missense (KPTN: NM_007059.4:c.301T>G: NP_008990.2; p.(Phe101Val) and MINPP1:NM_001178118.2:c.1202G>A: NP_001171588.1; p.(Arg401Gln)) variants in families A and B, respectively, and two homozygous nonsense (NGLY1:NM_018297.3:c.1534_1541dup: NP_060767.2; p.(Ser515LysfsTer51) and AP4B1:NM_001253852:c.1668G>A: NP_001240781.1; p.(Trp556X)) variants in families C and D, respectively, were identified. Interestingly, additional heterozygous nonsense variant in SON: NM_138927.2: c.5753_5756del: NP_620305.3; p.(Val1918GlufsTer87) and a homozygous variant in FLG (FLG: NM_002016.2:c.7339C>T: NP_002007.1; p.(Arg2447X) were detected in families A and D, respectively. Further, we determined the deleteriousness of each variant through computational approaches. The present study expands the phenotypic and genetic spectrum of NDD-associated genes (KPTN, MINPP1, NGLY1, and AP4B1). Moreover, additional nonsense variants (SON: c.5753_5756del and FLG: c.7339C>T) identified in two families segregating with the phenotype might explain the phenotypic variability and severity in our patients.
Asunto(s)
Trastornos del Neurodesarrollo , Humanos , Arabia Saudita , Fenotipo , Homocigoto , Secuenciación del Exoma , Trastornos del Neurodesarrollo/genética , Mutación/genética , Proteínas de MicrofilamentosRESUMEN
BACKGROUND: The advantages of probiotic administration for acute diarrhoea are mainly shorter duration of symptoms as well as reduced number of stools per day while use of traditional yogurt has similar results. So, this study was conducted to compare the efficacy of yogurt with probiotic in children with acute gastroenteritis. METHODS: This randomized controlled trial was conducted at department of Paediatrics, Children Hospital, Pakistan Institute of Medical Sciences, Islamabad over 1 year. A total of nine hundred and thirty (930) children between 1-5 years of age presenting with acute diarrhoea were enrolled and equally randomized to Group-A (yogurt) and Group-B (lactobacillus rhamnosus) with ORS. The primary outcome was mean frequency of diarrhoea in first 24 hours after initiation of treatment in both the groups. RESULTS: Gender distribution revealed that out of 930 patients, 643 (69.1%) were male and 287 (30.9%) were female while the mean age was 3.14±1.18 years. Mean duration of disease was 4.23±2.02 days. Mean no. of stools in first 24 hours after treatment in Group-A (yogurt) was 3.25±1.64 and 3.29±1.74 in Group-B (probiotics). Student t-test for independent samples was applied and no significant difference was found between the two groups (p=0.713). CONCLUSIONS: Mean frequency of diarrhoea in first 24 hours after treatment with traditional yogurt and commercially available probiotics was not statistically significant in this study.
Asunto(s)
Probióticos , Yogur , Niño , Preescolar , Diarrea/terapia , Femenino , Humanos , Lactante , Masculino , Probióticos/uso terapéutico , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Patients in neonatal intensive care units (NICUs) are at high risk of adverse events. The effects of medical and paramedical education programmes to reduce these have not yet been assessed. METHODS: In this multicentre, stepped-wedge, cluster-randomised controlled trial done in France, we randomly assigned 12 NICUs to three clusters of four units. Eligible neonates were inpatients in a participating unit for at least 2 days, with a postmenstrual age of 42 weeks or less on admission. Each cluster followed a 4-month multifaceted programme including education about root-cause analysis and care bundles. The primary outcome was the rate of adverse events per 1000 patient-days, measured with a retrospective trigger-tool based chart review masked to allocation of randomly selected files. Analyses used mixed-effects Poisson modelling that adjusted for time. This trial is registered with ClinicalTrials.gov, NCT02598609. FINDINGS: Between Nov 23, 2015, and Nov 2, 2017, event rates were analysed for 3454 patients of these 12 NICUs for 65â830 patient-days. The event rate per 1000 patient-days reduced significantly from the control to the intervention period (33·9 vs 22·6; incidence rate ratio 0·67; 95% CI 0·50-0·88; p=0·0048). INTERPRETATION: A multiprofessional safety-promoting programme in NICUs reduced the rate of adverse events and severe and preventable adverse events in highly vulnerable patients. This programme could significantly improve care offered to critically ill neonates. FUNDING: Solidarity and Health Ministry, France.
Asunto(s)
Personal de Salud/educación , Unidades de Cuidado Intensivo Neonatal , Educación Interprofesional , Adulto , Femenino , Humanos , Recién Nacido , MasculinoAsunto(s)
Astenopía/epidemiología , Cefalea/epidemiología , Películas Cinematográficas , Mareo por Movimiento/epidemiología , Adolescente , Adulto , Niño , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pakistán/epidemiología , Estimulación Luminosa , Síndrome , Adulto JovenRESUMEN
Among 831 cases of neonatal bacterial meningitis occurring from 2001 to 2013, Neisseria meningitidis was the third most frequent bacterial species found. All cases occurred only in term neonates and were mainly late onset. Serogroup B accounted for 78% of cases. At diagnosis, 27% of cases had at least one sign of disease severity. All strains were susceptible to cefotaxime, but 12% showed intermediate susceptibility to penicillin G and to aminopenicillin.