Bilateral Wrist Drop at Presentation in a Child with Spinal Muscular Atrophy Type I

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Clinical Spectrum of Hereditary Spastic Paraplegia in Children : A study of 74 cases

Objectives: The aim of the study was to explore the spectrum of hereditary spastic paraplegia (HSP) in children in Oman. Methods: This retrospective study was carried out between January 1994 and August 2011 on children with delayed development, gait disorders and motor handicaps, with signs of symmetrical pyramidal tract involvement. A detailed perinatal and family history, including the age of onset of symptoms, was recorded. The children were labelled as having either the pure or complicated form of HSP based on the established diagnostic criteria. In families with more than one affected child, parents and all other siblings were also examined. Results: Within the study, 74 children from 31 families were diagnosed with HSP. Parental consanguinity was seen in 91% of cases, with 44 children (59.4%) experiencing onset of the disease under one year of age. Complicated HSP was the most common type, seen in 81.1%. Speech involvement, mental retardation, and epilepsy were the most common associated abnormalities. Nonspecific white matter changes and corpus callosum abnormalities were noted in 24.3% of cases on magnetic resonance imaging. Conclusion: The study described clinical features of 74 children with HSP. Autosomal recessive complicated HSP was seen in 81.1% of cases.

Rituximab Treatment in Myasthaenia Gravis: Report of two paediatric cases

Myasthaenia gravis (MG) is an autoimmune disease involving the postsynaptic receptors in the neuromuscular junction. The condition is characterised by fatigable weakness of the skeletal muscles and is uncommon in children. Acetylcholinesterase inhibitors and immune-modifying medications are usually considered the mainstay of treatment. However, these medications have to be given on a lifelong basis so that patients remain in remission; furthermore, drug-related side-effects can have a major impact on quality of life. We report two paediatric cases who were treated for MG at the Sultan Qaboos University Hospital, Muscat, Oman, in 2007 and 2008, respectively. Rituximab was eventually administered to each patient after their condition failed to improve despite several years of standard treatment with acetylcholinesterase inhibitors and immune-modifying medications. Overall, rituximab resulted in complete remission in one case and significant clinical improvement in the other case. Keywords: Myasthenia Gravis; Rituximab; Children; Cholinergic Receptors; Case Report; Oman

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

Understanding an Extension Technology Acceptance Model of Google Translation: A Multi-Cultural Study in United Arab Emirates

The importance of using Google Translate (GT) has become dominantly more effective. Most researchers, professors, and students rely on its translation as an immediate source of getting the information in different countries all over the world. However, the academic literature fails to acknowledge what factors could contribute to the user's intention to use GT, and consequently fail to discover the effects of using GT. The purpose of this study is to explore GT acceptance in UAE. It is assumed that users' attitude towards GT may vary based on the language used. The variations in languages are unidirectional from the source language (SL) to the target language (TL) and vice versa. The suggested analytical framework is based on an extended TAM model that is proposed by [1]. A quantitative methodology approach was adopted in this study. The hypothesized model is validated empirically using the responses received from a survey of 368 respondents were analyzed using structural equation modeling (SEM-PLS). Results indicated that Perceived Ease of Use, Perceived Usefulness, and Motivation have a significant impact on Behavioral Intention to use GT. In addition, Perceived Usefulness and Motivation significantly influenced Perceived Ease of Use. Furthermore, Perceived Usefulness is in turn influenced by Experience. The findings provide significant theoretical and practical implications for translation researchers, teachers, and MT system developers

Blood Culture Contaminants in a Paediatric Population : Retrospective study from a tertiary hospital in Oman

Objectives: Most children presenting with febrile illness require a blood culture to determine the causative organism as well as its sensitivity to antibiotics. However, false-positive results lead to unnecessary hospitalisations, prescriptions and tests. This study aimed to evaluate the impact of false-positive blood cultures among a paediatric population at a tertiary hospital in Oman. Methods: This retrospective study included all 225 children <13 years old with positive blood cultures who presented to the Sultan Qaboos University Hospital, Muscat, Oman, between July 2011 and December 2013. Blood cultures were reviewed to determine whether they were true-positive or contaminated. Results: A total of 344 positive blood cultures were recorded during the study period, of which 185 (53.8%) were true-positive and 159 (46.2%) were contaminated. Most true-positive isolates (26.5%) were coagulase-negative Staphylococcus spp. (CONS) followed by Escherichia coli (9.7%), while the majority of contaminated isolates were CONS (67.9%) followed by Streptococcus spp. (6.9%). Children with contaminated cultures were significantly younger (P <0.001) while those with true-positive cultures required significantly more frequent hospital admissions, longer hospital stays and more frequent antibiotic prescriptions (P <0.001 each). Chronic illness and mortality was significantly more frequent among those with true-positive cultures (P <0.001 and 0.04, respectively). While white blood cell and absolute neutrophil counts were significantly higher in truepositive cultures (P <0.001 each), there was no significant difference in C-reactive protein (CRP) level (P = 0.791). Conclusion: In this population, CRP level was not an adequate marker to differentiate between true- and falsepositive cultures. A dedicated well-trained phlebotomy team for paediatric patients is essential

2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole is a ligand and shows species-specific partial agonism of the Aryl Hydrocarbon Receptor

2-(4-Amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) and related compounds are a series of anti-cancer candidate pharmaceuticals (Table 1.), that have been shown to activate the AhR. We show that these compounds are high affinity ligands for the rat AhR, but a quantitative assay for their ability to induce CYP1A1 RNA in H4IIEC3 cells, a measure of activation of the AhR, showed a poor relationship between affinity for the AhR and ability to induce CYP1A1 RNA. 5F 203, an agonist with low potency, was able to antagonise the induction of CYP1A1 RNA by TCDD, while IH 445, a potent agonist, did not antagonise the induction of CYP1A1 RNA by TCDD, and Schild analysis confirmed 5F 203 to be a potent antagonist of the induction of CYP1A1 RNA by TCDD in H4IIEC3 cells. In contrast, several benzothiazoles show potent induction of CYP1A1 RNA in human MCF-7 cells, and 5F 203 is unable to detectably antagonise the induction of CYP1A1 RNA in MCF-7 cells, showing a species difference in antagonism. Evaluation of the antiproliferative activity of benzothiazoles showed that the ability to agonise the AhR correlated with growth inhibition both in H4IIEC3 cells for a variety of benzothiazoles, and between H4IIEC3 and MCF-7 cells for 5F 203, suggesting an important role of agonism of the AhR in the anti-proliferative activity of benzothiazoles

Mapping of infection prevention and control education and training in some countries of the World Health Organization’s Eastern Mediterranean Region: current situation and future needs

Abstract Background A strong understanding of infection prevention and control (IPC) procedures and comprehensive training among healthcare workers is essential for effective IPC programs. These elements play a crucial role in breaking the chain of nosocomial infections by preventing the transmission of resistant organisms to patients and staff members. This study mapped the components of IPC education and training across various member states of the World Health Organization (WHO) in the Eastern Mediterranean Region (EMR) at national, academic, and healthcare institutional levels. Methods A self-administered structured online questionnaire based on the WHO “Core Component 3” of IPC programs at the national and acute healthcare facility levels (IPC education and training) was given to national IPC focal persons in each of the WHO’s EMR countries between February and March 2023. Results From 14 of the 22 countries,15 IPC persons participated in the survey. Most countries have scattered nonhomogeneous IPC education programs in human health undergraduate majors without considering it a standalone module. Academic institutions are rarely involved, and elaborate and predefined undergraduate IPC education programs provided by universities are present in 21.4% of the countries. In 71.4% of these countries, postgraduate training targeting IPC professionals is provided by national IPC teams, primarily based on national IPC guidelines developed with the aid of the WHO. Generally, healthcare worker training relies heavily on healthcare facilities in 92.9% of the countries, rather than on a national training program. In 42.9% of the countries, practicing IPC physicians are not necessarily specialists of infectious disease or medical microbiologists and IPC nurses are not required to specialize in IPC. However, nonspecialized IPC professionals are expected to undergo training upon employment and before beginning practice. Nongovernmental organizations such as the WHO play a significant role in IPC education and in supporting national IPC authorities in establishing national IPC guidelines, as it is the case in 78.6% of these countries. Conclusion Clear disparities exist in IPC education and training across different countries in the WHO’s EMR. Establishing a regional scientific network specializing in IPC would help bridge the existing gaps and standardize this education within individual countries and across countries in the region. This region needs to establish IPC certification standards and standardized education curricula

Care and three-year outcomes of children with Benign Epilepsy with Centro-Temporal Spikes in England.

PURPOSE: Benign Epilepsy with Centro-Temporal Spikes (BECTS) is a pediatric epilepsy with typically good seizure control. Although BECTS may increase patients' risk of developing neurological comorbidities, their clinical care and short-term outcomes are poorly quantified. METHODS: We retrospectively assessed adherence to National Institute for Health and Care Excellence (NICE) guidelines relating to specialist referral, electroencephalogram (EEG) conduct and annual review in the care of patients with BECTS, and measured their seizure, neurodevelopmental and learning outcomes at three years post-diagnosis. RESULTS: Across ten centers in England, we identified 124 patients (74 male) diagnosed with BECTS between 2015 and 2017. Patients had a mean age at diagnosis of 8.0 (95% CI = 7.6-8.4) years. 24/95 (25%) patients were seen by a specialist within two weeks of presentation; 59/100 (59%) received an EEG within two weeks of request; and 59/114 (52%) were reviewed annually. At three years post-diagnosis, 32/114 (28%) experienced ongoing seizures; 26/114 (23%) had reported poor school progress; 15/114 (13%) were diagnosed with a neurodevelopmental disorder (six autism spectrum disorder, six attention-deficit/hyperactivity disorder); and 10/114 (8.8%) were diagnosed with a learning difficulty (three processing deficit, three dyslexia). Center-level random effects models estimated neurodevelopmental diagnoses in 9% (95% CI: 2-16%) of patients and learning difficulty diagnoses in 7% (95% CI: 2-12%). CONCLUSIONS: In this multicenter work, we found variable adherence to NICE guidelines in the care of patients with BECTS and identified a notable level of neurological comorbidity. Patients with BECTS may benefit from enhanced cognitive and behavioral assessment and monitoring

PLPHP deficiency:clinical, genetic, biochemical, and mechanistic insights

Biallelic pathogenic variants in PLPBP (formerly called PROSC) have recently been shown to cause a novel form of vitamin B6-dependent epilepsy, the pathophysiological basis of which is poorly understood. When left untreated, the disease can progress to status epilepticus and death in infancy. Here we present 12 previously undescribed patients and six novel pathogenic variants in PLPBP. Suspected clinical diagnoses prior to identification of PLPBP variants included mitochondrial encephalopathy (two patients), folinic acid-responsive epilepsy (one patient) and a movement disorder compatible with AADC deficiency (one patient). The encoded protein, PLPHP is believed to be crucial for B6 homeostasis. We modelled the pathogenicity of the variants and developed a clinical severity scoring system. The most severe phenotypes were associated with variants leading to loss of function of PLPBP or significantly affecting protein stability/PLP-binding. To explore the pathophysiology of this disease further, we developed the first zebrafish model of PLPHP deficiency using CRISPR/Cas9. Our model recapitulates the disease, with plpbp-/- larvae showing behavioural, biochemical, and electrophysiological signs of seizure activity by 10 days post-fertilization and early death by 16 days post-fertilization. Treatment with pyridoxine significantly improved the epileptic phenotype and extended lifespan in plpbp-/- animals. Larvae had disruptions in amino acid metabolism as well as GABA and catecholamine biosynthesis, indicating impairment of PLP-dependent enzymatic activities. Using mass spectrometry, we observed significant B6 vitamer level changes in plpbp-/- zebrafish, patient fibroblasts and PLPHP-deficient HEK293 cells. Additional studies in human cells and yeast provide the first empirical evidence that PLPHP is localized in mitochondria and may play a role in mitochondrial metabolism. These models provide new insights into disease mechanisms and can serve as a platform for drug discovery