Recurrent de novo SPTLC2 variant causes childhood-onset amyotrophic lateral sclerosis (ALS) by excess sphingolipid synthesis

BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease of the upper and lower motor neurons with varying ages of onset, progression and pathomechanisms. Monogenic childhood-onset ALS, although rare, forms an important subgroup of ALS. We recently reported specific SPTLC1 variants resulting in sphingolipid overproduction as a cause for juvenile ALS. Here, we report six patients from six independent families with a recurrent, de novo, heterozygous variant in SPTLC2 c.778G>A [p.Glu260Lys] manifesting with juvenile ALS. METHODS: Clinical examination of the patients along with ancillary and genetic testing, followed by biochemical investigation of patients' blood and fibroblasts, was performed. RESULTS: All patients presented with early-childhood-onset progressive weakness, with signs and symptoms of upper and lower motor neuron degeneration in multiple myotomes, without sensory neuropathy. These findings were supported on ancillary testing including nerve conduction studies and electromyography, muscle biopsies and muscle ultrasound studies. Biochemical investigations in plasma and fibroblasts showed elevated levels of ceramides and unrestrained de novo sphingolipid synthesis. Our studies indicate that SPTLC2 variant [c.778G>A, p.Glu260Lys] acts distinctly from hereditary sensory and autonomic neuropathy (HSAN)-causing SPTLC2 variants by causing excess canonical sphingolipid biosynthesis, similar to the recently reported SPTLC1 ALS associated pathogenic variants. Our studies also indicate that serine supplementation, which is a therapeutic in SPTLC1 and SPTCL2-associated HSAN, is expected to exacerbate the excess sphingolipid synthesis in serine palmitoyltransferase (SPT)-associated ALS. CONCLUSIONS: SPTLC2 is the second SPT-associated gene that underlies monogenic, juvenile ALS and further establishes alterations of sphingolipid metabolism in motor neuron disease pathogenesis. Our findings also have important therapeutic implications: serine supplementation must be avoided in SPT-associated ALS, as it is expected to drive pathogenesis further

Contaminación bacteriana y resistencia antibiótica en celulares de médicos del Hospital Vicente Corral Moscoso. Cuenca-2012

Antecedentes: El uso de artículos electrónicos como teléfonos móviles dentro de las unidades de salud, especialmente en hospitales, es muy común. Estos se han difundido sin ninguna restricción ni precaución para desinfectarlos, siendo su uso cada vez más frecuente. Es posible que estos artículos constituyan una fuente de contaminación para infecciones intrahospitalarias. Estudios realizados evidencian contaminaciones bacterianas superiores al 90% en celulares del personal médico, encontrándose bacterias patógenas, como: Estafilococo aureus meticilino sensible y meticilino resistente, Enterococos, Corinebacterium, Klebsiella, Clostridium, Enterobacter, Pseudomona, Acinetobacter, Serratia, Escherichia coli, Proteus. Objetivo: Determinar la contaminación bacteriana y la resistencia antibiótica en los celulares del personal médico del hospital “Vicente Corral Moscoso”. Método: Se realizaron cultivos de la superficie de 276 teléfonos celulares, pertenecientes a médicos tratantes, residentes e internos de medicina del hospital “Vicente Corral Moscoso”. Para la recolección de la muestra se hisopó la superficie del teléfono, se cultivó en agar sangre y en EMB agar, aislando e identificando las bacterias con diferentes pruebas químicas para luego realizar antibiogramas e identificar la susceptibilidad bacteriana con la técnica de Kirby- Bauer. Resultados: El 93,84% de celulares se encontraron contaminados, de estos, los teléfonos de los médicos tratantes mostraban un nivel intenso de contaminación (p=0,001), principalmente por Estafilococo aureus (p=0,022), Estafilococo epidermidis (p=0,012), Enterobacter aerogenes (p=0,019). El personal masculino muestra una contaminación intensa por Enterobacter aerogenes (p=0,024). La resistencia a la Oxacilina en Estafilococos aureus es del 40,7% En las Enterobacterias aisladas se encontró un alto grado de resistencia a cefalosporinas de tercera generación, lo cual sugiere la presencia de cepas BLEE.Background: The use of electronic devices like cell phones in health units, especially in hospitals is very common. These are widely available items without any restriction neither caution to disinfect them and its use is more often. It may be a source of contamination for nosocomial infections. Studies show bacterial contamination above 90% in mobile medical staff found pathogenic bacteria such Staphylococcus aureus sensitive, methicillin-resistant staphylococci, Enterococcus, Corynebacterium, Klebsiella, Clostridium, Enterobacter, Acinetobacter, Serratia, Escherichia coli, Pseudomonas, Proteus. Aims: To determine the bacterial contamination and antibiotic resistance in the cell of "Vicente Corral Moscoso" hospital medical staff. Methods: In this study, a surface culture of 276 cell phones was done, physicians´ property, In senior physicians, medical residents and interns of the “Vicente Corral Moscoso” hospital. We used a swab from the surface to collect the sample and cultured on blood agar and EMB agar, to isolate and identify bacteria with biochemical tests and then susceptibility testing with the Kirby-Bauer technique. Results: The 93.84% of the mobile devices are contaminated. The treating physician’s cells showed a intense level of contamination (p = 0.001), mainly by Staphylococcus aureus (p = 0.022), Staphylococcus epidermidis (p = 0.012), Enterobacter aerogenes (p = 0.019). Male staff shows more intense contamination by Enterobacter aerogenes (p = 0.024). Oxacillin resistance in Staphylococcus aureus is 40.7% in the isolated. Enterobacteriaceae found a high degree of resistance to third generation cephalosporin suggesting the presence of ESBL strains.Cuenc

Contaminación bacteriana y resistencia antibiótica en los celulares del personal de salud médico del Hospital Vicente Corral Moscoso, Cuenca 2011-2012

Antecedentes: El uso de artículos electrónicos como teléfonos móviles dentro de las unidades de salud, especialmente en hospitales, es muy común. Estos se han difundido sin ninguna restricción ni precaución para desinfectarlos, siendo su uso cada vez más frecuente. Es posible que estos artículos constituyan una fuente de contaminación para infecciones intrahospitalarias. Estudios realizados evidencian contaminaciones bacterianas superiores al 90% en celulares del personal médico, encontrándose bacterias patógenas, como: Estafilococo aureus meticilino sensible y meticilino resistente, Enterococos, Corinebacterium, Klebsiella, Clostridium, Enterobacter, Pseudomona, Acinetobacter, Serratia, Escherichia coli, Proteus. Objetivo: Determinar la contaminación bacteriana y la resistencia antibiótica en los celulares del personal médico del hospital Vicente Corral Moscoso . Método: Se realizaron cultivos de la superficie de 276 teléfonos celulares, pertenecientes a médicos tratantes, residentes e internos de medicina del hospital Vicente Corral Moscoso . Para la recolección de la muestra se hisopó la superficie del teléfono, se cultivó en agar sangre y en EMB agar, aislando e identificando las bacterias con diferentes pruebas químicas para luego realizar antibiogramas e identificar la susceptibilidad bacteriana con la técnica de Kirby- Bauer. Resultados: El 93,84% de celulares se encontraron contaminados, de estos, los teléfonos de los médicos tratantes mostraban un nivel intenso de contaminación (p=0,001), principalmente por Estafilococo aureus (p=0,022), Estafilococo epidermidis (p=0,012), Enterobacter aerogenes (p=0,019). El personal masculino muestra una contaminación intensa por Enterobacter aerogenes (p=0,024). La resistencia a la Oxacilina en Estafilococos aureus es del 40,7% En las Enterobacterias aisladas se encontró un alto grado de resistencia a cefalosporinas de tercera generación, lo cual sugiere la presencia de cepas BLEE.auBackground: The use of electronic devices like cell phones in health units, especially in hospitals is very common. These are widely available items without any restriction neither caution to disinfect them and its use is more often. It may be a source of contamination for nosocomial infections. Studies show bacterial contamination above 90% in mobile medical staff found pathogenic bacteria such Staphylococcus aureus sensitive, methicillin-resistant staphylococci, Enterococcus, Corynebacterium, Klebsiella, Clostridium, Enterobacter, Acinetobacter, Serratia, Escherichia coli, Pseudomonas, Proteus. Aims: To determine the bacterial contamination and antibiotic resistance in the cell of "Vicente Corral Moscoso" hospital medical staff. Methods: In this study, a surface culture of 276 cell phones was done, physicians´ property, In senior physicians, medical residents and interns of the “Vicente Corral Moscoso” hospital. We used a swab from the surface to collect the sample and cultured on blood agar and EMB agar, to isolate and identify bacteria with biochemical tests and then susceptibility testing with the Kirby-Bauer technique. Results: The 93.84% of the mobile devices are contaminated. The treating physician’s cells showed a intense level of contamination (p = 0.001), mainly by Staphylococcus aureus (p = 0.022), Staphylococcus epidermidis (p = 0.012), Enterobacter aerogenes (p = 0.019). Male staff shows more intense contamination by Enterobacter aerogenes (p = 0.024). Oxacillin resistance in Staphylococcus aureus is 40.7% in the isolated. Enterobacteriaceae found a high degree of resistance to third generation cephalosporin suggesting the presence of ESBL strains.MédicoCuenc