Mutant profilin1 transgenic mice recapitulate cardinal features of motor neuron disease

The recent identification of profilin1 mutations in 25 familial ALS cases has linked altered function of this cytoskeletonregulating protein to the pathogenesis of motor neuron disease. To investigate the pathological role of mutant profilin1 in motor neuron disease, we generated transgenic lines of mice expressing human profilin1 with a mutation at position 118 (hPFN1G118V). One of the mouse lines expressing high levels of mutant human PFN1 protein in the brain and spinal cord exhibited many key clinical and pathological features consistent with human ALS disease. These include loss of lower (ventral horn) and upper motor neurons (corticospinal motor neurons in layer V), mutant profilin1 aggregation, abnormally ubiquitinated proteins, reduced choline acetyltransferase (ChAT) enzyme expression, fragmented mitochondria, glial cell activation, muscle atrophy, weight loss, and reduced survival. Our investigations of actin dynamics and axonal integrity suggest that mutant PFN1 protein is associated with an abnormally low filamentous/globular (F/G)-actin ratio that may be the underlying cause of severe damage to ventral root axons resulting in a Wallerian-like degeneration. These observations indicate that our novel profilin1 mutant mouse line may provide a new ALS model with the opportunity to gain unique perspectives into mechanisms of neurodegeneration that contribute to ALS pathogenesis

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Lead sorption by carbon nanofibers grown on powdered activated carbon — kinetics and equilibrium

Carbon nano¯bers (CNFs) were synthesized by using a safe and less hazardous method, compared to using °oating catalysts in chemical vapor deposition (CVD) process. This process used C2H2 as carbon source and oil palm kernel shell-based powdered activated carbon (PAC) as cheap solid substrate. Use of nickel (Ni2þ) impregnated PAC as ¯xed substrate for the synthesis of CNF is one of the novelties of the research work accomplished by the authors. The PAC–CNFs porous nanocomposite product was used for the sorption of lead ions (Pb2þ) from synthetic aqueous solution. Kinetics of Pb2þ adsorption and isotherms were investigated by varying initial concentration of lead and contact time. PAC–CNFs were found to remove Pb2þ better at acidic pH of about 5.5. Langmuir and Freundlich isotherms were applied to the sorption equilibrium data to ¯nd the best ¯tted model. Langmuir isotherm model with R2 ¼ 0:965 ¯tted the adsorption data better than the Freundlich isotherm. The kinetic processes of Pb2þ adsorption on CNFs were investigated by applying di®erent kinetic models, namely zero-order, pseudo-¯rst-order and pseudo-second-order. The pseudo-second-order rate equation exhibited the best results with R2 ¼ 0:999, qe ¼ 74:79 (mg/g) and K2 ¼ 0:029 (min . g=mg). The novel nanocomposite product seemed to have the potential to remove Pb2þ ions from aqueous solution

Postauricular pilonidal sinus: a case report with literature review

Introduction: Pilonidal sinus disease (PSD) usually occurs in sacrococcygeal region, with the rare extracoccygeal pilonidal sinus form representing only 2.2% of all pilonidal sinuses. We report a rare postauricular pilonidal sinus with literature review.Methods: Case report.Results: A 25-year-old man, presented with a postauricular nodule with chronic discharge for last three months. On examination, there was a 1 x 1 centimeter firm, tender nodule at the left post auricular area. Under local anaesthesia, the nodule was excited in toto and the wound closed primarily. Histopathological examination confirmed the diagnosis of PSD.Conclusion: The post-auricular region is another rare area of atypical PSD occurring. It may present as a chronic nodule, and excision with primary closure under local anaesthesia may lead to uneventful recovery

DNase I Induces Other Endonucleases in Kidney Tubular Epithelial Cells by Its DNA-Degrading Activity

Endonuclease-mediated DNA fragmentation is both an immediate cause and a result of apoptosis and of all other types of irreversible cell death after injury. It is produced by nine enzymes including DNase I, DNase 2, their homologs, caspase-activated DNase (CAD) and endonuclease G (EndoG). The endonucleases act simultaneously during cell death; however, regulatory links between these enzymes have not been established. We hypothesized that DNase I, the most abundant of endonucleases, may regulate other endonucleases. To test this hypothesis, rat kidney tubular epithelial NRK-52E cells were transfected with the DNase I gene or its inactive mutant in a pECFP expression vector, while control cells were transfected with the empty vector. mRNA expression of all nine endonucleases was studied using real-time RT-PCR; DNA strand breaks in endonuclease genes were determined by PCR and protein expression of the enzymes was measured by Western blotting and quantitative immunocytochemistry. Our data showed that DNase I, but not its inactive mutant, induces all other endonucleases at varying time periods after transfection, causes DNA breaks in endonuclease genes, and elevates protein expression of several endonucleases. This is the first evidence that endonucleases seem to be induced by the DNA-degrading activity of DNase I

Synthesis of carbon nanofibers on impregnated powdered activated carbon as cheap substrate

The catalysis and characterization of carbon nanofibers (CNFs) composite are reported in this work. Carbon nanofibers were produced on oil palm shell powdered activated carbon (PAC), which was impregnated with nickel. Chemical Vapor Deposition (CVD) of C2H2 was used in the presence of hydrogen at ~ 650º C. The flow rates of carbon source and hydrogen were fixed. The CNFs were formed directly on the surface of the impregnated PAC. Variable weight percentage (1, 3, 5, 7 and 9%) of the catalyst salt (Ni+2) were used for the impregnation. However, the best catalysis was observed on the substrate with 3% Ni2+. The product displayed a relatively high surface area, essentially constituted by the external surface. New functional groups were also appeared compared to those in the PAC. Field Emission Scanning Microscopy (FESEM), Transmission Electron Microscopy (TEM), Fourier Transform Infrared (FTIR), BET surface area analysis and Energy Dispersive X-ray analyzer (EDX) were used for the characterization of the new carbon nano product, which was produced through a clean novel process

Modification of powdered activated carbon for the production of Carbon Nanofibers (CNFs)

In the present work, powdered activated carbon (PAC) was modified and used for the production of carbon nanofibers (CNFs). The modification of PAC was done by the impregnation of nickel on the surface of the activated carbon using the wet impregnation method. Variable weight percentage ratios of the catalyst (nickel) ratio were used. The nanofibers were synthesized on the surface of modified PAC by using the Chemical Vapor Deposition (CVD) method at a Temp. of ~ 680º C for one hour in the presence of acetylene as a carbon source. FESEM, TEM, and TGA were used for the characterization of the produ

Efficient lead sorption from wastewater by carbon nanofibers

Wastewater from many industries contains toxic metal ions, which should be removed before water is released into the environment. Many adsorbents have been developed to remove metals, but their efficiency should be improved by, e.g., increasing surface area. Here, we tested the use of carbon nanofibers synthesized on the surface of activated carbon, to remove lead ions (Pb2?). We studied the effect of carbon nanofiber dose, pH, contact time and agitation speed on the sorption capacity. The best conditions were with nanofiber dose of 0.25 g/L, pH of 5.5, contact time of 60 min and agitation speed of 200 rpm. The nanocomposite product was also used for the removal of lead from industrial wastewater. We also found a successful removal of 67 % of lead ions from semiconductor wastewater sample