Hereditary sensory neuropathy type I

Hereditary sensory neuropathy type I (HSN I) is a slowly progressive neurological disorder characterised by prominent predominantly distal sensory loss, autonomic disturbances, autosomal dominant inheritance, and juvenile or adulthood disease onset. The exact prevalence is unknown, but is estimated as very low. Disease onset varies between the 2nd and 5th decade of life. The main clinical feature of HSN I is the reduction of sensation sense mainly distributed to the distal parts of the upper and lower limbs. Variable distal muscle weakness and wasting, and chronic skin ulcers are characteristic. Autonomic features (usually sweating disturbances) are invariably observed. Serious and common complications are spontaneous fractures, osteomyelitis and necrosis, as well as neuropathic arthropathy which may even necessitate amputations. Some patients suffer from severe pain attacks. Hypacusis or deafness, or cough and gastrooesophageal reflux have been observed in rare cases. HSN I is a genetically heterogenous condition with three loci and mutations in two genes (SPTLC1 and RAB7) identified so far. Diagnosis is based on the clinical observation and is supported by a family history. Nerve conduction studies confirm a sensory and motor neuropathy predominantly affecting the lower limbs. Radiological studies, including magnetic resonance imaging, are useful when bone infections or necrosis are suspected. Definitive diagnosis is based on the detection of mutations by direct sequencing of the SPTLC1 and RAB7 genes. Correct clinical assessment and genetic confirmation of the diagnosis are important for appropriate genetic counselling and prognosis. Differential diagnosis includes the other hereditary sensory and autonomic neuropathies (HSAN), especially HSAN II, as well as diabetic foot syndrome, alcoholic neuropathy, neuropathies caused by other neurotoxins/drugs, immune mediated neuropathy, amyloidosis, spinal cord diseases, tabes dorsalis, lepra neuropathy, or decaying skin tumours like amelanotic melanoma. Management of HSN I follows the guidelines given for diabetic foot care (removal of pressure to the ulcer and eradication of infection, followed by the use of specific protective footwear) and starts with early and accurate counselling of patients about risk factors for developing foot ulcerations. The disorder is slowly progressive and does not influence life expectancy but is often severely disabling after a long duration of the disease

A Phase 3 Trial of Luspatercept in Patients with Transfusion-Dependent β-Thalassemia

BACKGROUND: Patients with transfusion-dependent β-thalassemia need regular red-cell transfusions. Luspatercept, a recombinant fusion protein that binds to select transforming growth factor β superfamily ligands, may enhance erythroid maturation and reduce the transfusion burden (the total number of red-cell units transfused) in such patients. METHODS: In this randomized, double-blind, phase 3 trial, we assigned, in a 2:1 ratio, adults with transfusion-dependent β-thalassemia to receive best supportive care plus luspatercept (at a dose of 1.00 to 1.25 mg per kilogram of body weight) or placebo for at least 48 weeks. The primary end point was the percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval. Other efficacy end points included reductions in the transfusion burden during any 12-week interval and results of iron studies. RESULTS: A total of 224 patients were assigned to the luspatercept group and 112 to the placebo group. Luspatercept or placebo was administered for a median of approximately 64 weeks in both groups. The percentage of patients who had a reduction in the transfusion burden of at least 33% from baseline during weeks 13 through 24 plus a reduction of at least 2 red-cell units over this 12-week interval was significantly greater in the luspatercept group than in the placebo group (21.4% vs. 4.5%, P<0.001). During any 12-week interval, the percentage of patients who had a reduction in transfusion burden of at least 33% was greater in the luspatercept group than in the placebo group (70.5% vs. 29.5%), as was the percentage of those who had a reduction of at least 50% (40.2% vs. 6.3%). The least-squares mean difference between the groups in serum ferritin levels at week 48 was -348 μg per liter (95% confidence interval, -517 to -179) in favor of luspatercept. Adverse events of transient bone pain, arthralgia, dizziness, hypertension, and hyperuricemia were more common with luspatercept than placebo. CONCLUSIONS: The percentage of patients with transfusion-dependent β-thalassemia who had a reduction in transfusion burden was significantly greater in the luspatercept group than in the placebo group, and few adverse events led to the discontinuation of treatment. (Funded by Celgene and Acceleron Pharma; BELIEVE ClinicalTrials.gov number, NCT02604433; EudraCT number, 2015-003224-31.)

A far-ultraviolet-driven photoevaporation flow observed in a protoplanetary disk.

Most low-mass stars form in stellar clusters that also contain massive stars, which are sources of far-ultraviolet (FUV) radiation. Theoretical models predict that this FUV radiation produces photodissociation regions (PDRs) on the surfaces of protoplanetary disks around low-mass stars, which affects planet formation within the disks. We report James Webb Space Telescope and Atacama Large Millimeter Array observations of a FUV-irradiated protoplanetary disk in the Orion Nebula. Emission lines are detected from the PDR; modeling their kinematics and excitation allowed us to constrain the physical conditions within the gas. We quantified the mass-loss rate induced by the FUV irradiation and found that it is sufficient to remove gas from the disk in less than a million years. This is rapid enough to affect giant planet formation in the disk

Effect of ultrasound on olive oil extraction and optimization of ultrasound-assisted extraction of extra virgin olive oil by response surface methodology (RSM)

In this study, the effects of different extraction parameters including ultrasound time, temperature and malaxation time on olive oil quality were investigated. The extraction variables ultrasound initial temperature (20–50 °C), ultrasound time (2–10 min) and malaxation time (30–50 min) were studied to obtain ideal conditions of ultrasonic treatment on the olive paste for obtaining of a greater yield in the extraction of oil, while maintaining a maximum level of commercial quality. To evaluate the level of commercial quality, absorbance in the UV region, peroxide (PV) and free acidity values (AV), the total chlorophyll, carotenoid, phenol contents, total antioxidant activity and sensory analysis of EVOOs extracted from Edremit cultivar were determined. The optimum conditions were found to be 50 °C, 2 min and 43.23 min for ultrasound initial temperature, sonication time and malaxation time, respectively. This optimal condition gave an extraction yield of 8.25 % and the acidity value of 0.24 mg oleic acid/100 g olive oil. The experimental values obtained under optimal conditions were in agreement with the theoretical values

Traits of intensive livestock systems in Algerian steppe territories

Weather hazards and changing climatic regimes combined with socio-cultural changes are forcing farmers living in Algerian steppe territories to find new strategies to maintain their business, particularly in terms of animal feeding sources. Animal’s nutritional needs in the past used to be met mainly by grazing lands which nowadays cover less than 40% of feeding sources. This study aimed to determine the status of livestock system practices used by breeders in Algerian steppe territories and presents a novel method in identifying intensive systems. Data were obtained from 90 farms through a survey in the province of Tebessa. The farms were divided by their characteristics with a discriminant analysis by zone to know the characteristics of each region. Moreover, a discriminant analysis was performed to select the variables that best differentiated the farms characterised by a different percentage of feed purchased (PFP), which was taken as an index of intensive management. A stepwise regression analysis was also conducted to get predictors variables that mainly influence the percentage of feed purchased and characterise the intensive livestock farms in this area. As a result, livestock systems in steppe territories are up to changing to more intensive forms. These trends appear as solutions for farmers to improve their productivity in the face of various problems. Nevertheless, not to worsen the situation of livestock farming with the orientation towards the intensive system, it is important for farmers to be informed about international policies for practising intensive livestock farming.HIGHLIGHTS The current state of livestock production and practices was identified in the steppe areas. The percentage of purchased feed had greater effects in determining the nature of the livestock systems and identifying intensive systems. The use of modelling techniques in the identification of livestock intensification could be successfully used in the differentiation of livestock systems