Explore the vast range of titles available.

Charcot-Marie-Tooth (CMT) disease is a motor and sensory neuropathy with clinical and genetic heterogeneity. Patients usually present in the first or second decade of life with distal muscle atrophy in the legs, areflexia, foot deformity (mainly pes cavus), and steppage gait. In most cases, hands are also involved as the disease progresses. CMT is the most frequent inherited neuropathy, with a prevalence in Spain of 28 in 100 000.1 Based on electrophysiological studies and histopathologic findings in nerve biopsies, CMT has been subcategorised into two main and distinct neuropathies: (i) demyelinating CMT (CMT1, MIM 118200) associated with reduction in a nerve conduction velocities (NCVs) in all nerves and segmental demyelination and remyelination (\"onion bulbs\"); and (ii) axonal CMT (CMT2, MIM 118220) associated with normal or almost normal NCVs and loss of myelinated axons. Other phenotypes are associated with motor and sensory nerve involvement: Déjérine-Sottas neuropathy (DSN, MIM 145900) is a severe demyelinating neuropathy with onset in infancy, delayed motor milestones, and NCVs less than 10 m/s; congenital hypomyelinating neuropathy (CHN, MIM 605253) is a dysmyelinating neuropathy characterised by infantile hypotonia, distal muscle weakness, and marked reduction of NCVs; hereditary neuropathy with liability to pressure palsies (HNPP, MIM 162500) is a milder sensory and motor neuropathy with periodic episodes of numbness, muscular weakness, and atrophy

Insecticides are widely used in households to control and manage pest populations. Biological insecticides are a more sustainable alternative, but they are often less effective. This study evaluated the effectiveness of avocado seed oil extract with added acetic acid as a bio-insecticide against Aedes aegypti mosquitoes. The researchers used microwave-assisted extraction to obtain the avocado seed oil. Avocado oil and acetic acid were formulated in different volume concentrations: 10%, 30%, 50%, 70%, and 90% (v/v) avocado seed oil extract-infused acetic acid. Assessment of its effectiveness is performed by directly spraying it on Aedes aegypti mosquitoes in a 70x70x70 cm glass cylinder setup and conducting knockdown and mortality tests. The avocado seed oil insecticide showed significant knockdown effectiveness (p= 2.07E-7, α= 0.95) against Aedes aegypti mosquitoes compared to both the positive control (Neem Oil) and negative control (acetic acid). At 1 mL application, all the concentrations have significant differences (p= 0.0044, α= 0.95). The 50% and 90% concentration show the highest efficacy, showing no significant difference (p-value= 0.0527, α= 0.95), the % Knockdown is 25.00% and 20.00%, respectively, while 30% is the lowest at 13.33% within 60 minutes. However, none of the test samples reached 50% knockdown in 60 minutes. At a 3 mL rate, all concentrations resulted in 100% mortality, and the 50% concentration was the fastest in 6 minutes but had no significant difference (p= 0.9746, α= 0.95) with 90% concentration at 10 minutes. All concentrations yield higher efficacy compared to the positive control in both 1 mL and 3 mL rates. In the 1 mL and 3 mL tests, there were no recorded instances of mortality in the pure acetic acid sample. Based on the results, the optimum product among all the formulated concentrations is 50% (v/v) avocado seed oil extract-infused acetic acid having a significant difference (p=2.83E-13, α= 0.95).

We identified three distinct mutations and six mutant alleles in GDAP1 in three families with axonal Charcot-Marie-Tooth (CMT) neuropathy and vocal cord paresis, which were previously linked to the CMT4A locus on chromosome 8q21.1. These results establish the molecular etiology of CMT4A (MIM 214400) and suggest that it may be associated with both axonal and demyelinating phenotypes.

Cerebellar adult onset ataxia is a heterogeneous condition. The aim of this study was to ascertain if there is a heightened autoimmune background in patients with sporadic cerebellar ataxia of unknown origin, and if autoimmunity correlates with a more rapid evolution of the ataxia. We selected patients with sporadic progressive adult onset cerebellar ataxia with a follow-up of >5 years. As controls we included 43 patients with genetically demonstrated hereditary ataxia. All patients were tested for a panel of neuronal (onconeuronal, glutamate-decarboxylase [GAD], IgG/IgA transglutaminase 6 antibodies) and systemic non-neuronal antibodies (including IgG/IgA gliadin and transglutaminase 2, thyroperoxidase, thyroglobulin, antinuclear, striational, smooth muscle, mitochondrial, liver kidney microsomal, and parietal gastric cells antibodies). Correlation between the antibodies and disease progression was studied with Cox regression models and Kaplan–Meier plots. Forty-four patients were included. All patients were negative for onconeuronal or GAD antibodies. There were no significant differences between patients and controls in the prevalence of transglutaminase 6, 2, gliadin, or thyroid antibodies. However, when we studied the panel of systemic non-neuronal autoantibodies as a group, antibodies were more frequent in patients with sporadic ataxia ( p  = 0.018). The presence of one or more systemic non-neuronal antibodies correlated with a faster evolution to stage 2 (loss of independent gait) ( p  = 0.03) and shorter survival ( p  = 0.03) in patients with sporadic ataxia. We conclude that there is probably a heightened autoimmune background in some patients with sporadic cerebellar ataxia of unknown origin. The presence of systemic non-neuronal autoantibodies is a prognostic marker.

Given burdensome side-effects and long latency for efficacy with conventional agents, there is a continued need for generalised myasthenia gravis treatments that are safe and provide consistently sustained, long-term disease control. Nipocalimab, a neonatal Fc receptor blocker, was associated with dose-dependent reductions in total IgG and anti-acetylcholine receptor (AChR) antibodies and clinically meaningful improvements in the Myasthenia Gravis Activities of Daily Living (MG-ADL) scale in patients with generalised myasthenia gravis in a phase 2 study. We aimed to assess the safety and efficacy of nipocalimab in a phase 3 study. Vivacity-MG3 was a phase 3, randomised, double-blind, placebo-controlled, phase 3 study conducted at 81 outpatient centres with expertise in myasthenia gravis in 17 countries in Asia–Pacific, Europe, and North America. Adults (aged ≥18 years) with generalised myasthenia gravis inadequately controlled with standard-of-care therapy (MG-ADL score ≥6) were randomly assigned (1:1) to either nipocalimab (30 mg/kg loading dose then 15 mg/kg every 2 weeks for maintenance dosing) or placebo infusions every 2 weeks, added to standard-of-care therapy in both groups, for 24 weeks. Randomisation was stratified by antibody status, day 1 MG-ADL total score, and region. The sponsor, investigators, clinical raters, and participants were masked to treatment assignment. The primary endpoint was the difference between nipocalimab and placebo based on least-squares mean change from baseline in MG-ADL total score averaged over weeks 22, 23, and 24 in the intention-to-treat population of patients who were antibody-positive (for AChR, anti-muscle-specific tyrosine kinase [MuSK], or anti-low-density lipoprotein receptor-related protein 4 [LRP4]). Adverse events were assessed in patients who received at least one dose of study drug. This study is registered at ClinicalTrials.gov, NCT04951622; the double-blind phase is completed and an open-label extension phase is ongoing. Between July 15, 2021, and Nov 17, 2023, 199 patients were enrolled, and 196 patients received study drug (98 in the nipocalimab group and 98 in the placebo group); of these, 153 (77 in the nipocalimab group and 76 in the placebo group) were antibody-positive. The least-squares mean change in MG-ADL score from baseline to weeks 22, 23, and 24 was –4·70 (SE 0·329) in the nipocalimab group versus –3·25 (0·335) in the placebo group (difference –1·45 [95% CI –2·38 to –0·52]; p=0·0024). The incidence of adverse events was similar between groups (82 [84%] of 98 in both the nipocalimab and placebo groups), including infections (42 [43%] of 98 in the nipocalimab group and placebo group) and headache (14 [14%] of 98 in the nipocalimab group and 17 [17%] of 98 in the placebo group). Serious adverse events were reported for nine (9%) of 98 patients in the nipocalimab group and 14 (14%) of 98 patients in the placebo group, three of which had a fatal outcome (nipocalimab: myasthenic crisis; placebo: cardiac arrest and myocardial infarction). Results from the completed double-blind phase of Vivacity-MG3 support the role of nipocalimab, added to standard-of-care therapies, as a safe treatment for sustained disease control over 6 months for a broad population of patients with generalised myasthenia gravis who are antibody-positive. The ongoing open-label extension phase should provide longer term sustained safety and efficacy data with nipocalimab. Janssen Research & Development, LLC, a Johnson & Johnson company.

Ditaxis heterantha is a plant of the Euphorbiaceae family that grows in semiarid regions of Mexico. It produces yellow pigmented seeds that are used for coloring of foods. The seeds contain about 20% of proteins. Proteins of D. heterantha were extracted and fractionated on the basis of solubility. Three main protein fractions were obtained: glutelins, 488 ± 0.5; albumins, 229 ± 2; and total globulins, 160 ± 1 g/kg. The amino acid profile was evaluated for each fraction and protein isolated, where the protein isolate contains essential amino acids such as Val, Phe, Tyr, and Leu. A calorimetric study showed that globulins and glutelins have a high denaturing temperature between 100 and 106°C, while albumins showed a denaturing temperature at 76°C. The protein isolate and its fractions exhibited functional properties: the isolated protein demonstrated good oil‐holding capacity of 40.7 g/kg. Foam capacity (FC) and foam stability (FS) were observed principally in glutelins and globulins where FC maximum was 330% and the FS was 28 min. The emulsifying capacity was observed in the same fractions of glutelins and globulins, followed by albumins. However, the glutelin fraction in particular was the only fraction that exhibited emulsifying stability at pH 5, 6, and 7. Gelling capacity was observed in albumins and globulins. This study indicated that protein isolated from D. heterantha could be used in food formulations due to its essential amino acid profile. Glutelin could be used as an emulsifying additive. Additionally, glutelin and globulin were stable at temperatures above 100°C; this is an important factor in food industry, principally in heat processes. Differential scanning calorimetry (DSC) thermograms of protein fractions from Ditaxis heterantha.

Little information exists about a causal association between PFO and migraine. Some patients identify Valsalva-provoking activities (VPA) as migraine triggers. Therefore, we speculate about a pathogenic connection. The object of the study is to investigate the prevalence of right-to-left shunt (RLS) in a cohort of patients suffering migraine with aura (MA) and its possible association with migraine attacks triggered by VPA. We investigated the circumstances triggering the migraine attacks, in a consecutive series of 72 MA patients and in a series of migraine without aura age and gender-matched. The presence and extent of RLS was assessed by transcranial Doppler. Massive RLS appeared in 38.9% of MA and in 6.5% of migraine without aura (p<0.001). MA patients identified at least one VPA as headache trigger in 45.8%. A trend was found between these triggering activities and massive RLS, both in MA group OR 2.7 [1.02-7.17] and in all migraine patients OR 2.5 [1.01-6.11]. According to our results, patients with migraine who have larger RLS tend to recognize activities that increase the extent of the shunt as a trigger of their migraine attacks.

A prospective clinical microbiological study of pleural fluid samples was conducted to investigate the etiology of pleural effusions and to evaluate two different methods for transport and culture of these samples. A total of 245 pleural fluid specimens were inoculated into a transport vial, an aerobic and an anaerobic blood culture vial, and a sterile tube. One hundred nine samples were from infectious patients and 128 from noninfectious patients. Gram stain had a sensitivity of 48% and a specificity of 100% as compared to culture. Of the total, 15.5% of the samples were positive for microorganisms, and 60% of the positive samples were nonpurulent pleural fluid. Single-organism growth was found in 23 samples (60.5%). Sixty-three microorganisms were isolated: 25 (39.7%) aerobic, 22 (35%) anaerobic, 13 (20.6%) mycobacteria, and three (4.7%) fungi. Of the 25 positive samples, excluding those samples that grew mycobacteria, nine (36%) were positive exclusively in the blood culture vials. Twelve organisms were isolated, only one of which did not grow in the anaerobic vial. Two (8%) samples were positive by conventional culture only, and 14 (56%) were positive by both methods. The microorganism isolation rate obtained with use of blood culture vials was significantly greater than that obtained with the conventional method of transport and culture. Sixty-three percent of the empyema patients had an associated underlying pathology, pneumonia being the most frequent. In conclusion, for microbiological study of pleural fluid, it seems appropriate to inoculate all samples, including nonpurulent samples, into both a sterile tube and an anaerobic blood culture vial.

Background: Factors influencing length of hospital stay have been poorly analyzed in parapneumonic pleural effusions (PPE). Objectives: The aim of this work is to identify the variables that determine increased hospital stay in patients with infectious pleural effusion (PE). Patients and Methods: We analyzed 112 patients with PE: empyema, complicated parapneumonic and non-complicated parapneumonic. Epidemiologic, biochemical, therapeutic and radiological variables were analyzed. Correlations with hospital stay were studied using the Student’s t test, analysis of variance, Mann-Whitney U-test and linear regression model. Results: Among the 112 patients studied, there were 32 empyema, 50 complicated and 30 non-complicated parapneumonic cases. The median of length stay for all patients was 17 days. Longer hospitalization was required in patients with empyemic PE (p = 0.015), patients with underlying diseases (p = 0.003), those needing pleural drainage (p = 0.005) or decortication (p = 0.043) and those presenting unfavorable radiological outcome after treatment (p = 0.02). Biochemical parameters associated with longer hospital stay were elevated pleural fluid polymorphonuclear elastase (p = 0.001, r = 0.307) and lactate dehydrogenase (p = 0.001, r = 0.312). After linear regression analysis, only underlying disease, pleural drainage and pleural fluid polymorphonuclear elastase values remained in the model, explaining 23.1% of the variability of days of hospitalization. Conclusions: The patients with PPE and empyema who required longer hospitalization were those with purulent fluid, underlying disease, surgical drainage and/or decortication, with unfavorable radiological outcome and higher pleural fluid levels of lactate dehydrogenase and polymorphonuclear elastase.