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Mitochondria membrane protein-associated neurodegeneration (MPAN) neurodegenerative disorder is typically associated with biallelic C19orf12 variants. Here we describe a new and review candidate previous monoallelic de novo C19orf12 variants to define loss of function mutations located in the putative non-membrane spanning C19orf12 isoform as the potential basis of monoallelic MPAN.

While molecular studies commonly show lipid abnormalities in monogenic motor neurone diseases, there is no clarity regarding the key functional pathways involved. Rickman et al. review the evidence to propose ‘subcellular lipidome imbalance’ in specific lipid pathways as a common pathological mechanism in these disorders., Motor neuron diseases (MNDs) encompass an extensive and heterogeneous group of upper and/or lower motor neuron degenerative disorders, in which the particular clinical outcomes stem from the specific neuronal component involved in each condition. While mutations in a large number of molecules associated with lipid metabolism are known to be implicated in MNDs, there remains a lack of clarity regarding the key functional pathways involved, and their inter-relationships. This review highlights evidence that defines defects within two specific lipid (cholesterol/oxysterol and phosphatidylethanolamine) biosynthetic cascades as being centrally involved in MND, particularly hereditary spastic paraplegia. We also identify how other MND-associated molecules may impact these cascades, in particular through impaired organellar interfacing, to propose ‘subcellular lipidome imbalance’ as a likely common pathomolecular theme in MND. Further exploration of this mechanism has the potential to identify new therapeutic targets and management strategies for modulation of disease progression in hereditary spastic paraplegias and other MNDs.

Alcohol and drug abuse among college students in the United States concerns both educators and health care providers. Morbidity and mortality from binge drinking, automobile accidents, sexually transmitted diseases, and suicides continue to impact students between 18 and 25 years of age. Those providing health care services to this population have a responsibility to screen for substance abuse. The purpose of this study was to identify college and university student health services currently screening for AODA in students. A survey questionnaire was mailed to 873 student health clinics listed in the directory of the American College Health Association to determine frequency, methods, and outcomes of screening for AODA. Among the 277 respondents, 37% routinely screened for AODA; of those, only 40% had received training in AODA screening. Additional training is needed by student health care personnel; 76% stated that they would attend such training if it were available.

Despite advances in the development of medications to treat alcohol dependence, few medications have been approved by the U.S. Food and Drug Administration. The use of certain anticonvulsant medications has demonstrated potential efficacy in treating alcohol dependence. Previous research suggests that the anticonvulsant levetiracetam may be beneficial in an alcohol-dependent population of very heavy drinkers.In this double-blind, randomized, placebo-controlled clinical trial, 130 alcohol-dependent patients who reported very heavy drinking were recruited across 5 clinical sites. Patients received either levetiracetam extended-release (XR) or placebo and a Brief Behavioral Compliance Enhancement Treatment intervention. Levetiracetam XR was titrated during the first 4 weeks to 2,000 mg/d. This target dose was maintained during weeks 5 through 14 and was tapered during weeks 15 and 16.No significant differences were detected between the levetiracetam XR and placebo groups in either the primary outcomes (percent heavy drinking days and percent subjects with no heavy drinking days) or in other secondary drinking outcomes. Treatment groups did not differ on a number of nondrinking outcomes, including depression, anxiety, mood, and quality of life. The only difference observed was in alcohol-related consequences. The levetiracetam XR treatment group showed significantly fewer consequences than did the placebo group during the maintenance period (p = 0.02). Levetiracetam XR was well tolerated, with fatigue being the only significantly elevated adverse event, compared with placebo (53% vs. 24%, respectively; p = 0.001).This multisite clinical trial showed no efficacy for levetiracetam XR compared with placebo in reducing alcohol consumption in heavy drinking alcohol-dependent patients.

Parasitaemia of Trypanosoma brucei rhodesiense infection in rats peaked on day 5. Afterwards there was a reduction in parasite counts accompanied by anaemia. Prior to the peak, soluble trypanosome antigen was detected in blood of infected rats, but was not found afterwards until the end of the experiment when the parasite counts were again elevated. Onset of reduced parasitaemia with anaemia coincided with appearance of soluble immune complexes, immunoconglutinin and reduced titres of lytic complement. Complexes precipitated from plasma contained parasite antigen. Injection of rats with patent T. b. rhodesiense parasitaemia with antibody against the parasite combined with immunoconglutinin resulted in a prompt reduction in parasite and erythrocyte counts, but did not effect survival of the rats. Injection of the two antibodies did not affect erythrocyte counts of normal rats. The effect was not seen in infected rats injected with parasite antibody alone or with immunoconglutinin alone. From the data it is suggested that antibody against parasite reacted with soluble trypanosomal antigen, forming complexes which fixed complement and became bound to blood cells and trypanosomes and that these cells were immunoconglutinated and removed from the circulation by filter organs of the blood.

Rats experimentally infected with Trypanosoma brucei rhodesiense developed a syndrome characterized by anemia, splenomegaly, and glomerulonephritis. Serologic evaluation revealed that the syndrome was accompanied by the presence of 3 autoantibodies--cold-active hemagglutinin, immunoconglutinin, and antibody to fibrinogen/fibrin products. Fluorescein isothiocyanate conjugated antibody tests showed the presence of fixed complement and fibrinogen on both trypanosomes and erythrocytes. All infected rats died by the ninth day of the infection with 5 animals showing signs of pulmonary involvement and shock. From these observations it is suggested that autoantigens, autoantibodies, and complement may have been causal in this syndrome.

Rats infected with Trypanosoma brucei rhodesiense developed anemia, thrombocytopenia, and hypocomplementemia. Anemia, thrombocytopenia, and sharp reductions in parasitemia were associated with elevated titers of cold-active hemagglutinin, antibody to fibrinogen/fibrin-related products, and immunoconglutinin. Depletion of lytic complement, prolonged partial thromboplastin times, and presence of fibrin monomers in the blood occurred at the time anemia and significant elevations in precipitable immune complexes were observed. Terminally, consumption of immunologic factors coincided with accelerated partial thromboplastin times. At death, convulsions and hemoptysis with labored breathing suggested that the animals died of respiratory failure and that disseminated intravascular coagulation may have occurred. It is suggested that microthrombiosis might have resulted from the immunologic interaction of complex-coated blood cells with immunoconglutinin and contributed to the terminal disease signs.

Antibody to fibrinogen/fibrin related products (Anti-F) was stimulated during the course of Plasmodium chabaudi, Babesia rodhaini, and Trypanosoma lewisi infections in rats. Titers of this au- toantibody remained elevated in serum from rats that had recovered from each of the infections. Column chromatographic studies indicated that Anti-F was a 19S globulin, possibly IgM. During acute infections high titers of Anti-F were associated with elevated titers of cold-active hemagglutinin (CAH) and immu- noconglutinin (IK) and all were associated with anemia and elevated parasitemia. Titers of Anti-F and IK, but not CAH, remained elevated in serum of recovered rats. The presence of Anti-F indicated that the coagulation system had been activated during each infection to release fibrinogen/fibrin-related products (FRP) to serve as antigen(s) for Anti-F. Since IK is antibody to the third component of fixed complement, it could be assumed that complement fixing antigen-antibody complexes were also present during the acute stage of each infection. The possibility that complexes of FRP and Anti-F could have contributed to anemia in each infection is discussed. A syndrome of anemia, splenomegaly, and proliferative glomerulonephritis was shown to be a consequence of infection in rats with Plasmodium chabaudi, Babesia rodhaini, and Trypanosoma lewisi. In each case, the syn- drome was accompanied by elevated titers of cold-activated hemagglutinin (CAH) and an- tibody to the third component of fixed com