C9ORF72 mutations are found in a significant fraction of patients suffering from amyotrophic lateral sclerosis and frontotemporal dementia, yet the function of the C9ORF72 gene product remains poorly understood. Here, we show that mice harboring loss-of-function mutations in the ortholog of C9ORF72 develop splenomegaly, neutrophilia, thrombocytopenia, increased expression of inflammatory cytokines, and severe autoimmunity, ultimately leading to a high mortality rate. Transplantation of mutant bone marrow into wildtype recipients was sufficient to recapitulate the phenotypes observed in the mutant animals, including autoimmunity and premature mortality. Reciprocally, transplantation of wildtype marrow into mutant mice improved their phenotype. We conclude that C9ORF72 serves an important function within the hematopoietic system to restrict inflammation and the development of autoimmunity.

BackgroundMalaria presents a diagnostic challenge in most tropical countries. Microscopy remains the gold standard for diagnosing malaria infections in clinical practice and research. However, microscopy is labour intensive, requires significant skills and time, which causes therapeutic delays. The objective of obtaining result quickly from the examination of blood samples from patients with suspected malaria is now made possible with the introduction of rapid malaria diagnostic tests (RDTs). Several RDTs are available, which are fast, reliable and simple to use and can detect Plasmodium falciparum and non-falciparum infections or both. A study was conducted in tribal areas of central India to measure the overall performance of several RDTs for diagnosis of P. falciparum and non-falciparum infections in comparison with traditional and molecular techniques. Such data will be used to guide procurement decisions of policy makers and programme managers.MethodsFive commercially available RDTs were tested simultaneously in field in parallel with peripheral blood smears in outbreak-affected areas. The evaluation is designed to provide comparative data on the performance of each RDT. In addition, molecular method i.e. polymerase chain reaction (PCR) was also carried out to compare all three methods.ResultsA total of 372 patients with a clinical suspicion of malaria from Bajag Primary Health Centre (PHC) of district Dindori and Satanwada PHC of district Shivpuri attending the field clinics of Regional Medical Research Centre were included in the study. The analysis revealed that the First Response Malaria Antigen pLDH/HRP2 combo test was 94.7% sensitive (95% CI 89.5-97.7) and 69.9% specific (95% CI 63.6-75.6) for P. falciparum. However, for non-falciparum infections (Plasmodium vivax) the test was 84.2% sensitive (95% CI 72.1-92.5) and 96.5% specific (95% CI 93.8-98.2). The Parascreen represented a good alternative. All other RDTs were relatively less sensitive for both P. falciparum and non-falciparum infections.ConclusionsThe results in this study show comparative performance between microscopy, various RDTs and PCR. Despite some inherent limitation in the five RDTs tested, First Response clearly has an advantage over other RDTs. The results suggest that RDTs could play and will play an important role in malaria diagnosis.

Background Digital technology use is nearly ubiquitous among young adults; this use provides both benefits and risks. The risks of technology use include maladaptive technology use or technology addiction. Several conceptualizations of these addictions have emerged, each with its own assessment tools. These conditions include problematic internet use (PIU), internet gaming disorder (IGD), and social media addiction (SMA). These conditions have been associated with health outcomes such as problematic alcohol use, sleep disorders, and mental illness. These maladaptive technology conditions have been most commonly studied in isolation from each other. Objective The aim of this study is to examine PIU, IGD, and SMA together to better inform future research approaches and provider screening practices for young adults. Methods This cross-sectional survey study was conducted using Qualtrics panel-based recruitment and survey hosting. We recruited US young adults aged 18-25 years. The survey assessed PIU, IGD, and SMA. Survey measures also included assessments of problematic alcohol use, sleep, depression, and anxiety. We evaluated the frequency of and overlap in positive screening scores among PIU, IGD, and SMA and modeled each condition using multivariate logistic regression. Finally, we calculated sensitivity and specificity, as well as the positive predictive value and negative predictive value of the screening tools using the most prevalent maladaptive technology type. Results Our 6000 participants had an average age of 21.7 (SD 2.5) years. Of these 6000 participants, 3062 (51.03%) were female, 3431 (57.18%) were Caucasian, 1686 (28.1%) were in a 4-year college program, and 2319 (38.65%) worked full time. The mean PIU score was 3.5 (SD 3.1), and 53.58% (3215/6000) of participants met the criteria for PIU. The mean IGD score was 2.7 (SD 2.6), and 24.33% (1460/6000) of participants met the criteria for IGD. The mean SMA score was 7.5 (SD 5.7), and 3.42% (205/6000) met the criteria for SMA. Across all 3 maladaptive technology use diagnoses, there were varied associations with demographic variables and similar overlap with health outcomes. The sensitivity of PIU screening to detect IGD was 82% and to detect SMA was 93%, whereas the specificity and positive predictive value were much lower (37%-54% specificity; 6%-37% positive predictive value). Conclusions This cross-sectional survey screened a large national sample of adolescents and young adults for PIU, IGD, and SMA to determine prevalence and overlap, demographic associations with each, and associations between these technology-related conditions and health outcomes. There was overlap across PIU, IGD, and SMA in some associated demographic variables and health outcomes. However, the patterns in the associated variables demonstrated unique qualities of each of these conditions.