IL-24 intrinsically regulates Th17 cell pathogenicity in mice

In certain instances, Th17 responses are associated with severe immunopathology. T cell–intrinsic mechanisms that restrict pathogenic effector functions have been described for type 1 and 2 responses but are less well studied for Th17 cells. Here, we report a cell-intrinsic feedback mechanism that controls the pathogenicity of Th17 cells. Th17 cells produce IL-24, which prompts them to secrete IL-10. The IL-10–inducing function of IL-24 is independent of the cell surface receptor of IL-24 on Th17 cells. Rather, IL-24 is recruited to the inner mitochondrial membrane, where it interacts with the NADH dehydrogenase (ubiquinone) 1 α subcomplex subunit 13 (also known as Grim19), a constituent of complex I of the respiratory chain. Together, Grim19 and IL-24 promote the accumulation of STAT3 in the mitochondrial compartment. We propose that IL-24–guided mitochondrial STAT3 constitutes a rheostat to blunt extensive STAT3 deflections in the nucleus, which might then contribute to a robust IL-10 response in Th17 cells and a restriction of immunopathology in experimental autoimmune encephalomyelitis.     

Cerebrovascular responses to somatomotor stimulation in Parkinson’s disease: A multivariate analysis

Parkinson’s disease (PD) is a common neurodegenerative disorder, yet little is known about cerebral haemodynamics in this patient population. Previous studies assessing dynamic cerebral autoregulation (dCA), neurovascular coupling (NVC) and vasomotor reactivity (VMR) have yielded conflicting findings. By using multi-variate modelling, we aimed to determine whether cerebral blood flow (CBF) regulation is impaired in PD patients.55 healthy controls (HC) and 49 PD patients were recruited. PD subjects underwent a second recording following a period of abstinence from their anti-Parkinsonian medication. Continuous bilateral transcranial Doppler in the middle cerebral arteries, beat-to-beat mean arterial blood pressure (MAP; Finapres), heart rate (HR; electrocardiogram), and end-tidal CO₂ (EtCO₂; capnography) were measured. After a 5-min baseline period, a passive motor paradigm comprising 60 s of elbow flexion was performed. Multi-variate modelling quantified the contributions of MAP, ETCO₂ and neural stimulation to changes in CBF velocity (CBFV). dCA, VMR and NVC were quantified to assess the integrity of CBF regulation.Neural stimulation was the dominant input. dCA, NVC and VMR were all found to be impaired in the PD population relative to HC (p < 0.01, p = 0.04, p < 0.01, respectively). Our data suggest PD may be associated with depressed CBF regulation. This warrants further assessment using different neural stimuli.     

Low-risk gestational trophoblastic neoplasia: evaluating the need for initial inpatient treatment during low-dose methotrexate chemotherapy

OBJECTIVE: To evaluate the need for initial inpatient treatment for patients being treated with low-dose intramuscular methotrexate for low-risk gestational trophoblastic neoplasia (GTN). STUDY DESIGN: Clinical notes of all patients treated with low-dose intramuscular methotrexate for low-risk GTN were analyzed and side effects noted. RESULTS: There were no episodes of increased uterine bleeding requiring extra medical intervention. There were 7 cases of chest pain; none required a change from methotrexate chemotherapy. CONCLUSION: Patients being treated with low-dose intramuscular methotrexate for low-risk GTN do not need to be treated routinely in the hospital for their first treatment cycle.     

Investigating COVID-19 Vaccine Impact on the Risk of Hospitalisation through the Analysis of National Surveillance Data Collected in Belgium

The national vaccination campaign against SARS-CoV-2 started in January 2021 in Belgium. In the present study, we aimed to use national hospitalisation surveillance data to investigate the recent evolution of vaccine impact on the risk of COVID-19 hospitalisation. We analysed aggregated data from 27,608 COVID-19 patients hospitalised between October 2021 and February 2022, stratified by age category and vaccination status. For each period, vaccination status, and age group, we estimated risk ratios (RR) corresponding to the ratio between the probability of being hospitalised following SARS-CoV-2 infection if belonging to the vaccinated population and the same probability if belonging to the unvaccinated population. In October 2021, a relatively high RR was estimated for vaccinated people > 75 years old, possibly reflecting waning immunity within this group, which was vaccinated early in 2021 and invited to receive the booster vaccination at that time. In January 2022, a RR increase was observed in all age categories coinciding with the dominance of the Omicron variant. Despite the absence of control for factors like comorbidities, previous infections, or time since the last administered vaccine, we showed that such real-time aggregated data make it possible to approximate trends in vaccine impact over time.     

Socio-cultural factors as correlates of maternal mortality in Edo South Senatorial District,Nigeria

ObjectiveTo investigate the socio-cultural factors that contribute to Maternal Mortality in Edo South Senatorial District.MethodsThe population of the study was made up of 2 157 females of reproductive age and multi-stage random sampling technique was used. The instrument for data collection was a self developed structured and validated questionnaire with a reliability of 0.82. Focus group discussion (FGD) and in-depth interview guide were employed to complement the instrument. Inferential statistics of multiple regressions were also employed to test the hypotheses at 0.05 level of significance.ResultsThe results showed that the socio-cultural variables when taken together contributed positively to maternal mortality [R² = 0.32; CV = 16.5; df = 7). The finding further revealed that six, out of seven of the independent variables in the study significantly contributed to maternal mortality in Edo South Senatorial District. The implications of these findings in maternal and child health care were highlighted.ConclusionsThe study had shown that in addition to medical causes of maternal mortality, there are socio-cultural factors that contribute to women dying during pregnancy, labour and pueperium.     

A practical guide to using insulin

Normally, the level of total body water is maintained by natural elimination and intake. However, several variables can influence the rate of water loss, and if mechanisms that regulate thirst malfunction, intake can be affected as well. The resulting water imbalance can cause excessive or deficient sodium levels. Dr Brown describes the interrelationship between water and sodium concentrations, explains how to calculate a given patient's requirements, and presents a safe approach to the various types of imbalance.