Association of Vitamin D Status with SARS-CoV-2 Infection or COVID-19 Severity: A Systematic Review and Meta-analysis

This systematic review was conducted to summarize and clarify the evidence on the association between 25-hydroxyvitamin-D [25(OH)D] concentrations and coronavirus disease 2019 (COVID-19) risk and outcomes. PubMed, Scopus, and Web of Science databases and Google Scholar were searched up to 26 November 2020. All retrospective and prospective cohort, cross-sectional, case-control, and randomized controlled trial studies that investigated the relation between 25(OH)D and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and COVID-19 severity were included. Thirty-nine studies were included in the current systematic review. In studies that were adjusted (OR: 1.77; 95% CI: 1.24, 2.53; I²: 44.2%) and nonadjusted for confounders (OR: 1.75; 95% CI: 1.44, 2.13; I²: 33.0%) there was a higher risk of SARS-CoV-2 infection in the vitamin D deficiency (VDD) group. Fifteen studies evaluated associations between VDD and composite severity. In the studies that were adjusted (OR: 2.57; 95% CI: 1.65, 4.01; I² = 0.0%) and nonadjusted for confounders (OR: 10.61; 95% CI: 2.07, 54.23; I² = 90.8%) there was a higher severity in the VDD group. Analysis of studies with crude OR (OR: 2.62; 95% CI: 1.13, 6.05; I²: 47.9%), and adjusted studies that used the Cox survival method (HR: 7.67; 95% CI: 3.92, 15.03; I²: 0.0%) indicated a significant association of VDD with mortality, while in adjusted studies that used logistic regression, no relation was observed (OR: 1.05; 95% CI: 0.63, 1.75; I²: 76.6%). The results of studies that examined relations between VDD and intensive care unit (ICU) admission, pulmonary complications, hospitalization, and inflammation were inconsistent. In conclusion, although studies were heterogeneous in methodological and statistical approach, most of them indicated a significant relation between 25(OH)D and SARS-CoV-2 infection, COVID-19 composite severity, and mortality. With regard to infection, caution should be taken in interpreting the results, due to inherent study limitations. For ICU admission, inflammation, hospitalization, and pulmonary involvement, the evidence is currently inconsistent and insufficient.     

Hb Mizuho [beta 68(E12)Leu----Pro]. Second occurrence identified in a Caucasian child with hemolytic anemia and dense erythrocyte inclusions

Hb Mizuho [beta 68(E12)Leu----Pro] was identified in a child of Italian/Sicilian descent who exhibited severe, transfusion dependent hemolytic anemia which improved following splenectomy. The patient's peripheral blood smear, which prior to splenectomy demonstrated coarse erythrocytic basophilic stippling, showed large, dense erythrocytic hemoglobin inclusions following splenectomy. Whole blood oxygen equilibrium results were consistent with the presence of a hemoglobin component exhibiting increased oxygen affinity with decreased cooperativity. The abnormal beta chain was characterized by high performance liquid chromatography analysis of the isopropanol precipitable hemoglobin fraction.     

Behaviour problems of the mentally retarded.

The behaviour profiles of 176 mentally retarded individuals from two reception centres and nine group homes were assessed. The correlations between behaviour and age, sex, degree of mental retardation, etiology of mental retardation and medical diagnosis were assessed using the Revised Child Behaviour Profile. The severity of behaviour disturbance did not vary with age or medical diagnosis. The moderately retarded subjects presented with more severe behaviour problems, such as aggression, than the severely mentally retarded subjects. The variable most predictive of behavioural problems was etiology of the disorder. Individuals with Down's syndrome had significantly fewer behaviour disturbances and those with autism and pervasive developmental disorder had significantly more behaviour disturbances than other subjects. A psychiatric disorder was found in 10.2% of the sample. The implications of these findings are discussed with respect to public policy.     

Soluble adhesion molecules in acute ischemic stroke

BACKGROUND: Inflammatory adhesion molecules play a key role in the development of ischemic lesions. Elevated plasma concentrations of soluble adhesion molecules are reported in stroke patients, but data are still controversial. Our aim was to explore the potential association of plasma levels of soluble (s) intercellular and vascular cellular adhesion molecules-1 (sICAM-1 and sVCAM-1), sE-selectin and sL-selectin with acute ischemic stroke. METHODS: At our university hospital in Zagreb, Croatia, we prospectively enrolled 67 subjects with acute ischemic stroke, as well as 76 consecutive healthy individuals as controls who were visiting the centre for reasons unrelated to stroke. Serum concentrations of the molecules of interest were determined by means of quantitative sandwich enzyme immunoassay. RESULTS: Mean levels of sICAM-1 (p < 0.001), sVCAM-1 (p < 0.034) and sE-selectin (p < 0.002) were higher in patients than in controls, whereas sL-selectin was lower in patients (p = 0.043). In patients, levels of soluble adhesion molecules were independent of age and sex except for sL-selectin, which was inversely correlated with age (r = -0.260, p = 0.034) and higher in women (p = 0.006) and diabetics (n = 14; p = 0.004). Serum levels did not differ significantly with respect to carotid atherosclerotic disease, smoking status, hypertension or hypercholesterolemia. As well as correlating with each other, concentrations of soluble adhesion molecules in patients correlated with traditional biochemical markers of inflammation: total leukocyte count, erythrocyte sedimentation rate (ESR) and C-reactive protein level. Concentrations of sICAM-1 and high-density lipoprotein-cholesterol and ESR were identified as significant independent predictors/indicators of acute ischemic stroke. CONCLUSIONS: Acute ischemic stroke is associated with elevated plasma levels of sICAM-1, sVCAM-1 and sE-selectin, independent of age, sex and other recognized risk factors for stroke. Decreased levels of sL-selectin are associated with acute stroke. The observed changes in serum concentrations of adhesion molecules indicate inflammatory process occurring during acute cerebral ischemia.     

Croatian population data for the C677T polymorphism in methylenetetrahydrofolate reductase: frequencies in healthy and atherosclerotic study groups

BACKGROUND: The aim of this study was to investigate the frequency of C677T methylenetetrahydrofolate reductase (MTHFR) mutation in healthy Croatian volunteers and in patients with atherosclerosis. METHODS: The C677T MTHFR gene mutation was determined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) in 640 subjects, residents of the Zagreb city or Zagreb surroundings. Control group (n=298) was healthy blood donors. Patients (n=342) were divided into two groups of those with coronary heart disease, CAD (n=247) and those with >60% carotid stenosis, CS (n=95). RESULTS: CC genotype was recorded in 45% of healthy volunteers and 46% of patients (46.3% with CS and 46.2% with CAD). TC genotype was found in 49% of healthy volunteers and 45% of patients (46.3% with CS and 44.9% with CAD). There was no significant difference (p>0.05) from the control group in the genotype or allele frequency either for the overall group of patients with atherosclerosis or for the patient subgroups. CONCLUSION: The preliminary study of MTHFR polymorphism in control subjects and cardiovascular disease/carotid stenosis patients revealed that in Croats there was a low frequency of TT genotype (6% in controls vs. 9% in patients) and T allele (31% for cases and controls). Additionally, our results did not show significantly higher frequency of MTHFR mutation in CAD and CS studied groups.     

Elucidation of the anatomy of a satiety network: Focus on connectivity of the parabrachial nucleus in the adult rat

We hypothesized that brain regions showing neuronal activation after refeeding comprise major nodes in a satiety network, and tested this hypothesis with two sets of experiments. Detailed c‐Fos mapping comparing fasted and refed rats was performed to identify candidate nodes of the satiety network. In addition to well‐known feeding‐related brain regions such as the arcuate, dorsomedial, and paraventricular hypothalamic nuclei, lateral hypothalamic area, parabrachial nucleus (PB), nucleus of the solitary tract and central amygdalar nucleus, other refeeding activated regions were also identified, such as the parastrial and parasubthalamic nuclei. To begin to understand the connectivity of the satiety network, the interconnectivity of PB with other refeeding‐activated neuronal groups was studied following administration of anterograde or retrograde tracers into the PB. After allowing for tracer transport time, the animals were fasted and then refed before sacrifice. Refeeding‐activated neurons that project to the PB were found in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamic area; arcuate, paraventricular, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; parasubthalamic nucleus; central amygdalar nucleus; area postrema; and nucleus of the solitary tract. Axons originating from the PB were observed to closely associate with refeeding‐activated neurons in the agranular insular area; bed nuclei of terminal stria; anterior hypothalamus; paraventricular, arcuate, and dorsomedial hypothalamic nuclei; lateral hypothalamic area; central amygdalar nucleus; parasubthalamic nucleus; ventral posterior thalamic nucleus; area postrema; and nucleus of the solitary tract. These data indicate that the PB has bidirectional connections with most refeeding‐activated neuronal groups, suggesting that short‐loop feedback circuits exist in this satiety network. J. Comp. Neurol. 524:2803–2827, 2016. © 2016 Wiley Periodicals, Inc.     

Synthesis of Hemoglobin Abraham Lincoln (beta 32 leu rarr pro)

Globin chain synthesis was studied in vitrowith reticulocytes from a patient heterozygous for Hb Abraham Lincoln, an unstable beta chain variant. Synthesis of-chains by the reticulocytes exceededtotal -chain synthesis, and a substantialfraction (about 16%) of radioactivityincorporated into globin was recoveredfrom the cells as uncombined subunits.In a time-course study, the ratio of : -chain specific activity was found to increase progressively in a nearly linearmanner, suggesting that a fraction ofnewly synthesized -chains had undergone rapid destruction. The specific activity of the abnormal -chain was nearlythree times that of ^A. The rate of synthesis of the -chain of Hb AbrahamLincoln appeared to be approximately halfthat of the -chain of Hb A.

Submitted on September 13, 1973 Revised on November 1, 1973 Accepted on November 6, 1973