Clinical Decision Support for Diabetes Care in the Hospital: A Time for Change Toward Improvement of Management and Outcomes

The increasing prevalence of diabetes permeates hospitals and dysglycemia is associated with poor clinical and economic outcomes. Despite endorsed guidelines, barriers to optimal management and gaps in care prevail. Providers’ limitations on knowledge, attitudes, and decision-making about hospital diabetes management are common. This adds to the complexity of dispersed glucose and insulin dosing data within medical records. This creates a dichotomy as safe and effective care are key objectives of healthcare organizations. This perspective highlights evidence of the benefits of clinical decision support (CDS) in hospital glycemic management. It elaborates on barriers CDS can help resolve, and factors driving its success. CDS represents a resource to individualize care and improve outcomes. It can help overcome a multifactorial problem impacting patients’ lives on a daily basis.     

SARS-CoV-2 Accessory Protein ORF8 Decreases Antibody-Dependent Cellular Cytotoxicity

Viruses use many different strategies to evade host immune responses. In the case of SARS-CoV-2, its Spike mutates rapidly to escape from neutralizing antibodies. In addition to this strategy, ORF8, a small accessory protein encoded by SARS-CoV-2, helps immune evasion by reducing the susceptibility of SARS-CoV-2-infected cells to the cytotoxic CD8+ T cell response. Interestingly, among all accessory proteins, ORF8 is rapidly evolving and a deletion in this protein has been linked to milder disease. Here, we studied the effect of ORF8 on peripheral blood mononuclear cells (PBMC). Specifically, we found that ORF8 can bind monocytes as well as NK cells. Strikingly, ORF8 binds CD16a (FcγRIIIA) with nanomolar affinity and decreases the overall level of CD16 at the surface of monocytes and, to a lesser extent, NK cells. This decrease significantly reduces the capacity of PBMCs and particularly monocytes to mediate antibody-dependent cellular cytotoxicity (ADCC). Overall, our data identifies a new immune-evasion activity used by SARS-CoV-2 to escape humoral responses.     

Folate and Nutrients Involved in the 1-Carbon Cycle in the Pretreatment of Patients for Colorectal Cancer

To assess the ingestion of folate and nutrients involved in the 1-carbon cycle in non-treated patients with colorectal adenocarcinoma in a reference center for oncology in southeastern Brazil. In total, 195 new cases with colorectal adenocarcinoma completed a clinical evaluation questionnaire and a Food Frequency Questionnaire (FFQ). Blood samples from 161 patients were drawn for the assessment of serum folate. A moderate correlation was found between serum concentrations of folate, folate intake and the dietary folate equivalent (DFE) of synthetic supplements. Mulatto or black male patients with a primary educational level had a higher intake of dietary folate. Of patients obtaining folate from the diet alone or from dietary supplements, 11.00% and 0.10%, respectively, had intake below the recommended level. Of the patients using dietary supplements, 35% to 50% showed high levels of folic acid intake. There was a prevalence of inadequacy for vitamins B2, B6 and B12, ranging from 12.10% to 20.18%, while 13.76% to 22.55% of patients were likely to have adequate choline intake. The considerable percentage of patients with folate intake above the recommended levels deserves attention because of the harmful effects that this nutrient may have in the presence of established neoplastic lesions.     

Characterizing a Cohort of α-Thalassemia Couples Collected During Screening for Hemoglobinopathies: 14 Years of an Iranian Experience

Our study aimed to determine the number of couples with normal hemoglobin (Hb) electrophoresis and low-borderline hematological values, which may come up with a clinically critical status in their offspring. The number of couples at risk for severe α-thalassemia (α-thal) needed to be estimated before recommending genetic counseling and prenatal diagnosis (PND). During the past 14 years, from at least 7000 referrals, 754 couples were investigated for α-thal by direct mutation detection methods followed by reverse strip assay and α-globin gene sequencing for inconclusive cases. Detection of silent β-thalassemia (β-thal) mutations was done in suspected cases by complete β-globin gene sequencing. We were able to provide a molecular diagnosis in 87.3% (658/754) of couples. A total of 9.1% (60/658) may have a clinically significant hemoglobinopathy in their offspring. Significant conditions included hydrops fetalis (20.0%; 12/60), certain Hb H (β4) genotypes (78.3%; 47/60) and β-thal intermedia (β-TI) (1.7%; 1/60). The diagnostic flowchart for couples with microcytic hypochromic anemia in countries with a high prevalence of hemoglobinopathies should include α and β gene sequencing. As our results indicate, every nine out of 100 of these couples will face significant hemoglobinopathies and every two out of 100 can carry Hb Bart’s (γ4) hydrops fetalis in their pregnancies. For such cases, PND should be utilized to allow the carrier couples to decide whether or not to abort the fetus.     

Treatment of Neurogenic Voiding Dysfunction: An Update

The neurophysiology of volitional voiding is a poorly understood and constantly evolving field. Some of the most difficult clinical problems in urology arise from structural or neural deviations from this process. These may occur as a result of traumatic injury, congenital defect, or neurological disease. Neurogenic voiding dysfunction is a frequently encountered disorder with multiple etiologies and nonstandardized care. A pervasive complaint in neurogenic voiding dysfunction is detrusor overactivity and resultant urinary incontinence. However, the results of “ideal” initial therapy—catheterization with or without anticholinergics—have been far from satisfactory. This review attempts to go beyond perfunctory measures to explore recent data on anticholinergic therapies, long-term data on botulinum A toxin injections, and applications of neuromodulation.     

Cytidine deamination induced HIV-1 drug resistance

The HIV-1 Vif protein is essential for overcoming the antiviral activity of DNA-editing apolipoprotein B mRNA editing enzyme, catalytic polypeptide 3 (APOBEC3) cytidine deaminases. We show that naturally occurring HIV-1 Vif point mutants with suboptimal anti-APOBEC3G activity induce the appearance of proviruses with lamivudine (3TC) drug resistance-associated mutations before any drug exposure. These mutations, ensuing from cytidine deamination events, were detected in >40% of proviruses with partially defective Vif mutants. Transfer of drug resistance from hypermutated proviruses via recombination allowed for 3TC escape under culture conditions prohibitive for any WT viral growth. These results demonstrate that defective hypermutated genomes can shape the phenotype of the circulating viral population. Partially active Vif alleles resulting in incomplete neutralization of cytoplasmic APOBEC3 molecules are directly responsible for the generation of a highly diverse, yet G-to-A biased, proviral reservoir, which can be exploited by HIV-1 to generate viable and drug-resistant progenies.     

Sleep disruption and quality of life in persons with dementia: A state-of-the-art review

Sleep disruption in persons with dementia is pervasive and contributes to negative health outcomes and decreased quality of life. Using Lawton's framework for quality of life in persons with dementia, the aim of this state-of-the-art review was to synthesize current knowledge on the association between sleep disruption and quality of life in persons with dementia in four domains: physical, social/behavioral, emotional well-being, and cognitive. Based on the final sample of six studies, sleep disruption was negatively associated with all four quality of life domains in persons with dementia. Given the variations in research design, measurement and sample size, conclusions could not be generated on the magnitude of the effects by domain. We do, however, provide recommendations for future research and clinical practice.