Symptomatic Erythrocytosis Due to Homozygosity for Hb Luton [HBA2: c.269A>T (or HBA1)] and α-Thalassemia: A Clinical Update

A female proband homozygous for both Hb Luton [α89(FG1)His→Leu (CAC>CTC), HBA2: c.269A>T (or HBA1)], a high oxygen affinity hemoglobin (Hb), and for α⁺-thalassemia (α-thal), (–α^4.2, leftward deletion) was first described in 2012. This is a follow-up report of the same case. At the age of 18, the described patient presented with progressively worsening lethargy, headaches, dizziness, syncope and Raynaud’s phenomenon. Following extensive cardiological and neurological investigation, it was felt that significant erythrocytosis was the most likely cause. Venesection followed by regular exchange transfusions were arranged with marked amelioration in symptomatology. In the vast majority of cases of high oxygen affinity Hbs, venesection is not recommended due to the asymptomatic phenotype and reduced oxygen delivery resulting from venesection. This update describes the evolving phenotype of this unique proband and, to the best of our knowledge, the first use of regular, long-term therapeutic red cell exchange transfusions in a case of high affinity Hb.     

Comparison of success rate and intraocular pressure spikes between selective laser trabeculoplasty and micropulse laser trabeculoplasty in African American and Hispanic patients

AIM: To examine the efficacy and safety of micropulse laser trabeculoplasty (MLT) versus selective laser trabeculoplasty (SLT) in a large cohort of primarily African American and Hispanic patients. METHODS: A single center retrospective comparative cohort review conducted at Cook County Health facilities that included patients with a diagnosis of open angle glaucoma or ocular hypertension who received an SLT or MLT procedure between January 2017 and May 2021. RESULTS: Totally 131 eyes of 99 patients were analyzed. The 77 eyes received SLT and 54 received MLT. Seven out of 77 eyes in the SLT group (9.1%) and 1 out of 54 eyes in the MLT group (1.9%) had an IOP spike (defined as > 5 mm Hg) at either 1h or 1wk after procedure (P=0.05, Chi-squared test with Haldane-Anscombe correction). The procedure failure rate at one year was 50% for SLT and 48% for MLT (P=0.31). CONCLUSION: MLT has a significantly lower incidence of pressure spikes and a similar treatment failure rate at 1-year post-procedure, demonstrating that it is a reasonable alternative compared to SLT.     

“Coming out” as an alcoholic: how former problem drinkers negotiate disclosure of their nondrinking identity

Although communication is critical for former problem drinkers to reject drinks, socialize with others, minimize stigma, and maintain their health and sobriety, recovering alcoholics’ communication has not been examined beyond alcohol self-help groups. Using a Communication Privacy Management framework and in-depth, semistructured interviews, this study examined how former problem drinkers negotiate the disclosure of their nondrinking status. As participants perceived not drinking in the United States as deviant and socially risky, the investigation found participants primarily concealed their nondrinking status in order to fit in. Participants enacted specific communicative behaviors to regulate their privacy boundaries, only disclosing their struggles with alcohol when benefits outweighed costs (e.g., inspiring others, maintaining sobriety, or building relationships). This study offers practical disclosure strategies for former problem drinkers to protect their private information, manage social interactions, and stay sober.     

Associations of Poor Housing with Mental Health Among North Carolina Latino Migrant Farmworkers

This analysis examines the associations of housing conditions with mental health among migrant farmworkers. Data are from a 2010 cross-sectional study conducted in 16 North Carolina counties. Interviews and housing inspections were completed with 371 farmworkers in 186 camps. Mental health measures included depression (Center for Epidemiologic Studies Depression Scale, CES-D), anxiety (Personality Assessment Inventory, PAI), and alcohol misuse (Alcohol Use Disorders Identification Test, AUDIT-C). Housing measures were number of people per sleeping room, perceived security of self and belongings, having a key to dwelling’s door, having bedroom storage, toilet privacy issues, and number of housing regulation violations. Sixty (16.7%) participants had substantial depressive symptoms (CES-D ≥10), 31 (8.8%) had substantial anxiety (PAI ≥27), and 185 (50.1%) had the potential for alcohol misuse (AUDIT-C ≥4). Those with 5+ persons sleeping per room were more likely to have a depression score ≥10 (31.5% vs. 13–14%, P = .01) and an anxiety scores ≥27 (19.6% vs. 5–9%, P = .02). Those who did not feel they or their belongings were secure were more likely to have a depression score ≥10 (19.4% vs. 9.1%, P = .01). Those without a key were more likely to have an anxiety score ≥27 (11.5% vs. 5.1%, P = .04). Those with no bedroom storage were more likely to have a depression score ≥10 (28.9% vs. 14.9%, P = .03). This article suggests links between poor housing and farmworkers’ mental health. These results inform regulations surrounding farmworker housing and inform health care providers on how to prevent and treat poor mental health among migrant farmworkers.     

Qualitative Assessment of a Multi-Scale,Compartmental PBM-DEM Model of a Continuous Twin-Screw Wet Granulation Process

Wet granulation processes play a crucial role in solid oral dosage manufacturing processes. However, they are often designed empirically with poor efficiency. To implement quality-by-design, a more scientific understanding is desired to predict the effects of process and equipment design and material properties on the rate mechanisms governing wet granulation processes. In this study, a multi-dimensional compartmental population balance model of a twin screw granulation process is coupled with discrete element method simulations to evaluate mechanistic rate expressions describing aggregation, breakage, consolidation, and particle flow. Steady-state results are presented for various configurations of the screw elements. The effects of screw element configuration on product size distribution, porosity, and liquid distribution are presented and compared with experimental trends described in literature. Simulated results are consistent with experimental findings, demonstrating the model’s qualitative ability to predict the effects of screw element design and configuration on the particle-scale phenomena and process outcomes.     

Regulation of 3-Hydroxy-3-Methylglutaryl Coenzyme A Reductase Activity in Human Fibroblasts by Lipoproteins

The activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (EC 1.1.1.34), the rate-limiting enzyme of hepatic cholesterol biosynthesis, is suppressed in human fibroblasts cultured in the presence of serum. This enzyme activity increases by more than 10-fold after the removal of serum from the medium. The rise in enzyme activity requires de novo protein synthesis and is not accompanied by changes in the activities of several other cellular enzymes. The factor responsible for the suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase activity in cultured fibroblasts is present in the sera of at least four mammalian species, and in human serum it is found in the low-density lipoproteins. Human high-density lipoproteins, very low-density lipoproteins from chicken egg yolk, and the fraction of human serum containing no lipoproteins do not suppress the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase.     

Detection of periodontal microorganisms in coronary atheromatous plaque specimens of myocardial infarction patients: A systematic review and meta-analysis

BackgroundMicrobial translocation from inflamed periodontal pockets into coronary atheroma via systemic circulation is one of the proposed pathways that links periodontitis and myocardial infarction (MI). The purpose of this systematic review is to determine the reported prevalence of periodontal microorganisms in coronary atheroma and/or aspirated clot samples collected from MI patients with periodontal disease.MethodologyThe “Preferred Reporting Items for Systematic Reviews and Meta-Analyses” (PRISMA) guidelines were followed. Six databases were systematically searched using Medical Subject Headings/Index and Entree terms. After a thorough screening, fourteen publications spanning over ten years (2007–2017) were eligible for this systematic review and meta-analysis.ResultsOut of 14 included studies, 12 reported presence of periodontal bacterial DNA in coronary atherosclerotic plaque specimens. Overall, Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans were the most frequently detected periodontal bacterial species. Meta-analysis revealed that the prevalence of P. gingivalis was significantly higher than A. actinomycetemcomitans in coronary atheromatous plaque samples. Apart from periodontal microbes, DNA from a variety of other microbes e.g. Pseudomonas fluorescens, Streptococcus species, Chlamydia pneumoniae were also recovered from the collected samples.ConclusionConsistent detection of periodontal bacterial DNA in coronary atheroma suggests their systemic dissemination from periodontal sites. It should further be investigated whether they are merely bystanders or induce any structural changes within coronary arterial walls.     

Testing the accelerator hypothesis: body size, beta-cell function, and age at onset of type 1 (autoimmune) diabetes

OBJECTIVE: The "accelerator hypothesis" predicts that fatness is associated with an earlier age at onset of type 1 diabetes. We tested the hypothesis using data from the SEARCH for Diabetes in Youth study. RESEARCH DESIGN AND METHODS: Subjects were 449 youth aged <20 years at diagnosis who had positive results for diabetes antibodies measured 3-12 months after diagnosis (mean 7.6 months). The relationships between age at diagnosis and fatness were examined using BMI as measured at the SEARCH visit and reported birth weight, both expressed as SD scores (SDSs). RESULTS: Univariately, BMI SDS was not related to age at diagnosis. In multiple linear regression, adjusted for potential confounders, a significant interaction was found between BMI SDS and fasting C-peptide (FCP) on onset age (P < 0.0001). This interaction remained unchanged after additionally controlling for number and titers of diabetes antibodies. An inverse association between BMI and age at diagnosis was present only among subjects with FCP levels below the median (<0.5 ng/ml) (regression coefficient -7.9, P = 0.003). A decrease of 1 SDS in birth weight (639 g) was also associated with an approximately 5-month earlier age at diagnosis (P = 0.008), independent of sex, race/ethnicity, current BMI, FCP, and number of diabetes antibodies. CONCLUSIONS: Increasing BMI is associated with younger age at diagnosis of type 1 diabetes only among those U.S. youth with reduced beta-cell function. The intrauterine environment may also be an important determinant of age at onset of type 1 diabetes.