Categorical and anti-categorical approaches to US racial/ethnic groupings: revisiting the National 2009 H1N1 Flu Survey (NHFS)

Intersectionality theory calls for the understanding of race/ethnicity, sex/gender and class as interlinked. Intersectional analysis can contribute to public health both through furthering understanding of power dynamics causing health disparities, and by pointing to heterogeneities within, and overlap between, social groups. The latter places the usefulness of social categories in public health under scrutiny. Drawing on McCall we relate the first approach to categorical and the second to anti-categorical intersectionality. Here, we juxtapose the categorical approach with traditional between-group risk calculations (e.g. odds ratios) and the anti-categorical approach with the statistical concept of discriminatory accuracy (DA), which is routinely used to evaluate disease markers in epidemiology. To demonstrate the salience of this distinction, we use the example of racial/ethnic identification and its value for predicting influenza vaccine uptake compared to other conceivable ways of organizing attention to social differentiation. We analyzed data on 56,434 adults who responded to the NHFS. We performed logistic regressions to estimate odds ratios and computed the area under the receiver operating characteristic curve (AU-ROC) to measure DA. Above age, the most informative variables were education and household poverty status, with race/ethnicity providing minor additional information. Our results show that the practical value of standard racial/ethnic categories for making inferences about vaccination status is questionable, because of the high degree of outcome variability within, and overlap between, categories. We argue that, reminiscent of potential tension between categorical and anti-categorical perspectives, between-group risk should be placed and understood in relationship to measures of DA, to avoid the lure of misguided individual-level interventions.     

Management of dentoalveolar injuries in children: a case report

Children aged 6-15 years old experience more injuries to their teeth and the injuries sustained are more serious as evidenced by a higher percentage of luxations, avulsions, fractures and dislocations. The mandible is the most frequently fractured facial bone and mandibular alveolar injuries have been reported to range between 8.1-50.6%. Those with mandibular or midface fractures have a higher incidence of associated chest, extremity, abdomen and cervical spine injuries. The growing patient with facial injuries presents the clinician with a series of thought-provoking circumstances. Dentoalveolar and mandibular injuries are especially important to understand because of the potential complications related to tooth eruption, alveolar development, occlusion and facial growth. However, the principles involved in the treatment for children need to be modified by certain anatomical, physiological and psychological factors specifically related to childhood. This case report documents the trauma, management and follow-up care of an 11-year-old boy who sustained undisplaced infraorbital, nasal fractures and mandibular dentoalveolar fracture along with other associated injuries of the extremities.     

MYD88 L265P mutation in intraocular lymphoma: A potential diagnostic marker

Purpose:Vitreoretinal lymphoma (VRL) is the most common intraocular lymphoma (IOL). This can be either primary or secondary to the central nervous system lymphoma. The diagnosis of primary intraocular lymphoma (PIOL) currently relies on clinical diagnosis and cytological analysis of the vitreous or subretinal biopsy. Although most cases are diagnosed without much issue, the limited amount of vitreous fluid, subjectivity in cytological reporting, and special expertise in ocular pathology make the diagnosis challenging. MYD88 L265P mutation has been implicated to have diagnostic utility in PIOL. In this study, we screened consecutive vitreous biopsies for the presence of MYD88 L265P mutation to understand its diagnostic utility compared to conventional cytological analysis.Methods:Cytological analysis and MYD88 L265P mutation by PCR-based sequencing and restriction fragment length polymorphism (RFLP) were carried out on consecutive vitreous and subretinal biopsies collected from 21 patients. The diagnostic utility of the cytology and MYD88 L265P mutation analysis were compared.Results:Out of the 21 patients, 15 had clinical suspicion of having PIOL. Out of these suspected cases of PIOL, nine were confirmed on follow-up, while six were diagnosed as other intraocular pathologies. Diagnostic utility of MYD88 L265P mutation analysis revealed a sensitivity of 88.9%, specificity of 91.6%, positive and negative predictive value of 88.9% and 91.7%, respectively. Diagnostic accuracy of 90.5% was achieved with the mutation analysis that shows the superiority of MYD88 in both ruling in and ruling out PIOL. The diagnostic utility of MYD88 L265P mutation was superior to conventional cytological analysis.Conclusion:The analysis of MYD88 L265P mutation is reliable and efficient in the diagnosis of PIOL.     

Rosmarinic acid attenuates hepatic steatosis by modulating ER stress and autophagy in oleic acid-induced HepG2 cells

Non-alcoholic fatty acid disease (NAFLD) has become an emerging entity of liver disorders worldwide. Oxidative stress and deranged autophagy-induced endoplasmic reticulum (ER) stress has recently been recognized as one of the prime factors involved in the pathological mechanism underlying NAFLD and progressive non-alcoholic steato-hepatitis (NASH). Epidemiological and experimental data reveal the potency of dietary polyphenols in averting NAFLD. In this line, to analyse and address the underlying pathogenic mechanisms, in the present study, oleic acid-induced HepG2 cells were treated with rosmarinic acid (RA), a dietary polyphenol with well-established cytoprotective properties. Treatment with rosmarinic acid (20 μg) was found to potently counter the elevated levels of total cholesterol (TC) and triglycerides (TG). Additionally, exposure of oleic acid-induced HepG2 cells to rosmarinic acid showed reduced levels of ROS and increased activity of enzymic and non-enzymic antioxidants. The steatotic HepG2 cells presented a pronounced increase in the expression of key ER stress markers such as p-PERK, p-IRE-1, ATF-6, p-eIF-α and CHOP, which was considerably reduced upon treatment with rosmarinic acid. Moreover, exposure to rosmarinic acid altered the deranged autophagic mechanism in oleic acid-induced HepG2 cells, which was observed via the protein expression of Beclin 1, LC31, ATG5 and ATG7. This study demonstrates that rosmarinic acid abrogates NAFLD via diminishing ER stress by nullifying oxidative stress and restoring deranged autophagy and can be used as a potent adjunct in the treatment of NAFLD, thus illustrating the valuable application of polyphenols in combating NAFLD.

Non-alcoholic fatty acid disease (NAFLD) has become an emerging entity of liver disorders worldwide.     

Heart failure in people with type 2 diabetes vs. those without diabetes: A retrospective observational study from South India

Background and aimDespite diabetes being an independent risk for HF, only some DM patients develop HF and hence our aim was to compare the clinical features of DM with and without HF and non-DM with and without HF.MethodsA retrospective observational study was conducted among 397 individuals who visited two tertiary care centres. They were classified into 4 groups – DM with HF(DM-HF), DM without HF, non-DM with HF(non-DM-HF) and non-DM without HF. We assessed and compared the clinical profile of DM with HF vs. DM without HF and non-DM with HF groups respectively.ResultsThe parameters such as age, BMI, BP, eGFR showed significant difference between the groups. People with DM-HF were older compared to DM without HF group(58.9 ± 9.2vs.49.5 ± 9.3; p < 0.001). An increasing trend was observed in HF prevalence with increasing duration of DM among the DM-HF group. DM-HF showed a higher prevalence of hypertension and coronary artery disease(CAD) by history than DM without HF group. DM-HF group(91.2%) had HF with preserved left ventricular ejection fraction(HFpEF) whereas a high proportion(43.5%) of non-DM-HF group had HF with reduced LV ejection fraction(HFrEF).ConclusionsThe DM-HF group differed from other groups significantly in age, diabetes duration, HbA1c level, prevalence of hypertension, CAD and HFpEF.     

Unusual immunophenotype of CD8+ T cells in familial hemophagocytic lymphohistiocytosis

Familial hemophagocytic lymphohistiocytosis (FHL) is an inherited, fatal disorder of infancy. We report here a 17-day-old female infant who presented with high fever, hepatosplenomegaly, hypertriglyceridemia, hypofibrinogenemia, thrombocytopenia, and liver failure. Leukocytosis was detected with circulating "atypical" lymphoid cells. Flow cytometric studies revealed expanded subpopulations of CD8+ T cells with unusual immunophenotypic features, including a subset that lacked CD5 expression. A liver biopsy showed hemophagocytic lymphohistiocytosis with exuberant infiltrates of CD8+ T cells that lacked perforin. Mutational studies revealed a 666C-->A (H222Q) missense mutation in the perforin gene. T-cell receptor studies on flow-sorted T-cell subpopulations revealed no evidence of monoclonality. Analysis of T-cell receptor excision circle levels indicated long proliferative history in the aberrant CD8+ T-cell subsets. This case provides an instructive example of uncontrolled reactive proliferation of CD8+ T cells in FHL, resulting in atypical morphology and unusual immunophenotypic features that might suggest malignancy in other clinical settings.     

Comparison of diltiazem at two dose levels with propranolol for treatment of stable angina pectoris

Two dose levels of diltiazem with propranolol were compared in the management of chronic stable angina. Two groups of patients were treated for alternate periods of 4 weeks with each drug in a double-blind crossover with computer-assisted maximal treadmill tests and ambulatory ST-segment monitoring for evaluation of efficacy and safety. In 12 patients who received diltiazem, 180 mg/day, the time to development of angina increased from 5.9 +/- 0.7 minutes (+/- standard error of the mean) during placebo treatment to 8.3 +/- 0.8 minutes during diltiazem treatment and to 9.2 +/- 0.8 minutes with propranolol, 240 mg/day. Three patients became angina-free when they were treated with both drugs. Among 12 patients who received diltiazem, 360 mg/day, 1 patient became angina-free during treatment with both drugs and 1 became angina-free with diltiazem only. The mean exercise time increased from 5.8 +/- 0.7 minutes with placebo to 8.6 +/- 1.0 minutes with diltiazem, 360 mg/day, and to 8.2 +/- 0.6 minutes with propranolol, 240 mg/day. Analysis of variance showed no difference in efficacy between the 2 doses of diltiazem or between the 2 drugs. Ambulatory heart rate was reduced both during the day and at night with both drugs and significantly more with propranolol than with diltiazem treatment. Except for 1 patient in whom a rash developed when given diltiazem, 180 mg/day, and another who had both a rash and first-degree heart block with diltiazem, 360 mg/day, both drugs were well tolerated. Thus, diltiazem in a daily dose of 180 or 360 mg/day is as effective as propranolol for the treatment of chronic stable angina.     

Association of TM4SF4 with the Human Thiamine Transporter-2 in Intestinal Epithelial Cells

Background

The human thiamine transporter-2 (hTHTR-2) is involved in the intestinal absorption of thiamine. Recent studies with membrane transporters of other nutrients/substrates have shown that they have associated proteins that affect different aspects of their physiology and cell biology. Nothing is known about protein(s) that interact with hTHTR-2 in intestinal epithelial cells and influence its physiological function and/or its cell biology.

Aims

The aim of this study was to identify protein partner(s) that interact with hTHTR-2 in human intestinal cells and determine the physiological/biological consequence of that interaction.

Methods

The yeast split-ubiquitin two-hybrid approach was used to screen a human intestinal cDNA library. GST-pull-down and cellular co-localization approaches were used to confirm the interaction between hTHTR-2 and the associated protein(s). The effect of such an interaction on hTHTR-2 function was examined by ³H-thiamine uptake assays.

Results

Our screening results identified the human TransMembrane 4 SuperFamily 4 (TM4SF4) as a potential interactor with hTHTR-2. This interaction was confirmed by an in vitro GST-pull-down assay, and by live-cell confocal imaging of HuTu-80 cells co-expressing hTHTR-2–GFP and mCherry–TM4SF4 (the latter displayed a significant overlap of these two proteins in intracellular vesicles and at the cell membrane). Co-expression of hTHTR-2 with TM4SF4 in HuTu-80 cells led to a significant induction in thiamine uptake. In contrast, silencing TM4SF4 with gene-specific siRNA led to a significant decrease in thiamine uptake.

Conclusions

These results show for the first time that the accessory protein TM4SF4 interacts with hTHTR-2 and influences the physiological function of the thiamine transporter.