ApoC-III bound to apoB-containing lipoproteins increase with insulin resistance in Cherokee Indian youth

Because Native Americans are predisposed to obesity and type 2 diabetes associated with coronary artery disease, we assessed whether apoC-III bound to apoB-containing (LpB:C-III) and apoA-containing (LpA:C-III) lipoproteins, total apoC-III, apoB, and plasma lipids are associated with insulin resistance, body mass index (BMI), and waist circumference in Cherokee children and adolescents aged 5 to 19 years (n = 975). A cross-sectional analysis was done to determine associations of the lipoproteins with the homeostasis index (HOMA-IR) and BMI. When the data were grouped by quartiles for HOMA-IR and separated by three 5-year age groups (5-9, 10-14, and 15-19 years), the trend for LpB:C-III, triglyceride, and BMI z score to increase was significant for all age groups and both genders (P < .001). The trend to increase LpB:C-III with age was greater in boys (P < .0001) than in girls (P < .05) who tended to plateau after the age of 10 years. In contrast, the ratio of LpA:C-III to LpB:C-III decreased and the decrease was greater in boys (P < .0001) than girls (P < .01). Body mass index z score and waist circumference were correlated with LpB:C-III, triglyceride, apoB, and non-high-density lipoprotein cholesterol within each gender (P < .001). In multiple regression models, LpB:C-III, the dependent variable, was associated with HOMA-IR for both genders. We conclude that increases in LpB:C-III in childhood and adolescence are associated with insulin resistance and obesity supporting the need for prevention programs.     

Anal sphincter reconstruction in the elderly: Does advancing age affect outcome?

PURPOSE: This study was designed to determine whether advancing age affects outcome after anal sphincter reconstruction. METHOD: Anal sphincter reconstruction, performed on patients 55 years of age and older, was reviewed to determine if functional outcome was adversely affected by advancing age. A subgroup of patients was studied with anal manometry before and after repair and with pudendal nerve terminal motor latency (PNTML) before surgery. Results were compared with a younger group of patients. RESULTS: Between July 1986 and July 1991, 14 patients, ages ranging from 55 to 81, underwent anal sphincter reconstruction using an overlapping muscle repair. Ten patients were incontinent of solid stool and four of liquid stool. Improvement was seen in 13 of 14 patients: 7 (50 percent) complete control, 3 (21 percent) incontinent to flatus, and 4 (29 percent) incontinent to liquid stools (including the patient who failed to improve). Ten patients were studied with a continuous pull-out manometric technique and PNTML: one was not improved. There was minimum change in mean maximum resting pressure (35.0–37.9 mmHg). Mean maximum squeezing pressure increased from 66 to 75 mmHg overall. Patients with complete control had a mean maximum squeezing pressure of 81 mmHg compared with 60 mmHg in patients with residual incontinence. Mean anterior anal sphincter length increased from 2.92 cm to 331 cm. PNTML was normal (2.0±0.2) on one or both sides in all nine patients who improved (average, 2.1). The patient who failed to improve had abnormal nerve function bilaterally (2.4, 2.7). CONCLUSION: Anal sphincter reconstruction can be performed in elderly patients with improvements in the majority of patients. Total control can be achieved by restoring maximum squeezing pressure in a patient with normal pudendal nerve function.Poster presentation at the meeting of The American Society of Colon and Rectal Surgeons, San Francisco, California, June 7 to 12, 1992.     

Confirmatory factor analysis and measurement invariance by gender,age and levels of psychological distress of the short TEMPS-A

Background

The Temperament Evaluation of Memphis, Pisa, Paris and San Diego – Autoquestionnaire (TEMPS-A) is a widely used self-reported tool aimed at measuring the affective temperaments that define the bipolar spectrum, with cyclothymic, depressive, irritable, hyperthymic, and anxious subscales. Confirmatory factor analysis (CFA) was rarely used to confirm the expected five-factor model. Measurement invariance was never tested.

Methods

Cross-sectional, survey design involving 649 Italian college students (males: 47%). The short 39-item TEMPS-A and the 12-item General Health Questionnaire (GHQ-12) were used as measures of the affective temperaments and of psychological distress, respectively. CFA was applied to the TEMPS-A. Measurement invariance by gender, age and levels of psychological distress on the GHQ-12 was calculated with the establishment of subsequent equivalence constraints in the model parameters across groups.

Results

The expected five-factor model had the best fit for all CFA indexes. Configural, metric and scalar invariance of the five-factor model of the TEMPS-A was proved across gender, age and levels of psychological distress of the participants. The hyperthymic temperament subscale has low or no links with the other affective temperament subscales, which were interrelated with medium to large effect sizes.

Limitations

College students might be not representative of the general population. No information on the clinical status of the students was available beyond self-report data.

Conclusion

The study proved the measurement invariance of the (short) TEMPS-A, which is a pre-requisite to compare groups or individuals in cross-sectional and longitudinal surveys. Generalizability cannot be assumed without replication of the findings in clinical samples.     

A subset of anti-rotavirus antibodies directed against the viral protein VP7 predicts the onset of celiac disease and induces typical features of the disease in the intestinal epithelial cell line T84

Celiac disease (CD) is an autoimmune disorder of the small intestine triggered by environmental factors in genetically predisposed individuals. A strong association between type 1 diabetes (T1DM) and CD has been reported. We have previously shown that rotavirus infection may be involved in the pathogenesis of CD through a mechanism of molecular mimicry. Indeed, we identified a subset of anti-transglutaminase IgA antibodies that recognize the rotavirus viral protein VP7. In this study, we aimed at evaluating whether such antibodies may predict the onset of CD in children affected by T1DM. Moreover, to further analyze the link between rotavirus infection and pathogenesis of CD, we analyzed the effect of anti-rotavirus VP7 antibodies on T84 intestinal epithelial cells using the gene-array technique, complemented by the analysis of molecules secreted in the supernatant of stimulated cells. We found that anti-rotavirus VP7 antibodies are present in the vast majority (81 %) of T1DM-CD tested sera, but are detectable also in a fraction (27 %) of T1DM children without CD. Moreover, we found that anti-rotavirus VP7 antibodies are present before the CD onset, preceding the detection of anti-tTG and anti-endomysium antibodies. The gene-array analysis showed that purified anti-rotavirus VP7 antibodies modulate genes that are involved in apoptosis, inflammation, and alteration of the epithelial barrier integrity in intestinal epithelial cells, all typical features of CD. Taken together, these new data further support the involvement of rotavirus infection in the pathogenesis of CD and suggest a predictive role of anti-rotavirus VP7 antibodies.     

Long pentraxin‐3 as an epithelial–stromal fibroblast growth factor‐targeting inhibitor in prostate cancer

Fibroblast growth factors (FGFs) exert autocrine/paracrine functions in prostate cancer by stimulating angiogenesis and tumour growth. Here dihydrotestosterone (DHT) up‐regulates FGF2 and FGF8b production in murine TRAMP‐C2 prostate cancer cells, activating a FGF‐dependent autocrine loop of stimulation. The soluble pattern recognition receptor long pentraxin‐3 (PTX3) acts as a natural FGF antagonist that binds FGF2 and FGF8b via its N‐terminal domain. We demonstrate that recombinant PTX3 protein and the PTX3‐derived pentapeptide Ac‐ARPCA‐NH₂ abolish the mitogenic response of murine TRAMP‐C2 cells and human LNCaP prostate cancer cells to DHT and FGFs. Also, PTX3 hampers the angiogenic activity of DHT‐activated TRAMP‐C2 cells on the chick embryo chorioallantoic membrane (CAM). Accordingly, human PTX3 overexpression inhibits the mitogenic activity exerted by DHT or FGFs on hPTX3_TRAMP‐C2 cell transfectants and their angiogenic activity. Also, hPTX3_TRAMP‐C2 cells show a dramatic decrease of their angiogenic and tumourigenic potential when grafted in syngeneic or immunodeficient athymic male mice. A similar inhibitory effect is observed when TRAMP‐C2 cells overexpress only the FGF‐binding N‐terminal PTX3 domain. In keeping with the anti‐tumour activity of PTX3 in experimental prostate cancer, immunohistochemical analysis of prostate needle biopsies from primary prostate adenocarcinoma patients shows that parenchymal PTX3 expression, abundant in basal cells of normal glands, is lost in high‐grade prostatic intraepithelial neoplasia and in invasive tumour areas. These results identify PTX3 as a potent FGF antagonist endowed with anti‐angiogenic and anti‐neoplastic activity in prostate cancer. Copyright © 2013 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.     

Neurological comorbidity and severity of COVID-19

Journal of Neurology - Neurological symptoms of COVID-19 patients have been recently described. However, no comprehensive data have been reported on pre-existing neurological comorbidities and...