Non‐nutritional uses of food in traditional Appalachian culture

Food has both nutritional and non‐nutritional functions and this paper reports some non‐nutritional uses of food in traditional Appalachian culture. The emphasis is upon occult and non‐occult uses of food in folk medicine. Specific examples of rituals are presented as collected in Appalachia. It is suggested that these traditions have been maintained due to the strength of the reference groups.     

Comparative analysis of genes regulated by PML/RAR alpha and PLZF/RAR alpha in response to retinoic acid using oligonucleotide arrays

Acute promyelocytic leukemia (APL) is associated with chromosomal translocations involving retinoic acid receptor alpha (RAR alpha) and its fusion partners including promyelocytic leukemia (PML) and promyelocytic leukemia zinc finger (PLZF). Using oligonucleotide arrays, we examined changes in global gene expression mediated by the ectopic expression of either PML/RAR alpha (retinoid-sensitive) or PLZF/RAR alpha (retinoid-resistant) in U937 cells. Of more than 5000 genes analyzed, 16 genes were commonly up-regulated, and 57 genes were down-regulated by both fusion proteins suggesting their role in the APL phenotype. In our APL model, for example, TNFAIP2, TNFR2, ELF4, RAR gamma, and HoxA1 were down-regulated by both fusion proteins in the absence of retinoic acid (RA). RA strongly up-regulated these genes in PML/RAR alpha, but not in PLZF/RAR alpha expressing U937 cells. Expression studies in NB4, retinoid-resistant NB4-R2, normal human CD34+ cells, and APL patient samples strongly suggest their role in the regulation of granulocytic differentiation. Furthermore, combined treatment with tumor necrosis factor alpha (TNF alpha) and RA synergistically enhanced granulocytic differentiation in NB4 cells but not in NB4-R2 cells. Our data indicate that APL pathogenesis and retinoid-induced granulocytic differentiation of APL cells involve genes in the cell death pathway, and that cooperation between the RA and TNFalpha signaling pathways exists. Targeting both the retinoid-dependent differentiation and the cell death pathways may improve leukemic therapy, especially in retinoid-resistant acute myeloid leukemia.     

Mental health of clinical staff working in high-risk epidemic and pandemic health emergencies a rapid review of the evidence and living meta-analysis

Purpose

The SARS-CoV-2 / COVID-19 pandemic has raised concerns about the potential mental health impact on frontline clinical staff. However, given that poor mental health is common in acute medical staff, we aimed to estimate the additional burden of work involving high exposure to infected patients.

Methods

We report a rapid review, meta-analysis, and living meta-analysis of studies using validated measures from outbreaks of COVID-19, Ebola, H1N1 influenza, Middle East respiratory syndrome (MERS), and severe acute respiratory syndrome (SARS).

Results

A random effects meta-analysis found that high-exposure work is not associated with an increased prevalence of above cut-off scoring (anxiety: RR = 1.30, 95% CI 0.87–1.93, Total N = 12,473; PTSD symptoms: RR = 1.16, 95% CI 0.75–1.78, Total N = 6604; depression: RR = 1.50, 95% CI 0.57–3.95, Total N = 12,224). For continuous scoring, high-exposure work was associated with only a small additional burden of acute mental health problems compared to low-exposure work (anxiety: SMD = 0.16, 95% CI 0.02–0.31, Total N = 6493; PTSD symptoms: SMD = 0.20, 95% CI 0.01–0.40, Total N = 5122; depression: SMD = 0.13, 95% CI -0.04–0.31, Total N = 4022). There was no evidence of publication bias.

Conclusion

Although epidemic and pandemic response work may add only a small additional burden, improving mental health through service management and provision of mental health services should be a priority given that baseline rates of poor mental health are already very high. As new studies emerge, they are being added to a living meta-analysis where all analysis code and data have been made freely available: https://osf.io/zs7ne/.

     

Paraoxonase polymorphisms PON1 192 and 55 and longevity in Italian centenarians and Irish nonagenarians. A pooled analysis

BACKGROUND: PON1, an arylesterase, associated with high density lipoprotein (HDL), protects low density lipoprotein (LDL) against oxidative modification. Common polymorphisms PON1 55 (L/M) and 192 (Q/R) in the PON1 gene associate with atherosclerosis and heart disease. Because long-lived people seem protected from premature vascular death, we conducted a pooled statistical analysis to assess any association between these polymorphisms and longevity in a large combined group of Italian centenarians and octo/nonagenarians from Northern Ireland (NI). MATERIALS AND METHODS: Separated DNA was available from 1479 subjects from Italy and Northern Ireland (NI). In Italy 308 centenarians (males 67, females 241, mean age 100.8, SD2.1 years) and 579 young controls (males 347, females 232, mean age 40.7, SD 12.7 years) were included in the study. In NI, 296 octo/nonagenarians (males 92, females 204, mean age 89.8, SD 5.7 years) and 296 young sex-matched subjects (mean age 13.0, SD 1.4 years) had available DNA. PON1 55 (L/M) and 192 (Q/R) polymorphisms were studied using a PCR-RFLP approach. RESULTS: There was a significant difference in PON1 192 genotypes in Italian centenarians compared to younger controls (X(2)= 6.8, df = 2 p= 0.03) and a similar but non significant trend between octo/nonagenarian and young subjects in NI (X(2) = 4.0, df=2, p=0.14). Using logistic regression analysis on the combined Italian and Irish datasets, there was a small survival advantage for centenarian and octo/nonagenarian subjects who were heterozygous for PON1 192 R allele, (OR 1.3, CI 1-1.6; p=0.04 with a stepwise increase for RR homozygous subjects (OR 1.7, CI 1.1-2.6; p = 0.02) compared to QQ subjects. Comparing R and Q alleles there was a survival advantage for octo/nonagenarian/centenarian subjects who carried the R allele (OR 1.3, CI 1.1-1.5; p = 0.007) but there was no sex-specific effect p =0.77) LL, LM and MM genotypes of PON 55 polymorphisms showed similar frequencies in Italy (39.9, 47.0, 13.1%) and Ireland (39.5, 48.6, 11.9%) with no age or sex-related differences. The PON1 192R/Q and PON55L/M loci were in strong linkage disequilibrium with a Lewontin's D' coefficient -0.928 (elderly) and -0.965 (young). There was a significant difference in haplotype frequency of these linked loci in older compared to younger subjects (Likelihood Ratio X(2) = 9.60, df = 3, p= 0.02). CONCLUSION: These data suggest a modest association between the 192R allele and longevity in two very elderly populations in two European countries. Being homozygous for 192 RR further enhances survival advantage but this effect was not found to be sex specific. This finding is of interest because the 192R allele has previously been associated with increased risk of coronary heart disease. On the other hand, the 192R allele shows higher enzymatic activity, using paraoxon as substrate, and we postulate that its role in the metabolism of potentially toxic chemicals or other metabolic pathways may be important in survival to very old age.     

Glycemia (or, in women, estimated glucose disposal rate) predict lower extremity arterial disease events in type 1 diabetes

The purpose of this study was to determine the predictors of lower extremity arterial disease (LEAD) events in a type 1 diabetes population. Data are from the Pittsburgh Epidemiology of Diabetes Complications Study of childhood onset type 1 diabetes. At baseline, the study population had a mean age 28 (range, 8 to 47) years and duration 19 (range, 7 to 37) years. LEAD events, assessed by questionnaire or clinical examination, were defined as claudication (Rose questionnaire), foot ulceration, or lower extremity amputation. Estimated glucose disposal rate (eGDR), a measure of insulin resistance, was calculated from glycosylated hemoglobin (HbA(1)), waist-to-hip ratio (WHR), and hypertension using an equation previously validated with hyperinsulinemic euglycemic clamp studies. There were incident LEAD events in 70 of 586 subjects during 10 years follow-up, giving an incidence density of 1.3 events/100 person-years. Incidence did not differ by gender. Major predictors of LEAD events were diabetes duration, low-density lipoprotein-cholesterol (LDL-C), heart rate, eGDR, log albumin excretion rate (AER), systolic blood pressure (SBP), hypertension, proliferative retinopathy, distal symmetric polyneuropathy, and overt nephropathy (each P <.001). HbA(1), low ankle brachial index (ABI) (<0.9), and a high ankle brachial difference (ABD) (SBP > or = 75 mm Hg) also predicted LEAD events. Cox modeling suggested that duration (P <.001), HbA(1) (P <.001), hypertension (P =.006), log albumin excretion rate (P =.011), and heart rate (P =.028) predicted events independently. The overall model with HbA(1) and hypertension was significantly better than with eGDR, while the alternate models in men were similar. In women, the model with eGDR showed a significantly better fit. Glycemia, insulin resistance, hypertension and renal disease are powerful predictors of symptomatic lower extremity arterial disease in type 1 diabetes.