Hemin enhances the in vitro growth of primitive erythroid progenitor cells

Since exogenous hemin has been shown to exert a variety of stimulatory effects on erythroid cells, including the augmentation of hemoglobin synthesis, we determined its effect on early stages of erythroid development by employing clonal cells assays. The addition of hemin at a concentration of 2 X 10(-4) M to cultures of normal murine marrow substantially increased the observed number of primitive BFU-E, which was in contrast to its lack of an effect on more mature erythroid colony-forming cells. This cell-specific enhancement of primitive BFU-E resulted in marrow frequencies equivalent to or exceeding those reported in the presence of "burst-promoting activity." In the presence of hemin, the number of BFU-E was also observed to be linearly related to the number of cells plated at very low plating densities, and the cell titration curve was observed to extrapolate to the origin. The evidence suggests that hemin may be a primary growth regulator of early developmental stages of erythroid progenitor cells.     

Assessment of the mutagenicity of dichloroacetic acid in lacI transgenic B6C3F1 mouse liver

Dichloroacetic acid (DCA) is a chlorination byproduct found in finished drinking water. When administered in drinking water this chemical has been shown to produce hepatocellular adenomas and carcinomas in B6C3F1 mice over the animal's lifetime. In this study, we investigated whether mutant frequencies were increased in mouse liver using treatment protocols that yielded significant tumor induction. DCA was administered continuously at either 1.0 or 3.5 g/l in drinking water to male transgenic B6C3F1 mice harboring the bacterial lacI gene. Groups of five or six animals were killed at 4, 10 or 60 weeks and livers removed. At both 4 and 10 weeks of treatment, there was no significant difference in mutant frequency between the treated and control animals at either dose level. At 60 weeks, mice treated with 1.0 g/l DCA showed a 1.3-fold increase in mutant frequency over concurrent controls (P = 0.05). Mice treated with 3.5 g/l DCA for 60 weeks had a 2.3-fold increase in mutant frequency over the concurrent controls (P = 0.002). The mutation spectrum recovered from mice treated with 3.5 g/l DCA for 60 weeks contained G:C-->A:T transitions (32.79%) and G:C-->T:A transversions (21.31%). In contrast, G:C-->A:T transitions comprised 53.19% of the recovered mutants among control animals. Although only 19.15% of mutations among the controls were at T:A sites, 32.79% of the mutations from DCA-treated animals were at T:A sites. This is consistent with the previous observation that the proportion of mutations at T:A sites in codon 61 of the H-ras gene was increased in DCA-induced liver tumors in B6C3F1 mice. The present study demonstrates DCA-associated mutagenicity in the mouse liver under conditions in which DCA produces hepatic tumors.      

Fatty acid balance studies in term infants fed formula milk containing long-chain polyunsaturated fatty acids

Long-chain polyunsaturated fatty acids (LCP) are thought to be required for optimal nervous system development in the newborn. A commercial milk formula containing LCP (Aptamil-LCP) with a fatty acid profile closely resembling breast milk, has recently been introduced for term infants. The absorption of fatty acids in term infants was examined in a double-blind randomized controlled trial comparing Aptamil-LCP ( n = 20) and standard Aptamil ( n = 20). Formula-fed newborn infants were studied from birth for 14 d. Fat balances (3 d) were performed from d 10. A 3-d stool collection was performed from d 10 in a parallel breastfed group ( n = 21). Plasma samples were taken on d 6. Median fat excretion (mg kg⁻¹) was 897.1, 615.0 and 355.2 with Aptamil, Aptamil-LCP and breastfeeding, respectively. The median total fat absorption coefficient in Aptamil-LCP-fed infants was higher than in those fed standard Aptamil ( p < 0:01). These findings were accounted for by differences in the excretion and absorption of long-chain saturated fatty acids (C14:0, C16:0 and C18:0). Higher fat excretion was associated with bulkier and firmer stools. Only trace amounts of LCP were detected in the stools of all groups. This accounted for less than 4% of dietary intake in Aptamil-LCP-fed infants. No differences in the utilization of LCP from Aptamil-LCP and breast milk feeding were apparent. Plasma phospholipid fatty acid composition data reflected differences in dietary LCP intake. Thus, PL LCP levels were highest in the breastfed infants and lowest in the Aptamil-fed infants, with values for the Aptamil-LCP-fed group falling in between.     

代谢综合症基线调查

目的：通过对豫宛市30岁以上人群代谢综合症（MS）发病率的词查、统计和分析，旨在唤起人们对此病的重视和预防。方法：利用年度体检之机采用三级分组法对30岁以上人群进行有关MS指标的检测和统计，依据亚洲及我国体重指数标准及2004年中华医学会糖尿病分会诊断代谢综合症标准。共计调查人数3987人（男1981人，女2006人）。结果：30岁以上MS患病率，青年有10％～13％，中老年后可渐增至20％～30％。结论：MS是中老年多见的代谢异常疾病。已严重威胁着人们的生命健康。     

Measurement of alcohol craving

Despite considerable research activity and application in treatment, the construct of craving remains poorly understood. We propose that cravings and urges are cognitive–emotional events in time, characterised by frequency, duration, intensity and salience. Commonly used measures of alcohol craving are reviewed, and their strengths and weaknesses identified. Most measures confound craving with behaviours, or with separable cognitive phenomena such as expectancies, intentions, or perceived behavioural control. These confounds have limited our advances in understanding the determinants and consequences of craving. Based on the criteria applied in this review, among the better performing multi-item measures are the Penn Alcohol Craving Scale and Obsessive subscale of the Obsessive–Compulsive Drinking Scale. Optimal assessment strategies are likely to involve daily assessments of peak intensity of cravings, desires or urges and of the frequency and duration of craving episodes. Of particular interest are measures of intensity at times when individuals are at risk of drinking or of other functional impacts from craving.     

Efficacy of an eConsult service to cure hepatitis C in primary care

In 2016, an eConsult service was developed within a safety net health system to expand access to hepatitis C (HCV) treatment in the primary care setting. The eConsult system provides individualized treatment recommendations from specially trained primary care pharmacists and primary care physicians to primary care providers with less experience in the rapidly changing treatment of HCV. Since its launch, this service has had a large impact in expanding care to a largely homeless and low-income urban population within our health system. We now aim to evaluate its efficacy in curing HCV. In this retrospective cohort study, we describe rates of sustained virologic response 12 weeks after treatment completion (SVR12) for those who received primary care-based HCV treatment through the eConsult system with those who were treated in primary care independent of an eConsult from 2017 to 2019. We found there was no significant difference in the proportion of patients who achieved SVR12 between the two groups. Overall, >90% of patients who received treatment achieved SVR12. Approximately 40% of patients treated for HCV received an eConsult, suggesting utility of the eConsult in expanding access and coordinating treatment for patients within our network.     

Impact of intrapeptide epitope location on CD8 T cell recognition: implications for design of overlapping peptide panels

BACKGROUND: Antigen-specific CD8 T cells following infection or immunization are typically assessed by measuring interferon-gamma production after stimulation with overlapping peptides spanning the region of interest. The effect of epitope location within such peptides is not known but may influence recognition. OBJECTIVE: To examine if peptides containing the appropriate C-terminal anchor amino acid residue would provide more sensitive detection of T cell responses. The impact was examined of epitope location within overlapping peptides on recognition of epitope-specific CD8 T cell responses. METHODS: C-terminal amino acid residues were analyzed in well-defined optimal epitopes for HIV, Epstein-Barr virus, cytomegalovirus and influenza and in peptide-binding motifs. Recognition of known epitopes within longer synthesized peptides by peripheral blood mononuclear cells or CD8 T cell lines was tested using interferon-gamma Elispot at various peptide concentrations. RESULTS: Only 9 of 20 amino acids served as the C-terminal anchor position in 96% of described optimal epitopes and in 95% of peptide-binding motifs. A CD8 T cell response to an epitope within a longer peptide is best detected when the epitope is situated at the C-terminal end of the longer peptide, both when using peptides designed to include the optimal epitope at every possible position and when comparing responses towards optimal epitopes and corresponding overlapping peptides in a larger group of subjects. CONCLUSION: When using overlapping peptides to screen for CD8 T cell responses, more sensitive detection will be achieved using known C-terminal anchor amino acid residues at the C-terminus.