In Los Angeles County, California, 142 cases of human listeriosis were reported from January 1 through August 15, 1985. Ninety-three cases (65.5 percent) occurred in pregnant women or their offspring, and 49 (34.5 percent) in nonpregnant adults. There were 48 deaths: 20 fetuses, 10 neonates, and 18 nonpregnant adults. Of the nonpregnant adults, 98 percent (48 of 49) had a known predisposing condition. Eighty-seven percent (81 of 93) of the maternal/neonatal cases were Hispanic. Of the Listeria monocytogenes isolates available for study, 82 percent (86 of 105) were serotype 4b, of which 63 of 86 (73 percent) were the same phage type. A case-control study implicated Mexican-style soft cheese (odds ratio, 5.5; 95 percent confidence interval, 1.2 to 24.8) as the vehicle of infection; a second case-control study showed an association with one brand (Brand A) of Mexican-style soft cheese (odds ratio, 8.5; 95 percent confidence interval, 2.4 to 26.2). Laboratory study confirmed the presence of L. monocytogenes serogroup 4b of the epidemic phage type in Brand A Mexican-style cheese. In mid-June, all Brand A cheese was recalled and the factory was closed. An investigation of the cheese plant suggested that the cheese was commonly contaminated with unpasteurized milk. We conclude that the epidemic of listeriosis was caused by ingestion of Brand A cheese contaminated by one phage type of L. monocytogenes serotype 4b.

To study the alterations of sleep quality and circadian rhythm genes expressions upon elderly thyroid nodule patients, the risk factors associated with thyroid malignancies, and the potential relationship involved. The elderly people enrolled in our study were divided into three groups according to the thyroid histopathology: malignant nodule group, benign nodule group, and normal group, and the clinical data and sleep quality were collected. Among the patients of surgery, 56 fresh thyroid tissues were collected for real-time PCR, immunohistochemistry and western blotting analysis of CLOCK, BMAL1, CRYs and PERs. Poor sleep quality, sleep latency and daytime dysfunction were the independent risk factors of malignant nodule after adjusted by other impacts. The expression levels of CLOCK, BMAL1 and PER2 in thyroid malignant group were significantly higher than benign and normal groups, while CRY2 was decreased, p < 0.05. In addition, CLOCK and BMAL1 protein levels were positively correlated with PSQI of corresponding patients and CRY2 was negatively correlated. Circadian rhythm genes mainly altered in malignant nodules, and sleep disorders may be involved in the occurrence of elderly thyroid malignancy through the high expressions of CLOCK and BMAL1, and low expression of CRY2.

This paper studies the expression of proinflammatory cytokines such as IL-1β, IL-6, TNF-α, and IFN-γ and anti-inflammatory cytokines such as IL-10 in diabetic rat aortas, the effects of resveratrol on these cytokines, and the potential epigenetic mechanisms involved. The experiment was performed on rats divided into four groups: normal group (NC), normal interventional group (NB), diabetic group (DM), and diabetic interventional group (DB). The NB and DB groups were treated with resveratrol. After more than 3 months, the rats' aortas were removed and analyzed for cytokines by using immunohistochemistry, Western blotting, real-time PCR, and methylation-specific PCR. Histological localization of these cytokines was mainly found in the arterial intima of diabetic rats. The protein and mRNA expression levels of IL-1β, IL-6, TNF-α, and IFN-γ were significantly higher in the DM group than in the NC group (p < 0.05), whereas in the resveratrol-treated groups (NB and DB), the levels were relatively lower than those in the corresponding groups. The DM group showed reduced levels of DNA methylation at the specific cytosine phosphate guanosine sites of IL-1β, IL-6, TNF-α, and IFN-γ, relative to those in the NC group (p < 0.01), and these levels were increased by resveratrol. In contrast, IL-10 was dramatically methylated and showed decreased expression in response to high glucose, and resveratrol reversed this effect. These results demonstrate that the inflammatory response is involved in diabetic macroangiopathy. Resveratrol inhibits the expression of proinflammatory cytokines and thus may have a protective effect on the aorta in hyperglycemia. Thus, DNA methylation, an epigenetic gene silencing signal, may be responsible for these two phenomena.

The half-life of STK1c may be an important tool in the clinical evaluation of surgical response in patients with lung cancer. STK1c may also be beneficial in the early detection of lung cancer.

AimGastrointestinal discomfort is the most common adverse event in metformin treatment for type 2 diabetes. The mechanism of action of metformin is associated with gut microbiota. However, the gut microbial community structure related to metformin-induced gastrointestinal adverse events remains unclear. This study aimed to investigate it.Methods50 patients with newly diagnosed diabetes were treated with metformin 1500mg/d for 12 weeks. The patients were divided into two groups according to whether gastrointestinal adverse events occurred (group B) or did not occur (group A) after treatment. The fecal bacterial communities and short-chain fatty acids (SCFAs) were sequenced and compared. 70 diabetes mice were randomly divided into 8 groups and treated with metformin (Met), clindamycin (Clin) and/or SCFA, which were the Met+/Clin+, Met+/Clin-, Met-/Clin+, Met-/Clin-, Met+/SCFA+, Met+/SCFA-, Met-/SCFA+ and Met-/SCFA- group. After 4 weeks of metformin treatment, blood glucose, food intake, fecal SCFAs, gut microbiota and gut hormones were measured.ResultsMetformin increased the abundance of Phascolarctobacterium, Intestinimonas and Clostridium III. Functional prediction analysis showed that the propanoate metabolism pathway was significantly up-regulated. The concentrations of acetic acid and propanoic acid in feces were significantly increased. The abundance of Clostridium sensu stricto, Streptococcus and Akkermansia induced by metformin in group B was higher than that in group A. The propanoate metabolism pathway and propanoic acid in feces were significantly up-regulated in group B. In the animal experiments, the food intake decreased and glucose control increased in metformin groups compared with those in the control groups. The total GLP-1 level in the Met+/Clin- group was significantly higher than that in the Met-/Clin- group, while there was no statistical difference between the Met-/Clin- and Met+/Clin+ group. The total GLP-1 level in the Met-/SCFA+ group was significantly higher than that in the Met-/SCFA-group, while the levels of total GLP-1 and active GLP-1 in the Met+/SCFA- group and the Met+/SCFA+ group were significantly higher than those in the Met-/SCFA-group.ConclusionsOur data suggest that metformin promotes the secretion of intestinal hormones such as GLP-1 by increasing the abundance of SCFA-producing bacteria, which not only plays an anti-diabetic role, but also may causes gastrointestinal adverse events.

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Objective The aim of this study was to investigate the effect of Von Willebrand factor (VWF) on high‐fat diet (HFD)‐induced hepatic steatosis, insulin resistance, and inflammation in mice. Methods The expression of VWF was detected in obese mice. Wild‐type and VWF knockout mice were fed a normal chow diet or an HFD, and then biomedical, histological, and metabolic analyses were conducted to identify pathologic alterations. Inflammatory cytokine levels and the number of hepatic macrophages were determined in these mice fed an HFD. Results VWF expression was significantly increased in obese mice. VWF−/− mice were less obese and had improved hepatic steatosis, balance of lipid metabolism, and insulin resistance in response to HFD. Furthermore, VWF deficiency attenuated HFD‐induced systemic and hepatic inflammation. In addition, VWF deficiency rescued the abnormal accumulation of hepatic macrophages. Conclusions These data demonstrated VWF deficiency improves hepatic steatosis, insulin resistance, and inflammation. Furthermore, the protective effects are mediated via regulation of hepatic macrophages.

Assessment of multiple factors is necessary when evaluating the success rate of myringoplasty Dear Editors,We would like to address the manuscript by Carr et al. entitled 'Factors affecting myringoplasty success'. 1 This is an interesting study and constitutes excellent work. The authors evaluated the success of myringoplasty from the following five perspectives: experience of the surgeon, dry ear or not, the condition of the contralateral middle ear, perforation size, and the simultaneous performance of cortical mastoidectomy. It was concluded that, in adults, a significant association was evident between the tympanic membrane perforation site and the closure rate. Anterior and subtotal perforations had significantly lower closure rates. None of the factors evaluated significantly influenced tympanic membrane closure in a paediatric group. However, we believe that the factors assessed were not comprehensive. Also, the use of different graft materials has confused the findings.The authors write, in the Methods section:'Inclusion criteria comprised perforations of the pars tensa, all age groups, and cortical mastoidectomy and myringoplasty for non-cholesteatoma ears. Exclusion criteria comprised cholesteatoma surgery and concomitant ossiculoplasty. … Potential influencing factors were surgeon grade (consultant, associate specialist or registrar); pre-operative condition of the ipsilateral middle ear (inactive or active chronic otitis media, with persistent or intermittent discharge); pre-operative condition of the contralateral middle ear (normal, otitis media with effusion, inactive chronic otitis media or active chronic otitis media); perforation site (anterior, posterior, inferior or subtotal); perforation size (0-20 per cent, 21-40 per cent, 41-60 per cent or subtotal); and simultaneous cortical mastoidectomy. The indication for a cortical mastoidectomy was myringoplasty in the presence of an actively discharging ear or a revision paediatric case'.The authors did not assess the Eustachian tube or record concomitant myringosclerosis. Furukawa et al. suggested that removal of myringosclerosis at the edge of a perforation was beneficial when simple underlay myringoplasty was planned, improving the operative success rate and postoperative hearing threshold, especially when the myringosclerosis extended over the entire tympanic membrane. 2 Migirov and Volkov believed that appropriate freshening of the perforation edges, with removal of sclerotic plaques, improved the success rate when tympanoplasty was performed in patients with concomitant myringosclerosis. 3 Pinar et al. found that the absence of myringosclerosis and a low middle-ear risk index were significantly (and independently) prognostic of successful tympanoplasty. 4 The Eustachian tube plays a significant role in the success of myringoplasty. One effect of Eustachian tube dysfunction in paediatric populations is that the middle-ear cavity is under negative pressure, which can cause retraction of the tympanic membrane, triggering failure of myringoplasty....