Association of obesity with illness severity in hospitalized patients with COVID-19: A retrospective cohort study

BackgroundAlthough recent studies have shown an association between obesity and adverse coronavirus disease 2019 (COVID-19) patient outcomes, there is a paucity in large studies focusing on hospitalized patients. We aimed to analyze outcomes associated with obesity in a large cohort of hospitalized COVID-19 patients.MethodsWe performed a retrospective study at a tertiary care health system of adult patients with COVID-19 who were admitted between March 1 and April 30, 2020. Patients were stratified by body mass index (BMI) into obese (BMI ≥ 30 kg/m 2) and non-obese (BMI < 30 kg/m 2) cohorts. Primary outcomes were mortality, intensive care unit (ICU) admission, intubation, and 30-day readmission.ResultsA total of 1983 patients were included of whom 1031 (51.9%) had obesity and 952 (48.9%) did not have obesity. Patients with obesity were younger (P < 0.001), more likely to be female (P < 0.001) and African American (P < 0.001) compared to patients without obesity. Multivariable logistic models adjusting for differences in age, sex, race, medical comorbidities, and treatment modalities revealed no difference in 60-day mortality and 30-day readmission between obese and non-obese groups. In these models, patients with obesity had increased odds of ICU admission (adjusted OR, 1.37; 95% CI, 1.07?1.76; P = 0.012) and intubation (adjusted OR, 1.37; 95% CI, 1.04?1.80; P = 0.026).ConclusionsObesity in patients with COVID-19 is independently associated with increased risk for ICU admission and intubation. Recognizing that obesity impacts morbidity in this manner is crucial for appropriate management of COVID-19 patients.     

CYP1B1基因敲除对成年小鼠肝脏脂肪代谢的影响及可能机制

目的探讨CYP1B1对高脂膳食诱导的成年小鼠脂肪代谢的作用。方法 CYP1B1基因敲除(KO)和野生型(WT)雄性成年C57/BL小鼠(6 w龄)各16只,给予低脂(LFD,30%)、高脂肪(HFD,60%)饲料共6 w。小鼠处死后取血清、附睾脂肪和肝脏组织检测相应的生化和分子生物学指标。结果 6 w高脂膳食后,KO小鼠能量摄入总量稍高于WT小鼠,但其体重增量和附睾脂肪组织重量均显著低于WT小鼠;WT小鼠脂肪细胞直径明显大于KO小鼠,且血糖、血清及肝脏组织中甘油三酯(TG)水平亦明显高于KO小鼠;肝脏组织RT-PCR结果显示,CYP1B1基因敲除后,启动脂肪形成的核因子及脂肪合成相关基因如CD36、SREBP1c、SCD1等表达下降,而调控脂肪氧化分解的基因如CPT-1α,UCP-2表达显著上升;蛋白印迹结果显示,CYP1B1基因敲除增强腺苷-磷酸激酶(AMPK)的磷酸化。结论 CYP1B1基因敲除对成年小鼠营养性肥胖的保护作用可能与AMPK磷酸化增强并调控肝脏中脂肪代谢相关基因的表达有关。     

荧光原位杂交技术分析人结肠菌群方法研究

建立荧光原位杂交技术分析人体内结肠菌群的方法。取受试者新鲜粪便 ,选用 5种特异性的 16SrRNA寡核苷酸探针 ,检测粪便样本收集后的保存时间、温度 ,离心条件及样本固定液存放时间对杂交计数结果的影响。结果建立最佳实验条件为 :粪便样本收集后应尽快在 4℃下保存 ,放置时间不要超过 12小时即作处理 ;样本的适宜离心条件为 70 0g 2分钟 ;样本用多聚甲醛固定后在 - 80℃下存放时间不要超过 5个月。该方法具有较好的稳定性 ,可以有效地检出个体之间结肠菌群的差异。     

Alaska Native Cancer epidemiology in the Arctic

Cancer incidence and its possible relation to environmental contaminants, including radiation, continues to be a perceived health threat for the arctic-dwelling Alaska Native (Inupiat Eskimo) people despite the lack of a direct link to high-dose exposure. To better understand this concern, all known malignancies diagnosed in this population (n = 177) in three consecutive eight-year periods (1971–1994) were evaluated.The most recent average incidence rate (age-adjusted to world standard population) of 315 per 100 000 (95% confidence interval, CI = 248–382) represents a 33% surge (albeit non-significant) in Alaska Native cancer incidence over the initial period studied. The male rate 366 (95% CI = 266–466) for the same period exceeds the female rate 258 (95% CI = 169–347) by 42%. Two patterns of cancer incidence are seen at the village level. One, a 24 y upward trend found in the villages of Barrow, Point Hope and Kaktovik (combined rate of increase significant [P = 0.047]) associated with lung cancer; and the other, a stable trend over the past 16 y, associated with colon and rectal cancer. Lung cancer is the predominant cancer by site and is primarily a male disease. The recent male lung cancer incidence rate of 137 (95% CI = 73–201) exceeds the female rate by greater than five times. Total lung cancer cases are primarily confined to four villages where the incidence significantly (P = 0.0043) exceeds the remaining population. The major female cancers are colon/rectal and breast with cancer of the cervix virtually eliminated. Breast cancer is found primarily in two villages where its excess is significant (P = 0.025).Inupiat Eskimo cancer epidemiology is unique, differing from both the Alaska Native and other Circumpolar populations. At present, this uniqueness cannot be explained by an overt environmental contaminant exposure. Although tobacco very likely plays a central role, it by itself cannot fully explain the extremely high male lung cancer rate and why only specific villages are affected. Genetic predisposition and environmental factors may play a synergistic role as cofactors. A cooperative investigative effort with the Inupiat population is indicated and may go a long way in reducing cancer concern in the region.     

Effects of therapeutic doses of lactulose vs. polyethylene glycol on isotopic colonic transit

Background Lactulose and polyethylene glycol are osmotic agents used to treat idiopathic chronic constipation. Aim To compare the effects of low doses of lactulose and PEG 4000 on transit time measured by scintigraphy in normal subjects. Methods For 5 days, 10 healthy subjects received either 10 g b.d. of lactulose or PEG 4000 in a randomized, double‐blind, crossover study. On the evening of day 4, they took a capsule containing Amberlite resin pellets labelled with ¹¹¹In. On day 5, after a 1000 kcal test meal labelled with 99Tcm, gastric, small bowel and colonic transits were measured. Results Gastric emptying and small bowel transit time were not different. Ascending colon emptying curve was significantly accelerated with lactulose in comparison with polyethylene glycol (P = 0.001) and, respectively, 50 ± 18% vs. 35 ± 18% of the radioactivity had left the ascending colon at the end of the study (P < 0.05). The descending colon filling curves, variations in the geometric centre and numbers of scintigraphic movements were not different. Conclusions In healthy subjects, in comparison to PEG 4000, usual therapeutic doses of lactulose significantly accelerate ascending colon emptying. This result supports a stimulating motor effect of colonic fermentation of lactulose.     

Acute toxicity and bioaccumulation of arsenic in freshwater clam Corbicula fluminea

Arsenic is a potent human carcinogen of skin, lung, and urinary bladder. Freshwater clam Corbicula fluminea is a commercially important native species in Taiwan. C. fluminea is also a suitable biomonitoring test organism. Little is known, however, about the actual effects of arsenic on C. fluminea. The objectives of this study were to provide information on the acute toxicity and bioaccumulation kinetics of arsenic in C. fluminea. We carried out a 14-day exposure experiment to obtain bioaccumulation parameters. Uptake was very rapid when C. fluminea was first exposed and then slightly decayed during the uptake phase of the experiment and an uptake rate constant of 1.718 +/- 6.70 (mean +/- SE) mL g(-1) d(-1) was estimated. The elimination of arsenic from C. fluminea obeyed first-order depuration kinetics (r(2) = 0.85, p < 0.05) with a calculated half-life of 6.80 days. The derived bioaccumulation factor of 16.84 suggests that arsenic has a high potential for bioaccumulation in C. fluminea. This had important implications for dietary exposure of arsenic to humans who eat contaminated clams, because the soft tissue usually constitutes the majority of tissue consumed. The 96-h LC50 value was estimated to be 20.74 (95% CI: 11.74-30.79) mg L(-1) obtained from a 7-day acute toxicity bioassay. We also kinetically linked an acute toxicity model and a Hill sigmoid model to reconstruct an internal effect concentration based dose-response profile to assess the effect of soft tissue arsenic burden on the C. fluminea mortality. This result could be used to support the establishment of an ecological risk assessment to prevent possible ecosystem and human health consequences.     

Shikonin derivatives inhibited LPS-induced NOS in RAW 264.7 cells via downregulation of MAPK/NF-kappaB signaling

AIM OF THE STUDY: Shikonin/alkannin (SA) derivatives, analogs of naphthoquinone pigments, are the major components of root extracts of the Chinese medicinal herb (Lithospermum erythrorhizon; LE) and widely distributed in several folk medicines. In the present study, the effect and the underline molecular mechanism of shikonin derivatives isolated from root extracts of Lithospermum euchroma on lipopolysaccharide (LPS)-induced inflammatory response were investigated. MATERIALS AND METHODS: Effects of five SA derivatives, including SA, acetylshikonin, beta,beta-dimethylacrylshikonin, 5,8-dihydroxy-1.4-naphthoquinone, and 1,4-naphthoquinone on LPS-induced nitric oxide (NO) and prostaglandin E2 (PGE2) production in mouse macrophage RAW264.7 cells were examined. RESULTS: Data suggested that SA derivatives inhibited LPS-induced NO and PGE(2) production, and iNOS protein expression. RT-PCR analysis showed that SA derivatives diminished LPS-induced iNOS mRNA expression. Moreover, the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 in LPS-stimulated RAW 264.7 cells was concentration-dependently suppressed by SA derivatives. SA inhibited NF-kappaB activation by prevention of the degradation of inhibitory factor-kappaB and p65 level in nuclear fractions induced by LPS. CONCLUSIONS: Taken together, these results suggest that the anti-inflammatory properties of SA derivatives might result from inhibition of iNOS protein expression through the downregulation of NF-kappaB activation via suppression of phosphorylation of ERK, in LPS-stimulated RAW 264.7 cells.     

Surgical treatment of coarctation of the aorta and interrupted aortic arch

From December, 1984, through April, 1987, ten infants with coarctation of the aorta and six with interrupted aortic arch underwent staged repair of aorta and other cardiac lesions. Simultaneous pulmonary artery banding was performed in six of 8 patients with ventricular septal defect (VSD) and in all of seven patients with complex cardiac lesions. With first operation, there were no operative deaths and two late deaths. Eight of 14 survivors underwent total correction of associated lesions at three to 17 months after initial operation. VSD was closed in five patients with one operative death. One patient required pulmonary artery debanding alone because of decrease of VSD size. The Damus-Kaye-Stansel operation was performed successfully in one patient with Taussig-Bing anomaly and the Jatene operation was done in one with transposition of the great arteries. Based on these results, we prefer staged repair with pulmonary artery banding for coarctation or interruption of the aorta associated with complex cardiac lesions.