Territorywide Study of Early Coronavirus Disease Outbreak,Hong Kong,China

Initial cases of coronavirus disease in Hong Kong were imported from mainland China. A dramatic increase in case numbers was seen in February 2020. Most case-patients had no recent travel history, suggesting the presence of transmission chains in the local community. We collected demographic, clinical, and epidemiologic data from 50 patients, who accounted for 53.8% of total reported case-patients as of February 28, 2020. We performed whole-genome sequencing to determine phylogenetic relationship and transmission dynamics of severe acute respiratory syndrome coronavirus 2 infections. By using phylogenetic analysis, we attributed the community outbreak to 2 lineages; 1 harbored a common mutation, Orf3a-G251V, and accounted for 88.0% of the cases in our study. The estimated time to the most recent common ancestor of local coronavirus disease outbreak was December 24, 2019, with an evolutionary rate of 3.04 × 10⁻³ substitutions/site/year. The reproduction number was 1.84, indicating ongoing community spread.     

Best Performance Parameters of HR-pQCT to Predict Fragility Fracture: Systematic Review and Meta-Analysis

Osteoporosis is a systemic skeletal disease characterized by low bone mass and bone structural deterioration that may result in fragility fractures. Use of bone imaging modalities to accurately predict fragility fractures is always an important issue, yet the current gold standard of dual-energy X-ray absorptiometry (DXA) for diagnosis of osteoporosis cannot fully satisfy this purpose. The latest high-resolution peripheral quantitative computed tomography (HR-pQCT) is a three-dimensional (3D) imaging device to measure not only volumetric bone density, but also the bone microarchitecture in a noninvasive manner that may provide a better fracture prediction power. This systematic review and meta-analysis was designed to investigate which HR-pQCT parameters at the distal radius and/or distal tibia could best predict fragility fractures. A systematic literature search was conducted in Embase, PubMed, and Web of Science with relevant keywords by two independent reviewers. Original clinical studies using HR-pQCT to predict fragility fractures with available full text in English were included. Information was extracted from the included studies for further review. In total, 25 articles were included for the systematic review, and 16 articles for meta-analysis. HR-pQCT was shown to significantly predict incident fractures and/or major osteoporotic fractures (MOFs). Of all the HR-pQCT parameters, our meta-analysis revealed that cortical volumetric bone mineral density (Ct.vBMD), trabecular thickness (Tb.Th), and stiffness were better predictors. Meanwhile, HR-pQCT parameters indicated better performance in predicting MOFs than incident fractures. Between the two standard measurement sites of HR-pQCT, the non-weight-bearing distal radius was a more preferable site than distal tibia for fracture prediction. Furthermore, most of the included studies were white-based, whereas very few studies were from Asia or South America. These regions should build up their densitometric databases and conduct related prediction studies. It is expected that HR-pQCT can be used widely for the diagnosis of osteoporosis and prediction of future fragility fractures. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).     

Familial Transmission of Alcohol Use Norms and Expectancies and Reported Alcohol Use

Members of 183 families (biological parents and one adult offspring) completed questionnaires on their quantity and frequency of alcohol use, what they would consider a "normal" quantity-frequency of alcohol use, "problem" quantity-frequency of use, flushing after alcohol use, and other expected physiological and subjective responses to alcohol. Within individuals, own quantity-frequency of alcohol use was moderately negatively correlated with flushing after one drink or less ("fast flushing"), but more highly positively correlated with judged normal alcohol use and with expected subjective effects. Spouse resemblances were low for quantity-frequency of alcohol use and flushing, but high for alcohol use norms and expected physiological and subjective responses. Parent-offspring resemblances were low to moderate for own alcohol use and flushing, but moderate to high for expected physiological and subjective effects. These results were discussed in terms of the effects of genetically transmitted flushing after alcohol use and culturally transmitted alcohol norms and expectations on alcohol use.     

GABA(A) receptors mediate inhibition of T cell responses

We describe the presence of functional GABA(A) receptors on T cells. GABA inhibited anti-CD3 and antigen-specific T cell proliferation in vitro in a dose-dependent manner that was 1) mimicked by the GABA(A) receptor agonist muscimol (but not the GABA(B) receptor agonist baclofen), 2) blocked by GABA(A) receptor antagonists and a GABA(A) receptor Cl- channel blocker (picrotoxin) and 3) enhanced by pentobarbital. These data suggest that GABA(A) receptors mediate this immune inhibition and that these receptors can be modulated in a similar fashion to their neuronal counterparts. Finally, GABA inhibited DTH responses in vivo. Thus, pharmacological modulation of GABA(A) receptors may provide new approaches to modulate T cell responses in inflammation and autoimmune disease.     

The trough: peak ratio and the normalization of blood pressure profiles

Experts from the Food and Drug Administration (FDA) of the USA have assumed that hypertensive patients are likely to achieve greatest benefit from therapy in which the antihypertensive effects do not vary excessively during the course of the day. They suggested that the ratio of the minimal (trough) effect to the maximal (peak) effect of the drug should be no lower than 0.5. The concept of the trough: peak ratio (TPR) raises many practical problems. Using actual data, the effect of a drug often shows erratic fluctuations with several local minima and maxima. Mean blood pressure levels for several hours have been used to estimate the trough and peak effects. Blood pressure averages over 4 h may e a good choice, because blood pressures measured 4 h apart are not correlated. The statistical distribution of the TPR is not Gaussian. Negative and very low or positive and very high individual ratios are frequently observed. Therefore, the individual TPR is of questionable clinical value, except when the ratio is applied for responders only. The TPR can be calculated for a sample. In that case, the bootstrap method can be used to estimate the error of the TPR. Most important is the question of why the TPR should be higher than 0.5. We introduced the concept of 'normalization of the blood pressure profile', namely 'reducing the blood pressure profiles in hypertensives to match those profiles in normotensives'. This concept leads very naturally to the TPR and justifies the lower limit of 0.5 for the TPR.     

Cholesterol and other cardiovascular risk factors in a working population in Ile-De-France (France): First results of the PCV-METRA study

In 1989, the French PCV-METRA Group (PCV-METRA = Prévention Cardio-Vasculaire en Médecine du Travail) started a large prospective survey of cardiovascular (CDV) morbidity and mortality and of CVD risk factors, especially cholesterol, in a working population in Ile-de-France, a region including Paris. This report presents the first results of this study, based on a sample of 5758 men and 2603 women, aged 18–65 years. The variables examined included the levels of total cholesterol (TC), High-density-lipooprotein cholesterol (HDL-C), low-density-lipoprotein cholesterol (LDL-C), and the other major CVD risk factors (smoking, sedentary way of life, hypertension, hypercholesterolemia, use of oral contraceptives and familial history of CVD risks). TC and LDL-C significantly increased with age. The changes with age were significantly different in men and women. The levels were similar in both sexes at less than 30 yrs, increased sharply for men after age 30 and were significantly higher in men than in women from 30 to 55 yrs. Beyond 55 yrs, no difference was obserbed between the two sexes. In contrast, HDL-C was higher in women at all age ranges. In the total sample, 35% of men and 21% of women were hypercholesterolemic (TC 2.4 g/ L). Our observations fully confirm and refine previous findings in the US and in other European countries. In addition, a substantial set of data on CVD risk factors for the working population in France, especially for female subjects for whom data are scanty, is now available.Corresponding author.     

Factors involved in the differential response to ethanol,barbital and pentobarbital in rats selectively bred for ethanol sensitivity

Two lines of rats, least affected (LA) and most affected (MA), had been selectively bred for their differential sensitivity to ethanol. Both males and females of the LA strain were observed to be less sensitive than their MA counterparts to the acute hypnotic and motor-impairing effects of ethanol. However, a lower ethanol metabolic rate of the MA males suggests that both CNS and metabolic factors contribute to their enhanced sensitivity to ethanol. By contrast, no differences were observed between the LA and MA males with respect to the hypnotic and subhypnotic effects of pentobarbital or to the clearance of this drug. MA females were more sensitive only to the hypnotic effects of pentobarbital, probably because of a smaller apparent volume of distribution. No strain difference was observed in the hypnotic effect or clearance of barbital. These observations suggest that, in spite of a differential sensitivity to ethanol, the LA and MA lines do not differ in their response to the barbiturates tested.     

Implantation of a composite bifurcated cryopreserved aorto-iliac-femoral homograft in a patient with Candida albicans endocarditis

A 35 year old woman, cocaine addict, suffered Candida albicans aortic valve endocarditis complicated with embolisation of infected vegetations in the distal abdominal aorta. She underwent successful staged aortic valve replacement followed by transaortic and transfemoral thrombectomy. One month later an arteriogram disclosed partial occlusion of the left iliac artery, bilateral aneurysmal degeneration of both iliac arteries and right iliac artery-right iliac vein fistula. She was operated again, performing re-laparotomy and re-exploration. A composite bifurcated cryopreserved homograft was implanted end-to-side between the infrarenal abdominal aorta, right external iliac artery and left common femoral artery. The right iliac artery-iliac vein fistula was obliterated with suture. The patient had an uneventful recovery but a relapsing arterio-venous fistula was diagnosed by arteriography. Three months later she underwent percutaneous transluminal closure of the reopened fistula. At present, 17 months after the implantation of the homograft, the patient is symptom-free, on antifungal agents and with arteriographic and clinical evidence of a well-functioning arterial homograft.