Metabolic acidosis in the alcoholic: A pathophysiologic approach

The purpose of this paper is to review the acid-base abnormalities in patients presenting with metabolic acidosis due to acute ethanol ingestion and to review the theoretical constraints on ethanol metabolism in the liver. Alcohol-induced acidosis is a mixed acid-base disturbance. Metabolic acidosis is due to lactic acidosis, ketoacidosis and acetic acidosis but the degree of each varies from patient to patient. Metabolic alkalosis is frequently present due to ethanol-induced vomiting. However, it could be overlooked because of an indirect loss of sodium bicarbonate (as sodium B-hydroxybutyrate in the urine). Nevertheless, the accompanying reduction in ECF volume may play an important role in the pathogenesis of alcoholic acidosis because it could lead to a relative insulin deficiency. Treatment of alcohol acidosis should include sodium, chloride, potassium, phosphorus, magnesium and thiamine replacements slong with attention to concomitant clinical problems. Unless hypoglycemia is present, glucose need not be given immediately. We feel that insulin should be withheld unless life-threatening acidemia is present or expected. Lastly, alcohol need not be detected on admission to make the diagnosis of this metabolic disturbance. However, when present, it could contribute directly to the lactic, acetic and B-hydroxybutyric acidoses. With respect to the theoretical constraints on ethanol metabolism, it appears that “overproduction” of NADH in the liver is best averted by converting ethanol to B-hydroxybutyric acid.     

Blood pressure control in hypertensive patients with stable coronary heart disease

OBJECTIVE: To evaluate systolic blood pressure (SBP) control in hypertensive patients with a stable coronary heart disease (CHD) in general practice in France. METHODS: A survey was conducted in a sample of 206 general practitionners (GP) representative of the French medical population, in 2003 [LHYCORNE survey]. Each GP had to include 3 hypertensive patients, >18 years old, BP > or = 140/90 mmHg and/or treated for hypertension, and with evidence of CHD documented by myocardial infarction (MI) or angina pectoris (AP) [diagnosis previously established by a cardiologist]. Three office BP measurements were performed, the last two recorded. BP levels were considered as controlled by treatement if they were < 140/90 mmHg. RESULTS: 595 patients were included, 75% men mean age 66 years, 25% women mean age 73 years. All patients had a CHD: MI 46%, AP 54%; 533 (90%) had more than 2 cardiovascular risk factors: hyperlipidemia (411; 69%), smokers (375; 63%), diabetes (158; 27%). Mean BP was 140.7 +/- 14/80.8 +/- 9.7 mmHg; 553 (93%) of these hypertensive patients were treated, and 239 (40%) were considered as having a controlled SBP at the treshold of 140 mmHg: 47% in patients with previous MI and 38% with AP (p < 0.001). Diastolic BP (DBP) was <90 mmHg in 480 (81%) and pulse pressure was >65 mmHg in 202 (34%); 313 (53%) patients received a combination of three drugs or more; 354 (60%) had a beta-blocker, 260 (44%) a calcium channel blocker, 237 (40%) an ACE inhibitor, 287 (48%) other antihypertensive drugs (246 diuretics, 41%); 502 (84%) received antiplatelet therapy, 403 (68%) statins. CONCLUSION: This survey shows that systolic BP is not at goal in 6/10 hypertensive patients with stable CHD suggesting there is a place for a more effective combination therapy according to evidence-based medicine.     

Primärversorgung penetrierender Verletzungen

Blast injuries may result from a variety of causes but the biomechanical impact and pathophysiological consequences do not differ between domestic or industrial accidents or even terrorist attacks. However, this differentiation relevantly affects the tactical procedures of the rescue teams. Focusing on further detonations, top priority is given to the personal safety of all rescue workers. The rareness of blast injuries in a civilian setting results in a lack of experience on the one hand but on the other hand the complexity of blast injuries to the human body places high demands on the knowledge and skills of the entire rescue team for competent treatment. The purpose of this article is to explain the physicochemical principles of explosions and to convey tactical and medical knowledge to emergency medical services.     

Prospectively measured 10-year changes in health-related quality of life and comparison with cross-sectional estimates in a population-based cohort of adult women and men

Purpose

To prospectively assess changes in health-related quality of life (HRQOL) over 10 years, by age and sex, and to compare measured within-person change to estimates of change based on cross-sectional data.

Methods

Participants in the Canadian Multicentre Osteoporosis Study completed the 36-item short form (SF-36) in 1995/1997 and 2005/2007. Mean within-person changes for domain and summary components were calculated for men and women separately, stratified by 10-year age groups. Projected changes based on published age- and sex-stratified cross-sectional data were also calculated. Mean differences between the two methods were then estimated, along with the 95 % credible intervals of the differences.

Results

Data were available for 5,569/9,423 (59.1 %) of the original cohort. Prospectively collected 10-year changes suggested that the four physically oriented domains declined in all but the youngest group of men and women, with declines in the elderly men exceeding 25 points. The four mentally oriented domains tended to improve over time, only showing substantial declines in vitality and role emotional in older women, and all four domains in older men. Cross-sectional estimates identified a similar pattern of change but with a smaller magnitude, particularly in men. Correspondence between the two methods was generally high.

Conclusions

Changes in HRQOL may be minimal over much of the life span, but physically oriented HRQOL can decline substantially after middle age. Although clinically relevant declines were more evident in prospectively collected data, differences in 10-year age increments of cross-sectional data may be a reasonable proxy for longitudinal changes, at least in those under 65 years of age. Results provide additional insight into the natural progression of HRQOL in the general population.     

Design of ternary additive for organic photovoltaics: a cautionary tale

Silicon phthalocyanines as ternary additives are a promising way to increase the performance of organic photovoltaics. The miscibility of the additive and the donor polymer plays a significant role in the enhancement of the device performance, therefore, ternary additives can be designed to better interact with the conjugated polymer. We synthesized N-9′-heptadecanyl-2,7-carbazole functionalized SiPc ((CBzPho)₂-SiPc), a ternary additive with increased miscibility in poly[N-90-heptadecanyl-2,7-carbazole-alt-5,5-(4′,7′-di-2-thienyl-2′,1′,3′-benzothiadiazole)] (PCDTBT). The resulting additive was included into PCDTBT and [6,6]-phenyl C₇₁ butyric acid methyl ester as bulk (PC₇₁BM) heterojunction OPV devices as a ternary additive. While the (CBzPho)₂-SiPc demonstrated strong EQE >30% contribution in the range of 650–730 nm, the overall performance was reduced because (CBzPho)₂-SiPc acted as a hole trap due to its high-lying HOMO energy level. This study demonstrates the importance of the solubility, miscibility, and energy level engineering of the ternary additive when designing organic photovoltaic devices.

Silicon phthalocyanines with carbazole axial functional groups were synthesized to improve the miscibility in PCDTBT and for use as ternary additives in organic photovoltaics.     

EczemaPred: A computational framework for personalised prediction of eczema severity dynamics

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease leading to substantial quality of life impairment with heterogeneous treatment responses. People with AD would benefit from personalised treatment strategies, whose design requires predicting how AD severity evolves for each individual.ObjectiveThis study aims to develop a computational framework for personalised prediction of AD severity dynamics.MethodsWe introduced EczemaPred, a computational framework to predict patient‐dependent dynamic evolution of AD severity using Bayesian state‐space models that describe latent dynamics of AD severity items and how they are measured. We used EczemaPred to predict the dynamic evolution of validated patient‐oriented scoring atopic dermatitis (PO‐SCORAD) by combining predictions from the models for the nine severity items of PO‐SCORAD (six intensity signs, extent of eczema, and two subjective symptoms). We validated this approach using longitudinal data from two independent studies: a published clinical study in which PO‐SCORAD was measured twice weekly for 347 AD patients over 17 weeks, and another one in which PO‐SCORAD was recorded daily by 16 AD patients for 12 weeks.ResultsEczemaPred achieved good performance for personalised predictions of PO‐SCORAD and its severity items daily to weekly. EczemaPred outperformed standard time‐series forecasting models such as a mixed effect autoregressive model. The uncertainty in predicting PO‐SCORAD was mainly attributed to that in predicting intensity signs (75% of the overall uncertainty).ConclusionsEczemaPred serves as a computational framework to make a personalised prediction of AD severity dynamics relevant to clinical practice. EczemaPred is available as an R package.     

Human Brain Organoids as Models for Central Nervous System Viral Infection

Pathogenesis of viral infections of the central nervous system (CNS) is poorly understood, and this is partly due to the limitations of currently used preclinical models. Brain organoid models can overcome some of these limitations, as they are generated from human derived stem cells, differentiated in three dimensions (3D), and can mimic human neurodevelopmental characteristics. Therefore, brain organoids have been increasingly used as brain models in research on various viruses, such as Zika virus, severe acute respiratory syndrome coronavirus 2, human cytomegalovirus, and herpes simplex virus. Brain organoids allow for the study of viral tropism, the effect of infection on organoid function, size, and cytoarchitecture, as well as innate immune response; therefore, they provide valuable insight into the pathogenesis of neurotropic viral infections and testing of antivirals in a physiological model. In this review, we summarize the results of studies on viral CNS infection in brain organoids, and we demonstrate the broad application and benefits of using a human 3D model in virology research. At the same time, we describe the limitations of the studies in brain organoids, such as the heterogeneity in organoid generation protocols and age at infection, which result in differences in results between studies, as well as the lack of microglia and a blood brain barrier.     

Meta-analyses of therapies for postmenopausal osteoporosis. VIII: Meta-analysis of the efficacy of vitamin D treatment in preventing osteoporosis in postmenopausal women

OBJECTIVE: To review the effect of vitamin D on bone density and fractures in postmenopausal women. DATA SOURCE: We searched MEDLINE and EMBASE from 1966 to 1999 and examined citations of relevant articles and proceedings of international meetings. We contacted osteoporosis investigators and primary authors to identify additional studies and to obtain unpublished data. STUDY SELECTION: We included 25 trials that randomized women to standard or hydroxylated vitamin D with or without calcium supplementation or a control and measured bone density or fracture incidence for at least 1 yr. DATA EXTRACTION: For each trial, three independent reviewers assessed the methodological quality and abstracted data. DATA SYNTHESIS: Vitamin D reduced the incidence of vertebral fractures [relative risk (RR) 0.63, 95% confidence interval (CI) 0.45-0.88, P < 0.01) and showed a trend toward reduced incidence of nonvertebral fractures (RR 0.77, 95% CI 0.57-1.04, P = 0.09). Most patients in the trials that evaluated vertebral fractures received hydroxylated vitamin D, and most patients in the trials that evaluated nonvertebral fractures received standard vitamin D. Hydroxylated vitamin D had a consistently larger impact on bone density than did standard vitamin D. For instance, total body differences in percentage change between hydroxylated vitamin D and control were 2.06 (0.72, 3.40) and 0.40 (-0.25, 1.06) for standard vitamin D. At the lumbar spine and forearm sites, hydroxylated vitamin D doses above 50 microg yield larger effects than lower doses. Vitamin D resulted in an increased risk of discontinuing medication in comparison to control as a result of either symptomatic adverse effects or abnormal laboratory results (RR 1.37, 95% CI 1.01-1.88), an effect that was similar in trials of standard and hydroxylated vitamin D. CONCLUSIONS: Vitamin D decreases vertebral fractures and may decrease nonvertebral fractures. The available data are uninformative regarding the relative effects of standard and hydroxylated vitamin D.