Age differences in the association of comorbid burden with adverse outcomes in SARS-CoV-2.

BACKGROUND: Older age and comorbid burden are both associated with adverse outcomes in SARS-CoV-2, but it is not known whether the association between comorbid burden and adverse outcomes differs in older and younger adults. OBJECTIVE: To compare the relationship between comorbid burden and adverse outcomes in adults with SARS-CoV-2 of different ages (18-64, 65-79 and ≥ 80 years). DESIGN, SETTING, AND PARTICIPANTS: Observational longitudinal cohort study of 170,528 patients who tested positive for SARS-CoV-2 in the US Department of Veterans Affairs (VA) Health Care System between 2/28/20 and 12/31/2020 who were followed through 01/31/2021. MEASUREMENTS: Charlson Comorbidity Index (CCI); Incidence of hospitalization, intensive care unit (ICU) admission, mechanical ventilation, and death within 30 days of a positive SARS-CoV-2 test. RESULTS: The cumulative 30-day incidence of death was 0.8% in cohort members < 65 years, 7.1% in those aged 65-79 years and 20.6% in those aged ≥80 years. The respective 30-day incidences of hospitalization were 8.2, 21.7 and 29.5%, of ICU admission were 2.7, 8.6, and 11% and of mechanical ventilation were 1, 3.9 and 3.2%. Median CCI (interquartile range) ranged from 0.0 (0.0, 2.0) in the youngest, to 4 (2.0, 7.0) in the oldest age group. The adjusted association of CCI with all outcomes was attenuated at older ages such that the threshold level of CCI above which the risk for each outcome exceeded the reference group (1st quartile) was lower in younger than in older cohort members (p < 0.001 for all age group interactions). LIMITATIONS: The CCI is calculated based on diagnostic codes, which may not provide an accurate assessment of comorbid burden. CONCLUSIONS: Age differences in the distribution and prognostic significance of overall comorbid burden could inform clinical management, vaccination prioritization and population health during the pandemic and argue for more work to understand the role of age and comorbidity in shaping the care of hospitalized patients with SARS-CoV-2.

Chaperones and intimate physical examinations: what do male and female patients want?

INTRODUCTION: Many studies of patients' perception of a medical chaperone have focused on female patients; that of male patients are less well studied. Moreover, previous studies were largely based on patient populations in English-speaking countries. Therefore, this study was conducted to investigate the perception and attitude of male and female Chinese patients to the presence of a chaperone during an intimate physical examination. METHODS: A cross-sectional guided questionnaire survey was conducted on a convenient sample of 150 patients at a public teaching hospital in Hong Kong. RESULTS: Over 90% of the participants considered the presence of a chaperone appropriate during intimate physical examination, and 84% felt that doctors, irrespective of gender, should always request the presence of a chaperone. The most commonly cited reasons included the availability of an objective account should any legal issue arise, protection against sexual harassment, and to provide psychological support. This contrasted with the experience of those who had previously undergone an intimate physical examination of whom only 72.6% of women and 35.7% of men had reportedly been chaperoned. Among female participants, 75.0% preferred to be chaperoned during an intimate physical examination by a male doctor, and 28.6% would still prefer to be chaperoned when being examined by a female doctor. Among male participants, over 50% indicated no specific preference but a substantial minority reported a preference for chaperoned examination (21.2% for male doctor and 25.8% for female doctor). CONCLUSIONS: Patients in Hong Kong have a high degree of acceptance and expectations about the role of a medical chaperone. Both female and male patients prefer such practice regardless of physician gender. Doctors are strongly encouraged to discuss the issue openly with their patients before they conduct any intimate physical examination.

Stress responses to short-term intensified and reduced training in competitive weightlifters.

We sought to identify and evaluate the tolerance to, and consequences of, short-term variations in training load in competitive weightlifters. Seven international-level lifters performed 1 week of initial training followed by 2 weeks of intensified (INT: +100%, 36.5 ± 11.3 × 10(3) kg/week) and 1 week of subsequently reduced (RED: -25%) training within their annual program. After INT, but not RED, 90 min of weightlifting increased mRNA levels of chemokine (C-C motif) ligand 4 (CCL4), chemokine (C-X-C motif) receptor 4 (CXCR4) and cellular stress-associated DNA-damage-inducible transcript 4 (DDIT4) in peripheral blood mononuclear cells by 40-240%. Resting- and weightlifting-induced changes in plasma protein carbonyls, indicative of oxidative stress, but not pro-inflammatory CCL4 concentrations differed between INT and RED. Symptoms of stress (Daily Analysis of Life Demands of Athletes questionnaire) were reported as worse than normal more frequently during INT and RED than initial training. Global (negative) mood state increased during INT and declined during RED. Maximal snatch (-4.3 ± 3.7%) and vertical jump (-7.2 ± 6.5%), but not clean and jerk, were reduced after INT and restored after RED. Chemokine signaling may thus be part of the stress response to intense weightlifting and short-term reductions in training load support recovery from periodic INT training in weightlifters.

Multifocal cutaneous metastases from squamous cell carcinoma of hard palate.

Distant metastases from oral squamous cell carcinoma are unusual, but generally occur in lungs, bone, and liver. Cutaneous metastasis is extremely rare, and it often reflects an advanced stage with sinister prognosis. The authors report an 81-year-old male patient with multifocal cutaneous metastases from a recurrent squamous cell carcinoma of the hard palate 5 months after primary treatment.

Polymorphic variation in surfactant protein B is associated with COPD exacerbations.

Exacerbations of chronic obstructive pulmonary disease (COPD) reduce quality of life and increase mortality. Genetic variation might explain the substantial variability seen in exacerbation frequency among COPD subjects with similar lung function. Polymorphisms in five candidate genes, previously associated with COPD susceptibility, were analysed in order to determine whether they demonstrated association with COPD exacerbations. A total of 88 single nucleotide polymorphisms (SNPs) in the genes microsomal epoxide hydrolase (EPHX1), transforming growth factor, beta-1 (TGFB1), serpin peptidase inhibitor, clade E (nexin, plasminogen activator inhibitor type 1), member 2 (SERPINE2), glutathione S-transferase pi (GSTP1) and surfactant protein B (SFTPB) were genotyped in 389 non-Hispanic white participants in the National Emphysema Treatment Trial. Exacerbations were defined as COPD-related emergency room visits or hospitalisations using the Centers for Medicare and Medicaid Services claims data. One or more exacerbations were experienced by 216 (56%) subjects during the study period. An SFTPB promoter polymorphism, rs3024791, was associated with COPD exacerbations. Logistic regression models, analysing a binary outcome of presence or absence of exacerbations, confirmed the association of rs3024791 with COPD exacerbations. Negative binomial regression models demonstrated association of multiple SFTPB SNPs (rs2118177, rs2304566, rs1130866 and rs3024791) with exacerbation rates. Polymorphisms in EPHX1, GSTP1, TGFB1 and SERPINE2 did not demonstrate association with COPD exacerbations. In conclusion, genetic variation in surfactant protein B is associated with chronic obstructive pulmonary disease susceptibility and exacerbation frequency.

Comparison of osteogenesis of human embryonic stem cells within 2D and 3D culture systems.

The objective of this study was to compare the osteogenic potential of human embryonic stem cells (hESCs) within two- and three-dimensional (2D and 3D) culture systems. hESCs of the H1 line (Wicell Inc., Madison, Wisc., USA) were induced to form embryoid bodies (EBs) through 5 days of suspension culture within non-adherent culture dishes. Following enzymatic dissociation, the EB-derived single cells were seeded on either novel 3D porous PLGA scaffolds or 2D culture dishes with the same total cell number. Osteogenic differentiation was induced through culture media supplemented with dexamethasone, L-ascorbic acid and beta-glycerophosphate. After 3 weeks of in vitro culture, quantitative and qualitative assays of osteogenic differentiation were conducted. Osteocalcin secretion and alkaline phosphatase (AP) activities were detected at significantly higher levels within 3D culture compared with the 2D system. Subsequently, the cell-scaffold constructs were implanted in iliac crest defects of immunosuppressed rabbits. After 4 weeks, the constructs were subsequently explanted and characterized by histology and X-ray analysis. Formation of new bone was detected within and around the implanted scaffolds. The results demonstrate that the osteogenic differentiation of human embryonic stem cells is enhanced in a 3D culture system compared to a 2D culture environment. Upon implantation in situ, the differentiating human embryonic stem cells can contribute positively to the repair and regeneration of bone defects.

Radial free flaps using loupe magnification: audit of 97 cases of orofacial reconstruction.

We present a retrospective audit of radial fasciocutaneous vascularised free flaps performed over a decade. These have all been done with binocular loupe magnification, allowing comparison of free flap success with conventional microscope vessel anastomosis. The results are similar to other reported series.

Urgent laparotomy versus emergency craniotomy for multiple trauma with head injury patients.

In blunt multiple trauma (MT) with head injury (HI) patients, it is difficult to decide whether to proceed with immediate laparotomy or craniotomy. In August 1989, abdominal ultrasonography (US) using a simple US scoring system was introduced for MT and HI patients as an initial rapid screening procedure. In MT and HI patients with a US score > or = 3 (n = 14), urgent laparotomy was the procedure of first choice. However, immediate head CT scan, then emergency craniotomy, may be justified in hemodynamically stable MT and HI patients with a US score < 3 (n = 98). Appropriate decision making can be applied to decide which procedure is most exigent.

[The interaction of lipoic acid and its metabolites with aspartate and alanine aminotransferases in a multienzyme complex from rat liver and brain mitochondria]. / Vzaiemodiia lipoievoï kysloty ta ïï metabolitiv z aspartat- i alaninaminotransferazoiu u mul'tienzymnomu kompleksi mitokhondrii pechinky i mozku shchuriv.

It is shown that lipoic acid and its metabolites--lipoamide and 4,6-dithiohexanoic acid can interact and inhibit the mitochondrial aspartate- and alanine-aminotransferase activities. This effect is much more pronounced in the case of multienzyme complexes--metabolon.

Genetic transformation with cell wall-associated deoxyribonucleic acid in Bacillus subtilis.

Cell walls from bacillus subtilis 168 were prepared by conventional methods and found to contain deoxyribonucleic acid (DNA). In transformation assays, after autolysis, it was found that two major regions of the chromosome were selectively enriched in the wall preparations. One region clustered around the replication origin and is represented by the markers purA16, ts8132, thiC5, sacA321, and hisA1. The other region included the replication terminus with representative loci metB10, citK5, gltA292, and pyrA1. All other (internal) loci which were examined showed no statistical enrichment. The two areas of enrichment were similar to but more extensive than those reported for membrane-DNA complexes. The wall preparations also contained protein and lipid, indicating a possible membrane involvement. Analyses of the cell walls revealed that the fatty acid composition of the membrane component was not typical of the for B. subtilis protoplast membranes or for lipoteichoic acids. In addition, radioiodination of cell wall autolysates, followed by gel electrophoresis and autoradiography, demonstrated the presence of proteins not readily detectable in bulk protoplast membranes or on the surfaces of intact cells. These data suggest that a unique component of the membrane and regions of the B. subtilis genome involved in DNA replication events are tightly associated with cell walls. The binding of DNA-membrane complexes to the "rigid" cell wall and the replication of the wall could be a mechanism by which the segregation of growing chromosomes occurs.

Release of membrane constituents following polyethylene glycol treatment of HEp-2 cells.

HEp-2 cell monolayers were treated with 40% polyethylene glycol for 5 min which resulted in fusion during the subsequent incubation period. A loss of cell membrane components was detected in the polyethylene glycol-treated as well as phosphate buffer/saline-treated control cells, however the polyethylene glycol-treated cells released nearly twice the amount of [14C]acetate-labeled material and [3H]glycerol-labeled lipids into culture fluids than the control cells. It was further detected that the polyethylene glycol-treated cells released only approximately half the amount of protein, glycoprotein, and glycolipid as the control cells. These results suggest that polyethylene glycol exerts a differential mode of action against cell surface components and causes the treated cells to release membrane components rich in lipids but relatively low in protein and carbohydrate-containing components.

Cell wall protein in Bacillus subtilis.

The cell wall of Bacillus subtilis 168 contains protein that is refractory to removal by salts, detergents, and denaturants.

The cause and treatment of postvagotomy diarrhoea.

Six patients with watery postvagotomy diarrhoea and 4 patients with intractable diabetic diarrhoea were treated with cholestyramine. The diarrhoea responded completely to therapy, during which the stool content of water, sodium, postassium and magnesium fell. Two of the patients, while receiving cholestyramine, had a rise in faecal fat, but this was not accompanied by diarrhoea, the stools being well formed. Evidence is presented which suggests that the mechanism of diarrhoea is similar in both disorders and is due to division or neuropathy of the hepatic fibres of the vagus nerve. This results is distension of the gallbladder, contraction of which expels increased quantities of bile salts, which swamp the reabsorptive capacity of the small intestine and induce diarrhoea by direct action on the colon. If this theory is valid, cholecystectomy, by preventing large quantities of concentrated bile salts from suddenly entering the gut, may result in improvement of postvagotomy and diabetic diarrhoea.

Biosynthesis of Phospholipids and neutral lipids of monkey kidney cells (LLC-MK-2) infected with Chlamydia trachomatic strain lymphogranuloma venereum (38538).

The biosynthesis of phospho-lipids and neutral lipids in normal and monkey kidney cells infected with lymphogranuloma venereum were compared using 14C-acetate and 14-C-serine in pulse-chase experiments. Synthesis of phospholipids and nutral glycerolipids were inhibited in infected cells. Phosphatidyl ethanolamine (PE) synthesis increased while phosphatidyl choline, phosphatidyl serine and cardiolipin synthesis decreased in infected cells within 36 hr after infection. Sphingomyelin syntheisis decreased after 48 hr of infection. The synthesis of PE in the infected cell followed a similar pathway found in bacteria and could be distinguished from the normal host cell. An explanation of the parsitic requirement for lipid precursors has been proposed.