A point-prevalence study of body mass indices in HIV-positive and HIV-negative patients admitted to hospital with COVID-19 in South Africa.

Background: Obesity is now well recognised as a risk factor for severe COVID-19, but the true prevalence of obesity in hospitalised adults with COVID-19 remains unclear because formal body mass indices (BMIs) are not routinely measured on admission. Objectives: To describe the true prevalence of obesity measured by the BMI, and associated comorbidities, in patients hospitalised with severe COVID-19, including people with HIV (PWH). Methods: We conducted a point-prevalence study of measured BMI in consecutive patients with severe COVID-19 admitted to the medical COVID-19 wards in a tertiary academic hospital in Cape Town, South Africa (SA). Patients were enrolled over a 2-week period during the peak of the first COVID-19 wave in SA. Results: We were able to measure the BMI in 122 of the 146 patients admitted during the study period. The prevalence of HIV was 20% (n=24/122). Most of the participants were overweight or obese (n=104; 85%), and 84 (68.9%) met criteria for obesity. The mean (standard deviation) BMI was 33 (7.5), and 34.5 (9.1) in PWH. Of PWH, 83% (n=20/24) were overweight or obese and 75% (n=18) met criteria for obesity. Multimorbidity was present in 22 (92%) of PWH. Conclusion: We found that most patients, including PWH, met criteria for being overweight or obese. The high prevalence of obesity in PWH and severe COVID-19 reinforces the need for targeted management of non-communicable diseases, including obesity, in PWH. Study synopsis: What the study adds. We found that the true prevalence of obesity, including in people with HIV (PWH), measured with the formal body mass index in hospitalised patients with severe COVID-19 was much higher than reported previously.Multimorbidity was present in over half of all patients, and in 92% of PWH. Implications of the findings. Urgent public health measures are required to tackle the rise in obesity, including in low- and middle-income countries.HIV care must integrate management of non-communicable diseases, including obesity.The pathogenic mechanism of the link between obesity and severe COVID-19 needs further research.

The optimal management of the patient with COVID-19 pneumonia: HFNC, NIV/CPAP or mechanical ventilation?

The recent pandemic has seen unprecedented demand for respiratory support of patients with COVID-19 pneumonia, stretching services and clinicians. Yet despite the global numbers of patients treated, guidance is not clear on the correct choice of modality or the timing of escalation of therapy for an individual patient. This narrative review assesses the available literature on the best use of different modalities of respiratory support for an individual patient, and discusses benefits and risks of each, coupled with practical advice to improve outcomes. On current data, in an ideal context, it appears that as disease severity worsens, conventional oxygen therapy is not sufficient alone. In more severe disease, i.e. PaO2/FiO2 ratios below approximately 200, helmet-CPAP (continuous positive airway pressure) (although not widely available) may be superior to high-flow nasal cannula (HFNC) therapy or facemask non-invasive ventilation (NIV)/CPAP, and that facemask NIV/CPAP may be superior to HFNC, but with noted important complications, including risk of pneumothoraces. In an ideal context, invasive mechanical ventilation should not be delayed where indicated and available. Vitally, the choice of respiratory support should not be prescriptive but contextualised to each setting, as supply and demand of resources vary markedly between institutions. Over time, institutions should develop clear policies to guide clinicians before demand exceeds supply, and should frequently review best practice as evidence matures.

Determination of depth-dependent diffraction data: a new approach.

A direct method for determining powder diffraction data at specific depths from angle-dependent diffraction data is described. The method is non-destructive and only traditional data collections, where the angle of incidence is varied, are required. These angle-dependent spectra are transformed to give diffraction data arising from different depths, which may then be exploited using any conventional method. This is a novel approach as traditional methods are forced to tolerate the inherent depth averaging of grazing-angle diffraction, or only examine specific structural characteristics. In order to obtain depth-dependent X-ray diffraction data, a Fredholm integral equation of the first kind is solved using regularization techniques. The method has been validated by the generation of pseudo-experimental data having known depth profiles and solving the Fredholm integral equation to recover the solution. The method has also been applied to experimental data from a number of thin film systems.

Hydroxylapatite chromatography.

Hydroxylapatite (also called hydroxyapatite), a form of calcium phosphate, can be used as a matrix for the chromatography of both proteins and nucleic acids. Protocols are provided for both standard low-pressure chromatography of a protein mixture using a hydroxylapatite column prepared in the laboratory, and an HPLC method, applicable to proteins and nucleic acids, that uses a commercially available column. Alternate protocols describe column chromatography using a step gradient or batch binding and step-gradient elution.

Acceleration perturbations of daily living. A comparison to 'whiplash'.

STUDY DESIGN: This study measured repeated human head accelerations (g) during daily activities. OBJECTIVES: Perturbations of daily living were compared to similar data from low velocity rear-end motor vehicle accidents. SUMMARY OF BACKGROUND DATA: Past assumptions suggest that motor vehicle accident severity does not correlate with the degree of sustained injury. Early engineering studies indicated that occupant disturbance in a low velocity motor vehicle accident is minor. METHODS: Eight volunteers were perturbed with 13 daily activities. Helmets on the heads of volunteers were instrumented with tri-planar accelerometers with output sampling of 500 Hz, sensitivity of 0.02 g, and a range of +/- 20 g. RESULTS: There was wide inter-subject response for various perturbations. Plopping backward into a chair caused maximum peak acceleration horizontally at 5.6 g and vertically at 8.5 g, with force vector of 10.1 g at 54.9 degrees. Mean impulse duration was 0.19 sec. There was no hint of injury in any subject. CONCLUSIONS: Perturbations of daily living compared similarly to the jostling expected in low velocity "whiplash"-type motor vehicle accidents.

Assay of HIV-1 proteinase: a colorimetric method using small peptide substrates.

A colorimetric assay for HIV proteinase using small protected peptide substrates is described. Substrates are cleaved to release N-terminal prolyl peptides which react with isatin to form a blue product which is measured spectrophotometrically. The assay is suitable for use with pure enzyme or crude extracts derived from genetically engineered Escherichia coli.

Hydrolysis of synthetic chromogenic substrates by HIV-1 and HIV-2 proteinases.

Kinetic constants (Km,Kcat) are derived for the hydrolysis of a number of chromogenic peptide substrates by the aspartic proteinase from HIV-2. The effect of systematic replacement of the P2 residue on substrate hydrolysis by HIV-1 and HIV-2 proteinases is examined.

Rational design of peptide-based HIV proteinase inhibitors.

A series of peptide derivatives based on the transition-state mimetic concept has been designed that inhibit the proteinase from the human immunodeficiency virus (HIV). The more active compounds inhibit both HIV-1 and HIV-2 proteinases in the nanomolar range with little effect at 10 micromolar against the structurally related human aspartic proteinases. Proteolytic cleavage of the HIV-1 gag polyprotein (p55) to the viral structural protein p24 was inhibited in chronically infected CEM cells. Antiviral activity was observed in the nanomolar range (with one compound active below 10 nanomolar) in three different cell systems, as assessed by p24 antigen and syncytium formation. Cytotoxicity was not detected at 10 and 5 micromolar in C8166 and JM cells, respectively, indicating a high therapeutic index for this new class of HIV proteinase inhibitors.

Inhibition of the aspartic proteinase from HIV-2.

Kinetic constants were determined for the interaction of the HIV-2 aspartic proteinase with a synthetic substrate and a number of inhibitors at several pH values. Acetyl-pepstatin was more effective towards HIV-2 proteinase than the renin inhibitor, H-261; this effect is exactly the opposite from that observed previously for the proteinase from the HIV-1 AIDS virus.

Cyclohexane triones, novel membrane-active antibacterial agents.

The cyclohexane triones are a novel group of synthetic antibacterial agents that are active against gram-positive bacteria, Haemophilus influenzae, and Mycobacterium smegmatis. In general, these compounds behaved in a manner similar to that of hexachlorophene, inhibiting the transport of low-molecular-weight hydrophilic substances into bacteria. Unlike cationic detergents, such as chlorhexidine, they did not cause disruption of the bacterial cytoplasmic membrane over a short time period. The most potent antibacterial cyclohexane trione studied had a reduced ability to inhibit solute transport in comparison with certain less active analogs. Cyclohexane triones may express more than a single type of antibacterial effect.

Dietary and other characteristics relevant for coronary heart disease in men of Indian, West Indian and European descent in London.

The origins of the high standardized mortality ratio (SMR) for coronary heart disease (CHD) among Indians in Britain, and the low SMR for West Indian immigrants, have been explored by a community survey in London. Serum lipoproteins, plasma glucose, haemostatic factors and other putative risk characteristics were measured in 75 Indian, 64 European and 24 West Indian men aged 45-54 years. These represented 81% of men registered with a general practice and resident within a defined area. In 51 men, diet was assessed by 5-day weighed inventory. Plasma phospholipid fatty acids (PFA) were measured in 18 Indians and 19 Europeans with dietary records. The relatively high HDL and HDL2-cholesterol concentrations, low LDL-cholesterol concentration, reduced fat intake, increased ratio of dietary polyunsaturated/saturated fat, relatively frequent use of alcohol, and lack of obesity in West Indians accorded with their low SMR from CHD. By contrast, only the relatively low HDL and HDL2-cholesterol concentrations, infrequency of alcohol consumption, and lower proportion of PFA as n-3 fatty acids of marine origin afforded explanations for the high SMR of Indians. Hyperglycaemia appeared similarly prevalent in Indians and West Indians, but less common in Europeans. Of the haemostatic factors, West Indians had a relatively low VIIc (not statistically significant), while Indians had an increased platelet count and reduced platelet volume. Improved understanding of these ethnic differences in CHD mortality may depend upon elucidation of the contrasts in HDL-cholesterol concentration.

Heterogeneous 3H-rauwolscine binding sites in rat cortex: two alpha 2-adrenoceptor subtypes or an additional non-adrenergic interaction?

Ligand binding and isolated tissue data have provided evidence for the existence of two, tissue-specific, alpha 2-adrenoceptor subtypes in various rodent and non-rodent species. Thus it has been proposed that the complex binding of alpha 2-antagonists to rat cortical membranes is due to the presence of both subtypes in this tissue. We have previously shown that the alpha 2-antagonist 3H-rauwolscine binds to two sites on rat cortical membranes: a high affinity component characterised pharmacologically as an alpha 2-binding site, and a low affinity, spiperone-sensitive, serotonergic-like component. By the use of computerised non-linear curve-fitting, and the inclusion of (in the incubation buffer of displacement experiments) a concentration of spiperone previously shown to selectively occlude the low affinity component of the 3H-rauwolscine saturation isotherm, we have determined the rank order of affinity at each of the two sites. Whereas the rank order of affinity at the high affinity site retains the pharmacological profile of a single, monophasic alpha 2-binding site, that at the low affinity component is markedly different and is similar to that at the putative 5HT1A subtype. These data, together with the additional, functional serotonergic interactions of rauwolscine and yohimbine, indicate that there is no evidence to support the existence of heterogeneous alpha 2-binding sites, as measured by 3H-rauwolscine binding, on rat cortical membranes. Furthermore, we present evidence that the specific, low affinity serotonergic interaction of 3H-rauwolscine could be avoided by a more judicial estimation of specific binding.

Validity of calculating fatty acid intake from mixed diets.

One hundred and seventy six weighed duplicate diets were collected over 16 consecutive days from 11 subjects. Analyses of their fatty acid composition were used to asses the validity of food composition tables. Four different calculating techniques were employed. Using the published data produced correlation coefficients of 0.29 between analysed and calculated polyunsaturated/saturated fatty acid ratios, whilst the addition of new analytical data and recoding fried foods produced a correlation coefficient of 0.56. The latter method also decreased the mean difference between analysed and calculated polyunsaturated/saturated consumption, when compared with the standard procedure.

Fatty acid composition of selected foods consumed in a mixed diet study.

In a 16 day dietary survey of 11 subjects, twenty foods were consumed which contributed significantly to the fat intake of the group, but on which fatty acid data were not available. These twenty foods were sampled using the procedure described in the published food composition tables and analysed for their fatty acid composition. The sampling procedure and results of fatty acid analysis are presented.

Residual effects of zopiclone (Imovane).

A double-blind, randomized, cross-over study has been conducted with zopiclone (Imovane), a new cyclopyrrolone hypnotic in ten healthy volunteers. Hypnotic efficacy has previously been demonstrated at a dose of 7.5 mg. The present study was designed to determine the overnight residual effects of different doses of the drug ranging from 2.5 to 10 mg. Measurement of complex reaction time was used as an objective test of impairment of psychomotor function. To supplement this, the volunteers were asked to report, by means of visual analogue scales, any perceived changes in their performance in the complex reaction time test, in their mood, and in the onset and quality of sleep. Complex reaction time testing revealed no significant impairment except at 12 h after the 10 mg dose. Subjective assessments of onset of sleep showed a dose-dependent shortening of sleep latency, confirming the hypnotic action of the drug. Volunteers were aware of a decline in psychomotor performance, of some sleepiness on awakening, and decreased alertness after previous night doses of 7.5 and 10 mg. It is concluded that a dose of 7.5 mg is optimal, producing significant hypnotic effect with minimal residual impairment.

Antiviral activity of 5'-PAA and 5'-PFA phosphate esters of 2'-deoxyuridines.

The 5'-PAA and 5'-PFA phosphate esters of 5-bromo-2'-deoxyuridine (BUdR) were synthesized and their antiherpes virus activity was evaluated in vitro. Both compounds showed activity of the same order as the parent nucleoside, BUdR, against HSV-2 but were 4 to 12 times less potent against HSV-1. The 5'-PAA phosphate ester of BUdR (Ro 21-9875) was also active against varicella-zoster virus (VZV) and human cytomegalovirus (HCMV). The 5'-PAA phosphate ester of 5-bromovinyl-2'-deoxyuridine (BVdU) was also synthesized and showed good antiviral activity against HSV-1 only (ID50 = 1.3 mg/l). Further evaluation against selected mutants (TK- or PAAr) indicated a requirement for the expression of the virus-coded thymidine kinase (TK) for the antiviral activity of Ro 21-9875. Kinetic studies revealed non-competitive mixed inhibition of the viral enzyme by this compound. This suggests that it may have some intrinsic TK mediated activity though breakdown to its component parts is undoubtedly a significant contributing factor.

Examination of the relationship between the uptake system for 5-hydroxytryptamine and the high-affinity [3H]imipramine binding site--I. Inhibition by drugs.

The relationship between the binding site for imipramine and the uptake system for 5-hydroxytryptamine was examined. This was determined from the interaction between various drugs (including tricyclic antidepressants) and the high affinity accumulation of [3H]5-hydroxytryptamine in cortical synaptosomes from the rat, and with the high affinity binding of [3H]imipramine to cortical membranes of the rat. Imipramine and clomipramine, but not desipramine, were potent inhibitors of both binding of [3H]imipramine and the uptake of [3H]5-hydroxytryptamine. However, ouabain, panuramine and 5-hydroxytryptamine itself, all inhibited the binding of [3H]imipramine only at concentrations greater than those required to inhibit the uptake of [3H]5-hydroxytryptamine. Kinetic analysis revealed that inhibitors of the uptake system for 5-hydroxytryptamine produced inhibition by different mechanisms, but this did not account for their differential potency against uptake and binding. It is concluded that the binding site for [3H]imipramine and the uptake site for 5-HT are not directly linked and that drugs may inhibit the uptake of 5-HT at sites other than the binding site for [3H]imipramine.

A reassessment of the binding of [3H]rauwolscine to membranes from the rat cortex.

In order to fully resolve the binding profile of [3H]rauwolscine to membranes from the cortex of the rat, saturation, competition and association-dissociation data were analysed by means of computerised curve-fitting techniques. The binding isotherm for [3H]rauwolscine was best fitted to a two-component model consisting of a high-affinity, saturable site (approx. Kd 1.8 nM) and a low-affinity, apparently non-saturable, component. Displacement experiments revealed shallow inhibition curves for both antagonist and agonist ligands with a rank order of potency indicative of an interaction at the alpha 2-adrenoceptor. Inclusion of spiroperidol, but not prazosin, markedly steepened the antagonist, but not the agonist inhibition curves. In addition, spiroperidol attenuated, but did not eliminate, the low-affinity component in saturation experiments. Dissociation and association data revealed a biphasic paradigm, the more slowly-associating/dissociating component of which was sensitive to spiroperidol. It was concluded that [3H]rauwolscine binds to two sites on membranes of the rat cortex; a high-affinity site corresponding to alpha 2-adrenoceptors and a low-affinity, spiroperidol-sensitive component. The possible identity of the low-affinity site is discussed with particular emphasis on displacement data for [3H]rauwolscine and the interaction with rauwolscine in isolated organs.