The COVID-19 pandemic: the public health reality.

The coronavirus disease (COVID-19), while mild in most cases, has nevertheless caused significant mortality. The measures adopted in most countries to contain it have led to colossal social and economic disruptions, which will impact the medium- and long-term health outcomes for many communities. In this paper, we deliberate on the reality and facts surrounding the disease. For comparison, we present data from past pandemics, some of which claimed more lives than COVID-19. Mortality data on road traffic crashes and other non-communicable diseases, which cause more deaths each year than COVID-19 has so far, is also provided. The indirect, serious health and social effects are briefly discussed. We also deliberate on how misinformation, confusion stemming from contrasting expert statements, and lack of international coordination may have influenced the public perception of the illness and increased fear and uncertainty. With pandemics and similar problems likely to re-occur, we call for evidence-based decisions, the restoration of responsible journalism and communication built on a solid scientific foundation.

Herbal and nutritional supplement use among college students in Qatar.

There is increasing demand for herbal and nutritional supplements in the Middle East. This study aimed to examine the use of supplements by college students in Qatar and to elucidate users' views about them. A total of 419 college students completed a self-administered questionnaire. Almost half of the respondents (49.6%) had used supplements (ever users), with 32.7% reporting using them in the previous 6 months (current users). Of the latter, 27.7% had used herbal supplements, 56.2% vitamins and minerals and 56.9% non-vitamin, non-mineral, non-herbal supplements. Many participants considered supplements to be safer and more effective than conventional medicines. Supplements were preferred over conventional medicines for the treatment of digestive conditions and common respiratory ailments and for weight management. Educating health-care providers about the benefits and risks of supplements is imperative and will enable health-care practitioners to guide patients in making informed decisions about supplement use.

Use of complementary and alternative medicine among midlife Arab women living in Qatar.

The prevalence of use of complementary and alternative medicine (CAM) is widespread and is growing worldwide. This cross-sectional study in Qatar examined the use of CAM and its correlates among Arab women in their midlife years. Women aged 40-60 years (n = 814) were recruited at primary care centres in Qatar and completed a specially designed, pre-tested questionnaire. Overall, 38.2% of midlife women in Qatar had used CAM in the previous 12 months. Nutritional remedies and herbal remedies were the most commonly used CAM therapies, followed by physical methods. Qatari nationality and higher level of education were independently associated with CAM use. Menopause transition status was not independently associated with use of CAM. The prevalence of CAM use by women in Qatar was high, consistent with other reports worldwide. It is essential to educate and inform patients and health-care providers about the benefits and limitations associated with CAM.

The effect of insulin intensification in children and young persons with Type 1 diabetes differs in relation to ethnic group; a prospective observational study.

AIMS: We prospectively evaluated the effect of insulin intensification on glycaemic control and lipid levels in children and young persons with Type 1 diabetes in relation to ethnicity. METHODS: In the first 2 years of a 3-year observation period, as part of routine clinical care, 231 children and young persons (40% white, 28% South Asian, 32% black) from a single clinic were offered intensive insulin therapy. After 2 years, 222 were on intensive therapy and their data were compared between ethnic groups at the end of year 3. RESULTS: We observed ethnic differences in HbA(1c) levels during the study [study beginning and end: white children and young persons 77 and 70 mmol/mol (9.2 and 8.6%) vs. South Asian 72 and 68 mmol/mol (8.7 and 8.4%) vs. black 83 and 79 mmol/mol (9.7 and 9.4%), P-value for ANCOVA = 0.007]. By study end, South Asians had the lowest HDL cholesterol (2.0 vs. 1.4 vs. 1.6 mmol/l, P-value = 0.03) and highest triglyceride levels (0.9 vs. 1.8 vs. 1.0 mmol/l, P-value = 0.001). In linear mixed modelling, after adjustment for socio-economic deprivation and other covariates: (1) black ethnicity was associated with poorer glycaemic control (P < 0.001) and (2) South Asian ethnicity was associated with higher triglyceride levels (P < 0.001), independent of HbA(1c). CONCLUSIONS: The effect of insulin intensification on glycaemic control and lipid profile in children and young persons with Type 1 diabetes differs in relation to ethnic group.

Photon spectra in NPL standard monoenergetic neutron fields.

A High Purity Germanium (HPGe) detector has been used to measure the photon spectra in the majority of monoenergetic neutron fields produced at NPL (0.144, 0.250, 0.565, 2.0, 5.0 and 16.5 MeV). The HPGe was characterised and then modelled to produce a response matrix. The measured pulse height spectra were then unfolded to produce photon fluence spectra. The new spectra were used to improve the photon to neutron dose equivalent ratios from some earlier work at NPL with Geiger-Muller tubes and electronic personal dosemeters.

Anaesthesia and epilepsy.

Epilepsy is the most common serious neurological disorder, with a prevalence of 0.5-1% of the population. While the traditional antiepileptic drugs (AEDs) still play a significant role in treatment of seizures, there has been an influx of newer agents over the last 20 yr, which are now in common usage. Anaesthetists are frequently faced with patients with epilepsy undergoing emergency or elective surgery and patients suffering seizures and status epilepticus in the intensive care unit (ICU). This review examines perioperative epilepsy management, the mode of action of AEDs and their interaction with anaesthetic agents, potential adverse effects of anaesthetic agents, and the acute management of seizures and refractory status epilepticus on the ICU. Relevant literature was identified by a Pubmed search of epilepsy and status epilepticus in conjunction with individual anaesthetic agents.

Moving forward with elective vascular work: a reflection on the impact of COVID-19 on a regional vascular hub.

INTRODUCTION: Following the initial COVID-19 surge in the UK, there was a national incentive for elective vascular surgery to be restricted to 'clean' sites to reduce perioperative cross-infection and subsequent mortality. We assessed the risk of dying from perioperatively acquired COVID-19 during the peak of the London outbreak. METHODS: Forty-three consecutive patients who had vascular (n=48) procedures in March and April 2020 at a regional hub serving five London hospitals were analysed. The patients were screened for COVID-19 in the 30-day postoperative period and the main outcome measure was mortality from COVID-19. A comparison was then made with patients who underwent minimally invasive procedures in our integrated interventional radiology department. Median follow-up was 41 days (interquartile range 8-58) overall. RESULTS: Three patients (7%) in the vascular group (median age 61 years, all diabetic, two male) died from COVID-19, all of whom tested positive postoperatively. Two others became positive but recovered. In comparison, two patients (2%) in the interventional radiology group died from COVID-19; however, one was positive prior to their procedure. CONCLUSION: Only urgent vascular cases should be performed during a COVID-19 surge. However, with growing waiting lists for elective surgery following the pandemic's second wave, further restrictions may not be a viable long-term solution. When prevalence of the disease is lower and if resources allow, resumption of care at 'hot' sites should be considered, if safety measures can be implemented. The advantages of minimally invasive surgery may also reduce risk.

Breastmilk with a high omega-6 to omega-3 fatty acid ratio induced cellular events similar to insulin resistance and obesity in 3T3-L1 adipocytes.

BACKGROUND: An imbalance of omega (n)-3 and n-6 polyunsaturated fatty acids (PUFA) during critical periods of development may have adverse effects on the health of the newborn in later life. OBJECTIVES: We hypothesized that breastmilk with higher n-6 to n-3 PUFA ratio will have higher inflammatory cytokines and initiate cellular events similar to insulin resistance and obesity. METHODS: Breastmilk was collected from healthy women who gave natural birth at full term. Breastmilk fatty acids were measured using gas chromatography; samples were pooled based on the n-6 to n-3 PUFA ratio (high, medium and low), and soluble cytokines were measured. Pooled samples were used to treat 3T3-L1 cells; mRNA expression of diacylglycerol acyltransferase2, stearoyl-CoA desaturase-1, leptin and RPLPO was measured. RESULTS: Breastmilk with a higher ratio of n-6 to n-3 PUFA showed higher pro-inflammatory cytokines; there was a direct correlation between n-6 PUFA and pro-inflammatory cytokines. Breastmilk with a higher ratio of n-6 to n-3 PUFA increased the expression of genes involved in lipogenesis. CONCLUSIONS: Pro-inflammatory cytokines in breastmilk are associated with higher levels of n-6 PUFA in breastmilk and has the capacity to alter adipose tissue metabolism to likely predispose the newborn to a higher risk of obesity in later life.

A diet enriched in longer chain omega-3 fatty acids reduced placental inflammatory cytokines and improved fetal sustainability of C57BL/6 mice.

Omega (n)-3 polyunsaturated fatty acids (PUFA) are important regulators of inflammatory response that may impact pregnancy outcome. The effects of breeding chow diets containing n-3 PUFA from either fish oil (FO) or soybean oil (SO) were investigated on tissue fatty acid composition, inflammatory cytokines and pregnancy outcome. Female C57BL/6 mice (7 weeks old) were fed FO or SO diets for 2 weeks before mating and throughout pregnancy. Animals were sacrificed before and during pregnancy at day 6.5, 12.5 and 18.5. The FO diet increased the incorporation of n-3 PUFA in placenta, with a concomitant decrease in the concentration of pro-inflammatory cytokines. The FO diet increased the mRNA expression of placental specific PUFA transporter, which coincided with accretion of n-3 PUFA in fetal brain. Sites of fetal resorption were noticeable in the SO group but not in the FO group. N-3 PUFA may improve fetal sustainability via altering cytokine levels.

Cytokines which signal through the LIF receptor and their actions in the nervous system.

A number of different cytokines, each initially characterized on the basis of very different biological activities, all have very similar signalling pathways and share a similar tertiary structure. These cytokines include leukaemia inhibitory factor, ciliary neuronotrophic factor, oncostatin M, growth-promoting activity and cardiotrophin 1. They all have been found to regulate a number of properties of cells of the developing and mature nervous system in vitro and thus are neuroregulatory cytokines. The actions of these cytokines include regulation of neurotransmitter phenotype, differentiation of neuronal precursor cells both in the peripheral nervous system and in the spinal cord, survival of differentiated neurons, and regulation of development of both astrocytes and oligodendrocytes. In addition, studies in animal models show that these factors can rescue sensory and motor neurons from axotomy-induced cell death, which suggests that they can act as trauma factors for injured neurons. Analysis of the expression patterns of the different neuroregulatory cytokines and their receptors reveals that the receptors are expressed throughout nervous system development and following trauma, whereas the cytokines show temporal and spatial specific expression patterns. This is consistent with the idea that specific cytokines have specific roles in neural development and repair, but that their signalling pathways are shared. The phenotypes of the receptor knockouts show clear deficits in nervous system development, indicating a crucial role for LIF receptor signalling. Knockouts of individual cytokines are less dramatic, but LIF and CNTF knockouts do reveal deficits in maintenance of motor neurons or following trauma. Thus, whereas LIF and CNTF have clear roles in maintenance and following trauma, it is unclear which of the cytokines is involved in nervous system development. In clinical terms, these findings add further support to the use of these cytokines in nervous system trauma and disease.

Diet fat alters expression of genes for enzymes of lipogenesis in lean and obese mice.

The objective of this experiment was to determine the effect of polyunsaturated fatty acids on gene expression for fatty acid synthase, acetyl CoA-carboxylase, malic enzyme, pyruvate kinase, and phosphoenolpyruvate carboxykinase in obese mice. Eight-week-old female lean and obese mice were fed semi-purified diets containing 20% (w/w) fat of either high or low polyunsaturated to saturated (P/S) fatty acid ratio for four weeks. Total RNA was isolated from liver and was hybridized to cDNA probes for the above enzymes. Consumption of a high P/S diet decreased mRNA levels for all the lipogenic enzymes studied in both lean and obese mice. Compared to lean mice, obese mice exhibited a higher mRNA level for fatty acid synthase, acetyl CoA-carboxylase, malic enzyme, and pyruvate kinase in animals fed either a high or low P/S diet. Enzyme-specific activities followed the same profile as the mRNA levels in both lean and obese mice fed a high or low P/S diet. The decrease in liver fatty acid synthase mRNA level was more pronounced in lean mice compared to obese mice, suggesting that the obese mice may be more resistant to polyunsaturated fatty acid feedback control of gene expression.

Insulin binding to liver nuclei from lean and obese mice is altered by dietary fat.

Insulin binding to the plasma membrane is known to be altered by modifying the membrane composition through dietary treatment. As insulin binding receptors are also present on nuclear membrane, this study was undertaken to investigate if specific binding of insulin to the liver nuclei is altered by diet. 8-wk-old female C57 B 6J lean and ob/ob mice were fed semipurified diets containing 20% (w/w) fat of either high or low polyunsaturated-to-saturated (P/S) fatty acid ratio for 4 wk. Liver nuclei were prepared, insulin binding was measured and nuclear phospholipids were isolated for lipid analysis. Insulin binding was highest in nuclei prepared from lean mice fed a high P/S diet. Specific binding of insulin to nuclei prepared from obese mice was also increased by the high P/S diet, but to a lesser extent compared to lean mice. Feeding a high P/S diet increased polyunsaturated fatty acid content of membrane phospholipids from both lean and ob/ob mice. Obese mice were characterized by higher levels of arachidonic acid and lower levels of linoleic acid in phosphatidylcholine. The present study establishes that insulin binding to liver nuclei is increased by feeding a high P/S diet, and that insulin binding to liver nuclei from obese mice is lower than from lean mice.

Bullying of junior doctors prevails in Irish health system: a bitter reality.

Workplace bullying in health systems is a well known fact. It leads to not only breakdown in teamwork but also has significant affect on the individual's personal life. True prevalence of bullying in junior doctors working in Ireland is unknown. Our aim of study was to find out the prevalence of bullying in junior doctors working hospitals in south and western counties of Ireland and to assess its effects on the productivity of work and family life and to identify the common source of bullying. We carried out a questionnaire survey. A total of 950 questionnaires were sent. Response rate was 51%. Our sample is 15% of the target population of all the hospital junior doctors. 30% of the responders claimed to be subjected to one or more bullying behaviors. Doctors from European Union (EU) reported significantly less rate of bullying compares to non EU doctors. Our results are in line with the results of studies conducted in United Kingdom. This study shows the magnitude and source of the problem. We conclude that bullying is a common problem in Irish health system. Increased awareness and zero tolerance are required to eradicate bullying.

Accuracy of admitting diagnosis in acute surgical patients by non consultant hospital doctors.

The incidence of accurate diagnosis made by non-consultant hospital doctors (NCHDs) is unknown in acute surgical admissions. There is a common assumption that reliance is made on excessive and inappropriate investigations. The aim of study was to assess the accuracy of admitting diagnosis by the NCHDs and the appropriateness of radiological investigations ordered. Data were collected on 100 consecutive acute surgical admissions. A final diagnosis was made in all the patients. 79 patients had accurate initial diagnosis (NCHDs). 23 scans were performed which confirmed the initial diagnosis. Out of 21 initial inaccurate diagnoses, final diagnosis was made on repeated clinical examination in 10, on imaging alone in 5 and by endoscopy or surgery in the remaining 6 patients. 11 patients had scans and 7 were appropriate. We conclude that 79% of diagnoses made by NCHDs are the accurate final diagnoses. The utilization of diagnostic modalities especially radiological imaging is highly appropriate. Our study suggests that the physical presence of a consultant on site may not lead to significant improvement to the delivery of health care to the Irish population.

Fatty acyl composition of lysophosphatidylcholine is important in atherosclerosis.

Atherosclerosis is a major cause of death for mankind. Although the pathophysiology of atherosclerosis is a complex and multifactorial process, growing body of evidence has identified phospholipids-mediated signaling as an important factor in the induction and progression of atherosclerosis. Lysophosphatidylcholine (LPC) is a major phospholipid in oxidized low-density lipoprotein, and is generally considered to be atherogenic. However, some studies have shown anti-atherogenic properties of LPC. The controversial findings surrounding the pro- or anti-atherogenic properties of LPC appear to be due to the chain length and the degree of saturation of the fatty acyl moiety of LPC. Studies have suggested that the presence of omega (n)-polyunsaturated fatty acids (PUFA) at the sn-1 position of LPC modulates the inflammatory response thereby making LPC anti-atherogenic. We have recently shown that feeding a diet high in n-3 PUFA resulted in the enrichment of LPC in both plasma and liver of C57BL/6 mice with n-3 PUFA. Others have also shown that supplementation with fish oil leads to preferential incorporation of n-3 PUFA into LPC. We also found that plasma obtained from mice fed a diet high in n-3 PUFA showed higher cholesterol efflux capacity compared to animals fed a low n-3 PUFA diet, despite no changes in high-density lipoprotein concentrations. We are therefore hypothesizing that n-3 PUFA enriched LPC has anti-atherogenic properties by promoting cholesterol efflux from macrophages and by reducing inflammation. Our anticipated long term objective is to establish that the fatty acyl moiety of LPC can be used as a potential biomarker for the risk of developing atherosclerosis. Validating this hypothesis would have a substantial impact on the public health with respect to early diagnosis of cardiovascular risks, and designing dietary based therapeutic strategies for the prevention and management of atherosclerosis and other heart related diseases.

Sensorimotor cortical projections to the primate cuneate nucleus.

The organization of the corticocuneate pathway was investigated in monkeys by using the anterograde and retrograde axonal transport of either horseradish peroxidase (HRP) or wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP). Injection of either tracer into the precentral cortex (centered on area 4) results in heavy anterograde labeling in the tegmental region, which lies immediately ventrolateral to the cuneate nucleus, particularly at levels caudal to the obex. On the other hand, injections of the same tracers involving areas 3b, 1, and 2 cause anterograde labeling mainly within the core (pars rotunda of Ferraro and Barrera, '35, Arch. Neurol. Psychol. 33:262-75) of the cuneate nucleus. Anterograde labeling is also evident in the rostral parts of the cuneate nucleus, especially after injections involving areas 1 and 2. Injections restricted largely to area 3b cause anterograde labeling preferentially in the core of the cuneate nucleus. After injection of HRP or WGA-HRP into the dorsal medulla, retrogradely labeled neurons are present both in the pre- and postcentral gyrus, but their location depends upon the sites and extent of the injection site. When the tracer diffuses into the underlying tegmental area, many retrogradely labeled neurons appear in the precentral motor cortex, principally in area 4 although some of them also occur in area 6. With smaller injections, largely restricted within the cuneate nucleus, most labeled neurons are present in the postcentral gyrus, with the largest population in areas 1 and 2; a smaller number of small neurons in area 3b are best demonstrated with WGA-HRP; and area 3a contains the smallest complement of retrogradely labeled neurons. The data from these studies suggest a segregation of pre- and postcentral afferents in the ventral tegmental region and the cuneate nucleus, respectively. These findings pertaining to the corticocuneate projection in the monkey are discussed in relation to the parallelism between monkeys and cats possible physiological implications of the anatomical organization described, and conflicting evidence in the neurophysiological observations obtained, by earlier investigators, by antidromic and orthodromic activation of this pathway.

Light and electron microscopic evidence for a direct corticospinal projection to superficial laminae of the dorsal horn in cats and monkeys.

The anterograde transport of horseradish peroxidase (HRP) and wheat germ agglutin conjugated to horseradish peroxidase (WGA-HRP) was employed in cats and monkeys to investigate, at both the light and electron microscopical levels, the contribution of the corticospinal tract (CST) to the superficial laminae of the dorsal horn. At the light microscopic level, this approach not only confirmed the previously documented pattern of CST termination, but also revealed a sparse projection to laminae VIII and IX of the cat and a prominent projection to the most superficial parts of the brachial dorsal horn, i.e., laminae I and II. Discrete injections involving particular cytoarchitectonic areas (4, 3a, 3b, and 1-2) of monkeys showed that the superficial laminae receive their corticofugal inputs primarily from areas 3b, 1, and 2. Electron microscopic observations were made on CST fibers and boutons which were labelled, after histochemical processing, with the reaction product of anterogradely transported WGA-HRP. The labelled fibers in the superficial laminae were small (+/- 0.5 micron), and boutons established mainly axodendritic contacts, contained mostly clear, spherical, or pleomorphic vesicles, but sometimes also displayed dense core vesicles. These boutons were primarily in lamina I and outer lamina II, but not in inner lamina II. The possible role of a direct monosynaptic pathway from the cerebral cortex to the superficial laminae of the dorsal horn is discussed in relation to the previous reports that laminae I and II play a significant role in nociception.

Thalamic projections to sensorimotor cortex in the macaque monkey: use of multiple retrograde fluorescent tracers.

We used several fluorescent dyes (Fast Blue, Diamidino Yellow, Rhodamine Latex Microspheres, Evans Blue, and Fluoro-Gold) in each of eight macaques, to examine the patterns of thalamic input to the sensorimotor cortex of macaques 12 months or older. Inputs to different zones of motor, premotor, and postarcuate cortex, supplementary motor area, and areas 3b/1 and 2/5 in the postcentral cortex, were examined. Coincident labeling of thalamocortical neuron populations with different dyes (1) increased the precision with which their soma distributions could be related within thalamic space, and (2) enabled the detection by double labeling, of individual thalamic neurons that were common to the thalamic soma distributions projecting to separate, dye-injected cortical zones. Double-labeled thalamic neurons projecting to sensorimotor cortex were rarely seen in mature macaques, even when the injection sites were only 1-1.5 mm apart, implying that their terminal arborizations were quite restricted horizontally. By contrast, separate neuron populations in each thalamic nucleus with input to sensorimotor cortex projected to more than one cytoarchitecturally distinct cortical area. In ventral posterior lateral (oral) (VPLo), for example, separate populations of cells sent axons to precentral medial, and lateral area 4, medial premotor, and postarcuate cortex, as well as to supplementary motor area. Extensive convergence of thalamic input even to the smallest zones of dye uptake in the cortex (approximately 0.5 mm3) characterized the sensorimotor cortex. The complex forms of these projection territories were explored using 3-dimensional reconstructions from coronal maps. These projection territories, while highly ordered, were not contained by the cytoarchitectonic boundaries of individual thalamic nuclei. Their organization suggests that the integration of the diverse information from spinal cord, cerebellum, and basal ganglia that is needed in the execution of complex sensorimotor tasks begins in the thalamus.

Thalamic projections to sensorimotor cortex in the newborn macaque.

In the present experiments thalamocortical projections to different functional areas of the newborn (or prematurely delivered) macaque's sensorimotor cortex were labeled using retrogradely transported fluorescent dyes. Several dyes were used in each animal to (1) enable the direct comparison of the soma distributions of different thalamocortical projections within thalamic space, and (2) identify by double labeling neurons shared between these distributions. The projection patterns in the newborn macaque were compared with those of the mature animal reported by Darian-Smith et al. (J. Comp. Neurol. 1990;298:000-000). The main observations were (1) all thalamocortical projections to the sensorimotor cortex of the mature macaque are well established by embryonic days 146-150, as was shown by labeling these pathways in infants delivered by cesarean section, (2) a significant number of thalamocortical neurons in the newborn were double-labeled following dye injections into different pre- or postcentral areas, and where the margins of the dye uptake zones were separated by 3-8 mm, and (3) extensive projections from the anterior pulvinar nucleus to the motor and premotor cortex, and to the supplementary motor cortex were labeled in the newborn macaque. Both the exuberant terminal arborizations, and the precentral pulvinar projections were diminished by the 6th postnatal month, and absent in the mature macaque. The role of epigenetic determinants of these postnatal events is briefly considered.