Highly Thermotolerant SARS-CoV-2 Vaccine Elicits Neutralising Antibodies against Delta and Omicron in Mice

As existing vaccines fail to completely prevent COVID-19 infections or community transmission, there is an unmet need for vaccines that can better combat SARS-CoV-2 variants of concern (VOC). We previously developed highly thermo-tolerant monomeric and trimeric receptor-binding domain derivatives that can withstand 100 °C for 90 min and 37 °C for four weeks and help eliminate cold-chain requirements. We show that mice immunised with these vaccine formulations elicit high titres of antibodies that neutralise SARS-CoV-2 variants VIC31 (with Spike: D614G mutation), Delta and Omicron (BA.1.1) VOC. Compared to VIC31, there was an average 14.4-fold reduction in neutralisation against BA.1.1 for the three monomeric antigen-adjuvant combinations and a 16.5-fold reduction for the three trimeric antigen-adjuvant combinations; the corresponding values against Delta were 2.5 and 3.0. Our findings suggest that monomeric formulations are suitable for upcoming Phase I human clinical trials and that there is potential for increasing the efficacy with vaccine matching to improve the responses against emerging variants. These findings are consistent with in silico modelling and AlphaFold predictions, which show that, while oligomeric presentation can be generally beneficial, it can make important epitopes inaccessible and also carries the risk of eliciting unwanted antibodies against the oligomerisation domain.     

An International Comparison of Web-based Reporting About Health Care Quality: Content Analysis

Background

On more and more websites, consumers are provided with public reports about health care. This move toward provision of more comparative information has resulted in different information types being published that often contain contradictory information.

Objective

The objective was to assess the current state of the art in the presentation of online comparative health care information and to compare how the integration of different information types is dealt with on websites. The content analysis was performed in order to provide website managers and Internet researchers with a resource of knowledge about presentation formats being applied internationally.

Methods

A Web search was used to identify websites that contained comparative health care information. The websites were systematically examined to assess how three different types of information (provider characteristics and services, performance indicators, and health care user experience) were presented to consumers. Furthermore, a short survey was disseminated to the reviewed websites to assess how the presentation formats were selected.

Results

We reviewed 42 websites from the following countries: Australia, Canada, Denmark, Germany, Ireland, the Netherlands, Norway, the United Kingdom, the United States, and Sweden. We found the most common ways to integrate different information types were the two extreme options: no integration at all (on 36% of the websites) and high levels of integration in single tables on 41% of the websites). Nearly 70% of the websites offered drill down paths to more detailed information. Diverse presentation approaches were used to display comparative health care information on the Internet. Numbers were used on the majority of websites (88%) to display comparative information.

Conclusions

Currently, approaches to the presentation of comparative health care information do not seem to be systematically selected. It seems important, however, that website managers become aware of the complexities inherent in comparative information when they release information on the Web. Important complexities to pay attention to are the use of numbers, the display of contradictory information, and the extent of variation among attributes and attribute levels. As for the integration of different information types, it remains unclear which presentation approaches are preferable. Our study provides a good starting point for Internet research to further address the question of how different types of information can be more effectively presented to consumers.     

Ischemic vascular disease and solid cancers: opposing ends of the angiogenic spectrum?

Angiogenesis is a key pathway crucial to the patho-physiology of both vascular disease and solid cancer. In physiological conditions, a fine balance of pro- and anti-angiogenic factors is maintained as part of normal homeostatic mechanisms. It is widely accepted that excess angiogenesis influences the development or progression of tumours whilst insufficient angiogenesis may predispose to ischemic vascular disease. Although there are some factors, which predispose to both cancers and vascular disease, we believe there is a reasonable body of literature that suggests an inverse association between the two. We hypothesise that pro-angiogenic and anti-angiogenic phenotypes exist in the population. This may be due to a combination of underlying genetic variations and/or environmental factors. Pro-angiogenic phenotypes would have increased susceptibility to solid cancers and decreased predisposition to cardiovascular diseases and vice versa with the anti-angiogenic phenotypes. We propose that genetic and environmental factors causing a shift in the balance of angiogenesis will predispose individuals towards one group of pathologies while protecting them from another. Evaluation of this hypothesis will in the first instance involve carefully designed large population based observational studies to determine if an inverse relationship exists between the predisposition to ischemic vascular disease and the predisposition to solid cancer. Further detailed study of the pathways and underlying mechanisms of angiogenesis especially in disease states would facilitate better understanding of its regulation. Evaluation and validation of molecular markers that affect the 'angiogenesis pathway' may be helpful in determining the angiogenic potential of individual subjects. Determining where individuals lie along this spectrum may have a potential role in the prediction and stratification of risk of cancer and vascular disease. Modifying risk for patients at high risk of disease at the two opposing ends of the spectrum may then be possible by either lifestyle or dietary alterations or drugs targeting the angiogenic pathway.     

医药类专业本科物理课程的设置及目标与定位探讨

目的：探讨物理课程在高等医药类专业教育中的作用与地位。方法：对全国部分城市不同类别医院从业医务工作者进行调查，综合国际医学教育标准和我国现实医学教育以及医疗服务行业状况进行分析。结果：探讨了我国高等医药类专业教育中物理课程的设置及目标与定位问题，给出了明确的课程定位与设置标准。结论：现代医学高等教育不应忽视或淡化物理课程在医学人才培养中素质教育和专业水平提高的积极作用与基础地位，在有限的学时空间内合理安排基础性内容和与专业素质培养相关的应用内容。     

Epstein Barr virus latent membrane protein-1 in Hodgkin's lymphoma in Nigerians

Background

The burden of lymphomas on the health care system in Nigeria is enormous. Correct diagnosis and identification of aetiological factor are important steps in reducing this burden.

Methods

Eight cases diagnosed as HL within a period of six years at the Obafemi Awolowo University teaching Hospital, Ile-Ife, Nigeria by haematoxylin and eosin (Hand E) only were immunophenotyped using the indirect immunoperoxidase method. Epstein-Barr virus latent membrane protein-1 (LMP-1), CD15 and CD30 immunohistochemistry was also performed. The clinical characteristics of each patient were documented.

Objectives

To document the frequency of involvement of Epstein-Barr virus in cases of HL seen in a university hospital in Nigeria.

Results

Out of the eight cases diagnosed by H&E as HL immunophenotyping showed only five were HL. The rest were non-Hodgkin''s lymphoma (2 diffuse large B-cell and 1 null cell ALCL). All were cases of classical HL with 60% being of the mixed cellularity (MC) subtype. There were 2 males and 3 females with ages ranging from 7 years to 40 years. All presented with cervical lymphadenopathy and three had splenomegaly in addition. 60% of the tumour was EBV positive, all of the MC subtype. Three patients had chemotherapy. Eventually all were lost to follow-up. There was no case of the nodular lymphocyte predominance variant.

Conclusion

Mixed cellularity is the most common subtype and is the only subtype associated with EBV positivity in this study. Epstein-Barr virus probably plays an important role in the aetiology of HL in Nigerians.Running title: Epstein-Barr virus, Hodgkin''s lymphoma in Nigerians     

Role of massage therapy on reduction of neonatal hyperbilirubinemia in term and preterm neonates: a review of clinical trials

Background: Neonatal hyperbilirubinemia (NNH) is one of the leading causes of admissions in nursery throughout the world. It affects approximately 2.4–15% of neonates during the first 2 weeks of life.

Aims: To evaluate the role of massage therapy for reduction of NNH in both term and preterm neonates.

Method: The literature search was done for various randomized control trials (RCTs) by searching the Cochrane Library, PubMed, and EMBASE.

Results: This review included total of 10 RCTs (two in preterm neonates and eight in term neonates) that fulfilled inclusion criteria. In most of the trials, Field massage was given. Six out of eight trials reported reduction in bilirubin levels in term neonates. However, only one trial (out of two) reported significant reduction in bilirubin levels in preterm neonates. Both trials in preterm neonates and most of the trials in term neonates (five trials) reported increased stool frequencies.

Conclusion: Role of massage therapy in the management of NNH is supported by the current evidence. However, due to limitations of the trials, current evidences are not sufficient to use massage therapy for the management of NNH in routine practice.     

A Distributed Model of Carbohydrate Transport and Metabolism in the Liver during Rest and High-Intensity Exercise

A model of reaction and transport in the liver was developed that describes the metabolite concentration and reaction flux dynamics separately within the tissue and blood domains. The blood domain contains equations for convection, axial dispersion, and transport to the surrounding tissue; and the tissue domain consists of reactions representing key carbohydrate metabolic pathways. The model includes the metabolic heterogeneity of the liver by incorporating spatial variation of key enzymatic maximal activities. Simulation results of the overnight fasted, resting state agree closely with experimental values of overall glucose uptake and lactate output by the liver. The incorporation of zonation of glycolytic and gluconeogenic enzyme activities causes the expected increase in glycolysis and decrease in gluconeogenesis along the sinusoid length from periportal to perivenous regions, while fluxes are nearly constant along the sinusoid length in the absence of enzyme zonation. These results confirm that transport limitations are not sufficient to account for the observed tissue heterogeneity of metabolic fluxes. Model results indicate that changes in arterial substrate concentrations and hepatic blood flow rate, which occur in the high-intensity exercise state, are not sufficient to shift the liver metabolism enough to account for the 5-fold increase in hepatic glucose production measured during exercise. Changes in maximal activities, whether caused by exercise-induced changes in insulin, glucagon, or other hormones are shown to be needed to achieve the expected glucose output. This model provides a framework for evaluating the relative importance to hepatic function of various phenomenological changes that occur during exercise. The model can also be used to assess the potential effect of metabolic heterogeneity on metabolism.     

Isotonic versus hypotonic fluid supplementation in term neonates with severe hyperbilirubinemia - a double-blind, randomized, controlled trial

Aim: To compare the incidence of hyponatremia in full‐term neonates with severe hyperbilirubinemia, receiving intravenous fluid supplementation with 0.2% saline in 5% dextrose versus 0.9% saline in 5% dextrose, to prevent blood exchange transfusion (BET). Methods: In this double‐blind, randomized, controlled trial, full ‐ term newborns (≥37 weeks), appropriate for gestational age, with severe non‐haemolytic hyperbilirubinemia (serum bilirubin ≥ 20 mg/dL) were enrolled. Eligible neonates were randomized to receive either 0.2% saline in 5% dextrose (hypotonic fluid group) or 0.9% saline in 5% dextrose (isotonic fluid group) over 8 hrs, in addition to phototherapy. The primary outcome was proportion of neonates developing hyponatremia (serum Na < 135 mmol/L) after 8 h. Results: Forty‐two neonates were analysed in each group. Proportion of neonates developing hyponatremia after 8 h was higher in hypotonic fluid group as compared to isotonic fluid group (48.8% vs. 10.5%, p < 0.001). However, a larger proportion in isotonic fluid group developed hypernatremia (39.5% vs. 12.2%, p < 0.001). The rate of BET was similar in both groups. Conclusion: In full‐term neonates with severe hyperbilirubinemia, administration of hypotonic fluid to prevent BET was associated with a higher incidence of hyponatremia while isotonic fluid was associated with an increased incidence of hypernatremia.