HIV and an Ageing Population-What Are the Medical, Psychosocial, and Palliative Care Challenges in Healthcare Provisions.

The continuing increase in patient numbers and improvement in healthcare provisions of HIV services in the UK, alongside the effectiveness of combined antiretroviral therapy (cART), has resulted in increasing numbers of the ageing population among people living with HIV (PLWH). It is expected that geriatricians will need to deal with many older people living with HIV (OPLWH) as life expectancy increases. Therefore, geriatric syndromes in OPLWH will be similar to the normal population, such as falls, cognitive decline, frailty, dementia, hypertension, diabetes and polypharmacy. The increase in the long-term use of cART, diabetes, dyslipidaemia and hypertension may lead to high prevalence of cardiovascular disease (CVD). The treatment of such conditions may lead to polypharmacy and may increase the risk of cART drug-drug interactions. In addition, the risk of developing infection and cancer is high. OPLWH may develop an early onset of low bone mineral density (BMD), osteoporosis and fractures. In this review, we have also provided potential psychosocial aspects of an ageing population with HIV, addressing issues such as depression, stigma, isolation and the need for comprehensive medical and psychosocial care through an interdisciplinary team in a hospital or community setting. OPLWH have a relatively high burden of physical, psychological, and spiritual needs and social difficulties, which require palliative care. The holistic type of palliative care that will improve physical, emotional and psychological wellbeing is discussed in this review.

Effects of Ramadan Fasting on Glycaemic Control Among Patients with Type 2 Diabetes: Systematic Review and Meta-analysis of Observational Studies.

INTRODUCTION: The prevalence of type 2 diabetes (T2D) is increasing around the world. Although Muslims with a physical illness are exempted from fasting during the month of Ramadan, a great number still choose to fast, often without medical consultations. The aim of this systematic review and meta-analysis was to investigate the impact of observing Ramadan fasting (RF) on glycaemic control in patients with T2D. METHODS: The Web of Science, Scopus, EBSCOhost, CINAHL, ScienceDirect, Cochrane Library, ProQuest Central and Europe PubMed Central (Medline) databases were searched for relevant studies published between January 2000 and December 2021. Observational studies that examined the changes in body weight (BW) and glucose parameters (glycosylated haemoglobin [HbA1c] and fasting blood glucose [FBG]), before and after RF among different age groups with T2D were included in the systemic review and meta-analysis. Effect sizes for the tested outcomes were calculated as weighted mean difference (WMD), with their confidence intervals (CI). Quality assessment was examined using the National Heart, Lung, and Blood Institute (NHLBI) tool. RESULTS: Of the 1592 identified records, 12 studies conducted in Middle Eastern and Asian countries were eligible and included in the quantitative analyses. The quality of the retrieved studies was evaluated and found to range between fair (83%) and good (17%). These 12 studies included 5554 participants of whom 54% were males and 46% were females. Our pooled analysis demonstrated that HbA1c and FBG levels significantly decreased after RF when compared to the pre-fasting levels (WMD = 0.55 mg/dl, 95% CI 0.33-0.77, P < 0.00001, Ι2 = 93% and WMD = 12.42, CI 6.46-18.38, P < 0.0001, Ι2 = 81%, respectively). However, the difference in BW in fasting patients after RF versus the pre-fasting stage was non-significant. Although, young patients with T2D were enrolled in the 12 selected studies, we did not find any studies that solely focussed on this group. CONCLUSION: The impact of RF on adult patients with T2D is associated with favorable outcomes. However, future studies should evaluate data from young adults separately. In addition, it is essential to identify the effects of the number of fasting days (level of exposure), diet, level of physical activity and sleeping pattern on optimal glycaemic control. This information could be utilized by medical professionals as a non-pharmacological therapeutic method for management of diabetes in patients who are willing to practice fasting during Ramadan and other months of the year. STUDY REGISTRATION: PROSPERO: CRD42022314752.

Impact of COVID-19 on Children and Young Adults With Type 2 Diabetes: A Narrative Review With Emphasis on the Potential of Intermittent Fasting as a Preventive Strategy.

Background: The world is still struggling to control the COVID-19 pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The level of uncertainty regarding the virus is still significantly high. The virus behaves differently in children and young adults. Most children and adolescents are either asymptomatic or have mild symptoms. They generally have a very good prognosis. However, it is not well-known whether children and young adults with type 2 diabetes are at risk of getting a severe infection of COVID-19. Many Muslim children with type 2 diabetes have been performing dawn to dusk fasting during the month of Ramadan, before and during the COVID-19 pandemic, and the impact of this on their health has not been well investigated. Previous studies in adults have suggested that intermittent fasting may be beneficial in different ways including reversal of type 2 diabetes and prevention of COVID-19 infection. Objective: The primary aim of this narrative review is to summarise the impacts of the COVID-19 pandemic on children and young adults with type 2 diabetes, and to identify the knowledge gaps in the literature. It also explores the potential of intermittent fasting in reversing the pathogenesis of diabetes and highlighting how this approach could prevent these patients from developing chronic complications. Methods: This narrative review has been produced by examining several databases, including Google Scholar, Research Gate, PubMed, Cochrane Library, MEDLINE (EBSCO), and Web of Science. The most common search terms used were "COVID-19 AND Children", "SARS-CoV-2 AND/OR Children", "COVID-19 AND Diabetes" "COVID-19 Epidemiology", "COVID-19 AND Ramadan fasting", "COVID-19 and Intermittent fasting." All the resources used are either peer-reviewed articles/reports and/or official websites of various media, governmental and educational organisations. Results: Having reviewed the currently limited evidence, it has been found that the incidence of COVID-19 among children with type 2 diabetes seems to be not much different from children without diabetes. However, these patients are still vulnerable to any infection. Several studies have reported that prevention programmes such as intermittent fasting are effective to protect these groups of patients from developing any complications. Moreover, observing Ramadan fasting as a type of intermittent fasting could be beneficial for some children with established diabetes, prediabetes and people at risk. Conclusion: Children and young adults with type 2 diabetes are not at risk of severe COVID-19 infection as the case in adults with diabetes. More research is needed to identify the impact of COVID-19 and to investigate the efficacy and safety of intermittent fasting, including Ramadan fasting, among these age groups. Implementing these cost-effective programmes may have a great impact in minimising the incidence of diabetes. Moreover, this could be effective particularly at prediabetes stage by preventing these people from going onto develop type 2 diabetes and taking medications for the rest of their life and protecting people from complications linked to disease and infection.

Detection of a Yersinia pestis gene homologue in rodent samples.

A homologue to a widely used genetic marker, pla, for Yersinia pestis has been identified in tissue samples of two species of rat (Rattus rattus and Rattus norvegicus) and of mice (Mus musculus and Apodemus sylvaticus) using a microarray based platform to screen for zoonotic pathogens of interest. Samples were from urban locations in the UK (Liverpool) and Canada (Vancouver). The results indicate the presence of an unknown bacterium that shares a homologue for the pla gene of Yersinia pestis, so caution should be taken when using this gene as a diagnostic marker.

Development of a DNA-based microarray for the detection of zoonotic pathogens in rodent species.

The demand for diagnostic tools that allow simultaneous screening of samples for multiple pathogens is increasing because they overcome the limitations of other methods, which can only screen for a single or a few pathogens at a time. Microarrays offer the advantages of being capable to test a large number of samples simultaneously, screening for multiple pathogen types per sample and having comparable sensitivity to existing methods such as PCR. Array design is often considered the most important process in any microarray experiment and can be the deciding factor in the success of a study. There are currently no microarrays for simultaneous detection of rodent-borne pathogens. The aim of this report is to explicate the design, development and evaluation of a microarray platform for use as a screening tool that combines ease of use and rapid identification of a number of rodent-borne pathogens of zoonotic importance. Nucleic acid was amplified by multiplex biotinylation PCR prior to hybridisation onto microarrays. The array sensitivity was comparable to standard PCR, though less sensitive than real-time PCR. The array presented here is a prototype microarray identification system for zoonotic pathogens that can infect rodent species.

A recombinant avian infectious bronchitis virus expressing a heterologous spike gene belonging to the 4/91 serotype.

We have shown previously that replacement of the spike (S) gene of the apathogenic IBV strain Beau-R with that from the pathogenic strain of the same serotype, M41, resulted in an apathogenic virus, BeauR-M41(S), that conferred protection against challenge with M41. We have constructed a recombinant IBV, BeauR-4/91(S), with the genetic backbone of Beau-R but expressing the spike protein of the pathogenic IBV strain 4/91(UK), which belongs to a different serogroup as Beaudette or M41. Similar to our previous findings with BeauR-M41(S), clinical signs observations showed that the S gene of the pathogenic 4/91 virus did not confer pathogenicity to the rIBV BeauR-4/91(S). Furthermore, protection studies showed there was homologous protection; BeauR-4/91(S) conferred protection against challenge with wild type 4/91 virus as shown by the absence of clinical signs, IBV RNA assessed by qRT-PCR and the fact that no virus was isolated from tracheas removed from birds primarily infected with BeauR-4/91(S) and challenged with IBV 4/91(UK). A degree of heterologous protection against M41 challenge was observed, albeit at a lower level.Our results confirm and extend our previous findings and conclusions that swapping of the ectodomain of the S protein is a precise and effective way of generating genetically defined candidate IBV vaccines.

Structural consideration of the formation of the activation complex between the staphylokinase-like streptococcal plasminogen activator PadA and bovine plasminogen.

The characteristics of a streptococcal plasminogen activator (PA) displaying specificity for ruminant plasminogen (Plg) were defined using molecular approaches. The 16-kDa secreted protein PadA was found to be prevalent in Streptococcus dysgalactiae subspecies dysgalactiae isolated from cases of bovine mastitis and septic arthritis in lambs. PadA was able to activate bovine, ovine and caprine Plg, but not human Plg. Amino acid sequence analysis identified a limited level of homology to other streptococcal PAs, including streptokinase; however, PadA was found to align well with and match in size the staphylococcal PA, staphylokinase. Recombinant PadA was used to investigate interaction with bovine Plg, leading to formation of an activator complex that was capable of recruiting and converting further substrate Plg into plasmin. Individual non-overlapping peptides of PadA or bovine microplasminogen were found to block the interaction between PadA and bovine Plg, preventing the formation of the activation complex. Homology modelling based upon structures of staphylokinase complexed with human microplasminogen supported these findings by placing critical residues in close proximity to the plasmin component of the activation complex.

DetectiV: visualization, normalization and significance testing for pathogen-detection microarray data.

DNA microarrays offer the possibility of testing for the presence of thousands of micro-organisms in a single experiment. However, there is a lack of reliable bioinformatics tools for the analysis of such data. We have developed DetectiV, a package for the statistical software R. DetectiV offers powerful yet simple visualization, normalization and significance testing tools. We show that DetectiV performs better than previously published software on a large, publicly available dataset.

Functional analysis of lymphostatin homologues in enterohaemorrhagic Escherichia coli.

Enteropathogenic Escherichia coli contain a large chromosomal gene (lifA) that encodes lymphostatin, a predicted 365 kDa protein that inhibits the mitogen-activated proliferation of peripheral blood lymphocytes and lamina propria mononuclear cells and the synthesis of proinflammatory cytokines. Non-O157 serotypes of enterohaemorrhagic E. coli (EHEC) contain a highly homologous gene, designated efa1 (EHEC factor for adherence), which influences adherence to epithelial cells in vitro and intestinal colonization in calves. Serotype O157:H7 EHEC strains contain a truncated version of this gene (efa1') and a pO157-encoded homologue of lifA/efa1 (toxB). Here we report for the first time that efa1 inhibits mitogen-activated proliferation of bovine peripheral blood lymphocytes by EHEC O103:H2, but that E. coli K-12 strains expressing the N-terminal and central portions of the protein lack activity. While a Shiga toxin-negative E. coli O157:H7 strain was shown to possess lymphostatin-like activity, deletion of efa1' or toxB, singly or in combination, failed to significantly relieve the inhibitory effect.

Complex interactions between bovine plasminogen and streptococcal plasminogen activator PauA.

The interactions between bovine plasminogen and the streptococcal plasminogen activator PauA that culminate in the generation of plasmin are not fully understood. Formation of an equimolar activation complex comprising PauA and plasminogen by non-proteolytic means is a prerequisite to the recruitment of substrate plasminogen; however the determinants that facilitate these interactions have yet to be defined. A mutagenesis strategy comprising nested deletions and random point substitutions indicated roles for both amino and carboxyl-terminal regions of PauA and identified further essential residues within the alpha domain of the plasminogen activator. A critical region within the alpha domain was identified using non-overlapping PauA peptides to block the interaction between PauA and bovine plasminogen, preventing formation of the activation complex. Homology modelling of the activation complex based upon the known structures of streptokinase complexed with human plasmin supported these findings by placing critical residues in close proximity to the plasmin component of the activation complex.