Depression and sickness behavior are Janus-faced responses to shared inflammatory pathways

It is of considerable translational importance whether depression is a form or a consequence of sickness behavior. Sickness behavior is a behavioral complex induced by infections and immune trauma and mediated by pro-inflammatory cytokines. It is an adaptive response that enhances recovery by conserving energy to combat acute inflammation. There are considerable phenomenological similarities between sickness behavior and depression, for example, behavioral inhibition, anorexia and weight loss, and melancholic (anhedonia), physio-somatic (fatigue, hyperalgesia, malaise), anxiety and neurocognitive symptoms. In clinical depression, however, a transition occurs to sensitization of immuno-inflammatory pathways, progressive damage by oxidative and nitrosative stress to lipids, proteins, and DNA, and autoimmune responses directed against self-epitopes. The latter mechanisms are the substrate of a neuroprogressive process, whereby multiple depressive episodes cause neural tissue damage and consequent functional and cognitive sequelae. Thus, shared immuno-inflammatory pathways underpin the physiology of sickness behavior and the pathophysiology of clinical depression explaining their partially overlapping phenomenology. Inflammation may provoke a Janus-faced response with a good, acute side, generating protective inflammation through sickness behavior and a bad, chronic side, for example, clinical depression, a lifelong disorder with positive feedback loops between (neuro)inflammation and (neuro)degenerative processes following less well defined triggers

Changing character and waning impact of COVID-19 at a tertiary centre in Cape Town, South Africa.

BACKGROUND: The emergence of genetic variants of SARS-CoV-2 was associated with changing epidemiological characteristics throughout coronavirus disease 2019 (COVID-19) pandemic in population-based studies. Individual-level data on the clinical characteristics of infection with different SARS-CoV-2 variants in African countries is less well documented. OBJECTIVES: To describe the evolving clinical differences observed with the various SARS-CoV-2 variants of concern and compare the Omicron-driven wave in infections to the previous Delta-driven wave. METHOD: We performed a retrospective observational cohort study among patients admitted to a South African referral hospital with COVID-19 pneumonia. Patients were stratified by epidemiological wave period, and in a subset, the variants associated with each wave were confirmed by genomic sequencing. Outcomes were analysed by Cox proportional hazard models. RESULTS: We included 1689 patients were included, representing infection waves driven predominantly by ancestral, Beta, Delta and Omicron BA1/BA2 & BA4/BA5 variants. Crude 28-day mortality was 25.8% (34/133) in the Omicron wave period versus 37.1% (138/374) in the Delta wave period (hazard ratio [HR] 0.68 [95% CI 0.47-1.00] p = 0.049); this effect persisted after adjustment for age, gender, HIV status and presence of cardiovascular disease (adjusted HR [aHR] 0.43 [95% CI 0.28-0.67] p < 0.001). Hospital-wide SARS-CoV-2 admissions and deaths were highest during the Delta wave period, with a decoupling of SARS-CoV-2 deaths and overall deaths thereafter. CONCLUSION: There was lower in-hospital mortality during Omicron-driven waves compared with the prior Delta wave, despite patients admitted during the Omicron wave being at higher risk. CONTRIBUTION: This study summarises clinical characteristics associated with SARS-CoV-2 variants during the COVID-19 pandemic at a South African tertiary hospital, demonstrating a waning impact of COVID-19 on healthcare services over time despite epidemic waves driven by new variants. Findings suggest the absence of increasing virulence from later variants and protection from population and individual-level immunity

Prestressed cold-formed steel beams – parametric studies and design recommendations

Owing to their enhanced load-carrying and serviceability performances, prestressed coldformed steel beams can potentially open up new applications within the construction industry. In the proposed concept, an eccentric prestressing force is applied to cold-formed steel beams by means of a cable that is housed within a bottom hollow flange. During prestressing, tensile stresses are induced within the top region of the beam, thus delaying the occurrence of local instabilities under subsequent vertical loading. Consequently, the moment capacity of the beam is enhanced. Furthermore, owing to the prestressing, a pre-camber is also induced along the member, thus decreasing the overall vertical deflections significantly. Following discussion of the mechanical behaviour of the proposed beams, design recommendations are developed by employing interaction equations alongside the Direct Strength Method. Subsequently, finite element (FE) analysis is employed to investigate the effects of the prestress level and the section slenderness of the steel beam on the benefits obtained from the prestressing process. The parametric FE results are then utilised to assess the design recommendations

Design of prestressed cold-formed steel beams

Structural design rules for prestressed cold-formed steel beams, considering both the prestressing and imposed vertical loading stages, are presented herein. In the proposed approach, the cold-formed steel member is designed as a beam-column using linear interaction equations in conjunction with the Direct Strength Method (DSM), while the prestressed cable is designed by ensuring that its tensile capacity is not violated during the two loading stages. In the present paper, the design approach and the failure criteria, which define the permissible design zone for the prestressed system, are first introduced. The suitability of the design recommendations is then assessed by comparing a set of parametric finite element (FE) results for several combinations of prestress levels, beam geometries and cable sizes, with the corresponding design predictions. Finally, following reliability analysis, the implementation of the design recommendations is illustrated through a practical worked example