The emergence of international food safety standards and guidelines: understanding the current landscape through a historical approach

Following the Second World War, the Food and Agriculture Organization (FAO) and the World Health Organization (WHO) teamed up to construct an International Codex Alimentarius (or 'food code') which emerged in 1963. The Codex Committee on Food Hygiene (CCFH) was charged with the task of developing microbial hygiene standards, although it found itself embroiled in debate with the WHO over the nature these standards should take. The WHO was increasingly relying upon the input of biometricians and especially the International Commission on Microbial Specifications for Foods (ICMSF) which had developed statistical sampling plans for determining the microbial counts in the final end products. The CCFH, however, was initially more focused on a qualitative approach which looked at the entire food production system and developed codes of practice as well as more descriptive end-product specifications which the WHO argued were 'not scientifically correct'. Drawing upon historical archival material (correspondence and reports) from the WHO and FAO, this article examines this debate over microbial hygiene standards and suggests that there are many lessons from history which could shed light upon current debates and efforts in international food safety management systems and approaches

Venous hemodynamics in neurological disorders: an analytical review with hydrodynamic analysis.

Venous abnormalities contribute to the pathophysiology of several neurological conditions. This paper reviews the literature regarding venous abnormalities in multiple sclerosis (MS), leukoaraiosis, and normal-pressure hydrocephalus (NPH). The review is supplemented with hydrodynamic analysis to assess the effects on cerebrospinal fluid (CSF) dynamics and cerebral blood flow (CBF) of venous hypertension in general, and chronic cerebrospinal venous insufficiency (CCSVI) in particular.CCSVI-like venous anomalies seem unlikely to account for reduced CBF in patients with MS, thus other mechanisms must be at work, which increase the hydraulic resistance of the cerebral vascular bed in MS. Similarly, hydrodynamic changes appear to be responsible for reduced CBF in leukoaraiosis. The hydrodynamic properties of the periventricular veins make these vessels particularly vulnerable to ischemia and plaque formation.Venous hypertension in the dural sinuses can alter intracranial compliance. Consequently, venous hypertension may change the CSF dynamics, affecting the intracranial windkessel mechanism. MS and NPH appear to share some similar characteristics, with both conditions exhibiting increased CSF pulsatility in the aqueduct of Sylvius.CCSVI appears to be a real phenomenon associated with MS, which causes venous hypertension in the dural sinuses. However, the role of CCSVI in the pathophysiology of MS remains unclear

Tight junctions and the modulation of barrier function in disease

Tight junctions create a paracellular barrier in epithelial and endothelial cells protecting them from the external environment. Two different classes of integral membrane proteins constitute the tight junction strands in epithelial cells and endothelial cells, occludin and members of the claudin protein family. In addition, cytoplasmic scaffolding molecules associated with these junctions regulate diverse physiological processes like proliferation, cell polarity and regulated diffusion. In many diseases, disruption of this regulated barrier occurs. This review will briefly describe the molecular composition of the tight junctions and then present evidence of the link between tight junction dysfunction and disease

Real-World Outcomes of Aggressive B-Cell Non-Hodgkin Lymphoma in People Living with HIV (PLWH) Treated in Australia: An Australasian Lymphoma Alliance Study

Abstract Background Modern antiretroviral therapy (ART) has reduced HIV associated morbidity and mortality, and allowed a similar treatment approach of aggressive lymphomas in PLWH to that of their HIV negative counterparts. Australia is an ethnically diverse country with a low HIV prevalence and an excellent population-wide ART coverage and adherence in PLWH. We aimed to describe the real-world Australian experience in managing PLWH diagnosed with diffuse large B cell lymphoma (DLBCL) and Burkitt lymphoma (BL), and compare our treatment approach and outcomes against international data. Methods This was a retrospective, multicenter study conducted by the Australasian Lymphoma Alliance across 6 centers in 5 states. HIV positive patients with biopsy proven BL and DLBCL, diagnosed between 1st January 2009 and 31st December 2019 were identified through each institution's database. Baseline patient and disease characteristics, treatment exposure and outcomes were extracted from hospital medical records. Descriptive statistics, and survival analyses were performed as appropriate. Results 44 patients (24 DLBCL, 20 BL) were included in the analysis. The median age was 52 years (range 32-78). The median follow-up was 1.8 years (range 0.1-13.1). 36 (82%) patients presented with advanced stage (III-IV) disease. 28 (64%) were defined as high-risk based on disease specific IPI scoring systems. The mean CD4 count was 334 cells/μL at diagnosis and 10 (23%) patients had a CD4 count of &amp;lt;100 cells/μL. 23 (52%) had a HIV viral load &amp;lt;50 copies/ml. 12 (27%) were diagnosed with HIV at the time of lymphoma diagnosis (Mean CD4 count 191 cells/μL, mean viral load 665,612 copies/ml). 41 (93%) patients received chemotherapy with curative intent and 39 (88%) received Rituximab. 37 (84%) were given concurrent ART and chemo(immuno)therapy. 11 (55%) of BL patients were treated with CODOX-M/IVAC or HyperCVAD followed by 6 (30%) with Da-EPOCH. 14 (58%) of DLBCL patients received CHOP-based therapy with 11 (45%) receiving more intensive regimens (Da-EPOCH, HyperCVAD or CODOX-M/IVAC). In the whole cohort, median number of chemotherapy cycles delivered was 6, 6, 4 and 3 for CHOP, Da-EPOCH, CODOX-M/IVAC and HyperCVAD respectively. CR rates after first-line curative intent therapy were 75% and 83% in BL and DLBCL respectively. All treatment response assessments were made by positron emission tomography. Grade 3-4 toxicity was significant higher in patients receiving intensive chemotherapy (77% vs 29%, p=0.015). Total treatment related mortality was 5% (2 died of bacterial sepsis). The 2-year OS was 77% (95% CI 61-88); 67% for BL (95% CI 46-88) and 81% for DLBCL (95% CI 53-90)]. 2-year PFS was 67% for BL (95% CI 40-83) and 77% for DLBCL (95% CI 53-89). An initial drop of mean CD4 count post treatment was observed (334 to 214 cells/μL), followed by a rise after 6 and 12 months (290 and 431 cells/μL respectively) (fig 1). At 6 months post chemotherapy, 83% of patients had a HIV viral load of &amp;lt;50 copies/ml with 40% and 83% achieving a CD4 count of &amp;gt;350 cells/μL and &amp;gt;200 cells/μL respectively. Conclusions A significant proportion of PLWH still present with aggressive lymphoma as an AIDS-defining event prior to HIV diagnosis, despite high levels of health education and healthcare availability. Our results appear equivalent to those for non-HIV patients with acceptable toxicity. Current Australian practice favors treating aggressive lymphomas in PLWH similarly to the HIV negative population, with the addition of concurrent ART. CD4+ T-cell-related immune reconstitution appears to recover within 6 months post-therapy. The OS of this cohort appears similar to the HIV negative population and published cohort studies (Coutinho AIDS 2013, Evens Blood 2019, Alderuccio Blood Adv 2021). Figure 1 Figure 1. Disclosures Hamad: Novartis: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Cheah: Beigene: Consultancy, Honoraria, Other: advisory; Celgene: Research Funding; AstraZeneca: Consultancy, Honoraria, Other: advisory; Loxo/Lilly: Consultancy, Honoraria, Other: advisory; TG Therapeutics: Consultancy, Honoraria, Other: advisory; AbbVie: Research Funding; Roche: Consultancy, Honoraria, Other: advisory and travel expenses, Research Funding; Janssen: Consultancy, Honoraria, Other: advisory; MSD: Consultancy, Honoraria, Other: advisory, Research Funding; Gilead: Consultancy, Honoraria, Other: advisory; Ascentage pharma: Consultancy, Honoraria, Other: advisory. Ku: Genor Biopharma: Consultancy; Antegene: Consultancy; Roche: Consultancy. </jats:sec