The role of the social sciences and humanities in pandemic preparedness responses: insights gained from COVID-19, HIV and AIDS and related epidemics.

The COVID-19 pandemic, particularly from 2020 to mid-2022, debilitated the management of the HIV epidemic in Africa. The multiple effects included well-documented HIV service interruptions, curtailment of HIV prevention programmes, the associated marked increase in both the risk for HIV infection among key populations and vulnerability of sub-populations (e.g. adolescent girls and young women) who are the focus of these programmes and - as importantly but less well-documented - the diverse negative socio-economic effects that accentuate HIV risk and vulnerability generally (e.g. loss of earnings, gender-based violence, stigma, police harassment of people during "lockdowns"). The global biomedical response to COVID-19 was necessary and remarkable for mitigating the bio-physical impacts of the pandemic (e.g. wide-spread surveillance coupled with rapid updates on the epidemiology of infections, rapid development of vaccines and revisions of treatment). However, drawing upon the widespread criticisms of state responses to the socio-economic effects of the COVID-19 pandemic and of "lockdowns" themselves, this article elaborates a core argument within those criticisms, namely that key lessons learnt during the HIV and AIDS and other pandemics were ignored, at least during the early stages of COVID-19. Our critique is that better integration of the social sciences and humanities in responses to pandemics can counter the reflex tendency to uncritically adopt a biomedical paradigm and, more importantly, to enable consideration of the social determinants of health in pandemic responses. At root, we re-assert a key value of 'integrated' interventions, namely the accommodation of context-sensitive considerations in the formulation of strategies, policies, plans and programme designs.

EULAR recommendations for the management of antiphospholipid syndrome in adults.

The objective was to develop evidence-based recommendations for the management of antiphospholipid syndrome (APS) in adults. Based on evidence from a systematic literature review and expert opinion, overarching principles and recommendations were formulated and voted. High-risk antiphospholipid antibody (aPL) profile is associated with greater risk for thrombotic and obstetric APS. Risk modification includes screening for and management of cardiovascular and venous thrombosis risk factors, patient education about treatment adherence, and lifestyle counselling. Low-dose aspirin (LDA) is recommended for asymptomatic aPL carriers, patients with systemic lupus erythematosus without prior thrombotic or obstetric APS, and non-pregnant women with a history of obstetric APS only, all with high-risk aPL profiles. Patients with APS and first unprovoked venous thrombosis should receive long-term treatment with vitamin K antagonists (VKA) with a target international normalised ratio (INR) of 2-3. In patients with APS with first arterial thrombosis, treatment with VKA with INR 2-3 or INR 3-4 is recommended, considering the individual's bleeding/thrombosis risk. Rivaroxaban should not be used in patients with APS with triple aPL positivity. For patients with recurrent arterial or venous thrombosis despite adequate treatment, addition of LDA, increase of INR target to 3-4 or switch to low molecular weight heparin may be considered. In women with prior obstetric APS, combination treatment with LDA and prophylactic dosage heparin during pregnancy is recommended. In patients with recurrent pregnancy complications, increase of heparin to therapeutic dose, addition of hydroxychloroquine or addition of low-dose prednisolone in the first trimester may be considered. These recommendations aim to guide treatment in adults with APS. High-quality evidence is limited, indicating a need for more research.

CD3 limits the efficacy of TCR gene therapy in vivo.

The function of T-cell receptor (TCR) gene modified T cells is dependent on efficient surface expression of the introduced TCR α/ß heterodimer. We tested whether endogenous CD3 chains are rate-limiting for TCR expression and antigen-specific T-cell function. We show that co-transfer of CD3 and TCR genes into primary murine T cells enhanced TCR expression and antigen-specific T-cell function in vitro. Peptide titration experiments showed that T cells expressing introduced CD3 and TCR genes recognized lower concentration of antigen than T cells expressing TCR only. In vivo imaging revealed that TCR+CD3 gene modified T cells infiltrated tumors faster and in larger numbers, which resulted in more rapid tumor elimination compared with T cells modified by TCR only. After tumor clearance, TCR+CD3 engineered T cells persisted in larger numbers than TCR-only T cells and mounted a more effective memory response when rechallenged with antigen. The data demonstrate that provision of additional CD3 molecules is an effective strategy to enhance the avidity, anti-tumor activity and functional memory formation of TCR gene modified T cells in vivo.

Specificity for the tumor-associated self-antigen WT1 drives the development of fully functional memory T cells in the absence of vaccination.

Recently, vaccines against the Wilms Tumor antigen 1 (WT1) have been tested in cancer patients. However, it is currently not known whether physiologic levels of WT1 expression in stem and progenitor cells of normal tissue result in the deletion or tolerance induction of WT1-specific T cells. Here, we used an human leukocyte antigen-transgenic murine model to study the fate of human leukocyte antigen class-I restricted, WT1-specific T cells in the thymus and in the periphery. Thymocytes expressing a WT1-specific T-cell receptor derived from high avidity human CD8 T cells were positively selected into the single-positive CD8 population. In the periphery, T cells specific for the WT1 antigen differentiated into CD44-high memory phenotype cells, whereas T cells specific for a non-self-viral antigen retained a CD44(low) naive phenotype. Only the WT1-specific T cells, but not the virus-specific T cells, displayed rapid antigen-specific effector function without prior vaccination. Despite long-term persistence of WT1-specific memory T cells, the animals did not develop autoimmunity, and the function of hematopoietic stem and progenitor cells was unimpaired. This is the first demonstration that specificity for a tumor-associated self-antigen may drive differentiation of functionally competent memory T cells.

Engaging trainees in shaping the future of health policy.

This paper presents an analysis of the views and ideas generated at a recent health policy discussion for doctors in training. This provides an illustration of the creativity and enthusiasm that trainees can bring to the policy sphere by providing unique insights and a fresh perspective.

The promiscuous receptor.

OBJECTIVE: To determine the effectiveness of vitamin D therapy in patients with asymptomatic, prostate-specific antigen (PSA)-progression of prostate cancer. PATIENTS AND METHODS: Twenty-six patients with locally advanced or metastatic prostate cancer were treated with vitamin D. Vitamin D therapy was discontinued on disease progression as assessed by symptoms or serum PSA increase. The response to therapy was judged from changes in PSA level from the pretreatment baseline to 3 months after starting vitamin D therapy. RESULTS: Of the 26 patients, five (20%) responded to vitamin D; the mean (range) reduction in PSA level was 45.3 (15.9-95.1)%, and mean duration of response was 4-5 months. Patients in whom the PSA level was stabilized, but not reduced, after vitamin D treatment had a duration of response of up to 36 months. Treatment was well tolerated and was not associated with elevation of serum calcium levels. There was no significant correlation between response to therapy and stage of disease, Gleason grade, previous treatments or PSA level at diagnosis or initiation of vitamin D therapy. CONCLUSION: Vitamin D therapy is an effective and well tolerated treatment for patients with asymptomatic progressive prostate cancer, and is a useful addition to the therapeutic options.

Autism and social anxiety in children with sex chromosome trisomies: an observational study.

Background: Recent studies suggest that an extra sex chromosome increases the risk of both autism and social anxiety, but it unclear whether these risks are specific to particular karyotypes. Methods: We considered diagnostic data from an online psychiatric assessment (DAWBA - The Development and Well-Being Assessment) and questionnaire responses completed by parents of children with 47,XXX (N = 29), 47,XXY (N = 28) and 47,XYY (N = 32) karyotypes. Analysis focused mainly on 54 children who were diagnosed prenatally or on the basis of other medical concerns in childhood (Low Bias subgroup), to minimise ascertainment bias. Results: Children with symptoms of autism who fell short of meeting the Diagnostic and Statistical Manual of Mental Disorders (DSM)-IV criteria were coded as cases of Pervasive Developmental Disorder Not Otherwise Specified (PDDNOS). The odds ratio of autism or PDDNOS in the Low Bias group was computed relative to gender-specific population norms. This gave log odds ratio (95% confidence interval) of 5.56 (4.25 - 6.88) for XXX girls; 4.00 (2.66 - 5.33) for XXY boys; and 4.60 (3.46 - 5.74) for XYY boys. Despite this elevated risk, most children had no autistic features. A diagnosis of DSM-IV Social Phobia was rare, though, in line with prediction, all three Low Bias cases with this diagnosis had 47,XXY karyotype. All three trisomy groups showed increased risk of milder symptoms of social anxiety. Conclusions: An increased risk of autism was found in girls with 47,XXX karyotype, as well as in boys with 47,XXY or 47,XYY. Symptoms of social anxiety were increased in all three karyotypes. There was wide variation in psychiatric status of children with the same karyotype, suggesting that an extra sex chromosome affects developmental stability in a non-specific way, with a diverse range of possible phenotypes.

Faith-based intervention in depression, anxiety, and other mental disturbances.

OBJECTIVE: To determine if the effects of using the Steps to Freedom would be beneficial for a group of individuals who attended a Christian Conference. METHODS: A user-friendly 12-item questionnaire was used to monitor the outcomes of Steps to Freedom addressing six symptom/behavioral problems and six function areas. In addition, the Symptom Checklist-90 R (SCL-90-R) questionnaire was employed to document the validity of the shorter questionnaire. The questionnaires were completed before and after the administration of the Steps to Freedom. The Wilcoxon matched pairs test was used to measure the significance of the findings for the 12-item questionnaire. RESULTS: Thirty-three clients who went through the Steps to Freedom showed statistically significant improvement (P < or = 0.005) at 3 to 4 months in all symptom/behavior categories (items 1-6). All function areas (items 7-12) also demonstrated statistically significant improvement (P < or = 0.05). A comparison group who did not attend the conference or receive counseling showed no significant changes during the same period. CONCLUSIONS: These significant preliminary findings need to be confirmed by additional studies. Steps to Freedom model prayers, used by individual patients personally and/or with a counselor, could expand the care and hopefully lower the cost of mental illness.

Overview of the 2016 South African Health Review.

The Global Report on Urban Health: Equitable, Healthier Cities for Sustainable Development, issued in March 2016 by the World Health Organization and the United Nations Human Settlements Programme (UN-Habitat), emphasises the need for enhanced governance and leadership to achieve universal health coverage and the Sustainable Development Goals. Noting that a healthy population forms the foundation for 'sustainable economic growth, social stability, and full realisation of human potential', the report presents 'practical, proven solutions for working across sectors to tackle these … health challenges', and includes examples of such successes in South Africa.

Evaluación de la digestibilidad in vitro de un sustituto lácteo fabricado con harinas no precocidas / In vitro digestibility of a milk substitute fabricated with uncooked flours

Los sustitutos lácteos son utilizados en el desayuno de los beneficiarios del Programa de alimentación Escolar de la Junta Nacional de Auxilio Escolar y Becas en Chile. Los ingredientes principales de los sustitutos lácteos son leche, azúcar y harinas de cereales y las bases técnicas para fabricar estos productos estipulan además de sus proporciones que las harinas utilizadas deben estar precocidas lo que se evalúa determinando el grado de generalización de los almidones en cual debe ser mínimo de 92 por ciento. En la actualidad se ha presentado al Programa un nuevo tipo de sustituto lácteo de menor costo, formulado con harinas no precocidas y que contiene un preparado enzimático asegurándose por parte del fabricante que bajo las condiciones de reconstitución por él indicadas (85ºC y 5 min de reposo) se lograría la precocción de las harinas. El objetivo del presenta trabajo fue evaluar la digestibilidad in vitro, el efecto del preparado enzimático incorporado (tamaño molecular de almidón y equivalente de dextrosa) y el grado de gelatinización en este producto (SLE) reconstituído bajo diferentes temperaturas y tiempos de reposo. Como testigo se utilizó el mismo sustituto lácteo pero sin la incorporación del preparado enzimatico. A 85ºC y 5 min. de reposo DV para SLE fue 93,8 por ciento. a temperaturas <85ºC y 5 min, DV disminuyó significativamente (p>0,05) a 85 por ciento (75ºC), 82,2 por ciento (50ºC), 33,0 por ciento (40ºC) y 41,4 por ciento (20ºC). DV aumentó significativamente al aumentar el tiempo de reposo a 30 min. sólo para temperaturas >60ºC. Se observó que 85ºC/min el presente enzimático ha alcanzado un 92,1 por ciento de su capacidad hidrolítica potencial. El grado de gelatinización (GG) de SLE varió entre 42,6 por ciento (40ºC) y 93,8 por ciento (85ºC) para 5 min. de reposo, valores que aumentaron al dejar reposar por 30 minutos. El producto testigo mostró valores similares de DV y GG a SLE para todas las condiciones evaluadas. Se concluye que tanto SLE como el testigo presentan una buena digestibilidad in vitro y grado de gelatinización al reconstruir a 85ºC/5 min. Estos resultados indicarían que no es necesario precocer las harinas si se utilizan condiciones de preparación como las señaladas y que la incorporación de enzima cumpliría el objetivo de mejorar características físico químicas como la viscosidad del producto preparado