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BackgroundMaintaining durable immunity following vaccination represents a major challenge, but whether mRNA booster vaccination improves durability is unknown.MethodsWe measured antibody responses in 55 healthy adults, who received a booster dose of the Pfizer-BioNTech or Moderna vaccine against SARS-CoV-2 and calculated the half-life of the antibody titers. We also measured memory B and T cell responses in a subset of 28 participants. In 13 volunteers who received a second booster vaccine, we measured serum antibody titers and memory B and T cell responses.ResultsThe booster (third immunization) dose at 6 to 10 months increased the half-life of the serum-neutralizing antibody (nAb) titers to 76 days from 56 to 66 days after the primary 2-dose vaccination. A second booster dose (fourth immunization) a year after the primary vaccination further increased the half-life to 88 days. However, despite this modestly improved durability in nAb responses against the ancestral (WA.1) strain, there was a loss of neutralization capacity against the Omicron subvariants BA.2.75.2, BQ.1.1, and XBB.1.5 (48-, 71-, and 66-fold drop in titers, respectively, relative to the WA.1 strain). Although only 45% to 65% of participants demonstrated a detectable nAb titer against the newer variants after the booster (third dose), the response declined to below the detection limit in almost all individuals by 6 months. In contrast, booster vaccination induced antigen-specific memory B and T cells that persisted for at least 6 months.ConclusionThe durability of serum antibody responses improves only marginally following booster immunizations with the Pfizer-BioNTech or Moderna mRNA vaccines.

People living with HIV (PLH) experience higher rates of HPV infection as well as an increased risk of HPV-related disease, including malignancies. Although they are considered a high-priority group for HPV vaccination, there are limited data regarding the long-term immunogenicity and efficacy of HPV vaccines in this population. Seroconversion rates and geometric mean titers elicited by vaccination are lower in PLH compared to immunocompetent participants, especially in individuals with CD4 counts below 200 cells/mm3 and a detectable viral load. The significance of these differences is still unclear, as a correlate of protection has not been identified. Few studies have focused on demonstrating vaccine efficacy in PLH, with variable results depending on the age at vaccination and baseline seropositivity. Although waning humoral immunity for HPV seems to be more rapid in this population, there is evidence that suggests that seropositivity lasts at least 2–4 years following vaccination. Further research is needed to determine the differences between vaccine formulations and the impact of administrating additional doses on durability of immune protection.

Abstract Background Since the introduction of highly active antiretroviral therapy, asymptomatic and mild neurocognitive impairment are the main clinical manifiestations of HIV associated neurocognitive disorders (HAND), compromising adherence to treatment, daily performance, quality of life, and even increasing the risk of mortality. We do not have validated screening tools for early detection of HAND applicable to the routine medical visit. The Montreal Cognitive Assessment test (MoCA) is a simple questionnaire used in Alzheimer’s disease, but its utility as a screening tool for HAND remains controversial. Methods We designed a prospective study to establish MoCA´s usefulness as a rapid and sensitive tool for the detection of HAND, compared with a gold-standard test (GST) that includes Mini-mental State Examination (MMSE) and a battery of assays that evaluate several neurological domains. Adult patients with HIV infection attending our institution were included. The MoCA test was performed by infectious diseases specialists, and the GST by neurologists. History of recent stroke, neurological disease, opportunistic central nervous system infection, major depression, schizophrenia, bipolar disorder, substance abuse or dependence on alcohol, were exclusion criteria. We analized demographic and clinical variables. Results Fifty HIV-infected patients were enrolled, 94% males, with a mean age of 45.6 years (range 20–75), and an average of 14.8 years of education (range 3–26). The mean CD4 cell count was 596 cells/ml (range 65–1130), and 70% of the patients had undetectable viral load (≤20 copies/mL) at the time of the evaluation. Compared with GST, MoCA had a sensibility (S) of 94.12% (CI 71.3–99.8), specificity (E) 78.79% (CI 61.09–91.02), positive predictive value (PPV) 69.57% (CI 47–86.79) and negative predictive value (NPV) 96.3 (CI 81–99.9). In contrast, the MMSE presented S 11.76% (CI 1.46–36.44), E 100% (CI 89.4–100), PPV 100% (CI 15.8–100) and NPV 68.75% (CI 53.7–81.3). Cohen’s kappa coefficient between MoCA and GST was 0.67 (95% CI 0.46–0.87), reflecting an adequate agreement. Conclusion MoCA’s performance as a screening test was adequate compared with GST and far superior to MMSE for early detection of HAND. Although specifity could be optimized, MoCA test remains a valuable screening tool in the routine medical visit in our HIV population. Disclosures All authors: No reported disclosures.

Despite the fact that astrocytes are the most abundant glial cells, critical for brain function, few studies have dealt with their possible role in neurodegenerative diseases like Parkinson’s disease (PD). This article explores relevant evidence on the involvement of astrocytes in experimental PD neurodegeneration from a molecular signaling perspective. For a long time, astrocytic proliferation was merely considered a byproduct of neuroinflammation, but by the time being, it is clear that astrocytic dysfunction plays a far more important role in PD pathophysiology. Indeed, ongoing experimental evidence suggests the importance of astrocytes and dopaminergic neurons’ cross-linking signaling pathways. The Wnt-1 (wingless-type MMTV integration site family, member 1) pathway regulates several processes including neuron survival, synapse plasticity, and neurogenesis. In PD animal models, Frizzled (Fzd) neuronal receptors’ activation by the Wnt-1 normally released by astrocytes following injuries leads to β-catenin-dependent gene expression, favoring neuron survival and viability. The transient receptor potential vanilloid 1 (TRPV1) capsaicin receptor also participates in experimental PD genesis. Activation of astrocyte TRPV1 receptors by noxious stimuli results in reduced inflammatory response and increased ciliary neurotrophic factor (CNTF) synthesis, which enhances neuronal survival and differentiation. Another major pathway involves IκB kinase (IKK) downregulation by ARL6ip5 (ADP-ribosylation-like factor 6 interacting protein 5, encoded by the cell differentiation-associated, JWA, gene). Typically, IKK releases the proinflammatory NF-κB (nuclear factor kappa-light-chain-enhancer of activated B cells) molecule from its inhibitor. Therefore, by downregulating NF-κB inhibitor, ARL6ip5 promotes an anti-inflammatory response. The evidence provided by neurotoxin-induced PD animal models guarantees further research on the neuroprotective potential of normalizing astrocyte function in PD.

Background: Family care of frail elderly people has been linked to significant negative consequences for caregivers' mental health. Although outcome variables such as burden and depression have been widely analyzed in this population, guilt, an emotion frequently observed in caregivers, has not received sufficient attention in the research literature. Methods: Face-to-face interviews were carried out with 288 dementia caregivers. Guilt was measured using the Caregiver Guilt Questionnaire (CGQ). Results: Using principal components analysis, 22 items were retained and five factors were obtained which explained 59.25% of the variance. These factors were labeled: guilt about doing wrong by the care recipient, guilt about not rising to the occasion as caregivers, guilt about self-care, guilt about neglecting other relatives, and guilt about having negative feelings towards other people. Acceptable reliability indexes were found, and significant associations between the CGQ and its factors and the Zarit Burden Interview guilt factor were also found. Caregivers with higher scores on the CGQ also scored higher in depression, anxiety, frequency and appraisal of behavioral problems. Negative associations between the CGQ and its factors and frequency of/and satisfaction with leisure and social support were also found. Being female and caring for a parent were associated with higher scores on the CGQ. Conclusions: Feelings of guilt are significantly related to caregiver distress. The CGQ may be a useful measure for acknowledging feelings of guilt in caregivers; moreover, it can be used as an outcome variable for psychoeducational interventions aimed at reducing caregiver distress.

Respiratory syncytial virus (RSV) is an important cause of hospitalization and death in infants worldwide. Most RSV deaths occur in developing countries, where burden and risk factors for life-threatening illness are unclear. We defined the burden of life-threatening (O(2) saturation [O(2) sat] ≤ 87%) and fatal RSV infection, and characterized risk factors for life-threatening disease in hospitalized children. Special emphasis was placed on studying the impact of dietary habits during pregnancy. We hypothesized that dietary preferences, differing from those of our remote ancestors, would negatively impact children's pulmonary health. For instance, a diet rich in carbohydrates is a signature of recent millennia and typical of low-income populations, heavily burdened by life-threatening RSV disease. Prospective study in a catchment population of 56,560 children under 2 years of age during the RSV season in Argentina. All children with respiratory signs and O(2) sat less than 93% on admission were included. Among 1,293 children with respiratory infections, 797(61.6%) were infected with RSV: 106 of these had life-threatening disease; 1.9 per 1,000 children (95% confidence interval [CI], 1.5-2.2/1,000) under 24 months. A total of 22 hospitalized children died (9 RSV(+)), 26 died at home due to acute respiratory infection (14 attributed to RSV); all were under 12 months old. The annual attributable mortality rate for RSV was 0.7 per 1,000 infants (95% CI, 0.4-1.1/1,000). Life-threatening disease was dose-dependently associated with carbohydrate ingestion during pregnancy (adjusted odds ratio from 3.29 [95% CI, 1.15-9.44] to 7.36 [95% CI, 2.41-22.5] versus the lowest quartile). Life-threatening and fatal RSV infections are a heavy burden on infants in the developing world. Diets rich in carbohydrates during pregnancy are associated with these severe outcomes.

The number of studies aimed at analyzing caregiving distress among carers of people with dementia has grown exponentially in recent years. The study of variables that may help reduce the impact of caregiving demands on the health of caregivers is an issue of special interest for researchers. Self-efficacy is one of these variables. Perceived self-efficacy has been described as the subjective belief that one can organize and execute courses of action to manage given situations. Higher self-efficacy expectations regarding the caregiver's own ability to handle caregiving challenges have been significantly related to lower scores on burden, anger, anxiety and depression, even after controlling for objective stressors.