Miscarriage and stillbirth following maternal Zika virus infection in nonhuman primates.

Zika virus (ZIKV) infection is associated with congenital defects and pregnancy loss. Here, we found that 26% of nonhuman primates infected with Asian/American ZIKV in early gestation experienced fetal demise later in pregnancy despite showing few clinical signs of infection. Pregnancy loss due to asymptomatic ZIKV infection may therefore be a common but under-recognized adverse outcome related to maternal ZIKV infection

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Characteristics and outcomes of patients requiring unplanned transfer from subacute to acute care

The study aims to identify the reasons for, and outcomes from, unplanned transfers from subacute care to acute care. A retrospective patient record review of patients requiring unplanned transfer from subacute to an acute care emergency department (ED) from 1 July 2008 to 30 June 2009 was undertaken. Data collected included patient demographics, clinical characteristics in preceding transfer, and on ED arrival and outcome data. There were 136 patients included in the study with a median age of 81 years. The most common reasons for transfer were respiratory problems and altered conscious state. In the 24&thinsp;h preceding transfer, 92.6% of patients had &ge;&thinsp;1 physiological abnormality and 10.3% of patients had no physiological parameters documented. On ED arrival, 75% of patients had physiological abnormalities. Hospital admission occurred in 75% of patients and the inpatient mortality rate was 14.7%. Factors associated with inpatient mortality were tachypnoea and severe hypoxaemia in 24&thinsp;h preceding transfer and tachypnoea, hypoxaemia, hypoxaemia, severe hypoxaemia and hypothermia on ED arrival. Patients requiring unplanned transfer had higher inpatient mortality than older hospital users. Reasons for unplanned transfer reflect known predictors of in-hospital adverse events so predictive use of physiological data and patient characteristics might optimize patient safety.<br /

Emerging themes in dietetic competency [Conference Abstract]

Determining entry level competency of new graduates, as they transition from university to practice is not always black and white. Holistic competency emerges as acculturation and experience develops in the workplace. This project, funded by the Dietitians Association Australia (DAA), aimed to develop tools to guide the assessment process. Range variable statements and evidence guides were developed to inform the assessment of DAA Entry Level Competency Standards (ELCS) at university and to define the core fields of study required in Australian university curricula for university accreditation and international benchmarking purposes. Range variables contextualise competency by defining the boundaries for competency and the associated performance criteria. Evidence guides provide the range of contexts and critical aspects of competency which would usually be assessed together. Core fields of study defi ne the underpinning knowledge and skills required in the curriculum to achieve competency. Draft range variable statements and evidence guides were developed against each of the units and elements of the ELCS. Two rounds of consultation occurred with the fourteen Australian universities undertaking dietetic education and the project management committee, via teleconference and email. Core fi elds of study were informed by these consultations, as well as interviews of new graduates about core activities undertaken in their workplace. The final versions of these documents were presented to the project management committee, the Australian Dietetic Council and the DAA Board to be integrated into the DAA Accreditation Manual and website information

Effects of small-volume soccer and vibration training on body composition, aerobic fitness, and muscular PCr kinetics for inactive women aged 20–45

Purpose: The present study investigated the effects of 16 weeks of small-volume, small-sided soccer training soccer group (SG, n = 13) and oscillating whole-body vibration training vibration group (VG, n = 17) on body composition, aerobic fitness, and muscle PCr kinetics in healthy inactive premenopausal women in comparison with an inactive control group (CO, n = 14). Methods: Training for SG and VG consisted of twice-weekly 15-min sessions with average heart rates (HRs) of ∼155 and 90 bpm respectively. Pre- and post-measurements of body composition (DXA), phosphocreatine (PCr) on- and off-kinetics, and HR measurements during standardised submaximal exercise were performed. Results: After 16 weeks of training in SG, fat percentage was lowered (p = 0.03) by 1.7% ± 2.4% from 37.5% ± 6.9% to 35.8% ± 6.2% and the PCr decrease in the quadriceps during knee-extension ramp exercise was attenuated (4% ± 8%, p = 0.04), with no changes in VG or CO (time-group effect: p = 0.03 and p = 0.03). Submaximal exercise HR was also reduced in SG after 16 weeks of training (6% ± 5% of HRmax, p = 0.01). Conclusion: Short duration soccer training for 16 weeks appears to be sufficient to induce favourable changes in body composition and indicators of aerobic fitness and muscle oxidative capacity in untrained premenopausal women