In-person versus electronic screening for social risks among carers of pediatric inpatients: A mixed methods randomized trial.

We aimed to compare disclosure of social risks according to self-report on an iPad versus face-to-face questions from a health professional and to explore carers' experiences of screening. This two-arm, parallel group, randomized trial was conducted from January 19, 2021, to December 17, 2021, in a public hospital pediatric ward serving a disadvantaged area of an Australian capital city. Carers of children aged ≤ 5 years admitted to the Children's Ward were eligible. The primary outcome was disclosure of social risks. The screener included nine items on food security, household utilities, transport, employment, personal and neighborhood safety, social support, housing and homelessness. Disclosure of social risks was similar between the self-completion (n = 193) and assisted-completion (n = 193) groups for all 9 items, ranging 4.1% higher for worrying about money for food (95% CI - 11.4, 3.1%) among the assisted-completion group, to 5.7% (-1.6, 13.0%) higher for unemployment among the self-completion group. In qualitative interviews, participants were positive about screening for social risks in the hospital ward setting and the majority indicated a preference for self-completion.  Conclusion: Differences in the disclosure of social risks according to self- versus assisted-completion were small, suggesting that either method could be used. Most carers expressed a preference for self- completion, which is therefore recommended as the ideal mode for such data collection for Australian pediatric inpatient settings.  Trial registration: Australia New Zealand Clinical Trial Registry ( www.anzctry.org.au ; #ACTRN12620001326987; date of registration 8 December 2020). What is Known: • Most evidence on screening of social risks in pediatric inpatient settings is from the USA. • Little is known about disclosure of social risks in countries with universal health care and social welfare. What is New: • Disclosure of social risks was similar for electronic compared with face-to-face screening. • Carers preferred electronic completion over face-to-face completion.

The Potential of Dendritic-Cell-Based Vaccines to Modulate Type 3 Innate Lymphoid Cell Populations.

Dendritic cell (DC) vaccines are a type of immunotherapy that relies on the communication of DCs with other aspects of the immune system. DCs are potent antigen-presenting cells involved in the activation of innate immune responses and education of adaptive immunity, making them ideal targets for immunotherapies. Innate lymphoid cells (ILCs) are relatively newly identified in the field of immunology and have important roles in health and disease. The studies described here explored the communications between type 3 ILCs (ILC3s) and DCs using a murine model of DC-based vaccination. Local and systemic changes in ILC3 populations following the administration of a DC vaccine were observed, and upon challenge with B16F10 melanoma cells, changes in ILC3 populations in the lungs were observed. The interactions between DCs and ILC3s should be further explored to determine the potential that their communications could have in health, disease, and the development of immunotherapies.

Neutrophils in Dendritic Cell-Based Cancer Vaccination: The Potential Roles of Neutrophil Extracellular Trap Formation.

Neutrophils have conflicting roles in the context of cancers, where they have been associated with contributing to both anti-tumor and pro-tumor responses. Their functional heterogenicity is plastic and can be manipulated by environmental stimuli, which has fueled an area of research investigating therapeutic strategies targeting neutrophils. Dendritic cell (DC)-based cancer vaccination is an immunotherapy that has exhibited clinical promise but has shown limited clinical efficacy. Enhancing our understanding of the communications occurring during DC cancer vaccination can uncover opportunities for enhancing the DC vaccine platform. There have been observed communications between neutrophils and DCs during natural immune responses. However, their crosstalk has been poorly studied in the context of DC vaccination. Here, we review the dual functionality of neutrophils in the context of cancers, describe the crosstalk between neutrophils and DCs during immune responses, and discuss their implications in DC cancer vaccination. This discussion will focus on how neutrophil extracellular traps can influence immune responses in the tumor microenvironment and what roles they may play in promoting or hindering DC vaccine-induced anti-tumor efficacy.

Murine Mast Cells That Are Deficient in IFNAR-Signaling Respond to Viral Infection by Producing a Large Amount of Inflammatory Cytokines, a Low Level of Reactive Oxygen Species, and a High Rate of Cell Death.

Mat cells (MCs) are located in the skin and mucous membranes at points where the body meets the environment. When activated, MCs release inflammatory cytokines, which help the immune system to fight viruses. MCs produce, and have receptors for interferons (IFNs), which belong to a family of cytokines recognized for their antiviral properties. Previously, we reported that MCs produced proinflammatory cytokines in response to a recombinant vesicular stomatitis virus (rVSVΔm51) and that IFNAR signaling was required to down-modulate these responses. Here, we have demonstrated that UV-irradiated rVSVΔm51 did not cause any inflammatory cytokines in either in vitro cultured mouse IFNAR-intact (IFNAR+/+), or in IFNAR-knockout (IFNAR-/-) MCs. However, the non-irradiated virus was able to replicate more effectively in IFNAR-/- MCs and produced a higher level of inflammatory cytokines compared with the IFNAR+/+ MCs. Interestingly, MCs lacking IFNAR expression displayed reduced levels of reactive oxygen species (ROS) compared with IFNAR+/+ MCs. Additionally, upon the viral infection, these IFNAR-/- MCs were found to coexist with many dying cells within the cell population. Based on our findings, IFNAR-intact MCs exhibit a lower rate of rVSVΔm51 infectivity and lower levels of cytokines while demonstrating higher levels of ROS. This suggests that MCs with intact IFNAR signaling may survive viral infections by producing cell-protective ROS mechanisms and are less likely to die than IFNAR-/- cells.

Psychological service provision in Australian Palliative Care Services.

OBJECTIVES: Psychological distress is common among palliative care patients. Despite this, little is known about the availability of psychological services to support palliative care patients within Australia. This study aimed to determine the level of psychological support services available within Australian Palliative Care Services. The study was based on a similar study in Australia by Crawford in 1999, allowing differences over time to be examined. METHODS: A 12-item online survey was distributed to adult Palliative Care Services throughout Australia from November 2021 to January 2022. Quantitative and qualitative analysis of responses was conducted, with comparisons made with the 1999 study using a 2-proportions z-test. RESULTS: Social workers were the most available professionals delivering psychological care (prevalence of 94.1%), followed by spiritual care workers (62.5%), creative therapists (43.8%), counselors (36.4%), psychiatrists (31.3%), complementary therapists (28.1%), and psychologists (25.0%). Nearly 60% of services had no access to a psychiatrist or a psychologist. The proportion of Palliative Care Services that had access to a psychiatrist, psychologist, or counselor was significantly less in 2021/22 compared to 1999, with differences of 29.4% (p = 0.002), 23.4% (p = 0.015), and 26.1% (p = 0.006), respectively. SIGNIFICANCE OF RESULTS: Lack of access to psychiatrists, psychologists, and counselors in Australian Palliative Care Services remains a significant issue and has become more prevalent since 1999. Ongoing advocacy and increased government funding to enable psychological health professionals to be readily employed in Palliative Care Services is vital.

Type I Interferon α/ß Receptor-Mediated Signaling Negatively Regulates Antiviral Cytokine Responses in Murine Bone-Marrow-Derived Mast Cells and Protects the Cells from Virus-Induced Cell Death.

Mast cells (MCs) are critical for initiating inflammatory responses to pathogens including viruses. Type I interferons (IFNs) that exert their antiviral functions by interacting with the type I IFN receptor (IFNAR) play a central role in host cellular responses to viruses. Given that virus-induced excessive toxic inflammatory responses are associated with aberrant IFNAR signaling and considering MCs are an early source of inflammatory cytokines during viral infections, we sought to determine whether IFNAR signaling plays a role in antiviral cytokine responses of MCs. IFNAR-intact, IFNAR-blocked, and IFNAR-knockout (IFNAR-/-) bone-marrow-derived MCs (BMMCs) were treated in vitro with a recombinant vesicular stomatitis virus (rVSVΔm51) to assess cytokine production by these cells. All groups of MCs produced the cytokines interleukin-6 and tumor necrosis factor-α in response to rVSVΔm51. However, production of the cytokines was lowest in IFNAR-intact cells as compared with IFNAR-/- or IFNAR-blocked cells at 20 h post-stimulation. Surprisingly, rVSVΔm51 was capable of infecting BMMCs, but functional IFNAR signaling was able to protect these cells from virus-induced death. This study showed that BMMCs produced pro-inflammatory cytokines in response to rVSVΔm51 and that IFNAR signaling was required to down-modulate these responses and protect the cells from dying from viral infection.

Characterization of the Impact of Oncolytic Vesicular Stomatitis Virus on the Trafficking, Phenotype, and Antigen Presentation Potential of Neutrophils and Their Ability to Acquire a Non-Structural Viral Protein.

Neutrophils are innate leukocytes that mount a rapid response to invading pathogens and sites of inflammation. Although neutrophils were traditionally considered responders to bacterial infections, recent advances have demonstrated that they are interconnected with both viral infections and cancers. One promising treatment strategy for cancers is to administer an oncolytic virus to activate the immune system and directly lyse cancerous cells. A detailed characterization of how the innate immune system responds to a viral-based therapy is paramount in identifying its systemic effects. This study analyzed how administering the rhabdovirus vesicular stomatitis virus (VSV) intravenously at 1 × 109 PFU acutely influenced neutrophil populations. Bone marrow, blood, lungs, and spleen were acquired three- and 24-h after administration of VSV for analysis of neutrophils by flow cytometry. Infection with VSV caused neutrophils to rapidly egress from the bone marrow and accumulate in the lungs. A dramatic increase in immature neutrophils was observed in the lungs, as was an increase in the antigen presentation potential of these cells within the spleen. Furthermore, the potential for neutrophils to acquire viral transgene-encoded proteins was monitored using a variant of VSV that expressed enhanced green fluorescent protein (GFP). If an in vitro population of splenocytes were exposed to αCD3 and αCD28, a substantial proportion of the neutrophils would become GFP-positive. This suggested that the neutrophils could either acquire more virus-encoded antigens from infected splenocytes or were being directly infected. Five different dosing regimens were tested in mice, and it was determined that a single dose of VSV or two doses of VSV administered at a 24-h interval, resulted in a substantial proportion of neutrophils in the bone marrow becoming GFP-positive. This correlated with a decrease in the number of splenic neutrophils. Two doses administered at intervals longer than 24-h did not have these effects, suggesting that neutrophils became resistant to antigen uptake or direct infection with VSV beyond 24-h of activation. These findings implicated neutrophils as major contributors to oncolytic rhabdoviral therapies. They also provide several clear future directions for research and suggest that neutrophils should be carefully monitored during the development of all oncolytic virus-based treatment regimens.

Self-administered acupressure for insomnia disorder: a pilot randomized controlled trial.

Self-administered acupressure has potential as a low-cost alternative treatment for insomnia. To evaluate the short-term effects of self-administered acupressure for alleviating insomnia, a pilot randomized controlled trial was conducted. Thirty-one subjects (mean age: 53.2 years; 77.4% female) with insomnia disorder were recruited from a community. The participants were randomized to receive two lessons on either self-administered acupressure or sleep hygiene education. The subjects in the self-administered acupressure group (n = 15) were taught to practise self-administered acupressure daily for 4 weeks. The subjects in the comparison group (n = 16) were advised to follow sleep hygiene education. The primary outcome was the Insomnia Severity Index (ISI). Other measures included a sleep diary, Hospital Anxiety and Depression Scale and Short-form Six-Dimension. The subjects in the self-administered acupressure group had a significantly lower ISI score than the subjects in the sleep hygiene education group at week 8 (effect size = 0.56, P = 0.03). However, this observed group difference did not reach a statistically significant level after Bonferroni correction. With regard to the secondary outcomes, moderate between-group effect sizes were observed in sleep onset latency and wake after sleep onset based on the sleep diary, although the differences were not significant. The adherence to self-administered acupressure practice was satisfactory, with 92.3% of the subjects who completed the lessons still practising acupressure at week 8. In conclusion, self-administered acupressure taught in a short training course may be a feasible approach to improve insomnia. Further fully powered confirmatory trials are warranted.

Eating occasions and the contribution of foods to sodium and potassium intakes in adults.

OBJECTIVE: To examine dietary Na and K intake at eating occasions in Australian adults and identify the contribution of major food sources to Na and K at different eating occasions. DESIGN: Secondary analysis of 24 h recall diet data from the Australian Health Survey (2011-2013). SETTING: Nationally representative survey in Australia. SUBJECTS: Male and female Australians aged 18-84 years (n 7818). RESULTS: Dinner contributed the greatest proportion to total daily Na intake (33 %) and K intake (35 %). Na density was highest at lunch (380 mg/MJ) and K density highest at between-meal time eating occasions (401 mg/MJ). Between-meal time eating occasions provided 20 % of daily Na intake and 26 % of daily K intake. The major food group sources of Na were different at meal times (breads and mixed dishes) compared with between-meal times (cakes, muffins, scones, cake-type desserts). The top food group sources of K at meal times were potatoes and unprocessed meat products and dishes. CONCLUSIONS: Foods which contributed to Na and K intake differed according to eating occasion. Major food sources of Na were bread and processed foods. Major food sources of K were potatoes and meat products and dishes. Public health messages that emphasise meal-based advice and diet patterns high in vegetables, fruits and unprocessed foods may also aid reduction in dietary Na intake and increase in dietary K intake.

Chinese medical students' knowledge, attitude and practice towards human papillomavirus vaccination and their intention to recommend the vaccine.

AIM: The human papillomavirus (HPV) vaccine is effective in preventing cervical cancer, but its global uptake rate in vulnerable populations is unsatisfactory. Physician's recommendation is an important determinant for vaccine uptake, but we have limited understanding on the contributing factors of physician's recommendation. This study investigated whether the knowledge, attitudes and vaccination status of medical students would affect their intention to recommend HPV vaccination. METHODS: This is a population-representative survey of medical schools in Hong Kong. RESULTS: Participants included 1022 Chinese medical students (46.9% of all in Hong Kong; 46.3% female). Better HPV-related knowledge and a more positive attitude towards HPV vaccination were important factors predicting vaccine uptake and intention to recommend. HPV vaccination status and intention to receive the vaccine were positively associated with intention to recommend among females. CONCLUSION: Better HPV-related medical education may be a feasible way to promote the HPV vaccine in regions without universal coverage. Medical students who have not received the HPV vaccine should also be encouraged to receive the vaccine.

Three-in-one protocol reduces mortality of patients with haemodynamically unstable pelvic fractures-a five year multi-centred review in Hong Kong.

PURPOSE: The mortality rate in patients with haemodynamically unstable pelvic fractures is as high as 40-60%. Despite the new advances in trauma care which are in phase in trauma centres in Hong Kong, the management of haemodynamically unstable pelvic fracture is still heterogeneous. The aim of this study is to review the results of management of haemodynamically unstable pelvic fracture patients in Hong Kong over a five year period. METHODS: This is a retrospective multi-centred cohort study of patients with haemodynamic and mechanically unstable pelvic fractures from 1 January 2010 to 31 December 2014. The primary outcome investigated is mortality of patients (including overall, 30-day, 7-day and 24-hour mortalities). RESULTS: Implementation of three-in-one pelvic damage control protocol was identified to be a significant independent predictive factor for overall, 30-day, seven-day and 24-hour mortalities. The overall in-hospital and 30-day mortality rates for patients managed with three-in-one protocol was 12.5%, while it was 11% for seven day mortality and 6% for 24 hour mortality. There were no significant differences in demographic characteristics, physiological measurements, types of pelvic fracture, severity and mechanism of injury between patients managed with or without three-in-one protocol. CONCLUSIONS: Implementation of the multidisciplinary three-in-one pelvic damage control protocol reduces mortality and therefore should be highly recommended. The results are convincing as it has eliminated the limitations of our previous single-centred trial.

Does the presence of cardiovascular disease risk factors or established disease influence the dietary intake of affected adults and their children residing in the same household? A secondary analysis of the Australian Health Survey (2011-2013).

BACKGROUND: Diet is an important contributor to risk of cardiovascular disease (CVD) and integral in management and delaying progression. Little is known however about whether increased CVD risk or established CVD has any influence on dietary intakes of Australian adults or children residing in the same household. This study aimed to determine whether the presence of CVD or CVD risk factors influences dietary intake of Australian adults and if the presence of an adult with increased CVD risk influences the dietary intake of a child living in the same household. METHODS: Data were sourced from the 2011-2013 Australian Health Survey for: (1) adults ≥18 years with risk factors or established CVD and (2) children 2-17 years residing in the same household as adults with CVD risk factors or established CVD. Selected nutrient intakes (total fat, saturated fat plus trans fat, alpha-linolenic acid, total long chain omega 3 fatty acids, fibre and sodium) collected by repeated 24 h recalls were compared to national dietary recommendations and to the intakes of all other adults and children surveyed. Standard errors of the estimates were calculated using the replicate weights method, and an alpha value of <0.05 considered statistically significant. RESULTS: Six thousand two hundred sixty five of 9435 adults surveyed were identified as having CVD risk factors or established disease and of these 1609 had a child in the same household that also contributed data in this survey. No differences were observed in adjusted mean dietary intakes between those without risk factors or established CVD and those with, except for total energy and sodium which were significantly lower in the adults with CVD risk factors and/or established disease. However sodium intakes across both groups were higher than recommended targets. There were no differences for selected nutrients between children residing with affected adults and other children surveyed. CONCLUSIONS: While intakes of Australian adults with CVD risk factors or established disease were favourable for sodium, compared to unaffected adults, there is still scope for improvement as many Australian adults, despite CVD risk, are unable to achieve targets for selected nutrients. Effective dietary behaviour change strategies and resources are urgently needed.

CONSORT to community: translation of an RCT to a large-scale community intervention and learnings from evaluation of the upscaled program.

BACKGROUND: Translation encompasses the continuum from clinical efficacy to widespread adoption within the healthcare service and ultimately routine clinical practice. The Parenting, Eating and Activity for Child Health (PEACH™) program has previously demonstrated clinical effectiveness in the management of child obesity, and has been recently implemented as a large-scale community intervention in Queensland, Australia. This paper aims to describe the translation of the evaluation framework from a randomised controlled trial (RCT) to large-scale community intervention (PEACH™ QLD). Tensions between RCT paradigm and implementation research will be discussed along with lived evaluation challenges, responses to overcome these, and key learnings for future evaluation conducted at scale. METHODS: The translation of evaluation from PEACH™ RCT to the large-scale community intervention PEACH™ QLD is described. While the CONSORT Statement was used to report findings from two previous RCTs, the REAIM framework was more suitable for the evaluation of upscaled delivery of the PEACH™ program. Evaluation of PEACH™ QLD was undertaken during the project delivery period from 2013 to 2016. RESULTS: Experiential learnings from conducting the evaluation of PEACH™ QLD to the described evaluation framework are presented for the purposes of informing the future evaluation of upscaled programs. Evaluation changes in response to real-time changes in the delivery of the PEACH™ QLD Project were necessary at stages during the project term. Key evaluation challenges encountered included the collection of complete evaluation data from a diverse and geographically dispersed workforce and the systematic collection of process evaluation data in real time to support program changes during the project. CONCLUSIONS: Evaluation of large-scale community interventions in the real world is challenging and divergent from RCTs which are rigourously evaluated within a more tightly-controlled clinical research setting. Constructs explored in an RCT are inadequate in describing the enablers and barriers of upscaled community program implementation. Methods for data collection, analysis and reporting also require consideration. We present a number of experiential reflections and suggestions for the successful evaluation of future upscaled community programs which are scarcely reported in the literature. TRIALS REGISTRATION: PEACH™ QLD was retrospectively registered with the Australian New Zealand Clinical Trials Registry on 28 February 2017 (ACTRN12617000315314).

Dietary intake of working women with children does not appear to be influenced by hours of employment: A secondary analysis of the Australian Health Survey (2011-2013).

UNLABELLED: Women with children often fulfil multiple roles of running a household, raising a family and working outside the home. Good nutrition during this time is important to optimise their performance and prevent lifestyle diseases. Women also act as nutritional gatekeepers for their family. The dual burden of paid employment and unpaid family work may be associated with time scarcity in mothers which can impact food preparation and therefore nutritional adequacy. The aim of this study was to examine the diet of women who lived with children by comparison of hours worked. METHODS: This was a secondary analysis of the Australian National Nutrition and Physical Activity Survey 2011-12. Subjects were women aged 18-65 years who resided with ≥1 child (<18 years). Women were grouped according to hours of employment: not working; working <25 h a week; and working ≥25 hours a week. Data from two 24-h dietary recalls were used to compare differences between groups in nutrient intake and proportion of energy from discretionary foods. Covariates included were age, education, smoker status, Socio-Economic Indexes for Areas (SEIFA), number of persons in household, week or weekend day of the survey and the sequence of recalls. RESULTS: Analyses included 1869 women. Dietary intakes varied minimally between groups with intakes of fibre, vitamin C, and calcium lowest in the group not working. Overall diet quality was poor with >30% of energy coming from discretionary foods in all groups. CONCLUSIONS: Usual hours of employment per week have a minimal effect on diet quality in women with children. It is likely that different factors specific to each group contribute to the poor dietary intakes and should be further investigated.

The microRNA-342-5p fosters inflammatory macrophage activation through an Akt1- and microRNA-155-dependent pathway during atherosclerosis.

BACKGROUND: Atherosclerosis is a chronic inflammatory vascular disease driven by the subendothelial accumulation of macrophages. The mechanism regulating the inflammatory response in macrophages during atherogenesis remains unclear. Because microRNAs (miRNAs) play a crucial role in cellular signaling by posttranscriptional regulation of gene expression, we studied the miRNA expression profiles during the progression of atherosclerosis. METHODS AND RESULTS: Using an miRNA real-time polymerase chain reaction array, we found that macrophage-derived miR-342-5p and miR-155 are selectively upregulated in early atherosclerotic lesions in Apoe(-/-) mice. miR-342-5p directly targets Akt1 through its 3'-untranslated region. Akt1 suppression by miR-342-5p induces proinflammatory mediators such as Nos2 and II6 in macrophages via the upregulation of miR-155. The local application of an miR-342-5p antagomir inhibits the development of atherosclerosis in partially ligated carotid arteries. In atherosclerotic lesions, the miR-342-5p antagomir upregulated Akt1 expression and suppressed the expression of miR-155 and Nos2. This reduced Nos2 expression was associated with a diminished generation of nitrotyrosine in the plaques. Furthermore, systemic treatment with an inhibitor of miR-342-5p reduced the progression of atherosclerosis in the aorta of Apoe(-/-) mice. CONCLUSIONS: Macrophage-derived miR-342-5p promotes atherosclerosis and enhances the inflammatory stimulation of macrophages by suppressing the Akt1-mediated inhibition of miR-155 expression. Therefore, targeting miR-342-5p may offer a promising strategy to treat atherosclerotic vascular disease.

Technology-supported behavior change interventions for reducing sodium intake in adults: a systematic review and meta-analysis.

The effects of technology-supported behavior change interventions for reducing sodium intake on health outcomes in adults are inconclusive. Effective intervention characteristics associated with sodium reduction have yet to be identified. A systematic review and meta-analysis were conducted, searching randomized controlled trials (RCTs) published between January 2000 and April 2023 across 5 databases (PROSPERO: CRD42022357905). Meta-analyses using random-effects models were performed on 24-h urinary sodium (24HUNa), systolic blood pressure (SBP), and diastolic blood pressure (DBP). Subgroup analysis and meta-regression of 24HUNa were performed to identify effective intervention characteristics. Eighteen RCTs involving 3505 participants (51.5% female, mean age 51.6 years) were included. Technology-supported behavior change interventions for reducing sodium intake significantly reduced 24HUNa (mean difference [MD] -0.39 gm/24 h, 95% confidence interval [CI] -0.50 to -0.27; I2 = 24%), SBP (MD -2.67 mmHg, 95% CI -4.06 to -1.29; I2 = 40%), and DBP (MD -1.39 mmHg, 95% CI -2.31 to -0.48; I2 = 31%), compared to control conditions. Interventions delivered more frequently (≤weekly) were associated with a significantly larger effect size in 24HUNa reduction compared to less frequent interventions (>weekly). Other intervention characteristics, such as intervention delivery via instant messaging and participant-family dyad involvement, were associated with larger, albeit non-significant, effect sizes in 24HUNa reduction when compared to other subgroups. Technology-supported behavior change interventions aimed at reducing sodium intake were effective in reducing 24HUNa, SBP, and DBP at post-intervention. Effective intervention characteristics identified in this review should be considered to develop sodium intake reduction interventions and tested in future trials, particularly for its long-term effects.

Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges.

The rapid development and deployment of vaccines following the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to have saved millions of lives. Despite their immense success, there remains a need for next-generation vaccination approaches for SARS-CoV-2 and future emerging coronaviruses and other respiratory viruses. Here we utilized a Newcastle Disease virus (NDV) vectored vaccine expressing the ancestral SARS-CoV-2 spike protein in a pre-fusion stabilized chimeric conformation (NDV-PFS). When delivered intranasally, NDV-PFS protected both Syrian hamsters and K18 mice against Delta and Omicron SARS-CoV-2 variants of concern. Additionally, intranasal vaccination induced robust, durable protection that was extended to 6 months post-vaccination. Overall, our data provide evidence that NDV-vectored vaccines represent a viable next-generation mucosal vaccination approach.

Effects of microbiome-based interventions on neurodegenerative diseases: a systematic review and meta-analysis.

Neurodegenerative diseases (NDDs) are characterized by neuronal damage and progressive loss of neuron function. Microbiome-based interventions, such as dietary interventions, biotics, and fecal microbiome transplant, have been proposed as a novel approach to managing symptoms and modulating disease progression. Emerging clinical trials have investigated the efficacy of interventions modulating the GM in alleviating or reversing disease progression, yet no comprehensive synthesis have been done. A systematic review of the literature was therefore conducted to investigate the efficacy of microbiome-modulating methods. The search yielded 4051 articles, with 15 clinical trials included. The overall risk of bias was moderate in most studies. Most microbiome-modulating interventions changed the GM composition. Despite inconsistent changes in GM composition, the meta-analysis showed that microbiome-modulating interventions improved disease burden (SMD, - 0.57; 95% CI - 0.93 to - 0.21; I2 = 42%; P = 0.002) with a qualitative trend of improvement in constipation. However, current studies have high methodological heterogeneity and small sample sizes, requiring more well-designed and controlled studies to elucidate the complex linkage between microbiome, microbiome-modulating interventions, and NDDs.

Novel Quantitative Contrast Sensitivity Function Enhances the Prediction of Treatment Outcome and Recurrence in Amblyopia.

Purpose: Although effective amblyopia treatments are available, treatment outcome is unpredictable, and the condition recurs in up to 25% of the patients. We aimed to evaluate whether a large-scale quantitative contrast sensitivity function (CSF) data source, coupled with machine learning (ML) algorithms, can predict amblyopia treatment response and recurrence in individuals. Methods: Visual function measures from traditional chart vision acuity (VA) and novel CSF assessments were used as the main predictive variables in the models. Information from 58 potential predictors was extracted to predict treatment response and recurrence. Six ML methods were applied to construct models. The SHapley Additive exPlanations was used to explain the predictions. Results: A total of 2559 consecutive records of 643 patients with amblyopia were eligible for modeling. Combining variables from VA and CSF assessments gave the highest accuracy for treatment response prediction, with the area under the receiver operating characteristic curve (AUC) of 0.863 and 0.815 for outcome predictions after 3 and 6 months, respectively. Variables from the VA assessment alone predicted the treatment response, with AUC values of 0.723 and 0.675 after 3 and 6 months, respectively. Variables from the CSF assessment gave rise to an AUC of 0.909 for recurrence prediction compared to 0.539 for VA assessment alone, and adding VA variables did not improve predictive performance. The interocular differences in CSF features are significant contributors to recurrence risk. Conclusions: Our models showed CSF data could enhance treatment response prediction and accurately predict amblyopia recurrence, which has the potential to guide amblyopia management by enabling patient-tailored decision making.

Quantitative measurement of interocular suppression in anisometropic amblyopia: a case-control study.

OBJECTIVE: The aims of this study were to assess (1) the relationship between interocular suppression and visual function in patients with anisometropic amblyopia, (2) whether suppression can be simulated in matched controls using monocular defocus or neutral density filters, (3) the effects of spectacle or rigid gas-permeable contact lens correction on suppression in patients with anisometropic amblyopia, and (4) the relationship between interocular suppression and outcomes of occlusion therapy. DESIGN: Case-control study (aims 1-3) and cohort study (aim 4). PARTICIPANTS: Forty-five participants with anisometropic amblyopia and 45 matched controls (mean age, 8.8 years for both groups). METHODS: Interocular suppression was assessed using Bagolini striated lenses, neutral density filters, and an objective psychophysical technique that measures the amount of contrast imbalance between the 2 eyes that is required to overcome suppression (dichoptic motion coherence thresholds). Visual acuity was assessed using a logarithm minimum angle of resolution tumbling E chart and stereopsis using the Randot preschool test. MAIN OUTCOME MEASURES: Interocular suppression assessed using dichoptic motion coherence thresholds. RESULTS: Patients exhibited significantly stronger suppression than controls, and stronger suppression was correlated significantly with poorer visual acuity in amblyopic eyes. Reducing monocular acuity in controls to match that of cases using neutral density filters (luminance reduction) resulted in levels of interocular suppression comparable with that in patients. This was not the case for monocular defocus (optical blur). Rigid gas-permeable contact lens correction resulted in less suppression than spectacle correction, and stronger suppression was associated with poorer outcomes after occlusion therapy. CONCLUSIONS: Interocular suppression plays a key role in the visual deficits associated with anisometropic amblyopia and can be simulated in controls by inducing a luminance difference between the eyes. Accurate quantification of suppression using the dichoptic motion coherence threshold technique may provide useful information for the management and treatment of anisometropic amblyopia. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found after the references.