Virtual Reality and Serious Videogame-Based Instruments for Assessing Spatial Navigation in Alzheimer's Disease: A Systematic Review of Psychometric Properties.

Over the past decade, research using virtual reality and serious game-based instruments for assessing spatial navigation and spatial memory in at-risk and AD populations has risen. We systematically reviewed the literature since 2012 to identify and evaluate the methodological quality and risk of bias in the analyses of the psychometric properties of VRSG-based instruments. The search was conducted primarily in July-December 2022 and updated in November 2023 in eight major databases. The quality of instrument development and study design were analyzed in all studies. Measurement properties were defined and analyzed according to COSMIN guidelines. A total of 1078 unique records were screened, and following selection criteria, thirty-seven studies were analyzed. From these studies, 30 instruments were identified. Construct and criterion validity were the most reported measurement properties, while structural validity and internal consistency evidence were the least reported. Nineteen studies were deemed very good in construct validity, whereas 11 studies reporting diagnostic accuracy were deemed very good in quality. Limitations regarding theoretical framework and research design requirements were found in most of the studies. VRSG-based instruments are valuable additions to the current diagnostic toolkit for AD. Further research is required to establish the psychometric performance and clinical utility of VRSG-based instruments, particularly the instrument development, content validity, and diagnostic accuracy for preclinical AD screening scenarios. This review provides a straightforward synthesis of the state of the art of VRSG-based instruments and suggests future directions for research.

The International Fragile X Premutation Registry: building a resource for research and clinical trial readiness.

FMR1 premutation cytosine-guanine-guanine repeat expansion alleles are relatively common mutations in the general population that are associated with a neurodegenerative disease (fragile X-associated tremor/ataxia syndrome), reproductive health problems and potentially a wide range of additional mental and general health conditions that are not yet well-characterised. The International Fragile X Premutation Registry (IFXPR) was developed to facilitate and encourage research to better understand the FMR1 premutation and its impact on human health, to facilitate clinical trial readiness by identifying and characterising diverse cohorts of individuals interested in study participation, and to build community and collaboration among carriers, family members, researchers and clinicians around the world. Here, we describe the development and content of the IFXPR, characterise its first 747 registrants from 32 countries and invite investigators to apply for recruitment support for their project(s). With larger numbers, increased diversity and potentially the future clinical characterisation of registrants, the IFXPR will contribute to a more comprehensive and accurate understanding of the fragile X premutation in human health and support treatment studies.

Cactus cladodes for dairy goats: what is the best fiber source?

This study evaluated the effect of different fiber sources supplied with cactus cladodes in diets on the intake and digestibility of nutrients, ingestive behavior, milk yield, and composition of dairy goats. The fiber sources were corn silage, sorghum silage, Digitaria pentzii Stent. hay, and sugarcane bagasse. Twelve Saanen goats with an average weight of 48.9 ± 7.3 kg and average production of 2.8 ± 0.7 kg of milk/day were assigned in three simultaneous 4 × 4 Latin squares (four animals, four treatments, and four experimental periods). There was no difference between the fiber sources for intake (P > 0.05) of dry matter (2.58 kg/day), organic matter (2.30 kg/day), crude protein (0.385 kg/day), neutral detergent fiber (0.895 kg/day), non-fibrous carbohydrates (0.858 kg/day), and metabolizable energy (5.66 Mcal/day). Also, the fiber sources did not influence dry matter and nutrient digestibility (P > 0.05). The association of cactus cladodes with silages, hay, and sugarcane bagasse did not change milk production, milk production corrected for 3.5% of fat and corrected for energy (2.78; 2.53 and 2,55 kg/day, respectively), in addition to milk composition (P > 0.05). No differences were observed in ingestive behavior (P > 0.05). Any fiber sources evaluated are recommended.

Cerebral Microbleeds in Fragile X-Associated Tremor/Ataxia Syndrome.

BACKGROUND: Fragile X-associated tremor/ataxia syndrome is a neurodegenerative disease of late onset developed by carriers of the premutation in the fragile x mental retardation 1 (FMR1) gene. Pathological features of neurodegeneration in fragile X-associated tremor/ataxia syndrome include toxic levels of FMR1 mRNA, ubiquitin-positive intranuclear inclusions, white matter disease, iron accumulation, and a proinflammatory state. OBJECTIVE: The objective of this study was to analyze the presence of cerebral microbleeds in the brains of patients with fragile X-associated tremor/ataxia syndrome and investigate plausible causes for cerebral microbleeds in fragile X-associated tremor/ataxia syndrome. METHODS: We collected cerebral and cerebellar tissue from 15 fragile X-associated tremor/ataxia syndrome cases and 15 control cases carrying FMR1 normal alleles. We performed hematoxylin and eosin, Perls and Congo red stains, ubiquitin, and amyloid ß protein immunostaining. We quantified the number of cerebral microbleeds, amount of iron, presence of amyloid ß within the capillaries, and number of endothelial cells containing intranuclear inclusions. We evaluated the relationships between pathological findings using correlation analysis. RESULTS: We found intranuclear inclusions in the endothelial cells of capillaries and an increased number of cerebral microbleeds in the brains of those with fragile X-associated tremor/ataxia syndrome, both of which are indicators of cerebrovascular dysfunction. We also found a suggestive association between the amount of capillaries that contain amyloid ß in the cerebral cortex and the rate of disease progression. CONCLUSION: We propose microangiopathy as a pathologic feature of fragile X-associated tremor/ataxia syndrome. © 2021 International Parkinson and Movement Disorder Society.

Inequities in diagnosis of Fragile X syndrome in Colombia.

BACKGROUND: Fragile X syndrome (FXS) is the most common cause of inherited intellectual disability and autism spectrum disorder (ASD). In Colombia, there are no screening or testing protocols established for the diagnosis of FXS. In this study, we aimed to describe the diagnostic trends of FXS in Colombia. METHODS: Data were included on 1322 individuals obtained based on data from the only 2 databases available. Sociodemographic information and data related to the diagnostic process were obtained and included in this study. RESULTS: The average age at the time of diagnosis for individuals with the full mutation (FM) was of 26.9 ± 2.57 years and was strongly dependent on sex and socioeconomic status. Most individuals with a molecular diagnosis were from the main cities. CONCLUSION: The overall age of diagnosis of FXS is later in life than reports from other countries. Restricted access to molecular testing through the national health system might explain this discrepancy in Colombia.

Correction: Modelled health benefits of a sugar-sweetened beverage tax across different socioeconomic groups in Australia: A cost-effectiveness and equity analysis.

[This corrects the article DOI: 10.1371/journal.pmed.1002326.].

Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): Pathophysiology and Clinical Implications.

The fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder seen in older premutation (55-200 CGG repeats) carriers of FMR1. The premutation has excessive levels of FMR1 mRNA that lead to toxicity and mitochondrial dysfunction. The clinical features usually begin in the 60 s with an action or intention tremor followed by cerebellar ataxia, although 20% have only ataxia. MRI features include brain atrophy and white matter disease, especially in the middle cerebellar peduncles, periventricular areas, and splenium of the corpus callosum. Neurocognitive problems include memory and executive function deficits, although 50% of males can develop dementia. Females can be less affected by FXTAS because of a second X chromosome that does not carry the premutation. Approximately 40% of males and 16% of female carriers develop FXTAS. Since the premutation can occur in less than 1 in 200 women and 1 in 400 men, the FXTAS diagnosis should be considered in patients that present with tremor, ataxia, parkinsonian symptoms, neuropathy, and psychiatric problems. If a family history of a fragile X mutation is known, then FMR1 DNA testing is essential in patients with these symptoms.

Cost-effectiveness of community-based childhood obesity prevention interventions in Australia.

OBJECTIVES: The objective of this study is to examine, from a limited societal perspective, the cost-effectiveness of community-based obesity prevention interventions (CBIs)-defined as a programme of community-level strategies to promote healthy eating and physical activity for Australian children (aged 5-18 years). METHODS: The effectiveness of CBIs was determined by undertaking a literature review and meta-analysis. Commonly implemented strategies to increase physical activity and improve nutrition were costed (in 2010 Australian dollars) to determine the average cost of a generic programme. A multiple cohort Markov model that simulates diseases associated with overweight and obesity was used to estimate the health benefits, measured as health-adjusted life years (HALYs) and healthcare-related cost offsets from diseases averted due to exposure to the intervention. Health and cost outcomes were estimated over the lifetime of the target population. Monte-Carlo simulation was used to assess second-order uncertainty of input parameters to estimate mean incremental cost-effectiveness ratios (ICER) with 95% uncertainty intervals (UIs). Scenario analyses tested variations in programme intensity, target population, and duration of effect. RESULTS: The meta-analysis revealed a small but significant difference in BMI z-score (mean difference of - 0.07 (95% UI: - 0.13 to - 0.01)) favouring the CBI community compared with the control. The estimated net cost of implementing CBIs across all local government areas (LGAs) in Australia was AUD426M (95% UI: AUD3M to AUD823M) over 3 years. This resulted in 51,792 HALYs gained (95% UI: 6816 to 96,972) over the lifetime of the cohort. The mean ICER was AUD8155 per HALY gained (95% UI: AUD237 to AUD81,021), with a 95% probability of being cost-effective at a willingness to pay threshold of AUD50,000 per HALY. CONCLUSIONS: CBIs are cost-effective obesity prevention initiatives; however, implementation across Australia will be (relatively) expensive when compared with current investments in preventive health.

Question 1: Why do children still die from asthma?

Asthma is one of the commonest chronic conditions in children and can occasionally be fatal. Little has changed regarding the risk factors for children dying from asthma in the last 30 years. The majority of deaths from asthma occur in children from socio-economically disadvantaged backgrounds. These should be preventable with better education of families, oversight of medication adherence and improved communication between health care professionals and families. More needs to be done to deliver basic messages more effectively about asthma management to the most vulnerable in communities around the world.

Modelled health benefits of a sugar-sweetened beverage tax across different socioeconomic groups in Australia: A cost-effectiveness and equity analysis.

BACKGROUND: A sugar-sweetened beverage (SSB) tax in Mexico has been effective in reducing consumption of SSBs, with larger decreases for low-income households. The health and financial effects across socioeconomic groups are important considerations for policy-makers. From a societal perspective, we assessed the potential cost-effectiveness, health gains, and financial impacts by socioeconomic position (SEP) of a 20% SSB tax for Australia. METHODS AND FINDINGS: Australia-specific price elasticities were used to predict decreases in SSB consumption for each Socio-Economic Indexes for Areas (SEIFA) quintile. Changes in body mass index (BMI) were based on SSB consumption, BMI from the Australian Health Survey 2011-12, and energy balance equations. Markov cohort models were used to estimate the health impact for the Australian population, taking into account obesity-related diseases. Health-adjusted life years (HALYs) gained, healthcare costs saved, and out-of-pocket costs were estimated for each SEIFA quintile. Loss of economic welfare was calculated as the amount of deadweight loss in excess of taxation revenue. A 20% SSB tax would lead to HALY gains of 175,300 (95% CI: 68,700; 277,800) and healthcare cost savings of AU$1,733 million (m) (95% CI: $650m; $2,744m) over the lifetime of the population, with 49.5% of the total health gains accruing to the 2 lowest quintiles. We estimated the increase in annual expenditure on SSBs to be AU$35.40/capita (0.54% of expenditure on food and non-alcoholic drinks) in the lowest SEIFA quintile, a difference of AU$3.80/capita (0.32%) compared to the highest quintile. Annual tax revenue was estimated at AU$642.9m (95% CI: $348.2m; $1,117.2m). The main limitations of this study, as with all simulation models, is that the results represent only the best estimate of a potential effect in the absence of stronger direct evidence. CONCLUSIONS: This study demonstrates that from a 20% tax on SSBs, the most HALYs gained and healthcare costs saved would accrue to the most disadvantaged quintiles in Australia. Whilst those in more disadvantaged areas would pay more SSB tax, the difference between areas is small. The equity of the tax could be further improved if the tax revenue were used to fund initiatives benefiting those with greater disadvantage.

[Pediatric asthma hospitalization in Chile: 2001-2014]. / Hospitalizaciones por asma infantil en Chile: 2001-2014.

Bronchial asthma is the most prevalent chronic disease in children. Every year an important number of asthmatic children is hospitalized for asthma crisis. The magnitude of this problem in Chile is unknown. OBJECTIVE: To evaluated the asthma hospitalization rate in 5-15 year-old children and evaluate their evolution. PATIENTS AND METHOD: We calculate the asthma hospitalization rate in children based on data from the National Hospitalization Discharge Registry from the Statistics and Health Information Department of the Ministry of Health (DEIS) and the National Institute of Statistics (INE). We evaluate the evolution of these rates from 2001 to 2014. RESULTS: We observed a significant increase in the asthma hospitalization rates in children from 3,8 for 10.000 inhabitants in 2001 to 7,8 for 10.000 inhabitants in 2014. The average age was 8,5 years ± 2,7. Male gender was predominant (57,58%) with a mean length of stay of 3 days (range 1-12). CONCLUSIONS: The actual asthma hospitalization rate in Chile is 7,8 for 10.000 inhabitants for children 5 to 15 years old, with a double increase in this rate during the 14 year period analyzed.

Nausea and Vomiting as Initial Manifestations of Pediatric NMOSD.

Intractable nausea and vomiting are commonly attributed to gastrointestinal (GI) conditions but can sometimes be a symptom of an underlying central nervous system disease. One potentially overlooked neurologic cause of intractable nausea and vomiting that is refractory to antiemetics is area postrema syndrome (APS). APS is a condition characterized by lesions of the dorsal caudal medulla and is considered a core clinical feature of neuromyelitis optica spectrum disorder (NMOSD). APS is present in up to 30% of patients ultimately diagnosed with NMOSD and can be the first presenting symptom of NMOSD in 12% of patients, as our case illustrates. Importantly, APS is highly responsive to immunotherapy. We present the case of a 14-year-old female with a history of migraines who presented to the emergency department multiple times for persistent nausea, vomiting, and hiccups. Multiple GI diagnoses were considered until she developed additional neurologic symptoms that prompted further workup and revealed the final diagnosis of NMOSD-APS. We posit that NMOSD-APS should be considered in the differential diagnosis for patients with intractable nausea and vomiting, especially in patients with a negative GI workup result and poor response to antiemetics.

Timely delivery of PORT for head and neck squamous cell carcinoma in a county hospital.

Objectives: The objective of this study was to compare the rate of post-operative radiation therapy (PORT) initiation within 6 weeks for head and neck squamous cell carcinoma patients treated at a safety net, academic institutio between 2019 and 2021 versus those treated in 2022 after implementation of a new clinical pathway. Methods: A retrospective case-control study was performed at a single tertiary care, safety-net, academic institution. Patient demographics, tumor characteristics, dates of surgery, and other treatment dates were collected from the electronic medical record. The time from surgery to PORT was calculated. Patients who started radiation treatment within 42 days of surgery were regarded as having started PORT on time. The demographics, tumor characteristics, and rate of timely PORT for the two cohorts of patients were compared. Results: From 2018 to 2021, our rate of PORT initiation within 6 weeks of surgery was 12% (n = 57). In 2022, our rate of timely PORT was 88% (n = 16), p < 0.5. Patient demographics and characteristics were similar with the exception of marital status and use of free-flap reconstruction. The 2022 cohort was more likely to be single (p < 0.5), and all patients underwent free-flap reconstruction in 2022 (p < 0.05). Conclusion: Early referrals, frequent communication, and use of a secure registry were the key to the success found by our group despite the socioeconomic challenges of our underserved, safety-net hospital patient population. The changes made at our institution should serve as a template for other institutions seeking to improve the quality of care for their HNSCC patients.

Comparing Mediators and Moderators of Mental Health Outcomes from the Implementation of Group Problem Management Plus (PM+) among Venezuelan Refugees and Migrants and Colombian Returnees in Northern Colombia.

Colombia hosts the largest number of refugees and migrants fleeing the humanitarian emergency in Venezuela, many of whom experience high levels of displacement-related trauma and adversity. Yet, Colombian mental health services do not meet the needs of this population. Scalable, task-sharing interventions, such as Group Problem Management Plus (Group PM+), have the potential to bridge this gap by utilizing lay workers to provide the intervention. However, the current literature lacks a comprehensive understanding of how and for whom Group PM+ is most effective. This mixed methods study utilized data from a randomized effectiveness-implementation trial to examine the mediators and moderators of Group PM+ on mental health outcomes. One hundred twenty-eight migrant and refugee women in northern Colombia participated in Group PM+ delivered by trained community members. Patterns in moderation effects showed that participants in more stable, less marginalized positions improved the most. Results from linear regression models showed that Group PM+-related skill acquisition was not a significant mediator of the association between session attendance and mental health outcomes. Participants and facilitators reported additional possible mediators and community-level moderators that warrant future research. Further studies are needed to examine mediators and moderators contributing to the effectiveness of task-shared, scalable, psychological interventions in diverse contexts.

Effect of the Deposit Temperature of ZnO Doped with Ni by HFCVD.

The effect of the deposit temperature of zinc oxide (ZnO) doped with nickel (Ni) by hot filament chemical vapor deposition (HFCVD) technique is reported in this work. The technique allows depositing ZnO:Ni in short intervals (1 min). A deposit of undoped ZnO is used as a reference sample. The reference sample was deposited at 500 °C. The ZnO:Ni samples were deposited at 500 °C, 400 °C, 350 °C, and 300 °C. The samples were studied using structural, morphological, and optical characterization techniques. The Ni incorporation to the ZnO lattice was verified by the shift of the X-ray diffraction peaks, the Raman peaks, the band gap, and the photoluminescence measurements. It was found that the deposit temperature affects the structural, morphological, and optical properties of the ZnO:Ni samples too. The structure of the ZnO:Ni samples corresponds to the hexagonal structure. Different microstructures shapes such as spheres, sea urchins, and agglomerate were found in samples; their change is attributed to the deposit temperature variation. The intensity of the photoluminescence of the ZnO:Ni improves concerning the ZnO due to the Ni incorporation, but it decreases as the deposit temperature decreases.

Quality of life related to both general and oral health two years after treatment for subcondylar fracture.

The success of treatment for condylar fractures is usually assessed by functional outcomes, while studies on patient perceptions are scarce. A cross-sectional study was performed to assess the middle-term quality of life, related to both general health and oral health, of patients treated for subcondylar fracture, either by open reduction or by closed fixation, compared to healthy volunteers. In a single trauma centre, among 226 consecutive patients with subcondylar fractures that were treated in years 2018-2019 (two to three years prior to the survey), 148 fulfilled the selection criteria. They were classified as those with other facial fractures that were treated by open reduction (n = 79), and those without other fractures that were treated either by open reduction (n = 34) or by closed fixation (n = 35). An age matched group of healthy volunteers (n = 65) also participated in the study. All participants replied to the Short-Form-Health-Survey (SF-36) and the Oral-Health-Impact-Profile (OHIP-49), using the social messenger platform WhatsApp. The SF-36 showed that patients with closed-fixation reported better mental health than patients with open reduction, but worse than healthy volunteers. Contrariwise, on the OHIP-49, compared to patients with open reduction (with/without other facial fractures) and to healthy volunteers, patients with closed-fixation reported worse quality of life on physical pain, psychological discomfort, and physical disability. The influence of age was evident just on the OHIP-49, on the report of physical limitation and physical pain. Two to three years after the subcondylar fracture, patients treated either by open reduction or closed fixation might report decreased quality of life compared to healthy volunteers; patients treated by open reduction might report lesser mental health related quality of life (SF-36), but superior oral health related quality of life (OHIP-49) than patients treated by closed fixation.

Severe Vaginal Myiasis: Successful Management With Ivermectin.

Myiasis refers to infestation of living animals or humans by maggots or fly larvae. Urogenital myiasis is a rare condition that is linked to poor sanitary conditions and limited access to healthcare and with few published case reports. Here, we describe the case of a 67-year-old homeless woman with multiple comorbidities, who presented with extensive vaginal myiasis requiring inpatient management with ivermectin, ceftriaxone, and metronidazole and daily larvae extraction and debridement. The relevance of this case is providing a report of a successful management with ivermectin of a case of severe vaginal myiasis. Severe cases of vaginal myiasis can require repeated debridement of necrotic tissue and systemic antibiotics in addition to antiparasitic medication. People living under poor sanitary conditions and with poor hygienic practices are at increased risk for severe vaginal myiasis.

AMAZONIA CAMTRAP: A data set of mammal, bird, and reptile species recorded with camera traps in the Amazon forest.

The Amazon forest has the highest biodiversity on Earth. However, information on Amazonian vertebrate diversity is still deficient and scattered across the published, peer-reviewed, and gray literature and in unpublished raw data. Camera traps are an effective non-invasive method of surveying vertebrates, applicable to different scales of time and space. In this study, we organized and standardized camera trap records from different Amazon regions to compile the most extensive data set of inventories of mammal, bird, and reptile species ever assembled for the area. The complete data set comprises 154,123 records of 317 species (185 birds, 119 mammals, and 13 reptiles) gathered from surveys from the Amazonian portion of eight countries (Brazil, Bolivia, Colombia, Ecuador, French Guiana, Peru, Suriname, and Venezuela). The most frequently recorded species per taxa were: mammals: Cuniculus paca (11,907 records); birds: Pauxi tuberosa (3713 records); and reptiles: Tupinambis teguixin (716 records). The information detailed in this data paper opens up opportunities for new ecological studies at different spatial and temporal scales, allowing for a more accurate evaluation of the effects of habitat loss, fragmentation, climate change, and other human-mediated defaunation processes in one of the most important and threatened tropical environments in the world. The data set is not copyright restricted; please cite this data paper when using its data in publications and we also request that researchers and educators inform us of how they are using these data.

Overlapping Molecular Pathways Leading to Autism Spectrum Disorders, Fragile X Syndrome, and Targeted Treatments.

Autism spectrum disorders (ASD) are subdivided into idiopathic (unknown) etiology and secondary, based on known etiology. There are hundreds of causes of ASD and most of them are genetic in origin or related to the interplay of genetic etiology and environmental toxicology. Approximately 30 to 50% of the etiologies can be identified when using a combination of available genetic testing. Many of these gene mutations are either core components of the Wnt signaling pathway or their modulators. The full mutation of the fragile X mental retardation 1 (FMR1) gene leads to fragile X syndrome (FXS), the most common cause of monogenic origin of ASD, accounting for ~ 2% of the cases. There is an overlap of molecular mechanisms in those with idiopathic ASD and those with FXS, an interaction between various signaling pathways is suggested during the development of the autistic brain. This review summarizes the cross talk between neurobiological pathways found in ASD and FXS. These signaling pathways are currently under evaluation to target specific treatments in search of the reversal of the molecular abnormalities found in both idiopathic ASD and FXS.