Co-infection of Helicobacter Pylori and intestinal parasites in children of selected Low-income communities in Lagos State, Nigeria.

Helicobacter pylori and intestinal parasites cause gastrointestinal diseases with a high prevalence in children in resource limited developing countries. There is paucity of information in Nigeria on co-infection of H. pylori and intestinal parasites. The study was conducted to determine the prevalence of H. pylori and parasite co-infection in children from selected low-income communities in Lagos, Nigeria. Fecal samples were collected from 151 healthy children aged ≤11 years across six low-income communities in Lagos. H. pylori was detected using stool antigen test and conventional PCR assay, intestinal parasites were detected using formol-ether concentration and nested PCR assay. Structured questionnaires were administered to parents and legal guardians of the children by an interviewer to collect relevant data on demographic and lifestyle factors. The prevalence of H. pylori was 31.79% (48), with a higher prevalence in children aged 2-3 years. The prevalence of intestinal parasites was 21.19% (32) with the lowest frequency found in children aged 8-9 years. The parasites detected include: A. lumbricoides (10.6%), G. intestinalis (7.3%), hookworm (1.99%), E. histolytica (0.66%), S. mansoni (0.66%). There was co-infection prevalence of 10.6% (16) which was associated with the parasites: G. intestinalis (7.3%) and A. lumbricoides (3.97%). Polyparasitism with G. intestinalis and A. lumbricoides was reported in 2 children infected with H. pylori. This study which is the first reported in Lagos established a low prevalence of H. pylori and intestinal parasite co-infection in children and provides better understanding of the epidemiology of H. pylori infection associated with intestinal parasites in Nigeria.

Small skeletons show size-specific scaling: an exploration of allometry in the mammalian lumbar spine.

Studies of vertebrate bone biomechanics often focus on skeletal adaptations at upper extremes of body mass, disregarding the importance of skeletal adaptations at lower extremes. Yet mammals are ancestrally small and most modern species have masses under 5 kg, so the evolution of morphology and function at small size should be prioritized for understanding how mammals subsist. We examined allometric scaling of lumbar vertebrae in the small-bodied Philippine endemic rodents known as cloud rats, which vary in mass across two orders of magnitude (15.5 g-2700 g). External vertebral dimensions scale with isometry or positive allometry, likely relating to body size and nuances in quadrupedal posture. In contrast to most mammalian trabecular bone studies, bone volume fraction and trabecular thickness scale with positive allometry and isometry, respectively. It is physiologically impossible for these trends to continue to the upper extremes of mammalian body size, and we demonstrate a fundamental difference in trabecular bone allometry between large- and small-bodied mammals. These findings have important implications for the biomechanical capabilities of mammalian bone at small body size; for the selective pressures that govern skeletal evolution in small mammals; and for the way we define 'small' and 'large' in the context of vertebrate skeletons.

Daytime dexmedetomidine sedation with closed-loop acoustic stimulation alters slow wave sleep homeostasis in healthy adults.

Background: The alpha-2 adrenergic agonist dexmedetomidine induces EEG patterns resembling those of non-rapid eye movement (NREM) sleep. Fulfilment of slow wave sleep (SWS) homeostatic needs would address the assumption that dexmedetomidine induces functional biomimetic sleep states. Methods: In-home sleep EEG recordings were obtained from 13 healthy participants before and after dexmedetomidine sedation. Dexmedetomidine target-controlled infusions and closed-loop acoustic stimulation were implemented to induce and enhance EEG slow waves, respectively. EEG recordings during sedation and sleep were staged using modified American Academy of Sleep Medicine criteria. Slow wave activity (EEG power from 0.5 to 4 Hz) was computed for NREM stage 2 (N2) and NREM stage 3 (N3/SWS) epochs, with the aggregate partitioned into quintiles by time. The first slow wave activity quintile served as a surrogate for slow wave pressure, and the difference between the first and fifth quintiles as a measure of slow wave pressure dissipation. Results: Compared with pre-sedation sleep, post-sedation sleep showed reduced N3 duration (mean difference of -17.1 min, 95% confidence interval -30.0 to -8.2, P=0.015). Dissipation of slow wave pressure was reduced (P=0.02). Changes in combined durations of N2 and N3 between pre- and post-sedation sleep correlated with total dexmedetomidine dose, (r=-0.61, P=0.03). Conclusions: Daytime dexmedetomidine sedation and closed-loop acoustic stimulation targeting EEG slow waves reduced N3/SWS duration and measures of slow wave pressure dissipation on the post-sedation night in healthy young adults. Thus, the paired intervention induces sleep-like states that fulfil certain homeostatic NREM sleep needs in healthy young adults. Clinical trial registration: ClinicalTrials.gov NCT04206059.

Nuclear Magnetic Resonance Chemical Shift as a Probe for Single-Molecule Charge Transport.

Existing modelling tools, developed to aid the design of efficient molecular wires and to better understand their charge-transport behaviour and mechanism, have limitations in accuracy and computational cost. Further research is required to develop faster and more precise methods that can yield information on how charge transport properties are impacted by changes in the chemical structure of a molecular wire. In this study, we report a clear semilogarithmic correlation between charge transport efficiency and nuclear magnetic resonance chemical shifts in multiple series of molecular wires, also accounting for the presence of chemical substituents. The NMR data was used to inform a simple tight-binding model that accurately captures the experimental single-molecule conductance values, especially useful in this case as more sophisticated density functional theory calculations fail due to inherent limitations. Our study demonstrates the potential of NMR spectroscopy as a valuable tool for characterising, rationalising, and gaining additional insights on the charge transport properties of single-molecule junctions.

Mepolizumab improves sense of smell in severe chronic rhinosinusitis with nasal polyps: SYNAPSE.

BACKGROUND: Loss of smell is one of the most bothersome and difficult-to-treat symptoms in patients with severe chronic rhinosinusitis with nasal polyps (CRSwNP). METHODOLOGY: SYNAPSE was a 52-week Phase III study of 4-weekly mepolizumab (100 mg subcutaneously) plus standard of care in adults with severe bilateral CRSwNP. This post hoc analysis assessed changes from baseline to study end in loss of smell visual analogue scale (VAS) symptom score, in patients stratified by several baseline clinical characteristics. SinoNasal Outcomes Test (SNOT)-22 sense of smell/taste item and University of Pennsylvania Smell Identification Test (UPSIT) scores were also assessed. RESULTS: SYNAPSE enrolled 407 patients (mepolizumab=206; placebo=201) with impaired sense of smell at baseline. Improvements from baseline to study end in loss of smell VAS score were greater with mepolizumab versus placebo (treatment difference: −0.37) and most notable in patients with fewer or more recent prior surgeries (treatment difference: 1 vs 2 vs more than 2 prior surgeries,−1.29 vs −0.23 vs −0.07; =3 years since last surgery, −0.89 vs 0.22). Approximately 25% of patients had baseline UPSIT scoresavailable; among those scoring =19 by study end. The SNOT-22 sense of smell/taste item score improved with mepolizumab versus placebo. CONCLUSIONS: Mepolizumab treatment improved patients' perceived sense of smell, as measured by loss of smell VAS score and SNOT-22 sense of smell/taste item score in patients with severe refractory CRSwNP.

The Adaptive, Pain Sensitive, and Global Symptoms Clusters: Evidence from a Patient-Based Study.

OBJECTIVES: The largest epidemiologic study conducted about painful temporomandibular disorders (pTMDs) to date identified 3 clusters of individuals with similar symptoms-adaptive, pain sensitive, and global symptoms-which hold promise as a means of personalizing pain care. Our goal was to compare the clinical and psychological characteristics that are consistent with a pTMD clinical examination among patients who are seeking care and assigned to the different clusters. METHODS: This cross-sectional study used data from the medical records of patients attending Duke Innovative Pain Therapies between August 2017 and April 2021 who received a pTMD diagnosis (i.e., myalgia) and consented to have their data used for research. Data included orofacial and pain-related measures, dental features, and psychological measures. We used the Rapid OPPERA Algorithm to assign clusters to patients and multinomial regression to determine the likelihood (odds ratios [OR] and 95% confidence intervals [CI]) of being assigned to the pain sensitive or global symptoms cluster attributed to each measure. RESULTS: In total, 131 patients were included in this study and assigned a cluster: adaptive (n = 54, 41.2%), pain sensitive (n = 49, 37.4%), and global symptoms (n = 28, 21.4%). The PS cluster displayed greater numbers of temporomandibular joint sites (OR, 1.29; 95% CI, 1.01 to 1.65) and masticatory (1.48; 1.19 to 1.83) and cervical (1.23; 1.09 to 1.39) muscles with pain evoked by palpation. The GS cluster displayed greater scores of pain catastrophizing (1.04; 1.01 to 1.06) and perceived stress (1.23; 1.03 to 1.46) and was more likely to report persistent pain (16.23; 1.92 to 137.1) of higher impact (1.43; 1.14 to 1.80). CONCLUSION: Our findings support that care-seeking patients with pTMDs who are assigned to the GS cluster display a poorer psychological profile, even though those assigned to the PS cluster display more measures consistent with orofacial pain. Findings also establish the PS cluster as a group that does not display psychological comorbidities despite being hypersensitive. KNOWLEDGE TRANSFER STATEMENT: This study informs clinicians that patients seeking care for painful temporomandibular disorders, in specific cases of myalgia, can be classified into 1 of 3 groups that display unique profiles of symptoms. Most importantly, it emphasizes the importance of examining patients with painful temporomandibular disorders in a holistic manner that includes assessing symptoms of psychological distress. Patients with greater psychological distress will likely benefit from multidisciplinary treatment strategies that may include psychological treatments.

Do contaminants compromise the use of recycled nutrients in organic agriculture? A review and synthesis of current knowledge on contaminant concentrations, fate in the environment and risk assessment.

Use of nutrients recycled from societal waste streams in agriculture is part of the circular economy, and in line with organic farming principles. Nevertheless, diverse contaminants in waste streams create doubts among organic farmers about potential risks for soil health. Here, we gather the current knowledge on contaminant levels in waste streams and recycled nutrient sources, and discuss associated risks. For potentially toxic elements (PTEs), the input of zinc (Zn) and copper (Cu) from mineral feed supplements remains of concern, while concentrations of PTEs in many waste streams have decreased substantially in Europe. The same applies to organic contaminants, although new chemical groups such as flame retardants are of emerging concern and globally contamination levels differ strongly. Compared to inorganic fertilizers, application of organic fertilizers derived from human or animal feces is associated with an increased risk for environmental dissemination of antibiotic resistance. The risk depends on the quality of the organic fertilizers, which varies between geographical regions, but farmland application of sewage sludge appears to be a safe practice as shown by some studies (e.g. from Sweden). Microplastic concentrations in agricultural soils show a wide spread and our understanding of its toxicity is limited, hampering a sound risk assessment. Methods for assessing public health risks for organic contaminants must include emerging contaminants and potential interactions of multiple compounds. Evidence from long-term field experiments suggests that soils may be more resilient and capable to degrade or stabilize pollutants than often assumed. In view of the need to source nutrients for expanding areas under organic farming, we discuss inputs originating from conventional farms vs. non-agricultural (i.e. societal) inputs. Closing nutrient cycles between agriculture and society is feasible in many cases, without being compromised by contaminants, and should be enhanced, aided by improved source control, waste treatment and sound risk assessments.

Patterns of evolution in MHC class II DQA and DQB exon 2 genes of Alpine mountain hares, Lepus timidus varronis, and sympatric and parapatric brown hares, L. europaeus, from Switzerland.

In natural populations, hybridization is known to occur between a wide range of species. However, its evolutionary significance is less clear. Genes involved in fighting pathogens are considered excellent candidates for studying adaptive introgression, although both introgression and balancing selection can generate similar patterns of diversity and differentiation. Here, we compared DQA and DQB MHC class II and microsatellite allelic diversity of sympatric and parapatric mountain (Lepus timidus) and brown hare (L. europaeus) populations from Switzerland. We detected higher genetic diversity in brown hares compared to mountain hares at both MHC and microsatellite loci. We consider the observed patterns of microsatellite diversity both for L. europaeus and L. timidus as result of stochastic demographic processes while the pattern of MHC polymorphism of the studied hare populations can be explained by pathogen-driven selection. Rare bidirectional gene flow between both hare species seems to occur specifically for MHC alleles. However, the high number of shared alleles showing similar high frequency in both species suggests that reciprocally exchanged MHC alleles are being maintained via balancing selection. Adaptation to similar pathogen communities can also lead to parallel selection of MHC alleles. Positive selection, recombination and mutations have played different roles in shaping the patterns of MHC allelic diversity in and differentiation between both species. Results for the latter evolutionary forces do not show a better matching between the sympatric populations compared to the parapatric ones, suggesting a minor role of introgression for the observed evolutionary patterns of the studied hare species.

Multi-Domain Interventions for Dementia Prevention - A Systematic Review.

OBJECTIVES: There is a growing incidence of cognitive decline and dementia associated with the ageing population. Lifestyle factors such as diet, physical activity, and cognitive activities may individually or collectively be undertaken to increase one's odds of preventing cognitive decline and future dementia. This study will examine whether clinical trials using multidomain lifestyle intervention can significantly decrease the risk of cognitive decline and therefore dementia. DESIGN, SETTING AND PARTICIPANTS: This systematic literature review of multidomain lifestyle interventions for the prevention of cognitive decline and dementia followed the PRISMA guidelines. Clinical trials involving multidomain intervention (i.e., diet and physical activity, or without cognitive training) in older adults (≥ 49 years old) at higher risk of dementia were identified through 5 electronic databases (EMBASE, MEDLINE, CINAHL, Cochrane, and Scopus). A comprehensive search was performed to identify and retrieve publications until 15 November 2022. Trials were published in English. RESULTS: The included studies (n=15) assessed change in cognition in response to a multidomain lifestyle intervention. However, the cognitive outcome measures used in these studies were heterogeneous. Despite this heterogeneity, two thirds of the studies showed improvement in cognition following a multidomain intervention (n=10 with a total of 9,439 participants). However, five studies reported no improvement in cognition following the multidomain intervention. The most common form of dietary intervention included higher amount of fruit and vegetable intake; whole-grain cereal products instead of refined; low fat options in milk and meat products; and limiting sucrose intake to less than 50 g/day. Most clinical trial studies were powered to examining the effects of multidomain interventions in cognition but were not designed to test the contribution of individual domains (i.e., dietary changes, increased physical activity, or increased cognitive stimulation alone). CONCLUSION: This systematic review aimed to determine the effect of multimodal lifestyle interventions on cognitive outcomes in older adults at risk of dementia. We found that participants with conditions that may increase the risk of dementia, (e.g., hypertension, cardiovascular fragility) do benefit from multi-modal lifestyle changes including diet, physical activity, and cognitive training. Two thirds of studies using multidomain lifestyle interventions showed improvements in cognitive function. Trials with a focus on cognitive training, dietary improvement, and physical activity may prevent or delay cognitive decline in older adults including those at risk of developing dementia. Future studies should consider longer follow-up periods and adequate power to be able to examine the effects of each lifestyle component in the context of multimodal interventions.

Comparative Effectiveness and Durability of Biologics in Clinical Practice: Month 12 Outcomes from the International, Observational Psoriasis Study of Health Outcomes (PSoHO).

INTRODUCTION: Given the chronic nature of psoriasis (PsO), more studies are needed that directly compare the effectiveness of different biologics over long observation periods. This study compares the effectiveness and durability through 12 months of anti-interleukin (IL)-17A biologics relative to other approved biologics in patients with moderate-to-severe psoriasis in a real-world setting. METHODS: The Psoriasis Study of Health Outcomes (PSoHO) is an ongoing 3-year, prospective, non-interventional cohort study of 1981 adults with chronic moderate-to-severe plaque psoriasis initiating or switching to a new biologic. The study compares the effectiveness of anti-IL-17A biologics with other approved biologics and provides pairwise comparisons of seven individual biologics versus ixekizumab. The primary outcome was defined as the proportion of patients who had at least a 90% improvement in Psoriasis Area and Severity Index score (PASI90) and/or a score of 0 or 1 in static Physician Global Assessment (sPGA). Secondary objective comparisons included the proportion of patients who achieved PASI90, PASI100, a Dermatology Life Quality Index (DLQI) score of 0 or 1, and three different actions of durability of treatment response. Unadjusted response rates are presented alongside the primary analysis, which uses frequentist model averaging (FMA) to evaluate the adjusted comparative effectiveness. RESULTS: Compared to the other biologics cohort, the anti-IL-17A cohort had a higher response rate (68.0% vs. 65.1%) and significantly higher odds of achieving the primary outcome at month 12. The two cohorts had similar response rates for PASI100 (40.5% and 37.1%) and PASI90 (53.9% and 51.7%) at month 12, with no significant differences between the cohorts in the adjusted analyses. At month 12, the response rates across the individual biologics were 53.5-72.6% for the primary outcome, 27.6-48.3% for PASI100, and 41.7-61.4% for PASI90. CONCLUSIONS: These results show the comparative effectiveness of biologics at 6 and 12 months in the real-world setting. TRIAL REGISTRATION: ClinicalTrials.gov identifier EUPAS24207.

Lessons learnt from the COVID-19 pandemic in selected countries to inform strengthening of public health systems: a qualitative study.

INTRODUCTION: The COVID-19 pandemic has prompted governments internationally to consider strengthening their public health systems. To support the work of Ireland's Public Health Reform Expert Advisory Group, the Health Information and Quality Authority, an independent governmental agency, was asked to describe the lessons learnt regarding the public health response to COVID-19 internationally and the applicability of this response for future pandemic preparedness. METHODS: Semi-structured interviews with key public health representatives from nine countries were conducted. Interviews were conducted in March and April 2022 remotely via Zoom and were recorded. Notes were taken by two researchers, and a thematic analysis undertaken. RESULTS: Lessons learnt from the COVID-19 pandemic related to three main themes: 1) setting policy; 2) delivering public health interventions; and 3) providing effective communication. Real-time surveillance, evidence synthesis, and cross-sectoral collaboration were reported as essential for policy setting; it was noted that having these functions established prior to the pandemic would lead to a more efficient implementation in a health emergency. Delivering public health interventions such as testing, contact tracing, and vaccination were key to limiting and or mitigating the spread of the SARS-CoV-2 virus. However, a number of challenges were highlighted such as staff capacity and burnout, delays in vaccination procurement, and reduced delivery of regular healthcare services. Clear, consistent, and regular communication of the scientific evidence was key to engaging citizens with mitigation strategies. However, these communication strategies had to compete with an infodemic of information being circulated, particularly through social media. CONCLUSIONS: Overall, functions relating to policy setting, public health interventions, and communication are key to pandemic response. Ideally, these should be established in the preparedness phase so that they can be rapidly scaled-up during a pandemic.

Current preconception care practice in the Netherlands - An evaluation study among birth care professionals.

OBJECTIVE: To evaluate the current practice of preconception care in the Netherlands and the perceptions of birth care professionals concerning preconception care. METHODS: We have developed a digital questionnaire and conducted a cross-sectional study by distributing the questionnaire among 102 organisations: 90 primary care midwifery practices and obstetric departments of 12 hospitals in the Southwest region of the Netherlands between December 2020 and March 2021. One birth care professional per organization was asked to complete the questionnaire. Descriptive statistics were used to present the results. FINDINGS: Respondents of eighty-three organisations (81.4 %) filled in the questionnaire, of whom 74 respondents were independent primary care midwives and 9 respondents were obstetricians. Preconception care mostly consisted of an individual consultation in which personalized health and lifestyle advice was given. Among the respondents, 44.4 % reported that the organization had a preconception care protocol. The way in which the consultation was carried out, as well as the health and lifestyle related questions asked, differed between respondents. More than 85 % of the respondents inquire about the following possible risk factors for complications: maternal illnesses, obstetric history, folic acid supplement intake, alcohol intake, smoking, substance abuse, hereditary disease, prescription medication, dietary habits, overweight, and birth defects in the family. The respondents acknowledged that preconception care should be offered to all couples who wish to become pregnant, as opposed to offering preconception care only to those with an increased risk of complications. Still, respondents do not receive many questions regarding the preconception period or requests for preconception care consultations. KEY CONCLUSION: Birth care professionals acknowledge the need for preconception care for all couples. In the Netherlands, preconception care consists mostly of an individual consultation with recommendations for health and lifestyle advice. However, the identification of risk factors varies between birth care professionals and less than half of the respondents indicate that they have a protocol available in their practice. Furthermore, the demand of parents-to-be for preconception care is low. More research, that includes more obstetricians, is necessary to investigate if there is a difference between the care provided by primary care midwives and obstetricians. IMPLICATIONS FOR PRACTICE: To increase the awareness and uptake of preconception care, it would be prudent to emphasize its importance to parents-to-be and professionals, and actively promote the use of widespread, standardized protocols for birth care professionals.

Altered motility in response to iron-limitation is regulated by lpdA in uropathogenic E. coli CFT073.

More than half of all women will experience a urinary tract infection (UTI) in their lifetime with most cases caused by uropathogenic Escherichia coli (UPEC). Bacterial motility enhances UPEC pathogenicity, resulting in more severe disease outcomes including kidney infection. Surprisingly, the connection between motility and iron limitation is mostly unexplored, despite the lack of free iron available in the host. Therefore, we sought to explore the potential connection between iron restriction and regulation of motility in UPEC. We cultured E. coli CFT073, a prototypical UPEC strain, in media containing an iron chelator. Under iron limitation, CFT073 had elevated fliC (flagella) promoter activity, driving motility on the leading edge of the colony. Furthermore, this iron-specific response was repressed by the addition of exogenous iron. We confirmed increased flagella expression in CFT073 by measuring fliC transcript, FliC protein, and surface-expressed flagella under iron-limited conditions. To define the regulatory mechanism, we constructed single knockouts of eight master regulators. The iron-regulated response was lost in crp, arcA, and fis mutants. Thus, we focused on the five genes regulated by all three transcription factors. Of the five genes knocked out, the iron-regulated motility response was most strongly dysregulated in an lpdA mutant, which also resulted in significantly lowered fitness in the murine model of ascending UTI. Collectively, we demonstrated that iron-mediated motility in CFT073 is regulated by lpdA , which contributes to the understanding of how uropathogens differentially regulate motility mechanisms in the iron-restricted host. Importance: Urinary tract infections (UTIs) are ubiquitous and responsible for over five billion dollars in associated health care costs annually. Both iron acquisition and motility are highly studied virulence factors associated with uropathogenic E. coli (UPEC), the main causative agent of uncomplicated UTI. This work is innovative by providing mechanistic insight into the synergistic relationship between these two critical virulence properties. Here, we demonstrate that iron limitation has pleiotropic effects with consequences that extend beyond metabolism, and impact other virulence mechanisms. Indeed, targeting iron acquisition as a therapy may lead to an undesirable enhancement of UPEC pathogenesis through increased motility. It is vital to understand the full breadth of UPEC pathogenesis to adequately respond to this common infection, especially with the increase of antibiotic resistant pathogens.

Two-Year Prognostic Utility of Plasma p217+tau across the Alzheimer's Continuum.

BACKGROUND: Plasma p217+tau has shown high concordance with cerebrospinal fluid (CSF) and positron emission tomography (PET) measures of amyloid-ß (Aß) and tau in Alzheimer's Disease (AD). However, its association with longitudinal cognition and comparative performance to PET Aß and tau in predicting cognitive decline are unknown. OBJECTIVES: To evaluate whether p217+tau can predict the rate of cognitive decline observed over two-year average follow-up and compare this to prediction based on Aß (18F-NAV4694) and tau (18F-MK6240) PET. We also explored the sample size required to detect a 30% slowing in cognitive decline in a 2-year trial and selection test cost using p217+tau (pT+) as compared to PET Aß (A+) and tau (T+) with and without p217+tau pre-screening. DESIGN: A prospective observational cohort study. SETTING: Participants of the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) and Australian Dementia Network (ADNeT). PARTICIPANTS: 153 cognitively unimpaired (CU) and 50 cognitively impaired (CI) individuals. MEASUREMENTS: Baseline p217+tau Simoa® assay, 18F-MK6240 tau-PET and 18F-NAV4694 Aß-PET with neuropsychological follow-up (MMSE, CDR-SB, AIBL-PACC) over 2.4 ± 0.8 years. RESULTS: In CI, p217+tau was a significant predictor of change in MMSE (ß = -0.55, p < 0.001) and CDR-SB (ß =0.61, p < 0.001) with an effect size similar to Aß Centiloid (MMSE ß = -0.48, p = 0.002; CDR-SB ß = 0.43, p = 0.004) and meta-temporal (MetaT) tau SUVR (MMSE: ß = -0.62, p < 0.001; CDR-SB: ß = 0.65, p < 0.001). In CU, only MetaT tau SUVR was significantly associated with change in AIBL-PACC (ß = -0.22, p = 0.008). Screening pT+ CI participants into a trial could lead to 24% reduction in sample size compared to screening with PET for A+ and 6-13% compared to screening with PET for T+ (different regions). This would translate to an 81-83% biomarker test cost-saving assuming the p217+tau test cost one-fifth of a PET scan. In a trial requiring PET A+ or T+, p217+tau pre-screening followed by PET in those who were pT+ would cost more in the CI group, compared to 26-38% biomarker test cost-saving in the CU. CONCLUSIONS: Substantial cost reduction can be achieved using p217+tau alone to select participants with MCI or mild dementia for a clinical trial designed to slow cognitive decline over two years, compared to participant selection by PET. In pre-clinical AD trials, p217+tau provides significant cost-saving if used as a pre-screening measure for PET A+ or T+ but in MCI/mild dementia trials this may add to cost both in testing and in the increased number of participants needed for testing.

Methods used to assess sleep in children who attend community-based mental health programmes: A systematic review.

Sleep quality and sleep duration are important for children's physical and mental health. Mental health diagnoses and sleep disturbances may be interlinked. We sought to identify the methods used to assess sleep in paediatric community-based mental health programmes. A systematic review was conducted using an a priori protocol to ascertain the sleep assessment methods used in paediatric community-based mental health programmes. Children for this review were defined as any person under the age of 19. Cochrane Library, CINAHL, Web of Science, ProQuest, APA PsycInfo, and PubMed databases were searched from January 2021 to March 2022. Of the 320 records screened, 314 records were excluded. Six studies were included for analysis. A variety of validated and non-validated sleep instruments were used to measure sleep quality and a range of sleep disturbances in community health programmes for children. There were a limited number of studies associated with sleep assessment in paediatric community-based settings suggesting this is an area of research that may be understudied. Sleep questionnaires were predominately completed by parents or guardians. Further research is required to establish the most effective method for screening sleep behaviour in paediatric community mental health programmes to understand the impact of sleep in the recovery of children and adolescents with mental health disorders.

Assessing complexity and dynamics in epidemics: geographical barriers and facilitators of foot-and-mouth disease dissemination.

Introduction: Physical and non-physical processes that occur in nature may influence biological processes, such as dissemination of infectious diseases. However, such processes may be hard to detect when they are complex systems. Because complexity is a dynamic and non-linear interaction among numerous elements and structural levels in which specific effects are not necessarily linked to any one specific element, cause-effect connections are rarely or poorly observed. Methods: To test this hypothesis, the complex and dynamic properties of geo-biological data were explored with high-resolution epidemiological data collected in the 2001 Uruguayan foot-and-mouth disease (FMD) epizootic that mainly affected cattle. County-level data on cases, farm density, road density, river density, and the ratio of road (or river) length/county perimeter were analyzed with an open-ended procedure that identified geographical clustering in the first 11 epidemic weeks. Two questions were asked: (i) do geo-referenced epidemiologic data display complex properties? and (ii) can such properties facilitate or prevent disease dissemination? Results: Emergent patterns were detected when complex data structures were analyzed, which were not observed when variables were assessed individually. Complex properties-including data circularity-were demonstrated. The emergent patterns helped identify 11 counties as 'disseminators' or 'facilitators' (F) and 264 counties as 'barriers' (B) of epidemic spread. In the early epidemic phase, F and B counties differed in terms of road density and FMD case density. Focusing on non-biological, geographical data, a second analysis indicated that complex relationships may identify B-like counties even before epidemics occur. Discussion: Geographical barriers and/or promoters of disease dispersal may precede the introduction of emerging pathogens. If corroborated, the analysis of geo-referenced complexity may support anticipatory epidemiological policies.

HIV, asymptomatic STI, and the rectal mucosal immune environment among young men who have sex with men.

Young men who have sex with men (YMSM) are disproportionately affected by HIV and bacterial sexually transmitted infections (STI) including gonorrhea, chlamydia, and syphilis; yet research into the immunologic effects of these infections is typically pursued in siloes. Here, we employed a syndemic approach to understand potential interactions of these infections on the rectal mucosal immune environment among YMSM. We enrolled YMSM aged 18-29 years with and without HIV and/or asymptomatic bacterial STI and collected blood, rectal secretions, and rectal tissue biopsies. YMSM with HIV were on suppressive antiretroviral therapy (ART) with preserved blood CD4 cell counts. We defined 7 innate and 19 adaptive immune cell subsets by flow cytometry, the rectal mucosal transcriptome by RNAseq, and the rectal mucosal microbiome by 16S rRNA sequencing and examined the effects of HIV and STI and their interactions. We measured tissue HIV RNA viral loads among YMSM with HIV and HIV replication in rectal explant challenge experiments among YMSM without HIV. HIV, but not asymptomatic STI, was associated with profound alterations in the cellular composition of the rectal mucosa. We did not detect a difference in the microbiome composition associated with HIV, but asymptomatic bacterial STI was associated with a higher probability of presence of potentially pathogenic taxa. When examining the rectal mucosal transcriptome, there was evidence of statistical interaction; asymptomatic bacterial STI was associated with upregulation of numerous inflammatory genes and enrichment for immune response pathways among YMSM with HIV, but not YMSM without HIV. Asymptomatic bacterial STI was not associated with differences in tissue HIV RNA viral loads or in HIV replication in explant challenge experiments. Our results suggest that asymptomatic bacterial STI may contribute to inflammation particularly among YMSM with HIV, and that future research should examine potential harms and interventions to reduce the health impact of these syndemic infections.

Psychedelics: Threshold of a Therapeutic Revolution.

This Special Issue of Neuropharmacology on psychedelics provides a timely and comprehensive update on progress following the previous Neuropharmacology Special Issue "Psychedelics: New Doors, Altered Perceptions". Remarkable advances have been made in basic and clinical research on psychedelics in the five years since 2018. It is partly based on the seminar series focused on psilocybin organized by the National Institutes of Health (NIH), USA from April to June 2021, the "NIH Psilocybin Research Speaker Series". Participants were world leading experts, including scientists, medical practitioners, clinical psychologists and oncologists, and attendees from additional disciplines of patient advocacy, law, government science policy and regulatory policy. To provide a global perspective, their contributions are complemented with reviews by some of the world's most eminent scientists in the field. The US Food and Drug Administration (FDA) has granted two breakthrough therapy designations for psilocybin in treatment resistant depression (TRD) in 2018 and major depressive disorder (MDD) in 2019, as well as for MDMA for the treatment of post-traumatic stress disorder (PTSD) in 2017. Clinical trials are in progress to assess the therapeutic value of psilocybin in MDD and TRD, and in other indications such as cancer-related anxiety and depression, anorexia, PTSD, substance use disorders and various types of chronic pain. The contributors' insights should assist basic and applied science for transition of psychedelics from bench to potential mainstream therapies. The implications are global, because FDA approval of these new medicines will increase international interest and efforts.

Systematic Review of Variables Related to Instruction in Augmentative and Alternative Communication Implementation: Group and Single-Case Design.

PURPOSE: This article provides a systematic review and analysis of group and single-case studies addressing augmentative and alternative communication (AAC) intervention with school-aged persons having autism spectrum disorder (ASD) and/or intellectual/developmental disabilities resulting in complex communication needs (CCNs). Specifically, we examined participant characteristics in group-design studies reporting AAC intervention outcomes and how these compared to those reported in single-case experimental designs (SCEDs). In addition, we compared the status of intervention features reported in group and SCED studies with respect to instructional strategies utilized. PARTICIPANTS: Participants included school-aged individuals with CCNs who also experienced ASD or ASD with an intellectual delay who utilized aided or unaided AAC. METHOD: A systematic review using descriptive statistics and effect sizes was implemented. RESULTS: Findings revealed that participant features such as race, ethnicity, and home language continue to be underreported in both SCED and group-design studies. Participants in SCED investigations more frequently used multiple communication modes when compared to participants in group studies. The status of pivotal skills such as imitation was sparsely reported in both types of studies. With respect to instructional features, group-design studies were more apt to utilize clinical rather than educational or home settings when compared with SCED studies. In addition, SCED studies were more apt to utilize instructional methods that closely adhered to instructional features more typically characterized as being associated with behavioral approaches. CONCLUSION: The authors discuss future research needs, practice implications, and a more detailed specification of treatment intensity parameters for future research.