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Older age is associated with worsened outcome after mild traumatic brain injury (mTBI) and a higher risk of developing persistent post-traumatic complaints. However, the effects of mTBI sequelae on brain connectivity at older age and their association with post-traumatic complaints remain understudied.We analyzed multi-echo resting-state functional magnetic resonance imaging data from 25 older adults with mTBI (mean age: 68 years, SD: 5 years) in the subacute phase (mean injury to scan interval: 38 days, SD: 9 days) and 20 age-matched controls. Severity of complaints (e.g. fatigue, dizziness) was assessed using self-reported questionnaires. Group independent component analysis was used to identify intrinsic connectivity networks (ICNs). The effects of group and severity of complaints on ICNs were assessed using spatial maps intensity (SMI) as a measure of within-network connectivity, and (static) functional network connectivity (FNC) as a measure of between-network connectivity.Patients indicated a higher total severity of complaints than controls. Regarding SMI measures, we observed hyperconnectivity in left-mid temporal gyrus (cognitive-language network) and hypoconnectivity in the right-fusiform gyrus (visual-cerebellar network) that were associated with group. Additionally, we found interaction effects for SMI between severity of complaints and group in the visual(-cerebellar) domain. Regarding FNC measures, no significant effects were found.In older adults, changes in cognitive-language and visual(-cerebellar) networks are related to mTBI. Additionally, group-dependent associations between connectivity within visual(-cerebellar) networks and severity of complaints might indicate post-injury (mal)adaptive mechanisms, which could partly explain post-traumatic complaints (such as dizziness and balance disorders) that are common in older adults during the subacute phase.

Funder: Wellcome Clinical PhD fellowship, Funder: Wellcome PhD Studentship, Funder: Jean Shank/Pathological Society Intermediate Fellowship, Mutation accumulation in somatic cells contributes to cancer development and is proposed as a cause of aging. DNA polymerases Pol ε and Pol δ replicate DNA during cell division. However, in some cancers, defective proofreading due to acquired POLE/POLD1 exonuclease domain mutations causes markedly elevated somatic mutation burdens with distinctive mutational signatures. Germline POLE/POLD1 mutations cause familial cancer predisposition. Here, we sequenced normal tissue and tumor DNA from individuals with germline POLE/POLD1 mutations. Increased mutation burdens with characteristic mutational signatures were found in normal adult somatic cell types, during early embryogenesis and in sperm. Thus human physiology can tolerate ubiquitously elevated mutation burdens. Except for increased cancer risk, individuals with germline POLE/POLD1 mutations do not exhibit overt features of premature aging. These results do not support a model in which all features of aging are attributable to widespread cell malfunction directly resulting from somatic mutation burdens accrued during life.

Purpose: Early evidence supports the safety and efficiency of extended scope speech-language pathology (SLP) clinics designed to manage low risk ear nose and throat (ENT) outpatient referrals, howe...

Tephritid fruit flies are major economic pests for fruit production and are an impediment to international trade. Different host fruits are known to vary in their suitability for fruit flies to complete their life cycle. Currently, international regulatory standards that define the likely legal host status for tephritid fruit flies categorize fruits as a natural host, a conditional host, or a nonhost. For those fruits that are natural or conditional hosts, infestation rate can vary as a spectrum ranging from highly attractive fruits supporting large numbers of fruit flies to very poor hosts supporting low numbers. Here, we propose a Host Suitability Index (HSI), which divides the host status of natural and conditional hosts into five categories based on the log infestation rate (number of flies per kilogram of fruit) ranging from very poor (100). Infestation rates may be determined by field sampling or cage infestation studies. We illustrate the concept of this index using 21 papers that examine the host status of fruits in five species of polyphagous fruit flies in the Pacific region: Bactrocera tryoni Froggatt, Bactrocera dorsalis (Hendel), Bactrocera latifrons (Hendel), Zeugodacus cucurbitae (Coquillett), and Ceratitis capitata (Wiedemann) (Diptera: Tephritidae). This general-purpose index may be useful in developing systems approaches that rely on poor host status, for determining surveillance and detection protocols for potential incursions, and to guide the appropriate regulatory response during fruit fly outbreaks.

Objectives: Tourette syndrome (TS) is characterized by the presence of sudden, rapid movements and vocalizations (tics). The nature of tics suggests impairments in inhibitory control. However, findings of impaired inhibitory control have so far been inconsistent, possibly due to small sample sizes, wide age ranges, or not taking medication use or attention-deficit/hyperactivity disorder (ADHD) comorbidity into account. Methods: We investigated group differences in response inhibition using an fMRI-based stop-signal task in 103 8-12-year-old children (n = 51 with TS, of whom n = 28 without comorbid ADHD [TS–ADHD] and n = 23 with comorbid ADHD [TS + ADHD]; and n = 52 healthy controls), and related these measures to tic and ADHD severity. Results: We observed an impaired response inhibition performance in children with TS + ADHD, but not in those with TS–ADHD, relative to healthy controls, as evidenced by a slower stop-signal reaction time, slower mean reaction times, and larger variability of reaction times. Dimensional analyses implicated ADHD severity as the driving force in these findings. Neural activation during failed inhibition was stronger in the inferior frontal gyrus and temporal and parietal areas in TS + ADHD compared to healthy controls. Conclusions: Impaired inhibitory performance and increased neural activity in TS appear to manifest predominantly in relation to ADHD symptomatology.

Introduction: Rapid diagnosis of M. tuberculosis directly from sputum samples is a challenging process. This study aimed to design and evaluate a multiplex-PCR method for direct diagnosis of M. tuberculosis from sputum specimens. Materials and Methods: 46 suspected tuberculosis patients and 25 apparently healthy individuals were enrolled in the study. Sputa were collected from the study population and processed by cold ZN stain. DNA was extracted from each sample and processed by Multiplex PCR and Genotype Mycobacteria CM. Results: Out of the 46 Tuberculosis suspected patients, 22 (47.8%) revealed positive Acid fast ba- cilli (AFB), while 19 (41.3%) showed positive by both multiplex PCR and Genotype Mycobacte- ria CM. The overall sensitivity of multiplex PCR and smear microscopy were 100% while the specificity were 100, and 86.3%, respectively. Conclusion: Multiplex PCR method using two different sets of primers in combination with other diagnostic tools such as X-Rays and smear Microscopy are cheap, rapid and reliable methods for the diagnosis of M. tuberculosis from clinical samples and are able to identify most of the smear positive cases with valuable accuracy.

Aim Children with middle ear disease often experience lengthy delays waiting for outpatient paediatric ear nose and throat (ENT) services. This study aimed to investigate whether an alternative service delivery model using audiologists working in an expanded scope of practice reduced waiting times for children to access such services. Methods A total of 131 children consecutively referred to a large ENT outpatient service in Queensland, Australia, for middle ear and hearing concerns were prospectively allocated to either a standard ENT service or an advanced audiology (AA)-led service. Waiting times and attendance rates were collected and compared between the two patient groups. Results The median waiting time from referral to first offered appointment was 96 days for children in the AA-led service versus 417.5 days for children in the standard ENT service. Seventy-nine percent of children in the AA-led service attended their first offered appointment versus 61% in the standard ENT service. For children receiving grommets, the median waiting time from initial referral to grommet insertion was 226 days for children in the AA-led service versus 627 days for children in the standard ENT service. Conclusion The AA-led service was an effective alternative pathway to reduce waiting times for children referred to ENT services with middle ear and hearing concerns.

Setting This paper documents a participatory process of Health Portfolio staff in the design of a clock, and announces the 2020 Canadian Health Clock, with links to numerous online health calculators. The clock is part of the Health Portfolio’s celebration activities in 2019 of “100 Years of Health”, as the Department of Health was established in Canada in 1919. Intervention The intervention was the development of a clock on the Government of Canada website with linkage to calculators as a health promotion tool. The clock was built on the concept of the 2004 Chronic Disease Clock, which shows the number of deaths so far today, and so far this year. The clock was developed using a consultative approach, following a review of the original clock. Outcomes The 2020 clock incorporates new data visualization concepts. New features, facilitated by improved technology, include: expansion to all causes of death; blinking red dots to enhance visual impact; and three clock versions (analogue, featuring a moving circle; digital, table format; and graphical, bar chart format). The clock also provides links to a number of health calculators, to allow people to seek personalized information to improve their health. Implications The online health clock and health calculators are good examples of innovation in health risk communication tools for effective knowledge translation and dissemination. They inform people about health statistics (clock) and their health (calculators). The clock engages people in the context of the Canadian population, whereas the calculators provide personalized information about improving an individual’s future health.

Introduction: Sickle Cell Disease (SCD) is an inherited haemolytic disorder that affects virtually all body systems including the eye. Ocular complications of SCD could have dire consequences if not detected early. Objectives: We aimed at determining the prevalence of ocular complications of SCD in our patients. Methods: This study was carried out on patients attending both the adult and Paediatric Sickle cell disease clinic at Chukwuemeka Odumegwu Ojukwu Teaching Hospital, Akwa, Anambra State, Nigeria, over an 8 month period. A structured questionnaire was administered to consenting patients to determine their sociodemographic variables and other characteristics. Visual acuity was determined with multiple optotype Snellen’s chart at 6 metres in natural daylight. Using pen-torch, the face, external eye examination, anterior segment examination and pupillary reaction to light were assessed. Magnified anterior segment examination was performed with slit-lamp biomicroscope. All subjects underwent dilated fundoscopy (after instillation of tropicamide 0.5% eye drop) using Welch Allyn indirect ophthalmoscope. Results were analysed using SPSS version 22.0 Inc Chicago Illinois and represented in tables. Statistically significant P value was set at < 0.05. Results: A total of 28 patients with age range of 6-42 years were seen. 17 (60.7%) were males, while 11 (39.3%) were females. 8 (28.6%) had at least one ocular anomaly comprising of refractory errors 3 (10.8%), sickle cell retinopathy 4 (14.3%) and glaucoma 2 (7.1%). Only 2 (7.1%) routinely visit eye clinic. SCD retinopathy was found to increase with age (P value= 0.005). Conclusion: SCD retinopathy was found more in the older age group despite the small sample size at a prevalence rate of 14.3%. Early initiation of routine ocular examination for SCD patients will be beneficial to avert these complications. More efforts should be made at educating the patients. Larger studies will be required to determine the actual prevalence of ocular anomaly in SCD patients in Anambra State.

OBJECTIVES: Expansion of the scopes of practice of allied health practitioners has the potential to improve the efficiency and cost-effectiveness of healthcare, given the identified shortages in medical personnel. Despite numerous examples in other allied health disciplines, this has yet to be applied to pediatric Audiology. This study aimed to investigate the effectiveness and safety of using audiologists with advanced training to independently triage children referred to otolaryngology (ORL) services, and compare the subsequent use of specialist resources, and postoperative grommet care to a standard medical ORL service. DESIGN: One hundred twenty children consecutively referred to a large ORL outpatient service in Queensland, Australia, for middle ear and hearing concerns were prospectively allocated to either the ORL service or Advanced Audiology-led service. Demographic and clinical data were extracted from electronic medical records and compared between the two services. Clinical incidents and adverse events were recorded for the Advanced Audiology-led service. RESULTS: Approximately half of all children referred to ORL for middle ear or hearing concerns were discharged without requiring any treatment, with the remaining half offered surgical treatment. The Advanced Audiology-led model increased the proportion of children assessed by ORL that proceeded to surgery from 57% to 82% compared with the standard medical ORL model. Children followed up by the audiologists after grommet insertion were more likely to be discharged independently and at the first postoperative review appointment compared with the standard medical ORL service. There were no reports of adverse events or long-term bilateral hearing loss after discharge by the Advanced Audiology-led service. CONCLUSIONS: These findings indicate that an Advanced Audiology-led service provides a safe and effective triaging model for the independent management of children not requiring treatment, and children requiring routine postoperative grommet review, and improves the effective use of specialist resource compared with the standard medical ORL service.

The mammalian intestine is colonized by trillions of microorganisms that have co-evolved with the host in a symbiotic relationship. The presence of large numbers of symbionts near the epithelial surface of the intestine poses an enormous challenge to the host because it must avoid the activation of harmful inflammatory responses to the microorganisms while preserving its ability to mount robust immune responses to invading pathogens. In patients with inflammatory bowel disease, there is a breakdown of the multiple strategies that the immune system has evolved to promote the separation between symbiotic microorganisms and the intestinal epithelium and the effective killing of penetrant microorganisms, while suppressing the activation of inappropriate T cell responses to resident microorganisms. Understanding the complex interactions between intestinal microorganisms and the host may provide crucial insight into the pathogenesis of inflammatory bowel disease as well as new avenues to prevent and treat the disease.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3004 unmedicated healthy individuals (12–68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r = 0.067, pFDR = 0.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r = 0.285, pspin = 0.024), but not BD (r = 0.166, pspin = 0.205) or MDD (r = −0.274, pspin = 0.073). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho = −0.690, pspin = 0.006), BD (rho = −0.672, pspin = 0.009), and MDD (rho = −0.692, pspin = 0.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

Purpose: There is a need for more intuitive perimetric screening methods, which can also be performed by elderly people and children currently unable to perform standard automated perimetry (SAP). Ideally, these methods should also be easier to administer, such that they may be used outside of a regular clinical environment. We evaluated the suitability of various methodological and analytical approaches for detecting and localizing VFD in glaucoma patients, based on eye movement recordings.Methods: The present study consisted of two experiments. In experiment 1, we collected data from 20 glaucoma patients and 20 age-matched controls, who monocularly viewed 28 1-min video clips while their eyes were being tracked. In experiment 2, we re-analyzed a published dataset, that contained data of 44 glaucoma patients and 32 age-matched controls who had binocularly viewed three longer-duration (3, 5, and 7 min) video clips. For both experiments, we first examined if the two groups differed in the basic properties of their fixations and saccades. In addition, we computed the viewing priority (VP) of each participant. Following a previously reported approach, for each participant, we mapped their fixation locations and used kernel Principal Component Analysis (kPCA) to distinguish patients from controls. Finally, we attempted to reconstruct the location of a patient's VFD by mapping the relative fixation frequency and the VP across their visual field.Results: We found direction dependent saccade amplitudes in glaucoma patients that often differed from those of the controls. Moreover, the kPCA indicated that the fixation maps of the two groups separated into two clusters based on the first two principal components. On average, glaucoma patients had a significantly lower VP than the controls, with this decrease depending on the specific video viewed.Conclusions: It is possible to detect the presence of VFD in glaucoma patients based on their gaze behavior made during video viewing. While this corroborates earlier conclusions, we show that it requires participants to view the videos monocularly. Nevertheless, we could not reconstruct the VFD with any of the evaluated methods, possibly due to compensatory eye movements made by the glaucoma patients.

Cellular DNA damage caused by reactive oxygen species is repaired by the base excision repair (BER) pathway which includes the DNA glycosylase MUTYH. Inherited biallelic MUTYH mutations cause predisposition to colorectal adenomas and carcinoma. However, the mechanistic progression from germline MUTYH mutations to MUTYH-Associated Polyposis (MAP) is incompletely understood. Here, we sequenced normal tissue DNAs from 10 individuals with MAP. Somatic base substitution mutation rates in intestinal epithelial cells were elevated 2 to 5-fold in all individuals, except for one showing a 33-fold increase, and were also increased in other tissues. The increased mutation burdens were of multiple mutational signatures characterised by C>A changes. Different mutation rates and signatures between individuals were likely due to different MUTYH mutations or additional inherited mutations in other BER pathway genes. The elevated base substitution rate in normal cells likely accounts for the predisposition to neoplasia in MAP. Despite ubiquitously elevated mutation rates, individuals with MAP do not display overt evidence of premature ageing. Thus, accumulation of somatic mutations may not be sufficient to cause the global organismal functional decline of ageing.Summary

Incomplete spinal cord injury (SCI) may result in muscle weakness and difficulties with force gradation. Although these impairments arise from the injury and subsequent changes at spinal levels, changes have also been demonstrated in the brain. Blood-oxygen-level dependent (BOLD) imaging was used to investigate these changes in brain activation in the context of unimanual contractions with the first dorsal interosseous muscle. BOLD- and force data were obtained in 19 individuals with SCI (AISA Impairment Scale [AIS] C/D, level C4-C8) and 24 able-bodied controls during maximal voluntary contractions (MVCs). To assess force modulation, participants performed 12 submaximal contractions with each hand (at 10, 30, 50, and 70% MVC) by matching their force level to a visual target. MVCs were weaker in the SCI group (both hands p < 0.001), but BOLD activation did not differ between SCI and control groups. For the submaximal contractions, force (as %MVC) was similar across groups. However, SCI participants showed increased activity of the ipsilateral motor cortex and contralateral cerebellum across all contractions, with no differential effect of force level. Activity of ipsilateral M1 was best explained by force of the target hand (vs. the non-target hand). In conclusion, the data suggest that after incomplete cervical SCI, individuals remain capable of producing maximal supraspinal drive and are able to modulate this drive adequately. Activity of the ipsilateral motor network appears to be task related, although it remains uncertain how this activity contributes to task performance and whether this effect could potentially be harnessed to improve motor functioning.

Background: Impaired clinical and cognitive insight are prevalent in schizophrenia and relate to poorer outcome. Good insight has been suggested to depend on social cognitive and metacognitive abilities requiring global integration of brain signals. Impaired insight has been related to numerous focal gray matter (GM) abnormalities distributed across the brain suggesting dysconnectivity at the global level. In this study, we test whether global integration deficiencies reflected in gray matter network connectivity underlie individual variations in insight.Methods: We used graph theory to examine whether individual GM-network metrics relate to insight in patients with a psychotic disorder (n = 114). Clinical insight was measured with the Schedule for the Assessment of Insight & ndash;Expanded and item G12 of the Positive and Negative Syndrome Scale, and cognitive insight with the Beck Cognitive Insight Scale. Individual GM-similarity networks were created from GM-segmentations of T1weighted MRI-scans. Graph metrics were calculated using the Brain Connectivity Toolbox.Results: Networks of schizophrenia patients with poorer clinical insight showed less segregation (i.e. clustering coefficient) into specialized subnetworks at the global level. Schizophrenia patients with poorer cognitive insight showed both less segregation and higher connectedness (i.e. lower path length) of their brain networks, making their network topology more & ldquo;random & rdquo;.Conclusions: Our findings suggest less segregated processing of information in patients with poorer cognitive and clinical insight, in addition to higher connectedness in patients with poorer cognitive insight. The ability to take a critical perspective on one & rsquo;s symptoms (clinical insight) or views (cognitive insight) might depend especially on segregated specialized processing within distinct subnetworks.

The advanced audiology-led service is designed to triage and manage children who are referred to Ear Nose and Throat (ENT) outpatient services with middle ear or hearing concerns. This service has resulted in shorter waiting times for children to receive ENT treatment, and improved ENT capacity. The aim of this study was to explore parental satisfaction with the advanced audiology-led ENT service and to determine if there were cultural or process factors affecting satisfaction.Prospective cross-sectional study using a modified Visit-Specific Satisfaction Questionnaire (VSQ-9) survey.One hundred and thirteen parents of children consecutively attending a first appointment in the advanced audiology-led service recruited between October 2016 and October 2017.There were a total of 100 valid responses (rate of 88.5%). The survey showed high levels of satisfaction. Satisfaction scores were significantly higher for items related to interactions with the audiologist compared to items related to waiting times. There were no differences in satisfaction across cultural groups. Parents were equally satisfied with the service whether their child was managed independently by the audiologist or required another appointment for medical input.The advanced audiology-led service had high levels of satisfaction from parents attending with their children.

Although much research has been devoted to the neural correlates of motion perception, the processing of speed of motion is still a topic of discussion. Apart from patient LM, no in-depth clinical research has been done in the past 20 years on this topic. In the present study, we investigated patient TD, who suffered from the rare disorder akinetopsia due to bilateral lesions of V5 after stroke. By means of a Random-Dot-Kinematogram (RDK) in which speed was varied systematically, it was found that TD was impaired in perceiving the direction of movement at speeds exceeding 9 deg/s. Our study suggests that V5 plays an important role in processing high-speed visual motion and further implies that V5 does not play a crucial role in processing low-speed visual motion. A remarkable finding, which has not been shown before, was that TD always reported the opposite direction of the actual movement at a speed of 24 deg/s. This suggests a form of the continuous wagon wheel illusion, which might have been caused by intact brain areas operating at different sampling rates than area V5.

Individuals with psychosis are at an increased risk of victimization. Processing of facial expressions has been suggested to be associated with victimization in this patient group. Especially processing of angry expressions may be relevant in the context of victimization. Therefore, differences in brain activation and connectivity between victimized and nonvictimized patients during processing of angry faces were investigated. Thirty-nine patients, of whom nineteen had experienced threats, assaults, or sexual violence in the past 5 years, underwent fMRI scanning, during which they viewed angry and neutral facial expressions. Using general linear model (GLM) analyses, generalized psychophysiological (gPPI) analysis and independent component analyses (ICA) differences in brain activation and connectivity between groups in response to angry faces were investigated. Whereas differences in regional brain activation GLM and gPPI analyses yielded no differences between groups, ICA revealed more deactivation of the sensorimotor network in victimized participants. Deactivation of the sensorimotor network in response to angry faces in victimized patients, might indicate a freeze reaction to threatening stimuli, previously observed in traumatized individuals.

The aim of this study was to investigate whether apathy in schizophrenia is associated with rigidity in behavior and brain functioning. To this end, we studied associations between variability in dynamic functional connectivity (DFC) in relevant functional brain networks, apathy, and variability in physical activity in schizophrenia. Thirty-one patients with schizophrenia, scoring high on apathy, were included and wore an actigraph. Activity variability was calculated on the activity counts using the root of the Mean Squared Successive Difference (MSSD). Furthermore, we calculated DFC on resting-state data as phase interactions between blood oxygen-level dependent (BOLD) signals of 270 brain regions per volume. Variability (MSSD) in DFC was calculated for 3 networks, including the default-mode network (DMN), frontoparietal network, and salience-reward network (SRN). Finally, we calculated correlations between these DFC estimates and apathy and activity variability. First, lower activity variability was associated with higher levels of apathy. Second, higher levels of apathy were associated with lower variability in DFC in the DMN and SRN. Third, higher activity variability was associated with higher variability in DFC in the SRN. In conclusion, patients with schizophrenia and more severe levels of apathy showed less variability in their physical activity and more rigid functional brain network behavior in the DMN and SRN. These networks have been shown relevant for self-reflection, mental simulation, and reward processing, processes that are pivotal for self-initiated goal-directed behavior. Functional rigidity of these networks may therefore contribute to reduced goal-directed behavior, which is characteristic for these patients.

To describe growth evolution and its correlates in the first 5 years of antiretroviral therapy (ART) initiation among HIV-infected children followed up in West Africa.All HIV-infected children younger than 10 years followed in the IeDEA pWADA cohort while initiating ART, with at least one anthropometric measurement within the first 5 years of treatment were included in the study. Growth was described according to the WHO child growth standards, using Weight-for-age Z-score (WAZ), Height-for-age Z-score (HAZ) and Weight-for-Height/BMI-for-age Z-score (WHZ/BAZ). Growth evolution and its correlates, measured at ART initiation, were modelled in individual linear mixed models for each anthropometric indicator, with a spline term added at the 12-, 24- and 9-month time point for WAZ, HAZ and WHZ/BAZ, respectively.Among the 4156 children selected (45% girls, median age at ART initiation 3.9 years [IQR interquartile range 1.9-6.6], and overall 68% malnourished at ART initiation), important gains were observed in the first 12, 24 and 9 months on ART for WAZ, HAZ and WHZ/BAZ, respectively. Correlates at ART initiation of a better growth evolution overtime were early age (2 years of age), severe immunodeficiency for age, and severity of malnutrition.Growth evolution is particularly strong within the first 2 years on ART but slows down after this period. Weight and height gains help to recover from pre-ART growth deficiency but are insufficient for the most severely malnourished. The first year on ART could be the best period for nutritional interventions to optimize growth among HIV-infected children in the long-term.Décrire l’évolution de la croissance et ses corrélats au cours des cinq premières années d'initiation du traitement antirétroviral (ART) chez les enfants infectés par le VIH, suivis en Afrique de l'Ouest. MÉTHODES: Tous les enfants infectés par le VIH âgés de moins de 10 ans suivis dans la cohorte IeDEA pWADA au début de l’ART, avec au moins une mesure anthropométrique au cours des cinq premières années de traitement, ont été inclus dans l’étude. La croissance a été décrite selon les normes de croissance de l'enfant de l’OMS, en utilisant le Z-score Poids pour l’âge (WAZ), le Z-score Taille pour l’âge (HAZ) et le Z-score Poids-pour-Taille/IMC pour l’âge (WHZ/BAZ). L’évolution de la croissance et ses corrélats, mesurés au début de l’ART, ont été modélisés dans des modèles mixtes linéaires individuels pour chaque indicateur anthropométrique, avec un terme spline ajouté aux points 12, 24 et 9 mois pour WAZ, HAZ et WHZ/BAZ respectivement. RÉSULTATS: Parmi les 4.156 enfants sélectionnés (45% de filles, âge médian au début l’ART 3,9 ans [intervalle interquartile IQR de 1,9 à 6,6] et au total 68% de malnutrition au début de l’ART), des gains importants ont été observés dans les 12, 24 et 9 premiers mois sous ART pour WAZ, HAZ et WHZ/BAZ respectivement. Les corrélats au début de l’ART pour une meilleure évolution de la croissance au cours du temps étaient: l’âge précoce (2 ans), un déficit immunitaire sévère pour l’âge et la sévérité de la malnutrition.L’évolution de la croissance est particulièrement forte au cours des deux premières années sous ART, mais ralentit après cette période. Les gains de poids et de taille aident à récupérer du retard de croissance pré-ART mais sont insuffisants pour les plus sévèrement malnutris. La première année sous ART pourrait être la meilleure période pour les interventions nutritionnelles visant à optimiser la croissance à long terme des enfants infectés par le VIH.

The cytokine IL-22 is rapidly induced at barrier surfaces where it regulates host-protective antimicrobial immunity and tissue repair but can also enhance disease severity in some chronic inflammatory settings. Using the chronic Salmonella gastroenteritis model, Ab-mediated neutralization of IL-22 impaired intestinal epithelial barrier integrity and, consequently, exaggerated expression of proinflammatory cytokines. As disease normally resolved, neutralization of IL-22 caused luminal narrowing of the cecum—a feature reminiscent of fibrotic strictures seen in Crohn disease patients. Corresponding to the exaggerated immunopathology caused by IL-22 suppression, Salmonella burdens in the gut were reduced. This enhanced inflammation and pathogen clearance was associated with alterations in gut microbiome composition, including the overgrowth of Bacteroides acidifaciens. Our findings thus indicate that IL-22 plays a protective role by limiting infection-induced gut immunopathology but can also lead to persistent pathogen colonization.

Neuroanatomical abnormalities have been reported along a continuum from at-risk stages, including high schizotypy, to early and chronic psychosis. However, a comprehensive neuroanatomical mapping of schizotypy remains to be established. The authors conducted the first large-scale meta-analyses of cortical and subcortical morphometric patterns of schizotypy in healthy individuals, and compared these patterns with neuroanatomical abnormalities observed in major psychiatric disorders. The sample comprised 3,004 unmedicated healthy individuals (12-68 years, 46.5% male) from 29 cohorts of the worldwide ENIGMA Schizotypy working group. Cortical and subcortical effect size maps with schizotypy scores were generated using standardized methods. Pattern similarities were assessed between the schizotypy-related cortical and subcortical maps and effect size maps from comparisons of schizophrenia (SZ), bipolar disorder (BD) and major depression (MDD) patients with controls. Thicker right medial orbitofrontal/ventromedial prefrontal cortex (mOFC/vmPFC) was associated with higher schizotypy scores (r=.07, pFDR=.02). The cortical thickness profile in schizotypy was positively correlated with cortical abnormalities in SZ (r=.33, pspin=.01), but not BD (r=.19, pspin=.16) or MDD (r=-.22, pspin=.10). The schizotypy-related subcortical volume pattern was negatively correlated with subcortical abnormalities in SZ (rho=-.65, pspin=.01), BD (rho=-.63, pspin=.01), and MDD (rho=-.69, pspin=.004). Comprehensive mapping of schizotypy-related brain morphometry in the general population revealed a significant relationship between higher schizotypy and thicker mOFC/vmPFC, in the absence of confounding effects due to antipsychotic medication or disease chronicity. The cortical pattern similarity between schizotypy and schizophrenia yields new insights into a dimensional neurobiological continuity across the extended psychosis phenotype.

Purpose: To solve complex health issues, an innovative and multidisciplinary framework is necessary. The Clinical Public Health (CPH) Division was established at the University of Toronto (UofT), Canada to foster inte-gration of primary care, preventive medicine and public health in education, practice and research. To better understand how the construct of CPH might be applied, we surveyed clinicians, researchers and public health professionals affiliated with the CPH Division to assess their understanding of the CPH concept and its utility in fostering broad collaboration. Methods: A two-wave anonymous survey of the active faculty of the CPH Division, UofT was conducted across Canada. Wave 1 participants (n = 187; 2016) were asked to define CPH, while Wave 2 participants (n = 192; 2017) were provided a synthesis of Wave 1 results and asked to rank each definition. Both waves were asked about the need for a common definition, and to comment on CPH. Results: Response rates for the first and second waves were 25% and 22%, respectively. Of the six definitions of CPH from Wave 1, “the intersection of clinical practice and public health,” was most highly ranked by Wave 2 participants. Positive perceptions of CPH included multidisciplinary collaboration, new fields and insights, forward thinking and innovation. Negative perceptions included CPH being a confusing term, too narrow in scope or too clinical. Conclusion: The concept of Clinical Public Health can foster multidisciplinary collaboration to address com-plex health issues because it provides a useful framework for bringing together key disciplines and diverse professional specialties.

Experiencing stress can have a disadvantageous effect on mental well-being. Additional to the relation between suffering from chronic stress and depression, both stress (acute and chronic) and depression are associated with cognitive alterations, including working memory. The breakup of a relationship is considered to be a stressful event that can lead to symptoms of depression in otherwise healthy people. Additional to elevated depression scores, stress-related cognitive alterations may occur in this population as well. Therefore, in the present fMRI study we investigated whether experiencing a relationship breakup is associated with working memory alterations and whether this is related to depressive symptom severity. A three workload version of the n-back task (0-back, 1-back, 2-back) was used to measure working memory in subjects who experienced a breakup in the preceding 6 months (“heartbreak group”, n = 70) and subjects in a romantic relationship (“relationship group”, n = 46). Behavioral task performance was compared between the two groups. Functional MRI scans were analyzed using General Linear Model (GLM) activation analyses. Workload conditions were contrasted to each other and to baseline and group differences were assessed. To investigate whether brain networks are associated with depressive symptom severity within the heartbreak group specifically, a post hoc feature-based Independent Component Analysis was performed on the 2-back > 0-back contrast images to identify brain regions that covaried across subjects. Behaviorally, the heartbreak group performed similar at high workload (i.e., 2-back) and better at moderate workload (i.e., 1-back) than the relationship group. GLM analysis revealed an interaction between group and 2-back > 0-back, 2-back > 1-back and 2-back > baseline; the heartbreak group showed less precuneus activation compared to the relationship group. Furthermore, within the heartbreak group, we found a negative association between depressive symptom severity and a brain network representing mostly the precuneus, anterior cingulate gyrus and supplementary motor cortex. Our findings suggest that the effect of a breakup is accompanied by workload-dependent working memory alterations. Therefore, we propose that this population can potentially be used to investigate the interplay between stress, cognitive functioning and depression.

Individuals with a psychotic disorder are at an increased risk of becoming the victim of a crime. A body-oriented resilience therapy (BEATVIC) aimed at preventing victimization by addressing putatively underlying factors was developed. One of these factors is social cognition, particularly facial affect processing. The current study investigated neural effects of BEATVIC on facial affect processing using two face processing tasks. Participants were randomized to either BEATVIC or a ‘Befriending’ control group. Twenty-seven patients completed an Emotional Faces task and the Wall of Faces task during fMRI, pre- and post-intervention. General linear model analyses yielded no differences between groups over time. Independent component analyses revealed increased activation of the salience network to angry and fearful faces in BEATVIC compared to Befriending. Increased activation of the salience network may suggest an increased alertness for potentially dangerous faces. Electronic supplementary material The online version of this article (10.1007/s00406-020-01097-z) contains supplementary material, which is available to authorized users.

BACKGROUND The transition to dolutegravir-containing antiretroviral therapy (ART) in low- and middle-income countries (LMICs) was complicated by an initial safety signal in May 2018 suggesting that exposure to dolutegravir at conception was possibly associated with infant neural tube defects. On the basis of additional evidence, in July 2019, the World Health Organization recommended dolutegravir for all adults and adolescents living with HIV. OBJECTIVE To describe dolutegravir uptake and disparities by sex and age group in LMICs. DESIGN Observational cohort study. SETTING 87 sites that began using dolutegravir in 11 LMICs in the Asia-Pacific; Caribbean, Central and South America network for HIV epidemiology (CCASAnet); and sub-Saharan African regions of the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium. PATIENTS 134��672 patients aged 16 years or older who received HIV care from January 2017 through March 2020. MEASUREMENTS Sex, age group, and dolutegravir uptake (that is, newly initiating ART with dolutegravir or switching to dolutegravir from another regimen). RESULTS Differences in dolutegravir uptake among females of reproductive age (16 to 49 years) emerged after the safety signal. By the end of follow-up, the cumulative incidence of dolutegravir uptake among females 16 to 49 years old was 29.4% (95% CI, 29.0% to 29.7%) compared with 57.7% (CI, 57.2% to 58.3%) among males 16 to 49 years old. This disparity was greater in countries that began implementing dolutegravir before the safety signal and initially had highly restrictive policies versus countries with a later rollout. Dolutegravir uptake was similar among females and males aged 50 years or older. LIMITATION Follow-up was limited to 6 to 8 months after international guidelines recommended expanding access to dolutegravir. CONCLUSION Substantial disparities in dolutegravir uptake affecting females of reproductive age through early 2020 are documented. Although this disparity was anticipated because of country-level restrictions on access, the results highlight its extent and initial persistence. PRIMARY FUNDING SOURCE National Institutes of Health.

Highlights • Post-mTBI fatigue relates to visual processing and effort perception. • Fatigue correlates with activity in the extrastriate cortex and left midcingulate. • CNS drive during a sustained effort correlates with post-contraction BOLD-activity. • Insular and midcingulate activation suggests changes in cortical homeostasis., Introduction Following mild traumatic brain injury (mTBI), a substantial number of patients experience disabling fatigue for months after the initial injury. To date, the underlying mechanisms of fatigue remain unclear. Recently, it was shown that mTBI patients with persistent fatigue do not demonstrate increased performance fatigability (i.e., objective performance decline) during a sustained motor task. However, it is not known whether the neural activation required to sustain this performance is altered after mTBI. Methods Blood oxygen level-dependent (BOLD) fMRI data were acquired from 19 mTBI patients (>3 months post-injury) and 19 control participants during two motor tasks. Force was recorded from the index finger abductors of both hands during submaximal contractions and a 2-minute maximal voluntary contraction (MVC) with the right hand. Voluntary muscle activation (i.e., CNS drive) was indexed during the sustained MVC using peripheral nerve stimulation. Fatigue was quantified using the Fatigue Severity Scale (FSS) and Modified Fatigue Impact Scale (MFIS). Questionnaire, task, and BOLD data were compared across groups, and linear regression was used to evaluate the relationship between BOLD-activity and fatigue in the mTBI group. Results The mTBI patients reported significantly higher levels of fatigue (FSS: 5.3 vs. 2.6, p