A P2RY12 deficiency results in sex-specific cellular perturbations and sexually dimorphic behavioral anomalies.

Microglia are sexually dimorphic, yet, this critical aspect is often overlooked in neuroscientific studies. Decades of research have revealed the dynamic nature of microglial-neuronal interactions, but seldom consider how this dynamism varies with microglial sex differences, leaving a significant gap in our knowledge. This study focuses on P2RY12, a highly expressed microglial signature gene that mediates microglial-neuronal interactions, we show that adult females have a significantly higher expression of the receptor than adult male microglia. We further demonstrate that a genetic deletion of P2RY12 induces sex-specific cellular perturbations with microglia and neurons in females more significantly affected. Correspondingly, female mice lacking P2RY12 exhibit unique behavioral anomalies not observed in male counterparts. These findings underscore the critical, sex-specific roles of P2RY12 in microglial-neuronal interactions, offering new insights into basal interactions and potential implications for CNS disease mechanisms.

A P2RY12 Deficiency Results in Sex-specific Cellular Perturbations and Sexually Dimorphic Behavioral Anomalies.

Microglia are sexually dimorphic, yet, this critical aspect is often overlooked in neuroscientific studies. Decades of research have revealed the dynamic nature of microglial-neuronal interactions, but seldom consider how this dynamism varies with microglial sex differences, leaving a significant gap in our knowledge. This study focuses on P2RY12, a highly expressed microglial signature gene that mediates microglial-neuronal interactions, we show that adult females have a significantly higher expression of the receptor than adult male microglia. We further demonstrate that a genetic deletion of P2RY12 induces sex-specific cellular perturbations with microglia and neurons in females more significantly affected. Correspondingly, female mice lacking P2RY12 exhibit unique behavioral anomalies not observed in male counterparts. These findings underscore the critical, sex-specific roles of P2RY12 in microglial-neuronal interactions, offering new insights into basal interactions and potential implications for CNS disease mechanisms.

Fluorine-18-labelled Prostate-specific Membrane Antigen Positron Emission Tomography/Computed Tomography or Magnetic Resonance Imaging to Diagnose and Localise Prostate Cancer. A Prospective Single-arm Paired Comparison (PEDAL).

BACKGROUND AND OBJECTIVE: Multiparametric magnetic resonance imaging (mpMRI) of the prostate is used for prostate cancer diagnosis. However, mpMRI has lower sensitivity for small tumours. Prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) offers increased sensitivity over conventional imaging. This study aims to determine whether the diagnostic accuracy of 18F-DCFPyL PSMA-PET/CT was superior to that of mpMRI for detecting prostate cancer (PCa) at biopsy. METHODS: Between 2020 and 2021, a prospective multicentre single-arm phase 3 imaging trial enrolled patients with clinical suspicion for PCa to have both mpMRI and PSMA-PET/CT (thorax to thigh), with reviewers blinded to the results of other imaging. Multiparametric MRI was considered positive for Prostate Imaging Reporting and Data System (PIRADS) 3-5. PSMA-PET/CT was assessed quantitatively (positive maximum standardised uptake value [SUVmax] >7) and qualitatively (five-point lexicon of certainty). Patients underwent targeted and systematic biopsy, with the technique at the discretion of the treating urologist. Clinically significant PCa (csPCa) was defined as International Society of Urological Pathology grade group (GG) ≥2. The primary outcome was the diagnostic accuracy for detecting PCa, reported as sensitivity, specificity, negative predictive value (NPV), and area under the curve (AUC) of the receiver operating curve. The secondary endpoints included a comparison of the diagnostic accuracy for detecting csPCa, assessing gains in combining PMSA-PET/CT with mpMRI to mpMRI alone. KEY FINDINGS AND LIMITATIONS: Of the 236 patients completing both mpMRI and PSMA-PET/CT, 184 (76.7%) had biopsy. Biopsy histology was benign (n = 73), GG 1 (n = 27), and GG ≥2 (n = 84). The diagnostic accuracy of mpMRI for detecting PCa (AUC 0.76; 95% confidence interval [CI] 0.69, 0.82) was higher than that of PSMA-PET/CT (AUC 0.63; 95% CI 0.56, 0.70, p = 0.03). The diagnostic accuracy of mpMRI for detecting csPCa (AUC 0.72; 95% CI 0.67, 0.78) was higher than that of PSMA-PET/CT (AUC 0.62; 95% CI 0.55, 0.69) but not statistically significant (p = 0.27). A combination of PSMA-PET/CT and mpMRI showed excellent sensitivity (98.8%, 95% CI 93.5%, 100%) and NPV (96%, 95% CI 79.6%, 99.9%) over mpMRI alone (86.9% and 80.7%, respectively, p = 0.01). Thirty-two patients (13.6%) had metastatic disease. They tended to be older (68.4 vs 65.1 yr, p = 0.023), and have higher prostate-specific antigen (PSA; median PSA 9.6 vs 6.2ng/ml, p < 0.001) and abnormal prostate on digital rectal examination (78.2% vs 44.1%, p < 0.001). CONCLUSIONS AND CLINICAL IMPLICATIONS: Multiparametric MRI had superior diagnostic accuracy to PSMA-PET/CT for detecting PCa, though the difference is not significant in case of csPCa detection. A combination of mpMRI and PSMA-PET/CT showed improved sensitivity and NPV. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. PATIENT SUMMARY: In this trial, we compared the ability of 18F-labelled prostate-specific membrane antigen positron emission tomography/computed tomography (PSMA-PET/CT) with that of multiparametric magnetic resonance imaging (mpMRI) to diagnose prostate cancer by biopsy in a prostate-specific antigen screening population. We found that MRI was superior to PSMA to diagnose prostate cancer, though there was no difference in ability to diagnose clinically significant prostate cancer. PSMA-PET/CT could be considered for diagnostic use in patients unable to have mpMRI or those with concerning clinical features but negative mpMRI. Combining MRI with PSMA-PET increases the negative predictive value over MRI alone and may help men avoid invasive prostate biopsy.

Design, fabrication, and evaluation of 3-D-printed cystotomy spoons as a retrieval method in dogs.

OBJECTIVE: Current cystotomy methods often implement the use of off-label devices, resulting in urocystolith extraction difficulty and potentially leading to postoperative complications and discomfort for the patient. The objective of this study was to create 3 novel 3-D printed cystotomy spoons that offer a dedicated solution for removing urocystoliths from a patient's urinary bladder. ANIMALS: Clinical use of the 3 novel 3-D printed cystotomy spoons were ultimately evaluated in 4 dogs and 1 cat that presented for urocystotlith removal at 3 different veterinary hospitals in northwest Arkansas. METHODS: The novel cystotomy spoons were designed using SolidWorks, 3-D printed with a Dental Surgical Guide resin, and underwent prototype testing that included chlorhexidine soaking, autoclave sterilization, 3-point bend testing, and Finite Element Analysis. The efficiency of the spoons was then evaluated through a limited proof-of-concept study utilizing a postoperative questionnaire for the participating clinicians. RESULTS: Practitioner feedback indicated positive experiences using 1 or more of the novel 3-D printed cystotomy spoons while performing a cystotomy surgery. However, successful use of the spoons was ultimately limited to dogs in the 23 to 34 kg weight range. CLINICAL RELEVANCE: Novel 3-D printed cystotomy spoons have the potential to mediate urocystolith extraction difficulty and reduce postoperative complications. Additionally, this research demonstrates how veterinarians might develop custom 3-D models and prints to meet patient-specific needs. As such, further development could impact the standard of healthcare and the veterinary industry by promoting the use of additive manufacturing in veterinary medicine.

Investigating PSMA-PET/CT to resolve prostate MRI PIRADS4-5 and negative biopsy discordance.

BACKGROUND: To determine the utility of diagnostic 18F-DCPyL PSMA-PET/CT to aid management of men with highly suspicious multiparametric MRI prostate (PIRAD 4-5 lesions) and discrepant negative prostate biopsy. METHODS: A multicentre prospective consecutive case series was conducted (2018-2021), recruiting men with prior mpMRI prostate PIRADS 4-5 lesions and negative prostate biopsy. All men had 18F-DCPyL PSMA-PET/CT with subsequent management based on the concordance between MRI and PET: (1) Concordant lesions were biopsied using in-bore MRI targeting; (2) PSMA-PET/CT avidity without MRI correlate were biopsied using cognitive/software targeting with ultrasound guidance and (3) Patients with negative PET/CT were returned to standard of care follow-up. RESULTS: 29 patients were recruited with 48% (n = 14) having concordant MRI/PET abnormalities. MRI targeted biopsy found prostate cancer in six patients, with grade groups GG3 (n = 1), GG2 (n = 1), GG1 (n = 4) found. Of the 20 men who PSMA-PET/CT avidity and biopsy, analysis showed higher SUVmax (20.1 vs 6.8, p = 0.036) predicted prostate cancer. Of patients who had PSMA-PET avidity without MRI correlate, and those with no PSMA-PET avidity, only one patient was subsequently found to have prostate cancer (GG1). The study is limited by small size and short follow-up of 17 months (IQR 12.5-29.9). CONCLUSIONS: PSMA-PET/CT is useful in this group of men but requires further investigation. Avidity (higher SUVmax) that correlates to the mpMRI prostate lesion should be considered for targeted biopsy.

Examination of the COVID-19 Pandemic's Impact on Mental Health From Three Perspectives: Global, Social, and Individual.

The extent of the deleterious effects of the COVID-19 pandemic on mental health is recognized ubiquitously. However, these effects are subject to many modulatory factors from a plethora of domains of examination. It is important to understand the intersection of societal and individual levels for global stressors compared with local phenomena and physical-health outcomes. Here, we consider three perspectives: international/cultural, social, and individual. Both the enduring threat of COVID-19 infection and the protective measures to contain contagion have important consequences on individual mental health. These consequences, together with possible remedial interventions, are the focus of this article. We hope this work will stimulate more research and will suggest factors that need to be considered in the coordination of responses to a global threat, allowing for better preparation in the future.

PEDAL protocol: a prospective single-arm paired comparison of multiparametric MRI and 18F-DCPFyl PSMA PET/CT to diagnose prostate cancer.

INTRODUCTION: Prostate-specific membrane antigen positron emission tomography (PSMA-PET) has emerged as valuable imaging to assessing metastatic disease in prostate malignancy. However, there has been limited studies exploring the utility PSMA-PET as primary imaging assessing for index lesions prior to biopsy. The primary objective of this study is to compare the diagnostic accuracy of 18-fluorine PSMA (18F DCFPyL PSMA) PET scans to multiparametric MRI (mpMRI) to detect primary prostate cancer at prostate biopsy. METHODS AND ANALYSIS: The PEDAL trial is a multicentre, prospective, single-arm, paired comparison, non-randomised phase III trial in subjects considered for diagnostic prostate biopsy. Subjects who are eligible for a diagnostic mpMRI prostate will undergo additional same-day 18 F DCFPyl PSMA PET/CT of the chest, abdomen and pelvis. Software coregistration of the mpMRI and PSMA-PET/CT images will be performed. The reporting of the mpMRI prostate, PSMA-PET/CT and PSMA PET/MRI coregistration will be performed blinded. The diagnostic accuracy of PSMA PET/CT alone, and in combination with mpMRI, to detect prostate cancer will be assessed. Histopathology at prostate biopsy will be used as the reference standard. Sample size calculations estimate that 240 subjects will need to be recruited to demonstrate 20% superiority of PSMA-PET/CT. The sensitivity, specificity, positive predictive value and negative predictive value of the combination of mpMRI prostate and PSMA PET/CT compared with targeted and systematic prostate biopsy will be evaluated. It is hypothesised that PSMA PET/CT combined with mpMRI prostate will have improved diagnostic accuracy compared with mpMRI prostate alone for detection of prostate cancer in biopsy-naïve men, resulting in a significant impact on patient management. ETHICS AND DISSEMINATION: This study was approved by the independent Human Research Ethics Committee. Results will be published in peer-reviewed medical journals with eligible investigators will significantly contribute. TRIAL REGISTRATION NUMBER: ACTRN12620000261910.

Prenatal Exposure to Air Pollution and Early-Life Stress Effects on Hippocampal Subregional Volumes and Associations With Visuospatial Reasoning.

BACKGROUND: Children from economically distressed families and neighborhoods are at risk for stress and pollution exposure and potential neurotoxic sequelae. We examine dimensions of early-life stress affecting hippocampal volumes, how prenatal exposure to air pollution might magnify these effects, and associations between hippocampal volumes and visuospatial reasoning. METHODS: Fifty-three Hispanic/Latinx and/or Black children of ages 7 to 9 years were recruited from a longitudinal birth cohort for magnetic resonance imaging and cognitive assessment. Exposure to airborne polycyclic aromatic hydrocarbons was measured during the third trimester of pregnancy. Maternal report of psychosocial stress was collected at child age 5 and served as measures of early-life stress. Whole hippocampus and subfield volumes were extracted using FreeSurfer. Wechsler performance IQ measured visuospatial reasoning. RESULTS: Maternal perceived stress associated with smaller right hippocampal volume among their children (B = -0.57, t 34 = -3.05, 95% CI, -0.95 to -0.19). Prenatal polycyclic aromatic hydrocarbon moderated the association between maternal perceived stress and right CA1, CA3, and CA4/dentate gyrus volumes (B ≥ 0.68, t 33 ≥ 2.17) such that higher prenatal polycyclic aromatic hydrocarbon exposure magnified negative associations between stress and volume, whereas this was buffered at lower exposure. Right CA3 and CA4/dentate gyrus volumes (B ≥ 0.35, t 33 > 2.16) were associated with greater performance IQ. CONCLUSIONS: Prenatal and early-life exposures to chemical and social stressors are likely compounding. Socioeconomic deprivation and disparities increase risk of these exposures that exert critical neurobiological effects. Developing deeper understandings of these complex interactions will facilitate more focused public health strategies to protect and foster the development of children at greatest risk of mental and physical effects associated with poverty.

Survivors of Acute Lung Injury Have Greater Impairments in Strength and Exercise Capacity Than Survivors of Other Critical Illnesses as Measured Shortly After ICU Discharge.

PURPOSE: To compare the physical function on ICU discharge in adults who survived an ICU admission for acute lung injury (ALI) with those admitted for a critical illness other than ALI. MATERIALS AND METHODS: Two groups were recruited, (i) those who survived an ICU admission for ALI and, (ii) those who survived an ICU admission for a critical illness other than ALI. Within 7 days of discharge from ICU, in all participants, measures were collected of peripheral muscle strength, balance, walking speed and functional exercise capacity. RESULTS: Recruitment was challenging and ceased prior to achieving the desired sample size. Participants with ALI (n = 22) and critical illness (n = 33) were of similar median age (50 vs. 57 yr, p = 0.09), sex proportion (males %, 45 vs. 58, p = 0.59) and median APACHE II score (21.5 vs. 23.0, p = 0.74). Compared with the participants with critical illness, those with ALI had lower hand grip (mean ± SD, 18 ± 9 vs. 13 ± 8 kg, p = 0.018) and shoulder flexion strength (10 ± 4 vs. 7 ± 3 kg, p = 0.047), slower 10-meter walk speed (median [IQR], 1.03 [0.78 to 1.14] vs. 0.78 [0.67 to 0.94] m/s, p = 0.039) and shorter 6-minute walk distance (265 [71 to 328] vs. 165 [53 to 220] m, p = 0.037). The Berg balance scores were similar in both groups. CONCLUSIONS: Compared with survivors of a critical illness that is not ALI, those with ALI are likely to have greater physical impairment when measured shortly after discharge to the ward.

The perceived barriers and facilitators to implementation of early mobilisation within a multicentre, phase 3 randomised controlled trial: A qualitative process evaluation study.

BACKGROUND: Process evaluation within clinical trials provides an assessment of the study implementation's accuracy and quality to explain causal mechanisms and highlight contextual factors associated with variation in outcomes. OBJECTIVES: This study aimed to identify the barriers and facilitators of implementing early mobilisation (EM) within a trial. METHODS: This is a qualitative process evaluation study within the Trial of Early Activity and Mobilisation (TEAM) phase 3 randomised controlled trial. Semistructured interviews were conducted remotely with multiprofessional clinicians (physiotherapists, medical staff, and nursing staff) involved in the delivery of the TEAM intervention at Australian hospitals participating in the TEAM study. Inductive coding was used to establish themes which were categorised into the Behaviour system involving domains of Capability, Opportunity, and Motivation (COM-B), which allowed barriers and enablers affecting EM to be identified. FINDINGS: Semistructured interviews were conducted in three different states of Australia. There were 16 participants, including 10 physiotherapists, five physicians, and one nurse. The key themes that facilitated EM were mentoring, champions, additional staff, organisation of the environment, cultural changes, communication, and documented safety criteria. In contrast, the main factors that hindered EM were lack of expertise and confidence in delivering EM, heavy sedation, interdisciplinary conflicts, and perceived risks related to EM. CONCLUSION: A wide range of barriers and facilitators that influenced EM within the TEAM study were identified using the COM-B framework. Many of these have been previously identified in the literature; however, participation in the study was viewed positively by multidisciplinary team members.

Prenatal exposure to air pollution is associated with childhood inhibitory control and adolescent academic achievement.

BACKGROUND: Prenatal air pollution exposure is associated with reductions in self-regulation and academic achievement. Self-regulation has been separately linked with academic achievement. Understudied, however, are the contributions of pollution exposure to inhibitory control, a facet of self-regulation, and whether pollution-related inhibitory control deficits are associated with impairment in academic achievement. METHODS: Participants were recruited from a prospective birth cohort. Measures of prenatal airborne polycyclic aromatic hydrocarbons (PAH) during the third trimester of pregnancy, inhibitory control (NEPSY Inhibition) at mean age = 10.4 years, and Woodcock-Johnson Tests of Achievement-III at mean age = 13.7 were available for N = 200 participants. Multiple linear regression examined sex-dependent and sex independent associations among prenatal PAH, childhood inhibitory control, and academic achievement during adolescence, and whether childhood inhibitory control mediated associations between prenatal PAH and academic achievement during adolescence, controlling for ethnicity, maternal country of birth, language of prenatal interview, maternal marital status, maternal years of education, material hardship, quality of home caregiving environment, and early life stress. RESULTS: Across all participants, higher prenatal PAH was significantly associated with worse spelling skills (WJ-III Spelling, ß = -0.16, 95%Confidence Interval [CI]: 0.30, -0.02, p = .02). Trend level associations between higher prenatal PAH and worse reading comprehension (WJ-III Passage Comprehension, ß = -0.13, 95%CI: 0.28, 0.01, p = .07) and math skills (WJ-III Broad Math, ß = -0.11, 95%CI: 0.25, 0.03, p = .11) were detected. Across all participants, higher PAH was significantly associated with worse inhibitory control (ß = -0.15, 95%CI: 0.29,-0.01 p = .03). Better inhibitory control was significantly associated with better reading comprehension (WJ-III Passage Comprehension, ß = 0.22, 95%CI: 0.09, 0.36, p < .002) and math skills (WJ-III Broad Math Index, ß = 0.32, 95%CI: 0.19, 0.45, p < .001), and trend level associations with better spelling skills (WJ-III Spelling, ß = 0.12, 95%CI: 0.02, 0.26, p = .10). Inhibitory control significantly mediated PAH-related achievement effects for Passage Comprehension (ß = -0.61, 95%CI: 1.49, -0.01) and Broad Math Index (ß = -1.09, 95%CI: 2.36, -0.03). CONCLUSIONS: Higher prenatal PAH exposure and lower childhood inhibitory control were associated with worse spelling, passage comprehension, and math in adolescence. Notably, childhood inhibitory control mediated PAH exposure-related effects on achievement in adolescents. Identifying these potential exposure-related phenotypes of learning problems may promote interventions that target inhibitory control deficits rather than content specific deficits.

Prenatal environmental tobacco smoke exposure alters children's cognitive control circuitry: A preliminary study.

BACKGROUND AND OBJECTIVES: Prenatal exposure to environmental tobacco smoke (ETS) is associated with increased attention problems in children, however, the effects of such exposure on children's brain structure and function have not been studied. Herein, we probed effects of prenatal ETS on children's cognitive control circuitry and behavior. METHODS: Forty-one children (7-9 years) recruited from a prospective longitudinal birth cohort of non-smoking mothers completed structural and task-functional magnetic resonance imaging to evaluate effects of maternal ETS exposure, measured by maternal prenatal urinary cotinine. Attention problems and externalizing behaviors were measured by parent report on the Child Behavior Checklist. RESULTS: Compared to non-exposed children, exposed children had smaller left and right thalamic and inferior frontal gyrus (IFG) volumes, with large effect sizes (p-FDR < .05, Cohen's D range from 0.79 to 1.07), and increased activation in IFG during the resolution of cognitive conflict measured with the Simon Spatial Incompatibility Task (38 voxels; peak t(25) = 5.25, p-FWE = .005). Reduced thalamic volume was associated with increased IFG activation and attention problems, reflecting poor cognitive control. Mediation analyses showed a trend toward left thalamic volume mediating the association between exposure and attention problems (p = .05). CONCLUSIONS: Our findings suggest that maternal ETS exposure during pregnancy has deleterious effects on the structure and function of cognitive control circuitry which in turn affects attentional capacity in school-age children. These findings are consistent with prior findings documenting the effects of active maternal smoking on chidlren's neurodevleoment, pointing to the neurotixicity of nicotine regardless of exposure pathway.

Contributions of Cerebellar White Matter Microstructure to Social Difficulty in Nonverbal Learning Disability.

Emerging evidence suggests that the cerebellum may contribute to variety of cognitive capacities, including social cognition. Nonverbal learning disability (NVLD) is characterized by visual-spatial and social impairment. Recent functional neuroimaging studies have shown that children with NVLD have altered cerebellar resting-state functional connectivity, which is associated with various symptom domains. However, little is known about cerebellar white matter microstructure in NVLD and whether it contributes to social deficits. Twenty-seven children (12 with NVLD, 15 typically developing (TD)) contributed useable diffusion tensor imaging data. Tract-based spatial statistics (TBSS) were used to quantify fractional anisotropy (FA) in the cerebellar peduncles. Parents completed the Child Behavior Checklist, providing a measure of social difficulty. Children with NVLD had greater fractional anisotropy in the left and right inferior cerebellar peduncle. Furthermore, right inferior cerebellar peduncle FA was associated with social impairment as measured by the Child Behavior Checklist Social Problems subscale. Finally, the association between NVLD diagnosis and greater social impairment was mediated by right inferior cerebellar peduncle FA. These findings provide additional evidence that the cerebellum contributes both to social cognition and to the pathophysiology of NVLD.

Dermatological services; patient profiling in a rural tertiary hospital.

BACKGROUND/OBJECTIVES: There is a paucity of research available regarding the epidemiology of patients attending dermatology outpatient services in Australia. Our objective was to analyse who was attending public dermatology outpatient clinics in a Northern Territory tertiary hospital, with a particular focus on Indigenous and rural patients. METHODS: This is a retrospective cohort study of patients who attended dermatology outpatient clinics between 1 January 2016 and 31 December 2016. Outcome measures included patient demographics (age, gender, ethnicity and postcode) and referrer details. RESULTS: Over the 12 month study period, 923 appointments were scheduled for 500 patients. Of the appointments scheduled, 667 were attended. Twelve per cent of patients were Indigenous, and of the total appointment attendances, 10% were by Indigenous patients. Of the 923 appointments, 28% were not attended, with a higher non-attendance rate for Indigenous patients at 36%. The majority of patients seen were adults, for both groups, but a larger proportion of Indigenous children were seen. Nine per cent of patients with a recorded address were from a remote region. CONCLUSION: Dermatology outpatient services are likely under-utilised by Indigenous, and remote patients. If we are to improve skin health in Australia, barriers such as limited access to dermatological services in remote regions must be addressed.

Altered structure and functional connectivity of the hippocampus are associated with social and mathematical difficulties in nonverbal learning disability.

The hippocampus is known to play a critical role in a variety of complex abilities, including visual-spatial reasoning, social functioning, and math. Nonverbal learning disability (NVLD) is a neurodevelopmental disorder characterized by deficits in visual-spatial reasoning that are accompanied by impairment in social function or mathematics, as well as motor or executive function skills. Despite the overlap between behaviors supported by the hippocampus and impairments in NVLD, the structure and function of the hippocampus in NVLD has not been studied. To address this gap in the literature, we first compared hippocampal volume and resting-state functional connectivity in children with NVLD (n = 24) and typically developing (TD) children (n = 20). We then explored associations between hippocampal structure, connectivity, and performance on measures of spatial, social, and mathematical ability. Relative to TD children, those with NVLD showed significant reductions in left hippocampal volume and greater hippocampal-cerebellar connectivity. In children with NVLD, reduced hippocampal volume associated with worse mathematical problem solving. Although children with NVLD exhibited more social problems (social responsiveness scale [SRS]) and higher hippocampal-cerebellar connectivity relative to TD children, greater connectivity was associated with fewer social problems among children with NVLD but not TD children. Such an effect may suggest a compensatory mechanism. These structural and functional alterations of the hippocampus may disrupt its putative role in organizing conceptual frameworks through cognitive mapping, thus contributing to the cross-domain difficulties that characterize NVLD.

Which types of conditions should be included in reproductive genetic carrier screening? Views of parents of children with a genetic condition.

Reproductive genetic carrier screening identifies couples with an increased chance of having children with autosomal and X-linked recessive conditions. Initially only offered for single conditions to people with a high priori risk, carrier screening is becoming increasingly offered to individuals/couples in the general population for a wider range of genetic conditions. Despite advances in genomic testing technology and greater availability of carrier screening panels, there is no consensus around which types of conditions to include in carrier screening panels. This study sought to identify which types of conditions parents of children with a genetic condition believe should be included in carrier screening. Participants (n = 150) were recruited through Royal Children's Hospital (RCH) Melbourne outpatient clinics, the Genetic Support Network of Victoria (GSNV) and a databank of children with hearing loss (VicCHILD). This study found that the majority of participants support offering carrier screening for: neuromuscular conditions (n = 128/134, 95.5%), early fatal neurodegenerative conditions (n = 130/141, 92.2%), chronic multi-system disorders (n = 124/135, 91.9%), conditions which cause intellectual disability (n = 128/139, 92.1%) and treatable metabolic conditions (n = 120/138, 87.0%). Views towards the inclusion of non-syndromic hearing loss (n = 88/135, 65.2%) and preventable adult-onset conditions (n = 75/135, 55.6%) were more mixed. Most participants indicated that they would use reproductive options to avoid having a child with the more clinically severe conditions, but most would not do so for clinically milder conditions. A recurring association was observed between participants' views towards carrier screening and their lived experience of having a child with a genetic condition.

Management of Dyslipidemia for Cardiovascular Disease Risk Reduction: Synopsis of the 2020 Updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.

DESCRIPTION: In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. METHODS: On 6 August to 9 August 2019, the VA/DoD Evidence-Based Practice Work Group (EBPWG) convened a joint VA/DoD guideline development effort that included clinical stakeholders and conformed to the Institute of Medicine's tenets for trustworthy clinical practice guidelines. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. RECOMMENDATIONS: This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.

Management of Dyslipidemia for cardiovascular disease risk Reduction: synopsis of the 2020 updated U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline

In June 2020, the U.S. Department of Veterans Affairs (VA) and U.S. Department of Defense (DoD) released a joint update of their clinical practice guideline for managing dyslipidemia to reduce cardiovascular disease risk in adults. This synopsis describes the major recommendations. The guideline panel developed key questions, systematically searched and evaluated the literature (English-language publications from 1 December 2013 to 16 May 2019), and developed 27 recommendations and a simple 1-page algorithm. The recommendations were graded by using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. This synopsis summarizes key features of the guideline in 7 crucial areas: targeting of statin dose (not low-density lipoprotein cholesterol goals), additional tests for risk prediction, primary and secondary prevention, laboratory testing, physical activity, and nutrition.

Complicated skin and soft tissue infections in remote indigenous communities.

The burden and consequences of skin infections for remote living indigenous people are high. While skin infections are recognised as an antecedent to conditions such as acute rheumatic fever in children, data are limited concerning skin infection complications such as cellulitis, abscesses and osteomyelitis in older children and adults. In a 1-year retrospective audit of 439 patients presenting to two remote health clinics, 330/439 (75%) patients presented with a skin infection and 18 (4%) developed a complication.