Elongin C (ELOC/TCEB1)-associated von Hippel-Lindau disease.

Around 95% of patients with clinical features that meet the diagnostic criteria for von Hippel-Lindau disease (VHL) have a detectable inactivating germline variant in VHL. The VHL protein (pVHL) functions as part of the E3 ubiquitin ligase complex comprising pVHL, elongin C, elongin B, cullin 2 and ring box 1 (VCB-CR complex), which plays a key role in oxygen sensing and degradation of hypoxia-inducible factors. To date, only variants in VHL have been shown to cause VHL disease. We undertook trio analysis by whole-exome sequencing in a proband with VHL disease but without a detectable VHL mutation. Molecular studies were also performed on paired DNA extracted from the proband's kidney tumour and blood and bioinformatics analysis of sporadic renal cell carcinoma (RCC) dataset was undertaken. A de novo pathogenic variant in ELOC NM_005648.4(ELOC):c.236A>G (p.Tyr79Cys) gene was identified in the proband. ELOC encodes elongin C, a key component [C] of the VCB-CR complex. The p.Tyr79Cys substitution is a mutational hotspot in sporadic VHL-competent RCC and has previously been shown to mimic the effects of pVHL deficiency on hypoxic signalling. Analysis of an RCC from the proband showed similar findings to that in somatically ELOC-mutated RCC (expression of hypoxia-responsive proteins, no somatic VHL variants and chromosome 8 loss). These findings are consistent with pathogenic ELOC variants being a novel cause for VHL disease and suggest that genetic testing for ELOC variants should be performed in individuals with suspected VHL disease with no detectable VHL variant.

Sex-specific associations between self-reported physical activity and PTSD among survivors of sexual violence.

This study examined sex-specific associations between sexual violence (SV) type and physical activity, and identified associations between PTSD symptoms and physical activity, all among cisgender men and women survivors of SV. Cross-sectional data from men (n = 197) and women (n = 356) survivors of SV were analyzed with stratified (men; women) hierarchical logistic regressions. Additionally, fully adjusted models for the total sample included interaction terms to further assess whether associations between SV type as well as PTSD symptoms (sum, clusters) and physical activity differed significantly by sex. Sexual assault was negatively associated with physical activity in the crude model among women (ORs: 0.58; p < 0.05). Harassment was positively associated with physical activity in the crude and adjusted models (ORs:1.92-2.16; ps<0.05) among women. Among men, there were no significant relationships. Regarding PTSD symptoms among women, crude and adjusted stratified models identified significant positive relationships with intrusion (ORs: 1.18-1.22; ps<0.05). Crude and adjusted models revealed significant positive relationships between avoidance and activity (ORs:1.38-1.41; ps<0.05) among men but not women. The interaction term for this difference in the association between avoidance and physical activity by sex was significant (OR: 0.65; 95%CI: 0.48-0.88; p < 0.01). Overall, findings provide evidence for sex-specific associations between SV and physical activity.

Barriers and Facilitators to Muscle-Strengthening Activity Among Latinas in the U.S.: Results From Formative Research Assessments.

BACKGROUND: Latinas are disproportionately affected by low physical activity (PA) levels and related health conditions (e.g., diabetes, obesity). Few Latinas in the U.S. (17%) meet the National PA Guidelines for both aerobic PA and muscle-strengthening activity (MSA), yet, research to date in this population has focused almost exclusively on aerobic PA. Performing regular MSA is linked with numerous health improvements and reduced mortality; thus, may be key to addressing health disparities in this community. This study examined perspectives on engaging in MSA among Latinas enrolled in two aerobic PA RCTs. METHODS: Brief quantitative surveys were conducted to assess interest in MSA among Latinas (N = 81), along with 19 follow-up in-depth semi-structured interviews on knowledge, barriers, and facilitators for engaging in regular MSA. Interview transcripts were analyzed by two independent bilingual researchers using a directed content analysis approach. RESULTS: Eighty-one Latinas (18-65 years) completed the survey. Most (91%) expressed interest in learning more about MSA and 60% reported not knowing how to do MSA as a substantial MSA barrier. Interview results indicated Latinas were aware of health benefits of MSA and motivated to engage in MSA but reported barriers (e.g., perception that MSA is for men, a taboo topic, and lack of knowledge on how to do MSA). CONCLUSION: This study contributes to a critical gap in PA research among Latinas. Findings will inform future culturally appropriate MSA interventions in this at-risk population. Addressing MSA and aerobic PA together in future interventions will provide a more comprehensive approach to reducing PA-related health disparities in Latinas than aerobic PA alone.

Exercise as Medicine for People with a Substance Use Disorder: An ACSM Call to Action Statement.

ABSTRACT: Over 20 million Americans are living with a substance use disorder (SUD) and nearly 100,000 die annually from drug overdoses, with a majority involving an opioid. Many people with SUD have co-occurring chronic pain and/or a mental health disorder. Exercise is a frontline treatment for chronic pain and is an effective strategy for reducing depression and anxiety and improving overall mental health. Several studies have shown that exercise improves SUD-related outcomes including abstinence; however, there is limited large-scale randomized clinical trial evidence to inform integration of exercise into practice. In this Call to Action, we aim to raise awareness of the specific issues that should be addressed to advance exercise as medicine in people with SUD including the challenges of co-occurring chronic pain, mental illness, and cardiopulmonary health conditions. In addition, specialized training for exercise professionals and other support staff should be provided on these issues, as well as on the multiple dimensions of stigma that can impair engagement in treatment and overall recovery in people with SUD.

Biological and psychological predictors of heart rate patterns during physical activity.

Objective: Latent class modeling (LCM) offers a promising approach for examining correlates of heart rate (HR) patterns over multiple exercise sessions. This research examined biological and psychological variables associated with different patterns of HR response to physical activity (PA). Methods: In a three-arm randomized controlled trial (exercise video games vs. standard exercise vs. non-exercise control), HR was recorded during PA sessions over a 12-week period. LCM identified three patterns of HR during PA across 189 participants in active arms: 1) high HR across sessions with low variability within sessions, 2) linear increase in HR across sessions with low variability within sessions, and 3) high variability in HR across all sessions. Associations with biological (resting heart rate, blood pressure, BMI, age, cholesterol, triglycerides, HbA1c) and psychological (depression, motivations for PA, PA-induced feelings) predictors of latent class membership were iteratively tested. Results: Psychological variables played as important a role in the final model as biological variables for predicting latent class membership. Few differences were found between LC1 and LC2, but LC3 differed from the other two groups in that participants were likelier to report that feel revitalized after PA (vs. LC1 and LC2), to be less motivated for PA (vs. LC1), reported greater depression (vs. LC1 and LC2), and were younger (vs. LC1). Conclusions: These findings demonstrate the potential of LCM to identify biological and psychological factors associated with chronotropic responses to PA, and advance understanding of the role of psychological factors in chronotropic PA outcomes.

Acute Psychological Effects of Resistance Exercise in Men With Symptoms of Muscle Dysmorphia: A Pilot Study.

ABSTRACT: SantaBarbara, NJ, Nosrat, S, Whitworth, JW, Ciccolo, JT. acute psychological effects of resistance exercise in men with symptoms of muscle dysmorphia: A pilot study. J Strength Cond Res 37(2): 277-283, 2023-This study tested the acute psychological effects of resistance exercise in men with symptoms of muscle dysmorphia. Twenty-one men completed 4 on-site sessions including a single session of moderate- (70% of 10 repetition maximum [RM]) and high- (100% of 10RM) intensity resistance exercise in a counter balanced order separated by at least 48 hours. State body image, perceived muscle size, exercise enjoyment, and ratings of perceived exertion (RPE) were assessed before, during, and after each session, and statistical significance was set a priori at p < 0.05. State body image significantly improve from pre to post during both sessions ( p < 0.01), with greater effect sizes seen for the high- ( d = 0.57) compared with the moderate- ( d = 0.39) intensity session. Perceived muscle size improved from pre to post during the high-intensity only ( p < 0.01, d = 0.66), and subjects enjoyed the high-intensity session significantly more than the moderate-intensity session ( p = 0.01), despite significantly higher RPE at each timepoint ( p < 0.01). Results contend with previous findings that show more positive psychological effects of moderate- compared with high-intensity resistance exercise. Education and client observation are essential to be aware of the potential for muscle dysmorphia. In instances where muscle dysmorphia is suspected, referral to qualified mental health professionals is recommended.

Evaluation of tumour surveillance protocols and outcomes in von Hippel-Lindau disease in a national health service.

BACKGROUND: Von Hippel-Lindau (VHL) disease is an inherited tumour predisposition syndrome and a paradigm for the importance of early diagnosis and surveillance. However, there is limited information on the "real world" management of VHL disease. METHODS: A national audit of VHL disease in the United Kingdom. RESULTS: VHL disease was managed mostly via specialist clinics coordinated through regional clinical genetics services (but frequently involving additional specialties). Over the study period, 19 genetic centres saw 842 individuals (393 males, 449 females) with a clinical and/or molecular diagnosis of VHL disease and 74 individuals (35 male, 39 female) with a prior risk of 50% (affected parent). All centres offered retinal, central nervous system and abdominal surveillance to affected individuals and at-risk relatives though surveillance details differed between centres (but complied with international recommendations). Renal lesions detected on the first surveillance scan were, on average, larger than those detected during subsequent scans and the larger the diameter at detection the greater the likelihood of early intervention. CONCLUSIONS: In a state-funded health care system individuals with a rare inherited cancer predisposition syndrome are generally able to access appropriate surveillance and patient management is improved compared to historical data. The "real world" data from this study will inform the future development of VHL management protocols.

Resistance training for Black men with depressive symptoms: a pilot randomized controlled trial to assess acceptability, feasibility, and preliminary efficacy.

BACKGROUND: Depression is under-recognized in Black men, who are less likely to seek or have access to psychiatric treatment. Resistance training (RT; i.e., weight lifting) can improve depressive symptoms and may be more acceptable to Black men, but its effects have not been examined for Black men with depressive symptoms. METHODS: Fifty Black men with depressive symptoms were randomized to either (a) 12 weeks of RT (coupled with Behavioral Activation techniques to promote adherence) or (b) an attention-control group (Health, Wellness, and Education; HWE). Both groups met twice/week for 12 weeks, and follow-up assessments were done at end-of-treatment (EOT) and 6 months after enrollment. Changes in physical activity and muscular strength were collected as a manipulation check. The primary outcome was interviewer assessed symptoms of depression using the Quick Inventory of Depression Symptomology (QIDS). Secondary outcomes included self-reported depressive symptoms, anxiety, and stress. The association between change in QIDS from baseline to EOT and concurrent changes in physical activity and muscular strength in the RT group were explored as an initial assessment of mechanism. Longitudinal mixed effects regression models with subject-specific intercepts were used to examine intervention effects. RESULTS: A sample with high rates of medical comorbidities (e.g., 44% HIV positive), substance use (e.g., 34% smoking), and negative social determinates of health (e.g., 50% unemployed) was enrolled. Recruitment, engagement, and retention data indicate that the intervention and design were feasible. The RT group showed greater gains in self-reported exercise (b = 270.94, SE = 105.69, p = .01) and muscular strength (b = 11.71, SE = 4.23, p = .01 for upper body and b = 4.24, SE = 2.02, p = .04 for lower body) than the HWE group. The RT group had greater reductions in QIDS scores at both EOT (b = -3.00, SE = 1.34, p = .01) and 6 months (b = -2.63, SE = 1.81, p = .04). The RT group showed a greater reduction in anxiety at EOT (b = -2.67, SE = 1.06, p = .02). Findings regarding self-reported depressive symptoms and stress were non-significant, but in the expected direction with effect sizes in the small to medium range. In the RT group, improvement on the QIDS between baseline and EOT was associated with concurrent improvements in physical activity (b = 21.03, SE = 11.16, p = .02) and muscular strength (b = 1.27, SE = .44, p = .03 for upper body and b = .75, SE = .14, p = .03 for lower body). CONCLUSIONS: Results suggest that RT is feasible and may be efficacious for reducing depressive symptoms among underserved urban Black men. TRIAL REGISTRATION: ClinicalTrial.gov #: NCT03107039 (Registered 11/04/2017).

Pathogenic germline variants in patients with features of hereditary renal cell carcinoma: Evidence for further locus heterogeneity.

Inherited renal cell carcinoma (RCC) is associated with multiple familial cancer syndromes but most individuals with features of non-syndromic inherited RCC do not harbor variants in the most commonly tested renal cancer predisposition genes (CPGs). We investigated whether undiagnosed cases might harbor mutations in CPGs that are not routinely tested for by testing 118 individuals with features suggestive of inherited RCC (family history of RCC, two or more primary RCC aged <60 years, or early onset RCC ≤46 years) for the presence of pathogenic variants in a large panel of CPGs. All individuals had been prescreened for pathogenic variants in the major RCC genes. We detected pathogenic or likely pathogenic (P/LP) variants of potential clinical relevance in 16.1% (19/118) of individuals, including P/LP variants in BRIP1 (n = 4), CHEK2 (n = 3), MITF (n = 1), and BRCA1 (n = 1). Though the power to detect rare variants was limited by sample size the frequency of truncating variants in BRIP1, 4/118, was significantly higher than in controls (P = 5.92E-03). These findings suggest that the application of genetic testing for larger inherited cancer gene panels in patients with indicators of a potential inherited RCC can increase the diagnostic yield for P/LP variants. However, the clinical utility of such a diagnostic strategy requires validation and further evaluation and in particular, confirmation of rarer RCC genotype-phenotype associations is required.

Comprehensive Cancer-Predisposition Gene Testing in an Adult Multiple Primary Tumor Series Shows a Broad Range of Deleterious Variants and Atypical Tumor Phenotypes.

Multiple primary tumors (MPTs) affect a substantial proportion of cancer survivors and can result from various causes, including inherited predisposition. Currently, germline genetic testing of MPT-affected individuals for variants in cancer-predisposition genes (CPGs) is mostly targeted by tumor type. We ascertained pre-assessed MPT individuals (with at least two primary tumors by age 60 years or at least three by 70 years) from genetics centers and performed whole-genome sequencing (WGS) on 460 individuals from 440 families. Despite previous negative genetic assessment and molecular investigations, pathogenic variants in moderate- and high-risk CPGs were detected in 67/440 (15.2%) probands. WGS detected variants that would not be (or were not) detected by targeted resequencing strategies, including low-frequency structural variants (6/440 [1.4%] probands). In most individuals with a germline variant assessed as pathogenic or likely pathogenic (P/LP), at least one of their tumor types was characteristic of variants in the relevant CPG. However, in 29 probands (42.2% of those with a P/LP variant), the tumor phenotype appeared discordant. The frequency of individuals with truncating or splice-site CPG variants and at least one discordant tumor type was significantly higher than in a control population (χ2 = 43.642; p ≤ 0.0001). 2/67 (3%) probands with P/LP variants had evidence of multiple inherited neoplasia allele syndrome (MINAS) with deleterious variants in two CPGs. Together with variant detection rates from a previous series of similarly ascertained MPT-affected individuals, the present results suggest that first-line comprehensive CPG analysis in an MPT cohort referred to clinical genetics services would detect a deleterious variant in about a third of individuals.

Early Adolescent Binge Drinking Increases Risk of Psychopathology in Post-9/11 Veterans and Mild Traumatic Brain Injury Exacerbates Symptom Severity.

AIMS: To demonstrate that early adolescent binge drinking (BD) increases the risk for and/or severity of psychopathology in post-9/11 Veterans and determine if mild traumatic brain injury (mTBI) modifies risk. METHODS: Post-9/11 Veterans (n = 375) were classified into two groups: 57 Veterans with a history of early adolescent BD (E-BD; age of onset <15) and 318 who did not BD until age 15 or older (late-BD or L-BD; age of onset ≥15). History of military mTBI and mental health disorders were also assessed following military service. RESULTS: Logistic regression and analysis of variance (ANOVA) analyses revealed that the E-BD's had significantly higher prevalence of alcohol use disorders (AUDs) and more severe symptoms of AUD, substance use disorder (SUD), depression and stress. Two-way ANOVAs showed that history of military mTBI was differentially associated with posttraumatic stress disorder (PTSD) incidence and severity among Veterans who had engaged in early adolescent BD. Specifically, Veterans with a history of both early adolescent BD and military mTBI were at greater risk for a PTSD diagnosis and had more severe symptoms of PTSD than those with only a history of adolescent BD. The greater PTSD symptom severity in the comorbid group was driven by hyperarousal symptoms. CONCLUSIONS: A history of BD during early adolescence is prevalent among Veterans and is related to higher risk for AUD and more severe AUD, SUD, mood and stress symptoms later in life. Veterans with early BD and military mTBI showed greater incidence and severity of PTSD, indicating that mTBI, a common comorbidity among post-9/11 Veterans, exacerbates risk.

Characterization of renal cell carcinoma-associated constitutional chromosome abnormalities by genome sequencing.

Constitutional translocations, typically involving chromosome 3, have been recognized as a rare cause of inherited predisposition to renal cell carcinoma (RCC) for four decades. However, knowledge of the molecular basis of this association is limited. We have characterized the breakpoints by genome sequencing (GS) of constitutional chromosome abnormalities in five individuals who presented with RCC. In one individual with constitutional t(10;17)(q11.21;p11.2), the translocation breakpoint disrupted two genes: the known renal tumor suppressor gene (TSG) FLCN (and clinical features of Birt-Hogg-Dubé syndrome were detected) and RASGEF1A. In four cases, the rearrangement breakpoints did not disrupt known inherited RCC genes. In the second case without chromosome 3 involvement, the translocation breakpoint in an individual with a constitutional t(2;17)(q21.1;q11.2) mapped 12 Kb upstream of NLK. Interestingly, NLK has been reported to interact indirectly with FBXW7 and a previously reported RCC-associated translocation breakpoint disrupted FBXW7. In two cases of constitutional chromosome 3 translocations, no candidate TSGs were identified in the vicinity of the breakpoints. However, in an individual with a constitutional chromosome 3 inversion, the 3p breakpoint disrupted the FHIT TSG (which has been reported previously to be disrupted in two apparently unrelated families with an RCC-associated t(3;8)(p14.2;q24.1). These findings (a) expand the range of constitutional chromosome rearrangements that may be associated with predisposition to RCC, (b) confirm that chromosome rearrangements not involving chromosome 3 can predispose to RCC, (c) suggest that a variety of molecular mechanisms are involved the pathogenesis of translocation-associated RCC, and (d) demonstrate the utility of GS for investigating such cases.

Feasibility of Resistance Exercise for Posttraumatic Stress and Anxiety Symptoms: A Randomized Controlled Pilot Study.

Emerging evidence suggests that exercise may beneficially affect posttraumatic stress symptoms (PTSS), but few randomized trials exist. Additionally, the effects of resistance exercise (i.e., weight lifting or strength training) on PTSS have not been thoroughly examined. This study aimed to explore the feasibility of a brief high-intensity resistance exercise intervention for PTSS and related issues, such as anxiety, sleep, alcohol use, and depression, in non-treatment-seeking adults who screened positive for posttraumatic stress disorder (PTSD) and anxiety. The sample included 30 non-treatment-seeking, urban-dwelling adults (M age = 29.10 years, SD = 7.38; 73.3% female) who screened positive for PTSD and anxiety and were randomly assigned to either a 3-week resistance exercise intervention or a time-matched contact control condition. The results suggest the intervention was feasible, with 80.0% (n = 24) of participants completing the study, 88.9% of the resistance exercise sessions attended, and no adverse effects reported. Additionally, resistance exercise had large beneficial effects on symptoms of avoidance, d = 1.26, 95% CI [0.39, 2.14]; and hyperarousal, d = 0.90, 95% CI [0.06, 1.74], relative to the control condition. Resistance exercise also produced large improvements concerning sleep quality, d = 1.31, 95% CI [0.41, 2.21], and hazardous alcohol use, d = 0.99, 95% CI [0.13, 1.86], compared to the control condition. Overall, the findings suggest that 3 weeks of high-intensity resistance exercise is a feasible intervention for PTSS reduction in non-treatment-seeking adults who screen positive for PTSD and anxiety; additional research is needed to verify these preliminary findings.

Acute Effects of Resistance-Exercise Intensity in Depressed Black/African Americans Living With HIV: A Randomized Pilot Study.

Depressive symptoms and fatigue are prevalent among people living with human immunodeficiency virus. Resistance exercise is known to stimulate a positive affective response. OBJECTIVE: To examine the acute psychological effects of resistance-exercise intensity among Black/African-American people living with human immunodeficiency virus and experiencing depressive symptoms. METHODS: A total of 42 participants were randomized into a moderate- (n = 21) or high-intensity (n = 21) group. Assessments were collected before exercise (PRE), at the midpoint (MID), immediately following (POST) exercise, and 15 (DELAY 15) and 30 (DELAY 30) min after. RESULTS: In the moderate-intensity group, affect improved PRE to POST, PRE to DELAY 15 and DELAY 30, and perceived distress decreased from PRE to all time points. In the high-intensity group, affect declined PRE to MID, and perceived distress decreased PRE to DELAY 15 and DELAY 30. Perceived activation increased PRE to MID, and POST in both groups (ps < .01). CONCLUSIONS: The moderate-intensity group compared with the high-intensity group is more effective at improving affect and energy and at reducing distress.

Service dog training programs for veterans with PTSD: results of a pilot controlled study.

Service dog programs are increasingly being explored as complementary or alternative interventions for military veterans with posttraumatic stress disorder (PTSD). This paper details the results of a control group, pre-and-post pilot investigation evaluating the use of a 14-week service dog training program for veterans in central Florida. Thirty veterans diagnosed with PTSD, 15 in the intervention group and 15 in the waitlist controlled group, completed all pretests and posttests measures, consisting of the 136-item Trauma Symptom Inventory-2 and the 36-item World Health Organization-Disability Assessment Schedule 2.0. Compared to demographically similar veterans in the control group, participants who completed the service dog training program demonstrated significant decreases in posttraumatic symptomatology, intra/interpersonal difficulties associated with psychological trauma, and in disabilities secondary to their PTSD. Study findings, in combination with results from two other recently published controlled investigations, provide evidence supporting the endorsement and use of service dog programs as helpful complementary or alternative treatment options for some veterans. Social work practitioners may want to consider referring their veteran clients with PTSD to qualified service dog programs for adjunctive support when they are having difficulty engaging with or benefiting from office-based traditional therapy approaches.

A Systematic Review of the Effects of Resistance Training on Body Image.

The purpose of this systematic review was to identify and appraise the literature that has specifically tested the independent effects of resistance training (i.e., weightlifting) on body image in adults. A comprehensive search of electronic databases PubMed, Scopus, PsycNET, and Web of Science for relevant studies published in peer-reviewed journals through December 2016 was conducted, and PRISMA guidelines were followed. Inclusion criteria were that a study had to be (a) written in English, (b) published in a peer-reviewed journal, (c) conducted an assessment of body image using a validated scale before and after a stand-alone resistance training intervention (i.e., not coupled with another mode of treatment), and (d) excluded participants younger than 18 years. Methodological quality was assessed using the Physiotherapy Evidence Database (PEDro) scale. A total of 7,324 studies were identified, and 11 were included in this review. The majority (8 of 11) of studies concluded that resistance training can significantly improve multiple dimensions of body image, including body satisfaction, appearance evaluation, and social physique anxiety; however, only 3 studies were considered high quality based on their PEDro score, and several methodological limitations exist. Overall, resistance training seems to have the potential to improve body image in adults, but future high-quality studies with more rigorous testing methods and study designs are needed.

Acute effects of resistance exercise on affect, arousal, and urge to drink in temporarily abstinent young adult hazardous drinkers.

BACKGROUND AND OBJECTIVE: Young adults frequently engage in hazardous alcohol consumption, and many meet the diagnostic criteria for an alcohol use disorder. The urge to drink is a defining symptom of alcohol dependence, and it is closely tied to and exacerbated by negative affect. This study examined the acute effect of resistance exercise on affect, arousal, and drinking urges in young adult (ages 21-40) hazardous drinkers. METHODS: On two separate occasions, 14 participants underwent an 18-hour alcohol abstinence before completing, in a counter-balanced manner, a 20-minute session of resistance exercise and a 20-minute video control. RESULTS: Significant improvements in affect (t = 2.07, p = .04) and arousal (t = 4.09, p < .01), but not urge to drink, were found with exercise. CONCLUSION: Single sessions of resistance exercise can positively alter affect and arousal during alcohol abstinence. SCIENTIFIC SIGNIFICANCE: Practical exercise interventions designed to alter affect and arousal could potentially alter drinking. (Am J Addict 2016;25:623-627).

Wilms tumour resulting from paternal transmission of a TRIM28 pathogenic variant-A first report.

Wilms tumour (nephroblastoma) is a renal embryonal tumour that is frequently caused by constitutional variants in a small range of cancer predisposition genes. TRIM28 has recently been identified as one such gene. Previously, observational data strongly suggested a parent of origin effect, whereby Wilms tumour only occurred following maternal inheritance of a pathogenic genetic variant. However, here we report a child with bilateral Wilms tumour who had inherited a pathogenic TRIM28 variant from their father. This finding suggests that genetic counselling for paternally inherited pathogenic variants in TRIM28 should include discussion of a potential risk of Wilms tumour.

Traumatic Brain Injury and Posttraumatic Stress Disorder Are Associated with Physical Health Burden among Post-9/11 Women Veterans.

Background: Little research focuses on physical health outcomes of traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD) among post-9/11 women veterans (WVs). This study examined lifetime TBI, current PTSD, and their associations with biomarkers of cardiometabolic health, sleep, pain, and functional disability among post-9/11 WVs. Methods: WVs (n = 90) from the Translational Research Center for TBI and Stress Disorders longitudinal cohort study were included in this study. Gold standard clinician administered interviews assessed lifetime TBI (Boston Assessment of TBI-Lifetime) and current PTSD symptoms (Clinician-Administered PTSD Scale-IV). Objective measures of health included waist-hip ratio (WHR) and fasted blood biomarker (high density lipoprotein [HDL], low density lipoprotein [LDL], blood glucose, triglycerides) levels. Self-reported surveys assessed sleep, pain, and functional disability. Results: Just under two-thirds (58.9%) of WVs experienced a lifetime TBI, and just over half (53.3%) of this sample had a current PTSD diagnosis at the time of testing. Lifetime TBI was significantly associated with higher WHR, triglycerides levels, and worse pain and sleep (ps = <0.01 to 0.02; ds = 0.01 to 1.12). Current PTSD was significantly associated with higher WHR, lower HDL, and worse pain and sleep (ps = <0.01 to 0.02; ds = 0.009 to 1.19). PTSD was significantly associated with lower total functioning and each of its subdomains (ßs = -0.58 to 0.63; ps = <0.001 to 0.02). Lifetime TBI was significantly associated with total functioning, mobility, and life/work (ßs = -0.20 to 0.30; ps = <0.01 to 0.02). Conclusions: These findings highlight the importance of screening for lifetime TBI and cardiovascular disease for WVs and support transdiagnostic treatment approaches targeting physical health outcomes.

Characteristics, aetiology and implications for management of multiple primary renal tumours: a systematic review.

In a subset of patients with renal tumours, multiple primary lesions may occur. Predisposition to multiple primary renal tumours (MPRT) is a well-recognised feature of some inherited renal cancer syndromes. The diagnosis of MPRT should therefore provoke a thorough assessment for clinical and genetic evidence of disorders associated with predisposition to renal tumourigenesis. To better define the clinical and genetic characteristics of MPRT, a systematic literature review was performed for publications up to 3 April 2024. A total of 7689 patients from 467 articles were identified with MPRT. Compared to all patients with renal cell carcinoma (RCC), patients with MPRT were more likely to be male (71.8% versus 63%) and have an earlier age at diagnosis (<46 years, 32.4% versus 19%). In 61.1% of cases MPRT were synchronous. The proportion of cases with similar histology and the proportion of cases with multiple papillary renal cell carcinoma (RCC) (16.1%) were higher than expected. In total, 14.9% of patients with MPRT had a family history of cancer or were diagnosed with a hereditary RCC associated syndrome with von Hippel-Lindau (VHL) disease being the most common one (69.7%), followed by Birt-Hogg-Dubé (BHD) syndrome (14.2%). Individuals with a known or likely genetic cause were, on average, younger (43.9 years versus 57.1 years). In rare cases intrarenal metastatic RCC can phenocopy MPRT. We review potential genetic causes of MPRT and their implications for management, suggest an approach to genetic testing for individuals presenting with MPRT and considerations in cases in which routine germline genetic testing does not provide a diagnosis.