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Mendelian and early-onset severe psychiatric phenotypes often involve genetic variants having a large effect, offering opportunities for genetic discoveries and early therapeutic interventions. Here, the index case is an 18-year-old boy, who at 14 years of age had a decline in cognitive functioning over the course of a year and subsequently presented with catatonia, auditory and visual hallucinations, paranoia, aggression, mood dysregulation, and disorganized thoughts. Exome sequencing revealed a stop-gain mutation in RCL1 (NM_005772.4:c.370 C > T, p.Gln124Ter), encoding an RNA 3′-terminal phosphate cyclase-like protein that is highly conserved across eukaryotic species. Subsequent investigations across two academic medical centers identified eleven additional cases of RCL1 copy number variations (CNVs) with varying neurodevelopmental or psychiatric phenotypes. These findings suggest that dosage variation of RCL1 contributes to a range of neurological and clinical phenotypes.

16p13.11 microduplication syndrome has a variable presentation and is characterized primarily by neurodevelopmental and physical phenotypes resulting from copy number variation at chromosome 16p13.11. Given its variability, there may be features that have not yet been reported. The goal of this study was to use a patient \"self-phenotyping\" survey to collect data directly from patients to further characterize the phenotypes of 16p13.11 microduplication syndrome. This study aimed to (1) discover self-identified phenotypes in 16p13.11 microduplication syndrome that have been underrepresented in the scientific literature and (2) demonstrate that self-phenotyping tools are valuable sources of data for the medical and scientific communities. As part of a large study to compare and evaluate patient self-phenotyping surveys, an online survey tool, Phenotypr, was developed for patients with rare disorders to self-report phenotypes. Participants with 16p13.11 microduplication syndrome were recruited through the Boston Children's Hospital 16p13.11 Registry. Either the caregiver, parent, or legal guardian of an affected child or the affected person (if aged 18 years or above) completed the survey. Results were securely transferred to a Research Electronic Data Capture database and aggregated for analysis. A total of 19 participants enrolled in the study. Notably, among the 19 participants, aggression and anxiety were mentioned by 3 (16%) and 4 (21%) participants, respectively, which is an increase over the numbers in previously published literature. Additionally, among the 19 participants, 3 (16%) had asthma and 2 (11%) had other immunological disorders, both of which have not been previously described in the syndrome. Several phenotypes might be underrepresented in the previous 16p13.11 microduplication literature, and new possible phenotypes have been identified. Whenever possible, patients should continue to be referenced as a source of complete phenotyping data on their condition. Self-phenotyping may lead to a better understanding of the prevalence of phenotypes in genetic disorders and may identify previously unreported phenotypes.

Objectives To characterize practice patterns and outcomes in the management of low‐ and intermediate‐grade salivary gland carcinoma prior to the existence of treatment guidelines. Methods Analysis of a registry of patients who underwent parotid and submandibular gland resections for low‐and intermediate‐grade carcinomas between 2010 and 2019. Results Of all 786 patients included in the study, 726 (92%) had preoperative imaging and 653 (83%) had preoperative biopsy. Of the 729 patients with parotid gland cancer, the majority underwent superficial (n = 384, 53%) or total (n = 254, 35%) parotidectomy. In patients with facial nerve preservation, total parotidectomy was associated with a significant increase in transient facial weakness (72/177 (41%) vs. 82/311 (26%), RR 0.65, 95% CI 0.50–0.84, p < 0.05) and permanent facial nerve weakness (23/176 (13%) vs. 16/301 (5%), RR 0.41, 95% CI 0.22–0.75, p < 0.05) compared to superficial parotidectomy. Adjuvant radiation therapy (RT) was delivered to 285 (36%) patients. The proportion of patients receiving adjuvant RT declined significantly over the time period from 2015 to 2019 compared to 2010 to 2014 at 162/504 (32%) and 123/282 (44%), respectively (RR 0.74, 95% CI 0.61–0.89, p < 0.05). When comparing the time periods from 2015 to 2019 and 2010 to 2014, there was no significant difference in local control rates (RR 0.52, 95% CI 0.26–1.04, p = 0.06) or regional control rates (RR 0.75, 95% CI 0.26–2.13, p = 0.58). Conclusions Management of low‐ and intermediate‐grade salivary cancer from 2010 to 2019 was variable, which is expected given the rarity and heterogeneity of the disease and the lack of treatment guidelines prior to 2021. Most patients with parotid malignancies underwent superficial or total parotidectomy. The extent of parotidectomy had an impact on facial nerve function outcomes. Delivery of adjuvant radiation trended down with time. The data presented here will support dissemination of the guidelines and provide data that could inform future trials. Level of Evidence 2b.

Quantifying the effect of public health actions on population health is essential when justifying sustained public health investment. Using modeling, we conservatively estimated that rapid response to a multistate foodborne outbreak of Salmonella Typhimurium in the United States in 2018 potentially averted 94 reported cases and $633,181 in medical costs and productivity losses.

Aboriginal and Torres Strait Islander people who inject drugs face persistent health inequities, highlighting the need for programs that meet the needs of these groups. This study explored how intersectional stigma and discrimination affect Aboriginal and Torres Strait Islander people’s access to quality healthcare. Aboriginal and Torres Strait Islander participants aged ≥18 years who had injected drugs within the past 12 months were recruited from two regional needle and syringe programs (NSPs) and a major city NSP in Queensland, Australia. Participants completed a structured survey and yarned with an Aboriginal researcher and non-Indigenous research assistant about their healthcare experiences. Through a process of reflexive and thematic analysis, three major qualitative themes emerged: participants’ social circumstances and mental health challenges made help-seeking difficult and complex; enacted stigma and racism diminished access to health services and the quality of care received; and injecting drug use was associated with disconnection from culture and community. Privileging the expertise and voices of those with lived/living experience is essential for the creation of culturally safe, inclusive, and destigmatising healthcare services for Aboriginal and Torres Strait Islander people who inject drugs.

Background Dietary fish oil (DFO) has been identified as a micronutrient supplement with the potential to improve musculoskeletal health in old age. Few data are available for effects of DFO on muscle contractility, despite the significant negative impact of muscle weakness on age-related health outcomes. Accordingly, the effects of a DFO intervention on the contractile function and proteomic profile of adult and aged in an animal model of aging were investigated. Methods This preliminary study evaluated 14 adult (8 months) and 12 aged (22 months) male, Sprague-Dawley rats consuming a DFO-supplemented diet or a control diet for 8 weeks (7 adult and 6 aged/dietary group). Animal weight, food intake and grip strength were assessed at the start and end of the FO intervention. In situ force and contractile properties were measured in the medial gastrocnemius muscle following the intervention and muscles were processed for 2-D gel electrophoresis and proteomic analysis via liquid chromatography with tandem mass spectrometry, confirmed by immunoblotting. Effects of age, diet and age x diet interaction were evaluated by 2-way ANOVA. Results A significant ( P  = 0.022) main effect for DFO to increase (~ 15%) muscle contractile force was observed, without changes in muscle mass. Proteomic analysis revealed a small number of proteins that differed across age and dietary groups at least 2-fold, most of which related to metabolism and oxidative stress. In seven of these proteins (creatine kinase, triosephosphate isomerase, pyruvate kinase, parvalbumin, beta-enolase, NADH dehydrogenase and Parkin7/DJ1), immunoblotting corroborated these findings. Parvalbumin showed only an effect of diet (increased with DFO) ( P  = 0.003). Significant age x diet interactions were observed in the other proteins, generally demonstrating increased expression in adult and decreased expression aged rats consuming DFO (all P  > 0.011). However, correlational analyses revealed no significant associations between contractile parameters and protein abundances. Conclusions Results of this preliminary study support the hypothesis that DFO can enhance musculoskeletal health in adult and aged muscles, given the observed improvement in contractile function. The fish oil supplement also alters protein expression in an age-specific manner, but the relationship between proteomic and contractile responses remains unclear. Further investigation to better understand the magnitude and mechanisms muscular effects of DFO in aged populations is warranted.

Background Indigenous Australians diagnosed with cancer have poorer survival compared to non-Indigenous Australians. We aim to: 1) identify differences by Indigenous status in out-of-pocket expenditure for the first three-years post-diagnosis; 2) identify differences in the quantity and cost of healthcare services accessed; and 3) estimate the number of additional services required if access was equal between Indigenous and non-Indigenous people with cancer. Methods We used CancerCostMod, a model using linked administrative data. The base population was all persons diagnosed with cancer in Queensland, Australia (01JUL2011 to 30JUN2012) ( n  = 25,553). Each individual record was then linked to their Admitted Patient Data Collection, Emergency Data Information System, Medicare Benefits Schedule (MBS), and Pharmaceutical Benefits Scheme (PBS) records (01JUL2011 to 30JUN2015). We then weighted the population to be representative of the Australian population (approximately 123,900 Australians, 1.7% Indigenous Australians). The patient co-payment charged for each MBS service and PBS prescription was summed for each month from date of diagnosis to 36-months post-diagnosis. We then limited our model to MBS items to identify the quantity and type of healthcare services accessed during the first three-years. Results On average Indigenous people with cancer had less than half the out-of-pocket expenditure for each 12-month period (0–12 months: mean $401 Indigenous vs $1074 non-Indigenous; 13–24 months: mean $200 vs $484; and 25–36 months: mean $181 vs $441). A stepwise generalised linear model of out-of-pocket expenditure found that Indigenous status was a significant predictor of out of pocket expenditure. We found that Indigenous people with cancer on average accessed 236 services per person, however, this would increase to 309 services per person if Indigenous people had the same rate of service use as non-Indigenous people. Conclusions Indigenous people with cancer had lower out-of-pocket expenditure, but also accessed fewer Medicare services compared to their non-Indigenous counterparts. Indigenous people with cancer were less likely to access specialist attendances, pathology tests, and diagnostic imaging through MBS, and more likely to access primary health care, such as services provided by general practitioners.

Background: Rotator cuff repair is one of the most common surgical procedures performed on the shoulder. Previous studies have indicated that pain and disability can vary significantly between patients with similarly appearing rotator cuff tears on diagnostic imaging. Prior literature has compared functional outcomes between operative and nonoperative treatments as well as variability in surgical techniques. However, few studies have examined postoperative outcomes based on patient factors such as sex. Purpose: To compare patient-reported outcomes after rotator cuff repair between men and women. Study Design: Cohort study; Level of evidence, 2. Methods: A total of 283 patients (153 male, 130 female) who underwent primary arthroscopic rotator cuff repair were included in this study; of those, 275 patients (97.2%) completed 1-year follow-up. Patient-reported pain visual analog scale (VAS), Veterans RAND 12-item Health Survey (VR-12 mental and physical components), American Shoulder and Elbow Surgeons (ASES), and Single Assessment Numeric Evaluation (SANE) scores were collected preoperatively and at 2 weeks, 6 weeks, 3 months, 6 months, and 1 year postoperatively using an electronic outcomes system. Results: Women reported higher VAS pain scores when compared with men preoperatively (P < .01) and at 2 weeks (P < .01), 6 weeks (P < .01), and 3 months (P = .02) postoperatively. Additionally, women experienced a greater overall change in the mean VAS score preoperatively when compared with 1 year postoperatively (P < .01). The use of narcotic pain medication 2 weeks after surgery was greater in women (P = .032). Women had significantly lower preoperative VR-12 mental scores (P = .03) and experienced a greater increase in the mean VR-12 mental score preoperatively when compared with 1 year postoperatively (P < .01). Men had higher ASES scores preoperatively (P < .01) and at 3 months postoperatively (P < .01). Women experienced a greater overall change in the ASES score preoperatively when compared with 1 year postoperatively (P < .01). Conclusion: Women reported greater pain and decreased shoulder function compared with men during the initial 3 months after arthroscopic rotator cuff repair. There were no sex-based differences in patient-reported outcomes at 1-year follow-up. The results of this study indicate that there are sex-related differences in the early postoperative recovery of patients undergoing rotator cuff repair, contributing to postoperative expectations for both clinicians and patients alike.

The purpose of this study was to determine the efficacy of nonopioid pain management following arthroscopic partial meniscectomy and/or chondroplasty and to assess patients' attitudes regarding their need for opioid pain medication following these procedures. Patients who underwent a knee arthroscopy procedure for either partial meniscectomy and/or chondroplasty from July 2016 to January 2017 by a single surgeon at a single institution were included. Medical records were reviewed, and demographics were recorded. Two weeks postoperatively, patients self-reported opioid and nonopioid medication use. Patients were also questioned regarding their perceived need for opioid medication, whether they felt their pain was adequately controlled, and how their pain compared with their preoperative expectations. Thirty-four patients (17 male, 17 female), with a mean age at the time of surgery of 47.79 years (range, 19–68 years), were included. Eighty-two percent (n=28) of the patients reported using nonopioid analgesics for pain control, whereas 18% (n=6) reported using opioids. Of those not using opioids, 96.4% (n=27) reported not feeling the need for opioid medications. Three of 6 patients requiring opioids were unable to take nonsteroidal anti-inflammatory drugs. All 6 patients who took opioids felt that they needed them for adequate pain control. This study provides initial encouragement that it is largely possible to remove opioids from the postoperative pain regimen of knee arthroscopy patients and maintain adequate pain control and patient satisfaction. [ Orthopedics . 2018; 41(4):209–214.]

ABSTRACTObjectivesIndigenous Australians experience higher levels of psychological distress compared to the general population. Physical activity is a culturally acceptable approach, associated with reduction of depressive symptoms. The protective properties of physical activity for depressive symptoms are yet to be evaluated in older Indigenous Australians. DesignA two-phase study design comprised of a qualitative thematic analysis following a quantitative regression and moderation analysis. ParticipantsFirstly, a total of 336 Indigenous Australians aged 60 years and over from five NSW areas participated in assessments on mental health, physical activity participation, and childhood trauma. Secondly, a focus group of seven Indigenous Australians was conducted to evaluate barriers and facilitators to physical activity. MeasurementsRegression and moderation analyses examined links between depression, childhood trauma, and physical activity. Thematic analysis was conducted exploring facilitators and barriers to physical activity following the focus group. ResultsChildhood trauma severity and intensity of physical activity predicted depressive symptoms. Physical activity did not affect the strength of the relationship between childhood trauma and depression. Family support and low impact activities facilitated commitment to physical activity. In contrast, poor mental health, trauma, and illness acted as barriers. ConclusionPhysical activity is an appropriate approach for reducing depressive symptoms and integral in maintaining health and quality of life. While situational factors, health problems and trauma impact physical activity, accessing low-impact group activities with social support was identified to help navigate these barriers.