Search

© 2015 Halladay et al.One of the most consistent findings in autism spectrum disorder (ASD) research is a higher rate of ASD diagnosis in males than females. Despite this, remarkably little research has focused on the reasons for this disparity. Better und

We analyzed predictors of parent-reported initial diagnosis (autistic disorder [AD], pervasive developmental disorder-not otherwise specified [PDD-NOS], pervasive developmental disorder ['PDD'] and autism spectrum disorder ['ASD'], and Asperger syndrome [AS]), among 6,176 individuals with autism spectrum disorders diagnosed from 1994 through 2007. Overall, distribution of diagnoses was influenced by a secular time trend factor; other significant factors included ethnicity, white race, geographic location, urbanicity, and initial evaluator. Since 2001, most initial diagnoses of AD and AS have remained steady while 'PDD' and PDD-NOS have decreased. 'ASD' diagnoses have increased, especially among school-based teams; AS diagnoses also increased uniquely among these evaluators. Findings from this study suggest that current diagnostic guidelines may not be meeting all community evaluator needs. [ABSTRACT FROM AUTHOR]

Trypanosomatids are single-celled parasites responsible for human and animal disease. Typically, colonization of an insect host is required for transmission. Stable attachment of parasites to insect tissues via their single flagellum coincides with differentiation and morphological changes. Although attachment is a conserved stage in trypanosomatid life cycles, the molecular mechanisms are not well understood. To study this process, we elaborate upon an in vitro model in which the swimming form of the trypanosomatid Crithidia fasciculata rapidly differentiates following adhesion to artificial substrates. Live imaging of cells transitioning from swimming to attached shows parasites undergoing a defined sequence of events, including an initial adhesion near the base of the flagellum immediately followed by flagellar shortening, cell rounding, and the formation of a hemidesmosome-like attachment plaque between the tip of the shortened flagellum and the substrate. Quantitative proteomics of swimming versus attached parasites suggests differential regulation of cyclic adenosine monophosphate (cAMP)-based signaling proteins. We have localized two of these proteins to the flagellum of swimming C. fasciculata ; however, both are absent from the shortened flagellum of attached cells. Pharmacological inhibition of cAMP phosphodiesterases increased cAMP levels in the cell and prevented attachment. Further, treatment with inhibitor did not affect the growth rate of either swimming or established attached cells, indicating that its effect is limited to a critical window during the early stages of adhesion. These data suggest that cAMP signaling is required for attachment of C. fasciculata and that flagellar signaling domains may be reorganized during differentiation and attachment.IMPORTANCETrypanosomatid parasites cause significant disease burden worldwide and require insect vectors for transmission. In the insect, parasites attach to tissues, sometimes dividing as attached cells or producing motile, infectious forms. The significance and cellular mechanisms of attachment are relatively unexplored. Here, we exploit a model trypanosomatid that attaches robustly to artificial surfaces to better understand this process. This attachment recapitulates that observed in vivo and can be used to define the stages and morphological features of attachment as well as conditions that impact attachment efficiency. We have identified proteins that are enriched in either swimming or attached parasites, supporting a role for the cyclic AMP signaling pathway in the transition from swimming to attached. As this pathway has already been implicated in environmental sensing and developmental transitions in trypanosomatids, our data provide new insights into activities required for parasite survival in their insect hosts., Competing Interests: The authors declare no conflict of interest.

The continued emergence of antimalarial drug resistance highlights the need to develop new antimalarial therapies. Unfortunately, new drug development is often hampered by poor drug-like properties of lead compounds. Prodrugging temporarily masks undesirable compound features, improving bioavailability and target penetration. We have found that lipophilic diester prodrugs of phosphonic acid antibiotics, such as fosmidomycin, exhibit significantly higher antimalarial potency than their parent compounds (1). However, the activating enzymes for these prodrugs were unknown. Here, we show that an erythrocyte enzyme, acylpeptide hydrolase (APEH) is the major activating enzyme of multiple lipophilic ester prodrugs. Surprisingly, this enzyme is taken up by the malaria parasite, Plasmodium falciparum , where it localizes to the parasite cytoplasm and retains enzymatic activity. Using a novel fluorogenic ester library, we characterize the structure activity relationship of APEH, and compare it to that of P. falciparum esterases. We show that parasite-internalized APEH plays an important role in the activation of substrates with branching at the alpha carbon, in keeping with its exopeptidase activity. Our findings highlight a novel mechanism for antimicrobial prodrug activation, relying on a host-derived enzyme to yield activation at a microbial target. Mutations in prodrug activating enzymes are a common mechanism for antimicrobial drug resistance (2-4). Leveraging an internalized host enzyme would circumvent this, enabling the design of prodrugs with higher barriers to drug resistance.

The parasite Cryptosporidium is a leading agent of diarrhoeal disease in young children, and a cause and consequence of chronic malnutrition 1,2 . There are no vaccines and only limited treatment options 3 . The parasite infects enterocytes, in which it engages in asexual and sexual replication 4 , both of which are essential to continued infection and transmission. However, their molecular mechanisms remain largely unclear 5 . Here we use single-cell RNA sequencing to reveal the gene expression programme of the entire Cryptosporidium parvum life cycle in culture and in infected animals. Diverging from the prevailing model 6 , we find support for only three intracellular stages: asexual type-I meronts, male gamonts and female gametes. We reveal a highly organized program for the assembly of components at each stage. Dissecting the underlying regulatory network, we identify the transcription factor Myb-M as the earliest determinant of male fate, in an organism that lacks genetic sex determination. Conditional expression of this factor overrides the developmental program and induces widespread maleness, while conditional deletion ablates male development. Both have a profound impact on the infection. A large set of stage-specific genes now provides the opportunity to understand, engineer and disrupt parasite sex and life cycle progression to advance the development of vaccines and treatments., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)

Background: SPARK launched in 2016 to build a US cohort of autistic individuals and their family members. Enrollment includes online consent to share data and optional consent to provide saliva for genomic analysis. SPARK's recruitment strategies include social media and support of a nation-wide network of clinical sites. This study evaluates SPARK's recruitment strategies to enroll a core study population., Methods: Individuals who joined between January 31, 2018, and May 29, 2019 were included in the analysis. Data include sociodemographic characteristics, clinical site referral, the website URL used to join, how the participant heard about SPARK, enrollment completion (online registration, study consents, and returning saliva sample), and completion of the baseline questionnaire. Logistic regressions were performed to evaluate the odds of core participant status (completing enrollment and baseline questionnaire) by recruitment strategy., Results: In total, 31,715 individuals joined during the study period, including 40% through a clinical site. Overall, 88% completed online registration, 46% returned saliva, and 38% were core participants. Those referred by a clinical site were almost twice as likely to be core participants. Those who directly visited the SPARK website or performed a Google search were more likely to be core participants than those who joined through social media., Discussion: Being a core participant may be associated with the "personal" connection and support provided by a clinical site and/or site staff, as well as greater motivation to seek research opportunities. Findings from this study underscore the value of adopting a multimodal recruitment approach that combines social media and a physical presence., Competing Interests: The authors have no conflicts of interest to declare., (© The Author(s) 2023.)

Port sediments are often contaminated with metals and organic compounds from anthropogenic sources. Remobilization of sediment during a planned expansion of Port Everglades near Fort Lauderdale, Florida (USA) has the potential to harm adjacent benthic communities, including coral reefs. Twelve sediment cores were collected from four Port Everglades sites and a control site; surface sediment was collected at two nearby coral reef sites. Sediment cores, sampled every 5 cm, were analyzed for 14 heavy metals using inductively coupled plasma-mass spectrometry. Results for all three locations yielded concentration ranges (µg/g): As (0.607-223), Cd (n/d-0.916), Cr (0.155-56.8), Co (0.0238-7.40), Cu (0.004-215), Pb (0.0169-73.8), Mn (1.61-204), Hg (n/d-0.736), Mn (1.61-204), Ni (0.232-29.3), Se (n/d-4.79), Sn (n/d-140), V (0.160-176), and Zn (0.112-603), where n/d = non-detected. The geo-accumulation index shows moderate-to-strong contamination of As and Mo in port sediments, and potential ecological risk indicates moderate-to-significantly high overall metal contamination. All four port sites have sediment core subsamples with As concentrations above both threshold effect level (TEL, 7.24 µg/g) and probable effect level (PEL, 41.6 µg/g), while Mo geometric mean concentrations exceed the background continental crust level (1.5 µg/g) threshold. Control site sediments exceed TEL for As, while the reef sites has low to no overall heavy metal contamination. Results of this study indicate there is a moderate to high overall ecological risk from remobilized sediment due to metal contamination. Due to an imminent dredging at Port Everglades, this could have the potential to harm the threatened adjacent coral communities and surrounding protected habitats., Competing Interests: The authors declare there are no competing interests., (©2023 Giarikos et al.)

Background: Conventional radiographs and clinical reassessment are considered guides in managing clinically suspected scaphoid fractures. This is a unique study as it assessed the value of conventional radiographs and clinical reassessment in a cohort of patients, all of whom underwent additional imaging, regardless of the outcome of conventional radiographs and clinical reassessment., Questions/purposes: (1) What is the diagnostic performance of conventional radiographs in patients with a clinically suspected scaphoid fracture compared with high-resolution peripheral quantitative CT (HR-pQCT)? (2) What is the diagnostic performance of clinical reassessment in patients with a clinically suspected scaphoid fracture compared with HR-pQCT? (3) What is the diagnostic performance of conventional radiographs and clinical reassessment combined compared with HR-pQCT?, Methods: Between December 2017 and October 2018, 162 patients with a clinically suspected scaphoid fracture presented to the emergency department (ED). Forty-six patients were excluded and another 25 were not willing or able to participate, which resulted in 91 included patients. All patients underwent conventional radiography in the ED and clinical reassessment 7 to 14 days later, together with CT and HR-pQCT. The diagnostic performance characteristics and accuracy of conventional radiographs and clinical reassessment were compared with those of HR-pQCT for the diagnosis of fractures since this was proven to be superior to CT scaphoid fracture detection. The cohort included 45 men and 46 women with a median (IQR) age of 52 years (29 to 67). Twenty-four patients with a median age of 44 years (35 to 65) were diagnosed with a scaphoid fracture on HR-pQCT., Results: When compared with HR-pQCT, conventional radiographs alone had a sensitivity of 67% (95% CI 45% to 84%), specificity of 85% (95% CI 74% to 93%), positive predictive value (PPV) of 62% (95% CI 46% to 75%), negative predictive value (NPV) of 88% (95% CI 80% to 93%), and a positive and negative likelihood ratio (LR) of 4.5 (95% CI 2.4 to 8.5) and 0.4 (95% CI 0.2 to 0.7), respectively. Compared with HR-pQCT, clinical reassessment alone resulted in a sensitivity of 58% (95% CI 37% to 78%), specificity of 42% (95% CI 30% to 54%), PPV of 26% (95% CI 19% to 35%), NPV of 74% (95% CI 62% to 83%), as well as a positive and negative LR of 1.0 (95% CI 0.7 to 1.5) and 1.0 (95% CI 0.6 to 1.7), respectively. Combining clinical examination with conventional radiography produced a sensitivity of 50% (95% CI 29% to 71%), specificity of 91% (95% CI 82% to 97%), PPV of 67% (95% CI 46% to 83%), NPV of 84% (95% CI 77% to 88%), as well as a positive and negative LR of 5.6 (95% CI 2.4 to 13.2) and 0.6 (95% CI 0.4 to 0.8), respectively., Conclusion: The accuracy of conventional radiographs (80% compared with HR-pQCT) and clinical reassessment (46% compared with HR-pQCT) indicate that the value of clinical reassessment is limited in diagnosing scaphoid fractures and cannot be considered directive in managing scaphoid fractures. The combination of conventional radiographs and clinical reassessment does not increase the accuracy of these diagnostic tests compared with the accuracy of conventional radiographs alone and is therefore also limited in diagnosing scaphoid fractures., Level of Evidence: Level II, diagnostic study., Competing Interests: All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed on request., (Copyright © 2022 by the Association of Bone and Joint Surgeons.)

Improving the clinical outcome of scaphoid fractures may benefit from adequate monitoring of their healing in order to for example identify complications such as scaphoid nonunion at an early stage and to adjust the treatment strategy accordingly. However, quantitative assessment of the healing process is limited with current imaging modalities. In this study, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used for the first time to assess the changes in bone density, microarchitecture, and strength during the healing of conservatively-treated scaphoid fractures. Thirteen patients with a scaphoid fracture (all confirmed on HR-pQCT and eleven on CT) received an HR-pQCT scan at baseline and three, six, twelve, and 26 weeks after first presentation at the emergency department. Bone mineral density (BMD) and trabecular microarchitecture of the scaphoid bone were quantified, and failure load (FL) was estimated using micro-finite element analysis. Longitudinal changes were evaluated with linear mixed-effects models. Data of two patients were excluded due to surgical intervention after the twelve-week follow-up visit. In the eleven fully evaluable patients, the fracture line became more apparent at 3 weeks. At 6 weeks, individual trabeculae at the fracture region became more difficult to identify and distinguish from neighboring trabeculae, and this phenomenon concerned a larger region around the fracture line at 12 weeks. Quantitative assessment showed that BMD and FL were significantly lower than baseline at all follow-up visits with the largest change from baseline at 6 weeks (-13.6% and - 23.7%, respectively). BMD remained unchanged thereafter, while FL increased. Trabecular thickness decreased significantly from baseline at three (-3.9%), six (-6.7%), and twelve (-4.4%) weeks and trabecular number at six (-4.5%), twelve (-7.3%), and 26 (-7.9%) weeks. Trabecular separation was significantly higher than baseline at six (+13.3%), twelve (+19.7%), and 26 (+16.3%) weeks. To conclude, this explorative HR-pQCT study showed a substantial decrease in scaphoid BMD, Tb.Th, and FL during the first 6 weeks of healing of conservatively-treated scaphoid fractures, followed by stabilization or increase in these parameters. At 26 weeks, BMD, trabecular microarchitecture, and FL were not returned to baseline values., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)

Scaphoid fractures are difficult to diagnose with current imaging modalities. It is unknown whether the shape of the scaphoid bone, assessed by statistical shape modeling, can be used to differentiate between fractured and non-fractured bones. Therefore, the aim of this study was to investigate whether the presence of a scaphoid fracture is associated with shape modes of a statistical shape model (SSM). Forty-one high-resolution peripheral quantitative computed tomography (HR-pQCT) scans were available from patients with a clinically suspected scaphoid fracture of whom 15 patients had a scaphoid fracture. The scans showed no motion artefacts affecting bone shape. The scaphoid bones were semi-automatically contoured, and the contours were converted to triangular meshes. The meshes were registered, followed by principal component analysis to determine mean shape and shape modes describing shape variance. The first five out of the forty shape modes cumulatively explained 87.8% of the shape variance. Logistic regression analysis was used to study the association between shape modes and fracture presence. The regression models were used to classify the 41 scaphoid bones as fractured or non-fractured using a cut-off value that maximized the sum of sensitivity and specificity. The classification of the models was compared with fracture diagnosis on HR-pQCT. A regression model with four shape modes had an area under the ROC-curve of 72.3% and correctly classified 75.6% of the scaphoid bones (fractured: 60.0%, non-fractured: 84.6%). To conclude, fracture presence in patients with a clinically suspected scaphoid fracture appears to be associated with the shape of the scaphoid bone., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Introduction: The aim of this study was to investigate the associations of patient characteristics, bone mineral density (BMD), bone microarchitecture and calculated bone strength with secondary displacement of a DRF based on radiographic alignment parameters., Materials and Methods: Dorsal angulation, radial inclination and ulnar variance were assessed on conventional radiographs of a cohort of 251 patients, 38 men and 213 women, to determine the anatomic position of the DRF at presentation (primary position) and during follow-up. Secondary fracture displacement was assessed in the non-operatively treated patients (N = 154) with an acceptable position, preceded (N = 97) or not preceded (N = 57) by primary reduction (baseline position). Additionally, bone microarchitecture and calculated bone strength at the contralateral distal radius and tibia were assessed by HR-pQCT in a subset of, respectively, 63 and 71 patients., Outcome: Characteristics of patients with and without secondary fracture displacement did not differ. In the model with adjustment for primary reduction [OR 22.00 (2.27-212.86), p = 0.008], total [OR 0.16 (95% CI 0.04-0.68), p = 0.013] and cortical [OR 0.19 (95% CI 0.05-0.80], p = 0.024] volumetric BMD (vBMD) and cortical thickness [OR 0.13 (95% CI 0.02-0.74), p = 0.021] at the distal radius were associated with secondary DRF displacement. No associations were found for other patient characteristics, such as age gender, BMD or prevalent vertebral fractures., Conclusions: In conclusion, our study indicates that besides primary reduction, cortical bone quality may be important for the risk of secondary displacement of DRFs., (© 2020. The Author(s).)

The impact of the 2019 coronavirus pandemic (COVID-19) in the United States is unprecedented, with unknown implications for the autism community. We surveyed 3502 parents/caregivers of individuals with an autism spectrum disorder (ASD) enrolled in Simons Powering Autism Research for Knowledge (SPARK) and found that most individuals with ASD experienced significant, ongoing disruptions to therapies. While some services were adapted to telehealth format, most participants were not receiving such services at follow-up, and those who were reported minimal benefit. Children under age five had the most severely disrupted services and lowest reported benefit of telehealth adaptation. Caregivers also reported worsening ASD symptoms and moderate family distress. Strategies to support the ASD community should be immediately developed and implemented., (© 2021. The Author(s).)

Because of the COVID-19 pandemic, in-person services for individuals with neurodevelopmental disabilities were disrupted globally, resulting in a transition to remote delivery of services and therapies. For individuals with neurogenetic conditions, reliance on nonclinical caregivers to facilitate all therapies and care was unprecedented. The study aimed to (1) describe caregivers' reported impact on their dependent's services, therapies, medical needs, and impact on themselves as a result of the COVID-19 pandemic and (2) assess the relationship between the extent of disruption of services and the degree of self-reported caregiver burden. Two online questionnaires were completed by caregivers participating in Simons Searchlight in April and May 2020. Surveys were completed by caregivers of children or dependent adults with neurodevelopmental genetic conditions in Simons Searchlight. Caregivers reported that the impact of the COVID-19 pandemic moderately or severely disrupted services, therapies, or medical supports. The majority of caregivers were responsible for providing some aspect of therapy. Caregivers reported "feeling stressed but able to deal with problems as they arise," and reported lower anxiety at follow-up. Caregivers reported that telehealth services were not meeting the needs of those with complex medical needs. Future surveys will assess if and how medical systems, educational programs, therapists, and caregivers adapt to the challenges arising during the COVID-19 pandemic.

Lay Abstract: We currently assume that the global mean age at diagnosis of autism spectrum disorder ranges from 38 to 120 months. However, this range is based on studies from 1991 to 2012 and measures have since been introduced to reduce the age at autism spectrum disorder diagnosis. We performed a systematic review and meta-analysis (statistical analysis that combines the results of multiple scientific studies) for studies published between 2012 and 2019 to evaluate the current age at autism spectrum disorder diagnosis. We included 56 studies that reported the age at diagnosis for 40 countries (containing 120,540 individuals with autism spectrum disorder). Results showed the current mean age at diagnosis to be 60.48 months (range: 30.90-234.57 months) and 43.18 months (range: 30.90-74.70 months) for studies that only included children aged ⩽10 years. Numerous factors that may influence age at diagnosis (e.g. type of autism spectrum disorder diagnosis, additional diagnoses and gender) were reported by 46 studies, often with conflicting or inconclusive results. Our study is the first to determine the global average age at autism spectrum disorder diagnosis from a meta-analysis. Although progress is being made in the earlier detection of autism spectrum disorder, it requires our constant attention.

Background: Computed tomography (CT), magnetic resonance imaging, and bone scintigraphy are second-line imaging techniques that are frequently used for the evaluation of patients with a clinically suspected scaphoid fracture. However, as a result of varying diagnostic performance results, no true reference standard exists for scaphoid fracture diagnosis. We hypothesized that the use of high-resolution peripheral quantitative CT (HR-pQCT) in patients with a clinically suspected scaphoid fracture could improve scaphoid fracture detection compared with conventional CT in the clinical setting., Methods: The present study included 91 consecutive patients (≥18 years of age) who presented to the emergency department with a clinically suspected scaphoid fracture between December 2017 and October 2018. All patients were clinically reassessed within 14 days after first presentation, followed by CT and HR-pQCT. If a scaphoid fracture was present, the fracture type was determined according to the Herbert classification system and correlation between CT and HR-pQCT was estimated with use of the Kendall W statistic or coefficient of concordance (W) (the closer to 1, the higher the correlation)., Results: The cohort included 45 men and 46 women with a median age of 52 years (interquartile range, 29 to 67 years). HR-pQCT revealed a scaphoid fracture in 24 patients (26%), whereas CT revealed a scaphoid fracture in 15 patients (16%). Patients with a scaphoid fracture were younger and more often male. The correlation between CT and HR-pQCT was high for scaphoid fracture type according to the Herbert classification system (W = 0.793; 95% confidence interval [CI], 0.57 to 0.91; p < 0.001) and very high for scaphoid fracture location (W = 0.955; 95%, CI 0.90 to 0.98; p < 0.001)., Conclusions: In the present study, the number of patients diagnosed with a scaphoid fracture was 60% higher when using HR-pQCT as compared with CT. These findings imply that a substantial proportion of fractures-in this study, more than one-third-will be missed by the current application of CT scanning in patients with a clinically suspected scaphoid fracture., Level of Evidence: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence., Competing Interests: Disclosure: The authors indicated that no external funding was received for any aspect of this work. On the Disclosure of Potential Conflicts of Interest forms, which are provided with the online version of the article, one or more of the authors checked “yes” to indicate that the author had a relevant financial relationship in the biomedical arena outside the submitted work (http://links.lww.com/JBJS/G169)., (Copyright © 2020 by The Journal of Bone and Joint Surgery, Incorporated.)

Professionals' limited knowledge on mental health and their stigmatizing attitudes toward mental illness can delay the diagnosis of autism. We evaluated the knowledge on Autism Spectrum Disorder (ASD) and stigmatizing attitudes in 93 physicians at Dutch Youth and Family Centers (YFC). These physicians screen for psychiatric symptoms in children. We show that their general ASD knowledge scored 7.1 (SD 1.2), but their specific ASD knowledge was only 5.7 (SD 1.7) (weighted means on 1-10 scale, 1 = least knowledge, 10 = most knowledge). Our physicians had positive attitudes toward mental illness (CAMI scores 2.18 (SD 0.33) to 2.22 (SD 0.40) on a 5-point Likert scale) but they had higher levels of stigmatizing attitudes than other Western healthcare professionals. Their levels were considerably lower than in non-Western professionals. We found no relations between ASD knowledge, stigmatizing attitudes and demographic variables. In conclusion, ASD knowledge and stigmatizing attitudes toward mental illness in Dutch YFC physicians require attention.

Background: Heart Rate Variability (HRV) represents efferent vagus nerve activity which is suggested to be inversely related to fundamental mechanisms of tumorigenesis and to be a predictor of prognosis in various types of cancer. HRV is also believed to predict the occurrence and severity of post-operative complications. We aimed to determine the role of pre-operative HRV as a prognostic factor in overall and cancer free survival in patients with colorectal cancer., Methods: Retrospective analysis was performed in a detailed dataset of patients diagnosed with primary colorectal cancer between January 2010 and December 2016, who underwent curative surgical treatment. HRV was measured as time-domain parameters (SDNN (Standard Deviation of NN-intervals) and RMSSD (Root Mean Square of Successive Differences)) based on pre-operative 10 second ECGs. Groups were created by baseline HRV: Low HRV (SDNN <20ms or RMSSD <19ms) and normal HRV (SDNN ≥20ms or RMSSD ≥19ms). Primary endpoints were overall and cancer free survival., Results: A total of 428 patients were included in this study. HRV was not significantly associated with overall survival (SDNN <20ms vs SDNN ≥20ms:24.4% vs 22.8%, adjusted HR = 0.952 (0.607-1.493), p = 0.829; RMSSD <19ms vs RMSSD ≥19ms:27.0% vs 19.5%, adjusted HR = 1.321 (0.802-2.178), p = 0.274) or cancer recurrence (SDNN <20ms vs ≥20ms:20.1% vs 18.7%, adjusted HR = 0.976 (0.599-1.592), p = 0.924; RMSSD <19ms vs ≥19ms, 21.5% vs 16.9%, adjusted HR = 1.192 (0.706-2.011), p = 0.511). There was no significant association between HRV and CEA-level at one year follow-up, or between HRV and occurrence of a post-operative complication or the severity of post-operative complications., Conclusions: Heart rate variability was not associated with overall or cancer free survival in patients with primary colorectal cancer who underwent curative surgical treatment. These results do not align with results found in studies including only patients with advanced cancer, which suggests that there is only an association in the other direction, cancer causing low HRV., Competing Interests: The authors have declared that no competing interests exist.

Introduction: Diagnosing scaphoid fractures remains challenging. High-resolution peripheral quantitative computed tomography (HR-pQCT) might be a potential imaging technique, but no data are available on its feasibility to scan the scaphoid bone in vivo., Methodology: Patients (≥18 years) with a clinically suspected scaphoid fracture received an HR-pQCT scan of the scaphoid bone (three 10.2-mm stacks, 61-μm voxel size) with their wrist immobilized with a cast. Scan quality assessment and bone contouring were performed using methods originally developed for HR-pQCT scans of radius and tibia. The contouring algorithm was applied on coarse hand-drawn pre-contours of the scaphoid bone, and the resulting contours (AUTO) were manually corrected (sAUTO) when visually deviating from bone margins. Standard morphologic analyses were performed on the AUTO- and sAUTO-contoured bones., Results: Ninety-one patients were scanned. Two out of the first five scans were repeated due to poor scan quality (40%) based on standard quality assessment during scanning, which decreased to three out of the next 86 scans (3.5%) when using an additional thumb cast. Nevertheless, after excluding one scan with an incompletely scanned scaphoid bone, post hoc grading revealed a poor quality in 14.9% of the stacks and 32.9% of the scans in the remaining 85 patients. After excluding two scans with contouring problems due to scan quality, bone indices obtained by AUTO- and sAUTO-contouring were compared in 83 scans. All AUTO-contours were manually corrected, resulting in significant but small differences in densitometric and trabecular indices (<1.0%)., Conclusions: In vivo HR-pQCT scanning of the scaphoid bone is feasible in patients with a clinically suspected scaphoid fracture when using a cast with thumb part. The proportion of poor-quality stacks is similar to radius scans, and AUTO-contouring appears appropriate in good- and poor-quality scans . Thus, HR-pQCT may be promising for diagnosis of and microarchitectural evaluations in suspected scaphoid fractures., (Copyright © 2019 The International Society for Clinical Densitometry. Published by Elsevier Inc. All rights reserved.)

Aims: Besides conventional radiographs, the use of MRI, CT, and bone scintigraphy is frequent in the diagnosis of a fracture of the scaphoid. However, which techniques give the best results remain unknown. The investigation of a new imaging technique initially requires an analysis of its precision. The primary aim of this study was to investigate the interobserver agreement of high-resolution peripheral quantitative CT (HR-pQCT) in the diagnosis of a scaphoid fracture. A secondary aim was to investigate the interobserver agreement for the presence of other fractures and for the classification of scaphoid fracture., Methods: Two radiologists and two orthopaedic trauma surgeons evaluated HR-pQCT scans of 31 patients with a clinically-suspected scaphoid fracture. The observers were asked to determine the presence of a scaphoid or other fracture and to classify the scaphoid fracture based on the Herbert classification system. Fleiss kappa statistics were used to calculate the interobserver agreement for the diagnosis of a fracture. Intraclass correlation coefficients (ICCs) were used to assess the agreement for the classification of scaphoid fracture., Results: A total of nine (29%) scaphoid fractures and 12 (39%) other fractures were diagnosed in 20 patients (65%) using HR-pQCT across the four observers. The interobserver agreement was 91% for the identification of a scaphoid fracture (95% confidence interval (CI) 0.76 to 1.00) and 80% for other fractures (95% CI 0.72 to 0.87). The mean ICC for the classification of a scaphoid fracture in the seven patients diagnosed with scaphoid fracture by all four observers was 73% (95% CI 0.42 to 0.94)., Conclusion: We conclude that the diagnosis of scaphoid and other fractures is reliable when using HR-pQCT in patients with a clinically-suspected fracture. Cite this article: Bone Joint J 2020;102-B(4):478-484.

Mosquitoes transmit pathogens that kill >700,000 people annually. These insects use body heat to locate and feed on warm-blooded hosts, but the molecular basis of such behavior is unknown. Here, we identify ionotropic receptor IR21a, a receptor conserved throughout insects, as a key mediator of heat seeking in the malaria vector Anopheles gambiae Although Ir21a mediates heat avoidance in Drosophila , we find it drives heat seeking and heat-stimulated blood feeding in Anopheles At a cellular level, Ir21a is essential for the detection of cooling, suggesting that during evolution mosquito heat seeking relied on cooling-mediated repulsion. Our data indicate that the evolution of blood feeding in Anopheles involves repurposing an ancestral thermoreceptor from non-blood-feeding Diptera., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)

Distal radius fractures (DRFs) occur in various complexity patterns among patients differing in age, gender, and bone mineral density (BMD). Our aim was to investigate the association of patient characteristics, BMD, bone microarchitecture, and bone strength with the pattern complexity of DRFs. In this study, 251 patients aged 50-90 years with a radiologically confirmed DRF who attended the Fracture Liaison Service of VieCuri Medical Centre, the Netherlands, between November 2013 and June 2016 were included. In all patients fracture risk factors and underling metabolic disorders were evaluated and BMD measurement with vertebral fractures assessment by dual-energy X-ray absorptiometry was performed. Radiographs of all DRFs were reviewed by two independent investigators to assess fracture pattern complexity according to the AO/OTA classification in extra-articular (A), partially articular (B), and complete articular (C) fractures. For this study, patients with A and C fractures were compared. Seventy-one patients were additionally assessed by high-resolution peripheral quantitative computed tomography. Compared to group A, mean age, the proportion of males, and current smokers were higher in group C, but BMD and prevalent vertebral fractures were not different. In univariate analyses, age, male gender, trabecular area, volumetric BMD (vBMD), and stiffness were associated with type C fractures. In multivariate analyses, only male gender (odds ratio (OR) 8.48 95% confidence interval (CI) 1.75-41.18, p = 0.008]) and age (OR 1.11 [95% CI 1.03-1.19, p = 0.007]) were significantly associated with DRF pattern complexity. In conclusion, our data demonstrate that age and gender, but not body mass index, BMD, bone microarchitecture, or strength were associated with pattern complexity of DRFs.© 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc. J Orthop Res 37:1690-1697, 2019., (© 2019 The Authors. Journal of Orthopaedic Research® Published by Wiley Periodicals, Inc.)

Introduction:: Peripherally inserted central catheters are venous devices intended for short to medium periods of intravenous treatment. Positioning of the catheter tip at the cavoatrial junction is necessary for optimum performance of a peripherally inserted central catheter. In this study, safety, effectiveness and cost-effectiveness of electrocardiographic-guided peripherally inserted central catheter positioning in a Dutch teaching hospital were evaluated., Methods:: All patients who received a peripherally inserted central catheter in 2016 using electrocardiographic guidance were compared to those where fluoroscopy guidance was used in a prospective non-randomized cohort study. Relevant data were extracted from electronic health records. Cost-effectiveness analysis was performed., Results:: A total of 162 patients received a peripherally inserted central catheter using fluoroscopy guidance and 103 patients using electrocardiographic guidance in 2016. No significant difference was found in malposition, infection or other complications between these groups. Due to personnel reduction and omission of fluoroscopy costs, cost reduction for each catheter insertion was €120 in the first year and, as a result of discounted acquisition costs, €190 in subsequent years., Discussion:: The positioning results and complication rate are comparable to the previously reported literature. The cost reduction may vary in different hospitals. Other benefits of the electrocardiographic-guided technique are omission of X-ray exposure and improved patient service., Conclusion:: Implementation of electrocardiographic-guided tip positioning for peripherally inserted central catheter was safe and effective in this study and led to an improved high value and cost-conscious care.

Introduction: Youth empowerment programs have increasingly gained attention in public health as emphasis shifts on children and adolescents as decision makers in their health and well-being. Adolescence obesity is among the public health concerns that require more active engagement at individual and community level while empowering adolescents to take charge of their own health. This study examines the influence of youth empowerment on nutritional and physical activity factors associated with adolescence obesity., Methods: Data were gathered through a self-administered survey among adolescents (N = 410) ages 11-15 years in three U.S. States - Kansas, Ohio and South Dakota., Results: Findings show that youth empowerment significantly influences adolescents' self-efficacy, perceptions for healthy food choice, healthy eating, attitudes towards physical activity and the overall motivation for health. Gender differences exist in adolescents' self-efficacy for physical activity whereas ethnicity played a role in perceived youth empowerment and perceived barriers to healthy eating. Age was also a significant contributor in efficacy for healthy food choice and perception of healthy food availability., Conclusions: This study suggests more focus on youth empowerment in interventions that seek to reduce obesity and improve adolescents' overall health by creating environments where they can play a more active decision-making role. With empowerment, adolescents are more likely to be motivated to adopt healthier dietary habits and engage more in physical activity. Further research would establish the impact of youth empowerment on obesity reduction and other public health problems that impact children across ages., (Copyright © 2018 The Foundation for Professionals in Services for Adolescents. Published by Elsevier Ltd. All rights reserved.)

Drug-induced liver injury (DILI) has been described with numerous nonsteroidal anti-inflammatory drugs (NSAIDs). Oral diclofenac has been associated with DILI more frequently than other NSAIDs and requires periodic monitoring of liver transaminases and judicious consideration of clinical signs and symptoms of hepatotoxicity. Here we describe a case in which elevated liver transaminases in a 79-year-old female returned to normal following discontinuation of topical diclofenac 1% gel. Using a widely accepted drug reaction causality instrument, a rating of "definite" was assigned given the temporal sequence of drug exposure and transaminase changes. Further study is warranted to better guide prescribing of topical NSAIDs.

Interstitial cystitis (IC) is a chronic pain disorder of the bladder that is often underdiagnosed and mistreated. The difficulties in diagnosis stem from numerous theories regarding pathophysiology and etiology, including the breakdown of the glycosaminoglycan (GAG) layer, altered permeability of the urothelium, uroinflammation, and neural up-regulation. Dysfunction of the bladder increases the struggle for proper treatment and continues to prove difficult for health care providers to correctly diagnose and manage IC. If diagnosed and/or managed inappropriately, IC may contribute to increased symptom burden and decreased quality of life with respect to activities of daily living. When evaluating a patient's clinical presentation in combination with predefined risk factors, a health care provider can better establish a true diagnosis of IC, which, in turn, leads to better management of IC-associated symptoms. This review will help health care providers better understand the disease process by discussing pathophysiology, pain pathways, and common symptoms of IC, with the goal of better aiding them in the proper diagnosis and treatment of patients with IC.

The aim of this study was to understand the diagnostic, service and lived experiences of families affected by ASD in Southeast Europe. A total of 758 caregivers from Albania, Bulgaria, Croatia and Turkey were surveyed from 2013 to 2015 about characteristics of the child with ASD; service encounters; and caregiver perceptions. The average age at first concern was 24.4 months (SD 11.8) and at diagnosis, 40.0 months (SD 19.0). Psychiatrists were the most common diagnostician; most children received some ASD-related service, most frequently speech and language therapy. Caregivers endorsed challenges in access to care and perceived stigma. Despite country differences, findings relative to age at first concern, disparities in access and service utilization, and stigma speak to common regional needs.

One of the most consistent findings in autism spectrum disorder (ASD) research is a higher rate of ASD diagnosis in males than females. Despite this, remarkably little research has focused on the reasons for this disparity. Better understanding of this sex difference could lead to major advancements in the prevention or treatment of ASD in both males and females. In October of 2014, Autism Speaks and the Autism Science Foundation co-organized a meeting that brought together almost 60 clinicians, researchers, parents, and self-identified autistic individuals. Discussion at the meeting is summarized here with recommendations on directions of future research endeavors.

The diagnosis of autism is often delayed, which translates into a missed opportunity to provide treatment during a critical developmental period. This study reviews studies that assessed factors associated with age at autism spectrum disorder diagnosis and provides recommendations on future research, programs, and policies to improve early detection. A search for all peer-reviewed articles containing the words autism, age, and diagnosis in either the title or abstract was performed. A total of 42 studies published from January 1990 through March 2012 were identified. Mean age at diagnosis for all autism spectrum disorders ranged from 38 to 120 months and has decreased over time. Factors associated with earlier diagnosis included greater symptom severity, high socioeconomic status, and greater parental concern about initial symptoms. Family interactions with the health and education systems prior to diagnosis also influenced age at diagnosis. Geographic variation in age at autism spectrum disorder diagnosis was identified in a number of studies, suggesting that community resources and state policies play a role in early identification. Early detection efforts should include enhanced parental and provider education on the early recognition of developmental problems, interventions aimed at streamlining the process from first concern to eventual diagnosis, and strategies that target underserved populations., (© The Author(s) 2013.)

Background: A reliable diagnosis of autism can be made as early as 24 months, yet in many children diagnoses are made much later. A delay in diagnosis translates into a missed opportunity to provide early intervention services and to improve outcomes. The aim of the current study was to review the literature on early detection approaches in primary care and other community settings in the United States., Methods: A search was conducted of the peer-reviewed and gray literature to identify studies published from January 1990 through January 2013 testing approaches to enhance the early detection of autism in community settings in the United States., Results: The search identified 40 studies describing 35 approaches, which were grouped into the following categories: awareness (n = 4), routine screening (n = 21), and practice improvement to enhance screening (n = 10). Awareness approaches were associated with positive changes in knowledge of autism-related topics. Routine screening yielded high or increased rates of screening and referrals; however, few studies assessed the effect of screening on age at diagnosis or services enrollment. Practice improvement approaches resulted in increased screening and referral rates and highlighted the importance of adopting a multipronged approach to enhance early detection., Conclusions: Although studies that tested screening approaches in community settings found positive results, the effectiveness of such efforts on reducing time to diagnosis and services enrollment remains largely untested. The fact that few studies reported outcomes beyond rates of referral indicates the need for enhanced methodological rigor, particularly with respect to length of follow-up and quality of measures used., (Copyright © 2014 American Academy of Child and Adolescent Psychiatry. Published by Elsevier Inc. All rights reserved.)

The aims of this retrospective, descriptive study were to describe clients served by a buprenorphine program in a community-based recovery center and to present initial treatment outcomes. A record review was conducted for clients treated from July 2010 to August 2011. Client demographic, health, substance use, and treatment history data were abstracted from the records of the first 78 clients served. Buprenorphine and opiate use data were collected via urine toxicology reports, collected weekly among clients who remained enrolled in treatment. The average percentages of weeks spent opiate free and buprenorphine compliant were 83% (SD = 26%) and 95% (SD = 13%), respectively. When positive heroin toxicology and negative buprenorphine toxicology were replaced for the missing/unknown data, the average percentages of opiate-abstinent weeks and buprenorphine compliance were 60% (SD = 34%) and 74% (SD = 28%), respectively. Roughly half of all clients (49%) were successfully transitioned to continue treatment with buprenorphine in a primary care setting. Findings from this study demonstrate that buprenorphine treatment for opiate dependence can be incorporated into a community-based recovery center with high rates of opiate abstinence and treatment adherence.

This study estimated compliance with American Academy of Pediatrics (AAP) guidelines for well-child care and the association between compliance and age at diagnosis in a national sample of Medicaid-enrolled children with autism (N = 1,475). Mixed effects linear regression was used to assess the relationship between compliance and age at diagnosis. Mean age at diagnosis was 37.4 (SD 8.4) months, and mean compliance was 55 % (SD 33 %). Children whose care was compliant with AAP guidelines were diagnosed 1.6 months earlier than children who received no well-child care. Findings support that the timely receipt of well-child care may contribute to earlier detection. Additional research on the contribution of compliance, well-child visit components and provider characteristics on the timely diagnosis of autism is needed.

This is the first of two articles about improving end of life care for terminally ill patients in a district general hospital. The article describes a hospice transfer service developed by joint working between staff at a medical assessment unit and a hospice to improve end of life care for patients who otherwise might die in the medical assessment unit. It discusses the care received by patients in both settings, and the practicalities of offering patients the option of rapid transfer to the hospice for end of life care, where the emphasis of care is on palliation not acute intervention. The second article explores the ethical, legal and practical considerations involved in developing the service.

BACKGROUND: This study examined the prevalence and correlates of schizophrenia spectrum disorders (SSD) among a national sample of 9006 children. METHODS: Clinician-assigned diagnoses were used to divide the sample into two groups: children with SSD and children with other Axis I disorders. RESULTS: Three percent of the sample had a SSD diagnosis. African American (OR=1.71, 95% CI: 1.11, 2.65) and Hispanic race/ethnicity (OR=1.96, 95% CI: 1.31, 2.94), a greater number of comorbid psychiatric diagnoses (three diagnoses, OR=2.22, 95% CI: 1.49, 3.31), a history of attempting suicide (OR=1.45; 95% CI: 1.05, 2.02), and past residential treatment (OR=1.59; 95% CI: 1.11, 2.28) were all associated with increased odds of SSD diagnosis. CONCLUSIONS: Although schizophrenia spectrum disorders in youth are rare, children with these disorders present with a distinct risk profile that may inform service planning and delivery and assist in identifying individuals early in the course of their illness.

Growing interest in autism spectrum disorder (ASD) research requires increasingly large samples to uncover epidemiologic trends; such a large dataset is available in a national, web-based autism registry, the Interactive Autism Network (IAN). The objective of this study was to verify parent-report of professional ASD diagnosis to the registry's database via a medical record review on a sample of IAN Research participants. Sixty-one percent of families agreed to participate; 98% (n = 116) of whom provided documentation verifying a professionally diagnosed ASD. Results of this study suggest that information collected from parents participating in IAN Research is valid, participants can be authenticated, and that scientists can both confidently use IAN data and recruit participants for autism research.

The study's objectives were to assess diagnostic stability of initial autism spectrum disorder (ASD) diagnoses in community settings and identify factors associated with diagnostic instability using data from a national Web-based autism registry. A Cox proportional hazards model was used to assess the relative risk of change in initial ASD diagnosis as a function of demographic characteristics, diagnostic subtype, environmental factors and natural history. Autistic disorder was the most stable initial diagnosis; pervasive developmental disorder-not otherwise specified was the least stable. Additional factors such as diagnosing clinician, region, when in time a child was initially diagnosed, and history of autistic regression also were significantly associated with diagnostic stability in community settings. Findings suggest that the present classification system and other secular factors may be contributing to increasing instability of community-assigned labels of ASD.

Behavioral and emotional strengths are important to consider when understanding youth mental health and treatment. This study examined the association between youth strengths and functional impairment, and whether this association is modified by race/ethnicity. Multinomial logistic regression models were used to estimate the effects of strengths on impairment, and examine whether race and ethnicity modified this relationship in 8,129 Caucasian, African American, Hispanic, and American Indian/Alaska Native youth, between 5 and 18 years of age. Results suggest that youth with average and above average strengths were less likely to have impairment compared to youth with below average strengths. Race and ethnicity modified this relationship in both expected and unexpected ways. Among youth with average and above average strengths, racial and ethnic minority youth appear to have more impairment than Caucasian youth. However, among youth with below average strengths, racial and ethnic minority youth have less impairment than Caucasian youth. Findings highlight the importance of incorporating strengths-based approaches in youth mental health treatment and the need for further research to understand the specific nature of strengths as it effects impairment across racial/ethnic groups. Implications and recommendations are discussed.

This author argues that youth sports can move beyond the dichotomy of cooperation versus competition by redefining competition. This can be accomplished by considering the development of cooperative skills and achievement motivation. The article addresses how cooperative skills can be taught within a competitive sport. First, it is important to understand how children and youth understand and process competition based on their developmental stage. Parents need to consider whether a child is mentally, emotionally, socially, and physically mature enough to participate in an organized sport. Readiness for a sport is just as important as readiness for school. Teaching cooperative skills within a competitive context involves a focus on personal development rather than performance. By asking themselves a series of developmental questions, such as, "Is the sport appropriate for the developmental age of the child?" parents and coaches can form realistic expectations of young athletes. Motivation is also a key determinant of a child's readiness for youth sports and competition. Children want to play a sport when they feel competent. It is up to parents and coaches to create a motivational climate that is focused on doing one's best and not on external rewards like winning. Children and youth receive specific and constructive feedback that focuses on improvement in this type of climate. The author also discusses three models of competition: the military model, the reward model, and the partnership model. The partnership model is the approach that balances competition in youth sports. The author concludes by introducing the "athletic square" model as an important and appropriate way to promote youth sports.

3,4-Methylenedioxymethamphetamine, or "Ecstasy," is a drug commonly used at "rave" parties to heighten energy and intimacy. Although its complications have been well described in Europe, including less common side effects such as hepatic failure and rhabdomyolysis, physicians in the United States have less experience with this drug because of the shorter duration of its use in this country. We present a case of an active duty soldier who was admitted for acute hepatitis secondary to Ecstasy ingestion and describe its proposed pathophysiology. We believe that with the increased use of Ecstasy in the United States, especially among younger patients, including soldiers, military physicians will need to be more familiar with this potentially deadly drug.

Changes after 2 years in a Head Start Family Service Center Demonstration Project were assessed through pre-implementation and post-implementation interviews with 80 parents of Head Start children to evaluate changes during the project noted for the children's parents. Compared with parents in regular Head Start, parents in the supplementary Family Service Center project reported more contact with staff, increased their functional literacy scores, and increased their family incomes. The percentage of these parents with high depression scores decreased. These changes encourage implementation of more intensive social services within Head Start programs as a means of effectively assisting Head Start parents.

The internal structure of the Center for Epidemiologic Studies--Depression Scale was examined within the context of a three-year longitudinal study of 80 low-income parents of young children. The baseline, first-year, and second-year follow-up home interviews included the scale. Principal components factor analyses with varimax rotation yielded six factors for the baseline data, and five factors for the follow-up data with different items loading on different factors each year suggesting some instability of the factors. Cronbach alpha estimates of the internal consistency of the original factors showed satisfactory values for Depressed Affect, Positive Affect, and possibly Somatic, but not for Interpersonal. However, alpha for the total score was very strong. Positive Affect and the total score also showed stability over the three administrations. These results question the use of the original factor scores for the CES-Depression as subscales but support the use of the total score as a measure of depression.