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The Undiagnosed Disease Program in South Africa (UDP) sought to prospectively evaluate the clinical utility of exome sequencing (ES) in a phenotypically diverse, multi-ethnic cohort of South African patients with suspected rare genetic disorders. ES was undertaken in 100 sequential patients (93 singletons, 3 duos, and 4 trios) recruited to the UDP at Stellenbosch University. The data were analyzed through two separate bioinformatics pipelines (EVIDENCE from 3 billion and our in-house pipeline). A definitive diagnosis could be reached in 51% (51/100) patients, with 46% (46/100) patients having either pathogenic or likely pathogenic single-nucleotide variants/indels (SNVs/indels), and 5 patients with likely-pathogenic copy number variants (CNVs) (5/100). The CNVs were subsequently confirmed on microarray or MLPA analysis. Detailed phenotyping and HPO terms enabled analysis and variant identification. Twenty-five novel variants in 22 genes are reported here. We provide data from the first year of this UDP and show that even amongst mainly singletons from an understudied, diverse African population, ES is a valuable diagnostic tool, especially if it includes CNV analysis. The remaining undiagnosed patients present a unique opportunity for further research and novel gene discovery.

Poor survival of grafted cells is the major impediment of successful cell-based therapies for bone regeneration. Implanted cells undergo rapid death in an ischemic environment largely because of hypoxia and metabolic stress from glucose deficiency. Understanding the intracellular metabolic processes and finding genes that can improve cell survival in these inhospitable conditions are necessary to enhance the success of cell therapies. Thus, the purpose of this study was to investigate changes of metabolic profile in glucose-deprived human bone marrow stromal/stem cells (hBMSCs) through metabolomics analysis and discover genes that could promote cell survival and osteogenic differentiation in a glucose-deprived microenvironment. Metabolomics analysis was performed to determine metabolic changes in a glucose stress metabolic model. In the absence of glucose, expression levels of all metabolites involved in glycolysis were significantly decreased than those in a glucose-supplemented state. In glucose-deprived osteogenic differentiation, reliance on tricarboxylic acid cycle (TCA)-predicted oxidative phosphorylation instead of glycolysis as the main mechanism for energy production in osteogenic induction. By comparing differentially expressed genes between glucose-deprived and glucose-supplemented hBMSCs, NR2F1 (Nuclear Receptor Subfamily 2 Group F Member 1) gene was discovered to be associated with enhanced survival and osteogenic differentiation in cells under metabolic stress. Small, interfering RNA (siRNA) for NR2F1 reduced cell viability and osteogenic differentiation of hBMSCs under glucose-supplemented conditions whereas NR2F1 overexpression enhanced osteogenic differentiation and cell survival of hBMSCs in glucose-deprived osteogenic conditions via the protein kinase B (AKT)/extracellular signal-regulated kinase (ERK) pathway. NR2F1-transfected hBMSCs significantly enhanced new bone formation in a critical size long-bone defect of rats compared with control vector-transfected hBMSCs. In conclusion, the results of this study provide an understanding of the metabolic profile of implanted cells in an ischemic microenvironment and demonstrate that NR2F1 treatment may overcome this deprivation by enhancing AKT and ERK regulation. These findings can be utilized in regenerative medicine for bone regeneration. © 2022 American Society for Bone and Mineral Research (ASBMR).

BackgroundCondom use remains the most effective behavioural method for the prevention of HIV and unplanned pregnancies. However, condom use remains inconsistent among young people. Exploring the condom use decision-making processes that adolescents engage in might provide information that would assist in the prevention of many challenges related to poor sexual and reproductive health outcomes. This study therefore aimed to explore the factors that influenced decision-making about sexual debut and condom use of adolescents from two schools in the Western Cape, South Africa.MethodsA sample of 16 adolescents were selected using purposive sampling. Data were collected using semi-structured, individual interviews. Thematic analysis was used to analyse the data generated.ResultsThe link between sexual debut and affective processes was frequently discussed in condom use decision-making. Decisions about sexual debut were influenced by the belief that sex was a perceived symbol of ‘true love’ on the one hand, and respect for perceived parental expectations of age-appropriate sex, on the other. Condom use decision-making was shaped by adolescents’ concerns about their future and lack of stability in their lives. Adolescents’ fears of pregnancy, parenthood and disease shaped their condom use decision-making. It became evident that rational and affective decision-making in condom use choice were not mutually exclusive, but that these processes happened simultaneously.ConclusionsThe study highlighted the role of affective states as part of the process of examining alternatives when deciding to use a condom or not. Interventions to strengthen condom use decision-making should therefore incorporate not only rational but also affective processes to improve adolescent sexual and reproductive outcomes.

An understanding of the common MRI findings observed after decompression surgery is important. However, to date, no study addressing this has been published. The aim of this study was to analyze and describe the immediate postoperative MRI findings after lumbar decompression surgery. We retrospectively analyzed the immediate postoperative MRIs of 121 consecutive patients who underwent lumbar decompression surgery between July 2017 and June 2018. Changes in stenosis at the decompressed and adjacent levels, epidural fat edema, epidural and subdural fluid collections, nerve root swelling, facet joint effusions, intervertebral disc signal, and paravertebral muscle edema were correlated with clinical characteristics. Both groups had reduced central canal stenosis postoperatively (p 0.001) but worsened stenosis at adjacent segments. Fluid collection, hemorrhagic or non-hemorrhagic, at the laminectomy site was the commonest finding (one-level: 73.8%, two-level: 88.5%), with a higher percentage of severe central canal compromise in the two-level decompression group (p = 0.003). Other postoperative MRI findings, such as epidural fat edema, nerve root swelling, subdural fluid collection, and facet joint effusion, were noted without statistical significance. In conclusion, even with successful decompression for lumbar canal stenosis, increased central canal stenosis at adjacent segments is common on immediate postoperative MRI scans, showing no statistically significant correlation with the immediate postoperative outcome. Postoperative fluid collection at the laminectomy site is the commonest imaging finding, and higher rates of hemorrhagic fluid and more severe central canal compromise occur in two-level decompression, but rarely cause clinical problems.

We evaluated the feasibility of using the Hounsfield unit (HU) value of the vertebral body to predict screw loosening in the thoracic spine. Consecutive patients who underwent thoracic spinal fusion surgery (from 2014 to 2020) were retrospectively identified. Patients with pedicle screw loosening in the upper instrumented vertebra (UIV) on postoperative computed tomography were included in the “loosening” group. The control group comprised an equal number of age-, sex-, and UIV-matched patients without screw loosening. Preoperative HU values at the UIV and lumbar T-scores were compared between the groups; receiver operating characteristic curves were constructed for HU values and T-scores to predict screw loosening, and the best cutoff values were determined. The same statistical analyses were performed for each subgroup, i.e., upper (T1–T4) and lower (T9–T12) thoracic levels. Forty-six patients each were included in the loosening and control groups. A significant between-group difference of HU values was noted for the lower thoracic UIV (loosening = 99.3, control = 126.3; p = 0.02) but not for the upper thoracic UIV (loosening = 171.8, control = 146.0, p = 0.70). T-scores did not differ between the groups for the lower (p = 0.14) and upper (p = 0.56) thoracic UIV. For the lower thoracic UIV, the area under the receiver operating characteristic curve was 0.660 for HUs (p = 0.01; 95% confidence interval [CI] 0.541–0.766) and 0.601 (p = 0.13; 95% CI 0.480–0.713) for T-scores. The optimal cutoff value for HUs was 126.3. Using this cutoff, HU values showed a better positive predictive value, negative predictive value, and accuracy compared to T-scores in predicting screw loosening.

Background/Aims: Sacroiliitis is a frequent extraintestinal manifestation of in flammatory bowel diseases (IBDs). This study aimed to assess the prevalence of sacroiliitis using a validated screening tool based on abdominopelvic computed tomography (APCT) in Korean patients with Crohn’s disease (CD) and examine potential associations between clinical characteristics and sacroiliitis. Methods: One hundred five patients with CD undergoing APCT for any indica tion at an IBD clinic were matched 1:1 for age and sex with 105 controls without underlying chronic illnesses. Using a validated APCT screening tool that defines sacroiliitis as either ankylosis or a total erosion score (TES) ≥ 3, all computed to mography scans were assessed by two independent, blinded radiologists. We com pared the prevalence of sacroiliitis between CD patients and controls and clinical characteristics between CD patients with and without sacroiliitis. Results: The prevalence of sacroiliitis was significantly higher in CD patients than in controls (13.3% vs. 4.8%, p = 0.030). All subjects with sacroiliitis had a TES ≥ 3, but no ankylosis. The assessment of sacroiliitis in APCT showed excellent in terreader reliability (Cohen’s kappa = 0.933 for presence of sacroiliitis). Sacroiliitis in CD patients was bilateral and asymptomatic. There were no significant associ ations between sacroiliitis and any demographic data or clinical characteristics in these patients. Conclusions: The prevalence of APCT-detected sacroiliitis in CD patients was higher than that in controls, but the condition was asymptomatic. The clinical significance of asymptomatic sacroiliitis in Korean CD patients remains unclear.

There is a large assessment and treatment gap in child and adolescent mental health services, prominently so in low- and middle-income countries, where 90% of the world’s children live. There is an urgent need to find evidence-based interventions that can be implemented successfully in these low-resource contexts. This pre-pilot study aimed to explore the barriers and facilitators to implementation as well as overall feasibility of Parent–Child Interaction Therapy (PCIT) in South Africa. A reflective and consensus building workshop was used to gather South African PCIT therapist (N = 4) perspectives on barriers, facilitators, and next steps to implementation in that country. Caregiver participants (N = 7) receiving the intervention in South Africa for the first time were also recruited to gather information on overall feasibility. Facilitators for implementation, including its strong evidence base, manualisation, and training model were described. Barriers relating to sustainability and scalability were highlighted. Largely positive views on acceptability from caregiver participants also indicated the promise of PCIT as an intervention in South Africa. Pilot data on the efficacy of the treatment for participating families are a next step. These initial results are positive, though research on how implementation factors contribute to the longer-term successful dissemination of PCIT in complex, heterogeneous low-resource settings is required.

To determine the association of meniscal flounce with the pattern and location of the meniscal tear, concomitant ligamentous injury, amount of knee joint effusion, and flexion and rotation angles. A total of 283 knees of 280 patients were retrospectively reviewed over a 9-month period. Thirty-one magnetic resonance images of patients with meniscal flounce were compared with those of age- and sex-matched control group (n = 62) without meniscal flounce. The presence of meniscal tear was evaluated and, if present, its location and pattern were recorded. The amount of joint effusion was graded, and the joint angle was measured. The Fisher’s exact, Cochran-Armitage trend, and t tests were performed to compare the findings between the two groups. The decision tree analysis was employed to determine the most significant factor of meniscal flounce. Meniscal flounce was present in 11.0% (31/283) of the adult population. Approximately 80.6% of meniscal flounce occurred in the torn medial menisci. The presence of meniscal flounce was significantly associated with tears at the body (p = 0.007), posterior horn (p = 0.001), and meniscocapsular junction (p = 0.002) of the medial meniscus. The decision tree analysis revealed that the posterior horn tear of the medial meniscus was the most significant predictor of meniscal flounce. The most significant factor associated with meniscal flounce is tear at the posterior horn of the medial meniscus, followed by tear at the meniscocapsular junction.

To develop and validate prediction models to differentiate acute and chronic vertebral compression fractures based on radiologic and radiomic features on CT.This study included acute and chronic compression fractures in patients who underwent both spine CT and MRI examinations. For each fractured vertebra, three CT findings ([1] cortical disruption, [2] hypoattenuating cleft or sclerotic line, and [3] relative bone marrow attenuation) were assessed by two radiologists. A radiomic score was built from 280 radiomic features extracted from non-contrast-enhanced CT images. Weighted multivariable logistic regression analysis was performed to build a radiologic model based on CT findings and an integrated model combining the radiomic score and CT findings. Model performance was evaluated and compared. Models were externally validated using an independent test cohort.A total to 238 fractures (159 acute and 79 chronic) in 122 patients and 58 fractures (39 acute and 19 chronic) in 32 patients were included in the training and test cohorts, respectively. The AUC of the radiomic score was 0.95 in the training and 0.93 in the test cohorts. The AUC of the radiologic model was 0.89 in the training and 0.83 in the test cohorts. The discriminatory performance of the integrated model was significantly higher than the radiologic model in both the training (AUC, 0.97; p0.01) and the test (AUC, 0.95; p=0.01) cohorts.Combining radiomics with radiologic findings significantly improved the performance of CT in determining the acuity of vertebral compression fractures.

Background Despite transforaminal epidural steroid injection (ESI) being the first choice in patient with recurrent herniated intervertebral disc (HIVD), efficacy of ESI in those patients are not well established. Herein, we evaluate the effectiveness and outcome predictors of fluoroscopic transforaminal ESI for recurrent HIVD. Methods Seventy-seven patients (48 male; mean age, 51.3 years) with recurrent lumbar HIVD were included and divided into three groups according to initial treatment: conservative treatment, transforaminal ESI, and immediate surgery. ESI effectiveness was evaluated by operation rates, injection numbers in 6 months, and pain reduction (visual analog scale (VAS) scores). Clinical and MRI variables were analyzed as possible outcome predictors. Each subject in the transforaminal ESI group was individually matched to two patients with initial HIVD (control group). Results In the transforaminal ESI group (n = 37), 20 patients (54.1%) did not undergo reoperation. The initial and follow-up VAS scores were significantly higher in the reoperation group (p = 0.014, p = 0.019, respectively). Patients with either paresthesia or motor weakness (12/19, 63.2%) had a significantly higher reoperation rate than patients with only pain (5/18, 27.8%; p = 0.031). Extruded disc ratios ≥2.0 were significantly higher in the reoperation group (10/17, 58.8%; p = 0.048). The reoperation rate in the transforaminal ESI group (17/37, 45.9%) was higher than the operation rate in the control group (6/73, 8.2%; p.001). Conclusion Transforaminal ESI was effective in reducing radicular pain in patients with recurrent HIVD. Approximately 54% of patients did not undergo reoperation. An extruded disc ratio ≥2.0 and paresthesia or motor weakness were poor outcome predictors.

Background and purpose Spinal cord infarction (SCI) is difficult to diagnosis using MRI findings. We aimed to suggest the optimal timing of MRI studies for diagnosing SCI. Materials and methods This retrospective study was approved by our institutional review board. The requirement for informed consent was waived. MRI scans of SCI patients diagnosed between January 2015 and August 2019 were enrolled in the SCI group and subdivided according to the interval between symptom onset and time of MRI scan (A, within 6 h; B, 6–12 hours; C, 12–24 hours; D, 24–72 hours; E, 3–7 days). Three radiologists analyzed the T2WI scans and evaluated the confidence level of diagnosing SCI using a five-point Likert scale: 1, certainly not; 2, probably not; 3, equivocal; 4, probably yes; 5, certainly yes. Scores of 4 and 5 were defined as “T2WI-positive SCI” and scores of 1–3 were defined as “T2WI-negative SCI”. Results The SCI group included 58 MRI scans of 34 patients (mean age, 60.6 ± 14.0 years; 18 women). The T2WI positivity rate was 72.4% (42/58). In contrast to the other subgroups, subgroup A included fewer cases of T2WI-positive SCI (1/4, 25%) than T2WI-negative SCI. A confidence score of 5 was the most common in subgroup D (4/27, 14.8%). Among the 12 patients who underwent MRI studies more than twice, confidence scores increased with time. Conclusion In patients with suspected SCI showing equivocal initial MRI findings, follow-up MRI studies are helpful, especially when performed between 24 and 72 hours after symptom onset.

Background Optimal intervals between repeat colonoscopies could improve patient outcomes and reduce costs. We evaluated: (a) concordance between clinician and guideline recommended colonoscopy screening intervals in Winnipeg, Manitoba, (b) clinician opinions about the utility of an electronic decision-making tool to aid in recommending screening intervals, and (c) the initial use of a decision-making smartphone/web-based application. Methods Clinician endoscopists and primary care providers participated in four focus groups (N = 22). We asked participating clinicians to evaluate up to 12 hypothetical scenarios and compared their recommended screening interval to those of North American guidelines. Fisher’s exact tests were used to assess differences in agreement with guidelines. We developed a decision-making tool and evaluated it via a pilot study with 6 endoscopists. Result 53% of clinicians made recommendations that agreed with guidelines in ≤ 50% of the hypothetical scenarios. Themes from focus groups included barriers to using a decision-making tool: extra time to use it, less confidence in the results of the tool over their own judgement, and having access to the information required by the tool (e.g., family history). Most were willing to try a tool if it was quick and easy to use. Endoscopists participating in the tool pilot study recommended screening intervals discordant with guidelines 35% of the time. When their recommendation differed from that of the tool, they usually endorsed their own over the guideline. Conclusions Endoscopists are overconfident and inconsistent with applying guidelines in their polyp surveillance interval recommendations. Use of a decision tool may improve knowledge and application of guidelines. A change in practice may require that the tool be coupled with continuing education about evidence for improved outcomes if guidelines are followed.

To analyze the incidence and characteristics of intra-articular facet joint injection (FJI)–related adverse events requiring hospitalization and emergency room visits. From January 2007 to December 2017, a total of 11,980 FJI procedures in 6066 patients (mean age 66.8 years, range 15–97 years, M:F = 2004:4062) were performed in our department. Of these, we retrospectively reviewed 489 cases in 432 patients who were hospitalized or visited the emergency room within a month of FJI. FJI-related adverse events were classified as procedure-related complications, drug-related systemic events, or uncertain etiology events, on the basis of consensus of two spine radiologists. This is a descriptive study without statistical analysis. There were 101 FJI-related adverse event cases in 99 patients (mean age 71.8 years, range 39–97 years, M:F = 39:60). The overall incidence of FJI-related adverse events was 0.84% (101/11,980) per case and 1.63% (99/6066) per patient. The incidence of procedure-related complications and drug-related systemic adverse events was 0.07% (8/11,980) and 0.15% (18/11,980), respectively; the rate of uncertain etiology events was 0.63% (75/11,980). All eight procedure-related complication cases involved major complications. There are seven cases of infectious spondylitis and one was progression of systemic aspergillosis to the spine. One patient died of an uncontrolled infection with infective endocarditis, and two patients experienced partial recovery with neurological sequelae. The overall incidence of FJI-related adverse events is low, and procedure-related major complications are rare without dural puncture or epidural hematoma. Nevertheless, infection can occur, resulting in serious outcomes. • The incidence of FJI-related adverse events requiring hospitalization or ER visit was 0.84%. • The incidence of major procedure-related complications was 0.07%. • All major complications were associated with infection and there were no cases of epidural hematoma.

We propose to use cRFP (common Repository of FBS Proteins) in the MS (mass spectrometry) raw data search of cell secretomes. cRFP is a small supplementary sequence list of highly abundant fetal bovine serum proteins added to the reference database in use. The aim behind using cRFP is to prevent the contaminant FBS proteins from being misidentified as other proteins in the reference database, just as we would use cRAP (common Repository of Adventitious Proteins) to prevent contaminant proteins present either by accident or through unavoidable contacts from being misidentified as other proteins. We expect it to be widely used in experiments where the proteins are obtained from serum-free media after thorough washing of the cells, or from a complex media such as SILAC, or from extracellular vesicles directly.

To analyze the causes of pain, imaging characteristics, and therapeutic effect of spinal injection in patients with extreme low back pain or sciatica. We analyzed 381 consecutive patients with extreme low back pain or sciatica visiting our spinal intervention center between January and December 2017. Clinical and imaging characteristics were analyzed. The treatment response, defined as a numerical pain rating scale decrease of ≥ 30%, was measured. Fisher’s exact test was performed to identify the association between the injection response and subsequent lumbar surgery rate. The most frequent cause of pain was spinal stenosis, followed by herniated intervertebral disc, facet osteoarthritis, and osteoporotic compression fracture. A herniated intervertebral disc was the most common disorder in patients

Empowering families of children with autism spectrum disorder through education and training is best practice. A wide range of Parent Education and Training programmes are delivered around the globe, but there is limited knowledge about the characteristics of these programmes, or about the research methods and outcomes used to evaluate them, particularly in countries outside the United States. We, therefore, performed a scoping review of all peer-reviewed Parent Education and Training publications outside the United States. A search was conducted between March and May 2017. Four reviewers extracted data and performed a mixed-methods quality appraisal of publications. Thirty-seven publications representing 32 unique programmes were identified. Publications described a highly diverse range of Parent Education and Training programmes across 20 countries and all continents except South America. The majority were group-based, but varied significantly in goals, modalities and duration. The majority of studies (86.4%) reported positive outcomes in relation to the core study objectives and only two studies reported some negative findings. Quality appraisal rated only 27% of studies to have met all the methodological quality criteria. Implementation factors such as manualisation, fidelity and cost were commented on infrequently. In spite of the clear need for Parent Education and Training programmes, our findings show that the research evidence-base in autism spectrum disorder outside the United States is relatively small, non-representative and in need of methodological quality improvements.

Objective To determine the usefulness of adding contrast-enhanced (CE) magnetic resonance imaging (MRI) to conventional MRI for evaluation of spinal metastases. Materials and methods One-hundred-and-two whole spine MR examinations, obtained for metastasis work-up within a 2-month period, from 65 men and 37 women (mean age, 64 years) with extra-spinal tumor, who also underwent CE-MRI, were retrospectively evaluated by three radiologists. The number of spine segments with bone marrow involvement was interpreted using a 3-point confidence scale (probable metastasis, equivocal, probably benign) during session 1 (conventional imaging) and session 2 (addition of CE-MRI to conventional imaging). The patients were assigned to 14 categories based on the changes in confidence rating between sessions 1 and 2; these were aggregated to four groups indicating the degree of usefulness of CE-MRI: definitely useful, equivocal, not useful, and presumed non-metastatic groups. Clinical information, metastatic bone type, the number of probably metastatic segments, and anatomical level and position were compared among the former three groups. Results The readers assigned 39–53% of cases to the definitely useful group. The number of probably metastatic segments differed significantly among the three groups for all readers (p ≤ 0.046). Age, sex, primary cancer, metastatic bone type, and anatomical level and position were similar. Conclusion Adding CE-MRI to conventional MRI was useful for objectively detecting and characterizing spinal segments with metastases in 39–53% of cases. However, there were no clinical or radiological factors that could predict the usefulness of CE-MRI in evaluating spinal metastases, except for the number of metastatic segments.

To evaluate the usefulness of whole-tumor ADC histogram analysis based on entire tumor volume in determining the histologic grade of STS (soft tissue sarcoma)s.From January 2015 to December 2020, 53 patients with STS who underwent preoperative magnetic resonance imaging, including diffusion weighted imaging and ADC maps (b = 0 and 1400 s/mmEight patients with low-grade STS (15.1%) and 45 with high-grade STS (26.4% [14/53] for grade II; 58.5% [31/53] for grade III) were included. High-grade STS showed positive skewness and low-grade STS showed negative skewness (0.503 vs -0.726, p=.001). High-grade STS showed lower mean ADC (p =.03) and 5th to 50th percentile values (p ≤. 03) than those of low-grade STS. Positive skewness was an independent predictor of high-grade STS (odds ratio: 6.704, p=.002) with 84.4% sensitivity and 87.5% specificity (cut-off values -0.1757, AUC = 0.842).Skewness is the most promising histogram parameter for discriminating high-grade from low-grade STS. The mean ADC values and lower half of percentile values are helpful for differentiating high from low-grade STSs.

The objective of our study was to evaluate the association between anterior tibial translation and injuries on the posterior horn medial meniscus (PHMM) and the integrity of the brake stop mechanism of the PHMM in the anterior cruciate ligament (ACL)-deficient knee.This retrospective study included 85 consecutive patients with an arthroscopically confirmed complete ACL tear. Anterior tibial translation was quantitatively measured using sagittal MRI at the midpoint of the lateral femoral condyle. The "uncovered medial meniscus" sign was considered positive if a vertical line tangent to the posteriormost margin of the medial tibial plateau intersected the PHMM at the midpoint of the medial femoral condyle on sagittal MRI. Concomitant injuries on the structures of the posteromedial and posterolateral corners of the knee, including PHMM tear and meniscal ramp lesion, were recorded. Stratified subgroup analysis and multivariable regression analysis were performed to identify factors associated with anterior tibial translation.The uncovered medial meniscus sign was positive in 21.2% (18/85) of patients and was significantly associated with anterior tibial translation. In the stratified subgroup analysis and multivariable regression analysis, positive uncovered medial meniscus sign consistently showed a significant association with anterior tibial translation and generated an additional 2.8 mm of anterior tibial translation. Other injuries, including PHMM tear and meniscal ramp lesion, were not associated with anterior tibial translation.The uncovered medial meniscus sign showed a statistically significant correlation with anterior tibial translation and could be a useful marker for the lost brake stop mechanism of PHMM in the ACL-deficient knee.

COVID-19 has put the in-vitro-diagnostic community under an unprecedented spotlight, with a global requirement for accurate SARS-CoV-2 tests. This review will outline technological responses to this need and the analytical considerations required for their translation to routine use.SARS-CoV-2 diagnostic solutions directly detect the virus or measure host-derived surrogate markers of infection. With pressure upon supply chains for the 'traditional' molecular approaches, a wide variety of analytical tools spanning the molecular, serology, imaging and chemistry space are being developed, including high throughput solutions and simplified near-patient formats.The unique genetic nature of SARS-CoV-2 means high analytical specificity is achievable by most diagnostic formats. However, clinical sensitivity assessment is complicated by wide discrepancies in analytical range and challenges associated with standardising these differences. When coupled with the acute nature of SARS-CoV-2 infection, reported precise metrics of test performance must be questioned. The response to SARS-CoV-2 has delivered considerable diagnostic innovation, but for a technology to be maximised, it must be demonstrably reproducible and fit for purpose. If novel diagnostic solutions for SARS-CoV-2 are to succeed, equally innovative mechanisms are needed to ensure widespread clinical and surveillance application, enabling agreed standards and metrics to ensure comparability.

Although T2-weighted axial magnetic resonance imaging (MRI) has strength in demonstrating morphologic characteristics of the spinal cord in cervical spondylotic myelopathy (CSM), no study has investigated postoperative changes. We aimed to assess postoperative changes on T2-weighted axial MRI using the classification system based on axial imaging in cervical compressive myelopathy (Ax-CCM) and associated impact on outcome in CSM. In total, 250 patients with CSM who underwent decompressive surgery with preoperative and postoperative MRI were included. At first, we investigated the presence of increased signal intensity (SI) in cervical spinal cord on T2-weighted sagittal images. Next, the increased SI was assessed using Ax-CCM on T2weighted axial images. The classifications were type 0, no-signal abnormality; single-level type 1, diffuse; single-level type 2, fuzzy focal; single-level type 3, discrete focal; and two-level. The recovery rates (RRs) of modified Japanese Orthopaedic Association (mJOA) score were evaluated from 5 to 10 months postoperatively. Eighty-seven patients (34.8%) exhibited postoperative changes. Most of postoperative changes were in single-level type 1 and 2. Patterns of changes were resolution, reduced extent, or transition to discrete margin. The most common pattern was resolution in type 1 (23.9%) and transition to discrete margin in type 2 (46.5%). In each group, resolution showed the best RR, but insignificantly (p > 0.05).

Background There are no consensus and guidelines on the optimal interval of repeat epidural steroid injections (ESI) for patients with lumbar herniated intervertebral disc (HIVD) who respond to initial ESI. Purpose To evaluate the effectiveness of ESI in patients with HIVD under a “wait-and-see” policy, i.e. as-needed injections not on a predetermined schedule. Material and Methods A total of 592 patients with lumbar HIVD received spine injections between January and December 2017. After excluding patients with excellent (no pain) or poor (>70% residual symptoms) response in the two- or three-week pain assessment, the data of 141 responders were analyzed (60 men, 73 women; age = 50.55±17.25 years). We divided patients into wait-and-see (n=124) and early repeat-ESI (n=17) groups, who received repeat ESIs within three weeks. Evaluations of characteristics and outcomes were performed with the chi-square test or independent Student’s t-test. Results Six patients (4.8%) in the wait-and-see group and 1 (5.9%) in the early repeat-ESI group underwent operation within one year ( P=0.85). A mean of 1.52±0.82 ESIs was performed in the wait-and-see and a mean of 2.29±0.47 ESIs in the early repeat-ESI group over one year ( PConclusion A “wait-and-see” policy could be an effective pain management option for patients with lumbar HIVD who respond to initial ESI.

BackgroundThe diagnostic accuracy of magnetic resonance imaging (MRI) is low for detecting a subscapularis tendon tear.PurposeTo identify MRI findings that may predict the presence of a clinically significant subscapularis tendon tear requiring surgical repair.Material and MethodsWe reviewed shoulder MR images of patients who had undergone arthroscopic rotator cuff repair at our institution between June 2018 and May 2019. Patients were divided into two groups: the study group (n = 51), with an intermediate- to high-grade partial thickness tear of the subscapularis tendon suspected on preoperative MRI and intermediate or higher grade of the tendon tear proven on arthroscopy; and the control group (n = 18), with an intermediate- to high-grade partial thickness tear of the subscapularis tendon suspected on preoperative MRI but no tear or low-grade partial thickness tear of the tendon shown on arthroscopy. Preoperative MR images were retrospectively evaluated by two readers for the size of the subscapularis tendon tear, bone reactions at the lesser tuberosity, and long head of the biceps tendon (LHBT) pathology.ResultsThe subscapularis tendon tear measured by reader 2 was larger in the study group than in the control group. The prevalence of a tear ( P = 0.006 for reader 1; P = 0.011 for reader 2) and malposition ( P ConclusionA tear and malposition of the LHBT on MR images may predict the presence of a clinically significant subscapularis tendon tear.

It is important to differentiate between benign and malignant myxoid tumors to establish the treatment plan, determine the optimal surgical extent, and plan postoperative surveillance, but differentiation may be complicated by imaging-feature overlap. Texture analysis is used for quantitative assessment of imaging characteristics based on mathematically calculated pixel heterogeneity and has been applied to the discrimination of benign from malignant soft tissue tumors (STTs). In this study, we aimed to assess the diagnostic value of the texture features of conventional magnetic resonance images for the differentiation of benign from malignant myxoid STTs. Magnetic resonance images of 39 patients with histologically confirmed myxoid STTs of the extremities were analyzed. Qualitative features were assessed and compared between the benign and malignant groups. Texture analysis was performed, and texture features were selected based on univariate analysis and Fisher’s coefficient. The diagnostic value of the texture features was assessed using receiver operating curve analysis. T1 heterogeneity showed a statistically significant difference between benign and malignant myxoid STTs, with substantial inter-reader reliability. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of T1 heterogeneity were 55.6%, 83.3%, 88.2%, 45.5%, and 64.1%, respectively. Among the texture features, T2w-WavEnLL_s-3 showed good diagnostic performance, and T2w-WavEnLL_s-4 and GeoW4 showed fair diagnostic performance. The logistic regression model including T1 heterogeneity and T2_WavEnLL_s-4 showed good diagnostic performance. However, there was no statistically significant difference between the overall qualitative assessment by a radiologist and the predictor model. Geometry-based and wavelet-derived texture features from T2-weighted images were significantly different between benign and malignant myxoid STTs. However, the texture features had a limited additive value in differentiating benign from malignant myxoid STTs.

The present study assessed test–retest and inter-observer reliability of diffusion tensor imaging (DTI) in cervical spondylotic myelopathy (CSM), as well as the agreement among measurement methods. A total 34 patients (12 men, 22 women; mean age, 58.7 [range 45–79] years) who underwent surgical decompression for CSM, with pre-operative DTI scans available, were retrospectively enrolled. Four observers independently measured fractional anisotropy (FA) values twice, using three different measurement methods. Test–retest and inter-observer reliability was assessed using intraclass correlation coefficients (ICCs). Overall, inter-observer agreements varied according to spinal cord level and the measurement methods used, and ranged from poor to excellent agreement (ICC = 0.374–0.821), with relatively less agreement for the sagittal region of interest (ROI) method. The radiology resident and neuro-radiologist group showed excellent test–retest reliability at almost every spinal cord level (ICC = 0.887–0.997), but inter-observer agreements varied from fair to good (ICC = 0.404–0.747). Despite excellent test–retest reliability of the ROI measurements, FA measurements in patients with CSM varied widely in terms of inter-observer reliability. Therefore, DTI parameter data should be interpreted carefully when applied clinically.

To evaluate the diagnostic performance and reliability of magnetic resonance of arthrography (MRA) in diagnosis of subscapularis (SSC) tendon tears between two reviewers with varying levels of experience, and compare the results with clinical tests. SSC tendons were retrospectively evaluated in a total of 272 patients with arthroscopic confirmations. A total of 548 shoulder MRAs were evaluated by two musculoskeletal radiologists, and SSC tendon pathologies were classified into three groups: intact tendon (n = 149), partial-thickness tear (n = 92), or full-thickness tear (n = 31). Diagnostic performance was determined using arthroscopy as gold standard and compared with results of four clinical tests. Intra- and inter-observer reliabilities of two reviewers were evaluated using kappa statistics. For full-thickness tears, mean values of sensitivity, specificity, and accuracy of reviewer 1/reviewer 2 were 71.0%/87.1%, 97.3%/98.3%, and 94.4%/95.5%, respectively. For partial-thickness tears, mean values of sensitivity, specificity, and accuracy were 72.8%/73.4%, 78.3%/81.2%, and 76.5%/78.5%, respectively. Intra- and inter-observer reliabilities for both reviewers were good to very good (k = 0.85/0.93, p

In March 2020, the South African government implemented various non-pharmacological prevention and control measures (e.g. isolation, social distancing and quarantine) in response to the COVID-19 pandemic. We summarise evidence from a rapid Cochrane review on the effect of quarantine alone v. quarantine plus combination measures to prevent transmission of and mortality caused by COVID-19. The findings show that when started earlier, quarantine combined with other prevention and control measures can be more effective than quarantine alone, and cost less.

Heavily T2-weighted MR myelography (HT2W-MRM) is emerging as an alternative approach for detection and follow up of CSF leaks. We aimed to assess epidural blood patch (EBP) treatment outcome when using HT2W-MRM as the primary modality for detecting CSF leak and planning EBP placement in routine clinical practice. Since 2018, patients at our institute suspected of having CSF leak, routinely HT2W-MRM instead of CT myelography to determine presence of the leak and identify the EBP target site. Fifty-nine consecutive patients suspected of having a CSF leak underwent HT2W-MRM. After excluding patients with subdural hematoma and poor image quality, 26 (10 men, 16 women; mean age 44.92 ± 12.6 years) patients were included in this study. Patients received EBP on the basis of HT2W-MRM assessments and clinical assessment. Imaging findings and clinical outcome were evaluated. CSF leak was identified in 21 patients (80.8%, 21/26) based HT2W-MRM. Most cases were graded on a confidence scale as CSF leak definitely (n = 13) or probably (n = 3) present. Successful clinical EBP treatment was achieved in 14 of 17 patients (82.4%) after first targeted EBP, and patient symptoms significantly improved after treatment (numerical rating score 6.4 before EBP, 1.3 after EBP, P 0.001). HT2W-MRM based EBP are the rational and effective choices for CSF leak treatment in routine clinical practice.

A social impact bond (SIB) is an innovative financing mechanism to attract investors to social programmes traditionally funded by governments. In this article, in celebration of the 50th anniversary of the South African Medical Research Council (SAMRC), the authors describe the SAMRC's first foray into this new world of financing through a SIB to improve the health and quality of life of adolescent girls and young women (AGYW). The AGYW SIB is in its preparatory phase and is scheduled for implementation in 2020. The authors describe the mechanism, including financial flows and the process of customising the SIB to meet the needs of AGYW, focusing on HIV prevention and treatment and the prevention and management of unintended pregnancies in schoolgoing AGYW. The authors outline an approach to designing the package of interventions, the metrics associated with such a programme and the business model. It is hypothesised that the proposed approach will lead to an improvement in programmatic outcomes, monitoring and evaluation tools and cost-effectiveness, and will develop key learning data for the future use of SIBs in health service delivery.

To identify the findings on magnetic resonance imaging most strongly associated with meniscal ramp lesions in patients with an anterior cruciate ligament tear. Seventy-eight consecutive patients (mean age, 33.7 years; 64 male, 14 female) with an arthroscopically proven anterior cruciate ligament tear were included in this retrospective study. The presence of the following six features on magnetic resonance images were recorded: complete fluid filling between the posterior horn of the medial meniscus and the capsule margin; edema affecting the posterior capsule; irregularity of the medial meniscus at the posterior margin; fluid at the periphery of the medial meniscus; the corner notch sign; and a vertical tear at the medial meniscus. Findings at arthroscopy served as the reference standard. Diagnostic accuracy, sensitivity, and interobserver agreement were calculated. Seven ramp lesions were noted on arthroscopy (9%). Findings of irregularity at the posterior margin (p = 0.001) and complete fluid filling between the posterior horn of the medial meniscus and the capsule margin (p = 0.004) on magnetic resonance imaging were significantly associated with the presence of a ramp lesion. With the irregularity at the posterior margin, sensitivity was 86% and specificity was 79%. Complete fluid filling sign showed sensitivity of 57% and specificity of 92%. Concordance of the two readers for the six magnetic resonance imaging features was fair to very good (k = 0.38–0.91). Irregularity at posterior margin and complete fluid filling were most sensitive findings for detecting of a ramp lesion on magnetic resonance imaging.

EarlyBird and EarlyBird Plus are parent education and training programmes designed by the UK National Autistic Society in 1997 and 2003, having been delivered to more than 27,000 families in 14 countries. These group-based programmes aim to (1) support parents immediately after diagnosis of autism spectrum disorder, (2) empower parents, encouraging a positive perception of their child’s autism spectrum disorder and (3) help parents establish good practice. In the absence of any previous comprehensive review, we performed a scoping review of all peer-reviewed publications on EarlyBird/EarlyBird Plus. A search was conducted between February and June 2016 using EbscoHost, Sabinet, SAGE Journals, Directory of Open Access Journals, BioMed Central, Scopus, ScienceDirect and grey literature. Two reviewers independently screened titles and abstracts for inclusion. In total, 18 articles were identified: 16 from the United Kingdom and 2 from New Zealand. We reviewed the context, study populations, design, outcome measures, whether focus was on parental perception, parental change or child changes and programme feasibility. Strong parental support for the acceptability but lower level evidence of efficacy of EarlyBird/EarlyBird Plus was found. Future research should consider randomised controlled trials. There is no research on EarlyBird/EarlyBird Plus in low-resource settings; therefore, we recommend broader feasibility evaluation of EarlyBird/EarlyBird Plus including accessibility, cultural appropriateness and scalability.

Purpose: Osteoclast activity is an important factor in the pathogenesis of skeletal metastases and is a potential therapeutic target. This study aimed to determine if selective uptake of 99mTc-maraciclatide, a radiopharmaceutical targeting αvβ3 integrin, occurs in prostate cancer (PCa) bone metastases and to observe the changes following systemic therapy. Methods: The study group comprised 17 men with bone-predominant metastatic PCa who underwent whole-body planar and single-photon emission computed tomography/computed tomography (SPECT/CT) imaging with 99mTc-maraciclatide before (n = 17) and 12 weeks after (n = 11) starting treatment with abiraterone. Tumour to normal bone (T:N) ratios, tumour to muscle (T:M) ratios and CT Hounsfield units (HU) were measured in up to five target metastases in each subject. An oncologist blinded to study scans assessed clinical responses up to 24 weeks using conventional criteria. Results: Before treatment, metastases showed specific 99mTc-maraciclatide accumulation (mean planar T:N and T:M ratios 1.43 and 3.06; SPECT T:N and T:M ratios 3.1 and 5.19, respectively). Baseline sclerotic lesions (389–740 HU) showed lower T:M ratios (4.22 vs. 7.04, p = 0.02) than less sclerotic/lytic lesions (46–381 HU). Patients with progressive disease (PD; n = 5) showed increased planar T:N and T:M ratios (0.29 and 12.1%, respectively) and SPECT T:N and T:M ratios (11.9 and 20.2%, respectively). Patients without progression showed decreased planar T:N and T:M ratios (0.27 and −8.0%, p = 1.0 and 0.044, respectively) and SPECT T:N and T:M ratios (−21.9, and −27.2%, p = 0.3 and 0.036, respectively). The percentage change in CT HU was inversely correlated with the percentage change in SPECT T:M ratios (r = −0.59, p = 0.006). Conclusions: 99mTc-maraciclatide accumulates in PCa bone metastases in keeping with increased αvβ3 integrin expression. Greater activity in metastases with lower CT density suggests that uptake is related to osteoclast activity. Changes in planar and SPECT T:M ratios after 12 weeks of treatment differed between patients with and without PD and 99mTc-maraciclatide imaging may be a potential method for assessing early response.

Objective To compare the T1-weighted spectral presaturation with inversion-recovery sequences (T1 SPIR) with T2-weighted turbo spin-echo sequences (T2 TSE) on 3T magnetic resonance arthrography (MRA) in the evaluation of the subscapularis (SSC) tendon tear with arthroscopic findings as the reference standard. Materials and methods This retrospective study included 120 consecutive patients who had undergone MRA within 3 months between April and December 2015. Two musculoskeletal radiologists blinded to the arthroscopic results evaluated T1 SPIR and T2 TSE images in separate sessions for the integrity of the SSC tendon, examining normal/articular-surface partial-thickness tear (PTTa)/full-thickness tear (FTT). Diagnostic performance of T1 SPIR and T2 TSE was calculated with arthroscopic results as the reference standard, and sensitivity, specificity, and accuracy were compared using the McNemar test. Interobserver agreement was measured with kappa (κ) statistics. Results There were 74 SSC tendon tears (36 PTTa and 38 FTT) confirmed by arthroscopy. Significant differences were found in the sensitivity and accuracy between T1 SPIR and T2 TSE using the McNemar test, with respective rates of 95.9-94.6% vs. 71.6-75.7% and 90.8-91.7% vs. 79.2-83.3% for detecting tear; 55.3% vs. 31.6-34.2% and 85.8% vs. 78.3-79.2%, respectively, for FTT; and 91.7-97.2% vs. 58.3-61.1% and 89% vs. 78-79.3%, respectively, for PTTa. Interobserver agreement for T1 SPIR was almost perfect for T1 SPIR (κ = 0.839) and substantial for T2 TSE (κ = 0.769). Conclusion T1-weighted spectral presaturation with inversion-recovery sequences is more sensitive and accurate compared to T2 TSE in detecting SSC tendon tear on 3T MRA.

Highlights • Talaromyces marneffei infections are common in immunocompromised patients from East Asia. • Blastomyces and Histoplasma antigen tests have been shown to have cross reactivity between one another and other infections. • SIADH has been shown to be caused by certain opportunistic lung infections in the absence of CNS insults., Talaromyces marneffei is a fungal opportunistic infection usually seen in immunocompromised patients from eastern countries. In the US when examining HIV-patients for suspected fungal infections, laboratory serological tests guide therapy until cultures are available. We present the case of a 35-year-old HIV patient originally from Thailand in which urine lab results were positive for Blastomyces and Histoplasma antigen, but biopsy showed T. marneffei. Concomitantly the patient presented with hyponatremia which was deemed to be from SIADH. We present the first case of a patient with T. marneffei cross reactivity with Blastomyces, Histoplasma and SIADH due to pulmonary disease.

Study design Case series study. Objective The aim was to investigate the incidence of retro-odontoid pseudotumor in patients with atlantoaxial instability (AAI) and evaluate pseudotumor regression after posterior fixation. Summary of background data The incidence of retro-odontoid pseudotumor in atlantoaxial instability patients remains uncertain. Moreover, the regression of retro-odontoid pseudotumor after posterior fixation in patients with various underlying diseases needs to be further investigated. Methods From July 2004 to August 2015, 175 patients with AAI underwent posterior fixation operations at our institution. After excluding 11 patients (previous operation, n = 4; history of tumor, n = 7), the final study population comprised 164 patients. The final study population was categorized according to their underlying diseases (rheumatoid arthritis [RA], os odontoideum, atlanto-occipital assimilation, dens fracture, AAI of unknown cause, etc.) and age (adult and pediatric groups). The incidence of retro-odontoid pseudotumor in each group was analyzed. Pre- and postoperative magnetic resonance or computed tomography images were reviewed to assess its regression following surgery. Results Of the 164 patients included, 38 had retro-odontoid pseudotumor (23.2%). Three were diagnosed with RA and the rest were non-RA patients including os odontoideum (n = 12), dens fracture (n = 6), atlanto-occipital assimilation (n = 4), Morquio syndrome (n = 1), and AAI of unknown cause (n = 12). Pseudotumor size regressed in all 38 patients after atlantoaxial posterior fixation. There was a statistically significant decrease in pseudotumor size (the length between the anterior border of the odontoid process to the posterior border of the pseudotumor) from a mean length of 17.7 to 14.9 mm (P Conclusions The patients had various underlying diseases and the overall incidence of retro-odontoid pseudotumor in patients with symptomatic AAI was 23.2% at our institution during the past 11 years. All patients who underwent posterior fixation for AAI showed a statistically significant decrease in pseudotumor size. Level of evidence 4.

Human mitochondrial transcription factor A (TFAM) has been implicated in promoting tumor growth and invasion. TFAM activates mitochondrial DNA (mtDNA) transcription, and affects nuclear gene expression through mitochondrial retrograde signaling. In this study, we investigated the effects of TFAM depletion on the morphology and transcriptome of MKN45 gastric cancer cells. Morphology alteration became visible at 12 h after TFAM knockdown: the proportion of growth-arrested polygonal cells versus oval-shaped cells increased, reaching a half-maximum at 24 h and a near-maximum at 36 h. TFAM knockdown upregulated four genes and downregulated six genes by more than threefold at 24 h and similarly at 48 h. Among them, the knockdown of CFAP65 (cilia and flagella associated protein 65) or PCK1 (cytoplasmic phosphoenolpyruvate carboxykinase) rescued the effects of TFAM depletion on cell morphology and proliferation. PCK1 was found to act downstream of CFAP65 in calcium-mediated retrograde signaling. Furthermore, mtDNA depletion by 2′,3′-dideoxycytidine was sufficient for induction of CFAP65 and PCK1 expression and inhibition of cell proliferation, but oxidative phosphorylation blockade or mitochondrial membrane potential depolarization was not. Thus, the TFAM–mtDNA–calcium–CFAP65–PCK1 axis participates in mitochondrial retrograde signaling, affecting tumor cell differentiation and proliferation.

The objective of this study is to evaluate the effect of the metal artifact reduction algorithm for orthopedic implants (O-MAR) on CT image quality for patients with reverse total shoulder arthroplasty (RTSA), with emphasis placed on the evaluation of bone in the vicinity of prostheses.Sixty-five patients who underwent CT scanning after RTSA were enrolled in the study. Two radiologists analyzed the images reconstructed with filtered back projection (FBP) with or without O-MAR processing. Images were evaluated to determine the degree of streaking artifacts, the confidence in depicting various structures around the prosthesis, and the presence of pseudolesions. The mean CT number and SD of the selected ROIs placed in the greater tuberosity, glenoid bone, and deltoid muscle were recorded. For measurements from the greater tuberosity and glenoid bone, the frequency with which the measurement met the typical CT number of bone was calculated.O-MAR images showed less metal streak artifact and noise and provided better visualization of the axillary neurovascular bundle compared with FBP images, with a statistically significant difference (p0.001 for all). FBP images were found to be statistically significantly better than O-MAR images, offering better visualization of bone cortex, bone trabeculae, and the bone-prosthesis interface (p0.001 for all). Scapular pseudonotching was observed on 4.6% of FBP images and 36.9% of O-MAR images. The pseudocemented appearance was noted on 47.7% of O-MAR images but was not seen on FBP images.The use of O-MAR improved CT image quality for patients with RTSA in the aspect of metal artifact reduction and soft-tissue profile. However, O-MAR tends to degrade depiction of the bone trabeculae and bone cortex and generate new artifacts, including a pseudocemented appearance and scapular pseudonotching.

To evaluate the diagnostic value of MR arthrography (MRA) in diagnosing instability of the LHBT in patients with rotator cuff tendon tear. The MR arthrograms of 101 patients were retrospectively reviewed and correlated with arthroscopic findings as the standard reference. Images were evaluated for (1) the integrity of the LHBT, (2) the position of the LHBT (subluxation/dislocation on axial images, inferior displacement on oblique sagittal image) and (3) the integrity of the biceps pulley (SGHL, supraspinatus and subscapularis tendon adjacent to the rotator interval). The integrity of the LHBT was correctly classified in 74.3% (75/101) and 66.3% (67/101) by readers 1 and 2, respectively. The diagnosis of LHBT instability could be made on axial images with a sensitivity of 82.6% and 73.9% and specificity of 69.9% and 87.7%, whereas the displacement sign on sagittal images had a sensitivity of 73.9% and 78.3% and a specificity of 64.4% and 61.6%, respectively. Assessing the integrity of the SGHL had a sensitivity of 60.9 and 93.3% and a specificity of 70.4 and 75.0%, respectively. By combining the different image findings, the accuracy in assessing LHBT instability was 80.9 and 90.5% with a sensitivity of 60.9 and 86.7% and specificity of 83.1 and 91.8%, respectively. Individual image findings may have a limited role in diagnosing LHBT instability in patients with rotator cuff tendon tear. The accuracy of MRA may be improved by assessing the integrity of the biceps pulley structures along with the position of the LHBT on both axial and sagittal images.

To compare three approaches via the anterior and posterior glenohumeral joints, and the rotator interval in fluoroscopy-guided shoulder arthrography according to the experience of the practitioners. This prospective randomized study was originally designed to have 34 subjects for each approach, and finally evaluated 98 patients (mean age: 51.5 years; 55 men) from July to December 2014, who had shoulder arthrography via the anterior (n = 41) or posterior glenohumeral joint (n = 27) approaches, or via the rotator interval approach (n = 30) by residents (n=76) or fellows (n=22). The success rate, number of punctures, fluoroscopy time, radiation dose, and complications of the three methods were compared, and according to the practitioners. The success rate was 100% for the anterior glenohumeral joint approach (34 out of 34), 90.0% for the posterior glenohumeral joint approach (23 out of 30), and 88.2% for the rotator interval approach (30 out of 34; p = 0.013). There was no difference in the success rate according to the practitioners’ experience. Fluoroscopy time was longest for the posterior glenohumeral joint approach (mean: 95.44 s) and shortest for the rotator interval approach (mean: 31.57 s, p = 0.006). Radiation dose was larger by 1st- or 2nd-year residents (p = 0.014), with no difference among the three approaches. Only one patient who underwent arthrography using the posterior glenohumeral joint approach complained about post-procedural pain. Fluoroscopy-guided shoulder arthrography via the posterior glenohumeral joint or rotator interval approach may be difficult for trainees, and the posterior glenohumeral joint approach may need a long fluoroscopy time.

Advances in imaging and the development of injection techniques have enabled spinal intervention to become an important tool in managing chronic spinal pain. Epidural steroid injection (ESI) is one of the most widely used spinal interventions; it directly delivers drugs into the epidural space to relieve pain originating from degenerative spine disorders-central canal stenoses and neural foraminal stenoses-or disk herniations. Knowledge of the normal anatomy of the epidural space is essential to perform an effective and safe ESI and to recognize possible complications. Although computed tomographic (CT) or combined CT-fluoroscopic guidance has been increasingly used in ESI, conventional fluoroscopic guidance is generally performed. In ESI, drugs are delivered into the epidural space by interlaminar or transforaminal routes in the cervical spine or by interlaminar, transforaminal, or caudal routes in the lumbar spine. Epidurography is usually performed before drug delivery to verify the proper position of the needle in the epidural space. A small amount of contrast agent is injected with fluoroscopic guidance. Familiarity with the findings on a typical "true" epidurogram (demonstrating correct needle placement in the epidural space) permits proper performance of ESI. Findings on "false" epidurograms (demonstrating incorrect needle placement) include muscular staining and evidence of intravascular injection, inadvertent facet joint injection, dural puncture, subdural injection, and intraneural or intradiscal injection. ©RSNA, 2016 An earlier incorrect version of this article appeared online. This article was corrected on December 22, 2016.

Aims.This study evaluated the psychometric properties of the Strengths and Difficulties Questionnaire Self-Report (SDQ-S) in South African adolescents, and compared findings with data from the UK, Australia and China.Methods.A sample of 3451 South African adolescents in grade 8, the first year of secondary school (Mage = 13.7 years), completed the SDQ-S in Afrikaans, English or isiXhosa. Means, group differences and internal consistency were analysed using SPSS V22, and confirmatory factor analyses were conducted using MPlus V7.Results.In the South African sample, significant gender differences were found for four of the five sub-scale means and for total difficulties, but gender differences of alpha scores were negligible. The internal consistency for the total difficulties, prosocial behaviour and emotional symptoms sub-scales were fair. UK cut-off values for caseness (set to identify the top 10% of scores in a UK sample) led to a higher proportion of South African adolescents classified in the ‘abnormal’ range on emotional and peer difficulties and a lower proportion classified in the ‘abnormal’ range for hyperactivity. South African cut-offs were therefore generated. The cross-country comparison with UK, Australian and Chinese data showed that South African adolescent boys and girls had the highest mean scores on total difficulties as well as on the subscales of emotional symptoms and conduct problems. In contrast, South African boys and girls had the lowest mean scores for hyperactivity/inattention. The UK boys and girls had the highest mean scores for hyperactivity/inattention, while the Australian sample had the highest scores for prosocial behaviours. The Chinese boys had the highest peer problem mean scores and Chinese boys and girls had the lowest means on prosocial behaviours. Confirmatory factor analyses showed significant item loadings with loadings higher than 0.40 for the emotional and prosocial behaviour sub-scales on the five-factor model, but not for all relevant items on the other three domains.Conclusions.Findings support the potential usefulness of the SDQ-S in a South African setting, but suggest that the SDQ-S should not be used with UK cut-off values, and indicate the need for further validation and standardisation work in South African adolescents. We recommend that in-country cut-offs for ‘caseness’ should be used for clinical purposes in South Africa, that cross-country comparisons should be made with caution, and that further examination of naturalistic clusters and factors of the SDQ should be performed in culturally and contextually diverse settings.

To develop a deep learning algorithm that can rule out significant rotator cuff tear based on conventional shoulder radiographs in patients suspected of rotator cuff tear. The algorithm was developed using 6793 shoulder radiograph series performed between January 2015 and June 2018, which were labeled based on ultrasound or MRI conducted within 90 days, and clinical information (age, sex, dominant side, history of trauma, degree of pain). The output was the probability of significant rotator cuff tear (supraspinatus/infraspinatus complex tear with > 50% of tendon thickness). An operating point corresponding to sensitivity of 98% was set to achieve high negative predictive value (NPV) and low negative likelihood ratio (LR−). The performance of the algorithm was tested with 1095 radiograph series performed between July and December 2018. Subgroup analysis using Fisher’s exact test was performed to identify factors (clinical information, radiography vendor, advanced imaging modality) associated with negative test results and NPV. Sensitivity, NPV, and LR− were 97.3%, 96.6%, and 0.06, respectively. The deep learning algorithm could rule out significant rotator cuff tear in about 30% of patients suspected of rotator cuff tear. The subgroup analysis showed that age

Objective: Using a social ecological framework, this study aimed to establish emerging mental health clinicians and researchers' perspectives about child and adolescent mental health (CAMH) in Africa. Method: Perspectives of 17 participants from Ethiopia, Kenya, South Africa, Tunisia, Uganda and Zambia, whose professional backgrounds ranged from psychiatry to speech-language therapy, were collected at an African CAMH conference. Data were gathered using open-ended questions, using an online survey. Data were analysed using theoretical thematic analysis. Results: An adapted social ecological framework highlighted: An increased need for commitment from governments to improve CAMH in Africa; and addressing mental health stigma and discrimination through community awareness. The need for specialised CAMH facilities were identified, particularly in the public health sector. The need for multi-sectoral, multi-disciplinary partnerships for advocacy, service delivery, and continuity of care were also identified. Participants emphasised the importance of CAMH awareness, and the role of governments in recognising CAMH needs and using policies to improve CAMH in Africa. Participants were hopeful about the transformation of CAMH on the continent. Conclusion: The participants prioritised government- and community-level awareness to increase the resources and support offered by CAMH services in Africa.

While bone has the capability to heal itself, there is a great difficulty in reconstituting large bone defects created by heavy trauma or the resection of malignant tumors. Also, osteonecrosis of the femoral head (ONFH), which is caused by obstruction of the blood supply to bone cells and occurs in the young, is not amenable for successful bone regeneration. We developed VEGF- and BMP2-transfected adipose stem cells (ASCs) using electroporation that can effectively treat bone defects by providing rapid angiogenesis and osteogenesis. The optimal ratio of BMP2- to VEGF-transfected ASCs to enhance both osteogenesis and angiogenesis was 9 : 1. BMP2-/VEGF-transfected ASCs administered in this ratio effectively healed critical-size calvarial defects and long-bone segmental defects in immunosuppressed rats. The implanted cells did not migrate out of the implantation site by the 56th day. TAZ, TEAD, and ANKRD1 were overexpressed in BMP2-/VEGF-transfected ASCs, possibly proposing the mechanism of enhanced bone regeneration and angiogenesis. Our results suggest the possibility of using gene–cell therapy that can induce rapid angiogenesis and osteogenesis in inhospitable avascular environments including large bone defects and ONFH.

BackgroundAlthough both 1.5-Tesla (T) and 3-T magnetic resonance imaging (MRI) are widely used for the diagnosis of cervical spondylotic myelopathy (CSM), there have been no comparative studies.Pur...

RNF20/40 E3 ubiquitin ligase-mediated histone H2B monoubiquitylation plays important roles in many cellular processes, including transcriptional regulation. However, the multiple defects observed in RNF20-depleted cells suggest additional ubiquitylation targets of RNF20/40 beyond histone H2B. Here, using biochemically defined assays employing purified factors and cell-based analyses, we demonstrate that RNF20/40, in conjunction with its cognate E2 ubiquitin-conjugating enzyme RAD6, monoubiquitylates lysine 381 of eEF1BδL, a heat shock transcription factor. Notably, monoubiquitylation of eEF1BδL increases eEF1BδL accumulation and potentiates recruitment of p-TEFb to the promoter regions of heat shock-responsive genes, leading to enhanced transcription of these genes. We further demonstrate that cooperative physical interactions among eEF1BδL, RNF20/40, and HSF1 synergistically promote expression of heat shock-responsive genes. In addition to identifying eEF1BδL as a novel ubiquitylation target of RNF20/40 and elucidating its function, we provide a molecular mechanism for the cooperative function of distinct transcription factors in heat shock-responsive gene transcription.

BackgroundBoth multidetector computed tomography (MDCT) and magnetic resonance imaging (MRI) are used for assessment of lumbar foraminal stenosis (LFS). Therefore, it is relevant to assess agreement between these imaging modalities.PurposeTo determine intermodality, inter-, and intra-observer agreement for assessment of LFS on MDCT and MRI.Material and MethodsA total of 120 foramina in 20 patients who visited our institution in January and February 2014 were evaluated by six radiologists with different levels of experience. Radiologists evaluated presence and severity of LFS on sagittal CT and MR images according to a previously published LFS grading system. Intermodality agreement was analyzed by using weighted kappa statistics, while inter- and intra-observer agreement were analyzed by using intraclass correlation coefficients (ICCs) and kappa statistics.ResultsOverall intermodality agreement was moderate to good (kappa, 0.478–0.765). In particular, two professors and one fellow tended to overestimate the degree of LFS on CT compared with MRI. For inter-observer agreement of all six observers, ICCs indicated excellent agreement for both CT (0.774) and MRI (0.771), while Fleiss’ kappa values showed moderate agreement for CT (0.482) and MRI (0.575). There was better agreement between professors and fellows compared with residents. For intra-observer agreement, ICCs indicated excellent agreement, while kappa values showed good to excellent agreement for both CT and MRI.ConclusionMDCT was comparable to MRI for diagnosis and assessment of LFS, especially for experienced observers. However, there was a tendency to overestimate the degree of LFS on MDCT compared with MRI.

Sexual and reproductive health (SRH) services for adolescent girls and young women (AGYW) remain inadequate - both globally and in South Africa (SA). We systematically scoped the available policies and guidelines for SRH-related policy for AGYW in SA. We found many available policies and guidelines to address issues of family planning, HIV prevention and care and antenatal and maternal care. Despite the wealth of guidance, SA's high rates of pregnancy and HIV transmission continue unabated. Our policy review and analysis identified issues for researchers and policymakers to consider when developing and implementing programmes to improve SRH services. We suggest that considering national policies alongside evidence of what is effective, as well as contextual barriers to and enablers of strategies to address AGYW needs for SRH, are among the key steps to addressing the policy-to-implementation gap.

Objective To assess the learnability of two magnetic resonance imaging (MRI) grading systems for lumbar central canal stenosis based on inter-observer agreement and test-retest reliability of doctors with no prior knowledge of the two systems. Materials and methods Two clinical fellows, one novice radiology resident, one neurosurgeon, and one orthopedic surgeon, who were unaware of the two qualitative MRI grading systems prior to this study, acquainted themselves with the teaching files. All five observers independently assessed the LCCS grade of 70 patients using T2-weighted axial magnetic resonance images at the L2-3, L3-4, L3-4, and L5-S1 disc levels. Analysis was performed twice at an interval of two months. Results The inter-observer agreement among all five readers was excellent and test-retest reliability was moderate to excellent for both the Schizas and Lee systems. Positive percentage agreements were found to be over 0.8 in almost all observers with relatively narrow 95% confidence limits. Conclusion Both Schizas and Lee MRI grading systems for LCCS are reliable grading systems, and can be used as a learnable method for both clinicians and radiologists.

Purpose To explore the feasibility of postoperative high-tesla DTI in CSM and optimize its acquisition parameters using both single-shot (SS) echo-planar imaging (EPI) and multi-shot (MS) EPI, and to evaluate correlation between image degradation and operative methods. Method We enrolled twenty-seven patients with CSM scheduled for MRI at one month after cervical operations who were divided into three groups; 11 patients in group 1; 11 in group 2; and 5 in group 3. The patient in each group underwent two sets of DTI using both SS-EPI and MS-EPI with different diffusion gradient directions. Qualitative and quantitative analysis of fractional anisotropy (FA) and color-coding maps were performed to evaluate image distortion and spinal cord visualization and were compared between SS- and MS-EPI. DTI indices, including the number of reconstructed fibers, mean apparent diffusion coefficient (ADC) values, and mean FA values, were acquired. Results In the metallic segment, MS-EPI with 6 diffusion gradients showed significantly less distortion and better cord visualization than SS-EPI. Fiber tracking was also superior with MS-EPI sequences. Scores in the subjective motor improvement scale showed a moderately positive correlation correlated only with the mean ADC at 1 month postoperatively. Regarding the operation methods, DTI in patients who underwent anterior cervical discectomy and fusion showed the least image distortion and 100 % success rate of fiber tractography. Conclusions Compared with SS-EPI, MS-EPI with motion correction significantly improves image distortions and increases the success rate of fiber tractography in CSM patients with metal implants.