The view of Hong Kong parents on secondary use of dried blood spots in newborn screening program.

BACKGROUND: Residual dried blood spots (rDBS) from newborn screening programmes represent a valuable resource for medical research, from basic sciences, through clinical to public health. In Hong Kong, there is no legislation for biobanking. Parents' view on the retention and use of residual newborn blood samples could be cultural-specific and is important to consider for biobanking of rDBS. OBJECTIVE: To study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents. METHODS: A mixed-method approach was used to study the views and concerns on long-term storage and secondary use of rDBS from newborn screening programmes among Hong Kong Chinese parents of children 0-3 years or expecting parents through focus groups (8 groups; 33 participants) and a survey (n = 1012, 85% mothers) designed with insights obtained from the focus groups. We used framework analysis to summarise the themes as supportive factors, concerns and critical arguments for retention and secondary use of rDBS from focus group discussion. We used multiple logistic regression to assess factors associated with support for retention and secondary use of rDBS in the survey. RESULTS: Both in focus groups and survey, majority of parents were not aware of the potential secondary use of rDBS. Overall secondary use of rDBS in medical research was well accepted by a large proportion of Hong Kong parents, even if all potential future research could not be specified in a broad consent. However parents were concerned about potential risks of biobanking rDBS including leaking of data and mis-use of genetic information. Parents wanted to be asked for permission before rDBS are stored and mainly did not accept an "opt-out" approach. The survey showed that parents born in mainland China, compared to Hong Kong born parents, had lower awareness of newborn screening but higher support in biobanking rDBS. Higher education was associated with support in rDBS biobanking only among fathers. CONCLUSION: Long-term storage and secondary use of rDBS from newborn screening for biomedical research and a broad consent for biobanking of rDBS are generally acceptable to Hong Kong parents given their autonomy is respected and their privacy is protected, highlighting the importance of an accountable governance and a transparent access policy for rDBS biobanks.

Surprise on Popping the Popliteal Swelling: A Case Report.

Popliteal swelling is a common complaint seen in the practice of orthopaedics. Although imaging is useful to aid in the diagnosis of popliteal swelling pre-operatively, definitive diagnosis is often obtained post-operatively through histopathological report of the swelling. Baker's cyst arises medially and hence usually spares the posterolaterally located neurovascular bundle until it becomes larger in size. A thrombosed aneurysm can mimic that of Baker's cyst on computed tomography (CT) imaging in view of its location and the absence of contrast within the lesion. Diagnosis of a popliteal swelling with neural or vascular compression is not as straightforward and surgeons should be well aware that intra-operative findings may differ from diagnosis made pre-operatively. Meticulous exploration is pertinent in identifying the origin of the swelling and structures related to it. MRI imaging of the swelling should be done pre-operatively whenever possible.

Breeding oat for resistance to the crown rust pathogen Puccinia coronata f. sp. avenae: achievements and prospects.

Crown rust, caused by Puccinia coronata f. sp. avenae (Pca), is a significant impediment to global oat production. Some 98 alleles at 92 loci conferring resistance to Pca in Avena have been designated; however, allelic relationships and chromosomal locations of many of these are unknown. Long-term monitoring of Pca in Australia, North America and elsewhere has shown that it is highly variable even in the absence of sexual recombination, likely due to large pathogen populations that cycle between wild oat communities and oat crops. Efforts to develop cultivars with genetic resistance to Pca began in the 1950s. Based almost solely on all all-stage resistance, this has had temporary benefits but very limited success. The inability to eradicate wild oats, and their common occurrence in many oat growing regions, means that future strategies to control Pca must be based on the assumption of a large and variable prevailing pathogen population with high evolutionary potential, even if cultivars with durable resistance are deployed and grown widely. The presence of minor gene, additive APR to Pca in hexaploid oat germplasm opens the possibility of pyramiding several such genes to give high levels of resistance. The recent availability of reference genomes for diploid and hexaploid oat will undoubtedly accelerate efforts to discover, characterise and develop high throughput diagnostic markers to introgress and pyramid resistance to Pca in high yielding adapted oat germplasm.

Biomechanical analysis of progressive rotator cuff tendon tears on superior stability of the shoulder.

BACKGROUND: The biomechanical relationship between irreparable rotator cuff tear size and glenohumeral joint stability in the setting of superiorly directed forces has not been characterized. The purpose of this study was to quantify kinematic alterations of the glenohumeral joint in response to superiorly directed forces in a progressive posterosuperior rotator cuff tear model. METHODS: Nine fresh-frozen cadaveric shoulders (mean age; 58 years) were tested with a custom shoulder testing system. Three conditions were tested: intact, stage II (supraspinatus) tear, stage III (supraspinatus + anterior half of infraspinatus) tear. At each condition, range of motion and humeral head positions were measured with a "balanced" loading condition, and with a superiorly directed force ("unbalanced loading condition"). At each of the 0°, 20°, and 40° of glenohumeral abduction positions, all measurements were made at 0°, 30°, 60°, and 90° of external rotation (ER). Two-way repeated measures analysis of variance with Tukey post hoc tests were performed for statistical analyses. RESULTS: With the balanced load, no significant change in superior humeral head position was observed in stage II tears. Stage III tears significantly changed the humeral head position superiorly at 30° and 60° ER at each abduction angle compared with the intact condition (P ≤ .028). With superiorly directed load, stage II and stage III tears both showed statistically significant increases in superior translation at all degrees of ER for all degrees of abduction (P ≤ .035), except stage II tears at 0° ER and 40° abduction (P = .185) compared with the intact condition. Stage II tears showed posterior translations with 30° and 60° ER, both at 20° and 40° of abduction. Stage III tears also showed posterior translations with 90° ER for all abduction angles (P ≤ .039). CONCLUSION: With superiorly directed loads, complete supraspinatus tendon tears created superior translations at all abduction angles, and posterior instability in the middle ranges of rotation for 20° and 40° of abduction. Larger tears involving the anterior half of the infraspinatus tendon caused significant superior and posterior translations within the middle ranges of ER for all abduction angles. In addition to superior instability, posterior translation should be considered when selecting or developing surgical techniques for large posterosuperior rotator cuff tears.

Liver damage favors the eliminations of HBV integration and clonal hepatocytes in chronic hepatitis B.

BACKGROUND: HBV integration is suspected to be an obstinate risk factor for hepatocellular carcinoma (HCC) in the era of antiviral therapy. Integration events start to occur in the immunotolerance phase, but their fates in the immune clearance phase have not yet been clarified. Here, we report the influences of liver damage on HBV integration and clonal hepatocyte expansion in patients with chronic hepatitis B (CHB). METHODS: HBV integration breakpoints in liver biopsy samples from 54 CHB patients were detected using a modified next-generation sequencing assay. RESULTS: A total of 3729 (69 per sample) integration breakpoints were found in the human genome, including some hotspot genes and KEGG pathways, especially in patients with abnormal transaminases. The number of breakpoint types, an integration risk parameter, was negatively correlated with HBV DNA load and transaminase levels. The average, maximum and total frequencies of given breakpoint types, parameters of clonal hepatocyte expansion, were negatively correlated with HBV DNA load, transaminase levels and liver inflammation activity grade score. The HBV DNA load and inflammation activity grade score were further found to be positively correlated with transaminase levels. Moreover, nucleos(t)ide analog (NUC) treatment that normalized transaminases nonsignificantly reduced the types, but significantly increased the average frequency and negated the enrichments of integration breakpoints. CONCLUSION: Liver damage mainly removed the inventories of viral integration and clonal hepatocytes in CHB. NUC treatment may have reduced HBV integration but clearly increased clonal hepatocyte expansion, which may explain why HCC risk cannot be ruled out by NUC treatment.

A rare penetrating injury through the axilla caused by stilt pole in a Bajau Laut boy.

An 8-year-old child of Bajau Laut descent (a stateless tribe in Eastern Borneo and the Sulu archipelago) presented following a fall, with penetrating injury through the axilla caused by a stilt pole, exiting at the supero-anterior aspect of the left shoulder. Due to the lack of comprehension of modern medical treatment and poor language skills, the parents refused to consent for detailed radioimaging studies, nor surgical removal and exploration in the operating theatre. The removal of retained stilt pole was done in casualty area in Hospital Tawau, followed by local exploration under sedation and local analgesia. Despite the horrific injury, there was no limb-threatening neurovascular injury sustained. Management of such injury in the nomadic Bajau Laut population provides valuable insight and about the challenges and decisions of management.

EGF receptor inhibitors comprehensively suppress hepatitis B virus by downregulation of STAT3 phosphorylation.

Current antiviral therapy can not cure chronic hepatitis B virus (HBV) infection or eliminate the risk of hepatocellular carcinoma. The licensed epidermal growth factor receptor (EGFR) inhibitors have found to inhibit hepatitis C virus replication via downregulation of signal transducers and activators of transcription 3 (STAT3) phosphorylation. Since STAT3 is also involved in HBV replication, we further studied the anti-HBV efficacy of the EGFR inhibitors in this study. HBV-transfected HepG2.2.15 cells and HBV-infected HepG2-NTCP cells were used as cell models, and HBV replication, the syntheses of viral antigens and the magnitude of the covalently closed circular DNA (cccDNA) reservoir were used as indictors to test the anti-HBV effects of EGFR inhibitors erlotinib and gefitinib. Erlotinib inhibited HBV replication with a half-maximal inhibitory concentration of 1.05 µM. It also reduced the syntheses of viral antigens at concentrations of 2.5 µM or higher. The underlying mechanism was possibly correlated with its inhibition on STAT3 phosphorylation via up-regulation of suppressor of cytokine signaling 3. Gefitinib also inhibited HBV replication and antigen syntheses. Compared with the commonest antiviral drug entecavir, these EGFR inhibitors additionally reduced hepatitis B e antigen and erlotinib also marginally affected the cccDNA reservoir in HBV-infected HepG2-NTCP cells. Interestingly, these promising anti-HBV effects were significantly enhanced by extension of treatment duration. In conclusion, EGFR inhibitors demonstrated a comprehensive anti-HBV potential, highlighting a new strategy to cure HBV infection and suggesting animal model-related studies or clinical try in the future.

Contrast-enhanced swallow study sensitivity for detecting esophagojejunostomy leakage. / Sensibilidad del trago de contraste hidrosoluble para la detección de fugas de anastomosis esofagoyeyunal.

INTRODUCTION AND AIM: Sixty percent of the patients with gastric carcinomas are candidates for surgical resection through total gastrectomy and esophagojejunostomy, the latter of which is associated with leaks in up to 12.3% of cases. There is no standardized procedure for diagnosing anastomotic leaks. The aim of the present study was to establish the diagnostic sensitivity of the contrast-enhanced swallow study for detecting esophagojejunostomy leakage after total gastrectomy. MATERIALS AND METHODS: A retrospective analysis was conducted on patients that underwent total gastrectomy due to gastric adenocarcinoma, within the time frame of 2002 and 2017. Demographic, clinical, and laboratory factors were identified, emphasizing the clinical and radiologic detection of anastomotic leaks. Descriptive statistics were carried out and the sensitivity of the contrast-enhanced swallow study for diagnosing leakage was calculated. RESULTS: Fifty-eight patients were included in the study. Their mean age was 61.5 years. A total of 55.2% of the patients were men and 44.8% were women. Gastric adenocarcinoma was the indication for gastrectomy in 100% of the cases. Anastomotic leak presented in 31.01% of the patients. Diagnostic sensitivity of the contrast-enhanced swallow study for detecting leaks was 66%. CONCLUSIONS: According to our analysis, the contrast-enhanced swallow study had limited diagnostic efficiency for detecting anastomotic leaks, with a sensitivity of 66%. We suggest maintaining high diagnostic suspicion in patients with studies that are initially negative and basing decisions on a more extensive approach.

An artificial intelligence algorithm that differentiates anterior ethmoidal artery location on sinus computed tomography scans.

OBJECTIVE: Deep learning using convolutional neural networks represents a form of artificial intelligence where computers recognise patterns and make predictions based upon provided datasets. This study aimed to determine if a convolutional neural network could be trained to differentiate the location of the anterior ethmoidal artery as either adhered to the skull base or within a bone 'mesentery' on sinus computed tomography scans. METHODS: Coronal sinus computed tomography scans were reviewed by two otolaryngology residents for anterior ethmoidal artery location and used as data for the Google Inception-V3 convolutional neural network base. The classification layer of Inception-V3 was retrained in Python (programming language software) using a transfer learning method to interpret the computed tomography images. RESULTS: A total of 675 images from 388 patients were used to train the convolutional neural network. A further 197 unique images were used to test the algorithm; this yielded a total accuracy of 82.7 per cent (95 per cent confidence interval = 77.7-87.8), kappa statistic of 0.62 and area under the curve of 0.86. CONCLUSION: Convolutional neural networks demonstrate promise in identifying clinically important structures in functional endoscopic sinus surgery, such as anterior ethmoidal artery location on pre-operative sinus computed tomography.

Redox regulation of tyrosine kinase signalling: more than meets the eye.

Protein kinases are essential mediators of cellular signal transduction and are often dysregulated in disease. Among these, protein tyrosine kinases (PTKs) have received specific interest due to their common roles in various diseases including cancer, and emerging observations indicating that PTK signalling pathways are susceptible to regulation by reactive oxygen species (ROS), which are also frequently implicated in disease pathology. While it is well recognized that ROS can impact on tyrosine kinase signalling by inhibiting tyrosine phosphatases, more recent studies highlight additional modes of redox-based regulation of tyrosine kinase signalling by direct redox modification of non-catalytic cysteines within tyrosine kinases or other protein components of this signalling pathway. In this review, we will present recent advancements with respect to redox-based mechanisms in regulating PTK signalling, with a specific focus on recent studies demonstrating direct redox regulation of Src-family kinases and epidermal growth factor receptor kinases. Importantly, redox-based modulation of tyrosine kinases may be relevant for many other kinases and has implications for current approaches to develop pharmacological inhibitors for these proteins.

SIRT5 stabilizes mitochondrial glutaminase and supports breast cancer tumorigenesis.

The mitochondrial enzyme glutaminase (GLS) is frequently up-regulated during tumorigenesis and is being evaluated as a target for cancer therapy. GLS catalyzes the hydrolysis of glutamine to glutamate, which then supplies diverse metabolic pathways with carbon and/or nitrogen. Here, we report that SIRT5, a mitochondrial NAD+-dependent lysine deacylase, plays a key role in stabilizing GLS. In transformed cells, SIRT5 regulates glutamine metabolism by desuccinylating GLS and thereby protecting it from ubiquitin-mediated degradation. Moreover, we show that SIRT5 is up-regulated during cellular transformation and supports proliferation and tumorigenesis. Elevated SIRT5 expression in human breast tumors correlates with poor patient prognosis. These findings reveal a mechanism for increasing GLS expression in cancer cells and establish a role for SIRT5 in metabolic reprogramming and mammary tumorigenesis.

Socioecological differences in factors associated with inconsistent condom use with female sex workers and casual partners: an observational study of heterosexual men attending an anonymous HIV testing clinic in Singapore.

Sexual practices among heterosexual men may differ between female sex workers (FSWs) and casual partners. We surveyed 203 heterosexual men and investigated the attributes associated with inconsistent condom use among them. Lower educational attainment was positively associated with inconsistent condom use with FSWs (adjusted prevalence ratio (aPR) 2.63; P = 0.018) and casual partners (aPR 1.55; P = 0.022), whereas early age of sexual debut (aPR 3.00; P = 0.012) and alcohol use during sex (aPR 7.95; P < 0.001) were positively associated with inconsistent condom use with FSWs. Socioecological factors may explain such differences.

Liver-Type Glutaminase GLS2 Is a Druggable Metabolic Node in Luminal-Subtype Breast Cancer.

Efforts to target glutamine metabolism for cancer therapy have focused on the glutaminase isozyme GLS. The importance of the other isozyme, GLS2, in cancer has remained unclear, and it has been described as a tumor suppressor in some contexts. Here, we report that GLS2 is upregulated and essential in luminal-subtype breast tumors, which account for >70% of breast cancer incidence. We show that GLS2 expression is elevated by GATA3 in luminal-subtype cells but suppressed by promoter methylation in basal-subtype cells. Although luminal breast cancers resist GLS-selective inhibitors, we find that they can be targeted with a dual-GLS/GLS2 inhibitor. These results establish a critical role for GLS2 in mammary tumorigenesis and advance our understanding of how to target glutamine metabolism in cancer.

How to differentiate uterine leiomyosarcoma from leiomyoma with imaging.

Uterine leiomyomas, the most frequent benign myomatous tumors of the uterus, often cannot be distinguished from malignant uterine leiomyosarcomas using clinical criteria. Furthermore, imaging differentiation between both entities is frequently challenging due to their potential overlapping features. Because a suspected leiomyoma is often managed conservatively or with minimally invasive treatments, the misdiagnosis of leiomyosarcoma for a benign leiomyoma could potentially result in significant treatment delays, therefore increasing morbidity and mortality. In this review, we provide an overview of the differences between leiomyoma and leiomyosarcoma, mainly focusing on imaging characteristics, but also briefly touching upon their demographic, histopathological and clinical differences. The main indications and limitations of available cross-sectional imaging techniques are discussed, including ultrasound, computed tomography, magnetic resonance imaging (MRI) and positron emission tomography/computed tomography. A particular emphasis is placed on the review of specific MRI features that may allow distinction between leiomyomas and leiomyosarcomas according to the most recent evidence in the literature. The potential contribution of texture analysis is also discussed. In order to help guide-imaging diagnosis, we provide an MRI-based diagnostic algorithm which takes into account morphological and functional features, both individually and in combination, in an attempt to optimize radiologic differentiation of leiomyomas from leiomyosarcomas.

Dysregulated Redox Regulation Contributes to Nuclear EGFR Localization and Pathogenicity in Lung Cancer.

Lung cancers are frequently characterized by inappropriate activation of epidermal growth factor receptor (EGFR)-dependent signaling and epigenetic silencing of the NADPH oxidase (NOX) enzyme DUOX1, both potentially contributing to worse prognosis. Based on previous findings linking DUOX1 with redox-dependent EGFR activation, the present studies were designed to evaluate whether DUOX1 silencing in lung cancers may be responsible for altered EGFR regulation. In contrast to normal epithelial cells, EGF stimulation of lung cancer cell lines that lack DUOX1 promotes EGF-induced EGFR internalization and nuclear localization, associated with induction of EGFR-regulated genes and related tumorigenic outcomes. Each of these outcomes could be reversed by overexpression of DUOX1 or enhanced by shRNA-dependent DUOX1 silencing. EGF-induced nuclear EGFR localization in DUOX1-deficient lung cancer cells was associated with altered dynamics of cysteine oxidation of EGFR, and an overall reduction of EGFR cysteines. These various outcomes could also be attenuated by silencing of glutathione S-transferase P1 (GSTP1), a mediator of metabolic alterations and drug resistance in various cancers, and a regulator of cysteine oxidation. Collectively, our findings indicate DUOX1 deficiency in lung cancers promotes dysregulated EGFR signaling and enhanced GSTP1-mediated turnover of EGFR cysteine oxidation, which result in enhanced nuclear EGFR localization and tumorigenic properties.

Pre-discharge prognostic factors of physical function among older adults with hip fracture surgery: a systematic review.

INTRODUCTION: To identify, organize, and assess the evidence level of pre-discharge prognostic factors of physical function beyond discharge after hip fracture surgery. METHODS: We performed a systematic search of four databases (PubMed, Embase, CINAHL, PsycINFO) for longitudinal studies of prognostic factors of physical function at ≥ 1 month among older adults ≥ 50 years old with surgically treated hip fracture, complemented with hand-searching. Two reviewers independently screened papers for inclusion and assessed the quality of all the included papers using the Quality in Prognosis Studies (QUIPS) tool. We assigned the evidence level for each prognostic factor based on consistency in findings and study quality. RESULTS: From 98 papers that met our inclusion criteria, we identified 107 pre-discharge prognostic factors and organized them into the following seven categories: demographic, physical, cognitive, psychosocial, socioeconomic, injury-related, and process of care. Potentially modifiable factors with strong or moderate evidence of an association included total length of stay, physical function at discharge, and grip strength. Factors with strong or moderate evidence of no association included gender, fracture type, and time to surgery. Factors with limited, conflicting, or inconclusive evidence included body-mass index, psychological resilience, depression, and anxiety. CONCLUSIONS: Our findings highlight potentially modifiable prognostic factors that could be targeted and non-modifiable prognostic factors that could be used to identify patients who may benefit from more intensive intervention or to advise patients on their expectations on recovery. Examining the efficacies of existing interventions targeting these prognostic factors would inform future studies and whether any of such interventions could be incorporated into clinical practice.

The effect of dexmedetomidine on delirium and agitation in patients in intensive care: systematic review and meta-analysis with trial sequential analysis.

Delirium is common in intensive care patients. Dexmedetomidine is increasingly used for sedation in this setting, but its effect on delirium remains unclear. The primary aim of this review was to examine whether dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. We sought randomised clinical trials in MEDLINE, EMBASE, PubMed and CENTRAL from their inception until June 2018. Observational studies, case reports, case series and non-systematic reviews were excluded. Twenty-five trials including 3240 patients were eligible for inclusion in the data synthesis. In the patients who received dexmedetomidine (eight trials, 1425 patients), delirium was reduced, odds ratio (95%CI) 0.36 (0.26-0.51), p < 0.001 and high quality of evidence. The use of dexmedetomidine was associated with a reduced incidence of agitation, OR (95%CI) 0.34 (0.20-0.59), p < 0.001, moderate quality of evidence. Patients who were randomly assigned to dexmedetomidine had a significantly higher incidence of bradycardia, OR (95%CI) 2.18 (1.46-3.24), p < 0.001, moderate quality of evidence; and hypotension, OR (95%CI) 1.89 (1.48-2.41), p < 0.001, high quality of evidence. We found no evidence of an effect on mortality, OR (95%CI) 0.86 (0.66-1.10), p = 0.23, moderate quality of evidence. The trial sequential analyses for the incidence of delirium, bradycardia and hypotension was conclusive but not for the incidence of agitation and mortality. In summary, this meta-analysis suggests that dexmedetomidine reduces the incidence of delirium and agitation in intensive care patients. The general quality of evidence ranged from moderate to high.

Anterior Cable Reconstruction Using the Proximal Biceps Tendon for Large Rotator Cuff Defects Limits Superior Migration and Subacromial Contact Without Inhibiting Range of Motion: A Biomechanical Analysis.

PURPOSE: To assess an anterior cable reconstruction (ACR) using autologous proximal biceps tendon for large to massive rotator cuff tears. METHODS: Nine cadaveric shoulders (mean age, 58 years) were tested with a custom testing system. Range of motion, superior translation of the humeral head, and subacromial contact pressure were measured at 0°, 30°, 60°, and 90° of external rotation (ER) with 0°, 20°, and 40° of glenohumeral abduction. Five conditions were tested: intact, stage II tear (supraspinatus), stage II tear + ACR, stage III tear (supraspinatus + anterior half of infraspinatus), and stage III tear + ACR. ACR involved a biceps tendon tenotomy at the transverse humeral ligament, preserving its labral attachment. ACR included nonpenetrating suture-loop fixation using 2 side-to-side sutures and an anchor at the articular margin to restore anatomy and secure the tendon along the anterior edge of the cuff defect. ACR was performed in 20° glenohumeral abduction and 60° ER. RESULTS: ACR for both stage II and stage III showed significantly higher total range of motion compared with intact at all angles (P ≤ .001). ACR significantly decreased superior translation for stage II tears at 0°, 30°, and 60° ER for both 0° and 20° abduction (P ≤ .01) and for stage III tears at 0° and 30° ER for both 0° and 20° abduction (P ≤ .004). ACR for stage III tear significantly reduced peak subacromial contact pressure at 30° and 60° ER with 0° and 40° abduction and at 30° ER with 20° abduction (P ≤ .041). CONCLUSIONS: ACR using autologous biceps tendon biomechanically normalized superior migration and subacromial contact pressure, without limiting range of motion. CLINICAL RELEVANCE: ACR may improve rotator cuff tendon repair longevity by providing basic static ligamentous support to the dynamic tendon while helping to limit superior migration without restricting glenohumeral kinematics.