Van Gogh-like 2 is essential for the architectural patterning of the mammalian biliary tree.

BACKGROUND & AIMS: In the developing liver, bipotent epithelial progenitor cells undergo lineage segregation to form hepatocytes, which constitute the bulk of the liver parenchyma, and biliary epithelial cells (cholangiocytes), which comprise the bile duct (a complex tubular network that is critical for normal liver function). Notch and TGFß signalling promote the formation of a sheet of biliary epithelial cells, the ductal plate, that organises into discontinuous tubular structures. How these structures elongate and connect to form a continuous duct remains undefined. We aimed to define the mechanisms by which the ductal plate transitions from a simple sheet of epithelial cells into a complex and connected bile duct. METHODS: By combining single-cell RNA sequencing of embryonic mouse livers with genetic tools and organoid models we functionally dissected the role of planar cell polarity in duct patterning. RESULTS: We show that the planar cell polarity protein VANGL2 is expressed late in intrahepatic bile duct development and patterns the formation of cell-cell contacts between biliary cells. The patterning of these cell contacts regulates the normal polarisation of the actin cytoskeleton within biliary cells and loss of Vangl2 function results in the abnormal distribution of cortical actin remodelling, leading to the failure of bile duct formation. CONCLUSIONS: Planar cell polarity is a critical step in the post-specification sculpture of the bile duct and is essential for establishing normal tissue architecture. IMPACT AND IMPLICATIONS: Like other branched tissues, such as the lung and kidney, the bile ducts use planar cell polarity signalling to coordinate cell movements; however, how these biochemical signals are linked to ductular patterning remains unclear. Here we show that the core planar cell polarity protein VANGL2 patterns how cell-cell contacts form in the mammalian bile duct and how ductular cells transmit confluent mechanical changes along the length of a duct. This work sheds light on how biological tubes are patterned across mammalian tissues (including within the liver) and will be important in how we promote ductular growth in patients where the duct is mis-patterned or poorly formed.

The reliability of posterior malleolar ankle fracture assessment: a unique perspective.

AIM: This study aims to elucidate the pathology of PMFs in the South African population, establish correlations between fracture patterns and international classification guidelines and evaluate the interobserver reliability of current classifications. METHODS: A retrospective review was conducted in a multicentre analysis over a one-year period from January 2019 to December 2019 at our institution. Computer tomography scans for foot and ankle injuries were reviewed, and posterior malleolus fractures were included. Pathoanatomical data was collected and analysed according to known classification systems and subsequent treatment modalities evaluated. A panel of observers individually reviewed radiographic data to determine interobserver reliability. RESULTS: A total of 71 patients were included with a mean age of 41 ± 13.4 years (range 18-78) and a female predominant population (69%). A greater proportion of injuries were high energy (23.9%), with significant fragment comminution (53.5%), and half (52.1%) of all injuries were subluxated/dislocated at presentation. A total of 93% of injuries were managed operatively, despite theatre access limitations resulting in significant delays to fixation (19.1 days). Despite good pathoanatomical agreement with most international classifications, interobserver reliability was poor (Krippendorff α-coefficient < 0.667). Inconsistent treatment patterns in operative and non-operative strategies are reported. CONCLUSION: A unique patient population of younger, female individuals incurred posterior malleolar fractures due to higher energy mechanisms of injury. Whilst injury patterns were mostly comparable, significant interobserver variability was noted. Resource limitations, diagnostic challenges, poorly defined and inconsistent treatment strategies, inevitably impact outcomes within the South African population. LEVEL OF EVIDENCE: Level III.

Correction: Predictors of Health Information-Seeking Behavior: Systematic Literature Review and Network Analysis.

[This corrects the article DOI: 10.2196/21680.].

Predictors of Health Information-Seeking Behavior: Systematic Literature Review and Network Analysis.

BACKGROUND: People engage in health information-seeking behavior to support health outcomes, and being able to predict such behavior can inform the development of interventions to guide effective health information seeking. Obtaining a comprehensive list of the predictors of health information-seeking behavior through a systematic search of the literature and exploring the interrelationship of these predictors are critical first steps in this process. OBJECTIVE: This study aims to identify significant predictors of health information-seeking behavior in the primary literature, develop a common taxonomy for these predictors, and identify the evolution of the concerned research field. METHODS: A systematic search of PsycINFO, Scopus, and PubMed was conducted for all years up to and including December 10, 2019. Quantitative studies identifying significant predictors of health information-seeking behavior were included. Information seeking was broadly defined and not restricted to any source of health information. Data extraction of significant predictors was performed by 2 authors, and network analysis was conducted to observe the relationships between predictors with time. RESULTS: A total of 9549 articles were retrieved, and after the screening, 344 studies were retained for analysis. A total of 1595 significant predictors were identified. These predictors were categorized into 67 predictor categories, with the most central predictors being age, education, gender, health condition, and financial income. With time, the interrelationship of predictors in the network became denser, with the growth of new predictor grouping reaching saturation (1 new predictor identified) in the past 7 years, despite increasing publication rates. CONCLUSIONS: A common taxonomy was developed to classify 67 significant predictors of health information-seeking behavior. A time-aggregated network method was developed to track the evolution of the research field, showing the maturation of new predictor terms and an increase in primary studies reporting multiple significant predictors of health information-seeking behavior. The literature has evolved with a decreased characterization of novel predictors of health information-seeking behavior. In contrast, we identified a parallel increase in the complexity of predicting health information-seeking behavior, with an increase in the literature describing multiple significant predictors.

Estimating the Effect of the New York State Nurse Practitioners Modernization Act on Care Received by Medicaid Patients.

The demand for primary care services may surpass the supply of primary care providers, exacerbating challenges with access, quality, and cost in the U.S. health care system. Expanding the supply of, and access to, nurse practitioner (NP) care has been proposed as one method to alleviate these challenges. New York State (NYS) changed its regulatory environment for NPs in 2015. We estimate the impact of expanded NP scope of practice (SOP) regulations in NYS on total care days received by Medicaid beneficiaries from 2015 to 2018 using a model derived from national historical data from 1999 to 2011. We used a longitudinal data policy analysis framework and a generalized difference-in-differences model to identify the effect of changes in NP SOP regulations on total care days. The model included controls for state income and unemployment rates. Our results suggest that the policy change increased total care days provided to patients, but that this difference was not statistically significant and became negligible after computing the number of days per beneficiary. In addition, our results suggest that had NYS moved to a full practice environment, more care days could have been provided to Medicaid patients, and this difference was found to be statistically significant. Our results suggest that states should adopt full NP SOP practice environments to realize measurable benefits of expanded NP SOP.

"A Bend to a Needle Makes the Arch Stable" a Modified Technique for Zygomatic Arch Reduction and Stabilization.

BACKGROUND: Gillies temporal approach and intra oral supraperiosteal approach are the most commonly used approaches for reduction of isolated zygomatic arch fractures. PURPOSE: To set forth a less invasive technique for reduction and stabilization of isolated zygomatic arch fractures. MATERIALS AND METHODS: A 24-G stainless steel wire is passed through a 16-G cannula needle and is shaped to form a semi-circle. The precontoured needle was then inserted into the inferior part of the depressed zygomatic arch and the tip passed out through the superior part. The wires are then twisted and pulled laterally to reduce the fracture and are tied over an external splint to stabilize the arch. CONCLUSION: The technique discussed in this article is simple, less time consuming, cost effective and less traumatic than the conventionally performed techniques for reduction and stabilization of isolated zygomatic arch fractures.

Minimising risk to thoracic surgical teams in an era of COVID-19: exploring possible preventative measures.

The demands of curtailing the impact of the coronavirus disease 2019 (COVID-19) global pandemic have disrupted the world's ability to care for patients with thoracic pathologies. Those who undergo thoracic surgical therapeutic procedures are a high-risk category, likely to have impaired lung function but also high risk for exposing clinical teams to aerosolised viral loads. In light of this global pandemic, thorough pre-procedural planning, adequate personal protective equipment (PPE), experienced personnel and judicious anaesthetic and intra-operative measures will serve to be instrumental in ensuring positive patient outcomes whilst still protecting the safety of healthcare workers.

Association between early essential newborn care and breastfeeding outcomes in eight countries in Asia and the Pacific: a cross-sectional observational -study.

OBJECTIVE: To explore the association between early essential newborn care (EENC) policy, practice and environmental interventions and breastfeeding outcomes. DESIGN: Cross-sectional observational study. SETTING: 150 national, provincial and district hospitals implementing EENC in eight countries in East Asia and the Pacific. PARTICIPANTS: 1383 maternal interviews, chart reviews and environmental assessments during 2016 and 2017. MAIN OUTCOME MEASURES: Exclusive breastfeeding (EBF), that is, feeding only breastmilk without other food or fluids since birth and before discharge, and, early breastfeeding initiation, that is, during skin-to-skin contact (SSC) with the mother without separation. RESULTS: Fifty-nine per cent of newborns initiated breastfeeding early and 83.5% were EBF. Duration of SSC showed a strong dose-response relationship with early breastfeeding initiation. SSC of at least 90 min was associated with 368.81 (95% CI 88.76 to 1532.38, p<0.001) times higher early breastfeeding. EBF was significantly associated with SSC duration of 30-59 min (OR 3.54, 95% CI 1.88 to 6.66, p<0.001), 60-89 min (OR 5.61, 95% CI 2.51 to 12.58, p<0.001) and at least 90 min (OR 3.78, 95% CI 2.12 to 6.74, p<0.001) regardless of delivery mode. Non-supine position (OR 2.80, 95% CI 1.90 to 4.11, p<0.001), rooming-in (OR 5.85, 95% CI 3.46 to 9.88, p<0.001), hospital breastfeeding policies (OR 2.82, 95% CI 1.97 to 4.02, p<0.001), quality improvement mechanisms (OR 1.63, 95% CI 1.07 to 2.49, p=0.02) and no formula products (OR 17.50, 95% CI 5.92 to 51.74, p<0.001) were associated with EBF. CONCLUSION: EENC policy, practice and environmental interventions were associated with breastfeeding outcomes. To maximise the likelihood of early and EBF, newborns, regardless of delivery mode, should receive immediate and uninterrupted SSC for at least 90 min.

Erratum to: Comparing the Efficiency of Two Different Extraction Techniques in Removal of Maxillary Third Molars: A Randomized Controlled Trial.

[This corrects the article DOI: 10.1007/s12663-016-0935-1.].

Comparing the Efficiency of Two Different Extraction Techniques in Removal of Maxillary Third Molars: A Randomized Controlled Trial.

INTRODUCTION: Extractions are routine procedures in dental surgery. Traditional extraction techniques use a combination of severing the periodontal attachment, luxation with an elevator, and removal with forceps. A new technique of extraction of maxillary third molar is introduced in this study-Joedds technique, which is compared with the conventional technique. METHODS AND MATERIAL: One hundred people were included in the study, the people were divided into two groups by means of simple random sampling. In one group conventional technique of maxillary third molar extraction was used and on second Joedds technique was used. Statistical analysis was carried out with student's t test. RESULTS: Analysis of 100 patients based on parameters showed that the novel joedds technique had minimal trauma to surrounding tissues, less tuberosity and root fractures and the time taken for extraction was <2 min while compared to other group of patients. CONCLUSION: This novel technique has proved to be better than conventional third molar extraction technique, with minimal complications. If Proper selection of cases and right technique are used.

The effects of expanded nurse practitioner and physician assistant scope of practice on the cost of Medicaid patient care.

The provision of health care to low-income Americans remains an ongoing policy challenge. In this paper, I examine how important changes to occupational licensing laws for nurse practitioners and physician assistants have affected cost and intensity of health care for Medicaid patients. The results suggest that allowing physician assistants to prescribe controlled substances is associated with a substantial (more than 11%) reduction in the dollar amount of outpatient claims per Medicaid recipient. I find little evidence that expanded scope of practice has affected proxies for care intensity such as total claims and total care days. Relaxing occupational licensing requirements by broadening the scope of practice for healthcare providers may represent a low-cost alternative to providing quality care to America's poor.

Arts, Science, Engineering and Medicine Collaborate to Educate Public on Bioenergetics.

Mitochondrial dysfunction has correlated with a rise in energy deficiency disorders (EDD). The EDDs include mitochondrial disorders, obesity, metabolic disorders, cardiovascular and neurodegenerative disorders. Many individuals in our communities are at high risk of developing these disorders, yet are unaware of it. Our goal was to increase public awareness of mitochondrial health, whilst providing students with an innovative educational experience. We designed a 'Bioenergetics exhibition' by introducing Arts into traditional STEM (Science, Technology, Engineering & Mathematics) disciplines to create a new STEAM-(Health) initiative. Results indicated ~120,000 guests visited the exhibition, including many school-aged children, teachers and families. Comparative analysis of random first-time vs. repeat visitor surveys demonstrated a statistically significant (8.25% at p-value = 0.006) increase in knowledge of mitochondrial disease and bioenergetics. Our findings clearly support the power of the STEAM-H initiative in creatively communicating the complex science to a broader community.

STING-Dependent 2'-5' Oligoadenylate Synthetase-Like Production Is Required for Intracellular Mycobacterium leprae Survival.

Cytosolic detection of nucleic acids elicits a type I interferon (IFN) response and plays a critical role in host defense against intracellular pathogens. Herein, a global gene expression profile of Mycobacterium leprae-infected primary human Schwann cells identified the genes differentially expressed in the type I IFN pathway. Among them, the gene encoding 2'-5' oligoadenylate synthetase-like (OASL) underwent the greatest upregulation and was also shown to be upregulated in M. leprae-infected human macrophage cell lineages, primary monocytes, and skin lesion specimens from patients with a disseminated form of leprosy. OASL knock down was associated with decreased viability of M. leprae that was concomitant with upregulation of either antimicrobial peptide expression or autophagy levels. Downregulation of MCP-1/CCL2 release was also observed during OASL knock down. M. leprae-mediated OASL expression was dependent on cytosolic DNA sensing mediated by stimulator of IFN genes signaling. The addition of M. leprae DNA enhanced nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin intracellular survival, downregulated antimicrobial peptide expression, and increased MCP-1/CCL2 secretion. Thus, our data uncover a promycobacterial role for OASL during M. leprae infection that directs the host immune response toward a niche that permits survival of the pathogen.

STING-Dependent 2'-5' oligoadenylate synthetase-like production is required for intracellular Mycobacterium leprae survival

Cytosolic detection of nucleic acids elicits a type I interferon (IFN) response and plays a critical role in host defense against intracellular pathogens. Herein, a global gene expression profile of Mycobacterium leprae-infected primary human Schwann cells identified the genes differentially expressed in the type I IFN pathway. Among them, the gene encoding 2'-5' oligoadenylate synthetase-like (OASL) underwent the greatest upregulation and was also shown to be upregulated in M. leprae-infected human macrophage cell lineages, primary monocytes, and skin lesion specimens from patients with a disseminated form of leprosy. OASL knock down was associated with decreased viability of M. leprae that was concomitant with upregulation of either antimicrobial peptide expression or autophagy levels. Downregulation of MCP-1/CCL2 release was also observed during OASL knock down. M. leprae-mediated OASL expression was dependent on cytosolic DNA sensing mediated by stimulator of IFN genes signaling. The addition of M. leprae DNA enhanced nonpathogenic Mycobacterium bovis bacillus Calmette-Guerin intracellular survival, downregulated antimicrobial peptide expression, and increased MCP-1/CCL2 secretion. Thus, our data uncover a promycobacterial role for OASL during M. leprae infection that directs the host immune response toward a niche that permits survival of the pathogen.

Video-assisted thoracoscopic lobectomy: operative technique.

In this study, we present our technique for performing video-assisted lobectomy. This is presented in clear, easy-to-follow, sequential steps, noting variations on the most established technique and the rationale for this divergence. We also provide an instrument preference card, some operative tips and high-quality videos.