bluuebunny/crossref_metadata_2025_split huggingface dataset:
The introduction of plastic and reconstructive surgery to the University of Glasgow undergraduate medical core curriculum.
Authors: Higgins Gillian , Thomson Suzanne Emma 
Published: November 2019

AbstractMisperceptions of plastic surgery remain common among medical students and the medical community. This creates barriers in recruitment to specialty and patient referral. Before this study, there was no formal plastic surgery teaching in University of Glasgow undergraduate medical core curriculum. A plastic surgery teaching pilot was implemented for fourth year students. Oncoplastic breast surgery was used as an example of gold standard multidisciplinary reconstructive surgery. Surveys collected data before and after provision of teaching across four parameters; identification of plastic surgery subspecialties, understanding of plastic surgery, opinion of the pilot and curriculum, career preferences and gender. The response rate was 57% (n=160). The most and least recognised subspecialties were burns (48% (n=75)) and perineal and lower limb reconstruction (0% (n=0)), respectively, with more students identifying aesthetic surgery (16% (n=26)) than hand (9% (n=15)) or skin cancer surgery (6% (n=9)). The majority (129 (81%)) thought plastic surgery was poorly represented in their curriculum and wanted further information (98 (61%)). Reported understanding of plastic surgery significantly improved (p≤0.00005). Those interested in surgical careers increased from 39% (n=63) to 41% (n=66) with more males than females reporting interest (p≤0.05). This study introduced plastic and reconstructive surgery into the undergraduate curriculum and led to further increased plastic surgery teaching. It improved student understanding, desire to gain more experience in the specialty and interest in surgical careers. Teaching students about subspecialties is vital to dispel misconceptions, ensure appropriate referrals and ignite interest in those with aptitude for surgical careers.
Delivery of long-term-injectable agents for TB by lay carers: pragmatic randomised trial
Authors: Cohen Danielle B , Mbendera Kuzani , Maheswaran Hendramoorthy , Mukaka Mavuto , Mangochi Helen , Phiri Linna , Madan Jason , Davies Geraint , Corbett Elizabeth , Squire Bertel 
Published: November 2019

BackgroundPeople with recurrent or drug-resistant TB require long courses of intramuscular injections. We evaluate a novel system in which patient-nominated lay carers were trained to deliver intramuscular injections to patients in their own homes.MethodsA pragmatic, individually randomised non-inferiority trial was conducted at two hospitals in Malawi. Adults starting TB retreatment were recruited. Patients randomised to the intervention received home-based care from patient-nominated lay people trained to deliver intramuscular streptomycin. Patients receiving standard care were admitted to hospital for 2 months of streptomycin. The primary outcome was successful treatment (alive and on treatment) at the end of the intervention.ResultsOf 456 patients screened, 204 participants were randomised. The trial was terminated early due to futility. At the end of the intervention, 97/101 (96.0%) in the hospital arm were still alive and on treatment compared with 96/103 (93.2%) in the home-based arm (risk difference −0.03 (95% CI −0.09 to 0.03); p value 0.538). There were no differences in the proportion completing 8 months of anti-TB treatment; or the proportion experiencing 2-month sputum culture conversion. The mean cost of hospital-based management was US$1546.3 per person, compared to US$729.2 for home-based management. Home-based care reduced risk of catastrophic household costs by 84%.ConclusionsAlthough this trial failed to meet target recruitment, the available data demonstrate that training patient-nominated lay people has potential to provide a feasible solution to the operational challenges associated with delivering long-term-injectable drugs to people with recurrent or drug-resistant TB in resource-limited settings, and substantially reduce costs. Further data under operational conditions are required.Trial registration numberISRCTN05815615.
Cardiac ischemia-reperfusion injury induces ROS-dependent loss of PKA regulatory subunit RIα
Authors: Haushalter Kristofer J. , Schilling Jan M. , Song Young , Sastri Mira , Perkins Guy A. , Strack Stefan , Taylor Susan S. , Patel Hemal H. 
Published: November 2019

Type I PKA regulatory α-subunit (RIα; encoded by the Prkar1a gene) serves as the predominant inhibitor protein of the catalytic subunit of cAMP-dependent protein kinase (PKAc). However, recent evidence suggests that PKA signaling can be initiated by cAMP-independent events, especially within the context of cellular oxidative stress such as ischemia-reperfusion (I/R) injury. We determined whether RIα is actively involved in the regulation of PKA activity via reactive oxygen species (ROS)-dependent mechanisms during I/R stress in the heart. Induction of ex vivo global I/R injury in mouse hearts selectively downregulated RIα protein expression, whereas RII subunit expression appears to remain unaltered. Cardiac myocyte cell culture models were used to determine that oxidant stimulus (i.e., H2O2) alone is sufficient to induce RIα protein downregulation. Transient increase of RIα expression (via adenoviral overexpression) negatively affects cell survival and function upon oxidative stress as measured by increased induction of apoptosis and decreased mitochondrial respiration. Furthermore, analysis of mitochondrial subcellular fractions in heart tissue showed that PKA-associated proteins are enriched in subsarcolemmal mitochondria (SSM) fractions and that loss of RIα is most pronounced at SSM upon I/R injury. These data were supported via electron microscopy in A-kinase anchoring protein 1 (AKAP1)-knockout mice, where loss of AKAP1 expression leads to aberrant mitochondrial morphology manifested in SSM but not interfibrillar mitochondria. Thus, we conclude that modification of RIα via ROS-dependent mechanisms induced by I/R injury has the potential to sensitize PKA signaling in the cell without the direct use of the canonical cAMP-dependent activation pathway.NEW & NOTEWORTHY We uncovered a previously undescribed phenomenon involving oxidation-induced activation of PKA signaling in the progression of cardiac ischemia-reperfusion injury. Type I PKA regulatory subunit RIα, but not type II PKA regulatory subunits, is dynamically regulated by oxidative stress to trigger the activation of the catalytic subunit of PKA in cardiac myocytes. This effect may play a critical role in the regulation of subsarcolemmal mitochondria function upon the induction of ischemic injury in the heart.
Caspase lesions of PVN-projecting MnPO neurons block the sustained component of CIH-induced hypertension in adult male rats
Authors: Marciante Alexandria B. , Wang Lei A. , Little Joel T. , Cunningham J. Thomas 
Published: November 2019

Obstructive sleep apnea is characterized by interrupted breathing that leads to cardiovascular sequelae including chronic hypertension that can persist into the waking hours. Chronic intermittent hypoxia (CIH), which models the hypoxemia associated with sleep apnea, is sufficient to cause a sustained increase in blood pressure that involves the central nervous system. The median preoptic nucleus (MnPO) is an integrative forebrain region that contributes to blood pressure regulation and neurogenic hypertension. The MnPO projects to the paraventricular nucleus (PVN), a preautonomic region. We hypothesized that pathway-specific lesions of the projection from the MnPO to the PVN would attenuate the sustained component of chronic intermittent hypoxia-induced hypertension. Adult male Sprague-Dawley rats (250–300 g) were anesthetized with isoflurane and stereotaxically injected bilaterally in the PVN with a retrograde Cre-containing adeno-associated virus (AAV; AAV9.CMV.HI.eGFP-Cre.WPRE.SV40) and injected in the MnPO with caspase-3 (AAV5-flex-taCasp3-TEVp) or control virus (AAV5-hSyn-DIO-mCherry). Three weeks after the injections the rats were exposed to a 7-day intermittent hypoxia protocol. During chronic intermittent hypoxia, controls developed a diurnal hypertension that was blunted in rats with caspase lesions. Brain tissue processed for FosB immunohistochemistry showed decreased staining with caspase-induced lesions of MnPO and downstream autonomic-regulating nuclei. Chronic intermittent hypoxia significantly increased plasma levels of advanced oxidative protein products in controls, but this increase was blocked in caspase-lesioned rats. The results indicate that PVN-projecting MnPO neurons play a significant role in blood pressure regulation in the development of persistent chronic intermittent hypoxia hypertension.NEW & NOTEWORTHY Chronic intermittent hypoxia associated with obstructive sleep apnea increases oxidative stress and leads to chronic hypertension. Sustained hypertension may be mediated by angiotensin II-induced neural plasticity of excitatory median preoptic neurons in the forebrain that project to the paraventricular nucleus of the hypothalamus. Selective caspase lesions of these neurons interrupt the drive for sustained hypertension and cause a reduction in circulating oxidative protein products. This indicates that a functional connection between the forebrain and hypothalamus is necessary to drive diurnal hypertension associated with intermittent hypoxia. These results provide new information about central mechanisms that may contribute to neurogenic hypertension.
Hemodynamic effects of myocardial bridging in patients with hypertrophic cardiomyopathy
Authors: Sharzehee Mohammadali , Chang Yuan , Song Jiang-ping , Han Hai-Chao 
Published: November 2019

Myocardial bridging (MB) is linked to angina and myocardial ischemia and may lead to sudden cardiac death in patients with hypertrophic cardiomyopathy (HCM). However, it remains unclear how MB affect the coronary blood flow in HCM patients. The aim of this study was to assess the effects of MB on coronary hemodynamics in HCM patients. Fifteen patients with MB (7 HCM and 8 non-HCM controls) in their left anterior descending (LAD) coronary artery were chosen. Transient computational fluid dynamics (CFD) simulations were conducted in anatomically realistic models of diseased (with MB) and virtually healthy (without MB) LAD from these patients, reconstructed from biplane angiograms. Our CFD simulation results demonstrated that dynamic compression of MB led to diastolic flow disturbances and could significantly reduce the coronary flow in HCM patients as compared with non-HCM group ( P < 0.01). The pressure drop coefficient was remarkably higher ( P < 0.05) in HCM patients. The flow rate change is strongly correlated with both upstream Reynolds number and MB compression ratio, while the MB length has less impact on coronary flow. The hemodynamic results and clinical outcomes revealed that HCM patients with an MB compression ratio higher than 65% required a surgical intervention. In conclusion, the transient MB compression can significantly alter the diastolic flow pattern and wall shear stress distribution in HCM patients. HCM patients with severe MB may need a surgical intervention. NEW & NOTEWORTHY In this study, the hemodynamic significance of myocardial bridging (MB) in patients with hypertrophic cardiomyopathy (HCM) was investigated to provide valuable information for surgical decision-making. Our results illustrated that the transient MB compression led to complex flow patterns, which can significantly alter the diastolic flow and wall shear stress distribution. The hemodynamic results and clinical outcomes demonstrated that patients with HCM and an MB compression ratio higher than 65% required a surgical intervention.
Twist1-Induced Epithelial Dissemination Requires Prkd1 Signaling
Authors: Georgess Dan , Padmanaban Veena , Sirka Orit Katarina , Coutinho Kester , Choi Alex , Frid Gabriela , Neumann Neil M. , Inoue Takanari , Ewald Andrew J. 
Published: November 2019

Abstract

Dissemination is an essential early step in metastasis but its molecular basis remains incompletely understood. To define the essential targetable effectors of this process, we developed a 3D mammary epithelial culture model, in which dissemination is induced by overexpression of the transcription factor Twist1. Transcriptomic analysis and ChIP-PCR together demonstrated that protein kinase D1 (Prkd1) is a direct transcriptional target of Twist1 and is not expressed in the normal mammary epithelium. Pharmacologic and genetic inhibition of Prkd1 in the Twist1-induced dissemination model demonstrated that Prkd1 was required for cells to initiate extracellular matrix (ECM)–directed protrusions, release from the epithelium, and migrate through the ECM. Antibody-based protein profiling revealed that Prkd1 induced broad phosphorylation changes, including an inactivating phosphorylation of β-catenin and two microtubule depolymerizing phosphorylations of Tau, potentially explaining the release of cell–cell contacts and persistent activation of Prkd1. In patients with breast cancer, TWIST1 and PRKD1 expression correlated with metastatic recurrence, particularly in basal breast cancer. Prkd1 knockdown was sufficient to block dissemination of both murine and human mammary tumor organoids. Finally, Prkd1 knockdown in vivo blocked primary tumor invasion and distant metastasis in a mouse model of basal breast cancer. Collectively, these data identify Prkd1 as a novel and targetable signaling node downstream of Twist1 that is required for epithelial invasion and dissemination.

Significance:
Twist1 is a known regulator of metastatic cell behaviors but not directly targetable. This study provides a molecular explanation for how Twist1-induced dissemination works and demonstrates that it can be targeted.
α-Particle–Emitter Radiopharmaceutical Therapy: Resistance Is Futile
Authors: Sgouros George 
Published: November 2019

Abstract
Alpha-emitter radiopharmaceutical therapy (α-RPT) is a treatment modality that is impervious to conventional cellular resistance mechanisms because of the unique properties of the α-particle. Radiobiological studies of α-particle emitters have been few as they require detailed consideration of both biology and physics. Clinical studies of this radiation delivery modality have shown highly promising results in cancers that are resistant to other treatments. The work by Yard and colleagues published in this issue introduces an innovative approach to radiobiological investigations of α-RPT and highlights the specific physics considerations required to properly investigate this multidisciplinary treatment modality.
See related article by Yard et al., p. 5640
Corpos doentes, curas extraordinárias
Authors: Santos Gabriela Aparecida dos 
Published: November 2019

Resumo
O artigo analisa Notice de géographie médicale: quelques observations sur les maladies des indigènes des provinces de Lourenço Marques et de Gaza, escrito por Georges-Louis Liengme (1859-1936), reconstituindo a confluência entre a medicina como prática social e o paradigma civilizatório que o levou a viajar para o sul do atual território de Moçambique no ano de 1891. Dominando a gramática clínica apoiada no poder de intervenção e de controle diretos sobre o indivíduo, Liengme buscou decodificar o universo africano pelo signo da doença e sob a perspectiva de corpos particularmente enfermos, à espera da ação de governos e sociedades missionárias. Para intervir nesse mundo em desordem, de loucuras e de cegueiras, o seu olhar se voltou para os referentes capazes de produzir “conexões de sentido” e “convergência de horizontes simbólicos” com as populações, mas, nesse processo, avançou em direção a uma liminaridade que acabou por subverter o sentido de sua própria presença.
Observations of Typhoon Waves in a Reef Lagoon of the South China Sea
Authors: Cai Z. W. , Chen W. W. , Liu X. L. , Sun Z. 
Published: November 2019

AbstractBased on wave measurements lasting three and a half years, typhoon wave characteristics in a lagoon of the South China Sea are discussed in this paper. According to the upper boundaries of wind speed and significant wave height Hs, the maximum wave height has a similar rate of change as the maximum wind speed. The peak frequencies decrease in the approaching stage and are concentrated with an average of 0.1415 Hz in the leaving stage. The distributions of the wind and wave directions indicate that the local wind waves and the waves from the open sea propagated to the site in the approaching and leaving stages, respectively. Wind waves generated inside the lagoon are fetch-trapped, and the spectra can be described by αf(−4) or βk(−2.5) when f > fp. In addition, the measurements show that the nondimensional maximum spectrum can be estimated by the nondimensional fetch. The spectra of the waves from the open sea can be described by . Parameters a and c are determined by the nondimensional peak frequency. In addition, it is found that the peak energy density S(fp) is a linear function of for all waves.
Radiologic Evaluation of the Effect of Distal Tibiofibular Joint Anatomy on Arthroscopically Proven Ankle Instability
Authors: Ataoğlu Muhammet Baybars , Tokgöz Mehmet Ali , Köktürk Anıl , Ergişi Yılmaz , Hatipoğlu Mustafa Yasin , Kanatlı Ulunay 
Published: November 2019

Background: Ankle sprains occur frequently in both athletes and the general population. The social and economic consequences can be significant. In an effort to understand the injury, dynamic and static structures around the ankle have been investigated in detail, but anatomical factors predisposing to lateral ankle instability have not been fully clarified. The aim of this study was to radiologically investigate the relationship between bony variations of the distal tibiofibular joint and arthroscopically proven ankle instability. Methods: Fifty patients with arthroscopically proven ankle instability and 50 patients without instability were included in this study. Measurements were obtained from a magnetic resonance imaging (MRI) section 1 cm proximal to the tibiotalar joint; distal tibiofibular joint anterior facet length ( a), posterior facet length ( b), angle between the anterior and posterior facets ( c), fibular notch depth ( d), tibia thickness ( e), and fibula thickness ( f) was measured. Results: It was found that instability was more frequent when the length of a ( P < .001) and e ( P < .001) were shorter. In addition, when value of a/ b and e/f were evaluated, it was observed that the number of individuals who had instability increased as the ratio became smaller ( P < .016-.020, respectively). Pearson correlation analysis indicated strong negative correlation between the values of a- e and instability ( r = −0.348, P < .001, and r = −0.328, P = .001; respectively). Conclusion: Lateral ankle sprains are common, and a clear understanding of the relevant structures and clinical function of the ankle complex should extend beyond the talocrural joint. This study demonstrated that the presence of narrow anterior facet ( a) and thinner tibia ( e) were strongly correlated with lateral ankle instability. Level of Evidence: Level III, retrospective case control study.
PICC-PORT totally implantable vascular access device in breast cancer patients undergoing chemotherapy
Authors: Bertoglio Sergio , Cafiero Ferdinando , Meszaros Paolo , Varaldo Emanuela , Blondeaux Eva , Molinelli Chiara , Minuto Michele 
Published: November 2019

Background and objectives: The increasing use of arm totally implantable vascular access devices for breast cancer patients who require chemotherapy has led to a greater risk of complications and failures and, in particular, to upper extremity deep vein thrombosis. This study aims to investigate the outcomes of the arm peripherally inserted central catheter-PORT technique in breast cancer patients. Methods: The peripherally inserted central catheter-PORT technique is an evolution of the standard arm-totally implantable vascular access device implant based on guided ultrasound venous access in the proximal third of the upper limb with subsequent placement of the reservoir at the middle third of the arm. A prospective study was conducted on 418 adult female breast cancer patients undergoing chemotherapy. The primary study outcome was peripherally inserted central catheter-PORT failure. Results: Median follow-up was 215 days. Complications occurred in 29 patients (6.9%) and failure resulting in removal of the device in 11 patients (2.6%). The main complication we observed was upper extremity deep vein thrombosis, 10 (2.4%); all patients were rescued by anticoagulant treatment without peripherally inserted central catheter-PORT removal. The main reason for removal was reservoir pocket infection: 4 (0.9%) with an infection rate of 0.012 per 1000 catheter days. Cumulative 1-year risk of failure was 3.6% (95% confidence interval, 1.3%–7.1%). With regard to the patients’ characteristics, body mass index <22.5 was the only significant risk for failure ( p = 0.027). Conclusion: The peripherally inserted central catheter-PORT is a safe vascular device for chemotherapy delivery that achieves similar clinical results as traditional long-term vascular access devices (peripherally inserted central catheter and arm totally implantable vascular access device, in particular) in breast cancer patients.
Efficacy of alemtuzumab over 6 years in relapsing–remitting multiple sclerosis patients who relapsed between courses 1 and 2: Post hoc analysis of the CARE-MS studies
Authors: Van Wijmeersch Bart , Singer Barry A , Boster Aaron , Broadley Simon , Fernández Óscar , Freedman Mark S , Izquierdo Guillermo , Lycke Jan , Pozzilli Carlo , Sharrack Basil , Steingo Brian , Wiendl Heinz , Wray Sibyl , Ziemssen Tjalf , Chung Luke , Margolin David H , Thangavelu Karthinathan , Vermersch Patrick 
Published: November 2019

Background: Alemtuzumab is administered as two annual courses for relapsing–remitting multiple sclerosis (MS). Patients may relapse before completing the two-course regimen. Objective: The objective was to evaluate 6-year outcomes in patients who relapsed between alemtuzumab Courses 1 and 2 (early relapsers). Methods: Post hoc analysis of patients from the Comparison of Alemtuzumab and Rebif® Efficacy in Multiple Sclerosis (CARE-MS) studies who enrolled in the extension. Results: Early relapsers (CARE-MS I: 15%; CARE-MS II: 24%) had more relapses in 1–2 years pre-alemtuzumab and higher mean baseline Expanded Disability Status Scale score than patients without relapse. Their annualized relapse rate declined from Year 1 (CARE-MS I: 1.3; CARE-MS II: 1.2) to Year 2 following Course 2 (0.3; 0.5) and remained low thereafter. Over 6 years, 60% remained free of 6-month confirmed disability worsening; 24% (CARE-MS I) and 34% (CARE-MS II) achieved 6-month confirmed disability improvement. During Year 6, 69% (CARE-MS I) and 68% (CARE-MS II) were free of magnetic resonance imaging (MRI) disease activity. Median percent yearly brain volume loss (Year 1: −0.67% (CARE-MS I); −0.47% (CARE-MS II)) declined after Course 2 (Year 6: −0.24%; −0.13%). Conclusion: Early relapsers’ outcomes improved after completing the second alemtuzumab course. These findings support administering the approved two-course regimen to maximize clinical benefit. ClinicalTrials.gov registration numbers: CARE-MS I, II, extension: NCT00530348, NCT00548405, NCT00930553.