bluuebunny/crossref_metadata_2025 huggingface dataset:
Prediction of cardiovascular events in rheumatoid arthritis using risk age calculations: evaluation of concordance across risk age models
Authors: Wibetoe Grunde , Sexton Joseph , Ikdahl Eirik , Rollefstad Silvia , Kitas George D. , van Riel Piet , Gabriel Sherine , Kvien Tore K. , Douglas Karen , Sandoo Aamer , Arts Elke E. , Wållberg-Jonsson Solveig , Dahlqvist Solbritt Rantapää , Karpouzas George , Dessein Patrick H. , Tsang Linda , El-Gabalawy Hani , Hitchon Carol A. , Pascual-Ramos Virginia , Contreas-Yañes Irazu , Sfikakis Petros P. , González-Gay Miguel A. , Colunga-Pedraz Iris J. , Galarza-Delgado Dionicio A. , Azpiri-Lopez Jose Ramon , Crowson Cynthia S. , Semb Anne Grete
Published: April 2020

Background

In younger individuals, low absolute risk of cardiovascular disease (CVD) may conceal an increased risk age and relative risk of CVD. Calculation of risk age is proposed as an adjuvant to absolute CVD risk estimation in European guidelines. We aimed to compare the discriminative ability of available risk age models in prediction of CVD in rheumatoid arthritis (RA). Secondly, we also evaluated the performance of risk age models in subgroups based on RA disease characteristics.

Methods

RA patients aged 30–70 years were included from an international consortium named A Trans-Atlantic Cardiovascular Consortium for Rheumatoid Arthritis (ATACC-RA). Prior CVD and diabetes mellitus were exclusion criteria. The discriminatory ability of specific risk age models was evaluated using c-statistics and their standard errors after calculating time until fatal or non-fatal CVD or last follow-up.

Results

A total of 1974 patients were included in the main analyses, and 144 events were observed during follow-up, the median follow-up being 5.0 years. The risk age models gave highly correlated results, demonstrating R2 values ranging from 0.87 to 0.97. However, risk age estimations differed > 5 years in 15–32% of patients. C-statistics ranged 0.68–0.72 with standard errors of approximately 0.03. Despite certain RA characteristics being associated with low c-indices, standard errors were high. Restricting analysis to European RA patients yielded similar results.

Conclusions

The cardiovascular risk age and vascular age models have comparable performance in predicting CVD in RA patients. The influence of RA disease characteristics on the predictive ability of these prediction models remains inconclusive.
Solving time fractional Burgers’ and Fisher’s equations using cubic B-spline approximation method
Authors: Majeed Abdul , Kamran Mohsin , Iqbal Muhammad Kashif , Baleanu Dumitru
Published: April 2020

This article presents a numerical algorithm for solving time fractional Burgers’ and Fisher’s equations using cubic B-spline finite element method. TheL1 formula with Caputo derivative is used to discretized the time fractional derivative, whereas the Crank–Nicolson scheme based on cubic B-spline functions is used to interpolate the solution curve along the spatial grid. The numerical scheme has been implemented on three test problems. The obtained results indicate that the proposed method is a good option for solving nonlinear fractional Burgers’ and Fisher’s equations. The error norms$L_{2}$L2and$L_{\infty }$L∞have been calculated to validate the efficiency and accuracy of the presented algorithm.
Ethiopia’s FDI inflow from India and China: analysis of trends and determinants
Authors: Ergano Degele , Rambabu K.
Published: April 2020

This study analyzes the trends and determinants of FDI inflow to Ethiopia from India and China. It is based on panel data of 2 decades (1997–2016). It employs a gravity model approach and fixed effects estimation technique to identify factors governing the flow of FDI to Ethiopia. Factors affecting the flow of Indian FDI to Ethiopia include Ethiopia’s trade with India, India’s population size, GDP of Ethiopia, GDP PC of India, real interest rate, credit access and FDI openness in Ethiopia. Similarly, factors governing Chinese FDI flow to Ethiopia include Ethiopia’s GDP growth, Ethiopia’s trade with China, FDI openness and secondary school enrolment. Government expenditure in the host country reduces China’s and India’s FDI inflow. The traditional explanatory variable, a resource rent, is not found significant in explaining FDI in flow from China and India. The FDI inflow from India and China showed an increasing trend with an average rate of 82% and 202%, respectively, during the two-decade period. But the overall trend for both partner countries showed fluctuation across years. We can conclude that FDI from India is responsive to macroeconomic variables such as OER, real interest rate and liberalization measures such as trade openness in Ethiopia. FDI and trade flows from China are positively related to one another and cheap labour is an important attraction factor for Chinese FDI inflow. Policy makers in Ethiopia can focus on macroeconomic reform in case of the country’s relation with India whereas they focus on maintaining cheap labour cost, GDP growth and trade transactions with China.
Changes of the glutathione redox system during the weaning transition in piglets, in relation to small intestinal morphology and barrier function
Authors: Degroote Jeroen , Vergauwen Hans , Wang Wei , Van Ginneken Chris , De Smet Stefaan , Michiels Joris
Published: April 2020

Background

Weaning is known to result in barrier dysfunction and villus atrophy in the immediate post-weaning phase, and the magnitude of these responses is hypothesized to correlate with changes in the glutathione (GSH) redox system. Therefore, these parameters were simultaneously measured throughout the weaning phase, in piglets differing in birth weight category and weaning age, as these pre-weaning factors are important determinants for the weaning transition. Low birth weight (LBW) and normal birth weight (NBW) littermates were assigned to one of three weaning treatments; i.e. weaning at 3 weeks of age (3w), weaning at 4 weeks of age (4w) and removal from the sow at 3 d of age and fed a milk replacer until weaning at 3 weeks of age (3d3w). For each of these treatments, six LBW and six NBW piglets were euthanized at 0, 2, 5, 12 or 28 d post-weaning piglets, adding up 180 piglets.

Results

Weaning increased the glutathione peroxidase activity on d 5 post-weaning in plasma, and duodenal and jejunal mucosa. Small intestinal glutathione-S-transferase activity gradually increased until d 12 post-weaning, and this was combined with a progressive rise of mucosal GSH up till d 12 post-weaning. Oxidation of the GSH redox status (GSH/GSSG Eh) was only observed in the small intestinal mucosa of 3d3w weaned piglets at d 5 post-weaning. These piglets also demonstrated increased fluorescein isothiocyanate dextran (FD4) and horseradish peroxidase fluxes in the duodenum and distal jejunum during the experiment, and specifically demonstrated increased FD4 fluxes at d 2 to d 5 post-weaning. On the other hand, profound villus atrophy was observed during the weaning transition for all weaning treatments. Finally, LBW and NBW piglets did not demonstrate notable differences in GSH redox status, small intestinal barrier function and histo-morphology throughout the experiment.

Conclusion

Although moderate changes in the GSH redox system were observed upon weaning, the GSH redox status remained at a steady state level in 3w and 4w weaned piglets and was therefore not associated with weaning induced villus atrophy. Conversely, 3d3w weaned piglets demonstrated GSH redox imbalance in the small intestinal mucosa, and this co-occurred with a temporal malfunction of their intestinal barrier function.
Knowledge and confidence in managing obstructive sleep apnea patients in Canadian otolaryngology - head and neck surgery residents: A cross sectional survey
Authors: Ansari Saad , Hu Amanda
Published: April 2020

Background

Obstructive sleep apnea is an expected competency for Otolaryngology - Head and Neck surgery residents and tested on the Royal College of Physicians and Surgeons examination. Our objective was to evaluate the knowledge, attitudes and confidence of Canadian Otolaryngology - Head and Neck surgery residents in managing Obstructive Sleep Apnea (OSA) patients.

Methods

An anonymous, online, cross-sectional survey was distributed to all current Canadian Otolaryngology-Head and Neck surgery residents according to the Dillman Tailored Design Method in English and French. The previously validated OSA Knowledge and Attitudes (OSAKA) questionnaire was administered, along with questions exploring resident confidence levels with performing OSA surgeries. Descriptive statistics, Wilcoxon Rank Sum and unpaired Student's t tests were calculated in Excel.

Results

Sixty-six (38.4%) out of 172 residents responded (60.6% male; 80.3% English-speaking). Median OSAKA knowledge score was 16/18 (88.9%; Interquartile range: 14–16). Although all respondents believed that OSA was an important clinical disorder, only 45.5% of residents felt confident in managing OSA patients, while only 15.2% were confident in managing continuous positive airway pressure therapy (CPAP). Senior residents were more confident than junior residents in identifying OSA patients (96.7% vs 69.4%; p < 0.005) and managing the disease (60.0% vs. 33.3%; p = 0.03), including CPAP (26.7% vs. 5.6%; p = 0.01). Residents had lowest confidence levels in performing tongue base suspension (1.5%), transpalatal advancement pharyngoplasty (3.0%), and laser assisted uvulopalatoplasty (6.1%). Highest confidence levels were described in performing septoplasty (56.1%), adult tonsillectomy (75.8%), and tracheotomy (77.3%).

Conclusions

Otolaryngology - Head and Neck surgery residents’ knowledge of OSA was very good; however, confidence levels for managing OSA and performing OSA surgeries were varied. Several areas of perceived strengths and weaknesses in OSA training were identified by Canadian Otolaryngology - Head and Neck surgery residents.
Predictive analytics using big data for increased customer loyalty: Syriatel Telecom Company case study
Authors: Wassouf Wissam Nazeer , Alkhatib Ramez , Salloum Kamal , Balloul Shadi
Published: April 2020

Given the growing importance of customer behavior in the business market nowadays, telecom operators focus not only on customer profitability to increase market share but also on highly loyal customers as well as customers who are churn. The emergence of big data concepts introduced a new wave of Customer Relationship Management (CRM) strategies. Big data analysis helps to describe customer’s behavior, understand their habits, develop appropriate marketing plans for organizations to identify sales transactions and build a long-term loyalty relationship. This paper provides a methodology for telecom companies to target different-value customers by appropriate offers and services. This methodology was implemented and tested using a dataset that contains about 127 million records for training and testing supplied by Syriatel corporation. Firstly, customers were segmented based on the new approach (Time-frequency- monetary) TFM (TFM where: Time (T): total of calls duration and Internet sessions in a certain period of time. Frequency (F): use services frequently within a certain period. Monetary (M): The money spent during a certain period.) and the level of loyalty was defined for each segment or group. Secondly, The loyalty level descriptors were taken as categories, choosing the best behavioral features for customers, their demographic information such as age, gender, and the services they share. Thirdly, Several classification algorithms were applied based on the descriptors and the chosen features to build different predictive models that were used to classify new users by loyalty. Finally, those models were evaluated based on several criteria and derive the rules of loyalty prediction. After that by analyzing these rules, the loyalty reasons at each level were discovered to target them the most appropriate offers and services.
Machine learning-selected variables associated with CD4 T cell recovery under antiretroviral therapy in very advanced HIV infection
Authors: Romero-Rodríguez Dámaris P. , Ramírez Carlos , Imaz-Rosshandler Iván , Ormsby Christopher E. , Peralta-Prado Amy , Olvera-García Gustavo , Cervantes Fernanda , Würsch-Molina Daniela , Romero-Rodríguez Jessica , Jiang Wei , Reyes-Terán Gustavo , Espinosa Enrique
Published: April 2020

Background

A considerable portion of the HIV pandemic is composed of people under antiretroviral therapy, many of whom get a late diagnosis. Patients starting antiretroviral therapy (ART) at a very advanced stage of HIV disease attain a low recovery of CD4 T cells. Factors associated with poor recovery are incompletely described. This study aimed at finding variables associated with CD4 T cell recovery in late-presenting HIV patients.

Methods

We studied a cohort of HIV+patients initiating ART with very low basal CD4 T cell counts. We defined immune recovery as the net increase in circulating CD4 T cell counts after one year on ART. We analyzed diverse routine laboratory determinations at different times using Least Absolute Shrinkage and Selection Operator (LASSO), adaptive LASSO and Conditional Inference Random Forest.

Results

CD4/CD8 ratio, % CD4 T cells and CD8 T cell counts at different times were the main recovery correlates, validated by all approaches. Unexpectedly, basal hematocrit was a consistent predictor. Additionally, week 24 creatinine had a high lasso coefficient, and alkaline phosphatase had a high conditional inference random forest coefficients, although neither was verified by other tests.

Conclusions

CD4 T cell proportions are associated with CD4 T cell recovery, independently of cell counts. Inflammation-related variables could also affect reconstitution. These accessible variables may reflect underlying mechanisms and could improve the follow up of patients starting ART with an advanced HIV infection.
What are the optimal measures to identify anxiety and depression in people diagnosed with head and neck cancer (HNC): a systematic review
Authors: Shunmugasundaram Chindhu , Rutherford Claudia , Butow Phyllis N. , Sundaresan Puma , Dhillon Haryana M.
Published: April 2020

Background

A cancer diagnosis is potentially life-threatening, likely causing distress and uncertainty, which may be psychologically debilitating. Depression and anxiety are commonly underdiagnosed and undertreated in cancer patients. Head and neck cancer (HNC) patients face particular challenges that may contribute to distress. This review aims to: i) identify patient reported outcome measures (PROMs) designed to assess anxiety and depression in HNC; and ii) determine their suitability for use in research and clinical practice to screen patients.

Methods

We searched five electronic databases between July 2007 to July 2019 for studies assessing anxiety and depression in HNC patients. Searches were limited to this period to account for advances in cancer treatment. Records were screened for eligibility by one reviewer and 10% cross-checked by a second across all stages of the review. In addition to the electronic searches, PROM databases were searched for additional measures of anxiety and depression. All retrieved PROMs were mapped against Diagnostic and Statistical Manual-5 criteria for anxiety and depression to assess content coverage. Then, their psychometric properties appraised against the COSMIN checklist.

Results

Electronic searches identified 98 records, from which five anxiety and eight depression measures were retrieved. PROM database searches retrieved an additional four anxiety and four depression measures; a total of nine anxiety and 12 depression measures were appraised. Content coverage of anxiety measures ranged from 50% to 75% and depression measures from 42% to 100%. Demonstration of psychometric properties against COSMIN criteria ranged from 57% to 71% for anxiety measures (three PROMs > 70%) and from 29% to 86% for depression measures (nine PROMs > 70%). Three anxiety and seven depression measures had established clinical cut-offs in cancer populations.

Conclusions

The Patient Health Questionnaire-9, Zung Self-rating Depression and Zung Self-rating Anxiety Scales demonstrated good content coverage along with excellent psychometric properties, and thus were considered the most suitable PROMs to assess psychological distress in HNC populations. It is important to have PROMs assessing psychological distress that capture a comprehensive set of subjective symptoms. The identified PROMs will help researchers and health professionals in clinical-decision making, thereby potentially improving quality of life in HNC patients.
Detection of central veins using susceptibility weighted imaging (SWI) for discrimination between lesions in multiple sclerosis (MS) and cerebral small vessel disease (CSVD)
Authors: Anan Rania Adel , El-Adalany Mohamed Ali , Belal Tamer Mohamed Ibrahim , Elmogy Sabry Alam El-Dein
Published: April 2020

Background

Conventional brain MRI cannot always distinguish between different white matter lesions. Susceptibility weighted imaging (SWI) can detect a sign called central vein sign which is suggested to discriminate between multiple sclerosis and other white matter lesions thus increasing the accuracy of MRI in MS diagnosis. This study aimed to evaluate the role of MR susceptibility weighted imaging in differentiating MS from CSVD lesions.

Results

The central vein sign (CVS) was found to have a premium diagnostic performance in diagnosis of MS with sensitivity 83.3%, specificity 70%, positive predictive value 80.6%, and negative predictive value 73.7%. When CVS positive lesions load was ≥ 44.24%, the specificity of CVS in diagnosing MS raised to 100%.

Conclusion

Detection of the CVS on SWI can reliably discriminate between MS and CSVD.
Prevalence of incidentally discovered findings on brain MRI in adult Egyptian population
Authors: Serag Dena , Ragab Eman
Published: April 2020

Background

Apparently, asymptomatic intracranial anomalies of potential clinical significance are becoming problematic, especially with the increase of use of brain MRI by clinicians and researchers. Performing MRI at higher resolution and stronger magnetic field and with more selective sequences has led to the detection of subtle brain anomalies that were not detected previously. Incidental findings are defined as previously undetected anomalies of potential clinical relevance that are unexpectedly detected and not related to the indication of the scan.

Knowing about their existence would help clinicians to inform their patients of the potential risks and plan for long-term follow-up when indicated.

Results

Seven hundred fifty-three neurologically healthy subjects (389 males and 364 females) who underwent MRI scanning of the brain were screened for the presence of incidental findings, and the prevalence of each finding was recorded. Incidental findings were recorded in 11.7% of the subjects with meningiomas being the most commonly encountered finding (2.5%) followed by vascular malformations (aneurysms, cavernomas) in about 2% of the subjects. Meningiomas, cavernomas, and aneurysms had significantly higher prevalence in females than in males. The prevalence of neoplastic incidental findings increased with age, while the detection of non-neoplastic findings seemed to decrease with age.

Conclusion

Incidental findings were relatively common in the adult Egyptian population. The most common findings were meningiomas, followed by vascular malformations and arachnoids cysts. Knowing about their existence will help directing patients towards the proper specialist and plan for appropriate follow-up to avoid potential clinical hazards. It also raises the awareness of the importance of screening the brain scans while scanning the patient for other purposes like scanning the paranasal sinuses, orbits, and petrous temporal bones.
PTSD diagnoses and treatments: closing the gap between ICD-11 and DSM-5
Authors: Lehrner Amy , Yehuda Rachel
Published: April 2020

The diagnostic status of ‘complex’ post-traumatic stress disorder (PTSD) remains controversial. The revisions to PTSD diagnostic criteria in ICD-11 and DSM-5 take opposing positions on how best to conceptualise post-traumatic presentations that include affect dysregulation, interpersonal difficulties and negative self-concept. ICD-11 carved out a separate category of complex PTSD (CPTSD) that is distinct from PTSD, whereas DSM-5 expanded PTSD to encompass such symptoms. Each approach carries problematic implications for clinical care. ICD-11 creates a dichotomy but the criteria themselves suggest a difference in severity rather than category. Furthermore, separating CPTSD perpetuates expectations that a ‘simple’ PTSD can be easily treated with brief trauma-focused therapy. DSM-5 complicates the PTSD diagnosis, but does not revise treatment recommendations. Both ICD and DSM need to recognise that most patients with PTSD do not reflect the clinical trial samples and do not fully recover with brief manualised therapies. Treatment guidelines should be developed that address the multiple needs and challenges of all patients with PTSD.
On the uses and abuses of narcissism as a public health issue
Authors: Freestone Mark , Osman Magda , Ibrahim Yasmin
Published: April 2020

Psychiatry understands narcissism as a pathological condition associated with poor social outcomes and difficulty relating to others. Millennials have been depicted by psychological research as ‘narcissistic’, and the term has lost accurate meaning. We underline the intellectual laxity of conflating social changes with narcissism and suggest ways forward.
Research into mental health supported accommodation – desperately needed but challenging to deliver
Authors: Killaspy Helen , Priebe Stefan
Published: April 2020

Around 100 000 people live in mental health supported accommodation in England, at considerable cost to the public purse, but there is little evidence to guide investment in the most effective models. We consider the various barriers to research in this field and offer suggestions on how to address them.
The Practical Application of Emerging Technologies Influencing the Diagnosis and Care of Patients With Primary Brain Tumors
Authors: Hu Leland S. , Brat Daniel J. , Bloch Orin , Ramkissoon Shakti , Lesser Glenn J.
Published: April 2020

Over the past decade, a variety of new and innovative technologies has led to important advances in the diagnosis and management of patients with primary malignant brain tumors. New approaches to surgical navigation and tumor localization, advanced imaging to define tumor biology and treatment response, and the widespread adoption of a molecularly defined integrated diagnostic paradigm that complements traditional histopathologic diagnosis continue to impact the day-to-day care of these patients. In the neuro-oncology clinic, discussions with patients about the role of tumor treating fields (TTFields) and the incorporation of next-generation sequencing (NGS) data into therapeutic decision-making are now a standard practice. This article summarizes newer applications of technology influencing the pathologic, neuroimaging, neurosurgical, and medical management of patients with malignant primary brain tumors.
Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial
Authors: Topalian Suzanne L. , Bhatia Shailender , Amin Asim , Kudchadkar Ragini R. , Sharfman William H. , Lebbé Celeste , Delord Jean-Pierre , Dunn Lara A. , Shinohara Michi M. , Kulikauskas Rima , Chung Christine H. , Martens Uwe M. , Ferris Robert L. , Stein Julie E. , Engle Elizabeth L. , Devriese Lot A. , Lao Christopher D. , Gu Junchen , Li Bin , Chen Tian , Barrows Adam , Horvath Andrea , Taube Janis M. , Nghiem Paul
Published: April 2020

PURPOSE

Merkel cell carcinoma (MCC) is a rare, aggressive skin cancer commonly driven by the Merkel cell polyomavirus (MCPyV). The programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) immunosuppressive pathway is often upregulated in MCC, and advanced metastatic MCC frequently responds to PD-1 blockade. We report what we believe to be the first trial of anti–PD-1 in the neoadjuvant setting for resectable MCC.

METHODS

In the phase I/II CheckMate 358 study of virus-associated cancer types, patients with resectable MCC received nivolumab 240 mg intravenously on days 1 and 15. Surgery was planned on day 29. Tumor regression was assessed radiographically and microscopically. Tumor MCPyV status, PD-L1 expression, and tumor mutational burden (TMB) were assessed in pretreatment tumor biopsies.

RESULTS

Thirty-nine patients with American Joint Committee on Cancer stage IIA-IV resectable MCC received ≥ 1 nivolumab dose. Three patients (7.7%) did not undergo surgery because of tumor progression (n = 1) or adverse events (n = 2). Any-grade treatment-related adverse events occurred in 18 patients (46.2%), and grade 3-4 events in 3 patients (7.7%), with no unexpected toxicities. Among 36 patients who underwent surgery, 17 (47.2%) achieved a pathologic complete response (pCR). Among 33 radiographically evaluable patients who underwent surgery, 18 (54.5%) had tumor reductions ≥ 30%. Responses were observed regardless of tumor MCPyV, PD-L1, or TMB status. At a median follow-up of 20.3 months, median recurrence-free survival (RFS) and overall survival were not reached. RFS significantly correlated with pCR and radiographic response at the time of surgery. No patient with a pCR had tumor relapse during observation.

CONCLUSION

Nivolumab administered approximately 4 weeks before surgery in MCC was generally tolerable and induced pCRs and radiographic tumor regressions in approximately one half of treated patients. These early markers of response significantly predicted improved RFS. Additional investigation of these promising findings is warranted.
LncRNA-Malat1 is Involved in Lipotoxicity-Induced ß-cell Dysfunction and the Therapeutic Effect of Exendin-4 via Ptbp1
Authors: Xiong Li , Gong Yingying , Wu Liting , Li Jin , He Weiman , Zhu Xiaonan , Xiao Haipeng
Published: April 2020

Increasing evidence indicates that long noncoding RNAs (lncRNAs) have crucial roles in various biological processes. However, the contribution of lncRNAs to β-cell dysfunction and their roles in diabetes therapeutics remain poorly understood. The aim of this study was to identify the lncRNAs dysregulated in diabetic islets and to explore the lncRNAs involved in β-cell function as potential therapeutic targets. By using RNA sequencing and real-time PCR, we identified thousands of lncRNAs in the islets of db/db mice and db/m littermate mice. Among the differentially expressed lncRNAs, lncRNA-Malat1 (metastasis-associated lung adenocarcinoma transcript 1) was reduced in the islets of db/db mice and palmitate-treated MIN6 cells. The results of TUNEL, Western blot and flow cytometric analyses, and GSIS assays revealed that Malat1 knockdown significantly induced β-cell apoptosis and inhibited insulin secretion. Mechanistically, RNA immunoprecipitation showed that Malat1 enhanced polypyrimidine tract-binding protein 1 (Ptbp1) protein stability by direct interaction, thereby adjusting the ratio of pyruvate kinase muscle (PKM) isoforms 1 and 2 (PKM1/PKM2). Moreover, luciferase assay and chromatin immunoprecipitation indicated that Malat1 was transcriptionally activated by pancreatic and duodenal homeobox 1 (Pdx1), through which exendin-4 alleviated lipotoxicity-induced β-cell damage. In summary, our findings suggested the involvement of Malat1 in β-cell dysfunction under diabetic conditions via the Malat1/Ptbp1/PKM2 pathway. In addition, exendin-4 ameliorated β-cell impairment by Pdx1-mediated Malat1 upregulation. Hence, Malat1 may serve as a therapeutic target for the treatment of type 2 diabetes.
Pectoral Nerve Block Type II as the Sole Anesthetic for Removal of a Large Axillary Tumor: A Case Report
Authors: Van de Putte Peter , Blockmans Diederik , De Rop Carine , Versyck Barbara
Published: April 2020

The pectoral nerve block type II (Pecs II block) combined with general anesthesia provides analgesia during breast and axillary surgery. This report describes the first use of the Pecs II block as the sole anesthetic for axillary surgery. A patient needed resection of axillary masses. She was not only very reluctant to have general anesthesia but also considered high risk because of multiple comorbidities. An ultrasound-guided Pecs II block was performed. Both masses were resected without additional sedation or analgesia. This case report suggests that, in selected cases, the Pecs II block can be used as the sole anesthetic for axillary surgery.
Anesthetic Management for a Patient With MECP2 Duplication Syndrome: A Case Report
Authors: Choi Yuen-Ling Janíce , Wong Tsz-Kin Marcus , Ng Kwok Keung Daniel
Published: April 2020

Methyl CpG binding protein 2 (MECP2) duplication syndrome is a rare X-linked genetic disease. Core phenotypes include infantile hypotonia, developmental delay, and minimal speech with mild dysmorphic features. Many have refractory epilepsy and recurrent infections, which are the leading causes of mortality. This article presents a case of a patient with MECP2 duplication syndrome who required general anesthesia for respiratory workup and reviews the anesthetic management for these patients, which includes induction technique, choice of drugs, and other major anesthetic concerns.
Successful Combination of Neuraxial and Regional Anesthesia in a Child With Advanced Spinal Muscular Atrophy Type 1 Receiving Maintenance Nusinersen Therapy: A Case Report
Authors: Brown Alison F. , Einhorn Lisa M.
Published: April 2020

Spinal muscular atrophy (SMA) is an autosomal recessive condition characterized by degeneration of the anterior horn cells of the spinal cord, which causes progressive muscle atrophy and weakness. SMA type 1 is the most common type and is associated with severe disability and early mortality. Concomitant restrictive respiratory physiology often manifests with significant implications for anesthetic management. Here, we describe a successful spinal anesthetic for orthopedic surgery in an SMA type 1 patient receiving intrathecal nusinersen maintenance therapy, an antisense oligonucleotide designed to increase expression of the survival motor neuron protein, and the first US Food and Drug Administration–approved drug to treat SMA.
An Old Materialism
Authors: Wolf Johannes
Published: April 2020

This article takes a new approach to the conflicts represented in the thirteenth- century saints’ lives of the Katherine Group. Identifying saints and idols as contrasting poles in these conflicts, it argues that the category of sentience is a key distinguisher that is consistently employed to denigrate idols and idolators. Pagan antagonists are systematically identified as nonagential and material; by contrast, the saints communicate divine truth unimpeded and resist attempts to disrupt their highly integrated performances. The category of sentience is shuttled to-and-fro between parties as various antagonists attempt to reduce the saint to the status of an object. While superficially victorious, the saints finally fall prey to the binary logic of hagiography: to triumph over interrogation, torture, and death, the saint ultimately sacrifices her own sentience. This analysis reveals the investments of a medieval theory of sentience with implications for both hagiography at large and the twenty-first-century material turn.
Survivors of Witch Trials and the Quest for Justice in Early Modern Germany
Authors: Jütte Daniel
Published: April 2020

This article explores the trauma that early modern witchcraft trials inflicted on survivors and their communities. The point of departure is the case of Margareth Los, a widow accused of witchcraft in 1520s Württemberg. Subjected to brutal torture, Los was acquitted provisionally after three years in jail. Remarkably, she had the strength to produce an account of her ordeal and to bring her case before the highest court of justice in the Empire. The historical literature on witch trials has long been polarized by the quest for the most “accurate” death tolls. However, the social cost of witch hunts cannot be assessed by the number of death sentences alone. As Los’s case illustrates, witch hunts often had inconclusive outcomes, leaving the accused in a legal limbo that could last for years or even decades. Only one outcome was always the same: witch trials left behind a population of uprooted, dispossessed, and traumatized individuals.
“A wife or friend at e’ery Port”
Authors: Ellinghausen Laurie
Published: April 2020

The “sailor ballads” of the early British Empire employ popular song not only to investigate sailors’ hardships and victories, but to explore the character attributes of seafaring men. This article argues that the range of attitudes and concerns present in these texts signals a larger cultural conversation about these men’s fitness as husbands to the nation’s women, fathers to its children, and members of its communities. Although protoimperialist and mercantilist writers such as John Dee, Robert Hitchcock, and Edward Misselden stressed the social benefits of employing common men in large-scale seafaring projects, the ballads explore the consequences of the common sailor’s presence—and most particularly, his prolonged absence—on the traditional stabilizing structures of family and community. In doing so, the ballads critically examine the potential rewards and consequences of imperial expansion from a terrestrial, local, and communal perspective.
Osh6 requires Ist2 for localization to ER–PM contacts and efficient phosphatidylserine transport in budding yeast
Authors: D'Ambrosio Juan Martín , Albanèse Véronique , Lipp Nicolas-Frédéric , Fleuriot Lucile , Debayle Delphine , Drin Guillaume , Čopič Alenka
Published: April 2020

Osh6 and Osh7 are lipid transfer proteins (LTPs) that move phosphatidylserine (PS) from the endoplasmic reticulum (ER) to the plasma membrane (PM). High PS levels at the PM are key for many cellular functions. Intriguingly, Osh6 and Osh7 localize to ER–PM contact sites, although they lack membrane-targeting motifs, in contrast to multidomain LTPs that both bridge membranes and convey lipids. We show that Osh6 localization to contact sites depends on its interaction with the cytosolic tail of the ER–PM tether Ist2, a homolog of TMEM16 proteins. We identify a motif in the Ist2 tail, conserved in yeasts, as the Osh6-binding region, and we map an Ist2-binding surface on Osh6. Mutations in the Ist2 tail phenocopy osh6Δ osh7Δ deletion: they decrease cellular PS levels and block PS transport to the PM. Our study unveils an unexpected partnership between a TMEM16-like protein and a soluble LTP, which together mediate lipid transport at contact sites.

This article has an associated First Person interview with the first author of the paper.
Seeing the rainbow: mechanisms underlying spectral sensitivity in teleost fishes
Authors: Carleton Karen L. , Escobar-Camacho Daniel , Stieb Sara M. , Cortesi Fabio , Marshall N. Justin
Published: April 2020

Among vertebrates, teleost eye diversity exceeds that found in all other groups. Their spectral sensitivities range from ultraviolet to red, and the number of visual pigments varies from 1 to over 40. This variation is correlated with the different ecologies and life histories of fish species, including their variable aquatic habitats: murky lakes, clear oceans, deep seas and turbulent rivers. These ecotopes often change with the season, but fish may also migrate between ecotopes diurnally, seasonally or ontogenetically. To survive in these variable light habitats, fish visual systems have evolved a suite of mechanisms that modulate spectral sensitivities on a range of timescales. These mechanisms include: (1) optical media that filter light, (2) variations in photoreceptor type and size to vary absorbance and sensitivity, and (3) changes in photoreceptor visual pigments to optimize peak sensitivity. The visual pigment changes can result from changes in chromophore or changes to the opsin. Opsin variation results from changes in opsin sequence, opsin expression or co-expression, and opsin gene duplications and losses. Here, we review visual diversity in a number of teleost groups where the structural and molecular mechanisms underlying their spectral sensitivities have been relatively well determined. Although we document considerable variability, this alone does not imply functional difference per se. We therefore highlight the need for more studies that examine species with known sensitivity differences, emphasizing behavioral experiments to test whether such differences actually matter in the execution of visual tasks that are relevant to the fish.
Hourly 4-s Sprints Prevent Impairment of Postprandial Fat Metabolism from Inactivity
Authors: WOLFE ANTHONY S. , BURTON HEATH M. , VARDARLI EMRE , COYLE EDWARD F.
Published: April 2020

High postprandial plasma lipids (PPL; i.e., triglycerides) are a risk factor for cardiovascular disease. Physical inactivity, characterized by prolonged sitting and a low step count, elevates PPL and thus risk of disease.

Purpose

This study determined if the interruption of prolonged sitting (i.e., 8 h of inactivity) with hourly cycling sprints of only 4-s duration each (i.e., 4 s × 5 per hour × 8 h = 160 s·d−1 SPRINTS) improves PPL. The 4-s sprints used an inertial load ergometer and were followed by 45 s of seated rest.

Methods

Four men and four women participated in two trials. Interventions consisted of an 8-h period of sitting (SIT), or a trial with equal sitting time interrupted with five SPRINTS every hour. The morning after the interventions, PPL and fat oxidation were measured over a 6-h period. Plasma glucose, insulin, and triglyceride concentrations were measured bihourly and incremental area under the curve (AUC) was calculated.

Results

No differences (P > 0.05) between interventions were found for plasma insulin or glucose AUC. However, SPRINTS displayed a 31% (408 ± 119 vs 593 ± 88 mg·dL−1 per 6 h; P = 0.009) decrease in plasma triglyceride incremental AUC and a 43% increase in whole-body fat oxidation (P = 0.001) when compared with SIT.

Conclusions

These data indicate that hourly very short bouts (4 s) of maximal intensity cycle sprints interrupting prolonged sitting can significantly lower the next day’s postprandial plasma triglyceride response and increase fat oxidation after a high-fat meal in healthy young adults. Given that these improvements were elicited from only 160 s of nonfatiguing exercise per day, it raises the question as to what is the least amount of exercise that can acutely improve fat metabolism and other aspects of health.
Exercise Training Impacts Skeletal Muscle Clock Machinery in Prediabetes
Authors: ERICKSON MELISSA L. , ZHANG HUI , MEY JACOB T. , KIRWAN JOHN P.
Published: April 2020

Purpose

Disruption of the skeletal muscle molecular clock leads to metabolic disease, whereas exercise may be restorative, leading to improvements in metabolic health. The purpose of this study was to evaluate the effects of a 12-wk exercise intervention on skeletal muscle molecular clock machinery in adults with obesity and prediabetes, and determine whether these changes were related to exercise-induced improvements in metabolic health.

Methods

Twenty-six adults (age, 66 ± 4.5 yr; body mass index (BMI), 34 ± 3.4 kg·m−2; fasting plasma glucose, 105 ± 15 mg·dL−1) participated in a 12-wk exercise intervention and were fully provided isoenergetic diets. Body composition (dual x-ray absorptiometry), abdominal adiposity (computed tomography scans), peripheral insulin sensitivity (euglycemic–hyperinsulinemic clamp), exercise capacity (maximal oxygen consumption), and skeletal muscle molecular clock machinery (vastus lateralis biopsy) were assessed at baseline and after intervention. Gene and protein expression of skeletal muscle BMAL1, CLOCK, CRY1/2, and PER 1/2 were measured by quantitative real-time polymerase chain reaction and Western blot, respectively.

Results

Body composition (BMI, dual x-ray absorptiometry, computed tomography), peripheral insulin sensitivity (glucose disposal rate), and exercise capacity (maximal oxygen consumption) all improved (P < 0.005) with exercise training. Skeletal muscle BMAL1 gene (fold change, 1.62 ± 1.01; P = 0.027) and PER2 protein expression (fold change, 1.35 ± 0.05; P = 0.02) increased, whereas CLOCK, CRY1/2, and PER1 were unchanged. The fold change in BMAL1 correlated with post–glucose disposal rate (r = 0.43, P = 0.044), BMI (r = −0.44, P = 0.042), and body weight changes (r = −0.44, P = 0.039) expressed as percent delta.

Conclusions

Exercise training impacts skeletal muscle molecular clock machinery in a clinically relevant cohort of adults with obesity and prediabetes. Skeletal muscle BMAL1 gene expression may improve insulin sensitivity. Future studies are needed to determine the physiological significance of exercise-induced alterations in skeletal muscle clock machinery.
Microvascular Function Is Impaired after Short-Term Immobilization in Healthy Men
Authors: RYTTER NICOLAI , PIIL PETER , CARTER HOWARD , NYBERG MICHAEL , HELLSTEN YLVA , GLIEMANN LASSE
Published: April 2020

Purpose

We examined whether 2 wk of one-leg immobilization would impair leg microvascular function and to what extent a subsequent period of intense aerobic cycle training could restore function.

Methods

Study participants were healthy young men (n = 12; 20–24 yr of age). Leg microvascular function was determined before the intervention, after the immobilization period, and after a 4-wk exercise training period. Microvascular function was assessed as the vasodilator response to intra-arterial infusion of acetylcholine and sodium nitroprusside and as the vasoconstrictor response to endogenous noradrenaline release induced by tyramine infusion. Vasodilator enzymes as well as prooxidant and antioxidant enzymes were assessed by protein analysis in skeletal muscle samples: endothelial nitric oxide synthase, NADPH oxidase (NOX p67phox and NOX gp91phox), and superoxide dismutase 2 (SOD2).

Results

The acetylcholine-induced change in vascular conductance was reduced after the 2 wk of immobilization (P = 0.003), tended to increase (P = 0.061), and was back to baseline levels after the subsequent 4 wk of exercise training. Plasma prostacyclin levels in response to acetylcholine infusion were lower after immobilization than before (P = 0.041). The changes in vascular conductance with sodium nitroprusside and tyramine were similar during all conditions. Skeletal muscle protein levels of endothelial nitric oxide synthase in the experimental leg were unchanged with immobilization and subsequent training but increased 47% in the control leg with training (P = 0.002). NOX p67phox, NOX gp91phox, and SOD2 in the experimental leg remained unaltered with immobilization, and SOD2 was higher than preimmobilization after 4 wk of training (P < 0.001).

Conclusions

The study shows that 2 wk of immobilization impairs leg microvascular endothelial function and prostacyclin formation but that 4 wk of intense aerobic exercise training restores the function. The underlying mechanism may reside in the prostacyclin system.
Muscle Metabolism and Fatigue during Simulated Ice Hockey Match-Play in Elite Players
Authors: VIGH-LARSEN JEPPE F. , ERMIDIS GEORGIOS , RAGO VINCENZO , RANDERS MORTEN B. , FRANSSON DAN , NIELSEN JAKOB L. , GLIEMANN LASSE , PIIL JACOB F. , MORRIS NATHAN B. , DE PAOLI FRANK V. , OVERGAARD KRISTIAN , ANDERSEN THOMAS B. , NYBO LARS , KRUSTRUP PETER , MOHR MAGNI
Published: April 2020

Purpose

The present study investigated muscle metabolism and fatigue during simulated elite male ice hockey match-play.

Methods

Thirty U20 male national team players completed an experimental game comprising three periods of 8 × 1-min shifts separated by 2-min recovery intervals. Two vastus lateralis biopsies were obtained either during the game (n = 7) or pregame and postgame (n = 6). Venous blood samples were drawn pregame and at the end of the first and last periods (n = 14). Activity pattern and physiological responses were continuously monitored using local positioning system and heart rate recordings. Further, repeated-sprint ability was tested pregame and after each period.

Results

Total distance covered was 5980 ± 199 m with almost half the distance covered at high skating speeds (>17 km·h−1). Average and peak on-ice heart rate was 84% ± 2% and 97% ± 2% of maximum heart rate, respectively. Muscle lactate increased (P ≤ 0.05) more than fivefold and threefold, whereas muscle pH decreased (P ≤ 0.05) from 7.31 ± 0.04 pregame to 6.99 ± 0.07 and 7.13 ± 0.11 during the first and last periods, respectively. Muscle glycogen decreased by 53% postgame (P ≤ 0.05) with ~65% of fast- and slow-twitch fibers depleted of glycogen. Blood lactate increased sixfold (P ≤ 0.05), whereas plasma free fatty acid levels increased 1.5-fold and threefold (P ≤ 0.05) after the first and last periods. Repeated-sprint ability was impaired (~3%; P ≤ 0.05) postgame concomitant with a ~10% decrease in the number of accelerations and decelerations during the second and last periods (P ≤ 0.05).

Conclusions

Our findings demonstrate that a simulated ice hockey match-play scenario encompasses a high on-ice heart rate response and glycolytic loading resulting in a marked degradation of muscle glycogen, particularly in specific sub-groups of fibers. This may be of importance both for fatigue in the final stages of a game and for subsequent recovery.
Exercise Training Improves Microvascular Function in Burn Injury Survivors
Authors: ROMERO STEVEN A. , MORALEZ GILBERT , JAFFERY MANALL F. , HUANG MU , ENGELLAND RACHEL E. , CRAMER MATTHEW N. , CRANDALL CRAIG G.
Published: April 2020

Introduction

Vasodilator function is impaired in individuals with well-healed burn injuries; however, therapeutic interventions that lessen or reverse this maladaptation are lacking. The purpose of this study was to test the hypothesis that a 6-month community-based exercise training program would increase microvascular dilator function in individuals with well-healed burn injuries, irrespective of the magnitude of the injured body surface area. Further, we hypothesize that macrovascular dilator function would remain unchanged posttraining.

Methods

Microvascular function (forearm reactive hyperemia), macrovascular function (brachial artery flow-mediated dilation), and the maximal vasodilatory response after ischemic handgrip exercise (an estimate of microvascular remodeling) were assessed before and after exercise training in nonburned control subjects (n = 11) and individuals with burn injuries covering a moderate body surface area (26% ± 7%; n = 13) and a high body surface area (59% ± 15%; n = 19).

Results

Peak vascular conductance and area under the curve during postocclusive reactive hyperemia increased from pretraining to posttraining in control and burn injury groups (both P < 0.05), the magnitude of which did not differ between groups (both P = 0.6). Likewise, the maximal vasodilatory response after ischemic handgrip exercise increased in all groups after exercise training (P < 0.05). Macrovascular dilator function did not differ across time or between groups (P = 0.8).

Conclusions

These data suggest that a community-based exercise training program improves microvascular function in individuals with well-healed burn injuries, which may be due in part to vascular remodeling.