bluuebunny/crossref_metadata_2025 huggingface dataset:
The Nation-State: Not Yet Ready For the Dustbin of History?
Authors: Müllerson Rein
Published: November 2021

At the turn of the millennia, the ideas of withering away of the Nation-State became, once again, widespread. The latest wave of globalisation was supposed to lead to a borderless world, where goods, money, capital and workforce would move without hindrance. Multinational companies, non-governmental organisations (NGOs), big cities, regions (e.g., California or Bavaria), supranational entities, like the European Union, and even individuals would replace States as important decision-makers. This should have also been a triumph of liberal-democracy and the end of history à la Francis Fukuyama. This was also meant to be an American century where the only remaining superpower would lead the world either by example, by persuasion, or, if necessary, by punishing those who disobeyed. However, this was not to be the case. Excesses of globalisation, marked by financial and economic crises, the arrogant and naïve triumphalism of the West that attempted to remake the world in accordance with its own image, often using military power to carry out regime change, soon made it clear that the world is too big, complex and diverse to have its rich tapestry to be flattened into a carpet where only one pattern, be it of a Judeo-Christian, Anglo-Saxon, Confucian, Muslim or even secular liberal-democratic, would dominate. Moreover, the Nation-State, as a cradle of democracy and the main subject of international law, has made its comeback even in the Old Continent where it had emerged and was meant to make way for more progressive political arrangements. In places where the State authority was weakened or had collapsed, often as a result of foreign interference, chaos reigned instead of democracy and attempts to replace international law with imperial rule failed. It is becoming more and more obvious that democracy can be restored and reinforced by strengthening Statehood, not weakening it, and peace can be best guaranteed by balance of power between sovereign States cooperating with each other notwithstanding differences in their domestic arrangements.
Pharmacogenetics of the Late-Onset Efavirenz Neurotoxicity Syndrome (LENS)
Authors: van Rensburg Roland , Nightingale Sam , Brey Naeem , Albertyn Christine H , Kellermann Tracy A , Taljaard Jantjie J , Esterhuizen Tonya M , Sinxadi Phumla Z , Decloedt Eric H
Published: November 2021

Background

The late-onset efavirenz neurotoxicity syndrome (LENS) presents as ataxia and/or encephalopathy with supratherapeutic efavirenz plasma concentrations (>4 µg/mL). Efavirenz is primarily metabolized by cytochrome P450 2B6 (CYP2B6), with CYP2A6 as an accessory pathway. We hypothesized that participants with LENS would predominantly be CYP2B6 slow metabolizers. The aim of our study was to determine the frequency of CYP2B6 slow metabolizers in participants with LENS.

Methods

Adult HIV-positive participants on efavirenz-based antiretroviral therapy presenting with LENS were prospectively enrolled. Genetic polymorphisms known to be associated with increased efavirenz plasma concentrations in CYP2B6 (rs3745274, rs28399499, rs4803419) and CYP2A6 (rs28399433) were selected and used to determine proportions of slow metabolizers. Pharmacokinetic analyses were performed using liquid chromatography–tandem mass spectrometry. Median (IQR) plasma efavirenz and 8-hydroxyefavirenz were described.

Results

Fifteen participants were enrolled. Thirteen (13/15) were Black-African and 13 were female. Median weight was 49.9kg with a median duration on efavirenz of 2.2 years. All 15 participants were successfully genotyped as slow CYP2B6 metabolizers, with 6 participants additionally having CYP2A6 heterozygous genotype. Thirteen were receiving the CYP2A6 enzyme inhibitor isoniazid, and all 15 were genotypic NAT2 slow or intermediate acetylators. Efavirenz plasma concentration was markedly increased at 50.5 (47.0–65.4) µg/mL; 8-hydroxyefavirenz concentration was markedly decreased at 0.10 (0.07–0.15) µg/mL.

Conclusions

Our cohort provides definitive evidence that LENS is associated with the CYP2B6 slow metabolizer genotype, with a median efavirenz plasma concentration >12-fold higher than the defined upper limit of the therapeutic range. Isoniazid and low body weight are important contributors to LENS development.
Metformin induces lactate accumulation and accelerates renal cyst progression in Pkd1-deficient mice
Authors: Chang Ming-Yang , Tsai Chung-Ying , Chou Li-Fang , Hsu Shen-Hsing , Yang Huang-Yu , Hung Cheng-Chieh , Tian Ya-Chung , Ong Albert C M , Yang Chih-Wei
Published: November 2021

Metabolic reprogramming is a potential treatment strategy for autosomal dominant polycystic kidney disease (ADPKD). Metformin has been shown to inhibit the early stages of cyst formation in animal models. However, metformin can lead to lactic acidosis in diabetic patients with advanced chronic kidney disease, and its efficacy in ADPKD is still not fully understood. Here, we investigated the effect of metformin in an established hypomorphic mouse model of PKD that presents stable and heritable knockdown of Pkd1. The Pkd1 miRNA transgenic mice of both genders were randomized to receive metformin or saline injections. Metformin was administrated through daily intraperitoneal injection from postnatal day 35 for 4 weeks. Unexpectedly, metformin treatment at a concentration of 150 mg/kg increased disease severity, including kidney-to-body weight ratio, cystic index and plasma BUN levels, and was associated with increased renal tubular cell proliferation and plasma lactate levels. Functional enrichment analysis for cDNA microarrays from kidney samples revealed significant enrichment of several pro-proliferative pathways including β-catenin, hypoxia-inducible factor-1α, protein kinase Cα and Notch signaling pathways in the metformin-treated mutant mice. The plasma metformin concentrations were still within the recommended therapeutic range for type 2 diabetic patients. Short-term metformin treatment in a second Pkd1 hypomorphic model (Pkd1RC/RC) was however neutral. These results demonstrate that metformin may exacerbate late-stage cyst growth associated with the activation of lactate-related signaling pathways in Pkd1 deficiency. Our findings indicate that using metformin in the later stage of ADPKD might accelerate disease progression and call for the cautious use of metformin in these patients.
Something Ventured, Nothing Gained?—Remedies before the ECtHR and Their Potential for Climate Change Cases
Authors: Keller Helen , Heri Corina , Piskóty Réka
Published: November 2021

The European Court of Human Rights stands before what may be its greatest challenge: addressing current and impending human rights violations stemming from climate change. As the first climate cases trickle into the Court’s docket, and speculation about the Court’s response grows, many questions remain to be answered. Perhaps the matter of greatest uncertainty relates to the type and degree of redress that the Court can offer in this context. This article argues that the Court’s often deferential, inconsistent and unreasoned remedial practice is in urgent need of overhaul. It studies the Court’s remedial practice in environmental cases to draw conclusions about the Court’s existing approach to remedies and its self-perception in this context, i.e. its own understanding of the possibilities and limitations of its role. From this, it extrapolates the remedial approaches that could potentially be taken in climate cases, and discusses the advantages and disadvantages of each one.
Retrospective modelling of hospital bed capacities associated with the administration of remdesivir during the first wave of COVID-19 in a German metropolitan city
Authors: Jeck Julia , Jakobs Florian , Kron Anna , Cornely Oliver A , Kron Florian
Published: November 2021

Objectives

Internationally, healthcare systems are confronted by an ever-increasing scarcity of medical resources due to the ongoing novel coronavirus disease 2019 (COVID-19) pandemic. The aim of this study was to investigate the impact of remdesivir on the demand of hospital bed capacities for hospitalized COVID-19 patients and to evaluate the potentially created capacities for treating additional COVID-19 patients or elective treatments at the hospital.

Methods

An epidemiological model was developed that utilized the population of Cologne (Germany) during the first COVID-19 wave (first hospitalized patient—30 September 2020) to compare two scenarios: no administration of remdesivir (A) and the administration of remdesivir according to the EMA label (B). The results of the Adaptive COVID-19 Treatment Trial were used to evaluate the potential impact of remdesivir on hospital capacity.

Results

With the first recorded patient on 2 March 2020, a total of 576 COVID-19 hospitalized patients were detected during the first wave in Cologne. Comparing both scenarios (A versus B) of the model, the administration of remdesivir increased the number of discharges from 259 to 293 (+5.8%) and fewer patients needed ICU admission [214 versus 178 (−6.3%)]. In addition, the model estimated 20 fewer deaths (scenario B). Based on a reduced length of stay, 31.4 hospital beds (57.0 versus 25.6) could have been freed by administering remdesivir to eligible patients. This would have allowed either the treatment of an additional 730 COVID-19 patients or 660 elective treatments.

Conclusions

In our model, remdesivir administration profoundly contributed to free hospital capacities in the metropolitan city Cologne in Germany.
Predicting Phenology of Four Major Hemipteran Pests to Enhance Integrated Pest Management Programs in Potatoes in the Lower Columbia Basin
Authors: Oppedisano Tiziana , Shrestha Govinda , Anderson Sarah , Thompson Ira D , Rondon Silvia I
Published: November 2021

The potato crop (Solanum tuberosum L.) is affected by various hemipteran insect pests including Circulifer tenellus Baker, Lygus spp., Myzus persicae Sulzer, and Macrosiphum euphorbiae Thomas. These pests can cause direct foliage damage or vector plant pathogens, and consequently reduce potato yield. Gaining insights into which factors have the greatest impact on seasonal population growth of insect pests is key for improving integrated pest management strategies. Moreover, abiotic and biotic cues such as temperature and crop growth stage can strongly influence insect population growth. Hence, the seasonal population dynamics of C. tenellus, Lygus spp., M. persicae, and M. euphorbiae, and temperature, were monitored weekly throughout potato growing seasons in commercial fields located in the lower Columbia Basin (USA). Using a multi-year dataset, we developed phenology models of each pest based on the accumulated degree days (DD) and potato days (PD). Temperature-mediated population growth models suggest that C. tenellus and Lygus spp. are the first of the pests to colonize the potato crop fields, with 90% of cumulative catch by 2,823 and 1,776 DD, respectively. In contrast, M. persicae and M. euphorbiae populations increased more gradually over the course of the season, with 90% cumulative catch by 5,590 and 5,047 DD, respectively. PD-mediated population growth models suggest that 50% of the populations of C. tenellus, Lygus spp., and M. persicae can be collected at potato tuber growth stage, while 50% of the M. euphorbiae population at tuber initiation stage. The results presented here will help in improving hemipteran potato pests’ management.
Use of Boilerplate Language in Regulatory Documents: Evidence from Environmental Impact Statements
Authors: Scott Tyler A , Marantz Nicholas , Ulibarri Nicola
Published: November 2021

Administrative procedures are intended to increase transparency and help agencies make better decisions. However, these requirements also increase agency workload. Understanding how public agencies satisfy procedural requirements is a critical facet of agency performance. This analysis focuses on the language used in Environmental Impact Statements (EISs) required by the US National Environmental Policy Act (NEPA)—specifically, the reuse of similar text within and between assessments. We synthesize theories of institutional isomorphism and bureaucratic coping to understand why text is reused, and consider the tradeoffs of this behavior. Using a national dataset of 1015 EISs published by 22 agencies from 2013 to 2020, we apply local document alignment (LDA) to measure how boilerplate language varies by agency, authors, project type, location, and consulting firm involvement. Latent order logistic and beta regression models applied to the LDA results show that text reuse primarily occurs where there is a clear substantive rationale for boilerplate language or where studies share authors or contract consulting firms. This indicates: (1) that agencies largely do not engage in pro forma compliance efforts; and (2) that while NEPA procedures are oriented around individual projects and decisions, cross-project learning and the narrowness—or breadth—of agencies’ project portfolios shape analytical routines and the relative tradeoffs of boilerplate text in policy analysis. This article adds to our theoretical understanding of agencies’ coping strategies in response to institutional pressures and makes a methodological contribution by demonstrating the application of text reuse measurement and information extraction methods in public administration research.
Developing the Theory of Pragmatic Public Management through Classic Grounded Theory Methodology
Authors: Hafer Joseph A
Published: November 2021

Public administration scholars argue that further research is needed to understand ordinary day-to-day behaviors of the traditional government agency in the era of inter-organization collaboration and governance, including reconciling traditional bureaucratic management theories with modern-day cross-sector governance theories. I answered this call by utilizing classic grounded theory methodology to discover and theorize the latent patterns of behavior of such an agency—the Pennsylvania Bureau of Forestry—via the perspective of public managers. The primary source of data was unstructured interviews with 55 district and assistant district managers from the Bureau, and two interviews with executive directors of statewide nonprofits that frequently engage with the districts. Following the systematic processes of classic grounded theory methodology, I developed a theory called the Theory of Pragmatic Public Management that consists of the core category of Mission-driven Management, its four sub-core categories (Balancing, Advocating Value, Adapting to Uncertainty, and Prudent Collaboration), and two contextual conditions in the form of organization dynamics that impact the system (Organizational Capacity and Organizational Discretion). The theory is a modifiable and transferable theory that entwines traditional intra-organization management and inter-organization collaborative public management behaviors and relies on pragmatist thought for additional conceptual integration. It informs existing public management research that focuses on the day-to-day behaviors of public managers and offers practical insights on public management in the contemporary era of governance.
The double-stranded RNA-binding protein, Staufen1, is an IRES-transacting factor regulating HIV-1 cap-independent translation initiation
Authors: Ramos Hade , Monette Anne , Niu Meijuan , Barrera Aldo , López-Ulloa Brenda , Fuentes Yazmín , Guizar Paola , Pino Karla , DesGroseillers Luc , Mouland Andrew J , López-Lastra Marcelo
Published: November 2021

Translation initiation of the viral genomic mRNA (vRNA) of human immunodeficiency virus-type 1 (HIV-1) can be mediated by a cap- or an internal ribosome entry site (IRES)-dependent mechanism. A previous report shows that Staufen1, a cellular double-stranded (ds) RNA-binding protein (RBP), binds to the 5’untranslated region (5′UTR) of the HIV-1 vRNA and promotes its cap-dependent translation. In this study, we now evaluate the role of Staufen1 as an HIV-1 IRES-transacting factor (ITAF). We first confirm that Staufen1 associates with both the HIV-1 vRNA and the Gag protein during HIV-1 replication. We found that in HIV-1-expressing cells, siRNA-mediated depletion of Staufen1 reduces HIV-1 vRNA translation. Using dual-luciferase bicistronic mRNAs, we show that the siRNA-mediated depletion and cDNA-mediated overexpression of Staufen1 acutely regulates HIV-1 IRES activity. Furthermore, we show that Staufen1-vRNA interaction is required for the enhancement of HIV-1 IRES activity. Interestingly, we find that only Staufen1 harboring an intact dsRNA-binding domain 3 (dsRBD3) rescues HIV-1 IRES activity in Staufen1 CRISPR-Cas9 gene edited cells. Finally, we show that the expression of Staufen1-dsRBD3 alone enhances HIV-1 IRES activity. This study provides evidence of a novel role for Staufen1 as an ITAF promoting HIV-1 vRNA IRES activity.
How Does the Strength of the Far Right Affect Ethnic Minority Political Behaviour?
Authors: Martin Nicole S
Published: November 2021

This article considers how the far right affects ethnic minority vote choice and party evaluations, using the case of the British National Party (BNP). Minorities were more likely to vote for Labour in 2010 where the BNP received more votes, and a quasi-experimental increase in the BNP’s salience also increased support for Labour. However, ethnic minority voters evaluated the Conservatives more positively when the BNP put forward a candidate or received more votes. The strength of the far right may mobilise and reinforce traditional partisan loyalties among minorities, while changing perceptions of traditionally unpopular—but mainstream—alternatives.
Nudging Emergency Department-Initiated Addiction Treatment
Authors: Butler Kelley , Chavez Tyler , Wakeman Sarah , Robertson Ted , Leifer Jessica , Barofsky Jeremy , Kao Lee-Sien , Lefkowitz Jaclyn , Dutta Sayon , Hayes Bryan , White Ben , Raja Ali , Martin Alister
Published: November 2021

Objectives

When initiated in the Emergency Department (ED), medication for addiction treatment (MAT) with buprenorphine improves outcomes, increases engagement in addiction treatment and decreases the use of inpatient addiction treatment services. Unfortunately, initiating MAT in the ED is not yet standard practice. We assessed the impact of the addition of a multipart behavioral science-based intervention to increase opioid use disorder (OUD)-related treatments prescribed in the ED.

Methods

Our ED initiated a campaign to help ED faculty obtain their DEA-X waiver required to prescribe buprenorphine. In parallel, we implemented 2 ED-initiated buprenorphine treatment pathways. We then conducted a two-stage qualitative process informed by behavioral science to identify key barriers to physician use of the MAT protocol. Using these insights, we developed 4 behavioral science-based interventions. To assess the impact of the interventions on the number of OUD-related treatments per day among patients meeting the inclusion criteria we compared the number of OUD-related treatments per day before versus after the interventions began using t tests. Then, in our primary model, we estimated the causal effect of the behavioral interventions using a regression discontinuity in time approach.

Results

Across the entire year study period, there is an increase in OUD-related treatment after the interventions begin, driven by greater use of ambulatory referral orders. The unadjusted mean difference in any OUD treatments per day pre- versus post-intervention increased by 0.80 (95% confidence interval [CI]: 0.04, 1.56; P = 0.039) whereas the number of ambulatory referral orders placed increased by 0.82 (95% CI: 0.48,1.16; P < 0.001). Using the 120-day study window and an ordinary least squares regression discontinuity in time model, the 4-part intervention increased the number of patients receiving any opioid treatment in the ED by 1.6 additional treatments per day (95% CI: 0.04, 3.19; P = 0.045).

Conclusions

To support our protocol and increase the provision of ED-MAT, we implemented 1 patient-facing and 3 provider-facing interventions rooted in behavioral science principles. Our results show that this pack of behavioral science interventions increased the likelihood that ED providers offer MAT to patients with OUD.
Radiologic Outcomes of Bilateral and Unilateral Perthes Disease: A Comparative Cohort Study
Authors: Singh Kumar A. , Guddattu Vasudeva , Shah Hitesh
Published: November 2021

Introduction:

This study was undertaken to compare the radiologic outcomes of bilateral and unilateral Perthes disease and also to evaluate the outcome of synchronous and metachronous bilateral Perthes disease.

Methods:

Of 353 children with Perthes disease followed up from presentation to healing during the last 10 years, 37 had bilateral involvement (11 synchronous and 26 metachronous onset). The radiologic outcomes of each hip of children with bilateral disease were compared with outcomes of 148 children with unilateral disease who were matched for age, sex, and treatment. Children with unilateral or bilateral diseases were treated with a proximal femoral varus derotation osteotomy if they fulfilled the criteria for surgery. The primary outcome measure was the shape of the femoral head at healing assessed by the Sphericity Deviation Score (SDS).

Results:

The children with bilateral disease were younger than those with unilateral disease (6.2 vs. 7.03 y; P<0.001), and they had a longer duration of the disease. All other characteristics of bilateral and unilateral cases were similar. The SDS values of unilateral and bilateral disease were comparable, as were the SDS of synchronous and metachronous bilateral disease. The effect of early surgery on the evolution of the disease in bilateral cases was similar to that reported in unilateral disease. The age of onset of the disease alone influenced the SDS in bilateral cases.

Conclusion:

The age at onset of the bilateral disease is lower, the duration of the disease longer than that of unilateral disease, but the disease outcome is similar.
Decrease in Residual Neurological Symptoms After Institutional Changes in Peripheral Nerve Block Use for Pediatric Knee Surgery
Authors: Xu Amy L. , Lee R. Jay
Published: November 2021

Background:

Peripheral nerve blocks (PNBs) have recently been associated with a higher incidence of complications than previously thought. We compared: (1) incidence of PNB-related residual neurological symptoms and (2) patient selection, operative practices, and anesthesia practices for pediatric knee surgery patients before and after changes in PNB administration at our institution.

Methods:

We compared data from pediatric patients who underwent knee surgery with PNBs from 2014 to 2016 (cohort 1; 100 patients) or 2017 to 2019 (cohort 2; 104 patients). Cohort 2 was treated after PNB administration was limited to a dedicated anesthesia block team at our institution. We usedttests and χ2tests, with an α level of 0.05.

Results:

The incidence of PNB-related neurological complications was lower in cohort 2 (0.96%;) than cohort 1 (6%) (P=0.045). The 1 complication in cohort 2 was numbness proximal to the knee. Cohort 1 had 5 cases of numbness proximal to the knee and 1 case of neuropathic pain upon palpation of the PNB site. The proportion of female patients was greater in cohort 2 (57%) than cohort 1 (36%) (P=0.01); age and body mass index did not differ between cohorts. In cohort 2, the mean operating time was longer, and tourniquets were used more frequently (both,P<0.01). A greater proportion of PNBs were performed by fellows in cohort 2 (67%) versus cohort 1 (55%) (P=0.01). A smaller proportion of PNBs were performed by residents in cohort 2 (6.9%) versus cohort 1 (16%) (P=0.01). The most common anatomic site for PNBs was the femoral nerve (51%) in cohort 1 and the saphenous nerve (51%) in cohort 2 (P<0.01).

Conclusions:

The incidence of PNB-related complications after pediatric knee surgery decreased significantly after institutional changes in the regulation of PNB use. This decrease may be explained by shifts toward more experienced providers administering PNBs and preference for more distal anatomic sites, suggesting ways other institutions may lower their PNB complication rates.

Level of Evidence:

Level III—retrospective prognostic study.
Effects of Omega-3 Fatty Acids on Chinese Patients with Cardiovascular Risk Factors: A Systematic Review and Meta-Analysis
Authors: Mei Zhu , Song Haixu , Tian Xiaoxiang , Liu Dan
Published: November 2021

Objective:

Fish oil (FO) contains omega-3 that inhibits inflammation and blood lipid metabolism, giving it a protective cardiovascular effect. Due to dietary habits, a majority of large-scale clinical trials examining FO and cardiovascular health have been conducted in the Caucasian populations. However, the effects of FO on cardiovascular inflammation indicators and blood lipid metabolism in the Chinese population remain unclear. This study aimed to perform a meta-analysis to elucidate the impact of FO on cardiovascular health in the Chinese population.

Methods:

Web searches were utilized to locate records of clinical trials related to cardiovascular health and consumption of FO capsules or fish containing omega-3 in several databases, including PubMed, Medline, Embase, Cochrane Library, CNKI, and ClinicalTrial.gov, etc. We obtained lipid metabolism and related proinflammatory markers as the study outcome. We used Review Manager 5.4 and Stata 16 for the statistical analysis. If the I
2 ≥ 30%, a random effects model was used, and if the I
2 < 30%, a fixed effects model was used.

Results:

Twenty eligible trials were shortlisted from >1000 records. The meta-analysis revealed that supplementation with eicosapentaenoic acid and docosahexaenoic acid reduced systolic blood pressure by 1.88  mmHg (95% CI: −4.97 to −1.20, P = 0.23), diastolic blood pressure by 0.86  mmHg (95% CI: −1.79 to 0.06, P = 0.07), fasting blood glucose by 0.05 mmol/L (95% CI: −0.16 to 0.06, P = 0.40), and low-density lipoprotein-cholesterol by 0.12  mmol/L (95% CI: −0.23 to −0.01, P = 0.04), when compared to placebo. However, these supplements increased high-density lipoprotein-cholesterol by 0.03  mmol/L (95% CI: 0.01 to 0.05, P < 0.001), when compared to placebo. Dose subgroup analyses examining total cholesterol found that the low-dose group (mean difference = −0.44, 95% CI: −0.55 to −0.34, P < 0.001) demonstrated the best results. Further, results from dose subgroup analyses showed that the all-dose group demonstrated a decrease in tumor necrosis factor (TNF-α) levels among the study subjects, when compared to other groups.

Conclusions:

Consumption of FO containing omega-3 fatty acids in the Chinese population can improve lipid metabolism and reduce levels of proinflammatory markers. Therefore, it is necessary to vigorously promote the benefits of consuming FO to prevent cardiovascular diseases throughout China.
The immunologic balance: three cases of rituximab-associated melanoma
Authors: Davidson Tara M. , Markovic Svetomir N. , Dimou Anastasios
Published: November 2021

Currently, there is no known clinical evidence that rituximab increases the rate of subsequent primary malignancies; however, some studies have raised the question of increased melanoma risk following rituximab treatment for non-Hodgkin lymphoma. We report three interesting cases of suspected rituximab-induced melanoma. We hypothesize that this association is secondary to rituximab-driven shifts in the immunologic balance. Based on these cases, it is possible that the number of post-rituximab melanoma cases is underreported. Further mechanistic research into individual cases and population-level studies are required to better define association and risk; however, given the increasing prevalence of oncologic and nononcologic rituximab use, awareness across all fields is essential.
Long Noncoding RNAs Testis Development Related Gene 1 Aggravates Transforming Growth Factor-β1–Induced Fibrogenesis and Inflammatory Response of Cardiac Fibroblasts Via miR-605-3p/Tumor Necrosis Factor Receptor Superfamily-21 Axis
Authors: Cheng Jinghua , Tang Yi , Cai Xiaomin , Gong Jianbin
Published: November 2021

Heart failure is mainly caused by a decline in the systolic function of the heart. Long noncoding RNAs are related to cardiac diseases. This study aimed to explore the effects of long noncoding RNAs testis development related gene 1 (TDRG1) on the fibrogenesis and inflammatory response of transforming growth factor-beta1 (TGF-β1)-stimulated human cardiac fibroblasts (HCFs). Levels of proinflammatory cytokines were evaluated by enzyme-linked immunosorbent assay. Reverse-transcription quantitative polymerase chain reaction was applied to reveal the expression levels of TDRG1, miR-605-3p, and tumor necrosis factor receptor superfamily (TNFRSF21). Western blot analysis was prepared to detect protein levels of TNFRSF21 and fibrosis-related genes. Luciferase reporter assay was conducted for confirming the interaction between miR-605-3p and TDRG1/TNFRSF21. We found that TGF-β1–stimulated HCFs showed high concentrations of proinflammatory cytokines and increased protein levels of fibrosis-related genes, suggesting the dysfunctions of TGF-β1–stimulated HCFs. In addition, TDRG1 was upregulated in TGF-β1–stimulated HCFs. We found that interfering with TDRG1 alleviated dysfunctions of TGF-β1–stimulated HCFs. Moreover, TDRG1 bound with miR-605-3p. MiR-605-3p exerted the antifibrogenic and anti-inflammatory effects in TGF-β1–treated HCFs. As a target gene of miR-605-3p, TNFRSF21 reversed the antifibrogenic and anti-inflammatory effects of TDRG1 knockdown in TGF-β1–treated HCFs. Overall, our study confirmed that TDRG1 aggravates fibrogenesis and inflammatory response in TGF-β1–treated HCFs via the miR-605-3p/TNFRSF21 axis.
Current Perspectives of the Use of Sodium–Glucose Transport-2 Inhibitors for Patients With Heart Failure and Chronic Kidney Disease
Authors: Vider Etty , Sapir Ravit , Mosseri Eli , Gavioli Elizabeth
Published: November 2021

Sodium–glucose cotransporter-2 inhibitors (SGLT-2 inhibitors) are a relatively new class of drugs approved for the treatment of type 2 diabetes. In 2021, the American College of Cardiology recommended the use of SGLT-2 inhibitors in patients with heart failure (HF), with or without type 2 diabetes, because of their morbidity and mortality benefits. The review provides an overview of the efficacy and safety of SGLT-2 inhibitors in HF and chronic kidney disease (CKD). We review the existing literature for SGLT-2 inhibitors by searching PubMed.gov using the keywords SGLT-2 inhibitors, HF, and CKD. A clinical treatment pathway is provided to help guide clinicians in choosing an SGLT-2 inhibitor for their patients with chronic HF and CKD.
The State of Diversity in Academic Plastic Surgery Faculty across North America
Authors: Chawla Sahil , Chawla Amey , Hussain Mehwish , Karimuddin Ahmer A. , Khosa Faisal
Published: November 2021

Background:

Gender and racial disparity is prevalent in all surgical subspecialties with women and racial groups historically underrepresented in academic plastic surgery. This study evaluated gender and racial profiles of academic plastic surgery faculty in North America and correlated both with research productivity and its effect on academic ranks of faculty in plastic surgery.

Methods:

In this cross-sectional study, we compiled a list of accredited medical schools that offer plastic surgery training for residency. Data were collected on demographics, academic rank, and research output using the Doximity, LinkedIn, and Scopus databases. Data analyses were performed with a Mann-Whitney U test and a Kruskal-Wallis test.

Results:

Women who were black, indigenous, and/or other color occupied only 6.25% of plastic surgery faculty leadership positions in North America. There are more women and underrepresented minorities in leadership positions in Canada, when compared with the USA, relative to each country’s demographic. In both countries, women and underrepresented minority plastic surgeons had fewer publications, citations, and years of active research. Interestingly, having women in leadership positions was associated with a higher number of women faculty members.

Conclusions:

Gender and racial disparity exist in academic plastic surgery in North America. Several changes are required in order for women and underrepresented minorities in medicine to have an equal chance at career advancement. Better representation and diverse leadership have the potential to bring about equity, diversity, and inclusion in academic plastic surgery.
Frontal Cranioplasty with Vascularized Split-iliac Crest Bone Flap
Authors: Baudoin Morgan E. , Palines Patrick A. , Stalder Mark W.
Published: November 2021

Defects of the frontal bone require thoughtful consideration of reconstructive material to satisfy the aesthetic and functional demands of the region, as well as the anatomic adjacency to the frontal sinus. Some cases may be further complicated by a suboptimal operative field due to prior radiation, reconstructive procedures, or infection. Vascularized bone offers an ideal option to successfully reconstruct bony defects in harsh wound beds. Here, we report the case of a 47-year-old man with adenoid cystic carcinoma who underwent secondary reconstruction of the frontal bone with a split-iliac crest bone flap based on the deep circumflex iliac artery. The patient’s course following an initial ablative procedure was complicated by recurrent periorbital cellulitis, radiation, and eventual recurrence of the malignancy. Reconstructive requirements included restoration of the superior orbital rim, cranialization of the frontal sinus, and reconstruction of a sizeable frontal bone defect. In this setting, the iliac crest served as an excellent reconstructive option owing to its natural curvature and large surface area. The split-iliac crest deep circumflex iliac artery bone flap offers a robust and valuable reconstructive option for calvarial defects in hostile surgical fields.
Surgical Treatment of Intercostal Brachial Nerve Pain after Mastectomy and Axillary Dissection
Authors: Kim Justine S. , Spiess Alexander M.
Published: November 2021

Postmastectomy chronic pain describes chronic pain in the anterior aspect of the thorax, axilla, and/or upper half of the arm present after surgical treatment of breast cancer and persistent for more than 3 months. The most common cause of this syndrome is damage to the intercostal brachial nerve. Current methods of treatment include medications, physical therapy, and peripheral nerve blocks. The literature lacks data regarding surgical interventions for intercostal brachial nerve pain in the postmastectomy and axillary dissection breast cancer patient. We discuss a case of a 47-year-old woman with left breast cancer status post-nipple-sparing mastectomy and sentinel lymph node biopsy complicated by refractory dysesthesias in the intercostal brachial nerve distribution. Axillary exploration demonstrated a surgical clip with an associated neuroma of a branch of the intercostal brachial nerve. Excision and repair resulted in immediate pain relief in the postoperative period. We propose a comprehensive treatment algorithm to address postmastectomy pain attributed to intercostal brachial nerve pathology.
CHORIORETINAL ATROPHY IN VITREORETINAL LYMPHOMA
Authors: Marchese Alessandro , Cicinelli Maria VITTORIA , Cavalleri Michele , Bandello Francesco , Modorati Giulio , Miserocchi Elisabetta
Published: November 2021

Purpose:

To investigate the frequency, risk factors, and functional prognosis of chorioretinal atrophy (CRA) in vitreoretinal lymphoma (VRL).

Methods:

This was a retrospective cohort study of consecutive patients with vitreoretinal lymphoma. The demographic, clinical, and retinal features and the treatment modalities of each patient were collected. The charts and the multimodal imaging at each visit were reviewed. The risk factors associated with CRA were investigated with a mixed-model Cox regression.

Results:

Of the 79 eyes of 40 patients included, 41 eyes (52%) had CRA; 27 and 14 eyes had focal and diffuse CRA, respectively. The rate of vitreoretinal lymphoma lesions in the macula was similar between focal and diffuse CRA (96% vs. 93%). The eyes with CRA had worse best-corrected visual acuity (P = 0.006) than eyes with no CRA; diffuse atrophy had the worst best-corrected visual acuity (P < 0.001). The presence of retinal infiltrates (hazard ratio = 3.75, 95% confidence interval [CI] 1.46–9.59, P = 0.006) and vertical hyperreflective lesions (hazard ratio= 4.13 95% CI 1.14–14.93, P = 0.03) on optical coherence tomography and macular involvement (hazard ratio = 6.59, 95% CI 1.41–30.53, P = 0.02) were associated with a higher risk of CRA.

Conclusion:

Vitreoretinal lymphoma presenting with retinal infiltrates and macular involvement carried a higher risk of CRA. Risk factors for CRA should be identified for the potential of severe visual loss. Prompt diagnosis of vitreoretinal lymphoma may allow better control of the disease.
Total Anterior Staphyloma Secondary to Acanthamoeba Keratitis
Authors: Sachdev Amun , Sachdev Anshu , Mollan Susan P. , Snead David , Ahluwalia Harpreet S.
Published: November 2021

There are very few published cases of total anterior staphyloma, all of which have been reported as secondary to fungal keratitis. This study reports the clinical and histopathological findings and subsequent management of a 27-year-old healthy female patient who developed total anterior staphyloma after poor compliance with treatment for clinically diagnosed acanthamoeba keratitis. She underwent a successful evisceration with good long-term results. This case highlights that total anterior staphyloma may also result from untreated keratitis which is not fungal in origin. In cases of fungal and acanthamoeba keratitis, patient compliance with both treatment and follow-up is paramount to avoid vision-threatening sequelae that present significant challenges in their management.
Pediatric COVID-19 Therapeutics
Authors: Morin Sébastien , Lallemant Marc , Garcia-Prats Anthony , Lewis Linda , Watkins Melynda , Giaquinto Carlo , Valentin Marie , Penazzato Martina , Reeder John C.
Published: November 2021

Children, although at lower risk of poor outcomes from COVID-19 relative to adults, still stand to benefit from therapeutic interventions. Understanding of COVID-19 clinical presentation and prognosis in children is essential to optimize therapeutic trials design. This perspective illustrates how to collectively accelerate pediatric COVID-19 therapeutic research and development, based on the experience of the Global Accelerator for Paediatric Formulations.
Nimodipine in Clinical Practice: A Pharmacological Update
Authors: Clough Brendon , Tenii Josephine , Wee Claribel , Gunter Elizabeth , Griffin Tara , Aiyagari Venkatesh
Published: November 2021

INTRODUCTION: Enteral nimodipine provides a neuroprotective effect in patients who have experienced an aneurysmal subarachnoid hemorrhage (aSAH). Nimodipine remains the only US Food and Drug Administration–approved medication for aSAH. CONTENT: Nimodipine has been prescribed for patients with aSAH; however, little is known about factors to consider regarding dosing or patient-specific variables that may affect tolerability to nimodipine. Clinical impact of dose or dosing frequency changes has also been much debated based on risk of hypotension with currently approved dosing regimens. CONCLUSION: This review article addresses factors to consider for dosing and administration, pharmacokinetic and pharmacogenetic impact on nimodipine, and, finally, drug interaction considerations to assess as patients are initiated on enteral nimodipine for aSAH.
A Decade-long Comparison of Prestroke Health Behaviors Among Hypertensive Stroke Patients in Mainland China
Authors: Liu Qun-Hong , Tan Ju-Xiang , Hu Cai-Xia , Hu Dan-Lu , Wan Li-Hong
Published: November 2021

BACKGROUND: Patients with hypertension are at a high risk for stroke, but a healthy lifestyle can greatly reduce the risk of stroke. However, there has been no research on the change in prestroke health behaviors in Chinese patients with hypertensive stroke over a decade. OBJECTIVES: The aims of this study were to determine whether prestroke health behaviors of patients with hypertensive stroke changed over a decade and to explore the predictors of prestroke health behaviors over a decade. METHODS: This study used data from 2 cross-sectional studies conducted in the neurology departments of 3 hospitals in Guangzhou, China. In total, 110 hypertensive stroke patients were recruited in stage I (2008-2009), and 119 hypertensive stroke patients were recruited in stage II (2018-2019). Patients' stroke knowledge was measured by the Stroke Knowledge Questionnaire. Patients' prestroke health behavior was measured by the Health Behavior Scale for Stroke Patients. RESULTS: The total score of prestroke health behaviors significantly increased over the decade (P < .001), but the scores of the subcategories of low-fat diet, low-sugar diet, and blood pressure checkups decreased over the decade (P < .05). Stroke knowledge was a significant predictor of prestroke health behaviors in stage I (P < .05). Besides stroke knowledge, sex and age were significant predictors of prestroke health behaviors in stage II (P < .05). CONCLUSIONS: Prestroke health behaviors of hypertensive stroke patients significantly improved over the decade. Moreover, prestroke health behaviors were significantly influenced by stroke-related knowledge over the decade. Healthcare providers should focus in particular on assisting patients who are male, young, and middle-aged, and lack stroke-related knowledge to improve their prestroke health behaviors, especially in terms of adherence to a low-fat/low-sugar diet and regular blood pressure checks.
Effect of respiratory muscle training on expiratory muscle strength and abdominal electrical activity in the acute phase of Stroke
Authors: Sartor Lorena Cristina Alvarez , Luvizutto Gustavo José , Souza Juli Thomaz , Miranda Luana Aparecida , Molle da Costa Evelin Roberta Silva Dalle , Ribeiro Priscila Watson , Modolo Gabriel Pinheiro , da Silva Taís Regina , Prudente Robson Aparecido , Antunes Letícia Cláudia de Oliveira , da Costa Rafael Dalle Molle , Ferreira Natália Cristina , Nunes Hélio Rubens de Carvalho , Bazan Silméia Garcia Zanati , Winckler Fernanda Cristina , Minicucci Marcos Ferreira , Bazan Rodrigo
Published: November 2021

Background:

Respiratory muscle function can be compromised during the acute phase and this study aims to assess the effectiveness, feasibility, and safety of short-term expiratory muscle training in acute stroke patients. Additionally, we will assess the effects of expiratory muscular training on the electromyographic activity of the abdominal muscle, vital capacity, stroke severity, hand grip strength, functional independence, autonomy, and quality of life.

Methods:

This single-center, randomized, single-blind, parallel-group study of 88 patients with stroke will include the following groups: 1) an intervention group that will undergo expiratory muscle training, physical therapy, and standard care (n = 44) and 2) a control group that will only undergo physical therapy and standard care (n = 44). The primary outcome is respiratory muscle strength assessed via inspiratory and expiratory pressures (cmH2O). The secondary outcomes are electromyography activity of the rectus abdominis muscle and abdominal external oblique muscle, vital capacity measured by a ventilometer, handgrip strength, stroke severity and disability [National Institutes of Health Stroke Scale, modified Rankin Scale, and Barthel index], and quality of life. We will assess all variables before and after the intervention. The delta will be compared between the groups (intervention vs. control) using Student t-test for normal distribution and Mann-Whitney test for skewed distribution. The data will be analyzed using SPSS and results with P-values <.05 will be considered statistically significant.

Discussion:

The ACANTHUS trial has clinical relevance and is necessary since previous studies have revealed that respiratory rehabilitation after stroke improves patients’ functional capacities.

Trial Registration:

Registro Brasileiro de Ensaios Clínicos (Rebec) - RBR-8w44f6
Commonly used biomarkers do not contribute to diagnosing irritable bowel syndrome
Authors: Kramer Sjoerd , Masclee Ad A.M. , Jebbink Ric J.A. , Tack Greetje J.
Published: November 2021

Objective

The aim of this article was to examine the costs and effectiveness of standardized blood and fecal investigations in patients fulfilling the Rome criteria for irritable bowel syndrome (IBS).

Methods

We conducted a real-life cohort study in patients fulfilling the Rome III criteria for IBS without red flag signs or symptoms, in a center of excellence for IBS patients from 1 January 2015 till 1 January 2019. Standardized blood and fecal investigations [hemoglobin (Hb), thyroid-stimulating hormone (TSH), coeliac serology, and fecal calprotectin (FCP)] were performed during the first consultation. Patients were followed for at least 1 year. Primary outcome was the probability of another diagnosis than IBS with subsequent overall costs.

Results

A total of 218 patients were included. In approximately 200 patients blood and fecal investigations were performed and 47 patients underwent a colonoscopy. Two-hundred ten patients were diagnosed with IBS, 5 with inflammatory bowel disease (IBD), 1 with nonspecific acute ileitis, 1 with hyperthyroidism, and 1 with coeliac disease. The number needed to diagnose all included laboratory tests was 34, and for the individual test: TSH 197, coeliac serology 199, and FCP 50. The total costs were approximately €4900 to diagnose one patient with another diagnosis than IBS.

Conclusion

In our real-life cohort of adult patients under the age of 50 years fulfilling the Rome criteria for IBS without red flag symptoms, standardized blood, and fecal investigations have a very low diagnostic yield accompanied by high additional costs. Colonoscopy is not indicated in patients with Rome III positive IBS and normal FCP.