bluuebunny/crossref_metadata_2025 huggingface dataset:
Division of labour among culms in the clonal reedArundo donax(Poaceae) is underlain by their pre-determined hydraulic structure
Authors: Shtein Ilana , Baruchim Paz , Lev-Yadun Simcha
Published: June 2020

Clonal plants present an interesting example of division of labour among their ramets. Here we elaborated on hydraulic structure in respect to the division of labour among ramets in Arundo donax, a perennial clonal reed. Mature clones have three shoot types: (1) large mostly flowering; (2) medium mostly vegetative and (3) small vegetative. The shoots grow from buds initiating in the upper side of underground rhizomes, and the shoot growth is primary with vasculature produced from the procambium. We tested whether the number of vascular strands in a shoot has a fixed developmental programme or follows a flexible developmental pattern, and we found that the number of vascular strands strongly differs between shoot types. Large shoots on average have 560 vascular strands with both the widest vessels and significantly highest hydraulic conductivity. Medium ones and small shoots have 409 and 102 on average, respectively, with narrower vessels and with low conductivity. Thus, the shoot apices have three alternative developmental programmes. Apparently, a clone is built of functionally different modular units that enable Arundo donax to maximize its potential in a heterogeneous environment. Although the smaller culms do not contribute directly to the sexual reproduction of the clone, under stress their safer hydraulic system offers them a better chance of survival.
Drug-induced Liver Injury in a Patient With Coronavirus Disease 2019: Potential Interaction of Remdesivir With P-Glycoprotein Inhibitors
Authors: Leegwater Emiel , Strik Anne , Wilms Erik B , Bosma Liesbeth B E , Burger David M , Ottens Thomas H , van Nieuwkoop Cees
Published: June 2020

We report a case of a man with COVID-19 who developed acute hepatotoxicity related to remdesivir with probable interaction of P-glycoprotein (P-gp) inhibitors. Until further details on this interaction become available, we recommend physicians to be cautious with the prescription of P-gp inhibitors in patients receiving remdesivir therapy.
Slowly progressive anti-neutrophil cytoplasmic antibody-associated renal vasculitis: clinico-pathological characterization and outcome
Authors: Trivioli Giorgio , Gopaluni Seerapani , Urban Maria L. , Gianfreda Davide , Cassia Matthias A. , Vercelloni Paolo G. , Calatroni Marta , Bettiol Alessandra , Esposito Pasquale , Murtas Corrado , Alberici Federico , Maritati Federica , Manenti Lucio , Palmisano Alessandra , Emmi Giacomo , Romagnani Paola , Moroni Gabriella , Gregorini Gina , Sinico Renato A. , Jayne David R.W. , Vaglio Augusto
Published: June 2020

Background

Although rapidly progressive glomerulonephritis is the main renal phenotype of anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), slow renal disease progression is sometimes observed. These forms have been rarely discussed; we analysed their prevalence, clinico-pathological characteristics and outcome.

Methods

We screened patients with microscopic  polyangiitis (MPA) and granulomatosis with polyangiitis followed at seven referral centres and selected those with estimated glomerular filtration rate (eGFR) reduction <50% over a 6-month period preceding diagnosis. Data regarding patient features and response to treatment were retrieved.

Results

Of 856 patients, 41 (5%) had slowly progressive renal AAV. All had MPA and all but one was P-ANCA/myeloperoxidase (MPO) ANCA-positive. At diagnosis, the median age was 70 years [interquartile range (IQR) 64–78] and extra-renal manifestations were absent or subclinical (interstitial lung lesions in 10, 24%). The median (IQR) eGFR was 23 mL/min/1.73 m2 (15–35); six patients (15%) had started renal replacement therapy (RRT). All had proteinuria (median 1180 mg/24 h, IQR 670–2600) and micro-haematuria. Main histologic findings were extracapillary proliferation at chronic stages and glomerulosclerosis; following Berden’s classification, 6/28 biopsies (21%) were ‘focal’, 1/28 (4%) ‘crescentic’, 9/28 (32%) ‘mixed’ and 12/28 (43%) ‘sclerotic’. At last follow-up (median 32 months, IQR 12–52), 20/34 patients (59%) treated with immunosuppression had eGFR improvement >25% as compared with diagnosis, while 4/34 (12%) had started RRT.

Conclusions

AAV may present with slow renal disease progression; this subset is hallmarked by advanced age at diagnosis, positive MPO-ANCA, subclinical interstitial lung lesions and chronic damage at kidney biopsy. Partial renal recovery may occur following immunosuppression.
Metformin directly suppresses atherosclerosis in normoglycaemic mice via haematopoietic adenosine monophosphate-activated protein kinase
Authors: Seneviratne Anusha , Cave Luke , Hyde Gareth , Moestrup Soren Kragh , Carling David , Mason Justin C , Haskard Dorian O , Boyle Joseph James
Published: June 2020

Aims

Atherosclerotic vascular disease has an inflammatory pathogenesis. Heme from intraplaque haemorrhage may drive a protective and pro-resolving macrophage M2-like phenotype, Mhem, via AMPK and activating transcription factor 1 (ATF1). The antidiabetic drug metformin may also activate AMPK-dependent signalling. Hypothesis: Metformin systematically induces atheroprotective genes in macrophages via AMPK and ATF1, thereby suppresses atherogenesis.

Methods and results

Normoglycaemic Ldlr−/− hyperlipidaemic mice were treated with oral metformin, which profoundly suppressed atherosclerotic lesion development (P < 5 × 10−11). Bone marrow transplantation from AMPK-deficient mice demonstrated that metformin-related atheroprotection required haematopoietic AMPK [analysis of variance (ANOVA), P < 0.03]. Metformin at a clinically relevant concentration (10 μM) evoked AMPK-dependent and ATF1-dependent increases in Hmox1, Nr1h2 (Lxrb), Abca1, Apoe, Igf1, and Pdgf, increases in several M2-markers and decreases in Nos2, in murine bone marrow macrophages. Similar effects were seen in human blood-derived macrophages, in which metformin-induced protective genes and M2-like genes, suppressible by si-ATF1-mediated knockdown. Microarray analysis comparing metformin with heme in human macrophages indicated that the transcriptomic effects of metformin were related to those of heme, but not identical. Metformin-induced lesional macrophage expression of p-AMPK, p-ATF1, and downstream M2-like protective effects.

Conclusion

Metformin activates a conserved AMPK-ATF1-M2-like pathway in mouse and human macrophages, and results in highly suppressed atherogenesis in hyperlipidaemic mice via haematopoietic AMPK.
Surgical revascularization for acute coronary syndromes: a report from the North Rhine-Westphalia surgical myocardial infarction registry
Authors: Liakopoulos Oliver J , Slottosch Ingo , Wendt Daniel , Welp Hendryk , Schiller Wolfgang , Martens Sven , Choi Yeong-Hoon , Welz Armin , Pisarenko Julia , Neuhäuser Markus , Jakob Heinz , Ruhparwar Arjang , Wahlers Thorsten , Thielmann Matthias
Published: June 2020

OBJECTIVES

The aim of this was to analyse current outcomes in patients referred to coronary artery bypass grafting (CABG) for acute coronary syndromes (ACSs), including ST-elevation or non-ST-elevation ACS (non-ST-segment elevation myocardial infarction) or unstable angina.

METHODS

Patients (n = 2432) undergoing CABG for ACS between January 2010 and December 2017 were prospectively entered into a surgical myocardial infarction registry in North Rhine-Westphalia, Germany. Key end points were in-hospital all-cause mortality (IHM) and major adverse cardio-cerebral events (MACCE). Predictors for IHM and MACCE were analysed by multivariable logistic regression.

RESULTS

Patients (78% males) were referred for CABG for unstable angina (25%), non-ST-segment elevation myocardial infarction (50%), and ST-segment elevation myocardial infarction (25%). The mean patient age was 68 ± 11 years, logistic EuroSCORE was 19 ± 18% and three-vessel and left main stem diseases were diagnosed in 81% and 45% of patients, respectively. On-pump CABG with cardiac arrest or beating heart was performed in 92% and 2%, respectively, with only 6% off-pump surgery and 6% multiple arterial revascularization (3.1 ± 1.0 grafts, 93% left internal thoracic artery). Emergency CABG was performed in 23% of patients (42% in ST-segment elevation myocardial infarction; P < 0.001). The total IHM and MACCE rates were 8.1% and 17.5% and were highest in ST-segment elevation myocardial infarction patients with 12.6% and 28.5%, respectively (P < 0.001). Key predictors for IHM and MACCE were female gender, elevated troponin, left ventricular ejection fraction, inotropic support, logistic EuroSCORE, cardiopulmonary bypass and aortic clamp time and the need for emergency CABG.

CONCLUSIONS

Surgical myocardial revascularization in patients with ACS is still linked to substantial in-hospital mortality. Emergency CABG for patients with ACS was associated with poorer outcomes.
Letting the masses pay for the welfare state: tax regressivity in postwar Sweden
Authors: Lantz Gunnar
Published: June 2020

The mixed economy of the twentieth century shows conflicting developments in tax collection. Progressive taxes to limit top incomes are not the whole story. An examination of Sweden 1958–2012 shows that the progressivity of direct taxes was offset by consumption taxes and social security contributions. Previous studies conclude that tax progressivity peaked in the 1980s. This study shows instead how Swedish taxation became regressive in that period. The literature on welfare regimes and redistributive universalism relies empirically on conditions in the 1980s. Sweden did exhibit universalism in social spending but also a corresponding universalism in revenue collection.
Symmetric pressure stabilization for equal-order finite element approximations to the time-dependent Navier–Stokes equations
Authors: García-Archilla Bosco , John Volker , Novo Julia
Published: June 2020

Non-inf-sup-stable finite element approximations to the incompressible Navier–Stokes equations based on equal-order spaces for velocity and pressure are studied in this paper. To account for the violation of the discrete inf-sup condition, different types of symmetric pressure stabilization terms are considered. It is shown in the numerical analysis that these terms also improve stabilization of dominating convection in the following sense: error bounds with constants independent of inverse powers of the viscosity are derived. For proving the bound for the $L^2$ error of the pressure the choice of a suitable initial approximation for the velocity is essential.
Enhancing leniency programme in public markets
Authors: Alexia Giosa Penelope
Published: June 2020

The article focuses on the leniency programme, the key mechanism to strengthen the public enforcement of competition law, and its compatibility with the debarment mechanism and self-cleaning measures, which are both procurement remedies. As the article will show, procurement remedies interfere with cartel enforcement and the debarment mechanism undermines leniency in public procurement. The fact that firms may be banned from bidding, where there are plausible indications for their participation in agreements aiming at distorting competition, discourages infringing companies from coming forward and self-reporting. Even the self-cleaning measures under the current procurement Directive 2014/24/EU, which aim to help debarred firms to avoid exclusion or minimize its risk, undermine leniency in public procurement. This is particularly true after the recent judgment of the European Court of Justice in c-124/17 Vossloh Laeis GmbH v Stadtwerke München GmbH case. In this case, it was held that a contracting authority must be able to ask a leniency applicant to provide the decision of the competition authority concerning it. This must apply even if there is a pending private action for damages for breach of competition law by the contracting authority against that leniency applicant. In view of the above conflicting policy objectives, a number of proposals are discussed in order to better align leniency programmes with the mechanism of debarment and self-cleaning policy in public procurement. In this way, the article contributes to the optimal design of enforcement policies.
Quadruple advanced synchronous colorectal cancers successfully treated by laparoscopic surgery: a case report
Authors: Ma Jianwei , Akagi Tomonori , Etoh Tsuyoshi , Kono Yohei , Hiratsuka Takahiro , Suzuki Kosuke , Ninomiya Shigeo , Shibata Tomotaka , Ueda Yoshitake , Toujigamori Manabu , Shiroshita Hidefumi , Shiraishi Norio , Inomata Masafumi
Published: June 2020

Among synchronous colorectal cancers (SCRCs) reported previously, the incidence of quadruple advanced SCRCs is very rare. We present the case who underwent laparoscopic two-segment resection of the colon requiring two anastomoses that was performed for quadruple advanced cancers, and four tumors were curatively removed. There were no signs of recurrence at 64 months after surgery. Laparoscopic surgery provided less invasiveness even for quadruple advanced SCRCs in terms of early recovery with an acceptable long-term outcome.
Impact of Succinct Training on Open Cricothyrotomy Performance: A Randomized, Prospective, Observational Study of U.S. Army First Responders
Authors: Muller Kurtis L , Facciolla Cynthia A , Monti Jonathan , Cronin Aaron
Published: June 2020

Introduction

Primary airway failure has become the second most common cause of potentially survivable battlefield fatality. Cricothyrotomy is taught to all U.S. military providers as a means of securing an airway in extremis. However, retrospective studies show that cricothyrotomy failure rates for U.S. military first responders performing the procedure in combat is 33%. Our hypothesis was that these rates could be improved.

Materials and Methods

We conducted a randomized, prospective, observational study to evaluate the effects of inexpensive, succinct training on open cricothyrotomy performance by studying two unique U.S. Army First Responder participant groups. One participant group consisted of regular U.S. Army Medics (68 Ws). The second group was Special Operations Combat Medics. We evaluated both groups’ baseline ability to correctly perform a cricothyrotomy and then randomly assigned individuals within each group to either a training or practice group.

Results

The training group had a higher proportion of success and performed the cricothyrotomy faster than the practice group with 68 Ws group appearing to benefit most from training: their procedural success rates increased by an average of 23%, and their average time-to-correct-placement decreased by 21 seconds—a 33% improvement over baseline.

Conclusion

With one manikin, a qualified trainer, and $35 worth of expendable supplies, 10 medics could be trained in the procedure in just 2–3 hours. Our study suggests that this simple intervention has the potential to significantly improve U.S. Army First Responders’ ability to correctly perform an open cricothyrotomy and drastically decrease the time needed to perform this lifesaving procedure correctly, possibly saving one in four potentially survivable combat casualties suffering from airway compromise.
Improving the Efficiency of a Military Treatment Facility Transfer Center Process
Authors: Emry Marvin E , Settelmeyer Deanna R , McMann Leah P , Hopkinson Susan G
Published: June 2020

Introduction

A performance improvement project was initiated at Tripler Army Medical Center (TAMC) to decrease the amount of inpatient stays by military beneficiaries at civilian hospitals. Before the start of the project, the transfer process from external emergency rooms was completed by patient administration personnel and residents. This process had a median time to disposition decision of 40 minutes and led to missed opportunities for TAMC to care for military beneficiaries. The goals for the project were to have the median transfer process at less than 30 minutes from first call to time of disposition, to minimize unnecessary transfer denials, and to improve the perception of TAMC transfer process.

Materials and Methods

The team implemented multiple countermeasures as a performance improvement project to improve the transfer process. These included enhancing technological capabilities, providing clinically trained personnel to answer initial telephone calls, establishing rapid attending physician contact for acceptance, and standardizing data collection. Descriptive data were used to describe the progress toward project goals to include median time to disposition, number of monthly calls, and reasons for denials of patient transfers.

Results

The project met all proposed goals. The median time to disposition decision was reduced to 22 minutes. The primary reasons for denials included that the transfer was considered medically unnecessary (40.6%), no beds were available (18.9%), and the patient was unstable for transport (14.9%). As a reflection of improved customer service, there was an overall increase in transfer requests and positive feedback from the referring physicians at the local civilian hospitals.

Conclusion

The improved transfer process at TAMC resulted in a decreased median time of transfer request process, increased total transfer requests, and improved relationships with local civilian hospitals. While we acknowledge that each MTF has facility and regional characteristics (such as capability, capacity, military staffing, and degree of availability of civilian healthcare resources) that may contribute to variation from TAMC, the concepts and changes made in the transfer process may be considered a best practice to be adopted by other military facilities to promote the recapture of beneficiaries into the Defense Health Agency system.
Asymptomatic patients and asymptomatic phases of Coronavirus Disease 2019 (COVID-19): a population-based surveillance study
Authors: Zheng Xueying , Luo Sihui , Sun Yong , Han Mingfeng , Liu Jian , Sun Liangye , Zhang Liangming , Ling Ping , Ding Yu , Jin Tengchuan , Liu Zhirong , Weng Jianping
Published: June 2020

In this population-based study, we identified 307 confirmed COVID-19 cases from massive surveillance, including 129 551 individuals screened at fever clinics or returning from Hubei and 3710 close contacts of confirmed COVID-19 patients. Among them, 17 patients were asymptomatic at initial clinical assessment. These asymptomatic patients on admission accounted for a small proportion of all patients (5.54%) with relatively weak transmissibility, and the detection rate was 0.35 per 100 close contacts. Moreover, the dynamics of symptoms of the 307 patients showed that the interval from symptom remission to the final negativity of viral nucleic acid was 5.0 days (interquartile range 2.0 to 11.0 days), with 14 patients (4.56%) having re-detectable viral RNA after discharge. Overall, our findings suggested asymptomatic carriers and presymptomatic patients only accounted for a small proportion of COVID-19 patients. Also, the asymptomatic phase during recovery from COVID-19 implied that negativity in viral RNA is necessary as a de-isolation criterion and follow-up is recommended.
Numerical simulation of solar photospheric jet-like phenomena caused by magnetic reconnection
Authors: Kotani Yuji , Shibata Kazunari
Published: June 2020

Jet phenomena with a bright loop in their footpoint, called anemone jets, have been observed in the solar corona and chromosphere. These jets are formed as a consequence of magnetic reconnection, and from the scale universality of magnetohydrodynamics (MHD), it can be expected that anemone jets exist even in the solar photosphere. However, it is not necessarily apparent that jets can be generated as a result of magnetic reconnection in the photosphere, where the magnetic energy is not dominant. Furthermore, MHD waves generated from photospheric jets could contribute to chromospheric heating and spicule formation; however, this hypothesis has not yet been thoroughly investigated. In this study, we perform three-dimensional MHD simulation including gravity with the solar photospheric parameter to investigate anemone jets in the solar photosphere. In the simulation, jet-like structures were induced by magnetic reconnection in the solar photosphere. We determined that these jet-like structures were caused by slow shocks formed by the reconnection and were propagated approximately in the direction of the background magnetic field. We also suggested that MHD waves from the jet-like structures could influence local atmospheric heating and spicule formation.
Effect of Surgery for Stress Incontinence on Female Sexual Function
Authors: Glass Clark Stephanie M. , Huang Qi , Sima Adam P. , Siff Lauren N.
Published: June 2020

(Abstracted from Obstet Gynecol 2020;135:352–360)

A common problem in adult women is stress urinary incontinence (SUI), which affects about 1 in 3 women at some point in their lives. There is a direct relationship between female sexual dysfunction and severity of SUI.
Investigating the Association Between Post–Term Birth and Long Term Cognitive, Developmental and Educational Impacts: A Systematic Review and Meta-analysis
Authors: Williams Alessandra Glover , Odd David
Published: June 2020

(Abstracted from J Matern Fetal Neonatal Med 2020;33:1253–1265)

The impact of preterm birth on infant risk has been well established. However, the majority of the research on postterm birth, defined as 42 weeks and 0 days' gestational age and greater, has been focused on its association with immediate, short-term outcomes such as infection, stillbirth, and complications surrounding delivery.
Adding value in single-event multilevel surgery (SEMLS) for cerebral palsy patients with crouch gait: A retrospective study showing value added by a second surgeon
Authors: Baldwin Keith , Stevenson Kimberly L. , Spiegel David A. , Talwar Divya , Shah Apurva
Published: June 2020

Background:

Single event multilevel surgery (SEMLS) is a common treatment for ambulatory children with cerebral palsy (CP) who have bony and soft-tissue abnormalities at multiple levels within the lower extremities. We introduced a second surgical team to enable simultaneous bilateral procedures and assessed the cost savings resulting from simultaneous bilateral SEMLS versus staged bilateral SEMLS.

Methods:

We retrospectively reviewed patients with spastic diplegia treated by simultaneous or staged bilateral SEMLS from January 1, 2010, to December 1, 2015. We evaluated procedures performed, surgical duration, estimated blood loss (EBL) and blood transfusions, length of inpatient and rehabilitation admission, complications, and associated costs (normalized to 2015 dollars).

Results:

Eighteen eligible patients were identified with no significant differences in age, gender, or total number of procedures. Introduction of simultaneous bilateral SEMLS reduced costs by an average of $161,267. In this group, total length of stay was less for inpatient and rehabilitation stay. EBL was similar between the two groups: 683 mL versus 532 mL (P value 0.24). Thirty-six percent of the patients in the simultaneous group required a transfusion versus 0% in the staged group. Complications (n=3) in the staged group included infection, failure of fixation, and additional procedure for femoral derotation. Complications (n=2) in the simultaneous group included failure of fixation and readmission for symptomatic anemia.

Conclusions:

While some may favor staging interventions, simultaneous bilateral SEMLS with two surgical teams is a safe and effective alternative to help improve ambulatory function in CP patients associated with significant cost savings. The risk of allogenic blood transfusion may be increased with simultaneous bilateral SEMLS.

Level of Evidence:

Level IV.
Surgical and Nonoperative Management of Olecranon Fractures in the Elderly: A Systematic Review and Meta-Analysis
Authors: Chen Michael J. , Campbell Sean T. , Finlay Andrea K. , Duckworth Andrew D. , Bishop Julius A. , Gardner Michael J.
Published: June 2020

Objectives:

The aim of this comparative effectiveness study was to perform a meta-analysis of adverse events and outcomes in closed geriatric olecranon fractures, without elbow instability, after treatment with surgical or nonoperative management.

Data Sources:

PubMed, Web of Science, and Embase databases.

Study Selection:

Articles were included if they contained clinical data evaluating outcomes in patients ≥65 years of age with closed olecranon fractures, without elbow instability, treated surgically, or with nonoperative management.

Data Extraction:

Data regarding patient age, olecranon fracture type, fracture union, adverse events, reoperation, elbow range of motion, and surgeon and patient reported outcome measures were recorded according to intervention. The interventions included for analysis were tension band wire fixation, plate fixation, or nonoperative management.

Data Synthesis:

Separate random effects meta-analyses were conducted for each outcome according to intervention. Prevalence and 95% confidence intervals were calculated for dichotomous variables, whereas weighted means and confidence intervals were calculated for continuous variables.

Conclusions:

Comparable outcomes were achieved with surgical or nonoperative management of olecranon fractures in geriatric patients. Surgical intervention carried a high risk of reoperation regardless of whether plate or tension band wire fixation was used. Functional nonunion can be anticipated if nonoperative treatment is elected in low-demand elderly patients.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Cucurbitacin E inhibits esophageal carcinoma cell proliferation, migration, and invasion by suppressing Rac1 expression through PI3K/AKT/mTOR pathway
Authors: Zhang Luquan , Liang Hao , Xin Yanzhong
Published: June 2020

As an oxygenated tetracyclic triterpenoid, Cucurbitacin E (CuE) possesses potential antitumor properties in sorts of malignancies. However, its effect on human esophageal carcinoma cells has not been previously unearthed, and the mechanism underlying its anticarcinoma activity remains vague. Hence, this study was arranged to probe the function of CuE on esophageal carcinoma cells and its specific mechanism. Human esophageal carcinoma cells (ECA109 and EC9706) and human normal esophageal epithelial cells (Het-1A) were selected for subsequent experiments. The expression levels of Rac1 in esophageal carcinoma cells were measured. After transfection of sh-Rac1 or pCDNA3.1-Rac1, esophageal carcinoma cells were exposed to CuE. Then, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay and 5-ethynyl-2’-deoxyuridine staining were utilized for measurement of cell proliferation ability, cell scratch assay for inspection of cell migration rate, and Transwell for detection of cell invasion ability. The phosphorylation levels of protein kinase B and mTOR were analyzed by Western blot. Rac1 was highly expressed in esophageal carcinoma cells. Transfection of sh-Rac1 in esophageal carcinoma cells resulted in suppression on cell proliferation, migration, and invasion, as well as downregulated phosphorylation levels of AKT and mammalian target of rapamycin (mTOR) in esophageal carcinoma cells, while transfection of pCDNA3.1-Rac1 had an opposite effect, implicating that Rac1 can promote the viability of esophageal carcinoma cells. Esophageal carcinoma cells subjected to CuE treatment had decreased expression of Rac1, suppressed cell viability, and decreased phosphorylation levels of AKT and mTOR. Transfection of pCDNA3.1-Rac1 and CuE treatment in esophageal carcinoma cells enhanced viability of esophageal carcinoma cells and promoted the phosphorylation levels of AKT and mTOR in comparison with cells treated with CuE alone. CuE inhibits proliferation, invasion, and migration of esophageal carcinoma cells via downregulating Rac1 to block the phosphoinositide 3-kinase/AKT/mTOR pathway.
Alzheimer Gene BIN1 may Simultaneously Influence Dementia Risk and Androgen Deprivation Therapy Dosage in Prostate Cancer
Authors: Lehrer Steven , Rheinstein Peter H.
Published: June 2020

Background:

Androgen deprivation therapy (ADT) is extensively used in prostate cancer. Yet the risk of impaired cognition or Alzheimer disease (AD) in men with prostate cancer receiving ADT is uncertain. Some studies of prostate cancer and ADT suggest that the risk of AD is not increased. But other studies have found an increased risk of AD and cognitive impairment.

Objectives:

As the uncertainty about ADT and dementia might relate to the genetics of prostate cancer and AD, the authors used the Cancer Genome Atlas (TCGA) to examine the relationship in men with prostate cancer between genes implicated in AD and genes implicated in prostate cancer.

Methods:

The authors examined the genomics of 492 prostate cancer cases in the Genomic Data Commons (GDC) TCGA Prostate Cancer (PRAD) data set. To access and analyze the data, 2 web-based interfaces were used: (1) the UCSC Xena browser, a web-based visual integration and exploration tool for TCGA data, including clinical and phenotypic annotations; and (2) cBioportal, a web-based interface that enables integrative analysis of complex cancer genomics and clinical profiles.

Results:

Co-occurrence analysis indicates that alterations in the prostate cancer gene Speckle-type POZ protein (SPOP) significantly co-occur with alterations in the AD gene BIN1 (P<0.001). The presence of somatic mutations (deleterious and missense/in frame) in SPOP deranges BIN1 gene expression. SPOP/BIN1 RNA gene expression in 492 prostate cancer specimens is significantly correlated (P<0.001). Increased expression of SPOP in 492 prostate cancers is associated with reduced survival (P=0.00275). Men receiving pharmacologic therapy had a tumor with a significantly higher Gleason score (P=0.023). Gleason score and BIN1 RNA gene expression, unit log2 (fragments per kilobase of transcript per million mapped reads upper quartile [FPKM-UQ]+1), in 499 prostate cancer specimens were significantly inversely correlated (P<0.001).

Conclusions:

BIN1 forms part of a network that interacts with the MYC oncogene, activated at the earliest phases of prostate cancer and in its position on chr8q24 linked to disease aggressiveness. Dynamic regulation of the BIN1-Tau interaction is involved in AD. BIN1 loss in AD allows phosphorylated tau to be mis-sorted to synapses, which likely alters the integrity of the postsynapse, alongside reducing the functionally important release of physiological forms of tau. Alzheimer symptoms are usually preceded by a preclinical phase that may be 16 years long. The authors suggest that the ADT dosage reflects the severity of a process that is already underway. The severity is determined by the genetics of the tumor itself, at least in part by BIN1. ADT is not causing new cases of AD. The oncologist treats higher-grade prostate cancer with more ADT, which serves as a surrogate marker for disease severity. Our analysis of TCGA data does not support the idea that ADT causes AD or dementia.
Rosai–Dorfman Disease–Like Reaction to Tattoo
Authors: Naqvi Jaree , Cassarino David S.
Published: June 2020

A 47-year-old white man presented with a 14-month history of an asymptomatic 2-cm, slow-growing nodular lesion on his left shin that arose in the background of a black tattoo. An excisional biopsy followed by histological examination revealed a prominent lymphohistiocytic infiltrate, with many large, foamy histiocytic cells containing intact inflammatory cells within their cytoplasm, findings consistent with emperipolesis, a feature typical of Rosai–Dorfman disease (RDD). By immunohistochemistry, S-100 (a marker that is positive in almost all cases of RDD) was negative, arguing against the diagnosis of RDD. In addition, prominent black tattoo pigment was seen in many areas, expanding the differential diagnosis to include an unusual reactive lymphohistiocytic response to the tattoo mimicking RDD. Histologically, RDD shows many plasma cells, neutrophils, lymphocytes, and histiocytes with abundant foamy cytoplasm that contains intact lymphocytes and other cells, a phenomenon described as emperipolesis. A wide variety of cutaneous reactions to tattoos have been described, including tenderness, burning pain, inflammation, and pruritus. However, histologic features suggestive of RDD as a reaction to tattoo pigment have not been previously described and should therefore also be considered as a potential rare reaction pattern to tattoos.
Metastatic Prostatic Adenocarcinoma in Patient With Muir–Torre Syndrome Misdiagnosed as Metastatic Sebaceous Carcinoma: Case Report and Systematic Literature Review
Authors: Cattelan Leila , Abi-Rafeh Jad , Brimo Fadi , Kazan Roy , Redpath Margaret , Chergui May
Published: June 2020

Muir–Torre syndrome (MTS) is a rare autosomal dominant condition characterized by the presence of at least one cutaneous sebaceous tumor and one visceral malignancy, arising mostly from the gastrointestinal tract. We present the case of a 63-year-old man with several cutaneous and visceral neoplasias in the context of MTS, and a pelvic lymph node lesion diagnosed initially as metastatic sebaceous carcinoma, but later identified as metastasis from a newly diagnosed prostatic adenocarcinoma. Histological similarities between these 2 lesions are discussed. A systematic literature review was conducted evaluating all published cases of patients with MTS in which metastases were reported. Eighteen articles were included in the final synthesis, representing 20 patients with a total of 26 metastases. Seventeen patients (85%) exhibited metastases originating from MTS-related neoplasms, whereas only 2 patients (11%) exhibited metastases from concomitant malignancies. Of the 85% of patients with metastases from MTS-related malignancies, most originated from noncutaneous sources (78% from visceral neoplasms and 22% from sebaceous carcinomas). When stratifying according to metastases, 23 cases (88%) originated from MTS-related lesions, whereas only 3 (12%) originated from unrelated malignancies. Our findings thus demonstrate that most metastases found in MTS patients (88%) do indeed originate from MTS-related neoplasms. Nevertheless, it remains imperative that a broad differential diagnosis is maintained when assessing a novel lesion, to avoid misdiagnoses, as in the present case, with significant therapeutic and prognostic implications.
Apocrine Chromhidrosis
Authors: Shah Aadarsh , Tsianou Zoi , Suchak Ravi , Mann Jack
Published: June 2020

Apocrine chromhidrosis is a rare diagnosis that occurs due to colored sweat being secreted from the apocrine glands, which are located in the axillae, anogenital skin, and areolae and over the skin of the trunk, face, and scalp. We present the case of a 65-year-old woman who presented with a sudden onset of pink sweating affecting mainly her axillae but also her pelvis, causing staining of clothing and bed sheets. There was nil to note on examination and histology with immunostaining demonstrated focally prominent yellow-brown lipofuscin granules in the cytoplasm of the apocrine secretory cells confirming the diagnosis. The disease can have a significant psychosocial impact, and treatment remains challenging. Our case is unique because the red and pink coloring of sweat is less common in cases of apocrine chromhidrosis, which is often in favor of darker colored sweat, and the distribution involved the inguinal canal, which is also less often seen.
Effects of Dual Purinoceptor-dependent Approach on Release of Vascular Endothelial Growth Factor From Human Microvascular Endothelial Cell (HMEC-1) and Endothelial Cell Condition
Authors: Gdula Anna M. , Swiatkowska Maria
Published: June 2020

In the recent years, the awareness of the role purinergic signaling plays as a therapeutic target has increased considerably. The purinoceptor allows the action of extracellular nucleotides (P2 receptors) and intermediary products of their metabolism, such as adenosine (P1 receptors), regulating pivotal processes occurring in the cardiovascular system. This study focuses on a dual purinoreceptor-dependent approach, based on the activation of adenosine P1 receptors with the simultaneous inhibition of P2Y12 receptors that can be used as novel platelet inhibitors in antithrombotic therapy. Endothelial cells are directly exposed to the drugs circulating in the bloodstream. That is why effects of our concept on human microvascular endothelial cells (HMEC-1) were examined in in vitro studies, such as enzyme-linked immunosorbent assay and scratch assays. In response to adenosine receptor agonists, levels of secreted vascular endothelial growth factor varied. Two of them, 5′-N-ethylcarboxamidoadenosine and MRE0094 remarkably increased vascular endothelial growth factor release. The elevated levels were reduced when used together with the P2Y12 receptor antagonist. Also, rates of wound closure in a scratch assay were significantly reduced in these cases. The results suggest that the proposed treatment does not impair endothelial cell condition. In addition, it is suggested as a collateral benefit, namely solving the problem of excessive activation of endothelial cells during antiplatelet therapy.
BILATERAL EPIRETINAL MEMBRANE FORMATION AFTER INTRAVITREAL INJECTIONS OF AUTOLOGOUS MESENCHYMAL STEM CELLS
Authors: Kasetty Megan A. , Hedges Thomas R. , Witkin Andre J.
Published: June 2020

Purpose:

The authors describe a case of new bilateral epiretinal membranes and vitreous cells after intravitreal and sub-Tenon's injections of bone marrow–derived stem cells.

Methods:

A case report of a 43-year-old man with OPA-1 autosomal dominant optic atrophy who self-enrolled in a stem cell therapy clinical trial and received simultaneous bilateral intravitreal and sub-Tenon's injections of bone marrow–derived stem cells.

Results:

Within one month of receiving the injections, the patient developed epiretinal membranes and vitreous cells in both eyes, seen with optical coherence tomography.

Conclusion:

Stem cell therapy has been gaining popularity as a potential intervention for progressive retinal and optic nerve diseases; however, the mechanism of action of bone marrow–derived stem cells is still not well understood and may result in unintended cell differentiation.
Keratitis Caused by Candida parapsilosis and Subsequent Corynebacterium macginleyi Infection: Case Report and Short Review
Authors: Fejes Imre , Garcia-Hermosa Pedro , Bodin Anne
Published: June 2020

Keratitis due to Candida parapsilosis or Corynebacterium macginleyi is uncommon. We present a patient with several risk factors who suffered two subsequent corneal infections caused by these pathogens and healed with topical conservative therapy. The important factor was the early detection of infection. Fluconazole solution administered topically as eye drops combined with regular debridement proved in this case a successful alternative to systemic antifungal treatment. With a perceived recurrence of the keratitis, one must take into account the involvement of other pathogens present. The previous use of an antifungal solution other than a conventional eye drop could be an additional risk factor for a second bacterial infection, but the benefits should still rule in favor of such a treatment.
Adherence of Health Care Workers to Personal Protective Equipment During Coronavirus Disease 2019 Pandemic
Authors: Alabbood Majid
Published: June 2020

Background

An outbreak of a novel corona viral pneumonia started in China late 2019. World Health organization on March 11 declared coronavirus disease 2019 (COVID-19) a pandemic. In China, an estimated 3000 health care workers (HCWs) have been infected. The Centers for Disease Control and Prevention released recommendations for the use of personal protective equipment when treating patients with COVID-19 to minimize the risk of acquiring infection among HCWs. This study aimed to assess adherence of HCWs in Iraq to personal protective equipment during COVID-19 pandemic.

Methods

This was an online survey of a group of Iraqi doctors regarding their adherence to personal protective equipment.

Results

Most of the surveyed physicians (120) adequately follow the recommendations regarding their personal hygiene, use of masks/respirators, and wearing equipment while providing care for suspected or confirmed cases of COVID-19. However, 11% and 16% do not follow the recommendations while caring for COVID-19 cases and performing aerosol-generating procedures, respectively. Majority of the respondents admit the importance of these measures in lowering the risk of infection. Approximately, two third of the participants started the measures at the beginning or the middle of the outbreak.

Conclusions

Most of Iraqi heath care workers involved in the survey follow the recommendations regarding personal protective equipment.
Tocilizumab Utilization for Coronavirus Disease 2019
Authors: Gavioli Elizabeth M. , Sikorska Gabriela , Man Ammy , Rana Jay , Cusumano Jaclyn A.
Published: June 2020

Background

The deterioration of patients with coronavirus disease 2019 (COVID-19) has been hypothesized to be due to cytokine release syndrome including interleukin-6 (IL-6). Tocilizumab (TCZ) is an IL-6 inhibitor that may be a potential therapy for COVID-19.

Methods

Patients hospitalized for COVID-19 and treated with TCZ between March 1, 2020, and March 26, 2020, at an academic medical center in New York City were described. Patients were categorized as severe illness or critical illness based on previously described definitions. Outcomes assessed included respiratory status improvement, laboratory values, discharge, or death.

Results

A total of 12 patients were included in this case series. Ten patients were classified as critical and 2 as severe. Eight (n = 6 critical and n = 2 severe) patients had improvements in respiratory symptoms after receiving TCZ and were discharged, but 4 patients expired despite receiving therapy. All patients had an elevation in IL-6 and C-reactive protein levels before TCZ treatment. After TCZ treatment, there was a significant decrease in C-reactive protein levels (P = 0.002) and an increase in aspartate aminotransferase (P = 0.18) and alanine aminotransferase (P = 0.006) levels. Patients who received TCZ treatment later in their hospitalization course had a poor outcome.

Conclusions

Tocilizumab may play a role in treating patients with COVID-19 with elevated IL-6 levels, who are classified as severely ill and treated early in their disease course. The risks of adverse events and economic burdens should also be evaluated.
In vitro optical quality assessment of a monofocal IOL sutured to an artificial iris
Authors: Mayer Christian , Son Hyeck-Soo , Łabuz Grzegorz , Yildirim Timur M. , Auffarth Gerd U. , Khoramnia Ramin
Published: June 2020

Purpose:

To assess whether the combined implantation of a monofocal IOL and an artificial iris had an effect on the IOL's optical performance.

Setting:

David J. Apple International Laboratory for Ocular Pathology, Heidelberg, Germany.

Design:

In vitro laboratory study.

Methods:

IOL optical quality was assessed using an OptiSpheric IOL Pro II to measure the IOL's modulation transfer function (MTF) at 3.0 mm pupil size and spatial frequency of 100 lp/mm. Three ASPIRA-aAY IOLs with different base powers, 10.0 diopter (D) (IOL A), 20.0 D (IOL B), and 30.0 D (IOL C) were measured before and after suturing the IOL to an ArtificialIris (AI). The degree of IOL decentration about the center of the AI was also evaluated.

Results:

The mean MTF values prior to suturing were 0.57, 0.65, and 0.63 for IOLs A, B, and C, respectively. After suturing to the AI, the mean MTF values were 0.52, 0.54, and 0.55 for IOLs A, B, and C, respectively. The decentration values in vertical direction were 0.20 mm, 0.00 mm, and 0.02 mm for IOLs A, B, and C, respectively. In horizontal direction, the decentration values were 0.42 mm, 0.10 mm, and 0.03 mm for IOLs A, B, and C, respectively.

Conclusions:

The MTF decreased slightly in all 3 IOLs after they were sutured to the AI. The small differences, however, should be clinically irrelevant. This laboratory assessment showed that suturing of the IOL to the AI can be performed in a reliable and reproducible manner without deteriorating optical quality.
Oxygen Consumption and Speed Performance of a Runner with Amputation Wearing an Elevated Vacuum Running Prosthesis
Authors: Le Hoan , Guerra Gary , Sasaki Kazuhiko , Phongphibool Sitha , Smith John D. , Wongpanya Jirayu , Rakbanboong Thanyaporn , Siriwatsopon Juthamas
Published: June 2020

Introduction

Persons with lower-limb differences are increasingly seeking out a means to participate in sport and running activities. Suspension of the running-specific prosthesis (RSP) during high-intensity running is crucial for safety and optimal running performance. The vacuum-assisted socket system (VASS) provides enhanced proprioception and residual limb volume stability during walking; however, utilization of the VASS in an individual fit with an RSP has yet to be explored in case or empirical studies. We report outcomes of a recreational running transtibial prosthesis user wearing a novel VASS-RSP.

Methods

A 33-year-old man with transtibial amputation was provided an RSP with a VASS and performed outcome measures while wearing the VASS-RSP and non–VASS-RSP. He performed a series of straight and counterclockwise (CCW) curve track 40-m runs while speed gates recorded split and total time. The patient also performed a 10-minute treadmill run oxygen consumption was determined, and Socket Comfort Scores (SCS) were recorded.

Results

No significant differences in track running trials were observed; straight track running speeds were similar VASS (5.37 ± 0.06 m/s) and non–VASS-RSP (5.37 ± 0.16 m/s), [t(1) = 0.320, P = 0.979]. Curve track speeds improved while wearing the VASSRSP (4.72 ± 0.09 m/s) compared with the non–VASS-RSP (4.66 ± 0.03 m/s) [t(2) = 0.846, P = 0.487]. Speeds were significantly faster during straight track running (5.37 ± 0.08 m/s) than during curve track running (4.70 ± 0.07 m/s) when both RSP configurations were combined [t(4) = 15.8, P = 0.001]. Net oxygen consumption reduced while wearing VASS-RSP (24.6 mL/kg per minute) compared with non–VASS-RSP (29.2 mL/kg per minute). Socket comfort during outcome measures improved 33% while wearing the VASS-RSP.

Conclusions

The patient preferred using the VASS-RSP while performing running exercises, and some outcome measures comparing the two suction suspension systems support the patient values. The novel VASS system should be further tested to determine potential utility for running exercise and sport interventions for persons with amputation.