bluuebunny/crossref_metadata_2025 huggingface dataset:
Ambulatory blood pressure adaptations to high-intensity interval training: a randomized controlled study
Authors: Edwards Jamie J. , Taylor Katrina A. , Cottam Christian , Jalaludeen Navazh , Coleman Damian A. , Wiles Jonathan D. , Sharma Rajan , O’Driscoll Jamie M.
Published: October 2020

Objective:

Hypertension remains the leading cause of cardiovascular disease and premature mortality globally. Although high-intensity interval training (HIIT) is an effective nonpharmacological intervention for the reduction of clinic blood pressure (BP), very little research exists regarding its effects on ambulatory BP. The aim of this study was to measure alterations in ambulatory and clinic BP following HIIT in physically inactive adults.

Methods:

Forty-one participants (22.8 ± 2.7 years) were randomly assigned to a 4-week HIIT intervention or control group. The HIIT protocol was performed on a cycle ergometer set against a resistance of 7.5% bodyweight and consisted of 3 × 30-s maximal sprints separated with 2-min active recovery. Clinic and ambulatory BP was recorded pre and post the control period and HIIT intervention.

Results:

Following the HIIT intervention, 24-h ambulatory BP significantly decreased by 5.1 mmHg in sBP and 2.3 mmHg in dBP (P = 0.011 and 0.012, respectively), compared with the control group. In addition, clinic sBP significantly decreased by 6.6 mmHg compared with the control group (P = 0.021), with no significant changes in dBP and mean BP (mBP). Finally, 24-h ambulatory diastolic, daytime sBP, mBP and dBP, and night-time sBP and mBP variability significantly decreased post-HIIT compared with the control group.

Conclusion:

HIIT remains an effective intervention for the management of BP. Our findings support enduring BP reduction and improved BP variability, which are important independent risk factors for cardiovascular disease.
Does higher SBP at discharge explain better outcomes in non-heart failure with reduced ejection fraction patients? Insights from Fuwai Hospital
Authors: Yao Younan , Zhang Rongcheng , Zhang Qi , Zhao Xinke , Zhang Jian
Published: October 2020

Objective:

We hypothesized that discharge SBP had different associations with outcomes in non-HFrEF (left ventricular ejection fraction ≥40%) patients with or without high blood pressure (HBP) at admission.

Methods:

Non-HFrEF patients hospitalized for decompensated heart failure were consecutively recruited and were categorized into HBP (admission SBP ≥130 mmHg) group and non-HBP group. The primary outcome was a composite of cardiovascular death and heart transplantation. Multivariate Cox and penalized spline analyses were used to assess the relationships between discharge SBP and outcomes.

Results:

Nine hundred and sixty-four non-HFrEF patients were enrolled with a median follow-up of 71.8 months. Three hundred and sixty-five (37.9%) patients had HBP. In multivariate Cox analyses, non-HBP patients with higher discharge SBP were associated with a better outcome (per 10 mmHg increased, hazard ratio = 0.788, P = 0.001). However, an opposite relationship between discharge SBP and the primary outcome was observed in HBP group (per 10 mmHg increased, hazard ratio = 1.312, P = 0.002). Results of penalized spline regression models showed that there was a U-shaped association between discharge SBP and outcomes in the total cohort. Compared with 120 mmHg, the risk of the primary outcome increased when discharge SBP was below 99 mmHg in non-HBP group; in HBP group, a worse outcome was observed when discharged SBP was above 145 mmHg.

Conclusion:

Non-HFrEF had a U-shaped association between discharge SBP and adverse events. Such an association was modified by admission HBP. Higher discharge SBP correlated with a worse outcome in non-HFrEF patients with admission HBP, as opposed to patients admitted without HBP.
Comparative effects of intensive-blood pressure versus standard-blood pressure-lowering treatment in patients with severe ischemic stroke in the ENCHANTED trial
Authors: Minhas Jatinder S. , Wang Xia , Lindley Richard I. , Delcourt Candice , Song Lili , Woodward Mark , Lee Tsong-Hai , Broderick Joseph P. , Pontes-Neto Octavio M. , Kim Jong S. , Ricci Stefano , Lavados Pablo M. , Bath Philip M. , Durham Alice C. , Wang Ji-Guang , Sharma Vijay K. , Demchuk Andrew M. , Martins Sheila O. , Chalmers John , Anderson Craig S. , Robinson Thompson G.
Published: October 2020

Objective:

Limited data exist on the optimum level of SBP in thrombolyzed patients with acute ischemic stroke (AIS). We aimed to determine the effects of intensive blood pressure (BP) lowering, specifically in patients with severe AIS who participated in the international, Enhanced Control of Hypertension and Thrombolysis Stroke Study.

Methods:

Prespecificed subgroup analyzes of the BP arm of Enhanced Control of Hypertension and Thrombolysis Stroke Study, a multicenter, partial–factorial, open, blinded outcome assessed trial, in which 2227 thrombolysis-eligible and treated AIS patients with elevated SBP (>150 mmHg) were randomized to intensive (target 130–140 mmHg) or guideline-recommended (<180 mmHg) BP management. Severe stroke was defined by computed tomography or magnetic resonance angiogram confirmation of large-vessel occlusion, receipt of endovascular therapy, final diagnosis of large artery atheromatous disease, or high (>10) baseline neurological scores on the National Institutes of Health Stroke Scale. The primary efficacy outcome was death or any disability (modified Rankin scale scores 2–6). The key safety outcome was intracranial hemorrhage (ICH). Treatment effects estimated in logistic regression models are reported as odds ratios (ORs) with 95% confidence intervals (CIs).

Results:

There were 1311 patients [mean age 67 years; 37% female; median baseline National Institutes of Health Stroke Scale of 11 (range 6.0–15.0)] with severe AIS. Overall, there was no significant difference in the primary outcome of death or disability. However, intensive BP lowering significantly increased mortality (OR 1.52, 95% CI 1.09–2.13; P = 0.014) compared with guideline BP lowering, despite significantly lowering clinician-reported ICH (OR 0.63, 95% CI 0.43–0.92; P = 0.016).

Conclusion:

Intensive BP lowering is associated with increased mortality in patients with severe AIS despite lowering the risk of ICH. Further randomized trials are required to provide reliable evidence over the optimum SBP target in the most serious type of AIS.

Trial registration:

ClinicalTrials.gov Identifier: NCT01422616.
Sympathetic nerve traffic overactivity in chronic kidney disease: a systematic review and meta-analysis
Authors: Grassi Guido , Biffi Annalisa , Seravalle Gino , Bertoli Silvio , Airoldi Flavio , Corrao Giovanni , Pisano Anna , Mallamaci Francesca , Mancia Giuseppe , Zoccali Carmine
Published: October 2020

Background:

Studies based on microneurographic sympathetic nerve activity (MSNA) recordings have shown that the sympathetic system is overactivated in chronic kidney disease (CKD) patients but the relationship between MSNA and renal function and other risk factors has not been systematically reviewed in this population.

Design and measurements:

This meta-analysis compares MSNA in cardiovascular complications-free CKD patients (n = 638) and healthy individuals (n = 372) and assesses the relationship of MSNA with the eGFR, age, BMI and hemodynamic variables.

Results:

In a global analysis, MSNA was higher in CKD patients than in healthy control individuals (P < 0.001). The difference in MSNA between patients and healthy individuals was more marked in end-stage kidney diseases patients than in stage 3A 3B CKD patients (P < 0.001). In an analysis combining patients and healthy individuals, MSNA rose gradually across progressively lower eGFR categories (P < 0.01). In separate meta-regression analyses in CKD patients and in healthy individuals, MSNA associated directly with age (CKD: r = 0.57, P = 0.022; healthy individuals: r = 0.71, P = 0.031) and with the BMI (r = 0.75, P = 0.001 and r = 0.93, P = 0.003). In both groups, MSNA correlated with heart rate (r = 0.77, P = 0.02 and r = 0.66, P = 0.01) but was unrelated to plasma norepinephrine.

Conclusion:

Independently of comorbidities, MSNA is markedly increased in CKD patients as compared with healthy individuals and it is related to renal function, age, the BMI and heart rate. Sympathetic activation intensifies as CKD progresses toward kidney failure and such an intensification is paralleled by a progressive rise in heart rate but it is not reflected by plasma norepinephrine.
Ocular Sequelae of Stevens–Johnson Syndrome: A Comprehensive Approach
Authors: Iyer Geetha , Srinivasan Bhaskar , Agarwal Shweta
Published: October 2020

The chronic sequelae of Stevens–Johnson syndrome cause severe ocular morbidity. Among the various manifestations, including dry eye, cicatrization causing forniceal shortening, adnexal disorders, lid margin keratinization, and limbal stem cell deficiency, keratinization of the lid margin leads to progressive ocular surface damage through constant blink-induced microtrauma. This damage induces corneal punctate keratopathy and neovascularization and can produce epithelial defects leading to corneal infection or perforation. Management strategies for chronic ocular sequelae are broadly categorized into ocular surface stabilization procedures, tectonic procedures, and visual rehabilitation procedures. Interventions in the acute stage of the disease include amniotic membrane grafting. Timely intervention helps to prevent deterioration of the ocular surface in these eyes.
Histologic Findings of Trabecular Meshwork and Schlemm’s Canal After Microhook Ab Interno Trabeculotomy
Authors: Tsutsui Aika , Hamanaka Teruhiko , Manabe Kaoru , Kaidzu Sachiko , Kumasaka Toshio , Tanito Masaki
Published: October 2020

Introduction:

Trabeculotomy (LOT) and related goniotomy surgeries are classified based on excision or incision of the trabecular meshwork (TM); however, histologic evidence of the incision/excision pattern is insufficient.

Case Presentations:

Two cases of glaucomatous eyes in which trabeculectomy specimens previously “incised” during LOT were assessed histologically. A 39-year-old man with juvenile open-angle glaucoma (case 1) and a 70-year-old man with exfoliation glaucoma (case 2) underwent trabeculectomy for insufficient intraocular pressure reduction or visual field progression after initial microhook ab interno trabeculotomy (μLOT). In case 1, Schlemm’s canal (SC) opened into the anterior chamber due to extensive absence of the inner wall of SC and TM. In case 2, SC endothelium (SCE)-marker CD34 staining showed the slit-like entry site of a previous LOT, the SC lumen was sealed partially by scleral tissue, and CD34-positive and CD34-negative areas in the SC wall suggested SCE dropout and partial conversion of SC into ghost vessels. Active aqueous outflow-marker podoplanin (D2-40) staining showed intense immunolabeling in the sclera between the entry site and collector channels, indicating aqueous outflow.

Discussion:

The μLOT cleft can appear as both incisional and excisional patterns. In addition to incremental conventional outflow with reduced TM resistance, another unconventional outflow may be a mechanism of IOP reduction after LOT procedures.
Effect of Toric Intraocular Lens Implantation on Visual Acuity and Astigmatism Status in Eyes Treated With Microhook Ab Interno Trabeculotomy
Authors: Ichioka Sho , Manabe Kaoru , Tsutsui Aika , Takai Yasuyuki , Tanito Masaki
Published: October 2020

Précis:

Use of toric intraocular lenses is a reasonable option for better visual outcomes when a combined minimally invasive glaucoma surgery (MIGS) and cataract surgery is performed in eyes with corneal astigmatism.

Purpose:

To assess the efficacy of toric intraocular lenses (IOLs) in combined cataract and MIGS, visual and refractive outcomes were compared between eyes implanted with nontoric and toric IOLs during microhook ab interno trabeculotomy triple procedures.

Methods:

Glaucomatous eyes with preexisting corneal astigmatism exceeding −1.5 D implanted with nontoric (n=10) or toric (n=10) IOLs were evaluated retrospectively. The uncorrected visual acuity (UCVA) and refractive astigmatism preoperatively and 3 months postoperatively were compared.

Results:

Preoperatively, the groups had similar logarithm of the minimum angle of resolution (logMAR) UCVAs and refractive astigmatism. Postoperatively, the logMAR UCVA (toric, 0.07±0.07; nontoric, 0.33±0.30; P=0.0020) was significantly better and the refractive astigmatism (toric, −0.63±0.56 D; nontoric, −1.53±0.74 D; P=0.0110) significantly less in the toric group. The toric group had postoperative improvements in the logMAR UCVA (−0.58, P=0.0039) and refractive astigmatism (+1.45 D, P=0.0195). Vector analyses showed the postoperative centroid magnitude of refractive astigmatism was less in the toric group (0.23 D at 83 degrees) than the nontoric group (1.03 D at 178 degrees). Postoperatively, 70% of eyes in the toric group had 1.0 D or less refractive astigmatism compared with 10% in the nontoric group. Surgically induced astigmatism (nontoric group, 0.62 D at 10 degrees; toric group, 0.50 D at 113 degrees) and intraocular pressure reduction (22% in both groups) did not differ between groups.

Conclusions:

Better visual outcomes may be achieved with toric IOLs when a combined MIGS/cataract surgery is performed in eyes with corneal astigmatism.
Novel CUBN Mutation in a Young Child With Megaloblastic Anemia
Authors: Falcon Corey , Hamm Austin J. , Li Geling , Lebensburger Jeffrey , Howard Thomas H. , Xavier Ana C.
Published: October 2020

Inherited disorders of cobalamin (Cbl, vitamin B12) metabolism are rare causes of megaloblastic anemia and neurologic abnormalities. More prevalent in certain ethnic groups, these disorders occur despite adequate Cbl intake and usually result from abnormal vitamin cell transport or processing. Cubilin (CUBN, intrinsic factor-cobalamin receptor) is the intestinal receptor for the endocytosis of intrinsic factor—vitamin B12. Its gene is localized to chromosome 10p13 and mutations involving CUBN have been described in patients with congenital megaloblastic anemia. In this report, we describe a novel CUBN pathogenic variant in a child with megaloblastic anemia.
Extramedullary Hematopoiesis in the Dura Mater During Treatment of a CNS Embryonal Tumor
Authors: Ganapathi Shireen S. , Havard Molly E. , Ferguson Mark , Cole Bonnie L. , Millard Nathan E. , Vitanza Nicholas A.
Published: October 2020

Extramedullary hematopoiesis (EMH) is hematopoiesis occurring outside of the bone marrow. It has been reported to develop in abdominal organs or lymph nodes after chemotherapy. Here, the authors describe a patient with a localized central nervous system embryonal tumor who, during intensive chemotherapy, developed dural nodules. Biopsy revealed these nodules to be EMH. Without a pathologic diagnosis, this may have been considered disease progression, altering the patient’s treatment plan. This report intends to serve as a reminder that EMH should be included in the differential diagnosis of suspicious lesions and highlights the importance of their biopsy because of potential management implications.
Cyanosis Due to Methemoglobinemia as the Presenting Sign of Glucose-6-Phosphate Dehydrogenase Deficiency in a Child: Diagnostic and Clinical Implications
Authors: Pomoni Angeliki , Aggeli Ioanna , Loutsi Eleni , Hatzimichael Eleftheria , Chaliasos Nikolaos , Makis Alexandros
Published: October 2020

A previously healthy 3-year-old boy presented with pallor, jaundice, cyanosis, and a 24-hour history of vomiting and anorexia following fava bean ingestion. Clinical examination and laboratory findings were consistent with severe nonimmune hemolytic anemia with methemoglobinemia. Given the patient’s history, a previously unrecognized glucose-6-phosphate dehydrogenase deficiency was suspected and diagnosed. The aim of this article is to delineate the possible coexistence of methemoglobinemia and glucose-6-phosphate dehydrogenase deficiency in children presented with acute hemolysis and discuss its management while reviewing the existing literature.
Xylazine, a Veterinary Tranquilizer, Detected in 42 Accidental Fentanyl Intoxication Deaths
Authors: Nunez Jacqueline , DeJoseph Maura E. , Gill James R.
Published: October 2020

Xylazine is an emerging adulterant with fentanyl in fatal drug intoxications, which has public health, safety, and criminal investigative implications. Xylazine is a nonnarcotic sedative used for analgesia and muscle relaxation exclusively in veterinary medicine. Its chemical structure is similar to clonidine and acts as a central α-2 agonist which may cause bradycardia and transient hypertension followed by hypotension. We report the detection of xylazine in 42 deaths in Connecticut from March to August 2019. Xylazine combined with an opioid or stimulant may affect the toxicity of these drugs. Detection of xylazine may help the forensic pathologist distinguish illicit from prescribed fentanyl, and law enforcement agents track the illicit drugs to a specific drug supplier. Because of its lack of response to naloxone, emergency medicine physicians need to be aware of its potential presence as it may affect therapy.
18F-Fluciclovine–Avid Mediastinal Lymph Node Metastasis of Cutaneous Malignant Melanoma
Authors: Shariftabrizi Ahmad , Pillenahalli Maheshwarappa Ravishankar , Kahn Daniel , Pollard Janet
Published: October 2020

A 63-year-old man with recent diagnosis of high-risk prostate adenocarcinoma was referred to our Nuclear Medicine Department for 18F-fluciclovine PET/CT to rule out metastasis in the setting of elevated serum prostate-specific antigen levels. The patient had previous history of nodular melanoma of the right cheek treated 6 years back with surgery and adjuvant radiation. Surveillance 18F-FDG PET/CT for melanoma 1 month back had revealed enlarged FDG-avid mediastinal para-aortic lymph nodes, which on endoscopic biopsy had revealed melanoma metastasis. On current fluciclovine PET/CT, the same enlarged para-aortic lymph nodes showed fluciclovine uptake, suggesting false-positive uptake.
An Unusual Case of Maxillary Sinus Cholesterol Granuloma Showing FDG Uptake on PET/CT
Authors: Umeda Naoki , Hayama Masaki , Nakamura Akiko , Maeda Yohei , Inohara Hidenori
Published: October 2020

Cholesterol granuloma (CG) occurs primarily in the middle ear and rarely in the paranasal sinus. We report an unusual case of paranasal sinus CG with 18F-FDG uptake. A 76-year-old man presented with right refractory epistaxis. PET/CT showed FDG uptake in the maxillary sinus. CT findings are typically uncharacteristic, whereas MRI scans are characterized by a high signal on both T1-weighted and T2-weighted images. Nasal endoscopy from the ostium revealed a granulomatous lesion with hemorrhage at the base of the maxillary sinus. After pathological examination by endoscopic sinus surgery, the patient was diagnosed with CG.
Clinicopathologic Characteristics of Late Acute Antibody-mediated Rejection in Pediatric Liver Transplantation
Authors: Zhou Shengmei , Mitsinikos Tania , Emamaullee Juliet , Weaver Carly , Wang Larry , Shillingford Nick , Warren Mikako , Bawab Julie Huss , Tiwari Nishant , Genyk Yuri , Thomas Danny , Parham David M.
Published: October 2020

Background.

An early and accurate diagnosis of liver antibody-mediated rejection (AMR) followed by timely intervention is important for clinical management but remains challenging. The aim of this study was to assess the clinicopathologic characteristics and outcomes of late acute AMR in pediatric liver transplantation recipients.

Methods.

We performed a retrospective review of 739 ABO-identical/compatible allograft liver biopsies from 199 pediatric transplantation recipients.

Results.

Based on Banff 2016 AMR criteria, 3 recipients fulfilled the criteria for definite for late acute AMR, 2 met the criteria for suspicious for AMR, and 2 were indeterminate for AMR. We further assessed the clinicopathologic characteristics of these 7 patients. All 7 patients had at least 1 biopsy with a histopathologic pattern compatible with acute AMR. Additionally, we observed accompanied moderately to markedly dilated portal/central veins and endothelialitis disproportionate to the degree of bile duct injury in all 7 patients; periportal/perivenular hepatocyte necrosis was seen in 6 of 7 patients; and arteritis was seen in 3 of 7 patients. In each case, microvascular C4d deposition was present in at least 1 biopsy. Posttransplant donor specific anti-HLA antibodies were detected in 5 patients. Two of 7 patients were retransplanted, and 2 died after developing refractory AMR. The remaining 5 patients were alive with stable graft function at a median follow-up of 4.1 years.

Conclusions.

Our data suggest that acute AMR in pediatric liver grafts is rare, can develop late, and may be associated with graft loss or patient death. The recurrent histopathologic findings of moderately to markedly dilated portal/central veins and endothelialitis disproportionate to the degree of bile duct injury are features that appear unique to pediatric acute AMR of liver grafts.
Long-term Outcomes of Sequential Hematopoietic Stem Cell Transplantation and Kidney Transplantation: Single-center Experience
Authors: Moreira Carla Leal , Hasib Sidiqi M. , Buadi Francis K. , Litzow Mark R. , Gertz Morie A. , Dispenzieri Angela , Russell Stephen J. , Ansell Stephen M. , Stegall Mark D. , Prieto Mikel , Dean Patrick G. , Nyberg Scott L. , El Ters Mireille , Hogan William J. , Amer Hatem , Cosio Fernando G. , Leung Nelson
Published: October 2020

Background.

Experience with sequential hematopoietic stem cell transplant (HSCT) and kidney transplant (KT) is limited.

Methods.

We conducted a retrospective observational study of adult patients who underwent both HSCT and KT at our center, with a median follow-up of 11 y.

Results.

In our 54 patients cohort (94% autologous HSCT), 36 (67%) patients received HSCT first followed by KT, while 18 (33%) received KT before HSCT. In both groups, AL amyloidosis represented 50% of hematologic diagnosis. Only 4 patients expired due to hematologic disease relapse (2 patients in each group) and only 3 allografts were lost due to hematologic disease recurrence (HSCT first n = 1 and KT first n = 2). Overall 1, 5, and 10 y death-censored graft survival rates were 94%, 94%, and 94%, respectively, for the HSCT first group and 89%, 89%, and 75%, respectively, for the KT first group. Overall 1, 5, and 10 y patients survival rates were 100%, 97% and 90%, respectively, for the HSCT first group and 100%, 76%, and 63%, respectively, for the KT first group.

Conclusions.

Our study supports safety of sequential KT and HSCT, with improved overall patient survival compared to recipients of HSCT remaining on dialysis and good long-term kidney allograft outcome.
Month-long Respiratory Support by a Wearable Pumping Artificial Lung in an Ovine Model
Authors: Orizondo Ryan A. , Omecinski Katelin S. , May Alexandra G. , Dhamotharan Vishaal , Frankowski Brian J. , Burgreen Greg W. , Ye Sang-Ho , Kocyildirim Ergin , Sanchez Pablo G. , D’Cunha Jonathan , Wagner William R. , Federspiel William J.
Published: October 2020

Background.

A wearable artificial lung could improve lung transplantation outcomes by easing implementation of physical rehabilitation during long-term pretransplant respiratory support. The Modular Extracorporeal Lung Assist System (ModELAS) is a compact pumping artificial lung currently under development. This study evaluated the long-term in vivo performance of the ModELAS during venovenous support in awake sheep. Feedback from early trials and computational fluid dynamic analysis guided device design optimization along the way.

Methods.

The ModELAS was connected to healthy sheep via a dual-lumen cannula in the jugular vein. Sheep were housed in a fixed-tether pen while wearing the device in a holster during support. Targeted blood flow rate and support duration were 2–2.5 L/min and 28–30 days, respectively. Anticoagulation was maintained via systemic heparin. Device pumping and gas exchange performance and hematologic indicators of sheep physiology were measured throughout support.

Results.

Computational fluid dynamic-guided design modifications successfully decreased pump thrombogenicity from initial designs. For the optimized design, 4 of 5 trials advancing past early perioperative and cannula-related complications lasted the full month of support. Blood flow rate and CO2 removal in these trials were 2.1 ± 0.3 L/min and 139 ± 15 mL/min, respectively, and were stable during support. One trial ended after 22 days of support due to intradevice thrombosis. Support was well tolerated by the sheep with no signs of hemolysis or device-related organ impairment.

Conclusions.

These results demonstrate the ability of the ModELAS to provide safe month-long support without consistent deterioration of pumping or gas exchange capabilities.
DIAGNOSTIC ACCURACY OF A NOCTURIA SINGLE QUESTION SCALE AS A PREDICTOR OF SEVERITY OF LOWER URINARY TRACT SYMPTOMS IN MEN
Authors: Silva Caroline Santos , Bellucci Carlos Henrique Suzuki , de Paula Miranda Eduardo , Alvaia Mateus Andrade , Tiraboschi Ricardo Brianezi , Bastos Netto Jose Murillo , Gomes Cristiano Mendes , de Bessa Junior José
Published: October 2020

Objectives

To evaluated the accuracy of a single question on nocturia to identify men with moderate and severe LUTS.

Methods

We evaluated men aged ≥40 years who presented for medical evaluation at two different urological clinics. They completed the IPSS and the Nocturia Single Question Scale (NSQS). NSQS consists of a single question assessing nocturia frequency ranging from 0 to 4. The severity of LUTS using NSQS (index test) versus IPSS (reference standard) was assessed according to the recommendations of the Standards for Reporting of Diagnostic Accuracy Initiative.

Results

The accuracy of the NSQS to discriminate patients with severe LUTS based on the ROC curve was 75% (CI 95% 73 – 82%; p<0.001).

Conclusion

Patients without nocturia or a single void/night (NSQS <2) have low probability, while NSQS ≥ 3 has a high probability of having moderate or severe LUTS. NSQS is an acceptable alternative to the IPSS, being a fast and simple tool to identify men according to LUTS’s severity.
Scalable, effective, and rapid decontamination of SARS-CoV-2 contaminated N95 respirators using germicidal ultra-violet C (UVC) irradiation device
Authors: Rathnasinghe Raveen , Karlicek Robert F. , Schotsaert Michael , Koffas Mattheos , Arduini Brigitte , Jangra Sonia , Wang Bowen , Davis Jason L. , Alnaggar Mohammed , Costa Anthony , Vincent Richard , Garcia-Sastre Adolfo , Vashishth Deepak , Balchandani Priti
Published: October 2020

Importance

Particulate respirators such as N95 masks are an essential component of personal protective equipment (PPE) for front-line workers. This study describes a rapid and effective UVC irradiation system that would facilitate the safe re-use of N95 respirators and provides supporting information for deploying UVC for decontamination of SARS-CoV-2 during the COVID19 pandemic.

Objective

To assess the inactivation potential of the proposed UVC germicidal device as a function of time by using 3M® 8211 - N95 particulate respirators inoculated with SARS-CoV-2.

Design

A germicidal UVC device to deliver tailored UVC dose was developed and snippets (2.5cm2) of the 3M-N95 respirator were inoculated with 106 plaque-forming units (PFU) of SARS-CoV-2 and were UV irradiated. Different exposure times were tested (0-164 seconds) by fixing the distance between the lamp (10 cm) and the mask while providing an exposure of at least 5.43 mWcm-2.

Setting

The current work is broadly applicable for healthcare-settings, particularly during a pandemic such as COVID-19.

Participants

Not applicable.

Main Outcome(s) and Measure(s)

Primary measure of outcome was titration of infectious virus recovered from virus-inoculated respirator pieces after UVC exposure. Other measures included the method validation of the irradiation protocol, using lentiviruses (biosafety level-2 agent) and establishment of the germicidal UVC exposure protocol.

Results

An average of 4.38×103 PFUml-1(SD 772.68) was recovered from untreated masks while 4.44×102 PFUml-1(SD 203.67), 4.00×102 PFUml-1(SD 115.47), 1.56×102 PFUml-1(SD 76.98) and 4.44×101 PFUml-1(SD 76.98) was recovered in exposures 2s,6s,18s and 54 seconds per side respectively. The germicidal device output and positioning was monitored and a minimum output of 5.43 mWcm-2 was maintained. Infectious SARS-CoV-2 was not detected by plaque assays (minimal level of detection is 67 PFUml-1) on N95 respirator snippets when irradiated for 120s per side or longer suggesting 3.5 log reduction in 240 seconds of irradiation.

Conclusions and Relevance

A scalable germicidal UVC device to deliver tailored UVC dose for rapid decontamination of SARS-CoV-2 was developed. UVC germicidal irradiation of N95 snippets inoculated with SARS-CoV-2 for 120s per side resulted in 100% (3.5 log in total) reduction of virus. These data support the reuse of N95 particle-filtrate apparatus upon irradiation with UVC and supports use of UVC-based decontamination of SARS-CoV-2 virus during the COVID19 pandemic.
Multi-omics highlights ABO plasma protein as a causal risk factor for COVID-19
Authors: Hernández Cordero Ana I. , Li Xuan , Milne Stephen , Yang Chen Xi , Bossé Yohan , Joubert Philippe , Timens Wim , van den Berge Maarten , Nickle David , Hao Ke , Sin Don D.
Published: October 2020

SARS-CoV-2 is responsible for the coronavirus disease 2019 (COVID-19) and the current health crisis. Despite intensive research efforts, the genes and pathways that contribute to COVID-19 remain poorly understood. We therefore used an integrative genomics (IG) approach to identify candidate genes responsible for COVID-19 and its severity. We used Bayesian colocalization (COLOC) and summary-based Mendelian randomization to combine gene expression quantitative trait loci (eQTLs) from the Lung eQTL (n=1,038) and eQTLGen (n=31,784) studies with published COVID-19 genome-wide association study (GWAS) data from the COVID-19 Host Genetics Initiative. Additionally, we used COLOC to integrate plasma protein quantitative trait loci (pQTL) from the INTERVAL study (n=3,301) with COVID-19-associated loci. Finally, we determined any causal associations between plasma proteins and COVID-19 using multi-variable two-sample Mendelian randomization (MR). We found that the expression of 20 genes in lung and 31 genes in blood was associated with COVID-19. Of these genes, only three (LZTFL1, SLC6A20andABO) had been previously linked with COVID-19 in GWAS. The novel loci included genes involved in interferon pathways (IL10RB, IFNAR2andOAS1). Plasma ABO protein, which is associated with blood type in humans, demonstrated a significant causal relationship with COVID-19 in MR analysis; increased plasma levels were associated with an increased risk of having COVID-19 and risk of severe COVID-19. In summary, our study identified genes associated with COVID-19 that may be prioritized for future investigation. Importantly, this is the first study to demonstrate a causal association between plasma ABO protein and COVID-19.
Modulating the Blood-Brain Barrier by Light Stimulation of Molecular-Targeted Nanoparticles
Authors: Li Xiaoqing , Vemireddy Vamsidhara , Cai Qi , Xiong Hejian , Kang Peiyuan , Li Xiuying , Giannotta Monica , Hayenga Heather , Pan Edward , Sirsi Shashank , Mateo Celine , Kleinfeld David , Greene Chris , Campbell Matthew , Dejana Elisabetta , Bachoo Robert , Qin Zhenpeng
Published: October 2020

The blood-brain barrier (BBB) tightly regulates the entry of molecules into the brain by tight junctions that seals the paracellular space and receptor-mediated transcytosis. It remains elusive to selectively modulate these mechanisms and to overcome BBB without significant neurotoxicity. Here we report that light stimulation of tight junction-targeted plasmonic nanoparticles selectively opens up the paracellular route to allow diffusion through the compromised tight junction and into the brain parenchyma. The BBB modulation does not impair vascular dynamics and associated neurovascular coupling, or cause significant neural injury. It further allows antibody and adeno-associated virus delivery into local brain regions. This novel method offers the first evidence of selectively modulating BBB tight junctions and opens new avenues for therapeutic interventions in the central nervous system.

One Sentence Summary

Gentle stimulation of molecular-targeted nanoparticles selectively opens up the paracellular pathway and allows macromolecules and gene therapy vectors into the brain.
Distinct algorithms for combining landmarks and path integration in medial entorhinal, visual and retrosplenial cortex
Authors: Campbell Malcolm G. , Attinger Alexander , Ocko Samuel A. , Ganguli Surya , Giocomo Lisa M.
Published: October 2020

During navigation, animals estimate their position using path integration and landmarks, engaging many brain areas. Whether these areas follow specialized or universal cue integration principles remains unknown. Here, we combined electrophysiology with virtual reality to quantify cue integration across thousands of neurons in three areas that support navigation: primary visual (V1), retrosplenial (RSC) and medial entorhinal cortex (MEC). Path integration influenced position estimates in MEC more than in V1 and RSC. V1 coded position retrospectively, likely reflecting delays in sensory processing, whereas MEC coded position prospectively, and RSC was intermediate between the two. In combining path integration with landmarks, MEC showed signatures of Kalman filtering, and we report a distance-tuned neural population that could implement such filtering through attractor dynamics. Our results show that during navigation, MEC serves as a specialized cortical hub for reconciling path integration and landmarks to estimate position and suggest an algorithm for calculating these estimates.
Comparison of Efficacy of Dexamethasone and Methylprednisolone in Improving the Partial Pressure of Arterial Oxygen and Fraction of Inspired Oxygen Ratio among COVID-19 Patients
Authors: Rana Muhammad Asim , Hashmi Mubashar , Pervaiz Rizwan , Qayyum Ahad , Saleem Muhammad , Munir Muhammad Faisal , Saif Muneeb Ullah
Published: October 2020

Introduction

The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), causing coronavirus disease 2019 (COVID-19), created a pandemic in late 2019. Acute respiratory distress syndrome can occur in patients with COVID-19 due to viral replication and an uncontrolled immune reaction. Therefore, antiviral and anti-inflammatory treatments are of particular interest to clinicians. We compared the efficacy of methylprednisolone and dexamethasone in reducing inflammation and improving the partial pressure of arterial oxygen and fraction of inspired oxygen (PaO2/FiO2 or P/F) ratio in COVID-19 patients.

Methods

We selected 60 files for this retrospective quasi-experimental study using a convenient sampling technique and divided them into two groups of 30 patients each who had received either dexamethasone or methylprednisolone. The data were taken from the medical records of the treated patients. Group 1 patients were given dexamethasone 8 mg twice daily, and Group 2 patients were given methylprednisolone 40 mg twice daily for eight days during their stay in our high dependency unit and our Intensive Care Unit. The remaining treatment was the same for both groups using antibiotics and anticoagulation. We reviewed C-reactive protein (CRP), serum ferritin level, and P/F ratio before and after the administration of both drugs for eight days. We used a paired t-test to assess the effectiveness of both drugs on the P/F ratio of participants.

Results

The initial mean CRP level of Group 1 was 110.34 mg/L, which decreased to 19.45 mg/L after administration of dexamethasone; similarly, the CRP of Group 2 was 108.65 mg/L, which decreased to 43.82 mg/L after administering methylprednisolone for eight days. Both dexamethasone and methylprednisolone significantly improved the P/F ratio (p<0.05), and dexamethasone was significantly more effective than methylprednisolone (p<0.05).

Conclusion

Steroids’ ability to reduce inflammation and suppress the immune response make them an effective tool in the treatment of COVID-19. Steroid therapy is effective in controlling inflammation markers, and, specifically, dexamethasone is effective in improving the P/F ratio in COVID-19 patients. Physicians should consider the use of dexamethasone use in appropriate patients with COVID-19.
System Dynamics Model of Possible Covid-19 Trajectories Under Various Non-Pharmaceutical Intervention Options in a Low Resource Setting
Authors: Lucy Kivuti-Bitok W , S.Abiodun Momodu , Joyce Cheptum Jebet , Fredrick Kimemia , Isaac Gichuki , Irene Ngune
Published: October 2020

We present a population-based System Dynamics Model (SDM) of possible Covid-19 trajectories under various intervention options in the uniqueness of Kenya. We developed a stock and flow based SDM. We parametrized the SDM using published data and where data was not available, expert opinion was sought. Following validation test, the model was simulated to determined possible outcomes of non-pharmaceutical interventions in management of Covid-19. We simulate the possible impact of; social distancing, quarantining, curfew and cross-county travel restriction, lockdown of selected cities in Kenya and quarantining. We varied interventions in terms of start dates, duration of implementation and effectiveness of the interventions. We estimated the outcomes in terms of number of possible infections, recoveries and deaths. With the current state of interventions, we estimated a peak of Covid-19 in September 2020 with an estimated 13.5 Million Covid-19 cases and 33.8 thousand deaths in Kenya. The largest possible reduction in infections and mortality was achievable through increase in the effectiveness of the interventions. The suggested interventions would delay the epidemic peak of Covid-19 to between late Nov 2020 and early December 2020 with an estimated13M cases a 500 thousand reduction in Covid-19 cases and 32.4 deaths (a reduction in 1400 deaths). We conclude that SDM enables understanding of the complexity and impact of different interventions scenarios of Covid-19 in Kenya.
Synthesis and single-molecule imaging reveal stereospecific enhancement of binding kinetics by the antitumor eEF1A antagonist SR-A3
Authors: Wang Hao-Yuan , Yang Haojun , Holm Mikael , Oltion Keely , Tom Harrison , Al-Khdhairawi Amjad Ayad Qatran , Weber Jean-Frédéric F. , Blanchard Scott C. , Ruggero Davide , Taunton Jack
Published: October 2020

Ternatin-family cyclic peptides inhibit protein synthesis by targeting the eukaryotic elongation factor-1α (eEF1A). A potentially related cytotoxic natural product (“A3”) was isolated from Aspergillus, but only 4 of its 11 stereocenters could be assigned. Here, we synthesized SR-A3 and SS-A3 – two out of 128 possible A3 epimers – and discovered that synthetic SR-A3 is indistinguishable from naturally derived A3. Relative to SS-A3, SR-A3 exhibits enhanced residence time and rebinding kinetics, as revealed by single-molecule fluorescence imaging of elongation reactions catalyzed by eEF1A in vitro. Increased residence time – stereospecifically conferred by the unique β-hydroxyl in SR-A3 – was also observed in cells. Consistent with its prolonged duration of action, thrice-weekly dosing with SR-A3 led to dramatically increased survival in an aggressive Myc-driven mouse lymphoma model. Our results demonstrate the potential of SR-A3 as a cancer therapeutic and exemplify an evolutionary mechanism for enhancing cyclic peptide binding kinetics via stereospecific side-chain hydroxylation.
EMPress enables tree-guided, interactive, and exploratory analyses of multi-omic datasets
Authors: Cantrell Kalen , Fedarko Marcus W. , Rahman Gibraan , McDonald Daniel , Yang Yimeng , Zaw Thant , Gonzalez Antonio , Janssen Stefan , Estaki Mehrbod , Haiminen Niina , Beck Kristen L. , Zhu Qiyun , Sayyari Erfan , Morton Jamie , Tripathi Anupriya , Gauglitz Julia M. , Marotz Clarisse , Matteson Nathaniel L. , Martino Cameron , Sanders Jon G. , Carrieri Anna Paola , Song Se Jin , Swafford Austin D. , Dorrestein Pieter C. , Andersen Kristian G. , Parida Laxmi , Kim Ho-Cheol , Vázquez-Baeza Yoshiki , Knight Rob
Published: October 2020

Standard workflows for analyzing microbiomes often include the creation and curation of phylogenetic trees. Here we present EMPress, an interactive tool for visualizing trees in the context of microbiome, metabolome, etc. community data scalable beyond modern large datasets like the Earth Microbiome Project. EMPress provides novel functionality—including ordination integration and animations—alongside many standard tree visualization features, and thus simplifies exploratory analyses of many forms of ‘omic data.
Antinociceptive, hypothermic, and appetitive effects of vaped and injected Δ9-tetrahydrocannabinol (THC) in rats: exposure and dose-effect comparisons by strain and sex
Authors: Moore Catherine F. , Davis Catherine M. , Harvey Eric L. , Taffe Michael A. , Weerts Elise M.
Published: October 2020

Advances in drug vapor exposure systems utilizing e-cigarette technology have enabled evaluation of Δ-9-tetrahydrocannabinol (THC) vapor effects in laboratory animals. The purpose of this study was to 1) establish a range of parameters of THC vapor exposure in rats sufficient to produce a behavioral dose-effect curve in a battery of tasks sensitive to THC; 2) to investigate sex differences in the effects of THC vapor exposure and THC injection (intraperitoneal, IP) on these behaviors in two strains of outbred rats. Male and female Wistar and Sprague Dawley rats (N=22, 5-6/group) received THC via IP injection (1-20 mg/kg) and passive exposure to THC vapor (200 mg/ml; 5 conditions) in a within subject design. The effects of vaped and injected THC were determined using the tail-withdrawal assay for nociception, rectal measurements of body temperature, and progressive-ratio responding for food pellets. Plasma THC concentrations were assessed after 10 mg/kg IP THC or THC vapor. THC produced dose and exposure-dependent antinociception and hypothermia. THC vapor produced inverted U-shaped effects in motivation to obtain food, while IP THC reduced PR breakpoints. Plasma THC concentrations were higher after 10 mg/kg IP THC (152 ng/mL) compared to the highest vapor exposure condition tested (38 ng/mL). THC vapor exposure produces reliable, dose-orderly effects on nociception, body temperature, and food-maintained behavior that is comparable to effects observed after IP THC. There are considerable differences between the time course of behavioral outcomes produced by these two different routes of administration.
Targeting the SHP2 phosphatase promotes vascular damage and inhibition of tumor growth
Authors: Wang Yuyi , Salvucci Ombretta , Ohnuki Hidetaka , Tran Andy D. , Ha Taekyu , Feng Jing-Xin , DiPrima Michael , Kwak Hyeongil , Wang Dunrui , Kruhlak Michael , Tosato Giovanna
Published: October 2020

The tyrosine phosphatase SHP2 is oncogenic in cancers driven by receptor-tyrosine-kinases, and SHP2 inhibition reduces tumor growth. Here, we report that SHP2 is an essential promoter of endothelial cell survival and growth in the remodeling tumor vasculature. Using genetic and chemical approaches to inhibit SHP2 activity in endothelial cells, we show that SHP2 inhibits pro-apoptotic STAT3 and stimulates proliferative ERK1/2 signaling. Systemic SHP2 inhibition in mice bearing tumors selected for SHP2-independent tumor-cell growth, promotes degeneration of the tumor vasculature and blood extravasation; reduces tumor vascularity and blood perfusion; and increases tumor hypoxia and necrosis. Reduction of tumor growth ensues, independent of SHP2 targeting in the tumor cells, blocking immune checkpoints or recruiting anti-tumor macrophages. We also show that inhibiting the Angiopoietin/TIE2/AKT cascade magnifies the vascular and anti-tumor effects of SHP2 inhibition by blocking tumor endothelial AKT signaling, not a target of SHP2. Since the SHP2 and Ang2/TIE2 pathways are active in vascular endothelial cells of human melanoma and colon carcinoma, SHP2 inhibitors alone or with Ang2/Tie2 inhibitors hold promise to effectively target the tumor endothelium.
Can crop phenology and plant height be channelized to improvise wheat productivity in diverse production environments?
Authors: Mohan D , Mamrutha H M , Khobra Rinki , Singh Gyanendra , Singh GP
Published: October 2020

Non-grain parameters like height, flowering and maturity should also be tried to break yield plateau in wheat. This study explores such possibilities by analysing performance of released and pre-released varieties evaluated in ten diverse production environments of India during the period 2000-2020. Regression analysis supports relevance of such non-grain determinants in grain yield under every environment but magnitude of impact can vary. Collective contribution of non-grain parameters can be high in a production environment where growth condition is most favourable for wheat growth and every factor is important in such situations. They contribute less in the environments engrossed with abiotic stress and merely one or two factors can be earmarked for selection. Besides yield, this selection strategy can also enhance grain weight in certain environments. At a time when selection for grain attributes is not providing further push; it would be worth trying to explore these non-grain field indicators as selection strategy for further advancement in productivity and grain weight of bread wheat.
Otx2 stimulates adult retinal ganglion cell regeneration
Authors: Torero-Ibad Raoul , Quenech’du Nicole , Prochiantz Alain , Moya Kenneth L.
Published: October 2020

Retinal ganglion cell axons provide the only link between the light sensitive and photon transducing neural retina and visual centers of the brain. Retinal ganglion cell axon degeneration occurs in a number of blinding diseases and the ability to stimulate axon regeneration from surviving ganglion cells could provide the anatomic substrate for restoration of vision. OTX2 is a homeoprotein transcription factor expressed in the retina and previous studies showed that, in response to stress, exogenous OTX2 increases thein vitroandin vivosurvival of retinal ganglion cells. The present results show that, in addition to promoting adult retinal ganglion cell survival, OTX2 also stimulates the regeneration of their axonsin vitroandin vivo. This dual activity of OTX2 on retinal ganglion cell survival and regeneration is of potential interest for degenerative diseases affecting this cell type.
WITHDRAWN: Multiplane Mesoscope reveals distinct cortical interactions following expectation violations
Authors: Orlova Natalia , Najafi Farzaneh , Tsyboulski Dmitri , Seid Sam , Kivikas Sara , Kato India , Griffin Fiona , Leon Arielle , Hytnen Ross D. , L’Heureux Quinn , North Kat , Swapp Jackie , Nayan Chelsea , Hancock Nicole , Ahmed Ruweida , Gelfand Emily , Cho Andrew , Mace Kyla , Howard Robert , Casal Linzy , Lambert Sophie , Lee Eric Kenji , Caldejon Shiella , Waughman Xana , Williford Allison , Garrett Marina , Ollerenshaw Doug , Olsen Shawn R. , Groblewski Peter A. , Saggau Peter , Lecoq Jérôme
Published: October 2020

Withdrawal Statement

This manuscript has been withdrawn because it was posted without the consent of all authors. Therefore, this work should not be cited as reference for the project. If you have any questions, please contact the corresponding author.