bluuebunny/crossref_metadata_2025 huggingface dataset:
Legislative Design of Director’s Responsibility in India: In Search of Clarity
Authors: Deva Prasad M , Ansari Salamah , Narayan Shannu
Published: November 2020

Indian Companies Act, 2013 addresses the director’s responsibility through specific statutory provisions. While highlighting certain nuances in the legislative design, the article argues for more clarification for the director’s responsibility, specifically for non-executive and independent directors. The normative contribution of this article stresses the need to reform the existing statutory framework for according protection to directors of a company. Operationalization of fiduciary responsibility based on common law principles, along with section 166, Companies Act, 2013 is not clear in the statutory design. Emerging concerns of the director’s responsibility include lack of adequate protection for non-executive and independent directors which deserve more policy deliberations. The recently introduced Insolvency and Bankruptcy Code, 2016 poses evolving responsibility on directors, forming yet another emerging concern in the Indian context.
Obscuring Gendered Difference: The Treatment of Violence in Australian Government Alcohol Policy
Authors: Duncan Duane , Moore David , Keane Helen , Ekendahl Mats
Published: November 2020

Despite public debate about alcohol and public violence among young people in Australia, the issue of masculinities or gender is rarely visible in alcohol policy. Instead, policy recommendations aimed at reducing violence focus on changing the availability and consumption of alcohol. Drawing on concepts from feminist and science and technology studies scholarship, this article analyses how “alcohol-related violence” is constituted as a specific policy object, and how it coheres to obscure men’s contributions to and experiences of violence. Attention to the political effects of these policy practices is necessary for the development of more equitable alcohol policies.
Phytol, a Constituent of Chlorophyll, Induces Root-Knot Nematode Resistance in Arabidopsis via the Ethylene Signaling Pathway
Authors: Fujimoto Taketo , Abe Hiroshi , Mizukubo Takayuki , Seo Shigemi
Published: November 2020

Root-knot nematodes (RKNs; Meloidogyne spp.) parasitize the roots or stems of a wide range of plant species, resulting in severe damage to the parasitized plant. The phytohormone ethylene (ET) plays an important role in signal transduction pathways leading to resistance against RKNs. However, little is currently known about the induction mechanisms of ET-dependent RKN resistance. Inoculation of Arabidopsis thaliana roots with RKNs decreased chlorophyll contents in aerial parts of the plant. We observed accumulation of phytol, a constituent of chlorophyll and a precursor of tocopherols, in RKN-parasitized roots. Application of sclareol, a diterpene that has been shown to induce ET-dependent RKN resistance, to the roots of Arabidopsis plants increased phytol contents in roots accompanied by a decrease in chlorophyll in aerial parts. Exogenously applied phytol inhibited RKN penetration of roots without exhibiting nematicidal activity. This phytol-induced inhibition of RKN penetration was attenuated in the ET-insensitive Arabidopsis mutant ein2-1. Exogenously applied phytol enhanced the production of α-tocopherol and expression of VTE5, a gene involved in tocopherol production, in Arabidopsis roots. α-Tocopherol exerted induction of RKN resistance similar to that of phytol and showed increased accumulation in roots inoculated with RKNs. Furthermore, the Arabidopsis vte5 mutant displayed no inhibition of RKN penetration in response to phytol. These results suggest that exogenously applied phytol induces EIN2-dependent RKN resistance, possibly via tocopherol production.

[Formula: see text] Copyright © 2021 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license .
Genome Sequence Resource of ‘Candidatus Liberibacter asiaticus’ from Diaphorina citri Kuwayama (Hemiptera: Liviidae) from La Réunion
Authors: Lu Jinming , Delatte Hélène , Reynaud Bernard , Beattie George A. C. , Holford Paul , Cen Yijing , Wang Yanjing
Published: November 2020

‘Candidatus Liberibacter asiaticus’ is an insect-transmitted, phloem-restricted α-proteobacterium associated with huanglongbing. Here, we provide the whole genome sequence of ‘Ca. L. asiaticus’ strain ReuSP1 from its insect vector Diaphorina citri (Hemiptera: Liviidae) collected in La Réunion. The genome is composed of 1,230,064 bp and has a 36.5% G+C content. This study reports the first ‘Ca. L. asiaticus’ genome sequence from La Réunion, which will add to ‘Ca. L. asiaticus’ genome resources and help elucidate our understanding of the introduction pathway into La Réunion.
Geographic Distribution and Host Range of Lethal Bronzing Associated with Phytoplasma Subgroup 16SrIV-D on Palms in Southern Louisiana
Authors: Ferguson Mary Helen , Singh Raghuwinder , Cook Madeline , Burks Timothy , Ong Kevin
Published: November 2020

Lethal bronzing (LB), also previously known as date palm lethal decline or Texas Phoenix palm decline, associated with phytoplasma subgroup 16SrIV-D, was first identified in Louisiana in December 2013. A survey of palms showed that the disease was not only confined to City Park in New Orleans, where it was first detected, but is present in other parts of Orleans Parish, as well as two adjacent parishes. Canary Island date palms (Phoenix canariensis) tested positive at the highest frequency, and some edible date palms (P. dactylifera) and a small proportion of cabbage palms (Sabal palmetto) tested positive as well. Symptoms do not appear to be a reliable indicator of LB, because a substantial proportion of palms indicated as symptomatic tested negative. Furthermore, not all infected palms showed symptoms. Since the palm survey conducted in 2015 to 2016, LB has positively been identified from silver date palm (P. sylvestris) and Chinese windmill palm (Trachycarpus fortunei) in three additional parishes in Louisiana.
Rapid Detection of the Laurel Wilt Pathogen in Sapwood of Lauraceae Hosts
Authors: Parra Pedro Pablo , Dantes Wanita , Sandford Amanda , de la Torre Carlos , Pérez José , Hadziabdic Denita , Schaffer Bruce , Gazis Romina
Published: November 2020

Laurel wilt (LW), caused by Raffaelea lauricola (RL), is a vascular fungal disease affecting species in the Lauraceae that has rapidly spread across the United States. This disease has caused significant tree losses in natural forests and Florida’s commercial avocado orchards. RL spreads through ambrosia beetle vectors and root grafts. Early detection and eradication are recommended to contain outbreaks. Therefore, rapid diagnosis is key for the timely implementation of mitigation strategies. Current LW diagnosis can take up to 10 days and involves pathogen isolation and the amplification of two microsatellite regions. To reduce diagnosis time, we optimized the standard PCR-based detection technique and assessed its potential use in the testing of woody samples. We further screened the microsatellite primers IFW and CHK on a higher number of fungal taxa as well as 11 host genotypes. Sensitivity was evaluated using RL-DNA at different concentrations in pure and mixed solutions. There was no cross-amplification in non-RL species. Both primers amplified all tested RL strains (100); however, the IFW primers were more sensitive than the CHK primers. Using the IFW primers, we detected RL in 89% of sapwood samples (76/85). This protocol provides a rapid and effective molecular-based approach that reduces the diagnostic time from 10 days to 24 h. This method can be an important tool for diagnostic laboratories. Altogether, our data and fungal collection, represent a robust foundation for future transferability of this protocol to more sensitive detection technologies (qPCR, LAMP) and for its application to samples from diverse origin (beetles, roots).
Lateral Distractor Use During Internal Fixation of Tibial Plateau Fractures Has a Minimal Risk of Iatrogenic Peroneal Nerve Palsy
Authors: Chen Michael J. , Salazar Brett P. , Tigchelaar Seth S. , Frey Christopher S. , DeBaun Malcolm R. , Goodnough L. Henry , Bellino Michael J. , Bishop Julius A. , Gardner Michael J.
Published: November 2020

Objectives:

To determine the incidence of iatrogenic peroneal nerve palsy after application of an intraoperative lateral distractor during open reduction and internal fixation of tibial plateau fractures.

Design:

Retrospective review.

Setting:

Single academic Level I trauma center.

Patients:

One hundred forty-seven patients met criteria and were included in the study.

Intervention:

Patients with unicondylar and bicondylar tibial plateau fractures underwent open reduction and internal fixation and received application of an intraoperative lateral distractor to aid in visualization and reduction of the impacted lateral plateau.

Main Outcome Measurements:

Incidence of iatrogenic peroneal nerve palsy.

Results:

There was a 2.0% incidence of iatrogenic peroneal nerve symptoms (3 of 147 patients), most of which were incomplete sensory deficits. There was no association with staged external fixation, regional anesthesia, or tourniquet use.

Conclusion:

Use of an intraoperative lateral distractor is safe and has a low incidence of iatrogenic peroneal nerve palsy if applied carefully.

Level of Evidence:

Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.
Closed reduction by trans-physealantegrade elastic stable intramedullary nailing in acute pediatric Monteggia fractures: a report of 22 cases
Authors: Louahem Djamel , Jeandel Clément , Aldugman Tariq , Joly-Monrigal Pauline , Cottalorda Jérôme , Delpont Marion
Published: November 2020

Treatment of acute pediatric Monteggia fractures is still debated. The aim of this study was to assess the efficacy of strategy based on closed reduction by trans-physeal antegrade elastic stable intramedullary nailing (ESIN) of the ulnar fracture. Retrospective analysis of 22 patients (13 boys and nine girls) treated for acute Monteggia fractures between May 2008 and August 2018 was performed. Mean age at injury was 6.6 years. Mean follow-up was 4.5 years. On the basis of the Bado classification, 15 lesions were of type I, three types III and four types IV. All the patients were managed with closed reduction and ESIN of the ulna fracture within 2–19 h of arrival. Intraoperative stability of reduction of the radial head was checked under fluoroscopic control in pronation and supination. Outcomes were assessed with the Bruce et al. scoring system. Closed alignment of the ulnar fracture by ESIN had simultaneously reduced and stabilized the radial head dislocation in all patients. At the final follow-up, all the patients had excellent results. Complete healing of the fracture occurred in 6 weeks and the elastic nail removed at 3–6 months postoperatively. There was no case of instability or subluxation or re-dislocation of the radial head. No olecranon epiphysiodesis or growth disorders were noticed. Early diagnosis and management of acute pediatric Monteggia fractures by closed reduction and ESIN achieve excellent clinical and radiographic outcomes.
Surgical management of invasive fungal infections in adult leukemia patients: experience from a large tertiary center in Southeast-Asia
Authors: Keng Bryan M.H. , Ng Zhi Xuan , Tan Yan Chin , Tan Thuan Tong , Wong Gee Chuan , Nagarajan Chandramouli
Published: November 2020

Objectives:

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in acute leukemia patients undergoing chemotherapy or hematopoietic stem cell transplantation (HSCT). Surgical interventions may be necessary to improve the survival outcomes of these patients. The aim of this study is to report a single-center experience using surgical intervention as adjunctive treatment for IFI in adult leukemia patients.

Methods:

A retrospective review was conducted to obtain clinical characteristics and outcomes of surgically managed IFI patients diagnosed between January 2005 and December 2015 in our center.

Results:

Nineteen acute leukemia patients, median age 46 years (range 19–65), underwent 20 surgical procedures as management for IFI. Three patients had proven IFI diagnoses prior to surgery. Sixteen patients underwent surgery for both diagnostic and therapeutic purposes. Post-surgery, the diagnostic yield for proven IFI increased by a factor of 5, and 15 patients had definitive IFI diagnoses. Surgical complications included 2 pleural effusions, 4 pneumothoraxes, and 1 hydropneumothorax. The median duration of hospitalization for patients with complications was 9 days (range 3–64). Thirteen patients benefited overall from the procedure, 3 had temporary clinical benefits, and 2 had progression of IFI. After surgery, the 3-month and 2-year overall survival rates were 89.5% and 57.9%, respectively. The median time from surgery to resumption of chemotherapy or HSCT was 25 days.

Conclusions:

Surgical interventions for IFI are feasible in selected leukemia patients, as they yield valuable information to guide antifungal therapy or enable therapeutic outcomes with acceptable risk, thereby allowing patients to proceed with curative chemotherapy and HSCT.
CAR-NK cell therapeutics for hematologic malignancies: hope is on the horizon
Authors: Xu Kai-lin , Cheng Hai
Published: November 2020

Chimeric antigen receptor (CAR)-T-cell therapy has achieved significant success in the treatment of hematologic malignancies. However, treatment-related toxicity and side effects remain the major drawbacks. As an important effector cell in innate immunity, natural killer (NK) cells exert strong antitumor functions and have better application prospects in the immunotherapy of hematologic malignancies. Compared with T cells, NK cells exhibit several advantages such as MHC-independent recognition. CAR-modified NK (CAR-NK) cells may exhibit a better ability of killing tumor cells. Herein, we review mainly preclinical data related to the development of CAR-NK cells in treating blood cancers.
Inflamm-aging of hematopoietic stem cells
Authors: Chen Zhiyang , Ju Zhenyu
Published: November 2020

Hematopoietic stem cells (HSCs) are responsible for generating all blood cells throughout life. Apart from the role of HSCs in maintaining the homeostasis of blood cell production process, they must respond quickly to hematopoietic challenges, such as infection or blood loss. HSCs can be directly/indirectly activated and engage in blood formation for the acute needs in response to inflammation. Recent findings highlight the emerging role of inflammation signaling on HSC fate decision and shaping the hematopoietic system during aging. Here, we summarize recent studies identifying the changes in inflammation and their role in modulation of HSC function and discuss the interaction between inflammation and HSC biology in the contexts of aging and hematological malignancy.
PML nuclear body biogenesis and oligomerization-driven leukemogenesis
Authors: Li Yuwen , Ma Xiaodan , Meng Guoyu
Published: November 2020

PML nuclear bodies (NBs), which are increasingly recognized as the central hub of many cellular signaling events, are superassembled spherical complexes with diameters of 0.1–2 μm. Recent studies reveal that RING tetramerization and B1-box polymerization are key factors to the overall PML NBs assembly. The productive RBCC oligomerization allows subsequent PML biogenesis steps, including the PML auto-sumoylation and partners recruitment via SUMO–SIM interactions. In promyelocytic leukemia, the oncoprotein PML/RARα (P/R) inhibits PML NBs assembly and leads to a full-fledged leukemogenesis. In this review, we review the recent progress in PML and acute promyelocytic leukemia fields, highlighting the protein oligomerization as an important direction of future targeted therapy.
T cell regeneration: an update on progress and challenges
Authors: Guo Rongqun , Wu Hongling , Du Juan , Wang Jinyong
Published: November 2020

T cells play essential roles in antitumor therapy. Via gene engineering technique to enhance tumor-antigen specificity, patient peripheral blood-derived T cells (PBT) show encouraging clinical outcomes in treating certain blood malignancies. However, the high costs, functionality exhaustion, and disease-condition-dependent availability of PBT prompt the attempts of exploring alternative T cell sources. Theoretically, induced T cells from pluripotent stem cells (PSC) are ideal candidates that integrate plenty of advantages that primary T cells lack, including unlimited off-the-shelf cell source and precision gene editing feasibility. However, researchers are still struggling with developing a straightforward protocol to induce functional and immunocompetent human T cells from PSC. Based on stromal cell-expressing or biomaterial-presenting Notch ligands DLL1 or DLL4, natural and induced blood progenitors can differentiate further toward T lineage commitment. However, none of the reported T induction protocols has yet translated into any clinical application, signaling the existence of numerous technical barriers for regenerating T cells functionally matching their natural PBT counterparts. Alternatively, new approaches have been developed to repopulate induced T lymphopoiesis via in vivo reprogramming or transplanting induced T cell precursors. Here, we review the most recent progress in the T cell regeneration field, and the remaining challenges dragging their clinical applications.
Antibody-drug conjugates: an evolving approach for melanoma treatment
Authors: Anderson Trevor S. , Wooster Amanda L. , La-Beck Ninh M. , Saha Dipongkor , Lowe Devin B.
Published: November 2020

Melanoma continues to be an aggressive and deadly form of skin cancer while therapeutic options are continuously developing in an effort to provide long-term solutions for patients. Immunotherapeutic strategies incorporating antibody-drug conjugates (ADCs) have seen varied levels of success across tumor types and represent a promising approach for melanoma. This review will explore the successes of FDA-approved ADCs to date compared to the ongoing efforts of melanoma-targeting ADCs. The challenges and opportunities for future therapeutic development are also examined to distinguish how ADCs may better impact individuals with malignancies such as melanoma.
The first 6 months of HIV-SARS-CoV-2 coinfection: outcomes for 6947 individuals
Authors: Johnston Rowena
Published: November 2020

Purpose of review

The aim of this review is to summarize the clinical outcomes of people living with HIV (PWH) coinfected with SARS-CoV-2 during the first six months of the COVID-19 pandemic.

Recent findings

Several reports from single centers have described increased, decreased, or no difference in outcomes of COVID-19 in PWH. These studies have come from a range of locations, each with different underlying HIV prevalence and access to various antiretroviral therapy (ART) regimens. Differences in healthcare quality, access and policies may also affect reported outcomes in PWH across different locations, making interpretation of results more challenging. Meanwhile, different components of ART have been proposed to protect against SARS-CoV-2 acquisition or disease progression.

The current review considers 6 months of data across geographic regions with a range of healthcare quality and access and ART regimens to generate a wider view of COVID-19 outcomes in PWH. Taken together, these studies indicate that HIV infection may be associated with increased risk of COVID-19 diagnosis, but comorbidities appear to play a larger role than HIV-specific variables in outcomes of COVID-19 among PWH. ART does not appear to protect from COVID-19 disease acquisition, progression or death.
Herpes Simplex Virus Infection in Infants
Authors: Berkhout Angela , Kapoor Vishal , Heney Claire , Jones Cheryl A. , Clark Julia E. , Vaska Vikram L. , Lai Melissa , Nourse Clare
Published: November 2020

Background:

National neonatal surveillance for herpes simplex virus (HSV) disease suggests that the incidence of HSV disease may be higher in Queensland (QLD) than in other Australian States. We sought to investigate the incidence via a retrospective 13-year evaluation of statewide laboratory data, autopsy data and linked clinical records of infants with laboratory confirmed infection.

Methods:

All positive polymerase chain reaction HSV 1 and 2 results were obtained for infants 0–3 months of age from January 1, 2005 to December 31, 2017. Clinical data were obtained from patient records and parent questionnaires were used to evaluate long-term sequelae.

Results:

One hundred seventy-two infants with HSV positive polymerase chain reaction results: 121 (70.3%) with HSV 1. Of 104 (60.5%) infants with signs of HSV disease, 76 (73.1%) were neonates (≤28 days of age) [incidence 9.6 (95% confidence interval, 7.0–11.5) per 100,000 live births] and 28 (26.9%) were young infants (29–90 days of age) [3.6 (95% confidence interval, 2.4–5.4) per 100,000 live births]. The annual incidence of neonatal HSV disease increased significantly in Queensland over the study period (P < 0.01). Of the 76 neonates with HSV disease, 58 (76.3%) presented with the skin, eye, mouth (SEM) disease, 17 (22.4%) with HSV encephalitis and 11 (14.5%) had disseminated disease. Young infants presented with HSV skin, eye, mouth disease (21, 75.0%) or HSV encephalitis (6, 21.4%). Death occurred in 12/104 (11.5%) infants (all neonates) with 10 attributable to HSV disease.

Conclusion:

The incidence of neonatal HSV disease in QLD is almost 3 times the national reported incidence. Further research is being undertaken to explore reasons for this change and implications for practice.
In-Season Management of Anterior Shoulder Instability
Authors: Yow Bobby G. , Dickens Jonathan F.
Published: November 2020

Anterior shoulder instability commonly occurs in young and active individuals, particularly those participating in contact or collision sports. At the intercollegiate level, rates of anterior instability have been reported to be 0.12 events per 1000 athlete exposures. The treatment of in-season athletes with anterior instability presents a challenge for the team physician. The desire to return to play within the same season with nonoperative management must be weighed against the increased risk of recurrence as well as athlete and team specific demands. The purpose of this chapter is to discuss the key considerations for the management of the athlete with anterior shoulder instability that occurs within the competitive season.
The Role of Remplissage in the Setting of Shoulder Instability
Authors: Cable Brian , Boniello Michael , Kelly Ann M. , Kelly John D.
Published: November 2020

Recurrent anterior shoulder instability is a multifactorial problem for which many solutions exist. Often, the bony surface area of the humeral head and the glenoid needs to be addressed surgically. For large, engaging humeral head defects associated with <25% glenoid bone loss, a remplissage procedure can effectively “fill in” the humeral defect with minimal postoperative morbidity. Remplissage is an effective biological solution that should be considered any time there is a humeral head defect which is contributing to glenohumeral instability.
Measuring Bone Loss in the Unstable Shoulder: Understanding and Applying the Track Concept
Authors: Di Giacomo Giovanni , de Gasperis Nicola
Published: November 2020

An interesting international debate has been developed over the past 10 years (the last decade) surrounding the surgical procedure for recurrent anteroinferior instability and a definitive consensus is lacking on the factors which favor one technique over another, especially when bone loss is present (soft tissue vs. bone block). Glenoid bone loss is commonly observed in the shoulder with anterior instability, and it is difficult to evaluate the shape of the glenoid using plain radiograph, therefore, computed tomography or intraoperative observation is recommended for accurate assessment of glenoid bone loss and Hill-Sachs lesion. When we consider the bony defect of the glenoid as a risk factor for surgical failure, it is crucial to take into consideration the features of a concomitant Hill-Sachs lesion. However, all the previous reports focusing on the size of the Hill-Sachs lesion or on the glenoid bone loss in isolation, overlook the interaction of the 2 lesions through the arc of range of motion and how this may influence instability. The glenoid track is the first model to determine, in a dynamic way, how bone loss on both sides of the joint can lead to instability. The glenoid track is a zone of contact created by the glenoid on the humeral articular surface when the arm is moved along the end-range of motion (abduction and external rotation). The use of the glenoid track concept can potentially help guide surgical decision-making.
Reduced Spread of Electric Field After Surgical Removal of Intracochlear Schwannoma and Cochlear Implantation
Authors: Wagner Luise , Plontke Stefan K. , Fröhlich Laura , Rahne Torsten
Published: November 2020

Objective:

The primary aim of the study was to explore whether reduced spread of electrical field is observed after partial or subtotal cochleoectomy and cochlear implantation compared with standard cochlear implantation. Secondarily, the influence on speech perception was explored comparing both groups.

Study Design:

Nonconcurrent cohort study.

Setting:

Monocentric study at a tertiary referral center.

Patients:

Twenty adult cochlear implant (CI) users after tumor resection with cochleoectomy of varying extent and 20 electrode-matched CI users with standard electrode insertion.

Interventions:

Partial and subtotal cochleoectomy for tumor removal and CI.

Outcome Measures:

Trans-impedance, electrically evoked compound action potentials, and word recognition were measured. Relative impedance was computed as a function of distance between the stimulation and recording electrode.

Results:

Trans-impedance was smaller and more homogeneous in patients with partial or subtotal cochleoectomy than in the control group. In the tumor group, the mean relative impedance decreased to 0.20 (standard deviation [SD] = 0.03) at a distance of 1 electrode and to 0.25 (SD = 0.04) in the control group. After excluding seven patients with a second tumor in the internal auditory canal or cerebellopontine angle, with transmodiolar tumors, after near total cochleoectomy, or only extended cochleostomy, word recognition was 61% (SD = 19%) at 3 months and 75% (SD = 19%) at 12 months after activation of the audio processor in the tumor group. At 12 months, it was significantly (p < 0.05) better than in the control group (3 mo: 45%, SD = 25%; 12 mo: 53%, SD = 26%). A smaller trans-impedance is associated with a better word recognition.

Conclusion:

We conclude that the surgical technique used for CI surgery after subtotal cochleoectomy reduces the spread of the electric field and overcomes the potential drawbacks in structure preservation associated with that technique.
A Journey Through 100 Years of Vestibular Schwannoma Surgery at Mayo Clinic: A Historical Illustrative Case Series
Authors: Huang Alice E. , Marinelli John P. , Link Michael J. , Boes Christopher J. , Carlson Matthew L.
Published: November 2020

The present state of vestibular schwannoma (VS) management is the product of over a century of technical progress by revolutionary surgeons who transformed a once perilous operation. At the beginning of the 1900s, patients who did not succumb to their disease were treated exclusively with surgery, which itself was almost assuredly devastating. Through the pioneering work of surgeons such as Harvey Cushing, Walter Dandy, William House, and others, safer surgical approaches were established with concurrent advances in neuromonitoring, neuroanesthesia, radiology, and adoption of the operating microscope. Owing to refinements in radiosurgical treatment and a greater understanding of the natural history of disease, there has been a dramatic shift toward more conservative management in recent years. For more than 100 years, the Mayo Clinic in Rochester, MN, has maintained an active and uninterrupted VS practice with activities that are well documented and preserved through the Mayo Clinic historical archives. We herein report representative early cases to illustrate the fascinating evolution in VS surgery over the past century at a single-tertiary referral center. Original clinical, imaging, pathology, and operative reports are presented from each era of management. To accurately portray the medical context of each era, antiquated terminology is intentionally preserved as originally transcribed.
Evolving Role of Non-Total Resection in Management of Acoustic Neuroma in the Gamma Knife Era
Authors: Luryi Alexander L. , Kveton John F. , Babu Seilesh , Bojrab Dennis I. , Michaelides Elias M. , Schutt Christopher A.
Published: November 2020

Objective:

To examine patients with residual tumor after vestibular schwannoma (VS) resection with focus on need for further therapy, including stereotactic radiosurgery (SRS) and revision surgery.

Study Design and Setting:

Retrospective review at two tertiary otology referral centers.

Patients and Intervention:

Patients undergoing primary surgery for VS from 2007 to 2017.

Main Outcome Measure:

Degree of resection and need for further treatment.

Results:

Of 289 patients undergoing surgery, 38 (13.1%) underwent subtotal resections (<95% of tumor resected) and 77 (26.6%) underwent near-total resections (≥95% but <100%). Patients with any residual tumor had larger tumors preoperatively (mean estimated volume 6.3 cm3 versus 2.1 cm3, p < 0.0005) but were otherwise clinically and demographically similar to the population as a whole. Further treatment (surgery or SRS) was needed in 4.6, 14.3, and 50.0% of patients after gross total, near-total, and subtotal resections, respectively (p < 0.0005). Patients undergoing additional therapy had larger residual tumors (median post- to preoperative estimated volume ratio 0.09 versus 0.01, p < 0.0005). Patients undergoing subtotal and near-total resections had poorer facial function at ultimate follow up than those undergoing gross total resections (p = 0.001), likely due to larger tumors and more difficult resections. Literature review revealed higher rates of gross total resection as well as facial palsy in the pre-SRS era.

Conclusion:

Residual tumor following VS resection is more common today than in the pre-SRS era. Availability of SRS may encourage leaving residual tumor intraoperatively to preserve neural structures. Current surgical strategies decrease surgical morbidity but necessitate further treatment in over 10% of cases.
Evaluation of the Effectiveness of In‐line Immobilized Lipase Cartridge in Enterally Fed Patients With Cystic Fibrosis
Authors: Sathe Meghana N. , Patel Dhiren , Stone Archie , First Eric
Published: November 2020

Background:

Pancreatic insufficiency occurs in most patients with cystic fibrosis (CF) contributing to malnutrition. In the United States, 3600 patients with CF require enteral feeding (EF). Oral pancreatic enzymes are commonly used with EF, despite not being designed or approved for this use. An immobilized lipase cartridge (ILC) for extracorporeal digestion of enteral feedings was developed. The sponsor provided it to patients via a structured program, which we evaluated to assess the effectiveness of the ILC on nutritional status.

Methods:

The program provided the ILC to patients prescribed the device while reimbursement efforts were ongoing. Baseline anthropometric data were obtained and subsequent measurements of height, weight, and body mass index (BMI) were collected at 6 and 12 months.

Results:

Inclusion criteria were met by 100 patients (age = 0‐‐45 years). Over 12 months of use in patients >2 years of age (n = 93), there were significant improvements seen in height and weight z‐scores with improvement trend seen in BMI. The frequency of achieving the 50th percentile increased steadily for weight and BMI from baseline to 12 months but not for height.

Conclusions:

This evaluation of a program to assist patient access to ILC demonstrates that better growth is possible over standard of care. The association of ILC use with significant improvements in anthropometric parameters over a 12‐month period in people with CF demonstrates the effectiveness of ILC as rational enzyme therapy during enteral feedings.
Pharmacological Treatment for Comorbid Bipolar Disorder and Obsessive-Compulsive Disorder in Adults
Authors: NETTO VITOR DE MELLO , FLORES CAROLINA A. , PALLANTI STEFANO
Published: November 2020

Comorbidity between bipolar disorder (BD) and obsessive-compulsive disorder (OCD) is fairly common, and the treatment of these conditions when comorbid is challenging. Serotonin reuptake inhibitors, the first option for treatment of OCD, can worsen BD symptoms, and mood stabilizers are generally not efficacious for OCD. Our goal in this article is to assess the clinical effectiveness of pharmacotherapies for comorbid BD-OCD in adults. We searched the Medline, Embase, and Cochrane Central Register of Controlled Trials databases on April 30, 2017, and we also searched the reference lists of identified articles. Studies published beginning January 1, 2007 were included, without language restrictions. Narrative and systematic reviews, letters to the editor, and book chapters were excluded. Two authors independently assessed the quality of the studies and extracted data. Seven studies met our inclusion criteria. Findings from double-blind, randomized, placebo-controlled trials were pooled for analysis. Findings from this pooled analysis indicated that augmentation of mood-stabilizer treatment with glutamate modulator agents (topiramate or memantine) may favor full response of obsessive-compulsive symptoms (risk ratio: 2.62, 95% confidence interval: 1.45-4.74) in patients with BD type I and OCD in the manic phase, and that it does not significantly induce adverse effects (risk ratio: 1.26, 95% confidence interval: 0.53-3.01). Results of a narrative synthesis of observational studies indicated greater efficacy of mood-stabilizer treatment, with serotonin reuptake inhibitors less used. Findings from studies employing different designs were not compared, and our results should be interpreted cautiously.
Blue Monday: Co-occurring Stimulant Use and HIV Persistence Predict Dysregulated Catecholamine Synthesis
Authors: Chahine Antonio , Koru-Sengul Tulay , Feaster Daniel J. , Dilworth Samantha E. , Antoni Michael H. , Klatt Nichole , Roach Margaret E. , Pallikkuth Suresh , Sharkey Mark , Salinas Jessica , Stevenson Mario , Pahwa Savita , Fuchs Dietmar , Carrico Adam W.
Published: November 2020

Background:

This longitudinal study examined whether co-occurring stimulant use and HIV disease processes predicted greater risk for depression via dysregulated metabolism of amino acid precursors for neurotransmitters.

Methods:

In total, 110 sexual minority men (ie, gay, bisexual, and other men who have sex with men) living with HIV who had biologically confirmed recent methamphetamine use were enrolled in a randomized controlled trial. The kynurenine/tryptophan (K/T) and phenylalanine/tyrosine (P/T) ratios were measured over 15 months to index dysregulated metabolism of amino acid precursors for serotonin and catecholamines. Markers of gut-immune dysregulation such as lipopolysaccharide binding protein and soluble CD14 (sCD14), HIV persistence in immune cells (ie, proviral HIV DNA), and stimulant use were examined as predictors. These bio-behavioral measures, including the K/T and P/T ratios, were also examined as predictors of greater risk for depression over 15 months.

Results:

Higher time-varying sCD14 levels (β = 0.13;P= 0.04) and time-varying detectable viral loads (β = 0.71;P< 0.001) were independent predictors of a higher K/T ratio. Time-varying reactive urine toxicology results for stimulants (β = 0.53;P< 0.001) and greater proviral HIV DNA at baseline (β = 0.34;P< 0.001) independently predicted an increased P/T ratio. Greater time-varying, self-reported methamphetamine use uniquely predicted higher odds of screening positive for depression (Adjusted Odds Ratio = 1.08; 95% confidence interval: 1.01 to 1.17).

Conclusions:

Ongoing stimulant use and HIV persistence independently predict dysregulated metabolism of amino acid precursors for catecholamines, but this did not explain amplified risk for depression.
Smooth Muscle Conditions of the Chest
Authors: McCann Matthew R. , Massoth Lucas R. , Rojas Carlos A. , Hung Yin P. , Lichtenberger John P. , Abbott Gerald F. , Stowell Justin T.
Published: November 2020

Smooth muscle conditions of the chest have diverse clinical and imaging manifestations and may involve nearly every thoracic structure. Differentiation among these conditions requires the integration of clinical, radiologic, and histopathologic data. Histologic examination in conjunction with immunohistochemistry is essential for differentiation from other spindle cell neoplastic mimics. Familiarity with these entities will ensure the inclusion of smooth muscle conditions in the differential diagnosis of thoracic soft tissue lesions and potentially guide the clinician in appropriate management. We review the clinical, imaging, and histopathologic features of thoracic smooth muscle-related conditions organized by the anatomic structures affected.
Hybrid emergency room shows maximum effect on trauma resuscitation when used in patients with higher severity
Authors: Umemura Yutaka , Watanabe Atsushi , Kinoshita Takahiro , Morita Natsuhiro , Yamakawa Kazuma , Fujimi Satoshi
Published: November 2020

BACKGROUND

The hybrid emergency room (ER) system is a novel trauma workflow that uses angio–computed tomography equipment in a trauma resuscitation room. Although the hybrid ER system decreases time to start surgery and endovascular treatments and improves mortality, the optimal target benefitting from this system remained unclear. We aimed to identify a subset of trauma patients likely to receive the greatest benefits from the hybrid ER.

METHODS

This retrospective cohort study was conducted in a tertiary hospital in Japan from August 2007 to January 2020. We consecutively included severe adult blunt trauma patients (Injury Severity Score [ISS], ≥16) and divided them into two groups: conventional group (August 2007 to July 2011) and hybrid ER (August 2011 to January 2020) group. We evaluated the association between the hybrid ER group and 28-day mortality using multivariable logistic regression analysis. The 28-day mortality trend during the study period was evaluated with restricted cubic spline analysis. To evaluate heterogeneity of effects within various patient severities, we evaluated whether the patients’ ISS modified the effect of the hybrid ER on survival.

RESULTS

Among 1,050 trauma patients, the conventional group comprised 360 patients and the hybrid ER group comprised 690 patients. Injury Severity Score and probability of survival (Ps) were not significantly different between the groups. Twenty-eight-day mortality was significantly lower in the hybrid ER group (Ps-adjusted odds ratio, 0.48; 95% confidence interval, 0.32–0.71; p < 0.001). Restricted cubic spline analysis revealed that Ps-adjusted 28-day mortality sharply decreased approximately 200 days after installation of the hybrid ER. Increase of survival probabilities according to the increase of ISS was significantly improved in hybrid ER group (p = 0.014). Because ISS increased to >25, survival probabilities in the hybrid ER group were higher compared with those in the conventional group.

CONCLUSION

The hybrid ER may improve posttraumatic mortality, especially in patients with higher baseline severity.

LEVEL OF EVIDENCE

Therapeutic/care management, level IV.
Nicotine induces P2X4 receptor, interleukin-1 beta, and brain-derived neurotrophic factor expression in BV2 microglia cells
Authors: Guo Lina , Zhang Yang , Lv Qing , Zhang Zongwang
Published: November 2020

Objective

Upregulation of P2X4 receptor (P2X4R), brain-derived neurotrophic factor (BDNF), and interleukin-1 beta (IL-1β) in activated microglia is associated with hyperalgesia. This study investigated whether nicotine increases pain hypersensitivity by altering the expression of these molecules in microglia. We also examined the role of interferon regulatory factor 8 (IRF8) in this process.

Methods

Experiments were performed in BV2 microglial cells. IRF8 was knocked down or overexpressed using lentiviruses harboring a short hairpin RNA targeting IRF8 or an IRF8 overexpression construct, respectively. P2X4R, BDNF, and IL-1β mRNA and protein levels were evaluated by real-time PCR and western blotting, respectively, and BDNF and IL-1β secretion was assessed by ELISA.

Results

Chronic nicotine exposure enhanced the expression of P2X4R, BDNF, and IL-1β in BV2 cells, and stimulated the release of BDNF and IL-1β in the presence of ATP. IRF8 was found to mediate the nicotine-induced increases in BDNF and IL-1β mRNA and P2X4R protein levels in BV2 cells.

Conclusion

Nicotine may increase pain hypersensitivity by promoting the expression of P2X4R, BDNF, and IL-1β through modulation of IRF8 levels in microglial cells.
Forkhead transcription factor FOXO1 is involved in hypoxia/reoxygenation-induced gonadotropin-releasing hormone decline
Authors: Shi Chun , Li Guihua , Guo Han , Liu Xintong
Published: November 2020

Previously, it has been demonstrated that aging is associated with nuclear factor-κB (NF-κB)-mediated hypothalamic gonadotropin-releasing hormone (GnRH) decrease. The hypothalamus is one of the brain regions that are vulnerable to ischemia-reperfusion injury. However, it is unclear whether ischemia-reperfusion has an influence on the hypothalamic GnRH release. In the current study, GT1-7 cells, which are a cell line of hypothalamic GnRH neurons, were subjected to hypoxia-reoxygenation to mimic ischemia-reperfusion. The effect of hypoxia-reoxygenation on the hypothalamic GnRH release was investigated. It was found that GnRH secretion from GT1-7 cells was decreased under the hypoxia-reoxygenation condition. Mechanistic studies revealed that hypoxia-reoxygenation activated nuclear factor-κB (NF-κB) via the protein kinase B (Akt)/forkhead box protein O1 (FOXO1) pathway, thereby inhibitinggnrh1gene. The results of the current study suggested that hypoxia-reoxygenation injury may facilitate the hypothalamic programming of system aging through impairment of hypothalamic GnRH release.
Ice giant system exploration in the 2020s: an introduction
Authors: Fletcher L. N. , Simon A. A. , Hofstadter M. D. , Arridge C. S. , Cohen Ian J. , Masters A. , Mandt K. , Coustenis A.
Published: November 2020

The international planetary science community met in London in January 2020, united in the goal of realizing the first dedicated robotic mission to the distant ice giants, Uranus and Neptune, as the only major class of solar system planet yet to be comprehensively explored. Ice-giant-sized worlds appear to be a common outcome of the planet formation process, and pose unique and extreme tests to our understanding of exotic water-rich planetary interiors, dynamic and frigid atmospheres, complex magnetospheric configurations, geologically-rich icy satellites (both natural and captured), and delicate planetary rings. This article introduces a special issue on ice giant system exploration at the start of the 2020s. We review the scientific potential and existing mission design concepts for an ambitious international partnership for exploring Uranus and/or Neptune in the coming decades.

This article is part of a discussion meeting issue ‘Future exploration of ice giant systems’.
Symptomatic SARS-CoV-2 re-infection of a health care worker in a Belgian nosocomial outbreak despite primary neutralizing antibody response
Authors: Selhorst Philippe , Van Ierssel Sabrina , Michiels Jo , Mariën Joachim , Bartholomeeusen Koen , Dirinck Eveline , Vandamme Sarah , Jansens Hilde , Ariën Kevin K.
Published: November 2020

Background

It is currently unclear whether SARS-CoV-2 re-infection will remain a rare event, only occurring in individuals who fail to mount an effective immune response, or whether it will occur more frequently when humoral immunity wanes following primary infection.

Methods

A case of re-infection was observed in a Belgian nosocomial outbreak involving 3 patients and 2 health care workers. To distinguish re-infection from persistent infection and detect potential transmission clusters, whole genome sequencing was performed on nasopharyngeal swabs of all individuals including the re-infection case’s first episode. IgA, IgM, and IgG and neutralizing antibody responses were quantified in serum of all individuals, and viral infectiousness was measured in the swabs of the reinfection case.

Results

Re-infection was confirmed in a young, immunocompetent health care worker as viral genomes derived from the first and second episode belonged to different SARS-CoV-2 clades. The symptomatic re-infection occurred after an interval of 185 days, despite the development of an effective humoral immune response following symptomatic primary infection. The second episode, however, was milder and characterized by a fast rise in serum IgG and neutralizing antibodies. Although contact tracing and virus culture remained inconclusive, the health care worker formed a transmission cluster with 3 patients and showed evidence of virus replication but not of neutralizing antibodies in her nasopharyngeal swabs.

Conclusion

If this case is representative of most Covid-19 patients, long-lived protective immunity against SARS-CoV-2 might not be likely.
Variation in Mycobacterium tuberculosis genotype and molecular phenotype influence clinical phenotype of Pulmonary tuberculosis and Tuberculous Meningitis infection in host
Authors: Husain Aliabbas A. , Tikariha Hitesh , Nayak Amit R. , Gupta Umesh D. , Bhullar Shraddha S. , Chandak Nitin C. , Monaghan Tanya M. , Daginawla Hatim F. , Singh Lokendra R. , Purohit Hemant J. , Kashyap Rajpal S.
Published: November 2020

In the present study, we investigated tissue specific colonization and virulence characteristics of two different Mycobacterium tuberculosis (MTB) clinical isolates derived from patients with Pulmonary TB (PTB) and Tuberculous Meningitis (TBM). We retrospectively studied a total of 1458 patients diagnosed with TB between 2003 and 2013. Of these, archived sputum and CSF samples were available for 323 TBM and 157 PTB patients. We selected a total of 10 sputum and CSF isolates from each group for further molecular characterization. Methodologies employed included, Gas chromatographic analyses of Fatty Acid Methyl Esters (GC-FAME) followed by MTB genotyping to assess strain diversity. We further assessed the molecular phenotype of each strain through in-vitro cytokine assays & murine MTB model. Our comparative genomics data illustrated two diverse genotypes belonging to H37RV (PTB) and CCDC5079 linkage (TBM), highlighting major variation in membrane protein composition and enzymes that make different mycolic acids. The differential cytokine response by both the strains & GC-FAME analysis further corroborated this variation in membrane composition. This was in agreement with KasIII enzyme, LppA and desaturase related variation in protein. Both MTB strains in mice showed diverse pathogenesis with CCDC5079 infected mice exhibiting higher dissemination to brain compared to the H37RV strain which developed progressive pulmonary disease. These observations suggest that variation in the MTB membrane composition could play an important role in differential colonization of these strains. The study warrants further investigation of membrane proteins with respect to blood brain barrier invasion and pathogenesis.