bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive Impairment Leads to Increased Feelings of Sexual Obligation Among a National Longitudinal Sample of Sexually Active Adults Aged 62 and Older
Authors: Shen Shannon , Liu Hui
Published: June 2022

Background and Objectives

We work from a gendered life-course perspective to examine the relationship between cognitive impairment and feelings of sexual obligation among U.S. older adults.

Research Design and Methods

Data are drawn from 2 rounds of the National Social Life, Health, and Aging Project (2010/2011 and 2015/2016). The analytic sample includes 575 sexually active respondents aged 62–86 at baseline. Cognitive impairment is measured using a survey-adapted version of the Montreal Cognitive Assessment, with categories of normal, mild cognitive impairment, and dementia. We estimate cross-lagged models to test the potential reciprocal relationships between cognitive impairment and feelings of sexual obligation.

Results

Older adults with dementia at baseline had significantly higher odds of sexual obligation 5 years later than their peers with normal cognition at baseline, after adjusting for gender, race/ethnicity, education, income, age, marital status, self-rated health, depression, comorbidities, and sexual obligation at baseline. We find no evidence of a reciprocal relationship, as sexual obligation at baseline did not predict later cognitive status.

Discussion and Implications

Older adults with dementia often remain sexually active after their 60s, and many of them feel obligated to have sex with their partner. Our study highlights the importance of understanding the context of their sexual lives. The quality of their sexual relationship, such as whether they feel a duty to maintain their earlier sexual activity or please their partner, and the health implications of sexual obligation should be considered alongside the increase of older adults with dementia.
Patterns of Phenotypic Evolution Associated with Marine/Freshwater Transitions in Fishes
Authors: de Brito Victor , Betancur-R Ricardo , Burns Michael D , Buser Thaddaeus J , Conway Kevin W , Fontenelle João Pedro , Kolmann Matthew A , McCraney W Tyler , Thacker Christine E , Bloom Devin D
Published: June 2022

Evolutionary transitions between marine and freshwater ecosystems have occurred repeatedly throughout the phylogenetic history of fishes. The theory of ecological opportunity predicts that lineages that colonize species-poor regions will have greater potential for phenotypic diversification than lineages invading species-rich regions. Thus, transitions between marine and freshwaters may promote phenotypic diversification in trans-marine/freshwater fish clades. We used phylogenetic comparative methods to analyze body size data in nine major fish clades that have crossed the marine/freshwater boundary. We explored how habitat transitions, ecological opportunity, and community interactions influenced patterns of phenotypic diversity. Our analyses indicated that transitions between marine and freshwater habitats did not drive body size evolution, and there are few differences in body size between marine and freshwater lineages. We found that body size disparity in freshwater lineages is not correlated with the number of independent transitions to freshwaters. We found a positive correlation between body size disparity and overall species richness of a given area, and a negative correlation between body size disparity and diversity of closely related species. Our results indicate that the diversity of incumbent freshwater species does not restrict phenotypic diversification, but the diversity of closely related taxa can limit body size diversification. Ecological opportunity arising from colonization of novel habitats does not seem to have a major effect in the trajectory of body size evolution in trans-marine/freshwater clades. Moreover, competition with closely related taxa in freshwaters has a greater effect than competition with distantly related incumbent species.
Bismut–Cheeger Eta Form and Higher Spectral Flow
Authors: Liu Bo
Published: June 2022

We prove the variation formula, the embedding formula, and the adiabatic limit formula for equivariant Bismut–Cheeger eta forms with a fiberwise compact Lie group action. We only need the condition that the kernels of corresponding fiberwise Dirac operators form vector bundles.
News Arrival, Time-Varying Jump Intensity, and Realized Volatility: Conditional Testing Approach
Authors: Erdemlioglu Deniz , Yang Xiye
Published: June 2022

This paper introduces new econometric tests to identify stochastic intensity jumps in high-frequency data. Our approach exploits the behavior of a time-varying stochastic intensity and allows us to assess how intensely stock market reacts to news. We describe the asymptotic properties of our test statistics, derive the associated central limit theorem and show in simulations that the tests have good size and reasonable power in finite-sample cases. Implementing our testing procedures on the S&P 500 exchange-traded fund data, we find strong evidence for the presence of intensity jumps surrounding the scheduled Federal Open Market Committee (FOMC) policy announcements. Intensity jumps occur very frequently, trigger sharp increases in realized volatility and arrive when differences in opinion among market participants are large at times of FOMC press releases. Unlike intensity jumps, volatility jumps fail to explain the variation in news-induced realized volatility.
The relationship between individual and environmental factors related to health, nutritional status, and diet in elderly people living alone in Japan
Authors: Ishikawa Midori , Yokoyama Tetsuji
Published: June 2022

Aging is an essential milestone that governments worldwide must plan for. At a global level, Japan currently has the highest share of population older than 65 years. Thus, the Japanese experience may be a useful guide to other countries as they consider their policies. Elderly individuals living alone encounter many challenges typically not faced by those living in a multiperson household. Nutrition status and diet are 2 such challenges, both of which are crucial determinants of health and well-being. The health and nutrition statuses as well as some other factors in elderly individuals living alone in Japan were investigated. The identification of the factors relating to food diversity, social relationships, and physical ability, among others, indicates, as hypothesized, that the relationship between individual and environmental factors is associated with the health, nutritional statuses, and diets of elderly people living alone. The findings and approach may be useful to scholars and policy makers in significantly aging societies like Japan as well as other societies experiencing population aging.
Supreme Court and the Practice of Oncology
Authors: Chabner Bruce A , Bates Susan E
Published: June 2022

The past and future Editors-in-Chief of The Oncologist offer thoughts on the recent U.S. Supreme Court leak and its significance for other areas of medical practice.
Analysis of the Arabidopsiscoilinmutant reveals a positive role of AtCOILIN in plant immunity
Authors: Abulfaraj Aala A , Alhoraibi Hanna M , Mariappan Kiruthiga , Bigeard Jean , Zhang Huoming , Almeida-Trapp Marilia , Artyukh Olga , Abdulhakim Fatimah , Parween Sabiha , Pflieger Delphine , Blilou Ikram , Hirt Heribert , Rayapuram Naganand
Published: June 2022

Biogenesis of ribonucleoproteins occurs in dynamic subnuclear compartments called Cajal bodies (CBs). COILIN is a critical scaffolding component essential for CB formation, composition, and activity. We recently showed that Arabidopsis (Arabidopsis thaliana) AtCOILIN is phosphorylated in response to bacterial elicitor treatment. Here, we further investigated the role of AtCOILIN in plant innate immunity. Atcoilin mutants are compromised in defense responses to bacterial pathogens. Besides confirming a role of AtCOILIN in alternative splicing (AS), Atcoilin showed differential expression of genes that are distinct from those of AS, including factors involved in RNA biogenesis, metabolism, plant immunity, and phytohormones. Atcoilin mutant plants have reduced levels of defense phytohormones. As expected, the mutant plants were more sensitive to the necrotrophic fungal pathogen Botrytis cinerea. Our findings reveal an important role for AtCOILIN in innate plant immunity.
The dopaminergic system supports flexible and rewarding dyadic motor interactive behaviour in Parkinson’s Disease
Authors: Era Vanessa , Candidi Matteo , Pezzetta Rachele , Pulcini Claudia , D’Antonio Sara , Zabberoni Silvia , Peppe Antonella , Costa Alberto , Taglieri Sara , Carlesimo Giovanni Augusto , Aglioti Salvatore Maria
Published: June 2022

Studies indicate that the dopaminergic system (DAS) supports individual flexible behaviour. While flexibility is quintessential to effective dyadic motor interactions, whether DAS mediates adaptations of one’s own motor behaviour to that of a partner is not known. Here, we asked patients with Parkinson’s Disease (PD) to synchronize their grasping movements with those of a virtual partner in conditions that did (Interactive) or did not (Cued) require to predict and adapt to its actions. PD performed the task during daily antiparkinsonian treatment (‘On’ condition) or after drug-withdrawal (‘Off’ condition). A group of healthy individuals also served as control group. In the Interactive condition, PDs performed better and found the interaction more enjoyable when in ‘On’ than in ‘Off’ condition. Crucially, PD performance in the ‘On’ condition did not differ from that of healthy controls. This pattern of results hints at the key role of the DAS in supporting the flexible adaptation of one’s own actions to the partner’s during motor interactions.
Virtual Pediatric Orthopaedic Fellowship Interviews During the Pandemic: What Did the Applicants and Programs Think?
Authors: Inclan Paul M. , Woiczik Marcella R. , Cummings Jason , Goodwin Ryan , Hosseinzadeh Pooya
Published: June 2022

Background:

The COVID-19 pandemic precluded in-person interviews for the 2020-2021 fellowship application cycle and may impact future interview cycles. No information is available detailing the implications of a virtual format on either the interviewee or the fellowship program.

Methods:

Two surveys regarding the 2020-2021 virtual interview season were developed and distributed by the Pediatric Orthopaedic Society of North America (POSNA) Fellowship Training and Practice Qualifications Committee: one survey for fellowship applicants and one survey for fellowship program directors.

Results:

Surveys were completed by 45 pediatric orthopaedic fellowship applicants and 34 fellowship program directors. Nineteen (42.2%) applicants applied to more programs because of the virtual format and 30 (66.7%) applicants accepted more interviews because of the virtual format. Thirty-one (67%) applicants did not feel the virtual interview format negatively affected their match process. Thirty-eight (84.4%) applicants indicated that they saved >$2000 with the virtual format. Approximately half (22/45, 48.5%) of the applicants would keep the fellowship-interview process virtual—even if in-person interviews were possible—whereas 8 (17.8%) applicants would transition back toward in-person interviews.

Most program directors utilized online interviews for the first time (n=28, 82.3%) during the 2020-2021 application cycle. Programs interviewed more applicants for the 2020-2021 cycle than in the prior 5 years (19.3 vs. 15.7 applicants, P<0.01), with programs interviewing 10.1 applicants per fellowship position. The majority (n=22, 64.7%) of programs utilized Zoom for the interview platform. Program directors indicated that the applicants were either more accomplished (n=14, 41.2%) or similar in accomplishment (n=20, 58.8%) when compared with the applicants from prior years. Half of the program directors (n=17, 50%) surveyed would utilize virtual interviews next year, even if in-person interviews are possible.

Conclusions:

During the 2020-2021 fellowship application process, interviewees applied to and were interviewed at more programs because of the virtual format, while saving >$2000. In a similar manner, fellowship programs were able to interview a greater number of applicants without adversely impacting the applicant quality. Approximately half of the interviewees and program directors would continue to perform virtual interviews, even if in-person interviews are possible.

Level of Evidence:

Level V.
Comparison of Adjacent Segment Degeneration After Minimally Invasive or Open Transforaminal Lumbar Interbody Fusion
Authors: Jia Jun , Chen Cong , Wang Peng , Wang Lianlei , Liu Xinyu
Published: June 2022

Study Design:

This was a retrospective case series.

Objective:

The purpose of this study was to compare radiologic and clinical outcomes in patients with L4–L5 lumbar spinal stenosis (LSS) who had undergone either minimally invasive (MIS-) or open (O-) transforaminal lumbar interbody fusion (TLIF), especially with regard to the development of adjacent segment degeneration (ASDeg).

Summary of Background Data:

ASDeg is defined as the degenerative changes at adjacent segments of a fused segment, with no obvious clinical symptoms.

Materials and Methods:

A total of 121 LSS patients with a minimum 5-year follow-up were included. Patients were divided into 2 groups according to the surgery performed (MIS-TLIF: 57 patients, O-TLIF: 64 patients). Preoperative and final follow-up radiologic parameters were determined. The incidence of ASDeg was evaluated and compared between the 2 groups. Visual Analog Scale score, Japanese Orthopaedic Association score, and Oswestry Disability Index were used to assess clinical outcomes.

Results:

Before surgery, no significant difference was found between MIS-TLIF and O-TLIF groups regarding demographic, radiologic, and clinical data. After a 5-year follow-up, the incidence of ASDeg in LSS patients was 47.1% (57/121). ASDeg was mostly located at the cranial segment of the fused level in each group. The most common type of ASDeg in both groups was intervertebral space collapse. There was a lower chance of ASDeg in MIS-TLIF group than that in O-TLIF group (33.3% vs. 59.4%, P<0.01). Postoperatively, both groups had significant improvement in clinical outcomes, and there were no statistically significant intergroup differences assessed by Visual Analog Scale, Japanese Orthopaedic Association, and Oswestry Disability Index scores.

Conclusion:

The clinical effect of MIS-TLIF and O-TLIF were similar, but the incidence of ASDeg was significantly lower after MIS-TLIF at 5-year follow-up.
Lung Ultrasound to Assist ICU Admission Decision-Making Process of COVID-19 Patients With Acute Respiratory Failure
Authors: Aguersif Amazigh , Sarton Benjamine , Bouharaoua Sihem , Gaillard Lucien , Standarovski Denis , Faucoz Orphée , Martin Blondel Guillaume , Khallel Hatem , Thalamas Claire , Sommet Agnes , Riu Béatrice , Morand Eric , Bataille Benoit , Silva Stein
Published: June 2022

OBJECTIVES:

There is only low-certainty evidence on the use of predictive models to assist COVID-19 patient’s ICU admission decision-making process. Accumulative evidence suggests that lung ultrasound (LUS) assessment of COVID-19 patients allows accurate bedside evaluation of lung integrity, with the added advantage of repeatability, absence of radiation exposure, reduced risk of virus dissemination, and low cost. Our goal is to assess the performance of a quantified indicator resulting from LUS data compared with standard clinical practice model to predict critical respiratory illness in the 24 hours following hospital admission.

DESIGN:

Prospective cohort study.

SETTING:

Critical Care Unit from University Hospital Purpan (Toulouse, France) between July 2020 and March 2021.

PATIENTS:

Adult patients for COVID-19 who were in acute respiratory failure (ARF), defined as blood oxygen saturation as measured by pulse oximetry less than 90% while breathing room air or respiratory rate greater than or equal to 30 breaths/min at hospital admission. Linear multivariate models were used to identify factors associated with critical respiratory illness, defined as death or mild/severe acute respiratory distress syndrome (Pao
2/Fio
2 < 200) in the 24 hours after patient’s hospital admission.

INTERVENTION:

LUS assessment.

MEASUREMENTS AND MAIN RESULTS:

One hundred and forty COVID-19 patients with ARF were studied. This cohort was split into two independent groups: learning sample (first 70 patients) and validation sample (last 70 patients). Interstitial lung water, thickening of the pleural line, and alveolar consolidation detection were strongly associated with patient’s outcome. The LUS model predicted more accurately patient’s outcomes than the standard clinical practice model (DeLong test: Testing: z score = 2.50, p value = 0.01; Validation: z score = 2.11, p value = 0.03).

CONCLUSIONS:

LUS assessment of COVID-19 patients with ARF at hospital admission allows a more accurate prediction of the risk of critical respiratory illness than standard clinical practice. These results hold the promise of improving ICU resource allocation process, particularly in the case of massive influx of patients or limited resources, both now and in future anticipated pandemics.
Sudden deaths due to accidental leakage of Lindane from a storage tank in a village, Sitapur, Uttar Pradesh, India, 2020
Authors: Jain Piyush , Kapoor Amit , Rubeshkumar Polani , Raju Mohankumar , Joseph Bency , Bhat Prashant , Ganeshkumar Parasuraman , Kesavachandran Chandrasekharan Nair , Patel Devendra Kumar , Manickam Natesan , Kaur Prabhdeep
Published: June 2022

Background:

Chemical leakages cause devastating health effects on humans. On 6 February 2020, seven deaths were reported following a hazardous chemical leakage in a village in Uttar Pradesh, India. We investigated the event to identify the cause and propose recommendations.

Methods:

We defined a case as sudden onset of breathlessness, headache, or death in the village, 6–7 February 2020. We conducted a house-to-house case search and calculated attack rate (AR) and case-fatality rate (CFR) by age and gender. We conducted an environmental investigation at the leakage site and sent the chemicals for forensic analysis. We obtained the cause of death through autopsy reports.

Results:

Out of 2,942 residents, we identified 23 cases (AR = 8/1,000) and seven deaths (CFR = 30%). The median age of the case was 42 years (range, 2–64 years). The AR was higher among males (14/1,000 [19/1,402]). All the 23 case-patients who were sleeping at the chemical leakage site or visited to witness the event developed symptoms, and all seven cases who were sleeping within 150 meters of the leakage site died. The environmental investigation revealed leakage of hazardous substances from the storage tank. Toxicology analysis confirmed the leaked chemical as Lindane (gamma-hexachlorocyclohexane), and autopsy reports confirmed the cause of death as asphyxia.

Conclusions:

Asphyxia following the leakage of Lindane from the storage tank possibly led to sudden deaths. We recommend using leak-proof tanks to ensure safe storage and disposal, law enforcement, and regulations to prevent people from staying close to chemical storage sites.
Flanged iris hook for capsular bag stabilization
Authors: Soyler Mehmet , Sabur Huri , Unsal Ugur
Published: June 2022

A new surgical technique was demonstrated for fixating the capsular bag to the sclera using a capsular tension segment (CTS) and a flanged iris hook. In a patient with a 180-degree zonular dialysis, a capsular tension ring was implanted into the capsular bag, and a CTS was placed into the zonular dialysis area after cataract removal. Then, an iris hook was directed to the anterior chamber through a side port opposite the zonular dialysis area. After the hook tip was placed into the eyelet of the CTS, a 30-gauge injector was used to guide the hook tip out. Tension was adjusted to ensure the capsular centralization, and a flange was created using cautery. Finally, the procedure was completed by embedding the flange into the sclera. This method is simple, minimally invasive, and time-saving by eliminating the scleral suturing, scleral flaps, or large conjunctival dissections.
Metabolic evaluation: is there really a future?
Authors: Traxer Olivier , Corrales Mariela , Sierra Alba
Published: June 2022

Purpose of review

To confirm the need for a metabolic evaluation in stone formers based on the latest information published in the last 24 months and in the current 2022 American and European urological guidelines.

Recent findings

Recent studies suggest that urolithiasis prevalence has been increasing since 1990. Along with it, metabolic abnormalities that contribute to the development of kidney stones are also increasing, such as hyperuricosuria, hyperoxaluria, hypocitraturia, hypomagnesuria, hypocalciuria, hypophosphaturia, and hyperuricemia. Those abnormalities can only be detected through a metabolic evaluation in patients with stone disease.

It is important for us, urologists, to have in mind the actual stone prevalence worldwide. As part of our initial evaluation of the patient with urolithiasis, we must not forget to perform the basic metabolic analysis and, according to the patient's risk classification, continue with a deep metabolic analysis. This extensive analysis includes blood and urine tests. The urinalysis covers 24-h urinalysis, and it would be accurate to also have an early fresh urine analysis. Moreover, identifying the stone type is intimately correlated with the search for other metabolic parameters.
The First Successful Combined Full Face and Bilateral Hand Transplant
Authors: Ramly Elie P. , Alfonso Allyson R. , Berman Zoe P. , Diep Gustave K. , Bass Jonathan L. , Catalano Louis W. , Ceradini Daniel J. , Choi Mihye , Cohen Oriana D. , Flores Roberto L. , Golas Alyssa R. , Hacquebord Jacques H. , Levine Jamie P. , Saadeh Pierre B. , Sharma Sheel , Staffenberg David A. , Thanik Vishal D. , Rojas Allison , Bernstein G. Leslie , Gelb Bruce E. , Rodriguez Eduardo D.
Published: June 2022

Background:

Vascularized composite allotransplantation has redefined the frontiers of plastic and reconstructive surgery. At the cutting edge of this evolving paradigm, the authors present the first successful combined full face and bilateral hand transplant.

Methods:

A 21-year-old man presented for evaluation with sequelae of an 80 percent total body surface area burn injury sustained after a motor vehicle accident. The injury included full face and bilateral upper extremity composite tissue defects, resulting in reduced quality of life and loss of independence. Multidisciplinary evaluation confirmed eligibility for combined face and bilateral hand transplantation. The operative approach was validated through 11 cadaveric rehearsals utilizing computerized surgical planning. Institutional review board and organ procurement organization approvals were obtained. The recipient, his caregiver, and the donor family consented to the procedure.

Results:

Combined full face (i.e., eyelids, ears, nose, lips, and skeletal subunits) and bilateral hand transplantation (i.e., forearm level) was performed over 23 hours on August 12 to 13, 2020. Triple induction and maintenance immunosuppressive therapy and infection prophylaxis were administered. Plasmapheresis was necessary postoperatively. Minor revisions were performed over seven subsequent operations, including five left upper extremity, seven right upper extremity, and seven facial secondary procedures. At 8 months, the patient was approaching functional independence and remained free of acute rejection. He had significantly improved range of motion, motor power, and sensation of the face and hand allografts.

Conclusions:

Combined face and bilateral hand transplantation is feasible. This was the most comprehensive vascularized composite allotransplantation procedure successfully performed to date, marking a new milestone in plastic and reconstructive surgery for patients with otherwise irremediable injuries.
Medical Students' Learning Process During Simulated Patient Consultations in Psychiatry: A Grounded Theory Study
Authors: Piot Marie-Aude , Pham-Scottez Alexandra , Bazziconi Pierre-François , Lebailly Thibaut , Le Moal Valérie , Kalindjian Nina , Sulimovic Leslie , Duriez Philibert , Lombardi Laura , Barbotin Bénédicte , Vinckier Fabien , Burn Carine Layat , Rethans Jan-Joost , Tesnière Antoine , Falissard Bruno
Published: June 2022

Introduction

Recent changes in psychiatric care and teaching, which limit patient contact for medical students, can be partially overcome by simulation-based education in psychiatry. The authors explored the learning processes of medical students during meetings with simulated patients to inform efforts to improve this teaching.

Methods

After recruiting 81 undergraduate medical students from 3 universities to participate in 6 simulation sessions in psychiatry, the authors purposively sampled 21 students to participate in face-to-face individual semistructured interviews analyzed with constructivist grounded theory. Integration of this analysis with those of the simulation consultation videotapes and the debriefing audiotapes improved the triangulation process.

Results

Three organizational themes were identified: developing and structuring representations of psychiatry; integrating subjectivity into learning; and refining and developing psychiatric praxis. Given the broad and in-depth learning that occurs, simulation in psychiatry should respect content validity of SP portrayals to ensure appropriate learning. However, psychological fidelity seems to provide adequate realism while retaining feasibility. Psychiatric simulation also requires the encouragement of student self-confidence and well-being. Within a reflective framework, simulation triggers cognitive reframing, which can alleviate fears and prejudice toward people with mental disorders.

Conclusions

The holistic interactive learning process involved in simulation can address the complexity of the personal and interpersonal features needed in psychiatry.
Secondary Prophylaxis With Inhaled Colistin to Prevent Recurrence of Pseudomonas aeruginosa and Extended-spectrum β-lactamase-producing Enterobacterales Pneumonia in ICU After Lung Transplantation: A Before-and-after Retrospective Cohort Analysis
Authors: Tran-Dinh Alexy , Slassi Lina , De Tymowski Christian , Assadi Maksud , Tanaka Sébastien , Zappella Nathalie , Lortat Jacob Brice , Jean-Baptiste Sylvain , Atchade Enora , Castier Yves , Mal Hervé , Mordant Pierre , Armand-Lefèvre Laurence , Messika Jonathan , Grall Nathalie , Montravers Philippe
Published: June 2022

Background.

Early pneumonia is an independent risk factor for 1-y mortality after lung transplantation (LTx). Pseudomonas aeruginosa is the most common isolate in early pneumonia and is also associated with an increased risk of chronic lung allograft dysfunction. The aim of our study was to evaluate the efficacy of secondary prophylaxis with inhaled colistin (IC) in preventing the recurrence of P aeruginosa or extended-spectrum β-lactamase-producing Enterobacterales (ESBL-PE) pneumonia in the postoperative period in the intensive care unit after LTx.

Methods.

We conducted a before-and-after retrospective cohort study by including all patients who underwent LTx between January 2015 and December 2020 in our center. Secondary prophylaxis with IC was instituted in January 2018 (observation period from January 2015 to December 2017, intervention period from January 2018 to December 2020).

Results.

A total of 271 lung transplants were included (125 in the observation period and 146 in the intervention period). The patients were predominately male (64.2%) with a median age of 57 y and received double LTx (67.9%) for chronic obstructive pulmonary disease/emphysema (36.2%) or interstitial lung disease (48.3%). The proportion of patients who experienced at least 1 recurrence of P aeruginosa or ESBL-PE pneumonia was significantly lower in the intervention period than in the observation period (0.7% versus 7.2%, P = 0.007).

Conclusions.

Our study suggests a potential benefit of secondary prophylaxis with IC to prevent the recurrence of P aeruginosa or ESBL-PE pneumonia in the intensive care unit after LTx.
Progression in multiple sclerosis – a long-term problem
Authors: Bittner Stefan , Zipp Frauke
Published: June 2022

Purpose of review

Disability progression in multiple sclerosis (MS) is strongly linked to central nervous system (CNS)-specific pathological processes that occur throughout all disease stages, but that become clinically evident in later phases of the disease. We here discuss current views and concepts for targeting progressive MS.

Recent findings

Detailed clinical assessment of MS patients has identified an even closer entanglement of relapse-remitting and progressive disease, leading to novel concepts such as ‘progression independent of relapse activity’. Evolving clinical concepts together with a focus on molecular (neurofilament light chain) and imaging (paramagnetic rim lesions) biomarkers might specifically identify patients at risk of developing progressive MS considerably earlier than before. A multitude of novel treatment approaches focus either on direct neuroaxonal protection or myelin regeneration or on beneficially modulating CNS-intrinsic or innate immune inflammation. Although some long-awaited trials have recently been unsuccessful, important lessons could still be drawn from novel trial designs providing frameworks for future clinical studies.

Targeting progressive disease biology and repairing established damage is the current central challenge in the field of MS. Especially, the compartmentalized adaptive and innate CNS inflammation is an attractive target for novel approaches, probably as a combinatory approach together with neuroprotective or myelin regenerating strategies.
Microglia in multiple sclerosis – pathogenesis and imaging
Authors: Airas Laura , Yong V. Wee
Published: June 2022

Purpose of review

Microglia normally protects the central nervous system (CNS) against insults. However, their persistent activation in multiple sclerosis (MS) contributes to injury. Here, we review microglia activation in MS and their detection using positron emission tomography (PET).

Recent findings

During lesion evolution and the progression of MS, microglia activity may contribute to neurotoxicity through the release of pro-inflammatory cytokines, reactive oxidative species, proteases and glutamate. A means to detect and monitor microglia activation in individuals living with MS is provided by positron emission tomography (PET) imaging using the mitochondrial 18-kDa translocator protein (TSPO) ligand. TSPO PET imaging shows increased microglial activation within the normal appearing white matter that precedes radiological signs of neurodegeneration measured by T2 lesion enlargement. PET-detected microglia activation increases with progression of MS. These findings demand the use of CNS penetrant inhibitors that affect microglia. Such therapies may include hydroxychloroquine that is recently reported in a small study to reduce the expected progression in primary progressive MS, and Bruton's tyrosine kinase inhibitors for which there are now eleven Phase 3 registered trials in MS.

Microglial activation drives injury in MS. PET imaging with microglia-specific ligands offer new insights into progression of MS and as a monitor for treatment responses.
Pathomechanisms in demyelination and astrocytopathy: autoantibodies to AQP4, MOG, GFAP, GRP78 and beyond
Authors: Mader Simone , Kümpfel Tania , Meinl Edgar
Published: June 2022

Purpose of review

The purpose of this review is to highlight the recently emerging pathomechanisms of diseases associated with autoantibodies to AQP4, MOG, GFAP, GRP78 and further novel targets. We discuss novel biomarkers and therapeutic approaches.

Recent findings

Although complement-mediated cytotoxicity (CDC) is regarded as the major effector mechanism for AQP4-IgG in neuromyelitis optica spectrum disorders (NMOSD), recent studies helped to understand the relevance of complement-independent effector mechanisms. For MOG-IgG mediated diseases the role of CDC is less clear. MOG-IgG may trigger a tightly controlled FcR and BTK-driven microglia proliferative response in MOG-antibody-associated diseases. Differences of antibody-mediated tissue damage may reflect differential response to therapy. In addition, antibodies to GFAP, GRP78 and further novel targets have been implicated in demyelination and astrocytopathy.

Elucidating the whole spectrum of effector functions in diseases mediated by AQP4-IgG and MOG-IgG and understanding the role of additional novel autoantibodies involved in demyelination and astrocytopathy may guide further novel treatment decisions.
Interrogating large multiple sclerosis registries and databases: what information can be gained?
Authors: Trojano Maria , Kalincik Tomas , Iaffaldano Pietro , Amato Maria P.
Published: June 2022

Purpose of review

Although substantial progress has been made in understanding the natural history of multiple sclerosis (MS) and the development of new therapies, many questions concerning disease behavior and therapeutics remain to be answered. Data generated from real-world observational studies, based on large MS registries and databases and analyzed with advanced statistical methods, are offering the scientific community answers to some of these questions that are otherwise difficult or impossible to address. This review focuses on observational studies published in the last 2 years designed to compare the effectiveness of escalation vs. induction treatment strategies, to assess the effectiveness of treatment in pediatric-onset and late-onset MS, and to identify the clinical phenotype of secondary progressive (SP)MS.

Recent findings

The main findings originating from real-world studies suggest that MS patients who will qualify for high-efficacy disease-modifying therapies (DMTs) should be offered these as early as possible to prevent irreversible accumulation of neurological disability. Especially pediatric patients derive substantial benefits from early treatment. In patients with late-onset MS, sustained exposure to DMTs may result in more favorable outcomes. Data-driven definitions are more accurate in defining transition to SPMS than diagnosis based solely on neurologists’ judgment.

Patients, physicians, industry, and policy-makers have all benefited from real-world evidence based on registry data, in answering questions of diagnostics, choice of treatment, and timing of treatment decisions.
New drugs for multiple sclerosis: new treatment algorithms
Authors: Cree Bruce A.C. , Hartung Hans-Peter , Barnett Michael
Published: June 2022

Purpose of review

To discuss recent changes in the multiple sclerosis (MS) treatment algorithm and to present therapies currently in MS clinical trials.

Recent findings

High efficacy disease modifying therapies are optimally beneficial when used in the early, inflammatory phase of MS. Bruton's tyrosine kinase has emerged as an important therapeutic target for both relapsing and progressive forms of MS. Multiple therapies targeting remyelination failed to provide conclusive evidence of broad therapeutic benefit; however, more targeted approaches offer hope that myelin repair might be achieved resulting in specific clinical improvements. Strategies targeting chronic Epstein–Barr virus infection and dysbiosis of the gut microbiome are the first to link microbial risk factors for MS and therapeutic interventions.

A striking number of diverse treatments under investigation bodes well for development of better and more effective therapies in MS.
Return-to-work interventions for persons/employees with mental illnesses
Authors: Hamann Johannes , Lang Anne , Riedl Lina , Brieger Peter
Published: June 2022

Purpose of review

Mental illnesses are among the most common diseases worldwide. Cases of inability to work caused by mental illness are frequent and the related economic burden is immense. A successful reintegration into their work environment of those patients who were on sick leave due to a mental illness is an important prognostic factor for the further course of the disease and helps reducing financial consequences. It was the aim of the present review to give an overview of the status quo of return-to-work interventions in the international literature.

Recent findings

Main themes of interventions addressing return to work of persons with mental illnesses are the provision of psychotherapeutic support with or without combining these approaches with work directed interventions. Personal contact of employees, mental healthcare staff and supervisors may be helpful with regard to facilitating return to work.

Current return to work interventions are mostly elaborate, extensive and expensive without convincing results regarding work related outcome parameters. A variety of reasons might be responsible for this finding, including heterogeneity of outcomes, a poor definition of return-to-work-interventions and the complexity of the issue (involving multiple stakeholders).
Telemedicine in the treatment of addictions
Authors: Caballeria Elsa , López-Pelayo Hugo , Matrai Silvia , Gual Antoni
Published: June 2022

Purpose of review

The purpose of this update is to provide an overview of recent research publications (January 2020–January 2022) on real-time telemedicine solutions for the management of addictions (alcohol, tobacco, opioids, and other drugs).

Recent findings

Motivational interviewing by real-time telemedicine showed effectiveness in youth and adults for risky alcohol use and alcohol use disorders, even when a concurrent mental health disorder exists. Live telemedicine is well accepted for managing tobacco use disorders. The range of interventions for treating opioid use disorder by real-time telemedicine is large and has been increased due to the coronavirus disease 2019 (COVID-19) pandemic (prescription of opioid agonists, peer-to-peer support, counseling, and group therapy).

The COVID-19 pandemic has accelerated the implementation of real-time telemedicine and, in parallel, research has been conducted to test its effectiveness. Videoconferencing and telephone interventions are supported by solid evidence for risky alcohol use and alcohol use disorder, tobacco use disorder and opioid use disorder. The Integration of other types of telemedicine (asynchronous telemedicine and remote monitoring) and with the entire health system is lacking. Many areas and vulnerable populations (e.g., homeless, elderly, and cannabis use disorders) need more attention.
Analysis of outer hair cell electromechanics reveals power delivery at the upper-frequency limits of hearing
Authors: Rabbitt Richard D.
Published: June 2022

Outer hair cells are the cellular motors in the mammalian inner ear responsible for sensitive high-frequency hearing. Motor function over the frequency range of human hearing requires expression of the protein prestin in the OHC lateral membrane, which imparts piezoelectric properties to the cell membrane. In the present report, electrical power consumption and mechanical power output of the OHC membrane–motor complex are determined using previously published voltage-clamp data from isolated OHCs and membrane patches. Results reveal that power output peaks at a best frequency much higher than implied by the low-pass character of nonlinear capacitance, and much higher than the whole-cell resistive–capacitive corner frequency. High frequency power output is enabled by a −90° shift in the phase of electrical charge displacement in the membrane, manifested electrically as emergence of imaginary-valued nonlinear capacitance.
Evaluation of antioxidant and cytotoxic properties of phenolic
N
-acylhydrazones: structure–activity relationship
Authors: Branković Jovica , Milivojević Nevena , Milovanović Vesna , Simijonović Dušica , Petrović Zorica D. , Marković Zoran , Šeklić Dragana S. , Živanović Marko N. , Vukić Milena D. , Petrović Vladimir P.
Published: June 2022

Cancer is still a relentless public health issue. Particularly, colorectal cancer is the third most prevalent cancer in men and the second in women. Moreover, cancer development and growth are associated with various cell disorders, such as oxidative stress and inflammation. The quest for efficient therapeutics is a challenging task, especially when it comes to achieving both cytotoxicity and selectivity. Herein, five series of phenolic
N
-acylhydrazones were synthesized and evaluated for their antioxidant potency, as well as their influence on HCT-116 and MRC-5 cells viability. Among 40 examined analogues, 20 of them expressed antioxidant activity against the DPPH radical. Furthermore, density functional theory was employed to estimate the antioxidant potency of the selected analogues from the thermodynamical aspect, as well as the preferable free-radical scavenging pathway. Cytotoxicity assay exposed enhanced selectivity of a number of analogues toward cancer cells. The structure–activity analysis revealed the impact of the type and position of the functional groups on both cell viability and selectivity toward cancer cells.
Analytic formulation of elastic field around edge dislocation adjacent to slanted free surface
Authors: Shima Hiroyuki , Umeno Yoshitaka , Sumigawa Takashi
Published: June 2022

Explicit and tractable formulation of the internal stress field around edge dislocations is indispensable for considering the mechanics of fine crystalline solids, because the motion of edge dislocations in a slanted direction with respect to the free surface often plays a vital role in the plastic deformation of the solids under loading. In this study, we formulated an analytical solution for the stress distribution that occurs around edge dislocations embedded in a semi-infinite elastic medium. This formulation is based on the image force method and the Airy stress function method; it describes the variation in the stress distribution with changes in the slanted angle between the traction-free flat surface of the medium and the Burgers vector of the edge dislocation. Furthermore, our analytical solution shows that the attractive force acting on the edge dislocation due to the presence of the free surface is always perpendicular to the surface, regardless of the relative angle of the Burgers vector with the surface.
Flexible growth and body mass predict physiological condition at fledging in the synchronously breeding European starling,
Sturnus vulgaris
Authors: Allen Joshua M. , Hodinka Brett L. , Hall Hannah M. , Leonard Kathryn M. , Williams Tony D.
Published: June 2022

Recent studies have reported beneficial carryover effects of juvenile development that predict interspecific survival differences at independence. Yet, traits relating to body size (i.e. morphological traits) have proven to be unreliable predictors of juvenile survival within species. Exploring individual variation of growth trajectories and how they covary with physiology could reveal species-specific developmental modes which have implications for our assessments of juvenile quality. Here, we investigated morphological development of European starlings (
Sturnus vulgaris
) approaching fledging in relation to three components of physiological condition at independence: aerobic capacity, energy state and oxidative status. We found evidence of flexible mass and wing growth which independently covaried with fledgling energy state and aerobic capacity, respectively. By comparison, tarsus and wing length at fledging were unrelated to any physiological trait, while mass was positively associated with principal component scores that comprised aerobic capacity and energy state. Thus, flexible growth trajectories were consistent with ‘developmental plasticity’: adaptive pre-fledging mass recession and compensatory wing growth, which seemingly came at a physiological cost, while fledgling body mass positively reflected overall physiological condition. This highlights how patterns of growth and absolute size may differently reflect fledgling physiology, potentially leading to variable relationships between morphological traits and juvenile fitness.
A global molecular phylogeny yields insights into the dispersal and invasion history ofJunonia, a butterfly genus with remarkable dispersal abilities
Authors: Lalonde Melanie M. L. , Marcus Jeffrey M.
Published: June 2022

The nymphalid butterfly genusJunoniahas remarkable dispersal abilities. Occurring on every continent except Europe and Antarctica,Junoniaare often among the only butterflies on remote oceanic islands. The biogeography ofJunoniahas been controversial, plagued by taxonomic disputes, small phylogenetic datasets, incomplete taxon sampling, and shared interspecific mitochondrial haplotypes.Junoniaoriginated in Africa but its route into the New World remains unknown. Presented here is, to our knowledge, the most comprehensiveJunoniaphylogeny to date, using full mitogenomes and nuclear ribosomal RNA repeats from 40 of 47 described species.Junoniais monophyletic and the genusSalamisis its probable sister clade. Genetic exchange between Indo-PacificJunonia villidaand New WorldJunonia vestinais evident, suggesting a trans-Pacific route into the New World. However, in both phylogenies, the sister clades to most New WorldJunoniacontain both African and Asian species. Multiple trans-Atlantic or trans-Pacificinvasions could have contributed to New World diversification. Hybridization and lateral transfer of mitogenomes, already well-documented in New WorldJunonia, also occurs in at least two Old World lineages (Junonia orithya/Junonia hiertaandJunonia iphita/Junonia hedonia). Variation associated with reticulate evolution creates challenges for phylogenetic reconstruction, but also may have contributed to patterns of speciation and diversification in this genus.
Genetic and genomic architecture of species-specific cuticular hydrocarbon variation in parasitoid wasps
Authors: Buellesbach Jan , Holze Henrietta , Schrader Lukas , Liebig Jürgen , Schmitt Thomas , Gadau Juergen , Niehuis Oliver
Published: June 2022

Cuticular hydrocarbons (CHCs) serve two fundamental functions in insects: protection against desiccation and chemical signalling. How the interaction of genes shapes CHC profiles, which are essential for insect survival, adaptation and reproductive success, is still poorly understood. Here we investigate the genetic and genomic basis of CHC biosynthesis and variation in parasitoid wasps of the genus
Nasonia
. We mapped 91 quantitative trait loci (QTL) explaining the variation of a total of 43 CHCs in F
2
hybrid males from interspecific crosses between three
Nasonia
species. To identify candidate genes, we localized orthologues of CHC biosynthesis-related genes in the
Nasonia
genomes. We discovered multiple genomic regions where the location of QTL coincides with the location of CHC biosynthesis-related candidate genes. Most conspicuously, on a region close to the centromere of chromosome 1, multiple CHC biosynthesis-related candidate genes co-localize with several QTL explaining variation in methyl-branched alkanes. The genetic underpinnings behind this compound class are not well understood so far, despite their high potential for encoding chemical information as well as their prevalence in hymenopteran CHC profiles. Our study considerably extends our knowledge on the genetic architecture governing this important compound class, establishing a model for methyl-branched alkane genetics in the Hymenoptera in general.