bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship between SARS-CoV-2 and hearing loss: A mini-review
Authors: Lee Sin Wai , De Chua Kenneth Wei , Yuen Heng-Wai
Published: November 2022

The most reported symptoms of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were initially fever, dry cough, and sore throat. However, as we continue to review the literature, the loss of taste and smell were also added as clinical symptoms of the novel SARS-CoV-2. At present, the effects of SARS-CoV-2 on the auditory system is still not well-understood. This study is mini-review and aims to find out more about the relationship between SARS-CoV-2 and hearing loss through review of the literature. From our findings, hearing loss is the primary otological symptom of SARS-CoV-2, followed by tinnitus and dizziness. In conclusion, SARS-CoV-2 may have an effect on our auditory system, but due to the small sample sizes in the existing literature, further prospective studies are warranted to determine the relationship between the virus and hearing loss.
Blood pressure measurement in the elderly with atrial fibrillation: an observational study comparing different noninvasive sphygmomanometers
Authors: Mai Shaojun , Zhu Hailan , Li Meijun , Zeng Yanfang , Zhang Yang , Huo Yanchang , Pan Xiong-Fei , Huang Yuli
Published: November 2022

Background:

Atrial fibrillation (AF) has affected millions of adults in the world. It is important to monitor and manage blood pressure (BP) in AF patients. The accuracy of BP monitoring in AF patients with noninvasive methods remains questionable, however.

Objectives:

To compare the accuracy of different noninvasive BP devices (oscillographic sphygmomanometer and pulse wave device) for BP measurement in elderly patients with AF, with a mercury sphygmomanometer as a reference.

Design:

This study was an observational study.

Methods:

Patients with AF from the inpatient department of cardiology were included from 1 January to 31 December 2020. BP measurements were performed by two trained nurses using a tee junction connection on the cuff to connect three sphygmomanometers. The Bland–Altman plot analysis was conducted to compare the agreement of BP measurements. We also compared the agreement of BP measurements through metrics such as accuracy, bias, and precision.

Results:

A total of 202 patients (54.5% female) were included. The Bland–Altman plot analysis showed that the lower and upper limits of agreement (LoAs) of pulse wave/reference were similar to the predefined acceptable clinical limits (10/5 mmHg). The bias and precision in both systolic and diastolic BP were significantly less in pulse wave/reference (a bias of 1.8 and 0.77 mmHg and a precision of 5.20 and 4.66 mmHg, respectively), with corresponding higher accuracy readings (98.51% for P10 in systolic BP and 85.64% for P5 in diastolic BP).

Conclusion:

A novel noninvasive sphygmomanometer – pulse wave device has a good concordance with a mercury sphygmomanometer in BP monitoring, and may be applicable to perform BP measurements in the elderly with AF.
Reducing the return of avoidance and fear by directly targeting avoidance: Comparing incentive-based and instructed extinction of avoidance to passive fear extinction
Authors: Pittig Andre , Wong Alex H. K.
Published: November 2022

Enhancing the reduction of avoidance may optimize treatment for anxiety disorders. Past research focused on boosting fear extinction to reduce avoidance, however, with limited success. Directly extinguishing avoidance may be more promising. This preregistered study tested the impact of incentives and instruction for non-avoidance compared to passive fear extinction on long-term avoidance and fear reduction. On Day 1, participants acquired conditioned fear and avoidance to a conditioned stimulus (CS) paired with an aversive outcome. Next, incentives or instructions encouraged non-avoidance to the CS, which was no longer reinforced by a US regardless of avoidance (Incentives and Instruction group). In a third group, avoidance was unavailable and the CS was passively presented in absence of the US (Passive Fear Extinction group). On Day 2, avoidance retention and reinstatement and return of fear were tested. In the short term, incentives and instruction strongly reduced avoidance with similar fear reduction compared to passive fear extinction. Importantly, incentives and instruction were linked to lower long-term avoidance retention. Avoidance reinstatement was evident in all groups, but avoidance remained higher after passive fear extinction. Finally, incentives yielded a lower return of threat expectancies. Thus, targeting avoidance instead of fear better reduced long-term avoidance and, for incentives, the return of fear. Especially, incentives could be a promising add-on to exposure.
Working dignity into urban geography
Authors: Keegan Caroline
Published: November 2022

This commentary responds to Grossman and Trubina's (2022) article, ‘Dignity in Urban Geography: Starting a Conversation’. I consider their argument and framework for integrating a formal conceptualization of dignity into urban geography research, including the challenges they face in nailing down this slippery, abstract concept, and the many contributions their application presents to the field. In particular, I focus on the relationship between dignity and work – which is notably absent from their discussion but nonetheless presents a productive line of inquiry given the analytical framework they construct.
Poxvirus-driven human diseases and emerging therapeutics
Authors: Srinivasan Rajsri Kritika , Rao Mana
Published: November 2022

Poxviridae have been successful pathogens throughout recorded history, infecting humans among a variety of other hosts. Although eradication of the notorious smallpox has been a globally successful healthcare phenomenon, the recent emergence of Monkeypox virus, also belonging to the Orthopoxvirus genus and causing human disease, albeit milder than smallpox, is a cause of significant public health concern. The ongoing outbreak of monkeypox, demonstrating human–human transmission, in previously nonendemic countries, calls for critical need into further research in the areas of viral biology, ecology, and epidemiology to better understand, prevent and treat human infections. In the wake of these recent events, it becomes important to revisit poxviral infections, their pathogenesis and ability to cause infection across multiple nonhuman hosts and leap to a human host. The poxviruses that cause human diseases include Monkeypox virus, Molluscum contagiosum virus, and Orf virus. In this review, we summarize the current understanding of various poxviruses causing human diseases, provide insights into their replication and pathogenicity, disease progression and symptoms, preventive and treatment options, and their importance in shaping modern medicine through application in gene therapy, oncolytic viral therapies for human cancers, or as poxvirus vectors for vaccines.
Norovirus disease among older adults
Authors: Tsai Helen , Yune Philip , Rao Mana
Published: November 2022

Norovirus, a leading cause of gastroenteritis outbreaks worldwide, results in substantial direct and indirect healthcare costs. Adults older than 65 years of age bear a significant proportion of the disease burden, and the disease course in this population is often more severe and protracted. In this narrative review, we discuss the epidemiology of norovirus infection, mechanisms of pathogenesis, and transmission pertinent to outbreaks along with infection prevention and control efforts. We also describe the clinical manifestations of norovirus disease with a focus on individuals older than 65 years of age, diagnosis and available treatment options, and the challenges and progress within vaccine development.
Acute ECG changes in a woman presenting to coronary care with fluctuating consciousness
Authors: Parker Hannah , El-Medany Ahmed , Crossley Robert
Published: November 2022

Summary

We present the case of a 67-year-old woman brought into the coronary care unit (CCU) with a suspected ST-segment elevation myocardial infarction (STEMI) due to lateral ST-segment elevation on her 12-lead electrocardiogram (ECG) and a significant troponin rise, but no reported chest pain and a fluctuating consciousness level. Whilst in CCU, she deteriorated further with a reduction in consciousness and sluggish pupillary reflexes, warranting urgent computed tomography (CT) of her brain, which confirmed extensive subarachnoid haemorrhage (SAH) with early evidence of hydrocephalus. She was therefore transferred to the local tertiary neurosurgical centre for endovascular coiling. ECG changes alongside a raised troponin are not uncommon findings in SAH and clinicians should exercise vigilance and consider urgent brain imaging in the absence of chest pain and presence of neurological deficit, to prevent adverse events from unnecessary antiplatelet or anticoagulant therapy, and invasive coronary angiography. SAH is a medical emergency and prompt recognition and referral for neurosurgical intervention is integral for optimal patient outcome.
Human-like tele-health robotics for older adults – A preliminary feasibility trial and vision
Authors: Jafari Nooshin , Lim Michael , Hassani Aida , Cordeiro Jennifer , Kam Crystal , Ho Kendall
Published: November 2022

Introduction

The global increase of the aging population presents major challenges to healthcare service delivery. Further, the COVID-19 pandemic exposed older adults’ vulnerability to rapid deterioration of health when deprived of access to care due to the need for social distancing. Robotic technology advancements show promise to improve provision of quality care, support independence for patients and augment the capabilities of clinicians to perform tasks remotely.

Aim

This study explored the feasibility and end-user acceptance of using a novel human-like tele-robotic system with touch feedback to conduct a remote medical examination and deliver safe care.

Method

Testing of a remotely controlled robot was conducted with in-person clinician support to gather ECG readings of 11 healthy participants through a digital medical device. Post-study feedback about the system and the remote examinations conducted was obtained from study participants and study clinicians.

Results

The findings demonstrated the system’s capability to support remote examination of participants, and validated the system’s perceived acceptability by clinicians and end-users who all reported feeling safe interacting with the robot and 72% preferred remote robotic exam over in-person examination.

Conclusion

This paper discusses potential implications of robot-assisted telehealth for patients including older adults who are precluded from having in-person medical visits due to geographic distance or mobility, and proposes next steps for advancing robot-assisted telehealth delivery.
A Smartphone App to Reduce Burnout in the Emergency Department: A Pilot Randomized Controlled Trial
Authors: Monfries Nicholas , Sandhu Naminder , Millar Kelly
Published: November 2022

Background:

Burnout is a significant concern among health care professionals, particularly those working in the emergency department (ED). Given the negative personal and professional consequences that burnout can have on all health care professionals, multidisciplinary solutions are needed to address burnout. Our objective was to evaluate the feasibility and potential impact of resilience training delivered through a smartphone application on burnout among health care professionals working at a tertiary-care pediatric ED.

Methods:

We conducted a single-center pilot randomized controlled study enrolling multidisciplinary health care professionals working in our ED. Participants assigned to the intervention group received self-driven access to a smartphone application that provided a structured resilience curriculum for a period of 3 months. The participants completed psychometric assessments both prior to and following the invention period. Changes in psychometric measures of the intervention group were then compared with a waitlist-control group.

Results:

Following the intervention period, a total of 20 participants were included in the final analysis. The change in participant scores on psychometric measures prior to and following the intervention period was calculated. A statistically significant mean decrease in burnout measure (emotional exhaustion subscale of Maslach-Burnout Inventory mean score −5.88, p < .001) and increase in mindfulness measure (Mindful Attention Awareness Scale mean score 0.51, p < .001) was observed among the intervention group participants.

Conclusions/Application to Practice:

Our study suggests that a resilience training program delivered using a smartphone application can be an effective intervention in reducing burnout and increasing mindfulness skills. Our study also demonstrated the potential feasibility of a randomized controlled study of burnout within a multidisciplinary group of health care professionals.
Thermal transport of biological base fluid with copper and iron oxide nanoparticles in wavy channel
Authors: Guedri Kamel , Abbasi Aamar , Al-Khaled Kamel , Farooq Waseh , Khan Sami Ullah , Khan Muhammad Ijaz , Galal Ahmed M
Published: November 2022

The nanoparticles are frequently used in biomedical science for the treatment of diseases like cancer and these nanoparticles are injected in blood which is transported in the cardiovascular system on the principle of peristalsis. This study elaborates the effects of Lorentz force and joule heating on the peristaltic flow of copper and iron oxide suspended blood based nanofluid in a complex wavy non-uniform curved channel. The Brinkman model is utilized for the temperature dependent viscosity and thermal conductivity. The problem is formulated using the fundamental laws in terms of coupled partial differential equations which are simplified using the creeping flow phenomenon. The graphical results for velocity, temperature, streamlines, and axial pressure are simulated numerically. The concluded observations deduce that the solid volume fraction of nanoparticles reduces the velocity and enhance the pressure gradient and accumulation of trapping bolus in the upper half of the curved channel is noticed for temperature dependent viscosity.
Intersurgeon Consistency of Ulnar Collateral Ligament Repair With Internal Brace: A Biomechanical Analysis
Authors: Kouk Shalen N. , Beason David P. , Rothermich Marcus A. , Dugas Jeffrey R. , Cain E. Lyle
Published: November 2022

Background:

Injury to the ulnar collateral ligament (UCL) of the medial elbow has been treated successfully with ligament repair augmented with internal brace. Previous work has shown that this procedure does not overconstrain the ulnohumeral joint; however, the procedures were conducted by a single surgeon, which controlled for anchor placement and graft tensioning.

Purpose/Hypothesis:

Our purpose was to evaluate the reproducibility of contact mechanics and joint torque after UCL repair with internal brace as performed by different surgeons compared with repair by a single surgeon. It was hypothesized that there would be no significant difference in elbow contact mechanics, valgus torque, or torsional stiffness between the 2 groups.

Study Design:

Controlled laboratory study.

Methods:

Nine pairs of fresh-frozen cadaveric elbows were tested biomechanically under 3 conditions: UCL-intact (UCL-I), UCL-deficient (UCL-D), and UCL-repaired with internal brace augmentation (UCLR-IB). For each pair, 1 elbow was repaired by a single surgeon, and the contralateral elbow was repaired by 1 of 9 other surgeons. Testing consisted of valgus torsion between 0° and 5° with the elbow positioned at 90° of flexion. Ulnohumeral contact mechanics and overall joint torque and stiffness were measured and compared between surgeon groups.

Results:

There were no statistically significant differences between the single-surgeon and multiple-surgeon groups regarding contact area ( P = .83), contact force ( P = .27), peak pressure ( P = .26), or peak force ( P = .30); however, contact pressure was significantly affected ( P = .02) by surgeon group. Compared with UCL-I, both UCL-D and UCLR-IB conditions had a significant overall effect on contact area ( P = .004) and contact force ( P = .05); however, contact pressure ( P = .56), peak pressure ( P = .27), and peak force ( P = .24) were not affected by injury condition. Measurements of elbow torque ( P = .28) and stiffness ( P = .98) were not significantly different between surgeon groups.

Conclusion:

UCL repair with internal brace provided consistent results among several surgeons when compared with a single surgeon. The procedure did not lead to joint overconstraint while also returning the ligament to near-intact levels of resisting valgus stress.

Clinical Relevance:

UCL repair with internal brace augmentation is a reproducible surgical technique that has good clinical outcomes in the literature.
The Politics of School Rezoning in the “Cradle of a Nation”: Racial Segregation, Settler Colonialism, and Private Property in Williamsburg, Virginia
Authors: Mendez Jennifer Bickham , Quark Amy , Aaron Kayla
Published: November 2022

Rezoning public school attendance boundaries offers important possibilities for promoting school integration; however, it tends to generate contentious debates, often with white, middle-class parents furiously opposing school reassignments. In this paper, we ask: what logics and discourses do race and class-privileged parents draw on to justify educational inequities, and how are such discourses employed? To explore these questions we analyze a high school rezoning controversy in the Williamsburg-James City County School Division in Eastern Virginia. We conducted a content analysis of public commentary collected from school board meetings, two district-administered surveys, and social media and local news outlets. We bring together Critical Race and Settler Colonial theoretical perspectives to argue that white, middle-class parents and residents mobilized the intertwined logics of private property and whiteness to claim entitlement to the highly ranked Jamestown High School. They did so by combining well-worn colorblind, deficiency frameworks with argumentative logics that leveraged their position as property owners in affluent neighborhoods. First, they linked home ownership in expensive, residential subdivisions to “responsible parenting,” “freedom,” and “choice.” Second, they constructed the social bonds and “community” forged in overwhelmingly white, high-cost, residential sub-divisions as valuable to schools, making residents deserving of assignment to “the best school.” This analysis sheds crucial light on the discursive linkages between color-blind racism and white private property and how white, class-privileged parents mobilize these deeply intertwined logics to defend entitlement to educational resources.
A Cohort Study of Risk Factors for Failure of Total Ankle Replacements: A Data Linkage Study using the National Joint Registry and NHS Digital
Authors: Jennison Toby , Goldberg Andrew J. , Sharpe Ian T.
Published: November 2022

Category:

Ankle Arthritis

Introduction/Purpose:

Despite the increasing numbers of ankle replacements that are being performed there are still limited studies on the survival of ankle replacements and which factors influence survivorship comparisons between different implants. The primary aim of this study is to link NJR data with NHS digital data to determine the true failure rates of ankle replacements and to determine the risk factors for failure of total ankle replacements

Methods:

A data linkage study combined National Joint Registry Data and NHS Digital data. The primary outcome of failure is defined as the removal or exchange of any components of the implanted device inserted during ankle replacement surgery. Life tables and Kaplan Meier survival charts demonstrated survivorship. Cox proportional hazards regression models with the Breslow method used for ties were fitted to compare failure rates.

Results:

5,562 primary ankle replacement were recorded on the NJR between 1st April 2010 and 31st December 2018. The unadjusted 1-year survivorship of ankle replacements was 98.8% (95% CI 98.4%-99.0the 5-year survival in 2725 patients was 90.2% (95% CI 89.2%-91.1) and the 10-year survival in 199 patients was 86.2% (95% CI 84.6%-87.6%). In univariate cox regression models age, BMI, ASA, Charlson co-morbidity score, indication for surgery were significantly associated with an increased risk of failure. In multivariate cox regression models only age (HR 0.956, 95% CI 0.942-0.970), BMI (HR 1.032, 95% CI 1.006-1.059) and indication (HR 0.880, 95% CI 0.799-0.968) were associated with an increased risk of failure.

Conclusion:

Ankle replacements have been demonstrated to have higher failure rates in younger patients, those with an increased BMI, and those with osteoarthritis. These findings should be taken into account when deciding which patients should undergo an ankle replacement and in counselling them on the likely survivorship of their ankle replacement
Total Talus Replacement: A Systematic Review of the Literature
Authors: Jennison Toby , Dalgleish James S. , Davies Mark , Sharpe Ian T. , Goldberg Andrew J.
Published: November 2022

Category:

Ankle Arthritis

Introduction/Purpose:

Total talus replacements have been proposed as a method to treat talar AVN replacing the entire talus. The potential for total talar replacements has increased with the advent of patient specific implants utilising 3D printing based on CT scanning of the ipsilateral or contralateral talus. The primary aim of this systematic review is to analyse the current literature on total talus replacements. It specifically aims to look at the indications, complications, survival and functional outcomes.

Methods:

A systematic review was undertaken including all levels of evidence and following PRISMA guidelines. Basic percentages and a weighted pooled proportion for failures using the Freeman Tukey double arscine transformation were performed.

Results:

9 papers with 151 patients were included. The mean age ranged from 27.6 to 72, with 5 papers having a mean age of less than 50. Mean follow-up ranged from 12.8 to 58 months. The most common indication was avascular necrosis in 103 patients.4 studies used 3D printing and 5 customised implants. 3 studies undertook a talus replacement with an ankle replacement. 4 studies used ceramic prostheses, 3 cobalt chromium 1 stainless steel and 1 titanium with ceramic surface. Post-operative complications ranged from 0 to 33%. 69.6% of 23 functional outcomes scores demonstrated significant improvement in functional scores with the others demonstrating a non-significant improvement.3 of 151 implants failed requiring further surgery with 2 revisions and 1 amputation. 6 of the 8 studies did not report any operations for failure. The cumulative incidence of failure was 0.1 % (95% CI 0.0- 4.9%).

Conclusion:

Total talus replacements are a potential alternative to tibiotalocalcaneal fusion for patients with avascular necrosis of the talus. Further studies are required to ensure good outcomes prior to an increase in use of this prosthesis.
Predictors of High-Dose Initial Opioid Prescriptions in Primary Osteoarthritis: A Single Institution Analysis
Authors: Johnson Charles , O'Leary Ryan J. , Hoch Caroline P. , Scott Daniel J. , Gross Christopher E.
Published: November 2022

Category:

Ankle Arthritis; Other

Introduction/Purpose:

High-dose opioid prescriptions in osteoarthritis (OA) increase the risk of overdose and chronic opioid dependence, which is associated with worse perioperative outcomes in total joint arthroplasty (TJA). The purpose of this study was to determine the (1) incidence and (2) identify independent risk factors for receiving high-dose initial opioid prescriptions in OA patients.

Methods:

A retrospective chart review was performed to evaluate initial outpatient opioid prescriptions for OA in opioid-naïve adult patients at a single academic institution between 2013 and 2020. Patients with prior surgery or opioid prescriptions were excluded. Patient demographic data, medical comorbidities, Charlson Comorbidity Index (CCI) scores, and prescription metadata were recorded. High-dose prescriptions were defined as daily oral morphine equivalents (OME/d) >=50. Univariate analysis and multivariate logistic regression were used to identify independent predictors for high-risk opioid prescriptions.

Results:

A total of 1,527 patients were identified with an initial opioid prescription for OA, with 21.5% of patients receiving high- dose prescriptions. The majority of high-dose prescriptions (>=50 OME/d) were given oxycodone (56.1%), while low-dose prescriptions (<50 OME/d) were more commonly prescribed hydrocodone-acetaminophen (34.2%) and tramadol (32.5%). Using multivariate logistic regression, patient factors that are independently associated with high-dose prescriptions include decreased age, decreased BMI, white race, and non-orthopaedic encounters. Comorbid factors that were independently predictive of high- dose prescriptions include hip OA, higher CCI scores, and depression. (Table 1)

Conclusion:

Independent predictors for high-dose initial opioid prescriptions in OA include younger age, decreased BMI, white race, non-orthopaedic encounters, hip OA, higher CCI scores, and depression.
Fabrication of micro-hole using novel Maglev EDM
Authors: Sahoo Rajesh , Kumar Deepak , Singh Nirmal Kumar , Bajpai Vivek
Published: November 2022

In the current scenario, micro-manufacturing through the electro-discharge machining (EDM) process is a prominent technique for achieving desired complex micro/nano-features of any product. The precision and accuracy of producing features are the prerequisites of micro-machining. The current work aims to check the feasibility of the novel Maglev EDM for fabricating micro-holes on a thin nickel sheet (thickness = 500 μm). The study presents the viability of the newly developed system by comparing it with the conventional EDM process. A pure direct current power supply is assembled with a magnetic levitation-based gap monitoring mechanism to overcome the setbacks of conventional EDM. The novel setup utilizes the combined effect of the permanent electromagnet to diminish arcing and short-circuiting. The control parameters for the operation were 12 V open-circuit voltage and 2 A peak current while maintaining a duty factor of 95.564 percent. The measured discharge voltage and discharge current were 6.64 V and 900 mA, respectively. Tungsten rod (ø 650 μm) and deionized water were used as a tool and a dielectric medium, respectively, for the experiment. Further, the machined micro-hole and micro-tool analysis have been carried out using high-resolution microscopy, scanning electron microscopy and energy dispersive spectroscopy reports. The newly developed Maglev EDM’s feasibility to produce micro-holes on conductive materials has been confirmed in the present work with an average material removal rate of 40 μg/min.
Papillary Thyroid Cancer Metastases to the Parathyroid Gland
Authors: O’Sullivan Brian , Burton Tom , Ziad Fouzia , Meyer Rochow Goswin
Published: November 2022

Introduction:

Papillary Thyroid cancer (PTC) is the most common malignancy encountered by endocrine surgeons accounting for up to 85% to 90% of all thyroid malignancies. Parathyroid metastases appear to be an uncommon phenomenon however are likely to be underdiagnosed due to routine parathyroid gland preservation during thyroidectomy.

Case:

We present the case of 63-year-old lady with PTC metastases to the parathyroid gland. She underwent total thyroidectomy, central compartment lymph node dissection and selective left neck (levels IIA-IV) lymph node dissection. Final pathology confirmed a 45 mm low grade conventional type papillary carcinoma with microscopic extension into perithyroidal soft tissue focally and into the adjacent left parathyroid gland.

Conclusion:

Parathyroid gland thyroid cancer infiltration/metastasis is rarely reported and likely underdiagnosed. This is the first case of parathyroid gland metastasis reported from New Zealand or Australia to our knowledge. There is currently limited research available to guide whether parathyroid gland infiltration or metastasis is of clinical or prognostic significance and whether a more aggressive treatment strategy is warranted when present.
NRX-0492 degrades wild-type and C481 mutant BTK and demonstrates in vivo activity in CLL patient-derived xenografts
Authors: Zhang Deyi , Harris Hailey M. , Chen Jonathan , Judy Jen , James Gabriella , Kelly Aileen , McIntosh Joel , Tenn-McClellan Austin , Ambing Eileen , Tan Ying Siow , Lu Hao , Gajewski Stefan , Clifton Matthew C. , Yung Stephanie , Robbins Daniel W. , Pirooznia Mehdi , Skånland Sigrid S. , Gaglione Erika , Mhibik Maissa , Underbayev Chingiz , Ahn Inhye E. , Sun Clare , Herman Sarah E. M. , Noviski Mark , Wiestner Adrian
Published: November 2022

Bruton tyrosine kinase (BTK) is essential for B-cell receptor (BCR) signaling, a driver of chronic lymphocytic leukemia (CLL). Covalent inhibitors bind C481 in the active site of BTK and have become a preferred CLL therapy. Disease progression on covalent BTK inhibitors is commonly associated with C481 mutations. Here, we investigated a targeted protein degrader, NRX-0492, that links a noncovalent BTK-binding domain to cereblon, an adaptor protein of the E3 ubiquitin ligase complex. NRX-0492 selectively catalyzes ubiquitylation and proteasomal degradation of BTK. In primary CLL cells, NRX-0492 induced rapid and sustained degradation of both wild-type and C481 mutant BTK at half maximal degradation concentration (DC50) of ≤0.2 nM and DC90 of ≤0.5 nM, respectively. Sustained degrader activity was maintained for at least 24 hours after washout and was equally observed in high-risk (deletion 17p) and standard-risk (deletion 13q only) CLL subtypes. In in vitro testing against treatment-naïve CLL samples, NRX-0492 was as effective as ibrutinib at inhibiting BCR-mediated signaling, transcriptional programs, and chemokine secretion. In patient-derived xenografts, orally administered NRX-0492 induced BTK degradation and inhibited activation and proliferation of CLL cells in blood and spleen and remained efficacious against primary C481S mutant CLL cells collected from a patient progressing on ibrutinib. Oral bioavailability, >90% degradation of BTK at subnanomolar concentrations, and sustained pharmacodynamic effects after drug clearance make this class of targeted protein degraders uniquely suitable for clinical translation, in particular as a strategy to overcome BTK inhibitor resistance. Clinical studies testing this approach have been initiated (NCT04830137, NCT05131022).
Comparison of central venous, oesophageal and mouth occlusion pressure with water-filled catheters for estimating pleural pressure changes in healthy adults
Authors: Flemale A , Gillard C , Dierckx JP
Published: November 2022

The validity of the central venous and water-filled oesophageal catheter technique as a measure of pleural pressure changes was tested in ten healthy subjects in different body positions during inspiratory efforts with occluded airways, by comparing the simultaneous changes in mouth pressure (delta Pm) taken to represent pleural pressure changes, in central venous pressure (delta Pcv) and in oesophageal pressure (delta Poes). delta Pcv/delta Pm values were close to unity in the sitting and left lateral positions, whereas in the supine and right lateral position, substantial deviations from unity were found in some instances. delta Poes/delta Pm values were close to unity in all positions, except some rare instances. No appreciable phase difference between delta Pm/delta Poes and delta Pm/delta Pcv was found when the amplitude ratios were close to unity. We conclude that valid measurements of pleural pressure changes can be obtained in most instances with the central venous and the water-filled oesophageal catheter system according to the occlusion test procedure.
Bronchial cancer and hypereosinophilia
Authors: Remacle P , Bruart J , Henneghien C
Published: November 2022

A 73 yr old man with a marked eosinophilia, associated with generalized bronchial carcinoma was observed. Ten months earlier his blood count was normal. The mechanism of the eosinophilia is discussed.
The effects of one year of nocturnal cuirass-assisted ventilation in chest wall disease
Authors: Kinnear W , Hockley S , Harvey J , Shneerson J
Published: November 2022

The effects of one year of nocturnal cuirass-assisted ventilation using individually designed cuirass respirators have been investigated in twenty-five patients with chest wall disease. After one year, 22 (88%) of the patients were alive. Daytime arterial blood gases had improved. Functional residual capacity (FRC) had increased but there was no significant change in other lung volumes. Maximum inspiratory pressure (MIP) improved in the subjects with a scoliosis but not in those with a thoracoplasty or neuromuscular disease. Maximum expiratory pressure (MEP) was unchanged. Maximum voluntary ventilation (MVV), the ventilatory response to carbon dioxide and six minute walking distance had all increased. There was no improvement in respiratory symptoms, but a decrease in depression scores and in the time taken to complete a trail test. The mean (SD) number of days spent in hospital over the year was 21.5 (15.1) per patient, with patients consulting their general practitioners less frequently than in the year prior to commencing nocturnal cuirass-assisted ventilation. The cost of commencing a patient on domiciliary nocturnal cuirass-assisted ventilation is estimated as 2470 pounds, and of maintaining them at home for one year as 3302 pounds.
Evidence for a dual effect by beta-adrenoceptor antagonists on post-exercise airway calibre
Authors: Berkin KE , Walker G , Thomson NC
Published: November 2022

The effect of selectivity of beta-adrenoceptor antagonists on resting and post-exercise airway calibre in normal subjects was studied. Eight normal subjects were given atenolol 50 mg, propranolol 80 mg and placebo orally, in random order, double-blind. Specific airways conductance and flow-volume curves (partial and complete) were recorded before, 2 hours after drug administration and after exercise. Neither beta-adrenoceptor antagonist had a measurable effect on lung function tests at rest. The post-exercise increase in flow rates measured from partial flow volume curves was inhibited by propranolol but not by the beta-1-selective adrenoceptor antagonist atenolol, whereas both drugs caused a decrease in specific airways conductance after exercise. Beta-adrenoceptor antagonists may have a dual effect on airway calibre. Firstly, a direct effect on the beta-2 receptors in airway smooth muscle may occur. Secondly, beta-adrenoceptor blockade may, in the large airways, inhibit vagal pre-junctional beta-1 receptors which normally inhibit acetylcholine release at the nerve ending, thereby permitting vagally-induced airway narrowing.
Respiratory heat/water loss alone does not determine the severity of exercise-induced asthma
Authors: Noviski N , Bar-Yishay E , Gur I , Godfrey S
Published: November 2022

Respiratory heat loss (RHL) or water loss (RWL) have been proposed as possible triggering factors in exercise and hyperventilation-induced asthma (EIA and HIA). It has recently been demonstrated that exercise intensity and climatic factors are both important in determining the severity of EIA. Eight young asthmatics performed both exercise and isocapnic hyperventilation (IHV) manoeuvres under identical climatic conditions, as part of our investigation of these interactive factors which determine the severity of the asthmatic response. It was found that, when challenged at low ventilatory levels, exercise produced a significantly attenuated asthmatic response compared to IHV. The fall in forced expired volume in 1 sec (delta FEV1) following exercise was 15 +/- 4% as compared with 27 +/- 3% after IHV (p less than 0.002). It is concluded that while the hypernoea in exercise may serve as a trigger, exercise per se introduces an additional factor which serves to limit the full response seen with IHV. This attenuated response is revealed at low ventilatory levels but is masked at high levels.
Reduction in days of illness after long-term treatment with N-acetylcysteine controlled-release tablets in patients with chronic bronchitis
Authors: Rasmussen JB , Glennow C
Published: November 2022

The clinical effect of N-acetylcysteine (NAC) controlled-release tablets, 300 mg b.i.d., and placebo, in chronic bronchitis was investigated. The study was performed as a double-blind six month comparison between active drug and placebo in two parallel groups, with statistical evaluation after four and six months. The patients were chosen from nine centres. One hundred and sixteen out-patients were included and ninety one of them completed the six month study. The acetylcysteine-treated group had a significantly reduced number of sick-leave days caused by exacerbations of chronic bronchitis after the four winter months December-March compared with the control group (NAC 173, placebo 456). The number of exacerbation days was also very much reduced, however, not significantly (NAC 204, placebo 399). At the end of the six month trial, including also two spring months, the absolute numbers of sick-leave days and exacerbation days were still fewer in the acetylcysteine-treated group, (NAC 260, placebo 739) and (NAC 378, placebo 557) respectively. This study demonstrates a significant reduction in sick-leave days after four months of NAC-treatment. A constant tendency to reduction in the number of exacerbations and exacerbation days was also registered after four and six months. The differences in these parameters were, however, not statistically significant. This was probably due to the small number of patients participating.
Water vapour and temperature dynamics in the upper airways of normal and CF subjects
Authors: Primiano FP  , Saidel GM , Montague FW  , Kruse KL , Green CG , Horowitz JG
Published: November 2022

Water vapour partial pressure (PH2O) and temperature (T) were measured together, continuously, at the airway opening (either lips or nares) and at the oropharynx of human subjects with normal lungs or with cystic fibrosis (CF). No apparent differences in PH2O or T were found between normal and CF groups breathing ambient air (22 +/- 2 degrees C). During inspiration the relative humidity at the pharynx for nose breathing (95%) was higher than for mouth breathing (75%). For hot air breathing (48 +/- 2 degrees C), the PH2O and relative humidity of inspired gas at the pharynx was lower for the CF group than for the normal group. Also, the CF group had a higher airway surface temperature at the airway openings on inspiration. These data suggest that when the rate of evaporation is sufficiently high, the rate-limiting step may be water transport through the mucosal tissue and/or secretions. At least for the upper airways, this rate limitation is more evident for CF patients than for normal subjects.
Exercise responses in patients with an enzyme deficiency in the mitochondrial respiratory chain
Authors: Bogaard JM , Busch HF , Scholte HR , Stam H , Versprille A
Published: November 2022

Responses to exercise were obtained in six patients with a biochemically diagnosed enzyme deficiency at the level of NADH-CoQ reductase. The responses were compared with those of a control group, consisting of fourteen patients with inexplicable dyspnoea or muscle pain during exercise, for which no firm diagnosis could be established and of which the exercise responses were in the normal range. Metabolic, ventilatory and cardiological variables such as oxygen uptake (VO2), minute ventilation (VE), respiratory exchange ratio (R), heart rate (HR) and difference in blood lactate or base-excess (BE) between rest and maximal workload were measured during cycle ergometry from samples obtained in the last minutes of four minute periods, in which the load increased stepwise by 30 W per four minutes. The threshold of lactate metabolism (Tlact) was assumed to be equal to the threshold determined both by the VO2 at which the VE versus VO2 response started to deviate from a straight line and the ventilatory equivalent for oxygen (VE/VO2) showed a minimum (Tvent), Tvent was estimated from the mean of these values, obtained by linear and parabolic regression analysis respectively. In the patient group, mean values for symptom limited maximal VO2 (VO2,max,sl; % of VO2,max,ref), Tvent (% of VO2,max,ref) and R at maximal workload were 43, 17 and 1.23 against 85, 47 and 1.06 for the same variables in the control group, respectively. The differences were highly significant (p less than 0.001; p less than 0.005 for mean R difference). Mean maximal HR and mean change in blood lactate or BE were not significantly different in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)
Effects of terbutaline and atenolol on large and small airways in asthmatic patients
Authors: Lammers JW , Muller ME , Folgering HT , van Herwaarden CL
Published: November 2022

In order to localize the main site of action of the beta 2-adrenoceptor selective agonist terbutaline and the beta 1-adrenoceptor selective antagonist atenolol in the airways of asthmatic patients, we compared the effects of these drugs on maximal expiratory flow-volume (MEFV) curves when breathing air and when breathing a helium-oxygen (HeO2) mixture. To investigate whether a shift in localization of the bronchodilator effect occurs when terbutaline is inhaled repeatedly, dose-response curves with terbutaline were performed for parameters derived from MEFV curves when breathing air and for density dependence of expiratory airflow. By measurement of MEFV curves when the patients were breathing air alone, it was not possible to determine whether there is a difference in the bronchoconstrictor effect of atenolol between large and small airways. Inhalation of terbutaline to a cumulative dose of 2.0 mg induced a stepwise improvement in expiratory airflow parameters for large and small airways function when breathing air. Doubling the dose of inhaled terbutaline to 4 mg did not result in any further improvement of lung function. Neither atenolol nor terbutaline induced significant mean changes in density dependence of expiratory airflow. This was partly due to large inter- and intra-individual variations of this parameter. Another possibility is that atenolol and terbutaline effect large and small airways function equally.
Extrinsic allergic alveolitis caused by spores of the oyster mushroom Pleurotus ostreatus
Authors: Cox A , Folgering HT , van Griensven LJ
Published: November 2022

Four mushroom workers have developed an extrinsic allergic alveolitis, after working with the oyster mushroom (Pleurotus ostreatus). After provocation with aerosolized spores under laboratory conditions, the four patients showed the complaints of an extrinsic allergic alveolitis; a rise of body temperature, leucocytosis and changes of lung function parameters were observed. Antibodies against the spores were assessed in the blood of these patients.
Comparison of terbutaline, isotonic saline, ambient air and non-treatment in patients with reversible chronic airway obstruction
Authors: May O , Hansen NC
Published: November 2022

The increase in forced expiratory volume in one second (FEV1) seen in asthmatics after inhalation of isotonic saline was studied in a blind, cross-over investigation of 24 consecutive out-patients presenting with reversible chronic airway obstruction. Forced expiratory manoeuvres allowing the measurement of FEV1 and forced vital capacity (FVC) were performed at six time intervals during a period of one hour according to the following regimes: inhalation of terbutaline by means of a Pari-inhalier Boy for 10 min; inhalation of isotonic saline under the same conditions; inhalation of ambient air under the same conditions (placebo with noisy nebulizer); inhalation of air without the nebulizer (non-treatment) in order to determine whether the impact of treatment by a nebulizer influences the measured lung function. A statistically significant increase in FEV1 was observed after each of the four regimes. The increase was large following terbutaline inhalation. After the other three regimes, it was significantly smaller and of about the same magnitude in each case. The increase in FEV1 after the non-treatment regime was unexpected and could possibly be due to the repeated dynamic spirometry. The increase in FEV1 after isotonic saline and ambient air (noisy nebulizer) did not differ from the increase after the non-treatment regime. We conclude that neither isotonic saline nor the impact of treatment with a noisy nebulizer have a measurable effect on lung function.
Amyloidosis with pleural involvement
Authors: Graham DR , Ahmad D
Published: November 2022

Although amyloidosis of the respiratory tract is well recognized, pleural involvement is very rare with only two cases being reported in the past. We report a case of primary amyloidosis with pleural effusion and suggest that pleural involvement and pleural effusion be added to the classification of pulmonary amyloidosis, and that amyloidosis be added to the list of causes of a pleural effusion.
Variability of the single-breath carbon monoxide transfer factor as a function of inspired oxygen pressure
Authors: Crapo RO , Kanner RE , Jensen RL , Elliott CG
Published: November 2022

We measured single-breath CO transfer factor (TLCO) and alveolar oxygen partial pressure (PAO2) six times at each of three fractions of inspired oxygen (FIO2) (0.17, 0.21, 0.26) in twelve healthy subjects, to determine whether one FIO2 would have the advantage of producing less variable TLCO results than the others. Measured TLCO was adjusted for the increase in carboxyhaemoglobin during the tests. We found no significant differences in intra- or interindividual variance as a function of test FIO2.
Studying the control of breathing in man
Authors: Folgering H
Published: November 2022

The control system of breathing can be considered as a closed-loop system, consisting of two subsystems: the controlling system and the controlled system. Both subsystems are defined by their input-output relationships. In the controlling system the input is the blood gas value; the output is some parameter of ventilation. The controlled system is characterized by an input of ventilation, and an output of blood gas values. In the closed-loop situation the control of breathing can be influenced by outside "disturbances", threatening to disrupt the regulation of the constancy of the internal environment. When studying the control of breathing, and therefore studying the strengths or defects of this homeostatic system, one has to decide whether one intends to investigate the closed-loop or the open-loop situation, and which defect in a subsystem may be the cause of a disrupted homeostasis. What non-feedback stimuli may be active at the moment of the investigation? How can they be kept constant or eliminated? What possible effects from drugs, beverages, nutrients (possibly consumed hours earlier) may still be present? In particular, the output parameters of the controlling system should be carefully chosen to represent that part of the system that one intends to investigate. Disruptions of the control of breathing may have serious consequences for several categories of patients, e.g. those with chronic obstructive pulmonary disease (COPD), asthma, sleep apnoea, sudden infant death syndrome, several neurological syndromes, and the hyperventilation syndrome. Adequate investigation of the control of breathing in these patients is of great importance for their treatment.