bluuebunny/crossref_metadata_2025 huggingface dataset:
P137 Diagnosis of nocturnal hypoventilation in children with neuromuscular disorders by polysomnography – a survey of clinical practice in Australia and New Zealand
Authors: Withers A , Downs J , Wilson A , Hall G
Published: November 2022

Background

Diagnosis of nocturnal hypoventilation requires measurement of pCO2 during sleep, which can occur via exhaled gas (capnography) or transcutaneous methods. Different national and international definitions of hypoventilation exist, which may contribute to significant variation in clinical practice.

Methods

An electronic survey was completed by pediatric sleep physicians in Australia and New Zealand to determine how pCO2 was measured during polysomnography, what pCO2 data was available to reporting physicians/included in the report and which definitions of hypoventilation physicians use.

Results

More than two thirds (70%) of physicians indicated that in their centre pCO2 was collected via transcutaneous measurement only and 30% by both transcutaneous and end-tidal measurement. Twelve definitions of hypoventilation were used, including published definitions from the American Academy of Sleep Medicine manual and the pediatric Australasian Sleep Association/Australasian Sleep Technologists Association recommendations. The most commonly used definition was an increase in pCO2 >50mmHg for >25% total sleep time. The percentage of total sleep time with pCO2 >50mmHg was routinely included in the report and/or easily available in the raw data for 70% of physicians.

Discussion

There was significant variation and lack of standardisation within Australia and New Zealand when measuring and reporting pCO2 during polysomnography as well as definitions of hypoventilation used by pediatric sleep physicians. The Australasian Sleep Association/Australasian Sleep Technologists Association recommendations were not frequently used, possibly due to relevant information not being available to reporting physicians, recommendations being irrelevant and/or outdated and excessive cognitive load associated with remembering multiple definitions.
P140 Non-invasive Ventilation prior to Adenotonsillectomy
Authors: Wood C , Aristobil-Adele S , Wittwer J , Gray K , Waters K
Published: November 2022

Introduction

Prolonged wait times to ENT surgery, combined with the risk for post-operative respiratory events in children with severe OSA led to a clinical pathway of implementing CPAP therapy in children with severe OSA whilst on waiting lists for adenotonsillectomy. This study evaluated the impact of this pathway on the clinical care of these patients.

Methods

A retrospective review of medical records of patients under 18yrs of age diagnosed with OSA and initiated on CPAP whilst awaiting review by ENT / Adenotonsillectomy, between January 2019 and December 2020.

Results

36 patients were identified, age 4.3 ± 3.2 years, 86% male, and 80.6% had comorbidities. 16 (44.4%) were overweight or obese, and for 8 (22.2%) obesity was the primary comorbidity. Mean delays: Sleep study to Referral = 4.5 ± 10.5 weeks, Referral to NIV initiation 5.6 ± 8.7 weeks, and NIV to ENT surgery 13.6 ± 13.6 weeks. Total delay from referral to the surgery was 19.6 ± 19.4 weeks. 31 (86%) children were initiated on therapy in hospital, and five (13.9%) patients were non-compliant with the therapy.

Discussion

Current delays to ENT surgery for children identified with OSA on sleep study average 5 months. Where OSA is sufficient to recommend ENT surgery, the majority (80%) of children tolerated CPAP therapy while they await surgery. We suggest that the benefits obtained are that therapy can be instituted more rapidly than surgery, and where children are able to use CPAP therapy it reduced the requirement for high-dependency or intensive care admission post-operatively.
Betanin ameliorates fipronil-induced nephrotoxicity via activation of Nrf2-HO-1/NQO-1 pathway in albino rat model
Authors: Sakr Samar , Hamed Amira , Atef Mona
Published: November 2022

Fipronil (FPN) is phenylpyrazole insecticide extensively used to control a wide variety of pests. Betanin (BET) is a natural colorant with promising antioxidant and anti-inflammatory effects. This study aimed to investigate the potential protective effect of BET on FPN induced nephrotoxicity in adult male albino rats. Forty rats were assigned into 4 equal groups; Group I (Control); Group II (BET) received 20 mg/kg b.wt/day; Group III (FPN) received 4.8 mg/kg b.wt/day; and Group IV (BET/FPN). All treatments were given orally for 90 days. At the end of experiment, blood samples were collected for analysis of serum urea and creatinine. Kidneys were harvested for determination of kidney injury molecule-1(KIM-1) level; gene expression of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase-1 (NQO-1); oxidative stress biomarkers including malondialdehyde (MDA), protein carbonyl content (PCC), catalase activity (CAT), glutathione peroxidase (GPx), and reduced glutathione (GSH). Histopathological examination and immunohistochemical investigation of Nrf2, nuclear factor kappa B (NF-κB), and caspase-3 were also undertaken. The results revealed kidney dysfunction, downregulation of Nrf2, HO-1, and NQO-1 genes, redox imbalance, structural damage, decreased Nrf2 and increased NF-κB immune-expression, in addition to strong caspase-3 immunoreactivity in FPN-treated group. In the combined group, BET co-administration resulted in functional and structural amelioration, up-regulation of Nrf2, HO-1, and NQO-1 genes, mitigation of redox imbalance, and strong anti-inflammatory and antiapoptotic effects. In conclusion, BET via activation of Nrf2-HO-1/NQO-1 pathway, exhibits beneficial antioxidant, anti-inflammatory, and antiapoptotic effects against FPN-induced nephrotoxicity.
High abscisic acid and low root hydraulic conductivity may explain low leaf hydration in ‘Mandarin’ lime exposed to aluminum
Authors: Silva Giselle Schwab , Gavassi Marina Alves , de Oliveira Carvalho Brenda Mistral , Habermann Gustavo
Published: November 2022

The first symptom of aluminum (Al) toxicity is the inhibition of root growth, which has been associated with low leaf hydration, with negative consequences for leaf gas exchange including stomatal conductance (gs) observed in many plant species. Here we asked whether low leaf hydration occurs before or after the inhibition of root growth of Citrus × limonia Osbeck (‘Mandarin’ lime) cultivated for 60 days in nutrient solution with 0 and 1480 μM Al. The length, diameter, surface area and biomass of roots of plants exposed to Al were lower than control plants only at 30 days after treatments (DAT). Until the end of the study, estimated gs (measured by sap flow techniques) was lower than in control plants from 3 DAT, total plant transpiration (Eplant) and root hydraulic conductivity (Lpr) at 7 DAT, and midday leaf water potential (Ψmd) and relative leaf water content at 15 DAT. Abscisic acid (ABA) in leaves was twofold higher in Al-exposed plants 1 DAT, and in roots a twofold higher peak was observed at 15 DAT. As ABA in leaves approached values of control plants after 15 DAT, we propose that low gs of plants exposed to Al is primarily caused by ABA, and the maintenance of low gs could be ascribed to the low Lpr from 7 DAT until the end of the study. Therefore, the low leaf hydration in ‘Mandarin’ lime exposed to Al does not seem to be caused by root growth inhibition or by a simple consequence of low water uptake due to a stunted root system.
Identification and Observation of Infection Processes of Colletotrichum Species Associated with Persimmon Anthracnose in Guangxi, China
Authors: Zhang Miaomiao , Forte-Perri Vivian , Sun Wenxiu , Tang Lihua , Huang Suiping , Guo Tangxun , Chen Xiaolin , Li Qili
Published: November 2022

Persimmon originated from China where it has a long cultivation history. Anthracnose fruit rot and leaf blight caused by Colletotrichum species are major diseases of persimmon in China and cause severe economic losses. To determine the species causing anthracnose of persimmon in Guilin, Guangxi Province, diseased samples were collected from the four local counties: Gongcheng, Yangshuo, Pingle, and Lipu. Seventy-five isolates were obtained from persimmon samples with anthracnose symptoms and had similar morphological characteristics. Isolates were identified using a BLAST search and phylogenetic analysis of the internal transcribed spacer region, glyceraldehyde-3-phosphate dehydrogenase, partial actin, β-tubulin, chitin synthase genomic regions, Apn2-Mat1-2 intergenic spacer, and the partial mating type gene and calmodulin genes. Five species (C. fructicola, C. horii, C. karstii, C. cliviicola, and C. siamense) accounted for 54.7, 25.3, 12.0, 5.3, and 2.7%, respectively, of the total isolates. All five Colletotrichum species were pathogenic on attached leaves and detached fruits of persimmon (cultivar Gongcheng Yueshi) in pathogenicity assays. The infection processes of the five Colletotrichum species were observed on persimmon leaves using light microscopy. Conidia of C. fructicola germinated at 12 h post inoculation (hpi) and quickly formed acervuli at 6 days post inoculation (dpi) and were the most aggressive. By contrast, conidia of C. cliviicola germinated at 3 hpi but produced the acervuli at 8 dpi and were the least aggressive. This is the first description of C. fructicola, C. cliviicola, and C. siamense as causal agents of persimmon anthracnose in Guangxi Province, China.
Comparative Effectiveness of Manual Therapy Interventions on Pain and Pressure Pain Threshold in Patients With Myofascial Trigger Points
Authors: Guzmán Pavón María J. , Cavero Redondo Iván , Martínez Vizcaíno Vicente , Ferri Morales Asunción , Lorenzo García Patricia , Álvarez Bueno Celia
Published: November 2022

Objectives:

Myofascial trigger points (MTPs) are one of the most important causes of musculoskeletal pain. Evidence has suggested a positive effect of manual therapy in the treatment of MTPs. However, a comprehensive review comparing the effect of different manual therapy techniques are lacking. Thus, we conducted a network meta-analysis of randomized controlled trials to determine the type of manual therapy technique that has the greatest positive influence in patients with MTPs.

Materials and Methods:

PubMed, Web of Science, Cochrane Library, and Scopus databases were searched to identify direct and indirect evidence comparing the effectiveness of different types of manual therapy interventions on pain intensity and pressure pain threshold (PPT) in patients with MTPs. Risk of bias was assessed using the Cochrane RoB2 tool. A pairwise meta-analysis for direct and indirect comparisons between intervention and control/nonintervention groups was carried out.

Results:

A total of 37 studies were eligible for analysis. Combined interventions had the highest effect size for pain (−1.40; 95% CI, −2.34, −0.47), and the highest probability to be the best intervention and the highest Surface Under the Cumulative Ranking (64.7% and 87.9%, respectively). Afferent reduction techniques, understood as the interventions aimed to restore muscle spindles helping to dictate sarcomere length and tone in MTPs, had the highest effect size for PPT (0.93; 95% CI, 0.47, 1.39), and the highest probability to be the best intervention and the highest Surface Under the Cumulative Ranking (34.7% and 71.2%, respectively). The results were consistent in sensitivity analyses, with minimal inconsistencies between direct and indirect results.

Discussion:

Manual therapy interventions should be considered an effective strategy for pain and PPT in patients with MTPs. The results suggest that among the different manual therapy modalities, combined and afferent reduction techniques are the most effective for pain and PPT, respectively.
Long-Term Outcome of Severe Metabolic Acidemia in ICU Patients, a BICAR-ICU Trial Post Hoc Analysis
Authors: Bendiab Eddine , Garnier Fanny , Soler Marion , Fosset Maxime , Jaber Samir , Molinari Nicolas , Jung Boris ,   on behalf of the BICAR-ICU Investigators
Published: November 2022

OBJECTIVES:

Long-term prognosis of ICU survivors is a major issue. Severe acidemia upon ICU admission is associated with very high short-term mortality. Since the long-term prognosis of these patients is unknown, we aimed to determine the long-term health-related quality of life and survival of these patients.

DESIGN:

Post hoc analysis of a multicenter, randomized, controlled trial.

SETTING:

Twenty-six French ICUs.

PATIENTS:

Day 28 critically ill survivors admitted with severe acidemia and enrolled in the BICAR-ICU trial.

INTERVENTION:

Sodium bicarbonate versus no sodium bicarbonate infusion according to the randomization group.

MEASUREMENTS AND MAIN RESULTS:

The primary outcome was health-related quality of life (HRQoL) measured with the 36-item Short Form Health Survey and the EuroQol 5-D questionnaires. Secondary outcomes were mortality, end-stage renal disease treated with renal replacement therapy or renal transplantation, place of residence, professional status, and ICU readmission. HRQoL was reduced with no significant difference between the two groups. HRQoL was reduced particularly in the role-physical health domain (64/100 ± 41 in the control group and 49/100 ± 43 in the bicarbonate group, p = 0.28), but it was conserved in the emotional domains (96/100 ± 19 in the control group and 86/100 ± 34 in the bicarbonate group, p = 0.44). Forty percent of the survivors described moderate to severe problems walking, and half of the survivors described moderate to severe problems dealing with usual activities. Moderate to severe anxiety or depression symptoms were present in one third of the survivors. Compared with the French general population, HRQoL was decreased in the survivors mostly in the physical domains. The 5-year overall survival rate was 30% with no significant difference between groups.

CONCLUSIONS:

Long-term HRQoL was decreased in both the control and the sodium bicarbonate groups of the BICAR-ICU trial and was lower than the general population, especially in the physical domains.
When a Traditional Medicine Customer Becomes a Plastic Surgery Patient
Authors: Mrad Mohamed Amir , Shah Mardan Qutaiba N. M. , Kariri Samah A. , Merdad Khalid A.
Published: November 2022

Traditional medicine therapy is practiced locally in the Middle Eastern communities. The balance between benefit and harm might tip toward the latter if its practice continues unregulated. Herein is a case of a young man who presented to our clinic complaining of keloid scars that developed following a cupping therapy session. He underwent multiple cupping sessions, without prior consent or information regarding potential complications. Finally, we present an algorithm for cupping practitioners to follow to minimize abnormal scarring.
Closing the Gender Gap in Healthcare Leadership: Can Administrative Fellowships Play a Role?
Authors: Robbins Julie , Graham Brooke Z. , Garman Andrew N. , Smith Hall Randa , Simms Jeffrey
Published: November 2022

Goal:

Although women make up most of the healthcare workforce, they are underrepresented in higher levels of leadership positions. Leadership development programs for early careerists, such as administrative fellowships, have been suggested as one strategy for accelerating gender equity in leadership roles. However, the potential impact of these programs has not yet been the subject of systematic evaluation. In this study, we examined the (1) benefits of administrative fellowship programs on career attainment and (2) differences in attainment by gender.

Methods:

We completed this study using a data set involving alumni from a consortium of 11 graduate healthcare management programs whose students frequently pursue administrative fellowships. Our data included individual-level demographic and career attainment data for graduating classes from 5, 10, and 20 years prior to the reference year. Using multiple regression analysis, we tested the relationship of three independent variables—graduation year, gender, and completion of a fellowship—on career attainment. This analysis enabled us to determine differences in overall career attainment by gender, evaluate the role of fellowships in career attainment, and consider the differential impact of fellowships on attainment by gender.

Principal Findings:

Our findings suggest that fellowship programs accelerate leadership career paths for individual leaders, but that the effect is stronger for males than their female counterparts.

Practical Applications:

These findings not only support the value of administrative fellowships for early careerist leadership development but also suggest that closing the gender disparity gap in leadership may require additional and focused career-supportive strategies. We provide recommendations for healthcare organizations in developing their administrative fellowship programs to help minimize the gender disparity in healthcare leadership positions. Furthermore, we discuss research implications and future areas of research in administrative fellowships.
School Hearing Screening With a Portable, Tablet-Based, Noise-Attenuating Audiometric Headset in Rural Nicaragua
Authors: Saunders James E. , Bessen Sarah , Magro Isabelle , Cowan Devin , Gonzalez Quiroz Marvin , Mojica-Alvarez Karen , Penalba Donoso , Reike Catherine , Neimczak Chris , Fellows Abigail , Buckey Jay
Published: November 2022

Objective

To investigate the utility and effectiveness of a noise-attenuating, tablet-based mobile health system combined with asynchronous telehealth evaluations for screening rural Nicaraguan schoolchildren for hearing loss.

Study Design

Prospective population-based survey.

Setting

Rural Nicaraguan communities.

Patients

There were 3,398 school children 7 to 9 years of age.

Intervention(s)

Diagnostic automated and manual audiometry, detailed asynchronous telehealth evaluations

Main Outcome Measure(s)

Referral rates, ambient noise levels, and audiometric results as well as hearing loss prevalence, types, and risk factors.

Results

Despite high ambient noise levels during screening (46.7 dBA), no effect of noise on referral rates on automated audiometry or confirmatory manual audiometry in those who failed automated testing was seen. The overall audiometric referral rate was 2.6%. Idiopathic sensorineural hearing loss (SNHL) and cerumen impaction were the most common types of hearing loss in this population with an estimated prevalence of hearing loss (all types) of 18.3 per 1,000 children. SNHL was associated with both drug exposure during pregnancy (p = 0.04) and pesticide exposure in the home (p = 0.03).

Conclusion

Hearing screening using a tablet-based, noise-attenuating wireless headset audiometer is feasible and effective in rural low-resource environments with moderately elevated ambient noise levels. The referral rate with noise-attenuating headsets was much lower than that previous reports on this population. In addition, manual audiometry resulted in much lower referral rates than automated audiometry. The confirmed hearing loss rate in this study is comparable to reports from other low-income countries that use some form of noise attenuation during screening. Pesticide exposure and drug exposure during pregnancy are potential causes of SNHL in this population.
Trends and Outcomes of Fungal Temporal Bone Osteomyelitis: A Scoping Review
Authors: Macias David , Jeong Seth S. , Van Swol Joshua M. , Moore Jeremy D. , Brennan Emily A. , Raymond Mallory , Nguyen Shaun A. , Rizk Habib G.
Published: November 2022

Introduction

Temporal bone osteomyelitis is an invasive infection most often caused by bacteria and associated with high mortality. Fungal etiologies are rare and little is known of the predictors of disease severity and outcomes in fungal temporal bone osteomyelitis.

Materials and Methods

A scoping review was performed to determine what is known from the literature on how clinical, diagnostic, and treatment characteristics relate to patient outcomes in fungal temporal bone osteomyelitis. Using PRISMA guidelines, three databases were searched to identify all published cases of fungal temporal bone osteomyelitis. Data were extracted from each study, including clinical, diagnostic, and treatment characteristics, and outcomes.

Results

Sixty-eight studies comprising 74 individual cases of fungal temporal bone osteomyelitis were included. All studies were case reports. There were high rates of diabetes, facial nerve palsy, infectious complications, and need for surgical intervention, as well as a significant delay in the evaluation and diagnosis of fungal temporal bone osteomyelitis. Disease recovery was greater in patients presenting with otorrhea, comorbid diabetes, and in those without facial nerve palsy.

Discussion

Many of the defining characteristics of fungal temporal bone osteomyelitis remain unknown, and future reports should focus on determining factors that improve timely diagnosis and treatment of fungal TBO in addition to identifying prognostic indicators for outcomes and survival.
Video Analysis of Otologic Instrument Movement During Resident Mastoidectomies
Authors: Pipaliya Royal M. , Raymond Mallory J. , Rowley M. Andrew , Jasper Polly M. , Meyer Ted A.
Published: November 2022

Objective

To measure surgical instrument movement during resident mastoidectomies and identify metrics that correlate with experience.

Study Design

Retrospective case series.

Setting

Tertiary care center.

Subjects

Ten postgraduate year (PGY) 2, 6 PGY3, 7 PGY4, and 19 PGY5 recordings of mastoidectomy performed by otolaryngology residents.

Interventions

One-minute intraoperative recordings of mastoidectomies performed during cochlear implantation were collected. Drill and suction-irrigator motion were analyzed with sports motion tracking software.

Main Outcome Measures

Mean instrument speed, angle, and angular velocity were calculated. Mann-Whitney U tests compared mean instrument metrics between PGY levels. Change in drill speed for seven residents between their PGY2 to PGY5 years was individually analyzed.

Results

Mean drill speed was significantly greater for PGY5 residents compared with PGY2s (2.9 versus 1.8 cm/s, p = 0.001). Compared with PGY2 residents, suction speed was greater as a PGY5 (1.2 versus 0.9 cm/s; p = 0.201) and significantly greater as a PGY4 (1.5 versus 0.9 cm/s, p = 0.039). Of the seven residents individually analyzed, group mean drill speed increased by 0.4 cm/s, yearly.

Conclusions

Drill and suction-irrigator movement during the second minute of drilling of a cortical mastoidectomy seems to increase with resident level. Objective video analysis is a potential adjunct for differentiating novices from more experienced surgeons and monitoring surgical skills progress.
Hospital-based Health Information Technology Infrastructure
Authors: Chen Jie , Spencer Merianne Rose T. , Buchongo Portia , Wang Min Qi
Published: November 2022

Background:

Alzheimer disease and related dementia (ADRD) is one of the most expensive health conditions in the United States. Understanding the potential cost-savings or cost-enhancements of Health Information Technology (HIT) can help policymakers understand the capacity of HIT investment to promote population health and health equity for patients with ADRD.

Objectives:

This study examined access to hospital-based HIT infrastructure and its association with racial and ethnic disparities in Medicare payments for patients with ADRD.

Research Design:

We used the 2017 Medicare Beneficiary Summary File, inpatient claims, and the American Hospital Association Annual Survey. Our study focused on community-dwelling Medicare fee-for-service beneficiaries who were diagnosed with ADRD. Our study focused on hospital-based telehealth-postdischarge (eg, remote patient monitoring) and telehealth-treatment (eg, psychiatric and addiction treatment) services.

Results:

Results showed that hospital-based telehealth postdischarge services were associated with significantly higher total Medicare payment and acute inpatient Medicare payment per person per year among patients with ADRD on average. The associations between hospital-based telehealth-treatment services and payments were not significant. However, the association varied by patient’s race and ethnicity. The reductions of the payments associated with telehealth postdischarge and treatment services were more pronounced among Black patients with ADRD. Telehealth-treatment services were associated with significant payment reductions among Hispanic patients with ADRD.

Conclusion:

Results showed that having hospital-based telehealth services might be cost-enhancing at the population level but cost-saving for Black and Hispanic patients with ADRD. Results suggested that personalized HIT services might be necessary to reduce the cost associated with ADRD treatment for racial and ethnic minority groups.
A retrospective study of patients treated with by oral anticancer drugs: Impact of pharmacy consultation
Authors: Clou Emmanuelle , Dubois Antonin , Gaudas Julien , Palisson Hugo , Chetouane Kahina , Talarmin Chloé , Meynial Olivia , Nguyen Jacqueline , Assoun Sandra , Benderra Marc-Antoine , Nasrallah Dhekra , Esteso Adoraction , Avenin Danièle , Galula Gilles , Ghebriou Djamel , Gligorov Joseph , Khalil Ahmed , Korenbaum Clément , Prebet Coralie , Foka-Tichoue Hervé , Lotz Jean-Pierre , Debrix Isabelle
Published: November 2022

Introduction:

Pharmacists can contribute to improve prevention and management of patients treated with oral anticancer drugs. The aim of this study was to describe pharmacist interventions in drug-related problems (DRPs), medication optimization, and patient management.

Methods:

The pharmaceutical process allows obtaining exhaustive list of usual patient treatment, patient education, and telephonic follow-up at home. During pharmacy consultation and telephonic follow-up, the number and type of pharmacist interventions were collected and classified into 3 categories: DRPs, medication optimization, and patient management. During telephonic follow-up, pharmacists detected adverse events.

Results:

From February 2016 to May 2020, 224 pharmacy consultations were conducted. A total of 508 pharmacist interventions (248 for pharmacy consultation and 260 for telephonic follow-up) were conducted, with an average of 2.3 pharmacist interventions per patient. Pharmacist interventions were 44.4% for patient management, 29.6% for DRPs, and 26.0% for medication optimization. After pharmacy consultation, 36.2% of patients' usual treatments were amended. Two hundred thirteen adverse events (AEs) were reported, and 38.8% of patients had one or more AEs. AEs detected were 15 for temporary discontinuation of oral anticancer drugs, 25 for emergency consultations, and 3 for hospitalizations.

Conclusion:

Pharmacy consultation has shown that pharmacists can contribute to optimize medicinal care for patients with cancer.
Medical treatments of endometriosis: a review
Authors: Elbasueny Bahi , Geerts Maya , Yang Emily C. , Allaire Catherine , Yong Paul J. , Bedaiwy Mohamed A.
Published: November 2022

Endometriosis is a chronic gynecological disorder that affects approximately 10% of women of reproductive age. Most medical treatments used today for endometriosis pain are hormonal therapies, which are not an option for those trying to conceive and are not tolerated by a subset of patients due to side effects. In this article, we offer a comprehensive review of current and investigational medical therapeutic options used to treat endometriosis pain, as well as a symptom-based systematic approach for patients with painful endometriosis. We have also included recommendations for research to enhance the evolution of novel therapeutic options. A thorough literature search was carried out, and the data were synthesized using a synthesis matrix that classifies and categorizes various arguments.
Does shading on great argus
Argusianus argus
feathers create a three-dimensional illusion?
Authors: Firkins James M. E. , Kelley Laura A.
Published: November 2022

Many animals use shading to infer the three-dimensional (3D) shape of objects, and mimicking natural shading patterns can produce the illusion of 3D form on a flat surface. Over 150 years ago, Charles Darwin noted that the ocelli (eyespots) on the feathers of the great argus
Argusianus argus
, when held vertically during courtship displays to females, were perfectly shaded to resemble 3D hemispheres to human viewers. We tested whether these ocelli appear 3D to birds by training chickens
Gallus gallus domesticus
to select images of either convex or concave shapes using shading cues, and then presenting them with images of great argus ocelli. Chickens successfully learned how to discriminate between convex and concave shapes, and treated the great argus pheasant ocelli in the same way as convex training stimuli. Our findings are consistent with previous studies that birds can perceive 3D shape from shading cues in a similar manner to humans. The perception of great argus ocelli as consistent with 3D shape by avian viewers suggests that shape illusions can play a role in male courtship.
Directional control of neurite outgrowth: emerging technologies for Parkinson's disease using magnetic nanoparticles and magnetic field gradients
Authors: Dhillon K. , Aizel K. , Broomhall T. J. , Secret E. , Goodman T. , Rotherham M. , Telling N. , Siaugue J. M. , Ménager C. , Fresnais J. , Coppey M. , El Haj A. J. , Gates M. A.
Published: November 2022

A challenge in current stem cell therapies for Parkinson's disease (PD) is controlling neuronal outgrowth from the substantia nigra towards the targeted area where connectivity is required in the striatum. Here we present progress towards controlling directional neurite extensions through the application of iron-oxide magnetic nanoparticles (MNPs) labelled neuronal cells combined with a magnetic array generating large spatially variant field gradients (greater than 20 T m
−1
). We investigated the viability of this approach in both two-dimensional and organotypic brain slice models and validated the observed changes in neurite directionality using mathematical models. Results showed that MNP-labelled cells exhibited a shift in directional neurite outgrowth when cultured in a magnetic field gradient, which broadly agreed with mathematical modelling of the magnetic force gradients and predicted MNP force direction. We translated our approach to an
ex vivo
rat brain slice where we observed directional neurite outgrowth of transplanted MNP-labelled cells from the substantia nigra towards the striatum. The improved directionality highlights the viability of this approach as a remote-control methodology for the control and manipulation of cellular growth for regenerative medicine applications. This study presents a new tool to overcome challenges faced in the development of new therapies for PD.
Estimating fine-scale changes in turbulence using the movements of a flapping flier
Authors: Lempidakis Emmanouil , Ross Andrew N. , Quetting Michael , Garde Baptiste , Wikelski Martin , Shepard Emily L. C.
Published: November 2022

All animals that operate within the atmospheric boundary layer need to respond to aerial turbulence. Yet little is known about how flying animals do this because evaluating turbulence at fine scales (tens to approx. 300 m) is exceedingly difficult. Recently, data from animal-borne sensors have been used to assess wind and updraft strength, providing a new possibility for sensing the physical environment. We tested whether highly resolved changes in altitude and body acceleration measured onboard solo-flying pigeons (as model flapping fliers) can be used as qualitative proxies for turbulence. A range of pressure and acceleration proxies performed well when tested against independent turbulence measurements from a tri-axial anemometer mounted onboard an ultralight flying the same route, with stronger turbulence causing increasing vertical displacement. The best proxy for turbulence also varied with estimates of both convective velocity and wind shear. The approximately linear relationship between most proxies and turbulence levels suggests this approach should be widely applicable, providing insight into how turbulence changes in space and time. Furthermore, pigeons were able to fly in levels of turbulence that were unsafe for the ultralight, paving the way for the study of how freestream turbulence affects the costs and kinematics of animal flight.
Repeatability and timing of tropical influenza epidemics
Authors: Servadio Joseph L , Thai Pham Quang , Choisy Marc , Boni Maciej F
Published: November 2022

Much of the world experiences influenza in yearly recurring seasons, particularly in temperate areas. These patterns can be considered repeatable, occurring predictably and consistently. In tropical areas, including southeast Asia, this consistency is less conspicuous. This study aimed to assess repeatability of influenza in Vietnam. A mathematical model was developed incorporating periods of increased transmission, and fit to data from sentinel hospitals throughout Vietnam as well as four temperate locations. Repeatability was evaluated through the variance of the timings of peak transmission. Model fits from Vietnam show high variance (sd = 70-171) in peak transmission timing; peaks occurred at irregular intervals and throughout different times of year. Fits from temperate locations showed regular, annual epidemics in winter months, with low variance in peak timings (sd = 33-74). This suggests that influenza patterns are not repeatable or seasonal in Vietnam. Influenza prevention in Vietnam therefore cannot rely anticipating regularly occurring outbreaks.
An unbroken network of interactions connecting flagellin domains is required for motility in viscous environments
Authors: Nedeljković Marko , Postel Sandra , Bonsor Daniel , Xing Yingying , Jacob Neil , Schuler William J. , Sundberg Eric J.
Published: November 2022

In its simplest form, bacterial flagellar filaments are composed of flagellin proteins with just two helical inner domains, which together comprise the filament core. Although this minimal filament is sufficient to provide motility in many flagellated bacteria, most bacteria produce flagella composed of flagellin proteins with one or more outer domains arranged in a variety of supramolecular architectures radiating from the inner core. Flagellin outer domains are known to be involved in adhesion, proteolysis and immune evasion but have not been thought to be required for motility. Here we show that in thePseudomonas aeruginosaPOA1 strain, a bacterium that forms a ridged filament on account of the arrangement of the two outer domains of its flagellin protein, motility is categorically dependent on these flagellin outer domains. Moreover, a comprehensive network of intermolecular interactions connecting the inner domains to the outer domains, the outer domains to one another, and the outer domains back to the inner domain filament core, is required for motility. This inter-domain connectivity confers PAO1 flagella with increased stability, essential for its motility in viscous environments. Additionally, we find that such ridged flagellar filaments are not unique toPseudomonasbut are, instead, present throughout diverse bacterial phyla.
Kinesin family motors modify transcription mediated by ERR1 using a conserved nuclear receptor box motif
Authors: Seneviratne A.M.P.B , Lidagoster S. , Valbuena-Castor S. , Lashley K. , Saha S. , Alimova A. , Kreitzer Geri
Published: November 2022

Kinesin family motors are microtubule (MT)-stimulated ATPases known best as transporters of cellular cargoes through the cytoplasm, regulators of MT dynamics, organizers of the mitotic spindle, and for insuring equal division of DNA during mitosis. Several kinesins have also been shown to regulate transcription by interacting with transcriptional cofactors and regulators, nuclear receptors, or with specific promotor elements on DNA. We previously showed that an LxxLL nuclear receptor box motif in the kinesin-2 family motor KIF17 mediates binding to the orphan nuclear receptor estrogen related receptor alpha (ERR1) and is responsible for the suppression of ERR1-dependent transcription by KIF17. Analysis of all kinesin family proteins revealed that multiple kinesins contain this LxxLL motif, raising the question as to whether additional kinesins motors contribute to regulation of ERR1. In this study, we interrogated the effects of multiple kinesins with LxxLL motifs on ERR1-mediated transcription. We demonstrate that the kinesin-3 motor KIF1B contains two LxxLL motifs, one of which binds to ERR1. In addition, we show that expression of a KIF1B fragment containing this LxxLL motif inhibits ERR1-dependent transcription by regulating nuclear entry of ERR1. We also provide evidence that the effects of expressing the KIF1B-LxxLL fragment on ERR1 activity are mediated by a mechanism distinct from that of KIF17. Because LxxLL domains are found in many kinesins, our data suggest an expanded role for kinesins in nuclear receptor mediated transcriptional regulation.
The human leukemic oncogene MLL-AF4 promotes hyperplastic growth of hematopoietic tissues inDrosophilalarvae
Authors: Johannessen Julie A. , Formica Miriam , Bråthen Nora Rojahn , Outa Amani Al , Aarsund Miriam , Therrien Marc , Enserink Jorrit M. , Knævelsrud Helene
Published: November 2022

MLL-rearranged leukemias are among the leukemic subtypes with poorest survival, and treatment options have barely improved over the last decades. Furthermore, despite increasing molecular understanding of the mechanisms behind these hematopoietic malignancies, this knowledge has had poor translation into the clinic. Identification of novel treatment methods is hampered by the lack of relevantin vivomodels that allow for rapid identification of actionable drug targets and small molecule inhibitors. Here, we report aDrosophila melanogastermodel system to explore the pathways affected inMLL-rearranged leukemia. We show that expression of the human leukemic oncogene MLL-AF4 in theDrosophilahematopoietic system resulted in increased levels of circulating hemocytes and an enlargement of the larval hematopoietic organ, the lymph gland. Strikingly, depletion ofDrosophilaorthologs of known interactors of MLL-AF4, such as DOT1L, rescued the leukemic phenotype. In agreement, treatment with small-molecule inhibitors of DOT1L also prevented the MLL-AF4-induced leukemia-like phenotype. Taken together, this model provides anin vivosystem to unravel the genetic interactors involved in leukemogenesis and offers a strategy for a prompt identification of potential therapeutic options for treatment ofMLL-rearranged leukemia.
Exosome-mediated viral nucleic acid presentation in a crustacean reveals innate immunity evolution from a novel perspective
Authors: Gong Yi , Hu Hang , Zhao Xinshan , Wei Weiqian , Zhang Ming , Tuan Tran Ngoc , Ma Hongyu , Zhang Yueling , Chan Kok-Gan , Li Shengkang
Published: November 2022

As an enduring hot topic in the field of innate immunity, apoptosis is widely considered as an effective approach to eliminate pathogenic microbes, and possesses crucial role during host-pathogen interactions. Recently, researchers have found that virus-containing host cells could transmit apoptotic signals to surrounding uninfected cells during infection, but the mechanism remains unclear. Here, we found that exosomes secreted by WSSV-infected mud crab hemocytes contain viral nucleic acid wsv277, which could be transported to the recipient cells and further expressed viral protein with phosphokinase activity. Besides, by using transcriptome, proteome, ChIP-seq and coIP techniques, the results revealed that wsv277 could activate the transcription and translation of apoptotic genes via interacting with CBF and EF-1α, so as to suppress the spread of virus infection by inducing apoptosis of the surrounding cells. Therefore, for the first time, our study proved that the components of DNA virus could be encapsulated into exosomes, and elucidated the mechanism of apoptotic signal transduction between cells from the perspective of exosome. Moreover, comparing those of invertebrates, we hypothesized that the innate immune system of vertebrate was weakened or degenerated, allowing exosomes to be employed by virus as the vehicle for immune escape.

Significance statement

Our study revealed that the components of DNA virus could be packaged and transmitted through the exosomes of lower invertebrates, which strongly demonstrated the diversity of exosome-mediated viral immunity and its universality in animals. Furthermore, we elucidated the mechanism of apoptotic signal transduction between cells from the perspective of exosome, and revealed a novel strategy for the host to cope with viral infection. Since exosome is an important innate immune regulation approach, we hypothesize that the innate immune system of vertebrates is weakened or degenerated, allowing exosomes to be employed by virus as the vehicle for immune escape.
Selective oxytocin receptor activation prevents prefrontal circuit dysfunction and social behavioral alterations in response to chronic prefrontal cortex activation in rats
Authors: Janz Philipp , Knoflach Frederic , Bleicher Konrad , Belli Sara , Biemans Barbara , Schnider Patrick , Ebeling Martin , Grundschober Christophe , Benekareddy Madhurima
Published: November 2022

Social behavioral changes are a hallmark of several neurodevelopmental and neuropsychiatric conditions, nevertheless the underlying neural substrates of such dysfunction remain poorly understood. Building evidence points to the prefrontal cortex (PFC) as one of the key brain regions that orchestrates social behavior. We used this concept with the aim to develop a translational rat model of social-circuit dysfunction, the chronic PFC activation model (CPA). Chemogenetic designer receptor hM3Dq was used to induce chronic activation of the PFC over 10 days, and the behavioral and electrophysiological signatures of prolonged PFC hyperactivity were evaluated. To test the sensitivity of this model to pharmacological interventions on longer timescales, and validate its translational potential, the rats were treated with our novel highly selective oxytocin receptor (OXTR) agonist RO6958375, which has a significantly improved pharmacokinetic profile over oxytocin. CPA rats showed reduced sociability in the three-chamber sociability test, and a concomitant decrease in neuronal excitability and synaptic transmission within the PFC as measured by electrophysiological recordings in acute slice preparation. Sub-chronic treatment with a low dose of the novel OXTR agonist following CPA interferes with the emergence of PFC circuit dysfunction, abnormal social behavior and specific transcriptomic changes. These results demonstrate that sustained PFC hyperactivity modifies circuit characteristics and social behaviors in ways that can be modulated by selective OXTR activation and that this model may be used to understand the circuit recruitment of prosocial therapies in drug discovery.
Different outcomes of neonatal and adult Zika virus infection on startle reflex and prepulse inhibition in mice
Authors: Souza Isis N. O. , Andrade Brenda S. , Frost Paula S. , Neris Romulo L. S. , Gavino-Leopoldino Daniel , Da Poian Andrea T. , Assunção-Miranda Iranaia , Figueiredo Claudia P. , Clarke Julia R. , Neves Gilda A.
Published: November 2022

Zika virus (ZIKV) infection causes severe neurological consequences in both gestationally-exposed infants and adults. Sensorial gating deficits strongly correlate to the motor, sensorial and cognitive impairments observed in ZIKV-infected patients. However, to date, no startle response or prepulse inhibition (PPI) assessment has been made in patients or animal models. In this study, we identified different outcomes for the age of infection and sex in wild-type mice: neonatally infected animals presented an increase in PPI and startle latency in both sexes, while adult infected males presented lower startle amplitude but preserved PPI. Our data further the understanding of the functional impacts of ZIKV on the developing and mature nervous system, which could help explain other behavioral and cognitive alterations caused by the virus. With this study, we support the use of startle reflex testing in ZIKV exposed patients, especially infants, allowing for early detection of functional neuromotor damage and early intervention.
The in-tissue molecular architecture of β-amyloid in the mammalian brain
Authors: Leistner Conny , Wilkinson Martin , Burgess Ailidh , Goodbody Stanley , Xu Yong , Deuchars Susan , Radford Sheena E. , Ranson Neil A. , Frank René A. W.
Published: November 2022

Amyloid plaques composed of extracellular focal deposition of Aβ fibrils are a hallmark of Alzheimer’s disease (AD). Cryo-EM structures of Aβ fibrils purified from human AD brain tissue post mortem have recently been determined. However, the molecular architecture of amyloid plaques in the context of fresh, unfixed mammalian brain tissue is unknown. Here, using cryogenic correlated light and electron tomography we report the native,in situmolecular architecture of Aβ fibrils in the brain of a mouse model containing the Arctic familial AD mutation (AppNL-G-F) and an atomic model of Arctic Aβ fibril purified from the brains of these animals. We show that in-tissue Aβ fibrils are arranged in a lattice or in parallel bundles within a plaque, and are interdigitated by subcellular compartments, exosomes, extracellular droplets and extracellular multilamellar bodies. At the atomic level, the Arctic Aβ fibril differs significantly from earlier structures of Aβ amyloid extracted fromAppNL-Fmice models and human AD brain tissue, showing a striking effect of the Arctic mutation (E22G) on fibril structure. Cryo-electron tomography ofex vivopurified and in-tissue amyloid revealed an ensemble of additional fibrillar species, including thin protofilament-like rods and branched fibrils. Together, these results provide a structural model for the dense network architecture that characterises β-amyloid plaque pathology.
Tailoring confocal microscopy for in-cell photophysiology studies
Authors: Storti Mattia , Hsine Haythem , Uwizeye Clarisse , Bastien Olivier , Yee Daniel , Chevalier Fabien , Giustini Cécile , Béal Daniel , Decelle Johan , Curien Gilles , Tolleter Dimitri , Finazzi Giovanni
Published: November 2022

Photoautotrophs environmental responses have been extensively studied at the organism and ecosystem level. However, less is known about their photosynthesis at the single cell level. This information is needed to understand photosynthetic acclimation processes, as light changes as it penetrates cells, layers of cells or organs. Furthermore, cells within the same tissue may behave differently, being at different developmental/physiological stages. Here we describe a new approach for single-cell and subcellular photophysiology based on the customisation of confocal microscopy to assess chlorophyll fluorescence quenching by the saturation pulse method. We exploit this setup to: i. reassess the specialisation of photosynthetic activities in developing tissues of non-vascular plants; ii. identify a specific subpopulation of phytoplankton cells in marine photosymbiosis, which are consolidating metabolic connections with their animal hosts, and iii. testify to the link between light penetration and photoprotection responses inside the different tissues that constitute a plant leaf anatomy.

Motivation

Visualising photosynthetic responses in 3D is essential for understanding most acclimation processes, as light changes within photosynthetic tissues as it penetrates the absorbing/diffusing layers of the cells. To achieve this goal, we developed a new imaging workflow merging confocal microscopy and saturating pulse chlorophyll fluorescence detection. This method applies to samples characterised by increasing complexity and its simplicity will contribute to its widespread use in plant and microalgae photoacclimation studies.