bluuebunny/crossref_metadata_2025 huggingface dataset:
MICROVASCULAR CHANGES IN TREATMENT-NAÏVE NONEXUDATIVE MACULAR NEOVASCULARIZATION COMPLICATED BY EXUDATION
Authors: Crincoli Emanuele , Catania Fiammetta , Labbate Gaia , Sacconi Riccardo , Ferrara Silvia , Parravano Mariacristina , Costanzo Eliana , Querques Giuseppe
Published: June 2024

Purpose:

To assess differences in choriocapillaris (CC) and macular neovascularization (MNV) optical coherence tomography angiography quantitative parameters between long-term persistently nonexudative MNVs (NE-MNVs) and long-term activated NE-MNVs in age-related macular degeneration.

Methods:

Age-related macular degeneration patients with treatment-naïve NE-MNVs with >2 years of follow-up and no evidence of exudation within the first 6 months from diagnosis were retrospectively recruited. Two groups were considered according to the occurrence (EX group) or not (NE group) of exudation within the first 2 years of follow-up. Segmentation of the MNV and of the perilesional CC were obtained from enface optical coherence tomography angiography acquisitions at diagnosis and at 6-month follow-up. OCT B-scan images of the MNV were also collected. Fractal ratio was defined as the ratio between MNV fractal dimension (FrD) and CC FrD.

Results:

Fifty (50) eyes were included (20 EX group and 30 NE group). EX group showed higher flow deficit density and flow deficit number at the 6-month follow-up. It also showed higher MNV FrD, lower CC FrD, and higher fractal ratio at the 6-month follow-up. The fractal ratio significantly increased at 6-month acquisitions in the EX group, showing an area under the ROC curves of 0.887 (95% CI 0.869–0.922).

Conclusion:

Fractal ratio at 6 months can predict exudation risk of MNV within 2 years from diagnosis. This suggests increased structural complexity of the NE-MNV accompanied by progressive capillary rarefaction of the perilesional CC as a key driving factor for the development of exudation in NE-MNV.
Assessing the Burden of Respiratory Syncytial Virus-related Bronchiolitis in Primary Care and at 15-Day and 6-Month Follow-up Before Prophylaxis in France: A Test-negative Study
Authors: Rybak Alexis , Cohen Robert , Bangert Mathieu , Kramer Rolf , Delobbe Jean-François , Deberdt Patrice , Cahn-Sellem Fabienne , Béchet Stéphane , Levy Corinne
Published: June 2024

Objective:

To assess the burden of respiratory syncytial virus (RSV)-related bronchiolitis in primary care and at 15 days and 6 months after a primary care visit.

Study Design:

In this test-negative study, children <2 years old with a first episode of bronchiolitis were prospectively enrolled by 45 ambulatory pediatricians in France from February 2021 to April 2023. RSV was assessed with a rapid antigen detection test. The burden of the disease was assessed with a questionnaire, including quality of life (PedsQL 1.0 Infant Scales), at 15-day and 6-month follow-up. Children with a positive RSV test result (RSV+) were compared to those with a negative test result (RSV−).

Results:

Among the 1591 children enrolled, 750 (47.1%) were RSV+. At 15 days follow-up (data availability: 69%), as compared with RSV− children, RSV+ children more frequently had fever (20.5% vs. 13.7%, P = 0.004) and decreased food intake (27.0% vs. 17.4%, P < 0.001) during the last 3 days. They had higher rates of hospitalization (11.8% vs. 5.8%, P < 0.001), childcare absenteeism (83.5% vs. 66.1%, P < 0.001) and parents who had to stop working to care for them (59.1% vs. 41.0%, P < 0.001) as well as lower quality of life (median PedsQL score 76.2 vs. 78.4, P = 0.03). At 6 months (data availability: 48.5%), the 2 groups did not differ in proportion of medical attendance, hospitalization, antibiotic treatment or quality of life.

Conclusion:

RSV+ children experienced much more severe disease and follow-up family and societal burden than RSV− children. These data may be used as baseline data as RSV prophylaxis is about to be implemented.
Subsequent Complications of Pediatric Patients With Osteomyelitis and Accompanying Subperiosteal Abscess
Authors: Hosokawa Takahiro , Deguchi Kuntaro , Takei Haruka , Sato Yumiko , Tanami Yutaka , Oguma Eiji
Published: June 2024

Background:

Subperiosteal abscesses (SAs) are a complication of osteomyelitis that requires surgical intervention. This study aimed to characterize the occurrence of subsequent complications in pediatric patients with osteomyelitis and accompanying SA.

Methods:

Fourteen pediatric patients with SAs were included. We recorded clinical information, including age at diagnosis, interval (days) between the onset of symptoms and diagnosis, location of SAs (long/flat bone), pathogens [methicillin-resistant Staphylococcus aureus (MRSA)/non-MRSA], treatment period (days) and any subsequent complications. Patients were classified based on SAs with or without complications. Mann-Whitney U and Fisher exact tests were used for statistical analyses, and data are expressed as median and interquartile range.

Results:

Six patients (42.9%) had subsequent complications. There were significant differences in location of SAs between these two groups (long/flat bone, with versus without complication = 6/0 versus 3/5; P = 0.031). No significant differences were observed between the groups in terms of age [with versus without complication = 13.8 (9.7–24.5) versus 556.3 (5.0–107.8) months; P = 0.491], the interval (days) between symptoms onset and diagnosis [with versus without complications = 5 (1–10) versus 5 (3–6.5) days; P = 0.950], pathogenesis (MRSA/non-MRSA, with versus without complication = 4/2 versus 2/6; P = 0.277) and treatment period [with versus without complication = 50.5 (31–57) versus 29 (24.5–41.5) days; P = 0.108].

Conclusions:

Pediatric patients with SAs in the long bones have a higher likelihood of experiencing subsequent complications than those with SAs in flat bones. Physicians should carefully manage this vulnerable patient group.
Pneumococcal Colonization in Children With Persistent Asthma: A Retrospective Cohort
Authors: Olarte Liset , Banerjee Dithi , Swanson Douglas , Tabakh Jennifer , Lee Brian , Harrison Christopher J. , Selvarangan Rangaraj
Published: June 2024

Background:

Asthma is the most common chronic medical condition among children ≥5 years of age with invasive pneumococcal disease. How asthma or its management affects pneumococcal colonization is not fully understood. Our objective was to compare pneumococcal colonization rates between children with persistent asthma and children without asthma, and to characterize the pneumococcal serotype distribution.

Methods:

We used nasal mid-turbinate samples obtained per routine care from 5- to 18-year-old children with upper respiratory symptoms from November to April (respiratory seasons) of 2017 to 2018 and 2018 to 2019 in Kansas City, United States. Pneumococcal immunization status, prior antibiotic use and other clinical data were collected. Samples were tested for pneumococcal colonization by real-time polymerase chain reaction targeting lytA gene. Positive samples underwent multiplex serotype-specific polymerase chain reaction assays to determine the serotype.

Results:

Of 363 children (120 with persistent asthma and 243 without asthma), 87.6% were 5 to 10 years old, 50.1% were female and 74.1% received ≥3 doses of a pneumococcal conjugate vaccine. The pneumococcal colonization rate was lower in children with persistent asthma than in children without asthma (10% versus 18.9%, P = 0.03). The odds of colonization were lower in children with persistent asthma [OR 0.4 (95% confidence interval: 0.2–0.9)] after adjusting for demographic and clinical data. Pneumococcal serotype was confirmed in 77.6% of positive samples; 35.6% of those samples corresponded to PCV13 serotypes and 64.4% to non-PCV13 serotypes. The most common serotypes were 19F (15%), 3 (13%) and 6C/6D (11%).

Conclusions:

Children with persistent asthma had lower rates of pneumococcal colonization than children without asthma when seeking care for respiratory symptoms.
Incidence, Risk Factors, Short-term Outcomes, and Microbiome of Ventilator-associated Pneumonia in Very-low-birth-weight Infants: Experience at a Single Level III Neonatal Intensive Care Unit
Authors: Huang Jane , Cayabyab Rowena , Cielo Mikhaela , Ramanathan Rangasamy
Published: June 2024

Background:

Ventilator-associated pneumonia (VAP) is a common hospital-acquired infection in neonates on invasive mechanical ventilation, resulting in high morbidity and mortality. The objective of this study is to determine the incidence, risk factors, short-term outcomes and microbiome associated with VAP in very-low-birth-weight (VLBW) infants born at <32 weeks of gestational age (GA).

Methods:

Retrospective study of intubated VLBW infants born at <32 weeks of GA admitted to the Los Angeles General Medical Center neonatal intensive care unit from July 2015 to July 2021 who had routine tracheal aspirate cultures obtained. Neonates were retrospectively classified into 3 groups, confirmed VAP, suspected VAP and no VAP, for comparison of risk factors, outcomes and airway microbial colonization.

Results:

Eighty-seven infants met inclusion criteria with a mean GA of 26.1 ± 1 weeks and mean birth weight of 812 ± 281 g. The incidence of VAP was 7.8 per 1000 ventilator days, and the most common causative organisms were Gram-positive organisms (39%), predominantly coagulase-negative Staphylococcus. Duration of postnatal dexamethasone exposure predicted VAP compared to no VAP (coefficient, 0.31; 95% CI 0.03–0.59; P = 0.03) after adjusting for duration of intubation, surfactant use and antenatal steroid exposure. Infants with VAP had higher rate of grade 2/3 bronchopulmonary dysplasia (P = 0.03) and longer hospital stay (P = 0.04).

Conclusions:

VAP occurs at a high rate in VLBW infants who are exposed to prolonged dexamethasone use. It is predominantly caused by Gram-positive organisms.
Clinically relevant cut-points for changes in the Liver Frailty Index are associated with waitlist mortality in patients with cirrhosis
Authors: Wang Melinda , Shui Amy M. , Ruck Jessica , Huang Chiung-Yu , Verna Elizabeth C. , King Elizabeth A. , Ladner Daniela P. , Ganger Daniel , Kappus Matthew , Rahimi Robert , Tevar Amit D. , Duarte-Rojo Andres , Lai Jennifer C.
Published: June 2024

Physical frailty is a critical determinant of mortality in patients with cirrhosis and can be objectively measured using the Liver Frailty Index (LFI), which is potentially modifiable. We aimed to identify LFI cut-points associated with waitlist mortality. Ambulatory adults with cirrhosis without HCC awaiting liver transplantation from 9 centers from 2012 to 2021 for ≥3 months with ≥2 pre-liver transplantation LFI assessments were included. The primary explanatory variable was the change in LFI from first to second assessments per 3 months (∆LFI); we evaluated clinically relevant ∆LFI cut-points at 0.1, 0.2, 0.3, and 0.5. The primary outcome was waitlist mortality (death or delisting for being too sick), with transplant considered as a competing event. Among 1029 patients, the median (IQR) age was 58 (51–63) years; 42% were female; and the median lab Model for End-Stage Liver Disease-Sodium at first assessment was 18 (15–22). For each 0.1 improvement in ∆LFI, the risk of overall mortality decreased by 6% (cause-specific hazard ratio: 0.94, 95% CI: 0.92–0.97, p < 0.001). ∆LFI was associated with waitlist mortality at cut-points as low as 0.1 (cause-specific hazard ratio: 0.63, 95% CI: 0.46–0.87) and 0.2 (HR: 0.61, 95% CI: 0.42–0.87). An improvement in LFI per 3 months as small as 0.1 in the pre-liver transplantation period is associated with a clinically meaningful reduction in waitlist mortality. These data provide estimates of the reduction in mortality risk associated with improvements in LFI that can be used to assess the effectiveness of interventions targeting physical frailty in patients with cirrhosis.
Endoscopic therapies for bariatric surgery complications
Authors: Yakout Abdelrahman , Elli Enrique F. , Kumbhari Vivek , Bakheet Nader
Published: June 2024

Purpose of review

The aim of this review is to present the current state of the field, highlight recent developments, and describe the clinical outcomes of endoscopic therapies for bariatric surgery complications.

Recent findings

The field of interventional endoscopy now presents a range of minimally invasive procedures for addressing postbariatric complications. Lumen-opposing metal stents have emerged as a reliable solution for managing gastrojejunal strictures following Roux-en-Y gastric bypass, whether with or without associated leaks. Additionally, they serve as a conduit for performing endoscopic retrograde cholangiopancreatography (ERCP) post-RYGB via EUS-directed ERCP (EDGE). Gastric peroral endoscopic myotomy, originally designed for gastroparesis, has demonstrated effectiveness in treating postgastric sleeve stenosis, particularly the challenging helical stenosis cases. Furthermore, innovative endoscopic antireflux techniques are showing encouraging outcomes in addressing gastroesophageal reflux disease (GERD) following sleeve gastrectomy. Additionally, several modifications have been proposed to enhance the efficacy of transoral outlet reduction (TORe), originally developed to treat weight regain due to gastrojejunal anastomotic issues post-RYGB.

Endoscopic management of bariatric surgery complications is continuously evolving. The development of new techniques and devices allows endoscopists to provide novel, minimally invasive alternatives that were not possible in the near past. Many techniques, however, are limited to expert centers because they are technically demanding, and specialized training in bariatric endoscopy is still required.
The environmental impacts of anesthesia
Authors: Grunert Matthew , Hunt Megan F. , Decker Mary
Published: June 2024

Purpose of review

The healthcare sector has a substantial environmental footprint, and the delivery of anesthesia contributes significantly. Inhaled anesthetics themselves are potent greenhouse gases, unused intravenous medication exert toxic effects on the environment, and the increasing reliance on single-use devices has led to an ever-growing amount of solid waste produced in operating rooms. This review discusses many of these environmental impacts and suggests practices to mitigate the environmental footprint of anesthetic practice.

Recent findings

The choice of anesthesia maintenance has significant environmental implications, with nitrous oxide and desflurane having the highest carbon footprint of all anesthetic agents. Using low fresh gas flows and supplementing or replacing inhalational agents with propofol leads to a significant reduction in emissions. Many intravenous anesthetic agents pose a risk of environmental toxicity, and efforts should be made to decrease medication waste and ensure appropriate disposal of unused medications to minimize their environmental impacts. Additionally, consideration should be given to replacing single-use devices in the operating rooms with reusable alternatives that are often both environmentally and economically superior. And solid waste generated in the operating room should be segregated thoughtfully, as processing regulated medical waste is a highly energy-intensive process.

Significant opportunities exist to improve the environmental footprint of anesthesia practice, and with the rapidly worsening climate crisis, the importance of implementing changes is greater than ever.
Phantom sensation in genital gender-affirming surgery: a narrative review
Authors: Ferrin Peter C. , Burghardt Elliot , Peters Blair R.
Published: June 2024

Purpose of review

To review findings related to phantom genital sensation, emphasizing phantom sensation in the transgender and gender diverse (TGD) population. We discuss prevalence, presentation and potential implications for sensory outcomes in genital gender-affirming surgery.

Recent findings

There is a high prevalence of phantom genital sensations in the TGD population. The prevalence varies by body part, approaching 50% in the most frequently reported transgender phantom – the phantom penis. Unlike genital phantoms that occur after trauma or surgery which are often painful, transgender phantoms are typically neutral and often erogenous in experience. Phantom sensation in the TGD population can be an affirming experience and important part of sexual well being and embodiment.

Recent studies have begun to characterize the prevalence and presentations of phantom genital sensations in TGD people, informing our evolving understanding of the sensory experiences of the transgender and gender diverse population. Targeting integration of these centrally-mediated phantom genital sensations with the peripherally generated sensation from genital stimulation may represent one potential avenue to improve sensation and embodiment following genital gender-affirming surgical procedures. Additionally, emerging techniques in modern peripheral nerve surgery targeting phantom pain may offer potential treatment options for painful phantom sensation seen after cases of genital surgery or trauma.
Prolactinoma: Navigating the Dual Challenge of Side Effects and Treatment Strategies - A Comprehensive Review
Authors: Yogeeta Fnu , Rauf Sameer Abdul , Devi Muskan , Imran Komal , Ahmed Rubayyi , Aruwani Prashant K. , Saad Muhammad , Tooba Fnu , Hashmani Faiza Zehra , Ibrahim Mufliha , Kumar Neeraj , Shah Hussain Haider , Hussain Tooba , Haque Md Ariful
Published: June 2024

This narrative review provides a succinct exploration of prolactinoma, the most common pituitary adenoma, focusing on its epidemiology, clinical manifestations, and therapeutic interventions. Beginning with an overview of its prevalence and aetiology, the review delves into the gender distribution and familial associations of prolactinoma. Clinical presentations, including endocrine disruptions, reproductive health issues, and metabolic disturbances, are examined, emphasizing their impact on hormonal regulation and cardiovascular health. The narrative then navigates through pharmacological treatments, surgical interventions, and radiation therapy, highlighting their efficacy, side effects, and long-term management challenges. Strategies to mitigate side effects and optimize treatment outcomes are discussed, emphasizing the importance of multidisciplinary collaboration in prolactinoma management. This review is a concise yet comprehensive resource for healthcare professionals and researchers, providing insights into prolactinoma’s clinical complexities and therapeutic nuances to guide optimal patient care strategies.
Hidden harm
Authors: Geist Rebecca , Gary Mary Annette , Kiper Valerie , Cockerell Kimber
Published: June 2024

Nurses are often the first to observe maltreatment and identify potential symptoms of this disorder. Proper vigilance, assessment, and mitigation strategies are essential to prioritize the well-being of dependents.
Physical Therapy and Aminopyridine for Downbeat Nystagmus Syndrome: A Case Report
Authors: Cornforth Elizabeth , Schmahmann Jeremy D.
Published: June 2024

Background and purpose:

Individuals with downbeat nystagmus (DBN) syndrome present with DBN, dizziness, blurred vision, and unsteady gait. Pharmacological intervention with 4-aminopyridine (4-AP) may be effective in improving oculomotor function, but there is minimal evidence to date that it improves gait. This suggests the possible benefit of combining pharmacotherapy with physical therapy to maximize outcomes. This case report documents improvements in gait and balance after physical therapy and aminopyridine (AP) in an individual with DBN syndrome.

Case description:

The patient was a 70-year-old man with a 4-year history of worsening dizziness and imbalance, diagnosed with DBN syndrome. He demonstrated impaired oculomotor function, dizziness, and imbalance, which resulted in falls and limited community ambulation.

Intervention:

The patient completed a customized, tapered course of physical therapy over 6 months. Outcome measures included the 10-meter walk test, the Timed Up and Go (TUG), the Dynamic Gait Index (DGI), and the modified clinical test of sensory integration and balance.

Outcomes:

Improvements exceeding minimal detectable change were demonstrated on the TUG and the DGI. Gait speed on the 10-meter walk test did not change significantly, but the patient was able to use a cane to ambulate in the community and reported no further falls.

Discussion:

Controlled studies are needed to explore the potential for AP to augment physical therapy in people with DBN syndrome. Physical therapists are encouraged to communicate with referring medical providers about the use of AP as pharmacotherapy along with physical therapy for individuals with DBN syndrome.
Pelvic Floor Rehabilitation After Rectal Cancer Surgery
Authors: Bosch Noes Margaretha , Kalkdijk-Dijkstra Jenneke Aaltje , van Westreenen Hendrik Leendert , Broens Paul ma , Pierie Eugène Nicolas Jean , van der Heijden Joost Albertus Gerardus , Klarenbeek Bastiaan Rijk ,   On behalf of the FORCE trial group
Published: June 2024

Objective:

To evaluate the effects of pelvic floor rehabilitation (PFR) after low anterior resection (LAR) at 1-year follow-up.

Background:

After LAR, with restoration of bowel continuity, up to 90% of patients develop anorectal dysfunction, significantly impacting their quality of life (QoL). However, standardized treatment is currently unavailable. The FORCE trial demonstrated the beneficial effects of PFR after 3 months regarding specific domains of the Fecal Incontinence QoL (FIQL) questionnaire and urgency compared with usual care.

Methods:

The FORCE trial is a multicenter, two-arm, randomized clinical trial. All patients undergoing LAR were randomly assigned to receive either usual care or a standardized PFR program. The primary outcome measure is the Wexner incontinence score, and the secondary endpoints included the low anterior resection syndrome score, the European Organization for Research and Treatment of Cancer colorectal-specific QoL questionnaire, and health and FIQL. Assessments were conducted at baseline before randomization, at 3 months and 1-year follow-ups.

Results:

A total of 86 patients were included (PFR: n = 40, control: n = 46). After 1 year, PFR did not significantly improve Wexner incontinence scores (PFR: -3.33, 95% CI: -4.41 to -2.26, control: -2.54, 95% CI: -3.54 to -1.54, P = 0.30). Similar to the 3-month follow-up, patients without near-complete incontinence at baseline showed a sustained improvement in fecal incontinence (PFR: -2.82, 95% CI: -3.86 to -1.76, control: -1.43, 95% CI: -2.36 to -0.50, P = 0.06). Significant improvement was reported in the FIQL domains Lifestyle (PFR: 0.51, control: -0.13, P = 0.03) and Coping and Behavior (PFR: 0.40, control: -0.24, P = 0.01).

Trial registration:

Netherlands Trial Registration, NTR5469, registered on September 3, 2015.

Conclusions:

At 1-year follow-up, no significant differences were found in fecal incontinence scores; however, PFR was associated with improved FIQL compared with usual care.
Education of adult type 1 diabetes patients in a diabetes ward setting: a best practice implementation project
Authors: Kania Michał , Suduł Paulina , Wilk Magdalena , Szopa Magdalena , Katra Barbara , Małecki Maciej T. , Poklepović Peričić Tina , Prill Robert , Klugarová Jitka , Vrbova Tereza , Klugar Miloslav , Leśniak Wiktoria , Bała Małgorzata M.
Published: June 2024

Introduction and objectives:

Type 1 diabetes is an autoimmune disease that destroys insulin-producing cells in the pancreas. Education is the cornerstone of effective diabetes care. In this implementation project, we aimed to improve compliance with best practices regarding type 1 diabetes educational interventions for adult hospitalized patients.

Methods:

This project was guided by the JBI Evidence Implementation Framework. A baseline audit was conducted involving 20 nurses and 20 type 1 diabetes patients who received regular educational measures. Areas of non-compliance were identified and an improvement strategy was implemented. A follow-up audit was then conducted to evaluate the effectiveness of the improvement strategy. The project was conducted in Poland in 2021 in a tertiary referral unit that specializes in the diagnosis and treatment of diabetes.

Results:

Substantial improvements were noted for all audit criteria after the implementation of strategies to address areas of non-compliance. Use of the education program improved from 0% to 100%. Compliance regarding patients receiving handouts and personalization of the program increased to 100%. We observed a significant improvement from 0% to 80% in the structuring of the program content.

Conclusions:

This project successfully improved the quality of education provided for type 1 diabetes patients in all relevant areas. We devised an education program, covering important aspects of diabetes education, with the patients reporting increased satisfaction with the personalized educational measures during their hospital stay.

Spanish abstract:

http://links.lww.com/IJEBH/A215
Rapid and prolonged antidepressant and antianxiety effects of psilocybin, lysergic acid diethylamide, ayahuasca, and 3, 4-methylenedioxy-methamphetamine. A systematic review and meta-analysis of randomized controlled trials
Authors: Fluyau Dimy , Kailasam Vasanth Kattalai , Revadigar Neelambika
Published: June 2024

Background

Hallucinogens attract research as alternatives to the commonly used medications to treat major depressive and anxiety disorders.

Aims

Assess hallucinogens’ efficacy for managing depressive and anxiety symptoms and evaluate their safety profiles.

Method

In five databases, we searched for randomized controlled trials of hallucinogens targeting depressive and anxiety symptoms. We performed a meta-analysis using a random effects model when data permitted it. The protocol of the review is registered in PROSPERO; CRD42022341325.

Results

Psilocybin produced a rapid and sustained reduction in depressive and anxiety symptoms in patients with major depressive disorder, severe, and in patients with life-threatening cancer. A decrease in depressive symptoms was observed with 3, 4-methylenedioxymethamphetamine (MDMA), primarily in patients with life-threatening cancer, autism spectrum disorder, and post-traumatic stress disorder. MDMA reduced social anxiety symptoms. However, MDMA’s effect size was either negligible or negative for anxiety symptoms overall. Ayahuasca reduced depressive symptoms in individuals with treatment-resistant major depressive and personality disorders. Lysergic acid diethylamide (LSD) reduced anxiety symptoms in individuals with life-threatening cancer.

Psilocybin’s adverse effects were noticeable for elevated blood pressure, headaches, and panic attacks. For MDMA, elevated blood pressure, headaches, panic attacks, and feeling cold were noticeable.

Conclusions

Psilocybin, MDMA, ayahuasca, and LSD appear to have the potential to reduce depressive and anxiety symptoms. Adverse effects are noticed. Rigorous randomized controlled studies with larger sample sizes utilizing outcome measures instruments with better reliability and validity are warranted.
Feedback Control of Neuronal Excitability and Epileptiform Bursting using a Photocaged Adenosine A1Agonist
Authors: Craey Erine , Van Calenbergh Serge , Spanoghe Jeroen , Vergaelen Marijke , Larsen Lars E. , Carrette Evelien , Delbeke Jean , Vonck Kristl , Boon Paul , Wadman Wytse J. , Raedt Robrecht
Published: June 2024

Adenosine is a potent regulator of neurotransmission and neuronal excitability through activation of Giprotein-coupled adenosine A1receptors (A1Rs). It has gained interest as a potential anticonvulsant due to its endogenous involvement in ending ongoing seizure activity.

A recently developed coumarin-caged derivative of the A1R agonist N6-cyclopentyl-adenosine (CPA), cCPA, was used for photo-uncaging of CPA with millisecond flashes of 405 nm light. At population level, CPA reduces Schaffer Collateral stimulated extracellular dendritic field potentials (FPs) in the CA1 region of the hippocampus with an ED50of 44.1±2.8 nM and a Hill coefficient of 3. Response onset is CPA dependent and takes less than seconds, while recovery is CPA independent with a time constant of around 20 minutes.

A closed-loop feedback system used the amplitude of evoked dendritic FPs to photorelease CPA and was able to control FP amplitude to user defined levels between 10% and 90% of baseline level. In the acute elevated potassium model of epilepsy raising extracellular K+to 8.5 mM enhances neuronal excitability and induces regularly occurring epileptiform bursts, but FPs evoked with low intensity could still continuously monitor excitability without interfering with bursting.

In this model the closed-loop system that controlled CPA release, was able to suppress epileptiform bursting, while maintaining an acceptable level of functional neurotransmission. Including in the control algorithm a second parameter that combined population spike amplitude and number of population spikes, enabled the system to automatically find a level of functional neurotransmission that was just below the threshold for multiple spiking and epileptiform bursting.

The combination of photopharmacological adenosinergic modulation with real-time FP monitoring provides a first step towards closed-loop precision treatment for diseases related to neuronal hyperexcitability such as epilepsy.
Strand asymmetry in the repair of replication dependent double-strand breaks
Authors: Kimble Michael T , Sane Aakanksha , Reid Robert JD , Johnson Matthew J , Rothstein Rodney , Symington Lorraine S
Published: June 2024

Single-strand breaks (SSBs) are one of the most common endogenous lesions and have the potential to give rise to cytotoxic double-strand breaks (DSBs) during DNA replication. To investigate the mechanism of replication fork collapse at SSBs and subsequent repair, we employed Cas9 nickase (nCas9) to generate site and strand-specific nicks in the budding yeast genome. We show that nCas9-induced nicks are converted to mostly double-ended DSBs during S-phase. We find that repair of replication-dependent DSBs requires homologous recombination (HR) and is independent of canonical non-homologous end joining. Consistent with a strong bias to repair these lesions using a sister chromatid template, we observe minimal induction of inter-chromosomal HR by nCas9. Using nCas9 and a gRNA to nick either the leading or lagging strand template, we carried out a genome-wide screen to identify factors necessary for the repair of replication-dependent DSBs. All the core HR genes were recovered in the screen with both gRNAs, but we recovered components of the replication-coupled nucleosome assembly (RCNA) pathway with only the gRNA targeting the leading strand template. By use of additional gRNAs, we find that the RCNA pathway is especially important to repair a leading strand fork collapse.
The GTPase-activating protein CG42795 is a potent neuronal regulator of ageing in Drosophila melanogaster
Authors: Falcsik Gergő , Kersztes Fanni , Balog Tünde Mónika , Kovács Tibor
Published: June 2024

Macroautophagy (hereafter referred to as autophagy) is an important self-renewal process in our cells, whereby potentially harmful cellular components are encapsulated within a double-membrane autophagosome and subsequently fused with a lysosome for degradation by acidic hydrolases. This lysosomal degradation process is essential for maintaining cellular homeostasis. Dysfunctional autophagy can lead to the accumulation of cytotoxic protein forms that contribute to the onset of age-related diseases. However, it has been proven that autophagy activity declines with age so it is therefore particularly important to stimulate autophagy during the lifespan of post-mitotic cells, such as neurons, where cell division is not a possibility in order to replace dead cells. Our research group aims to find new autophagy activation sites to stimulate the efficiency of acid degradation in neurons during ageing. One possibility is the stimulation of membrane fusion events, which are necessary for autophagic degradation, through the activation of small GTPase enzymes. Our previous results have shown that neuron-specific overexpression of the activated form of the Rab2 small GTPase has autophagy and lifespan-enhancing effects. In the present experiment, we used an RNA interference screen to investigate whether silencing 12 GTPase-activating proteins (GAPs) belonging to the TBC1 domain family can enhance Rab2 activation in theDrosophilanervous system. Several of the GAPs studied increased the number of Rab2-positive structures, 5 of which were selected for further screening. Our results suggest that neuronal silencing ofCG42795exerts an effect on autophagy, with the capacity to enhance the locomotor ability of animals and prolong lifespan. Our research has shown that the study of GAPs could be a promising new avenue of research for ageing researchers. Further analysis of CG42795 could lead to the development of potential autophagy activators.
Defining Structure-Function Relationships of Amphiphilic Excipients Enables Rational Design of Ultra-Stable Biopharmaceuticals
Authors: Prossnitz Alexander N. , Nguyen Leslee T. , Eckman Noah , Borkar Suraj , Tetef Samantha , Auzten Anton A. A. , Fuller Gerald G. , Appel Eric A.
Published: June 2024

Biopharmaceuticals are the fastest growing class of drugs in the healthcare industry, but their global reach is severely limited by their propensity for rapid aggregation. Currently, surfactant excipients such as polysorbates and poloxamers are used to prevent protein aggregation, which significantly extends shelf-life. Unfortunately, these excipients are themselves unstable, oxidizing rapidly into 100s of distinct compounds, some of which cause severe adverse events in patients. Here, we leverage the highly stable, well-defined, and modular nature of amphiphilic polyacrylamide-derived excipients to isolate the key mechanisms responsible for excipient-mediated protein stabilization. With a library of compositionally identical but structurally distinct amphiphilic copolymers, we quantify multiple relationships between polymer properties and fundamental phenomena to rationally design new ultra-stable surfactant excipients, increasing the stability of a notoriously unstable biopharmaceutical, monomeric insulin, by an order of magnitude. This comprehensive and generalizable understanding of excipient structure-function relationships represents a paradigm shift for the formulation of biopharmaceuticals, moving away from trial-and-error screening approaches towards rational design.

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The evolutionary dynamics of plant mating systems: how bias for studying ‘interesting’ plant reproductive systems could backfire
Authors: Meyer Elena M. , Galloway Laura F. , Eckert Andrew J.
Published: June 2024

Background and Aims

An “abominable mystery”: angiosperm sexual systems have been a source of both interest and frustration for the botanical community since Darwin. The evolutionary stability, overall frequency, and distribution of self-fertilization and mixed-mating systems have been explored in a variety of studies. However, there has been no recent study which directly addresses our knowledge of mating systems across families, the adequacy of existing data, or the potential for biases.

Scope

Here we present an updated dataset of mating systems across flowering plants covering 6,781 species and 212 families based on a synthesis of existing reviews and an original literature review using Web of Science. We assess the adequacy of this data by evaluating for bias indicating enrichment of certain families or sexual systems.

Key Results

We find that the vast majority of our data on mating systems comes from a small number of disproportionally sampled families, and that families with significant proportions of dioecious or monoecious species are much more likely to be undersampled.

Conclusions

Our results show that the frequency of selfing in angiosperms is overestimated, possibly due to increased research interest in selfing and mixed-mating systems. This suggests that systematic study bias may mean we know less about this vital facet of plant life than we think.
Morphology, biology and phylogeny ofXenos gadagkarisp.nov. (Strepsiptera: Xenidae): an endoparasite ofPolistes wattii(Hymenoptera: Vespidae)
Authors: Nain Deepak , Rana Anjali , Raychoudhury Rhitoban , Sen Ruchira
Published: June 2024

We report the morphology, biology and phylogeny of a new strepsipteran endoparasitic species:Xenos gadagkari,from the primitively eusocial waspPolistes wattiifrom Punjab, India. We report a high abundance of the endoparasite inP. wattiipopulation of our study area and provide the morphological description of adult males, male puparium and neotenic females. This species is sufficiently different from otherXenos spreported from various social wasps and therefore, constitutes a new species,X. gadagkariSen and Nain, sp. nov. Although there are a few reports of Strepsipteran parasites from India, this is the first confirmational report with a thorough description of aXenosspecies from the Indian population ofP. wattiiand underscores the need for further investigation of the diversity and distribution of this group in India. Our findings contribute to the growing body of knowledge onXenosand provide a foundation for future behavioural, microbial and molecular studies on this enigmatic group of insects.
The non-canonical thioreductase TMX2 is essential for neuronal survival during embryonic brain development
Authors: Dekker Jordy , Lam Wendy , van der Linde Herma C. , Ophorst Floris , de Konink Charlotte , Schot Rachel , Kremers Gert-Jan , Sanderson Leslie E. , Berdowski Woutje M. , van Woerden Geeske M. , Mancini Grazia M.S. , van Ham Tjakko J.
Published: June 2024

Biallelic variants in thioredoxin-related transmembrane 2 protein (TMX2) can cause a brain malformation of cortical development (MCD), characterized by primary microcephaly, polymicrogyria and pachygyria by an unknown mechanism. To better understand and visualize how TMX2 loss disrupts brain developmentin vivowe investigated the function of TMX2, using the zebrafish embryo as a model system. We generated zebrafish deficient forTMX2orthologtmx2b, which during the first 2 days post fertilization (dpf) showed normal behavioral activity and brain developmental hallmarks. From 3 dpf onwards however,tmx2bmutants failed to exhibit locomotor activity, which was accompanied by cell death primarily in the brain, but not in other organs or in the spinal cord. Strikingly, cell death intmx2bmutants occurs specifically in newborn neurons within a ∼1.5-hour timeframe, whereas neuronal progenitor and other glial cells are preserved, and could be suppressed by inhibiting neuronal activity.In vivoGCaMP6s calcium imaging showed a persistent ∼2-fold increase in calcium in neurons after the onset of cell death. This suggests that calcium homeostasis underlies thetmx2bmutant brain phenotype. Altogether, our results indicate that TMX2 is an evolutionary conserved, protective regulator essential specifically for newborn neurons to survive after their differentiation in the vertebrate embryonic brain.
Analysis of high-molecular-weight proteins using MALDI-TOF MS and Machine Learning for the differentiation of clinically relevantClostridioides difficileribotypes
Authors: Candela Ana , Rodriguez-Temporal David , Blázquez-Sánchez Mario , Arroyo Manuel J. , Marín Mercedes , Alcalá Luis , Bou Germán , Rodríguez-Sánchez Belén , Oviaño Marina
Published: June 2024

Clostridioides difficileis the main cause of antibiotic related diarrhea and some ribotypes (RT), such as RT027, RT181 or RT078, are considered high risk clones. A fast and reliable approach forC. difficileribotyping is needed for a correct clinical approach. This study analyses high-molecular-weight proteins forC. difficileribotyping with MALDI-TOF MS. Sixty-nine isolates representative of the most common ribotypes in Europe were analyzed in the 17,000-65,000m/zregion and classified into 4 categories (RT027, RT181, RT078 and ‘Other RTs’). Five supervised Machine Learning algorithms were tested for this purpose: K-Nearest Neighbors, Support Vector Machine, Partial Least Squares-Discriminant Analysis, Random Forest and Light-Gradient Boosting Machine. All algorithms yielded cross-validation results >70%, being RF and Light-GBM the best performing, with 88% of agreement. Area under the ROC curve of these two algorithms was >0.9. RT078 was correctly classified with 100% accuracy and isolates from the RT181 category could not be differentiated from RT027.
Effects of Resistance Training Combined with a Ketogenic Diet: A Systematic Review and Meta-Analysis
Authors: Sinott Luis Roberto , da Silva Clédia Silveira Flores , Scheer Alice Künzgen , Atrib Amanda Barbosa , Scheneider Augusto , Barros Carlos Castilho
Published: June 2024

Weight loss treatments require adherence to physical exercise and diet. Restrictive diets have been proposed for obesity treatment, including a ketogenic diet that are high in lipids, moderate in proteins, and low in carbohydrates. In recent years, there has been criticism of this diet because of the reduction in fat-free mass and, consequently, a reduction in basal energy expenditure, which is considered negative in obesity treatment. However, resistance training is known to promote skeletal muscle hypertrophy. The hypothesis for this review was: “Resistance training is sufficient to maintain lean mass during diets that cause ketosis.” Despite the slight reduction in lean mass identified in the meta-analysis, some authors reported no loss in physical performance. Others suggested that this difference in lean mass is associated with water loss in the participants, which aligns with a few studies that reported a final phase with carbohydrate reintroduction into the diet. Our results indicated physical exercise was an important tool for maintaining lean mass in individuals who consumed carbohydrate-restricted diets that cause ketosis.
Effects of Cannabidiol on Social Relating, Anxiety, and Parental Stress in Autistic Children: A Randomised Controlled Crossover Trial
Authors: Parrella Nina-Francesca , Hill Aron T. , Enticott Peter G. , Botha Tanita , Catchlove Sarah , Downey Luke , Ford Talitha C.
Published: June 2024

Cannabidiol (CBD), a non-intoxicating compound derived from the cannabis plant, has garnered increasing attention as a potential pharmacological therapeutic for autistic children. We conducted a randomised, double-blind, placebo-controlled, crossover trial to understand whether oral CBD oil can improve outcomes for this population, with a primary focus on social relating outcomes, along with anxiety and parental stress. A total of 29 children (18 male), aged 5 to 12 years (M = 9.62 years, SD = 2.05), diagnosed with autism spectrum disorder, completed the study. Participants received weight-based dosing of CBD oil (10 mg/kg/day) or placebo oil over two 12-week intervention periods (crossover), separated by an 8-week washout period. Outcome measures included the Social Responsiveness Scale-2 (SRS-2; primary outcome), PROMIS Social Relating, Anxiety, and Sleep, Developmental Behaviour Checklist-2 (DBC-2), Vineland 3, and Autism Parenting Stress Index (APSI; secondary outcomes). There was no significant effect observed for the primary outcome measure (SRS-2) for CBD oil relative to placebo oil after 12 weeks, (p=.125). Significant improvements were observed in secondary measures of social functioning (PROMIS-Social, DBC-2 Social Relating;p<.05) and anxiety symptoms (PROMIS Anxiety, DBC-2 Anxiety;p<.05), while there was also a reduction in parental stress (p<.05). Safety and tolerability data indicated that two children experienced gastrointestinal discomfort while taking CBD. This pilot trial represents preliminary evidence for the potential therapeutic effects of CBD in autism. While further research is needed to confirm and extend these findings, the results suggest that CBD may be a promising intervention for addressing one of autism’s core symptoms: social relating. Future studies with larger sample sizes are needed to fully evaluate the efficacy and safety of CBD for autistic children.
Overview of effects of motor learning strategies in neurological and geriatric populations: a systematic mapping review
Authors: Jie Li-Juan , Kleynen Melanie , Rothuizen Guus , Kal Elmar , Rothgangel Andreas , Braun Susy
Published: June 2024

Introduction

Motor learning plays a central role in neurological and geriatric rehabilitation. The wide range of motor learning strategies and increase in evidence can make it difficult to make informed decisions about the use of motor learning strategies in practice. This review’s aim was to provide a broad overview of the current state of research regarding the effects of seven commonly used motor learning strategies to improve functional tasks within older neurological and geriatric populations.

Method

A systematic mapping review of randomised controlled trials was conducted regarding the effectiveness of seven motor learning strategies – errorless learning, analogy learning, observational learning, trial-and-error learning, dual-task learning, discovery learning, and movement imagery – within the geriatric and neurological population. PubMed, CINAHL, and Embase databases were searched. The Risk of Bias 2 tool was used to assess bias; additionally, papers underwent screening for sample size justification.

Results

Eighty-seven articles were included. Identified articles regarding the effects of the targeted motor learning strategies started around the year 2000 and mainly emerged since 2010. Eight different populations were included, e.g. Parkinson’s, and stroke. Studies were not equally balanced across the motor learning strategies or target groups and overall showed a moderate to high risk of bias. Positive trends regarding effects were observed for dual-tasking, observational learning and movement imagery.

Conclusions

The findings show a skewed distribution of studies across motor learning interventions, which have been researched within a variety of populations. Methodological shortcomings make it difficult to draw firm conclusions regarding the effectiveness of motor learning strategies. Future researchers are strongly advised to follow guidelines that aid in maintaining methodological quality. Moreover, alternative designs fitting the complex practice situation should be considered.