bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of acupressure, laughter yoga, and a mindfulness-based stress reduction program applied to postmenopausal women for menopause symptoms and quality of life
Authors: Koca Hacer U. , Kucukkelepce Didem S. , Nacar Gulcin , Çetin Nurdilan S. , Taşhan Sermin T.
Published: September 2024

Objective

This research was conducted to determine the effects of acupressure, laughter yoga, and a mindfulness-based stress reduction program applied to postmenopausal women for menopause symptoms and quality of life.

Methods

A randomized controlled design was used. The study was conducted with a total of 146 women, including 41 acupressure, 31 laughter yoga, 37 mindfulness-based stress reduction, and 37 control group women. The women in the acupressure group were administered acupressure twice a week, which accounted for 16 sessions in total. Women in the laughter yoga and mindfulness-based stress reduction groups received a total of eight sessions of the related intervention, which was performed once a week. Study data were collected using a participant information form, the Menopause Rating Scale (MRS), and the Menopause-Specific Quality of Life Scale (MENQOL). Descriptive statistics, paired-samples t test, χ2 test, analysis of variance test, and intention to treat analysis were used to analyze the data. Before the intention to treat analysis was performed, the multiple imputation method was employed to deal with missing data.

Results

In the study, it was found that there was a decrease in the MRS total score after the intervention in women in all three intervention groups compared to the control group (P < 0.05). In the laughter yoga group, total MRS scores decreased by 3.16 points (P < 0.05). In the acupressure group, total MRS scores decreased by 5.46 points (P < 0.05). In the mindfulness-based stress reduction (MBSR) program group, total MRS scores decreased by 4.65 points (P < 0.05). It was determined that the mean scores of women in the laughter yoga and acupressure groups on all subscales of the MENQOL decreased after the intervention compared to the control group (P < 0.05). The comparison of the MBSR group and the control group showed that there was a decrease only in the psychosocial domain subdimension of the MENQOL (P < 0.05).

Conclusions

In conclusion, it was determined that laughter yoga, acupressure, and MBSR could be effective in reducing menopause symptoms and improving quality of life, although findings require further testing in a rigorously controlled study and in a study with only a single prespecified outcome.
Analysis of the Radial Forearm Phalloplasty Donor Site: Do Dermal Matrices Improve Donor Site Morbidity?
Authors: Marquez Jessica L. , Nuckles Brandon , Tausinga Telisha , Foley Brittany , Sudbury Dallin , Sueoka Stephanie , Zang Chong , Lewis Priya , Goodwin Isak
Published: September 2024

Background:

The radial forearm free flap is frequently chosen for phalloplasty; however, flap size required for phalloplasty is associated with a large scar burden and functional concerns. We sought to investigate donor site functionality, aesthetics, and volume deficits in a cohort of individuals who underwent radial forearm phalloplasty (RFP) with donor site skin grafting alone or dermal substitute and subsequent skin grafting.

Methods:

Donor site functionality was assessed using the quick Disabilities of Arm, Shoulder, and Hand (qDASH). Patient- and clinician-reported aesthetics were assessed using the Patient and Observer Scar Assessment Scale (POSAS). An Artec Leo three-dimensional scanner was used to measure volumetric differences from the donor site forearm and contralateral forearm.

Results:

Fifteen patients who underwent RFP agreed to participate. No statistically significant differences were identified between different donor site closure methods regarding qDASH, patient-reported POSAS, or total volumetric deficits. A blinded clinician reported that POSAS approached significance at 4.7 for biodegradable temporizing matrix (BTM), 4.2 for Integra, and 3.0 for split-thickness skin graft (P = 0.05). No statistically significant differences were identified regarding distal, middle, or proximal volume deficits; however, a trend was observed regarding total volumetric deficits with BTM experiencing the lowest deficit (10.3 cm3) and skin graft experiencing the highest deficit (21.5 cm3, P = 0.82).

Conclusions:

The addition of dermal matrix (BTM or Integra) to the treatment algorithm for RFP did not show statistically significant improvement in donor site volume deficits, patient-reported scar appearance (POSAS), or functionality (qDASH).
A Multicenter Validation of a Novel Prediction Model for Elbow Flexion Recovery after Nerve Transfer Surgery in Brachial Plexus Injuries
Authors: Laohaprasitiporn Panai , Kittithamvongs Piyabuth , Monteerarat Yuwarat , Suriyarak Theerawat , Siripoonyothai Sopinun , Neti Nutdanai
Published: September 2024

Background:

Nerve transfer surgery for brachial plexus injuries exhibits variable success rates, potentially resulting in prolonged limb dysfunction for more than 2 years. A proposed prediction model has been developed to predict the unsuccessful recovery of elbow flexion after the surgery. The model consisted of six variables, namely body mass index 23 kg/m2 or more, smoking, total arm type, donor nerve, ipsilateral upper extremity fracture, and ipsilateral vascular injury. This study aimed to assess the external validity of the model for wider applicability.

Methods:

This retrospective analysis examined the medical records of 213 eligible patients with traumatic brachial plexus injuries who underwent surgery at two referral centers between July 2008 and June 2022. The prediction model was applied to estimate recovery failure probability, which was compared with the observed outcomes for each patient. Both the original and simplified models were validated for discrimination and calibration using metrics including c-statistic, Hosmer–Lemeshow goodness-of-fit test, calibration plot, calibration slope, and intercept.

Results:

Thirty-two percent of patients experienced unsuccessful elbow flexion recovery. Both the original and simplified models demonstrated good discrimination (c-statistics: 0.748 and 0.759, respectively). The Hosmer–Lemeshow test revealed strong agreement between predicted and observed probabilities for both models (P = 0.66 and P = 0.92, respectively). The calibration plot exhibited good agreement, with a calibration slope of 0.928 and an intercept of 0.377.

Conclusions:

The prediction model showed strong external validation, confirming its clinical value. High-risk patients should be educated on the risks and benefits of nerve transfer surgery and consider alternative treatments such as primary free functioning muscle transfer.
Innovating Flexor Tendon Repair Training with a Three-dimensional Printed Model
Authors: Boyajian Michael K. , Davidson Amelia L. , Molair Will , Woo Albert S. , Crozier Joseph W. , Johnson James E. , Bhatt Reena , Danelson Kerry A. , Argenta Anne
Published: September 2024

Background:

Flexor tendon repair is a technically demanding procedure, with functional outcome directly proportional to skillful execution. A repair must be strong to manage early mobilization and precise to allow for gliding through the tendon sheath. As a result, junior residents face a steep learning curve that may be mitigated by exposure to surgical simulators.

Methods:

To facilitate flexor tendon repair training, a surgical training device and accompanying instructional video were developed. Simulation workshops were held for junior orthopedic and plastic surgery residents (n = 11). To objectively assess validity of the curriculum, study participants performed cadaveric flexor tendon repairs before and after the workshop. Anonymous recordings of these repairs were graded by two certified hand surgeons. Additionally, a tensometer was used to measure strength of repair.

Results:

Model realism, educational utility, and overall usefulness rated high: 4.6 ± 0.52 95% confidence interval (CI) for realism, 4.9 ± 0.42 95% CI for device, 4.7 ± 0.96 95% CI for video, and 4.9 ± 0.66 95% CI overall. Subjective confidence increased after the training session (73% ranked “moderately” or “extremely”). Likewise, scores given by the surgeons grading the repairs improved for overall quality and time of repair (pre: 2.77 ± 0.61, post: 4.22 ± 0.56, P= 0.0002). Strength of repair did not change (P = 0.87).

Conclusions:

The proposed three-dimensional surgical simulator for flexor tendon repair is realistic and useful, with improved surgical technique and improved confidence demonstrated after use. This design can be three-dimensionally printed en masse and provide value to hand surgery training curriculum.
Effect of Masking Secondary to the COVID-19 Pandemic on Functional Capacity Improvement in Cardiac Rehabilitation
Authors: Lu Frederick , Berkowitz Julia , Gaw Arlene , Salvador Vincent , DeAngelis Julianne , Wu Wen-Chih
Published: September 2024

Purpose:

Given the difficulty to perform exercise training wearing a mask, we examined differences in functional capacity improvement between masking during the coronavirus disease 2019 (COVID-19) pandemic and non-masking prior to the pandemic for patients undergoing cardiac rehabilitation (CR).

Methods:

Records of 660 patients who underwent and completed ≥ 18 sessions of CR in 2018 (n = 318, non-masking) and in 2022 (n = 342, masking) at an academic health system were analyzed. The primary outcome was post-CR change in functional capacity in metabolic equivalents (MET) measured by exercise stress test. Sessions of CR participation and changes in depression, anxiety, and quality of life scores were secondary outcomes. We used multivariable linear regression to adjust for differences in baseline CR outcome measures, demographics, American Association of Cardiovascular and Pulmonary Rehabilitation (AACVPR) risk, and comorbid conditions.

Results:

Baseline age (64.6 ± 0.46 yr), sex (28% female), and racial distribution (85% white) were similar between the masking and non-masking groups. Non-masking patients were more likely to be classified in the AACVPR high risk category and had lower anxiety scores at baseline compared to masking patients. After CR, both groups had similar and significant improvements in depression, anxiety, and quality of life scores, but the improvement in functional capacity was lower in the masking group (−0.62 ± 0.12 MET, P < .001) compared to the non-masking group. Results remained significant after multivariable adjustment.

Conclusions:

Cardiac rehabilitation patients requiring masking during the COVID-19 pandemic had less improvement in functional capacity than patients who did not wear masks during CR prior to the pandemic. Interventions to mitigate the potential side effects of masking for CR patients may require further exploration.
Immunobiology of primary sclerosing cholangitis
Authors: Cornillet Martin , Geanon Daniel , Bergquist Annika , Björkström Niklas K.
Published: September 2024

Primary sclerosing cholangitis (PSC) is a chronic inflammatory progressive cholestatic liver disease. Genetic risk factors, the presence of autoantibodies, the strong clinical link with inflammatory bowel disease, and associations with other autoimmune disorders all suggest a pivotal role for the immune system in PSC pathogenesis. In this review, we provide a comprehensive overview of recent immunobiology insights in PSC. A particular emphasis is given to immunological concepts such as tissue residency and knowledge gained from novel technologies, including single-cell RNA sequencing and spatial transcriptomics. This review of the immunobiological landscape of PSC covers major immune cell types known to be enriched in PSC-diseased livers as well as recently described cell types whose biliary localization and contribution to PSC immunopathogenesis remain incompletely described. Finally, we emphasize the importance of time and space in relation to PSC heterogeneity as a key consideration for future studies interrogating the role of the immune system in PSC.
Implementation of a Nurse-Initiated Protocol to Improve Enteral Medication Administration Documentation in Stroke Patients
Authors: Drennan John C. , Sheehan Tiffany O. , Schroeder Tracie , Haller J. Tyler
Published: September 2024

BACKGROUND: Medication documentation falls under the “7 rights” of medication administration, but strategies to prevent medication administration documentation errors (MADEs) related to route of administration are underreported in the literature. This study aimed to report the outcomes of a nurse-initiated protocol designed to prevent MADEs and align both actual and documented medication administration routes in hospitalized stroke patients with feeding tubes (FTs). METHODS: This was a retrospective descriptive study conducted at a Comprehensive Stroke Center and large academic medical center in the Western United States. Adults admitted with the diagnosis of stroke between February 2022 and August 2023, who had an FT on arrival, or placed during admission, and received at least 1 enteral medication ordered for by mouth (PO) administration, were included. The protocol allowed nurses to place a communication order to a pharmacist via the electronic health record, requesting all enteral medications ordered for PO administration be changed to FT administration. RESULTS: There were 481 patients included with a median age of 68 years (interquartile range, 58–76 years). The nurse-initiated protocol was used in 170 patients (35.3%), with 99 patients (58.2%) having all enteral medication orders converted completely by a pharmacist. Of the 170 patients in which the protocol was initiated, 145 (85.3%) had all scheduled enteral medication orders converted. For the 71 patients who did not have all enteral medication orders converted completely, the median number of potential MADEs was 2 (1–4.5). CONCLUSION: A nurse-initiated protocol designed to prevent MADEs and improve the accuracy of actual and documented route of medication administration for patients hospitalized for stroke with FTs had modest use. The nurse-initiated protocol in this study is the first of its kind and may help guide further research on preventing and reducing MADEs.
Family Caregivers' Experiences of People With Amyotrophic Lateral Sclerosis Undergoing Gastrostomy Tube Feeding
Authors: Chu Hyeon Sik , Oh Juyeon
Published: September 2024

INTRODUCTION: In amyotrophic lateral sclerosis (ALS) patients with impaired swallowing function, gastrostomy tube (G-tube) placement is recommended, but significantly increases the caregiving burden on families. This study aimed to describe the experiences of family caregivers of patients with ALS receiving home enteral nutrition through a G-tube. METHOD: Using purposive sampling, 8 family caregivers participated in the study. Data collection was conducted between February 2021 and October 2022 at a university hospital in Seoul, Korea. Semistructured face-to-face interviews were used to collect data until saturation. Data were analyzed using Krippendorff's content analysis approach. RESULTS: Qualitative analysis of the data revealed 3 main themes regarding caregiving. The emerging themes included psychological distress, unmet practical needs, and the struggle to provide care. CONCLUSION: After a G-tube placement, family caregivers experience various emotional stresses and have numerous unmet practical needs. Healthcare professionals caring for people with ALS receiving enteral nutrition should provide a tailored support program that addresses the specific needs of these family caregivers.
Safety of acamprosate for alcohol use disorder after liver transplant: A pilot randomized controlled trial
Authors: Ayyala-Somayajula Divya , Bottyan Thomas , Shaikh Suhail , Lee Brian P. , Cho Stephanie H. , Dodge Jennifer L. , Terrault Norah A. , Han Hyosun
Published: September 2024

Acamprosate is a therapy for alcohol use disorder, but data on feasibility and safety in recipients of liver transplants are lacking. This was a single-center unblinded prospective pilot randomized controlled trial of adults (≥18 y) with liver transplant for alcohol-associated liver disease enrolled between 2021 and 2023, who were randomized 2:1 to the intervention of acamprosate (666 mg dose 3 times daily) or standard of care (SOC) over 14 weeks. Outcomes included safety (prevalence of adverse events [AEs]), feasibility (weekly survey response rate >60%), adherence (self-reported acamprosate use >60%), and efficacy (reduction in Penn Alcohol Craving Scale), and relapse-blood phosphatidylethanol (≥20 ng/mL/reported alcohol use) evaluated by standardized weekly surveys. The efficacy analysis was done in both the intention-to-treat (excluding withdrawals before medication administration) and per-protocol population (excluding withdrawals/<4 weeks participation). Of 78 participants who were approached, 30 enrolled (19 acamprosate and 11 SOC) with similar baseline characteristics. Eight participants withdrew (6 acamprosate before medication administration and 2 SOC). AEs were similar between acamprosate and SOC groups (92.3% vs. 90.0%, p > 0.99), including grade 3 AEs (53.9% vs. 60.0%, p > 0.99) with no reported grade 4/5 AEs. Survey response rates were similar in acamprosate versus SOC groups (61.0% vs. 76.0%, p = 0.19), and 69.0% were acamprosate adherents. Baseline Penn Alcohol Craving Scale values were low with no difference by the group in median absolute change in Penn Alcohol Craving Scale for intention-to-treat (0, IQR: −4 to 0 vs. 0, IQR: 0–0, p = 0.32), and per-protocol analyses (−1, IQR: −6 to 0 vs. 0, IQR: −0 to 0, p = 0.36). There was no reported or biochemical evidence of alcohol relapse. In this pilot study, preliminary data suggest that acamprosate may be safe and feasible. These data can inform larger studies and clinician efforts to address alcohol use disorder in post-liver transplant care (ClinicalTrials.gov, Number: NCT06471686).
What’s Behind it all: A Retrospective Cohort Study of Retrogastric Pancreatic Necrosis Management
Authors: Harrison Jon M , Day Heather , Arnow Katherine , Ngongoni R. Fari , Joseph Abel , Aldridge Taylor , Wheeler Kristan J , DeLong Jon C , Bergquist Jay R , Worth Patrick J , Dua Monica M , Friedland Shai , Park Walter , Eldika Samer , Hwang Joo Ha , Visser Brendan C
Published: September 2024

Objective:

To compare outcomes of laparoscopic transgastric necrosectomy (LTN) and direct endoscopic necrosectomy (DEN) in the management of retrogastric walled-off necrosis.

Summary of Background Data:

Surgical and endoscopic transgastric approaches are used to manage retrogastric pancreatic necrosis. Studies comparing these treatment modalities are lacking but would influence contemporary practice patterns.

Methods:

LTN or DEN treated patients at Stanford University Hospital between 2011 and 2023 were identified. Cohort data included demographics, core pancreatitis care benchmarks, and clinical outcomes (total debridement time, new-onset endocrine and exocrine pancreatic insufficiency) as well as re-intervention, 30-day readmission, complication, and mortality rates. Long-term follow-up was also compared between intervention arms. Multivariable linear regression was used to assess the interaction between admission APACHE-II score and intervention on length of stay (LOS).

Results:

106 patients (62% LTN, 38% DEN) were identified. Demographic and core pancreatitis benchmark data were similar between cohorts. 30-day readmission, complication, and mortality rates for surgical and endoscopic approaches were also similar: 23% vs. 25% (P = 0.98), 42% vs. 40% (P = 0.97), and 3% vs. 3% (P > 0.99). Median LTN total debridement time (minutes) was 131 vs. 134 for DEN, however, complete debridement was achieved with only 1 LTN compared to 3 DENs (P<0.01). While not statistically significant, LOS and unplanned intervention rates were less for LTN (8 vs. 10 days, P = 0.41 and 6% vs. 15%, P = 0.24). Multivariable analysis revealed a significant interaction between APACHE-II scores and LOS for LTN compared to DEN, which translated into a length of stay reduction for higher APACHE-II scoring patients (P = 0.02).

Conclusions:

LTN is a safe and efficient treatment modality for walled-off necrosis, and compared to DEN, can reduce the LOS in high APACHE-II score patients. While additional comparative research between the two intervention types is needed, this study supports a role for a surgical approach in the management of retrogastric pancreatic necrosis.
Mid-term Waitlist and Posttransplant Outcomes With Hepatitis C-positive Donor Hearts
Authors: Hong Yeahwa , Couper Caitlin D. , Iyanna Nidhi , Hess Nicholas R. , Ziegler Luke A. , Abdullah Mohamed , Mathier Michael A. , Hickey Gavin W. , Keebler Mary E. , Silvestry Scott C. , Kaczorowski David
Published: September 2024

Background.

This study evaluates the clinical trends and impact of hepatitis C virus-positive (HCV+) donors on waitlist and posttransplant outcomes after heart transplantation.

Methods.

The United Network for Organ Sharing registry was queried to identify adult waitlisted and transplanted patients from January 1, 2015, to December 31, 2022. In the waitlist analysis, the candidates were stratified into 2 cohorts based on whether they were willing to accept HCV+ donor offers. Waitlist outcomes included 1-y cumulative incidences of transplantation and death/delisting. In the posttransplant analysis, the recipients were stratified into 2 cohorts with and without HCV nucleic acid test (NAT)-positive donors. Outcomes included 1- and 4-y posttransplant survival. Propensity score-matching was performed. Risk adjustment was performed using multivariable Cox regression.

Results.

During the study period, the number of centers using HCV NAT+ donors increased from 1 to 65 centers, along with the number of transplants. In the waitlist analysis, 26 648 waitlisted candidates were analyzed, and 4535 candidates (17%) were approved to accept HCV+ donors. Approval to accept HCV+ donors was associated with a higher likelihood of transplantation and a lower likelihood of death/delisting within 1 y of waitlisting. In the posttransplant analysis, 21 131 recipients were analyzed, and 997 recipients (4.7%) received HCV NAT+ hearts. The 1- and 4-y posttransplant survival were comparable between the recipients of HCV NAT+ and NAT− donors. Furthermore, the similar 1- and 4-y posttransplant survival persisted in the propensity score-matched comparison and multivariable Cox regression analysis.

Conclusions.

Utilization of HCV+ donors is rising. Heart transplants using HCV+ donors are associated with improved waitlist and comparable posttransplant outcomes.
Genomic insights into indole-3-acetic acid catabolism in the marine algae-associated bacterium, Marinomonas sp. NFXS50
Authors: Bertrand Constança , Martins Rodrigo , Nunes Francisco , Brandão Pedro , Nascimento Francisco X.
Published: September 2024

Auxins, mainly in the form of indole-3-acetic acid (IAA), regulate several aspects of plant and algal growth and development. Consequently, plant and algae-associated bacteria developed the ability to modulate IAA levels, including IAA catabolism. In this work, we present and analyse the genome sequence of the IAA-degrading and marine algae-associated bacterium, Marinomonas sp. NFXS50, analyse its IAA catabolism gene cluster and study the prevalence of IAA catabolism genes in other Marinomonas genomes. Our findings revealed the presence of homologs of the Pseudomonas iac gene cluster, implicated in IAA catabolism, in the genome of strain NFXS50; however, differences were observed in the content and organization of the Marinomonas iac gene cluster when compared to that of the model iac-containing Pseudomonas putida 1290. These variations suggest potential adaptations in the IAA catabolism pathway, possibly influenced by substrate availability and evolutionary factors. The prevalence of iac genes across several Marinomonas species underscores the significance of IAA catabolism in marine environments, potentially influencing plant/algae-bacteria interactions. This study provides novel insights into the IAA catabolism in Marinomonas, laying the groundwork for future investigations into the role of iac genes in Marinomonas physiology and the regulation of marine plant/algae-bacteria interactions.
Mutations in the efflux regulator gene oqxR provide a simple genetic switch for antimicrobial resistance in Klebsiella pneumoniae
Authors: Dawson Catherine J. , Bartczak Amelia , Hassan Karl A.
Published: September 2024

Klebsiella pneumoniae is a pathogen of major concern in the global rise of antimicrobial resistance and has been implicated as a reservoir for the transfer of resistance genes between species. The upregulation of efflux pumps is a particularly concerning mechanism of resistance acquisition as, in many instances, a single point mutation can simultaneously provide resistance to a range of antimicrobials and biocides. The current study investigated mutations in oqxR, which encodes a negative regulator of the RND-family efflux pump genes, oqxAB, natively found in the chromosome of K. pneumoniae. Resistant mutants in four K. pneumoniae strains (KP6870155, NTUH-K2044, SGH10, and ATCC43816) were selected from single exposures to 30 µg/mL chloramphenicol and 12 mutants were selected for whole genome sequencing to identify mutations associated with resistance. Resistant mutants generated by single exposures to chloramphenicol, tetracycline, or ciprofloxacin at ≥4 X MIC were replica plated onto all three antibiotics to observe simultaneous cross-resistance to all compounds, indicative of a multidrug resistance phenotype. A variety of novel mutations, including single point mutations, deletions, and insertions, were found to disrupt oqxR leading to significant and simultaneous increases in resistance to chloramphenicol, tetracycline, and ciprofloxacin. The oqxAB-oqxR locus has been mobilized and dispersed on plasmids in many Enterobacteriaceae species and the diversity of these loci was examined to evaluate the evolutionary pressures acting on these genes. Comparison of the promoter regions of oqxR in plasmid-borne copies of the oqxR-oqxAB operon indicated that some constructs may produce truncated versions of the oqxR transcript, which may impact on oqxAB regulation and expression. In some instances, co-carriage of chromosomal and plasmid encoded oqxAB-oqxR was found in K. pneumoniae, implying that there is selective pressure to maintain and expand the efflux pump. Given that OqxR is a repressor of oqxAB, any mutation affecting its expression or function can lead to multidrug resistance. This is in contrast to antibiotic target site mutations that must occur in limited sequence space to be effective and not impact the fitness of the cell. Therefore, oqxR may act as a simple genetic switch to facilitate resistance via OqxAB mediated efflux.
The Impact of COVID-19 Lockdowns on Mental Health: A Comparative Study
Authors: Orgad Kfir
Published: September 2024

The COVID-19 pandemic led to unprecedented global lockdowns aimed at controlling the spread of the virus. While effective in reducing transmission, these lockdowns have had significant repercussions on mental health. This study examines the prevalence and incidence of mental health problems during the COVID-19 lockdowns, comparing countries that implemented strict lockdown measures with those that did not. Using statistical analysis, we demonstrate that lockdowns are associated with a statistically significant increase in mental health issues. These findings suggest that public health policies during pandemics must balance the physical and mental health needs of the population.
Subunit-specific conductance of single HCN pacemaker channels at femtosiemens resolution
Authors: Benndorf Klaus , Enke Uta , Tewari Debanjan , Kusch Jana , Liu Haoran , Sun Han , Schmauder Ralf , Sattler Christian
Published: September 2024

Hyperpolarization-activated cyclic nucleotide-modulated (HCN) channels are tetramers that generate rhythmic electrical activity in neuronal and cardiac pacemaker cells1. The channels are activated by hyperpolarisation of the membrane voltage and additionally tuned by the second messenger cAMP at sympathetic stimulation. There are four mammalian isoforms, HCN1-42–4. The single-channel conductance,γ, of HCN channels remains debated, with conflicting results ranging from near 1.5 pS for HCN25,6to tens of pS for HCN17, HCN27and HCN47,8, though the pore structure, viewed to determine the conductance9,10, is either identical or highly conserved. To resolve this controversy, we analyzed all four mouse isoforms mHCN1-4 at femtosiemens resolution. We show that mHCN1, mHCN3 and mHCN4 also generate small conductance values, even smaller than that of mHCN2 with the sequenceγmHCN2=1.54 pS >γmHCN1=0.84 pS >γmHCN3=0.54 pS ≍γmHCN4=0.51 pS. As shown by systematic mutagenesis and molecular dynamic simulations, the differences in the conductance are neither generated by the selectivity filter nor the inner gate9, but by defined negative charges in the outer channel vestibule increasing cation occupation. In line with these results, heteromers of mHCN2 with either mHCN1, mHCN3 or mHCN4 lead to graded single-channel currents in-between those of the respective homomeric channels. Our approach at femtosiemens resolution provides insight into the function of recombinant and native HCN channels at the level of single subunits and is thus promising for the development of subunit-specific drugs acting on these clinically highly relevant channels11.
Systematic Review on the Role of Microbial Activities on Nutrient Cycling and Transformation Implication for Soil Fertility and Crop Productivity
Authors: Bayu Tesfaye
Published: September 2024

Soil microorganisms play a vital role in the regulation of the transformation and cycle of soil nutrients, thereby improving soil fertility and crop productivity. These microbes, associated with plants, contribute significantly to plant growth and development by improving nutrient cycling and crop productivity by improving soil fertility. This systematic review aims to assess the impact of microbial activity on nutrient cycle and transformation, which includes soil fertility and crop productivity improvement. The PRISMA flow methodology systematically included articles from various geographic regions. Through analyzing 120 articles, this review sought to address the question at hand. Among the articles analyzed, 31.4% indicate that soil microbial activity directly regulates nutrient cycling, while 68.6% suggest that microbial activity enhances soil fertility and crop productivity. The systematic review concludes that microbial activity has a significant effect on nutrient cycle and transformation, as well as on improving soil fertility and crop productivity. Farmers, policymakers, and experts are encouraged to manage soil microorganisms to regulate nutrient cycling, directly influencing soil fertility and crop productivity, thus promoting sustainable agricultural development.
PREVALENCE AND TREATMENT OUTCOME OF ANORECTAL MALFORMATION AT MNAZI MMOJA REFERRAL HOSPITAL 2018-2022
Authors: Chongera Ahmad Moshi , Ally Abdulkarim Hamad , Mussa Mwanakhamis Vuai , Mnyaruge Yasinta Edison , Said Said A , Haji Mwanabaraka Saleh
Published: September 2024

BACKGROUND

Anorectal Malformations (ARM) are congenital defects where the anus and rectum do not form correctly, presenting a range of complexities that often necessitate intricate surgical interventionist global incidence of ARM is approximately 1 in 2000 to 5000 live births. In developing countries like Tanzania, managing ARMs poses significant challenges due to late presentations, shortage of trained pediatric surgeons and inadequate diagnostic facilities. This study aimed to evaluate the prevalence and treatment outcomes of ARM at Mnazi Mmoja Hospital (MMH) over five years 2018 to 2022

OBJECTIVES

including analyzing patient demographics (age and sex), the prevalence of ARMs, common types, surgical procedure used and associated complications. A retrospective, descriptive cross-sectional study was conducted using data from structed questionnaire, which were analyzed with SPSS software.

RESULTS

revealed that the sex distribution of patients was nearly equal, with ARM cases increasing from 8 (9.9%) in 2018 to 33(40.7%) in 2022. The majority of cases were in Urban Wes (49.9%), and most patients (90.1%) had major ARMs. Surgical treatments included three-stage procedures (65.4%) and one-stage procedures (13.6%), with a postoperative complication rate of 17.2%. survival was high, with 90.1% survival rate and low mortality rate of 9.9%

CONCLUSION

ARM remains a prevalent and challenging surgical issue in Zanzibar, constituting 35% 0f pediatric gastrointestinal surgeries. Implementing modern single-stage surgical approaches could potentially improve patient outcomes and reduces complications
Safety During Night Duty: Survey of 3885 Doctors Across India
Authors: Jayadevan Rajeev , Augustine Deepa , Anithadevi TS , Ramachandran Reshmi , Benaven Joseph
Published: September 2024

Background

Reports of violence against doctors at the workplace are on the rise. In August 2024, a young female doctor was raped and murdered during night duty at her workplace in Kolkata, India. This incident prompted nationwide protests and a service shutdown by doctors’ organizations advocating for improved workplace safety.

Aim

This survey was undertaken by the Indian Medical Association to evaluate safety concerns during night shifts among doctors. With 3,885 individual responses, it is the largest study from India on this topic.

Methods

An online survey was sent to doctors across India through a Google form. There were 3885 responses within 24 hours. In addition to seeking suggestions to improve safety, three separate parameters were assessed:

0-10 numeric rating scale of perception of safety

Availability of duty room

Access to bathroom while on night duty

Results

Respondents were from several states. 85% were under 35 years. 61% were interns or postgraduate trainees. Women constituted 63%, aligning with the gender ratio in some MBBS courses.

Several doctors reported feeling unsafe (24.1%) or very unsafe (11.4%), totalling one-third of the respondents. The proportion of those feeling unsafe was higher among women.

A duty room was not available to 45% of respondents during night shifts.

Those with access to a duty room had greater sense of safety.

Duty rooms were often inadequate due to overcrowding, lack of privacy and missing locks, forcing doctors to find alternative rest areas.

One-third of available duty rooms did not have an attached bathroom.

In more than half the instances (53%), duty room was located far from the ward/casualty area.

Suggestions to enhance safety included increasing the number of trained security personnel, installing CCTV cameras, ensuring proper lighting, implementing the Central Protection Act (CPA), restricting bystander numbers, installing alarm systems, and providing basic amenities such as secure duty rooms with locks. For detailed information, refer to Table 13, the synopsis and the verbatim comments section.

Conclusions

Doctors across the country, particularly women, report feeling unsafe during night shifts. There is substantial scope for improving security personnel and equipment in healthcare settings. Modifications to infrastructure are essential to ensure safe, clean, and accessible duty rooms, bathrooms, food, and drinking water. Adequate staffing, effective triaging, and crowd control in patient care areas are also necessary to ensure that doctors can provide the required attention to each patient without feeling threatened by their work environment.
Impacts of Global School Feeding Programmes on Children’s Health and Wellbeing Outcomes: A Scoping Review
Authors: Locke Amy , James Michaela , Jones Hope , Davies Rachel , Williams Francesca , Brophy Sinead
Published: September 2024

Background

School feeding programmes (SFP) are one of the world’s most extensive interventions to alleviate child poverty, food insecurity and malnutrition. Schools are ideal settings to promote healthy eating habits early in life since children have access to at least one main meal per day at school. However, there is a lack of clear evidence for the effectiveness of school feeding programmes on child health outcomes. Additionally, there is considerable debate on whether feeding programmes should be universal or targeted with countries taking different approaches. This review will therefore explore global research on school feeding programmes and consider different health outcomes through targeted or universal policies.

Methods

We conducted a search across four electronic databases. These studies investigated the impacts of school feeding programmes on children’s health outcomes. 207 papers were identified with 76 studies subjected to full text screening.

Results

A total of 42 papers were included in the final review. All papers were published within the past fifteen years (2009-2024) and included thirteen countries in total. SFP were associated with child weight being more in the healthy range. Targeted SFP were negatively associated with stigma.

Conclusions

Universal SFP were effective at improving children’s health outcomes such as healthy weight, improved behaviour and social support. Overall, both targeted and universal SFP positively impact children’s health outcomes and address health disparities.

STRENGTHS AND LIMITATIONS OF THIS STUDY

The review mapped both universal and targeted provisions, providing a broad overview of the existing literature.

The review included an appraisal of the methodological quality of the included studies. Only English studies were included.

Only studies published in English were included, potentially excluding relevant research in other languages.

The study did not perform a formal assessment of publication bias, which could impact the interpretation of the results.
Hypothalamic structure and function in Alzheimer’s disease and Lewy-body dementia: a systematic review and meta-analysis
Authors: Laurell Axel AS , Shah Sita N , Rahmati Masoud , O’Brien John T , Underwood Benjamin R
Published: September 2024

Background

Changes to sleep, weight, and endocrine function are common in Alzheimer’s disease (AD) and Lewy-body dementia (LBD). The cause of these is not known, but they may be related to hypothalamic neurodegeneration.

Methods

We performed a systematic search of MEDLINE and EMBASE of studies using structural magnetic resonance imaging to examine hypothalamic volume in people with AD or LBD. The Newcastle-Ottawa scale was used to assess the risk of bias. A random-effects meta-analysis was conducted using the standardised mean difference (SMD) in hypothalamic volume as the effect measure, and a narrative synthesis was used to examine the relationship between hypothalamic volume and sleep, eating, and endocrine function.

Results

We identified 6542 articles which resulted in 12 included studies, most which had a low to moderate risk of bias. The meta-analysis included 454 people with mild-moderate AD (Mini-Mental State (MMSE) range: 19.2-26.1) and 715 controls. We found that people with AD had a significantly smaller hypothalamus (pooled SMD: -0.49, t=-3.47, p=0.018, 95%CI: -0.86 to - 0.13). There was significant heterogeneity of a moderate degree (Tau2=0.0665, 95%CI:0.005-0.8090; I2=67%, 95%CI:21.5%-86.1%; Q=15.16, p<0.01), but no evidence of publication bias. Only one study examined people with LBD, finding qualitative evidence of lower hypothalamic volume compared to controls. Hypothalamic volume loss in AD was more marked in men and may be associated with plasma levels of sex hormones and decreased bone mineral density.

Conclusion

Reduced hypothalamic volume is seen early in AD and LBD and this may influence endocrine function. A better understanding of hypothalamic degeneration in dementia may help elucidate how pathology relates to symptoms in AD and LBD and reveal new targets for intervention.
From impact metrics and open science to communicating research: Journalists’ awareness of academic controversies
Authors: Fleerackers Alice , Moorhead Laura L. , Alperin Juan Pablo , Riedlinger Michelle , Maggio Lauren A.
Published: September 2024

This study sheds light on how journalists respond to evolving debates within academia around topics including research integrity, improper use of metrics to measure research quality and impact, and the risks and benefits of the open science movement. Drawing on semi-structured interviews with 19 health and science journalists, we describe journalists’ awareness of these controversies and the ways in which that awareness, in turn, shapes the practices they use to select, verify, and communicate research. Our findings suggest that journalists’ perceptions of debates in scholarly communication vary widely, with some displaying a highly critical and nuanced understanding and others presenting a more limited awareness. Those with a more in-depth understanding report closely scrutinizing the research they report, carefully vetting the study design, methodology, and analyses. Those with a more limited awareness are more trusting of the peer review system as a quality control system and more willing to rely on researchers when determining what research to report on and how to vet and frame it. We discuss the benefits and risks of these varied perceptions and practices, highlighting the implications for the nature of the research media coverage that reaches the public.
Short-term memory errors are strongly associated with a drift in neural activity in the posterior parietal cortex
Authors: Choi Joon Ho , Bae Sungwon , Park Jiho , Yoo Minsu , Kim Chul Hoon , Schmitt Lukas Ian , Choi Ji-Woong , Rah Jong-Cheol
Published: September 2024

Understanding the neural mechanisms behind short-term memory (STM) errors is crucial for unraveling cognitive processes and addressing related deficits in neuropsychiatric disorders. This study investigates whether STM errors result from misrepresentation of sensory information or a decay in these representations over time. Utilizing 2-photon calcium imaging in the posterior parietal cortex (PPC) of mice engaged in a delayed match-to-sample task, we identified a subset of PPC neurons exhibiting both directional and temporal selectivity. Contrary to the idea that STM errors primarily stem from mis-encoding during the sample phase, our findings indicate that these errors are more closely associated with a drift in neural activity during the delay period. This drift results in a gradual shift away from the correct representation, ultimately leading to incorrect behavioral responses. These results emphasize the importance of maintaining stable neural representations in the PPC for accurate STM. Our findings also suggest that targeting PPC activity stabilization during delay periods could be a potential therapeutic strategy for mitigating cognitive impairments in disorders like schizophrenia.
Temporal proteomic and PTMomic atlas of cerebral organoid development
Authors: Elmkvist Sofie B. , Bogetofte Helle , Jensen Pia , Jakobsen Lene A. , Havelund Jesper F. , Ryding Matias , Brewer Jonathan , Færgeman Nils J. , Lancaster Madeline A. , Larsen Martin R.
Published: September 2024

Cerebral organoids (CBOs) are generated from pluripotent stem cells that undergo neuroectoderm specification and neuronal differentiation in three dimensions. The developing neurons in CBOs migrate and self-organize into cerebral cortex-like layers, mimicking human brain development. CBOs develop according to intrinsic signaling mechanisms and offer unique insights into mechanisms of early human brain development. This process requires coordinated spatiotemporal regulation of protein expression and function, where the latter can be achieved by post-translational modifications (PTMs) on proteins. Despite the importance of proteins in brain development and function, profiling of protein abundance and the involvement of PTMs in CBO development remain underexplored. To gain insight into protein and PTM abundance in CBOs, we performed a high-resolution temporal analysis of CBOs up to day 200 using proteomics, PTMomics and metabolomics. We quantified more than 9,300 proteins and various neurodevelopmentally relevant PTMs (including phosphorylation, lysine acetylation, sialylated N-glycosylation, and cysteine modifications). We demonstrate that protein abundance and dynamic PTMs show significant temporal changes during CBO development related to neuronal differentiation and energy metabolism, whereas calcium signaling is mainly regulated by dynamic PTMs. We further show that synaptic protein content correlated with neurotransmitter levels, and we detected astroglia beyond day 100. Lastly, comparative analysis showed proteomic similarities between CBOs and human fetal brain tissue, supporting the physiological relevance of CBOs. Overall, our study presents a temporal atlas of protein and PTM abundance in CBOs and provides a valuable resource for studying neurodevelopment in neural organoids.
Differential splice isoforms of mouse CDK2 play functionally redundant roles during mitotic and meiotic division
Authors: Palmer Nathan , Talib S. Zakiah A. , Ow Jin Rong , Tabaglio Tommaso , Goh Christine M.F. , Zhao Li Na , Guccione Ernesto , Liu Kui , Kaldis Philipp
Published: September 2024

In most mammals, the cell cycle kinase; cyclin-dependent kinase 2 (CDK2) is expressed as two major isoforms due to the inclusion or exclusion of an alternatively spliced exon. The shorter CDK2 isoform: CDK2S, is expressed constitutively during the cell cycle and can be detected in many different tissue types. In contrast, the longer isoform: CDK2L, shows preferential expression in meiotically dividing cells of the germ cells and upon S-phase entry during mitotic cell division. Both CDK2L and CDK2S form heteromeric complexes with cyclins A2 and E1in vitro. However, complexes comprised of each isoform differ considerably in their kinase activity towards known CDK substrates. It is currently unknown whether the long and short isoforms of CDK2 play functionally different rolesin vivoduring either mitotic and meiotic divisions as conventional knockout methodology leads to the loss of both isoforms. In this study, we find that both CDK2L and CDK2S are sufficient to support both mitotic and meiotic division when expressed in the absence of the other. This data contributes to the explanation of the apparent tolerance of the evolutionary loss of CDK2L expression in humans.
Using a Bacterial Protein to Selectively Target Bacterial Biofilms: Treatment of S. epidermidis Biofilms with Targeted Photothermal Gold Nanoparticles
Authors: Amarasekara Dhanush L. , Somarathne Radha P. , Shaikh Tanveer , Hejny Madison A. , McCaffrey Elizabeth R. , Fitzkee Nicholas C.
Published: September 2024

Biofilm-related infections are associated with high mortality and morbidity, combined with increased treatment costs. Traditional antibiotics are becoming less effective due to the emergence of drug-resistant bacterial strains. The need to treat biofilms on medical implants is particularly acute, and one persistent challenge is selectively directing nanoparticles to the biofilm site. Here, we present a protein-based functionalization strategy that targets the extracellular matrix of biofilms. The protein, derived from the extracellularStaphylococcus epidermidisautolysin, directs nanoparticles toS. epidermidiscell wall components, which are not expected to be present in mammalian tissues. This functionalization is applied to a gold nanoparticle (AuNP) core, along with elastin-like polypeptides (ELPs), which generate a robust photothermal response. In addition to biofilm targeting, the particles exhibit low protein binding, and the photothermal conversion can be modulated by changing the ELP transition temperature. These functionalized AuNPs strongly interact with biofilms under static and flow conditions but exhibit weak interactions with serum-coated surfaces. Near-infrared laser irradiation resulted in a 10,000-fold improvement in killing efficiency compared to untreated controls (p < 0.0001). The targeting strategy utilized here represents a versatile approach to targeting drug-resistant infections and could be readily expanded to other anti-biofilm nanoparticle platforms.

Graphical Abstract