bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacokinetics of propofol in severely obese surgical patients
Authors: Braathen Martin Rygh , Rigby‐Jones Ann E. , Ræder Johan , Spigset Olav , Heier Tom
Published: March 2024

Background

Existing PK models of propofol include sparse data from very obese patients. The aim of this study was to develop a PK model based on standardised surgical conditions and spanning from normal‐weight up to, and including, a high number of very obese patients.

Methods

Adult patients scheduled for laparoscopic cholecystectomy or bariatric surgery were studied. Anaesthesia was induced with propofol 2 mg/kg adjusted body weight over 2 min followed by 6 mg/kg/h adjusted body weight over 30 min. For the remainder of the operation anaesthesia was maintained with sevoflurane. Remifentanil was dosed according to clinical need. Eight arterial samples were drawn in a randomised block sampling regimen over a span of 24 h. Time‐concentration data were analysed by population PK modelling using non‐linear mixed‐effects modelling.

Results

Four hundred and seventy four serum propofol concentrations were collected from 69 patients aged 19–60 years with a BMI 21.6–67.3 kg/m2. Twenty one patients had a BMI above 50 kg/m2. A 3‐compartment PK model was produced wherein three different body weight descriptors and sex were included as covariates in the final model. Total body weight was found to be a covariate for clearance and Q3; lean body weight for V1, V2 and Q2; predicted normal weight for V3 and sex for V1. The fixed allometric exponent of 0.75 applied to all clearance parameters improved the performance of the model. Accuracy and precision were 1.4% and 21.7% respectively in post‐hoc performance evaluation.

Conclusion

We have developed a new PK model of propofol that is suitable for all adult weight classes. Specifically, it is based on data from an unprecedented number of individuals with very high BMI.
Dual treatment with kynurenine pathway inhibitors and NAD+ precursors synergistically extends life span in Drosophila
Authors: Gabrawy Mariann M. , Westbrook Reyhan , King Austin , Khosravian Nick , Ochaney Neeraj , DeCarvalho Tagide , Wang Qinchuan , Yu Yuqiong , Huang Qiao , Said Adam , Abadir Michael , Zhang Cissy , Khare Pratik , Fairman Jennifer E. , Le Anne , Milne Ginger L. , Vonhoff Fernando J. , Walston Jeremy D. , Abadir Peter M.
Published: March 2024

Tryptophan catabolism is highly conserved and generates important bioactive metabolites, including kynurenines, and in some animals, NAD+. Aging and inflammation are associated with increased levels of kynurenine pathway (KP) metabolites and depleted NAD+, factors which are implicated as contributors to frailty and morbidity. Contrastingly, KP suppression and NAD+ supplementation are associated with increased life span in some animals. Here, we used DGRP_229 Drosophila to elucidate the effects of KP elevation, KP suppression, and NAD+ supplementation on physical performance and survivorship. Flies were chronically fed kynurenines, KP inhibitors, NAD+ precursors, or a combination of KP inhibitors with NAD+ precursors. Flies with elevated kynurenines had reduced climbing speed, endurance, and life span. Treatment with a combination of KP inhibitors and NAD+ precursors preserved physical function and synergistically increased maximum life span. We conclude that KP flux can regulate health span and life span in Drosophila and that targeting KP and NAD+ metabolism can synergistically increase life span.
Variation in amphibian maturation rates influences population vulnerability to disease‐induced declines
Authors: Scheele B. C. , Webb R. J. , Hua X. , Hollanders M.
Published: March 2024

Understanding factors that influence population‐level responses to emerging threats in declining species is crucial for informed conservation action. In amphibian species impacted by the chytrid fungus (Batrachochytrium dendrobatidis), a pathogen that has caused amphibian declines globally, a commonly reported pattern is that more severe population declines tend to occur at higher elevations. Previous research has suggested that this pattern could be driven by reduced environmental suitability for chytrid fungus at lower elevations. However, delayed amphibian maturation, which is common in cold, high elevation populations, could also increase vulnerability to population decline. Here, we tackle this key knowledge gap, focusing on the critically endangered corroboree frogs (Pseudophryne corroboree and P. pengilleyi), which have experienced a pattern of extirpation at higher elevations, with remnant populations persisting at lower elevations. First, we quantify the age structure of two extant low elevation P. pengilleyi populations and museum specimens (both species) collected before the emergence of chytrid fungus in Australia. Male age to maturation varied from 1 to 3 years, with the extant population with higher chytrid prevalence displaying severe age structure truncation. Second, we use population simulations to calculate elasticity values under a range of scenarios with varying ages to maturation and chytrid‐associated mortality. When the population growth rate was fixed at 1, adult survival became increasingly important as age to maturation increases, particularly under a scenario of high chytrid‐associated mortality. Our simulation results indicate that delayed maturation could be a previously underappreciated factor associated with an increased risk of amphibian population decline and that earlier maturation could contribute to population persistence. Our study highlights the importance of examining variation in life history traits to better understand population‐level responses to novel threats and guide the development of appropriate conservation actions.
Filling the gap of phonation in reptiles: First record of oral emission of the worm lizard, Amphisbaena alba
Authors: Guilhon Bruno Ferreira , de Oliveira Cicero Ricardo , Quirino Tatiana Feitosa , Wachlevski Milena , Passos Daniel Cunha
Published: March 2024

So far, the phonation among worm lizards (Amphisbaenia) was virtually unknown, but herein we present for the first time a loud and clear record of sound emission by an amphisbaenian and its acoustic parameters. We observed an adult female of Amphisbaena alba emitting a high‐pitched sound, able to be heard a few meters away by a human ear. The sound was emitted with the mouth wide open and consisted of a short well‐defined note, presenting harmonics and frequency modulation. Based on the context of display and the body posture of the individual, we suggest that the oral emission of A. alba may be considered a defensive sound emission. However, based on the spectral structure of emission within hearing acuity reported for the species, we cannot disregard the possibility that this sound might act in communication with conspecifics. Beyond raising possible defensive and intra‐specific communication roles for the sound emissions of worm lizards, our findings contribute to the understanding of acoustic communication in tetrapods through the analysis of sounds produced by these fossorial reptiles.
Does it matter how we ship the good apples out? On specific tariffs, transport modes, and agricultural export prices
Authors: Fiankor Dela‐Dem Doe , Dalheimer Bernhard , Curzi Daniele , Hoffmeister Onno , Brümmer Bernhard
Published: March 2024

Free‐on‐board (FOB) export prices for identical products from the same origin often differ across destinations, even when accounting for the trade costs and attributes of the destination country. One explanation for this observed price difference is per‐unit trade costs, and the ability of exporters to vary their markups and/or product quality. Using a novel dataset that details trade flows between countries by mode of transport, we estimate the transport mode‐specific effect of a per‐unit trade cost, specifically specific tariffs, on the FOB export prices of agricultural products. We find an elasticity of specific tariffs to export prices of 1.8%. However, the estimates are heterogeneous across modes of transport. The elasticity of specific tariffs to export prices is 2% for air transport, 5% for road transport, and  .3% for sea cargo. Since the observed positive export price effect can reflect product quality differences or markups, we account for the quality element and find that for a given product quality, markups increase with increasing specific tariffs. This form of price discrimination is less pronounced for higher‐quality products that are predominantly shipped by air.
Pubertal testicular volume references for ruler, orchidometer, and ultrasonography measurements based on a longitudinal follow‐up
Authors: Koskela Mikael , Virtanen Helena E. , Rodprasert Wiwat , Jahnukainen Kirsi , Toppari Jorma , Koskenniemi Jaakko J.
Published: March 2024

Background

Testicular volume is a marker of male pubertal development. Various clinical conditions and their treatments may influence testicular growth.

Objectives

To create ruler‐based age‐dependent pubertal testicular volume references that enable calculation of standard deviation (SD) scores.

Materials and Methods

Study cohort comprised 65 boys who attended clinical examination twice a year from the age of 8.5 years until the attainment of final testicular size. Forty‐nine (75.4%) boys completed the follow‐up and 16 (24.6%) boys dropped out before the attainment of final post‐pubertal testicular size. At each follow‐up visit testicular size was measured with a ruler, orchidometer, and ultrasonography. LMS or LMSP method served as the technique for creating reference growth curves for testicular volumes. Using the novel references for ruler measurements, development of SD scores was assessed in a cohort of boys with unilateral cryptorchidism.

Results

Reference growth curves were constructed separately for ruler, orchidometer, and ultrasonography measurements. Median orchidometer volume of 4 mL, marker of male pubertal onset, occurred at the age of 11.7 years, whereas +2SD curve surpassed 4 mL at 10.2 years and −2SD curve at 13.7 years. Modeled ages at the attainment of 4 mL testicular volume based on ruler measurements were 9.7 years for +2SD curve, 11.5 years for median curve, and 13.6 years for −2SD curve. Ultrasonography‐based volume of 1.3 mL corresponded with the median modeled orchidometer‐based volume of 4 mL. In boys with unilateral cryptorchidism, ruler‐based SD scores decreased during puberty in undescended testes, but not in descended testes.

Discussion and Conclusion

The present study provides reference values for pubertal testicular volume measured with a ruler enabling an age‐dependent assessment of testicular size. Comparison with measurements by an orchidometer and ultrasonography is also presented.
Associations between arterial health and sexual function in women aged 60–64 years
Authors: Virkkunen Viivi , Kero Katja , Koivisto Mari , Niiranen Teemu , Heinonen Olli , Stenholm Sari , Polo‐Kantola Päivi
Published: March 2024

Introduction

Female sexual dysfunction is very common, but its determinants remain under‐investigated. Vasculogenic impairments are suggested to be related to female sexual dysfunction, but previous literature regarding the association is scarce. This study aims to study the association between arterial health and female sexual function in women in their 60s.

Material and methods

The sample for this cross‐sectional study comprised 117 women (aged 60–64 years) who participated in the Finnish Retirement and Aging study. Arterial health was measured according to the participants' pulse wave velocity, ankle–brachial index, blood pressure, and pulse pressure. Sexual function was measured using the Female Sexual Function Index, which resulted in a total score and six sub‐scores. Associations were examined using multivariable regression analyses, which were adjusted for age, relationship happiness, systemic menopausal hormone therapy and/or local estrogen, smoking, alcohol risk use, body mass index, and depressive symptoms.

Results

Higher diastolic blood pressure was associated with a higher total Female Sexual Function Index score (β = 0.24, 95% confidence interval [CI] 0.07–0.41) and with higher desire (β = 0.02, 95% CI 0.01–0.04), arousal (β = 0.04, 95% CI 0.01–0.08), lubrication (β = 0.04, 95% CI 0.002–0.08), satisfaction (β = 0.03, 95% CI 0.003–0.05), and pain (β = 0.06, 95% CI 0.02–0.10) sub‐scores. Also, higher ankle–brachial index was associated with higher satisfaction sub‐score (β = 2.10, 95% CI 0.44–3.73) and lower pulse pressure was associated with higher orgasm sub‐score (β = 0.03, 95% CI 0.0002–0.06). Other associations between ankle–brachial index and Female Sexual Function Index scores were statistically insignificant, but considering the magnitude the findings may imply clinical significance. Systolic blood pressure and pulse wave velocity were not associated with sexual function.

Conclusions

This study suggested a plausible association between higher diastolic blood pressure and female sexual function, but considering clinical significance our findings suggest an association between higher ankle–brachial index and good sexual function in women in their 60s.
Progestogens in women with threatened miscarriage or recurrent miscarriage: A meta‐analysis
Authors: Zhao Yunli , D'Souza Rohan , Gao Ya , Hao Qiukui , Kallas‐Silva Lucas , Steen Jeremy P. , Guyatt Gordon
Published: March 2024

Introduction

Clinical practice guidelines provide inconsistent recommendations regarding progestogen supplementation for threatened and recurrent miscarriage. We conducted a systematic review and meta‐analysis to assess the effectiveness and safety of progestogens for these patients.

Material and methods

We searched Medline, Embase, and Cochrane Central Registry of Controlled Trials up to October 6, 2023 for randomized control trials (RCTs) comparing progestogen supplementation to placebo or no treatment for pregnant women with threatened or recurrent miscarriage. We assessed the risk of bias using a modified version of the Cochrane risk‐of‐bias tool and the certainty of evidence using the GRADE approach.

Results

Of 15 RCTs (6616 pregnancies) reporting on threatened or recurrent miscarriage, 12 (5610 pregnancies) reported on threatened miscarriage with or without a prior history of miscarriage. Results indicated that progesterone probably increases live births (relative risk (RR) 1.04, 95% confidence interval (CI) 0.99–1.10, absolute increase 3.1%, moderate certainty). Of these RCTs, three (1973 pregnancies) reporting on threatened miscarriage with a prior history of miscarriage indicated that progesterone possibly increases live births (RR 1.06, 95% CI: 0.97–1.16, absolute increase 4.4%; low certainty), while four (2540 pregnancies) reporting on threatened miscarriage and no prior miscarriage left the effect very uncertain (RR 1.02, 95% CI: 0.96–1.10, absolute increase 1.7%; very low certainty). Three trials reporting on 1006 patients with a history of two or more prior miscarriages indicated progesterone probably increases live births (RR 1.08, 95% CI: 0.98–1.19, absolute increase 5.7%, moderate certainty). Six RCTs that reported on 2979 patients with at least one prior miscarriage indicated that progesterone probably increases live births (RR 1.07, 95% CI: 1.01–1.13, absolute increase 5.0%; moderate certainty). Progesterone probably has little or no effect on congenital anomalies (RR 1.06, 95% CI: 0.76–1.48, absolute increase 0.1%; moderate certainty), and other serious adverse pregnancy events (RR 1.07, 95% CI: 0.83–1.40, absolute increase 0.2%, moderate certainty).

Conclusions

In women at increased risk of pregnancy loss, progestogens probably increase live births without increasing adverse maternal and neonatal events. It remains possible that the benefit is restricted to those with prior miscarriages.
Prediction of preterm birth in women with fetal growth restriction – Is the weekly change in sFlt‐1/PlGF ratio or PlGF levels useful?
Authors: Hong Jesrine , Crawford Kylie , Cavanagh Erika , Clifton Vicki , Kumar Sailesh
Published: March 2024

Introduction

To assess the rate of change in soluble fms‐like tyrosine kinase‐1/placental growth factor (sFlt‐1/PlGF) ratio and PlGF levels per week compared to a single sFlt‐1/PlGF ratio or PlGF level to predict preterm birth for pregnancies complicated by fetal growth restriction.

Material and methods

A prospective cohort study of pregnancies complicated by isolated fetal growth restriction. Maternal serum PlGF levels and the sFlt‐1/PlGF ratio were measured at 4‐weekly intervals from recruitment to delivery. We investigated the utility of PlGF levels, sFlt‐1/PlGF ratio, change in PlGF levels per week or sFlt‐1/PlGF ratio per week. Cox‐proportional hazard models and Harrell's C concordance statistic were used to evaluate the effect of biomarkers on time to preterm birth.

Results

The total study cohort was 158 pregnancies comprising 91 (57.6%) with fetal growth restriction and 67 (42.4%) with appropriate for gestational age controls. In the fetal growth restriction cohort, sFlt‐1/PlGF ratio and PlGF levels significantly affected time to preterm birth (Harrell's C: 0.85–0.76). The rate of increase per week of the sFlt‐1/PlGF ratio (hazard ratio [HR] 3.91, 95% confidence interval [CI]: 1.39–10.99, p = 0.01, Harrell's C: 0.74) was positively associated with preterm birth but change in PlGF levels per week was not (HR 0.65, 95% CI: 0.25–1.67, p = 0.37, Harrell's C: 0.68).

Conclusions

Both a high sFlt‐1/PlGF ratio and low PlGF levels are predictive of preterm birth in women with fetal growth restriction. Although the rate of increase of the sFlt‐1/PlGF ratio predicts preterm birth, it is not superior to either a single elevated sFlt‐1/PlGF ratio or low PlGF level.
Machine perfusion preservation highlights from the Congress of the European Society of Organ Transplantation 2023
Authors: Faria Isabella , Vidgren Mathias , Canizares Stalin , Devos Lene , Reichel Katrin , Oniscu Gabriel C. , Martins Paulo N.
Published: March 2024

The 21st Congress of the European Society of Organ Transplantation (ESOT), held on September 17–20th, 2023, in Athens, Greece, was a pivotal event in transplantation, focusing on the theme “Disruptive Innovation, Trusted Care.” The congress attracted a global audience of 2 826 participants from 82 countries, emphasizing its international significance. Machine perfusion, as a groundbreaking technology in organ transplantation, was one of the central focuses of the conference. This year's meeting had a remarkable increase in accepted abstracts on machine perfusion, evidencing its growing prominence in the field. The collective findings from these abstracts highlighted the efficacy of machine perfusion in improving organ viability and transplant outcomes. Studies demonstrated improvements in graft survival and reduction in complications, as well as novel uses and techniques. Furthermore, the integration of machine perfusion with regenerative medicine and its application across multiple organ types were significant discussion points. The congress also highlighted the challenges and solutions in implementing machine perfusion in clinical settings, emphasizing the importance of practical training and international collaboration for advancing this technology. ESOT 2023 served as a crucial platform for disseminating scientific advancements, fostering practical learning, and facilitating international collaborations in organ transplantation. The congress underscored the evolution and importance of machine perfusion technology, marking a significant step forward in enhancing patient outcomes in the field of organ transplantation.
Myalgic encephalomyelitis/chronic fatigue syndrome from current evidence to new diagnostic perspectives through skeletal muscle and metabolic disturbances
Authors: Pietrangelo Tiziana , Cagnin Stefano , Bondi Danilo , Santangelo Carmen , Marramiero Lorenzo , Purcaro Cristina , Bonadio Raphael Severino , Di Filippo Ester Sara , Mancinelli Rosa , Fulle Stefania , Verratti Vittore , Cheng Xuanhong
Published: March 2024

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a demanding medical condition for patients and society. It has raised much more public awareness after the COVID‐19 pandemic since ME/CFS and long‐COVID patients share many clinical symptoms such as debilitating chronic fatigue. However, unlike long COVID, the etiopathology of ME/CFS remains a mystery despite several decades' research. This review moves from pathophysiology of ME/CFS through the compelling evidence and most interesting hypotheses. It focuses on the pathophysiology of skeletal muscle by proposing the hypothesis that skeletal muscle tissue offers novel opportunities for diagnosis and treatment of this syndrome and that new evidence can help resolve the long‐standing debate on terminology.
Dose safety and pharmacodynamics of subcutaneous bupivacaine in a novel extended‐release microparticle formulation: A phase 1, dose‐ascending study in male volunteers
Authors: Jensen Elisabeth Kjær , Bøgevig Søren , Balchen Torben , Springborg Anders Holten , Royal Mike Allan , Storgaard Ida Klitzing , Lund Trine Meldgaard , Møller Kirsten , Werner Mads Utke
Published: March 2024

A novel microparticle‐based extended‐release local anaesthetic containing a bupivacaine/poly‐lactic‐co‐glycolic acid (PLGA; LIQ865A) or plain bupivacaine (LIQ865B) was examined in a first‐in‐human trial. The objectives were to examine the dose safety/tolerability and pharmacodynamics. Randomized subcutaneous injections of LIQ865A (n = 16) or LIQ865B (n = 12) and diluent, contralaterally, were administered in a dose‐ascending manner (150‐ to 600‐mg bupivacaine). Subjects were admitted 24 h post‐injection and followed for 30 days post‐injection. The risk ratios (RRs; 95% CI) of erythematous reactions for LIQ865A versus diluent was 9.00 (1.81–52.23; P = 0.006) and for LIQ865B versus diluent 2.50 (0.69–9.94; P = 0.37). The RR for the development of hematomas (LIQ865A versus diluent) were 3.25 (1.52–8.16; P = 0.004) and 4.00 (0.72–24.89; P = 0.32) (LIQ865B versus diluent). Subcutaneous indurations persisting for 4–13 weeks were seen in 6/16 subjects receiving LIQ865A. One subject receiving LIQ865A (600‐mg bupivacaine) developed intermittent central nervous system (CNS) symptoms of local anaesthetic systemic toxicity (85 min to 51 h post‐injection) coinciding with plasma peak bupivacaine concentrations (490–533 ng/ml). Both LIQ865 formulations demonstrated dose‐dependent hypoesthesia and hypoalgesia. The duration of analgesia ranged between 37 and 86 h. The overall number of local adverse events, however, prohibits clinical application without further pharmacological modifications.
Arrestin‐centred interactions at the membrane and their conformational determinants
Authors: Underwood Owen , Haider Raphael Silvanus , Sanchez Julie , Canals Meritxell
Published: March 2024

More than 30 years after their discovery, arrestins are recognised multiprotein scaffolds that play essential roles in G protein‐coupled receptor (GPCR) regulation and signalling. Originally named for their capacity to hinder GPCR coupling to G proteins and facilitate receptor desensitisation, arrestins have emerged as key hubs for a myriad of other functions, including receptor internalisation and scaffolding of signalling complexes. Recent structural studies have started to provide snapshots of the complexes formed by GPCRs and arrestins, supporting a wealth of biochemical data delineating the molecular determinants of such interactions. Furthermore, biophysical techniques have also provided key information with regards to the basal and active conformations of arrestins, and how these are affected upon GPCR activation. Here, we review the most recent advances on our understanding of GPCR‐arrestin complexes, from structure to interactions of arrestins with the lipid bilayer and other proteins. We also present an updated view on the development of tools to study the conformational flexibility of arrestins, with the potential to provide experimental data to describe the dynamic models of arrestin activation.
Melatonin and its bioisosteres as potential therapeutic agents for the treatment of retinopathy of prematurity
Authors: Osipova N. A. , Panova A. Y. , Efremov A. M. , Lozinskaya N. A. , Beznos O. V. , Katargina L. A.
Published: March 2024

We conducted a study on the impact of intraperitoneal injections of melatonin and its three bioisosteres (compounds1–3) on the development of oxygen‐induced retinopathy in newborn rats during a 21‐day experiment. It was demonstrated that melatonin and its analogues1–3effectively reduce the total protein concentration in the vitreous body of rat pups, decrease concentration of VEGF‐A, and lower the level of oxidative stress (as indicated by normalization of antioxidant activity in the vitreous body). Melatonin and its analogues1–3equally normalize the level of VEGF‐A. Analogues1and2even exceed melatonin in their ability to reduce protein influx into the vitreous body. However, analogue2had no effect on antioxidant activity, while analogues1and3caused a significant increase in this parameter, with analogue3even slightly exceeding melatonin. Thus, it can be concluded that analogues1–3are comparable to melatonin and can be utilized as potential therapeutic agents for the treatment of retinopathy of prematurity.
Probing the Representational Structure of Regular Polysemy via Sense Analogy Questions: Insights from Contextual Word Vectors
Authors: Li Jiangtian , Armstrong Blair C.
Published: March 2024

Regular polysemes are sets of ambiguous words that all share the same relationship between their meanings, such as CHICKEN and LOBSTER both referring to an animal or its meat. To probe how a distributional semantic model, here exemplified by bidirectional encoder representations from transformers (BERT), represents regular polysemy, we analyzed whether its embeddings support answering sense analogy questions similar to “is the mapping between CHICKEN (as an animal) and CHICKEN (as a meat) similar to that which maps between LOBSTER (as an animal) to LOBSTER (as a meat)?” We did so using the LRcos model, which combines a logistic regression classifier of different categories (e.g., animal vs. meat) with a measure of cosine similarity. We found that (a) the model was sensitive to the shared structure within a given regular relationship; (b) the shared structure varies across different regular relationships (e.g., animal/meat vs. location/organization), potentially reflective of a “regularity continuum;” (c) some high‐order latent structure is shared across different regular relationships, suggestive of a similar latent structure across different types of relationships; and (d) there is a lack of evidence for the aforementioned effects being explained by meaning overlap. Lastly, we found that both components of the LRcos model made important contributions to accurate responding and that a variation of this method could yield an accuracy boost of 10% in answering sense analogy questions. These findings enrich previous theoretical work on regular polysemy with a computationally explicit theory and methods, and provide evidence for an important organizational principle for the mental lexicon and the broader conceptual knowledge system.
Determinants of hyperparathyroidism in children after kidney transplantation
Authors: Glaberson Wendy , Seeherunvong Wacharee , Gaynor Jeffrey J. , Katsoufis Chryso , Defreitas Marissa , Bao Yong , Freundlich Michael , Ciancio Gaetano , Abitbol Carolyn , Chandar Jayanthi
Published: March 2024

Introduction

Hyperparathyroidism (HPT) can contribute to metabolic bone disease following kidney transplantation. We evaluated post‐transplant trends in intact parathyroid hormone (iPTH) and determined predictors of HPT in pediatric kidney transplant (KTx) recipients.

Methods

In this single‐center study, retrospective data were collected on 88 children from 2013 to 2019. Data collected included dialysis vintage, biochemical parameters, post‐transplant trends in iPTH, 25(OH)Vitamin D levels and estimated glomerular filtration rate (eGFR ml/min/1.73 m2). Pre‐transplant treatment for HPT was quantified with a Treatment Burden score (TB, score range: 0‐100). After log‐transforming skewed variables (iPTH and eGFR), multivariable linear regression was performed to determine predictors of log {iPTH} at 6 and 36 months (mo) post‐transplant.

Results

Median age was 12.8 (range: 1.9‐20.5) years, and dialysis vintage was 11.2 (range: 0.0‐112.9) months. The majority were of Hispanic and African Ancestry (77.3%). Median post‐transplant iPTH was 69.5 (range: 1.8‐306.8) pg/ml at 6 mo with a gradual downward trend to 59.0 (range: 28.0‐445.0) pg/ml at 36 mo. Significant multivariable predictors of higher log {iPTH} post‐transplant included longer dialysis vintage, higher TB, and lower log{eGFR} at 6 mo, and higher TB, lower log{eGFR}, and deceased donor transplant at 36 mo.

Conclusions

Recognition of risk factors for HPT and monitoring iPTH post‐transplant may facilitate timely interventions to mitigate cardiovascular and bone disease in pediatric KTx recipients.

Key Message

Describe serial trends in intact PTH after kidney transplantation.

Pre‐ and post‐transplant factors that contribute to persistence or re‐occurrence of hyperparathyroidism after kidney transplantation in children include longer dialysis vintage, high pre‐transplant treatment burden and decreased post‐transplant GFR.

Recognition of these factors, and monitoring intact PTH after kidney transplantation, could facilitate timely interventions to mitigate cardiovascular and bone disease in children.
Developments and management of the Wakehurst North American prairie
Authors: Harrison Jack
Published: March 2024

The management of the new North American prairie at Wakehurst Place is described, including the difficulties faced when some species threaten to become dominant.
Effects of home‐based exergaming on cardio‐metabolic and cognitive health in physically inactive individuals
Authors: Melmer Andreas , Martin‐Niedecken Anna Lisa , Wehrli Wanda , Lüchinger Patrick , Riederer Yanick , Scott Sam , Pickles Jordan , Niedecken Stephan , Flagmeier David , Villiger Stephan , Jurt Roman , Kind Nicole , Witthauer Lilian , Schättin Alexandra , Stettler Christoph
Published: March 2024

Aims

To examine the effects of a home‐based exergame training over 6 weeks on cardio‐metabolic and cognitive health, as well as training adherence, in physically inactive individuals.

Materials and Methods

Twenty participants were equipped with an exergame system specifically designed for use at home. Each participant performed at least three weekly exercise sessions at ≥80% of their individual maximum heart rate, over 6 weeks. Exercise duration increased biweekly until 75 min of vigorous exercise were performed in Weeks 5 and 6. Maximum oxygen uptake (VO2max), cardio‐metabolic profiling, and neuro‐cognitive tests were performed at baseline and study end. Additionally, training adherence was assessed via training diaries.

Results

After 6 weeks of home‐based exergaming, VO2max increased significantly, while there was a significant decrease in heart rate (resting and maximum), blood pressure (systolic, diastolic and mean), and low‐density lipoprotein cholesterol. Dynamic balance and reaction time improved after 6 weeks of exergaming. Training adherence was 88.4%.

Conclusions

Home‐based exergaming induced a clinically relevant increase in VO2max, a determinant of cardiovascular health, accompanied by further improvements in cardiovascular, metabolic and neuro‐cognitive parameters. Exergaming may, therefore, offer an innovative approach to increasing regular physical activity, improving metabolic risk profile, and preventing chronic diseases.
Recognising the rights of nature: How have the courts fared?
Authors: Ogboru Tolulope N.
Published: March 2024

The Rights of Nature (RoN) concept is an evolving theory in environmental law. It advocates that natural objects be respected and allowed to exist, thrive and flourish for themselves and not for utilitarian purposes. However, attempts to apply the rights often result in litigation. The outcomes of these cases have grave implications for the impact of the RoN concept on the development of jurisprudence and environmental protection, which will further determine its acceptance or rejection by the international community. An examination of some key cases reveals some positive developments that can enhance the implementation of the concept, but it also demonstrates that there are some challenges in the approach adopted by the courts. The article concludes that the RoN can be a jurisprudential tool to enhance environmental protection only where, in addition to well‐written constitutional and legislative provisions, court decisions in these cases are of practical consequences.
Synergistic effects of epoxyazadiradione (EAD) and paclitaxel against triple‐negative breast cancer cells
Authors: Sijisha Kunnathully Sudhan , Anusha Rajitha , Priya Sulochana
Published: March 2024

Background

Triple‐negative breast cancer (TNBC) is the most aggressive and chemo‐resistant form of breast cancer subtype, and chemotherapy is a vital treatment option for that. Paclitaxel is an effective chemo drug for TNBC. However, in clinical settings, paclitaxel has adverse side effects. The synergistic combination is the most promising method for overcoming undesirable toxicity and achieving a beneficial therapeutic outcome. Previous reports, including our study, showed certain anticancer potential of epoxyazadiradione (EAD), the neem limonoid, in different types of cancer cells, including TNBC.

Objective

This study was designed to investigate the possible synergistic effects of EAD and paclitaxel against TNBC cells.

Methods

We examined the effects of EAD and paclitaxel alone and in combination in MDA‐MB 231 cells, and the percentage cytotoxicity was used to calculate synergism. Characteristic apoptotic changes were observed by visualizing cellular morphology, nuclear fragmentation and membrane integrity. We further estimated anti‐migratory potential of experimental compounds by wound healing assay. The reduction in inflammation during combinatorial treatment was evaluated by observing NF‐κB translocation.

Results

The combined treatment with EAD (5 μM) and paclitaxel (5 nM), which were used at doses lower than their individual IC50 concentrations, showed a synergistic effect in MDA‐MB‐231 cells. This combination effectively induced apoptosis and antimigration and reduced the inflammatory reactions induced by the higher dose of paclitaxel.

Conclusion

To conclude, EAD could be the drug of choice for combined treatment with paclitaxel in a chemotherapy regimen.
Delaware County, Ohio, domestic relations court programs designed to reduce family conflict and reach agreements
Authors: Fuller Randall D. , Armstrong Amy
Published: March 2024

Families experiencing separation and divorce often find it difficult to provide emotional stability for children as the parents struggle with financial, parenting, and relationship decisions. The effect on children can be especially precarious. Adverse childhood experiences, or ACEs, are risk factors that potentially affect children for the rest of their lives. Parental separation and divorce are identified as adverse childhood experiences and the experiences of stress and loss, reduced parental effectiveness, and exposure to parental conflict, among other stressors, may explain some of the negative outcomes often observed in children following divorce. It is essential that public institutions, including courts, are informed about the risks and protective factors associated with ACEs and resolve to mitigate the effects for children and families whom they serve. Domestic Relations Courts are uniquely equipped to address the effects that parental separation and divorce have on children, given the courts' authority to govern the legal divorce and custody process. The Domestic Relations Court in Delaware, Ohio, is committed to assisting families navigate separation and divorce in a way that is in the best interests of all, especially the children. The Court has created four specific programs to help litigants navigate their emotions, create new narratives, and explore solutions to conflict outside of trial. These innovative programs go beyond traditional court practices to treat the spouses and parents as unique individuals, giving them ample opportunities to address traumatic events and be validated for their lived experience. The suite of services includes Settlement Weeks, Neutral Evaluation, Co‐parent Coaching, and Brief Family Assessments. In the subsequent sections, we will delve into each program, exploring their promise for improving outcomes for the public, the litigants, and the court as a whole.
Decoding autumn phenology: Unraveling the link between observation methods and detected environmental cues
Authors: Kloos Simon , Klosterhalfen Anne , Knohl Alexander , Menzel Annette
Published: March 2024

Leaf coloring and fall mark the end of the growing season (EOS), playing essential roles in nutrient cycling, resource allocation, ecological interactions, and as climate change indicators. However, understanding future changes in autumn phenology is challenging due to the multitude of likely environmental cues and substantial variations in timing caused by different derivation methods. Yet, it remains unclear whether these two factors are independent or if methodological uncertainties influence the environmental cues determined. We derived start of growing season (SOS) and EOS at a mixed beech forest in Central Germany for the period 2000–2020 based on four different derivation methods using a unique long‐term data set of in‐situ data, canopy imagery, eddy covariance measurements, and satellite remote sensing data and determined their influence on a predictor analysis of leaf senescence. Both SOS and EOS exhibited substantial ranges in mean onset dates (39.5 and 28.6 days, respectively) across the different methods, although inter‐annual variations and advancing SOS trends were similar across methods. Depending on the data, EOS trends were advanced or delayed, but inter‐annual patterns correlated well (mean r = .46). Overall, warm, dry, and less photosynthetically productive growing seasons were more likely to be associated with a delayed EOS, while colder, wetter, and more photosynthetically productive vegetation periods resulted in an earlier EOS. In addition, contrary to recent results, no clear influence of pre‐solstice vegetation activity on the timing of senescence was detected. However, most notable were the large differences in sign and strength of potential drivers both in the univariate and multivariate analyses when comparing derivation methodologies. The results suggest that an ensemble analysis of all available phenological data sources and derivation methods is needed for general statements on autumn phenology and its influencing variables and correct implementation of the senescence process in ecosystem models.
History of the Hanse: Construction and deconstruction
Authors: Sicking Louis
Published: March 2024

This article explores 150 years of historiography of the Hanse, the premodern trade network of mainly Low German merchants and their towns. It focusses on the construction of its infrastructure (the Hanseatic History Association, its source publications and its journal) and on the deconstruction of viewing the history of the Hanse in terms of its rise, greatness and fall. Instead, it looks at three different ways to grasp and understand the Hanse: (1) The dynamics of the so‐called “formative” period, (2) The formalization of the Hanse, and (3) Recent critical re‐evaluations of the main source editions of the Hanse, and the use of discourse or political communication at the so‐called Hanse diets, the meetings of Hanse towns. Finally, the relevance of the Hanse for wider historical debates and its use for present‐day purposes is discussed.
You can go your own way: Conducting a signage audit in a health library
Authors: Wise Katie
Published: March 2024

Background

The Library and Knowledge Services at the Royal Berkshire NHS Foundation Trust has been at its current location since 1975 and, in September 2020, it was deemed necessary to examine the library environment and assess the signage.

Objectives

The main objective was to conduct a methodical assessment of all the current library signage in order to improve the library environment, wayfinding, and clarity.

Methods

A methodical signage audit was conducted by library staff, photographing signs, assigning them to categories, and creating a signage map.

Results

In total, 58 different signs were counted in the library. Of these, 22 signs were deemed satisfactory, 4 should be moved to a more appropriate location, 15 should be updated with a branded design and better messaging, and 17 were recommended for removal.

Discussion

The results demonstrated that there were three main areas where signage could be improved: reducing the quantity of signs, updating the language and design, and the use of ad hoc signage.

Conclusion

By assessing the signs and assigning categories and types, areas were identified as problem points that were impacting the library user's experience and small changes were implemented to improve the library environment.
When hidden politics become visible: Administrative burden experiences of older adults and professionals in home care
Authors: Benoit Maude , Marier Patrik
Published: March 2024

In the context of constraining services and support within public home care, this contribution analyses how older adults and home care workers experience and navigate administrative burdens. Relying on focus groups, interviews, and a survey conducted in the province of Québec (Canada), we demonstrate that older adults face an increasing number of administrative burdens designed to alter, delay, and restrict access to public services while homecare workers experience a loss of discretion in their practice due to the introduction of administrative requirements with dubious purposes. As such, administrative burdens play a vital role in the hidden politics of the welfare state and contribute to foster cynicism and a loss of faith in essential public services.
RETRACTED: Effects of loose combined cutting seton surgery on wound healing and pain in patients with high anal fistula: A meta‐analysis
Authors: Xi Jie , Li Wei , Li Tao , Cao Shuai , Wei Sheng‐Chao , Xu Jia‐Cheng , Bi Yu‐He
Published: March 2024

A meta‐analysis was conducted to evaluate the effects of loose combined cutting seton surgery on wound healing and pain in patients with high anal fistula, aiming to provide evidence‐based medical evidence for surgical method selection for these patients. A comprehensive computerized search of PubMed, Cochrane Library, EMBASE, Wanfang and China National Knowledge Infrastructure databases was conducted to collect all relevant studies published up to November 2023, evaluating the effects of loose combined cutting seton surgery in treating patients with high anal fistulas. Two researchers independently screened, extracted data, and assessed the quality of the identified studies. RevMan 5.4 software was employed for data analysis. Overall, 16 articles were included, comprising 1124 patients, with 567 undergoing loose combined cutting seton surgery and 557 undergoing simple cutting seton surgery. The analysis revealed patients undergoing loose combined cutting seton surgery had a higher rate of postoperative wound healing (97.44% vs. 81.69%, odds ratio [OR]: 7.49, 95% confidence interval [CI]: 4.29–13.10, p < 0.00001), shorter wound healing time (standardized mean differences [SMD]: −1.48, 95% CI: −1.89 to −1.08, p < 0.00001), lower postoperative wound pain scores (SMD: −2.51, 95% CI: −3.51 to −1.51, p < 0.00001), and a lower rate of postoperative complications (3.43% vs. 20.83%, OR: 0.13, 95% CI: 0.05–0.31, p < 0.00001). The current evidence suggests that compared to simple cutting seton surgery, loose combined cutting seton surgery in treating high anal fistulas can promote postoperative wound healing, shorten wound healing time, alleviate pain, and reduce the incidence of postoperative complications, making it a worthy clinical practice for widespread application.
Effect of percutaneous vertebroplasty versus percutaneous kyphoplasty on post‐operative wound pain in patients with osteoporotic vertebral compression fractures
Authors: Si Xiaojing , Shan Dongli , Huo li , Hu Yongjun , Zou Chuanqi , Wang Boxin , Cao Junxiong , Wu Wenjie
Published: March 2024

This research is intended to evaluate the efficacy of percutaneous vertebroplasty (PVP) versus percutaneous kyphoplasty (PKP) in osteoporotic vertebral compression fracture (OVCF), which is associated with post‐operative pain. Eligible studies were screened by searching multiple databases and sources such as PubMed, Cochrane and EMBASE for search terms updated to October 2023, and relevant literature sources were searched. Randomized, controlled, prospective or retrospective, and cohort studies were eligible. For the analysis of the primary results, an analysis of the data was carried out, such as mean difference (MD) or odds ratio (OR), and 95% confidence interval (CI). In the present research, 1933 research was screened in 4 databases, and 30 articles were chosen to be examined under strict exclusion criteria. No statistical significance was found in the use of bone cement in the PVP group and PKP (MD, −0.60; 95% CI, −1.40, 0.21, p = 0.15); PKP was associated with a reduced risk of cement leak compared with PVP group (OR, 2.18; 95% CI, 1.38, 3.46, p = 0.0009); no statistical significance was found in the wound VAS score in PVP operation compared with that of PKP (MD, 0.16; 95% CI, −0.07, 0.40, p = 0.17); no statistical significance was found between the time of PVP operation and the time of PKP operation (MD, −2.65; 95% CI, −8.91, 3.60, p = 0.41). Compared with PVP technology, the PKP treatment of osteoporotic vertebral compression fractures reduces post‐operative cement leakage, but there is no significant difference in the number of operative cement and wound VAS after operation. Nor did there appear to be a statistically significant difference in time between the two operations.
The infected diabetic foot: Modulation of traditional biomarkers for osteomyelitis diagnosis in the setting of diabetic foot infection and renal impairment
Authors: Coye Tyler L. , Crisologo P. Andrew , Suludere Mehmet A. , Malone Matthew , Oz Orhan K. , Lavery Lawrence A.
Published: March 2024

The objective of this paper was to investigate erythrocyte sedimentation rate (ESR) and c‐reactive protein (CRP) in diagnosing pedal osteomyelitis (OM) in patients with and without diabetes, and with and without severe renal impairment (SRI). This was a retrospective cohort study of patients with moderate and severe foot infections. We evaluated three groups: Subjects without diabetes (NDM), subjects with diabetes and without severe renal insufficiency (DM‐NSRI), and patients with diabetes and SRI (DM‐SRI). SRI was defined as eGFR <30. We evaluated area under the curve (AUC), cutoff point, sensitivity and specificity to characterize the accuracy of ESR and CRP to diagnose OM. A total of 408 patients were included in the analysis. ROC analysis in the NDM group revealed the AUC for ESR was 0.62, with a cutoff value of 46 mm/h (sensitivity, 49.0%; specificity, 76.0%). DM‐NSRI subjects showed the AUC for ESR was 0.70 with the cutoff value of 61 mm/h (sensitivity, 68.9%; specificity 61.8%). In DM‐SRI, the AUC for ESR was 0.67, with a cutoff value of 119 mm/h (sensitivity, 46.4%; specificity, 82.40%). In the NDM group, the AUC for CRP was 0.55, with a cutoff value of 6.4 mg/dL (sensitivity, 31.3%; specificity, 84.0%). For DM‐NSRI, the AUC for CRP was 0.70, with a cutoff value of 8 mg/dL (sensitivity, 49.2%; specificity, 80.6%). In DM‐SRI, the AUC for CRP was 0.62, with a cutoff value of 7 mg/dL (sensitivity, 57.1%; specificity, 67.7%). While CRP demonstrated relatively consistent utility, ESR's diagnostic cutoff points diverged significantly. These results highlight the necessity of considering patient‐specific factors when interpreting ESR results in the context of OM diagnosis.