bluuebunny/crossref_metadata_2025 huggingface dataset:
Exploring Anesthesiology Management of Living Donor Liver Transplantation: Survey From the Society for the Advancement of Transplant Anesthesia and the Korean Society for Transplantation Anesthesiologists
Authors: Crouch Cara E. , Ko Justin Sangwook , Hendrickse Adrian , Kumar Sathish S. , Little Michael , Chae Min Suk , Park Sun Young , Sakai Tetsuro
Published: September 2024

Introduction

While living donor liver transplantation (LDLT) serves as the predominant method of adult liver transplant (LT) in the Republic of Korea (ROK), it represents a minority of LT in the United States (US). A survey was conducted to gain insight into these nations’ anesthetic management.

Methods

An electronic questionnaire was distributed to directors of LT anesthesiology overseeing LDLT programs in both countries between May 2021 and October 2021.

Results

The response rate was 93.0% (100% [37/37] in the US and 80% [16/20] in the ROK). Both countries mainly adhered to deceased donor LT recipient management practices, including the frequency of routine pulmonary artery catheter use, transesophageal echocardiography, and point‐of‐care coagulation monitoring. Differences were observed in early extubation of recipients (US vs. ROK: 39.7% vs. 14.7% of all cases), participation in donor selection meetings (88.9% [32/36] vs. 6.3% [1/16], p < 0.0001), application of the Enhanced Recovery After Surgery donor protocol (69.4% [25/36] vs. 12.5% [2/16], p < 0.0001), and cell saver usage for donors (94.4% [34/36] vs. 18.8% [3/16], p < 0.0001). More ROK programs implemented simultaneous donor/recipient anesthesia supervision by a single anesthesiologist.

Conclusions

Several important differences were identified between the US and the ROK in adult LDLT anesthetic management.
Mass balance and pharmacokinetic characterization of zavegepant in healthy male subjects
Authors: Bhardwaj Rajinder , Donohue Mary , Madonia Jennifer , Anderson Matt S. , Matschke Kyle , Bertz Richard , Croop Robert , Liu Jing
Published: September 2024

Zavegepant, a high‐affinity, selective, small‐molecule calcitonin gene‐related peptide receptor antagonist, is approved as a nasal spray for acute treatment of migraine in adults. This phase I, open‐label, single‐center, single‐period, nonrandomized study in six healthy male subjects assessed mass balance recovery after a single 15‐min intravenous (IV) infusion dose of carbon‐14 ([14C])‐zavegepant. Blood, urine, and fecal samples were collected over 192 h for analysis of zavegepant in plasma and urine; total radioactivity (TR) in plasma, whole blood, urine, and feces; and zavegepant metabolite profiling and structural identification in plasma, urine, and feces. An average of 96.6% of radioactivity administered was recovered in excreta. Most TR (mean 84.9%) was recovered in the feces, indicating that biliary/fecal elimination was the main route. Volume of distribution of zavegepant based on the terminal phase (129 L) was higher than total body water (42 L), indicating substantial distribution into tissue. Total plasma clearance of zavegepant (220 mL/min) is identical to whole blood clearance given the blood/plasma partition ratio of 1, lower than typical hepatic blood flow (1450 mL/min). The observed plasma terminal half‐life of zavegepant was 6.8 h. Exposure to zavegepant accounted for ~90% of circulating plasma TR, suggesting that very low levels of uncharacterized circulating metabolites were present. Metabolite profiling did not identify any metabolites representing ≥10% of radioactivity in plasma, urine, or feces. A single IV infusion of 5 mg [14C]‐zavegepant was well tolerated in healthy male subjects. Disposition findings of IV [14C]‐zavegepant are applicable to the disposition of the approved zavegepant nasal spray.
Divergent Importance and Geographic Patterns in Threats to Birds and Mammals in China
Authors: Gao Xin , Liu Zhuoen , Corlett Richard T. , Jiang Zhigang , Hughes Alice , Ma Keping , Svenning Jens‐Christian , Feng Gang
Published: September 2024

Aim

Wildlife populations are continuing to decrease worldwide. Understanding the ranking and distribution of drivers of species declines is crucial to enable targeted actions to counteract major threats. However, few studies have assessed the relative importance and geographic distribution of threats to biodiversity in China, even for high‐profile groups such as birds and mammals. Therefore, this study aims to rank and map the distribution of threat to birds and mammals in China, which could provide novel insight into biodiversity conservation in China.

Location

China.

Methods

A database of different threats for 147 threatened bird species and 176 threatened terrestrial mammal species was obtained from China's Red List of Biodiversity published in 2021. We collated information on the distribution and threat categories for birds and mammals in China, aiming to classify, rank and map threats. We used Bray–Curtis dissimilarity index to examine the correlations of threats occurring simultaneously, and compared the distribution of habitat of threatened birds and mammals. In addition, we conducted threat ranking analyses of threatened birds and mammals between different orders and traits (body mass and clutch/litter sizes).

Results

The results showed that the most common threats to birds were habitat loss, hunting, human disturbance, agriculture, pollution and logging, while the most common threats to mammals were hunting, agriculture, logging, habitat loss, human disturbance and livestock farming or ranching. These threats showed different geographic patterns, and some threats frequently co‐occur as threat syndromes. Forests were the primary habitat for most threatened species, and orders formed by larger species with small clutch or litter sizes were more likely to be threatened.

Main Conclusions

We highlight the most common threats and key areas for conservation. Furthermore, focusing on clusters of co‐occurring threats may be the most effective way to aid recovery of threatened species, and targeted actions are needed to counter ongoing population declines in many groups. These actions should not be limited to the protection of regions where species are at risk of multiple significant threats, but should also include the maintenance and restoration of native forests and strategic planning of afforestation through planted forests.
Cost‐effectiveness of sodium‐glucose cotransporter‐2 inhibitors in the treatment of diabetic nephropathy in Japan
Authors: Maruyama‐Sakurai Keiko , Tachimori Hisateru , Saito Eiko , Kohsaka Shun , Segawa Yasumasa , Miyata Hiroaki , Igarashi Ataru
Published: September 2024

Aim

To assess the cost‐effectiveness of diabetic nephropathy treatment with sodium‐glucose cotransporter‐2 (SGLT2) inhibitors in Japanese clinical practice, considering diabetes‐related complications.

Materials and Methods

A population‐based Monte Carlo simulation was used to estimate the cost‐effectiveness for people with diabetic nephropathy who initiated pharmacotherapy with an SGLT2 inhibitor plus conventional treatment or conventional treatment alone, based on quality‐adjusted life‐years (QALYs) and healthcare costs. The Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation study (CREDENCE) and the Japanese Society for Dialysis Research statistical survey were the primary sources of probability and mortality, while Japanese Health Insurance Claims Data were the cost source. The state transition model included diabetic nephropathy, hospitalization due to cardiovascular disease, dialysis, and death. One‐way and probabilistic sensitivity analyses were used to explore model uncertainty.

Results

Using the threshold of JPY 5 000 000 per QALY, SGLT2 inhibitor plus conventional treatment was more cost‐effective than conventional treatment alone, with an incremental cost‐effectiveness ratio of JPY 654 309 per QALY. Treating 100 000 people, SGLT2 inhibitor plus conventional treatment prevented 2234 deaths and reduced 5793 fewer heart failure cases, 3967 fewer myocardial infarctions and stroke events. Sensitivity analysis affirmed the robustness of these results for patients aged under 70 years.

Conclusions

The SGLT2 inhibitor treatment appeared to be cost‐effective for the overall population of our study and particularly for younger patients (<70 years old). For older patients (≥70 years old), the cost‐effectiveness was less clear and may require further evaluation. Decision‐makers should consider this age‐based heterogeneity when making recommendations about SGLT2 inhibitor treatment.
Remission and relapse of diabetes after sleeve gastrectomy and one‐anastomosis gastric bypass: The Tehran Obesity Treatment Study
Authors: Sadeghi Sara , Hosseinpanah Farhad , Khalaj Alireza , Ebadinejad Amir , Mahdavi Maryam , Valizadeh Majid , Barzin Maryam
Published: September 2024

Aims

To evaluate the rates and predictors of remission and relapse of type 2 diabetes mellitus (T2DM) in individuals with T2DM undergoing sleeve gastrectomy (SG) or one‐anastomosis gastric bypass (OAGB).

Methods

An observational prospective study with 5 years of follow‐up was conducted in a total of 891 patients (82.5% female) with concomitant T2DM and obesity (body mass index ≥ 30.0 kg/m2) undergoing SG or OAGB between March 2013 and March 2021. T2DM remission was defined as achieving a glycated haemoglobin (HbA1c) level < 48 mmol/mol and a fasting plasma glucose (FPG) level <7 mmol/L, and being off glucose‐lowering agents/insulin. T2DM relapse was defined as when FPG or HbA1c reverted to the diabetic range (≥7 mmol/L and ≥48 mmol/mol, respectively), or there was a need for pharmacotherapy.

Results

After bariatric surgery, the overall T2DM remission and relapse rates were 61.4 per 1000 person‐months (95% confidence interval [CI] 56.8–66.4) and 5.7 per 1000 person‐months (95% CI 4.1–7.9), respectively. These rates were similar in the SG and OAGB groups. Multivariate hazard ratio analysis identified history of insulin therapy and T2DM duration prior to surgery as predictors of remission, while treatment with ≥2 glucose‐lowering agents was the only relapse predictor. Additionally, patients undergoing SG experienced either remission or relapse within a significantly shorter time frame compared to those undergoing OAGB.

Conclusion

After 5 years of follow‐up, there were no significant differences between the SG and OAGB groups with regard to T2DM remission and relapse. Bariatric surgery was less likely to result in remission in patients with a history of insulin therapy and longer durations of T2DM prior to surgery. Furthermore, patients who received ≥2 glucose‐lowering agents, despite possible remission, were at a higher risk of experiencing late relapse.
A weekly 4‐methylpyrazole treatment attenuates the development of non‐obese metabolic dysfunction‐associated steatotic liver disease (MASLD) in male mice: Role of JNK
Authors: Burger Katharina , Jung Finn , Staltner Raphaela , Csarmann Katja , Schweiger Kerstin , Brandt Annette , Baumann Anja , Scholda Julia , Kopp Florian , Bergheim Ina
Published: September 2024

Background

4‐methylpyrazole (4MP, fomepizole) is a competitive inhibitor of alcohol dehydrogenase (ADH) preventing the metabolism of ethylene glycol and methanol, respectively, into their toxic metabolites. 4MP seems also to possess a potential in the treatment of intoxication from other substance, for example, acetaminophen, and to modulate JNK‐dependent signalling. Here, we determined if a treatment with 4MP once weekly affects the development of diet‐induced non‐obese metabolic dysfunction‐associated steatotic liver disease (MASLD) in C57BL/6 mice.

Methods

Male C57BL/6 mice (6–8 weeks old, n = 7‐8/group) were pair‐fed either a liquid control diet (C) or a liquid sucrose‐, fat‐ and cholesterol‐rich diet (SFC) for 8 weeks while being concomitantly treated with 4MP (50 mg/kg bw i.p.) or vehicle once a week. Liver damage, inflammatory markers and glucose tolerance were assessed. Moreover, in endotoxin‐challenged J774A.1 cells pretreated with 4MP, pro‐inflammatory markers were assessed.

Results

The concomitant treatment of SFC‐fed mice with 4MP attenuated the increase in JNK phosphorylation and pro‐inflammatory markers like IFNγ, IL‐6 and 3‐nitrotyrosine protein adducts in liver tissue found in vehicle‐treated SFC‐fed mice, while not affecting impairments of glucose tolerance or the increase in portal endotoxin levels. Moreover, a pretreatment of endotoxin‐stimulated J774A.1 cells with 4MP significantly attenuated the increases in JNK phosphorylation and pro‐inflammatory mediators like IL‐6 and Mcp1.

Conclusions

Taken together, our results suggest that a treatment with 4MP once weekly attenuates the activation of JNK and dampens the development of non‐obese MASLD in mice.
Patterns of Ecological Specialisation Among Multiple Piscivorous Morphs of a Diverse Assemblage of Salvelinus Fishes
Authors: Esin Evgeny V. , Shkil Fedor N. , Shulgina Elena V. , Baskakova Yulia A. , Markevich Grigorii N.
Published: September 2024

Adaptive radiation is considered to be a major source of biodiversity in charrs of the genus Salvelinus. These fishes demonstrate numerous examples of diversification in postglacial lakes and rivers resulting in the emergence of different ecomorphs, including piscivorous. Usually, the number of fish feeders does not exceed two, suggesting the existence of ecological and/or internal factors that prevent further diversification. Under these circumstances, rare instances of increases in the number of piscivorous morphs are of particular interest. Here, we present a comprehensive study of the piscivorous charr assemblage in Lake Kronotskoe, residence of the most diverse species flock of Salvelinus fishes. To unravel the diversity and ecological relationships of piscivorous charrs, we analysed their morphology and microsatellite DNA polymorphism, distribution within the lake, trophic preferences and parasite load, as well as trace element accumulation, stable isotope and free fatty acid ratios. We revealed that, apart from a few strictly benthivorous morphs, the lake is inhabited by four closely related but morphologically and genetically distinct morphs that exhibit a range of piscivorous specialisation: from opportunistic secondary predation to ultra‐specialised primary piscivory. They effectively exploit the spatiotemporal structure of the ecosystem and experience diversifying selection due to niche discordance. Each piscivorous morph develops specific phenotypic, ecological and life history traits that allow it to terminate weakly overlapping branches of the trophic chain and share the energy flows of the lake ecosystem. Our data suggest that Lake Kronotskoe facilitates high level of ecological opportunity that favours niche expansion and allows the piscivorous lineage to simultaneously realise the archetypical modes of ecological diversification available to fishes in cold‐water freshwaters.
Factors Influencing the Selection of Dentistry as a Career Among Prospective Candidates: A Multicentre Cross‐Sectional Study
Authors: Abdul Hamid Nor Faharina , Jaafar Azlan , Asming Nurshafikah Nazirah , Suria Nurul Syafiqah , Ho Ting Khee , Lim Zhi Yin Joan , Lim Tong Wah
Published: September 2024

Objective

This study aimed to analyse the impact of sociodemographic factors on dental school candidates' decision to pursue dentistry as their career of choice.

Materials and Methods

Candidates shortlisted by three dental schools were invited to participate in a self‐administered questionnaire study, featuring a validated instrument containing sociodemographic questions and 16 motivational items grouped into four domains: economic, professional, vocational and personal background reasons. The variations in motivational item scores across sociodemographic factors were assessed using the Mann–Whitney U test (age, sex, ethnicity, having relatives in the dental profession and dentistry as the first choice) and Kruskal–Wallis test (dental school and family income).

Results

A total of 295 dental school candidates participated in the study (Universiti Teknologi MARA: 137; Universiti Kebangsaan Malaysia: 99; MAHSA University: 59). Approximately 95% of participants identified dentistry as their primary career choice, with the vocational motivation of ‘I like to help people’ being the most prominent motivational factor. Dental school emerged as the critical factor significantly influencing three quarters of the motivational items. Sex, ethnicity and having relatives in the dental profession were the remaining factors significantly associated with variations in certain motivational items. Both dental school and ethnicity significantly affected four motivational domains (economic, professional, vocational and personal background).

Conclusion

This study provides an insightful overview of the sociodemographic factors that impact career decision‐making among prospective dental students. The scores for most motivational items varied among shortlisted candidates in three dental schools. The findings hold implications for policy development in dentistry by universities and public policymakers.
How Does Perceived Social Support Influence Students’ Science Academic Outcomes? A Cross‐Sectional Study
Authors: Huangfu Qian , Luo Sisi , Huang Weilin , He Qianmei , Xia Zhenyang
Published: September 2024

Students’ perceived social support from important others may be an important protective factor in science self‐handicapping. This study examined the extent to which science self‐handicapping mediates the relationship between perceived social support and science academic outcomes (engagement and achievement). The study used a cross‐sectional survey design with self‐report data from 2654 participants in elementary schools and 2781 participants in high school from China. The results indicated that (1) perceived social support had an effect on students’ science academic engagement and achievement; (2) self‐handicapping in science mediated the entire process; (3) at different stages, different social support would not be equally important for the effects of adolescents’ self‐handicapping in science. The findings indicate that social support can create a positive academic environment to weaken the effect of self‐handicapping on students’ science academic outcomes, and educators need to consider the entire influence process differently in different academic stages of their students.
Hypothalamic cerebrospinal fluid‐contacting neurons project to the rostral agranular insular cortex: An immunofluorescence and ultrastructural analysis in the rat
Authors: Martínez‐Lorenzana Guadalupe , Gamal‐Eltrabily Mohammed , Palma‐Tirado Lourdes , González‐Hernández Abimael , Condés‐Lara Miguel
Published: September 2024

Cerebrospinal fluid‐contacting neurons (CSF‐cNS) are considered mechanoreceptors and chemoreceptors involved in detecting changes in CSF circulation. However, considering that recent data suggest that this type of cell could exert an active response when an external stimulus is sensed, identification of CSF‐cNS may be relevant. In this regard, some data suggest that a neuronal connection exists between the ventral region of the hypothalamic paraventricular nucleus (PVN) and rostral agranular insular cortex (RAIC); indeed, a potential CSF‐cNS is hypothesized. However, a detailed analysis of this connection has not been conducted. Thus, using neuronal tracers (Fluoro‐Gold® (FG) and cholera toxin (ChT)) coupled with transmission electron microscopy and immunofluorescence assays against Fluoro‐Gold®, oxytocin (OXT), vasopressin (AVP) and oxytocin receptors (OTR), we describe an oxytocinergic or vasopressinergic CSF‐cNS between the PVN and RAIC. Our results showed that CSF‐cNS along the PVN labelled with oxytocin and/or AVP were present in dendritic projections near the third ventricle. This CSF‐cNS in the PVN seems to project to the RAIC. Inside the RAIC, ultrastructural analysis showed that axons immunopositive for oxytocin from the PVN sustained synaptic connections with neurons that expressed OTR. These findings show that the CSF‐cNS from the PVN sends projections to the RAIC. To the best of our knowledge, the relevance of CSF‐cNS has not been elucidated; however, we hypothesized that the activation of cells could concomitantly release neuropeptides (i.e., oxytocin and AVP) in the CSF and RAIC. Thus, further analysis of the impact of neuropeptides released into the third ventricle and RAIC is warranted.
Child health and psychosocial wellness in the context of maternal role overload and depression
Authors: McIntosh Doneila L. , Trofholz Amanda , Tate Allan D. , Berge Jerica M.
Published: September 2024

Objective

The objective of this study was to examine the variability of child health and psychosocial outcomes in the context of maternal role overload and maternal depression.

Background

Role overload, characterized as time‐based role stress, is commonly linked to depression in mothers. However, it remains uncertain whether maternal role overload poses a risk for negative child health and wellness. Although maternal depression is a known risk factor for poor child health and psychosocial outcomes, the outcomes themselves often reveal variability.

Method

This study aimed to investigate the heterogeneity of child health and psychosocial outcomes using latent profile analyses. Multinomial logistic regression analyses were conducted to examine differences in profile membership based on the child's experiences of maternal role overload and depression. Data were from 1,172 mother–child dyads from the Family Matters study.

Results

The analyses unveiled four distinct profiles (i.e., moderate health/psychosocial wellness, poor health/moderate psychosocial wellness, struggling health/poor psychosocial wellness, thriving health/psychosocial wellness), each associated with varying levels of health and psychosocial wellness. Both maternal role overload and depression were found to heighten the risk of poor health and psychosocial wellness in children.

Conclusion

Children with struggling and poor health and psychosocial outcomes had higher odds of maternal depression and maternal role overload than children in the thriving profile. These findings suggest that maternal role overload is a potential risk to child health and psychosocial outcomes.

Implications

These findings emphasize the importance of continuous depression screening in mothers and the implementation of solution‐focused interventions targeting maternal role overload.
Structural insights into the recognition of purine‐pyrimidine dinucleotide repeats by zinc finger protein ZBTB43
Authors: Yang Yang , Zhang Shuting , Xu Li , Pan Yan , Xuan Yumi , Kai Yuanzhong , Chen Xuemin
Published: September 2024

Purine‐pyrimidine repeats (PPRs) can form left‐handed Z‐form DNA and induce DNA double‐strand breaks (DSBs), posing a risk for genomic rearrangements and cancer. The zinc finger (ZF) and BTB domain‐containing protein 43 (ZBTB43) is a transcription factor containing two Cys2‐His2 (C2H2) and one C3H1 zinc fingers and plays a crucial role in maintaining genomic and epigenomic integrity by converting mutagenic Z‐form PPRs to the B‐form in prospermatogonia. Despite its importance, the molecular mechanism underlying the recognition of PPRs by ZBTB43 remains elusive. In this study, we determined the X‐ray crystal structure of the ZBTB43 ZF1‐3 in complex with the B‐form DNA containing the CA repeats sequence. The structure reveals that ZF1 and ZF2 primarily recognize the CACA sequence through specific hydrogen‐bonding and van der Waals contacts via a quadruple center involving Arg389, Met411, His413, and His414. These interactions were further validated by fluorescence‐based DNA‐binding assays using mutated ZBTB43 variants. Our structural investigation provides valuable insights into the recognition mechanism of PPRs by ZBTB43 and suggests a potential role for ZBTB43 in the transformation of Z‐DNA to B‐DNA, contributing to the maintenance of genomic stability.
Divergent temporal responses of native macroinvertebrate communities to biological invasions
Authors: Soto Ismael , Macêdo Rafael L. , Carneiro Lais , Briski Elizabeta , Kouba Antonín , Cuthbert Ross N. , Haubrock Phillip J.
Published: September 2024

Biological invasions pose a major threat to biodiversity, ecosystem functioning, and human well‐being. Non‐native species can have severe ecological impacts that are transformative, affecting ecosystems across both short‐term and long‐term timescales. However, few studies have determined the temporal dynamics of impact between these scales, impeding future predictions as invasion rates continue to rise. Our study uses a meta‐analytical approach to dissect the changing taxonomic and functional impacts of biological invasions on native macroinvertebrate populations and communities in freshwater ecosystems across Europe, using a recently collated European long‐term time series spanning several decades. Our findings reveal a complex temporal pattern: while initial stages of invasions (i.e. five years after the first record of non‐native species) often exhibited benign impacts on macroinvertebrate abundance, richness, or functional diversity, the long‐term (i.e. the period following the early invasion) effects became predominantly negative. This pattern was consistent between taxonomic and functional metrics for impacts at both the population and species level, with taxonomic metrics initially positively affected by invasions and functional metrics being more stable before also declining. These results suggest that even initially benign or positively perceived impacts could be eventually superseded by negative consequences. Therefore, understanding the magnitude of invasion effects increasingly requires long‐term studies spanning several years or decades to offer insights into effective conservation strategies prioritising immediate and future biodiversity protection efforts. These findings also highlight the importance of integrating multiple taxonomic, functional and temporal components to inform adaptive management approaches to mitigate the negative effects of current and future biological invasions.
A placebo controlled, randomized clinical trial of galcanezumab for vestibular migraine: The INVESTMENT study
Authors: Sharon Jeffrey D. , Krauter Roseanne , Chae Ricky , Gardi Adam , Hum Maxwell , Allen Isabel , Levin Morris
Published: September 2024

Objective

To study if galcanezumab is effective for vestibular migraine (VM).

Background

There are currently no placebo‐controlled trials showing that treatment is effective for VM. Therefore, we performed the first placebo controlled, randomized clinical trial of a calcitonin gene–related peptide–targeted monoclonal antibody for VM.

Methods

This was a single site, prospective, double‐blind placebo controlled randomized clinical trial. Key inclusion criteria were as follows: participants aged 18–75 years with a diagnosis of VM or probable VM per Barany Society criteria. The primary outcome was change in VM‐PATHI (Vestibular Migraine Patient Assessment Tool and Handicap Inventory) score, and secondary outcomes included change in DHI (Dizziness Handicap Inventory) score, and count of definite dizzy days (DDDs). Participants were randomized 1:1 to 3 months of treatment with galcanezumab or placebo via subcutaneous injection with a pre‐filled syringe, 240 mg the first month, and 120 mg for the second and third months.

Results

Forty participants were randomized, and 38 participants were in the modified intent to treat analysis. VM‐PATHI score was reduced 5.1 points (95% confidence interval [CI] −13.0 to 2.7) for placebo (N = 21), and 14.8 points (95% CI −23.0 to −6.5) for galcanezumab (N = 17), a difference of −9.6 (95% CI −20.7 to 1.5, p = 0.044). DHI dropped 8.3 points in the placebo arm (95% CI −15.0 to 1.6), and 22.0 points in the galcanezumab arm (95% CI −31.9 to −12.1), a difference of −13.7 (95% CI −20.4 to −8.5, p = 0.018). The count of DDDs per month dropped from 18 days (standard deviation [SD] 7.6) in the baseline month to 12.5 days (SD 11.2) in month 4 for those in the placebo arm, and from 17.9 days (SD 7.9) in the baseline month to 6.6 days (SD 7.3) in month 4 for those in the galcanezumab arm, a difference of −5.7 days (95% CI −10.7 to −0.7, p = 0.026). No serious adverse events were observed.

Conclusions

In this pilot study, galcanezumab was effective in treating VM.
Efficacy of galcanezumab in proline‐rich transmembrane protein 2 (PRRT2)‐associated familial hemiplegic migraine: A case series
Authors: Sottani Costanza , Di Lazzaro Giulia , Calabresi Paolo , Pomponi Maria Grazia , Tiziano Francesco Danilo , Bentivoglio Anna Rita , Servidei Serenella , Vollono Catello
Published: September 2024

Background

Familial hemiplegic migraine (FHM) is a rare subtype of migraine with aura. Variants in calcium voltage‐gated channel subunit alpha1 A (CACNA1A), ATPase Na+/K+ transporting subunit alpha 2 (ATP1A2), and sodium voltage‐gated channel alpha subunit 1 (SCN1A) genes have a well‐established association with the development of FHM. Recent studies suggest that other genes may also have a significant role in the pathogenesis of FHM, including proline‐rich transmembrane protein 2 (PRRT2). To our knowledge, there are currently no documented reports of the use of monoclonal antibodies targeting calcitonin gene‐related peptide in FHM caused by a specific identified genetic mutation – and in particular not in FHM associated with PRRT2 mutations. The aim of our work is to describe the efficacy of galcanezumab as a prophylaxis treatment on patients from an Italian family consisting of six patient carriers of a PRRT2 pathogenic variant.

Methods

Inclusion criteria for treatment eligibility consisted of a confirmed diagnosis of genetically confirmed FHM as defined by the International Classification of Headache Disorders, third edition, number of headache days/month ≥4, and at least two previously failed migraine prophylaxis treatments. We evaluated clinical data of patients treated with galcanezumab regarding number of headache days/month, frequency of aura, disability caused by HM using the Migraine Disability Assessment (MIDAS), attack severity through a numerical rating scale (NRS), acute medications intake, and response to acute medications at baseline (t0) and after 3 (t1) and 6 (t2) months of treatment.

Results

Three out of six family members met inclusion criteria for treatment with galcanezumab. The average number of headache days/month, acute medications, and MIDAS significantly decreased in all treated patients, as well as the average NRS score. Aura frequency reduced by ≥50% compared to the baseline in all three patients. No adverse events related to galcanezumab were reported.

Conclusion

Galcanezumab is a valid and well‐tolerated treatment option in PRRT2‐associated FHM.
Effect of the membrane processing on tannin removal from soluble fraction of Persian gum
Authors: Akbarzadeh Anahita , Mirsaeedghazi Hossein , Azarikia Fatemeh
Published: September 2024

Tannins, which are known as anti‐nutrient compounds with capability of limiting proteins and minerals bioavailability, are present in Persian gum. Ultrafiltration (UF, polysulfone membrane, 30 and 90 kDa, 1, 2 and 5 bar) and nanofiltration (NF, polysulfone, 400 Da, 2.5 and 5 bar) were used to remove tannin from the soluble fraction of Persian gum. The results revealed that the highest amount of tannin removal was achieved in UF (5 bar) and NF (5 bar). However, the use of the membrane process significantly decreased the apparent viscosity of the permeate, which might have an undesirable effect on the functionality of the gum. The effects of membrane molecular weight cut‐off, feed temperature, ultrasound pre‐treatment, feed concentration and pH, on the amount of tannic acid reduction, and changes in permeate flux, volume concentration factor difference, tannin reduction efficiency, and permeate apparent viscosity were evaluated. The results showed that total tannin removal efficiency was increased by ultrasound pre‐treatment, reduction of feed pH, and higher membrane molecular weight cut‐off. Increasing the feed temperature and concentration enhanced the apparent viscosity of permeate, although its value was lower than the control sample.
Managing Challenging Behaviour in the Adolescent Inpatient Environment
Authors: Zuccala Matteo , Kielich Roman , O'Keefe Sophie , Webb Shannon
Published: September 2024

Frontline clinical staff, typically nurses, are routinely faced with the dilemma of managing challenging, defiant and sometimes unsafe behaviours. Structures of ward rules, regulations and ‘behavioural expectations’ are often employed in hospital environments in service of regulating these behaviours and ensuring collective well‐being. Adolescent inpatient populations, however, pose unique and particularly complex challenges for managing behavioural expectations, given the unique needs and inherent tempestuousness of this developmental period. This article presents a critical review of the existing literature on behavioural expectations for inpatient units, which is largely bereft of adolescent‐specific guidelines. Relevant theoretical perspectives are examined that lend understanding to the management of adolescent behaviour. Finally, drawing from neurodevelopmental, attachment and socio‐evolutionary theory, guiding clinical principles and recommendations are derived for best practice in managing challenging adolescent behaviour in hospital settings.
The impact of Malta's Tapering of Benefits scheme on employment outcomes
Authors: Sant Kurt
Published: September 2024

This article analyses the Tapering of Benefits scheme introduced in Malta in 2014, aimed at unlocking the poverty trap stalemate. Survival analysis and Cox proportional hazard models are employed to analyse the impact that the scheme has had on the job‐finding rate and the chances of retaining employment once individuals who were previously on benefits find a job. The analyses are based on high‐quality national data on the whole population of beneficiaries and their employment histories. The results show that the scheme doubles the job‐finding probability, whilst the chance of job termination drops by 11.8 percentage points for eligible individuals. Furthermore, the scheme's impact once it finally tapers out is not different from the first 36 months, showing that its impact is robust in the medium term.
An approach to reducing early kidney transplant failure by flow cytometry crossmatching
Authors: Cook Daniel J. , Terasaki Paul I. , Iwaki Yulcbi , Terashita Glenn V. , Lau Marie
Published: September 2024

A relationship between kidney transplants that did not function during the 1st month posttranpslant, and a positive T‐cell flow cytometry crossmatch (FCXM), was observed in a retrospective study of 231 cadaver donor transplants. Overall, FCXM‐positive grafts (23%) had a 33% 1‐month nonfunction rate compared to 8% if the FCXM was negative (p = 0.00004). If only sensitized patients had been studied (regrafts and peak antibody‐positive patients), 16 of 17 (94%) of the FCXM‐associated nonfunctional grafts would have been identified. No association between the FCXM and early transplant outcome was seen with nonsensitized patients (63% of the total). Had the FCXM been utilized prospectively in this series, one‐half (16 of 32) of the grafts that did not function would not have been performed. We provide here a practical protocol by which the FCXM can be used on a routine basis.
Gastroduodenal complications after renal transplantation: The role of prophylactic gastric surgery in hyperacid kidney allograft recipients
Authors: Bansky G. , Do U. Huynh , Largiadèr F. , Binswanger U.
Published: September 2024

During an 8‐year period ending on 31 December 1984 prophylactic gastric surgery was performed in 121 of 508 renal allograft recipients. Acid hypersecretion was the sole indication for the vagotomy and pyloroplasty in 53 patients (43%). After renal transplantation, gastroduodenal complications occurred in 7.9% of the total population, in 7.2% in the normacid group and in 16.7% of the hyperacid patients not subjected to prophylactic gastric surgery (p = 0.04). Prophylactic surgery in the hyperacid group reduced the incidence of such complications to 7.5%; however, this improvement was not significant. Assessment of factors associated either with increased risk of, or protection from, stress ulcers revealed that patients with gastroduodenal complications received antacids significantly less often than matched controls. If all hyperacid patients had undergone prophylactic surgery, the calculated rate of gastroduodenal complications could be reduced by only 1%. Therefore, routine screening for acid hypersecretion in patients awaiting renal transplantation seems not to be justified. In contrast, consequent administration of antacids appears to be an effective measure, reducing the incidence of gastroduodenal complications after renal transplantation.
Successful transplantation of 50 single unit pediatric kidneys ages 11 to 48 months into adult recipients
Authors: Jacoby Karny , Lippman Howard R. , Hura Claudia E. , McFarlin Linda , Jones Cathy F. , Banowsky Lynn H.
Published: September 2024

There is currently an imbalance between the need for cadaveric kidneys for transplantation and the supply. The medical criteria for accepting cadaveric donors are changing and organs that were originally thought to be unacceptable have functioned well. Previous reports have discussed the problems with transplanting pediatric allografts less than 4 years old into adult recipients, and the results have not been encouraging. From 1986 to 1991 a total of 50 kidneys ages 11 to 48 months were transplanted as single units into adult recipients (Group A). Ninety‐one adult donor cadaveric transplants were used as controls (Group B). The cadaveric transplants were 2nd or 3rd transplants in 7 of the Group A and 12 of the Group B patients. Renal preservation, storage times, and demographics were the same. Prednisone, cyclosporine, and either Minnesota ALG or OKT3 were used for immunosuppression in both groups. Imuran was added in immunologically high‐risk patients. The 1‐year actuarial patient and allograft survivals for Group A versus Group B were 89.5% versus 94.2% (p = 0.49) and 71.3% versus 87.8% (p=0.01). respectively. There was no difference in allograft or patient survival in kidneys from donors 11–24 months of age or 25‐48 months (p=0.56). Renal growth, as measured by sonography, occurred while on cyclosporine A. Excretory and hormonal function as measured by creatinine and hematocrit both improved. Seventy percent of the Group A patients and 76% of the Group B patients were free from rejection in the first 2 months post transplantation (p = 0.45). This is the largest single center scries using single renal units from donors less than 48 months old and demonstrates that pediatric cadaveric transplantation is both technically and physiologically feasible and that allograft and patient survival are acceptable. The subgroups within Group A of donors aged 11–24 and 25‐48 months do equally well. Excretory, hormonal function, and renal growth were excellent on cyclosporine A therapy.
Unusual manifestations of tuberculosis in cyclosporine‐treated renal transplant recipients
Authors: Wong Linda L. , Levin Barry S. , Collins Geoffrey M. , Bry William I.
Published: September 2024

Tuberculosis has been observed to occur with a higher frequency in renal transplant recipients compared with the general population. This retrospective review of tuberculosis in cyclosporine‐treated renal transplant recipients over the past 5 years was conducted to evaluate the incidence of the disease, its common manifestations and the efficacy of treatment. Medical record review was carried out to identify recipients of renal transplants who were treated for tuberculosis over the past 5 years. Five patients were identified. Their case reports constitute the substance of this review. The incidence of tuberculosis in our population of renal transplant recipients is approximately 0.5%. Manifestations of the disease which are apparent in all 5 cases include extrapulmonary manifestations of the infection, delay of at least a year in the development of tuberculosis from the time of transplantation and, finally, prior immigration by the patients to the United States from foreign countries in which tuberculosis is more prevalent. We conclude that tuberculosis continues to complicate renal transplantation in the cyclosporine era. A high index of suspicion for this disease should be exercised when evaluating patients with evidence of pulmonary and extrapulmonary infections, especially in the late post‐transplant period.
OKT3 for induction of immunosuppression and treatment of rejection in cardiac allograft recipients
Authors: Renlund Dale G.
Published: September 2024

Following the initial reports in 1987 of the successful use of OKT3 in cardiac transplantation, a number of studies utilizing OKT3 for induction of immunosuppression and treatment of acute rejection have further confirmed its efficacy in the treatment of cardiac allografts. In clinical trials comparing OKT3 induction to conventional triple‐agent therapy with cyclosporine, azathioprine, and corticosteroids, OKT3 yielded significantly longer times to first rejection and lower percentages of patients with rejections in the 1st month following transplantation, even though, in the nonrandomized trials, OKT3 treatment was reserved for more high‐risk patients. In a number of studies comparing OKT3 to polyclonal antithymocyte globulins (ATG), OKT3 induction was followed by fewer rejection episodes/patient and a longer time to 1st rejection episode, although some trials reported more favorable results with ATG. The use of OKT3 for induction was shown to facilitate the withdrawal of maintenance corticosteroid therapy in significantly more patients than did ATG induction. Investigations give support to a 14‐day induction regimen with OKT3 in cardiac transplant recipients. Studies have shown successful retreatment with OKT3 following its use for induction and have indicated that low antibody titers are obtained with its initial use in most studies. Rescue treatment with OKT3 for acute rejection has successfully reversed rejection in a significantly higher percentage of patients than ATG. In one small trial, primary therapy with OKT3 reversed rejections in 100% of patients. As in other organ studies, first‐dose reactions accompanied the treatment of cardiac allografts in a majority of OKT3‐treated patients. A high incidence of lymphoproliferative disorder reported in one trial has not been replicated in other trials. Infection rates following OKT3 induction or treatment of rejection appeared to be similar to those following polyclonal antilymphocyte antibodies or standard triple‐drug therapy, although the incidence of infections varied considerably from investigation to investigation.
Successful identification of acute renal allograft rejection with duplex ultrasonography
Authors: Gifford Robert R. M. , Neumyer Marsha M. , Yang Harold C. , Escobar Francisco S. , Thiele Brian L.
Published: September 2024

Duplex ultrasonography has met with variable accuracy in identifying acute renal allograft rejection. These published studies have focused on using mathematical indices. We have applied duplex ultrasonography differently by insonating the site of rejection, i.e. renal cortex, to identify by subjective analysis the changes of the velocity spectral patterns. This subjective analysis method was compared to the mathematical indices of diastolic/systolic ratio and pulsatility index in 126 episodes of clinical acute renal allograft rejection which all had biopsy correlation. This present study represents the largest published experience with duplex ultrasonography and renal transplant rejection. Subjective analysis of velocity spectral patterns (SUBJ) resulted in sensitivity of 87%, specificity of 94% and overall accuracy of 88%. This technique was statistically better than the diastolic/systolic ratio (DSR) sensitivity of 40%, specificity of 72% and overall accuracy of 49%, or the pulsatility index (PI) sensitivity of 47%, specificity of 75% and overall accuracy of 55%. The superior results of the subjective analysis technique of duplex ultrasonography to identify acute renal allograft rejection suggests that this diagnostic approach has sufficient accuracy to avoid invasive allograft biopsies.
Circulating serum levels of soluble CD23 (sCD23) after renal transplantation
Authors: Traindl Otto , Gisinger Christoph , Reading Susan , Rosenkranz Alexander R. , Zlabinger Gerhard J.
Published: September 2024

In the present study the role of sCD23 determination in the management of renal graft recipients during the early postoperative period has been evaluated. In the majority of patients, increases in sCD23 serum levels were observed up to 3 days before the manifestation of an acute rejection (in 82% of cases) or infection episode (in 73% of cases), but no discrimination between these two clinical events was possible. This rise in sCD23 levels was significantly more pronounced than fluctuations observed in patients with uncomplicated courses or with graft dysfunction due to acute tubular necrosis. Serum levels of sCD23 were not influenced by excretory kidney function. These findings indicate that, in addition to its reflecting B‐cell function, sCD23 may also play a role in immunological processes involving T cells and/or monocytes, thus indicating a broader range of activity of this cytokine‐like molecule than has been previously assumed.
Post‐transplant changes of segment 4 after living related liver transplantation
Authors: Cheng Yu Fan , Chen Chao Long , Haung Tung Liang , Lee Tze Yu , Chen Tai Yi , Chen Yaw Sen , Liu Po Ping , Chiang Yuan Cheng , Eng Hock Liew , Wang Chih Chi , Cheung Hok Kim , Jawan Bruno , Goto Shigeru
Published: September 2024

The purpose of this study was to evaluate the outcome of the medial segment of the graft after living related liver transplantation (LRLT). Of the 12 pediatric recipients who underwent LRLT, 2 received whole left liver graft, 1 left lateral segment graft, and 9 extended left lateral segment grafts. The hepatic veins of the donor were reviewed and the volume of the medial segment and left lateral liver was measured before and 6 months after liver transplantation. The flow velocity and direction of the portal vein in the medial segment graft was also evaluated by Doppler ultrasound. The grafted livers of all recipients showed a substantial increase in volume of 9‐120% 6 months after LRLT. For the left lateral segment, an increase in volume was found in all cases ranging from 21 to 245%. For the medial segment, volume increases of 5‐48% were found in seven cases with normal hepatopetal flow detected inside the segment 4 intrahepatic portal vein. In four cases, the partial medial segment graft of the extended left lateral liver graft decreased in volume from 33 to 69%. Among these four cases, slow flow (n = 2) and hepatofugal flow (n = 1) were also detected in the intrahepatic portal vein of the medial segment. Mapping of the tributary of the hepatic veins of the graft revealed inadequate venous drainage of the partial segment 4 graft, which may be considered as the cause of the atrophic change of the partial segment 4 graft. In conclusion, different regenerative rates between the left lateral segment and the medial segment were noted, with a greater rate in the left lateral segment. The venous drainage of the medial segment is of primary concern in the determination of the outcome of the regeneration. Atrophic change occurs when inadequate hepatic venous drainage is encountered. Therefore, if an extended left lateral liver graft is required, the corresponding draining veins of the partial medial segment must be preserved. Otherwise, whole left liver or left lateral segment graft would be a better choice.