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The Rfam database, a widely used repository of non-coding RNA families, has undergone significant updates in release 15.0. This paper introduces major improvements, including the expansion of Rfamseq to 26 106 genomes, a 76% increase, incorporating the latest UniProt reference proteomes and additional viral genomes. Sixty-five RNA families were enhanced using experimentally determined 3D structures, improving the accuracy of consensus secondary structures and annotations. R-scape covariation analysis was used to refine structural predictions in 26 families. Gene Ontology (GO) and Sequence Ontology annotations were comprehensively updated, increasing GO term coverage to 75% of families. The release adds 14 new Hepatitis C Virus RNA families and completes microRNA family synchronization with miRBase, resulting in 1603 microRNA families. New data types, including FULL alignments, have been implemented. Integration with APICURON for improved curator attribution and multiple website enhancements further improve user experience. These updates significantly expand Rfam's coverage and improve annotation quality, reinforcing its critical role in RNA research, genome annotation and the development of machine learning models. Rfam is freely available at https://rfam.org., (© The Author(s) 2024. Published by Oxford University Press on behalf of Nucleic Acids Research.)

Phosducin-like proteins (PhLP) are thioredoxin domain-containing proteins that are highly conserved across unicellular and multicellular organisms. PhLP family proteins are hypothesized to function as co-chaperones in the folding of cytoskeletal proteins. Here, we present the initial molecular, biochemical, and functional characterization of CG4511 as Drosophila melanogaster PhLP3. We cloned the gene into a bacterial expression vector and produced enzymatically active recombinant PhLP3, which showed similar kinetics to previously characterized orthologues. A fly strain homozygous for a P-element insertion in the 5' UTR of the PhLP3 gene exhibited significant downregulation of PhLP3 expression. We found these male flies to be sterile. Microscopic analysis revealed altered testes morphology and impairment of spermiogenesis, leading to a lack of mature sperm. Among the most significant observations was the lack of actin cones during sperm maturation. Excision of the P-element insertion in PhLP3 restored male fertility, spermiogenesis, and seminal vesicle size. Given the high level of conservation of PhLP3, our data suggests PhLP3 may be an important regulator of sperm development across species., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Petit et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Medication adjustments in Parkinson's disease (PD) are driven by patient subjective report and clinicians' rating of motor feature severity (such as bradykinesia and tremor)., Objective: As patients may be seen by different clinicians at different visits, this study aims to determine the inter-rater reliability of upper limb motor function assessment among clinicians treating people with PD (PwPD)., Methods: PwPD performed six standardised hand movements from the Movement Disorder Society's Unified Parkinson's Disease Rating Scale (MDS-UPDRS), while two cameras simultaneously recorded. Eight clinicians independently rated tremor and bradykinesia severity using a visual analogue scale. We compared intraclass correlation coefficient (ICC) before and after a training/calibration session where high-variance participant videos were reviewed and MDS-UPDRS instructions discussed., Results: In the first round, poor agreement was observed for most hand movements, with best agreement for resting tremor (ICC 0.66 bilaterally; right hand 95 % CI 0.50-0.82; left hand: 0.50-0.81). Postural tremor (left hand) had poor agreement (ICC 0.14; 95 % CI 0.04-0.33), as did wrist pronation-supination (right hand ICC 0.34; 95 % CI 0.19-0.56). In post-training rating exercises, agreements improved, especially for the right hand. Best agreement was observed for hand open-close ratings in the left hand (ICC 0.82, 95 % CI 0.64-0.94) and resting tremor in the right hand (ICC 0.92, 95 % CI 0.83-0.98). Discrimination between right and left hand features by raters also improved, except in resting tremor (disimprovement) and wrist pronation-supination (no change)., Conclusions: Clinicians vary in rating video-recorded PD upper limb motor features, especially bradykinesia, but this can be improved somewhat with training., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

The recent advent of highly effective anti-obesity medications (AOM) provides pediatric clinicians a powerful tool to augment the treatment of obesity and improve outcomes. The 2023 American Academy of Pediatrics guidelines state clinicians "should offer adolescents 12 years and older with obesity weight loss pharmacotherapy, according to medication indications, risks, and benefits, as an adjunct to health behavior and lifestyle treatment". This article will provide an update on the integration of AOM into practice, emphasizing clinical pearls and practical tips., Competing Interests: Disclosures Dr B. Sweeney consults without compensation for Nestle, Eli Lilly, Novo Nordisk, and Rhythm. She is an unpaid speaker for Rhythm. She is a paid investigator for Rhythm on 2 research studies. Dr W.P. Dutton, Dr N. Paddu, and Dr A. Braddock have no financial disclosures or conflicts of interest to report., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The Rfam database, a widely-used repository of non-coding RNA (ncRNA) families, has undergone significant updates in release 15.0. This paper introduces major improvements, including the expansion of Rfamseq to 26,106 genomes, a 76% increase, incorporating the latest UniProt reference proteomes and additional viral genomes. Sixty-five RNA families were enhanced using experimentally determined 3D structures, improving the accuracy of consensus secondary structures and annotations. R-scape covariation analysis was used to refine structural predictions in 26 families. Gene Ontology and Sequence Ontology annotations were comprehensively updated, increasing GO term coverage to 75% of families. The release adds 14 new Hepatitis C Virus RNA families and completes microRNA family synchronisation with miRBase, resulting in 1,603 microRNA families. New data types, including FULL alignments, have been implemented. Integration with APICURON for improved curator attribution and multiple website enhancements further improve user experience. These updates significantly expand Rfam's coverage and improve annotation quality, reinforcing its critical role in RNA research, genome annotation, and the development of machine learning models. Rfam is freely available at https://rfam.org., Competing Interests: Conflict of interest AB is a member of the Nucleic Acids Research Editorial Board.

Background: Factors related to clinically meaningful outcomes for pediatric patients seeking care for severe obesity are not well known. Examining patient-level and program-level characteristics related to success may inform future care. Objectives : To determine factors associated with a clinically significant reduction in weight status measured by %BMIp95 after 6 months of treatment. Study Design: This is a retrospective study of youth 5-17 years of age seeking multicomponent weight management care to determine if patient characteristics, treatment recommendations, reported adherence, and additional program-affiliated class participation are associated with 6-month change in %BMIp95. Results: Among 170 children with obesity, higher reductions in %BMIp95 were seen in those with medium-high dietary adherence compared to low-none (-10.8 vs. -4.0, p  = 0.002). Post hoc analysis showed higher dietary adherence among those with private insurance than public insurance (59% vs. 41%, respectively, p  = 0.04). Conclusion: Children receiving multidisciplinary multicomponent weight management, who achieve clinically meaningful outcomes, are more likely to be adherent to dietary recommendations regardless of the type. Further study is needed of how best to address social determinants of health to improve dietary adherence. Clinical Trial Registration Number: NCT02121132.

Continuously secreted by all cell types, extracellular vesicles (EVs) are small membrane-bound structures which shuttle bioactive cargo between cells across their external environment. Their central role as natural molecular messengers and ability to cross biological barriers has garnered significant attention in the use of EVs as therapeutic delivery vehicles. Still, harnessing the potential of EVs is faced with many obstacles. A cell line engineering approach can be used to exploit EVs to encapsulate a bespoke cargo of interest. However, full details regarding native EV-loading mechanisms remain under debate, making this a challenge. While Chinese hamster ovary (CHO) cells are well known to be the preferred host for recombinant therapeutic protein production, their application as an EV producer cell host has been largely overlooked. In this study, we engineered CHO DG44 cells to produce custom EVs with bespoke cargo. To this end, genetic constructs employing split green fluorescent protein technology were designed for tagging both CD81 and protein cargoes to enable EV loading via self-assembling activity. To demonstrate this, NanoLuc and mCherry were used as model reporter cargoes to validate engineered loading into EVs. Experimental findings indicated that our custom EV approach produced vesicles with up to 15-fold greater cargo compared with commonly used passive loading strategies. When applied to recipient cells, we observed a dose-dependent increase in cargo activity, suggesting successful delivery of engineered cargo via our custom CHO EVs., (© 2024 The Author(s). Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

Background: Central venous oxygen saturation (ScvO2) obtained from a central venous catheter (CVC) is often used to approximate oxygen delivery in critically ill patients. Despite their importance in administering medications and monitoring oxygen delivery, the use of CVCs can be associated with significant complications. Midline catheters are inserted via a peripheral vein above the antecubital fossa and provide a safe alternative to CVCs. This study aimed to determine the equivalence of ScvO2 and midline catheter oxygen saturation (SmO2) in critically ill patients., Methods: This was a single-center observational study of critically ill adult patients who had concurrently placed CVCs (internal jugular and subclavian) and midline catheters as part of standard ICU care. Venous oxygen saturation and lactate levels were measured from both catheters using the Abbott point-of-care i-STAT analyzer. Demographic and ICU admission data were collected. Continuous variables were compared using the paired t-test. Pearson's correlation was used to evaluate the linear correlation between ScvO2 and SmO2. The systematic error (bias) was calculated using Bland-Altman analysis. Receiver operating characteristic curves were constructed to evaluate the sensitivities and specificities for different values of SmO2 to predict ScvO2., Results: Forty-eight patients (n = 48) were enrolled in the study. The mean ScvO2 and SmO2 were 65.5% +/- 11.2% and 62.7% +/- 17.6% respectively (p = 0.1197). In the Bland-Altman analysis, the mean bias between ScvO2 and SmO2 was 2.8% +/- 12.3% with 95% limits of agreement of -21.3% to 26.9%. More than 60% of the ScvO2 and SmO2 values diverged by ≥ 5%., Conclusions: The difference between the mean SmO2 and ScvO2 was not statistically significant and the mean bias between SmO2 and ScvO2 is low. Despite this, the substantially large standard deviation and limits of agreement preclude the use of SmO2 as a direct surrogate of ScvO2., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Hepatitis C virus (HCV) is a plus-stranded RNA virus that often chronically infects liver hepatocytes and causes liver cirrhosis and cancer. These viruses replicate their genomes employing error-prone replicases. Thereby, they routinely generate a large 'cloud' of RNA genomes (quasispecies) which-by trial and error-comprehensively explore the sequence space available for functional RNA genomes that maintain the ability for efficient replication and immune escape. In this context, it is important to identify which RNA secondary structures in the sequence space of the HCV genome are conserved, likely due to functional requirements. Here, we provide the first genome-wide multiple sequence alignment (MSA) with the prediction of RNA secondary structures throughout all representative full-length HCV genomes. We selected 57 representative genomes by clustering all complete HCV genomes from the BV-BRC database based on k-mer distributions and dimension reduction and adding RefSeq sequences. We include annotations of previously recognized features for easy comparison to other studies. Our results indicate that mainly the core coding region, the C-terminal NS5A region, and the NS5B region contain secondary structure elements that are conserved beyond coding sequence requirements, indicating functionality on the RNA level. In contrast, the genome regions in between contain less highly conserved structures. The results provide a complete description of all conserved RNA secondary structures and make clear that functionally important RNA secondary structures are present in certain HCV genome regions but are largely absent from other regions. Full-genome alignments of all branches of Hepacivirus C are provided in the supplement., (© 2024. The Author(s).)

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details assessment and management of the child with overweight or obesity. The term "child" is defined as the child between 2 and 12 years of age. Because children are in a continual state of development during this age range, we will specify when our discussion applies to subsets within this age range. For the purposes of this CPS, we will use the following definitions: overweight in the child is a body mass index (BMI) ≥ 85th and <95th percentile, obesity in the child is a BMI ≥95th percentile, and severe obesity is a BMI ≥120% of the 95th percentile., Methods: The information and clinical guidance in this OMA Clinical Practice Statement are based on scientific evidence, supported by medical literature, and derived from the clinical perspectives of the authors., Results: This OMA Clinical Practice Statement provides an overview of prevalence of disease in this population, reviews precocious puberty in the child with obesity, discusses the current and evolving landscape of the use of anti-obesity medications in children in this age range, discusses the child with obesity and special health care needs, and reviews hypothalamic obesity in the child., Conclusions: This OMA Clinical Practice Statement on the child with obesity is an evidence based review of the literature and an overview of current recommendations. This CPS is intended to provide a roadmap to the improvement of the health of children with obesity, especially those with metabolic, physiological, psychological complications and/or special healthcare needs. This CPS addresses treatment recommendations and is designed to help the clinician with clinical decision making., Competing Interests: Authors of this Clinical Practice Statement received no payment for their writing, editing, and publishing work. While listed journal Editors received payment for their roles as Editors, they did not receive payment for their participation as authors.Suzanne Cuda: Rhythm Gold panel, Rhythm Advisory Board. Marisa Censani: none. Valerie O'Hara: Novo Nordisk speaker: telehealth conference 2023. Jennifer Paisley: Rhythm Pharmaceuticals speakers bureau. Roohi Kharofa: Rhythm Pharmaceuticals: EMANATE trial. Rushika Conroy: GOLD academy faculty for Rhythm Pharmaceuticals. Brooke Sweeney: Rhythm Pharmaceutical: Speaker, Consultant, BEAM Project, and Research support; no financial support; Consulting Novo Nordisk, past consultant Nestle Corp. and Eli Lilly. Cristina Fernandez: Rhythm Pharmaceutical: Council HPS and BEAM Project, No financial compensation. Meredith Dryer: none. Nancy T. Browne: none., (© 2024 The Authors.)

Objectives: Pediatric obesity remains a public health crisis in the United States, exacerbated by the COVID-19 pandemic. There are recommended guidelines for multidisciplinary care, but they remain challenging to implement, even in tertiary care weight management programs. The aim of this analysis is to describe the implementation of these recommendations among four pediatric weight management programs in the United States., Methods: This report capitalizes on a convenience sample of programs participating in the Stay In Treatment (SIT) Study, a multicenter study to address attrition among pediatric weight management programs in tertiary care, academic institutions in diverse geographic locations. The programs were compared regarding structure, program offerings, and funding support., Results: The four programs were interdisciplinary, offered individual and group treatment options, and were family-based. A range of clinicians provided interventions with nutrition, physical activity, behavioral and psychosocial components. Anti-obesity pharmacotherapy and bariatric surgery were offered, when appropriate. None of the programs were self-sustaining; they required institutional and philanthropic support to provide recommended, comprehensive treatment., Conclusions: Ongoing state and national advocacy are needed in the US to create consistent coverage for private and public insurance plans, so that high-risk children can have access to recommended treatment., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

We present three cases of posterior wall acetabulum fractures occurring in pediatric patients with open triradiate cartilage for whom preoperative magnetic resonance imaging was obtained and open reduction and internal fixation was done. All patients had excellent outcomes at an average of 68-week follow-up. Failure to adequately recognize the severity of pediatric acetabulum fractures can lead to detrimental long-term sequelae in acetabular development when treated nonsurgically. Management of this rare injury is not well reported in the literature. We highlight the utility of MRI in evaluating potential nonosseous injury and examining the articular surface to guide surgical management., (Copyright © 2024 The Authors. Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Orthopaedic Surgeons.)

Importance: Malaria transmission by Anopheles gambiae mosquitoes is very effective, in part because the parasite expresses a surface protein called Pfs47 that allows it to evade the mosquito immune system. Here we investigate how this protein changes the response of mosquito midgut epithelial cells to invasion by the parasite. Pfs47 is known to interact with P47Rec, a mosquito midgut receptor. We found that Pf47Rec inhibits caspase-mediated apoptosis by interacting with the Hsc70-3. This disrupts nitration of midgut epithelial cells invaded by the parasite and the release of hemocyte-derived microvesicles, which are critical for effective activation of the mosquito complement system that eliminates the parasite., Competing Interests: The authors declare no conflict of interest.

Background: This Obesity Medicine Association (OMA) Clinical Practice Statement (CPS) details special considerations for the management of the adolescent with obesity. The information in this CPS is based on scientific evidence, supported by medical literature, and derived from the clinical experiences of members of the OMA., Methods: The scientific information and clinical guidance in this CPS are based on scientific evidence, supported by the medical literature, and derived from the clinical perspectives of the authors., Results: This OMA Clinical Practice Statement addresses special considerations in the management and treatment of adolescents with overweight and obesity., Conclusions: This OMA Clinical Practice Statement on the adolescent with obesity is an overview of current recommendations. These recommendations provide a roadmap to the improvement of the health of adolescents with obesity, especially those with metabolic, physiological, and psychological complications. This CPS also addresses treatment recommendations and is designed to help the provider with clinical decision making., (© 2023 The Authors.)

Background: Acute appendicitis is the most common surgical emergency in children. Eighty percent of paediatric appendicectomies are performed by adult general surgeons on an annual basis. The remaining 20% are performed at Children's Health Ireland (CHI) centres. Occasionally patients are transferred from Non-Specialist Paediatric Surgical Centres (NSPSC) for specialised pre-operative or post-operative care., Aim: To assess the rates of and characterise appendicitis-related referrals to CHI at Crumlin from NSPSC., Methods: A retrospective review of all appendicitis-related transfers to CHI at Crumlin between January 2020 and December 2021 was performed. Data relating to indications for transfer, referring hospital level, patient demographics, management, type of surgery, length of stay (LOS), and radiological studies were collected and analysed., Results: Seventy-two patients were transferred to CHI at Crumlin over the 2-year period. A total of 60.9% were male, mean age 9 ± 4.3 years, mean LOS 6.0 ± 2.2 days (range 1-30 days). Nineteen percent were under 5 years of age. Seventy-three percent were transferred from level 4 centres. Ninety-seven percent were transferred pre-operatively, 25% of those transferred pre-operatively had imaging in CHI confirming appendicitis. Fifty-five percent (40/72) of patients had pre-operative imaging performed. A total of 37.5% (15/40) confirmed complicated appendicitis. Twenty percent (8/40) underwent both ultrasound and computerised tomography (CT) at the referring centre. A total of 2.7% (2/72) were transferred with known co-morbidities. Ninety-two percent (66/72) underwent appendicectomy. Eight percent (6/72) were managed non-operatively (NOM) - 2 failed NOM, 2 underwent interval appendicectomy. Of those managed operatively, 76% (50/66) underwent laparoscopic appendicectomy, and 24% (16/66) were performed open., Conclusion: The majority of paediatric appendicectomies are performed at Non-Specialist Paediatric Surgical Centres. It is vital to maintain this working relationship so that specialist paediatric centres are available to provide care to complex paediatric patients., (© 2023. The Author(s).)

Health care providers caring for patients at the end of life (EOL) are faced with a multitude of emotions such as guilt, anger, sadness, and helplessness. Because of the negative impact of initiating EOL care (EOLC) to the pediatric population, organizations must be proactive in instituting education and resources on EOLC. They must also provide advanced skills to nurses who take care of patients at their EOL. Understanding the consequences of providing EOL care to patients in the pediatric intensive care unit allows for better allocation of resources and support services for nurses. This improves patient outcomes and nurse retention., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Cork University Hospital acts as the tertiary referral centre for the HSE southern area, with a catchment population of 1.2 million [1]. The neurology registrars receive telephone consultations from hospitals and primary care practices in the region. While there have been a number of studies examining inpatient neurology consultations in Irish hospitals [2-6], there is a paucity of data examining the support provided by tertiary referral centres to other acute hospitals and primary care centres in their region., Aims: The aim of this study is to define the workload of the neurology registrar with respect to telephone consultations and to examine the quality of these referrals., Methods: All calls received from the 19th of October 2021 to the 25th of February 2022 were logged by the receiving registrar. Information collected pertained to the nature of the consult and completeness of the referral., Results: The average volume of calls during the study period was six per week. The median call duration was 8 min. The cumulative time spent resolving outside calls during the study period was at least 41.25 hours. Sixty-three per cent of calls were from other acute hospitals in the region. Thirty-nine per cent of referrals were deemed incomplete with respect to either history, collateral history or examination., Conclusions: This is a necessary service in a system that is not adequately resourced to provide specialist led care in all hospitals. A greater emphasis on complete and accurate referrals, along with robust communication and documentation, could reduce the inherent risk associated with such consultations., (© 2022. The Author(s), under exclusive licence to Royal Academy of Medicine in Ireland.)

Plasmodium parasites are the etiological agents of malaria, a disease responsible for over half a million deaths annually. Successful completion of the parasite's life cycle in the vertebrate host and transmission to a mosquito vector is contingent upon the ability of the parasite to evade the host's defenses. The extracellular stages of the parasite, including gametes and sporozoites, must evade complement attack in both the mammalian host and in the blood ingested by the mosquito vector. Here, we show that Plasmodium falciparum gametes and sporozoites acquire mammalian plasminogen and activate it into the serine protease plasmin to evade complement attack by degrading C3b. Complement-mediated permeabilization of gametes and sporozoites was higher in plasminogen-depleted plasma, suggesting that plasminogen is important for complement evasion. Plasmin also facilitates gamete exflagellation through complement evasion. Furthermore, supplementing serum with plasmin significantly increased parasite infectivity to mosquitoes and lowered the transmission-blocking activity of antibodies to Pfs230, a potent vaccine candidate currently in clinical trials. Finally, we show that human factor H, previously shown to facilitate complement evasion by gametes, also facilitates complement evasion by sporozoites. Plasmin and factor H simultaneously cooperate to enhance complement evasion by gametes and sporozoites. Taken together, our data show that Plasmodium falciparum gametes and sporozoites hijack the mammalian serine protease plasmin to evade complement attack by degrading C3b. Understanding of the mechanisms of complement evasion by the parasite is key to the development of novel effective therapeutics. IMPORTANCE Current approaches to control malaria are complicated by the development of antimalarial-resistant parasites and insecticide-resistant vectors. Vaccines that block transmission to mosquitoes and humans are a plausible alternative to overcome these setbacks. To inform the development of efficacious vaccines, it is imperative to understand how the parasite interacts with the host immune response. In this report, we show that the parasite can co-opt host plasmin, a mammalian fibrinolytic protein to evade host complement attack. Our results highlight a potential mechanism that may reduce efficacy of potent vaccine candidates. Taken together, our results will inform future studies in developing novel antimalarial therapeutics., Competing Interests: The authors declare no conflict of interest.

Objective: This systematic review evaluates all published studies comparing biologic and synthetic meshes in implant-based breast reconstruction (IBBR), to determine which category of mesh produces the most favorable outcomes., Summary Background Data: Breast cancer is the most common cancer in women globally. Implant-based breast reconstruction is currently the most popular method of postmastectomy reconstruction, and recently, the use of surgical mesh in IBBR has become commonplace. Although there is a long-standing belief among surgeons that biologic mesh is superior to synthetic mesh in terms of surgical complications and patient outcomes, few studies exist to support this claim., Methods: A systematic search of the EMBASE, PubMed, and Cochrane databases was performed in January 2022. Primary literature studies comparing biologic and synthetic meshes within the same experimental framework were included. Study quality and bias were assessed using the validated Methodological Index for Non-Randomized Studies criteria., Results: After duplicate removal, 109 publications were reviewed, with 12 meeting the predetermined inclusion criteria. Outcomes included common surgical complications, histological analysis, interactions with oncologic therapies, quality of life measures, and esthetic outcomes. Across all 12 studies, synthetic meshes were rated as at least equivalent to biologic meshes for every reported outcome. On average, the studies in this review tended to have moderate Methodological Index for Non-Randomized Studies scores., Conclusion: This systematic review offers the first comprehensive evaluation of all publications comparing biologic and synthetic meshes in IBBR. The consistent finding that synthetic meshes are at least equivalent to biologic meshes across a range of clinical outcomes offers a compelling argument in favor of prioritizing the use of synthetic meshes in IBBR., Competing Interests: Conflicts of interest and sources of funding: none declared., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: The purpose of this study was to gain knowledge of the educational preparation and attitudes of registered nurses at a southeastern pediatric hospital toward caring for dying children and their families., Design and Methods: A descriptive study with two independent samples was used to examine the attitudes of registered nurses at a pediatric hospital in southeastern United States. Participants completed the Frommelt Attitude Toward Care of the Dying Scale, Form B, a 30-item survey. Descriptive and inferential statistics were used to analyze data., Results: One hundred and thirty-two registered nurses participated in the study. Results indicated a statistically significant difference in attitudes toward caring for dying pediatric patient scores in registered nurses working in the hematology/oncology and intensive care units compared to the other units (p = 0.0017; 95% CI: 2.39-10.12)., Conclusions: This study described the educational preparation and attitudes of registered nurses who care for children who are dying and their families. Additionally, pediatric end-of-life care is complex and is further influenced by experiences and attitudes. Future research is needed to identify educational needs to care for pediatric patients and their families at the end of life., Practice Implications: Findings from this project indicated end-of-life care education should be integrated into undergraduate curricula. New nurse graduates who are entering the workforce should receive education on end-of-life care, especially if they are entering into a pediatric specific organization. Healthcare organizations should include end-of-life care education as part of the orientation process and annual competency process., Competing Interests: Declaration of Competing Interest The authors declare no competing interests., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Background: A woman's vulnerability to sleep disruption and mood disturbance is heightened during the perinatal period and there is a strong bidirectional relationship between them. Both sleep disruption and mood disturbance can result in significant adverse outcomes for women and their infant. Thus, supporting and improving sleep in the perinatal period is not only an important outcome in and of itself, but also a pathway through which future mental health outcomes may be altered., Methods: Using scoping review methodology, we investigated the nature, extent and characteristics of intervention studies conducted during the perinatal period (pregnancy to one-year post-birth) that reported on both maternal sleep and maternal mental health. Numerical and descriptive results are presented on the types of studies, settings, sample characteristics, intervention design (including timeframes, facilitation and delivery), sleep and mood measures and findings., Results: Thirty-seven perinatal interventions were identified and further described according to their primary focus (psychological (n = 9), educational (n = 15), lifestyle (n = 10), chronotherapeutic (n = 3)). Most studies were conducted in developed Western countries and published in the last 9 years. The majority of study samples were women with existing sleep or mental health problems, and participants were predominantly well-educated, not socio-economically disadvantaged, in stable relationships, primiparous and of White race/ethnicity. Interventions were generally delivered across a relatively short period of time, in either the second trimester of pregnancy or the early postnatal period and used the Pittsburgh Sleep Quality Index (PSQI) to measure sleep and the Edinburgh Postnatal Depression Scale (EPDS) to measure mood. Retention rates were high (mean 89%) and where reported, interventions were well accepted by women. Cognitive Behavioural Therapies (CBT) and educational interventions were largely delivered by trained personnel in person, whereas other interventions were often self-delivered after initial explanation., Conclusions: Future perinatal interventions should consider spanning the perinatal period and using a stepped-care model. Women may be better supported by providing access to a range of information, services and treatment specific to their needs and maternal stage. The development of these interventions must involve and consider the needs of women experiencing disadvantage who are predominantly affected by poor sleep health and poor mental health., (© 2022. The Author(s).)

In mammals, the serine protease plasmin degrades extracellular proteins during blood clot removal, tissue remodeling, and cell migration. The zymogen plasminogen is activated into plasmin by two serine proteases: tissue-type plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), a process regulated by plasminogen activator inhibitor 1 (PAI-1), a serine protease inhibitor that specifically inhibits tPA and uPA. Plasmodium gametes and sporozoites use tPA and uPA to activate plasminogen and parasite-bound plasmin degrades extracellular matrices, facilitating parasite motility in the mosquito and the mammalian host. Furthermore, inhibition of plasminogen activation by PAI-1 strongly blocks infection in both hosts. To block parasite utilization of plasmin, we engineered Anopheles stephensi transgenic mosquitoes constitutively secreting human PAI-1 (huPAI-1) in the midgut lumen, in the saliva, or both. Mosquitoes expressing huPAI-1 strongly reduced rodent and human Plasmodium parasite transmission to mosquitoes, showing that co-opting plasmin for mosquito infection is a conserved mechanism among Plasmodium species. huPAI-1 expression in saliva induced salivary gland deformation which affects sporozoite invasion and P. berghei transmission to mice, resulting in significant levels of protection from malaria. Targeting the interaction of malaria parasites with the fibrinolytic system using genetically engineered mosquitoes could be developed as an intervention to control malaria transmission., (© 2022. This is a U.S. government work and not under copyright protection in the U.S.; foreign copyright protection may apply.)

An accurate understanding of the changes in height and weight of children with age is critical to the development of models predicting drug concentrations in children (i.e., physiologically-based pharmacokinetic models). However, curves describing the growth of a typical population of children may not accurately characterize growth of children with various conditions, such as obesity. Therefore, to develop height and weight versus age growth curves for youth who were diagnosed with type 2 diabetes, we extracted data from electronic medical records. Robust nonlinear models were parameterized to the equations describing height and weight versus age as defined by the Centers for Disease Control and Prevention (CDC). CDC z-scores were calculated using an internal program. The growth curves and z-scores were compared to CDC norms. Youth with type 2 diabetes were increasingly heavier than CDC norms from early childhood. Except for a period around puberty, youth with type 2 diabetes were, on average, shorter than CDC norms, resulting in shorter average adult height. Deviations in growth were apparent in youth who develop type 2 diabetes; such deviations may be expected for other conditions as well, and disease-specific growth curves should be considered during development of model-informed drug development for pediatric conditions., (© 2022 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

Objective: To describe characteristics of paediatric weight management (PWM) programs across the United States and evaluate associations with program-specific retention rates and body mass index (BMI) outcomes at 6 months., Methods: A program profile survey was administered to 33 programs within the Paediatric Obesity Weight Evaluation Registry (POWER) to assess program staffing, services, and treatment format. Patient retention and percent of the 95th BMI percentile (%BMIp95) changes were assessed for each program., Results: At 6 months program retention rates ranged from 15% to 74% (median: 41%), and program %BMIp95 changes ranged from -9.0 to +0.5 percentage points (median: -1.7). Percent of patients with ≥5 percentage-point decrease in %BMIp95 ranged from 17% to 71% across programs (median: 29%). No associations were detected between program characteristics and retention or %BMIp95 changes., Conclusions: Six-month patient retention and BMI outcomes vary substantially in PWM programs across the United States. Yet, no associations were found between PWM treatment factors and these program-level patient outcomes., (© 2021 World Obesity Federation.)

Plasmodium and other vector-borne pathogens have evolved mechanisms to hijack the mammalian fibrinolytic system to facilitate infection of the human host and the invertebrate vector. Plasmin, the effector protease of fibrinolysis, maintains homeostasis in the blood vasculature by degrading the fibrin that forms blood clots. Plasmin also degrades proteins from extracellular matrices, the complement system, and immunoglobulins. Here, we review some of the mechanisms by which vector-borne pathogens interact with components of the fibrinolytic system and co-opt its functions to facilitate transmission and infection in the host and the vector. Further, we discuss innovative strategies beyond conventional therapeutics that could be developed to target the interaction of vector-borne pathogens with the fibrinolytic proteins and prevent their transmission., Competing Interests: Declaration of interests The authors declare no competing interests., (Published by Elsevier Ltd.)

Acquired vocal cord paralysis (VCP) is caused by dysfunction or injury of one or both recurrent laryngeal nerves. Here we report a 41-year-old man with spinocerebellar atrophy, autosomal recessive type 10 (SCAR10) due to an autosomal recessive mutation in the ANO10 gene, with VCP as the presenting symptom. He later developed ataxia and speech disturbance., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

A 23- year-man post female to male (FTM) gender transition was found to have bilateral papilloedema at a routine optician visit. The patient was referred on for formal ophthalmological and neurological assessments. Optical coherence tomography (OCT) confirmed the presence of bilateral papilloedema. The patient was entirely asymptomatic and had no medical history. He took testosterone intramuscularly once per month. Neurological examination was otherwise normal. Investigations including routine blood panels, CT brain, MRI brain and cerebral MR venogram were all normal. Lumbar puncture yielded cerebrospinal fluid (CSF) normal in appearance but demonstrated raised intracranial pressure. In the absence of other causative aetiologies a diagnosis of idiopathic intracranial hypertension (IIH) was made. Treatment was commenced with acetazolamide and the patient was discharged with outpatient ophthalmological and neurological follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Monoclonal antibodies are the leading class of biopharmaceuticals in terms of numbers approved for therapeutic purposes. Antigen-binding fragments (Fab) are also used as biotherapeutics and used widely in research applications. The dominant expression systems for full-length antibodies are mammalian cell-based, whereas for Fab molecules the preference has been an expression in bacterial systems. However, advances in CHO and downstream technologies make mammalian systems an equally viable option for small- and large-scale Fab production. Using a panel of full-length IgG antibodies and their corresponding Fab pair with different antigen specificities, we investigated the impact of the IgG and Fab molecule format on production from Chinese hamster ovary (CHO) cells and assessed the cellular capability to process and produce these formats. The full-length antibody format resulted in the recovery of fewer mini-pools posttransfection when compared to the corresponding Fab fragment format that could be interpreted as indicative of a greater overall burden on cells. Antibody-producing cell pools that did recover were subsequently able to achieve higher volumetric protein yields (mg/L) and specific productivity than the corresponding Fab pools. Importantly, when the actual molecules produced per cell of a given format was considered (as opposed to mass), CHO cells produced a greater number of Fab molecules per cell than obtained with the corresponding IgG, suggesting that cells were more efficient at making the smaller Fab molecule. Analysis of cell pools showed that gene copy number was not correlated to the subsequent protein production. The amount of mRNA correlated with secreted Fab production but not IgG, whereby posttranscriptional processes act to limit antibody production. In summary, we provide the first comparative description of how full-length IgG and Fab antibody formats impact on the outcomes of a cell line construction process and identify potential limitations in their production that could be targeted for engineering increases in the efficiency in the manufacture of these recombinant antibody formats., (© 2021 The Authors. Biotechnology and Bioengineering published by Wiley Periodicals LLC.)

A rapid analytical method for quantifying 90 Sr in infant formula prior to secular equilibrium is presented. The approach is dependent on the use of two separations of 90 Sr from 90 Y, with the first providing an 90 Y ingrowth start point and the second providing an 90 Y ingrowth end point. Data were obtained at activity concentrations of approximately 6 Bq/kg and 160 Bq/kg, the latter of which is representative of the US Food and Drug Administration (FDA) Derived Intervention Levels (DIL). Experiments were designed to collect data from ingrowth periods ranging from 16 h to 2 weeks. Activities obtained with a separation interval as low as 16 h ranged from 92.7 to 109.4% of the known value. When 90 Y ingrowth was allowed to occur for 24 h or longer, the activities ranged from 93.2 to 106.2% of the known value and the precision of this group improved from 5.2 to 3.1%. The limit of quantification (LOQ) was 0.5 Bq/kg using 250 g sample portions.