Mutational landscape of risk variants in comorbid depression and obesity: a next-generation sequencing approach.

Major depression (MD) and obesity are complex genetic disorders that are frequently comorbid. However, the study of both diseases concurrently remains poorly addressed and therefore the underlying genetic mechanisms involved in this comorbidity remain largely unknown. Here we examine the contribution of common and rare variants to this comorbidity through a next-generation sequencing (NGS) approach. Specific genomic regions of interest in MD and obesity were sequenced in a group of 654 individuals from the PISMA-ep epidemiological study. We obtained variants across the entire frequency spectrum and assessed their association with comorbid MD and obesity, both at variant and gene levels. We identified 55 independent common variants and a burden of rare variants in 4 genes (PARK2, FGF21, HIST1H3D and RSRC1) associated with the comorbid phenotype. Follow-up analyses revealed significantly enriched gene-sets associated with biological processes and pathways involved in metabolic dysregulation, hormone signaling and cell cycle regulation. Our results suggest that, while risk variants specific to the comorbid phenotype have been identified, the genes functionally impacted by the risk variants share cell biological processes and signaling pathways with MD and obesity phenotypes separately. To the best of our knowledge, this is the first study involving a targeted sequencing approach toward the study of the comorbid MD and obesity. The framework presented here allowed a deep characterization of the genetics of the co-occurring MD and obesity, revealing insights into the mutational and functional profile that underlies this comorbidity and contributing to a better understanding of the relationship between these two disabling disorders.

Clinical and Molecular Profiling in GNAO1 Permits Phenotype-Genotype Correlation.

BACKGROUND: Defects in GNAO1, the gene encoding the major neuronal G-protein Gαo, are related to neurodevelopmental disorders, epilepsy, and movement disorders. Nevertheless, there is a poor understanding of how molecular mechanisms explain the different phenotypes. OBJECTIVES: We aimed to analyze the clinical phenotype and the molecular characterization of GNAO1-related disorders. METHODS: Patients were recruited in collaboration with the Spanish GNAO1 Association. For patient phenotyping, direct clinical evaluation, analysis of homemade-videos, and an online questionnaire completed by families were analyzed. We studied Gαo cellular expression, the interactions of the partner proteins, and binding to guanosine triphosphate (GTP) and G-protein-coupled receptors (GPCRs). RESULTS: Eighteen patients with GNAO1 genetic defects had a complex neurodevelopmental disorder, epilepsy, central hypotonia, and movement disorders. Eleven patients showed neurological deterioration, recurrent hyperkinetic crisis with partial recovery, and secondary complications leading to death in three cases. Deep brain stimulation improved hyperkinetic crisis, but had inconsistent benefits in dystonia. The molecular defects caused by pathogenic Gαo were aberrant GTP binding and hydrolysis activities, an inability to interact with cellular binding partners, and reduced coupling to GPCRs. Decreased localization of Gαo in the plasma membrane was correlated with the phenotype of "developmental and epileptic encephalopathy 17." We observed a genotype-phenotype correlation, pathogenic variants in position 203 were related to developmental and epileptic encephalopathy, whereas those in position 209 were related to neurodevelopmental disorder with involuntary movements. Milder phenotypes were associated with other molecular defects such as del.16q12.2q21 and I344del. CONCLUSION: We highlight the complexity of the motor phenotype, which is characterized by fluctuations throughout the day, and hyperkinetic crisis with a distinct post-hyperkinetic crisis state. We confirm a molecular-based genotype-phenotype correlation for specific variants. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Transarterial Embolization for Adhesive Capsulitis of the Shoulder: Midterm Outcomes on Function and Pain Relief.

PURPOSE: To determine the safety and potential effectiveness of transarterial embolization for adhesive capsulitis of the shoulder. MATERIALS AND METHODS: This prospective study analyzed consecutive adult patients with adhesive capsulitis referred for embolization between January 2018 and May 2023 after a poor response to treatment (symptoms and limitation of motion in ≥2 axes; ≤120° flexion, ≤50° external rotation and/or internal rotation with the shoulder abducted 90°) persisting for >3 months after having completed ≥6 weeks of analgesics and physical therapy. Different types of pain and mobility were measured before embolization and 1, 3, and 6 months after embolization. Overall upper limb function (Quick Disabilities of Arm, Shoulder, and Hand) and patient satisfaction were measured before and 6 months after embolization. Long-term follow-up comprised telephone interviews and clinical history reviews. RESULTS: A total of 20 patients (12 [60%] women; median age, 50.7; interquartile ranges [IQR], 45‒55 years) were included; 6 (30%) had diabetes and 15 (75%) were off work. Median duration of symptoms before embolization was 39.4 weeks (IQR, 28‒49 weeks), and median duration of rehabilitation therapy was 12.8 weeks (IQR, 8‒16 weeks). Six months after embolization, significant improvements were observed in nocturnal pain (P = .003), pain on moving (P = .001), external rotation (P < .001), internal rotation (P < .001), active flexion (P < .001), passive flexion (P = .03), active abduction (P < .001), passive abduction (P < .001), and overall function (P < .001). Despite objective improvements, patient satisfaction was nearly unchanged. Only 1 patient experienced a mild adverse event. CONCLUSION: Transarterial embolization is safe and potentially effective in treating adhesive capsulitis of the shoulder refractory to conventional treatment. Clinical improvements were maintained in the mid to long term.

Evaluation of Genetic Variants Associated with the Risk of Thiopurine-Related Pancreatitis: A Case Control Study from ENEIDA Registry.

INTRODUCTION: Risk factors for developing pancreatitis due to thiopurines in patients with inflammatory bowel disease (IBD) are not clearly identified. Our aim was to evaluate the predictive pharmacogenetic risk of pancreatitis in IBD patients treated with thiopurines. METHODS: We conducted an observational pharmacogenetic study of acute pancreatitis events in a cohort study of IBD patients treated with thiopurines from the prospectively maintained ENEIDA registry biobank of GETECCU. Samples were obtained and the CASR, CEL, CFTR, CDLN2, CTRC, SPINK1, CPA1, and PRSS1 genes, selected based on their known association with pancreatitis, were fully sequenced. RESULTS: Ninety-five cases and 105 controls were enrolled; a total of 57% were women. Median age at pancreatitis diagnosis was 39 years. We identified 81 benign variants (50 in cases and 67 in controls) and a total of 35 distinct rare pathogenic and unknown significance variants (10 in CEL, 21 in CFTR, 1 in CDLN2, and 3 in CPA1). None of the cases or controls carried pancreatitis-predisposing variants within the CASR, CPA1, PRSS1, and SPINK1 genes, nor a pathogenic CFTR mutation. Four different variants of unknown significance were detected in the CDLN and CPA1 genes; one of them was in the CDLN gene in a single patient with pancreatitis and 3 in the CPA1 gene in 5 controls. After the analysis of the variants detected, no significant differences were observed between cases and controls. CONCLUSION: In patients with IBD, genes known to cause pancreatitis seem not to be involved in thiopurine-related pancreatitis onset.

Bridging the gap: Experimental evidence on information provision and health insurance choices.

Previous research has shown that individuals do not always make rational decisions when selecting their health insurance, for example, due to the existence of information frictions or mental gaps. We study the effect of specific types of information provision for decision support on health plan choices and test their potential to improve decision quality by implementing a randomized laboratory experiment. We provide personalized and generic aids, differentiate between numerical and visual decision support, and provide one or two optional formats of personalized information. We find that generic aids have no effect on health plan choices while personalized information leads to better choices as measured by several indicators of decision quality. The largest effects were observed for those who "opted in" to visualize personalized information, with immediate and lasting improvements in health insurance decisions. By reducing information frictions, our results suggest that accessible and easy-to-use tools can positively impact health insurance navigation, improve decision-making, and reduce switching costs.

Equity, diversity, and inclusion in the Multinational Association for Supportive Care in Cancer: a global membership survey.

Equity, diversity, and inclusion (EDI) are essential for healthcare organizations since they allow for the development of programs and initiatives that bring together diverse perspectives and knowledge. Global multidisciplinary organizations, such as the Multinational Association for Supportive Care in Cancer (MASCC), need to understand the perspective of their members regarding EDI to identify opportunities to enhance diversity and inclusiveness and to better meet the needs of members from different backgrounds and resources. The MASCC Health Disparities Committee designed a survey to identify issues related to disparities faced by MASCC members when providing supportive care to patients with cancer and to examine the EDI landscape within the organization. Here, we report results related to EDI initiatives within the organization. Two-hundred and eighteen MASCC members responded to the survey (response rate 10.2%). The results indicated that respondents were generally satisfied with how MASCC manages leadership, membership, and organization-related EDI issues. Opportunities for improvement noted by respondents included developing strategies to foster a more diverse membership, improving communication regarding diversity in the organization, and increasing EDI content in educational sessions and publications. The results of this survey represent the first attempt at understanding how to improve EDI within MASCC and will be utilized to guide further initiatives and programs.

Influence of different midsole foam in advanced footwear technology use on running economy and biomechanics in trained runners.

BACKGROUND: Ethylene and vinyl acetate (EVA) and polyether block amide (PEBA) are recently the most widely used materials for advanced footwear technology (AFT) that has been shown to improve running economy (RE). This study investigated the effects of these midsole materials on RE and biomechanics, in both fresh and worn state (after 450 km). METHODS: Twenty-two male trained runners participated in this study. Subjects ran four 4-min trials at 13 km‧h-1 with both fresh EVA and PEBA AFT and with the same models with 450 km of wear using a randomized crossover experimental design. We measured energy cost of running (W/kg), spatiotemporal, and neuromuscular parameters. RESULTS: There were significant differences in RE between conditions (p = 0.01; n2 = 0.17). There was a significant increase in energy cost in the worn PEBA condition compared with new (15.21 ± 1.01 and 14.87 ± 0.99 W/kg; p < 0.05; ES = 0.54), without differences between worn EVA (15.13 ± 1.14 W/kg; p > 0.05), and new EVA (15.15 ± 1.13 w/kg; ES = 0.02). The increase in energy cost between new and worn was significantly higher for the PEBA shoes (0.32 ± 0.38 W/kg) but without significant increase for the EVA shoes (0.06 ± 0.58 W/kg) (p < 0.01; ES = 0.51) with changes in step frequency and step length. The new PEBA shoes had lower energy cost than the new EVA shoes (p < 0.05; ES = 0.27) with significant differences between conditions in contact time. CONCLUSION: There is a clear RE advantage of incorporating PEBA versus EVA in an AFT when the models are new. However, after 450 km of use, the PEBA and EVA shoes had similar RE.

Barbed versus conventional suture in elective posterior spine surgery.

PURPOSE: Barbed sutures are tissue control devices that can reduce operating room time and costs. We analyzed the utility of barbed sutures in posterior spinal surgery in order to prove non-inferiority to conventional methods for wound closure. METHODS: A cohort of patients undergoing elective posterior spinal surgery in which barbed (prospective) versus conventional sutures (retrospective) were used was analyzed. The primary endpoint was the occurrence of wound healing complications or the need for surgical revision. Secondary endpoints included postoperative stay, readmission rate, and duration and cost of wound closure. RESULT: A total of 483 patients participated in the study, 183 in the Barbed group and 300 in the Conventional group. Wound dehiscence or seroma occurred in 3.8% and 2.7% of the Barbed and Conventional groups, respectively (p = 0.6588). Both superficial (1.6% versus 4.0%, P = 0.2378) and deep infections (2.7% versus 4.7%, p = 0.4124) occurred similarly in both groups. Overall, the rate of re-intervention due to wound healing problems was also similar (4.9% versus 5.3%, p = 0.9906), as well as, total median hospital stay, postoperative stay and 30-day re-admission rates. The average duration of wound closure (1.66 versus 4.16 min per level operated, p < 0.0001) strongly favored the Barbed group. The mean cost of wound closure per patient was higher in the Barbed group (43.23 € versus 22.67 €, p < 0.0001). CONCLUSIONS: In elective posterior spinal procedures, the use of barbed sutures significantly reduced the duration of wound closure. The wound healing process was not hindered and the added cost related to the suture material was small.

Content Validity of the Spanish Adaptation of the Premature Infant Pain Profile Revised.

BACKGROUND: To the best of our knowledge, there are no validated neonatal pain assessment scales in Spanish. Given the need for such a scale, a study was undertaken to adapt and validate the Premature Infant Pain Profile-Revised (PIPP-R) scale. After translation and back-translation, content validity was addressed, a crucial phase in validation studies, in which researchers examine whether the items that make up the scale represent the content that the scale is intended to assess. AIMS: The aim was to provide evidence for the content validity of the Spanish adaptation of the PIPP-R scale. METHOD: The study used the Delphi technique with 10 experts. Data collection was anonymous and was conducted through an online platform. It was an ad hoc survey consisting of four questions, with a five-point Likert scale for each item on the scale and for the instruction table. An item-content validity index (I-CVI) and a scale-content validity index (S-CVI) were calculated for the analysis. RESULTS: After two rounds of the survey, all items exceeded an I-CVI of 0.9. The S-CVI value was 0.98 (±0.03) for the scale, and 1 for its instruction table. The kappa index yielded values indicating an excellent degree of agreement. CONCLUSIONS: The Spanish version of the PIPP-R obtained a high degree of content validity according to the expert group and the Delphi technique.

Recommendations on the management of severe obesity in patients with inflammatory bowel disease of the Spanish Group on Crohn's Disease and Ulcerative Colitis (GETECCU), Spanish Society of Obesity (SEEDO), Spanish Association of Surgery (AEC) and Spanish Society of Digestive Endoscopy (SEED). / Recomendaciones sobre el manejo de la obesidad grave en pacientes con enfermedad inflamatoria intestinal del Grupo Español de Trabajo en Enfermedad Inflamatoria Intestinal (GETECCU), Sociedad Española de Obesidad (SEEDO), Asociación Española de Cirugía (AEC) y Sociedad Española de Endoscopia Digestiva (SEED).

Obesity is a multifactorial, chronic, progressive and recurrent disease considered a public health issue worldwide and an important determinant of disability and death. In Spain, its current prevalence in the adult population is about 24% and an estimated prevalence in 2035 of 37%. Obesity increases the probability of several diseases linked to higher mortality such as diabetes, cardiovascular disease, hyperlipidemia, arterial hypertension, non-alcoholic fatty liver disease, several types of cancer, or obstructive sleep apnea. On the other hand, although the incidence of inflammatory bowel disease (IBD) is stabilizing in Western countries, its prevalence already exceeds 0.3%. Paralleling to general population, the current prevalence of obesity in adult patients with IBD is estimated at 15-40%. Obesity in patients with IBD could entail, in addition to its already known impact on disability and mortality, a worse evolution of the IBD itself and a worse response to treatments. The aim of this document, performed in collaboration by four scientific societies involved in the clinical care of severe obesity and IBD, is to establish clear and concise recommendations on the therapeutic possibilities of severe or typeIII obesity in patients with IBD. The document establishes general recommendations on dietary, pharmacological, endoscopic, and surgical treatment of severe obesity in patients with IBD, as well as pre- and post-treatment evaluation.

Lateral kangaroo position for thermal stability of extremely preterm: Non-inferiority randomized controlled trial.

BACKGROUND: Kangaroo care (KC) is an evidence-based best practice that can prevent major health complications in preterm infants. However, there is a lack of evidence on the feasibility and safety of placing extremely preterm infants under 28 weeks gestational age in KC position. AIM: To compare thermal stability 60 min after the first KC session in the lateral versus prone position in extremely preterm infants under 28 weeks gestational age. STUDY DESIGN: This is a single-centre, randomized, non-inferiority, parallel clinical trial. The patients were extremely preterm infants during their first 5 days of life. Infants in the intervention group received KC in the lateral position while those in the control group received KC in the prone position. All infants receiving KC were inside their polyethylene bags but maintained skin-to-skin contact. The primary outcome was the axillary temperature of the infants, and the secondary outcome was the development of intraventricular haemorrhage. RESULTS: Seventy infants were randomized (35 per group). The mean gestational age was 26 +1(1+1) in both groups. In the first KC session, the infant temperature at 60 minutes was 36.79°C (0.43) in lateral KC position, and 36.78°C (0.38) in prone KC position (p = .022). In lateral KC position, 7.69% (2) of the children who, according to the cranial ultrasound performed before the first session, had no haemorrhage presented with intraventricular haemorrhage after the first session. In prone KC position, new haemorrhages appeared after the first session in 29.17% (7) (p = .08). CONCLUSIONS: The lateral KC position is an alternative to the conventional prone KC position and maintains normothermia in infants under 28 weeks gestational age. RELEVANCE TO CLINICAL PRACTICE: Extremely preterm infants are candidates for KC. Lateral KC position is an evidence-based best practice that can be applied to preterm infants under 28 weeks GA. This evidence is particularly useful in performing umbilical catheterization on these patients.

Latent classes of gambling in youths: The role of comorbidity, alexithymia and stressful life events by sex. / Clases latentes de juego problemático en jóvenes: El papel de la comorbilidad, la alexitimia y los acontecimientos vitales estresantes en función del sexo.

Alexithymia is related with propensity towards impulsive behavioral responses, rather than cognitive regulation of stressful events. Youth is a particularly vulnerable time for the confluence of these variables, which may impact the severity of gambling disorders (GD). However, sex differences have hardly been explored. This study aimed, firstly, to explore the frequency of GD among young people, as well as the presence of GD with other comorbid addictions. Secondly, latent classes were examined on the basis of gambling risk and their relationship to other addictive behaviors, alexithymia and stressful life events. Thirdly, we analyzed whether class membership was predicted by sex and age. The sample was composed of 360 participants between the ages of 18 and 35, the majority female. The results obtained revealed that alcohol abuse was the most prevalent addictive behavior both for problem and non-problem gamblers of both sexes. Group membership analyses showed the presence of two latent classes based on gambling risk. One of them was characterized by gambling risk, comorbidity, alexithymia, and stressful life events, and mainly predicted by being male. The other model was characterized by no gambling risk, lower levels of stressful life events and alexithymia, and mainly predicted by being female. This second profile presents a risk of alcohol abuse and compulsive buying. We highlight the need to introduce a gender perspective both in the interpretation of research findings and in the clinical application of treatments. CAST: La comorbilidad, la alexitimia y los acontecimientos vitales estresantes desempeñan un papel importante en la salud mental de los jóvenes. Este estudio ha tenido como objetivo, en primer lugar, explorar la frecuencia del trastorno de juego (TJ) en los jóvenes, así como la presencia del TJ  con otras adicciones comórbidas. En segundo lugar, se pretendía analizar un modelo de perfil basado en el riesgo de juego y su relación con las otras conductas adictivas, la alexitimia y los acontecimientos vitales estresantes. En tercer lugar, se analizó si la pertenencia a cada perfil era predicha por el sexo y la edad. La muestra estaba compuesta por 360 participantes. Los resultados obtenidos revelaron que el abuso de alcohol era la conducta adictiva más prevalente tanto para los jugadores problemáticos como para los no problemáticos de ambos sexos. Los análisis de pertenencia de clase mostraron la presencia de dos modelos de perfil de juego. El primeor de ellos se caracterizaba por el riesgo de juego, la comorbilidad, la alexitimia y los acontecimientos vitales estresantes, y estaba principalmente predicho por la condición sexo-varón. El otro modelo se caracteriza por la ausencia de riesgo de juego, niveles más bajos de acontecimientos vitales estresantes y alexitimia, y se predice principalmente por ser mujer.  En este segundo perfil hay riesgo de abuso de alcohol y de compra compulsiva. Destacamos la necesidad de introducir una perspectiva de género tanto en la interpretación de los resultados de la investigación como en la aplicación clínica de los tratamientos.

La alexitimia se relaciona con la propensión a las respuestas conductuales impulsivas, en lugar de una regulación cognitiva de los acontecimientos estresantes. La juventud es una etapa de especial vulnerabilidad para la confluencia de estas variables, pudiendo repercutir en la severidad del trastorno de juego (TJ). No obstante, las diferencias entre sexos apenas han sido exploradas. Este estudio tuvo como objetivo, en primer lugar, explorar la frecuencia de TJ en los jóvenes, así como la presencia de TJ con otras adicciones comórbidas. En segundo lugar, se examinó el riesgo de juego y su relación con las otras conductas adictivas, la alexitimia y los acontecimientos vitales estresantes. En tercer lugar, se analizó si la pertenencia a una determinada clase latente era predicha por el sexo y la edad. La muestra estaba compuesta por 360 participantes, con edades comprendidas entre los 18 y 35 años, siendo la mayoría mujeres. Los resultados obtenidos revelaron que el abuso de alcohol era la conducta adictiva más prevalente, tanto para los jugadores problemáticos como para los no problemáticos de ambos sexos. Los análisis de pertenencia de grupo mostraron la presencia de dos clases latentes en base al riesgo de juego. El primero de ellos se caracterizaba por el riesgo de juego, la comorbilidad, la alexitimia y los acontecimientos vitales estresantes, y estaba principalmente predicho por la condición sexo-varón. El otro modelo se caracterizaba por la ausencia de riesgo de juego, niveles más bajos de acontecimientos vitales estresantes y alexitimia, y se predice principalmente por la condición sexo-mujer. En este segundo perfil se halló riesgo de abuso de alcohol y de compra compulsiva. Señalamos la necesidad de introducir una perspectiva de género tanto en la interpretación de los resultados de la investigación como en la aplicación clínica de los tratamientos.

Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Real-World Evidence of Tofacinitib in Ulcerative Colitis: Short-Term and Long-Term Effectiveness and Safety.

INTRODUCTION: The objective of this study was to assess the durability, short-term and long-term effectiveness, and safety of tofacitinib in ulcerative colitis (UC) in clinical practice. METHODS: This is a retrospective multicenter study including patients with UC who had received the first tofacitinib dose at least 8 weeks before the inclusion. Clinical effectiveness was based on partial Mayo score. RESULTS: A total of 408 patients were included. Of them, 184 (45%) withdrew tofacitinib during follow-up (mean = 18 months). The probability of maintaining tofacitinib was 67% at 6 m, 58% at 12 m, and 49% at 24 m. The main reason for tofacitinib withdrawal was primary nonresponse (44%). Older age at the start of tofacitinib and a higher severity of clinical activity were associated with tofacitinib withdrawal. The proportion of patients in remission was 38% at week 4, 45% at week 8, and 47% at week 16. Having moderate-to-severe vs mild disease activity at baseline and older age at tofacitinib start were associated with a lower and higher likelihood of remission at week 8, respectively. Of 171 patients in remission at week 8, 83 (49%) relapsed. The probability of maintaining response was 66% at 6 m and 54% at 12 m. There were 93 adverse events related to tofacitinib treatment (including 2 pulmonary thromboembolisms [in patients with risk factors] and 2 peripheral vascular thrombosis), and 29 led to tofacitinib discontinuation. DISCUSSION: Tofacitinib is effective in both short-term and long-term in patients with UC. The safety profile is similar to that previously reported.

Sensing of transposable elements by the antiviral innate immune system.

Around half of the genome in mammals is composed of transposable elements (TEs) such as DNA transposons and retrotransposons. Several mechanisms have evolved to prevent their activity and the detrimental impact of their insertional mutagenesis. Despite these potentially negative effects, TEs are essential drivers of evolution, and in certain settings, beneficial to their hosts. For instance, TEs have rewired the antiviral gene regulatory network and are required for early embryonic development. However, due to structural similarities between TE-derived and viral nucleic acids, cells can misidentify TEs as invading viruses and trigger the major antiviral innate immune pathway, the type I interferon (IFN) response. This review will focus on the different settings in which the role of TE-mediated IFN activation has been documented, including cancer and senescence. Importantly, TEs may also play a causative role in the development of complex autoimmune diseases characterised by constitutive type I IFN activation. All these observations suggest the presence of strong but opposing forces driving the coevolution of TEs and antiviral defence. A better biological understanding of the TE replicative cycle as well as of the antiviral nucleic acid sensing mechanisms will provide insights into how these two biological processes interact and will help to design better strategies to treat human diseases characterised by aberrant TE expression and/or type I IFN activation.

Flavonoids naringenin chalcone, naringenin, dihydrotricin, and tricin are lignin monomers in papyrus.

Recent studies demonstrate that several polyphenolic compounds produced from beyond the canonical monolignol biosynthetic pathways can behave as lignin monomers, participating in radical coupling reactions and being incorporated into lignin polymers. Here, we show various classes of flavonoids, the chalconoid naringenin chalcone, the flavanones naringenin and dihydrotricin, and the flavone tricin, incorporated into the lignin polymer of papyrus (Cyperus papyrus L.) rind. These flavonoids were released from the rind lignin by Derivatization Followed by Reductive Cleavage (DFRC), a chemical degradative method that cleaves the ß-ether linkages, indicating that at least a fraction of each was integrated into the lignin as ß-ether-linked structures. Due to the particular structure of tricin and dihydrotricin, whose C-3' and C-5' positions at their B-rings are occupied by methoxy groups, these compounds can only be incorporated into the lignin through 4'-O-ß bonds. However, naringenin chalcone and naringenin have no substituents at these positions and can therefore form additional carbon-carbon linkages, including 3'- or 5'-ß linkages that form phenylcoumaran structures not susceptible to cleavage by DFRC. Furthermore, Nuclear Magnetic Resonance analysis indicated that naringenin chalcone can also form additional linkages through its conjugated double bond. The discovery expands the range of flavonoids incorporated into natural lignins, further broadens the traditional definition of lignin, and enhances the premise that any phenolic compound present at the cell wall during lignification could be oxidized and potentially integrated into the lignin structure, depending only on its chemical compatibility. This study indicates that papyrus lignin has a unique structure, as it is the only lignin known to date that integrates such a diversity of phenolic compounds from different classes of flavonoids. This discovery will open up new ways to engineer and design lignins with specific properties and for enhanced value.

Vascular closure devices in living-donor nephrectomy: a much-needed systematic review and meta-analysis focusing on safety.

OBJECTIVE: To assess the safety of vascular closure devices in living-donor nephrectomy (LDN), as staplers and non-transfixion techniques (polymer locking and metal clips) are the methods employed to secure the renal vessels during laparoscopic and robotic LDN, but the use of clips has come into question since the United States Food and Drug Administration and manufacturers issued a contraindication. METHODS: A systematic review and meta-analysis were conducted to assess the safety of vascular closure devices (International Prospective Register of Systematic Reviews [PROSPERO] registration: CRD42022364349). The PubMed, Scopus, the Excerpta Medica dataBASE (EMBASE), and the Literatura Latino-Americana e do Caribe em Ciências da Saúde (LILACS) databases were searched in September 2022. For comparative and non-comparative studies, incidence estimates and odds ratios (ORs), respectively, for the main variables regarding safety of vascular closure devices were pooled by using random effects meta-analyses. Quality assessment of the included comparative studies was conducted using the Risk Of Bias In Non-randomised Studies of Interventions (ROBINS-I) tool. RESULTS: Of the 863 articles obtained, data were retrieved from 44 studies, which included 42 902 patients. In non-comparative studies, the pooled estimate rates for device failure, severe haemorrhage rate, conversion to open surgery, and mortality were similar for both clips and staplers. Regarding the meta-analyses for comparative studies (three studies), there were no significant differences between the two groups for the severe haemorrhage rate (OR 0.57, 95% confidence interval [CI] 0.18-1.75; P = 0.33), conversion to open surgery (OR 0.35, 95% CI 0.08-1.54; P = 0.16), or death rate (OR 3.64, 95% CI 0.47-28.45; P = 0.22). Based on weak evidence, device failure was lower in the polymer clip group (OR 0.41, 95% CI 0.23-0.75; P = 0.00). CONCLUSIONS: This study has confirmed that there is no evidence for the superiority of any vascular closure device in terms of safety in LDN. Standardised recommendations for vascular control in this context should be carefully designed and prospectively evaluated.

Early recognition of SGCE-myoclonus-dystonia in children.

AIM: To evaluate early dystonic features in children and adolescents with SGCE-myoclonus-dystonia. METHOD: In this cross-sectional study, 49 patients (26 females and 23 males) with SGCE-myoclonus-dystonia (aged 15y 2mo, SD 12y) with childhood-onset (2y 10mo, SD 1y 10mo) dystonia were examined using a standardized video recorded protocol. Dystonia was rated using the Writer's Cramp and Gait Dystonia Rating Scales. Disability and impairment for handwriting and walking were also rated. RESULTS: Dystonia was present at rest (n=1), posture (n=12), and during specific motor tasks (n=45) such as writing (n=35), walking (n=23), and running (n=20). Most children reported disability while performing these tasks. Early dystonic patterns were identified for writer's cramp and gait dystonia, the latter named the 'circular shaking leg', 'dragging leg', and 'hobby-horse gait' patterns. Sensory tricks were used by five and eight children to improve dystonia and myoclonus during writing and walking respectively. The rating scales accurately measured the severity of action dystonia and correlated with self-reported disability. INTERPRETATION: Children with SGCE-myoclonus-dystonia show recognizable dystonic patterns and sensory tricks that may lead to an early diagnosis and timely therapeutic approach. Isolated writer's cramp is a key feature in childhood and should prompt SCGE analysis. The proposed action dystonia scales could be used to monitor disease course and response to treatment. WHAT THIS PAPER ADDS: Most children with SGCE-myoclonus-dystonia got writer's cramp and had walking and running dystonia. Writer's cramp was a key feature and should prompt SGCE genetic investigation. 'Circular shaking leg', 'dragging leg', and 'hobby-horse gait' were recognized as early gait patterns. Children used sensory tricks to improve myoclonus and dystonia, suggesting common pathophysiological mechanisms. Action dystonia rating scales are valid tools to assess severity in children.

Association between biomarkers of iron status and cardiometabolic risk in Spanish children aged 9-10 years. The ELOIN study.

The relationship between iron metabolism and cardiometabolic risk factors has been scarcely studied in children, and the results are controversial. The objective of this study was to evaluate the association between iron parameters and lipid, glycemic and blood pressure alterations in the pediatric population. This was a cross-sectional study of 1954 children between 9 and 10 years of age in Madrid (Spain), participants in a longitudinal study of childhood obesity. Iron metabolism parameters, i.e., serum iron (Is), ferritin (Fs), transferrin (Tf) and transferrin saturation (STf) and lipid, glycemic and blood pressure profiles were evaluated. Odds ratios (ORs) were estimated using logistic regression models adjusted for sociodemographic characteristics, diet, physical activity, C-reactive protein and body mass index. Compared with the participants in the low Is and STf tertiles, those in the upper tertiles had a lower risk of low HDL-Chol (OR: 0.34; 95%CI: 0.17; 0.67) and OR: 0.44 (95%CI: 0.23; 0.84), respectively, and children in the upper Fs tertile had an OR of 2.07 (95%CI: 1.16; 3.68) for low HDL-Chol. Children in the highest Is and STf tertiles had a lower risk of prediabetes [OR: 0.63 (95%CI: 0.41; 0.97) and OR: 0.53 (95%CI: 0.34; 0.82)] and insulin resistance (IR) (OR: 0.37; 95%CI: 0.22; 0.64), and those in the upper Tf tertile had a higher risk of IR (OR: 1.90; 95%CI: 1.16; 3.12). An increased risk of hypertension was found only in children in the upper Fs tertile (OR: 1.46; 95%CI: 1.01; 2.13). CONCLUSIONS: Biomarkers of iron metabolism are associated with cardiometabolic alterations in the pediatric population, with a variable direction and magnitude depending on the indicators used. WHAT IS KNOWN: • Iron metabolism is related to important cardiometabolic alterations such as metabolic syndrome and its components. • Association between biomarkers of iron status and cardiometabolic risk have been less explored in children. WHAT IS NEW: • Biomarkers of iron metabolism are associated with cardiometabolic alterations in the pediatric population. • Iron parameters in the pediatric population could be of great help to detect and prevent cardiometabolic abnormalities early.

Nurse prescribing practices across the globe for medication-assisted treatment of the opioid use disorder (MOUD): a scoping review.

BACKGROUND: Despite the dramatic increase in opioid-related deaths in recent years, global access to treatment remains poor. A major barrier to people accessing Medication-assisted treatment of the opioid use disorder (MOUD) is the lack of providers who can prescribe and monitor MOUD. According to the World Drug Report, more young people are using drugs compared with previous generations and people in need of treatment cannot get it, women most of all. Nurse prescribers have the potential to enhance both access and treatment outcomes. Nurse prescribing practices do, however, vary greatly internationally. The aim of this scoping review is to explore nurse prescribing practices for MOUD globally with a view to informing equitable access and policies for people seeking MOUD. METHODS: This scoping review was informed by the preferred reporting items for systematic reviews and meta-analysis extension for scoping reviews (PRISMA-ScR). Electronic searches from 2010 to date were conducted on the following databases: PsycInfo, PubMed, Embase, and CINAHL. Only studies that met the eligibility criteria and described nurse prescribing policies and/or behaviours for MOUD were included. RESULTS: A total of 22 articles were included in the review which found several barriers and enablers to nurse prescribing of MOUD. Barriers included legislation constraints, lack of professional education and training and the presence of stigmatizing attitudes. Enablers included the presence of existing supportive services, prosocial messaging, and nurse prescriber autonomy. CONCLUSION: The safety and efficacy of nurse prescribing of MOUD is well established, and its expansion can provide a range of advantages to people who are dependent on opiates. This includes increasing access to treatment. Nurse prescribing of MOUD can increase the numbers of people in treatment from 'hard to reach' cohorts such as rural settings, or those with less financial means. It holds significant potential to reduce a wide range of harms and costs associated with high-risk opiate use. To reduce drug-related death and the global burden of harm to individuals, families, and communities, there is an urgent need to address the two key priorities of nurse prescriber legislation and education. Both of which are possible given political and educational commitment.