High-dimensional analysis of 16 SARS-CoV-2 vaccine combinations reveals lymphocyte signatures correlating with immunogenicity.

The range of vaccines developed against severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2) provides a unique opportunity to study immunization across different platforms. In a single-center cohort, we analyzed the humoral and cellular immune compartments following five coronavirus disease 2019 (COVID-19) vaccines spanning three technologies (adenoviral, mRNA and inactivated virus) administered in 16 combinations. For adenoviral and inactivated-virus vaccines, heterologous combinations were generally more immunogenic compared to homologous regimens. The mRNA vaccine as the second dose resulted in the strongest antibody response and induced the highest frequency of spike-binding memory B cells irrespective of the priming vaccine. Priming with the inactivated-virus vaccine increased the SARS-CoV-2-specific T cell response, whereas boosting did not. Distinct immune signatures were elicited by the different vaccine combinations, demonstrating that the immune response is shaped by the type of vaccines applied and the order in which they are delivered. These data provide a framework for improving future vaccine strategies against pathogens and cancer.

L-serine treatment in patients with GRIN-related encephalopathy: a phase 2A, non-randomized study.

GRIN-related disorders are rare developmental encephalopathies with variable manifestations and limited therapeutic options. Here, we present the first non-randomized, open-label, single-arm trial (NCT04646447) designed to evaluate the tolerability and efficacy of L-serine in children with GRIN genetic variants leading to loss-of-function. In this phase 2A trial, patients aged 2-18 years with GRIN loss-of-function pathogenic variants received L-serine for 52 weeks. Primary end points included safety and efficacy by measuring changes in the Vineland Adaptive Behavior Scales, Bayley Scales, age-appropriate Wechsler Scales, Gross Motor Function-88, Sleep Disturbance Scale for Children, Pediatric Quality of Life Inventory, Child Behavior Checklist and the Caregiver-Teacher Report Form following 12 months of treatment. Secondary outcomes included seizure frequency and intensity reduction and EEG improvement. Assessments were performed 3 months and 1 day before starting treatment and 1, 3, 6 and 12 months after beginning the supplement. Twenty-four participants were enrolled (13 males/11 females, mean age 9.8 years, SD 4.8), 23 of whom completed the study. Patients had GRIN2B, GRIN1 and GRIN2A variants (12, 6 and 5 cases, respectively). Their clinical phenotypes showed 91% had intellectual disability (61% severe), 83% had behavioural problems, 78% had movement disorders and 58% had epilepsy. Based on the Vineland Adaptive Behavior Composite standard scores, nine children were classified as mildly impaired (cut-off score > 55), whereas 14 were assigned to the clinically severe group. An improvement was detected in the Daily Living Skills domain (P = 0035) from the Vineland Scales within the mild group. Expressive (P = 0.005), Personal (P = 0.003), Community (P = 0.009), Interpersonal (P = 0.005) and Fine Motor (P = 0.031) subdomains improved for the whole cohort, although improvement was mostly found in the mild group. The Growth Scale Values in the Cognitive subdomain of the Bayley-III Scale showed a significant improvement in the severe group (P = 0.016), with a mean increase of 21.6 points. L-serine treatment was associated with significant improvement in the median Gross Motor Function-88 total score (P = 0.002) and the mean Pediatric Quality of Life total score (P = 0.00068), regardless of severity. L-serine normalized the EEG pattern in five children and the frequency of seizures in one clinically affected child. One patient discontinued treatment due to irritability and insomnia. The trial provides evidence that L-serine is a safe treatment for children with GRIN loss-of-function variants, having the potential to improve adaptive behaviour, motor function and quality of life, with a better response to the treatment in mild phenotypes.

Specific photoreceptor cell fate pathways are differentially altered in NR2E3-associated diseases.

Mutations in NR2E3, a gene encoding an orphan nuclear transcription factor, cause two retinal dystrophies with a distinct phenotype, but the precise role of NR2E3 in rod and cone transcriptional networks remains unclear. To dissect NR2E3 function, we performed scRNA-seq in the retinas of wildtype and two different Nr2e3 mouse models that show phenotypes similar to patients carrying NR2E3 mutations. Our results reveal that rod and cone populations are not homogeneous and can be separated into different sub-classes. We identify a previously unreported cone pathway that generates hybrid cones co-expressing both cone- and rod-related genes. In mutant retinas, this hybrid cone subpopulation is more abundant and includes a subpopulation of rods transitioning towards a cone cell fate. Hybrid photoreceptors with high misexpression of cone- and rod-related genes are prone to regulated necrosis. Overall, our results shed light on the role of NR2E3 in modulating photoreceptor differentiation towards cone and rod fates and explain how different mutations in NR2E3 lead to distinct visual disorders in humans.

Virtual Reality and Serious Videogame-Based Instruments for Assessing Spatial Navigation in Alzheimer's Disease: A Systematic Review of Psychometric Properties.

Over the past decade, research using virtual reality and serious game-based instruments for assessing spatial navigation and spatial memory in at-risk and AD populations has risen. We systematically reviewed the literature since 2012 to identify and evaluate the methodological quality and risk of bias in the analyses of the psychometric properties of VRSG-based instruments. The search was conducted primarily in July-December 2022 and updated in November 2023 in eight major databases. The quality of instrument development and study design were analyzed in all studies. Measurement properties were defined and analyzed according to COSMIN guidelines. A total of 1078 unique records were screened, and following selection criteria, thirty-seven studies were analyzed. From these studies, 30 instruments were identified. Construct and criterion validity were the most reported measurement properties, while structural validity and internal consistency evidence were the least reported. Nineteen studies were deemed very good in construct validity, whereas 11 studies reporting diagnostic accuracy were deemed very good in quality. Limitations regarding theoretical framework and research design requirements were found in most of the studies. VRSG-based instruments are valuable additions to the current diagnostic toolkit for AD. Further research is required to establish the psychometric performance and clinical utility of VRSG-based instruments, particularly the instrument development, content validity, and diagnostic accuracy for preclinical AD screening scenarios. This review provides a straightforward synthesis of the state of the art of VRSG-based instruments and suggests future directions for research.

Recyclable Homogeneous Catalysis Enabled by Dynamic Coordination on Rhodium(II) Axial Sites of Metal-Organic Polyhedra.

The activity of catalytic nanoparticles is strongly dependent on their surface chemistry, which controls colloidal stability and substrate diffusion toward catalytic sites. In this work, we studied how the outer surface chemistry of nanostructured Rh(II)-based metal-organic cages or polyhedra (Rh-MOPs) impacts their performance in homogeneous catalysis. Specifically, through post-synthetic coordination of aliphatic imidazole ligands onto the exohedral Rh(II) axial sites of Rh-MOPs, we solubilized a cuboctahedral Rh-MOP in dichloromethane, thereby enabling its use as a homogeneous catalyst. We demonstrated that the presence of the coordinating ligand on the surface of the Rh-MOP does not hinder its catalytic activity in styrene aziridination and cyclopropanation reactions, thanks to the dynamic Rh-imidazole coordination bond. Finally, we used similar ligand exchange post-synthetic reactions to develop a ligand-mediated approach for precipitating the Rh-MOP catalyst, facilitating the recovery and reuse of Rh-MOPs as homogeneous catalysts.

Incidence and prevalence of headache in influenza: A 2010-2021 surveillance-based study.

BACKGROUND AND PURPOSE: Influenza is a common cause of acute respiratory infection, with headache being one of the symptoms included in the European Commission case definition. The prevalence of headache as a symptom of influenza remains unknown. We aimed to describe the incidence and prevalence of headache in patients with influenza. METHODS: All consecutive patients who met the definition criteria of influenza-like illness during the influenza seasons 2010-2011 through 2021-2022 were included. The seasonal cumulative incidence of influenza per 1000 patients at risk and the prevalence of headache as an influenza symptom were calculated, including the 95% confidence intervals (CIs). Subgroup analyses were done based on patients' sex, age group, microbiological confirmation, vaccination status, and influenza type/subtype/lineage. RESULTS: During the study period, 8171 patients were eligible. The incidence of headache in the context of influenza varied between 0.24 cases per 1000 patients (season 2020-2021) and 21.69 cases per 1000 patients (season 2017-2018). The prevalence of headache was 66.1% (95% CI = 65.1%-67.1%), varying between 49.6% (season 2021-2022) and 80.1% (season 2010-2011). The prevalence of headache was higher in women (67.9% vs. 65.7%, p = 0.03) and higher in patients between 15 and 65 years old. Headache was more prevalent in patients infected with B subtypes than A subtypes (68.7% vs. 56.9%, p < 0.001). There were no notable differences regarding vaccination status or microbiological confirmation of the infection. CONCLUSIONS: Headache is a common symptom in patients with influenza, with a prevalence higher than that observed in other viral infections.

Determinants of Repeating an HIV Test Among Gay, Bisexual, and Other Men Who have Sex with Men, and Transgender People Who Use an Online-Requested Self-Sampling Program and Attending Community-Based Testing Venues in Spain (2018-2021).

Our aims were: (1) to characterize gay, bisexual and other men who have sex with men (GBMSM) and transgender (TG) populations using internet-based self-sampling services in the TESTATE project or attending community-based STI/HIV voluntary counselling and testing (CBVCT) services as alternative strategies to formal HIV testing within the Spanish national health system, and (2) to identify factors associated with repeat use of the same screening strategy from November 2018 to December 2021. Demographic, health, and behavioral characteristics of users using complementary strategies were analyzed. We developed a cross-sectional study, with descriptive analysis, HIV cascade, and a multivariate logistic model to identify factors associated with participants' repeated use of the same screening strategy. We included 9939 users, of whom 94.1% were GBMSM (n = 9348) and 5.9% TG (n = 580), with a high representation of migrants. Reactive results were 3.4% (n = 340), with 3.0% in GBMSM (n = 277/9348) and 10.7% in TG (n = 63/591). 73.8% (n = 251) were confirmed HIV positive and 76.7% (n = 194) were linked to health services. Users repeated the online screening strategy more than CBVCT (44.3% vs. 31.8%), but TG population used face-to-face community services more (8.4% vs. 0.6%). Factors influencing the repetition of the online self-sampling strategy included older age, non-migrant status, and recent HIV testing. In the CBVCT strategy, factors included older age, TG identity, non-migrant status, condom use during the last sexual encounter, and recent HIV testing. In conclusion, both CBVCT and online-requested self-sampling at home are important alternatives to the health system for the provision of HIV testing to GBMSM and TG.

A clinical utility evaluation of dual HIV/Syphilis point-of-care tests in non-clinical settings for screening for HIV and syphilis in men who have sex with men.

BACKGROUND: Dual point-of-care tests (POCTs) for the simultaneous detection of antibodies to HIV and syphilis have been developed. Since community-based organisations (CBO) are effective providers of HIV and syphilis testing among men who have sex with men (MSM), evaluation of the utility of these dual tests at CBO testing services is a high priority. The aim of this study is to determine the feasibility of performing dual HIV-syphilis POCT testing among both users and providers at these non-clinical sites. METHODS: This evaluation assessed the utility of two lateral flow immunochromatographic antibody technologies for dual screening for HIV/syphilis among MSM seeking testing in four CBO testing services in Spain, Slovenia, Latvia, and Ukraine. The study's conceptual framework divides the concept of feasibility into two inter-related domains, acceptability, and usability and further breaks it down into six subdomains: learnability, willingness, suitability, satisfaction, efficacy, and effectiveness. The feasibility analysis was performed by calculating the median score in 3 stages (for individual questions, subdomains, and domains), using a summated scores method. RESULTS: The final sample included 844 participants, 60 of which were found to be HIV test positive (7.1%) and 61 (7.2%) positive on testing for syphilis. There was a small difference (1.1%) when comparing the results of the two dual POCTs under evaluation to the tests routinely used at each site. The inter-rater agreement showed a high concordance between two independent readings. The analysis of the feasibility for the users of the services indicated good satisfaction, suitability, and willingness. In addition, among 18 providers the total mean score showed good acceptability and usability, good willingness, easy learnability, high suitability, and good efficacy, but lower satisfaction and effectiveness. The operational characteristics of both dual study POCTs were well evaluated by providers. CONCLUSIONS: The introduction of dual HIV and syphilis  POCTs in CBO testing services for screening of MSM is feasible, with a high acceptability and usability both for users and providers. Implementation of dual POCTs for HIV and syphilis in CBO testing services is an opportunity for scaling up integrated HIV/syphilis testing for MSM.

Effects of Hand Motor Interventions on Cognitive Outcomes Post-stroke: A Systematic Review and Bayesian Network Meta-analysis.

OBJECTIVE: To synthetize the evidence on the effects of hand rehabilitation (RHB) interventions on cognition post-stroke and compare their efficacy. DATA SOURCES: PubMed, Embase, Cochrane, Scopus, Web of Science, and CINAHL were searched from inception to November 2022. DATA SELECTION: Randomized controlled trials conducted in adults with stroke where the effects of hand motor interventions on any cognitive domains were assessed. DATA EXTRACTION: Data were extracted by 2 independent reviewers. A Bayesian Network Meta-analysis (NMA) was applied for measures with enough studies and comparisons. Risk of bias was assessed with the Cochrane Risk of Bias tool. DATA SYNTHESIS: Fifteen studies were included in qualitative synthesis, and 11 in NMA. Virtual reality (VR) (n=7), robot-assisted (n=5), or handgrip strength (n=3) training were the experimental interventions and conventional RHB (n=14) control intervention. Two separate NMA were performed with MoCA (n=480 participants) and MMSE (n=350 participants) as outcome measures. Both coincided that the most probable best interventions were robot-assisted and strength training, according to SUCRA and rankogram, followed by conventional RHB and VR training. No significant differences between any of the treatments were found in the MoCA network, but in the MMSE, robot-assisted and strength training were significantly better than conventional RHB and VR. No significant differences between robot-assisted and strength training were found nor between conventional RHB and VR. CONCLUSIONS: Motor interventions can improve MoCA/MMSE scores post-stroke. Most probable best interventions were robot-assisted and strength training. Limited literature assessing domain-specific cognitive effects was found.

INDURG TRIAL Protocol: A Randomized Controlled Trial Using Indocyanine Green during Cholecystectomy in Acute Cholecystitis.

INTRODUCTION: Laparoscopic cholecystectomy is one of the most common gastrointestinal surgeries, and bile duct injury is one of its main complications. The use of real-time indocyanine green fluorescence cholangiography allows the identification of extrahepatic biliary structures, facilitating the procedure and reducing the risk of bile duct lesions. A better visualization of the bile duct may help to reduce the need for conversion to open surgery, and may also shorten operating time. The main objective of this study was to determine whether the use of indocyanine green is associated with a reduction in operating time in emergency cholecystectomies. Secondary outcomes are the postoperative hospital stay, the correct intraoperative visualization of the Calot's Triangle structures with the administration of indocyanine green, and the intraoperative complications, postoperative complications and morbidity according to the Clavien-Dindo classification. METHODS: This is a randomized, prospective, controlled, multicenter trial with patients diagnosed with acute cholecystitis requiring emergency cholecystectomy. The control group will comprise 220 patients undergoing emergency laparoscopic cholecystectomy applying the standard technique. The intervention group will comprise 220 patients also undergoing emergency laparoscopic cholecystectomy for acute cholecystitis with prior administration of indocyanine green. CONCLUSION: Due to the lack of published studies on ICG in emergency laparoscopic cholecystectomy, this study may help to establish procedures for its use in the emergency setting.

Trends in Sexual Health of Gay, Bisexual, and Other Men Who Have Sex with Men, and Transgender Individuals: Apps Driven Testing Program for HIV and Other STIs in Barcelona, Spain (2016-2023).

Gay, bisexual and other men who have sex with men (GBMSM) and transgender individuals face heightened risks of HIV and other sexually transmitted infections (STIs). Surveillance within these populations is critical, and community testing services play a pivotal role in preventing and controlling HIV and STIs. This study investigates the trends in HIV, syphilis and hepatitis C (HCV) infections among participants in an apps-driven rapid test program from 2016 to 2023 in Barcelona, Spain, examining associated factors. Trend analysis utilized Wilcoxon-type test and associated factors were determined through multivariate logistic analysis. The prevalence of new HIV diagnosis was 1.81% (CI 1.18-2.64), active syphilis was 3.37% (CI 2.46-4.50) and acute HCV was 0.40% (CI 0.11-1.02). While infection rates showed no significant changes, there was significant increasing in sex work and chemsex and decreasing in condom use. Additionally, a peak in dating apps use for sex and a specific reduction in number of sexual partners were observed in 2020. Factors associated with HIV diagnoses included migrant status (aOR = 11.19; CI 2.58-48.53) and inconsistent condom use during the previous 12 months (aOR = 3.12; CI 1.02-9.51). For syphilis, associated factors were migrant status (aOR = 2.46; CI 1.14-5.29), inconsistent condom use (aOR = 3.38; CI 1.37-8.36), and chemsex practice during the previous 12 months (aOR = 2.80; CI 1.24-6.30). Our findings emphasize the need for tailored interventions, including culturally sensitive outreach for migrants and comprehensive strategies addressing substance use in sexual contexts. Technological innovations and targeted educational initiatives could reduce the burden of HIV and STIs within the GBMSM and transgender communities, providing valuable insights for public health strategies.

Cuidándome: A trauma-informed and cultural adaptation of a chronic disease self-management program for Latina immigrant survivors with a history of adverse childhood experiences and depression or anxiety symptoms.

OBJECTIVES: To develop a cultural and trauma-informed mental health self-management program for immigrant Latina survivors of adverse childhood experiences with depression or anxiety symptoms. METHOD: Guided by Barrera's five-stage process for cultural adaptation, we collaborated with multiple stakeholders including clinical psychologists, community health workers, and Latina immigrant women with a history of adverse childhood experiences and depression or anxiety to transform a chronic disease self-management program to be trauma informed, culturally appropriate, and focus on self-management of depression and anxiety symptoms. RESULTS: Adaptations included translating program materials to Spanish, education on how early life adversity and trauma may impact mental health, virtual delivery, more frequent and shorter sessions, and addition of graphics and written prompts in workbook materials. For the facilitator's manual, culturally relevant vignettes and guidance were added to guide participants through activities and adapt sessions based on participant needs. CONCLUSIONS: Barrera's five-stage process was useful for adapting a program to be both trauma and culturally informed for an underserved population disproportionately affected by trauma and limited access to mental health services. The adaptation demonstrated acceptability with Latina immigrant women and the promise of utilizing unlicensed personnel and technology for increasing the reach of mental health support. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Implementing a New Algorithm for Reinterpretation of Ambiguous Variants in Genetic Dilated Cardiomyopathy.

Dilated cardiomyopathy is a heterogeneous entity that leads to heart failure and malignant arrhythmias. Nearly 50% of cases are inherited; therefore, genetic analysis is crucial to unravel the cause and for the early identification of carriers at risk. A large number of variants remain classified as ambiguous, impeding an actionable clinical translation. Our goal was to perform a comprehensive update of variants previously classified with an ambiguous role, applying a new algorithm of already available tools. In a cohort of 65 cases diagnosed with dilated cardiomyopathy, a total of 125 genetic variants were classified as ambiguous. Our reanalysis resulted in the reclassification of 12% of variants from an unknown to likely benign or likely pathogenic role, due to improved population frequencies. For all the remaining ambiguous variants, we used our algorithm; 60.9% showed a potential but not confirmed deleterious role, and 24.5% showed a potential benign role. Periodically updating the population frequencies is a cheap and fast action, making it possible to clarify the role of ambiguous variants. Here, we perform a comprehensive reanalysis to help to clarify the role of most of ambiguous variants. Our specific algorithms facilitate genetic interpretation in dilated cardiomyopathy.

Duodenal lymphangiomas: endoscopic ultrasound features.

The increasing number of endoscopic explorations help recognize rare lesions of the gastrointestinal tract, such as lymphangiomas, rare benign vascular tumours in adults. Patients with lymphangioma are generally asymptomatic but if complications arise, the approach is endoscopic or surgical. Endoscopic ultrasound aids in distinguishing this tumour from other subepithelial lesions. We present the case of a patient who underwent upper endoscopy and endoscopic ultrasound with findings of two duodenal lymphangiomas.

Factors associated to the presence of headache in patients with influenza infection and its consequences: a 2010-2020 surveillance-based study.

Headache is a common symptom of influenza infection; however, its causes and consequences remain uncertain. In this manuscript, we analyzed which demographic and clinical factors were associated with the presence of headache during the course of influenza infection and whether patients with headache had a different prognosis, evaluated by need of hospitalization, sick leave or school absenteeism. The influence study (NCT05704335) was an observational study that analyzed data routinely collected from the Health Sentinel Network between 2010 and 2020. During the study period, 7832 cases were considered, among which, 5275 (67.4%) reported headache. The presence of headache was independently associated with myalgia (2.753; 95%CI: 2.456-3.087, P < 0.001), asthenia (OR: 1.958; 95%CI: 1.732-2.214, P < 0.001), shivering (OR: 1.925; 95%CI: 1.718-2.156, P < 0.001), nasopharyngeal erythema (OR: 1.505; 95%CI: 1.293-1.753, P < 0.001), fever (OR: 1.469; 95%CI: 1.159-1.861; P = 0.001), sudden onset of symptoms (OR: 1.380; 95%CI: 1.120-1.702, p = 0.004), female sex (OR: 1.134; 95%CI: 1.023-1.257, P = 0.018), and gastrointestinal symptoms (OR: 1.169; 95%CI: 1.039-1.315; P = 0.01). Patients with headache had a sex and age adjusted lower odds of being referred to the hospital (OR: 0.463; 95%CI: 0.264-0.812, P = 0.007) and a higher odd of having a sick leave and/or school absenteeism (absenteeism (OR: 1.342; 95%CI: 1.190-1.514, P < 0.001). In conclusion, the presence of headache seems associated with symptoms caused by the innate immune response. These findings support a headache pathophysiology linked with the innate immune response. Due to the potential negative consequences and its treatable nature, clinicians should systematically evaluate it and, whenever necessary, treat it too.

Intravenous Vitamin C as an Add-on Therapy for the Treatment of Sepsis in an Intensive Care Unit: A Prospective Cohort Study.

Background and Objectives: According to the Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3), sepsis is defined as "life-threatening organ dysfunction caused by a dysregulated host response to infection". The increased presence of free radicals causes an increase in oxidative stress. Vitamin C is an essential water-soluble vitamin with antioxidant activity and immunoregulatory effects that plays a potential role in the treatment of bacterial infections. Our aim was to evaluate the effectiveness of adding vitamin C to the conventional treatment of sepsis to decrease its mortality rate. Materials and Methods: In a prospective cohort study, we included patients with a diagnosis of sepsis and a SOFA score ≥ 9 who were evaluated in an Intensive Care Unit at a secondary-care hospital. According to the intensive care specialist, they were treated using two different strategies: Group 1-patients with sepsis treated with conventional treatment without vitamin C; Group 2-patients with sepsis with the addition of vitamin C to conventional treatment. Results: We included 34 patients with sepsis. The incidence of mortality was 38%, and 47% of patients used vitamin C as an adjuvant to the basic treatment of sepsis. In the basal analyses, patients treated with use of vitamin C compared to patients treated without vitamin C required less use of glucocorticoids (75% vs. 100%, p = 0.039). At follow-up, patients treated without vitamin C had higher mortality than patients treated with vitamin C as an adjuvant for the treatment of sepsis (55.6% vs. 18.8%, p = 0.03). We observed that the use of vitamin C was a protective factor for mortality in patients with sepsis (RR: 0.54, 95% CI: 0.31-0.96, p = 0.03). Conclusions: The use of vitamin C as an adjuvant to treatment decreases the risk of mortality by 46% in patients with sepsis and SOFA ≥ 9 compared to patients treated without vitamin C as an adjuvant to sepsis.

Transanal versus laparoscopic total mesorectal excision for mid and low rectal cancer (Ta-LaTME study): multicentre, randomized, open-label trial.

BACKGROUND: Transanal total mesorectal excision (TaTME) is a minimally invasive surgical technique that tries to avoid conversion to open surgery. However, specific intraoperative complications and local recurrences have cast some doubt on the suitability of the technique. The primary endpoint of the present study was a composite outcome of conversion surgery. Secondary objectives were to assess postoperative recovery, and pathological and oncological outcomes. METHODS: This was a prospective, multicentre, randomized, controlled open-label study of patients diagnosed with mid and low rectal adenocarcinoma who underwent laparoscopic TaTME or laparoscopic total mesorectal excision (LaTME). The TaTME technique comprised intracorporeal resection and anastomosis. Main outcomes were conversion to open surgery. Secondary outcomes were postoperative morbidity, mortality, pathological, oncological results, and survival. Modified intention-to-treat (mITT) and per-protocol analyses were performed. RESULTS: The study was conducted between April 2015 and May 2021. Patients were randomized to the LaTME (57 patients) or TaTME (59) group. Fifty patients from the LaTME group and 55 from the TaTME group were eligible for mITT analysis. The procedure was converted to open surgery in 11 patients (11 per cent): 10 (20 per cent) in the LaTME group and 1 (2 per cent) in the laparoscopic TaTME group (difference 18.8, 95 per cent c.i. 30 to 7; P = 0.003). No significant differences were found in terms of postoperative recovery and morbidity at 30 days; nor were there significant differences in anastomotic leakage, although it was less common in laparoscopic TaTME. With a median follow-up of 39 months, there were three instances of local recurrence (6.1 per cent) in the LaTME group and one (1.8 per cent) in the laparoscopic TaTME group (95 per cent c.i. 60 to 69; P = 0.3). Registration number: NCT02550769 (http://www.clinicaltrials.gov). CONCLUSION: The conversion rate was significantly lower in laparoscopic TaTME than in LaTME. At centres with experienced surgeons, laparoscopic TaTME can avoid conversion to open surgery.

(Bio)Functionalisation of Metal-Organic Polyhedra by Using Click Chemistry.

The surface chemistry of Metal-Organic Polyhedra (MOPs) is crucial to their physicochemical properties because it governs how they interact with external substances such as solvents, synthetic organic molecules, metal ions, and even biomolecules. Consequently, the advancement of synthetic methods that facilitate the incorporation of diverse functional groups onto MOP surfaces will significantly broaden the range of properties and potential applications for MOPs. This study describes the use of copper(I)-catalysed, azide-alkyne cycloaddition (CuAAC) click reactions to post-synthetically modify the surface of alkyne-functionalised cuboctahedral MOPs. To this end, a novel Rh(II)-based MOP with 24 available surface alkyne groups was synthesised. Each of the 24 alkyne groups on the surface of the "clickable" Rh-MOP can react with azide-containing molecules at room temperature, without compromising the integrity of the MOP. The wide substrate catalogue and orthogonal nature of CuAAC click chemistry was exploited to densely functionalise MOPs with diverse functional groups, including polymers, carboxylic and phosphonic acids, and even biotin moieties, which retained their recognition capabilities once anchored onto the surface of the MOP.

Depressive symptoms following traumatic brain injury are associated with resting-state functional connectivity.

BACKGROUND: To determine whether depressive symptoms in traumatic brain injury (TBI) patients were associated with altered resting-state functional connectivity (rs-fc) or voxel-based morphology in brain regions involved in emotional regulation and associated with depression. METHODS: In the present study, we examined 79 patients (57 males; age range = 17-70 years, M ± s.d. = 38 ± 16.13; BDI-II, M ± s.d. = 9.84 ± 8.67) with TBI. We used structural MRI and resting-state fMRI to examine whether there was a relationship between depression, as measured with the Beck Depression Inventory (BDI-II), and the voxel-based morphology or functional connectivity in regions previously identified as involved in emotional regulation in patients following TBI. Patients were at least 4 months post-TBI (M ± s.d. = 15.13 ± 11.67 months) and the severity of the injury included mild to severe cases [Glasgow Coma Scale (GCS), M ± s.d. = 6.87 ± 3.31]. RESULTS: Our results showed that BDI-II scores were unrelated to voxel-based morphology in the examined regions. We found a positive association between depression scores and rs-fc between limbic regions and cognitive control regions. Conversely, there was a negative association between depression scores and rs-fc between limbic and frontal regions involved in emotion regulation. CONCLUSION: These findings lead to a better understanding of the exact mechanisms that contribute to depression following TBI and better inform treatment decisions.

InfluenCEF study: Clinical phenotype and duration of headache attributed to influenza infection.

INTRODUCTION: Headache is a frequent symptom of infections. We aimed to characterize the clinical phenotype and duration of headache attributed to influenza infection. METHODS: Prospective cohort study done in 53 primary care centers between January and April 2023. Patients were included if they had a confirmed influenza diagnosis, were older than 15 years and had a new-onset headache. Patients' demographics, prior medical history, headache phenotype and duration, associated symptoms and patients' outcomes were assessed. The International Classification of Headache Disorders criteria for headache attributed to a systemic viral infection, migraine and tension-type headache were assessed. RESULTS: Of the 478 patients 75 fulfilled eligibility criteria. The mean age was 43, 56% were men, and 27% had a prior headache history. The headache phenotype was a bilateral headache (52%), with frontal topography (48%), pressing quality (61%), moderate intensity, rhinorrhea (79%), nasal congestion (76%), and photophobia (59%). All patients fulfilled headache attributed to acute systemic viral infection criteria, 43% fulfilled migraine criteria and 31% tension-type headache criteria. The median duration of the headache was four (Inter-quartile range: two-six) days. CONCLUSION: The clinical phenotype of headache attributed to influenza infection was similar to other infections, with more pronounced cranial autonomic symptoms. The headache was an early symptom and was self-limited within a few days.Trial Registration: The study protocol is registered in ClinicalTrial.gov (NCT05704335).