Bit by bit toward the diversity of metopids: Description of the genus Pidimetopus n. gen. (Ciliophora: Armophorea).

While metopids (Armophorea: Metopida) represent the most species-rich group of free-living anaerobic ciliates thriving in hypoxic environments, our understanding of their true diversity remains incomplete. Most metopid species are still characterized only morphologically. Particularly, the so-called IAC clade (named in the past after some of the taxa included, Idiometopus, Atopospira, and Clevelandellida), comprising free-living members as well as the endosymbiotic ones (order Clevelandellida), is in serious need of revision. In our study, we establish a new free-living genus in the IAC clade, Pidimetopus n. gen., with descriptions of two new species, P. nanus n. sp., and P. permonicus n. sp., using up-to-date molecular and morphologic methods. The genus is characterized by small cells (up to 75 µm long), not more than 10 adoral membranelles and eight somatic kineties, and usually, four long caudal cilia that can stiffen. In addition to morphologic and molecular characterizations, we also conducted a statistical morphotype analysis of the polymorphic species P. nanus n. sp. We discuss the relevance of the earlier morphologically described species Metopus minor as a putative collective taxon for several small metopids less than 50 µm long.

Nirsevimab immunization's real-world effectiveness in preventing severe bronchiolitis: A test-negative case-control study.

BACKGROUND: Several clinical trials have shown that nirsevimab, an antibody targeting the respiratory syncytial virus (RSV), reduces RSV bronchiolitis requiring admission. In 2023-2024, Catalonia and Andorra adopted immunization strategies for children <6 months and those born during the epidemic season. This study evaluates the effectiveness of nirsevimab in preventing hospitalizations from RSV bronchiolitis. METHODS: In the epidemic season of 2023-2024, a test-negative case-control study was conducted in three hospitals from Catalonia and Andorra. Patients <12 months old admitted with bronchiolitis and tested for RSV using molecular microbiology tests were included. The effectiveness in preventing RSV bronchiolitis hospitalization and severe disease was estimated using multivariate models. Comparisons between immunized, non-immunized, and non-eligible patients were made in prospectively collected epidemiological, clinical, and microbiological variables. RESULTS: Two hundred thirty-four patients were included. RSV was detected in 141/234 (60.2%), being less common in the immunized group (37% vs 75%, p < .001). The rate of immunized patients among those eligible was 59.7%. The estimated effectiveness for RSV-associated lower respiratory tract infection was 81.0% (95% confidence interval: 60.9-90.7), and for preventing severe disease (the need for NIV/CMV), 85.6% (41.7-96.4%). No significant differences by immunization status were observed in patients with RSV concerning viral coinfections, the need for NIV/CMV or length of hospital stay. CONCLUSIONS: This study provides real-world evidence of the effectiveness of nirsevimab in preventing RSV-lower respiratory tract infection hospitalization and severe disease in infants during their first RSV season following a systematic immunization program. Immunized patients did not exhibit a higher rate of viral coinfections nor differences in clinical severity once admitted.

Impact of universal immunization program with monoclonal antibody nirsevimab on reducing the burden of serious bronchiolitis that need pediatric intensive care.

RSV bronchiolitis remains the leading cause of hospitalization in children under 1 year of age. It is estimated that 2-6% of cases will be hospitalized on pediatric intensive care units (PICUs). In October 2023, a universal immunization program with the monoclonal antibody nirsevimab was implemented in Catalonia. The aim of the study was to analyze the impact of the nirsevimab immunization on the burden of bronchiolitis admitted to a PICU and resulting changes in epidemiological, clinical, and microbiological characteristics comparing the pre-nirsevimab (pre-N) with the post-nirsevimab (post-N) period. This was a prospective, descriptive, and observational study. Patients with severe bronchiolitis admitted to reference children's hospital PICU, between September 2010 and February 2024 were included. Demographic and clinical data were collected and viral laboratory etiological diagnosis was carried out. 1531 patients were recruited, 1458 in the pre-N seasons and 73 after its introduction (58% males, median age 52 days), of which 67% were immunized with nirsevimab. The total number of PICU bronchiolitis admissions, the ratio, and the RSV etiology were significantly lower in the post-N period (p = 0.03, p < 0.001, and p = 0.039, respectively). Significant higher age at admission (p < 0.001) and lower hospital length of stay (p < 0.001) was observed comparing pre-N vs. post-N period. CONCLUSION: Nirsevimab appears to have an important impact on reducing the number and length of stay of PICU admissions due to RSV bronchiolitis. WHAT IS KNOWN: • Bronchiolitis is the most common viral infection of the lower respiratory tract in infants. • It represents 13% of the total pediatric intensive care admissions, typically during winter. This is one of the causes that produces a collapse in the health care systems all around the world. WHAT IS NEW: • In October 2023, universal immunization with monoclonal antibody nirsevimab of all children under 6 months of age was started in the majority of autonomous communities in Spain. • Recent publications from the nirsevimab clinical trials have evidenced a high RSV protective effect, but data on its effect on real life patients who require pediatric intensive care unit admission are missing.

Control compounds for preclinical drug-induced liver injury assessment: Consensus-driven systematic review by the ProEuroDILI network.

BACKGROUND & AIMS: Idiosyncratic drug-induced liver injury (DILI) is a complex and unpredictable event caused by drugs, and herbal or dietary supplements. Early identification of human hepatotoxicity at preclinical stages remains a major challenge, in which the selection of validated in vitro systems and test drugs has a significant impact. In this systematic review, we analyzed the compounds used in hepatotoxicity assays and established a list of DILI-positive and -negative control drugs for validation of in vitro models of DILI, supported by literature and clinical evidence and endorsed by an expert committee from the COST Action ProEuroDILI Network (CA17112). METHODS: Following 2020 PRISMA guidelines, original research articles focusing on DILI which used in vitro human models and performed at least one hepatotoxicity assay with positive and negative control compounds, were included. Bias of the studies was assessed by a modified 'Toxicological Data Reliability Assessment Tool'. RESULTS: A total of 51 studies (out of 2,936) met the inclusion criteria, with 30 categorized as reliable without restrictions. Although there was a broad consensus on positive compounds, the selection of negative compounds lacked clarity. 2D monoculture, short exposure times and cytotoxicity endpoints were the most tested, although there was no consensus on drug concentrations. CONCLUSIONS: Extensive analysis highlighted the lack of agreement on control compounds for in vitro DILI assessment. Following comprehensive in vitro and clinical data analysis together with input from the expert committee, an evidence-based consensus-driven list of 10 positive and negative control drugs for validation of in vitro models of DILI is proposed. IMPACT AND IMPLICATIONS: Prediction of human toxicity early in the drug development process remains a major challenge, necessitating the development of more physiologically relevant liver models and careful selection of drug-induced liver injury (DILI)-positive and -negative control drugs to better predict the risk of DILI associated with new drug candidates. Thus, this systematic study has crucial implications for standardizing the validation of new in vitro models of DILI. By establishing a consensus-driven list of positive and negative control drugs, the study provides a scientifically justified framework for enhancing the consistency of preclinical testing, thereby addressing a significant challenge in early hepatotoxicity identification. Practically, these findings can guide researchers in evaluating safety profiles of new drugs, refining in vitro models, and informing regulatory agencies on potential improvements to regulatory guidelines, ensuring a more systematic and efficient approach to drug safety assessment.

Spatially resolved tissue imaging to analyze the tumor immune microenvironment: beyond cell-type densities.

INTRODUCTION: The tissue immune microenvironment is associated with key aspects of tumor biology. The interaction between the immune system and cancer cells has predictive and prognostic potential across different tumor types. Spatially resolved tissue-based technologies allowed researchers to simultaneously quantify different immune populations in tumor samples. However, bare quantification fails to harness the spatial nature of tissue-based technologies. Tumor-immune interactions are associated with specific spatial patterns that can be measured. In recent years, several computational tools have been developed to increase our understanding of these spatial patterns. TOPICS COVERED: In this review, we cover standard techniques as well as new advances in the field of spatial analysis of the immune microenvironment. We focused on marker quantification, spatial intratumor heterogeneity analysis, cell‒cell spatial interaction studies and neighborhood analyses.

Two new HLA-DQB1*03:02:01 variants with substitutions in intron 2: HLA-DQB1*03:02:01:19 and -DQB1*03:02:01:21.

Two different single nucleotide substitutions in intron 2 give rise to novel HLA-DQB1*03:02:01 alleles.

Non-Invasive Monitoring of Microvascular Oxygenation and Reactive Hyperemia using Hybrid, Near-Infrared Diffuse Optical Spectroscopy for Critical Care.

The detection of levels of impairment in microvascular oxygen consumption and reactive hyperemia is vital in critical care. However, there are no practical means for a robust and quantitative evaluation. This paper describes a protocol to evaluate these impairments using a hybrid near-infrared diffuse optical device. The device contains modules for near-infrared time-resolved and diffuse correlation spectroscopies and pulse-oximetry. These modules allow the non-invasive, continuous, and real-time measurement of the absolute, microvascular blood/tissue oxygen saturation (StO2) and the blood flow index (BFI) along with the peripheral arterial oxygen saturation (SpO2). This device uses an integrated, computer-controlled tourniquet system to execute a standardized protocol with optical data acquisition from the brachioradialis muscle. The standardized vascular occlusion test (VOT) takes care of the variations in the occlusion duration and pressure reported in the literature, while the automation minimizes inter-operator differences. The protocol we describe focuses on a 3-min occlusion period but the details described in this paper can readily be adapted to other durations and cuff pressures, as well as other muscles. The inclusion of an extended baseline and post-occlusion recovery period measurement allows the quantification of the baseline values for all the parameters and the blood/tissue deoxygenation rate that corresponds to the metabolic rate of oxygen consumption. Once the cuff is released, we characterize the tissue reoxygenation rate, magnitude, and duration of the hyperemic response in BFI and StO2. These latter parameters correspond to the quantification of the reactive hyperemia, which provides information about the endothelial function. Furthermore, the above-mentioned measurements of the absolute concentration of oxygenated and deoxygenated hemoglobin, BFI, the derived metabolic rate of oxygen consumption, StO2, and SpO2 provide a yet-to-be-explored rich data set that can exhibit disease severity, personalized therapeutics, and management interventions.

Reconstruction Using Perforator Propeller Flaps After Malignant Melanoma Resection of the Lower Extremity.

Introduction: Surgical excision with margin of 2 cm is the treatment of choice in malignant cutaneous melanoma when Breslow index is >1 mm. When located on the lower limb, these resections can lead to large defects that require complex reconstruction in order to salvage the limb. The use of propeller-perforator flaps has multiple advantages such as the preservation of adjacent muscles, decrease in morbidity in the donor site, and good aesthetic and functional results. Our objective is to expose our experience and results with the use of propeller-perforator flaps for coverage of this kind of defects. Materials and Methods: Patients with malignant cutaneous melanoma of the lower limb who required reconstruction with a propeller-perforator flap between the years 2015 and 2021 in our plastic surgery department were included in this retrospective research. Demographic, reconstructive, oncologic, and functional data were collected and analyzed. Results: The cohort of 22 patients showed 100% of successful reconstructive outcomes. Only 2 patients experienced distal necrosis of the flap that was resolved with local dressings. Fast recovery and early capacity to walk were achieved in the majority of the patients with an average of 10.1 days until weight-baring walking. The 2-year overall and progression-free survival rates were 86.37% and 81.82%, respectively. Conclusion: The use of propeller perforator flaps for oncological defects coverage in the lower limb location has to be considered as a reliable choice as it takes less surgical time and a faster recovery. It allows limb salvage with an adequate length and functionality, with minimal donor site morbidity and a lower index of complications, contributing to improve patient's quality of life and not delaying other oncological treatments.

Introduction: Une excision chirurgicale aux marges de 2 cm est le traitement de première intention des mélanomes cutanés malins lorsque l'indice de Breslow est supérieur à 1 mm. Situées sur un membre inférieur, ces résections peuvent provoquer de grosses anomalies qui exigent une reconstruction complète pour sauver le membre. Le recours aux lambeaux perforants en hélice comporte de multiples avantages, tels que la préservation des muscles adjacents, la diminution des problèmes médicaux au foyer du donneur ainsi que des résultats esthétiques et fonctionnels satisfaisants. Les auteurs visent à présenter leur expérience et leurs résultats lorsqu'ils recouvrent ce type d'anomalie à l'aide de lambeaux perforants en hélice. Matériel et méthodologie: Les patients atteints d'un mélanome cutané malin d'un membre inférieur qui nécessitaient une reconstruction à l'aide d'un lambeau perforant en hélice entre 2015 et 2021 au département de chirurgie plastique des auteurs ont été inclus dans la présente recherche rétrospective. Les auteurs ont recueilli et analysé les caractéristiques démographiques ainsi que les données reconstructives, oncologiques et fonctionnelles des patients. Résultats: Les résultats reconstructifs ont été satisfaisants dans toute la cohorte de 22 patients. Seuls deux d'entre eux ont vécu une nécrose distale du lambeau, qui a été corrigée par des pansements locaux. La majorité des patients se sont remis rapidement et ont pu recommencer à marcher tôt, soit en moyenne au bout de 10,1 jours avec mise en charge. Le taux de survie global et le taux d'absence de détérioration au bout de deux ans s'élevaient à 86,37 % et à 81,82 %, respectivement. Conclusion: Le recours à des lambeaux perforants en hélice pour couvrir des anomalies oncologiques du membre inférieur doit être considéré comme un choix fiable, car l'intervention chirurgicale et la convalescence sont plus courtes. Cette intervention permet de sauver le membre, dont la longueur et la fonction demeurent appropriées, elle est associée à des problèmes médicaux minimes au foyer du donneur et à un faible indice de complications, elle contribue à améliorer la qualité de vie du patient et elle ne retarde pas les autres traitements oncologiques.

Vulnerable at rest? A resting-state EEG study and psychosocial factors of young adult offspring of alcohol-dependent parents.

BACKGROUND: Offspring of parents with alcohol use disorder (AUD) are more susceptible to developing AUD, with an estimated heritability of around 50%. Vulnerability to AUD in first-degree relatives is influenced by biological factors, such as spontaneous brain activity, and high-risk psychosocial characteristics. However, existing resting-state EEG studies in AUD offspring have shown inconsistent findings regarding theta, alpha, and beta band frequencies. Additionally, research consistently demonstrates an increased risk of internalizing and externalizing disorders, self-regulation difficulties, and interpersonal issues among AUD offspring. METHODS: This study aimed to investigate the absolute power of theta, alpha, and beta frequencies in young adult offspring with a family history of AUD compared to individuals without family history. The psychosocial profiles of the offspring were also examined in relation to individuals without a family history of AUD. Furthermore, the study sought to explore the potential association between differences in frequency bands and psychosocial variables. Resting-state EEG recordings were obtained from 31 young adult healthy offspring of alcohol-dependent individuals and 43 participants with no family history of AUD (age range: 16-25 years). Participants also completed self-report questionnaires assessing anxiety and depressive symptoms, impulsivity, emotion regulation, and social involvement. RESULTS: The results revealed no significant differences in spontaneous brain activity between the offspring and participants without a family history of AUD. However, in terms of psychosocial factors, the offspring exhibited significantly lower social involvement than the control group. CONCLUSIONS: This study does not provide evidence suggesting vulnerability in offspring based on differences in spontaneous brain activity. Moreover, this investigation highlights the importance of interventions aimed at enhancing social connections in offspring. Such interventions can not only reduce the risk of developing AUD, given its strong association with increased feelings of loneliness but also improve the overall well-being of the offspring.

Examining Profiles and Treatment Outcomes in Dual Diagnosis: Comparison of Coordinated Treatment With Mental Health Services Versus Addiction Center Alone. A Real-World Data Analysis.

OBJECTIVE: The aim of this work was to examine the profile and treatment outcomes of patients with dual pathology depending on whether the patients were attending addiction centers or are being treated in a coordinated model by mental health services. METHODS: Data from 7225 dual diagnosis patients were used, of whom 2417 (33.5%) received treatment in the mental health coordinated modality. Clinical information was taken from the patients' electronic health record. RESULTS: Differences were found in patients' sociodemographic and comorbidity profiles according to treatment modality. In general, coordinated care yielded favorable outcomes (higher attendance and lower dropout rates but no differences in retention). The logistic regression analysis identified predictors of patient profiles in coordinated care, emphasizing having a severe mental health disorder (OR = 3.878, 95% CI [3.443, 4.368]; p = .000), being referred by social/health services, or having retired status. Main differences were observed according to the comorbid diagnosis presented, particularly in cases in which the patient had impulse control, hyperkinetic, or cluster C personality disorder. CONCLUSIONS: While therapeutic outcomes are influenced by associated comorbidities, the disorders prognosis can be favorable with appropriate treatment. Furthermore, analysis of differences according to treatment modality allows for predicting the type of patient who will receive a particular service, which enables the development of tailored treatments.

Effects of transcutaneous radiofrequency diathermy versus ultrasound on latent myofascial trigger points in the upper trapezius: A randomized crossover trial.

BACKGROUND: Currently, the use of radiofrequency diathermy for the treatment of neck pain is booming. OBJECTIVE: This study aimed to evaluate the clinical efficacy of Digital Capacitive Diathermy (DCD®) on stiffness, pain, cervical range of motion, and cervical disability and to compare it with ultrasound (US) in patients with latent myofascial trigger point (MTrP) in the upper trapezius. METHODS: Nineteen participants with latent MTrPs in the upper trapezius were included in the assessor-masked, randomized, clinical crossover trial. Subjects were exposed to both interventions: US and DCD® and treatment effectiveness was measured by myotonometric variables, pressure pain threshold (PPT), visual analog scale (VAS), cervical side-bending flexion ranges, and the neck disability index scale (NDI). RESULTS: There were no significant differences between US and DCD® interventions regarding changes in outcome measures. The US group achieved a statistically significant difference of 2.16 to 1.13 points (p= 0.005; r= 0.646) for the VAS. The DCD® intervention showed a statistically significant improvement of 1.11 points for the NDI at 1-week following intervention (95% CI 0.14-2.07; p= 0.27; d= 0.217). CONCLUSION: Our findings suggest that DCD® and US can both be considered effective modalities for the treatment of latent MTrPs, having a longer duration of action with DCD® therapy.

Lettre to editor: Case report of an ictal asystole as debut in new onset epilepsy.

The case report describes a 65-year-old man with arterial hypertension and a metallic aortic valve who presented to the emergency room for a loss of consciousness event and memory impairment. The electroencephalographic recording showed right temporal epileptiform activity followed by a 9 s asystole with quick consciousness recovery. The patient was diagnosed with right temporal epilepsy with asystole and was prescribed levetiracetam to prevent new events. A pacemaker was indicated in the follow-up for the long duration of the asystole, preventing major morbidity. Ictal asystole (IA) is a rare phenomenon of epilepsy that leads to syncope. It is observed in focal epilepsy, especially in left temporal epilepsy. Underlying cardiac pathology may facilitate IA, especially when the onset of the epilepsy is new. Knowledge of focal temporal semiology is key, concerning our case report, the memory impairment points to temporal pathology, and ictal vomiting in the non-dominant hemisphere. Anti-seizures drugs must be initiated in all patients, and there is a recommendation to avoid those with negative inotropic and arrhythmogenic effects (such as phenytoin, carbamazepine, and lacosamide). There is a discussion about pacemaker indication, however, it is highly recommended in non-controlled epilepsy and in ictal asystoles that last for more than 6 s to reduce morbidity.

Modeling the Therapeutic Process of Patients with Cocaine Use Disorders: A Guide for Predicting Readmission.

INTRODUCTION: Patients with cocaine use disorders have very high readmission rates. Our aim was to model the relationships between attributes of patients with cocaine use disorder at the beginning of treatment, therapeutic process indicators of time in treatment or proportion of appointments attended, and treatment outcomes, including outcomes at discharge and non-readmissions posttreatment as indicators of therapeutic success. METHOD: A retrospective observational design was used with 10,298 cocaine use disorder patients. Electronic health records were used for statistical analysis of the data. Randomized subsample 1 (n = 5,150) was used for exploratory analysis and subsample 2 (n = 5,148) for modeling relationships between the variables. RESULTS: Patients attributes at intake (e.g., legal services as the source of referral) were of limited significance in explaining time in treatment, proportion of appointments attended, and treatment outcomes. Time in treatment and proportion of appointments attended emerged as significant factors in explaining outcomes at discharge. However, readmissions were primarily explained by time in treatment and outcomes at discharge, although referrals to addiction centers by health services also appeared to be relevant for explaining readmission. DISCUSSION/CONCLUSION: Our study has shown that maintaining a sufficient appointment attendance rate and remaining in treatment for a longer duration are critical therapeutic process indicators for explaining outcomes at the point of discharge and therapeutic success, as indicated by a reduced likelihood of readmissions. Patients who remained in treatment for an extended period were found to have a reduced risk of future readmissions. In addition, our study highlights the importance of maintaining a satisfactory appointment attendance rate to attain successful short- and medium-term therapeutic discharge outcomes. These guidelines could help to increase the efficiency of patient treatment and alleviate the suffering of both patients and their families.

Detection of two HLA-B*35 variants: HLA-B*35:01:01:39 and -B*35:03:01:32.

Two nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-B*35:01:01:39 and -B*35:03:01:32.

Discovery of three HLA-DQB1*03:01:01 variants: HLA-DQB1*03:01:01:54, -DQB1*03:01:01:56 and -DQB1*03:01:01:58.

Three nucleotide substitutions in intronic regions give rise to the novel alleles: HLA-DQB1*03:01:01:54, -DQB1*03:01:01:56, -DQB1*03:01:01:58.

HLA-DPA1*02:01:25, a novel allele with a synonymous transition in exon 2 identified by next-generation sequencing.

HLA-DPA1*02:01:25 differs from DPA1*02:01:01:02 by a synonymous transition in exon 2.