Insights into Land Plant Evolution Garnered from the Marchantia polymorpha Genome.

The evolution of land flora transformed the terrestrial environment. Land plants evolved from an ancestral charophycean alga from which they inherited developmental, biochemical, and cell biological attributes. Additional biochemical and physiological adaptations to land, and a life cycle with an alternation between multicellular haploid and diploid generations that facilitated efficient dispersal of desiccation tolerant spores, evolved in the ancestral land plant. We analyzed the genome of the liverwort Marchantia polymorpha, a member of a basal land plant lineage. Relative to charophycean algae, land plant genomes are characterized by genes encoding novel biochemical pathways, new phytohormone signaling pathways (notably auxin), expanded repertoires of signaling pathways, and increased diversity in some transcription factor families. Compared with other sequenced land plants, M. polymorpha exhibits low genetic redundancy in most regulatory pathways, with this portion of its genome resembling that predicted for the ancestral land plant. PAPERCLIP.

A bistable circuit involving SCARECROW-RETINOBLASTOMA integrates cues to inform asymmetric stem cell division.

In plants, where cells cannot migrate, asymmetric cell divisions (ACDs) must be confined to the appropriate spatial context. We investigate tissue-generating asymmetric divisions in a stem cell daughter within the Arabidopsis root. Spatial restriction of these divisions requires physical binding of the stem cell regulator SCARECROW (SCR) by the RETINOBLASTOMA-RELATED (RBR) protein. In the stem cell niche, SCR activity is counteracted by phosphorylation of RBR through a cyclinD6;1-CDK complex. This cyclin is itself under transcriptional control of SCR and its partner SHORT ROOT (SHR), creating a robust bistable circuit with either high or low SHR-SCR complex activity. Auxin biases this circuit by promoting CYCD6;1 transcription. Mathematical modeling shows that ACDs are only switched on after integration of radial and longitudinal information, determined by SHR and auxin distribution, respectively. Coupling of cell-cycle progression to protein degradation resets the circuit, resulting in a "flip flop" that constrains asymmetric cell division to the stem cell region.

MGnify: the microbiome sequence data analysis resource in 2023.

The MGnify platform (https://www.ebi.ac.uk/metagenomics) facilitates the assembly, analysis and archiving of microbiome-derived nucleic acid sequences. The platform provides access to taxonomic assignments and functional annotations for nearly half a million analyses covering metabarcoding, metatranscriptomic, and metagenomic datasets, which are derived from a wide range of different environments. Over the past 3 years, MGnify has not only grown in terms of the number of datasets contained but also increased the breadth of analyses provided, such as the analysis of long-read sequences. The MGnify protein database now exceeds 2.4 billion non-redundant sequences predicted from metagenomic assemblies. This collection is now organised into a relational database making it possible to understand the genomic context of the protein through navigation back to the source assembly and sample metadata, marking a major improvement. To extend beyond the functional annotations already provided in MGnify, we have applied deep learning-based annotation methods. The technology underlying MGnify's Application Programming Interface (API) and website has been upgraded, and we have enabled the ability to perform downstream analysis of the MGnify data through the introduction of a coupled Jupyter Lab environment.

Systemic messenger RNA replacement therapy is effective in a novel clinically relevant model of acute intermittent porphyria developed in non-human primates.

OBJECTIVE: Acute intermittent porphyria (AIP) is a rare metabolic disorder caused by haploinsufficiency of hepatic porphobilinogen deaminase (PBGD), the third enzyme of the heme biosynthesis. Individuals with AIP experience neurovisceral attacks closely associated with hepatic overproduction of potentially neurotoxic heme precursors. DESIGN: We replicated AIP in non-human primates (NHPs) through selective knockdown of the hepatic PBGD gene and evaluated the safety and therapeutic efficacy of human PBGD (hPBGD) mRNA rescue. RESULTS: Intrahepatic administration of a recombinant adeno-associated viral vector containing short hairpin RNA against endogenous PBGD mRNA resulted in sustained PBGD activity inhibition in liver tissue for up to 7 months postinjection. The administration of porphyrinogenic drugs to NHPs induced hepatic heme synthesis, elevated urinary porphyrin precursors and reproduced acute attack symptoms in patients with AIP, including pain, motor disturbances and increased brain GABAergic activity. The model also recapitulated functional anomalies associated with AIP, such as reduced brain perfusion and cerebral glucose uptake, disturbances in hepatic TCA cycle, one-carbon metabolism, drug biotransformation, lipidomic profile and abnormal mitochondrial respiratory chain activity. Additionally, repeated systemic administrations of hPBGD mRNA in this AIP NHP model restored hepatic PBGD levels and activity, providing successful protection against acute attacks, metabolic changes in the liver and CNS disturbances. This approach demonstrated better efficacy than the current standards of care for AIP. CONCLUSION: This novel model significantly expands our understanding of AIP at the molecular, biochemical and clinical levels and confirms the safety and translatability of multiple systemic administration of hPBGD mRNA as a potential aetiological AIP treatment.

Polarized sorting of Patched enables cytoneme-mediated Hedgehog reception in the Drosophila wing disc.

Hedgehog (Hh) signal molecules play a fundamental role in development, adult stem cell maintenance and cancer. Hh can signal at a distance, and we have proposed that its graded distribution across Drosophila epithelia is mediated by filopodia-like structures called cytonemes. Hh reception by Patched (Ptc) happens at discrete sites along presenting and receiving cytonemes, reminiscent of synaptic processes. Here, we show that a vesicle fusion mechanism mediated by SNARE proteins is required for Ptc placement at contact sites. Transport of Ptc to these sites requires multivesicular bodies (MVBs) formation via ESCRT machinery, in a manner different to that regulating Ptc/Hh lysosomal degradation after reception. These MVBs include extracellular vesicle (EV) markers and, accordingly, Ptc is detected in the purified exosomal fraction from cultured cells. Blockage of Ptc trafficking and fusion to basolateral membranes result in low levels of Ptc presentation for reception, causing an extended and flattened Hh gradient.

In vitro activity of cefiderocol in Pseudomonas aeruginosa isolates from people with cystic fibrosis recovered during three multicentre studies in Spain.

OBJECTIVES: Despite the introduction of cystic fibrosis transmembrane conductance regulator (CFTR) modulators, Pseudomonas aeruginosa is still a major pathogen in people with cystic fibrosis (pwCF). We determine the activity of cefiderocol and comparators in a collection of 154 P. aeruginosa isolates recovered from pwCF during three multicentre studies performed in 17 Spanish hospitals in 2013, 2017 and 2021. METHODS: ISO broth microdilution was performed and MICs were interpreted with CLSI and EUCAST criteria. Mutation frequency and WGS were also performed. RESULTS: Overall, 21.4% were MDR, 20.8% XDR and 1.3% pandrug-resistant (PDR). Up to 17% of the isolates showed a hypermutator phenotype. Cefiderocol demonstrated excellent activity; only 13 isolates (8.4%) were cefiderocol resistant by EUCAST (none using CLSI). A high proportion of the isolates resistant to ceftolozane/tazobactam (71.4%), meropenem/vaborbactam (70.0%), imipenem/relebactam (68.0%) and ceftazidime/avibactam (55.6%) were susceptible to cefiderocol. Nine out of 13 cefiderocol-resistant isolates were hypermutators (P < 0.001). Eighty-three STs were detected, with ST98 being the most frequent. Only one isolate belonging to the ST175 high-risk clone carried blaVIM-2. Exclusive mutations affecting genes involved in membrane permeability, AmpC overexpression (L320P-AmpC) and efflux pump up-regulation were found in cefiderocol-resistant isolates (MIC = 4-8 mg/L). Cefiderocol resistance could also be associated with mutations in genes related to iron uptake (tonB-dependent receptors and pyochelin/pyoverdine biosynthesis). CONCLUSIONS: Our results position cefiderocol as a therapeutic option in pwCF infected with P. aeruginosa resistant to most recent ß-lactam/ß-lactamase inhibitor combinations.

The outcome of boosting mitochondrial activity in alcohol-associated liver disease is organ-dependent.

BACKGROUND AND AIMS: Alcohol-associated liver disease (ALD) accounts for 70% of liver-related deaths in Europe, with no effective approved therapies. Although mitochondrial dysfunction is one of the earliest manifestations of alcohol-induced injury, restoring mitochondrial activity remains a problematic strategy due to oxidative stress. Here, we identify methylation-controlled J protein (MCJ) as a mediator for ALD progression and hypothesize that targeting MCJ may help in recovering mitochondrial fitness without collateral oxidative damage. APPROACH AND RESULTS: C57BL/6 mice [wild-type (Wt)] Mcj knockout and Mcj liver-specific silencing (MCJ-LSS) underwent the NIAAA dietary protocol (Lieber-DeCarli diet containing 5% (vol/vol) ethanol for 10 days, plus a single binge ethanol feeding at day 11). To evaluate the impact of a restored mitochondrial activity in ALD, the liver, gut, and pancreas were characterized, focusing on lipid metabolism, glucose homeostasis, intestinal permeability, and microbiota composition. MCJ, a protein acting as an endogenous negative regulator of mitochondrial respiration, is downregulated in the early stages of ALD and increases with the severity of the disease. Whole-body deficiency of MCJ is detrimental during ALD because it exacerbates the systemic effects of alcohol abuse through altered intestinal permeability, increased endotoxemia, and dysregulation of pancreatic function, which overall worsens liver injury. On the other hand, liver-specific Mcj silencing prevents main ALD hallmarks, that is, mitochondrial dysfunction, steatosis, inflammation, and oxidative stress, as it restores the NAD + /NADH ratio and SIRT1 function, hence preventing de novo lipogenesis and improving lipid oxidation. CONCLUSIONS: Improving mitochondrial respiration by liver-specific Mcj silencing might become a novel therapeutic approach for treating ALD.

Pigmented acuminated condylomas seborrhoeic keratosis-like: a new entity?

BACKGROUND: Condyloma acuminatum is caused by human papillomavirus (HPV), which typically presents as excrescent, pedunculated, papillomatous lesions which may be of a pale colour. On rare occasions, we have observed pigmented genital lesions that are similar to seborrhoeic keratoses, but with histological findings of condyloma acuminatum and positive genotyping for HPV. We have termed these 'seborrhoeic keratosis-like' type condylomas. METHODS: This is an observational retrospective study. The following clinical data were collected: age, sex, time of evolution, location, isolated or multiple lesions, monomorphous or polymorphous/mixed lesions. HPV genotyping was performed in all cases, and excision for histological study in eight cases. RESULTS: A total of 31 patients were diagnosed with this type of pigmented condylomata acuminata. Of these, 16 had isolated lesions (less than five lesions) and 15 had multiple lesions. 67% of the lesions exhibited slow growth, with an evolution period of greater than 1 year. The most frequent location was the base of the penis and pubis. HPV genotyping of the lesions was positive in all cases, with the HPV-6 genotype predominating (28 cases, 90.3%). The lesions exhibited dermoscopic differences from other pigmented lesions and histological findings attributable to HPV infection (pseudoparakeratosis, koilocytosis, etc) and others similar to those observed in seborrhoeic keratoses. CONCLUSIONS: A total of 31 patients were diagnosed with pigmented verrucous lesions, excrescents, isolated or multiple, in the genital region. These lesions exhibited clinical characteristics similar to seborrhoeic keratoses, with positive genotyping for HPV. In the majority of cases, the genotype was HPV-6. These lesions have been named 'pigmented condylomata acuminata seborrhoeic keratosis-like'. Only 10 cases of these lesions have been described in the literature.

Predictors of permanent pacemaker implantation for transcatheter self-expandable aortic valve implant in the cusp overlap era.

BACKGROUND: Predictors of permanent pacemaker implantation (PPMI) after self-expanding transcatheter aortic valve implant (TAVI) were described. Is unknown if PPMI predictors remain in the era of high implants using the cusp overlap (COP). METHODS: Single-center, prospective, consecutive case series of patients undergoing self-expanding TAVI with the COP approach. The status of PPMI and other clinical events were ascertained at 30 days. RESULTS: A total of 261 patients were included (84% with Evolut, n = 219). Implant depth >4 mm was infrequent (13.8%). TAVI depth (OR 1.259; p = 0.005), first or second-degree auriculo-ventricular block (OR 3.406; p = 0.033), right-bundle (OR 15.477; p < 0.0001), and incomplete left-bundle branch block (OR 7.964; p = 0.036) were found to be independent predictors of PPMI. The risk of PPMI with deep implant and no electrical disturbances was 3%, and 0% with high implant and no prior electrical disturbances. Those who received PPMI had no statistically significant increased risk of death, myocardial infarction, stroke, bleeding events, or vascular complications at 30 days, but longer hospital stay (mean difference 1.43 days more, p = 0.003). CONCLUSIONS: Implant depth and prior conduction abnormalities remain the main predictors of PPMI using self-expanding TAVI in the COP era. Patients with high implants and no prior conduction abnormalities may be candidates for early discharge after uneventful self-expanding TAVI, while the rest may need inpatient monitoring regardless of achieving a high implant. The need for PPMI was associated with longer hospital stays.

Borrelia burgdorferi infection induces long-term memory-like responses in macrophages with tissue-wide consequences in the heart.

Lyme carditis is an extracutaneous manifestation of Lyme disease characterized by episodes of atrioventricular block of varying degrees and additional, less reported cardiomyopathies. The molecular changes associated with the response to Borrelia burgdorferi over the course of infection are poorly understood. Here, we identify broad transcriptomic and proteomic changes in the heart during infection that reveal a profound down-regulation of mitochondrial components. We also describe the long-term functional modulation of macrophages exposed to live bacteria, characterized by an augmented glycolytic output, increased spirochetal binding and internalization, and reduced inflammatory responses. In vitro, glycolysis inhibition reduces the production of tumor necrosis factor (TNF) by memory macrophages, whereas in vivo, it produces the reversion of the memory phenotype, the recovery of tissue mitochondrial components, and decreased inflammation and spirochetal burdens. These results show that B. burgdorferi induces long-term, memory-like responses in macrophages with tissue-wide consequences that are amenable to be manipulated in vivo.

Short- and mid-term morbidity and primary-care burden due to infant respiratory syncytial virus infection: A Spanish 6-year population-based longitudinal study.

BACKGROUND: The morbidity burden of respiratory syncytial virus (RSV) in infants extends beyond hospitalization. Defining the RSV burden before implementing prophylaxis programs is essential for evaluating any potential impact on short- to mid-term morbidity and the utilization of primary healthcare (PHC) and emergency services (ES). We established this reference data using a population-based cohort approach. METHODS: Infants hospitalized for RSV from January 2016 to March 2023 were matched with non-hospitalized ones based on birthdate and sex. We defined the exposure as severe RSV hospitalization. The main study outcomes were as follows: (1) PHC and ES visits for RSV, categorized using the International Classification of Primary Care codes, (2) prescriptions for respiratory airway obstructive disease, and (3) antibacterial prescriptions. Participants were followed up from 30 days before hospitalization for severe RSV until the outcome occurrence or end of the study. Adjusted incidence rate ratios (IRRs) of the outcomes along with their 95% confidence intervals (CI) were estimated using Poisson regression models. Stratified analyses by type of PHC visit (nurse, pediatrician, or pharmacy) and follow-up period were undertaken. We defined mid-term outcomes as those taking place up to 24 months of follow-up period. RESULTS: The study included 6626 children (3313 RSV-hospitalized; 3313 non-hospitalized) with a median follow-up of 53.7 months (IQR = 27.9, 69.4). After a 3-month follow-up, severe RSV was associated with a considerable increase in PHC visits for wheezing/asthma (IRR = 4.31, 95% CI: 3.84-4.84), lower respiratory infections (IRR = 4.91, 95% CI: 4.34-5.58), and bronchiolitis (IRR = 4.68, 95% CI: 2.93-7.65). Severe RSV was also associated with more PHC visits for the pediatrician (IRR = 2.00, 95% CI: 1.96-2.05), nurse (IRR = 1.89, 95% CI: 1.75-1.92), hospital emergency (IRR = 2.39, 95% CI: 2.17-2.63), primary healthcare emergency (IRR: 1.54, 95% CI: 1.31-1.82), as well as with important increase in prescriptions for obstructive airway diseases (IRR = 5.98, 95% CI: 5.43-6.60) and antibacterials (IRR = 4.02, 95% CI: 3.38-4.81). All findings remained substantial until 2 years of post-infection. CONCLUSIONS: Severe RSV infection in infants significantly increases short- to mid-term respiratory morbidity leading to an escalation in healthcare utilization (PHC/ES attendance) and medication prescriptions for up to 2 years afterward. Our approach could be useful in assessing the impact and cost-effectiveness of RSV prevention programs.

Exploring the interplay of frailty, physical function, physical activity, nutritional status, and their association with quality of life and depressive symptoms in older adults with the frailty phenotype.

OBJECTIVE: This study aimed to explore the interplay between frailty, physical function, physical activity, nutritional status, and their impact on the quality of life and depressive status in older adults with frailty. METHODS: A cross-sectional study involving 235 pre-frail/frail older adults residing in Spanish communities was conducted. Frailty was assessed using Fried's criteria, physical function was evaluated using the Short Physical Performance Battery, and physical activity levels were measured via wrist-worn accelerometers. Nutritional status was determined using the Mini-Nutritional Assessment alongside anthropometric measurements. Quality of life was gauged using the EuroQoL 5-Dimension 5-Level, while depressive status was assessed using the Yesavage 15-item Geriatric Depression Scale. Multivariate linear regression and logistic regression analyses were employed to elucidate the associations of these factors with quality of life and depression. RESULTS: Our findings revealed significant correlations between various factors and quality of life. Notably, reported fatigue (ß = -0.276, p = 0.002), performance in the 4-m gait test (ß = -0.242, p = 0.001), the score on the short version of the Mini-Nutritional Assessment (ß = 0.312, p = 0.002), and engagement in light physical activity (ß = 0.180, p = 0.023) were all found to be associated with quality of life. In terms of depressive symptoms, the Mini-Nutritional Assessment score emerged as a protective factor (Odds ratio, OR: 0.812, p < 0.001), as did participation in moderate physical activity (OR: 0.988, p = 0.028). Conversely, fatigue (OR: 3.277, p = 0.003) and a slow gait speed (OR: 1.136, p = 0.045) were identified as risk factors for depressive symptoms. CONCLUSIONS: This study underscores the detrimental association of fatigue and slow gait speed on both quality of life and depressive status among older adults with frailty. In contrast, engaging in physical activity and addressing malnutrition risk emerge as critical protective factors for enhancing quality of life and ameliorating depressive symptoms in this population. CLINICAL TRIAL REGISTRATION: This is a study that uses cross-sectional data from a trial registered at ClinicalTrials.gov (Identifier: NCT05610605).

Outcomes of initially nonoperative management of diverticulitis with abscess formation in immunosuppressed patients. DIPLICAB study COLLABORATIVE group.

AIM: Management of diverticulitis with abscess formation in immunosuppressed patients (IMS) remains unclear. The main objective of the study was to assess short- and long-term outcomes between IMS and immunocompetent patients (IC). The secondary aim was to identify risk factors for emergency surgery. METHODS: A nationwide retrospective cohort study was performed at 29 Spanish referral centres between 2015-2019 including consecutive patients with first episode of diverticulitis classified as modified Hinchey Ib or II. IMS included immunosuppressive therapy, biologic therapy, malignant neoplasm with active chemotherapy and chronic steroid therapy. A multivariate analysis was performed to identify independent risk factors to emergency surgery in IMS. RESULTS: A total of 1395 patients were included; 118 IMS and 1277 IC. There were no significant differences in emergency surgery between IMS and IC (19.5% and 13.5%, p = 0.075) but IMS was associated with higher mortality (15.1% vs. 0.6%, p < 0.001). Similar recurrent episodes were found between IMS and IC (28% vs. 28.2%, p = 0.963). Following multivariate analysis, immunosuppressive treatment, p = 0.002; OR: 3.35 (1.57-7.15), free gas bubbles, p < 0.001; OR: 2.91 (2.01-4.21), Hinchey II, p = 0.002; OR: 1.88 (1.26-2.83), use of morphine, p < 0.001; OR: 3.08 (1.98-4.80), abscess size ≥5 cm, p = 0.001; OR: 1.97 (1.33-2.93) and leucocytosis at third day, p < 0.001; OR: 1.001 (1.001-1.002) were independently associated with emergency surgery in IMS. CONCLUSION: Nonoperative management in IMS has been shown to be safe with similar treatment failure than IC. IMS presented higher mortality in emergency surgery and similar rate of recurrent diverticulitis than IC. Identifying risk factors to emergency surgery may anticipate emergency surgery.

Impact of surrounding tissue-type and peri-electrode gap in stereoelectroencephalography guided (SEEG) radiofrequency thermocoagulation (RF-TC): a computational study.

PURPOSE: To use computational modeling to provide a complete and logical description of the electrical and thermal behavior during stereoelectroencephalography-guided (SEEG) radiofrequency thermo-coagulation (RF-TC). METHODS: A coupled electrical-thermal model was used to obtain the temperature distributions in the tissue during RF-TC. The computer model was first validated by an ex vivo model based on liver fragments and later used to study the impact of three different factors on the coagulation zone size: 1) the difference in the tissue surrounding the electrode (gray/white matter), 2) the presence of a peri-electrode gap occupied by cerebrospinal fluid (CSF), and 3) the energy setting used (power-duration). RESULTS: The model built for the experimental validation was able to predict both the evolution of impedance and the short diameter of the coagulation zone (error < 0.01 mm) reasonably well but overestimated the long diameter by 2 - 3 mm. After adapting the model to clinical conditions, the simulation showed that: 1) Impedance roll-off limited the coagulation size but involved overheating (around 100 °C); 2) The type of tissue around the contacts (gray vs. white matter) had a moderate impact on the coagulation size (maximum difference 0.84 mm), and 3) the peri-electrode gap considerably altered the temperature distributions, avoided overheating, although the diameter of the coagulation zone was not very different from the no-gap case (<0.2 mm). CONCLUSIONS: This study showed that computer modeling, especially subject- and scenario-specific modeling, can be used to estimate in advance the electrical and thermal performance of the RF-TC in brain tissue.

Trans-Spinal Direct Current Stimulation in Neurological Disorders: A systematic review.

BACKGROUND AND PURPOSE: Trans-spinal direct current stimulation (tsDCS) is a noninvasive stimulation technique that applies direct current stimulation over spinal levels. However, the effectiveness and feasibility of this stimulation are still unclear. This systematic review summarizes the effectiveness of tsDCS in clinical and neurophysiological outcomes in neurological patients, as well as its feasibility and safety. METHODS: The search was conducted using the following databases: PEDro, Scopus, Web of Science, CINAHL, SPORTDiscus, and PubMed. The inclusion criteria were: Participants : people with central nervous system diseases; Interventions : tsDCS alone or in combination with locomotion training; Comparators : sham tsDCS, transcranial direct current stimulation, or locomotion training; Outcomes : clinical and neurophysiological measures; and Studies : randomized clinical trials. RESULTS: Eight studies with a total of 143 subjects were included. Anodal tsDCS led to a reduction in hypertonia, neuropathic pain intensity, and balance deficits in people with hereditary spastic paraplegia, multiple sclerosis, and primary orthostatic tremor, respectively. In contrast, cathodal tsDCS only had positive effects on balance and tremor in people with primary orthostatic tremor. No severe adverse effects were reported during and after anodal or cathodal tsDCS. DISCUSSION AND CONCLUSIONS: Although certain studies have found an effect of anodal tsDCS on specific clinical outcomes in people with central nervous system diseases, its effectiveness cannot be established since these findings have not been replicated and the results were heterogeneous. This stimulation was feasible and safe to apply. Further studies are needed to replicate the obtained results of tsDCS when applied in populations with neurological diseases.

Rotator Interval vs Posterior Approach Ultrasound-guided Corticosteroid Injections in Primary Frozen Shoulder: A Meta-analysis of Randomized Controlled Trials.

OBJECTIVE: To compare the efficacy of rotator interval (RI) vs posterior approach (PA) ultrasound (US) guided corticosteroid injections into the glenohumeral (GH) joint in primary frozen shoulder (PFS). DATA SOURCES: A systematic literature search for all relevant studies on Medline, Scopus, Embase, Web of Science, and Cochrane Central, up to January 2023 was conducted. STUDY SELECTION: Randomized controlled trials that directly compared the US-guided corticosteroid injection into the RI and GH joint using PA in patients clinically and radiographically diagnosed with PFS. DATA EXTRACTION: The primary outcome was pain, and the secondary outcomes were function, and range of motion (ROM). Two authors independently assessed the risk of bias using the Cochrane risk-of-bias tool version 2. A random-effects model and generic inverse variance method were performed. Effect sizes were estimated using mean difference (MD) and standardized mean difference (SMD). DATA SYNTHESIS: A total of 5 clinical trials involving 323 subjects were included for the meta-analysis. US-guided corticosteroid injections into the RI revealed significant pain relief (MD 1.33 [95% confidence interval (CI) 0.20 to 2.46]; P=.02) and significant functional improvement (SMD 1.31 [95% CI 0.11 to 2.51]; P=.03) compared with the PA after 12 weeks. CONCLUSION: The results suggest the injection of corticosteroid into RI space is more effective than PA after 12 weeks in improving both pain and functional scores in patients with PFS.

Efficacy and safety of sagittal synostosis surgery in older (> 12 months) patients: a systematic review and meta-analysis.

PURPOSE: Sagittal synostosis is the most common isolated craniosynostosis. Surgical treatment of this synostosis has been extensively described in the global literature, with promising outcomes when it is performed in the first 12 months of life. However, in some cases, patients older than 12 months arrive at the craniofacial center with this synostosis. A comprehensive study on efficacy and perioperative outcomes has yet to be fully explored in this population. This systematic review and meta-analysis aimed to assess the available evidence of surgical outcomes for the treatment of sagittal synostosis among older patients to analyze the efficacy and safety of synostosis surgery in this unique population. METHODS: PubMed, Embase, and Scopus were searched for studies published from inception to March 2024 reporting surgical outcomes of synostosis surgery in older patients (> 12 months) with isolated sagittal synostosis. The main outcome was the reoperation rate, with secondary endpoints including transfusion rates, aesthetic outcomes, and surgical complications. RESULTS: Nine studies were included in the final analysis. The pooled proportion of the reoperation rate was 1%. The rate of excellent aesthetic results was 95%. The need for transfusion associated with the procedures was 86%, and finally, surgical complications attained a pooled ratio of 2%, indicating minimal morbidity associated with the surgical repair. CONCLUSION: Sagittal synostosis surgery is a safe and effective procedure to perform in older patients; this meta-analysis suggests that open surgery confers a significant rate of excellent aesthetic results with a low reoperation rate and minimal complications associated with the intervention. Future research with direct comparisons among different techniques will validate the findings of this study, which will all contribute to the rigor of synostosis management.

Gear Classification in Skating Cross-Country Skiing Using Inertial Sensors and Deep Learning.

The aim of this current work is to identify three different gears of cross-country skiing utilizing embedded inertial measurement units and a suitable deep learning model. The cross-country style studied was the skating style during the uphill, which involved three different gears: symmetric gear pushing with poles on both sides (G3) and two asymmetric gears pushing with poles on the right side (G2R) or to the left side (G2L). To monitor the technique, inertial measurement units (IMUs) were affixed to the skis, recording acceleration and Euler angle data during the uphill tests performed by two experienced skiers using the gears under study. The initiation and termination points of the tests were controlled via Bluetooth by a smartphone using a custom application developed with Android Studio. Data were collected on the smartphone and stored on the SD memory cards included in each IMU. Convolutional neural networks combined with long short-term memory were utilized to classify and extract spatio-temporal features. The performance of the model in cross-user evaluations demonstrated an overall accuracy of 90%, and it achieved an accuracy of 98% in the cross-scene evaluations for individual users. These results indicate a promising performance of the developed system in distinguishing between different ski gears within skating styles, providing a valuable tool to enhance ski training and analysis.

Multidimensional associations of physical performance, balance, wellness and daily activities with frailty in older adults with coexisting frailty and diabetes.

BACKGROUND: The coexistence of frailty and type 2 diabetes mellitus in the older population heightens the risk of adverse events. However, research on functional and wellness factors associated with frailty in this population is limited. PURPOSE: To investigate the associations of physical performance, functional dependency, physical activity, nutritional status, sleep, self-perceived health and depression with frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. DESIGN: Cross-sectional. METHODS: The study included 123 community-dwelling older adults (73.7 ± 6.0 years) with pre-frailty/frailty and type 2 diabetes mellitus. Physical performance (Short Physical Performance Battery), functional dependency (Barthel Index and Lawton & Brody), physical activity and inactivity (GeneActiv wrist-worn accelerometer), malnutrition risk (Mini Nutritional Assessment), sleep (Pittsburgh Sleep Quality Index), self-perceived health (EuroQoL 5-Dimension 3-Level) and depression (Yesavage 15-item-Geriatric-Depression-Scale) were evaluated through personal interviews. Principal component analysis (PCA) was performed to categorize the variables into components, and logistic regressions were used to propose the best-fitted model for each component. RESULTS: The PCA identified four components: (i) physical performance, with gait speed and leg mean velocity as the main variables associated with frailty; (ii) balance, showing significant associations with monopodal balance; (iii) daily activities, with moderate to vigorous physical activity and the Lawton and Brody score as the main variables associated with frailty within this component; and (iv) wellness factors, with nutritional status, self-perceived health and depression score as the primary variables associated with frailty. CONCLUSIONS: This research underscores the significance of physical function and daily activities as protective factors against frailty in community-dwelling older adults with coexisting frailty and type 2 diabetes mellitus. The health dimension contributes both protective and risk factors, emphasizing the need for comprehensive assessments in managing frailty in this population. REPORTING METHOD: The study adhered to the STROBE checklist. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.

Evaluation of a low-cost portable NIRS device for monitoring muscle ischemia.

The main objective of this study is to evaluate the low-cost, open-source HEGduino device as a tissue oximetry monitor to advance the research of somatic NIRS monitoring. Specifically, this study analyzes the use of this portable functional NIRS system for detecting the cessation of blood flow due to vascular occlusion in an upper limb. 19 healthy patients aged between 25 and 50 were recruited and monitored using HEGduino device. Participants underwent a vascular occlusion test on one forearm. Raw values collected by HEGduino as well as the processed variables derived from the measurements were registered. Additional variables to characterize the signal noise during the tests were also recorded. The results of the data distribution curves for all the subjects in the study accurately detected the physiological events associated with transient tissue ischemia. The statistical analysis of the recorded data showed that the difference between the baseline values recorded by the red led (RED) and its normalized minimum variable was always different from zero (p < 0.014). Furthermore, the difference between the normalized baseline values recorded by the infrared led (IR) and the corresponding normalized minimum value was also different from zero (p < 0.001). The R-squared coefficient of determination for the noise variables considered in this study on the normalized RED and IR values was 0.08 and 0.105, respectively. The study confirms the potential of HEGduino system to detect an interruption of the blood flow by means of variations in regional tissue oxygen saturation. This study demonstrates the potential of the HEGduino device as a monitoring alternative to advance the study of the applicability of NIRS in muscle tissue oximetry.