Wide Variability Research Articles

Comparison of different methods for categorizing the individual susceptibility to motion sickness – A carsickness study

In studies aimed at developing avoidance strategies to reduce motion sickness (kinetosis) in autonomous vehicles, failing to account for the wide variability in individual kinetosis susceptibility can lead to inaccuracies and disregard effective countermeasures. Three methods for assessing individual susceptibility to carsickness – two questionnaires focusing on kinetosis experiences and a kinetosis-provoking lab test – were compared with the development of kinetosis during real car driving tests. Questions about car-specific kinetosis-provoking situations (MS-C) exhibit stronger correlations with kinetosis in car experiments compared to the commonly used questions about kinetosis experiences across different types of transportation (MS-VD). While lab-based testing remains highly reliable, especially considering men's tendency to underestimate their carsickness susceptibility in questionnaires, MS-C provides a valuable compromise in terms of technical and time expenses. These findings can also be used to assist passengers of autonomous driving cars in accurately assessing their sensitivity and activating customized countermeasure functions.

In vitro toxicity assessment of bioavailable iron in coal varieties of Central India

Introduction Information on bioavailable Iron (BAI) content in respirable coal dust (RCD) is crucial to address occupational health and safety, especially in preventing coal workers’ pneumoconiosis (CWP). Materials and methods In the present study, we determined BAI concentrations in seventy-seven coal samples collected from ten coal mining regions of Central India. The cytotoxic potential of BAI-RCD was established invitro by using alveolar epithelial (A549) and macrophage (U937) cell lines. The oxidative/antioxidant status, inflammations, and genotoxicity attributed to BAI-RCD exposure were evaluated and correlated with CWP pathophysiology. Results The mean BAI concentrations in the coal samples (n = 77) range from (275 to 9065 mg kg-1) and showed wide variability. Both cell lines were exposed to low (275 mg kg-1), moderate (4650 mg kg-1), and high (9065 mg kg-1) BAI-RCD samples showed significant (p < 0.001) cytotoxicity in a dose-dependent manner (low < moderate < high) compared to the control. After BAI-RCD treatment, both cell lines showed a decrease in antioxidant stress measures (SOD, CAT, and GSH) and a significant (p < 0.001) increase in oxidative stress parameters (NADPH, MPO, LPO, and PC). Furthermore, these cell line models demonstrated a statistically significant (p < 0.001) dose-dependent increase in cytokines (TGF-β1, IL-1β, TNF-α, MCP-1, and IL-6 cytokines) and oxidative DNA damage marker (8-OH-dG). Conclusion Results indicated that the central India coals (even at low BAI content) may be accountable for inflammatory responses and cytotoxicity. Hence, BAI can be important characteristic to establish safety standards for coal dust exposure before active mining.

Modeling hydrogen markets: Energy system model development status and decarbonization scenario results

Hydrogen can be used as an energy carrier and chemical feedstock to reduce greenhouse gas emissions, especially in difficult-to-decarbonize markets such as medium- and heavy-duty vehicles, aviation and maritime, iron and steel, and the production of fuels and chemicals. Significant literature has been accumulated on engineering-based assessments of various hydrogen technologies, and real-world projects are validating technology performance at larger scales and for low-carbon supply chains. While energy system models continue to be updated to track this progress, many are currently limited in their representation of hydrogen, and as a group they tend to generate highly variable results under decarbonization constraints. The present work provides insights into the development status and decarbonization scenario results of 15 energy system models participating in study 37 of the Stanford Energy Modeling Forum (EMF37), focusing on the U.S. energy system. The models and scenario results vary widely in multiple respects: hydrogen technology representation, scope and type of hydrogen end-use markets, relative optimism of hydrogen technology input assumptions, and market uptake results reported for 2050 under various decarbonization assumptions. Most models report hydrogen market uptake increasing with decarbonization constraints, though some models report high carbon prices being required to achieve these increases and some find hydrogen does not compete well when assuming optimistic assumptions for all advanced decarbonization technologies. Across various scenarios, hydrogen market success tends to have an inverse relationship to success with direct air capture (DAC) and carbon capture and storage (CCS) technologies. While most model-scenario combinations predict modest hydrogen uptake by 2050 – <10 million metric tons (MMT) – aggregating the top 10 % of market uptake results across sectors suggests an upper range demand potential of 42–223 MMT. The high degree of variability across both modeling methods and market uptake results suggests that increased harmonization of both input assumptions and subsector competition scope would lead to more consistent results across energy system models. The wide variability in results indicates strongly divergent conclusions on the role of hydrogen in a decarbonized energy future.

Pharmacokinetics of Piperacillin-Tazobactam in Critically Ill Patients with Open Abdomen and Vacuum-Assisted Wound Closure: Dosing Considerations Using Monte Carlo Simulation.

Open abdomen with vacuum-assisted wound closure therapy (OA/VAC) is frequently used in critically ill patients although the impact of OA/VAC on antibiotics pharmacokinetics (PK) remains unknown. We thus aimed to characterize the PK of piperacillin-tazobactam (PTZ) in critically ill patients with OA/VAC and assess the optimal dosing regimens based on pharmacodynamics (PD) target attainment. Over a 15-month study period, 45 patients with OA/VAC treated with PTZ administered continuously and adapted to 24 h creatinine clearance (CLCR) underwent measurements of free concentrations in their plasma, urine, VAC exudate, and peritoneal fluid. Population PK modeling was performed considering the effect of covariates, and Monte Carlo simulations were employed to determine the probability of target attainment (PTA) for the PK/PD targets (100% fT > 16 mg/L) in the plasma and at the peritoneal site at steady state. Piperacillin concentrations were described using a two-compartment model, with age and total body weight as significant covariates for central volume of distribution (V1) and estimated renal function for clearance (CL). Tazobactam concentrations were described using a two-compartment model with estimated renal function as a significant covariate. The central volume of distributions V1 of piperacillin and tazobactam were 21.2 and 23.2 L, respectively. The VAC-induced peritoneal clearance was negligible compared to renal clearance. Most patients achieved the desirable PK/PD target when using a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day. Despite a wide inter-individual variability, the influence of OA/VAC on piperacillin and tazobactam PK parameters is not straightforward. The use of a CLCR-pondered PTZ dosing regimen from 12 g/1.5 g/day to 20 g/2.5 g/day is needed to reach a PTA > 85%.

Age-dependencies of the electroretinogram in healthy subjects.

The purpose of this study was to evaluate the age-dependency of amplitudes and implicit times in the electroretinograms (ERGs) of healthy individuals and provide clinicians and researchers with a reference for a variety of stimulus paradigms. Full-field electroretinography was conducted on 73 healthy participants aged 14-73 using an extended ISCEV standard protocol that included an additional 9Hz flicker stimulus for assessing rod function and special paradigms for isolated On-Off and S-cone responses. Correlation coefficients and best-fit regression models for each parameter's age-dependency were calculated. Dark-adapted ERGs, in particular, displayed notable age-related alterations. The attenuation and delay of the b-wave with higher age were most significant in the dark-adapted, rod-driven 0.001cds/m2 flash ERG. The age-dependent reduction of the a-wave amplitude was strongest in the standard dark-adapted 3cds/m2 flash condition. Cone-driven, light-adapted responses to either flash or flicker stimuli displayed comparatively small alterations at higher age. S-cone function tended to diminish at an early age, but the effect was not significant in the whole population. The results suggest that rod and cone function decline at different rates with age, with rods being generally more affected by aging. Nonetheless, response amplitudes displayed a wide variability across the whole sample.

CFTR complex alleles and phenotypic variability in cystic fibrosis disease.

Cystic fibrosis (CF) is inherited by CFTR (cystic fibrosis transmembrane conductance regulator) gene mutations. A variety of mutations have been identified in the CFTR gene that may be associated with cystic fibrosis, and these mutations demonstrate extensive molecular genetic heterogeneity in this disease. Little is known about the molecular mechanism by which mutations affect CFTR function, and only a minority of mutations have been characterized by functional studies. There has been an increase in the number of complex alleles. This may partly explain the difficulty in establishing genotype-phenotype correlations and complicate genetic counseling and diagnosis in some cases. Therefore, the identification of complex alleles has several important implications for recessive disorders. This will facilitate diagnosis; improve judgements concerning prognosis, and enable appropriate genetic counselling for affected families. This review describes the complex cystic fibrosis allele to better understand the contribution of this allele in the wide phenotypic variability of cystic fibrosis disease. It occurs in the complex allele that the second cis mutation can modulate the effects of the first mutation or vice versa. The phenotypic variability between CF or CFTR-RD (CFTR related disease) patients may be due to several factors, including different genetic and environmental backgrounds. It is important to determine the allele complex so that optimal treatment can be established.

Monitoring reaction time to digital device in the very-old to detect early cognitive decline

Early detection of cognitive decline is essential for timely intervention and effective management of age-related impairments. We monitored repetitive reaction times to a simple task on senior-friendly tablet computers among 72 functionally independent older adults, with a mean age of 82, ranging up to 100 years, within natural settings over two years. Functional principal component analyses revealed a consistent decrease in reaction time in line with their task experience among those without subjective cognitive decline. Conversely, individuals reporting subjective cognitive decline showed no consistent trend and exhibited wide variability over time. These distinctive reaction time trajectories in very old adults suggest the potential for monitoring as a non-invasive, convenient method for early detection of cognitive impairment.

ON THE DEVELOPMENT AND CURRENT STATE OF THE PRONUNCIATION NORM IN FRENCH LANGUAGE

This article is devoted to the development and current state of the French pronunciation norm. Learning a foreign language pronunciation in its standard variant is a difficult task not only due to the need to master new articulatory gestures, but also to understand what is normative in pronunciation. For the French language, which has more than 90 million native speakers, the issue is particularly acute. Since the establishment of French as a state language, the choice of pronunciation standard was based on the pronunciation of certain social groups (royal nobility, educated classes, radio presenters) and geographical boundaries (Paris, Ile-de-France region, major cities of France). The codification of the French pronunciation norm has evolved from strictly prescriptive to reflecting the maximum possible variants. The recent decades researches reveal a lack of uniformity in the pronunciation of native speakers, even within a homogeneous group. The modern pronunciation norm indicates the absence of a single rigid pattern and its wide regional variability.

Chromosome 16p11.2 microdeletion syndrome with microcephaly and Dandy-Walker malformation spectrum: expanding the known phenotype

BackgroundChromosome 16p11.2 deletions and duplications were found to be the second most common copy number variation (CNV) reported in cases with clinical presentation suggestive of chromosomal syndromes. Chromosome 16p11.2 deletion syndrome shows remarkable phenotypic heterogeneity with a wide variability of presentation extending from normal development and cognition to severe phenotypes. The clinical spectrum ranges from neurocognitive and global developmental delay (GDD), intellectual disability, and language defects (dysarthria /apraxia) to neuropsychiatric and autism spectrum disorders. Other presentations include dysmorphic features, congenital malformations, insulin resistance, and a tendency for obesity. Our study aims to narrow the gap of knowledge in Saudi Arabia and the Middle Eastern and Northern African (MENA) region about genetic disorders, particularly CNV-associated disorders. Despite their rarity, genetic studies in the MENA region revealed high potential with remarkable genetic and phenotypic novelty.ResultsWe identified a heterozygous de novo recurrent proximal chromosome 16p11.2 microdeletion by microarray (arr[GRCh38]16p11.2(29555974_30166595)x1) [(arr[GRCh37]16p11.2(29567295_30177916)x1)] and confirmed by whole exome sequencing (arr[GRCh37]16p11.2(29635211_30199850)x1). We report a Saudi girl with severe motor and cognitive disability, myoclonic epilepsy, deafness, and visual impairment carrying the above-described deletion. Our study broadens the known phenotypic spectrum associated with recurrent proximal 16p11.2 microdeletion syndrome to include developmental dysplasia of the hip, optic atrophy, and a flat retina. Notably, the patient exhibited a rare combination of microcephaly, features consistent with the Dandy-Walker spectrum, and a thin corpus callosum (TCC), which are extremely infrequent presentations in patients with the 16p11.2 microdeletion. Additionally, the patient displayed areas of skin and hair hypopigmentation, attributed to a homozygous hypomorphic allele in the TYR gene.ConclusionThis report expands on the clinical phenotype associated with proximal 16p11.2 microdeletion syndrome, highlighting the potential of genetic research in Saudi Arabia and the MENA region. It underscores the importance of similar future studies.

Sex-based utilization and outcomes of cold-stored whole blood for trauma resuscitation: Analysis of a prospective multicenter study.

Resuscitation with cold-stored whole blood (WB) has outcome benefits, but benefits varied by patient sex is unknown. There are also concerns about alloimmunization risk for premenopausal females given WB, leading to some protocols excluding this cohort. We sought to analyze WB utilization, outcomes, and disparities by patient sex. This is a secondary analysis of a prospective multicenter study of WB resuscitation. Patients were stratified by sex and compared by transfusion strategy of WB or component therapy (CT). Generalized estimated equation models using inverse probability of treatment weighting were utilized. There were 1,617 patients (83% male; 17% female) included. Females were less likely to receive WB versus males (55% vs. 76%; p < 0.001), with wide variability between individual centers (0%-33% female vs. 66%-100% male, p < 0.01). Male WB had more blunt trauma (45% vs. 31%) and higher shock index (1.0 vs. 0.8) compared with the male CT cohort (all p < 0.05) but similar Injury Severity Score. The female WB cohort was older (53 vs. 36) and primarily blunt trauma (77% vs. 62%) compared with the female CT cohort (all p < 0.05) but had similar shock index and Injury Severity Score. Male WB had lower early and overall mortality (27% vs. 42%), but a higher rate of acute kidney injury (16% vs. 6%) vs. the male CT cohort (all p < 0.01). Female cohorts had no difference in mortality, but the WB cohort had higher bleeding complications. Whole blood use was independently associated with decreased mortality (OR, 0.6; p < 0.01) for males but not for females (OR, 0.9; p = 0.78). Whole blood was independently associated with a decreased mortality for males with no difference identified for females. Whole blood was significantly less utilized in females and showed wide variability between centers. Further study of the impact of patient sex on outcomes with WB and WB utilization is needed. Prognostic/Epidemiological; Level IV.

Analysis of Recent Sleep Surgery Fellowship Training.

Since 2011, otolaryngologists aiming to become certified in sleep medicine have had to complete an ACGME accredited sleep medicine fellowship. In addition to standard sleep medicine and sleep surgery fellowships, several institutions have developed hybrid ACGME sleep medicine programs that incorporate sleep surgery training. Our primary aims were to understand the balance between sleep medicine and surgical training requirements and the surgical volume of recent graduates across the three pathways. Our secondary aim was to assess their employment post-graduation. An improved understanding of the current state of sleep surgeon training could better inform both applicants and programs and be used to guide fellowship curriculum development. Between 2017 and 2023, we identified 26 surgeons who completed a sleep focused fellowship. An anonymous survey was developed and emailed to them. The survey assessed clinic and operating balance, procedures completed during fellowship, and comfort with these procedures as attendings. Finally, the survey assessed the job prospects of graduates. Data were analyzed with Prism 10. There were 19 respondents with 52.6% completing a hybrid fellowship, 21.3% completing a sleep medicine fellowship, and 31.6% completing a sleep surgery fellowship. Approximately 84.8% completed ACGME accredited otolaryngology training prior to fellowship. The three most common surgeries were hypoglossal nerve stimulators, pharyngoplasty, and nasal surgeries. Respondents on average received 2.4 job offers, 55% returned to their residency institution, and 89.5% were in academics. Our survey demonstrates a wide variability in sleep-focused fellowships for surgeons, but the employment market for these trainees is robust. N/A Laryngoscope, 2024.

DNA contamination within recombinant adeno-associated virus preparations correlates with decreased CD34+ cell clonogenic potential

Recombinant adeno-associated viruses (rAAV) are promising for applications in many genome editing techniques through their effectiveness as carriers of DNA homologous donors into primary hematopoietic stem and progenitor cells (HSPC) but have many outstanding concerns. Specifically, their biomanufacturing and the variety of factors that influence the quality and consistency of rAAV preps are in question. During the process of rAAV packaging, a cell line is transfected with several DNA plasmids that collectively encode all the necessary information to allow for viral packaging. Ideally, this process results in packaging of complete viral particles only containing rAAV genomes; however, this is not the case. Through this study, we were able to leverage Single-Stranded Virus (SSV)-seq, an NGS-based method to quantify all DNA species present within rAAV preps. From this, it was determined that much of the DNA within some rAAV preps is not vector-genome derived, and there is wide variability in the contamination by DNA across various preps. Furthermore, we demonstrate that transducing CD34+ hematopoietic stem and progenitor cells (HSPC) with preps with higher contaminating DNA resulted in decreased clonogenic potential, altered transcriptomic profiles, and decreased genomic editing. Collectively, this study characterized the effects of DNA contamination within rAAV preps on CD34+ HSPC cellular potential.

ESTIMATION OF GENETIC VARIABILITY, HERITABILITY, AND GENETIC ADVANCE FOR YIELD AND YIELD CONTRIBUTING CHARACTERS IN SORGHUM (SORGHUM BICOLOR L.)

The field experiment was conducted at the Experimental Farm of College of Agriculture, Latur, during Kharif – 2021–2022 with 26 genotypes of Sorghum, including three checks genotypes as PVK-1009-C, PVK-400-C, and PVK-809-C, with the goal of studying genetic variability, heritability, and genetic advance for yield and yield contributing characters in Sorghum (Sorghum bicolor L.). An analysis of variance involving 26 Sorghum genotypes for 12 quantitative characters revealed significant differences for all the traits under study indicating the presence of wide genetic variability in the experimental materials. Fodder yield per plant field grade score, plant height, grain yield per plant, threshed grade score, and test weight had a significantly high genotypic coefficient of variation (GCV) and phenotypic coefficient of variation magnitudes. The present investigation clarified that plant height, number of grains per primary, field grade score, threshed grade score, grain yield per plant, and fodder yield per plant these character have high heritability coupled with a high genetic advance and high GCV, indicating the role of additive genes in governing the inheritance of these traits, which could be improved through simple selection.

Beyond the surface: a closer look at the stratigraphy of synthetic-coated fabrics in fashion collections and commercial samples through optical microscopy

Synthetic-coated fabrics, often made of short-life expectancy coatings, namely plasticised poly(vinyl chloride) (p‑PVC) and thermoplastic polyurethane (TPU), are challenging to preserve. These materials are poorly studied within the conservation field, and there is a lack of research and solutions for their preservation. This study aimed to provide insight into the yet unknown variability of p-PVC and TPU-coated fabrics in fashion collections. The subtle differences in layer construction and morphology were investigated in a selected set of materials to unveil production methods and better understand delamination damages, namely peeling and flaking. Optical microscopy provided primary material assessment, complemented by ATR-FTIR for molecular identification. A wide variability of synthetic-coated fabrics was reported and connections between morphology, production methods and delamination damages were suggested. Optical microscopy proved to be a powerful tool in the study of the stratigraphy of coated fabrics, enhancing material knowledge for more informed conservation decisions.

Beyond the surface: a closer look at the stratigraphy of synthetic-coated fabrics in fashion collections and commercial samples through optical microscopy

Synthetic-coated fabrics, often made of short-life expectancy coatings, namely plasticised poly(vinyl chloride) (p‑PVC) and thermoplastic polyurethane (TPU), are challenging to preserve. These materials are poorly studied within the conservation field, and there is a lack of research and solutions for their preservation. This study aimed to provide insight into the yet unknown variability of p-PVC and TPU-coated fabrics in fashion collections. The subtle differences in layer construction and morphology were investigated in a selected set of materials to unveil production methods and better understand delamination damages, namely peeling and flaking. Optical microscopy provided primary material assessment, complemented by ATR-FTIR for molecular identification. A wide variability of synthetic-coated fabrics was reported and connections between morphology, production methods and delamination damages were suggested. Optical microscopy proved to be a powerful tool in the study of the stratigraphy of coated fabrics, enhancing material knowledge for more informed conservation decisions.

Phenotype and genotype features of isolated cystic kidney diseases with autosomal recessive type of inheritance in children

The relevance of the problem of hereditary cystic kidney diseases (cystosis) is due to the wide variability of the renal phenotype and the genotype that determines the prognosis, the progression to renal failure as early as in childhood. Purpose. To present the results of the analysis of the correlation of genotype and phenotype, renal function in isolated cystic kidney diseases with an autosomal recessive type of inheritance in children. Material and methods. in 14 children (from 13 families) aged 9 months — 17 years, the features of the clinical phenotype of kidney cysts with autosomal recessive type of inheritance and gene mutation were evaluated according to the results of a molecular genetic study. Results. In 3 (23 %) of 13 families, the family history is burdened by kidney cysts. The characteristic of gene mutation in cystic kidney diseases with autosomal recessive type of inheritance in 13 patients is presented (in 2 tables). Of the 21 identified variants in the genes PKHD1, INVS, NPHP1, TMEM67, 15 (71 %) had known pathogenic significance, 6 (29 %) had previously undescribed variants in data-bases. Variants of the PKHD1 gene were identified in 11 children with the phenotype of polycystic kidney disease with autosomal recessive type of inheritance and liver fibrosis. In the study, variant C.107C&gt;T (Thr36Met) is the most common among children with identified variants of the PKHD1 gene in autosomal recessive polycystic kidney disease in 5 out of 21 (23.8 %), c.664A&gt;G (Ile222Val) in 1 (4.8 %), c.6992T&gt;A (Ile2331Lys) in 1 (4.8 %), c.10444C&gt;T (Arg3482Cys) at 1 (4.8 %). Infantile (n=1) and juvenile (n = 2) nephronophthysis were confirmed in 3 children with homozygous and compound heterozygous pathogenic variants in the INVS, NPHP1, TMEM67 genes. Conclusion. The features of the genotype and phenotype are presented in 14 children with autosomal recessive type of inheritance of isolated kidney cysts in autosomal recessive polycystic kidney disease (n = 11) and nephronophthysis (n = 3), of whom chronic kidney disease was established in 13 children aged 2–17 years: in 4 (30.8 %) C1, in 4 (30.8 %) C2, in 3 (23 %) C3, in 1 (7.7 %) C4, in 1 (7.7 %) C5.

Preventing Recurrence of Crohn's Disease Post-Ileocaecal Surgery in Paediatric Patients: A Therapy Guide Based on Systematic Review of the Evidence.

Ileocaecal resection (ICR) is frequent in paediatric patients with Crohn's disease (pCD). Despite rates of reoperation being low, the risk of clinical or endoscopic post-operative recurrence (POR) is high; effective medical strategies to prevent POR are thus needed. The aim of this systematic review(SR) was to identify and evaluate the published literature on post-operative medical prevention of POR in pCD to draft a possible therapy guide for pCD patients undergoing ICR. We performed an SR according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standards and registered it in the PROSPERO database (ID: CRD42024533855). The population, intervention, control, outcome (PICO) model was focussed on post-surgical medical prevention of POR in pCD with clearly expressed definition of recurrence (endoscopically using a standardized scoring system (e.g. Rutgeerts score) or by laboratory markers, for example, faecal calprotectin (F-CPT), C-reactive protein (CRP) or by histological findings or by clinical activity indexes [e.g. weighted paediatric Crohn's disease activity index - (w)PCDAI]. From inception until 29 February 2024, the following databases were searched: PubMed/MEDLINE, Scopus/Embase, Web of Sciences, Evidence-Based Medicine Reviews (including Cochrane), Cochrane Central Registrar of controlled Trials (CENTRAL), ClinicalTrials.gov and EudraCT. Retrieved articles were evaluated for eligibility and finally selected publications for risk of bias using ROBINS-I tool. Out of 811 publications identified by the search, only 5 fulfilled inclusion criteria of the SR. None of the studies fully answered our PICO question. The studies were overall of poor quality and the heterogeneity of the data did not allow us to perform meta-analysis, detailed statistical analysis or formal synthesis of data. Adverse events of post-operative medication were not described in any of the included studies. Existing guidelines of European Society for Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN), North American Society for Paediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN), European Crohn's and Colitis Organisation (ECCO) and American Gastroenterological Association (AGA) were reviewed and paediatric therapy guide for pCD undergoing ICR was drafted with respect to recent SRs and meta-analyses in adult population and including scarce paediatric data identified by our SR. As pCD patientsundergoing ICR are a high-risk population, they should not be left untreated post-operatively. Anti-tumour necrosis factor (anti-TNF) drugs should be considered as first-line therapy in the majority of patients. Non-anti-TNF biologics should be considered in case of anti-TNF failure. Regular endoscopic monitoring starting at 6 months after the surgery and supported by regular F-CPT evaluation should be used to identify early endoscopic recurrence and to escalate the treatment. Our SR revealed that there is wide variability in treatment strategies in children, and high-quality data are generally lacking. At the moment, paediatric prophylaxis of POR should be guided by available adult evidence with respect to the high-risk nature of pCD. Extensive research in pCD should be encouraged.

Conventional High-Dose vs Low-Dose Hyaluronidase for Skin Necrosis after Hyaluronic Acid Fillers: A Systematic Review and Pilot Meta-Analysis.

Hyaluronidase remains the mainstay treatment for skin necrosis due to vascular occlusion after hyaluronic acid (HA) dermal fillers. There is wide variability in protocols for the administration of hyaluronidase. Most protocols, however, lack strong evidence regarding hyaluronidase dosages. We conducted a systematic review and pilot meta-analysis, searching four international databases from inception until December 2023 for clinical studies reporting on two or more patients receiving hyaluronidase for skin necrosis after hyaluronic acid fillers. Random-effects (DerSimonian and Laird) meta-analyses were conducted. The primary outcome was the pooled proportion of complete scar resolution. We rated intra-study risk of bias using the Joanna Briggs Institute checklists and assessed the certainty of evidence using the GRADE approach. We included 15 studies totaling 223 patients. The pooled proportion of complete scar resolution after hyaluronidase administration was 77.8% (95%-CI: 65.5% to 86.6%, pegger = 0.093, low certainty). Patients treated with high doses of hyaluronidase (>500 international units [IUs]) had lower rates of resolution of 69.6% (95%-CI: 41.2% to 88.3%) compared to those treated with low doses (500IU or less) that had 88.1% rate of resolution (95%-CI: 86.0% to 96.2%), though not statistically significant (p= 0.18). The use of adjunct therapies did not have a statistically significant effect on outcomes. A higher proportion of patients receiving low doses (500IU or less) (88.1%) had complete scar resolution compared to patients receiving high doses (69.7%), though not statistically significant (p=0.18). Future studies should provide more granular details on their protocols to benefit the formulation of evidence-based guidelines in future. This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 . CRD42024538661.

Consolidating two-dimensional liquid chromatography–high-resolution tandem mass spectrometry (LC×LC-HRMS/MS) technique for the non-targeted analysis of poly- and perfluorinated substances: A trial on aqueous film-forming foams

To date, poly- and perfluoroalkyl substances (PFAS) represent a real threat for their environmental persistence, wide physicochemical variability, and their potential toxicity. Thus far a large portion of these chemicals remain structurally unknown. These chemicals, therefore, require the implementation of complex non-targeted analysis workflows using liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) for their comprehensive detection and monitoring. This approach, even though comprehensive, does not always provide the much-needed analytical resolution for the analysis of complex PFAS mixtures such as fire-fighting aqueous film-forming foams (AFFFs). This study consolidates the advantages of the LC×LC technique hyphenated with high-resolution tandem mass spectrometry (HRMS/MS) for the identification of PFAS in AFFF mixtures. A total of 57 PFAS homolog series (HS) were identified in 3M and Orchidee AFFF mixtures thanks to the (i) high chromatographic peak capacity (n’2D,c ~ 300) and the (i) increased mass domain resolution provided by the “remainder of Kendrick Mass” (RKM) analysis on the HRMS data. Then, we attempted to annotate the PFAS of each HS by exploiting the available reference standards and the FluoroMatch workflow in combination with the RKM defect by different fluorine repeating units, such as CF2, CF2O, and C2F4O. This approach resulted in 12 identified PFAS HS, including compounds belonging to the HS of perfluoroalkyl carboxylic acids (PFACAs), perfluoroalkyl sulfonic acids (PFASAs), (N-pentafluoro(5)sulfide)-perfluoroalkane sulfonates (SF5-PFASAs), N-sulfopropyldimethylammoniopropyl perfluoroalkane sulfonamides (N-SPAmP-FASA), and N-carboxymethyldimethylammoniopropyl perfluoroalkane sulfonamide (N-CMAmP-FASA). The annotated categories of perfluoroalkyl aldehydes and chlorinated PFASAs represent the first record of PFAS HS in the investigated AFFF samples.

Prognostic factors for tube feeding in type I SMA patients treated with disease-modifying therapies: a cohort study

The aim of this study was to assess the need for tube feeding in a cohort of treated infants with type I SMA and to identify predictive factors. All patients were classified at baseline, when treatment started, and at follow-up according to their functional level and the need for tube feeding. Fisher’s exact test was used to examine the associations between the outcome at the last follow-up and SMA type, SMN2 copy number, and baseline nutritional status. ANOVA was performed to compare CHOP INTEND scores and age at treatment initiation with outcomes. The cohort includes 75 type I SMA infants treated between 0.1 and 5 years of age. At the last follow-up, 34 had no need for tube feeding, 9 had tube feeding but were also able to be fed by mouth, and 32 had tube feeding and were unable to be fed by mouth. Thirty of the 41 infants with tube feeding at follow-up already had feeding difficulties when treatment was started. The need for tube feeding at follow-up was associated with the level of feeding involvement at baseline and with CHOP INTEND scores [p < 0.001] but not with SMN2 copy number, SMA type 1 subtypes or age at treatment. The results of this study suggest that the need for tube feeding is not frequent in treated infants with type I SMA and, when occurring, can be predicted by the level of feeding involvement and low CHOP INTEND scores at baseline.What is Known:• The advent of disease-modifying therapies is increasingly changing the approach to swallowing and nutritional management in type I SMA.• Clinical trials and real-world data using all three disease-modifying therapies report a rather wide variability of feeding outcome and need for tube feeding that is often related to different cohorts that makes comparison between studies very difficult.What is New:• The real-world findings of this study, including all the children treated since treatments became available, confirmed that the need for tube feeding is not an invariable finding.• The level of feeding involvement at baseline appears to be a reliable prognostic indicator of bulbar outcome.• The results highlight the need for interventional studies with structured Speech and Language Therapist protocols that will help to better understand the extent to which bulbar function can be maintained or regained even in children requiring tube feeding.