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Anatomical 3D-printed nasal casts are valuable models to investigate intranasal drug deposition, providing preclinical data that cannot be obtained in animal models. However, these models are limited since they are often derived from a single patient or represent a mean of several groups. The present study aimed to better characterize the anatomical differences of the nasal cavity in a European sub-population and to assess the potential impact of anatomical variations on intranasal deposition by medical devices. Ninety-eight cranial computed tomography scans of patients were selected and analyzed in 2D and 3D conformations. They showed symmetry of cavities and a high level of heterogeneity of measurements, especially volume and area, in the population. Three anatomical groups with distinct nasal geometry were identified and 3D nasal casts of the most representative patient of each group were printed. Fluorescein was administered using three medical devices: a nasal spray, a sonic jet nebulizer and a prototype mesh-nebulizer. The deposition profiles were compared with the Aeronose® as a reference. Our results show that anatomical variations influenced the deposition profiles depending on the device, with a higher variation with spray and the mesh-nebulizer. This work emphasises the importance of anatomical parameters on drug intranasal deposition and the need to evaluate inhaled drugs on different 3D nasal casts reflecting the target population., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: HERVE VIRGINIE reports financial support was provided by Research Center for Respiratory Diseases − Inserm U1100. LE GUELLEC SANDRINE reports a relationship with DTF medical that includes: employment. In the past 3 years, NHV and her group received research supports and subcontracting fees from medical device companies, including Aerogen and DTF medical outside the scope of the present study and from Aptar Pharma and Nemera on the development of nasal models. The Aeronose® model belong to equally to APTAR PHARMA/University of Tours – CEPR Inserm U1100/DTFmedical. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

Dalbavancin is a relatively new long-acting anti-Gram positive antimicrobial approved for the treatment of acute bacterial skin and skin structures infections. An increasing number of observational studies and case series were published on its off-label uses. Great interest is emerging about complicated cases where antibiotic treatment cannot be discontinued, and a chronic suppressive therapy is needed. We described a case series of 6 patients treated or ongoing on treatment with dalbavancin as chronic suppressive therapy (CAST) administered with the following regimen: dalbavancin 1500 mg on day 1 and 8 and then every 4 weeks. CAST median duration was 27 weeks. Five out of 6 patients reached a good clinical control of the infection (one of them completely resolved) while in one case we observed a recurrence of the infection. No adverse events were detected. Larger studies are needed to better clarify dalbavancin off-label uses and the most appropriate dose regimen.

Background: The long-term outcomes (≥ 2 years of follow-up) of volar locked plate (VLP) fixation versus closed reduction and casting (CRC) for the treatment of displaced distal radial fractures (DRFs) remain unclear. This study aimed to conduct a meta-analysis comparing the long-term clinical outcomes of VLP and CRC in elderly patients (aged ≥ 60 years)., Methods: A comprehensive search of PubMed, Web of Science, and Cochrane Library was performed to identify studies comparing the long-term outcomes of VLP and CRC for DRFs. Only randomized controlled trials (RCTs) with a mean follow-up duration of at least 2 years and participants aged 60 years or older were included. The risk of bias in the included studies was assessed. The primary outcome measure was the Patient-Rated Wrist Evaluation (PRWE). Secondary outcomes included the Disabilities of the Arm, Shoulder, and Hand (DASH) questionnaire, EuroQol 5 Dimension 5-level score (EQ-5D-5 L), grip strength, and incidence of reoperation., Results: Four RCTs, comprising 423 patients, were included. The meta-analysis revealed that VLP fixation was associated with significantly improved outcomes compared to CRC in terms of PRWE score (pooled mean difference: -6.21; 95% CI: -10.28 to -2.15; p = 0.003), DASH score (pooled mean difference: -8.18; 95% CI: -13.35 to -3.01; p = 0.002), and grip strength (pooled mean difference: -6.63; 95% CI: 0.25 to 13.01; p = 0.04). There were no significant differences in EQ-5D-5 L score (95% CI: -0.08 to 0.05; p = 0.74) or incidence of reoperation (RR = 0.56; 95% CI: 0.22 to 1.42; p = 0.22)., Conclusions: A two-year follow-up of displaced DRFs in elderly patients showed no significant long-term clinical advantage of VLP fixation over CRC., Competing Interests: Declarations. Ethical approval: Not applicable. Consent for publication: All authors have stated for their consent for publication. CRD: 42024532685. Final statements: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)

Ultrafine particles (UFP) are the smallest atmospheric particulate matter linked to air pollution-related diseases. The extent to which UFP's physical and chemical properties contribute to its toxicity remains unclear. It is hypothesized that UFP act as carriers for chemicals that drive biological responses. This study explores robust methods for generating reference UFP to understand these mechanisms and perform toxicological tests. Two types of combustion-related UFP with similar elemental carbon cores and physical properties but different organic loads were generated and characterized. Human alveolar epithelial cells were exposed to these UFP at the air-liquid interface, and several toxicological endpoints were measured. UFP were generated using a miniCAST under fuel-rich conditions and immediately diluted to minimize agglomeration. A catalytic stripper and charcoal denuder removed volatile gases and semi-volatile particles from the surface. By adjusting the temperature of the catalytic stripper, UFP with high and low organic content was produced. These reference particles exhibited fractal structures with high reproducibility and stability over a year, maintaining similar mass and number concentrations (100 μg/m 3 , 2.0·10 5 #/cm 3 ) and a mean particle diameter of about 40 nm. High organic content UFP had significant PAH levels, with benzo[a]pyrene at 0.2 % (m/m). Toxicological evaluations revealed that both UFP types similarly affected cytotoxicity and cell viability, regardless of organic load. Higher xenobiotic metabolism was noted for PAH-rich UFP, while reactive oxidation markers increased when semi-volatiles were stripped off. Both UFP types caused DNA strand breaks, but only the high organic content UFP induced DNA oxidation. This methodology allows modification of UFP's chemical properties while maintaining comparable physical properties, linking these variations to biological responses., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There is an increasing demand for the treatment of problematic cannabis use (PCU) in low-income and middle-income countries. Jamaica's historical inclination towards cannabis use underscores the need for research in addressing this issue., Objectives: To determine the prevalence and patterns of cannabis use and assess the sociodemographic factors, psychosocial correlates, knowledge and perceptions associated with severe PCU among Jamaicans using nationally representative data., Methods: This study involved a secondary data analysis of the last Jamaica National Drug Prevalence Survey. It included 786 participants who used cannabis in the past year and completed the Cannabis Abuse Screening Test (CAST). The CAST has been validated against the Diagnostic and Statistical Manual of Mental Disorders (DSM), with a score ≥ 7 meeting the criteria for severe PCU. CAST scores were dichotomized utilizing these thresholds, and data generated were analyzed with SPSS version 25 using Pearson's χ2 test and logistic regression., Results: In the past year, 53.3% of Jamaicans who smoked cannabis had a score of 7 or higher on the CAST and smoked an average of 62.21 joints per month. Male respondents were twice as likely to have severe PCU as females. Additionally, young, middle, and older adults were respectively 3, 5 and 3 times more likely to report severe PCU compared to adolescent respondents. Participants who started cannabis use at 11 years and under, 12-17 years, and 18-25 years were respectively 5, 7 and 7 times more likely to report severe PCU than those at 26 years and older. Moreover, easy access to cannabis, a high perceived need for treatment, belief in increased national drug use prevalence, and awareness of the National Drug Control and Prevention Agency were associated with increased odds of reporting severe PCU., Conclusion: One out of every two Jamaicans who used cannabis in the past year reported severe PCU and smoked an average of two cannabis joints per day. Early initiation increases the risk of severe PCU. Accordingly, a public health approach involving multiple sectors is needed to provide treatment options., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Lalwani, De La Haye, Kerr, Abel and Sewell.)

There are lots of gene editing tools for targeting genome sequences. Some are almost known, and most are a complete mystery and undiscovered. CRISPR/Cas editing tools have brought about a major revolution in medicine. Researchers have shown that CRISPR can modify DNA much more accurately, economically and easily than previous methods. CRISPR has proven itself effective for the deletion, replacement and insertion of DNA fragments into cell types, tissues and organisms. Recently, combining CRISPR/Cas with factors (transcription factors/repressors, exonucleases, endonucleases, transposons, caspase, fluorescent proteins, oxidoreductive enzymes, DNA/RNA polymerases), and elements (aptamers, barcodes, fluorescent probes, Trigger) have provided genome, transcriptome, proteome and epigenome modification. These modules are being investigated for cancer prevention and therapy and this review focuses on such innovative combinations that hopefully will become a clinical reality in the near future., Competing Interests: Declaration of competing interest This paper has been read and approved by all the authors and all of them declared no conflicts of interest., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Previously, we reported excellent results with the combination of post-transplant cyclophosphamide (PTCy), abatacept, and a short course of tacrolimus (CAST) for the prevention of graft-versus-host disease (GvHD) following peripheral blood haploidentical transplantation. To further substantiate these results, we performed a propensity score-matched analysis. Patients enrolled in the CAST trial were matched with patients from a contemporaneous cohort from the Center for International Blood and Marrow Transplant Research database who received PTCy, tacrolimus, and mycophenolate mofetil, using nearest neighbor propensity score matching. An excellent balance between pairs was achieved as measured by the density distribution and standardized differences of covariates (median 0.09). The rates of acute GvHD grades II to IV at day +120 and 1-year GvHD- and relapse-free survival were 16.7% and 66.7% in the CAST cohort versus 28.6% and 47.6% in the control group, respectively. This trend did not reach statistical significance (P = .14 and .07), possibly due to the small numbers of patients and events. On the other hand, CAST was associated with a statistically significant reduction in the incidence of relapse (9.5% versus 26.2%, P = .045) with improved disease-free survival (85.7% versus 61.9%, P = .01). Our data provides a strong impetus to examine CAST in a randomized clinical trial., (Copyright © 2024 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.)

Earthworms are pivotal in soil ecosystems due to their crucial role in shaping soil characteristics through casts and burrow walls. Previous research has predominantly focused on the direct impact of soil pollution on live earthworms, overlooking the subsequent effects on earthworm-mediated soil, such as casts and burrow walls. Using 2D-terraria as incubation containers and the geophagous earthworm species Metaphire guillelmi, this study assessed the change in various properties of earthworm-mediated soil in both uncontaminated soils and Cd- and Pye-contaminated soils. Overall, both Cd and Pye overall improved the ammonium nitrogen (NH 4 -N), Olsen's phosphorus (Olsen-P) levels, and invertase and catalase activities while decreasing catalase activities in earthworm-mediated soil. They also fluctuating affected the pH, soil organic matter (SOM) content, soil urease, alkaline phosphatase activities, and microbial functional genes in the cast and burrow walls. These results indicated that earthworms remained crucial "ecosystem engineers" even in polluted soil. Additionally, differences were observed in the responses of properties between casts and burrow walls, showing unequal contributions of transit-through-gut and burrowing processes to soil modification. Specifically, transit-through-gut was found to have a more significant influence on soil NH + -N), Olsen's phosphorus (Olsen-P) levels, and invertase and catalase activities while decreasing catalase activities in earthworm-mediated soil. They also fluctuating affected the pH, soil organic matter (SOM) content, soil urease, alkaline phosphatase activities, and microbial functional genes in the cast and burrow walls. These results indicated that earthworms remained crucial "ecosystem engineers" even in polluted soil. Additionally, differences were observed in the responses of properties between casts and burrow walls, showing unequal contributions of transit-through-gut and burrowing processes to soil modification. Specifically, transit-through-gut was found to have a more significant influence on soil NH 4 + -N and Olsen-P content compared to burrowing behavior. Regarding the pattern of microbial functional genes in earthworm-associated compartments, results revealed that they differed significantly in casts from those in bulk soil and burrow walls under unpolluted conditions, with pollution-enhancing disparities among compartments. Furthermore, NH 4 + -N and Olsen-P content, urease, and catalase activities in burrow walls and/or casts were identified as potential biomarkers for soil pollution, exhibiting a clear dose-effect relationship. Developing such biomarkers could address ethical concerns related to conventional earthworm biomarkers that require sacrificing earthworms. This study provides insights into the consequences of soil pollution on earthworm-mediated soil components, highlighting the importance of considering the indirect effects of contaminants on soil ecosystems., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

PLACK syndrome (OMIM 616295) is a rare genodermatosis associated with peeling skin, leukonychia, acral punctate keratosis, cheilitis, and knuckle pads and is caused by loss-of-function mutations in the CAST gene, which encodes calpastatin, a calcium-dependent protease. This case report highlights a case of PLACK syndrome presenting with the unique findings of striate hyperkeratosis on the palms as well as life-threatening cardiomyopathy. We review why CAST mutations might impact cardiac function and raise awareness of the potential association between PLACK syndrome and cardiac manifestations., (© 2024 Wiley Periodicals LLC.)

Background: Various treatment approaches for individuals with ankle sprains can reduce treatment costs and enhance recovery. This study aimed to compare the efficacy of spring ankle braces with splints and casts in treating ankle sprains., Materials and Methods: This cross-sectional study involved 60 patients diagnosed with ankle sprains at the orthopedic clinic of Imam Khomeini Hospital in Jiroft in 2022. Following diagnosis confirmation through additional examinations and imaging, patients with ankle sprains not requiring surgery were selected and placed in two groups: one treated with spring ankle braces and the other with splints or casts. Both groups underwent a 4-week treatment regimen, comprising 30 individuals each. Data were collected and analyzed using SPSS version 26., Results: The average age of patients was 32.5 ± 13.4 years. Of the ankle sprain patients, 56.7% were male. Patients reported the highest satisfaction levels with the plaster cast treatment method. A statistically significant relationship was found between patient satisfaction and the treatment methods of spring ankle braces and plaster casting (P < 0.05). Patients treated with plaster casts reported the lowest pain levels, with a significant relationship between pain levels and the two treatment methods (P < 0.05). Range of motion results were similar for both treatment methods, while the cast treatment showed the highest incidence of skin complications. A significant relationship was observed between spring ankle braces and plaster casts regarding skin complications (P < 0.05)., Conclusion: Treating ankle sprains with plaster casts leads to higher satisfaction and lower pain levels compared to using spring ankle braces., (© 2024. The Author(s).)

The Coastal Creole pigs in Argentina are predominantly found in the wild and can trace their lineage directly back to the Iberian breeds introduced by Spanish colonizers. They currently stand as the sole Creole breed in the country recognized by the FAO. However, there exists a dearth of studies assessing their genetic potential within the swine industry. Therefore, this study aimed to genetically characterize the meat quality of Coastal Creole pigs based on seven single nucleotide polymorphisms (SNPs) within the Ryr1, PRKAG3, MC4R, H-FABP, and CAST genes. A total of N = 158 samples were collected from specimens distributed along the coastal region. Our findings revealed all loci to exhibit polymorphism, underscoring the population's remarkable genetic diversity. Furthermore, a higher frequency of alleles favorable for the PRKAG3 191I>V/200R>Q , MC4R 1426A>G , CAST 76872G>A , and Ryr1 1843C>T genes was observed, while alleles unfavorable predominated for H-FABP 1811G>C and CAST 638Ser>Arg . The results obtained in this research are highly encouraging, reflecting the genetic potential of these pigs to be utilized in swine production programs., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

An esthetic peri-implant soft tissue contour is a critical element of the success of implant restorations in the esthetic zone. Once the optimal transmucosal soft tissue profile is formed, it needs to be accurately replicated on the master cast. This clinical technique involves the utilization of a silicone putty positioning index placed in the patient's mouth to accurately duplicate the external contour of teeth and soft tissue. By combining this positioning index with the implant-supported interim crown, the 3D-printed initial cast, which was used to fabricate the interim crown, can be conveniently and efficiently transformed into a definitive master cast., (© 2023 The Authors. Journal of Prosthodontics published by Wiley Periodicals LLC on behalf of American College of Prosthodontists.)

Introduction: Postmortem evaluation of the human vascular system has a long history, with advancements ranging from dissections to modern imaging techniques like computed tomography (CT scan). This study designs a novel combination of Angiofil, a liquid radiopaque polymer, and latex, a flexible cast material, for cadaveric vascular analysis., Material & Methods: The aim was to synergize the advantages of both components, providing accurate radiological images and optimal dissection conditions. Three arterial territories (lateral circumflex femoral artery, profunda brachii artery, and radial artery) were injected and assessed through CT scans and dissections., Results: The Angiofil-latex mixture allowed successful visualization of the vascular networks, offering a simple, reproducible, and non-toxic approach. Quantitative assessments of the three territories, including diameters and lengths, showed comparable results between CT scan and dissection., Discussion: The technique precision and versatility make it an accessible and valuable tool for anatomical studies, potentially extending its application to MRI analyses. Overall, the Angiofil-latex combination presents a cost-effective solution for researchers, offering enhanced visibility and detailed anatomical insights for various applications, including anatomical variation studies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier GmbH.. All rights reserved.)

A meta-analysis including all relevant randomized controlled trials was conducted to compare soft bandage, splint and cast as the treatment of torus fracture. PubMed, Scopus, and Web of Science databases were searched in January 2023. Two comparisons were made: (1) splint versus cast, and (2) bandage versus rigid immobilization (i.e. splint or cast). Main outcomes were pain, clinical healing of the fracture and return to activities. Secondary outcomes were adverse events (skin issues, problems with cast/splint/bandage) and patient/parental satisfaction. Seven studies with 1550 patients were included. Splint was associated with higher pain scores at 3 days compared to cast (Mean difference [MD] 1.00, CI 0.06-1.94) and at 1 week (MD 1.46, CI 0.84-2.08, moderate-certainty evidence), but faster return to activities (at 3 weeks RR 1.77, CI 1.09-2.88, at 4 weeks RR 1.44, CI 1.11-1.82, moderate-certainty evidence). All torus fractures heal clinically within 3-4 weeks (low-certainty evidence). Bandage may lead to slightly higher pain score (MD 0.35, CI 0.04-0.66, moderate-certainty evidence) at first day after treatment compared to rigid immobilization, but no evidence of a difference was found in later time points. In conclusion, soft bandage or removable wrist splint seem to be optimal first-line treatment of distal forearm torus fracture., (© 2024. The Author(s).)

This study utilized FLUENT dynamic mesh simulation technology to simulate the temperature field distribution characteristics during the continuous casting (CC) process of 5 mm thick Zr 41.2 Ti 13.8 Cu 12.5 Ni 10.0 Be 22.5 (Vit1) bulk metallic glass (BMG), analyzed and discussed the amorphous forming ability of the Vit1 BMG plate prepared through CC. The results indicate that during the CC process, the temperature gradient and cooling rate of Vit1 BMG plate decrease with increasing distance from the cooling copper block surface and prolonged solidification time. Even at the lowest cooling rate, it still remains significantly higher than the critical cooling rate ( R c ) of Vit1 bulk amorphous alloy. The temperature variations recorded by the thermocouple during the alloy melt solidification process are in basic agreement with the simulation data. The experimental test and simulation results show that 5 mm thick Vit1 BMG slab can be prepared theoretically by continuous casting technology. Finally, XRD, DSC and TEM were used to analyze the amorphous formation ability and microstructure of the Vit1 BMG slab., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors.)

Introduction: Computed tomography can be used to screen and diagnose the presence of drug-filled packets in the body. We present an unusual computed tomography finding in a suspected body packer., Case Summary: A traveller suspected of being a body packer was brought to the emergency department complaining of low back pain. On examination, there was an abdominal cast circumferentially encasing his abdomen, which he alleged was part of the management of his lower back pain in his own country., Images: A plain computed tomogram of the abdomen and pelvis revealed that the cast was made of materials with a nodular appearance and heterogeneous density, which was different from that of a plaster of Paris cast. An investigation later confirmed the cast contained cocaine., Conclusion: Our case demonstrates how a body packer can traffic drugs outside their body for an alleged medical reason.

Earthworm could regulate their body concentration of arsenic via storage or excretion, and the ability of As efflux among different earthworms is not consistent. Here, whole and semi As exposure patterns with 0-10-30-60-100 mg kg -1 exposure concentrations were set to characterize the As efflux in geophagous earthworm, Metaphire guillelmi. Cast As (As-C) and earthworms' antioxidative responses were monitored to explore the efflux mechanisms under 30 mg kg -1 As-spiked soil (As30), besides, As concentration in earthworm tissue after egestion and dissection depurations were compared. In the whole exposure pattern, As concentration in gut content (As-G, 19.2-120.3 mg kg -1 ) surpassed that in the tissue (As-T, 17.2-53.2 mg kg -1 ), and they both increased with exposure concentrations. With the prolong time, they firstly increased and kept stable between day 10-15, then As-G increased while As-T decreased between day 15-20. In the semi-exposure pattern, both As-G and As-T decreased when M. guillelmi was transferred to clean soil for 5 days. During the 42-day incubation in As30, the antioxidative responses including reactive oxygen species (ROS), glutathione (GSH) and glutathione-S-transferase (GST) were firstly increased and then decreased, and As-C (13.9-43.9 mg kg -1 ) kept higher than As-G (14.2-35.1 mg kg -1 ). Significantly positive correlations were found between As-T and GSH, As-C and GST. Moreover, tissue As after dissection (11.6-22.9 mg kg -1 ) was obviously lower than that after egestion (11.4-26.4 mg kg -1 ), but significantly related to ROS and GSH. Taken together, M. guillelmi exhibited excellent capacity of As efflux, and GSH explained tissue As accumulation while GST facilitated the As elimination via cast. Besides, dissection instead of egestion revealed the As efflux in M. guillelmi more accurately. These findings contributed to a better understanding of how geophagous earthworm M. guillelmi regulated tissue As accumulation for As stress tolerance, and recommended an optimal depuration mode to characterize As accumulation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Genome editing in non-model bacteria is important to understand gene-to-function links that may differ from those of model microorganisms. Although species of the Burkholderia cepacia complex (Bcc) have great biotechnological capacities, the limited genetic tools available to understand and mitigate their pathogenic potential hamper their utilization in industrial applications. To broaden the genetic tools available for Bcc species, we developed RhaCAST, a targeted DNA insertion platform based on a CRISPR-associated transposase driven by a rhamnose-inducible promoter. We demonstrated the utility of the system for targeted insertional mutagenesis in the Bcc strains B. cenocepacia K56-2 and Burkholderia multivorans ATCC17616. We showed that the RhaCAST system can be used for loss- and gain-of-function applications. Importantly, the selection marker could be excised and reused to allow iterative genetic manipulation. The RhaCAST system is faster, easier, and more adaptable than previous insertional mutagenesis tools available for Bcc species and may be used to disrupt pathogenicity elements and insert relevant genetic modules, enabling Bcc biotechnological applications., Importance: Species of the Burkholderia cepacia complex (Bcc) have great biotechnological potential but are also opportunistic pathogens. Genetic manipulation of Bcc species is necessary to understand gene-to-function links. However, limited genetic tools are available to manipulate Bcc, hindering our understanding of their pathogenic traits and their potential in biotechnological applications. We developed a genetic tool based on CRISPR-associated transposase to increase the genetic tools available for Bcc species. The genetic tool we developed in this study can be used for loss and gain of function in Bcc species. The significance of our work is in expanding currently available tools to manipulate Bcc., Competing Interests: The authors declare no conflict of interest.

Background: The aim of this study was to compare the effects of four different immobilization methods [single sugar tong splint (SSTS), double sugar tong splint (DSTS), short arm cast (SAC), and long arm cast (LAC)] commonly used for restricting forearm rotation in the upper extremity., Methods: Forty healthy volunteers were included in the study. Dominant extremities were used for measurements. Basal pronation and supination of the forearm were measured with a custom-made goniometer, and the total rotation arc was calculated without any immobilization. Next, the measurements were repeated with the SAC, LAC, SSTS and DSTS. Each measurement was compared to the baseline value, and the percentage of rotation restriction was calculated., Results: The most superior restriction rates were observed for the LAC (p = 0.00). No statistically significant difference was detected between the SSTS and DSTS in terms of the restriction of supination, pronation or the rotation arc (p values, 1.00, 0.18, and 0.50, respectively). Statistically significant differences were not detected between the SAC and the SSTS in any of the three parameters (p values, 0.25; 1.00; 1.00, respectively). When the SAC and DSTS were compared, while there was no significant difference between the two methods in pronation (p = 0.50), a statistically significant difference was detected in supination (p = 0.01) and in the total rotation arc (p = 0.03)., Conclusion: The LAC provides superior results in restricting forearm rotation. The SAC and SSTS had similar effects on forearm rotation. The DSTS, which contains, in addition to the SSTS, a sugar tong portion above the elbow, does not provide additional rotational stability., (© 2024. The Author(s).)

(1) Background : Dislocations of the trapeziometacarpal joint (TMC) are uncommon in children and adolescents. Only a few isolated cases are reported in the literature. Therapeutic guidance is minimal and inconclusive. (2) Methods : The authors present four patients treated for this unusual lesion. We evaluated the evolution according to treatment, age, patient activity, and quickDASH. Despite the clear limitation of the small number of patients, it is relevant to try to better understand this lesion and its evolution. A systematic review of the literature was also conducted. (3) Results : This is the largest published series of TMC dislocations in children and adolescents. Patients included a 12-year-old girl treated conservatively with a poor quickDASH; a 9-year-old girl treated surgically with the Eaton-Littler technique for a new dislocation with a partially modified quickDASH; a 13-year-old boy with two necessary closed reductions for a new dislocation and a very good final quickDASH; and a 12-year-old boy treated with closed reduction and percutaneous fixation with excellent final results with quickDASH. (4) Conclusions : In the absence of scientific evidence, conservative treatment and ligament reconstruction did not provide good functionality. In contrast, closed reduction with percutaneous fixation provided excellent results. Therefore, the authors would recommend closed reduction and percutaneous needle fixation as an elective method to treat TMC dislocations in pediatric and adolescent patients.

Background: The Cannabis Abuse Screening Test (CAST) is a widely used screening tool for identifying patterns of cannabis use that have negative health or social consequences for both the user and others involved. This brief screening instrument has been translated into multiple languages, and several studies examining its psychometric properties have been published. However, studies on the factorial validity and psychometric properties of a Moroccan version of the CAST are not yet available. The objective of this study is to validate the CAST, translated, and adapted to the Moroccan Arabic dialect among persons with cannabis use., Methods: A total of 370 participants from an addictology center in Fez City, were selected over two phases to form the study sample. First, in phase I, exploratory factor analysis was employed to evaluate the factor structure in the pilot sample (n 1  = 150). Subsequently, in the second phase (Phase II), confirmatory factor analysis was utilized to confirm this structure in the validation sample (n 2  = 220). All statistical analyses were carried out using the R program., Results: The CFA unveiled a three-factor structure that showed a good overall fit (χ2/df = 2.23, RMSEA = 0.07, SRMR = 0.02, CFI = 0.99, NFI = 0.98) and satisfactory local parameters (standardized factor loadings between 0.72 and 0.88). The model demonstrates satisfactory reliability and convergent validity, as evidenced by the acceptable values of composite reliability (CR) (0.76-0.88) and average variance extracted (AVE) (0.62-0.78), respectively. The square roots of the AVE exceeded the correlations of the factor pairs, and the heterotrait-monotrait (HTMT) ratio of the correlation values was below 0.85, indicating acceptable discriminant validity., Conclusion: The reliability, convergent validity, and discriminant validity tests all demonstrated that the Moroccan version of the CAST performed well and can be considered a valid tool for screening of problematic cannabis use., (© 2024. The Author(s).)

Aims: Offloading mechanical tissue stress is arguably the most important of multiple interventions needed to heal diabetes-related foot ulcers. This is the 2023 International Working Group on the Diabetic Foot (IWGDF) evidence-based guideline on offloading interventions to promote healing of foot ulcers in persons with diabetes. It serves as an update of the 2019 IWGDF guideline., Materials and Methods: We followed the GRADE approach by devising clinical questions and important outcomes in the PICO (Patient-Intervention-Control-Outcome) format, undertaking a systematic review and meta-analyses, developing summary of judgement tables and writing recommendations and rationales for each question. Each recommendation is based on the evidence found in the systematic review, expert opinion where evidence was not available, and a careful weighing of GRADE summary of judgement items including desirable and undesirable effects, certainty of evidence, patient values, resources required, cost effectiveness, equity, feasibility, and acceptability., Results: For healing a neuropathic plantar forefoot or midfoot ulcer in a person with diabetes, use a non-removable knee-high offloading device as the first-choice offloading intervention. If contraindications or patient intolerance to non-removable offloading exist, consider using a removable knee-high or ankle-high offloading device as the second-choice offloading intervention. If no offloading devices are available, consider using appropriately fitting footwear combined with felted foam as the third-choice offloading intervention. If such a non-surgical offloading treatment fails to heal a plantar forefoot ulcer, consider an Achilles tendon lengthening, metatarsal head resection, joint arthroplasty, or metatarsal osteotomy. For healing a neuropathic plantar or apex lesser digit ulcer secondary to flexibile toe deformity, use digital flexor tendon tenotomy. For healing rearfoot, non-plantar or ulcers complicated with infection or ischaemia, further recommendations have been outlined. All recommendations have been summarised in an offloading clinical pathway to help facilitate the implementation of this guideline into clinical practice., Conclusion: These offloading guideline recommendations should help healthcare professionals provide the best care and outcomes for persons with diabetes-related foot ulcers and reduce the person's risk of infection, hospitalisation and amputation., (© 2023 The Authors. Diabetes/Metabolism Research and Reviews published by John Wiley & Sons Ltd.)

Direct tubular injury caused by several medications, especially chemotherapeutic drugs, is a common cause of AKI. Inhibition or loss of cyclin-dependent kinase 12 (CDK12) triggers a transcriptional elongation defect that results in deficiencies in DNA damage repair, producing genomic instability in a variety of cancers. Notably, 10-25% of individuals developed AKI after treatment with a CDK12 inhibitor, and the potential mechanism is not well understood. Here, we found that CDK12 was downregulated in the renal tubular epithelial cells in both patients with AKI and murine AKI models. Moreover, tubular cell-specific knockdown of CDK12 in mice enhanced cisplatin-induced AKI through promotion of genome instability, apoptosis, and proliferative inhibition, whereas CDK12 overexpression protected against AKI. Using the single molecule real-time (SMRT) platform on the kidneys of CDK12 RTEC+/- mice, we found that CDK12 knockdown targeted Fgf1 and Cast through transcriptional elongation defects, thereby enhancing genome instability and apoptosis. Overall, these data demonstrated that CDK12 knockdown could potentiate the development of AKI by altering the transcriptional elongation defect of the Fgf1 and Cast genes, and more attention should be given to patients treated with CDK12 inhibitors to prevent AKI., Competing Interests: Competing Interests: The authors have declared that no competing interest exists., (© The author(s).)

In the healthcare system, lower leg fractures remain relevant, incurring costs related to surgical treatment, hospitalization, and rehabilitation. The duration of treatment may vary depending on the individual case and its severity. Casting as a post-surgical fracture treatment is a common method in human and experimental veterinary medicine. Despite the high importance of sheep in preclinical testing materials for osteosynthesis, there is no standardised cast system ensuring proper stabilisation and functionality of hind limbs during the healing of tibia fractures or defects. Existing treatment approaches for tibial osteosynthesis in laboratory animal science include sling hanging, external fixators, or former Achilles tendon incision. These methods restrict animal movement for 4-6 weeks, limit species-typical behaviour, and impact social interactions. Our pilot study introduces a Standardised Walking Cast (SWC) for sheep, enabling immediate physiological movement post surgery. Seven Rhone sheep (female, 63.5 kg ± 6.45 kg) each with a single tibia defect (6 mm mechanical drilled defect) underwent SWC application for 4 weeks after plate osteosynthesis. The animals bore weight on their operated leg from day one, exhibiting slight lameness (grade 1-2 out of 5). Individual step lengths showed good uniformity (average deviation: 0.89 cm). Group housing successfully started on day three after surgery. Weekly X-rays and cast changes ensured proper placement, depicting the healing process. This study demonstrates the feasibility of using an SWC for up to 72 kg of body weight without sling hanging via ceiling mounting or external fixation techniques. Allowing species-typical movement and social behaviour can significantly improve the physiological behaviour of sheep in experiments, contributing to refinement.

Background: Risk stratification is important in patients with post-cardiac arrest syndrome. The Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia (CAST) and revised CAST (rCAST) scores have been well validated for predicting neurological outcomes, particularly for conventionally resuscitated patients with post-cardiac arrest syndrome. However, no studies have evaluated patients undergoing extracorporeal cardiopulmonary resuscitation., Methods and Results: Adult patients with out-of-hospital cardiac arrest who underwent extracorporeal cardiopulmonary resuscitation were analyzed in this retrospective observational multicenter cohort study. We validated the accuracy of the CAST/rCAST scores for predicting neurological outcomes at 30 days. Moreover, we compared the predictive performance of these scores with the TiPS65 risk score derived from patients with out-of-hospital cardiac arrest who were resuscitated using extracorporeal cardiopulmonary resuscitation. A total of 1135 patients were analyzed. The proportion of patients with favorable neurological outcomes was 16.6%. In the external validation, the area under the receiver operating characteristic curve of the CAST score was significantly higher than that of the rCAST score (area under the receiver operating characteristic curve 0.677 versus 0.603; P <0.001), but there was no significant difference with that of the TiPS65 score (versus 0.633; P =0.154). Both CAST/rCAST risk scores showed good calibration (Hosmer-Lemeshow test: P =0.726 and 0.674), and the CAST score showed significantly better predictability in net reclassification compared with the rCAST ( P <0.001) and TiPS65 scores ( P =0.001)., Conclusions: The prognostic accuracy of the CAST score was significantly better than that of other risk scores in net reclassification. The CAST score may help to predict neurological outcomes in patients with out-of-hospital cardiac arrest who undergo extracorporeal cardiopulmonary resuscitation. However, the predictive value of the CAST score was not sufficiently high for clinical application., Registration: URL: https://center6.umin.ac.jp/cgi-open-bin/ctr&#95;e/ctr&#95;view.cgi?recptno=R000041577; Unique identifier: UMIN000036490.

Purpose: Different studies have shown that weightbearing is safe in stable transsyndesmotic, isolated lateral simple ankle fractures. Despite this evidence, AO guidelines still recommend immobilization with above-the-knee cast for 4-6 weeks for these fractures. The objective of this study was to compare the outcomes of mobilization and weightbearing to those of immobilization and non-weightbearing in patients with stable transsyndesmotic, lateral isolated simple ankle fractures., Methods: Fifty patients were randomly assigned to permissive weightbearing in a walking boot or non-weightbearing immobilization using a below-the-knee cast. Primary outcome was ankle functionality as scored by the Olerud-Molander Ankle Score (OMAS). Secondary outcomes were radiological displacement of fracture, range of motion (ROM), calf circumference, and RAND 36-item health survey. Patients were in follow-up for 24 months., Results: Ankle functionality after six and twelve weeks was significantly higher for the intervention group, with respectively 30 points (p = 0.001) and 10 points (p = 0.015) of difference. ROM improved significantly in the intervention group after six weeks. All fractures showed radiological progression of fracture healing. RAND 36-item showed differences in both physical (60.3 vs. 46.3, p = 0.017) and mental (78.5 vs. 58.2, p = 0.034) components in favor of the intervention group. In 16% of patients who initially showed stable fractures on radiographic imaging, joint dislocation was identified on weightbearing radiographs prior to randomization, leading to exclusion., Conclusion: Weightbearing and mobilization using a walking boot may be a safe treatment for patients with stable Weber B fractures., (© 2023. The Author(s).)

Transposons are mobile genetic elements that have invaded all domains of life by moving between and within their host genomes. Due to their mobility (or transposition), transposons facilitate horizontal gene transfer in bacteria and foster the evolution of new molecular functions in prokaryotes and eukaryotes. As transposition can lead to detrimental genomic rearrangements, organisms have evolved a multitude of molecular strategies to control transposons, including genome defense mechanisms provided by CRISPR-Cas systems. Apart from their biological impacts on genomes, DNA transposons have been leveraged as efficient gene insertion vectors in basic research, transgenesis and gene therapy. However, the close to random insertion profile of transposon-based tools limits their programmability and safety. Despite recent advances brought by the development of CRISPR-associated genome editing nucleases, a strategy for efficient insertion of large, multi-kilobase transgenes at user-defined genomic sites is currently challenging. The discovery and experimental characterization of bacterial CRISPR-associated transposons (CASTs) led to the attractive hypothesis that these systems could be repurposed as programmable, site-specific gene integration technologies. Here, we provide a broad overview of the molecular mechanisms underpinning DNA transposition and of its biological and technological impact. The second focus of the article is to describe recent mechanistic and functional analyses of CAST transposition. Finally, current challenges and desired future advances of CAST-based genome engineering applications are briefly discussed., (© 2023 The Authors. FEBS Open Bio published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)

The effects of occupational isocyanate exposure range from asthma and contact dermatitis to neurotoxicity and cancer. Respiratory sensitization due to orthopedic cast application has been well documented. This study aims to compare the safety of standard-of-care fiberglass casts and a novel waterproof cast alternative by measuring the amount of isocyanate released during off-gassing over time. A 3D-printed arm simulator with comparable casing material amounts was placed in a sealed chamber. An isocyanate-sensing color-changing (SafeAir) tag was used to measure the levels of toxic exposure. Triplicate trials were conducted across all time periods (15 min, 1 h, and 24 h) and conditions. The bare arm simulator and freshly opened tags served as negative controls. Normalized pixel intensity indexes and isocyanate release estimates in ppb were derived from ImageJ-analyzed SafeAir tag photos. Fiberglass casts exhibited greater isocyanate release than both the waterproof alternative ( p = 0.0002) and no-cast controls ( p = 0.0006), particularly at 24 h. The waterproof alternative and no-cast control did not statistically differ ( p = 0.1603). Therefore, the waterproof alternative released less isocyanate than the fiberglass casts. Waterproof cast alternatives may be safer than fiberglass by limiting medical professionals' exposure to toxic isocyanates and, thus, decreasing their risk of suffering occupational asthma.

Non-Human Primates (NHPs) are particularly relevant for preclinical studies during the development of inhaled biologics. However, aerosol inhalation in NHPs is difficult to evaluate due to a low lung deposition fraction and high variability. The objective of this study was to evaluate the influence of mesh nebulizer parameters to improve lung deposition in macaques. We developed a humidified heated and ventilated anatomical 3D printed macaque model of the upper respiratory tract to reduce experiments with animals. The model was compared to in vivo deposition using 2D planar scintigraphy imaging in NHPs and demonstrated good predictivity. Next, the anatomical model was used to evaluate the position of the nebulizer on the mask, the aerosol particle size and the aerosol flow rate on the lung deposition. We showed that placing the mesh-nebulizer in the upper part of the mask and in proximal position to the NHP improved lung delivery prediction. The lower the aerosol size and the lower the aerosol flow rate, the better the predicted aerosol deposition. In particular, for 4.3 ± 0.1 µm in terms of volume mean diameter, we obtained 5.6 % ± 0.2 % % vs 19.2 % ± 2.5 % deposition in the lung model for an aerosol flow rate of 0.4 mL/min vs 0.03 mL/min and achieved 16 % of the nebulizer charge deposited in the lungs of macaques. Despite the improvement of lung deposition efficiency in macaques, its variability remained high (6-21 %)., Competing Interests: Declaration of Competing Interest M. Cabrera has nothing to disclose. D. Le Pennec has nothing to disclose. J. Pardessus has nothing to disclose. S. Le Guellec is employed by Diffusion Technique Française (St Etienne, France). R. MacLoughlin is employed by Aerogen (Galway, Ireland). L. Vecellio was employed by DTF Medical from 2001 to 2018, by Nemera from 2018 to 2020 and is the inventor of the patent PCT/FR2022/052203, N. Heuzé-Vourc'h is a co-founder and scientific expert for Cynbiose Respiratory. In the past years, she has been paid as scientific expert (Eli Lilly (France), Ablynx (Belgium) and has financial relationships with private entities (Aerogen (Ireland), Ablynx (Belgium), outside the submitted work., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Introduction  A systematic review and meta-analysis of randomized controlled trials was conducted to compare surgical treatment using open reduction and internal fixation (ORIF) with volar locking plates (VLP) to conservative treatment with closed reduction and immobilization in elderly patients aged ≥60 years with acute displaced distal radius fractures. Methods  A search of the MEDLINE, Scopus, and Central Register of Controlled Trials (CENTRAL) databases was conducted. Clinical and radiographic measures at 12 months were compared between groups by pooling the mean difference. The complication rates were compared by pooling relative risk ratios. Pooled mean differences of Disabilities of the Arm, Shoulder, and Hand (DASH) and Patient-Rated Wrist Evaluation (PRWE) results were compared with the published minimal clinically important difference (MCID) to evaluate the clinical relevance of the results. Results  The initial search yielded 766 records, from which 6 articles were selected for the final analysis. The results of the DASH questionnaire at 12 months of follow-up were significantly lower in the surgical treatment group with a mean difference (MD) of -3.61 points (95% confidence interval [CI]: -6.48 to -0.73). No statistically significant difference was found in the PRWE questionnaire (MD = -3.14 points [95% CI: -7.32 to 1.04]). Radiological results were significantly better in the surgical treatment group and no significant difference in the overall complication rate between the groups was detected. Found MD for DASH and PRWE did not reach the published MCIDs. Conclusion  This study suggests that for elderly patients aged ≥60 years with acute displaced distal radius fractures, surgical treatment using ORIF with VLP does not provide clinically relevant benefits compared with conservative treatment with closed reduction and immobilization at the 12-month follow-up, despite demonstrating better radiological results., Competing Interests: Conflict of Interest None declared., (Thieme. All rights reserved.)

Background: Monitoring the prevalence of problematic cannabis use is an important public health issue. International surveys need invariant measurement tools to allow reliable comparisons across countries and between sexes. The Cannabis abuse screening test (CAST) has been developed for this purpose. This study is the first assessing its country and sex invariance in a sample of European pupils., Methods: The data come from the self-administered questionnaires completed in 2019 by pupils aged 15-16 in the European school survey project (Espad). The analytical sample was restricted to the 17 countries where at least 300 pupils reported a previous-year cannabis use (n = 8740); multigroup confirmatory factor analyses were used to assess the configural, metric and scalar invariance of the CAST toward country and sex in the 2019 Espad release., Results: Configural, metric and scalar invariance toward country hold for the 17 countries: Austria, Bulgaria, Croatia, Czech Republic, Denmark, Estonia, Finland, France, Georgia, Greece, Italia, Latvia, Poland, Portugal, Slovakia, Slovenia and Spain. Scalar invariance toward sex was met in the 17 countries as a whole and in 11 of the 12 countries where the test could be run. Scalar invariance toward country was met with 6 additional countries comprising at least 250 respondents: Ireland, Lithuania, Malta, Montenegro, the Netherlands and Norway., Conclusion: The CAST is a suitable test for comparing the measurement of problematic cannabis use amongst adolescents in Europe., Competing Interests: Declaration of Competing Interest The authors have no conflicts of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: We aimed to compare radiologically and clinically closed reduction circular casting (CRCC) and volar locking plate (VLP) treatment options in elderly patients over 75 years with intraarticular distal radius fracture (DRF)., Material and Method: Elderly patients aged ≥75 years with at least one year of follow-up from the clinic archive who underwent conservative (CRCC) and surgical (VLP) treatment for AO type C DRF were retrospectively included in the study. Thirty-seven patients treated conservatively with CRCC and 31 treated surgically with VLP were compared as two groups. Quick Disability of the Arm, Shoulder, and Hand (QDASH) and Visual Analog scores (VAS) were evaluated functionally. In addition, a rapid assessment of physical activity (RAPA) score evaluation was performed since these patients were elderly. In addition, radiologic findings, wrist range of motion, and complications were evaluated., Results: There was no difference between the CRCC and VLP groups regarding QDASH, VAS, and RAPA scores at the last follow up. Radiologically, there were significant differences between the groups regarding radial height, volar tilt, radial inclination and joint stepping. (respectively p= <0.001 , p= <0.001, p= <0.001, p= <0.001)., Conclusion: In elderly patients over 75 years of age with intra-articular DRF, surgical treatment with VLP results in better radiologic results compared to conservative treatment with CRCC, although both treatment options lead to similar results in terms of functional outcomes., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 Delhi Orthopedic Association. All rights reserved.)

Purpose: There is currently no consensus on nonoperative management in adult patients after a stable type B ankle fracture. The aim of this review is to compare a removable orthosis versus a cast regarding safety and functional outcome in the NOM of stable type B ankle fractures., Methods: A systematic review and meta-analysis were performed using randomized clinical trials and observational studies. The methodological quality of the included studies was assessed with the methodological index for non-randomized studies instrument. Nonoperative management was compared using the number of complications and functional outcome measured using the Olerud and Molander Score (OMAS) or the American Academy of Orthopaedic Surgeons Ankle Score., Results: Five studies were included. Two were randomized clinical trials, and three were observational studies, including a total of 516 patients. A meta-analysis showed statistically significant higher odds of developing complications in the cast group [odds ratio (OR), 4.67 (95% confidence interval (CI) 1.52-14.35)]. Functional outcome in OMAS did not vary significantly at 6 weeks, mean difference (MD) - 6.64 (95% CI - 13.72 to + 0.45), and at 12 weeks, MD - 6.91 (95% CI - 18.73 to + 4.91). The mean difference of functional outcome in OMAS at 26 weeks or longer was significantly better in the removable orthosis group; MD - 2.63 (95% CI - 5.01 to - 0.25)., Conclusion: Results of this systematic review and meta-analysis show that a removable orthosis is a safe alternative type of NOM, as complication numbers are significantly lower in the orthosis group. In addition, no statistically significant differences were found in terms of functional outcome between a removable orthosis and a cast at 6 and 12 weeks. The 6-week and the 26-week OMAS results show that in patients with stable type B ankle fractures, a removable orthosis is non-inferior to a cast in terms of functional outcome., (© 2022. The Author(s).)

The mobilization of arsenic (As) in paddy soil has received much attention because it might accelerate the transfer of As from soil to rice. This study aims to elucidate whether earthworms can mobilize As through their casts. Cast samples were collected from 23 different paddy fields in the Red River delta. We first analysed different forms of As through fractionation and then performed batch experiments under reducing conditions to identify factors that govern the mobility of As in casts. Because the dissociation of casts may induce colloids that carry As, the colloidal properties of cast suspensions were also examined. The median value of As in casts (obtained from aqua regia digestion) was 5.11 mg kg -1 , which was lower than that in the surrounding soil (6.7 mg kg -1 ). Compared with the surrounding soil, casts contain less As, possibly because cast As is more labile and more easily lost due to leaching. Various processes, including the reductive dissolution of Fe oxides, decomposition of organic matter, and sorption competition of soluble anionic substances, such as P, Si and DOC, were found to strongly correlate with the release of As from casts. We propose that earthworms, via their casts, may accelerate the As cycle in paddy soils, potentially intensifying As exposure to human health. The dissociation of cast could release colloids containing As; therefore, the cotransport of As with cast-induced colloids should also be considered in future works., Competing Interests: Declaration of competing interest The author declares that he has no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

The loss of skeletal muscle strength mid-life in females is associated with the decline of estrogen. Here, we questioned how estrogen deficiency might impact the overall skeletal muscle phosphoproteome after contraction, as force production induces phosphorylation of several muscle proteins. Phosphoproteomic analyses of the tibialis anterior muscle after contraction in two mouse models of estrogen deficiency, ovariectomy (Ovariectomized (Ovx) vs. Sham) and natural aging-induced ovarian senescence (Older Adult (OA) vs. Young Adult (YA)), identified a total of 2,593 and 3,507 phosphopeptides in Ovx/Sham and OA/YA datasets, respectively. Further analysis of estrogen deficiency-associated proteins and phosphosites identified 66 proteins and 21 phosphosites from both datasets. Of these, 4 estrogen deficiency-associated proteins and 4 estrogen deficiency-associated phosphosites were significant and differentially phosphorylated or regulated, respectively. Comparative analyses between Ovx/Sham and OA/YA using Ingenuity Pathway Analysis (IPA) found parallel patterns of inhibition and activation across IPA-defined canonical signaling pathways and physiological functional analysis, which were similarly observed in downstream GO, KEGG, and Reactome pathway overrepresentation analysis pertaining to muscle structural integrity and contraction, including AMPK and calcium signaling. IPA Upstream regulator analysis identified MAPK1 and PRKACA as candidate kinases and calcineurin as a candidate phosphatase sensitive to estrogen. Our findings highlight key molecular signatures and pathways in contracted muscle suggesting that the similarities identified across both datasets could elucidate molecular mechanisms that may contribute to skeletal muscle strength loss due to estrogen deficiency.

Purpose: The purpose of the study was to compare the efficacy of 6 different commercially available waterproof cast protectors in their ability to maintain a dry environment and evaluate whether cast protectors perform better than a plastic bag secured with tape in keeping casts dry., Methods: We enrolled 23 adult participants to test 6 different commercially available cast protectors and a plastic bag. Participants trialed all cast protectors twice, with and without motion, by fully submerging each cast protector in water with a paper towel held between their index and middle fingers. Moisture accumulation within the cast protectors was estimated by the change in weight of paper towel. An analysis of variance test was performed to compare differences between cast protectors in their ability to maintain a dry internal environment., Results: The plastic bag showed an average moisture accumulation of 5.50 g without motion compared with all other cast protectors, which had 0.0 g of moisture accumulation. One cast protector and the plastic bag had an average moisture accumulation of 0.46 g and 4.51 g with motion compared to all other cast protectors. The plastic bag was ranked the worst by 100% of participants., Conclusions: Cast protectors appear to offer superior protection from moisture compared with a plastic bag., Type of Study/level of Evidence: Therapeutic IV., (Copyright © 2023 American Society for Surgery of the Hand. Published by Elsevier Inc. All rights reserved.)

To spread, transposons must integrate into target sites without disruption of essential genes while avoiding host defense systems. Tn7-like transposons employ multiple mechanisms for target-site selection, including protein-guided targeting and, in CRISPR-associated transposons (CASTs), RNA-guided targeting. Combining phylogenomic and structural analyses, we conducted a broad survey of target selectors, revealing diverse mechanisms used by Tn7 to recognize target sites, including previously uncharacterized target-selector proteins found in newly discovered transposable elements (TEs). We experimentally characterized a CAST I-D system and a Tn6022-like transposon that uses TnsF, which contains an inactivated tyrosine recombinase domain, to target the comM gene. Additionally, we identified a non-Tn7 transposon, Tsy, encoding a homolog of TnsF with an active tyrosine recombinase domain, which we show also inserts into comM. Our findings show that Tn7 transposons employ modular architecture and co-opt target selectors from various sources to optimize target selection and drive transposon spread., Competing Interests: Declaration of interests F.Z. is a scientific advisor and cofounder of Editas Medicine, Beam Therapeutics, Pairwise Plants, Arbor Biotechnologies, Proof Diagnostics, and Aera Therapeutics. F.Z. is a scientific advisor for Octant. G.F., M.K., and F.Z. are co-inventors on a provisional patent application filed by Broad relating to this work., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Distal forearm fractures are the most common pediatric fractures. This study aimed to investigate the effectiveness of below-elbow cast treatment for displaced distal forearm fractures in children compared to above-elbow cast through meta-analysis of randomized controlled trials., Methods: Several databases from January 1, 2000 until October 1, 2021 were searched for randomized controlled trials that assessed below versus above-elbow cast treatment of displaced distal forearm fractures in pediatric patients. The main meta-analysis comparison was based on the relative risk of loss of fracture reduction between children undergoing below versus above-elbow cast treatment. Other outcome measures including re-manipulation and cast-related complications were also investigated., Results: Nine studies were eligible of the 156 articles identified, with a total of 1049 children. Analysis was undertaken for all included studies with a sensitivity analysis conducted for studies with high quality. In the sensitivity analysis, the relative risks of loss of fracture reduction (relative risk = 0.6, 95% confidence interval = 0.38, 0.96) and re-manipulation (relative risk = 0.3, 95% confidence interval = 0.19, 0.48) between the below and above-elbow cast groups were in favor of below-elbow cast and statistically significant. Cast-related complications were in favor of below-elbow cast but did not attain statistical significance (relative risk = 0.45, 95% confidence interval = 0.05, 3.99). Loss of fracture reduction was noted in 28.9% of patients treated with above-elbow cast and 21.5% in below-elbow cast. Re-manipulation was attempted in 48.1% versus 53.8% of children who lost fracture reduction in the below-elbow cast and above-elbow cast groups, respectively., Conclusion: Below-elbow cast treatment was favored, with statistical significance, in terms of loss of fracture reduction and re-manipulation, and was not associated with a higher risk of cast-related complications. The accumulative evidence currently does not support above-elbow cast treatment and below-elbow cast treatment should be the mainstay for displaced distal forearm fractures in children., Level of Evidence: Level I, meta-analysis of therapeutic level I studies., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2023.)

ELKS proteins play a key role in organizing intracellular vesicle trafficking and targeting in both neurons and non-neuronal cells. While it is known that ELKS interacts with the vesicular traffic regulator, the Rab6 GTPase, the molecular basis governing ELKS-mediated trafficking of Rab6-coated vesicles, has remained unclear. In this study, we solved the Rab6B structure in complex with the Rab6-binding domain of ELKS1, revealing that a C-terminal segment of ELKS1 forms a helical hairpin to recognize Rab6B through a unique binding mode. We further showed that liquid-liquid phase separation (LLPS) of ELKS1 allows it to compete with other Rab6 effectors for binding to Rab6B and accumulate Rab6B-coated liposomes to the protein condensate formed by ELKS1. We also found that the ELKS1 condensate recruits Rab6B-coated vesicles to vesicle-releasing sites and promotes vesicle exocytosis. Together, our structural, biochemical, and cellular analyses suggest that ELKS1, via the LLPS-enhanced interaction with Rab6, captures Rab6-coated vesicles from the cargo transport machine for efficient vesicle release at exocytotic sites. These findings shed new light on the understanding of spatiotemporal regulation of vesicle trafficking through the interplay between membranous structures and membraneless condensates., Competing Interests: Conflict of interest The authors declare no competing financial interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

CRISPR-associated transposons (CASTs) are natural RNA-directed transposition systems. We demonstrate that transposon protein TniQ plays a central role in promoting R-loop formation by RNA-guided DNA-targeting modules. TniQ residues, proximal to CRISPR RNA (crRNA), are required for recognizing different crRNA categories, revealing an unappreciated role of TniQ to direct transposition into different classes of crRNA targets. To investigate adaptations allowing CAST elements to utilize attachment sites inaccessible to CRISPR-Cas surveillance complexes, we compared and contrasted PAM sequence requirements in both I-F3b CAST and I-F1 CRISPR-Cas systems. We identify specific amino acids that enable a wider range of PAM sequences to be accommodated in I-F3b CAST elements compared with I-F1 CRISPR-Cas, enabling CAST elements to access attachment sites as sequences drift and evade host surveillance. Together, this evidence points to the central role of TniQ in facilitating the acquisition of CRISPR effector complexes for RNA-guided DNA transposition., Competing Interests: Declaration of interests Cornell University has filed patent applications related to this system with M.T.P., J.E.P., and E.H.K. as inventors. The J.E.P. lab has corporate funding for research that is not directly related to the work in this publication., (Copyright © 2023 Elsevier Inc. All rights reserved.)

The cytomatrix at the active zone-associated structural protein (CAST) and its homologue, named ELKS, being rich in glutamate (E), leucine (L), lysine (K), and serine (S), belong to a family of proteins that organize presynaptic active zones at nerve terminals. These proteins interact with other active zone proteins, including RIMs, Munc13s, Bassoon, and the β subunit of Ca 2+ channels, and have various roles in neurotransmitter release. A previous study showed that depletion of CAST/ELKS in the retina causes morphological changes and functional impairment of this structure. In this study, we investigated the roles of CAST and ELKS in ectopic synapse localization. We found that the involvement of these proteins in ribbon synapse distribution is complex. Unexpectedly, CAST and ELKS, in photoreceptors or in horizontal cells, did not play a major role in ribbon synapse ectopic localization. However, depletion of CAST and ELKS in the mature retina resulted in degeneration of the photoreceptors. These findings suggest that CAST and ELKS play critical roles in maintaining neural signal transduction in the retina, but the regulation of photoreceptor triad synapse distribution is not solely dependent on their actions within photoreceptors and horizontal cells.

Background: The current study aims to investigate the clinical efficacy of closed reduction and cast immobilization for patients with developmental dysplasia of the hip (DDH) who failed Pavlik harness treatment., Methods: Patients with DDH who underwent cast immobilization under general anaesthesia after the failure of the Pavlik harness or Tübingen brace treatment between January 2015 and December 2020 were retrospectively recruited. General information, including Graf classification of initial diagnosis, initial treatment, age of cast immobilization, IHDI classification, AI index, avascular necrosis (AVN), and residual dysplasia, was collected. The incidence of AVN and late acetabular dysplasia (LACD) was also estimated. Moreover, factors related to AVN and LACD were investigated by multiple logistic regression analysis., Results: Thirty-four patients (47 hips) were finally included in the current study. Of these patients, 31 hips (66.0%) were successfully treated with closed reduction and cast immobilization. Open reduction was successfully performed in 16 hips (34.0%). Till the latest follow-up, LACD and AVN were found in 13 (27.7%) and 10 (21.3%) hips, respectively. In the open reduction group, type III and IV of the IHDI classification and type IV of the Ultrasound Graf classification were significantly higher when compared with the closed reduction group. Multiple logistic regression showed that failure of closed reduction was related to the initial types of the Ultrasound Graf and IHDI classifications., Conclusions: Although the success rate of closed reduction after early harness failure in DDH is only 66%, we still advocate closed reduction as a first-line treatment for children who have failed sling treatment. Even if closed reduction fails, open reduction can still achieve acceptable results., (© 2023 Royal Australasian College of Surgeons.)

Background and Aims: Both casts and braces can be used for post-operational immobilization of ankle fractures. This meta-analysis aimed to assess the complications and functional effects of the two types of immobilization., Material and Methods: PubMed, Embase, Cochrane, and CNKI was searched for randomized controlled trials (published between Jan 1, 1950, and March 2022). Relative risk (RR) or standard mean difference (SMD) with a 95% confidence interval (CI) was used to present the outcomes. The pooled data were assessed by using the fixed-effects model or random-effects model., Results: A total of 5 randomized controlled studies involving 930 subjects were included according to our inclusion criteria. On the ankle score at 6w,12w and 52w, there was no statistically significant difference between the two groups. In terms of 6w, the brace group showed better ankle dorsiflexion (MD = 6.78, 95% CI 0.56-13.00, p  = 0.03) and plantar flexion (MD = 6.58, 95% CI 1.60-11.55, p  = 0.01) than the cast group. The wound complications (RR = 3.49, 95% CI 1.32 to 9.24, p  = 0.01) and total complications (RR = 3.54, 95% CI 1.92 to 6.50, p  < 0.0001) in the brace group were three times more than that in the cast group. There was no statistically significant difference between the two groups in the non-wound complications. There was no statistically significant difference between the two groups in the time of going back to work, swelling of the ankle, and atrophy of the calf muscle., Conclusion: The short-term and long-term functional outcomes after postoperative treatment of adult ankle fractures with braces are similar to those with casts. The usage of braces may cause three times more wound complications than that of casts., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Li, Xie, Zhang, Liu, Xu and Yang.)

Studies have reported a high percentage of ankle fracture dislocations with secondary loss of reduction during primary treatment with a splint or cast. This study aimed to assess the rate of secondary loss of reduction in unimalleolar ankle fracture dislocations treated primarily with a cast or external fixator, identify the potential influence of fracture morphology, and investigate the potential implications. Unimalleolar ankle fracture dislocations with and without posterior malleolar fracture between 2011 and 2020 were included. Patients were categorized into two groups, depending on the method of temporary treatment. Fracture morphology, time to definitive surgery, and soft-tissue complications were compared. Of 102 patients, loss of reduction tended to occur more often in the cast group (17.3%) than in the external fixator group (6.0%). The presence of a posterior malleolar fracture did not have a significant influence on loss of reduction in cast immobilization; however, the fragment proved to be significantly bigger in cases with loss of reduction. No statistically significant differences in soft tissue complications or time to definitive surgery were found. Surgeons should consider the application of interval external fixation in the primary treatment of unimalleolar ankle fracture dislocations with additional posterior malleolar fractures.

Background: The best choice of orthosis in the treatment of acute Achilles tendon rupture is still under debate., Objective: To investigate if choice of orthosis in the first 3 weeks of treatment affected patient reported outcome (Achilles tendon Total Rupture Score (ATRS)), tendon elongation (Achilles Tendon Resting Angle (ATRA) and Heel Rise Height (HRH)) and re-rupture., Methods: Registry study in the Danish Achilles tendon Database. Patients treated with cast and patients treated with walker in the first 3 weeks of treatment were compared using a linear mixed-effects model adjusted for potential confounders., Results: 1304 patients were included in the study. No clinically relevant difference was found: Adjusted mean difference (using walker the whole period as reference)(95% CI) ATRS after 1 year = 0.1(-3.0; 4.1), ATRS after 6 months = 2.0(-4.5; 5.8), ATRS after 2 years = 3.0(-0.7; 7.0), HRH difference = 0.6(-6.6; 8.2), ATRA difference = 0.03°(-1.5; 1.6), re-rupture(odds ratio) = 0.812(0.4; 1.61)., Conclusion: Patients treated with cast the first 3 weeks after acute Achilles tendon rupture did not have better treatment outcome than patients treated with walker., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)

CRISPR-Cas systems have been co-opted by Tn7-like transposable elements to direct RNA-guided transposition. Type V-K CRISPR-associated transposons rely on the concerted activities of the pseudonuclease Cas12k, the AAA+ ATPase TnsC, the Zn-finger protein TniQ, and the transposase TnsB. Here we present a cryo-electron microscopic structure of a target DNA-bound Cas12k-transposon recruitment complex comprised of RNA-guided Cas12k, TniQ, a polymeric TnsC filament and, unexpectedly, the ribosomal protein S15. Complex assembly, mediated by a network of interactions involving the guide RNA, TniQ, and S15, results in R-loop completion. TniQ contacts two TnsC protomers at the Cas12k-proximal filament end, likely nucleating its polymerization. Transposition activity assays corroborate our structural findings, implying that S15 is a bona fide component of the type V crRNA-guided transposon machinery. Altogether, our work uncovers key mechanistic aspects underpinning RNA-mediated assembly of CRISPR-associated transposons to guide their development as programmable tools for site-specific insertion of large DNA payloads., Competing Interests: Declaration of interests M.S., I.Q., and M.J. are named inventors on a related patent application., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Forearm fractures such as distal radius fractures are traditionally treated with a plaster or synthetic cast. Patients commonly report inconvenience of the cast, skin problems, and occasionally radial sensory nerve numbness. A known issue with casting is that the rate of secondary dislocation is high. As an alternative to casts, personalized 3D-printed braces are increasingly used. This review provides an inventory of current developments and experience with 3D-printed forearm braces. Main focus was on the design requirements, materials used, technical requirements, and preclinical and clinical results. Review of 12 studies showed that all printed braces used an open design. Fused Deposition Modelling is most commonly used 3D-printing technique (seven studies) and polylactic acid is the most commonly used material (five studies). Clinical evaluation was done in six studies, mainly involving distal radius fractures, and generally showed a low complication rate and high patient satisfaction with the printed brace. Whether or not the results obtained with 3D-printed braces are superior to results after casting requires further studies., Competing Interests: Declaration of Competing Interest There are no conflicts of interest to declare for any of the authors involved in this study., (Copyright © 2022 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Aims: The aim of this study was to compare the cost-effectiveness of surgical fixation with Kirschner (K-)wire ersus moulded casting after manipulation of a fracture of the distal radius in an operating theatre setting., Methods: An economic evaluation was conducted based on data collected from the Distal Radius Acute Fracture Fixation Trial 2 (DRAFFT2) multicentre randomized controlled trial in the UK. Resource use was collected at three, six, and 12 months post-randomization using trial case report forms and participant-completed questionnaires. Cost-effectiveness was reported in terms of incremental cost per quality-adjusted life year (QALY) gained from an NHS and personal social services perspective. Sensitivity analyses were conducted to examine the robustness of cost-effectiveness estimates, and decision uncertainty was handled using confidence ellipses and cost-effectiveness acceptability curves., Results: In the base case analysis, surgical fixation with K-wire was more expensive (£29.65 (95% confidence interval (CI) -94.85 to 154.15)) and generated lower QALYs (0.007 (95% CI -0.03 to 0.016)) than moulded casting, but this difference was not statistically significant. The probability of K-wire being cost-effective at a £20,000 per QALY cost-effectiveness threshold was 24%. The cost-effectiveness results remained robust in the sensitivity analyses., Conclusion: The findings suggest that surgical fixation with K-wire is unlikely to be a cost-effective alternative to a moulded cast in adults, following manipulation of a fracture of the distal radius in a theatre setting.Cite this article: Bone Joint J  2022;104-B(11):1225-1233.

Tenderness is one of the main characteristics of meat because it determines its price and acceptability. This is the first bibliometric study on the trend of research on the role of genes in meat tenderness. A total of 175 original and English-language articles published up to 2021 were retrieved from Scopus. The bibliometric analysis was carried out with VOSviewer (version 1.6.18, Eck and Waltman, Leiden, Netherlands) and complemented with the Analyze search results service from Scopus. Erroneous and duplicate data were eliminated, and incomplete information was added to standardize the results. Scientific production was evaluated by means of quantity, quality and structure indicators. As a first glance, 8.816% of authors have published more than 50% of papers mainly related to genes encoding the calpain (CAPN)-calpastatin (CAST) system and single nucleotide polymorphisms (SNPs). Among other findings, a strong link was found between the contribution of the main countries (led by the United States with) and their institutions (led by the USDA Agricultural Research Service with) to their gross domestic product. Most studies on the topic are published in the Journal of Animal Science , and other journals with high impact according to the number of citations and different metrics. Finally, when evaluating the most cited articles, the occurrence and association of the main keywords, it was confirmed that research is focused on the role of CAPN and CAST genes and of SNPs in beef tenderness. The change in science was emphasized; although marker-assisted selection is still used, genes have an infinitesimal effect on complex traits. Therefore, since about 2010, new research groups adopted genomic selection to evaluate dense panels of SNPs and better explain genetic variation in meat tenderness.

Objective: There is limited evidence about the cross-cultural validity of autistic symptoms in school-aged children in Brazil. We used data from a large school survey to evaluate the factor structure of autism symptoms in community-dwelling children and adolescents., Methods: We translated the Childhood Autism Spectrum Test to Brazilian Portuguese and performed factor analyses to investigate the factor structure of parent-reported autistic symptoms in a large sample (n=8,571) of children/adolescents from a school survey in the metropolitan area of São Paulo., Results: Autistic symptoms were best conceptualized under a correlated-factors model with two factors: one predominantly characterized by social-communication symptoms and the other by symptoms of inflexible/restricted language, behaviors, and interests., Conclusions: These findings provide evidence that the structure of autistic symptoms in Brazil is similar to that described in other countries, indicating the cross-cultural validity of autism in Brazil., Competing Interests: EBC has served as consultant, advisory board member, and/or speaker for Aché, Mantecorp, and Takeda. GVP has served as consultant, advisory board member, and/or speaker for Abbott, Aché, Medice, Novo Nordisk, and Takeda; and has received royalties from Editora Manole. The other authors report no conflicts of interest.