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Mutations in the RYR1 gene, responsible for encoding the skeletal muscle calcium release channel, are linked to conditions such as malignant hyperthermia and central core disease. These mutations can severely affect calcium handling and excitation-contraction coupling, leading to different clinical manifestations including muscle fiber abnormalities. We present two siblings diagnosed with congenital myopathy due to a homozygous variant c.14,928 C > G (p.Phe4976Leu) in the RYR1 gene, inherited in an autosomal recessive pattern. Both twins, born prematurely via cesarean section, exhibited hypotonia and arthrogryposis. Clinical exome sequencing confirmed the RYR1 mutation, and an antioxidant supplement, idebenone, was introduced. Despite sharing the same variant, the twins presented discordant clinical phenotypes with varying degrees of muscle impairment and other complications. This case highlights the critical role of epigenetic in modulating disease expression, suggesting personalized therapeutic strategies are paramount even in siblings sharing the same homozygous variant.

To assess whether Neuroglobin could play a functional role during perinatal period and birth, it was analyzed in 83 umbilical cord blood samples where its concentration ranged between 1.65 and 45.18 ng/mL, mean 18.49 ng/mL. Although resembling concentrations previously detected in many pathologic conditions in adults, none of newborns displayed altered Apgar score and were regularly discharged in healthy status. Surprisingly, 83.13% of babies had NGB concentrations higher than the putative 8.4 ng/mL value, recently hypothesized as a prognostic cut-off between good and bad recovery from cerebral ischemia in adults. Significant Pearson correlations were observed between NGB and Hb ( r  = 0.368, p  = 0.001), and Htc ( r  = 0.372, p  = 0.001) confirming its physiological role in oxygen-regulated metabolic information within the child-mother dyad. Besides the direct action in regulating blood flow and gas exchange, the first NGB discovery in cord blood is discussed in relation to new perspectives in perinatal medicine.

Here, we performed a systematic DFT study assisted by the workflow framework SimStack for the mechanical and thermodynamic properties of the clay mineral lizardite in pristine and six different types of O vacancies configurations. In most cases, the defect caused a structural phase transition in the lizardite from the trigonal (pristine) to the triclinic phase. The results show that oxygen vacancies in lizardite significantly reduce the lattice thermal conductivity, accompanied by an elastic moduli reduction and an anisotropy index increase. Through the P–V relation, an increase in compressibility was evidenced for vacancy configurations. Except for the vacancy with the same crystalline structure as pristine lizardite, the sound velocities of the other vacancy configurations produce a decrease in these velocities, and it is essential to highlight high values for the Grüneisen parameter. We emphasize the great relevance of the punctual-defects introduction, such as O vacancies, in lizardite, since this microstructural design is responsible for the decrease of the lattice thermal conductivity in comparison with the pristine system by decreasing the heat transfer ability, turning lizardite into a promising candidate for thermoelectric materials

Background:Secukinumab is a human monoclonal antibody that selectively binds interleukin 17A, inhibiting its interaction with the interleukin 17 receptor and is prescribed for the treatment of psoriatic arthritis (PsA), plaque psoriasis, ankylosing spondylitis, axial spondyloarthritis, and juvenile idiopathic arthritis.Objectives:To retrospectively evaluate the drug retention rate (DRR) of secukinumab in a monocentric cohort of patients affected by spondyloarthritis.Methods:Patients with a diagnosis of spondyloarthritis and treated with secukinumab who were evaluated at our outpatient clinic from January 2017 to February 2023 were included in the study. Demographic, clinical characteristics, and comorbidities were recorded. DRR was evaluated by Kaplan-Meier method as time to drug discontinuation, and baseline factors predicting drug discontinuation were investigated through Cox regression after adjusting for baseline confounders.Results:One-hundred-seventy-eight patients were included in the study, with a median follow-up of 20.5 (IQR 10-39) months. Among these, 64.6% of patients were female, and 9.7% tested positive for HLAB27. 69.7% of patients presented peripheral involvement, 52.2% axial involvement, 40.4% enthesitis, and 52% psoriasis. Comorbidities were observed in 65.2% of patients, with the most common being hypertension (34.8%), cardiovascular diseases (18.5%), hepatic steatosis (22.5%), diabetes (11.8%), hyperlipemia (23%), kidney disease (6.2%), and a personal history of cancer (10.1%). The multivariable analysis identified the number of previous targeted synthetic or biological DMARD (ts/b DMARDs) (HR 1.44, 95% CI 1.01-2.06), hypertension at baseline (HR 2.56, 95% CI 1.08-6.11), and body mass index (BMI) (HR 1.08, 95% CI 1.01-1.17) as independent predictors of drug discontinuation. In contrast, old age at diagnosis was associated with a lower risk of discontinuation (HR 0.96, 95% CI 0.92-0.99) (Table 1). The drug retention rate at 12, 24 and 48 months was 79.4%, 69.3%, 55% respectively (Figure 1, panels A and B).Conclusion:In our cohort, secukinumab revealed a good DRR. An old age at diagnosis seemed to be protective against withdrawal, whereas the number of previous ts/b DMARDs, hypertension at baseline, and BMI were identified as predictors of drug discontinuation. Further studies are needed to confirm our findings.Table 1.Predictors of secukinumab withdrawal (Cox regression)VariableHR (95%CI)P valueNumber of previous ts/b DMARDs1.44 (1.01-2.06)0.045Hypertension2.56 (1.08-6.11)0.033BMI1.08 (1.01-1.17)0.036Age at diagnosis0.96 (0.92-0.99)0.038Variables in the model: gender, age at diagnosis, BMI, disease duration before secukinumab, number of previous ts/b DMARDs, psoriasis, SPA phenotype.Figure 1.Secukinumab retention rate.REFERENCES:NIL.Acknowledgements:NIL.Disclosure of Interests:Elisa Bellis BMS, Mariele Gatto GSK, Astrazeneca, Janssen, GSK, Denise Donzella Janssen, Gloria Crepaldi Janssen, Galapagos, Eli Lilly, BMS, Novartis, Abbvie, Alfasigma, Valeria Data: None declared, Silvia Di Gregorio: None declared, Marinella Gammino: None declared, Valeria Guardo: None declared, Claudia Lomater Abbvie, BMS, Janssen, Eli Lilly, Novartis, Pfizer, Gaetano Liperoti: None declared, Elena Marucco: None declared, Ginevra Pastorin: None declared, Silvia Perrone: None declared, Marta Saracco: None declared, Annamaria Iagnocco Abbvie, Alfasigma, BMS, Celgene, Celltrion, Eli Lilly, Galapagos, Gilead, Janssen, MSD, Novartis, Pfizer, Sanofy Genzyme, SOBI, Abbvie, Pfizer, Novartis.

Injuries to the anterior cruciate ligament (ACL) are currently treated with replacement of the torn ligament with a graft of tendon harvested from elsewhere in the knee. This procedure, called “ACL reconstruction,” is excellent for restoring gross stability to the knee; however, there are relatively high graft failure rates in adolescent patients (Barber et al. in Arthroscopy 30(4):483–491, 2014 ; Engelman et al. in Am J Sports Med, 2014 ; Webster et al. in Am J Sports Med 42(3):641–647, 2014 ), and the ACL reconstruction procedure does not prevent the premature osteoarthritis seen in patients after an ACL injury (Ajuied et al. in Am J Sports Med, 2013 ; Song et al. in J Sports Med 41(10):2340–2346, 2013 ; Tourville et al. Am J Sports Med 41(4):769–778, 2013 ) .Thus, new solutions are needed for ACL injuries. Researchers have been investigating the use of scaffolds, growth factors and cells to supplement a suture repair of the ACL (bridge-enhanced repair; also called bio-enhanced repair in prior publications). In this paper, we will review the varied approaches which have been investigated for stimulating ACL healing and repair in preclinical models and how one of these technologies was able to move from promising preclinical results to FDA acceptance of an investigational device exemption application for a first-in-human study.

Background: Bridge-enhanced anterior cruciate ligament repair (BEAR) combines suture repair of the anterior cruciate ligament (ACL) with a specific extracellular matrix scaffold (the BEAR scaffold) that is placed in the gap between the torn ends of the ACL to facilitate ligament healing. Purpose/Hypothesis: The purpose of this study was to report the 12- and 24-month outcomes of patients who underwent the BEAR procedure compared with a nonrandomized concurrent control group who underwent ACL reconstruction (ACLR) with an autograft. We hypothesized that the BEAR group would have physical examination findings, patient-reported outcomes, and adverse events that were similar to those of the ACLR group. Study Design: Cohort study; Level of evidence, 2. Methods: Ten patients underwent BEAR, and 10 underwent ACLR with a 4-stranded hamstring autograft. At 24 months, 9 of the 10 BEAR patients and 7 of the 10 ACLR patients completed a study visit. Outcomes reported included International Knee Documentation Committee (IKDC) subjective and objective results, knee anteroposterior (AP) laxity findings via an arthrometer, and functional outcomes. Results: There were no graft or repair failures in the first 24 months after surgery. The IKDC subjective scores in both groups improved significantly from baseline (P < .0001) at 12 and 24 months, to 84.6 ± 17.2 in the ACLR group and to 91.7 ± 11.7 in the BEAR group. An IKDC objective grade of A (normal) was found in 44% of patients in the BEAR group and in 29% of patients in the ACLR group at 24 months; no patients in either group had C (abnormal) or D (severely abnormal) grades. Arthrometer testing demonstrated mean side-to-side differences in AP laxity that were similar in the 2 groups at 24 months (BEAR, 1.94 ± 2.08 mm; ACLR, 3.14 ± 2.66 mm). Functional hop testing results were similar in the 2 groups at 12 and 24 months after surgery. Hamstring strength indices were significantly higher in the BEAR group compared with the ACLR group (P = .0001). Conclusion: In this small, first-in-human study, BEAR produced similar outcomes to ACLR with a hamstring autograft. BEAR may result in knee stability and patient-reported outcomes at 2 years sufficient to warrant longer term studies of efficacy in larger groups of patients.

Objectives. To test the hypothesis that neonatal supplementation with lutein in the first hours of life reduces neonatal oxidative stress (OS) in the immediate postpartum period. Methods. A randomized controlled, double-blinded clinical trial was conducted among 150 newborns divided into control group, not supplemented (n=47), and test group, supplemented with lutein on the first day postpartum (n=103). Blood Samples were collected at birth from cord and at 48 hrs postpartum while routine neonatal metabolic screenings were taking place. Total hydroperoxide (TH), advanced oxidation protein products (AOPP), and biological antioxidant potential (BAP) were measured by spectrophotometry and data were analyzed by Wilcoxon rank sum test and by multivariate logistic regression analysis. Results. Before lutein supplementation, the mean blood concentrations of AOPP, TH, and BAP were 36.10 umol/L, 156.75 mmol/H2O2, and 2361.04 umol/L in the test group. After lutein supplementation, significantly higher BAP increment (0.17 ± 0.22 versus 0.06 versus ± 0.46) and lower TH increment (0.46 ± 0.54 versus 0.34 ± 0.52) were observed in the test group compared to controls. Conclusion. Neonatal supplementation with lutein in the first hours of life increases BAP and reduces TH in supplemented babies compared to those untreated. The generation of free radical-induced damage at birth is reduced by lutein. This trial is registered with ClinicalTrials.gov NCT02068807.

This research paper aims to investigate if oxidative stress biomarkers increase after a painful procedure in term newborns and if nonpharmacological approaches, or sex, influence pain degree, and the subsequent OS. 83 healthy term newborns were enrolled to receive 10% oral glucose or sensorial saturation (SS) for analgesia during heel prick (HP). The ABC scale was used to score the pain. Advanced oxidation protein products (AOPP) and total hydroperoxides (TH) as biomarkers of OS were measured at the beginning (early-sample) and at the end (late-sample) of HP. The early-sample/late-sample ratio for AOPP and TH was used to evaluate the increase in OS biomarkers after HP. Higher levels of both AOPP and TH ratio were observed in high degree pain (4–6) compared with low degree pain score (0–3) (AOPP: p=0.049; TH: p=0.001). Newborns receiving SS showed a significantly lower pain score (p=0.000) and AOPP ratio levels (p=0.021) than those without. Males showed higher TH levels at the end of HP (p=0.005) compared to females. The current study demonstrates that a relationship between pain degree and OS exists in healthy full-term newborns. The amount of OS is gender related, being higher in males. SS reduces pain score together with pain-related OS in the newborns.

To test the hypothesis that oral administration of 24% sucrose associated with nonnutritive sucking in healthy newborns receiving venipuncture beyond the first week of life controls pain and pain-related variation in heart rate (HR) and noninvasive oxygen saturation (SpO ). A total of 66 term newborns were enrolled between February and September 2017 in the Neonatology Department of AORN Santobono-Pausilipon, Naples. They were randomly assigned to receive oral 1 mL 24% sucrose (treated group [TG], n=33; gestational age 38.53±1.49 weeks; body weight 3,035±55 g; age 22.40±6.82 weeks) or oral 1 mL 10% glucose (control group [CG], n=33; gestational age 38.91±1.45 weeks; body weight 3,203±65 g; age 23.36±7.02 weeks) 1 minute before and during venipuncture. Evaluations were carried out between 8 and 9 am in all newborns. The Neonatal Infant Pain Scale (NIPS) was used to assess pain in newborns. Outcome measurements (HR, SpO ) were obtained before (T0), during (T1), and 1 minute after (T2) venipuncture using a Nellcor bedside SpO patient-monitoring system. NIPS scores were recorded throughout the procedure. Statistical analysis was performed using SPSS version 20.0. Changes in HR and SpO were assessed by mixed ANOVA for repeated measures. NIPS scores were evaluated by Mann-Whitney test. There were no statistically significant differences in HR or SpO between TG and CG at T0. HR was significantly lower in TG than CG at both T1 and T2 ( <0.05), whereas SpO was significantly higher in TG than CG at both T1 and T2 ( <0.05). NIPS scores were significantly lower in TG (median 0) than CG (median 6) during the entire procedure ( <0.05). Oral administration of 24% sucrose associated with nonnutritive sucking prior to and during a painful procedure has a strong impact on pain response in term newborns, reducing NIPS scores and influencing pain-associated variations in HR and SpO . Complete analgesia during painful procedures in term newborns might prevent pain reactivity and its behavioral and neurodevelopmental consequences. Replication of this study is needed before widespread application of findings.

Metallic fixation systems are currently the gold standard for fracture fixation but have problems including stress shielding, palpability and temperature sensitivity. Recently, resorbable systems have gained interest because they avoid removal and may improve bone remodelling due to the lack of stress shielding. However, their use is limited to paediatric craniofacial procedures mainly due to the laborious implantation requirements. Here we prepare and characterize a new family of resorbable screws prepared from silk fibroin for craniofacial fracture repair. In vivo assessment in rat femurs shows the screws to be self-tapping, remain fixed in the bone for 4 and 8 weeks, exhibit biocompatibility and promote bone remodelling. The silk-based devices compare favourably with current poly-lactic- co -glycolic acid fixation systems, however, silk-based devices offer numerous advantages including ease of implantation, conformal fit to the repair site, sterilization by autoclaving and minimal inflammatory response. Current bone fracture repair options include metallic and resorbable systems, both of which suffer from various issues and limitations. Here, the authors demonstrate resorbable and biocompatible silk bone screws, via in vivo testing.