Treatment of cryopreserved bovine sperm with calcium ionophore A23187 increases in vitro embryo production.

After ejaculation, mammalian sperm undergo a series of molecular events conducive to the acquisition of fertilizing competence. These events are collectively known as capacitation and involve acrosomal responsiveness and a vigorous sperm motility called hyperactivation. When mimicked in the laboratory, capacitating bovine sperm medium contains bicarbonate, calcium, albumin and heparin, among other components. In this study, we aimed at establishing a new capacitation protocol for bovine sperm, using calcium ionophore. Similar to our findings using mouse sperm, bovine sperm treated with Ca2+ ionophore A23187 were quickly immobilized. However, these sperm initiated capacitation after ionophore removal in fresh medium without heparin, and independent of the Protein Kinase A. When A23187-treated sperm were used on in vitro fertilization (IVF) procedures without heparin, eggs showed cleavage rates similar to standardized IVF protocols using heparin containg synthetic oviduct fluid (IVF-SOF). However, when A23187 pre-treated sperm were further used for inseminating eggs in complete IVF-SOF-heparin, a significantly higher percentage of embryo development was observed, suggesting a synergism between two different signaling pathways during bovine sperm capacitation. These results have the potential to improve current protocols for bovine IVF that could also be applied in other species of commercial interest.

Radiological characterization of the tailings of an abandoned copper mine using a neural network and geostatistical analysis through the Co-Kriging method.

The radiological characterization of soil contaminated with natural radionuclides enables the classification of the area under investigation, the optimization of laboratory measurements, and informed decision-making on potential site remediation. Neural networks (NN) are emerging as a new candidate for performing these tasks as an alternative to conventional geostatistical tools such as Co-Kriging. This study demonstrates the implementation of a NN for estimating radiological values such as ambient dose equivalent (H*(10)), surface activity and activity concentrations of natural radionuclides present in a waste dump of a Cu mine with a high level of natural radionuclides. The results obtained using a NN were compared with those estimated by Co-Kriging. Both models reproduced field measurements equivalently as a function of spatial coordinates. Similarly, the deviations from the reference concentration values obtained in the output layer of the NN were smaller than the deviations obtained from the multiple regression analysis (MRA), as indicated by the results of the root mean square error. Finally, the method validation showed that the estimation of radiological parameters based on their spatial coordinates faithfully reproduced the affected area. The estimation of the activity concentrations was less accurate for both the NN and MRA; however, both methods gave statistically comparable results for activity concentrations obtained by gamma spectrometry (Student's t-test and Fisher's F-test).

Ultrasound-guided cryoablation: Our experience in percutaneous treatment as an alternative to surgery for fibroadenomas of the breast lesions.

OBJECTIVES: To review the tolerance to and medium-term efficacy of ultrasound-guided cryoablation as an alternative to surgical treatment of fibroadenomas of the breast in our hospital. METHODS: We analyzed data from the 12 patients with fibroadenomas treated with ultrasound-guided cryoablation in our hospital between November 2020 and July 2022. Cryoablation was performed with a system using argon gas (Galil Boston Scientific®) or liquid nitrogen (Prosense Ice Cure®) following a triple-phase (freeze-thaw-freeze) protocol of variable duration depending on the size of the lesion. Patients were followed up with ultrasonography at 3, 6, 12, and 18 months. RESULTS: All patients tolerated the procedure well. Two patients reported moderate pain in the hours immediately after the procedure; no other complications occurred. The findings during follow-up included decreased volume of the fibroadenoma (47.07% at 3 months, 77.79% at 6 months, 81.77% at 12 months, and 88.81% at 18 months), blurring of the nodule's margins, a significantly reduced or absent signal within the lesion in the Doppler study, an echogenic band (representing edema, hemorrhage, and fat necrosis), and hypoechoic areas suggestive of fibrosis surrounding the fibroadenoma. CONCLUSIONS: Cryoablation is done on an outpatient basis, avoiding general anesthesia, thus making it less expensive. Cryoablation yields better cosmetic results than surgery.

[Effect of training with immersive virtual reality on the risk of falling in the elderly: a systematic review]. / Efecto del entrenamiento con realidad virtual inmersiva en el riesgo de caída de personas mayores: una revisión sistemática.

Aging entails changes in the human body, generating a decrease in physical capabilities, including the risk of falls. New therapies are currently emerging for the risk of falls and immersive virtual reality is one of them, giving the user a realistic feeling of a virtual environment. This systematic review aims to investigate the effects of immersive virtual reality on the risk of falling in older people. Randomized controlled clinical trials were included, with at least one intervention group that used immersive virtual reality, age >60 years and without multiple serious pathologies. Articles published until November 2023 were included, in accordance with the PRISMA guideline and including the PICO strategy, in the electronic databases PubMed, Scielo, Scopus, Semantic Scholar and Science Direct. From a total of 413 articles, 7 studies were selected, which met the pre-established inclusion and exclusion criteria. Of the studies reviewed, the majority found significant improvements in tests that measure risk of falls, only one study did not find improvements in this variable but did find improvements for walking speed and functional reach test. Despite the limited literature, it seems that these interventions can have a positive effect, becoming a good tool to reduce the risk of falling in older people.

Comparison of water- vs. land-based exercise for improving functional capacity and quality of life in patients living with and beyond breast cancer (the AQUA-FiT study): a randomized controlled trial.

BACKGROUND: Patients living with and beyond breast cancer frequently exhibit several side effects that can impact quality of life and physical functioning way beyond diagnosis and cancer therapies. Traditional on-land exercise has shown to be effective in reducing several symptoms of BC but little is known about the role of water-based exercise in improving physical and psychological well-being. OBJECTIVES: To compare land- vs. water-based exercise training for BC survivors to improve Health-Related Quality of Life (HRQoL), cancer-related fatigue (CRF), physical functioning, body composition and physical activity in patients with BC. METHODS: A randomised, parallel group (1:1) controlled trial was conducted between 2020 and 2022. Patients were randomly allocated to complete a similar exercise training twice weekly during 12 weeks either on land (LG) using traditional gym equipment or in a swimming pool (WG) using body-weight exercises and water-suitable accessories. Both groups were supervised and monitored by an experienced physiotherapist. Main outcome was HRQoL (EORTC QLQ C30 and B23 module) and CRF measured with the Piper Scale. Secondary variables included functional capacity with the 6 Minutes Walking Test (6MWT), upper and lower body strength (handgrip strength and 30″ Sit-to-Stand (STS) test), body composition and objectively measured physical activity. RESULTS: 28 patients were assessed and randomised during the study period. One patient did not receive the allocated intervention due to skin issues and one patient was dropped out during the intervention. A significant effect of time was found for both symptom severity (F(2,52) = 6.46, p = 0.003) and overall functioning (F1.67,43.45 = 5.215, p =0 .013) but no interaction was found between group and time. No effects were reported for CRF. Similar findings were reported for functional capacity (time effect F1.231,32.019 = 16.818, p < 0.001) and lower body strength (time effect F2,52 = 15.120, p < 0.001) as well as fat mass (time effect F2,52 = 4.38, p = 0.017). Notably, a significant time per group interaction was reported for physical activity (F2,52 = 6.349, p =0.003) with patients in the WG significantly improving PA levels over time while patients in the LG exhibited a marked decreased. CONCLUSIONS: Exercise training either in water or on land can decrease symptom severity and improve functionality and body composition. Water-based training seems more effecting than land-based exercise to improve physical activity patterns over time.

Can the Dose of Belimumab be Reduced in Patients with Systemic Lupus Erythematosus?

OBJECTIVES: The aims of this study were to investigate the prevalence of dose reduction in patients with SLE treated with belimumab (BEL) in Spain, analyze treatment modalities, and determine impact on control of disease activity. METHODS: Retrospective longitudinal and multicentre study of SLE patients treated with BEL. Data on disease activity, treatments and outcomes were recorded before and after reduction (6-12 months), and they were compared. RESULTS: A total of 324 patients were included. The dose was reduced in 29 patients (8.9%). The dosing interval was increased in 9 patients receiving subcutaneous BEL and in 6 patients receiving intravenous BEL. The dose per administration was reduced in 16 patients.Pre-reduction status was remission (2021 DORIS) in 15/26 patients (57.7%) and LLDAS in 23/26 patients (88.5%). After reduction, 2/24 patients (8.3%) and 3/22 patients (13.6%) lost remission at 6 months and 12 months, respectively (not statistically significant [NS]). As for LLDAS, 2/23 patients (8.7%) and 2/21 patients (9.5%) lost their status at 6 and 12 months, respectively (NS). Significantly fewer patients were taking glucocorticoids (GCs) at their 12-month visit, although the median dose of GCs was higher at the 12-month visit (5 [0.62-8.75] vs 2.5 [0-5] at baseline). CONCLUSION: Doses of BEL can be reduced with no relevant changes in disease activity-at least in the short term-in a significant percentage of patients, and most maintain the reduced dose. However, increased clinical or serologic activity may be observed in some patients. Consequently, tighter post-reduction follow-up is advisable.

Tryptophan fuels MYC-dependent liver tumorigenesis through indole 3-pyruvate synthesis.

Cancer cells exhibit distinct metabolic activities and nutritional dependencies compared to normal cells. Thus, characterization of nutrient demands by individual tumor types may identify specific vulnerabilities that can be manipulated to target the destruction of cancer cells. We find that MYC-driven liver tumors rely on augmented tryptophan (Trp) uptake, yet Trp utilization to generate metabolites in the kynurenine (Kyn) pathway is reduced. Depriving MYC-driven tumors of Trp through a No-Trp diet not only prevents tumor growth but also restores the transcriptional profile of normal liver cells. Despite Trp starvation, protein synthesis remains unhindered in liver cancer cells. We define a crucial role for the Trp-derived metabolite indole 3-pyruvate (I3P) in liver tumor growth. I3P supplementation effectively restores the growth of liver cancer cells starved of Trp. These findings suggest that I3P is a potential therapeutic target in MYC-driven cancers. Developing methods to target this metabolite represents a potential avenue for liver cancer treatment.

Analysis of the interaction of antimalarial agents with Plasmodium falciparum glutathione reductase through molecular mechanical calculations.

CONTEXT: Malaria remains a significant global health challenge with emerging resistance to current treatments. Plasmodium falciparum glutathione reductase (PfGR) plays a critical role in the defense mechanisms of malaria parasites against oxidative stress. In this study, we investigate the potential of targeting PfGR with conventional antimalarials and dual drugs combining aminoquinoline derivatives with GR inhibitors, which reveal promising interactions between PfGR and studied drugs. The naphthoquinone Atovaquone demonstrated particularly high affinity and potential dual-mode binding with the enzyme active site and cavity. Furthermore, dual drugs exhibit enhanced binding affinity, suggesting their efficacy in inhibiting PfGR, where the aliphatic ester bond (linker) is essential for effective binding with the enzyme's active site. Overall, this research provides important insights into the interactions between antimalarial agents and PfGR and encourages further exploration of its role in the mechanisms of action of antimalarials, including dual drugs, to enhance antiparasitic efficacy. METHODS: The drugs were tested as PfGR potential inhibitors via molecular docking on AutoDock 4, which was performed based on the preoptimized structures in HF/3-21G-PCM level of theory on ORCA 5. Drug-receptor systems with the most promising binding affinities were then studied with a molecular dynamic's simulation on AMBER 16. The molecular dynamics simulations were performed with a 100 ns NPT ensemble employing GAFF2 forcefield in the temperature of 310 K, integration time step of 2 fs, and non-bond cutoff distance of 6.0 Å.

Targeting of neuroblastoma cells through Kynurenine-AHR pathway inhibition.

Neuroblastoma poses significant challenges in clinical management. Despite its relatively low incidence, this malignancy contributes disproportionately to cancer-related childhood mortality. Tailoring treatments based on risk stratification, including MYCN oncogene amplification, remains crucial, yet high-risk cases often confront therapeutic resistance and relapse. Here, we explore the aryl hydrocarbon receptor (AHR), a versatile transcription factor implicated in diverse physiological functions such as xenobiotic response, immune modulation, and cell growth. Despite its varying roles in malignancies, AHR's involvement in neuroblastoma remains elusive. Our study investigates the interplay between AHR and its ligand kynurenine (Kyn) in neuroblastoma cells. Kyn is generated from tryptophan (Trp) by the activity of the enzymes indoleamine 2,3-dioxygenase 1 (IDO1) and tryptophan 2,3-dioxygenase (TDO2). We found that neuroblastoma cells displayed sensitivity to the TDO2 inhibitor 680C91, exposing potential vulnerabilities. Furthermore, combining TDO2 inhibition with retinoic acid or irinotecan (two chemotherapeutic agents used to treat neuroblastoma patients) revealed synergistic effects in select cell lines. Importantly, clinical correlation analysis using patient data established a link between elevated expression of Kyn-AHR pathway genes and adverse prognosis, particularly in older children. These findings underscore the significance of the Kyn-AHR pathway in neuroblastoma progression, emphasizing its potential role as a therapeutic target.

Tratamiento de la pseudoartrosis de radio con injerto de cresta iliaca y células madre del aspirado de médula ósea. A propósito de un caso / Treatment of radial pseudarthrosis with iliac crest graft and bone marrow aspirate stem cells. A case report

La pseudoartrosis es una complicación caracterizada por la ausencia de consolidación del hueso a los 9 meses desde el inicio de la fractura, con falta de progresión radiológica los últimos 3 meses, siendo sus principales causas el exceso de movimiento en el foco de fractura y una insuficiente vascularización. A pesar de no tratarse de una complicación frecuente, los huesos del antebrazo ocupan el 4.º puesto en incidencia de presentación. El manejo anestésico de la patología quirúrgica del miembro superior se realiza generalmente en régimen ambulatorio con técnicas de anestesia regional guiadas por ecografía. Estas técnicas tienen una doble función: anestesia durante el propio acto quirúrgico con una mínima variabilidad sobre el estado basal del paciente y analgesia en el postoperatorio inmediato, permitiendo de esta manera el alta a domicilio de forma más segura y precoz. Presentamos el caso de un varón de 34 años, con desarrollo de pseudoartrosis atrófica tras fractura diafisaria de radio, en el que se realiza injerto óseo de cresta ilíaca y aspirado de células madre como estímulo de la osteogénesis.(AU)

Pseudarthrosis is a complication characterised by the absence of bone healing 9 months after the onset of the fracture, with a lack of radiological progressionin the last 3 months, and its main causes are excessive movement at the fracture site and insufficient vascularisation. Despite not being a frequent complica-tion, the bones of the forearm occupy the fourth place in incidence of presentation. The anaesthetic management of surgical pathology of the upper limb isgenerally performed on an outpatient basis with regional anaesthesia techniques guided by ultrasound. These techniques have a dual function: anaesthesiaduring the surgical act with minimal variability over the patient’s baseline condition and analgesia in the immediate postoperative period, thus allowing forsafer and earlier discharge home. We present the case of a 34-year-old male with diagnosis of atrophic pseudarthrosis following a diaphyseal fracture of theradius, in whom iliac crest bone grafting and stem cell aspiration were performed to stimulate osteogenesis.(AU)

ZNF692 regulates nucleolar morphology by interacting with NPM1 and modifying its self-assembly properties.

The nucleolus, a membrane-less organelle, is responsible for ribosomal RNA transcription, ribosomal RNA processing, and ribosome assembly. Nucleolar size and number are indicative of a cell's protein synthesis rate and proliferative capacity, and abnormalities in the nucleolus have been linked to neurodegenerative diseases and cancer. In this study, we demonstrated that the nucleolar protein ZNF692 directly interacts with nucleophosmin 1 (NPM1). Knocking down ZNF692 resulted in the nucleolar redistribution of NPM1 in ring-like structures and reduced protein synthesis. Purified NPM1 forms spherical condensates in vitro but mixing it with ZNF692 produces irregular condensates more closely resembling living cell nucleoli. Our findings indicate that ZNF692, by interacting with NPM1, plays a critical role in regulating nucleolar architecture and function in living cells.

Colgajo nautilus y colgajo en muleta taurina para defectos quirúrgicos faciales periorificiales / Nautilus Flap and Bullfighter Crutch Flap for the Repair of Periorificial Surgical Defects of the Face

Antecedentes La reconstrucción de defectos quirúrgicos en regiones anatómicas próximas a bordes palpebrales, fosas nasales o boca es un reto debido su tendencia a ser deformadas por la tensión del cierre directo o los colgajos cutáneos. El empleo de nuevas técnicas reconstructivas que eviten la retracción de estas zonas sensibles puede suponer un avance importante. Pacientes y métodos Se emplean 2 nuevos diseños, el colgajo nautilus y el colgajo en muleta taurina, para la reconstrucción de defectos quirúrgicos periorificiales, realizando una recolección retrospectiva de los mismos en las zonas periparpebral, perivestibular nasal y peribucal. El colgajo nautilus se empleó en 4 pacientes con defectos periparpebrales y 2 peribucales. El colgajo en muleta taurina se utilizó para la reconstrucción de 14 defectos en ala nasal. Resultados En los 20 pacientes se obtuvieron resultados muy satisfactorios tanto a nivel estético como funcional, sin la aparición de ectropión, colapso del vestíbulo nasal o asimetría de borde labial. No se observó necrosis en ningún caso. Conclusiones Proponemos el colgajo nautilus y el colgajo en muleta taurina como una excelente opción reconstructiva para defectos quirúrgicos localizados en zonas periorificiales (AU)

Background Reconstruction of surgical defects located close to eyelid edges, nostrils, or the mouth is challenging, as tension generated by direct closure or skin flaps in these sensitive regions tends to cause distortion. New repair techniques that prevent retraction may significantly improve outcomes. Patients and methods Retrospective study of the use of 2 novel flap designs—the nautilus flap and the bullfighter crutch flap—to repair surgical defects in the peripalpebral, perivestibular, nasal, and perioral areas. The nautilus flap was used to repair 4 peripalpebral defects and 2 perioral defects, and the bullfighter crutch flap to repair 14 nasal ala defects.Results Cosmetic and functional outcomes were very satisfactory in all 20 patients, with no cases of ectropion, nasal vestibule collapse, or labial asymmetry. Necrosis did not occur in any of the cases. Conclusions The nautilus and bullfighter crutch flaps appear to be excellent choices for reconstructing surgical defects in periorificial areas (AU)

[Translated article] Nautilus Flap and Bullfighter Crutch Flap for the Repair of Periorificial Surgical Defects of the Face / Colgajo nautilus y colgajo en muleta taurina para defectos quirúrgicos faciales periorificiales

Background Reconstruction of surgical defects located close to eyelid edges, nostrils, or the mouth is challenging, as tension generated by direct closure or skin flaps in these sensitive regions tends to cause distortion. New repair techniques that prevent retraction may significantly improve outcomes. Patients and methods Retrospective study of the use of 2 novel flap designs—the nautilus flap and the bullfighter crutch flap—to repair surgical defects in the peripalpebral, perivestibular, nasal, and perioral areas. The nautilus flap was used to repair 4 peripalpebral defects and 2 perioral defects, and the bullfighter crutch flap to repair 14 nasal ala defects.Results Cosmetic and functional outcomes were very satisfactory in all 20 patients, with no cases of ectropion, nasal vestibule collapse, or labial asymmetry. Necrosis did not occur in any of the cases. Conclusions The nautilus and bullfighter crutch flaps appear to be excellent choices for reconstructing surgical defects in periorificial areas (AU)

Antecedentes La reconstrucción de defectos quirúrgicos en regiones anatómicas próximas a bordes palpebrales, fosas nasales o boca es un reto debido su tendencia a ser deformadas por la tensión del cierre directo o los colgajos cutáneos. El empleo de nuevas técnicas reconstructivas que eviten la retracción de estas zonas sensibles puede suponer un avance importante. Pacientes y métodos Se emplean 2 nuevos diseños, el colgajo nautilus y el colgajo en muleta taurina, para la reconstrucción de defectos quirúrgicos periorificiales, realizando una recolección retrospectiva de los mismos en las zonas periparpebral, perivestibular nasal y peribucal. El colgajo nautilus se empleó en 4 pacientes con defectos periparpebrales y 2 peribucales. El colgajo en muleta taurina se utilizó para la reconstrucción de 14 defectos en ala nasal. Resultados En los 20 pacientes se obtuvieron resultados muy satisfactorios tanto a nivel estético como funcional, sin la aparición de ectropión, colapso del vestíbulo nasal o asimetría de borde labial. No se observó necrosis en ningún caso. Conclusiones Proponemos el colgajo nautilus y el colgajo en muleta taurina como una excelente opción reconstructiva para defectos quirúrgicos localizados en zonas periorificiales (AU)

Which information derived from the Coma Recovery Scale-Revised provides the most reliable prediction of clinical diagnosis and recovery of consciousness? A comparative study using machine learning techniques.

BACKGROUND: The Coma Recovery Scale-Revised (CRS-R) is the most recommended clinical tool to examine the neurobehavioral condition of individuals with disorders of consciousness (DOCs). Different studies have investigated the prognostic value of the information provided by the conventional administration of the scale, while other measures derived from the scale have been proposed to improve the prognosis of DOCs. However, the heterogeneity of the data used in the different studies prevents a reliable comparison of the identified predictors and measures. AIM: This study investigates which information derived from the CRS-R provides the most reliable prediction of both the clinical diagnosis and recovery of consciousness at the discharge of a long-term neurorehabilitation program. DESIGN: Retrospective observational multisite study. SETTING: The enrollment was performed in three neurorehabilitation facilities of the same hospital network. POPULATION: A total of 171 individuals with DOCs admitted to an inpatient neurorehabilitation program for a minimum of 3 months were enrolled. METHODS: Machine learning classifiers were trained to predict the clinical diagnosis and recovery of consciousness at discharge using clinical confounders and different metrics extracted from the CRS-R scale. RESULTS: Results showed that the neurobehavioral state at discharge was predicted with acceptable and comparable predictive value with all the indices and measures derived from the CRS-R, but for the clinical diagnosis and the Consciousness Domain Index, and the recovery of consciousness was predicted with higher accuracy and similarly by all the investigated measures, with the exception of initial clinical diagnosis. CONCLUSIONS: Interestingly, the total score in the CRS-R and, especially, the total score in its subscales provided the best overall results, in contrast to the clinical diagnosis, which could indicate that a comprehensive measure of the clinical diagnosis rather than the condition of the individuals could provide a more reliable prediction of the neurobehavioral progress of individuals with prolonged DOC. CLINICAL REHABILITATION IMPACT: The results of this work have important implications in clinical practice, offering a more accurate prognosis of patients and thus giving the possibility to personalize and optimize the rehabilitation plan of patients with DoC using low-cost and easily collectable information.

Efficacy and safety of an early oral switch in low-risk Staphylococcus aureus bloodstream infection (SABATO): an international, open-label, parallel-group, randomised, controlled, non-inferiority trial.

BACKGROUND: Staphylococcus aureus bloodstream infection is treated with at least 14 days of intravenous antimicrobials. We assessed the efficacy and safety of an early switch to oral therapy in patients at low risk for complications related to S aureus bloodstream infection. METHODS: In this international, open-label, randomised, controlled, non-inferiority trial done in 31 tertiary care hospitals in Germany, France, the Netherlands, and Spain, adult patients with low-risk S aureus bloodstream infection were randomly assigned after 5-7 days of intravenous antimicrobial therapy to oral antimicrobial therapy or to continue intravenous standard therapy. Randomisation was done via a central web-based system, using permuted blocks of varying length, and stratified by study centre. The main exclusion criteria were signs and symptoms of complicated S aureus bloodstream infection, non-removable foreign devices, and severe comorbidity. The composite primary endpoint was the occurrence of any complication related to S aureus bloodstream infection (relapsing S aureus bloodstream infection, deep-seated infection, and mortality attributable to infection) within 90 days, assessed in the intention-to-treat population by clinical assessors who were masked to treatment assignment. Adverse events were assessed in all participants who received at least one dose of study medication (safety population). Due to slow recruitment, the scientific advisory committee decided on Jan 15, 2018, to stop the trial after 215 participants were randomly assigned (planned sample size was 430 participants) and to convert the planned interim analysis into the final analysis. The decision was taken without knowledge of outcome data, at a time when 126 participants were enrolled. The new sample size accommodated a non-inferiority margin of 10%; to claim non-inferiority, the upper bound of the 95% CI for the treatment difference (stratified by centre) had to be below 10 percentage points. The trial is closed to recruitment and is registered with ClinicalTrials.gov (NCT01792804), the German Clinical trials register (DRKS00004741), and EudraCT (2013-000577-77). FINDINGS: Of 5063 patients with S aureus bloodstream infection assessed for eligibility, 213 were randomly assigned to switch to oral therapy (n=108) or to continue intravenous therapy (n=105). Mean age was 63·5 (SD 17·2) years and 148 (69%) participants were male and 65 (31%) were female. In the oral switch group, 14 (13%) participants met the primary endpoint versus 13 (12%) in the intravenous group, with a treatment difference of 0·7 percentage points (95% CI -7·8 to 9·1; p=0·013). In the oral switch group, 36 (34%) of 107 participants in the safety population had at least one serious adverse event compared with 27 (26%) of 103 participants in the intravenous group (p=0·29). INTERPRETATION: Oral switch antimicrobial therapy was non-inferior to intravenous standard therapy in participants with low-risk S aureus bloodstream infection. However, it is necessary to carefully assess patients for signs and symptoms of complicated S aureus bloodstream infection at the time of presentation and thereafter before considering early oral switch therapy. FUNDING: Deutsche Forschungsgemeinschaft. TRANSLATIONS: For the German, Spanish, French and Dutch translations of the abstract see Supplementary Materials section.

[Translated article] Nautilus Flap and Bullfighter Crutch Flap for the Repair of Periorificial Surgical Defects of the Face.

BACKGROUND: Reconstruction of surgical defects located close to eyelid edges, nostrils, or the mouth is challenging, as tension generated by direct closure or skin flaps in these sensitive regions tends to cause distortion. New repair techniques that prevent retraction may significantly improve outcomes. PATIENTS AND METHODS: Retrospective study of the use of 2 novel flap designs-the nautilus flap and the bullfighter crutch flap-to repair surgical defects in the peripalpebral, perivestibular, nasal, and perioral areas. The nautilus flap was used to repair 4 peripalpebral defects and 2 perioral defects, and the bullfighter crutch flap to repair 14 nasal ala defects. RESULTS: Cosmetic and functional outcomes were very satisfactory in all 20 patients, with no cases of ectropion, nasal vestibule collapse, or labial asymmetry. Necrosis did not occur in any of the cases. CONCLUSIONS: The nautilus and bullfighter crutch flaps appear to be excellent choices for reconstructing surgical defects in periorificial areas.