H2 inhalation therapy in patients with moderate COVID-19 (H2COVID): a prospective ascending-dose phase I clinical trial.

The coronavirus disease 2019 (COVID-19) pandemic, caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has triggered a serious global health crisis, resulting in millions of reported deaths since its initial identification in China in November 2019. The global disparities in immunization access emphasize the urgent need for ongoing research into therapeutic interventions. This study focuses on the potential use of molecular dihydrogen (H2) inhalation as an adjunctive treatment for COVID-19. H2 therapy shows promise in inhibiting intracellular signaling pathways associated with inflammation, particularly when administered early in conjunction with nasal oxygen therapy. This phase I study, characterized by an open-label, prospective, monocentric, and single ascending-dose design, seeks to assess the safety and tolerability of the procedure in individuals with confirmed SARS-CoV-2 infection. Employing a 3 + 3 design, the study includes three exposure durations (target durations): 1 day (D1), 3 days (D2), and 6 days (D3). We concluded that the maximum tolerated duration is at least 3 days. Every patient showed clinical improvement and excellent tolerance to H2 therapy. To the best of our knowledge, this phase I clinical trial is the first to establish the safety of inhaling a mixture of H2 (3.6%) and N2 (96.4%) in hospitalized COVID-19 patients. The original device and method employed ensure the absence of explosion risk. The encouraging outcomes observed in the 12 patients included in the study justify further exploration through larger, controlled clinical trials. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as NCT04633980.

Luxaciones periastragalinas: análisis de una serie de casos. Nuestro algoritmo de tratamiento urgente / Subtalar dislocations: Analysis of a case series. Our urgent treatment algorithm

Introducción y objetivos: Las luxaciones periastragalinas son una entidad poco frecuente (<1%) de las lesiones traumáticas del pie. Se produce una pérdida de relación anatómica entre astrágalo, calcáneo y escafoides. Solo hay pequeñas series publicadas. Material y métodos: Presentamos los casos de una serie de pacientes (N=13) con luxaciones periastragalinas en los que se realizó un análisis descriptivo de las principales variables epidemiológicas, clínicas y radiológicas, a partir de las cuales se propone un algoritmo de tratamiento urgente. Se excluyeron los casos con fracturas del cuello del astrágalo, cuerpo del calcáneo o fracturas-luxación de Chopart aisladas. Resultados: La mediana de edad fue de 48,5 años con predominio del sexo masculino (69,23%). Cinco pacientes sufrieron caídas-entorsis sobre el tobillo y los 8 restantes mecanismos de alta energía. Las luxaciones mediales (9) predominaron sobre las laterales (4). Además, 4 pacientes presentaron luxaciones abiertas, 2 de ellas tipo IIIC que precisaron amputación. Se solicitó TC en un 76,93% de pacientes y 10 presentaron lesiones óseas asociadas del pie. Se realizó cirugía mediante reducción abierta en todas las lesiones abiertas y en un caso en el que fracasó la reducción cerrada. Cinco pacientes precisaron fijador externo tipo delta. Se objetivó esclerosis subcondral articular en un 77,77% de los casos; si bien solo uno precisó artrodesis subtalar. Conclusiones: Las luxaciones periastragalinas son una urgencia traumatológica y precisan una reducción precoz e inmovilización posterior. La fijación externa temporal transarticular es una buena opción de inmovilización en luxaciones abiertas. Son lesiones graves con alta probabilidad de artrosis precoz.(AU)

Introduction and objectives: Subtalar dislocations are a rare entity (<1%) in traumatic foot injuries. There is a loss of anatomical relationship between the talus, calcaneus and scaphoid. There are only small-published series. Material and methods: We present a series of patients (N=13) with subtalar dislocations in which a descriptive analysis of the main epidemiological, clinical and radiological variables was carried out, from which an urgent treatment algorithm is proposed. Cases with fractures of the neck of the talus, body of the calcaneus, or isolated Chopart fracture-dislocations were excluded. Results: The median age was 48.5 years with a predominance of males (69.23%). Five patients suffered falls or sprained ankles and the other eight suffered high-energy mechanisms. The medial dislocations (nine) predominated over the lateral ones (four). In addition, four patients presented open dislocations, two of them type IIIC that required amputation. CT scans were requested in 76.93% of patients and 10 presented associated bone lesions of the foot. Open reduction surgery was performed in all open lesions and in one case in which closed reduction failed. Five patients required a delta-type external fixator. Subchondral articular sclerosis was observed in 77.77% of cases; although only one required subtalar arthrodesis. Conclusions: Subtalar dislocations are a traumatic emergency that require early reduction and subsequent immobilization. Transarticular temporary external fixation is a good immobilization option in open dislocations. They are serious lesions with a high probability of early osteoarthritis.(AU)

[Translated article] Subtalar dislocations: Analysis of a case series. Our urgent treatment algorithm / Luxaciones periastragalinas: análisis de una serie de casos. Nuestro algoritmo de tratamiento urgente

Introducción y objetivos: Las luxaciones periastragalinas son una entidad poco frecuente (<1%) de las lesiones traumáticas del pie. Se produce una pérdida de relación anatómica entre astrágalo, calcáneo y escafoides. Solo hay pequeñas series publicadas. Material y métodos: Presentamos los casos de una serie de pacientes (N=13) con luxaciones periastragalinas en los que se realizó un análisis descriptivo de las principales variables epidemiológicas, clínicas y radiológicas, a partir de las cuales se propone un algoritmo de tratamiento urgente. Se excluyeron los casos con fracturas del cuello del astrágalo, cuerpo del calcáneo o fracturas-luxación de Chopart aisladas. Resultados: La mediana de edad fue de 48,5 años con predominio del sexo masculino (69,23%). Cinco pacientes sufrieron caídas-entorsis sobre el tobillo y los 8 restantes mecanismos de alta energía. Las luxaciones mediales (9) predominaron sobre las laterales (4). Además, 4 pacientes presentaron luxaciones abiertas, 2 de ellas tipo IIIC que precisaron amputación. Se solicitó TC en un 76,93% de pacientes y 10 presentaron lesiones óseas asociadas del pie. Se realizó cirugía mediante reducción abierta en todas las lesiones abiertas y en un caso en el que fracasó la reducción cerrada. Cinco pacientes precisaron fijador externo tipo delta. Se objetivó esclerosis subcondral articular en un 77,77% de los casos; si bien solo uno precisó artrodesis subtalar. Conclusiones: Las luxaciones periastragalinas son una urgencia traumatológica y precisan una reducción precoz e inmovilización posterior. La fijación externa temporal transarticular es una buena opción de inmovilización en luxaciones abiertas. Son lesiones graves con alta probabilidad de artrosis precoz.(AU)

Introduction and objectives: Subtalar dislocations are a rare entity (<1%) in traumatic foot injuries. There is a loss of anatomical relationship between the talus, calcaneus and scaphoid. There are only small-published series. Material and methods: We present a series of patients (N=13) with subtalar dislocations in which a descriptive analysis of the main epidemiological, clinical and radiological variables was carried out, from which an urgent treatment algorithm is proposed. Cases with fractures of the neck of the talus, body of the calcaneus, or isolated Chopart fracture-dislocations were excluded. Results: The median age was 48.5 years with a predominance of males (69.23%). Five patients suffered falls or sprained ankles and the other eight suffered high-energy mechanisms. The medial dislocations (nine) predominated over the lateral ones (four). In addition, four patients presented open dislocations, two of them type IIIC that required amputation. CT scans were requested in 76.93% of patients and 10 presented associated bone lesions of the foot. Open reduction surgery was performed in all open lesions and in one case in which closed reduction failed. Five patients required a delta-type external fixator. Subchondral articular sclerosis was observed in 77.77% of cases; although only one required subtalar arthrodesis. Conclusions: Subtalar dislocations are a traumatic emergency that require early reduction and subsequent immobilization. Transarticular temporary external fixation is a good immobilization option in open dislocations. They are serious lesions with a high probability of early osteoarthritis.(AU)

[Translated article] SCIWORA in children. A rare clinical entity: Ambispective study / SCIWORA. Una rara entidad clínica en la población pediátrica. Estudio ambispectivo

Introducción y objetivos: Las luxaciones periastragalinas son una entidad poco frecuente (<1%) de las lesiones traumáticas del pie. Se produce una pérdida de relación anatómica entre astrágalo, calcáneo y escafoides. Solo hay pequeñas series publicadas. Material y métodos: Presentamos los casos de una serie de pacientes (N=13) con luxaciones periastragalinas en los que se realizó un análisis descriptivo de las principales variables epidemiológicas, clínicas y radiológicas, a partir de las cuales se propone un algoritmo de tratamiento urgente. Se excluyeron los casos con fracturas del cuello del astrágalo, cuerpo del calcáneo o fracturas-luxación de Chopart aisladas. Resultados: La mediana de edad fue de 48,5 años con predominio del sexo masculino (69,23%). Cinco pacientes sufrieron caídas-entorsis sobre el tobillo y los 8 restantes mecanismos de alta energía. Las luxaciones mediales (9) predominaron sobre las laterales (4). Además, 4 pacientes presentaron luxaciones abiertas, 2 de ellas tipo IIIC que precisaron amputación. Se solicitó TC en un 76,93% de pacientes y 10 presentaron lesiones óseas asociadas del pie. Se realizó cirugía mediante reducción abierta en todas las lesiones abiertas y en un caso en el que fracasó la reducción cerrada. Cinco pacientes precisaron fijador externo tipo delta. Se objetivó esclerosis subcondral articular en un 77,77% de los casos; si bien solo uno precisó artrodesis subtalar. Conclusiones: Las luxaciones periastragalinas son una urgencia traumatológica y precisan una reducción precoz e inmovilización posterior. La fijación externa temporal transarticular es una buena opción de inmovilización en luxaciones abiertas. Son lesiones graves con alta probabilidad de artrosis precoz.(AU)

Introduction and objectives: Subtalar dislocations are a rare entity (<1%) in traumatic foot injuries. There is a loss of anatomical relationship between the talus, calcaneus and scaphoid. There are only small-published series. Material and methods: We present a series of patients (N=13) with subtalar dislocations in which a descriptive analysis of the main epidemiological, clinical and radiological variables was carried out, from which an urgent treatment algorithm is proposed. Cases with fractures of the neck of the talus, body of the calcaneus, or isolated Chopart fracture-dislocations were excluded. Results: The median age was 48.5 years with a predominance of males (69.23%). Five patients suffered falls or sprained ankles and the other eight suffered high-energy mechanisms. The medial dislocations (nine) predominated over the lateral ones (four). In addition, four patients presented open dislocations, two of them type IIIC that required amputation. CT scans were requested in 76.93% of patients and 10 presented associated bone lesions of the foot. Open reduction surgery was performed in all open lesions and in one case in which closed reduction failed. Five patients required a delta-type external fixator. Subchondral articular sclerosis was observed in 77.77% of cases; although only one required subtalar arthrodesis. Conclusions: Subtalar dislocations are a traumatic emergency that require early reduction and subsequent immobilization. Transarticular temporary external fixation is a good immobilization option in open dislocations. They are serious lesions with a high probability of early osteoarthritis.(AU)

Subtalar dislocations: Analysis of a case series. Our urgent treatment algorithm. / Luxaciones periastragalinas: análisis de una serie de casos. Nuestro algoritmo de tratamiento urgente.

INTRODUCTION AND OBJECTIVES: Subtalar dislocations are a rare entity (<1%) in traumatic foot injuries. There is a loss of anatomical relationship between the talus, calcaneus and scaphoid. There are only small-published series. MATERIAL AND METHODS: We present a series of patients (N=13) with subtalar dislocations in which a descriptive analysis of the main epidemiological, clinical and radiological variables was carried out, from which an urgent treatment algorithm is proposed. Cases with fractures of the neck of the talus, body of the calcaneus, or isolated Chopart fracture-dislocations were excluded. RESULTS: The median age was 48.5 years with a predominance of males (69.23%). Five patients suffered falls or sprained ankles and the other eight suffered high-energy mechanisms. The medial dislocations (nine) predominated over the lateral ones (four). In addition, four patients presented open dislocations, two of them type IIIC that required amputation. CT scans were requested in 76.93% of patients and 10 presented associated bone lesions of the foot. Open reduction surgery was performed in all open lesions and in one case in which closed reduction failed. Five patients required a delta-type external fixator. Subchondral articular sclerosis was observed in 77.77% of cases; although only one required subtalar arthrodesis. CONCLUSIONS: Subtalar dislocations are a traumatic emergency that require early reduction and subsequent immobilization. Transarticular temporary external fixation is a good immobilization option in open dislocations. They are serious lesions with a high probability of early osteoarthritis.

[Translated article] Subtalar dislocations: Analysis of a case series. Our urgent treatment algorithm.

INTRODUCTION AND OBJECTIVES: Subtalar dislocations are a rare entity (<1%) in traumatic foot injuries. There is a loss of anatomical relationship between the talus, calcaneus and scaphoid. There are only small-published series. MATERIAL AND METHODS: We present a series of patients (N=13) with subtalar dislocations in which a descriptive analysis of the main epidemiological, clinical and radiological variables was carried out, from which an urgent treatment algorithm is proposed. Cases with fractures of the neck of the talus, body of the calcaneus, or isolated Chopart fracture-dislocations were excluded. RESULTS: The median age was 48.5 years with a predominance of males (69.23%). Five patients suffered falls or sprained ankles and the other eight suffered high-energy mechanisms. The medial dislocations (nine) predominated over the lateral ones (four). In addition, four patients presented open dislocations, two of them type IIIC that required amputation. CT scans were requested in 76.93% of patients and 10 presented associated bone lesions of the foot. Open reduction surgery was performed in all open lesions and in one case in which closed reduction failed. Five patients required a delta-type external fixator. Subchondral articular sclerosis was observed in 77.77% of cases; although only one required subtalar arthrodesis. CONCLUSIONS: Subtalar dislocations are a traumatic emergency that require early reduction and subsequent immobilisation. Transarticular temporary external fixation is a good immobilisation option in open dislocations. They are serious lesions with a high probability of early osteoarthritis.

Ipsilateral proximal and shaft femoral fractures: Results of two treatment strategies / Fracturas ipsilaterales proximales y diafisarias del fémur: resultados de 2 estrategias de tratamiento

Introduction: Ipsilateral proximal and shaft femoral fractures typically occur in young adults after high-energy trauma. No consensus exists regarding the optimal internal fixation device or surgical strategy for these complex fractures. Our main objective is to identify differences on outcomes and complications between patients treated with one or combined implants. Material and method: This is a single-center retrospective cohort study in patients with associated fractures of the proximal (31 AO) and shaft femur (32 AO). We divided the patients into two groups according to the use of single (Group I) or combined implants (Group II). Demographic, clinical, radiological, surgical data and development of complications were collected.Results: We identified 28 patients (19 men and 9 women) with an average age of 43 years. We used an anterograde femoral nail in group I (17 patients) and a retrograde femoral nail or a plate associated with hip lag screws or sliding hip screw in Group II (11 patients). Patients were followed up for 26.28 (9.12–62.88) months. Osteonecrosis of the femoral head, osteoarthritis, infection or nonunion was found in 9 patients (32%). No significant differences (p 0.70) were found in complications between two groups or between definitive surgical fixation before or after the first 24h. Conclusions: No differences in the development of complications or timing of definitive fixation were found between the use of one or combined implants in ipsilateral proximal femur and shaft fractures. Regardless of the implant chosen, an appropriate osteosynthesis technique is crucial, even so high complication rates are expected.

Introducción: Las fracturas ipsilaterales proximales y diafisarias del fémur suelen ocurrir en adultos jóvenes después de un traumatismo de alta energía. No existe consenso sobre el dispositivo de fijación interna óptimo o la estrategia quirúrgica para estas fracturas complejas. Nuestro principal objetivo es identificar las diferencias en los resultados y complicaciones entre los pacientes tratados con un implante o combinados. Material y método: Este es un estudio de cohorte retrospectivo unicéntrico en pacientes con fracturas asociadas del fémur proximal (31 AO) y diafisarias (32 AO). Dividimos a los pacientes en 2 grupos según el uso de implantes únicos (grupo i) o combinados (grupo ii). Se recogieron datos demográficos, clínicos, radiológicos, quirúrgicos y complicaciones. Resultados: Se identificaron 28 pacientes (19 hombres y 9 mujeres) con una edad promedio de 43 años. Utilizamos un clavo femoral anterógrado en el grupo i (17 pacientes) y un clavo femoral retrógrado o una placa con tornillos a compresión o tornillo deslizante de cadera en el grupo ii (11 pacientes). Los pacientes fueron seguidos durante 26,28 (9,12-62,88) meses. Se encontró osteonecrosis de la cabeza femoral, osteoartritis, infección o seudoartrosis en 9 pacientes (32%). No se encontraron diferencias significativas (p=0,70) en las complicaciones entre los 2 grupos o entre la fijación quirúrgica definitiva antes o después de las primeras 24h. Conclusiones: No se encontraron diferencias en el desarrollo de complicaciones o el momento de la fijación definitiva entre el uso de un implante o combinado en fracturas ipsilaterales de fémur proximal y diafisario. Independientemente del implante elegido, una técnica de osteosíntesis adecuada es crucial; aun así son esperables altas tasas de complicaciones.(AU)

[Artículo traducido] Fracturas ipsilaterales proximales y diafisarias del fémur: resultados de dos estrategias de tratamiento / Ipsilateral proximal and shaft femoral fractures: Results of two treatment strategies

Introduction: Ipsilateral proximal and shaft femoral fractures typically occur in young adults after high-energy trauma. No consensus exists regarding the optimal internal fixation device or surgical strategy for these complex fractures. Our main objective is to identify differences on outcomes and complications between patients treated with one or combined implants. Material and method: This is a single-center retrospective cohort study in patients with associated fractures of the proximal (31 AO) and shaft femur (32 AO). We divided the patients into two groups according to the use of single (Group I) or combined implants (Group II). Demographic, clinical, radiological, surgical data and development of complications were collected.Results: We identified 28 patients (19 men and 9 women) with an average age of 43 years. We used an anterograde femoral nail in group I (17 patients) and a retrograde femoral nail or a plate associated with hip lag screws or sliding hip screw in Group II (11 patients). Patients were followed up for 26.28 (9.12–62.88) months. Osteonecrosis of the femoral head, osteoarthritis, infection or nonunion was found in 9 patients (32%). No significant differences (p 0.70) were found in complications between two groups or between definitive surgical fixation before or after the first 24h. Conclusions: No differences in the development of complications or timing of definitive fixation were found between the use of one or combined implants in ipsilateral proximal femur and shaft fractures. Regardless of the implant chosen, an appropriate osteosynthesis technique is crucial, even so high complication rates are expected.

Introducción: Las fracturas ipsilaterales proximales y diafisarias del fémur suelen ocurrir en adultos jóvenes después de un traumatismo de alta energía. No existe consenso sobre el dispositivo de fijación interna óptimo o la estrategia quirúrgica para estas fracturas complejas. Nuestro principal objetivo es identificar las diferencias en los resultados y complicaciones entre los pacientes tratados con un implante o combinados. Material y método: Este es un estudio de cohorte retrospectivo unicéntrico en pacientes con fracturas asociadas del fémur proximal (31 AO) y diafisarias (32 AO). Dividimos a los pacientes en 2 grupos según el uso de implantes únicos (grupo i) o combinados (grupo ii). Se recogieron datos demográficos, clínicos, radiológicos, quirúrgicos y complicaciones. Resultados: Se identificaron 28 pacientes (19 hombres y 9 mujeres) con una edad promedio de 43 años. Utilizamos un clavo femoral anterógrado en el grupo i (17 pacientes) y un clavo femoral retrógrado o una placa con tornillos a compresión o tornillo deslizante de cadera en el grupo ii (11 pacientes). Los pacientes fueron seguidos durante 26,28 (9,12-62,88) meses. Se encontró osteonecrosis de la cabeza femoral, osteoartritis, infección o seudoartrosis en 9 pacientes (32%). No se encontraron diferencias significativas (p=0,70) en las complicaciones entre los 2 grupos o entre la fijación quirúrgica definitiva antes o después de las primeras 24h. Conclusiones: No se encontraron diferencias en el desarrollo de complicaciones o el momento de la fijación definitiva entre el uso de un implante o combinado en fracturas ipsilaterales de fémur proximal y diafisario. Independientemente del implante elegido, una técnica de osteosíntesis adecuada es crucial; aun así son esperables altas tasas de complicaciones.(AU)

Ipsilateral proximal and shaft femoral fractures: Results of two treatment strategies. / [Artículo traducido] Fracturas ipsilaterales proximales y diafisarias del fémur: resultados de dos estrategias de tratamiento.

INTRODUCTION: Ipsilateral proximal and shaft femoral fractures typically occur in young adults after high-energy trauma. No consensus exists regarding the optimal internal fixation device or surgical strategy for these complex fractures. Our main objective is to identify differences on outcomes and complications between patients treated with one or combined implants. MATERIAL AND METHOD: This is a single-center retrospective cohort study in patients with associated fractures of the proximal (31 AO) and shaft femur (32 AO). We divided the patients into two groups according to the use of single (GroupI) or combined implants (GroupII). Demographic, clinical, radiological, surgical data and development of complications were collected. RESULTS: We identified 28 patients (19 men and 9 women) with an average age of 43years. We used an anterograde femoral nail in GroupI (17 patients) and a retrograde femoral nail or a plate associated with hip lag screws or sliding hip screw in GroupII (11 patients). Patients were followed up for 26.28 (9.12-62.88) months. Osteonecrosis of the femoral head, osteoarthritis, infection or nonunion was found in 9 patients (32%). No significant differences (P=.70) were found in complications between two groups or between definitive surgical fixation before or after the first 24h. CONCLUSIONS: No differences in the development of complications or timing of definitive fixation were found between the use of one or combined implants in ipsilateral proximal femur and shaft fractures. Regardless of the implant chosen, an appropriate osteosynthesis technique is crucial, even so high complication rates are expected.

Ipsilateral proximal and shaft femoral fractures: Results of two treatment strategies.

INTRODUCTION: Ipsilateral proximal and shaft femoral fractures typically occur in young adults after high-energy trauma. No consensus exists regarding the optimal internal fixation device or surgical strategy for these complex fractures. Our main objective is to identify differences on outcomes and complications between patients treated with one or combined implants. MATERIAL AND METHOD: This is a single-center retrospective cohort study in patients with associated fractures of the proximal (31 AO) and shaft femur (32 AO). We divided the patients into two groups according to the use of single (Group I) or combined implants (Group II). Demographic, clinical, radiological, surgical data and development of complications were collected. RESULTS: We identified 28 patients (19 men and 9 women) with an average age of 43 years. We used an anterograde femoral nail in group I (17 patients) and a retrograde femoral nail or a plate associated with hip lag screws or sliding hip screw in Group II (11 patients). Patients were followed up for 26.28 (9.12-62.88) months. Osteonecrosis of the femoral head, osteoarthritis, infection or nonunion was found in 9 patients (32%). No significant differences (p 0.70) were found in complications between two groups or between definitive surgical fixation before or after the first 24h. CONCLUSIONS: No differences in the development of complications or timing of definitive fixation were found between the use of one or combined implants in ipsilateral proximal femur and shaft fractures. Regardless of the implant chosen, an appropriate osteosynthesis technique is crucial, even so high complication rates are expected. LEVEL OF EVIDENCE: IV. Grade of Recommendation: C.

On the evolution of the exclusion zone produced by hydrophilic surfaces: A contracted description.

After exciting scientific debates about its nature, the development of the exclusion zone, a region near hydrophilic surfaces from which charged colloidal particles are strongly expelled, has been finally traced back to the diffusiophoresis produced by unbalanced ion gradients. This was done by numerically solving the coupled Poisson equation for electrostatics, the two stationary Stokes equations for low Reynolds numbers in incompressible fluids, and the Nernst-Planck equation for mass transport. Recently, it has also been claimed that the leading mechanism behind the diffusiophoretic phenomenon is electrophoresis [Esplandiu et al., Soft Matter 16, 3717 (2020)]. In this paper, we analyze the evolution of the exclusion zone based on a one-component interaction model at the Langevin equation level, which leads to simple analytical expressions instead of the complex numerical scheme of previous works, yet being consistent with it. We manage to reproduce the evolution of the exclusion zone width and the mean-square displacements of colloidal particles we measure near Nafion, a perfluorinated polymer membrane material, along with all characteristic time regimes, in a unified way. Our findings are also strongly supported by complementary experiments using two parallel planar conductors kept at a fixed voltage, mimicking the hydrophilic surfaces, and some computer simulations.

Effects of the curvature gradient on the distribution and diffusion of colloids confined to surfaces.

The properties and behavior of colloids confined to move on curved surfaces offer a fertile ground for analysis since the geometric constraints induce specific features that are not available in flat spaces. Given their pertinence for biological and physicochemical processes, both with potential useful applications, the development of the concepts and methodology necessary for a deeper understanding of these unconventional systems is indeed an essential pursuit. The present study discusses a general and rigorous algorithm for the implementation of Brownian dynamics simulations that solves underlying difficulties and shortcomings inherent to conventional first-order schemes. Still based on the Ermak-McCammon recipe, our approach complements it with the higher-order geodesical projections of the elementary jumps generated on the associated tangent plane. This strategy, which warrants the locally isotropic propagation of non-interacting particles, is tested with a model system of colloidal particles interacting through a screened Coulomb potential while confined to move on ellipsoidal surfaces. This allows us to measure the effects prompted by the curvature gradient on the static and dynamic properties of this system. The varying curvature thus induces energetically favorable configurations in which the particles maximize their Euclidean distancing by crowding the regions with the largest Gaussian curvature, while withdrawing from those with the lowest. In turn, these inhomogeneous distributions provoke the anisotropic self-diffusion of the confined colloids, which is examined by exploiting the pertinent geodesic radial coordinates. The proficient methods under consideration thus allows dealing with the rich and remarkable new phenomena generated by any distinctive surface geometry.

Primary total hip arthroplasty in elderly patients over 85 years old: risks, complications and medium-long term results. / Artroplastia total primaria de cadera en pacientes mayores de 85 años: riesgos, complicaciones y resultados a medio-largo plazo.

INTRODUCTION: The elderly population candidate for total hip arthroplasty (THA) is increasing exponentially in developed countries, due to the high prevalence of osteoarthritis (OA). The objective is to identify the overall survival in patients over 85 years with primary OA who underwent THA. MATERIAL AND METHODS: Retrospective observational study in patients over 85 years with primary hip OA undergoing THA between 2012 and 2019. Demographic, clinical, comorbidity, complications, functionality and pain variables were collected. A descriptive analysis was performed, survival was estimated with the Kaplan-Meier method and the differences in pain and functionality before and after surgery with the McNemar-Bowker test. RESULTS: We included 66 patients, 40 women and 26 men with a mean age of 87.22 years, of whom 15 had high comorbidity (Charlson>2). Only 14 patients presented complications in the postoperative period, the most frequent was confusional syndrome (5); and the most serious was a death (1), with a median hospital stay of 8 days. Two cases of dislocation were detected over a mean follow-up of 3.61 years, without requiring revision surgery. Improvement of pain was evident after surgery (p<.0001). The median overall survival is 6.77 years, with no difference in survival adjusted by the Charlson index (p=.75) or by ASA anaesthetic group (p=.23). CONCLUSIONS: With good patient selection, THA is a good option for patients over 85 years of age with functional limitations or pain due to OA.

Assisted lipid deposition by reductive electrochemical aryldiazonium grafting and insertion of the antiport NhaA protein in this stable biomimetic membrane.

Quartz crystal microbalance studies have been carried out to monitor the fusion of lipid vesicles (pure 1,2-dimyristoyl-sn-glycero-3-phosphocholine, DMPC) and mixed vesicles (DMPC and 4-decylaniline). In order to increase the stability of the lipid deposits onto the electrodes, we have developed an original approach involving electrografting of adsorbed mixed vesicles. Aryldiazonium salts generated in situ from 4-decylaniline (4DA) present in adsorbed and fused mixed vesicles at the electrode surface allow their cathodic reduction and subsequent grafting. The stability of the supported lipid deposit has been shown to significantly increase from less than one day for pure DMPC to about two weeks with the lipid deposition assisted by electrochemical grafting. In this stable lipid deposit, the insertion of the sodium/proton antiporter membrane protein (NhaA) or its inactive mutant has been carried out by fusion of proteoliposomes. This has been followed by characterization of the inserted protein activity by cyclic voltammetry onto an electrode previously modified by an adsorbed pH sensor (2-anthraquinone sulfonate). Activation of the protein function by sodium ions leads to a shift of the interfacial pH and confirms the integrity of the immobilized NhaA.

Characterization of the elastic properties of extracellular matrix models by atomic force microscopy.

Tissue elasticity is a critical regulator of cell behavior in normal and diseased conditions like fibrosis and cancer. Since the extracellular matrix (ECM) is a major regulator of tissue elasticity and function, several ECM-based models have emerged in the last decades, including in vitro endogenous ECM, decellularized tissue ECM and ECM hydrogels. The development of such models has urged the need to quantify their elastic properties particularly at the nanometer scale, which is the relevant length scale for cell-ECM interactions. For this purpose, the versatility of atomic force microscopy (AFM) to quantify the nanomechanical properties of soft biomaterials like ECM models has emerged as a very suitable technique. In this chapter we provide a detailed protocol on how to assess the Young's elastic modulus of ECM models by AFM, discuss some of the critical issues, and provide troubleshooting guidelines as well as illustrative examples of AFM measurements, particularly in the context of cancer.

Racial and ethnic disparities in utilization of total knee arthroplasty among older women.

OBJECTIVE: To evaluate racial and ethnic disparities in utilization of total knee arthroplasty (TKA) in relation to demographic, health, and socioeconomic status variables. DESIGN: Prospective study of 102,767 Women's Health Initiative postmenopausal women initially aged 50-79, examining utilization rates of primary TKA between non-Hispanic Black/African American, non-Hispanic White, and Hispanic/Latina women (hereafter referred to as Black, White, and Hispanic). A total of 8,942 Black, 3,405 Hispanic, and 90,420 White women with linked Medicare claims data were followed until time of TKA, death, or transition from fee-for-service coverage. Absolute disparities were determined using utilization rates by racial/ethnic group and relative disparities quantified using multivariable hazards models in adjusting for age, arthritis, joint pain, mobility disability, body mass index, number of comorbidities, income, education, neighborhood socioeconomic status (SES), and geographic region. RESULTS: TKA utilization was higher among White women (10.7/1,000 person-years) compared to Black (8.5/1,000 person-years) and Hispanic women (7.6/1,000 person-years). Among women with health indicators for TKA including diagnosis of arthritis, moderate to severe joint pain, and mobility disability, Black and Hispanic women were significantly less likely to undergo TKA after adjusting for age [Black: HR (95% confidence interval) = 0.70 (0.63-0.79); Hispanic: HR = 0.58 (0.44-0.77)]. Adjustment for SES modestly attenuated the measured disparity, but significant differences remained [Black: HR = 0.75 (0.67-0.89); Hispanic: HR = 0.65 (0.47-0.89)]. CONCLUSIONS: Compared to White women, Black and Hispanic women were significantly less likely to undergo TKA after considering need and appropriateness for TKA and SES. Further investigation into personal-level and provider-level factors that may explain these disparities is warranted.

Evolutionary Spiking Neural Networks for Solving Supervised Classification Problems.

This paper presents a grammatical evolution (GE)-based methodology to automatically design third generation artificial neural networks (ANNs), also known as spiking neural networks (SNNs), for solving supervised classification problems. The proposal performs the SNN design by exploring the search space of three-layered feedforward topologies with configured synaptic connections (weights and delays) so that no explicit training is carried out. Besides, the designed SNNs have partial connections between input and hidden layers which may contribute to avoid redundancies and reduce the dimensionality of input feature vectors. The proposal was tested on several well-known benchmark datasets from the UCI repository and statistically compared against a similar design methodology for second generation ANNs and an adapted version of that methodology for SNNs; also, the results of the two methodologies and the proposed one were improved by changing the fitness function in the design process. The proposed methodology shows competitive and consistent results, and the statistical tests support the conclusion that the designs produced by the proposal perform better than those produced by other methodologies.

Contour changes after guided bone regeneration of large non-contained mandibular buccal bone defects using deproteinized bovine bone mineral and a porcine-derived collagen membrane: an experimental in vivo investigation.

OBJECTIVE: The objective of this study was to evaluate soft tissue contour changes after three different regenerative therapies in chronic ridge defects. MATERIAL AND METHODS: Buccal bone defects were created in the mandible of nine beagle dogs. Augmentation procedures were performed 3 months later using a bone replacement graft (BRG), resorbable collagen membrane (MBG), or a combination of both procedures (CBG). Silicone impressions were taken before tooth extraction (T1), before the augmentation procedure (T2), and 3 months after the regenerative surgeries (T3). Casts were optically scanned and stereolithography files were superimposed to analyze the horizontal changes in ridge contours. RESULTS: After defect creation, most part of the horizontal changes occurred 4 and 6 mm below the gingival margin. In the mesial defect (D1) at T3, the mean horizontal gain in MBG amounted to 0.47 ± 0.34 mm, 0.79 ± 0.67 mm in the BRG, and 0.87 ± 0.69 mm for the CBG. In the middle defect (D2), the mean changes for the MBG were 0.11 ± 0.31, 1.01 ± 0.91 for the BRG, and 0.98 ± 0.49 for the CBG. The mean changes in the distal defect (D3) amounted to 0.24 ± 0.72 for the MBG, 1.04 ± 0.92 for the BRG, and 0.86 ± 0.56 for the CBG. The differences reached significance in all defects for the comparison MBG-BRG and MBG-CBG, while similar parameters were observed for the comparison BRG-CBG. CONCLUSION: BRG and CBG were equally effective and superior to MBG in increasing the horizontal tissue contours. The augmentation seldom reached the values before extraction. CLINICAL RELEVANCE: Scaffolding materials are needed for contour augmentation when using resorbable collagen membranes.

Cellular and molecular characterization of gametogenic progression in ex vivo cultured prepuberal mouse testes.

BACKGROUND: Recently, an effective testis culture method using a gas-liquid interphase, capable of differentiate male germ cells from neonatal spermatogonia to spermatozoa has been developed. Nevertheless, this methodology needs deep analyses that allow future experimental approaches in basic, pathologic and/or reprotoxicologic studies. Because of this, we characterized at cellular and molecular levels the entire in vitro spermatogenic progression, in order to understand and evaluate the characteristics that define the spermatogenic process in ex vivo cultured testes compared to the in vivo development. METHODS: Testicular explants of CD1 mice aged 6 and 10 days post-partum were respectively cultured during 55 and 89 days. Cytological and molecular approaches were performed, analyzing germ cell proportion at different time culture points, meiotic markers immunodetecting synaptonemal complex protein SYCP3 by immunocytochemistry and the relative expression of different marker genes along the differentiation process by Reverse Transcription - quantitative Polymerase Chain Reaction. In addition, microRNA and piwi-interactingRNA profiles were also evaluated by Next Generation Sequencing and bioinformatic approaches. RESULTS: The method promoted and maintained the spermatogenic process during 89 days. At a cytological level we detected spermatogenic development delays of cultured explants compared to the natural in vivo process. The expression of different spermatogenic stages gene markers correlated with the proportion of different cell types detected in the cytological preparations. CONCLUSIONS: In vitro progression analysis of the different spermatogenic cell types, from both 6.5 dpp and 10.5 dpp testes explants, has revealed a relative delay in relation to in vivo process. The expression of the genes studied as biomarkers correlates with the cytologically and functional detected progression and differential expression identified in vivo. After a first analysis of deep sequencing data it has been observed that as long as cultures progress, the proportion of microRNAs declined respect to piwi-interactingRNAs levels that increased, showing a similar propensity than which happens in in vivo spermatogenesis. Our study allows to improve and potentially to control the ex vivo spermatogenesis development, opening new perspectives in the reproductive biology fields including male fertility.

Nintedanib selectively inhibits the activation and tumour-promoting effects of fibroblasts from lung adenocarcinoma patients.

BACKGROUND: Nintedanib is a clinically approved multikinase receptor inhibitor to treat non-small cell lung cancer with adenocarcinoma (ADC) histology in combination with docetaxel, based on the clinical benefits reported on ADC but not on squamous cell carcinoma (SCC), which are the two most common histologic lung cancer subtypes. METHODS: We examined the potential role of tumour-associated fibroblasts (TAFs) in the differential effects of nintedanib in ADC and SCC. Because TAFs are largely quiescent and activated in histologic sections, we focused on the antifibrotic effects of nintedanib on TAFs stimulated with the potent fibroblast activator TGF-ß1, which is upregulated in lung cancer. RESULTS: Nintedanib dose-dependently inhibited the TGF-ß1-induced expression of a panel of pro-fibrotic activation markers in both ADC-TAFs and control fibroblasts derived from uninvolved lung parenchyma, whereas such inhibition was very modest in SCC-TAFs. Remarkably, nintedanib abrogated the stimulation of growth and invasion in a panel of carcinoma cell lines induced by secreted factors from activated TAFs in ADC but not SCC, thereby supporting that TGF-ß signalling and aberrant TAF-carcinoma cross-talk is regulated by different mechanisms in ADC and SCC. CONCLUSIONS: These results reveal that nintedanib is an effective inhibitor of fibrosis and its associated tumour-promoting effects in ADC, and that the poor antifibrotic response of SCC-TAFs to nintedanib may contribute to the differential clinical benefit observed in both subtypes. Our findings also support that preclinical models based on carcinoma-TAF interactions may help defining the mechanisms of the poor antifibrotic response of SCC-TAFs to nintedanib and testing new combined therapies to further expand the therapeutic effects of this drug in solid tumours.