The Neurolipid Atlas: a lipidomics resource for neurodegenerative diseases uncovers cholesterol as a regulator of astrocyte reactivity impaired by ApoE4.

Lipid changes in the brain have been implicated in many neurodegenerative diseases including Alzheimer's Disease (AD), Parkinson's disease and Amyotrophic Lateral Sclerosis. To facilitate comparative lipidomic research across brain-diseases we established a data commons named the Neurolipid Atlas, that we have pre-populated with novel human, mouse and isogenic induced pluripotent stem cell (iPSC)-derived lipidomics data for different brain diseases. We show that iPSC-derived neurons, microglia and astrocytes display distinct lipid profiles that recapitulate in vivo lipotypes. Leveraging multiple datasets, we show that the AD risk gene ApoE4 drives cholesterol ester (CE) accumulation in human astrocytes recapitulating CE accumulation measured in the human AD brain. Multi-omic interrogation of iPSC-derived astrocytes revealed that cholesterol plays a major role in astrocyte interferon-dependent pathways such as the immunoproteasome and major histocompatibility complex (MHC) class I antigen presentation. We show that through enhanced cholesterol esterification ApoE4 suppresses immune activation of astrocytes. Our novel data commons, available at neurolipidatlas.com, provides a user-friendly tool and knowledge base for a better understanding of lipid dyshomeostasis in neurodegenerative diseases.

Genomic analysis of inbreeding level, kinship and breed relationships in Creole cattle from South America.

The conservation of animal genetic resources refers to measures taken to prevent the loss of genetic diversity in livestock populations, including the protection of breeds from extinction. Creole cattle populations have suffered a drastic reduction in recent decades owing to absorbent crosses or replacement with commercial breeds of European or Indian origin. Genetic characterization can serve as a source of information for conservation strategies to maintain genetic variation. The objective of this work was to evaluate the levels of inbreeding and kinship through the use of genomic information. A total of 903 DNAs from 13 cattle populations from Argentina, Bolivia and Uruguay were genotyped using an SNP panel of 48 K. Also, a dataset of 76 K SNPs from Peruvian Creole was included. Two inbreeding indices (FROH and Fhat2) and kinship relationships were calculated. In addition, effective population size (Ne), linkage disequilibrium, population composition and phylogenetic relationships were estimated. In Creole cattle, FROH ranged from 0.14 to 0.03, and Fhat2 was close to zero. The inferred Ne trends exhibited a decline toward the present for all populations, whereas Creole cattle presented a lower magnitude of Ne than foreign breeds. Cluster analysis clearly differentiated the taurine and Zebu components (K2) and showed that Bolivian Creole cattle presented Zebu gene introgression. Despite the population reduction, Creole populations did not present extreme values of consanguinity and kinship and maintain high levels of genetic diversity. The information obtained in this work may be useful for planning conservation programmes for these valuable local animal genetic resources.

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)

Tandem Mass Spectrometry across Platforms.

PubChem serves as a comprehensive repository, housing over 100 million unique chemical structures representing the breadth of our chemical knowledge across numerous fields including metabolism, pharmaceuticals, toxicology, cosmetics, agriculture, and many more. Rapid identification of these small molecules increasingly relies on electrospray ionization (ESI) paired with tandem mass spectrometry (MS/MS), particularly by comparison to genuine standard MS/MS data sets. Despite its widespread application, achieving consistency in MS/MS data across various analytical platforms remains an unaddressed concern. This study evaluated MS/MS data derived from one hundred molecular standards utilizing instruments from five manufacturers, inclusive of quadrupole time-of-flight (QTOF) and quadrupole orbitrap "exactive" (QE) mass spectrometers by Agilent (QTOF), Bruker (QTOF), SCIEX (QTOF), Waters (QTOF), and Thermo QE. We assessed fragment ion variations at multiple collisional energies (0, 10, 20, and 40 eV) using the cosine scoring algorithm for comparisons and the number of fragments observed. A parallel visual analysis of the MS/MS spectra across instruments was conducted, consistent with a standard procedure that is used to circumvent the still prevalent issue of mischaracterizations as shown for dimethyl sphingosine and C20 sphingosine. Our analysis revealed a notable consistency in MS/MS data and identifications, with fragment ions' m/z values exhibiting the highest concordance between instrument platforms at 20 eV, the other collisional energies (0, 10, and 40 eV) were significantly lower. While moving toward a standardized ESI MS/MS protocol is required for dependable molecular characterization, our results also underscore the continued importance of corroborating MS/MS data against standards to ensure accurate identifications. Our findings suggest that ESI MS/MS manufacturers, akin to the established norms for gas chromatography mass spectrometry instruments, should standardize the collision energy at 20 eV across different instrument platforms.

[Translated article] Better results in consolidation of hallux metatarsophalangeal arthrodesis with dorsal plate and interfragmentary compression screw.

BACKGROUND AND AIMS: The first metatarsophalangeal joint arthrodesis is indicated for the treatment of various pathologies as a technique to reduce pain and improve the support of the first radius. Numerous surgical techniques and fixation methods have been described, with the combination of a dorsal plate and an interfragmentary screw being the one that has shown to be the most stable construct in biomechanical studies. Our aim is to analyze the radiological results after metatarsophalangeal arthrodesis of the hallux using a dorsal plate associated or not with an interfragmentary screw. The differences in terms of consolidation rates and complications in patients diagnosed with hallux rigidus, hallux valgus, hallux varus and failure of previous surgeries were evaluated. MATERIALS AND METHODS: A retrospective cohort study of 55 patients with a mean age of 65.10 years in whom a dorsal plate was used was performed. Patients were divided into two groups depending on whether or not an interfragmentary screw was used. The minimum follow-up was 6 months after surgery. The assessment of the pre and postoperative radiological results was based on the variation of the hallux angle, the intermetatarsal angle and the dorsal metatarsophalangeal angle of the hallux, as well as the cases of nonunion identified in each study group. RESULTS: The radiological results, statistically significant differences (p<0.05) were only found in the dorsal metatarsophalangeal angle between both study groups. No statistically significant differences were found regarding the radiological evaluation of the pre and postoperative hallux angle and intermetatarsal angle. An equal decrease of each angles was observed in both study groups. Regarding the consolidation rate, statistically significant differences (p<0.05) were found between group A, which associated an interfragmentary screw, presenting a consolidation rate of 92%, and group B, which did not associate an interfragmentary screw, and that presented a union rate of 63%. CONCLUSION: Hallux metatarsophalangeal arthrodesis of the hallux with a dorsal plate and interfragmentary screw show best results regarding consolidation rate and complications compared to those cases in which an interfragmentary screw was not used.

Spatially and temporally resolved metabolome of the human oral cavity.

Saliva is a complex bodily fluid composed of secretions by major and minor salivary glands. Salivary glands and their secretions are known to be unevenly distributed in the human oral cavity. Moreover, saliva flow rate and composition vary across locations and time of the day. This remarkable heterogeneity of salivary secretions suggests that different subtypes of saliva fulfill different functions. By coupling a non-invasive and facile collection method with comprehensive metabolomic profiling, we investigated the spatial and temporal distributions of salivary components. We identified location-specific metabolite profiles, novel oscillating metabolites, and location-specific diurnal patterns. In summary, our study paves the way for a deeper and more comprehensive understanding of the complex dynamics and functionalities of the salivary metabolome and its integration in multi-omics studies related to oral and systemic (patho-)physiology.

Invited review: Ketone biology-The shifting paradigm of ketones and ketosis in the dairy cow.

Ketosis is currently regarded as a major metabolic disorder of dairy cows, reflective of the animal's efforts to adapt to energy deficit while transitioning into lactation. Currently viewed as a pathology by some, ketosis is associatively implicated in milk production losses and peripartal health complications that increase the risk of early removal of cows from the herd, thus carrying economic losses for dairy farmers and jeopardizing the sustainability of the dairy industry. Despite decades of intense research in the mitigation of ketosis and its sequelae, our ability to lessen its purported effects remains limited. Moreover, the association of ketosis to reduced milk production and peripartal disease is often erratic and likely mired by concurrent potential confounders. In this review, we discuss the potential reasons for these apparent paradoxes in the light of currently available evidence, with a focus on the limitations of observational research and the necessary steps to unambiguously identify the effects of ketosis on cow health and performance via controlled randomized experimentation. A nuanced perspective is proposed that considers the dissociation of ketosis-as a disease-from healthy hyperketonemia. Furthermore, in consideration of a growing body of evidence that highlights positive roles of ketones in the mitigation of metabolic dysfunction and chronic diseases, we consider the hypothetical functions of ketones as health-promoting metabolites and ponder on their potential usefulness to enhance dairy cow health and productivity.

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.

Preclinical Evaluation of the ATR Inhibitor BAY 1895344 as a Radiosensitizer for Head and Neck Squamous Cell Carcinoma.

PURPOSE: Despite aggressive multimodal treatment that typically includes definitive or adjuvant radiation therapy (RT), locoregional recurrence rates approach 50% for patients with locally advanced human papillomavirus (HPV)-negative head and neck squamous cell carcinoma (HNSCC). Thus, more effective therapeutics are needed to improve patient outcomes. We evaluated the radiosensitizing effects of ataxia telangiectasia and RAD3-related (ATR) inhibitor (ATRi) BAY 1895344 in preclinical models of HNSCC. METHODS AND MATERIALS: Murine and human HPV-negative HNSCC cells (MOC2, MOC1, JHU-012) were treated with vehicle or ATRi with or without 4 Gy. Checkpoint kinase 1 phosphorylation and DNA damage (γH2AX) were evaluated by Western blot, and ATRi half-maximal inhibitory concentration was determined by MTT assay for HNSCC cells and immortalized murine oral keratinocytes. In vitro radiosensitization was tested by clonogenic assay. Cell cycle distribution and mitotic catastrophe were evaluated by flow cytometry. Mitotic aberrations were quantified by fluorescent microscopy. Tumor growth delay and survival were assessed in mice bearing MOC2 or JHU-012 transplant tumors treated with vehicle, ATRi, RT (10 Gy × 1 or 8 Gy × 3), or combined ATRi + RT. RESULTS: ATRi caused dose-dependent reduction in checkpoint kinase 1 phosphorylation at 1 hour post-RT (4 Gy) and dose-dependent increase in γH2AX at 18 hours post-RT. Addition of RT to ATRi led to decreased BAY 1895344 half-maximal inhibitory concentration in HNSCC cell lines but not in normal tissue surrogate immortalized murine oral keratinocytes. Clonogenic assays demonstrated radiosensitization in the HNSCC cell lines. ATRi abrogated the RT-induced G2/M checkpoint, leading to mitosis with unrepaired DNA damage and increased mitotic aberrations (multinucleated cells, micronuclei, nuclear buds, nucleoplasmic bridges). ATRi and RT significantly delayed tumor growth in MOC2 and JHU-012 in vivo models, with improved overall survival in the MOC2 model. CONCLUSIONS: These findings demonstrated that BAY 1895344 increased in vitro and in vivo radiosensitivity in HPV-negative HNSCC preclinical models, suggesting therapeutic potential warranting evaluation in clinical trials for patients with locally advanced or recurrent HPV-negative HNSCC.

Better results in consolidation of hallux metatarsophalangeal arthrodesis with dorsal plate and interfragmentary compression screw. / Mejores resultados en la consolidación de la artrodesis metatarsofalángica del hallux con placa dorsal y tornillo de compresión interfragmentario.

INTRODUCTION AND AIMS: The first metatarsophalangeal joint arthrodesis is indicated for the treatment of various pathologies as a technique to reduce pain and improve the support of the first radius. Numerous surgical techniques and fixation methods have been described, with the combination of a dorsal plate and an interfragmentary screw being the one that has shown to be the most stable construct in biomechanical studies. Our aim is to analyze the radiological results after metatarsophalangeal arthrodesis of the hallux using a dorsal plate associated or not with an interfragmentary screw. The differences in terms of consolidation rates and complications in patients diagnosed with hallux rigidus, hallux valgus, hallux varus and failure of previous surgeries were evaluated. MATERIAL AND METHODS: A retrospective cohort study of 55 patients with a mean age of 65.10 years in whom a dorsal plate was used was performed. Patients were divided into 2 groups depending on whether or not an interfragmentary screw was used. The minimum follow-up was 6 months after surgery. The assessment of the pre and postoperative radiological results was based on the variation of the hallux angle, the intermetatarsal angle and the dorsal metatarsophalangeal angle of the hallux, as well as the cases of nonunion identified in each study group. RESULTS: The radiological results, statistically significant differences (p<0.05) were only found in the dorsal metatarsophalangeal angle between both study groups. No statistically significant differences were found regarding the radiological evaluation of the pre and postoperative hallux angle and intermetatarsal angle. An equal decrease of each angles was observed in both study groups. Regarding the consolidation rate, statistically significant differences (p<0.05) were found between group A, which associated an interfragmentary screw, presenting a consolidation rate of 92%, and group B, which did not associate an interfragmentary screw, and that presented a union rate of 63%. CONCLUSIONS: Hallux metatarsophalangeal arthrodesis of the hallux with a dorsal plate and interfragmentary screw show best results regarding consolidation rate and complications compared to those cases in which an interfragmentary screw was not used.

Predictors of Prediabetes Among Communities Without a Family History of Type 2 Diabetes Mellitus: A Case-Control Study.

Background Prediabetes is the golden period to promote, prevent, or delay diabetes mellitus (DM) conversion. This study aims to assess the risk predictors associated with prediabetes among communities without a family history of type 2 DM (T2DM). Methodology This case-control study involved 570 participants (265 prediabetes cases and the same number of age-matched controls) in Palembang, Indonesia. Each participant is willing to take fasting blood glucose, lipid profile tests, and physical examinations. Results Multivariate analysis of this study revealed that significant risk predictors identified were occupation in the informal sector (aOR = 3.28; 95% CI = 1.64-6.58; p-value = 0.001), diastolic blood pressure of 80-89 mmHg (aOR = 2.18; 95% CI = 1.35-3.52; p-value = 0.001), diastolic blood pressure of 90-99 mmHg (aOR = 2.09; 95% CI= 1.15-3.82; p-value = 0.016), with an aOR = 5.80 (95% CI= 3.71-9.05; p-value <0.001). triglyceride-glucose index was the dominant risk predictor for prediabetes. Conclusions Knowing who is most vulnerable can guide the efficient allocation of promotion and prevention resources. This finding proves essential consideration for health promoters emphasizing a healthy diet and lifestyle by maintaining diastolic pressure and triglyceride glucose (TyG) index while considering the occupation in populations without a family history of T2DM.

Optimal transport of active particles induced by substrate concentration oscillations.

We show the existence of a stochastic resonant regime in the transport of active colloidal particles under confinement. The periodic addition of substrate to the system causes the spectral amplification to exhibit a maximum for an optimal noise level value. The consequence of this is that particles can travel longer distances with lower fuel consumption. The stochastic resonance phenomenon found allows the identification of optimal scenarios for the transport of active particles, enabling them to reach regions that are otherwise difficult to access, and may therefore find applications in transport in cell membranes and tissues for medical treatments and soil remediation.

A Clinically Selected Staphylococcus aureus clpP Mutant Survives Daptomycin Treatment by Reducing Binding of the Antibiotic and Adapting a Rod-Shaped Morphology.

Daptomycin is a last-resort antibiotic used for the treatment of infections caused by Gram-positive antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). Treatment failure is commonly linked to accumulation of point mutations; however, the contribution of single mutations to resistance and the mechanisms underlying resistance remain incompletely understood. Here, we show that a single nucleotide polymorphism (SNP) selected during daptomycin therapy inactivates the highly conserved ClpP protease and is causing reduced susceptibility of MRSA to daptomycin, vancomycin, and ß-lactam antibiotics as well as decreased expression of virulence factors. Super-resolution microscopy demonstrated that inactivation of ClpP reduced binding of daptomycin to the septal site and diminished membrane damage. In both the parental strain and the clpP strain, daptomycin inhibited the inward progression of septum synthesis, eventually leading to lysis and death of the parental strain while surviving clpP cells were able to continue synthesis of the peripheral cell wall in the presence of 10× MIC daptomycin, resulting in a rod-shaped morphology. To our knowledge, this is the first demonstration that synthesis of the outer cell wall continues in the presence of daptomycin. Collectively, our data provide novel insight into the mechanisms behind bacterial killing and resistance to this important antibiotic. Also, the study emphasizes that treatment with last-line antibiotics is selective for mutations that, like the SNP in clpP, favor antibiotic resistance over virulence gene expression.

High-Throughput Venomics.

In this study, we present high-throughput (HT) venomics, a novel analytical strategy capable of performing a full proteomic analysis of a snake venom within 3 days. This methodology comprises a combination of RP-HPLC-nanofractionation analytics, mass spectrometry analysis, automated in-solution tryptic digestion, and high-throughput proteomics. In-house written scripts were developed to process all the obtained proteomics data by first compiling all Mascot search results for a single venom into a single Excel sheet. Then, a second script plots each of the identified toxins in so-called Protein Score Chromatograms (PSCs). For this, for each toxin, identified protein scores are plotted on the y-axis versus retention times of adjacent series of wells in which a toxin was fractionated on the x-axis. These PSCs allow correlation with parallel acquired intact toxin MS data. This same script integrates the PSC peaks from these chromatograms for semiquantitation purposes. This new HT venomics strategy was performed on venoms from diverse medically important biting species; Calloselasma rhodostoma, Echis ocellatus, Naja pallida, Bothrops asper, Bungarus multicinctus, Crotalus atrox, Daboia russelii, Naja naja, Naja nigricollis, Naja mossambica, and Ophiophagus hannah. Our data suggest that high-throughput venomics represents a valuable new analytical tool for increasing the throughput by which we can define venom variation and should greatly aid in the future development of new snakebite treatments by defining toxin composition.

Fracturas de maléolo posterior: indicaciones de fijación y vías de abordaje / Posterior malleolar fractures: Indications and surgical approaches

Las fracturas del maléolo posterior están presentes en 7-44% del total de fracturas de tobillo.El objetivo de esta revisión es conocer la evidencia actual sobre las indicaciones de fijación interna y la elección del abordaje quirúrgico para el tratamiento de estas fracturas.Las indicaciones clásicas de fijación eran el tamaño mayor a 25-30% de la superficie articular y el desplazamiento mayor a 2 mm; sin embargo, la evidencia actual sugiere que, en lugar del tamaño, se deben considerar factores tales como la inestabilidad sindesmal, el escalón articular mayor a 1-2 mm, la impactación de la superficie articular y la presencia de fragmentos intercalares.Al comparar las vías de abordaje, la bibliografía apoya el uso de los abordajes posteriores, reservando la recomendación de abordaje anterior para casos excepcionales.Para el tratamiento de esta lesión es fundamental conocer la anatomía del tobillo y considerar los factores descritos, además de la presencia de lesiones concomitantes.(AU)

Posterior malleolus fractures are frequent injuries, present in 7–44% of all ankle fractures.The objective of this study is to review the evidence to indicate the fixation of this fracture and to choose the appropriate surgical approach.The classic indications for fixation were fragment size greater than 25–30% of the articular surface and displacement greater than 2 mm. However, current evidence suggests that, rather than size, factors such as syndesmotic instability, intra-articular step-off greater than 1–2 mm, plafond impaction and the presence of intercalary fragments should be considered.When comparing the different surgical approaches, the literature supports the use of posterior approaches and reserves the recommendation of the traditional approach for exceptional cases.For the treatment of this injury it is essential to know the anatomy of the ankle and to consider all the factors described above, in addition to the presence of concomitant injuries.(AU)

[Translated article] Posterior malleolar fractures: Indications and surgical approaches / Fracturas de maléolo posterior: indicaciones de fijación y vías de abordaje

Las fracturas del maléolo posterior están presentes en 7-44% del total de fracturas de tobillo.El objetivo de esta revisión es conocer la evidencia actual sobre las indicaciones de fijación interna y la elección del abordaje quirúrgico para el tratamiento de estas fracturas.Las indicaciones clásicas de fijación eran el tamaño mayor a 25-30% de la superficie articular y el desplazamiento mayor a 2 mm; sin embargo, la evidencia actual sugiere que, en lugar del tamaño, se deben considerar factores tales como la inestabilidad sindesmal, el escalón articular mayor a 1-2 mm, la impactación de la superficie articular y la presencia de fragmentos intercalares.Al comparar las vías de abordaje, la bibliografía apoya el uso de los abordajes posteriores, reservando la recomendación de abordaje anterior para casos excepcionales.Para el tratamiento de esta lesión es fundamental conocer la anatomía del tobillo y considerar los factores descritos, además de la presencia de lesiones concomitantes.(AU)

Posterior malleolus fractures are frequent injuries, present in 7–44% of all ankle fractures.The objective of this study is to review the evidence to indicate the fixation of this fracture and to choose the appropriate surgical approach.The classic indications for fixation were fragment size greater than 25–30% of the articular surface and displacement greater than 2 mm. However, current evidence suggests that, rather than size, factors such as syndesmotic instability, intra-articular step-off greater than 1–2 mm, plafond impaction and the presence of intercalary fragments should be considered.When comparing the different surgical approaches, the literature supports the use of posterior approaches and reserves the recommendation of the traditional approach for exceptional cases.For the treatment of this injury it is essential to know the anatomy of the ankle and to consider all the factors described above, in addition to the presence of concomitant injuries.(AU)

Membrane lipid remodeling modulates γ-secretase processivity.

Imbalances in the amounts of amyloid-ß peptides (Aß) generated by the membrane proteases ß- and γ-secretase are considered as a trigger of Alzheimer's disease (AD). Cell-free studies of γ-secretase have shown that increasing membrane thickness modulates Aß generation but it has remained unclear if these effects are translatable to cells. Here we show that the very long-chain fatty acid erucic acid (EA) triggers acyl chain remodeling in AD cell models, resulting in substantial lipidome alterations which included increased esterification of EA in membrane lipids. Membrane remodeling enhanced γ-secretase processivity, resulting in the increased production of the potentially beneficial Aß37 and/or Aß38 species in multiple cell lines. Unexpectedly, we found that the membrane remodeling stimulated total Aß secretion by cells expressing WT γ-secretase but lowered it for cells expressing an aggressive familial AD mutant γ-secretase. We conclude that EA-mediated modulation of membrane composition is accompanied by complex lipid homeostatic changes that can impact amyloidogenic processing in different ways and elicit distinct γ-secretase responses, providing critical implications for lipid-based AD treatment strategies.