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1.
Proc Natl Acad Sci U S A ; 121(14): e2316101121, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38547068

RESUMEN

Though YB6 and LaB6 share the same crystal structure, atomic valence electron configuration, and phonon modes, they exhibit drastically different phonon-mediated superconductivity. YB6 superconducts below 8.4 K, giving it the second-highest critical temperature of known borides, second only to MgB2. LaB6 does not superconduct until near-absolute zero temperatures (below 0.45 K), however. Though previous studies have quantified the canonical superconductivity descriptors of YB6's greater Fermi-level (Ef) density of states and higher electron-phonon coupling (EPC), the root of this difference has not been assessed with full detail of the electronic structure. Through chemical bonding, we determine low-lying, unoccupied 4f atomic orbitals in lanthanum to be the key difference between these superconductors. These orbitals, which are not accessible in YB6, hybridize with π B-B bonds and bring this π-system lower in energy than the σ B-B bonds otherwise at Ef. This inversion of bands is crucial: the optical phonon modes we show responsible for superconductivity cause the σ-orbitals of YB6 to change drastically in overlap, but couple weakly to the π-orbitals of LaB6. These phonons in YB6 even access a crossing of electronic states, indicating strong EPC. No such crossing in LaB6 is observed. Finally, a supercell (the M k-point) is shown to undergo Peierls-like effects in YB6, introducing additional EPC from both softened acoustic phonons and the same electron-coupled optical modes as in the unit cell. Overall, we find that LaB6 and YB6 have fundamentally different mechanisms of superconductivity, despite their otherwise near-identity.

2.
Mol Biol Evol ; 41(2)2024 Feb 01.
Artículo en Inglés | MEDLINE | ID: mdl-38285634

RESUMEN

Rainforest hunter-gatherers from Southeast Asia are characterized by specific morphological features including a particularly dark skin color (D), short stature (S), woolly hair (W), and the presence of steatopygia (S)-fat accumulation localized in the hips (DSWS phenotype). Based on previous evidence in the Andamanese population, we first characterized signatures of adaptive natural selection around the calcium-sensing receptor gene in Southeast Asian rainforest groups presenting the DSWS phenotype and identified the R990G substitution (rs1042636) as a putative adaptive variant for experimental follow-up. Although the calcium-sensing receptor has a critical role in calcium homeostasis by directly regulating the parathyroid hormone secretion, it is expressed in different tissues and has been described to be involved in many biological functions. Previous works have also characterized the R990G substitution as an activating polymorphism of the calcium-sensing receptor associated with hypocalcemia. Therefore, we generated a knock-in mouse for this substitution and investigated organismal phenotypes that could have become adaptive in rainforest hunter-gatherers from Southeast Asia. Interestingly, we found that mouse homozygous for the derived allele show not only lower serum calcium concentration but also greater body weight and fat accumulation, probably because of enhanced preadipocyte differentiation and lipolysis impairment resulting from the calcium-sensing receptor activation mediated by R990G. We speculate that such differential features in humans could have facilitated the survival of hunter-gatherer groups during periods of nutritional stress in the challenging conditions of the Southeast Asian tropical rainforests.


Asunto(s)
Polimorfismo Genético , Receptores Sensibles al Calcio , Animales , Humanos , Ratones , Calcio , Fenotipo , Receptores Sensibles al Calcio/genética , Selección Genética
3.
J Proteome Res ; 23(2): 560-573, 2024 02 02.
Artículo en Inglés | MEDLINE | ID: mdl-38252700

RESUMEN

One of the primary goals of systems medicine is the detection of putative proteins and pathways involved in disease progression and pathological phenotypes. Vascular cognitive impairment (VCI) is a heterogeneous condition manifesting as cognitive impairment resulting from vascular factors. The precise mechanisms underlying this relationship remain unclear, which poses challenges for experimental research. Here, we applied computational approaches like systems biology to unveil and select relevant proteins and pathways related to VCI by studying the crosstalk between cardiovascular and cognitive diseases. In addition, we specifically included signals related to oxidative stress, a common etiologic factor tightly linked to aging, a major determinant of VCI. Our results show that pathways associated with oxidative stress are quite relevant, as most of the prioritized vascular cognitive genes and proteins were enriched in these pathways. Our analysis provided a short list of proteins that could be contributing to VCI: DOLK, TSC1, ATP1A1, MAPK14, YWHAZ, CREB3, HSPB1, PRDX6, and LMNA. Moreover, our experimental results suggest a high implication of glycative stress, generating oxidative processes and post-translational protein modifications through advanced glycation end-products (AGEs). We propose that these products interact with their specific receptors (RAGE) and Notch signaling to contribute to the etiology of VCI.


Asunto(s)
Trastornos del Conocimiento , Disfunción Cognitiva , Demencia Vascular , Humanos , Trastornos del Conocimiento/complicaciones , Trastornos del Conocimiento/diagnóstico , Disfunción Cognitiva/genética , Estrés Oxidativo , Cognición , Demencia Vascular/genética , Demencia Vascular/diagnóstico
4.
J Cogn Neurosci ; 36(3): 460-474, 2024 03 01.
Artículo en Inglés | MEDLINE | ID: mdl-38165746

RESUMEN

Although it is well established that self-related information can rapidly capture our attention and bias cognitive functioning, whether this self-bias can affect language processing remains largely unknown. In addition, there is an ongoing debate as to the functional independence of language processes, notably regarding the syntactic domain. Hence, this study investigated the influence of self-related content on syntactic speech processing. Participants listened to sentences that could contain morphosyntactic anomalies while the masked face identity (self, friend, or unknown faces) was presented for 16 msec preceding the critical word. The language-related ERP components (left anterior negativity [LAN] and P600) appeared for all identity conditions. However, the largest LAN effect followed by a reduced P600 effect was observed for self-faces, whereas a larger LAN with no reduction of the P600 was found for friend faces compared with unknown faces. These data suggest that both early and late syntactic processes can be modulated by self-related content. In addition, alpha power was more suppressed over the left inferior frontal gyrus only when self-faces appeared before the critical word. This may reflect higher semantic demands concomitant to early syntactic operations (around 150-550 msec). Our data also provide further evidence of self-specific response, as reflected by the N250 component. Collectively, our results suggest that identity-related information is rapidly decoded from facial stimuli and may impact core linguistic processes, supporting an interactive view of syntactic processing. This study provides evidence that the self-reference effect can be extended to syntactic processing.


Asunto(s)
Potenciales Evocados , Percepción del Habla , Humanos , Potenciales Evocados/fisiología , Lenguaje , Semántica , Lingüística , Electroencefalografía , Percepción del Habla/fisiología
5.
Genet Med ; 26(1): 100991, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37791544

RESUMEN

PURPOSE: We conducted qualitative interviews with patients with cancer and providers to identify gaps in clinical care and highlight care delivery solutions for the return of secondary germline findings. METHODS: Twelve patients and 19 cancer providers from the United States were interviewed between January 2019 and May 2021. Interviews elicited feedback about patient information needs, emotional responses to secondary findings, and recommendations for improving pre-test education. RESULTS: Patients' responses ranged from gratitude to regret, depending on how much pre-test counseling they received before tumor testing. Providers cited insufficient clinic time as a major barrier to pretest education, favoring online support tools and standardized pre-test education models. Providers had differing perspectives on how pre-test education should be integrated into clinical workflows but agreed that it should include the differences between somatic and germline testing, the likelihood of medically actionable findings, and the possibility of being referred to a genetics provider. CONCLUSION: The spectrum of participants' responses to their secondary findings underscores the importance of adequate pre-test discussions before somatic sequencing. Although educational interventions could address patients' information needs and augment traditional pre-test counseling, health care systems, labs, and genetic providers may be called on to play greater roles in pre-test education.


Asunto(s)
Neoplasias , Humanos , Estados Unidos , Neoplasias/genética , Neoplasias/terapia , Atención a la Salud
6.
J Arthroplasty ; 39(2): 374-378, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-37598778

RESUMEN

BACKGROUND: To assess any clinically important difference in functional outcome over 10 years after primary total knee arthroplasty (TKA). METHODS: A prospective registry-based observational cohort study including 309 patients older than 60 years who underwent primary TKA. Patients were assessed at 1, 3, 5, 7 and 10 postoperative years with the Knee Society scores (KSS) and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Clinically important improvement was defined according to the minimal clinically important difference (MCID). Patients were also categorized as type A (unilateral knee osteoarthritis), type B (bilateral knee osteoarthritis) or type C (various sites of osteoarthritis). RESULTS: The mean age at the TKA surgery was 69.2 (SD 7.3) years, 197 (63.7%) were women.Maximum postoperative improvements in functional scores occurred at 3 postoperative years, remained relatively stable up to 5-year. There were significant decreases in all KSS and WOMAC scores at 7-year follow-up (P = .001), remained stable up to 10-year. At 10-year, functional scores were significantly higher than preoperatively (P = .001). Differences between maximum scores at 3-year and those at 10-year were significantly lesser than MCID in all scores (P = .001). In multivariate analysis, type-C patient at TKA surgery was the only significant predictor of unsuccessful KSS score and dissatisfaction at 10-year follow-up. CONCLUSION: Primary TKA provides clinically important improvements in functional and quality of life outcomes over 10-year follow-up compared to preoperatively. Although there were statistically significant declines in KSS and WOMAC scores from 3 to 10 years, the differences were lesser than the MCID.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Femenino , Anciano , Masculino , Osteoartritis de la Rodilla/cirugía , Calidad de Vida , Estudios Longitudinales , Resultado del Tratamiento , Articulación de la Rodilla/cirugía
7.
J Clin Ultrasound ; 2024 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-38867304

RESUMEN

PURPOSE: The gastrocnemius venous system presents different anatomical variants. There have been described four locations of myofascial trigger points (MTrPs) in this muscle. However, no studies have analyzed the coincidence between vessels and MTrPs present in the gastrocnemius. Therefore, the main objective was to study the anatomical variability of the venous system by ultrasound and its coincidence with the location of the MTrPs. METHODS: A total of 100 lower limbs were studied. The gastrocnemius vessels were analyzed one by one by sector (medial, central, and lateral), quantifying the number of vessels, their distribution, and the coincidence with MTrPs. RESULTS: All muscle heads showed at least one vessel per section. A large variability was observed, from one to eight vessels per muscle head, with the most frequent number being three in the gastrocnemius medialis and two in the gastrocnemius lateralis. In all cases, the location of the vessels coincided with the MTrPs. CONCLUSIONS: The proximal gastrocnemius venous pattern is very variable between subjects in number of vessels and distribution, which has made it impossible to define a "safe" approach window for invasive procedures without ultrasound guidance. The coincidence between the clinical location of MTrPs of the gastrocnemius and the presence of vessels is total.

8.
Alzheimers Dement ; 20(1): 538-548, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37727082

RESUMEN

INTRODUCTION: This study examined the relationship between blood-brain-barrier permeability (BBBp), measured by cerebrospinal fluid/serum albumin ratio (QAlb), and cognitive decline progression in a clinical cohort. METHODS: This prospective observational study included 334 participants from the BIODEGMAR cohort. Cognitive decline progression was defined as an increase in Global Deterioration Scale and/or Clinical Dementia Rating scores. Associations between BBBp, demographics, and clinical factors were explored. RESULTS: Male sex, diabetes mellitus, and cerebrovascular burden were associated with increased log-QAlb. Vascular cognitive impairment patients had the highest log-QAlb levels. Among the 273 participants with valid follow-up data, 154 (56.4%) showed cognitive decline progression. An 8% increase in the hazard of clinical worsening was observed for each 10% increase in log-QAlb. DISCUSSION: These results suggest that increased BBBp in individuals with cognitive decline may contribute to clinical worsening, pointing to potential targeted therapies. QAlb could be a useful biomarker for identifying patients with a worse prognosis.


Asunto(s)
Barrera Hematoencefálica , Disfunción Cognitiva , Humanos , Masculino , Estudios Longitudinales , Encéfalo , Permeabilidad
9.
Rev Esp Enferm Dig ; 2024 Apr 30.
Artículo en Inglés | MEDLINE | ID: mdl-38685904

RESUMEN

The complication rate for Pancreaticoduodenectomy (PD) is 40-50% in most published series and mortality can raise up to 4-5% even in high-volume centers. Severe portal hypertension secondary to liver disease is associated to high perioperative mortality and therefore is considered a contraindication for PD. No standardized management exists for surgically resectable patients with periampullary cancer and severe portal hypertension. The aim of this case study is to analyse the treatment alternatives in patients with periampullary cancer and severe portal hypertension and focus into the surgical treatment of these patients. We present the case of a 67 year-old patient case with a resectable ampullary cancer and portal hypertension managed with Preoperative Transjugular Intrahepatic Portosystemic Shunt (TIPS) to allow a PD. We present a literature review on the use of preoperative TIPS in patients who are candidates to PD. Neoadjuvant TIPS can be safely used in selected patients with severe portal hypertension who need a PD.

10.
Plant Physiol ; 190(4): 2137-2154, 2022 11 28.
Artículo en Inglés | MEDLINE | ID: mdl-36111879

RESUMEN

In Arabidopsis (Arabidopsis thaliana), the plastidial isoform of phosphoglucose isomerase (PGI1) mediates photosynthesis, metabolism, and development, probably due to its involvement in the synthesis of isoprenoid-derived signals in vascular tissues. Microbial volatile compounds (VCs) with molecular masses of <45 Da promote photosynthesis, growth, and starch overaccumulation in leaves through PGI1-independent mechanisms. Exposure to these compounds in leaves enhances the levels of GLUCOSE-6-PHOSPHATE/PHOSPHATE TRANSLOCATOR2 (GPT2) transcripts. We hypothesized that the PGI1-independent response to microbial volatile emissions involves GPT2 action. To test this hypothesis, we characterized the responses of wild-type (WT), GPT2-null gpt2-1, PGI1-null pgi1-2, and pgi1-2gpt2-1 plants to small fungal VCs. In addition, we characterized the responses of pgi1-2gpt2-1 plants expressing GPT2 under the control of a vascular tissue- and root tip-specific promoter to small fungal VCs. Fungal VCs promoted increases in growth, starch content, and photosynthesis in WT and gpt2-1 plants. These changes were substantially weaker in VC-exposed pgi1-2gpt2-1 plants but reverted to WT levels with vascular and root tip-specific GPT2 expression. Proteomic analyses did not detect enhanced levels of GPT2 protein in VC-exposed leaves and showed that knocking out GPT2 reduced the expression of photosynthesis-related proteins in pgi1-2 plants. Histochemical analyses of GUS activity in plants expressing GPT2-GUS under the control of the GPT2 promoter showed that GPT2 is mainly expressed in root tips and vascular tissues around hydathodes. Overall, the data indicated that the PGI1-independent response to microbial VCs involves resetting of the photosynthesis-related proteome in leaves through long-distance GPT2 action.


Asunto(s)
Proteínas de Arabidopsis , Arabidopsis , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Glucosa-6-Fosfato/metabolismo , Proteómica , Arabidopsis/metabolismo , Glucosa-6-Fosfato Isomerasa/metabolismo , Almidón/metabolismo , Glucosa/metabolismo , Fosfatos/metabolismo
11.
Inorg Chem ; 62(23): 9044-9053, 2023 Jun 12.
Artículo en Inglés | MEDLINE | ID: mdl-37227233

RESUMEN

We report herein a series of neutral trans-thiocyanate mononuclear spin crossover (SCO) complexes, [FeIIL(NCS)2] (1-4), based on tetradentate ligands L obtained by reaction of N-substituted 1,2,3-triazolecarbaldehyde with 1,3-propanediamine or 2,2-dimethyl-1,3-diaminopropane [L = N1,N3-bis((1,5-dimethyl-1H-1,2,3-triazol-4-yl)methylene)propane-1,3-diamine/-2,2-dimethylpropane-1,3-diamine, 1/2 and N1,N3-bis((1-ethyl/1-propyl-1H-1,2,3-triazol-4-yl)methylene)-2,2-dimethylpropane-1,3-diamine, 3/4]. The thermal-induced SCO behavior is characterized by abrupt transitions with an average critical temperature (ΔT1/2)/hysteresis loop width (ΔThyst) in the range 190-252/5-14 K, while the photo-generated metastable high-spin (HS) phases are characterized by TLIESST temperatures in the range 44-59 K. Single crystal analysis shows that except 1, all compounds experience reversible symmetry breaking coupled with the thermal SCO. Furthermore, 4 experiences an additional phase transition at ca. 290 K responsible for the coexistence of two HS phases quenched at 10 K through LIESST and TIESST effects. The molecules form hexagonally packed arrays sustained by numerous weak CH···S and C···C/S···C/N···C bonds involving polar coordination cores, while non-polar pendant aliphatic substituents are segregated inside, occupying hexagonal channels. Energy framework analysis of complexes with one step SCO transition (1, 2, and 4) shows a correlation between the cooperativity and the amplitude of changes in the molecule-molecule interactions in the lattice at the SCO transition.

12.
Arch Womens Ment Health ; 26(5): 639-650, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37540344

RESUMEN

The co-occurrence of substance use disorders (SUD) and other mental disorders (OMD) is assumed to be high, but the details are uncertain in Spain. The objective of the present study was to know the prevalence of this comorbidity, as well as the pharmacological treatment, both in specific addiction treatment networks and in mental health networks, with a gender perspective. Observational, multicenter study, with a randomized sample, of patients under treatment for SUD or OMD in Spain (N = 1783). A specific questionnaire, collecting sociodemographic and clinical variables, diagnosed SUD and OMD, and prescribed psychotropic drugs, was completed by treating clinicians. Differences between females and males were searched. A high prevalence of OMD was found in those patients treated for their SUD (71%), and also of diagnoses of SUD (59%) in people treated for OMD. Significant relationships between addiction to certain substances and specific mental disorders were found (with no main differences between women and men). The treatments for OMD were very common in the addiction treatment networks, but that of SUDs in those patients treated in the mental health networks was less than expected. A high prescription of benzodiazepines was found. Women were less frequently diagnosed with cannabis, opioid, and especially cocaine use disorders, and they had fewer psychotic disorders and more affective, anxiety, sleep, and eating disorders, with the rest being the same, including personality disorders. Women had fewer treatments with agonists and more with antagonists, and more prescriptions of anxiolytics and antidepressants. This study provides preliminary information on the coexistence in routine clinical practice of addictive disorders and other mental disorders in Spain, and on the treatment provided, and shows differences in prevalence and clinical characteristics, and especially in treatment approaches between women and men. Thus, should be useful to adapt the treatment response with greater precision, and with a gender perspective.


Asunto(s)
Trastornos Mentales , Trastornos Psicóticos , Trastornos Relacionados con Sustancias , Masculino , Humanos , Femenino , Trastornos Mentales/psicología , Trastornos Relacionados con Sustancias/epidemiología , Trastornos Relacionados con Sustancias/psicología , Comorbilidad , Trastornos de la Personalidad/epidemiología , Trastornos Psicóticos/epidemiología
13.
Knee Surg Sports Traumatol Arthrosc ; 31(3): 1011-1017, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36114843

RESUMEN

PURPOSE: The purpose of this study was to investigate the changes in engagement in physical, leisure and social activities in older adults following primary TKA. METHODS: A prospective study of 106 patients with a mean age of 72.6 (SD 7.4) years undergoing primary TKA was performed. Physical, social and leisure activities performed by the patients preoperatively and postoperatively at 3-year were recorded. Activities were selected according to the age, and grouped as passive, moderate and high intensity. The energy spent in each activity was expressed in Metabolic Equivalent of Task (MET) units. Charlson Comorbidity Index, Mini-mental test and Western Ontario and McMaster Universities (WOMAC) scores were also used. Multivariate analysis was used to identify predictors of active patients. RESULTS: Mean WOMAC significantly improved from preoperative (34.8, SD 11.8) to final follow-up (74.4, SD 11.1) (p = 0.001), and the mean energy spent increased from 10.7 (SD 13.6) to 28.2 (SD 16.2) MET-hour weekly (p = 0.001) with a decrease in the passive activities and increase in the moderate activities. However, the participation in high-intensity activities according to age was negligible. Only 65 (61.3%) patients were considered active postoperatively (weekly spending ≥ 40 MET), although the WOMAC scores were not significantly different between active and sedentary patients. Active patients compared with sedentary patients had a significant increase in engagement in physical, social and leisure activities, and a decrease in passive activities. Female gender (p = 0.037), less preoperatively participation in passive activities (p = 0.042), and greater participation in social activities (p = 0.027) were significant predictors of active patients at the final follow-up. CONCLUSION: Overall, most patients increased their activity level postoperatively. However, 38.6% of patients had no increased engagement in moderate physical, social or leisure activities at the medium-term despite improvements in pain and function provided by TKA. LEVEL OF EVIDENCE: II.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Osteoartritis de la Rodilla , Humanos , Femenino , Anciano , Estudios Prospectivos , Resultado del Tratamiento , Dolor/cirugía , Actividades Recreativas , Osteoartritis de la Rodilla/cirugía
14.
Rev Panam Salud Publica ; 47: e62, 2023.
Artículo en Español | MEDLINE | ID: mdl-37066127

RESUMEN

The objective of this article is to describe the experience in Chile, during 2021 and 2022, with the validation of COVID-19 vaccines administered abroad and the main obstacles during the implementation of this process. This validation is given throughout South America and, in the case of Chile, it has been a successful undertaking with the validation of more than two million vaccines from different countries. Validation is a systematic process involving reviews conducted by trained professionals, which helps maintain international relations with other countries and fulfill the objectives set forth by the health authority. Despite the project's success, it has brought to light situations such as digital gaps in the population and differences in the reporting systems and types of vaccines administered in each country. The following solutions have been proposed: a public contact center for users having difficulty with the technology; more flexible requirements for validation; and the possibility of continuing with the vaccination program in Chile, always focused on protecting the population, reducing the potential risk of disease transmission, and maintaining public health.


O objetivo deste artigo é descrever a experiência com o processo de registro de vacinação contra a COVID-19 no Chile em 2021 e 2022 e identificar os principais obstáculos encontrados na implementação. Na América do Sul, as vacinações são registradas e, no caso do Chile, esse foi um processo bem-sucedido, com a validação de mais de 2 milhões de vacinações feitas em outros países. Trata-se de um processo sistemático de revisão e aprovação realizado por profissionais capacitados, que permitiu manter as relações internacionais com outros países e cumprir os objetivos propostos pela autoridade sanitária. Apesar de seu sucesso, o projeto trouxe à tona vários entraves, como lacunas digitais na população, diferenças nos sistemas de registro de vacinação e discrepâncias nos tipos de vacinas administradas em cada país. Foram propostas soluções, como a criação de um centro de atendimento para usuários com dificuldades em lidar com a tecnologia, o relaxamento das exigências para obter o registro da vacinação e a possibilidade de continuar com o esquema de vacinação no Chile, sempre com o objetivo de proteger a população e, assim, reduzir o risco de transmissão da doença e preservar a saúde pública.

15.
Int J Mol Sci ; 24(2)2023 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-36674792

RESUMEN

Alzheimer's disease (AD) is known to be caused by amyloid ß-peptide (Aß) misfolded into ß-sheets, but this knowledge has not yet led to treatments to prevent AD. To identify novel molecular players in Aß toxicity, we carried out a genome-wide screen in Saccharomyces cerevisiae, using a library of 5154 gene knock-out strains expressing Aß1-42. We identified 81 mammalian orthologue genes that enhance Aß1-42 toxicity, while 157 were protective. Next, we performed interactome and text-mining studies to increase the number of genes and to identify the main cellular functions affected by Aß oligomers (oAß). We found that the most affected cellular functions were calcium regulation, protein translation and mitochondrial activity. We focused on SURF4, a protein that regulates the store-operated calcium channel (SOCE). An in vitro analysis using human neuroblastoma cells showed that SURF4 silencing induced higher intracellular calcium levels, while its overexpression decreased calcium entry. Furthermore, SURF4 silencing produced a significant reduction in cell death when cells were challenged with oAß1-42, whereas SURF4 overexpression induced Aß1-42 cytotoxicity. In summary, we identified new enhancer and protective activities for Aß toxicity and showed that SURF4 contributes to oAß1-42 neurotoxicity by decreasing SOCE activity.


Asunto(s)
Enfermedad de Alzheimer , Péptidos beta-Amiloides , Animales , Humanos , Péptidos beta-Amiloides/genética , Péptidos beta-Amiloides/toxicidad , Péptidos beta-Amiloides/química , Calcio/metabolismo , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/metabolismo , Muerte Celular , Canales de Calcio/genética , Fragmentos de Péptidos/genética , Fragmentos de Péptidos/toxicidad , Fragmentos de Péptidos/metabolismo , Mamíferos/metabolismo , Proteínas de la Membrana/genética , Proteínas de la Membrana/metabolismo
16.
Arch Orthop Trauma Surg ; 143(7): 4173-4179, 2023 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-36456765

RESUMEN

OBJECTIVE: There are scarce data on the mortality after hip fracture surgery for patients treated in the most recent years. The objective of this study was to analyze whether the overall initiatives introduced over the last decade for elderly patients with hip fractures had a positive impact on the 1-year mortality. METHODS: Patients treated during 2010-2012 were compared with patients treated during 2018-2020 for all-cause 1-year mortality. Variables influencing mortality were collected based on the literature, including demographic, comorbidity, cognitive status, and preinjury physical function. Crude mortalities were compared between periods, as well as with the expected mortality in the general population adjusted for age, gender, and year of surgery using the standardized mortality ratio (SMR). A multivariate model was used to identify mortality risk factors. RESULTS: 591 patients older than 65 years were treated during 2010-2012 and 642 patients during 2018-2020. The mean age increased significantly between periods (78.9 vs. 82.6 years, respectively, p = 0.001) in both genders, together with an increase in comorbidity (p = 0.014). The in-hospital mortality risk had no significant difference between periods (2.5 vs. 2.0%, p = 0.339), but the 30-day mortality risk (8.3 vs. 5.5%, p = 0.031) and 1-year mortality risk (16.1 vs. 11.9%, p = 0.023) declined significantly. However, 1-year mortality in 2020 had an excess of 1.33 in SMR. Age older than 80 years, male gender, and Charlson comorbidity index > 2 were significant predictors of 1-year mortality. CONCLUSION: The important evolution achieved in the last decade for the management of patients with hip fracture surgery has led to a significant decline in 1-year mortality, but the 1-year mortality remains significantly higher compared to the general population of similar age and gender.


Asunto(s)
Fracturas de Cadera , Humanos , Masculino , Femenino , Anciano , Anciano de 80 o más Años , Comorbilidad , Factores de Riesgo , Estudios Retrospectivos
17.
Arch Orthop Trauma Surg ; 143(6): 3431-3437, 2023 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-36243782

RESUMEN

OBJECTIVE: To investigate whether the functional outcomes were affected by the change in posterior tibial slope (PTS) after using a predetermined PTS for primary cruciate-retaining total knee arthroplasty (CR-TKA). METHODS: Prospective cohort study of 152 patients who underwent primary CR-TKA with a standardized PTS of 5º regardless of the native PTS. Patients were classified postoperatively in two ways. Firstly, according to the PTS change from preoperative to postoperative (increased or decreased PTS group). Secondly, according to the PTS difference between preoperative and postoperative ≤ 4º (group A) and > 4º (group B). The functional outcomes were assessed with the Knee Society Scores (KSS), McMaster Universities Osteoarthritis Index questionnaire (WOMAC), and range of motion (ROM). Preoperative and postoperative PTS were measured on lateral knee radiographs. RESULTS: The minimum follow-up was 5 year. There were no significant differences at the final follow-up in functional outcomes between increased (88 patients) and decreased (64 patients) PTS groups. Likewise, there were no significant differences in functional outcomes between group A (79 patients) and group B (73 patients). In multivariate analysis, the PTS change was not significant predictor for improvement in functional outcome (OR 1.08; 95% CI 0.70-1.40; p = 0.061). CONCLUSION: The PTS change between preoperative and postoperative has no influence on the functional outcomes using a CR-TKA. A standardized PTS regardless of the native is a reliable procedure for primary CR-TKA.


Asunto(s)
Artroplastia de Reemplazo de Rodilla , Prótesis de la Rodilla , Osteoartritis de la Rodilla , Ligamento Cruzado Posterior , Humanos , Artroplastia de Reemplazo de Rodilla/métodos , Articulación de la Rodilla/diagnóstico por imagen , Articulación de la Rodilla/cirugía , Ligamento Cruzado Posterior/cirugía , Estudios Prospectivos , Osteoartritis de la Rodilla/cirugía , Rango del Movimiento Articular
18.
Rev Esp Enferm Dig ; 2023 Jul 14.
Artículo en Inglés | MEDLINE | ID: mdl-37449514

RESUMEN

Hepatotoxicity is defined as a liver injury induced by a drug or a non-pharmacological agent like herbal medications or dietary supplements. Red yeast rice is rich in monacolin K, which has the same chemical structure as lovastatin, reason why it has been used for the management of hiperlipidemia. A 62 years old woman presented to the emergency service with 38.5ºC fever, coluric orine and loss of weight in the previous 3 weeks. The patient was taking RYR since the week before to the initial symptoms. Mixed hepatocellular and cholestatic acute hepatitis was diagnosed. Autoimmune liver serology resulted positive. Total DILI RECAM Score was 8 (highly probable DILI). Conservative treatment with exclusion of RYR was decided and during follow-up bilirubin and transaminases gradually dropped off. It has been reported a few cases of hepatitis associated to the use of RYR, promoted by a toxic or immunogenic metabolite. Cross-reactions may justify positive autoantibodies so hepatotoxicity should not be discard as a diagnose.

19.
Rev Med Chil ; 151(2): 170-176, 2023 Feb.
Artículo en Español | MEDLINE | ID: mdl-38293852

RESUMEN

BACKGROUND: The success of breast cancer (BC) treatment depends largely on the clinical-histological characteristics of the patient. Immunohistochemical (IHC) Breast Cancer Subtypes are crucial for therapeutic purposes. AIM: To determine the relevance and prevalence of the histopathological parameters and molecular subtypes of BC among women attending public health services. MATERIAL AND METHODS: A retrospective cross-sectional study was carried out in 199 female patients with histopathological diagnosis of breast cancer, treated at a Guayaquil city hospital in Ecuador, from January 2014 to December 2017. RESULTS: Luminal A carcinoma was the most prevalent tumor in the studied women (54%). Thirty seven percent of patients did not have nodal involvement, 40% had one to three lymph nodes involved and 2% had 10 or more nodes involved. Most patients had a tumor size > 2 and ≤ 5 cm (72%) and moderately differentiated specifications (57%). CONCLUSIONS: The study allowed the characterization of breast cancer according to the prevalence of molecular subtypes and clinical and histological characteristics. These factors determine therapeutic behaviors that optimize the use of the limited resources of the Public Health System.


Asunto(s)
Neoplasias de la Mama , Carcinoma , Humanos , Femenino , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Estudios Retrospectivos , Estudios Transversales , Ecuador/epidemiología , Pronóstico , Receptor ErbB-2
20.
J Am Chem Soc ; 144(31): 14297-14309, 2022 08 10.
Artículo en Inglés | MEDLINE | ID: mdl-35900921

RESUMEN

Little is known about the mechanisms behind the bistability (memory) of molecular spin transition compounds over broad temperature ranges (>100 K). To address this point, we report on a new discrete FeII neutral complex [FeIIL2]0 (1) based on a novel asymmetric tridentate ligand 2-(5-(3-methoxy-4H-1,2,4-triazol-3-yl)-6-(1H-pyrazol-1-yl))pyridine (L). Due to the asymmetric cone-shaped form, in the lattice, the formed complex molecules stack into a one-dimensional (1D) supramolecular chain. In the case of the rectangular supramolecular arrangement of chains in methanolates 1-A and 1-B (both orthorhombic, Pbcn) differing, respectively, by bent and extended spatial conformations of the 3-methoxy groups (3MeO), a moderate cooperativity is observed. In contrast, the hexagonal-like arrangement of supramolecular chains in polymorph 1-C (monoclinic, P21/c) results in steric coupling of the transforming complex species with the peripheral flipping 3MeO group. The group acts as a supramolecular latch, locking the huge geometric distortion of complex 1 and in turn the trigonal distortion of the central FeII ion in the high-spin state, thereby keeping it from the transition to the low-spin state over a large thermal range. Analysis of the crystal packing of 1-C reveals significantly changing patterns of close intermolecular interactions on going between the phases substantiated by the energy framework analysis. The detected supramolecular mechanism leads to a record-setting robust 105 K wide hysteresis spanning the room temperature region and an atypically large TLIESST relaxation value of 104 K of the photoexcited high-spin state. This work highlights a viable pathway toward a new generation of cleverly designed molecular memory materials.


Asunto(s)
Compuestos Ferrosos , Compuestos Ferrosos/química , Ligandos , Conformación Molecular , Temperatura
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