Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 619
Filter
1.
Percept Mot Skills ; : 315125241278532, 2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39259972

ABSTRACT

Perceptual-cognitive skills are crucial in successfully managing information and decision-making in sports, particularly in high-pressure environments. We examined 16 basketball referees' on-the-court visual search behavior by comparing referees of different experience levels (experienced, n = 8; and novice, n = 8) and different court positions. Participants' visual search behavior was analyzed during 20 live gameplay situations using eye-tracking technology. Dependent variables were the number of eye fixations, mean fixation time, and total fixation time on selected areas of interest; and independent variables were the referees' experience and visual angles (lead and trail referee positions). Experienced referees exhibited significantly lower total fixation time than novice referees (p = .009). Referees in the trail position showed more fixations of shorter duration and a greater focus on the basket than those in the lead position. Our findings suggest that the visual search behavior of basketball referees varies with their court position and experience. These data provide valuable insights into referees' complex visual search patterns in the real-game context, and they highlight the importance of considering viewing angle and experience in future research.

2.
Article in English | MEDLINE | ID: mdl-39291952

ABSTRACT

BACKGROUND: Lymphedema of the upper limbs and persistent pain are frequent sequelae after surgical treatment of breast cancer. AIM: The aim of this paper was to analyze the upper limb volume, pressure pain threshold, neural range of motion, pain intensity, kinesiophobia, pain hypervigilance and catastrophizing in patients with and without lymphoedema after breast cancer surgery. Secondly, we aimed to investigated the association between upper limb volume and these variables. DESIGN: Descriptive observational study. SETTING: Faculty of Health Sciences of the University of Granada. POPULATION: Fifty-eight post-surgical breast cancer survivors, 29 with upper limb lymphoedema and 29 without lymphoedema. METHODS: We measured upper limb volume (perimetric method). Also, pressure pain thresholds were assessed with a digital algometer, neural range of motion (neurodynamic test for radial, ulnar and median nerves), pain intensity (visual analogue scale), kinesiophobia, pain hypervigilance and catastrophizing (validated tests). To detect differences between the groups for the measurement variables we performed a t-test for independent samples analysis. A simple linear regression analysis adjusting for age and body mass index was performed to check the association among upper limb volume and pain variables in the group with lymphoedema. RESULTS: The analysis showed that lymphoedema group had lower pressure pain threshold bilaterally in the masseter (origin P≤0.036; insertion P≤0.046), temporalis (insertion P≤0.021), suboccipitalis (P≤0.036); second (P≤0.014), third (P≤0.001) and tenth rib (P≤0.001); affected side of the temporalis (origin P=0.025); temporomandibular joint (P=0.024); neural range of motion in the median nerve (P=0.047), ulnar (P=0.042) on the affected side and radial (P=0.039) on the unaffected side; and greater kinesiophobia (P=0.042). Linear regression analysis only showed a significant association between upper limb volume and neural range of motion in the radial nerve (P=0.020) in the lymphedema group. No significant associations were obtained for the rest of variables. CONCLUSIONS: These findings suggest that the presence of lymphoedema may contribute to an increased level of generalized mechanosensitivity and fear to movement in this population. CLINICAL REHABILITATION IMPACT: Upper limb lymphedema can lead to heightened mechanosensitivity and movement-related fear in breast cancer survivors. Therefore, fast track rehabilitation approach should be focus in screening and rehabilitation methods for detection and control this sequalae.

3.
Hum Vaccin Immunother ; 20(1): 2385175, 2024 Dec 31.
Article in English | MEDLINE | ID: mdl-39161115

ABSTRACT

Broad benefits of vaccination programs are well acknowledged but difficult to measure, especially when considering all vaccines included in a National Immunization Program (NIP). The aim was to conduct a cost-benefit analysis of the entire NIP in Spain, and an expanded NIP including four potential additional programs. A cost-benefit analysis was performed in Excel to assess the economic and health benefits (€) of vaccinating a single cohort of newborns over a lifetime horizon compared to no vaccination, from a societal perspective: firstly, according to the 2020 NIP in Spain (including 2021 recommendation for herpes zoster in 65-year-olds); and secondly, with an expanded NIP (adding rotavirus and meningococcal B in infants, and pertussis booster in adults aged >65 years and herpes zoster in all adults >50 years). The main inputs were taken from published literature and Spanish databases. Results were presented as a benefit-cost ratio (economic benefit per €1 invested). A cohort of 343,126 newborns were included in the analysis. The total investment needed to vaccinate the cohort throughout their lifetime, according to the 2020 NIP and the expanded NIP, was estimated at €168.5 million and €275.5 million, respectively. Potential economic benefits were €772.2 million and €803.0 million, respectively. The societal benefit-cost ratio was €4.58 and €2.91 per €1 invested, respectively. Even with the addition of new vaccination programs, the Spanish NIP yielded positive benefit-cost ratios from the societal perspective, demonstrating that NIPs spanning the full life course are an efficient public health measure.


Subject(s)
Cost-Benefit Analysis , Immunization Programs , Vaccination , Humans , Spain , Immunization Programs/economics , Infant, Newborn , Vaccination/economics , Aged , Infant , Middle Aged , Adult , Male , Female
4.
Science ; 385(6710): 738-743, 2024 Aug 16.
Article in English | MEDLINE | ID: mdl-39146421

ABSTRACT

Memory consolidation involves the synchronous reactivation of hippocampal cells active during recent experience in sleep sharp-wave ripples (SWRs). How this increase in firing rates and synchrony after learning is counterbalanced to preserve network stability is not understood. We discovered a network event generated by an intrahippocampal circuit formed by a subset of CA2 pyramidal cells to cholecystokinin-expressing (CCK+) basket cells, which fire a barrage of action potentials ("BARR") during non-rapid eye movement sleep. CA1 neurons and assemblies that increased their activity during learning were reactivated during SWRs but inhibited during BARRs. The initial increase in reactivation during SWRs returned to baseline through sleep. This trend was abolished by silencing CCK+ basket cells during BARRs, resulting in higher synchrony of CA1 assemblies and impaired memory consolidation.


Subject(s)
Action Potentials , CA1 Region, Hippocampal , Cholecystokinin , Memory Consolidation , Pyramidal Cells , Sleep , Animals , Male , Mice , CA1 Region, Hippocampal/physiology , CA2 Region, Hippocampal/physiology , Cholecystokinin/metabolism , Interneurons/physiology , Learning/physiology , Memory Consolidation/physiology , Pyramidal Cells/physiology , Sleep/physiology
5.
Eur J Surg Oncol ; 50(11): 108642, 2024 Aug 24.
Article in English | MEDLINE | ID: mdl-39213699

ABSTRACT

BACKGROUND: Locally advanced colon cancer is a high-risk condition for tumour recurrence with poor survival. The current treatment is surgery followed by adjuvant chemotherapy based on fluoropyrimidines and oxaliplatin. This approach has improved the oncological outcomes on this population, however the mucinous condition has not been studied in depth and although the evidence is weak, it is thought to have a worse response to systemic chemotherapy. The CHEMUCCA study aims to answer this question. OBJECTIVE: To evaluate the effectiveness of adjuvant systemic chemotherapy using the disease-free survival for stage II and III mucinous colon cancer who underwent surgical resection plus systemic adjuvant chemotherapy vs. surgery alone. PATIENTS AND METHODS: Retrospective analytical study including patients diagnosed with high-risk stage II and stage III colon cancer, treated between 2010 and 2021, with a minimum follow-up of 3 years. Demographic variables and tumour features were analysed. The primary endpoint was disease-free survival. Log rank test and Cox regression were used. RESULTS: Of 1134 patients with high-risk stage II and III colon cancer disease, 206 (18,17 %) had mucinous histology and 928 (81,83 %) had non-mucinous histology. 708 patients who received adjuvant chemotherapy, 129 (62,62 %) in mucinous group and 579 (62,39 %) in the non-mucinous group. Adjuvant systemic chemotherapy in stage II and III mucinous colon cancer improved the DFS (HR = 0.58 [95 % CI 0.37-0.91]; p = 0,017). However, in a stratified analysis, patients with high-risk stage II mucinous colon cancer showed no benefit with this approach (HR = 0.4541 [95 % CI 0.19-1.03]; p = 0.06). CONCLUSION: Adjuvant chemotherapy has demonstrated to be effective in locally advanced mucinous colorectal cancer improving the oncological outcomes. However, this benefit could be diminished in high-risk stage II mucinous colon cancer patients. The administration of adjuvant chemotherapy on this patient's sub-group must be balanced according to risk versus benefits.

6.
Eur J Sport Sci ; 24(9): 1260-1269, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38949958

ABSTRACT

Change of directions (COD) involves multidirectional and complex actions, with performance influenced by multiple factors. As lower limb strength is one of the most determinant of COD performance, the present study aimed to (a) explore the differences in strength outcomes across different lower limb muscle actions between faster and slower basketball players in COD actions at different angles and (b) analyse the relationship between isometric, concentric and eccentric strength outcomes and COD performance at different cutting angles. Twenty-five basketball players (44% female) completed a battery of tests, encompassing isokinetic and isometric squat strength assessments, along with COD tests at 45°, 90° and 180°. Players were categorised as 'low-performance' and 'high-performance' groups based on execution time in COD, facilitating a comparison between performance groups. Results indicated that concentric strength showed the greatest differences between performance groups at 45° COD (effect size ≥ 0.813; p ≤ 0.034). Isometric and eccentric strength demonstrated a moderate-to-large relationship with 90° COD performance (Rho ≥ 0.394; p ≤ 0.045), and all muscle actions exhibited a large relationship with 180° COD (Rho ≥ 0.445; p ≤ 0.030). Moreover, the fastest players showed higher levels of concentric strength relative to eccentric strength, regardless of the cutting angle. These findings hold practical applications, suggesting that basketball coaches should train a specific kind of muscle action depending on the individual players' COD demands, focusing on improving the rapid eccentric force application while striving to reduce the eccentric/concentric ratio.


Subject(s)
Athletic Performance , Basketball , Lower Extremity , Muscle Strength , Humans , Basketball/physiology , Muscle Strength/physiology , Male , Female , Athletic Performance/physiology , Young Adult , Lower Extremity/physiology , Muscle, Skeletal/physiology , Isometric Contraction/physiology , Adult , Adolescent
8.
Mol Genet Genomic Med ; 12(7): e2496, 2024 Jul.
Article in English | MEDLINE | ID: mdl-39056403

ABSTRACT

BACKGROUND: Hereditary diffuse gastric cancer (HDGC) (OMIM# 137215) is an autosomal dominant cancer syndrome associated with CDH1 (OMIM# 192090) mutations. Prophylactic total gastrectomy (PTG) is the most recommended preventive treatment when a pathogenic mutation is found. However, the increasing use of genetic testing has led to the identification of incidental CDH1 mutations in individuals without a family history of gastric cancer. It remains unclear whether these patients should undergo prophylactic total gastrectomy. METHODS: Germline DNA, obtained from peripheral blood, was analysed by NGS. RESULTS: A 47-year-old woman was diagnosed with high-grade serous ovarian carcinoma, FIGO stage IIIC, with a Homologous Recombination Deficiency (HRD) GIS status of 78 (positive, cut-off: 43). She received chemotherapy and niraparib treatment. A multigene panel test revealed no pathogenic mutations in BRCA1 (OMIM# 113705)/BRCA2 (OMIM# 600185) genes, but a de novo deletion of exon 16 in CDH1 was found incidentally. She had no previous family history of gastric or breast cancer. The patient was enrolled in a surveillance program involving periodic endoscopy and was diagnosed with diffuse gastric cancer through biopsies of a pale area in the antrum after 1 year of close endoscopic follow-up. CONCLUSION: This case presents supportive evidence for the pathogenic classification of the loss of the last exon of CDH1.


Subject(s)
Antigens, CD , Cadherins , Ovarian Neoplasms , Stomach Neoplasms , Humans , Female , Middle Aged , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , Antigens, CD/genetics , Cadherins/genetics , Ovarian Neoplasms/genetics , Ovarian Neoplasms/pathology , Gastrectomy , Germ-Line Mutation
9.
Vaccines (Basel) ; 12(7)2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39066411

ABSTRACT

Following the development of a value of vaccination (VoV) framework for health technology assessment/cost-effectiveness analysis (HTA/CEA), and identification of three vaccination benefits for near-term inclusion in HTA/CEA, this final paper provides decision makers with methods and examples to consider benefits of health systems strengthening (HSS), equity, and macroeconomic gains. Expert working groups, targeted literature reviews, and case studies were used. Opportunity cost methods were applied for HSS benefits of rotavirus vaccination. Vaccination, with HSS benefits included, reduced the incremental cost-effectiveness ratio (ICER) by 1.4-50.5% (to GBP 11,552-GBP 23,016) depending on alternative conditions considered. Distributional CEA was applied for health equity benefits of meningococcal vaccination. Nearly 80% of prevented cases were among the three most deprived groups. Vaccination, with equity benefits included, reduced the ICER by 22-56% (to GBP 7014-GBP 12,460), depending on equity parameters. Macroeconomic models may inform HTA deliberative processes (e.g., disease impact on the labour force and the wider economy), or macroeconomic outcomes may be assessed for individuals in CEAs (e.g., impact on non-health consumption, leisure time, and income). These case studies show how to assess broader vaccination benefits in current HTA/CEA, providing decision makers with more accurate and complete VoV assessments. More work is needed to refine inputs and methods, especially for macroeconomic gains.

10.
J Enzyme Inhib Med Chem ; 39(1): 2377586, 2024 Dec.
Article in English | MEDLINE | ID: mdl-39037009

ABSTRACT

Species of Leishmania and Trypanosoma genera are the causative agents of relevant parasitic diseases. Survival inside their hosts requires the existence of a potent antioxidant enzymatic machinery. Four iron superoxide dismutases have been described in trypanosomatids (FeSODA, FeSODB1, FeSODB2, and FeSODC) that hold a potential as therapeutic targets. Nonetheless, very few studies have been developed that make use of the purified enzymes. Moreover, FeSODC remains uncharacterised in Leishmania. In this work, for the first time, we describe the purification and enzymatic activity of recombinant versions of the four Leishmania FeSOD isoforms and establish an improved strategy for developing inhibitors. We propose a novel parameter [(V*cyt. c - Vcyt. c)/Vcyt. c] which, in contrast to that used in the classical cytochrome c reduction assay, correlates linearly with enzyme concentration. As a proof of concept, we determine the IC50 values of two ruthenium carbosilane metallodendrimers against these isoforms.


Subject(s)
Antiprotozoal Agents , Dose-Response Relationship, Drug , Leishmania infantum , Parasitic Sensitivity Tests , Superoxide Dismutase , Leishmania infantum/enzymology , Leishmania infantum/drug effects , Structure-Activity Relationship , Molecular Structure , Superoxide Dismutase/metabolism , Superoxide Dismutase/antagonists & inhibitors , Superoxide Dismutase/chemistry , Antiprotozoal Agents/pharmacology , Antiprotozoal Agents/chemistry , Antiprotozoal Agents/chemical synthesis , Enzyme Inhibitors/pharmacology , Enzyme Inhibitors/chemistry , Enzyme Inhibitors/chemical synthesis , Leishmaniasis/drug therapy , Leishmaniasis/parasitology
11.
J Clin Invest ; 134(15)2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38861336

ABSTRACT

Reproduction is safeguarded by multiple, often cooperative, regulatory networks. Kisspeptin signaling, via KISS1R, plays a fundamental role in reproductive control, primarily by regulation of hypothalamic GnRH neurons. We disclose herein a pathway for direct kisspeptin actions in astrocytes that contributes to central reproductive modulation. Protein-protein interaction and ontology analyses of hypothalamic proteomic profiles after kisspeptin stimulation revealed that glial/astrocyte markers are regulated by kisspeptin in mice. This glial-kisspeptin pathway was validated by the demonstrated expression of Kiss1r in mouse astrocytes in vivo and astrocyte cultures from humans, rats, and mice, where kisspeptin activated canonical intracellular signaling-pathways. Cellular coexpression of Kiss1r with the astrocyte markers GFAP and S100-ß occurred in different brain regions, with higher percentage in Kiss1- and GnRH-enriched areas. Conditional ablation of Kiss1r in GFAP-positive cells in the G-KiR-KO mouse altered gene expression of key factors in PGE2 synthesis in astrocytes and perturbed astrocyte-GnRH neuronal appositions, as well as LH responses to kisspeptin and LH pulsatility, as surrogate marker of GnRH secretion. G-KiR-KO mice also displayed changes in reproductive responses to metabolic stress induced by high-fat diet, affecting female pubertal onset, estrous cyclicity, and LH-secretory profiles. Our data unveil a nonneuronal pathway for kisspeptin actions in astrocytes, which cooperates in fine-tuning the reproductive axis and its responses to metabolic stress.


Subject(s)
Astrocytes , Gonadotropin-Releasing Hormone , Kisspeptins , Mice, Knockout , Receptors, Kisspeptin-1 , Signal Transduction , Kisspeptins/metabolism , Kisspeptins/genetics , Animals , Astrocytes/metabolism , Mice , Receptors, Kisspeptin-1/metabolism , Receptors, Kisspeptin-1/genetics , Humans , Rats , Female , Gonadotropin-Releasing Hormone/metabolism , Gonadotropin-Releasing Hormone/genetics , Male , Hypothalamus/metabolism , Neurons/metabolism , Dinoprostone/metabolism , S100 Calcium Binding Protein beta Subunit/metabolism , S100 Calcium Binding Protein beta Subunit/genetics , Glial Fibrillary Acidic Protein/metabolism , Glial Fibrillary Acidic Protein/genetics , Reproduction
12.
ChemSusChem ; : e202400559, 2024 Jun 11.
Article in English | MEDLINE | ID: mdl-38860533

ABSTRACT

The ring-rearrangement of 5-hydroxymethylfurfural (HMF) to 3-hydroxymethylcyclopentanone (HCPN) was investigated over Ni catalysts supported on different carbon supports and metallic oxides with different structure and acid-base properties. Their catalytic performance was tested in a batch stirred reactor in aqueous solution at 180 °C and 30 bar of H2. Under these conditions, the HMF hydrogenation proceeds through three possible competitive routes: (i) a non-water path leading to the total hydrogenation product, 2,5-di-hydroxymethyl-tetrahydrofuran (DHMTHF), and two parallel acid-catalyzed water-mediated routes responsible for (ii) ring-opening and (iii) ring-rearrangement reaction products. All catalyst systems primarily produced HCPN, but reaction rates and product distribution were influenced by several variables, some of them intensely analyzed in this work. The most proper conditions resulted to be the presence of the medium/strong Lewis's acidity of a Ni/ZrO2 catalyst (initial TOF=5.99 min-1 and 73 % HCPN selectivity) or the Brønsted acidity originated by an oxidized high surface area graphite, Ni/HSAG-ox (initial TOF=5.92 min-1 and 87 % HCPN selectivity). However, too high density of acidic sites on the catalyst support (Ni/Al2O3) and sulfur impurities from the HMF feedstock led to catalyst deactivation by coke deposition and Ni poisoning, respectively.

13.
J Dent ; 146: 105067, 2024 07.
Article in English | MEDLINE | ID: mdl-38763385

ABSTRACT

OBJECTIVES: The aim of this study is to compare the aesthetic outcomes of metal porcelain (C), lithium disilicate (T1) and porcelain-layered zirconium (T2) immediate implant-supported single crowns in the anterior maxilla. MATERIALS AND METHODS: Forty-five immediate dental implants were provided for 45 patients that required the extraction of a single tooth in the anterior maxilla. A temporary prosthesis was provided at 8 weeks after placement followed by the final prosthesis at 24 weeks post-implantation. The patients were randomly allocated into 3 groups: 15 patients in the control group (C) received a metal-porcelain restoration, 15 patients (T1) received a lithium disilicate (LD) restoration and 15 patients (T2) received a porcelain-layered, zirconium (Z) restoration. Pink (PES) and White (WES) esthetic scores, radiographic bone levels, periodontal parameters and patient's esthetic satisfaction using a visual analogue scale (VAS) were evaluated at the time of final restoration placement (t0) and at 12-months post-loading (t12). RESULTS: No implants were lost during the duration of this study. Statistically significant higher WES and VAS scores (p < 0.05) were recorded in T1 vs C and T1 vs T2 groups respectively. Similar radiographic bone levels and periodontal parameters were recorded in all groups. CONCLUSION: Within the limitations of this study, it was concluded that T1 restorations provided better WES outcomes when compared to C restorations and better VAS scores when compared to T2 restorations at 12 months post-loading. Besides, different material interphases did not have an impact in PES, bone levels or periodontal parameters. CLINICAL RELEVANCE: There is limited data comparing aesthetic outcomes of implant supported single crowns made of different ceramic materials based on accepted and comparable indexes and the evaluation of the patient's perspective regarding these aesthetic outcomes.


Subject(s)
Crowns , Dental Implants, Single-Tooth , Dental Porcelain , Dental Prosthesis, Implant-Supported , Esthetics, Dental , Immediate Dental Implant Loading , Zirconium , Humans , Female , Male , Zirconium/chemistry , Dental Porcelain/chemistry , Adult , Middle Aged , Treatment Outcome , Patient Satisfaction , Dental Materials/chemistry , Maxilla/surgery , Metal Ceramic Alloys/chemistry , Dental Prosthesis Design , Young Adult
14.
Mol Oncol ; 2024 May 24.
Article in English | MEDLINE | ID: mdl-38790138

ABSTRACT

Pancreatic ductal adenocarcinoma (PDAC) is a highly lethal cancer, characterized by late diagnosis and poor treatment response. Surgery is the only curative approach, only available to early-diagnosed patients. Current therapies have limited effects, cause severe toxicities, and minimally improve overall survival. Understanding of splicing machinery alterations in PDAC remains incomplete. Here, we comprehensively examined 59 splicing machinery components, uncovering dysregulation in pre-mRNA processing factor 8 (PRPF8) and RNA-binding motif protein X-linked (RBMX). Their downregulated expression was linked to poor prognosis and malignancy features, including tumor stage, invasion and metastasis, and associated with poorer survival and the mutation of key PDAC genes. Experimental modulation of these splicing factors in pancreatic cancer cell lines reverted their expression to non-tumor levels and resulted in decreased key tumor-related features. These results provide evidence that the splicing machinery is altered in PDAC, wherein PRPF8 and RBMX emerge as candidate actionable therapeutic targets.

15.
Biol Proced Online ; 26(1): 13, 2024 May 15.
Article in English | MEDLINE | ID: mdl-38750435

ABSTRACT

BACKGROUND: Pseudomyxoma peritonei (PMP) is a rare peritoneal mucinous carcinomatosis with largely unknown underlying molecular mechanisms. Cytoreductive surgery combined with hyperthermic intraperitoneal chemotherapy is the only therapeutic option; however, despite its use, recurrence with a fatal outcome is common. The lack of molecular characterisation of PMP and other mucinous tumours is mainly due to the physicochemical properties of mucin. RESULTS: This manuscript describes the first protocol capable of breaking the mucin barrier and isolating proteins from mucinous tumours. Briefly, mucinous tumour samples were homogenised and subjected to liquid chromatography using two specific columns to reduce mainly glycoproteins, albumins and immunoglobulin G. The protein fractions were then subjected to mass spectrometry analysis and the proteomic profile obtained was analysed using various bioinformatic tools. Thus, we present here the first proteome analysed in PMP and identified a distinct mucin isoform profile in soft compared to hard mucin tumour tissues as well as key biological processes/pathways altered in mucinous tumours. Importantly, this protocol also allowed us to identify MUC13 as a potential tumour cell marker in PMP. CONCLUSIONS: In sum, our results demonstrate that this protein isolation protocol from mucin will have a high impact, allowing the oncology research community to more rapidly advance in the knowledge of PMP and other mucinous neoplasms, as well as develop new and effective therapeutic strategies.

16.
EMBO J ; 43(13): 2789-2812, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38811853

ABSTRACT

It has remained unknown how cells reduce cystine taken up from the extracellular space, which is a required step for further utilization of cysteine in key processes such as protein or glutathione synthesis. Here, we show that the thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) is the rate-limiting enzyme for intracellular cystine reduction. When TRP14 is genetically knocked out, cysteine synthesis through the transsulfuration pathway becomes the major source of cysteine in human cells, and knockout of both pathways becomes lethal in C. elegans subjected to proteotoxic stress. TRP14 can also reduce cysteinyl moieties on proteins, rescuing their activities as here shown with cysteinylated peroxiredoxin 2. Txndc17 knockout mice were, surprisingly, protected in an acute pancreatitis model, concomitant with activation of Nrf2-driven antioxidant pathways and upregulation of transsulfuration. We conclude that TRP14 is the evolutionarily conserved enzyme principally responsible for intracellular cystine reduction in C. elegans, mice, and humans.


Subject(s)
Caenorhabditis elegans , Cysteine , Cystine , Mice, Knockout , Oxidation-Reduction , Proteome , Thioredoxins , Animals , Humans , Mice , Caenorhabditis elegans/metabolism , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/metabolism , Caenorhabditis elegans Proteins/genetics , Cysteine/metabolism , Cystine/metabolism , Peroxiredoxins/metabolism , Peroxiredoxins/genetics , Proteome/metabolism , Thioredoxins/metabolism , Thioredoxins/genetics
17.
Emergencias (Sant Vicenç dels Horts) ; 36(2): 1-7, Abr. 2024. graf, tab
Article in Spanish | IBECS | ID: ibc-231797

ABSTRACT

Objetivos. Identificar factores pronósticos de desarrollo de síndrome neurológico tardío (SNT) después de un episodio inicial de intoxicación por monóxido de carbono (ICO), con el fin detectar precozmente a la población más susceptible y facilitar su acceso a un seguimiento específico. Métodos. Revisión retrospectiva de todos los casos de ICO que acudieron a los servicios de urgencias (SU) de 4 hospitales durante los últimos 10 años. Se analizaron datos demográficos y características clínicas en el momento del episodio. En la cohorte de pacientes con datos de seguimiento disponibles, se evaluó la aparición de SNT y su relación con diferentes variables en la exposición inicial al CO a través de técnicas de análisis multivariante. Resultados. Se identificaron 240 pacientes. La mediana de edad fue de 36,2 años (17,6-49,6). De ellos 108 (45,0%) eran hombres y 223 casos (92,9%) fueron accidentales. El nivel medio de COHb fue del 12,7% (6,2-18,7). En 44 (18,3%) episodios se disponía de datos de un seguimiento específico. En esta cohorte, 11 (25%) pacientes desarrollaron SNT. Una puntuación inicial más baja en la Escala Coma de Glasgow (GCS) (OR: 0,61, IC 95%: 0,41-0,92) fue predictor independiente del desarrollo del SNT, con un ABC en la curva COR de 0,876 (IC 95%: 0,761-0,990, p < 0,001). Conclusiones. Una puntuación inicial baja en la GCS parece ser un predictor clínico de desarrollo de SNT en la ICO. Dada la incidencia de SNT, consideramos fundamental establecer protocolos de seguimiento específico de estos pacientes tras su asistencia inicial en los SU. (AU)


Objectives. To identify predictors for developing delayed neurological syndrome (DNS) after an initial episode of carbon monoxide (CO) poisoning in the interest of detecting patients most likely to develop DNS so that they can be followed. Methods. Retrospective review of cases of CO poisoning treated in the past 10 years in the emergency departments of 4 hospitals in the AMICO study (Spanish acronym for the multicenter analysis of CO poisoning). We analyzed demographic characteristics of the patients and the clinical characteristics of the initial episode. The records of the cohort of patients with available follow-up information were reviewed to find cases of DNS. Data were analyzed by multivariant analysis to determine the relationship to characteristics of the initial exposure to CO. Results. A total of 240 cases were identified. The median (interquartile range) age of the patients was 36.2 years (17.6-49.6 years); 108 patients (45.0%) were men, and the poisoning was accidental in 223 cases (92.9%). The median carboxyhemoglobin concentration on presentation was 12.7% (6.2%-18.7%). Follow-up details were available for 44 patients (18.3%). Eleven of those patients (25%) developed DNS. A low initial Glasgow Coma Scale score predicted the development of DNS with an odds ratio (OR) of 0.61 (95% CI, 0.41-0.92) and an area under the receiver operating characteristic curve of 0.876 (95% CI, 0.761-0.990) (P <.001). Conclusions. The initial Glasgow Coma Scale score seems to be a clinical predictor of DNS after CO poisoning. We consider it important to establish follow-up protocols for patients with CO poisoning treated in hospital EDs. (AU)


Subject(s)
Humans , Carbon Monoxide Poisoning , Neurotoxicity Syndromes , Carboxyhemoglobin , Prognosis , Emergency Medical Services , Poisoning/mortality
18.
Emergencias ; 36(2): 116-122, 2024 Apr.
Article in Spanish, English | MEDLINE | ID: mdl-38597618

ABSTRACT

OBJECTIVES: To identify predictors for developing delayed neurological syndrome (DNS) after an initial episode of carbon monoxide (CO) poisoning in the interest of detecting patients most likely to develop DNS so that they can be followed. MATERIAL AND METHODS: Retrospective review of cases of CO poisoning treated in the past 10 years in the emergency departments of 4 hospitals in the AMICO study (Spanish acronym for the multicenter analysis of CO poisoning). We analyzed demographic characteristics of the patients and the clinical characteristics of the initial episode. The records of the cohort of patients with available follow-up information were reviewed to find cases of DNS. Data were analyzed by multivariant analysis to determine the relationship to characteristics of the initial exposure to CO. RESULTS: A total of 240 cases were identified. The median (interquartile range) age of the patients was 36.2 years (17.6-49.6 years); 108 patients (45.0%) were men, and the poisoning was accidental in 223 cases (92.9%). The median carboxyhemoglobin concentration on presentation was 12.7% (6.2%-18.7%). Follow-up details were available for 44 patients (18.3%). Eleven of those patients (25%) developed DNS. A low initial Glasgow Coma Scale score predicted the development of DNS with an odds ratio (OR) of 0.61 (95% CI, 0.41-0.92) and an area under the receiver operating characteristic curve of 0.876 (95% CI, 0.761-0.990) (P .001). CONCLUSION: The initial Glasgow Coma Scale score seems to be a clinical predictor of DNS after CO poisoning. We consider it important to establish follow-up protocols for patients with CO poisoning treated in hospital EDs.


OBJETIVO: Identificar factores pronósticos de desarrollo de síndrome neurológico tardío (SNT) después de un episodio inicial de intoxicación por monóxido de carbono (ICO), con el fin detectar precozmente a la población más susceptible y facilitar su acceso a un seguimiento específico. METODO: Revisión retrospectiva de todos los casos de ICO que acudieron a los servicios de urgencias (SU) de 4 hospitales durante los últimos 10 años. Se analizaron datos demográficos y características clínicas en el momento del episodio. En la cohorte de pacientes con datos de seguimiento disponibles, se evaluó la aparición de SNT y su relación con diferentes variables en la exposición inicial al CO a través de técnicas de análisis multivariante. RESULTADOS: Se identificaron 240 pacientes. La mediana de edad fue de 36,2 años (17,6-49,6). De ellos 108 (45,0%) eran hombres y 223 casos (92,9%) fueron accidentales. El nivel medio de COHb fue del 12,7% (6,2-18,7). En 44 (18,3%) episodios se disponía de datos de un seguimiento específico. En esta cohorte, 11 (25%) pacientes desarrollaron SNT. Una puntuación inicial más baja en la Escala Coma de Glasgow (GCS) (OR: 0,61, IC 95%: 0,41-0,92) fue predictor independiente del desarrollo del SNT, con un ABC en la curva COR de 0,876 (IC 95%: 0,761-0,990, p 0,001). CONCLUSIONES: Una puntuación inicial baja en la GCS parece ser un predictor clínico de desarrollo de SNT en la ICO. Dada la incidencia de SNT, consideramos fundamental establecer protocolos de seguimiento específico de estos pacientes tras su asistencia inicial en los SU.


Subject(s)
Carbon Monoxide Poisoning , Hyperbaric Oxygenation , Adult , Female , Humans , Male , Carbon Monoxide Poisoning/complications , Carbon Monoxide Poisoning/diagnosis , Carbon Monoxide Poisoning/therapy , Hyperbaric Oxygenation/methods , Retrospective Studies , Adolescent , Young Adult , Middle Aged
19.
Thromb Res ; 237: 94-99, 2024 May.
Article in English | MEDLINE | ID: mdl-38574519

ABSTRACT

BACKGROUND: Venous thromboembolism (VTE) is a critical complication after non-major trauma or surgery. While the risk and severity of VTE following major orthopedic surgery is well-documented, there is significant knowledge gap regarding, non-major trauma such as ankle sprains. METHODS: We analyzed data from the RIETE registry to assess the clinical characteristics, VTE prophylaxis usage, and outcomes in patients with VTE following ankle sprain versus those post elective knee arthroplasty. We aimed to assess the risk and severity of VTE in a population traditionally considered at lower risk. Risk stratification was performed using the TRiP(cast) score. RESULTS: Among 1,250 patients with VTE, those with ankle sprain (n = 459) were much younger than those post knee arthroplasty (n = 791), less often female, had fewer comorbidities, and received VTE prophylaxis less often (27% vs. 93 %). During anticoagulation, 26 patients developed recurrent VTE, 31 had major bleeding, and 12 died (fatal PE 3, fatal bleeding 2). There were no differences between the two groups in the rates of VTE recurrences (rate ratio (RR): 1.65; 95%CI: 0.69-3.88) or death (RR: 1.12; 95%CI: 0.33-3.46), but patients with VTE after ankle sprain had a lower rate of major bleeding (RR: 0.39; 95%CI: 0.13-0.99). CONCLUSIONS: Ankle sprain patients are often undertreated for VTE prophylaxis and have similar severity of VTE than those undergoing elective knee surgery, indicating the need for a more customized approach to VTE management.


Subject(s)
Ankle Injuries , Arthroplasty, Replacement, Knee , Venous Thromboembolism , Humans , Venous Thromboembolism/etiology , Venous Thromboembolism/prevention & control , Female , Male , Arthroplasty, Replacement, Knee/adverse effects , Middle Aged , Aged , Ankle Injuries/surgery , Ankle Injuries/complications , Adult , Risk Factors , Registries , Anticoagulants/therapeutic use
20.
FEBS Lett ; 2024 Apr 26.
Article in English | MEDLINE | ID: mdl-38676284

ABSTRACT

Ferroptosis is a unique form of cell death that was first described in 2012 and plays a significant role in various diseases, including neurodegenerative conditions. It depends on a dysregulation of cellular iron metabolism, which increases free, redox-active, iron that can trigger Fenton reactions, generating hydroxyl radicals that damage cells through oxidative stress and lipid peroxidation. Lipid peroxides, resulting mainly from unsaturated fatty acids, damage cells by disrupting membrane integrity and propagating cell death signals. Moreover, lipid peroxide degradation products can further affect cellular components such as DNA, proteins, and amines. In ischemic stroke, where blood flow to the brain is restricted, there is increased iron absorption, oxidative stress, and compromised blood-brain barrier integrity. Imbalances in iron-transport and -storage proteins increase lipid oxidation and contribute to neuronal damage, thus pointing to the possibility of brain cells, especially neurons, dying from ferroptosis. Here, we review the evidence showing a role of ferroptosis in ischemic stroke, both in recent studies directly assessing this type of cell death, as well as in previous studies showing evidence that can now be revisited with our new knowledge on ferroptosis mechanisms. We also review the efforts made to target ferroptosis in ischemic stroke as a possible treatment to mitigate cellular damage and death.

SELECTION OF CITATIONS
SEARCH DETAIL