Perceptual-Cognitive Skills of Basketball Referees: On-The-Court Visual Search Behavior.

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.

Analysis and relationship between the volume of upper limb lymphoedema and pressure pain threshold, neural range of motion, pain intensity, kinesiophobia, pain hypervigilance and catastrophizing in breast cancer survivors.

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.

Ventral hippocampal parvalbumin interneurons gate the acute anxiolytic action of the serotonergic psychedelic DOI.

There has been a recent renewal of interest in the therapeutic potential of serotonergic psychedelics. Here, we uncover the essential role of ventral hippocampus (vHpc) GABAergic interneurons in the anxiolytic effect evoked by the serotonergic psychedelic 2,5-dimethoxy-4-iodoamphetamine (DOI). Integrating anatomical, pharmacological, and genetic approaches, we show that 5-HT2A receptors in the CA1/subiculum (CA1/sub) region of the vHpc are required for the anxiolytic action of DOI. In vivo electrophysiology and opto-tagging experiments indicate that DOI enhances the firing rate of hippocampal fast-spiking parvalbumin (PV)-positive interneurons, most of which express the 5-HT2A receptors. Restoration of 5-HT2A receptors in PV-positive interneurons in a loss-of-function background reinstated the anxiolytic responses evoked by DOI in the vHpc CA1/sub region. Collectively, our results localize the acute anxiolytic action of a serotonergic psychedelic to 5-HT2A receptors in the ventral hippocampus and specifically identify PV-positive fast-spiking cells as a cellular trigger for the psychedelic-induced relief of anxiety-like behavior.

Do Preventive Programs Reduce the Need for New Sedations for the Treatment of Oral Pathologies in Healthy and Special Health Care Needs Children?

Background: The goal is to analyze the need for reinterventions under deep sedation to treat oral pathologies in a population of children with special health care needs (SHCNs) and healthy children who followed a prevention program and to study the influence of parental motivation and child collaboration on the need for reinterventions under deep sedation. Methods: A retrospective study was carried out in a private clinic in Cartagena (Murcia, Spain), with patients treated under deep sedation from 2006 to 2018, both years included, following the Strobe statement. Results: In this study with 230 children who were treated under deep sedation, 23.92% underwent two or more sedations. The mean time elapsed between the first and the second sedations was 21.64 ± 15.87 months, and the main cause for reinterventions was the occurrence of new pathologies. Significantly more pulp treatments were performed in the first sedation than in the second (p = 0.013) and in the third (p = 0.007). Healthy children required fewer reinterventions under deep sedation than children with special needs (6.42% vs. 39.67%). Similarly, patients who followed the preventive program and required some type of dental treatment were reoperated fewer times than those who did not follow the preventive program (35.8 vs. 50%); than "cooperative" children as opposed to "non-cooperative" (12.12% vs. 60.93%) and than patients with "motivated" parents as opposed to those with "non-motivated" parents (20.83% vs. 46.34%). A total of 50% of the children who participated in the preventive program became "cooperative", and 100% were able to receive some treatment in the dental chair. Conclusions: Prevention programs, including motivational interviewing, are essential to improve children's behavior in the dental chair and reduce the need for reinterventions under general anesthesia or deep sedation. Although patients with special needs do require more sedation during their lifetime due to their inability to cooperate, these programs are necessary for the maintenance of oral health status and for the early diagnosis of caries lesions. Pediatric dentists should implement a quarterly preventive program because it improves patient collaboration. It is essential to achieve the motivation of parents in the oral care of their children.

The mitochondrial Na+/Ca2+ exchanger NCLX is implied in the activation of hypoxia-inducible factors.

Eukaryotic cells and organisms depend on oxygen for basic living functions, and they display a panoply of adaptations to situations in which oxygen availability is diminished (hypoxia). A number of these responses in animals are mediated by changes in gene expression programs directed by hypoxia-inducible factors (HIFs), whose main mechanism of stabilization and functional activation in response to decreased cytosolic oxygen concentration was elucidated two decades ago. Human acute responses to hypoxia have been known for decades, although their precise molecular mechanism for oxygen sensing is not fully understood. It is already known that a redox component, linked with reactive oxygen species (ROS) production of mitochondrial origin, is implied in these responses. We have recently described a mechanism by which the mitochondrial sodium/calcium exchanger, NCLX, participates in mitochondrial electron transport chain regulation and ROS production in response to acute hypoxia. Here we show that NCLX is also implied in the response to hypoxia mediated by the HIFs. By using a NCLX inhibitor and interference RNA we show that NCLX activity is necessary for HIF-α subunits stabilization in hypoxia and for HIF-1-dependent transcriptional activity. We also show that hypoxic mitochondrial ROS production is not required for HIF-1α stabilization under all circumstances, suggesting that the basal cytosolic redox state or other mechanism(s) could be operating in the NCLX-mediated response to hypoxia that operates through HIF-α stabilization. This finding provides a link between acute and medium-term responses to hypoxia, reinforcing a central role of mitochondrial cell signalling in the response to hypoxia.

A hippocampal circuit mechanism to balance memory reactivation during sleep.

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.

Cost-benefit analysis of the National Immunization Program in Spain.

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.

Efficacy of systemic Chemotherapy on high-risk stage II and III Mucnious colon cancer. CHEMUCCA study part I.

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.

Strength characteristics in faster change of direction basketball players: A comparison across cutting angles.

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.

Capturing the Value of Vaccination within Health Technology Assessment and Health Economics-Practical Considerations for Expanding Valuation by Including Key Concepts.

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.

Clinical approach for managing patients with unexpected CDH1 mutations: A case report.

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.

The repertoire of iron superoxide dismutases from Leishmania infantum as targets in the search for therapeutic agents against leishmaniasis.

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.

Critical Factors Affecting the Selective Transformation of 5-Hydroxymethylfurfural to 3-Hydroxymethylcyclopentanone Over Ni Catalysts.

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.

Kisspeptin signaling in astrocytes modulates the reproductive axis.

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.

Aesthetic outcomes of different materials for delayed, single-tooth restorations for immediately placed implants. A randomized controlled clinical trial.

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.

Spliceosomic dysregulation in pancreatic cancer uncovers splicing factors PRPF8 and RBMX as novel candidate actionable targets.

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.

Breaking the Mucin Barrier: A New Affinity Chromatography-Mass Spectrometry Approach to Unveil Potential Cell Markers and Pathways Altered in Pseudomyxoma Peritonei.

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.

TRP14 is the rate-limiting enzyme for intracellular cystine reduction and regulates proteome cysteinylation.

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.

Caracterización clínica y factores predictivos de desarrollo de síndrome neurológico tardío en la intoxicación por monóxido de carbono: estudio AMICO / Clinical features and predictors of delayed neurological syndrome in carbon monoxide poisoning: the AMICO study

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)