Differences in early life cognitive function explain the association between low education and early dementia risk.

Major initiatives are currently attempting to prevent dementia by targeting modifiable risk factors. Low education is frequently pointed to as a potential key factor, due to its robust relationship with dementia risk. Impact of education is notoriously difficult to assess, however, because of associations with multiple other risk and protective factors, and large population-representative samples are required to tease the relationships apart. Here, we studied 207,814 Norwegian men born between 1950 and 1959 who underwent compulsory cognitive testing during military conscription as young adults, to systematically test associations of education, cognition, and other potentially important factors. While low education was associated with increased risk for dementia diagnosis (Hazard ratio [HR] = 1.37, CI: 1.17-1.60), this association was fully explained by earlier cognitive test scores (HR = 1.08, CI: .91-1.28). In contrast, low cognitive score was associated with double risk of later dementia diagnosis, even when taking education into account (HR = 2.00, CI: 1.65-2.42). This relationship survived controlling for early-life socioeconomic status and was replicated within pairs of brothers. The latter finding suggests that genetic and environmental factors shared within families, such as common genetics, parental education, childhood socioeconomic status, or other shared experiences, cannot account for the association. Rather, independent, non-familial factors are more important. In contrast, within-family factors accounted for the relationship between low education and diagnosis risk. In conclusion, implementing measures to increase cognitive function in childhood and adolescence appears to be a more promising strategy for reducing dementia burden.

Efficacy and safety of bendamustine-containing bridging therapy in R/R LBCL patients receiving CD19 CAR T-cells.

Bridging therapy (BT) after leukapheresis is required in most relapsed/refractory (R/R) large B-cell lymphoma (LBCL) patients receiving chimeric antigen receptor (CAR) T cells. Bendamustine-containing regimens are a potential BT option. We aimed to assess if this agent had a negative impact on CAR-T outcomes when it was administered as BT. We included R/R LBCL patients from six centers who received systemic BT after leukapheresis from February 2019 to September 2022; patients who only received steroids or had pre-apheresis bendamustine exposure were excluded. Patients were divided into two BT groups, with and without bendamustine. Separate safety and efficacy analyses were carried out for axi-cel and tisa-cel. Of 243 patients who received BT, bendamustine (benda) was included in 62 (26%). There was a higher rate of BT progressors in the non-benda group (62% vs. 45%, p = 0.02). Concerning CAR-T efficacy, complete responses were comparable for benda versus non-benda BT cohorts with axi-cel (70% vs. 53%, p = 0.12) and tisa-cel (44% vs. 36%, p = 0.70). Also, 12-month progression-free and overall survival were not significantly different between BT groups with axi-cel (56% vs. 43% and 71% vs. 63%) and tisa-cel (25% vs. 26% and 52% vs. 48%); there were no differences when BT response was considered. CAR T-cell expansion for each construct was similar between BT groups. Regarding safety, CRS G ≥3 (6% vs. 6%, p = 0.79), ICANS G ≥3 (15% vs. 17%, p = 0.68), severe infections, and neutropenia post-infusion were comparable among BT regimens. BT with bendamustine-containing regimens is safe for patients requiring disease control during CAR T-cell manufacturing.

A clinical practice guideline for the management of the foot and ankle in rheumatoid arthritis.

Rheumatoid arthritis causes progressive joint destruction in the long term, causing a deterioration of the foot and ankle. A clinical practice guideline has been created with the main objective of providing recommendations in the field of podiatry for the conservative management of rheumatoid arthritis. Thus, healthcare professionals involved in foot care of adults with rheumatoid arthritis will be able to follow practical recommendations. A clinical practice guideline was created including a group of experts (podiatrists, rheumatologists, nurses, an orthopaedic surgeon, a physiotherapist, an occupational therapist and patient with rheumatoid arthritis). Methodological experts using GRADE were tasked with systematically reviewing the available scientific evidence and developing the information which serves as a basis for the expert group to make recommendations. Key findings include the efficacy of chiropody in alleviating hyperkeratotic lesions and improving short-term pain and functionality. Notably, custom and standardized foot orthoses demonstrated significant benefits in reducing foot pain, enhancing physical function, and improving life quality. Therapeutic footwear was identified as crucial for pain reduction and mobility improvement, emphasizing the necessity for custom-made options tailored to individual patient needs. Surgical interventions were recommended for cases which were non-responsive to conservative treatments, aimed at preserving foot functionality and reducing pain. Moreover, self-care strategies and education were underscored as essential components for promoting patient independence and health maintenance. A series of recommendations have been created which will help professionals and patients to manage podiatric pathologies derived from rheumatoid arthritis.

Pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in bipolar disorder: A systematic review.

BACKGROUND: The various pharmacological interventions, ranging from mood stabilizers and antipsychotics to antidepressants, reflect the diff/iculty of treating depressive/manic symptomatology of bipolar disorder (BD). Among a broad range of mechanisms implicated, immune dysregulation may contribute to the increased inflammation that influences the course of BD. Inflammatory, neurotrophic and oxidative stress factors may be identified as promising peripheral biomarkers in brain functioning, perhaps serving as predictors of an effective response to treatment for BD. The present systematic review aimed to examine the evidence supporting the pharmacotherapeutic value of inflammatory and neurotrophic biomarkers in BD. METHODS: PubMed, PsychINFO, Scopus and Web of Science were searched from inception to May 2024 by two independent reviewers. A total of 40 studies with 3371 patients with diagnosis and intervention of BD were selected. RESULTS: Inconsistencies in the effects of pharmacological treatments on the connection between the expected anti-inflammatory response and symptomatologic improvement were identified. Mood stabilizers (lithium), antipsychotics (quetiapine), antidepressants (ketamine) or their combination were described to increase both pro-inflammatory (TNFα, IL-6) and anti-inflammatory (IL-4, IL-8) factors. Other medications, such as memantine and dextromethorphan, autoimmune (infliximab) non-steroidal anti-inflammatory (aspirin, celecoxib) drugs, antidiabetics (pioglitazone), and even dietary supplementation (omega-3), or their combination, clearly decrease inflammatory factors (TNFα, IL-6, IL-1ß, C-reactive protein) and/or increase the neurotrophic factor BDNF in BD patients. CONCLUSION: Inflammation in BD requires further investigation to understand the underlying immunologic mechanism, to identify predictors of treatment response, and to make informed decisions about the use and development of more effective pharmacological interventions for BD.

Standardisation of the definition of the types of oncological colectomy. Delphi method for consensus of experts of the Spanish association of surgeons.

There is no international consensus on the definition of the type of oncological resection that corresponds to each of the colectomies existing in the current literature. The objective is to define for each colectomy described in the literature: embryological dissection plane, vascular pedicles in which to perform central ligation, the extent of the colectomy, and the need for resection of the greater momentum. A consensus of experts is carried out through the Delphi methodology through two rounds from the Coloproctology Section of the Spanish Association of Surgeons. Study period: November 2021-January 2023. 120 experts were surveyed. Degrees of consensus: Very strong: >90%, Strong: 80-90%, Moderate: 50-80%, No consensus: <50%. The definition for each oncological colectomy was established by very strong, and strong recommendations. Each oncological colectomy was established as Right hemicolectomy (RHC), RHC with D3 lymphadenectomy, Extended-RHC, transverse colon segmental colectomy, splenic flexure segmental colectomy, subtotal colectomy, total colectomy, left hemicolectomy (LHC), extended-LHC, sigmoidectomy.

Assessing Predictive Value of SARS-CoV-2 Epitope-Specific CD8+ T-Cell Response in Patients with Severe Symptoms.

Specific T cell responses against SARS-CoV-2 provided an overview of acquired immunity during the pandemic. Anti-SARS-CoV-2 immunity determines the severity of acute illness, but also might be related to the possible persistence of symptoms (long COVID). We retrospectively analyzed ex vivo longitudinal CD8+ T cell responses in 26 COVID-19 patients diagnosed with severe disease, initially (1 month) and long-term (10 months), and in a cohort of 32 vaccinated healthcare workers without previous SARS-CoV-2 infection. We used peptide-human leukocyte antigen (pHLA) dextramers recognizing 26 SARS-CoV-2-derived epitopes of viral and other non-structural proteins. Most patients responded to at least one of the peptides studied, mainly derived from non-structural ORF1ab proteins. After 10 months follow-up, CD8+ T cell responses were maintained at long term and reaction against certain epitopes (A*01:01-ORF1ab1637) was still detected and functional, showing a memory-like phenotype (CD127+ PD-1+). The total number of SARS-CoV-2-specific CD8+ T cells was significantly associated with protection against long COVID in these patients. Compared with vaccination, infected patients showed a less effective immune response to spike protein-derived peptides restricted by HLA. So, the A*01:01-S865 and A*24:02-S1208 dextramers were only recognized in vaccinated individuals. We conclude that initial SARS-CoV-2-specific CD8+ T cell response could be used as a marker to understand the evolution of severe disease and post-acute sequelae after SARS-CoV-2 infection.

Reducing CLABSI through a quality strategy for the implementation of the aseptic non-touch technique in a pediatric ward.

BACKGROUND: Central line-associated bloodstream infections (CLABSIs) are among the most epidemiologically relevant health care-associated infections. The aseptic non-touch technique (ANTT) is a standardized practice used to prevent CLABSIs. In a pediatric hospital, the overall CLABSI rate was 1.92/1000 catheter days (CD). However, in one unit, the rate was 5.7/1000 CD. METHODS: Nurses were trained in ANTT. For the implementation, plan-do-study-act (PDSA) cycles were completed. Adherence monitoring of the ANTT and epidemiological surveillance were performed. RESULTS: ANTT adherence of 95% was achieved after 6 PDSA cycles. Hand hygiene and general cleaning reached 100% adherence. Port disinfection and material collection had the lowest adherence rates, with 76.2% and 84.7%, respectively. The CLABSI rate decreased from 5.7 to 1.26/1000 CD. CONCLUSION: The implementation of ANTT helped reduce the CLABSI rate. Training and continuous monitoring are key to maintaining ANTT adherence.

INTRODUCCIÓN: Las infecciones relacionadas con catéteres venosos centrales son unas de las infecciones asociadas a la atención de salud con mayor relevancia epidemiológica. La técnica aséptica «no tocar¼ es una práctica estandarizada que se utiliza para prevenir estas infecciones. En un hospital pediátrico, la tasa de infecciones relacionadas con catéteres venosos centrales fue de 1.92/1000 días de catéter. Sin embargo, en una de las unidades la tasa fue de 5.7/1000 días de catéter. MÉTODO: Se capacitaron enfermeras en la técnica aséptica «no tocar¼. Para la implementación se cumplieron ciclos de planificar-hacer-estudiar-actuar (PHEA). Se realizaron seguimiento de la adherencia a la técnica y vigilancia epidemiológica. RESULTADOS: Se logró una adherencia a la técnica aséptica «no tocar¼ del 95% después de seis ciclos. La higiene de manos y la limpieza general alcanzaron un 100% de cumplimiento. La desinfección de los puertos y la recolección de material alcanzaron la menor adherencia, con un 76.2% y un 84.7%, respectivamente. La tasa de infecciones relacionadas con catéteres venosos centrales disminuyó de 5.7 a 1.26 por 1000 días de catéter. CONCLUSIONES: La implementación de la técnica aséptica «no tocar¼ ayudó en la reducción de infecciones relacionadas con catéteres venosos centrales. La capacitación y el seguimiento continuo son clave para mantener el cumplimiento de la técnica.

Diet management in congenital diarrheas and enteropathies - general concepts and disease-specific approach, a narrative review.

Congenital diarrheas and enteropathies (CODE) are a group of rare, heterogenous, monogenic disorders that lead to chronic diarrhea in infancy. Definitive treatment is rarely available, and supportive treatment is the mainstay. Nutritional management in the form of either specialized formulas, restrictive diet, or parenteral nutrition support in CODE with poor enteral tolerance is the cornerstone of CODE treatment and long-term growth. The evidence to support the use of specific diet regimens and nutritional approaches in most CODE disorders is limited due to the rarity of these diseases and the scant published clinical experience. The goal of this review was to create a comprehensive guide for nutritional management in CODE, based on the currently available literature, disease mechanism, and the PediCODE group experience. Enteral diet management in CODE can be divided into 3 distinct conceptual frameworks: nutrient elimination, nutrient supplementation, and generalized nutrient restriction. Response to nutrient elimination or supplementation can lead to resolution or significant improvement in the chronic diarrhea of CODE and resumption of normal growth. This pattern can be seen in CODE due to carbohydrate malabsorption, defects in fat absorption, and occasionally in electrolyte transport defects. In contrast, general diet restriction is mainly supportive. However, occasionally it allows parenteral nutrition weaning or reduction over time, mainly in enteroendocrine defects and rarely in epithelial trafficking and polarity defects. Further research is required to better elucidate the role of diet in the treatment of CODE and the appropriate diet management for each disease.

Propionate and butyrate counteract renal damage and progression to chronic kidney disease.

BACKGROUND: Short-chain fatty acids (SCFAs), mainly acetate, propionate and butyrate, are produced by gut microbiota through fermentation of complex carbohydrates that cannot be digested by the human host. They affect gut health and can contribute at the distal level to the pathophysiology of several diseases, including renal pathologies. METHODS: SCFA levels were measured in chronic kidney disease (CKD) patients (n = 54) at different stages of the disease and associations with renal function and inflammation parameters were examined. The impact of propionate and butyrate in pathways triggered in tubular cells under inflammatory conditions was analysed using genome-wide expression assays. Finally, a pre-clinical mouse model of folic acid-induced transition from acute kidney injury to CKD was used to analyse the preventive and therapeutic potential of these microbial metabolites in the development of CKD. RESULTS: Faecal levels of propionate and butyrate in CKD patients gradually reduce as the disease progresses, and do so in close association with established clinical parameters for serum creatinine, blood urea nitrogen and the estimated glomerular filtration rate. Propionate and butyrate jointly downregulated the expression of 103 genes related to inflammatory processes and immune system activation triggered by TNF-α in tubular cells. In vivo, the administration of propionate and butyrate, either before or soon after injury, respectively prevented and slowed the progression of damage. This was indicated by a decrease in renal injury markers, the expression of pro-inflammatory and pro-fibrotic markers, and recovery of renal function over the long term. CONCLUSIONS: Propionate and butyrate levels are associated with a progressive loss of renal function in CKD patients. Early administration of these SCFAs prevents disease advancement in a pre-clinical model of acute renal damage, demonstrating their therapeutic potential independently of the gut microbiota.

Exploring kidney allograft rejection: A proof-of-concept study using spatial transcriptomics.

In this proof-of-concept study, spatial transcriptomics combined with public single-cell ribonucleic acid-sequencing data were used to explore the potential of this technology to study kidney allograft rejection. We aimed to map gene expression patterns within diverse pathologic states by examining biopsies classified across nonrejection, T cell-mediated acute rejection, interstitial fibrosis, and tubular atrophy. Our results revealed distinct immune cell signatures, including those of T and B lymphocytes, monocytes, mast cells, and plasma cells, and their spatial organization within the renal interstitium. We also mapped chemokine receptors and ligands to study immune cell migration and recruitment. Finally, our analysis demonstrated differential spatial enrichment of transcription signatures associated with kidney allograft rejection across various biopsy regions. Interstitium regions displayed higher enrichment scores for rejection-associated gene expression patterns than tubular areas, which had negative scores. This implies that these signatures are primarily driven by processes unfolding in the renal interstitium. Overall, this study highlights the value of spatial transcriptomics for revealing cellular heterogeneity and immune signatures in renal transplant biopsies and demonstrates its potential for studying the molecular and cellular mechanisms associated with rejection. However, certain limitations must be borne in mind regarding the development and future applications of this technology.

Respiratory viral coinfections in pediatric patients in the primary care setting: a multicenter prospective study within the COPEDICAT network.

Acute respiratory viral infections pose a significant healthcare burden on the pediatric population globally, but data on the dissemination pattern in the community due to the COVID-19 pandemic are scarce. We conducted a two-year prospective multicenter study in Catalonia (Spain) that examined the prevalence and coinfection dynamics of respiratory viruses among 1276 pediatric patients from different age groups attending primary care. Coinfection analysis demonstrated complex patterns and revealed a coinfection rate of 23.8% for SARS-CoV-2, often in association with rhinovirus or influenza A. This study provides valuable data to understand post-pandemic viral interactions, which is imperative for public health interventions.

Democratic quality and excess mortality during the COVID-19 pandemic.

The aim of this study is to analyse the relationship between democratic quality and excess mortality produced in the year 2020 before COVID-19 vaccinations were generalised. Using cross-sectional data from 80 countries on five continents, multiple linear regression models between excess mortality, the general democracy index and its disaggregation into five categories: electoral process and pluralism, government functioning, political participation, political culture and civil liberties were estimated. The analysis also considered, public health spending per capita, overweight inhabitants, the average temperature of the country, population over 65 years of age, The KOF Globalisation Index, and the Gross National Income per capita as control variables. It was possible to establish a strong inverse association between excess mortality per million inhabitants and the general democracy index and four of its five categories. There was a particularly strong relationship between excess mortality and the political culture dimension (-326.50, p < 0.001). The results suggest that the higher the democratic quality of the political institutions of a State and particularly of their political culture the more improved the response and management of the pandemic was in preventing deaths and protecting their citizens more effectively. Conversely, countries with lower democracy index values have higher excess mortality. Quality democratic political institutions provide more effective public health policies in the face of the COVID-19 pandemic.

Development of a scale to gain insight into the experience of living with chronic heart failure: The UNAV-Experience of Living with Chronic Heart Failure Scale.

BACKGROUND: To date, there are no tools for the nursing staff to gain systematic insight on the experience lived by patients with chronic heart failure. The objective of this study was to develop a scale for this purpose. METHODS: The study was conducted between January 2018 and December 2020 in three Spanish hospitals. The process described by DeVellis was used for the development of the scale. The items were built based on a phenomenological study and a systematic review of the literature. Next, feedback from a panel of experts was obtained, the scale was administered to a sample of patients with chronic heart failure, and a cognitive interview and an observational study were conducted to create the final version of the scale. RESULTS: The first version of the scale had in seven domains and 76 items. After its evaluation by a panel of experts, it was reduced to a second version with six domains and 55 items. Following the administration of Version 2 to 17 patients (58.8% male, mean age 59.53, 70.6% classified as NYHA functional class II), five items were modified and two eliminated. Thus, the third version of the UNAV-CHF Experience Scale was composed of six domains and 53 items. CONCLUSIONS: This study presents the development of the UNAV-experience of living with chronic heart failure scale. It is an original and novel instrument that allows systematically explore this experience. A larger-scale study is necessary to confirm the validity of our scale.

Numerical study of the scattering of acoustic waves by an elliptic vortex.

The scattering of the acoustic waves generated by a monopolar source propagating through a two-dimensional elliptic vortex, fixed or convected by a uniform flow, is studied by solving the Linearized Euler Equations in Cartesian coordinates using the Discontinuous Galerkin Method. For a fixed vortex position, the number, amplitudes, and angular spreads of the acoustic interference beams resulting from the sound scattering are found to significantly depend on the orientation of the vortex major axis with respect to the direction of the incident waves and on the vortex maximum tangential velocity. In particular, additional interference beams are obtained at large observation angles for a more elliptical vortex. For a convected elliptic vortex, the interference beams are curved as the angle between the incident acoustic wave and the vortex major axis varies when the vortex travels in the downstream direction. As expected, the scattering of the acoustic waves leads to spectral broadening in this case. Moreover, the widths and the frequencies of the lateral lobes obtained in the spectra on both sides of the peak at the source frequency are different for elliptic and round vortices.

BET inhibitor nanotherapy halts kidney damage and reduces chronic kidney disease progression after ischemia-reperfusion injury.

Targeting epigenetic mechanisms has emerged as a potential therapeutic approach for the treatment of kidney diseases. Specifically, inhibiting the bromodomain and extra-terminal (BET) domain proteins using the small molecule inhibitor JQ1 has shown promise in preclinical models of acute kidney injury (AKI) and chronic kidney disease (CKD). However, its clinical translation faces challenges due to issues with poor pharmacokinetics and side effects. Here, we developed engineered liposomes loaded with JQ1 with the aim of enhancing kidney drug delivery and reducing the required minimum effective dose by leveraging cargo protection. These liposomes efficiently encapsulated JQ1 in both the membrane and core, demonstrating superior therapeutic efficacy compared to freely delivered JQ1 in a mouse model of kidney ischemia-reperfusion injury. JQ1-loaded liposomes (JQ1-NPs) effectively targeted the kidneys and only one administration, one-hour after injury, was enough to decrease the immune cell (neutrophils and monocytes) infiltration to the kidney-an early and pivotal step to prevent damage progression. By inhibiting BRD4, JQ1-NPs suppress the transcription of pro-inflammatory genes, such as cytokines (il-6) and chemokines (ccl2, ccl5). This success not only improved early the kidney function, as evidenced by decreased serum levels of BUN and creatinine in JQ1-NPs-treated mice, along with reduced tissue expression of the damage marker, NGAL, but also halted the production of extracellular matrix proteins (Fsp-1, Fn-1, α-SMA and Col1a1) and the fibrosis development. In summary, this work presents a promising nanotherapeutic strategy for AKI treatment and its progression and provides new insights into renal drug delivery.

Dental color measurement to estimate age in adults: a systematic review and meta-analysis.

Age estimation is a major challenge in anthropology and forensic odontology laboratories, as well as in judicial settings, as one of the tools used in human identification. The aim of this study was to evaluate the usefulness of age estimation methods based on the accurate measurement of tooth color changes. A systematic review was carried out following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and in compliance with Cochrane criteria recommendations (PROSPERO registration number CRD 42022343371). An electronic search was performed in the following databases: Pubmed, Web of Science, Medline, Current Contents Connect, SciELO, KCI-Korean Journal Database, Derwent Innovations Index and Russian Citation Index. The search strategy yielded a total of 18 articles. A randomized meta-analysis model of the results for the CIE L*a*b* color variables stratified by age (less than 30 years, 30-60 years, 60 years and older) was performed with 9 of the 18 studies included in this systematic review. According to our results, sex and location of color measurement are the most influential factors in color estimation. All studies were carried out in healthy anterior teeth by spectrophotometry as the most commonly used method for color measurement, with CIE L*a*b* being the most commonly analyzed parameters. Studies based on age as a dependent variable showed R2 values between 0.28 and 0.56, being higher in ex vivo teeth. Studies based on age as an independent variable showed R2 values ranging from 0.10 to 0.48. The random model showed high heterogeneity for the L*, a* and b* parameters in all age groups, which is explained by discrepancies in age range and non-standardized conditions for color measurement. This systematic review highlights the need to protocolize age estimation studies that measure tooth color, in order to apply this method in different forensic settings.

Structural and functional comparisons of salivary α-glucosidases from the mosquito vectors Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus.

Mosquito vectors of medical importance both blood and sugar feed, and their saliva contains bioactive molecules that aid in both processes. Although it has been shown that the salivary glands of several mosquito species exhibit α-glucosidase activities, the specific enzymes responsible for sugar digestion remain understudied. We therefore expressed and purified three recombinant salivary α-glucosidases from the mosquito vectors Aedes aegypti, Anopheles gambiae, and Culex quinquefasciatus and compared their functions and structures. We found that all three enzymes were expressed in the salivary glands of their respective vectors and were secreted into the saliva. The proteins, as well as mosquito salivary gland extracts, exhibited α-glucosidase activity, and the recombinant enzymes displayed preference for sucrose compared to p-nitrophenyl-α-D-glucopyranoside. Finally, we solved the crystal structure of the Ae. aegypti α-glucosidase bound to two calcium ions at a 2.3 Ångstrom resolution. Molecular docking suggested that the Ae. aegypti α-glucosidase preferred di- or polysaccharides compared to monosaccharides, consistent with enzymatic activity assays. Comparing structural models between the three species revealed a high degree of similarity, suggesting similar functional properties. We conclude that the α-glucosidases studied herein are important enzymes for sugar digestion in three mosquito species.

Nanoparticle-Catalyzed Transamination under Tumor Microenvironment Conditions: A Novel Tool to Disrupt the Pool of Amino Acids and GSSG in Cancer Cells.

Catalytic cancer therapy targets cancer cells by exploiting the specific characteristics of the tumor microenvironment (TME). TME-based catalytic strategies rely on the use of molecules already present in the TME. Amino groups seem to be a suitable target, given the abundance of proteins and peptides in biological environments. Here we show that catalytic CuFe2O4 nanoparticles are able to foster transaminations with different amino acids and pyruvate, another key molecule present in the TME. We observed a significant in cellulo decrease in glutamine and alanine levels up to 48 h after treatment. In addition, we found that di- and tripeptides also undergo catalytic transamination, thereby extending the range of the effects to other molecules such as glutathione disulfide (GSSG). Mechanistic calculations for GSSG transamination revealed the formation of an imine between the oxo group of pyruvate and the free -NH2 group of GSSG. Our results highlight transamination as alternative to the existing toolbox of catalytic therapies.

Sensibilidad de la respuesta simpática cutánea y de la gammagrafía en el diagnóstico del síndrome dolor regional complejo / Sensitivity of the sympathetic skin response and scintigraphy in the diagnosis of complex regional pain syndrome

Objetivo: Evaluar la sensibilidad de la respuesta simpática cutánea (RSC) y compararla con la gammagrafía en pacientes con síndrome de dolor regional complejo diagnosticados según criterios de Budapest. Material y métodos: Se evaluó prospectivamente a 22 pacientes con síndrome de dolor regional complejo que acudieron al Servicio de Rehabilitación y Medicina Física entre enero-2018 y mayo-2022. La gammagrafía se consideró positiva si en la 1.a-2.a fase se apreció leve captación asimétrica y difusa, o cuando en la 3.a fase se apreció marcada captación periarticular del radioisótopo. La RSC era anormal si se observaba: a) ausencia de respuesta tras 20 estímulos; b) falta de habituación con permanencia de los estímulos mayor al 67,2%. Resultados: Edad 55,4±8,57 años. Síndrome de dolor regional complejo más frecuente en mujeres (90,9%), más común en miembros superiores (68,2%) que en inferiores (31,8%). En la RSC hemos observado respuesta normal (<67,2%) en 2 pacientes (11,1%), falta de RSC en 2 pacientes (11,1%) y falta de habituación (>67,2%) en 14 pacientes (77,8%). En total, 16 pacientes presentaron respuestas anormales o ausentes (88,8%). La sensibilidad diagnóstica de la gammagrafía es similar a la de la RSC (89,5 vs. 88,8%), sin diferencia estadística (p=0,6721). Conclusión: La Gammagrafía ha demostrado una sensibilidad similar a la RSC, aunque la simpleza, el bajo coste y la no invasividad de esta última técnica sugieren que podría ser más coste/efectiva y segura (no ionizante). La falta de habituación y la ausencia de respuesta podrían identificar patrones de respuesta y localizar la afectación en las vías aferente, central, eferente o post ganglionar.(AU)

Objective: To evaluate the sensitivity of sympathetic skin response (SSR) and compare it with scintigraphy in patients with complex regional pain syndrome diagnosed according to the Budapest criteria. Material and methods: Twenty-two patients with complex regional pain syndrome who attended the Rehabilitation and Physical Medicine Department between January-2018 and May-2022 have been prospectively evaluated. The scintigraphy was considered positive if in the 1st-2nd phase slight asymmetric and diffuse uptake was observed, or when in the 3rd phase marked periarticular radioisotope uptake was observed. SSR was abnormal if: a) no response after 20 stimuli; b) lack of habituation with permanence of the stimuli greater than 67.2%. Results: Age 55.4±8.57 years. Complex regional pain syndrome was more frequent in women (90.9%), more common in upper limbs (68.2%) than lower limbs (31.8%). In SSR, we have observed normal response (<67.2%) in 2 patients (11.1%), lack of SSR in 2 patients (11.1%) and lack of habituation (>67.2%) in 14 patients (77.8%). In total, 16 patients presented abnormal or absent responses (88.8%). The diagnostic sensitivity of scintigraphy is similar to that of SSR (89.5% vs 88.8%), with no statistical difference (P=.6721). Conclusion: Scintigraphy has shown similar sensitivity to SSR, although the simplicity, security, low cost, non-ionizing and non-invasiveness of the latter technique suggest that it could be more cost-effective. The lack of habituation and the absence of response could identify response patterns and localize the involvement in the afferent, central, efferent or post-ganglionic pathways.(AU)