Validación de test de flexión-relajación para definir un déficit lumbar con electrodos tetrapolares / Validation of the flexion-relaxation test to define a lumbar deficit with tetrapolar electrodes

Introducción y objetivo: Obtener un nuevo punto de corte (PC) para un test de flexión-relajación (FR) lumbar efectuado con electrodos (e.) tetrapolares, desde valores ya definidos con dispositivos bipolares.Materiales y métodosLa muestra del estudio consta de 47 pacientes en situación de incapacidad temporal por dolor lumbar (DL). Fueron evaluados mediante un test de dinamometría isométrica, una prueba cinemática y una valoración del fenómeno FR.Se plantean dos experimentos con curvas ROC. El primero, con 47 pacientes que efectuaron de modo consecutivo el test FR con ambos tipos de electrodos, utilizándose como variable de clasificación el punto de corte conocido para los e. bipolares (2,49uV). En el segundo, con los datos de la EMGs registrados con e. tetrapolares en 17 pacientes, se efectúa un test de DeLong que compara las 2 curvas ROC que construimos, por un lado, al clasificar la muestra desde pruebas de dinamometría y cinemática, y por el otro, al clasificarlos con los valores de la EMGs bipolar.ResultadosUn total de 34 pacientes completaron adecuadamente las valoraciones del primer experimento y 17 pacientes el segundo. El primer estudio arroja un punto de corte de 1,2uV, con un AUC del 87,7%; sensibilidad 84,2% y especificidad 80%. El segundo muestra un PC para los e. bipolares de 1,21uV (AUC 87,5%) y para los e. tetrapolares de 1,43 (AUC 82,5%) con un test de DeLong sin diferencias significativas entre ambas curvas (p>0,4065).ConclusionesLa metodología de validación con curvas ROC ha permitido obtener un nuevo PC para la prueba FR de modo práctico, simplemente simultaneando ambos test sobre el mismo grupo de pacientes hasta obtener una muestra significativa. (AU)

Introduction and objective: To obtain a new cut-off point (CP) for a lumbar flexion-relaxation (RF) test established with tetrapolar (e.) electrodes, from values already defined with bipolar devices.Materials and methodsThe study sample consists of 47 patients in a situation of temporary disability due to low back pain (DL). They were evaluated by means of an isometric dynamometry test, a kinematic test and an assessment of the FR phenomenon.Two experiments with ROC curves are proposed. The first, with 47 patients who consecutively performed the RF test with both types of electrodes, using the cut-off point (CP) known for the e. bipolar (2.49μV). In the second, with the EMG data recorded with e. tetrapolar in 17 patients, a DeLong test was performed that compares the 2 ROC curves that were constructed on the one hand, by classifying the sample from dynamometry and kinematic tests, and on the other, by classifying them with the bipolar EMG values.ResultsA total of 34 patients adequately completed the evaluations of the first experiment and 17 patients the second. The first study shows a cut-off point of 1.2μV, with an AUC of 87.7%; Sensitivity 84.2% and Specificity 80%. The second shows a PC for e. bipolars of 1.21μV (AUC 87.5%) and for e. tetrapolar values of 1.43 (AUC 82.5%) with a DeLong test without significant differences between both curves (p>0.4065).ConclusionsThe validation methodology with ROC curves has made it possible to obtain a new PC for the RF test in a practical way, simply by simultaneously performing both tests on the same group of patients until a significant sample is obtained. (AU)

52-Week Mid-term Efficacy of Tildrakizumab in Moderate-to-severe Psoriasis: A Real-life Multicenter Experience.

Tildrakizumab is an IL-23-inhibitor that has been approved to treat plaque psoriasis. However, few reports have become available on its efficacy profile in the real-world. Our objective was to study the mid-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the Spanish routine clinical practice setting. This was a retrospective multicenter study that included a total of 91 psoriatic patients on tildrakizumab. The mean Psoriasis Area and Severity Index (PASI) was 9.09 (SD, 5.30). The overall tildrakizumab survival rate was 93.47% for a mean treatment exposure of 30.18 weeks (SD, 16,57). No drug discontinuation was associated with drug tolerability, or adverse reactions. Absolute PASI ≤ 3 was reached by 91.3% and 96.5% of the patients on weeks 28 and 52, respectively. Response was not impacted by weight, age (> 65), metabolic syndrome, presence of arthritis, or previous number of biological therapies used. Based on our own experience tildrakizumab is an effective strategy to treat plaque psoriasis and difficult-to-treat-areas.

Modelos experimentales murinos en la esclerosis lateral amiotrófica. Puesta al día / Murine experimental models of amyotrophic lateral sclerosis: An update

Introducción: La esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa, progresiva y de etiología desconocida caracterizada por la degeneración de motoneuronas superiores e inferiores. Aproximadamente el 90% de los casos de ELA son esporádicos, mientras que el 10% restante se consideran familiares. Independientemente de si son familiares o esporádicas, los pacientes desarrollan una debilidad progresiva, atrofia muscular con espasticidad y contracturas. Por lo general, la esperanza de vida en los pacientes de ELA es de 2 a 5 años. Desarrollo: Los modelos in vivo han ayudado a explicar la etiología y la patogénesis, así como los mecanismos de la ELA. Sin embargo, estos mecanismos no están del todo esclarecidos aún, por lo que los modelos experimentales son fundamentales para continuar con el estudio de los mismos, así como para la búsqueda de posibles dianas terapéuticas. A pesar de que el 90% de los casos son esporádicos, la mayoría de los modelos utilizados hasta la actualidad para estudiar la patogénesis están basados en las mutaciones genéticas asociadas a la enfermedad familiar, lo que provoca que la patogénesis de la ELA esporádica no sea aún conocida. Por tanto, sería fundamental el estudio de la enfermedad en modelos basados en la enfermedad esporádica. Conclusión: En el presente artículo se han revisado los principales modelos experimentales, tanto genéticos como esporádicos, utilizados en el estudio de esta enfermedad, enfocándonos en los que se han desarrollado utilizando el roedor como plataforma experimental.(AU)

Introduction: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose aetiology is unknown. It is characterised by upper and lower motor neuron degeneration. Approximately 90% of cases of ALS are sporadic, whereas the other 10% are familial. Regardless of whether the case is familial or sporadic, patients will develop progressive weakness, muscle atrophy with spasticity, and muscle contractures. Life expectancy of these patients is generally 2–5 years after diagnosis. Development: In vivo models have helped to clarify the aetiology and pathogenesis of ALS, as well as the mechanisms of the disease. However, as these mechanisms are not yet fully understood, experimental models are essential to the continued study of the pathogenesis of ALS, as well as in the search for possible therapeutic targets. Although 90% of cases are sporadic, most of the models used to study ALS pathogenesis are based on genetic mutations associated with the familial form of the disease; the pathogenesis of sporadic ALS remains unknown. Therefore, it would be critical to establish models based on the sporadic form. Conclusion: This article reviews the main genetic and sporadic experimental models used in the study of this disease, focusing on those that have been developed using rodents.(AU)

Holotomography and atomic force microscopy: a powerful combination to enhance cancer, microbiology and nanotoxicology research.

Modern imaging strategies are paramount to studying living systems such as cells, bacteria, and fungi and their response to pathogens, toxicants, and nanomaterials (NMs) as modulated by exposure and environmental factors. The need to understand the processes and mechanisms of damage, healing, and cell survivability of living systems continues to motivate the development of alternative imaging strategies. Of particular interest is the use of label-free techniques (microscopy procedures that do not require sample staining) that minimize interference of biological processes by foreign marking substances and reduce intense light exposure and potential photo-toxicity effects. This review focuses on the synergic capabilities of atomic force microscopy (AFM) as a well-developed and robust imaging strategy with demonstrated applications to unravel intimate details in biomedical applications, with the label-free, fast, and enduring Holotomographic Microscopy (HTM) strategy. HTM is a technique that combines holography and tomography using a low intensity continuous illumination laser to investigate (quantitatively and non-invasively) cells, microorganisms, and thin tissue by generating three-dimensional (3D) images and monitoring in real-time inner morphological changes. We first review the operating principles that form the basis for the complementary details provided by these techniques regarding the surface and internal information provided by HTM and AFM, which are essential and complimentary for the development of several biomedical areas studying the interaction mechanisms of NMs with living organisms. First, AFM can provide superb resolution on surface morphology and biomechanical characterization. Second, the quantitative phase capabilities of HTM enable superb modeling and quantification of the volume, surface area, protein content, and mass density of the main components of cells and microorganisms, including the morphology of cells in microbiological systems. These capabilities result from directly quantifying refractive index changes without requiring fluorescent markers or chemicals. As such, HTM is ideal for long-term monitoring of living organisms in conditions close to their natural settings. We present a case-based review of the principal uses of both techniques and their essential contributions to nanomedicine and nanotoxicology (study of the harmful effects of NMs in living organisms), emphasizing cancer and infectious disease control. The synergic impact of the sequential use of these complementary strategies provides a clear drive for adopting these techniques as interdependent fundamental tools.

Gut bacteriome and mood disorders in women with PCOS.

STUDY QUESTION: How does the gut bacteriome differ based on mood disorders (MDs) in women with polycystic ovary syndrome (PCOS), and how can the gut bacteriome contribute to the associations between these two conditions? SUMMARY ANSWER: Women with PCOS who also have MDs exhibited a distinct gut bacteriome with reduced alpha diversity and a significantly lower abundance of Butyricicoccus compared to women with PCOS but without MDs. WHAT IS KNOWN ALREADY: Women with PCOS have a 4- to 5-fold higher risk of having MDs compared to women without PCOS. The gut bacteriome has been suggested to influence the pathophysiology of both PCOS and MDs. STUDY DESIGN, SIZE, DURATION: This population-based cohort study was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), which includes all women born in Northern Finland in 1966. Women with PCOS who donated a stool sample at age 46 years (n = 102) and two BMI-matched controls for each case (n = 205), who also responded properly to the MD criteria scales, were included. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 102 women with PCOS and 205 age- and BMI-matched women without PCOS were included. Based on the validated MD criteria, the subjects were categorized into MD or no-MD groups, resulting in the following subgroups: PCOS no-MD (n = 84), PCOS MD (n = 18), control no-MD (n = 180), and control MD (n = 25). Clinical characteristics were assessed at age 31 years and age 46 years, and stool samples were collected from the women at age 46 years, followed by the gut bacteriome analysis using 16 s rRNA sequencing. Alpha diversity was assessed using observed features and Shannon's index, with a focus on genera, and beta diversity was characterized using principal components analysis (PCA) with Bray-Curtis Dissimilarity at the genus level. Associations between the gut bacteriome and PCOS-related clinical features were explored by Spearman's correlation coefficient. A P-value for multiple testing was adjusted with the Benjamini-Hochberg false discovery rate (FDR) method. MAIN RESULTS AND THE ROLE OF CHANCE: We observed changes in the gut bacteriome associated with MDs, irrespective of whether the women also had PCOS. Similarly, PCOS MD cases showed a lower alpha diversity (Observed feature, PCOS no-MD, median 272; PCOS MD, median 208, FDR = 0.01; Shannon, PCOS no-MD, median 5.95; PCOS MD, median 5.57, FDR = 0.01) but also a lower abundance of Butyricicoccus (log-fold changeAnalysis of Compositions of Microbiomes with Bias Correction (ANCOM-BC)=-0.90, FDRANCOM-BC=0.04) compared to PCOS no-MD cases. In contrast, in the controls, the gut bacteriome did not differ based on MDs. Furthermore, in the PCOS group, Sutterella showed positive correlations with PCOS-related clinical parameters linked to obesity (BMI, r2=0.31, FDR = 0.01; waist circumference, r2=0.29, FDR = 0.02), glucose metabolism (fasting glucose, r2=0.46, FDR < 0.001; fasting insulin, r2=0.24, FDR = 0.05), and gut barrier integrity (zonulin, r2=0.25, FDR = 0.03). LIMITATIONS, REASONS FOR CAUTION: Although this was the first study to assess the link between the gut bacteriome and MDs in PCOS and included the largest PCOS dataset for the gut microbiome analysis, the number of subjects stratified by the presence of MDs was limited when contrasted with previous studies that focused on MDs in a non-selected population. WIDER IMPLICATIONS OF THE FINDINGS: The main finding is that gut bacteriome is associated with MDs irrespective of the PCOS status, but PCOS may also modulate further the connection between the gut bacteriome and MDs. STUDY FUNDING/COMPETING INTEREST(S): This research was funded by the European Union's Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Grant Agreement (MATER, No. 813707), the Academy of Finland (project grants 315921, 321763, 336449), the Sigrid Jusélius Foundation, Novo Nordisk Foundation (NNF21OC0070372), grant numbers PID2021-12728OB-100 (Endo-Map) and CNS2022-135999 (ROSY) funded by MCIN/AEI/10.13039/501100011033 and ERFD A Way of Making Europe. The study was also supported by EU QLG1-CT-2000-01643 (EUROBLCS) (E51560), NorFA (731, 20056, 30167), USA/NIH 2000 G DF682 (50945), the Estonian Research Council (PRG1076, PRG1414), EMBO Installation (3573), and Horizon 2020 Innovation Grant (ERIN, No. EU952516). The funders did not participate in any process of the study. We have no conflicts of interest to declare. TRIAL REGISTRATION NUMBER: N/A.

52-Week Mid-term Efficacy of Tildrakizumab in Moderate-to-severe Psoriasis: A Real-life Multicenter Experience.

Tildrakizumab is an IL-23-inhibitor that has been approved to treat plaque psoriasis. However, few reports have become available on its efficacy profile in the real-world. Our objective was to study the mid-term efficacy of tildrakizumab in patients with moderate-to-severe psoriasis in the Spanish routine clinical practice setting. This was a retrospective multicenter study that included a total of 91 psoriatic patients on tildrakizumab. The mean Psoriasis Area and Severity Index (PASI) was 9.09 (SD, 5.30). The overall tildrakizumab survival rate was 93.47% for a mean treatment exposure of 30.18 weeks (SD, 16.57). No drug discontinuation was associated with drug tolerability, or adverse reactions. Absolute PASI ≤3 was reached by 91.3% and 96.5% of the patients on weeks 28 and 52, respectively. Response was not impacted by weight, age (>65), metabolic syndrome, presence of arthritis, or previous number of biological therapies used. Based on our own experience tildrakizumab is an effective strategy to treat plaque psoriasis and difficult-to-treat-areas.

Factors affecting N-acetyl-ß-D-glucosaminidase as an indicator for mastitis detection in dairy sheep.

The study of new indirect methods for mastitis detection is of great relevance both at the economic level of the farm and dairies, and in terms of consumer health, and animal welfare. These methods help us to monitor the disease and speed up the decision-making process on treatment of the affected animal and the destination of the milk. The main aim of this work was to study the effect of intramammary infection and other non-infectious factors on the activity of the enzyme N-acetyl-ß-D-glucosaminidase (NAGase) in milk, in order to evaluate its use as an indicator for the early diagnosis of mastitis in sheep that could be less expensive, easier to measure and a better marker of inflammation or complementary to existing methods such as somatic cell count (SCC). Seven biweekly samplings were carried out, in which NAGase activity, SCC and milk were analyzed. Glands were classified according to their sanitary status based on the results of the SCC and bacteriological analysis. Non-infectious factors such as lactation stage, parity number and milking session had a statistically significant effect on NAGase values, finding the highest NAGase values at the onset and end of the study, in infectious mastitic glands of multiparous females and at morning milking. However, among the NAGase variation factors studied, the health status of the gland was the factor that caused the highest variation in enzyme levels, with infectious mastitic glands showing higher values than healthy glands. The predictive ability of NAGase was also studied by means of several logistic regression models, with the one that included NAGase together with lactation stage and parity obtaining the best results if sensitivity is to be prioritized, or the model that included NAGase, lactation stage, parity, milking and production if specificity is to be prioritized. From the results obtained, it can be concluded that the use of NAGase as an intramammary infection detection method in sheep can be useful when non-infectious factors that cause changes in the concentration of the enzyme are also considered.

Global cross-cultural validation of a brief measure for identifying potential suicide risk in 42 countries.

OBJECTIVES: This study aimed to examine the psychometric properties of the P4 suicide screener in a multinational sample. The primary goal was to evaluate the reliability and validity of the scale and investigate its convergent validity by analyzing its correlation with depression, anxiety, and substance use. STUDY DESIGN: The study design is a cross-sectional self-report study conducted across 42 countries. METHODS: A cross-sectional, self-report study was conducted in 42 countries, with a total of 82,243 participants included in the final data set. RESULTS: The study provides an overview of suicide ideation rates across 42 countries and confirms the structural validity of the P4 screener. The findings indicated that sexual and gender minority individuals exhibited higher rates of suicidal ideation. The P4 screener showed adequate reliability, convergence, and discriminant validity, and a cutoff score of 1 is recommended to identify individuals at risk of suicidal behavior. CONCLUSIONS: The study supports the reliability and validity of the P4 suicide screener across 42 diverse countries, highlighting the importance of using a cross-cultural suicide risk assessment to standardize the identification of high-risk individuals and tailoring culturally sensitive suicide prevention strategies.

Short-term impact of air pollution, noise and temperature on emergency hospital admissions in Madrid (Spain) due to liver and gallbladder diseases.

BACKGROUND: Very few epidemiological studies have explored the environmental and meteorological risk factors that influence liver diseases and gallbladder disorders, and no studies have addressed the specific case of Spain. METHODS: This is a retrospective ecological study conducted during 2013-2018. We analysed emergency admissions in the central area of the Region of Madrid for the following causes: Liver and gallbladder diseases (L&GB) (ICD-10: K70-K81); disorders of gallbladder (DGB) (ICD 10: K80-K81); liver disease (LD) (ICD 10: K70-K77); alcoholic liver disease (ALD) (ICD-10: K70); viral hepatitis (VH) (ICD10:B15-B19); and hepatic failure, not elsewhere classified (HFNS) (ICD-10: K72). Independent variables used: meteorological (maximum daily temperature (Tmax in °C), minimum daily temperature (Tmin in °C), and relative humidity (RH in %)); chemical air pollution (8-hO3, NO2, PM10, PM2.5 in µg/m3); and noise pollution (equivalent level of daily noise (Ld in dB(A)). Transformed variables: extreme heat in degrees (Theat); wet cold (WC); and high ozone. We fitted Poisson models, negative binomials and zero-inflated Poisson controlled for seasonality, day of the week, holidays, trend, and autoregressive trend. Based on these models, the percentage of cases attributable to statistically significant risk factors was then estimated. RESULTS: In L&GB emergency admissions daily noise is related to 4.4% (CI95%: 0.8 7.9) of admissions; NO2 to 2.9% (CI95%: 0.1 5.7) and wet cold to 0.2% (CI95%: 0.8 7.9). Heat wave temperature was only related to ALD. In addition, the wet cold association with L&GB is also related to HFNS attributing 1.0% (CI95%: 0.3 1.8) of admissions for this cause. CONCLUSIONS: Daily noise and NO2 are associated with more than 7% of urgent L&GB admissions. Both pollutants, are mainly emitted by road traffic. A reduction of traffic in cities would result in a reduction of emergency admissions due to this cause.

Citrobacter rodentium possesses a functional type II secretion system necessary for successful host infection.

Infectious diarrheal diseases are the third leading cause of mortality in young children, many of which are driven by Gram-negative bacterial pathogens. To establish successful host infections these pathogens employ a plethora of virulence factors necessary to compete with the resident microbiota, and evade and subvert the host defenses. The type II secretion system (T2SS) is one such conserved molecular machine that allows for the delivery of effector proteins into the extracellular milieu. To explore the role of the T2SS during natural host infection, we used Citrobacter rodentium, a murine enteric pathogen, as a model of human intestinal disease caused by pathogenic Escherichia coli such as Enteropathogenic and Enterohemorrhagic E. coli (EPEC and EHEC). In this study, we determined that the C. rodentium genome encodes one T2SS and 22 potential T2SS-secreted protein effectors, as predicted via sequence homology. We demonstrated that this system was functional in vitro, identifying a role in intestinal mucin degradation allowing for its utilization as a carbon source, and promoting C. rodentium attachment to a mucus-producing colon cell line. During host infection, loss of the T2SS or associated effectors led to a significant colonization defect and lack of systemic spread. In mice susceptible to lethal infection, T2SS-deficient C. rodentium was strongly attenuated, resulting in reduced morbidity and mortality in infected hosts. Together these data highlight the important role of the T2SS and its effector repertoire during C. rodentium pathogenesis, aiding in successful host mucosal colonization.

PM534, an Optimized Target-Protein Interaction Strategy through the Colchicine Site of Tubulin.

Targeting microtubules is the most effective wide-spectrum pharmacological strategy in antitumoral chemotherapy, and current research focuses on reducing main drawbacks: neurotoxicity and resistance. PM534 is a novel synthetic compound derived from the Structure-Activity-Relationship study on the natural molecule PM742, isolated from the sponge of the order Lithistida, family Theonellidae, genus Discodermia (du Bocage 1869). PM534 targets the entire colchicine binding domain of tubulin, covering four of the five centers of the pharmacophore model. Its nanomolar affinity and high retention time modulate a strikingly high antitumor activity that efficiently overrides two resistance mechanisms in cells (detoxification pumps and tubulin ßIII isotype overexpression). Furthermore, PM534 induces significant inhibition of tumor growth in mouse xenograft models of human non-small cell lung cancer. Our results present PM534, a highly effective new compound in the preclinical evaluation that is currently in its first human Phase I clinical trial.

Murine experimental models of amyotrophic lateral sclerosis: an update.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease whose aetiology is unknown. It is characterised by upper and lower motor neuron degeneration. Approximately 90% of cases of ALS are sporadic, whereas the other 10% are familial. Regardless of whether the case is familial o sporadic, patients will develop progressive weakness, muscle atrophy with spasticity, and muscle contractures. Life expectancy of these patients is generally 2 to 5 years after diagnosis. DEVELOPMENT: In vivo models have helped to clarify the aetiology and pathogenesis of ALS, as well as the mechanisms of the disease. However, as these mechanisms are not yet fully understood, experimental models are essential to the continued study of the pathogenesis of ALS, as well as in the search for possible therapeutic targets. Although 90% of cases are sporadic, most of the models used to study ALS pathogenesis are based on genetic mutations associated with the familial form of the disease; the pathogenesis of sporadic ALS remains unknown. Therefore, it would be critical to establish models based on the sporadic form. CONCLUSIONS: This article reviews the main genetic and sporadic experimental models used in the study of this disease, focusing on those that have been developed using rodents.

Randomised clinical trial of Class II ART restoration in primary teeth with and without retentive grooves after 12 months.

AIM: The aim of the study was to evaluate the survival of Class II ART (Atraumatic Restorative Treatment) restorations in primary molars using encapsulated glass ionomer in cavities with and without retentive grooves. A total of 293 Class II restorations were performed on primary molars by three trained operators, using ART hand instruments (SS White/Duflex, Rio de Janeiro, Brazil) and restored with EQUIA Fil (GC Corporation, Tokyo, Japan). One hundred eighty-seven children aged 3 to 7 years (mean age = 5.5) from two public schools located in Lima, Peru, were included in the study. The restorations were performed following the ART protocol, randomising the presence or absence of proximal retentions. Cavity cleaning and restoration times were recorded by the assistant using a digital chronometer. After 6 and 12 months, evaluations occurred following the ART criteria. Data were analysed using the Mann-Whitney, Chisquare and Fisher's exact tests, Kaplan-Meier survival and logarithmic range. The mean dmf-s of the participants was 21.6 (S.D. = 10.2). The mean times to clean the cavity and apply the restorative material were 5.4 and 6.6 minutes, respectively. Success rates after 6 and 12 months for restorations without retentive grooves were 90.3% and 77.2%, respectively; and with retentive grooves 95.9% and 91.8%, respectively. Statistically significant differences were found at the 12-month follow-up (p = 0.001). The proximal retentive grooves increased the survival rate of ART Class II restorations in primary teeth after 12 months of follow-up.

Association of tyrosine hydroxylase 01 (TH01) microsatellite and insulin gene (INS) variable number of tandem repeat (VNTR) with type 2 diabetes and fasting insulin secretion in Mexican population.

PURPOSE: A variable number of tandem repeats (VNTR) in the insulin gene (INS) control region may be involved in type 2 diabetes (T2D). The TH01 microsatellite is near INS and may regulate it. We investigated whether the TH01 microsatellite and INS VNTR, assessed via the surrogate marker single nucleotide polymorphism rs689, are associated with T2D and serum insulin levels in a Mexican population. METHODS: We analyzed a main case-control study (n = 1986) that used univariate and multivariate logistic regression models to calculate the risk conferred by TH01 and rs689 loci for T2D development; rs689 results were replicated in other case-control (n = 1188) and cross-sectional (n = 1914) studies. RESULTS: TH01 alleles 6, 8, 9, and 9.3 and allele A of rs689 were independently associated with T2D, with differences between sex and age at diagnosis. TH01 alleles with ≥ 8 repeats conferred an increased risk for T2D in males compared with ≤ 7 repeats (odds ratio, ≥ 1.46; 95% confidence interval, 1.1-1.95). In females, larger alleles conferred a 1.5-fold higher risk for T2D when diagnosed ≥ 46 years but conferred protection when diagnosed ≤ 45 years. Similarly, rs689 allele A was associated with T2D in these groups. In males, larger TH01 alleles and the rs689 A allele were associated with a significant decrease in median fasting plasma insulin concentration with age in T2D cases; the reverse occurred in controls. CONCLUSION: Larger TH01 alleles and rs689 A allele may potentiate insulin synthesis in males without T2D, a process disabled in those with T2D.

[Validation of the flexion-relaxation test to define a lumbar deficit with tetrapolar electrodes]. / Validación de test de flexión-relajación para definir un déficit lumbar con electrodos tetrapolares.

INTRODUCTION AND OBJECTIVE: To obtain a new cut-off point (CP) for a lumbar flexion-relaxation (RF) test established with tetrapolar (e.) electrodes, from values already defined with bipolar devices. MATERIALS AND METHODS: The study sample consists of 47 patients in a situation of temporary disability due to low back pain (DL). They were evaluated by means of an isometric dynamometry test, a kinematic test and an assessment of the FR phenomenon. Two experiments with ROC curves are proposed. The first, with 47 patients who consecutively performed the RF test with both types of electrodes, using the cut-off point (CP) known for the e. bipolar (2.49µV). In the second, with the EMG data recorded with e. tetrapolar in 17 patients, a DeLong test was performed that compares the 2 ROC curves that were constructed on the one hand, by classifying the sample from dynamometry and kinematic tests, and on the other, by classifying them with the bipolar EMG values. RESULTS: A total of 34 patients adequately completed the evaluations of the first experiment and 17 patients the second. The first study shows a cut-off point of 1.2µV, with an AUC of 87.7%; Sensitivity 84.2% and Specificity 80%. The second shows a PC for e. bipolars of 1.21µV (AUC 87.5%) and for e. tetrapolar values of 1.43 (AUC 82.5%) with a DeLong test without significant differences between both curves (p>0.4065). CONCLUSIONS: The validation methodology with ROC curves has made it possible to obtain a new PC for the RF test in a practical way, simply by simultaneously performing both tests on the same group of patients until a significant sample is obtained.

Hepatitis C virus-positive donors in HCV-negative recipients in liver transplantation: Is it possible in Mexico?

Hepatitis C virus (HCV) infection is a worldwide public health problem associated with significant morbidity and mortality. In the context of liver transplantation, the demand for organs continues to exceed the supply, prompting the consideration of using organs from HCV-positive donors in HCV-negative recipients. The introduction of direct-acting antivirals (DAAs), which have demonstrated great efficacy in eradicating the virus, has made transplantation of organs from donors with HCV infection possible. The present article provides a brief review of the current evidence on the use of organs from HCV-infected patients.

Tannic Acid and Ethyl Gallate Potentialize Paclitaxel Effect on Microtubule Dynamics in Hep3B Cells.

Among broad-spectrum anticancer agents, paclitaxel (PTX) has proven to be one of the most effective against solid tumors for which more specific treatments are lacking. However, drawbacks such as neurotoxicity and the development of resistance reduce its therapeutic efficacy. Therefore, there is a need for compounds able to improve its activity by synergizing with it or potentiating its effect, thus reducing the doses required. We investigated the interaction between PTX and tannins, other compounds with anticancer activity known to act as repressors of several proteins involved in oncological pathways. We found that both tannic acid (TA) and ethyl gallate (EG) strongly potentiate the toxicity of PTX in Hep3B cells, suggesting their utility in combination therapy. We also found that AT and EG promote tubulin polymerization and enhance the effect of PTX on tubulin, suggesting a direct interaction with tubulin. Biochemical experiments confirmed that TA, but not EG, binds tubulin and potentiates the apparent binding affinity of PTX for the tubulin binding site. Furthermore, the molecular docking of TA to tubulin suggests that TA can bind to two different sites on tubulin, one at the PTX site and the second at the interface of α and ß-tubulin (cluster 2). The binding of TA to cluster 2 could explain the overstabilization in the tubulin + PTX combinatorial assay. Finally, we found that EG can inhibit PTX-induced expression of pAkt and pERK defensive protein kinases, which are involved in resistance to PXT, by limiting cell death (apoptosis) and favoring cell proliferation and cell cycle progression. Our results support that tannic acid and ethyl gallate are potential chemotherapeutic agents due to their potentiating effect on paclitaxel.

Evolution of physico-chemical parameters, microorganism diversity and volatile organic compound of apple pomace exposed to ambient conditions.

In apple processing, waste material known as apple pomace amounts to 45% of production volumes. When this residue is stored in open-air for its stabilization and potential uses, Volatile Organic Compounds (VOCs) are produced, resulting in environmental and odor pollution, and must be managed to avoid their impact. This work aims to study the emission of VOCs utilizing TD-GC/MS and its relationship with changes in physico-chemical (moisture, pH, proteins, among others) and biological (bacteria and fungi using Illumina MiSeq) parameters under three environmental conditions: open-air (outdoors), under-roof (indoors) and oxygen-free. The 8-month study results showed a gradual increase in odorous VOCs and microbial diversity, a product of chemical and biological transformation processes in the samples. A 30% increase in odorant compounds responsible for the unpleasant smell was observed, especially esters, aldehydes and hydrocarbons in samples stored in oxygen-free and Open-air conditions. Increases in VOCs over time were associated with changes in physico-chemical and biological parameters, as well as fluctuations in environmental variables (temperature, relative humidity, and precipitation). The results of this research allow establishing a relationship between storage conditions and the production of VOCs. In addition, recommendations for waste storage time are provided for the most common uses of apple pomace based on the physico-chemical parameters observed, in order to avoid the generation of odorous compounds. Of all storage methods analyzed, under-roof is the most adequate in practice. This study's findings are pertinent for managing agribusiness waste and its potential environmental pollution.

Characterization of texturized meat analogues containing native lupin flour and lupin protein concentrate/isolate.

Lupin is a nutritious, yet undervalued grain used as a fodder and food crop. In the present study, native lupin flour (LF), lupin protein concentrate (LPC), and lupin protein isolate (LPI) were combined (70% LPI:LPC blend ratios [30:70, 50:50, and 70:30] and 30% LF constant fraction), extruded at high moisture (45-55%), and shaped with a long cooling die (800 mm) to obtain texturized meat analogues (TMAs) with fibrous structures. The characteristics of TMAs (e.g., hardness, water hydration capacity) depended heavily on water content, blend ratios (LPI:LPC), and to a lesser extent, the long cooling die temperature. Color changes (i.e., L*, b*) were mostly attributed to variations in blend ratios (LPI:LPC). Microstructure analysis showed that TMAs with higher water content (55%) were more likely to have thinner walls and smaller void thickness. Fluorescence imagery revealed that TMAs with lower LPI content presented more homogeneous structures. These findings show that reasonable amounts (30% d.m.) of native lupin flour can be incorporated into meat analogues by maintaining a sufficiently high protein content (>50% d.m.) to trigger the formation of fibrous structures.

Comparison of round and knife-edge-like cathodes on gas-puff implosions.

Preionization is believed to play an important role on the implosion of gas-puff Z pinches. Some experiments have used an external preionization source, e.g., UV light or electron beam. In contrast, other experiments rely completely on over voltage breakdown by the own generator's voltage pulse. However, this approach lacks shot-to-shot reproducibility since self-breakdown is mainly a stochastic process. In this work, we performed a systematic study on self-breakdown using two different cathode geometries: (i) a smooth, round cathode to provide a homogeneous electric field, (ii) a sharp, knife-edge-like geometry to enhance the electric field locally and eventually electron emission. The experiments were carried out on the Llampudken current generator, which provides a current pulse of ∼400kA amplitude and 200 ns rise time (10%-90%). We implemented gated XUV imaging, filtered diodes and time-integrated x-ray imaging to obtain information about the implosion as well as the stagnation phase for the two cathode geometries. We found that erosion of the knife-edge cathode might be a serious problem, and we had to replace it every 15 shots. On the other hand, the round cathode lasted for the whole series of experiments. We also measured a more reproducible and larger peak current for the knife cathode. From the photo-conductive detectors we observed that even if the round cathode might present shots with higher x-ray yield compared to the knife cathode, dispersion is almost twice as large. Moreover, after a statistic analysis, it is demonstrated that the dispersion in the yield is due solely to differences imposed by the cathodes and not to variations in the driver, as no correlation was found between them. We found that in order to fit the experimental data with the snowplow model, only ∼60% of the total mass is compressed in the knife cathode while ∼20% for the round one, highlighting the importance of the cathode and preionization. Therefore, we conclude that the use of the knife cathode increases the reproducibility of the experiment in comparison with the round cathode.