Protein Hydrolysis as a Way to Valorise Squid-Processing Byproducts: Obtaining and Identification of ACE, DPP-IV and PEP Inhibitory Peptides.

The industrial processing of Argentine shortfin squid to obtain rings generates a significant amount of protein-rich waste, including the skin, which is rich in collagen and attached myofibrillar proteins. This waste is generally discarded. In this study, skin was used as a source of proteins that were hydrolysed using Trypsin, Esperase® or Alcalase®, which released peptides with antioxidant potential and, in particular, antihypertensive (ACE inhibition), hypoglycemic (DPP-IV inhibition) and/or nootropic (PEP inhibition) potential. Among the three enzymes tested, Esperase® and Alcalase produced hydrolysates with potent ACE-, DPP-IV- and PEP-inhibiting properties. These hydrolysates underwent chromatography fractionation, and the composition of the most bioactive fractions was analysed using HPLC-MS-MS. The fractions with the highest bioactivity exhibited very low IC50 values (16 and 66 µg/mL for ACE inhibition, 97 µg/mL for DPP-IV inhibition and 55 µg/mL for PEP inhibition) and were mainly derived from the hydrolysate obtained using Esperase®. The presence of Leu at the C-terminal appeared to be crucial for the ACE inhibitory activity of these fractions. The DPP-IV inhibitory activity of peptides seemed to be determined by the presence of Pro or Ala in the second position from the N-terminus, and Gly and/or Pro in the last C-terminal positions. Similarly, the presence of Pro in the peptides present in the best PEP inhibitory fraction seemed to be important in the inhibitory effect. These results demonstrate that the skin of the Argentine shortfin squid is a valuable source of bioactive peptides, suitable for incorporation into human nutrition as nutraceuticals and food supplements.

Cultural adaptation to Bolivian Quechua and psychometric analysis of the Patient Health Questionnaire PHQ-9.

OBJECTIVE: Cultural adaptation of the Patient Health Questionnaire-PHQ-9 to Bolivian Quechua and analysis of the internal structure validity, reliability, and measurement invariance by sociodemographic variables. METHODS: The PHQ-9 was translated and back-translated (English-Quechua-English) to optimise translation. For the cultural adaptation, experts, and people from the target population (e.g., in focus groups) verified the suitability of the translated PHQ-9. For the psychometric analysis, we performed a Confirmatory Factor Analysis (CFA) to evaluate internal validity, calculated α and ω indices to assess reliability, and performed a Multiple Indicator, Multiple Cause (MIMIC) model for evaluating measurement invariance by sex, age, marital status, educational level and residence. We used standard goodness-of-fit indices to interpret both CFA results. RESULTS: The experts and focus groups improved the translated PHQ-9, making it clear and culturally equivalent. For the psychometric analysis, we included data from 397 participants, from which 73.3% were female, 33.0% were 18-30 years old, 56.7% reported primary school studies, 63.2% were single, and 62.0% resided in urban areas. In the CFA, the single-factor model showed adequate fit (Comparative Fit Index = 0.983; Tucker-Lewis Index = 0.977; Standardized Root Mean Squared Residual = 0.046; Root Mean Squared Error of Approximation = 0.069), while the reliability was optimal (α = 0.869-0.877; ω = 0.874-0.885). The invariance was confirmed across all sociodemographic variables (Change in Comparative Fit Index (delta) or Root Mean Square Error of Approximation (delta) < 0.01). CONCLUSIONS: The PHQ-9 adapted to Bolivian Quechua offers a valid, reliable and invariant unidimensional measurement across groups by sex, age, marital status, educational level and residence.

Differences in family functioning before and during the COVID-19 pandemic: an observational study in Peruvian families.

The COVID-19 pandemic has had a major impact on family relationships, as several families have lost family members due to COVID-19 pandemic and become physically and emotionally estranged due to lockdown measures and critically economic periods. Our study contrasted two hypotheses: (1) family functioning changed notably before and after the COVID-19 pandemic initiation in terms of cohesion, flexibility, communication and satisfaction; (2) balanced families have a greater capacity to strictly comply with quarantine (i.e., social confinement), compared to unbalanced families. We performed an observational study comparing family functioning between two independent groups, evaluated before and during the first wave of the COVID-19 pandemic in Peru. A total of 7,980 participants were included in the study. For the first hypothesis, we found that, during the pandemic, families became more balanced in terms of cohesion (adjusted before-during mean difference or ß1 = 1.4; 95% CI [1.0-1.7]) and flexibility (ß2 = 2.0; 95% CI [1.6-2.4]), and families were less disengaged (ß3 = -1.9; 95% CI [-2.3 to -1.5]) and chaotic (ß4 = -2.9; 95% CI [-3.3 to -2.4]). Regarding the second hypothesis, we confirmed that families with balanced cohesion (adjusted prevalence ratio or aPR = 1.16; 95% CI [1.12-1.19) and flexibility (aPR = 1.23; 95% CI [1.18-1.27]) allowed greater compliance with quarantine restrictions; while disengaged (aPR = 0.91; 95% CI [0.88-0.93]) and chaotic families (aPR = 0.89; 95% CI [0.87-0.92]) were more likely to partially comply or not comply with the quarantine. Finally, family communication (aPR = 1.17; 95% CI [1.11-1.24]) and satisfaction (aPR = 1.18; 95% CI [1.11-1.25]) also played a role in favouring quarantine compliance. This new evidence enlightens the family systems theory while informing future interventions for improving compliance with quarantine measures in the context of social confinement.

Self-expanding Metal Stents in Malignant Obstruction of the Esophagus: A 25-Year Multicentric Study

Background: Self-expanding metal prostheses improve dysphagia in patients with incurable esophageal cancer (EC). New stents have been introduced, and chemoradiotherapy has been implemented for EC, changing patients' risk profiles. It is unknown whether this has affected palliation with stents. Patients and methods: Retrospective study in three centers in Medellín-Colombia; patients undergoing placement of palliative esophageal prostheses for malignant dysphagia (1997-2022). Major and minor complications after implantation, the influence of oncological therapies, and survival were evaluated for 1997-2009 (n = 289) and 2010-2022 (n = 318). Results: 607 patients underwent esophageal prostheses; 296 (48.8%) became complicated. It was higher in the second period (52.5% vs. 48.1%), as were major complications (20.8% vs. 14.2%, p = 0.033), with no differences in minor complications (33.9% vs 31.8%, p = 0.765). Also, 190 (31.3%) patients presented with recurrent dysphagia, stable in both periods. Migration increased over time (from 13.1% to 18.2%, p = 0.09). The most common minor adverse event was pain, increasing over time (from 24.9% to 33.95%, p < 0.01), and associated factors were chemoradiotherapy, absence of fistula, and squamous cell carcinoma. Acid reflux decreased in the second group (p = 0.038). Twelve percent of patients required another intervention for feeding. Survival was not impacted by time and use of stents. Conclusions: Stents are an alternative in non-surgical malignant dysphagia, although recurrent dysphagia has not decreased over time. Minor stent-related complications are increasing in association with the implementation of chemoradiotherapy.

Antecedentes: Las prótesis metálicas autoexpandibles mejoran la disfagia en pacientes con cáncer esofágico (CE) incurable. En las últimas décadas se han introducido nuevos tipos de stents y se ha implementado la quimiorradioterapia para el CE, generando cambios en los perfiles de riesgo de los pacientes. Se desconoce si estos cambios han afectado la paliación con stents. Pacientes y métodos: Estudio retrospectivo en tres centros de Medellín-Colombia; pacientes sometidos a colocación de prótesis esofágicas paliativas para disfagia maligna (1997-2022). Se evaluaron en dos períodos: 1997-2009 (n = 289) y 2010-2022 (n = 318), complicaciones mayores y menores después del implante, la influencia de las terapias oncológicas y la sobrevida. Resultados: Se evaluaron 607 pacientes sometidos a prótesis esofágicas. 296 (48,8%) se complicaron, y fue mayor en el segundo periodo (52,5% frente a 48,1%), al igual que las complicaciones mayores (20,8% frente a 14,2%, p = 0,033), sin diferencias en complicaciones menores (33,9% frente a 31,8%, p = 0,765). 190 (31,3%) pacientes presentaron disfagia recurrente, estable en ambos períodos. La migración aumentó con el tiempo (de 13,1% a 18,2%, p = 0,09). El evento adverso menor más frecuente fue dolor, que aumentó con el tiempo (de 24,9% a 33,95%, p < 0,01), y los factores asociados fueron quimiorradioterapia, ausencia de fístula y carcinoma de células escamosas. El reflujo ácido disminuyó en el segundo grupo (p = 0,038). El 12% de pacientes requirieron otra intervención para alimentarse. No se impactó la sobrevida con el tiempo y uso de stents. Conclusiones: Los stents son una alternativa en la disfagia maligna no quirúrgica, aunque la disfagia recurrente no ha disminuido con el tiempo. Las complicaciones menores relacionadas con el stent van en aumento, asociadas a la implementación de la quimiorradioterapia.

Identification of Polyphenols in Sea Fennel (Crithmum maritimum) and Seaside Arrowgrass (Triglochin maritima) Extracts with Antioxidant, ACE-I, DPP-IV and PEP-Inhibitory Capacity.

Sea fennel and seaside arrowgrass are two abundant but underutilized halophytes along the Atlantic and Mediterranean coasts. This study investigated the antioxidant capacity and the potential antihypertensive (Angiotensin Converting Enzyme I, ACE-I inhibition), hypoglycaemic (Dipeptidyl Peptidase IV, DPP-IV inhibition), and nootropic (Prolyl Endopeptidase, PEP inhibition) activity of their polyphenol extracts. They had a high phenol content (21-24 mEq GA/g), antioxidant capacity evaluated using the ABTS (17-2 mg ascorbic acid/g) and FRAP (170-270 mM Mohr's salt/g) assays, and effective ACE-inhibiting properties (80-90% inhibiting activity at final concentration of 0.5 mg/mL). Additionally, the sea fennel extract displayed high DPP-IV inhibitory capacity (73% at 1 mg/mL), while the seaside arrowgrass extract exhibited potent Prolyl endopeptidase inhibitory capacity (75% at 1 mg/mL). Fractionation by HPLC concentrated the bioactive molecules in two fractions, for which the composition was analyzed by LC-MS/MS. Different chlorogenic acids seemed to play an important role in the bioactivity of sea fennel extract, and different flavonoids, mainly apigenin, luteolin and chrysoeriol, in the bioactivity of the seaside arrowgrass extract. Given their potential health benefits, these extracts could serve as valuable bioactive ingredients and could potentially encourage the cultivation of these species in regions where traditional crops face challenges in growth.

In Vitro Comparison of Internal and Marginal Adaptation between Printed and Milled Onlays.

STATEMENT OF PROBLEM: Nowadays, milling is still the gold standard for fabricating indirect restorations, but to overcome its disadvantages, there are alternatives, such as 3D printing. PURPOSE: This study aimed to compare the gaps between the prepared tooth and milled and printed onlays fabricated with the same CAD design. It also aimed to determine the gap reproducibility across onlays fabricated by 3D printing and milling. METHODS: A resin tooth was prepared for an onlay. After scanning the preparation, an onlay was designed with proprietary dental software. Next, 22 onlays were milled in a graphene-reinforced PMMA disc (Group 1), and 22 onlays were 3D-printed with a hybrid composite material (Group 2). After that, all fabricated restorations were scanned and superimposed on the scanned prepared resin tooth. Subsequently, a specific software was used to measure the margin, central, and intaglio-located gap between the milled or printed restoration and the preparation. Finally, measurements were compared with a multifactor analysis of variance. RESULTS: The results demonstrated that printed onlays (Group 2) adapted better to the prepared tooth than the milled ones (Group 1) (p < 0.05). The comparison of standard deviations showed the better gap reproducibility of printed onlays (p < 0.05). CONCLUSION: This study concluded that the printed onlays adapted significantly better to the prepared tooth than the milled onlays. Printed onlays also showed significantly better gap reproducibility.

[Morbidity due to chronic diseases and their health care in Asturias: a gender analysis]. / Morbilidad por enfermedades crónicas y su atención sanitaria en Asturias: análisis de género.

OBJECTIVE: To determine gender differences in the magnitude and complexity of chronic diseases and gender inequalities in health care in the adult population of Asturias in 2022. METHOD: A cross-sectional population study in people (>14 years) with at least one diagnosis of chronic disease (780,566 inhabitants). SOURCES OF INFORMATION: computer program for morbidity groups (Ministry of Health), Electronic medical record of primary care and hospital. Comparative analysis by sex and age, the mean values of chronic diseases and complexity index (Student's t test and one-way ANOVA), and probability (odds ratio and 95% CI) of suffering from specific chronic diseases, making one or more visits to the hospital emergency department or one or more admissions to hospital. RESULTS: 89.9% of women and 82.1% of men were registered with at least one chronic disease. The mean was higher in women (4.36) than in men (3.22) (p<0.001). Complexity index: men 4.56 and women 5.85 (p<0.001). Results show that women are more likely to attend the hospital emergency department, with an attendance rate of 50% for the diseases cited, compared with men at 29%. The rate of hospital admission is higher in men in 13 of the 14 diseases studied (85%). CONCLUSIONS: Gender analysis can also be applied to secondary sources of the National Health System. Despite the greater magnitude and complexity of chronic diseases in women, there is a higher frequency of hospital admissions in men compared to women with the same diseases. This implies an unequal care profile in the field of hospital admissions that the scientific literature associates with gender biases in health care.

Evaluation of by-products from agricultural, livestock and fishing industries as nutrient source for the production of proteolytic enzymes.

This study presents an approach that utilizes low-value agro-industrial by-products as culture media for producing high-value proteolytic enzymes. The objective was to assess the impact of six agro-industrial by-products as culture media on the production of proteolytic enzymes. Bacillus subtilis strains, confirmed through comprehensive biochemical, morphological, and molecular analyses, were isolated and identified. Enzymatic activity was evaluated using azocasein and casein substrates, and the molecular sizes of the purified extract components were determined. The results demonstrated that the isolated bacteria exhibited higher metabolic and enzymatic activity when cultured in media containing 1 % soybean oil cake or feather meal. Furthermore, higher concentrations of the culture media were found to hinder the production of protease. Optimal protease synthesis on soybean oil cake and feather meal media was achieved after 4 days, using both the azocasein and casein methods. Semi-purification of the enzymatic extract obtained from Bacillus subtilis in feather meal and soybean oil cake resulted in a significant increase in azocaseinolytic and caseinolytic activities. Gel electrophoresis analysis revealed multiple bands in the fractions with the highest enzymatic activity in soybean oil cake, indicating the presence of various enzymes with varying molecular sizes. These findings highlight the potential of utilizing low-value agro-industrial by-products as efficient culture media for the sustainable and economically viable production of proteolytic enzymes with promising applications in various industries.

A numerical simulation study of the hydrodynamic effects caused by morphological changes in the Guadalquivir River Estuary.

This study presents an analysis of the impacts of the changes in bottom depth along the Guadalquivir Estuary on tidal dynamics. A realistic non-linear 1D numerical model, incorporating changes in both breadth and bottom depth, was employed to investigate the involved effects. The findings reveal a significant amplification of the M2 tidal wave towards the upper region of the Estuary, resulting from the gradual deepening caused by multiple dredging operations. The Estuary exhibits a pronounced tendency towards resonance, which is further enhanced by its deepening, resulting in reduced bottom friction and a smaller decrease in tidal wave amplitude as it propagates through the Estuary. The alterations in depth, particularly in breadth, along the Estuary play a crucial role in determining the magnitude of the resonant response of the M2 tidal wave.

A precisely humanized FCRN transgenic mouse for preclinical pharmacokinetics studies.

Monoclonal antibodies (mAbs) are one of the fastest-growing classes of drugs and have been approved to treat several diseases, including cancers and autoimmune disorders. Preclinical pharmacokinetics studies are performed to determine the therapeutically meaningful dosages and efficacy of candidate drugs. These studies are typically performed in non-human primates; however, using primates is costly and raises ethical considerations. As a result, rodent models that better mimic human-like pharmacokinetics have been generated and remain an area of active investigation. Pharmacokinetic characteristics of a candidate drug, such as half-life, are partly controlled by antibody binding to the human neonatal receptor hFCRN. Due to the abnormally high binding of human antibodies to mouse FCRN, traditional laboratory rodents do not accurately model the pharmacokinetics of human mAbs. In response, humanized rodents expressing hFCRN have been generated. However, these models generally use large inserts randomly integrated into the mouse genome. Here, we report the production and characterization of a CRISPR/Cas9-mediated hFCRN transgenic mouse termed SYNB-hFCRN. Using CRISPR/Cas9-assisted gene targeting, we prepared a strain with a simultaneous knockout of mFcrn and insertion of a hFCRN mini-gene under the control of the endogenous mouse promoter. These mice are healthy and express hFCRN in the appropriate tissues and immune cell subtypes. Pharmacokinetic evaluation of human IgG and adalimumab (Humira®) demonstrate hFCRN-mediated protection. These newly generated SYNB-hFCRN mice provide another valuable animal model for use in preclinical pharmacokinetics studies during early drug development.

Identification of ACE I-Inhibitory Peptides Released by the Hydrolysis of Tub Gurnard (Chelidonichthys lucerna) Skin Proteins and the Impact of Their In Silico Gastrointestinal Digestion.

Tub gurnard is a highly abundant fishery species caught as a discard in the Mediterranean Sea. This work proposes its valorisation through the release of potential antihypertensive peptides and glycosaminoglycans (GAGs) through the controlled hydrolysis of tub gurnard skin proteins. Four proteases (Esperase, Alcalase, Trypsin and Pronase E) were used to obtain potent angiotensin converting enzyme I (ACE)-inhibitory hydrolysates. Peptides and GAGs were separated and evaluated for their antihypertensive potential by fluorometry. The peptide-rich fractions derived from the Esperase and Alcalase hydrolysates showed very low IC50 values (47 and 68 µg/mL, respectively). Only the GAGs from the Trypsin and Esperase hydrolysates were relevant ACE inhibitors (63 and 52% at 1 mg/mL, respectively). The peptide composition of the most potent ACE-inhibitory fractions derived from the Esperase and Alcalase hydrolysates (IC50 values of 33 and 29 µg/mL, respectively) was analysed by RP-LC-ESI-MS/MS. The analysis suggests that the ACE-inhibitory activity is related to the peptide hydrophobicity, as well as to the presence of specific residues at any of the last four C-terminal positions. The in silico gastrointestinal digestion of these fractions yielded small peptides with antihypertensive potential.

Single-dose psilocybin for a treatment-resistant episode of major depression: Impact on patient-reported depression severity, anxiety, function, and quality of life.

BACKGROUND: COMP360 is a proprietary, synthetic formulation of psilocybin being developed for treatment-resistant depression (TRD), a burdensome, life-threatening illness with high global impact. Here, we expand upon the previous report of primary outcomes from a phase 2 study of COMP360 in individuals with TRD-the largest randomised controlled clinical trial of psilocybin-to discuss findings of the exploratory efficacy endpoints. METHODS: In this phase 2, double-blind trial, 233 participants with TRD were randomised to receive a single dose of psilocybin 25 mg, 10 mg, or 1 mg (control), administered alongside psychological support from trained therapists. Efficacy measures assessed patient-reported depression severity, anxiety, positive and negative affect, functioning and associated disability, quality of life, and cognitive function. RESULTS: At Week 3, psilocybin 25 mg, compared with 1 mg, was associated with greater improvements from Baseline total scores in all measures. The 10 mg dose produced smaller effects across these measures. LIMITATIONS: Interpretation of this trial is limited by the absence of an active comparator and the possibility of functional unblinding in participants who received a low dose of psilocybin. CONCLUSIONS: Three weeks after dosing, psilocybin 25 mg and, to a lesser degree, 10 mg improved measures of patient-reported depression severity, anxiety, affect, and functioning. These results extend the primary findings from the largest randomised clinical trial of psilocybin for TRD to examine other outcomes that are of importance to patients.

High-resolution characterization of intertidal areas and lowest astronomical tidal surface by use of Sentinel-2 multispectral imagery and hydrodynamic modeling: Case-study in Cadiz Bay (Spain).

In intertidal areas, the zonation is determined by factors such as sea-level and topography. For this reason, a mixed methodology for the characterization (topography, extension, and zonation) of maximum intertidal areas is presented, based upon multispectral satellite imagery, hydrodynamic modeling, and in situ measurements. The methodology is applied and validated in the inner Cadiz Bay (SW Spain) as a case study. Satellite-derived waterlines were vertically referenced by tide-gauge measurements of sea-level; the resulting partial topography of intertidal areas was integrated into available hydrographic/topographic data to elaborate a high-resolution (10 m) model grid from which hydrodynamic simulations were conducted. Model results for lowest and highest tidal level situations were used to characterize the maximum intertidal areas within the inner Cadiz Bay, as well as the lowest astronomical tidal surface (LAT). The obtained LAT, referenced with respect the chosen geoid and/or ellipsoid, was identified with the vertical reference surface for Hydrography (VRSH) in this environment, complementing and improving the official VRSH presently being developed for Spanish waters. Obtained results show errors of the order of 1 cm for sea-level amplitudes and <1 min for the main tidal lags when comparing with tide-gauge data. Further applications of this exportable, relatively fast, low-cost, and accurate methodology are outlined.

Morbilidad por enfermedades crónicas y su atención sanitaria en Asturias: análisis de género / Morbidity due to chronic diseases and their health care in Asturias: a gender analysis

Objetivo: Determinar las diferencias según sexo de la magnitud y la complejidad por enfermedades crónicas, y las desigualdades de género, en la atención sanitaria de la población adulta en Asturias en el año 2022. Método: Estudio transversal poblacional en mayores de 14 años con al menos un diagnóstico de enfermedad crónica (780.566 habitantes). Fuentes de información: programa informático de grupos de morbilidad (Ministerio de Sanidad), Historia clínica electrónica de atención primaria y hospitalaria. Análisis comparativo por sexo y edad: medias de patologías crónicas e índice de complejidad (t de Student y ANOVA de un factor), y probabilidad (odds ratio e intervalo de confianza del 95%) de padecer enfermedades crónicas específicas, realizar una o más visitas a urgencias, e ingresos hospitalarios. Resultados: En atención primaria se registraron un 89,9% de mujeres y un 82,1% de hombres con al menos una enfermedad crónica. La media fue mayor en las mujeres (4,36) que en los hombres (3,22) (p < 0,001). Índice de complejidad: hombres 4,56 y mujeres 5,85 (p < 0,001). Mientras que la probabilidad de acudir a urgencias es superior en las mujeres en el 50% de las patologías (hombres 29%), la probabilidad de ingresar es superior en los hombres en 13 de las 14 patologías estudiadas (85%). Conclusiones: El análisis de género también se puede aplicar en fuentes secundarias del Sistema Nacional de Salud. Pese a la mayor magnitud y complejidad en las mujeres, la mayor frecuencia de hospitalizaciones en los hombres que en las mujeres con las mismas patologías supone un perfil de atención desigual en el ámbito de ingresos hospitalarios que la literatura científica relaciona con sesgos de género en la atención sanitaria.(AU)

Objective: To determine gender differences in the magnitude and complexity of chronic diseases and gender inequalities in health care in the adult population of Asturias in 2022. Method: A cross-sectional population study in people (>14 years) with at least one diagnosis of chronic disease (780,566 inhabitants). Sources of information: computer program for morbidity groups (Ministry of Health), Electronic medical record of primary care and hospital. Comparative analysis by sex and age, the mean values of chronic diseases and complexity index (Student's t test and one-way ANOVA), and probability (odds ratio and 95% CI) of suffering from specific chronic diseases, making one or more visits to the hospital emergency department or one or more admissions to hospital. Results: 89.9% of women and 82.1% of men were registered with at least one chronic disease. The mean was higher in women (4.36) than in men (3.22) (p < 0.001). Complexity index: men 4.56 and women 5.85 (p < 0.001). Results show that women are more likely to attend the hospital emergency department, with an attendance rate of 50% for the diseases cited, compared with men at 29%. The rate of hospital admission is higher in men in 13 of the 14 diseases studied (85%). Conclusions: Gender analysis can also be applied to secondary sources of the National Health System. Despite the greater magnitude and complexity of chronic diseases in women, there is a higher frequency of hospital admissions in men compared to women with the same diseases. This implies an unequal care profile in the field of hospital admissions that the scientific literature associates with gender biases in health care.(AU)

Transient gestational hypothyroxinemia accelerates and enhances ulcerative colitis-like disorder in the male offspring.

Introduction: Gestational hypothyroxinemia (HTX) is a condition that occurs frequently at the beginning of pregnancy, and it correlates with cognitive impairment, autism, and attentional deficit in the offspring. Evidence in animal models suggests that gestational HTX can increase the susceptibility of the offspring to develop strong inflammation in immune-mediated inflammatory diseases. Ulcerative colitis (UC) is a frequent inflammatory bowel disease with unknown causes. Therefore, the intensity of ulcerative colitis-like disorder (UCLD) and the cellular and molecular factors involved in proinflammatory or anti-inflammatory responses were analyzed in the offspring gestated in HTX (HTX-offspring) and compared with the offspring gestated in euthyroidism (Control-offspring). Methods: Gestational HTX was induced by the administration of 2-mercapto-1-methylimidazole in drinking water to pregnant mice during E10-E14. The HTX-offspring were induced with UCLD by the acute administration of dextran sodium sulfate (DSS). The score of UCLD symptomatology was registered every day, and colon histopathology, immune cells, and molecular factors involved in the inflammatory or anti-inflammatory response were analyzed on day 6 of DSS treatment. Results: The HTX-offspring displayed earlier UCLD pathological symptoms compared with the Control-offspring. After 6 days of DSS treatment, the HTX-offspring almost doubled the score of the Control-offspring. The histopathological analyses of the colon samples showed signs of inflammation at the distal and medial colon for both the HTX-offspring and Control-offspring. However, significantly more inflammatory features were detected in the proximal colon of the HTX-offspring induced with UCLD compared with the Control-offspring induced with UCLD. Significantly reduced mRNA contents encoding for protective molecules like glutamate-cysteine ligase catalytic subunit (GCLC) and mucin-2 (MUC-2) were found in the colon of the HTX-offspring as compared with the Control-offspring. Higher percentages of Th17 lymphocytes were detected in the colon tissues of the HTX-offspring induced or not with UCLD as compared with the Control-offspring. Discussion: Gestational HTX accelerates the onset and increases the intensity of UCLD in the offspring. The low expression of MUC-2 and GCLC together with high levels of Th17 Lymphocytes in the colon tissue suggests that the HTX-offspring has molecular and cellular features that favor inflammation and tissue damage. These results are important evidence to be aware of the impact of gestational HTX as a risk factor for UCLD development in offspring.

Fabrication of a CAD-CAM combination matrix for trial restorations: A dental technique.

The trial restoration increases outcome predictability in restorative treatments, enhances communication among specialists and patients, and guides tooth preparations. It should reproduce the planned design precisely because many decisions will be made based on the transferred design. Traditionally, a diagnostic waxing design is transferred to the mouth with a flexible silicone matrix. However, a rigid matrix would ensure an accurate transfer of the planned design by avoiding the deformation of the silicone index. A step-by-step technique for fabricating a computer-aided design and computer-aided manufactured (CAD-CAM) rigid matrix relined with polyvinyl siloxane material to fabricate a trial restoration is presented. The technique ensures accurate detail reproduction and dimensional stability, avoiding deformation and ensuring a predictable transfer of the planned design.

Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression.

BACKGROUND: Psilocybin is being studied for use in treatment-resistant depression. METHODS: In this phase 2 double-blind trial, we randomly assigned adults with treatment-resistant depression to receive a single dose of a proprietary, synthetic formulation of psilocybin at a dose of 25 mg, 10 mg, or 1 mg (control), along with psychological support. The primary end point was the change from baseline to week 3 in the total score on the Montgomery-Åsberg Depression Rating Scale (MADRS; range, 0 to 60, with higher scores indicating more severe depression). Secondary end points included response at week 3 (≥50% decrease from baseline in the MADRS total score), remission at week 3 (MADRS total score ≤10), and sustained response at 12 weeks (meeting response criteria at week 3 and all subsequent visits). RESULTS: A total of 79 participants were in the 25-mg group, 75 in the 10-mg group, and 79 in the 1-mg group. The mean MADRS total score at baseline was 32 or 33 in each group. Least-squares mean changes from baseline to week 3 in the score were -12.0 for 25 mg, -7.9 for 10 mg, and -5.4 for 1 mg; the difference between the 25-mg group and 1-mg group was -6.6 (95% confidence interval [CI], -10.2 to -2.9; P<0.001) and between the 10-mg group and 1-mg group was -2.5 (95% CI, -6.2 to 1.2; P = 0.18). In the 25-mg group, the incidences of response and remission at 3 weeks, but not sustained response at 12 weeks, were generally supportive of the primary results. Adverse events occurred in 179 of 233 participants (77%) and included headache, nausea, and dizziness. Suicidal ideation or behavior or self-injury occurred in all dose groups. CONCLUSIONS: In this phase 2 trial involving participants with treatment-resistant depression, psilocybin at a single dose of 25 mg, but not 10 mg, reduced depression scores significantly more than a 1-mg dose over a period of 3 weeks but was associated with adverse effects. Larger and longer trials, including comparison with existing treatments, are required to determine the efficacy and safety of psilocybin for this disorder. (Funded by COMPASS Pathfinder; EudraCT number, 2017-003288-36; ClinicalTrials.gov number, NCT03775200.).

[Clinical, obstetric and perinatal characteristics of Mexican pregnant women with COVID-19]. / Características clínicas, obstétricas y perinatales de embarazadas mexicanas con Covid-19.

Background: COVID-19 disease is the leading cause of maternal death in Mexico. The data published to date indicate that pregnancy favors severe forms of the disease. Objective: To describe the clinical, obstetric and perinatal characteristics of pregnant women with COVID-19 disease treated at the UMAE "Luis Castelazo Ayala" of the Instituto Mexicano del Seguro Social. Material and methods: Observational, cross-sectional and retrospective study of pregnant women with COVID-19 treated from March to December 2020. The epidemiological characteristics, complications and perinatal results were analyzed with descriptive and inferential statistics. Results: 133 patients included: 84.5% with mild disease, 8 % moderate and 8.5% severe and critical. Pre-existing comorbidities: obesity, diabetes and hypothyroidism. Main symptoms: cough, headache, fever, rhinorrhea and anosmia. In severe and critical cases, tachycardia, tachypnea, and hypoxemia were present. Lymphoneutropenia, hyperglycemia, and transaminasemia were seen in severe and critical forms. Fibrinogen and D dimer stayed unchanged. Preterm delivery, oligohydramnios, gestational hypertension, severe preeclampsia, and pneumonia were the main complications. 75% of the newborns without complications. Conclusions: The clinical behavior of the disease was mostly mild and even in moderate cases, and even in moderate as well as severe and complicated cases, the binomial results were favorable. There was no maternal death.

Introducción: la enfermedad COVID-19 en el embarazo es la primera causa de muerte materna en México, y se ha reportado que favorece las formas graves de la enfermedad. Objetivo: describir las características clínicas, obstétricas y perinatales de pacientes embarazadas con enfermedad COVID-19 atendidas en la UMAE "Luis Castelazo Ayala" del Instituto Mexicano del Seguro Social (IMSS). Material y métodos: estudio observacional, transversal y retrospectivo de pacientes embarazadas con COVID-19 atendidas de marzo a diciembre del 2020. Las características epidemiológicas, complicaciones y resultados perinatales se analizaron con estadística descriptiva e inferencial. Resultados: se incluyeron 133 pacientes: 84.5% presentaron enfermedad leve, 8% moderada y 8.5% severa y crítica. Las comorbilidades preexistentes fueron: obesidad, diabetes e hipotiroidismo. Los principales síntomas: tos, cefalea, fiebre, rinorrea y anosmia. En casos severos y críticos la taquicardia, taquipnea e hipoxemia estuvieron presentes. En las formas severa y crítica se observaron: linfoneutropenia, hiperglucemia y transaminasemia. El fibrinógeno y dímero D sin cambios. El parto pretérmino, el oligohidroamnios, la hipertensión gestacional, la preeclampsia severa y la neumonia fueron las principales complicaciones. El 75% de los recién nacidos no preentaron complicaciones. Conclusiones: el comportamiento clínico de la enfermedad fue, en su mayoría, leve, e incluso en los casos moderados así como en los severos y complicados los resultados del binomio fueron favorables. No hubo muerte materna ni se evidenció transmisión vertical.

Antioxidant, Antihypertensive, Hypoglycaemic and Nootropic Activity of a Polyphenolic Extract from the Halophyte Ice Plant (Mesembryanthemum crystallinum).

This study aims to determine the potential antioxidant, antihypertensive, hypoglycaemic and nootropic activity of a purified polyphenolic extract from the halophyte ice plant (Mesembryanthemum crystallinum). The ice plant extract showed good antioxidant activity measured by DPPH, ORAC, TEAC, FRAP and ferrous ion chelating activity. Moreover, the extract showed potent ACE, DPP-IV and PEP-inhibitory activity (90.5%, 98.6% and 73.1%, respectively, at a final concentration of 1 mg/mL). The extract was fractionated and the fraction with the highest content of total phenolic compounds showed the highest bioactivity, suggesting that polyphenols could be mainly responsible for the abovementioned activities. The tentative polyphenol identification by HPLC-ESI-QTOF-MS in this fraction revealed that flavones (>65%) are the major group, with apigenin (38%) predominating, followed by diosmin (17.7%) and luteolin (11.9%). They could presumably be the main elements responsible for the enzymatic inhibition activity. Additionally, 4-hydroxybenzoic acid, p-coumaric acid and a hydroxycinnamic acid derivative (2-O-(p-cumaroyl)-l-malic acid) were found in the extract. To our knowledge, this is the first time that some of these activities have been reported for halophyte extracts.