Testing behaviour change with an artificial intelligence chatbot in a randomized controlled study.

Chatbots can effect large-scale behaviour change because they are accessible through social media, flexible, scalable, and gather data automatically. Yet research on the feasibility and effectiveness of chatbot-administered behaviour change interventions is sparse. The effectiveness of established behaviour change interventions when implemented in chatbots is not guaranteed, given the unique human-machine interaction dynamics. We pilot-tested chatbot-based behaviour change through information provision and embedded animations. We evaluated whether the chatbot could increase understanding and intentions to adopt protective behaviours during the pandemic. Fifty-nine culturally and linguistically diverse participants received a compassion intervention, an exponential growth intervention, or no intervention. We measured participants' COVID-19 testing intentions and measured their staying-home attitudes before and after their chatbot interaction. We found reduced uncertainty about protective behaviours. The exponential growth intervention increased participants' testing intentions. This study provides preliminary evidence that chatbots can spark behaviour change, with applications in diverse and underrepresented groups.

Comparative analysis of leukemia and risk estimation in working age population between provinces of Ecuador.

Leukemia is associated with exposure to radiation, benzene derivatives, and pesticides. Previous research has documented an increase in work-related leukemia in the Latin American Andean region. To date, there are only few studies in Ecuador on the impact of oil exploitation on adjacent indigenous communities. Our study aims to show the impact of leukemia on the working-age population. For the calculation of morbidity and mortality rates, we used hospital discharge and death records from the National Institute of Statistics of Ecuador. These data were collected and adjusted to the corresponding province's population for further analysis. Large differences were observed between provinces in adjusted rates of leukemia mortality and morbidity in the working-age population. The variations in altitude among different areas in Ecuador give the provinces a distinct geographic identity. Likewise, the provinces with the highest morbidity and mortality rankings, such as Azuay, Loja, Imbabura, and Tungurahua, have an average altitude above 2000 meters. As a result, there are variations in the average temperature, exposure to solar and cosmic radiation, and mining and farming methods. The observed differences warrant the future collection of geolocation data for affected individuals. This could help to better understand how leukemia cases have demogrpahic hotspots in the country, identify possible risk factors associated with the disease in each region, and design more effective prevention and control strategies.

La leucemia es una enfermedad a consecuencia, además de factores genéticos, de la exposición a radiaciones, derivados del benceno y pesticidas. Investigaciones anteriores han documentado un aumento de la leucemia ocupacional en la región andina de América Latina. Hasta la fecha, existen sólo unos pocos estudios en Ecuador sobre el impacto de la explotación petrolera en las comunidades indígenas. Nuestro objetivo es mostrar el impacto de la leucemia en la población en edad de trabajar. Para el cálculo de las tasas de morbimortalidad se utilizaron los registros de altas hospitalarias y defunciones del Instituto Nacional de Estadística del Ecuador. Estos datos fueron recopilados y estimadas las tasas ajustadas. Se observaron grandes diferencias entre provincias en las tasas ajustadas de mortalidad y morbilidad por leucemia en la población en edad de trabajar. Asimismo, las provincias con mayor ranking de morbilidad y mortalidad, como Azuay, Loja, Imbabura y Tungurahua, coinciden en tener una altitud promedio superior a los 2000 metros. Hay provincias de baja altitud en la costa y provincias por encima de los 2000 metros en la sierra, lo que le da a las provincias del Ecuador una identidad geográfica distintiva. Como resultado, existen variaciones en la temperatura promedio, la exposición a la radiación solar y cósmica, y actividades de minería y agricultura. Las diferencias observadas, recomiendan la recopilación futura de datos de geolocalización de las personas afectadas. Esto podría ayudarnos a comprender mejor cómo se distribuyen los casos de leucemia, identificar posibles factores de riesgo asociados a la enfermedad en cada región y diseñar estrategias de prevención y control más efectivas.

An artificial intelligence-assisted system versus white light endoscopy alone for adenoma detection in individuals with Lynch syndrome (TIMELY): an international, multicentre, randomised controlled trial.

BACKGROUND: Computer-aided detection (CADe) systems for colonoscopy have been shown to increase small polyp detection during colonoscopy in the general population. People with Lynch syndrome represent an ideal target population for CADe-assisted colonoscopy because adenomas, the primary cancer precursor lesions, are characterised by their small size and higher likelihood of showing advanced histology. We aimed to evaluate the performance of CADe-assisted colonoscopy in detecting adenomas in individuals with Lynch syndrome. METHODS: TIMELY was an international, multicentre, parallel, randomised controlled trial done in 11 academic centres and six community centres in Belgium, Germany, Italy, and Spain. We enrolled individuals aged 18 years or older with pathogenic or likely pathogenic MLH1, MSH2, MSH6, or EPCAM variants. Participants were consecutively randomly assigned (1:1) to either CADe (GI Genius) assisted white light endoscopy (WLE) or WLE alone. A centre-stratified randomisation sequence was generated through a computer-generated system with a separate randomisation list for each centre according to block-permuted randomisation (block size 26 patients per centre). Allocation was automatically provided by the online AEG-REDCap database. Participants were masked to the random assignment but endoscopists were not. The primary outcome was the mean number of adenomas per colonoscopy, calculated by dividing the total number of adenomas detected by the total number of colonoscopies and assessed in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04909671. FINDINGS: Between Sept 13, 2021, and April 6, 2023, 456 participants were screened for eligibility, 430 of whom were randomly assigned to receive CADe-assisted colonoscopy (n=214) or WLE (n=216). 256 (60%) participants were female and 174 (40%) were male. In the intention-to-treat analysis, the mean number of adenomas per colonoscopy was 0·64 (SD 1·57) in the CADe group and 0·64 (1·17) in the WLE group (adjusted rate ratio 1·03 [95% CI 0·72-1·47); p=0·87). No adverse events were reported during the trial. INTERPRETATION: In this multicentre international trial, CADe did not improve the detection of adenomas in individuals with Lynch syndrome. High-quality procedures and thorough inspection and exposure of the colonic mucosa remain the cornerstone in surveillance of Lynch syndrome. FUNDING: Spanish Gastroenterology Association, Spanish Society of Digestive Endoscopy, European Society of Gastrointestinal Endoscopy, Societat Catalana de Digestologia, Instituto Carlos III, Beca de la Marato de TV3 2020. Co-funded by the European Union.

Development and validation of a faecal immunochemical test-based model in the work-up of patients with iron deficiency anaemia.

Objective: In patients with iron deficiency anaemia (IDA), the diagnostic yield of gastroscopy and colonoscopy (bidirectional endoscopy) in detecting neoplastic lesions is low. This study aimed to develop and validate a faecal immunochemical test (FIT)-based model to optimise the work-up of patients with IDA. Methods: Outpatients with IDA were enrolled in a prospective, multicentre study from April 2016 to October 2019. One FIT was performed before bidirectional endoscopy. Significant gastrointestinal lesions were recorded and a combined model developed with variables that were independently associated with significant colorectal lesions in the multivariate analysis. The model cut-off was selected to provide a sensitivity of at least 95% for colorectal cancer (CRC) detection, and its performance was compared to different FIT cut-offs. The data set was randomly split into two groups (developed and validation cohorts). An online calculator was developed for clinical application. Results: The development and validation cohorts included 373 and 160 patients, respectively. The developed model included FIT value, age, and sex. In the development and validation cohorts, a model cut-off of 0.1375 provided a negative predictive value of 98.1 and 96.7% for CRC and 90.7 and 88.3% for significant colorectal lesions, respectively. This combined model reduced the rate of missed significant colorectal lesions compared to FIT alone and could have avoided more than one-fourth of colonoscopies. Conclusion: The FIT-based combined model developed in this study may serve as a useful diagnostic tool to triage IDA patients for early endoscopic referral, resulting in considerable reduction of unnecessary colonoscopies.

Targeting calciumopathy for neuroprotection: focus on calcium channels Cav1, Orai1 and P2X7.

As the uncontrolled entry of calcium ions (Ca2+) through plasmalemmal calcium channels is a cell death trigger, the conjecture is here raised that mitigating such an excess of Ca2+ entry should rescue from death the vulnerable neurons in neurodegenerative diseases (NDDs). However, this supposition has failed in some clinical trials (CTs). Thus, a recent CT tested whether isradipine, a blocker of the Cav1 subtype of voltage-operated calcium channels (VOCCs), exerted a benefit in patients with Parkinson's disease (PD); however, outcomes were negative. This is one more of the hundreds of CTs done under the principle of one-drug-one-target, that have failed in Alzheimer's disease (AD) and other NDDs during the last three decades. As there are myriad calcium channels to let Ca2+ ions gain the cell cytosol, it seems reasonable to predict that blockade of Ca2+ entry through a single channel may not be capable of preventing the Ca2+ flood of cells by the uncontrolled Ca2+ entry. Furthermore, as Ca2+ signaling is involved in the regulation of myriad functions in different cell types, it seems also reasonable to guess that a therapy should be more efficient by targeting different cells with various drugs. Here, we propose to mitigate Ca2+ entry by the simultaneous partial blockade of three quite different subtypes of plasmalemmal calcium channels that is, the Cav1 subtype of VOCCs, the Orai1 store-operated calcium channel (SOCC), and the purinergic P2X7 calcium channel. All three channels are expressed in both microglia and neurons. Thus, by targeting the three channels with a combination of three drug blockers we expect favorable changes in some of the pathogenic features of NDDs, namely (i) to mitigate Ca2+ entry into microglia; (ii) to decrease the Ca2+-dependent microglia activation; (iii) to decrease the sustained neuroinflammation; (iv) to decrease the uncontrolled Ca2+ entry into neurons; (v) to rescue vulnerable neurons from death; and (vi) to delay disease progression. In this review we discuss the arguments underlying our triad hypothesis in the sense that the combination of three repositioned medicines targeting Cav1, Orai1, and P2X7 calcium channels could boost neuroprotection and delay the progression of AD and other NDDs.

Ecuadorian Provinces with High Morbidity and Mortality Rates Due to Asthma among the Working-Age Population: An Ecological Study to Promote Respiratory Health.

Asthma is a significant public health concern. This study identified the provinces with the highest morbidity and mortality rates due to asthma among the working-age population (15-69 years) in the Republic of Ecuador. The secondary objective was to explain the possible differences attributable to occupational exposure. This nationwide ecological study was conducted in 24 provinces between 2016 and 2019. Government databases were used as sources of information. Age-standardized rates were calculated for codes J45 and J46. The hospitalization morbidity rate for asthma decreased from 6.51 to 5.76 cases per 100,000 working-age population, and the mortality rate has consistently been low and stable from 0.14 to 0.15 deaths per 100,000 working-age population. Geographic differences between the provinces were evident. The risk of hospitalization and death due to asthma was higher in the Pacific coast (Manabí with 7.26 and 0.38, Esmeraldas with 6.24 and 0.43, Los Ríos with 4.16 and 0.40, El Oro with 7.98 and 0.21, Guayas with 4.42 and 0.17 and the Andean region (Azuay with 6.33 and 0.45, Cotopaxi (5.84 and 0.48)). The high rates observed in provinces with greater agricultural and industrial development could be national heterogeneity's main determinants and act as occupational risk factors. The contribution of occupational hazards in each province should be examined in depth through ad hoc studies. The findings presented here provide valuable information that should prompt further detailed studies, which will assist in designing public policies aimed at promoting and safeguarding the respiratory health of the population, particularly that of workers. We believe that this study will inspire the creation of regional networks for the research and surveillance of occupational health.

Comparison of baseline clinical characteristics among people with type 2 diabetes on second-line therapy previously added with dapagliflozin or another oral glucose-lowering drug: AGORA study.

INTRODUCTION: Type 2 diabetes mellitus (T2D) has acquired epidemic proportions worldwide. In recent years, new oral glucose-lowering drugs (OGLD) have emerged that improve the cardiovascular-kidney-metabolic control in T2D people. OBJECTIVES: To compare the baseline clinical-biological characteristics among T2D people to whom had added-on dapagliflozin (DAPA group) or another OGLD (SOC group) second-line hypoglycaemic therapies among the AGORA study population. METHODS: This is a multicentre cross-sectional observational study of the baseline characteristics of T2D people recruited through competitive sampling among 46 primary care health centres in Spain for the AGORA study. The inclusion and exclusion criteria of participants, and justification of the sample size are reported. After verifying the data necessary to be evaluated and informed consent, 317 subjects were included to the DAPA group and 288 to the SOC group. Both categorical and continuous variables were analysed and compared with the usual statistics. Cohen's d was used to assess the standardised difference in means. RESULTS: Six hundred and five patients with T2D were assessed (mean age 63.5 [SD±8.1] years, 61.8% men), whom 17.4% were smokers, 47.6% had obesity, 74.8% hypertension, 87.3% dyslipidaemia, and 41.7% reported physical inactivity, with no significant differences between both comparison groups. The mean (SD) evolution time of T2D was 10.1 (5.6) years. Most baseline clinical-biological characteristics at recruitment were similar in both groups. However, DAPA group was younger (2.9 years), and had lower systolic blood pressure (SBP) (2.8mmHg), higher body weight (BW) (3.7kg), and higher glycated haemoglobin A1c (HbA1c) (0.3%) than SOC group. Only 11.5% of participants had poor glycaemic control (HbA1c>8%) at recruitment, 54.9% had good glycaemic control (HbA1c<7%), being significantly lower in the DAPA group (47.3%) than in the SOC group (63.4%). The percentage of T2D patients with high vascular risk (VR) was 46.3%, and 53.7% with very high VR, being significantly higher in the DAPA group (57.4%) than in the SOC group (49.6%). CONCLUSIONS: Most baseline cardiovascular-kidney-metabolic characteristics were similar in T2D patients whom had added dapagliflozin on second-line hypoglycaemic therapy as those whom had added-on another OGLD. However, patients whom had added-on dapagliflozin had higher VR, lower SBP, higher BW, and slightly worse HbA1c control. Future research is necessary to explain the causes of these differences in cardiometabolic control.

Preliminary Investigation of Astragalus arpilobus subsp. hauarensis: LC-MS/MS Chemical Profiling, In Vitro Evaluation of Antioxidant, Anti-Inflammatory Properties, Cytotoxicity, and In Silico Analysis against COX-2.

The search results offer comprehensive insights into the phenolic compounds, antioxidant, anti-inflammatory, cytotoxic effects, LC-MS/MS analysis, molecular docking, and MD simulation of the identified phenolic compounds in the Astragalus arpilobus subsp. hauarensis extract (AAH). The analysis revealed substantial levels of total phenolic content (TPC), with a measured value of 191 ± 0.03 mg GAE/g DM. This high TPC was primarily attributed to two key phenolic compounds: total flavonoid content (TFC) and total tannin content (TTC), quantified at 80.82 ± 0.02 mg QE/g DM and 51.91 ± 0.01 mg CE/g DM, respectively. LC-MS/MS analysis identified 28 phenolic compounds, with gallic acid, protocatechuic acid, catechin, and others. In the DPPH scavenging assay, the IC50 value for the extract was determined to be 19.44 ± 0.04 µg/mL, comparable to standard antioxidants like BHA, BHT, ascorbic acid, and α-tocopherol. Regarding anti-inflammatory activity, the extract demonstrated a notably lower IC50 value compared to both diclofenac and ketoprofen, with values of 35.73 µg/mL, 63.78 µg/mL, and 164.79 µg/mL, respectively. Cytotoxicity analysis revealed significant cytotoxicity of the A. arpilobus extract, with an LC50 value of 28.84 µg/mL, which exceeded that of potassium dichromate (15.73 µg/mL), indicating its potential as a safer alternative for various applications. Molecular docking studies have highlighted chrysin as a promising COX-2 inhibitor, with favorable binding energies and interactions. Molecular dynamic simulations further support chrysin's potential, showing stable interactions with COX-2, comparable to the reference ligand S58. Overall, the study underscores the pharmacological potential of A. arpilobus extract, particularly chrysin, as a source of bioactive compounds with antioxidant and anti-inflammatory properties. Further research is warranted to elucidate the therapeutic mechanisms and clinical implications of these natural compounds.

Into the unknown: The role of post-fire soil erosion in the carbon cycle.

Wildfires directly emit 2.1 Pg carbon (C) to the atmosphere annually. The net effect of wildfires on the C cycle, however, involves many interacting source and sink processes beyond these emissions from combustion. Among those, the role of post-fire enhanced soil organic carbon (SOC) erosion as a C sink mechanism remains essentially unquantified. Wildfires can greatly enhance soil erosion due to the loss of protective vegetation cover and changes to soil structure and wettability. Post-fire SOC erosion acts as a C sink when off-site burial and stabilization of C eroded after a fire, together with the on-site recovery of SOC content, exceed the C losses during its post-fire transport. Here we synthesize published data on post-fire SOC erosion and evaluate its overall potential to act as longer-term C sink. To explore its quantitative importance, we also model its magnitude at continental scale using the 2017 wildfire season in Europe. Our estimations show that the C sink ability of SOC water erosion during the first post-fire year could account for around 13% of the C emissions produced by wildland fires. This indicates that post-fire SOC erosion is a quantitatively important process in the overall C balance of fires and highlights the need for more field data to further validate this initial assessment.

One-Step Synthesis, Crystallography, and Acute Toxicity of Two Boron-Carbohydrate Adducts That Induce Sedation in Mice.

Boronic acids form diester bonds with cis-hydroxyl groups in carbohydrates. The formation of these adducts could impair the physical and chemical properties of precursors, even their biological activity. Two carbohydrate derivatives from d-fructose and d-arabinose and phenylboronic acid were synthesized in a straightforward one-step procedure and chemically characterized via spectroscopy and X-ray diffraction crystallography. Additionally, an acute toxicity test was performed to determine their lethal dose 50 (LD50) values by using Lorke's method. Analytical chemistry assays confirmed the formation of adducts by the generation of diester bonds with the ß-d-pyranose of carbohydrates, including signals corresponding to the formation of new bonds, such as the stretching of B-O bonds. NMR spectra yielded information about the stereoselectivity in the synthesis reaction: Just one signal was found in the range for the anomeric carbon in the 13C NMR spectra of both adducts. The acute toxicity tests showed that the LD50 value for both compounds was 1265 mg/kg, while the effective dose 50 (ED50) for sedation was 531 mg/kg. However, differences were found in the onset and lapse of sedation. For example, the arabinose derivative induced sedation for more than 48 h at 600 mg/kg, while the fructose derivative induced sedation for less than 6 h at the same dose without the death of the mice. Thus, we report for the first time two boron-containing carbohydrate derivatives inducing sedation after intraperitoneal administration. They are bioactive and highly safe agents. Further biological evaluation is desirable to explore their medical applications.

Health-Related Quality of Life Long-Term Study in Lung Transplant Patients: A Single-Center Experience.

INTRODUCTION: Health-related quality of life (HRQL) assessment plays a crucial role in the follow-up care of lung transplanted (LTx) patients. Previous reports have indicated that the HRQL achieved by these patients is often poorer compared to that of healthy individuals. However, the factors contributing to this lower HRQL remain unclear. This prospective study aimed to assess the effectiveness of using both a generic and a disease-specific HRQL instrument in evaluating the outcomes of patients who have undergone LTx. METHODS: A total of 111 LTx patients were enrolled in the study, with 88 survivors completing the 5-year follow-up and 23 nonsurvivors identified within the first 3 y. Among the participants, 84 underwent double LTx, while 27 received a single LTx. Patients were interviewed before LTx, at 6 mo post-transplantation, and annually thereafter. Two validated instruments were utilized: the Euro quality of life five dimensions, a generic measure, and the St. George's Respiratory Questionnaire (SGRQ), a disease-specific questionnaire. RESULTS: The study showed significant improvements in Euro Quality of Life five Dimensions scores from 6 mo after LTx. Specifically, the percentage of patients without Mobility problems increased from 23% before LTx to 71% at 5 y (P = <0.001), while the ability to self-care improved from 48% to 100% (P = <0.001). The ability to carry out usual activities improved from 13% to 86% (P = <0.001), and the proportion of patients without anxiety and depression increased from 50% to 86% (P > 0.004). However, there was no significant improvement observed in Pain, with only a slight reduction from 57% to 42.8% (P = 0.22). The SGRQ also showed improvements in all dimensions (symptoms, impact, activities) (P < 0.001). However, by the fifth year, the HRQL scores remained below normal reference values. Chronic graft dysfunction was associated with a decline in SGRQ scores. Bilateral LTx patients exhibited better SGRQ scores compared to unilateral LTx patients from the first year post-transplantation. Notably, there were no differences in scores between nonsurvivors and survivors. CONCLUSIONS: The study highlights the long-term improvement in HRQL among LTx patients, with greater improvements observed in physical dimensions compared to psychological dimensions. Bilateral LTx was associated with better SGRQ scores than unilateral LTx, and chronic graft dysfunction primarily affected SGRQ scores. These findings underscore the importance of utilizing both generic and specific HRQL instruments in assessing LTx outcomes.

Prostate cancer patients with lymphatic node involvement detected by immunohistochemistry. Is the effort worthwhile?

INTRODUCTION: Lymph node (LN) status is one of the main prognostic factors in localized prostate cancer (CaP) patients after surgery. Examining palpable lymph nodes with hematoxylin and eosin (HE) is the most common approach in clinical practice; however, immunohistochemistry (IHC) has been reported to increase the LN detection rate. We reviewed the oncological results of patients with LN metastasis detected by IHC. METHODS: Retrospective study of CaP patients who underwent lymphadenectomy at the time of the prostatectomy. Extended lymphadenectomy was performed with complementary indocyanine green (ICG) guidance. Three groups were considered according to LN status. Definition of the pN+ group was made if LNs were detected by HE, occulted lymph node-positive (OLN+) was considered when ≥ 1 LN was identified with IHC and occulted lymph node-negative (OLN-) if no metastatic nodes were found. Oncological outcomes were reported regarding PSA kinetics, biochemical recurrence (BCR), need for secondary treatments and metastasis-free survival (MFS). RESULTS: A total of 283 patients with a median follow-up of 69 months were included in the study. Immunohistochemical assessment revealed metastatic LNs in 8.9% of patients. The rate of locally advanced disease and positive surgical margins was higher in the OLN + and pN + groups vs the OLN - group (P < 0.05). At the end of follow-up, 19%, 44% and 52% of patients from the OLN -, OLN + and pN + groups experienced BCR (P < 0.001), respectively. Additionally, 2.6%, 17% and 22% of patients developed metastatic progression from the OLN -, OLN + and pN+ group (P < 0.001), respectively. In the multivariate analysis, the OLN + group had a higher risk HR: 12 (95% CI, 2.4-56; P = 0.002) of metastatic progression in comparison with OLN - patients. This difference was not observed in the risk of biochemical recurrence HR 1.8 (95% CI, 0.9-3.8; P = 0.09). CONCLUSION: Conventional HE histological analysis underdiagnosed nearly 10% of patients. IHC-detected patients were at higher risk of metastasis development than OLN - patients. This report highlights the importance of optimizing the anatomopathological analysis properly.

Clinical impact of complex percutaneous coronary intervention in the pre-TAVR workup.

INTRODUCTION AND OBJECTIVES: In patients undergoing percutaneous coronary intervention (PCI) in the workup pre-transcatheter aortic valve replacement (TAVR), the clinical impact of coronary revascularization complexity remains unknown. This study sought to examine the impact of PCI complexity on clinical outcomes after TAVR in patients undergoing PCI in the preprocedural workup. METHODS: This was a multicenter study including consecutive patients scheduled for TAVR with concomitant significant coronary artery disease. Complex PCI was defined as having at least 1 of the following features: 3 vessels treated, ≥ 3 stents implanted, ≥ 3 lesions treated, bifurcation with 2 stents implanted, total stent length >60mm, or chronic total occlusion. The rates of major adverse cardiac events (MACE), including cardiovascular mortality, myocardial infarction, and coronary revascularization were evaluated. RESULTS: A total of 1550 patients were included, of which 454 (29.3%) underwent complex PCI in the pre-TAVR workup. After a median follow-up period of 2 [1-3] years after TAVR, the incidence of MACE was 9.6 events per 100 patients-years. Complex PCI significantly increased the risk of cardiac death (HR, 1.44; 95%CI, 1.01-2.07), nonperiprocedural myocardial infarction (HR, 1.52; 95%CI, 1.04-2.21), and coronary revascularization (HR, 2.46; 95%CI, 1.44-4.20). In addition, PCI complexity was identified as an independent predictor of MACE after TAVR (HR, 1.31; 95%CI, 1.01-1.71; P=.042). CONCLUSIONS: In TAVR candidates with significant coronary artery disease requiring percutaneous treatment, complex revascularization was associated with a higher risk of MACE. The degree of procedural complexity should be considered a strong determinant of prognosis in the PCI-TAVR population.

Three-Dimensional Bioprinting of GelMA Hydrogels with Culture Medium: Balancing Printability, Rheology and Cell Viability for Tissue Regeneration.

Three-dimensional extrusion bioprinting technology aims to become a fundamental tool for tissue regeneration using cell-loaded hydrogels. These biomaterials must have highly specific mechanical and biological properties that allow them to generate biosimilar structures by successive layering of material while maintaining cell viability. The rheological properties of hydrogels used as bioinks are critical to their printability. Correct printability of hydrogels allows the replication of biomimetic structures, which are of great use in medicine, tissue engineering and other fields of study that require the three-dimensional replication of different tissues. When bioprinting cell-loaded hydrogels, a small amount of culture medium can be added to ensure adequate survival, which can modify the rheological properties of the hydrogels. GelMA is a hydrogel used in bioprinting, with very interesting properties and rheological parameters that have been studied and defined for its basic formulation. However, the changes that occur in its rheological parameters and therefore in its printability, when it is mixed with the culture medium necessary to house the cells inside, are unknown. Therefore, in this work, a comparative study of GelMA 100% and GelMA in the proportions 3:1 (GelMA 75%) and 1:1 (GelMA 50%) with culture medium was carried out to determine the printability of the gel (using a device of our own invention), its main rheological parameters and its toxicity after the addition of the medium and to observe whether significant differences in cell viability occur. This raises the possibility of its use in regenerative medicine using a 3D extrusion bioprinter.

Risk Factors for Therapeutic Failure and One-Year Mortality in Patients with Intramedullary Nail-Associated Infection after Trochanteric and Subtrochanteric Hip Fracture Repair.

Despite the implications of trochanteric and subtrochanteric intramedullary (IM) nail infection for patients with hip fracture, little is known about risk factors for therapeutic failure and mortality in this population. We performed a retrospective observational analysis including patients diagnosed with trochanteric and subtrochanteric IM nail infection at a Spanish academic hospital during a 10-year period, with a minimum follow-up of 22 months. Of 4044 trochanteric and subtrochanteric IM nail implants, we identified 35 cases of infection during the study period (0.87%), 17 of which were chronic infections. Patients with therapeutic failure (n = 10) presented a higher average Charlson Comorbidity Index (CCI) (5.40 vs. 4.21, p 0.015, CI 0.26-2.13) and higher rates of polymicrobial (OR 5.70, p 0.033, CI 1.14-28.33) and multidrug-resistant (OR 7.00, p 0.027, CI 1.24-39.57) infections. Upon multivariate analysis, polymicrobial infection and the presence of multidrug-resistant pathogens were identified as independent risk factors for therapeutic failure. Implant retention was associated with an increased risk of failure in chronic infection and was found to be an independent risk factor for overall one-year mortality in the multivariate analysis. Our study highlights the importance of broad-spectrum empirical antibiotics as initial treatment of trochanteric and subtrochanteric IM nail-associated infection while awaiting microbiological results. It also provides initial evidence for the importance of implant removal in chronic IM-nail infection.

Design and validation of an artificial intelligence system to detect the quality of colon cleansing before colonoscopy / Diseño y validación de un sistema de inteligencia artificial para detectar la calidad de la limpieza del colon previa a la realización de la colonoscopia

Background and aims Patients’ perception of their bowel cleansing quality may guide rescue cleansing strategies before colonoscopy. The main aim of this study was to train and validate a convolutional neural network (CNN) for classifying rectal effluent during bowel preparation intake as “adequate” or “inadequate” cleansing before colonoscopy.Patients and methodsPatients referred for outpatient colonoscopy were asked to provide images of their rectal effluent during the bowel preparation process. The images were categorized as adequate or inadequate cleansing based on a predefined 4-picture quality scale. A total of 1203 images were collected from 660 patients. The initial dataset (799 images), was split into a training set (80%) and a validation set (20%). The second dataset (404 images) was used to develop a second test of the CNN accuracy. Afterward, CNN prediction was prospectively compared with the Boston Bowel Preparation Scale (BBPS) in 200 additional patients who provided a picture of their last rectal effluent.ResultsOn the initial dataset, a global accuracy of 97.49%, a sensitivity of 98.17% and a specificity of 96.66% were obtained using the CNN model. On the second dataset, an accuracy of 95%, a sensitivity of 99.60% and a specificity of 87.41% were obtained. The results from the CNN model were significantly associated with those from the BBPS (P<0.001), and 77.78% of the patients with poor bowel preparation were correctly classified.ConclusionThe designed CNN is capable of classifying “adequate cleansing” and “inadequate cleansing” images with high accuracy. (AU)

Antecedentes y objetivos La percepción de los pacientes sobre la calidad de su limpieza intestinal puede guiar las estrategias de limpieza de rescate antes de una colonoscopia. El objetivo principal de este estudio fue entrenar y validar una red neuronal convolucional (CNN) para clasificar el efluente rectal durante la preparación intestinal como «adecuado» o «inadecuado».Pacientes y métodosPacientes no seleccionados proporcionaron imágenes del efluente rectal durante el proceso de preparación intestinal. Las imágenes fueron categorizadas como una limpieza adecuada o inadecuada según una escala de calidad de 4 imágenes predefinida. Se recopilaron un total de 1.203 imágenes de 660 pacientes. El conjunto de datos inicial (799 imágenes) se dividió en un conjunto de entrenamiento (80%) y un conjunto de validación (20%). Un segundo conjunto de datos (404 imágenes) se utilizó para evaluar la precisión de la CNN. Posteriormente, la predicción de la CNN se comparó prospectivamente con la escala de preparación colónica de Boston (BBPS) en 200 pacientes que proporcionaron una imagen de su último efluente rectal.ResultadosEn el conjunto de datos inicial, la precisión global fue del 97,49%, la sensibilidad del 98,17% y la especificidad del 96,66%. En el segundo conjunto de datos, se obtuvo una precisión del 95%, una sensibilidad del 99,60% y una especificidad del 87,41%. Los resultados del modelo de CNN se asociaron significativamente con la escala de preparación colónica de Boston (p<0,001), y el 77,78% de los pacientes con una preparación intestinal deficiente fueron clasificados correctamente.ConclusiónLa CNN diseñada es capaz de clasificar imágenes de «limpieza adecuada» y «limpieza inadecuada» con alta precisión. (AU)

Somatostatin: a possible mediator of the long-term effects of experimental vertical gastrectomy on glucose metabolism in rats?

BACKGROUND: Sleeve gastrectomy (SG) is one of the most commonly performed bariatric surgeries. SG treats type 2 diabetes mellitus better than several drugs. The mechanisms that underlie this phenomenon are not clear. This study proposed that somatostatin (SST) isoforms SST-14 and SST-28 are key in the carbohydrate after SG. METHODS: Surgeries were performed on 3 groups of Wistar rats: the fasting, surgery control, and SG groups. Plasma levels of glucose, insulin, SST-14, and SST-28 were measured at 2 survival periods after surgery. Islet SST receptor (SSTR) and cell populations were studied. We performed a pasireotide (SST-28 analogue) infusion assay in another group of rats to confirm the influence of SST-28 plasma levels on the delta-cell population. RESULTS: This study found an elevation in the insulin response after SG in animals but a decrease in the insulin response over the long term with a loss of beta-cell mass. An increase in duodenal SST-28-producing cells in the duodenum and a loss of pancreatic SST-14-producing cells were observed after SG in animals but not in controls. The expression of SSTR type 5 in delta-cell populations from each group and the ability of the pasireotide infusion assay to decrease the delta-cell population indicated the effect of SST-28 plasma levels on delta-cell maintenance. CONCLUSION: After SG initiates a compensatory response in the duodenum, beta-cell mass is depleted after loss of the brake that regulates SST-14 at the paracrine level in a nonobese, normoglycemic rat model. This was an experimental model, with no clinical translation to the human clinic, with a preliminary importance regarding new pathophysiologic perspectives or pathways.