Virtual tissue microstructure reconstruction across species using generative deep learning.

Analyzing tissue microstructure is essential for understanding complex biological systems in different species. Tissue functions largely depend on their intrinsic tissue architecture. Therefore, studying the three-dimensional (3D) microstructure of tissues, such as the liver, is particularly fascinating due to its conserved essential roles in metabolic processes and detoxification. Here, we present TiMiGNet, a novel deep learning approach for virtual 3D tissue microstructure reconstruction using Generative Adversarial Networks and fluorescence microscopy. TiMiGNet overcomes challenges such as poor antibody penetration and time-intensive procedures by generating accurate, high-resolution predictions of tissue components across large volumes without the need of paired images as input. We applied TiMiGNet to analyze tissue microstructure in mouse and human liver tissue. TiMiGNet shows high performance in predicting structures like bile canaliculi, sinusoids, and Kupffer cell shapes from actin meshwork images. Remarkably, using TiMiGNet we were able to computationally reconstruct tissue structures that cannot be directly imaged due experimental limitations in deep dense tissues, a significant advancement in deep tissue imaging. Our open-source virtual prediction tool facilitates accessible and efficient multi-species tissue microstructure analysis, accommodating researchers with varying expertise levels. Overall, our method represents a powerful approach for studying tissue microstructure, with far-reaching applications in diverse biological contexts and species.

Phenotypic characterization of liver tissue heterogeneity through a next-generation 3D single-cell atlas.

Three-dimensional (3D) geometrical models are potent tools for quantifying complex tissue features and exploring structure-function relationships. However, these models are generally incomplete due to experimental limitations in acquiring multiple (> 4) fluorescent channels in thick tissue sections simultaneously. Indeed, predictive geometrical and functional models of the liver have been restricted to few tissue and cellular components, excluding important cellular populations such as hepatic stellate cells (HSCs) and Kupffer cells (KCs). Here, we combined deep-tissue immunostaining, multiphoton microscopy, deep-learning techniques, and 3D image processing to computationally expand the number of simultaneously reconstructed tissue structures. We then generated a spatial single-cell atlas of hepatic architecture (Hep3D), including all main tissue and cellular components at different stages of post-natal development in mice. We used Hep3D to quantitatively study 1) hepatic morphodynamics from early post-natal development to adulthood, and 2) the effect on the liver's overall structure when changing the hepatic environment after removing KCs. In addition to a complete description of bile canaliculi and sinusoidal network remodeling, our analysis uncovered unexpected spatiotemporal patterns of non-parenchymal cells and hepatocytes differing in size, number of nuclei, and DNA content. Surprisingly, we found that the specific depletion of KCs results in morphological changes in hepatocytes and HSCs. These findings reveal novel characteristics of liver heterogeneity and have important implications for both the structural organization of liver tissue and its function. Our next-gen 3D single-cell atlas is a powerful tool to understand liver tissue architecture, opening up avenues for in-depth investigations into tissue structure across both normal and pathological conditions.

A narrative on diversity, equity, and inclusion in surgery: insights from the European Society of Coloproctology and identification of points for action.

The focus of the 2022 European Society of Coloproctology (ESCP) annual campaign was diversity, equity, and inclusion (DEI) in surgery. The ESCP "Operation Equal Access" campaign sought to interview key-opinion leaders and trainees, to raise awareness on inequalities, inform the community of the status of the topic, and to identify future areas for improvement. The ESCP Social Media Working Group interviewed experts who have made significant contributions to DEI in colorectal surgery and were acknowledged opinion leaders in the field. The interviews focused on their career, professional life, experiences, and opportunities during their training, and their views on DEI in colorectal surgery. DEI principles, education, and values need further promotion to reduce and address bias within the profession and overall improve the experience of minority community including health professionals and patients. International Societies are working to facilitate training opportunities and overcome DEI, and networking have contributed to that. Collaborations between societies will be pivotal to contribute to offering research and leadership opportunities equally. Access to advanced workshops including cadaveric training and simulation can be consistently promoted and provided globally via societies through telemonitoring. Involving patients in research should be encouraged, as it brings the perspective of a living experience.

Efecto de un entrenamiento con ejercicios de autocarga a alta velocidad en el equilibrio dinámico y estático en mujeres adultas mayores / Effect of a high-speed bodyweight resistance training on timed up and go and one leg stance in older women

Background: High-speed resistance training programs aiming to increase muscle power have beneficial effects on balance. Aim: To compare the effect of high-speed bodyweight resistance training and normal-speed bodyweight resistance training on the static and dynamic balance in community-dwelling older women. Material and Methods: Thirty-five non-disabled community-dwelling women aged 65 to 80 years were trained for 12 weeks using a high-speed bodyweight resistance training (HS-BT) or a normal-speed bodyweight resistance training (NS-BT). At baseline and after the intervention, One Leg Stance (OLS) and Timed Up and Go (TUG) tests were measured. Participants with an attendance to training sessions of less than 70% were excluded from the final analysis. Results: Data from 26 participants were analyzed, 14 women aged 71 ± 4 years who received HS-BT and 12 women aged 73 ± 4 years who received NS-BT. After 12 weeks of training, a significant improvement in TUG was observed in women receiving HS-BT (ΔTUG −1.07 sec, p < 0.01), but without changes in the OLS test. No significant changes were observed in any of the tests in the NS-BT group. Conclusions: High-speed bodyweight resistance training for 12 weeks improved TUG in these women.

[Effect of a high-speed bodyweight resistance training on timed up and go and one leg stance in older women]. / Efecto de un entrenamiento con ejercicios de autocarga a alta velocidad en el equilibrio dinámico y estático en mujeres adultas mayores.

BACKGROUND: High-speed resistance training programs aiming to increase muscle power have beneficial effects on balance. AIM: To compare the effect of high-speed bodyweight resistance training and normal-speed bodyweight resistance training on the static and dynamic balance in community-dwelling older women. MATERIAL AND METHODS: Thirty-five non-disabled community-dwelling women aged 65 to 80 years were trained for 12 weeks using a high-speed bodyweight resistance training (HS-BT) or a normal-speed bodyweight resistance training (NS-BT). At baseline and after the intervention, One Leg Stance (OLS) and Timed Up and Go (TUG) tests were measured. Participants with an attendance to training sessions of less than 70% were excluded from the final analysis. RESULTS: Data from 26 participants were analyzed, 14 women aged 71 ± 4 years who received HS-BT and 12 women aged 73 ± 4 years who received NS-BT. After 12 weeks of training, a significant improvement in TUG was observed in women receiving HS-BT (ΔTUG -1.07 sec, p < 0.01), but without changes in the OLS test. No significant changes were observed in any of the tests in the NS-BT group. CONCLUSIONS: High-speed bodyweight resistance training for 12 weeks improved TUG in these women.

Tumores neuroendocrinos primarios de colon y recto / Primary neuroendocrine tumors of the colon and rectum

Resumen Introducción La clasificación y el manejo de los tumores neuroendocrinos (TNEs) han cambiado drásticamente en la última década. Se realiza un análisis crítico del manejo de los TENs colorrectales primarios intervenidos en nuestro centro a la luz de la nueva clasificación. Material y Método Análisis retrospectivo de los resultados del tratamiento quirúrgico radical de este tipo de lesiones en un período de 15 años. Resultados Se trata de 10 pacientes, con un promedio de 56 años (extremos 48-76), 6 ubicados cercanos a la válvula ileocecal (VIC) que se presentaron con un cuadro de obstrucción intestinal incompleto y tres en el recto (2 pólipos) y un pólipo en colon sigmoides. La cirugía efectuada incluye cuatro resecciones anteriores y seis colectomías derechas (con resección de una metástasis hepática en 1 caso). La mediana de seguimiento fue de 78,3 meses (extremos 8-180), durante el cual dos pacientes fallecen por metástasis a distancia. Conclusión Los TNEs ubicados en el colon habitualmente se presentaron como grandes masas tumorales cercanos a la VIC, lo que proporcionalmente no ocurre con las lesiones del rectosigmoides que son diagnosticados más precozmente como pólipos o lesiones submucosas. Algunos tumores de bajo grado muestran un compromiso avanzado en la pared y/o los linfonodos regionales lo que justifica la resección radical y/o la quimioterapia adyuvante. A la luz de esta experiencia, es necesario complementar el grado del tumor OMS 2010 (Ki-67 y número de mitosis) con el estadio TNM para caracterizar adecuadamente los TNEs, lo que influye en el manejo multidisciplinario.

Background The nomenclature and staging classification of neuroendocrine tumors (NETs) has changed drastically in the past decade. Objective To do a critical analysis of management of colorectal NETs in our institution in the light of the new classification. Methods We retrospectively reviewed the records of consecutive patients operated on with radical intention due to a colorectal NET in the last 15 years. Results There were 10 patients, median age was 56 years (range 48-76), six of them located near the ileocecal valve, three in the rectum (2 of them polyps) and one polyp in the sigmoid colon. Surgical procedure included four anterior resections and six right colectomy (one with hepatic resection). The median follow up was 78.3 months (range 8-180). Two patients died due to metastatic disease. Conclusion NETs located near de ileocecal valve were diagnosed usually as a big tumor with obstructing symptoms, while NETs of the rectum and sigmoid colon more frequently were detected as polyps or submucosal lesions. Some low grade TENs may invade the colonic wall and/or have metastasis in the regional lymph nodes and those cases need radical resection and/or adjuvant therapy. Combine the grade (Ki-67 and number and/or number of mitosis) of 2010 WHO classification with TNM showed prognostic value for classification and staging colorectal NETs with important therapeutic implications.

Rectosigmoidectomía perineal para el tratamiento del prolapso rectal completo / Perineal rectosigmoidectomy for the treatment of rectal prolapse

Objetivo: Presentamos nuestra experiencia en el tratamiento quirúrgico de esta patología con la técnica de la rectosigmoidectomía perineal. Material y método: Se trata de una serie retrospectiva, consecutiva de 17 pacientes. Resultados: Predomina el género femenino y el promedio de edad es de 62 años. La morbilidad alcanza el 23%, aunque casi toda de menor gravedad, con solo un paciente reoperado. La recidiva es del 6%, con mejoría de los síntomas en un 88%. Conclusión: Concluimos que es una técnica segura, con una morbilidad controlada y con buenos resultados a mediano plazo con un adecuado control de la recidiva y mejoría de la continencia en un alto porcentaje de los pacientes.

Aim: We present our experience with perineal rectosigmoidectomy for the treatment of rectal prolapse. Material and method: It is a retrospective, consecutive series of 17 patients. Results: Predominantly female and the average age is 62 years. Morbidity reached 23%, but almost all less serious, with only one reoperation. Recurrence is 6%, and the improvement in continence is 88%. Conclusion: We conclude that it is a safe technique with a controlled morbidity and good results with low recurrence and improvement of continence in a high percentage of patients.

Exenteración pélvica total por cáncer primario del recto: resultados inmediatos y alejados / Total pelvic exenteration for locally advanced rectal tumors: experience in 10 patients

Objetivo: El objetivo de este estudio es mostrar los resultados inmediatos y alejados de la exenteración pélvica total (EPT) en el manejo de tumores primarios de recto localmente avanzados. Se describe una alternativa técnica en los casos de EPT supraelevador. La EPT puede ser la única oportunidad de curación en pacientes con tumores pélvicos de gran volumen. Material y método: Se incluyen tumores T4 por la estadificación clínica o los hallazgos operatorios sometidos a una EPT con intención curativa. Resultados: En un periodo de 16 años se intervienen con esta técnica 10 pacientes, 6 de los cuales recibieron radioquimioterapia neoadyuvante. La técnica clásica se empleó en 3 pacientes y la EPT supraelevador, en 6. El promedio de hospitalización fue de 36 días (rango, 18-97) y la morbilidad alcanzó el 80%. El estudio de la pieza operatoria confirmó un tumor T4 en 6 pacientes, T3 en 3 y T0 en uno. Los 6 pacientes con neoadyuvancia son 1 ypT0N0M0, 2 ypIIA, 2 ypIIC y 1 ypIIIB. El resto eran 2 pIIC y 2 pIIIC. En el seguimiento hay 5 pacientes vivos entre 30 y 180 meses, y 3 fallecen por metástasis a distancia sin recidiva local. Conclusión: La EPT es una intervención asociada a una elevada morbilidad y larga estadía hospitalaria. La EPT supraelevador protegida mediante una ileostomía transitoria evitó una colostomía definitiva en 6 de 10 casos. La ileostomía urinaria muestra resultados funcionales satisfactorios en el largo plazo. La sobrevida prolongada en la mitad de los pacientes justifica la indicación de la técnica en casos seleccionados.

Aim: To report the results of total pelvic exenteration (TPE) in patients with locally advanced primary rectal tumors. Material and method: We report 10 patients with stage 4 rectal tumors subjected to a potentially curative TPE in a period of 16 years. Results: Six patients received also adjuvant chemoradiotherapy. A classic technique was used in 3 patients and a supra-elevator technique in 6. Mean hospitalization length was 36 days, and 80% of patients had complications. The pathological study of the surgical piece confirmed a T4 tumor in 6 patients, T3 in 3 and T0 in one. Among patients who received chemoradiotherapy, one was in stage ypT0N0M0, 2 in ypIIA, 2 in ypIIC, one in ypIIIB, 2 in pIIC and 2 in pIIIC. During follow up 3 patients survived between 30 and 180 months and three died due to distant metastases without local relapse. Conclusion: TPE requires long hospital stays and has a high rate of complications. Supra-elevator TPE protected with a transitory ileostomy avoided definitive colostomy in 6 of 10 cases. Urinary ileostomy had satisfactory long term functional results. The prolonged survival of half of the patients justifies the use of this surgical technique.

Levels of moderate--vigorous physical activity are low in Spanish children with cystic fibrosis: a comparison with healthy controls.

BACKGROUND: Physical activity (PA) is recommended as part of the treatment regimen for cystic fibrosis (CF) although objective methods have been scarcely used to monitor achievement of PA guidelines. METHODS: PA was measured by accelerometer in outpatient CF children (n=47) and results were compared with those obtained in age- and gender-matched healthy controls (n=39). RESULTS: 2.1% of the outpatients fulfilled PA guidelines (i.e. ≥60min·day(-1) of moderate-to-vigorous PA (MVPA)) vs. 34.2% of controls. Overall, lower MVPA levels were observed in CF patients than controls despite the former undergoing more light or total PA. Peak oxygen uptake was also lower in the CF group than in controls (37.5±7.8 vs. 43.5±7.6ml·kg(-1)·min(-1), p=0.002) and was correlated with MVPA and vigorous PA in the former. CONCLUSIONS: These findings support a need to promote PA interventions (including MVPA) targeted at improving cardiorespiratory fitness in CF children.

Obesity and physical activity patterns in children and adolescents.

AIM: The aim of this study is to measure objectively and accurately the physical activity (PA) patterns in Spanish children and adolescents according to their obesity status, gender and age groups. METHODS: A sample of 487 children and 274 adolescents from the European Youth Heart Study participated in the study. The variables measured were anthropometric characteristics (height, weight and body mass index), and PA was measured during 6 consecutive days using the GT1M accelerometer. RESULTS: Three-way analysis of variance (age × gender × obesity status) showed significant differences in the interaction effect in age, gender and obesity status (normal-weight and overweight/obesity) for mean of moderate-to-vigorous PA (MVPA) (P = 0.02) and vigorous PA (VPA) (P = 0.014) within the sample. Nine-year-old normal-weight children achieved significantly (P < 0.05) more MVPA on weekdays than 9-year-old overweight/obesity children. During weekend days, all sample achieved significant more MVPA (P < 0.01) and significant more VPA (P < 0.05) than during weekdays. Few children (37.5% of 9-year-old normal-weight and 34.0% of 9-year-old overweight/obese) and adolescents (16.4% and 27.3% normal-weight and overweight/obese, respectively) met the current health-related recommendations of 60 min of MVPA daily. CONCLUSIONS: It is clear that activity levels are insufficient for all children, in particular overweight/obese children and adolescents, although the precise nature of the relationship appears to differ between boys and girls.

Health-related quality of life of Spanish children with cystic fibrosis.

PURPOSE: To investigate (1) the contributions of sex, age, nutritional status- and physical-fitness-related variables on health-related quality of life (HRQOL) in Spanish children with cystic fibrosis, and (2) the agreement on HRQOL between children and their parents. METHODS: In 28 children aged 6-17 years, body mass index percentile, percentage body fat, physical activity, pulmonary function, cardiorespiratory fitness, functional mobility, and dynamic muscle strength were determined using objective measures. HRQOL was measured using the revised version of the cystic fibrosis questionnaire. Simple and multiple linear regression analyses were performed to determine the variables associated with HRQOL. To assess the agreement on HRQOL between children and parents, intra-class correlation coefficients (ICCs) were calculated. RESULTS: Girls reported worse emotional functioning, a higher treatment burden, and more respiratory problems than boys. Greater functional mobility appeared associated with a less favourable body image and more eating disturbances. Agreement on HRQOL between children and parents was good to excellent, except for the domain of treatment burden. CONCLUSIONS: Sex and age were stronger predictors of HRQOL than nutritional status- or physical-fitness-related variables. Children reported a lower treatment burden than their parents perceived them to have.

Short-term, light- to moderate-intensity exercise training improves leg muscle strength in the oldest old: a randomized controlled trial.

OBJECTIVES: To assess the effects of an 8-week exercise training program with a special focus on light- to moderate-intensity resistance exercises (30-70% of one repetition maximum, 1RM) and a subsequent 4-week training cessation period (detraining) on muscle strength and functional capacity in participants aged 90 and older. DESIGN: Randomized controlled trial performed during March to September 2009. SETTING: Geriatric nursing home. PARTICIPANTS: Forty nonagenarians (90-97) were randomly assigned to an intervention or control group (16 women and 4 men per group). INTERVENTION: Eight-week muscle strength exercise intervention focused on lower limb strength exercises of light to moderate intensity. PRIMARY OUTCOME: 1RM leg press. SECONDARY OUTCOMES: handgrip strength, 8-m walk test, 4-step stairs test, Timed Up and Go test, and number of falls. RESULTS: A significant group by time interaction effect (P=.02) was observed only for the 1RM leg press. In the intervention group, 1RM leg press increased significantly with training by 10.6 kg [95% confidence interval (CI)=4.1-17.1 kg; P=.01]. Except for the mean group number of falls, which were 1.2 falls fewer per participant in the intervention group (95% CI=0.0-3.0; P=.03), no significant training effect on the secondary outcome measures was found. CONCLUSION: Exercise training, even of short duration and light to moderate intensity, can increase muscle strength while decreasing fall risk in nonagenarians.

Does resistance training improve the functional capacity and well being of very young anorexic patients? A randomized controlled trial.

PURPOSE: We determined the effects of a 3-month low-moderate-intensity strength training program (2 sessions/week) on functional capacity, muscular strength, body composition, and quality of life (QOL) in 22 young (12-16 yrs) anorexic outpatients. METHODS: Patients were randomly assigned to a training or control group (n=11 [10 females] each). Training sessions were of low intensity (loads for large muscle groups ranging between 20%-30% and 50%-60% of six repetitions maximum [6RM] at the end of the program). We measured functional capacity by the time up and go and the timed up and down stairs tests. Muscular strength was assessed by 6RM measures for seated bench and leg presses. We estimated percent body fat and muscle mass. We assessed patients' QOL with the Short Form-36 items. RESULTS: The intervention was well tolerated and did not have any deleterious effect on patients' health, and did not induce significant losses in their body mass. The only studied variable for which a significant interaction (group x time) effect was found (p=.009) was the 6RM seated lateral row test. CONCLUSIONS: Low-moderate-intensity strength training does not seem to add major benefits to conventional psychotherapy and refeeding treatments in young anorexic patients.

Health enhancing strength training in nonagenarians (STRONG): rationale, design and methods.

BACKGROUND: The Health Enhancing Strength Training in Nonagenarians (STRONG) is a randomised control trial to assess the effectiveness of an aerobic and strength training program for improving muscle strength, functional capacity and quality of life in nonagenarians. METHODS: Sixty (51 women) nonagenarians (age range: 90-102 years) who live in a geriatric nursing home will be randomly assigned to either a usual care (control) group (n = 30) or an intervention (training) group (n = 30). Participants allocated in the usual care group will receive general physical activity guidelines and participants allocated in the intervention group will also enroll in three weekly non-consecutive individualized training sessions (approximately 45-50 min each) during 8 weeks. The exercise program will consist of muscular strength [with a special focus on leg press at 30% (start of the program) to 70% 1 repetition maximum (end)] and aerobic exercises (cycle-ergometry during 3-5 to 15 minutes at 12-14 points in the rate of perceived exertion scale). RESULTS: Results from STRONG will help to better understand the potential of regular physical activity for improving the well-being of the oldest population groups. CONCLUSION: The increase in life expectancy together with the dramatic decrease in birth rates in industrialized countries calls the attention to health care systems and public health policymakers to focus attention on promoting healthy lifestyle in the highest sector of the population pyramid. Our study attempts to improve functional capacity and QOL of nonagenarians by implementing an individualised aerobic and strength training program in a geriatric residential care. Results from STRONG will help to better understand the potential of regular physical activity for improving the well being even in persons aged 90 years or over.