Dynamics of mitochondrial membranes under photo-oxidative stress with high spatiotemporal resolution.

In our study, we harnessed an original Enhanced Speed Structured Illumination Microscopy (Fast-SIM) imaging setup to explore the dynamics of mitochondrial and inner membrane ultrastructure under specific photo-oxidation stress induced by Chlorin-e6 and light irradiation. Notably, our Fast-SIM system allowed us to observe and quantify a distinct remodeling and shortening of the mitochondrial structure after 60-80 s of irradiation. These changes were accompanied by fusion events of adjacent inner membrane cristae and global swelling of the organelle. Preceding these alterations, a larger sequence was characterized by heightened dynamics within the mitochondrial network, featuring events such as mitochondrial fission, rapid formation of tubular prolongations, and fluctuations in cristae structure. Our findings provide compelling evidence that, among enhanced-resolution microscopy techniques, Fast-SIM emerges as the most suitable approach for non-invasive dynamic studies of mitochondrial structure in living cells. For the first time, this approach allows quantitative and qualitative characterization of successive steps in the photo-induced oxidation process with sufficient spatial and temporal resolution.

Changes in attitudes to awareness of hypoglycaemia during a hypoglycaemia awareness restoration programme are associated with avoidance of further severe hypoglycaemia episodes within 24 months: the A2A in HypoCOMPaSS study.

AIMS/HYPOTHESIS: The aims of this study were to assess cognitions relating to hypoglycaemia in adults with type 1 diabetes and impaired awareness of hypoglycaemia before and after the multimodal HypoCOMPaSS intervention, and to determine cognitive predictors of incomplete response (one or more severe hypoglycaemic episodes over 24 months). METHODS: This analysis included 91 adults with type 1 diabetes and impaired awareness of hypoglycaemia who completed the Attitudes to Awareness of Hypoglycaemia (A2A) questionnaire before, 24 weeks and 24 months after the intervention, which comprised a short psycho-educational programme with optimisation of insulin therapy and glucose monitoring. RESULTS: The age and diabetes duration of the participants were 48±12 and 29±12 years, respectively (mean±SD). At baseline, 91% reported one or more severe hypoglycaemic episodes over the preceding 12 months; this decreased to <20% at 24 weeks and after 24 months (p=0.001). The attitudinal barrier 'hyperglycaemia avoidance prioritised' (η2p=0.250, p=0.001) decreased from baseline to 24 weeks, and this decrease was maintained at 24 months (mean±SD=5.3±0.3 vs 4.3±0.3 vs 4.0±0.3). The decrease in 'asymptomatic hypoglycaemia normalised' from baseline (η2p=0.113, p=0.045) was significant at 24 weeks (1.5±0.3 vs 0.8±0.2). Predictors of incomplete hypoglycaemia response (one or more further episodes of severe hypoglycaemia) were higher baseline rates of severe hypoglycaemia, higher baseline scores for 'asymptomatic hypoglycaemia normalised', reduced change in 'asymptomatic hypoglycaemia normalised' scores at 24 weeks, and lower baseline 'hypoglycaemia concern minimised' scores (all p<0.05). CONCLUSIONS/INTERPRETATION: Participation in the HypoCOMPaSS RCT was associated with improvements in hypoglycaemia-associated cognitions, with 'hyperglycaemia avoidance prioritised' most prevalent. Incomplete prevention of subsequent severe hypoglycaemia episodes was associated with persistence of the cognition 'asymptomatic hypoglycaemia normalised'. Understanding and addressing cognitive barriers to hypoglycaemia avoidance is important in individuals prone to severe hypoglycaemia episodes. CLINICAL TRIALS REGISTRATION: www.isrctn.org : ISRCTN52164803 and https://eudract.ema.europa.eu : EudraCT2009-015396-27.

Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena / Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort

Introducción: El diagnóstico de enfermedad inflamatoria intestinal (EII) se realiza, en un alto porcentaje, durante la edad reproductiva. La EII en remisión es el mejor escenario para planificar el embarazo. Objetivos: Describir las características clínicas del embarazo y del recién nacido, evaluando la actividad de la enfermedad en el momento de la concepción y en la evolución del embarazo en un centro terciario en Chile. Métodos: Estudio observacional, retrospectivo, incluyó a mujeres con EII que habían tenido un parto durante 2017-2020. Los datos demográficos, clínicos y obstétricos se obtuvieron del Registro de EII. Se realizó análisis estadístico descriptivo y de asociación (χ2, p ≤ 0,05). Resultados: Se incluyeron 60 mujeres en el estudio. Al inicio del embarazo, 21 (35%) presentaban actividad inflamatoria y 39 (65%) estaban en remisión. Del grupo con actividad, 16 (66%) permanecieron activas y seis tuvieron un aborto espontáneo. Aquellas en remisión, 26 (69%) permanecieron en esta condición; nueve pacientes (15%) habían suspendido el tratamiento, seis de las cuales presentaron actividad durante el embarazo. El consejo preconcepcional fue realizado en 23/60 pacientes, siendo mayor en el grupo que permaneció en remisión durante el embarazo (65% vs. 35%, p = 0,02). Pacientes con brotes durante el embarazo tuvieron mayor probabilidad de embarazo pretérmino (< 37 semanas) y recién nacido de menor peso comparado con el grupo que permaneció en remisión (89 vs. 74%; p = 0,161) y (2,885 vs. 3,370 g; p = 0,0014), respectivamente. Conclusión: La remisión durante el embarazo presenta los mejores resultados y el consejo preconcepcional permite un mejor control de la EII durante el embarazo.(AU)

Background: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. Aims: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. Methods: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). Results: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). Conclusion: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.(AU)

Pregnancy in Inflammatory Bowel Disease: Experience of a Chilean cohort. / Embarazo en enfermedad inflamatoria intestinal: experiencia en una cohorte chilena.

BACKGROUND: In inflammatory bowel disease (IBD) a high percentage of women are diagnosed during their reproductive age. IBD in remission is the ideal scenario when planning a pregnancy. AIMS: To describe the clinical characteristics of pregnancy/newborn and assess disease activity at the time of conception and throughout the pregnancy in patients with IBD treated at a tertiary centre in Chile. METHODS: We retrospectively reviewed women diagnosed with IBD who were pregnant or delivered between 2017 and 2020. Demographic, clinical, obstetric and delivery data were obtained from the IBD registry, approved by the local IRB. Descriptive statistics and association tests were performed (χ2, p ≤ 0.05). RESULTS: Sixty women with IBD were included. At the beginning of pregnancy, 21 (35%) had active disease and 39 (65%) were in remission. Of those with active disease, 16 (66%) remained active and 6 had spontaneous abortions. In those who were in remission, 26 (69%) remained in this condition. Nine patients (15%) discontinued treatment, and 6 of these had inflammatory activity during pregnancy. Preconception counselling was performed in 23 of the 60 patients, being higher in the group that remained in remission during pregnancy (65% vs. 35%, p = 0.02). Patients who had a flare during pregnancy had more probability of preterm birth (<37 weeks) and newborn with lower weight compared with the group that always remained in remission (89% vs. 74%, p = 0.161) and (2.885 vs 3.370 g; p = 0.0014). CONCLUSION: Remission presents better outcomes in pregnancy and preconception counselling would allow a better IBD control during pregnancy.

Differentiating Hypoglycemia Awareness Status from Hypoglycemia Experience in Tools for Measuring Impaired Awareness of Hypoglycemia.

Background: Developing technologies in real-time continuous glucose monitoring (CGM) are successfully reducing severe hypoglycemia (SH) in trials and clinical practice. Their impact on impaired awareness of hypoglycemia, a major risk factor for SH, is uncertain. Methods: The present study examined two scales for assessing hypoglycemia awareness status, the Gold score and the eight-item Minimally Modified Clarke Hypoglycemia Survey (MMCHS), commonly used in trials of CGM, in Portuguese-speaking adults with type 1 diabetes and conducted an exploratory factor analysis on MMCHS. Results: A bifactorial structure in MMCHS was revealed, with a clear distinction between items that measure SH experience and those that measure hypoglycemia awareness status. The latter is associated with the same risk for SH as the Gold score. Conclusions: We conclude that improvement in awareness scores by the MMCHS may reflect only a reduction in SH with no restoration of endogenous awareness, making the current literature consistent in evidence that CGM does not improve endogenous awareness and nonsensor supported protection from SH. This has implications for risk of SH when CGM is not being worn.

Características antropométricas, fisiológicas y funcionales en jugadores profesionales de rugby seven / Anthropometric, physiological and functional characteristics in professional rugby seven players

El desarrollo de cualidades específicas en jugadores de rugby seven optimiza su desempeño. El objetivo de este trabajo es la caracterización de las cualidades antropométricas, fisiológicas y funcionales en jugadores profesionales de ese deporte mediante un estudio transversal en catorce seleccionados nacionales de rugby seven. Se rescataron datos demográficos, tácticos, antropométricos (índice de masa corporal (IMC) y composición corporal), fisiológicos (consumo de oxígeno ­VO2­) y funcionales (Running-based Anaerobic Sprint Test (RAST) y saltos verticales (Squat Jump (SJ) y Counter Movement Jump ­CMJ­).Se comparó a los atletas según posición de juego (forwards y backs) con prueba de Mann-Whitney y Fisher y se buscaron asociaciones entre variables demográficas y resultados funcionales con regresión lineal simple y ANOVA (significancia: p<0.05).La media de edad fue 23.5 años (22-29), y la del IMC 26.6 kg/m2 (23.4-33.3), mayor en forwards (p=0.005). El porcentaje de masa grasa corporal fue 17.5% (15.7-21.9), sin diferencias por posición.El VO2 fue mayor en backs (p=0.035). La prueba de saltabilidad no tuvo diferencias en potencia relativa (p=0.807), la potencia máxima mostró una tendencia mayor en forwards (p=0.086).Se evidenció que por cada año de edad la velocidad VO2 máxima disminuyó en 0.14 m/s (p=0.05). Por cada punto de IMC, la velocidad VO2 máxima disminuyó en 0.2 m/s (p=0.007), y el VO2 máximo disminuyó en 1.21 ml/kg/min (p=0.001).Consumir tabaco mostró una tendencia a aumentar en 4 w/kg el índice de fatiga (p=0.094), 21.4% eran fumadores.Una mayor edad e IMC se asocian con peor desempeño funcional en atletas de rugby seven. Los forwards presentaron mayor IMC y menor VO2.Tipo de estudio: Estudio transversal. Nivel de evidencia: III

Developing specific abilities in Rugby Seven players optimizes their game performance.Characterize anthropometric, physiological and functional qualities of Rugby Seven professional athletes.Cross-sectional study, fourteen rugby seven athletes of the national team were recruited. Demographic, tactical and anthropometric data (body mass index (BMI) and composition) were obtained. The following outcomes were evaluated: physiological parameters (oxygen consumption ­VO2­) and functional parameters (Running-based Anaerobic Sprint Test, vertical jumps (Single Squat Jump-Counter Movement Jump ­CMJ­).Athletes were grouped according to their game position (forwards and backs) for comparison (Mann-Whitney and Fisher's test).A simple linear regression and ANOVA were used to establish association between demographic variables and functional outcomes (significance: p<0.05; suggestion: p<0.1).Median age was 23.5 years (22-29), and median BMI was 26.6 kg/m2 (23.4-33.3), higher in forwards (p=0.005). KERR fat was 17.5% (15.7-21.9), without difference according to game position.Maximum oxygen consumption (VO2 max) was 54.8 ml/kg/min (48.2-61), higher in backs (p=0.035). Jumping tests showed no difference in the relative power (p=0.807), muscular peak power showed a tendency to be higher in forwards (p=0.086).For each year of age increased, the VO2 max speed decreased in 0.14 m/s (p=0.05). For each BMI point increased, the VO2 max speed decreased in 0.2 m/s (p=0.007), and the VO2 max decreased in 1.21 ml/kg/min (p=0.001). Smoking showed a tendency to increase the fatigue index in 4 w/kg (p=0.094); 21.4% were smokers.Older age and BMI are associated with poorer functional performance in these athletes. Forwards show higher percentage of BMI and lower VO2. Type of study: Cross-sectional study. Level of evidence: III

Kinetics and Mechanism of the Arase-Hoshi R2BH-Catalyzed Alkyne Hydroboration: Alkenylboronate Generation via B-H/C-B Metathesis.

The mechanism of R2BH-catalyzed hydroboration of alkynes by 1,3,2-dioxaborolanes has been investigated by in situ 19F NMR spectroscopy, kinetic simulation, isotope entrainment, single-turnover labeling (10B/2H), and density functional theory (DFT) calculations. For the Cy2BH-catalyzed hydroboration 4-fluorophenylacetylene by pinacolborane, the resting state is the anti-Markovnikov addition product ArCH = CHBCy2. Irreversible and turnover-rate limiting reaction with pinacolborane (k ≈ 7 × 10-3 M-1 s-1) regenerates Cy2BH and releases E-Ar-CH═CHBpin. Two irreversible events proceed in concert with turnover. The first is a Markovnikov hydroboration leading to regioisomeric Ar-C(Bpin)═CH2. This is unreactive to pinacolborane at ambient temperature, resulting in catalyst inhibition every ∼102 turnovers. The second is hydroboration of the alkenylboronate to give ArCH2CH(BCy2)Bpin, again leading to catalyst inhibition. 9-BBN behaves analogously to Cy2BH, but with higher anti-Markovnikov selectivity, a lower barrier to secondary hydroboration, and overall lower efficiency. The key process for turnover is B-H/C-B metathesis, proceeding by stereospecific transfer of the E-alkenyl group within a transient, µ-B-H-B bridged, 2-electron-3-center bonded B-C-B intermediate.

Trastorno facticio aplicado a otro: doble caso con un resultado de muerte / Factitious disorder imposed on another: double case with a result of death

Presentamos el caso fatal de un lactante intoxicado con tramadol, detectado en hueso después de 28 meses de intervalo posmortem, tras estudio ordenado por la fiscalía por síntomas similares en un hermano superviviente. Las intoxicaciones se produjeron durante su hospitalización por un síndrome convulsivo idiopático y refractario a tratamiento, en el contexto de un trastorno facticio aplicado a otro. Se analiza el modo de presentación del caso, la importancia del equipo de salud en la detección precoz y el enfoque médico-legal para el diagnóstico final (AU)

We present the fatal case of an infant intoxicated with Tramadol detected in bone after an interval of twenty-eight months post mortem, after study ordered by the prosecutor for similar symptoms in a surviving brother. Intoxications occurred during their hospitalization for an idiopathic, convulsive and refractory syndrome to treatment, in the context of a Factitious Disorder imposed on another. We analyze mode of presentation for the case, the importance of health team in early detection and forensic approach for final diagnosis (AU)

Prevalencia de maloclusiones en escolares de 6 y 12 Años de Choshuenco - Neltume, Chile / Prevalence of malocclusion in 6 and 12 year-old schoolchildren from Choshuenco - Neltume, Chile

Para desarrollar estrategias preventivas e interceptivas en ortodoncia es necesario conocer la prevalencia de maloclusiones de la población en la cual se pretenden instaurar estas medidas. El objetivo de este estudio fue determinar la prevalencia de maloclusiones en escolares de 6 y 12 años de las localidades de Choshuenco y Neltume en el año 2015 pertenecientes a la comuna de Panguipulli, Chile. Se realizó un estudio observacional descriptivo de carácter censal. La muestra total fue de 91 niños y adolescentes matriculados en establecimientos educacionales de las localidades de Choshuenco y Neltume. Se realizó un examen clínico visual para determinar el número de maloclusiones por individuo de acuerdo al método de Björk et al. (1964). Para el análisis de los datos se realizó estadística descriptiva utilizando el programa Excel. Se encontró una prevalencia de maloclusiones de un 60 % escolares de 6 años y de un 91.3% en escolares de 12 años. Los datos de prevalencia superan lo reportado a nivel nacional por lo que es necesario reforzar las medidas promocionales en la población y potenciar el accionar preventivo ­ interceptivo que se desarrolla en estas localidades.

To develop preventive and interceptive strategies in orthodontics is necessary to know the prevalence of malocclusion of the population in which is intended to introduce these measures. The aim of this study was to determine the prevalence of malocclusion in schoolchildren of 6 and 12 year-old from Choshuenco and Neltume 2015, belonging to the commune of Panguipulli, Chile. A descriptive study of census was conducted. The total sample was 91 children and adolescents enrolled in educational institutions in the towns of Choshuenco and Neltume. A visual clinical examination was performed to determine the number of individual malocclusions according to the method of Björk et al. (1964). For data analysis descriptive statistic was performed using Excel program. Prevalence of malocclusions was 60 percent at 6 years and 91.3 percent at 12 years. Prevalence data exceed those reported nationwide so it is necessary to reinforce promotional measures in the population and promote preventive - interceptive actions taking place in these locations.

Relationship between chronic complications, hypertension, and health-related quality of life in Portuguese patients with type 2 diabetes.

BACKGROUND: The aim of this study was to assess the relationship between health-related quality of life (HRQoL) and the presence or absence of hypertension and diabetes-related chronic complications in type 2 diabetes, and also the association between HRQoL and the number of chronic complications. METHODS: One hundred patients with type 2 diabetes were interviewed. HRQoL was evaluated using the age-adjusted Short-Form 36 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health). RESULTS: The mean age of the study population was 62.7±8.7 years; 54.0% were male, and 51.0% were receiving only oral hypoglycemic agents. Chronic complications were related to worse HRQoL in different dimensions: peripheral neuropathy and cardiovascular disease (all, except bodily pain), retinopathy (physical functioning, general health, vitality, and mental health), peripheral arterial disease (physical functioning, role-physical, and general health), and nephropathy (general health and vitality). Hypertension was related to worse general health and vitality. An increased number of chronic complications was associated with worse HRQoL in all dimensions of Short-Form 36 except for the bodily pain dimension. CONCLUSION: The presence and increased number of diabetes-related chronic complications, and the presence of hypertension were related to worse age-adjusted HRQoL. Peripheral neuropathy and cardiovascular disease were more strongly related to age-adjusted HRQoL.

Health-related quality of life in type 1 and type 2 diabetic patients in a Portuguese central public hospital.

BACKGROUND: Diabetes mellitus is a chronic metabolic disease, the prevalence of which has registered a considerable increase, mainly in adults and elderly. The purpose of this study was to assess the relationship between health-related quality of life in patients with diabetes and sex, body mass index, type of diabetes and treatment regimens (type 1 diabetes: intensive versus conventional treatment; type 2 diabetes: insulin use versus non-insulin use), and duration of diabetes. METHODS: One hundred and twenty-four patients with diabetes were interviewed. Health-related quality of life was evaluated using the age-adjusted Short-Form 36 dimensions (physical functioning, role-physical, bodily pain, general health, vitality, social functioning, role-emotional, and mental health), and related to demographic and clinical variables. Independent samples t-tests and One-Way Analysis of Variance were used to compare means of independent samples. The degree of association between pairs of variables was measured by Pearson's (r) or Spearman's (rs ) correlation coefficients. RESULTS: The mean age of the study population was 55.7±16.4 years; 54.8% were male, and 77.4% had type 2 diabetes. Females reported worse quality of life than males in all dimensions of the Short-Form 36, except for role-physical and bodily pain. Obese patients had worse physical functioning than normal weight and overweight patients, and worse vitality than their normal weight counterparts. Type 2 diabetic patients taking insulin had lower physical functioning and vitality than those without insulin therapy. Longer duration of diabetes was associated with lower physical functioning, role-physical, general health, vitality, role-emotional, and mental health. CONCLUSION: Being female, obese, having type 2 diabetes and taking insulin, and having a longer disease duration are characteristics associated with worse age-adjusted quality of life in patients with diabetes.

Bayesian estimation for optimized structured illumination microscopy.

Structured illumination microscopy is a recent imaging technique that aims at going beyond the classical optical resolution by reconstructing high-resolution (HR) images from low-resolution (LR) images acquired through modulation of the transfer function of the microscope. The classical implementation has a number of drawbacks, such as requiring a large number of images to be acquired and parameters to be manually set in an ad-hoc manner that have, until now, hampered its wide dissemination. Here, we present a new framework based on a Bayesian inverse problem formulation approach that enables the computation of one HR image from a reduced number of LR images and has no specific constraints on the modulation. Moreover, it permits to automatically estimate the optimal reconstruction hyperparameters and to compute an uncertainty bound on the estimated values. We demonstrate through numerical evaluations on simulated data and examples on real microscopy data that our approach represents a decisive advance for a wider use of HR microscopy through structured illumination.

Detection of Trypanosoma cruzi in untreated chronic chagasic patients is improved by using three parasitological methods simultaneously.

OBJECTIVES: This study compared three parasitological methods applied simultaneously in individuals with untreated chronic Chagas' disease in order to determine their individual and combined performances. METHODS: From a total of 100 chronic chagasic patients from endemic areas of Chile, with informed consent, we extracted 2 mL of peripheral venous blood for PCR (PCR-B) and applied two xenodiagnosis (XD) boxes with seven uninfected Triatoma infestans nymphs each for microscopic examination and PCR of faecal samples of the triatomines fed on each patient (PCR-XD). The PCR-B and PCR-XD reactions were performed with oligonucleotides 121 and 122, which anneal to the four constant regions of the minicircles of Trypanosoma cruzi kinetoplasts. The 330 bp PCR product was analysed by electrophoresis in a 2% agarose gel and visualized by staining with ethidium bromide. RESULTS: PCR-B detected T. cruzi in 58% of the cases, while PCR-XD proved to be more sensitive than XD (67% versus 14%, respectively) (P = 0.0001). There was no difference between the detection power of PCR-B and PCR-XD (P = 0.222). The percentage detected as positive was much greater when the three tests were considered (84%) (P = 0.00001). CONCLUSIONS: The simultaneous application of more than one technique for the parasitological diagnosis of Chagas' disease in untreated individuals increases the possibility of detection of T. cruzi.

Axial coding in full-field microscopy using three-dimensional structured illumination implemented with no moving parts.

We report a simple optical setup to produce both axial and lateral structured illumination through a single objective lens. With a minimum of six full-field images obtained without moving either the sample or the microscope objective, 100 nm diameter fluorescent beads can be localized axially with an accuracy of 50 nm in a 1.76-microm-thick layer. We show that this axial localization improvement can easily be combined with classical lateral structured illumination, so that lateral resolution enhancement by a factor of 2 is maintained.

Tumores fetales: II parte / Fetal tumors: part II

Se presenta la segunda parte de una revisión resumida de los diferentes tumores fetales, haciendo énfasis en su diagnóstico prenatal y posibles tratamientos intrauterinos. En esta segunda parte se analizan los tumores torácicos, abdominales y misceláneos.