Evaluación de los efectos de un dispositivo de entrenamiento de los músculos inspiratorios sobre la oxigenación muscular y la activación neuromuscular de los músculos respiratorios / [Evaluation of the effects of an inspiratory muscle training device on muscle oxygenation and neuromuscular activation of the respiratory muscles]

Objetivo: Comparar los cambios en la actividad electromiográfica y oxigenación muscular periférica de los músculos intercostales, en su condición de musculatura accesoria a la respiración, en pacientes con EPOC durante la realización de un test de marcha de 6 minutos (TM6M) con y sin el uso de un dispositivo FeelBreathe (FB).Material y métodos: Se seleccionaron a 20 sujetos diagnosticados de EPOC a los que se les realizaron dos TM6M separados al menos por 60 minutos. Aleatoriamente, cada uno de los pacientes realizó dos TM6M, uno usando el dispositivo FB y el otro sin FB (SFB) y se midieron durante la realización de ambos TM6M la actividad electromiográfica (EMG) obteniéndose la raíz de la media cuadrática (RMS), y por otro lado la oxigenación tisular de los músculos intercostales a través de la variable de oxihemoglobina (HbO2).Resultados: No hubo diferencias significativas en la distancia recorrida en ambos TM6M con FC a SFB. Tanto la RMS como la oxigenación tisular mostraron valores similares entre la condición FB vs. SFB al final de ambas pruebas (32,26 ± 101,94 μV vs 28,25 ± 87,02 μV; p = 0,16 y 70,63 ± 18,80 vs 70,74 ± 16,77; p = 0,975 respectivamente).Conclusiones: El estímulo de trabajo de la musculatura intercostal durante el TM6M con el dispositivo FB no compromete la aparición de la fatiga temprana por un exceso de activación o disminución de la oxigenación de dichos músculos al nivel de intensidad del TM6M. (AU)

Objective: To compare changes in electromyographic activity and peripheral muscle oxygenation of the intercostal muscles, in their condition as accessory muscles for respiration, in patients with COPD during a 6-minute walk test (6MWT) with and without the use of a FeelBreathe (FB) device.Material and methods: 20 subjects diagnosed with COPD who underwent two 6MTMs separated by at least 60 minutes were selected. Randomly, each of the patients underwent two 6MWT, one using the FB device and the other without FB (SFB) and electromyographic activity (EMG) was measured during the performance of both 6MWT, obtaining the root mean square (RMS), and on the other hand, tissue oxygenation of the intercostal muscles through the oxyhemoglobin (HbO2) variable.Results: There were no significant differences in the distance traveled in both 6MWT with HR to SFB. Both RMS and tissue oxygenation showed similar values between the FB condition vs. SFB at the end of both tests (32.26 ± 101.94 μV vs 28.25 ± 87.02 μV; p = 0.16 and 70.63 ± 18.80 vs 70.74 ± 16.77; p = 0.975 respectively).Conclusions: The work stimulus of the intercostal muscles during the 6MWT with the FB device does not compromise the appearance of early fatigue due to excessive activation or decreased oxygenation of these muscles at the intensity level of the 6MWT. (AU)

Sodium-glucose cotransporter 2 (SGLT-2) inhibitors and microvascular outcomes in patients with type 2 diabetes: systematic review and meta-analysis.

PURPOSE: The effect of the sodium-glucose 2 (SGLT-2) inhibitors on microvascular complications remains uncertain. We performed a systematic review to determine the efficacy of the SGLT-2 inhibitors on microvascular outcomes in patients with type 2 diabetes. METHODS: A comprehensive search was performed using Ovid, MEDLINE, EMBASE, Web of Science, and Scopus from inception to May 2019. Randomized trials comparing SGLT-2 inhibitors with placebo or other medication for type 2 diabetes for ≥ 4 weeks were included. Diabetes-related microvascular complications such as nephropathy, retinopathy, neuropathy, and peripheral vascular disease were evaluated. A random-effect model using mean differences for continuous outcomes and risk ratio for dichotomous outcomes was used to synthesize data. PROSPERO (CRD 42017076460). RESULTS: A total of 40 RCTs with overall moderate quality of evidence were included. SGLT-2 inhibitors reduced the risk of renal-replacement therapy (0.65; 95% CI 0.54-0.79), renal death (0.57; 95% CI 0.49-0.65), and progression of albuminuria (0.69; 95% CI 0.66-0.73). Conversely, they appeared ineffective in maintaining eGFR (0.33; 95% CI - 0.74 to 1.41) or reducing serum creatinine (- 0.07; 95% CI - 0.26 to 0.11), whereas urine albumin-creatinine ratio (- 23.4; 95% CI - 44.6 to - 2.2) was reduced. Risk of amputation was non-significant (1.30; 95% CI 0.93-1.83). No available data were found regarding neuropathy and retinopathy to perform a quantitative analysis. CONCLUSION: SGLT-2 inhibitors may reduce the risk of renal patient-important outcomes but fail to improve surrogate outcomes. Apparently, no increased risk of amputations was observed with these medications. No data were available regarding other microvascular complications.

Sun Protection Habits and Sunburn in Elite Aquatics Athletes: Surfers, Windsurfers and Olympic Sailors.

The objective of this study was to analyse the sun exposure habits of elite aquatics athletes, together with their sunburn history and skin examination habits, taking into account differences by sex and between sports. A cross-sectional health survey was conducted at world championship events during which elite surfers, windsurfers and Olympic sailors from 30 different countries were invited to participate. The athletes were asked to complete a self-administered questionnaire focused on sun protection habits, sun exposure and sports practices. The survey was completed by 240 athletes, 171 men (71.3%) and 69 women (28.8%), with a mean age of 22 years (SD 5.86) and skin phototypes I (6.3%), II (3.3%), III (22.0%), IV (32.5%), V (9.2%) and VI (1.7%). There were significant differences between male and female athletes in skin self-examination (p < 0.001) and in the use of sunglasses (p < 0.001). In sunburn history during the last season, there were significant differences (p < 0.001) among the three sports analysed, in both sexes. The mean rate of sunburn during the previous season was 76.7%, and 27.5% of participants reported having experienced three or more sunburns that lasted at least 1 day. This type of athlete is at high risk of sunburn and hence of future skin cancer. However, there is a general lack of awareness of this risk. This study highlights the need to inform such athletes and to raise awareness of the dangers, through educational interventions on the importance of protecting against sunburn in order to reduce the future incidence of skin cancer.

Efficacy and safety of triple therapy with dapagliflozin add-on to saxagliptin plus metformin over 52 weeks in patients with type 2 diabetes.

We previously reported that dapagliflozin versus placebo as add-on to saxagliptin plus metformin resulted in greater reductions in glycated haemoglobin (A1C), fasting plasma glucose (FPG) and body weight (BW) after 24 weeks of treatment in patients with type 2 diabetes (T2D). Here we report results after 52 weeks of treatment. Patients stabilized on open-label metformin and saxagliptin 5 mg/day for 8-16 weeks were randomized to placebo or dapagliflozin 10 mg/day plus open-label saxagliptin plus metformin for 52 weeks. Changes from baseline to week 52 were greater with dapagliflozin versus placebo in A1C (-0.74% vs. 0.07%), FPG (-27 vs. 10 mg/dL) and BW (-2.1 vs. -0.4 kg). More patients achieved A1C <7% with dapagliflozin (29.4%) versus placebo (12.6%). Adverse events were similar with dapagliflozin (66%) and placebo (71%), and hypoglycaemia was rare (≤2%). Genital infections occurred more often with dapagliflozin (6%) than with placebo (1%); frequency of urinary tract infections was similar between the two groups (9% vs. 10%). Triple therapy with dapagliflozin add-on to saxagliptin plus metformin is a durable, effective and well-tolerated intervention for the treatment of T2D.

Usefulness of direct fluorescent in buffy coat in the diagnosis of Candida sepsis in neonates.

OBJECTIVE: The objective of this study is to assess the clinical utility of direct fluorescent assay in buffy coat in the diagnosis of Candida sepsis (CS) in neonates. STUDY DESIGN: A cross-sectional study was conducted in a Neonatal Intensive Care Unit and 22 neonates with suspected CS were enrolled. Fungus isolation from blood cultures and direct fluorescent tests in buffy coat were performed and validity parameters were estimated. RESULTS: Candida was isolated in 13/22 (59%) blood cultures. The direct fluorescent test was positive in 12/13 and 1/9 cases with positive and negative blood culture as corresponding. Estimated sensitivity, specificity, positive predictive value, negative predictive value, positive likehood ratio and negative likehood ratio were 92%, 89%, 92%, 89%, 8.31 and 0.09, respectively. CONCLUSION: The direct fluorescent assay in buffy coat might be useful to support early and accurate diagnosis of CS in neonates.

Androgen receptor gene polymorphism influence fat accumulation: A longitudinal study from adolescence to adult age.

To determine the influence of androgen receptor CAG and GGN repeat polymorphisms on fat mass and maximal fat oxidation (MFO), CAG and GGN repeat lengths were measured in 128 young boys, from which longitudinal data were obtained in 45 of them [mean ± SD: 12.8 ± 3.6 years old at recruitment, and 27.0 ± 4.8 years old at adult age]. Subjects were grouped as CAG short (CAGS ) if harboring repeat lengths ≤ 21, the rest as CAG long (CAGL ); and GGN short (GGNS ) if GGN repeat lengths ≤ 23, or long if > 23 (GGNL ). CAGS and GGNS were associated with lower adiposity than CAGL or GGNL (P < 0.05). There was an association between the logarithm of CAG repeats polymorphism and the changes of body mass (r = 0.34, P = 0.03). At adult age, CAGS men showed lower accumulation of total body and trunk fat mass, and lower resting metabolic rate (RMR) and MFO per kg of total lean mass compared with CAGL (P < 0.05). GGNS men also showed lower percentage of body fat (P < 0.05). In summary, androgen receptor CAG and GGN repeat polymorphisms are associated with RMR, MFO, fat mass, and its regional distribution in healthy male adolescents, influencing fat accumulation from adolescence to adult age.

A time-efficient reduction of fat mass in 4 days with exercise and caloric restriction.

To determine whether a fast reduction in fat mass can be achieved in 4 days by combining caloric restriction (CR: 3.2 kcal/kg body weight per day) with exercise (8-h walking + 45-min arm cranking per day) to induce an energy deficit of ∼5000 kcal/day, 15 overweight men underwent five experimental phases: pretest, exercise + CR for 4 days (WCR), control diet + reduced exercise for 3 days (DIET), and follow-up 4 weeks (POST1) and 1 year later (POST2). During WCR, the diet consisted solely of whey protein (n = 8) or sucrose (n = 7) (0.8 g/kg body weight per day). After WCR, DIET, POST1, and POST2, fat mass was reduced by a mean of 2.1, 2.8, 3.8, and 1.9 kg (P < 0.05), with two thirds of this loss from the trunk; and lean mass by 2.8, 1.0, 0.5, and 0.4 kg, respectively. After WCR, serum glucose, insulin, homeostatic model assessment, total and low-density lipoprotein cholesterol and triglycerides were reduced, and free fatty acid and cortisol increased. Serum leptin was reduced by 64%, 50%, and 33% following WCR, DIET, and POST1, respectively (P < 0.05). The effects were similar in both groups. In conclusion, a clinically relevant reduction in fat mass can be achieved in overweight men in just 4 days by combining prolonged exercise with CR.

EBV, HCMV, HHV6, and HHV7 screening in bone marrow samples from children with acute lymphoblastic leukemia.

Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood worldwide and Mexico has reported one of the highest incidence rates. An infectious etiology has been suggested and supported by epidemiological evidences; however, the identity of the involved agent(s) is not known. We considered that early transmitted lymphotropic herpes viruses were good candidates, since transforming mechanisms have been described for them and some are already associated with human cancers. In this study we interrogated the direct role of EBV, HCMV, HHV6, and HHV7 human herpes viruses in childhood ALL. Viral genomes were screened in 70 bone marrow samples from ALL patients through standard and a more sensitive nested PCR. Positive samples were detected only by nested PCR indicating a low level of infection. Our result argues that viral genomes were not present in all leukemic cells, and, hence, infection most likely was not part of the initial genetic lesions leading to ALL. The high statistical power of the study suggested that these agents are not involved in the genesis of ALL in Mexican children. Additional analysis showed that detected infections or coinfections were not associated with prognosis.

Note: Limitations of the optoelectronic control for carbon nanoparticles synthesis via arc-discharge in solution.

Submerged electric arc discharge in liquids has shown to be a promising method for synthesizing a wide variety of nanomaterials. However, it requires an accurate current stability control to ensure the desired purity and structure of the products. The discharge stability control through light emission has been previously studied, but still requires further investigation to clarify the influence of some parameters. The present work has studied the solution's transmittance variation over time, the correlation between the arc light emission and the arc current, and the feasibility of controlling the arc current by using a specific wavelength of the arc light spectrum. Several limitations of the optoelectronic control were found at low currents (I < 50 A).

A reliable unipedal stance test for the assessment of balance using a force platform.

BACKGROUND: The aim was to develop a unipedal stance test for the assessment of balance using a force platform. METHODS: A single-leg balance test was conducted in 23 students (mean ± SD) age: 23 ± 3 years) in a standard position limiting the movement of the arms and non-supporting leg. Six attempts, with both the jumping (JL) and the contralateral leg (CL), were performed under 3 conditions: 1) eyes opened; 2) eyes closed; 3) eyes opened and executing a precision task. The same protocol was repeated two-week apart. RESULTS: The mean and the best result of the six attempts performed each day were taken as representative of balance. The speed of the centre of pressure (CP-Speed) showed excellent reliability for the "best result" analysis in all tests (ICCs 0.87-0.97), except in the test with the eyes closed performed on the CL (ICC<0.4). The CP-Speed had better reliability with the "best result" than with the "mean result" analysis (P<0.05), whilst no significant differences were observed between the JL and the CL (P=0.71 and P=0.96 for mean and best results analysis, respectively). A lower dispersion in the Bland and Altman graph was observed with the eyes opened than closed, and the dynamic test. CONCLUSION: The single-leg stance balance test proposed is a reliable method to assess balance, especially when performed in a static position, with the eyes opened and using the best result of six attempts as reference, independently of the stance leg.

Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia.

BACKGROUND: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). METHODS: A case-control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. RESULTS: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47-11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20-0.91). CONCLUSION: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS.

Isoinertial and isokinetic sprints: muscle signalling.

To determine if the muscle signalling response to a 30 s all-out sprint exercise is modulated by the exercise mode and the endocrine response, 27 healthy volunteers were divided in 2 groups that performed isokinetic (10 men and 5 women) and isoinertial (7 men and 5 women) Wingate tests. Blood samples and vastus lateralis muscle biopsies were taken before, immediately after, 30 and 120 min after the sprints. Groups were comparable in age, height, body weight, percentage of body fat, peak power per kg of lower extremities lean mass (Pmax) and muscle fibre types. However, the isoinertial group achieved a 25% greater mean power (Pmean). Sprint exercise elicited marked increases in the musculus vastus lateralis AMPKα, ACCß, STAT3, STAT5 and ERK1/2 phosphorylation (all P<0.05). The AMPKα, STAT3, and ERK1/2 phosphorylation responses were more marked after the isoinertial than isokinetic test (interaction: P<0.01). The differences in muscle signalling could not be accounted for by differences in Pmax, although Pmean could explain part of the difference in AMPKα phosphorylation. The leptin, insulin, glucose, GH, IL-6, and lactate response were similar in both groups. In conclusion, the muscle signalling response to sprint exercise differs between isoinertial and isokinetic sprints.

Normal mitochondrial function and increased fat oxidation capacity in leg and arm muscles in obese humans.

AIM/HYPOTHESIS: The aim of this study was to investigate mitochondrial function, fibre-type distribution and substrate oxidation during exercise in arm and leg muscles in male postobese (PO), obese (O) and age- and body mass index (BMI)-matched control (C) subjects. The hypothesis of the study was that fat oxidation during exercise might be differentially preserved in leg and arm muscles after weight loss. METHODS: Indirect calorimetry was used to calculate fat and carbohydrate oxidation during both progressive arm-cranking and leg-cycling exercises. Muscle biopsy samples were obtained from musculus deltoideus (m. deltoideus) and m. vastus lateralis muscles. Fibre-type composition, enzyme activity and O(2) flux capacity of saponin-permeabilized muscle fibres were measured, the latter by high-resolution respirometry. RESULTS: During the graded exercise tests, peak fat oxidation during leg cycling and the relative workload at which it occurred (FatMax) were higher in PO and O than in C. During arm cranking, peak fat oxidation was higher in O than in C, and FatMax was higher in O than in PO and C. Similar fibre-type composition was found between groups. Plasma adiponectin was higher in PO than in C and O, and plasma leptin was higher in O than in PO and C. CONCLUSIONS: In O subjects, maximal fat oxidation during exercise and the eliciting relative exercise intensity are increased. This is associated with higher intramuscular triglyceride levels and higher resting non esterified fatty acid (NEFA) concentrations, but not with differences in fibre-type composition, mitochondrial function or muscle enzyme levels compared with Cs. In PO subjects, the changes in fat oxidation are preserved during leg, but not during arm, exercise.

Extended endoscopic endonasal approach to the skull base.

OBJECTIVE: Different approaches to the skull base have been developed through the sphenoidal sinus. Traditional boundaries of the trans-sphenoidal approach can be extended in antero-posterior and lateral planes. We review our experience with the extended endoscopic endonasal approach in the first 12 cases. METHODS: We used the extended endoscopic endonasal approach in 12 patients with different lesions of the skull base. This study specifically focuses on the type of lesions, surgical approach, outcome and surgical complications. RESULTS: The extended endoscopic endonasal approach was used in 12 patients with the following lesions: 4 invasive adenomas to the cavernous sinus, 2 clival chordomas, 2 craniopharyngiomas, 1 hypothalamic astrocytoma and 3 pituitary adenomas extended upon the tuberculum. Gross total resection was achieved in 8 cases (66.7%) subtotal resection in 3 and just a biopsy could be accomplished in the case of astrocytoma. This last patient developed meningo-encephalitis and died two weeks later. CONCLUSIONS: The extended endoscopic endonasal approach is a promising minimally invasive alternative for selected cases with sellar, parasellar or clivus lesions. As techniques and technology advance, this approach may become the procedure of choice for most lesions and should be considered an option in the management of the patients with these complex pathologies by skull base surgeons.

Day-surgery laparoscopic cholecystectomy: factors influencing same-day discharge.

BACKGROUND: Day-surgery laparoscopic cholecystectomy (LC) should be the procedure of choice in patients with symptomatic gallstone disease. This article assesses feasibility, patient outcome and predictive factors for successful day-case laparoscopic cholecystectomy. METHOD: A retrospective analysis of our prospective database of 176 patients following laparoscopic cholecystectomy in a day-surgery unit was performed. A telephone interview was conducted within 24 h after discharge and again after 3 weeks. RESULTS: Of the 176 cases included in this study, 74% had biliary colic, cholecystitis (16%), pancreatitis (8%), and jaundice (2%). In addition to LC, nine patients (5.1%) underwent laparoscopic bile duct exploration and ten (5.7%) had an additional procedure performed. Eighty-six percent of the patients were discharged the same day. Multivariate analysis identified risk factors affecting same-day discharge, including age greater than 50 years and intraoperative complications. Bile duct exploration reduced the odds of discharge but did not reach significance. Postoperative telephone interviews identified high patient satisfaction with 86% of respondents recommending LC as a day-surgery procedure. CONCLUSION: Day-surgery LC is a safe procedure with an acceptable rate of patient discharge. However, intraoperative complications or age over 50 years adversely affected the same-day discharge rate and as such should be taken into consideration when planning day-case laparoscopic cholecystectomy.

The segmentation clock in mice: interaction between the Wnt and Notch signalling pathways.

In the last few years, the efforts to elucidate the mechanisms underlying the segmentation clock in various vertebrate species have multiplied. Early evidence suggested that oscillations are caused by one of the genes under the Notch signalling pathway (like those of the her or Hes families). Recently, Aulehla et al. [Wnt3a plays a major role in the segmentation clock controlling somitogenesis. Dev. Cell 4, 395-406] discovered that Axin2 (a gene under the Wnt3a signalling pathway) also oscillates in the presomitic mesoderm (PSM) of mice embryos and proposed some mechanisms through which the Notch and Wnt3a pathways may interact. They further suggested that a decreasing concentration of Wnt3a along the PSM may be the gradient the segmentation clock interacts with to form somites. These results were reviewed by Rida et al. [A notch feeling of somite segmentation and beyond. Dev. Biol. 265, 2-22], who introduced a complex clockwork comprising genes Hes1, Lfng (under the Notch pathway), and Axin2, as well as their multiple interactions. In the present work we develop a mathematical model based on the Rida et al. review and use it to tackle some of the questions raided by the Aulehla et al. paper: can the Axin2 feedback loop constitute a clock? Could a decreasing Wnt3a signaling constitute the wavefront, where phase is recorded and the spatial pattern laid down? What is the master oscillator?

Second eye of patients with unilateral neovascular age-related macular degeneration: Caucasians vs Chinese.

PURPOSE: To investigate the correlation between morphological features of choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) in the first eye and the severity of age-related maculopathy (ARM) in the fellow eyes in two racial groups: Caucasians and Chinese. PARTICIPANTS: A total of 135, fluorescein angiograms of patients with unilateral neovascular AMD and ARM in the fellow eyes were included in the study: 38 Caucasians from King's College Hospital, UK; 45 Caucasians from West Kent Eye Centre, UK; 52 Chinese from Hong Kong Eye Hospital, Hong Kong. MAIN OUTCOME MEASURES: CNV subtype in the affected eye and ARM severity in the second eyes. RESULTS: Although the proportion of CNV subtypes in the three groups were similar, the Chinese cohort showed significantly less ARM severity compared to the Caucasian cohorts (P < 0.05). CONCLUSION: Although drusen and retinal pigmentary changes may be prognostic indicators of CNV, this study suggest that other factors contribute significantly to the pathogenesis of CNV in AMD.

Feasibility and morbidity of reversal of Hartmann's.

OBJECTIVE: Reversal of Hartmann's is a major surgical procedure and associated with substantial morbidity and mortality. METHOD: This study retrospectively analysed the data at a single centre over an eight-year period to assess the clinical results and morbidity of reversal of Hartmann's. RESULTS: One hundred and ten Hartmann's procedures were performed during the period. Only 66 (61%) of patients had a reversal. Advanced age and comorbidity were the primary reasons for not reversing. Complications among the 66 patients (36 males and 30 females) who underwent reversal occurred in 26 (41%). There were no deaths. Patients who underwent reversal were ASA 2 (60%), ASA 3 (25%) and ASA 4 (4.6%). Univariate analysis demonstrated a significant association between complications following reversal and ASA grade (P =0.01), and hypertension (P = 0.03) There was no correlation between the patient variables and anastomotic leakage. Multiple logistic regression analysis showed a significant influence of hypertension, smoking and ASA grade on complications. CONCLUSIONS: About 40% of patients who undergo Hartmann's procedure will not have a reversal. Reversal is a feasible operation for selected patients, but there is a high complication rate.