Early-life external exposome in children 2-5 years old in Colombia.

Exposome studies are advancing in high-income countries to understand how multiple environmental exposures impact health. However, there is a significant research gap in low- and middle-income and tropical countries. We aimed to describe the spatiotemporal variation of the external exposome, its correlation structure between and within exposure groups, and its dimensionality. A one-year follow-up cohort study of 506 children under 5 in two cities in Colombia was conducted to evaluate asthma, acute respiratory infections, and DNA damage. We examined 48 environmental exposures during pregnancy and 168 during childhood in eight exposure groups, including atmospheric pollutants, natural spaces, meteorology, built environment, traffic, indoor exposure, and socioeconomic capital. The exposome was estimated using geographic information systems, remote sensing, spatiotemporal modeling, and questionnaires. The median age of children at study entry was 3.7 years (interquartile range: 2.9-4.3). Air pollution and natural spaces exposure decreased from pregnancy to childhood, while socioeconomic capital increased. The highest median correlations within exposure groups were observed in meteorology (r = 0.85), traffic (r = 0.83), and atmospheric pollutants (r = 0.64). Important correlations between variables from different exposure groups were found, such as atmospheric pollutants and meteorology (r = 0.76), natural spaces (r = -0.34), and the built environment (r = 0.53). Twenty principal components explained 70%, and 57 explained 95% of the total variance in the childhood exposome. Our findings show that there is an important spatiotemporal variation in the exposome of children under 5. This is the first characterization of the external exposome in urban areas of Latin America and highlights its complexity, but also the need to better characterize and understand the exposome in order to optimize its analysis and applications in local interventions aimed at improving the health conditions and well-being of the child population and contributing to environmental health decision-making.

Trans-Spinal Direct Current Stimulation in Neurological Disorders: A systematic review.

BACKGROUND AND PURPOSE: Trans-spinal direct current stimulation (tsDCS) is a noninvasive stimulation technique that applies direct current stimulation over spinal levels. However, the effectiveness and feasibility of this stimulation are still unclear. This systematic review summarizes the effectiveness of tsDCS in clinical and neurophysiological outcomes in neurological patients, as well as its feasibility and safety. METHODS: The search was conducted using the following databases: PEDro, Scopus, Web of Science, CINAHL, SPORTDiscus, and PubMed. The inclusion criteria were: Participants : people with central nervous system diseases; Interventions : tsDCS alone or in combination with locomotion training; Comparators : sham tsDCS, transcranial direct current stimulation, or locomotion training; Outcomes : clinical and neurophysiological measures; and Studies : randomized clinical trials. RESULTS: Eight studies with a total of 143 subjects were included. Anodal tsDCS led to a reduction in hypertonia, neuropathic pain intensity, and balance deficits in people with hereditary spastic paraplegia, multiple sclerosis, and primary orthostatic tremor, respectively. In contrast, cathodal tsDCS only had positive effects on balance and tremor in people with primary orthostatic tremor. No severe adverse effects were reported during and after anodal or cathodal tsDCS. DISCUSSION AND CONCLUSIONS: Although certain studies have found an effect of anodal tsDCS on specific clinical outcomes in people with central nervous system diseases, its effectiveness cannot be established since these findings have not been replicated and the results were heterogeneous. This stimulation was feasible and safe to apply. Further studies are needed to replicate the obtained results of tsDCS when applied in populations with neurological diseases.

Characterization of Magnetoresistive Shunts and Its Sensitivity Temperature Compensation.

The main purpose of the paper is to show how a magnetoresistive (MR) element can work as a current sensor instead of using a Wheatstone bridge composed by four MR elements, defining the concept of a magnetoresistive shunt (MR-shunt). This concept is reached by considering that once the MR element is biased at a constant current, the voltage drop between its terminals offers information, by the MR effect, of the current to be measured, as happens in a conventional shunt resistor. However, an MR-shunt has the advantage of being a non-dissipative shunt since the current of interest does not circulate through the material, preventing its self-heating. Moreover, it provides galvanic isolation. First, we propose an electronic circuitry enabling the utilization of the available MR sensors integrated into a Wheatstone bridge as sensing elements (MR-shunt). This circuitry allows independent characterization of each of the four elements of the bridge. An independently implemented MR element is also analyzed. Secondly, we propose an electronic conditioning circuit for the MR-shunt, which allows both the bridge-integrated element and the single element to function as current sensors in a similar way to the sensing bridge. Third, the thermal variation in the sensitivity of the MR-shunt, and its temperature coefficient, are obtained. An electronic interface is proposed and analyzed for thermal drift compensation of the MR-shunt current sensitivity. With this hardware compensation, temperature coefficients are experimentally reduced from 0.348%/°C without compensation to -0.008%/°C with compensation for an element integrated in a sensor bridge and from 0.474%/°C to -0.0007%/°C for the single element.

Analysis of Breast Cancer Mortality in the US-1975 to 2019.

Importance: Breast cancer mortality in the US declined between 1975 and 2019. The association of changes in metastatic breast cancer treatment with improved breast cancer mortality is unclear. Objective: To simulate the relative associations of breast cancer screening, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer with improved breast cancer mortality. Design, Setting, and Participants: Using aggregated observational and clinical trial data on the dissemination and effects of screening and treatment, 4 Cancer Intervention and Surveillance Modeling Network (CISNET) models simulated US breast cancer mortality rates. Death due to breast cancer, overall and by estrogen receptor and ERBB2 (formerly HER2) status, among women aged 30 to 79 years in the US from 1975 to 2019 was simulated. Exposures: Screening mammography, treatment of stage I to III breast cancer, and treatment of metastatic breast cancer. Main Outcomes and Measures: Model-estimated age-adjusted breast cancer mortality rate associated with screening, stage I to III treatment, and metastatic treatment relative to the absence of these exposures was assessed, as was model-estimated median survival after breast cancer metastatic recurrence. Results: The breast cancer mortality rate in the US (age adjusted) was 48/100 000 women in 1975 and 27/100 000 women in 2019. In 2019, the combination of screening, stage I to III treatment, and metastatic treatment was associated with a 58% reduction (model range, 55%-61%) in breast cancer mortality. Of this reduction, 29% (model range, 19%-33%) was associated with treatment of metastatic breast cancer, 47% (model range, 35%-60%) with treatment of stage I to III breast cancer, and 25% (model range, 21%-33%) with mammography screening. Based on simulations, the greatest change in survival after metastatic recurrence occurred between 2000 and 2019, from 1.9 years (model range, 1.0-2.7 years) to 3.2 years (model range, 2.0-4.9 years). Median survival for estrogen receptor (ER)-positive/ERBB2-positive breast cancer improved by 2.5 years (model range, 2.0-3.4 years), whereas median survival for ER-/ERBB2- breast cancer improved by 0.5 years (model range, 0.3-0.8 years). Conclusions and Relevance: According to 4 simulation models, breast cancer screening and treatment in 2019 were associated with a 58% reduction in US breast cancer mortality compared with interventions in 1975. Simulations suggested that treatment for stage I to III breast cancer was associated with approximately 47% of the mortality reduction, whereas treatment for metastatic breast cancer was associated with 29% of the reduction and screening with 25% of the reduction.

Collaborative Modeling to Compare Different Breast Cancer Screening Strategies: A Decision Analysis for the US Preventive Services Task Force.

Importance: The effects of breast cancer incidence changes and advances in screening and treatment on outcomes of different screening strategies are not well known. Objective: To estimate outcomes of various mammography screening strategies. Design, Setting, and Population: Comparison of outcomes using 6 Cancer Intervention and Surveillance Modeling Network (CISNET) models and national data on breast cancer incidence, mammography performance, treatment effects, and other-cause mortality in US women without previous cancer diagnoses. Exposures: Thirty-six screening strategies with varying start ages (40, 45, 50 years) and stop ages (74, 79 years) with digital mammography or digital breast tomosynthesis (DBT) annually, biennially, or a combination of intervals. Strategies were evaluated for all women and for Black women, assuming 100% screening adherence and "real-world" treatment. Main Outcomes and Measures: Estimated lifetime benefits (breast cancer deaths averted, percent reduction in breast cancer mortality, life-years gained), harms (false-positive recalls, benign biopsies, overdiagnosis), and number of mammograms per 1000 women. Results: Biennial screening with DBT starting at age 40, 45, or 50 years until age 74 years averted a median of 8.2, 7.5, or 6.7 breast cancer deaths per 1000 women screened, respectively, vs no screening. Biennial DBT screening at age 40 to 74 years (vs no screening) was associated with a 30.0% breast cancer mortality reduction, 1376 false-positive recalls, and 14 overdiagnosed cases per 1000 women screened. Digital mammography screening benefits were similar to those for DBT but had more false-positive recalls. Annual screening increased benefits but resulted in more false-positive recalls and overdiagnosed cases. Benefit-to-harm ratios of continuing screening until age 79 years were similar or superior to stopping at age 74. In all strategies, women with higher-than-average breast cancer risk, higher breast density, and lower comorbidity level experienced greater screening benefits than other groups. Annual screening of Black women from age 40 to 49 years with biennial screening thereafter reduced breast cancer mortality disparities while maintaining similar benefit-to-harm trade-offs as for all women. Conclusions: This modeling analysis suggests that biennial mammography screening starting at age 40 years reduces breast cancer mortality and increases life-years gained per mammogram. More intensive screening for women with greater risk of breast cancer diagnosis or death can maintain similar benefit-to-harm trade-offs and reduce mortality disparities.

Effectiveness of transcranial direct current stimulation on balance and gait in patients with multiple sclerosis: systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Motor impairments are very common in neurological diseases such as multiple sclerosis. Noninvasive brain stimulation could influence the motor function of patients. OBJECTIVE: The aim of this meta-analysis was to evaluate the effectiveness of transcranial direct current stimulation (tDCS) on balance and gait ability in patients with multiple sclerosis. Additionally, a secondary aim was to compare the influence of the stimulation location of tDCS on current effectiveness. METHODS: A search was conducted for randomized controlled trials published up to May 2023 comparing the application of tDCS versus a sham or control group. The primary outcome variables were balance and gait ability. RESULTS: Eleven studies were included in the qualitative analysis, and ten were included in the quantitative analysis, which included 230 patients with multiple sclerosis. The average effect of tDCS on gait functionality was superior to that of the control group (SMD = -0.71; 95% CI, -1.05 to -0.37). However, the overall results of the tDCS vs. sham effect on static balance did not show significant differences between groups (MD = 1.26, 95% CI, -1.31 to 3.82). No significant differences were found when different locations of tDCS were compared. CONCLUSIONS: These results reveal that tDCS is an effective treatment for improving gait ability with a low quality of evidence. However, the application of tDCS has no effect on static balance in patients with multiple sclerosis with very low quality of evidence. Similarly, there seems to be no difference regarding the stimulation area with tDCS.

Natural isoquinoline alkaloids: Pharmacological features and multi-target potential for complex diseases.

Complex diseases such as neurodegenerative disorders and cancer constitute a growing public health problem due to the rising incidence and lack in effective therapies. Since pharmacotherapy based on a single target has been insufficient for drug development in complex diseases, the emerging multi-target approach is a promising strategy for the search of new drug candidates. Plant-derived isoquinoline alkaloids comprise a vast source of multimodal agents with unique structural diversity, and variated range of pharmacological activities. This review offers an exhaustive compilation of the pharmacological relevance and multi-target potential of natural isoquinolines, emphasizing their features and promising activity in complex diseases such as Alzheimer, Parkinson, and Cancer. Selected examples were discussed in depth to illustrate the most relevant structural motifs and their possible relationship with the multimodal activity offering a comprehensive baseline in the search and optimization of isoquinoline scaffolds with polypharmacological potential for complex diseases.

Percutaneous Versus Transcutaneous Electrical Nerve Stimulation for the Treatment of Musculoskeletal Pain. A Systematic Review and Meta-Analysis.

BACKGROUND: The justification for this review is the need for high-quality evidence to assist in the decision-making process when applying percutaneous electrical nerve stimulation (PENS) or transcutaneous electrical nerve stimulation (TENS) in a clinical setting. The main aim was to determine if the use of PENS is more effective and should be recommended when compared to TENS for the reduction of musculoskeletal pain intensity. METHODS: A search for randomized controlled trials (RCTs) was performed. Studies published until 31/12/2020, comparing the effectiveness of PENS and TENS, were considered. The main outcome was pain assessed with a visual analog scale or numerical pain rating scale. RESULTS: Nine RCTs were included in the qualitative analysis, with seven of them in the quantitative analysis (n = 527). The overall effect of PENS on pain was statistically but not clinically superior to TENS (mean difference [MD]=-1.0 cm; 95% confidence interval [CI]: -1.5 to -0.4) with a high level of heterogeneity (I2=76%, P > .01). When only studies with a lower risk of bias (n = 3) were analyzed, the heterogeneity decreased to I = 0% (P = .06) and no difference was observed between TENS and PENS (MD=-0.81 cm; 95% CI:-1.6 to 0.02) with a moderate recommendation level according to GRADE. There were no data concerning adverse effects. CONCLUSIONS: There is low-quality of evidence for more pain intensity reduction with PENS, but the difference was not clinically significant. However, when only studies with low risk of bias are meta-analyzed, there is a moderate quality of evidence that there is no difference when TENS or PENS is applied for pain intensity.

A New Flavanone from Chromolaena tacotana (Klatt) R. M. King and H. Rob, Promotes Apoptosis in Human Breast Cancer Cells by Downregulating Antiapoptotic Proteins.

Chromolaena tacotana is a source of flavonoids with antiproliferative properties in human breast cancer cells, the most common neoplasm diagnosed in patients worldwide. Until now, the mechanisms of cell death related to the antiproliferative activity of its flavonoids have not been elucidated. In this study, a novel flavanone (3',4'-dihydroxy-5,7-dimethoxy-flavanone) was isolated from the plant leaves and identified by nuclear magnetic resonance (NMR) and mass spectrometry (MS). This molecule selectively inhibited cell proliferation of triple-negative human breast cancer cell lines MDA-MB-231 and MCF-7 whit IC50 values of 25.3 µg/mL and 20.8 µg/mL, respectively, determined by MTT assays with a selectivity index greater than 3. Early and late pro-apoptotic characteristics were observed by annexin-V/7-AAD detection, accompanied by a high percentage of the Bcl-2 anti-apoptotic protein inactivated and the activation of effector Caspase-3 and/or 7 in breast cancer cells. It was verified the decreasing of XIAP more than Bcl-2 anti-apoptotic proteins expression, as well as the XIAP/Caspase-7 and Bcl-2/Bax complexes dissociation after flavanone treatment. Docking and molecular modeling analysis between the flavanone and the antiapoptotic protein XIAP suggests that the natural compound inhibits XIAP by binding to the BIR3 domain of XIAP. In this case, we demonstrate that the new flavanone isolated from leaves of Chomolaena tacotana has a promising and selective anti-breast cancer potential that includes the induction of intrinsic apoptosis by downregulation of the anti-apoptotic proteins XIAP and Bcl-2. New studies should deepen these findings to demonstrate its potential as an anticancer agent.

Electrical microcurrent stimulation therapy for wound healing: A meta-analysis of randomized clinical trials.

BACKGROUND: Electrical microcurrent therapy (EMT) consists of the application of low intensity (µA) currents that are similar to endogenous electric fields generated during wound healing. AIMS: To examine the effectiveness and safety of EMT for improving wound healing and pain in people with acute or chronic wounds. METHOD: Randomized clinical trials (RCTs) assessing the effectiveness of EMT in wound healing published up to August 1st, 2020 were included. The main outcomes were wound surface area, healing time, and number of wounds healed. Secondary outcomes were pain perception and adverse events. A quantitative analysis was conducted using the inverse variance and Mantel-Haenszel methods. RESULTS: Eight RCTs were included in the qualitative summary and seven in the quantitative analysis (n = 337 participants). EMT plus standard wound care (SWC) produced a greater decrease in wound surface [mean difference (MD) = -8.3 cm2; CI 95%: -10.5 to -6.0] and healing time (MD = -7.0 days; CI 95%: -11.9 to -2.1) that SWC alone, showing moderate and low certainty in the evidence, respectively. However, no differences were observed in the number of healed wounds [risk ratio = 2.0; CI 95%: 0.5 to 9.1], with very low quality of evidence. EMT decreased perceived pain (MD = -1.4; CI 95%: -2.7 to -0.2), but no differences in adverse effects were noted between groups (risk difference = 0.05; CI 95%: -0.06 to 0.17). CONCLUSIONS: EMT is an effective, safe treatment for improving wound area, healing time, and pain. Further clinical trials that include detailed intervention parameters and protocols should be designed to lower the risk of bias.

Effect of posture and body weight loading on spinal posterior root reflex responses.

The posterior root muscle response (PRM) is a monosynaptic reflex that is evoked by single pulse transcutaneous spinal cord stimulation (tSCS). The main aim of this work was to analyse how body weight loading influences PRM reflex threshold measured from several lower limb muscles in healthy participants. PRM reflex responses were evoked with 1-ms rectangular monophasic pulses applied at an interval of 6 s via a self-adhesive electrode (9 × 5 cm) at the T11-T12 vertebral level. Surface electromyographic activity of lower limb muscles was recorded during four different conditions, one in decubitus supine (DS) and the other three involving standing at 100%, 50%, and 0% body weight loading (BW). PRM threshold intensity, peak-to-peak amplitude, and latency for each muscle were analysed in different conditions study. PRM reflex threshold increased with body weight unloading compared with DS, and the largest change was observed between DS and 0% BW for the proximal muscles and between DS and 50% BW for distal muscles. Peak-to-peak amplitude analysis showed only a significant mean decrease of 34.6% (SD 10.4, p = 0.028) in TA and 53.6% (SD 15.1, p = 0.019) in GM muscles between DS and 50% BW. No significant differences were observed for PRM latency. This study has shown that sensorimotor networks can be activated with tSCS in various conditions of body weight unloading. Higher stimulus intensities are necessary to evoke reflex response during standing at 50% body weight loading. These results have practical implications for gait rehabilitation training programmes that include body weight support.

Were all trilobites fully marine? Trilobite expansion into brackish water during the early Palaeozoic.

Trilobites, key components of early Palaeozoic communities, are considered to have been invariably fully marine. Through the integration of ichnological, palaeobiological, and sedimentological datasets within a sequence-stratigraphical framework, we challenge this assumption. Here, we report uncontroversial trace and body fossil evidence of their presence in brackish-water settings. Our approach allows tracking of some trilobite groups foraying into tide-dominated estuaries. These trilobites were tolerant to salinity stress and able to make use of the ecological advantages offered by marginal-marine environments migrating up-estuary, following salt wedges either reflecting amphidromy or as euryhaline marine wanderers. Our data indicate two attempts of landward exploration via brackish water: phase 1 in which the outer portion of estuaries were colonized by olenids (Furongian-early late Tremadocian) and phase 2 involving exploration of the inner to middle estuarine zones by asaphids (Dapingian-Darriwilian). This study indicates that tolerance to salinity stress arose independently among different trilobite groups.

Efficacy of Anodal Suboccipital Direct Current Stimulation for Endogenous Pain Modulation and Tonic Thermal Pain Control in Healthy Participants: A Randomized Controlled Clinical Trial.

OBJECTIVE: The aim of this study was to assess whether anodal DCS applied to the suboccipital (SO) target area could potentiate antinociception assessed primarily with conditioned pain modulation of tonic thermal test stimuli. DESIGN: Randomized double-blinded control trial. SETTING: Rehabilitation hospital. SUBJECTS: Healthy participants. METHODS: Forty healthy participants were randomized to receive either SO-DCS or M1-DCS. The 20-minute 1.5 mA anodal or sham DCS intervention were applied to each participant in randomized order during two test sessions. The primary outcome measure included heterotopic cold-pressor conditioned pain modulation (CPM) of tonic heat pain. Secondary measures included pressure pain threshold and tonic thermal pain intensity. RESULTS: Heterotopic CPM of tonic heat pain intensity was unaffected by either SO-DCS or active M1, including the secondary measures of pressure pain threshold and tonic thermal pain intensity. Although low-power non-significant interactions were identified for DCS intervention (active versus sham) and time (before and after), a significant within-group inhibition of tonic cold pain was identified following SO-DCS (P = .011, mean [SD]: -0.76 ± 0.88 points) and M1-DCS (P < .002: -0.84 ± 0.82 points), without a significant change following sham DCS. CONCLUSIONS: Although heterotopic CPM was not facilitated with either SO-DCS or M1-DCS, a general significant inhibition of tonic cold pain intensity was demonstrated following both interventions. The general effects of active DCS compared to sham on tonic cold pain-irrespective of the M1 or SO target-need to be confirmed using standard quantitative sensory testing.

Transcranial direct current stimulation combined with robotic therapy for upper and lower limb function after stroke: a systematic review and meta-analysis of randomized control trials.

BACKGROUND: Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation method able to modulate neuronal activity after stroke. The aim of this systematic review was to determine if tDCS combined with robotic therapy (RT) improves limb function after stroke when compared to RT alone. METHODS: A search for randomized controlled trials (RCTs) published prior to July 15, 2021 was performed. The main outcome was function assessed with the Fugl-Meyer motor assessment for upper extremities (FM/ue) and 10-m walking test (10MWT) for the lower limbs. As secondary outcomes, strength was assessed with the Motricity Index (MI) or Medical Research Council scale (MRC), spasticity with the modified Ashworth scale (MAS), functional independence with the Barthel Index (BI), and kinematic parameters. RESULTS: Ten studies were included for analysis (n = 368 enrolled participants). The results showed a non-significant effect for tDCS combined with RT to improve upper limb function [standardized mean difference (SMD) = - 0.12; 95% confidence interval (CI): - 0.35-0.11)]. However, a positive effect of the combined therapy was observed in the lower limb function (SMD = 0.48; 95% CI: - 0.15-1.12). Significant results favouring tDCS combined with RT were not found in strength (SMD = - 0.15; 95% CI: - 0.4-0.1), spasticity [mean difference (MD) = - 0.15; 95% CI: - 0.8-0.5)], functional independence (MD = 2.5; 95% CI: - 1.9-6.9) or velocity of movement (SMD = 0.06; 95% CI: - 0.3-0.5) with a "moderate" or "low" recommendation level according to the GRADE guidelines. CONCLUSIONS: Current findings suggest that tDCS combined with RT does not improve upper limb function, strength, spasticity, functional independence or velocity of movement after stroke. However, tDCS may enhance the effects of RT alone for lower limb function. tDCS parameters and the stage or type of stroke injury could be crucial factors that determine the effectiveness of this therapy.

Effects of Dry Needling on Biomechanical Properties of the Myofascial Trigger Points Measured by Myotonometry: A Randomized Controlled Trial.

OBJECTIVE: The purpose of the present study was to examine the effect of dry needling (DN) on the biomechanical properties of a latent medial myofascial trigger point (MTrP) of the soleus muscle compared with an adjacent point within the taut band (TB) measured by myotonometry. METHODS: Fifty asymptomatic volunteers were randomly assigned to an intervention group (n = 26) or control group (n = 24). One session of DN was performed in every group as follows: 10 needle insertions into the MTrP area (intervention group) or TB area (control group). Myotonometric measurements (frequency, decrement, and stiffness) were performed at baseline (pre-intervention) and after the intervention (post-intervention) in both locations (MTrP and TB areas). RESULTS: The results showed that stiffness outcome significantly decreased with a large effect size after DN in the MTrP when measured in the MTrP location (P = .002; d = 0.928) but not when measured in the TB location. In contrast, no significant changes were observed in any location when the TB was needled (P > .05). CONCLUSIONS: The findings suggest that only DN into the MTrP area was effective in decreasing stiffness outcome, therefore a specific puncture was needed to modify myofascial muscle stiffness.

Towards a phenomenological based model for predicting the hardness of a processed meat product.

This study aims to build a model for predicting the hardness of meat products by considering their protein fractions and protein structural changes during production. Protein solubility is considered an indicator of protein structural changes. The obtained model results show that structural changes of sarcoplasmic and myofibrillar proteins occur during production. The gelling capacity is formed by the effect of the three protein fractions, namely myofibrillar, sarcoplasmic and stromal. The obtained model allows the prediction of the hardness of meat products based on their protein fraction contents with error below 5%, thus reaching a significant adjustment between real process data and the simulated model.

20-kHz alternating current stimulation: effects on motor and somatosensory thresholds.

BACKGROUND: High frequency alternating current (HFAC) stimulation have been shown to produce a peripheral nerve conduction block. Currently, all the studies applying HFAC stimulation in clinical studies, have employed frequencies below 10 kHz. The main aim of this work was to investigate the neuromodulatory effect of transcutaneous 20 kHz stimulation on somatosensory and pain thresholds, and maximal handgrip strength. METHODS: A randomized, crossover, single-blinded, placebo-controlled trial was conducted following recruitment of fourteen healthy volunteers. Transcutaneous stimulation at 20 kHz and sham stimulation were applied over the ulnar and median nerves of fourteen healthy volunteers for 20 min. Maximal handgrip strength (MHS), mechanical detection threshold (MDT) and pressure pain threshold (PPT) were registered prior to, during (15 min), immediately after the end (20 min), and 10 min following stimulation. RESULTS: The 20 kHz stimulation showed a lower MHS during the stimulation at the 15 min (30.1 kgs SE 2.8) and at 20 min (31.8 kgs, SE 2.8) when compared to sham stimulation (35.1 kgs, SE 3.4; p < 0.001 and 34.2 kgs, SE 3.4; p = 0.03, respectively). The 20 kHz stimulation resulted in a slight increase in MDT at 15 min (0.25 mN; 0.25-2.00) when compared to the sham stimulation (0.25 mN; 0.25-0.25; p = 0.02), and no effects were showed for PPT. CONCLUSIONS: High-frequency stimulation at 20 kHz suggests a partial block of nerve activity. Studies in subjects with neurological disorders characterized by nerve hyperactivity are needed to confirm the clinical impact of this non-invasive electrical stimulation technique. TRIAL REGISTRATION: NCT, NCT02837458. Registered on 12 April 2017.

Efficacy of high-intensity laser therapy in subacromial impingement syndrome: a three-month follow-up controlled clinical trial.

OBJECTIVES: To evaluate the effectiveness of high-intensity laser therapy on shoulder pain and function in subacromial impingement syndrome. DESIGN: Clinical controlled trial with alternate allocation. SETTING: Hospital Department of Rehabilitation. SUBJECTS: A total of 46 participants with subacromial impingement syndrome. INTERVENTION: Participants were sequence allocated to an intervention group (high-intensity laser therapy + exercise therapy) and control group (sham-laser + exercise therapy) and received 15 sessions (five days a week during three weeks). MAIN MEASURES: Patiens were evaluated at baseline, after 15 sessions, and at one month and at three months after completing the intervention. The main outcome variables were pain and functionality as measured by visual analogue scale; pressure pain threshold; Shoulder Pain and Disability Index; Constant-Murley Score; and QuickDASH. Secondary outcomes were number of sessions at discharge and drug use. RESULTS: A total of 21 patients in high-intensity laser therapy group (56.7 ± 8.9 years) and 22 patients in sham-laser group (61.3 ± 8.9 years) concluded the study. Visual analogue scale (cm) at baseline, one-month, and three-months were 6.2 ± 0.5, 3 ± 2.6, and 2.6 ± 2.4 for the control group and 5.4 ± 1.5, 3.6 ± 1.3, and 1.8 ± 1.7 for experimental group, respectively. Shoulder Pain and Disability Index (points) at baseline, one-month, and three-monts were 51.8 ± 16.1, 16.3 ± 16.1, and 13.6 ± 17.1 in the control group and 41.8 ± 20.6, 20.5 ± 19.7, 11 ± 14.5 in experimental group, respectively. No differences were found between groups ( P > 0.05). CONCLUSION: The effect of high-intensity laser therapy plus exercise is not higher than exercise alone to reduce pain and improve functionality in patients with subacromial syndrome.

Metabolic Profiling of the Soft Coral Erythropodium caribaeorum (Alcyonacea: Anthothelidae) from the Colombian Caribbean Reveals Different Chemotypes.

The Caribbean soft coral Erythropodium caribaeorum is a rich source of erythrolides-chlorinated briarane diterpenoids. These compounds have an ecological role as feeding deterrents, with a wide variation in their composition depending on the location where the sample is collected. In Colombia, this soft coral can be found at different locations in the Caribbean Sea including Santa Marta, Islas del Rosario, and Providencia-three environmentally different coral reef areas in the south and southwest Caribbean Sea. In order to evaluate differences in erythrolide composition, the metabolic profiles of samples from each of these locations were analyzed by HPLC-MS. Principal component analysis showed changes in the diterpene composition according to the sample origin. Diterpenes from samples collected at each location were isolated to describe the three chemotypes. The chemotype from Santa Marta was highly diverse, with the new erythrolides W and X together with eight known erythrolides. The sample from Islas del Rosario showed a low diversity chemotype constituted by high amounts of erythrolide A and B. The chemotype from Providencia showed low chemical diversity with only two main compounds-erythrolide V and R. Evaluation of cytotoxic activity against the human cancer cell lines PC-3, MCF7, and A549 showed erythrolides A and B as the more active compounds with IC50 values in the range from 2.45 to 30 µM.

Combining transcranial direct-current stimulation with gait training in patients with neurological disorders: a systematic review.

BACKGROUND: Transcranial direct-current stimulation (tDCS) is an easy-to-apply, cheap, and safe technique capable of affecting cortical brain activity. However, its effectiveness has not been proven for many clinical applications. OBJECTIVE: The aim of this systematic review was to determine whether the effect of different strategies for gait training in patients with neurological disorders can be enhanced by the combined application of tDCS compared to sham stimulation. Additionally, we attempted to record and analyze tDCS parameters to optimize its efficacy. METHODS: A search in Pubmed, PEDro, and Cochrane databases was performed to find randomized clinical trials that combined tDCS with gait training. A chronological filter from 2010 to 2018 was applied and only studies with variables that quantified the gait function were included. RESULTS: A total of 274 studies were found, of which 25 met the inclusion criteria. Of them, 17 were rejected based on exclusion criteria. Finally, 8 trials were evaluated that included 91 subjects with stroke, 57 suffering from Parkinson's disease, and 39 with spinal cord injury. Four of the eight assessed studies did not report improved outcomes for any of its variables compared to the placebo treatment. CONCLUSIONS: There are no conclusive results that confirm that tDCS can enhance the effect of the different strategies for gait training. Further research for specific pathologies, with larger sample sizes and adequate follow-up periods, are required to optimize the existing protocols for applying tDCS.