Potassium rhythms couple the circadian clock to the cell cycle.

Circadian (~24 h) rhythms are a fundamental feature of life, and their disruption increases the risk of infectious diseases, metabolic disorders, and cancer1-6. Circadian rhythms couple to the cell cycle across eukaryotes7,8 but the underlying mechanism is unknown. We previously identified an evolutionarily conserved circadian oscillation in intracellular potassium concentration, [K+]i9,10. As critical events in the cell cycle are regulated by intracellular potassium11,12, an enticing hypothesis is that circadian rhythms in [K+]i form the basis of this coupling. We used a minimal model cell, the alga Ostreococcus tauri, to uncover the role of potassium in linking these two cycles. We found direct reciprocal feedback between [K+]i and circadian gene expression. Inhibition of proliferation by manipulating potassium rhythms was dependent on the phase of the circadian cycle. Furthermore, we observed a total inhibition of cell proliferation when circadian gene expression is inhibited. Strikingly, under these conditions a sudden enforced gradient of extracellular potassium was sufficient to induce a round of cell division. Finally, we provide evidence that interactions between potassium and circadian rhythms also influence proliferation in mammalian cells. These results establish circadian regulation of intracellular potassium levels as a primary factor coupling the cell- and circadian cycles across diverse organisms.

Timely Questions Emerging in Chronobiology: The Circadian Clock Keeps on Ticking.

Chronobiology investigations have revealed much about cellular and physiological clockworks but we are far from having a complete mechanistic understanding of the physiological and ecological implications. Here we present some unresolved questions in circadian biology research as posed by the editorial staff and guest contributors to the Journal of Circadian Rhythms. This collection of ideas is not meant to be comprehensive but does reveal the breadth of our observations on emerging trends in chronobiology and circadian biology. It is amazing what could be achieved with various expected innovations in technologies, techniques, and mathematical tools that are being developed. We fully expect strengthening mechanistic work will be linked to health care and environmental understandings of circadian function. Now that most clock genes are known, linking these to physiological, metabolic, and developmental traits requires investigations from the single molecule to the terrestrial ecological scales. Real answers are expected for these questions over the next decade. Where are the circadian clocks at a cellular level? How are clocks coupled cellularly to generate organism level outcomes? How do communities of circadian organisms rhythmically interact with each other? In what way does the natural genetic variation in populations sculpt community behaviors? How will methods development for circadian research be used in disparate academic and commercial endeavors? These and other questions make it a very exciting time to be working as a chronobiologist.

Quadriceps muscle reaction time in obese children.

This study aimed to determine the influence of obesity, according to body mass index (BMI) and fat mass percentage, on quadriceps muscle reaction times. The study utilized a cross-sectional design. The sample size consisted of 42 schoolchildren (54.5% girls) aged 11 to 12 years old. Participant measurements included weight and height, which were used to categorize individuals based on BMI. Additionally, the electrical bioimpedance technique was employed to categorize participants based on their body fat percentage. A sudden destabilization test of the lower limb was performed to assess the reaction time of the rectus femoris, vastus medialis, and vastus lateralis muscles. The results show that overweight/obese children have a longer muscle reaction time for both the rectus femoris (ß = 18.13; p = 0.048) and the vastus lateralis (ß = 14.51; p = 0.042). Likewise, when the children were classified by percentage of body fat the results showed that overfat/obese children have a longer muscle reaction time for both the rectus femoris (ß = 18.13; p = 0.048) and the vastus lateralis (ß = 14.51; p = 0.042). Our results indicate that BMI and fat mass classification negativity alter the muscle reaction time in children. Overweight/obese or overfat/obese children showed longer reaction times in the rectus femoris and vastus lateralis muscles compared to children with normal weight. Based on these findings, it is suggested that in overweight and obese children, efforts not only focus on reducing body weight but that be complemented with training and/or rehabilitation programs that focus on preserving the normal physiological function of the musculoskeletal system.

Recurrent alcohol-associated hepatitis is common and is associated with increased mortality.

BACKGROUND AND AIMS: Alcohol relapse after surviving an episode of alcohol-associated hepatitis (AH) is common. However, the clinical features, risk factors, and prognostic implications of recurrent alcohol-associated hepatitis (RAH) are not well described. APPROACH AND RESULTS: A registry-based study was done of patients admitted to 28 Spanish hospitals for an episode of AH between 2014 and 2021. Baseline demographics and laboratory variables were collected. Risk factors for RAH were investigated using Cox regression analysis. We analyzed the severity of the index episodes of AH and compared it to that of RAH. Long-term survival was assessed by Kaplan-Meier curves and log-rank tests. A total of 1118 patients were included in the analysis, 125 (11%) of whom developed RAH during follow-up (median: 17 [7-36] months). The incidence of RAH in patients resuming alcohol use was 22%. The median time to recurrence was 14 (8-29) months. Patients with RAH had more psychiatric comorbidities. Risk factors for developing RAH included age <50 years, alcohol use >10 U/d, and history of liver decompensation. RAH was clinically more severe compared to the first AH (higher MELD, more frequent ACLF, and HE). Moreover, alcohol abstinence during follow-up was less common after RAH (18% vs. 45%, p <0.001). Most importantly, long-term mortality was higher in patients who developed RAH (39% vs. 21%, p = 0.026), and presenting with RAH independently predicted high mortality (HR: 1.55 [1.11-2.18]). CONCLUSIONS: RAH is common and has a more aggressive clinical course, including increased mortality. Patients surviving an episode of AH should undergo intense alcohol use disorder therapy to prevent RAH.

Enhancement of Strawberry Shelf Life via a Multisystem Coating Based on Lippia graveolens Essential Oil Loaded in Polymeric Nanocapsules.

Strawberries (Fragaria xannanasa) are susceptible to mechanical, physical, and physiological damage, which increases their incidence of rot during storage. Therefore, a method of protection is necessary in order to minimize quality losses. One way to achieve this is by applying polymer coatings. In this study, multisystem coatings were created based on polymer nanocapsules loaded with Lippia graveolens essential oil, and it was found to have excellent optical, mechanical, and water vapor barrier properties compared to the control (coating formed with alginate and with nanoparticles without the essential oil). As for the strawberries coated with the multisystem formed from the polymer nanocapsules loaded with the essential oil of Lippia graveolens, these did not present microbial growth and only had a loss of firmness of 17.02% after 10 days of storage compared to their initial value. This study demonstrated that the multisystem coating formed from the polymer nanocapsules loaded with the essential oil of Lippia graveolens could be a viable alternative to preserve horticultural products for longer storage periods.

Transcranial magnetic stimulation therapy for central post-stroke pain: systematic review and meta-analysis.

Introduction: Although rare, central post-stroke pain remains one of the most refractory forms of neuropathic pain. It has been reported that repetitive transcranial magnetic stimulation (rTMS) may be effective in these cases of pain. Aim: The aim of this study was to investigate the efficacy of rTMS in patients with central post-stroke pain (CPSP). Methods: We included randomized controlled trials or Controlled Trials published until October 3rd, 2022, which studied the effect of rTMS compared to placebo in CPSP. We included studies of adult patients (>18 years) with a clinical diagnosis of stroke, in which the intervention consisted of the application of rTMS to treat CSP. Results: Nine studies were included in the qualitative analysis; 6 studies (4 RCT and 2 non-RCT), with 180 participants, were included in the quantitative analysis. A significant reduction in CPSP was found in favor of rTMS compared with sham, with a large effect size (SMD: -1.45; 95% CI: -1.87; -1.03; p < 0.001; I2: 58%). Conclusion: The findings of the present systematic review with meta-analysis suggest that there is low quality evidence for the effectiveness of rTMS in reducing CPSP. Systematic review registration: Identifier (CRD42022365655).

Is iron overload associated with worse outcomes in patients with chronic liver disease undergoing liver transplantation?

Background: Iron overload is frequent in patients with chronic liver disease, associated with shorter survival after liver transplantation in patients with hereditary hemochromatosis. Its effect on patients without hereditary hemochromatosis is unclear. The aim of the study was to study the clinical impact of iron overload in patients who underwent liver transplantation at an academic tertiary referral center. Methods: We performed a retrospective cohort study including all patients without hereditary hemochromatosis who underwent liver transplantation from 2015 to 2017 at an academic tertiary referral center in Mexico City. Explant liver biopsies were reprocessed to obtain the histochemical hepatic iron index, considering a score ≥ 0.15 as iron overload. Baseline characteristics were compared between patients with and without iron overload. Survival was estimated using the Kaplan-Meier method, compared with the log-rank test and the Cox proportional hazards model. Results: Of 105 patients included, 45% had iron overload. Viral and metabolic etiologies, alcohol consumption, and obesity were more frequent in patients with iron overload than in those without iron overload (43% vs. 21%, 32% vs. 22%, p = 0.011; 34% vs. 9%, p = 0.001; and 32% vs. 12%, p = 0.013, respectively). Eight patients died within 90 days after liver transplantation (one with iron overload). Complication rate was higher in patients with iron overload versus those without iron overload (223 vs. 93 events/100 personmonths; median time to any complication of 2 vs. 3 days, p = 0.043), without differences in complication type. Fatality rate was lower in patients with iron overload versus those without iron overload (0.7 vs. 4.5 deaths/100 person-months, p = 0.055). Conclusion: Detecting iron overload might identify patients at risk of early complications after liver transplantation. Further studies are required to understand the role of iron overload in survival.

Assessing greenhouse gas emissions in Cuban agricultural soils: Implications for climate change and rice (Oryza sativa L.) production.

Assessing the impact of greenhouse gas (GHG) emissions on agricultural soils is crucial for ensuring food production sustainability in the global effort to combat climate change. The present study delves to comprehensively assess GHG emissions in Cuba's agricultural soil and analyze its implications for rice production and climate change because of its rich agriculture cultivation tradition and diverse agro-ecological zones from the period of 1990-2022. In this research, based on Autoregressive Distributed Lag (ARDL) approach the empirical findings depicts that in short run, a positive and significant impact of 1.60 percent % in Cuba's rice production. The higher amount of atmospheric carbon dioxide (CO2) levels improves photosynthesis, and stimulates the growth of rice plants, resulting in greater grain yields. On the other hand, rice production index raising GHG emissions from agriculture by 0.35 % in the short run. Furthermore, a significant and positive impact on rice production is found in relation to the farm machinery i.e., 3.1 %. Conversely, an adverse and significant impact of land quality was observed on rice production i.e., -5.5 %. The reliability of models was confirmed by CUSUM and CUSUM square plot. Diagnostic tests ensure the absence of serial correlation and heteroscedasticity in the models. Additionally, the forecasting results are obtained from the three machine learning models i.e. feed forward neural network (FFNN), support vector machines (SVM) and adaptive boosting technique (Adaboost). Through the % MAPE criterion, it is evident that FFNN has achieved high precision (91 %). Based on the empirical findings, the study proposed the adoption of sustainable agricultural practices and incentives should be given to the farmers so that future generations inherit a world that is sustainable, and healthy.

Effects of Physical Exercise on Telomere Length in Healthy Adults: Systematic Review, Meta-Analysis, and Meta-Regression.

BACKGROUND: Physical exercise is one of the main nonpharmacological treatments for most pathologies. In addition, physical exercise is beneficial in the prevention of various diseases. The impact of physical exercise has been widely studied; however, existing meta-analyses have included diverse and heterogeneous samples. Therefore, to our knowledge, this is the first meta-analysis to evaluate the impact of different physical exercise modalities on telomere length in healthy populations. OBJECTIVE: In this review, we aimed to determine the effect of physical exercise on telomere length in a healthy population through a meta-analysis of randomized controlled trials. METHODS: A systematic review with meta-analysis and meta-regression of the published literature on the impact of physical exercise on telomere length in a healthy population was performed. PubMed, Cochrane Library, SCOPUS, Web of Science, and Embase databases were searched for eligible studies. Methodological quality was evaluated using the Risk Of Bias In Nonrandomized Studies of Interventions and the risk-of-bias tool for randomized trials. Finally, the certainty of our findings (closeness of the estimated effect to the true effect) was evaluated using Grading of Recommendations, Assessment, Development, and Evaluations (GRADE). RESULTS: We included 9 trials that met the inclusion criteria with fair methodological quality. Random-effects model analysis was used to quantify the difference in telomere length between the exercise and sham groups. Meta-analysis showed that exercise did not significantly increase telomere length compared with the control intervention (mean difference=0.0058, 95% CI -0.05 to 0.06; P=.83). Subgroup analysis suggested that high-intensity interventional exercise significantly increased telomere length compared with the control intervention in healthy individuals (mean difference=0.15, 95% CI 0.03-0.26; P=.01). Furthermore, 56% of the studies had a high risk of bias. Certainty was graded from low to very low for most of the outcomes. CONCLUSIONS: The findings of this systematic review and meta-analysis suggest that high-intensity interval training seems to have a positive effect on telomere length compared with other types of exercise such as resistance training or aerobic exercise in a healthy population. TRIAL REGISTRATION: PROSPERO CRD42022364518; http://tinyurl.com/4fwb85ff.

Peptidyl nitroalkene inhibitors of main protease rationalized by computational and crystallographic investigations as antivirals against SARS-CoV-2.

The coronavirus disease 2019 (COVID-19) pandemic continues to represent a global public health issue. The viral main protease (Mpro) represents one of the most attractive targets for the development of antiviral drugs. Herein we report peptidyl nitroalkenes exhibiting enzyme inhibitory activity against Mpro (Ki: 1-10 µM) good anti-SARS-CoV-2 infection activity in the low micromolar range (EC50: 1-12 µM) without significant toxicity. Additional kinetic studies of compounds FGA145, FGA146 and FGA147 show that all three compounds inhibit cathepsin L, denoting a possible multitarget effect of these compounds in the antiviral activity. Structural analysis shows the binding mode of FGA146 and FGA147 to the active site of the protein. Furthermore, our results illustrate that peptidyl nitroalkenes are effective covalent reversible inhibitors of the Mpro and cathepsin L, and that inhibitors FGA145, FGA146 and FGA147 prevent infection against SARS-CoV-2.

Transcending frontiers in prostate cancer: the role of oncometabolites on epigenetic regulation, CSCs, and tumor microenvironment to identify new therapeutic strategies.

Prostate cancer, as one of the most prevalent malignancies in males, exhibits an approximate 5-year survival rate of 95% in advanced stages. A myriad of molecular events and mutations, including the accumulation of oncometabolites, underpin the genesis and progression of this cancer type. Despite growing research demonstrating the pivotal role of oncometabolites in supporting various cancers, including prostate cancer, the root causes of their accumulation, especially in the absence of enzymatic mutations, remain elusive. Consequently, identifying a tangible therapeutic target poses a formidable challenge. In this review, we aim to delve deeper into the implications of oncometabolite accumulation in prostate cancer. We center our focus on the consequential epigenetic alterations and impacts on cancer stem cells, with the ultimate goal of outlining novel therapeutic strategies.

Characterization of humoral responses to Nipah virus infection in the Syrian Hamster model of disease.

Nipah virus (NiV) is a highly pathogenic paramyxovirus. The Syrian hamster model recapitulates key features of human NiV disease and is a critical tool for evaluating antivirals and vaccines. Here we describe longitudinal humoral immune responses in NiV-infected Syrian hamsters. Samples were obtained 1-28 days after infection and analyzed by ELISA, neutralization, and Fc-mediated effector function assays. NiV infection elicited robust antibody responses against the nucleoprotein and attachment glycoprotein. Levels of neutralizing antibodies were modest and only detectable in surviving animals. Fc-mediated effector functions were mostly observed in nucleoprotein-targeting antibodies. Antibody levels and activities positively correlated with challenge dose.

In Vitro and In Vivo Antileishmanial Activity of Thioridazine.

INTRODUCTION: Leishmaniasis is a neglected disease with high prevalence and incidence in tropical and subtropical areas. Existing drugs are limited due to cost, toxicity, declining efficacy and unavailability in endemic places. Drug repurposing has established as an efficient way for the discovery of drugs for a variety of diseases. PURPOSE: The objective of the present work was testing the antileishmanial activity of thioridazine, an antipsychotic agent with demonstrated effect against other intracellular pathogens. METHODS: The cytotoxicity for mouse peritoneal macrophages as well as the activity against Leishmania amazonensis, Leishmania mexicana and Leishmania major promastigotes and intracellular amastigotes, as well as in a mouse model of cutaneous leishmaniasis, were assessed. RESULTS: Thioridazine inhibited the in vitro proliferation of promastigotes (50% inhibitory concentration-IC50-values in the range of 0.73 µM to 3.8 µM against L. amazonensis, L. mexicana and L. major) and intracellular amastigotes (IC50 values of 1.27 µM to 4.4 µM for the same species). In contrast, in mouse peritoneal macrophages, the 50% cytotoxic concentration was 24.0 ± 1.89 µM. Thioridazine inhibited the growth of cutaneous lesions and reduced the number of parasites in the infected tissue of mice. The dose of thioridazine that inhibited lesion development by 50% compared to controls was 23.3 ± 3.1 mg/kg and in terms of parasite load, it was 11.1 ± 0.97 mg/kg. CONCLUSIONS: Thioridazine was effective against the promastigote and intracellular amastigote stages of three Leishmania species and in a mouse model of cutaneous leishmaniasis, supporting the potential repurposing of this drug as an antileishmanial agent.

mRNA Levels of Aromatase, 5α-Reductase Isozymes, and Prostate Cancer-Related Genes in Plucked Hair from Young Men with Androgenic Alopecia.

Androgenic alopecia (AGA) is the most prevalent type of progressive hair loss and has psychological repercussions. Nevertheless, the effectiveness of current pharmacological treatments remains limited, in part because the molecular basis of the disease has not been fully elucidated. Our group previously highlighted the important roles of aromatase and 5α-reductase (5α-R) in alopecia in young women with female pattern hair loss. Additionally, an association has been proposed between AGA and prostate cancer (PCa), suggesting that genes implicated in PCa would also be involved in AGA. A low-invasive, sensitive, and precise method was used to determine mRNA levels of aromatase, 5α-R isozymes, and 84 PCa-related genes in samples of plucked hair from young men with AGA and controls. Samples were obtained with a trichogram from the vertex scalp, and mRNA levels were quantified using real-time RT-PCR. The men with AGA had significantly higher 5α-R2 mRNA levels in comparison to controls; interestingly, some of them also showed markedly elevated mRNA levels of 5α-R1 or 5α-R3 or of both, which may explain the varied response to 5α-R inhibitor treatments. The men with AGA also showed significant changes versus controls in 6 out of the 84 genes implicated in PCa. This study contributes greater knowledge of the molecular bases of AGA, facilitating early selection of the most appropriate pharmacological therapy and opening the way to novel treatments.

Antileishmanial activity of 5-nitroindazole derivatives.

Background: Currently, there is no safe and effective vaccine against leishmaniasis and existing therapies are inadequate due to high toxicity, cost and decreased efficacy caused by the emergence of resistant parasite strains. Some indazole derivatives have shown in vitro and in vivo activity against Trichomonas vaginalis and Trypanosoma cruzi. On that basis, 20 indazole derivatives were tested in vitro against Leishmania amazonensis. Objective: To evaluate the in vitro activity of twenty 2-benzyl-5-nitroindazolin-3-one derivatives against L. amazonensis. Design: For the selection of promising compounds, it is necessary to evaluate the indicators for in vitro activity. For this aim, a battery of studies for antileishmanial activity and cytotoxicity were implemented. These results enabled the determination of the substituents in the indazole derivatives responsible for activity and selectivity, through the analysis of the structure-activity relationship (SAR). Methods: In vitro cytotoxicity against mouse peritoneal macrophages and growth inhibitory activity in promastigotes were evaluated for 20 compounds. Compounds that showed adequate selectivity were tested against intracellular amastigotes. The SAR from the results in promastigotes was represented using the SARANEA software. Results: Eight compounds showed selectivity index >10% and 50% inhibitory concentration <1 µM against the promastigote stage. Against intracellular amastigotes, four were as active as Amphotericin B. The best results were obtained for 2-(benzyl-2,3-dihydro-5-nitro-3-oxoindazol-1-yl) ethyl acetate, with 50% inhibitory concentration of 0.46 ± 0.01 µM against amastigotes and a selectivity index of 875. The SAR study showed the positive effect on the selectivity of the hydrophilic fragments substituted in position 1 of 2-benzyl-5- nitroindazolin-3-one, which played a key role in improving the selectivity profile of this series of compounds. Conclusion: 2-bencyl-5-nitroindazolin-3-one derivatives showed selective and potent in vitro activity, supporting further investigations on this family of compounds as potential antileishmanial hits.

Draft genome sequence of Vibrio lentus VLO8, recovered from the larval culture of the Chilean scallop (Argopecten purpuratus).

This announcement reports the genome of Vibrio lentus VLO8 recovered from the larval culture of Chilean scallop. The genomes of strain VLO8 have two contigs with a total length of 5,499,980 bp, an average G + C content of 44.22%, a total number of protein-coding genes of 6,439, and 170 RNAs.

Development of Essential Oil-Loaded Polymeric Nanocapsules as Skin Delivery Systems: Biophysical Parameters and Dermatokinetics Ex Vivo Evaluation.

Essential oils (EOs) are natural antioxidant alternatives that reduce skin damage. However, EOs are highly volatile; therefore, their nanoencapsulation represents a feasible alternative to increase their stability and favor their residence time on the skin to guarantee their effect. In this study, EOs of Rosmarinus officinalis and Lavandula dentata were nanoencapsulated and evaluated as skin delivery systems with potential antioxidant activity. The EOs were characterized and incorporated into polymeric nanocapsules (NC-EOs) using nanoprecipitation. The antioxidant activity was evaluated using the ferric thiocyanate method. The ex vivo effects on pig skin were evaluated based on biophysical parameters using bioengineering techniques. An ex vivo dermatokinetic evaluation on pig skin was performed using modified Franz cells and the tape-stripping technique. The results showed that the EOs had good antioxidant activity (>65%), which was maintained after nanoencapsulation and purification. The nanoencapsulation of the EOs favored its deposition in the stratum corneum compared to free EOs; the highest deposition rate was obtained for 1,8-cineole, a major component of L. dentata, at 1 h contact time, compared to R. officinalis with a major deposition of the camphor component. In conclusion, NC-EOs can be used as an alternative antioxidant for skin care.

Artificial Neural Networks with Machine Learning Design for a Polyphasic Encoder.

Artificial neural networks are a powerful tool for managing data that are difficult to process and interpret. This article presents the design and implementation of backpropagated multilayer artificial neural networks, structured with a vector input, hidden layers, and an output node, for information processing generated by an optical encoder based on the polarization of light. A machine learning technique is proposed to train the neural networks such that the system can predict with remarkable accuracy the angular position in which the rotating element of the neuro-encoder is located based on information provided by light's phase-shifting arrangements. The proposed neural designs show excellent performance in small angular intervals, and a methodology was proposed to avoid losing this remarkable characteristic in measurements from 0 to 180° and even up to 360°. The neuro-encoder was implemented in the simulation stage to obtain performance results, where the main evaluation metric employed to assess the performance is the total error. This proposal can be useful to improve the capabilities of resolvers or other polyphasic sensors used to obtain outstanding precision and accurate data, even when working under hard and noisy industrial conditions.

Detergent-free parasite transformation and replication assay for drug screening against intracellular Leishmania amastigotes.

Leishmaniasis is an infectious disease caused by protozoan species in the genera Leishmania and Endotrypanum. Current antileishmanial drugs are limited due to adverse effects, variable efficacy, the development of resistant parasites, high cost, parenteral administration and lack of availability in endemic areas. Therefore, active searching for new antileishmanial drugs has been done for years, mainly by academia. Drug screening techniques have been a challenge since the intracellular localization of Leishmania amastigotes implies that the host cell may interfere with the quantification of the parasites and the final estimation of the effect. One of the procedures to avoid host cell interference is based on its detergent-mediated lysis and subsequent transformation of viable amastigotes into promastigotes, their proliferation and eventual quantification as an axenic culture of promastigotes. However, the use of detergent involves additional handling of cultures and variability. In the present work, cultures of intracellular amastigotes were incubated for 72 h at 26 °C after exposure to the test compounds and the transformation and proliferation of parasites took place without need of adding any detergent. The assay demonstrated clear differentiation of negative and positive controls (average Z´ = 0.75) and 50% inhibitory concentrations of compounds tested by this method and by the gold standard enumeration of Giemsa-stained cultures were similar (p = 0.5002) and highly correlated (r = 0.9707). This simplified procedure is less labor intensive, the probability of contamination and the experimental error are reduced, and it is appropriate for the automated high throughput screening of compounds.

Effectiveness of different percutaneous electrolysis protocols in the endogenous modulation of pain: A Double-Blinded Randomized Clinical Trial.

OBJECTIVE: This randomized clinical trial investigated if the application of percutaneous electrolysis (PE) enhances endogenous pain mechanisms (EPM) when compared with a simple needle application (acting as sham). METHODS: Forty-six asymptomatic subjects, aged 18-40 years, were randomized into three groups receiving a single ultrasound-guided PE intervention consisting of a needle insertion on the lateral epicondyle: sham (without electrical current), low-intensity (0.3 mA, 90s), or high-intensity (three pulses of 3 mA, 3s) PE. Widespread pressure pain thresholds (PPT), conditioned pain modulation (CPM), and temporal summation (TS) were bilaterally assessed in the lateral epicondyle, bicipital groove, transverse process of C5 and tibialis anterior muscle. Outcomes were obtained by an assessor blinded to the treatment allocation of the subjects. RESULTS: No significant changes in CPM were observed in either group (omnibus ANOVA all, P > .05). A significant bilateral increase in PPT in the lateral epicondyle in the high intensity group as compared with the sham group was observed (P < .01). A significant decrease of TS in both low (P = .002) and high (P = .049) intensity groups on the right, but not on the left, tibialis anterior was also observed when compared with the sham group. CONCLUSIONS: One session of PE is able to slightly stimulate modulatory pathways related to nociceptive gain, particularly pressure pain sensitivity and temporal summation but not conditioning pain modulation, when compared with a sham needle intervention, with changes even contralaterally. No significant differences were found between low- and high-intensity doses of percutaneous electrolysis.