Spatial summation of pain is associated with pain expectations: Results from a home-based paradigm.

The purpose of this study was to reproduce the previously observed spatial summation of pain effect (SSp) using non-laboratory procedures and commercial equipment. An additional aim was to explore the association between expectations and SSp. The Cold Pressor Task (CPT) was used to induce SSp. Healthy participants (N = 68) immersed their non-dominant hands (divided into 5 segments) into cold water (CPT). Two conditions were used 1) gradual hand immersion (ascending condition) and 2) gradual hand withdrawal (descending condition). Pain intensity was measured on a Visual Analogue Scale (VAS). Psychological factors, such as the participants' expectations of pain intensity were also measured on a VAS. Results showed significant SSp (χ2(4) = 116.90, p < 0.001), reproduced with non-laboratory equipment in a home-based set-up. Furthermore, two novel findings were observed: i) there was a significant correlation between expectations and perceived pain, indicating a link between pain expectations and SSp, ii) spatial summation increased with the increase in duration exposure to the noxious stimulus (Wald χ2(8) = 80.80, p < 0.001). This study suggests that SSp is associated with pain expectations and can be formed by a mixture of excitatory and inhibitory mechanisms potentially driven by temporal characteristics of neural excitation. Moreover, this study proposes a new feasible way to induce SSp using a home-based set-up.

SMART System in the Assessment of Exercise Tolerance in Adults.

Health-oriented physical activity should meet two key criteria: safety and an optimal level of exercise. The system of monitoring and rationalization of training (SMART) was designed to meet them. SMART integrates a custom-configured inertial measurement unit (IMU) and a sensor with real-time heart rate measurement (HR) using a proprietary computer application. SMART was used to evaluate the safety and exercise load with 115 study participants: 51 women (44.35%) and 64 men (55.65%) aged 19 to 65 years. The exercise test was the 6MWT test. In 35% of the participants, the mean HR exceeded the recognized safe limit of HR 75% max. Ongoing monitoring of HR allows for optimal exercise and its safety. Step count data were collected from the SMART system. The average step length was calculated by dividing the distance by the number of steps. The aim of the present study was to assess the risk of excessive cardiovascular stress during the 6MWT test using the SMART system.

Specific patterns of coherence and phase lag index in particular regions as biomarkers of cognitive impairment in Parkinson's disease.

INTRODUCTION: Cognitive impairment is a persistent and increasingly reported symptom of patients with Parkinson's disease (PD), significantly affecting daily functioning quality. This study aims to evaluate the functional connectivity of the brain network in patients with Parkinson's disease with various severities of cognitive decline using quantitative electroencephalography (EEG) analysis. METHODS: Based on the EEG recorded in the resting state, the coherence and phase lag index were calculated to evaluate functional connectivity in 108 patients with Parkinson's disease divided into three groups according to their cognitive condition: dementia due to PD (PD-D), PD and mild cognitive impairment (PD-MCI) and cognitively normal patients (PD-CogN). RESULTS: It was found that there were significantly different coherence values in the PD-D group compared to PD-CogN in different frequency bands. In most cases, there was a decrease in coherence in PD-D compared to PD-CogN. The most specific changes were revealed in the theta frequency band in the temporal right-frontal left and temporal right-frontal right regions. In the alpha frequency band, the most significant decreases were shown in the occipital right-frontal left and occipital left-frontal right areas. There were also statistically significant differences in phase lag index between many areas, especially in the theta frequency range. CONCLUSIONS: These findings indicate that the functional connectivity patterns of coherence and phase lag index - found in a particular frequency band and region - could become a reliable biomarker for identifying cognitive impairment and differentiating its severity in PD patients.

Cardiac status and atherosclerotic cardiovascular risk of convalescents after COVID-19 in Poland.

INTRODUCTION: The COVID­19 pandemic brought about cardiac complications and unfavorable lifestyle changes that may increase cardiovascular risk. OBJECTIVES: Our aim was to establish the cardiac status of convalescents several months after COVID­19, and the 10­year risk of fatal and nonfatal atherosclerotic cardiovascular disease (ASCVD) events, according to the Systemic Coronary Risk Estimation­2 (SCORE2) and SCORE2­Older Persons (OP) algorithms. PATIENTS AND METHODS: The study included 553 convalescents (mean [SD] age, 63.5 [10.26] years; 316 [57.1%] women), hospitalized at the Cardiac Rehabilitation Department, Ustron Health Resort, Poland. The history of cardiac complications, exercise capacity, blood pressure control, echocardiography, 24­hour Holter electrocardiogram recording, and laboratory workup were assessed. RESULTS: A total of 20.7% of men and 17.7% of women (P = 0.38) had cardiac complications during acute COVID­19, most often heart failure (10.7%), pulmonary embolism (3.7%), and supraventricular arrhythmias (6.3%). On average, 4 months after COVID­19 diagnosis, echocardiographic abnormalities were found in 16.7% of men and 9.7% of women (P = 0.1), and benign arrhythmias in 45.3% of men and 44% of women (P = 0.84). Preexisting ASCVD was reported in 21.8% of men and 6.1% of women (P <0.001). The median risk assessed by SCORE2/SCORE2­OP algorithms in apparently healthy people was high for the participants aged 40-49 years (3%; interquartile range [IQR], 2%-4%) and 50-69 years (8%; IQR, 5.3%-10%), and very high (20%; IQR, 15.5%-37%) for the participants aged 70 years and above. The SCORE2 risk in men aged over 70 years was higher than in women (P <0.001). CONCLUSIONS: Data collected in the convalescents indicate a relatively small number of cardiac problems that could be associated with a history of COVID­19 in either sex, and a high risk of ASCVD, especially in men.

The Increase of Theta Power and Decrease of Alpha/Theta Ratio as a Manifestation of Cognitive Impairment in Parkinson's Disease.

In this study, we aim to assess and examine cognitive functions in Parkinson's Disease patients using EEG recordings, with a central focus on characteristics associated with a cognitive decline. Based on neuropsychological evaluation using Mini-Mental State Examination, Montreal Cognitive Assessment, and Addenbrooke's Cognitive Examination-III, 98 participants were divided into three cognitive groups. All the particpants of the study underwent EEG recordings with spectral analysis. The results revealed an increase in the absolute theta power in patients with Parkinson's disease dementia (PD-D) compared to cognitively normal status (PD-CogN, p=0.00997) and a decrease in global relative beta power in PD-D compared to PD-CogN (p=0.0413). An increase in theta relative power in the left temporal region (p=0.0262), left occipital region (p=0.0109), and right occipital region (p=0.0221) were observed in PD-D compared to PD-N. The global alpha/theta ratio and global power spectral ratio significantly decreased in PD-D compared to PD-N (p = 0.001). In conclusion, the increase in relative theta power and the decrease in relative beta power are characteristic changes in EEG recordings in PD patients with cognitive impairment. Identifying these changes can be a useful biomarker and a complementary tool in the neuropsychological diagnosis of cognitive impairment in Parkinson's Disease.

Actual status and future directions of cardiac telerehabilitation.

Telerehabilitation (TR) was developed to achieve the same results as would be achieved by the standard rehabilitation process and to overcome potential geographical barriers and staff deficiencies. This is especially relevant in periodic crisis situations, including the recent COVID-19 pandemic. Proper execution of TR strategy requires both well-educated staff and dedicated equipment. Various studies have shown that TR may have similar effects to traditional rehabilitation in terms of clinical outcomes and may also reduce total healthcare costs per participant, including rehospitalization costs. However, as with any method, TR has its advantages and disadvantages, including a lack of direct contact or prerequisite, rudimentary ability of the patients to handle mobile devices, among other competencies. Herein, is a discussion of the current status of TR, focusing primarily on cardiac TR, describing some technical/organizational and legal aspects, highlighting the indications, examining cost-effectiveness, as well as outlining possible future directions.

Sensitivity and Specificity of Anthropometric Indices in Identifying Obesity in Women over 40 Years of Age and Their Variability in Subsequent Decades of Life.

Anthropometric measurements and indices are a simple and inexpensive method to assess normal physical development and quickly identify the risk of diseases. The aim of the study was to verify the sensitivity (Se) and specificity (Sp) of selected anthropometric indices in a group of women over 40 years. The study included 87 women (group I-40 to 49 years, group II-50 to 59 years, group III-60 to 69 years, and group IV-70 to 79 years). Anthropometric characteristics were measured: body mass (BM), body height (BH), waist circumference (WC), and hip circumference (HC). Body mass index (BMI), body adiposity index (BAI), waist-hip ratio (WHR), and waist-to-height ratio (WHTR) were calculated. The percentage of fat tissue (FT) and visceral fat volume (FV) were evaluated using DEXA. A decrease in mean BH with an increase in the mean WC, WHR, and WHTR in subsequent decades. There were strong statistically significant correlations between FT and most indicators (except for WHR). FV was correlated at a strong or moderate level with most parameters. In the group of women aged 40 to 80 years, the most favorable AUC was obtained for WC, followed by BMI. BAI can be recommended as a complementary indicator to BMI.

Running from Stress: Neurobiological Mechanisms of Exercise-Induced Stress Resilience.

Chronic stress, even stress of a moderate intensity related to daily life, is widely acknowledged to be a predisposing or precipitating factor in neuropsychiatric diseases. There is a clear relationship between disturbances induced by stressful stimuli, especially long-lasting stimuli, and cognitive deficits in rodent models of affective disorders. Regular physical activity has a positive effect on the central nervous system (CNS) functions, contributes to an improvement in mood and of cognitive abilities (including memory and learning), and is correlated with an increase in the expression of the neurotrophic factors and markers of synaptic plasticity as well as a reduction in the inflammatory factors. Studies published so far show that the energy challenge caused by physical exercise can affect the CNS by improving cellular bioenergetics, stimulating the processes responsible for the removal of damaged organelles and molecules, and attenuating inflammation processes. Regular physical activity brings another important benefit: increased stress robustness. The evidence from animal studies is that a sedentary lifestyle is associated with stress vulnerability, whereas a physically active lifestyle is associated with stress resilience. Here, we have performed a comprehensive PubMed Search Strategy for accomplishing an exhaustive literature review. In this review, we discuss the findings from experimental studies on the molecular and neurobiological mechanisms underlying the impact of exercise on brain resilience. A thorough understanding of the mechanisms underlying the neuroprotective potential of preconditioning exercise and of the role of exercise in stress resilience, among other things, may open further options for prevention and therapy in the treatment of CNS diseases.

Global Proteome Profiling of the Temporal Cortex of Female Rats Exposed to Chronic Stress and the Western Diet.

The increasing consumption of highly processed foods with high amounts of saturated fatty acids and simple carbohydrates is a major contributor to the burden of overweight and obesity. Additionally, an unhealthy diet in combination with chronic stress exposure is known to be associated with the increased prevalence of central nervous system diseases. In the present study, the global brain proteome approach was applied to explore protein alterations after exposure to the Western diet and/or stress. Female adult rats were fed with the Western diet with human snacks and/or subjected to chronic stress induced by social instability for 12 weeks. The consumption of the Western diet resulted in an obese phenotype and induced changes in the serum metabolic parameters. Consuming the Western diet resulted in changes in only 5.4% of the proteins, whereas 48% of all detected proteins were affected by chronic stress, of which 86.3% were down-regulated due to this exposure to chronic stress. However, feeding with a particular diet modified stress-induced changes in the brain proteome. The down-regulation of proteins involved in axonogenesis and mediating the synaptic clustering of AMPA glutamate receptors (Nptx1), as well as proteins related to metabolic processes (Atp5i, Mrps36, Ndufb4), were identified, while increased expression was detected for proteins involved in the development and differentiation of the CNS (Basp1, Cend1), response to stress, learning and memory (Prrt2), and modulation of synaptic transmission (Ncam1, Prrt2). In summary, global proteome analysis provides information about the impact of the combination of the Western diet and stress exposure on cerebrocortical protein alterations and yields insight into the underlying mechanisms and pathways involved in functional and morphological brain alterations as well as behavioral disturbances described in the literature.

Cerebrocortical proteome profile of female rats subjected to the western diet and chronic social stress.

The energy-dense western diet significantly increases the risk of obesity, type 2 diabetes, cardiovascular episodes, stroke, and cancer. Recently more attention has been paid to the contribution of an unhealthy lifestyle on the development of central nervous system disorders. Exposure to long-lasting stress is one of the key lifestyle modifications associated with the increased prevalence of obesity and metabolic diseases. The main goal of the present study was to verify the hypothesis that exposure to chronic stress modifies alterations in the brain proteome induced by the western diet. Female adult rats were fed with the prepared chow reproducing the human western diet and/or subjected to chronic stress induced by social instability for 6 weeks. A control group of lean rats were fed with a standard diet. Being fed with the western diet resulted in an obese phenotype and induced changes in the serum metabolic parameters. The combination of the western diet and chronic stress exposure induced more profound changes in the rat cerebrocortical proteome profile than each of these factors individually. The down-regulation of proteins involved in neurotransmitter secretion (Rph3a, Snap25, Syn1) as well as in learning and memory processes (Map1a, Snap25, Tnr) were identified, while increased expression was detected for 14-3-3 protein gamma (Ywhag) engaged in the modulation of the insulin-signaling cascade in the brain. An analysis of the rat brain proteome reveals important changes that indicate that a combination of the western diet and stress exposure may lead to impairments of neuronal function and signaling.

Effects of Simultaneous Exposure to a Western Diet and Wheel-Running Training on Brain Energy Metabolism in Female Rats.

BACKGROUND: In the pathogenesis of central nervous system disorders (e.g., neurodegenerative), an important role is attributed to an unhealthy lifestyle affecting brain energy metabolism. Physical activity in the prevention and treatment of lifestyle-related diseases is getting increasing attention. METHODS: We performed a series of assessments in adult female Long Evans rats subjected to 6 weeks of Western diet feeding and wheel-running training. A control group of lean rats was fed with a standard diet. In all experimental groups, we measured physiological parameters (animal weights, body composition, serum metabolic parameters). We assessed the impact of simultaneous exposure to a Western diet and wheel-running on the cerebrocortical protein expression (global proteomic profiling), and in the second part of the experiment, we measured the cortical levels of protein related to brain metabolism (Western blot). RESULTS: Western diet led to an obese phenotype and induced changes in the serum metabolic parameters. Wheel-running did not reduce animal weights or fat mass but significantly decreased serum glucose level. The global proteome analysis revealed that the altered proteins were functionally annotated as they were involved mostly in metabolic pathways. Western blot analysis showed the downregulation of the mitochondrial protein-Acyl-CoA dehydrogenase family member 9, hexokinase 1 (HK1)-enzyme involved in principal glucose metabolism pathways and monocarboxylate transporter 2 (MCT2). Wheel-running reversed this decline in the cortical levels of HK1 and MCT2. CONCLUSION: The cerebrocortical proteome is affected by a combination of physical activity and Western diet in female rats. An analysis of the cortical proteins involved in brain energy metabolism provides a valuable basis for the deeper investigation of changes in the brain structure and function induced by simultaneous exposure to a Western diet and physical activity.

Differential Response of Hippocampal and Cerebrocortical Autophagy and Ketone Body Metabolism to the Ketogenic Diet.

Experimental and clinical data support the neuroprotective properties of the ketogenic diet and ketone bodies, but there is still a lot to discover to comprehensively understand the underlying mechanisms. Autophagy is a key mechanism for maintaining cell homeostasis, and therefore its proper function is necessary for preventing accelerated brain aging and neurodegeneration. Due to many potential interconnections, it is possible that the stimulation of autophagy may be one of the mediators of the neuroprotection afforded by the ketogenic diet. Recent studies point to possible interconnections between ketone body metabolism and autophagy. It has been shown that autophagy is essential for hepatic and renal ketogenesis in starvation. On the other hand, exogenous ketone bodies modulate autophagy both in vitro and in vivo. Many regional differences occur between brain structures which concern i.e., metabolic responses and autophagy dynamics. The aim of the present study was to evaluate the influence of the ketogenic diet on autophagic markers and the ketone body utilizing and transporting proteins in the hippocampus and frontal cortex. C57BL/6N male mice were fed with two ketogenic chows composed of fat of either animal or plant origins for 4 weeks. Markers of autophagosome formation as well as proteins associated with ketolysis (BDH1-3-hydroxybutyrate dehydrogenase 1, SCOT/OXCT1-succinyl CoA:3-oxoacid CoA transferase), ketone transport (MCT1-monocarboxylate transporter 1) and ketogenesis (HMGCL, HMGCS2) were measured. The hippocampus showed a robust response to nutritional ketosis in both changes in the markers of autophagy as well as the levels of ketone body utilizing and transporting proteins, which was also accompanied by increased concentrations of ketone bodies in this brain structure, while subtle changes were observed in the frontal cortex. The magnitude of the effects was dependent on the type of ketogenic diet used, suggesting that plant fats may exert a more profound effect on the orchestrated upregulation of autophagy and ketone body metabolism markers. The study provides a foundation for a deeper understanding of the possible interconnections between autophagy and the neuroprotective efficacy of nutritional ketosis.

Upregulation of hepatic autophagy under nutritional ketosis.

Many of the metabolic effects evoked by the ketogenic diet mimic the actions of fasting and the benefits of the ketogenic diet are often attributed to these similarities. Since fasting is a potent autophagy inductor in vivo and in vitro it has been hypothesized that the ketogenic diet may upregulate autophagy. The aim of the present study was to provide a comprehensive evaluation of the influence of the ketogenic diet on the hepatic autophagy. C57BL/6N male mice were fed with two different ketogenic chows composed of fat of either animal or plant origin for 4 weeks. To gain some insight into the time frame for the induction of autophagy on the ketogenic diet, we performed a short-term experiment in which animals were fed with ketogenic diets for only 24 or 48 h. The results showed that autophagy is upregulated in the livers of animals fed with the ketogenic diet. Moreover, the size of the observed effect was likely dependent on the diet composition. Subsequently, the markers of regulatory pathways that may link ketogenic diet action to autophagy were measured, i.e., the activity of mTORC1, activation of AMPK, and the levels of SIRT1, p53, and FOXO3. Overall, observed treatment-specific effects including the upregulation of SIRT1 and downregulation of FOXO3 and p53. Finally, a GC/MS analysis of the fatty acid composition of animals' livers and the chows was performed in order to obtain an idea about the presence of specific compounds that may shape the effects of ketogenic diets on autophagy.

Substances of abuse and the blood brain barrier: Interactions with physical exercise.

Substance use disorders pose a common medical, social and financial problem. Among the pathomechanisms of substance use disorders, the disruption and increased permeability of the blood-brain barrier has been recently revealed. Physical exercise appears to be a relatively inexpensive and feasible way to implement behavioral therapy counteracting the blood-brain barrier impairment. Concomitantly, there are also studies supporting a potential protective role of selected substances of abuse in maintaining the blood-brain barrier integrity. In this review, we aim to provide a summary on the modulatory influence of physical exercise, a non-pharmacological intervention, on the blood-brain barrier alterations caused by substances of abuse. Further studies are needed to understand the precise mechanisms that underlie various effects of physical exercise in substance use disorders.

Reprogramming and transdifferentiation - two key processes for regenerative medicine.

Regenerative medicine based on transplants obtained from donors or foetal and new-born mesenchymal stem cells, encounter important obstacles such as limited availability of organs, ethical issues and immune rejection. The growing demand for therapeutic methods for patients being treated after serious accidents, severe organ dysfunction and an increasing number of cancer surgeries, exceeds the possibilities of the therapies that are currently available. Reprogramming and transdifferentiation provide powerful bioengineering tools. Both procedures are based on the somatic differentiated cells, which are easily and unlimitedly available, like for example: fibroblasts. During the reprogramming procedure mature cells are converted into pluripotent cells - which are capable to differentiate into almost any kind of desired cells. Transdifferentiation directly converts differentiated cells of one type into another differentiated cells type. Both procedures allow to obtained patient's dedicated cells for therapeutic purpose in regenerative medicine. In combination with biomaterials, it is possible to obtain even whole anatomical structures. Those patient's dedicated structures may serve for them upon serious accidents with massive tissue damage but also upon cancer surgeries as a replacement of damaged organ. Detailed information about reprogramming and transdifferentiation procedures as well as the current state of the art are presented in our review.

What Determines Spontaneous Physical Activity in Patients with Parkinson's Disease?

Physical activity (PA) is a factor that may have an influence on the symptoms of Parkinson's disease (PD). The aim of this study was to identify the potential determinants of spontaneous PA in a PD patient group. A total of 134 PD patients aged 65.2 ± 9.2 years with a Hoehn-Yahr scale score ≤4 and a Mini Mental State Examination (MMSE) score ≥24 were examined. For the study's purposes, the authors analyzed age, sex, education, history of PD, dopaminergic treatment, the severity of PD symptoms using Unified Parkinson's Disease Rating Scale (UPDRS), and Hoehn-Yahr scale. Additionally, all participants were evaluated through a set of scales for specific neuropsychiatric symptoms including depression, anxiety, apathy, fatigue, and sleep disorders. A linear regression analysis was used with backward elimination. In the total explanatory model, for 12% of the variability in activity (R2 = 0.125; F(16.133) = 2.185; p < 0.01), the significant predictor was starting therapy with the dopamine agonist (DA) (ß= 0.420; t= 4.068; p = 0.000), which was associated with a longer duration of moderate PA. In the total explanatory model, for more than 13% of the variance in time spent sitting (R2 = 0.135; F(16.130) = 2.267; p < 0.01), the significant predictors were secondary education and the results of the UPDRS. The patients with secondary and vocational education, those starting treatment with DA and those with a less severe degree of Parkinson's symptoms (UPDRS), spent less time sitting in a day. It is possible to identify determinants of spontaneous PA. It may elucidate consequences in terms of influence on modifiable conditions of PA and the proper approach to patients with unmodifiable PA factors.

Physical activity reduces anxiety and regulates brain fatty acid synthesis.

Physical activity impacts brain functions, but the direct mechanisms of this effect are not fully recognized or understood. Among multidimensional changes induced by physical activity, brain fatty acids (FA) appear to play an important role; however, the knowledge in this area is particularly scarce. Here we performed global metabolomics profiling of the hippocampus and the frontal cortex (FC) in a model of voluntary running in mice. Examined brain structures responded differentially to physical activity. Specifically, the markers of the tricarboxylic acid (TCA) cycle were downregulated in the FC, whereas glycolysis was enhanced in the hippocampus. Physical activity stimulated production of myristic, palmitic and stearic FA; i.e., the primary end products of de novo lipogenesis in the brain, which was accompanied by increased expression of hippocampal fatty acid synthase (FASN), suggesting stimulation of lipid synthesis. The changes in the brain fatty acid profile were associated with reduced anxiety level in the running mice. Overall, the study examines exercise-related metabolic changes in the brain and links them to behavioral outcomes.

Correction: Association of PDCD6 polymorphisms with the risk of cancer: Evidence from a meta-analysis.

[This corrects the article DOI: 10.18632/oncotarget.25324.].

Correction to: Human Gyrovirus-Apoptin Interferes with the Cell Cycle and Induces G2/M Arrest Prior to Apoptosis.

The authors would like to correct the following error.

Pressure Injuries Treated With Anodal and Cathodal High-voltage Electrical Stimulation: the Effect on Blood Serum Concentration of Cytokines and Growth Factors in Patients With Neurological Injuries. A Randomized Clinical Study.

It remains unclear whether electrical currents can affect biological factors that determine chronic wound healing in humans. PURPOSE: The aim of this study was to determine whether anodal and cathodal high-voltage monophasic pulsed currents (HVMPC) provided to the area of a pressure injury (PI) change the blood level of cytokines (interleukin [IL]-1ß, IL-10, and tumor necrosis factor [TNF]-α) and growth factors (insulin-like growth factor [IGF]-1 and transforming growth factor [TGF]-ß1) in patients with neurological injuries and whether the level of circulatory cytokines and growth factors correlates with PI healing progression. METHODS: This study was part of a randomized clinical trial on the effects of HVMPC on PI healing. All patients with neurological injuries (spinal cord injury, ischemic stroke, and blunt trauma to the head) and a stage 2, stage 3, or stage 4 PI of at least 4 weeks' duration hospitalized in one rehabilitation center were eligible to participate if older than 18 years of age and willing to consent to donating blood samples. Exclusion criteria included local contraindications to electrical stimulation (cancer, electronic implants, osteomyelitis, tunneling, necrotic wounds), PIs requiring surgical intervention, patients with poorly controlled diabetes mellitus (HbA1C > 7%), critical wound infection, and/or allergies to standard wound treatment. Participants were randomly assigned to 1 of 3 groups: anodal (AG) or cathodal (CG) HVMPC treatment (154 µs; 100 Hz; 360 µC/sec; 1.08 C/day) or a placebo (PG, sham) applied for 50 minutes a day, 5 days per week, for 8 weeks. TNF-α, IL-1ß, IL-10, TGF-ß1, and IGF-1 levels in blood serum were assessed using the immunoenzyme method (ELISA) and by chemiluminescence, respectively, at baseline and week 4. Wound surface area measurements were obtained at baseline and week 4 and analyzed using a digitizer connected to a personal computer. Statistical analyses were performed using the maximum-likelihood chi-squared test, the analysis of variance Kruskal-Wallis test, the Kruskal-Wallis post-hoc test, and Spearman's rank order correlation; the level of significance was set at P ≤.05. RESULTS: Among the 43 participants, 15 were randomized to AG (mean age 53.87 ± 13.30 years), 13 to CG (mean age 51.08 ± 20.43 years), and 15 to PG treatment (mean age 51.20 ± 14.47 years). Most PIs were located in the sacral region (12, 74.42%) and were stage 3 (11, 67.44%). Wound surface area baseline size ranged from 1.00 cm2 to 58.04 cm2. At baseline, none of the variables were significantly different. After 4 weeks, the concentration of IL-10 decreased in all groups (AG: 9.8%, CG: 38.54%, PG: 27.42%), but the decrease was smaller in the AG than CG group (P = .0046). The ratio of pro-inflammatory IL-10 to anti-inflammatory TNF-α increased 27.29% in the AG and decreased 26.79% in the CG and 18.56% in the PG groups. Differences between AG and CG and AG and PG were significant (AG compared to CG, P = .0009; AG compared to PG, P = .0054). Other percentage changes in cytokine and growth factor concentration were not statistically significant between groups. In the AG, the decrease of TNF-α and IL-1ß concentrations correlated positively with the decrease of PI size (P <.05). CONCLUSION: Anodal HVMPC elevates IL-10/TNF-α in blood serum. The decrease of TNF-α and IL-1ß concentrations in blood serum correlates with a decrease of PI wound area. More research is needed to determine whether the changes induced by anodal HVMPC improve PI healing and to determine whether and how different electrical currents affect the activity of biological agents responsible for specific wound healing phases, both within wounds and in patients' blood. In clinical practice, anodal HVMPC should be used to increase the ratio of anti-inflammatory IL-10 to pro-inflammatory TNF-α , which may promote healing.