The impact of early-life exercise on CREB-signaling pathway and hippocampus neuroplasticity in diabetic adult male rats; the study of developmental model.

BACKGROUND: Childhood exercise enhances brain structure, while diabetes detrimentally affects it. This study examines early-life exercise's influence on adult diabetic rats' memory and neuroplasticity. METHODS: Male Wistar pups were divided into Control, Diabetes, Exercise Training, and Diabetes exercise groups. Diabetes was induced on day 23 with Alloxan (200 mg/kg). A 3-week regimen included aerobic and resistance training thrice weekly. The aerobic intensity was 70%, and resistance varied from 50% to 100% of the maximal carrying capacity (MCC). Following the last training sessions, spatial memory and retrieval tests were performed in infancy, childhood, and emerging adulthood using the Morris Water Maze test (MWM). The hippocampus was excised to measure protein and gene expression of brain-derived neurotrophic factor (BDNF), calmodulin-dependent protein kinase (CAMKII), N-methyl-D-aspartate receptors (NMDAR), and cAMP-response element-binding protein (CREB) by western blotting and reverse transcription-polymerase-chain reaction (RT-PCR) methods. Blood samples were collected during each developmental stage to measure glucose levels, at the study's conclusion, to assess Interleukin-1ß levels using the ELISA method. The Nissel staining assessed dead hippocampal cells in CA1. RESULTS: Post-natal exercise improved spatial memory (p < 0.05) and glucose levels (p < 0.05) in diabetic rats during adolescence and emerging adulthood. Despite reduced mRNA expression (NMDAR 40%, BDNF 62%, CREB 43%, CAMKII 66%), diabetic rats, by study end, showed increased BDNF, NMDARR, CAMKII, CREB protein/gene expression (p < 0.05) in emerging adulthood for both training groups. CONCLUSION: Early-life exercise influenced hippocampal BDNF/NMDAR-CAMKII/CREB pathways in a diabetic rat model, highlighting post-natal exercise's role in neuroplasticity memory enhancement and improved glucose level.

Design and Validation of Miniaturized Repetitive Transcranial Magnetic Stimulation (rTMS) Head Coils.

Repetitive transcranial magnetic stimulation (rTMS) is a rapidly developing therapeutic modality for the safe and effective treatment of neuropsychiatric disorders. However, clinical rTMS driving systems and head coils are large, heavy, and expensive, so miniaturized, affordable rTMS devices may facilitate treatment access for patients at home, in underserved areas, in field and mobile hospitals, on ships and submarines, and in space. The central component of a portable rTMS system is a miniaturized, lightweight coil. Such a coil, when mated to lightweight driving circuits, must be able to induce B and E fields of sufficient intensity for medical use. This paper newly identifies and validates salient theoretical considerations specific to the dimensional scaling and miniaturization of coil geometries, particularly figure-8 coils, and delineates novel, key design criteria. In this context, the essential requirement of matching coil inductance with the characteristic resistance of the driver switches is highlighted. Computer simulations predicted E- and B-fields which were validated via benchtop experiments. Using a miniaturized coil with dimensions of 76 mm × 38 mm and weighing only 12.6 g, the peak E-field was 87 V/m at a distance of 1.5 cm. Practical considerations limited the maximum voltage and current to 350 V and 3.1 kA, respectively; nonetheless, this peak E-field value was well within the intensity range, 60-120 V/m, generally held to be therapeutically relevant. The presented parameters and results delineate coil and circuit guidelines for a future miniaturized, power-scalable rTMS system able to generate pulsed E-fields of sufficient amplitude for potential clinical use.

The effect of curcumin supplementation on circulating adiponectin and leptin concentration in adults: a GRADE-assessed systematic review and meta-analysis of randomised controlled trials.

Curcumin is a phytocompound found in the root of turmeric, a common herbal ingredient in many Asian cuisines. The compound contains anti-inflammatory activity, which is mediated through an upregulation of adiponectin and reduction of leptin. Results of randomised controlled trials (RCT) have shown that the effects of curcumin on adipokines are conflicting. Therefore, the current systematic review and meta-analysis of RCT were conducted with the aim of elucidating the role of curcumin supplementation on serum adiponectin and leptin. The search included PubMed, Embase, Cochrane Library, Scopus, Web of Science and Google Scholar from inception to August 2023. For net changes in adipokines, standardised mean differences (SMD) were calculated using random effects models. Thirteen RCT with fourteen treatment arms were eligible for inclusion in this meta-analysis. Curcumin supplementation was effective in increasing serum adiponectin (SMD = 0·86, 95 % CI (0·33, 1·39), P < 0·001; I2 = 93·1 %, P < 0·001) and reducing serum leptin (SMD = -1·42, 95 % CI (-2·29, -0·54), P < 0·001; I2 = 94·7 %, P < 0·001). In conclusion, curcumin supplementation significantly increased circulating adiponectin and decreased leptin levels in adults.

Periodontal Disease in Patients with Newly Diagnosed Systemic Lupus Erythematosus.

Statement of the Problem: Most of the studies assessing the relationship between systemic lupus erythematosus (SLE) and periodontal disorder are focused on patients with previously diagnosed SLE whose periodontal hygiene may be influenced by immunosuppressive therapies. Purpose: This study aimed to evaluate the frequency of periodontal disease among patients with newly diagnosed lupus before starting immunosuppressive therapy and its association with presenting laboratory and clinical symptoms of lupus. Materials and Method: This case-control cross-sectional study was conducted on 36 consecutive newly diagnosed SLE patients before starting any treatment. The control group consisted of first-degree relatives of the patients whose demographic and social characteristics matched with the patients and who had no personal history of a disease. Periodontal indices included community periodontal index (CPI) and plaque index (PI). Results: Participants in both groups had some degree of periodontal disorder. The mean value of CPI was 1.47±0.82 and 1.31±0.72 in SLE patients and healthy subjects (P=0.84), respectively. Moreover, the mean values of PI were 1.15±0.55 and 1.17±0.46 in SLE patients and controls, (P=0.37), respectively. Besides, the frequency of periodontal disorders based on CPI score (positive: higher than two) was 22.2% in SLE patients and 16.7% in controls (P=0.55). Moreover, there was no association between periodontal disease and lupus-related clinical and laboratory characteristics in our patients. Conclusion: The frequency of periodontal disorders is similar between newly diagnosed lupus patients without undergoing immunomodulatory therapies and healthy controls with the same demographic and social characteristics. Moreover, periodontitis was not associated with clinical and laboratory symptoms of our patients.

Can flaxseed supplementation affect circulating adipokines in adults? An updated systematic review and meta-analysis of randomized controlled trials.

Introduction: The findings of randomized controlled trials (RCTs) regarding the effect of flaxseed on adipokine concentrations are conflicting. Therefore, the present meta-analysis was conducted to provide definite and conclusive results. Methods: Systematically, Scopus, Embase, PubMed, Web of Science databases, and Google Scholar were searched for relevant literature published up to December 2022. Based on random-effect models, standard mean differences (SMDs) were calculated for net changes in adipokine concentrations. Results: Overall, 13 RCTs (15 arms) were eligible to be included. The results indicated that leptin was significantly reduced after the intervention with flaxseed supplement (SMD = -0.69, 95% CI: -1.37, -0.01; p = 0.048; I2 = 92.0%, p < 0.001). In addition, flaxseed supplements had no considerable effect on plasma adiponectin (SMD = 0.52, 95% CI: -0.20, 1.25, p = 0.159; I2 = 92.0%, p < 0.001). Discussion: Flaxseed significantly improves leptin but does not affect adiponectin concentrations. Additional future well-designed trials are required to further assess the potential benefits of flaxseed on adipokines in humans.

The effects of purslane (Portulaca oleracea) on glycemic indices: A GRADE-assessed systematic review and meta-analysis of randomized controlled trials.

Although several studies have revealed the benefits of purslane on glycemic indices, the results of some studies reject such effect. Therefore, aim of this meta-analysis of randomized controlled trials (RCTs) was to assess the effects of purslane supplementation on glycemic indices. Scientific international databases as Scopus, Web of Sciences, PubMed, Embase, and the Cochrane library were searched up to December 2022. For net changes in glycemic indices, weighted mean differences (WMDs) were calculated using random-effects models. Purslane supplementation had a statistically significant reduction in fasting blood glucose [FBG, WMD: -6.37; 95% CI: -9.34, -3.40, p < 0.001]. In addition, purslane did not significant effect on serum levels of insulin [WMD: -0.74; 95% CI: -2.58, 1.10; p = 0.430], homeostasis model assessment for insulin resistance [HOMA-IR, WMD: -0.25; 95% CI: -0.88, 0.37, p = 0.429], and QUICKI [WMD: -0.01; 95% CI: -0.01, 0.03, p = 0.317] compared with the control group. The results of our meta-analysis revealed a beneficial effect of purslane supplementation as a tool to decrease FBG levels, but not to HOMA-IR, insulin, and QUICKI levels. However, future high-quality, long-term clinical trials are needed to confirm our results.

Personalized repetitive transcranial magnetic stimulation (prtms®) for post-traumatic stress disorder (ptsd) in military combat veterans.

Emerging data suggest that post-traumatic stress disorder (PTSD) arises from disrupted brain default mode network (DMN) activity manifested by dysregulated encephalogram (EEG) alpha oscillations. Hence, we pursued the treatment of combat veterans with PTSD (n = 185) using an expanded form of repetitive transcranial magnetic stimulation (rTMS) termed personalized-rTMS (PrTMS). In this treatment methodology spectral EEG based guidance is used to iteratively optimize symptom resolution via (1) stimulation of multiple motor sensory and frontal cortical sites at reduced power, and (2) adjustments of cortical treatment loci and stimulus frequency during treatment progression based on a proprietary frequency algorithm (PeakLogic, Inc. San Diego) identifying stimulation frequency in the DMN elements of the alpha oscillatory band. Following 4 - 6 weeks of PrTMS® therapy in addition to routine PTSD therapy, veterans exhibited significant clinical improvement accompanied by increased cortical alpha center frequency and alpha oscillatory synchronization. Full resolution of PTSD symptoms was attained in over 50% of patients. These data support DMN involvement in PTSD pathophysiology and suggest a role in therapeutic outcomes. Prospective, sham controlled PrTMS® trials may be warranted to validate our clinical findings and to examine the contribution of DMN targeting for novel preventive, diagnostic, and therapeutic strategies tailored to the unique needs of individual patients with both combat and non-combat PTSD.

Effects of exercise on immune cells with tumor-specific activity in breast cancer patients and survivors: a systematic review and meta-analysis.

Exercise is effective for improving the physical and psychological health of breast cancer patients. However, there is still controversy around its role on the immune system. Therefore, this systematic review and meta-analysis is aimed to evaluate the effect of chronic exercise on the number and activity of the immune cells that can contribute to anti-tumor immune responses, such as natural killers (NK) cells, CD + 4, or CD + 8. The main hypothesis of this study was that exercise could improve the immune system or, at least, there will not be a reduction in the number or activity of immune cells because of exercise. The search was conducted in the PubMed and Web of Science databases. Out of 244 studies reviewed, 10 studies met the inclusion criteria. The studies included in the meta-analyses showed mixed results and no significant (p > 0.05) positive or negative effects of exercise interventions in women with breast cancer. Therefore, the current evidence indicates that exercise does not significantly improve or reduce the immune system; thus, the prescription of exercise must not be discouraged due to the effects on the number and activity of immune system cells, but should be recommended due to the well-known benefits in quality of life, physical function or fatigue, and the absence of negative effects on the immune system. Further studies are needed to evaluate the effects according to the type of exercise, the type of cancer, or the timing of the intervention.

The Potential of Exerkines in Women's COVID-19: A New Idea for a Better and More Accurate Understanding of the Mechanisms behind Physical Exercise.

The benefits of physical exercise are well-known, but there are still many questions regarding COVID-19. Chow et al.'s 2022 study, titled Exerkines and Disease, showed that a special focus on exerkines can help to better understand the underlying mechanisms of physical exercise and disease. Exerkines are a group of promising molecules that may underlie the beneficial effects of physical exercise in diseases. The idea of exerkines is to understand the effects of physical exercise on diseases better. Exerkines have a high potential for the treatment of diseases and, considering that, there is still no study of the importance of exerkines on the most dangerous disease in the world in recent years, COVID-19. This raises the fundamental question of whether exerkines have the potential to manage COVID-19. Most of the studies focused on the general changes in physical exercise in patients with COVID-19, both during the illness and after discharge from the hospital, and did not investigate the basic differences. A unique look at the management of COVID-19 by exerkines, especially in obese and overweight women who experience high severity of COVID-19 and whose recovery period is long after discharge from the hospital, can help to understand the basic mechanisms. In this review, we explore the potential of exerkines in COVID-19 by practicing physical exercise to provide compelling practice recommendations with new insights.

A Compact Circuit for Boosting Electric Field Intensity in Repetitive Transcranial Magnetic Stimulation (rTMS).

The concept of a portable, wearable system for repetitive transcranial stimulation (rTMS) has attracted widespread attention, but significant power and field intensity requirements remain a key challenge. Here, a circuit topology is described that significantly increases induced electric field intensity over that attainable with similar current levels and coils in conventional rTMS systems. The resultant electric field is essentially monophasic, and has a controllable, shortened duration. The system is demonstrated in a compact circuit implementation for which an electric field of 94 V/m at a depth of 2 cm is measured (147 V/m at 1 cm depth) with a power supply voltage of 80 V, a maximum current of 500 A, and an effective pulse duration (half amplitude width) of 7 µsec. The peak electric field is on the same order as that of commercially available systems at full power and comparable depths. An electric field boost of 5x is demonstrated in comparison with our system operated conventionally, employing a 70 µsec rise time. It is shown that the power requirements for rTMS systems depend on the square of the product of electric field Ep and pulse duration tp, and that the proposed circuit technique enables continuous variation and optimization of the tradeoff between Ep and tp. It is shown that the electric field induced in a medium such as the human brain cortex at a specific depth is proportional to the voltage generated in a given loop of the generating coil, which allows insights into techniques for its optimization. This rTMS electric field enhancement strategy, termed 'boost rTMS (rbTMS)' is expected to increase the effectiveness of neural stimulation, and allow greater flexibility in the design of portable rTMS power systems.Clinical Relevance- This study aims to facilitate a compact, battery-powered rTMS prototype with enhanced electric field which will permit broader and more convenient rTMS treatment at home, in a small clinic, vessel, or field hospital, and potentially, on an ambulatory basis.

A double-blind placebo-controlled randomized trial of oral saffron in the treatment of rheumatoid arthritis.

OBJECTIVE: Recently, saffron (Crocus sativus L. from the Iridaceae family) has been characterized by its antioxidant, anti-inflammatory and analgesic effects. This study aimed to evaluate the effect of saffron on disease activity in patients with rheumatoid arthritis (RA). MATERIALS AND METHODS: This is a double-blind, placebo-controlled, randomized clinical trial (RCT) performed on 55 newly- diagnosed RA patients without previous treatment, who were randomly divided into intervention (included 28 cases) and control groups (consisted of 27 individuals). Standard therapy including prednisolone, oral methotrexate, folic acid, vitamin D, calcium, and alendronate, was administered similarly in both groups. Patients received a 100 mg saffron pill/day (pure saffron powder) or placebo besides the standard protocol. The placebo had the same shape as the saffron pills. Follow up of DAS28ESR disease activity score was done on the 30th, 45th and 90th day of the study. RESULTS: There was no difference between the intervention and control groups regarding to the DAS28ESR at the end of the study. However, a significant decrease in DAS28-ESR was observed in each group compared to the first visit (p=0.001). The results also showed no significant difference in the incidence of side effects in both groups. CONCLUSION: In summary, patients who received pure saffron pills (100 mg/day) in addition to standard therapy did not have a significant difference in improvement of disease activity from the patients on standard therapy.

A Compact Battery-Powered rTMS Prototype.

This paper describes the design and testing of a compact, battery-powered repetitive Transcranial Magnetic Stimulation (rTMS) prototype. This device generates a 10 Hz magnetic pulse train with peak flux density of 100 mT at 2 cm distance. Circuit component design, including the inductor, switched LC resonator, and boost converter, are discussed in the context of weight and size reduction, and performance optimization. The experimental approach and rationale together with acquired results validating the rTMS prototype design are presented. To the best of our knowledge, this is the first comprehensive feasibility demonstration of an inexpensive, lightweight, and portable rTMS device able to generate therapeutic levels of current, pulse rise time, and number of pulses. The generated magnetic field was kept to 0.1 Tesla for safety and testing considerations, but nevertheless was very close to therapeutic intensity, with driving circuitry scalable to support much stronger fields.Clinical Relevance- This feasibility study of a compact, battery-powered rTMS prototype test platform aims to enable broader and more convenient rTMS treatment at home, in a small clinic, vessel, or field hospital, and potentially, on an ambulatory basis.

Electrodeposition modeling and optimization to improve thin film patterning with orchestrated structure evolution.

Orchestrated structure evolution is an alternative nanomanufacturing approach that combines the advantages of top-down patterning and bottom-up self-organizing growth. It relies upon tool-directed patterning to create 'seed' locations on a surface from which a subsequent deposition process produces the final, merged film. Despite its demonstrated ability to reduce patterning time by orders of magnitude, our prior reliance on mass transfer limited deposition and square seed arrays resulted in extraneous film growth along pattern edges, thereby limiting the pattern quality of the final film. Here, quality improvements are demonstrated by modeling and tuning the growth mechanism of the deposition step to include charge transfer effects. In addition, a seed positioning optimization technique derived from simulated annealing is introduced as a method for relocating the seeds to minimize film overgrowth at the pattern edges. These improvements enable OSE to maintain geometric quality while substantially reducing the time and cost compared to traditional direct-write manufacturing methods.

Orchestrated structure evolution: modeling growth-regulated nanomanufacturing.

Orchestrated structure evolution (OSE) is a scalable manufacturing method that combines the advantages of top-down (tool-directed) and bottom-up (self-propagating) approaches. The method consists of a seed patterning step that defines where material nucleates, followed by a growth step that merges seeded islands into the final patterned thin film. We develop a model to predict the completed pattern based on a computationally efficient approximate Green's function solution of the diffusion equation plus a Voronoi diagram based approach that defines the final grain boundary structure. Experimental results rely on electron beam lithography to pattern the seeds, followed by the mass transfer limited growth of copper via electrodeposition. The seed growth model is compared with experimental results to quantify nearest neighbor seed-to-seed interactions as well as how seeds interact with the pattern boundary to impact the local growth rate. Seed-to-seed and seed-to-pattern interactions are shown to result in overgrowth of seeds on edges and corners of the shape, where seeds have fewer neighbors. We explore how local changes to the seed location can be used to improve the patterning quality without increasing the manufacturing cost. OSE is shown to enable a unique set of trade-offs between the cost, time, and quality of thin film patterning.