GDP-mannose pyrophosphorylase is an efficient target in Xanthomonas citri for citrus canker control.

Xanthomonas citri subsp. citri (Xcc) is a bacterium that causes citrus canker, an economically important disease that results in premature fruit drop and reduced yield of fresh fruit. In this study, we demonstrated the involvement of XanB, an enzyme with phosphomannose isomerase (PMI) and guanosine diphosphate-mannose pyrophosphorylase (GMP) activities, in Xcc pathogenicity. Additionally, we found that XanB inhibitors protect the host against Xcc infection. Besides being deficient in motility, biofilm production, and ultraviolet resistance, the xanB deletion mutant was unable to cause disease, whereas xanB complementation restored wild-type phenotypes. XanB homology modeling allowed in silico virtual screening of inhibitors from databases, three of them being suitable in terms of absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) properties, which inhibited GMP (but not PMI) activity of the Xcc recombinant XanB protein in more than 50%. Inhibitors reduced citrus canker severity up to 95%, similarly to copper-based treatment. xanB is essential for Xcc pathogenicity, and XanB inhibitors can be used for the citrus canker control. IMPORTANCE: Xcc causes citrus canker, a threat to citrus production, which has been managed with copper, being required a more sustainable alternative for the disease control. XanB was previously found on the surface of Xcc, interacting with the host and displaying PMI and GMP activities. We demonstrated by xanB deletion and complementation that GMP activity plays a critical role in Xcc pathogenicity, particularly in biofilm formation. XanB homology modeling was performed, and in silico virtual screening led to carbohydrate-derived compounds able to inhibit XanB activity and reduce disease symptoms by 95%. XanB emerges as a promising target for drug design for control of citrus canker and other economically important diseases caused by Xanthomonas sp.

Determination of resistance at zero and infinite frequencies in bioimpedance spectroscopy for assessment of body composition in babies.

Objective. Bioimpedance spectroscopy (BIS) is a popular technique for the assessment of body composition in children and adults but has not found extensive use in babies and infants. This due primarily to technical difficulties of measurement in these groups. Although improvements in data modelling have, in part, mitigated this issue, the problem continues to yield unacceptably high rates of poor quality data. This study investigated an alternative data modelling procedure obviating issues associated with BIS measurements in babies and infants.Approach.BIS data are conventionally analysed according to the Cole model describing the impedance response of body tissues to an appliedACcurrent. This approach is susceptible to errors due to capacitive leakage errors of measurement at high frequency. The alternative is to model BIS data based on the resistance-frequency spectrum rather than the reactance-resistance Cole model thereby avoiding capacitive error impacts upon reactance measurements.Main results.The resistance-frequency approach allowed analysis of 100% of data files obtained from BIS measurements in 72 babies compared to 87% successful analyses with the Cole model. Resistance-frequency modelling error (percentage standard error of the estimate) was half that of the Cole method. Estimated resistances at zero and infinite frequency were used to predict body composition. Resistance-based prediction of fat-free mass (FFM) exhibited a 30% improvement in the two-standard deviation limits of agreement with reference FFM measured by air displacement plethysmography when compared to Cole model-based predictions.Significance.This study has demonstrated improvement in the analysis of BIS data based on the resistance frequency response rather than conventional Cole modelling. This approach is recommended for use where BIS data are compromised by high frequency capacitive leakage errors such as those obtained in babies and infants.

Effects of amber LED on inflammatory and regulatory monocytes and lymphocytes.

The primary objective of the present study was to assess the impact of amber LED photobiomodulation (PBM) on human monocytes and lymphocytes that were polarized into proinflammatory and regulatory/reparative phenotypes. Human leukocytes were polarized with LPS or LPS + IL-4 for 2 h and irradiated after 2 and 6 h with amber LED (590 nm). Cell absorbance spectrum and gene and protein expression of IL-1ß, IL-6, IL-10, IL-17, TNF-α and IFNγ determined after 24 h. The results showed that irradiation did not significantly alter absorbance of non-polarized monocytes, whereas irradiated polarized monocytes presented reduction in absorbance in 625-850 nm region. Irradiated monocytes polarized with LPS + IL-4 presented reduction in absorbance in 600-725 nm region compared to non-irradiated group. Irradiated non-polarized lymphocytes presented absorbance peaks between 650 and 820 nm not seen in non-irradiated group. No difference was found in absorbance pattern of polarized lymphocytes after irradiation. Irradiation led to reduction in protein synthesis of IL-6 and TNFα in monocytes polarized to proinflammatory phenotype and increase in production of IL-17 in lymphocytes. Irradiation reduced production of IL-10 in monocytes and lymphocytes polarized to immunoregulatory phenotype. In conclusion, amber LED modulates light absorbance and expression of important cytokines in inflammatory/repair processes in monocytes and lymphocytes.

An Intestinal FXR Agonist Mitigates Dysbiosis, Intestinal Tight Junctions, and Inflammation in High-Fat Diet-Fed Mice.

SCOPE: To analyze the effects of fexaramine (FEX), as an intestinal FXR agonist, on the modulation of the intestinal microbiota and ileum of mice fed a high-fat (HF) diet. METHODS AND RESULTS: Three-month-old C57Bl/6 male mice are divided into two groups and received a control (C, 10% of energy from lipids) or HF (50% of energy from lipids) diet for 12 weeks. They are subdivided into the C, C + FEX, HF, and HF + FEX groups. FEX is administered (FEX-5 mg kg-1 ) via orogastric gavage for three weeks. Body mass (BM), glucose metabolism, qPCR 16S rRNA gene expression, and ileum gene expression, bile acids (BAs), tight junctions (TJs), and incretin are analyzed. FEX reduces BM and glucose intolerance, reduces plasma lipid concentrations and the Firmicutes/Bacteroidetes ratio, increases the Lactobacillus sp. and Prevotella sp. abundance, and reduces the Escherichia coli abundance. Consequently, the ileal gene expression of Fxr-Fgf15, Tgr5-Glp1, and Cldn-Ocldn-Zo1 is increased, and Tlr4-Il6-Il1beta is decreased. CONCLUSION: FEX stimulates intestinal FXR and improves dysbiosis, intestinal TJs, and the release of incretins, mitigating glucose intolerance and BM increases induced by an HF diet. However, FEX results in glucose intolerance, insulin resistance, and reduces intestinal TJs in a control group, thus demonstrating limitations to this dietary model.

Lysicamine Reduces Protein Kinase B (AKT) Activation and Promotes Necrosis in Anaplastic Thyroid Cancer.

Anaplastic thyroid cancer (ATC) is an aggressive form of thyroid cancer (TC), accounting for 50% of total TC-related deaths. Although therapeutic approaches against TC have improved in recent years, the survival rate remains low, and severe adverse effects are commonly reported. However, unexplored alternatives based on natural compounds, such as lysicamine, an alkaloid found in plants with established cytotoxicity against breast and liver cancers, offer promise. Therefore, this study aimed to explore the antineoplastic effects of lysicamine in papillary TC (BCPAP) and ATC (HTH83 and KTC-2) cells. Lysicamine treatment reduced cell viability, motility, colony formation, and AKT activation while increasing the percentage of necrotic cells. The absence of caspase activity confirmed apoptosis-independent cell death. Necrostatin-1 (NEC-1)-mediated necrosome inhibition reduced lysicamine-induced necrosis in KTC-2, suggesting necroptosis induction via a reactive oxygen species (ROS)-independent mechanism. Additionally, in silico analysis predicted lysicamine target proteins, particularly those related to MAPK and TGF-ß signaling. Our study demonstrated lysicamine's potential as an antineoplastic compound in ATC cells with a proposed mechanism related to inhibiting AKT activation and inducing cell death.

Umbilical cord mesenchymal stromal cell-derived extracellular vesicles lack the potency to immunomodulate human monocyte-derived macrophages in vitro.

Mesenchymal stromal cells (MSCs) have been reported to display efficacy in a variety of preclinical models, but without long-term engraftment, suggesting a role for secreted factors, such as MSC-derived extracellular vesicles (EVs). MSCs are known to elicit immunomodulatory effects, an important aspect of which is their ability to affect macrophage phenotype. However, it is not clear if these effects are mediated by MSC-derived EVs, or other factors secreted by the MSCs. Here, we use flow cytometry to assess the effects of human umbilical cord (hUC) MSC-derived EVs on the expression of pro-inflammatory (CD80) and anti-inflammatory (CD163) surface markers in human monocyte-derived macrophages (hMDMs). hUC-MSC-derived EVs did not change the surface marker expression of the hMDMs. In contrast, when hMDMs were co-incubated with hUC-MSCs in indirect co-cultures, changes were observed in the expression of CD14, CD80 and CD163, particularly in M1 macrophages, suggesting that soluble factors are necessary to elicit a shift in phenotype. However, even though EVs did not alter the surface marker expression of macrophages, they promoted angiogenesis and phagocytic capacity increased proportionally to increases in EV concentration. Taken together, these results suggest that hUC-MSC-derived EVs are not sufficient to alter macrophage phenotype and that additional MSC-derived factors are needed.

Application of Photodynamic Therapy in Pediatric Dentistry: Literature Review.

Microbiological control of dental pathologies presents a significant clinical challenge for dental surgeons, particularly considering drug-resistant microorganisms. To address this issue, Antimicrobial Photodynamic Therapy (PDT) has emerged as an effective and complementary technique for microbial reduction. This therapy involves the application of a photosensitizer dye (PS) either topically or systemically, followed by exposure to low-power lasers with appropriate visible light wavelengths. PDT has found a valuable place in dentistry across various specialties, including surgery, periodontics, endodontics, dentistry, implantology, orthodontics, and pediatrics. In the realm of pediatric dentistry, managing microorganisms during dental treatments has become a major challenge. Considering its promising results and ease of application, Photodynamic Therapy presents an interesting alternative for clinical practice. However, it is important to note that specific protocols must be followed for each application, encompassing the type of photosensitizer, concentration, pre-irradiation time, light type, wavelength, energy, power, and mode of light delivery. Researchers have been steadily refining these protocols to facilitate PDT's integration into clinical practice. The objective of this review is to describe in which procedures and oral health problems in children PDT can be applied. In this sense, we list what the literature brings about the possibilities of applying PDT in a pediatric dentistry clinic.

Photobiomodulation increases uprighting tooth movement and modulates IL-1ß expression during orthodontically bone remodeling.

This study investigated the effects of photobiomodulation (PBM) in acceleration of orthodontic movement of inferior molar uprighting movement. Thirty-four individuals, with indication of molar uprighting movement for oral rehabilitation, were randomly divided in two groups: verticalization + PBM (808 nm, 100 mW, 1 J per point, 10 points and 25 J/cm2 ) or verticalization + PBM simulation. Elastomeric chain ligatures were changed every 30 days for 3 months. FBM was performed immediately, 24 h, 72 h, 1 and 2 months after activation. The primary outcome was the amount of uprighting movement. Secondary outcomes were pain, amount of medication, OHIP-14 questionnaire, and cytokine IL-1ß. PBM group increase uprighting movement when compared to control after 3 months and modulate IL-1ß expression. For pain control, the amount of medication and OHIP-14 no difference were found. This study suggests that PBM accelerates tooth movement during molar uprighting, due to modulation of IL-1ß during bone remodeling.

Effect of Photobiomodulation Combined with Physiotherapy on Functional Performance in Children with Myelomeningo-Cele-Randomized, Blind, Clinical Trial.

BACKGROUND: This study aimed to evaluate the electrical activity of the rectus femoris, tibialis anterior, and lateral gastrocnemius muscles during the sit-to-stand task and functional mobility after a neurofunctional physiotherapy protocol associated with PBM. METHODS: Twenty-five children were randomly allocated to either Active PBM + physiotherapy (n = 13) or PBM sham + physiotherapy (n = 12). PBM was carried out with a LED device (850 nm, 25 J, 50 s per point and 200 mW) at four points over the area with absence of a spiny process. Both groups completed a twelve-week supervised program with two weekly 45-60 min sessions. Pre-training and post-training assessments involved the Pediatric Evaluation of Disability Inventory (PEDI). Muscle activity was assessed using portable electromyography (BTS Engineering) and the electrodes were positioned on the lateral gastrocnemius, anterior tibialis, and rectus femoris muscles. The RMS data were recorded and analyzed. RESULTS: After 24 sessions of the treatment protocol, improvements were found in the PEDI score. The participants presented greater independence in performing the tasks, requiring less assistance from their caregivers. More significant electrical activity was found in the three muscles evaluated between the rest period and execution of the sit-to-stand tasks, both in the more compromised or less compromised lower limbs. CONCLUSION: Neurofunctional physiotherapy with or without PBM improved functional mobility and electrical muscle activity in children with myelomeningocele.

Systemic vascular photobiomodulation accelerates the recovery of motor activity in rats following spinal cord injury.

OBJECTIVES: Spinal cord injury (SCI) causes the discontinuity of the spinal canal, leading to functional and sensorial losses in areas below the injury, which are often irreversible. Photobiomodulation (PBM) can enhance the neuromuscular repair process, especially in cases of peripheral nerve injuries. However, there is little knowledge regarding the effects of this therapeutic modality on recovery following a SCI, especially the noninvasive systemic form denominated vascular PBM (VPBM). To analyze the effects of VPBM in the immediate, acute and intermediate phases following a compression-induced SCI on morphological aspects of neuromuscular tissue repair, functional recovery and the protein expression of brain-derived neurotrophic factor (BDNF). METHODS: Wistar rats were divided into five groups: control, SCI, SCI + VPBM-Im (immediate administration of VPBM), SCI + VPBM-2h (VPBM administered 2 h after injury) and SCI + VPBM-14d (VPBM administered 14 days after injury). VPBM was administered in the region of the caudal vein/artery with low-level laser (AsGaAl, 780 nm, 80 J/cm², 40 mW for 80 s, totaling an energy of 3.2 J over a single point) for 14 consecutive days. During the analysis periods (1, 3, 7, 14, 21, 28 and 35 days after injury), functioning was evaluated using the Basso-Beattie-Bresnahan (BBB) index. At the end of each experimental period, blood samples were collected for the determination of the concentration of circulating BDNF using ELISA. Muscle tissue and nerve tissue samples were also extracted for morphological and histological analyses using H&E staining. RESULTS: SCI + VPBM-Im and SCI + VPBM-2 h led to the recovery of motor function beginning on the 7th day after injury (p < 0.05), an increase in the cross-sectional area (CSA) of the muscle fibers in the second week (p < 0.05) and an increase in muscle fiber diameter beginning on Day 14 (p < 0.05). Early irradiation had a greater effect on the reduction in the size of the cavity, with stabilization of the cavity found on Day 7 (p < 0.05). Considering the circulating BDNF levels, no changes was found during the experimental periods. CONCLUSION: The present results showed that VPBM was capable of modulating morphological and functional recovery following SCI, especially when administered early. The positive effects on functional recovery were demonstrated by the BBB index; the reestablishment of the structure of the muscle and nerve tissue was demonstrated by the preservation of CSA and diameter of muscle fiber and reduction in the area of the injury (cavity size) respectively. Thus, noninvasive VPBM may be an important component of treatment for spinal cord injuries.

Photodynamic therapy with acai (Euterpe oleracea) and blue light in oral cells: A spectroscopic and cytotoxicity analysis.

OBJECTIVE: To evaluate the potential of photodynamic therapy (PDT) with blue light-emitting diode (LED) 460 nm at 25, 50 and 100 J/cm2 using three concentrations of acai extracts (100, 40, and 10 mg/ml), in the proliferation and viability of head and neck tumor lines (SCC9). METHODS: Three groups of cells were analyzed for 3 days in an in vitro assay with MTT (3- (4,5-dimethylthiazol-2-yl) -2,5, -diphenyltetrazolium bromide) and crystal violet: cells in the absence of acai extract and PDT (control group); cells in the presence of acai extract and no light; and cells in the presence of acai extract and LED blue light (PDT groups). RESULTS: When using acai as a PS combined with blue LED (460 nm, 0.7466 cm2 , 1000 mW/cm2 ) and irradiation at 25, 50, and 100 J/cm2 , after 72 h, cell viability (p < 0.0001 vs. control, p = 0.0027 vs. 100 mg/ml açai group, p = 0.0039 vs. 40 mg/ml açai group, p = 0.0135 vs. 10 mg/ml açai group; One-Way ANOVA/Tukey) and proliferation (p < 0.05, One-Way ANOVA/Tukey) decreased. CONCLUSION: The acai in question is a potential photosensitizer (PS), with blue light absorbance and efficacy against head and neck tumor lines (SCC9).

Unsaturation pattern of phosphatidylglycerols modulating the interaction of lysicamine with cells membrane models at the air-water interface.

Lysicamine, an alkaloid with tumorigenic activity, was incorporated in cell membrane models made of lipid Langmuir monolayers. Dipalmitoylphosphocholine (DPPC), dioleoylphosphocholine (DOPC), and palmitoyloleoylcholine (POPC) represented non-tumorigenic cell membranes, and dipalmitoylphosphoserine (DPPS), dioleoylphosphoserine (DOPS), and palmitoyloleoylserine (POPS), tumorigenic ones. The monolayers were characterized by tensiometry, infrared spectroscopy, and Brewster Angle Microscopy (BAM). No significant shifts of the isotherms were observed for the saturated lipids (DPPC and DPPS), while for the others (DOPC, POPS, DOPS, and POPS), more significant changes were observed not only in the compression isotherms but also in the surface pressure-time curve for pre-compressed monolayers. The molecular organization, as well as the morphology of the drug-lipid monolayers, could be inferred with infrared spectroscopy and BAM. While the first revealed that the alkyl chain ordering changed upon lysicamine incorporation, the second showed how the drug could distinctly change the state of aggregation of molecular domains at the air-water interface. In conclusion, lysicamine could interact distinctly with each lipid at the air-water interface, showing the dependence not only on the lipid polar groups but also on the level of unsaturation of the alkyl chains.

The composition of fusogenic lipid mixtures at the air-water modulates the physicochemical properties changes upon interaction with lysicamine.

Knowing how a bioactive compound interacts with cell membranes is important to understand its effect at the molecular level. In this sense, this work aimed to study the interaction of lysicamine, an alkaloid with action against lung cancer cell lines, with lipid monolayers as cell membrane models. We employed two lipid mixtures: the first composed of 35% DOPC, 30% DOPE, 20% sphingomyelin, and 15% cholesterol as healthy cell membranes models (MM1), and the second replacing DOPC with DOPS as cancer cells models (MM2). The interaction of lysicamine with the monolayers was evaluated using tensiometry, Brewster angle microscopy (BAM), and polarization-modulated infrared reflection-absorption spectroscopy (PM-IRRAS). Lysicamine had interfacial effects in both membrane models. For MM 1, it expanded the lipid monolayer and changed the interfacial rheological properties, increasing the in-plane elasticity of the films. PM-IRRAS spectra suggested a higher conformational disorder of the alkyl chains of the lipids. For MM 2, lysicamine also shifted the isotherms to higher areas, expanding the monolayers, but with no significant alteration in their interfacial rheological properties. PM-IRRAS spectra also suggested higher disorder in the orientation of the lipid alkyl chains upon lysicamine incorporation. For both models, BAM did not show alteration in interfacial aggregation upon drug incorporation. In conclusion, changes in some interfacial properties of membrane models caused by lysicamine depend on the monolayer composition, which can be associated with its bioactivity in cellular membranes.

Effects of systemic vascular photobiomodulation using LED or laser on sensory-motor recovery following a peripheral nerve injury in Wistar rats.

Peripheral nerve injury (PNI) is associated with considerable functional impairment. Photobiomodulation (PBM) has demonstrated positive effects regarding neuromuscular repair after PNI when applied locally to the nerve or injured muscle. However, the effects of systemic PBM with transcutaneous application over an important artery, which is also denominated vascular PBM (VPBM), remain unclear. The aim of the study was to compare the effects of VPBM with low-level laser (LLL) and light-emitting diode (LED) on gait, sensitivity and muscle morphology following a PNI. PNI was induced on Wistar rats using the sciatic nerve crushing technique. VPBM was performed over the rat's artery tail region with LED (850 nm, 40 mW, 3.2 J) and LLL (780 nm, 40 mW, 3.2 J). Gait functionality, mechanical (nociceptive) sensitivity, and morphology of the tibialis anterior muscle were evaluated at 7, 14, and 21 days after injury. An improvement in functional gait was shown in the VPBM-LLL group in all periods. Motor sensitivity was found after 14 days in the VPBM-LLL group. The left/right (L/R) muscle mass ratio revealed a reduction in muscle atrophy in the VPBM-LLL group at 7 days. Muscle fiber diameter increased in the VPBM-LED group at 14 days and increases in the cross-section area were found in the VPBM-LED and VPBM-LLL groups at 7 days. VPBM with both light sources (LED and LLL) positively modulated functioning and neuromuscular recovery following sciatic nerve injury in rats, with more pronounced results when using LLL.

Comparison of the Effects of High-Power Diode Laser and Electrocautery for Lingual Frenectomy in Infants: A Blinded Randomized Controlled Clinical Trial.

The aim of the study was to evaluate the release of the lingual frenulum through frenectomy in newborns zero to 90 days of age who breastfed and had diagnosis of ankyloglossia with an indication for surgery, comparing two methods: electrocautery and a high-power diode laser. Fifty-seven patients were randomly allocated to two groups (23 submitted to electrocautery and 34 submitted to a high power diode laser). Tongue movements were evaluated based on a clinical assessment and using the Bristol Tongue Assessment Tool (BTAT) before and 15 days after the surgical procedures. The visual analog scale was administered to the mothers on the same occasions for the measurement of pain during breastfeeding. Both groups had an increased BTAT score (favorable outcome) at the post-surgical evaluation, but the anterior third of the tongue was not always free to enable the movements necessary for lingual functions. It is fundamental for surgeons to have skill and in-depth knowledge of the equipment used to avoid accidents and complications in the region of important structures. Both techniques employed in this study were safe and effective, causing little bleeding and few postoperative complications. The group submitted to a high-power diode laser exhibited less post-surgical bleeding compared to the group submitted to electrocautery and no inflammation at the edges of the surgical cut.

Effect of photobiomodulation on fatigue in individuals with relapsing-remitting multiple sclerosis: a pilot study.

Multiple sclerosis is an autoimmune disease of the central nervous system characterized by inflammation and destruction of the myelin sheath. Fatigue is one of the main symptoms of this disease, with a negative impact on quality of life and few treatment options. Photobiomodulation is used for several inflammatory conditions and may be beneficial for the treatment of fatigue in individuals with multiple sclerosis. Conduct a pilot study to analyze the effect of photobiomodulation on fatigue in individuals with relapsing-remitting multiple sclerosis. The participants were recruited from the UNINOVE Integrated Health Clinic and randomly allocated to two groups: group 1, administration of photobiomodulation (808 nm, 36 J for 360 s) under the tongue and group 2, administration of photobiomodulation over the radial artery. Fatigue was measured using the Modified Fatigue Impact Scale (MFIS). No significant differences were found regarding the total MFIS score or subscale scores (p < 0.05, two-way ANOVA). Photobiomodulation with the parameters employed in the present study had no effect on fatigue in individuals with multiple sclerosis. ClinicalTrials.gov Identifier: NCT03360487.

Effects of photobiomodulation in experimental spinal cord injury models: A systematic review.

This systematic review investigated the repercussions of photobiomodulation using low-level laser therapy (LLLT) for the treatment of spinal cord injury (SCI) in experimental models. Studies were identified from relevant databases published between January 2009 and December 2021. Nineteen original articles were selected and 68.4% used light at an infrared wavelength. There was a considerable variation of the power used (from 25 to 200 mW), total application time (8-3000 s) and total energy (0.3-450 J). In 79% of the studies, irradiation was initiated immediately after or within 2 h of the SCI, and treatment time ranged continuously from 5 to 21 days. In conclusion, LLLT can be an auxiliary therapy in the treatment of SCI, playing a neuroprotective role, enabling functional recovery, increasing the concentration of nerve connections around the injury site and reducing pro-inflammatory cytokines. However, there is a need for standardization in the dosimetric parameters.

Empagliflozin Alleviates Left Ventricle Hypertrophy in High-Fat-Fed Mice by Modulating Renin Angiotensin Pathway.

Aims. The cardiobenefits of empagliflozin are multidimensional, and some mechanisms are still unclear. The aim of the present study was to evaluate the effect of treatment with empagliflozin on biometric parameters and gene expression in the local cardiac RAS, oxidative stress, and endoplasmic reticulum pathways in a mouse model. Main Methods. Forty male C57BL/6 mice were fed with control (C) or high-fat (HF) diets for 10 weeks. After that, the groups were redistributed according to the treatment with empagliflozin-CE or HFE. The empagliflozin was administered via food for 5 weeks (10 mg/kg/day). We performed biochemical analyses, blood pressure monitoring, oral glucose tolerance test, left ventricle (LV) stereology, RT-qPCR for genes related to classical and counterregulatory local RAS, oxidative stress, and endoplasmic reticulum stress. Key Findings. In comparison to HF, HFE decreased body mass and improved glucose intolerance and insulin resistance. The cardiac parameters were enhanced after treatment as expressed by decrease in plasma cholesterol, plasma uric acid, and systolic blood pressure. In addition, LV analysis showed that empagliflozin reduces cardiomyocyte area and LV thickness. The local RAS had less activity of the classical pathway and positive effects on the counterregulatory pathway. Empagliflozin treatment also decreased oxidative stress and endoplasmic reticulum stress-related genes. Significance. Our results suggests that empagliflozin modulates the local RAS pathway towards alleviation of oxidative stress and ER stress in the LV, which may be a route to its effects on improved cardiac remodeling.

Photobiomodulation for the Treatment of Primary Headache: Systematic Review of Randomized Clinical Trials.

The purpose of this study was to evaluate the efficacy and safety of photobiomodulation as an adjuvant treatment for primary headache. A systematic review of randomized clinical trials was performed. For such, electronic searches were performed in the MEDLINE, Embase, Cochrane Library, LILACS, PEDro, PsycInfo, Clinicaltrials.gov., and WHO/ICTRP databases, with no restrictions imposed regarding language or year of publication. We included studies that assessed any photobiomodulation therapy as an adjuvant treatment for primary headache compared to sham treatment, no treatment, or another intervention. The methodological assessment was conducted using the Cochrane Risk of Bias tool. The certainty of the evidence was classified using the GRADE approach. Four randomized clinical trials were included. Most of the included studies had an overall high risk of bias. Compared to sham treatment, photobiomodulation had a clinically important effect on pain in individuals with primary headache. Despite the benefits reported for other outcomes, the estimates were imprecise, and the certainty of the evidence was graded as low. These findings are considered insufficient to support the use of photobiomodulation in the treatment of primary headache. Randomized clinical trials, with higher methodological quality, are needed to enhance the reliability of the estimated effects.

Efficacy and safety of electrical stimulation in the treatment of neurogenic bladder dysfunction in myelomeningocele-Systematic review of randomized clinical trials.

AIMS: The purpose of this systematic review was to investigate and synthesize the effects (benefits and harms) of electrical stimulation (EE), alone or in association with other interventions, compared with sham and other interventions, for the treatment of neurogenic bladder dysfunction in myelomeningocele. METHODS: This systematic review was conducted following the methodological recommendations of the Cochrane Handbook for Systematic Reviews of Interventions and registered at PROSPERO (CRD42020200425). A search was performed in the following electronic databases: MEDLINE, Cochrane Central Register of Controlled Trials, EMBASE, LILACS, and PEDro. Randomized clinical trials (RCTs) that assessed any EE in children diagnosed with myelomeningocele and neurogenic bladder and/or urinary incontinence were included and reported. RESULTS: When comparing EE versus sham groups, some estimated effects showed a wide confidence interval, probably due to the small sample size of the included studies. This indicates an imprecision in these findings. Regarding the safety of this intervention and safety of the lower urinary tract, no adverse events resulting from EE were reported. All the included studies have evaluated the efficacy of EE compared with sham, but different EE parameters and electrode positions among studies make it impossible to perform a meta-analysis. CONCLUSIONS: Based on very low certainty evidence, the findings of this systematic review suggested no difference between EE and sham to improve urinary incontinence in children with myelomeningocele. However, the small sample size and the imprecision arising from the wide confidence intervals must be considered. Future RCTs following a rigorous methodology, as recommended by the CONSORT statement, should be conducted to support the use of this intervention in clinical practice.