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.

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.

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.

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.

Complete and Fast Recovery from Idiopathic Facial Paralysis Using Laser-Photobiomodulation.

Idiopathic facial paralysis, also known as Bell's palsy, exerts a negative effect on the quality of life. Although the prognosis is good in the majority of cases, a significant percentage of affected individuals may have sequelae that can negatively affect their lives. The use of therapeutic measures as early as possible can improve the prognosis. This article describes the successful use of laser-photobiomodulation as a single therapy in a patient with Bell's palsy and confirms the possibility of using this therapeutic modality as a good choice, since it is a therapy that is painless, comfortable, and without systemic side effects. The findings demonstrate that the adequate use of laser-photobiomodulation can be an effective therapeutic option for patients with Bell's palsy, regardless of the age, shortening the recovery time obtained with conventional therapies and avoiding sequelae. Further studies are needed for the establishment of adequate protocols.

Extracellular Vesicles isolated from Mesenchymal Stromal Cells Modulate CD4+ T Lymphocytes Toward a Regulatory Profile.

Mesenchymal stromal cells (MSCs) can generate immunological tolerance due to their regulatory activity in many immune cells. Extracellular vesicles (EVs) release is a pivotal mechanism by which MSCs exert their actions. In this study, we evaluate whether mesenchymal stromal cell extracellular vesicles (MSC-EVs) can modulate T cell response. MSCs were expanded and EVs were obtained by differential ultracentrifugation of the supernatant. The incorporation of MSC-EVs by T cells was detected by confocal microscopy. Expression of surface markers was detected by flow cytometry or CytoFLEX and cytokines were detected by RT-PCR, FACS and confocal microscopy and a miRNA PCR array was performed. We demonstrated that MSC-EVs were incorporated by lymphocytes in vitro and decreased T cell proliferation and Th1 differentiation. Interestingly, in Th1 polarization, MSC-EVs increased Foxp3 expression and generated a subpopulation of IFN-γ+/Foxp3+T cells with suppressive capacity. A differential expression profile of miRNAs in MSC-EVs-treated Th1 cells was seen, and also a modulation of one of their target genes, TGFbR2. MSC-EVs altered the metabolism of Th1-differentiated T cells, suggesting the involvement of the TGF-ß pathway in this metabolic modulation. The addition of MSC-EVs in vivo, in an OVA immunization model, generated cells Foxp3+. Thus, our findings suggest that MSC-EVs are able to specifically modulate activated T cells at an alternative regulatory profile by miRNAs and metabolism shifting.

A universal mathematical model applied to the congenital ventral penile curvature.

INTRODUCTION: The macroscopic dynamic of fetal penis development presents a pattern resembling the unfolding of a spiral, so congenital ventral penile curvature could indicate that this natural sequence has been interrupted. Our aim in this article is to offer a mathematical model of congenital ventral curvature of the penis. MATERIALS AND METHODS: Five individuals who presented with congenital ventral penile curvature and three who presented with acquired penile ventral curvature due to Peyronie's disease were evaluated. The penises were photographed during an induced erection test and the penile curvature patterns were compared with an equiangular spiral. When an association was found, a potential relationship to the golden spiral-a type of equiangular spiral-was also assessed. The mathematical spiral relationships were analyzed using Wolfram CDF Player® (Logarithmic Spiral) and PhiMatrix® software. The Wolfram software generated logarithmic spirals equivalent to the penile curvature with appropriate mathematical values. The PhiMatrix software, which builds any golden spirals from golden rectangles, was used to check whether the spiral was golden as well as equiangular. RESULTS: An equiangular spiral that was also golden was found in all cases of congenital ventral penile curvature. In contrast, none of the acquired penile ventral curvature cases showed a specific pattern. CONCLUSION: Congenital ventral penile curvature has the mathematical pattern of a golden spiral. Our results offer a mathematical algorithm for potential use in surgical reconstruction procedures, regenerative medicine, tissue engineering, robotics, and body-machine interfaces.

Evaluation of the use of photobiomodulation following the placement of elastomeric separators: Protocol for a randomized controlled clinical trial.

BACKGROUND: Pain stemming from the placement of elastomeric separators and the exchanging of wires and accessories is the greatest reason for abandoning orthodontic treatment. Indeed, discomfort related to treatment exerts a negative impact on quality of life due to the difficulty chewing and biting. This paper proposes a study to evaluate the analgesic effects of photomiobodulation (PBM) on individuals undergoing orthodontic treatment. METHODS: The sample will be composed of 72 individuals who receiving elastomeric separators on the mesial and distal faces of the maxillary first molars. The patients will be randomly allocated to 2 groups: an experimental group irradiated with low-level laser and a sham group submitted to simulated laser irradiation. Upon the placement of the separators, the experimental group will receive a single application of PBM on the mesial and distal cervical portion and apical third of the molars. Perceived pain will be analyzed after one hour using the visual analog scale in both groups. Samples will be taken of the gingival crevice with absorbent paper for 30 seconds for the analysis of cytokines using ELISA and the results of the 2 groups will be compared. The patients will sign a statement of informed consent. Statistical analysis will be performed with the Student's t test and analysis of variance (ANOVA). DISCUSSION: The expectation is that the patients in the irradiated group will have a lower perception of pain and lower quantity of cytokines compared to those in the sham group. The purpose of the study is to establish an effective method for PBM with the use of low-level infrared laser (Ga-Al-As with a wavelength of 808 nm and output power of 100 mW) for reductions in pain and inflammatory cytokines related to orthodontic treatment. TRIAL REGISTRATION: This protocol was registered in ClinicalTrial.gov, under number NCT03939988. It was first posted and last updated in May 6, 2019.

Empaglifozin mitigates NAFLD in high-fat-fed mice by alleviating insulin resistance, lipogenesis and ER stress.

AIM: To evaluate the pleiotropic effects of empagliflozin in the liver through lipogenesis, beta-oxidation, and endoplasmic reticulum stress pathways. METHODS: Male C57Bl/6 mice, 3 months of age, received a control diet (C, 10% lipids, n = 20) or high-fat diet (HF, 50% lipids, n = 20) for 10 weeks, after that, the groups were subdivided to receive empagliflozin, during 5 weeks at a dose of 10 mg/kg/day added to the diets, totalizing four groups: C, C-EMPA, HF, and HF-EMPA. We performed biochemical analyzes, oral glucose tolerance test, homeostasis model assessment of insulin resistance (HOMA-IR), indirect calorimetry, liver stereology, western blotting, RT-qPCR for genes related to beta-oxidation, lipogenesis, and endoplasmic reticulum stress. RESULTS: After the treatment with empagliflozin, there was a 4% increase in energy expenditure, a 5% reduction in body mass, improvement in glucose tolerance and insulin sensitivity and insulin resistance. The expression of Ppar alpha was greater in the HF-EMPA group with a concomitant reduction in the expression of the lipogenic genes Fas, Srebp1c and Ppar gamma, according to protein expression. In addition, HF-EMPA showed a reduction in the genes related to endoplasmic reticulum stress Chop, Atf4, and Gadd45. CONCLUSION: Empagliflozin mitigates the development of NAFLD, confirmed through reduced expression of the genes involved in hepatic lipogenesis and genes involved in endoplasmic reticulum stress. Thus, empagliflozin may be an important tool to treat the progression of hepatic steatosis.

Effect of irradiation with intravascular laser on the hemodynamic variables of hypertensive patients: Study protocol for prospective blinded randomized clinical trial.

BACKGROUND: High blood pressure (HBP) is a multifactorial clinical condition, with a high morbidity and mortality rate and low rates of control. Due to its high prevalence, it is necessary to search for methods which aim to improve the quality of life of hypertensive patients. Studies have shown that low level laser therapy (LLLT) is capable of inducing a photobiological response within the cells which modifies the micro and macrovascular response; this accompanies evidence showing the systemic effects of intravascular laser irradiation of blood (ILIB). In the hypothesis that the use of LLLT can influence blood pressure levels, and perhaps facilitate adherence to treatment, this study aims to present a clinical research protocol with the goal of determining the effect of photobiomodulation in relation to changes in the hemodynamic parameters of hypertensive and normotensive patients. METHOD: Forty-four participants, frequent attendees of an ambulatory university clinic, will be subdivided into 4 groups, and then submitted to protocol sessions of ILIB. The technique is noninvasive and consists of a laser which is attached to a bracelet which has been specifically developed for the light beam to be transcutaneously carried over the radial artery. Before the procedure, at the end of the photobiomodulation cycles, and 1 month after the end of therapy, blood samples will be collected for the evaluation of C-reactive protein, interleukin 6, and nitric oxide, to be analyzed by immunoturbidimetric, ELISA, and Griess reactions, respectively. ANALYSIS OF RESULTS: Results will be analyzed using descriptive and inferential statistics and will be compiled into tables and/or graphs, with the help of SPSS version 24.0 with the adopted significance level for all tests being α = 0.05. DISCUSSION: The treatment of HBP involves both pharmacological and nonpharmacological therapy. Animal studies with photobiomodulation have previously shown hypotensive effects. Gaps in the literature exist regarding the applicability of this nonpharmacological therapy in humans. This study aims to consider the possibility of offering nonpharmacological therapy to hypertensive patients with the goal of increasing adherence to the treatment as well as minimizing morbidity and mortality caused by hypertension.

Effect of photobiomodulation treatment in the sublingual, radial artery region, and along the spinal column in individuals with multiple sclerosis: Protocol for a randomized, controlled, double-blind, clinical trial.

BACKGROUND: Multiple sclerosis (MS) is an autoimmune disease, for which the forms of treatment are medication and rehabilitation. However, in vitro and in vivo studies have demonstrated that photobiomodulation can be an effective treatment modality for inflammatory diseases, including MS. Photobiomodulation has a broad range of benefits, such as the avoidance of cell and tissue death, the stimulation of healing and injury repair, reductions in pain, edema and inflammation, cell proliferation, and even apoptosis. The outcomes of photobiomodulation include the regeneration of cells, the stimulation of the growth of Schwann cells, a reduction in spasticity, functional improvements, a reduction in nitric oxide levels, and the upregulation of the cytokine IL10, demonstrating that this therapeutic modality can offer neuroprotection. METHODS: A randomized, controlled, double-blind, clinical trial is proposed. The patients will be divided into 6 groups. Groups 1 and 2 will receive sham and active photobiomodulation in the sublingual region, respectively. Groups 3 and 4 will receive sham and active photobiomodulation along the spinal cord, respectively. Group 5 will receive placebo treatment with photobiomodulation on the skin in the region of the radial artery with a specific bracelet. Group 6 will be treated with photobiomodulation on the skin in the region of the radial artery. DISCUSSION: Treatment for MS is directed at the immune response and slowing the progression of the disease. This is one of the first clinical trials involving photobiomodulation in the sublingual region and along the spinal cord, which could help establish a promising new form of nonpharmacological treatment for autoimmune diseases. This is one of the first clinical trials with sublingual photobiomodulation and along the spinal cord that could help establish a new form of promising treatment of the disease associated with pharmacological treatment.

Limited utility of Kinesio Taping® in the physiotherapy treatment for patients with chronic obstructive pulmonary disease exacerbation.

BACKGROUND: Kinesio Taping® has been used as a physiotherapy treatment in musculoskeletal disorders. However, few studies have evaluated its effectiveness in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVES: To analyze the effects of Kinesio Taping® associated with conventional physiotherapy, on the maximal inspiratory and expiratory pressures (MIP and MEP), forced expiratory volume in 1 second (FEV1), peak expiratory flow (PEF), and pulse oxygen saturation (SpO2) of patients hospitalized for COPD exacerbation. METHODS: Prospective, randomized, single-blinded study. Sixty-two participants who were randomized into two groups: 1) control (medication and standard physiotherapy treatment); and 2) Kinesio Taping® (standard treatment plus application of Kinesio Taping® on the respiratory muscles). The outcomes were assessed 24 hours after the treatment. RESULTS: After the intervention, the Kinesio Taping® group showed a statistically significant increase in all outcomes assessed. However, when the mean differences between groups were analyzed, there were no statistically significant differences in MIP, MEP, FEV1, and PEF. Differences were found only in SpO2 that was improved in the Kinesio Taping® group. CONCLUSIONS: The application of Kinesio Taping® associated with physiotherapy improved SpO2 of non-hypoxemic patients with COPD exacerbation. Further studies should be conducted to evaluate the method in the long run and in another outcome.

Mutations in INPP5K, Encoding a Phosphoinositide 5-Phosphatase, Cause Congenital Muscular Dystrophy with Cataracts and Mild Cognitive Impairment.

Phosphoinositides are small phospholipids that control diverse cellular downstream signaling events. Their spatial and temporal availability is tightly regulated by a set of specific lipid kinases and phosphatases. Congenital muscular dystrophies are hereditary disorders characterized by hypotonia and weakness from birth with variable eye and central nervous system involvement. In individuals exhibiting congenital muscular dystrophy, early-onset cataracts, and mild intellectual disability but normal cranial magnetic resonance imaging, we identified bi-allelic mutations in INPP5K, encoding inositol polyphosphate-5-phosphatase K. Mutations impaired phosphatase activity toward the phosphoinositide phosphatidylinositol (4,5)-bisphosphate or altered the subcellular localization of INPP5K. Downregulation of INPP5K orthologs in zebrafish embryos disrupted muscle fiber morphology and resulted in abnormal eye development. These data link congenital muscular dystrophies to defective phosphoinositide 5-phosphatase activity that is becoming increasingly recognized for its role in mediating pivotal cellular mechanisms contributing to disease.

IGF2/ApaI polymorphism associated with birth weight in children of the region of Petrolina-PE, Brazil.

Insulin-like growth factor 2 (IGF2) gene has an important role in fetal growth. It was investigated association of the IGF2/ApaI polymorphism with low birth weight and normal birth weight (as control) in children attended in Hospital Dom Malan Petrolina, PE-Brazil. The genotype frequencies did not differ statistically between low birth weight (AA = 16.22%, AG = 43.24%, GG = 40.54%) and control (AA = 20% AG = 35%, GG= 45% groups) and the allele frequencies were not significantly different (p > 0.05).The observed genotype frequencies in both groups did not deviate significantly from Hardy-Weinberg equilibrium. Then, no significant correlation was found for this polymorphism in the population studied.