Biosensor capability of the endometrium is mediated in part, by altered miRNA cargo from conceptus-derived extracellular vesicles.

We tested the hypothesis that the biosensor capability of the endometrium is mediated in part, by the effect of different cargo contained in the extracellular vesicles secreted by the conceptus during the peri-implantation period of pregnancy. We transferred Bos taurus taurus embryos of different origin, in vivo (high developmental potential (IV)), in vitro (intermediate developmental potential (IVF)), or cloned (low developmental potential (NT)), into Bos taurus indicus recipients. Extracellular vesicles (EVs) recovered from Day 16 conceptus-conditioned medium were characterized and their microRNA (miRNA) cargo sequenced alongside RNA sequencing of their respective endometria. There were substantial differences in the endometrial response to in vivo versus in vitro and in vivo versus cloned conceptuses (1153 and 334DEGs respectively) with limited differences between in vitro Vs cloned conceptuses (36 DEGs). The miRNA cargo contained in conceptus-derived EVs was similar between all three groups (426 miRNA in common). Only 8 miRNAs were different between in vivo and cloned conceptuses, while only 6 miRNAs were different between in vivo and in vitro-derived conceptuses. Treatment of endometrial epithelial cells with mimic or inhibitors for miR-128 and miR-1298 changed the proteomic content of target cells (96 and 85, respectively) of which mRNAs are altered in the endometrium in vivo (PLXDC2, COPG1, HSPA12A, MCM5, TBL1XR1, and TTF). In conclusion, we have determined that the biosensor capability of the endometrium is mediated in part, by its response to different EVs miRNA cargo produced by the conceptus during the peri-implantation period of pregnancy.

Lychnophora pinaster in endangered campos rupestres: phenolic compounds and population ecogeography.

Lychnophora pinaster, known as arnica-mineira, is endemic to campos rupestres, at risk of extinction. The present study aimed to characterize the ecogeography and phenolic constituents of 11 L. pinaster populations collected in the mesoregions North, Jequitinhonha, Metropolitan of Belo Horizonte and Campos das Vertentes in the state of Minas Gerais, Brazil. Phenolic constituents were identified and quantified by Ultra-high performance liquid chromatography- mass spectrometry. Lychnophora pinaster occurs in sites at high altitude (700 and 1498 m), annual rainfall of up to 1455 m, soils with low fertility and predominantly loamy texture. Therefore, it can be considered tolerant to acidic soils, with low availability of nutrient. The most abundant substances in all populations were vitexin (18 - 1345 ng/g) and chlorogenic acid (60 - 767 ng/g). The 11 populations formed four groups in relation to the phenolic constituents, with group 1 consisting of the populations of the North Mesoregion (GM, OD) and Jetiquinhonha (DIMa), group 2, the Metropolitan of Belo Horizonte (SRM, NLSC, SM, RPS, CTRA), group 3, the North Mesoregion (ODMa and DI), and group 4, the Campos das Vertentes (CC). Among the populations, only those from the Metropolitan of Belo Horizonte showed correlation of soil properties with phenolic constituents.

Effect of extreme mechanical densification on the electrical properties of carbon nanotube micro-yarns.

We have explored the effect of high pressure post-treatment in optimizing the properties of carbon nanotube yarns and found that the application of dry hydrostatic pressure reduces porosity and enhances electrical properties. The CNT yarns were prepared by the dry-spinning method directly from CNT arrays made by the hot filament chemical vapour deposition (HF-CVD) process. Mechanical hydrostatic pressure up to 360 MPa induces a decrease in yarn resistivity between 3% and 35%, associated with the sample's permanent densification, with CNT yarn diameter reduction of 10%-25%. However, when increasing the pressure in the 1-3 GPa domain in non-hydrostatic conditions, the recovered samples show lower electrical conductivity. This might be due to concomitant macroscopic effects such as increased twists and damage to the yarn shown by SEM imaging (caused by strong shear stresses and friction) or by the collapse of the CNTs indicated byin situhigh pressure Raman spectroscopy data.

Refining details of the structural and electronic properties of the CuB site in pMMO enzyme through sequential molecular dynamics/CPKS-EPR calculations.

This work investigated the structural and electronic properties of the copper mononuclear site of the PmoB part of the pMMO enzyme at the molecular level. We propose that the CuB catalytic site in the soluble portion of pMMO at room temperature and under physiological conditions is a mononuclear copper complex in a distorted octahedral arrangement with the residues His33, His137, and His139 on the equatorial base and two water molecules on the axial axis. Our view was based on the molecular dynamics results and DFT calculations of the electronic paramagnetic resonance parameters and comparisons with experimental EPR data. This new proposed model for the CuB site brings additional support concerning the recent experimental evidence, which pointed out that a saturated coordination sphere of the copper ion in the CuB center is an essential factor that makes it less efficient than the CuC site in the methane oxidation. Therefore, according to the CuB site model proposed here, an additional step involving a displacement of at least one water molecule of the copper coordination sphere by the O2 molecule prior to its activation must be necessary. This scenario is less likely to occur in the CuC center once this one is buried in the alpha-helices, which are part of the pMMO structure bound to the membrane wall, and consequently located in a less solvent-exposed region. In addition, we also present a simple and efficient sequential S-MD/CPKS protocol to compute EPR parameters that can, in principle, be expanded for the study of other copper-containing proteins.

What Do the Transcriptome and Proteome of Menstrual Blood-Derived Mesenchymal Stem Cells Tell Us about Endometriosis?

Given the importance of menstrual blood in the pathogenesis of endometriosis and the multifunctional roles of menstrual mesenchymal stem cells (MenSCs) in regenerative medicine, this issue has gained prominence in the scientific community. Moreover, recent reviews highlight how robust the integrated assessment of omics data are for endometriosis. To our knowledge, no study has applied the multi-omics approaches to endometriosis MenSCs. This is a case-control study at a university-affiliated hospital. MenSCs transcriptome and proteome data were obtained by RNA-seq and UHPLC-MS/MS detection. Among the differentially expressed proteins and genes, we emphasize ATF3, ID1, ID3, FOSB, SNAI1, NR4A1, EGR1, LAMC3, and ZFP36 genes and MT2A, TYMP, COL1A1, COL6A2, and NID2 proteins that were already reported in the endometriosis. Our functional enrichment analysis reveals integrated modulating signaling pathways such as epithelial-mesenchymal transition (↑) and PI3K signaling via AKT to mTORC1 (↓ in proteome), mTORC1 signaling, TGF beta signaling, TNFA signaling via NFkB, IL6 STAT3 signaling, and response to hypoxia via HIF1A targets (↑ in transcriptome). Our findings highlight primary changes in the endometriosis MenSCs, suggesting that the chronic inflammatory endometrial microenvironment can modulate these cells, providing opportunities for endometriosis etiopathogenesis. Moreover, they identify challenges for future research leveraging knowledge for regenerative and precision medicine in endometriosis.

Improvement in Solubility-Permeability Interplay of Psoralens from Brosimum gaudichaudii Plant Extract upon Complexation with Hydroxypropyl-ß-cyclodextrin.

Psoralen (PSO) and 5-methoxypsoralen (5-MOP) are widely used drugs in oral photochemotherapy against vitiligo and major bioactive components of root bark extract of Brosimum gaudichaudii Trécul (EBGT), previously standardized by LC-MS. However, the exceptionally low water solubility of these psoralens can cause incomplete and variable bioavailability limiting their applications and patient adherence to treatment. Therefore, the purpose of this work was to investigate the effects of 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD) inclusion complex on the solubility and jejunal permeability of PSO and 5-MOP from EBGT. Characterization of inclusion complexes were evaluated by current methods in nuclear magnetic resonance studies on aqueous solution, Fourier transform infrared spectroscopy, thermal analysis, and scanning electron microscopy in solid state. Ex vivo rat jejunal permeability was also investigated and compared for both pure psoralens and plant extract formulation over a wide HP-ß-CD concentration range (2.5 to 70 mM). Phase solubility studies of the PSO- and 5-MOP-HP-ß-CD inclusion complex showed 1:1 inclusion complex formation with small stability constants (Kc < 500 M−1). PSO and 5-MOP permeability rate decreased after adding HP-ß-CD by 6- and 4-fold for pure standards and EBGT markers, respectively. Nevertheless, the complexation with HP-ß-CD significantly improved solubility of PSO (until 10-fold) and 5-MOP (until 31-fold). As a result, the permeability drop could be overcome by solubility augmentation, implying that the HP-ß-CD inclusion complexes with PSO, 5-MOP, or EBGT can be a valuable tool for designing and developing novel oral drug product formulation containing these psoralens for the treatment of vitiligo.

Small extracellular vesicles derived from in vivo- or in vitro-produced bovine blastocysts have different miRNAs profiles-Implications for embryo-maternal recognition.

In vivo- and in vitro-produced bovine embryos have different metabolic profiles and differences in gene transcription patterns. These embryos also have a distinct ability to establish and sustain early pregnancies. Small extracellular vesicles (sEVs) are secreted by embryos and carry bioactive molecules, such as miRNAs. We hypothesize that in vivo or in vitro-produced bovine hatched blastocysts on Day 9 and the sEVs secreted by them have different miRNA profiles. To address this hypothesis, embryos of both groups were placed in in vitro culture on Day 7. After 48 h, hatched embryos and hatched embryo-conditioned media (eCM) of both groups were collected. A total of 210 miRNAs were detected in embryos of both groups, of these 6 miRNAs were downregulated, while 7 miRNAs were upregulated in vitro group when compared to in vivo group. sEVs were isolated from eCM to determine miRNA profile. A total of 106 miRNAs were detected in both groups, including 14 miRNAs upregulated in sEVs from in vivo-eCM, and 2 miRNAs upregulated in sEVs from in vitro-eCM. These miRNAs express in embryos and sEVs secreted by them regulate early embryonic developmental and endometrial pathways, which can modify embryo-maternal communication during early pregnancy and consequently affect pregnancy establishment.

Physiological and Perceptual Responses to Aerobic Exercise With and Without Blood Flow Restriction.

ABSTRACT: Silva, JCG, Domingos-Gomes, JR, Freitas, EDS, Neto, GR, Aniceto, RR, Bemben, MG, Lima-dos-Santos, A, and Cirilo-Sousa, MS. Physiological and perceptual responses to aerobic exercise with and without blood flow restriction. J Strength Cond Res 35(9): 2479-2485, 2021-Although previous studies have demonstrated the potential benefits of aerobic exercise (AE) with blood flow restriction (BFR), these findings have been limited by the approaches used to determine the occlusive pressure. In addition, the physiological and perceptual responses of AE with BFR compared to high-intensity interval exercise (HIIE) remain unclear. Thus, we investigated the physiological and perceptual responses to AE with and without BFR, and HIIE. Twenty-two men were randomly assigned to 4 experimental conditions: AE (40% of maximal oxygen consumption [V˙o2peak]), AE with 50% of BFR (AE-BFR: 40% VV˙o2peak), HIIE (80% V˙o2peak), and a no exercise control condition (CON: 50% of BFR). Each exercise bout lasted 18 minutes, during which oxygen consumption (V˙o2), heart rate (HR), and ratings of perceived exertion (RPE) were measured at rest and at every 3 minutes during exercise. Ratings of discomfort before and after each trial. The HIIE condition induced the greatest increases in V˙o2 and HR (p < 0.05), whereas AE-BFR was significantly (p < 0.05) greater than AE and CON. HIIE and AE-BFR also elicited the greatest (p < 0.05), but similar (p > 0.05), increases in RPE during exercise, although AE-BFR was significantly greater than HIIE immediately after exercise (p < 0.05). AE-BFR and HIIE also induced similar levels of discomfort after exercise (p > 0.05). In conclusion, HIIE induced the greatest increases in V˙o2 and HR, although the perceptual responses were essentially the same compared with AE-BFR. However, albeit inferior to HIIE, V˙o2 was greater during AE-BFR compared with AE, indicating that this training method may be used to replace HIIE and still significantly elevate V˙o2.

Evaluation of atmospheric particulate matter from an industrial area in Southeast Brazil.

A large number of pollutants, such as trace elements, can be found on the surface of atmospheric particulate matter. Since some trace elements can be hazardous to humans, monitoring the atmospheric emissions is relevant to generate comparative data over the years and to predict the health risks of the exposed population. Thus, the aim of this study was to monitor the concentrations of trace elements in atmospheric particulate matter samples from an industrial area in the city of Juiz de Fora, Minas Gerais, in Southeast Brazil. After the sampling campaign, the samples (n = 22) were prepared with microwave-assisted extraction and analyzed by atomic absorption spectrometry. Then, the analyte results were evaluated through statistical approaches. The enrichment factor calculation, Pearson correlation, principal component analysis, and hierarchical cluster analysis were used to identify the main source of each analyte. The samples presented high levels of Al and Fe, which were mainly associated with natural sources, such as resuspension of soil dust. Cr and Mn mostly can come from natural origin. The anthropogenic influence showed increasing trends for As and Cu, indicating that these elements can be from sources other than natural ones, such as industrial processes and vehicle emissions. Furthermore, extremely high enrichment was observed for Cd, Pb, and Zn, indicating strong anthropogenic impact, which may be related to industrial activity in this area. Thus, the industrial emissions were probably the main source of these analytes in the investigated samples.

Evaluation of Plasmodium vivax malaria recurrence in Brazil.

BACKGROUND: Control of vivax malaria in endemic areas requires management of recurrence. The Brazilian National Malaria Surveillance System (SIVEP-Malária) records every case of malaria in Brazil, but is not designed to differentiate between primary and recurrent infections. The aim of this study was to explore whether the information provided by SIVEP-Malária could be used to identify Plasmodium vivax recurrences, its risk factors and evaluate the effectiveness of short course primaquine (7-9 days: total dose 3-4.2 mg/kg) in preventing relapses. METHODS: In this observational retrospective cohort study, data matching of SIVEP-Malária records was undertaken using bloom filters to identify potential recurrences defined as microscopically-confirmed P. vivax episodes from the same individual occurring within a year. Generalized Estimation Equation (GEE) models were used to determine predictors of recurrence. Extended Cox-based conditional Prentice-Williams-Peterson models (PWP) models were used to evaluate time to recurrence. RESULTS: Between June 1, 2014 and May 31, 2015, 26,295 episodes fulfilled the criteria of potential recurrence among 154,970 reported malaria episodes. Age ≤ 3 years, being male, literate, not-indigenous and having domestic working activities were identified as risk factors for recurrence. There was no difference in time to recurrence or recurrence frequency between patients treated with 14-day or 7-9 day primaquine regimens (HR = 1.02, 0.96-1.09) and RR = 0.97 (0.90-1.04), respectively. The use of chloroquine alone was associated with a 1.43 (1.29-1.58, p < 0.0001) increased risk of P. vivax recurrence compared to patients who used chloroquine combined with short-course primaquine, the Brazilian standard of care. This was RR = 2.06 (1.48-2.86, p < 0.0001), RR = 1.90 (1.60-2.25, p = 0.0001) and RR = 1.14 (1.00-1.29, p = 0.05) for recurrences occurring between 3-28, 29-60 and > 60 days, respectively. PWP models showed that the time to recurrence was longer in recipients of both primaquine and artemisinin-based combination therapy (ACT) compared to patients treated with chloroquine alone or with concomitant primaquine, HR = 2.2 (1.62-2.99, p < 0.0001), HR = 1.27 (0.97-1.66, p = 0.08), respectively. CONCLUSION: Short course primaquine was as effective as 14-day regimens and associated with a halving of the risk and delay in time to recurrence of P. vivax infections in comparison to chloroquine alone. The study demonstrates the feasibility of using record linkage on routine surveillance data to identify potential P. vivax recurrences, associated risk factors and impact of treatment.

Exudate - phenolphthalein pH test for evaluation of validity in seeds of Libidibia ferrea.

Seed companies are looking for promising, quick and effective alternatives to determine the physiological quality of seeds. The objective of the current work was to study the efficiency of the exudate - phenolphthalein pH test to evaluate the seeds of two lots of Libidibia ferrea (Mart. ex Tul.) L. P. Queiroz var. ferrea. The statistical design for the the exudate - phenolphthalein pH test was completely randomized with four replicates of 50 seeds in a factorial design (2 x 5), two seed lots and five soaking periods (30, 60, 90, 120, and 150 minutes), respectively, using two constant temperatures (25 and 30°C). The percentage of viability and germination of the seeds did not differ in the temperatures of 25 and 30°C and in the soaking periods by the exudate - phenolphthalein pH test. Thus, it is recommended that the test be conducted for at least 30 minutes in distilled and deionized water at the constant temperature of 25 or 30°C to evaluate the vigor of the Libidibia ferrea.

Is cytochrome P450 3A4 regulated by menstrual cycle hormones in control endometrium and endometriosis?

The estrogen-metabolizing activities of cytochrome P450 (CYP) enzymes have been implicated in endometriosis. However, their regulation in various sources of endometrial tissue under different hormonal conditions has not been clarified. Our objective was to study the hormone regulation of a specific CYP enzyme, namely CYP3A4, in control (n = 15) and endometriosis patients (n = 42). To this end, we evaluated mRNA expression (using real-time PCR) of CYP3A4 in tissue samples classified according to the phase of menstrual cycle at which they were obtained as confirmed by the related circulating hormone levels. Protein expression was also evaluated by Western Blot. In order to further investigate the hormonal regulation of CYP3A4, stromal cells from ovarian endometriotic lesions were cultured with the prevailing hormones of the distinct phases of the menstrual cycle. We observed that all control and endometriosis tissues express CYP3A4. Nevertheless, changes in CYP3A4 gene expression related to cycle phase were only seen in the control eutopic endometrium and not in samples from endometriosis patients, with an increase in the luteal phase. Stromal cells isolated from ovarian endometriotic lesions expressed CYP3A4 and their exposure to luteal phase-mimicking hormones (estradiol + progesterone) reduced CYP3A4 mRNA in parallel with a diminished expression of the corresponding receptors, estrogen receptor alpha and progesterone receptor. Our findings suggest that steroid hormones are able to regulate CYP3A4 mRNA expression, although the circulating levels of these hormones can only regulate control endometrium and not endometriosis tissues, probably because of dysregulated local steroid concentration in these latter samples.

Single-Amino Acid Modifications Reveal Additional Controls on the Proton Pathway of [FeFe]-Hydrogenase.

The proton pathway of [FeFe]-hydrogenase is essential for enzymatic H2 production and oxidation and is composed of four residues and a water molecule. A computational analysis of this pathway in the [FeFe]-hydrogenase from Clostridium pasteurianum revealed that the solvent-exposed residue of the pathway (Glu282) forms hydrogen bonds to two residues outside of the pathway (Arg286 and Ser320), implying that these residues could function in regulating proton transfer. In this study, we show that substituting Arg286 with leucine eliminates hydrogen bonding with Glu282 and results in an ∼3-fold enhancement of H2 production activity when methyl viologen is used as an electron donor, suggesting that Arg286 may help control the rate of proton delivery. In contrast, substitution of Ser320 with alanine reduces the rate ∼5-fold, implying that it either acts as a member of the pathway or influences Glu282 to permit proton transfer. Interestingly, quantum mechanics/molecular mechanics and molecular dynamics calculations indicate that Ser320 does not play a structural role or indirectly influence the barrier for proton movement at the entrance of the channel. Rather, it may act as an additional proton acceptor for the pathway or serve in a regulatory role. While further studies are needed to elucidate the role of Ser320, collectively these data provide insights into the complex proton transport process.

Impact of the Molecular Environment on Thiol-Ene Coupling For Biofunctionalization and Conjugation.

Thiol-ene radical coupling is increasingly used for the biofunctionalization of biomaterials and the formation of 3D hydrogels enabling cell encapsulation. Indeed, thiol-ene chemistry presents interesting features that are particularly attractive for platforms requiring specific reactions of peptides or proteins, in particular, in situ, during cell culture or encapsulation. Despite such interest, little is known about the factors impacting thiol-ene chemistry in situ, under biologically relevant conditions. Here we explore some of the molecular parameters controlling photoinitiated thiol-ene couplings with a series of alkenes and thiols, including peptides, in buffered conditions. (1)H NMR and HPLC were used to quantify the efficiency of couplings and the impact of the pH of the buffer, as well as the molecular structure and local microenvironment close to alkenes and thiols to be coupled. Some of these observations are supported by molecular dynamics and quantum mechanics calculations. An important finding of our work is that the pKa of thiols (and its variation upon changes in molecular structure) have a striking impact on coupling efficiencies. Similarly, positively charged and aromatic amino acids are found to have some impact on thiol-ene couplings. Hence, our study demonstrates that molecular design should be carefully selected in order to achieve high biofunctionalization levels in biomaterials with peptides or promote the efficient formation of peptide-based hydrogels.

Increased expression of CYP1A1 and CYP1B1 in ovarian/peritoneal endometriotic lesions.

Endometriosis is an estrogen-dependent disease affecting up to 10% of all premenopausal women. There is evidence that different endometriosis sites show distinct local estrogen concentration, which, in turn, might be due to a unique local estrogen metabolism. We aimed to investigate whether there was a site-specific regulation of selected enzymes responsible for the oxidative metabolism of estrogens in biopsy samples and endometrial and endometriotic stromal cells. Cytochrome P450 (CYP) 1A1 and CYP1B1 mRNA and protein expressions in deep-infiltrating (rectal, retossigmoidal, and uterossacral) lesions, superficial (ovarian and peritoneal) lesions, and eutopic and healthy (control) endometrium were evaluated by real-time PCR and western blot. Using a cross-sectional study design with 58 premenopausal women who were not under hormonal treatment, we were able to identify an overall increased CYP1A1 and CYP1B1 mRNA expression in superficial lesions compared with the healthy endometrium. CYP1A1 mRNA expression in superficial lesions was also greater than in the eutopic endometrium. Interestingly, we found a similar pattern of CYP1A1 and CYP1B1 expression in in vitro stromal cells isolated from ovarian lesions (n=3) when compared with stromal cells isolated from either rectum lesions or eutopic endometrium. In contradiction, there was an increased half-life of estradiol (measured by HPLC-MS-MS) in ovarian endometriotic stromal cells compared with paired eutopic stromal endometrial cells. Our results indicate that there is a site-dependent regulation of CYP1A1 and CYP1B1 in ovarian/peritoneal lesions and ovarian endometriotic stromal cells, whereas a slower metabolism is taking place in these cells.

Phosphorane lifetime and stereo-electronic effects along the alkaline hydrolysis of phosphate esters.

Hybrid quantum mechanical/effective fragment potential (QM/EFP) calculations, in conjunction with the quantum theory of atoms in molecules (QTAIM) and energy decomposition analysis (EDA), were employed to investigate the reaction mechanism and stereo-electronic effects along the alkaline hydrolysis of the monoethyl phosphate dianion (MEP) and the diethylphosphate monoanion (DEP). Reactions proceed through a synchronous bimolecular ANDN mechanism for MEP and a stepwise (AN + DN) mechanism for DEP, with the formation of a phosphorane intermediate, having an overall reaction free energy and barrier of 11.5 and 43.0 kcal mol(-1), respectively. In addition, ab initio molecular dynamics simulations were performed to investigate the stability of the phosphorane pentacoordinate intermediate observed in the reaction of the phosphate diester. The phosphorane intermediate has a lifetime of ∼1 ps after which it decomposes into the corresponding alcohol and phosphate monoester dianion. Electrostatics governs the interaction between the nucleophile and the phosphate ester. However, some degree of covalence in the interaction starts to appear at distances shorter than 2.45 Šfor MEP and 2.63 Šfor DEP. For the monoester, the electrostatic repulsive terms are the dominant contributions for the formation of the transition state. On the other hand, for the phosphate diester, the formation of the P-OH bond is dominated by associative terms of electrostatic nature.

Mass density and water content of saturated never-dried calcium silicate hydrates.

Calcium silicate hydrates (C-S-H) are the most abundant hydration products in ordinary Portland cement paste. Yet, despite the critical role they play in determining mechanical and transport properties, there is still a debate about their density and exact composition. Here, the site-specific mass density and composition of C-S-H in hydrated cement paste are determined with nanoscale resolution in a nondestructive approach. We used ptychographic X-ray computed tomography in order to determine spatially resolved mass density and water content of the C-S-H within the microstructure of the cement paste. Our findings indicate that the C-S-H at the border of hydrated alite particles possibly have a higher density than the apparent inner-product C-S-H, which is contrary to the common expectations from previous works on hydrated cement paste.

Anaesthetic injection versus ischemic compression for the pain relief of abdominal wall trigger points in women with chronic pelvic pain.

BACKGROUND: Chronic pelvic pain is a common condition among women, and 10 to 30 % of causes originate from the abdominal wall, and are associated with trigger points. Although little is known about their pathophysiology, variable methods have been practiced clinically. The purpose of this study was to evaluate the efficacy of local anaesthetic injections versus ischemic compression via physical therapy for pain relief of abdominal wall trigger points in women with chronic pelvic pain. METHODS: We conducted a parallel group randomized trial including 30 women with chronic pelvic pain with abdominal wall trigger points. Subjects were randomly assigned to one of two intervention groups. One group received an injection of 2 mL 0.5 % lidocaine without a vasoconstrictor into a trigger point. In the other group, ischemic compression via physical therapy was administered at the trigger points three times, with each session lasting for 60 s, and a rest period of 30 s between applications. Both treatments were administered during one weekly session for four weeks. Our primary outcomes were satisfactory clinical response rates and percentages of pain relief. Our secondary outcomes are pain threshold and tolerance at the trigger points. All subjects were evaluated at baseline and 1, 4, and 12 weeks after the interventions. The study was conducted at a tertiary hospital that was associated with a university providing assistance predominantly to working class women who were treated by the public health system. RESULTS: Clinical response rates and pain relief were significantly better at 1, 4, and 12 weeks for those receiving local anaesthetic injections than ischemic compression via physical therapy. The pain relief of women treated with local anaesthetic injections progressively improved at 1, 4, and 12 weeks after intervention. In contrast, women treated with ischemic compression did not show considerable changes in pain relief after intervention. In the local anaesthetic injection group, pain threshold and tolerance improved with time in the absence of significant differences between groups. CONCLUSION: Lidocaine injection seems to be better for reducing the severity of chronic pelvic pain secondary to abdominal wall trigger points compared to ischemic compression via physical therapy. TRIAL REGISTRATION: ClinicalTrials.gov NCT00628355. Date of registration: February 25, 2008.

Endometriosis and physical exercises: a systematic review.

Regular physical exercise seems to have protective effects against diseases that involve inflammatory processes since it induces an increase in the systemic levels of cytokines with anti-inflammatory and antioxidant properties and also acts by reducing estrogen levels. Evidence has suggested that the symptoms associated with endometriosis result from a local inflammatory peritoneal reaction caused by ectopic endometrial implants. Thus, the objective of the present review was to assess the relationship between physical exercise and the prevalence and/or improvement of the symptoms associated with endometriosis. To this end, data available in PubMed (1985-2012) were surveyed using the terms "endometriosis and physical exercises", "endometriosis and life style and physical exercises" in the English language literature. Only 6 of the 935 articles detected were included in the study. These studies tried establish a possible relationship between the practice of physical exercise and the prevalence of endometriosis. The data available are inconclusive regarding the benefits of physical exercise as a risk factor for the disease and no data exist about the potential impact of exercise on the course of the endometriosis. In addition, randomized studies are necessary.

FERM domain interaction with myosin negatively regulates FAK in cardiomyocyte hypertrophy.

Focal adhesion kinase (FAK) regulates cellular processes that affect several aspects of development and disease. The FAK N-terminal FERM (4.1 protein-ezrin-radixin-moesin homology) domain, a compact clover-leaf structure, binds partner proteins and mediates intramolecular regulatory interactions. Combined chemical cross-linking coupled to MS, small-angle X-ray scattering, computational docking and mutational analyses showed that the FAK FERM domain has a molecular cleft (~998 Å(2)) that interacts with sarcomeric myosin, resulting in FAK inhibition. Accordingly, mutations in a unique short amino acid sequence of the FERM myosin cleft, FP-1, impaired the interaction with myosin and enhanced FAK activity in cardiomyocytes. An FP-1 decoy peptide selectively inhibited myosin interaction and increased FAK activity, promoting cardiomyocyte hypertrophy through activation of the AKT-mammalian target of rapamycin pathway. Our findings uncover an inhibitory interaction between the FAK FERM domain and sarcomeric myosin that presents potential opportunities to modulate the cardiac hypertrophic response through changes in FAK activity.