The term harassment is often used to refer two contexts, the workplace and school, but not the legal system itself. Long drawn-out litigation in the Family Law Courts often produces a surreptitious phenomenon of violence toward one of the litigating parties, who become victims of the legal system itself. The aim of this study was to determine whether legal harassment could be detected and measured in the Spanish Justice System using an innovative Legal Harassment Scale (LHS). This hypothesis was substantiated by the data obtained using a new 32-item psychometric instrument with a global index: the LHS, consisting of four factors: Direct Aggression, Procedural Harassment, Personal Contempt, and Manipulation of Reality. The estimated reliability and validity of the LHS was satisfactory, both in terms of the global score, and for each of the four factors distributed along the normal curve. The results of this study are discussed in terms of the limitations of the study and in relation to future lines of research aimed at ensuring that the legal system respects and safeguards the rights of the parties involved in litigation, and that no party falls victim to legal harassment.

Glucagon is stored within the secretory granules of pancreatic alpha cells until stimuli trigger its release. The alpha cell secretory responses to the stimuli vary widely, possibly due to differences in experimental models or microenvironmental conditions. We hypothesized that the response of the alpha cell to various stimuli could be due to plasticity in the network of proteins that interact with glucagon within alpha cell secretory granules. We used tagged glucagon with Fc to pull out glucagon from the enriched preparation of secretory granules in α-TC1-6 cells. Isolation of secretory granules was validated by immunoisolation with Fc-glucagon and immunoblotting for organelle-specific proteins. Isolated enriched secretory granules were then used for affinity purification with Fc-glucagon followed by liquid chromatography/tandem mass spectrometry to identify secretory granule proteins that interact with glucagon. Proteomic analyses revealed a network of proteins containing glucose regulated protein 78 KDa (GRP78) and histone H4. The interaction between glucagon and the ER stress protein GRP78 and histone H4 was confirmed through co-immunoprecipitation of secretory granule lysates, and colocalization immunofluorescence confocal microscopy. Composition of the protein networks was altered at different glucose levels (25 vs. 5.5 mM) and in response to the paracrine inhibitors of glucagon secretion, GABA and insulin. siRNA-mediated silencing of a subset of these proteins revealed their involvement in glucagon secretion in α-TC1-6 cells. Therefore, our results show a novel and dynamic glucagon interactome within α-TC1-6 cell secretory granules. We suggest that variations in the alpha cell secretory response to stimuli may be governed by plasticity in the glucagon "interactome."

Peptidoglycan (PG) is an essential component of the cell envelope, maintaining bacterial cell shape and protecting it from bursting due to turgor pressure. The monoderm bacterium Staphylococcus aureus has a highly cross-linked PG, with ~90% of peptide stems participating in DD-cross-links and up to 15 peptide stems connected with each other. These cross-links are formed in transpeptidation reactions catalyzed by penicillin-binding proteins (PBPs) of classes A and B. Most S. aureus strains have three housekeeping PBPs with this function (PBP1, PBP2, and PBP3) but MRSA strains have acquired a third class B PBP, PBP2a, which is encoded by the mecA gene and required for the expression of high-level resistance to β-lactams. Another housekeeping PBP of S. aureus is PBP4, which belongs to the class C PBPs, and hence would be expected to have PG hydrolase (DD-carboxypeptidase or DD-endopeptidase) activity. However, previous works showed that, unexpectedly, PBP4 has transpeptidase activity that significantly contributes to both the high level of cross-linking in the PG of S. aureus and to the low level of β-lactam resistance in the absence of PBP2a. To gain insights into this unusual activity of PBP4, we studied by NMR spectroscopy its interaction in vitro with different substrates, including intact peptidoglycan, synthetic peptide stems, muropeptides, and long glycan chains with uncross-linked peptide stems. PBP4 showed no affinity for the complex, intact peptidoglycan or the smallest isolated peptide stems. Transpeptidase activity of PBP4 was verified with the disaccharide peptide subunits (muropeptides) in vitro, producing cyclic dimer and multimer products; these assays also showed a designed PBP4(S75C) nucleophile mutant to be inactive. Using this inactive but structurally highly similar variant, liquid-state NMR identified two interaction surfaces in close proximity to the central nucleophile position that can accommodate the potential donor and acceptor stems for the transpeptidation reaction. A PBP4:muropeptide model structure was built from these experimental restraints, which provides new mechanistic insights into mecA independent resistance to β-lactams in S. aureus.

Objectives. This systematic review aims to critically evaluate the efficacy of manual acupuncture for optic atrophy. Eight English and Chinese databases, including Cochrane Library, EMbase, PubMed, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, China Science and Technology Journal Database (VIP), and Chinese Biomedical Literature Database (CBM), as well as ongoing trials registered with the WHO International Clinical Trials Registry Platform, were searched to identify eligible randomized controlled trials (RCTs) studying manual acupuncture for optic atrophy compared to medication alone. The quality of evidence was assessed using Cochrane Collaboration's risk of bias tool. Meta-analysis was performed using Review Manager version 5.3. Nine studies were identified and included for meta-analysis. The meta-analysis showed significant differences in favor of manual acupuncture or manual acupuncture plus medication compared with medication alone in the following outcome measures: visual acuity (MD = 0.18, 95% CI [0.17, 0.20], P < 0.00001), mean sensitivity of visual field (MD = 2.11, 95% CI [1.90, 2.32], P < 0.00001), the latent period of P-VEP100 (MD = -6.80, 95% CI [-8.94, -4.66], P < 0.00001), the total effectiveness (264 eyes) (OR = 3.22, 95% CI [1.88, 5.51], P<0.0001), and the total effectiveness (344 participants) (OR = 4.29, 95% CI [2.56, 7.19], P < 0.00001). Despite statistical advantages of manual acupuncture in the literature, due to serious methodological flaws in study design, it cannot be concluded that manual acupuncture is more effective than medicine alone. It is essential that a properly controlled clinical trial is designed and controls are established to exclude placebo effects.

Atherosclerosis (AS) is a complicated arterial disease resulting from abnormal lipid deposition and inflammatory injury, which is attributed to Yin deficiency, accumulation of heat materials, and stasis of blood flow in Traditional Chinese Medicine (TCM) theory. Thus, according to TCM theory, the method of nourishing Yin (Yangyin), clearing away heat (Qingre), and promoting blood circulation (Huoxue) is a reasonable strategy, which has achieved remarkable clinical efficacy in the treatment of AS, but the mechanisms remain to be known. In this study, we evaluated the effects of Yangyin Qingre Huoxue Prescription (YQHP) on AS in ApoE-/- mice suffering from a high-fat diet and heat shock protein (HSP65) attack. YQHP regulated levels of blood lipids and inflammation-linked cytokines as well as Th17/Treg ratio in peripheral blood. Suppressed IL-6-p-STAT3 signaling and restored IL-2-p-STAT5 signaling in the presence of YQHP may partake in the regulation of Th17 and Treg differentiation. Moreover, YQHP modulated transcriptional levels of costimulator CD80 in aortas as well corresponding to the downregulation of GM-CSF in serum and CD3 expression in CD4+ T cells, which might indicate the potential of YQHP to regulate antigen presenting cells. All these effects eventually promoted the improvement of atherosclerotic lesions. In addition, YQHP promoted less monocyte infiltration in the liver and lower levels of AST, ALT, and AKP production than simvastatin. Conclusively, lipid-regulating and anti-inflammatory functions mediated by YQHP with lower hepatotoxicity than simvastatin hindered the progression of HSP65 aggravated AS in ApoE-/- mice, indicating the effectiveness of Yangyin Qingre Huoxue Method in the treatment of AS.

Objective. Panax ginseng is used widely for treatment of cardiovascular disorders in China. Ginsenoside Re is the main chemical component of P. ginseng. We aimed to investigate the protective effect of ginsenoside Re on isoproterenol-induced myocardial fibrosis and heart failure in rats. Methods. A model of myocardial fibrosis and heart failure was established by once-daily subcutaneous injection of isoproterenol (5 mg/kg/day) to rats for 7 days. Simultaneously, rats were orally administrated ginsenoside Re (5 or 20 mg/kg) or vehicle daily for 4 weeks. Results. Isoproterenol enhanced the heart weight, myocardial fibrosis, and hydroxyproline content in rat hearts. Ginsenoside Re inhibited (at least in part) the isoproterenol-induced increase in heart weight, myocardial fibrosis, and hydroxyproline content. Compared with the isoproterenol group, treatment with ginsenoside Re ameliorated changes in left ventricular systolic pressure, left ventricular end diastolic pressure, and the positive and negative maximal values of the first derivative of left ventricular pressure. Ginsenoside Re administration also resulted in decreased expression of transforming growth factor (TGF)-β1 in serum and decreased expression of Smad3 and collagen I in heart tissue. Conclusion. Ginsenoside Re can improve isoproterenol-induced myocardial fibrosis and heart failure by regulation of the TGF-β1/Smad3 pathway.

Piper carpunya Ruiz & Pav. (Piperaceae) is a perennial aromatic shrub of Amazonian area of Ecuador and Peru, belonging to the ethnomedicine of these countries. The traditional preparations of the crude drug (fresh leaves used topically as is, and dried leaves in infusions or decoctions) are known for anti-inflammatory, antiulcer, antidiarrheal, antiparasitic effects, and wound healing properties. In light of this traditional evidence, chemical composition (GC-MS) and biological activity, i.e., antioxidant, antifungal (yeast) capacities, and genotoxicity, of Amazonian P. carpunya leaf essential oil (EO) have been investigated in order to valorize some of the putative ethnomedical effects. The EO was obtained through steam distillation of fresh leaves (yield: 7.6 g/kg [0.76%]; refractive index at 20°C: 1.49; density: 0.928 g/mL). Chemical characterization performed through GC-MS evidenced the presence of 21 compounds (96.2% of the total). The most abundant constituents were piperitone (26.2%), limonene (9.5%), elemicin (7.2%), and β-phellandrene (5.6%). In vitro DPPH antioxidant assay showed a weak radical scavenging ability (IC50) if compared to positive control. Low bioactivity of the EO was also demonstrated against yeast, but it showed an interesting synergistic activity (FIC index of EO+fluconazole) against Candida sp. strains. Ames test evidenced the safety of the EO concerning genotoxicity.

Predicting disease progression in chronic lymphocytic leukemia (CLL) remains challenging particularly in patients with Rai Stage 0/I disease that have an unmutated immunoglobulin heavy chain variable region (UM IGHV). Even though patients with UM IGHV have a poor prognosis and generally require earlier treatment, not all UM IGHV patients experience more rapid disease progression with some remaining treatment free for many years. This observation suggests biologic characteristics other than known prognostic factors influence disease progression. Alterations in long non-coding RNA (lncRNA) expression levels have been implicated in diagnosis and prognosis of various cancers, however, their role in disease progression of early Rai stage UM CLL is unknown. Here we use microarray analysis to compare lncRNA and mRNA profiles of Rai 0/I UM IGHV patients who progressed in <2 years relative to patients who had not progressed for >5 years. Over 1,300 lncRNAs and 940 mRNAs were differentially expressed (fold change ≥ 2.0; p-value ≤ 0.05). Of interest, the differentially expressed lncRNAs T204050, NR_002947, and uc.436+, have known associated genes that have been linked to CLL. Thus, our study reveals differentially expressed lncRNAs in progressive early stage CLL requiring therapy versus indolent early Rai stage UM CLL. These lncRNAs have the potential to impact relevant biological processes and pathways that influence clinical outcome in CLL.

Steroids promote the myelination and regeneration in the peripheral nervous system. Whereas, little is known about the inducing effects by which the hormones exert their effects on Schwann cells differentiation. This could be revealed by the expression of Schwann cell markers in adipose-derived stem cells (ADSCs). The purpose of this study was to present the effects of progesterone and 17 β-estradiol on the Schwann cell markers in rat ADSCs. The mesenchymal stem cell markers (CD73, and CD90) were assayed by flow cytometry. Rat ADSCs were sequentially treated with β-mercaptoethanol, and all-trans-retinoic acid, followed by a mixture of basic fibrobroblast growth factor, platelet-derived growth factor, forskolin and heregulin. In experimental groups, forskolin and heregulin were substituted by progesterone and 17 β-estradiol. After induction, the expression of Schwann cell markers P0, and S-100 and the cellular immunocytochemical staining positive rate of anti-S100 and anti-glial fibrillary acidic protein (GFAP) antibodies were compared in the experimental and control groups. Progesterone and 17 β-estradiol triggered P0 and S-100 genes expression and induced a cellular immunocytochemical staining positive rate of S-100 and GFAP in rats ADSCs. Progesterone induced these changes stronger than 17 β-estradiol. Thus, progesterone may induce rat ADSCs toward Schwann-like cells by expression of Schwann cell markers and is more potent than 17 β-estradiol in the expression of these markers.

Uveitis is a major cause of vision loss. Methotrexate (MTX) has been widely used in uveitis due to its relatively safe profile. The purpose of this study was to evaluate the effects of two different dosages of MTX via intra-vitreal administration for treatment of endotoxin induced uveitis (EIU) in an experimental model. Thirty-five healthy rabbits were randomly divided into four groups and all animals were tolerated intra-vitreal injections. The first group received normal saline (NS), the second group received normal saline plus Salmonella typhimurium lipopolysaccharide endotoxin (LPS), (NS+LPS), the third group received 400 μg MTX plus LPS (LPS+MTX 400) and the fourth group received 800 μg MTX plus LPS (LPS+MTX 800). Intra-ocular inflammation was evaluated by clinical examination scoring during 7 post-injection days and histopathological examination at the end of study. Kruskal-Wallis and Mann-Whitney U tests were used to compare the histopathological and clinical scores. According to the clinical examinations, all groups demonstrated higher uveitis score than group 1 on first post-injection day. Also, groups 2 and 3 showed greater uveitis score than group 4. On the third, fifth and seventh post-injection days, clinical uveitis score in groups 2, 3 and 4 was significantly higher than group 1. The mean histopathological inflammation intensity scores in groups 2, 3 and 4 were significantly higher than group 1. Single intra-vitreal injection of 400 μg and 800 μg of MTX did not show significant anti-inflammatory effects on EIU in rabbits.

The aim of the present study was to investigate the diagnostic evaluation of milk lactate dehydrogenase (mLDH) and alkaline phosphatase (mALP) activities by receiver operating characteristic (ROC) analysis curve in early lactation of ewes with subclinical mastitis (SCM) and determine the correlation between number of somatic cell count (SCC) and mLDH and mALP activities. A total of 196 udder half milk samples were collected within the first 6 weeks of lambing. The SCM was determined by positive milk bacterial culture and positive California mastitis test (CMT); SCC was determined by fossomatic method and enzyme activities were determined spectrophotometrically. The mLDH and mALP of SCM cases were positively correlated with SCC values. Values of mLDH, mALP and SCC were significantly higher in SCM than non-SCM udder halves. The optimum cut-off points of mLDH and mALP activities for SCM diagnosis were determined at 203.61 (U L-1) and 329.84 (U L-1), respectively. In conclusion, SCC has positive correlation with mALP and mLDH activities in SCM ewes and mLDH and mALP activities could be considered as reliable indicators for intra-mammary inflammation diagnosis.

Barberry fruit is consumed in different forms including dried fruit, juice, jam and marmalade in Iran. This fruit is also used as a food additive (flavoring and colorant) in soup and rice dishes. In present study, antioxidant activities of acetone, ethanol and water (infusion and decoction) extracts of barberry (Berberis vulgaris) fruit were investigated using 2,2-azinobis-3-ethylbenzothiazoline-6-sulphonic acid (ABTS), 2,2-diphenyl-1-picrylhydrazyl (DPPH) and reducing power methods. Total phenolic contents of the extracts were also estimated using Folin-Ciocalteu assay. In ABTS assay, acetone and ethanol extracts showed the highest radical scavenging activity, while in DPPH and reducing power methods, acetone extract and decoction exhibited the strongest antioxidant activity. Meanwhile, the antioxidant potential of water extracts increased with increasing heating time (antioxidant activity of decoction was higher than that of infusion). The highest total phenolic content was found in the acetone extract (92.75 mg GAE per g). It was concluded that the acetone extract and decoction of barberry fruit can be used as an effective natural antioxidant in food industry.

A polycephalic larva of Taeniidae family isolated from abdominal cavity of a great gerbil (Rhombomys opimus) from Golestan province, northern Iran, was subjected to molecular analysis. Genomic DNA from the larva was obtained using a DNA extraction tissue kit. Polymerase chain reaction was performed for amplification of the partial 12S rRNA, cytochrome c oxidase subunit 1 (cox1) and NADH dehydrogenase 1 (nad1) mitochondrial genes. BLAST analysis of DNA sequencing indicated 99.00% homology in 12S rRNA and cox1 genes and 98.00% homology in nad1 gene with Hydatigera krepkogorski (accession No. AB731762). The sequences of current isolate were deposited in GenBank by accession Nos. MF281971, MF281972 and MF281973 for 12 SrRNA, cox1 and nad1 genes, respectively. This study was the first report of molecular characterization of H. krepkogorski from Iran. Isolation and characterization of the adult stage from definitive host will help to better clarify incomplete life cycle and morphology data of this species in the world.

The ionic assembly of oppositely charged polyelectrolyte-surfactant complexes (PESCs) is often done with the aim of constructing more functional colloids, for instance as advanced delivery systems. However, PESCs are often not easily loaded with a solubilisate due to intrinsic restrictions of such complexes. This question was addressed from a different starting point: by employing microemulsion droplets as heavily loaded surfactant systems and thereby avoiding potential solubilisation limitations from the beginning. We investigated mixtures of cationic oil-in-water (O/W) microemulsion droplets and oppositely charged sodium polyacrylate (NaPA) and determined structure and phase behaviour as a function of the mixing ratio for different droplet sizes and different M w (NaPA). Around an equimolar charge ratio an extended precipitate region is present, which becomes wider for larger droplets and with increasing M w of the NaPA. Static and dynamic light scattering (SLS and DLS) and small-angle neutron scattering (SANS) show the formation of one-dimensional arrangements of microemulsion droplets for polyelectrolyte excess, which become more elongated with increasing M w (NaPA) and less so with increasing NaPA excess. What is interesting is a marked sensitivity to ionic strength, where already a modest increase to ∼20 mM leads to a dissolution of the complexes. This work shows that polyelectrolyte/microemulsion complexes (PEMECs) are structurally very versatile hybrid systems, combining the high solubilisate loading of microemulsions with the larger-scale structuring induced by the polymer, thereby markedly extending the concept of conventional PESCs. This type of system has not been described before and is highly promising for future applications where high payloads are to be formulated.

Hyposmia is one of the earliest and the most common symptoms in Parkinson's disease (PD). The benefits of hydrogen water on motor deficits have been reported in animal PD models and PD patients, but the effects of hydrogen gas on PD patients have not been studied. We evaluated the effect of inhalation of hydrogen gas on olfactory function, non-motor symptoms, activities of daily living, and urinary 8-hydroxy-2'-deoxyguanine (8-OHdG) levels by a randomized, double-blinded, placebo-controlled, crossover trial with an 8-week washout period in 20 patients with PD. Patients inhaled either ~1.2-1.4% hydrogen-air mixture or placebo for 10 minutes twice a day for 4 weeks. Inhalation of low dose hydrogen did not significantly influence the PD clinical parameters, but it did increase urinary 8-OHdG levels by 16%. This increase in 8-OHdG is markedly less than the over 300% increase in diabetes, and is more comparable to the increase after a bout of strenuous exercise. Although increased reactive oxygen species is often associated with toxicity and disease, they also play essential roles in mediating cytoprotective cellular adaptations in a process known as hormesis. Increases of oxidative stress by hydrogen have been previously reported, along with its ability to activate the Nrf2, NF-κB pathways, and heat shock responses. Although we did not observe any beneficial effect of hydrogen in our short trial, we propose that the increased 8-OHdG and other reported stress responses from hydrogen may indicate that its beneficial effects are partly or largely mediated by hormetic mechanisms. The study was approved by the ethics review committee of Nagoya University Graduate School of Medicine (approval number 2015-0295). The clinical trial was registered at the University Hospital Medical Information Network (identifier UMIN000019082).

It has been confirmed that inflammation plays an important role in the pathogenesis of ischemic stroke. The polarization of microglia as an important participant in the inflammation following stroke is also found to be involved in stroke. This study aimed to investigate the effects of hydrogen gas on the polarization of macrophages/microglia in vitro. Raw264.7 cells were treated with lipopolysaccharides and then exposed to hydrogen. The microglia were treated with the supernatant from oxygen and glucose deprivation-treated neurons and then exposed to hydrogen. The phenotypes of Raw 264.7 cells and microglia were determined by flow cytometry, and cell morphology was observed. Results showed lipopolysaccharides significantly increased the M1 macrophages, and the supernatant from oxygen and glucose deprivation-treated neurons dramatically elevated the proportion of M1 microglia, but both treatments had little influence on the M2 cells. In addition, hydrogen treatment significantly inhibited the increase in M1 cells, but had no influence on M2 ones. Our findings suggest that the neuroprotection of hydrogen may be related to its regulation of microglia in the nervous system after stroke.

In Japan, alkaline electrolyzed water (AEW) apparatus have been approved as a medical device. And for the patients with gastrointestinal symptoms, drinking AEW has been found to be effective in relieving gastrointestinal symptoms. But some users of AEW apparatus do not have abdominal indefinite complaint. Little attention has been given to the benefit for the users which have no abdominal indefinite complaint. The object of this study is to evaluate the effect on health, including gastrointestinal symptoms, when a person without abdominal indefinite complaint, etc., drinks AEW on a daily basis. A double-blind, randomized controlled trial has been designed. Four-week period of everyday water drinking, PW drinking group: drink purified tap water as a placebo, AEW drinking group: drink alkaline electrolyzed water which made by electrolysis of purified tap water. Before the experiment and after the 4-week period of water drinking, Blood tests, physical fitness evaluations, and questionnaire evaluations is conducted. In this study, we did not specifically select patients with gastrointestinal symptoms. Sufficiently clear effect could not be confirmed. But the stools were more normal, and, as shown in the previous report, that drinking AEW is considered to contribute to intestinal normalization. In addition, when drinking AEW, a high proportion of the respondents said that they felt they were able to sleep soundly, and the proportion of subjects who answered that they felt good when awakening increased. The effect of reducing oxidative stress, thus allowing for improved sleep, was exhibited by drinking AEW containing hydrogen, which is considered to be an antioxidant substance. This research were approved by the Ethics Committee of the Osaka City University Graduate School of Medicine (No. 837) and were registered in the University Hospital Medical Information Network (UMIN) Clinical Trials Registry (UMIN ID: UMIN000031800) on March 22, 2018.

A 58-year-old female was diagnosed with Alzheimer's dementia (AD) which was rapidly progressive in the 8 months prior to initiation of hyperbaric oxygen therapy (HBOT). 18Fluorodeoxyglucose (18FDG) positron emission tomography (PET) brain imaging demonstrated global and typical metabolic deficits in AD (posterior temporal-parietal watershed and cingulate areas). An 8-week course of HBOT reversed the patient's symptomatic decline. Repeat PET imaging demonstrated a corresponding 6.5-38% regional and global increase in brain metabolism, including increased metabolism in the typical AD diagnostic areas of the brain. Continued HBOT in conjunction with standard pharmacotherapy maintained the patient's symptomatic level of function over an ensuing 22 months. This is the first reported case of simultaneous HBOT-induced symptomatic and 18FDG PET documented improvement of brain metabolism in AD and suggests an effect on global pathology in AD.

Bone marrow-derived multipotent adult progenitor cells (MAPCs) are adult allogeneic adherent stem cells currently investigated clinically for use in acute respiratory distress syndrome (ARDS). To date, there is no agreement on which is the best method for stem cells delivery in ARDS. Here, we compared the efficacy of two different methods of administration and biodistribution of MAPC for the treatment of ARDS in a sheep model.

Latinos constitute a hard-to-reach minority population in Iowa.