Distinct chromium removal mechanisms by iron-modified biochar under varying pH: Role of iron and chromium speciation.
Iron-modified biochar (Fe-biochar) has been widely developed to attenuate Cr(VI) pollution in both acid and alkaline environments. However, there are few comprehensive studies on how the iron speciation in Fe-biochar and chromium speciation in solution influencing the removal of Cr(VI) and Cr(III) under varying pH. Here, multiple Fe-biochar containing Fe3O4 or Fe(0) were prepared and applied to remove aqueous Cr(VI). Kinetics and isotherms suggested that all Fe-biochar could efficiently remove Cr(VI) and Cr(III) via adsorption-reduction-adsorption. The Fe3O4-biochar immobilized Cr(III) by forming FeCr2O4, while amorphous Fe-Cr coprecipitate and Cr(OH)3 was formed when using Fe(0)-biochar. Density functional theory (DFT) analysis further indicated that pH increase caused more negative adsorption energies between Fe(0)-biochar and the pH-dependent Cr(VI)/Cr(III) species. Consequently, the adsorption and immobilization of Cr(VI) and Cr(III) species by Fe(0)-biochar was more favored at higher pH. In comparison, Fe3O4-biochar exhibited weaker adsorption abilities for Cr(VI) and Cr(III), which were in consistent with their less negative adsorption energies. Nonetheless, Fe(0)-biochar merely reduced ∼70% of adsorbed Cr(VI), while ∼90% of adsorbed Cr(VI) was reduced by Fe3O4-biochar. These results unveiled the importance of iron and chromium speciation for chromium removal under varying pH, and might guide the application-oriented design of multifunctional Fe-biochar for broad environmental remediation.


Numerical scheme for the modal method based on subsectional Gegenbauer polynomial expansion: application to biperiodic binary grating.
The modal method based on Gegenbauer polynomials (MMGE) is extended to the case of bidimensional binary gratings. A new concept of modified polynomials is introduced in order to take into account boundary conditions and also to make the method more flexible in use. In the previous versions of MMGE, an undersized matrix relation is obtained by solving Maxwell's equations, and the boundary conditions complement this undersized system. In the current work, contrary to this previous version of the MMGE, boundary conditions are incorporated into the definition of a new basis of polynomial functions, which are adapted to the boundary value problem of interest. Results are successfully compared for both metallic and dielectric structures to those obtained from the modal method based on Fourier expansion (MMFE) and MMFE with adaptative spatial resolution.


Enhancing the anterograde movement of HRP to label sparse neuronal projections.
By combining techniques designed to increase the amount of horseradish peroxidase (HRP) available for transport and to improve the sensitivity of the reaction for detecting HRP, we have produced an anterograde HRP technique suitable for labeling sparse efferent projections. The efficacy of this light, microscopic technique was demonstrated by lebeling the hippocampal commissural and crossed temporo-ammonic projections to the dentate gyrus of the rat.


[Identification of anomalous coronary arteries and their anatomic course by multidetector computed tomography coronarography. A retrospective registry].
The coronary anomalies are generally asymptomatic and rare. However, their potential complications are serious and mainly represented by the risk of sudden death. The coronarography appears insufficient to carry out the complete assessment of these anomalies, and in particular to study the arterial course. The endpoint of our series is to evaluate the interest of the coronary computed tomography (CT) in this indication. We report the results of a 16-slice coronary-CT monocentric retrospective series among 12 patients presenting coronary anomalies diagnosed in coronarography. Coronary-CT has confirmed the diagnosis, specified the coronary course and the relation with the great vessels in 100% of the cases. Multislice coronary-CT seems an examination of choice for the diagnosis and the presurgical assessment of the coronary aberrations, like for the distinction of the benign and malign forms. Its effectiveness and its "non-invasive" character are strong arguments to include it in the assessment of syncopes linked to effort in the young adult.


HIV prevention among serodifferent couples: postures and difficulties in Lomé (Togo)
The protocol for the management of HIV-positive couples in Togo recommends the systematic use of condoms as the only means of preventing the sexual transmission of HIV. Nevertheless, the incidence of HIV in Togolese serodifferent couples remains high. The aim of the article is to identify barriers to compliance with official guidelines for the prevention of sexual transmission of HIV among serodifferent couples in Lomé. The study was qualitative. A literature review was conducted. 48 semi-structured interviews were conducted with 36 PLHIV (10 men and 26 women), 8 health care providers and 4 religious leaders. The religious leaders have a spiritual understanding of HIV infection. They are unfavorable to the use of condoms by couples and advise against it. HIV-positive couples experience psychological difficulties and fear the contamination of the HIV-negative partner, which negatively influences their sexuality. Very few of the couples interviewed respect the protocol of systematic condom use. The reasons for this are reluctance based on psycho-affective barriers, supply difficulties, technical difficulties, religious prohibitions and the desire for a child. The analysis show significant difficulties for couples in complying with the medical prescriptions in Togo, namely the systematic use of condoms. The analysis of these difficulties makes it possible to highlight on the one hand, the obstacles inherent in the postures of couples and the influence of their socio-cultural environment, and on the other hand, those related to the inadequacies of the offer of HIV services. For better protection, it would be judicious to accentuate their therapeutic education in order to improve and maintain a high level of therapeutic compliance by the seropositive partner.


Treatment of panic disorder via the Internet: a randomized trial of CBT vs. applied relaxation.
A randomized trial was conducted of two different self-help programs for panic disorder (PD) on the Internet. After confirming the PD-diagnosis with an in-person structured clinical interview for DSM-IV (SCID) interview 22 participants were randomized to either applied relaxation (AR) or a multimodal treatment package based on cognitive behavioral therapy (CBT). Overall, the results suggest that Internet-administered self-help plus minimal therapist contact via e-mail has a significant medium to large effect (Cohen's d=0.71 for AR and d=0.42 for CBT). The results from this study generally provide evidence to support the continued use and development of Internet-distributed self-help programs.


Proper Sequencing of Treatment for Castrate Resistant Prostate Cancer.
Although androgen deprivation therapy results in clinical and/or disease biochemical remission, disease will ultimately progress from androgen sensitivity to a castration resistant status. Therapeutic options for men with metastatic castration resistant prostate cancer have changed dramatically in the last decade. We review potential sequencing of these therapeutic options based on the currently available published literature. Since 2010 the Food and Drug Administration has approved 5 new castrate resistant prostate cancer therapies, all with proven survival benefit. These breakthrough therapies and their impact on the disease landscape prompted the AUA in 2013 to establish its first castrate resistant prostate cancer guideline, creating a framework for urologists to better understand their expanded role in the treatment of men with advanced prostate cancer. Currently, 5 new agents, sipuleucel-T, cabazitaxel, abiraterone, enzalutamide and radium-223 dichloride, have been approved by the Food and Drug Administration to treat castrate resistant prostate cancer on the basis of randomized clinical trials. These approvals, and other anticipated novel therapies, highlight the need for the AUA guidelines to be updated regularly to inform the clinician about this rapidly evolving disease state and the importance of adopting these new therapies. In less than 3 years multiple new therapeutics have been approved for the treatment of metastatic castration resistant prostate cancer. The mechanisms of action as well as the modes of delivery are largely unique. Recognizing the sequencing order for these new therapies requires an understanding of the published peer reviewed literature as well as clinical judgment and experience. This article provides a review of the literature as well as guidance to assist clinicians who desire to treat metastatic castrate resistant prostate cancer.


Vasopressin excites neurones located in the dorsal cochlear nucleus of the guinea-pig brainstem.
The effect of arginine vasopressin (AVP) on neurones in the dorsal cochlear nucleus (DCN) of young guinea-pigs of either sex was investigated in brainstem slices. Most impaled neurones fired in a regular manner, either spontaneously or following a depolarizing current injection. AVP, at concentrations of 10-1000 nM, excited 19/19 neurones from male and 16/19 neurones from female animals. This effect of AVP was concentration-dependent and could be mimicked by the V1 agonist [Phe2,Orn8]VT. Oxytocin was less potent than AVP and a selective V2 agonist, deamino-DAVP, was without effect. Thus, a class of DCN neurones is probably endowed with functional V1 vasopressin receptors. By making use of an antibody raised against the vasopressin-related glycopeptide, dense AVP-like immunoreactivity was found in the DCN of young animals of either sex.


A mitogenic factor from rat muscle.
A growth-promoting polypeptide has been purified about 1950-fold from rat abdominal muscle by gel chromatography, isoelectric-focusing (IEF) and reverse phase high pressure liquid chromatographic (RP-HPLC) techniques. This factor is an acidic protein with an isoelectric point (pI) of 3.4 and a mol. wt of 12 kDa when run on SDS-polyacrylamide gels under reducing conditions. It is acid and heat-stable but is sensitive to reducing agent and protease action. It stimulates [3H]thymidine incorporation in NRK-49F and NIH 3T3 cells and induces soft agar colony formation of NIH 3T3 cells. The muscle-derived mitogen appears to differ from other known growth factors (GFs) in its physico-chemical properties.


Development of a growth inhibition test with the marine and brackish water red alga Ceramium tenuicorne.
The marine red macroalga Ceramium tenuicorne is cosmopolitan and naturally found in both brackish and marine waters. A growth inhibition test with this species can be carried out in salinities from 4 per thousand to 32 per thousand. The species is easily held in culture in the laboratory and the test can be performed in a completely defined medium. The robustness of the method is good with a CV of 14.6% of the controls. The EC calculations can be performed on linear regression on the length data. EC50 values of repetitive tests for zinc (20-33 microg Zn(2+)/l in 7 per thousand and 32-61 microg Zn(2+)/l in 20 per thousand) and copper (1.9-3.8 Cu(2+)/l in 7 per thousand and 7.9-13 Cu(2+)/l in 20 per thousand) show high sensitivity. This test is a good complement to any test battery with the purpose of estimating the hazard of substances to the brackish and marine environment.


Review article: exposure to microbes and risk of coeliac disease.
Coeliac disease is an immune-mediated intestinal disease characterised by lifelong intolerance to dietary gluten in genetically predisposed individuals. Microbial factors including infections or bacterial microbiota have long been suspected to be involved in the aetiology, but the scientific literature on the topic is scattered and heterogeneous. To review human observational studies on microbes and coeliac disease METHODS: We identified 135 publications judged relevant. Most studies were cross-sectional, and prone to reverse causation and other biases. Only a few were prospective. Cohort studies and longitudinal studies that have sampled biological specimens before disease onset are emphasised in the review. Infections during early childhood were associated with an increased risk of subsequent coeliac disease in nine studies , whereas maternal infections during pregnancy did not show a clear association. For the most frequently studied microbial factors, some evidence for an association was found, including Helicobacter pylori (four out of 16 studies), adenovirus (two out of nine studies) and enterovirus (two out of six studies). Rotavirus infections have been associated with disease development, and rotavirus vaccination may reduce the risk. Among the many studies of gut microbiota, most were cross-sectional and, therefore, potentially influenced by reverse causation. Only two smaller prospective case-control studies with sampling before disease onset were identified; they reported inconsistent findings regarding the faecal microbiome. Several microbes are potentially linked to coeliac disease. As microbial factors are amenable to interventions, larger prospective studies are still warranted.


Interocular transfer in individuals with strabismic amblyopia; a cautionary note.
Interocular transfer of the adaptation after effect was measured and correlated with residual binocular function for two strabismic amblyopes who represent different types of neural loss. The results indicate that for these two subjects there is paradoxical correlation between efficacy of interocular transfer and residual binocular function.


Barriers to the uptake of cervical cancer services and attitudes towards adopting new interventions in Peru.
Cervical cancer mortality is high among Peruvian women of reproductive age. Understanding barriers and facilitators of cervical cancer screening and treatment could facilitate development of contextually-relevant interventions to reduce cervical cancer incidence and mortality. From April to October 2019, we conducted a cross-sectional survey with 22 medical personnel and administrative staff from Liga Contra el Cancer, in Lima, Peru. The survey included structured and open-ended questions about participants' roles in cervical cancer prevention and treatment, perceptions of women's barriers and facilitators for getting screened and/or treated for cervical cancer, as well as attitudes towards adopting new cervical cancer interventions. For structured questions, the frequency of responses for each question was calculated. For responses to open-ended questions, content analysis was used to summarize common themes. Our data suggest that the relative importance and nature of barriers that Peruvian women face are different for cervical cancer screening compared to treatment. In particular, participants mentioned financial concerns as the primary barrier to treatment and a lack of knowledge or awareness of human papillomavirus and/or cervical cancer as the primary barrier to screening uptake among women. Participants reported high willingness to adopt new interventions or strategies related to cervical cancer. Building greater awareness about benefits of cervical cancer screening among women, and reducing financial and geographic barriers to treatment may help improve screening rates, decrease late-stage diagnosis and reduce mortality in women who have a pre-cancer diagnosis, respectively. Further studies are needed to generalize study findings to settings other than Lima, Peru.


Selective nano-thermal therapy of human retinoblastoma in retinal laser surgery.
In this research, an experimental validated predictive finite element model of a cancerous human eye is developed to investigate how the tumor cells in retinoblastoma can be selectively damaged in the course of laser irradiation. In the computational modeling, the tumor is assumed to be in the initial growth stages and located in the macular zone. The statistical calculations testify that an 8.5% improvement in our estimation of the experimental temperature inside the normal human eye compared to those provided by the previous model has been achieved. Under the surgical conditions, the at-risk regions are determined, and the thermal responses of the tissue to various intrinsic and operating factors are obtained and discussed. Our findings indicate that, in the same amount of exposure time, introducing biodegradable nanoparticles in a concentration of 0.2 into the tumor tissue can increase the lethal zone area by 51 percent, and could plays an effective role in surviving of corneal injury.


Role of organ transplantation in the treatment of malignancies: hepatocellular carcinoma as the most common tumour treated with transplantation.
There are only few malignant tumours where organ transplantation is the treatment of choice. Transplantation can be considered individually in certain lung carcinomas, unresectable heart tumours, cholangiocellular carcinoma and Klatskin tumour. It is acceptable in unresectable chemosensitive hepatoblastoma, epitheloid haemangioendothelioma, liver metastasis of neuroendocrine tumours and as the most common indication, the early hepatocellular carcinoma (HCC) in cirrhotic liver. Results of liver transplantation (LT) for HCC according to Milan criteria as a "gold standard" are excellent. Time of LT has a great influence on the results. While patients are on waiting list, locoregional therapies may help prevent tumour progress. Living donor LT is an acceptable treatment of HCC. The greatest experience with this procedure is in Asia. Despite the favourable results, LT as the treatment of HCC is debated and raises several questions: regarding indication and expectable outcome. Milan criteria seem to answer this questions although they are too strict. The number and size of HCC foci per se is not sufficient predictor of eligibility to transplantation and for prognosis. Majority of the prognostic factors can be evaluated only after transplantation with pathological examination of HCC. Aim of the present research is to find prognostic factors that are characteristic of biological behaviour of HCC, which can be detected before LT in order to select patients who have the greatest benefit from LT. Re-definition of eligibility criteria is an actual question; an international consensus based on additional prospective studies is required for the "new" recommendation.


[Eosinophilic infiltrate with reference to Toxocara canis. Apropos of a case in an adult].
Larva migrans syndromes are rare affections that occur mainly in young children. The usual parasite involved is Toxocara canis, its presence in humans leading to encystment of the larvae and an eosinophilic granulomatous reaction. A case of an adult with this affection is reported, and clinical aspects and diagnostic and therapeutic problems discussed.


Impact of fat on the apparent T1 value of the liver: assessment by water-only derived T1 mapping.
To determine the impact of fat on the apparent T1 value of the liver using water-only derived T1 mapping. 3-T MRI included 2D Look-Locker T1 mapping and proton density fat fraction (PDFF) mapping. T1 values of the liver were compared among T1 maps obtained by in-phase (IP), opposed-phase (OP), and Dixon water sequences using paired t-test. The correlation between T1 values of the liver on each T1 map and PDFF was assessed using Spearman correlation coefficient. The absolute differences between T1 value of the liver on Dixon water images and that on IP or OP images were also correlated with PDFF. One hundred sixty-two patients (median age, 70 [range, 24-91] years, 90 men) were retrospectively evaluated. The T1 values of the liver on each T1 map were significantly different (p < 0.001). The T1 value of the liver on IP images was significantly negatively correlated with PDFF (r = - 0.438), while the T1 value of the liver on OP images was slightly positively correlated with PDFF (r = 0.164). The T1 value of the liver on Dixon water images was slightly negatively correlated with PDFF (r = - 0.171). The absolute differences between T1 value of the liver on Dixon water images and that on IP or OP images were significantly correlated with PDFF (r = 0.606, 0.722; p < 0.001). Fat correction for the apparent T1 value by water-only derived T1 maps will be helpful for accurately evaluating the T1 value of the liver. Fat-corrected T1 mapping of the liver with the water component only obtained from the 2D Dixon Look-Locker sequence could be useful for accurately evaluating the T1 value of the liver without the impact of fat in daily clinical practice. • The T1 values of the liver on the conventional T1 maps are significantly affected by the presence of fat. • The apparent T1 value of the liver on water-only derived T1 maps would be slightly impacted by the presence of fat. • Fat correction for the apparent T1 values is necessary for the accurate assessment of the T1 values of the liver.


Comparing Pharmacological Modulation of Sensory Gating in Healthy Humans and Rats: The Effects of Reboxetine and Haloperidol.
Sensory gating is the brain's ability to filter out irrelevant information before it reaches high levels of conscious processing. In the current study we aimed to investigate the involvement of the noradrenergic and dopaminergic neurotransmitter systems in sensory gating. Furthermore, we investigated cross-species reliability by comparing effects in both healthy humans and rats, while keeping all experimental conditions as similar as possible between the species. The design of the human experiment (n=21) was a double-blind, placebo-controlled, cross-over study where sensory gating was assessed following a dose of either reboxetine (8 mg), haloperidol (2 mg), their combination or placebo at four separate visits. Similarly in the animal experiment sensory gating was assessed in rats, (n=22) following a dose of reboxetine (2 mg/kg), haloperidol (0.08 mg/kg), their combination or placebo. The sensory gating paradigms in both experiments were identical. In humans, we found significantly reduced P50 suppression following separate administration of reboxetine or haloperidol, while their combined administration did not reach statistical significance compared with placebo. In the rats, we found a similar significant reduction of sensory gating (N40) following treatment with haloperidol and the combination of haloperidol and reboxetine, but not with separate reboxetine treatment, compared with placebo. Our study indicates that even when experimental conditions are kept as similar as possible, direct human to rat cross-species translation of pharmacological effects on sensory gating is challenging, which calls for more focussed research in this important translational area.


Phosphorothiolation of Aryl Boronic Acids Using P(O)H Compounds and Elemental Sulfur.
The first multicomponent reaction (MCR) involving aryl boronic acids, elemental sulfur, and P(O)H compounds is presented. It proceeds with excellent yields and provides an attractive approach for the construction of valuable S-aryl phosphorothioates and S-aryl phosphorodithioates using a one-step strategy. Moreover, this method can be easily adapted to large-scale preparation.


Mother-child and siblings' mediated learning strategies in families with and without children with intellectual disability.
The objectives of the research were to study differences in Mediated Learning Experience (MLE) strategies between mothers and their children in families with intellectually disabled and typically developing children and the cross-generation transmission of MLE strategies. Dyads of mother-child and siblings were observed interacting in free-play and teaching situations and their mediation strategies were analyzed by the Observation of Mediation Interaction scale. The child in the mother-child interaction was the older sibling in the siblings' interaction. Siblings samples were composed of two main groups: where the younger sibling (a) had an intellectual disability (ID, n = 25), or typically developing sibling dyads matched on (b) difference in mental age (TDM, n = 25) and (c) difference in chronological age (TDC, n = 25). The mediation strategies of older-younger siblings were compared to that of mother-child (with older sibling). The findings showed that siblings demonstrated higher level of MLE strategies than mothers in the ID group as compared with the two TD groups and that there is a cross-generation transmission of MLE strategies after controlling variables of group, mothers' years of education, level of occupation, and level of religiosity. The findings implications are related to the central role of siblings in families with a child with ID and working with families to enhance children's cognitive development.


Isolation of a novel thermophilic Campylobacter from cases of spotty liver disease in laying hens and experimental reproduction of infection and microscopic pathology.
The condition known as spotty liver disease or spotty liver syndrome can cause significant mortality in free range laying hen flocks. It has been described in Europe and Australia but the aetiology has not been established. There are similarities between spotty liver disease and avian vibrionic hepatitis, a condition which was reported in the 1950s. A Vibrio-like organism was suspected to be the cause of avian vibrionic hepatitis, although this organism was never fully characterised. We report the isolation of a novel Campylobacter from five separate outbreaks of spotty liver disease. The conditions required for culture, the growth characteristics, electron microscopical morphology and results of the phenotypic tests used in the identification of this novel Campylobacter sp. are described. The novel Campylobacter is slow growing and fastidious and does not grow on media routinely used for isolating Campylobacter sp. The morphology is typical for a Campylobacter sp. and phenotypic tests and a duplex real time PCR test differentiate the novel Campylobacter from other members of the genus. 16S rRNA analysis of 19 isolates showed an identical sequence which appears to represent a hitherto unknown sub lineage within the genus Campylobacter. Experimental intraperitoneal infection of four week old SPF chickens produced microscopic liver pathology indistinguishable from natural disease and the novel Campylobacter was recovered from the experimentally infected chicks. The isolates described appear to be a possible causal organism for spotty liver disease.


The quality of energy- and macronutrient-balanced diets regulates host susceptibility to influenza in mice.
Modulation of individual macronutrients or caloric density is known to regulate host resistance to infection in mice. However, the impact of diet composition, independent of macronutrient and energy content, on infection susceptibility is unclear. We show that two laboratory rodent diets, widely used as standard animal feeds and experimental controls, display distinct abilities in supporting mice during influenza infection. Mice placed on the highly processed AIN93G showed increased mortality to infection compared with those on a grain-based chow diet, suggesting a detrimental role for highly processed food in host defense. We further demonstrate that the heightened susceptibility of AIN93G-fed mice was associated with the failure in homeostasis restoration mediated by the cytokine interferon (IFN)-γ. Our findings show that diet composition calibrates host survival threshold by regulating adaptive homeostasis and highlights a pivotal role for extrinsic signals in host phenotype and outcome of host-pathogen interaction.


Implementation of the Modified Canadian C-Spine Rule by Paramedics.
The Canadian C-spine rule was modified and validated for use by the paramedics in a multicenter study where patients were assessed with the Canadian C-spine rule yet all transported with immobilization. This study evaluated the clinical impact of the modified Canadian C-spine rule when implemented by paramedics. This single-center prospective cohort implementation study took place in Ottawa, Canada (from 2011 to 2015). Advanced and primary care paramedics were trained to use the modified Canadian C-spine rule, collect data on a standardized study form, and selectively transport eligible patients without immobilization. We evaluated all consecutive low-risk adult patients (Glasgow Coma Scale [GCS] 15, stable vital signs) at risk for a neck injury. We followed all patients without initial radiologic evaluation for 30 days. Analyses included descriptive statistics with 95% confidence intervals (CI), sensitivity, specificity, and kappa coefficients. The 4,034 enrolled patients had a mean age of 43 (range 16 to 99), and 53.4% were female. Motor vehicle collisions were the most common mechanism of injury (55.1%), followed by falls (23.9%). There were 11 clinically important injuries. The paramedics classified these injuries with a sensitivity of 90.9% (95% CI, 58.7 to 99.8) and specificity of 66.5% (95% CI, 65.1 to 68.0). There was no adverse event or resulting spinal cord injury. The kappa agreement between paramedics and investigators was 0.94. A total of 2,583 (64.0%) immobilizations were avoided using the modified Canadian C-spine rule. Paramedics could accurately apply the modified Canadian C-spine rule to low-risk trauma patients and significantly reduce the need for spinal immobilization during transport. This resulted in no adverse event or any spinal cord injury.


Changes in ocular biomechanics after femtosecond laser creation of a laser in situ keratomileusis flap.
To evaluate ocular biomechanical parameters with the Corvis ST, a noncontact tonometer combined with an ultra-high-speed Scheimpflug camera, before and after creation of a femtosecond laser-created laser in situ keratomileusis (LASIK) flap. Private practice, Siena, Italy. Prospective consecutive study. Right eyes of patients having LASIK were assessed with the dynamic Scheimpflug camera before and after femtosecond laser (LDV Z4) flap creation but before mechanical flap lifting. Twenty-eight eyes of 28 patients were evaluated. Before flap creation, the mean values on the dynamic Scheimpflug camera were intraocular pressure (IOP), 15.04 mm Hg ± 3.99 (SD); central pachymetry, 550.8 ± 101.0 μm; applanation 1 length, 1.721 ± 0.134 mm; applanation 2 length, 1.674 ± 0.287 mm; applanation 1 velocity, 0.126 ± 0.031 m/s; and deflection amplitude, 1.039 ± 0.141 mm. After flap creation, the mean values were IOP, 16.10 ± 3.11 mm Hg (95% confidence interval [CI], 0.44-1.78; P < .05); central pachymetry, 561.8 ± 35.9 μm (95% CI, -28.9 to 50.9; P = .21); applanation 1 length, 1.789 ± 0.1492 mm (95% CI, 0.003-0.134; P < .05); applanation 2 length, 1.759 ± 0.259 mm (95% CI, -0.005 to 0.173; P = .08); applanation 1 velocity, 0.136 ± 0.022 m/s (95% CI, 0.001-0.017; P < .05); and deflection amplitude, 1.029 ± 0.151 mm (95% CI: -0.043 to 0.025; P = .34). The dynamic Scheimpflug camera showed changes in biomechanical properties after femtosecond creation of a LASIK flap as indicated by an increased applanation 1 length and applanation 1 velocity. No author has a financial or proprietary interest in any material or method mentioned.


Macrophage membrane glycoprotein binding of Griffonia simplicifolia I-B4 induces TNF-alpha production and a tumoricidal response.
Thioglycollate-elicited macrophages (m phi), upon binding the lectin Griffonia simplicifolia IB4 (GSIB4) at the plasma membrane, are induced to secrete several low molecular weight proteins. In this investigation, results from specific ELISA and immunoprecipitation analysis of these molecules confirmed that the cytokine, tumor necrosis factor-alpha (TNF-alpha), belongs to the group of elicited proteins. This specific m phi response is directly influenced by the dose of GSIB4 used and the time in contact with the cells. At 40 micrograms/ml GSIB4, the maximum dose of lectin used, the m phi activity was equal to that achieved when the cells were incubated with an interferon-gamma/lipopolysaccharide (IFN/LPS) stimulus alone. Moreover, the data showed that TNF-mediated tumoricidal activity was significantly influenced by GSIB4 binding to the m phi membrane. When the lectin was incubated alone or in sequence with IFN/LPS, this ligand-receptor binding promoted the lysis of WEHI 164 tumor target cells. However, concurrent incubation of both IFN/LPS and GSIB4 with m phi significantly diminished the tumoricidal response. This suggested that one of the metabolic pathways utilized subsequent to receptor-ligand binding was altered by these interactions. When cyclic AMP (cAMP) and inositol triphosphate (IP3) levels were examined, the results showed that the concentration of cAMP was unchanged despite the fact that IP3 levels were significantly enhanced upon m phi-GSIB4 binding. Collectively, the data show that GSIB4 binding to specific glycoproteins in the m phi membrane induces TNF-alpha production and facilitates TNF-alpha dependent tumoricidal responses. It also appears that the transduction of the signal, in part, at least utilizes the phosphatidyl inositol pathway. Finally, it is noteworthy that m phi activity is influenced by the sequence in which GSIB4 is presented to the m phi relative to the IFN/LPS treatment.


Corneal in vivo Confocal Microscopy for Assessment of Non-Neurological Autoimmune Diseases: A Meta-Analysis.
This study aimed to evaluate the features of corneal nerve with in vivo confocal microscopy (IVCM) among patients with non-neurological autoimmune (NNAI) diseases. We systematically searched PubMed, Web of Science, and Cochrane Central Register of Controlled Trials for studies published until May 2021. The weighted mean differences (WMDs) of corneal nerve fiber length (CNFL), corneal nerve fiber density (CNFD), corneal nerve branch density (CNBD), tortuosity, reflectivity, and beadings per 100 μm with a 95% CI between NNAI and control group were analyzed using a random-effects model. The results showed 37 studies involving collective totals of 1,423 patients and 1,059 healthy controls were ultimately included in this meta-analysis. The pooled results manifested significantly decreased CNFL (WMD: -3.94, 95% CI: -4.77--3.12), CNFD (WMD: -6.62, 95% CI: -8.4--4.85), and CNBD (WMD: -9.89, 95% CI: -14--5.79) in NNAI patients. In addition, the NNAI group showed more tortuous corneal nerve (WMD: 1.19, 95% CI:0.57-1.81). The comparison between NNAI patients and healthy controls in beadings per 100 μm corneal nerve length was inconsistent. No significant difference was found in the corneal nerve fiber reflectivity between NNAI and the control group (WMD: -0.21, 95% CI: -0.65-0.24, P = 0.361). The parameters and morphology of corneal nerves observed by IVCM proved to be different in NNAI patients from healthy controls, suggesting that IVCM may be a non-invasive technique for identification and surveillance of NNAI diseases.


Deletions in PITX1 cause a spectrum of lower-limb malformations including mirror-image polydactyly.
PITX1 is a bicoid-related homeodomain transcription factor implicated in vertebrate hindlimb development. Recently, mutations in PITX1 have been associated with autosomal-dominant clubfoot. In addition, one affected individual showed a polydactyly and right-sided tibial hemimelia. We now report on PITX1 deletions in two fetuses with a high-degree polydactyly, that is, mirror-image polydactyly. Analysis of DNA from additional individuals with isolated lower-limb malformations and higher-degree polydactyly identified a third individual with long-bone deficiency and preaxial polydactyly harboring a heterozygous 35 bp deletion in PITX1. The findings demonstrate that mutations in PITX1 can cause a broad spectrum of isolated lower-limb malformations including clubfoot, deficiency of long bones, and mirror-image polydactyly.


The Contribution of National Spontaneous Reporting Systems to Detect Signals of Torsadogenicity: Issues Emerging from the ARITMO Project.
Spontaneous reporting systems (SRSs) are pivotal for signal detection, especially for rare events with a high drug-attributable component, such as torsade de pointes (TdP). Use of different national SRSs is rarely attempted because of inherent difficulties, but should be considered on the assumption that rare events are diluted in international databases. The aim was to describe TdP-related events associated with antipsychotics, H1-antihistamines and anti-infectives in three national SRSs (in Italy, Germany and France) and highlight potential signals of torsadogenicity through a combined literature evaluation. A common search strategy was applied to extract TdP-related events: (1) TdP, (2) QT interval abnormalities, (3) ventricular fibrillation/tachycardia, and (4) sudden cardiac death. Signals of disproportionate reporting (SDRs) were calculated for TdP + QT interval abnormalities and defined by a lower limit of the 95 % confidence interval of the reporting odds ratio (ROR) >1. Among SDRs with at least three cases without concomitant pro-arrhythmic drugs, we defined potential new signal of torsadogenicity as drugs with no published evidence from (a) the crediblemeds(®) website ( http://www.crediblemeds.com , as of November 1st, 2014); (b) studies on the FDA Adverse Event Reporting System (FAERS); and (c) safety trials or pharmaco-epidemiological studies (as of December 16th, 2014). Overall, 3505 cases were retrieved (1372, 1468, and 801 for France, Germany and Italy, respectively). Antipsychotics were mainly recorded in Germany (792 cases), whereas antibiotics peaked at 515 and 491 (France and Italy, respectively). Forty-one drugs met criteria for SDRs in at least one single source, of which 31 were detected only from one single SRS: 18, ten and three (French, German and Italian SRS, respectively). By contrast, only five SDRs were detected in all national data sources (amisulpride, aripiprazole, haloperidol, olanzapine, risperidone). Overall, five potential new signals of torsadogenicity were identified: flupentixol, ganciclovir, levocetirizine, oxatomide and tiapride. We found differences across and within national SRSs in the reporting of drug-induced TdP, which finally resulted in five potential new signals of torsadogenicity. These findings warrant targeted pharmacovigilance studies to formally assess the existence of actual drug-event associations.


Hepatitis C and the Impact of Host Genetics.
This commentary highlights the article by Enache et al that describes a diagnostic test for simultaneous genotyping of specific single nucleotide polymorphisms in chronic hepatitis C patients.


Transperineal sector prostate biopsies: a local anesthetic outpatient technique.
To describe our technique and determine the feasibility and tolerability of transperineal template prostate (TP) biopsies under local anesthesia (LA). Fifty consecutive patients underwent TP biopsies under LA for investigation of an elevated prostate-specific antigen level or risk stratification as part of our active surveillance protocol. Tolerability was evaluated with a visual analog scale assessing probe discomfort, LA infiltration, and the biopsy procurement. Patients were also asked if they would have the procedure again, and in those who had undergone previous transrectal biopsies, how the TP technique compared. Pathologic data, clinical outcomes, and complications were recorded at 2 weeks. Mean age was 62.8 years (standard deviation [SD], 6.34 years) and the mean prostate-specific antigen level was 8.49 ng/mL (SD, 6.36 ng/mL). Mean prostate volume was 48.2 mL (SD, 19.4 mL). Mean visual analog scale scores for discomfort caused by the ultrasound probe, LA injections, and biopsies were 3.08 (SD, 1.64), 3.29 (SD, 1.13), and 2.88 (SD, 1.28), respectively. Thirty-four of 50 men (68%) had positive histology, 26 men had Gleason score≤3+4, 5 men had Gleason score≥4+3, and 3 had recurrent adenocarcinoma after radiotherapy. There were 2 complications: 1 Clavien score 1 and 1 Clavien score 3a. LA TP biopsies are well tolerated, acceptable, and feasible when carried out within an outpatient setting.


Prevention of experimental allergic neuritis in the Lewis rat with bovine P2 protein.
Protective doses of bovine P2 protein (5, 15 or 50 micrograms) in incomplete Freund's adjuvant (IFA) were administered to Lewis rats and were followed 2, 4 or 10 weeks later by challenging doses of either 250 micrograms bovine P2 or 2.5 mg bovine PNS myelin in complete Freund's adjuvant (CFA). Protection from experimental allergic neuritis (EAN) could be achieved with a single dose of 5 micrograms of P2 in IFA. There was little difference between prophylactic 5 micrograms and 15 micrograms doses of P2. The degree of protection depended upon the interval between protective innoculation and challenge. Protection was partial at 2 weeks and maximal at 4 weeks at which time there was complete protection against P2-induced EAN and less complete protection from myelin-induced disease. Complete protection at 4 weeks from myelin-induced EAN was achieved with a 50 micrograms dose. Protection lasted for at least 10 weeks (the longest interval assessed) and was complete with respect to P2-induced EAN. Partial protection was observed in myelin-challenged animals after 10 weeks with the level of protection greater than that observed after 2 weeks.


Comparison of the electrophysiological effects of two neuroleptics, melperone and thioridazine, on isolated rat atria.
The effects of the two neuroleptics, melperone (a butyrophenone) and thioridazine (a phenothiazine), were compared on the electrical and mechanical activity of isolated rat atria. Both electrically stimulated and spontaneously beating atria were used. Melperone was found to prolong the effective refractory period while the threshold for electrical stimulation i.e. the excitability, was almost unaffected. Thioridazine caused a similar prolongation of the effective refractory period, but also decreased the excitability significantly. In contrast to melperone, thioridazine had a negative inotropic effect. The spontaneous pacemaker activity was depressed and the sinus node recovery time increased to a greater extent after melperone than after thioridazine. The results taken together with other recent data support the hypothesis that melperone may be a type III anti-arrhythmic according to the classification of Vaughan Williams, in contrast to thioridazine which has a quinidine-like action (type I). The results also indicate that melperone in addition to prolonging the effective refractory period, may act as an anti-arrhythmic agent by depressing automaticity.


A histochemical study on the innervation of the pancreas of the one-humped camel (Camelus dromedarius).
Autonomic innervation of the pancreas of the camel has been studied using histochemical techniques for the demonstration of adrenergic and cholinergic (acetylcholinesterase-positive) nerves. Both extrinsic and intrinsic innervation of the pancreas were found. Distinct peri-acinar, perivascular, peri-insular and periductal plexuses were found as well as both adrenergic and cholinergic ganglia. The role of the autonomic nerves in the synthesis and release of insulin, glucagon and somatostatin is discussed.


[Prediction of end of lockdown post-peak of cases in first wave of the COVID-19 pandemic in Chile].
The results of mandatory confinement have been detrimental in several respects. Nonetheless, they have resulted in reducing the number of active cases of COVID-19. Chile has begun the de-escalation and needs to know the best time to end the restrictions. We discuss the best conditions and guarantees for the end of compulsory confinement. This study is based on a trend model with prediction estimation. The data of the variables of interest were subjected to linear regression studies to determine the curve that best explained the data. The coefficient of determination, the standard deviation of y in x, and the confidence interval of the observed curve were estimated. The trend curve was chosen in accordance with the regression estimates. It was found that all dependent variables tended to decrease over time in a quadratic fashion, except for the new cases variable. In general, the R2 and MAPE estimates are satisfactory, except for the variable number of PCR tests per day. Gradual and cautious steps should be taken before ending mandatory confinement. In the current de-escalator, daily PCR tests should be increased, maintaining vigilance on indicators of incidence, prevalence, and positivity of PCR tests. Evidence suggests with some degree of confidence that mandatory confinement could be safely lifted as of August 30, 2020. Long-term preparations must be made to contain future waves of new cases.


IMPPACT: Investigation of Medical Professionals and Patients Achieving Control Together.
To determine whether home blood pressure monitoring (HBPM) led to physician-initiated medication titration and improved achievement of target BP levels compared with standard, office-based management. Physicians were randomly assigned to a treatment group or a control group. Patients in the control group were monitored by their physician and were drug-adjusted according to the usual approach. In the treatment group, patients were given home BP monitors (UA-767P [A&D Medical/Lifesource, USA]), and drug dosing was adjusted according to HBPM readings and protocol. Long-acting diltiazem (240 mg/day) was added at baseline, which was adjusted as necessary (other medications were added if more than 360 mg/day of diltiazem was required). A final BP measurement was taken in the office after six weeks. Nineteen physicians were randomly assigned to the office BP monitoring group and 34 were assigned to the HBPM group. Of the 270 subjects recruited, 97 were in the office BP monitoring group and 173 were in the HBPM group. From baseline to the final visit, there was a statistically significant time by group interaction with lower BP in the HBPM group (P=0.034 for both systolic BP and diastolic BP). BP fell from 159/91+/-11/10 mmHg at baseline in the HBPM group to 138/80+/-13/8 mmHg on the final visit, and from 160/88+/-14/10 mmHg to 141/78+/-10/9 mmHg in the control group. BP was lowered significantly in both groups, and to a statistically greater degree in the HBPM group. The Hawthorne effect might have led to altered care by the physicians with improvement in BP control in both groups.


Case of sisters with complete androgen insensitivity syndrome and discordant Müllerian remnants.
Presentation of complete androgen insensitivity in two members of the same family with differing residual Müllerian tissue. Case report. Rural hospital setting. Two siblings with 46,XY karyotype and female phenotype presented at different points in time with primary amenorrhea. Laparoscopy of sister 1 revealed bilateral elongated gonads and remnants of uterine tissue. Laparoscopy of sister 2 demonstrated both gonads, but no uterus was identified. Sister 1: bilateral gonadectomy and hysterectomy. Sister 2: bilateral gonadectomy. Gonadectomy for cancer prophylaxis, counseling in affected/unaffected family members. Sister 1: pathology revealed portions of immature testicles and fragments of smooth muscle. Sister 2: pathology reported two testicular and epididymal-like structures with benign Sertoli cell adenomas entirely in testicular parenchyma. This case demonstrates the presentation and laparoscopic photos of complete androgen insensitivity syndrome discovered in two siblings. Both girls are genotypically male, but differ in the presence of vestigial Müllerian tissue. This case demonstrates that siblings with androgen resistance may express varying amounts of Müllerian tissue.


Skeletal muscle oxygen uptake in obese patients: functional evaluation by knee-extension exercise.
We hypothesized, in a group of obese women (OB), a more significant impairment of aerobic metabolism during knee extension (KE) exercise vs. that described during cycle ergometer exercise, lending support to the role of skeletal muscles in limiting exercise tolerance in OB. Eleven OB (age 29.5 ± 5.5 years, body mass index 43.2 ± 5.4 kg m(-2)) and 10 non-obese controls (CTRL) women were tested. Fat-free mass of a lower-limb (FFMLL) was assessed by a densitometer. Heart rate (HR) and pulmonary O2 uptake (VO2) were determined during incremental exercise tests to voluntary exhaustion carried out on a custom-built KE ergometer and on a cycle ergometer (CE). FFMLL and maximal isometric force of KE muscles were higher in OB vs. CTRL (+42.4 and +46.2 %, respectively). Peak work rate was significantly lower in OB (-18.4 %) vs. CTRL in CE, but not in KE. Expressed in mL min(-1), peak VO2 was not different in OB vs. CTRL in CE and in KE. After it was divided per unit of FFM involved in the exercises, peak VO2 was significantly lower in OB vs. CTRL, both for CE (-19 %) and KE (-33 %). Expressed per unit of exercising muscle mass, peak oxidative function is impaired in OB. The impairment is more pronounced after limitations related to cardiovascular O2 delivery are reduced. In OB muscle hypertrophy and the increased muscle force allow to preserve exercise tolerance during aerobic exercises carried out by relatively small muscle masses.


Malignant neuroleptic syndrome--its present status in Japan and clinical problems.
Fourteen cases in which hyperpyrexia, akinesia, mutism, extrapyramidal symptoms and severe, diverse autonomic symptoms developed in the course of neuroleptic drug therapy are reported as the malignant neuroleptic syndrome, with analysis and discussion of the clinical features and pathogenic factors. Possible factors contributing to the danger of evoking this syndrome are: 1. Physical exhaustion associated with dehydration, and 2. Parenteral administration of neuroleptic agents, especially of the incisive type. Symptomatologic similarity of the syndrome to the condition known as malignant hyperthermia during anesthesia is also discussed.


Author Correction: Immunofluorescence can assess the efficacy of mTOR pathway therapeutic agent Everolimus in breast cancer models.
An amendment to this paper has been published and can be accessed via a link at the top of the paper.


Alternative mechanisms for the potentiation of the relaxation evoked by isoprenaline in aortae from young and aged rats.
The action of cinnarizine and flunarizine on the relaxant effect of isoprenaline was studied in the isolated rat aorta and was compared with the action of papaverine. The results show that isoprenaline-induced relaxation and K+ contraction were reduced. On the contrary, in the presence of papaverine, isoprenaline relaxation and K+ contraction were reduced. On the contrary, in the presence of papaverine, isoprenaline relaxation was enhanced by cinnarizine and flunarizine at concentrations which were lower that those required for inducing an inhibition of the contraction evoked by K+ in the presence of 1.25 mM CaCl2; with concentrations higher than 10(-8) M both isoprenaline relaxation was enhanced and K+ contraction was depressed in a dose-dependent manner. In aged rats, isoprenaline-induced relaxation was tachyphylactic. The tachyphylaxis was prevented by cinnarizine and flunarizine. The present observations indicate that several processes might be responsible for potentiating isoprenaline action.


Sampling port for real-time analysis of bioaerosol in whole body exposure system for animal aerosol model development.
Multiple factors influence the viability of aerosolized bacteria. The delivery of aerosols is affected by chamber conditions (humidity, temperature, and pressure) and bioaerosol characteristics (particle number, particle size distribution, and viable aerosol concentration). Measurement of viable aerosol concentration and particle size is essential to optimize viability and lung delivery. The Madison chamber is widely used to expose small animals to infectious aerosols. A multiplex sampling port was added to the Madison chamber to measure the chamber conditions and bioaerosol characteristics. Aerosols of three pathogens (Bacillus anthracis, Yersinia pestis, and Mycobacterium tuberculosis) were generated under constant conditions and their bioaerosol characteristics were analyzed. Airborne microbes were captured using an impinger or BioSampler. The particle size distribution of airborne microbes was determined using an aerodynamic particle sizer (APS). Viable aerosol concentration, spray factor (viable aerosol concentration/inoculum concentration), and dose presented to the mouse were calculated. Dose retention efficiency and viable aerosol retention rate were calculated from the sampler titers to determine the efficiency of microbe retention in lungs of mice. B. anthracis, Y. pestis, and M. tuberculosis aerosols were sampled through the port. The count mean aerodynamic sizes were 0.98, 0.77, and 0.78 μm with geometric standard deviations of 1.60, 1.90, and 2.37, and viable aerosol concentrations in the chamber were 211, 57, and 1 colony-forming unit (CFU)/mL, respectively. Based on the aerosol concentrations, the doses presented to mice for the three pathogens were 2.5e5, 2.2e4 and 464 CFU. Using the multiplex sampling port we determined whether the animals were challenged with an optimum bioaerosol based on dose presented and respirable particle size.


Improving identification of molecularly imprinted monolith to benzoylation modified peptides by a deep eutectic solvents monomer-induced cooperation.
In this study, a strategy of improving imprinting performance was developed using an enhanced cooperation effect of functional monomers based on deep eutectic solvents (DESs) monomer for the specific enrichment of benzoylation modified peptides. Zinc acrylate and DESs monomers were used as binary functional monomers, and ethylene glycol dimethacrylate was used as the cross-linking agent with SGRGKbz as template to prepare an imprinted monolith. It was observed that the use of DESs monomer significantly improveed the affinity of benzoylation imprinted monolith and increased the adsorption capacity. Under optimal conditions, the recovery and imprinting factor (IF) of the imprinted monolith for SGRGKbz can reach 93.0% and 10.58, respectively. The average recovery of SGRGKbz extracted from the spiked histone digestion solution can reach 88.4% (n = 5, RSD = 3.4%). After treatment with the benzoylation imprinted monolith, 12 benzoylation modified peptides, 13 benzoylation modified sites and 12 benzoylation proteins could be identified in the digestion of mouse liver protein, while only one of each benzoylation modified peptide, benzoylation modified site and benzoylation protein could be identified in the untreated digestion of mouse liver protein. The results indicated that the prepared imprinted monolith using DESs-based functional monomer was an effective method to increase the affinity of the resulting MIP.


Manual discrimination capability when only viscosity is varied in viscoelastic stiffness stimuli.
Training manual therapists in the judgment of spinal stiffness traditionally requires the spines of human volunteers. Presenting the range of stiffness values representative of spines requires both time and resources. When investigating the ability of therapists to judge spinal stiffness, several studies have therefore utilized spine analogues, nonbiological devices designed to present either purely elastic stimuli or viscoelastic stimuli with unknown relative contributions of elastic and viscous components. Previous research has suggested that the viscous component of stiffness is more difficult to judge. This study determined for each subject the just-noticeable difference, or discrimination threshold, for manual judgment of viscous stiffness against a constant elastic and friction background. This psychophysical study utilized the Weber fraction as a measure of the ability of subjects to discriminate between viscoelastic stiffness stimuli. Twenty-five subjects with both physiotherapy and lay backgrounds volunteered to participate in the study. Stiffness stimuli were generated by a device incorporating a fluid-filled plunger and a spring, with only the amount of viscous stiffness being manipulated by the experimenter. The method of constant stimuli was used to estimate the just-discriminable change in viscous stiffness, and results were expressed as a percentage of the base stiffness or Weber fraction. The mean Weber fraction for manual judgments of viscous stiffness was 14.7%. For 13 of the subjects who had previously participated in elastic stiffness discrimination studies, the Weber fraction for viscous stimuli was significantly greater than that for elastic stimuli. The significantly higher Weber fraction for viscous stiffness perception compared with that for pure elastic stiffness suggests that the poor reliability of manual judgments of spinal stiffness may be due to the difficulty in judging the viscous stiffness component.


Marsupial BRCA1: conserved regions in mammals and the potential effect of missense changes.
More than half of the reported missense changes in the breast cancer susceptibility protein BRCA1 occur in exon 11, but none has been clearly identified as disease associated and only 28 are designated 'probable' neutral polymorphisms. Previously, in a comparison of sequences from 57 eutherian mammal species, we found seven 'highly conserved regions' between amino acids 282 and 1103, and identified 38 missense changes as likely to disrupt gene function. These conserved regions were also present in birds and amphibians and included only six of the mutations predicted to affect function. In this new analysis, we hypothesized that using 37 ancestral sequences derived from the 57 GenBank sequences and including eight marsupial sequences would allow us to identify regions unique to mammals and refine our predictions of disease-associated missense changes. We identified 13 conserved regions, three of which appear to be unique to mammals, and 21 likely disease-associated missense changes, 11 of which occur in conserved regions. Seven regions identified in this analysis, including the three found only in mammalian sequences, and nine missense changes predicted to affect function are in the putative STAT1-interaction domain, suggesting that the role of STAT1 in immune response is important to mammary function. The reduction in the number of missense changes predicted to be disease associated and the identification of conserved regions specific to mammals can facilitate the further study of the role of missense changes in BRCA1-associated breast cancers.


Wen-Shen-Jian-Pi-Hua-Tan decoction protects against early obesity-related glomerulopathy by improving renal bile acid composition and suppressing lipogenesis, inflammation, and fibrosis.
Obesity is an independent predictor of chronic kidney disease (CKD) development and may directly lead to kidney lesions such as obesity-related glomerulopathy (ORG) which might play a vital pathogenic role in obese patients with CKD. Wen-Shen-Jian-Pi-Hua-Tan decoction (WSHT) has been clinically used for the treatment of obesity and obesity-related metabolic diseases for years. However, the renoprotective effects and potential mechanism of action of WSHT against ORG remain unknown. This study aimed to explore the potential effect of WSHT on ORG and reveal its mechanisms in high-fat diet (HFD)-induced obese rats. An animal model of early stage ORG was established using HFD-induced obese rats. After treatment with WSHT for 6 weeks, an integrated metabolomics and molecular biology strategy was utilized to illustrate the effects and mechanism of WSHT on ORG. First, UPLC-ESI-MS/MS-based targeted metabolomics was used to analyze renal bile acid (BA) levels. Biochemical, histological, and immunofluorescence assays; electron microscopy; and western blotting were performed to evaluate the efficacy of WSHT against ORG and its underlying mechanisms in vivo. Our results showed that an HFD led to hyperlipidemia, proteinuria, renal lipid deposition, effacement of podocyte foot processes, and increased expression of proinflammatory factors and profibrotic growth factors in ORG rats. In addition, an HFD decreased the levels of renal BAs such as cholic acid, chenodeoxycholic acid, and lithocholic acid. After 6 weeks of treatment, WSHT markedly attenuated dyslipidemia and reduced body, kidney and epididymal fat weights in ORG rats. WSHT also significantly increased BA levels, suggesting that it altered BA composition; the effects of BAs are closely associated with farnesoid X receptor (FXR) activation. WSHT alleviated fat accumulation, podocyte loss and proteinuria, and reduced the expression of proinflammatory cytokines and profibrotic growth factors in the kidneys of ORG rats. Finally, WSHT remarkably upregulated the renal expression of FXR and salt-induced kinase 1 and blocked the renal expression of sterol regulatory element-binding protein-1c and its target genes. WSHT attenuated early renal lesions in ORG rats by improving renal BA composition and suppressing lipogenesis, inflammation and fibrosis. This study develops a new way to alleviate obesity-induced renal damages.


Delay of cancer anorexia following intraventricular injection of para-chlorophenylalanine.
Serotonergic mediation of cancer anorexia was investigated in immature female rats following the intraventricular injection of para-chlorophenylalanine (PCPA) or normal saline. Significant anorexia developed 6 days after the induction (IM) of Walker 256 carcinosarcomas in saline-treated rats. Although tumor-bearing rats treated with PCPA ate less than PCPA-injected controls by day 7, their feeding response was significantly greater than that of saline-treated tumor-bearing rats on days 5, 6 and 7. The PCPA treatment had no significant effect on food intake in nontumor-bearing rats. Biochemical analysis revealed significant elevations in plasma free tryptophan, brain tryptophan and brain 5-hydroxyindoleacetic acid in saline-treated tumor-bearing rats. Brain serotonin, 5-hydroxyindoleacetic acid and norepinephrine levels were decreased in PCPA-treated rats. Although these data may provide some support for a serotonergic mediation of cancer anorexia, additional mechanisms are clearly indicated.


Mouse prepro-epidermal growth factor synthesis by the kidney and other tissues.
Epidermal growth factor (EGF), a protein comprising 53 amino acids, is derived from a precursor of 1,217 amino acids that includes at least seven EGF-like sequences. EGF has diverse biological activities: it is a potent mitogen for many tissue culture cells, inhibits gastric acid secretion from the intestinal mucosa and promotes healing of the corneal epithelium. EGF given to fetal animals accelerates several developmental processes including palate formation, incisor eruption, eyelid opening and lung maturation. However, the physiological roles of EGF in vivo are unknown. The presence of high-affinity receptors in many fetal and adult tissues suggests that EGF is involved in normal cellular functions. Immunocytochemical studies have revealed the presence of EGF in mouse and human submaxillary glands, rat brain and human intestine. The low levels of EGF in extracts from many tissues may reflect sequestration rather than synthesis of the polypeptide. We show here that several mouse tissues contain preproEGF mRNA and that it is synthesized mainly in the distal tubules of the kidney. PreproEGF does not seem to be processed to EGF or other peptides in this tissue.


Intraductal carcinoma of the prostate can evade androgen deprivation, with emergence of castrate-tolerant cells.
To determine the relevance of intraductal carcinoma of the prostate (IDC-P) in advanced prostate cancer by first examining whether IDC-P was originally present in patients who later developed advanced prostate cancer and then using patient-derived xenografts (PDXs) to investigate the response of IDC-P to androgen deprivation therapy (ADT). We conducted a retrospective pathology review of IDC-P in primary prostate biopsy or surgery specimens from 38 men who subsequently developed advanced prostate cancer. Overall survival was calculated using the Kaplan-Meier method. To demonstrate the response of IDC-P to ADT, we established PDXs from seven patients with familial and/or high-risk sporadic prostate cancer. After castration and testosterone restoration of host mice, we measured the volume and proliferation of IDC-P within PDX grafts. We found that IDC-P was a prominent feature in the primary prostate specimens, present in 63% of specimens and often co-existing with poorly differentiated adenocarcinoma. Overall survival was similar in patients with or without IDC-P. In the PDXs from all seven patients, IDC-P was identified and present at a similar volume to adenocarcinoma. Residual IDC-P lesions persisted after host castration and, similar to castrate-tolerant adenocarcinoma, testosterone restoration led to tumour regeneration. The study showed that IDC-P is prevalent in aggressive prostate cancer and contains cells that can withstand androgen deprivation. Thus, IDC-P appears functionally relevant in advanced prostate cancer. The presence of IDC-P may be a trigger to develop innovative clinical management plans.


Meal skipping linked to increased visceral adipose tissue and triglycerides in overweight minority youth.
To investigate the impact of eating frequency on dietary intake, physical activity (PA), metabolic, and adiposity measures in minority youth. This analysis included 185 overweight (≥85th BMI percentile) Hispanic and African-American youth (8-18 years) with the following cross-sectional measures: height, weight, BMI, dietary intake, body composition, metabolic parameters, PA, visceral adipose tissue (VAT), and subcutaneous adipose tissue. Each eating occasion (EO) was defined as ≥50 calories and ≥15 minutes from any previous EO. Participants were dichotomized based on EOs per 24-h into meal skippers <3 EO (MS; n = 27) or normal/frequent eaters ≥3 EO (NFE; n = 158). ANCOVAs were used to assess dietary intakes, metabolic outcomes, adiposity, and PA between eating frequency groups. MS compared to NFE consumed 24% fewer calories per 24-h (P ≤ 0.01), 21% more calories per EO (P ≤ 0.01), ate 40% less often (P ≤ 0.01), had 18% higher triglycerides (P = 0.03), and 26% more VAT (P = 0.03), with no differences in PA. Although meal skipping was associated with decreased energy intake, it was linked to increased calories per EO and higher triglycerides and VAT, which are strong indicators of deleterious metabolic profiles. These findings elucidate that meal skipping may be associated with increased VAT and related metabolic diseases in high-risk minority youth.


Electrical tuning of elastic wave propagation in nanomechanical lattices at MHz frequencies.
Nanoelectromechanical systems (NEMS) that operate in the megahertz (MHz) regime allow energy transducibility between different physical domains. For example, they convert optical or electrical signals into mechanical motions and vice versa1. This coupling of different physical quantities leads to frequency-tunable NEMS resonators via electromechanical non-linearities2-4. NEMS platforms with single- or low-degrees of freedom have been employed to demonstrate quantum-like effects, such as mode cooling5, mechanically induced transparency5, Rabi oscillation6,7, two-mode squeezing8 and phonon lasing9. Periodic arrays of NEMS resonators with architected unit cells enable fundamental studies of lattice-based solid-state phenomena, such as bandgaps10,11, energy transport10-12, non-linear dynamics and localization13,14, and topological properties15, directly transferrable to on-chip devices. Here we describe one-dimensional, non-linear, nanoelectromechanical lattices (NEML) with active control of the frequency band dispersion in the radio-frequency domain (10-30 MHz). The design of our systems is inspired by NEMS-based phonon waveguides10,11 and includes the voltage-induced frequency tuning of the individual resonators2-4. Our NEMLs consist of a periodic arrangement of mechanically coupled, free-standing nanomembranes with circular clamped boundaries. This design forms a flexural phononic crystal with a well-defined bandgap, 1.8 MHz wide. The application of a d.c. gate voltage creates voltage-dependent on-site potentials, which can significantly shift the frequency bands of the device. Additionally, a dynamic modulation of the voltage triggers non-linear effects, which induce the formation of a phononic bandgap in the acoustic branch, analogous to Peierls transition in condensed matter16. The gating approach employed here makes the devices more compact than recently proposed systems, whose tunability mostly relies on materials' compliance17,18 and mechanical non-linearities19-22.


Surface bundles over surfaces: new inequalities between signature, simplicial volume and Euler characteristic.
We present three new inequalities tying the signature, the simplicial volume and the Euler characteristic of surface bundles over surfaces. Two of them are true for any surface bundle, while the third holds on a specific family of surface bundles, namely the ones that arise through ramified coverings. These are among the main known examples of bundles with non-zero signature.


High glucose promotes hepatic fibrosis via miR‑32/MTA3‑mediated epithelial‑to‑mesenchymal transition.
Hepatic fibrosis is characterized by the aberrant production and deposition of extracellular matrix (ECM) proteins. Growing evidence indicates that the epithelial‑mesenchymal transition serves a crucial role in the progression of liver fibrogenesis. Although a subset of microRNAs (miRNAs or miRs) has recently been identified as essential regulators of the EMT gene expression, studies of the EMT in hyperglycemic‑induced liver fibrosis are limited. In the current study, it was observed that high glucose‑treated AML12 cells occurred EMT process, and miR‑32 expression was markedly increased in the liver tissue of streptozotocin‑induced diabetic rats and in high glucose‑treated AML12 cells. Additionally, the contribution of the EMT to liver fibrosis by targeting metastasis‑associated gene 3 (MTA3) under hyperglycemic conditions was suppressed by AMO‑32. The results indicated that miR‑32 and MTA3 may be considered as novel drug targets in the prevention and treatment of liver fibrosis under hyperglycemic conditions. These finding improves the understanding of the progression of liver fibrogenesis.


Network analysis of Weyl semimetal photogalvanic systems.
We develop a general methodology capable of analyzing the response of Weyl semimetal (WSM) photogalvanic networks. Both single-port and multiport configurations are investigated via extended versions of Norton's theorem. An equivalent circuit model is provided where the photogalvanic currents induced in these gapless topological materials can be treated as polarization-dependent sources. To illustrate our approach, we carry out transport simulations in arbitrarily shaped configurations involving pertinent WSMs. Our analysis indicates that the photogalvanic currents collected in a multi-electrode system directly depend on the geometry of the structure as well as on the excitation and polarization pattern of the incident light. Our results could be helpful in designing novel optoelectronic systems that make use of the intriguing features associated with WSMs.


Critical incident exposure among custody and noncustody correctional workers: Prevalence and impact of violent exposure to work-related trauma.
Correctional workers are at high risk for exposure to trauma, both as direct violence and as threats to their safety and well-being. The distress associated with these critical incidents (CIs) affects mental and physical health. Current tools are limited for detecting CIs in this workforce and are therefore insufficient for addressing correctional worker trauma. Community prison employees (N = 105) self-reported CIs using the adapted Correctional Worker Critical Incident Survey (CWCIS). We examined: (1) prevalence of CIs and occurrences, (2) differences in exposures to CIs by custody and noncustody staff, and (3) differences in job satisfaction, posttraumatic stress (PTSD), lower back disease, and health behaviors, such as missed work and sleep. CIs occurred among most staff (59%) and more often for custody staff as compared to noncustody staff. CIs most often experienced were coworker injury, exposure to disease, and badly beaten adults (frequency 10-50). For the 1-9 frequency category, the most described events were: seeing someone dying, life threatened, and coworker injury. PTSD was identified in 44% of staff, and those who experienced CIs reported lower job satisfaction, greater feelings of PTSD, and more work absences than those not experiencing CIs (p < 0.05). CIs and PTSD are prevalent among custody and noncustody correctional workers; and job dissatisfaction, PTSD, and work absence are significantly worse for those who experienced CIs. The CWCIS detected CIs; future study is needed to inform trauma prevention, reduction, and rehabilitation interventions specific to correctional work.


Effects of verapamil and diltiazem on the ventricular rate during simulated atrial flutter in isolated guinea pig hearts.
To compare the direct effects of verapamil and diltiazem on the ventricular rate during atrial flutter, we developed an atrial flutter model in guinea pig isolated hearts. Atrial flutter was simulated by rapid atrial pacing (cycle length = 50 ms). At this atrial pacing cycle length, the shape of the frequency of distribution of the ventricular cycle lengths was comparable to that during spontaneous atrial flutter. Verapamil (0.01, 0.03 microM) and diltiazem (0.03, 0.09 microM) caused a comparable prolongation of the atrioventricular conduction time and atrioventricular refractoriness. Also, the anterograde Wenckebach cycle length was increased to a comparable degree by both substances. The mean ventricular cycle length during atrial flutter was comparable prolonged by both substances. The prolongation of the maximal ventricular cycle length was significantly more pronounced in the presence of verapamil. The time dependence of drug-induced alterations in atrioventricular conduction time during abrupt changes of heart rate is significantly more pronounced in the presence of verapamil compared to diltiazem. In conclusion, the more pronounced effect of verapamil on the maximal ventricular cycle length compared to the action of diltiazem may be explained by the slow binding kinetic of this drug to the Ca2+ channel resulting in a longlasting blockade of the Ca2+ channel.


Work-related Internet use as a threat to work-life balance - a comparison between the emerging on-line professions and traditional office work.
In the present study, the authors focused on the comparison of work characteristics related to the possibility of striking the right work- nonwork balance, as well as satisfaction with the actual work-life balance (WLB), negative work-to-home conflict and the quality of life related to social relationships, between a new group of on-line workers (social media or e-marketing specialists, search engine optimization or search engine marketing specialists, e-public relations experts etc.) and traditional office workers. The authors conducted a questionnaire study covering 189 on-line workers (whose work required permanent presence on-line) and 200 office workers (using the Internet mainly to communicate with other departments and to search for information). The results showed that the on-line workers reported a significantly lower satisfaction with WLB and a higher negative work-home interaction. The authors found no differences as regards the social quality of life between the studied groups. These findings confirm that technology advancement opens a new chapter in organizational psychology and occupational health, especially in the context of the emerging on-line occupations. Int J Occup Med Environ Health. 2020;33(1):21-33.


[Problems of occupational rehabilitation in the shipbuilding industry. II. Rehabilitation in a group of ship welders].
The causes of rehabilitation of welders employed in the Maritime Shipyard in Szczecin have been analysed for the period 1979-1984. The main causes were found to be diseases of the musculo-osseous system (18.9%) and respiratory tract (14.8%). Temporary rehabilitation covered 67.3% of welders (2/3 for respiratory tract diseases), whereas permanent rehabilitation--23.5% (2/3 for musculo-osseous diseases).


The social construction of nurse educator professional identities: Exploring the impact of a community of practice through participatory action research.
The aim of the study was to explore whether, and how, professional nurse educator identity is co-constructed by a community of practice. A critical participatory action research (PAR) methodology was used as it extends the principles of action research by seeking purposeful and sustainable social change that recognizes participants as researchers and generators of knowledge. Twenty-two sector-based nurse educators employed as either nurse educators or clinical nurse educators participated in the critical PAR. Multiple methods of data generation were pursued in a cyclic and sequential manner consistent in an action research process. Three distinct phases of the research across 2015-2017 involved the generation of data before, during and after the establishment of a nurse educator community of practice. A social constructionist lens of analysis was used to explore the social and relational outcomes. The COREQ checklist was used to appraise the study report. A sustained period of community of practice engagement enhanced the participants' relationships and shifted their perceived professional identities towards being validated nurse educators with a stronger collective sense of their roles. For this group of nurse educators, participation in the research resulted in collective meaning-making, praxis, knowledge generation and the co-construction of their professional identities.


Deciphering the code: Identifying true gamma neural oscillations.
Neural oscillatory activity occurring in the gamma frequency range (30-80 Hz) has been proposed to play essential roles in sensory and cognitive processing. Supporting this, abnormalities in gamma oscillations have been reported in patients with diverse neurological and neuropsychiatric disorders in which cognitive impairment is prominent. Understanding the mechanisms underpinning this relationship is the focus of extensive research. But while an increasing number of studies are investigating the intricate relationship between gamma oscillations and cognition, interpretation and generalisation of these studies is limited by the diverse, and at times questionable, methodologies used to analyse oscillatory activity. For example, a variety of different types of gamma oscillatory activity have been characterised, but all are generalised non-specifically as 'gamma oscillations'. This creates confusion, since distinct cellular and network mechanisms are likely responsible for generating these different types of rhythm. Moreover, in some instances, certain analytical measures of electrophysiological data are overinterpreted, with researchers pushing the boundaries of what would be considered rhythmic or oscillatory in nature. Here, we provide clarity on these issues, firstly presenting an overview of the different measures of gamma oscillatory activity, and describing common signal processing techniques used for analysis. Limitations of these techniques are discussed, and recommendations made on how future studies should optimise analyses, presentation and interpretation of gamma frequency oscillations. This is an essential progression in order to harmonise future studies, allowing us to gain a clearer understanding of the role of gamma oscillations in cognition, and in cognitive disorders.


Application of a solid-phase beta-triphosphitylating reagent in the synthesis of nucleoside beta-triphosphates.
A beta-triphosphitylating reagent was subjected to reaction with aminomethyl polystyrene resin-bound p-acetoxybenzyl alcohol to yield the corresponding polymer-bound beta-triphosphitylating reagent. The solid-phase reagent was reacted with unprotected nucleosides (e.g., 3'-azido-3'-deoxythymidine, cytidine, thymidine, uridine, inosine, or adenosine) in the presence of 1H-tetrazole. Polymer-bound nucleosides underwent oxidation with t-butyl hydroperoxide, deprotection of cyanoethoxy groups with DBU, and the acidic cleavage, respectively, to afford only monosubstituted 5'-O-beta-triphosphorylated nucleosides.


Multigene phylogenies of diverse Carpediemonas-like organisms identify the closest relatives of 'amitochondriate' diplomonads and retortamonads.
Diplomonads, retortamonads, and "Carpediemonas-like" organisms (CLOs) are a monophyletic group of protists that are microaerophilic/anaerobic and lack typical mitochondria. Most diplomonads and retortamonads are parasites, and the pathogen Giardia intestinalis is known to possess reduced mitochondrion-related organelles (mitosomes) that do not synthesize ATP. By contrast, free-living CLOs have larger organelles that superficially resemble some hydrogenosomes, organelles that in other protists are known to synthesize ATP anaerobically. This group represents an excellent system for studying the evolution of parasitism and anaerobic, mitochondrion-related organelles. Understanding these evolutionary transitions requires a well-resolved phylogeny of diplomonads, retortamonads and CLOs. Unfortunately, until now the deep relationships amongst these taxa were unresolved due to limited data for almost all of the CLO lineages. To address this, we assembled a dataset of up to six protein-coding genes that includes representatives from all six CLO lineages, and complements existing rRNA datasets. Multigene phylogenetic analyses place CLOs as well as the retortamonad Chilomastix as a paraphyletic basal assemblage to the lineage comprising diplomonads and the retortamonad Retortamonas. In particular, the CLO Dysnectes was shown to be the closest relative of the diplomonads + Retortamonas clade, with strong support. This phylogeny is consistent with a drastic degeneration of mitochondrion-related organelles during the evolution from a free-living organism resembling extant CLOs to a probable parasite/commensal common ancestor of diplomonads and Retortamonas.


Immunoprecipitation of 125I-insulin crosslinked receptor.
125I-insulin was covalently crosslinked to its receptor on human placental membrane fractions with disuccinimidyl suberate. The 125I-insulin crosslinked receptor was solubilized with Triton X-100 and used as a probe to determine autoantibodies to the insulin receptor in sera from patients with insulin resistance (type B syndrome). When the solubilized 125I-insulin: receptor complex was incubated with these sera and then with anti-human IgG serum, the complex was precipitated as a function of the amount of anti-receptor serum. Unlabelled insulin at concentrations less than or equal to 10 micrograms/ml did not affect immunoprecipitation of the complex, suggesting that a subpopulation of anti-receptor antibodies recognizes determinants outside the insulin binding region of the receptor molecule. 125I-insulin: receptor complex was precipitated also by the addition of anti-insulin antibodies. The effect of anti-insulin antibody was eliminated by the addition of excess unlabelled insulin. The immunoprecipitation assay using 125I-insulin crosslinked receptor was sensitive and convenient for detecting anti-receptor antibodies.


Structural modeling analysis of prospective risk factors for eating disorder.
Many variables have been suggested as possible risk factors for eating disorders (ED), although the validity of these suggestions has seldom been tested causally. The current study tested a pathway model for the development of ED using prospective data from a randomly selected sample of 807 women, aged 18-32 years, from the general population of Sweden. Data was collected using self-report questionnaires with well-established psychometric properties. The cardinal symptoms of binge eating, purging, and fear of weight gain according to the DSM-IV characterized ED. Data supported the hypothesized model suggesting that low self-esteem, low perceived social support from the family, high levels of body concern, and high relative use of escape avoidance coping constitute a risk profile for later development of ED. Given the results and the fact that these risk factors can be modified, their practical utility and clinical significance should be examined in prevention studies.


Stoichiometric relationship between Na(+) ions transported and glucose consumed in human erythrocytes: Bayesian analysis of (23)Na and (13)C NMR time course data.
We examined the response of Na(+),K(+)-ATPase (NKA) to monensin, a Na(+) ionophore, with and without ouabain, an NKA inhibitor, in suspensions of human erythrocytes (red blood cells). A combination of (13)C and (23)Na NMR methods allowed the recording of intra- and extracellular Na(+), and (13)C-labeled glucose time courses. The net influx of Na(+) and the consumption of glucose were measured with and without NKA inhibited by ouabain. A Bayesian analysis was used to determine probability distributions of the parameter values of a minimalist mathematical model of the kinetics involved, and then used to infer the rates of Na(+) transported and glucose consumed. It was estimated that the numerical relationship between the number of Na(+) ions transported by NKA per molecule of glucose consumed by a red blood cell was close to the ratio 6.0:1.0, agreeing with theoretical prediction.


Nuclear triiodothyronine receptor of human adipose tissue.
L-Triiodothyronine induces malic enzyme in explants from human adipose tissue. Consequently, we looked for the presence of receptors for L-triiodothyronine in nuclei isolated from human adipose tissue. The binding of 125I-triiodothyronine by the nuclei was time- and temperature-dependent. At 37 degrees C binding reached a steady state after 60 minutes. Dithiothreitol enhanced total binding and suppressed nonspecific binding. Scatchard analysis showed the presence of a single class of binding sites. The apparent association constant, Ka, was 0.13 +/- 0.03 X 10(10) M-1, the maximal binding capacity 2.20 +/- 0.81 pmol/mg DNA (mean +/- SD, n = 7) and the number of binding sites 8,000/nucleus. L-Triiodothyronine and D-triiodothyronine had equal affinity to the nuclear receptor; triiodothyroacetic acid had three times higher affinity. L- and D-thyroxine had 8% and 12%, respectively, and tetraiodothyroacetic acid had 19% affinity compared to that of L-triiodothyronine. Reverse triiodothyronine was a weak competitor. Digestion of nuclei with micrococcal nuclease abolished specific binding. These results show that nuclei from human white adipose tissue possess high affinity receptors for L-triiodothyronine, which are associated with nuclear chromatin. It is likely that induction of malic enzyme in human adipose tissue by L-triiodothyronine is mediated by the nuclear receptors.


[Bilateral adnexal masses in a pregnant woman--laparoscopic management].
A case of a 30 years old pregnant woman suffering from bilateral ovary tumour was presented. When she was sixteen weeks pregnant she had both tumours enucleated using the method of laparoscopy. Diagnostic and therapeutic process have been described. Authors are convinced that laparoscopy as a method of treatment can be safely applied to pregnant women provided, that specific rules are obeyed and elaborate precautions during the surgery are taken.


Cultural heritage through the lens of COVID-19.
This study examines the discourse emerging from cultural heritage content shared online during the COVID-19 pandemic. It aims to understand the different affective and cognitive dynamics that are associated with the online sharing of cultural heritage in difficult times. To do so, we analyzed two Instagram hashtags-#ShareOurHeritage and #ShareCulture - that are promoted by UNESCO on a global scale. We applied a comprehensive quantitative method for qualitative data analysis. This method relied on Latent Dirichlet Allocation for topic modeling to generate automated induction of semantic topics and understand the underlying cognitive and affective dimensions of Instagram posts under each topic. Social values- including safety, inclusion, participation, and resilience - positive emotional language, and diverse cultural expressions were the most shared by the investigated hashtag community during the COVID-19 pandemic. In addition, results showed that users approach the virtual space as a substitute for the loss of their physical place through terms like home, virtual, online, travel tomorrow, and museums from home. Results are discussed in the context of the global digital divide, the social value of heritage to hashtag communities, and the use of Instagram as a longitudinal record of how cultural heritage values change across time.


Glutamine synthetase becomes nitrated and its activity is reduced during repetitive seizure activity in the pentylentetrazole model of epilepsy.
The astrocyte-specific glutamine synthetase (GS) plays a key role in glutamate recycling and Gamma-aminobutyric acid (GABA) metabolism. Changes in the expression or activity of GS have been proposed to contribute to epileptogenesis. The mechanisms or how and where GS may contribute to epilepsy is still a matter of discussion. Here we asked the question whether brain regions, which show an astrocytic stress response respond with alterations of GS. Biochemical and histological alterations of GS, HSP-27, and GFAP were studied after pentylenetetrazole-induced repetitive epileptic seizures (PIRS) in rats using a topographical quantification of the GS-immunoreactivity (GSIR) in relation to the focal heat shock response (HSR). Saline-treated rats served as controls and rats treated by the GS-inhibitor, L-methionine-sulfoximine (MSO) served as a positive control. No changes in the amount of GSIR and GS-protein occurred during PIRS. A significant reduction of GSIR was observed by histochemistry (in situ) and in native (nonheated) protein extracts of MSO-treated rats. In rats affected by PIRS, GS-activity showed a significant, region-specific reduction in association with a nitration of the enzyme. These results show that neither PIRS nor GS-inhibition reduced the amount of GS protein, but that MSO interferes with antibody binding to native GS. PIRS resulted in a focal increase of astrocytic stress response, whereas MSO caused a widespread, homogeneous astrocytic HSR independent from quantitative changes of GS content. In rats with PIRS the regions showing a strong glial HSR, respond with reduced GS-activity and GS-nitration, which all together are clear indicators of a nitrosative stress response.


Epstein-Barr virus growth/latency III program alters cellular microRNA expression.
The Epstein-Barr virus (EBV) is associated with lymphoid and epithelial cancers. Initial EBV infection alters lymphocyte gene expression, inducing cellular proliferation and differentiation as the virus transitions through consecutive latency transcription programs. Cellular microRNAs (miRNAs) are important regulators of signaling pathways and are implicated in carcinogenesis. The extent to which EBV exploits cellular miRNAs is unknown. Using micro-array analysis and quantitative PCR, we demonstrate differential expression of cellular miRNAs in type III versus type I EBV latency including elevated expression of miR-21, miR-23a, miR-24, miR-27a, miR-34a, miR-146a and b, and miR-155. In contrast, miR-28 expression was found to be lower in type III latency. The EBV-mediated regulation of cellular miRNAs may contribute to EBV signaling and associated cancers.


Insight into Crosstalk Between Mitophagy and Apoptosis/Necroptosis: Mechanisms and Clinical Applications in Ischemic Stroke.
Ischemic stroke is a serious cerebrovascular disease with high morbidity and mortality. As a result of ischemia-reperfusion, a cascade of pathophysiological responses is triggered by the imbalance in metabolic supply and demand, resulting in cell loss. These cellular injuries follow various molecular mechanisms solely or in combination with this disorder. Mitochondria play a driving role in the pathophysiological processes of ischemic stroke. Once ischemic stroke occurs, damaged cells would respond to such stress through mitophagy. Mitophagy is known as a conservatively selective autophagy, contributing to the removal of excessive protein aggregates and damaged intracellular components, as well as aging mitochondria. Moderate mitophagy may exert neuroprotection against stroke. Several pathways associated with the mitochondrial network collectively contribute to recovering the homeostasis of the neurovascular unit. However, excessive mitophagy would also promote ischemia-reperfusion injury. Therefore, mitophagy is a double-edged sword, which suggests that maximizing the benefits of mitophagy is one of the direction of future efforts. This review emphasized the role of mitophagy in ischemic stroke, and highlighted the crosstalk between mitophagy and apoptosis/necroptosis.


Polymorphisms at the paraoxonase 1 L55M and Q192R loci affect the pathophysiology of Alzheimer's disease: emphasis on the cholinergic system and beta-amyloid levels.
Paraoxonase 1 (PON1) functions to protect the cholinergic system against nerve gases and the organophosphate family of pesticides. Recent studies have shown that polymorphisms at the PON1 L55M and Q192R loci might affect individual susceptibility to experience-derived and environmental events such as the exposure to inhibitors of cholinesterase (ChEIs). ChEI therapy being the treatment of choice for mild-to-moderate Alzheimer's disease (AD) patients, we determined whether genetic variations in the PON1 loci are associated with AD risk and whether they affect brain choline acetyltransferase (CHAT) activity, nicotinic receptor density, and beta-amyloid (Abeta) levels in different regions of AD and age-matched control subjects. This pilot genetic study used a small cohort of brains from autopsy-confirmed AD patients and age-matched controls from the Douglas Hospital Brain Bank, Quebec, Canada. The frequency of the M55M genotype at the PON1 L55M locus was found to be significantly increased in AD patients relative to age-matched controls (p < 0.05). Significant associations were observed between the PON1 L55M and Q192R polymorphisms and frontal cortex Abeta levels as well as CHAT activity and nicotinic receptor density in the temporal cortex. Our results suggest a prominent role for PON1 in the pathophysiology of common AD with a marked impact on the cholinergic system and Abeta levels in the brain.


Inactivation of African horse-sickness virus by betapropiolactone and by pH.
The inactivation of several types of African horse sickness virus (AHSV) by pH and by betapropiolactone (BPL) was studied. At 19 degrees - 22 degrees C the virus was stable between pH 6.0 and 10.4, whether suspended in mouse brain or in serumfree buffer. Below pH 5.6 and above pH 10.9, more than 99 per cent of infectivity was inactivated within 15 minutes. The addition of 50 per cent serum did not influence pH stability. Disinfection in the presence of citric acid and caustic soda is briefly discussed. Inactivation by BPL was complete within 30 minutes at 37 degrees C, yet incomplete after 15 hours at 4 degrees C. Types 3 and 9 virus grown in suckling mouse brain and types 1, 3 and 9 produced in pig kidney cells were equally susceptible to 0.1 per cent BPL, more than 99.9 per cent being inactivated. The effectiveness of BPL was reduced at least 10-fold by the addition of 50 per cent serum. No infective virus was detected following incubation of either tissue culture virus with 0.2 per cent BPL or of mouse brain virus with 0.3 per cent BPL. Virus suspensions exposed to 0.3 per cent BPL required buffering with Tris of at least 0.05 molar strength in order to maintain the pH within an acceptable range. Inactivated antigens prepared with 0.4 per cent or lower concentrations of BPL were immunogenic in guinea pigs.


Child with adenylosuccinate lyase deficiency caused by a novel complex heterozygous mutation in the ADSL gene: A case report.
Adenylosuccinate lyase (ADSL) deficiency is a rare autosomal-recessive defect of purine metabolism caused by mutation of the ADSL gene. It can cause severe neurological impairment and diverse clinical manifestations, including epilepsy. Here, we describe a 3-year-old Chinese boy who had both psychomotor retardation and refractory epilepsy. Magnetic resonance imaging showed myelin hypoplasia. Electroencephalography findings supported a diagnosis of epilepsy. Whole-exon sequencing revealed the presence of a novel complex heterozygous mutation in the ADSL gene: The splicing mutation c.154-3C>G and the missense mutation c.71C>T (p. Pro24Leu). Considering the patient's clinical presentation and genetic test results, the complex heterozygous mutation was predicted to prevent both ADSL alleles from producing normal ADSL, which may have led to ADSL deficiency. Finally, the child was diagnosed with ADSL deficiency. We identified a novel complex heterozygous mutation in the ADSL gene associated with ADSL deficiency, thus expanding the known spectrum of pathogenic mutations that cause ADSL deficiency. Additionally, we describe epilepsy that occurs in patients with ADSL deficiency.