Tau glycation is involved in aggregation of the protein but not in the formation of filaments.
A tau peptide, peptide 2R, with capacity for self assembly into filaments was used as a model to test the role of glycation on tau assembly or aggregation. Our results indicate that glycation of that peptide facilitates dimer formation but not assembly into filaments. However, glycation of tau results in the bundling of the tau filaments formed by glycosaminoglycan-induced polymerisation. These results suggest a role of glycation in the formation of covalent links among pre-formed filaments but not in the assembly of those filaments.


The brain-immune axis: role of opiates and other substances of abuse, the hypothalamic-pituitary-adrenal axis and behavior.
The brain-immune axis is a highly complex and dynamic homeostatic mechanism. The effect of morphine, or other drugs of abuse, on this interactive system can have multiple consequences, depending on the specific site(s) of action, duration of exposure and underlying neuroendocrine, neural and behavioral status. This emphasizes the critical role of interdisciplinary studies, incorporating behavioral, pharmacological, neuroanatomical, cellular and molecular approaches, that are necessary for elucidating opiate-BIA interactions. To characterize fundamental mechanisms of action, the sheer complexity of this system often requires that more rigorous experimental methodology be applied by multidisciplinary groups of investigators than ever before.


Vortex structure in Wigner molecules.
We study clusters of vortices for Wigner molecules formed in the laboratory frame induced by anisotropy of the external potential or electron effective mass. For anisotropic systems the ground-state vortex structure undergoes a continuous evolution when the magnetic field is varied in contrast to isotropic systems where it changes rapidly at angular momentum transitions. In fractional quantum Hall conditions the additional vortices first appear on the edges of the confined system far from the axis of a linear Wigner molecule and then approach the electron positions in growing magnetic field. For an isotropic mass the vortices tend to stay at the line perpendicular to the Wigner molecule axis and pass to the axis for the lowest Landau level filling factor of [Formula: see text]. In phosphorene the behaviour of the vortices is influenced by a strong anisotropy of the electron effective mass. The vortices are stabilized off the axis of the molecule when it is oriented along the armchair crystal direction. For the molecule oriented along the zigzag direction the vortices are transfered to the molecule axis already at [Formula: see text]. The transfer is associated with an antivortex creation and annihilation near the electron position.


Resynchrony of previously anoestrous cows and treatment of cows not detected in oestrus that had a palpable corpus luteum with prostaglandin F(2 alpha).
To determine if resynchrony, using a progesterone (P4) / oestradiol benzoate (ODB) regime, of previously treated, anovulatory anoestrous (AA) cows would increase the probability of oestrus, conception and pregnancy compared to no resynchrony. Additionally, the effect of prostaglandin F2alpha (PG) treatment of cows not detected in oestrus, but in which a corpus luteum (CL) was palpable transrectally (NDO/CL+), was compared with no treatment. Cows not detected in oestrus by 1 week before the start of the seasonal breeding programme were categorised as AA or NDO/CL+, based on absence or presence of a palpable CL, respectively. All AA cows were treated with an intravaginal device containing 1.36 g P4 (CIDR-B) for a period of 6 days, and with 1 mg ODB by intramuscular (I/M) injection 1 day after the device was removed (Day 0). Half the AA cows that were detected in oestrus between Days 0 and 3 were randomly assigned to be resynchronised by reinsertion of a clean used CIDR-B device on Day 15, for a period of 6 days, followed by an I/M injection of 0.5 mg ODB, 1 day after the device was removed (resynchrony, RS), while the other half were not resynchronised (no-RS). NDO/CL+ cows were alternately assigned to be either treated with 25 mg of the PG, dinoprost tromethamine, on Day 0 or left as untreated controls (Con). Resynchrony increased the percentage of cows detected in oestrus between Days 14 and 28 (212/282 = 75.2% vs 155/285 = 54.4%, for RS vs no-RS, respectively; p<0.001), but had no effect on conception rate to a service within the first 3 days of the mating period (146/397 = 36.8% vs 148/399= 37.1%, for RS vs no-RS cows, respectively; p>0.9), or to a service between Days 14 and 28 (84/159 = 52.8% vs 114/217 = 52.5%, for RS vs no-RS cows, respectively; p>0.9). Resynchrony increased the Day 28 pregnancy rate (264/432 = 61.1% vs 237/435 = 54.5%, for RS vs no-RS cows, respectively; p=0.03), but had no effect on the Day 56 or final pregnancy rates (p>0.1).Prostaglandin treatment of NDO/CL+ cows did not affect the percentage of cows detected in oestrus by Day 7 (43/106 = 40.6% vs 51/101 = 50.5%, for Con vs PG, respectively; p=0.15), or Day 28 (92/106 = 86.8% vs 91/101 = 90.1%, for Con vs PG, respectively; p>0.4). Treatment did not affect the Day 28 pregnancy rate (55/103 = 53.4% vs 54/98 = 55.1%, for Con vs PG, respectively; p>0.9), the Day 56 pregnancy rate (81/103 = 78.6% vs 74/98 = 75.5%, for Con vs PG, respectively; p>0.6), or the final pregnancy rate (98/103 = 95.1% vs 89/97 = 91.8%, for Con vs PG, respectively; p>0.3). Resynchrony of AA cows treated using the present protocol increased the proportion of non-pregnant cows detected in oestrus between Days 14 and 28 and increased the Day 28 pregnancy rate. This resynchrony protocol may be useful for increasing the proportion of the herd pregnant in the first month of the breeding programme, especially in herds that have a history of a low proportion of non-pregnant cows detected in oestrus between Days 14 and 28. There was no benefit in treating NDO/CL+ cows with PG compared to no treatment.


Rebamipide increases barrier function and attenuates TNFα-induced barrier disruption and cytokine expression in human corneal epithelial cells.
Disruption of corneal epithelial barrier function by inflammation may contribute to the development of dry eye. The effects of rebamipide, a drug used for the treatment of dry eye, on barrier function and cytokine expression in a human corneal epithelial (HCE) cell line were examined. Barrier function of HCE cells was evaluated by measurement of transepithelial electrical resistance (TER). The subcellular localisation of the tight junction protein zonula occludens (ZO)-1 was examined by immunofluorescence analysis. The release of cytokines was determined with ELISAs, and the intracellular abundance of cytokine mRNAs was quantitated by reverse transcription and real-time PCR analysis. Degradation of the nuclear factor-κB inhibitor IκBα was detected by immunoblot analysis. Rebamipide increased TER of HCE cells in a concentration-dependent manner as well as attenuating the loss of TER and the disappearance of ZO-1 from the cell surface induced by tumour necrosis factor α (TNFα). Rebamipide also suppressed TNFα-induced expression of interleukin-6 and interleukin-8 at the mRNA and protein levels and inhibited the TNFα-induced degradation of IκBα. The upregulation of barrier function and the anti-inflammatory effects of rebamipide, together with its mucin secretagogue activity, may contribute to the effectiveness of this drug for the treatment of dry eye.


Evaluation of arginine deiminase treatment in melanoma xenografts using (18)F-FLT PET.
This study aims to develop a molecular imaging strategy for response assessment of arginine deiminase (ADI) treatment in melanoma xenografts using 3'-[(18)F]fluoro-3'-deoxythymidine ([(18)F]-FLT) positron emission tomography (PET). F-FLT response to ADI therapy was studied in preclinical models of melanoma in vitro and in vivo. The molecular mechanism of response to ADI therapy was investigated, with a particular emphasis on biological pathways known to regulate (18)F-FLT metabolism. Proliferation of SK-MEL-28 melanoma tumors was potently inhibited by ADI treatment. However, no metabolic response was observed in FLT PET, presumably based on the known ADI-induced degradation of PTEN, followed by instability of the tumor suppressor p53 and a relative overexpression of thymidine kinase 1, the enzyme mainly responsible for intracellular FLT processing. The specific pharmacological properties of ADI preclude using (18)F-FLT to evaluate clinical response in melanoma and argue for further studies to explore the use of other clinically applicable PET tracers in ADI treatment.


Tuberculosis among Africans living in the United States, 2000-2009.
The incidence of tuberculosis (TB) has declined steadily in the United States; however, foreign-born persons are disproportionately affected. The aim of our study was to describe characteristics of TB patients diagnosed in the United States who originated from the African continent. Using data from the U.S. National Tuberculosis Surveillance System, we calculated TB case rates and analyzed differences between foreign-born patients from Africa compared with other foreign-born and U.S.-born patients. The 2009 TB case rate among Africans (48.1/100,000) was 3 times as high as among other foreign-born and 27 times as high as among U.S.-born patients. Africans living in the United States have high rates of TB disease; they are more likely to be HIV-positive and to have extrapulmonary TB. Identification and treatment of latent TB infection, HIV testing and treatment, and a high index of suspicion for extrapulmonary TB are needed to better address TB in this population.


Variants of Takotsubo syndrome in the perioperative period: A review of potential mechanisms and anaesthetic implications.
Takotsubo syndrome (TS) is a condition of transient cardiac dysfunction that develops in the setting of abrupt sympathetic stimulation. Although classically identified by ballooning of the apical segment, TS can also present in atypical forms with abnormalities of the basal, mid-ventricular, or other focal segments. In the perioperative setting, anaesthetic effects and physiologic perturbations from surgery can further confound the diagnosis. We present a narrative review of the most recent evidence for underlying pathophysiologic mechanisms of the variable ballooning patterns and highlight important anaesthetic considerations in the diagnosis and management of these patients.


Bilateral solar retinopathy. Autofluorescence and optical coherence tomography.
A 33-year-old man referred decreased bilateral visual acuity for five years, with no history of interest. Military profession and probably previous sun exposure. Focal pigmented lesions in the macular area of the fundus were observed, with impairment of the photoreceptor layer in the fovea, observed by optical coherence tomography (OCT), in various sectors of the fovea. Solar retinopathy is associated with professions at risk of sun exposure. The diagnosis is based on autofluorescence and macular OCT, that later will provide key data to establish the cause.


Low-dose levetiracetam for seizure prophylaxis after traumatic brain injury.
The primary objective of this study was to determine the effectiveness of a lower dose of levetiracetam (500 mg every 12 hours) to prevent early seizures after traumatic brain injury (TBI). It was hypothesized that the seizure rate would be low and comparable to previous studies using phenytoin. This was a retrospective cohort study conducted in a tertiary care, academic institution that is designated as a level 1 trauma centre in the US. Consecutive patients with TBI were evaluated. Patients who were given a levetiracetam dose of 500 mg every 12 hours were included. The primary outcome was the occurrence of a seizure within 7 days of TBI. There were a total of 169 patients included in the study, who were treated with levetiracetam 500 mg every 12 hours. The median time to first dose of levetiracetam was 3.5 hours after injury (interquartile range = 1-13 hours). After initiation of levetiracetam, there were four (2.4%) patients who had a seizure within 7 days. This was not significantly different than the hypothesized population value of 3.6% (p = 0.390). A lower dose of levetiracetam 500 mg every 12 hours after TBI may be effective for early seizure prevention after TBI.


Radiation therapy for cT1-2 carcinoma of the palatine tonsil diagnosed via a simple tonsillectomy: Dosimetry and patterns of care in the IMRT era.
Small carcinomas of the palatine tonsil are often diagnosed via simple tonsillectomy, a maneuver with non-therapeutic intent. Herein, practice patterns for this unique situation are evaluated. A retrospective review was performed across 10 facilities to identify patients with cT1-2 squamous carcinomas of the tonsil diagnosed by simple tonsillectomy between 2010 and 2018. Patients who received curative-intent intensity modulated radiotherapy (IMRT) without additional surgery were included. Target volumes were reviewed, and cumulative incidences of local failure and severe late dysphagia were calculated. From 638 oropharyngeal patients, 91 were diagnosed via simple tonsillectomy. Definitive IMRT with no additional surgery to the primary site was utilized in 57, and three with gross residual disease were excluded, leaving 54 for analysis. Margins were negative in 13%, close (<5 mm) in 13%, microscopically positive in 61%, and not reported in 13%. Doses typically delivered to gross disease (68-70.2 Gy in 33-35 fx or 66 Gy/30 fx) were prescribed to the tonsil bed in 37 (69%). Sixteen patients (29%) received doses from 60 to 66 Gy (≤2 Gy/fx) and one received 50 Gy (2 Gy/fx). No local failures were observed. One late oropharyngeal soft tissue ulcer occurred, treated conservatively (grade 2). At five years, the cumulative incidence of severe late dysphagia was 17.4% (95% CI 6.1-28.8%). Small tonsil carcinomas diagnosed by simple tonsillectomy represent a niche subset with favorable oncologic outcomes. Regardless, radiation oncologists tend to deliver full-dose to the tonsil bed. The necessity of this routine could be questioned in the modern era.


Two-Year Trajectory of Fall Risk in People With Parkinson Disease: A Latent Class Analysis.
To examine fall risk trajectories occurring naturally in a sample of individuals with early to middle stage Parkinson disease (PD). Latent class analysis, specifically growth mixture modeling (GMM), of longitudinal fall risk trajectories. Assessments were conducted at 1 of 4 universities. Community-dwelling participants with PD of a longitudinal cohort study who attended at least 2 of 5 assessments over a 2-year follow-up period (N=230). Not applicable. Fall risk trajectory (low, medium, or high risk) and stability of fall risk trajectory (stable or fluctuating). Fall risk was determined at 6 monthly intervals using a simple clinical tool based on fall history, freezing of gait, and gait speed. The GMM optimally grouped participants into 3 fall risk trajectories that closely mirrored baseline fall risk status (P=.001). The high fall risk trajectory was most common (42.6%) and included participants with longer and more severe disease and with higher postural instability and gait disability (PIGD) scores than the low and medium fall risk trajectories (P<.001). Fluctuating fall risk (posterior probability <0.8 of belonging to any trajectory) was found in only 22.6% of the sample, most commonly among individuals who were transitioning to PIGD predominance. Regardless of their baseline characteristics, most participants had clear and stable fall risk trajectories over 2 years. Further investigation is required to determine whether interventions to improve gait and balance may improve fall risk trajectories in people with PD.


A case report of umbilical ring constriction with application of amnioinfusion.
This is a case report of a pregnant 38-year-old primigravida woman. Due to severe fetal growth restriction and oligohydramnios, she was referred to our tertiary perinatal center at 24 weeks' gestation. To rule out chromosomal abnormalities and facilitate ultrasound evaluation of fetal morphology, we performed amniocentesis and subsequent amnioinfusion. Thereafter, a precise ultrasound examination revealed no obvious fetal morphological abnormalities except for a hyper-coiled cord and marginal placenta previa. During expectant management, the amount of amniotic fluid was maintained at 20-26 mm for a few days; however, the pregnancy resulted in intrauterine fetal death after 26 weeks + 5 days of gestation. The stillborn infant weighed 530 g (-3.3 SD) and had no obvious external abnormalities apart from umbilical ring constriction. Although a postmortem autopsy was not performed, it is suspected that the fetal growth restriction and the intrauterine fetal death were associated with the hyper-coiled cord and the umbilical ring constriction. It is thought that umbilical ring constriction might therefore be an irreversible fatal condition in cases with a hyper-coiled cord.


[Immune proteasomes in the developing rat spleen].
Changes in the structure of the rat spleen and the distribution of immune proteasomes in it during early postnatal development have been studied using double immunofluorescent staining of tissue sections with antibodies to the LMP7 immune proteasome subunit and to specific markers of T and B lymphocytes. It has been shown that the white pulp on postnatal day 5 is not yet colonized by lymphocytes and contains a smaller amount of immune proteasomes than the red pulp. At this stage, T and B lymphocytes concentrate mainly in the red pulp. On day 8, B lymphocytes occupy the marginal zone, while T lymphocytes aggregate into dense strands close to the white pulp. By day 18, T lymphocytes form periarteriolar sheaths in the white pulp, and the contents of immune proteasomes in the red and white pulp become equally high. An increase in the total content of immune proteasomes in the spleen on the third postnatal week was revealed in our previous study by Western blotting. In addition to T and B lymphocytes, immune proteasomes have also been revealed in other spleen cell types, probably in macrophages and reticular cells of the white pulp. Thus, the postnatal development of the spleen is associated with an increase in the contents of immune proteasomes in it.


A monoclonal antibody to the human epidermal growth factor receptor.
A monoclonal antibody of the IgG class, EGFR1, has been isolated using cells of the epidermoid carcinoma line A431 as immunogen. The A431 antigen recognized by EGFR1 has an apparent molecular weight of approximately 175,000, is a cell-surface molecule which can be specifically cross-linked to EGF, exhibits an EGF-stimulated protein kinase activity, binds to EGFR1 in a number of human cell lines to a degree which parallels EGF binding, and shows EGF-dependent internalization in A431 cells and human fibroblasts. We therefore conclude that EGFR1 is directed against an antigenic site on the human EGF receptor. EGFR1 is not mitogenic for human fibroblasts and does not inhibit EGF binding under a variety of assay conditions. The characterization of EGFR1 has allowed the unambiguous assignment of the structural gene for the human EGF receptor to chromosome 7. Preliminary results suggest that a convenient method for isolating a range of anti-EGF receptor monoclonal antibodies can be developed, based on a hybridoma supernatant screening assay in which positive supernatants bind selectively to a human-mouse cell hybrid containing human chromosome 7.


Reirradiation: A complex situation.
Reirradiation of a tumor recurrence or second cancer in a previously irradiated area is challenging due to lack of high-quality physical, radiobiological, clinical data and inherent substantial risks of toxicity with cumulative dose and uncertain tissue recovery. Yet, major advances have been made in radiotherapy techniques, that have the potential to achieve cure while limiting severe toxicity rates, but still much research is necessary to better appraise the therapeutic index in such a complex situation.


In vivo oxymetric analysis of mild hypercapnia upon cerebral oxygen, temperature and blood flow: markers of mood as proposed by concomitant bupropion challenge and electrochemical analysis?
Scientific interest has increased the influence of temperature in neurodegenerative and psychiatric disorders, and according to the monoamine hypothesis, depression is a neurochemical disorder arising from hypofunctioning of brain monoamine systems. Here, in vivo flow-oxymetry is applied to verify relationships between cerebral oxygen tension (pO2), blood flow (CBF), that are markers of brain metabolism, and temperature (T), while in vivo voltammetry is concomitantly applied in the medial prefrontal cortex of anaesthetized rats to monitor monoamine levels such as dopamine (DA) and serotonin. An induced mild hypercapnia via increasing exogenous carbon dioxide (CO2) concentration resulted in increased pO2, CBF and T in discrete brain areas. Concomitant in situ voltammetric analysis of extracellular levels of serotonin and DA has revealed significant changes in the latter, only. Parallel treatment with antidepressant bupropion has confirmed its described central thermogenic properties and its positive influence on dopaminergic activity. CBF was also enhanced by such antidepressant. Altogether these data support direct relationships between markers of brain metabolism such as pO2, CBF, T and brain monoamine[s], indicating the coupled in vivo methodology: oxymetry-voltammetry as a rapid in vivo tool for analyses of such indicators in psychiatric disorders.


Highly photosensitive colorimetric immunoassay for tumor marker detection based on Cu2+ doped Ag-AgI nanocomposite.
Visual detection of tumor markers with accuracy and selectivity exhibits significant advantages for cancer early diagnosis due to its low-cost and simple analytical instruments. Herein, a highly photosensitive colorimetric immunoassay for carcino embryonie antigen (CEA, as a model) detection based on Cu2+ doped Ag-AgI nanocomposite was constructed. First, Cu2+ doped Ag-AgI nanocomposite (Cu2+/Ag-AgI) owned the ability of oxidization of TMB was synthesized by impregnation method, which was characterized by transmission electron microscope (TEM), scanning electron microscope (SEM), energy-dispersive X-ray spectroscopy (EDX), X-ray powder diffraction (XRD), UV-Vis diffuse reflectance spectroscopy (DRS) and X-ray photoelectron spectroscopy (XPS). Second, based on sandwich-type immunoassay, the immunocomplex was built on the surface of magnetic bead by utilizing Cu2+/Ag-AgI as labels. The blue color of TMBox was obtained under visible irradiation and ultraviolet spectrum scanning was carried out in ABS buffer solution. Under optimal conditions, the absorbance values increased with the increasing of CEA concentrations in sample with the linearity range of 1.0pgmL-1-5.0ngmL-1. The detection limit was 0.13pgmL-1. More importantly, the developed colorimetric immunoassay exhibited good selectivity, repeatability, stability and possible applications in the real serum sample analysis.


My life with Yersinia.
This review is based on the opening lecture I was honored to give during the 9th International Symposium on Yersinia in Lexington, Kentucky in October 2006. I present some topics that have been close to my interest during the past 25 years with some historical anecdotes. For example, how detection of intervening sequences in Yersinia enterocolitica rDNA genes resulted in development of microbial diagnostic applications. How the adhesin YadA was detected and named and what do we know of its function now? What was the first pseudogene sequenced in Yersinia pestis? I will also discuss Yersinia lipopolysaccharide, bacteriophages and serum resistance mechanisms which we have worked on lately.


Superoxide dismutase activity of normal murine liver, regenerating liver, and H6 hepatoma.
By means of both direct assay and gel electrophoresis, normal A/J mouse liver was shown to possess both Cu-Zn and Mn superoxide dismutase (SD) activity. H6 hepatoma cells contained Cu-Zn SD activity, but no Mn SD activity was detectable. Isolated mitochondria from normal liver contained both forms of the enzyme, but isolated mitochondria from H6 hepatoma cells contained no SD activity. To ascertain whether this loss of Mn SD activity was characteristic of these tumor cells or was simply a property of rapidly dividing cells, SD activity was measured in regenerating liver. Mn SD activity was present in the regenerating liver at all times after surgery. Hence loss of the Mn SD activity seemed to be a characteristic of some tumor cells but not of corresponding rapidly dividing normal cells.


The insulin receptor of adult heart muscle cells.
Isolated cardiac myocytes possess specific receptors for insulin which consist of high- and low-affinity sites and are randomly distributed at the cell surface at 37 degrees C. Low-affinity sites can mediate a biological response comparable to that of high-affinity sites. Calcium appears to modulate the high-affinity site and thus may be involved in the regulation of cardiac sensitivity towards insulin. The data suggest involvement of the insulin receptor in insulin degradation, which includes internalization and lysosomal processing of insulin.


Systemic and mucosal antibody response of freshwater cultured Asian seabass (Lates calcarifer) to monovalent and bivalent vaccines against Streptococcus agalactiae and Streptococcus iniae.
Asian seabass, Lates calcarifer farming in Southeast Asia, encounters serious disease challenges caused by Streptococcus agalactiae and Streptococcus iniae. However, a vaccine for disease prevention is not yet available. In this study, we investigated the mucosal and systemic antibody (IgM) response kinetics of the Asian seabass following primary immunization with oil-based formalin-killed vaccines (FKVs) prepared from S. agalactiae and S. iniae (monovalent Sa, monovalent Si, and bivalent Sa-Si) and secondary booster with the respective water-based FKVs. The efficacy of vaccines was subsequently evaluated by an experimental challenge. The results revealed similar antibody response kinetics in both systemic and mucosal systems. However, the immune response in the fish vaccinated with the monovalent vaccines was superior to those fish received the bivalent vaccine in terms of specific antibody titer. The fish that received monovalent vaccines required 1-2 weeks to raise a significant level of specific antibody titer in both systemic and mucosal systems while those vaccinated with bivalent vaccine required three weeks. Following booster at day 21, both systemic and mucosal antibody titers in all vaccinated groups had reached the peak at day 28 and gradually declined in the following weeks but remained significantly higher than control until the end of the experiment (day 63). In the challenge test, both monovalent and bivalent vaccines were found to be highly efficacious, with the relative percentage survival (RPS) ranging from 75 to 85%. In summary, this study explored the 63-days antibody response kinetics (both mucosal and systemic systems) of Asian seabass to monovalent and bivalent inactivated vaccines and confirmed that the combination of S. agalactiae and S. iniae in a single injectable vaccine is possible.


Chinese visceral adiposity index: A reliable indicator of visceral fat function associated with risk of type 2 diabetes.
The evidence of the association between Chinese visceral adiposity index (CVAI) and risk of type 2 diabetes mellitus (T2DM) is limited. We explored the association of CVAI with T2DM and directly compared with the predictive power of CVAI with other visceral obesity indices (visceral adiposity index, waist to height ratio, waist circumference and body mass index) based on a large prospective study. We conducted a population-based study of 12 237 Chinese participants. Cox proportional-hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between CVAI and T2DM. During follow-up (median: 6.01 years), the incidence of T2DM was 3.29, 7.34, 12.37 and 23.72 per 1000 person-years for quartiles 1, 2, 3 and 4 of CVAI, respectively. The risk of T2DM was increased with quartiles 2, 3 and 4 vs quartile 1 of CVAI (HR 2.12 [95% CI 1.50-3.00], 2.94 [2.10-4.13] and 5.01 [3.57-7.04], Ptrend < 0.001). Per-SD increase in CVAI was associated with a 72% increased risk of T2DM (HR 1.72 [95% CI 1.56-1.88]). Sensitivity analyses did not alter the association. The area under receiver operating characteristic curve was significantly higher for CVAI than other visceral obesity indices (all P <.001). Similar results were observed in stratified analyses by sex. Our findings show a positive association between CVAI and risk of T2DM. CVAI has the best performance in predicting incident T2DM, so the index might be a reliable and applicable indicator identifying people at high risk of T2DM.


Differing patterns of antiresorptive pharmacotherapy in nursing facility residents and community dwellers.
Little is known about differences between current patterns of antiresorptive therapy (ART) use in nursing facility (NF) residents and by community-dwelling older adults (CDs). ART use was compared in older NF residents and CDs. Cross-sectional analysis. Kansas Medicaid files from May 2000 through April 2001. Women aged 65 and older having at least 9 months of data as a CD or NF resident. Pharmacy claims were used to identify any ART prescription, including hormone replacement therapy (HRT), a bisphosphonate, raloxifene, or calcitonin. Demographic and clinical variables were identified from the claims files. Factors associated with ART use in bivariate analyses were entered into logistic regression models. Similar analyses were performed for bisphosphonate use among non-estrogen replacement therapy (non-ERT) ARTs (excluding HRT). The final study sample (N=2,289) included 898 NF (mean age 85.2) residents and 1,391 CDs (mean age 76.6). CDs were more likely to receive any ART (24.5%) than NF residents (19.6%). After adjustment for potential confounders, NF residents aged 65 to 84 were less likely (odds ratio (OR)=0.61, 95% confidence interval (CI)=0.44-0.85) to receive ART than CDs of the same age. Conversely, of those aged 85 and older, NF residents were more likely than CDs to receive ART (OR=1.96, 95% CI=1.18-3.25). Calcitonin was the most common non-ERT ART prescribed for NF residents, whereas bisphosphonates were more often prescribed for CDs. Underusage of ART is common in NF and CD cohorts. NF residents are less likely to receive bisphosphonates and more likely to receive calcitonin, for which efficacy is less clear. Further research is needed to identify factors influencing ART prescribing and selection of specific ARTs in different settings.


Role of the mitochondrial sodium/calcium exchanger in neuronal physiology and in the pathogenesis of neurological diseases.
In neurons, as in other excitable cells, mitochondria extrude Ca(2+) ions from their matrix in exchange with cytosolic Na(+) ions. This exchange is mediated by a specific transporter located in the inner mitochondrial membrane, the mitochondrial Na(+)/Ca(2+) exchanger (NCX(mito)). The stoichiometry of NCX(mito)-operated Na(+)/Ca(2+) exchange has been the subject of a long controversy, but evidence of an electrogenic 3 Na(+)/1 Ca(2+) exchange is increasing. Although the molecular identity of NCX(mito) is still undetermined, data obtained in our laboratory suggest that besides the long-sought and as yet unfound mitochondrial-specific NCX, the three isoforms of plasmamembrane NCX can contribute to NCX(mito) in neurons and astrocytes. NCX(mito) has a role in controlling neuronal Ca(2+) homeostasis and neuronal bioenergetics. Indeed, by cycling the Ca(2+) ions captured by mitochondria back to the cytosol, NCX(mito) determines a shoulder in neuronal [Ca(2+)](c) responses to neurotransmitters and depolarizing stimuli which may then outlast stimulus duration. This persistent NCX(mito)-dependent Ca(2+) release has a role in post-tetanic potentiation, a form of short-term synaptic plasticity. By controlling [Ca(2+)](m) NCX(mito) regulates the activity of the Ca(2+)-sensitive enzymes pyruvate-, alpha-ketoglutarate- and isocitrate-dehydrogenases and affects the activity of the respiratory chain. Convincing experimental evidence suggests that supraphysiological activation of NCX(mito) contributes to neuronal cell death in the ischemic brain and, in epileptic neurons coping with seizure-induced ion overload, reduces the ability to reestablish normal ionic homeostasis. These data suggest that NCX(mito) could represent an important target for the development of new neurological drugs.


Suppression of foreign innervation in axolotl muscle may not be dependent on juxtaposition of native and foreign nerve terminals.
The posterior supracoracoideus nerve of the axolotl, Ambystoma mexicanum, was induced to make synapses outside its normal muscle territory. Muscle fibres with inputs from both native and foreign nerves were studied during the period of suppression of foreign transmission and in only 8% of fibres were foreign and native terminals found within 120 micrometer of each other. A combined cholinesterase/silver staining technique revealed non-innervated endplates in foreign-innervated fibres just prior to the return of the native nerve. These results suggest a mechanism enabling suppression of foreign synapses at some distance from native synapses probably beginning with the reinnervation of empty sites by the native nerve.


Fungal scleritis with exudative retinal detachment.
To report a case of fungal scleritis associated with exudative retinal detachment. A rare case report. Nonresolving fungal scleritis mimicking noninfective scleritis was treated with systemic and topical antifungals and low topical steroids after diagnosis was established on scleral scraping. Even after complete resolution of scleritis, exudative retinal detachment persisted. The patient was advised of a possible need to undergo vitreo retinal surgery if exudative retinal detachment persisted for more than a month after complete resolution of the scleritis component. Infective scleritis must be ruled out in cases of longstanding scleritis not responding to immunosuppressives.


Effects of dietary genistein on mouse reproduction, postnatal development and weight-regulation.
Genistein is a soy isoflavone with estrogenic activity present in plant-based food items and health foods and used as an alternative therapy for cancer, cardiovascular diseases, menopausal symptoms and osteoporosis. The aim of this study was to investigate the effects of dietary genistein (8 mg/kg body weight/day) on the reproduction, postnatal development and weight regulation of mice across two generations. Genistein treatment decreased the relative food consumption in females at 1 and 5 weeks and in males at 5 weeks. In female pups, the relative kidney weights were lower due to genistein exposure. Furthermore, the genistein-exposed male pups had greater relative prostate and seminal vesicles weights than the control pups. In adult males, genistein treatment decreased the plasma estradiol concentrations and increased levels of the plasma HDL cholesterol and triglycerides in adult females. Also the plasma ghrelin concentrations decreased in the adult genistein treated female mice. Genistein increased the plasma triglyceride levels of male pups and triiodothyronine levels of female pups. Reproduction of the mice was not endangered due to genistein exposure.


Avirulent Semliki Forest virus replication and pathology in the central nervous system is enhanced in IL-12-defective and reduced in IL-4-defective mice: a role for Th1 cells in the protective immunity.
Experimental infection of mice with avirulent Semliki Forest virus (SFV) has been used as a model of demyelinating disease in humans. A number of studies have shown that T cells may be important for mediating demyelination, but the role of T cells is still, unclear. Here, we show that neuronal necrosis, but not demyelination, was more severe in interleukin (IL)-12-defective mice compared with wild-type mice and this correlated with higher virus titers in the brain. In contrast, the severity of demyelination and neuronal depletion was reduced in IL-4-defective mice and this correlated with reduced brain virus titers and enhanced SFV-specific IFN-gamma production. The findings indicate that type 1 T cells play a role in the control of SFV replication but not directly in SFV-induced pathology in the CNS.


Body mass index and the prevalence of prehypertension and hypertension in a Chinese rural population.
To evaluate the status of overweight and obesity in a Chinese rural adult population and describe relationships between body mass index (BMI) and blood pressure according to JNC-7. The study was conducted in 2004-2006, used a multistage cluster sampling method to select a representative sample. A total of 45,925 adults, age 35 years or older, were examined. Height, weight and blood pressure were obtained by trained doctors. Overweight and obesity were defined according to the World Health Organization classification and Chinese definition. The prevalence of overweight and obesity were 16.3% and 1.3% in males, and 24.4% and 2.7% in females (p for gender differences <0.05) according to the World Health Organization classification; The prevalence of overweight and obesity were 29.5% and 5.3% according to the Chinese definition.The prevalence of elevated blood pressure (prehypertension and hypertension) and mean levels of systolic and diastolic blood pressure increased as BMI increased. Multivariate logistic regression revealed that overweight and obesity were risk factors for prehypertension and hypertension whether in males or females. Overweight and obesity has become very prevalent in the Chinese rural adult population. It is a great health problem. Our study quantifies the strong associations of BMI and elevated blood pressure. It is time to pay more attention to overweight and obese in the county of China.


The feasibility of real-time in vivo optical detection of blood-brain barrier disruption with indocyanine green.
Osmotic disruption of the blood-brain barrier (BBB) by intraarterial mannitol injection is sometimes required for the delivery of chemotherapeutic drugs to brain tissue. Osmotic disruption is affected by a number of factors, and there is a significant variability in the degree and distribution of BBB disruption in clinical and experimental settings. Brain tissue concentrations of indocyanine green (ICG) can be measured by optical techniques. The aim of this experiment was to determine whether the disruption of the BBB significantly altered the regional pharmacokinetics of ICG. We were able to track in vivo brain tissue concentrations of ICG in 13 New Zealand white rabbits by employing a novel optical approach. Evan's blue was used to assess the distribution of BBB disruption on post mortem examination. BBB disruption by intraarterial mannitol injection was found to be highly variable, and only five of the 13 animals demonstrated the disruption at the site of optical measurements. In these animals, we observed a ninefold increase in ICG concentrations and fourfold increase in the area under the concentration-time curve, compared to those without BBB disruption at the site of measurement. This study shows the feasibility of optical monitoring of BBB disruption with intravenous (IV) ICG injections. Virtual real-time optical monitoring of the BBB disruption could help improve intraarterial delivery of chemotherapeutic drugs.


Sutureless intrascleral posterior chamber intraocular lens fixation.
We report a technique for sutureless fixation of standard 3-piece posterior chamber intraocular lenses (PC IOLs) in the ciliary sulcus in eyes without capsule support, which we have used in cases of subluxated and luxated cataract and for secondary IOL implantation. Fixation of the haptics in a limbus-parallel scleral tunnel allows exact centration and provides axial stability of the PC IOL to prevent distortion. The technique uses uncomplicated maneuvers for standard 3-piece PC IOL fixation without the need for special haptic architecture or preparation.


Influence of the Substrate to the LSP Coupling Wavelength and Strength.
Three kinds of typical structures, hemi-/spherical nanoparticles/nanoparticle dimers on the substrate and spherical nanoparticles/nanoparticle dimers half-buried into the substrate, are used for FDTD simulation to theoretically discuss the influence of the substrate to the localized surface plasmon (LSP) coupling when the metal nanoparticles/nanoparticle dimers are locating near a substrate. Simulated results show that the dependencies between the LSP coupling wavelength and the refractive index of the substrate for different structures are not the same, which can be attributed to the different polarization field distributions of LSPs. When light is incident from different directions, the LSP coupling strength are not the same as well and the ratios of the scattering peak intensities depend on the position of the metal nanoparticles or nanoparticle dimers. These phenomenon can be explained by the difference of the local driving electric field intensities which is modulated by the interface between the air and the substrate.


Are Patients Interested in Liposomal Bupivacaine as a Nonopioid Alternative for Postsurgical Analgesia Following Third Molar Extractions?
Liposomal bupivacaine (LB) is a long-acting local anesthetic used for postsurgical analgesia to reduce pain and the need for opioid pain medication. The purpose of this study was to assess patient interest in the use of LB as an alternative to opioid pain medication following third molar extraction. A cross-sectional, questionnaire-based study was performed. Study subjects included patients 17 years old or greater who presented to the Oral and Maxillofacial Surgery clinic at Thomas Jefferson University for third molar extraction from May 2019 through January 2020. The primary outcome variable was patient interest in LB, defined by "yes" or "no" from the survey question: "would you be interested in an alternative medication administered during the procedure that may decrease the need for opioid pain medication?". The secondary outcome variable was patient willingness to pay (WTP) for LB, defined by the out-of-pocket cost threshold patients reported they would pay. Covariates included patient demographics, attitudes towards opioid medication, and prior opioid use. Data were analyzed using descriptive statistics, Fisher's exact test, Kruskal-Wallis and Dunn's tests, Kendall's tau correlation, and multivariable logistic regression. Statistical significance was set at P value < .05. A total of 183 subjects completed the study (68% female, 32% male). The mean age was 27.5 years ± 11.1 years. Most subjects (76%) were interested in LB, but 88% had a WTP threshold below $200. Interest in LB was associated with higher WTP thresholds (adjusted odds ratio {aOR} 2.07; 95% confidence interval {CI} [1.48, 3.13]; P < .001). There was also an association between interest and subjects concerned of the addictive potential of opioids (aOR 4.04; 95% CI [1.52, 11.49]; P = .01) and between interest and previous use of prescribed opioid medication (aOR 6.00; 95% CI [1.59, 31.23]; P = .02). Although most subjects were interested in LB, the current out-of-pocket cost of LB appears to be a barrier to patient acceptability. A lower cost option may increase the accessibility and adoption of this nonopioid analgesic for postoperative pain control in third molar extractions.


Potential of Autologous Adipose-Derived Mesenchymal Stem Cells in Peritoneal Fibrosis: A Pilot Study.
We aimed to determine the effects of systemic therapy with autologous adipose tissue derived mesenchymal stem cells (AD-MSCs) on different parameters of peritoneal function and inflammation in peritoneal dialysis (PD) patients. We enrolled nine PD patients with ultrafiltration failure (UFF). Patients received 1.2±0.1×106 cell/kg of AD-MSCs via cubital vein and were then followed for six months at time points of baseline, 3, 6, 12, 16 and 24 weeks after infusion. UNI-PET was performed for assessment of peritoneal characteristics at baseline and weeks 12 and 24. Systemic and peritoneal levels of tumor necrosis factor α (TNF-α), interleukin-6(IL-6), IL-2 and CA125 (by ELISA) and gene expression levels of transforming growth factor beta (TGF-β), smooth muscle actin (𝛼-SMA) and fibroblast-specific protein-1 (FSP-1) in PD effluent derived cells (by quantitative real-time PCR) were measured at baseline and weeks 3, 6, 12, 16 and 24. Slight improvement was observed in the following UF capacity indices: free water transport (FWT, 32%), ultrafiltration - small pore (UFSP, 18%), ultrafiltration total (UFT, 25%), osmotic conductance to glucose (OCG, 25%), D/P creatinine (0.75 to 0.70), and Dt/D0 glucose (0.23 to 0.26). There was a slight increase in systemic and peritoneal levels of CA125 and a slight decrease in gene expression levels of TGF-β, α-SMA and FSP-1 that was more prominent at week 12 and vanished by the end of the study. Our results for the first time showed the potential of MSCs for treatment of peritoneal damage in a clinical trial. Our results could be regarded as hypothesis suggestion and will need confirmation in future studies.


Patient and health care system delays in pulmonary tuberculosis diagnosis in a low-incidence state.
Tuberculosis (TB) patients reported to the Maryland Department of Health and Mental Hygiene from 1 June 2000 to 30 November 2001. To determine the extent of delayed diagnosis of TB and to assess patient and provider factors associated with delays. A prospective cohort study. Median patient, health care and total delays were 32, 26 and 89 days, respectively, for 158 patients. Non-white (relative hazard [RH] 0.62; 95% CI 0.39-0.98) and less educated (RH 0.43; 95% CI 0.26-0.72) patients had longer patient delays. English-speaking patients (RH 0.40; 95% CI 0.24-0.68) had increased health care delays, as did patients who received a diagnosis of a respiratory illness and non-TB antibiotics (RH 0.69; 95% CI 0.49-0.96) prior to a TB diagnosis. Patients first presenting to a private physician (51 days) rather than a hospital emergency room (18 days; RH 1.87; 95% CI 1.05-3.33) or public health clinic (10 days; RH 1.79; 95% CI 1.21-2.63) had longer health care delays. When a TB diagnostic tool (chest radiograph or AFB culture) was utilized, a more rapid diagnosis of TB was made. Education of the patient population about TB symptoms might reduce delays. Increased physician awareness of the current epidemiology of TB and better use of available diagnostic tools will reduce delays and may reduce TB transmission.


An organogel library for solution NMR analysis of nanoparticle suspensions in non-aqueous samples.
Surface contrast solution NMR methods (scNMR) are emerging as powerful tools to investigate the adsorption of small molecule ligands to the surface of nanoparticles (NP), returning fundamental insight into the kinetics and thermodynamics of sorption, as well as structural information on the adsorbed species. A prerequisite for the acquisition of high quality solution NMR data is the preparation of homogeneous and stable samples that return consistent NMR spectra and allow extensive signal averaging. Unfortunately, this condition does not apply to NMR samples containing NPs that often show a tendency to sediment and accumulate at the bottom of the NMR tube over the course of the experiment. We have recently shown that preparing NMR samples in an agarose gel matrix inhibits sedimentation and allows the characterization of small molecule-NP interactions by scNMR. Unfortunately, as the agarose gel only forms in aqueous solution, this sample preparation method cannot be used to stabilize NP suspensions in a non-aqueous environment. Here, we introduce a library of 48 organogels, based on low molecular-mass organic gelators (LMOGs), to prepare NMR samples of small molecule/NP systems in a wide range of organic solvents. In addition, we present a simple method that takes advantage of 1H transverse relaxation (1H-R2) measurements to screen the library and identify the best gelator to characterize the small molecule-NP interaction of interest in the solvent of choice. We expect the results of this study will enable the preparation of homogeneous and stable samples of NPs in non-aqueous environments, therefore dramatically increasing the applicability of scNMR to the characterization of heterogeneous interactions and to the investigation of the role played by solvent molecules in regulating the kinetics and thermodynamics of sorption.


The student's perception of his creativity.
When 590 students at the New York State University of Plattsburgh--both nursing and nonnursing students--were questioned regarding their perceptions of their creativity, nursing students perceived themselves as significantly (p less than .05) less creative.


Toilet training of healthy young toddlers: a randomized trial between a daytime wetting alarm and timed potty training.
Toilet training (TT) is important for every child, but there is no agreement on what is the best training method. We evaluated in a randomized way the comprehensive use of a daytime wetting alarm at home for 5 days in healthy children and compared it with timed potty training. Thirty-nine children, between 20 and 36 months of age, were randomized to wetting alarm diaper training (WAD-T; n = 20) or timed potty training (TP-T; n = 19). Toilet behavior was observed by parents and independent observers before, at the end, and after 2 weeks of training. Late evaluation at 1 month was done by telephone. The WAD-T group did significantly better than the TP-T group at the end training (p = .041), at 14 days (p = .027), and 1 month after training (p = .027). Independent bladder control was achieved in 88.9% of the WAD-T group. The WAD-T method is a structured, child-friendly, highly effective option for TT young healthy children. It offers the parents clear guidelines, a limited time needed to complete TT, a high success rate, and minor emotional conflicts. Results must now be confirmed in a larger sample size.


Psychiatric comorbidities among people with epilepsy: A population-based assessment in disadvantaged communities.
Psychiatric disorders are frequent among people with epilepsy but often under-recognized. The diagnosis and treatment of these disorders in low- and low-middle-income countries (LMICs) are challenging. This cross-sectional survey included people recruited during a community epilepsy screening program involving 59,509 individuals from poor communities in Ludhiana in Northwest India. Adults (age ≥18 years) with confirmed epilepsy on antiseizure medications were screened for depression and anxiety using the Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) and Generalized Anxiety Disorder-7 (GAD-7) twice over two years of follow-up. They were later interviewed for symptoms using the Brief Psychiatric Rating Scale, which was then confirmed by assessments by an experienced psychiatrist. Of the 240 people with confirmed epilepsy, 167 (70%) were adults, of whom, 116 (70%) eventually participated in the study. The NDDI-E with a cut-off of 15 identified depression in 14 (12%) of 116 people after one year of follow-up and 17 (15%) at two years. The GAD-7 using a cut-off of 6 identified 22 (19%) at one year and 32 (28%) with anxiety at two years. The area under the curves for NDDI-E was estimated as 0.62 (95%CI, 0.51-0.73; SE: 0.06; p = 0.04) and for GAD-7 as 0.62 (95%CI, 0.46-0.78; SE: 0.08; p = 0.12). Brief Psychiatric Rating Scale identified 63 (54%) people with psychiatric symptoms, for whom, a psychiatric diagnosis was confirmed in 60 (52%). A psychiatric diagnosis was associated with education below high school [Odds Ratio (OR): 2.59, 95%CI, 1.12-5.1; p = 0.03], later age of seizure onset (OR, 1.05, 95%CI: 1.0-1.10; p = 0.04), seizure frequency of at least one/year at enrolment (OR, 2.36, 95%CI: 1.0-5.58; p = 0.05) and the use of clobazam (OR, 5.09, 95%CI, 1.40-18.42; p = 0.01). Depression and anxiety are common in people with epilepsy. Our findings underscore the low yields of screening instruments, NDDI-E and GAD-7, and comparatively better professionally-administered diagnostic assessments in resource-limited settings in LMICs. Moreover, previously established cut-offs do not apply to the community studied.


Self-Assembled Nanoparticles with E Protein Domains I and II of Duck Tembusu Virus Can Induce a More Comprehensive Immune Response Against the Duck Tembusu Virus Challenge.
Duck Tembusu virus (DTMUV) is a pathogenic flavivirus that causes a substantial drop in egg production and severe neurological disorders in domestic waterfowl. Self-assembled ferritin nanoparticles with E protein domains I and II (EDI-II) of DTMUV (EDI-II-RFNp) were prepared, and its morphology was observed. Two independent experiments were conducted. First, Cherry Valley ducks aged 14 days were vaccinated with EDI-II-RFNp, EDI-II, and phosphate buffered solution (PBS, pH 7.4), and special and virus neutralization (VN) antibodies, interleukin 4 (IL-4) and interferon gamma (IFN-γ) in serum, and lymphocyte proliferation were detected. Second, the vaccinated ducks with EDI-II-RFNp, EDI-II, and PBS were injected with virulent DTMUV, clinical signs at 7 days postinfection (dpi) were observed, and mRNA levels of DTMUV in the lungs, liver, and brain at 7 and 14 dpi were detected. The results showed near-spherical nanoparticles EDI-II-RFNp with a 16.46 ± 4.70 nm diameters. The levels of specific and VN antibodies, IL-4 and IFN-γ, and lymphocyte proliferation in the EDI-II-RFNp group were significantly higher than those in the EDI-II and PBS groups. In the DTMUV challenge test, clinical signs and mRNA levels in tissue were used to evaluate protection of EDI-II-RFNp. EDI-II-RFNp-vaccinated ducks showed milder clinical signs and lower levels of DTMUV RNA in the lungs, liver, and brain. These results indicate that EDI-II-RFNp effectively protects ducks against the DTMUV challenge and could be a vaccine candidate to provide an effective and safe method for preventing and controlling DTMUV infection.


Nanotechnology in the COVID-19 era: Carbon-based nanomaterials as a promising solution.
The Coronavirus Disease 2019 (COVID-19) pandemic has led to collaboration between nanotechnology scientists, industry stakeholders, and clinicians to develop solutions for diagnostics, prevention, and treatment of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections. Nanomaterials, including carbon-based materials (CBM) such as graphene and carbon nanotubes, have been studied for their potential in viral research. CBM unique effects on microorganisms, immune interaction, and sensitivity in diagnostics have made them a promising subject of SARS-CoV-2 research. This review discusses the interaction of CBM with SARS-CoV-2 and their applicability, including CBM physical and chemical properties, the known interactions between CBM and viral components, and the proposed prevention, treatment, and diagnostics uses.


Altered centromedial amygdala functional connectivity in adults is associated with childhood emotional abuse and predicts levels of depression and anxiety.
Childhood maltreatment is significantly associated with greater occurrence of mental disorders in adulthood such as depression and anxiety. As a key node of the limbic system, the amygdala is engaged in emotional processing and regulation and is dysfunctional in many psychiatric disorders. The present study aimed at exploring the association between childhood maltreatment and amygdala-based functional networks and their potential contributions to depression and anxiety. Totally 90 Chinese healthy volunteers participated in a resting-state fMRI experiment. Levels of childhood maltreatment experience were assessed using the Childhood Trauma Questionnaire (CTQ-SF) as well as levels of depression and anxiety. Associations between CTQ-SF scores and bilateral amygdala gray matter volume and resting-state functional connectivity (RSFC) of the amygdala and selected regions of interest were analyzed using multiple regression analyses with sex and age as covariates. A subsequent moderation analysis was performed to identify whether associations were predictive of depression and anxiety levels. Childhood maltreatment was significantly negatively associated with RSFC between left amygdala and anterior insula. Further sub-region analyses revealed that this negative association only occurred for the left centromedial amygdala subregion, which subsequently moderated the relationship between levels of childhood emotional abuse and depression / anxiety. No psychiatric patients were involved and specific neural associations with different childhood maltreatment subtypes need to be examined in future studies. The present findings provide evidence for altered RSFC of centromedial amygdala and the anterior insula associated with childhood maltreatment and which moderate levels of depression and anxiety in adulthood.


Effects of chronic manipulation of adrenocorticotropic hormone levels in Chinook salmon on expression of interrenal steroidogenic acute regulatory protein and steroidogenic enzymes.
The effects of chronic exposure to adrenocorticotropic hormone (ACTH) or the synthetic glucocorticoid dexamethasone (DEX) on the expression of genes involved in cortisol synthesis were examined using quantitative RT-PCR and immunohistochemistry. Juvenile Chinook salmon were treated with either ACTH via micro-osmotic pumps or with DEX via a lipid-based sustained release vehicle. Plasma cortisol levels were significantly elevated in ACTH-treated fish after 1 day, with a significant reduction in this effect with increasing treatment duration. ACTH also appeared to cause progressive hyperplasia of interrenal cells. Steroidogenic acute regulatory protein (StAR) and cytochrome P450 side chain cleavage enzyme (P450scc) transcripts but not 3β-hydroxysteroid dehydrogenase-isomerase (3β-HSD) or cytochrome P450 11β-hydroxylase (P45011β) transcripts in head kidneys significantly increased after 5 days of ACTH treatment. Significant linear relationships between plasma cortisol levels and transcript levels were identified at day 1 and day 5 for StAR, and day 5 for P450scc. Increased immunoreactivity for P450scc was observed in interrenal cells of ACTH-treated fish after 5 and 10 days. No effect of ACTH on 3β-HSD immunoreactivity was apparent at any time point. P45011β immunoreactivity was more intense after 5 days treatment with ACTH. DEX significantly reduced resting plasma cortisol levels and induced interrenal cell atrophy. Although no significant effect of treatment with DEX was found for any transcript, immunoreactivity for P450scc and P45011β appeared to be reduced. These results indicate that StAR and P450scc are subject to transcriptional regulation by chronic changes in ACTH levels.


Global and peak local specific absorption rate control on parallel transmit systems using k-means SAR compression model.
To improve the specific absorption rate (SAR) compression model capability in parallel transmission (pTx) MRI systems. A k-means clustering method is proposed to group voxels with similar SAR behaviors in the scanned object, providing a controlled upper-bounded estimation of peak local SARs. This k-means compression model and the conventional virtual observation point (VOP) model were tested in a pTx MRI framework. The pTx pulse design with different SAR controlling schemes was simulated using a numerical human head model and an eight-channel 7T coil array. Multiple criteria (including RF power, global and peak local SARs, and excitation accuracy) were compared for the performance testing. The k-means compression model generated a narrower overestimation bound, leading to a more accurate local SAR estimation. Among different pTx pulse design approaches, the k-means compression model showed the best trade-off between the SAR and excitation accuracy. The developed SAR compression model is advantageous for pTx framework given the narrower overestimation bound and control over the compression ratio. Results also illustrate that a moderate increase of maximum RF power can be useful for reducing the maximum local SAR deposition.


Vascular endothelial growth factor 1498C/T, 936C/T polymorphisms associated with increased risk of colorectal adenoma: a Chinese case-control study.
Single nucleotide polymorphisms in vascular endothelial growth factor gene VEGF, 1498C/T and 936 C/T are associated with colorectal cancer. We sought to determine whether such genetic variability in VEGF contributes to susceptibility of colorectal adenoma (CRA), a presumably precancerous state of colorectal cancer. In this research, two aforementioned polymorphisms were investigated for CRA susceptibility in a Chinese case-control study. The epidemiological risk factors were collected through questionnaire. The plasma VEGF levels were measured via enzyme-linked immunosorbent assay (ELISA). The Taqman-Probe assay was used to determine genotypes in 224 CRA patients and 200 CRA-free controls. The clinicopathological data of each sample were collected for further correlation analysis. According to data analysis males, cigarette smokers, patients who carry metabolic syndrome or familial antecedent of adenomas were significantly associated with CRA risk. Plasma VEGF levels of CRA patients were higher than those of controls (P = 0.003). This difference is independent of genotypes. The carriers with 936CT and CT+TT had higher risk of CRA in comparison with controls (CT vs. CC, OR 2.00, 95% CI 1.23-3.25, P = 0.006; CT+TT vs. CC, OR 2.04, 95% CI 1.28-3.26, P = 0.003). 936-T allele was associated with increased risk of CRA (OR 1.91, 95% CI 1.25-2.91, P = 0.003). Both CRA and control show no difference in the genotype of 1498C/T and the allele frequency of C-/T-. CRA patients with haplotype 1498T+936T presented significantly higher risk than those with wild-type 1498T+936C. Moreover, patients carrying 936CT+TT and 936-T allele demonstrated a tendency for villous adenoma. CRA patients have elevated plasma VEGF levels. The VEGF 936C/T polymorphism and 1498T+936T haplotype were found to be associated with increased CRA susceptibility.


Cecal intubation model in the rat that facilitates selective in vivo study of colonic epithelial biology: preliminary report.
A free-living animal model with ready and repetitive access to selected regions of the large bowel and with minimally altered bowel anatomy and physiology would facilitate the in vivo study of luminal factors on the colonic mucosa in a steady-state environment. This study describes a novel model of large-bowel intubation in the rat. Four Sprague-Dawley rats (240-260 g) had laparotomy and intubation of the distal colon and the cecum via a cecotomy with the use of two small tubes with restraints and transmural anchors. The tubes were tunneled and anchored to the back for infusion of fluid directly into the colon. Tube positions were studied when the animals were killed. Animals were fed on either a 10 percent fiber diet or a fiber-free diet. Stathmokinetic assessment of the distal colon was performed after one week of infusion with phosphate-buffered saline and sodium n-butyrate. The technique produced an easy access without affecting the weight gain of the animals after recovery. Tube positions were accurate after three weeks at the time the animals were killed. Infusions of phosphate-buffered saline and n-butyrate were well tolerated. n-Butyrate infusions twice daily for a week reversed the atrophy in the colonic mucosa induced by dietary fiber deprivation. An in vivo large-bowel intubation model permitting selective delivery of luminal factors provides an effective option for the study of colonic mucosal biology.


[The role of the micrographic surgery in the management of basal cell carcinoma: experience in the Department of Dermatology, at the Hassan II University Hospital, Fes, Morocco].
Mohs micrographic surgery (MMS) is a technique allowing for intraoperative histologic assessment of surgical margin of malignant tumors. This study aims to highlight the role of MMS in the achievement of radical healing of basal cell carcinoma (BCC) in our patients. We conducted a study of 29 patients with basal cell carcinoma of the face over a period of 5 years. The median age of patients was 45.8 years (12-80). The sex-ratio M/F was 1.23. One-stage surgical procedure was sufficient to obtain complete resection in 51% of cases. Three-stage surgical procedure was needed in 14% of the cases. The mean duration of one-stage surgical procedure was 1 hour. No complications were reported in the postoperative period and sequelae were simple. The aesthetic and functional result was satisfactory. No recurrence was noted. BCC accounts for approximately 80% of all skin cancers. The decision to use MMS to treat BCC is based on three variables: the seat and the size of the tumor, its histological appearance with the identification of resection margin and its recurrent nature. MMS is currently the most effective method in the treatment of BCC and allows maximum healthy tissue preservation. It is a safe and repeatable surgical procedure based on team work and adapted to the treatment of patients with BCC who are at high risk of recidivism. The aesthetic and functional results are satisfactory. Recurrence rate at 5 years is 10 times lower than with the other methods.


Hemorrhage in the endolymphatic sac: a cause of hearing fluctuation in enlarged vestibular aqueduct.
Most of the patients with enlarged vestibular aqueduct (EVA) experience sudden hearing deterioration, but the exact mechanism is unclear. We analyzed magnetic resonance (MR) images and the cellular components of endolymph obtained from the endolymphatic sac in patients with EVA, in order to demonstrate the cause of sudden hearing loss. A total of 25 patients (50 ears) with EVA, who had severe to profound hearing loss, were included in this retrospective clinical study. MR examinations were performed by a 3.0-T MR system using an 8-channel sensitivity-encoding head coil. We analyzed endolymphatic fluid harvested from the endolymphatic sac during cochlear implantations in four patients. The area of low signal intensity in the endolymphatic sac was observed on T2-weighted MR images for 15 of 50 ears. This area was observed more frequently in patients who experienced recent sudden hearing loss (10/12, 83%) than those with stable hearing (5/38, 13%)(Fisher's exact test, p<0.001). In addition, this area showed high signal intensity on fluid attenuated inversion recovery images. Cytologic analysis of the aspirated endolymph from the endolymphatic sac in the patients with this area revealed many erythrocytes. Our data suggests that hemorrhage in the endolymphatic sac could be a cause of sudden hearing deterioration in patients with EVA.


[Endocanalicular dacryocystorhinostomy (E-DCR): relevance of materials standardization for outcomes].
After 5 years' experience with endocanalicular dacryocystorhinostomy (E-DCR) using diode laser, the introduction of new materials has led to significant technical differences, thus giving rise to this study to evaluate them. We compare the behaviour of 2 different kinds of laser guide fibre (silica-fluoropolymer-tefzel and silica-silica-polyamide), using the same laser generator, on organic tissues from fresh animal carcases, and we summarize the clinical behaviour of the new materials in lachrymal surgery cases. We have seen significant differences in the clinical behaviour of the two kinds of laser guides, namely the proposed new materials have a worse behaviour on organic tissues than their physical characteristics might theoretically have suggested. Thus, the use of different guide materials could lead to relevant differences in terms of surgical results, as well as in the comparison of the outcomes of series performed by different surgeons. It is necessary to determine standards for the materials recommended for this surgery, not only for easier technical performance and better effectiveness, but also to allow comparison of results from different authors.


Assignment of the human TIM proto-oncogene to 7q33-->q35.
The human transforming gene TIM has been mapped to human chromosome 7 region q33-->q35 by fluorescence in situ hybridization with R-banded chromosomes. Rearrangements within this region have been reported to occur in acute myeloid leukemia cells.


Diabetic retinopathy detection using red lesion localization and convolutional neural networks.
Detecting the early signs of diabetic retinopathy (DR) is essential, as timely treatment might reduce or even prevent vision loss. Moreover, automatically localizing the regions of the retinal image that might contain lesions can favorably assist specialists in the task of detection. In this study, we designed a lesion localization model using a deep network patch-based approach. Our goal was to reduce the complexity of the model while improving its performance. For this purpose, we designed an efficient procedure (including two convolutional neural network models) for selecting the training patches, such that the challenging examples would be given special attention during the training process. Using the labeling of the region, a DR decision can be given to the initial image, without the need for special training. The model is trained on the Standard Diabetic Retinopathy Database, Calibration Level 1 (DIARETDB1) database and is tested on several databases (including Messidor) without any further adaptation. It reaches an area under the receiver operating characteristic curve of 0.912-95%CI(0.897-0.928) for DR screening, and a sensitivity of 0.940-95%CI(0.921-0.959). These values are competitive with other state-of-the-art approaches.


[Serum autoantibodies against the cardiac beta(1)-adrenergic receptor in patients with chronic heart failure: clinical characteristics and response to carvedilol].
To detect the serum autoantibodies against the cardiac beta(1)-adrenergic receptor and observe the clinical characteristics and response to carvedilol use in patients with chronic heart failure (CHF). Cardiac function was examined by echocardiography and levels of autoantibodies against cardiac beta(1)-adrenergic receptor were detected in 65 patients with CHF by means of enzyme linked immune assay. Carvedilol was added on ACEI, diuretics and digitalis regimen for a target dose of 50 mg/d. All patients were followed up for 6 months. Autoantibodies against cardiac beta(1)-adrenergic receptor were detected in 30 patients (group 1) and not detected in the remaining 35 patients (group 2). The achieved target dose of carvedilol was significantly higher in group 1 than that in group 2 [(36.25 +/- 14.31) mg/d vs. (25.97 +/- 8.83) mg/d, P < 0.01]. Heart rate was significantly higher in group 1 compared to group 2 [(94.19 +/- 14.46) beats/min vs. (86.56 +/- 15.88) beats/min, P < 0.05] before treatment and heart rate and blood pressure of both groups decreased significantly (P < 0.01) and there was no significant difference between two group (P > 0.05) after 6 months treatment. LVEDD and LVESD were significantly larger while LVEF significantly lower in group 1 patients than those in group 2 patients (all P < 0.05) before treatment and LVEDD and LVESD decreased and LVEF increased significantly in both groups (all P < 0.01 vs. before treatment) and there was on significant difference in LVEDD, LVESD and LVEF between two groups (all P > 0.05) post 6 months treatment. Moreover, average titer of autoantibodies against the cardiac beta(1)-adrenergic receptors significantly decreased after 6 months treatment (1:119.35 vs. 1:72.21, P < 0.01). The detection of autoantibodies against the cardiac beta(1)-adrenergic receptors is related to severer cardiac dysfunction and autoantibodies title decrease was found with improved cardiac function after standard therapy (ACEI, digitalis, betablocker) in patients with CHF.


Late components of saccade-related brain potentials in guessing tasks.
The late positive components of lambda responses were studied in a guessing task modified in such a way that subjects had to perform a saccadic eye movement in order to perceive task-relevant information. Responses from 6 scalp areas were investigated in 9 subjects and in 2 conditions: control and guessing. In both conditions subjects performed two consecutive saccades in a given trial: the first to the middle light, the second to the target area. In the control condition the subjects knew beforehand what the 'target' would be. In the guessing condition they had to make a guess before each trial as to which of the three target stimuli would appear. The target stimuli occurred with unequal probability and were presented in a randomized sequence. Unlike the control condition, the guessing task led to the appearance of a late positive component in the lambda response. Similar to traditional ERP findings, this late positivity showed an amplitude maximum at the parietal area and a peak latency at 375 msec from saccade onset. Furthermore, Principal Component-Varimax Analysis (PCVA) of the lambda responses revealed a first factor giving the strongest loading in the latency range of the P300, and a second factor which was identified as the slow wave. These factors are quite similar to the factors found in the PCVA of ERPs. Our results suggest that the late components of lambda responses reflect the effects of information processing in cognitive tasks similarly to the way the late positive components of ERPs do.


Hyperintense basal ganglia on T1-weighted magnetic resonance images in a patient with common variable immunodeficiency associated with elevated serum manganese.
The authors report on a 32-year-old man with common variable immunodeficiency and high signal intensity in basal ganglia on T1-weighted images. No signal alteration on T2-weighted and postcontrast images was observed. The patient had elevated levels of manganese in the serum. The authors conclude that the unusual hyperintensity in the basal ganglia area on T1-weighted images resulted from manganese deposition due to liver dysfunction.


Identification of potential targets of cinnamon for treatment against Alzheimer's disease-related GABAergic synaptic dysfunction using network pharmacology.
Cinnamon aqueous extract's active substance base remains unclear and its mechanisms, mainly the therapeutic target of anti-Alzheimer's disease (AD)-related GABAergic synaptic dysfunction, remain unclear. Here, 30 chemical components were identified in the aqueous extract of cinnamon using LC/MS; secondly, we explored the brain-targeting components of the aqueous extract of cinnamon, and 17 components had a good absorption due to the blood-brain barrier (BBB) limitation; thirdly, further clustering analysis of active ingredient targets by network pharmacology showed that the GABA pathway with GABRG2 as the core target was significantly enriched; then, we used prominent protein-protein interactions (PPI), relying on a protein-metabolite network, and identified the GABRA1, GABRB2 and GABRA5 as the closest targets to GABRG2; finally, the affinity between the target and its cognate active compound was predicted by molecular docking. In general, we screened five components, methyl cinnamate, propyl cinnamate, ( +)-procyanidin B2, procyanidin B1, and myristicin as the brain synapse-targeting active substances of cinnamon using a systematic strategy, and identified GABRA1, GABRB2, GABRA5 and GABRG2 as core therapeutic targets of cinnamon against Alzheimer's disease-related GABAergic synaptic dysfunction. Exploring the mechanism of cinnamon' activities through multi-components and multiple targets strategies promise to reduce the threat of single- target and symptom-based drug discovery failure.


S-1 monotherapy as second- or third-line chemotherapy for unresectable and recurrent esophageal squamous cell carcinoma.
S-1 is widely used for various cancers. It may be useful for esophageal squamous cell carcinoma (ESCC); however, there are insufficient data. The purpose is to provide results of an analysis of S-1 monotherapy for unresectable and recurrent ESCC. Twenty patients with histologically proven ESCC who were previously treated with other chemo(radio)therapies were treated with S-1 alone as second- or third-line chemotherapy. A complete response (CR) was observed in 1 case (5%). A partial response (PR), stable disease (SD), and progressive disease (PD) were seen in 4 (20.0%), 7 (35.0%), and 8 (40.0%) cases, respectively. Two cases (10%) of anemia, 1 case (5%) of leukopenia, 3 cases (15%) of fatigue, and 3 cases (15%) of diarrhea were observed as grade 3 toxicity; however, there were no cases of grade 4 toxicity. The 1-year progression-free survival (PFS) rate was 10.0%, and the median PFS was 100 days. The 1-year overall survival (OS) was 30.5%, and the median OS was 330 days. The 1-year PFS rate in CR/PR/SD and PD was 16.7 and 0%, and the median survival time was 120 and 40 days. S-1 is a promising new drug which can be used as a second- or third-line chemotherapy for ESCC.


Changes in detrusor muscle oxygenation during detrusor overactivity contractions.
To investigate changes in the oxygenated and deoxygenated haemoglobin (Hb) of the bladder wall during voluntary and involuntary detrusor contractions. Women with lower urinary tract symptoms were recruited from a urodynamics clinic. Near infra-red spectroscopy, a non-invasive optical technique which monitors changes in tissue oxygenation, was used to measure oxygenated and deoxygenated haemoglobin simultaneously while the women underwent urodynamics. All data were compared using paired sample t-test. Fifty-five women with a mean age of 52 years were enrolled into the study. In the 23 women with detrusor overactivity (15 with isolated detrusor overactivity and 8 with mixed urinary incontinence) there was a statistically significant rise in deoxygenated Hb during involuntary detrusor contractions at maximum detrusor pressure compared to the start of filling (p=0.02). There was no statistically significant change between Hb parameters measured at the start of the filling phase and those measured during voluntary detrusor contraction at pdetQmax (detrusor pressure at maximum flow rate). The mean detrusor pressure measured during voiding, however, was significantly higher than the maximum pressure during involuntary detrusor contractions (p=0.03). There is a significant rise in the deoxygenated Hb in the detrusor muscle during detrusor overactivity, which is not seen during voiding even when the pdetQmax was higher than the peak detrusor pressure during involuntary contractions. These interesting changes in detrusor muscle oxygenation during involuntary detrusor contraction need to be explored further to assess if deoxygenation plays a role in the pathogenesis of detrusor overactivity.


Cytotoxic effect of efavirenz is selective against cancer cells and associated with the cannabinoid system.
Recently, a regression of precancerous lesions in HIV-1-infected patients after initiation of HAART was reported. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) as efavirenz (EFV) might be mediators of this effect, as they are known to have a cytotoxic effect on tumour cells. A potential mechanism involved in this effect may be the activation of the cannabinoid receptor to mediate tumour toxicity. Several tumour-derived and fibroblast cell lines were studied. Cytotoxicity of EFV was evaluated by Annexin-Pi staining. The expression of the cannabinoid receptors CB1, CB2 and GPR55 was analysed by western blot, quantitative reverse transcriptase (qRT-PCR) and fluorescence activated cell sorting. The influence of the cannabinoid agonists and antagonists on the effects of EFV was investigated. Furthermore, the effect of EFV on the phosphorylation state of the growth factors Erk, Akt and the tumour suppressor protein p53 was tested. EFV revealed a selective cytotoxic effect on several tumour cell lines, whereas primary fibroblasts were not affected. The cytotoxic effect was associated with the expression of CB1. The combination of EFV with cannabinoid agonists showed an increase in toxicity. The phosphorylation state of Erk and Akt was not affected by EFV, whereas p53 showed an increased phosphorylation. EFV has a selective cytotoxic effect on several tumour cells. Furthermore, EFV led to an activating phosphorylation of the tumour suppressor protein p53 going in line with earlier reports that EFV may be antitumourigenic and a potential cytostatic drug. The observed synergistic effect with cannabinoid agonists implicates an involvement of the cannabinoid system.


The integrative care conference: an innovative model for teaching at the heart of communication in medicine.
By focusing on the biomedical aspects of a disease, physicians often dismiss the emotional effect that patients have on them and the stories that provide meaning to the patients' experience with illness. This approach often leads to strained relationships, medical errors, and dehumanized health care. We describe the Integrative Care Conference, an interdisciplinary format for teaching enhanced communication between residents and their patients. Three findings emerged: (a) The gap between what the resident knows about the patient and what is relevant to the patient's health care is wide. (b) Despite this gap, patients express great appreciation for their physician. (c) After learning about their patients' life and relationships, residents developed more humanistic approaches to their patient that reshaped treatment. The Integrative Care Conference provides a powerful format for teaching patient-physician communication.


Determining the number of independent sources of the EEG: a simulation study on information criteria.
The separation of signal and noise is an important problem in the analysis of EEG and MEG data. Furthermore, many source localisation strategies need the number of independent signal components as input parameter (e.g., dipole fit, multiple signal classification). Information criteria offer a relatively objective way to separate the space spanned by the principal components of the data covariance matrix into a signal and a noise part. Eighteen such criteria were extensively tested by simulations. They differ with respect to the statistical model of the data, the assumptions on the noise, and the correction term. In the simulations, different dipole sources were used to generate EEG, which was then distorted by Gaussian correlated or uncorrelated noise. The noise level, the accuracy of the noise covariance matrix used by the criteria, the numbers of channels and time samples, and the stochastic or deterministic nature of the source waveforms were varied. The performance of the criteria was very variable. For each criterion, limits for the noise level and the relative inaccuracy of the noise covariance matrix could be established. Taking more channels or time steps did increase the criteria's ability to tolerate noise, but at the same time, made them more vulnerable to inaccuracies in the (estimated) noise covariance matrices. Out of the eighteen criteria investigated, we recommend two criteria that are best suited for the cases of (1) high noise and accurate covariances and (2) low noise and less accurate covariances.


Clinical applications of the auditory brain stem response.
The auditory brain stem response is a powerful new tool for the detection and quantification of hearing impairment, especially in the pediatric population. It gives exact information about the functional status of the cochlea and brain stem pathways. The technique distinguishes recruiting from nonrecruiting losses, predominantly high frequency from flat losses, and retrocochlear from peripheral disorders. The recent introduction of bone conducted stimuli should soon permit the unambiguous separation of conductive and sensorineural losses.


Potential role of N-myristoyltransferase in cancer.
Colorectal cancer is the second leading cause of malignant death, and better preventive strategies are needed. The treatment of colonic cancer remains difficult because of the lack of effective chemotherapeutic agents; therefore it is important to continue to search for cellular functions that can be disrupted by chemotherapeutic drugs resulting in the inhibition of the development and progression of cancer. The current knowledge of the modification of proteins by myristoylation involving myristoyl-CoA: protein N-myristoyltransferase (NMT) is in its infancy. This process is involved in the pathogenesis of cancer. We have reported for the first time that NMT activity and protein expression were higher in human colorectal cancer, gallbladder carcinoma and brain tumors. In addition, an increase in NMT activity appeared at an early stage in colonic carcinogenesis. It is conceivable therefore that NMT can be used as a potential marker for the early detection of cancer. These observations lead to the possibility of developing NMT specific inhibitors, which may be therapeutically useful. We proposed that HSC70 and/or enolase could be used as an anticancer therapeutic target. This review summarized the status of NMT in cancer which has been carried in our laboratory.


[Morphological analysis of the hippocampal region associated with an innate behaviour task in the transgenic mouse model (3xTg-AD) for Alzheimer disease].
Different animal models for Alzheimer disease (AD) have been designed to support the hypothesis that the neurodegeneration (loss of neurons and synapses with reactive gliosis) associated with Aβ and tau deposition in these models is similar to that in the human brain. These alterations produce functional changes beginning with decreased ability to carry out daily and social life activities, memory loss, and neuropsychiatric disorders in general. Neuronal alteration plays an important role in early stages of the disease, especially in the CA1 area of hippocampus in both human and animal models. Two groups (WT and 3xTg-AD) of 11-month-old female mice were used in a behavioural analysis (nest building) and a morphometric analysis of the CA1 region of the dorsal hippocampus. The 3xTg-AD mice showed a 50% reduction in nest quality associated with a significant increase in damaged neurons in the CA1 hippocampal area (26%±6%, P<.05) compared to the WT group. The decreased ability to carry out activities of daily living (humans) or nest building (3xTg-AD mice) is related to the neuronal alterations observed in AD. These alterations are controlled by the hippocampus. Post-mortem analyses of the human hippocampus, and the CA1 region in 3xTg-AD mice, show that these areas are associated with alterations in the deposition of Aβ and tau proteins, which start accumulating in the early stages of AD.


Grid cells require excitatory drive from the hippocampus.
To determine how hippocampal backprojections influence spatially periodic firing in grid cells, we recorded neural activity in the medial entorhinal cortex (MEC) of rats after temporary inactivation of the hippocampus. We report two major changes in entorhinal grid cells. First, hippocampal inactivation gradually and selectively extinguished the grid pattern. Second, the same grid cells that lost their grid fields acquired substantial tuning to the direction of the rat's head. This transition in firing properties was contingent on a drop in the average firing rate of the grid cells and could be replicated by the removal of an external excitatory drive in an attractor network model in which grid structure emerges by velocity-dependent translation of activity across a network with inhibitory connections. These results point to excitatory drive from the hippocampus, and possibly other regions, as one prerequisite for the formation and translocation of grid patterns in the MEC.


The coccoid forms of Helicobacter pylori. Criteria for their viability.
The fact that Helicobacter pylori can revert to a coccoid form has stimulated speculation about its role in transmission and as a possible cause of reinfection in duodenal ulcer disease. Bismuth subcitrate (32 micrograms/ml), bismuth subsalicylate (64 micrograms/ml), amoxicillin (0.05 micrograms/ml) and erythromycin (4 micrograms/ml) inhibited the growth of H. pylori and stimulated the formation of basically respiring but non-culturable coccoid structures. The presence of polyphosphates as energy and phosphorus source permits a certain level of endogenous metabolism to preserve RNA and DNA, as well as structural components like cell wall, cell membrane and cytoplasma for at least 3 months. However, the applied standard laboratory methods were insufficient for regrowth of H. pylori out of the coccoid form.


Effects of felodipine and metoprolol on blood pressure, plasma renin, angiotensin II, aldosterone and catecholamines in hypertensive patients.
Oral administration of felodipine to 10 patients with mild essential hypertension acutely reduced the brachial artery pressure by 15/13mm Hg. The tachycardia which occurred was sustained for 90 minutes together with an elevated plasma noradrenaline concentration. Addition of intravascular metoprolol after 90 minutes decreased heart rate. The felodipine-induced increase of plasma renin activity (100%; p less than 0.001) was completely reversed by metoprolol. Plasma angiotensin II (PA II) rose by 15% (p less than 0.05) during felodipine, whereas plasma aldosterone concentration was not significantly affected.


Familial differences in the effects of mercury on reproduction in zebra finches.
Ecotoxicologists often implicitly assume that populations are homogenous entities in which all individuals have similar responses to a contaminant. However, genetically variable responses occur within populations. This variation can be visualized using dose-response curves of genetically related groups, similar to the way that evolutionary biologists construct reaction norms. We assessed the variation in reproductive success of full-sibling families of captive zebra finches (Taeniopygia guttata) experimentally exposed to methylmercury. We found significant variation among families in the effects of methylmercury on several reproductive parameters. This variation suggests that there may be strong responses to selection for resistant genotypes in contaminated areas. This has important implications for the evolution of tolerance as well as risk assessment and wildlife conservation efforts on sites with legacy contamination.


Preliminary field study of hepatic porphyrin profiles of Astyanax fasciatus (Teleostei, Characiformes) to define anthropogenic pollution.
The implementation of eco-toxicological assessment in South America is presently limited due to significant scientific information gaps concerning native species and their potential use as biomarkers. Recently, a common southern hemisphere fish species, Astyanax fasciatus, has been pointed out as a potential bio-indicator to anthropogenic pollution. This is a small, abundant, Neotropical characid, which is widely distributed from Central America south, to the Rio de la Plata Basin of western Uruguay. Our study found a statistically significant increase of coproporphyrin, uroporphyrin and protoporphyrin concentrations in hepatic tissues of A. fasciatus collected from a stream segment with high anthropogenic disturbance (due mainly to agricultural derivatives and motor vehicle transportation activities). Although the area studied showed differences in up and downstream limno-chemical parameters, these differences were not related to the increase of hepatic porphyrin concentrations. Based on the results of our study, we conclude that A. fasciatus is a good bio-indicator of exposure to environmental contaminants, and we propose that this abundant fish species be considered as a sentinel organism for monitoring potential disturbances to freshwater ecosystems.


Investigation of drought induced biochemical and gene expression changes in carrot cultivars.
Carrot is the most important vegetable in Apiaceae family, and it is consumed globally due to its high nutritional quality. Drought stress is major environmental constraint for vegetables especially carrot. Limited data is available regarding the mechanisms conferring drought tolerance in carrot. Methods and Results Eight commercial carrot cultivars were used in this study and subjected to drought stress under semi-controlled greenhouse conditions. Biochemical, antioxidant enzymatic activity and changes in transcript level of drought related genes was estimated, the gene expression analysis was done by using qRT-PCR in comparison with reference gene expression Actin (Act1). Results revealed that cultivars Coral Orange, Tendersweet and Solar Yellow were tolerant to drought stress, which was supported by their higher transcript levels of catalase gene (CAT), superoxide dismutase genes (Cu/ZN-SOD, Cu/Zn-SDC) in these cultivars. The downregulation of PDH1 gene (Proline dehydrogenase 1) was also observed that was associated with upregulation of proline accumulation in carrot plants. Moreover, results also suggested that PRT genes (Proline transporter genes) played a key role in drought tolerance in carrot cultivars. Conclusion Among the cultivars studied, Coral Orange showed overall tolerance to drought stress conditions, whereas cultivars Cosmic Purple and Eregli Black were sensitive based on their biochemical and gene expression levels. According to our knowledge, this is the first comparative study on drought tolerance in several carrot cultivars. It will provide a background for carrot breeding to understand biochemical and molecular responses of carrot plant to drought stress and mechanisms behind it.


mRNA-specific translation regulation by a ribosome-associated ncRNA in Haloferax volcanii.
Regulation of gene expression at the translational level allows rapid adaptation of cellular proteomes to quickly changing environmental conditions and is thus central for prokaryotic organisms. Small non-coding RNAs (sRNAs) have been reported to effectively orchestrate translation control in bacteria and archaea mainly by targeting mRNAs by partial base complementarity. Here we report an unprecedented mechanism how sRNAs are capable of modulating protein biosynthesis in the halophilic archaeon Haloferax volcanii. By analyzing the ribosome-associated ncRNAs (rancRNAs) under different stress conditions we identified an intergenic sRNA, termed rancRNA_s194, that is primarily expressed during exponential growth under all tested conditions. By interaction with the ribosome rancRNA_s194 inhibits peptide bond formation and protein synthesis in vitro but appears to target a specific mRNA in vivo. The respective knock-out strain shows a reduced lag phase in media containing xylose as sole carbon source and outcompetes the wildtype cells under these conditions. Mass spectrometry, polysome profiling and mRNA binding competition experiments suggest that rancRNA_s194 prevents the cstA mRNA from being efficiently translated by H. volcanii ribosomes. These findings enlarge the regulatory repertoire of archaeal sRNAs in modulating post-transcriptional gene expression.


Associations of Gastrointestinal Tract Tumor Necrosis Factor Receptor-Associated Factor 6 Expression with Clinical Features and Prognosis of Eosinophilic Gastroenteritis.
Few studies have been conducted to explore the expression of tumor necrosis factor receptor-associated factor 6 in eosinophilic gastroenteritis patients. Therefore, the expression profile of tumor necrosis factor receptor-associated factor 6 in the gastrointestinal tract of eosinophilic gastroenteritis patients and its associations with clinical features were explored in this study. Thirty-four eosinophilic gastroenteritis patients who presented in Ruijin Hospital from December 2012 to May 2019 and had accepted gastrointestinal endoscopic examinations were recruited. Medical records and endoscopic biopsies were collected, and the prognosis was followed up by telephone. Healthy persons were selected as the control group. Hematoxylin and eosin and immunohistochemical staining were performed in both eosinophilic gastroenteritis patients and healthy persons. The final results were analyzed by skilled pathologists, and mean optical density values of tumor necrosis factor receptor-associated factor 6 were calculated by Image J software. Final results were analyzed by Statistical Package for the Social Sciences software 22.0. Thirty-four patients (mean age: 25.56 ± 21.14 years, 61.76% males) were recruited for this study. There was no significant difference in tumor necrosis factor receptor-associated factor 6 mean optical density values of gastric tissues in eosinophilic gastroenteritis patients and healthy people (0.22 ± 0.16 vs. 0.14 ± 0.05, P > .05). Eosinophilic gastroenteritis patients had a significantly lower level of intestinal tumor necrosis factor receptor-associated factor 6 mean optical density values than that of healthy people (0.16 ± 0.05 vs. 0.23 ± 0.06, P < .05). Intestinal tumor necrosis factor receptor-associated factor 6 mean optical density values negatively linearly correlated with serum interleukin-10 level (r = -0.618, P = .043 < .05). There were no differences between eosinophilic gastroenteritis patients with or without relapse regarding the expression level of intestinal tumor necrosis factor receptor-associated factor 6 (P = .227 > .05). Patients with eosinophilic gastroenteritis might have a deficiency of intestinal tumor necrosis factor receptor-associated factor 6 compared to healthy controls.