Cytosol and nuclear estrogen and progesterone receptors in the rabbit endocervix.
This report describes the measurement of estrogen and progesterone receptors in cytosols and nuclear fractions from endocervical tissue components. Unoccupied cytosol estrogen receptor levels as determined by Scatchard analysis of [3H]-estradiol binding data indicated a single class of high affinity binding sites for the epithelial-stromal complex (KD = 0.74 x 10(-9) M). Binding was specific for estrogen (estradiol greater than estriol greater than estrone) and unaffected by desoxycorticosterone, dihydrotestosterone and progesterone. Assays for total estrogen receptor verified that 71.6 +/- 5.3% of this 8S estrogen receptor is in the epithelial-stromal complex while the remaining approximately 28% is localized in the stroma and fibromuscular wall, with the cells of the complex containing the highest receptor concentration. In 5-day pseudopregnant and ovariectomized rabbits compared to estrous rabbits there was a 50% decrease in the cytosol estrogen receptor in the epithelial-stromal complex and a 30% decrease in the concentration of nuclear receptor. Cytosol and nuclear progesterone receptors were measured as an indicator of estrogen action in the rabbit endocervix. Cytosol progesterone receptor concentrations (fmol/mg DNA) in 5-day pseudopregnant and ovariectomized animals were reduced to approximately 35% of the concentration in estrous animals. Nuclear progesterone receptor concentrations decreased 65% in 5-day pseudopregnant and 90% in ovariectomized animals suggesting decreased receptor synthesis. Collectively these data support the concept that the rabbit endocervix may be directly regulated by estrogens.


Absence of B cells does not compromise intramembranous bone formation during healing in a tibial injury model.
Previous studies have generated conflicting results regarding the contribution of B cells to bone formation during physiology and repair. Here, we have investigated the role of B cells in osteoblast-mediated intramembranous anabolic bone modeling. Immunohistochemistry for CD45 receptor expression indicated that B cells had no propensity or aversion for endosteal regions or sites of bone modeling and/or remodeling in wild-type mice. In the endocortical diaphyseal region, quantitative immunohistology demonstrated that young wild-type and B-cell deficient mice had similar amounts of osteocalcin(+) osteoblast bone modeling surface. The degree of osteoblast-associated osteomac canopy was also comparable in these mice inferring that bone modeling cellular units were preserved in the absence of B cells. In a tibial injury model, only rare CD45 receptor positive B cells were located within areas of high anabolic activity, including minimal association with osterix(+) osteoblast-lineage committed mesenchymal cells in wild-type mice. Quantitative immunohistology demonstrated that collagen type I matrix deposition and macrophage and osteoclast distribution within the injury site were not compromised by the absence of B cells. Overall, osteoblast distribution during normal growth and bone healing via intramembranous ossification proceeded normally in the absence of B cells. These observations support that in vivo, these lymphoid cells have minimal influence, or at most, make redundant contributions to osteoblast function during anabolic bone modeling via intramembranous mechanisms.


Detection and discrimination of curvature in foveal and peripheral vision.
Curvature detection and discrimination were measured across the visual field in order to determine whether performance at a given eccentricity could be related to that at another by a simple change of magnification. Both types of task obeyed this concept, the critical variable being the rate at which magnification must increase as a function of eccentricity. The situation can be expressed in terms of the eccentricity (E2) at which magnification must be doubled to retain performance equivalent to that at the fovea. E2 values were 1.84-1.96 deg for the detection task and 1.42-2.27 deg for discrimination. These are similar to E2 values for vernier acuity and orientation discrimination, suggesting that all of these tasks share a common determining feature across the visual field, perhaps the distribution of neural elements selective for stimulus orientation.


A low temperature induced apoplastic protein isolated from Arachis hypogaea.
We describe the isolation, characterization and identification of an Arachis hypogaea cold shock protein (AHCSP33). AHCSP33 is secreted into the leaf apoplast during low temperature exposure. N-terminal sequence of AHCSP33 shows homology to Thaumatin-Like (TL) protein family (also called Group5 Pathogenesis-related (PR) proteins). AHCSP33 shows strongest homology (55%) at the N-terminus with the Rye TL protein (M(r) 25 k) which is an apoplastic protein and has antifreeze activity. Like several TL proteins, AHCSP33 is also targeted to the apoplast and persists for several days after low temperature treatment, although at reduced levels. AHCSP33 possesses intrachain disulfide bonds which is a well conserved feature of TL proteins. AHCSP33 might be involved in cryoprotecting proteins as it was shown to prevent freeze-induced denaturation of L-lactate dehydrogenase (LDH). Several features of AHCSP33 are consistent with its role in cryoprotection. It is a hydrophilic protein and is boiling stable. Hydrophilic amino acids constitute 80.4 mol%. Asp/Asn and Glu/Gln together constitute 20.8 mol%. AHCSP33 is glycosylated and exists as an oligomer in its native state.


Nucleophilic addition of potassium alkynyltrifluoroborates to D-glucal mediated by BF3 x OEt2: highly stereoselective synthesis of alpha-C-glycosides.
A convenient, mild and highly stereoselective method for C-glycosidation (alkynylation) of D-glucal with various potassium alkynyltrifluoroborates, mediated by BF3x OEt2 and involving oxonium intermediates, preferentially provides the alpha-acetylene glycoside products with good yields.


Spatial organization of the peripheral input to area 1 cell columns. I. The detection of 'segregates'.
Extracellular single neuron recording methods are used to study the RFs of neurons comprising area 1 cell columns in unanesthetized Macaca fascicularis monkeys. The RF data obtained in approximately radial microelectrode penetrations demonstrate that the RFs of neurons located within the same area 1 cell columns can differ strikingly, and that it is common for neighboring neurons to possess RFs differing greatly in size or configuration. However, the RF variations detected within a typical area 1 cell mini-column (single cell radial column) appear to be substantially less than the variations observed for nearby neurons lying in different minicolumns. The RF data obtained from arrays of penetrations suggest that the skin representation in the forelimb region of area 1 is organized in a discontinuous, step-like fashion: as a mosaic of discrete 600 micron wide radial cell columns--segregates. Although the RFs of neurons of a segregate can vary substantially in size and configuration, they all share in common a single small area on the skin. The boundaries of a segregate can be mapped precisely because, unlike the situation for neurons located within the same segregate, some of the neurons located on opposite sides of a segregate boundary (belonging to different segregates) have non-overlapping RFs. Furthermore, it appears that within any given segregate there is no systematic shift in RF location as the electrode advances through a sequence of minicolumns. Systematic RF shifts occurred only when the electrode traversed the boundary between neighboring segregates.


Effect of a topically applied neutralizing antibody against vascular endothelial growth factor on corneal allograft rejection of rat.
Studies in corneal transplant rejection remain important because acute immunologic rejection continues to be the leading cause of human corneal transplant failure. As the permeability of vessels and the neovascularization induce cells infiltration into the graft, we considered the possibility that vascular endothelial growth factor (VEGF), a potent permeability-increasing factor and angiogenesis-mediating factor, could participate in the immune response. As the established corneal transplant model for rejection, the corneal transplant between Lewis and Fisher rats has been reported. First, we evaluated VEGF production in the graft by immunohistochemical method in the animal model. Next, we tried to neutralize the effect of VEGF by topical administration of anti-VEGF antibody. We administered anti-VEGF antibody as eye drops for 10 days just after the transplantation of the established animal corneal transplant model. VEGF was strongly produced from the infiltrative cells into the graft. Anti-VEGF antibody significantly suppressed the acute rejection compared with saline or rabbit IgG. The inhibition of VEGF by topically applied neutralizing antibody is a new potential therapeutic strategy for the treatment of corneal transplantation.


Current standards and their relation to environmental behaviour and effects--the case of lead.
Lead enters the environment from a large number of point and diffuse sources. Several control options are available to reduce the input of lead to the environment and these have been utilised in the large number of European Community (EC) Directives adopted to control lead. The use of Environmental Quality Standards (EQS) is the most effective option to control pollutants entering an individual compartment from both point and diffuse sources since EQS take into account behaviour and effects of the pollutant in the environment. Future legislation to control pollution in one compartment should consider the potential implications for effects on the other compartments by using the "Best Environmental Options" approach and by combining the different options available to achieve environmental improvement.


Handheld reflectance confocal microscopy: Personalized and accurate presurgical delineation of lentigo maligna (melanoma).
The surgical treatment of lentigo maligna melanoma is associated with high rates of local recurrence. Handheld reflectance confocal microscopy (HH-RCM) allows for in vivo presurgical detection of subclinical lentigo maligna (melanoma) (LM/LMM). A single-center retrospective study from December 2015 to July 2017. Frequency and extent of negative surgical margins, and the diagnostic accuracy of presurgical mapping by HH-RCM was determined. Twenty-six consecutive patients with LM/LMM were included. In 45.8%, HH-RCM detected subclinical LM with a sensitivity of 0.90 and specificity of 0.86. The management was changed in two (7.7%) patients. Of the 24 remaining lesions, 95.8% were excised with negative margins with a mean histological margin of 3.1 and 5.3 mm for LM and LMM, respectively. At a mean follow-up of 36.7 months, there was one (4.8%) confirmed recurrence. Our method of presurgical delineation by HH-RCM appears to provide a reliable method for the surgical treatment of LM/LMM with a limited rate of overtreatment.


Expression of bone resorption regulators (RANK, RANKL, and OPG) in odontogenic tumors.
To investigate the expression of bone resorption regulators (receptor activator of nuclear factor kappa B [RANK], RANK ligand [RANKL], and osteoprotegerin [OPG]) in calcifying cystic odontogenic tumor (CCOT), adenomatoid odontogenic tumor (AOT), calcifying epithelial odontogenic tumor (CEOT), odontogenic myxoma (OM), and ameloblastic fibroma (AF). The expression of these mediators was evaluated by means of immunohistochemistry. All specimens demonstrated positive immunoreactivity to RANK, RANKL, and OPG. The quantification of these mediators in epithelium revealed a similar pattern of expression for RANKL and OPG in CCOT, AOT, CEOT, and AF. With regard to stromal/mesenchymal cells, the majority of AOT and CCOT cases showed a higher content of OPG than RANKL, whereas CEOT, OM, and especially AF had a tendency to present a greater content of RANKL than OPG. Our data indicate that the CCOT, AOT, CEOT, OM, and AF cell constituents express key regulators of bone metabolism that might locally modulate tumor-associated bone resorption.


Astrocytes protect the CNS: antigen-specific T helper cell responses are inhibited by astrocyte-induced upregulation of CTLA-4 (CD152).
Astrocytes are the first cells that are encountered by T cells invading the central nervous system (CNS) by crossing the blood-brain barrier. We show that primary astrocytes contribute to the immune privilege of the CNS by suppressing Th1 and Th2 cell activation, proliferation and effector function. Moreover, this astrocyte-mediated inhibition of Th effector cells was effective on already activated, proliferating cells. Transforming growth factor (TGF)-beta secreted by astrocytes or T cells was not the major factor in the inhibition. The inhibition of T-cell proliferation induced by astrocytes was mainly mediated by upregulation of CTLA-4 on already activated T cells, which occurred both with and without cell-cell contact. Upregulation of the inhibitory molecule CTLA-4 on autoreactive Th cells, as mediated by astrocytes, thus represents a novel mechanism for securing the immune privilege of the CNS.


Recovery of plants from "Near-Lethal" stress.
This study reports on the dieback and recovery of red-osier dogwood, Cornus sericea L. plants from "near-lethal" (NL, sublethal) stress after varying lengths of post-stress environment (PSE). Intact dormant stems were subjected to 47° C for one hour during either October, November or December, and then placed into either constant 0° C or 23° C (dark condition) or kept under natural conditions at Corvallis, OR. Plants exposed to NL-heat stress in October died prior to 9 weeks of 0° C PSE, while none of the plants from other PSE treatments showed signs of injury. For plants exposed to NL-heat stress during November and December, stemdieback occurred at 0° C after 12 and 15 weeks, respectively. None of the plants from the other PSE treatments were injured. Post-stress temperatures of 0° or 5° C following NL-heat in October were lethal while temperatures above 10° C allowed recovery. Post-stress exposure to 0° C injured excised stems within 48 h, whereas irreversible damage to whole plants occurred by two weeks. Dormant plants exposed in October to other stresses, e.g., freezing temperature and hydrogen cyanamide, at NL dosages showed that these stresses also caused plant dieback at 0° C and little or no dieback at 23° C PSE.


Hymenoptera sting hypersensitivy: IgE, IgG and haemagglutinating antibodies to bee venom constituents in relation to exposure and clinical reaction to bee stings.
High levels of IgE antibodies (Ab) to bee venom constituents were mainly found in patients with bee sting hypersensitivity, whereas the sera of bee keepers usually contained high levels of IgG Ab and haemagglutinins, representing blocking antibody activity. In bee keepers there was a positive correlation between the degree of severity of an adverse reaction to bee stings and IgE Ab, a negative one between the severity of reaction and IgG Ab and haemagglutinins, a positive one between the number of stings per season and IgG Ab and haemagglutinins, and negative one between the number of stings and IgE Ab. This suggests a mutual dependence of the production of IgE Ab and blocking Ab in a regularly exposed population. No such correlation was found in bee sting-allergic patients, indicating that other factors influence the severity of reaction in this only sporadically exposed group. The values of IgG Ab and haemagglutinins correlated well with each other, with IgG Ab giving a better correlation with severity of reaction and number of stings than the haemagglutinins.


Methods to Determine the Effects of MIF on In Vitro Osteoclastogenesis Using Murine Bone Marrow-Derived Cells and Human Peripheral Blood Mononuclear Cells.
Osteoclasts are the only cells that are capable of resorbing bones, and they are involved in multiple diseases and disorders. This chapter will describe several in vitro osteoclastogenesis methods, which allows further investigation of molecular mechanisms of osteoclastogenesis in normal physiological and disease conditions. This chapter includes a protocol for isolating osteoclast progenitors from mouse bone marrow and human peripheral blood, as well as obtaining murine osteoblasts for the coculture system. Furthermore, culture and identification of multinucleated osteoclasts in vitro is also described in this chapter.


Detection and differentiation of inflammatory versus fibromatous Crohn's disease strictures: prospective comparison of 18F-FDG-PET/CT, MR-enteroclysis, and transabdominal ultrasound versus endoscopic/histologic evaluation.
Differentiation between inflammatory and fibromatous strictures in Crohn's disease (CD) is difficult but crucial for therapeutic decisions. The aim of this study was to assess the best noninvasive imaging method for the detection and differentiation of inflammatory and fibromatous stenoses in CD in comparison to endoscopic and histologic evaluation. Patients with suspected CD strictures were included. According to a formalized endoscopic and histologic protocol, strictures were classified as inflammatory, mixed, and fibrostenotic. Strictures were further analyzed using fluorine 18-labeled fluoro-2-deoxy-D-glucose ((18) FDG) / positron emission tomography (PET) low-dose computed tomography (CT), magnetic resonance (MR) enteroclysis and transabdominal ultrasound using standardized scoring systems. Thirty patients with 37 strictures were evaluated (inflamed n = 22; mixed n = 12, fibromatous n = 3). (18) FDG-PET/CT detected 81%, MR-enteroclysis 81%, and ultrasound 68% of the strictures. Correct differentiation rates of strictures were 57% for MRE, 53% for (18) FDG-PET/CT, and 40% for ultrasound. Differences of detection rates and differentiation rates were not statistically significant. When combining transabdominal ultrasound with (18) FDG-PET/CT or MR-enteroclysis all strictures that required invasive treatment were detected. Detection rates of the strictures were not significantly different between (18) FDG-PET/CT, MR-enteroclysis, and ultrasound. Despite good stricture detection rates relating to our gold standard, (18) FDG-PET/CT nor MR-enteroclysis nor ultrasound can accurately differentiate inflamed from fibrotic strictures. A combination of MR-enteroclysis and ultrasound as well as a combination of (18) FDG-PET/CT and ultrasound resulted in a 100% detection rate of strictures requiring surgery or endoscopic dilation therapy, suggesting the combination of these methods as an alternative to endoscopy at least in the group of patients not able to perform an adequate bowel preparation.


ACTH treatment in intractable seizures of childhood.
Between 1980 and 1989, 21 children suffering from intractable seizures other than infantile spasms were treated with intramuscular ACTH at the Children's Hospital Camperdown. Five patients had two courses of ACTH therapy, 24% of patients had a good response (group A), 56% responded transiently (group B) and 20% did not respond (group C). Group A had normal development and no neurological deficits prior to seizures. A favourable response was not observed in patients with partial seizures, 90% of the patients who responded had a recurrence of seizures. Mean time to recurrence was 9.0 +/- 7.3 months in group A and 1.6 +/- 2.0 months in group B. Hypokalaemia, hypertension and infection were found in 42.9%, 33.3% and 19.1% respectively. ACTH also had effects on concurrent anti-epileptic drug levels.


Risk of injury from alcohol, marijuana and other drug use among emergency department patients.
Alcohol is known to be associated with injury, but little is known of combined use of alcohol and other drugs on injury; especially important for marijuana, given increasing legalization of use in the U.S. and Canada. Probability samples of patients 18 and older were interviewed in the emergency department at two sites in Vancouver and one in Victoria, BC (n=1191 injured and 1613 non-injured patients). Case-control and case-crossover analyses were used to analyze risk of injury, based on self-reported alcohol and drug use (marijuana, stimulants, depressants) prior to injury. Risk of injury was significantly elevated (p<0.001) for alcohol use alone in both case-control (OR=2.72) and case-crossover analyses (OR=2.80) but not for any of the three drug classes. The interaction of alcohol with each class of drug was tested, and marginally significant only for marijuana in case-control analysis (OR=4.42; p=0.088). The interaction of alcohol and two or more drugs was also significant in case-control analysis (OR=03; p=0.035). The volume of alcohol consumed prior to injury was greater for those also using drugs during this time and positively associated with the number of drugs reported. Given the potential issues involved with both case-control and case-crossover study designs, the inconsistent findings suggest caution in reaching any definite conclusion regarding whether there is extra risk related to combined use of alcohol and marijuana, and is an important area for future research.


Achilles tendon lengthening in cerebral palsy: comparison of inpatient versus ambulatory surgery.
The proper use of outpatient surgery is still being defined. In similar groups of cerebral palsied children, the results of Achilles tendon lengthening were compared in those having inpatient versus outpatient surgery. No significant anesthesia or surgical complication occurred in either group, and independent ambulation in casts was achieved at similar times. Pain medication requirements (based on an analgesic potency scale) averaged 9.5 +/- 6.0 for the children having outpatient surgery compared with 25.8 +/- 22.8 for those having inpatient surgery (p less than 0.02). Outpatient Achilles tendon lengthening provides psychological and economic advantages without compromise of surgical results.


Effects of horizontal compared to vertical-based plyometric jump training on semi-professional soccer player's performance.
This study aimed to compare the effects of horizontal (HJ) and vertical (VJ)-based plyometric jump training on male semi-professional soccer player's performance (e.g., change-of-direction speed [5-0-5 test]; 10-m, 20-m, and 30-m linear sprint speed). A parallel-study design was conducted. Participants were organized into HJ (n = 10) or VJ (n = 9) during 12 weeks. Measures of athletic performance were obtained in four phases: (i) before and (ii) end of the pre-season, (iii) during (weeks 7th), and (iv) after the intervention. The within-group analysis revealed that both HJ and VJ improved change of direction ([Formula: see text] = 27.783; p < 0.001 ([Formula: see text] = 21.635; p < 0.001),), 10-m linear sprint time ([Formula: see text] = 28.576; p < 0.001), 20-m linear sprint time ([Formula: see text] = 28.969, p < 0.001), and 30-m linear sprint time ([Formula: see text] = 26.143; p < 0.001). Similarly, the VJ-group also imposed significant changes on 5-0-5 time, 10-m linear sprint time ([Formula: see text] = 25.787; p < 0.001), 20-m linear sprint time ([Formula: see text] = 24.333, p < 0.001), and 30-m linear sprint time ([Formula: see text] = 22.919; p < 0.001). Between-group analysis revealed no significant differences in any of the assessment moments. HJ and VJ plyometric jump training are effective for improving the change-of-direction and a linear sprint of semi-professional players with no difference between types of intervention.


Trichilemmal cyst in the pulp of the index finger: a case report.
We reported a case of trichilemmal cyst in the pulp of the index finger. Histopathological features and unusual MR images are discussed.


Combining education and income into a socioeconomic position score for use in studies of health inequalities.
In studies of social inequalities in health, there is no consensus on the best measure of socioeconomic position (SEP). Moreover, subjective indicators are increasingly used to measure SEP. The aim of this paper was to develop a composite score for SEP based on weighted combinations of education and income in estimating subjective SEP, and examine how this score performs in predicting inequalities in health-related quality of life (HRQoL). We used data from a comprehensive health survey from Northern Norway, conducted in 2015/16 (N = 21,083). A composite SEP score was developed using adjacent-category logistic regression of subjective SEP as a function of four education and four household income levels. Weights were derived based on these indicators' coefficients in explaining variations in respondents' subjective SEP. The composite SEP score was further applied to predict inequalities in HRQoL, measured by the EQ-5D and a visual analogue scale. Education seemed to influence SEP the most, while income added weight primarily for the highest income category. The weights demonstrated clear non-linearities, with large jumps from the middle to the higher SEP score levels. Analyses of the composite SEP score indicated a clear social gradient in both HRQoL measures. We provide new insights into the relative contribution of education and income as sources of SEP, both separately and in combination. Combining education and income into a composite SEP score produces more comprehensive estimates of the social gradient in health. A similar approach can be applied in any cohort study that includes education and income data.


The impact of ambient air pollutants on childhood respiratory system disease and the resulting disease burden: a time-series study.
The effects of air pollution on human health have long been a hot topic of research. For respiratory diseases, a large number of studies have proved that air pollution is one of the main causes. The purpose of this study was to investigate the risk of hospitalization of children with respiratory system diseases (CRSD) caused by six pollutants (PM2.5, PM10, NO2, SO2, CO, and O3) in Hefei City, and further calculate the disease burden. In the first stage, the generalized additive models were combined with the distributed lag non-linear models to evaluate the impact of air pollution on the inpatients for CRSD in Hefei. In the second stage, this study used the cost-of-illness approach to calculate the attributable number of hospitalizations and the extra disease burden. Overall, all the six kinds of pollutants had the strongest effects on CRSD inpatients within lag10 days. SO2 and CO caused the highest and lowest harm, respectively, and the RR values were SO2 (lag0-5): 1.1 20 (1.053, 1.191), and CO (lag0-6): 1.002 (1.001, 1.003). During the study period (January 1, 2014 to December 30, 2020), the 7-year cumulative burden of disease was 36.19 million CNY under the WHO air pollution standards. In general, we found that six air pollutants were risk factors for CRSD in Hefei City, and create a huge burden of disease.


Tetralogy of Fallot with aortopulmonary window.
A patient with tetralogy of Fallot associated with aortopulmonary window has been documented. The association was found in one case out of 350 consecutive cases of Fallot's tetralogy evaluated cineangiographically. Since tetralogy of Fallot may be completely masked by the aortopulmonary window it is suggested that a right ventricular angiogram should be obtained in all patients with an aortopulmonary window.


Increased Photovoltaic Performance in Polymer-Oligothiophene-[6,6]-Phenyl-C61 -Butyric Acid Methylester Ternary Blend Films.
The introduction of oligothiophenes (b-5T and b-5TB) improved the performance of F85TB:PCBM bulk heterojunction OPV cells due to improved UV-vis absorption and the well-matched cascade energy levels between components.


GC-MS and GC-MS/MS measurement of malondialdehyde (MDA) in clinical studies: Pre-analytical and clinical considerations.
Malondialdehyde (MDA; 1,3-propanedial, OHC-CH2-CHO) is one of the most frequently measured biomarkers of oxidative stress in plasma and serum. L-Arginine (Arg) is the substrate of nitric oxide synthases (NOS), which convert L-arginine to nitric oxide (NO) and L-citrulline. The Arg/NO pathway comprises several members, including the endogenous NOS-activity inhibitor asymmetric dimethylarginine (ADMA) and its major metabolite dimethyl amine (DMA), and nitrite and nitrate, the major NO metabolites. Reliable measurement of MDA and members of the Arg/NO pathway in plasma, serum, urine and in other biological samples, such as saliva and cerebrospinal fluid, is highly challenging both for analytical and pre-analytical reasons. In our group, we use validated gas chromatography-mass spectrometry (GC-MS) and gas chromatography-tandem mass spectrometry (GC-MS/MS) methods for the quantitative determination in clinical studies of MDA as a biomarker of oxidative stress, and various Arg/NO metabolites that describe the status of this pathway. Here, the importance of pre-analytical issues, which has emerged from the use of GC-MS and GC-MS/MS in clinico-pharmacological studies, is discussed. Paradigmatically, two studies on the long-term oral administration of L-arginine dihydrochloride to patients suffering from peripheral arterial occlusive disease (PAOD) or coronary artery disease (CAD) were considered. Pre-analytical issues that were addressed include blood sampling, plasma or serum storage, study design (notably in long-term studies), and the alternative of measuring MDA in human urine.


HIV infection in children: sizing up the paediatric problem.
Cases of paediatric AIDS have increased each year in the USA, as the disease has spread to the heterosexual community. In the USA the geographic distribution of perinatal AIDS cases mirrors the distribution of cases in women. To date, 503 HIV antibody positive women have been reported in the UK. It is likely that the increasing number of seropositive women will be reflected in an increase in the number of reports of perinatal HIV infection and AIDS. Although screening of blood donors and blood products has stopped further increase in infections from this route, as transfusion-infected children become symptomatic the burden on paediatric services will increase.


Pre-treatment serum albumin and mutational burden as biomarkers of response to immune checkpoint blockade.
The effects of cytokine and protein stabilizing carriers, such as serum albumin, on tumor response to immune checkpoint blockade (ICB) is not well understood. By examining 1714 patients across 16 cancer types, we found that high pretreatment serum albumin level predicts favorable tumor radiographic response following ICB treatment in a dose-dependent fashion. Serum albumin is a candidate biomarker that can be combined with tumor mutational burden (TMB) for additional predictive capacity, and the tumor response rate to ICB was ~49% in the albumin-high/TMB-high group.


Asymmetric synthesis of Boc-N-methyl-p-benzoyl-phenylalanine. Preparation of a photoreactive antagonist of substance P.
The asymmetric synthesis of (S)-Boc-N-methyl-p-benzoyl-phenylalanine was performed by alkylation of sultam Boc-sarcosinate. The levorotatory sultam led to (S)-Boc-N-methyl amino acids with high optical purity. This photoreactive amino acid was incorporated into the sequence of a Substance P peptide antagonist. Comparison of the affinity and antagonistic properties of Biotinyl-apa-[D-Pro9, MePhe(pBz)10, Trp11]SP for human tachykinin NK-1 receptor demonstrated that this photoreactive antagonist should be a suitable tool for photolabelling studies.


Histological evaluation of direct pulp capping of rat pulp with experimentally developed low-viscosity adhesives containing reparative dentin-promoting agents.
This study examines the wound healing process in exposed rat pulp when capped with experimental adhesive resin systems. Experimental adhesive resin system for direct pulp capping was composed of primer-I (PI), -II (PII), and -III (PIII) and an experimental bonding agent (EBA). PI was Clearfil(®) SE Bond(®)/Primer (CSP) containing 5.0 wt% CaCl2, PII was PI containing 10 wt% nanofiller (Aerosil(®) 380), and PIII was CSP containing 5.0 wt% of compounds of equal moles of synthetic peptides (pA and pB) derived from dentin matrix protein 1. EBA was Clearfil(®) SE Bond(®)/Bond (CSB) containing 10 wt% hydroxyapatite powders. Three experimental groups were designed. PI was assigned to experimental Groups 1 and 3. PII was assigned to experimental Groups 2 and 3. PIII and EBA were assigned to all experimental adhesive groups. Control teeth were capped with calcium hydroxide preparation (Dycal(®)), and CSP and CSB were applied to the cavity. The rats were sacrificed after each observation period (14, 28, 56, and 112 days). The following parameters were evaluated: pulp tissue disorganization, inflammatory cell infiltration, reparative dentin formation (RDF), and bacterial penetration. There were no significant differences among all the groups for all parameters and all observation periods (p>0.05, Kruskal-Wallis test). All groups showed initial RDF at 14 days postoperatively and extensive RDF until 112 days postoperatively. Groups 2 and 3 demonstrated higher quantity of mineralized dentin bridge formation compared with Group 1. Addition of nanofillers to the primer was effective in promoting high-density RDF. Experimentally developed adhesive resin systems induce the exposed pulp to produce almost the same quantity of reparative dentin as calcium hydroxide. However, we need further studies to elucidate whether the same results could be obtained in humans.


Use of differentiation-inducing agents in the myelodysplastic syndrome and acute non-lymphocytic leukemia.
The use of chemical agents that induce differentiation of malignant cells to normal cells has held great promise as an adjunct to standard chemotherapy. In vitro data has shown that 13-cis-retinoic acid can differentiate certain leukemia cell lines (e.g., HL-60) into stable granulocyte cells. In this study, oral 13-cis-retinoic acid was administered to four patients with the myelodysplastic syndrome (MDS) and to four patients with acute nonlymphocytic leukemia (ANLL). None of the MDS patients showed an hematologic response to the drug, while three of four ANLL patients responded with normalized peripheral blood counts. The side effects of the drug at 80-120 mg/d (dry skin, cheilitis, epistaxis) were self limiting.


Effect of Selective Serotonin Reuptake Inhibitor Use in Pregnancy on Emotional Health of Children.
I read with interest the article by Lupattelli et al., "Effect of Time-Dependent Selective Serotonin Reuptake Inhibitor Antidepressants During Pregnancy on Behavioral, Emotional, and Social Development in Preschool-Aged Children,"1 which describes the effects of selective serotonin reuptake inhibitor (SSRI) use in pregnancy on mental health in offspring, in the March issue of the Journal. The investigators found that SSRI use in late pregnancy resulted in greater risk for anxious/depressed behaviors in children by 5 years of age compared with unexposed children.


How patients with heart failure are managed in the United Kingdom.
Heart failure is a major cause of morbidity and mortality world wide. In the UK it is estimated to affect one in ten octogenarians. This obviously imposes a large burden on our health care services, and the ageing of our population will only exacerbate this. In this article we have attempted to provide a general overview of the day to day management of these patients in the United Kingdom.


Hypervascularized Large Vestibular Schwannomas: Single-Center Experience in a Series of Forty Cases.
Vestibular schwannomas (VS) are usually hypovascularized benign tumors. Large VS (Koos grade IV) with unusual vascular architecture are defined as hypervascular (HVVS); the excessive bleeding during microsurgery has a negative impact on results. Forty consecutive patients were operated on for HVVS (group A). A tendency to bleed and adherence of capsule to nervous structures were evaluated by reviewing intraoperative video records. The cisternal facial nerve (FN) position was reported. Microsurgical removal was classified as total, near-total, subtotal, or partial and the MIB-1 index was evaluated in all. FN results were classified according to the House-Brackmann scale. Results of Group A were compared with those of 45 patients operated on for large low-bleeding VS (group B). Mean tumor diameter was 3.81 cm in group A and 3.58 cm in group B; the mean age was 42.4 and 56.3 years, respectively. The mean American Society of Anesthesiologists Physical Status Scale class of group A was 1.67 versus 2.31 of group B (P < 0.01). Total or near-total resection was accomplished in 76.5% of group A versus 73.3% of group B. Tight capsule adhesion was observed in 67.5% of group A versus 57.8% of group B. Mean MIB-1 was 1.25% and 1.08%, respectively.FN anatomic preservation was possible in 84.6% of group A versus 95.5% of group B; 67.5% of group A had HB grade I or II FN outcome versus 93.3% of group B (P < 0.001). In group A, 8 patients (20.0%) experienced transient postoperative complications versus 4.4% of group B. Recurrence/regrowth was observed in 4 patients in group A versus 1 in group B. Intraoperative video for classification of HVVS was used. Microsurgery of large HVVS was associated with higher (usually transient) complications and recurrence/regrowth rates and poorer FN outcome, especially in patients with tight capsule adhesion.


Increasing eligibility for nipple-sparing mastectomy.
Eligibility for nipple-sparing mastectomy (NSM) varies widely on the basis of patient and tumor factors. Review of patients undergoing NSM from June 2007 to December 2012 at our institution was performed. Patient and tumor characteristics, complications, and recurrences were collected. NSM from 2007 to 2010 and 2011 to 2012 were compared to assess trends in eligibility and outcomes over time. NSM was performed on 645 breasts in 370 patients. Indications were risk reduction in 330 (51.2 %), invasive cancer in 226 (35.0 %), and ductal carcinoma-in situ in 89 (13.8 %) breasts. Fifty-one (13.8 %) patients had positive lymph nodes. Twenty-seven (7.3 %) patients received neoadjuvant chemotherapy. Forty-eight (7.4 %) breasts had prior radiotherapy. Total nipple necrosis occurred in 11 (1.7 %) breasts. Twenty-four (3.7 %) breasts had nipples removed as a result of positive subareolar/nipple margins. At 22 months' mean follow-up, local recurrence occurred in 4 of 156 (2.6 %) breasts operated on for cancer through 2011. No recurrences involved the nipple. NSM performed in 2011-2012 (n = 475) compared to 2007-2010 (n = 170), were more often for cancer, in patients with higher body mass index, and on larger breasts (p < 0.001). There was no significant difference in total nipple necrosis rates between groups. Nipple loss due to positive subareolar/nipple margins was significantly less in 2011-2012 (p = 0.027). Eligibility for NSM has expanded to include women with higher body mass index and larger breasts, with no increase in nipple loss due to ischemia. Rates of positive subareolar margins have decreased over time, even though NSM is being performed more frequently for cancer, suggesting improved patient selection.


Sileneisabellae (Caryophyllaceae), a new campion species from serpentine soils of Albania.
The new species Sileneisabellae is described and illustrated from the Skënderbëut mountain range of central Albania. It grows on the ultramafic mountain slopes around Qafë Shtamë, in the understorey of open Pinusnigra forests and in the rocky grasslands above the forest belt, at 1000-1600 m a.s.l. Sileneisabellae is a serpentine endemic likely belonging to section Elisanthe (Fenzl ex Endl.) Ledeb. and shows affinities with the widespread European species S.noctiflora L. It is sharply distinct from the latter species in habit, stem and leaf pubescence, morphology, and biology of the flowers and length of the carpophore. Moreover, the ecology of the two taxa is also contrasting, being S.noctiflora a synanthropic-ruderal, mostly in lowlands. Weaker similarities were also observed with the south European subalpine taxa of the group of S.vallesia L. of section Auriculatae (Boiss.) Schischk., though these are not likely to reflect a real systematic affinity.


Lectin binding studies on a glycopolymer brush flow-through biosensor by localized surface plasmon resonance.
A localized surface plasmon resonance biosensor in a flow-through configuration was applied for investigating kinetics of lectin binding to surface-grafted glycopolymer brushes. Polycarbonate filter membranes with pore sizes of 400 nm were coated with a 114-nm thick gold layer and used as substrate for surface-initiated atom-transfer radical polymerization of a glycomonomer. These grafted from glycopolymer brushes were further modified with two subsequent enzymatic reactions on the surface to yield an immobilized trisaccharide presenting brush. Specific binding of lectins including Clostridium difficile toxin A receptor domain to the glycopolymer brush surface could be investigated in a microfluidic setup with flow-through of the analytes and transmission surface plasmon resonance spectroscopy. Graphical abstract Glycopolymer brushes serve as high affinity ligands for lectin and toxin interactions in a sensitive, disposable flow-through LSPR biosensor.


Association between body mass index and long-term clinical outcomes in patients with non-valvular atrial fibrillation taking oral anticoagulants.
The association between body mass index (BMI) and clinical outcomes of patients with non-valvular atrial fibrillation (NVAF) taking oral anticoagulants (OACs) are controversial, and we thus analyzed the large registry data to elucidate them. We conducted a historical cohort study at 71 centers in Japan and included outpatients with NVAF taking vitamin K antagonists (VKAs). Physicians in charge could change VKAs to direct OACs based on their judgement during follow-up period. We categorized patients into four BMI groups (kg/m2): underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (30 ≤ BMI). The effects of each BMI group relative to the normal weight group on clinical outcomes consisting of all-cause death, ischemic events, and bleeding events were estimated using Cox proportional hazard models adjusting for potential confounders. We also constructed restricted cubic spline regression model adjusted by multivariable Cox proportional hazard models. We included 6927 patients consisting of an underweight (n = 386), normal weight (n = 3785), overweight (n = 2174), and obese (n = 582) groups. The median follow-up period was 3.9 years. In the underweight group, the adjusted hazard ratios (HRs) for all-cause death and ischemic events were 1.75 (1.30-2.34) and 1.61 (1.04-2.50). The HR for all-cause death was 0.63 (0.49-0.82) in the overweight group. Restricted cubic spline regression models confirmed that lower BMI showed significantly higher risks for all-cause death and ischemic events. Among NVAF patients taking OACs, underweight patients had higher risks of all-cause death and ischemic events than other patients. Overweight patients had lower risk of all-cause death.


In-solution staining and arraying method for the immunofluorescence detection of γH2AX foci optimized for clinical applications.
Immunofluorescence quantification of γH2AX foci is a powerful approach to quantify DNA double-strand breaks induced by cancer therapy or accidental exposure to ionizing radiation. Here we report a modification to the γH2AX immunofluorescence labeling method, whereby cells are stained in-solution before being spotted and fixed onto microscope slides. Our modified method allows arraying of 16 patient samples/slide ready for foci counting in 2 h and demonstrated reliably detection of γH2AX foci in mononuclear cells prepared from patients who had undergone radiation therapy.


Factors associated with attendance at the postpartum blood pressure visit in pregnancies complicated by hypertension.
Women with hypertensive disorders of pregnancy should have a blood pressure evaluation no later than 7-10 days after delivery. The objective of this study was to identify the factors associated with patient attendance at the postpartum blood pressure follow-up visit. This was a retrospective cohort study of postpartum women who had a hypertensive disorder of pregnancy. Postpartum follow-up rates were recorded, and characteristics of women who attended a postpartum visit for blood pressure evaluation were compared to women who did not return for the visit. Multiple logistic regression was performed. Characteristics of women who returned for a blood pressure visit. There were 378 women who met inclusion criteria; 193(51.1%) attended the blood pressure visit. Women who returned were older and more likely to have preeclampsia, severe features, magnesium sulfate use, or severe hypertension during hospitalization. They were less likely to have gestational hypertension. Adjusted analysis demonstrated that black/non-Hispanic women (OR 0.53, 95% CI 0.34-0.83), the presence of any preeclampsia diagnosis (OR 2.19, 95% CI 1.03-4.81), and whether the woman underwent a cesarean delivery (OR 3.06, 95% CI 1.85-5.14) remained significant factors in predicting adherence. Women who returned for a blood pressure visit were more likely to have had significant hypertensive disease or a cesarean delivery. Non-Hispanic black women had the lowest rate of follow-up. Given black women have the highest rates of maternal morbidity and mortality nationwide, effective interventions to increase follow-up for them are needed.


Regional differences in the inhibition of L-glutamate and L-aspartate sodium-dependent high affinity uptake systems in rat CNS synaptosomes by L-trans-pyrrolidine-2,4-dicarboxylate, threo-3-hydroxy-D-aspartate and D-aspartate.
The sodium-dependent high affinity transport of L-[3H]glutamate and L-[3H]aspartate into synaptosomal fractions prepared from three different regions was employed to investigate the inhibitors L-trans-pyrrolidine-2,4-dicarboxylate, threo-3-hydroxy-D-aspartate and D-aspartate. These substances showed regional heterogeneity as inhibitors of sodium-dependent high affinity uptake of L-glutamate and L-aspartate. L-trans-Pyrrolidine-2,4-dicarboxylate was a more potent inhibitor of the uptake of L-glutamate than of L-aspartate in the cortex (IC50 8 microM vs L-glutamate and 13 microM vs L-aspartate) and cerebellum (IC50 4 microM v L-glutamate and 8 microM vs L-aspartate). threo-3-Hydroxy-D-aspartate was a more potent inhibitor of the uptake of L-glutamate than of L-aspartate in the cortex (IC50 9 microM vs L-glutamate and 13 microM vs L-aspartate) and hippocampus (IC50 6 microM v L-glutamate and 11 microM v L-aspartate). D-Aspartate was a more potent inhibitor of the uptake of L-glutamate than of L-aspartate only in the cortex (IC50 8 microM vs L-glutamate and 15 microM vs L-aspartate). These results thus support other evidence that there is regional heterogeneity in sodium-dependent high affinity acidic amino acid uptake sites in the brain.


Triple-Layer Plastic Bags Protect Dry Common Beans (Phaseolus vulgaris) Against Damage by Acanthoscelides obtectus (Coleoptera: Chrysomelidae) During Storage.
Fumigated dry common beans (Phaseolus vulgaris L.) that were artificially infested with Acanthoscelides obtectus Say, and others that were not artificially infested, were stored in hermetic triple-layer PICS (Lela Agro, Kano, Nigeria) or woven polypropylene (PP) bags for 6 mo at ambient laboratory temperature conditions of 22.6 ± 1.9°C and 60.1 ± 4.3% relative humidity. In an additional trial, beans contained in PP bags were treated with Actellic Super dust before introducing A. obtectus. Moisture content, number of live adult A. obtectus, seed damage, weight loss, and seed germination were determined at monthly intervals. At 6 mo, beans stored in PICS bags retained higher moisture than those stored in PP bags, but in all treatments the moisture level remained below that recommended for safe storage of beans. In the PICS bags, proliferation of A. obtectus did not proceed and at 6 mo, beans stored in these bags did not have insect-inflicted seed damage or weight loss. In contrast, seed damage and weight loss in PP bags exceeded economic threshold after 1 mo in the absence of Actellic Super dust (Syngenta Crop protection AG, Basle, Switzerland), and after 2 mo in the presence of it. Germination of beans stored in PP bags decreased greatly whereas the beans stored in PICS bags did not show reduced germination. Chemical free storage of common beans in PICS bags protects them against damage by A. obtectus.


CD4+IL9+ (Th9) cells as the major source of IL-9, potentially modulate Th17/Treg mediated host immune response during experimental cerebral malaria.
Th9, a new subgroup of CD4+T cells is characterized by its specific cytokine IL-9, is a critical factor in allergic diseases, cancers and parasitic infections. This study aimed to explore the potential roles of Th9 cells in the immunopathogenesis of ECM. In splenocytes sourced from uninfected, PbA and Py infected mice, Th9 cells were characterised by flow cytometry, cell sorting and qPCR. Enhancement of CD4+IL-9+ (Th9) cells were observed in both the infections, which corroborated with increased expression of the differentiating transcription factors. Moreover, crucial cytokine receptors (IL-4R, TGF-βR, IL-6R) as well as chemokine receptors (CCR3, CCR6 and CCR7) and activation marker (CD96), demonstrated elevation upon PbA infection in splenic Th9 cells. Furthermore, Neutralization of IL-9 along with IL-6 enhanced host survivability, reduced mean neurological score of ECM. However, anti- IL-9 treatment also down regulated frequency of Th17 cells, and its transcription factors pSTAT3, RORγT along with depleted Il-1β and Il-6 expression. In sum, understanding how IL-9 producing CD4+ T-cells can alter Th17/Treg ratio and by that modulate host's immune response, could pave the way for developing immunomodulatory interventions against cerebral malaria.


Interaction of glycine with isolated hydroxyl groups at the silica surface: first principles B3LYP periodic simulation.
The adsorption of a glycine molecule on a model silica surface terminated by an isolated hydroxyl group has been studied ab initio using a double-zeta polarized Gaussian basis set, the hybrid B3LYP functional, and a full periodic treatment of the silica surface/glycine system. The hydroxylated silica surface has been simulated using either a 2D slab or a single polymer strand cut out from the (001) surface of an all-silica edingtonite. A number of B3LYP-optimized structures have been found by docking glycine on the silica surface exploiting all possible hydrogen bond patterns. Whereas glycine is generally adsorbed in its neutral form, two structures show glycine adsorbed as a zwitterion, the surface playing the role of a "solid solvent" whereas intrastrand hydrogen bond cooperativity stabilizes the zwitterions. The adsorbed zwitterionic structures are no longer formed at a lower glycine coverage as simulated by enlarging the unit cell so as to break intrastrand hydrogen bonds, showing the importance of H-bond cooperativity in stabilizing the zwitterionic forms. Each structure has been characterized by computing its harmonic vibrational spectrum at the Gamma point, which also allowed us to calculate the free energy of adsorption. The experimental infrared features of chemical-vapor-deposited glycine on a silica surface are in agreement with those computed for glycine adsorbed in its neutral form and engaging three hydrogen bonds with the surface silanols, two of them involving the C=O bond and one originating from the glycine OH group. The NH(2) group plays only a minor role as a weak hydrogen bond donor.


Effects of neurokinin receptor antagonists on L-dopa induced bladder hyperactivity in normal conscious rats.
The urodynamic effects of intrathecal neurokinin (NK) receptor blockade on L-dopa-induced bladder hyperactivity were investigated in a rat model. Continuous cystometry was performed in normal, conscious, female Sprague-Dawley rats. In rats pretreated with intraperitoneal carbidopa 50 mg./kg., intraperitoneal L-dopa 50 mg./kg. caused bladder hyperactivity that could be attenuated by intrathecal administration of the NK1 receptor selective antagonist SR 140,333 (2 nmol.), whereas the NK2 receptor selective antagonist SR 48,968 (2 nmol.) failed to do so. Combination of SR 140,333 (2 nmol.) and SR 48,968 (2 nmol.), which by itself decreased micturition pressure, practically abolished the L-dopa-induced hyperactivity. The present results suggest that tachykinins, via stimulation of NK1 (and/or NK2) receptors, are involved in L-dopa-induced bladder hyperactivity, most probably at the spinal level. This implies tachykinin involvement in the supraspinal pathways that control the sacral parasympathetic center innervating the urinary bladder. It also implies that spinal NK receptors are a possible target for drugs aimed for elimination of bladder hyperactivity mediated via these pathways.


Human embryonic or adult stem cells: an overview on ethics and perspectives for tissue engineering.
Over the past few years, research on animal and human stem cells has experienced tremendous advances which are almost daily loudly revealed to the public on the front-page of newspapers. The reason for such an enthusiasm over stem cells is that they could be used to cure patients suffering from spontaneous or injuries-related diseases that are due to particular types of cells functioning incorrectly, such as cardiomyopathy, diabetes mellitus, osteoporosis, cancers, Parkinson's disease, spinal cord injuries or genetic abnormalities. Currently, these diseases have slightly or non-efficient treatment options, and millions of people around the world are desperately waiting to be cured. Even if not any person with one of these diseases could potentially benefit from stem cell therapy, the new concept of "regenerative medicine" is unprecedented since it involves the regeneration of normal cells, tissues and organs which could allow to treat a patient whereby both, the immediate problem would be corrected and the normal physiological processes restored, without any need for subsequent drugs. However, conflicting ethical controversies surround this new medicine approach, inside and outside the medical community, especially when human embryonic stem cells (h-ESCs) are concerned. This ethical debate on clinical use of h-ESCs has recently encouraged the research on "adult" stem cells (ASCs) regarded as a less conflicting alternative for the future of regenerative medicine.


Efficacy of antiseptic mouthrinses against SARS-CoV-2: A prospective randomized placebo-controlled pilot study.
Coronavirus-disease-19 (COVID-19) continues to affect millions of individuals worldwide. Antiviral activity of mouthrinses remains an important research area as the oral cavity is a site of SARS-CoV-2 initial replication. The aim of this study was to assess the effectiveness of three different mouthrinses in reducing the oral/oropharyngeal SARS-CoV-2 viral load. Adult patients, hospitalized with confirmed COVID-19 were recruited for the study. Oral/oropharyngeal baseline SARS-CoV-2 samples were collected and analyzed by Real-Time-PCR. Subsequently, patients were instructed to rinse with 1 % hydrogen peroxide (H2O2), 0.12 % chlorhexidine (CHX), 1 % povidone‑iodine (PVP-I) or Sodium Chloride 0.9 % (placebo). Viral loads were measured right after (T1), and at 45 min (T2) from the rinse. In the PVP-I 1 % group, 5/8 (62.5 %) patients at T1, and 3/8 (37.5 %) patients at T2, SARS-CoV-2 was not detectable in the swab specimens. In the H2O2 1 % group, 2/11 (18.2 %) patients at T1, and 2/11 (18.2 %) other patients at T2 showed no SARS-CoV-2 loads. One (12.5 %) patient in the CHX 0.12 % group showed SARS-CoV-2 negativity at T2. One (9.1 %) patient at T1, and another (9.1 %) patient at T2 showed no SARS-CoV-2 loads in the placebo group. Oral SARS-CoV-2 loads were reduced at T1 in the PVP-I 1 % and H2O2 1 % groups. PVP-I 1 % was the most effective rinse especially in patients with low viral copy numbers at baseline.


Induction of conditioned avoidance via mental imagery.
There is a growing interest on how mental imagery may be involved in the onset and maintenance of anxiety-related disorders. Here, we used an experimental design to investigate whether a key symptom across anxiety-related disorders, namely avoidance, can be induced via mental imagery. Healthy participants first learned that one neutral stimulus (A) was associated with a mild electric shock and two other neutral stimuli (B and C) were not. They then learned to cancel the shock when A was presented, by pressing a button on a keyboard ('behavioral avoidance'). Next, they were asked to imagine that stimulus B was followed by the shock (i.e., without actual B or shock presentations; Experiment 1; N = 66) or they were shown B and asked to imagine the shock (i.e., without actual shock presentations; Experiment 2; N = 60). Finally, in the test phase, they were shown each of the three stimuli (without the shock) and given the opportunity to make the avoidance response. Results showed that participants tended to avoid B in the test phase in Experiment 1, even though it had never been presented with the shock but not in Experiment 2. We discuss how the findings may explain the acquisition of avoidance in the presentation of innocuousstimuli across anxiety-related disorders.


Genome-wide functional analysis of hot pepper immune receptors reveals an autonomous NLR clade in seed plants.
Plants possess hundreds of intracellular immune receptors encoding nucleotide-binding domain leucine-rich repeat (NLR) proteins. Full-length NLRs or a specific domain of NLRs often induce plant cell death in the absence of pathogen infection. In this study we used genome-wide transient expression analysis to identify a group of NLRs (ANLs; ancient and autonomous NLRs) carrying autoactive coiled-coil (CCA ) domains in pepper (Capsicum annuum). CCA -mediated cell death mimics hypersensitive cell death triggered by the interaction between NLRs and pathogen effectors. Sequence alignment and mutagenesis analyses revealed that the intact α1 helix of CCA s is critical for both CCA - and ANL-mediated cell death. Cell death induced by CCA s does not require NRG1/ADR1 or NRC type helper NLRs, suggesting ANLs may function as singleton NLRs. We also found that CCA s localize to the plasma membrane, as demonstrated for Arabidopsis singleton NLR ZAR1. Extended studies revealed that autoactive CCA s are well conserved in other Solanaceae plants as well as in rice, a monocot plant. Further phylogenetic analyses revealed that ANLs are present in all tested seed plants (spermatophytes). Our study not only uncovers the autonomous NLR clade in plants but also provides powerful resources for dissecting the underlying molecular mechanism of NLR-mediated cell death in plants.


Resident cardiomyocyte precursor stem cells in the myocardium of infants of the first two years of life with tetralogy of Fallot.
We studied the content of resident myocardial stem cells, cardiomyocyte precursors, in myocardial biopsy specimens from the right ventricular outflow tract of patients of the first two years of life with tetralogy of Fallot. Myocardial resident stem cells were detected by the method of confocal immunohistochemistry using antibodies to c-kit and sarcomeric α-actin. The diameter of right ventricular cardiomyocytes was measured; the presence of myolysis zones was semiquantitatively evaluated. Electron microscopic analysis of right ventricular cardiomyocytes was performed. The data on the content of resident myocardial stem cells were compared with clinical and functional parameters of the patients and morphological peculiarities of the myocardium. C-kit-positive resident myocardial stem cells were detected in the right ventricle of 17.4% patients with tetralogy of Fallot. The content of resident myocardial stem cells in these patients varied from 4 to 45 (median 11) per 1 mln cardiomyocytes; this parameter was higher in patients with high content of small cardiomyocytes (diameter <10 μ) and cardiomyocytes with incomplete myofibril assembly in the right ventricular myocardium.


Childhood trauma in alcoholics.
Many studies have been conducted to evaluate the relationship between childhood trauma and alcoholism. In this study 80 alcoholics were chosen according to their hospitalization order. The control group consisted of 60 subjects, with no history of alcohol use, matched with the patient group in age and sex. A sociodemographic and clinical data form, a questionnaire focusing on traumatic life experiences in childhood and The Childhood Trauma Questionnaire, Hamilton Depression Rating Scale, and Hamilton Anxiety Rating Scale were applied to both groups. Significant differences were found between the two groups on traumatic life experiences in childhood. Results suggested that childhood trauma positively correlates with anxiety and affective symptoms among alcoholics. Further studies are needed concerning this issue.


Postpartum depression and its association with intimate partner violence and inadequate social support in Ethiopia: a systematic review and meta-analysis.
Despite remarkable progress in the reduction of maternal mortality, postpartum depression remains a major public health problem among vulnerable populations. In Ethiopia, study findings regarding postpartum depression and its association with intimate partner violence and social support have been inconsistent. Therefore, this systematic review and meta-analysis estimate the pooled prevalence of postpartum depression and its association with intimate partner violence and inadequate social support in Ethiopia. We systematically searched international databases like PubMed, Web of Science, SCOPUS, CINAHL, PsycINFO, Google Scholar, Science Direct, and the Cochrane Library. All identified observational studies reporting the postpartum depression and or its predictors in Ethiopia were included. Two authors independently extracted all necessary data using a standardized data extraction format. The I2 statistics were used to assess the heterogeneity of the studies. A random-effects model was computed to estimate the pooled prevalence of postpartum depression and its associations with the selected predictors. The random effect meta-analysis of thirteen studies showed a pooled prevalence of postpartum depression was 21.55% (95% CI: 17.89, 25.94). The highest prevalence of postpartum depression occurred in Addis Ababa, 23.3% and the lowest was in Harar, 13.11%. Our meta-analysis indicated a 5.46 folds increased risk of postpartum depression among women exposed to intimate partner violence (POR = 5.46 (95%CI: 3.94, 7.56, I2=38.8%) and 6.27 folds increased risk postpartum depression among women who had inadequate social support (POR = 6.27 (95%CI: 4.83, 8.13, I2=0) relative to those who had adequate social support. The meta-analysis further revealed that marital dissatisfaction (POR = 2.6%; 95%CI: 1.48-4.65), previous postpartum depression (POR = 2.03%; 95%CI: 1.72-2.4), and substance abuse (POR = 2.03%; 95%CI: 1.72-2.4) were associated with postpartum depression. Our study indicates that two in every ten postpartum women in Ethiopia are suffering from postpartum depression. Intimate partner violence and social support should be a major focus to improve women's mental health during postpartum period with the reduction of substance abuse. There is an urgent need for concerted efforts in the reduction of postpartum depression through prevention efforts of intimate partner violence and substance abuse.


Progression of fibrosis in liver transplant recipients with hepatitis C before and after sustained virologic response.
Liver transplant (LT) recipients with untreated hepatitis C (HCV) are at risk for cirrhosis graft failure. The advent of direct acting antiviral agents (DAA) has improved outcomes in HCV. We aim to examine liver transplant outcomes and allograft fibrosis development/progression after sustained virologic response (SVR). We performed a retrospective cohort study of 226 consecutive liver transplant recipients with HCV from 2007 to 2018. The cohort was split into transplants pre (Group A) and post (Group B) 2014 to reflect the introduction of DAAs. Fibrosis was monitored with liver biopsy and non-invasive imaging. Group B had significantly improved HCV treatment rates and earlier SVR compared to Group A, with a cumulative incidence rate of SVR at 2 years of 86.7% versus 15.4% (HR = .11, p < .001). Prior to achieving SVR, Group A demonstrated worsening of fibrosis stage per year (+.21, p < .001) whereas Group B showed minimal change on protocol annual biopsy (-.02, p = .80). After SVR, most patients were followed non-invasively and demonstrated stable or improved fibrosis stage over time. Patients undergoing transient elastography showed regression in fibrosis stage per year (-.19, p < .001). HCV patients undergoing LT after 2014 had higher rates of SVR and improved clinically relevant transplant outcomes, namely less graft loss and death relating to HCV. Fibrosis progression halted or improved after SVR in both cohorts, suggesting that LT recipients with SVR do not require fibrosis monitoring even with established fibrosis prior to SVR.


Involvement of protein kinase C in the interleukin 1 alpha-induced gene expression of matrix metalloproteinases and tissue inhibitor-1 of metalloproteinases (TIMP-1) in human uterine cervical fibroblasts.
The role of protein kinase C in the interleukin 1 (IL-1)-mediated production of pro-matrix metalloproteinases (proMMPs) and tissue inhibitor-1 of metalloproteinases (TIMP-1) in human uterine cervical fibro-blasts has been investigated. IL-1 and a protein kinase C activator, 12-O-tetradecanoylphorbol 13-acetate (TPA) augmented the production of proMMP-1 (interstitial procollagenase), proMMP-3 (prostromelysin-1) and TIMP-1, but their effects were inhibited by the protein kinase C inhibitors 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride (H-7) and staurosporine in a dose-dependent manner. The suppressive effect of H-7 and staurosporine on the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 resulted from the decrease in the steady-state levels of their mRNAs. When protein kinase C was down-regulated by treating the cells with a high level of TPA, the inductive effect of IL-1 upon proMMP-3 production was reduced considerably. These results indicate that protein kinase C mediates the IL-1-induced production of proMMPs-1 and -3 and TIMP-1 at the pretranslational level in human uterine cervical fibroblasts. On the other hand, neither IL-1 nor TPA modulated the production of proMMP-2 (progelatinase A). Both IL-1 and TPA also accelerated the production of prostaglandin E2 (PGE2) by cervical fibroblasts. However, the treatment of the cells with staurosporine in the presence of IL-1 or TPA further augmented PGE2 synthesis, suggesting that the increased synthesis of PGE2 by IL-1 treatment is mediated via signalling pathways distinct from those of proMMPs-1 and -3 and TIMP-1.


[Production and application of rabbit anti-imitative spider dragline silk protein polyclonal antibody].
A synthetic spider dragline gene s600 was cloned into fusion protein expression vector pGEX-KG and expressed in Escherichia coli. Protein S600 was purified and rabbit antiserum was prepared. Amino acid composition analysis confirmed the right expression of S600. Western blot analysis revealed that anti-S600 antiserum could react with natural spider silk, so the synthetic dragline protein, designed by the authors, shares similar immunological characteristics with the natural spider silk. An ELISA system was also established for the quantitative detection of synthetic dragline protein expression in silk gland (or in the cocoon) of transgenic silkworm.


Synthesis of alkylated potato starch derivatives and their potential in the aqueous solubilization of benzo[a]pyrene.
For the development of renewable bioproducts able to solubilize organic persistent pollutant such as benzo[a]pyrene (BaP), modified potato starch was synthesized by alkylation. The addition of alkyl chains was performed with three different alkylation agents: epoxyalkane, alkenyl succinic anhydride and 1,4-butane sultone. Twelve alkylated starches were obtained with different molar substitutions (MS) and various alkyl chain lengths (to three carbons up to sixteen). The chemical structural characteristics were investigated by methods of (1)H NMR and FTIR. In comparison with the native starch, the ether modified starches showed in general an enhancement of their aqueous solubility whereas the ester modified starches stimulated the BaP aqueous solubilization. Indeed, the compounds P6 and P12, which increased 40-fold the BaP aqueous concentration, present high surfactant properties.


Opiates inhibit pedunculopontine neurones in guinea pig brainstem slices.
Intracellular recordings were obtained from pedunculopontine neurones in guinea-pig brainstem slices. These cells were characterized by a broad action potential, an A-like conductance and fired spontaneously in a regular manner. These neurones were inhibited by bath-application of both carbachol and serotonine at concentrations of 10(-4) M. Opioid peptides induced a dose-dependent hyperpolarization and a reduction in the spontaneous firing. These latter effects could be blocked by the opiate antagonist naloxone and were direct as they persisted in presence of tetrodotoxine or high magnesium/low calcium-containing salines. They were mediated by an opiate receptor of the mu type since they were obtained with the mu-preferring enkephalin analogues FK 33-824 and DAGO, but neither with the delta nor the kappa analogues such as DPLPE or U-50,488.


Maternal Flaxseed Oil During Lactation Enhances Bone Development in Male Rat Pups.
Flaxseed oil is an alpha linolenic acid source important in the growth and body development stage; furthermore, this acid acts on adipose tissue and bone health. The aim of this study was to evaluate body composition, fatty acid composition, hormone profile, retroperitoneal adipocyte area and femur structure of pups at weaning, whose mothers were fed a diet containing flaxseed oil during lactation. After birth, pups were randomly assigned: control (C, n = 12) and flaxseed oil (FO, n = 12), rats whose mothers were treated with diet containing soybean or flaxseed oil. At 21 days, the pups were weaned and body mass, length, body composition, biochemical parameter, leptin, osteoprotegerin, osteocalcin, fatty acids composition, intra-abdominal fat mass and femur structure were analyzed. FO showed (p < 0.05): higher body mass (+12 %) and length (+9 %); body fat mass (g, +45 %); bone mineral density (+8 %), bone mineral content (+55 %) and bone area (+35 %), osteocalcin (+173 %) and osteoprotegerin (+183 %). Arachidonic acid was lower (p < 0.0001), alpha-linolenic and eicosapentaenoic were higher (p < 0.0001). Intra-abdominal fat mass was higher (+25 %), however, the retroperitoneal adipocytes area was lower (-44 %). Femur mass (+10 %), distance between epiphyses (+4 %) and bone mineral density (+13 %) were higher. The study demonstrates that adequate flaxseed oil content during a lactation diet plays an important role in the development of pups.


Development and optimisation of a high-performance liquid chromatographic assay for tioconazole and its potential impurities. Part II. Selection of detection conditions for potential impurities.
An optimised high-performance liquid chromatographic separation developed for the assay of tioconazole and its potential impurities has been applied to real-world samples where tioconazole is in excess. As severe peak tailing interferes with the assay of two of the impurity peaks, changes in detection wavelength have been examined as a means to discriminate between this interference. The resulting enhancement of resolution has been exploited in the optimisation of analysis time.


Methemoglobin in hypoxic rats.
Methemoglobin levels have been found to vary with altitude and to shift the hemoglobin-oxygen dissociation curve. In this study, hematocrits and methemoglobin levels were monitored in rats exposed to hypoxia (420 torr absolute) for various intervals. Hematocrits gradually increased throughout the period of hypoxia, while methemoglobin levels rose by 12 h, peaked at 24 h and returned to control level by day 6. These data, in the context of other work, suggest that increased methemoglobin is important in acclimation to hypoxia.


STAP-2 interacts with and modulates BCR-ABL-mediated tumorigenesis.
In chronic myeloid leukemia (CML), the BCR-ABL fusion oncoprotein activates multiple pathways involved in cell survival, growth promotion and disease progression. In this report, we show that the signal-transducing adaptor protein-2 (STAP-2) is involved in BCR-ABL activity. We demonstrate that STAP-2 bound to BCR-ABL, and BCR and ABL proteins, depending on the STAP-2 Src homology 2-like domain. BCR-ABL phosphorylates STAP-2 Tyr250 and the phosphorylated STAP-2 in turn upregulated BCR-ABL phosphorylation, leading to enhanced activation of downstream signaling molecules including ERK (extracellular-signal-regulated kinase), STAT5 (signal transducer and activator of transcription 5), BCL-xL (B-cell lymphoma-extra large) and BCL-2(B-cell lymphoma 2). In addition, STAP-2 interacts with BCR-ABL to alter chemokine receptor expression leading to downregulation of CXCR4 and upregulation of CCR7. The interaction between STAP-2 and BCR-ABL plays a crucial role in conferring a growth advantage and resistance to imatinib, a BCR-ABL inhibitor, as well as tumor progression. Notably, mice injected with BCR-ABL/STAP-2-expressing Ba/F3 cells developed lymph node enlargement and hepatosplenomegaly. Moreover, suppression of STAP-2 in K562 CML cells resulted in no tumor formation in mice. Our results demonstrate a critical contribution of STAP-2 in BCR-ABL activity, and suggest that STAP-2 might be an important candidate for drug development for patients with CML. Furthermore, the expression of STAP-2 provides useful information for estimating the characteristics of individual CML clones.


Why Have Two When One Will Do? Comparing Task Representations across Amygdala and Prefrontal Cortex in Single Neurons and Neuronal Populations.
Many brain areas represent aspects of learned behavior. How do representations differ between regions? In this issue of Neuron, Kyriazi et al. (2020) show how the amygdala and prefrontal cortex use distinct strategies to code features of a complex task.


The effects of mifepristone on the expressions of osteopontin, interleukin-6 and leukemia inhibitory factor in the villi of early pregnant women.
The autocrine, paracrine and hormonal effects of osteopontin (OPN), leukemia inhibitory factor (LIF) and interleukin-6 (IL-6) suggest that these cytokines may play key roles at the maternal-fetal interface. This study was performed to determine the effects of mifepristone on OPN, LIF and IL-6 mRNA and protein expressions in the villi in early pregnancy. Twenty-nine healthy women seeking termination of pregnancy up to 40 days' gestation were recruited. The study group (n=14) was given 150 mg mifepristone 24 h before vacuum aspiration. The control group (n=15) was not given any treatment prior to vacuum aspiration. Villi were collected, and immunohistochemical analysis and real-time reverse transcription PCR (RT-PCR) were used to detect the locations and the expression levels of OPN, IL-6 and LIF mRNA. In the study group, the expression level of OPN protein in the villous trophoblast and stoma cells was significantly lower (p<.01), while the expression levels of IL-6 and LIF protein were significantly higher than those in the control group (p<.01, p<.05, respectively). Compared with the control group, the relative expression of OPN mRNA was significantly lower (p=.001) and the IL-6 and LIF mRNA expression levels were significantly higher in the study group (p=.003 and p<.001, respectively). OPN, IL-6 and LIF may have critical roles in human pregnancy maintenance. These three factors may be involved in the immunological reaction initiated by mifepristone.


Extracting a stimulus-unlocked component from EEG during NoGo trials of a Go/NoGo task.
Like electroencephalographic (EEG) activity during reaction time tasks, EEG activity during tasks without overt responses may also consist of two components: stimulus-locked and -unlocked components. The extraction of such stimulus-unlocked components has been difficult owing to the unknown delays. Here, we propose a novel method to extract both of the two components from single-channel EEG epochs. In this method, we initially set random values for the delays and extract uncontaminated stimulus-locked and -unlocked components using the preset delays and a discrete Fourier transform. Then, we reconstruct the EEG by overlapping the extracted components with the preset delays, and calculate the residual errors between the reconstructed and original EEG. This procedure is repeated by updating the delays until the residual errors become adequately small. After verifying the performance of this method by two kinds of simulations with artificial and EEG data, we apply the method to EEG during NoGo trials of a Go/NoGo task, and obtain the stimulus-unlocked components, the magnitudes of which are comparable with those of the stimulus-locked components. By applying this method, it is possible to study internal and subjective brain activity, which occurs with variable delays.


Ambulatory Electrocardiography Monitoring for Early Discharge After Minimally Invasive Valve Surgery.
We sought to compare outcomes after early discharge in patients with and without predischarge diagnosis of arrhythmia following minimally invasive valve surgery (MIVS). We retrospectively reviewed ambulatory electrocardiography (AECG) datasheets and medical records of patients discharged with 14-d AECG monitoring from our facility between October 2019 and March 2022 ≤ 3 d after MIVS. Baseline and clinical characteristics, arrhythmias during AECG monitoring, and 30-d adverse outcomes were reported for the population and stratified by presence or absence of predischarge arrhythmia. Of 41 patients discharged ≤3 d postoperatively of MIVS, 17 (41.5%) experienced predischarge arrhythmias and 24 (58.5%) did not. The population was predominantly male and White with a median age of 62 y [57, 70]. Baseline and clinical characteristics did not differ between subgroups. Most patients (92.7% [n = 38]) experienced one or more tachyarrhythmias during the AECG monitoring period. There were similar proportions of patients experiencing atrial fibrillation in both groups, but patients with predischarge arrhythmias had higher burden of atrial fibrillation on AECG monitoring (27.60% [6.57%, 100%] versus 1.65% [0.76%, 4.32%]; P = 0.004). The predischarge arrhythmia subgroup had higher proportions of patients experiencing nonsustained ventricular tachycardia but lower proportions experiencing supraventricular tachycardia. There were no mortalities within 30 d of surgery. Six (14.6%) patients were readmitted within 30 d with equal proportions of readmissions between subgroups (P = 0.662). Early discharge timelines and noninvasive monitoring techniques can allow patients to return to their normal activities quicker in the comfort of their own home with no increased risk of morbidity or mortality.


Morphine self-administration and EEG power spectra in the rat.
Power spectral analyses were used to study changes in cortical EEG during morphine self-administration in freely-moving dependent rats prepared with chronic cortical and muscle electrodes and with permanent indwelling IV cannulae. As time progressed from a morphine self-injection toward another injection, a significant spectral shift of the EEG to lower frequencies occurred during successive REM sleep episodes. Each morphine self-injection reinstated the predominance of higher frequencies in the EEG spectra. These EEG changes which preceded lever pressing may reflect changes in morphine plasma levels and in the state of the CNS that precede drug-seeking behavior.


Oncological and perioperative outcomes of surgery with or without metastasis-directed therapy as part of a multimodal treatment in men with de-novo oligometastatic prostate cancer.
To investigate the feasibility, safety, and oncological outcomes of Radical Prostatectomy (RP; either Robot-Assisted [RARP] or Open RP [ORP]) in oligometastatic prostate cancer (omPCa). Additionally, we assessed whether there was an added benefit of metastasis-directed therapy (MDT) in these patients in the adjuvant setting. Overall, 68 patients with omPCa (≤ 5 skeletal lesions at conventional imaging) treated with RP and pelvic lymph node dissection between 2006 and 2022 were included. Additional therapies (androgen deprivation therapy [ADT] and MDT) were administered according to the treating physicians' judgment. MDT was defined as metastasis surgery/radiotherapy within 6 months of RP. We assessed Clinical Progression (CP), Biochemical Recurrence (BCR), post-operative complications and overall mortality (OM) of RP and the impact of adjuvant MDT + ADT versus RP + ADT alone. Median follow-up was 73 months (IQR 62-89). RARP reduced the risk of severe complications after adjusting for age and CCI (OR 0.15; p = 0.02). After RP, 68% patients were continent. Median 90-days PSA after RP was 0.12 ng/dL. CP and OM-free survival at 7 years were 50% and 79%, respectively. The 7-years OM-free survival rates were 93 vs. 75% for men treated with vs. without MDT (p = 0.04). At regression analyses, MDT after surgery was associated with a 70% decreased mortality rate (HR 0.27, p = 0.04). RP appeared to represent a safe and feasible option in omPCa. RARP reduced the risk of severe complications. Integrating MDT with surgery in the context of a multimodal treatment might improve survival in selected omPCa patients.


Placental-ovarian relationship in the control of testosterone secretion in the rat.
Both ovaries and placentae of rats produce androgen in the second half of pregnancy. The objectives of this investigation were to determine whether the pituitary controls both ovarian and placental secretion of testosterone, to find out whether ovarian secretion of testosterone is maintained by the placenta, and to examine whether levels of testosterone produced by the ovaries and placentae depend upon the number of placentae present. Pregnant rats were hypophysectomized with or without hysterectomy in one experiment, and hypophysectomized with or without partial hysterectomy leaving one placenta in situ in another experiment. Testosterone output by the placenta(e) or the ovary was quantified. The results suggest that placental secretion of testosterone is independent of the pituitary between days 12 and 18 of pregnancy, reduction in placental number causes the remaining placenta to compensate by increasing its testosterone output, and ovarian secretion of testosterone may be under placental control between days 12 and 18 of pregnancy.


Uncommon properties of pLD105 conjugative plasmid.
Plasmid pLD105 isolated from a clinical strain of E. coli determines nitrofuran resistance due to inactivation of low-molecular-weight nitrofuran reductase subunit. pLD105 plasmid belongs to IncF. It is a conjugative plasmid and mobilizes chromosome markers, but is not transmitted to strains containing other plasmids. However, the presence of pLD105 plasmid in the recipient strain does not prevent incorporation of other plasmids, including nonconjugative ones. Transfer of nonconjugative plasmids from the donor to a recipient strain carrying pLD105 was denoted as "reverse donation".


Early cognitive status and productivity outcome after traumatic brain injury: findings from the TBI model systems.
To evaluate the contribution of early cognitive assessment to the prediction of productivity outcome after traumatic brain injury (TBI) adjusted for severity of injury, demographic factors, and preinjury employment status. Inception cohort. Six inpatient brain injury rehabilitation programs. A total of 388 adults with TBI whose posttraumatic amnesia (PTA) resolved before discharge from inpatient rehabilitation. Administered neuropsychologic tests during inpatient stay on emergence from PTA. Follow-up interview and evaluation. Predictor measures also determined. Productivity status at follow-up 12 months postinjury. Multiple logistic regression analysis revealed that preinjury productivity status, duration of PTA, education level, and early cognitive status each made significant, independent contributions to the prediction of productivity status at follow-up. When adjusted for all other predictors, persons scoring at the 75th percentile on early cognitive status (less impaired) had 1.61 times greater odds (95% confidence interval [CI], 1.07-2.41) of being productive follow-up than those scoring at the 25th percentile (more impaired). Without adjustment, persons scoring at the 75th percentile had 2.46 times greater odds (95% CI, 1.77-3.43) of being productive at follow-up. Findings support the utility of early cognitive assessment by using neuropsychologic tests. In addition to other benefits, early cognitive assessment makes an independent contribution to prediction of late outcome. Findings support the clinical practice of performing initial neuropsychologic evaluations after resolution of PTA.


Biomineralized biomimetic organic/inorganic hybrid hydrogels based on hyaluronic acid and poloxamer.
A biomineralized hydrogel system containing hyaluronic acid (HA) and poloxamer composed of a poly(ethylene oxide)/poly(propylene oxide)/poly(ethylene oxide) (PEO-PPO-PEO) block copolymer was developed as a biomimetic thermo-responsive injectable hydrogel system for bone regeneration. Using HA and poloxamer macromers with polymerizable residues, organic/inorganic HA/poloxamer hydrogels with various compositions were prepared and subjected to a biomineralization process to mimic the bone extracellular matrix. An increase in HA content within the hydrogels enhanced intermolecular chelation with calcium ions, leading to an increase in nucleation and growth of calcium phosphate in the hydrogels. After the biomineralization procedure, a crystalline formation was observed within and on the surface of the hydrogel. All of the HA/poloxamer hydrogel samples exhibited relatively high water content of greater than 90% at 25 °C, and the water content was influenced by the HA/poloxamer composition, biomineralization, and temperature. In particular, the HA/poloxamer hydrogel was injectable through a syringe without demonstrating appreciable macroscopic fracture at room temperature, whereas it was more opaque and adopted a more rigid structure as the temperature increased because of the increasing hydrophobicity of poloxamer. The enzymatic degradation behavior of the hydrogels depended on the concentration of hyaluronidase, HA/poloxamer composition, and biomineralization. The release kinetics of model drugs from HA/poloxamer hydrogels was primarily dependent on the drug loading content, water content, biomineralization of the hydrogels, and ionic properties of the drug. These results indicate that biomineralized HA/poloxamer hydrogel is a promising candidate material for a biomimetic hydrogel system that promotes bone tissue repair and regeneration via local delivery of drugs.


[Preoperative weight loss in bariatric surgery candidate patients. evidence-based recommendations].
Bariatric surgery is becoming increasingly more common in the treatment of morbid obesity in our hospitals. One of the measures being used to optimise the results of this surgery seems to be the standardising the preoperative weight loss. As there are no universal recommendations for carrying out this weight loss, a review of this topic is presented. To analyse whether sufficient scientific evidence exists to recommend preoperative weight loss in candidate patients for bariatric surgery. What would be the best options to carry out this weight loss is also analysed, as well as making some recommendations based on the scientific evidence. There is great heterogeneity in the designs of the different studies, with different guidelines for weight loss and various surgical techniques. However, preoperative weight loss leads to a decrease in the size of the liver and intra-abdominal fat, which improves the surgical field and intra-operative view, which in turn helps during the surgical act, both in open as well as laparoscopic surgery. There is no consensus on the effect of preoperative weight loss has in predicting the medium or long term results after bariatric surgery. The current scientific evidence makes preoperative weight loss recommendable in candidate patients for bariatric surgery. However, there is no consensus on what is the best procedure to achieve this preoperative weight loss.


Analytical strategies for the screening of veterinary drugs and their residues in edible products.
The development of analytical strategies for the regulatory control of drug residues in food-producing animals is discussed. Analytical methods for the determination of veterinary drugs in edible products are based on microbiological, immunochemical and physicochemical principles. Because of complexity of biological matrices such as egg, milk and meat, well designed, and often sophisticated, off-line or on-line sample treatment procedures are essential, especially when utilising physicochemical multi-residue screening procedures. Since large series of samples have often to be analysed, automation is increasingly becoming important. Confirmation of the identity of drug residues and validation of the analytical results implies the use of adequate analytical methods. In its turn, this requires well established criteria for those methods and/or equivalent reference methods.


Anatomic Eponyms in Neuroradiology: Head and Neck.
In medicine, an eponym is a word-typically referring to an anatomic structure, disease, or syndrome-that is derived from a person's name. Medical eponyms are ubiquitous and numerous. They are also at times controversial. Eponyms reflect medicine's rich and colorful history and can be useful for concisely conveying complex concepts. Familiarity with eponyms facilitates correct usage and accurate communication. In this article, 22 eponyms used to describe anatomic structures of the head and neck are discussed. For each structure, the author first provides a biographical account of the individual for whom the structure is named. An anatomic description and brief discussion of the structure's clinical relevance follow.


Overlay technique for direct detection and identification of haemolytic Listeria on selective plating medium. Comparison of five media.
An overlay technique is proposed for the identification and counting of haemolytic Listeria colonies directly on selective plating media. The technique was applied to different Listeria-selective plating media. In pure culture studies with collection strains, the overlay technique was more efficient and reliable for detection haemolytic Listeria species compared with the incorporation of blood into the agar. The efficacy of the overlay technique for the direct detection of haemolytic colonies of Listeria from raw milk samples was related to agar selectivity. The best results were obtained with Listeria-selective agar medium modified (LSAMM). Catalase assay, together with reactions for aesculin and tellurite, were useful and reliable criteria for the identification of Listeria. All colonies on LSAMM which were positive for catalase, tellurite and aesculin while those displaying typical haemolysis corresponded in most cases to L. monocytogenes.


Protein restriction impairs the response activation/responsivity of MAPK signaling pathway of hematopoietic stem cells.
Protein restriction (PR) leads to bone marrow hypoplasia with changes in stromal cellularity components of the extracellular matrix in hematopoietic stem cells (HSCs). However, the underlying signaling mechanisms are poorly understood. We hypothesize that PR impairs the HSC mitogen-activated protein kinase (MAPK) signaling pathway response activation. Our aim is to evaluate the activation of MAPK and interleukin-3 (IL-3) proteins in HSC to explain PR-induced bone marrow hypoplasia, which causes altered proliferation and differentiation. C57BL/6 male mice were subjected to a low-protein diet (2% protein) or normoproteic (12% protein). PKC, PLCγ2, CaMKII, AKT, STAT3/5, ERK1/2, JNK, and p38d phosphorylation were evaluated by flow cytometry, and GATA1/2, PU.1, C/EBPα, NF-E2, and Ikz-3 genes (mRNAs) assessed by quantitative real-time-polymerase chain reaction. Pathway proteins, such as PLCγ2, JAK2, STAT3/5, PKC, and RAS do not respond to the IL-3 stimulus in PR, leading to lower activation of ERK1/2 and Ca2+ signaling pathways, consequently lowering the production of hematopoietic transcription factors. Colony forming units granulocyte-macrophage and colony forming units macrophage formation are impaired in PR even after being stimulated with IL-3. Long-term hematopoietic stem cells, short-term hematopoietic stem cells, granulocyte myeloid progenitor, and megakaryocyte-erythroid progenitor cells were significantly reduced in PR animals. This study shows for the first time that activation of MAPK pathway key proteins in HSCs is impaired in cases of PR. Several pathway proteins, such as PLCγ2, JAK2, STAT3, PKC, and RAS do not respond to IL-3 stimulation, leading to lower activation of extracellular signal-regulated protein kinase 1/2 and consequently lower production of hematopoietic transcription factors GATA1/2, PU.1, C/EBPa, NF-E2, and Ikz3. These changes result in a reduction in colony-forming units, proliferation, and differentiation, leading to hypocellularity.


Computation of a three dimensional image of a periodic specimen from a single view of an oblique section.
We describe here a method for computing a three dimensional map of a periodic specimen from a single electron micrograph of an obliquely cut section. Neighbouring areas of such an image display successively the contents of the unit cell of the structure. The reconstruction procedure can be considered in two steps. The first step involves restacking of successive areas to produce an image akin to that produced by serial section reconstruction. The resolution normal to the section would, at this stage, be limited by the thickness of the section, since the micrograph represents a projection of the density in the section. However, because of the periodic nature of the specimen, the image contains redundant information, which can be used in an attempt to deconvolute the section thickness and thus produce improved resolution normal to the section. The computation can be carried out directly with the densities or more conveniently, particularly for three dimensional crystals, by using Fourier transforms. The approach, which is most powerful when the section is thin, is insensitive to the collapse of the section caused by electron irradiation. Striated muscle provides particularly suitable specimens for such analysis and we present, as examples, computed maps of the M-band of fish muscle and of insect flight muscle in rigor.


GENOCOP Algorithm and Hierarchical Grid Transformation for Image Warping of Two-Dimensional Gel Electrophoretic Maps.
Hierarchical grid transformation is a powerful hierarchical approach to 2-D map warping, able to model both global and local deformations. The algorithm can be stopped when a desired degree of accuracy in the images alignment is obtained. The deformed image is warped and aligned to the target image using a grid where the number of nodes increases in each step of the algorithm. The numerical optimization of the position of the nodes of the grid can be efficiently solved by genetic algorithms, ensuring the achievement of the optimal position of the nodes with a low computational cost with respect to other methods. Here, the optimization of the position of the nodes is carried out by GENOCOP (genetic algorithm for numerical optimization of constrained problems), refined by the following conjugate gradient optimization step. The modeling of the warped space is then achieved by a spline model where some constraints are introduced in the choice of the nodes that are moved. The whole procedure can be intended as an evolutionary method that models the deformation of the gel map at different levels of detail.


Superselective intraarterial cerebral infusion of cetuximab after osmotic blood/brain barrier disruption for recurrent malignant glioma: phase I study.
Objective To establish a maximum tolerated dose of superselective intraarterial cerebral infusion (SIACI) of Cetuximab after osmotic disruption of the blood-brain barrier (BBB) with mannitol, and examine safety of the procedure in patients with recurrent malignant glioma. Methods A total of 15 patients with recurrent malignant glioma were included in the current study. The starting dose of Cetuximab was 100 mg/m(2) and dose escalation was done to 250 mg/m(2). All patients were observed for 28 days post-infusion for any side effects. Results There was no dose-limiting toxicity from a single dose of SIACI of Cetuximab up to 250 mg/m(2) after osmotic BBB disruption with mannitol. A tolerable rash was seen in 2 patients, anaphylaxis in 1 patient, isolated seizure in 1 patient, and seizure and cerebral edema in 1 patient. Discussion SIACI of mannitol followed by Cetuximab (up to 250 mg/m(2)) for recurrent malignant glioma is safe and well tolerated. A Phase I/II trial is currently underway to determine the efficacy of SIACI of cetuximab in patients with high-grade glioma.


The pros and cons of probiotics.
Research into the human microbiome has encouraged proliferation of probiotic foods and supplements. Although the health claims seem legit, Carrie Arnold finds not everyone is convinced.