Inherited DNA Repair Defects Disrupt the Structure and Function of Human Skin.
Squamous cell carcinoma (SCC) is a global public health burden originating in epidermal stem and progenitor cells (ESPCs) of the skin and mucosa. To understand how genetic risk factors contribute to SCC, studies of ESPC biology are imperative. Children with Fanconi anemia (FA) are a paradigm for extreme SCC susceptibility caused by germline loss-of-function mutations in FA DNA repair pathway genes. To discover epidermal vulnerabilities, patient-derived pluripotent stem cells (PSCs) conditional for the FA pathway were differentiated into ESPCs and PSC-derived epidermal organotypic rafts (PSC-EORs). FA PSC-EORs harbored diminished cell-cell junctions and increased proliferation in the basal cell compartment. Furthermore, desmosome and hemidesmosome defects were identified in the skin of FA patients, and these translated into accelerated blistering following mechanically induced stress. Together, we demonstrate that a critical DNA repair pathway maintains the structure and function of human skin and provide 3D epidermal models wherein SCC prevention can now be explored.


Longitudinal quantitation of middle cerebral artery blood flow in normal human fetuses.
We attempted to quantify noninvasively blood flow of the middle cerebral artery in human fetuses during five distinct periods. Twenty normal fetuses had color pulsed Doppler ultrasonography of the middle cerebral artery. A total of 68 studies were successfully done and are reported. The Doppler sample was placed as parallel to the direction of the vessel flow as possible. All waveforms were recorded on a strip chart at a preset speed of 100 mm/sec. Six Doppler waveforms were digitized for the time velocity integral (area under the curve is equal to time velocity integral) and averaged. Middle cerebral blood flow was obtained by multiplying the time velocity integral of the Doppler curve by the cross-sectional area of the vessel. The combined cardiac output was obtained by adding the right and left ventricular outputs, which were obtained by multiplying the time velocity integrals by the area of the corresponding annuli. Analysis of variance for repeated measurements was used to determine significance. The diameter of the middle cerebral artery, the time velocity integral, and the peak flow velocity of the Doppler waveform increased significantly with advancing gestational age. Blood flow to the middle cerebral artery ranged from 23 ml/min at 19 weeks to 133 ml/min at term. Resistivity index values were not correlated with advancing gestational age. The percent of the cardiac output to one of the two middle cerebral arteries remained constant throughout gestation with a range between 3% and 7%. (1) Time velocity integral, peak flow velocity, diameter, and blood flow of the middle cerebral artery increased significantly with gestational age; (2) the percent of the total cardiac output to the middle cerebral artery does not significantly change with gestational age.


cis-Dihydrodiol, arene oxide and phenol metabolites of dictamnine: key intermediates in the biodegradation and biosynthesis of furoquinoline alkaloids.
Biotransformation of the parent furoquinoline alkaloid dictamnine and its 4-chlorofuroquinoline precursor, using the B8/36 bacterial mutant strain of Sphingomonas yanoikuyae, yielded, via biphenyl dioxygenase-catalysed dihydroxylation, the first isolable alkaloid cis-dihydrodiol metabolites; these metabolites were used in the chemoenzymatic synthesis of postulated arene oxide and phenol intermediates, and a range of derived furoquinoline alkaloids.


Use of functional gene expression and respirometry to study wastewater nitrification activity after exposure to low doses of copper.
Autotrophic nitrification in biological nitrogen removal systems has been shown to be sensitive to the presence of heavy metals in wastewater treatment plants. Using transcriptase-quantitative polymerase chain reaction (RT-qPCR) data, we examined the effect of copper on the relative expression of functional genes (i.e., amoA, hao, nirK, and norB) involved in redox nitrogen transformation in batch enrichment cultures obtained from a nitrifying bioreactor operated as a continuous reactor (24-h hydraulic retention time). 16S ribosomal RNA (rRNA) gene next-generation sequencing showed that Nitrosomonas-like populations represented 60-70% of the bacterial community, while other nitrifiers represented <5%. We observed a strong correspondence between the relative expression of amoA and hao and ammonia removal in the bioreactor. There were no considerable changes in the transcript levels of amoA, hao, nirK, and norB for nitrifying samples exposed to copper dosages ranging from 0.01 to 10 mg/L for a period of 12 h. Similar results were obtained when ammonia oxidation activity was measured via specific oxygen uptake rate (sOUR). The lack of nitrification inhibition by copper at doses lower than 10 mg/L may be attributed to the role of copper as cofactor for ammonia monooxygenase or to the sub-inhibitory concentrations of copper used in this study. Overall, these results demonstrate the use of molecular methods combined with conventional respirometry assays to better understand the response of wastewater nitrifying systems to the presence of copper.


Uterine perforation during uterine repositioning on nonpuerperal uterine inversion by delivery of a large fibroid: A case report.
Transvaginal uterine restoration of nonpuerperal uterine inversion is difficult; there are risks of heavy bleeding and uterine perforation. In such cases, total hysterectomy and transfusion are inevitable. A 47-year-old woman with profuse genital bleeding, diagnosed with nonpuerperal uterine inversion caused by a uterine fibroma, underwent emergency surgery. Uterine perforation occurred during transvaginal uterine restoration, revealed by laparoscopy. Bleeding persisted and blood transfusion volume increased; therefore, a total hysterectomy was performed for hemostasis.


[Mechanism of action of alloxan on pancreatic B-cells with special regard to the alloxan-metal-complex theory. II. Actions of alloxan, alloxanic acid, Zn2+ and ethyleneglycol-bis-(beta-aminoethylether)-N,N'tetraacetic acid (EGTA) on the assembly of microtubule proteins (MTP) into microtubules or MPT sheets in vitro].
Analyses of the cell structures in the islets of Langerhans revealed the presence of 2 predominant cations, calcium (beta-granules and saccules, mitochondria, sac membranes, and cell membranes) and zinc (secretory granules, encasing membraneous sacs) in association with organelles which involve directional secretion. Both elements are known to interact with microtubules influencing their structural and functional properties, e.g. movement of secretory granules. Influences of Zn2+ on microtubules are investigated with a view to interactions in vitro with and without diabetogenic substances. Turbidimetry and electron microscopic investigations showed that under the conditions mentioned above, alloxan of a concentration of 2 x 10(-5) mol/l (alloxan/tubulin 1:1) inhibits the formation of microtubules and increases the portion of microtubules stabilized of 4 degrees C. The Zn2(+)-induced formation of MTP sheets is not influenced by alloxan and the metal complex forming agent EGTA, if the molar concentrations of the substance and Zn2+ are equally high. With a molar proportion of 2:1 (EGTA:Zn2+), the formation of sheets does not longer occur and only microtubules are formed, whereas neither sheets nor microtubules were assembled by alloxan with this molar proportion. However, neither the assembly of microtubules nor the formation of Zn2(+)-induced sheets are influenced by alloxanic acid in both molar proportions. It is shown that the diabetogenic alloxan influences the formation of microtubules and that performed microtubules are destroyed. This result of alloxan corresponds to its antimitotic activity analogously to the wellknown effect of colchicine (s. Schmidt et al. 1990).(ABSTRACT TRUNCATED AT 250 WORDS)


Assessing the risk: Scoring systems for outcome prediction in emergency laparotomies.
Emergency laparotomy is the commonest emergency surgical procedure in most hospitals and includes over 400 diverse surgical procedures. Despite the evolution of medicine and surgical practices, the mortality in patients needing emergency laparotomy remains abnormally high. Although surgical risk assessment first started with the ASA Physical Status score in 1941, efforts to find an ideal scoring system that accurately estimates the risk of mortality, continues till today. While many scoring systems have been developed, no single scoring system has been validated across multiple centers and geographical locations. While some scoring systems can predict the risk merely based upon preoperative findings and parameters, some rely on intra-operative assessment and histopathology reports to accurately stratify the risk of mortality. Although most scoring systems can potentially be used to compare risk-adjusted mortality across hospitals and amongst surgeons, only those which are based on preoperative findings can be used for risk prognostication and identify high-risk patients before surgery for an aggressive treatment. The recognition of the fact, that in the absence of outcome data in these patients, it would be impossible to evaluate the impact of quality improvement initiatives on risk-adjusted mortality, hospital groups and surgical societies have got together and started to pool data and analyze it. Appropriate scoring systems for emergency laparotomies would help in risk prognostication, risk-adjusted audit and assess the impact of quality improvement initiative in patient care across hospitals. Large multi-centric studies across varied geographic locations and surgical practices need to assess and validate the ideal and most apt scoring system for emergency laparotomies. While APACHE-II and P-POSSUM continue to be the most commonly used scoring system in emergency laparotomies,studies need to compare them in their ability to predict mortality and explore if either has a higher sensitivity and specificity than the other.


Comparative Analysis of Refractive and Topographic Changes in Early and Advanced Keratoconic Eyes Undergoing Corneal Collagen Crosslinking.
To compare the refractive and topographic changes at 1 year in eyes with early and advanced keratoconus undergoing corneal collagen crosslinking (CXL). A prospective, nonrandomized comparative clinical intervention study. Thirty eyes of patients with keratoconus underwent CXL. They were divided into 2 groups based on their mean central keratometry: group A [mean central K ≤ 53 diopters (D)] and group B (mean central K > 53 D). Uncorrected visual acuity (UCVA), best-corrected visual acuity (BCVA), refraction, topography, pachymetry, and endothelial cell counts were evaluated at baseline and at 1, 3, 6, and 12 months of follow-up. The mean baseline logarithm of the minimum angle of resolution (logMAR) UCVA and logMAR BCVA in group A was 1.007 ± 0.30 and 0.566 ± 0.21, respectively. The values improved to 0.727 ± 0.29 (P = 0.001) and 0.306 ± 0.15 (P = 0.001) at 1-year post CXL. The mean baseline logMAR UCVA and logMAR BCVA in group B were 1.040 ± 0.24 and 0.641 ± 0.25, respectively. It changed to 0.953 ± 0.26 (P = 0.054) and 0.633 ± 0.27 (P = 0.891) at 1 year. The improvement in the UCVA and BCVA was statistically significant in group A as compared with that in group B. The mean baseline flattest, steepest, central, and apical keratometry in group A were 48.7 ± 2.5 D, 54.9 ± 3.3 D, 49.5 ± 1.4 D, and 57.3 ± 2.3 D, respectively. At 12 months, the values changed to 47.8 ± 2.4 D, 54.1 ± 3.0 D, 48.8 ± 1.8 D, and 56.2 ± 2.7 D, the change being statistically significant for mean flat and apical K only (P < 0.05). All the 4 indices did not show any statistically significant difference at 12 months in group B (P > 0.05). Corneal CXL is more effective in improving the refractive and topographical parameters at 1 year when it is performed early in the course of the disease.


On the time dependent diffusion of macromolecules through transient open junctions and their subendothelial spread. 2. Long time model for interaction between leakage sites.
In Part 1 of this study (Weinbaum et al., 1988) a short time model has been proposed to describe the initial time dependent leakage of macromolecules at short distances (5 microns or less) from the exit of a transient open junction which the authors have hypothesized as a characteristic feature of endothelial cells in the process of turnover (Weinbaum et al., 1985). This open junction pathway has also been proposed (Weinbaum et al., 1988) to be the primary ultrastructural correlate of the 20 nm diameter large pore suggested by Renkin et al. (1977) using the predictions of cylindrical pore theory. The short time model in (Weinbaum et al., 1988), however, has major limitations in that it neglects the interaction between leakage sites, macromolecular entry through other pathways, the finite thickness of the vessel wall and the curvature of the cell perimeter. The longer time model developed herein will attempt to describe each of these features and also present an improved model and analytic solution for the steady state flux and uptake. In the previous steady state model developed by Weinbaum et al. (1985) the effect of the resistance of the transient open junctions and the non-isotropic diffusion in the underlying tissue due to the internal elastic lamina (IEL) were both neglected. New solutions are first presented which describe the effect of these important model refinements on the steady state macromolecular permeability of the major arteries. Time dependent solutions are then presented to predict the transient longer time labeling following the introduction of tracer macromolecules of varying size. These solutions and the corresponding short time solutions in Weinbaum et al. (1988) are the first solutions to our knowledge to describe the difficult time-dependent boundary value problem to determine how the channel exit concentration and flux at a leaky junction vary with time. This is accomplished by casting the boundary value problem in the form of an integral equation for the unknown flux at the cleft exit and then solving this problem using a specially designed numerical technique. The theoretical predictions are used to interpret the behavior of the localized leaks to HRP and albumin that have been reported in Stemerman et al. (1986) and our own recent experiments (Lin et al., 1988).


Methods for Ex Vivo AAV Transduction in Rodent and Human Retinal Explants.
Translational research is heavily dependent on animal models, and reliable disease models are essential for the development of novel therapies. Here, we outline the methods for culturing mouse and human retinal explants. In addition, we show efficient adeno-associated virus (AAV) transduction of the mouse retinal explants to aid the study and development of AAV-based therapeutics against ocular diseases.


Epimutation (hypomethylation) affecting the chromosome 14q32.2 imprinted region in a girl with upd(14)mat-like phenotype.
Maternal uniparental disomy for chromosome 14 (upd(14)mat) causes clinically discernible features such as pre- and/or postnatal growth failure, hypotonia, obesity, small hands, and early onset of puberty. The monoallelic expression patterns at the 14q32.2 imprinted region are tightly related to methylation status of the DLK1-MEG3 intergenic differential methylation region (DMR) and the MEG3-DMR that are severely hypermethylated after paternal transmission and grossly hypomethylated after maternal transmission. We examined this imprinted region in a 2 2/12-year-old Japanese patient who was born with a normal birth size (length, +0.2 SD; weight, -0.5 SD) and showed postnatal growth failure (height, -3.1 SD; weight, -3.4 SD), hypotonia, frontal bossing, micrognathia, and small hands. Methylation analysis, genotyping analysis, and deletion analysis were performed with blood samples of the patient and the parents, showing that the DMRs of this patient were grossly hypomethylated in the absence of upd(14)mat and deletion of the DMRs. The results indicate the occurrence of an epimutation (hypomethylation) affecting the normally methylated DMRs of paternal origin, and imply that epimutations should be examined in patients with upd(14)mat-like phenotype.


Types of "H2O" in human enamel and in precipitated apatites.
Types of "H2O" in human enamel and in precipitated apatites are characterized using X-ray diffraction, infrared (IR) absorption spectroscopic and thermogravimetric analyses. Changes in lattice parameters (principally in the a-axis dimensions) and in the character of the IR absorption bands are correlated with weight losses at pyrolysis temperatures of 100 degrees to 400 degrees C and with effect of rehydration and reignition of previously ignited samples. This study demonstrated that the loss of "H2O" below 200 degrees C is reversible and causes no significant change in the lattice parameter of these apatites, whereas loss of "H2O" between 200 degrees and 400 degrees C is irreversible and causes a contraction in the a-axis dimension. It is proposed that two general types of "H2O" are present in these apatites: (a) adsorbed H2O--characterized by reversibility, thermal instability below 200 degrees C, and lack of effect on lattice parameters; and (b) lattice H2O--characterized by irreversibility, thermal instability between 200 and 400 degrees C, and induction of expansion in the a-axis dimensions of human enamel and precipitated apatites. Lattice H2O is assumed to be due to H2O-for-OH and/or HPO4-for-PO4 substitutions in these apatites. Loss of adsorbed H2O caused sharpening of the OH absorption bands in the spectra of these apatites. Loss of lattice H2O caused the appearance of P-O-P absorption bands (due to the presence of P2O74- group) in precipitated apatites containing small amounts of CO32-.


Nonsymmetric [Pt(C^N*N'^C')] Complexes: Aggregation-Induced Emission in the Solid State and in Nanoparticles Tuned by Ligand Structure.
Invited for the cover of this issue are the groups of Sergey P. Tunik and his colleagues from St Petersburg University. The image depicts the strong bathochromic shift of the emission wavelength of phosphorescent platinum(II) complexes upon their aggregation in the presence of water. Read the full text of the article at 10.1002/chem.202202207.


Self healing hydrogels: A new paradigm immunoadjuvant for delivering peptide vaccine.
Immunoadjuvants are added to the vaccines in order to enhance and prolong the antigen specific immune responses when used in consolidation with specific vaccine antigens. This permits the use of antigen in lower quantity and allows immunization protocols practicing the vaccine with smaller doses. Self-healing hydrogels have the ability to heal the damages instinctively and reinstate its framework to ordinariness in absence of external stimuli. Moreover, self-healing hydrogel having various properties such as shear-thinning and reversible sol-gel transformation properties allow it to be readily delivered via injection. Therefore, in the present review, self- healing hydrogel is projected to be used as a carrier for sustained release of peptide and as an analogous to immunoadjuvant. The sustained release property of self-healing hydrogel may be credited to the changes in the structure in response to internal or external stimuli. In addition to the huge potential of stimuli-responsive self-healing hydrogels, they also exhibit good mechanical properties. These properties make self-healing hydrogel as a smart material in delivering the vaccines. Moreover, we have also summarized diverse range of physical and chemical reactions reported for the scale-up of self-healing hydrogels in this review.


A comparative analysis of protein targets of withdrawn cardiovascular drugs in human and mouse.
Mouse is widely used in animal testing of cardiovascular disease. However, a large number of cardiovascular drugs that have been experimentally proved to work well on mouse were withdrawn because they caused adverse side effects in human. In this study, we investigate whether binding patterns of withdrawn cardiovascular drugs are conserved between mouse and human through computational dockings and molecular dynamic simulations. In addition, we also measured the level of conservation of gene expression patterns of the drug targets and their interacting partners by analyzing the microarray data. The results show that target proteins of withdrawn cardiovascular drugs are functionally conserved between human and mouse. However, all the binding patterns of withdrawn drugs we retrieved show striking difference due to sequence divergence in drug-binding pocket, mainly through loss or gain of hydrogen bond donors and distinct drug-binding pockets. The binding affinities of withdrawn drugs to their receptors tend to be reduced from mouse to human. In contrast, the FDA-approved and best-selling drugs are little affected. Our analysis suggests that sequence divergence in drug-binding pocket may be a reasonable explanation for the discrepancy of drug effects between animal models and human.


Neurophysiological monitoring of tongue muscle activation during hypoglossal nerve stimulation.
Upper airway stimulation for obstructive sleep apnea (OSA) via implantable hypoglossal nerve stimulation (HGNS) reduces airway obstruction by selectively stimulating nerve fibers that innervate muscles that produce tongue protrusion, while avoiding fibers that produce tongue retraction. This selective stimulation likely depends upon the location, intensity, and type of electrical stimulation delivered. This study investigates the impact of changing stimulation parameters on tongue muscle activation during HGNS using intraoperative nerve integrity monitoring in conjunction with electromyography (EMG). Prospective case series. Ten patients undergoing unilateral HGNS implantation for OSA in a university hospital setting were studied. Data included EMG responses in tongue muscles that produce protrusion (genioglossus), retraction (styloglossus/hyoglossus), and stiffening (transverse/vertical) in response to intraoperative bipolar probe electrical stimulation of lateral and medial branches of the hypoglossal nerve (HGN) and to implantable pulse generator (IPG) unipolar and bipolar settings after placement of the stimulation cuff. Stimulation of medial division HGN branches resulted in EMG responses in genioglossus muscles, but not in styloglossus/hyoglossus muscles, whereas stimulation of the lateral division HGN branches drove responses in styloglossus/hyoglossus muscles. Variable responses in transverse/vertical muscles were observed with stimulation of lateral and medial division branches. After electrode cuff placement, unipolar and bipolar HGN stimulation configurations of IPG resulted in unique patterns of muscle activation. The relative activation of extrinsic and intrinsic tongue musculature by HGNS is determined by stimulus location, intensity, and type. Intraoperative neurophysiological monitoring of tongue muscle activation enables proper electrode cuff placement and may provide essential data for stimulus optimization. 4 Laryngoscope, 130:1836-1843, 2020.


Advances, shortcomings, and recommendations for wind chill estimation.
This article discusses briefly the advances made and the remaining short-comings in the "new" wind chill charts adopted in the US and Canada in 2001. A number of indicated refinements are proposed, including the use of whole body models in the computations, verification of heat exchange coefficients by human experiments, reconsideration of "calm" wind conditions, reconsideration of frostbite threshold levels, the inclusion of cold-related pain and numbness in the charts, etc. A dynamic numerical model is applied to compare the effects of wind speeds, on the one hand, and air temperatures, on the other, on the steady-state exposed facial and bare finger temperatures. An apparent asymmetry is demonstrated, favoring the effects of wind speeds over those of air temperatures for an identical final facial temperature. This asymmetry is reversed, however, when SI unit changes in these quantities are considered.


A Pilot Study Evaluating the Effectiveness of System-Wide Positive Behavior Support for Institutionalized Orphans in South Korea.
In South Korea, the placement of orphans in institutions is still common, despite evidence of its adverse influence on children's psychological, emotional, physical, and cognitive development. In this preliminary study, we evaluate whether system-wide positive behavior support (SWPBS) is effective for decreasing externalizing problems in institutionalized children. SWPBS was provided for one month to 36 school-aged boys who had lived in an orphanage for an average of 8.72 years (SD=2.52), along with their 10 caregivers. Direct observation of the frequency of target behaviors in the participating children, caregivers' ratings of the severity of children's problematic behaviors, self-reported caregiving stress (i.e., Parenting Stress Scale), and intervention fidelity were dependent variables. After receiving SWPBS, the frequency of problematic behaviors in the participating children showed a mean decrease of 73.6%. The caregivers also reported seeing a decrease in the severity of their children's problematic behaviors after SWPBS compared to before. SWPBS may be a promising intervention to decrease externalizing behaviors in school-aged children who have been living in institutions for a long time and have shown mental health issues.


Immunogenicity and antigenicity of chimeric picornaviruses which express hepatitis A virus (HAV) peptide sequences: evidence for a neutralization domain near the amino terminus of VP1 of HAV.
We evaluated the antigenic characteristics of chimeric picornaviruses created by inserting peptide sequences from hepatitis A virus (HAV) capsid proteins into the B-C loop of VP1 of Sabin strain type 1 poliovirus (PV-1). Fifteen viable chimeras were generated. Each retained the ability to be neutralized by polyclonal PV-1 antisera. Two chimeras (H15 and H2) stimulated production of low levels of HAV neutralizing antibodies in immunized rabbits or mice, although in both cases only a small fraction of immunized animals produced this response. The H15 chimera, which contains residues 13-24 of HAV VP1, elicited HAV neutralizing antibodies in three of nine rabbits and at least one of seven immunized mice. These results indicate that a neutralization domain exists in this region of VP1. However, human sera with high titers of antibodies to HAV failed to neutralize or immunoprecipitate this chimera, suggesting the absence of a significant antibody response to this neutralization domain following natural infection. Sera from rabbits immunized with H15 that did not develop HAV neutralizing antibodies contained antibodies reactive with the HAV peptide segment expressed by the H15 virus, indicating substantial differences in the specificities of antibodies elicited by this peptide segment among individual immunized rabbits. The H15 peptide insert was an effective antigen, as indicated by a high level of sensitivity of the H15 chimera to neutralization by a related anti-peptide antibody which was itself devoid of HAV neutralizing activity. One of 16 rabbits immunized with the H2 chimera (residues 101-108 of HAV VP1) developed HAV neutralizing antibodies, confirming both the presence and the highly conformational nature of a neutralization antigenic site involving these residues of HAV.


Actions of dopamine on prolactin secretion and cyclic AMP metabolism in ovine pituitary cells.
Prolactin secretion from cultured sheep pituitary cells was inhibited by low concentrations of dopamine (0.1 nM-0.1 microM) with a half-maximal effect at 3 nM. At a maximally effective dose (0.1 microM) dopamine significantly inhibited prolactin secretion within 5 min. with an 80% inhibition of basal secretion over 2 h. Basal prolactin secretion was stimulated by the addition of methylisobutylxanthine (MIX) (0.3-1.0 mM) and 8-bromo-cyclic AMP (2 mM), but cholera toxin (3 micrograms/ml) and prostaglandin E2 (0.1-1.0 microM), which also raised cellular cyclic AMP levels, had no effect on prolactin release. The inhibition of prolactin release by dopamine (0.1 microM) was not affected by any of these compounds. Dopamine inhibited MIX-induced cyclic AMP accumulation over a similar concentration range to the inhibition of secretion, but had no effect on the changes in cyclic AMP concentration produced by cholera toxin and prostaglandin E2. Overall the results with sheep pituitary cells suggest that lowered cyclic AMP levels do not mediate the inhibitory effects of dopamine on basal prolactin secretion, but that changes in cellular cyclic AMP levels may alter the secretion of this hormone, and dopamine may affect pituitary cell cyclic AMP concentrations in some circumstances.


Climatic variations and pollution on benign paroxysmal positional vertigo in Kars, Türkiye.
Benign paroxysmal positional vertigo (BPPV) is the most common diagnosis for peripheral vertigo. Although pathophysiological mechanisms remain unclear, BPPV is mostly idiopathic and factors related to BPPV are still being investigated. Knowing these factors can contribute to the prevention and management of BPPV. In this study, we investigated the correlations between climatic variations, pollution, and BPPV retrospectively. 262 patients diagnosed with BPPV between 2019 and 2021 in Kars, Türkiye, were included in our study. Meteorological parameters were obtained from Turkish State Meteorological Service. Horizontal BPPV increased significantly with the humidity (p < 0.05). In addition, carbon monoxide levels significantly increased the potantial of BPPV (p < 0.05). Surprisingly, BPPV increased in the summertime and showed a significant relationship with humidity. We believe this change is related with the city-specific features as it is the coldest place in the country, emigrant province and crowded in the summer times.


Cause-specific mortality of very preterm infants and antenatal events.
To assess the relationship between antenatal factors and cause-specific risk of death in a large area-based cohort of very preterm infants. The ACTION (Accesso alle Cure e Terapie Intensive Ostetriche e Neonatali) study recruited during an 18-month period all infants 22-31 weeks' gestational age admitted to neonatal care in 6 Italian regions (n=3040). We analyzed the data of 2974 babies without lethal or acutely life-threatening malformations. Cause-specific risks of death adjusted for competing causes were calculated, and region-stratified multiple Cox regression analyses were used to study the association between cause-specific mortality and infants' characteristics, pregnancy complications, antenatal steroids, and place of birth. Deaths attributable to respiratory problems and intraventricular hemorrhage prevailed in the first 2 weeks of life, and those attributable to infections and gastrointestinal diseases afterwards. Antepartum hemorrhage was associated with respiratory deaths (hazard ratio [HR] 1.6, 95% CI 1.1-2.4), and maternal infection with deaths attributable to asphyxia (HR 32.5, 95% CI 4.1-259.4) and to respiratory problems (HR 2.8, 95% CI 1.6-5.2). Preterm premature rupture of membranes increased the likelihood of deaths due to neonatal infection (HR 1.8, 95% CI 1.0-3.1), and preterm labor/contractions of those due to respiratory (HR 1.5, 95% CI 1.1-2.0) and gastrointestinal diseases (HR 5.8, 95% CI 2.1-16.3). In addition, a birth weight z-score<-1 was associated with increasing hazards of death resulting from asphyxia, late infections, respiratory, and gastrointestinal diseases. Different complications of pregnancy lead to different cause-specific mortality patterns in very preterm infants.


Effects of cinnamic acid on expression of tissue factor induced by TNFalpha in endothelial cells and its mechanisms.
To observe the effects of cinnamic acid (CINN) on the expression of tissue factor (TF) induced by tumor necrosis factor alpha (TNFalpha) in human umbilical vein endothelium-derived cell line (ECV304) and the related mechanisms. Cellular TF activity was determined with 1-stage clotting assay in the presence or absence of anti-TF antibody or DEGR-Vlla. TF mRNA was examined by semi-quantitative reverse transcription polymerase chain reaction (RT-PCR). I-kappaB was measured by Western blot analysis. Immunohistochemical analysis was performed to evaluate the activation of NF-kappaB. CINN (500 microg/mL) significantly decreased the TF activity in ECV304 induced by TNFalpha (1000 U/mL) (p < 0.01) in a concentration-dependent fashion (r = -0.953, p < 0.05). CINN also inhibited the expression of TF mRNA induced by TNFalpha. Immunohistochemical analysis demonstrated NF-kappaB translocation from the cytoplasm to the nucleus, and Western blot analysis showed I-KB decrement in cytoplasm after treatment of endothelial cells with TNFalpha. CINN diminished these changes induced by TNFalpha. CINN is able to attenuate TNFa-induced TF expression of vascular endothelial cells by inhibiting NF-kappaB activation.


IGF-I levels and visceral fat accumulation in colonic neoplasia.
IGF-I, visceral obesity, IGF binding protein-3 and insulin are reported to be potential risk factors for colorectal carcinogenesis. Many studies report a relation between obesity, insulin resistance and the risk of colon cancer. This study investigates the association between IGF-I levels, insulin resistance and visceral fat accumulation in patients with colon cancer and adenoma. In this cross sectional study, 48 sequential patients were diagnosed with either colorectal adenoma or carcinoma were enrolled. The control subjects were 30 sequential subjects. Serum IGF-I, HOMA insulin resistance index and visceral fat were measured in patients with colorectal adenoma and carcinoma. Serum IGF-I levels were significantly higher in patients with colorectal adenoma and carcinoma compared with controls. Visceral fat accumulation was lower in colorectal carcinoma group compared with colorectal adenoma group, but no statistically significant difference was observed among them and controls. No statistically significant difference was observed in HOMA insulin resistance index, fasting insulin and fasting glucose concentrations among the three groups. No correlation was found between insulin resistance and serum IGF-I levels and visceral fat accumulation. Logistic regression analysis showed that plasma IGF-I concentration was significantly associated with colorectal adenoma and carcinoma. Body mass index and waist circumference were associated with colorectal, carcinoma but were not associated with adenoma. In our study we found that, IGF-I levels are associated with colorectal adenomas and carcinomas, independent of insulin resistance and visceral fat accumulation; supporting the hypothesis that an increase in IGF-I levels may be a factor involved in the development of colon cancer.


Dynamic Ion Speciation during the Hydrolysis of Aryltrifluoroborates*.
Organotrifluoroborates serve as coupling partners during transmetalation in the Suzuki-Miyaura reaction but require hydrolysis prior to the coupling reaction. Their anionic nature allows study of their hydrolysis by electrospray ionization mass spectrometry (ESI-MS) through real-time monitoring, complemented by pH analysis. The induction period varied according to the borates employed, and a dynamic series of equilibria for numerous ions was observed during hydrolysis. We found that the induction periods and reaction rates were sensitive to the R group of the borates, the shape of the reaction vessel, and stir rate.


Secondary intracerebral blastomycosis with giant yeast forms.
Secondary central nervous system (CNS) blastomycosis is an unusual manifestation of blastomycosis. We report a case of recurrent intracerebral blastomycosis that presented histopathologically with giant yeast-like cells and multinucleation that mimicked Coccidioides immitis. The yeast forms of Blastomyces dermatitidis usually range in size from 8 to 20 microm in diameter. Large or giant yeast forms (20-40 microm) are rare. The four cases previously reported in the literature involving giant yeast cell forms of B. dermatitidis are reviewed here. Intracerebral blastomycosis should be suspected in patients with signs and symptoms of CNS lesions and histories of primary blastomycosis, or treatment with corticosteroids, or comprised immune systems. The diagnosis should be confirmed by culture which presents typical biphasic microbiologic features.


Intracellular trafficking of superparamagnetic iron oxide nanoparticles conjugated with TAT peptide: 3-dimensional electron tomography analysis.
Internalisation of nanoparticles conjugated with cell penetrating peptides is a promising approach to various drug delivery applications. Cell penetrating peptides such as transactivating transcriptional activator (TAT) peptides derived from HIV-1 proteins are effective intracellular delivery vectors for a wide range of nanoparticles and pharmaceutical agents thanks to their amicable ability to enter cells and minimum cytotoxicity. Although different mechanisms of intracellular uptake and localisation have been proposed for TAT conjugated nanoparticles, it is necessary to visualise the particles on a 3-D plane in order to investigate the actual intracellular uptake and localisation. Here, we study the intracellular localisation and trafficking of TAT peptide conjugated superparamagnetic ion oxide nanoparticles (TAT-SPIONs) using 3-D electron tomography. 3-D tomograms clearly show the location of TAT-SPIONs in a cell and their slow release from the endocytic vesicles into the cytoplasm. The present methodology may well be utilised for further investigations of the behaviours of nanoparticles in cells and eventually for the development of nano drug delivery systems.


Neurodevelopmental outcomes of tracheoesophageal fistulas.
The purpose of this study was to perform a retrospective review of tracheoesophageal fistula (TEF) patients who followed up in a state-sponsored program to assess neurodevelopmental outcomes. Records were reviewed retrospectively of children who underwent TEF repair between August 2001 and June 2014. Children discharged from the neonatal intensive care unit were referred to the state-sponsored Developmental Tracking Infant Progress Statewide (TIPS) program. We reviewed TIPS assessments performed before age 24months and noted referral for early school intervention services. Poor outcomes were defined as scores of "failure" on the screening assessment or referral for enrollment in early intervention services by 24months. Children with TEF were compared with case-matched nonsyndromic children of similar gestational age and birth weight. Seventy-eight children underwent TEF repair. Thirty-eight followed up with TIPS. Survival was 93.6%. Predictors of hospital survival were Waterston classification (p=0.001), birth weight (p=0.027), and ventilator days (p=0.013). LOS was the only significant predictor of referral for early intervention services (p=0.0092) in multivariate analysis. There was a borderline significant difference in referral rate between children with TEF and controls. 52.6% of TEF patients were referred, while 34.2% of controls were referred (p=0.071). More than half of TEF patients experience neurodevelopmental delays requiring referral for early intervention (53%).


Inhibition of human glutathione S-transferases by dopamine, alpha-methyldopa and their 5-S-glutathionyl conjugates.
The reversible and irreversible inhibition of human glutathione S-transferases (GST) by dopamine, alpha-methyldopa and their 5-S-glutathionyl conjugates (termed 5-GSDA and 5-GSMDOPA, respectively) was studied using purified isoenzymes. The reversible inhibition, using CDNB as substrate and expressed as I50, ranged from 0.18-0.24 (GST M1a-1a), 0.19-0.24 (GST M1b-1b) to 0.5-0.54 mM (GST A1-1) for 5-GSDA and 5-GSMDOPA, respectively. About 20% inhibition was observed for GST A2-2 and P1-1, using 0.5 mM of both 5-GSDA and 5-GSMDOPA. No significant reversible inhibition was observed with dopamine and alpha-methyldopa. Tyrosinase was used to generate ortho-quinones from dopamine and alpha-methyldopa which may bind covalently to GST and thereupon irreversibly inhibit GST. In this respect, GST P1-1 was by far the most sensitive enzyme. The inhibition (expressed as a % of control) after incubating 0.5 microM GST in the presence of 100 units/ml tyrosinase with 5 microM of the catecholamines for 10 min at 25 degrees, was 99% and 67% for dopamine and alpha-methyldopa, respectively. Moderate irreversible inhibition of GST A1-1 by both dopamine and alpha-methyldopa (33% and 25%, respectively), and of GST M1b-1b by dopamine (45%) was also observed. GST P1-1 is also the only isoenzyme susceptible to irreversible inhibition by 5-GSDA (33% inhibition), while no significant inhibition was observed with 5-GSMDOPA. A minor part of the inhibition by dopamine (23%), and the complete inhibition by 5-GSDA was restored by reduction with dithiotreitol. This suggests that GST P1-1 is inhibited by disulfide formation in the case of 5-GSDA, while this oxidative pathway also substantially contributes to the inactivation by dopamine. This was supported by the HPLC-profile of the GST P1-1 subunit which was strongly affected by dopamine, while for 5-GSDA after reduction with dithiotreitol the original elution profile of the subunit returned.


In vitro compressive properties of skeletal muscles and inverse finite element analysis: Comparison of human versus animals.
Virtual finite element human body models have been widely used in biomedical engineering, traffic safety injury analysis, etc. Soft tissue modeling like skeletal muscle accounts for a large portion of a human body model establishment, and its modeling method is not enough explored. The present study aims to investigate the compressive properties of skeletal muscles due to different species, loading rates and fiber orientations, in order to obtain available parameters of specific material laws as references for building or improving the human body model concerning both modeling accuracy and computational cost. A series of compressive experiments of skeletal muscles were implemented for human gastrocnemius muscle, bovine and porcine hind leg muscle. To avoid long-time preservation effects, all experimental tests were carried out in 24 h after that the samples were harvested. Considering computational cost and generally used in the previous human body models, one-order hyperelastic Ogden model and three-term simplified viscoelastic quasi-linear viscoelastic (QLV) were selected for numerical analysis. Inverse finite element analysis was employed to obtain corresponding material parameters. With good fitting records, the simulation results presented available material parameters for human body model establishment, and also indicated significant differences of muscle compressive properties due to species, loading rates and fiber orientations. When considering one-order Ogden law, it is worthy of noting that the inversed material parameters of the porcine muscles are similar to those of the human gastrocnemius regardless of fiber orientations. In conclusion, the obtained material parameters in the present study can be references for global human body and body segment modeling.


Validation of intra-operative parathyroid hormone and its decline as early predictors of hypoparathyroidism after total thyroidectomy: A prospective cohort study.
Total thyroidectomy is a preferred surgical technique for benign as well as malignant thyroid pathologies, but many a times can cause hypoparathyroidism. The aim of this study is to evaluate the intra-operative parathyroid hormone (ioPTH) level and its decline as predictors for post-operative hypoparathyroidism after total thyroidectomy. In this single-centre prospective cohort study, 90 patients who underwent total thyroidectomy for benign as well as malignant pathologies of thyroid gland were studied. Intra-operative parathyroid levels and at different time intervals parathyroid hormone and serum calcium levels were measured to predict hypoparathyroidism. The data was analysed using independent sample t test and p value < .05 was considered to be significant. There were 14 male and 76 female patients with a mean age of 41 years. Most common thyroid pathology for which total thyroidectomy was done was colloid goitre (62). Twenty four patients (26.66%) developed hypoparathyroidism. Intra-operative PTH was found to be most accurate predictor for diagnosing post-operative hypoparathyroidism (cut off was (11.3 pg/ml, calculated using ROC curves) and has maximum sum of sensitivity (91.7%) and specificity (97%). On taking cut off values of intra-operative PTH and PTH decline together, they were found to be most accurate predictor for permanent hypoparathyroidism. Early and accurate predictor of hypoparathyroidism is very important and always sought. Very early prediction during intra-operative periods can be used for auto transplantation of parathyroid gland. Intra-operative parathyroid hormone and its decline are accurate, reliable, and early predictor of hypoparathyroidism after total thyroidectomy.


Rab32/38 and the xenophagic restriction of intracellular bacteria replication.
Rab GTPases' subversion by intracellular pathogens during infection has been extensively documented. Recent findings have implicated a key intracellular bacterial restriction/containment function for Rab32/38 in Salmonella species in macrophages and Listeria monocytogenes in dendritic cells. Rab32/38 aids the phagolysosome maturation, and mediates a parallel xenophagy mechanism by engaging prohibitins.


Serum CEA and CA 15-3 as prognostic factors in primary breast cancer.
In the present study, we investigated the association of the serum levels of the tumour markers carcinoembryonic antigen and cancer antigen 15-3 with disease free survival and death from disease in 1046 women with breast cancer without metastases at the time of primary diagnosis in relation to age and the established prognostic factors tumour size, lymph node status, histological grading and hormone receptor status. We found that elevated pre-operative serum marker values were correlated with early relapse (cancer antigen 15-3; P=0.0003) and death from disease (carcinoembryonic antigen, cancer antigen 15-3; P=0.0001 both) in univariate analyses. By comparing pre- and post-operative values we found a decline in values post-surgery. In those patients where marker levels of carcinoembryonic antigen decreased more than 33%, a significantly higher risk for relapse and death from disease (both P=0.0001) in univariate analyses was observed. In multivariate analysis this decrease of carcinoembryonic antigen proved to be an independent prognostic factor. The results for cancer antigen 15-3 were comparable to carcinoembryonic antigen in univariate analyses but showed no significance in multivariate analysis. In this study the post-operative decrease of the serum tumour marker carcinoembryonic antigen was a strong independent prognostic factor for disease free survival and death from disease in breast cancer patients.


Assistance to patients eligible for palliative care: the view of professionals from an Intensive Care Unit.
to understand the perception of the multiprofessional team about the quality of health care provided to patients in palliative care in the Intensive Care Unit. qualitative study, anchored to Donabedian's theoretical framework, through semi-structured interviews with 35 professionals working in the Intensive Care Unit. For data analysis, the Content Analysis technique was used. three categories were pre-established: structure, process, and outcome, from which five subcategories emerged: Deficit in terms of numbers of workers and professional qualification; Ambience and palliative care; (In)existence of assistance based on the principles of palliative care; Failures in communication and in the interdisciplinary approach and Repercussions of (lack of) assistance. the study allowed understanding the institutional weaknesses for the operationalization of care provided to patients eligible for palliative care in the Intensive Care Unit setting. Thus, for this philosophy of care to be propagated, the co-participation of managers, professionals, patients, and family members is required, since these gaps cannot be filled without collective involvement.


Mental health consultation in a home care agency.
A mental health nurse, educationally and clinically prepared as a specialist, can be effectively utilized as a consultant to aid nurse generalists in assessment and intervention of patients in a home health care agency. An individual staff nurse consulting with the specialist or a group of nurses provides the setting for consultant led case discussions. Consultation is a highly efficient use of specialist's knowledge and skills in health care delivery, and also provides learning opportunities for staff.


Selection bias in the study of spouse similarity for psychiatric morbidity in clinical samples.
The existing literature on spouse similarity for health variables can be divided into two fields of application, high blood pressure and other coronary risk factors and psychiatric morbidity. In the former field, almost all studies have been conducted on general-population samples, whereas in the psychiatric field, most of the investigations studied clinical samples, i.e., where one or both members of the couple were under psychiatric treatment. In this report, we demonstrate that studies of spouse similarity for psychiatric morbidity are subject to selection bias whenever they are conducted on clinical samples. This selection bias has a double origin. First, some bias arises from the fact that the probability of a couple being drawn for a clinical sample is dependent on whether one or both spouses are afflicted with the illness in question. A second source of bias lies in the likelihood that each spouse's help-seeking behavior is not independent of the other's. It would appear then that, owing to this selection bias, it is preferable to restrict the study of spouse similarity for psychiatric morbidity to general-population samples.


Clinical impact of Sim & Size® simulation software in the treatment of patients with cerebral aneurysms with flow-diverter Pipeline stents.
This study evaluated the clinical impact of the Sim&Size® simulation software on the endovascular treatment with flow-diverter stents of patients with unruptured saccular intracranial aneurysms. This monocentric retrospective study evaluated a cohort of patients treated with flow-divert stents between June 1, 2014, and December 31, 2019, for cerebral aneurysms. Patients belonged to two groups, patients treated with and without the Sim&Size® simulation software. Univariate, bivariate, and multivariate analyses were used to evaluate the clinical impact of simulation software. Out of the 73 interventions involving 68 patients analyzed by the study, 76.7% were simulated using the Sim&Size® simulation software, and 23.3% were not. Patients treated with the simulation software had shorter stent lengths (16.00 mm vs. 20.00 mm p-value = 0.001) and surgical time (100.00 min vs. 118.00 min p-value = 0.496). Also, fewer of them required more than one stent (3.6% vs. 17.6% p-value = 0.079). Three patients belonging to the non-stimulated group presented hemorrhagic complications. Using the Sim&Size® simulation software for the endovascular treatment of intracranial aneurysms with pipeline flow-diverter stents reduces the stent length.


Enhanced bioavailability of cefoxitin using palmitoylcarnitine. II. Use of directly compressed tablet formulations in the rat and dog.
The performance of tablets containing the absorption enhancer palmitoylcarnitine chloride (PCC) and the antibiotic cefoxitin (CEF) was determined by direct placement of tablets in the rat stomach, small intestine, and colon. While the bioavailability (F) of tablets containing 12 mg CEF without PCC ranged from 0.6 to 3.9%, the addition of 24 mg PCC resulted in an enhanced CEF bioavailability in the rat colon (mean +/- SD: F = 57 +/- 19%) and rat jejunum (F = 71 +/- 16%) but not in the rat stomach. Following oral administration to dogs, tablets of 200 mg CEF without or with 600 mg PCC resulted in the same low bioavailabilities (7.0 +/- 10.3 and 7.0 +/- 3.6%, respectively). However, when these tablets were enteric coated, PCC improved CEF bioavailability from 2.44 +/- 1.84 to 29.0 +/- 13.4%. Therefore, the use of enteric-coated direct compressed tablets containing PCC and direct compression excipients improved the peroral bioavailability of a poorly absorbed compound.


Antimicrobial resistance (AMR) and plant-derived antimicrobials (PDAms) as an alternative drug line to control infections.
Infectious diseases caused by antimicrobial-resistant microbes (ARMs) and the treatment are the serious problems in the field of medical science today world over. The development of alternative drug line to treat such infectious diseases is urgently required. Researches on ARMs revealed the presence of membrane proteins responsible for effusing the antibiotics from the bacterial cells. Such proteins have successfully been treated by plant-derived antimicrobials (PDAms) synergistically along with the commercially available antibiotics. Such synergistic action usually inhibits the efflux pump. The enhanced activity of plant-derived antimicrobials is being researched and is considered as the future treatment strategy to cure the incurable infections. The present paper reviews the advancement made in the researches on antimicrobial resistance along with the discovery and the development of more active PDAms.


Management of Testicular Torsion and a Contralateral Testicular Mass Presenting Synchronously.
Testicular masses found in prepubertal males are often benign in nature. This has led to an increase in the use of testis-sparing surgery. Testicular torsion is considered a urologic emergency that requires immediate surgical intervention. Based off literature review, it is rare for these unique entities to present synchronously in a single patient. This report demonstrates that in the pediatric population it is possible to safely treat a suspected benign testicular mass with testis sparing mass enucleation if it presents synchronously with testicular torsion in the contralateral testis.


A graph-theoretic approach to modeling metabolic pathways.
The metabolic pathways of medazepam, oxazepam, and diazepam were modeled using graph-theoretic transforms which are incorporable into computer-assisted metabolic analysis programs. The information, represented in the form of a graph-theoretic transform kit, which was obtained from these pathways was then used to predict the metabolites of other benzodiazepine compounds. The transform kits gave statistically significant predictions with respect to a statistical method for evaluating the performance of the transform kits.


Long-term water temperature reconstructions from mountain lakes with different catchment and morphometric features.
Long-term water temperature records are necessary for better understanding climate change impacts on freshwaters. We reconstruct summer water temperatures from three climatically sensitive mountain lakes in Austria using paleolimnological methods aiming to examine long-term thermal dynamics and lakes' responses to regional climate variability since the Little Ice Age. Our results indicate divergent trends for the lakes. In two of the lakes, which are located at the sunny southern slope of mountains, water temperature has increased several degrees concurrent with the observed air temperature increase. In contrast, no change is observed in the reconstructed water temperatures of a shaded lake, located at the northern slope, where also the ecological and thermal changes are most subtle. The results indicate the importance of cold water inputs, such as snowmelt and groundwater, on lakes' thermal conditions and suggest that watershed characteristics and lake stratification play a major role in defining the lake-specific thermal regime.


Retrograde axonal transport of antibodies to synaptic membrane components.
It is well known that several exogenous substances, including, for example, lectins, nerve growth factor and several toxins, are retrogradely transported in axons after selectively binding to molecules on the surface of the synaptic membrane. In the present study, we sought to determine if antibodies to components of the synaptic membrane are also retrogradely transported. Retrograde axonal transport of antibodies to the Con A-positive fraction of synaptic membranes was studied in the rat hypoglossal and facial nerves. After injection of antibodies into the tongue and facial muscles, labeled cells were present in the hypoglossal nucleus and facial nucleus, respectively. Injections of normal serum produced no labeling in either system.


Diagnosis and treatment in a case of juvenile subacute necrotizing encephalopathy Leigh without cytochrome c oxidase deficiency.
Subacute necrotizing encephalopathy (Leigh syndrome) is characterized by lactacidosis, seizures, ataxia, multiple cerebral hypervascularized lesions and mitochondrial oxidation defects. This is a report on a 21-year-old patient with proven Leigh syndrome, mild central and provokable peripheral lactacidosis, an extra-erythrocyte complex II defect, functionally reduced myokinase adenylate deaminase activity, but no ultrastructural mitochondrial changes. Determination of lactate, pyruvate and ammonia under ischemic conditions plus a pyruvate loading test were particularly useful. Oral flunarizine (Sibelium 30 mg/d) proved to be therapeutically effective.


Synthesis, characterization and antimicrobial investigation of some moxifloxacin metal complexes.
The new complexes of moxifloxacin (MOX), with Ti(IV), Y(III), Pd(II) and Ce(IV) have been synthesized. These complexes were then characterized by melting point, magnetic studies and spectroscopic techniques involving infrared spectra (IR), UV-Vis, (1)H NMR. C, H, N and halogen elemental analysis and thermal behavior of complexes also investigated. The results suggested that the molar ratio for all complexes is M: MOX=1:2 where moxifloxacin acts as a bidentate via one of the oxygen atoms of the carboxylate group and through the ring carbonyl group and the complexes have the following formula [Ti(MOX)(2)](SO(4))(2)·7H(2)O, [Y(MOX)(2)Cl(2)]Cl·12H(2)O, [Pd(MOX)(2)(H(2)O)(2)]Cl(2)·6H(2)O and [Ce(MOX)(2)](SO(4))(2)·2H(2)O. The activation energies, E*, enthalpies, ΔH*, entropies, ΔS* and Gibbs free energies, ΔG*, of the thermal decomposition reactions have been derived from thermogravimetric (TGA) and differential thermogravimetric (DrTG) curves, using Coats-Redfern (CR) and Horowitz-Metzger (HM) methods. The antimicrobial activity of these complexes has been evaluated against three Gram-positive and three Gram-negative bacteria and compared with the reference drug moxifloxacin. The antibacterial activity of Ti(IV) complex is significant for E. coli K32 and highly significant for S. aureus K1, B. subtilis K22, Br. otitidis K76, P. aeruginosa SW1 and K. oxytoca K42 compared with free moxifloxacin.


Incidence, risk factors and management of delayed wound dehiscence after craniotomy for tumor resection.
Dehiscence after a wound has healed is a known complication of craniotomy for tumor resection. We conducted a retrospective analysis of 64 patients who underwent craniotomy for tumor resection followed by radiation or radiosurgery between 2006 and 2010. Five patients (7.8%) were identified who showed wound dehiscence from two to eight months after the craniotomy wound had healed. Four patients had previously undergone additional craniotomies, additional radiosurgery or had been treated with the anti-angiogenic factor, bevacizumab. These treatments may be risk factors for developing delayed dehiscence and, in combination, may potentiate local wound healing problems. Potential mechanisms and management strategies are discussed.


Detection and molecular characterization of rabies virus isolates from humans in Cameroon.
Despite the enzootic cycle of rabies in dog populations, laboratory confirmation of human rabies has been hardly reported in Cameroon. This study aimed to determine the rate of molecular detection and phylogenetic relatedness of Rabies Virus (RABV) isolates from suspected human rabies cases in Cameroon. From 2014 to 2018, 21 suspected human rabies cases were tested for RABV genomic RNA. Full-length sequence of the nucleoprotein (N) coding gene of RABV isolates detected were generated and subjected to phylogenetic analyses. As results, skin biopsies and/or saliva samples from 10 of the 21 suspected human rabies cases were positive for genomic RABV RNA. Four new N gene sequences were generated from confirmed cases. The studied RABV isolates fell into the Cosmopolitan clades, sub-clades Africa-1a and 1b. This study showed a low rate of molecular detection of RABV in suspected human rabies cases; thus, underscoring the interest of systematic laboratory confirmation.


A robust tag-free aptasensor for fluorescent detection of kanamycin assisted by signal intensification potency of rolling circle amplification.
Rolling circle amplification (RCA) process as an excellent DNA amplifier strategy possesses the merits of high performance and easy operation. In this research, a sensitive RCA-based fluorescent aptasensor was fabricated for the detection of kanamycin residues in food. The aptasensing approach consisted of two main steps; immobilization of biotinylated kanamycin aptamer on streptavidin magnetic beads (SMB) and separation of free complementary strands (CS) from the SMB-aptamer/kanamycin at the first step. For the second step, RCA procedure was applied as signal magnifier and SYBR Green was added as fluorescent indicator dye. The linear relation between the aptasensor response and kanamycin concentration was obtained from 5 nM to 100 nM with the detection limit of 1.93 nM (S/N = 3). The aptasensor displayed satisfactory selectivity among other antibiotics. The developed aptasensor is reliable for monitoring kanamycin in milk as a common foodstuff.


Serum and tissue transforming [corrected] growth factor β1 in children with biliary atresia.
Biliary atresia (BA) is an infantile disorder characterized by the obstruction of a portion or the entirety of the extrahepatic bile ducts, leading to hepatic fibrosis and loss of liver function. The gold standard for diagnosing and grading fibrosis is liver biopsy, but there are many groups searching for noninvasive biomarkers that could replace and/or complement this procedure. In this study, we evaluated serum and tissue transforming growth factor β1 (TGFβ1) and aspartate aminotransferase [AST]-to-platelet ratio index (APRI) in patients with BA at the time of diagnosis and at liver transplantation and correlated these data with tissue collagen density, to verify if they could act as biomarkers for BA. At the time of diagnosis, TGFβ1 levels were highly variable in BA patients. However, serum values at transplantation were significantly decreased (13.75 ± 3.68 ng/mL) as compared to controls (34.36 ± 9.35 ng/mL) (P = .01). No correlation was found between serum TGF1β1 and collagen density in both groups analyzed. Serum TGFβ1 showed no correlation with APRI at diagnosis. At the time of liver transplantation, all patients had low serum TGFβ1 and variable APRI, although all higher than 2.0. However, when platelet count was used, an inverse correlation with serum TGFβ1 was observed at the time of diagnostics (r(2) = 0.749; P = .03). Our findings suggest that at the time of diagnosis the fibrogenic process is active, with higher levels of TGFβ1, whereas later on, there is scar tissue, with reduced TGFβ1 expression. Although our results should be confirmed in larger sets of patients with BA, the lack of TGFβ1 at the time of liver transplantation may have important consequences for the patient because it is a pleiotropic molecule, responsible for many functions in the body, mainly those related to immune response and cell growth.


Developing an Automated Assessment of In-session Patient Activation for Psychological Therapy: Codevelopment Approach.
Patient activation is defined as a patient's confidence and perceived ability to manage their own health. Patient activation has been a consistent predictor of long-term health and care costs, particularly for people with multiple long-term health conditions. However, there is currently no means of measuring patient activation from what is said in health care consultations. This may be particularly important for psychological therapy because most current methods for evaluating therapy content cannot be used routinely due to time and cost restraints. Natural language processing (NLP) has been used increasingly to classify and evaluate the contents of psychological therapy. This aims to make the routine, systematic evaluation of psychological therapy contents more accessible in terms of time and cost restraints. However, comparatively little attention has been paid to algorithmic trust and interpretability, with few studies in the field involving end users or stakeholders in algorithm development. This study applied a responsible design to use NLP in the development of an artificial intelligence model to automate the ratings assigned by a psychological therapy process measure: the consultation interactions coding scheme (CICS). The CICS assesses the level of patient activation observable from turn-by-turn psychological therapy interactions. With consent, 128 sessions of remotely delivered cognitive behavioral therapy from 53 participants experiencing multiple physical and mental health problems were anonymously transcribed and rated by trained human CICS coders. Using participatory methodology, a multidisciplinary team proposed candidate language features that they thought would discriminate between high and low patient activation. The team included service-user researchers, psychological therapists, applied linguists, digital research experts, artificial intelligence ethics researchers, and NLP researchers. Identified language features were extracted from the transcripts alongside demographic features, and machine learning was applied using k-nearest neighbors and bagged trees algorithms to assess whether in-session patient activation and interaction types could be accurately classified. The k-nearest neighbors classifier obtained 73% accuracy (82% precision and 80% recall) in a test data set. The bagged trees classifier obtained 81% accuracy for test data (87% precision and 75% recall) in differentiating between interactions rated high in patient activation and those rated low or neutral. Coproduced language features identified through a multidisciplinary collaboration can be used to discriminate among psychological therapy session contents based on patient activation among patients experiencing multiple long-term physical and mental health conditions.


Morphine tolerance in male and female rats.
Several studies indicate greater sensitivity to morphine (MOR) analgesia in male compared to female rats under the acute dosing condition. The present study investigated whether the same sex difference in sensitivity persists in MOR-tolerant rats. MOR was administered chronically (7 mg/kg twice daily) until tolerance developed in each rat. Tolerant rats were treated randomly with higher graded doses of MOR (10-25 mg/kg). Analgesia (tail-flick test) and spontaneous motor activity (total locomotion) were measured. The present data confirmed previous studies showing a greater sensitivity to acute MOR in male than in female rats. However, the sex differences seen in MOR sensitivity were abolished in tolerant rats. The rate of acquisition of tolerance was similar in male and female rats. The analgesic response was not affected by motor depression.


Multi-walled carbon nanotubes as a solid-phase extraction adsorbent for the determination of chlorophenols in environmental water samples.
Multi-walled carbon nanotubes (MWCNs) are used as adsorbent for solid-phase extraction (SPE) of several chlorophenols (CPs). CPs were adsorbed on MWCNs cartridge, then desorbed with pH 10.0 methanol, finally determined by HPLC. Under the optimized conditions, detection limits of 0.08-0.8 ng mL(-1) were obtained. The method had been applied to analyze the five CPs in tap water and river water.


Value-oriented citizenship index: New extensions of Kelman and Hamilton's theory to prevent autocracy.
In Crimes of obedience, Kelman and Hamilton argue that societies can be protected by the degeneration of authority only when citizenship is based on a strong values orientation. This reference to values may be the weakest point in their theory because they do not explicitly define these values. Nevertheless, their empirical findings suggest that the authors are referring to specific democratic principles and universal values (e.g., equality, fairness, harmlessness). In this article, a composite index known as the value-oriented citizenship (VOC) index is introduced and empirically analysed. The results confirm that the VOC index discriminates between people who relate to authority based on values rather than based on their role or on rules in general. The article discusses the utility of the VOC index to develop Kelman and Hamilton's framework further empirically as well as its implications for the analysis of the relationship between individuals and authority.


Monte Carlo simulations for the space radiation superconducting shield project (SR2S).
Astronauts on deep-space long-duration missions will be exposed for long time to galactic cosmic rays (GCR) and Solar Particle Events (SPE). The exposure to space radiation could lead to both acute and late effects in the crew members and well defined countermeasures do not exist nowadays. The simplest solution given by optimized passive shielding is not able to reduce the dose deposited by GCRs below the actual dose limits, therefore other solutions, such as active shielding employing superconducting magnetic fields, are under study. In the framework of the EU FP7 SR2S Project - Space Radiation Superconducting Shield--a toroidal magnetic system based on MgB2 superconductors has been analyzed through detailed Monte Carlo simulations using Geant4 interface GRAS. Spacecraft and magnets were modeled together with a simplified mechanical structure supporting the coils. Radiation transport through magnetic fields and materials was simulated for a deep-space mission scenario, considering for the first time the effect of secondary particles produced in the passage of space radiation through the active shielding and spacecraft structures. When modeling the structures supporting the active shielding systems and the habitat, the radiation protection efficiency of the magnetic field is severely decreasing compared to the one reported in previous studies, when only the magnetic field was modeled around the crew. This is due to the large production of secondary radiation taking place in the material surrounding the habitat.


Differential effects of bicarbonate on severe hypoxia- and hypercapnia-induced cardiac malfunctions in diverse fish species.
We tested in six fish species [Pacific lamprey (Lampetra richardsoni), Pacific spiny dogfish (Squalus suckleyi), Asian swamp eel (Monopterus albus), white sturgeon (Acipenser transmontanus), zebrafish (Danio rerio), and starry flounder (Platichthys stellatus)] the hypothesis that elevated extracellular [HCO3-] protects spontaneous heart rate and cardiac force development from the known impairments that severe hypoxia and hypercapnic acidosis can induce. Hearts were exposed in vitro to either severe hypoxia (~ 3% of air saturation), or severe hypercapnic acidosis (either 7.5% CO2 or 15% CO2), which reduced heart rate (in six test species) and net force development (in three test species). During hypoxia, heart rate was restored by [HCO3-] in a dose-dependent fashion in lamprey, dogfish and eel (EC50 = 5, 25 and 30 mM, respectively), but not in sturgeon, zebrafish or flounder. During hypercapnia, elevated [HCO3-] completely restored heart rate in dogfish, eel and sturgeon (EC50 = 5, 25 and 30 mM, respectively), had a partial effect in lamprey and zebrafish, and had no effect in flounder. Elevated [HCO3-], however, had no significant effect on net force of electrically paced ventricular strips from dogfish, eel and flounder during hypoxia and hypercapnia. Only in lamprey hearts did a specific soluble adenylyl cyclase (sAC) inhibitor, KH7, block the HCO3--mediated rescue of heart rate during both hypoxia and hypercapnia, and was the only species where we conclusively demonstrated sAC activity was involved in the protective effects of HCO3- on cardiac function. Our results suggest a common HCO3--dependent, sAC-dependent transduction pathway for heart rate recovery exists in cyclostomes and a HCO3--dependent, sAC-independent pathway exists in other fish species.


At-home and away-from-home dietary patterns and BMI z-scores in Brazilian adolescents.
Away-from-home food intake has been associated with high rates of overweight among children and adolescents. However, there are no studies comparing at-home and away-from-home eating patterns among adolescents. The objective of this paper was to identify at-home and away-from-home dietary patterns among adolescents in Brazil, and to evaluate the relationship between these patterns and body mass index (BMI) z-scores. Data from the Brazilian National Dietary Survey 2008-2009 were analyzed in this cross-sectional study. Dietary intake was assessed by completion of written food records on two non-consecutive days. Five thousand two hundred sixty-six adolescents 10-19 years of age living in urban areas of Brazil were included in the analysis. Thirty-two food groups were examined by factor analysis, stratified by at-home and away-from-home eating. The associations between the food patterns and BMI z-scores were ascertained using linear regression analysis. In general, mean at-home food intake was greater than away-from-home food intake, but the ratio of away-from-home/at-home was greater than 30% for baked and deep-fried snacks, soft drinks, sandwiches, pizza, and desserts, and was lower than 10% for rice and beans. Three main similar dietary patterns were identified both at-home and away-from-home: the "Traditional pattern", the "Bread and Butter pattern" and the "Western pattern"; however, away-from-home patterns encompassed more overall food items. Only the at-home "Western pattern" was positively associated with BMI z-scores (β = 0.0006; p < 0.001). Our results indicate that unhealthy dietary pattern consumed at home is associated to BMI z-score, while away-from-home food consumption is not associated.


Electron-Impact Ionization Cross Sections of Molecules Containing Heavy Elements (Z > 10).
The binary-encounter-Bethe (BEB) theory has been successful for computing electron-impact ionization cross sections of many molecules. For molecules that contain heavy atoms (defined here as atoms with valence principal quantum number n > 2), there are two alternative BEB procedures in the literature. The first involves a kinetic-energy correction for molecular orbitals that are dominated by atomic orbitals with n > 2. The second alternative is to use effective core potentials (ECPs), which were developed for other purposes but yield valence pseudo-orbitals with reduced kinetic energies. In the present study, the results of these two approaches are compared with experimental cross sections for several molecules containing heavy elements. Although both procedures perform well, the ECP results agree somewhat better with experimental measurements. Cross sections are presented for C2Cl6, C2HCl5, C2Cl4, both isomers of C2H2Cl4, CCl4, TiCl4, CBr4, CHBr3, CH2Br2, P2, P4, As2, As4, GaCl, CS2, H2S, CH3I, Al(CH3)3, Ga(CH3)3, hexamethyldisiloxane, and Zn(C2H5)2. Incorrect BEB calculations have been reported in the literature for several of these molecules. As an ancillary result, the dipole polarizability of Zn(C2H5)2 is predicted to be 12.1 Å(3).


Interaction of antiandrogen-androgen receptor complexes with DNA and transcription activation.
Human androgen receptor (hAR) is a ligand-dependent transcription factor that mediates androgen-induced actions on target tissues. Transfection studies in receptor deficient monkey kidney cells CV-1 in culture examine the ability of dihydrotestosterone (DHT) and of the antiandrogens hydroxylflutamide (HO-FLU), cyproterone acetate (Cypro.A) and RU 23908-10 to stimulate or to inhibit the transcription activation of mouse mammary tumor virus-bacterial chloramphenicol acetyltransferase (MMTV-CAT). CV-1 cells cotransfected with wild type hAR (hAR1-910) and MMTV-CAT, were treated with varying concentrations of DHT. DHT stimulated transcription activation of MMTV-CAT gene in a dose-dependent fashion. Cypro.A though only partially, also stimulated the transcription activation of MMTV-CAT. In the absence of steroids, HO-FLU induced the MMTV-CAT transcription in transfectants only 4% above the basal level. RU 23908-10 revealed the least agonistic activity at concentrations between 10 nM and 1 microM. Despite this, 100- to 1000-fold molar excess of all antiandrogens inhibited the agonistic activity of 10 nM DHT in this system. Receptor binding assays confirmed that HO-FLU, Cypro.A and RU 23908-10 competed with [3H]DHT for AR binding with hAR expressed in CV-1 cells. Western blot analysis using AR antipeptide antibodies raised in rabbits revealed the presence of two AR protein bands in extracts prepared from hAR1-910 transfected CV-1 cells. Incubation of labeled synthetic palindromic androgen responsive element (ARE) with the hAR containing CV-1 cell extracts followed by u.v. cross-linking demonstrated the specificity of AR-DNA interaction. Analysis by gel mobility shift assays showed that the interaction of AR-antiandrogen complexes with labeled ARE was specific.


Integration of Metabolome and Transcriptome Reveals the Major Metabolic Pathways and Potential Biomarkers in Response to Freeze-Stress Regulation in Apple (Malus domestica).
Freezing stress is the main factor affecting the normal growth and distribution of plants. The safe overwintering of a perennial deciduous plant is a crucial link to ensuring its survival and yield. However, little is known about the molecular mechanism of its gene regulation metabolites as related to its freeze-tolerance. In order to enhance our comprehension of freeze-tolerance metabolites and gene expression in dormant apple trees, we examined the metabolic and transcriptomic differences between 'Ralls' and 'Fuji', two apple varieties with varying degrees of resistance to freezing. The results of the freezing treatment showed that 'Ralls' had stronger freeze-tolerance than 'Fuji'. We identified 302, 334, and 267 up-regulated differentially accumulated metabolites (DAMs) and 408, 387, and 497 down-regulated DAMs between 'Ralls' and 'Fuji' under -10, -15, and -20 °C treatment, respectively. A total of 359 shared metabolites were obtained in the upward trend modules, of which 62 metabolites were associated with 89 pathways. The number of up-regulated genes accounted for 50.2%, 45.6%, and 43.2% of the total number of differentially expressed genes (DEGs), respectively, at -10, -15, and -20 °C. Through combined transcriptome and metabolome analysis, we identified 12 pathways that included 16 DAMs and 65 DEGs. Meanwhile, we found that 20 DEGs were identified in the phenylpropanoid biosynthesis pathway and its related pathways, involving the metabolism of p-Coumaroyl-CoA, 7, 4'-Dihydroxyflavone, and scolymoside. These discoveries advance our comprehension of the molecular mechanism underlying apple freeze-tolerance and provide genetic material for breeding apple cultivars with enhanced freeze-tolerance.


Monitoring unfractionated heparin therapy: Lack of standardization of anti-Xa activity reagents.
One of the main advantages of using anti-Xa instead of activated partial thromboplastin time in monitoring of unfractionated heparin (UFH) therapy relies on its hypothesized standardization, with a unique therapeutic range defined to be 0.30 to 0.70 IU/mL. The aim of the present study was to compare the inter-reagent agreement of anti-Xa activity. Citrate tubes were obtained from 104 inpatients on UFH. Plasma samples were stored frozen in aliquots at -70°C before being shipped to three accredited coagulation laboratories to be evaluated for anti-Xa activity using their routine assay(s). Pooled normal plasmas spiked with dilutions of the 6th International Standard of UFH to achieve anti-Xa activities up to 1.0 IU/mL were evaluated using the same techniques. In the plasmas from patients on UFH, the median anti-Xa activity ranged from 0.37 IU/mL with one reagent to 0.57 IU/mL with another; results were in between (0.45 IU/mL) using two other reagents. Comparisons of results obtained using the different reagents demonstrated unacceptable bias up to 0.24 IU/mL between some reagents (41% difference). The concordance as whether anti-Xa activities measured using different reagents were within or outside the therapeutic range was between 0.411 and 0.939 (kappa). Similar discrepancy was demonstrated for anti-Xa activities when evaluating normal plasma spiked with the International Standard. A discrepancy of the same order of magnitude was demonstrated in the 2017 External Quality Assessment Program provided by the External Quality Control in Assays and Tests exercises. The reported discrepancy between test results obtained using different anti-Xa assays clearly suggests a lack of standardization of that assay with potentially significant impact on the patients' anticoagulation.


Whole-exome sequencing of a patient with primary central nervous system T-cell lymphoma: Clinicopathological features and genomic profiling.
Primary central nervous system T-cell lymphoma (T-PCNSL) is a rare neoplasm, and its underlying genetic features are poorly understood. Herein, we present the case of a 64-year-old man with T-PCNSL who presented with left-side limb weakness. Brain magnetic resonance imaging revealed a right parietal space-occupying lesion. Immunohistochemically, the tumor was positive for CD3, CD4, CD5, CD8, and CD56, and the Ki-67 labeling index was approximately 20%. These pathological features are consistent with those of T-cell lymphoma. Whole exome sequencing was performed, and we found a variant in the ACSS3 gene that could be related to disease pathogenesis. Our findings may help advance our understanding of the molecular pathogenesis of T-PCNSL. Further molecular analysis of such cases could help to improve adjuvant molecular diagnostic methods and targeted therapies for T-PCNSL.


Secretory endometrium associated with breakthrough bleeding in estrogen-treated postmenopausal women.
Paradoxical secretory changes are described in benign endometria curetted for breakthrough bleeding in postmenopausal women on cyclic low dosage Premarin therapy. This purely histologic study, though favoring progesterone mediation, provides no definitive answer to the problem of pathogenesis. Future correlative morphologic and endocrine investigations are clearly indicated.


What do prescribers think of biosimilars?
Until recently, prescribers had to deal with generics, considered to be simple molecules that are easy to copy. But as discussed in this paper, the biodisponibility of generics remains a source of uncertainty. And now there are biosimilars, limited for the time being in the cancer setting to granulocyte-colony stimulating factors (G-CSFs) and epoetins. Soon there will be biosimilar monoclonal antibodies with anticancer activity. Prescribers will ask, as they did for generics, if such drugs have the same activity as originators, if their safety profile is the same, if quality of the production process is guaranteed. Prescribers will want to know if their patients are indeed receiving the prescribed product, and not another. Finally prescribers will want to check that the lower cost of biosimilars will allow them to adhere to international guidelines. This should benefit patients and the community.


Applying the adverse outcome pathway concept for assessing non-monotonic dose responses: biphasic effect of bis(2-ethylhexyl) phthalate (DEHP) on testosterone levels.
Male reproduction is one of the primary health endpoints identified in rodent studies for some phthalates, such as DEHP (Bis(2-ethylhexyl) phthalate), DBP (Dibutyl phthalate), and BBP (Benzyl butyl phthalate). The reduction in testosterone level was used as an intermediate key event for grouping some phthalates and to establish a reference point for risk assessment. Phthalates, and specifically DEHP, are one of the chemicals for which the greatest number of non-monotonic dose responses (NMDRs) are observed. These NMDRs cover different endpoints and situations, often including testosterone levels. The presence of NMDR has been the subject of some debate within the area of chemical risk assessment, which is traditionally anchored around driving health-based guidance values for apical endpoints that typically follow a clear monotonic dose-response. The consequence of NMDR for chemical risk assessment has recently received considerable attention amongst regulatory agencies, which confirmed its relevance particularly for receptor-mediated effects. The present review explores the relationship between DEHP exposure and testosterone levels, investigating the biological plausibility of the observed NMDRs. The Adverse Outcome Pathway (AOP) concept is applied to integrate NMDRs into Key Event Relationships (KERs) for exploring a mechanistic understanding of initial key events and possibly associated reproductive and non-reproductive adverse outcomes.


Tumor tissue characterization evaluating the luciferase activity under the control of a hsp70 promoter and MR imaging in three tumor cell lines.
We investigated the luciferase activity under the control of a hsp70 promoter and MR imaging for three tumor cell lines. Three tumor cell lines, SCCVII, NIH3T3 and M21 were transfected with a plasmid containing the hsp70 promoter fragment and the luciferase reporter gene and grown in mice. Bioluminescence imaging of the tumors was performed every other day. MR imaging, pre- and post-contrast T1-wt SE, T2-wt FSE, Diffusion-wt STEAM-sequence, T2-time determination were obtained on a 1.5-T GE MRI scanner at a tumor size of 600-800 mm(3) and 1400-1600 mm(3). Comparing the different tumor sizes the luciferase activity of the M21 tumors increased about 149.3%, for the NIH3T3 tumors about 47.4% and for the SCCVII tumors about 155.8%. Luciferase activity of the M21 tumors (r=0.82, p<0.01) and the SCCVII tumors (r=0.62, p=0.03) correlated significant with the diffusion coefficient. In the NIH3T3 tumors the best correlation between the luciferase activity and the MRI parameter was seen for the SNR (T2) values (r=0.78, p<0.01). The luciferase activity per mm(3) tumor tissue correlated moderate with the contrast medium uptake (r=0.55, p=0.01) in the M21 tumors. In the NIH3T3 and SCCVII tumors a negative correlation (r=-0.78, p<0.01, respectively, r=-0.49, p=0.02) was found with the T2 time. Different tissue types have different luciferase activity under the control of the same hsp70 promoter. The combination of MR imaging with bioluminescence imaging improves the characterization of tumor tissue giving better information of this tissue on the molecular level.


Modulatory effect of opioid ligands on status epilepticus and the role of nitric oxide pathway.
Epilepsy is a chronic disorder that causes unprovoked, recurrent seizures. Status epilepticus (SE) is a medical emergency associated with significant morbidity and mortality. Morphine has been the cornerstone of pain controlling medicines for a long time. In addition to the analgesic and opioid responses, morphine has also revealed anticonvulsant effects in different epilepsy models including pentylenetetrazole (PTZ)-induced seizures threshold. Some authors suggest that nitric oxide (NO) pathway interactions of morphine explain the reason for its pro or anticonvulsant activities. To induce SE, injection of a single dose of lithium chloride (127 mg/kg, intraperitoneal (i.p.)) 20 h before pilocarpine (60 mg/kg, i.p.) was used. Administration of morphine (15 mg/kg, i.p.) inhibited the SE and decreased the mortality in rats when injected 30 min before pilocarpine. On the other hand, injection of L-NG-nitro arginine methyl ester (L-NAME, a nonselective NO synthase (NOS) blocker; 10 mg/kg, i.p.), 7-nitroindazole (7-NI, a neuronal NOS (nNOS) blocker; 30 mg/kg, i.p.), and aminoguanidine (AG, an inducible NOS (iNOS) blocker; 50 mg/kg, i.p.) 15 min before morphine, significantly reversed inhibitory effect of morphine on SE. Subsequently, measurement of nitrite metabolite levels in the hippocampus of SE-induced rats displayed high levels of nitrite metabolite for the control group. However, after injection of morphine in SE-induced rats, nitrite metabolite levels reduced. In conclusion, these findings demonstrated that NO pathway (both nNOS and iNOS) interactions are involved in the anticonvulsant effects of morphine on the SE signs and mortality rate induced by lithium-pilocarpine in rats.


Acute Hyperglycemia Is Associated with Immediate Brain Swelling and Hemorrhagic Transformation After Middle Cerebral Artery Occlusion in Rats.
Hemorrhagic transformation occurs in as many as 48 % of stroke patients and is a major contributor to post-insult morbidity and mortality. Experimental models of hemorrhagic transformation are utilized for understanding the mechanisms behind its development, as well as for investigating potential therapeutics for prevention and reduction of bleeding. Thoroughly studying animal models of hemorrhagic transformation is critically important for testing novel treatments. Thus far, no study has examined the progression of brain swelling and hemorrhagic transformation after transient middle cerebral artery occlusion (MCAO). Herein, we investigate the development of infarction, brain swelling, and hemorrhagic transformation following MCAO in hyperglycemic rats. Twenty-five Sprague-Dawley rats were subjected to either 1.5 h of MCAO or sham surgery 15 min after induction of hyperglycemia. Animals were sacrificed at 0.25, 1, 3, or 24 h after reperfusion for measurement of infarct volume, brain swelling, and hemoglobin volume. Within 15 min of reperfusion, the infarct volume was significantly larger than in sham animals and did not increase in size over the 24 h. However, both brain swelling and hemorrhagic transformation, which began immediately after reperfusion, increase over 24 h after reperfusion.


Lunar biological effects and the magnetosphere.
The debate about how far the Moon causes biological effects has continued for two millennia. Pliny the Elder argued for lunar power "penetrating all things", including plants, fish, animals and humans. He also linked the Moon with tides, confirmed mathematically by Newton. A review of modern studies of biological effects, especially from plants and animals, confirms the pervasive nature of this lunar force. However calculations from physics and other arguments refute the supposed mechanisms of gravity and light. Recent space exploration allows a new approach with evidence of electromagnetic fields associated with the Earth's magnetotail at full moon during the night, and similar, but more limited, effects from the Moon's wake on the magnetosphere at new moon during the day. The disturbance of the magnetotail is perhaps shown by measurements of electric fields of up to 16V/m compared with the usual <1V/m, suggesting the possibility of weak biological effects on some sensitive organisms. Similar intensities found in sferics, geomagnetic storms, aurora disturbance, sensations of a 'presence' and pre-seismic electromagnetic radiation are known to affect animals and 10-20% of the human population. There is now evidence for mechanisms such as calcium flux, melatonin disruption, magnetite and cryptochromes. Both environmental and receptor variations explain confounding factors and inconsistencies in the evidence. Electromagnetic effects might also account for some evolutionary changes. Further research on lunar biological effects, such as acute myocardial infarction, could help the development of strategies to reduce adverse effects for people sensitive to geomagnetic disturbance.


Antioxidant, cytoprotective and antibacterial effects of Sea buckthorn (Hippophae rhamnoides L.) leaves.
The present study was carried out to investigate the antioxidant, cytoprotective and antibacterial effects of aqueous and hydroalcoholic extracts of Hippophae rhamnoides L. (Sea buckthorn) (SBT) leaves by using various in vitro systems and analysis of marker compounds by reverse phase-high performance liquid chromatography (RP-HPLC). The chemical composition of the leaf extracts was quantified by colorimetric reaction in terms of total phenol and flavonoids contents. Further, some of its bioactive phenolic constituents, such as quercetin-3-O-galactoside, quercetin-3-O-glucoside, kaempferol and isorhamnetin were also quantified in both SBT leaf extracts by RP-HPLC. The SBT leaf extracts exhibited potent antioxidant activity determined by 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), 2,2-diphenyl-1-picryl-hydrazyl (DPPH) and ferric reducing antioxidant power (FRAP) assays. Further, both extracts were observed to have cytoprotective activity against hydrogen peroxide and hypoxanthine-xanthine oxidase induced damage to BHK-21 cell line. The SBT leaf extracts showed growth inhibiting effect against Bacillus cereus, Pseudomonas aeruginosa, Staphylococcus aureus and Enterococcus faecalis. These observations suggest that aqueous and hydroalcoholic extracts of Sea buckthorn leaves have marked antioxidant, cytoprotective and antibacterial activities.


Less invasive Achilles tendon reconstruction.
The optimal management of chronic ruptures of the Achilles tendon is surgical reconstruction. Reconstruction of the Achilles tendon using peroneus brevis has been widely reported. Classically, these procedures involve relatively long surgical wounds in a relatively hypovascular area which is susceptible to wound breakdown. We describe our current method of peroneus brevis reconstruction for the Achilles tendon using two para-midline incisions. This technique allows reconstruction of the Achilles tendon using peroneus brevis preserving skin integrity over the site most prone to wound breakdown, and can be especially used to reconstruct the Achilles tendon in the presence of previous surgery.


Peri-implant stress correlates with bone and cement morphology: Micro-FE modeling of implanted cadaveric glenoids.
Aseptic loosening of cemented joint replacements is a complex biological and mechanical process, and remains a clinical concern especially in patients with poor bone quality. Utilizing high resolution finite element analysis of a series of implanted cadaver glenoids, the objective of this study was to quantify relationships between construct morphology and resulting mechanical stresses in cement and trabeculae. Eight glenoid cadavers were implanted with a cemented central peg implant. Specimens were imaged by micro-CT, and subject-specific finite element models were developed. Bone volume fraction, glenoid width, implant-cortex distance, cement volume, cement-cortex contact, and cement-bone interface area were measured. Axial loading was applied to the implant of each model and stress distributions were characterized. Correlation analysis was completed across all specimens for pairs of morphological and mechanical variables. The amount of trabecular bone with high stress was strongly negatively correlated with both cement volume and contact between the cement and cortex (r = -0.85 and -0.84, p < 0.05). Bone with high stress was also correlated with both glenoid width and implant-cortex distance. Contact between the cement and underlying cortex may dramatically reduce trabecular bone stresses surrounding the cement, and this contact depends on bone shape, cement amount, and implant positioning.


Optimal conditions for protein synthesis in incubated slices of rat brain.
Optimal conditions for protein synthesis in incubated slices of rat brain were determined to be: thickness 0.3 mm under air (for newborn 0.4-0.6 mm) or 0.5 mm under oxygen; temperature, 35-36 degrees C; hepes (N-2-hydroxyethylpiperazine-N'-2-ethane sulfonic acid) buffer; K+, 6-8 mM; Ca2+, 2-3 mM. Though maximum incorporation was found with a Na+ concentration of 110-12- mM. Though maximum incorporation was found with a Na+ concentration of 110-120mM, this requirement appears to be partly osmotic. The Na+ concentration may be reduced to 80 mM without inhibition of incorporation provided adjustment is made for osmotic balance. Mg2+. Optimal pH was 7.2-7.4. The rate of protein synthesis in this medium is 0.08-0.09% replacement of the protein amino acid/h in slices from adults and 1.6%/h in slices from 3-day-old rats. Thus slices from adults synthesize protein at 10-20% of the in vivo rate whereas slices at 3-day-old brainincorporate amino acid at 70-80% of the in vivo rate for young rats.


A controlled evaluation of acceptance and commitment therapy plus habit reversal for trichotillomania.
This randomized trial compared a combined Acceptance and Commitment Therapy/Habit Reversal Training (ACT/HRT) to a waitlist control in the treatment of adults with trichotillomania (TTM). Twenty-five participants (12 treatment and 13 waitlist) completed the trial. Results demonstrated a significant reduction in hair pulling severity, impairment ratings, and hairs pulled, along with significant reductions in experiential avoidance and both anxiety and depressive symptoms in the ACT/HRT group compared to the waitlist control. Reductions generally were maintained at a 3-month follow-up. Decreases in experiential avoidance and greater treatment compliance were significantly correlated with reductions in TTM severity, implying that targeting experiential avoidance may be useful in the treatment of TTM. Other implications and suggestions for future research are noted.