Elevated Norepinephrine may be a Unifying Etiological Factor in the Abuse of a Broad Range of Substances: Alcohol, Nicotine, Marijuana, Heroin, Cocaine, and Caffeine.
A wide range of commonly abused drugs have effects on the noradrenergic neurotransmitter system, including alterations during acute intoxication and chronic use of these drugs. It is not established, however, that individual differences in noradrenergic signaling, which may be present prior to use of drugs, predispose certain persons to substance abuse. This paper puts forth the novel hypothesis that elevated noradrenergic signaling, which may be raised largely due to genetics but also due to environmental factors, is an etiological factor in the abuse of a wide range of substances, including alcohol, nicotine, marijuana, heroin, cocaine, and caffeine. Data are reviewed for each of these drugs comprising their interaction with norepinephrine during acute intoxication, long-term use, subsequent withdrawal, and stress-induced relapse. In general, the data suggest that these drugs acutely boost noradrenergic signaling, whereas long-term use also affects this neurotransmitter system, possibly suppressing it. During acute withdrawal after chronic drug use, noradrenergic signaling tends to be elevated, consistent with the observation that norepinephrine lowering drugs such as clonidine reduce withdrawal symptoms. Since psychological stress can promote relapse of drug seeking in susceptible individuals and stress produces elevated norepinephrine release, this suggests that these drugs may be suppressing noradrenergic signaling during chronic use or instead elevating it only in reward circuits of the brain. If elevated noradrenergic signaling is an etiological factor in the abuse of a broad range of substances, then chronic use of pharmacological agents that reduce noradrenergic signaling, such as clonidine, guanfacine, lofexidine, propranolol, or prazosin, may help prevent or treat drug abuse in general.


Determinants of atrial natriuretic factor secretion in dogs expanded with isotonic saline or colloid solutions.
Through increments in blood volume and atrial pressure are thought to be the primary stimuli for ANF secretion, plasma levels of this peptide do not always behave as a simple function of volume status. To outline the relationship between the latter and cardiac ANF release, we used five different volume-expansion protocols in anesthetized dogs. A stepwise expansion of plasma volume (PV) was achieved by two consecutive infusions: 0.9% saline followed or preceded by 4 or 25% bovine serum albumin (BSA), 4 or 25% dextran (Dx), or homologous plasma. Saline expansion led to a two- to four-fold increase in arterial plasma ANF level in all five protocols. Both 4 and 25% BSA caused no or very modest increase in plasma ANF, while all other colloid expanders caused the expected ANF release. In all protocols, plasma ANF closely correlated with central venous pressure (CVP). BSA expansion was the only protocol with no correlation between PV and ANF release. Changes in serum Ca2+ could not explain this finding. During BSA expansion, the lack of atrial response was related to the absence of increment (or even fall) in CVP despite the expanded PV. Similarly, urinary Na+ excretion was correlated both with CVP and ANF level but not with PV in BSA expansion. When the dogs were depleted of histamine before BSA infusion, the atrial secretory response was restored, suggesting that this colloid was associated with augmented capillary leakiness and vascular fluid efflux. These results show that the expansion of PV leads neither to ANF release nor to Na+ excretion if it is not accompanied by an expanded central blood volume with elevated atrial pressure.


Estimating the time-varying reproduction number of COVID-19 with a state-space method.
After slowing down the spread of the novel coronavirus COVID-19, many countries have started to relax their confinement measures in the face of critical damage to socioeconomic structures. At this stage, it is desirable to monitor the degree to which political measures or social affairs have exerted influence on the spread of disease. Though it is difficult to trace back individual transmission of infections whose incubation periods are long and highly variable, estimating the average spreading rate is possible if a proper mathematical model can be devised to analyze daily event-occurrences. To render an accurate assessment, we have devised a state-space method for fitting a discrete-time variant of the Hawkes process to a given dataset of daily confirmed cases. The proposed method detects changes occurring in each country and assesses the impact of social events in terms of the temporally varying reproduction number, which corresponds to the average number of cases directly caused by a single infected case. Moreover, the proposed method can be used to predict the possible consequences of alternative political measures. This information can serve as a reference for behavioral guidelines that should be adopted according to the varying risk of infection.


[Influence of genetic mutations on clinical presentation of subretinal neovascularization. Report 1: The impact of CFH and IL-8 genes polymorphism].
Genetic analysis was performed in patients with subretinal neovascularization (CNV). The results showed significant association of CFH (compliment factor H) gene polymorphism with increase (rs1061170, rs514943 and rs380390) or decrease (rs529825, rs7524776, rs1831281, rs2274700, rs1576340, rs12144939, rs7540032) of CNV development risk. The incidence of IL-8 gene mutation was significantly (p = 0.008) higher in patients after chorioretinitis. Apparently -125 > A polymorphism in patients with chorioretinitis increases risk of CNV development, thus promoting raise of proangiogenic factors concentration in eyes with inflammatory background. The clinical presentation in patients with AMD and myopic disease associated with (-125) A mutation of promoter region of IL-8 gene was similar to that of patients with chorioretinitis. The features are the following: focal pattern, no drusen and RPE detachment, predominantly classic form of CNV (without occult pattern), formation of well-organized newly developed vessels.


The effect of fish oil on blood pressure in mild hypertensive subjects: a randomized crossover trial.
We conducted a double-blind, crossover trial with 18 healthy, untreated mildly hypertensive subjects to test the effect on blood pressure of 6 or 12 g fish oil/d (50% n-3 fatty acids) as compared with an olive oil placebo. Blood pressure was measured every 6 wk in the clinic and three times daily by subjects using a semiautomated device in their homes. Compliance was determined biochemically. No significant changes in home or clinic blood pressure measurements were noted for either dose after 6 or 12 wk of treatment. Clinic blood pressure after 12 g fish oil/d was slightly lower than after placebo treatment by -0.8/-0.4 mm Hg [95% CI: systolic blood pressure (-4.4, +2.8); diastolic blood pressure (-3.2, +2.4)]. Blood pressure changes were not correlated with compliance, baseline dietary fish consumption, or blood pressure. Moderate doses of fish oil did not have a substantial effect on blood pressure. We conclude that fish oil is not a practical treatment for mild hypertension.


In memoriam Bernard Strehler--genomic instability in ageing: a persistent challenge.
Genomic instability comprises a broad spectrum of mutational alterations in the genome, such as point mutations in DNA, microsatellite expansions or contractions, amplifications and deletions of DNA sequences, gene rearrangements and structural or numerical chromosomal aberrations. A substantial body of data demonstrates an increase of genomic instability during normal ageing. This includes cytogenetic changes; loss of rDNA; formation of extrachromosomal circular DNA species; loss of telomeric repeats; increased microsatellite instability; as well as point mutations and deletions in global nuclear and mitochondrial DNA. Evidence has accumulated supporting a causative role of genomic instability in ageing. Genomic instability can be counteracted by a number of proteins including antioxidant enzymes, the WRN protein (deficient in Werner syndrome), telomerase, poly(ADP-ribose) polymerase-1 and a range other others, as well as by multi-protein systems such as DNA mismatch repair, base-excision repair and nucleotide-excision repair. Important research tasks for the future will be to elucidate how and what extent the various expressions of genomic instability contribute to the ageing process and to understand the molecular mechanisms and regulation of the above factors and pathways involved in limiting the induction of ageing-associated genomic instability.


Changes in vascular porosity and joint blood flow during development of collagen induced arthritis in the rat. Modulation by indomethacin and L-NAME.
To investigate changes in regional blood flows (RBF) and vascular porosity during the early phase of the autologous collagen II induced arthritis model (CIA) in rats and the possible influence of indomethacin and nitric oxide (NO) synthase on these variables. RBF was measured with the microsphere method and vascular porosity by determination of extravasation of radiolabeled albumin. Onset of arthritis was associated with a rapid increase in vascular porosity in the knee. In ankles and paws this increase was somewhat slower in onset, but progressed during the course of the study. Acute treatment with indomethacin reduced albumin extravasation in the knees, but had no effect in the ankles or paws. Similarly, chronic indomethacin treatment also had no effect on the arthritic score. Serum levels of nitrite/nitrate did not change markedly during the development of CIA, and NO synthase inhibition did not affect the vascular porosity. The changes in RBF were relatively modest. In most tissues the total RBF increased with increasing tissue weight. Pretreatment with indomethacin reduced RBF in the paws, but not in the periarticular tissue. The development of CIA is characterized by a marked rise in vascular porosity in affected joints, but the changes in RBF are much smaller and nonpersistent. The leakiness seems to be insensitive to the modulation of RBF and the responses in the knee show different characteristics compared to those in the ankle/paw.


Why Can't We Accurately Predict Others' Decisions? Prediction Discrepancy in Risky Decision-Making.
Individuals often fail to accurately predict others' decisions in a risky environment. In this paper, we investigate the characteristics and causes of this prediction discrepancy. Participants completed a risky decision-making task mixed with different domains (gain vs. loss) and probabilities (small vs. large), with some participants making decisions for themselves (the actor) and the others predicting the actors' decisions (the predictor). The results demonstrated a prediction discrepancy: predictions were more risk-averse than the actual decisions over small-probability gains and more risk-seeking over large-probability gains, while these patterns were reversed in the loss domain. Reported and predicted levels of emotional stimulation revealed a pattern that is consistent with the notion of risk-as-feelings and empathy gaps. Mediation analysis provided strong evidence that such prediction discrepancy is driven mainly by the predictor's underestimate of the intensity (not the impact) of the actor's emotional state.


In silico patent searching reveals a new cannabinoid receptor.
Increasing evidence suggests that some cannabinoids mediate their effects independently of the known cannabinoid CB(1) and CB(2) receptors. Two recently published patents indicate that several cannabinoid receptor ligands also bind to the orphan G-protein-coupled receptor GPR55. This receptor is reported to be expressed in several tissues and might function in lipid or vascular biology. Thus, GPR55 might represent a new cannabinoid receptor.


Evaluating oxygen delivery and oxygen utilization with mixed venous oxygen saturation monitoring: a case study approach.
Three cases studies are presented to demonstrate clinical application of mixed venous oxygen saturation (SvO2) monitoring in critical care nursing practice. Examples of critically ill patients are used to demonstrate how SvO2 monitoring can be used in clinical practice to reflect an imbalance between oxygen delivery and oxygen utilization. In the first case, the patient had a problem with oxygen delivery. Continuous SvO2 data aided nurses in guiding, adjusting, and assessing therapy. The second case demonstrates how SvO2 monitoring can provide an early sign of a life-threatening complication. The final case is one in which the patient had a problem with oxygen utilization. In all the cases, continuous SvO2 data provided important information about the balance between oxygen delivery and oxygen utilization.


Photoinhibition Resistance in the Red Alga Porphyra perforata: The Role of Photoinhibition Repair.
Photoinhibition resistance exhibited by the high intertidal red alga Porphyra perforata relative to its subtidal congener Porphyra nereocystis was examined using the protein synthesis inhibitor chloramphenicol to separate the damage and repair components of photoinhibition. Under photoinhibitory conditions, the rates of both damage to and replacement of photoinhibition-sensitive proteins was much higher in P. nereocystis than in P. perforata. Thus, photoinhibition resistance in P. perforata appears to be due to a reduced rate of photoinhibition damage rather than to an accelerated rate of photoinhibition repair. Reduction of photoinhibition damage in P. perforata may be by means of biophysical processes which increase the radiationless decay of excitation to heat in photosystem II. Alternatively, the photoinhibition-sensitive proteins in P. perforata may have slight structural alterations that improve their stability or they may be protected by enzyme systems that quench radicals formed by overexcitation of photosystem II. Reduction of the damage component of photoinhibition is a reasonable way to limit photoinhibition in P. perforata during the severe desiccation and exposure to full sun that occur simultaneously during daily low tides, conditions under which the protein synthesis required for photoinhibition repair could not occur.


In vivo transplantation of stem cells with a genipin linked scaffold for tracheal construction.
To establish the procedures of genipin-linked scaffold for in situ tracheal reconstruction in a rabbit model, and to demonstrate whether stem cells can be further differentiated in the bioreactor in vivo. It will further provide an experimental and theoretical foundation for clinical application. Previously, in vitro evaluation proved the detergent–enzymatic method effectively removed stromal epithelial cells, and the number of nuclei was reduced significantly (p < 0.05). The content of type II collagen was not statistically reduced (p > 0.05). Plasmids with green fluorescence protein were transfected into 293T cells, and these cells subsequently synthesized lentivirus with green fluorescence protein that could infect other cells. After in vivo experiments, macroscopic specimen observation and hematoxylin and eosin staining comparison showed that the genipin cross-linked decellularized scaffold had low immunological rejection. Blood routine proved the progenitor cells (such as mononuclear cells) can be mobilized from the bone marrow by the growth factors, to allow their circulation into the peripheral blood. The immunohistochemistry of Type II collagen after surgery showed the expression level of bone marrow mesenchymal stem cells transplantated group was statistically higher than the autologous transplantated group (p < 0.05). The fluorescences of Bone marrow mononuclear cells (BMNCs) were traced after the specimens harvested. It successfully demonstrated that the procedures combining stem cells with the genipin cross-linked decellularized scaffold could apply to in situ airway construction. Compared to bone marrow mesenchymal stem cells, BMNCs can also be used to achieve chondrocyte differentiation; this procedure will avoid in vitro cell culture, shortening the time and economic costs.


Dermoscopy and in vivo reflectance confocal microscopy of a congenital nevus of the nipple.
We report a 26-year-old male with a 4 mm diameter, asymmetric, irregularly pigmented and bordered, brown maculopapular lesion on the right nipple present since childhood with enlargement of the lesion within the last 3 months. Dermoscopy revealed a global globular pattern with the presence of focally light brown globules and irregular black globules in its centre. In vivo reflectance confocal microscopy (RCM) revealed dense junctional and dermal melanocytic nests of different sizes and shapes that appeared as sharply demarcated round to oval reflective structures; cellular outlines of single melanocytes were not always detected. In the centre of the lesion within the upper dermis, irregularly shaped, homogeneously reflecting structures were observed. As a clear differentiation between clusters of melanophages and melanocytic nests could not be made with certainty, an excisional biopsy was performed to establish the diagnosis of compound nevus with features of congenital nevus. Therefore, to prove that dermoscopic globules correlated with melanophages, the correlation between dermoscopic RCM and histopathology was necessary.


Evaluation of I-TAC as a potential early plasma marker to differentiate between critical and non-critical COVID-19.
The COVID-19 pandemic has led to significant global health and economic consequences. There is an unmet need to define a molecular fingerprint of severity of the disease that may guide an early, rational and directed intervention preventing severe illness. We collected plasma from patients with moderate (nine cases), severe (22 cases) and critical (five cases) COVID-19 within three days of hospitalization (approximately one week after symptom onset) and used a cytokine antibody array to screen the 105 cytokines included in the array. We found that I-TAC, IP-10, ST2 and IL-1ra were significantly upregulated in patients with critical disease as compared to the non-critical (moderate and severe combined). ELISA further quantified I-TAC levels as 590.24±410.89, 645.35±517.59 and 1613.53±1010.59 pg/ml in moderate, severe and critical groups, respectively. Statistical analysis showed that I-TAC levels were significantly higher in patients with critical disease when compared with moderate (p = 0.04), severe (p = 0.03) or the combined non-critical (p = 0.02) group. Although limited by the low sample numbers, this study may suggest a role of I-TAC as a potential early marker to discriminate between critical and non-critical COVID-19 cases. Such knowledge is urgently needed for appropriate allocation of resources and to serve as a platform for future research towards early interventions that could mitigate disease severity and save lives.


Facile and efficient sulfenylation method using quinone mono-O,S-acetals under mild conditions.
A novel sulfenylation method induced by aromatization of quinone mono-O,S-acetals is described. These sulfenylation reagents readily react with silyl enolethers or electron rich aromatic compounds to give sulfenylation products under mild conditions. In particular, O,S-acetal 2j, which possesses a pentafluorophenylthio function, is the most effective reagent from the standpoint of the adaptability for various substrates.


Oral Antibiotic Treatment Options for Acne Vulgaris.
Acne vulgaris is the most common dermatological disease in the United States, affecting up to 85 percent of teenagers. While the American Academy of Dermatology has established guidelines regarding acne treatment in general, the variability among acne treatments, even within a given class, prevents establishment of a straightforward regimen. For example, moderate to severe acne is generally treated with an oral antibiotic, although several options are available-both across and within antibiotic classes. The aim of this review is to report the efficacy and safety data available for commonly prescribed oral antibiotics. While there are currently no data to support superiority of one drug over another, there are substantial differences in safety profiles and brand-specific features that may make one antibiotic preferable over another.


Diagnosis and Management of Giant Esophageal Fibrovascular Polyp With Hypopharyngeal Pedicle.
Background: Fibrovascular polyps (FVPs) with hypopharyngeal pedicles (hFVPs) are the rare intraluminal benign tumours of the upper aerodigestive tract, and their accurate diagnosis and optimal management are challenging. Purpose: The present retrospective study attempted to explore the optimal diagnosis and treatment of hFVPs. Research Design: The clinical records of 2 patients with giant, irregularly shaped hFVPs, who underwent several failed surgical procedures after inaccurate diagnosis, were reviewed. Finally, the patients were correctly diagnosed and successfully treated at Capital Medical University Beijing Friendship Hospital in different years, 2018 and 2020. Results: Case 1 was of a 43-year-old woman with 2 months of progressive dysphagia. Gastroenterologists overlooked the origin of her FVP, and decided to sever its narrowest point in the oesophagus through endoscopy. However, upon unsuccessful removal of the mass, a gastrotomy procedure was performed to extract the mass 7 days later. Symptoms recurred 3 months after the treatment, and a fibreoptic laryngoscopy confirmed hFVP in the patient at our department. A transcervical approach was used to sever the hypopharyngeal pedicle, achieve haemostasis and remove the oesophageal tumour. No recurrence was detected during the 2-year follow-up period after the treatment. Case 2 was of a 32-year-old man with dysphagia who had previously undergone transthoracic and transcervical oesophagotomy procedures within a gap of 3 months for the removal of FVP causing dysphagia. The hypopharyngeal pedicle was not diagnosed in the patient. The symptoms of dysphagia recurred 4 years after the treatment, and a fibreoptic laryngoscope confirmed hFVP at our department. The tumour was removed successfully through the transcervical approach. No recurrence was detected during the 6-months follow-up after surgery. Conclusion: In conclusion, the transcervical approach is suitable for achieving haemostasis and removing giant, irregularly shaped hFVPs.


Characterization of the retinoblastoma binding proteins RBP1 and RBP2.
The retinoblastoma gene product, pRB, regulates cell proliferation by binding to and inhibiting the activity of key growth promoting proteins. Several cellular proteins have been shown to bind directly to pRB and the genes encoding a number of them have been isolated. The protein product of one of these genes is the transcription factor E2F. We have now isolated cDNA clones that contain the full-length coding sequence of two other proteins, RBP1 and RBP2, cloned originally by their interaction with pRB. The products of the RBP1 and RBP2 genes are ubiquitously expressed, large (200 kDa for RBP1 and 195 kDa for RBP2) nuclear phosphoproteins with structural motifs that suggest a role in transcriptional regulation. In addition we have been able to identify complexes of pRB and RBP1 in vivo that are dissociated in the presence of purified human papillomavirus E7 protein.


Inhalational induction with "vasoparalytic" sevoflurane: are we "hyperoxygenating" while anesthetizing developing brains? A case series discussion.
The concerns for hyperoxia-related brain tissue injury are well known to the medical community. The cerebro-vasodilatory properties of sevoflurane may create relative cerebral tissue "hyperoxia" during inhalational induction as compared to a propofol-based intravenous induction of anesthesia. The objective for this case series discussion was to identify any differences in cerebral tissue oxygenation secondary to induction of anesthesia with sevoflurane versus propofol. METHODS/STUDY PROCEDURES: After institutional review board approval, the computer data of tissue cerebral oximetry of pediatric patients (1-18 years age group) undergoing non-cardiac surgeries was comparatively analyzed for changes over time between the groups of children who received sevoflurane induction versus propofol induction of anesthesia. "Hyperoxia" ("hyperoxygenation") was defined as significant percent changes from the baseline values as recorded in tissue cerebral oximetry. In this case series, seven patients underwent inhalational (INH) induction with high concentrations (8%) sevoflurane with nitrous oxide in 33% oxygen and four patients underwent intravenous (i.v.) induction with 2 mg/kg propofol and nitrous oxide in 33% oxygen. As compared to propofol, significant cerebral tissue "hyperoxia" occurred with sevoflurane induction (p = 0.003). This did not resolve over time. As compared to intravenous induction with propofol, inhalational induction with "vasoparalytic" sevoflurane "hyperoxygenates" developing brains. This observation requires validation in larger trials to conclude appropriate effect on our practice of pediatric anesthesia and pediatric patient safety under anesthesia.


Effects of low birth weight in 8- to 13-year-old children: implications in endothelial function and uric acid levels.
Low birth weight has been associated with an increased incidence of adult cardiovascular disease. Endothelial dysfunction and high levels of serum uric acid are associated with hypertension. In this study, we have determined whether uric acid is related to blood pressure and vascular function in children with low birth weight. We evaluated vascular function using high-resolution ultrasound, blood pressure, and uric acid levels in 78 children (35 girls, 43 boys, aged 8 to 13 years). Increasing levels of uric acid and systolic blood pressure were observed in children with low birth weight. Birth weight was inversely associated with both systolic blood pressure and uric acid; on the other hand, uric acid levels were directly correlated with systolic blood pressure in children of the entire cohort. Low birth weight was associated with reduced flow-mediated dilation (r=0.427, P<0.001). Because the children with low birth weight had elevated uric acid as well as higher systolic blood pressure levels, we evaluated the correlation between these variables. In the low birth weight group, multiple regression analysis revealed that uric acid (beta=-2.886; SE=1.393; P=0.040) had a graded inverse relationship with flow-mediated dilation, which was not affected in a model adjusting for race and gender. We conclude that children with a history of low birth weight show impaired endothelial function and increased blood pressure and uric acid levels. These findings may be early expressions of vascular compromise, contributing to susceptibility to disease in adult life.


Osteogenic Induction with Silicon Hydroxyapatite Using Modified Autologous Adipose Tissue-Derived Stromal Vascular Fraction: In Vitro and Qualitative Histomorphometric Analysis.
Large bone defects requiring invasive surgical procedures have long been a problem for orthopedic surgeons. Despite the use of autologous bone grafting, satisfactory results are often not achieved due to associated limitations. Biomaterials are viable alternatives and have lately been used in association with Stromal Vascular Fraction (SVF), stem cells, and signaling factors for bone tissue engineering (BTE). The objective of the current study was to assess the biocompatibility of Silicon Hydroxyapatite (Si-HA) and to improve osteogenic potential by using autologous adipose-derived SVF with Si-HA in a rabbit bone defect model. Si-HA granules synthesized using a wet precipitation method were used. They were characterized using scanning electron microscopy (SEM), Fourier transform infrared (FTIR), and X-ray diffraction (XRD). A hemolysis assay was used to assess the hemolytic effects of Si-HA, while cell viability was assessed through Alamar Blue assay using MC3T3 mouse osteoblasts. The osteogenic potential of Si-HA both alone and with enzymatically/non-enzymatically-derived SVF (modified) was performed by implantation in a rabbit tibia model followed by histomorphometric analysis and SEM of dissected bone after six weeks. The results showed that Si-HA granules were microporous and phase pure and that the addition of Silicon did not influence Si-HA phase composition. Si-HA granules were found to be non-hemolytic on the hemolysis assay and non-toxic to MC3T3 mouse osteoblasts on the Alamar Blue assay. Six weeks following implantation Si-HA showed high biocompatibility, with increased bone formation in all groups compared to control. Histologically more mature bone was formed in the Si-HA implanted along with non-enzymatically-derived modified SVF. Bone formation was observed on and around Si-HA, reflecting osseointegration. In conclusion, Si-HA is osteoconductive and promotes osteogenesis, and its use with SVF enhances osteogenesis.


Lack of association of birth size with polymorphisms of two imprinted genes, IGF2R and GRB10.
Little is known about the determinants of birth size variability among individuals. Maternal and nutritional factors have been studied, but familial clustering suggests genetic factors as well. As a first step in testing this hypothesis, we examined common sequence variants in IGF2R and GRB10, two genes involved in the regulation of growth and subject to parental imprinting. The IGF2R gene was scanned with five polymorphisms spanning the coding and 3'-UTR for possible association with birth size in a set of 97 normal newborns in Greece. In addition, a silent SNP in GRB10 exon 2 was similarly tested as an exploratory first step. Birth weight and length were compared between groups of newborns divided according to which allele they had received from heterozygous parents. No significant differences were found between alleles in either gene, examined either by parental origin or in aggregate. Thus, we found no evidence that IGF2R variants modulate intrauterine growth within the normal range. If such variants exist in GRB10, they are not in linkage disequilibrium with the marker studied.


Heterogeneity of pumpkin ribosomal DNA.
The ribosomal DNA (rDNA) of Cucurbita pepo L. has been found to consist of tandemly arrayed repeat units, most of which are 10 kilobases in length. Thirty-six repeat units, cloned into the HindIII site of pACYC 177, fall into seven classes which differ from each other in length and/or nucleotide sequence. Most of the heterogeneity occurs in noncoding portions of the repeat unit although there is some nucleotide sequence variation in the coding portion as well. Heterogeneity of base modification was observed in genomic rDNA of which two examples are: (a) all of the repeat units have three BamHI sites, one of which is unavailable for restriction in about half of the units and (b) all of the CCGG sites except one are methylated at the internal cytidine in many of the units; a second site is unmethylated in some of the units and in a very few units a third site remains unmethylated.


Mechanisms of palmitate-induced lipotoxicity in human osteoblasts.
The interest in the relationship between fat and bone has increased steadily during recent years. Fat could have a lipotoxic effect on bone cells through the secretion of fatty acids. Palmitate is the most prevalent fatty acid secreted by adipocytes in vitro. Considering that palmitate has shown a high lipotoxic effect in other tissues, here we characterized the lipotoxic effect of palmitate on human osteoblasts (Obs). Initially we tested for changes in palmitoylation in this model. Subsequently we compared the capacity of Obs to differentiate and form bone nodules in the presence of palmitate. From a mechanistic approach, we assessed changes in nuclear activity of β-catenin and runt-related transcription factor 2 (Runx2)/phosphorylated mothers against decapentaplegic (Smad) complexes using Western blotting and confocal microscopy. Quantitative real-time PCR showed negative changes in gene expression of palmitoyltransferase genes. Furthermore, palmitate negatively affected differentiation and bone nodule formation and mineralization by Obs. Although the expression of β-catenin in palmitate-treated cells was not affected, there was a significant reduction in the transcriptional activities of both β-catenin and Runx2. Confocal microscopy showed that whereas Runx2 and Smad-4 and -5 complex formation was increased in bone morphogenetic protein-2-treated cells, palmitate had a negative effect on protein expression and colocalization of these factors. In summary, in this study we identified potential mechanisms of palmitate-induced lipotoxicity, which include changes in palmitoylation, defective mineralization, and significant alterations in the β-catenin and Runx2/Smad signaling pathways. Our evidence facilitates the understanding of the relationship between fat and bone and could allow the development of new potential therapies for osteoporosis in older persons.


Association between LMP2 and LMP7 gene polymorphisms and the risk of gastric cancer: A case-control study.
The integrality of low molecular weight protein (LMP)2/LMP7 function plays an important role in the processing of GC cell antigens. The purpose of the present hospital-based case-control study was to estimate the effect of polymorphisms in the LMP2 and LMP7 genes on the risk of GC. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to distinguish the Arg to His substitution at codon 60 of LMP2 (LMP2-60) and the Gln to Lys substitution at codon 145 of LMP7 (LMP7-145) in 502 gastric cancer patients and 502 age and gender-matched cancer-free control individuals. The Lys allele of the LMP7-145 variant was more frequent in GC patients compared with control individuals [P=0.004; adjusted odds ratio (OR), 1.39; 95% confidence interval (CI), 1.11-1.74]. The Gln/Lys and Lys/Lys genotypes increased the risk of GC compared with the Gln/Gln genotype (P=0.049 and P=0.041, respectively; adjusted OR, 1.32 and 2.13, respectively; 95% CI, 1.00-1.73 and 1.03-4.39, respectively). Compared with the Gln/Gln genotype, the LMP7-145 Gln/Lys and Lys/Lys variants of the LMP7 gene were also associated with increased susceptibility to GC (P=0.017; adjusted OR, 1.38; 95% CI, 1.06-1.80). Haplotype analysis revealed that the LMP2 (Arg)-LMP7 (Lys) haplotype was associated with increased risk of GC (P=0.013, adjusted OR=1.34, 95% CI=1.06-1.70). Stratified analysis revealed that the association between the risk of GC and the variant genotypes of LMP7-145 was stronger in older individuals (>59 years), males and non-smokers. However, no association between the LMP2-60 polymorphism and the risk of GC was observed. The present results suggest that the LMP7-145 genetic variant contributes to increased susceptibility to GC, and the Lys allele is an independent risk factor for GC.


Biochemical and histopathological evidences for beneficial effects of satureja khuzestanica jamzad essential oil on the mouse model of inflammatory bowel diseases.
The essential oil from Satureja Khuzestanica Jamzad (SKEO), an endemic plant from Iran, was evaluated for its activity against inflammatory bowel disease (IBD). SKEO was examined on the experimental mouse model of inflammatory bowel disease, which is acetic acid-induced colitis. Prednisolone was used as the standard drug for comparison. Biochemical, macroscopic, and microscopic examinations of colon were performed. Lipid peroxidation significantly increased in acetic acid-treated mice in comparison to the normal group (4.88 vs. 3.02 mumol/g) and was significantly restored by SKEO (500, 1000, 1500 ppm) and prednisolone treatment. The mean percentage of decreases of lipid peroxidation in SKEO (500, 1000, 1500 ppm)- and prednisolone-treated groups were 10.5, 28.5, 42.85, and 33.33 of control, respectively. The myeloperoxidase activity significantly increased in acetic acid-treated mice in comparison to the normal group (4.1 vs. 0.8 U/g) and significantly restored in SKEO (1000 and 1500 ppm)- and prednisolone-treated groups. The mean percentage of decreases of myeloperoxidase activity in SKEO (1000 and 1500 ppm)- and prednisolone-treated groups were 24.56, 50, and 52.63 of control, respectively. SKEO (1000 and 1500 ppm)- and prednisolone-treated groups showed significantly lower score values of macroscopic and microscopic characters when compared to the acetic acid-treated group. The beneficial effect of SKEO (1500 ppm) was comparable to that of prednisolone. Known antioxidant, antimicrobial, antiinflammatory, and antispasmodic potentials of Satureja Khuzestanica may be the mechanisms by which this plant protects animals against experimentally induced IBD. Proper clinical investigation should be carried out to confirm the activity in human disease.


Walking energy harvesting and self-powered tracking system based on triboelectric nanogenerators.
Due to the extensive energy consumption and high population density in modern cities, the collection and use of scattered walking energy from the stream of people is crucial for the development of a green ecological city. Herein, a flexible undulated electrode-based triboelectric nanogenerator (u-TENG) was integrated to the floor to scavenge walking energy from pedestrians, promoting the ordered collection of disordered and scattered energy. Driven by the steps of human walking, the output of the as-fabricated u-TENG are an open-circuit voltage of 86 V and a short-circuit current of 6.2 μA, which are able to continuously light up 110 light-emitting diode bulbs. In addition, a self-powered location-tracking system was prepared for pedestrian volume counting and passenger tracing with the purpose of reducing energy consumption in public areas. The proposed walking energy harvesting device is flexible, feasible, and unaffected by season, climate, or location. This work not only proposes a strategy for mechanical energy harvesting in public areas, including subway stations, hospitals, shopping malls, and business streets, but also offers a novel solution for smart cities and low-carbon transportation alternatives.


Aggregation-Driven Controllable Plasmonic Transition of Silica-Coated Gold Nanoparticles with Temperature-Dependent Polymer-Nanoparticle Interactions for Potential Applications in Optoelectronic Devices.
Localized surface plasmon resonance (LSPR) effect relies on the shape, size, and dispersion state of metal nanoparticles and can potentially be employed in many applications such as chemical/biological sensor, optoelectronics, and photocatalyst. While complicated synthetic approaches changing shape and size of nanoparticles can control the intrinsic LSPR effect, here we show that controlling interparticle interactions with silica-coated gold nanoparticles (Au@SiO2 NPs) is a powerful approach, permitting wide range of optical bandwidth of gold nanoparticles with great stability. The interparticle interactions of Au@SiO2 NPs are controlled through concentration-, temperature-, and time-dependent polymer-induced interactions. The polymer-induced interactions modulate the state of particle dispersion, resulting an effective plasmonic shift by more than 200 nm. We further explore the microstructure of particle aggregation and explain mechanisms of plasmonic shift based on the results of small-angle X-ray scattering (SAXS) and discrete dipole approximation (DDA) calculation. We show that an effective control of LSPR behavior is now available through trapped aggregation of Au@SiO2 NPs with temperature variation. We anticipate that the suggested strategy can be employed in many practical applications such as optical bioimaging and optoelectronic devices.


[Rearrangement and expression of bcr-abl genes in CML and ALL].
We have carried out the molecular and cell-biological analysis on Ph1-positive leukemias in this study. Five out of nine Ph1-positive ALL cases showed molecular rearrangement within the classical bcr sequence (or M-bcr), similar as those in 47 CML cases. We examined 4 cases of Ph1-positive ALL presenting no rearrangement of M-bcr and found that, in 2 of 4 cases, one showed the breakpoint in a 5 kb segment of the bcr gene first intron (bcr-2) and the other in bcr-1, 16 kb upstream of bcr-2. Ph1-positive ALL frequently showed biphenotypical or biclonal phenotypes of myeloid and lymphoid lineages. Furthermore, we demonstrated the ability of two Ph1-positive ALL cell lines to differentiate into monocytic lineage in vitro, thus suggesting the possibility that these Ph1-positive ALL cells might reside on the stage of multipotent stem cell along the hematopoietic cell differentiation. Two out of 31 CML cases showed the mutations of the ras genes by the polymerase chain reaction; one case in the crisis phase and the other in the chronic phase. However, no mutations of the fms genes was detected. Two cases in the crisis phase of 24 CML patients (11 cases in the chronic phase and 13 cases in the crisis phase) contained rearrangements of the p53 gene by Southern analysis. Furthermore, the transcriptional alteration was found in 2 CML-BC and 2 CML-BC derived cell lines' samples, suggesting a important role of the p53 gene in the transformation of CML into the crisis phase.


[Clinical and radiological features of inflammatory lesions in the lower molars area].
The study objective was to analyze clinical manifestations by various forms of inflammatory destructive lesions in lower molars area. The study included 54 patients aged 20 to 66 years with odontogenic alveolar bone defects in lower molars area. Typical clinical and radiological signs are described for each type of destructive lesions. Sinus tract located more coronal and 'areolar' bone resorption may indicate root perforation. Clinical and radiological features may help in choosing optimal surgical tactic.


Postoperative stiffness after reverse total shoulder arthroplasty.
The purpose of this study was to evaluate the rate and risk factors for stiffness after reverse shoulder arthroplasty and the ramifications on the patient-reported outcomes. A consecutive series of patients who underwent reverse shoulder arthroplasty were prospectively followed for one year. Passive range of motion was measured preoperatively and at regular intervals postoperatively. Patients with passive forward elevation of less than 100° or passive external rotation of less than 30° were defined as stiff. Radiographic parameters and postoperative patient-reported outcome scores were collected. Seventy-six patients were available for review. The prevalence of postoperative stiffness following reverse shoulder arthroplasty was 47% at three months, 31% at six months, and 25% at one year. Preoperative shoulder stiffness was associated with three-month postoperative stiffness only. In patients with one-year stiffness, smaller (p = 0.03) and less lateralized glenospheres (p = 0.024) were more common. Stiffness was not associated with one-year patient-reported outcome scores. Stiffness is common after reverse shoulder arthroplasty and often improves at one-year after surgery. Implant design and selection may be important determinants of passive range of motion. While stiffness does not appear to influence patient-reported outcome scores, one of four patients will potentially have stiffness one year following reverse shoulder arthroplasty.Level of evidence: Level III; retrospective study.


[Scrotal reconstruction after necrotizing cellulitis of the perineum and external genital organs. Apropos of 21 cases].
The author report twenty one cases of tissue reconstruction defects secondary to necrotizing cellulitis of perineum and external genital organs, treated at the burns and plastic surgery unit of CHU Ibn Rochd of Casablanca, between 1992 and 1994. Depending on the extent of the defect, the techniques used were gracilis musculocutaneous flap in 8 cases, thigh fasciocutaneous flap in 7 cases, groin flap in 4 cases, simple skin sutures and skin grafts in one case, respectively. The morphological results were satisfactory. The mean hospital stay after reconstruction was 15 days.


Complications of anterior subcutaneous internal fixation for unstable pelvis fractures: a multicenter study.
Stabilization after a pelvic fracture can be accomplished with an anterior external fixator. These devices are uncomfortable for patients and are at risk for infection and loosening, especially in obese patients. As an alternative, we recently developed an anterior subcutaneous pelvic internal fixation technique (ASPIF). We asked if the ASPIF (1) allows for definitive anterior pelvic stabilization of unstable pelvic injuries; (2) is well tolerated by patients for mobility and comfort; and (3) has an acceptable complication rate. We retrospectively reviewed 91 patients who incurred an unstable pelvic injury treated with an anterior internal fixator and posterior fixation at four Level I trauma centers. We assessed (1) healing by callous formation on radiographs and the ability to weightbear comfortably; (2) patient function by their ability to sit, stand, lie on their sides, and how well they tolerated the implants; and (3) complications during the observation period. The minimum followup was 6 months (mean, 15 months; range, 6-40 months). All 91 patients were able to sit, stand, and lie on their sides. Injuries healed without loss of reduction in 89 of 91 patients. Complications included six early revisions resulting from technical error and three infections. Irritation of the lateral femoral cutaneous nerve was reported in 27 of 91 patients and resolved in all but one. Heterotopic ossification around the implants, which was asymptomatic in all cases, occurred in 32 of 91 patients. The anterior internal fixator provided high rates of union for the anterior injury in unstable pelvic fractures. Patients were able to sit, stand and ambulate without difficulty. Infections and aseptic loosening were reduced but heterotopic ossification and irritation of the LFCN are common. Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.


Immunoexpression of Cyclin D1 and PTEN in Various Endometrial Pathologies.
To determine the expression of cyclin D1 and PTEN (phosphatase and tensin homolog) in endometrial hyperplasias and neoplasias. Analytical study. The study was conducted at BMSI, JPMC, Karachi, from January 2008 to December 2012. Analysis of endometrial samples, comprising of hysterectomies and curettage, was carried out. Immunohistochemical staining was done for PTEN and cyclin D1 expression. Fifty-three endometrial samples including 23 endometrial carcinomas, 6 complex hyperplasias with atypia, 14 complex hyperplasias without atypia, 6 simple hyperplasias without atypia and 4 normal proliferative endometrium were analyzed. Fifty-two percent (12 out of 23) and 48% (11 out of 23) cases of endometrial carcinomas showed complete loss of PTEN expression and cyclin D1 over expression, respectively. Five (5 out of 6) cases of complex hyperplasias with atypia and 64.28% (9 out of 14) cases of complex hyperplasia without atypia showed complete loss of or diminished expression of PTEN whereas 66.66% (4 out of 6) cases of endometrial hyperplasia with atypia and 50% (7 out of 14) cases of endometrial hyperplasia without atypia showed cyclin D1 overexpression (p < 0.001). Loss of PTEN, expression and cyclin D1 overexpression was seen in a significant number of well differentiated endometrial adenocarcinomas and complex hyperplasias with atypia, suggesting both as an early event in endometrial carcinogenesis.


Identification of novel transcriptional networks in response to treatment with the anticarcinogen 3H-1,2-dithiole-3-thione.
3H-1,2-dithiole-3-thione (D3T), an inducer of antioxidant and phase 2 genes, is known to enhance the detoxification of environmental carcinogens, prevent neoplasia, and elicit other protective effects. However, a comprehensive view of the regulatory pathways induced by this compound has not yet been elaborated. Fischer F344 rats were gavaged daily for 5 days with vehicle or D3T (0.3 mmol/kg). The global changes of gene expression in liver were measured with Affymetrix RG-U34A chips. With the use of functional class scoring, a semi-supervised method exploring both the expression pattern and the functional annotation of the genes, the Gene Ontology classes were ranked according to the significance of the impact of D3T treatment. Two unexpected functional classes were identified for the D3T treatment, cytosolic ribosome constituents with 90% of those genes increased, and cholesterol biosynthesis with 91% of the genes repressed. In another novel approach, the differentially expressed genes were evaluated by the Ingenuity computational pathway analysis tool to identify specific regulatory networks and canonical pathways responsive to D3T treatment. In addition to the known glutathione metabolism pathway (P = 0.0011), several other significant pathways were also revealed, including antigen presentation (P = 0.000476), androgen/estrogen biosynthesis (P = 0.000551), fatty acid (P = 0.000216), and tryptophan metabolism (P = 0.000331) pathways. These findings showed a profound impact of D3T on lipid metabolism and anti-inflammatory/immune-suppressive response, indicating a broader cytoprotective effect of this compound than previously expected.


Critical care ultrasonography during COVID-19 pandemic: The ORACLE protocol.
Coronavirus disease 2019 (COVID-19) is characterized by severe lung involvement and hemodynamic alterations. Critical care ultrasonography is vital because it provides real time information for diagnosis and treatment. Suggested protocols for image acquisition and measurements have not yet been evaluated. This cross-sectional study was conducted at two centers from 1 April 2020 to 30 May 2020 in adult patients with confirmed COVID-19 infection admitted to the critical care unit. Cardiac and pulmonary evaluations were performed using the ORACLE protocol, specifically designed for this study, to ensure a structured process of image acquisition and limit staff exposure to the infection. Eighty-two consecutively admitted patients were evaluated. Most of the patients were males, with a median age of 56 years, and the most frequent comorbidities were hypertension and type 2 diabetes, and 25% of the patients had severe acute respiratory distress syndrome. The most frequent ultrasonographic findings were elevated pulmonary artery systolic pressure (69.5%), E/e' ratio > 14 (29.3%), and right ventricular dilatation (28%) and dysfunction (26.8%). A high rate of fluid responsiveness (82.9%) was observed. The median score (19 points) on pulmonary ultrasound did not reveal any variation between the groups. Elevated pulmonary artery systolic pressure was associated with higher in-hospital mortality. The ORACLE protocol was a feasible, rapid, and safe bedside tool for hemodynamic and respiratory evaluation of patients with COVID-19. Further studies should be performed on the alteration in pulmonary hemodynamics and right ventricular function and its relationship with outcomes.


[Vitreous surgery for macular edema in branch retinal vein occlusion].
To examine the efficacy of vitreous surgery for macular edema in branch retinal vein occlusion (BRVO). This study included 183 patients (183 eyes) that underwent vitreous surgery for macular edema in BRVO. They were 77 males and 106 females. The average age of the patients was 65 years (range, 35-87 years). The average duration of macular edema was 18 weeks (range, 1-161 weeks). Mean preoperative visual acuity was 0.32 (0.01-1.2). Preoperative visual acuity was less than 0.1 in 27% and more than 0.5 in 26% of the cases. The average follow-up period was 24 months (range, 12-83 months). Macular edema was absorbed in 21% at 1 month, 54% at 3 months, 81% at 6 months, and 95% at 12 months postoperatively. The mean absorption period of macular edema was 4.5 months. Postoperative visual acuity improved to 0.68, which was statistically significant. Postoperative visual acuity was less than 0.1 in 9% of the cases, more than 0.5 in 68%, and more than 0.8 in 47%. After vitreous surgery for macular edema in BRVO, macular edema was absorbed rapidly and visual acuity improved. Vitreous surgery may be an effective treatment.


[Sudden unexpected cardiac death in an 18-year-old female with familial hypercholesterolaemia].
Familial hypercholesterolaemia (FH) is a well-defined but underdiagnosed dyslipidaemia occurring in 1:500 persons. We report a case where an 18-year-old woman with an untreated FH dies a sudden cardiac death due to acute myocardial infarction. In patients with FH atherosclerotic manifestations are common at a young age and FH should always be suspected in patients with P-low-density lipoprotein cholesterol level above 5 mmol/l (4 mmol/l for persons < 16 years of age). Patients with FH should be referred to specialized units so that family members with FH systematically are identified.


A systematic review and meta analysis of the longevity of anterior and posterior all-ceramic crowns.
Clinical experience suggests that there is a difference in survival between anterior and posterior all ceramic restorations. This systematic review compared the difference in survival for full coverage all-ceramic materials used in adults to restore anterior or posterior vital teeth, not involved with fixed dental prostheses, but opposed by teeth. Searches using Medline, Embase, and the Cochrane Library, including hand searches, with the inclusion criteria containing all-ceramic full coverage crowns in human adults over 17 years of age, prospective and retrospective studies, opposed by teeth, periodontal pocketing ≤5mm, but not involving implant supported crowns or non-vital teeth. All papers were published between 1980 and March 2014 and available in English. From the selected studies a meta analysis was undertaken. The chi square test, I2, Begg's and Egger's test were analysed and the publication bias was assessed using a Funnel plot. The, Kappa scores were 0.63, 0.88, and 0.81 at each selection stage. Pooled data produced 1112 anterior crowns with 73 failures (6.5%) and 1821 posterior crowns with 166 failures (9.1%) with a follow up time from 36 to 223 months. Relative risk meta-analysis of the 14 selected papers demonstrated that anterior all-ceramic crowns were 50% less likely to fail than posterior all-ceramic crowns (p=0.001). These results indicate that there were differences in failure between anterior and posterior all ceramic crowns but the difference was only 3%. Although this has clinical relevance and some caution is needed when prescribing all ceramic posterior crowns the difference was relatively small. The clinically relevant results of this review, based on currently available data, demonstrate a need for some caution when considering posterior all-ceramic crowns. Lithium disilicate restorations were observed to have higher failures on anterior restorations and more research is needed to investigate why.


Interaction between passive smoking and two HLA genes with regard to multiple sclerosis risk.
The recently described interaction between smoking, human leukocyte antigen (HLA) DRB1*15 and absence of HLA-A*02 with regard to multiple sclerosis (MS) risk shows that the risk conveyed by smoking differs depending on genetic background. We aimed to investigate whether a similar interaction exists between passive smoking and HLA genotype. We used one case-control study with incident cases of MS (736 cases, 1195 controls) and one with prevalent cases (575 cases, 373 controls). Never-smokers with different genotypes and passive smoking status were compared with regard to occurrence of MS, by calculating odds ratios (ORs) with 95% confidence intervals (CIs). The potential interaction between different genotypes and passive smoking was evaluated by calculating the attributable proportion (AP) due to interaction. An interaction was observed between passive smoking and carriage of HLA-DRB1*15 (AP 0.3, 95% CI 0.02-0.5 in the incident study, and AP 0.4, 95% CI 0.1-0.7 in the prevalent study), as well as between passive smoking and absence of HLA-A*02. Compared with non-smokers without any of these two genetic risk factors, non-exposed subjects with the two risk genotypes displayed an OR of 4.5 (95% CI 3.3-6.1) whereas the same genotype for subjects exposed to passive smoking rendered an OR of 7.7 (95% CI 5.5-10.8). The risk of developing MS associated with different HLA genotypes may be influenced by exposure to passive smoking. The finding supports our hypothesis that priming of the immune response in the lungs may subsequently lead to MS in people with a genetic susceptibility to the disease.


Measurement of Calcineurin Phosphatase Activity in Cell Extracts
The calmodulin-dependent phosphatase calcineurin is an important molecular target of the immunosuppressive drugs cyclosporin A (CsA) and FK506. Complexes of CsA and FK506 with their immunophilin ligands interact with calcineurin in vitro, resulting in the inhibition of its serine/threonine phosphatase activity toward polypeptide substrates. In order to demonstrate that CsA and FK506 inhibit calcineurin in vivo, we developed an assay to measure calcineurin phosphatase activity in crude cell extracts. We have previously reported that incubation of intact cells with nanomolar concentrations of either CsA or FK506 results in potent inhibition of calcineurin activity in a variety of cell lines. Here we discuss in detail the methodology and applications of the cell extract calcineurin assay.


Chicken anaemia agent: a review.
Chicken anaemia agent (CAA) is a small, unclassified, icosahedral DNA virus with a single-stranded, circular genome. It seems to have a worldwide distribution. Only one serotype of CAA has been found, and all isolates investigated so far are pathogenic for young chicks. CAA causes a syndrome in chickens characterised by increased mortality, anaemia associated with atrophy of the haematopoietic tissues in the bone marrow, subcutaneous and intramuscular haemorrhages, and atrophy of the lymphoid system. CAA spreads both vertically and horizontally. Vertical transmission occurs following primary infection of in-lay breeding stock, and results in clinical disease in their progeny around 2 weeks of age. Horizontal spread usually results in subclinical disease. Both clinical and subclinical disease cause economic loss. Current control measures often involve controlled exposure of breeding flocks to CAA during the rearing period. A vaccine is indicated.


Chlorhexidine gluconate mouthwashes as a surfactant for addition-reaction silicone impressions.
Addition-reaction silicone impression (PVS) materials are hydrophobic. Hydrophobicity of the impression material may interfere with the wetting of the tooth, resulting in void formation. The study investigates whether conditioning teeth with Chlorhexidine-gluconate based mouthwashes can reduce the hydrophobicity and the number of voids on PVS impressions. Impression material contact angle specimens on bovine tooth surfaces were measured using a Reflex Microscope. PVS impressions (President) were made of untreated bovine teeth in three groups (1, 2 and 3) and fourth group used Impregum polyether impression material: Group I was used as a control group, and original and mint flavoured Corsodyl (Chlorhexidine) mouthwashes were used as clinical surfactants in Groups 2 and 3, respectively. Contact angle readings were recorded on each side of every impression in each of the four groups and compared by an analysis of variance. In the second part of the study, the numbers of air voids on impression surfaces were visually recorded. The proportions of air voids in the groups were compared using a Chi-squared test. The mean angle for Group 3 with mint flavoured Corsodyl mouthwash was significantly smaller than that of any of the other groups (P < 0.05). The only statistically significant (P < 0.01) comparisons of the proportions of air voids were between Group 4 and each of the other experimental groups, with the percentage of voids being significantly greater in Group 4. Although Corsodyl mint significantly reduced the mean contact angle it did not significantly reduce the percentage of voids on impression surfaces.


Determination of the Chemical-Shift Difference between the Lactate Multiplets and Its pH Dependence
A volume-selective NMR method is presented for very exact determination of the difference of the Larmor frequencies between the coupled resonances of homonuclear AX3 spin systems, as, for example, lactate. The frequency difference can be determined with an accuracy of 0.003 ppm even if only the doublet of the spin system can be detected. The method is based on the effects of homonuclear polarization transfer which occurs in localized double-spin-echo spectroscopy. It is used for determination of the chemical-shift difference of the lactate multiplets, which depends on the degree of dissociation and consequently on pH. Measurements were performed with a 1.5 T Siemens Magnetom SP 63 whole-body imager on solutions of lactate and acetic acid in physiological sodium chloride solution with pH from 1 to 11. As a consequence of these measurements, conclusions are possible for the optimum echo time for PRESS measurements which avoid signal losses from polarization transfer. Furthermore, the possibility of localized pH determination by this effect is discussed.


Lymphocytes accelerate epithelial tight junction assembly: role of AMP-activated protein kinase (AMPK).
The tight junctions (TJs), characteristically located at the apicolateral borders of adjacent epithelial cells, are required for the proper formation of epithelial cell polarity as well as for sustaining the mucosal barrier to the external environment. The observation that lymphocytes are recruited by epithelial cells to the sites of infection [1] suggests that they may play a role in the modulation of epithelial barrier function and thus contribute to host defense. To test the ability of lymphocytes to modulate tight junction assembly in epithelial cells, we set up a lymphocyte-epithelial cell co-culture system, in which Madin-Darby canine kidney (MDCK) cells, a well-established model cell line for studying epithelial TJ assembly [2], were co-cultured with mouse lymphocytes to mimic an infection state. In a typical calcium switch experiment, the TJ assembly in co-culture was found to be accelerated compared to that in MDCK cells alone. This accelaration was found to be mediated by AMP-activated protein kinase (AMPK). AMPK activation was independent of changes in cellular ATP levels but it was found to be activated by the pro-inflammatory cytokine TNF-alpha. Forced suppression of AMPK, either with a chemical inhibitor or by knockdown, abrogated the accelerating effect of lymphocytes on TJ formation. Similar results were also observed in a co-culture with lymphocytes and Calu-3 human airway epithelial cells, suggesting that the activation of AMPK may be a general mechanism underlying lymphocyte-accelerated TJ assembly in different epithelia. These results suggest that signals from lymphocytes, such as cytokines, facilitate TJ assembly in epithelial cells via the activation of AMPK.


A Mathematical Treatment of Munch's Pressure-Flow Hypothesis of Phloem Translocation.
The steady state solutions of two mathematical models are used to evaluate Münch's pressure-flow hypothesis of phloem translocation. The models assume a continuous active loading and unloading of translocate but differ in the site of loading and unloading and the route of water to the sieve tube. The dimensions of the translocation system taken are the average observed values for sugar beet and are intended to simulate translocation from a mature source leaf to an expanding sink leaf. The volume flow rate of solution along the sieve tube, water flow rate into the sieve tube, hydrostatic pressure, and concentration of sucrose in the sieve tube are obtained from a numerical computer solution of the models. The mass transfer rate, velocity of translocation, and osmotic and hydrostatic pressures are consistent with empirical findings. Owing to the resistance to water flow offered by the lateral membranes, the hydrostatic pressure generated by the osmotic pressure can be considerably less than would be predicted by the solute concentration. These models suggest that translocation at observed rates and velocities can be driven by a water potential difference between the sieve tube and surrounding tissue and are consistent with the pressure-flow hypothesis of translocation.


Association between lung cancer somatic mutations and occupational exposure in never-smokers.
Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure.BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations.Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency.Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.


Full Monte Carlo-Based Biologic Treatment Plan Optimization System for Intensity Modulated Carbon Ion Therapy on Graphics Processing Unit.
One of the major benefits of carbon ion therapy is enhanced biological effectiveness at the Bragg peak region. For intensity modulated carbon ion therapy (IMCT), it is desirable to use Monte Carlo (MC) methods to compute the properties of each pencil beam spot for treatment planning, because of their accuracy in modeling physics processes and estimating biological effects. We previously developed goCMC, a graphics processing unit (GPU)-oriented MC engine for carbon ion therapy. The purpose of the present study was to build a biological treatment plan optimization system using goCMC. The repair-misrepair-fixation model was implemented to compute the spatial distribution of linear-quadratic model parameters for each spot. A treatment plan optimization module was developed to minimize the difference between the prescribed and actual biological effect. We used a gradient-based algorithm to solve the optimization problem. The system was embedded in the Varian Eclipse treatment planning system under a client-server architecture to achieve a user-friendly planning environment. We tested the system with a 1-dimensional homogeneous water case and 3 3-dimensional patient cases. Our system generated treatment plans with biological spread-out Bragg peaks covering the targeted regions and sparing critical structures. Using 4 NVidia GTX 1080 GPUs, the total computation time, including spot simulation, optimization, and final dose calculation, was 0.6 hour for the prostate case (8282 spots), 0.2 hour for the pancreas case (3795 spots), and 0.3 hour for the brain case (6724 spots). The computation time was dominated by MC spot simulation. We built a biological treatment plan optimization system for IMCT that performs simulations using a fast MC engine, goCMC. To the best of our knowledge, this is the first time that full MC-based IMCT inverse planning has been achieved in a clinically viable time frame.


USP7: Target Validation and Drug Discovery for Cancer Therapy.
USP7 (ubiquitin specific protease 7, also known as HAUSP) is one of the deubiquitinating enzymes (DUB) that reverses ubiquitination and spares substrate proteins from degradation. After a brief introduction of ubiquitin-proteasome system (UPS) and human DUB, this review focuses on the structural and functional complexity of USP7 in tumor development and progression. Afterwards, physiological regulatory mechanisms and manipulation strategies for USP7 are elaborated. Finally, we discuss the advances and difficulties of USP7 as a novel therapeutic target for cancer. It is mostly concerned that USP7 regulates the dynamics of the p53 and Mdm2 network by deubiquitinating both p53 and its E3 ubiquitin ligase, Mdm2. Recently, USP7 has also been recognized as a regulator of many other tumor associated proteins such as FOXO, PTEN and Claspin, consequently being involved in cell cycle control, DNA damage response, apoptosis and many other cellular processes. Consistently, aberrant USP7 expression and activity have been connected to various types of cancers, which along with lots of validating genetic and functional experiments make this enzyme a compelling target for the treatment of cancer. Currently disclosed inhibitor discovery programs and relevant research have identified several synthetic small molecules, natural compounds, small peptides and one ubiquitin variant that have specific USP7 inhibitory effects and considerable antitumor activities. Taken together, USP7 is a promising therapeutic target and USP7 inhibitors hold promise as a new approach to cancer therapy.


Microarray analysis of long non-coding RNA and mRNA expression profiles in diabetic cardiomyopathy using human induced pluripotent stem cell-derived cardiomyocytes.
This study aims to investigate the altered expression signature of long non-coding RNAs, mRNAs and deregulated pathways related to diabetic cardiomyopathy disease pathogenesis. We utilize the previously established in vitro diabetic cardiomyopathy model of human induced pluripotent stem cell-derived human cardiomyocytes to perform long non-coding RNA and mRNA expression analysis on glucose (11 mM), endothelin-1 (10 nM) and cortisol (1 µM) stimulated human induced pluripotent stem cell-derived human cardiomyocytes to interrogate diabetic cardiomyopathy associated RNA expression profile. Out of 20,730 mRNAs and 40,173 long non-coding RNAs being screened, 2046 long non-coding RNAs and 1582 mRNAs were differentially regulated (fold change > 2, p < 0.05) between diabetic cardiomyopathy and control group, of which more than half were intergenic and antisense long non-coding RNAs. Most of the coding transcripts were associated with processes like inflammation, structural reorganization, metabolism, smooth muscle contraction, focal adhesion and repair contributing towards the development of diabetic cardiomyopathy. The subgroup analysis further revealed 411 long non-coding RNAs being co-expressed with neighbouring genes. However, our coding-non-coding co-expression analysis showed an overall 48,155 co-expression network connections. In addition to that, the long non-coding RNAs with highest network connections were profoundly enriched for focal adhesion, cell-matrix adhesion and muscle contraction. These results provide comprehensive data about the pathways and regulatory mechanisms associated with diabetic cardiomyopathy and indicate that long non-coding RNAs may play a crucial role in diabetic cardiomyopathy.


HMGB1 enhances mechanical stress-induced cardiomyocyte hypertrophy in vitro via the RAGE/ERK1/2 signaling pathway.
Pressure overload‑induced cardiac hypertrophy is associated with a complex spectrum of pathophysiological mechanisms, including the inflammation response. High mobility group box‑1 (HMGB1), a pro‑inflammatory cytokine, is not only increased in myocardium under pressure overload, but also exacerbates pressure overload‑induced cardiac hypertrophy and dysfunction; however, the underlying mechanisms have remained elusive. In the present study, cultured cardiomyocytes were stimulated by mechanical stress and/or HMGB1 for various durations to examine the role of HMGB1 in cardiomyocyte hypertrophy, and to detect the expression of receptor for advanced glycation end products (RAGE), toll‑like receptor 4 (TLR‑4) and the activation status of mitogen‑activated protein kinases (MAPKs) and Janus kinase 2 (JAK2)/STAT3. The results indicated that HMGB1 aggravated mechanical stress‑induced cardiomyocyte hypertrophy. Furthermore, mechanical stress and HMGB1 stimulation activated extracellular signal‑regulated kinase 1/2 (ERK1/2), P38 and JAK2/STAT3 signaling in cardiomyocytes, but an additive effect of the combined stimuli was only observed on the activation of ERK1/2. In addition, mechanical stress caused a prompt upregulation of the expression of RAGE and TLR‑4 in cardiomyocytes, while the activation of ERK1/2 by HMGB1 was inhibited by blockage of RAGE, but not by blockage of TLR‑4. In summary, the present results indicated that extracellular HMGB1 enhanced mechanical stress‑induced cardiomyocyte hypertrophy in vitro, at least partially via the RAGE/ERK1/2 signaling pathway.


Evaluation of recellularization on decellularized aorta scaffolds engineered by ultrasonication treatment.
Aortic scaffolds prepared using sonication decellularization treatment has provided a successful medium for repopulation with vascular smooth muscle cells (VSMCs). The objective of this study is to explore the potential of tissue decellularization using ultrasonication treatment and its recellularization before implantation of the cell-seeded scaffolds into host. Aorta tissue samples are decellularized in 2% SDS with sonication for 10 hours and compared with the native tissues. The 4',6-diamidino-2-phenylindole (DAPI) staining was used to evaluate the decellularization and Hematoxylin-Eosin (H-E) staining was used to compare the VSMCs infiltrations onto the decellularized tissues at day-0 and day-6 after cell-seeding. The results histologically showed complete DNA removal from scaffolds after decellularization and subsequent recellularization resulted in successful VSMCs infiltration. Accordingly, the decellularized tissues treated with 2% SDS in sonication demonstrated successful VSMCs repopulation afterward and is speculated to have less toxicity and able to be effectively implanted into host.


[Hemodialysis with electrochemical regeneration of dialysis solution].
The method of electrochemical regeneration of dialysis solution is virtually as effective as the traditional hemoperfusion system in removing creatinine and potassium ions from the body, but inferior to it as regards urea and inorganic phosphorus and superior in removal of medium-weight toxins. A more smooth reduction of urea level in the blood provides relatively stable hemodynamics in patients liable to hypotension. Electrochemical regeneration permits a continuous purification of dialysis solution, the regeneration block may be used many times, and sodium hypochlorite produced during electrolysis operation maintains the sterility of the system. Electrochemical regeneration does not require water purification systems, water communication, and dialysis concentrate, this permitting the performance of detoxication in rooms without special equipment.


Tooth loss and chewing capacity among older adults in Adelaide.
This study aimed to identify sociodemographic factors associated with edentulism (loss of all teeth) and the average number of teeth lost, and to investigate relationships between tooth loss and chewing capacity. Data were obtained in 1991-92 from a cross-sectional oral epidemiological survey of Adelaide residents aged 60+ years. Interviews with 1160 participants provided information on edentulism while oral examinations among 560 dentate participants and 313 edentulous participants provided information on the number of missing teeth. People were asked if they could chew or bite six common foods. Some 41.1 per cent of persons were edentulous, and nearly half the natural teeth (mean 15.2) were missing among dentate people. Multivariate analyses revealed higher rates of edentulism (P < or = 0.05) for people who were older, female, Australian-born, or holders of pensioner health benefit cards, and for people who left school at an early age, or who did not own their residence. Among dentate people there were more (P < or = 0.05) missing teeth among those who were older, Australian-born, health benefit card holders, and who left school at an early age. Some 37.9 per cent of people reported difficulty chewing at least one food, although 57 per cent of dentate people and virtually all edentulous people wore dentures. Difficulty chewing was associated with tooth loss: 6.1 per cent of people with fewer than nine missing teeth reported difficulty compared with S8.6 per cent of edentulous people (P < 0.01). The findings show substantially compromised oral health among older adults, particularly the oldest-old and disadvantaged groups.


[Late cryptococcal meningitis after liver transplantation].
We report a case of cryptococcal meningitis, eight years after liver transplantation for primary biliary cirrhosis. Detection of the cryptococcal antigen in serum and cerebrospinal fluid appears to be essential for initial diagnosis and follow-up. Oral fluconazole treatment alone can be effective, when given for a very long period to prevent relapse.


Parental alcohol and other drug (AOD) use and health beliefs about parent involvement in AOD prevention.
Because the family plays an important role in predicting alcohol and other drug (AOD) use among youth, prevention efforts must begin in early childhood and involve parents. The purpose of this study was to determine differences between parent AOD users and nonusers in relation to health beliefs about parent involvement in AOD prevention with preschool children. A convenience sample of 200 Head Start parents in East Central Indiana completed self-report instruments measuring Health Belief Model constructs. Almost half (45%) reported alcohol use, over half (54%) smoked cigarettes, and 11% admitted using illicit drugs. Compared to nonusers, illicit drug users were more likely to perceive their children as susceptible to future AOD use, but less likely to view AOD use by their children as serious. Compared with nonsmokers, tobacco users were more likely to perceive their children as susceptible to future AOD use and had less interest in maintaining health through early prevention activities.


High-grade glioma therapy: adding flexibility in trial design to improve patient outcomes.
Outcomes for patients with high grade gliomas have changed little over the past thirty years. This realization prompted renewed efforts to increase flexibility in the design and conduct of clinical brain tumor trials. This manuscript reviews the development of clinical trial methods, challenges and considerations of flexible clinical trial designs, approaches to improve identification and testing of active agents for high grade gliomas, and evaluation of their delivery to the central nervous system. Flexibility can be introduced in clinical trials in several ways. Flexible designs tout smaller sample sizes, adaptive modifications, fewer control arms, and inclusion of multiple arms in one study. Unfortunately, modifications in study designs cannot address two challenges that are largely responsible for the lack of progress in treating high grade gliomas: 1) the identification of active pharmaceutical agents and 2) the delivery of these agents to brain tumor tissue in therapeutic concentrations. To improve the outcomes of patients with high grade gliomas efforts must be focused on the pre-clinical screening of drugs for activity, the ability of these agents to achieve therapeutic concentrations in non-enhancing tumors, and a willingness to introduce novel compounds in minimally pre-treated patient populations.


Effect of interrupted endogenous BMP/Smad signaling on growth and steroidogenesis of porcine granulosa cells.
Bone morphogenetic proteins (BMPs) play a critical role in the growth and steroidogenesis of granulosa cells (GCs). BMP signals act through membrane-bound heteromeric serine/threonine kinase receptors. Upon ligand binding, BMPs activate intracellular Smad proteins and regulate growth and apoptosis in various cell types. The objective of this study was to demonstrate the effects of BMP/Smad signal on growth and steroidogenesis of porcine GCs. A strategy of RNA interference (RNAi)-mediated 'gene silencing' of Smad4, a core molecule mediating the intracellular BMP/Smad signal transduction pathways, was used to interrupt endogenous BMP/Smad signaling. Results indicate that Smad4-small interfering RNA (siRNA) caused specific inhibition of Smad4 mRNA and protein expression after transfection. Interrupted endogenous BMP/Smad signaling significantly inhibited growth, and induced apoptosis of porcine GCs, while decreasing estradiol production. In addition, interrupted BMP/Smad signaling significantly (P<0.05) changed the expression of Cyclin D2, CDK4, Bcl-2, and Cyp19a1. These findings provide new insights into how BMP/Smad signaling regulates the growth and steroidogenesis of porcine GCs.


Comparative evaluation of commercially available aflatoxin test methods.
Five qualitative methods and 1 quantitative aflatoxin analytical method were compared with the Holaday-Velasco (HV) minicolumn and thin-layer chromatography (TLC) methods for corn in an evaluation involving 4 U.S. Department of Agriculture Federal Grain Inspection Service (USDA-FGIS) laboratories, 1 laboratory at the University of Georgia, and 1 laboratory at the University of Arizona. Samples analyzed included 1 set of artificially contaminated corn containing both aflatoxin B1 and B2 (ratio of B1:B2 of 92:8), 1 set of artificially contaminated corn containing only aflatoxin B1, and 1 set of naturally contaminated corn. Levels of total aflatoxin tested were 0, 10, 15, 20, 25, 30, and 40 ppb. Results of analysis of these samples with each method evaluated are reported. Chi-square analyses indicated that performance of the Afla-20-Cup, Aflatest, EZ-Screen, OXOID, and SAM-A methods was not statistically different from that of the HV minicolumn. Agri-Screen results were not statistically different from those obtained with TLC.


Fiber-Specific Changes in White Matter Microstructure in Individuals With X-Linked Auditory Neuropathy.
Auditory neuropathy (AN) is the term used to describe a group of hearing disorders, in which the hearing impairment occurs as a result of abnormal auditory nerve function. While our understanding of this condition has advanced significantly over recent years, the ability to determine the site of lesion and the extent of dysfunction in affected individuals remains a challenge. To this end, we investigated potential axonal degeneration in the white matter tracts of the brainstem in individuals with X-linked AN. We hypothesized that individuals with X-linked AN would show focal degeneration within the VIII nerve and/or auditory brainstem tracts, and the degree of degeneration would correlate with the extent of auditory perceptual impairment. This was achieved using a higher-order diffusion magnetic resonance imaging (dMRI)-based quantitative measure called apparent fiber density as obtained from a technique called single-shell 3-tissue constrained spherical deconvolution and analyzed with the fixel-based analysis framework. Eleven subjects with genetically confirmed X-linked AN and 11 controls with normal hearing were assessed using behavioral and objective auditory measures. dMRI data were also collected for each participant. Fixel-based analysis of the brainstem region showed that subjects with X-linked AN had significantly lower apparent fiber density in the VIII nerve compared with controls, consistent with axonal degeneration in this region. Subsequent analysis of the auditory brainstem tracts specifically showed that degeneration was also significant in these structures overall. The apparent fiber density findings were supported by objective measures of auditory function, such as auditory brainstem responses, electrocochleography, and otoacoustic emissions, which showed VIII nerve activity was severely disrupted in X-linked AN subjects while cochlear sensory hair cell function was relatively unaffected. Moreover, apparent fiber density results were significantly correlated with temporal processing ability (gap detection task) in affected subjects, suggesting that the degree of VIII nerve degeneration may impact the ability to resolve temporal aspects of an acoustic signal. Auditory assessments of sound detection, speech perception, and the processing of binaural cues were also significantly poorer in the X-linked AN group compared with the controls with normal hearing. The results of this study suggest that the dMRI-based measure of apparent fiber density may provide a useful adjunct to existing auditory assessments in the characterization of the site of lesion and extent of dysfunction in individuals with AN. Additionally, the ability to determine the degree of degeneration has the potential to guide rehabilitation strategies in the future.


Exergaming, Exercise, and Gaming: Sharing Motivations.
Health professionals view exergame technologies as an alternative tool in therapeutic treatments and the promotion of physical activity. There is a growing body of work addressing the health benefits of exergaming; however, there is limited knowledge concerning user experience in this new context. If we aim to encourage participation in exergaming, we must first understand why gamers currently play exergames. Exergaming refers to the computer games that require players to perform some level of physical exertion to play. For this reason, the present study compares the motivations that encourage participation in three contexts (exercise, computer games, and exergaming) to identify key elements that support such participation. Survey instruments were administered in each context, and motivational components were addressed within self-determination theory. Findings suggest perceptions of enjoyment and feeling better after a session and participation within a social context are key factors that encourage participation in the three contexts. Participation in exergaming is also encouraged by perceptions of performing mild exercise while playing videogames. Exergamers might not experience an optimal challenge while playing, and this may lower their motivation. Participation in exercise is also encouraged by perceptions of being healthier and, in some instances, driven to avoid feelings of guilt. Gamers also play computer games encouraged by perceptions being in a better mood after session, although some gamers might also participate aiming to gain social acceptance.


Fluid resuscitation: a Defence Medical Services Delphi study into current practice.
A Delphi study was carried out to investigate recent changes in the fluid resuscitation of patients. A thirty member panel was selected primarily from the UK Defence Medical Services but also included contributors from other NATO members and civilian practice. The study was carried out in two rounds and achieved consensus on a range of statements relating to fluid resuscitation. Key recommendations are grouped by category. Statements reaching consensus included the use of adult intraosseous access, limited hypotensive resuscitation and goal directed therapy in trauma patients. Consensus was not achieved with respect to the selection of non-oxygen carrying synthetic colloids. The study provides a broad review of current practice and adds to previous consensus publications on fluid resuscitation.


Protective effect of carvacrol on acetic acid-induced colitis.
The pharmacological therapy for inflammatory bowel diseases continues to be problematic, and requires new alternative options. In this study, we tested the hypothesis that carvacrol (CAR), a phenolic monoterpene with anti-inflammatory and antioxidant activities, can treat experimental colitis in mice. C57BL/6 mice (n=8/group) were subjected to intrarectal administration of acetic acid (5%) to induce colitis. Mice were pretreated with CAR (25, 50 or 100mg/kg, p.o.) every 12h for three days prior to the induction. Abdominal hyperalgesia, macroscopic and microscopic colon damage, myeloperoxidase (MPO) activity, tumor necrosis factor (TNF)-α and interleukin (IL)-1β levels, oxidative stress markers, and antioxidant enzyme activities were evaluated. Pretreatment with all doses of CAR significantly decreased abdominal hyperalgesia and colon MPO activity and TNF-α and IL-1β levels. A reduction in macroscopic and microscopic damage (p<0.05) was observed at doses of 50 and 100mg/kg CAR. Pretreatment with CAR significantly reduced lipid peroxidation (for all doses) and increased sulfhydryl groups (at 100mg/kg). This effect was accompanied by a significant increase in catalase, superoxide dismutase, and glutathione peroxidase activities. These findings indicate that CAR protected mice from acetic acid-induced colitis by reducing inflammatory, nociceptive, and oxidative damages.


Individual resting-state alpha peak frequency and within-trial changes in alpha peak frequency both predict visual dual-pulse segregation performance.
Although sensory input is continuous, information must be combined over time to guide action and cognition, leading to the proposal of temporal sampling windows. A number of studies have suggested that a 10-Hz sampling window might be involved in the "frame rate" of visual processing. To investigate this, we tested the ability of participants to localize and enumerate 1 or 2 visual flashes presented either at near-threshold or full-contrast intensities, while recording magnetoencephalography. The inter-stimulus interval (ISI) between the 2 flashes was varied across trials. Performance in distinguishing between 1 and 2 flashes was linked to the alpha frequency, both at the individual level and trial-by-trial. Participants with a higher resting-state alpha peak frequency showed the greatest improvement in performance as a function of ISI within a 100-ms time window, while those with slower alpha improved more when ISI exceeded 100 ms. On each trial, correct enumeration (1 vs. 2) performance was paired with faster pre-stimulus instantaneous alpha frequency. Our results suggest that visual sampling/processing speed, linked to peak alpha frequency, is both an individual trait and can vary in a state-dependent manner.


Activation of MAPK kinase 9 induces ethylene and camalexin biosynthesis and enhances sensitivity to salt stress in Arabidopsis.
Mitogen-activated protein kinase (MAPK) cascades play important roles in regulating plant growth, development, and responses to various environmental stimuli. We demonstrate that MKK9, an MKK, is an upstream activator of the MPKs MPK3 and MPK6 both in vitro and in planta. Expression of active MKK9 protein in transgenic plants induces the synthesis of ethylene and camalexin through the activation of the endogenous MPK3 and MPK6 kinases. As a consequence, transcription of multiple genes responsible for ethylene biosynthesis, ethylene responses, and camalexin biosynthesis is coordinately up-regulated. The activation of MKK9 inhibits hypocotyl elongation in the etiolated seedlings. MKK9-mediated effects on hypocotyl elongation were blocked by the ethylene biosynthesis inhibitor, aminoethoxyvinylglycine, and ethylene receptor antagonist, Ag(+). Expression of active MKK9 protein enhances the sensitivity of transgenic seedlings to salt stress, whereas loss of MKK9 activity reduces salt sensitivity indicating a role for MKK9 in the salt stress response. The results reported here reveal that the MKK9-MPK3/MPK6 cascade participates in the regulation of the biosynthesis of ethylene and camalexin and may be an important axis in the stress responses of Arabidopsis.


Spontaneous closure of a left ventricle pseudoaneurysm following apical venting.
Cardiac surgery is the second most frequent aetiology of left ventricular pseudoaneurysm (LVP). Left ventricular apical venting is a recognized cause of LVP. Prompt surgical treatment is usually needed since there is a high risk of rupture and spontaneous closure is very rare. We describe a case of spontaneous closure of a left ventricle pseudoaneurysm following apical venting.


The precautionary principle: a dialectical reconsideration.
This essay examines an overlooked element of the precautionary principle: a prudent assessment of the long-range or remote catastrophes possibly associated with technological development must include the catastrophes that may take place because of the absence of such technologies. In short, this brief essay attempts to turn the precautionary principle on its head by arguing that, (1) if the long-term survival of any life form is precarious, and if the survival of the current human population is particularly precarious, especially given contemporary urban population densities, and (2) if technological innovation and progress are necessary in order rapidly to adapt humans to meet environmental threats that would otherwise be catastrophic on a large scale (e.g., pandemics of highly lethal diseases), then (3) the development of biomedical technologies in many forms, but in particular including human germ-line genetic engineering, may be required by the precautionary principle, given the prospect of the obliteration of humans in the absence of such enhanced biotechnology. The precautionary principle thus properly understood requires an ethos that should generally support technological innovation, at least in particular areas of biotechnology.


Metrizamide-enhanced computed tomography of intracranial arachnoid cysts.
Between July 1981 and August 1983 the authors studied 21 patients with intracranial arachnoid cysts using metrizamide-enhanced CT. With this method we are able to determine the degree of communication between the cysts and the surrounding subarachnoid space as well as to assess the evolving character of some of these lesions. This information will allow a more rational choice of surgical treatment.


SEA0400, a novel and selective inhibitor of the Na+-Ca2+ exchanger, attenuates reperfusion injury in the in vitro and in vivo cerebral ischemic models.
The effect of the newly synthesized compound 2-[4-[(2,5-difluorophenyl)methoxy]phenoxy]-5-ethoxyaniline (SEA0400) on the Na+-Ca2+ exchanger (NCX) was investigated and compared against that of 2-[2-[4-(4-nitrobenzyloxy)phenyl]ethyl]isothiourea (KB-R7943). In addition, the effects of SEA0400 on reperfusion injury in vitro and in vivo were examined. SEA0400 was extremely more potent than KB-R7943 in inhibiting Na+-dependent Ca2+ uptake in cultured neurons, astrocytes, and microglia: IC50s of SEA0400 and KB-R7943 were 5 to 33 nM and 2 to 4 microM, respectively. SEA0400 at the concentration range that inhibited NCX exhibited negligible affinities for the Ca2+ channels, Na+ channels, K+ channels, norepinephrine transporter, and 14 receptors, and did not affect the activities of the Na+/H+ exchanger, Na+,K+-ATPase, Ca2+-ATPase, and five enzymes. SEA0400, unlike KB-R7943, did not inhibit the store-operated Ca2+ entry in cultured astrocytes. SEA0400 attenuated dose- dependently paradoxical Ca2+ challenge-induced production of reactive oxygen species, DNA ladder formation, and nuclear condensation in cultured astrocytes, whereas it did not affect thapsigargin-induced cell injury. Furthermore, administration of SEA0400 reduced infarct volumes after a transient middle cerebral artery occlusion in rat cerebral cortex and striatum. These results indicate that SEA0400 is the most potent and selective inhibitor of NCX, and suggest that the compound may exert protective effects on postischemic brain damage.


Criteria for compliance: Centers for Medicare & Medicaid Services pain management at F-Tag 309.
Outline the key points and list the criteria for compliance with the new Centers for Medicare & Medicaid Services (CMS) pain management at F-Tag 309. Live symposium presentation based on clinical practice and research and current clinical guidelines. In March 2009, CMS implemented revised guidelines for long-term care surveyors at F-Tag 309, Quality of Care, including a new general investigative protocol and pain-management guidance. While the regulations have remained the same, the way surveyors interpret pain management has changed. By understanding the criteria surveyors will use to determine F-Tag 309 deficiencies, consultant pharmacists can educate other interdisciplinary team members to improve pain management practices in long-term care.


Expression and subcellular distribution of the active form of c-Src tyrosine kinase in differentiating human endometrial stromal cells.
Decidual growth factors and locally produced cytokines are thought to activate specific phosphorylation signalling pathway(s), thereby eliciting a variety of decidual functions. We have previously reported the activation of c-Src tyrosine kinase during ovarian steroid-induced decidualization of cultured human endometrial stromal cells. As chicken c-Src is known to be activated upon dephosphorylation of tyrosine 527 (Y527, corresponding to Y530 in human), we here employed a monoclonal antibody, clone 28, directed against the active form of human c-Src whose Y530 is dephosphorylated, and investigated whether c-Src became dephosphorylated at Y530 and thereby activated during decidualization. We found that the active form of c-Src was up-regulated and demonstrated increased kinase activity during in-vitro decidualization. Immunohistochemistry revealed that decidual cells in early pregnancy decidua were intensely stained with clone 28 when compared with the stromal cells in the non-pregnant endometrium. Moreover, the active form of c-Src translocated from a perinuclear region to the cytoplasm upon decidualization. Thus, the Y530 dephosphorylation, kinase activation, and subcellular translocation of c-Src may be intracellular signalling events associated with decidualization in vivo as well as in vitro.