Prostaglandin E2 content in residual gastric juice reflects endoscopic damage to the gastric mucosa after naproxen sodium administration.
The diagnostic potential of residual gastric juice for development of naproxen sodium-induced mucosal damage has not been explored. We studied prostaglandin E2 (PGE2) content in residual gastric juice before and after naproxen sodium administration and assessed relationships with endoscopic mucosal damage. Thirty volunteers received the recommended over-the-counter dose (660 mg/day) of naproxen sodium or placebo in this 7-day, double-blind, endoscopically controlled, cross-over study. PGE2 concentration in gastric juice did not increase after placebo; naproxen significantly reduced PGE2 concentration (p < 0.001). In three subjects in whom no endoscopic changes occurred after naproxen administration, PGE2 concentration increased by 14%. In seven subjects who developed hemorrhagic changes, PGE2 concentration declined by 50% (p = 0.08). In 20 subjects who developed numerous hemorrhagic and erosive changes within the antral mucosa, PGE2 concentration declined by 70% (p < 0.001). The starting PGE2 value in subjects with severe mucosal hemorrhagic and erosive changes after naproxen was almost eightfold higher than in subjects who did not develop mucosal damage (p = 0.007) and 67% higher than in subjects with hemorrhagic changes only (p = 0.25). PGE2 measurement in residual gastric juice, aspirated before and after nonsteroidal antiinflammatory drug treatment, may be useful in monitoring mucosal damage and may identify patients who are likely to develop endoscopic mucosal changes.


Subthalamic nucleus stimulation in Parkinson's disease.
Deep brain stimulation (DBS) is an effective surgical treatment for advanced Parkinson's disease (PD), with significant advantages in morbidity-mortality and quality of life when compared to lesion techniques such as thalamotomy and/or pallidotomy. The procedure is indicated in patients with severe resting tremor, unresponsive to conventional medical treatment or with motor complications. The most commonly reported complications in the intra- and post-surgical period are aborted procedure, misplaced leads, intracranial haemorrhage, seizures and hardware complications, whereas in the long-term period, cognitive and psychiatric complications can be observed. The most important eligibility criteria for DBS are: a correct diagnosis of idiopathic PD, severity of illness, a consistent levodopa response and absence of cognitive impairment. Chronological age and mood disorders may be relative contraindications to be individually evaluated. Tremor, rigidity dystonias and dyskinesias improve dramatically after DBS; freezing, postural instability and falls remain unchanged, whereas verbal fluency and dysarthria are known to worsen.


Effects of angiotensin converting enzyme inhibitor and calcium channel blocker on normoxic and hypoxic pulmonary vascular tone in unanesthetized sheep.
We evaluated the effects of captopril and nifedipine on normoxic and hypoxic pulmonary vascular tone in unanesthetized sheep. Infusion of captopril (10 micrograms/kg/min) in normoxia revealed a tendency to increase the mean pulmonary arterial pressure (Ppa) and the pulmonary vascular resistance (PVR) following the systemic vasodilation. A statistically significant increase was reached by 20 minutes. Hypoxia of 10% oxygen in nitrogen produced a prominent pulmonary hypertensive response. Captopril significantly decreased the hypoxic values of Ppa and PVR from 20.3 +/- 1.3 to 17.1 +/- 1.1 mmHg (p less than 0.01) and from 4.31 +/- 0.45 to 3.49 +/- 0.45 mmHg/L/min (p less than 0.01), respectively. Infusion of nifedipine (10 micrograms/kg/min) in normoxia caused an increase in Ppa from 15.5 +/- 0.9 to 18.9 +/- 1.0 mmHg (p less than 0.01), but not in PVR. This elevation in Ppa was considered to be derived from the significant increase in the cardiac output. Nifedipine significantly decreased the hypoxic values of Ppa and PVR from 21.3 +/- 1.5 to 19.3 +/- 1.5 mmHg (p less than 0.05) and from 3.88 +/- 0.30 to 27.3 +/- 0.13 mmHg/L/min (p less than 0.01), respectively. Captopril and nifedipine produced systemic hypotensive responses during both normoxic and hypoxic ventilation. It is concluded that both captopril and nifedipine are potent pulmonary vasodilating drugs in animal subjects with a hypoxic condition and that they might be useful in the clinical vasodilator therapy of hypoxic pulmonary hypertension in man.


Impact of Singly Occupied Molecular Orbital Energy on the n-Doping Efficiency of Benzimidazole Derivatives.
We investigated the impact of singly occupied molecular orbital (SOMO) energy on the n-doping efficiency of benzimidazole derivatives. By designing and synthesizing a series of new air-stable benzimidazole-based dopants with different SOMO energy levels, we demonstrated that an increase of the dopant SOMO energy by only ∼0.3 eV enhances the electrical conductivity of a benchmark electron-transporting naphthalenediimide-bithiophene polymer by more than 1 order of magnitude. By combining electrical, X-ray diffraction, and electron paramagnetic resonance measurements with density functional theory calculations and analytical transport simulations, we quantitatively characterized the conductivity, Seebeck coefficient, spin density, and crystallinity of the doped polymer as a function of the dopant SOMO energy. Our findings strongly indicate that charge and energy transport are dominated by the (relative) position of the SOMO level, whereas morphological differences appear to play a lesser role. These results set molecular-design guidelines for next-generation n-type dopants.


[Diagnosis and treatment of 178 patients with carcinoma of the head of pancreas].
To improve the diagnosis and treatment of carcinoma of head of pancreas. A retrospective study was carried out to evaluate 178 patients suffering from carcinoma of head of pancreas. Pain in the epigastrium and obstructive jaundice were observed in 70% and 74.2% of these 178 patients, both of which were of significance (P < 0.001) between stage I, II and stage III, IV disease. Only 18% of patients had pain in the back, 81.3% of whom belonged to the stage IV category. The detection rate of the tumor by B-ultrasound, CT and MRI were 74.2%, 87.3% and 85.5%, respectively. The success rate of pancreatoduodenectomy was 10.1%. The postoperative 1-, 3- and 5-year survival rates were 67.5%, 36% and 5.6%. Internal drainage was performed in 115 patients. The median survival time was 7 months in patients with unresectable tumor who received radiotherapy and/or chemotherapy. Pain in the epigastrium and obstructive jaundice are the most common symptoms. Hyperglycemia is the most common complication. Pain in the back implies an advanced lesion. CT is the most important way of diagnosis and the combination of B-ultrasound, CT and MRI may improve the rate of diagnosis up to 96.6%. By now, pancreaticoduodenectomy is still the only effective treatment for the carcinoma of head of pancreas and internal drainage is an important palliative measure.


Clinical characteristics of Kraepelinian schizophrenia: replication and extension of previous findings.
Subtypologies of schizophrenia based on cross-sectional criteria, such as the nomenclature of the DSMs, have not been successful in identifying valid diagnostic subgroups among patients with schizophrenia. A subtypology that uses criteria to classify individuals on the basis of longitudinal deficits in self-care may identify a more valid subgroup of schizophrenic patients. This study describes the clinical characteristics of a group of schizophrenic patients identified on the basis of a longitudinal criterion: at least 5 years of continuous and complete dependence on others for obtaining and maintaining the basic necessities of life, including food, clothing, and shelter. Sixty-one "Kraepelinian" schizophrenic inpatients, when compared to 80 non-Kraepelinian schizophrenic inpatients who were similar in years of illness, age, and education, demonstrated more severe negative symptoms and more severe formal thought disorder; yet the severity of their delusions, hallucinations, and bizarre behavior did not differ significantly. None of the Kraepelinian patients and eight non-Kraepelinian patients met DSM-III-R criteria for schizoaffective disorder. Data from this replication study suggest that Kraepelinian schizophrenic patients, identified on the basis of a longitudinal course characterized by severe dysfunctions in self-care, may represent an alternative, and possibly more valid, method of subtyping schizophrenia.


Genetic ablation of the aryl hydrocarbon receptor causes cigarette smoke-induced mitochondrial dysfunction and apoptosis.
Cigarette smoke is the primary risk factor for chronic obstructive pulmonary disease (COPD). Alterations in the balance between apoptosis and proliferation are involved in the etiology of COPD. Fibroblasts and epithelial cells are sensitive to the oxidative properties of cigarette smoke, and whose loss may precipitate the development of COPD. Fibroblasts express the aryl hydrocarbon receptor (AhR), a transcription factor that attenuates pulmonary inflammation and may also regulate apoptosis. We hypothesized the AhR would prevent apoptosis caused by cigarette smoke. Using genetically deleted in vitro AhR expression models and an established method of cigarette smoke exposure, we report that AhR expression regulates fibroblasts proliferation and prevents morphological features of apoptosis, including membrane blebbing and chromatin condensation caused by cigarette smoke extract (CSE). Absence of AhR expression results in cleavage of PARP, lamin, and caspase-3. Mitochondrial dysfunction, including cytochrome c release, was associated with loss of AhR expression, indicating activation of the intrinsic apoptotic cascade. Heightened sensitivity of AhR-deficient fibroblasts was not the result of alterations in GSH, Nrf2, or HO-1 expression. Instead, AhR(-/-) cells had significantly less MnSOD and CuZn-SOD expression, enzymes that protects against oxidative stress. The ability of the AhR to suppress apoptosis was not restricted to fibroblasts, as siRNA-mediated knockdown of the AhR in lung epithelial cells also increased sensitivity to smoke-induced apoptosis. Collectively, these results suggest that cigarette smoke induced loss of lung structural support (i.e. fibroblasts, epithelial cells) caused by aberrations in AhR expression may explain why some smokers develop lung diseases such as COPD.


The posterior operative approach for cervical radiculopathy.
Cervical disc disease includes acute herniation and chronic disc degeneration with secondary changes in the associated bone. The latter may lead to the spectrum of cervical spondylitic stenosis, which is considered to be multilevel and may be more of a bony disease. Clinically, cervical disc disorders can be divided into several disorders. The disorder of true cervical radiculopathy is associated with lateral compression of the nerve root. When this condition is due to a lateral soft disc herniation or lateral bony stenosis, the posterior cervical laminoforaminotomy is commonly used. It is a procedure that works extremely well in the vast majority of patients and there is no risk of spinal instability; therefore, no fusion is required. The details of operative care have been described. In patients who have persistent radicular problems after a failed anterior cervical interspace procedure, the posterior cervical laminoforaminotomy with posterior wiring and fusion is a simple and effective operative option.


Collaboration between the general dentist and orthodontist: an essential partnership to ensure orthodontic success.
Orthodontic therapy can significantly improve a patient's quality of life in a number of ways. Benefits of orthodontic therapy include a beautiful smile, increased self-confidence, and better overall dental and periodontal health. Collaboration and communication between the general dental team and the orthodontic team are essential elements to ensuring successful outcomes for orthodontic patients. This partnership starts from the time of the initial referral and continues through the retention stage of treatment when all tooth movement is complete. This overview article describes keys to implementing and executing a team-oriented approach towards orthodontic treatment.


Serial Inhibin B Measurements in Boys with Congenital Monorchism Indicate Compensatory Testicular Hypertrophy in Early Infancy.
Congenital monorchism is considered a condition in which an initially normal testis has existed but subsequently atrophied and disappeared due to a third trimester catastrophe (presumably torsion). Since inhibin B concentrations appear related to Sertoli and germ cells number, we evaluated pre- and postoperative inhibin B of boys with congenital monorchism to determine whether the well-known hypertrophy of the contralateral testis was reflected in inhibin B concentrations. Twenty-seven boys consecutively diagnosed with congenital monorchism (median age 12 months) underwent follow-up with reproductive hormones 1 year postoperatively (median age 25 months). The results were compared with inhibin B of 225 boys with congenital nonsyndromic unilateral cryptorchidism, by converting values to multiple of the median (MoM) for age in normal boys. Ten boys (37%) had blind-ending vessels and ductus deferens (vanished testis) and the remaining (63%) had testicular remnants. At the time of diagnostic procedure, monorchid boys did not have significantly lower inhibin B (median 114, range 20-208) than unilateral cryptorchid boys (136, 47-393) (p = 0.27). During follow-up, MoM values of inhibin B increased in monorchid boys (median 0.59 to 0.98) and in unilateral cryptorchid boys (0.69 to 0.89) (both p < 0.0001). Compared with the concentration at surgery, an additional 44% monorchid boys had inhibin B MoM values higher than 1.0, whereas only additional 23% of unilateral cryptorchid boys exhibited such values (p = 0.04). Generally, inhibin B MoM values were normalized during follow-up in boys with congenital monorchism, reflecting compensatory hypertrophy within the first 2.5 years of life. The compensatory capacity to increase was better in monorchism than in unilateral cryptorchidism.


Resveratrol activates GABAA and/or glycine receptors on substantia gelatinosa neurons of the subnucleus caudalis in mice.
Although a number of studies have reported that resveratrol has analgesic effects, the direct effect of resveratrol on substantia gelatinosa (SG) neurons of the trigeminal subnucleus caudalis (Vc) involved in orofacial nociceptive transmission has not been clearly examined. Thus, the objective of this study was to investigate effects of resveratrol on SG neurons of Vc in mice using a whole-cell patch-clamp technique. Resveratrol (500 μM) induced repeatable inward currents without desensitisation. Resveratrol-induced inward currents were shown in a concentration-dependent manner. Resveratrol-induced responses were sustained in the presence of tetrodotoxin, 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and DL-2-Amino-5-phosphonovaleric acid (DL-AP5). However, resveratrol-induced inward currents were suppressed in the presence of picrotoxin and strychnine. These results indicate that resveratrol can directly act on SG neurons of Vc with possible inhibitory effects on SG neurons through activation of GABAA receptors and/or glycine receptors. Thus, resveratrol can be a potential therapeutic for orofacial pain modulation.


Cardiac Autonomic Function at Baseline and under Stress and Its Relationship to Circulatory Markers of Inflammation in Obese Compared to Nonobese Children: A Pilot Study.
The autonomic nervous system (ANS) provides neurogenic control of inflammatory reactions. ANS changes in obesity may result in inflammation. This study sought to gain insight into cardiac autonomic dysfunction and inflammation in childhood obesity, and to gather pilot data on the potential relationship between altered ANS and inflammation. Fifteen obese children and adolescents without metabolic complications and 15 nonobese controls underwent heart rate variability and impedance cardiography testing during rest, mental stress, and physical stress. Inflammatory cytokines and immune reactivity were measured. There was no statistically significant difference between groups in cardiac ANS testing at rest or in response to stress. Median high-sensitivity C-reactive protein (hsCRP) was higher in the obese group [obese 2.6 mg/l (IQR 1.6-11.9); nonobese 0.3 mg/l (IQR 0.2-0.7); p < 0.001]. Interleukin-6 and tumour necrosis factor-α were similar between groups. Immune reactivity testing (in vitro Toll-like receptor stimulation) revealed a strong, but comparable, inflammatory response in both groups. Obese children and adolescents without metabolic complications did not have cardiac ANS dysfunction. While hsCRP was elevated, systemic cytokines were not raised. Compared to prior studies, which often focused on children with obesity and its complications, it is encouraging that obese children without metabolic complications may not yet have autonomic dysfunction.


Effect of topical 3% diquafosol sodium on eyes with dry eye disease and meibomian gland dysfunction.
To prospectively evaluate the effect of topical diquafosol sodium on eyes with dry eye disease (DED) and meibomian gland dysfunction (MGD). The subjects were consecutive patients diagnosed with both DED and MGD at Inouye Eye Hospital between March and September of 2016. The subjects were administered topical 3% diquafosol sodium ophthalmic solution six times a day for 3 months. At each study visit, subjects underwent slit-lamp examination and completed MGD symptoms and dry eye-related quality of life score (DEQS) questionnaires. Meibum quality (meibum score) and meibomian gland loss (meiboscore) were evaluated. Tear lipid layer thickness was measured in both eyes with an ocular surface interferometer immediately after clinic arrival and 20 minutes after instillation of one drop of topical diquafosol. Thirteen patients (3 men, 10 women) with a mean age of 69.5±8.3 years completed the 3-month study. The number of telangiectasia and plugged meibomian gland orifices significantly decreased from baseline after 1 month of diquafosol use. The meibum score and the meiboscore significantly decreased from baseline at 3 months. Also, the lipid layer thickness was greater after diquafosol administration than before administration at baseline and 1, 2, and 3 months by 12.2, 11.5, 9.5, and 17.0 nm, respectively, but this difference was only significant at 3 months (p=0.039). The DEQS ocular symptom (p=0.065) and MGD questionnaire (p=0.081) scores tended to be lower than baseline at 3 months. Diquafosol sodium ophthalmic solution improves DED- and MGD-related signs in eyes with MGD.


Anaplasma capra in sheep and goats on Corsica Island, France: A European lineage within A. capra clade II?
Anaplasmosis is a tick-transmitted disease due to several species of the genus Anaplasma. In 2019, we demonstrated the presence of Anaplasma capra in two deer species at a zoological park in mainland France. As we suspected its presence in Corsica, we surveyed 11 geographically distant sheep or goat farms. Using molecular tools such as nested PCR targeting 16S ribosomal RNA (rRNA), citrate synthase (gltA) and heat-shock protein (groEL) genes, we detected the presence of A. capra on 5/11 farms, in 26/108 blood samples (24%), in sheep as well as in goats. Genotyping and phylogenetic analysis of A. capra revealed that isolates from Corsica island grouped closely with A. capra isolates reported in red deer and swamp deer from a zoological reserve in mainland France, as well as in roe deer from Spain, in a separate and well supported clade within A. capra clade II. This third report of the tick-borne bacterium A. capra in Europe suggests a potentially larger presence of this pathogen on the European continent, on domestic, native as well as wild ruminants, a broad host range already described in Asian countries for this species.


Coarse-Grained Simulations of Aqueous Thermoresponsive Polyethers.
Thermoresponsive polymers can change structure or solubility as a function of temperature. Block co-polymers of polyethers have a response that depends on polymer molecular weight and co-polymer composition. A coarse-grained model for aqueous polyethers is developed and applied to polyethylene oxide and polyethylene oxide-polypropylene oxide-polyethylene oxide triblock co-polymers. In this model, no interaction sites on hydrogen atoms are included, no Coulombic interactions are present, and all interactions are short-ranged, treated with a combination of two- and three-body terms. Our simulations find that The triblock co-polymers tend to associate at temperatures above 350 K. The aggregation is stabilized by contact between The hydrophobic methyl groups on The propylene oxide monomers and involves a large, favorable change in entropy.


Functional and molecular characterisation of lactic acid transport in bovine articular chondrocytes.
Chondrocytes, which control the turnover of cartilage, undergo predominantly glycolytic metabolism due to the avascular nature of the tissue. This will result in high levels of lactic acid production, and this lactic acid must leave the cells for their normal intracellular pH to be maintained. However to date the mechanism by which lactic acid is removed from the chondrocytes has not been elucidated. In the present study lactic acid transport has been characterised using the intracellular pH-sensitive fluorimetric dye BCECF to measure intracellular pH (pH(i)). Addition of extracellular lactic acid-induced an acidification which was sensitive to alpha-cyano-4-hydroxycinnamate (alpha-CHC) and phloretin indicating the involvement of isoform(s) of the monocarboxylate transporter (MCT) family. The results studies of transport kinetics were consistent with the MCT4 isoform (K(m) 14.1mM), common to other glycolytic cells. Western blotting confirmed that MCT4 was the predominantly expressed isoform, although both MCT1 and MCT4 transcripts were present when cells were assayed by RT-PCR. Through effects on pH(i), the activity of this transporter may therefore modify cartilage turnover.


Involvement of insulin receptor substrate 2 in mammary tumor metastasis.
The insulin receptor substrate (IRS) proteins are adaptor molecules that integrate signals generated by receptors that are implicated in human breast cancer. We investigated the specific contribution of IRS-2 to mammary tumor progression using transgenic mice that express the polyoma virus middle T antigen (PyV-MT) in the mammary gland and IRS-2-null (IRS-2(-/-)) mice. PyV-MT-induced tumor initiation and growth were similar in wild-type (WT) and IRS-2(-/-) mice. However, the latency and incidence of metastasis were significantly decreased in the absence of IRS-2 expression. The contribution of IRS-2 to metastasis is intrinsic to the tumor cells, because IRS-2(-/-) mammary tumor cells did not metastasize when grown orthotopically in the mammary fat pads of WT mice. WT and IRS-2(-/-) tumors contained similar numbers of mitotic cells, but IRS-2(-/-) tumors had a higher incidence of apoptosis than did WT tumors. In vitro, IRS-2(-/-) mammary tumor cells were less invasive and more apoptotic in response to growth factor deprivation than their WT counterparts. In contrast, IRS-1(-/-) tumor cells, which express only IRS-2, were highly invasive and were resistant to apoptotic stimuli. Collectively, our findings reveal an important contribution of IRS-2 to breast cancer metastasis.


Role of EP4 receptor and prostaglandin transporter in prostaglandin E2-induced alteration in colonic epithelial barrier integrity.
Prostaglandin E(2) (PGE(2)) is a proinflammatory lipid mediator produced in excess in inflammatory bowel disease (IBD). PGE(2) couples to and signals via four different E-prostanoid (EP) receptors, namely EP1, EP2, EP3, and EP4. In this study, we determined a role for PGE(2) and EP4 receptors in altering colonic epithelial barrier integrity. In healthy colonic mucosa, EP4 receptors were localized on apical plasma membrane of epithelial cells at the tip of mucosal folds, whereas, in patients with IBD and in rats with dextran sodium sulfate (DSS)-induced colitis, they were diffusely overexpressed throughout the mucosa. Similarly, expression of EP4 receptor was polarized in T84 colonic epithelial monolayer and mimics the normal epithelium. Apical exposure of T84 monolayer with high levels of PGE(2) decreased barrier integrity, which was abrogated by an EP4 receptor antagonist. To reveal the mechanism of vectorial transport of basally produced PGE(2) toward apical EP4 receptors, we identified prostaglandin transporters (PGT) in human colonic epithelia. PGT were least expressed on epithelial cells at the colonic mucosal folds of control subjects but overexpressed in epithelial cells of patients with IBD or animals with DSS-induced colitis. T84 monolayer also expressed PGT, which increased twofold following stimulation with TNF-α. Importantly, in T84 monolayer stimulated with TNF-α, there was a corresponding increase in the uptake and vectorial transport of (3)H-PGE(2) to the apical surface. Knockdown or pharmacological inhibition of PGT significantly decreased vectorial transport of (3)H-PGE(2). These studies unravel a mechanism whereby EP4 receptor and PGT play a role in PGE(2)-induced alteration of epithelial barrier integrity in colitis.


Post-concussive mTBI in Student Athletes: MRI Features and Machine Learning.
Purpose: To determine and characterize the radiomics features from structural MRI (MPRAGE) and Diffusion Tensor Imaging (DTI) associated with the presence of mild traumatic brain injuries on student athletes with post-concussive syndrome (PCS). Material and Methods: 122 student athletes (65 M, 57 F), median (IQR) age 18.8 (15-20) years, with a mixed level of play and sports activities, with a known history of concussion and clinical PCS, and 27 (15 M, 12 F), median (IQR) age 20 (19, 21) years, concussion free athlete subjects were MRI imaged in a clinical MR machine. MPRAGE and DTI-FA and DTI-ADC images were used to extract radiomic features from white and gray matter regions within the entire brain (2 ROI) and the eight main lobes of the brain (16 ROI) for a total of 18 analyzed regions. Radiomic features were divided into five different data sets used to train and cross-validate five different filter-based Support Vector Machines. The top selected features of the top model were described. Furthermore, the test predictions of the top four models were ensembled into a single average prediction. The average prediction was evaluated for the association to the number of concussions and time from injury. Results: Ninety-one PCS subjects passed inclusion criteria (91 Cases, 27 controls). The average prediction of the top four models had a sensitivity of 0.80, 95% CI: [0.71, 0.88] and specificity of 0.74 95%CI [0.54, 0.89] for distinguishing subjects from controls. The white matter features were strongly associated with mTBI, while the whole-brain analysis of gray matter showed the worst association. The predictive index was significantly associated with the number of concussions (p < 0.0001) and associated with the time from injury (p < 0.01). Conclusion: MRI Radiomic features are associated with a history of mTBI and they were successfully used to build a predictive machine learning model for mTBI for subjects with PCS associated with a history of one or more concussions.


Chemoport-skin erosion: our experience.
Chemoports are totally implantable venous access devices, which are retained over long periods of time to facilitate chemotherapy administration. Skin erosion is a rare complication wherein there is breach in the skin overlying the septum. This study reports the author's experience of skin erosion in three cases. Ports were explanted in all cases. Skin incision for port placement should be placed away from the access site and repeated access at the same point must be avoided to lessen the incidence of skin erosions.


Murine Brca1: sequence and significance for human missense mutations.
We have cloned and sequenced a mouse homologue of the human breast and ovarian cancer susceptibility gene, BRCA1. The predicted mouse Brca1 protein is composed of 1812 amino acids. The murine protein is 60% identical and 72% similar to the human BRCA1 protein. Two regions of high homology have been identified between the two proteins. First is the Cys3-His-Cys4 type zinc-finger domain that is identical between the two proteins. The second region is defined by 115 amino acids near the carboxyl end of the Brca1 protein that is 83% identical to human BRCA1 sequence. Seven of eight amino acids involved in human missense mutations that are associated with the disease were found to be conserved between the two species. In contrast, most of the amino acids that are involved in polymorphic variations were not conserved. We therefore propose that the interspecies conservation of predicted amino acid sequences can be used as an additional criterion to determine the significance of human missense mutations.


Autonomous learning by simple dynamical systems with delayed feedback.
A general scheme for the construction of dynamical systems able to learn generation of the desired kinds of dynamics through adjustment of their internal structure is proposed. The scheme involves intrinsic time-delayed feedback to steer the dynamics towards the target performance. As an example, a system of coupled phase oscillators, which can, by changing the weights of connections between its elements, evolve to a dynamical state with the prescribed (low or high) synchronization level, is considered and investigated.


Putting the search for genes in perspective.
The sequencing of the human genome has been heralded by both the mass media and scientists as a breakthrough that will allow the detection of individuals at increased risk for common diseases and the tailoring of drugs to an individual's genetic profile in order to prevent disease. Sequencing is likely to benefit those at risk of developing rare diseases in which inherited mutations in a single gene play a major causal role. In the vast majority of people with common diseases, however, genotypes at many different loci, as well as environmental exposures, must be simultaneously present before disease appears. Elucidating the genes involved will prove elusive. In addition to the large number, different combinations account for a particular disease. Most of the genotypes that contribute to the constellation of necessary genes are uncommon and will be difficult to find. Common genotypes may confer susceptibility but will be weak predictors of disease. Because of the difficulty of discovering genes for common diseases, designing therapies will also prove difficult. More attention to environmental risk factors for particular diseases will have greater yield than a genetic search, but this too will be difficult because of environmental-genetic and other interactions. The search for risk factors for particular diseases neglects the political and social milieu in which individuals swim or sink and in which all diseases occur.


[Mechanism of action of sympathetic and parasympathetic neuromediators at the level of the heart cell: use of photosensitive molecules].
We have shown in the first part of this work, how pharmacological technics can be associated to electrophysiological measurements, to study the action of neurotransmitters on the excitation-contraction coupling in cardiac cells. However, to better understand their mechanism of action, it is necessary to have informations about the link between the activation of the receptor and the conductance changes. Kinetics measurements have been very useful to investigate this problem at the nicotinic cholinergic receptor. This study was performed with technics such as iontophoresis, voltage relaxations, noise analysis and recently patch clamp measurements. Nicotinic responses are very fast (in the order of the msec) and are however the best known. The binding of the agonist to the receptor would lead to the opening of a channel only by molecular conformation change. By comparison, beta-adrenergic and muscarinic responses in heart or smooth muscle can be considered as "slow responses" because they are thought to be mediated by intracellular biochemical steps. We have developed a new technique using photosensitive compounds, which allows to jump the extra- or intracellular concentration of some active molecules. The experiments have been performed on frog atrial fibers, in current or voltage clamp conditions using a double sucrose gap technique. Various photochemical reactions have been exploited. The photoisomerization of an azobenzene derivative (Bis-Q) allows to study the muscarinic-induced potassium conductance. Bis-Q binds to muscarinic receptors and blocks the effect of agonists. These drugs have the additional property that their cis and trans configuration have different potencies. The photoisomerization cis----trans or trans----cis is obtained a few msec after a 1 msec duration light flash (respectively visible or UV), and then induces a concentration jump of antagonist near the receptor. The results show that the potassium conductance change has a slow relaxation time constant (tau = 500 msec.) and this suggest rather successive intracellular steps than the opening of a channel directly linked to the receptor. Cyclic nucleotides are considered as the intracellular messengers for various neurotransmitters or hormones. Our photochemical technique allows to jump the intracellular concentration of cAMP and cGMP in a few msec. cAMP (or cGMP) orthonitrobenzyl derivatives are able to penetrate cell membrane without injection and have no effect up to 100 microM. A UV flash (1 msec duration) induces a photolysis of the derivative and generates instantaneously cAMP (or cGMP) inside the cell.(ABSTRACT TRUNCATED AT 400 WORDS)


Recirculation subtraction for analysis of left-to-right-cardiac shunts: concise communication.
The object of this study is to improve the techniques for describing the lung dilution curve for shunt quantification by separating the effects of systemic recirculation on the curve form those of direct shunt return. The time of the systemic recirculation peak was estimated by determination of transit times from the right and left ventricles and lung. A gamma variate fit based on the distribution of points at that segment was applied to the recirculation curve and subtracted from the original lung dilution curve. Similar gamma variate fitting was performed for both primary and shunt curves. Rather than fitting the gamma variate of the shunt curve by the leading edge only, a larger portion could now be used since the trailing edge of the curve is clearer following recirculation subtraction. The algorithm is completely automatic, requiring no operator intervention or selection of curve-fitting regions. The correlation coefficient for comparison of the dilution-curve analysis with oximetry determinations was 0.92 in a series of 29 patients.


A retrospective analysis of the registered care technologist (RCT) proposal.
This article reviews, in retrospect, the Registered Care Technologist proposal previously advanced by the American Medical Association. It argues that an analysis of this proposal is a useful way of understanding interest group theory. Further, it makes a case for nurses in general and Black nurses in particular to understand this theory from an economic perspective. Finally, it urges all nurses to continue to collectively utilize power.


Nitrogen and COD removal from domestic and synthetic wastewater in subsurface-flow constructed wetlands.
Comparisons of the performance of constructed-wetland systems (CWs) for treating domestic wastewater in the laboratory and field may use pathogen-free synthetic wastewater to avoid regulatory health concerns. However, little to no data are available describing the relative treatment efficiencies of CWs to both actual and synthetic domestic wastewaters so as to enable such comparison. To fill this gap, treatment performances with respect to organics (chemical organic demand; COD) and nitrogen (ammonium and nitrate) removal from domestic (septic tank) and a similar-strength synthetic wastewater under planted and non-planted subsurface-flow CWs are determined. One pair of CWs was planted with cattails in May 2008, whereas the adjacent system was non-planted. Collected septic tank or synthesized wastewater was allowed to gravity feed each CWs, and effluent samples were collected and tested for COD and nitrogen species regularly during four different periods over six months. Overall, statistically significant greater removal of COD (-12%) and nitrogen (-5%) occurred from the synthetic as compared with the domestic wastewater from the planted and non-planted CWs. Effluent BOD5/COD ratios from the synthetic wastewater CWs averaged nearly twice that from the domestic wastewater CWs (0.17 vs 0.10), reflecting greater concentrations of readily degraded compounds. That removal fractions were consistent across the mid-range loading rates to the CWs suggests that the synthetic wastewater can be used in testing laboratory CWs with reasonable success in application of their results to the field.


Quality improvement related to radiation safety chest radiography in the NICU.
Discussion includes radiation safety and radiographic quality management, continual quality improvement processes, and management review over a three year period. The results of radiation safety and radiographic quality audits conducted on random samples of chest radiographs are included. Specific measures and improvement strategies are presented as they relate to "babygrams" patient positioning, shielding, collimation, exposure technique, exposure index, and patient holding by NICU staff. Discussion of the change management process related to physician ordering, radiologic technologist training, and interdepartmental collaboration and team building.


Concordance with clinical practice guidelines for adjuvant chemotherapy in patients with stage I-III colon cancer: experience in 2 Canadian provinces.
Clinical practice guidelines (CPGs) for the adjuvant treatment of colorectal cancer were published by the National Institutes of Health in 1991. The American Society of Clinical Oncology and Cancer Care Ontario have recommended adjuvant chemotherapy for patients with high-risk stage II colon cancer. We evaluated differences in concordance with guidelines in the treatment of patients with stage I-III colon cancer in the Canadian provinces of Newfoundland and Labrador and Ontario. We assessed clinical data and treatment from January 1999 to December 2000 for 130 patients from Newfoundland and Labrador and 315 patients from Ontario who had stage I-III colon cancer. The primary outcome was concordance with guidelines for adjuvant treatment. We evaluated factors affecting the use of chemotherapy in patients with stage II disease. No patients received adjuvant therapy for stage I disease. Forty-five of 52 patients (87%) in Newfoundland and Labrador and 108 of 115 patients (94%) in Ontario received adjuvant chemotherapy for stage III colon cancer. Twenty of 55 patients (36%) in Newfoundland and Labrador and 44 of 116 patients (38%) in Ontario received adjuvant therapy for stage II disease. Eighteen of 41 patients (44%) in Newfoundland and Labrador and 30 of 53 patients (57%) in Ontario with high-risk features received adjuvant treatment, which was significantly higher than patients without high-risk features. There was a strong trend toward using chemotherapy in patients with stage II disease who were 50 years or younger, independent of high-risk status. Concordance with CPGs for adjuvant chemotherapy in patients with stage II colon cancer was not optimal. This may reflect selection bias among referring surgeons, a paucity of level-I evidence and the belief that other factors such as age may play a role in predicting outcome.


Efficacy of Beraprost Sodium Combined with Sildenafil and Its Effects on Vascular Endothelial Function and Inflammation in Patients Experiencing Left Heart Failure Complicated with Pulmonary Arterial Hypertension.
BACKGROUND To explore the efficacy of beraprost sodium combined with sildenafil and its effects on the vascular endothelial function and inflammation in left heart failure patients complicated with pulmonary arterial hypertension. MATERIAL AND METHODS A total of 80 patients with left heart failure complicated with pulmonary arterial hypertension was enrolled as the subjects of this study and assigned into an observation group (n=40) and a control group (n=40) using a random number table. The changes in pulmonary arterial hypertension-associated indicators at 3 months after treatment and the alterations in the levels of cardiac function-associated biochemical indicator brain natriuretic peptide (BNP), inflammatory factor tumor necrosis factor alpha (TNF-alpha), and mean pulmonary arterial pressure during treatment were compared between the 2 groups. RESULTS At 3 months after treatment, the pulmonary arterial hypertension-associated indicators human urotensin II and calcitonin gene-related peptide in the observation group were lower and higher, respectively, than those in control group. Moreover, the observation group had significantly lower BNP and TNF-alpha levels and mean pulmonary arterial pressure than the control group. After intervention, the echocardiographic parameters left ventricular ejection fraction (LVEF), cardiac output (CO), and stroke volume (SV) in both groups were significantly higher than those before intervention, and the observation group had significantly higher LVEF, SV, and CO than the control group after intervention. CONCLUSIONS Beraprost sodium combined with sildenafil for left heart failure complicated with pulmonary arterial hypertension can effectively improve pulmonary arterial hypertension, alleviate left heart failure, and reduce inflammatory responses, thereby achieving better clinical efficacy in patients.


MicroRNA-490-5p is a novel tumor suppressor targeting c-FOS in human bladder cancer.
Recent studies have demonstrated the critical roles of micro-RNAs in tumorigenesis and tumor progression. Here, we describe the regulation and function of miR-490-5p in bladder cancer. Paired tissue samples were collected from bladder cancer patients (n = 20). Real-time PCR revealed that miR-490-5p expression was significantly down-regulated in human bladder cancer tissues and cells. Also there was an inverse relationship between the expression level of miR-490-5p and the pathological grade of bladder cancer. Western blotting was performed to detect the expression levels of c-FOS and TET1 in 6 matched tumor tissue samples and 4 bladder cell lines. Furthermore, to better understand the underlying mechanisms of miR-490-5p, we conducted gain and loss of function analysis by transfecting bladder cancer T24 cells with chemically synthesized miR-490-5p mimics and inhibitor, respectively. We found that overexpression of miR-490-5p in T24 cells could inhibit cell proliferation and invasion and induce cell apoptosis. Conversely, suppression of miR-490-5p expression induced cell proliferation and invasion, while it inhibited cell apoptosis. In addition, our bioinformatics prediction and experimental data showed that c-FOS was a potential target of miR-490-5p. The expression level of c-FOS was significantly decreased after miR-490-5p overexpression and significantly increased after miR-490-5p suppression, indicating that c-FOS was a target of miR-490-5p. These findings suggest that miR-490-5p is a novel tumor suppressor, contributing to the carcinogenesis of bladder cancer by targeting c-FOS.


Results from a First-in-Human Trial of a Novel Vascular Sealant.
Suture hole bleeding from synthetic grafts presents a hemostatic challenge. The designs of many vascular sealants are not optimal (non-adherence to wet surfaces, excessive swelling, inflexible). PreveLeak™ (formerly ArterX ((®)) ) is a polyaldehyde-bovine serum albumin-based sealant whose efficacy, safety, and performance were evaluated in this first-in-human study. A prospective, single-arm, multicenter study was performed in patients undergoing open vascular reconstructions with prosthetic grafts. Sealant was applied to the suture line after completion of the anastomosis. The primary endpoint was the incidence of immediate sealing (without clinically significant bleeding) upon clamp release. Secondary endpoints were time to sealing, safety, and assessment of product performance. Fifty-six anastomoses were performed in 32 patients. Grafts were Dacron (66% of sites), polytetrafluoroethylene (PTFE; 32%), or both Dacron and PTFE (2%). The femoral artery was the most common site of anastomosis (41% of sites). Immediate sealing after clamp release was achieved at all anastomoses (100%); 93% had no bleeding and 7% had oozing. No rebleeding occurred during 10 min of observation. The three most common adverse events were graft or bypass occlusion (n = 5 patients), infection (n = 4), and seroma (n = 3); none were device related. The sealant was considered easy to apply, quickly forming a soft gel, and adhering to tissue and grafts. PreveLeak effectively sealed anastomotic suture lines during vascular reconstruction procedures and was considered easy to use. Adverse events were consistent with those commonly observed in patients undergoing surgical procedures. These results provided the support for conducting a larger controlled clinical trial.


Superparamagnetic hollow hybrid nanogels as a potential guidable vehicle system of stimuli-mediated MR imaging and multiple cancer therapeutics.
Hollow hybrid nanogels were prepared first by the coassembly of the citric acid-coated superparamagnetic iron oxide nanoparticles (SPIONs, 44 wt %) with the graft copolymer (56 wt %) comprising acrylic acid and 2-methacryloylethyl acrylate units as the backbone and poly(ethylene glycol) and poly(N-isopropylacrylamide) as the grafts in the aqueous phase of pH 3.0 in the hybrid vesicle structure, followed by in situ covalent stabilization via the photoinitiated polymerization of MEA residues within vesicles. The resultant hollow nanogels, though slightly swollen, satisfactorily retain their structural integrity while the medium pH is adjusted to 7.4. Confining SPION clusters to such a high level (44 wt %) within the pH-responsive thin gel layer remarkably enhances the transverse relaxivity (r2) and renders the MR imaging highly pH-tunable. For example, with the pH being adjusted from 4.0 to 7.4, the r2 value can be dramatically increased from 138.5 to 265.5 mM(-1) s(-1). The DOX-loaded hybrid nanogels also exhibit accelerated drug release in response to both pH reduction and temperature increase as a result of the substantial disruption of the interactions between drug molecules and copolymer components. With magnetic transport guidance toward the target and subsequent exposure to an alternating magnetic field, this DOX-loaded nanogel system possessing combined capabilities of hyperthermia and stimuli-triggered drug release showed superior in vitro cytotoxicity against HeLa cells as compared to the case with only free drug or hyperthermia alone. This work demonstrates that the hollow inorganic/organic hybrid nanogels hold great potential to serve as a multimodal theranostic vehicle functionalized with such desirable features as the guidable delivery of stimuli-mediated diagnostic imaging and hyperthermia/chemotherapies.


Temperate tree species show identical response in tree water deficit but different sensitivities in sap flow to summer soil drying.
Temperate forests are expected to be particularly vulnerable to drought and soil drying because they are not adapted to such conditions and perform best in mesic environments. Here we ask (i) how sensitively four common temperate tree species (Fagus sylvatica, Picea abies, Acer pseudoplatanus and Fraxinus excelsior) respond in their water relations to summer soil drying and seek to determine (ii) if species-specific responses to summer soil drying are related to the onset of declining water status across the four species. Throughout 2012 and 2013 we determined tree water deficit (TWD) as a proxy for tree water status from recorded stem radius changes and monitored sap flow rates with sensors on 16 mature trees studied in the field at Lägeren, Switzerland. All tree species responded equally in their relative maximum TWD to the onset of declining soil moisture. This implies that the water supply of all tree species was affected by declining soil moisture and that none of the four species was able to fully maintain its water status, e.g., by access to alternative water sources in the soil. In contrast we found strong and highly species-specific responses of sap flow to declining soil moisture with the strongest decline in P. abies (92%), followed by F. sylvatica (53%) and A. pseudoplatanus (48%). F. excelsior did not significantly reduce sap flow. We hypothesize the species-specific responses in sap flow to declining soil moisture that occur despite a simultaneous increase in relative TWD in all species reflect how fast these species approach critical levels of their water status, which is most likely influenced by species-specific traits determining the hydraulic properties of the species tree.


Protective Desmoplasia in Pancreatic Adenocarcinoma: High Vitamin D Receptor Expression and Collagen Content.
Vitamin D receptor (VDR) has been shown to suppress desmoplasia in pancreatic ductal adenocarcinoma (PDAC). Our aim was to assess the clinical effects of VDR expression and its correlation with collagen content in the desmoplasia of PDAC patients. This is a retrospective analysis of 127 patients with peritumoral desmoplasia resected for PDAC. VDR expression and collagen content were assessed by immunohistochemistry and correlated with clinical outcome. Patients were classified into those with high and those with low VDR expression. High VDR expression was associated with improved overall survival (OS) in localized disease (N0) (median= 33; 95%CI=26.4-39.6 vs. 18; 15.5-20.5 months, p=0.01). Patients with high vs. low collagen content had improved OS [34, (range=22.3-45.6 months) vs. 17, (range=14.4-19.6 months), p<0.001]. The number of VDR+ cells was the same for patients with either high or low collagen content. Protective desmoplasia is associated with increased VDR expression and collagen content.


Antifungal innate immunity in C. elegans: PKCdelta links G protein signaling and a conserved p38 MAPK cascade.
Like other multicellular organisms, the model nematode C. elegans responds to infection by inducing the expression of defense genes. Among the genes upregulated in response to a natural fungal pathogen is nlp-29, encoding an antimicrobial peptide. In a screen for mutants that fail to express nlp-29 following fungal infection, we isolated alleles of tpa-1, homologous to the mammalian protein kinase C (PKC) delta. Through epistasis analyses, we demonstrate that C. elegans PKC acts through the p38 MAPK pathway to regulate nlp-29. This involves G protein signaling and specific C-type phospholipases acting upstream of PKCdelta. Unexpectedly and unlike in mammals, tpa-1 does not act via D-type protein kinases, but another C. elegans PKC gene, pkc-3, functions nonredundantly with tpa-1 to control nlp-29 expression. Finally, the tribbles-like kinase nipi-3 acts upstream of PKCdelta in this antifungal immune signaling cascade. These findings greatly expand our understanding of the pathways involved in C. elegans innate immunity.


Exploring the role of the HNF-1αG319S polymorphism in β cell failure and youth-onset type 2 diabetes: Lessons from MODY and Hnf-1α-deficient animal models.
The prevalence of youth-onset type 2 diabetes (T2D) is rapidly increasing worldwide, disproportionately affecting Indigenous youth with Oji-Cree heritage from central Canada. Candidate gene screening has uncovered a novel and private polymorphism in the Oji-Cree population in the hepatocyte nuclear factor-1 alpha (HNF-1α) gene, where a highly conserved glycine residue at position 319 is changed to a serine (termed HNF-1αG319S or simply G319S). Oji-Cree youth who carry one or two copies of the "S-allele" present at diagnosis with less obesity, reduced indicators of insulin resistance, and lower plasma insulin levels at diagnosis, suggestive of a primary defect in the insulin-secreting β cells. Few studies on the impact of the HNF-1αG319S variant on β cell function have been performed to date; however, much can be learned from other clinical phenotypes of HNF-1α-deficiency, including HNF-1α mutations that cause maturity-onset diabetes of the young 3 (MODY3). In addition, evaluation of Hnf-1α-deficient murine models reveals that HNF-1α plays a central role in the regulation of insulin secretion by regulating the expression of key genes involved in β cell glucose-sensing, mitochondrial function, and the maintenance of the β cell phenotype in differentiated β cells. The overall goal of this minireview is to explore the impact of HNF-1α-deficiency on the β cell to better inform future research into the mechanisms of β cell dysfunction in Oji-Cree youth with T2D.


Isolation and characterization of secretions from the plant-parasitic nematode Globodera pallida.
Electrophoresis of secretions collected from Globodera pallida revealed a smeared region between 25 and 50 kDa, and a single band of < 20 kDa. The secretions were used to raise an antiserum (LW1). Immunoblotting of parasite homogenates with LW1 differentiated G. pallida from its sibling species G. rostochiensis and revealed differences between different populations of G. pallida and G. rostochiensis. Indirect immunofluorescence studies with LW1 indicated that at least some of the secretions were surface localized and that antibody binding to the nematode surface was periodate sensitive. Periodate sensitivity indicated that these differences could be due to glycosylation differences. Glycosylation differences were also detected by blotting nematode homogenates with the lectin wheat germ agglutinin (WGA), WGA was also able to differentiate between G. rostochiensis which gave 2 bands at 130 kDa and 110 kDa, and G. pallida which produced 2 bands present at 120 kDa and 110 kDa. Further localization studies using immunoelectron microscopy demonstrated that antibody binding could be seen to secretions found in the pump chamber of the metacorpal bulb at the base of the stylet. From further specimens it could be observed that the contents of the subventral glands were heavily labelled, indicating that the material seen in the metacorpal bulb had originated from the subventral glands.


Characterization and mast cell origin of a chymotrypsin-like proteinase isolated from intestines of mice infected with Trichinella spiralis.
A proteinase was purified by cation exchange and affinity chromatography from the small intestines of mice infected with Trichinella spiralis. The enzyme was highly soluble and was chymotrypsin-like in its substrate specificities and susceptibility to inhibitors. It had a MW of 26,000, as determined by SDS-PAGE electrophoresis. Antibodies raised against the proteinase were affinity purified and their specificity confirmed by Western blot analysis. When used to localize the enzyme immunohistochemically, they reacted with granules of mast cells in the epithelium and lamina propria of the parasitized small intestine. The antibodies also bound to mast cell granules in a number of other sites, including tracheal epithelium, gastric mucosa, skin and tongue. Affinity-purified antibodies raised against rat mast cell proteinase II (RMCPII) cross-reacted with the mouse mast cell proteinase on Western blots.


Modulating role of 'Saptarangi' (Casearia esculenta) on membrane bound ATPase in streptozotocin diabetic rats.
We have studied the activities of adenosine triphosphatase (Na+/K+ATPase, Mg2+ATPase, Ca2+ATPase and Total ATPase) in erythrocyte, liver, kidney and cardiac tissues of control and Casearia esculenta treated streptozotocin (STZ) diabetic rats. The activity of Na+/K+ATPase plays a central role in the regulation of intra and extra cellular homeostasis and alteration of this transport system is thought to be linked to several complications of diabetes mellitus. An Mg2+ dependent ATPase activity is responsible for controlling the energy requiring process in cells whereas Ca2+ATPase is responsible for the signal transduction pathways and membrane fluidity. Activities of these enzymes were significantly altered (p < 0.05) in STZ diabetic rats. Oral administration of C. esculenta root extract for a period of 45 days resulted in significant (p < 0.05) reversal of these enzymes' activities to near normal. Thus the results suggest that C. esculenta protects the membrane integrity and functional status in STZ diabetic rats.


Colloidal CuInS2 Quantum Dots as Inorganic Hole-Transporting Material in Perovskite Solar Cells.
To develop novel hole-transporting materials (HTMs) is an important issue of perovskite solar cells (PSCs), especially favoring the stability improvement and the cost reduction. Herein, we use ternary quantum dots (QDs) as HTM in mesoporous TiO2/CH3NH3PbI3/HTM/Au solar cell, and modify the surface of CuInS2 QDs by cation exchange to improve the carrier transport. The device efficiency using CuInS2 QDs with a ZnS shell layer as HTM is 8.38% under AM 1.5, 100 mW cm(-2). The electrochemical impedance spectroscopy suggested that the significantly enhanced performance is mainly attributed to the reduced charge recombination between TiO2 and HTM. It paves a new pathway for the future development of cheap inorganic HTMs for the high efficiency PSCs.


Reversal of human immunodeficiency virus type 1-associated hematosuppression by effective antiretroviral therapy.
The immunodeficiency of human immunodeficiency virus type 1 (HIV-1) disease may be due to accelerated destruction of mature CD4+ T cells and/or impaired differentiation of progenitors of CD4+ T cells. HIV-1 infection may also inhibit the production of other hematopoietic lineages, by directly or indirectly suppressing the maturation of multilineage and/or lineage-restricted hematopoietic progenitor cells. To test this hypothesis, the effects of durable viral suppression on multilineage hematopoiesis in 66 HIV-1-seropositive patients were evaluated. Administration of effective antiretroviral therapy resulted in an increase in circulating CD4+ T cell counts and statistically significant increases in circulating levels of other hematopoietic lineages, including total white blood cells, lymphocytes, polymorphonuclear leukocytes, and platelets. These results suggest that a significant lesion in untreated HIV-1 disease may lie at the level of cell production from hematopoietic progenitors.


Endoscopic submucosal dissection of gastric tumors: A systematic review and meta-analysis.
To systematically review the medical literature in order to evaluate the safety and efficacy of gastric endoscopic submucosal dissection (ESD). We performed a comprehensive literature search of MEDLINE, Ovid, CINAHL, and Cochrane for studies reporting on the clinical efficacy and safety profile of gastric ESD. Twenty-nine thousand five hundred and six tumors in 27155 patients (31% female) who underwent gastric ESD between 1999 and 2014 were included in this study. R0 resection rate was 90% (95%CI: 87%-92%) with significant between-study heterogeneity (P < 0.001) which was partly explained by difference in region (P = 0.02) and sample size (P = 0.04). Endoscopic en bloc and curative resection rates were 94% (95%CI: 93%-96%) and 86% (95%CI: 83%-89%) respectively. The rate of immediate and delayed perforation rates were 2.7% (95%CI: 2.1%-3.3%) and 0.39% (95%CI: 0.06%-2.4%) respectively while rates of immediate and delayed major bleeding were 2.9% (95%CI: 1.3-6.6) and 3.6% (95%CI: 3.1%-4.3%). After an average follow-up of about 30 mo post-operative, the rate of tumor recurrence was 0.02% (95%CI: 0.001-1.4) among those with R0 resection and 7.7% (95%CI: 3.6%-16%) among those without R0 resection. Overall, irrespective of the resection status, recurrence rate was 0.75% (95%CI: 0.42%-1.3%). Our meta-analysis, the largest and most comprehensive assessment of gastric ESD till date, showed that gastric ESD is safe and effective for gastric tumors and warrants consideration as first line therapy when an expert operator is available.


Isolated Nocturnal Hypertension in Children.
Isolated nocturnal hypertension (INH) is attracting attention because it has been shown to correlate with target organ damage as well as cardiovascular events in adults. INH has also been reported in children especially in those with underlying diseases including chronic kidney disease and some studies reported association with markers of early target organ damage. INH occupies the majority of nocturnal hypertension. On the other hand, masked hypertension is largely attributed to INH. INH is usually diagnosed by ambulatory blood pressure monitoring. Recently, it became possible to monitor sleep blood pressure by an automated home blood pressure device feasible also in children. The epidemiology, methodology and reproducibility, pathophysiology, relation to target organ damage, and treatment of INH in children will be reviewed here along with adult data.


Antidepressants and Circadian Rhythm: Exploring Their Bidirectional Interaction for the Treatment of Depression.
Scientific evidence that circadian rhythms affect pharmacokinetics and pharmacodynamics has highlighted the importance of drug dosing-time. Circadian oscillations alter drug absorption, distribution, metabolism, and excretion (ADME) as well as intracellular signaling systems, target molecules (e.g., receptors, transporters, and enzymes), and gene transcription. Although several antidepressant drugs are clinically available, less than 50% of depressed patients respond to first-line pharmacological treatments. Chronotherapeutic approaches to enhance the effectiveness of antidepressants are not completely known. Even so, experimental results found until this day suggest a positive influence of drug dosing-time on the efficacy of depression therapy. On the other hand, antidepressants have also demonstrated to modulate circadian rhythmicity and sleep-wake cycles. This review aims to evidence the potential of chronotherapy to improve the efficacy and/or safety of antidepressants. It includes pre-clinical and clinical studies that demonstrate the relevance of determining the most appropriate time of administration for antidepressant drugs. In parallel, their positive influence on the resynchronization of disrupted circadian rhythms is also herein discussed. It is expected that this review will promote the investigation of chronotherapy for the treatment of depression, contribute to a better understanding of the relationship between antidepressants and circadian rhythms, and consequently promote the development of new therapeutics.


Behavioral phenotyping of a transgenic Caenorhabditis elegans expressing neuronal amyloid-beta.
Alzheimer's disease (AD) is rapidly reaching epidemic proportions in the United States, currently affecting more than 5 million individuals and predicted to affect 14 million by 2050. Despite a general consensus that the amyloid-beta (Abeta) protein plays a significant role in disease progression, the underlying pathology of the disease is not entirely clear. Caenorhabditis elegans is a simple organism that has been used as a model for basic mechanistic studies on the underlying pathological processes involved in AD. Previous studies from our labs demonstrated that transgenic C. elegans with muscle specific expression of human Abeta undergo rapid paralysis, and worms with neuronal expression of Abeta show deficits in chemotaxis to volatile chemicals. In this study, we evaluate the effect of neuron specific expression of Abeta on multiple neuronally controlled behaviors in a transgenic C. elegans. These worms demonstrate deficits in odorant preference associative learning behavior, and the serotonin-controlled behaviors experience-dependent learning and egg laying. These newly identified learning-deficit behavioral phenotypes in the neuronal Abeta C. elegans suggest that the model may be used to elucidate underlying pathological events related to development of AD and for pharmaceutical intervention.


Linear IgA/IgG bullous dermatosis successfully treated with omalizumab: A case report.
Linear IgA/IgG bullous dermatosis (LAGBD) is a rare, autoimmune blistering skin disease. We report a case of LAGBD in a 70-year-old woman. All common treatments were discontinued due to side effects or lack of treatment response. The patient was successfully treated with omalizumab which cleared her lesions after three months.


Declining prevalence of psychiatric disorder in older former prisoners of war.
The aim of this study was to examine change in the prevalence of psychiatric disorders over a decade late in the lives of ex-prisoners of war (POWs) and nonprisoner veterans of World War II. In 1982-83 we drew a random sample of POWs and non-POWs living in Sydney, Australia. They were interviewed by a psychiatrist at that time and again 9 years later. They also completed self-rating anxiety and depression scales. Anxiety disorders were the most prevalent and declined by half from 32.7% at the first interview to 16.8% 9 years later (p < .001) whereas the prevalence of depressive disorders fell by two-thirds from 26.9% to 8.7% (p < .001). In POWs the prevalence of both anxiety and depression declined more markedly than in non-POWs. Consistent changes also occurred in scores on the self-rating anxiety and depression scales. The psychological impact of these POWs' tragic wartime experience had at last begun to dim after nearly 50 years.


Control of post-thoracotomy pain by transcutaneous electrical nerve stimulation: effect on serum cytokine levels, visual analogue scale, pulmonary function and medication.
Transcutaneous electrical nerve stimulation (TENS) has been used to control post-thoracotomy pain with contrasting results. We aimed to assess the efficacy of TENS on post-thoracotomy pain in relation of four criterion measurements as: (i) cytokines; (ii) pain; (iii) respiratory function and (iv) intake of narcotic medication. Between January 2008 and October 2010, 58 patients underwent standard posterolateral thoracotomy for resectable lung cancer. Fifty patients were enrolled in the present study and randomized in two groups: TENS group (25 patients) who received postoperatively TENS for 5 days and placebo group (25 patients) without TENS. In both groups (i) serum cytokines (IL-6, IL-10, TNF-α) were measured by ELISA before surgery and at 6, 12, 24, 48, 72, 96 and 120 postoperative hours (POHs); (ii) at the same POHs, the pain score was measured using visual analogue scale (VAS) ranging from 0 to 10 levels; (iii) respiratory function (FEV 1% and FVC % of predicted value) were valuated on 72, 96 and 120 POHs; (iv) the total intake of narcotic medication given during postoperative period of 5 days was recorded. Repeated measures of analysis of variance assess the difference between two study groups. A value of P < 0.05 was considered statistically significant. Of the 50 patients enrolled, two patients of TENS group and two patients of the placebo group were lost to follow-up. (i) Serum IL-6 (P = 0.001), IL-10 (P = 0.001) and TNF-α (P = 0.001) levels in TENS group were significantly lower than in the control group; (ii) VAS score in TENS group was significantly lower than in the control group (P < 0.001); (iii) recovery of FEV 1 (P = 0.02) and of FVC (P = 0.02) was statistically better in the TENS group than in control group; (iv) morphine requirement was lower in the TENS group with respect to placebo TENS (P = 0.004). After 48 POHs, no patient required supplementary dose of morphine. TENS group compared with placebo-group presented a significant reduction of non-opioid consumption (P = 0.002). TENS is a valuable strategy to alleviate post-thoracotomy pain with reduction of cytokine production and of analgesic consumption, and with positive effects on pulmonary ventilation function.


Detection of t(X;Y) in 2 XX males using fluorescent in situ hybridization.
Males with a 46,XX karyotype generally have Y chromosomal material translocated to the pseudoautosomal region of the X chromosome. We have delineated two such cases using two color fluorescent in situ hybridization with probes from the short arm (DYZ2), centromere (DYZ3), and long arm (DYZ1) of the Y chromosome and a centromeric probes for the X chromosome (DXZ1). Using these techniques, the two patients are identified as having the karyotype 46,X,der(X)t(X;Y) (p22;p11) and a phenotype consistant with this translocation. Azoospermia in these patients is explained by the absence of Y long arm material including the recently identified candidate gene family for spermatogenesis.


In vitro studies with the scrapie agent.
Persistent infection with the scrapie agent has been established in L cells. The agent was propagated in homogenates of the cell line designated L-S. The L-S cells showed slower growth rate and morphological changes like pycnosis of nuclei and vacuolization of their cytoplasm. Cytogenetic analysis revealed rearrangement of chromosomes in L-S cells. In the course of passaging the number of cells with the characteristic marker chromosome decreased. Along with this cells were found with deletion of one arm of the marker chromosome. In addition, 3 new marker chromosomes were detected in infected cells, suggesting the influence of the scrapie agent on cytogenetic processes in scrapie-carrier cultures. The infectious activity of nucleic acids isolated from L-S cells was determined in BALB/c mice inoculated with untreated, DNase-treated and pronase-treated nucleic acid preparations. A slightly decreased infectious activity has been noted after DNase and pronase treatments.


Evaluation of carotid atherosclerosis from the perspective of blood flow reflection.
Detection and prevention of atherosclerosis at an early stage is important for its prevention. The aim of this study was to propose a valid and highly reliable index for the evaluation of carotid atherosclerosis or carotid function. Images of carotid Doppler wave profiles were processed using an image processing software, and the relative fluctuation in blood flow was calculated from the luminance in one cardiac cycle. Frequency analysis was performed and up to 10 time components of basic frequency (f1) were indicated. The evaluation function alpha was estimated by calculating the ratio of the sum of components f3-f10 against the f1 + f2 components. Blood pressure of the finger was continuously measured using Finapress during passive postural change from the supine to the standing position, the baroreceptor function was evaluated by the frequency method, and the plaque score was measured by ultrasound tomography. The influence of factors such as arterial compliance, blood vessel resistance, and heart rate on this index was studied using electric circuit model simulation. The subjects were 33 patients (18 men, 15 women) who had various types of atherosclerotic disease and hypertension. The average age was 67.3 + 12.2 years. The results showed that index alpha had a strong negative correlation with age and plaque score, and a weak positive correlation with baroreceptor function. Simulation results supported the clinical result. We proposed a new index to evaluate carotid atherosclerosis without blood pressure measurement using the carotid Doppler method. It is a potential index for detecting atherosclerosis of local arteries such as the carotid.


Structural basis for the temperature-induced transition of D-amino acid oxidase from pig kidney revealed by molecular dynamic simulation and photo-induced electron transfer.
The structural basis for the temperature-induced transition in the D-amino acid oxidase (DAAO) monomer from pig kidney was studied by means of molecular dynamic simulations (MDS). The center to center (Rc) distances between the isoalloxazine ring (Iso) and all aromatic amino acids (Trp and Tyr) were calculated at 10 °C and 30 °C. Rc was shortest in Tyr224 (0.82 and 0.88 nm at 10 and 30 °C, respectively), and then in Tyr228. Hydrogen bonding (H-bond) formed between the Iso N1 and Gly315 N (peptide), between the Iso N3H and Leu51 O (peptide) and between the Iso N5 and Ala49 N (peptide) at 10 °C, whilst no H-bond was formed at the Iso N1 and Iso N3H at 30 °C. The H-bond of Iso O4 with Leu51 N (peptide) at 10 °C switched to that with Ala49 N (peptide) at 30 °C. The reported fluorescence lifetimes (228 and 182 ps at 10 and 30 °C, respectively) of DAAO were analyzed with Kakitani and Mataga (KM) ET theory. The calculated fluorescence lifetimes displayed an excellent agreement with the observed lifetimes. The ET rate was fastest from Tyr224 to the excited Iso (Iso*) at 10 °C and from Tyr314 at 30 °C, despite the fact that the Rc was shortest between Iso and Tyr224 at both temperatures. This was explained by the electrostatic energy in the protein. The differences in the observed fluorescence lifetimes at 10 and 30 °C were ascribed to the differences in electron affinity of the Iso* at both temperatures, in which the free energies of the electron affinity of Iso* at 10 and 30 °C were -8.69 eV and -8.51 eV respectively. The other physical quantities related to ET did not differ appreciably at both temperatures. The electron affinities at both temperatures were calculated with a semi-empirical molecular orbital method (MO) of PM6. Mean calculated electron affinities over 100 snapshots with 0.1 ps intervals were -7.69 eV at 10 °C and -7.59 eV at 30 °C. The difference in the calculated electron affinities, -0.11 eV, was close to the observed difference in the free energies, -0.18 eV. The present quantitative analysis predicts that the highest ET rate can occur from a donor with longer donor-acceptor distance, which was explained by differences in electrostatic energy.


Gastric IgG4-Related Autoimmune Fibrosclerosing Pseudotumour: A Novel Location.
We describe the first reported case of an IgG4-related autoimmune fibrosclerosing pseudotumour located in the stomach of a 75-year old woman presenting with weight loss and vomiting. A lesion was detected in the gastric body at endoscopy. Subsequent characterisation by CT was suggestive of a gastrointestinal stromal tumour. Following laparoscopic resection, the patient recovered uneventfully. Histological examination of the resected specimen revealed an IgG4-related fibrosclerosing pseudotumour, a novel location for this histopathological entity.


Cell Wall Metabolism in Ripening Fruit: I. CELL WALL CHANGES IN RIPENING ;BARTLETT' PEARS.
;Bartlett' pear (Pyrus communis) fruits were picked at the mature, green stage and ripened at 20 C. Fruits at different stages of ripeness (based on flesh firmness) were homogenized, and the sugar and uronic acid contents of cell wall and soluble polysaccharides were determined. Substantial amounts of galacturonic acid and arabinose were lost from the wall fraction as the fruit ripened. Most of this cell wall material was recovered, in an 80% (volume/volume) ethanol-insoluble form, from the soluble fraction of tissue homogenates. Structural analysis of ethanol-precipitable material indicates that it is an acidic (pectic) polymer-bearing side groups containing variously-linked arabinosyl residues.


Dysphagia among geriatric trauma patients: A population-based study.
To determine the significance of dysphagia on clinical outcomes of geriatric trauma patients. This is a retrospective population-based study of geriatric trauma patients 65 years and older utilizing the Florida Agency for Health Care Administration dataset from 2010 to 2019. Patients with pre-admission dysphagia were excluded. Multivariable regression was used to create statistical adjustments. Primary outcomes included mortality and the development of dysphagia. Secondary outcomes included length of stay and complications. Subgroup analyses included patients with dementia, patients who received transgastric feeding tubes (GFTs) or tracheostomies, and speech language therapy consultation. A total of 52,946 geriatric patients developed dysphagia after admission during a 9-year period out of 1,150,438 geriatric trauma admissions. In general, patients who developed dysphagia had increased mortality, length of stay, and complications. When adjusted for traumatic brain and cervical spine injuries, the addition of mechanical ventilation decreased the mortality odds. This was also observed in the subset of patients with dysphagia who had GFTs placed. Of the three primary risk factors for dysphagia investigated, mechanical ventilation was the most strongly associated with later development of dysphagia and mortality. The geriatric trauma population is vulnerable to dysphagia with a large number associated with traumatic brain injury, cervical spine injury, and polytraumatic injuries that lead to mechanical ventilation. Earlier intubation/mechanical ventilation in association with GFTs was found to be associated with decreased inpatient hospital mortality. Tracheostomy placement was shown to be an independent risk factor for the development of dysphagia. The utilization of speech language therapy was found to be inconsistently utilized.


Some like it toxic.
Humans are notorious for disturbing terrestrial ecosystems worldwide, especially those that are in close proximity to urban areas. This disturbance has involved the accumulation of various types of chemical pollutants, of either agricultural or industrial origins, in both soil and water ecosystems. Pollutants have sometimes included essential plant nutrients, such as phosphate and nitrate, which have piled up throughout the years in many ecosystems as a consequence of aggressive agricultural practices, and a number of toxic or trace metals, e.g. iron, nickel or zinc that are important at low levels for the fitness of living organisms, but otherwise toxic at high concentrations (Ker & Charest 2010; Audet & Charest 2008). In order to reduce the load of toxic elements, scientists have used the natural capacity of several plant species to sequestrate them from the soil and, ultimately, render them harmless. This process, called phytoremediation, is rather slow, as most plants take years to build up their biomass but has been shown to be 'boostable' under experimental conditions in the presence of a particular group of plant symbionts in the soil – the arbuscular mycorrhizal fungi (AMF) (Gohre & Paszkowski 2006). These latter organisms are now widely recognized as being very beneficial for purposes of phytoremediation, but their biodiversity in the most disturbed ecosystems is still virtually unknown. Are these fungi really abundant in heavily polluted soils, or are their communities shrunken down like those of other microorganisms in the presence of heavy pollution? In this issue of Molecular Ecology, the study by Hassan et al. (2011) provides answers to these specific questions by determining the extent of AMF biodiversity across several urbanized areas in the City of Montre´al.


[Women under the knife--another history of surgery].
During the 19th century, surgery developed from management of lesions mainly on the surface of the body to operative treatment within the body as well as, at the same time, from a handicraft to a scientific discipline based on pathological anatomy. In the 1860s, ovariectomy became the 'key operation' in supervening traditional boundaries. The increasing safety of surgical intervention soon led to unspecifically indicated operations on normal organs within the female abdomen, aiming at curing 'typically female mental abnormalities', i.e. a kind of psychosurgery. This is still occasionally found today. The operative management of normal situations has even increased in gynaecology (hysterectomy) and obstetrics (caesarean section) in the 1970s and 1980s. Traditional medical ethos has therefore not been able to prevent it. Another new field, plastic and aesthetic surgery, had its specific ethical problems, which were well recognised as early as 1900. Because of the relative frequency of goitres and their operative treatment, after 1883 women came to the fore of the concepts of internal secretion, organ transplantation, and physiological surgery. In view of cultural and gender history, socio-cultural factors have been at least as decisive as medico-scientific 'facts' for the frequency of some of the operations performed on women. These operations have, in turn, accelerated the progress in surgery and medicine in general.


The Alusti Test, a Functional Assessment Scale Applicable to the Geriatric Population.
Decreases in functional ability generate dependence, limiting people's quality of life. Assessment tools are needed to evaluate functional abilities of the older adults that can objectively and accurately assess any type of user. Such proper or adapted tools are not always available. The aim of this study was to demonstrate the usefulness and universal application of the Alusti Test, a functional assessment scale, in the older population and to evaluate the sensitivity to change of the Alusti Test short version (Alusti-S) in a psychogeriatric hospitalized population. Longitudinal study was conducted in a psychogeriatric clinic in Navarra, Spain. The study sample comprised 539 persons of 65 years and older hospitalized at a psychogeriatric clinic (mean age 82.8 ± 7.3 years). The sensitivity to change was assessed upon admission and discharge through the application of three tests: Barthel Index, Complete Alusti Test, and Alusti-S. We verified sensitivity to change, as illustrated by an improvement of 24.7%, 13.8%, and 16.0%, respectively. Due to the greater functional deterioration upon admission, the improvement margin in the three tests was higher in patients over 85 years of age and in women. We consider the Alusti Test an innovative functional assessment tool due to its simplicity, sensitivity, and suitability to universal application in psychogeriatric populations. Correlating recommended physical activity based on the functional ability of the person, based on the Alusti Test, is a pending task that could be of interest for the sake of efficient interventions.


Discovering antisense reagents by hybridization of RNA to oligonucleotide arrays.
Antisense reagents have the potential to modify gene expression by interacting with DNA or mRNA to down-regulate transcription or translation. There have been a number of successful demonstrations of antisense activity in vivo. However, a number of problems must be solved before the method's full potential can be realized. One problem is the need for the antisense agent to form a duplex with the target molecule. We have found that most regions of mRNAs are not open to duplex formation with oligonucleotides because the bases needed for Watson-Crick base pairing are involved in intramolecular pairing. Using arrays of oligonucleotides that are complementary to extensive regions of the mRNA target, we are able to find those antisense oligonucleotides which bind optimally. There is good correspondence between the ability of an oligonucleotide to bind to its target and its activity as an antisense agent in in vivo and in vitro tests. To understand more fully the rules governing the process of duplex formation between a native RNA and complementary oligonucleotides, we have studied the interactions between tRNAphe and a complete set of complementary dodecanucleotides. Only four of the set of 65 oligonucleotides interact strongly. The four corresponding regions in the tRNA share structural features. However, other regions with similar features do not form a duplex. It is clear that ab initio prediction of patterns of interaction require much greater knowledge of the process of duplex formation than is presently available.


Discovery of Potent PROTACs Targeting EGFR Mutants through the Optimization of Covalent EGFR Ligands.
Drug resistance caused by epidermal growth factor receptor (EGFR) mutation has largely limited the clinical use of EGFR tyrosine kinase inhibitors (EGFR-TKIs) for the treatment of non-small-cell lung cancer (NSCLC). Herein, to overcome the intractable problem of drug resistance, proteolysis targeting chimeras (PROTACs) targeting EGFR mutants were developed by optimizing covalent EGFR ligands. Covalent or reversible covalent pyrimidine- or purine-containing PROTACs were designed, synthesized, and evaluated. As a consequence, covalent PROTAC CP17, with a novel purine-containing EGFR ligand, was discovered as a highly potent degrader against EGFRL858R/T790M and EGFRdel19, reaching the lowest DC50 values among all reported EGFR-targeting PROTACs. Furthermore, CP17 exhibited excellent cellular activity against the H1975 and HCC827 cell lines with high selectivity. Mechanism investigation indicated that the lysosome was involved in the degradation process. Importantly, the covalent binding strategy was proven to be an effective approach for the design of PROTACs targeting EGFRL858R/T790M, which laid the practical foundation for further development of potent EGFR-targeting PROTACs.


Nerve growth factor stimulation of p42/p44 mitogen-activated protein kinase in PC12 cells: role of G(i/o), G protein-coupled receptor kinase 2, beta-arrestin I, and endocytic processing.
In this study, we have shown that nerve growth factor (NGF)-dependent activation of the p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) pathway in PC12 cells can be partially blocked by pertussis toxin (which inactivates the G proteins G(i/o)). This suggests that the Trk A receptor may use a G protein-coupled receptor pathway to signal to p42/p44 MAPK. This was supported by data showing that the NGF-dependent activation of p42/p44 MAPK is potentiated in cells transfected with G protein-coupled receptor kinase 2 (GRK2) or beta-arrestin I. Moreover, GRK2 is constitutively bound with the Trk A receptor, whereas NGF stimulates the pertussis toxin-sensitive binding of beta-arrestin I to the TrkA receptor-GRK2 complex. Both GRK2 and beta-arrestin I are involved in clathrin-mediated endocytic signaling to p42/p44 MAPK. Indeed, inhibitors of clathrin-mediated endocytosis (e.g., monodansylcadaverine, concanavalin A, and hyperosmolar sucrose) reduced the NGF-dependent activation of p42/p44 MAPK. Finally, we have found that the G protein-coupled receptor-dependent component regulating p42/p44 MAPK is required for NGF-induced differentiation of PC12 cells. Thus, NGF-dependent inhibition of DNA synthesis was partially blocked by PD098059 (inhibitor of MAPK kinase-1 activation) and pertussis toxin. Our findings are the first to show that the Trk A receptor uses a classic G protein-coupled receptor-signaling pathway to promote differentiation of PC12 cells.


Hypoxemia due to inserting a bite block in severely handicapped patients.
In severely handicapped patients with severe cerebral palsy, stridor can be caused by a bite block in the mouth. So that dental treatment can be performed safely for these patients, the effect of a bite block on the respiratory function of 30 severely handicapped patients was investigated with two pulse oximeters. Of the 30 subjects examined, 96.7% showed SpO2 values above 95% in the resting state, and 26.7% showed SpO2 values under 94% after insertion of a small or middle-sized bite block. Patients who did not show SpO2 decrease while using a small bite block did have deterioration of SpO2 values when a middle-sized bite block was used. According to analysis by AIC, patients whose weight was less tha 20 kg, who were shorter than 130 cm, and who were more severely handicapped tended to have a deterioration of breathing function when using a bite block


Clinical significance of mitral leaflet flail.
There has been scant academic consideration paid to investigations of mitral leaflet flail in terms of clinical profile, surgical strategy, and surgical outcome. One hundred consecutive patients with mitral leaflet flail referred for surgical treatment in the past 4(2/3) years were included in this study. The most common reasons leading to mitral leaflet flail were chord rupture (38%), myxomatous degeneration (23%), and combined chord rupture and myxomatous degeneration (12%). Mitral leaflet flail was predominantly characterized by independent P(2) flail, followed by P(2,3) flail and independent A(2) flail. Chord rupture occurred in 54 patients, and the most commonly involved segments were P(2), P(2,3), and P(3). The most common risk factors for mitral valve replacement were papillary muscle rupture, extensive myxomatous degeneration, extensive chord rupture, and severely dilated mitral valve annulus. Multivariate regression analyses demonstrated that the development of mitral leaflet flail was significantly associated with the pertinent variables tested, especially correlated with insertion of the prosthetic ring, number of artificial chord, and presence of carotid stenosis. Mitral leaflet flail may affect patients of any age, but is more prevalent among males and younger patients. Mitral chord rupture was the leading cause for mitral leaflet flail. Myxomatous degeneration, infective endocarditis, mitral annulus calcification, and papillary muscle rupture were the next most common causes. An increased incidence of mitral leaflet flail was closely related to the chords of the posterior leaflet and the middle scallop. Due to the progressive disappointing prognosis of mitral leaflet flail, surgery should be performed at an early stage.


Parapharangeal edema: an uncommon complication of TMJ arthroscopy.
Ohnishi in 1975 first described temporomandibular joint (TMJ) arthroscopy. Along with its extensive use, a range of complications has emerged. We describe a patient who experienced parapharyngeal swelling after undergoing arthroscopy. Prolonged intubation up to 1 hour postoperatively was required. The swelling resolved completely over 6 h without further intervention.


Posttreatment attrition and its predictors, attrition bias, and treatment efficacy of the anxiety online programs.
Although relatively new, the field of e-mental health is becoming more popular with more attention given to researching its various aspects. However, there are many areas that still need further research, especially identifying attrition predictors at various phases of assessment and treatment delivery. The present study identified the predictors of posttreatment assessment completers based on 24 pre- and posttreatment demographic and personal variables and 1 treatment variable, their impact on attrition bias, and the efficacy of the 5 fully automated self-help anxiety treatment programs for generalized anxiety disorder (GAD), social anxiety disorder (SAD), panic disorder with or without agoraphobia (PD/A), obsessive-compulsive disorder (OCD), and posttraumatic stress disorder (PTSD). A complex algorithm was used to diagnose participants' mental disorders based on the criteria of the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition, Text Revision; DSM-IV-TR). Those who received a primary or secondary diagnosis of 1 of 5 anxiety disorders were offered an online 12-week disorder-specific treatment program. A total of 3199 individuals did not formally drop out of the 12-week treatment cycle, whereas 142 individuals formally dropped out. However, only 347 participants who completed their treatment cycle also completed the posttreatment assessment measures. Based on these measures, predictors of attrition were identified and attrition bias was examined. The efficacy of the 5 treatment programs was assessed based on anxiety-specific severity scores and 5 additional treatment outcome measures. On average, completers of posttreatment assessment measures were more likely to be seeking self-help online programs; have heard about the program from traditional media or from family and friends; were receiving mental health assistance; were more likely to learn best by reading, hearing and doing; had a lower pretreatment Kessler-6 total score; and were older in age. Predicted probabilities resulting from these attrition variables displayed no significant attrition bias using Heckman's method and thus allowing for the use of completer analysis. Six treatment outcome measures (Kessler-6 total score, number of diagnosed disorders, self-confidence in managing mental health issues, quality of life, and the corresponding pre- and posttreatment severity for each program-specific anxiety disorder and for major depressive episode) were used to assess the efficacy of the 5 anxiety treatment programs. Repeated measures MANOVA revealed a significant multivariate time effect for all treatment outcome measures for each treatment program. Follow-up repeated measures ANOVAs revealed significant improvements on all 6 treatment outcome measures for GAD and PTSD, 5 treatment outcome measures were significant for SAD and PD/A, and 4 treatment outcome measures were significant for OCD. Results identified predictors of posttreatment assessment completers and provided further support for the efficacy of self-help online treatment programs for the 5 anxiety disorders. Australian and New Zealand Clinical Trials Registry ACTRN121611000704998; http://www.anzctr.org.au/trial_view.aspx?ID=336143 (Archived by WebCite at http://www.webcitation.org/618r3wvOG).


An Integrated Regulatory Network Based on Comprehensive Analysis of mRNA Expression, Gene Methylation and Expression of Long Non-coding RNAs (lncRNAs) in Myelodysplastic Syndromes.
Myelodysplastic syndromes (MDS) are a heterogeneous group of disorders characterized by ineffective hematopoiesis, defective differentiation of hematopoietic precursors, and expansion of the abnormal clones. The prevalence of MDS has raised great concerns worldwide, but its pathogenetic mechanisms remain elusive. To provide insights on novel biomarkers for the diagnosis and therapy of MDS, we performed high-throughput genome-wide mRNA expression profiling, DNA methylation analysis, and long non-coding RNAs (lncRNA) analysis on bone marrows from four MDS patients and four age-matched healthy controls. We identified 1,937 differentially expressed genes (DEGs), 515 methylated genes, and 214 lncRNA that showed statistically significant differences. As the most significant module-related DEGs, TCL1A, PTGS2, and MME were revealed to be enriched in regulation of cell differentiation and cell death pathways. In addition, the GeneGo pathway maps identified by top DEGs were shown to converge on cancer, immunoregulation, apoptosis and regulation of actin cytoskeleton, most of which are known contributors in MDS etiology and pathogenesis. Notably, as potential biomarkers for diagnosis of MDS, four specific genes (ABAT, FADD, DAPP1, and SMPD3) were further subjected to detailed pathway analysis. Our integrative analysis on mRNA expression, gene methylation and lncRNAs profiling facilitates further understanding of the pathogenesis of MDS, and may promote the diagnosis and novel therapeutics for this disease.


Conjugation-Curtailing of Benzodithionopyran-Cored Molecular Acceptor Enables Efficient Air-Processed Small Molecule Solar Cells.
Small molecule solar cells (SMSCs) lag a long way behind polymer solar cells. A key limit is the less controllable morphology of small molecule materials, which can be aggravated when incorporating anisotropic nonfullerene acceptors. To fine-tune the blending morphology within SMSCs, a π-conjunction curtailing design is applied, which produces a efficient benzodithionopyran-cored molecular acceptor for nonfullerene SMSCs (NF-SMSCs). When blended with a molecular donor BDT3TR-SF to fabricate NF-SMSCs, the π-conjunction curtailed molecular acceptor NBDTP-M obtains an optimal power conversion efficiency (PCE) of up to 10.23%, which is much higher than that of NBDTTP-M of longer π-conjunction. It retains 93% of the PCE of devices fabricated in a glove box when all spin-coating and post-treating procedures are conducted in ambient air with relative humidity of 25%, which suggests the good air-processing capability of π-conjunction curtailed molecules. Detailed X-ray scattering investigations indicate that the BDT3TR-SF:NBDTP-M blend exhibits a blend morphology featuring fine interpenetrating networks with smaller domains and higher phase purity, which results in more efficient charge generation, more balanced charge transport, and less recombination compared to the low-performance BDT3TR-SF:NBDTTP-M blend. This work provides a guideline for molecular acceptors' design toward efficient, low-cost, air-processed NF-SMSCs.


Activation of a membrane-bound serine protease matriptase on the cell surface.
Matriptase is a type II transmembrane serine protease. The activation (i.e. conversion of the single-chain pro-form to the disulphide-linked-two-chain active form) of this enzyme is known to occur via a mechanism requiring its catalytic triad. We reported previously that the activated enzyme was produced in the conditioned medium when full-length rat matriptase was expressed in monkey kidney COS-1 cells. The present study aimed to address when and where the matriptase activation occurs. COS-1 cells expressing matriptase were labelled with a membrane-impermeable biotin derivative and then solubilized with Triton. Both activated and non-activated matriptase molecules were detected in the avidin precipitants of Triton extracts, whereas only the non-activated molecules were detected in the flow-through fraction of avidin-precipitation procedure. Single-chain matriptase has been thought to have an inherent activity. Indeed, a secreted single-chain variant of recombinant matriptase bearing mutation at the activation-cleavage site was found to exhibit the activity in hydrolyzing a synthetic peptide substrate at pH 7.5. However, the variant had little activity at pH 5.5, as found in the lumen of post-Golgi secretory vesicles. Altogether, it is concluded that the activation of matriptase may occur when the enzyme reaches the cell surface.