The morphology of a population of thoracic intersegmental interneurones in the locust.
A population of intersegmental interneurones with axons extending from the meso- to the metathoracic ganglion of the locust is described. They receive specific mechanosensory inputs from one mesothoracic leg. Their cell bodies are in group at the posterior of the mesothoracic ganglion, lying over the lateral base of each connective, and their primary neurites emerge in one of four bundles. Their mesothoracic branches are ipsilateral to the cell bodies and the leg from which they receive inputs. Each interneurone has two to six mesothoracic secondary neurites that divide and form a dense field of arborizations in specific regions of the neuropil so that each individual interneurone has a characteristic shape that is an elaboration of a basic and common plan. An interneurone excited by tibial campaniform sensilla and tarsal hair afferents branches in the intermediate neuropil and the ventral association center where the afferents from these receptors also project. An interneurone excited by proprioceptive inputs from the tarsus arborizes in the dorsal and intermediate neuropils, lateral to the ventral intermediate and ventral median tracts, in the same area as the proprioceptors afferents. An interneurone inhibited by proprioceptive inputs from the tibia (and wing) arborizes only in the dorsal neuropil, where there are no afferent projections. Some interneurones have one to three axonal branches with sparse and varicose side branches in the mesothoracic ganglion, which resemble the metathoracic axonal branches. The metathoracic axonal branches are mostly restricted to the dorsal neuropil and the dorsal part of the intermediate neuropil where local non-spiking interneurones and motor neurones controlling movements of the hind leg also project. The overlap between the branches of the sensory afferents and the intersegmental interneurones in the mesothoracic ganglion and between those of the nonspiking local interneurones or motor neurones and intersegmental interneurones in the metathoracic ganglion suggest that these interneurones are responsible for transferring information about the action of one leg to an adjacent leg.


Temperature-Induced Coloration and Interface Shell Cross-Linking for the Preparation of Polymer-Based Opal Films.
The formation of colloidal crystals and their use as photonic materials are of high interest for various technologies in the field of sensing applications, as templates, absorber materials, catalysts, and membranes. In this study, core-shell particles consisting of a cross-linked poly(methyl methacrylate) core featuring a (polyacrylonitrile-co-styrene) shell are synthesized by starved-feed emulsion polymerization. The resulting particles are investigated with respect to size and monodispersity, as well as the core-to-shell ratio, by means of dynamic light scattering and transmission electron microscopy. Optimized particle sizes are 218 nm for the cores and 276 nm for the core-shell particles. For the formation of highly ordered and free-standing opal films, the particles are processed by the melt-shear organization technique. The resulting films show angle-dependent reflection colors, while reflected colors can be tailored by the design of the core-shell particles. As a focus of this work, polyacrylonitrile as part of the copolymer particle shell is advantageously used both for particle opal film stabilization and for tailoring the reflection colors of the opal films. It is shown that the cyclization reactions at the interface of the particles and within the matrix material significantly influence the optical properties of the opal films upon thermal treatment at 240 °C and for different heat holding times. For instance, the change of color can be simply set from red to blue upon defined thermal treatment conditions. Via this convenient protocol, brilliant reflection colors can thus be obtained based on the insights into the structure-property relationships of the underlying particle architectures and interface reactions. The scalable opal films will pave the way to functional colored materials as interesting candidates for a manifold of sensing applications and temperature-responsive polymeric materials.


Neuroglial choristoma presenting as congenital lid tumor.
A 12-month-old boy presented with a diffuse solid tumor of the nasal portions of the lower lid, which had caused almost complete narrowing of the interpalpebral fissure since birth. Clinically, it was suspected to be a mesenchymal tumor. Radiological studies revealed no bony defects in the orbit. The computerized tomographic (CT) scan disclosed a porencephalic cyst in the ipsilateral cerebral hemisphere. Excisional biopsy of the lid tumor revealed ectopic neuroglial tissue. The immunocytochemical demonstration of glial fibrillary acidic protein (GFAP) was consistent with the electron microscopic findings that disclosed fibrillary astrocytes with an abundance of typical 9- to 10-nm glial filaments. Heterotopic neuroglial tissue should be part of the differential diagnosis of congenital lid tumors; its occurrence may be associated with other anomalies of cerebral organogenesis.


Mucinous metaplasia in the prostate gland.
The prostate gland normally secretes neutral mucosubstances that can be detected within the lumina of acini and ducts; adenocarcinomas often produce both acidic and neutral mucins, a feature that has been suggested to be of some diagnostic use. The presence of mucin-filled cells is not, however, a feature of the normal prostate. Over the last few years, we have observed tall, columnar, mucin-secreting cells in a variety of conditions in 12 benign prostates. All cases were stained histochemically for mucin with Mayers' mucicarmine, alcian blue (pH 2.7), and periodic-acid-Schiff with diastase digestion. In four cases, immunoperoxidase stains for prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) were performed. Mucin-secreting cells were found in the foci of sclerotic atrophy (n = 5), transitional cell metaplasia (n = 3), basal cell hyperplasia (n = 2), prostatrophic hyperplasia (n = 1), and nodular hyperplasia (n = 1). In all examples, the cells stained intensely with PAS, mucicarmine, and alcian blue. The cells were nonreactive for PSA and PAP in the cases studied. To our knowledge, the presence of tall, columnar, mucin-secreting cells has not been previously described in atrophy or basal cell hyperplasia. These observations expand our appreciation of the histologies that may be seen in the prostate gland; in addition, the recognition of acidic mucin-secreting cells in benign lesions points to the nonspecificity of this finding in the diagnosis of malignancy.


Nerve growth factor precursors in the rat thyroid and hippocampus.
A nerve growth factor (NGF) precursor form of about 24 kDa was identified in homogenates of rat thyroid and hippocampus by immunoprecipitation using three sera raised against a synthetic peptide that reproduces the sequence -71 to -46 of the proNGF molecule. Besides this species, a 31 kDa protein, as well as a cleavage product of 12 kDa were also immunoprecipitated in both tissues by one of these sera.


Impact of peptide permeation enhancer on tight junctions opening cellular mechanisms.
The myristoylated pentapeptide, L-R5, contains an amino acid sequence of the zeta inhibitory peptide (ZIP) portion (pseudosubstrate) of protein kinase C zeta (PKC ζ). As PKC ζ is involved in the modulation of epithelial tight junctions (TJs) through the phosphorylation of TJ proteins, L-R5 was suggested to interact with the enzyme resulting in the enhancement of paracellular permeability. This study shows that L-R5 does not bind to the enzyme but interacts directly with TJ proteins. We show here that the binding of PKC ζ to occludin and its successive phosphorylation is prevented by L-R5, which leads to TJ disruption and enhanced epithelial permeability. Although L-R5 did not show any in vitro cytotoxicity, a proteomics study revealed that L-R5 interferes with other regulatory pathways, e.g., apoptosis and immune response. We suggest that structural modification of the peptide may increase the specificity TJ protein-peptide interaction.


Calcium phosphate bone cement for treatment of distal radius fractures: a preliminary report.
Distal radius fractures in osteoporotic patients are often complicated with a residual deformity and a subsequent stiff and painful wrist. The aim of this study was to evaluate the usefulness of calcium phosphate bone cement (CPC95) in the treatment of these fractures. Seven Colles type fractures in seven patients (all female; average age, 58 years) were treated. After a closed reduction, the fractures were fixed either by percutaneous pinning or by external skeletal fixation. The CPC95 was then injected into the cancellous bone defect through a small dorsal incision. The functional and radiological results were evaluated for up to 1 year. All patients were graded as good or excellent within 3 months, and all were graded as excellent at the final follow-up. The average duration of immobilization was 3.5 weeks. The overall shortening of the radius was 2.3 mm. In one patient, CPC95 extruded into the extensor tendon sheath and was surgically removed. Injection of CPC95 is a promising augmentation of osteosynthesis for distal radius fractures, although a prospective control study is mandatory to prove the usefulness of this material. The equipment and surgical technique should be refined to avoid the extrusion of CPC95.


Simple and sensitive method for determination of metronidazole in human serum by high-performance liquid chromatography.
A simple and sensitive HPLC method for determination of metronidazole in human plasma has been developed. A step of freezing the protein precipitate allowed an efficient separation of aqueous and organic phases minimizing the noise level and improved therefore the limit of quantitation (10 ng ml(-1) using 1 ml of plasma sample). The separation of compounds was performed on a RP 18 column with acetonitrile-aqueous 0.01 M phosphate solution (15:85, v/v) as mobile phase. Detection was performed by UV absorbance at 318 nm. Metronidazole was well resolved from the plasma constituents and internal standard. An excellent linearity was observed between peak-height ratios plasma concentrations over a concentration range of 0.01 to 10 microg ml(-1). Within-day and between-day precision (expressed by relative standard deviation) and accuracy (mean error in per cent) did not exceed 4% between 1 and 10 microg ml(-1) and 8.3 and 7.2% respectively for the limit of quantitation. The method is suitable for bioavailability and pharmacokinetic studies in humans.


Minoxidil sulfate induced the increase in blood-brain tumor barrier permeability through ROS/RhoA/PI3K/PKB signaling pathway.
Adenosine 5'-triphosphate-sensitive potassium channel (KATP channel) activator, minoxidil sulfate (MS), can selectively increase the permeability of the blood-tumor barrier (BTB); however, the mechanism by which this occurs is still under investigation. Using a rat brain glioma (C6) model, we first examined the expression levels of occludin and claudin-5 at different time points after intracarotid infusion of MS (30 μg/kg/min) by western blotting. Compared to MS treatment for 0 min group, the protein expression levels of occludin and claudin-5 in brain tumor tissue of rats showed no changes within 1 h and began to decrease significantly after 2 h of MS infusion. Based on these findings, we then used an in vitro BTB model and selective inhibitors of diverse signaling pathways to investigate whether reactive oxygen species (ROS)/RhoA/PI3K/PKB pathway play a key role in the process of the increase of BTB permeability induced by MS. The inhibitor of ROS or RhoA or PI3K or PKB significantly attenuated the expression of tight junction (TJ) protein and the increase of the BTB permeability after 2 h of MS treatment. In addition, the significant increases in RhoA activity and PKB phosphorylation after MS administration were observed, which were partly inhibited by N-2-mercaptopropionyl glycine (MPG) or C3 exoenzyme or LY294002 pretreatment. The present study indicates that the activation of signaling cascades involving ROS/RhoA/PI3K/PKB in BTB was required for the increase of BTB permeability induced by MS. Taken together, all of these results suggested that MS might increase BTB permeability in a time-dependent manner by down-regulating TJ protein expression and this effect could be related to ROS/RhoA/PI3K/PKB signal pathway.


TouchStat v. 3.00: a new and improved Monte Carlo adjunct for the sequential touching task.
The sequential-touching procedure is employed by researchers studying nonlinguistic categorization in toddlers. TouchStat 3.00 is introduced in this article as an adjunct to the sequential-touching procedure, allowing researchers to compare children's actual touching behavior to what might be expected by chance. Advantages over the Thomas and Dahlin (2000) framework include ease of use, and fewer assumptive limitations. Improvements over TouchStat 1.00 include calculation of chance probabilities for multiple "special cases" and for immediate intercategory alternations. A new feature for calculating mean run length is also included.


Chylothorax After Heart Surgery in Children.
Chylothorax is a consequence of a thoracic duct injury that can occur during surgical procedures in patients with congenital heart disease. It is associated with high rates of morbimortality and increased use of clinical and hospital resources. The aim of this study was to evaluate the risk factors, distribution, manifestations, complications, and treatments for chylothorax in patients undergoing cardiac surgery in a tertiary pediatric hospital in southern Brazil. This is a retrospective, quantitative study, in which all medical records (n = 166) of patients with chylothorax after pediatric cardiac surgery between January 2014 and December of 2020 and a matched control group (n = 166) were analyzed. Over the study period, there was an increase in incidence of chylothorax from 4.5% in 2014 to 7.6% in 2020, a trend that has been reported in the literature. After multivariate analysis, the following were identified as risk factors for the diagnosis of chylothorax: genetic syndrome (OR 2.298); prolonged cardiopulmonary bypass time (greater than 120 min) (OR 2.410); fluid overload in the immediate postoperative period (OR 1.110); and SIRS (OR 2.527). Mortality was two times greater (p = 0.021) and there was a higher rate (34.4%) of infection (p < 0.001) in patients who developed chylothorax. In addition, a sensitivity analysis was performed comparing patients with low- and high-output chylothorax (> 20 mL/kg), which confirmed unfavorable outcomes for the latter group. Herein, we show that hemodynamic alterations were important factors for diagnosis. Understanding the risk factors, outcomes, and complications helps early identification and enables the reduction of morbidity and mortality.


Sulfamethoxazole degradation by UV-Fe3+ activated hydrogen sulfite.
Exploration of novel advanced oxidation systems with high efficiency toward radical generation is of significant importance due to the extensive and versatile application of reactive species in the wastewater treatment. Herein we report a simple UV-catalytic homogeneous advanced oxidation system (UV/Fe3+/hydrogen sulfite (BS)), which is capable of generating abundant radicals (e.g., SO3-, SO4-, SO5- and HO) in the aqueous environment. Sulfamethoxazole (SMX) degradation using this system was tested. Results indicated that SMX could be degraded effectively by UV/Fe3+/BS and sulfate radical (SO4-) and hydroxyl radical (HO•) were verified to be presented in this system and be contributive to SMX removal. The acidic pH (4.0) and a low BS/Fe3+ ratio (10:1) were suitable for SMX degradation. The presence of fulvic acid (FA) and HCO3- strongly inhibited the degradation of SMX, but obvious acceleration was observed in the presence of NO3- due to its contribution on additional radical generation by photosensitization. Based on the detected transformation products through LC-MS analysis, the degradation pathway of SMX by UV/Fe3+/BS was proposed including hydroxylation and bond cleavage.


The relations among animal abuse, psychological disorders, and crime: Implications for forensic assessment.
The confluence of developments in the assessment of animal abuse, the evolution of psychiatric nosology for the diagnosis of conduct disorder, legislative changes involving crimes against non-human animals, and the recent inclusion of crimes against animals in the FBI's National Incident-Based Reporting System, highlights the critical need for examining the forensic dimensions of animal abuse cases. We provide an overview of the research literature on these topics in the hope that forensic evaluators will have an evidence-based framework for assessing cases they encounter that include perpetration of violence against animals.


Targeting tumors with non-viral gene delivery systems.
Targeting therapeutic genes to tumors is an attractive concept in curing malignant diseases. Systemic gene delivery systems are needed for therapeutic applications in which the target cells are not directly accessible, and which can only be reached via the systemic route. Recent developments in the field of non-viral gene delivery have shown that, based on (poly)cationic carrier molecules, DNA can be efficiently targeted to tumors via the bloodstream. Tailor-made synthetic vectors can be used to achieve predominant gene expression in tumor tissue. Therapeutic concepts based, for example, on suicide genes or cytokines, showed encouraging results in preclinical and also in first clinical evaluations.


The Pre-Ablation Circulating Tumor-Associated Inflammatory Index Predicts the Prognosis of Patients with Liver Metastasis from Pancreatic Cancer.
Ablation serves as a common local treatment for liver metastases from pancreatic cancer (PCLM), but the correlation between the prognosis of PCLM and inflammatory cytokines has been rarely reported. This study aimed to establish a cytokine-based prognostic model for patients with PCLM who are receiving ablation. Serum samples from peripheral blood were collected from patients with PCLM before their first ablation. Cytokines were measured using Luminex chips and ELISA. Cox regression and least absolute shrinkage and selection operator regression were used to select prognostic factors for overall survival (OS). Area under the receiver operating characteristic curve (AUC) was applied to compare the ability to predict survival. The relationship between cytokines and clinical factors was evaluated and their prognostic value was compared. Six optimal predictors were selected, including IL-2, IL-7, HGF, IFN-γ, CA19-9 and CEA. The risk model based on these predictors was built and named circulating tumor-associated inflammatory index (CTII). The CTII (AUCs > 0.90) showed superior performance to systemic immune-inflammation index (SII, AUCs < 0.65) in OS. A circulating cytokine-based risk model for patients with PCLM before first ablation has been proposed and validated, which has demonstrated superior performance in predicting survival and has the potential to inform clinical treatment strategies.


Unrecognized esophageal fish bone impaction with delayed presentation of acute spastic central chest pain: A case report.
Esophageal chest pain is difficult to be identified, and the diagnosis requires a high index of clinical suspicion. Upon presentation, they are difficult to be differentiated from acute coronary syndrome (ACS) by symptomatology alone. We report a 71-year-old woman with multiple risk factors for coronary heart disease who presented with acute central spastic chest pain and was diagnosed as ACS in emergency department. Chest computed tomography revealed 1 radiopaque lesion over the upper-third of the esophagus. One fishbone with 3-pointed heads stuck in the esophagus was noted under esophagogastroscopic examination. The fishbone was extracted successfully via endoscopy under general anesthesia. The woman was discharged uneventfully after 3 days' hospitalization. This case illustrates that, even in emergency, clinicians should always keep in mind the possibility of esophageal foreign body impaction when confronted with frank central chest pain without associated gastrointestinal symptoms. This holds true even in the scenario of multiple cardiovascular risk factors and absence of ingestion history.


[Extent of the surgical intervention for the purpose of ovariectomy in breast cancer patients].
In laparotomy of breast cancer patients to the end of performing ovariectomy a careful revision of abdominal viscera should be included in the general plan of the treatment for the principal lesion. This measure allows the recognition both of secondary changes in abdominal organs due to mammary gland tumor and the changes not related with the principal lesion but necessitating some widening of the extent of surgery.


Skin advanced glycation end products as a screening tool of neuropathy in type 2 diabetes mellitus.
To examine the diagnostic utility of skin advanced glycation end products (AGEs) as screening tool of neuropathy in type 2 diabetes mellitus (T2DM). We included 132 participants (88 men) with a mean age of 64.57 years and median T2DM duration of 14.5 years. Skin AGEs were measured with AGE reader mu connect (Diagnoptics) on the dominant arm and were interpreted as normal vs. elevated. Distal sensorimotor polyneuropathy (DSPN) was diagnosed by the Neuropathy Disability Score. Cardiovascular autonomic neuropathy (CAN), sympathetic and parasympathetic nervous system impairment were diagnosed by cardiovascular autonomic reflex tests. For DSPN, AGEs yielded high sensitivity (82.8%) and NPV (80.4 %) with moderate specificity (55.4 %). For CAN, they yielded relatively high sensitivity (75.0 %) and NPV (74.5 %) with low specificity (48.7 %). For sympathetic nervous system impairment, AGEs yielded relatively high sensitivity (75.0 %) and high NPV (84.3 %) with low specificity (43.9 %). For parasympathetic nervous system impairment, they yielded high PPV (81.0 %) with moderately high sensitivity (66.7 %) and moderate specificity (55.9 %). In a simplified approach, skin AGEs may be used as a screening tool of DSPN and CAN (including sympathetic and parasympathetic nervous system impairment) in T2DM.


Spatial dependency of shoulder muscle demands in horizontal pushing and pulling.
Pushing and pulling account for nearly half of all manual material handling tasks. The purpose of this investigation was to develop a 3-D spatial muscle activity map for the right upper extremity during pushing and pulling tasks. Nineteen males performed 140 ramped directional hand exertions (70 push; 70 pull) at locations along three axes aligned with the anatomical planes. Electromyography (EMG) of 14 sites on the right upper extremity was recorded. Two directional 3-way repeated measures ANOVAs assessed the influence of hand position on EMG. Hand position and exertion direction influenced total and individual muscle demand. During pulling exertions, all three hand location parameters influenced total muscle activity (p < 0.001) and similarly in pushing exertions (p < 0.002), though less pronounced than in pulling. Data were used to create equations to predict the muscle activity of untested hand locations for novel work design scenarios.


Effects of estrogen on prolactin and tuberoinfundibular dopaminergic neurons.
Serum prolactin concentrations and dopamine turnover in the striatum and median eminence were studied in male rats after the administration of estradiol benzoate. The alpha-methyltyrosine-induced reduction of dopamine concentrations in these brain regions was used to evaluate relative rates of turnover. Steady state dopamine concentrations in the median eminence and striatum were not altered by 1, 3 or 5 days of estradiol treatment. However, 3 or 5 days of estradiol administration enhanced dopamine turnover in the median eminence but not in the striatum. Estradiol treatment failed to alter dopamine turnover in the median eminence of hypophysectomized rats. Estradiol increased serum prolactin concentrations at all of the times examined. Although alpha-methyltyrosine also increased serum prolactin, this increase was further enhanced in estradiol-treated rats. The increased prolactin response to alpha-methyltyrosine and increased dopamine turnover in the median eminence of estradiol-treated rats suggests that tuberoinfundibular dopaminergic neurons may be part of a hormonal-neuronal negative feedback loop which functions to regulate prolactin secretion.


Daily time spent indoors in German homes--baseline data for the assessment of indoor exposure of German occupants.
Comprehensive time-activity studies, for use as a basis for estimates of personal exposure, are not readily available in Germany. This analysis of time spent indoors at home is based on data from "Dampness and mould in homes" (2000/ 2001)--a study of about 12,000 persons living in 5530 randomly selected apartments and houses in Germany. The results show the mean times per day people in Germany spend in their homes, classified by gender, age group, building location, city size, region, building type, owner-occupier status, number of people at home, smoking and ventilation habits, moisture emission and ill health factors such as asthma, allergy and number of acute respiratory infections per year. The overall mean time spent at home, 15.7 h per, is in accordance with results from US-American (15.6 h/day) and Canadian (15.8 h/day) human activity surveys carried out in the nineties, as well as being consistent with the German Environmental Survey (1990/92) and a small German study in 1987.


Colorectal cancer after cholecystectomy: absence of risk increase within 11-14 years.
The importance of cholecystectomy as a risk factor for colorectal cancer was analyzed in an historical cohort study covering 16,773 cases during 11-14 years completed after operation. The observed number of colorectal cancers (130) was lower than the expected 153.5 [relative risk (RR) = 0.85]. For cancer of the colon, the observed number was 87, which was near the 91 expected (RR = 0.95). A significantly increased risk (p less than 0.05; RR = 2.86) was found for cancer of the colon only during the first year after cholecystectomy, and this was judged to be due to cancers present but overlooked at the time of cholecystectomy. The incidence of rectal cancer was significantly decreased (RR = 0.69; p less than 0.05), with 43 observed versus 62.4 expected cases. The distribution of right-sided versus left-sided cancers within the cohort did not differ significantly from that in the general population. Our results do not as yet support previous epidemiologic observations of an increased risk of colorectal cancer after cholecystectomy.


Development of controlled release inhalable polymeric microspheres for treatment of pulmonary hypertension.
Pulmonary hypertension (PAH) is a condition of the lungs characterised by an elevated arterial pressure and increased vascular resistance. Existing medications have to be administered frequently, resulting in non compliance by patients. Little work has been reported to date where microspheres have been developed to control the release of drug for treatment of pulmonary hypertension. To transcend this drawback, controlled release microspheres were formulated to minimise the number of doses required for treatment of PAH. Nifedipine and polyvinyl alcohol (PVA) were used as the model drug and release modifier respectively. Microspheres were developed by varying the PVA concentration using the spray drying technique. The formulated microspheres were characterised in terms of particle size, morphology, crystallinity, interaction between PVA and nifedipine via Fourier transformed infra-red spectroscopy (FTIR) and differential scanning calorimetry (DSC), in vitro release profile by employing the United States Pharmacopeia Apparatus type II and in vitro aerosolisation profile by using multi-stage liquid impinger (MSLI). The toxicity of PVA on lung epithelial cells was tested using human alveolar basal epithelium A549 cell line. From the data, it was observed that the microspheres were within the inhalable range (1-10 μm) with spherical morphology. The X-ray diffraction demonstrated that the microspheres were amorphous. There was no interaction between PVA and nifedipine during the formation of microspheres as seen by FTIR. The in vitro release profile showed a burst release followed by controlled release. A more prolonged release can be achieved by increasing the PVA:nifedipine ratio. In vitro aerosolisation showed that the Fine Particle Fractionemitted of the microspheres is greater than 20%, which is similar to that of marketed inhalation formulations. PVA was found to have insignificant effect on cell viability after 48 h of exposure to A549 cell line. In conclusion, microspheres of nifedipine and PVA, prepared by spray drying were found to exhibit suitable properties to achieve controlled release by the inhalation route.


Elton Mayo and Thomas Henry Reeve Mathewson: the forgotten Australian pioneers of the treatment of patients with shell shock, neurasthenia and nervous breakdown.
The contributions of Australians on shell shock are absent from the literature. However, two Australians were pioneers in the treatment of shell shock: George Elton Mayo (1880-1949) and Dr Thomas Henry Reeve Mathewson (1881-1975). They used psychoanalytic approaches to treat psychiatric patients and introduced the psychoanalytic treatment of people who suffered from shell shock. Their 'talking cure' was highly successful and challenged the view that shell shock only occurred in men who were malingering and/or lacking in fortitude. Their work demonstrated that people experiencing mental illness could be treated in the community at a time when they were routinely treated as inpatients. It also exemplified the substantial benefits of combining science with clinical knowledge and skill in psychology and psychiatry.


Temporal Analysis of Inflammatory Bowel Disease and Pancreatitis Co-Occurrence in Children and Adults in the United States.
Pancreatitis in inflammatory bowel disease has been attributed to peripancreatic intestinal disease and/or drug-induced pancreatic toxicity. We used large cohort analyses to define inflammatory bowel disease and pancreatitis temporal co-occurrence with a detailed descriptive analysis to gain greater insight into the pathophysiological relationship between these 2 diseases. Truven Health MarketScan private insurance claims from 141,017,841 patients (younger than 65 years) and 7,457,709 patients from 4 academic hospitals were analyzed. We calculated the prevalence of Crohn's disease or ulcerative colitis (UC) with acute pancreatitis or chronic pancreatitis (CP) and performed temporal and descriptive analyses. Of 516,724 patients with inflammatory bowel disease, 12,109 individuals (2.3%) had pancreatitis. Acute pancreatitis (AP) was 2-6x more prevalent than CP. In adults, AP occurred equally among Crohn's disease and UC (1.8%-2.2% vs 1.6%-2.1%, respectively), whereas in children, AP was more frequent in UC (2.3%-3.4% vs 1.5%-1.8%, respectively). The highest proportion of pancreatitis (21.7%-44.7%) was at/near the time of inflammatory bowel disease diagnosis. Of them, 22.1%-39.3% were on steroids during pancreatitis. Individuals with CP or recurrent pancreatitis hospitalizations had increased risk of a future inflammatory bowel disease diagnosis (odds ratio = 1.52 or 1.72, respectively). Pancreatitis in inflammatory bowel disease may not simply be a drug adverse event but may also involve local and/or systemic processes that negatively affect the pancreas. Our analysis of pancreatitis before, during, and after inflammatory bowel disease diagnosis suggests a bidirectional pathophysiologic relationship between inflammatory bowel disease and pancreatitis, with potentially more complexity than previously appreciated.


Temporal pattern discrimination within the receptive field of cat retinal ganglion cells.
ON-center and OFF-center receptive fields of cat retinal ganglion cells can be divided into two categories: sensitive (type N) and insensitive (type L) to three statistical temporal visual stimuli with different second order statistics but identical first order statistics (Tsukada et al. 1982). The temporal pattern sensitivity of type N response is closely related to the nonlinear stage of Y cells depending on the interaction between center and surround mechanism. The temporal pattern sensitivity of type N responses has a spatial profile within the receptive field; it is highly sensitive in the center region of the receptive field and less sensitive toward the field periphery. The temporal pattern sensitivity in the center region of the receptive field to statistical properties (irregular or regular) of a surrounding flash annulus shows modulation like a switching element: when the surrounding area is stimulated by a more regular flash stimulus with normal distribution of inter-stimulus intervals the system is sensitive (switching on) to the temporal pattern, while a change to an irregular one with an exponential distribution makes it insensitive (switching off) to the temporal pattern.


Monosodium glutamate induces cortical oxidative, apoptotic, and inflammatory challenges in rats: the potential neuroprotective role of apigenin.
Monosodium glutamate (MSG) is used as a flavor, and a taste enhancer was reported to evoke marked neuronal impairments. This study investigated the neuroprotective ability of flavonoid apigenin against neural damage in MSG-administered rats. Adult male rats were allocated into four groups: control, apigenin (20 mg/kg b.wt, orally), MSG (4 g/kg b.wt, orally), and apigenin + MSG at the aforementioned doses for 30 days. Regarding the levels of neurotransmitters, our results revealed that apigenin augmented the activity of acetylcholinesterase (AChE) markedly, and levels of brain monoamines (dopamine, norepinephrine, and serotonin) accompanied by lessening the activity of monoamine oxidase (MAO) as compared to MSG treatment. Moreover, apigenin counteracted the MSG-mediated oxidative stress by decreasing the malondialdehyde (MDA) levels together with elevating the glutathione (GSH) levels. In addition, pretreatment with apigenin induced notable increases in the activities of cortical superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR). Furthermore, apigenin attenuated the cortical inflammatory stress as indicated by lower levels of pro-inflammatory mediators such as interleukin-1 b (IL-1b), tumor necrosis factor-α (TNF-α), and nitric oxide (NO) as well as downregulated inducible nitric oxide synthase (iNOS) expression levels. Histopathological screening validated the abovementioned results and revealed that apigenin restored the distorted cytoarchitecture of the brain cortex. Thus, the present findings collectively suggest that apigenin exerted significant protection against MSG-induced neurotoxicity by enhancing the cellular antioxidant response and attenuating inflammatory machineries in the rat brain cortex.


Advances in Assessing Hazard and Risk to Emerging Threats and Emergency Response: Comparing and Contrasting Efforts of 3 Federal Agencies.
Federal statutes authorize several agencies to protect human populations from chemical emergencies and provide guidance to evacuate, clean, and reoccupy affected areas. Each of the authorized federal agencies has developed programs to provide managers, public health officials, and regulators, with a rapid assessment of potential hazards and risks associated with chemical emergencies. Emergency responses vary based on exposure scenarios, routes, temporal considerations, and the substance(s) present. Traditional chemical assessments and derivation of toxicity values are time-intensive, typically requiring large amounts of human epidemiological and experimental animal data. When a rapid assessment of health effects is needed, an integrated computational approach of augmenting extant toxicity data with in vitro (new alternative toxicity testing methods) data can provide a quick, evidence-based solution. In so doing, multiple streams of data can be used, including literature searches, hazard, dose-response, physicochemical, environmental fate, transport property data, in vitro cell bioactivity testing, and toxicogenomics. The field of toxicology is moving, towards increased use of this approach as it transforms from observational to predictive science. The challenge is to objectively and transparently derive toxicity values using this approach to protect human health and the environment. Presented here are examples and efforts toward rapid risk assessment that demonstrate unified, parallel, and complementary work to provide timely protection in times of chemical emergency.


Exosomes from MSCs overexpressing microRNA-223-3p attenuate cerebral ischemia through inhibiting microglial M1 polarization mediated inflammation.
To explore the therapeutic effect and possible mechanism of exosomes from MSCs overexpressing miR-223 on cerebral ischemia and microglia polarization mediated inflammation. Rats after middle cerebral artery occlusion and reperfusion (MCAO/R) surgery and microglia BV-2 exposed to oxygen and glucose deprivation (OGD) and cysteinyl leukotrienes (CysLTs) stimulation were subject to exosomes from miR-223-3p transfected MSCs treatment, respectively. Behavioral tests were applied to assess the rats' neurological function. FACS was used to analyze M1/M2 microglia BV-2. production of cytokines in the ischemic hemisphere and BV-2 was detected by ELISA or qRT-PCR. Western blotting and qRT-PCR were also used to examine the expression of cysteinyl leukotriene receptor 2 (CysLT2R) in vivo and in vitro. Exosomes from MSCs over expressing miR-223-3p decreased MCAO/R induced cerebral infarct volume, improved neurological deficits, promoted learning and memorizing abilities. They suppressed pro-inflammatory factors expression and promoted anti-inflammatory factors secretion in the ischemic cortex and hippocampus. In vitro, exosomal miR-223-3p exhibited a more evident impact on modulating mRNA expression and protein production of cytokines. It promoted M2 microglia transformation of M1 microglia induced by NMLTC4 with a concentration-dependent manner. Western blot and qRT-PCR also revealed exosomal miR-223-3p decreased mRNA and protein expression of CysLT2R in vitro and in vivo. Exosomal miR-223-3p from MSCs attenuated cerebral ischemia/reperfusion injury through inhibiting microglial M1 polarization mediated pro-inflammatory response, which may be related with inhibitory effect of exosomal miR-223-3p on CysLT2R.


Aging, immunity, and critical care nursing.
Age-related changes of the immune system along with underlying disease can reduce the elderly patients' chances of survival in critical care. Complications can be minimized when the health care team responds not only to the needs of the critically ill patient, but also to the needs specific to the elderly patient.


Changes in mental health literacy about depression: South Australia, 1998 to 2004.
To identify changes in mental health literacy in regard to depression between 1998 and 2004. Face-to-face interviews with a random and representative sample of the South Australian population in 2004, compared with a similarly conducted survey in 1998 that used the same vignette, questions and methodology. 3015 randomly selected participants, aged 15 years and over. Responses to both open-ended and direct questions about symptoms and treatment options for depression. The 3015 interviews conducted represented a response rate of 65.9%. Compared with 1998, in 2004 there was a significant increase in the proportion of people recognising depression in the vignette, acknowledging personal experience of depression, and perceiving professional assistance to be more helpful and less harmful. However, although more people nominated psychiatrists or psychologists as therapists of choice, the difference between 1998 and 2004 was not significant. There has been a significant increase in mental health literacy, at least as regards depression, in the South Australian community between 1998 and 2004. The lack of significant change in psychiatrists and/or psychologists being perceived as therapists of choice is of concern and suggests that community education about their expertise may be appropriate.


HLA analysis of immune checkpoint inhibitor-induced and idiopathic isolated ACTH deficiency.
Isolated adrenocorticotropic hormone deficiency is a rare disease; however, since immune check point inhibitors (ICIs) have become widely used, many more cases have been reported. In this study, we compared the human leukocyte antigen (HLA) signatures between ICI-induced isolated adrenocorticotropic hormone deficiency (IAD) and idiopathic IAD (IIAD). Clinical features and HLA frequencies were compared among 13 patients with ICI-induced IAD, 8 patients with IIAD, and healthy controls. HLA frequencies of healthy controls were adopted from a HLA database of Japanese population. Age and body mass index were higher, while the rate of weight loss was lower, in patients with ICI-induced IAD than in those with IIAD. No HLA alleles had a significantly higher frequency in patients with ICI-induced IAD than in healthy controls, whereas the frequencies of HLA-DRB1*09:01, HLA-DQA1*03:02, and DQB1*03:03 were significantly higher in patients with IIAD than in healthy controls. ICI-induced IAD and IIAD were different in terms of HLA frequencies. There were no specific HLAs related to ICI-induced IAD, whereas several HLAs in strong linkage disequilibrium were associated with IIAD. This might suggest that the two diseases have different pathological mechanisms. HLAs unique to IIAD may be helpful in predicting its pathophysiology.


Neoadjuvant treatment for resectable cancer of the esophagus and the gastroesophageal junction: a meta-analysis of randomized clinical trials.
There is no general agreement on the effect of neoadjuvant treatment for esophageal cancer on patient survival. A meta-analysis was performed to determine the effect of preoperative treatment on survival of patients with resectable esophageal cancer and the effect of preoperative treatment on patient mortality. A standard variance-based method was used to derive summary estimates of the absolute difference in both 2-year survival and treatment-related mortality. Eleven randomized trials involving 2311 patients were analyzed. Preoperative chemotherapy improved 2-year survival compared with surgery alone: the absolute difference was 4.4% (95% confidence interval [CI],.3%-8.5%). Marginal evidence of heterogeneity was eliminated by restricting attention to the four most recent studies, which increased the estimate to 6.3% (95% CI, 1.8%-10.7%). For combined chemoradiotherapy, the increase was 6.4% (nonsignificant; 95% CI, -1.2%-14.0%). Treatment-related mortality increased by 1.7% with neoadjuvant chemotherapy (95% CI, -.9%-4.3%) and by 3.4% with chemoradiotherapy (95% CI, -.1%-7.3%), compared with surgery alone. There seems to be a modest survival advantage for patients who receive neoadjuvant chemotherapy followed by surgery, as compared with surgery alone. There is an apparent increase in treatment-related mortality, mainly for patients who receive neoadjuvant chemoradiotherapy.


Effect of selenium on the organ distribution and binding of bismuth in rat tissues.
Subcutaneous administration of bismuth, both single and multiple, resulted in deposition of this metal mainly in the kidneys which contained over 50% of the 'accessible pool' of bismuth. In the kidneys bismuth was bound mainly by the soluble fraction in which it was complexed with a protein of molecular weight of about 7000. Multiple administration of bismuth increased the level of this protein. Selenite administration brought about an increase in the 'accessible pool' of bismuth, probably due to a drop in excretion, and also changes in the organ distribution of this metal. The retention in the kidneys was diminished while those in the liver and in other tissues were augmented. These changes were accompanied by a change in the chemical form of bismuth present in the kidneys manifested by the total disappearance of the protein complex of molecular weight of 7000. The increased synthesis of this protein due to bismuth administration was not abolished completely.


Third trimester cortisol is positively associated with gestational weight gain in pregnant women with class one obesity.
Prevalence of pre-pregnancy obesity and excessive gestational weight gain (GWG) are higher among women of color with low SES. Dysregulation of the Hypothalamic-Pituitary-Adrenal (HPA) axis and its end-product, cortisol, during pregnancy is hypothesized to be associated with excessive GWG. However, past studies have produced inconsistent findings and often did not include health disparities populations. This study examined the association between pre-pregnancy body mass index (BMI), third trimester diurnal cortisol, and GWG in low-income, predominantly Hispanic women. The MADRES study is an ongoing prospective cohort study of primarily Hispanic, low-income pregnant women and their children in Los Angeles, California. Data from 176 participants were included in this study. Total cortisol secretion (area under the curve, AUC) was quantified using four salivary cortisol samples (awakening, 30 min after awakening, afternoon, and bedtime) that were collected at home on one day during the third trimester of pregnancy. Moderation of the association between total cortisol and GWG by pre-pregnancy BMI was tested using multiple linear regression with a multiplicative interaction term. There was no association between total cortisol secretion and GWG overall (p = 0.82), but the association between total cortisol and GWG was stronger for women with class 1 pre-pregnancy obesity compared to women with normal pre-pregnancy BMI (interaction term p = 0.04). Results suggest that obesity status before pregnancy may be exacerbating the physiological impact of cortisol on GWG.


Activity of partially inhibited serine palmitoyltransferase is sufficient for normal sphingolipid metabolism and viability of HSN1 patient cells.
Hereditary sensory neuropathy type I (HSN1) is a common degenerative disorder of peripheral sensory neurons. HSN1 is caused by mutations in the gene, encoding the long chain base 1 of serine palmitoyltransferase (SPT) [Nat. Genet. 27 (2001) 309]. Here, we show a 44% reduction of SPT activity in transformed lymphocytes from HSN1 patients with mutation T399G in the SPTLC1 gene. However, the decrease in SPT activity had no effect on de novo sphingolipid biosynthesis, cellular sphingolipid content, cell proliferation and death (apoptosis and necrosis). The removal of extracellular sphingolipids did not affect viability of HSN1 cells. We also found no significant difference in whole blood counts, viability, and permeability to Triton X-100 of primary lymphocytes from HSN1 patients. These results suggest that, despite the inhibition of mutant allele, the activity of nonmutant allele of STP may be sufficient for adequate sphingolipid biosynthesis and cell viability. Therefore, the neurodegeneration in HSN1 is likely to be caused by subtler and rather long-term effect(s) of these mutations such as loss of a cell-type selective facet of sphingolipid metabolism and/or function, or perhaps accumulation of toxic species, including abnormal protein(s) as in other neurodegenerations.


Effect of exercise protocol and lead selection on the accuracy of heart rate-adjusted indices of ST-segment depression for detection of three-vessel coronary artery disease.
To assess the effect of exercise protocol and number of monitoring leads on the ability of the ST/HR slope and delta ST/HR index to identify three-vessel coronary artery disease, the exercise ECGs of 50 patients who had coronary arteriography were reviewed. Test performance of the ST/HR slope using the Cornell exercise protocol with 13 leads was compared with performance obtained from the standard 12 leads and from sets of only 3 leads, as well as with test outcome using Bruce protocol equivalent stages with multiple-lead sets. ST/HR slopes could be calculated in 100% of patients using data from the Cornell protocol, but in only 80% of patients using the Bruce protocol with 13 leads (chi 2 = 8.1, p less than 0.005) and 54% of patients using the Bruce protocol with 3 leads (chi 2 = 21.0, p less than 0.001). With the Cornell protocol and 13 leads, an ST/HR slope partition of 6.0 microV/bpm identified three-vessel disease with a sensitivity of 96%, specificity of 58%, and overall test accuracy of 76%. At matched specificity, the Bruce protocol 13-lead ST/HR slope partition of 5.0 microV/bpm had a sensitivity of only 48% and overall test accuracy of 53% for three-vessel disease in those patients with calculable test outcomes (each p less than 0.01). Receiver operating characteristic curve analysis confirmed the superior performance of data acquired with the Cornell protocol and demonstrated no significant loss of Cornell ST/HR slope performance calculated from fewer monitored leads. Performance of the delta ST/HR index was similar with 3 leads and with 13 leads.(ABSTRACT TRUNCATED AT 250 WORDS)


Seasonal changes in inhibitory currents in rat hippocampus.
Spontaneous inhibitory postsynaptic currents were recorded in voltage-clamped neurons (clamp potential -60 to -70 mV) in the pyramidal cell layer of the CA1 region of hippocampal slices from 3- to 4-month-old rats. The average time constant of decay of the currents progressively increased from March (early autumn) to July (mid-winter) and then declined progressively from July to November (late spring). The changes were statistically significant. It is suggested that such seasonal changes in the time course of inhibitory postsynaptic currents may have behavioural consequences and could explain the reported seasonal variations in the occurrence of disorders such as mania.


Synthesis and antimicrobial activity of amido linked pyrrolyl and pyrazolyl-oxazoles, thiazoles and imidazoles.
A new class of amido linked bis heterocycles viz., pyrrolyl/pyrazolyl-oxazoles, thiazoles and imidazoles were prepared by 1,3-dipolar cycloaddition of TosMIC and diazomethane to the respective cinnamamide derivatives and screened for antimicrobial activity. The chlorosubstituted imidazolyl cinnamamide (6c) is the most potential antimicrobial agent as it displayed strong antibacterial activity against Bacillus subtilis and antifungal activity against Penicillium chrysogenum.


Histopathological, immunohistochemical and special stain unraveling the enigmatic carcinosarcoma--A case report.
Carcinosarcoma is an extremely rare, highly malignant tumor having a characteristic of both epithelial and mesenchymal components; the epithelial component exhibiting focal squamous cell carcinoma and mesenchymal component having sarcomatoid stroma. The occurrence of carcinosarcoma in the oral cavity is very rare and only few cases have been reported in the literature, although its occurrence in other parts of the body has been widely reported.


Atractylodinol prevents pulmonary fibrosis through inhibiting TGF-β receptor 1 recycling by stabilizing vimentin.
Pirfenidone and nintedanib are only anti-pulmonary fibrosis (PF) drugs approved by the FDA. However, they are not target specific, and unable to modify the disease status. Therefore, it is still desirable to discover more effective agents against PF. Vimentin (VIM) plays key roles in tissue regeneration and wound healing, but its molecular mechanism remains unknown. In this work, we demonstrated that atractylodinol (ATD) significantly inhibits TGF-β1-induced epithelial-mesenchymal transition and fibroblast-to-myofibroblast transition in vitro. ATD also reduces bleomycin-induced lung injury and fibrosis in mice models. Mechanistically, ATD inhibited TGF-β receptor I recycling by binding to VIM (KD = 454 nM) and inducing the formation of filamentous aggregates. In conclusion, we proved that ATD (derived from Atractylodes lancea) modified PF by targeting VIM and inhibiting the TGF-β/Smad signaling pathway. Therefore, VIM is a druggable target and ATD is a proper drug candidate against PF. We prove a novel VIM function that TGF-β receptor I recycling. These findings paved the way to develop new targeted therapeutics against PF.


Echinococcus granulosus equinus: an ultrastructural study of the laminated layer, including changes on incubating cysts in various media.
The microfibrillate component of the laminated layer of Echinococcus granulosus equinus contains, except for the zone adjacent to the germinal layer, aggregates of electron-dense bodies displaying a sub-structure of electron-lucent spheres. The tegumentary syncytial cytoplasm contains randomly distributed electron-dense granules, many occurring near the apical plasmalemma, although exocytosis was rarely seen. Granules, similar in size and sub-structure to the bodies of the aggregates, also occur in the internuncial connexions and tegumentary cytons, suggesting that they may be produced in the cytons and released into the laminated layer via the internuncial connexions and tegumentary cytoplasm. Cysts incubated for 0.5-2.5 h in serum- and non-serum-containing media showed differences from non-incubated cysts. The distal half of the syncytium contained a progressive increase in the number of granules (distal: proximal 1.9:1 at 2.5 h; cf. 1:1 in non-incubated cysts), and exocytosis of granules into the laminated layer adjacent to the cyst had occurred. This cannot be attributed wholly to serum proteins. Cysts incubated for 21 h appeared 'normal', suggesting re-establishment of an equilibrium. Since the matrix of the laminated layer is considered homologous to the glycocalyx of other cestodes, the possible protective role played by the granules/bodies, characteristic of Echinococcus spp., is discussed.


A new modality in targeted delivery of epirubicin for tumor theranosis based on PEGylated silver nanoparticles: Design, radiolabeling and bioevaluation.
This work highlights boosting the tumor targeting efficiency of epirubicin through loading on a new radionanosystem, based on the effective role of silver nanoparticles (AgNPs). Accordingly, PEGylated silver nanoparticles (PEG/AgNPs) were prepared in a size of 20.2 ± 0.1 nm. Additionally, epirubicin was loaded on PEG/AgNPs with a loading efficiency of 63 ± 3 %. Furthermore, both of PEG/AgNPs and EPI/PEG/AgNPs were radiolabeled with 131I isotope with radiolabeling yields of 85 ± 0.2 % and 90.3 ± 1 %, respectively. The in-vivo distribution of 131I-PEG/AgNPs and 131I-EPI/PEG/AgNPs were examined in healthy and tumor bearing mice models. Excitingly, 131I-EPI/PEG/AgNPs revealed a reticuloendothelial system (RES) avoidance and prolonged circulating time. In addition, 131I-EPI/PEG/AgNPs showed fast targeting of tumor site by 25.1 ± 0.1 %ID/g within 0.5 h after intravenous injection. Subsequently, the outcomes provided 131I-EPI/PEG/AgNPs as a new potential system for enhancement of tumor targeting and theranosis (therapy and/or imaging).


Risk of recurrent ischemic stroke in patients with patent foramen ovale: The role of D-dimer.
Paradoxical embolism under elevated thromboembolic conditions is known to be the primary mechanism of patent foramen ovale (PFO)-related stroke. We hypothesized that higher levels of D-dimer, a marker of thromboembolism, could increase the risk of stroke recurrence in patients with PFO. We conducted a retrospective analysis of data from 1226 consecutive patients with acute ischemic cryptogenic stroke (CS) who underwent transesophageal echocardiography (TEE). D-dimer was assessed during admission. We used a multivariate Cox proportional hazards model to evaluate the association of long-term outcomes between the presence of PFO and levels of D-dimer. Of the 1226 patients, the study included 461 who underwent TEE. Among them, 242 (52.5%) had PFOs. Among PFO patients, those with a D-dimer level >1.0 mg/L had a significantly higher risk of stroke recurrence compared to those with <0.5mg/L (adjusted hazard ratio (aHR) 4.04, 95% confidence interval [CI] 1.63-10.02). A pattern of increased risk of event with increasing D-dimer levels was observed (Ptrend=0.008). However, there was no significant difference in the risk of stroke recurrence at any D-dimer level compared to D-dimer level <0.5 mg/L among patients without PFO. In these patients, there was little evidence of increased risk with increasing D-dimer levels (Ptrend=0.570). This study demonstrated that the elevated D-dimer level increased the recurrence of stroke in CS patients with PFO, particularly showing a dose-dependent relationship between D-dimer levels and recurrence. However, no such effect was observed in patients without PFO. These findings provide valuable insights into the potential benefits of anticoagulation for strokes related to PFO.


Besifloxacin, a novel fluoroquinolone antimicrobial agent, exhibits potent inhibition of pro-inflammatory cytokines in human THP-1 monocytes.
This study was conducted to evaluate the anti-inflammatory effects of besifloxacin, a novel fluoroquinolone under clinical evaluation for treatment of ophthalmic infections. Cytokine expression in human THP-1 monocytes was stimulated by lipopolysaccharide (LPS), and Luminex technology was used to determine the effect of besifloxacin on LPS-induced cytokine expression. Moxifloxacin, a marketed fluoroquinolone used in ophthalmic infections, was used as the control. LPS induced measurable cytokine expression for 14 of the 16 cytokines assayed. Besifloxacin significantly inhibited LPS-stimulated cytokine production in a dose-dependent manner, with a comparable [granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-1beta, IL-8, interferon-inducible protein (IP-10), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha)] or better [granulocyte CSF (G-CSF), IL-1alpha, IL-1 receptor antagonist (IL-1ra) and IL-6] potency compared with moxifloxacin. A significant inhibitory effect of besifloxacin was observed at 0.1 mg/L for IL-1alpha, at 1 mg/L for G-CSF, IL-1ra and IL-6 and at 30 mg/L for GM-CSF, IL-12p40, IL-1beta, IL-8, IP-10, MCP-1 and MIP-1alpha. Besifloxacin acts as an anti-inflammatory agent in monocytes in vitro; this attribute may enhance its efficacy in ocular infections with an inflammatory component and warrants further investigation.


Thapsigargin blocks the induction of long-term potentiation in rat hippocampal slices.
Experiments were performed to investigate whether intact intracellular Ca2+ pools are necessary for long-term potentiation (LTP) in the CA1 region of rat hippocampal slices. Thapsigargin (1 microM), which depletes most intracellular Ca2+ pools by blocking ATP-dependent Ca2+ uptake into intracellular compartments, blocked the induction but not the expression of LTP. Thapsigargin had no effect on synaptic transmission or on responses mediated by N-methyl-D-aspartate (NMDA) receptor activation. These data suggest that Ca2+ release from intracellular stores is required for the induction of LTP.


Identification of the molecular basis for phosphorylase hypersensitivity in cultured diabetic cardiomyocytes.
The focus of this study was to identify the molecular basis for the hypersensitive response of glycogen phosphorylase activation to epinephrine stimulation in alloxan diabetic-derived cardiomyocytes. Cyclic AMP levels were found not to be significantly different between normal and diabetic-derived cells while cGMP concentrations were found consistently to be significantly lower in diabetic-derived cells than in normal cells. Treatment with cyclic GMP analogues did not affect phosphorylase activation by epinephrine in normal cardiomyocytes whereas, IBMX, a nonselective phosphodiesterase inhibitor, had a significant effect on basal and agonist-stimulated phosphorylase activity in both normal and diabetic-derived cardiomyocytes. Differences in the time course for the rate of decay of phosphorylase a from agonist-stimulated to basal levels were observed between normal and diabetic cells. After 3 h in primary culture, phosphorylase a activity returned to basal levels more quickly in normal than in diabetic-derived cells while after 24 h in culture, the time for phosphorylase a decay was not significantly different between normal and diabetic myocytes and was longer than the 3 h response. After 3 h response. After 3 h in primary culture, no significant difference in phosphorylase kinase activity was observed between normal and diabetic-derived cells exposed to epinephrine whereas, after 24 h in culture, phosphorylase kinase activity was significantly decreased in diabetic cells under basal and agonist-stimulation conditions.(ABSTRACT TRUNCATED AT 250 WORDS)


Development of a patient decision aid prototype for adults with obstructive sleep apnea.
To describe the development and assess the usability of a patient decision aid (PtDA) prototype designed for newly diagnosed, treatment-naïve, obstructive sleep apnea (OSA) patients. A web-based PtDA was developed which focuses on two first-line treatment options: continuous positive airway pressure (CPAP) and mandibular advancement splints (MAS). Development was guided by the International Patient Decision Aid Standards (IPDAS). Usability was assessed in individuals at high risk for OSA based on the STOP-Bang questionnaire, the patient acceptance of decision aid, the System Usability Scale (SUS), and content analysis of open-ended user feedback. Eighty eligible participants completed the survey. The mean age was 54 years (SD = 8.9), 60 % of the sample was male, 78 % were university-educated, and 64 % were employed full-time. Participants took an average of 13.7 min (SD = 9.6) to complete the PtDA, with 39 participants choosing CPAP, 25 choosing MAS, and 16 choosing no treatment. The mean SUS score was 78.22 (SD = 15.13). The majority of individuals thought the PtDA was useful in making a decision (n = 77, 96 %) and would recommend it to others (n = 77, 96 %), while a third (n = 26, 33 %) thought it was slanted towards CPAP. The SUS indicated that the PtDA was acceptable and useful for participants. And useful for participants. User feedback has been used to improve the prototype, which will now undergo further testing in patients at the Vancouver Sleep Disorders Clinic.


Oral, esophageal and cutaneous lichen ruber planus controlled with alitretinoin: case report and review of the literature.
Therapy-resistant lichen planus (LP) can be a challenging condition for dermatologists. There are some case reports about successful treatments with alitretinoin of cutaneous and oral, but not of esophageal LP. We present the unique case of a patient with cutaneous, oral and esophageal LP which was refractory to classical treatment options (topical clobetasol propionate and pimecrolimus, intramuscular triamcinolone acetonide); because of systemic side effects the patient did not tolerate systemic acitretin dosed up to 25 mg daily. Oral alitretinoin was used at a dose of 30 mg daily. Both oral and skin changes as well as dysphagia completely resolved within 4 weeks without any severe side effects and the drug was used for 6 months. No papules, intraoral striae or dysphagia recurred during the 6 months of treatment. After 4 months the patient relapsed with mucosal patches so that a second cycle was initiated for 6 months where oral LP lesions resolved after 4 weeks also (with sporadic mild headache). Further studies are needed to better understand the impact of alitretinoin in LP. Our observation suggests alitretinoin as a new, well-tolerated treatment option for esophageal LP after failed response to conventional treatments.


Assessing lateral femoral condyle cartilage prior to medial UKA: MRI vs. Valgus stress radiograph.
The cartilage quality of the lateral compartment needs to be clarified prior to medial unicompartmental knee arthroplasty (UKA). Valgus stress radiograph has been recommended as the preferred tool. Some studies also show that magnetic resonance imaging (MRI) has a higher diagnostic value. So, we conducted this study to compare whether valgus stress radiographic lateral joint space width (LJSW) and MRI grading can accurately reflect cartilage quality and its screening value for UKA-suitable patients. One hundred and thirty eight knees proposed for UKA were enrolled prospectively. Valgus stress radiograph was taken to measure LJSW. LJSW > 4 mm was considered normal and suitable for UKA. For weight-bearing area cartilage of lateral femoral condyle, Recht grade was assessed by MRI preoperatively. Recht grades ≤ 2 were treated as non-high-grade injuries while Recht grades > 2 were treated as high-grade injuries. Outerbridge grade was the gold standard and was assessed intraoperatively. Patients with Outerbridge grades 0-2 (non-high-grade injuries) underwent UKA, and patients with Outerbridge grades 3-4 (high-grade injuries) underwent total knee arthroplasty (TKA). The diagnostic parameters of valgus stress radiograph and MRI for the selection of UKA candidates were calculated, and receiver operating characteristic curves were drawn. P < 0.05 was considered significant. Of 138 knees, 120 underwent UKAs, and 18 underwent TKAs. In terms of selecting UKA candidates, the sensitivity was close between MRI (95.0%) and valgus stress radiograph (96.7%), and the specificity, accuracy, positive predictive value and negative predictive value of MRI (94.4%, 94.9%, 99.1%, 73.9%, respectively) were higher than that of valgus stress radiograph (5.9%, 85.5%, 88.0%, 20.0%, respectively). The difference in area under the curve (AUC) between MRI (0.950) and LJSW (0.602) was significant (P = 0.001). Compared with valgus stress radiograph, MRI has excellent evaluation value in diagnosing lateral weight-bearing cartilage injuries and can be used as a reliable tool for selecting suitable UKA patients.


Analgesic effects of 3-carboxysalsolinol alone and in combination with morphine.
A biphasic dose-response pattern is generated by the isoquinoline, 3-carboxysalsolinol, in analgesia tests conducted in mice. Carbidopa pretreatment enhances this effect, as well as the morphine-induced analgesic increase by 3-carboxysalsolinol. Naloxone blockade of all of these responses suggests an interaction of the alcohol-based isoquinoline with central opiate receptors.


Pediatric soft tissue sarcomas.
Many of the soft tissue sarcomas that occur in children are of the same histology as those in adults; however, the relative prevalence of these sarcomas is different between children and adults. In some cases, the biologic behavior of pediatric sarcomas is more benign than that in adults. Treatment for sarcomas in children is also different. Pediatric sarcomas are more commonly responsive to chemotherapy. Furthermore, in children who are still growing, surgery and radiation are associated with higher morbidity than in adults. This article discusses the diagnosis and treatment of rhabdomyosarcoma and undifferentiated sarcomas, with an emphasis on surgical considerations, and the diagnosis and treatment of nonrhabdomyosarcomatous soft tissue sarcomas in children.


If you've employed one person with autism …: An individual difference approach to the autism advantage at work.
In this letter to the editor, we comment on the 'autism advantage' - the idea that superior skills associated with autism (e.g. attention to detail) present a talent in employment - an example of which is a recent discussion by Austin and Pisano. We welcome advocacy that raises awareness around the strengths and capabilities of people with autism, and also the need to reform human resource management processes that disadvantage them. However, we are concerned that, by highlighting certain stereotypes (e.g. the 'talented nerd lacking social graces'), the heterogeneity of autism may be overlooked and support needs downplayed. Furthermore, not appreciating individual differences might result in a misalignment between work-profile and employment, pressure to outperform peers without autism and a failure to appreciate the diverse interests of people with autism. We argue that an individual differences approach will prove more sustainable for improving long-term employment outcomes.


Oral cancer in a tobacco-chewing US population--no apparent increased incidence or mortality.
Smokeless tobacco use is an accepted risk factor for oral cancer in the United States, but the major proof of this is based largely on a single epidemiologic (case-control) comparison of women, whereas the chewing of tobacco is predominantly a habit of men. The present investigation sought to compare gender-specific oral cancer mortality and incidence rates in West Virginia, the state with the highest per capita consumption of smokeless tobacco, with rates from other states and with the US average rates. It was hypothesized that the cancer rates for West Virginia males would be significantly greater than the US average and greater than the rates for states with less smokeless tobacco consumption. Data from the West Virginia Cancer Registry for the years 1993 through 1995 were compared with data from contemporary Surveillance and Epidemiology End Results for the US (with respect to incidence) and from the Center for Disease Control and Prevention's National Center for Health Statistics (with respect to mortality). The average annual incidence rates (per 100,000 population) for oral/pharyngeal cancer in West Virginia males and females were 13.4 and 5.1, respectively; these compared with rates of 15.4 and 5.7 for the US. The average annual mortality rates (per 100,000 population) for the disease in West Virginia males and females were 4.2 and 1.6, respectively; these compared with 4.4 and 1.5 for the US. West Virginia oral/pharyngeal mortality rates for both genders were statistically significantly lower than US rates throughout the years 1950 through 1980. Among other potential oral cancer etiologic factors, the very low prevalence of alcohol abuse in West Virginia seemed to be relevant. The hypothesis was not confirmed by data analysis. West Virginia is the state with the highest per capita consumption of smokeless tobacco, yet it has less oral/pharyngeal cancer than the US average. The authors strongly urge additional and improved epidemiologic evaluation of the oral cancer risk of smokeless tobacco use in US males.


Separation of physiological factors influencing glucose-insulin kinetics in diabetic patients.
A new quantitative method was developed for separation of physiological factors influencing glucose intolerance in diabetes mellitus using a three-compartmental model and the intravenous glucose tolerance test (IVGTT) in humans. The present model includes the physiologic factors of the hepatic glucose balance function, the peripheral tissue's glucose utilization rate, and the insulin secretion rate. The insulin sensitivity parameter and hepatic glucose sensitivity parameter were estimated in optimal fitting of the model-based data of glucose and insulin concentrations to the measured IVGTT data in 9 normal and 11 diabetic subjects. The results show that these sensitivity parameters are important for separation of the effects of the interactive physiologic factors, and, also useful in evaluating different glucose-insulin kinetics in 3 clinical groups of normal and diabetic subjects.


Linking left hemispheric tissue preservation to fMRI language task activation in chronic stroke patients.
The preservation of near-typical function in distributed brain networks is associated with less severe deficits in chronic stroke patients. However, it remains unclear how task-evoked responses in networks that support complex cognitive functions such as semantic processing relate to the post-stroke brain anatomy. Here, we used recently developed methods for the analysis of multimodal MRI data to investigate the relationship between regional tissue concentration and functional MRI activation evoked during auditory semantic decisions in a sample of 43 chronic left hemispheric stroke patients and 43 age, handedness, and sex-matched controls. Our analyses revealed that closer-to-normal levels of tissue concentration in left temporo-parietal cortex and the underlying white matter correlated with the level of task-evoked activation in distributed regions associated with the semantic network. This association was not attributable to the effects of left hemispheric lesion or brain volumes, and similar results were obtained when using explicit lesion data. Left temporo-parietal tissue concentration and the associated task-evoked activations predicted patient performance on the in-scanner task, and also predicted patient performance on out-of-scanner naming and verbal fluency tasks. Exploratory analyses using the average HCP-842 tractography dataset revealed the presence of fronto-temporal, fronto-parietal, and temporo-parietal semantic network connections in the locations where tissue concentration was found to correlate with task-evoked activation in the semantic network. In summary, our results link the preservation of left posterior temporo-parietal structures with the preservation of task-evoked semantic network function in chronic left hemispheric stroke patients. Speculatively, this relationship may reflect the status of posterior temporo-parietal areas as cortical and white matter convergence zones that support coordinated processing in the distributed semantic network. Damage to these regions may contribute to atypical task-evoked responses during semantic processing in chronic stroke patients.


A novel guanidinium grafted poly(aryl ether sulfone) for high-performance hydroxide exchange membranes.
A novel poly(aryl ether sulfone) ionomer containing hexaalkylguanidinium groups was synthesized, and membranes formed from this polymer displayed large ionic clusters, high hydroxide conductivity, and excellent solubility in low boiling point water-soluble solvents such as ethanol and methanol.


Rapid automated superposition of shapes and macromolecular models using spherical harmonics.
A rapid algorithm to superimpose macromolecular models in Fourier space is proposed and implemented (SUPALM). The method uses a normalized integrated cross-term of the scattering amplitudes as a proximity measure between two three-dimensional objects. The reciprocal-space algorithm allows for direct matching of heterogeneous objects including high- and low-resolution models represented by atomic coordinates, beads or dummy residue chains as well as electron microscopy density maps and inhomogeneous multi-phase models (e.g. of protein-nucleic acid complexes). Using spherical harmonics for the computation of the amplitudes, the method is up to an order of magnitude faster than the real-space algorithm implemented in SUPCOMB by Kozin & Svergun [J. Appl. Cryst. (2001 ▸), 34, 33-41]. The utility of the new method is demonstrated in a number of test cases and compared with the results of SUPCOMB. The spherical harmonics algorithm is best suited for low-resolution shape models, e.g. those provided by solution scattering experiments, but also facilitates a rapid cross-validation against structural models obtained by other methods.


Comparison of peri-implant marginal bone level changes between tapered and straight implant designs: 5-year follow-up results.
The aim of this study was to compare straight and tapered implant designs in terms of marginal bone loss, the modified plaque index (mPI), and the modified bleeding index (mBI) for 5 years after functional loading. Twelve patients were recruited. Two types of implants were placed adjacent to each other: 1 straight implant and 1 tapered implant. Marginal bone loss, mPI, and mBI were measured every year for 5 years after loading. The straight implants showed 0.2±0.4 mm of marginal bone loss at 5 years after loading, while the tapered implants showed 0.2±0.3 mm of marginal bone loss; this difference was not statistically significant (P=0.833). Our analysis also showed no statistically significant differences in mPI (straight implants: 0.3±0.3 vs. tapered implants: 0.2±0.3; P=0.414) or in mBI (straight implants: 0.3±0.4 vs. tapered implants: 0.2±0.3; P=0.317) at 5 years after prosthesis delivery. Straight and tapered implants showed no significant differences with respect to marginal bone loss, mPI, and mBI for 5 years after loading.


Anti-solvent precipitation for the preparation of nobiletin nano-particles under ultrasonication-cis/reverse homogenization.
In order to address the issue of nobiletin's limited bioavailability, nobiletin nanoparticles (NNP) were created for the first time in this research employing an anti-solvent under ultrasonication-cis/reverse homogenization. Dimethyl sulfoxide (DMSO) was used as the solvent and deionized water as the anti-solvent to create the nobiletin solution. The optimal surfactant dose of surfactant dose of 0.43%; an ultrasonic period of 8.1 min, ultrasonic at a temperature of 64 °C and a solution concentration of 8.33 mg/mL, the method was optimized to obtain the minimum NNP diameter of 199.89 ± 0.02 nm. A dual optimization process of response surface PBD and BBD was used to minimize the size of HNP particles. Additionally, scanning electron microscopy revealed that the specific surface area of the NNP dramatically increased with the reduction of NNP particle size, and dissolving studies indicated the solubility and dissolution studies showed that NNP had substantially greater solubility and dissolution rates than raw nobiletin per unit time; as a result, the NNP produced by anti-solvent precipitation with a twofold homogenization system supported by ultrasound had a realistic potential for growth.


Mass fragmentographic analysis of monoamine metabolites in the spinal cord of rat after the administration of morphine.
A mass fragmentographic method was used in which homovanillic acid (HVA), methoxyhydroxyphenylglycol (MHPG), and 5-hydroxyindoleacetic acid (5-HIAA) were measured from a single sample. The results describe the effect of morphine on the metabolism of the major monoamines, dopamine (DA), noradrenaline (NA), and 5-hydroxytryptamine (5-HT) in the spinal cord. Morphine has very little effect on the metabolism of DA and NA in the spinal cord. However, morphine causes a significant increase in the metabolism of spinal 5-HT. The increase in 5-HIAA induced by morphine is not restricted to the dorsal horn. The three main functional regions of the cord--dorsal horn (sensory), zona intermedia (autonomic), and ventral horn (somatic motor)--are affected to the same degree. The results indicate that morphine causes a generalized activation of serotonin neurons in the spinal cord. There appears to be little or no selectivity for those serotonergic neurons that innervate the dorsal horn. The results are discussed with reference to current data, which indicate a fairly strong link between descending serotonergic nerves and the mechanism of action of morphine-induced analgesia.


Safety and immunogenicity of a variant-adapted SARS-CoV-2 recombinant protein vaccine with AS03 adjuvant as a booster in adults primed with authorized vaccines: a phase 3, parallel-group study.
In a parallel-group, international, phase 3 study (ClinicalTrials.govNCT04762680), we evaluated prototype (D614) and Beta (B.1.351) variant recombinant spike protein booster vaccines with AS03-adjuvant (CoV2 preS dTM-AS03). Adults, previously primed with mRNA (BNT162b2, mRNA-1273), adenovirus-vectored (Ad26.CoV2.S, ChAdOx1nCoV-19) or protein (CoV2 preS dTM-AS03 [monovalent D614; MV(D614)]) vaccines were enrolled between 29 July 2021 and 22 February 2022. Participants were stratified by age (18-55 and ≥ 56 years) and received one of the following CoV2 preS dTM-AS03 booster formulations: MV(D614) (n = 1285), MV(B.1.351) (n = 707) or bivalent D614 + B.1.351 (BiV; n = 625). Unvaccinated adults who tested negative on a SARS-CoV-2 rapid diagnostic test (control group, n = 479) received two primary doses, 21 days apart, of MV(D614). Anti-D614G and anti-B.1.351 antibodies were evaluated using validated pseudovirus (lentivirus) neutralization (PsVN) assay 14 days post-booster (day [D]15) in 18-55-year-old BNT162b2-primed participants and compared with those pre-booster (D1) and on D36 in 18-55-year-old controls (primary immunogenicity endpoints). PsVN titers to Omicron BA.1, BA.2 and BA.4/5 subvariants were also evaluated. Safety was evaluated over a 12-month follow-up period. Planned interim analyses are presented up to 14 days post-last vaccination for immunogenicity and over a median duration of 5 months for safety. All three boosters elicited robust anti-D614G or -B.1.351 PsVN responses for mRNA, adenovirus-vectored and protein vaccine-primed groups. Among BNT162b2-primed adults (18-55 years), geometric means of the individual post-booster versus pre-booster titer ratio (95% confidence interval [CI]) were: for MV (D614), 23.37 (18.58-29.38) (anti-D614G); for MV(B.1.351), 35.41 (26.71-46.95) (anti-B.1.351); and for BiV, 14.39 (11.39-18.28) (anti-D614G) and 34.18 (25.84-45.22 (anti-B.1.351). GMT ratios (98.3% CI) versus post-primary vaccination GMTs in controls, were: for MV(D614) booster, 2.16 (1.69; 2.75) [anti-D614G]; for MV(B.1.351), 1.96 (1.54; 2.50) [anti-B.1.351]; and for BiV, 2.34 (1.84; 2.96) [anti-D614G] and 1.39 (1.09; 1.77) [anti-B.1.351]. All booster formulations elicited cross-neutralizing antibodies against Omicron BA.2 (across priming vaccine subgroups), Omicron BA.1 (BNT162b2-primed participants) and Omicron BA.4/5 (BNT162b2-primed participants and MV D614-primed participants). Similar patterns in antibody responses were observed for participants aged ≥56 years. Reactogenicity tended to be transient and mild-to-moderate severity in all booster groups. No safety concerns were identified. CoV2 preS dTM-AS03 boosters demonstrated acceptable safety and elicited robust neutralizing antibodies against multiple variants, regardless of priming vaccine. Sanofi and Biomedical Advanced Research and Development Authority (BARDA).


Infant mouse brain passaged Dengue serotype 2 virus induces non-neurological disease with inflammatory spleen collapse in AG129 mice after splenic adaptation.
AG129 mice are known to be permissive to infection by multiple serotypes of Dengue virus (DENV). There exists a concern that mouse passaged strains of the virus may induce neurological complications rather than increased vascular permeability in these mice, hence the use of human clinical isolates of the virus to develop the AG129 mouse model of Dengue disease with increased vascular permeability. The present study evaluated four mouse brain passaged DENV strains, each belonging to a different serotype and three of them having an original isolation history in India, for their suitability to serve as candidates to induce rapid lethal disease in AG129 mice. While all the viruses were able to establish a productive infection in the spleen, none of them induced paralysis despite their mouse brain passage history. Only the type-2 virus acquired the ability to induce a lethal disease after a single round of spleen to spleen passage, and became highly virulent after five more rounds. This apparently non-neurological lethal disease was characterized by high viral burden, elevated vascular permeability, serum TNF-α surge immediately before moribund stage, transient leukocytosis followed by severe leukopenia, lymphopenia throughout the course of the infection, and transient thrombocytopenia. The disease was also characterized by inflammatory splenic collapse during moribund stage, reminiscent of spontaneous splenic rupture reported in rare cases of severe Dengue in humans.


Ginkgo diterpene lactones inhibit cerebral ischemia/reperfusion induced inflammatory response in astrocytes via TLR4/NF-κB pathway in rats.
Ginkgo biloba L. (Ginkgoaceae) is a traditional Chinese medicine known to treating stroke and other cardio-cerebrovascular diseases for thousands of years in China. Ginkgo diterpene lactones (GDL) attracted much attention because of their neuroprotective properties. To uncover the effects of GDL, which consist of ginkgolide A (GA), ginkgolide B (GB), and ginkgolide K (GK), on ischemic stroke, as well as the underlying molecular mechanisms. We used middle cerebral artery occlusion/reperfusion (MCAO/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) models mimicking the process of ischemia/reperfusion in vivo and in vitro, respectively. Anticoagulant effects of GDL were investigated on platelet activating factor (PAF), arachidonic acid (AA) and adenosine diphosphate (ADP)-induced platelet aggregation both in vivo and in vitro. We also evaluated the effects of GDL on lipopolysaccharide (LPS)-induced inflammatory response in primary cultured rats' astrocytes. Infarct size, neurological deficit score, and brain edema were measured at 72 h after MCAO. Immunohistochemistry was utilized to analyze neurons necrosis and astrocytes activation. Expression of pro-inflammatory cytokines, including tumor necrotic factor-α (TNF-α) and interleukin-1β (IL-1β) were detected using enzyme-linked immunosorbent assay (ELISA) and real time PCR. The levels of toll-like receptor 4 (TLR4) and nuclear factor κB (NF-κB) were assessed by real time PCR or Western blot. Compared with MCAO/R rats, GDL significantly reduced infarct size and brain edema, improved neurological deficit score. Meanwhile, GDL suppressed platelet aggregation, astrocytes activation, pro-inflammatory cytokines releasing, TLR4 mRNA expression and transfer of NF-κB from cytoplasm to nucleus. Furthermore, GDL alleviated OGD/R injury and LPS-induced inflammatory response in primary astrocytes, characterized by promoting cell viability, decreasing lactate dehydrogenase (LDH) activity, and inhibiting IL-1β and TNF-α releasing. In summary, GDL attenuate cerebral ischemic injury, inhibit platelet aggregation and astrocytes activation. The anti-inflammatory activity might be associated with the downregulation of TLR4/NF-κB signal pathway. Our present findings provide an innovative insight into the novel treatment of GDL in ischemic stroke therapy.


The Rosai-Dorfman Disease: A Differential Diagnosis in Cervical Swelling.
Rosai-Dorfman disease also known as sinus histiocytosis with massive lymphadenopathy is a rare benign disorder of unknown etiology. It is a benign condition which causes significant cervical lymphadenopathy in children and young adults. These cases are frequently misdiagnosed as lymphoma, and thus it is important to distinguish Rosai-Dorfman disease from other causes of neck swelling because of different treatment modalities. We report here a case of Rosai-Dorfman disease presenting with massive right cervical lymphadenopathy.


Factors predicting the time until atrial fibrillation recurrence after concomitant left atrial ablation.
Treatment of atrial fibrillation, a risk factor for morbidity and mortality, by left atrial ablation is a less complex procedure which is increasingly performed in conjunction with surgery for various heart diseases. Although restoration of sinus rhythm is effective initially, atrial fibrillation may recur. We investigated factors predicting the time until its recurrence. Between January 2003 and December 2005, 162 consecutive patients (52.5% male, age 69+/-8.7 years) with permanent atrial fibrillation underwent concomitant left atrial ablation and isolated or combined mitral valve surgery (42.6%), isolated or combined aortic valve surgery (32.1%), and isolated or combined coronary artery bypass grafting (24.1%). Ablation was performed by microwave (n=93, 57.4%) or radiofrequency (n=69, 42.6%) technology. Follow-up was after 3, 6, 12 months and yearly thereafter. Predictive values of variables for postoperative atrial fibrillation were examined using techniques of univariate and multivariate survival analysis (proportional hazards regression). Eight patients died perioperatively and 13 during follow-up (not ablation related). Two patients were lost to follow-up. At last follow-up (19+/-11.3 months), 86 patients (62%) were in stable sinus rhythm, 73 (52%) without antiarrhythmic drugs, and 43 (31%) were in atrial fibrillation. Predictors for the time until recurrence of atrial fibrillation in a multivariate model were preoperative atrial fibrillation duration (hazard ratio 1.005, 95% confidence interval 1.003-1.007, p<0.001) and left atrial diameter (hazard ratio 1.056, 95% confidence interval 1.020-1.093, p=0.002). Overall, sinus rhythm conversion rate was 75% when preoperative atrial fibrillation duration was less than 2 years, but 42% in longer lasting atrial fibrillation with left atrial dilatation (>50mm). Age, gender, primary heart disease, history of thromboembolism or cardioversion, presence of concomitant diseases, EuroScore, left ventricular size and function, aortic cross-clamp time, ablation technology, and treatment with antiarrhythmic drugs did not predict rhythm outcome. Preoperative atrial fibrillation duration and left atrial diameter predict the time until atrial fibrillation recurrence after concomitant left atrial ablation, whereas age, type of primary cardiac surgery, ablation technology and antiarrhythmic therapy do not.


Tailored eHealth Lifestyle Promotion: Which Behavioral Modules Do Users Prefer?
Health risk behaviors are widespread among adults and often co-occur. eHealth computer-tailored technology provides individuals with personalized feedback regarding multiple lifestyle behaviors. First, the authors investigated individuals' preferences for particular lifestyle modules and hypothesised that health preventive behavior modules would be preferred over addictive behavior modules. Second, characteristics associated with these choices were examined. A web-based questionnaire assessed demographics, health status, and five lifestyle behaviors (i.e., physical activity, fruit consumption, vegetable consumption, alcohol intake and tobacco use) among adults (N = 1,828). Responses were translated into a health risk appraisal outlining whether respondents adhered to the national guidelines for these behaviors. Next, respondents could select one of the lifestyle modules providing personalized advice. More than 60% of the participants failed to meet the guidelines for more than one lifestyle behavior. The physical activity module was the most popular, followed by the smoking and fruit modules. Young adults tended to prefer the physical activity and fruit modules, whereas the vegetable module was more popular among older adults. No consistent pattern was identified for the alcohol and smoking modules. The results support the authors' hypothesis that health preventive behaviors-in particular, physical activity-would be preferred. Although this could imply that physical activity could serve as a gateway behavior when aiming at multiple behavior changes, it is also conceivable that other mechanisms, such as the actual success of behavior change, or the fact that people can choose, may increase chances of multiple behavior change. Hence, mechanisms leading to multiple behavior change need to be further explored.


Combined effects of the contraceptive hormones, ethinyl estradiol and levonorgestrel, on the use of place and response memory in gonadally-intact female rats.
During maze navigation rats can rely on hippocampus-mediated place memory or striatum-mediated response memory. Ovarian hormones bias whether females use place or response memory to reach a reward. Here, we investigated the impact of the contraceptive hormones, ethinyl estradiol (EE) and levonorgestrel (LNG), on memory bias. A total of 63 gonadally-intact female rats were treated with either 10 μg/kg of EE alone, 20 μg/kg of LNG alone, both 10 μg/kg of EE and 20 μg/kg of LNG together, or a sesame oil injection with 5% ethanol as a vehicle control. Rats in the control condition were tested during the diestrus phase of the estrous cycle in order to control for the low circulating levels of gonadotropin and ovarian hormones that occur with oral contraceptive administration. Rats treated with LNG alone had a bias towards the use of place memory compared to diestrus phase control rats. This bias was not observed if LNG was administered in combination with EE. Rats treated with EE or EE+LNG did not have a statistically significant difference in memory bias compared to rats in the control group. These data show that synthetic hormones contained in oral contraceptives administered to females influence which cognitive strategy is predominantly used during navigation.


Different cholinergic pathways are involved in the improvement induced by CCK-8 and by ACTH-(1-24) in massive acute hemorrhage, in rats.
Cholecystokinin octapeptide (CCK-8) (20 micrograms/kg i.v.) and tetracosactide [ACTH-(1-24)] (160 micrograms/kg i.v.) restore blood pressure and allow rats subjected to otherwise invariably fatal acute hemorrhage to survive. Atropine sulphate (2-8 mg/kg i.p.), which crosses the blood-brain barrier, dose-dependently prevents this effect both in the case of ACTH-(1-24) and in that of CCK-8. On the other hand, atropine methyl bromide (2-8 mg/kg i.p.), which does not cross the blood-brain barrier, prevents the effect in the case of CCK-8, but not in that of ACTH-(1-24). These data suggest that a cholinergic mechanism is involved in the anti-shock effect of both ACTH-(1-24) and CCK-8, though the sites of action appear to be in the CNS, in the case of ACTH-(1-24), and outside the CNS, in that of CCK-8.


Analogical versus rule-based classification.
Sensitivity to feature co-occurrences was investigated as a function of analytic and analogical transfer. Participants memorized descriptions of hypothetical people and were then induced either to make transfer decisions by analogy to the descriptions (analogical transfer) or to search for and apply rules (analytic transfer). Across three experiments, analogical transfer was found to be more effective than analytic transfer for preserving co-occurring features in classification judgements. This result held for a variety of category structures and stimulus materials. It was difficult for subjects who adopted an analytic-transfer strategy to identify regularities that were embedded in stored instances. Alternatively, subjects who adopted an analogical-transfer strategy preserved feature co-occurrences as an indirect result of similarity-based retrieval and comparison processes. The effectiveness of analytic and analogical transfer is discussed.


Association between sleep duration and cardiometabolic factors in adolescents.
The sleep reduction can change healthy people's hemodynamic control and cardiovascular regulation through increased inflammatory response and altered endothelial function. The objective the study to analyze the association between sleep duration and cardiometabolic risk factors in adolescents in the birth cohort of São Luís (1997/98). This is a cross-sectional study with adolescents participating in the birth cohort of São Luís (1997/98). Sleep duration was evaluated using accelerometer data (Actigraph wGT3X-BT). Glycemia, systolic blood pressure (SBP), diastolic blood pressure (DBP), total cholesterol, low-density lipoprotein cholesterol (LDL-c), high-density lipoprotein cholesterol (HDL-c) and triglycerides were considered cardiometabolic factors. The Directed Acyclic Graph (DAG) was used to identify the minimum set of adjustment for confounding. Out of 1,268 adolescents, 50.3% of them were male. The prevalence of sleep duration of less than 6 h per day was 31.1%. The mean glycemia value was 91.8 mg/dL (± 15.9), DBP was 71.3 mmHg (± 7.5), SBP was 114.9 mmHg (± 12.3), HDL was 48.5 mg/dL (± 11.6), LDL was 89.0 mg/dL (± 25.7), the total cholesterol was 156.0 mg/dL (± 31.1), and triglycerides was 93.6 mg/dL (± 47.2). The crude analysis showed an association between sleep duration and SBP and LDL-c. In the adjusted analysis, the associations did not remain. Our study showed no association between sleep duration and cardiometabolic outcomes in adolescents.


Intermittent cardiac troponin-I screening is an effective means of surveillance for a perioperative myocardial infarction.
Several studies suggest that cardiac troponin-I (cTn-I) is a more sensitive indicator of cardiac injury compared with other biochemical markers of injury, but the strategy with the highest diagnostic yield (true positive and true negative) for perioperative surveillance is unknown. The authors undertook a prospective evaluation of the perioperative incidence of myocardial infarction (MI) and evaluated surveillance strategies for the diagnosis of MI. Prospective, cohort study. Two university hospitals. Four hundred sixty-seven high-risk patients requiring noncardiac surgery. None. The diagnosis of myocardial injury was determined by cardiac protein markers combined with either postoperative changes on 12-lead electrocardiography or 1 of 3 clinical symptoms consistent with MI (chest pain, dyspnea, requirement for hemodynamic support). A receiver operating characteristic curve evaluating troponin in the diagnosis of MI revealed a value of 2.6 ng/mL as having the highest sensitivity and specificity. The sensitivity and specificity of cTn-I value > or =2.6 ng/mL, troponin > or =1.5 ng/mL, total creatine kinase (CK) > or =170 IU/L with MB > or =5%, and CK-MB > or =8 ng/mL were compared. Surveillance strategies were determined on a subset of patients (n = 257). The incidence of MI was 9.0% by cTn-I > or =2.6 ng/mL criteria, 19% by cTn-I > or =1.5 ng/mL, 13% by CK-MB mass, and 2.8% by CK-MB%. The specificity of cTn-I > or =2.6 ng/mL as an indicator of MI was 98%, and its positive predictive value (PPV) was 85%. Cardiac troponin-I > or =2.6 ng/mL had equal specificity but greater PPV than the cTn-I > or =1.5 ng/mL (specificity 98% and PPV 79%). If surveillance of cTn-I > or =2.6 ng/mL was used to detect MI, then the strategy with the highest diagnostic yield was surveillance on postoperative days 1, 2, and 3. Perioperative cardiac injury continues to occur frequently after noncardiac surgery, as detected by cTn-I. Serial monitoring of cardiac troponin-I on postoperative days 1, 2, and 3 provides the strategy with the highest diagnostic yield for surveillance of MI.


Bilateral Calculi in a Child With Bilateral Single System Ureteroceles.
Ureteroceles in children are detected with prenatal sonography and less commonly during the evaluation following a urinary tract infection. Rarely do ureteroceles in the pediatric population present with stones, particularly in a bilateral fashion. We present a case of a 5-year-old boy found to have bilateral intravesical single system ureteroceles harboring multiple large calculi treated successfully with a staged endoscopic approach.