Generic sample preparation and dual polarity liquid chromatography-time-of-flight mass spectrometry for high-throughput screening in doping analysis.
The requirements on initial testing in doping control are getting tighter regarding efficiency and speed while the scope of analytes is getting more diverse and, consequently, the need for high-throughput methods is apparent. In this study, a comprehensive screening method for doping agents in human urine is presented, based on solid phase extraction (SPE) and liquid chromatography-time-of-flight mass spectrometry (LCTOFMS). The method covers most of the compound groups in the list of prohibited substances by World Anti-Doping Agency (WADA). Mixed-mode SPE on two types of sorbent and the use of negative ionization mode besides the commonly used positive mode in electrospray ionization (ESI) allowed detection of acidic compounds, such as sulpho-conjugated metabolites. A run time of 8 minutes for each of the two ESI polarities was achieved. The method was validated regarding relative ionization efficiency, selectivity and signal to noise at the WADA's minimum required performance limit (MRPL) level, resulting in the acceptance of 197 compounds. A selection of 20 compounds was submitted for a more thorough validation, including extraction recovery, repeatability and linearity. Recovery and linearity (R(2)) varied mainly between 83-115% and 0.78-0.99, respectively. Median values for repeatability at the MRPL and 10 x MRPL levels were below 20%. A mean and median mass accuracy of 1.2 and 0.80 mDa, respectively, was achieved. The present method represents at the moment the widest coverage of low molecular weight prohibited substances for the screening in sports, providing an approach for further rationalisation of the analytical work-flow in the doping control laboratories.


Metastatic Basal cell carcinoma accompanying gorlin syndrome.
Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.


Top-down processes during auditory phoneme categorization in dyslexia: a PET study.
While persistence of subtle phonological deficits in dyslexic adults is well documented, deficit of categorical perception of phonemes has received little attention so far. We studied learning of phoneme categorization during an activation H(2)O(15) PET experiment in 14 dyslexic adults and 16 normal readers with similar age, handedness and performance IQ. Dyslexic subjects exhibited typical, marked impairments in reading and phoneme awareness tasks. During the PET experiment, subjects performed a discrimination task involving sine wave analogues of speech first presented as pairs of electronic sounds and, after debriefing, as syllables /ba/ and /da/. Discrimination performance and brain activation were compared between the acoustic mode and the speech mode of the task which involved physically identical stimuli; signal changes in the speech mode relative to the acoustic mode revealed the neural counterparts of phonological top-down processes that are engaged after debriefing. Although dyslexic subjects showed good abilities to learn discriminating speech sounds, their performance remained lower than those of normal readers on the discrimination task over the whole experiment. Activation observed in the speech mode in normal readers showed a strongly left-lateralized pattern involving the superior temporal, inferior parietal and inferior lateral frontal cortex. Frontal and parietal subparts of these left-sided regions were significantly more activated in the control group than in the dyslexic group. Activations in the right frontal cortex were larger in the dyslexic group than in the control group for both speech and acoustic modes relative to rest. Dyslexic subjects showed an unexpected large deactivation in the medial occipital cortex for the acoustic mode that may reflect increased effortful attention to auditory stimuli.


Evaluation of functional stability of quercetin as a raw material and in different topical formulations by its antilipoperoxidative activity.
The present study evaluates the antioxidant activity of the flavonol quercetin, and its functional stability as a raw material and when added in formulations. The iron-chelating activity was determined using the bathophenanthroline assay, and the functional stability was evaluated with the antilipoperoxidative assay. Raw material presented concentration-dependent antilipoperoxidative and iron-chelating activities. The initial antilipoperoxidative activity of the raw material, cream and gel-cream were 63%, 78%, and 69%, respectively. There was no detectable loss of activity during 182 days (6 months) of storage at all tested temperatures (4°C, room temperature [RT], 37°C, and 45°C) for the raw material. Considering the method variability of 10%, activity loss greater than 10% for nonionic cream was detected after 126 days at 4°C (20.1%), decreasing thereafter to 22.2% after 182 days. At 45°C, the loss of activity started after 182 days (13.2%). For the anionic gel-cream, activity loss started after 84 days (28.4%, 45°C), decreasing after 182 days to 40.3% at 45°C. At 37°C, activity loss was detected after 182 days (12%). In conclusion, the results suggest that the activity of quercetin depends on iron chelation, and its posible usefulness as a topical antioxidant to prevent oxidative stress-induced skin damage depends on maintaining its antilipoperoxidative activity stored at RT, which avoids special storage conditions.


Dermatofibrosarcoma protuberans of the breast: A case report.
Dermatofibrosarcoma protuberans (DFSP) is a rare malignant tumor of subcutaneous tissue characterized by slow infiltrative growth. The tumor occurs in patients of all ages, with the highest frequency occurring between the second and the fifth decades of age. Genetically, DFSP is characterized by a reciprocal translocation t(17;22)(q22;q13), or more often, as a supernumerary ring chromosome involving chromosomes 17 and 22. Standard treatment of a localized tumor is surgical excision with wide margins. In the present study, a case report of a 43-year-old woman with a growing tumor in the left breast is discussed. The patient underwent breast-conserving surgery. Histological and cytogenetic examinations of the tumor resulted in a diagnosis of DFSP. The clinical and morphological characteristics of the tumor, in addition to the treatment options, were also evaluated.


[Investigation and analysis for current situation and pathogenesis relevant to pulmonary hypertension].
To investigate the demographic characteristics and the causes for pulmonary hypertension (PH) in adult patients. Methods: A total of 2 508 adult patients diagnosed as PH, who came from the Second Xiangya Hospital of Central South University from January 2010 to December 2014, were retrospectively investigated. All subjects underwent the clinical diagnosis, or the echocardiographic diagnosis, or thetraditional hemodynamic criteria by right heart catheterization (RHC). The patient's data including hospital numbers, gender, ages, primary diseases, etc, are collected and analyzed. Results: In this study, the number of patients diagnosed as PH was increased year by year. The median age of 2 508 patients was 47 (18-93) years old, and there were 933 males (37.2%), the ratio of male to female was 1:1.69 (P<0.05). Female was more common in Class I PH (pulmonary arterial hypertension) and Class II PH (pulmonary hypertension due to left heart disease)(>70%), but there were more male patients (74.5%) in Class III PH (pulmonary hypertension due to lung diseases and/or hypoxia). In our study, 896 cases (35.73%) were the Class I PH, 1 163 cases was the Class II PH (46.37%), 411 cases was the Class III PH (16.39%), and the Class IV PH (chronic thromboembolic pulmonary hypertension) and the Class V PH (PH with unclear and/or multifactorial mechanisms) were diagnosed in 32(1.27%) and 6 patients (0.24%), respectively.The diseases with largest number of patients for the top 7 primary PH were rheumatic heart disease (1 090, 43.48%), congenital heart disease (692, 27.60%), chronic obstructive pulmonary disease (358, 14.28%), connective tissue related disease(156, 6.22%), valvular heart disease (66, 2.63%), idiopathic PH (46, 1.83%) and pulmonary embolism (27, 1.08%). Conclusion: Adult PH patients' peak incidence age is 41-50 years old. This disease is more common among women, and the Class I/II PH are common in women while the Class III is more common in men. Rheumatic heart disease and congenital heart disease may be the most common cause for pulmonary hypertension in China, and chronic obstructive pulmonary disease is the most common cause for the Class III PH, in which the patients are old.


High dietary calcium causes metabolic alkalosis in egg-type pullets.
One hundred sixty healthy egg-type pullets were randomly divided into 2 groups at 35 d of age. The groups were fed either with a normal-calcium (control, 8.5 g of Ca/kg) diet or with a high-calcium (HC, 36.3 g of Ca/kg) diet, respectively. The experiment lasted for 32 d. The healthy situations of the egg-type pullets were observed. Blood gas values and serum and urine electrolyte content were determined. The HC diet caused watery excreta in pullets. The pullets raised on the HC diet had significantly higher blood pH, bicarbonate, base excess, and significantly lower blood partial pressure of oxygen, partial pressure of carbon dioxide, and oxygen saturation than the pullets raised on the control diet. Phosphorus and potassium decreased; meanwhile, calcium increased in the HC group as compared with the control group. Sodium, magnesium, and chloride in serum had no significant difference between the HC group and the control. The pullets raised on the HC diet had significantly higher urine pH than the pullets raised on the control diet. For HC pullets, urinary concentration and 24-h urinary excretion of calcium and chloride was significantly higher, and magnesium, inorganic phosphorus, and sodium was significantly lower than that of the control pullets. It is concluded that some metabolic disorders associated with high dietary calcium in egg-type pullets may be related to a state of metabolic alkalosis.


Adaptive modulation of adult brain gray and white matter to high altitude: structural MRI studies.
The aim of this study was to investigate brain structural alterations in adult immigrants who adapted to high altitude (HA). Voxel-based morphometry analysis of gray matter (GM) volumes, surface-based analysis of cortical thickness, and Tract-Based Spatial Statistics analysis of white matter fractional anisotropy (FA) based on MRI images were conducted on 16 adults (20-22 years) who immigrated to the Qinghai-Tibet Plateau (2300-4400 m) for 2 years. They had no chronic mountain sickness. Control group consisted of 16 matched sea level subjects. A battery of neuropsychological tests was also conducted. HA immigrants showed significantly decreased GM volumes in the right postcentral gyrus and right superior frontal gyrus, and increased GM volumes in the right middle frontal gyrus, right parahippocampal gyrus, right inferior and middle temporal gyri, bilateral inferior ventral pons, and right cerebellum crus1. While there was some divergence in the left hemisphere, surface-based patterns of GM changes in the right hemisphere resembled those seen for VBM analysis. FA changes were observed in multiple WM tracts. HA immigrants showed significant impairment in pulmonary function, increase in reaction time, and deficit in mental rotation. Parahippocampal and middle frontal GM volumes correlated with vital capacity. Superior frontal GM volume correlated with mental rotation and postcentral GM correlated with reaction time. Paracentral lobule and frontal FA correlated with mental rotation reaction time. There might be structural modifications occurred in the adult immigrants during adaptation to HA. The changes in GM may be related to impaired respiratory function and psychological deficits.


How to improve the prediction of quadrupled semitendinosus and gracilis autograft sizes with magnetic resonance imaging and ultrasonography.
Hamstring tendon grafts may have an unacceptable size for use in anterior cruciate ligament (ACL) reconstruction. Magnetic resonance imaging (MRI) has been proposed to predict the diameters of hamstring tendon grafts. Preoperative ultrasonography (US) might reliably anticipate intraoperative 4-strand semitendinosus and gracilis tendon (4ST-GT) graft sizes similarly to MRI. An MRI evaluation of the hamstring tendons with a higher magnification may improve the accuracy of the method. Cohort study (diagnosis); Level of evidence, 2. A total of 33 patients undergoing ACL reconstruction with a 4ST-GT graft and MRI performed at our institution were included. The cross-sectional area (CSA) of each semitendinosus tendon (ST) and gracilis tendon (GT) was calculated preoperatively with US and with MRI under 2× and 4× magnification. Intraoperative measurement of the final diameter of the 4ST-GT using a closed-hole sizing block with 0.5-mm increments was made. Pearson correlation coefficients were calculated to determine the relationship between the final intraoperative graft diameter of the 4ST-GT and the CSA of the ST and GT measured with US and MRI with 2× and 4× magnification. Simple linear regression was also calculated to attempt to predict the graft diameter based on given measurements. There were statistically significant correlations between the measured CSA with US and both MRI magnifications with the 4ST-GT diameter. However, MRI under 4× magnification showed a much higer correlation (0.86) than MRI under 2× magnification (0.54) or US (0.51). Final graft diameters ≥8 mm were observed in 80.8% of patients with a CSA >14 mm(2), in 76.9% of patients with a CSA >25 mm2, and in 96.2% of patients with a CSA >17 mm2 measured with US, 2× magnification of MRI, and 4× magnification of MRI, respectively. Preoperative calculation of the CSA of the hamstring tendons with MRI and US can help to reliably estimate 4ST-GT grafts. In terms of correlation of the CSA with graft diameter, US was comparable to 2× MRI, but 4× MRI showed a much greater accuracy. Threshold values of the CSA of the ST and GT of 25 mm2, 17 mm2, and 14 mm2 with the 2× MRI, 4× MRI, and US methods, respectively, are needed to reliably predict a 4ST-GT graft with a minimum diameter of 8 mm.


[Growth of the caudate nucleus during postnatal ontogeny in the dog, rat and guinea pig].
The development of one of the largest nuclei in the basal ganglia -- the caudate nucleus -- in the dog, rat and guinea pig continues after birth. The growth processes of the neural cell bodies in the caudate nucleus coinside with the development of the animal's movement performed by itself and are most intensive up to the ontogenetic stage, when in all three species the brain mass is equal to 60% of the brain mass in a mature animal. An indirect index demonstrating the dendritic network development -- the density of the neurons arrangement -- becomes equal to the value specific for a mature animal much later in the postnatal ontogenesis even in a full-term born guinea pig. The postponed morphological maturation of the structure can be considered as an evidence of a certain connection of the structure in question not only with motor activity, but with inhibition, as well.


Masking of random-walk motion by flicker, and its role in the allocation of motion in the on-line jitter illusion.
Typically, perceptual stabilization mechanisms make us unaware of the retinal image motion produced by the small, involuntary eye movements our eyes constantly make during fixation. The breakdown of perceptual stability is demonstrated by the on-line jitter illusion, in which a circular static pattern appears to jitter coherently when surrounded by a flickering annular pattern. Although both regions of the stimulus are subject to retinal motion from eye movements, the visual system attributes this motion to the central static region in the form of visual jitter, while the surrounding flickering region remains perceptually stable. We investigated factors influencing this allocation of motion and reference frame in the on-line jitter illusion. The flickering of the surround was found to impair the detection of simultaneous random-walk motion in this area, giving a detection reliability of around 80% for motion approximating that from fixational eye movements. Changes to spatial texture and location of flicker (centre vs. surrounding annulus) had little effect on the final percept. However, use of a nonconcentric stimulus resulted in a marked reduction in apparent jitter in all subjects. Our results suggest for the on-line jitter illusion, allocation of motion and reference frame is influenced by the general principle that, if one region surrounds another, the surrounding region tends to be allocated as the frame of reference. When this factor is controlled for, spatial textures, location of flicker, and the masking of motion by flicker have a smaller but measurable influence on the final percept.


Effects of selective logging on bat communities in the southeastern Amazon.
Although extensive areas of tropical forest are selectively logged each year, the responses of bat communities to this form of disturbance have rarely been examined. Our objectives were to (1) compare bat abundance, species composition, and feeding guild structure between unlogged and low-intensity selectively logged (1-4 logged stems/ha) sampling grids in the southeastern Amazon and (2) examine correlations between logging-induced changes in bat communities and forest structure. We captured bats in understory and canopy mist nets set in five 1-ha study grids in both logged and unlogged forest. We captured 996 individuals, representing 5 families, 32 genera, and 49 species. Abundances of nectarivorous and frugivorous taxa (Glossophaginae, Lonchophyllinae, Stenodermatinae, and Carolliinae) were higher at logged sites, where canopy openness and understory foliage density were greatest. In contrast, insectivorous and omnivorous species (Emballonuridae, Mormoopidae, Phyllostominae, and Vespertilionidae) were more abundant in unlogged sites, where canopy foliage density and variability in the understory stratum were greatest. Multivariate analyses indicated that understory bat species composition differed strongly between logged and unlogged sites but provided little evidence of logging effects for the canopy fauna. Different responses among feeding guilds and taxonomic groups appeared to be related to foraging and echolocation strategies and to changes in canopy cover and understory foliage densities. Our results suggest that even low-intensity logging modifies habitat structure, leading to changes in bat species composition.


Neuroprotective effect of N-acetylcysteine on neuronal apoptosis induced by a synthetic gingerdione compound: involvement of ERK and p38 phosphorylation.
Besides being used as a spice, ginger has been applied in oriental medicine to ameliorate symptoms such as inflammatory, rheumatic disorders, and gastrointestinal discomforts. The effects of ginger on neuronal cells, however, have not been explored. We investigate the effect of 1-(3,4-dimethoxyphenyl)-3,5-dodecenedione (I(6)), a derivative of gingerdione, on cultured cortical neurons. After a 5-day maturation period in vitro, cortical neurons were treated with I(6) for 24 hr and cell viability was assessed using MTT assay. I(6) induced neuronal death in a concentration-dependent manner. Hoechst 33342, propidium iodide (PI), and TUNEL staining confirmed that the reduced cell viability by I(6) was due to apoptosis. Pre-treatment of cell with N-acetylcysteine (NAC) prevented cell death in a concentration-dependent manner. N-acetylcysteine increased phosphorylated levels of p42 and p44 extracellular signal-regulated kinases (ERKs). In parallel, farnesyltransferase and MEK inhibitors blocked ERK phosphorylation and neuroprotective effect of NAC. Unexpectedly, NAC also increased phosphorylated level of p38 mitogen-activated protein kinase (MAPK) and p38 specific inhibitors dose-dependently attenuated the effect of NAC. Farnesyltransferase and MEK inhibitors completely abolished NAC-induced p38 phosphorylation whereas p38 inhibitor did not influence NAC-induced ERK phosphorylation. These results show that NAC serially activates ERKs and p38 MAPK, and ERKs and p38 work together to mediate the neuroprotective effect of NAC.


Diagnostic pearls in the management of vitreomacular disorders.
The posterior precortical vitreous pocket is a premacular liquefied lacuna that is physiologically present in adult eyes. The posterior wall of the pocket consists of a thin layer of the vitreous, and its anterior border is delineated by vitreous gel. This peculiar structure of the premacular vitreous cortex plays a key role in the development of various vitreomacular disorders. In diabetic retinopathy, fibrovascular tissue tends to develop along the outer margin of the pocket, resulting in a ring- or c-shaped structure. Tangential contraction of the posterior wall of the pocket or premacular cortex causes the formation of macular holes. The posterior wall of the pocket serves as a major structural component of idiopathic premacular fibrosis. The concept of the posterior precortical vitreous pocket provides a guideline to manage vitreoretinal disorders occurring in the macular area.


Successful endoscopic submucosal dissection of gastric carcinoid in a patient with autoimmune gastritis and systemic lupus erythematosus.
A 41-year-old woman was referred with epigastric discomfort. She had a 20-year history of SLE. Esophagogastroduodenoscopy (EGD) examination showed severe atrophic gastritis in the stomach and a protruding lesion was detected. Histological examination showed a carcinoid tumor with cytoplasmic staining with chromogranin-A. Using an endoscopic submucosal dissection (ESD) technique, en bloc resection of the tumor was performed. No recurrence has been found for 3 years after the treatment. Type I gastric carcinoid can occur at an earlier age with AIG and autoimmune diseases such as systemic lupus erythematosus (SLE). This is the first report of gastric carcinoid that was treated by ESD.


[New methods for the evaluation of bone quality. Nanoindentation protocol for measurement of bone mechanical properties of material level.]
Bone is an inhomogeneous, anisotropic natural biomaterial with complex, multiscale structural variations. Thus, experiments on the bulk scale using a universal testing machine are not applicable for localized precision mechanical testing of bone. Nanoscale mechanical testing technologies such as nanoindentation enables to assess the intrinsic toughening mechanism of bone, which is a function of the highly-organized matrix proteins within the mineralized nanostructure. Understanding the basic nanomechanical properties of calcified tissues will help us to appreciate general concepts associated with the excellent design of advanced engineering materials and engineered tissues.


Sufficiency of longitudinal moment of inertia for haptic cylinder length judgments.
Many studies invoke moment of inertia (Iii) as necessary and sufficient information to perceive cylinder length via wielding, yet some assert that Iii is neither necessary (weight, m, or static moment, M, are sufficient) nor sufficient for length judgments (m or M is necessary). Mathematical expressions for Iii not involving m or M imply length, so Iii could be sufficient for cylinder length judgments. In 5 experiments (N = 113), only longitudinal Iii (the smallest principal value) informed cylinder length estimates in a novel task, rolling. Experiment 1 yielded reliable length judgments. Varying diameter supported length scaling (Experiment 2); similar length estimates occurred with both rolling and wielding (Experiment 3); feedback improved rolling length judgments to levels commensurate with wielding (Experiment 4); and length judgments shifted predictably with added mass (Experiment 5). Contrary to proposals in the literature, Iii is sufficient information for cylinder length judgments, absent m or M information, even when Iii is of minimal magnitude and the task quite novel.


Retrieval of ventricular catheter with the aid of endoscopy: technical note.
Multilocular hydrocephalus usually requires placement of multiple ventricular catheters for the treatment of secondary cysts and intraventricular septation. The formation of strong adhesions can embed the catheters so that they cannot be removed without a higher risk of intraventricular hemorrhage. Moreover, the devices could represent a nidus for infection and a risk for formation and enlargement of intraventricular secondary cysts. Neuroendoscopy allows the surgeon safely to reach the ventricular catheters that have been left or lost in the ventricular cavity, and to remove them via a minimally invasive approach. In this paper, the authors document another application of ventricular endoscopy in the management of this kind of hydrocephalus. The removal of an unnecessary and no longer useful prosthetic device that is a possible focus of infection justifies endoscopic treatment, which, in this experience, is not associated with morbidity.


Malabsorption Syndromes.
Malabsorption syndrome refers to the small intestines' inability to absorb certain nutrients and fluids. There are several common associated disorders, which may present with subtle and/or overt symptoms. With subtle symptoms, it is difficult to determine the cause, making diagnosis difficult or even inaccurate. Malabsorption can originate from an immune response, an inflammatory process, or alternation of the small intestines by surgical methods. This article reviews common malabsorption disease processes of the small bowel and the resulting pathophysiology. Diagnostic studies, treatment, and prognosis of various conditions within the malabsorption disease state are discussed.


[Prevalence survey of smoking pattern among peasants in China].
To study smoking patterns among farmers so as to provide scientific basis for developing effective tobacco control measures via policy making. The Survey was conducted by randomly selecting, in multi-stage, about 50 thousand farmers aged over 15 years old as the participants of the study according to economic status and geographical distribution in Guangdong, Henan, Jiangsu, Qinghai and Heilongjiang provinces. Results The overall prevalence of smoking was 33.45% (prevalence in men was 56.94% and in women was 6.40%) showing a decrease of 5%, 10% and -2.5% as compared with those of in 1996 survey. The average number of cigarettes consumed per day by men and women was 16 and 13 respectively as compared with 15 and 11 in 1996. Smoking prevalence among farmers in China was still remarkably high. The measures for tobacco control in rural areas should be emphasized. For reducing this prevalence, health promotion strategy might be prioritized.


Epstein-Barr virus-specific cytoskeletal early antigen in EBV-transformed cell lines.
An Epstein-Barr virus (EBV)-specific determinant of early antigen (EA) character was found to be associated with intermediate filaments of EBV genome-activated cells. This determinant was defined with a murine monoclonal antibody (MAb) and with human MAb derived from lymphoblastoid cell lines of patients with acute infectious mononucleosis (IM). Such patients' antibodies either recognized intermediate filament determinants in general, or were restricted to the intermediate filament determinant of EBV genome-activated cells, as also recognized with the 1B6 murine MAb. The 1B6 determinant was a component of EA as defined by phosphonoacetate-resistance, methanol-sensitivity, and various co-staining and antibody-blocking experiments. While anti-intermediate filament antibodies have been reported after various viral illnesses, the 1B6 and some patients' antibodies recognize an EBV-specific determinant which might function in the lytic cycle of these cells.


Dataset for Genome Sequencing and De Novo Assembly of the Candidate Phyla Radiation in Supragingival Plaque.
The Candidate Phyla Radiation (CPR), as a newly discovered and difficult-to-culture bacterium, accounts for the majority of the bacterial domain, which may be related to various oral diseases, including dental caries. Restricted by laboratory culture conditions, there is limited knowledge about oral CPR. Advances in metagenomics provide a new way to study CPR through molecular biology. Here, we used metagenomic assembly and binning to reconstruct more and higher quality metagenome-assembled genomes (MAGs) of CPR from oral dental plaque. These MAGs represent novel CPR species, which differed from all known CPR organisms. Relative abundance of different CPR MAGs in the caries and caries-free group was estimated by mapping metagenomic reads to newly constructed MAGs. The relative abundance of two CPR MAGs was significantly increased in the caries group, indicating that there might be a relationship with caries activity. The detection of a large number of unclassified CPR MAGs in the dataset implies that the phylogenetic diversity of CPR is enormous. The results provide a reference value for exploring the ecological distribution and function of uncultured or difficult-to-culture microorganisms.


Should the Erector Spinae Plane Block Be Applied in the Pain Management of Percutaneous Nephrolithotomy?
Introduction This prospective, randomized controlled study aimed to investigate the efficacy and respiratory effects of postoperative pain management with an erector spinae plane block in patients undergoing percutaneous nephrolithotomy. Methods Sixty American Society of Anesthesiologists (ASA) I-II patients aged 18-65 years, scheduled to undergo percutaneous nephrolithotomy, were randomized either to the erector spinae plane block (ESPB) or control group. Fifteen mL 0.5% bupivacaine at the T11 level was administered preoperatively using the in-plane technique in the ESPB group. In both groups, 1 gr of intravenous paracetamol was administered intraoperatively. Postoperative pain and agitation were evaluated using the visual analog scale (VAS), dynamic VAS at zero, six, and 24 hours, and the Riker sedation-agitation scale at the 0th hour after surgery. Peak expiratory flow rate (PEFR) and oxygen saturation (SpO2) were measured in preoperative examination and at the 0th, 6th, and 24th hours postoperatively. The time and number of the analgesic requirement, mobilization, and discharge time were also recorded. Results A significantly lower VAS and dynamic VAS were observed at the 0th, 6th, and 24th hours in the ESPB group (p<0.05 for each timepoint). The postoperative/preoperative PEFR ratio was lower and there were more agitated patients in the control group (p<0.05). Conclusion An erector spinae plane block may have additional clinical advantages while providing effective analgesia in patients who underwent percutaneous nephrolithotomy compared to intravenous analgesia.


Purification of sulforaphane from Brassica oleracea seed meal using low-pressure column chromatography.
Sulforaphane is an isothiocyanate that is present naturally in widely consumed Brassica oleracea vegetables and has been shown to block the formation of tumors. The contents of sulforaphane in five groups of B. oleracea seeds (broccoli, Brussels sprouts, cabbage, cauliflower and kale) were determined by RP-HPLC using linear gradient of acetonitrile in water. A new low-cost method to isolate and purify natural sulforaphane from B. oleracea seed meal was described in this work. Crude sulforaphane was first separated from B. oleracea seed meal by using immiscible solvent extraction with ethyl acetate, 10% ethanol and hexane, and the crude sulforaphane was used as raw materials to prepare high purity sulforaphane by low-pressure column chromatography of silica gel (200-300 mesh) with different eluents and elution modes. Compared with these different elution methods, the gradient elution was preferable to the isocratic elution for reducing the elution time and the eluent consumption and increasing the purity of sulforaphane product. The purity and recovery of sulforaphane were more than 90% in gradient elution.


Impacts of Absolute and Relative Income on Self-Rated Health in Urban and Rural China.
This study aims to assess the impacts of absolute and relative income on self-rated health (SRH) of residents in rural and urban China. Data were derived from the China Health and Nutrition Survey. Three distinct measures of relative income were considered (Gini coefficient, Yitzhaki index, and Deaton index) and computed for 3 geographic units (nation, province, and community). Nonlinear dynamic models for panel data were employed to test the absolute and relative income hypotheses. Absolute income was significantly associated with SRH among urban and rural populations. Relative income, as measured by the Gini coefficient, the Yitzhaki index, and the Deaton index, had statistically significant and negative impacts on SRH among the rural population, regardless of the reference group. For the urban population, the Gini coefficient was associated with SRH regardless of the reference group. In contrast, only the Yitzhaki index and the Deaton index at the provincial level were associated with SRH among the urban population. Our findings may provide a reference for policymakers to implement health policies designed to improve population health.


Large eddy simulation of droplet transport and deposition in the human respiratory tract to evaluate inhalation risk.
As evidenced by the worldwide pandemic, respiratory infectious diseases and their airborne transmission must be studied to safeguard public health. This study focuses on the emission and transport of speech-generated droplets, which can pose risk of infection depending on the loudness of the speech, its duration and the initial angle of exhalation. We have numerically investigated the transport of these droplets into the human respiratory tract by way of a natural breathing cycle in order to predict the infection probability of three strains of SARS-CoV-2 on a person who is listening at a one-meter distance. Numerical methods were used to set the boundary conditions of the speaking and breathing models and large eddy simulation (LES) was used for the unsteady simulation of approximately 10 breathing cycles. Four different mouth angles when speaking were contrasted to evaluate real conditions of human communication and the possibility of infection. Breathed virions were counted using two different approaches: the breathing zone of influence and direction deposition on the tissue. Our results show that infection probability drastically changes based on the mouth angle and the breathing zone of influence overpredicts the inhalation risk in all cases. We conclude that to portray real conditions, the probability of infection should be based on direct tissue deposition results to avoid overprediction and that several mouth angles must be considered in future analyses.


Readability assessment of package leaflets of biosimilars.
To assess the degree of readability and the length of the package leaflets of biosimilars. The package leaflets analysed were downloaded from the European Medicines Agency (EMA) website. The study sample included the package leaflets written in English of all the biosimilars that were authorised by the EMA on 31 August 2017, and whose content was available via the internet on that date (n=35). This was a cross-sectional analytical study. The readability of the package leaflets of all biosimilars authorised by the EMA in August 2017 was determined applying the Flesch and Flesch-Kincaid formulas. The influence of the following variables on the readability and length was also analysed: package leaflet section, type of biosimilar, date of first authorisation of the biosimilar and type of medicine. A considerable variation of the package leaflets length was found (3154±803). The readability of all the package leaflets overtook the recommended value for health-related written materials taking into account Flesch-Kincaid Index, and none of the package leaflets were easy to understand according to the Flesch Index. Statistically significant differences (p<0.05) were observed between the sections of package leaflets in readability indices and length. The most difficult sections to understand were those related with the therapeutic indication of medicine and the possible side effects. Package leaflets for authorised biosimilars may not fulfil the function for which they were designed. The competent organisations could be informed about the possible negative effect on the use of this type of medicines.


[Radiological methods in the diagnostics of extrinsic allergic alveolitis].
There were 77 patients with EAA under our observation with the following X-ray symptom groups: emphysematous-interstitial; parenchymatous-interstitial; pneumonic. The emphysematous-interstitial X-ray symptom group is the most non-specific for the X-ray diagnostics. The changes indicate to symptoms of impaired bronchial conductance of different expression and are relevant to clinical EAA options characteristic for the obstructive syndrome. The parenchymatous-interstitial X-ray symptom group is more characteristic for occupational EAA. In such cases the most important are changes in the lung parenchyma that have a diffusive character and are accompanied by general symptoms indicating to bronchial impairments of different severity. In pneumatic X-ray symptom group, the major X-ray symptom is presence of local sites of lung tissue consolidation of hypoventilation-infiltrative character that can be bilateral, multiple with a trend to migration.


Sickle cell erythrostasis and non-specific hepatitis and peritonium tubercle hyperplasia. Case report.
Hepatic and bile duct involvement are common in sickle cell disease. This is a histopathological case report of a 40 year old female with sickle cell non-specific hepatitis and peritoneum tubercle hyperplasia. The histopathology diagnosis of liver biopsy was erythrostasis and non-specific hepatitis and for peritoneal tubercle was non-specific chronic inflammation with mesothelial hyperplasia. Involvement in a subgroup of patients with SCD. Hepatic and bile duct involvement are common in sickle cell disease. It is recommended that for dyspeptic SCD patients diagnostic labroscopy could be helpful in the diagnosis of peritoneal tubercle, therefore for performing the histopathology of peritoneal tubercle biopsy sections.


Use of inertial sensors for ambulatory assessment of center-of-mass displacements during walking.
Current methods for center-of-mass (CoM) estimation are restricted to gait laboratories. The aim of this study was to estimate CoM displacement under ambulatory conditions with inertial sensors. A sacral inertial sensor (SIS method) was used to estimate the CoM displacement by double integration of the acceleration. Overestimation of the displacement caused by pelvic rotations was compensated (CSIS method). The CoM displacement estimations using the (C)SIS method were compared to the conventional methods of the segmental analysis (SA) method and the sacral marker (SM) method by the intraclass correlations and the root-mean-square (RMS) differences between the CoM curves. Accurate ambulatory measurement of the CoM displacement using inertial sensors was possible. Estimations of the sacrum position using the SIS method and the SM method were similar with mean (SD) RMS differences of 3.23 (0.87), 2.96 (0.42), and 3.22 (0.78) mm for, respectively, the x-, y- and z-directions. The CoM estimation of the SIS method has RMS differences of 5.67 (1.20), 7.16 (3.28), and 3.49 (1.29) mm compared the SA method. The CSIS method shows a clear improvement in these estimations of the CoM with RMS differences of 5.52 (1.29), 4.44 (1.89), and 3.17 (1.41) mm and is generally applicable for healthy subjects.


Aging erythrocyte membranes as biomimetic nanometer carriers of liver-targeting chromium poisoning treatment.
Chromium poisoning has become one of the most common heavy metal poisoning occupational diseases with high morbidity and mortality. However, most antidotes detoxify the whole body and are highly toxic. To achieve hepato-targeted chromium poisoning detoxification, a novel hepato-targeted strategy was developed using aging erythrocyte membranes (AEMs) as biomimetic material coated with a dimercaptosuccinic acid (DMSA) nanostructured lipid carrier to construct a biomimetic nano-drug delivery system. The particle size, potential, drug loading, encapsulation rate, in vitro release, and stability of the nanoparticles (NPs) were characterized. Confocal microscopy and flow cytometry showed that the prepared NPs could be phagocytized by RAW264.7 macrophage cells. The efficacy of AEM-DMSA-NPs for targeted liver detoxification was evaluated by in vitro MTT analysis and an in vivo model of chromium poisoning. The results showed that the NPs could safely and efficiently achieve targeted liver chromium poisoning detoxification. All the results indicated that the biomimetic nano-drug delivery system mediated by aging erythrocyte membranes and containing DMSA nanoparticles could be used as a novel therapeutic drug delivery system potentially targeting liver detoxification.


Using proteomics to mine genome sequences.
We present a method for mining unannotated or annotated genome sequences with proteomic data to identify open reading frames. The region of a genome coding for a protein sequence is identified by using information from the analysis of proteins and peptides with MALDI-TOF mass spectrometry. The raw genome sequence or any unassembled contigs of an organism are theoretically cleaved into a number of equal sized but overlapping fragments, and these are then translated in all six frames into a series of virtual proteins. Each virtual protein is then subjected to a theoretical enzymatic digestion. Standard proteomic sample preparation methods are used to separate, array, and digest the proteins of interest to peptides. The masses of the resulting peptides are measured using mass spectrometry and compared to the theoretical peptide masses of the virtual proteins. The region of the genome responsible for coding for a particular protein can then be identified when there are a large number of hits between peptides from the protein and peptides from the virtual protein. The method makes no assumptions about the location of a protein in a particular gene sequence or the positions or types of start and stop codons. To illustrate this approach, all 773 proteins of Pseudomonas aeruginosa contained in SWISS-PROT were used to theoretically test the method and optimize parameters. Increasing the size of the virtual proteins results in an overall improvement in the ability to detect the coding region, at the cost of decreasing the sensitivity of the method for smaller proteins. Increasing the minimum number of matching peptides, lowering the mass error tolerance, or increasing the signal-to-noise ratio of the simulated mass spectrum, improves the ability to detect coding regions. The method is further demonstrated on experimental data from Mycobacterium tuberculosis and is also shown to work with eukaryotic organisms (e.g., Homo sapiens).


Loss of muscle strength during aging studied at the gene level.
Age-related muscle wasting and increased frailty is a major socioeconomic as well as a major medical problem. In our quest to extend the quality of life it is important to increase the strength of elderly people sufficiently so they can carry out everyday tasks and prevent them falling and breaking bones that are brittle because of osteoporosis. Muscles generate the mechanical strain that contributes to the maintenance of other musculoskeletal tissues and a vicious cycle is established when the muscles start to produce less force resulting in more bone loss and weakening of tendons. Another aspect that is less well appreciated is that muscle acts as a dynamic, metabolic store. In a traumatic situation, muscle provides amino acids to aid tissue repair processes and maintaining acid-base balance. At the present time there are strategies in addition to exercise for preventing age-related muscle wasting and these are briefly reviewed. Here, more attention is paid to the role of the growth hormone/insulin-like growth factor-1 (GH/IGF-1) axis and the discovery of mechano-growth factor (MGF). This is derived from the IGF-1 gene by alternative splicing and in the young is responsible for increasing contractile strength in response to exercise by activating the muscle satellite (stem) cells that kick-start local muscle repair and induce hypertrophy. Recent studies including gene transfer of this part of the IGF-1 gene and unique MGF peptides offer the prospect of treating muscle wasting during the aging process as well as muscle cachexia associated with many diseases.


13. Studies in rating the physical, mental, and social dysfunction of the chronically ill aged.
It is difficult to separate what might be considered the normal from the dysfunctional aspects of aging in the physical, mental, and social areas, and wide variation occurs in the way persons age, with and without chronic illness. One cannot, and would not want to, disentangle these interrelated areas, but they are often measured as if they were independent of each other. Any assessment of the total functioning of an individual must take into account the subject's own perception of his health or functional status which, in addition to the cultural influences and feedback from the environment, interact to produce total adjustment. There is some indication that self-assessments of health may be a reliable predictor of more detailed functional assessments. Lastly, there is a plea for the study of a multidimensional approach including objective and subjective physical, mental, and social measurements related to patient outcome. With currently available statistical methods, it may be possible to reduce the number of variables needed for assessment of the total person to a few that uniquely describe overall status.


In vivo Screen Identifies Zdhhc2 as a Critical Regulator of Germinal Center B Cell Differentiation.
Germinal center (GC) B cell differentiation is critical for the production of affinity-matured pathogen-specific antibodies, the dysregulation of which may lead to humoral immunodeficiency or autoimmunity. The development of an in vivo screening system for factors regulating GC B cell differentiation has been a challenge. Here we describe a small-scale in vivo screening system with NP-specific B1-8hi cells and a retroviral shRNA library targeting 78 candidate genes to search for B cell-intrinsic factors that specifically regulate GC B cell differentiation. Zdhhc2, a gene encoding palmitoyltransferase ZDHHC2 and highly expressed in GC B cells, is identified as a strong positive regulator of GC B cell differentiation. B1-8hi cells transduced with Zdhhc2-shRNA are severely compromised in differentiating into GC B cells. A further analysis of in vitro differentiated B cells transduced with Zdhhc2-shRNA shows that Zdhhc2 is critical for the proliferation and the survival of B cells stimulated by CD40L, BAFF, and IL-21 and consequently impacts on their differentiation into GC B cells and post-GC B cells. These studies not only identify Zdhhc2 as a novel regulator of GC B cell differentiation but also represent a proof of concept of in vivo screen for regulators of GC B cell differentiation.


Effect of AMP-activated protein kinase activation on cardiac fibroblast proliferation induced by coxsackievirus B3.
Excessive fibroblast proliferation and collagen production are the major pathogenic mechanisms in the progression of viral myocarditis, which is most frequently associated with infection by coxsackievirus B3 (CVB3). AMP-activated protein kinase (AMPK) has been confirmed to be involved in the progression of myocardial remodeling. However, it remains unclear whether AMPK has an effect on CVB3-induced cardiac fibroblast proliferation. In the present study, the effects of AMPK on cardiac fibroblast proliferation and collagen secretion induced by CVB3 were investigated. Proliferation of neonatal cardiac fibroblasts was determined by cell counting and detection of newly synthesized DNA in cells, and the proportion of cells in the S phase was measured. Hydroxyproline ELISA was used to detect collagen secretion. Phosphorylation of AMPKα-Thr172 was evaluated by western blotting. It was found that neonatal cardiac fibroblasts were clearly proliferating markedly and secreting collagen at 24 h after CVB3 infection, and peaked at 48 h. These effects were inhibited following pretreatment of the fibroblasts with 5-aminoimidazole-4-carboxamide-ribonucleoside (AICAR), a specific AMPK activator, for 2 h prior to CVB3 infection. However, if the cells were preincubated with compound C for 30 min, the inhibitive effects of AICAR were reversed. Western blotting results indicated that AMPK α-Thr172 phosphorylation was increased by AICAR and attenuated by Compound C. The results of the present study suggest that CVB3 infection increases cardiac fibroblast proliferation and collagen secretion, and that these phenomena can be inhibited by activated AMPK. These findings contribute to our understanding of AMPK function and the future design of therapeutic approaches for the treatment of cardiac fibrosis caused by chronic viral infection, such as CVB3-induced myocarditis.


Tandem Wittig rearrangement/aldol reactions for the synthesis of glycolate aldols.
A new tandem Wittig Rearrangement/aldol reaction of O-benzyl or O-allyl glycolate esters is described. This reaction generates two carbon-carbon bonds and two contiguous stereocenters in a single step from simple starting materials. The [1,2]-Wittig rearrangement proceeds under very mild reaction conditions that do not require the use of a strong base, and the 1,2-diol products are obtained in good yield with excellent diastereoselectivity (>20:1).


Impact of Fighting on Antibody Response to Hepatitis B Virus Vaccine in Mice.
Antibody responses to vaccines can be influenced by various behavioral and psychosocial factors. Few reports exist on the impact of fighting on antibody response to vaccines. This study unexpectedly found that fighting could significantly enhance antibody production in male mice immunized with hepatitis B virus (HBV) vaccines. To confirm the finding, a mouse-fighting model was established in which it was observed that only intense fighting, not mild fighting, enhanced the antibody response to HBV surface antigen in male mice, and that the frequency of fighting and active attacks during fighting showed no obvious relationship with the antibody levels in the male mice that experienced fighting. In addition, fighting can cause significant upregulation of CD80 in CD11c(+) cells in the spleen of male mice. These data suggest that fighting could influence the humoral immune response in individuals immunized with vaccines or infected with microbes.


Low Bone Density and Bisphosphonate Use and the Risk of Kidney Stones.
Previous studies have demonstrated lower bone density in patients with kidney stones, but no longitudinal studies have evaluated kidney stone risk in individuals with low bone density. Small studies with short follow-up reported reduced 24-hour urine calcium excretion with bisphosphonate use. We examined history of low bone density and bisphosphonate use and the risk of incident kidney stone as well as the association with 24-hour calcium excretion. We conducted a prospective analysis of 96,092 women in the Nurses' Health Study II. We used Cox proportional hazards models to adjust for age, body mass index, thiazide use, fluid intake, supplemental calcium use, and dietary factors. We also conducted a cross-sectional analysis of 2294 participants using multivariable linear regression to compare 24-hour urinary calcium excretion between participants with and without a history of low bone density, and among 458 participants with low bone density, with and without bisphosphonate use. We identified 2564 incident stones during 1,179,860 person-years of follow-up. The multivariable adjusted relative risk for an incident kidney stone for participants with history of low bone density compared with participants without was 1.39 (95% confidence interval [95% CI], 1.20 to 1.62). Among participants with low bone density, the multivariable adjusted relative risk for an incident kidney stone for bisphosphonate users was 0.68 (95% CI, 0.48 to 0.98). In the cross-sectional analysis of 24-hour urine calcium excretion, the multivariable adjusted mean difference in 24-hour calcium was 10 mg/d (95% CI, 1 to 19) higher for participants with history of low bone density. However, among participants with history of low bone density, there was no association between bisphosphonate use and 24-hour calcium with multivariable adjusted mean difference in 24-hour calcium of -2 mg/d (95% CI, -25 to 20). Low bone density is an independent risk factor for incident kidney stone and is associated with higher 24-hour urine calcium excretion. Among participants with low bone density, bisphosphonate use was associated with lower risk of incident kidney stone but was not independently associated with 24-hour urine calcium excretion.


Thoracoscopic Repair of Esophageal Atresia.
Background: Esophageal atresia (EA) is a rare congenital malformation of the esophagus. Surgical treatment is required to restore the continuity of the esophagus. This can be performed through thoracotomy. However, an increasing number of hospitals is performing minimal invasive surgery (MIS). In this article, we describe the technique of thoracoscopic repair of EA in neonates in more detail and show the outcome of a patient cohort operated by young pediatric surgeons in training. Methods: Between 2014 and 2019 correction was performed in 64 EA type C patients at the UMC Utrecht, Wilhelmina Children's Hospital, mainly by young pediatric surgeons in training. Results: All patients were corrected through MIS, 3 days after birth. The median operation duration was 181 (127-334) minutes. Nasogastric tube feeding was started on the first postoperative day, and oral feeding 6 days postop. Postoperative complications included leakage (14.1%), stenosis (51.1%), and recurrent tracheoesophageal fistula (7.8%). Conclusion: Thoracoscopic repair of EA can be performed safely, with good outcome and all the benefits of MIS. However, it remains a challenging procedure and should be performed only in pediatric centers with a vast experience in MIS, especially when training young pediatric surgeons. These centers must have access to a multidisciplinary team of neonatologists, pediatric anesthesiologists, surgeons, and ENT specialists to ensure the best possible care in hemodynamic, respiratory, and cerebral monitoring and gastrointestinal and developmental outcome.


[On the hemispheric asymmetry of unilateral spatial neglect].
Many investigators were interested in unilateral spatial neglect (USN) and studied it in various respects. Especially the between-hemispheric difference of USN has been broadly argued. It can be considered as a well accepted fact that there is a difference of frequency of USN between left and right brain-damaged patients, however, there is no consistent opinion whether there are differences of severity and quality. To settle this dispute, 239 right-handed unilateral brain-damaged subjects were investigated on USN. 125 subjects suffered from left hemisphere lesions and 114 from right hemisphere lesions. Two tests; copy of drawings and finger imitation; were performed. On copying of drawings, each patient was required to copy line drawings of cubes, complex two-dimensional geometrical figures and simple two-dimensional geometrical figures. Those who failed to complete either the left- or right-hand side of any one of these drawings were classified as showing USN. Then failures of USN were divided into two different patterns; unilateral omission and unilateral distorsion. Again imitation of various finger patterns was tested with the hand homolateral to lesions. These items were presented by two methods. The subjects saw the dorsal side of the examiner's hand in the first, and palmar side in the second. On the copying of drawings, right brain-damaged subjects had about twice higher incidence of total USN than left brain-damaged subjects. As for omission alone, the incidence with the right hemispheric group was three times as high as the incidence with the left hemispheric group.(ABSTRACT TRUNCATED AT 250 WORDS)


Identification of calmodulin-like activity in term human amnion: effect of calmodulin inhibitors on prostaglandin biosynthesis.
Human amnion prostaglandin E2 (PGE2) synthesis increases with the onset of labour, and this synthesis is Ca2+-dependent. To understand better the mechanism of Ca2+-stimulated PGE2 biosynthesis, studies were performed to identify the presence of the intracellular Ca2+-mediator, calmodulin, in human amnion and to examine its role in PGE2 synthesis. Calmodulin-like activity was identified by the ability of the microsomal and cytosolic fractions of the 105,000g centrifugation of amnion homogenate to stimulate cyclic AMP-dependent phosphodiesterase activity. Cytosolic fractions consistently stimulated phosphodiesterase activity more than microsomal fractions (P less than 0.001) in paired samples from term human amnions. This activity was calcium-dependent. The cytosolic and microsomal factors increased the Vmax but not the Km of phosphodiesterase. There were no differences in these parameters with the onset of labour. The distribution of calmodulin-like activity between microsomes and cytosol was similar to the distribution of calmodulin mass as determined by radioimmunoassay. Three structurally different inhibitors of calmodulin activity, calmidazolium, trifluoperazine and W7, were tested for their ability to inhibit cytosolic factor-stimulated phosphodiesterase activity and to inhibit PGE2 output from dispersed amnion cells obtained before the onset of labour at term (cesarean section cells) or after spontaneous labour and vaginal delivery (spontaneous labour cells). The 50% inhibitory concentrations of the calmodulin antagonists in the phosphodiesterase assay were: trifluoperazine (6.7 microM), calmidazolium (0.11 microM), and W7 (24 microM). Trifluoperazine inhibited both basal and calcium ionophore (A23187)-stimulated PGE2 output from cesarean section cells and spontaneous labour amnion cells. Calmidazolium inhibited basal PGE2 output in cesarean section cells and spontaneous labour cells, but had no effect on A23187-stimulated output. W7 inhibited only the ionophore-stimulated PGE2 output in cesarean section amnion cells. The rank order of inhibition of both phosphodiesterase activation and basal PGE2 output was: calmidazolium greater than trifluoperazine greater than W7. These results suggest that human amnion contains calmodulin and that its distribution, concentration and activity remain unchanged with the onset of labour. The data suggest, although not conclusively, that calmodulin may, in part, play a role in amnion cell PGE2 production. Further investigation of calmodulin effects upon specific enzymes in the PGE2 synthetic pathway will be necessary to elucidate a role for calmodulin in PGE2 production.


[Application of diffusion-weighted echo planar imaging for diagnosis of small acute and subacute brain ischemic lesions].
The aim of this study was to determine the utility of diffusion-weighted echo planar imaging (DW-EPI) for detecting acute and subacute brain ischemic foci less than 2 cm in size. Thirty patients underwent DW-EPI on a 1.5 T superconducting unit using a SE-EPI sequence with an arbitrary pair of Stejskal-Tanner gradients applied along the imaging axes. DW-EPI demonstrated all the mast recent ischemic lesions as areas of decreased diffusion, providing greater conspicuity and larger size than conventional spin-echo imaging. DW-EPI is a promising method to detect within a subsecond early ischemia and reversible ischemic changes that are not demonstrate on routine spin-echo images.


Treatment of Glioma in the 21st Century: An Exciting Decade of Postsurgical Treatment Advances in the Molecular Era.
The past decade has brought about major changes in the way we classify and have begun to approach patients with high-grade glioma. As we trend toward personalized medicine, we are now able to utilize the molecular characteristics of each individual's tumor in order to tailor their treatment, particularly if the patient is elderly or has a poor performance status at baseline. We address the state of the practice as of 2016 in regard to chemotherapy, immunotherapy, and tumor-treating fields. The goal of this review is to enhance readers' understanding of the nuances that are allowing clinicians to tailor the treatment of high-grade glioma more specifically.


Detection of bone loss with different X-ray techniques in periodontal patients.
Intraoral radiographs can aid in formulating a more accurate diagnosis of periodontal disease. However, it must be considered whether a comparable amount of information can be obtained with modern panoramic radiographs. The aim of this study was to determine to what degree the diagnosable amount of bone loss in patients with aggressive periodontitis or severe chronic periodontitis depends on the type of x-ray technique used. A total of 110 subjects (63 females) were included in this study. The inclusion criteria were the diagnosis of aggressive periodontitis (N = 49) or severe chronic periodontitis (N = 61). In all patients, panoramic radiographs (panoramic) and intraoral films of all regions (eight to 10 single exposures) were available. Analysis of the panoramic and intraoral films was carried out with a computer-assisted technique for linear measurement. The amount of bone loss in reference to the alveolar crest (AC) and bottom of the bony defect (BD) was determined as a percentage of total root length. Depending on the examined tooth and reference point, 47.01% to 81.89% of all subjects showed differences between intraoral and panoramic measurements that were < or =10% of the total root length. For cemento-enamel junction-AC measurements, differences between intraoral and panoramic measurements that were >10% of the total root length were found predominantly in the upper molar and premolar regions. In the mandible, differences between intraoral and panoramic measurements that were >10% of the total root length were observed for BD and AC at the mesial contour of the central incisor. A preorientation with respect to the expected bone loss is possible using panoramic radiographs. Additional intraoral films might be helpful where rapid changes of bone level are expected (e.g., aggressive periodontitis).


Hydrate kinetics study in the presence of nonaqueous liquid by nuclear magnetic resonance spectroscopy and imaging.
The dynamics of methane hydrate growth and decomposition were studied by nuclear magnetic resonance (NMR) spectroscopy and imaging (MRI). Three well-known large molecule guest substances (LMGS) were used as structure H hydrate formers: 2,2-dimethylbutane (NH), methylcyclohexane (MCH), tert-butyl methyl ether (TBME). In addition, the impact of a non-hydrate former (n-heptane/nC7) was studied. The methane diffusion and hydrate growth were monitored by recording the 2H NMR spectra at 253 K and approximately 4.5 MPa for 20 h. The results revealed that methane diffuses faster in TBME and NH, slower in nC7, and slowest in MCH. The TBME system gives the fastest hydrate formation kinetics followed by NH, MCH, and nC7. The conversion of water into hydrate was also observed. The imaging study showed that TBME has a strong affinity toward ice, which is not the case for the NH and MCH systems. The degree of ice packing was also found to affect the LMGS distribution between ice particles. Highly packed ice increases the mass transfer resistance and hence limits the contact between LMGS and ice. It was also found that "temperature ramping" above the ice point improves the conversion significantly. Finally, hydrates were found to dissociate quickly within the first hour at atmospheric pressure and subsequently at a much slower rate. Methane dissolved in LMGS was also seen. The residual methane in hydrate phase and dissolved in LMGS phase explain the faster kinetics during hydrate re-formation.


Estimated genetic parameters for carcass traits of Brahman cattle.
Heritabilities and genetic and phenotypic correlations were estimated from feedlot and carcass data collected from Brahman calves (n = 504) in central Florida from 1996 to 2000. Data were analyzed using animal models in MTDFREML. Models included contemporary group (n = 44; groups of calves of the same sex, fed in the same pen, slaughtered on the same day) as a fixed effect and calf age in days at slaughter as a continuous variable. Estimated feedlot trait heritabilities were 0.64, 0.67, 0.47, and 0.26 for ADG, hip height at slaughter, slaughter weight, and shrink. The USDA yield grade estimated heritability was 0.71; heritabilities for component traits of yield grade, including hot carcass weight, adjusted 12th rib backfat thickness, loin muscle area, and percentage kidney, pelvic, and heart fat were 0.55, 0.63, 0.44, and 0.46, respectively. Heritability estimates for dressing percentage, marbling score, USDA quality grade, cutability, retail yield, and carcass hump height were 0.77, 0.44, 0.47, 0.71, 0.5, and 0.54, respectively. Estimated genetic correlations of adjusted 12th rib backfat thickness with ADG, slaughter weight, marbling score, percentage kidney, pelvic, and heart fat, and yield grade (0.49, 0.46, 0.56, 0.63, and 0.93, respectively) were generally larger than most literature estimates. Estimated genetic correlations of marbling score with ADG, percentage shrink, loin muscle area, percentage kidney, pelvic, and heart fat, USDA yield grade, cutability, retail yield, and carcass hump height were 0.28, 0.49, 0.44, 0.27, 0.45, -0.43, 0.27, and 0.43, respectively. Results indicate that sufficient genetic variation exists within the Brahman breed for design and implementation of effective selection programs for important carcass quality and yield traits.


Twenty-Year Trajectories of Physical Activity Types from Midlife to Old Age.
Correlates of physical activity (PA) vary according to type. However, predictors of long-term patterns of PA types into old age are unknown. This study aimed to identify 20-yr trajectories of PA types into old age and their predictors. Seven thousand seven hundred thirty-five men (age, 40-59 yr) recruited from UK towns in 1978 to 1980 were followed up after 12, 16, and 20 yr. Men reported participation in sport/exercise, recreational activity and walking, health status, lifestyle behaviors and socio-demographic characteristics. Group-based trajectory modeling identified the trajectories of PA types and associations with time-stable and time-varying covariates. Men with ≥3 measures of sport/exercise (n = 5116), recreational activity (n = 5085) and walking (n = 5106) respectively were included in analyses. Three trajectory groups were identified for sport/exercise, four for recreational activity and three for walking. Poor health, obesity and smoking were associated with reduced odds of following a more favorable trajectory for all PA types. A range of socioeconomic, regional and lifestyle factors were also associated with PA trajectories but the magnitude and direction were specific to PA type. For example, men with manual occupations were less likely to follow a favorable sport/exercise trajectory but more likely to follow an increasing walking trajectory compared to men with nonmanual occupations. Retirement was associated with increased PA but this was largely due to increased sport/exercise participation. Physical activity trajectories from middle to old age vary by activity type. The predictors of these trajectories and effects of major life events, such as retirement, are also specific to the type of PA.


ApoE4 allele is associated with late-life depression: a population-based study.
This study aimed to clarify the relationship between the epsilon4 allele and late-life depression, taking into account lipid profile, vascular diseases, and sociodemographics. Using a multilevel stratified random sampling strategy, a total of 500 subjects aged 65 to 74 years were recruited for this cross-sectional study from the official household records of an entire county in southern Taiwan. Depressive symptoms were assessed by the Taiwanese Depression Questionnaire (TDQ). Cognitive function was assessed by the Short Portable Mental Status Questionnaire. Blood samples were collected for the determination of the apolipoprotein E (ApoE) polymorphism and the lipid profile. A total of 283 subjects (58.7% male, with a mean age of 69.2 +/- 2.7 years) completed all questionnaires and collection of blood samples. Using the chi(2) test, the overall difference for frequency of the presence of the epsilon4 allele was significant among the severe group (TDQ score >18), moderate group (TDQ score 9-18), and mild group (TDQ score <9). The proportion of history of heart disease was significantly higher in the severe group than in the mild or moderate group. Kruskal-Wallis statistics revealed that the mean total and low-density lipoprotein cholesterol levels were significantly higher in the severe group than in the moderate or mild group. With our two-level four-class latent class regression model, the presence of the epsilon4 allele was significantly associated with the severely depressed group as compared to the nondepressed group, adjusting for vascular diseases and lipid profile. The ApoE epsilon4 allele may be correlated with severe depression in the elderly through ways other than the "vascular depression" hypothesis.


Identification of serines-1035/1037 in the kinase domain of the insulin receptor as protein kinase C alpha mediated phosphorylation sites.
A new site of serine phosphorylation (Ser-1035/1037) has been identified in the kinase domain of the insulin receptor. Mutant receptors missing these two serines were expressed in Chinese hamster ovary cells overexpressing protein kinase C alpha. These mutant receptors lacked a phorbol ester-stimulated phosphoserine containing tryptic peptide as demonstrated by both high percentage polyacrylamide/urea gel electrophoresis and two-dimensional tlc. Moreover, a synthetic peptide with the sequence of this tryptic peptide was phosphorylated by isolated protein kinase C alpha and co-migrated with the phosphopeptide from in vivo labeled receptor. These results indicate that serine-1035 and/or 1037 in the kinase domain of the insulin receptor are phosphorylated in response to activation of protein kinase C alpha.


CRISPR/Cas9-mediated generation of a Plac8 knockout mouse model.
Placenta specific 8 (PLAC8, also known as ONZIN) is a multi-functional protein that is highly expressed in the intestine, lung, spleen, and innate immune cells, and is involved in various diseases, including cancers, obesity, and innate immune deficiency. Here, we generated a Plac8 knockout mouse using the CRISPR/Cas9 system. The Cas9 mRNA and two single guide RNAs targeting a region near the translation start codon at Plac8 exon 2 were microinjected into mouse zygotes. This successfully eliminated the conventional translation start site, as confirmed by Sanger sequencing and PCR genotyping analysis. Unlike the previous Plac8 deficient models displaying increased adipose tissue and body weights, our male Plac8 knockout mice showed rather lower body weight than sex-matched littermate controls, though the only difference between these two mouse models is genetic context. Differently from the previously constructed embryonic stem cell-derived Plac8 knockout mouse that contains a neomycin resistance cassette, this knockout mouse model is free from a negative selection marker or other external insertions, which will be useful in future studies aimed at elucidating the multi-functional and physiological roles of PLAC8 in various diseases, without interference from exogenous foreign DNA.


How advanced practice registered nurse practice barriers impact health care access in Michigan.
Despite the Affordable Care Act increasing the number of insured individuals in Michigan, many individuals cannot access care as the state continues to have a provider shortage that is likely to get worse. It is well documented that when individuals lack primary care access, their health suffers. Advanced practice registered nurses (APRN) could help reduce the state's health care shortage, as the care they provide is safe, cost effective, and high quality. Unfortunately, Michigan's APRN practice restrictions limit these professionals from autonomously providing care to the underserved and rural populations that need them the most. Indeed, Michigan is behind other states that offer full practice authority to APRNs, and its health outcomes reflect this stance. Eliminating the restrictive practice environment in Michigan will give citizens better access to primary care.


Growth hormone promotes glomerular lipid accumulation in bGH mice.
Bovine growth hormone (bGH) transgenic mice develop progressive glomerulosclerosis and exhibit abnormalities in hepatic lipid metabolism. We have previously shown that growth hormone up-regulates the low-density lipoprotein (LDL) receptor and 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGR) in mouse mesangial cells. However, a role of lipid abnormalities in bGH kidney disease has not yet been demonstrated. Groups of bGH mice (5 and 11 months old) presenting with, respectively, moderate and severe degrees of glomerulosclerosis were compared to age-matched controls. Neutral lipid content in kidney cortex was determined by oil red-O staining, serum cholesterol, and triglycerides by enzymatic assays, relative mRNA expression of LDL receptors, HMGR, and scavenger receptor by real-time reverse transcription-polymerase chain reaction (RT-PCR), and HMGR protein expression by immunoblotting. Two younger (5 and 12 weeks old) groups of mice were used to study scavenger receptor expression at earlier time points. Serum cholesterol was significantly increased in bGH mice at 5 months, but triglycerides were lower than control levels at both 5 and 11 months. Renal cortex HMGR expression was elevated at the mRNA but not at the protein level in the 11-month-old bGH group compared to controls. However, glomerular neutral lipid staining and scavenger receptor mRNA expression were markedly increased in all bGH mice, including those at 5 weeks of age compared to respective controls. The bGH mouse exhibits an increased mesangial lipid content and elevated scavenger receptor mRNA expression as early as at 5 weeks of age, suggesting that an increased kidney uptake of oxidized LDL could play a role in the development of glomerulosclerosis in this mouse model.


Tumor-Induced Osteomalacia Caused by a Phosphaturic Mesenchymal Tumor of the Sole Presenting as a Crippling Illness in a Postmenopausal Woman.
Tumor-induced osteomalacia, a rare and intriguing paraneoplastic syndrome that is usually caused by a phosphaturic mesenchymal tumor, leads to severe pain and hypophosphatemia. However, during clinical practice, most patients suffer from significant delay of diagnosis and treatment because the symptoms are similar to those of some very common diseases, such as osteoporosis and osteoarthritis. Moreover, physical complaints from postmenopausal women usually exacerbate the possibility of such delays. We describe a case of a postmenopausal woman with crippling bone pain and weakness, who had been diagnosed with a case of simple osteoporosis and osteoarthritis for 3 years, even with fine-needle aspiration biopsy of the offending phosphaturic mesenchymal tumor. After surgical removal of the 2 × 3-cm2 tumor in her sole, we observed immediate relief of her systemic symptoms, with visual analogue scale improvement from 5 of 10 preoperatively to 2 of 10 5 days after surgery. There were no signs of recurrence during 2-year follow-up. This case highlights the significance of thorough history-taking as a fundamental tool for diagnosis even in the era of advanced technology, and that the awareness of tumor-induced osteomalacia should be raised. Otherwise, such a small localized soft tissue mass would seldom be associated with the severe systemic symptoms.


Effects of calcitonin, katacalcin, and calcitonin gene-related peptide on basal and TSH-stimulated thyroid hormone secretion in the mouse.
It is known that transcripts of the calcitonin gene in the thyroid C cells are processed to mRNAs generating precursors for the three peptides, calcitonin, katacalcin, and calcitonin gene-related peptide (CGRP), and that these peptides are produced and secreted from the C cells. The present study investigated the effects of these three peptides on basal and TSH-stimulated thyroid hormone secretion in the mouse, according to the McKenzie technique. Mice were pre-treated with 125I and thyroxine. Calcitonin (3 nmol animal-1) reduced the basal blood radioiodine levels to 72 +/- 5% compared to 95 +/- 6% in controls (P less than 0.01). This effect is likely to be renal, since calcitonin significantly increased the renal excretion of a concomitantly injected 125I load. In contrast, katacalcin and CGRP were without effect on basal blood radioiodine levels. All three peptides (1 or 3 nmol animal-1) were without effect on TSH (70 microU animal-1)-induced increase in blood radiodine levels. However, when the peptides were given together (either two and two concomitantly, or all three together), the TSH-induced increase in blood radioiodine levels was inhibited. This inhibition of TSH-induced thyroid hormone secretion might represent an intrathyroidal regulatory mechanism of the follicular cell activity.


Involvement of the genitourinary system in multiple primary malignant neoplasms: a review.
A case is presented of a patient with separate primaries of the cervix, breast, bladder, and kidney. In a review of 352,073 cancer patients in the literature, the genitourinary system appears to be at a greater risk of this phenomenon. The entity of multiple primary malignant neoplasms is reviewed with an analysis of the involvement of the genitourinary system.


Nitrogen and phosphorus flux rates from sediment in the lower St. Johns River estuary.
Internal cycling of nutrients from the sediment and water column can be an important contribution to the total nutrient load of an aquatic ecosystem. Our objective was to estimate the internal nutrient loading of the Lower St. Johns River (LSJR). Dissolved reactive phosphorus (DRP) and ammonium (NH(4)-N) flux from sediments were measured under aerobic and anaerobic water column conditions using intact cores, to estimate the overall contribution of the sediments to P and N loading to the LSJR. The DRP flux under aerobic water column conditions averaged 0.13 mg m(-2) d(-1), approximately 37 times lower than that under anaerobic conditions (4.77 mg m(-2) d(-1)). The average NH(4)-N released from the anaerobic cores (18.03 mg m(-2) d(-1)) was also significantly greater than in the aerobic cores for all sites and seasons, indicating the strong relationship between nutrient fluxes and oxygen availability in the water column. The mean annual internal DRP load was estimated to be 330 metric tons (Mg) yr(-1), 21% of the total P load to the river, while the mean annual internal load of NH(4)-N was determined to be 2066 Mg yr(-1), 28% of the total N load to the LSJR estuary. As water resource managers reduce external loading to the LSJR the frequency of anaerobic events should decline, thereby reducing nutrient fluxes from the sediment to the water column, reducing the internal loading of DRP and NH(4)-N. Results from this study demonstrate that the internal flux of nutrients from sediments may be a significant portion of the total load and should be accounted for in the total nutrient budget of the river for successful restoration.


Determining the pathogenicity and virulence of parasites on animal models.
The aim of this review is to present various animal organisms used to determine the pathogenicity and virulence of old and new human and animal pathogens based on animal studies, cell cultures, macrophages and other models. The animal models presented in this study, in addition to the most popular organisms such as the laboratory mouse, rat, guinea pig and monkey, are also less popular models, such as zebrafish (Danio rerio) or chicken embryos in eggs. These animals are used to study the pathogenicity of parasites such as Acanthamoeba, Naegleria fowlerii, Toxoplasma gondii, Entamoeba histolytica and Besnoitia caprae and other species. In addition to animal models, we also present models using cell cultures, macrophages and computer methods. We also answer questions about what experimental methods allow to differentiate species and populations in terms of pathogenicity and virulence.


Real-time reverse transcriptase-polymerase chain reaction detection and analysis of nucleotide sequences coding for a neutralizing epitope on infectious bursal disease viruses.
We used real-time reverse transcriptase (RT)-polymerase chain reaction (PCR) to detect infectious bursal disease virus (IBDV) strains. The LightCycler (Roche) and hybridization probe system (Roche, Molecular Biochemicals) were used. A mutation probe labeled with fluorescein and an anchor probe labeled with Red-640 dye were prepared for each of the STC, Del E, D78, and Bursine 2 viral sequences. The mutation probes were designed to hybridize to nucleotides that encode the hydrophilic B region of VP2 for each virus. The anchor probes were designed to a relatively conserved region immediately downstream from the mutation probes. When hybridized to the RT-PCR product, a mutation and anchor probe pair produced fluorescence resonance energy transfer that was detected by the LightCycler instrument. Because they were designed to have a lower melting temperature (Tm), the mutation probes dissociated from the template before the anchor probes. The Tm values of the four mutation probes for each of their homologous viruses (exact sequence match) were STC, 69.3 +/- 1.2 C; D78, 67.8 +/- 0.9 C; Del E, 65.5 +/- 0.6 C; and Bursine 2, 71.7 +/- 0.4 C. These values were compared with the Tm values observed for a particular probe and heterologous virus. If the Tm values observed for heterologous viruses were within two standard deviations of the Tm for the probe and its homologous virus, the nucleotide sequences of the viruses were considered to be similar. If they were below two standard deviations, they were considered to have one or more nucleotide mutations. The results indicated that the STC and Variant Vax BD viruses have similar genetic sequences at the hydrophilic B region. Likewise, Bursine 2, Bursine, Bursine+, BioBurs, BioBurs W, BioBurs AB, and IBDV Blen have similar nucleotide sequences in this region. The Tm values obtained for the D78 and Del E mutation probes with heterologous viruses indicated that none of the viruses tested had nucleotide sequences that matched these probes. Because the mutation probes were designed to bind to a region that encodes a neutralizing epitope, viruses with similar sequences were expected to have antigenically similar epitopes.


Association between food mixing ability and mandibular movements during chewing of a wax cube.
The purpose of this study was to clarify whether masticatory movements during chewing of a wax cube associate with food mixing ability. Twenty-six dentate subjects (mean age 25.3 years) were directed to chew a two-coloured paraffin wax cube for 10 strokes on preferred chewing side. Mixing Ability Index (MAI) was determined from the colour mixture and shape of the chewed wax cube. MAI was employed as an estimate of food mixing ability. Mandibular movements during chewing of the wax cube were recorded using a six-degrees-of freedom jaw movements recording system, and motion of a lower incisal point of the mandible was computed. Twelve parameters of masticatory movements in relation to mandibular excursion, angle, velocity, cycle duration, duration of each phase were measured for each masticatory cycle. In addition, unilateral maximum biting was performed, and the maximum force during biting was measured using a force-transducer. A multiple regression analysis identified vertical amplitude, closing duration, closing angle and maximum bite force as significant predictors accounting for 63% of inter-subject variation (adjusted R(2)) in the MAI (P < 0.05). Only some parameters of masticatory movements seem to have an influence on the MAI in dentate subjects.


An organic-inorganic perovskite ferroelectric with large piezoelectric response.
Molecular piezoelectrics are highly desirable for their easy and environment-friendly processing, light weight, low processing temperature, and mechanical flexibility. However, although 136 years have passed since the discovery in 1880 of the piezoelectric effect, molecular piezoelectrics with a piezoelectric coefficient d33 comparable with piezoceramics such as barium titanate (BTO; ~190 picocoulombs per newton) have not been found. We show that trimethylchloromethyl ammonium trichloromanganese(II), an organic-inorganic perovskite ferroelectric crystal processed from aqueous solution, has a large d33 of 185 picocoulombs per newton and a high phase-transition temperature of 406 kelvin (K) (16 K above that of BTO). This makes it a competitive candidate for medical, micromechanical, and biomechanical applications.


Loud Noise Exposure Produces DNA, Neurotransmitter and Morphological Damage within Specific Brain Areas.
Exposure to loud noise is a major environmental threat to public health. Loud noise exposure, apart from affecting the inner ear, is deleterious for cardiovascular, endocrine and nervous systems and it is associated with neuropsychiatric disorders. In this study we investigated DNA, neurotransmitters and immune-histochemical alterations induced by exposure to loud noise in three major brain areas (cerebellum, hippocampus, striatum) of Wistar rats. Rats were exposed to loud noise (100 dBA) for 12 h. The effects of noise on DNA integrity in all three brain areas were evaluated by using Comet assay. In parallel studies, brain monoamine levels and morphology of nigrostriatal pathways, hippocampus and cerebellum were analyzed at different time intervals (24 h and 7 days) after noise exposure. Loud noise produced a sudden increase in DNA damage in all the brain areas under investigation. Monoamine levels detected at 7 days following exposure were differently affected depending on the specific brain area. Namely, striatal but not hippocampal dopamine (DA) significantly decreased, whereas hippocampal and cerebellar noradrenaline (NA) was significantly reduced. This is in line with pathological findings within striatum and hippocampus consisting of a decrease in striatal tyrosine hydroxylase (TH) combined with increased Bax and glial fibrillary acidic protein (GFAP). Loud noise exposure lasting 12 h causes immediate DNA, and long-lasting neurotransmitter and immune-histochemical alterations within specific brain areas of the rat. These alterations may suggest an anatomical and functional link to explain the neurobiology of diseases which prevail in human subjects exposed to environmental noise.


Anatomical Study of Chiari Network and the Remnant of Left Venous Valve in the Interior of Right Atrium.
Chiari network occurs due to incomplete resorption of right valve of sinus venosus. It is often noticed as fenestrated membranous structure or reticular network like structure in the valve of inferior vena cava and coronary sinus. The remnant of left venous valve is observed as trabeculae over the fossa ovalis. The incidence of Chiari network and the remnant of left venous valve were studied in 80 cadaveric hearts utilized for teaching the undergraduates. The right atrium was opened anterior to sulcus terminalis and the interior was examined for the presence of these embryological remnants. The incidence of Chiari network and left venous valve in the present study is 3.75% and 7.5%, respectively. Chiari network was observed as a fenestrated membranous structure in 2 specimens and a reticular network in 1 specimen, with variable extension to coronary sinus opening and right atrial wall. The remnant of left venous valve was observed as multiple fine strands in 3 specimens and trabecular structure in 3 specimens. These structures may create diagnostic confusion, difficulty in interventional procedures, and complications like thromboembolic events. Hence, the knowledge about the incidence, morphology, and clinical manifestations of these rare embryological remnants is mandatory.


Inverted papilloma invading the orbit.
Inverted papilloma is an unusual entity for many ophthalmologists. We report a case of inverted papilloma of the nasal cavity and sinuses, invading the orbit in a 33-year-old man. The patient presented with a right medial canthal mass, proptosis, diminution of vision, epiphora and nasal obstruction. In the past, he underwent multiple procedures for surgical removal of the tumor with frequent recurrences. A computed tomographic scan revealed a mass filling both the nasal cavities and sinuses, destroying adjacent bones and invading the medial aspect of the orbit, leading to proptosis. Excision of the tumor was performed by a lateral rhinotomy approach. The tumor proved to be an inverted papilloma with focal transformation to transitional cell carcinoma. Post-operative CT scan revealed residual tumor, which responded to radiotherapy, with no recurrence over six months. Histopathologically, these tumors are benign, but locally invasive. The tumors that invade the orbit are usually locally aggressive, highly malignant and recur frequently. Radical excision of the tumor is technically difficult and often incomplete, so radiotherapy should be considered as an adjunct to surgery.


Adolescent sexual and reproductive health: The global challenges.
Adolescent sexual and reproductive health (ASRH) has been overlooked historically despite the high risks that countries face for its neglect. Some of the challenges faced by adolescents across the world include early pregnancy and parenthood, difficulties accessing contraception and safe abortion, and high rates of HIV and sexually transmitted infections. Various political, economic, and sociocultural factors restrict the delivery of information and services; healthcare workers often act as a barrier to care by failing to provide young people with supportive, nonjudgmental, youth-appropriate services. FIGO has been working with partners and its member associations to break some of these barriers-enabling obstetricians and gynecologists to effect change in their countries and promote the ASRH agenda on a global scale.


Effects of dopamine on endotoxin and hemorrhagic shock in the canine stomach.
Studies were conducted to evaluate the effects of dopamine on gastric electrophysiopathology in endotoxin and hemorrhagic shock. Intraarterial infusion of dopamine (15.5 or 31 microgram/kg/min) in the in vivo stomach preparation produced an immediate decrease in electrical potential difference (PD), which then returned and exceeded control values. No changes in resistance (R) and blood pressure were observed. These electrophysiological responses of the gastric mucosa to dopamine are very similar to the actions of epinephrine. The in vitro studies demonstrated that active transport of Na+ was stimulated with an addition of dopamine or epinephrine (2 X 10(-4) M) to the serosal solutions of the isolated gastric mucosa. In addition, the in vivo studies demonstrated that both 40% hemorrhage and 1 mg/kg of endotoxin given as an intravenous bolus decreased PD and blood pressure and increased R although dopamine was continuously infused intraarterially for 60 minutes prior to and following hemorrhage or endotoxin. Administration of endotoxin at the onset of dopamine infusion decreased both blood pressure and PD initially. While PD showed a complete recovery at a later stage, blood pressure never returned to control levels. These results, combined with previous observations, suggest that: 1) dopamine has no beneficial action on the gastric mucosa during hemorrhagic or endotoxin shock; 2) dopamine acts on the electrophysiology in vivo and Na+ fluxes in vitro in the gastric mucosa in a manner similar to epinephrine; and 3) decrease in blood flow may be responsible for the observed decrease in transmural PD after dopamine and epinephrine in vivo.


Salmonella challenges: prevalence in swine and poultry and potential pathogenicity of such isolates.
Salmonellosis is the second leading cause of bacterial foodborne illness in the United States, and the great majority of these infections are associated with the consumption of products such as meat, poultry, eggs, milk, seafood, and fresh produce contaminated with Salmonella. The per capita consumption of meat and poultry in United States has increased significantly over the past century. This increase is especially evident with poultry products, where there has been a nearly 6-fold increase in chicken consumption and 17-fold increase in turkey consumption since 1909. The per capita consumption of pork has also increased over this time from 18.7 to 21.7 kg/yr. With this increase in meat and poultry consumption, the dynamics of animal production and consumer exposure have changed leading to new challenges in limiting salmonellosis. To meet the demands of consumers, more intensive agricultural practices have been adopted, which has likely changed the population characteristics of Salmonella present among poultry flocks and swine populations. In Salmonella isolated from swine in the United States, S. Typhimurium has replaced S. Choleraesuis as the predominant serovar in recent years. Among isolates from turkeys collected in 2004, serovars S. Senftenberg and S. Hadar were most common overall; however, S. Heidelberg was most common from clinical diagnostic sources, potentially indicating increased virulence. Salmonella Heidelberg was also the most commonly detected serovar among chicken isolates from clinically ill birds and Salmonella surveillance samples. Overall among the 10 serovars most commonly associated with human infections, 6 are also found in the top serovars of swine and poultry. These include S. Typhimurium, S. Enteritidis, S. Heidelberg, S. Montevideo, S. Saintpaul, and S. I 4,[5],12:i:-.


Microglial exosomes facilitate α-synuclein transmission in Parkinson's disease.
Accumulation of neuronal α-synuclein is a prominent feature in Parkinson's disease. More recently, such abnormal protein aggregation has been reported to spread from cell to cell and exosomes are considered as important mediators. The focus of such research, however, has been primarily in neurons. Given the increasing recognition of the importance of non-cell autonomous-mediated neurotoxicity, it is critical to investigate the contribution of glia to α-synuclein aggregation and spread. Microglia are the primary phagocytes in the brain and have been well-documented as inducers of neuroinflammation. How and to what extent microglia and their exosomes impact α-synuclein pathology has not been well delineated. We report here that when treated with human α-synuclein preformed fibrils, exosomes containing α-synuclein released by microglia are fully capable of inducing protein aggregation in the recipient neurons. Additionally, when combined with microglial proinflammatory cytokines, these exosomes further increased protein aggregation in neurons. Inhibition of exosome synthesis in microglia reduced α-synuclein transmission. The in vivo significance of these exosomes was demonstrated by stereotaxic injection of exosomes isolated from α-synuclein preformed fibrils treated microglia into the mouse striatum. Phosphorylated α-synuclein was observed in multiple brain regions consistent with their neuronal connectivity. These animals also exhibited neurodegeneration in the nigrostriatal pathway in a time-dependent manner. Depleting microglia in vivo dramatically suppressed the transmission of α-synuclein after stereotaxic injection of preformed fibrils. Mechanistically, we report here that α-synuclein preformed fibrils impaired autophagy flux by upregulating PELI1, which in turn, resulted in degradation of LAMP2 in activated microglia. More importantly, by purifying microglia/macrophage derived exosomes in the CSF of Parkinson's disease patients, we confirmed the presence of α-synuclein oligomer in CD11b+ exosomes, which were able to induce α-synuclein aggregation in neurons, further supporting the translational aspect of this study. Taken together, our study supports the view that microglial exosomes contribute to the progression of α-synuclein pathology and therefore, they may serve as a promising therapeutic target for Parkinson's disease.