Regulation of Ca2+ uptake in skeletal muscle by 1,25-dihydroxyvitamin D3: role of phosphorylation and calmodulin.
Experiments were carried out to obtain information about the mechanism underlying the fast action of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) in skeletal muscle. N-2'-o-dibutyryladenosine-3',5'-cyclic monophosphate (dbcAMP), similarly as 1,25(OH)2D3 (5 x 10(-10) M), rapidly increased 45Ca uptake by soleus muscle from vitamin D-deficient chicks (+25% and +98% at 3 min and 10 min, respectively) in a dose-dependent manner. The effects of the cAMP analog (10 microM) and 1,25(OH)2D3 could be abolished by the Ca(2+)-channel blocker nifedipine and the calmodulin antagonist flufenazine. Calmodulin binding by two muscle microsomal proteins of 28 kDa and 30 kDa was stimulated within 1 min of exposure of the tissue to 1,25(OH)2D3. Direct effects of the sterol on membrane calmodulin binding were shown with isolated microsomes. The 1,25(OH)2D3-mediated rise of [125I]calmodulin binding to microsomal membranes was dependent on the presence of medium ATP. Forskolin (10 microM) and cAMP (10 microM) also increased [125I]calmodulin binding (+75% and +64%, respectively, with respect to controls). Pretreatment of microsomal membranes with cAMP-dependent protein kinase inhibitor (1 microgram/ml) or addition of alkaline phosphates (1 U/ml) after hormonal treatment caused complete inhibition of 1,25(OH)2D3-induced [125I]calmodulin binding to microsomal membrane proteins. These results imply modifications of membrane protein phosphorylation through the cAMP signal pathway and in turn of calmodulin binding in the mechanism by which 1,25(OH)2D3 rapidly stimulates skeletal muscle Ca2+ uptake.


Ppy/TiO2-SiO2 nanohybrid series: synthesis, characterization, photocatalytic activity, and antimicrobial potentiality.
A series of polypyrrole doped TiO2-SiO2 nanohybrids (Ppy/TS NHs) were synthesized thru in-situ oxidation polymerization by varying weight ratio of pyrrole. The structural analysis of NHs were characterized by X-ray Diffraction (XRD) spectra, UV-visible (UV-Vis) spectra and X-ray Photoelectron spectra (XPS) confirmed synthesis of nanomaterials. Surface and morphological study done by adopting, Scanning Electron Microscopy (SEM), Energy Dispersive Spectroscopy (EDS), Transmittance Electron Microscopy (TEM) and Brunauer-Emmett-Teller (BET) analysis confirmed the homogenous distribution, nano range size formation and mesoporous nature of nanohybrids. Further, electrochemical behavior of synthesized NHs investigated by adopting Electrochemical Impedance Spectroscopy (EIS) showed good kinetic behaviour and electron transport tendency. The nanohybrids and precursors were examined for photocatalytic degradation of methylene blue (MB) dye and revealed enhanced degradation tendency for the NHs series photocatalysts. It was found that variation of pyrrole (0.1 to 0.3 g) to TS nanocomposites (TS Nc) increased the photocatalytic potential of TS Nc. The maximum photodegradation efficacy was found to be 90.48% in 120 min for Ppy/TS0.2 NHs under direct solar light. Additionally, Ppy/TS0.2 NHs performed appreciably towards antibacterial studies against some Gram-positive and Gram-negative deleterious bacteria, Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Shigella flexneri microbes.


In vivo histologic imaging of the muscularis propria and myenteric neurons with probe-based confocal laser endomicroscopy in porcine models (with videos).
The submucosal tunneling technique enables us to endoscopically access deeper tissue layers. Use of probe-based confocal laser endomicroscopy (pCLE) provides optical histologic imaging on the site. To determine the technical feasibility of ex vivo and in vivo pCLE imaging of the muscularis propria and myenteric neurons by using submucosal endoscopy with a mucosal flap safety valve (SEMF). Acute porcine model study. Animal laboratory. Two ex vivo and 6 in vivo porcine models were used. A submucosal space was created with SEMF, and a neuronal molecular probe was topically applied onto the muscularis. Confocal imaging of the stained muscularis was performed by using pCLE. The selected sites were sampled, and the histopathology of the sites was analyzed. The two main outcome measures were the procedural success rate of submucosal access and the correlation between pCLE and histologic images. Submucosal access to the pCLE study site was successful in all attempts (100%; 17/17 sites). The muscularis propria was visualized with pCLE in the ex vivo and in vivo porcine models in 83.3% of sites (20/24), and the neuron-like cells were identified in 41.7% of sites (10/24). Animal experiment. The muscularis propria and myenteric neurons could be selectively visualized with pCLE in vivo.


Unsuccessful Exclusive Breastfeeding and Associated Factors among the Healthcare Providers in East Coast, Malaysia.
Breastfeeding is widely recognized as the optimal and natural method of feeding infants. However, there are obstacles that can limit exclusive breastfeeding practices during the first 6 months of an infant's life. This study aimed to determine the prevalence of unsuccessful exclusive breastfeeding and its associated factors among mothers who work as healthcare providers at Universiti Sains Malaysia Hospital. A cross-sectional study was conducted among 295 medical doctors and staff nurses from June to December 2015. Simple random sampling was applied. The data were collected using a self-administered questionnaire and analyzed using IBM SPSS ver. 22.0 (IBM Corp., Armonk, NY, USA). Descriptive statistics and logistic regression analysis were performed. The prevalence of unsuccessful exclusive breastfeeding among the study participants was 58.3%. Mothers who preferred formula milk (odds ratio [OR], 4.40; 95% confidence interval [CI], 1.45-13.31) delivered via lower segment cesarean section (OR, 2.31; 95% CI, 1.07-4.98) and produced inadequate breast milk (OR, 4.06; 95% CI, 2.40- 6.89) were significantly associated with unsuccessful exclusive breastfeeding. The prevalence of unsuccessful exclusive breastfeeding among the study participants was high. Maternal characteristics such as preference towards formula milk, mode of delivery and adequacy of breast milk must be assessed to prevent unsuccessful exclusive breastfeeding among healthcare providers.


Acetylcholine receptors in human thymic myoid cells in situ: an immunohistological study.
Myoid cells were studied by double immunofluorescence in sections of thymus from 47 patients with myasthenia gravis and 15 control subjects, using polyclonal sheep anti-troponin T and monoclonal antibodies to troponin I, striated muscle myosin, and acetylcholine receptor (AChR). The myoid cells were rare and located mainly in the medulla, and most were clearly positive for AChR; labeling was similar with four individual monoclonal antibodies specific for extrajunctional AChR and five that also recognize endplate AChR. They were mostly keratin-positive and consistently HLA-DR-negative. In the myasthenia gravis samples, the myoid cells were similar but largely confined to medullary epithelial areas; AChR labeling was slightly weaker, but otherwise they did not differ noticeably from those of control subjects. A preliminary finding was of even rarer AChR-positive/HLA-DR-positive antigen-presenting (possibly) cells seen in 9 of 9 myasthenia gravis samples and in none of 9 control samples. Although myoid-cell AChR appears antigenically similar to extrajunctional muscle AChR, and must therefore express the epitopes that myasthenics' antibodies recognize, these cells do not appear to be foci of immunological stimulation in myasthenia gravis.


Pharmacokinetics of hydrochlorothiazide in relation to renal function.
The pharmacokinetics of hydrochlorothiazide (HCT) was investigated in 23 subjects with normal renal function or widely varying degrees of renal failure. The half-life of elimination increased from 6.4 h in subjects with normal renal function to 11.5 h in patients with mild renal impairment (endogenous creatinine clearance between 30 and 90 ml/min), and to 20.7 h in patients with an endogenous creatinine clearance below 30 ml/min. The cumulative urinary excretion and the renal HCT clearance were correspondingly reduced in patients with impaired kidney function. In normal subjects HCT was mainly excreted by tubular secretion, but as renal HCT clearance in patients with renal impairment did not differ significantly from endogenous creatinine clearance, it was concluded that the secretory mechanism is most markedly impaired. In patients with an endogenous creatinine clearance of 30 to 90 ml/min, the dosage of HCT should be reduced to 1/2 and in patients with a endogenous creatinine clearance below 30 ml/min to 1/4 of the normal daily dose to avoid dose dependant side-effects.


Symptomatic Rathke cleft cyst: clinical features and surgical outcomes.
To depict the clinical, operative, and histological features of Rathke cleft cysts (RCCs) in consideration of therapeutic results and recurrence rates. This study included 40 patients (29 female; mean age, 41 years) of symptomatic RCCs with pathological verification. The mean length of follow-up was 76 months. The patients were treated by complete cyst evacuation combined with partial wall excision (7 via craniotomy and 33 transsphenoidally). All subjects were examined neurologically, radiologically, and biochemically to ascertain the clinical significance of surgery on endocrine and visual improvement. Cysts varied in size from 18 to 43 mm (mean, 19.3 mm); 38 (95.0%) had a suprasellar component. Presenting symptoms included headache (75.0%), chiasmopathy (45.0%), and endocrine dysfunction (37.5%). On magnetic resonance imaging, the signal intensities of the cysts were quite variable, with most commonly hyperintensity (75.0%) on T2-weighted and hypointensity (40.0%) on T1-weighted scans, respectively. Cyst contents were found to be mostly mucoid (52.5%) and watery (30.0%). Squamous epithelium was identified in 18 specimens (45.0%). Headaches and visual symptoms resolved or improved in 76.7% and 78.6% of patients, respectively. Hypothyroidism, hypogonadism, growth hormone deficiency, and hypocortisolemia was resolved in 44.4%, 30.0%, 33.3%, and 56.3% of patients, respectively. Two patients (5%) had repeat surgery for symptomatic relapse. Cerebrospinal fluid leakage (2.5%), new hormone deficit (7.5%), and diabetes insipidus (5.0%) were observed after surgery. When RCCs are recognized intraoperatively, the evacuation of their contents and partial cyst obliteration generally afford dramatic improvements in a patient's clinical signs and symptoms, along with low complications and rate of recurrence.


Increasing the metabolic capacity of Escherichia coli for hydrogen production through heterologous expression of the Ralstonia eutropha SH operon.
Fermentative hydrogen production is an attractive means for the sustainable production of this future energy carrier but is hampered by low yields. One possible solution is to create, using metabolic engineering, strains which can bypass the normal metabolic limits to substrate conversion to hydrogen. Escherichia coli can degrade a variety of sugars to hydrogen but can only convert electrons available at the pyruvate node to hydrogen, and is unable to use the electrons available in NADH generated during glycolysis. Here, the heterologous expression of the soluble [NiFe] hydrogenase from Ralstonia eutropha H16 (the SH hydrogenase) was used to demonstrate the introduction of a pathway capable of deriving substantial hydrogen from the NADH generated by fermentation. Successful expression was demonstrated by in vitro assay of enzyme activity. Moreover, expression of SH restored anaerobic growth on glucose to adhE strains, normally blocked for growth due to the inability to re-oxidize NADH. Measurement of in vivo hydrogen production showed that several metabolically engineered strains were capable of using the SH hydrogenase to derive 2 mol H2 per mol of glucose consumed, close to the theoretical maximum. Previous introduction of heterologous [NiFe] hydrogenase in E. coli led to NAD(P)H dependent activity, but hydrogen production levels were very low. Here we have shown for the first time substantial in vivo hydrogen production by a heterologously expressed [NiFe] hydrogenase, the soluble NAD-dependent H2ase of R. eutropha (SH hydrogenase). This hydrogenase was able to couple metabolically generated NADH to hydrogen production, thus rescuing an alcohol dehydrogenase (adhE) mutant. This enlarges the range of metabolism available for hydrogen production, thus potentially opening the door to the creation of greatly improved hydrogen production. Strategies for further increasing yields should revolve around making additional NADH available.


Primary intracardiac leiomyoma arising from cardiomyocyte progenitors at the right ventriculoseptal interface: case report with literature review.
Primary cardiac neoplasms are rare and are usually benign myxomas and rhabdomyomas. Cardiac leiomyomas are usually seen as a part of the spectrum of intravenous leiomyomatosis or benign metastasizing leiomyoma. De novo occurrence of primary intracardiac leiomyomas (PICL) is a rarity. Herein we describe a 14-year-old boy presenting with intermittent dyspnea for 2 years, with a large right ventricular mass suggestive of myxoma on transthoracic echocardiography, without any extracardiac lesions. Histology and immunohistochemistry of the tumor excised under cardiopulmonary bypass confirmed a PICL arising at the cardiomyocyte-smooth muscle septal interface. A review of existing literature highlights an increased incidence in young patients and an overwhelming right ventricular anatomical predilection. Abnormalities in the multipotent cardiac progenitor cells of the second heart field may provide a potential microenvironment for the histogenesis of PICL.


A hierarchical method to automatically encode Chinese diagnoses through semantic similarity estimation.
The accumulation of medical documents in China has rapidly increased in the past years. We focus on developing a method that automatically performs ICD-10 code assignment to Chinese diagnoses from the electronic medical records to support the medical coding process in Chinese hospitals. We propose two encoding methods: one that directly determines the desired code (flat method), and one that hierarchically determines the most suitable code until the desired code is obtained (hierarchical method). Both methods are based on instances from the standard diagnostic library, a gold standard dataset in China. For the first time, semantic similarity estimation between Chinese words are applied in the biomedical domain with the successful implementation of knowledge-based and distributional approaches. Characteristics of the Chinese language are considered in implementing distributional semantics. We test our methods against 16,330 coding instances from our partner hospital. The hierarchical method outperforms the flat method in terms of accuracy and time complexity. Representing distributional semantics using Chinese characters can achieve comparable performance to the use of Chinese words. The diagnoses in the test set can be encoded automatically with micro-averaged precision of 92.57 %, recall of 89.63 %, and F-score of 91.08 %. A sharp decrease in encoding performance is observed without semantic similarity estimation. The hierarchical nature of ICD-10 codes can enhance the performance of the automated code assignment. Semantic similarity estimation is demonstrated indispensable in dealing with Chinese medical text. The proposed method can greatly reduce the workload and improve the efficiency of the code assignment process in Chinese hospitals.


Child sex abuse treatment: some barriers to program operation.
A treatment program for sexually abusing families is described, which illustrates the complexities in the families, in the treatment required to assist them, and in the interrelations of agencies with whom they come into contact. The program used a multi-therapist, multi-modality treatment model in conjunction with expert consultants in medicine, psychology, art therapy, law, criminology, and research. The article discusses the formidable barriers to creating a treatment program that stem from the necessity of establishing linkages with other agencies and systems in the society. These barriers include the difficulty other service providers may have in recognizing the problem; the trouble doctors, lawyers, and policemen have in interviewing the young victims; the problems in the criminal justice system with obtaining justice for the victim by arresting and prosecuting the offender while protecting his rights; and the conflict of the schools caught between their responsibility as mandated reporters of abuse and the legal rights of the parent-offender. Questions are raised which may assist others embarked on developing similar programs.


Validation of analytical methods for ethyl carbamate in nine food matrices.
Ethyl carbamate (EC) is formed through a reaction between ethanol and either cyanate or N-carbamyl compounds. This study aimed to develop and validate analytical methods for EC determination in nine food matrices: apple juice, soju, milk, corn oil, rice porridge, peanut butter, beef, flat fish, and sea mustard. Differences from AOAC procedure were use of d5-EC as internal standard, dilution of alcohol content, removal of lipophilic compounds by hexane, and removal of hydrophilic polysaccharides by gel-forming. Standard curves had a good linearity (R(2)>0.997) in all matrices tested. LOD and LOQ were in the range of 0.69-6.08μg/kg and 2.10-18.43μg/kg, respectively. Recovery rates ranged from 80.75 to 121.82% for intra-day and ranged from 78.84 to 116.98% for inter-day. The relative standard deviations (RSDs) were below 14%. These results indicate that the established methods can be applied to determine EC in a variety of foods.


Identification of a paramagnetic species as an early intermediate in the coenzyme B12-dependent glutamate mutase reaction. A cob(II)amide?
Highly active and cobamide-free glutamate mutase was obtained from Clostridium cochlearium by a modification of the original purification procedure. After incubation of the enzyme with dithiothreitol, adenosylcobalamin (coenzyme B12) and the substrate (S)-glutamate, a paramagnetic species was observed by EPR-spectroscopy. The signal was maximal within 15 ms after mixing with glutamate. Different signals were detected after incubating the system with the competitive inhibitors (2S,4S)-4-fluoroglutamate or 2-methyleneglutarate instead of the substrate. The former developed with an at least 100-fold lower rate then the signal with glutamate. All three signals are probably due to low-spin cob(II)amide species with an extraordinary low gxy value as compared with cob(II)alamin.


The detection of Clostridium perfringens epsilon antitoxin in rabbit serum by monoclonal antibody based competition ELISA.
A competitive enzyme-linked immunosorbent assay (CELISA) has been developed, standardized and compared with the toxin neutralization (TN) test performed in mice for the measurement of antibody responses in rabbits vaccinated with clostridial vaccines. In CELISA, sera were tested at a single dilution for their ability to compete with the reaction between a monoclonal antibody, which neutralizes epsilon toxin, and epsilon toxoid coated on to a solid phase. The results of the two tests correlated well. CELISA was specific, rapid, reproducible and simple to perform and offered an alternative to the TN test that reduced the requirement for experimental animals in the potency testing of clostridial vaccines.


Insight Into Kidney Protection by Vacuum-Assisted Venous Drainage in Adult Cardiac Operation - A Multicenter Study.
The relationship between venous congestion and acute kidney injury (AKI) in cardiac surgery after cardiopulmonary bypass has not thoroughly investigated. Vacuum-assisted venous drainage (VAVD) reduces venous congestion, so we hypothesized that it would reduce the incidence of AKI in cardiovascular surgery.Methods and Results: We used a retrospective propensity score-matched analysis to evaluate the effect of VAVD on AKI in adult patients undergoing cardiac surgery. The primary outcomes were AKI and renal replacement therapy (RRT). Multivariable logistic regression was used to explore the association between VAVD exposure and adverse kidney outcomes. Of 15,387 eligible subjects, 13,480 and 1,907 had gravity drainage (GD) or VAVD, respectively, during cardiopulmonary bypass. On the basis of propensity scores, there were 1,468 matched patient pairs for GD and VAVD. The average central venous pressure (CVP) in the GD group was higher than in the VAVD group (4.43±1.23 mmHg vs. 2.30±0.98 mmHg, P<0.001). The occurrence of AKI and RRT was statistically significantly different in the 2 groups [(600/1,468, 40.87%) vs. (445/1,468, 30.31%), P<0.001; (36/1,468, 2.45% vs. 8/1,468; 0.54%), P<0.001, respectively)]. Multivariate logistic regression analysis revealed that VAVD was effective in protecting kidney function. VAVD was associated with a lower CVP and lower incidence of AKI, suggesting it protects adult cardiac patients from adverse renal outcomes.


Soil CO2 and CH4 fluxes from different forest types in tropical peat swamp forest.
Information on temporal and spatial variations in soil greenhouse gas (GHG) fluxes from tropical peat forests is essential to predict the influence of climate change and estimate the effects of land use on global warming and the carbon (C) cycle. To obtain such basic information, soil carbon dioxide (CO2) and methane (CH4) fluxes, together with soil physicochemical properties and environmental variables, were measured at three major forest types in the Maludam National Park, Sarawak, Malaysia, for eight years, and their relationships were analyzed. Annual soil CO2 fluxes ranged from 860 to 1450 g C m⁻2 yr⁻1 without overall significant differences between the three forest sites, while soil CH4 fluxes, 1.2-10.8 g C m⁻2 yr⁻1, differed. Differences in GHG fluxes between dry and rainy seasons were not necessarily significant, corresponding to the extent of seasonal variation in groundwater level (GWL). The lack of significant differences in soil CO2 fluxes between the three sites could be attributed to set-off between the negative and positive effects of the decomposability of soil organic matter as estimated by pyrophosphate solubility index (PSI) and GWL. The impact of El-Niño on annual CO2 flux also varied between the sites. The variation in soil CH4 fluxes from the three sites was enhanced by variations in temperature, GWL, PSI, and soil iron (Fe) content. A positive correlation was observed between the annual CH4 flux and GWL at only one site, and the influence of soil properties was more pronounced at the site with the lowest GWL and the highest PSI. Variation in annual CH4 fluxes was controlled more strongly by temperature where GWL was the highest and GWL and plant growth fluctuations were the least. Inter-annual variations in soil CO2 and CH4 fluxes confirmed the importance of long-term monitoring of these at multiple sites supporting different forest types.


Expression analysis in a rat psychosis model identifies novel candidate genes validated in a large case-control sample of schizophrenia.
Antagonists of the N-methyl-D-aspartate (NMDA)-type glutamate receptor induce psychosis in healthy individuals and exacerbate schizophrenia symptoms in patients. In this study we have produced an animal model of NMDA receptor hypofunction by chronically treating rats with low doses of the NMDA receptor antagonist MK-801. Subsequently, we performed an expression study and identified 20 genes showing altered expression in the brain of these rats compared with untreated animals. We then explored whether the human orthologs of these genes are associated with schizophrenia in the largest schizophrenia genome-wide association study published to date, and found evidence for association for 4 out of the 20 genes: SF3B1, FOXP1, DLG2 and VGLL4. Interestingly, three of these genes, FOXP1, SF3B1 and DLG2, have previously been implicated in neurodevelopmental disorders.


Pattern and mortality in Colorado Desert plants.
We tested for intraspecific interference among Colorado Desert shrubs using an integrated analysis of spatial pattern and juvenile mortality. The data set included 7,000 woody perennials of 24 species in a mapped hectare of Joshua Tree National Monument, California. The site is dominated by Ambrosia dumosa (62.0% of the stems), with Larre tridentata a conspicuous secondary species (2.3% of the stems). Analyses of static pattern for common species showed: (1) aggregated adults and juveniles for Ambrosia dumosa, Erigonum fasciculatum, Mirabilis bigelovii, and Sphaeralcea ambigua, with more aggregation among juveniles than adults; (2) randomly distributed adults and juveniles for Krameria grayi, Opuntia rasmosissima, Simondsia chinensis, and Yucca schidigera. The summed volumes and distances between nearest conspecific neighbors were positively correlated for Ambrosia dumosa and Larrea tridentata, but not significantly correlated for eight remaining species with ≥100 individuals. Static pattern suggests only weak evidence for negative interactions in Ambrosia and Larrea, and little evidence for other species. Alternative mechanisms other than negative interaction that could give rise to these static patterns are discussed. Juvenile mortality was documented for four common species (Ambrosia dumosa, Eriogonum fasciculatum, Mirabilis bigelovii, and Sphaeralcea ambigua) that experienced substantial mortality. Analyses show: (1) the proportion of individuals that died was independent of the initial density of conspecifics; (2) distance to conspecific adults did not differ for juveniles that died versus those that survived; and (3) death was no more likely for juveniles that contacted other plants than for those that were isolated. The exception was a vine, Mirabilis bigelovii, whose juveniles survived better in contact with other plants. In sum, neither spatial pattern nor patterns of mortality showed clear evidence of negative intraspecific interference.


[Iatrogenic skin-tissue embolism in the lung].
A rare autopsy finding of an embolic fragment of skin in the lung after intravenous injection and central venous catheterization is described. Frequency, origin and fate of these microembolisms are discussed.


Influence of the physical properties of the layered oxyselenides Bi2YO4Cu2Se2 through Ni doping.
We have synthesized a series of Ni-doped layered oxyselenides Bi2YO4Cu2-xNixSe2 (0 ≤ x ≤ 0.4). The crystal structure and physical properties were studied through X-ray diffraction, and electric and thermo transport measurements. We also performed DFT calculations to study the electric structure of the designed Bi2YO4Ni2Se2, which is similar to that of KNi2Se2.


Directed attention prolongs the perceived duration of a brief stimulus.
Stelmach, Herdman, and McNeil (1994) suggested recently that the perceived duration for attended stimuli is shorter than that for unattended ones. In contrast, the attenuation hypothesis (Thomas & Weaver, 1975) suggests the reverse relation between directed attention and perceived duration. We conducted six experiments to test the validity of the two contradictory hypotheses. In all the experiments, attention was directed to one of two possible stimulus sources. Experiments 1 and 2 employed stimulus durations from 70 to 270 msec. A stimulus appeared in either the visual or the auditory modality. Stimuli in the attended modality were rated as longer than stimuli in the unattended modality. Experiment 3 replicated this finding using a different psychophysical procedure. Experiments 4-6 showed that the finding applies not only to stimuli from different sensory modalities but also to stimuli appearing at different locations within the visual field. The results of all six experiments support the assumption that directed attention prolongs the perceived duration of a stimulus.


The clinical impact of observer variability in lung nodule classification in children with Wilms tumour.
To investigate the extent to which observer variability of computed tomography (CT) lung nodule assessment may affect clinical treatment stratification in Wilms tumour (WT) patients, according to the recent Société Internationale d'Oncologie Pédiatrique Renal Tumour Study Group (SIOP-RTSG) UMBRELLA protocol. I: CT thoraces of children with WT submitted for central review were used to estimate size distribution of lung metastases. II: Scans were selected for blinded review by five radiologists to determine intra- and inter-observer variability. They assessed identical scans on two occasions 6 months apart. III: Monte Carlo simulation (MCMC) was used to predict the clinical impact of observer variation when applying the UMBRELLA protocol size criteria. Lung nodules were found in 84 out of 360 (23%) children with WT. For 21 identified lung nodules, inter-observer limits of agreement (LOA) for the five readers were ±2.4 and ±1.4 mm (AP diameter), ±1.9 and ±1.8 mm (TS diameter) and ±2.0 and ±2.4 mm (LS diameter) at assessments 1 and 2. Intra-observer LOA across the three dimensions were ±1.5, ±2.2, ±3.5, ±3.1 and ±2.6 mm (readers 1-5). MCMC demonstrated that 17% of the patients with a 'true' nodule size of ≥3 mm will be scored as <3 mm, and 21% of the patients with a 'true' nodule size of <3 mm will be scored as being ≥3 mm. A significant intra-inter observer variation was found when measuring lung nodules on CT for patients with WT. This may have significant implications on treatment stratification, and thereby outcome, when applying a threshold of ≥3 mm for a lung nodule to dictate metastatic status.


Inflammatory cytokines and chemokines in obese adolescents with antibody against to adenovirus 36.
Obesity in adolescents has reached epidemic proportions and is associated with the inflammatory response and viral infections. The aim of this study was to understand the profile of inflammatory cytokines and chemokines associated with the inflammatory response and metabolic syndrome (MetS) in obese adolescents with positive serology for adenovirus 36 (ADV36). Thirty-six overweight, 36 obese, and 25 severe obesity adolescents aged 10 to 16 years were included in the study. The following variables were analyzed: sex, age, body mass index (BMI), blood pressure, total cholesterol and fractions, triglycerides, glucose, serum cytokine concentrations, and ADV36 antibodies. Cytokines and chemokines were quantified by cytometry and ADV36 serology was determined by enzyme-linked immunosorbent assay (ELISA). The results showed higher levels of the cytokines interleukin-1beta (IL-1β), IL-6, IL-10 and of the chemokine interferon-gamma-inducible protein 10 (IP-10) in severe obesity adolescents compared to the obese and overweight groups, as well as in the group with MetS compared to the group without this syndrome. The frequency of ADV36-positive individuals did not differ between groups. The findings revealed differences in BMI between the obese and severe obesity groups versus the overweight group in the presence of positivity for ADV36, suggesting an association with weight gain and possibly MetS installation.


Matrix metalloproteinase, tissue inhibitor of metalloproteinase and transforming growth factor-beta 1 in frozen shoulder, and their changes as response to intensive stretching and supervised neglect exercise.
Frozen shoulder is characterized with thickening and contracture of joint capsular. The mechanism of this disorder is not yet clear, however, some proteins have been related to frozen shoulder. This study was to compare the serum levels of proteins related to frozen shoulder, such as matrix metalloproteinase (MMP), tissue inhibitor of metalloproteinase (TIMP) and transforming growth factor-beta (TGF-β) between frozen shoulder and normal subjects; and before and after physical exercise active stretching and gentle thawing in frozen shoulder patients. Serum levels of MMP-1, MMP-2, TIMP-1, TIMP-2, and TGF-β1 was measured from frozen shoulder and normal subjects by using ELISA. Functional assessment of shoulder joint in frozen shoulder patients was based on abbreviated Constant score. Frozen shoulder patients were randomly divided into intensive stretching and supervised neglect groups. Abbreviated Constant score and serum samples of frozen shoulder patients were evaluated at baseline, week-6, and week-12 after exercise, while only baseline serum samples of control were measured. MMP/TIMP ratio was calculated from the total sum of MMP-1 and MMP-2 levels divided by the total sum of TIMP-1 and TIMP-2 levels. Baseline MMP-1 and MMP-2 levels were significantly lower, while TIMP-1, TIMP-2, and TGF-β1 levels were significantly higher in frozen shoulder group than in control. Increased MMPs and decreased TIMPs were significantly greater after intensive stretching than after supervised neglect exercise. Abbreviated Constant score improvement was significantly higher in intensive stretching group than in supervised neglect group. Serum levels of MMP-1, MMP-2, TIMP-1, TIMP-2, and TGF-β1 may be associated to frozen shoulder. Active stretching can improve frozen shoulder better than supervised neglect, as demonstrated by the improvement of Constant score.


Increased 68 Ga-FAPI Uptake in Benign Metastasizing Leiomyoma.
Benign metastasizing leiomyomas (BMLs) are benign disseminated extrauterine tumors in patients with prior history of uterine leiomyomas and may occur years after hysterectomy. In this case, we presented 18 F-FDG and 68 Ga-FAPI PET/CT findings in a 37-year-old woman with benign leiomyoma metastasizing to lung and pelvis. The metastatic lesions demonstrated faint 18 F-FDG but elevated 68 Ga-FAPI activity, indicating the low level of glucose metabolism but excessive accumulation of activated fibroblasts in the BMLs. This case demonstrated that 68 Ga-FAPI PET/CT may be potentially useful in the evaluation of BMLs.


Pulmonary manifestations of the rheumatic diseases.
The collagen vascular diseases represent a heterogeneous group of multisystem disorders with a wide range of clinicopathologic features. Although these diseases represent distinct clinical entities, a great deal of overlap exists between them. For example, the diffuse interstitial fibrosis of SLE, RA, DM-PM, PSS, and MCTD are indistinguishable clinically, radiographically, and histologically. Conversely, the pulmonary manifestations of the various vasculitides all differ significantly from each other in their clinicopathologic presentation, as well as in their response to therapy. For diagnostic purposes, histologic evidence will usually be required for the pulmonary manifestations of the rheumatic diseases. Therapy must then be individualized for each of these entities, as the protocol and response are variable.


Basal epithelial formalin pigment deposition in the kidneys--a useful marker for ketoacidosis at autopsy.
Basal vacuolization of renal epithelial cells occurs in diabetic and alcoholic ketoacidosis, hypothermia and starvation. The vacuoles contain triglycerides. Following a case where formalin pigment deposition within these vacuoles led to the identification of ketoacidosis, a retrospective review of a further 31 cases with ketoacidosis, was undertaken. There were 24 diabetics and 7 alcoholics (age range 21-80 yrs; mean 50.9 yrs; M:F ratio = 2:1. The post-mortem interval was 1-12 days (mean - 4.5 days). Characteristic basally-located pigment surrounding vacuoles was found in 16 cases (51.6%) (14 diabetic ketoacidosis; 2 alcoholic ketoacidosis). Fifteen cases had no formalin pigment deposition. No relationship could be found between the intensity of staining and the postmortem interval, degree of putrefaction, or level of vitreous humour β-hydroxybutyrate. No staining was demonstrated in control cases matched for postmortem interval. Although formalin pigment deposition occurred in only 51.6% of cases with proven ketoacidosis at autopsy, it appeared to be a highly specific phenomenon. As these deposits were identifiable after recognizable cellular morphology had been lost due to autolysis and putrefaction, this artefact of fixation may be of particular use in suggesting the possibility of ketoacidosis in decomposed bodies with compromised histology.


Using Spinal Anesthesia and a Fracture Table for Closed Reduction of an Obturator Foramen Hip Dislocation: A Case Report.
A 37-year-old man with a right obturator foramen hip dislocation underwent closed reduction under spinal anesthesia with the use of a fracture traction table. This novel technique provides surgeons and anesthesiologists an alternative method of treating obturator foramen hip dislocations that provides a more controlled reduction and less need for assistants.


Chronic implanting of electrodes in the cerebellar vermis of the cat. Morphological findings.
The morphological modifications of the cerebellar cortex have been evaluated in eight cats with chronic electrodes implanted in the anterior vermis. In a control animal a silastic lamina without electrodes was implanted. Four animals received intermittent stimulations up to 11 hours in one case and 100 hours in the other 3. The stimulation was carried out with pulses of 0.5 msc, 200 cps, and a charge per phase of 0.68 muc. Microscopic examination of the cerebellum showed that the experimental implanting of prostheses of the cerebellar vermis produces tissue lesions consisting of fibrous reaction, imprinting of the cortex, gliosis, and loss of Purkinje cells. These lesions are independent of the electric stimulation, and seem to be related to the pressure of foreign material against the cortex.


Fulminant leukemoid reaction due to postpartum Clostridium sordellii infection.
Clostridium sordellii is gram positive anaerobic spore forming rod and it has been demonstrated to cause gas gangrene, refractory shock, leukemoid reaction, and pleuroperitoneal effusion due to capillary leak. We report here a case of postpartum female who presented with leukemoid reaction, ascites, pleural effusion, and shock without fever 7 days after normal vaginal home delivery.


Selection of reliable reference genes for RT-qPCR studies in Octopus vulgaris paralarvae during development and immune-stimulation.
The common octopus, Octopus vulgaris is a new candidate species for aquaculture. However, rearing of octopus paralarvae is hampered by high mortality and poor growth rates that impede its entire culture. The study of genes involved in the octopus development and immune response capability could help to understand the key of paralarvae survival and thus, to complete the octopus life cycle. Quantitative real-time PCR (RT-qPCR) is the most frequently tool used to quantify the gene expression because of specificity and sensitivity. However, reliability of RT-qPCR requires the selection of appropriate normalization genes whose expression must be stable across the different experimental conditions of the study. Hence, the aim of the present work is to evaluate the stability of six candidate genes: β-actin (ACT), elongation factor 1-α (EF), ubiquitin (UBI), β-tubulin (TUB), glyceraldehyde 3-phosphate dehydrogenase (GADPH) and ribosomal RNA 18 (18S) in order to select the best reference gene. The stability of gene expression was analyzed using geNorm, NormFinder and Bestkeeper, in octopus paralarvae of seven developmental stages (embryo, paralarvae of 0, 10, 15, 20, 30 and 34days) and paralarvae of 20days after challenge with Vibrio lentus and Vibrio splendidus. The results were validated by measuring the expression of PGRP, a stimuli-specific gene. Our results showed UBI, EF and 18S as the most suitable reference genes during development of octopus paralarvae, and UBI, ACT and 18S for bacterial infection. These results provide a basis for further studies exploring molecular mechanism of their development and innate immune defense.


The effect of CO2 pneumovesicum on upper urinary tract.
Pneumovesicum allows minimal invasive intravesical surgeries. The possible deleterious effect of intravesical CO(2) pressure is not known. We assessed the effect of CO(2) pneumovesicum on the urinary tract and renal function. Pneumovesicum was established and maintained with CO(2) at 10 mm Hg in 10 sows. Cohen cross-trigonal reimplantation was carried out on the left ureter by a vesicoscopic approach. The right ureter was cannulated and served as control. CO(2) pneumovesicum was maintained for 2 hours. Color Doppler measurements of the upper urinary tract and blood sampling were carried out 30 minutes before and 2 hours after establishing pneumovesicum, and 30 minutes after releasing the pneumovesicum. Compared with the preoperative values, the bilateral anteroposterior diameters of the renal pelves increased significantly after 2 hours of the pneumovesicum (P < .05). Thirty minutes after release of the pneumovesicum, the anteroposterior diameters decreased and showed no statistically significant difference compared with the preoperative values. No air embolus was detected in the ureters, renal pelves, renal veins, or renal arteries on either side 2 hours after establishing the pneumovesicum. There was no statistically significant change in arterial or venous blood flow. There was no significant change in the urea and creatinine levels 2 hours after establishing the pneumovesicum. CO(2) pneumovesicum at a pressure of 10 mm Hg for 2 hours did not result in any demonstrable deleterious effect.


Influence of age and gender on gastric acid secretion as estimated by integrated acidity in patients referred for 24-hour ambulatory pH monitoring.
Earlier studies have suggested that gastric acid secretion declines with age. Integrated acidity (IA) calculated from ambulatory 24-h pH studies provides an estimation of gastric acid secretion that is less cumbersome than nasogastric aspiration. The aim of this study was to calculate IA as a function of age and gender. In a retrospective study, 753 ambulatory 24-h pH studies from 1994 to 2001 were analyzed. Subjects were classified according to nine age groups: <35 yr (n = 124), 35-39 yr (n = 90), 40-44 yr (n = 92), 45-49 yr (n = 111), 50-54 yr (n = 96), 55-59 yr (n = 61), 60-64 yr (n = 59), 65-69 yr (n = 42), and > or =70 yr (n = 64). Basal integrated acidity (BIA) was defined as IA between 12 midnight and 8 AM when no meals were consumed. Daytime and nocturnal IA/h was measured from 8 AM to 8 PM and from 8 PM to 8 AM. Postprandial IA (PIA) was measured for 2 h after the largest meal peak in each patient. Gender distribution was similar between groups (chi(2) = 6.42, 3 df, p = 0.093). Mean gastric pH was similar between genders (2.96 +/- 1.36 women; 3.01 +/- 1.42 men; p = 0.71). Women and men had similar BIA (361.1 +/- 384.1 vs 434.6 +/- 436.6 mmol/L/h, p = 0.10), daytime IA (33.5 +/- 33.0 vs 34.1 +/- 33.7 mmol/L, p = 0.90) and nocturnal IA (43.3 +/- 42.1 vs 48.0 +/- 46.6 mmol/L, p = 0.42), and PIA (38.2 +/- 58.7 vs 36.0 +/- 58.5 mmol/L/h, p = 0.47). Mean gastric pH, daytime and nocturnal IA, BIA, and PIA did not differ between age groups (p > 0.1). None of the parameters studied had a linear association with age (mean gastric pH, r = 0.106; BIA, r = -0.124; daytime IA, r = -0.046; nocturnal IA, r = -0.104; PIA, r = -0.117). Based on this study, we conclude that IA is unaffected by gender or age.


Antenatal depression and adversity in urban South Africa.
In low and middle-income countries (LMIC), common mental disorders affecting pregnant women receive low priority, despite their disabling effect on maternal functioning and negative impact on child health and development. We investigated the prevalence of risk factors for antenatal depression among women living in adversity in a low-resource, urban setting in Cape Town, South Africa. The MINI Neuropsychiatric Interview (MINI Plus) was used to measure the diagnostic prevalence of depression amongst women attending their first antenatal visit at a primary-level, community-based clinic. Demographic data were collected followed by administration of questionnaires to measure psychosocial risk. Analysis examined the association between diagnosis of depression and psychosocial risk variables, and logistic regression was used to investigate predictors for major depressive episode (MDE). Among 376 women participating, the mean age was 26 years. The MINI-defined prevalence of MDE was 22%, with 50% of depressed women also expressing suicidality. MDE diagnosis was significantly associated with multiple socioeconomic and psychosocial risk factors, including a history of depression or anxiety, food insecurity, experience of threatening life events and perceived support from family. The use of self-report measures may have led to recall bias. Retrospective collection of clinical data limited our ability to examine some known risk factors for mental distress. These findings confirm the high prevalence of MDE among pregnant women in LMIC settings. Rates of depression may be increased in settings where women are exposed to multiple risks. These risk factors should be considered when planning maternal mental health interventions.


Changes in all-cause and cardiovascular disease mortality in three different Finnish population cohorts with and without diabetes.
We aimed to assess changes in cardiovascular (CVD) and all-cause mortality among diabetic and non-diabetic individuals between three large study cohorts with baseline assessments of 10 years apart and followed up for 10 years. Six population surveys were carried out in 1972, 1977, 1982, 1987, 1992 and 1997 in Finland. For the analyses we combined the 1972 and 1977 cohorts (cohort 1), the 1982 and 1987 cohorts (cohort 2) and similarly also the 1992 and 1997 cohorts (cohort 3). Age-adjusted hazard ratio (HR) of all-cause mortality and CVD in men without diabetes showed that both had a statistically significant decreased risk of all-cause mortality compared to the first cohort. No statistically significant changes in all-cause mortality were observed in men and women with diabetes between the latter two cohorts compared with the first after controlling for several covariates. In both men and women without diabetes, cohort 2 (men, HR=0.65; 95% CI 0.51-0.82; women, HR=0.54; 95% CI 0.32-0.89) and cohort 3 (men, HR=0.32; 95% CI 0.22-0.47; women, HR=0.31; 95% CI 0.14-0.68) showed a statistically significant decreased risk of CVD mortality compared to cohort 1. Age-adjusted HRs in regard to CVD mortality in men (HR=0.22; 95% CI 0.07-0.69) and women (HR=0.22; 95% CI 0.05-0.99) with diabetes of cohort 3 were statistically significantly lower than in cohort 1. There seems to be a decrease in CVD mortality in people with diabetes indicating that treatment of diabetes and cardiovascular risk factors in diabetes patients may have improved during the last decade.


Bloodletting at Jing-well points decreases interstitial fluid flow in the thalamus of rats.
To investigate the changes in the neuronal microenvironment of the middle cerebral artery (MCA) territory induced by Jing-well points bloodletting acupuncture (WPBA) and to explore the neuroprotective mechanism of WPBA in stroke. Adult male Sprague Dawley (n = 32) rats were randomly divided into four groups of eight animals each: WPBA-thalamus group (WT), WPBA-caudate nucleus group (WC), sham-control thalamus group (ST) and sham-control caudate nucleus group (SC). Animals in the WT and WC groups received 2 µL of the extracellular tracer gadolinium-diethylene triamine pentaacetic acid (Gd-DTPA) injected into the thalamus or caudate nucleus, respectively, and 12 Jing-well points in the distal ends of the rats' digits were used for WPBA. Although 2 µL of Gd-DTPA was injected into the thalamus or caudate nucleus, respectively, for animals in the two sham groups (ST and SC), no acupuncture or bloodletting was performed. Brain extracellular space and interstitial fluid flow parameters were measured using Gd-DTPA-enhanced magnetic resonance imaging. The brain interstitial fluid flow speed was decreased in the thalamus after WPBA, with a significantly lower Gd-DTPA clearance rate and longer half-life of Gd-DTPA in the thalamus of treated rats than those in sham-control rats [WPBA-treated rats' clearance rate, (7.47 ± 3.15) x 10(-5)/s (P.= 0.009); half-life, (1.52 ± 0.13) h, P = 0.000]. By contrast, no significant changes in brain extracellular space and interstitial fluid flow parameters were detected in the caudate nucleus after WPBA (P = 0.649). In addition, no differences in the morphology of the brain extracellular space or the final distribution of the traced brain interstitial fluid were demonstrated between the WT and WC groups (P = 0.631, P = 0.970, respectively). The WPBA decreased the speed of the local thalamic ISF flow in rats, which is assumed to be a beneficial protection by down-modulated the metabolic rate of the attacked neurons under stroke.


Hemodynamic Effects of Ultrasound-Assisted, Catheter-Directed, Very Low-Dose, Short-Time Duration Thrombolysis in Acute Intermediate-High Risk Pulmonary Embolism (from the EKOS-PL Study).
Ultrasound-assisted, catheter-directed, low-dose thrombolysis (USAT) at an average alteplase dose of 20 mg infused over 12 to 24 hours reversed right ventricular disfunction and improved pulmonary hemodynamics in intermediate-high-risk pulmonary embolism patients. As bleeding risk increases with the thrombolytic dose, establishing a minimal effective USAT dosing regimen is of clinical importance. We aimed to investigate hemodynamic effects and safety of a very low-alteplase-dose USAT of 10 mg administered within 5 hours. We included 12 consecutive intermediate-high-risk pulmonary embolism patients with symptoms duration of <14 days and proximal thrombi location in pulmonary arteries. Pulmonary Embolism Response Team decision-based fixed, bilateral ultrasound-assisted alteplase infusions at the rate of 1mg/hour/catheter for 5 hours through EKOS system catheters were made. The primary efficacy measure was the change in invasive systolic and mean pulmonary arteries pressure, and in cardiac index from USAT start to termination. Safety measures were 180-day all-cause death or cardiopulmonary decompensation and bleeding complications. The systolic pulmonary arteries pressure and mean pulmonary arteries pressure decreased from 53 (45.5 to 59) to 37.5 (27.5 to 40.5) mm Hg (p = 0.02) and from 29.5 (27.5 to 32) to 21.5 (15.5 to 25) mm Hg (p = 0.02), respectively. The cardiac index increased from 1.6 (1.5 to 1.8) to 2.2 (1.9 to 2.4) l/min/m2, (p = 0.02). No deaths, decompensations, or need for therapy intensification occurred. There was 1 episode of access-site bleeding, which subsided after conservative management. No intracranial hemorrhages appeared. In conclusion, reduced dose and duration USAT improved pulmonary hemodynamics and cardiac function leading to cardiopulmonary stabilization in intermediate-high risk pulmonary embolism patients at a low periprocedural risk.


Determination of trace bisphenols in functional beverages through the magnetic solid-phase extraction with MOF-COF composite.
In this study, a novel porous composite (Fe3O4@TAPB-COF@ZIF-8) consisting of metal-organic and covalent organic frameworks was developed and applied to the magnetic solid-phase extraction (MSPE) of bisphenols. The extraction parameters such as the extraction time, solution pH, amounts of adsorbent, and ionic strength were investigated to obtain the best extraction conditions. By optimizing the MSPE, a convenient and sensitive analytical method was established in combination with high-performance liquid chromatography. The method achieved low detection limits (0.04-0.05 ng mL-1), wide linear range (0.25-1000 ng mL-1), good repeatability (1.20-4.30%), good reproducibility (1.34-4.03%), and satisfactory recoveries of four functional beverages (66.2-116.6%).


A comparative study of 3 surgical methods for hysterectomy with staging for endometrial cancer: robotic assistance, laparoscopy, laparotomy.
The purpose of this study was to compare outcomes in women who underwent endometrial cancer staging by different surgical techniques. Three hundred twenty-two women underwent endometrial cancer staging: 138 by laparotomy (TAH); 81 by laparoscopy (TLH) and 103 by robotic technique (TRH). The TRH cohort had a higher body mass index than the TLH cohort (P = .0008). Lymph node yield was highest for TRH (P < .0001); hospital stay (P < .0001) and estimated blood loss (P < .0001) were lowest for this cohort. Operative time was longest for TLH (213.4 minutes) followed by TRH (191.2 minutes) and TAH (146.5 minutes; P < .0001. Postoperative complication rates were lower for TRH, compared with TAH (5.9% vs 29.7%; P < .0001). Conversion rates for the robotic and laparoscopic groups were similar. TRH with staging is feasible and preferable over TAH and may be preferable over TLH in women with endometrial cancer. Further study is necessary to determine long-term oncologic outcomes.


Study of the placental transfer of cisapride in sheep. Plasma levels in the pregnant ewe, the fetus, and the lamb.
The placental transfer of cisapride, a new prokinetic agent, was studied in a sheep model. The pharmacokinetics of cisapride were studied in the lamb, the pregnant ewe, and the fetus by obtaining blood samples from chronically implanted arterial catheters. Comparable pharmacokinetic parameters were found in the lamb and the adult sheep: half-life, 1.39-1.83 hr; total plasma clearance, 1998-2160 ml/kg/hr; AUC, 92.6-100.1 ng.hr/ml. Cisapride plasma concentrations after continuous infusion were predicted correctly based on the parameters obtained after iv bolus. There was a materno-fetal transfer of cisapride following a single iv bolus administered to the mother. Cisapride crossed the placenta within 5 min and equilibrated with maternal plasma within 20 to 30 min after dosing. The average fetal-to-maternal plasma concentration ratio was 0.71. The amniotic fluid also contained measurable amounts of cisapride. The protein binding of cisapride in maternal and fetal plasma is 89.0% and 88.4%, respectively; the free fraction is 4 times larger than in humans. Cisapride crosses the ovine placental barrier. The sheep placenta is less permeable than the human placenta, but the higher free fraction of cisapride facilitates placental transfer.


Valve replacement in the octogenarian.
Twenty-five patients (11 men and 14 women) aged 80 to 88 years (mean age, 82 years) underwent valve replacement at St. Louis University from August 1980 to June 1988. Isolated valve replacement was performed in 11 patients. Combined procedures included valve replacement with myocardial revascularization (7 patients), multiple valve procedures (5 patients), and ascending aortic plication (2 patients). Fifteen patients (60%) were in New York Heart Association functional class III and 10 (40%) were in class IV preoperatively. The operative mortality was 20% and late mortality was 20% (mean follow-up, 36 months). Isolated valve replacement carried a 9% early and 0% late mortality, whereas combined procedures of any type had a 16% early and 20% late mortality. Only 7 patients (28%) had a completely uncomplicated postoperative hospitalization. Twenty patients were discharged after a mean hospital stay of 18 +/- 16 days. Their mean New York Heart Association functional class was 1.6 +/- 0.66. The 1-year and 2-year actuarial survival rate is 79% and 69%, respectively. A significant increase in operative mortality is seen when valve replacement is combined with myocardial revascularization or an additional valve procedure. Late clinical improvement, as judged by return to an independent life-style, justifies this approach for select patients.


Fast microwave-assisted preparation of a low-cost and recyclable carboxyl modified lignocellulose-biomass jute fiber for enhanced heavy metal removal from water.
A low-cost and recyclable biosorbent derived from jute fiber was developed for high efficient adsorption of Pb(II), Cd(II) and Cu(II) from water. The jute fiber was rapidly pretreated and grafted with metal binding groups (COOH) under microwave heating (MH). The adsorption behavior of carboxyl-modified jute fiber under MH treatment (CMJFMH) toward heavy metal ions followed Langmuir isotherm model (R(2)>0.99) with remarkably high adsorption capacity (157.21, 88.98 and 43.98mg/g for Pb(II), Cd(II) and Cu(II), respectively). Also, CMJFMH showed fast removal ability for heavy metals in a highly significant correlation with pseudo second-order kinetics model. Besides, CMJFMH can be easily regenerated with EDTA-2Na solution and reused up to at least four times with equivalent high adsorption capacity. Overall, cheap and abundant production, rapid and facile preparation, fast and efficient adsorption of heavy metals and high regeneration ability can make the CMJFMH a preferred biosorbent for heavy metal removal from water.


Ten-year biochemical disease control for patients with prostate cancer treated with cryosurgery as primary therapy.
Prostate cryosurgery has been increasingly used for the management of localized prostate cancer since its introduction in a minimally invasive form in the early 1990s. We performed a retrospective study of the largest and most mature patient group treated with cryosurgery reported thus far. We retrospectively analyzed the data from 370 patients treated consecutively from 1991 to 1996 with a focus on the determination of biochemical disease-free survival for a group of patients with T1 to T3 prostate cancer who had undergone prostate cryosurgery as primary monotherapy. Only patients with no previous radiotherapy, hormonal therapy, or surgery were included. The median follow-up was 12.55 years. Using a nadir plus 2 ng/dL definition, Kaplan-Meier analysis demonstrated a biochemical disease-free survival rate at 10 years of 80.56%, 74.16%, and 45.54% for low, moderate, and high-risk groups, respectively. The 10-year negative biopsy rate was 76.96%. The results for this pilot group of patients who underwent percutaneous prostate cryosurgery monotherapy demonstrated biochemical disease-free survival rates that overlap with those of similar groups of patients treated under similar circumstances using other types of nonextirpative monotherapy.


Error augmentation feedback for lateral weight shifting.
This study examines the effect of error augmentation of center of pressure (CoP) visual feedback on the performance of a lateral weight shifting task. Error augmentation emphasizes deviations from a standard CoP trajectory generated from existing data of over 2000 weight shifts collected with young, healthy subjects. Thirty-six subjects completed nine lateral weight shifting sessions, of which four were training sessions between each of the five testing sessions. Half of the subjects received error augmentation feedback during the training sessions, while the other half received the unaltered, control feedback. The change in visual feedback did not affect the final steady state weight shifting performance. Instead, error augmentation feedback was found to drive subjects to their steady-state performance sooner than unaltered visual feedback. The emphasis on deviations from the standard trajectory with error augmentation appears to lead to reduced variation in shifting. This finding may be useful in generating novel therapies that improve the efficiency of balance rehabilitation.


On the prediction of cytotoxicity of diverse chemicals for topminnow (Poeciliopsis lucida) hepatoma cell line, PLHC-1$.
Two data sets on the cytotoxicity of diverse chemicals to topminnow (Poeciliopsis lucida) hepatoma cell line (PLHC-1) were modelled with quantitative structure-toxicity relationship (QSTR). The data sets are based on 3-amino-7-dimethylamino-2-methylphenazine hydrochloride (NR) and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assays representing lysosomal damage and metabolic impairment, respectively. The descriptors were calculated with DRAGON 6 and SPARTAN 10 software packages. Descriptor selection was made by 'all subset' and genetic algorithm-based features implemented in QSARINS software. The proposed QSTR models were validated both internally and externally. For both endpoints, statistically satisfactory QSTR models were generated with nTr = 39; r2Tr = 0.782; RMSETr = 0.466; nTest = 18; r2Test = 0.799; RMSETest = 0.360 for NR-based model and nTr = 32; r2Tr = 0.775; RMSETr = 0.460; nTest = 10; r2Test = 0.864; RMSETest = 0.290 for MTT-based model. Additionally, the QSTR models generated for NR and MTT endpoints were used to predict the cytotoxicity of an external set of 657 and 652 diverse chemicals with structural coverage of 98.6% and 98.3%, respectively. A moderate correlation was observed between the experimental in vivo and predicted in vitro values for external set chemicals. The QSTR models may provide an initial, rapid screening and prioritization of these diverse chemicals for the acute fish toxicity assessment and reduce the need for extensive in vivo toxicity testing.


Antiviral role of grouper STING against iridovirus infection.
Stimulator of interferon genes (STING, also known as MITA, ERIS, MPYS or TMEM173) has been identified as a central component in the innate immune response to cytosolic DNA and RNA derived from different pathogens. However, the detailed role of STING during fish iridovirus infection still remained largely unknown. Here, the STING homolog from grouper Epinephelus coioides (EcSTING) was cloned and its effects on IFN response and antiviral activity were investigated. The full-length EcSTING cDNA was composed of 1590 bp and encoded a polypeptide of 409 amino acids with 80% identity to STING homolog from large yellow croaker. Amino acid alignment analysis indicated that EcSTING contained 4 predicated transmembrane motifs (TMs) in the N terminal, and a C-terminal domain (CTD) which consisted of a dimerization domain (DD), c-di-GMP-binding domain (CBD) and a C-terminal tail (CTT). Expression profile analysis revealed that EcSTING was abundant in gill, spleen, brain, skin, and liver. Upon different stimuli in vivo, the EcSTING transcript was dramatically up-regulated after challenging with Singapore grouper iridovirus (SGIV), lipopolysaccharide (LPS) and polyinosin-polycytidylic acid (poly I:C). Reporter gene assay showed that EcSTING activated ISRE, zebrafish type I IFN and type III IFN promoter in vitro. Mutant analysis showed that IFN promoter activity was mostly mediated by the phosphorylation sites at serine residue S379 and S387. Moreover, EcSTING induced type I and III IFN promoter activity could be impaired by overexpression of EcIRF3-DN or EcIRF7-DN, suggesting that EcSTING mediated IFN response in IRF3/IRF7 dependent manner. In addition, the cytopathic effect (CPE) progression of SGIV infection and viral protein synthesis was significantly inhibited by overexpression of EcSTING, and the inhibitory effect was abolished in serine residue S379 and S387 mutant transfected cells. Together, our results demonstrated that EcSTING might be an important regulator of grouper innate immune response against iridovirus infection.


Occurrence and distribution of hexachlorocyclohexane isomers in vegetation samples from a contaminated area.
The occurrence and distribution of four major hexachlorocyclohexane (HCH) isomers (alpha-, beta-, gamma- and delta-) were studied in vegetation samples of a highly contaminated area close to a small-scale industrial belt in Lucknow (North India). Eight species of plants were collected at different points of the contaminated area and different parts of the plants were separated in order to study the difference in uptake and accumulation. The samples were extracted by matrix solid-phase dispersion (MSPD) extraction and finally determined by a gas-chromatograph equipped with (63)Ni electron capture detector (ECD). HCH isomers were present in almost all samples and the concentration of total HCH in the plant sample analyzed varied between 13 and 44 mg kg(-1), being the main isomer of beta-HCH (8-22 mg kg(-1)). Lindane (gamma-HCH) was present in all samples (1-9 mg kg(-1)). Solanum torvum Sw., and Erianthus munja shows the highest and lowest capacity for accumulation of HCH, respectively with a significant difference at p<0.01 level. The highest concentration of HCH residue in root samples indicates the most likely mechanism of HCH accumulation in these plants was sorption of soil HCH on roots. Solanum torvum Sw., and Withania somnifera (L.) Dunal could accumulate considerable levels of HCH isomers (44 and 34 mg kg(-1), respectively). The results reflect the importance of plants in monitoring purposes and their potential for phytoremediation of HCH contaminated soils.


High frequency residues: A new set of signals for detectability studies of an X-ray imaging system.
A new set of signals for studying detectability of an X-ray imaging system is presented. The results obtained with these signals are intended to complement the NEQ results. The signals are generated from line spread profiles by progressively removing their lower frequency components and the resulting high frequency residues (HFRs) form the set of signals to be used in detectability studies. Detectability indexes for these HFRs are obtained using a non-prewhitening (NPW) observer and a series of edge images are used to obtain the HFRs, the covariance matrices required by the NPW model and the MTF and NPS used in NEQ calculations. The template used in the model is obtained by simulating the processes of blurring and sampling of the edge images. Comparison between detectability indexes for the HFRs and NEQ are carried out for different acquisition techniques using different beam qualities and doses. The relative sensitivity shown by detectability indexes using HFRs is higher than that of NEQ, especially at lower doses. Also, the different observers produce different results at high doses: while the ideal Bayesian observer used by NEQ distinguishes between beam qualities, the NPW used with the HFRs produces no differences between them. Delta functions used in HFR are the opposite of complex exponential functions in terms of their support in the spatial and frequency domains. Since NEQ can be interpreted as detectability of these complex exponential functions, detectability of HFRs is presented as a natural complement to NEQ in the performance assessment of an imaging system.


Do multiple oestrogen receptor assays give significant additional information for the management of breast cancer?
In 101 breast cancer patients, measurement of oestrogen receptor status in multiple biopsies across a tumour reveals a highly significant difference in the proportion of patients remaining either disease-free (P less than 0.04) or alive (P less than 0.005), when those with uniformly receptor positive (++) primary tumours are matched with clinically comparable patients whose tumours were homogeneously receptor negative (--). Mean follow-up time was 85 months. The prognostic value of this discriminant is particularly striking in the 53 patients with involved nodes at presentation. Of these, 13 were (++) and seven remain alive of whom six are disease-free, whereas 24 of the 29 (--) patients are dead. These results further suggest that receptor assay on a single homogenate gives less clinical information than do assays on multiple biopsies across the tumour. For patients with involved nodes, clinical management may best be decided after determination of 'macroheterogeneity'.


Immunohistochemical investigation of mid-dermal elastolysis.
We report a 31-year-old Caucasian woman presenting with remarkable wrinkling on her trunk and proximal extremities. Diagnosis of mid-dermal elastolysis (MDE) was confirmed by Van Gieson's staining. Immunohistochemical investigations revealed enhanced expression of CD34+ and CD68+ cells accompanied by slightly increased expression of CD3+ and CD4+ lymphocytes in lesional skin. Furthermore an elevated cellular expression of matrix metalloproteinase (MMP)-1 and slightly increased presence of MMP-12 positive cells combined with a decrease of tissue inhibitor of metalloproteinases 1 (TIMP-1) positive cells was observed in lesional skin as compared with a control specimen obtained from nonlesional skin. Our data may indicate inflammatory processes and an altered balance between MMPs and TIMPs in MDE. Furthermore CD34+ dendritic fibroblasts and/or histiocytes are possibly involved in the pathogenesis of MDE.


Results of operative therapy in the permanent form of junctional reciprocating tachycardia.
To assess the results of operative therapy for permanent junctional reciprocating tachycardia, a type of incessant tachycardia, the clinical and electrophysiologic data of 8 such patients referred for management of tachycardia were reviewed. The duration of incessant tachycardia was 14 +/- 10 years (range 2 to 30). The heart rate at rest during tachycardia ranged from 120 to 150 beats/min. Four of 8 patients had cardiomegaly or depressed ejection fraction (16 +/- 10%, range 5 to 27) at presentation and, of these, 2 had symptoms of congestive heart failure. Exertional dyspnea despite normal left ventricular function was noted in 1 patient, 2 had chronic palpitations and 3 were asymptomatic. Electrophysiologic data confirmed the presence of a posteroseptal pathway with atrioventricular node-like properties conducting slowly in the retrograde direction only. Seven patients underwent successful surgical ablation of the accessory pathway. Hypothermic cardiopulmonary bypass was used in 2 and a closed heart technique without cardiopulmonary bypass in the other 5. Three of 4 patients with reduced left ventricular function showed an improvement in ejection fraction to 34 +/- 20% (range 16 to 63) after control of dysrhythmia. Three patients had no evidence of cardiomegaly despite equivalent periods of incessant tachycardia. Another patient with normal left ventricular function despite incessant tachycardia for over 30 years underwent spontaneous remission to sinus rhythm and did not undergo surgery. These data suggest that permanent junctional reciprocating tachycardia has a variable presentation and that congestive heart failure is not an infrequent presenting symptom. The substrate is invariably an accessory atrioventricular pathway with a long conduction time and decremental properties conducting only in the retrograde direction.(ABSTRACT TRUNCATED AT 250 WORDS)


Laying the foundation: teaching policy and advocacy to medical trainees.
A novel and comprehensive two-year health policy curriculum was developed and implemented for family medicine residents at two University of Toronto-affiliated teaching sites. To evaluate the impact of the curriculum on residents' knowledge of health policy issues, and its usefulness to their learning. The evaluation included a pre-post delivery assessment of residents' content-based knowledge of issues in the Canadian healthcare system. Residents were also asked to evaluate the content, process and usefulness of the health policy curriculum. At the end, more than two-thirds of residents had a better understanding of the Canadian healthcare system. The overall pre-post scores showed that residents retained content-based facts in some detail. However, more importantly, residents' positive evaluations of the curriculum indicated they were engaged, enthusiastic and recognized its importance for their learning. Despite residents' positive evaluations, questions remain as to how best to assess the success of health policy curricula. Moving beyond the popular pre-post test, less traditional approaches might complement standard program evaluation methods in future. As educators increasingly develop curricula aimed at non-biomedical expertise, we must consider how we can most meaningfully evaluate long-term impact on graduates' approach to clinical practice and their engagement in health system advocacy.


Prognostic implications of downstaging following preoperative radiation therapy for operable T3-T4 rectal cancer.
To evaluate the prognostic value of tumor downstaging after preoperative radiation for resectable rectal cancer. Eighty-eight patients with non-metastatic resectable rectal cancers (76 T3 and 12 T4) were treated with preoperative irradiation. Median dose was 40 Gy (30-46 Gy) delivered over 32 days (range 11-40). Seventeen patients received preoperative chemotherapy, two courses of 5-fluorouracil (5FU) 350 mg/m2/day and folinic acid 20 mg/m2/day; 5 days per week during the first and fifth weeks of radiotherapy. Surgery was performed with a mean delay of 46 days after completion of irradiation and included 66 abdominoperineal resections and 22 anal sphincter-preserving procedures. Postoperative chemotherapy was administered in 44 patients. Histological tumor stages were: complete histological response in 7%, pT2N0 in 19%, pT3N0 in 46%, and pT2-3N1 in 28%. Tumor downstaging occurred in 26%. No predictive factor of downstaging was statistically significant. The median follow-up was 33 months. The 3- and 5-year cancer-specific survival rates were 100% for the pT0N0 and pT2N0, respectively, 89% and 68% for pT3N0, and 64% and 0% for pT2T3N1. After preoperative irradiation, the pathological tumor stages remained a prognostic factor. Patients with downstaging (pT0T2N0) had significantly higher cancer-specific survival rates than the group without downstaging: 100% and 80% at 3 years, and 100% and 45% at 5 years; respectively (p = 0.011). The 3- and 5-year recurrence free-survival rates were 94% for the group with downstaging and 56% and 50%, respectively, for the group without downstaging (p = 0.002). Downstaging after preoperative irradiation in this retrospective study results in an improvement in local control and survival.


5-(Chloromethyl)furfural is the New HMF: Functionally Equivalent But More Practical in Terms of its Production From Biomass.
5-(Chloromethyl)furfural (CMF) is a disruptive innovation in the biorefinery. Chemically, it is at least as versatile as the well-known HMF but, unlike HMF, it is accessible in high yield directly from cellulosic biomass due to its lipophilicity and stability under acidic conditions, which facilitate isolation. It has a rich derivative chemistry that includes biofuels, renewable polymers, specialty chemicals, and value-added agrochemical and pharmaceutical products.


FBXL10 promotes EMT and metastasis of breast cancer cells via regulating the acetylation and transcriptional activity of SNAI1.
F-box and leucine-rich repeat protein 10 (FBXL10) has been reported to play a regulatory role in the initiation and development of breast cancer. Bioinformatics analyses revealed that FBXL10 may involve in the process of cytoskeleton organization. This research aimed to investigate the function of FBXL10 in epithelial-mesenchymal transition (EMT) and metastasis of breast cancer, and tried to reveal the molecular mechanism involved in this issue. Functional experiments in vitro revealed that FBXL10 promoted the migration and invasion of breast cancer cells through inhibiting E-cadherin expression and inducing EMT. Mechanical studies revealed that FBXL10 could specifically interact with SNAI1, but not Slug or ZEB1. And it promoted the transcriptional repression activity of SNAI1 on CDH1 in breast cancer cells. Furthermore, FBXL10 had a positive role for the deacetylation of SNAI1 by facilitating the interaction between SNAI1 and HDAC1, a dominating deacetylase of SNAI1. And the deacetylated SNAI1 showed a more suppressive ability to inhibit the transcription of E-cadherin. Moreover, mouse models were also conducted to confirm the effect of FBXL10 on the lung metastasis of breast cancer in vivo. Totally, our data revealed that FBXL10 served as a pro-metastatic factor in breast cancer via repressing the expression of E-cadherin and inducing EMT. It may provide a novel regulatory axis in the EMT of breast cancer.


Efficacy of an anterior as compared with a posterior laparoscopic partial fundoplication: results of a randomized, controlled clinical trial.
The aim of the study was to compare the efficacy and mechanical consequences of 2 partial fundoplications performed laparoscopically under the framework of a randomized, controlled clinical trial. Although laparoscopic total fundoplication procedures have proven their effectiveness in the control of gastroesophageal reflux, problems remain with the functional consequences after a supra-competent gastric cardia high-pressure zone. Partial fundoplications have been found to be associated with fewer mechanical side effects. During a 2-year period, 95 patients with gastroesophageal reflux disease were enrolled into a randomized, controlled single-institution clinical trial comparing a partial posterior (Toupét, n = 48) fundoplication and an anterior partial wrap (Watson, n = 47). All patients were assessed postoperatively at predefined time points, and the 12-month follow-up data are presented in terms of clinical results and 24-hour pH monitoring variables. Both patient groups were strictly comparable at the time of randomization. All operations were completed laparoscopically, and no serious complications were encountered. During the first postoperative year, a difference regarding the control of reflux symptoms was observed in favor of the posterior fundoplication. Esophageal acid exposure (% time pH <4) was substantially reduced by both operations but to a significantly lower level after a Toupét compared with the Watson partial fundoplication (1.0 +/- 0.3 vs. 5.6 +/- 1.1 mean +/- SEM; p < 0.001). Postfundoplication symptoms were infrequently recorded with no difference between the groups. When performing a laparoscopic partial fundoplication, the posterior modification (Toupét) offers advantages in terms of better reflux control compared with an anterior type (Watson).


Influence of different types of commercially available microcrystalline cellulose on degradation of perindopril erbumine and enalapril maleate in binary mixtures.
Influence of some commercially available types of microcrystalline cellulose (MCC) on the stability of certain active pharmaceutical ingredients (APIs), when in contact, has been investigated. Two structurally similar APIs, perindopril erbumine (PER) and enalapril maleate (EM), both well-known angiotensin-converting enzyme inhibitors were used. The main properties of an MCC that could determine the stability for each API were measured and correlated to the stability of these two APIs in binary mixtures. The stability of these APIs differed when in contact with different types of MCC. The dominant properties of MCC from one manufacturer were surface features that influenced the stability of PER and acidity that influenced the stability of EM. In the case of MCC from other manufacturers, unbound water was stability determining for both substances.


Enzymatic activity of adenylate cyclase toxin from Bordetella pertussis is not required for hemolysis.
Adenylate cyclase (AC) toxin from Bordetella pertussis enters cells to cause supraphysiologic increases in cAMP. AC toxin is also hemolytic. Substitution of Lys-58 with a methionine residue by site-directed mutagenesis of the structural gene for AC toxin, cyaA, and introduction of this mutation onto the B. pertussis chromosome results in an organism that synthesizes an enzyme-deficient AC toxin molecule. This mutant toxin molecule exhibits 1000-fold reduction in enzymatic activity relative to wild-type and has no toxin activity in J774 cells. The enzyme-deficient toxin molecule is not, however, impaired in its ability to lyse sheep red blood cells. In order to ascertain the importance of these two separate activities of AC toxin in vivo the enzyme-deficient organisms were used to infect infant mice. The hemolytic, enzyme-deficient mutant organisms are reduced in virulence relative to wild-type organisms after intranasal challenge indicating that, although the enzymatic activity of AC toxin does not contribute to hemolysis, it is this property of the toxin which is important for virulence of B. pertussis.


Improving pulse oximetry accuracy in dark-skinned patients: technical aspects and current regulations.
Recent concerns regarding the clinical accuracy of pulse oximetry in dark-skinned patients, specifically in detecting occult hypoxaemia, have motivated research on this topic and recently reported in this journal. We provide an overview of the technical aspects of the issue, the sources of inaccuracy, and the current regulations and limitations. These insights offer perspectives on how pulse oximetry can be improved to address these potential limitations.


Role of the ubiquitin-selective CDC48(UFD1/NPL4 )chaperone (segregase) in ERAD of OLE1 and other substrates.
The OLE pathway of yeast regulates the abundance of the ER-bound enzyme Delta-9 fatty acid desaturase OLE1, thereby controlling unsaturated fatty acid pools and membrane fluidity. Previously, we showed that this pathway is exquisitely regulated by the ubiquitin/proteasome system. Activation of the pathway involves proteasomal processing of a membrane-bound transcription factor and the subsequent mobilization of the cleaved, ubiquitylated transcription factor from its partner molecule by CDC48(UFD1/NPL4), a ubiquitin-selective chaperone-like enzyme. Here we report that the OLE1 protein itself is naturally short-lived and is degraded by ubiquitin/proteasome-dependent ER-associated degradation (ERAD). We found that CDC48(UFD1/NPL4) plays a second role in the OLE pathway by mediating ERAD of OLE1. Intriguingly, other ERAD substrates also require CDC48(UFD1/NPL4) for degradation, indicating that this enzyme is a novel, constitutive component of the ERAD machinery. We propose that CDC48(UFD1/NPL4) functions as a segregase that liberates ubiquitylated proteins from non-modified partners.


Management of prostate cancer after holmium laser enucleation of the prostate.
Holmium laser enucleation of the prostate (HoLEP) is effective in treating lower urinary tract symptoms from prostatic disease. We investigate the role of HoLEP in the management of patients with benign prostatic hypertrophy (BPH) and prostate cancer (CaP). Retrospective review of data regarding all patients undergoing HoLEP at a single institution was performed. Pre- and postoperative PSA, multiparametric MRI, and pathology results were analyzed for those with CaP identified prior to or incidentally at HoLEP. From February 2016 to February 2020, 201 patients underwent HoLEP. Twelve patients had CaP diagnosed before HoLEP: 6 patients with GG1 are on active surveillance (AS), 3 of 4 intermediate-risk patients are on AS and 1 received treatment for disease progression, and both high-risk CaP patients achieved symptomatic benefit from HoLEP and are receiving systemic therapy for CaP. Twenty-one patients (11.1%) with incidentally detected CaP at HoLEP remain on AS or watchful waiting based on clinical scenario. Screening for CaP in HoLEP candidates with PSA and MRI is recommended given that >10% will have incidental CaP. After HoLEP for BPH/LUTS, patients with CaP can be surveilled with PSA and/or MRI. Further investigation is warranted to determine the durability of success of these approaches.


Prevalence and risk factors for overweight and obesity in children from Seychelles, a country in rapid transition: the importance of early growth.
To establish the prevalence of overweight and obesity and related risk factors in children from Seychelles (Indian Ocean), a country in rapid economic and epidemiological transition. Cross-sectional study with retrospective access to early life data. All children from all schools of Seychelles, in four selected school grades (kindergarten, fourth, seventh and tenth year of obligatory school) in 1999. A total of 5514 children aged 4.5-17.4 y were measured, corresponding to 83.5% of the eligible population. Overweight and obesity, using age- and sex-specific body mass index (BMI) cut-off points as defined by the International Obesity Task Force. Some 12.6% (95% confidence interval: 11.8-13.5%) of the children were overweight and 3.8% (3.3-4.4%) were obese. Weight gain (kg) during the first year of life was strongly associated with subsequent overweight (odds ratio 1.46, 95% confidence interval 1.27-1.67) and obesity (1.59, 1.29-1.97) in childhood, independently of birth weight. Increased maternal BMI (kg/m(2)) was also associated with overweight (1.07, 1.03-1.10) and obesity (1.09, 1.04-1.14) in the offspring. Prevalence of overweight and obesity among school children in Seychelles was as high as or higher than in some industrialized countries. If confirmed in other environments, the strong association between weight gain during the first year of life and subsequent obesity in childhood could affect the way optimal infant weight gain is defined in countries where public health priorities are changing.


Search for bacteriophages spontaneously occurring in cultures of haemolytic intestinal spirochaetes of human and animal origin.
An electron microscopic survey of the occurrence of bacteriophages which appear spontaneously in cultures of haemolytic intestinal spirochaetes of human and animal origin was made. Excluding one isometric tailed phage particle which was observed in the form of free particle in proximity to a spirochaete of the w beta HIS strain HRM18, bacteriophages were never observed while examining cells of 21 weakly beta-haemolytic human intestinal spirochaetes (w beta HIS), swine Serpulina pilosicoli strain P43/6/78, and the avian strain 1380, although 50-100 cells of each spirochaetal strain were analysed. Isometric tailed bacteriophages were found associated with only three out of the 100 cells of strongly beta-haemolytic swine Serpulina hyodysenteriae strain P18A comparatively analysed. According to our results and previous published reports, the occurrence of bacteriophages which appear spontaneously in cultures of intestinal spirochaetes is a rare event.


Prospects and limitations of e-learning application in private tertiary institutions amidst COVID-19 lockdown in Nigeria.
E-learning has numerous potentials to spur education development in tertiary institutions in Nigeria. It impacts positively on the educational process, unlike the physical chalkboard in the classrooms. The outbreak and fast spread of the COVID-19 led to the closed down of schools. Efforts to revamp education due to prolong lockdown made the government enforce e-learning in tertiary institutions across the country. It is however worthy to know that these directives did not make much change as a result of poor infrastructure and networking. Hence, this study investigated compliance with e-learning during COVID-19 pandemic lockdown by the instructors in the private tertiary institutions in Nigeria vis-à-vis their socio-economic factors and limitations encountered. A systematic sampling technique was adopted to select 180 respondents from the staff list. A validated questionnaire was used to collect data on socio-economic variables (SEV), compliance (ϒ) to e-learning, and limitations (Ls) while multiple linear regression model (R) was used to test the interaction between the compliance and limitations. Results show that age (β = 0.351), educational attainment (β = 0.843) and teaching experience (β = 0.169) influence e-learning compliance at p < 0.05. It was also found that 67.3% compliance with e-learning took place in the Universities compared to 59.1% in the Polytechnics and 52.8% in the Colleges of Education. Regression shows that constraints affected the level of compliance (R2 = 0.73). The study concludes that constraints are major obstacles to the compliance and prospects of e-learning in the Private Tertiary Institutions in Nigeria.


Pharmacokinetic Analysis of [18F]FAZA Dynamic PET Imaging Acquisitions for Highlighting Sacrum Tumor Profiles.
A patient enrolled in a clinical trial (NCT02802969) with suspicion of chordoma underwent an [F]FAZA PET/CT, a radiolabeled nitroimidazole analog of hypoxia PET imaging. The patient's images showed a different tumor profile compared to those observed in other hypoxic or nonhypoxic chordoma patients. The motivation for using [F]FAZA pharmacokinetic imaging was to compare this profile with histologically confirmed cases of chordoma. Through visual imaging and quantification of blood and tumor time-activity curves, we excluded the hypothesis that it was a chordoma, diagnosing a paraganglioma.


Interdisciplinary management of a patient with a bilateral cleft lip and palate and 12 congenitally missing teeth.
This article reports the interdisciplinary treatment of a girl born with a complete bilateral cleft lip and palate. She had congenitally missing maxillary lateral incisors and canines and mandibular incisors, canines, and second premolars in addition to third molars. At age 11 years 2 months, she was treated with rapid maxillary expansion followed by bonding of the maxillary arch. Cranial harvested alveolar bone graft surgery was done at age 17 years 2 months. Mandibular arch treatment was started at age 19 years using single tooth implants initially as orthodontic anchorage devices and secondarily as prosthetic abutments. Teeth were placed in strategic positions for a 4 incisor fixed partial denture cemented on the 2 lateral incisor implants and screw-retained crowns on premolar implants. The maxillary arch was restored with screw-retained crowns on canine implants with lateral incisors in cantilever and pink ceramic. Two years posttreatment records at age 22 years 6 months showed long-term stability with good occlusion, facial balance, and smile esthetics.


Fructose impairs fat oxidation: Implications for the mechanism of western diet-induced NAFLD.
Increased fructose intake from sugar-sweetened beverages and highly processed sweets is a well-recognized risk factor for the development of obesity and its complications. Fructose strongly supports lipogenesis on a normal chow diet by providing both, a substrate for lipid synthesis and activation of lipogenic transcription factors. However, the negative health consequences of dietary sugar are best observed with the concomitant intake of a HFD. Indeed, the most commonly used obesogenic research diets, such as "Western diet", contain both fructose and a high amount of fat. In spite of its common use, how the combined intake of fructose and fat synergistically supports development of metabolic complications is not fully elucidated. Here we present the preponderance of evidence that fructose consumption decreases oxidation of dietary fat in human and animal studies. We provide a detailed review of the mitochondrial β-oxidation pathway. Fructose affects hepatic activation of fatty acyl-CoAs, decreases acylcarnitine production and impairs the carnitine shuttle. Mechanistically, fructose suppresses transcriptional activity of PPARα and its target CPT1α, the rate limiting enzyme of acylcarnitine production. These effects of fructose may be, in part, mediated by protein acetylation. Acetylation of PGC1α, a co-activator of PPARα and acetylation of CPT1α, in part, account for fructose-impaired acylcarnitine production. Interestingly, metabolic effects of fructose in the liver can be largely overcome by carnitine supplementation. In summary, fructose decreases oxidation of dietary fat in the liver, in part, by impairing acylcarnitine production, offering one explanation for the synergistic effects of these nutrients on the development of metabolic complications, such as NAFLD.


Roles of neuropeptide Y and noradrenaline in sympathetic neurotransmission to the thoracic vena cava and aorta of guinea-pigs.
The roles of neuropeptide Y (NPY) and noradrenaline (NA) in sympathetic neurotransmission to large arteries and veins were studied in vitro using the thoracic portions of the aorta and inferior vena cava from guinea-pigs. Both vessels are densely innervated by axons containing NA and NPY. Repetitive transmural stimulation at 2-30 Hz produced contractions of the aorta, which were abolished by prazosin. NPY did not have significant postsynaptic or presynaptic effects on vascular tone of the aorta. Transmural stimulation of the vena cava produced long-lasting contractions which were enhanced by alpha- and beta-adrenoceptor antagonists, and were blocked by guanethidine. Precontracted venae cavae responded to sympathetic stimulation with beta-adrenoceptor-mediated relaxation, followed by contraction. alpha-Adrenoceptor blockade delayed the onset of neurogenic contractions. NPY was a potent contractile agent of the vena cava (EC50 approximately 1.5 x 10(-8) M). A high concentration (3 x 10(-6) M) of NPY, or the specific NPY Y1 receptor agonist, [Leu31, Pro34]NPY, caused parallel, and reversible, desensitization of contractions produced by sympathetic nerve stimulation, and by low concentrations of exogenous NPY. This provides good evidence that NPY is the mediator of the non-adrenergic sympathetic contractions of the vena cava. Furthermore, these results demonstrate that differential location or coupling of postsynaptic receptors for NA and NPY in the aorta and vena cava, leads to differential participation by these substances in sympathetic vasomotor responses. This is likely to be related to the different functions of these two parts of the systemic circulation.


Imaging assessment of groin pain.
Groin pain is a common condition in athletes, especially those who play certain sports, for instance soccer, ice hockey, fencing which request rapid acceleration and frequent changes of movement. This condition represents a diagnostic difficulty for the radiologist due to either the anatomical pubic region complexity than the many causes that can be a source of pain, because the groin pain can be determined by conditions affecting the bony structures, cartilage and muscle tendons that are part of the proper pubis but also from those involving the hip. The approach to the groin through diagnostic imaging is multidisciplinary: The study of the patient is performed by traditional radiographs, ultrasound examination, magnetic resonance imaging or computed tomography, based on clinical suspicion, and each of these methods provides different results depending on the disease in question. The purpose of this article is to examine what are the optimal imaging techniques to investigate the various diseases affecting the patient with groin pain.


Platelet-derived growth factor is a chemoattractant for vascular smooth muscle cells.
In previous experiments (Grotendorst et al, 1981), we showed that platelet-derived growth factor promotes the migration of smooth muscle cells in vitro. Using a "checkerboard" analysis, we now establish that platelet-derived growth factor (PDGF) acts as a true chemoattractant for cultured aortic smooth muscle cells. Other growth factors such as epidermal growth factor, fibroblast growth factor, and insulin are not chemoattractants. The chemotactic response occurs before the initiation of DNA synthesis and is not affected by inhibition of DNA synthesis. Chemotaxis occurs at levels of PDGF lower than required for mitogenesis. RNA and protein synthesis are required for the chemotactic response. As found previously in bacteria and leucocytes, we find that methylation reactions are required for the chemotactic response. The possibility is discussed that PDGF acts in vivo at sites of vascular injury to attract smooth muscle cells from the medial layer to the luminal surface, and is involved in the early stages of the formation of atherosclerotic plaques.


Speciation analysis of inorganic arsenic in coal samples by microwave-assisted extraction and high performance liquid chromatography coupled to hydride generation atomic fluorescence spectrometry.
A new method was developed for the speciation analysis of inorganic arsenic in coal samples by high performance liquid chromatography coupled to hydride generation atomic fluorescence spectrometry after microwave-assisted extraction. Effective extract of As(III) and As(V) in coal sample was achieved by 1.0 mol L(-1)H₃PO₄ and 0.1 mol L(-1)ascorbic acid. Under the optimized conditions, the limits of detection (LOD) were 0.01 μg L(-1) and 0.02 μg L(-1), the relative standard deviations (RSD) were 2.4% and 3.3% (c=10.0 μg L(-1), n=7), recoveries were 102.5% and 96.5% for As(III) and As(V). The proposed method was successfully applied for the determination of speciation of inorganic arsenic in coal samples and GBW11117 coal standard reference material with complex matrix.


Post-traumatic left ventricular aneurysm with massive hemopericardium in a child presenting 3 years after a fall.
A 7-year-old boy developed a left ventricular aneurysm with massive hemopericardium 3 years ago due to a fall from a fourth-floor window. He had mild neurological sequelae including cranial nerve III palsy and abnormal electroencephalography findings at that time. He had no chest pain until recently when he presented with chest tightness and abdominal pain for 2 days prior to admission. Chest X-ray showed marked cardiomegaly. Echocardiography revealed massive pericardial effusion and a large left ventricular aneurysm. The massive hemopericardium was surgically drained, and the aneurysm was resected under cardiopulmonary bypass. He was discharged uneventfully 1 week after operation. Because symptoms and signs can vary in patients with ventricular aneurysm, we strongly suggest a close clinical follow-up, preferably with chest X-ray or echocardiography, for patients experiencing a blunt chest trauma.


An example of designed multiple ligands spanning protein classes: dual MCH-1R antagonists/DPPIV inhibitors.
A ligand-based approach to identify potential starting points for a dual MCH-1R antagonist/DPPIV inhibitor medicinal chemistry program was undertaken. Potential ligand pairs were identified by analysis of MCH-1R and DPPIV in vitro data. A highly targeted synthetic effort lead to the discovery of pyridone 11, a dual MCH-1R antagonist/DPPIV inhibitor with selectivity over DPP8 and DPP9.


Tuneable endogenous mammalian target complementation via multiplexed plasmid-based recombineering.
Understanding the quantitative functional consequences of human disease mutations requires silencing of endogenous genes and expression of mutants at close to physiological levels. Changing protein levels above or below these levels is also important for system perturbation and modelling. Fast design optimization demands flexible interchangeable cassettes for endogenous gene silencing and tuneable expression. Here, we introduce 'TEMTAC', a multigene recombineering and delivery system for simultaneous siRNA-based knockdown and regulated mutant (or other variant) expression with different dynamic ranges. We show its applicability by confirming known phenotypic effects for selected mutations for BRAF, HRAS, and SHP2.