Evolution of Zinc Oxide Nanostructures Grown on Graphene by Ultrasonic Spray Pyrolysis and Its Statistical Growth Modelling.
The evolution of zinc oxide nanostructures grown on graphene by alcohol-assisted ultrasonic spray pyrolysis was investigated. The evolution of structures is strongly depended on pyrolysis parameters, i.e., precursor molarity, precursor flow rate, precursor injection/deposition time, and substrate temperature. Field-effect scanning electron microscope analysis, energy dispersive X-ray spectroscopy, X-ray diffraction, and transmission electron microscopy were used to investigate the properties of the synthesized nanostructures and to provide evidence for the structural changes according to the changes in the pyrolysis parameters. The optimum parameters to achieve maximum density and well-defined hexagonally shaped nanorods were a precursor molarity of 0.2 M, an injection flow rate of 6 ml/min, an injection time of 10 min, and a substrate temperature of 250-355 °C. Based on the experimental results, the response surface methodology (RSM) was used to model and optimize the independent pyrolysis parameters using the Box-Behnken design. Here, the responses, i.e., the nanostructure density, size, and shape factor, are evaluated. All of the computations were performed using the Design-Expert software package. Analysis of variance (ANOVA) was used to evaluate the results of the model and to determine the significant values for the independent pyrolysis parameters. The evolution of zinc oxide (ZnO) structures are well explained by the developed modelling which confirms that RSM is a reliable tool for the modelling and optimization of the pyrolysis parameters and prediction of nanostructure sizes and shapes.


Role of phosphatidylinositol 3-kinase activation in the hypertrophic growth of adult ventricular cardiomyocytes.
The present study investigated whether activation of phosphatidylinositol 3-kinase (PI3-kinase) is involved in the stimulation of hypertrophic growth of adult ventricular cardiomyocytes under alpha- or beta-adrenoceptor stimulation. Adult ventricular rat cardiomyocytes were used either directly after isolation (day 1 culture) or after cultivation for 6 days in presence of 20% fetal calf serum (day 7 culture). PI3-kinase activity was determined in extracts of cardiomyocytes after immunoprecipitation with an antibody against the p85 subunit of PI3-kinase. The influence of PI3-kinase inhibition on myocardial growth was determined using the specific PI3-kinase inhibitors wortmannin and LY294002. In day 1 cultures alpha-adrenoceptor stimulation, but not beta-adrenoceptor stimulation caused activation of PI3-kinase. In response to alpha-adrenoceptor stimulation but not beta-adrenoceptor stimulation an acceleration of protein synthesis (incorporation of 14C-phenylalanine) and an increase in the total masses of cellular protein and RNA was observed. In these cultures inhibition of PI3-kinase attenuated the acceleration of protein synthesis and the increase in cellular masses of protein or RNA in response to alpha-adrenoceptor stimulation. In day 7 cultures alpha- and beta-adrenoceptor stimulation caused activation of PI3-kinase and increased protein synthesis. In these cultures inhibition of PI3-kinase attenuated the growth response to alpha- and beta-adrenoceptor stimulation. PI3-kinase activation via protein kinase C-dependent or cAMP-dependent pathways is required for hypertrophic growth of adult cardiomyocytes.


Influence of food intake on the enantiomeric composition of urinary salsolinol in man.
Salsolinol is present in human fluids and tissues as well as in foods and beverages. It was shown previously that the R enantiomer of salsolinol predominates in human urine, whereas the S enantiomer predominates in Port wine. An R/S ratio very near to 1 was found in dried banana, a food particularly rich in salsolinol. In this study 100 g of dried banana were administered to 6 healthy subjects. The urinary excretion of the R and S enantiomers of salsolinol was measured 24h before and 24h after banana intake, each time in two fractions. Whereas the S enantiomer was present only in the fraction 5 p.m.-9 a.m. and only in 3 out of the 6 subjects before banana intake, this enantiomer was found in the two intervals 9 a.m.-5 p.m. and 5 p.m.-9 a.m. in all the subjects after banana intake. The presence of the S enantiomer in urine in 3 subjects before dried banana might be related to alcohol intake. The amount of R + S salsolinol eliminated in the 24h urine was found to represent 0.75% of the total dose administered. In conclusion a normal diet should have a negligible influence on urinary salsolinol concentrations, with, perhaps, the exception of alcohol; interestingly the R enantiomer might represent endogenous salsolinol.


Application of LCA modelling in integrated waste management.
Life cycle assessment (LCA) has been used in waste management for the last two decades and hundreds of journal papers have been published. The use of LCA in waste management has provided a much-improved holistic view of waste management including waste flows and potential environmental impacts. Although much knowledge has been obtained from LCA studies, there is still a need to use LCA models in integrated waste management. This paper describes six areas where LCA is expected to play a role in waste management in the future: 1) understanding an existing waste management system; 2) improving existing waste management systems; 3) comparing alternative technologies/ technology performance; 4) technology development/prospective technologies; 5) policy development/strategic development; and 6) reporting. Illustrative examples are provided for each application area.


Carbon storage capacity of Castanopsis hystrix plantations at different stand-ages in South China.
The establishment of forest plantations is an excellent silvicultural alternative to improve atmospheric carbon (C) sequestration for climate change mitigation. In recent years, the importance of forest growth and C dynamics at different stand ages have drawn huge attention for investigation. To evaluate the impacts of different stand ages on the C storage capacity of Castanopsis hystrix plantations ecosystems, we measured biomass and C content in trees, understory, litter, and soil components from field measurements at different stand ages, i.e., 6-, 10-, 15-, 25-, and 34-year-old stands. Results showed that the C stocks in trees, understory vegetation, litter, soil and the whole ecosystem increased steadily with stand age. C. hystrix C storage capacity in the 6-, 10-, 15-, 25-, and 34-year-old stands were 29.17, 56.18, 85.60, 132.19 and 157.79 Mg ha-1, respectively, while the total ecosystem C storage capacity was 68.11, 106.11, 136.13, 187.34 and 226.14 Mg ha-1, respectively. Meanwhile, the C sequestration rate in the 6-10, 10-15, 15-25 and 25-35-year-old stands were 675.28, 588.35, 465.97 and 284.39 g m2 year-1, respectively. Similarly, total biomass of trees, understory, and litter increased with stand age. Our study indicated that C. hystrix plantations are still developing in the area, since live biomass and soil C continue to accumulate despite reduced C sequestration rates. The information provided here highlight the C stock and C sequestration rates of C. hystrix at different stand ages, providing baseline information on the C dynamics of young and older stand of C. hystrix in this region; Hence, such knowledge could be useful for designing more realistic policies to mitigate climate change, such as programs to maintain continuous forest growth.


Do patient characteristics affect the predictive validity of Functional Capacity Evaluations?
The aim of this study was to identify patient-related characteristics that affect the predictive validity of the FCE assessment ELA. A prospective multicenter study was conducted on 303 patients with musculoskeletal disorders (MSD) recruited from eleven rehabilitation centers. The ELA-based estimation of the participants' ability to cope with physical work demands was considered valid if RTW was paired with a positive ELA outcome (≥ moderate) as well as if non-RTW was accompanied by a negative ELA outcome (rather or very poor). In the remaining cases, the ELA result was judged as non-valid. To reduce the risk of false conclusions, the rating was performed inversely in participants that (1) reported severe limitations regarding their productivity at work, (2) attributed RTW to a change in job resp. a reduction of their physical work demands and in those that (3) attributed non-RTW to non-physical reintegration barriers only. Using questionnaires, 28 patient-related characteristics were collected. Logistic regression models were calculated to identify characteristics that affected the predictive validity of ELA. ELA was considered valid in 208 of 303 (69%) participants. A moderate and strong pain-related disability at work were associated with a 0.15-fold (95% confidence interval (95% CI) 0.05-0.46), respectively, 0.19-fold (95% CI 0.05-0.72) chance for a valid outcome. In addition, a negative influence was found in participants that reported psychosocial distress (odds ratio (OR) 0.35; 95% CI 0.15-0.82), a native language different from the national language (OR 0.16; 95% CI 0.05-0.56) as well as in those that expected to return to work, but not within one month (OR 0.17; 95% CI 0.06-0.46). Further variables-including age, employment status, fear-avoidance beliefs and the level of physical work demands-did not affect the predictive validity of ELA. The results suggest that the predictive validity of ELA is primarily limited by patients that report a moderate or strong pain-related disability at work, psychosocial distress as well as the expectation to return to work, but not within one month. Furthermore, a negative influence can be assumed for language barriers.


Reshaping the Tumor Immune Microenvironment Based on a Light-Activated Nanoplatform for Efficient Cancer Therapy.
The immunosuppressive tumor microenvironment (TME) always causes poor antitumor immune efficacy, prone to relapse and metastasis. Herein, novel poly(vinylpyrrolidone) (PVP) modified BiFeO3 /Bi2 WO6 (BFO/BWO) with a p-n type heterojunction is constructed for reshaping the immunosuppressive TME. Reactive oxygen species can be generated under light activation by the well-separated hole (h+ )-electron (e- ) pairs owing to the heterojunction in BFO/BWO-PVP NPs. Interestingly, h+ can trigger the decomposition of H2 O2 to generate O2 for alleviating tumor hypoxia, which not only sensitizes photodynamic therapy (PDT) and radiotherapy (RT), but also promotes tumor-associated macrophages (TAMs) polarization from M2 to M1 phenotype, which is beneficial to decrease the expression of HIF-1α. Importantly, such a light-activated nanoplatform, combining with RT can efficiently activate and recruit cytotoxic T lymphocytes to infiltrate in tumor tissues, as well as stimulate TAMs to M1 phenotype, dramatically reverse the immunosuppressive TME into an immunoactive one, and further boost immune memory responses. Moreover, BFO/BWO-PVP NPs also present high performance for computed tomography imaging contrast. Taken together, this work offers a novel paradigm for achieving O2 self-supply of inorganic nanoagents and reshaping of the tumor immune microenvironment for effective inhibition of cancer as well as metastasis and recurrence.


Supercritical emulsion extraction fabricated PLA/PLGA micro/nano carriers for growth factor delivery: Release profiles and cytotoxicity.
Controlled delivery of human growth factors is still a challenge in tissue engineering protocols, and poly-lactic acid and poly-lactic-co-glycolic acid carriers have been recently proposed for this purpose. Here, the microencapsulation of two human growth factors, namely Growth Differentiation Factor -5 (hGDF-5) and Transforming Growth Factor β1 (hTGF-β1) was tested, by processing different emulsions with Supercritical Emulsion Extraction (SEE) technology. Polymer molecular weight, co-polymer ratio and surfactant amount in aqueous phases as well as phases mixing rate were varied to fabricate carriers with suitable size and loadings. Carriers with different mean sizes from 0.4 ± 0.09 μm up to 3 ± 0.9 μm were obtained by SEE technology when processing emulsions with different formulations; carriers were loaded with 3 μg/g and 7 μg/g for hGDF-5 and hTGF-β1 with controlled growth factor release over 25 days. Carriers displayed extremely low cytotoxicity when evaluated in Chinese Hamster Ovary cells (CHO-K1). Further, they also exhibited reduced cytotoxicity with respect to carriers obtained by conventional evaporation techniques, and low reactivity on human peripheral blood mononuclear cells (hPBMCs), suggesting their safety and potential use in tissue engineering protocols.


Levels of persistent organic pollutants in pine tree components and ambient air.
Pine needles are employed as alternative biomonitoring agents in atmospheric studies. In this study, pine (Pinus Pinea) components (needles and branches) and air samples were collected simultaneously to monitor polychlorinated biphenyls (PCBs), polycyclic aromatic hydrocarbons (PAHs) and organochlorine pesticides (OCPs) from Gemlik, Turkey between January and December 2016. The relationship between ambient air and pine needles were examined to enlighten the usability of pine components as passive samplers for persistent organic pollutants (POPs) in the Marmara region. Average ∑14PAH concentrations for the ambient air, pine needles, and pine branches were 23.1 ± 18.3 ng/m3, 626 ± 306 ng/g DW and 548 ± 261 ng/g DW respectively. PCB concentrations were 118 ± 74 pg/m3, 7.5 ± 2.1 ng/g DW and 6.8 ± 2.9 ng/g DW and ∑10 OCP concentrations were 122 ± 89 ng/m3,1.3 ± 1.5 ng/g DW and 10.0 ± 3.8 ng/g DW in the same order. Levels of PAHs and PCBs were higher in needles than branches. PAH, PCB and OCP concentrations in pine components tended to decrease with increasing temperatures in spring. PAH compounds with medium and light molecular weighted ones were found to be dominant. On the other hand, the predominant PCB components were the medium-weighted congeners while γ-HCH, Heptachlor endo. Epox. Iso A, endrin aldehyde, and methoxychlor were the dominant OCP species.


PET imaging of brain amyloid in dementia: a review.
To review the rapidly expanding literature of amyloid PET imaging with particular attention to Pittsburgh compound-B (PIB) in Alzheimer's disease (AD), dementia with Lewy bodies (DLB), fronto-temporal dementia (FTD), mild cognitive impairment (MCI) and cognitively normal volunteers. Literature searches were performed using Medline up to February 2010. Individual articles were then examined for additional references not revealed by automated searches. This yielded 79 articles whose abstracts were read by the authors to select key papers. Amyloid deposition assessed using PIB-PET is significantly elevated in AD and DLB compared to controls and those with FTD. In MCI, uptake is often intermediate between AD and normal ageing, and excessive amyloid burden in non-demented individuals with MCI are likely to represent high-risk cases. Amyloid deposition appears to be an early event, and as dementia progresses clinical decline seems to be more associated with neurodegeneration than amyloid burden. PIB-PET imaging is a sensitive and specific marker for underlying Aβ amyloid deposition and represents an important investigative tool for examining the relationship between amyloid burden, clinical symptoms and structural and functional changes in dementia. Amyloid imaging may also be useful for selecting patients for anti-amyloid therapies. However, studies have identified PIB-positive cases in otherwise healthy older individuals (10-30%), limiting diagnostic specificity. Development of biomarkers for investigating other aspects of dementia pathology, i.e. soluble Aβ, tau, synuclein and brain inflammation would further inform our understanding and assist in studying disease-modifying and preventive treatments in dementia.


Therapeutic strategies targeting Wnt/β‑catenin signaling for colorectal cancer (Review).
Colorectal cancer (CRC) is one of the most common carcinomas. Although great progress has been made in recent years, CRC survival remains unsatisfactory due to high metastasis and recurrence. Understanding the underlying molecular mechanisms of CRC tumorigenesis and metastasis has become increasingly important. Recently, aberrant Wnt/β‑catenin signaling has been reported to be strongly associated with CRC tumorigenesis, metastasis and recurrence. Therefore, the Wnt/β‑catenin signaling pathway has potential value as a therapeutic target for CRC. In the present review, the dysregulation of this pathway in CRC and the promoting or suppressing function of therapeutic targets on CRC were explored. In addition, the interaction between this pathway and epithelial‑mesenchymal transition (EMT), cell stemness, mutations, metastasis‑related genes and tumor angiogenesis in CRC cells were also investigated. Numerous studies on this pathway may help identify the potential diagnostic and prognostic markers and therapeutic targets for CRC.


Spatial Eco-Risk Assessment of Heavy Metals in the Surface Soils of Industrial City of Aran-o-Bidgol, Iran.
Heavy metals usually accumulate and migrate in soil environment due to human activities and this in return poses potential ecological and health risks. A total of 135 surface soil samples were collected from Aran-o-Bidgol City, Iran and were analyzed for their Cd, Pb, Ni and Cu concentrations to determine these elements' spatial distribution and potential ecological risks. To this end, interpolation mapping was conducted using Ordinary Kriging. The mean concentrations of Cd, Pb, Ni and Cu in the samples were 0.72, 11.41, 29.87 and 14.82 mg kg(-1), respectively, which were all higher than their background values. The spatial variation in the concentration of heavy metals could be attributable to point sources and vehicle emissions. Considering the severity of the potential ecological risks of metals, the descending order of contaminants' concentrations was Cd > Cu > Ni > Pb. The Potential Ecological Risk Index (RI) suggested that approximately 40 % and 59 % of the samples posed high and significantly high potential ecological risks, respectively. Moreover, ecological risk decreased progressively going from southwest to northeast over the under-study area. Considering the background values and RI, this area presented a relatively high level of contamination.


The Correlation of Malnutrition with Mortality and Morbidity According to Global Initiative on Malnutrition Criteria in the Palliative Care Unit.
The objective of this study was to retrospectively assess the correlation of malnutrition with mortality and morbidity according to Global Initiative on Malnutrition criteria in patients with the diagnosis of lung cancer hospitalized in the palliative care unit. The sample of the study consisted of the data of 705 patients with lung cancer, who were hospitalized in the palliative care unit in a training and research hospital between January 2018 and January 2020. All the patients' demographic characteristics, disease-related data, laboratory values, Global Initiative on Malnutrition scores, mortality in the last 3 months, and recurrent hospitalizations in the last 3 months were recorded from the patient records and automation system. According to the Global Initiative on Malnutrition criteria, 64 (9.2%) of the patients had malnutrition. There was a negative correlation between the ages and the admission albumin levels of patients with malnutrition who passed away in the last 3 months. No correlation was found between malnutrition and duration of mortality according to Global Initiative on Malnutrition criteria. Moreover, a difference was found between C-reactive protein and albumin levels of the patients according to the degree of malnutrition. It is recommended that nurses should start nutritional assessments of patients immediately when the patient is admitted to hospital.


Attitudes versus performance in providing gynecologic care to adolescents by pediatricians.
This study ascertained current pediatric attitudes verses performance in caring for adolescent females in private practices in a suburban area. Sixty-seven randomly selected pediatricians were given a confidential questionnaire; 90% responded. Areas assessed were attitudes and practice about sexual history, breast examination, teaching self-breast examination, and vaginal examination. Comparisons were made between the different age groups and between male and female pediatricians. Ninety-two percent of pediatricians felt it was important to take a sexual history by age 16 years, while only 73% actually did. More female than male pediatricians thought it was important to take a sexual history and actually did so. Seventy-five percent stated that a breast examination should be routine, and most performed the examination. However only 60% taught self-breast examination despite the fact that 93% believed it was important. An internal vaginal examination as part of a routine physical was performed by only 7%. For specific gynecologic problems most asked to see the patient but most did not do an internal examination. The most likely indication for a pelvic examination was a vaginal discharge, but only 28% of the pediatricians would examine their patient for this complaint. Of the pediatricians who do the examination, 41% were not sure they had received the proper training. These data suggest that despite the American Academy of Pediatrics' recommendations that pediatricians continue the care of patients until age 21 years, there does not appear to be optimal care provided to female adolescent patients.


Tissue-specific accumulation and speciation of selenium in rainbow trout (Oncorhynchus mykiss) exposed to elevated dietary selenomethionine.
The toxicity of selenium in fish is influenced by its chemical speciation and the exposure route. In the natural environment, selenium exposure to fish occurs primarily in the form of selenomethionine in diet. Thus, the main objective of this study was to examine the tissue-specific selenium burden and speciation in fish exposed to elevated dietary selenomethionine. Rainbow trout (Oncorhynchus mykiss) were treated with dietary selenomethionine (40 μg g(-1) dry mass) for 2 weeks, and at the end of the exposure different tissue samples were collected to assess the tissue-specific distribution and speciation of selenium. We used synchrotron-based X-ray absorption near edge spectroscopy (XANES) to determine the selenium speciation profile. Selenomethionine, selenocysteine and selenocystine were found to be the predominant form of selenium in all of the tissues; however their relative proportion varied across different tissues. In general, the organs primarily involved in selenium handling in fish (e.g., liver, kidney) accumulated a higher percentage of selenocystine. We also found that dietary selenomethionine exposure resulted into a marked increase in selenium burden of all major tissues in fish including the brain. Collectively, our findings provide new insights into the tissue-specific distribution and speciation of selenium in fish exposed to selenomethionine via diet.


Measuring attentional bias in children with prominent ears: A prospective eye-tracking study.
When observing new faces, most people focus their attention on the central triangle of the face containing the eyes, nose and mouth. When viewing faces with prominent ears, observers may divert their attention from the central triangle. The objective of this study was to determine whether there was an objective attentional bias to prominent ears in comparison to non-prominent ears. A total of 24 naïve participants (13 female; mean age 22.88 years) viewed 15 photographs of children with bilateral prominent ears, unilateral prominent ears and non-prominent ears. Both pre- and post-otoplasty photographs of two patients were included. The eye movements of participants were recorded using the EyeLink 1000, a table-mounted eye-tracking device. Overall, the participants spent more time looking at the ear regions for faces with prominent ears in comparison to faces without prominent ears (p = 0.007, Z = -2.688). The attentional bias to the ear region of the patient who underwent bilateral otoplasty was significantly reduced in the post-operative photograph (p = 0.011, Z = -2.534). The patient who underwent unilateral otoplasty had no significant change in fixation times towards the ear region (p = 0.594, Z = -0.533). This study presents objective data to support the notion that observers show attentional bias to the ear region when viewing faces of children with prominent ears. The scope of this finding requires further research in both extent and impact.


[Orbital floor reconstruction. Comparison of a new perforated 0.15 mm thick PDS layer with established titanium dynamic mesh].
For surgical reconstruction of the orbital floor after blow-out fractures, a new perforated PDS (poly-p-dioxanon) foil (0.15 mm thickness) has recently become available. The main target of this prospective and randomized interdisciplinary clinical study was to compare this new PDS foil with the proven titanium dynamic mesh (0.3 mm thickness). Aside from the common diagnostic procedures, an extensive ophthalmologic examination was performed and documented preoperatively (U1), 4 days (U3), 1 month (U4), and 6 months (U5) postoperatively. In both groups the surgical procedure was tolerated well. The new perforated PDS foil turned out to be easier to handle intraoperatively because of smooth and clean cutting edges. The surgical treatment was well tolerated in all randomized groups. In contrast to the control group, the PDS and TD groups showed postoperatively a slight increase of the preoperative exophthalmos (mean 0.5 mm). The new perforated PDS foil is comparable concerning cosmetic and functional aspects. Especially with regard to stability after blow-out fractures, the new perforated PDS foil is equal to titanium dynamic mesh up to 20 mm in diameter. PDS foil is felt to be superior regarding bioresorption and due to the more convenient handling.


Transverse propagation of action potentials between parallel chains of cardiac muscle and smooth muscle cells in PSpice simulations.
We previously examined transverse propagation of action potentials between 2 and 3 parallel chain of cardiac muscle cells (CMC) simulated using the PSpice program. The present study was done to examine transverse propagation between 5 parallel chains in an expanded model of CMC and smooth muscle cells (SMC). Excitation was transmitted from cell to cell along a strand of 5 cells not connected by low-resistance tunnels (gap-junction connexons). The entire surface membrane of each cell fired nearly simultaneously, and nearly all the propagation time was spent at the cell junctions, the junctional delay time being about 0.3-0.5 ms (CMC) or 0.8-1.6 ms (SMC). A negative cleft potential (Vjc) develops in the narrow junctional clefts, whose magnitude depends on the radial cleft resistance (Rjc), which depolarizes the postjunctional membrane (post-JM) to threshold. Propagation velocity (theta) increased with amplitude of Vjc. Therefore, one mechanism for the transfer of excitation from one cell to the next is by the electric field (EF) that is generated in the junctional cleft when the pre-JM fires. In the present study, 5 parallel stands of 5 cells each (5 x 5 model) were used. With electrical stimulation of the first cell of the first strand (cell A1), propagation rapidly spread down that chain and then jumped to the second strand (B chain), followed by jumping to the third, fourth, and fifth strands (C, D, E chains). The rapidity by which the parallel chains became activated depended on the longitudinal resistance of the narrow extracellular cleft between the parallel strands (Rol2); the higher the Rol2 resistance, the faster the theta. The transverse resistance of the cleft (Ror2) had almost no effect. Increasing Rjc decreases the total propagation time (TPT) over the 25-cell network. When the first cell of the third strand (cell C1) was stimulated, propagation spread down the C chain and jumped to the other two strands (B and D) nearly simultaneously. Transverse propagation of excitation occurred at multiple points along the chain as longitudinal propagation was occurring, causing the APs in the contiguous chains to become bunched up. Transverse propagation was more erratic and labile in SMC compared to CMC. Transverse transmission of excitation did not require low-resistance connections between the chains, but instead depended on the value of Rol2. The tighter the packing of the chains facilitated transverse propagation.


Combined Influence of Gestational Weight Gain and Estimated Fetal Weight on Risk Assessment for Small- or Large-for-Gestational-Age Birth Weight: A Prospective Cohort Study.
To evaluate the frequency with which gestational weight gain and estimated fetal weight do not track across gestation and to assess the risk of small-for-gestational-age (SGA) and large-for-gestational-age (LGA) birth weight as a function of tracking. This study included a pregnancy cohort (2009-2013) of 2438 women from 4 racial/ethnic groups in the United States. We calculated race- and trimester-specific gestational weight gain and estimated fetal weight z scores. The prevalence of how often gestational weight gain and estimated fetal weight did not or did directly track was examined by grouping z scores into measure-specific categories (<-1 SD, -1 to + 1 SD, and >1 SD) and then examining 2-measure combinations. Trimester-specific relative risks for SGA and LGA births were estimated with a gestational weight gain and estimated fetal weight z score interaction. We estimated coefficients for selected gestational weight gain and estimated fetal weight values (-1 SD, 0 SD, and +1 SD) compared with the referent of 0 SD for both measures. Small and large for gestational age were calculated as birth weight below the 10th and at or above the 90th percentiles, respectively. Gestational weight gain and estimated fetal weight were within 1 SD 55.5%, 51.5%, and 48.2% of the time in the first, second, and third trimesters, respectively. There was no significant interaction between gestational weight gain and estimated fetal weight on the risk of SGA in the first and second trimesters (interaction term P = .48; P = .79). In the third trimester, there was a significant interaction (P = .002), resulting in a 71% (95% confidence interval, 1.45-2.02) increased risk of SGA when estimated fetal weight was low and gestational weight gain was high. These relationships were similar for the risk of LGA. Deviations in either measure, even in the presence of average gestational weight gain or estimated fetal weight, still suggest an increased risk of SGA and LGA.


The effects of graded levels of calorie restriction: VI. Impact of short-term graded calorie restriction on transcriptomic responses of the hypothalamic hunger and circadian signaling pathways.
Food intake and circadian rhythms are regulated by hypothalamic neuropeptides and circulating hormones, which could mediate the anti-ageing effect of calorie restriction (CR). We tested whether these two signaling pathways mediate CR by quantifying hypothalamic transcripts of male C57BL/6 mice exposed to graded levels of CR (10 % to 40 %) for 3 months. We found that the graded CR manipulation resulted in upregulation of core circadian rhythm genes, which correlated negatively with circulating levels of leptin, insulin-like growth factor 1 (IGF-1), insulin, and tumor necrosis factor alpha (TNF-α). In addition, key components in the hunger signaling pathway were expressed in a manner reflecting elevated hunger at greater levels of restriction, and which also correlated negatively with circulating levels of insulin, TNF-α, leptin and IGF-1. Lastly, phenotypes, such as food anticipatory activity and body temperature, were associated with expression levels of both hunger genes and core clock genes. Our results suggest modulation of the hunger and circadian signaling pathways in response to altered levels of circulating hormones, that are themselves downstream of morphological changes resulting from CR treatment, may be important elements in the response to CR, driving some of the key phenotypic outcomes.


Neonatal morbidity in pregnancy complicated by diabetes mellitus: predictive value of maternal glycemic profiles.
The relationship between glycemic control and perinatal outcome was assessed in a relatively uniform population of 75 White Class B through D pregnant diabetic women. All patients used glucose reflectance meter self-monitoring and performed a minimum of four determinations daily. Mean capillary blood glucose was calculated from a minimum of 16 weeks of determinations. Regression analysis confirmed a correlation between these values and third-trimester hemoglobin A1 (p less than 0.001). The study population was divided into two groups on the basis of mean capillary blood glucose values: group I, mean capillary blood glucose less than 110 mg/dl (43 patients) (mean = 96.8 +/- 7.1); group II, mean capillary blood glucose greater than 110 mg/dl (32 patients) (mean = 126 +/- 9.0). Of the 32 patients in group II, eight had mean capillary blood glucose greater than or equal to 130 mg/dl. The degree of maternal glycemic control appeared to affect perinatal outcome. At least one form of infant morbidity was present in 33% of group I infants compared with 53% of group II. Significant differences were observed for the incidence of hypoglycemia (p less than 0.05), macrosomia (p less than 0.05), and respiratory distress syndrome (p less than 0.01). One of six group I infants delivered at 35 to 36 weeks developed respiratory distress syndrome, compared with four of seven group II patients. The appearance of phosphatidylglycerol in amniotic fluid appeared delayed in group II patients at term. These data suggest that maintaining mean capillary blood glucose values less than 110 mg/dl may serve to reduce several major forms of morbidity in the infant of the diabetic mother. This information is helpful in establishing objectives for glycemic control in pregnant women using self-monitoring techniques.


Implementing ecopharmacovigilance in practice: challenges and potential opportunities.
Ecopharmacovigilance (EPV) is a developing science and it is currently very unclear what it might mean in practice. We have performed a comparison between pharmacovigilance (PV) and EPV and have identified that there are similarities, but also some important differences that must be considered before any practical implementation of EPV. The biggest difference and greatest challenge concerns signal detection in the environment and the difficulty of identifying cause and effect. We reflect on the dramatic vulture decline in Asia, which was caused by the veterinary use of diclofenac, versus the relative difficulty in identifying the specific causes of intersex fish in European rivers. We explore what EPV might mean in practice and have identified that there are some practical measures that can be taken to assess environmental risks across product life cycle, particularly after launch of a new drug, to ensure that our risk assessments and scientific understanding of pharmaceuticals in the environment remain scientifically and ecologically relevant. These include: Tracking environmental risks after launch of the product, via literature monitoring for emerging data on exposure and effects Using Environmental Risk Management Plans (ERMPs) as a centralized resource to assess and manage the risks of a drug throughout its life cycle Further research, testing or monitoring in the environment when a risk is identified Keeping a global EPV perspective Increasing transparency and availability of environmental data for medicinal products. These measures will help to ensure that any significant environmental issues associated with pharmaceuticals in the environment (PIE) are identified in a timely way, and can be managed appropriately.


Anesthetic management of a patient with beta-thalassemia intermedia undergoing splenectomy: a case report.
A 37-year-old man with beta-thalassemia intermedia (betaTI), a rare disease caused by partial or complete deficiency of beta-globin chain synthesis, fell into a hemolytic crisis. Severe anemia persisted despite frequent transfusions. Therefore, he was scheduled for splenectomy to alleviate the anemia. The preoperative laboratory data showed marked anemia and liver dysfunction. Echocardiography revealed hyperkinetic left ventricular motion and increased cardiac index (CI), indicating a compensatory hyperdynamic circulation induced by persistent, severe anemia. Our strategy during general anesthesia was to keep the hyperkinetic cardiovascular system steady. Hence, the hemodynamic parameters including the CI were measured using a Swan-Ganz catheter, and other physiological parameters were monitored perioperatively. Anesthesia was maintained with balanced anesthesia: isoflurane at low concentrations and fentanyl to avoid cardiovascular depression. Throughout the operation, vital signs were kept stable and the lactate/pyruvate ratio was unchanged, indicating that anaerobic metabolism did not increase. We report successful anesthetic management with attention to hemodynamic changes in a patient with betaTI.


Religiosity and the Motivation for Social Affiliation.
Although universal, the motivation to affiliate can vary as a function of individual differences and of the characteristics of the target. Three studies explored the extent to which religious beliefs and identity are related to social affiliation motivation. Because most religions advocate affiliation and provide opportunities for frequent experiences of affiliation, we reasoned that religious people might show greater affiliation motivation in everyday attitudes and behaviors. We found that religiosity was positively related to implicit and behavioral measures of general social affiliation (Studies 1 and 2). However, manipulating the identity of the affiliation target revealed that when affiliating might not lead to positive outcomes, the relation between religiosity and social affiliation disappeared (but did not reverse). In Studies 2 and 3, when the target of the affiliation was explicitly identified as a member of a threatening out-group (atheist), religiosity did not predict affiliation behaviors. We discuss the mechanisms by which religiosity motivates and constrains social affiliation and the potential implications for social influence and intergroup processes.


Sensitivity of picroindigocarmine/nuclear fast red (PIC/NF) stain for detection of spermatozoa: a serial dilution study of human ejaculate.
A serial dilution study from human ejaculate was done in order to assess the sensitivity of a commonly employed stain, picroindigocarmine/nuclear fast red, for the detection of spermatozoa. The results of the study indicate that spermatozoa may be detected readily at very low concentrations by scanning 20 high-power fields of a stained smear.


High affinity P2x-purinoceptor binding sites for [35S]-adenosine 5'-O-[3-thiotriphosphate] in rat vas deferens membranes.
1. The binding sites labelled by [35S]-adenosine 5'-O-[3-thiotriphosphate]([35S]-ATP gamma S) at 4 degrees C in rat vas deferens membranes were studied and compared to the sites labelled by [3H]-alpha,beta-methylene ATP ([3H]-alpha beta meATP) to ascertain whether [35S]-ATP gamma S can be used to label the P2x purinoceptor. 2. In the presence of 4 mM CaCl2, the binding of 0.2 nM [35S]-ATP gamma S to vas deferens membranes was increased 3.4 fold, when compared to studies performed in the absence of calcium. However, binding did not appear to be solely to P2x purinoceptors since [35S]-ATP gamma S labelled a heterogeneous population of sites and about 72% of the sites possessed high affinity (pIC50 = 7.5) for guanosine 5'-O-[3-thiotriphosphate] (GTP gamma S). Even in the presence of 1 microM GTP gamma S, to occlude the sites with high affinity for GTP gamma S, the binding of [35S]-ATP gamma S was heterogeneous and since there was also evidence of extensive metabolism of ATP in the presence of calcium, the binding of [35S]-ATP gamma S under these conditions was not studied further. 3. In the absence of calcium ions, [35S]-ATP gamma S bound to a single population of sites (pKD = 9.23; Bmax = 4270 fmol mg-1 protein). Binding reached steady state within 3 h (t1/2 = 38 min), was stable for a further 4 h and was readily reversible upon addition of 10 microM unlabelled ATP gamma S (t1/2 = 45 min). In competition studies the binding of 0.2 nM [35S]-ATP gamma S was inhibited by a number of P2x purinoceptor agonists and antagonists, but not by adenosine receptor agonists, staurosporine (1 microM) or several ATPase inhibitors. The rank order of agonist affinity estimates (pIC50 values) in competing for the [35S]-ATP gamma S binding sites was: ATP (9.01), 2-methylthio- ATP (8.79), ATP gamma S (8.73), alpha beta meATP (7.57), ADP (7.24), beta, gamma-methylene ATP (7.18), L-beta, gamma-methylene ATP (5.83), alpha, beta-methylene ADP (4.36). 4. Affinity estimates (pIC50 values) for the P2x purinoceptor antagonists, suramin (5.20), pyridoxalphosphate-6-azophenyl-2',4'-disulphonic acid (4.23), pyridoxal 5-phosphate (3.42), cibacron blue (5.70) and Evan's blue (5.79) were broadly similar to those obtained at the [3H]-alpha beta meATP binding sites in vas deferens. However, ATP, 2-methylthio-ATP, ATP gamma S and ADP displayed 17-512 fold higher affinity for the [35S]-ATP gamma S, than for the [3H]-alpha beta meATP binding sites, whereas alpha beta meATP and L-beta, gamma-methylene ATP displayed 5 and 28 fold, respectively, higher affinity for the [3H]-alpha beta meATP than for the [35S]-ATP gamma S binding sites. 5. The differences in agonist affinity for the [35S]-ATP gamma S and [3H]-alpha beta meATP binding sites probably reflect the fact that the former sites were labelled in the absence of calcium, while the latter sites were labelled in its presence. This could differentially affect ionisation state and/or metabolism of the nucleotides when using the two radioligands. Since affinity estimates for ATP, 2-methylthio-ATP, ATP gamma S, alpha beta meATP and L-beta, gamma-methylene ATP were different when calcium ions were omitted in studies using [3H]-alpha beta meATP but similar to the affinity estimates obtained at the [35S]-ATP gamma S binding sites labelled in the absence of calcium, it is likely that [35S]-ATP gamma S and [3H]-alpha beta meATP label the same sites in rat vas deferens. 6. We conclude that, in the absence of divalent cations, [35S]-ATP gamma S labels P2x purinoceptors in rat vas deferens and as such may represent a new, high specific activity, radioligand for the study of such receptors.


Development of pullulanase mutants to enhance starch substrate utilization for efficient production of β-CD.
The inhibitory effect of β-CD on pullulanase which hydrolyzes α-1,6 glycosidic bond in starch to release more available linear substrates, limited substrate utilization thus influencing the yield of β-CD. Here, an aspartic acid residue (D465) which interacted with cyclodextrin ligand by hydrogen bond, was mutated to explore its contribution to bind inhibitors and obtain mutants with lower affinity to β-CD. Enzyme activity results showed that mutants D465E and D465N retained higher activity than wild-type pullulanase in presence of 10 mM β-CD. Circular dichroism spectra and fluorescence spectra results showed that D465 was related to structure stability. Chain length distribution results confirmed the improvement of substrate utilization by the addition of D465E. The conversion rate from potato starch, cassava starch, and corn starch into β-CD, increased to 56.9%, 55.4% and 54.7%, respectively, when synchronous using β-CGTase and D465E in the production process.


Stress fractures: a diagnostic problem.
Three cases of stress fracture, in which diagnosis was aided by sequential radiographs and radionuclide scanning are presented; and a procedure for their management, which attempts to eliminate the need for invasive investigations, is suggested.


Nerve injury-induced changes in opioid modulation of wide dynamic range dorsal column nuclei neurones.
In the present study we investigated the effects of spinal morphine on the electrically and naturally evoked responses of gracile nuclei neurones in a rat model of neuropathy, induced by the tight ligation of lumbar L5/6 spinal nerves. Two weeks after surgery, animals were prepared for electrophysiological recordings and neuronal responses were characterised to a range of controlled natural (brush, low- and high-intensity von Frey filaments, heat 45 degrees C) and peripheral electrical stimuli. Morphine (0.1, 0.25, 1 and 5 microg) was applied spinally and its effect was compared to that in sham-operated or naive animals. Following surgery, all neuropathic rats exhibited signs of mechanical allodynia. Nerve injury induced a significant increase in the receptive field size of gracile nuclei neurones, and also produced a non-significant increase in the proportion and level of spontaneous activity in these neurones. The baseline electrical and natural evoked responses remained unaltered. Spinal morphine reduced both the Adelta-fibre- and C-fibre-evoked responses of gracile nuclei neurones, and similarly inhibited the heat-evoked responses of neuropathic, sham-operated and naive rats. Morphine, however, produced only minor reductions (<30% inhibition of pre-drug control responses) of the Abeta-fibre- and brush-evoked responses of gracile nuclei neurones. These drug effects were similar in all animal groups. In complete contrast, morphine produced a marked inhibition of the low-intensity punctate mechanical evoked responses (von Freys 2 and 9 g) after nerve injury, an effect that was totally lacking in the sham-operated or naive animal groups. This dramatic shift was selective for the low-intensity punctate mechanical stimuli and such an effect was not seen with the noxious mechanical punctate stimulus (von Frey 75 g) where there was a modest inhibition in all groups. Our results suggest that there is plasticity in the opioid modulation of dorsal column projection pathways following spinal nerve ligation and these alterations appear to interact with sensory pathways conveying low-threshold punctate stimuli.


[Locally recurrent rectal cancer].
Over the last decades the therapy of rectal carcinoma has shown continuous improvement. Due to improvements in operative techniques, such as the establishment of total mesorectal excision (TME) and the combination of surgery and (neo-) adjuvant radiochemotherapy, the incidence of locally recurrent rectal cancer could be improved from nearly 50% to less then 10%. Nevertheless recurrent rectal carcinoma remains a severe problem. Predictive factors relating to locally recurrent rectal cancer are surgical experience, localization of the tumor, circumferential resection margins, stage-oriented multimodal therapy and a suitable oncological procedure for the primary tumor. In addition the tumor-specific biology also seems to be a relevant risk factor for recurrence. Operative treatment of locally recurrent rectal cancer was seen for a long time as a palliative procedure. Newer data show that resection of locally recurrent rectal cancer can be carried out with a curative intention in experienced institutions with a long-term 5 year survival of about 30% and mortality around 5%. The composite sacropelvic resection technique is a reasonable option in the curative treatment of locally recurrent rectal cancer. For the future the focus must be on improvements in the primary therapy of rectal carcinoma to avoid local recurrence. In addition early diagnosis of local recurrence and multimodal therapies will be of decisive importance.


Effects of Psoroptes ovis (Acarina:Psoroptidae) on certain biochemical constituents of cattle serum.
Sera from Psoroptes ovis-infested calves were examined for 17 selected biochemical constituents to determine if P. ovis caused changes in any of these constituents. In order to recognize a scabies effect, there had to be a statistically significant (P less than or equal to 0.10) scabies exposure X time interaction and the changes in the biochemical constituents should have been correlated with the changes in the mite infestation. Five serum biochemical constituents fulfilled these criteria. Total protein, alpha-, beta-, and gamma-globulin were increased and total cholesterol was decreased at the peak of the scabies infestation. Precipitating antibodies to a P. ovis antigen were detected by immunodiffusion in some of the stored sera of the infested calves just after the peak of the infestation. Total protein, beta-, and gamma-globulin values were probably increased as a result of antibody production; alpha-globulin values were probably increased as a result of inflammation. As the scabies infestation declined, the mean values of all the above constituents from the infested calves, except cholesterol, began declining. Decreases in total cholesterol occurred, but they could not be entirely attributed to scabies. Examination of the serum biochemical constituents from a heavily infested calf that died during the test suggested that, in addition to antibody production and inflammation, kidney and liver damage may have occurred.


A reflection on partial coherence in electron microscopy.
The concept of partial coherence, which originated in light optics, is investigated in the case of dark-field electron microscopy. Two atoms arbitrarily arranged in the object space are considered as sources of the secondary waves. The influence of lens aberrations is taken into account. The real degree of coherence gamma r is calculated for the STEM as well as the CTEM. In the case of atomic resolution, the finite size of the atoms significantly influences the degree of coherence, so that it becomes a function of the image coordinate. Analytical expressions are obtained for gamma r which are valid at present-day resolutions for both the CTEM and STEM. The dark-field intensity distribution in the detector plane of a STEM is calculated for an object consisting of two atoms in different configurations and for different positions of the scanning spot.


Modeling of moral decisions with deep learning.
One example of an artificial intelligence ethical dilemma is the autonomous vehicle situation presented by Massachusetts Institute of Technology researchers in the Moral Machine Experiment. To solve such dilemmas, the MIT researchers used a classic statistical method known as the hierarchical Bayesian (HB) model. This paper builds upon previous work for modeling moral decision making, applies a deep learning method to learn human ethics in this context, and compares it to the HB approach. These methods were tested to predict moral decisions of simulated populations of Moral Machine participants. Overall, test results indicate that deep neural networks can be effective in learning the group morality of a population through observation, and outperform the Bayesian model in the cases of model mismatches.


Efficient labeling of retinal fundus photographs using deep active learning.
To compare the performance of four deep active learning (DAL) approaches to optimize label efficiency for training diabetic retinopathy (DR) classification deep learning models. 88,702 color retinal fundus photographs from 44,351 patients with DR grades from the publicly available EyePACS dataset were used. Four DAL approaches [entropy sampling (ES), Bayesian active learning by disagreement (BALD), core set, and adversarial active learning (ADV)] were compared to conventional naive random sampling. Models were compared at various dataset sizes using Cohen's kappa (CK) and area under the receiver operating characteristic curve on an internal test set of 10,000 images. An independent test set of 3662 fundus photographs was used to assess generalizability. On the internal test set, 3 out of 4 DAL methods resulted in statistically significant performance improvements ( p < 1 × 10 - 4 ) compared to random sampling for multiclass classification, with the largest observed differences in CK ranging from 0.051 for BALD to 0.053 for ES. Improvements in multiclass classification generalized to the independent test set, with the largest differences in CK ranging from 0.126 to 0.135. However, no statistically significant improvements were seen for binary classification. Similar performance was seen across DAL methods, except ADV, which performed similarly to random sampling. Uncertainty-based and feature descriptor-based deep active learning methods outperformed random sampling on both the internal and independent test sets at multiclass classification. However, binary classification performance remained similar across random sampling and active learning methods.


Streptococcus pyogenes pSM19035 requires dynamic assembly of ATP-bound ParA and ParB on parS DNA during plasmid segregation.
The accurate partitioning of Firmicute plasmid pSM19035 at cell division depends on ATP binding and hydrolysis by homodimeric ATPase delta(2) (ParA) and binding of omega(2) (ParB) to its cognate parS DNA. The 1.83 A resolution crystal structure of delta(2) in a complex with non-hydrolyzable ATPgammaS reveals a unique ParA dimer assembly that permits nucleotide exchange without requiring dissociation into monomers. In vitro, delta(2) had minimal ATPase activity in the absence of omega(2) and parS DNA. However, stoichiometric amounts of omega(2) and parS DNA stimulated the delta(2) ATPase activity and mediated plasmid pairing, whereas at high (4:1) omega(2) : delta(2) ratios, stimulation of the ATPase activity was reduced and delta(2) polymerized onto DNA. Stimulation of the delta(2) ATPase activity and its polymerization on DNA required ability of omega(2) to bind parS DNA and its N-terminus. In vivo experiments showed that delta(2) alone associated with the nucleoid, and in the presence of omega(2) and parS DNA, delta(2) oscillated between the nucleoid and the cell poles and formed spiral-like structures. Our studies indicate that the molar omega(2) : delta(2) ratio regulates the polymerization properties of (delta*ATP*Mg(2+))(2) on and depolymerization from parS DNA, thereby controlling the temporal and spatial segregation of pSM19035 before cell division.


13C metabolite tracing reveals glutamine and acetate as critical in vivo fuels for CD8+ T cells.
Infusion of 13C-labeled metabolites provides a gold-standard for understanding the metabolic processes used by T cells during immune responses in vivo. Through infusion of 13C-labeled metabolites (glucose, glutamine, acetate) in Listeria monocytogenes (Lm)-infected mice, we demonstrate that CD8+ T effector (Teff) cells utilize metabolites for specific pathways during specific phases of activation. Highly proliferative early Teff cells in vivo shunt glucose primarily towards nucleotide synthesis and leverage glutamine anaplerosis in the tricarboxylic acid (TCA) cycle to support ATP and de novo pyrimidine synthesis. Additionally, early Teff cells rely on glutamic-oxaloacetic transaminase 1 (Got1)-which regulates de novo aspartate synthesis-for effector cell expansion in vivo. Importantly, Teff cells change fuel preference over the course of infection, switching from glutamine- to acetate-dependent TCA cycle metabolism late in infection. This study provides insights into the dynamics of Teff metabolism, illuminating distinct pathways of fuel consumption associated with Teff cell function in vivo.


Isolation of proteins with kinase activity and related to pp60 src from human cells.
A protein kinase activity (PK) was associated with immunoprecipitates between polypeptides of human lymphoblastoid cells of malignant origin (Raji cell line) or of their normal counterparts ( Priess cell line) and antibodies directed against avian pp60 src or against the carboxyterminal hexapeptide of pp60 src. Therefore, these human cells and Rous Sarcoma Virus (RSV) transformed avian cells share antigenic determinants of pp60 src and, in particular, its carboxyterminal sequence, as well as one of its functions, a protein kinase activity. The protein kinase from Raji cells phosphorylated predominantly tyrosine residues, that from Priess cells threonine residues.


Auditory driven gamma synchrony is associated with cortical thickness in widespread cortical areas.
Gamma synchrony is a fundamental functional property of the cerebral cortex, impaired in multiple neuropsychiatric conditions (i.e. schizophrenia, Alzheimer's disease, stroke etc.). Auditory stimulation in the gamma range allows to drive gamma synchrony of the entire cortical mantle and to estimate the efficiency of the mechanisms sustaining it. As gamma synchrony depends strongly on the interplay between parvalbumin-positive interneurons and pyramidal neurons, we hypothesize an association between cortical thickness and gamma synchrony. To test this hypothesis, we employed a combined magnetoencephalography (MEG) - Magnetic Resonance Imaging (MRI) study. Cortical thickness was estimated from anatomical MRI scans. MEG measurements related to exposure of 40 Hz amplitude modulated tones were projected onto the cortical surface. Two measures of cortical synchrony were considered: (a) inter-trial phase consistency at 40 Hz, providing a vertex-wise estimation of gamma synchronization, and (b) phase-locking values between primary auditory cortices and whole cortical mantle, providing a measure of long-range cortical synchrony. A correlation between cortical thickness and synchronization measures was then calculated for 72 MRI-MEG scans. Both inter-trial phase consistency and phase locking values showed a significant positive correlation with cortical thickness. For inter-trial phase consistency, clusters of strong associations were found in the temporal and frontal lobes, especially in the bilateral auditory and pre-motor cortices. Higher phase-locking values corresponded to higher cortical thickness in the frontal, temporal, occipital and parietal lobes. In healthy subjects, a thicker cortex corresponds to higher gamma synchrony and connectivity in the primary auditory cortex and beyond, likely reflecting underlying cell density involved in gamma circuitries. This result hints towards an involvement of gamma synchrony together with underlying brain structure in brain areas for higher order cognitive functions. This study contributes to the understanding of inherent cortical functional and structural brain properties, which might in turn constitute the basis for the definition of useful biomarkers in patients showing aberrant gamma synchronization.


Calcium channels: unanswered questions.
Despite decades of intensive research, many questions remain unresolved regarding the structure and function of voltage-dependent calcium channels. This review considers some of those questions: Where is the activation gate? Where are the inactivation gates? How are the voltage sensors coupled to the gates? Are bacterial K+ channels good models for the Ca2+ channel pore? Are protein-protein interactions fundamental to Ca2+ channel function? Do voltage-dependent Ca2+ channels regulate basal intracellular Ca2+? Are N and P/Q channels specialized for fast neurotransmitter release?


Methods for Monitoring Endocytosis in Astrocytes.
Endocytosis is a vesicle-based mechanism by which eukaryotic cells internalize extracellular material. There are several types of this universal mechanism linked to different types of endocytosed cargo, including pathogens; therefore, several approaches can be applied. Here, we describe techniques that are applicable to study the internalization of flaviviruses; dextrans; transporters, such as, glutamate transporter vGlut1; and peptidergic signaling molecules, including atrial natriuretic peptide into astrocytes, the most heterogeneous neuroglial cells, which play a key homeostatic role in the central nervous system.


Determination of soil adhesion to plastic surfaces using a radioactive tracer.
A quantitative radiochemical test procedure was developed for investigating soil adhesion on polyvinyl chloride (PVC) model materials containing different plasticizers (DOP and Hexamoll) and commercial flooring materials. A repeatable test procedure was developed, including soiling and cleaning with a Mini Cleanability Tester. Three soils all containing 51Cr emitting gamma radiation were used. The materials were subjected to successive soiling and cleaning cycles in order to generate soil accumulation. The type and amount of plasticizer appeared to affect soil adhesion on plastic model materials.


Astrovirus gastroenteritis in children in Taipei.
A prospective study was initiated to study astroviral infections in Taiwan. A total of 415 stool samples were collected and assayed for astrovirus antigen using an enzyme immunoassay. Twelve (2.9%) stool samples from 12 patients were positive for astrovirus antigen. Most patients (8/12) had watery diarrhea which lasted for 2-6 days. The majority of patients recovered without specific treatment, except for two patients who were treated with antibiotics for possible bacterial infections. One patient developed chronic diarrhea and two episodes were nosocomially acquired. A clustering in the autumn and winter, with a peak in December (5/12), was noted. Growth on Caco-2 cells was performed for four specimens with positive astroviral RT-PCR results, and a characteristic cytopathic effect was observed after 4 days. Astroviral RNA was detected in six stool samples using RT-PCR. Five of six strains were serotype 1 and one strain was serotype 3. Sequence homology among the six strains was between 80.5% and 100%. A higher degree of homology (89.9-100%) was noted in the five strains of serotype 1. A phylogenetic study demonstrated two clusters in our strains and Oxford reference strain types 1 and 2. Our study results provide further information about the prevalence and span of clinical spectra associated with astroviral infections in Taiwan. The current study showed that infection with astroviruses may be an important cause of gastroenteritis, as well as respiratory symptoms, in infants and children in Taipei.


Use of Organ Care System Lung for Single-Lung Transplantation.
The Organ Care System-Lung allows for normothermic lung preservation in double-lung transplantation. Deterioration of the lung bloc may due to a single nonfunctional side, and surgeons need to be aware of this scenario in hopes of preserving the functional side for transplantation.


Development of quantitative structure activity relationships for the binding affinity of methoxypyridinium cations for human acetylcholinesterase.
Among the most toxic substances known are the organophosphorus (OP) compounds used as pesticides and chemical warfare agents. Owing to their high toxicity there is a number of efforts underway to develop effective therapies for OP agent exposure. To date all therapies in use treat inhibited acetylcholinesterase (AChE), but are ineffective for the treatment of inhibited AChE, which has undergone a subsequent hydrolysis process, referred to as aging. Toward developing a therapy for treating victims of OP intoxication in the aged state we have developed Quantitative Structure-Activity Relationships (QSARs) based on the AM1 semiempirical quantum mechanical method using the program, CODESSA (COmprehensive Descriptors for Structural and Statistical Analysis). Using this methodology we obtained a multiple correlation QSAR equation which gave R(2)=0.9359 for a random training set of 38 ligands and R(2)=0.9236 for prediction on a random test set of 9 ligands.


Molecular cloning of the structural gene for porcine thyroid peroxidase.
We have isolated and determined the nucleotide sequence of overlapping cDNA clones, representing the entire structural gene for pig thyroid peroxidase. The protein coding region extends from an ATG residue at base 252 to a termination codon at base 3030, coding for a 100.4-kDa apoprotein of 926 amino acids. The derived amino acid composition agrees well with the experimentally determined amino acid composition of purified pig thyroid peroxidase. Five potential glycosylation sites are present in the protein. Potential membrane spanning regions are present at the amino-terminal end (1-23) and near the carboxyl-terminal end (845-870) of the protein. These data indicate that pig thyroid peroxidase is synthesized as a single polypeptide that is membrane-bound.


Gastrodin Derivatives from Gastrodia elata.
Nine new gastrodin derivatives, including seven p-hydroxybenzyl-modified gastrodin ethers (1-7), 6'-O-acetylgastrodin (8), and 4-[α-D-glucopyranosyl-(1 →6)-β-D-glucopyranosyloxy]benzyl alcohol (9), together with seven known derivatives, were isolated from an aqueous extract of Gastrodia elata ("tian ma") rhizomes. Their structures were determined by spectroscopic and chemical methods as well as single crystal X-ray diffraction. Compounds 1-4, 7, 10, and 11 were also isolated from a reaction mixture by refluxing gastrodin and p-hydroxybenzyl alcohol in H2O. As both gastrodin and p-hydroxybenzyl alcohol exist in the plant, the reaction results provide evidence for the production and increase/decrease of potential effective/toxic components when "tian ma" is decocted solely or together with ingredients in Chinese traditional medicine formulations, though the isolates were inactive in the preliminarily cell-based assays at concentrations of 10 μM. Moreover, using ultra-performance liquid chromatography high-resolution electrospray ionization mass spectrometry (UPLC-HRESIMS), 4, 7, 10, and 11, as well as component variations, were detectable in the freshly prepared extracts of different types of samples, including the freeze-dried fresh G. elata rhizomes.


[Arthroscopy of the temporomandibular joint. A study of 20 patients].
Temporomandibular joint arthoscopy is a new diagnostic and therapeutic modality and its development is in its infancy. The purpose of this article is to describe arthroscopic pathologic findings of the superior joint space.


Seromucinous ovarian tumor A comparison with the rest of ovarian epithelial tumors.
Seromucinous ovarian tumors are rare and not adequately described in the literature and this is especially true for seromucinous carcinomas. To describe histological and clinical features of these tumors in comparison with the rest of ovarian epithelial tumors. Two hundred and forty one (241) ovarian tumors, borderline (n=92) or malignant (n=149), treated surgically without neoadjuvant chemotherapy, were examined. Seromucinous borderline (SMBT) and malignant tumors (SMC) comprised 7.8% (n=7) and 4% (n=6) of all borderline tumors and carcinomas, respectively, studied. Mean age of diagnosis was 63.2 and 68.3years and mean size was 6.4cm and 12cm for SMBT and SMC, respectively. Seromucinous tumors were associated with endometriosis in 23.1% of the cases and they were bilateral in 30.8%. Microscopically, variety in cellular composition, papillary architecture and development into thick walled, occasionally muscular, cysts were the main findings. Medullary/paraovarian/tubal or deeply cortical localization was also characteristic. Stage predicted overall and progression-free survival (p<0.0001 and p=0.03, respectively). Five-year survival was 62% for patients with high grade serous carcinoma, 55% for seromucinous carcinoma, 100% for endometrioid carcinoma, 75% for clear cell carcinoma, and 80% for patients with mucinous carcinoma. Differences were not however statistically significant. Seromucinous tumors have unique features that support their classification as a different entity. Their localization and their often thick fibrous or/and muscular wall provides further evidence for an histogenesis from the secondary Müllerian system or vestigial structures.


RETRACTED: The evaluation of computed tomography scans and ultrasounds in the differential diagnosis of periapical lesions.
Traditionally, the definitive diagnosis of periapical lesion depends on histopathological examination of the tissues, which is impractical in cases planned for nonsurgical treatment. Recently, some authors have used ultrasound with power Doppler and computed tomography in differential diagnosis between a cyst and a granuloma. The aim of this study was to evaluate and compare the use of computed tomography (CT) scan and ultrasound with power Doppler flowmetry in differential diagnosis of periapical lesions. Twelve periapical lesions were imaged with the help of CT scans and ultrasound with color-power Doppler flowmetry. A provisional preoperative diagnosis was made based on history, clinical presentation, and radiographic features. The cases were treated by surgical endodontics. In all 12 cases, the diagnosis with CT scan and ultrasound coincided with the histopathological diagnosis of the lesions. It is proposed that CT scans and ultrasound with power Doppler flowmetry can provide an additional dignostic tool without invasive surgery, where treatment option is nonsurgical.


Measuring passive cervical motion: a study of reliability.
To study the inter- and intraexaminer reliability of assessing passive cervical range of motion. Blind, repeated measures of passive cervical range of motion by two different examiners. Ambulatory outpatient facility in an independent NHS funded chiropractic research institution. Fourteen asymptomatic volunteers, 7 men and 7 women, aged 23-45 years. Measurement of passive cervical range of motion using a strap-on head goniometer by two blinded examiners. Each subject was measured three times with 20-min intervals between each measurement, using a mean-of-five-measurements protocol. Passive cervical range of motion in 6 separate directions of movement from "neutral zero"--right and left lateral flexion, right and left rotation and flexion and extension. The inter- and intraexaminer reliability was evaluated using a paired t test and Pearson's Correlation Coefficient (supplemented by a scatterplot). Intraexaminer reliability was found to be acceptable (Pearson's r = 0.61-0.86), whereas interexaminer reliability was less than acceptable (Pearson's r = 0.29-0.66). Passive cervical range of motion could be measured reliably on different occasions by the same examiner but not by different examiners. It is unclear whether low interexaminer reliability in the present study was because of inherent methodological problems or because of insufficient training of examiners before the study.


Distribution of DSM-II diagnoses in a child psychiatric setting.
While DSM-II contains more diagnostic categories related specifically to children than did the earlier DSM-I, clinical utilization studies of the various categories have not been extensive. The present study reports data on the distribution of diagnoses of childhood disorders and analyzes relationships among several diagnostic categories and subject variables. Results indicate that clinicians are using a wide range of DSM-II diagnoses for childhood disorders, including some which were intended for use with adults as well as those which were designed specifically for children. Transient Situational Disorders and Behavior Disorders are assigned almost equally to two-thirds of the sample. Chi-square analyses revealed a relationship between diagnostic categories and subject variables of age and sex. These data suggest that boys, particularly between the ages of 6 and 13, are more frequently than girls categorized as Behavior Disorder, and that the Transient Situational Disorder category is overutilized for adolescents, both male and female.


The practice of teleneurology in the Philippines during the COVID-19 pandemic.
The practice of teleneurology provided an accessible and safe method of consultation during the COVID-19 pandemic. We aimed to describe the practice of teleneurology among Filipino neurologists and determine the factors affecting its adoption using the unified theory of acceptance and use of technology (UTAUT) model and its constructs, namely performance expectancy, effort expectancy, social influence, and facilitating conditions. This was a cross-sectional survey conducted online last October 2020 involving adult and pediatric neurologists in the Philippines. The internal consistency of the questionnaire adapted from UTAUT model was determined using Cronbach's alpha. We performed logistic regression analysis to determine which constructs of the UTAUT model were significant factors on the intent to practice teleneurology. The study yielded a 28.8% response rate. Among the respondents (n1 = 147), 95.2% (n2 = 140) practiced teleneurology during the pandemic, and 77.6% (n1 = 147) planned to continue it after the pandemic. Teleneurology was mostly done on an outpatient basis on social media platforms via videoconferencing due to easier access for both end-users. The UTAUT model explained 80.9% (95% CI 0.76, 0.86a) of the total variation. Performance expectancy and facilitating conditions affect the intent to use teleneurology. Due to the limited resources and knowledge of its practice, infrastructural support and benefit awareness campaigns would be beneficial to increase its adoption, especially in developing countries.


New generation indirect calorimeters for measuring energy expenditure in the critically ill: a rampant or reticent revolution?
To lower the risk of incorrectly feeding critically ill patients, indirect calorimetry (IC) is proposed as the most ideal method to evaluate energy expenditure and to establish caloric goals. New IC devices are progressively introduced but validation of this new generation remains challenging and arduous.


Early treatment of migraine attacks with triptans: a strategy to enhance outcomes and patient satisfaction?
Treating migraine attacks early with triptans may be more effective than late triptan administration. However, in published studies, the definition of 'early' varied (in terms of time, pain intensity or presence of allodynia) or was unclear. Therefore, clear clinical indications have not been established. Appropriately designed trials to address this issue remain a priority. Early triptan treatment may also have disadvantages, including inadvertent treatment of tension-type headaches and danger of medication overuse. At present, only those migraineurs with rapid pain worsening, high pain recurrence rate and clinical indications of allodynia should be encouraged to take triptans as quickly as possible. This recommendation implies a requirement for patient education and the need to carefully tailor treatment to individual needs.


Recurrent and non-recurrent croup: an epidemiological study.
A community-based study investigating the natural history of recurrent and non-recurrent croup is described. Daily temperature data were collected during 1977-83, in order to analyse seasonal variation and the effect of atmospheric temperature on the number of croup episodes per calendar month. A case-control study of 137 cases--consisting of 75 children with recurrent croup and 45 children with non-recurrent croup--and 236 controls matched by age and sex was also conducted. It aimed to study associations between croup and other selected diseases in the patients and their families. Recurrent croup differed from non-recurrent croup in its natural history in a number of ways. There was a winter and autumn peak in the number of episodes per month. These episodes occurred on days with significantly lower maximum and minimum temperatures. Recurrent croup was significantly associated with a patient history of asthma and wheezy bronchitis and a family history of croup. In contrast, non-recurrent croup showed an autumn peak only, as well as no association with atmospheric temperature or other disease in the patients and their families. This study confirms and extends observations indicating that recurrent croup involves a persistent and inherited airways hyper-reactivity that is triggered by viral and other stimuli, including those related to temperature.


Development, Characterization, and Evaluation of Hepatoprotective Effect of Abutilon indicum and Piper longum Phytosomes.
Evidences from ethnopharmacological practices have shown that combination of Abutilon indicum and Piper longum are traditionally used to treat symptoms of the liver disorder. The hypothesis is phytosomes of a combination of both crude drug extract will be more effective and safe as hepatoprotective agent. Present work is aimed at development and characterization of phytosomes containing ethanolic extract of both drugs to meet the need for better effectiveness and safety. Phytosomes were formulated by using Indena's patented process. Characterization involved following parameters: Particle size determination, percentage yield, entrapment efficiency, differential scanning calorimetry, scanning electron microscope, fourier transform infrared spectroscopy, and high performance thin liquid chromatography. Liver damage was induced in adult Charles foster rats (150 ± 10 g) with CCl4 in olive oil (1:1 v/v, i.p) 1 ml/kg once daily for 7 days. LIV 52 (1 ml/kg per oral [p.o]), ethanolic extract of A. indicum and P. longum combination (100, 200, and 400 mg/kg p.o) and phytosomes (100 mg/kg p.o.) was given 3 days prior to CCl4 administration. Estimation of liver marker enzymes and histopathological studies were done. Result was analyzed by using (analysis of variance) followed by Student-Newman-Keuls test. Combined extract has shown hepatoprotective activity but phytosomal formulation has more potent hepatoprotective effect on CCl4 induced liver toxicity at very low dose comparative to a higher dose of combined extract. Novel approach for herbal drug delivery is more prominent than conventional which improves bioavailability of polar extract and also patient compliance. Standardised ethanolic extract of leaves of abutilon indicum and piper longum fruits by microwave assisted extraction was used for phytosomal complex formation and phytosomal complex was characterised by various parameters and finally the hepatoprotective activity of phytosomes and crude extract was evaluated by different biochemical markers and histopathological study. Abbreviations Used: DSC: Differential scanning calorimetry, SEM: Scanning electron microscope, FTIR: Fourier transform infrared spectroscopy, HPTLC: High performance thin liquid chromatography, p.o: Per oral, A. indicum: Abutilon indicum, P. longum: Piper longum.


Salivary Antioxidant Profile in Patients with Systemic Sclerosis and Periodontitis.
The aim of the present study was to compare periodontal status and antioxidant profile in unstimulated saliva of systemic sclerosis (SSc) patients with periodontitis and systemically healthy periodontitis patients. Twenty patients with established diagnoses of systemic sclerosis and periodontitis (SSc group) and 20 systemically healthy individuals with periodontitis (P group) were enrolled in the study. Clinical periodontal parameters (clinical attachment level (CAL), gingival recession (GR), periodontal probing depth (PPD), and gingival index (GI)) and concentration of uric acid (UA), superoxide dismutase (SOD), and glutathione peroxidase (GPX) in unstimulated saliva samples were assessed. There were significantly higher mean values of CAL (4.8 ± 0.21 mm versus 3.18 ± 0.17 mm; p ≤ 0.001) and GR (1.66 ± 0.90 mm versus 0.46 ± 0.54 mm; p ≤ 0.001) in the SSc group when compared to the P group. Significantly higher level of GPX (p ≤ 0.001) and SOD (p ≤ 0.001) in unstimulated saliva was detected in the SSc group in comparison with the P group. The specific activity of UA did not significantly differ between the two groups (p = 0.083). The results may indicate higher periodontal destruction and antioxidant perturbations in unstimulated saliva of SSc patients with periodontitis compared to systemically healthy periodontitis patients.


Sex-specific acute effect of estrogen on endothelium-derived contracting factor in the renal artery of hypertensive Dahl rats.
To determine whether estrogen rapidly affects endothelium-derived contracting factor (EDCF) in the renal artery of hypertensive Dahl rats, and whether factors other than nitric oxide (NO) contribute to the effect of estrogen. Acute effects of estrogen on the acetylcholine-induced vasomotor responses and on prostaglandin H2/thromboxane A2 mimetic, U46619,-induced contraction were examined in isolated arterial rings. Dahl salt-sensitive male and female rats were fed an 8% NaCl diet for 4 weeks. The blood pressure increased more rapidly and to a greater extent in males than in females. Renal arterial rings were prepared for isometric tension recording. 17beta-Estradiol, but not the biologically less active stereoisomer, 17alpha-estradiol, improved the relaxation response to acetylcholine in renal arteries from females. Estrogen also rapidly decreased the contraction evoked by acetylcholine (10(-6) to approximately 10(-4) mol/l) in renal arteries from females and it was effective at a physiological concentration (10(-9) mol/l) in the presence of Nomega-nitro-l-arginine methyl ester (an NO synthase inhibitor). The estrogen receptor antagonist, ICI 182,780, abolished the effect of estrogen, whereas the cytochrome P450 inhibitor, miconazole, had no effect. The contraction induced by U46619 was also suppressed by estrogen, without any contribution from NO. Estrogen had no effect on either relaxation or contraction responses in renal arteries from males. 17beta-Estradiol antagonizes increases in vascular tone in hypertensive females by enhancing NO-dependent relaxation, and by suppressing EDCF-mediated mechanisms in an NO-independent manner.


Attenuation of Lipopolysaccharide-induced Liver Injury by Bone Marrow Mesenchymal Stem Cells via Inhibiting the NLRP3 Inflammasome and Hepatocyte Pyroptosis.
The transplantation of bone marrow mesenchymal cells (BMSCs) has been shown to be an effective mean for treating sepsis-related organ damage. Pytoptotic cell death, in turn, has recently been identified as a key driver of sepsis-related damage. At present, there are few studies on the effect of BMSC transplantation on pyroptotic cell death. We explored the ability of BMSCs to attenuate hepatic damage in a pyroptosis-related manner in a rat model of lipopolysaccharide (LPS)-induced liver injury. Following injury modeling and BMSC transplantation, we assessed the expression of the NLR family, pyrin domain containing 3 (NLRP3) inflammasome, and key downstream pyroptosis-related signaling molecules. It was found that BMSC transplantation was sufficient to significantly improve rat survival after LPS injection. A significantly reduced expression of the pyroptosis-related proteins NLRP3, caspase-1, IL-1β, and IL-18 in rats that had undergone BMSC transplantation compared to control animals was observed. Notably, this activity was superior to single-agent administration of the NLRP3 inhibitor MCC950. Our data suggest that BMSC transplantation may alleviate LPS-induced hepatic damage by suppressing the activation of the NLRP3 inflammasome and the induction of pyroptotic cell death.


Hyperphagia induced by hypoglycemia in rats is independent of leptin and hypothalamic neuropeptide Y (NPY).
Hypoglycemia causes hyperphagia and weight gain, through unknown peripheral and central signals. We investigated the effect of hypoglycemia on NPY and leptin expression and the ability of leptin to inhibit hypoglycemia-induced hyperphagia. Acute hypoglycemia (60 U/kg SC insulin; n = 8) increased food intake (p < 0.01) compared with controls (n = 8). Insulin- and leptin-treated rats (300 microg/kg IP leptin; n = 8) had reduced hyperphagia (p < 0.05 vs. controls; p < 0.05 vs. insulin alone) and a 15% fall in NPY mRNA levels compared with controls (p < 0.01). Chronic hypoglycemia, (20-60 U/kg/day insulin; n = 8) increased food intake compared with vehicle-treated controls (p < 0.01). Leptin and insulin administration (300 microg/kg/day IP leptin; n = 8) reduced hyperphagia (p < 0.01 vs. controls, p < 0.05 vs. insulin alone), and NPY mRNA fell by 18% vs. controls (p < 0.01). We conclude that hypoglycemia-induced hyperphagia is not mediated by either a fall in leptin or an increase in hypothalamic NPY mRNA. Leptin can inhibit feeding in hyperphagic hypoglycemic rats, and this may partly be attributable to its inhibition of the NPY neurons.


Introduction of double amidoxime group by double post surface modification on poly(vinylbenzyl chloride) beads for higher amounts of organic dyes, As (V) and Cr (VI) removal.
In this study, the synthesis of micron-sized poly(vinylbenzyl chloride) (p(VBC)) beads and subsequent conversion of the reactive chloromethyl groups to double amidoxime group containing moieties by post modification is reported. The prepared beads were characterized by SEM and FT-IR spectroscopy. The amidoximated p(VBC) beads were used as adsorbent for the removal of organic dyes, such as eosin y (EY) and methyl orange (MO), and heavy metals containing complex ions such as dichromate (Cr2O7(2-)) and arsenate (HAsO4(2)(-)) from aqueous media. The effect of the adsorbent dose on the percent removal, the effect of initial concentration of adsorbates on the adsorption rate and their amounts were also investigated. The Langmuir, Freundlich and Temkin adsorption isotherms were applied to the adsorption processes. The results indicated that the adsorption of both dichromate and arsenate ions obeyed the Langmuir adsorption model. Interestingly, it was found that the prepared beads were capable of removing significant amounts of arsenate and dichromate ions from tap and river (Sarıcay, Canakkale-Turkey) water.


Familial amyloidotic polyneuropathy with late-onset and well-preserved autonomic function: a Japanese kindred with novel mutant transthyretin (Ala97 to Gly).
We report the characteristics of one patient and two asymptomatic carriers from a Japanese family with familial amyloidotic polyneuropathy (FAP). The clinical features were somatic sensory and motor neuropathy with well-preserved autonomic function and late onset with slow insidious progression. These symptoms and signs are different from those of type 1 FAP. There were massive amyloid deposits with transthyretin (TTR) in the myocardium and the sural nerve. DNA sequencing of the TTR gene and amino acid sequence analysis of serum TTR revealed a new mutation in which Gly97 was substituted for Ala. We suggest that patients with somatic sensory and motor neuropathy of unknown origin without apparent autonomic dysfunction should be further studied for TTR mutation.


Epidemiological, clinical and oncological outcomes of young patients with laryngeal cancer: a systematic review.
To investigate epidemiological, clinical and oncological outcomes of young patients with laryngeal cancer (LC). PubMed, Scopus and Cochrane Library were searched by three researchers for studies investigating epidemiological, clinical and oncological outcomes of patients with age < 40 years old and LC. The following outcomes were investigated with PRISMA criteria: age; ethnicity; gender; tobacco/alcohol habits; anatomical, pathological, therapeutic and survival features. Authors performed a bias analysis of papers and provided recommendations for future studies. Seventeen papers published between 1982 and 2021 met our inclusion criteria, accounting for 928 patients with age < 40 years (female/male ratio: 2:5). There were on average 54.2 and 45.8% of smokers and drinkers. The tumor location mainly consisted of glottis (70.1%), supraglottis (27.7%) and subglottis (2.2%). Radiation therapy was the main therapeutic strategy used in young adults with LC. The 2-year overall survival ranged from 50 to 100% and depended on tumor stage, treatment, and cohort features. Four studies reported better overall survival in young compared with old adults, while there were no significant differences in three studies. There was an important heterogeneity between studies regarding the inclusion/exclusion criteria, epidemiological, clinical, pathological and treatment. It was suggested that young patients with LC had lower proportion of smokers and drinkers and better overall survival compared with older but both data of the current literature and heterogeneity between studies limit us to draw definitive conclusions.


Prolidase activity in rat brain; developmental, regional and subcellular distribution.
We determined the regional and subcellular distribution of prolidase in rat brain and its changes with development. The most rapid changes in enzyme activity occurred perinatally, with a maximum level of activity 2 days before birth and a minimum 1 day after birth. Of the 7 regions examined, cerebellum had the highest enzyme level, followed by medulla. The lowest levels were found in the hypothalamus in the adult and in the midbrain in the young. Polidase was mainly soluble; over 55% was recovered in the S2fraction, and the rest was released from the particulate fractions by hypotonic shock. Brains of male rats contained a slightly higher level of the enzyme.


Chronic diverticulitis vs. colorectal cancer: findings on CT colonography.
The purpose of this update article is to evaluate findings on CT colonography in patients with chronic diverticulitis and to compare the findings in patients with colorectal carcinoma. Different morphological criteria retrieved from a literature review were retrospectively analyzed in a series of 13 patients with proven chronic diverticulitis. The findings were compared with a series of 10 patients with colorectal carcinoma. Overall, the findings in chronic diverticulitis resemble the findings in acute diverticulitis. The advantage of virtual CT colonography in differentiating both entities relies in the combination of morphological features previously described on axial computed tomography and double contrast barium enema. The single strongest morphological feature pointing towards the diagnosis of chronic diverticulitis is the presence of diverticula in the affected segment. In the presence of diverticula in the affected segment, a long segment (≥10 cm), thick fascia sign without adenopathies, mild bowel wall thickening, tapered margins, and distorted but preserved mucosal folds are likely to further improve accuracy of diagnosing chronic diverticulitis. The single strongest morphological sign to differentiate chronic diverticulitis from colorectal cancer is the presence of diverticula in the affected segment.


Interpretation of cutaneous pressure threshold (Semmes-Weinstein monofilament measurement) following median nerve repair and sensory reeducation in the adult.
Semmes-Weinstein nylon monofilaments are used to evaluate recovery of cutaneous pressure threshold in adults recovering from median nerve repair at the wrist level. Of the 46 patients studied, 22 received a program of sensory reeducation. The nylon monofilament measurements accurately described the improvement in recovered sensation following nerve repair. There was a statistically significant better recovery (lower threshold) in patients receiving sensory reeducation, which was present in those less than 30 years old (P less than .003) as well as those greater than 30 years old (P less than .05). However, normal thresholds were not recovered in these patient populations.


Failure of prostacyclin effect on the reversal of early ultrastructural changes in cell nuclei of adrenal cortex after complete 15-min cerebral ischemia in rabbit.
The experiment was carried out on 18 rabbits in two experimental groups. Group I: animals with complete 15-min cerebral ischemia infused with PGI2 for 3 min before, during and for 15-min after ischemia. Group II = control: animals with complete 15 min cerebral ischemia. In both groups, cell nuclei of the adrenal cortex were examined. In the 3rd and 6th h after ischemia numerous vesicular structures, intranuclear filaments and granulofibrillar bodies were found in the nuclei. The vesicular structures were enclosed in a single smooth membrane, some combined with the nuclear envelope, others remained independent. Amassing in karyoplasm of vesicular structures, intranuclear filaments and granulofibrillar bodies probably leads to death of the adrenal cortex cell after complete cerebral ischemia. It is suggested that vesicular structures may form as the result of disturbances in the water-electrolyte exchange between cytoplasm and karyoplasm of adrenal cells. In the experimental conditions, PGI2 did not affect the development of irreversible ultrastructural changes in adrenal cortex cell nuclei after complete prolonged cerebral ischemia.


Feedback linearization based control of a variable air volume air conditioning system for cooling applications.
Design of a nonlinear control system for a Variable Air Volume Air Conditioning (VAVAC) plant through feedback linearization is presented in this article. VAVAC systems attempt to reduce building energy consumption while maintaining the primary role of air conditioning. The temperature of the space is maintained at a constant level by establishing a balance between the cooling load generated in the space and the air supply delivered to meet the load. The dynamic model of a VAVAC plant is derived and formulated as a MIMO bilinear system. Feedback linearization is applied for decoupling and linearization of the nonlinear model. Simulation results for a laboratory scale plant are presented to demonstrate the potential of keeping comfort and maintaining energy optimal performance by this methodology. Results obtained with a conventional PI controller and a feedback linearizing controller are compared and the superiority of the proposed approach is clearly established.


Seasonal occurrence and risk assessment of endocrine-disrupting compounds in Tagus estuary biota (NE Atlantic Ocean coast).
Estuaries are continually threatened by anthropogenic pressures, consequently, a large group of contaminants harmful to human health affects the aquatic biota; therefore, it is necessary to monitor their quality. This study deals with the determination of a large group of compounds representing different endocrine-disrupting compounds (EDCs) classes [21 pesticides, 4 polycyclic musk fragrances, 4 UV-filters, 7 bisphenols, 6 polybrominated diphenyl ethers (PBDEs) and 8 of their methoxylated (MeO-BDEs)] in several estuarine species (fish, bivalves, crustaceans, earthworm, and macroalgae) collected seasonally along one year in two distinct areas of Tagus River estuary ("contaminated" vs. "clean" areas). The most abundant compounds found were galaxolide (HHCB) (81% positive samples; 0.04-74 ng/g ww), isoamyl 4-methoxycinnamate (IMC) (64%; 1.13-251 ng/g ww), alachlor (44%; 0.08-16 ng/g ww), and BDE-47 (36%; 0.06-2.26 ng/g ww). Polycyclic musks were the most frequent contaminants in fish (seabass, barbus, mullet, and sole) and macroalgae samples, while UV-filters were predominant in bivalves and crustaceans, and bisphenols in earthworms. Seasonal variation was verified for Σpesticides and Σmusks, with significantly higher levels in summer and autumn, whereas ΣUV-filters highest levels were found in spring and summer, and for ΣPBDEs statistically higher levels were registered in cold seasons (autumn and winter). Σbisphenols were significantly lower in spring than in the other seasons. In general, considering all species analysed in both areas, no statistically significant differences (p > 0.05) were verified between the two collection areas. Based on the estimated daily intake data, consumption of fish from this estuary is unlikely to be a human health concern, since the levels of contamination were below the toxicological threshold values. Overall, the data obtained in this study will allow regulatory authorities to identify and prioritize contaminants monitoring programs in estuaries, such as the case of bisphenol A, which was found, for the first time, in earthworm and clam species.


[Painless course of chronic calcificated pancreatitis manifesting as hyperglycemia].
The clinical case of chronic calcifying pancreas (CCP) was described. It was reveal that obligate sign CCP as a painful syndrome can disappeared in some circumstances, in particular when the patient refused of smoking and alcohol intake.


Studies on the anti-obesity activity of zinc-α2-glycoprotein in the rat.
To investigate the anti-obesity effect of the adipokine zinc-α(2)-glycoprotein (ZAG) in rats and the mechanism of this effect. Mature male Wistar rats (540 ± 83 g) were administered human recombinant ZAG (50 μg per 100 g body weight given intravenously daily) for 10 days, while control animals received an equal volume of phosphate-buffered saline (PBS). Animals treated with ZAG showed a progressive decrease in body weight, without a decrease in food and water intake, but with a 0.4 °C rise in body temperature. Body composition analysis showed loss of adipose tissue, but an increase in lean body mass. The loss of fat was due to an increase in lipolysis as shown by a 50% elevation of plasma glycerol, accompanied by increased utilization of non-esterified fatty acids, as evidenced by the 55% decrease in plasma levels. Plasma levels of glucose and triglycerides were also reduced by 36-37% and there was increased expression of the glucose transporter 4 in both skeletal muscle and adipose tissue. Expression of the lipolytic enzymes adipose triglyceride lipase and hormone-sensitive lipase in the white adipose tissue (WAT) were increased twofold after ZAG administration. There was almost a twofold increased expression of uncoupling proteins 1 and 3 in brown adipose tissue and WAT, which would contribute to increased substrate utilization. Administration of ZAG increased ZAG expression twofold in the gastrocnemius muscle, BAT and WAT, which was probably necessary for its biological effect. These results show that ZAG produces increased lipid mobilization and utilization in the rat.