Assessment of the potential health risks of heavy metals in soils in a coastal industrial region of the Yangtze River Delta.
Soil heavy metal contamination is a serious environmental problem. Human beings may be directly exposed to heavy metals in soils through the inhalation of soil particles, dermal contact, and oral ingestion, which can seriously threaten health. This study assesses the health risks associated with heavy metals in soils by determining the concentrations of eight heavy metals (Cr, Pb, Cd, Hg, As, Cu, Zn, and Ni) based on 2051 surface-soil samples collected from the southern Yangtze River Delta of China. The mean concentrations were higher than the corresponding background values in Zhejiang Province and China as a whole, indicating an accumulation of heavy metals. The health risk assessment suggests that the non-carcinogenic and carcinogenic risks in the study area were not significant. The non-carcinogenic risk for children was the highest, followed by those for adults and seniors; the non-carcinogenic risk for the entire population was less than 1.0, the predetermined threshold. Carcinogenic risk for adults was the highest, followed by those for seniors and children; a few sample points had a value larger than the threshold of 1.0E-04. Arsenic represented the greatest contribution to non-carcinogenic and carcinogenic risk. Meanwhile, ingestion of heavy metals in soil was the main exposure pathway for carcinogenic risk, followed by inhalation and dermal exposure. The spatial method of Getis-Ord was used to identify hot spots of health risk. Hot spots with high hazard index (HI) and total carcinogenic risk (TCR) for children, adults, and seniors were mainly distributed in core urban areas, such as Jiangbei, Haishu, Yinzhou, Jiangdong, and the urban areas of some other counties, which coincided with industrial, mining, and urban areas of the study area and were strongly influenced by anthropogenic activities. These results provide a basis for heavy metal control in soil, source identification, and environment management in the Yangtze River Delta and other rapidly developing industrial regions in China.


Intergroup conflict: origins, dynamics and consequences across taxa.
Although uniquely destructive and wasteful, intergroup conflict and warfare are not confined to humans. They are seen across a range of group-living species, from social insects, fishes and birds to mammals, including nonhuman primates. With its unique collection of theory, research and review contributions from biology, anthropology and economics, this theme issue provides novel insights into intergroup conflict across taxa. Here, we introduce and organize this theme issue on the origins and consequences of intergroup conflict. We provide a coherent framework by modelling intergroup conflicts as multi-level games of strategy in which individuals within groups cooperate to compete with (individuals in) other groups for scarce resources, such as territory, food, mating opportunities, power and influence. Within this framework, we identify cross-species mechanisms and consequences of (participating in) intergroup conflict. We conclude by highlighting crosscutting innovations in the study of intergroup conflict set forth by individual contributions. These include, among others, insights on how within-group heterogeneities and leadership relate to group conflict, how intergroup conflict shapes social organization and how climate change and environmental degradation transition intergroup relations from peaceful coexistence to violent conflict. This article is part of the theme issue 'Intergroup conflict across taxa'.


Metaphase yields from staphylococcal enterotoxin A stimulated peripheral blood lymphocytes of unirradiated and irradiated aged rhesus monkeys.
The mitogen phytohemagglutinin (PHA) works well in both human and cynomolgus monkey (Macaca fascicularis) lymphocyte cultures to stimulate T cell proliferation. T cells from rhesus monkeys (Macaca mulatta) are less responsive than human cells, producing few metaphases when thousands are required, e.g. in biological dosimetry studies. We show that staphylococcal enterotoxin A (SEA), one of the most potent mitogens known, at a concentration of 0.5 microgram/ml stimulated peripheral lymphocytes to grow with a mitotic index (MI) averaging 0.13 metaphases/cell in old, irradiated rhesus macaques. This was significantly greater (p < 0.001) than that produced by PHA (MI < 0.01) in lymphocytes from the same animals. Whole blood was cultured for 96, 120 and 144 h for five irradiated individuals and for two controls. All cells cultured with SEA produced a high MI with a peak response at 120 h whereas the same cultures showed low MI for each PHA stimulated culture.


Phylogenetic analysis of rabies surveillance samples from north and northeast Brazil.
Viruses of the Lyssavirus genus are classified into several genotypes (GT1 to GT7), of which only GT1 (classic rabies virus-RABV) has a cosmopolitan distribution and circulates in Brazil. GT1 is subdivided into several antigenic variants (AgV) maintained in independent cycles with a narrow host range and distinct geographic distributions, namely, AgV1 and AgV2 found in dogs, AgV3 in the vampire bats Desmodus rotundus, and AgV4 and AgV6 in bats non-hematophagous Tadarida brasiliensis and Lasiurus cinereus, a common variant of marmoset (Callithrix jacchus), and crab-eating fox (Cerdocyon thous). In this study, we performed phylogenetic analysis to identify at the antigenic variant level; six RABV genomes derived from the Rabies Surveillance in the north and northeast regions of Brazil. The analysis resulted in the formation of 11 monophyletic clusters, each corresponding to a particular variant, with high bootstrap support values. The samples were positioned inside the AgV3, AgV6, and Callithrix variant clades. This is the first report of the AgV6 variant found in northern Brazil, which provides valuable information for rabies surveillance in the country. The possibility of viral spillover has been much debated, as it deals with the risk of shifting transmission from a primary to a secondary host. However, more genomic surveillance studies should be performed, with a greater number and diversity of samples to better understand the transmission dynamics of each variant to detect changes in its geographic distribution and spillover events.


The Use of Machine Learning Approaches for the Diagnosis of Acute Appendicitis.
Acute appendicitis is one of the most common emergency diseases in general surgery clinics. It is more common, especially between the ages of 10 and 30 years. Additionally, approximately 7% of the entire population is diagnosed with acute appendicitis at some time in their lives and requires surgery. The study aims to develop an easy, fast, and accurate estimation method for early acute appendicitis diagnosis using machine learning algorithms. Retrospective clinical records were analyzed with predictive data mining models. The predictive success of the models obtained by various machine learning algorithms was compared. A total of 595 clinical records were used in the study, including 348 males (58.49%) and 247 females (41.51%). It was found that the gradient boosted trees algorithm achieves the best success with an accurate prediction success of 95.31%. In this study, an estimation method based on machine learning was developed to identify individuals with acute appendicitis. It is thought that this method will benefit patients with signs of appendicitis, especially in emergency departments in hospitals.


Leukocyte differentials. Are they worth the effort?
This article explores the analytical inaccuracies of routinely performed leukocyte differentials and cites the known biologic and personal physiologic variability in the total leukocyte counts and the leukocyte differential. The clinical value of leukocyte differentials in patients without hematologic disease is assessed on the basis of reports in the existing medical literature. It is concluded that the 100- or 200-cell differential is of no value in the majority of patients on whom the test is requested and that an initial scan of 300 or more cells in concert with the 10,000-cell differentials now available from instruments will soon replace the traditional " diff ".


Cancers in Australia in 2010 attributable to the consumption of alcohol.
To estimate the proportion and numbers of cancers occurring in Australia in 2010 that are attributable to alcohol consumption. We estimated the population attributable fraction (PAF) of cancers causally associated with alcohol consumption using standard formulae incorporating prevalence of alcohol consumption and relative risks associated with consumption and cancer. We also estimated the proportion change in cancer incidence (potential impact fraction [PIF]) that might have occurred under the hypothetical scenario that an intervention reduced alcohol consumption, so that no-one drank >2 drinks/day. An estimated 3,208 cancers (2.8% of all cancers) occurring in Australian adults in 2010 could be attributed to alcohol consumption. The greatest numbers were for cancers of the colon (868) and female breast cancer (830). The highest PAFs were for squamous cell carcinomas of the oral cavity/pharynx (31%) and oesophagus (25%). The incidence of alcohol-associated cancer types could have been reduced by 1,442 cases (4.3%)--from 33,537 to 32,083--if no Australian adult consumed >2 drinks/day. More than 3,000 cancers were attributable to alcohol consumption and thus were potentially preventable. Strategies that limit alcohol consumption to guideline levels could prevent a large number of cancers in Australian adults.


Effects of reinnervation upon electrical membrane properties of normal and paralyzed muscles.
Resting membrane potentials (RMP) and resistance to tetrodotoxin (TTX) have been compared in denervated rat soleus muscles and muscles reinnervated with tetrodotoxin-inactive nerves for periods of 15-18 days. RMP's of the two muscle groups exhibited the same low values typical of denervated muscles. Similarly, comparable values of TTX-resistance were found in the two muscle groups, although exceptions with slightly lower values in the innervated-paralyzed muscles were noted. It is concluded that muscle reinnervation restores to normal the membrane properties altered by denervation essentially through the return of muscle activity.


Stability of cognitive development during the first five years of life in relation to heavy metal concentrations in umbilical cord blood: Mothers' and Children's Environmental Health (MOCEH) birth cohort study.
The objective of this study was to investigate stability of cognitive development during the first five years of life in relation to heavy metal concentrations in umbilical cord blood in Korean children. This research is part of the Mothers' and Children's Environmental Health (MOCEH) study, a multi-center prospective birth cohort study of pregnant women in Korea who were recruited from 2006 to 2010. We analyzed the complete follow-up data of children who were 5years-old in 2016. We measured lead, mercury, and cadmium levels in the umbilical cord blood of 251 children, and analyzed them, for whom neurodevelopmental data were available. We determined stability of cognitive development scores using three methods. First, we used partial correlation analyses to examine the stability of cognitive development at each measurement time. Second, we used Cramer's V to investigate the magnitude and direction of changes in cognitive development scores at each follow-up period among three groups (high, medium, and low scores). The results showed that cognitive development scores measured at the closest times had the strongest correlations, and the stability of cognitive development scores increased with age, from 6 to 60months. Groups at the extreme ends of cognitive development (high or low scores) had more stable scores, and this tendency was also stronger in infants >24months-old. The stability of cognitive development was unrelated to the umbilical cord level of heavy metals, based on analysis with Fisher's transformation. In conclusion, the present study showed that the cognitive development scores in a cohort of infants (6 to 60months-old) were stable.


Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study.
A national cooperative group trial was conducted in patients with early-stage cutaneous malignant melanoma to determine if oral vitamin A can increase disease-free survival or survival. Two hundred forty-eight patients with completely resected melanoma of Breslow's thickness greater than 0.75 mm and clinically negative lymph nodes were randomized to oral vitamin A (100,000 IU/d) for 18 months or to observation. Patients were stratified by Breslow's thickness of primary lesion (0.76 to 1.50 mm, 1.51 to 3.00 mm, or > 3.00 mm), sex, and type of therapy (excision, excision plus node dissection, excision plus perfusion, or excision plus both). The median duration of follow-up observation of living patients is greater than 8 years. The relative risk (RR) in disease-free survival and overall survival in the treatment compared with the observation group was calculated using Cox proportional hazards models. Overall, there was no difference in disease-free survival or overall survival between the two groups. Examination of treatment by stratification interactions and subset analysis did not show any treatment-effect differences based on sex or type of therapy. There was also no difference between groups in disease-free survival based on Breslow's thickness of the primary lesion. Overall, 12% of patients who received vitamin A experienced grade 3 or 4 toxicities. Based on the lack of overall survival benefit, further evaluation of vitamin A as adjuvant therapy for melanoma does not appear warranted.


Low-Frequency Repetitive Transcranial Magnetic Stimulation for Chronic Tension-Type Headache: A Randomized Controlled Study.
Nearly 1-3% of the population is affected by chronic tension-type headaches (CTTH). However, it is still difficult to treat owing to the lack of knowledge of the disease's pathophysiology. Available literature suggests a role for pericranial muscle activity and abnormal modulation of central pain. Repetitive transcranial magnetic stimulation (rTMS) therapy done at the dorsolateral prefrontal cortex (DLPFC) can help modulate pericranial muscle overactivity and central pain modulation in subjects with CTTH. This randomized controlled study aimed to assess the effect of rTMS used in the low-frequency dorsolateral prefrontal cortex on pain and muscle activity in subjects with a chronic tension-type headache. The present randomized controlled clinical study was commenced in a health care center on 20 subjects with chronic tension-type headaches who were given either sham or low-frequency repetitive transcranial magnetic stimulation at the right dorsolateral prefrontal cortex. The therapy effect was evaluated statistically using Welch's corrected t-test. The study results depicted that daily use of rTMS therapy for two weeks led to a considerable reduction in the intensity of the pain, the activity of pericranial muscles, and headache impact, along with an increase in the nociceptive excitability thresholds in subjects with CTTH, with p=0.001 compared to the sham group. Considering its limitations, the present study depicts that rTMS is an efficacious management tool for reducing pain associated with CTTH and can serve as the cornerstone for additional investigations.


Biocompatibility of poly(D,L-lactic-co-hydroxymethyl glycolic acid) microspheres after subcutaneous and subcapsular renal injection.
Poly(D,L-lactic-co-hydroxymethyl glycolic acid) (PLHMGA) is a biodegradable copolymer with potential as a novel carrier in polymeric drug delivery systems. In this study, the biocompatibility of PLHMGA microspheres (PLHMGA-ms) was investigated both in vitro in three different cell types (PK-84, HK-2 and PTECs) and in vivo at two implantation sites (by subcutaneous and subcapsular renal injection) in rats. Both monodisperse (narrow size distribution) and polydisperse PLHMGA-ms were prepared with volume weight mean diameter of 34 and 17 μm, respectively. Mono and polydisperse PLHMGA-ms showed good cytocompatibility properties upon 72 h incubation with the cells (100 μg microspheres/600 μL/cell line). A mild foreign body reaction was seen shortly after subcutaneous injection (20 mg per pocket) of both mono and polydisperse PLHMGA-ms with the presence of mainly macrophages, few foreign body giant cells and myofibroblasts. This transient inflammatory reaction diminished within 28 days after injection, the time-point at which the microspheres were degraded. The degradation profile is comparable to the in vitro degradation time of the microspheres (i.e., within 35 days) when incubated at 37 °C in phosphate buffered saline. Subcapsular renal injection of monodisperse PLHMGA-ms (10 mg) in rats was characterized with similar inflammatory patterns compared to the subcutaneous injection. No cortical damage was observed in the injected kidneys. In conclusion, this study demonstrates that PLHMGA-ms are well tolerated after in vivo injection in rats. This makes them a good candidate for controlled delivery systems of low-molecular weight drugs as well as protein biopharmaceuticals.


Myosin heavy chain expression in renal afferent and efferent arterioles: relationship to contractile kinetics and function.
The physiological role of smooth muscle myosin heavy chain (MHC) isoform diversity is poorly understood. The expression of MHC-B, which contains an insert at the ATP binding pocket, has been linked to enhanced contractile kinetics. We recently reported that the renal afferent arteriole exhibits an unusually rapid myogenic response and that its kinetic features allow this vessel to modulate tone in response to alterations in systolic blood pressure. In the present study, we examined MHC expression patterns in renal afferent and efferent arterioles. These two vessels regulate glomerular inflow and outflow resistances and control the pressure within the intervening glomerular capillaries (PGC). Whereas the afferent arteriole must respond rapidly to increases in blood pressure, the efferent arteriole plays a distinctly different role, maintaining a tonic elevation in outflow resistance to preserve function when renal perfusion is compromised. Using RT-PCR, Western analysis, and immunofluorescence imaging of intact isolated arterioles, we found that the afferent arteriole predominantly expresses the MHC-B isoform, whereas the efferent arteriole expresses only the slower-cycling MHC-A isoform. We examined the kinetics of angiotensin II- and norepinephrine-induced vasoconstriction and found that the afferent arteriole responds approximately 3-fold faster than the efferent arteriole. Our findings thus point to the renal microcirculation as a unique and important example of smooth muscle adaptation in regard to MHC isoform expression and physiological function.


Identification and QTL mapping of whitefly resistance components in Solanum galapagense.
Solanum galapagense is closely related to the cultivated tomato and can show a very good resistance towards whitefly. A segregating population resulting from a cross between the cultivated tomato and a whitefly resistant S. galapagense was created and used for mapping whitefly resistance and related traits, which made it possible to study the genetic basis of the resistance. Quantitative trait loci (QTL) for adult survival co-localized with type IV trichome characteristics (presence, density, gland longevity and gland size). A major QTL (Wf-1) was found for adult survival and trichome characters on Chromosome 2. This QTL explained 54.1 % of the variation in adult survival and 81.5 % of the occurrence of type IV trichomes. A minor QTL (Wf-2) for adult survival and trichome characters was identified on Chromosome 9. The major QTL was confirmed in F3 populations. Comprehensive metabolomics, based on GCMS profiling, revealed that 16 metabolites segregating in the F2 mapping population were associated with Wf-1 and/or Wf-2. Analysis of the 10 most resistant and susceptible F2 genotypes by LCMS showed that several acyl sugars were present in significantly higher concentration in the whitefly resistant genotypes, suggesting a role for these components in the resistance as well. Our results show that whitefly resistance in S. galapagense seems to inherit relatively simple compared to whitefly resistance from other sources and this offers great prospects for resistance breeding as well as elucidating the underlying molecular mechanism(s) of the resistance.


The leading-edge vortex over a swift-like high-aspect-ratio wing with nonlinear swept-back geometry.
The leading-edge vortex (LEV) is a common flow structure that forms over wings at high angles of attack. Over the years, LEVs were exploited for augmenting the lift of man-made slender delta wings aircraft. However, recent observations suggested that natural flyers with high-aspect-ratio (high-AR) wings, such as the common swift (Apus apus), can also generate LEVs while gliding. We hypothesize that the planform shape and nonlinear sweep (increasing towards the wingtip) enable the formation and control of such LEVs. In this paper, we investigate whether a stationary LEV can form over a nonlinear swept-back high-AR wing inspired by the swift's wing shape and evaluate its characteristics and potential aerodynamic benefit. Particle image velocimetry (PIV) measurements were performed in a water flume on a high-AR swept-back wing inspired by the swift wing. Experiments were performed at four spanwise sections and a range of angles of attack for a chord-based Reynolds number of20000. Stationary LEV structures were identified across the wingspan by utilizing the proper orthogonal decomposition (POD) method for angles of attack of 5∘-15∘. The size and circulation of the stationary LEV were found to grow towards the wingtip in a nonlinear manner due to shear layer feeding and spanwise transport of mass and vorticity within the LEV, thus confirming that nonlinear high-AR swept-back wings can generate stationary LEVs. Our results suggest that the common swift can generate stationary LEVs over its swept-back wings to glide slower and at a higher rate of descent, with the LEVs potentially supporting up to 60% of its weight.


Arsenic transfer and impacts on snails exposed to stabilized and untreated As-contaminated soils.
An As-contaminated soil (Unt) was amended with either iron grit (Z), a coal fly ash (beringite, B) or B + Z (BZ) and placed in lysimeters in 1997. An uncontaminated soil (R) was also studied. In summer and autumn 2003, lettuces were cultivated in the lysimeters and snails were caged for one month. Lettuce As concentrations were higher during the summer, while no differences occurred in snails between seasons. Snail As concentrations (microg g(-1) DW) ranged from 2.5 to 7.0 in B, Z and BZ, and peaked at 17.5 in Unt. In summer, snail survival was affected in Unt and Z compared to R and B while no mortality was noticed in autumn. Snail growth decreased only in B, BZ and Unt in autumn. Snail As concentrations suggest a risk for their predators even on the remediated soils.


A comparison of interview methods to ascertain fluoroquinolone exposure before tuberculosis diagnosis.
SUMMARY Fluoroquinolone use before tuberculosis (TB) diagnosis delays the time to diagnosis and treatment, and increases the risk of fluoroquinolone-resistant TB and death. Ascertainment of fluoroquinolone exposure could identify such high-risk patients. We compared four methods of ascertaining fluoroquinolone exposure in the 6 months prior to TB diagnosis in culture-confirmed TB patients in Tennessee from January 2007 to December 2009. The four methods included a simple questionnaire administered to all TB suspects by health department personnel (FQ-Form), an in-home interview conducted by research staff, outpatient and inpatient medical record review, and TennCare pharmacy database review. Of 177 TB patients included, 72 (41%) received fluoroquinolones during the 6 months before TB diagnosis. Fluoroquinolone exposure determined by review of inpatient and outpatient medical records was considered the gold standard for comparison. The FQ-Form had 61% [95% confidence interval (CI) 48-73] sensitivity and 93% (95% CI 85-98) specificity (agreement 79%, kappa = 0.56) while the in-home interview had 28% (95% CI 18-40) sensitivity and 99% (94-100%) specificity (agreement 68%, kappa = 0.29). A simple questionnaire administered by health department personnel identified fluoroquinolone exposure before TB diagnosis with moderate reliability.


CD4 and MHC class 1 down-modulation activities of nef alleles from brain- and lymphoid tissue-derived primary HIV-1 isolates.
Human immunodeficiency virus type 1 (HIV-1) nef undergoes adaptive evolution in the central nervous system (CNS), reflecting altered requirements for HIV-1 replication in macrophages/microglia and brain-specific immune selection pressures. The role of Nef in HIV-1 neurotropism and pathogenesis of HIV-associated dementia (HAD) is unclear. In this study, we characterized 82 nef alleles cloned from brain, cerebral spinal fluid, spinal cord, and blood/lymphoid tissue-derived HIV-1 isolates from seven subjects with HAD. CNS isolate-derived nef alleles were genetically compartmentalized and had reduced sequence diversity compared to those from lymphoid tissue isolates. Defective nef alleles predominated in a brain-derived isolate from one of the seven subjects (MACS2-br). The ability of Nef to down-modulate CD4 and MHC class 1 (MHC-1) was generally conserved among nef alleles from both CNS and lymphoid tissues. However, the potency of CD4 and MHC-1 down-modulation was variable, which was associated with sequence alterations known to influence these Nef functions. These results suggest that CD4 and MHC-1 down-modulations are highly conserved functions among nef alleles from CNS- and lymphoid tissue-derived HIV-1 isolates that may contribute to viral replication and escape from immune surveillance in the CNS.


Abnormal meiosis in an intersectional allotriploid of Populus L. and segregation of ploidy levels in 2x × 3x progeny.
Triploid plants are usually highly aborted owing to unbalanced meiotic chromosome segregation, but limited viable gametes can participate in the transition to different ploidy levels. In this study, numerous meiotic abnormalities were found with high frequency in an intersectional allotriploid poplar (Populus alba × P. berolinensis 'Yinzhong'), including univalents, precocious chromosome migration, lagging chromosomes, chromosome bridges, micronuclei, and precocious cytokinesis, indicating high genetic imbalance in this allotriploid. Some micronuclei trigger mini-spindle formation in metaphase II and participate in cytokinesis to form polyads with microcytes. Unbalanced chromosome segregation and chromosome elimination resulted in the formation of microspores with aneuploid chromosome sets. Fusion of sister nuclei occurs in microsporocytes with precocious cytokinesis, which could form second meiotic division restitution (SDR)-type gametes. However, SDR-type gametes likely contain incomplete chromosome sets due to unbalanced segregation of homologous chromosomes during the first meiotic division in triploids. Misorientation of spindles during the second meiotic division, such as fused and tripolar spindles with low frequency, could result in the formation of first meiotic division restitution (FDR)-type unreduced gametes, which most likely contain three complete chromosome sets. Although 'Yinzhong' yields 88.7% stainable pollen grains with wide diameter variation from 23.9 to 61.3 μm, the pollen viability is poor (2.78% ± 0.38). A cross of 'Yinzhong' pollen with a diploid female clone produced progeny with extensive segregation of ploidy levels, including 29 diploids, 18 triploids, 4 tetraploids, and 48 aneuploids, suggesting the formation of viable aneuploidy and unreduced pollen in 'Yinzhong'. Individuals with different chromosome compositions are potential to analyze chromosomal function and to integrate the chromosomal dosage variation into breeding programs of Populus.


[Detection of P-glycoprotein and its clinical significance].
There is considerable variation in the assays used to evaluate the expression of mdr1 in various human malignancies. Current methodology includes reverse transcriptase polymerase chain reaction (RT-PCR) for assay of mdr1 mRNA, and immunohistochemistry or flow cytometry for detection of the multidrug transporter, P-glycoprotein(P-gp). Normal tissues, such as gastrointestinal mucosa, biliary tract and kidney, express high levels of P-gp, which suggests physiologic functions for this transporter. The some evidence suggests that mdr1 expression is a prognostic factor for response to chemotherapy, as well as for subsequent survival in various kind of tumors. We have developed a novel method using flow cytometry for detection of P-gp in gastric carcinomas. A strong correlation was noted between the flow cytometric data and the degree of drug resistance assessed by thymidine incorporation assay (TIA). We believe that this technique may have a significant potential to be utilized in prediction of P-gp related drug resistance in clinical cancer chemotherapy.


Tool use as situated cognition.
Vaesen disregards a plausible alternative to his position, and so fails to offer a compelling argument for unique cognitive mechanisms. We suggest an ecological alternative, according to which divergent relationships between organism and environment, not exotic neuroanatomy, are responsible for unique cognitive capacities. This approach is pertinent to claims about primate cognition; and on this basis, we argue that Vaesen's inference from unique skills to unique mechanisms is unwarranted.


Postoperative Radiotherapy and Facial Nerve Outcomes Following Nerve Repair: A Systematic Review.
To compare outcomes of facial nerve repair or grafting following facial nerve-sacrificing procedures among patients treated with and without postoperative radiotherapy (RT). PubMed, OVID, Conference Papers Index, Cochrane Library, ClinicalTrials.gov. Databases were searched using terms including "facial nerve," "graft," "repair," and "radiotherapy." Abstracts mentioning facial nerve repair and evaluation of facial nerve function were included for full-text review. Studies that utilized the House-Brackmann or similar validated scale for evaluation of postoperative facial nerve function were selected for review. All identified studies were included in a pooled t test analysis. Twelve studies with 142 patients were included in the systematic review. All 12 studies individually demonstrated no significant difference in facial nerve outcomes between patients who received postoperative radiation and patients who did not. A pooled t test of data from all studies also demonstrated no significant difference in postoperative facial nerve function between the postoperative RT and non-RT groups (t stat = 0.92, p = .36). This analysis, including 12 studies, demonstrated that among patients undergoing facial nerve grafting or repair, there was no significant difference in postoperative facial nerve function between postoperative RT and non-RT patients. Due to the small sample size and variability in study methods, further studies directly comparing outcomes between patients with and without postoperative RT would be beneficial.


Differences of resting fMRI and cognitive function between drug-naïve bipolar disorder and schizophrenia.
Bipolar disorder (BD) and schizophrenia (SC) have many similarities in clinical manifestations. The acute phase of BD has psychotic symptoms, while SC also has emotional symptoms during the onset, which suggests that there is some uncertainty in distinguishing BD and SC through clinical symptoms. To explore the characteristics of brain functional activities and cognitive impairment between BD and SC. Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) test was performed on patients in drug-naïve BD and SC (50 subjects in each group), and resting-state functional magnetic resonance imaging (rs-fMRI) scanning was performed meanwhile. Rs-fMRI data were routinely preprocessed, and the value of the fractional amplitude of low-frequency fluctuation (fALFF) was calculated. Then each part of the scores of the RBANS and the characteristics of brain function activities were compared between the two groups. Finally used Pearson correlation to analyze the correlation between cognition and brain function. (1) Compared with BD group, all parts of RBANS scores in SC group decreased; (2) The left inferior occipital gyrus (IOG, peak coordinates - 30, -87, -15; t = 4.78, voxel size = 31, Alphasim correction) and the right superior temporal gyrus (STG, peak coordinates 51, -12, 0; t = 5.08, voxel size = 17, AlphaSim correction) were the brain areas with significant difference in fALFF values between BD and SC. Compared with SC group, the fALFF values of the left IOG and the right STG in BD group were increased (p < 0.05); (3) Pearson correlation analysis showed that the visuospatial construction score was positively correlated with the fALFF values of the left IOG and the right STG (rleft IOG = 0.304, p = 0.003; rright STG = 0.340, p = 0.001); The delayed memory (figure recall) score was positively correlated with the fALFF value of the left IOG (rleft IOG = 0.207, p = 0.044). The cognitive impairment of SC was more serious than BD. The abnormal activities of the left IOG and the right STG may be the core brain region to distinguish BD and SC, and are closely related to cognitive impairment, which provide neuroimaging basis for clinical differential diagnosis and explore the pathological mechanism of cognitive impairment.


Endogenous clock gene expression in the suprachiasmatic nuclei of previsual newborn rabbits is entrained by nursing.
The rabbit is particularly suitable for investigating the development of mammalian circadian function. Blind at birth, the pups are only visited by the mother to be nursed once every 24 h for about 3 min and so can be studied largely without maternal interference. They anticipate the mother's visit with increased behavioral arousal and with a rise in body temperature, both of which represent endogenous circadian rhythms. We now report that in newborn pups the suprachiasmatic nuclei of the hypothalamus (SCN; the main circadian pacemaker in mammals) show endogenous 24-h rhythmicity in the expression of the clock genes Per1, Per2, and Bmal1. Pups nursed from postnatal days 1 to 7 and fasted to day 9 showed the same rhythms of clock gene expression as normally nursed controls. We also report that these rhythms are entrained by nursing. Pups killed on postnatal days 3-4 showed the same rhythms in gene expression as pups in the previous experiment, whereas littermates subsequently nursed from postnatal days 4 to 7 with nursing delayed 6 h showed a corresponding shift in the diurnal pattern of clock gene expression. Consistent with this, two groups of pups implanted with telemetric thermal sensors and nursed 6 h apart had daily patterns in body temperature synchronized with the two different nursing times. We conclude that the expression of clock genes associated with the newborn rabbit's circadian system is entrained by nonphotic cues accompanying nursing, the exact nature of which now needs to be clarified.


Choroidovitreal neovascular ingrowth after photocoagulation for proliferative diabetic retinopathy.
In eight patients with proliferative diabetic retinopathy treated with focal photocoagulation for preretinal new vessels, recurrent preretinal new-vessel systems supplied from the choroid developed. Subsequent treatment in most cases failed to produce permanent obliteration of the new-vessels networks.


Interleukin-1 induces a pertussis toxin-sensitive increase in diacylglycerol accumulation in mouse thymoma cells.
The mechanism of action of the cytokine, interleukin-1 (IL-1), has been investigated. Mouse thymoma (EL4 6.1) cells were preincubated with [3H]-glycerol and then incubated with recombinant IL-1 beta for varying periods. Interleukin-1 caused a rapid increase in diacylglycerol production (approx. 2 fold at 30 secs). This reproducible enhancement of diacylglycerol accumulation was abolished by pretreatment of the cells with pertussis toxin. Interestingly, a similar IL-1 induced increase in diacylglycerol was observed when the cells were preincubated with [3H]-myristic acid. These results appear to suggest a novel mode of action of interleukin-1 which involves a G-protein mediated breakdown of a membrane lipid resulting in the production of diacylglycerol. It is suggested that one possible candidate for this parent lipid may be a phosphatidylinositol glycan.


Polarization-switchable Q-switched DFB fiber laser.
A polarization switchable Q-switched distributed feedback (DFB) fiber laser is presented. This what we believe to be a new Q-switching method allows one to obtain linearly polarized laser emission in either x or y direction. The principle of this method is based on a variable birefringent phase shift induced by a lateral stress applied at a precise location along a fiber Bragg grating by a specially designed hyper-elastic device. A piezoelectric actuator controls the amount of stress delivered to the fiber, thus allowing a precise and rapid tuning of the cavity Q-factor.


Alterations of the anterior lens capsule in vitrectomized eyes with silicone oil tamponade.
To investigate the electron microscopic findings of the anterior lens capsule in vitrectomized eyes with silicone oil tamponade. Ten eyes of 10 consecutive patients aged 39 to 74 years who had cataract surgery combined with silicone oil removal from December 2006 to May 2009 were included in the study. The control group included 10 patients with cataract extraction and intraocular lens implantation without history of systemic or other ocular disease. All anterior capsules underwent electron microscopic examination of the anterior lens capsule. During the capsulorhexis, the anterior lens capsule was removed. In the silicone oil tamponade group, silicone oil droplets were detected on the posterior surface of the anterior lens capsule in 5 cases (50%) and surface irregularities, pits, and depressions were present in the posterior surface of the anterior lens capsules in all cases. Silicone oil droplets may infiltrate the lens capsule, especially in diabetic patients. Surface irregularities may be associated with posterior fibrous pseudometaplasia produced by lens epithelial cells under the anterior lens capsule.


Eating disorders and insulin-dependent diabetes mellitus (IDDM): relationships with glycaemic control and somatic complications.
This study was designed to assess (by means of a diagnostic interview based on DSM-III-R criteria) the prevalence of eating disorders in 69 insulin-dependent diabetic (IDDM) out-patients, and the relationship with somatic risks. We found no cases of anorexia nervosa or bulimia nervosa, current or lifetime, in male patients with IDDM. No female patients with IDDM had anorexia, and 4.8% had current and lifetime bulimia. Eating disorders not otherwise specified (bulimic type) were significantly more frequent in women than in men (lifetime incidence 43% vs. 21%; current incidence 33% vs. 5%), and generally occurred after the onset of IDDM. Self-reports of bulimic behaviours according to the Bulimic Investigatory Test of Edinburgh (BITE) were associated with high levels of glycosylated haemoglobin. There was no association between eating disorders (current or lifetime), with somatic complications being more likely to be explained by a long duration of illness and impaired glycaemic control.


[Preparation and characteristics of non-woven silk fibroin/nano-hydroxyapatite scaffolds].
The aim of the present study was to design and fabricate a three dimensional (3D) porous structure of silk fibroin/apatite used as a potential scaffold in bone tissue engineering. With the combining use of non-woven silk fibroin net and biomimetic method, porous non-woven silk fibroin/nano-hydroxyapatite net (NSF/nHAP) was prepared and characterized with X-ray diffraction (XRD), scanning electron microscope (SEM) and fourier transform infrared spectroscopy (FTIR). The porosity and swelling ratio of the 3D scaffold were also measured. Besides, the osteoblasts from the cranium of new born SD rat were cultured on the pre-fabricated scaffold to evaluate the biological reaction of the scaffold. The nano-sized hydroxyapatite crystals were needle-like with the length of 100-300 nm and the diameter of 20-60 nm. The scaffold fabricated in the present study exhibited the porous microstructure with open porosity around 70%-78%. Its average pore size was about (163.4 +/- 42.6) microm. The swelling ratio and water uptaking were 4.56% and 81.93%, respectively, which revealed that the 3D porous scaffold had an excellent hydrophilicity. The rod-shaped apatite crystals could rapidly form on the surface of fibroin fibers throughout the network by immersing the net into calcium and phosphate solutions alternatively. A 3D porous NSF/nHAP scaffold can be fabricated by biomimetic mineralization and none-woven silk fibroin method. The novel NSF/nHAP scaffold has an excellent cytocompatibility for the growth of osteoblasts. Porous NSF/nHAP scaffold may be a hopeful biomaterial used in bone tissue engineering.


Effect of ligation method on maxillary arch force/moment systems for a simulated lingual incisor malalignment.
The objectives of this study were to determine whether there is a difference in the magnitude of forces and moments produced by elastic ligation when compared to passive ligation, and whether these forces and moments propagate differently along the arch for the two ligation types. A lingual incisor malalignment was used in this study. The Orthodontic Simulator (OSIM) was used to quantify the three-dimensional forces and moments applied on the teeth given a lingually displaced incisor. A repeated measures MANOVA was performed to statistically analyze the data. The interaction factor illustrated convincing evidence that there is a difference in maximum force and moment values for all outcome variables between ligation types considering all tooth positions along the arch. The mean differences for FX and FY between ligation types were found to be clinically significant, with values for elastic ligation consistently higher than passive ligation. It was found that the maximum forces and moments produced by elastic ligation are greater than those produced by passive ligation and that the magnitude of this difference for the mesiodistal and buccolingual forces is clinically relevant. Additionally, it was determined that elastic ligation causes forces and moments to propagate further along the arch than passive ligation for all outcome variables.


Stabilization of Si(0) and Ge(0) compounds by different silylenes and germylenes: a density functional and molecular electrostatic study.
Recently, the chemistry of element (0) compounds has attracted the attention of both experimental and theoretical chemists. In this article, some new Si(0) and Ge(0) compounds stabilized by different silylene and germylene ligands are studied theoretically by applying quantum chemical calculations and topography mapping of molecular electrostatic potential (MESP). These compounds are found to have high donor-acceptor bond strengths and are thermodynamically stable. The nature of the molecular orbitals, negative values of MESP at its critical points, as well as proton affinity values suggest that they are very good nucleophiles. Calculated proton affinity values suggest the possible isolation of their diprotonated salts.


High resolution melting curve analysis enables rapid and reliable detection of G6PD variants in heterozygous females.
Like glucose-6-phosphate dehydrogenase (G6PD) deficient hemizygous males and homozygous females, heterozygous females could also manifest hemolytic crisis, neonatal hyperbilirubinemia or kernicterus upon exposure to oxidative stress induced by certain foods such as fava beans, drugs or infections. Although hemizygous males and homozygous females are easily detected by conventional G6PD enzyme assay method, the heterozygous state could be missed by the conventional methods as the mosaic population of both normal and deficient RBCs circulates in the blood. Thus the present study aimed to apply high resolution melting (HRM) curve analysis approach to see whether HRM could be used as a supplemental approach to increase the chance of detection of G6PD heterozygosity. Sixty-three clinically suspected females were evaluated for G6PD status using both enzyme assay and HRM analysis. Four out of sixty-three participants came out as G6PD deficient by the enzyme assay method, whereas HRM approach could identify nine participants with G6PD variants, one homozygous and eight heterozygous. Although only three out of eight heterozygous samples had G6PD enzyme deficiency, the HRM-based heterozygous G6PD variants detection for the rest of the samples with normal G6PD enzyme activities could have significance because their newborns might fall victim to serious consequences under certain oxidative stress. In addition to the G6PD enzyme assay, HRM curve analysis could be useful as a supplemental approach for detection of G6PD heterozygosity.


Critical incident interviewing in evaluation of resident performance.
To identify evaluation procedures for selection of radiology residents, this study was performed to describe the criteria that indicate successful resident performance. The critical incident technique, a method previously used in industrial settings, was applied. Structured interviews with 22 senior radiology staff members produced descriptions of resident behavior that fell into the following six categories: knowledge, technical skills and abilities, attitudes toward self, interpersonal skills, conscientiousness, and curiosity. The majority of behavioral factors appraised were in the last four categories, which describe personality variables and social skills. The results have implications for the evaluation and selection of residents.


[Particular aspects of bioelectric brain activity in post-traumatic Korsakoff syndrome].
Thirty two patients, 21 with recurrent and 11 with chronic Korsakoff's syndrome of traumatic genesis, and 20 healthy subjects were studied, using visual and spectral coherent EEG analysis and investigation of three-dimensional localization of dipolar beta 1-activity sources (13-20 Hz EEG bands). In Korsakoff's syndrome, negative prognostic significance of a stable increase of EEG beta 1-activity coherence generated by a limited number of sources, preferably of frontal basal and stem localization, was found. In the context of clinical data, this EEG phenomenon may be related to inhibited state of corresponding cortical areas.


A molecular dissection of the repression circuitry of Ikaros.
Ikaros is a key regulator of the hemo-lymphoid system in which it is presumed to function by both potentiating and repressing gene expression. Repression is mediated through two independent domains at the N and C terminus of the protein, both of which can independently recruit the corepressors Mi-2beta, Sin3A, and Sin3B and the Class I histone deacetylases 1 and 2; the N-terminal domain can also associate with the corepressor CtBP. Here we describe a detailed dissection of these two domains and identify the minimal repression modules and the corepressor requirements for their activity. Based on these studies, we describe mutations in a full-length Ikaros protein that abrogate interactions with each of the identified corepressors and abolish the protein's function as a repressor. Finally, we show that, barring CtBP, the Ikaros family members Aiolos, Helios, and Eos can associate with all of the identified corepressors of Ikaros including its newly identified interactors, Class II HDACs.


Neuropsychological, electroencephalogram and brain computed tomography findings in motor neuron disease.
Thirty-five patients affected with sporadic motor neuron disease (MND) and without clinically evident mental deterioration were systematically investigated by means of neuropsychological tests, quantitative analysis of EEG and brain CT. The MND patients as a group showed a slight but definite and stereotyped cognitive impairment. Temporal slow EEG activity was increased in the whole MND group and posterior background activity was slower in the more cognitively impaired patients. No significant differences were found in CT measurements of brain atrophy between MND and controls.


The Effect of Cognitive Activity on Sleep Maintenance in a Subsequent Daytime Nap.
Background/Objective: The aim of this study is to assess the effects of a learning task on the characteristics of a subsequent daytime nap. Participants and Methods: Thirty-eight subjects were administered a control nap (C) and one preceded by a cognitive training session (TR). Results: Relative to C, TR naps showed significantly increased sleep duration with decreased sleep latency, as well as significantly increased sleep efficiency due to reduced awakening frequency. Meaningful trends were also found toward an increase of Stage 2 sleep proportion and a reduction of Stage 1 sleep, percentage of wake after sleep onset (WASO), and frequency of state transitions. Conclusions: Our results indicate that presleep learning favors sleep propensity and maintenance, offering the possibility to explore planned cognitive training as a low-cost treatment for sleep impairments.


[Jewish socio-cultural aspects of Freud's thought].
Each original work, besides its scientific and universal characteristics, keeps links with the personality of its creator. Starting with evidence of the acceptance by Freud of his Jewish roots, we try to show that some aspects of psychoanalysis can be enlightened by considering specific problems of Judaism. The resemblance between psychoanalytical thinking and the Jewish mystical tradition is full of mystery.


Operative treatment of paediatric penetrating head injuries in southern Afghanistan.
The operative management and early post-operative outcome of 16 consecutive cases of paediatric penetrating head injury treated by a single surgeon at a military trauma centre in Southern Afghanistan are retrospectively analysed. The majority of cases of injury were caused by fragments from exploding munitions. The aim of neurosurgical intervention in penetrating head injury is the prevention of wound infection and treatment or prevention of a critical rise in intracranial pressure. In 14 cases in this study, these aims were fulfilled without resort to brain resection, although a delayed cranioplasty procedure was required in 6 patients. Despite the ongoing conflict, families, local communities and coalition forces transport teams combine to make the latter a viable option in Southern Afghanistan, with an excellent short-term outcome.


Capitalizing hidden values from hospital assets.
Benefits from selling noncore assets include generating capital and freeing up management resources. Monetization transaction structures include sale, partnership, and strategic affiliation. A hospital that engages in such a transaction needs to ensure that the purchaser or joint venture partner will maintain the hospital's high standards of care and ethical principles.


Palate re-repair revisited.
To analyze the results of a consecutive series of palate re-repairs performed using the operating microscope and identify predictive factors for outcome. Prospective data collection, with blind assessment of randomized recordings of speech and velar function on lateral videofluoroscopy and nasendoscopy. One hundred twenty-nine consecutive patients with previously repaired cleft palates and symptomatic velopharyngeal incompetence (VPI) and evidence of anterior insertion of the levator veli palatini underwent palate re-repairs by a single surgeon from 1992 to 1998. Syndromic patients, those who had significant additional surgical procedures at the time of re-repair (23 patients), and all patients with inadequate pre- or postoperative speech recordings were excluded, leaving a total of 85 patients in the study. Palate re-repairs, with radical dissection and retropositioning of the velar muscles, were performed using the operating microscope with intraoperative grading of anatomical and surgical findings. Pre- and postoperative perceptual speech assessments using the Cleft Audit Protocol for Speech (CAPS) score, measurement of velar function on lateral videofluoroscopy, and assessment of nasendoscopy recordings. There were significant improvements in hypernasality, nasal emission, and nasal turbulence and measures of velar function on lateral videofluoroscopy, with improvement in the closure ratio, velopharyngeal gap at closure, velar excursion, velar movement angle, and velar velocity. Palate re-repair has been shown to be effective in treating VPI following cleft palate repair, both in patients who have not had an intravelar veloplasty and those who have had a previous attempt at muscle dissection and retropositioning. Palate re-repair has a lower morbidity and is more physiological than a pharyngoplasty or pharyngeal flap.


Cloning and DNA sequence of the mercuric- and organomercurial-resistance determinants of plasmid pDU1358.
The broad-spectrum mercurial-resistance plasmid pDU1358 was analyzed by cloning the resistance determinants and preparing a physical and genetic map of a 45-kilobase (kb) region of the plasmid that contains two separate mercurial-resistance operons that mapped about 20 kb apart. One encoded narrow-spectrum mercurial resistance to Hg2+ and a few organomercurials; the other specified broad-spectrum resistance to phenylmercury and additional organomercurials. Each determinant governed mercurial transport functions. Southern DNA X DNA hybridization experiments using gene-specific probes from the plasmid R100 mer operon indicated close homology with the R100 determinant. The 2153 base pairs of the promoter-distal part of the broad-spectrum Hg2+-resistance operon of pDU1358 were sequenced. This region included the 3'-terminal part of the merA gene, merD, unidentified reading frame URF1, and a part of URF2 homologous to previously sequenced determinants of plasmid R100. Between the merA and merD genes, an open reading frame encoding a 212 amino acid polypeptide was identified as the merB gene that determines the enzyme organomercurial lyase that cleaves the C--Hg bond of phenylmercury.


A protocol for the use of computational fluid dynamics as a supportive tool for wastewater treatment plant modelling.
To date, computational fluid dynamics (CFD) models have been primarily used for evaluation of hydraulic problems at wastewater treatment plants (WWTPs). A potentially more powerful use, however, is to simulate integrated physical, chemical and/or biological processes involved in WWTP unit processes on a spatial scale and to use the gathered knowledge to accelerate improvement in plant models for everyday use, that is, design and optimized operation. Evolving improvements in computer speed and memory and improved software for implementing CFD, as well as for integrated processes, has allowed for broader usage of this tool for understanding, troubleshooting, and optimal design of WWTP unit processes. This paper proposes a protocol for an alternative use of CFD in process modelling, as a way to gain insight into complex systems leading to improved modelling approaches used in combination with the IWA activated sludge models and other kinetic models.


Effect of chemical treatment of poultry feed on survival of Salmonella.
After treatment with a chemical preservative [Myco Curb (Kemin Industries, Des Moines, IA) at .25, .5, .75, or 1.0%], sterilized commercial poultry feed was contaminated with either Salmonella typhimurium ATCC 6994 or with a strain isolated from commercial broiler carcasses. All treatments resulted in the elimination of detectable Salmonella from heavily contaminated feed within 72 h and from lightly contaminated feed within 24 h. Nonsterilized feed showed similar results. Commercial feed fed to broilers for 56 days and inoculated with Salmonella daily for Days 35 to 56 was treated with the chemical preservative at .5 and 1.0% for the last 7 days. Treatment resulted in a reduction of the number of fecal and intestinal samples positive for Salmonella, demonstrating elimination of Salmonella in the feed by use of the feed preservative.


Profiling and accurate quantification of Rubus ellagitannins and ellagic acid conjugates using direct UPLC-Q-TOF HDMS and HPLC-DAD analysis.
Accurate quantification and structural characterization of ellagitannins and ellagic acid conjugates in food, beverages, and food supplements are essential starting points for studying their effect on human health. However, accuracy is hindered both by the lack of pure standard compounds and by methods that maintain the compounds in their native form, avoiding any chemical modification of the structure. The objective of this work was to develop a new method for the purification, chromatographic separation, and accurate quantification of ellagitannins and ellagic acid conjugates to provide thorough characterization of the diversity in composition of 11 Rubus cultivars grown in Trentino, Italy. As such, two major steps were required: (i) the isolation and purification (with associated detailed structural characterization and determination of their molar extinction coefficients) of sanguiin H-6 and lambertianin C, providing essential data for their use, together with ellagic acid, as external standards, and (ii) the determination of the chemical structure of 20 novel minor ellagitannins and 4 ellagic acid conjugates on the basis of their Q-TOF-HDMS and DAD spectra. This survey of ellagitannins and ellagic acid conjugates provides evidence for the existence of significant differences in the pattern between and within blackberry and raspberry cultivars. To our knowledge, this is the first paper that has combined detailed metabolite profiling with accurate quantification of the main ellagitannins in Rubus using their respective standards.


CD8+ natural killer cells have a potential of a sensitive and reliable biodosimetric marker in vitro.
The aim of our work was to evaluate peripheral blood lymphocyte subsets as in vitro indicators of the received dose of ionizing radiation (biodosimetric markers) in the range of 3-20 Gy and to determine the appropriate time interval, during which a dose-dependent induction of apoptosis occurs upon gamma irradiation. In lymphocyte subsets characterized by double color surface immunophenotyping, four-color flow cytometry was used for visualizing cell death-associated increase in superficial phosphatidylserine exposure and cytoplasmic membrane permeability by fluorinated Annexin V and propidium iodide, respectively. No differences between sham-treated and lethal dose (7 Gy)-irradiated samples were observed upon 6 h cultivation in vitro. Ten and 18 h later, about 50 % of lymphocytes were apoptotic, but only the minority of them was in the late apoptotic phase. The only difference in radioresistance of the CD4(+)CD8(-) and CD4(-)CD8(+) lymphocyte subsets was seen upon 2-day cultivation when huge depletion of intact cells and prevalence of the late apoptotic population became obvious. A dose-dependence study in 16 and 48 h cultures confirmed the effectiveness of major T cell subsets as biodosimetric indicators. On the other hand, the minor CD8(+) subset of natural killer (NK) cells has been identified as a radiosensitive lymphocyte population the disappearance of which correlated with the received dose. We demonstrated that the CD3(-)CD8(+)NK subset can be used as a lethal/sublethal dose discriminator to 16 h cultivation. In addition, our data indicate that two-day cultivation followed by CD3/CD8 expression analysis in an intact lymphocyte population may provide a clue for low dosage biodosimetry.


Hemodynamic and cardiodynamic effects of propofol and etomidate: negative inotropic properties of propofol.
The hemodynamic effects of an induction dose of propofol, 2.5 mg/kg, or etomidate, 0.3 mg/kg, were studied in eight dogs. In addition, cardiodynamic changes were measured using a left ventricular catheter and needle force probes. Propofol was associated with significant decreases in systolic (19.9%) and diastolic (25.3%) arterial pressures associated with a 17.3% decrease in cardiac output (CO) and a 11.6% reduction in systemic vascular resistance (SVR) without change in pulmonary capillary wedge pressure (PCWP). These changes were most pronounced 1 min after the injection of propofol. At 5 and 10 min after the administration of propofol, heart rate (HR) decreased significantly. Minimal changes in hemodynamics were observed with etomidate. Propofol lowered systolic left ventricular pressure (LVPsys) by 17.6%. Signals generated by the force probes in the left ventricular myocardium showed a significant reduction (16.3%) in left ventricular force (LVF) and a decrease in early systolic rates of increase in force (dF/dt max) by 23.5% associated with propofol. In the presence of an unchanged preload, an unchanged HR, and a decreased SVR, the reduction in CO suggests that propofol has a negative inotropic effect. This negative inotropic effect was confirmed by a reduction in LVF and dF/dt max.


Spinal injury in car crashes: crash factors and the effects of occupant age.
Motor vehicle crashes are the leading cause of serious spinal injury in most developed nations. However, since these injuries are rare, systematic analyses of the crash factors that are predictive of spinal injury have rarely been performed. This study aimed to use a population-reference crash sample to identify crash factors associated with moderate to severe spinal injury, and how these vary with occupant age. The US National Automotive Sampling System Crashworthiness Data System (NASS) data for 1993-2007 were analysed using logistic regression to identify crash factors associated with Abbreviated Injury Scale (AIS)2+ spinal injury among restrained vehicle passengers. Risk of moderate or severe spinal injury (AIS2+) was associated with higher severity crashes (OR=3.5 (95% CI 2.6 to 4.6)), intrusion into an occupant's seating position (OR=2.7 (95% CI 1.9 to 3.7)), striking a fixed object rather than another car (OR=1.7 (95% CI 1.3 to 2.1)), and use of a shoulder-only belt (OR=2.7 (95% CI 1.5 to 4.8)). Older occupants (65 years or older) were at higher risk of spinal injury than younger adults in frontal, side and rollover crashes. Children under 16 were at a lower risk of spinal injury than adults in all crash types except frontal crashes. While the risk of serious spinal injury in motor vehicle crashes is low, these injuries are more common in crashes of higher severity or into fixed objects, and in the presence of intrusion. There are elevated risks of spinal injury for older occupants compared with younger adults, which may reflect changes in biomechanical tolerances with age. Children appear to be at lower risk of serious spinal injury than adults except in frontal crashes.


Polyphenols as potential preventers of osteoporosis: A comprehensive review on antioxidant and anti-inflammatory effects, molecular mechanisms, and signal pathways in bone metabolism.
Osteoporosis (OP) is a skeletal disorder characterized by decreased bone density, alterations in bone microstructure, and increased damage to the bones. As the population ages and life expectancy increases, OP has become a global epidemic, drawing attention from scientists and doctors. Because of polyphenols have favorable antioxidant and anti-allergy effects, which are regarded as potential methods to prevent angiocardipathy and OP. Polyphenols offer a promising approach to preventing and treating OP by affecting bone metabolism, reducing bone resolution, maintaining bone density, and lowering the differentiation level of osteoclasts (OC). There are multiple ways in which polyphenols affect bone metabolism. This article provides an overview of how polyphenols inhibit oxidative stress, exert antibacterial effects, and prevent the occurrence of OP. Furthermore, we will explore the regulatory mechanisms and signaling pathways implicated in this process.


Cellular Energetics as a Target for Tumor Cell Elimination.
Investigation of cancer cell metabolism has revealed variability of the metabolic profiles among different types of tumors. According to the most classical model of cancer bioenergetics, malignant cells primarily use glycolysis as the major metabolic pathway and produce large quantities of lactate with suppressed oxidative phosphorylation even in the presence of ample oxygen. This is referred to as aerobic glycolysis, or the Warburg effect. However, a growing number of recent studies provide evidence that not all cancer cells depend on glycolysis, and, moreover, oxidative phosphorylation is essential for tumorigenesis. Thus, it is necessary to consider distinctive patterns of cancer metabolism in each specific case. Chemoresistance of cancer cells is associated with decreased sensitivity to different types of antitumor agents. Stimulation of apoptosis is a major strategy for elimination of cancer cells, and therefore activation of mitochondrial functions with direct impact on mitochondria to destabilize them appears to be an important approach to the induction of cell death. Consequently, the design of combination therapies using acclaimed cytotoxic agents directed to induction of apoptosis and metabolic agents affecting cancer cell bioenergetics are prospective strategies for antineoplastic therapy.


Joint Intratracheal Surfactant-Antibacterial Therapy in Experimental Pseudomonas-Induced Pneumonia.
The application of an exogenous pulmonary surfactant as a carrier for intratracheally administered antimicrobials represents a promising therapeutic modality that is still on its way to clinical practice. Owing to its ability to decrease surface tension, exogenous surfactant may enhance delivery of antibiotics into foci of pulmonary infection, thus increasing efficiency and safety of topical antimicrobial therapy in bacterial lung diseases. To assess potential interactions between exogenous surfactant and amikacin in vitro, and to study the effects of their joint intratracheal instillation in rats with acute pneumonia caused by Pseudomonas aeruginosa. The antibacterial and surface-active properties of amikacin (Amicil, Kievmedpreparat, Ukraine), porcine pulmonary surfactant (Suzacrin, Docpharm, Ukraine), and their combination were studied in vitro using standard microbiologic procedures and modified Pattle method (estimation of bubble diameter). Similar methods were utilized to study bacterial contamination of lungs and blood, and to assess the surface activity of bronchoalveolar wash (BAW) in 119 Wistar rats, including infected (intratracheal introduction of P. aeruginosa ATCC 27853) and noninfected animals. Histopathologic findings, differential leukocyte counts, and oxygenation parameters were recorded. Antibacterial and surface-active properties of the surfactant and amikacin remained unimpaired in vitro. In rats anti-pseudomonal and anti-inflammatory effects of the surfactant-amikacin mixture were more pronounced (p<0.05) than effects of pure amikacin as evidenced by recorded rates of bacterial growth and granulocytic response. The combined therapy considerably restricted tissue damage and mitigated reduction of BAW surface activity. The advantages of the joint surfactant-amikacin therapy of Pseudomonas-induced pneumonia may suggest further clinical trials.


Development of a Multidimensional Attitude Scale for Organ Donation Research: An Example from China.
This research refined the notion of attitude based on the reasoned action perspective of organ donation research at both the conceptual and the operational levels in the Chinese context. In Study 1, a multidimensional attitude scale was developed based on the salient beliefs of the Chinese toward registering to become an organ donor, and the scale's reliability, convergent validity, and discriminant validity were established. The results of Study 1 indicated that the attitudes toward registering to become an organ donor consisted of two statistically independent dimensions, namely, positive and negative attitudes. In Study 2, the predictive validity of the multidimensional attitude scale was confirmed, and the results indicated that negative attitudes, positive attitudes, and subjective norms significantly impacted behavioral intention, which, in turn, predicted organ donor registration behavior.


Cerebral regulation of insulin secretion and the development of insulin resistance in type 2 diabetes.
Type 2 diabetes (T2DM) is a metabolic disorder that still constitutes a significant clinical problem due to its numerous micro- and macroangiopathic complications. Although many pathogenic factors for T2DM have been established to date, along with many methods of control and compensation, diabetes is still a subject of intense research aimed at finding new therapeutic regimens. Established protocols of management are based on the modification of risk factors and the administration of hypoglycemic agents, which act at the level of the pancreas or in target tissues for insulin. However, in recent years research has more and more frequently been centered upon the superior role of the central nervous system in the maintenance of the widely understood energy balance of the body, including carbohydrate metabolism. In this review the authors present current evidence confirming an association between the central nervous system (CNS) and insulin release, and discuss the potential risk of developing insulin resistance, obesity and diabetes in states of impaired CNS function. The key point of this review is to provide an analysis of a system of selected neuropeptides of central origin that act both at the level of the brain and in the periphery, playing an important role in the control of energy balance. The conclusions derived from the experimental studies and clinical trials discussed in this review undoubtedly suggest that impairment of the hereby presented system of central regulators can result in metabolic disorders.


Cloning and sequence analysis of putative glyceraldehyde-3-phosphate dehydrogenase gene from Monascus purpureus KCCM11832.
Using a synthetic oligonucleotide probe, glyceraldehyde-3-phosphate dehydrogenase gene (gpd1) was cloned from Monascus purpureus KCCM11832. The 2834 bp EcoRV-HindIII region harbored 1183 bp 5'-UTR containing such regulatory elements as CT box, common in fungal gpd's, and gpd box previously found exclusively in Aspergillus gpd's. Full-length cDNA was cloned by PCR, and its sequence was determined. Transcription starting point was located 88 bp upstream from start codon. Polyadenylation signal sequence occurred 201 bp downstream from stop codon. Region from start codon ATG to stop codon TAA including introns showed 62 approximately 69% nucleotide sequence identity to those of Aspergillus gpd's. Significant bias in third position, with pyrimidines favored over purines, was observed in codon usage. The deduced amino acid sequence had 81 approximately 85% identity to Aspergillus gpd's. Monascus purpureus GPD was located at the same clade with Aspergillus GPD's.


[Study of analgestic efficacy of ropivacaine-fentanyl patient-controlled epidural analgesia after upper abdominal gynecological surgery].
Most of the patients who undergo radical or subradical hysterectomy with paraaortic lymphadenectomy suffer from postoperative pain for upper abdominal incision. They also complain of postoperative nausea and vomiting (PONV) frequently, which are increased by opioids. Reducing total fentanyl dose to 0.6 mg, frequency of moving pain complaints increased gradually. Therefore, we introduced patient-controlled epidural analgesia (PCEA) for suppressing pain on moving. We investigated analgestic efficacy of 0.2% ropivacaine-fentanyl PCEA in twelve patients undergoing upper abdominal gynecological surgery. Postoperative analgesic effects were evaluated by visual analogue scale (VAS) at rest and on moving, times of bolus infusion, side effects, and degrees of satisfication by patient's self-assessments. Continuous epidural infusion of 0.6 mg fentanyl in 288 ml 0.2% ropivacaine was started at a rate of 4 ml x hr(-1) with a bolus dose of 2 ml. VAS was maintained below 20 mm at rest but was elevated to the maximum of 45 mm on moving with few bolus requests. Ninty-two percents of the patients answered satisfied but fifty percents of them had PONV. We conclude that ropivacaine-fentanyl PCEA is effective after upper abdominal gynecological surgery, and we can decrease the dose of fentanyl by explaining PCEA system more effectively to the patients for suppressing the pain on moving and PONV.


Management of the Cleft Nasal Tip: An Overview of Classic Techniques and Strategies.
The challenges of cleft reconstruction have been present for centuries. However, understanding of the cleft nasal tip and the evolution of techniques decidedly began in the 20th century and refinement continues into the present day. Although a multitude of technical descriptions and case series have been published, a compendium of seminal techniques, which have shaped modern thought, has not been compiled in the literature. In this review, we discuss the anatomical disturbances in the cleft nasal tip anomaly, the timing and strategy of tip correction, and the major classic techniques for management of the cleft nasal tip. In addition, we have categorized the classic techniques into concepts that they embody.


Antioxidant tolerance of kidney after irradiation.
Different doses of irradiation were performed in which group 1 (non-irradiated), group 2 (8 Gy/single dose/whole body) and group 3 (15 Gy/single dose/whole body) were formed of guinea pigs. After 24 hr of radiation exposure the levels of lipid peroxidation product, malondialdehyde, (MDA), glutathione (GSH) and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were measured in the whole kidney. The MDA content increased in animals irradiated with 8 and 15 Gy. And group 3 showed an increase the level of MDA. GSH contents of kidney in group 2 and 3 increased. The activity of SOD decreased markedly in group 3 when compared with control group. The activity of GSH-Px decreased significantly in group 2 and group 3 in comparison to controls. It may be concluded that a high dose of ionizing irradiation cause excessive oxidative stress in kidney.


Complete Genome Sequences of Nine Phages Capable of Infecting Paenibacillus larvae, the Causative Agent of American Foulbrood Disease in Honeybees.
We present here the complete genome sequences of nine phages that infect Paenibacillus larvae, the causative agent of American foulbrood disease in honeybees. The phages were isolated from soil, propolis, and infected bees from three U.S. states. This is the largest number of P. larvae phage genomes sequenced in a single publication to date.


Isolation, Identification and Antimicrobial Activity of Unprecedented Lactic Acid Bacterial Isolates from Honeybees.
Lactic acid bacteria are generally recognized as safe that could be beneficial for several uses in food industry to get their health benefits. The present study was focused on the isolation and identification of some new lactic acid bacteria that might be naturally occurred in the honeybees stomach and tried to explore their benefits. Twenty five isolates of lactic acid bacteria were isolated from the stomach of three different types of Egyptian bees (Apis mellifera lamarckii ), Carniolan bees (A.m. carnica) and hybrid Carniolan bees. Identification of isolates was carried out based on phenotypical tests and carbohydrate assimilation using API50 CHL and 16S rDNA sequencing. In the present study, the results emphasized Lactobacillus plantarum to be the predominant species (62.5%), other strains were identified as Pediococcus pentosaceus (12.5%), Lactobacillus pentosus (12.5%) and Lactobacillus sakei (12.5%). Eight of 25 isolates showed a potential antibacterial activity especially against Salmonella senftenberg strain. The novel isolates (HBMSS1, HBMSS3, HBMSS4, HBMSS5, HBMSS6 and HBMSS8) showed a significant antimicrobial activity against C. botulinum, E. coli, S. Senftenberg and S. epidermidis as food borne pathogens and P. larvae and M. plutonius as honeybee pathogens. These promising findings might be beneficial for discovering novel preservatives in food industry and substitution of antibiotic drugs used in the treatment of honeybees' infection.


Adhesion of resin-based sealers to dentine: an atomic force microscopy study.
To evaluate the effect of several final irrigants on the adhesion force (Fad) between dentine and resin-based sealers by means of atomic force microscopy (AFM). Twelve distal roots of mandibular molars were used. The roots were smoothened and cut to obtain 36 specimens. During chemomechanical preparation of the root canals, 5.25% NaOCl was used as the irrigant. The specimens were then divided into six groups according to the final irrigant used: control group - immersed in distilled water (DW) for 1 min; chlorhexidine (CHX) group - in 2% CHX for 1 min; NaOCl group - in 5.25% NaOCl for 1 min; EDTA group - in 17% EDTA for 5 min, EDTA/CHX group - in EDTA, followed by intermediate flushing with DW and then immersed in CHX; EDTA/NaOCl group - in EDTA, followed by intermediate flushing with DW and then immersed in NaOCl. After the treatments, all groups were washed with DW to remove all traces of the irrigants. Afterwards, the samples were dried and attached to a glass base. AFM tips containing AH Plus and Real Seal SE sealers were used to obtain force-distance curves with regard to dentine-treated surfaces. Data were analysed statistically using nonparametric tests with the significance level set at P < 0.05. In the groups with smear layer, a final flush with CHX and NaOCl resulted in significantly higher Fad values than the control group for both sealers (P < 0.001). When smear layer was removed, the highest Fad values associated with AH Plus occurred with a final flush of NaOCl, whilst in Real Seal SE, the highest values were found with a final flush of CHX (all results significant at P < 0.001). Irrigants had a positive effect on the adhesion of the resin-based sealers, AH Plus and Real Seal SE, to dentine.


P2X7 PET Radioligand 18F-PTTP for Differentiation of Lung Tumor from Inflammation.
Site-specific imaging agents play a key role in tumor targeting, but only a few agents are currently available for inflammation targeting. Since the P2X7 receptor (P2X7R) is a promising molecular target for inflammation, we evaluated the potential value of the 18F-labeled tracer 18F-PTTP (5-{[2-Chloro-3-(trifluoromethyl)phenyl]carbonyl}-1-pyrimidin-2-yl-4,5,6,7-tetrahydro-1H-[1,2,3]triazolo[4,5-c]pyridin) for targeting P2X7Rs and thus differentiating inflammation from tumors. Methods: The radioligand 18F-PTTP was achieved by a 1-step 18F-trifluoromethylation reaction. The binding affinity of the ligand for P2X7R and its stability were evaluated in vitro. Blood pharmacokinetics tests and biodistribution studies were performed in vivo. Dynamic 18F-PTTP small-animal PET/CT imaging was performed for 60 min on A549 tumor-bearing mice and inflammation-model mice for targeting differentiation. Results:18F-PTTP was afforded with decay-corrected radiochemical yields of 2.5%-7.0%, specific activity of 296-370 MBq/μmol, and radiochemical purity over 95%. 18F-PTTP showed excellent stability in 0.9% NaCl and 0.1% bovine serum albumin, good affinity to RAW264.7 cells, and rapid blood clearance in mice. In inflammation-model mice, uptake of 18F-PTTP peaked at 5 min after injection and kept at an imageable level till 30 min, whereas no significant radioactivity uptake was found in tumor grafts till 1 h after injection. The specificity of 18F-PTTP was verified by blocking studies and histologic analysis. Conclusion: The current study provides compelling data that 18F-PTTP is a novel radioligand targeting P2X7R and has potential to screen new drugs, quantify peripheral inflammation, and distinguish inflammation from certain solid tumors.


Vitreous Hyper-Reflective Dots in Optical Coherence Tomography and Retinal Tear in Patients with Acute Posterior Vitreous Detachment.
To report the presence of hyper-reflective dots in the vitreous cavity using spectral-domain optical coherence tomography (SD-OCT) in patients with acute symptomatic posterior vitreous detachment (PVD) and investigate their association with the presence of retinal tear. The medical records of 77 patients with acute symptomatic PVD, who were examined between March 2013 and February 2015, were reviewed. The severity of vitreous hyper-reflective dots (VHDs) was graded using SD-OCT images, and the presence of retinal tear was assessed. Forty-one (53.2%) eyes had mild VHDs, 13 (16.9%) eyes had moderate VHDs, and 14 (18.2%) eyes had severe VHDs. Retinal tear was found in 21 (27.3%) eyes. The presence of severe VHDs was associated with an increased likelihood of retinal tear (positive likelihood ratio, 9.78; 95% confidence interval, 3.02-31.63). In 14 (66.7%) eyes with retinal tear, the mean number of VHDs significantly decreased from 23.2 ± 20.27 to 2.3 ± 2.66 at a mean follow-up interval of 2.8 ± 1.48 weeks (P = 0.002). The presence of severe VHDs is suggestive of retinal tear in patients with acute symptomatic PVD. However, this SD-OCT finding should be limited to the acute phase of PVD.


Cerebral Venous Thrombosis and Persistent Pulsatile Tinnitus After Sigmoid Sinus Resurfacing Surgery.
We report a case with rare complication of cerebral venous thrombosis, as well as an incomplete response, after sigmoid sinus resurfacing surgery for pulsatile tinnitus (PT). A 24-year-old female patient with PT originating from the sigmoid sinus underwent sigmoid sinus resurfacing surgery. The tinnitus was immediately resolved, but it recurred with headache 5 days after surgery. A cerebral venous thrombosis was identified and treated, but PT persisted, although its frequency and loudness decreased. Sigmoid sinus resurfacing surgery is a safe and effective method to treat PT, but in some patients, it can cause serious complications and/or persistent tinnitus. In our patient, factors such as changes in blood viscosity due to warfarin intake or increased blood flow due to weight loss may have influenced the persistence of the tinnitus. It is important to identify the various associated factors and the weight of each of these factors to provide more tailored treatment of PT for individual patients in the future and to reduce complications and increase the effectiveness of sigmoid sinus resurfacing surgery.


Comparative efficacy and safety of Chinese herbal medicine for knee osteoarthritis: A protocol for systematic review and network meta-analysis.
Knee osteoarthritis (OA) is a major public health concern causing chronic disability as well as a substantial burden on health care and the economy. However, effective treatments for knee OA were still not available. Numerous clinical studies have suggested that Chinese herbal medicine (CHM) seems to be clinically effective in treating knee OA. Thus, this study aims to evaluate the efficacy and safety of CHM in the treatment of knee OA through a systematic review and network meta-analysis. A comprehensive search will be performed in PubMed, Cochrane Library, Embase, Web of Science, China National Knowledge Infrastructure, VIP Database, Wanfang Database, Chinese Biomedical Database, and 3 clinical trials registration websites, from the database inception to May 2021. Randomized controlled trials meeting the eligible criteria based on the PICOS framework will be included. All studies fulfilling the eligible criteria will be assessed for risk of bias using the Cochrane Collaboration's tool. The primary outcome will be the visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index, and total effective rate. The secondary outcome is the incidence of adverse events. Data analysis will be performed using Stata, Addis, and WinBUGS. This study will provide a reliable evidence to assess effectiveness and safety of CHM for knee OA, which may provide guidance for clinical practice. This study protocol has been registered on INPLASY202160060.


Pharmacokinetics of zileuton and its metabolites in patients with renal impairment.
The pharmacokinetics of zileuton and its conjugated metabolites were evaluated in patients with chronic renal impairment. Five healthy volunteers (creatinine clearance > 90 mL/min), five patients with renal failure requiring hemodialysis, six with mild (creatinine clearance, 60-90 mL/min), eight with moderate (creatinine clearance, 30-59 mL/min), and six with severe (creatinine clearance < 30 mL/min) renal impairment participated in the study. Zileuton was well tolerated by all participants including those with severe renal impairment and those receiving hemodialysis. The pharmacokinetics of zileuton were similar in healthy volunteers; in patients with mild, moderate and severe renal impairment; and in patients with renal failure requiring hemodialysis. The mean metabolite/parent-area ratios for the pharmacologically inactive zileuton glucuronides progressively increased with the decline in renal function. A very small percentage of the administered zileuton dose (< 0.5%) was removed by hemodialysis. Therefore, adjustment in the dose regimen of zileuton does not appear to be necessary for patients with various degrees of renal impairment and patients with renal failure requiring hemodialysis.


Possible mapping of the gene for transient myeloproliferative syndrome at 21q11.2.
The parental origin of the extra chromosome 21 was studied in 20 patients with trisomy 21-associated transient myeloproliferative syndrome (TMS) using chromosomal heteromorphisms as markers; this was combined with a study of DNA polymorphisms in 5 patients. Of these, 10 were shown to result from duplication of a parental chromosome 21, viz., maternal in 8 and paternal in 2. A patient with Down syndrome-associated TMS had a paracentric inversion in two of his three chromosomes 21 [47,XY,-21,+inv(21)(q11.2q22.13)mat,+inv(21)(q11.2 q22.13)mat]. These findings support our hypothesis of "disomic homozygosity" of a mutant gene on chromosome 21 in 21-trisomic cells as being a mechanism responsible for the occurrence of TMS. The finding also suggests that the putative TMS gene locus is at either 21q11.2 or 21q22.13, assuming that the gene is interrupted at either site because of the inversion. The study of 5 TMS patients using DNA polymorphic markers detected a cross-over site on the duplicated chromosomes 21 between 21q11.2 (or q21.2) and 21q21.3 in one patient, and a site between 21q21.3 and q22.3 in another patient, evidence that confined the gene locus to the 21cen-q21.3 segment. These findings suggest that the putative TMS gene is located at 21q11.2. The extra chromosome 21 in the latter two TMS patients probably resulted from maternal second meiotic non-disjunction, in view of the presence of recombinant heterozygous segments on their duplicated chromosomes 21.


Three pentacyclic triterpenes protect H9c2 cardiomyoblast cells against high-glucose-induced injury.
H9c2 cardiomyoblast cell line was used to examine the protection of three triterpenes, asiatic acid, boswellic acid, and oleanolic acid, at 5 or 10 μM against high-glucose-induced injury. High glucose stimulated reactive oxygen species (ROS), oxidized glutathione (GSSG), interleukin-6, tumor necrosis factor-alpha, and monocyte chemoattractant protein-1 production, as well as decreased glutathione peroxidase (GPX), glutathione reductase (GR) and catalase activities, and protein expression. However, pre-treatments of three triterpenes reserved glutathione, maintained activity and expression of GPX, GR, and catalase, as well as lowered ROS, GSSG, and inflammatory cytokines generation. High glucose reduced Na(+)-K(+)-ATPase activity, raised nuclear factor kappa (NF-κ) B and caspase-3 activities, up-regulated protein expression of NF-κB, mitogen-activated protein kinase, Bax, and cleaved caspase-3, as well as down-regulated Bcl-2 expression. Pre-treatments of three triterpenes retained Na(+)-K(+)-ATPase activity, declined NF-κB and caspase-3 activities, reserved Bcl-2 expression, as well as suppressed protein expression of NF-κB, p-p38, Bax, and cleaved caspase-3. These findings suggest that these triterpenes are potent cardiac-protective agents.


Endogenous inhibitor for calcium-dependent cysteine protease contains four internal repeats that could be responsible for its multiple reactive sites.
A cDNA encoding an endogenous inhibitor, termed calpastatin, for calcium-dependent cysteine protease (calpain, EC 220.127.116.11) was cloned by screening rabbit cDNA libraries with a synthetic oligodeoxynucleotide probe based on the partial amino acid sequence of the purified protein. The deduced amino acid sequence contains 718 amino acid residues (Mr, 76,964), and the mature protein corresponds to the deduced sequence from the 80th residue of the primary translation product (resultant Mr, 68,113). This deduced molecular weight is significantly lower than that determined by NaDodSO4/polyacrylamide gel electrophoresis, suggesting the possibility that the inhibitor is post-translationally modified. The sequence of the mature inhibitor contains four consecutive internal repeats approximately 140 amino acid residues long, each of which might be responsible for the inhibitory activity. Calpastatin is apparently different from a typical cysteine protease inhibitor (cystatin), suggesting that the mechanism of inhibition of calcium-dependent cysteine protease by the inhibitor might be different from that of other cysteine proteases by cystatin.


Intracellular expression of the T-cell factor-1 RNA aptamer as an intramer.
T-cell factor (TCF)-1 protein forms the transcriptional complex with beta-catenin and regulates the expression of diverse target genes during early development and carcinogenesis. We have selected previously an RNA aptamer that binds to the DNA-binding domain of TCF-1 and have shown that it interfered with binding of TCF-1 to its specific DNA recognition sequences in vitro. As an approach to modulate the transcription by TCF/beta-catenin complex in the cells, we have developed the RNA expression vector for stable expression of RNA aptamer inside of the mammalian cells. High level of RNA was expressed as an intramer in the fusion with the stable RNA transcript. The RNA intramer inhibited TCF/beta-catenin transcription activity as shown by luciferase assay. It also modulated the expression of TCF/beta-catenin target genes, such as cyclin D1 and matrix metalloproteinase-7, as predicted to be as an effective inhibitor of the TCF function. In addition, it efficiently reduced the growth rate and tumorigenic potential of HCT116 colon cancer cells. Such RNA intramer could lead to valuable gene therapeutics for TCF/beta-catenin-mediated carcinogenesis.


Virtual Interviews: A Cross-Sectional Quality Improvement Project Aimed to Improve the Interview Process in an Internal Medicine Residency Program.
The residency interview is a crucial step that helps the program identify potential new trainees while the trainees find out more about the program. With the onset of the COVID-19 pandemic, it became essential to hold interviews virtually. Here, we conducted a questionnaire-based study to identify areas of improvement in the virtual interview process in our program. The study was conducted among the residency interview applicants of the 2022 match cycle. A questionnaire was sent via email to all applicants who were invited to our residency program for an interview. Out of the 600 applicants who were interviewed in our program, 230 applicants answered the survey, an 11-point questionnaire pertaining to the various aspects of the interview process. A virtual interview with an option of in-person is the most favored answer among the different groups, i.e., American Medical Graduates (AMGs), International Medical Graduates (IMGs) without need for a visa, and IMGs with a need for a visa, respectively, were, 37.5%, 42.8%, and 38.65%, respectively. An updated website with all required information was a top resource used by 95%, 84.5%, and 89.6% of the different groups of candidates. American medical graduates (32.50%) place high importance on resident interaction, while international medical graduates want the programs to focus on their website and provide more information about all aspects of the program during the virtual interview. In the post-COVID-19 era, Internal Medicine programs will need to improve several aspects of virtual interviews while assessing what is important to candidates.


Slow light in an alternative row of ellipse-hole photonic crystal waveguide.
High normalized delay-bandwidth product (NDBP) and wideband slow light are achieved in an alternative row of ellipse-hole photonic crystal waveguide. Two different criteria of flat ratio are adopted. Under a constant group index criterion, a high NDBP of 0.446 with a group index of 42 and a bandwidth of 16.4 nm are obtained by plane wave expansion calculations, while under a low dispersion criterion, the NDBP, group index, and bandwidth come to 0.352, 41, 13.1 nm, respectively. Low dispersion slow light propagation is numerically demonstrated by studying the relative temporal pulse-width spreading with the two-dimensional finite-difference time-domain method. As a whole, the presented results give indications about the "ultimate" possible improvement of slow light waveguide metrics by using noncircular holes.


Percutaneous penetration of topically applied melatonin in a cream and an alcoholic solution.
In a clinical study, the skin penetration properties of melatonin 0.01% in a cream and 0.01 and 0.03% in a solution were investigated by evaluation of the serum melatonin levels over a 24-hour time course in 15 healthy volunteers. Blood samples for melatonin measurements were taken at 9.00 a.m. before applying the test preparations and 1, 4, 8 and 24 h after application. The measurements were carried out by radioimmunoassay for melatonin. In 15 volunteers, the serum levels of melatonin before application of the topical preparations were between 0.6 and 15.9 pg/ml. After application of the 0.01% melatonin cream, there was a steady increase starting from 9.00 a.m. up to a mean serum value of 9.0 pg/ml at 9.00 a.m. the next day. The solution of 0.01% melatonin also showed an increase, starting from 5.00 p.m., up to a mean melatonin level of 12.7 pg/ml 24 h after application. The solution containing 0.03% melatonin resulted in elevated melatonin levels 1 and 8 h after application. The values were 18.1 and 19.0 pg/ml. The cumulative melatonin values for each preparation were 7.1, 8.6 and 15.7 pg/ml, respectively. This study shows that the strongly lipophilic substance melatonin is able to penetrate through the skin and leads to dose- and galenic-dependent melatonin levels in the blood. No increase of melatonin above the physiological range was observed.


The role of routine serum testosterone testing: routine hormone analysis is not indicated as an initial screening test in the evaluation of erectile dysfunction.
A 60-year-old male physician is self-referred to your office for evaluation of his erectile dysfunction, which has been worsening for 5 years. He reports his erections rarely achieve fullness for penetration, and he is unable to ejaculate. He has tried sildenafil citrate (Viagra(R); Pfizer Inc, New York, NY) with mild success in the past. He has a strong libido and feels healthy. He rarely exercises, but is on his feet most of the day at work. He has been healthy his whole life and never seeks a doctor's attention. He has no other medical problems. His only medication is a baby aspirin once a day. His physical examination, including genitalia, is normal. As part of his initial visit, should his serum testosterone level be checked by his urologist?


A case of feline large granular lymphocyte lymphoma with complete remission and long survival by surgical resection and adjuvant nimustine administration.
A 7-year-old spayed female Scottish Fold cat presented with a 4-week history of anorexia, weight loss and vomiting. Abdominal ultrasonography revealed a jejunal mass and a slightly enlarged jejunal lymph node. A fine-needle aspiration of the mass revealed many round cells with multiple small intracytoplasmic magenta granules. The mass was diagnosed as a large granular lymphocyte (LGL) lymphoma based on cytology. The LGL lymphoma was completely resected via open surgery. The histologic and cytologic evaluations showed no neoplastic findings in the jejunal lymph node, liver, spleen, kidney or bone marrow. The LGL lymphoma was localized to the jejunum. Postoperatively, the cat received chemotherapy with nimustine, L-asparaginase and prednisolone. The cat is currently receiving nimustine every 6 weeks, without adverse events, and treatment has been administrated a total of 18 times up until day 552. The cat is in a good condition, and the LGL lymphoma has not recurred. Nimustine should be considered one of the effective chemotherapeutic agents in the treatment of feline LGL lymphoma cases in the future.