Short- and long-term monitoring of underwater sound levels in the Hudson River (New York, USA).
There is a growing body of research on natural and man-made sounds that create aquatic soundscapes. Less is known about the soundscapes of shallow waters, such as in harbors, rivers, and lakes. Knowledge of soundscapes is needed as a baseline against which to determine the changes in noise levels resulting from human activities. To provide baseline data for the Hudson River at the site of the Tappan Zee Bridge, 12 acoustic data loggers were deployed for a 24-h period at ranges of 0-3000 m from the bridge, and four of the data loggers were re-deployed for three months of continuous recording. Results demonstrate that this region of the river is relatively quiet compared to open ocean conditions and other large river systems. Moreover, the soundscape had temporal and spatial diversity. The temporal patterns of underwater noise from the bridge change with the cadence of human activity. Bridge noise (e.g., road traffic) was only detected within 300 m; farther from the bridge, boating activity increased sound levels during the day, and especially on the weekend. Results also suggest that recording near the river bottom produced lower pseudo-noise levels than previous studies that recorded in the river water column.


Do dogs eavesdrop on human interactions in a helping situation?
Eavesdropping is the acquisition of information by observing third-party interactions. Considering dogs' (Canis lupus familiaris) dependence on humans, it would be beneficial for them to eavesdrop on human interactions to choose an appropriate partner to associate with. Previous studies have found that dogs preferred a human who acted generously or cooperatively towards another human over one who acted selfishly or non-cooperatively, however they often did not control for potential location biases. This study controlled for local enhancement and investigated whether dogs derive and act on information about unfamiliar humans through reputation-like inferences by observing third-party interactions. 42 dogs participated in the experiment, which consisted of an observation phase and a test phase. In the observation phase, the animals observed a human with a box of food ask for help to open it from two people-one was helpful and the other was not. The test phase consisted of the impossible task and a choice test. Half of the sample was tested in the experimental condition and the other half was tested in the side control condition, where the two people swapped positions before the test phase. The results of the impossible task showed that dogs only looked at the helpful person first when the people stayed on the same side as they did in the observation phase. In the choice test, dogs chose at random, regardless of whether the people stayed on the same side or swapped positions. Our findings provide tentative support for a local enhancement interpretation of eavesdropping.


Base excision repair AP endonucleases and mismatch repair act together to induce checkpoint-mediated autophagy.
Cellular responses to DNA damage involve distinct DNA repair pathways, such as mismatch repair (MMR) and base excision repair (BER). Using Caenorhabditis elegans as a model system, we present genetic and molecular evidence of a mechanistic link between processing of DNA damage and activation of autophagy. Here we show that the BER AP endonucleases APN-1 and EXO-3 function in the same pathway as MMR, to elicit DNA-directed toxicity in response to 5-fluorouracil, a mainstay of systemic adjuvant treatment of solid cancers. Immunohistochemical analyses suggest that EXO-3 generates the DNA nicks required for MMR activation. Processing of DNA damage via this pathway, in which both BER and MMR enzymes are required, leads to induction of autophagy in C. elegans and human cells. Hence, our data show that MMR- and AP endonuclease-dependent processing of 5-fluorouracil-induced DNA damage leads to checkpoint activation and induction of autophagy, whose hyperactivation contributes to cell death.


[Reliability and validity of a sub-health symptom check scale for college students].
To analyze the reliability and validity of a sub-health symptom check scale for college students. Using a multi-phase cluster sampling method, a total of 1200 college students from Changsha city were tested with a sub-health symptom check scale; 1143 valid questionnaires were received to assess the internal consistency reliability coefficient and split-half reliability coefficient; 111 students were retested 14 days later to assess the reliability of the scale, 112 students were also tested with the Symptom Checklist 90 (SCL-90) to evaluate the criterion-related validity of the scale. The Cronbach's alpha coefficient of the questionnaire was 0.946 and the test-retest correlation coefficient was 0.701. Taking SCL-90 as a criterion, the criterion-related validity of the scale was 0.875. The scores of the scale were significantly different in gender and between sub-healthy and healthy students. The scale is reliable, effective, and sensitive, and could be applied to evaluate the sub-health status of college students.


Physical performance and short-term mortality in very old Mexican Americans.
BACKGROUND/STUDY CONTEXT: Physical performance measures have been found to be strong predictors of adverse outcomes in aging populations. Few studies have examined the predictive ability of physical performance measures exclusively within populations of the very old. This study explores the predictive ability of the Short Physical Performance Battery (SPPB) and its three subcomponents-a timed walk, balance test, and repeated timed chair stands-on mortality in a sample of Mexican Americans aged 75 and older. Logistic regression analyses were used with data from the Hispanic Established Population for the Epidemiological Study of the Elderly (Hispanic EPESE), to investigate the relationship between timed walk, balance test, repeated timed chair stands, and the SPPB and mortality over a 2½-year period. The authors find that being unable to complete the timed walk, the balance test, and repeated timed chair stands, or unable to complete any of the SPPB was significantly associated with mortality over 2½ years. These findings indicate that physical performance measures may be less predictive of short-term mortality in very old Mexican Americans than previously thought. More research is needed to understand this relationship.


Effect of acetylcholine deficiency on neural oscillation in a brainstem-thalamus-cortex neurocomputational model related with Alzheimer's disease.
Previous works imply that involving brainstem in neuropathological studies of Alzheimer's disease (AD) is of clinically significant. This work constructs a comprehensive neural mass model for cholinergic neuropathogenesis that involves brainstem, thalamus and cortex, wherein how acetylcholine deficiency in AD affects neural oscillation of the model output is systematically explored from the perspective of neurocomputation. By decreasing synapse connectivity parameters in direct cholinergic pathway from brainstem to thalamus or in indirect glutamatergic synapse pathway from cortex to brainstem to mimic the pathological condition of reduced acetylcholine release in patients with AD, the property of neural oscillation in this model is numerically investigated by means of power spectrum in frequency domain and amplitude distribution in time domain. Simulated results demonstrate that decreasing synapse connectivity whether in the direct cholinergic pathway or in the indirect glutamatergic synapse pathway can alter the neural oscillation significantly in three aspects: it induces an obvious decrease of dominant frequency; it leads to a degraded rhythmic activity in the alpha frequency band as well as an enhanced rhythmic activity in the theta frequency band; it results in reduced oscillation amplitude of the model output. These results are agreement with the characteristic of electrophysiological EEG measurement recorded in AD, especially support the hypothesis that cholinergic deficiency is a promising pathophysiological origin of EEG slowing in AD. Our analysis indicates that targeting the cholinergic system may have potential prospects in early diagnosis and treatment of AD.


Fatal air embolism: A grave complication during diagnostic flexible bronchoscopy.
Flexible fiber-optic bronchoscopy is used to determine diagnoses in pulmonary diseases. It is considered as a safe procedure, although some complications might occur, one of which is cerebral air embolism. In this case, we present the air embolism after the bronchoscopy procedure, ending in fatality. We strongly recommend that bronchoscopists should keep this complication in mind and be aware of early symptoms pertaining to the patient's state of consciousness during bronchoscopy examination. Early treatment is essential in this situation.


What Makes Telomeres Unique?
Telomeres are repetitive nucleotide sequences, which are essential for protecting the termini of chromosomes. Thousands of such repetitions are necessary to maintain the stability of the whole chromosome. Several similar repeated telomeric sequences have been found in different species, but why has nature chosen them? What features do telomeres have in common? In this article, we study the physical properties of human-like (TTAGGG), plant (TTTAGG), insect (TTAGG), and Candida guilermondi (GGTGTAC) telomeres in comparison with seven control, nontelomeric sequences. We used steered molecular dynamics with the nucleic acid united residue (NARES) coarse-grained force field, which we compared with the all-atom AMBER14 force field and experimental data. Our results reveal important features in all of the telomeric sequences, including their exceptionally high mechanical resistance and stability to untangling and stretching, compared to those of nontelomeric sequences. We find that the additional stability of the telomeres comes from their ability to form triplex structures and wrap around loose chains of linear DNA by regrabbing the chain. We find that, with slower pulling speed, regrabbing and triplex formation is more frequent. We also found that some of the sequences can form triplexes experimentally, such as TTTTTCCCC, and can mimic telomeric properties.


Transcriptome kinetics of arsenic-induced adaptive response in zebrafish liver.
Arsenic is a prominent environmental toxicant and carcinogen; however, its molecular mechanism of toxicity and carcinogenicity remains poorly understood. In this study, we performed microarray-based expression profiling on liver of zebrafish exposed to 15 parts/million (ppm) arsenic [As(V)] for 8-96 h to identify global transcriptional changes and biological networks involved in arsenic-induced adaptive responses in vivo. We found that there was an increase of transcriptional activity associated with metabolism, especially for biosyntheses, membrane transporter activities, cytoplasm, and endoplasmic reticulum in the 96 h of arsenic treatment, while transcriptional programs for proteins in catabolism, energy derivation, and stress response remained active throughout the arsenic treatment. Many differentially expressed genes encoding proteins involved in heat shock proteins, DNA damage/repair, antioxidant activity, hypoxia induction, iron homeostasis, arsenic metabolism, and ubiquitin-dependent protein degradation were identified, suggesting strongly that DNA and protein damage as a result of arsenic metabolism and oxidative stress caused major cellular injury. These findings were comparable with those reported in mammalian systems, suggesting that the zebrafish liver coupled with the available microarray technology present an excellent in vivo toxicogenomic model for investigating arsenic toxicity. We proposed an in vivo, acute arsenic-induced adaptive response model of the zebrafish liver illustrating the relevance of many transcriptional activities that provide both global and specific information of a coordinated adaptive response to arsenic in the liver.


Sorting nexin (MoVps17) is required for fungal development and plant infection by regulating endosome dynamics in the rice blast fungus.
Vps17 is a sorting nexin (SNX) and a component of the retromer, a protein complex mediating retrograde vesicle transport between endosomes and the trans-Golgi network. However, its role in the development and pathogenicity of filamentous fungi such as the rice blast fungus (Magnaporthe oryzae) remains unclear. We investigate the functional relationship between the SNX and the cargo-selective complex (CSC) of the fungal retromer by genetic analysis, live cell imaging and immunological assay. Our data show that the MoVps17 null mutation causes defects in growth, development and pathogenicity in M. oryzae. MoVps17 is localized to endosomes depending on the activity of phosphatidylinositol 3-kinase (PI3K), a key enzyme for fungal development and infection. Both PX and BAR domains of MoVps17 are essential for its endosomal localization and function. Furthermore, our yeast two-hybrid assays show that MoVps17 and MoVps5 can interact. Lastly, live cell imaging suggests that MoVps17 can regulate early endosome fusion and budding as well as endocytosis. Taken together, our results suggest that MoVps17 specifically functions as a retromer component with CSC and also plays a distinct role in the regulation of endosome dynamics during fungal development and plant infection.


Influence of thermal tempering processes on color characteristics of different monolithic computer-assisted design and computer-assisted manufacturing ceramic materials.
The optical properties of dental restoration were influenced by the sintering parameters. This study investigated the effects of different tempering processes on optical properties of three monolithic Cad-Cam ceramics. 135 monolithic material bars (4 mm width, 14 mm length, 1.2 mm thickness) were prepared from yttria-stabilized tetragonal zirconia polycrystalline (inCoris TZI, I), zirconia-reinforced lithium silicate (Vita Suprinity, V), and lithium disilicate glass (e.max CAD, E) ceramics, with different tempering processes through slow (S), normal (N), and fast (F) cooling (n=15). The color appearance (∆EW), translucency parameter (TP), contrast ratio (CR), and opalescence parameter (OP) were determined. ANOVA and Bonferroni's multiple comparisons were determined for significant difference (α=0.05). The grain sizes were microscopically examined by scanning electron microscope. The phase transformation of zirconia was determined using X ray diffraction. The mean±sd of ΔEW, TP, CR, OP were 74.15±0.46, 1.26±0.15, 0.977±0.006, 1.02±0.12 for IS; 74.00±0.83, 1.27±0.19, 0.977±0.007, 1.02±0.12 for IN; 74.44±0.64, 1.70±0.08, 0.965±0.003, 1.30±0.07 for IF; 73.35±1.32, 2.44±0.24, 0.958±0.006, 2.10±0.20 for VS; 66.37±0.88, 4.05±0.3, 0.911±0.010, 3.18±0.20 for VN; 67.02±0.65, 3.79±0.17, 0.919±0.006, 3.01±0.13 for VF; 60.01±0.30, 5.53±0.17, 0.821±0.006, 2.71±0.06 for ES; 60.18±0.23, 5.49±0.17, 0.822±0.006, 2.66±0.05 for EN; and 59.82±0.26, 5.36±0.06, 0.826±0.002, 2.64±0.07 for EF. The color parameters were significantly affected by type of materials, tempering processes, and their interactions (p<0.05). Phase transformation from t→m related with tempering procedure for zirconia. Rapid thermal tempering process of Y-TZP resulted in larger grain size and t→m phase transformation leading to higher translucency. To achieve optimum translucency, a fast thermal tempering process was suggested for inCoris TZI and IPS e.max CAD, whilst a normal tempering process was recommended for Vita Suprinity. Key words:Color, cooling process, contrast, opalescence, thermal tempering, translucency.


Bioactive Alkaloids from the Actinomycete Actinoalloteichus sp. ZZ1866.
The new alkaloids marinacarbolines E-Q (1-10, 12-14), caerulomycin N (15), and actinoallonaphthyridine A (16), together with the known marinacarboline C (11) and cyanogramide (17), were isolated from the actinomycete Actinoalloteichus sp. ZZ1866. The structures of the isolated compounds were elucidated based on their HRESIMS data, extensive NMR spectroscopic analyses, Mosher's method, ECD calculations, single-crystal X-ray diffraction analysis, and chemical degradation studies. Marinacarbolines E-L (1-8) share an indole-pyridone-imidazole tetracyclic skeleton, which is the first example of this kind of skeleton. Caerulomycin N (15) and cyanogramide (17) exhibited cytotoxic activity against both human glioma U251 and U87MG cells with IC50 values of 2.0-7.2 μM. Marinacarbolines E (1), G (3), I (5), and M (9) showed cytotoxic activity against U87MG cells with IC50 values of 2.3-8.9 μM.


Prevalence and correlates of fear of falling among elderly population in urban area of Karnataka, India.
Falls are a major public health problem in the elderly population. Fear of falling (FOF) among elderly persons can compromise quality of life by limiting mobility, diminished sense of well-being and reduced social interactions. India is undergoing a demographic transitional phase with urban elderly population of 6.72% in 2001. The major challenge would be on the prevention of falls among them. Hence there is a need to highlight the problems related to fall faced by the elderly in India. To study the prevalence of FOF and its correlates among the elderly population in urban area. 250 elderly subjects above 60 years were randomly selected from urban area and interviewed for FOF using Short Fall Efficacy Scale-I (FES-I), history of falls and risk factors. The prevalence of FOF among the elderly was 33.2%. The significant correlates of FOF were educational status, family type, associated health problems, history of fall in past 6 months, worried of fall again among fallers, fearfulness of fall again among fallers, restriction of daily activities and depression among them. The insignificant correlates were gender and socio-economic status. FOF is a health problem among the elderly living in urban India needs urgent attention. It represents a significant threat to socialization, independence and morbidity or mortality. Knowledge of correlates of FOF may be useful in developing multidimensional strategies to reduce it among elderly.


Is Rectosigmoid Vaginoplasty Still Useful?
The ideal vaginoplasty must be successful functionally as well as have a natural appearance, and also must retain its functionality and appearance over the long term. Conventional vaginoplasty techniques have functional limitations and are associated with recurrent complications, but rectosigmoid vaginoplasty is known to have a high satisfaction rate due to its functional similarity with the vagina. We conducted the present study to assess the usability of rectosigmoid vaginoplasty over the course of long-term follow-up. From March 1992 to February 2014, 84 patients were treated with rectosigmoid vaginoplasty; 44 had gender identity disorder, 29 had vaginal agenesis, 8 had female pseudohermaphroditism, and 3 had gynecologic malignancies after radical pelvic surgery. This retrospective study was based on a review of the patients' records, clinical examinations, complications, and questionnaires about appearance, function, and sexual intercourse. All patients who underwent rectosigmoid vaginoplasty were discharged within 2 weeks without surgical flap loss. The early complications were partial flap necrosis, difficulty in defecation, mucous hypersecretion, and postoperative ileus. The late complications were vaginal introitus contracture, vaginal prolapse, and difficulty in urination. The mean length and diameter of the neovagina 3.4 years after rectosigmoid vaginoplasty were 13.2 cm and 3.8 cm, respectively. On questionnaires about satisfaction, 70% of patients reported excellent satisfaction, 11% good, 12% fair, and 7% poor. Rectosigmoid vaginoplasty is useful, safe, and well-accepted operative method with good functional and cosmetic results, such as natural lubrication and adequate vaginal length and width obtained without requiring the use of a dilator.


Human leptospirosis in Erode, South India: serology, isolation, and characterization of the isolates by randomly amplified polymorphic DNA (RAPD) fingerprinting.
The study describes the first attempt to record leptospirosis in Erode by isolation and serological tests such as the microscopic agglutination test and IgM-based enzyme-linked immunosorbent assay. Twenty-nine clinically suspected cases showing fever, headache, body ache associated with jaundice, decreased urine output, and conjunctival suffusion were included. The age of the patients ranged between 10-71 years and most of them were agricultural workers. Paired sera were possible among 12 cases. All the patients had fever and headache and other more common symptoms were myalgia and icterus. Leptospiral culture was positive in 7 (24.1%) patients. Out of 29 patients, 26 (89.7%) were diagnosed as having current leptospiral infection based on serology and isolation. The leptospiral isolates KSR 1-6 were further characterized by using randomly amplified polymorphic DNA fingerprinting shown genetic similarities with Leptospira interrogans spp. This study shows the presence of leptospirosis among the hospital cases of Erode and that this disease is a potential health hazard of agricultural workers in Cauvery basin.


Retinal ganglion cell loss after the period of naturally occurring cell death in bcl-2-/- mice.
Over-expression of Bcl-2 is known to reduce the extent of retinal ganglion cell death during development as well as after axotomy. Here we investigated whether retinal ganglion cell (RGC) numbers are reduced in mice with a targeted inactivation of the bcl-2 gene. Compared with wild-type mice, adult bcl-2 null mutants have lost 29% of the retinal ganglion cell axons in the optic nerve. This reduction was almost fully established at P15, but not present at P10, which marks the end of the period of naturally occurring cell death. These observations, together with the previously reported late loss of primary motoneurons and peripheral neurons, point to a general physiological requirement for Bcl-2 soon after the period of naturally occurring cell death.


Anthropometric correlates to changes in visceral adipose tissue over 7 years in women.
To investigate the association between either increases or decreases in visceral adipose tissue and changes in anthropometric indices in a group of 32 women studied over a 7-y period. 32 women aged 35.1 +/- 5.4 (SD) years at baseline. Waist and hip circumferences, body fat mass (hydrostatic weighing) and viscera adipose tissue (computed tomography) were measured at baseline and at follow-up. Waist girth, waist-to-hip ratio, sagittal diameter and visceral adipose tissue area were all significantly higher at follow-up than at baseline (p < 0.05). Changes in visceral adipose tissue area were strongly correlated to changes in waist girth, hip girth, sagittal diameter and body fat mass (0.80 < or = r < or = 0.91 p < 0.0001). However, the association between changes in waist-to-hip ratio and those in visceral adipose tissue area was of low magnitude (r = 0.35; p = 0.05). Partial correlation analyses showed that the association between changes in visceral adipose tissue area and changes in either waist girth (p < 0.01) or sagittal diameter (p < 0.0001) remained significant even after control for 7-y variation in total body fatness. Results of the present study suggest that changes in visceral adipose tissue accumulation that occur with age in women are better predicted by changes in waist girth or sagittal diameter than by changes in waist-to-hip ratio.


Toll-like receptors 2 and 4 and the cryopyrin inflammasome in normal pregnancy and pre-eclampsia.
Pre-eclampsia involves a maternal inflammatory response that differs from both normal pregnancy and normotensive intrauterine growth restriction (IUGR). Our objective was to examine neutrophil Toll-like receptor (TLR), cryopyrin, nuclear factor-kappaB (NF-kappaB) subunit and interleukin-1beta (IL-1beta), and inflammatory cytokine profiles in women with pre-eclampsia or normotensive IUGR, as well as in normal pregnancy and non-pregnancy controls. A case-control study was performed. We examined the messenger RNA (mRNA) and protein expressions of TLR4 and TLR2, mRNA levels of cryopyrin, IL-1beta, NF-kappaB subunits p50 and p65, as well as maternal serum inflammatory cytokine profiles (IL-2, IL-6, tumour necrosis factor-alpha [TNF-alpha], interferon-gamma [IFN-gamma] and IL-10) in women with and without pre-eclampsia using real-time reverse transcription polymerase chain reactions, flow cytometry and multiplex immunoassays. A single tertiary maternity hospital in Vancouver, Canada. Women with early-onset pre-eclampsia (<34 weeks of gestation, n = 25), women with late-onset pre-eclampsia (>or=34(+0) weeks of gestation, n = 25), women with normotensive IUGR (n = 25), women with normal pregnancy (n = 75) and non-pregnancy (n = 25) controls. Women with pre-eclampsia (as a single combined group of early- and late-onset, and particularly in women with early-onset pre-eclampsia) had increased TLR2 and TLR4 mRNA and protein expressions elevated cryopyrin, NF-kappaB subunit, and IL-1beta mRNA expression, and TNF-alpha:IL-10 and IL-6:IL-10 ratios compared with other groups. These data suggest that TLRs and cryopyrin may modulate the innate immune response of the maternal syndrome of pre-eclampsia, and might also trigger the differential inflammatory response existing between early onset pre-eclampsia and normotensive IUGR.


Predifferentiated adult stem cells and matrices for cardiac cell therapy.
Stem cell therapy is a major field of research worldwide, with increasing clinical application, especially in cardiovascular pathology. However, the best stem cell source and type with optimal safety for functional engraftment remains unclear. An intermediate cardiac precommitted phenotype expressing some of the key proteins of a mature cardiomyocyte would permit better integration into the cardiac environment. The predifferentiated cells would receive signals from the environment, thus achieving gradual and complete differentiation. In cell transplantation, survival and engraftment within the environment of the ischemic myocardium represents a challenge for all types of cells, regardless of their state of differentiation. An alternative strategy is to embed cells in a 3-dimensional structure replicating the extracellular matrix, which is crucial for full tissue restoration and prevention of ventricular remodeling. The clinical translation of cell therapy requires avoidance of potentially harmful drugs and cytokines, and rapid off-the-shelf availability of cells. The combination of predifferentiated cells with a functionalized scaffold, locally releasing molecules tailored to promote in-situ completion of differentiation and improve homing, survival, and function, could be an exciting approach that might circumvent the potential undesired effects of growth factor administration and improve tissue restoration.


Synthesis, Structure, Surface and Antimicrobial Properties of New Oligomeric Quaternary Ammonium Salts with Aromatic Spacers.
New dimeric, trimeric and tetrameric quaternary ammonium salts were accomplished by reaction of tertiary alkyldimethyl amines with appropriate bromomethylbenzene derivatives. A series of new cationic surfactants contain different alkyl chain lengths (C4-C18), aromatic spacers and different numbers of quaternary nitrogen atoms. The structure of the products was confirmed by spectral analysis (FT-IR, ¹H-NMR, 13C-NMR and 2D-NMR), mass spectroscopy (ESI-MS), elemental analysis, as well as PM5 semiempirical methods. Compound (21) was also analyzed using X-ray crystallography. Critical micelle concentration (CMC) of 1,4-bis-[N-(1-alkyl)-N,N-dimethylammoniummethyl]benzene dibromides (3-9) was determined to characterize the aggregation behavior. The antimicrobial properties of novel QACs (Quaternary Ammonium Salts) were examined to set their minimal inhibitory concentration (MIC) values against fungi Aspergillus niger, Candida albicans, Penicillium chrysogenum and bacteria Staphylococcus aureus, Bacillus subtilis, Escherichia coli and Pseudomonas aeruginosa.


The impact of the bone marrow microenvironment on multiple myeloma (Review).
Multiple myeloma (MM) is characterized by the accumulation of monoclonal plasma cells in the bone marrow (BM). The interaction between the BM microenvironment and MM plasma cells can influence cell proliferation, drug resistance and prognosis of the disease. The BM microenvironment (BMME) consists of a cellular and non‑cellular compartment. The cellular compartment includes stromal cells, endothelial cells, osteoclasts and osteoblasts, and the non‑cellular compartment includes the extracellular matrix (ECM) and the liquid milieu, which contains cytokines, growth factors and chemokines. The complex interaction between the BM microenvironment and MM plasma cells influences disease development and prognosis. The present review focuses on the interaction between malignant plasma cells and the BM microenvironment during MM progression. An improved understanding of the interaction between MM plasma cells and their microenvironment will enable the development of novel therapeutic tools that can be used in the treatment of MM, a currently incurable blood cancer.


Mapping of an epitope of human leukocyte alpha interferon A which is recognized by the murine monoclonal antibody NK2.
An epitope of human leukocyte alpha interferon A (IFN-A), which is recognized by the murine monoclonal antibody NK2, has been mapped by using four successive approaches. Limited proteolysis of the IFN-A chain, followed by electrophoresis, Western blotting, and probing of the proteolytic fragments with NK2 showed that an epitope was located within the sequence residues 110-140. A panel of human IFN subtypes bearing substitutions within the sequence 110-140 was tested for reactivity with NK2 in enzyme-linked immunosorbent assays. The results from these assays suggested that the epitope is within the sequence 112-121. Analysis of a hybrid protein IFN-A(1-92)/F(93-166) revealed that the N-terminal region of IFN-A played no significant role in NK2 binding. Three residues of IFN-F (Asn113, Val114, and Lys121) were substituted for the corresponding residues from IFN-A (Lys113, Glu114, and Arg121) by site-directed mutagenesis of the gene encoding IFN-F. NK2 was able to bind the mutated protein, IFN-F(A 113, 114, 121), as well as unmodified IFN-A. The data show that the epitope recognized by NK2 is located within the C-terminal region of IFN-A (residues 112-121). This epitope consists of the essential residues 114 and 116, and residues 112, 113, 115, 117, and 121 presumably contribute the configuration of the epitope.


Reality check: Real-world evidence to support therapeutic development in hematologic malignancies.
The landscape for evidence generation in hematologic malignancies is rapidly evolving. While randomized controlled trials (RCTs) remain the gold standard in support of drug efficacy, approval and use, the supplemental use of real-world data (RWD), generated as part of routine healthcare delivery, and real-world evidence (RWE), the insights derived from RWD, in this setting has become increasingly common. There is a wide variety of sources of RWD, each with its own strengths and weaknesses that need to be considered when determining its appropriate use in RWE generation. RWD and RWE have historically been utilized in the post-approval setting to assess real-world application, efficacy, and safety of approved therapies. However, due to increasing awareness of the advantages of additional sources of information, RWE sourced from clinical data are being increasingly used to provide context for regulatory decision-making across several diseases including hematologic malignancies. Today, many commercial vendors offer fully aggregated, de-identified and standardized real-world clinical data. To maximize the potential of RWD and RWE, important considerations are needed to ensure patient privacy and to reduce the potential for biases and residual confounding. Continued collaboration among researchers, regulators and industry partners are needed to optimize evidence generation to ensure that new therapies reach patients as quickly and safely as possible.


[A case of Henoch-Schönlein purpura with relapse of ileitis and duodenitis for a short period].
A 60-year old man admitted our hospital due to abdominal pain, melena and arthralgia. There was purpura on his legs. On admission, the abdominal CT showed segmental mural thickening of terminal ileum and ascites. On the 4th hospital day, the abdominal CT showed severe mural thickening of the third portion of duodenum. On the 8th hospital day, the abdominal CT showed severe mural thickening of terminal ileum. We reported a rare case of Henoch-Schönlein purpura with relapse of ileitis and duodenitis for a short period which could be examined on the abdominal CT.


Left bundle branch block in infants with dilated cardiomyopathy conveys a poor prognosis.
We describe three infants <3 months of age seen consecutively with dilated cardiomyopathy who presented initially with left bundle branch block on the surface 12-lead electrocardiogram. Each infant subsequently had a poor outcome: two died and one required heart transplantation. These results suggest that the presence of left bundle branch block on the 12-lead electrocardiogram conveys a poor prognosis in infants with dilated cardiomyopathy.


Influence of AgCl precipitates on the precipitation titration of sodium chloride by constant-current coulometry.
The precipitation titration of sodium chloride with electrogenerated silver ion was studied. The production of a precipitate of silver chloride had a significant effect on the titration results because the precipitate involved unreacted chloride or unreacted silver ion. The accuracy of the method was investigated by changing the introduction time of a sodium chloride solution to the coulometric cell during the process of electrolysis, and examining the dependency on the sample size. The accuracy of the measurement of the precipitation titration is discussed.


"Masters and servants" in parkinsonian gait: a three-dimensional analysis of biomechanical changes sensitive to disease progression.
Gait disorder is a very frequent and disabling symptom in Parkinson's disease (PD). The aim of this study was to identify the main kinetic and kinematic features of PD gait according to different disease stages: early (Early Group), intermediate without freezing (Non-Freezers) and intermediate with freezing (Freezers). Kinematic data showed a distal to proximal progression of impairment from the early to the intermediate with freezing stage. The Early Group showed more accentuated ankle dorsiflexion during stance than the other PD subgroups; the Freezers showed a more flexed hip position at initial contact and a reduced range of motion (ROM) during stance compared with the other patients. The individuals in the intermediate stage (with or without freezing) displayed limited knee ROM. Distal to proximal progression of lower limb impairment in PD might be an expression of a rostral to caudal degeneration of locomotor control centers. Evaluation of the relationship between gait features "Masters and servants" in parkinsonian gait: a three-dimensional analysis of biomechanical changes sensitive to disease progression and disease progression may promote the development of tailored rehabilitation programs.


Triphenylamine-benzimidazole derivatives: synthesis, excited-state characterization, and DFT studies.
The synthesis and comprehensive characterization of the excited states of four novel triphenylamine-benzimidazole derivatives has been undertaken in solution (ethanol and methylcyclohexane) at room temperature. This includes the determination of the absorption, fluorescence, and triplet-triplet absorption spectra, together with quantum yields of fluorescence, internal conversion, intersystem crossing, and singlet oxygen. From the overall data the radiative and radiationless rate constants could be obtained, and it is shown that the compounds are highly emissive with the radiative decay dominating, with more than 70% of the quanta loss through this deactivation channel. The basic structure of the triphenylamine-benzimidazole derivatives (1a) was modified at position 5 of the heterocyclic moiety with electron-donating (OH (1b), OCH3 (1c)) or electron-withdrawing groups (CN, (1d)). It was found that the photophysical properties remain basically unchanged with the different substitutions, although a marked Stokes shift was observed with 1d. The presence and nature of a charge-transfer transition is discussed with the help of theoretical (DFT and TDFT) data. All compounds displayed exceptionally high thermal stability (between 399 and 454 °C) as seen by thermogravimetric analysis.


Loss of pRb2/p130 expression is associated with unfavorable clinical outcome in lung cancer.
Altered expression of cell cycle regulators represents a frequent event in both small cell and non-small cell lung cancer (NSCLC). Despite several studies that reported involvement of tumor suppressor genes, such as p53 and pRb, in the development and progression of lung cancer, contrasting opinions exist about the prognostic role of this protein in this neoplasm. We developed an immunohistochemical assay suitable for the detection of pRb2/p130, the last discovered member of the retinoblastoma gene family, on formalin-fixed and paraffin-embedded sections. We evaluated the immunohistochemical expression of pRb2/p130 in 135 lung cancer specimens, and performed Western blot analysis in a subset of 30 corresponding tumor lysates. A high correlation between immunohistochemical data and Western blot results (P = 0.0004) was found. We statistically analyzed the relationship between overall survival (OS) time and pRb2/p130 expression according to the different histological types in 105 patients. We did not find any correlation between pRb2/p130 expression and OS in small cell lung cancers, whereas in NSCLCs a direct relationship between pRb2 and OS was found in both adenocarcinoma (P = 0.0002) and squamous cell carcinoma (P = 0.0002) histotypes. According to univariate analysis, pRb2/p130 was a prognostic factor of which the lost or reduced expression correlated with a shorter OS (P < 0.0000). At multivariate analysis, pRb2/p130 expression was an independent predictor of OS (P = 0.0001) when considered together with histotype. This study demonstrates for the first time the potential independent prognostic value of pRb2/p130 expression on formalin-fixed, paraffin-embedded sections from lung cancer patients. pRb2/p130 immunoreactivity can be used to predict OS in patients with NSCLC and, therefore, may represent a new prognostic marker.


Opportunities and Challenges of Nanoparticles in Digestive Tumours as Anti-Angiogenic Therapies.
Digestive tumours, a common kind of malignancy worldwide, have recently led to the most tumour-related deaths. Angiogenesis, the process of forming novel blood vessels from pre-existing vessels, is involved in various physiological and pathological processes in the body. Many studies suggest that abnormal angiogenesis plays an important role in the growth, progression, and metastasis of digestive tumours. Therefore, anti-angiogenic therapy is considered a promising target for improving therapeutic efficacy. Traditional strategies such as bevacizumab and regorafenib can target and block the activity of proangiogenic factors to treat digestive tumours. However, due to resistance and some limitations, such as poor pharmacokinetics, their efficacy is not always satisfactory. In recent years, nanotechnology-based anti-angiogenic therapies have emerged as a new way to treat digestive tumours. Compared with commonly used drugs, nanoparticles show great potential in tumour targeted delivery, controlled drug release, prolonged cycle time, and increased drug bioavailability. Therefore, anti-angiogenic nanoparticles may be an effective complementary therapy to treat digestive tumours. In this review, we outline the different mechanisms of angiogenesis, the effects of nanoparticles on angiogenesis, and their biomedical applications in various kinds of digestive tumours. In addition, the opportunities and challenges are briefly discussed.


Treatment of angiolymphoid hyperplasia with eosinophilia with the carbon dioxide laser.
Angiolymphoid hyperplasia with eosinophilia (ALHE) is an uncommon, idiopathic condition that presents with isolated or grouped plaques or nodules in the periauricular region, forehead, or scalp. ALHE is marked by a proliferation of blood vessels with distinctive large endothelial cells accompanied by a characteristic inflammatory infiltrate that includes eosinophils. The lesion is benign but may be persistent and difficult to eradicate. Various therapeutic modalities that have been tried for its treatment include intralesional and oral corticosteroids, cryotherapy, oral retinoids, vinblastine, surgical excision, laser therapy, and INFalpha2a. We report two cases with this rare condition: one patient, treated with cryotherapy, did not improve, while the second patient was successfully treated with the CO(2) laser.


Combinational dual drug delivery system to enhance the care and treatment of gastric cancer patients.
Gastric cancer is a frequently occurring cancer with high mortality each year worldwide. Finding new and effective therapeutic strategy against human gastric cancer is still urgently required. Hence, we have established a new method to achieve treatment-actuated modifications in a tumor microenvironment by utilizing synergistic activity between two potential anticancer drugs. Dual drug delivery of gemcitabine (GEM) and Camptothecin-11 (CPT-11) exhibits a great anti-cancer potential, as GEM enhances the effect of CPT-11 treatment of human gastric cells by providing microenvironment stability. However, encapsulation of GEM and CPT-11 obsessed by poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) is incompetent owing to unsuitability between the binary free GEM and CPT-11 moieties and the polymeric system. Now, we display that CPT-11 can be prepared by hydrophobic covering of the drug centers with dioleoylphosphatidic acid (DOPA). The DOPA-covered CPT-11 can be co-encapsulated in PLGA NPs alongside GEM to stimulate excellent anticancer property. The occurrence of the CPT-11 suggestively enhanced the encapsulations of GEM into PLGA NPs (GEM-CPT-11 NPs). Formation of the nanocomposite (GEM-CPT-11 NPs) was confirmed by FTIR and X-ray spectroscopic techniques. Further, the morphology of GEM NPs, CPT-11 NPs, and GEM-CPT-11 NPs and NP size was examined by transmission electron microscopy (TEM), respectively. Furthermore, GEM-CPT-11 NPs induced significant apoptosis in human gastric NCI-N87 and SGC-791 cancer cells in vitro. The morphological observation and apoptosis were confirmed by the various biochemical assays (AO-EB, nuclear staining, and annexin V-FITC). In addition, evaluation of the hemolysis assay with erythrocytes of human shows excellent biocompatibility of free GEM, free CPT-11, GEM NPs, CPT-11 NPs, and GEM-CPT-11 NPs. The results suggest that GEM-CPT-11 NPs are one of the promising nursing cares for human gastric cancer therapeutic candidates worthy of further investigations.


Looking for the skeleton in the closet-rare genetic diagnoses in patients with diabetes and skeletal manifestations.
The precision medicine approach of tailoring treatment to the individual characteristics of each patient has been a great success in monogenic diabetes subtypes, highlighting the importance of accurate clinical and genetic diagnoses of the type of diabetes. We sought to describe three unique cases of childhood-onset diabetes in whom skeletal manifestations led to the revelation of a rare type of diabetes. METHODS : Case-scenarios and review of the literature. Case 1: A homozygous mutation in TRMT10A, a tRNA methyltransferase, was identified in a 15-year-old boy with new-onset diabetes, developmental delay, microcephaly, dysmorphism, short stature and central obesity. The progressive apoptosis of pancreatic beta cells required insulin replacement therapy, with increased demand due to an unfavorable body composition. Case 2: Congenital generalized lipodystrophy type 1 was suspected in an adolescent male with an acromegaloid facial appearance, muscular habitus, and diabetes who presented with a pathological fracture in a cystic bone lesion. A homozygous mutation in AGPAT2, an acyl transferase which mediates the formation of phospholipid precursors, was identified. Leptin replacement therapy initiation resulted in a remarkable improvement in clinical parameters. Case 3: A 12-year-old boy with progressive lower limb weakness and pain was diagnosed with diabetic ketoacidosis. Diffuse diaphyseal osteosclerosis compatible with the diagnosis of Camurati-Engelmann disease and a heterozygous mutation in TGFβ1 were identified. Preservation of euglycemia by insulin replacement relieved pain, suggesting that the diabetic milieu may have augmented TGFβ1 overexpression. Unraveling the precise genetic cause for the clinical manifestations led to the prediction of phenotypic manifestations, and enhanced the clinical outcomes.


Comparison of different approaches for calculation of polyelectrolyte free energy.
We consider the problem of the mean field (Poisson-Boltzmann) calculation of the electrostatic free energy for a strongly charged polyelectrolyte such as DNA in a salt solution. We compare two approaches to calculate the free energy: (i) direct one starting from the statistical-mechanical expression for the electrostatic free energy and (ii) the polyion charge variation method. In the infinite dilution limit (in respect to polyion) and in excess salt (IDLES) the two approaches are fully equivalent. This is shown by straight forward algebra. We have performed specific calculations of the free energy difference for the case of B-Z transition in DNA as a function of ionic strength. As expected, the two approaches led to identical results. The ionic strength dependence of the B-to-Z free energy proves to be concaved up and as a result Z-DNA is stabilized at low ionic concentration as well as at high salt, in full agreement with our previous results (M.D.Frank-Kamenetskii et al., J. Biomol. Struct. Dyn. 3, 35-42 (1985]. Our data quantitatively agree with the results of Soumpasis (D.M.Soumpasis, J. Biomol. Struct. Dyn. 6, 563-574 (1988]. However, his claim about the absence of the effect of stabilization of Z-DNA at low salt proves to be groundless, and the criticism of our earlier approach seems to be irrelevant.


Audio-Visual Temporal Recalibration Can be Constrained by Content Cues Regardless of Spatial Overlap.
It has now been well established that the point of subjective synchrony for audio and visual events can be shifted following exposure to asynchronous audio-visual presentations, an effect often referred to as temporal recalibration. Recently it was further demonstrated that it is possible to concurrently maintain two such recalibrated estimates of audio-visual temporal synchrony. However, it remains unclear precisely what defines a given audio-visual pair such that it is possible to maintain a temporal relationship distinct from other pairs. It has been suggested that spatial separation of the different audio-visual pairs is necessary to achieve multiple distinct audio-visual synchrony estimates. Here we investigated if this is necessarily true. Specifically, we examined whether it is possible to obtain two distinct temporal recalibrations for stimuli that differed only in featural content. Using both complex (audio visual speech; see Experiment 1) and simple stimuli (high and low pitch audio matched with either vertically or horizontally oriented Gabors; see Experiment 2) we found concurrent, and opposite, recalibrations despite there being no spatial difference in presentation location at any point throughout the experiment. This result supports the notion that the content of an audio-visual pair alone can be used to constrain distinct audio-visual synchrony estimates regardless of spatial overlap.


A Rare Case of Pulmonary Artery Sling with the VACTERL Association in a 20-Month-Old Infant.
The VACTERL association, co-occurrence of vertebral, anorectal, cardiac, tracheoesophageal, genitourinary, and limb malformations, is a rare congenital anomaly. Several cardiac anomalies have been reported as a part of the VACTERL association, particularly ventricular and atrial septal defects. Pulmonary artery sling is a rare congenital abnormality in which the left pulmonary artery arises from the right pulmonary artery. This anomaly is not frequently observed in the VACTERL association and has been rarely reported. A 20-month-old girl was admitted to our hospital due to pneumonia in the right lung, which had pulmonary artery sling as a part of the VACTERL association. Barium meal X-ray showed pressure effects on the esophagus, and computed tomography angiography revealed pulmonary artery sling. Pneumonia management was done. However, the parents of our patient refused to give consent for the surgical correction of this vascular anomaly. Three months after discharge from the hospital, the patient was visited, at which time the parents again refused surgery and treatment for their daughter despite our recommendations.


Therapeutic potency of curcumin for allergic diseases: A focus on immunomodulatory actions.
In light of increasing research evidence on the molecular mechanisms of allergic diseases, the crucial roles of innate and acquired immunity in the disease's pathogenesis have been well highlighted. In this respect, much attention has been paid to the modulation of unregulated and unabated inflammatory responses aiming to suppress pathologic immune responses in treating allergic diseases. One of the most important natural compounds with a high potency of immune modulation is curcumin, an active polyphenol compound derived from turmeric, Curcuma longa L. Curcumin's immunomodulatory action mainly arises from its interactions with an extensive collection of immune cells such as mast cells, eosinophils, epithelial cells, basophils, neutrophils, and lymphocytes. Up to now, there has been no detailed investigation of curcumin's immunomodulatory actions in allergic diseases. So, the present review study aims to prepare an overview of the immunomodulatory effects of curcumin on the pathologic innate immune responses and dysregulated functions of T helper (TH) subtypes, including TH1, TH2, TH17, and regulator T cells (Tregs) by gathering evidence from several studies of In-vitro and In-vivo. As the second aim of the present review, we also discuss some novel strategies to overcome the limitation of curcumin in clinical use. Finally, this review also assesses the therapeutic potential of curcumin regarding its immunomodulatory actions in allergic diseases.


Polycystic kidney disease: a 2011 update.
The review will examine clinically relevant advances in the area of polycystic kidney disease (PKD), mainly focusing on autosomal dominant polycystic kidney disease (ADPKD). Discussion will focus on predicting the course of ADPKD, clinical trials and new research endeavors. During the past several years PKD research has been one of the most prolific areas in investigative nephrology. Research endeavors have focused on decreasing cyst proliferation and cyst fluid formation based on an understanding of the pathophysiology of these processes. If cysts can be prevented from growing, kidney function can be better preserved. Progression of this most common inherited kidney disorder can be altered by understanding that cysts are the disease in ADPKD. Assessing total kidney volume and noting its relationship to glomerular filtration rate is key in predicting the course of the disease and will aid in the evaluation of the new research initiatives that are designed to stop cyst proliferation and fluid secretion into the kidney cysts. The role of biomarkers is an advancement in predicting PKD progression and can potentially be used in evaluation of treatments for this disease. Complications of PKD alter the course and prognosis; hence management approaches will be addressed.


Stamens and Gibberellic Acid in the Regulation of Flavonoid Gene Expression in the Corolla of Petunia hybrida.
Stamen removal at an early stage of flower development inhibits anthocyanin synthesis and chalcone flavanon isomerase (CHI) enzyme activity in corollas of Petunia hybrida. The inhibition can be overcome by gibberellic acid (GA(3)) application. Gibberellin also induces anthocyanin synthesis in detached, young green corollas, grown in vitro in a sucrose medium and promotes CHI enzyme activity. Western blot analysis indicates an increase in chalcone synthase (CHS) and CHI protein levels following GA(3) treatment in both the in vivo and the in vitro systems. Northern blot analysis shows a higher level of steady-state mRNAs for CHS and CHI 24 hours after GA(3) application. In corollas from a transgenic plant containing a beta-glucuronidase gene driven by a CHI promoter, a sixfold increase of beta-glucuronidase activity was measured following GA(3) application. The mode of action of stamens and GA(3) control over flavonoid gene expression is discussed.


Post-Brachytherapy Pigment Dispersion in Uveal Melanoma.
We report delayed intravitreal pigment dispersion following Iodine-125 plaque brachytherapy, without evidence of tumor recurrence, in 4 patients treated for choroidal melanoma. These patients were treated with Iodine-125 plaque brachytherapy, with or without transpupillary thermotherapy, and were followed clinically and using ancillary investigations for signs of tumor recurrence. All 4 patients were noted to develop pigment dispersion - it was detected on the surface of the retina (2 patients), diffusely in the vitreous (1 patient), or both (1 patient). Follow-up ranged from 70 to 343 months (mean 165 months; median 124 months) post-treatment with plaque brachytherapy, throughout which the location and amount of pigment remained grossly unchanged. None of the patients developed tumor recurrence or metastasis. We conclude that post-brachytherapy pigment dispersion is an unusual but known complication in the treatment of uveal melanoma. Close surveillance to rule out tumor recurrence and metastasis may be a reasonable line of management.


Valgus osteotomy of the proximal femur with sliding hip screw for the treatment of femoral neck nonunions: the technique, a case series, and literature review.
Femoral neck nonunions are a difficult complication in the treatment of femoral neck fractures and have traditionally been managed using an intertrochanteric valgus osteotomy and blade plate. We propose an alternative method, a proximal femoral valgus osteotomy using a sliding hip screw instead of a blade plate. This technique eliminates many of the difficulties experienced with the valgus osteotomy and blade plate by employing a device and instrumentation that is more familiar to orthopedic surgeons. The technique is reproducible and has been used successfully in a series of 4 patients.


[How patients react when glaucoma is diagnosed?].
Evaluate the psychological consequences of announcing the diagnosis of glaucoma. Two hundred patients completed a 20-item questionnaire designed to analyze the context in which glaucoma was discovered and the patients' reaction to this diagnosis. Behavioral modification in patients and their families are specified as well as their perception of the information received. Most patients had open-angle glaucoma and showed either an anxious or a passive reaction to the announcement of the diagnosis. Severe anxiety led to prescription of minor tranquilizers or antidepressants in 11% of cases. Nearly half of the patients declared that they had modified their behavior after receiving the diagnosis, indicating a need to play an active role in disease management. A large majority of the patients were conscious of the risk of blindness related to glaucoma; however, they did not feel ill but rather handicapped . Most were dissatisfied with the information provided by their doctor and sought other sources of information. Announcing a diagnosis of glaucoma is a decisive step in the physician-patient relationship, known to be important in future treatment compliance. Better adapted information with regular reevaluation of the need for additional information is necessary. The psychological impact should be evaluated regularly in order to promote an active role on the part of the patient and avoid a decline in quality of life.


Chile's dilemma: how to reinsert scientists trained abroad.
Chile is recognized worldwide as an emergent economy, with a great power in natural resource exploitation. Nonetheless, despite being one of the most developed countries in Latin America, Chile imports most of the knowledge and technology necessary to drive innovation in the country. The tight budget that the Chilean government assigned to research and development and the absence of a long-term scientific agenda contributed to a limited supply of scientists over the years. In an effort to reverse this scenario, Chile has created several fellowships, such as the Becas Chile Program (BCP) to encourage new generations to pursue graduate studies to ultimately advance research and development in situ. More than 6000 fellows are now being trained abroad, accumulating an incredible potential to transform the Chilean scientific environment as we know it. Chile now faces a greater challenge: it has to offer infrastructure and job openings to the highly skilled professionals in whom it invested. Unfortunately no clear public policies to address this situation have been developed, partially due to the lack of a dedicated institution, such as a Ministry for Science and Technology which could focalize the necessary efforts to promote such policies. Therefore, in the meantime, Chilean scientist have been motivated to create different organizations, such as, Mas Ciencia para Chile and Nexos Chile-USA, to promote constructive discussion of the policies that could be implemented to improve the Chilean scientific situation. We hope that these and other organizations have a real impact on the generation of scientific guidelines that will finally contribute to the development of the country.


Wet-chemistry processing of powdery raw material for high-tech ceramics.
The purpose of this study was to develop wet-chemistry approaches for the synthesis of ultradispersed and mesoporous metal oxide powders and powdery composites intended for usage in the production of ceramic materials with desired properties. The focus is on the development of template synthesis of mesoporous metal silicates as well as obtaining nano- and subnanopowders by a modified sol-gel technique and template methods. Families of mesoporous (2 to 300 nm) metal silicates and nano-oxides and subnanopowders (4 to 300 nm) were synthesized by the template method and modified sol-gel technique, respectively. Texture and morphology of the obtained objects have been studied by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, Fourier transform infrared spectroscopy, Brunauer-Emmett-Teller analysis, and N2 adsorption-desorption. It was found that morphological parameters of the metal oxide obtained by the modified sol-gel technique depend nonlinearly on the initial molar ratio value of the sol stabilizer and metal in the reaction medium as well as the nature of the stabilizer. It has been shown that the nature of structure-directing components determines the morphology of the silicate obtained by the template method: dispersion and shape of its particles. The developed laboratory technology corresponds to the conception of soft chemistry and may be adapted to the manufacture of ultradispersed materials for catalysis, solar cells, fuel cells, semiconductors, sensors, low-sized electronic devices of new generation, etc.


A Combined Morphologic and Molecular Approach to Retrospectively Identify KRAS-Mutated Mesonephric-like Adenocarcinomas of the Endometrium.
An unusual subset of endometrial carcinoma, the mesonephric-like adenocarcinomas, are morphologically and molecularly similar to mesonephric carcinoma, characterized by KRAS mutation and lack of microsatellite instability. They also have a unique immunohistochemical profile and are usually positive for GATA-3, CD10, TTF-1, and negative for ER and PR. This study implemented a combined morphologic and molecular approach to retrospectively identify mesonephric-like carcinomas of the endometrium. KRAS-mutated microsatellite stable (MSS) endometrial carcinomas were identified from a database of 570 endometrial carcinomas that had undergone massively parallel sequencing. MSS tumors with canonical KRAS mutations that lacked features diagnostic of endometrioid carcinoma (including squamous or mucinous differentiation), were re-reviewed for morphologic features of mesonephric-like adenocarcinomas. Ninty-eight of 570 endometrial carcinomas (17%) harbored canonical KRAS mutations. Of the KRAS-mutated cases, 80 (82%) were MSS and 18 (18%) had microsatellite instability. Of the KRAS-mutated MSS cases with morphology review, 39/61 (64%) had squamous and/or mucinous differentiation while 22 (36%) lacked these histotype-defining features. Eight of these 22 had PTEN mutations and lacked morphologic features of mesonephric-like adenocarcinoma, leaving 14 cases with a possible mesonephric-like adenocarcinoma-like molecular profile that underwent detailed morphologic re-review. Ten of 14 had morphology typical of serous (3), carcinosarcoma (4), or endometrioid (3) carcinoma. In 4 cases, there was striking morphologic, immunophenotypic, and molecular resemblance to mesonephric carcinoma, leading to re-classification as mesonephric-like adenocarcinoma. Two of the 4 cases presented at an advanced stage, and a third case later developed distant metastases. On the basis of this retrospective study, KRAS-mutated mesonephric-like adenocarcinoma represents ∼1% of all endometrial carcinomas. Future prospective recognition of this unusual variant of endometrial carcinoma may be important given its possible aggressive nature.


Roles of interleukin-12 and gamma interferon in murine Chlamydia pneumoniae infection.
BALB/c and strain 129 mice infected intranasally with Chlamydia pneumoniae displayed a moderate-to-severe inflammation in the lungs and produced interleukin-12 (IL-12), gamma interferon (IFN-gamma), tumor necrosis factor alpha (TNF-alpha), and IL-10, with peak levels on days 1 to 3 postinfection (p.i.), returning to basal levels by day 16 p.i. Anti-IL-12 treatment resulted in less-severe pathological changes but higher bacterial titers on days 3 and 7 p.i. By day 16 p.i., the inflammatory responses of control antibody-treated mice subsided. The bacterial titers of both anti-IL-12- and control antibody-treated mice decreased within 3 weeks to marginally detectable levels. Anti-IL-12 treatment significantly reduced lung IFN-gamma production and in vitro spleen cell IFN-gamma production in response to either C. pneumoniae or concanavalin A. In gamma-irradiated infected mice, cytokine production was delayed, and this delay correlated with high bacterial titers in the lungs. Following C. pneumoniae infection, 129 mice lacking the IFN-gamma receptor alpha chain gene (G129 mice) produced similar IL-12 levels and exhibited similarly severe pathological changes but had higher bacterial titers than 129 mice. However, by day 45 p.i., bacterial titers became undetectable in both wild-type 129 and G129 mice. Thus, during C. pneumoniae lung infection, IL-12, more than IFN-gamma, plays a role in pulmonary-cell infiltration. IFN-gamma and IL-12, acting mostly through its induction of IFN-gamma and Th1 responses, play an important role in controlling acute C. pneumoniae infection in the lungs, but eventually all mice control the infection to undetectable levels by IL-12- and IFN-gamma-independent mechanisms.


Mechanism and consequence of viral persistence in cells of the immune system and neurons.
Viral persistence depends on a virus having a non-lytic strategy of replication and the ability to escape immune surveillance. Cells of the immune system (lymphocytes/monocytes/macrophages) and central nervous system (neurons) are most often infected by DNA and RNA viruses that persist. Cytotoxic T lymphocytes (CTL) are the primary host defense that aborts or prevents viral persistence. Viral interaction with these specialized cells and of such infected cells with CTL is explored in this paper.


Interpretative criteria for the agar diffusion susceptibility test with azithromycin.
Azithromycin (CP-62,993) is a macrolide with a tendency to concentrate in various body tissues. Difficulties that arise when establishing tentative minimum inhibitory concentration (MIC) breakpoints for such a drug include the question of whether MICs should be compared with the achievable concentrations in blood or in tissue. Pending clinical experience with this drug, we recommend the following tentative criteria for interpreting tests with 15 micrograms azithromycin discs: susceptible greater than or equal to 18 mm (MIC less than or equal to 2 mg/l) and resistant less than or equal to 13 mm (MIC greater than or equal to 8 mg/l).


Halogenated veneers: protein cross-linking and halogenation in the jaws of nereis, a marine polychaete worm.
Mineralized tissues are produced by most living organisms for load and impact functions. In contrast, the jaws of the clam worm, Nereis, are hard without mineralization. However, they are peculiarly rich in halogens, which are associated with a variety of post-translationally modified amino acids, many of which are multiply halogenated by chlorine, bromine, and/or iodine. Several of these modified amino acids, namely dibromohistidine, bromoiodohistidine, chloroiodotyrosine, bromoiodotyrosine, chlorodityrosine, chlorotrityrosine, chlorobromotrityrosine, and bromoiodotrityrosine, have not been previously reported. We have found that the distributions of Cl, Br, and I differ: Cl is widespread whereas Br and I, although not colocalized, are concentrated in proximity to the external jaw surfaces. By using nanoindentation, we show that Br and I are unlikely to play a purely mechanical role, but that the local Zn and Cl concentrations and jaw microstructure are the prime determinants of local jaw hardness. Several of the post-translationally modified amino acids are akin to those found in various sclerotized structures of invertebrates, and we propose that they are part of a cross-linked protein casing.


Cast away in the Adriatic: Low degree of parallel genetic differentiation in three-spined sticklebacks.
The three-spined stickleback (Gasterosteus aculeatus) has repeatedly and independently adapted to freshwater habitats from standing genetic variation (SGV) following colonization from the sea. However, in the Mediterranean Sea G. aculeatus is believed to have gone extinct, and thus the spread of locally adapted alleles between different freshwater populations via the sea since then has been highly unlikely. This is expected to limit parallel evolution, that is the extent to which phylogenetically related alleles can be shared among independently colonized freshwater populations. Using whole genome and 2b-RAD sequencing data, we compared levels of genetic differentiation and genetic parallelism of 15 Adriatic stickleback populations to 19 Pacific, Atlantic and Caspian populations, where gene flow between freshwater populations across extant marine populations is still possible. Our findings support previous studies suggesting that Adriatic populations are highly differentiated (average FST ≈ 0.45), of low genetic diversity and connectivity, and likely to stem from multiple independent colonizations during the Pleistocene. Linkage disequilibrium network analyses in combination with linear mixed models nevertheless revealed several parallel marine-freshwater differentiated genomic regions, although still not to the extent observed elsewhere in the world. We hypothesize that current levels of genetic parallelism in the Adriatic lineages are a relic of freshwater adaptation from SGV prior to the extinction of marine sticklebacks in the Mediterranean that has persisted despite substantial genetic drift experienced by the Adriatic stickleback isolates.


Comparing PTSD treatment retention among survivors of military sexual trauma utilizing clinical video technology and in-person approaches.
Interventions such as Prolonged Exposure (PE) and Cognitive Processing Therapy (CPT) have demonstrated efficacy for the treatment of post-traumatic stress disorder (PTSD) following military sexual trauma (MST). However, MST survivors report a number of logistical and social barriers that impede treatment engagement. In an effort to address these barriers, the Veterans Health Administration offers remote delivery of services using clinical video technology (CVT). Evidence suggests PE and CPT can be delivered effectively via CVT. However, it is unclear whether rates of veteran retention in PTSD treatment for MST delivered remotely is comparable to in-person delivery in standard care. Data were drawn from veterans (N = 171, 18.1% CVT-enrolled) with PTSD following MST who were engaged in either PE or CPT delivered either via CVT or in person. Veterans chose their preferred treatment modality and delivery format in collaboration with providers. Data were analysed to evaluate full completion (FP) of the protocol and completion of a minimally adequate care (MAC) number of sessions. FP treatment completion rates did not differ significantly by treatment delivery format. When evaluating receipt of MAC care, CVT utilizers were significantly less likely to complete. Kaplan-Meier analyses of both survival periods detected significant differences in attrition speed, with the CVT group having higher per-session attrition earlier in treatment. Disengagement from CVT-delivered treatment generally coincided with early imaginal exposures and writing of trauma narratives. CVT providers may have to take special care to develop rapport and problem-solve anticipated barriers to completion to retain survivors in effective trauma-focused interventions.


Lessons learned from a longitudinal study of dementia care.
In a longitudinal study, the authors document the moves of dementia patients between different care settings, following up 103 individuals who had participated in an earlier study of the transition from home to institutional care. It was possible to document numerous moves between home, respite care, acute care hospital, and long-term care settings for these patients. The authors discuss the clinical implications of the many changes of residence for those suffering from dementia.


Utility of screening questionnaire, obesity, neck circumference, and sleep polysomnography to predict sleep-disordered breathing in children and adolescents.
Polysomnography (PSG) remains the gold standard for diagnosing obstructive sleep apnea (OSA) and sleep-disordered breathing in children. Yet, simple screening tools are needed as it is not feasible to perform PSG in all patients with possible OSA. The study adapted questions from the Pediatric Sleep Questionnaire-Sleep-Related Breathing Disorder (SRBD) Questionnaire to develop a predictive scale for OSA identified on PSG. We also tested whether adding anthropometric measurements (body mass index and neck circumference) improved prediction of OSA. After IRB approval, OSA questionnaires and anthropometric measurements were collected on 948 consecutive patients scheduled for PSG, aged 4 months to 24.5 years (median = 8.5 years). The sample was reduced to 636 patients in the age range (6-18 years old) where normative values for neck circumference are defined. OSA was characterized using the obstructive apnea-hypopnea index (AHI). After identifying questions related to OSA in univariate logistic regression, multivariable models were fitted to select questions for a short scale, and points for exceeding body mass or neck circumference cutoffs were added to assess improvement in predictive value. A long scale of 16 questionnaire items was constructed using univariate models, while six items were selected for the short scale by multivariable regression. The short scale was associated with greater odds of moderate/severe OSA (OR = 1.964; 95% CI = 1.620, 2.381; P < 0.001) and attained good predictive value (area under receiver operating characteristics curve [AUC] = 0.74), which was not significantly improved by addition of BMI and neck circumference data (AUC = 0.75). We developed a six-question scale with good predictive utility for OSA. These findings may contribute to developing a preoperative clinical tool to help clinicians identify children with OSA for determining risk stratification and postoperative disposition.


Two cases of aortoenteric fistula with gastrointestinal bleeding.
Aortoenteric fistula (AEF) is a life-threatening condition that can present with gastrointestinal (GI) bleeding. AEFs have been classified into primary and secondary types. Primary AEF (PAEF) is a direct communication between the aorta and the GI tract. Secondary AEF (SAEF) is the result of a previous abdominal aortic aneurysm repair involving placement of a synthetic aortic graft. Diagnosis of AEF, especially PAEF, is difficult largely because AEF is so rarely encountered in practice. Computed tomography (CT) and endoscopic gastroduodenoscopy (EGD) are most frequently used to diagnose AEF, with abdominal contrast-enhanced CT being the preferred initial diagnostic test of choice. Although EGD can exclude other common causes of GI hemorrhage, it cannot be used to rule out AEF when another source of bleeding is identified, as the two conditions can coexist. We discuss here two patients with GI bleeding who were diagnosed as PAEF and SAEF. We tried to diagnose and treat with EGD, but failed. That bleeding was due to an AEF became evident when abdominal CT scans revealed direct extravasation of contrast media from the abdominal aorta into the GI tract. The lack of awareness of AEF, coupled with the inaccessibility to the distal duodenum via EGD, were probably responsible for initial misdiagnosis and delay of appropriate management. We suggest that the diagnosis of AEF remains dependent on the clinician's heightened suspicion.


A new chemolithoautotrophic arsenite-oxidizing bacterium isolated from a gold mine: phylogenetic, physiological, and preliminary biochemical studies.
A previously unknown chemolithoautotrophic arsenite-oxidizing bacterium has been isolated from a gold mine in the Northern Territory of Australia. The organism, designated NT-26, was found to be a gram-negative motile rod with two subterminal flagella. In a minimal medium containing only arsenite as the electron donor (5 mM), oxygen as the electron acceptor, and carbon dioxide-bicarbonate as the carbon source, the doubling time for chemolithoautotrophic growth was 7.6 h. Arsenite oxidation was found to be catalyzed by a periplasmic arsenite oxidase (optimum pH, 5.5). Based upon 16S rDNA phylogenetic sequence analysis, NT-26 belongs to the Agrobacterium/Rhizobium branch of the alpha-Proteobacteria and may represent a new species. This recently discovered organism is the most rapidly growing chemolithoautotrophic arsenite oxidizer known.


Genetic factors in systemic sclerosis.
A number of genetic loci have been identified that appear to be associated with systemic sclerosis (SSc; scleroderma). There is mounting evidence suggesting that these genetic associations may in fact be associated with distinct phenotypes in SSc based on autoantibody pattern rather than with SSc as a single disease entity. This may ultimately have implications for approaches to therapy as well as responses to therapy. The most promising candidate genes are those involved in pathways that lead to the vascular damage and fibrosis that are the hallmarks of this disease. There is uncertainty, however, regarding the nature of the key pathological mechanisms that link these two disease processes. Recent studies have focused on Fli1 (friend leukaemia integration 1), a transcription factor that is found in immune cells, fibroblasts, and endothelial cells that regulates collagen gene function and angiogenesis. Fli1 is dysregulated in SSc skin and dermal blood vessels, and appears to play a pathological role in SSc skin fibrosis and vessel degeneration. Whether this dysregulation is due to genetic polymorphisms in the Fli1 pathway or to epigenetic mechanisms is not clear.


Using the D-DANP-mV Model to Explore the Continuous System Improvement Strategy for Sustainable Development of Creative Communities.
With globalization, the notion of "creative city" has become a core concept of many cities in the world development policies, with real properties being upgraded or used to change, renewal is being conducted, and creative industries are emerging. This trend has reached its peak in the past decade, with different forms and scales gathering global development momentum among the creative communities to promote the development of creative economies. In recent years, however, there was still skepticism about the sustainability of the current creative communities. Many scholars have pointed out that signs of unsustainability have begun to appear in many creative communities. To overcome these obstacles, the development of rational and highly effective improvement strategy requires a dynamic thinking process. Therefore, this study employs the DEMATEL-based ANP with modified VIKOR (D-DANP-mV) model in presenting an assessment framework for the sustainability of creative communities. This system is used to assess the sustainability of current creative communities and determine how to solve their problems. Thus, continuous and systemic improvement strategies can be developed to achieve the aim of sustainable development. Two creative communities in Taiwan, Taichung Cultural and Creative Industries Park (TCCIP), and Shen-Ji New Village (SJNV), are used as case studies in this study. Based on the concept of systematic improvement from fundamental issues, the results indicate that the improvement priorities can be determined by applying the D-DANP-mV model. This approach is different from those found by a conventional method with the hypothesis of independent criteria (e.g., diversification of creative talents in TCCIP), and cannot use for performance improvement (e.g., only can be used for ranking and selection among alternatives). Considering these points, unreasonable premises, biased errors, and lack of some real application functions in the process of resource allocation could be more efficient improvement strategies generated in this proposed model.


Effects of insulin on blood, plasma, and brain glucose in hyperglycemic diabetic rats.
This study, in biologically bred hyperglycemic diabetic rats, examined the effect of a intravenous insulin infusion (1.5 units.hr-1) on blood, plasma, and brain glucose concentrations to determine their relationship during decreasing blood and plasma glucose levels. The data were compared to saline-treated diabetic rats and saline-treated nondiabetic littermates. The volume and duration of the treatment infusion were similar in all groups. Insulin infusion in diabetic rats produced the expected reduction in blood and plasma glucose, and normoglycemia was produced within 78 +/- 37 minutes (mean +/- SD). However, once normoglycemia was achieved, brain glucose was still significantly greater by 44% than in nondiabetic rats (p = 0.015). Moreover, the ratio of brain to plasma glucose was more than 50% greater in diabetic than nondiabetic rats, irrespective of whether or not they received insulin (p less than 0.01). We conclude that measurement of blood or plasma glucose in diabetic subjects will tend to underestimate the amount of glucose in the brain and that this relationship is not influenced by acute insulin therapy.


Evidence for autoregulation of camR, which encodes a repressor for the cytochrome P-450cam hydroxylase operon on the Pseudomonas putida CAM plasmid.
The regulatory gene camR on the CAM plasmid of Pseudomonas putida (ATCC 17453) negatively controls expression of the cytochrome P-450cam hydroxylase operon (camDCAB) for the camphor degradation pathway and is oriented in a direction opposite to that of the camDCAB operon. In this study, we examined expression of the camR gene by monitoring the beta-galactosidase activity of camR-lacZ translational fusions in P. putida camR and camR+ strains. We found that the camR gene was autogenously regulated by its own product, CamR. To search for an operator site of the camR gene, a cam repressor (CamR)-overproducing plasmid, pHAOV1, was constructed by placing the camR gene under the control of a pL promoter. The translational initiation codon of CamR was changed by site-directed mutagenesis from GTG to ATG to improve translation efficiency. Judging from sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis, the CamR protein was expressed up to about 10% of the soluble protein of CamR-overproducing Escherichia coli JM83/pHAOV1 cells. Results of DNase I footprinting assays using the cell lysate indicated that the CamR repressor covered a single region between the camR gene and the camDCAB operon. Our findings also suggest that the camR gene autogenously regulates its own expression by binding of the gene product, CamR, to the operator, which also serves as an operator of the camDCAB operon.


[The traditional classification and genetic systematics of bacteria in the genus Lactobacillus].
The classification of bacteria of the genus Lactobacillus has virtually been constructed according to generally accepted peculiarities of the carbohydrate metabolism of the 3 selective groups. The information about the nucleotide contents of DNA (%GC) allows to divide all of 67 species included in the genus into 4 "nucleotide" group according to genosystematics principles. The first group species has %GC = first--49-53, second--42-46, third--34-41 and fourth--32-37. In this manner, it will be singled out 4 new genera in a new proposed family Lactobacillaceae comb.nov.: Thermobacterium comb.nov., Streptobacterium comb.nov., Mediumbacterium comb.nov., and Betabacterium comb.nov. correspondingly. For further revision of the systematics of the bacteria of the Lactobacillaceae family comb.nov. in the direction of approaching its to the natural one it is essential to study of the degree of genome similarities of species representatives within being outline 4 "nucleotide" group both the molecular hybridization using the specific DNA probes and the restriction analysis of the chromosomal DNA (dactyloscopy genome technique).


[Fluorescence analysis of oral squamous cell carcinoma with 5-aminolevulinic acid labeling].
Photodynamic diagnosis (PDD) is a form of cancer detection based on the administration of an exogenous photoactivated compound that accumulates in malignant cells, followed by appropriate photo-irradiation. 5-aminolevulinic acid (5-ALA), which is one of these compounds, is a prodrug of the photosensitizer protoporphyrin IX (PpIX). This report describes a spectroscopic study of 5-ALA-generated PpIX fluorescence in human oral cancer cell lines. After transplanting five human oral squamous carcinoma cell lines into scid mice, the degree of tumor differentiation was evaluated by hematoxylin-and-eosin staining. Two, one, and two cell lines were poorly, moderately, and well differentiated, respectively. Under cell culture conditions, well and moderately differentiated cancer cells showed higher positive staining rates of AE1/AE3 than poorly differentiated ones in immunohistochemistry. 5-ALA-induced PpIX fluorescence intensities of five cell lines, which were cultured in Dulbecco's Modified Eagle's Medium (DMEM) treated with or without deferoxamine mesylate (DFO), were measured. In all cell lines, the maximum 5-ALA-generated fluorescence intensity was found in the presence of DFO. The fluorescence intensity varied with the degree of tumor differentiation in the following order: poorly differentiated, moderately differentiated, well differentiated. These results suggest that the fluorescence intensity of oral cancer cells differs according to the degree of tumor differentiation. However, even with well differentiated cancer cells, addition of DFO could increase the photodynamic sensitivity of 5-ALA as a result of greater cellular accumulation of PpIX.


Protein phosphatase Pph3 and its regulatory subunit Psy2 regulate Rad53 dephosphorylation and cell morphogenesis during recovery from DNA damage in Candida albicans.
The ability of the pathogenic fungus Candida albicans to switch cellular morphologies is important for infection and virulence. Recent studies have revealed that C. albicans yeast cells can switch to filamentous growth under genotoxic stress in a manner dependent on the DNA replication/damage checkpoint. Here, we have investigated the functions of Pph3 (orf19.4378) and Psy2 (orf19.3685), whose orthologues in Saccharomyces cerevisiae mediate the dephosphorylation of the DNA damage checkpoint kinase Rad53 and the histone variant H2AX during recovery from DNA damage. Deleting PPH3 or PSY2 causes hypersensitivity to DNA-damaging agents, including cisplatin, methylmethane sulfonate (MMS), and UV light. In addition, pph3Δ and psy2Δ cells exhibit strong filamentous growth under genotoxic stress. Flow cytometry analysis shows that the mutant cells have lost the ability to adapt to genotoxic stress and remain arrested even after the stress is withdrawn. Furthermore, we show that Pph3 and Psy2 are required for the dephosphorylation of Rad53, but not H2AX, during DNA damage recovery. Taken together, these results show that C. albicans Pph3 and Psy2 have important roles in mediating genotoxin-induced filamentous growth and regulating Rad53 dephosphorylation.


Application of Predicted Collisional Cross Section to Metabolome Databases to Probabilistically Describe the Current and Future Ion Mobility Mass Spectrometry.
Metabolomics is a powerful phenotyping platform with potential for high-throughput analyses. The primary technology for metabolite profiling is mass spectrometry. In recent years, the coupling of mass spectrometry with ion mobility spectrometry (IMS) has offered the promise of faster analysis time and greater resolving power. Our understanding of the potential impact of IMS on the field of metabolomics is limited by availability of comprehensive experimental data. In this analysis, we use a probabilistic approach to enumerate the strengths and limitations, the present and future, of this technology. This is accomplished through use of "model" metabolomes, predicted physicochemical properties, and probabilistic descriptions of resolving power. This analysis advances our understanding of the importance of orthogonality in resolving (separation) dimensions, describes the impact of the metabolome composition on resolution demands, and offers a system resolution landscape that may serve to guide practitioners in the coming years.


[Comparative study on therapeutic effects of Baihui (GV 20), Shuigou (GV 26) and Shenmen (HT 7) in treatment of vascular dementia].
To compare the relative characteristics of Baihui (GV 20), Shuigou (GV 26) and Shenmen (HT 7) in treatment of vascular dementia. Fifty cases of vascular dementia (VD) were divided into 5 groups randomly. The patients in the group A were treated by acupuncture at routine acupoints. Besides the routine acupoints of the group A, Baihui (GV 20), Shuigou (GV 26) and Shenmen (HT 7) were added to treat the patients in group B, C, D, respectively, while Baihui, Shuigou and Shenmen were added to the group E. The clinical symptoms and signs were observed. Baihui and Shenmen can improve memory, orientation, reaction, obstinacy and trance of VD patients. Baihui is good at helping the patients to understand, calculate and adapt the society. Shuigou is good at improvement of sleeping, slow reaction, trance and memory of the patients. The combination of Baihui, Shuigou and Shenmen can generally promote intelligence level and society adaptive ability. Baihui, Shuigou and Shenmen have own characteristics in improving clinical signs and intelligence of patients of VD, and the combination of the 3 acupoints has the best effect in treating VD.


Legal restraints of pesticide effect on human organism and environment under international legislation.
Human health depends on many factors: a level of medicine, quality of medical preparations, state of the environment, food safety, lifestyle and others. Phytosanitary products including pesticides used by farmers to kill, control reproduction and prevent animal, microbial or plant pests in the cultivation of agricultural products, which are the basis of human food, are one of the factors that may have an unfavourable effect on human health. To analyze provisions of international legislation for presence of effective means to prevent a negative pesticide effect on human health and the environment. International acts, data of international organizations and conclusions of scientists have been examined and used in the study. The article also summarizes information from scientific journals and monographs from a medical and legal point of view with scientific methods. As a part of a systematic approach, issues of the pesticide effect in the course of their use on human health and the environment are analyzed. Based on the undertaken study, it has been found that developed countries take much better care of prevention and reduction of the negative pesticide effect on human health and the environment in the course of their use than developing countries. The pesticide effect has a dual nature. On the one hand, it is positive to ensure efficient development of agriculture, but on the other hand, it is negative that is expressed in potential possibilities of harm to humans and the environment.


Socially guided attention influences infants' communicative behavior.
For effective prelinguistic communication, infants must be able to direct their attention, vocalizations, and nonverbal gestures in social interactions. The purpose of our study was to examine how different styles of caregiver responses influenced infant attentional and communicative behavior in social interactions, based on prior studies that have shown influences of responsiveness on attention, language and cognitive outcomes. Infants were exposed to redirective and sensitive behavior systematically using an ABA design to examine real-time changes in infants' behavior as a function of caregiver responses. During the two baseline "A" periods, caregivers were instructed to play as they would at home. During the social response "B" period, caregivers were instructed to respond sensitively to infants' behavior on one visit and redirectively on the other visit. Results demonstrated that when caregivers behaved redirectively, infants shifted their attention more frequently and decreased the duration of their visual attention. Caregiver responses also resulted in changes in vocal and gesture production. Infants decreased their production of caregiver-directed vocalizations, gestures, and gesture-vocal combinations during in the redirective condition. Results suggest that caregiver sensitive responding to infants' attentional focus may be one influence on infants' attentional and prelinguistic communicative behavior.


Changes in the public perceptions of the health benefits of alcohol use, 1989 to 1994.
Data from a telephone survey of a national quota sample of the Australian community were used to assess changes in the public's perception of the benefits of alcohol use between 1989 and 1994, during which time there was media coverage of a debate about the health benefits of moderate alcohol consumption. The proportion identifying health benefits of alcohol use increased from 28 per cent in 1990 in New South Wales to 46 per cent in 1994 in Australia. The most commonly identified benefits of alcohol use remained relaxation (54 per cent), followed by cardiovascular benefits (39 per cent), which had not been mentioned in the previous survey. The likelihood of identifying any health benefits of alcohol use was higher among men than women, increased with age to the middle 30s, was higher among those with a tertiary education, and increased with frequency of alcohol use.


How Much More XXX is Generation X Consuming? Evidence of Changing Attitudes and Behaviors Related to Pornography Since 1973.
We use data from the General Social Survey (GSS) over a 40-year period (1973-2012) to evaluate changes in attitudes about pornography and pornography consumption among American young adults. One of the major challenges in making comparisons across birth generations is separating the effect of birth cohort from age and period effects. We use an intrinsic estimator to separately identify the effects of age, birth cohort, and time period using 40 years of repeated cross-section data. We find that, relative to the general population, young people's beliefs about whether pornography should be illegal have stayed relatively constant over this 40-year period and, if anything, have slightly increased. We also find that pornography consumption has been increasing across birth generations, though this increase has been smaller than would be inferred based on differences across generations at a single point in time, due to a strong age component in consumption patterns.


Different drives of herding: An exploratory study of motivations underlying social conformity.
We often align our behaviors, attitudes, and opinions in line with a majority of others, a phenomenon known as "social conformity." A seminal framework has proposed that conformity behaviors are mainly driven by three fundamental motives: a desire to gain more information to be accurate, to obtain social approval from others, and to maintain a favorable self-concept. However, previous studies usually have interpreted conformity behaviors as driven by one motive or another, largely ignoring the fact that human behaviors could be concurrently induced by multiple and even conflicting motivations. Adopting a typical conformity paradigm widely used in previous studies, we explored distinct and concurrent motives underlying the same conformity behavior, combining personality and individual differences with more nuanced analyses of observed conformity behaviors. Our findings provide novel evidence to show that three motivations exist within a single conformity behavior, suggesting that multiple motivations drive the conformity concurrently. These findings provide a potential solution for the extensive debate about what drives human social conformity and help to better understand the conformity behavior in daily life.


A framework for improving access and customer service times in health care: application and analysis at the UCLA Medical Center.
There has been an increasing emphasis on health care efficiency and costs and on improving quality in health care settings such as hospitals or clinics. However, there has not been sufficient work on methods of improving access and customer service times in health care settings. The study develops a framework for improving access and customer service time for health care settings. In the framework, the operational concept of the bottleneck is synthesized with queuing theory to improve access and reduce customer service times without reduction in clinical quality. The framework is applied at the Ronald Reagan UCLA Medical Center to determine the drivers for access and customer service times and then provides guidelines on how to improve these drivers. Validation using simulation techniques shows significant potential for reducing customer service times and increasing access at this institution. Finally, the study provides several practice implications that could be used to improve access and customer service times without reduction in clinical quality across a range of health care settings from large hospitals to small community clinics.


Thyroid hormone accelerates opsin expression during early photoreceptor differentiation and induces opsin switching in differentiated TRα-expressing cones of the salmonid retina.
Thyroid hormone and its receptors (TRs) regulate photoreceptor differentiation and visual pigment protein (opsin) expression in the retinas of several vertebrates, including rodents and fish. In some of these animals, opsin expression can arise through switches within differentiated cone photoreceptors. In salmonid fishes, single cones express ultraviolet (SWS1) opsin during embryonic development and switch to blue (SWS2) opsin as the fishes grow. It is unknown whether thyroid hormone regulates opsin expression during early cone differentiation and acts through TRs to induce opsin switches in differentiated cones of the salmonid retina. Using in situ hybridization, we characterized the spatiotemporal dynamics of opsin expression and switching in embryos treated with exogenous thyroid hormone or propylthiouracil (PTU), a pharmacological inhibitor of thyroid hormone synthesis. We combined immunohistochemistry with in situ hybridization to map TRα expression with respect to cones undergoing the opsin switch in older juvenile fish. Thyroid hormone accelerated opsin expression in differentiating cones and induced the opsin switch in differentiated single cones, whereas PTU repressed the opsin switch. TRα was not detected in differentiating photoreceptors as opsin expression initiated, but was later expressed in differentiated single cones before the onset of the opsin switch. TRα expression exhibited a dynamic dorsoventral distribution that paralleled the progression of the opsin switch. Together, our results show that thyroid hormone is required for opsin switching in the retina of salmonid fishes and suggest that TRα may be involved in regulating this phenomenon.