Eomesodermin requires transforming growth factor-beta/activin signaling and binds Smad2 to activate mesodermal genes.
The T-box gene Eomesodermin (Eomes) is required for early embryonic mesoderm differentiation in mouse, frog (Xenopus laevis), and zebrafish, is important in late cardiac development in Xenopus, and for CD8+ T effector cell function in mouse. Eomes can ectopically activate many mesodermal genes. However, the mechanism by which Eomes activates transcription of these genes is poorly understood. We report that Eomes protein interacts with Smad2 and is capable of working in a non-cell autonomous manner via transfer of Eomes protein between adjacent embryonic cells. Blocking of Eomes protein transfer using a farnesylated red fluorescent protein (CherryF) also prevents Eomes nuclear accumulation. Transfer of Eomes protein between cells is mediated by the Eomes carboxyl terminus (456-692). A carbohydrate binding domain within the Eomes carboxyl-terminal region is sufficient for transfer and important for gene activation. We propose a novel mechanism by which Eomes helps effect a cellular response to a morphogen gradient.


Short-term effects of the DASH diet in adults with moderate chronic kidney disease: a pilot feeding study.
Although the Dietary Approaches to Stop Hypertension (DASH) diet lowers blood pressure (BP) for adults with normal kidney function, evidence is lacking regarding its safety and efficacy in chronic kidney disease (CKD). We aimed to test the effects of the DASH diet on serum electrolytes and BP in adults with moderate CKD. In a prospective before-after feeding study, 11 adults with an estimated glomerular filtration rate of 30-59 mL/min/1.73 m(2) and medication-treated hypertension were provided a reduced-sodium, run-in diet for 1 week followed by a reduced-sodium, DASH diet for 2 weeks. Changes in serum electrolytes and BP were compared pre-post DASH. Eleven participants underwent feeding; 1 completed 1 week and 10 completed 2 weeks of DASH. Compared with baseline, DASH modestly increased serum potassium at 1 week (mean ± standard deviation, +0.28 ± 0.4 mg/dL; P = 0.043) but had no significant effect on potassium at 2 weeks (+0.15 ± 0.28 mg/dL; P = 0.13). Serum bicarbonate was reduced (-2.5 ± 3.0 mg/dL; P = 0.03) at 2 weeks. Neither incident hyperkalemia nor new onset metabolic acidosis was observed. Clinic BP and mean 24-h ambulatory BP was unchanged. DASH significantly reduced mean nighttime BP (-5.3 ± 5.8 mmHg; P = 0.018), and enhanced percent declines in both nocturnal systolic BP (-2.1% to -5.1%; P = 0.004) and diastolic BP (-3.7% to -10.0%; P = 0.008). These pilot data suggest that a reduced-sodium DASH dietary pattern does not cause acute metabolic events in adults with moderate CKD and may improve nocturnal BP. Definitive studies are needed to determine long-term effects of DASH in CKD.


Involvement of alanine 103 residue in kinetic and physicochemical properties of glucose isomerases from Streptomyces species.
The Ala103 to Gly mutation, introduced within the glucose isomerase from Streptomyces sp. SK (SKGI) decreased its catalytic efficiency (k(cat)/K(m)) toward D-glucose from 7.1 to 3 mM(-1) min(-1). The reverse counterpart replacement Gly103Ala introduced into the glucose isomerase of Streptomyces olivochromogenes (SOGI) considerably improved its catalytic efficiency to be 6.7 instead of 3.2 mM(-1) min(-1). This later mutation also increased the half-life time of the enzyme from 70 to 95 min at 80 degrees C and mainly modified its pH profile. These results provide evidence that the residue Ala103 plays an essential role in the kinetic and physicochemical properties of glucose isomerases from Streptomyces species.


Current advances in immunotherapy for atypical teratoid rhabdoid tumor (ATRT).
Atypical teratoid rhabdoid tumors (ATRT) are rare and aggressive embryonal tumors of central nervous system that typically affect children younger than 3 years of age. Given the generally poor outcomes of patients with ATRT and the significant toxicities associated with conventional multi-modal therapies, there is an urgent need for more novel approaches to treat ATRT, one such approach being immunotherapy. The recent rise of large-scale, multicenter interdisciplinary studies has delineated several molecular and genetic characteristics unique to ATRT. This review aims to describe currently available data on the tumor immune microenvironment of ATRT and its specific subtypes and to summarize the emerging clinical and preclinical results of immunotherapy-based approaches. It will also highlight the evolving knowledge of epigenetics on immunomodulation in this epigenetically influenced tumor, which may help guide the development of effective immunotherapeutic approaches in the future.


Low expression of p63 and p73 in osteosarcoma.
The recent discovery of two p53-related genes, p63 and p73, has revealed an additional level of complexity to the study of p53 function. Both genes encode multiple proteins arising from alternative promoter usage and splicing, with transactivation, DNA-binding, and tetramerization domains. Recent data support a role for p63 in squamous and transitional cell carcinomas, as well as in certain lymphomas and thymomas. To characterize the involvement of p63 and p73 in the development of osteosarcoma, we analyzed the expression and mutation of TAp63 and TAp73 in six osteosarcoma cell lines and twelve osteosarcoma specimens. Semiquantitative DNA/PCR analysis revealed that eight (67%) and six (50%) out of twelve osteosarcoma specimens showed significantly reduced levels of p63 and p73 transcription, respectively. Direct sequencing of the entire coding region detected no mutations in cell lines or osteosarcoma specimens. Our data suggest that low expression of p63 and p73 is relatively common in osteosarcomas and might contribute to their molecular pathogenesis.


Stress during a critical postnatal period induces region-specific structural abnormalities and dysfunction of the prefrontal cortex via CRF1.
During the early postnatal period, environmental influences play a pivotal role in shaping the development of the neocortex, including the prefrontal cortex (PFC) that is crucial for working memory and goal-directed actions. Exposure to stressful experiences during this critical period may disrupt the development of PFC pyramidal neurons and impair the wiring and function of related neural circuits. However, the molecular mechanisms of the impact of early-life stress on PFC development and function are not well understood. In this study, we found that repeated stress exposure during the first postnatal week hampered dendritic development in layers II/III and V pyramidal neurons in the dorsal agranular cingulate cortex (ACd) and prelimbic cortex (PL) of neonatal mice. The deleterious effects of early postnatal stress on structural plasticity persisted to adulthood only in ACd layer V pyramidal neurons. Most importantly, concurrent blockade of corticotropin-releasing factor receptor 1 (CRF1) by systemic antalarmin administration (20 μg/g of body weight) during early-life stress exposure prevented stress-induced apical dendritic retraction and spine loss in ACd layer V neurons and impairments in PFC-dependent cognitive tasks. Moreover, the magnitude of dendritic regression, especially the shrinkage of apical branches, of ACd layer V neurons predicted the degree of cognitive deficits in stressed mice. Our data highlight the region-specific effects of early postnatal stress on the structural plasticity of prefrontal pyramidal neurons, and suggest a critical role of CRF1 in modulating early-life stress-induced prefrontal abnormalities.


Use of soluble and Staphylococcus aureus-immobilized second antibody compared in a radioimmunoassay for human alpha-fetoprotein.
Staphylococcus aureus cells coated with rabbit anti-goat immunoglobulin G were compared with soluble second antibody in a radioimmunoassay for human serum alphafetoprotein. Recovery of primary immune complexes with use of the bacterial immunoadsorbant (a) allowed second-antibody incubation time to be shortened from 3 h to 20 min at 37 degrees C, (b) decreased by 80% the amount of second antibody required per assay, thereby significantly reducing assay costs, and (c) provided a convenient and reproducible method for separation of free and bound antigen. The ease of preparation and the uniformity and stability of the S. aureus second-antibody reagent are additional advantages that may be useful in other radioimmunoassay procedures.


Electroacupuncture and moxibustion attenuate the progression of renal disease in 5/6 nephrectomized rats.
Chronic kidney disease is a worldwide public health problem and the prevention of its progression is still a major challenge in nephrology. Specific therapies that inhibit or attenuate this process are neither available nor satisfactory. Traditional Chinese medicine has been increasingly recognized as an effective therapeutic approach in several fields of medicine. The aim of this study was to investigate the effects of electroacupuncture (EA) and moxibustion (MO) in an experimental model of progressive renal disease in rats. Twenty-one male Wistar rats were submitted to 5/6th nephrectomy (NX) and assessed 8 weeks later and were divided into three groups: NX = only 5/6 NX, NX-AS = 5/6 NX and a 20-min EA-MO session in sham points, and NX-AM = 5/6 NX and a 20-min EA-MO session in three real acupuncture points. The treatment consisted of 16 sessions twice a week. Renal function, urine volume, serum creatinine, 24-hour proteinuria, direct and indirect blood pressure, glomerulosclerosis and tubulointerstitial fibrosis indices were assessed. The NX-AM group showed a significant decrease in all investigated parameters when compared to the control groups. Our results suggest that EA and MO attenuated the progression of renal disease in the experimental model of 5/6 NX.


CHARGE association: histopathological report of two cases and a review.
The CHARGE association (C = coloboma, H = heart disease, A = atresia or stenosis of the choanae, R = retarded growth and development or CNS anomalies, G = genital hypoplasia, and E = ear anomalies or deafness) is a rare, recently well-recognized clinical study. The ophthalmic abnormalities have been described in numerous reports, but the ocular histopathologic findings have not been presented in detail. We conducted gross and microscopic studies of eyes of two patients with the CHARGE association obtained postmortem. The eyes in one case had a small, symmetrical, inferior nasal coloboma of the choroid. In the other case, extensive inferior nasal colobomas of the iris, ciliary body, and choroid with retinal dysplasia, ectopic retinal/glial tissue in the sclera and hypoplasia of the optic nerve head were present. We document the histopathological features of eyes of two subjects with the CHARGE association. The abnormalities of these eyes were typical ocular colobomas presumably resulting from the failure of complete closure of the optic fissure.


The development of imitation crab sticks by substituting spent laying hen meat for Alaska pollack.
Imitation crab stick (ICS) samples were divided into 5 treatments, a control composed of commercial ICS containing no breast meat from spent laying hens, and treatments 1, 2, 3, and 4, in which 5, 10, 15, and 20% batter from breast meat of whole spent laying hens was substituted for Alaska pollack surimi, respectively. Imitation crab stick samples containing spent laying hen breast meat batter showed significantly (P < 0.05) higher moisture levels than the control sample. However, the myoglobin and metmyoglobin levels did not differ significantly (P > 0.05) among ICS samples. During storage, whiteness was greater in the control sample than in the ICS samples containing spent laying hen breast meat batter. The saturated and monounsaturated fatty acids increased, whereas the polyunsaturated fatty acids decreased in response to substituting surimi with spent laying hen breast meat batter. The moisture content and pH were increased as the amount of spent laying hen breast meat batter increased. The lipid oxidation value (TBA-reactive substances) and protein degradation value (volatile basic nitrogen) tended to increase during storage as the amount of spent laying hen breast meat batter increased. None of the sensory evaluation items differed among ICS samples during storage, although the color of the final products, mechanical color (by colorimeter), and textural properties did differ among samples. These results indicate that substituting laying hen breast meat batter for Alaska pollack surimi is a very useful method for the production of ICS because it enables the use of a simple production process that does not require steps, such as washing or pH adjustment, for myofibrillar protein recovery.


[Measurement of low corrosion rate of coronary stents-made of 316L and 317L stainless steel].
Electrochemical constant current linear polarization and atomic absorption spectroscopy were used to measure the corrosion rate of coronary stents made of 316L and 317L stainless steel in 30 degrees C Tyrode's solution. The results indicated that the corrosion rate of 316L and 317L stainless steel was 21 X 10(-3) microm/a, 9.8 X 10(-3) microm/a and 0.8 X 10(-3) m/a, 0.6 X 10(-3) microm/a, respectively. All corrosion rates were lower than the medical materials corrosion rate criteria, i.e. 0.25 microm/a. Moreover the corrosion resistance of 317L stainless steel was much higher than that of 316L stainless steel. The results from atomic absorption spectroscopy may correctly reflect the quantity of releasing metal ions in the solution.


Epidemiology and management of splenic injury: An analysis of a Chinese military registry.
In China, there have been few meta-analyses of the epidemiology and management of splenic injury. Due to the success of Chinese military hospitals in the domestic treatment of splenic injury, the present study conducted a systematic review of such cases, identifying a high occurrence rate of splenic trauma, as well as a number of strategies of managing splenic injury in China. Data were collected from sixteen Chinese military hospitals between July 2000 and March 2009, and retrospectively reviewed. It was observed that between July 2000 and March 2009 a total of 7,807 patients (84.32% male and 15.68% female) with splenic injury were admitted to hospital. The mean duration of hospital stay was 17.9±18.6 days and the gender distribution of splenic injury over the successive years did not differ significantly (P>0.05, c=0.034). However, there was a significant difference in the gender distribution of splenic injury patients in different months (P<0.05, c=0.063). In addition, admission numbers for splenic injury were highest in September, October and November. It was also found that splenic injury may occur at all ages, though patients of working age (20-50 years), which comprises 85.59% of patients, the highest proportion of all recorded cases. Associations between mortality rate and each management strategy were as follows: Operative management, 0.11% and non-operative management, 0.15%. Furthermore, multivariate analysis demonstrated that transfusion, New Injury Severity Score and management strategies were all correlated with mortality rate. Thus, despite a lack of data for inpatients from civilian hospitals, the present study has, in part, identified the epidemiology and management strategies of splenic injury in China. These findings may supplement those from previous analyses of splenic injury in other countries and regions.


Use of amphotericin B in mucocutaneous leishmaniasis.
Twelve patients with South American mococutaneous leishmaniasis who attended the Hospital Amazonico in Peru between February and September 1974 were treated with amphotericin B. The lesions responded rapidly to treatment. A relatively low total dose of amphotericin B induced healing of active lesions. No serious adverse effects of treatment were encountered.


Orthopaedic training: 'run through' or uncoupled.
The Postgraduate Medical Education and Training Board wants either 'run through' or 'uncoupled' orthopaedic training to be adopted throughout the United Kingdom but it is not willing to let both continue together as is the current situation. This annotation explores the argument for and against 'run through' training.


Intestinal manometry: who needs it?
The use of manometry, i.e. the recording of pressures within hollow viscera, after being successfully applied to the study of esophageal and anorectal motor dysfunctions, has also been used to investigate physiological and pathological conditions of the small bowel. By means of this technique, it has been possible to understand better the normal motor functions of the small intestine, and their relationship and variations following physiologic events, such as food ingestion. Moreover, intestinal manometry has proved useful to document motor abnormalities of the small bowel, although recognition of altered patterns specific for a determinate pathologic condition is still unavailable. However, this technique often permits the detection of abnormal gut motility in patients with abdominal symptoms such as unexplained vomiting and diarrhea, and it is sometimes also useful to address therapeutic targeting.


Evaluation and characterization of anti-RalA autoantibody as a potential serum biomarker in human prostate cancer.
Autoantibodies against intracellular tumor-associated antigens (TAAs) are commonly found in human cancers. In this study, we characterized the serum autoantibody response to the RalA, Ras-like GTPase, in patients with prostate cancer (PCa). The autoantibodies were detected by immunofluorescence assay in PCa cell lines, ELISA, and immunoblotting in 339 serum samples from patients with PCa and benign prostatic hyperplasia (BPH), and in normal human sera (NHS). The expression of RalA in prostate tumor tissues was evaluated by immunohistochemistry (IHC) in tumor microarrays. The autoantibody level to RalA (median) in NHS was significantly lower than in PCa (0.053 vs 0.138; P < 0.001) and BPH (0.053 vs 0.132; P < 0.005) groups. The circulating anti-RalA autoantibody could distinguish PCa patients from normal individuals with the area under the receiver operating characteristic (ROC) curve (AUC) performing at 0.861, with sensitivity of 52.9% and specificity of 91.0%. Elevation in serum immunoreactivity was observed in PCa patients after radical prostatectomy. The combined use of both anti-RalA autoantibody and PSA showed a significantly higher discriminatory ability compared with either of those markers alone. RalA protein expression was detected by IHC in 85.3% of tumor tissues from PCa patients, but without significant difference compared to BPH or normal control tissues. Together, our study shows the additional benefits of anti-RalA autoantibody as a potential serological biomarker for PCa, particularly in patients with normal PSA, and further demonstrate the utility of biomarker combinations in the immunodiagnosis of PCa.


Regional variations in the female age at marriage in India: an analysis by agro-climatic zones.
"The effect of agro-climatic factors on female age at marriage [in India] is studied by carrying out areal analysis of the 1981 Census data. The study found a close association between agricultural and climatic conditions in an area and corresponding female age at marriage. In general, women in Himalayan regions and coastal areas have higher age at marriage than most hinterland regions. Rainfall, altitude, forest area, land availability and productivity are observed to be associated with female age at marriage. In addition, female age at marriage in rural areas is found to be more sensitive to the agro-climatic conditions. It is hypothesized that with socio-economic and technological development, the agricultural and climatic factors are losing their grip on female age at marriage in India."


Viral FLIP enhances Wnt signaling downstream of stabilized beta-catenin, leading to control of cell growth.
Death receptor-mediated apoptosis is potently inhibited by viral FLIP (FLICE/caspase 8 inhibitory protein), which is composed of two tandemly repeated death effector domains (DEDs), through reduced activation of procaspase 8. Here, we show that equine herpesvirus 2-encoded viral FLIP E8 enhances Wnt/beta-catenin signaling in a variety of cell lines. E8 was shown to strikingly augment Wnt3a signaling, as shown both in a luciferase assay for T-cell factor/beta-catenin and through induction of endogenous cyclin D1. The effect of E8 was independent of its direct binding activity with DED-containing signaling molecules, including caspase 8 and FADD, in death receptor-mediated apoptosis. E8 enhanced Wnt signaling downstream of stabilized beta-catenin, while a long form of cellular FLIP (c-FLIP(L)) enhanced stabilization of beta-catenin in 293T cells. Consequently, coexpression of E8 and c-FLIP(L) synergistically increased Wnt signaling in 293T cells. Moreover, E8-mediated stimulation of Wnt signaling induced dramatic growth retardation in untransformed cell lines but not in transformed cell lines. Thus, viral FLIP E8 not only inhibits death receptor-mediated apoptosis but also enhances Wnt signaling pathways that are closely related to those of both ontogenesis and oncogenesis.


Contribution of meals and snacks to nutrient intake of male and female elite figure skaters during peak competitive season.
To examine the contribution of breakfast, lunch, dinner and snack to the macronutrient and micronutrient intake of elite male and female figure skaters during their competitive season. Male (n = 46) and female (n = 48) figure skaters who participated in the 1999 U.S. National Figure Skating Championships completed the study. Each athlete completed three-day food records, during the athlete's competitive season. Food records were analyzed using Nutritionist V software. Macronutrient and micronutrient contributions from meals were assessed. Lunch and dinner meals were the main contributors to the total calorie intake of these skaters (27% and 32%, respectively). Likewise, lunch and dinner were the main contributors to the total protein (27% and 41%), carbohydrate (26% and 29%), fat (30% and 32%), saturated fat (29% and 32%) and polyunsaturated fat (31% and 32%) intakes. Dinner was the main source of the monounsaturated fat (34%), cholesterol (40%) and dietary fiber (34%). Breakfast was the main source of dietary folate (36%), whereas iron and calcium intakes were mainly contributed by breakfast and dinner (29% and 32%, 27% and 29%, respectively). These elite figure skaters appear to be starting their day with low energy reserves and therefore need to be educated about the benefits of consuming breakfast. These athletes also need to be educated about consuming adequate calories throughout the day in order to meet the energy needs of their activity. It is thus important to monitor eating patterns throughout the day to ensure adequate energy intake to sustain the physical and mental aspects of the athletes' training and performance.


Variations in genes regulating tumor-associated macrophages (TAMs) to predict outcomes of bevacizumab-based treatment in patients with metastatic colorectal cancer: results from TRIBE and FIRE3 trials.
Tumor-associated macrophages (TAMs) with the M2-like phenotype are regulated by mainly NF-kB pathway including TBK1, which can influence tumor progression by secretion of proangiogenic factors such as vascular endothelial growth factor. The CCL2/CCR2 axis, histidine-rich glycoprotein (HRG), and placenta growth factor (PIGF) play a critical role in the polarization of M1/M2 phenotypes and the recruitment of TAMs to tumor microenvironment. We therefore hypothesized that variations in genes involved in regulating TAMs may predict clinical outcomes of bevacizumab treatment in patients with metastatic colorectal cancer (mCRC). We analyzed genomic DNA extracted from samples of patients receiving bevacizumab plus FOLFIRI as a first-line treatment using PCR-based direct sequencing. Twelve functional single-nucleotide polymorphisms in eight genes (CCL2, CCR2, HRG, PIGF, NFKB1, TBK1, CCL18, and IRF3) were tested for associations with clinical outcomes in a discovery cohort of 228 participants in TRIBE trial (NCT00719797), then validated in 248 KRAS exon2 (KRAS) wild-type participants in FIRE3 trial (NCT00433927). FIRE3-cetuximab cohort served as a negative control. TBK1 rs7486100 was significantly associated with overall survival in 95 KRAS wild-type patients of TRIBE cohort in univariate analysis and had a strong trend in multivariable analysis; furthermore, the association of the T allele was observed for progression-free survival (PFS) in both univariate and multivariable analyses in FIRE3-bevacizumab but not cetuximab cohort. CCL2 rs4586, CCL18 rs14304, and IRF3 rs2304205 had univariate and multivariable correlations with PFS in KRAS mutant patients of the TRIBE cohort, whereas they had no correlations in KRAS wild-type patients of the TRIBE cohort. No association was seen in control cohort. Our study demonstrates for the first time that variations in genes regulating TAMs-related functions are significantly associated with clinical outcomes in mCRC patients treated with bevacizumab-containing chemotherapy. These results also suggest that some TAM-related gene variations may predict outcomes of bevacizumab treatment in KRAS status-dependent manner.


Ising fluids in an external magnetic field: an integral equation approach.
The phase behavior of Ising spin fluids is studied in the presence of an external magnetic field with the integral equation method. The calculations are performed on the basis of a soft mean spherical approximation using an efficient algorithm for solving the coupled set of the Ornstein-Zernike equations, the closure relations, and the external field constraint. The phase diagrams are obtained in the whole thermodynamic space including the magnetic field H for a wide class of Ising fluid models with various ratios R of the strengths of magnetic to nonmagnetic Yukawa-like interactions. The influence of varying the inverse screening lengths z(1) and z(2), corresponding to the magnetic and nonmagnetic Yukawa parts of the potential, is investigated too. It is shown that changes in R as well as in z(1) and z(2) can lead to different topologies of the phase diagrams. In particular, depending on the value of R, the critical temperature of the liquid-gas transition either decreases monotonically, behaves nonmonotonically, or increases monotonically with increasing H. The para-ferro magnetic transition is also affected by changes in R and the screening lengths. At H=0, the Ising fluid maps onto a simple model of a symmetric nonmagnetic binary mixture. For H--> infinity, it reduces to a pure nonmagnetic fluid. The results are compared with available simulations and the predictions of other theoretical methods. It is demonstrated that the mean spherical approximation appears to be more accurate compared with mean field theory, especially for systems with short ranged attraction potentials (when z(1) and z(2) are large). In the Kac limit z(1), z(2) -->+0, both approaches tend to nearly the same results.


Music Therapy for Coping Self-Efficacy in an Acute Mental Health Setting: A Randomized Pilot Study.
For adults with mental illness, coping skills represent an integral component of illness management and recovery (IMR) programs. Music therapy can be used to target IMR but empirical research specific to coping is needed. The purpose of this study was to determine if educational music therapy can influence coping self-efficacy in acute care mental health inpatients. Adults on an acute care mental health unit (N = 92) were cluster-randomized to one of three single-session conditions over 24 group-based sessions: educational lyric analysis, educational songwriting, or control. Although results were not significant, both educational music therapy conditions tended to have more favorable coping self-efficacy subscale means than the control condition but there were negligible differences between lyric analysis and songwriting conditions. Results can be considered clinically relevant within the temporal parameters of single-session therapy typical in acute care settings. Limitations, implications for practice, and suggestions for future research are included.


Transneuronal effects of early eye removal on geniculo-cortical projection cells.
Iontophoretic injections of horseradish peroxidase (HRP) were made into the primary visual cortex of normal rats, and into the visual cortex ipsilateral to the remaining eye of neonatally enucleated rats. The distribution of retrogradely labelled cells in the dorsal lateral geniculate nucleus (LGNd) in the two groups was compared. In normal animals labelled cells were found running in a discrete column through LGNd following the relevant line of projection. In enucleated animals the cells were less tightly grouped through the structure, although the lines of projection coursed in the same general direction. These results suggest that the consequences of early monocular enucleation upon the retinal projection from the remaining eye are transmitted beyond the regions receiving direct input from the eye to secondary visual projections.


Short femoral stem and porous titanium: winning combination?
A lot of different implants are available in hip replacement arthroplasty (THA), stems differ mainly by type of fixation, material, length, diameter, shape, surface coating, modularity, etc. The main quality of a non-cemented stem is to pursuit primary and secondary stability, to preserve bone stock, to be adaptable and modular. The literature shows that the most popular non cemented stems used in THA are metaphyseal femoral stem in which the distal portion has only the action to avoid varus stem placement but can also be a source of complications such as stress shielding. The stability of a short stem is closely dependent on material that must allow a high "scratch fit" and facilitate osteointegration with a generous surface of bone-implant contact. From September 2010 we have performed 287 THA using a modular titanium porous short stem. The article shows the preliminary results, which are very encouraging, showing excellent primary and secondary osteointegration, also slightly undersized implants or in elderly porotic patients.


Reagent-Controlled Regiodivergent Annulations of Achmatowicz Products with Vinylogous Nucleophiles: Synthesis of Bicyclic Cyclopenta[b]pyrans and 8-Oxabicyclo[3.2.1]octane Derivatives.
Two reagent-controlled regiodivergent annulation protocols for Achmatowicz products with vinylogous nucleophiles have been developed, which furnished a series of bicyclic cyclopenta[b]pyrans and 8-oxabicyclo[3.2.1]octane derivatives in 28-90% yields. Plausible mechanisms were proposed to involve either Pd-catalyzed Tsuji-Trost allyl-allyl coupling and concomitant Michael cyclization or quinine-promoted cascade stepwise [5 + 2] cycloaddition and intramolecular Michael cyclization.


Activity profiling of platelets by chemical proteomics.
Chemical proteomics or activity based proteomics is a functional proteomics technology where molecular probes are used to target a selective group of functionally related proteins. Its emergence has enabled specific targeting of subproteomes, overcoming the limitations in dynamic range of traditional large-scale proteomics experiments. Using a chemical proteomics strategy, we attempt to differentially profile the nucleotide-binding proteome of active and resting platelets. We apply an affinity chromatography protocol using immobilized adenosine triphosphate, cyclic adenosine monophosphate, and cyclic guanosine monophosphate. The specificity of the immobilized nucleotides was demonstrated by competitive assays and by immunoblotting. LC coupled MS/MS was applied to identify the proteins recovered by our chemical proteomics strategy. When compared to a standard set of platelet lysate proteins, we confirmed that enrichment for nucleotide-binding proteins was indeed taking place. Finally, by employing label-free MS-based comparative quantification, we found a small number of platelet proteins that show statistically significant difference between the active and resting nucleotide-binding proteome.


A psychoanalytic understanding of the desire for knowledge as reflected in Freud's Leonardo da Vinci and a memory of his childhood.
The author offers an understanding of the psychoanalytic notion of the desire for knowledge and the possibility of attaining it as it fi nds expression in Freud's Leonardo da Vinci and a memory of his childhood. This understanding has not been explicitly articulated by Freud but may be considered integral to psychoanalysis' Weltanschauung as shaped by Freud's legacy. It emerges through an attempt to explain basic shifts, contradictions, inconsistencies and tensions that become apparent from a close reading of the text of Leonardo. Articulating this implicit understanding of knowledge provides the grounds for a stance on epistemology that is integral to psychoanalysis and relevant to contemporary psychoanalytic concerns on this topic. This epistemology focuses on the necessary involvement of passion, rather than detachment, in the search for knowledge and views the psychoanalytic aim of self-knowledge as a derivative, and most immediate expression, of a broader and more basic human drive to know.


Investigation on the Pathological Mechanism of Frequent Exacerbators With Chronic Obstructive Pulmonary Disease Based on the Characteristics of Respiratory Flora.
Chronic obstructive pulmonary disease (COPD) is a common obstructive respiratory disease characterized by persistent respiratory symptoms and limited airflow due to airway obstruction. The present study investigates the distribution characteristics of respiratory tract flora in both frequent and infrequent exacerbators of COPD. The 16S sequencing technique was adopted to differentiate the inherent differences of respiratory tract flora between frequent exacerbators and infrequent exacerbators. Additionally, cell counting kit 8 (CCK8), lactate dehydrogenase (LDH) test, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and western blot were carried out in human bronchial epithelial cells cultured in vitro and the regulatory effects of differential flora were verified. The results revealed that the observed species index, Chao1 index, and the ACE estimator of COPD frequent exacerbators were markedly higher than those of COPD infrequent exacerbators. The top five strains of COPD frequent exacerbators included g_Streptococcus (15.565%), g_Prevotella (10.683%), g_Veillonella (6.980%), g_Haemophilus (5.601%), and g_Neisseria (4.631%). Veillonella parvula generated obvious cytotoxicity and substantially reduced the activity of human bronchial epithelial cells (p < 0.01). Furthermore, the results of flow cytometry indicated that the proportion of human bronchial epithelial cells in both the S phase and G2 phase decreased following Veillonella parvula treatment indicated that Veillonella parvula inhibited cell proliferation. Meanwhile, being treated using Veillonella parvula, the expressions of interleukin-1 (IL-1), IL-6, Tumor Necrosis Factor α (TNF-α), and p-nuclear factor kappa B (NF-κB) of the cells were increased markedly (p < 0.01). Taken together, the current research demonstrated that the relative abundance of Veillonella in COPD frequent exacerbators was higher than that of infrequent exacerbators. Veillonella parvula activated the inflammatory pathway, ultimately destroyed the cell viability, and greatly impaired the activity of human bronchial epithelial cells, thereby inhibiting cell proliferation.


INSPIRED Symposium Part 4B: Chimeric Antigen Receptor T Cell Correlative Studies-Established Findings and Future Priorities.
Chimeric antigen receptor (CAR) T cell therapy has revolutionized the treatment of B cell malignancies, with multiple CAR T cell products approved for numerous indications by regulatory agencies worldwide. However, significant work remains to be done to enhance these treatments. In March 2023, a group of experts in CAR T cell therapy assembled at the National Institutes of Health in Bethesda, Maryland at the Insights in Pediatric CAR T Cell Immunotherapy: Recent Advances and Future Directions (INSPIRED) Symposium to identify key areas for research for the coming years. In session 4B, correlative studies to be incorporated into future clinical trials and real-world settings were discussed. Active areas of research identified included (1) optimizing CAR T cell product manufacturing; (2) ensuring adequate lymphodepletion prior to CAR T cell administration; (3) overcoming immunoregulatory cells and tumor stroma present in the tumor microenvironment, particularly in solid tumors; (4) understanding tumor intrinsic properties that lead to CAR T cell immunotherapy resistance; and (5) uncovering biomarkers predictive of treatment resistance, treatment durability, or immune-related adverse events. Here we review the results of previously published clinical trials and real-world studies to summarize what is currently known about each of these topics. We then outline priorities for future research that we believe will be important for improving our understanding of CAR T cell therapy and ultimately leading to better outcomes for patients.


Redescription of a Hymenostome Ciliate, Tetrahymena setosa (Protozoa, Ciliophora) Notes on its Molecular Phylogeny.
In recent years, Tetrahymena species have been used as model organisms for research in a wide range of fields, highlighting the need for a fuller understanding of the taxonomy of this group. It is in this context that this paper uses living observation and silver staining methods to investigate the morphology and infraciliature of one Tetrahymena species, T. setosa (Schewiakoff 1892 Verh. Naturh. Med. Ver. Heidelb., 4:544) McCoy (1975) Acta Protozool., 14:253; the senior subjective synonym of T. setifera Holz and Corliss (1956) J. Protozool., 3:112; isolated from a freshwater pond in Harbin, north-eastern China. This organism can be distinguished from other described Tetrahymena species mainly by its single caudal cilium, which is about twice the length of the somatic ciliature. While the Harbin isolate appears similar to the population described by Holz and Corliss (1956) J. Protozool., 3:112, an improved diagnosis for T. setosa is given based on the previous descriptions and the Harbin population. In summary, this species can be recognized mainly by the combination of the following characters: body in vivo approximately 40 μm × 25 μm, 21-26 somatic kineties, one to four contractile vacuole pores associated with meridians 6-11 and a single caudal cilium. The small subunit ribosomal (SSU) rRNA gene and the cox1 gene sequences of Harbin population are also characterized in order to corroborate that the isolated species branches in phylogenetic trees as a T. setosa species. The phylogenetic analysis also indicated that sequences of populations of Tetrahymena species should be published with detailed morphological identifications.


Assessment of Cytotoxic, Genotoxic, and Oxidative Stress of Dibutyl Phthalate on Cultured Bovine Peripheral Lymphocytes.
Recently, there have been numerous reports showing that phthalates have negative human health impacts and may cause several diseases such as asthma, breast cancer, obesity, type II diabetes, and male infertility. Animals are also exposed to phthalates through the environment and can cause adverse health effects on them. Several studies have been found on the cytogenetic effects of dibutyl phthalate (DBP) on different organisms but no documented evidence has been found on the cytotoxic and genotoxic effects of dibutyl phthalate (DBP) on bovine cultured lymphocytes. MTT assay was performed on different series of DBP concentrations (10 μM, 20 μM, 30 μM, 50 μM, 70 μM, 100 μM). A concentration-dependent decrease in cell viability was observed by the DBP. The LD50, LD50/2, and 2∗LD50 were found to be 50 μM, 30 μM, and 80 μM on bovine lymphocytes, respectively. Then, these concentrations of DBP were utilized to perform comet, micronucleus assays, and oxidative stress. A concentration-dependent increase in DNA damage, oxidative stress, and micronuclei formation was observed in lymphocytes by the DBP as compared to the control group. Highest genotoxic effects were observed at a concentration of 2∗LD50. Similarly, total oxidative stress was found higher, and antioxidative stress was lower in concentration-dependent manner by the DBP. The current study revealed a significant cytotoxic, genotoxic, and oxidative stress of DBP on cultured bovine lymphocytes.


Structure of SARS-CoV-2 Spike Glycoprotein for Therapeutic and Preventive Target.
The global crisis caused by the coronavirus disease 2019 (COVID-19) led to the most significant economic loss and human deaths after World War II. The pathogen causing this disease is a novel virus called the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As of December 2020, there have been 80.2 million confirmed patients, and the mortality rate is known as 2.16% globally. A strategy to protect a host from SARS-CoV-2 is by suppressing intracellular viral replication or preventing viral entry. We focused on the spike glycoprotein that is responsible for the entry of SARS-CoV-2 into the host cell. Recently, the US Food and Drug Administration/EU Medicines Agency authorized a vaccine and antibody to treat COVID-19 patients by emergency use approval in the absence of long-term clinical trials. Both commercial and academic efforts to develop preventive and therapeutic agents continue all over the world. In this review, we present a perspective on current reports about the spike glycoprotein of SARS-CoV-2 as a therapeutic target.


Rarity of DNA sequence alterations in the promoter region of the human androgen receptor gene.
The human androgen receptor (AR) gene promoter lies in a GC-rich region containing two principal sites of transcription initiation and a putative Sp1 protein-binding site, without typical "TATA" and "CAAT" boxes. It has been suggested that mutations within the 5'untranslated region (5'UTR) may contribute to the development of prostate cancer by changing the rates of gene transcription and/or translation. In order to investigate this question, the aim of the present study was to search for the presence of mutations or polymorphisms at the AR-5'UTR in 92 prostate cancer patients, where histological diagnosis of adenocarcinoma was established in specimens obtained from transurethral resection or after prostatectomy. The AR-5'UTR was amplified by PCR from genomic DNA samples of the patients and of 100 healthy male blood donors, included as controls. Conformation-sensitive gel electrophoresis was used for DNA sequence alteration screening. Only one band shift was detected in one individual from the blood donor group. Sequencing revealed a new single nucleotide deletion (T) in the most conserved portion of the promoter region at position +36 downstream from the transcription initiation site I. Although the effect of this specific mutation remains unknown, its rarity reveals the high degree of sequence conservation of the human androgen promoter region. Moreover, the absence of detectable variation within the critical 5'UTR in prostate cancer patients indicates a low probability of its involvement in prostate cancer etiology.


Assessing adherence to antiretroviral therapy in randomized HIV clinical trials: a review of currently used methods.
Antiretroviral therapy for the treatment of HIV infection requires high levels of adherence to both maintain plasma HIV RNA at undetectable levels and prevent the emergence of drug resistance. As adherence to treatment is a major criterion for the evaluation of therapeutic outcomes, randomized clinical trials (RCTs) conducted among HIV-infected patients commonly include an assessment of adherence. However, there is still no gold-standard tool for assessing adherence behaviors in HIV RCTs. The methods currently used to collect and analyze adherence data are varied, which makes the comparison of results between studies difficult. The scope of this article is to review and discuss the range of adherence measures currently used in RCTs conducted among HIV-infected adults.


Common Pesticides Used in Suicide Attempts Following the 2012 Paraquat Ban in Korea.
To determine the change in pesticides used during suicide attempts after the 2012 paraquat (PQ) ban, we evaluated the annual number of suicide attempts by pesticide ingestion between 2011 and 2014. We extracted demographic, clinical outcome, and pesticide class data from the medical records of 1,331 patients that attempted suicide by pesticide ingestion. Pesticides were sorted into 5 groups: herbicides, insecticides, fungicides, other pesticides, and combined pesticides. Each group was subdivided into various classes based on publications by the respective Resistance Action Committees. The chi-square test for trends was used to compare the annual incidence of categorical variables. The total number of suicide attempts decreased each year, from 399 in 2011 to 245 in 2014. Simultaneously, PQ ingestion decreased from 253 patients in 2011 to 60 in 2014. The proportion of PQ to pesticides also decreased from 63.4% in 2011 to 24.5% in 2014. Furthermore, the rate of decrease in the proportion of PQ to all herbicide categories increased by calendar year. In conclusion, there is a significant trend in increased annual number of suicides and proportion of suicides using glyphosates and glufosinates versus total herbicides. However, the number of suicide attempts using glyphosate and glufosinate is lower than that using PQ. The ratio of persons completing suicide to those attempting suicide after pesticide ingestion has decreased every year after the PQ ban.


Roles of DNA methylation in influencing the functions of dental-derived mesenchymal stem cells.
DNA methylation as intensively studied epigenetic regulatory mechanism exerts pleiotropic effects on dental-derived mesenchymal stem cells (DMSCs). DMSCs have self-renewal and multidifferentiation potential. Here, this review aims at summarizing the research status about application of DMSCs in tissue engineering and clarifying the roles of DNA methylation in influencing the functions of DMSCs, with expectation of paving the way for its in-depth exploration in tissue engineering. The current research status about influence of DNA methylation in DMSCs was acquired by MEDLINE (through PubMed) and Web of Science using the keywords 'DNA methylation', 'dental-derived mesenchymal stem cells', 'dental pulp stem cells', 'periodontal ligament stem cells', 'dental follicle stem cells', 'stem cells from the apical papilla', 'stem cells from human exfoliated deciduous teeth', and 'gingival-derived mesenchymal stem cells'. This review indicates DNA methylation affects DMSCs' differentiation and function through inhibiting or enhancing the expression of specific gene resulted by DNA methylation-related genes or relevant inhibitors. DNA methylation can influence DMSCs in aspects of osteogenesis, adipogenesis, immunomodulatory function, and so on. Yet, the present studies about DNA methylation in DMSCs commonly focus on dental pulp stem cells (DPSCs) and periodontal ligament stem cells (PDLSCs). Little has been reported for other DMSCs.


Early postoperative adjustment of blepharoptosis.
The challenge of accurately predicting eyelid height after blepharoptosis surgery is a well-known problem even in competent hands. From May 1988 to December 2004, the authors reviewed 182 cases (240 eyes) of blepharoptosis corrected by frontalis muscle transfer or levator resection and had experienced 10 cases (15 eyelids) of early adjustment around 1 week. The period from initial operation to adjustment is between 6 and 8 days, and the mean period is 7 days. Initial operative procedures were frontalis muscle transfer in 3 cases (4 eyelids) and levator resection in 7 cases (11 eyelids). Follow-up period ranged from 6 months to 16 years. Early postoperative adjustment was performed in accordance with the preoperative and postoperative degree of ptosis of the patient and considering previous operative technique. The results are evaluated according to the criteria of an ideal correction by Souther and Jordan. Seven patients had good or satisfactory results (less than 1 mm asymmetry, good in 5 cases and satisfactory in 2 cases). Three patients (5 eyelids) were recorded as poor results (more than 2 mm asymmetry). Even if early or late reoperation can be effective in correcting unsatisfactory results after correction of blepharoptosis, early reoperation is better than later reoperation because early reoperation can offer a reduction in time to final result, the ease with which it is performed, potential cost savings. The experience of the surgeon is also an important factor for the treatment of recurred blepharoptosis.


Effects of various amino acids on methionine-induced hyperhomocysteinemia in rats.
Rats were fed diets supplemented with 1% L-methionine with and without 2.5% various amino acids for 7 d to determine what amino acids other than glycine, serine, and cystine can suppress methionine-induced hyperhomocysteinemia. L-Glutamic acid, L-histidine, and L-arginine significantly suppressed methionine-induced enhancement of plasma homocysteine concentrations, but the mechanisms underlying the effect of these amino acids are thought not to be identical.


Semiconductor self-assembled quantum dots: present status and future trends.
Progress in controlling the size, shape, and composition of quantum dots (QDs) as well as their positioning will be crucial to further advances in the fields of quantum information and device applications. The growth of QDs into lattices using controlled positioning of the QD nucleation centers is a possible method. QD positioning is also much needed for further development of QD microcavities and photonic-crystal based devices that are used for quantum information applications. This article discusses the prospects for progress in these fields that may be realized if a better control over the positioning and self-positioning of quantum dots is achieved.


Comparative Evaluation of the Microleakage and Shear Bond Strength of Three Filled Pit and Fissure Sealants Using Subpressure and Adhesive System: An Experimental Analysis.
Pit and fissure caries account for about 90% of caries in children and adolescents. Sealant application may be a preventive conservative approach. But it's still challenging to bolster the retention of the filled sealant and to chop back the microleakage. Aim is to evaluate and compare the microleakage and shear bond strength (SBS) of three filled pit and fissure sealants (PFS) using a subpressure and adhesive system: an experimental analysis. A total of 90 orthodontically extracted premolars were prepared for microleakage and SBS and divided according to materials and subgroups. Group I: resin-based filled PFS, group II: resin-modified glass ionomer-based filled PFS, and group III: giomer-based filled PFS. Subgroup 1: only sealant application, subgroup 2: subpressure application, and subgroup 3: adhesive system + subpressure application. Samples were subjected to thermocycling. Microleakage was assessed with a dye penetration method under a stereomicroscope, and SBS was assessed with a universal testing machine. Unpaired t-test and one-way analysis of variance (ANOVA) test were used for analysis. Significant when p < 0.05. The SBS showed significant results for subpressure application and giomer-based filled PFS with p < 0.05. The microleakages score differed significantly for the subpressure application group with p < 0.05. Giomer-based filled PFS showed the least microleakage score. This study concluded that giomer-based filled PFS showed statistically significant results. The subpressure technique significantly reduces microleakage and increases SBS. Waghmode SK, Devendrappa SN, Hadakar SG, et al. Comparative Evaluation of the Microleakage and Shear Bond Strength of Three Filled Pit and Fissure Sealants Using Subpressure and Adhesive System: An Experimental Analysis. Int J Clin Pediatr Dent 2023;16(S-1):S97-S100.


Routine HIV testing in men who have sex with men: from risk to prevention.
We conducted a critical review of the literature on recurrent use of HIV testing in men who have sex with men (MSM). We performed a narrative review of the literature in which we analyzed the various conceptions on frequent testing over time, the implications for health programs, and the main social markers that influence the incorporation of HIV testing as routine care. Although it has existed since the 1990s, recurrent testing among MSM was frequently interpreted as increased exposure to HIV due to lack of condom use, and therefore as "unnecessary" testing. Beginning in the 2000s, periodic testing has become a programmatic recommendation and has been interpreted as a goal. Individuals' perception of their use of the test has rarely been considered in order to characterize such use as routine care. On the social and cultural level, individual aspects associated with recent or routine testing were included in contexts of favorable norms for testing and less AIDS stigma. Differences in generation, schooling, and types of affective-sexual partnerships play an important part in testing. Such differences highlight that the epidemiological category "men who have sex with men" encompasses diverse relations, identities, and practices that result in specific uses of the test as a prevention strategy. Thus, dialogue between programs, health professionals, and the persons most affected by the epidemic is crucial for building responses with real potential to confront the HIV epidemic, based on respect for human rights.


Biogenic silver nanoparticles with chlorogenic acid as a bioreducing agent.
We report the synthesis of biogenic silver nanoparticles using chlorogenic acid as a bioreducing agent. Chlorogenic acid is a polyphenol compound abundant in coffee. UV-Vis spectra showed the characteristic surface plasmon resonance band at 415 nm, indicating the successful synthesis of biogenic silver nanoparticles. Spherical and irregular shaped nanoparticles were observed with an average diameter of 19.29 +/- 8.23 nm. The reaction yield from silver ion to silver nanoparticles was observed as 95.43% by using inductively coupled plasma-mass spectrometry. Fourier transform infrared spectra revealed that the -C = O groups of chlorogenic acid may coordinate or complex into silver nanoparticles. Biogenic silver nanoparticles exerted higher antibacterial activity against Gram-negative bacteria than against Gram-positive bacteria. Interestingly, a comparable antibacterial activity to a standard antibiotic was observed against two strains of Pseudomonas aeruginosa (minimum inhibitory concentration of 0.66 microg/mL). The synergistic effect of a combination of silver nanoparticles and chlorogenic acid on antibacterial activity is obvious, leading to approximately 8-fold enhancement in the case of Pseudomonas aeruginosa when compared with chlorogenic acid alone. The present report suggests that a pure compound with a plant origin is capable of being a bioreducing agent for the synthesis of biogenic silver nanoparticles with superior antibacterial activity, opening up many applications in nanomedicine and nanobiotechnology.


Community Perspectives on Hearing Loss in Rural Alaska.
The aim of this study is to present an explanatory model of hearing loss in the Bering Strait region of Alaska in order to contextualize the results of a cluster randomized trial and propose implications for regional hearing-related health care. To promote ecological validity, or the generalizability of trial findings to real world experiences, qualitative methods (focus groups and interviews) were used within a mixed methods cluster randomized trial evaluating school hearing screening and follow-up processes in 15 communities in the Bering Strait region of Alaska. Focus groups were held between April and August 2017, and semistructured interviews were conducted between December 2018 and August 2019. Convenience sampling was used for six of the 11 focus groups to capture broad community feedback. Purposive sampling was used for the remaining five focus groups and for all interviews to capture a variety of experiences with hearing loss. Audio recordings of focus groups and interviews were transcribed, and both notes and transcripts were deidentified. All notes and transcripts were included in the analysis. The constant comparative method was used to develop a codebook by iteratively moving between transcripts and preliminary themes. Researchers then used this codebook to code data from all focus groups and interviews using qualitative analysis software (NVIVO 12, QSR International) and conducted thematic analyses to distill the findings presented in this article. Participants in focus groups (n = 116) and interviews (n = 101) shared perspectives in three domains: etiology, impact, and treatment of hearing loss. Regarding etiology, participants emphasized noise-induced hearing loss but also discussed infection-related hearing loss and various causes of ear infections. Participants described the impact of hearing loss on subsistence activities, while also detailing social, academic, and economic consequences. Participants described burdensome treatment pathways that are repetitive and often travel and time intensive. Communication breakdowns within these pathways were also described. Some participants spoke positively of increased access via onsite hearing health care services in "field clinics" as well as via telemedicine services. Others described weaknesses in these processes (infrequent field clinics and communication delays in telemedicine care pathways). Participants also described home remedies and stigma surrounding the treatment for hearing loss. Patient-centered health care requires an understanding of context. Explanatory models of illness are context-specific ways in which patients and their networks perceive and describe the experience of an illness or disability. In this study, we documented explanatory models of hearing loss to foster ecological validity and better understand the relevance of research findings to real-life hearing-related experiences. These findings suggest several areas that should be addressed in future implementation of hearing health care interventions elsewhere in rural Alaska, including management of repetitious treatments, awareness of infection-mediated hearing loss, mistrust, and communication breakdowns. For hearing-related health care in this region, these findings suggest localized recommendations for approaches for prevention and treatment. For community-based hearing research, this study offers an example of how qualitative methods can be used to generate ecologically valid (i.e., contextually grounded) findings.


Inhibited angiogenesis in aging: a role for TIMP-2.
Factors responsible for age-associated impairment of angiogenesis are poorly understood. We observed that in aged mice, new fibrovascular tissue within subcutaneous polyvinyl alcohol sponges expressed more tissue inhibitor of metalloproteinases (TIMP)-2 than did corresponding tissue from young mice. In complementary studies in vitro, we utilized young and aged human microvascular endothelial cell lines (hmEC36 and hmEC90, respectively) and compared their morphogenetic capacity within three-dimensional collagen. HmEC90 exhibited poor formation of tubular, capillary-like structures in vitro, diminished expression of active matrix metalloproteinase (MMP)-2, and similar or lesser amounts of MT1-MMP relative to hmEC36. Correspondingly, the MMP inhibitor GM6001 decreased tubulogenesis by hmEC36 to levels observed for hmEC90. In vitro, hmEC90 expressed similar quantities of TIMP-1, but more TIMP-2 than did hmEC36. Accordingly, purified TIMP-2 inhibited tubulogenesis by hmEC36. Collectively, our studies indicate that elevated levels of TIMP-2 modulate decreased angiogenesis in aged tissues, most likely via TIMP-2-mediated inhibition of MMP-2 and MT1-MMP.


[Sturge-Weber syndrome: medical management of choroidal hemangiomas].
To investigate the outcome of irradiation of complicated choroidal hemangiomas in Sturge-Weber syndrome. The charts of 6 patients (7 eyes) with Sturge-Weber syndrome and choroidal hemangiomas were reviewed. An exudative retinal detachment was the indication for treatment in all cases. The mean age of the 6 patients was 13 years (range, 4 to 20 years). The minimum follow-up time was 1 year. Patients were checked for initial and final best-corrected visual acuity, fundus examination, fluorescein angiography, and tumor thickness on B-scan ultrasonography. The patients were treated with radiotherapy. A total dose of 20 Grays was applied to 7 eyes: 2 with a circumscribed choroidal hemangioma underwent proton therapy and 5 with diffuse hemangioma were treated by external beam irradiation. Complete resolution of the subretinal fluid was achieved in all cases with the tumor height decreased. Visual acuity improved to 1 line or more in 5 eyes and remained stable in 2 eyes. Two cases that underwent proton therapy developed radiation retinopathy. External beam radiation is an effective and safe option in the management of choroidal hemangiomas complicated by retinal detachment. Based on our experience, proton therapy should be reserved for sporadic circumscribed choroidal hemangioma.


Factors that contribute to posttherapy persistence of therapeutic change.
Studied 30 outpatient, psychotherapy clients and assessed their relative change of status at termination and 6-months posttreatment. The vast majority of clients indicated improvement during the treatment period. A majority maintained or continued to make gains during the posttherapy period. Socioeconomic status, age, total psychotherapy sessions, initial neuroticism, and initial extraversion were identified as predictors of positive change in status at termination and follow-up. Socioeconomic status, negative life events, marital change, total psychotherapy sessions, initial neuroticism, and age were identified as variables that discriminated between those individuals who did and did not improve.


Pharmacovigilance Considerations for Biosimilars in the USA.
In 2015, five or more biosimilars may be approved in the USA. Because no two biologic medicines are identical, postapproval safety monitoring will be critical to detect potential differences in safety signals between a biosimilar, its reference product, and other biosimilars. Postapproval safety monitoring in the USA uses two signal detection systems: spontaneous reporting systems (SRSs) and active surveillance (AS) systems. Both depend on accurate identification of the specific product(s) dispensed or administered to patients, which may be compromised when products from multiple manufacturers share common drug nomenclature or coding. Product identification can present challenges across different healthcare settings, including inpatient and ambulatory care. Common oral-dosage drugs are predominantly dispensed directly to patients by pharmacists, whereas most injectable drugs, including biologics, are administered to patients by healthcare professionals in outpatient clinics or hospitals. Thus, the effectiveness of SRS and AS mechanisms in both pharmacy and medical channels must be given greater consideration as biotechnology matures. In this article, we describe these systems and their limitations. We identify challenges and opportunities for product-specific safety surveillance of biologics in both the pharmacy and medical settings and provide recommendations to improve biologic safety surveillance under the current and future systems envisioned in the Drug Quality and Security Act. As biosimilars are integrated into existing pharmacovigilance systems, distinguishable nonproprietary names and codes for all biologics, as well as other opportunities to improve traceability (e.g., increased use of barcodes), must be considered to ensure patient safety and confidence in this new class of drugs.


Biodegradable Janus nanoparticles for local pulmonary delivery of hydrophilic and hydrophobic molecules to the lungs.
The aim of the present work is to synthesize, characterize, and test self-assembled anisotropic or Janus particles designed to load anticancer drugs for lung cancer treatment by inhalation. The particles were synthesized using binary mixtures of biodegradable and biocompatible materials. The particles did not demonstrate cyto- and genotoxic effects. Janus particles were internalized by cancer cells and accumulated both in the cytoplasm and nuclei. After inhalation delivery, nanoparticles accumulated preferentially in the lungs of mice and retained there for at least 24 h. Two drugs or other biologically active components with substantially different aqueous solubility can be simultaneously loaded in two-phases (polymer-lipid) of these nanoparticles. In the present proof-of-concept investigation, the particles were loaded with two anticancer drugs: doxorubicin and curcumin as model anticancer drugs with relatively high and low aqueous solubility, respectively. However, there are no obstacles for loading any hydrophobic or hydrophilic chemical agents. Nanoparticles with dual load were used for their local inhalation delivery directly to the lungs of mice with orthotopic model of human lung cancer. In vivo experiments showed that the selected nanoparticles with two anticancer drugs with different mechanisms of action prevented progression of lung tumors. It should be stressed that anticancer effects of the combined treatment with two anticancer drugs loaded in the same nanoparticle significantly exceeded the effect of either drug loaded in similar nanoparticles alone.


Immunomodulatory therapy for melanoma: ipilimumab and beyond.
In 2011, the U.S. Food and Drug Administration approved the first new therapy for melanoma in more than a decade, ipilimumab (Yervoy). Ipilimumab is a novel antibody that blocks cytotoxic T lymphocyte-associated antigen 4 (CTLA-4), a regulatory molecule expressed on activated T cells. Blockade of this important immune checkpoint can lead to durable tumor regression, and phase III studies show an overall survival benefit for patients with advanced melanoma. During the clinical development of ipilimumab, several unique features of this immunotherapy were identified, including the remarkable durability of responses and a distinct side-effects profile. We review the preclinical and clinical development of CTLA-4-blocking antibodies and describe current practices using ipilimumab for the treatment of advanced melanoma. Unique clinical issues related to ipilimumab will be summarized. Lastly, we will briefly preview combination therapies that incorporate ipilimumab and new checkpoint-targeting antibodies currently in clinical development.


Determination and comparison of alkaloids and triterpenes among tissues after oral administration of crude and processed Phellodendri Chinensis Cortex by UPLC-QqQ-MS.
Phellodendri Chinensis Cortex is widely used in the clinic of traditional Chinese medicine. In order to enlarge the range of application, it is necessary to processed with honey, salt-water, and rice-wine, respectively. We hope to elucidate the connotation of processing, an UPLC-QqQ-MS method was used for determination and comparison the tissue distribution of alkaloids and triterpenes after oral administration water-extracts of crude and processed products. The results showed that the berberine, phellodendrine, magnoflorine, limonin, and obacunone in crude and processed products were distributed in all tissues, especially in the small intestine and stomach. In this study, we can provide a scientific basis for explaining the processing connotation of Phellodendri Chinensis Cortex processed with salt-water and rice-wine, respectively.


Force sensor characterization under sinusoidal excitations.
The aim in the current work is the development of a method to characterize force sensors under sinusoidal excitations using a primary standard as the source of traceability. During this work the influence factors have been studied and a method to minimise their contributions, as well as the corrections to be performed under dynamic conditions have been established. These results will allow the realization of an adequate characterization of force sensors under sinusoidal excitations, which will be essential for its further proper use under dynamic conditions. The traceability of the sensor characterization is based in the direct definition of force as mass multiplied by acceleration. To do so, the sensor is loaded with different calibrated loads and is maintained under different sinusoidal accelerations by means of a vibration shaker system that is able to generate accelerations up to 100 m/s2 with frequencies from 5 Hz up to 2400 Hz. The acceleration is measured by means of a laser vibrometer with traceability to the units of time and length. A multiple channel data acquisition system is also required to simultaneously acquire the electrical output signals of the involved instrument in real time.


Constitutively active TRPC channels of adipocytes confer a mechanism for sensing dietary fatty acids and regulating adiponectin.
Calcium entry is pivotal in the heart and blood vessels, but its significance and mechanisms in adipose tissue are largely unknown. An important factor produced by adipocytes is adiponectin, which confers myocardial protection, insulin-sensitization, and antiatherosclerotic effects. To investigate the relevance of calcium channels to adipocytes and the production of adiponectin. Microarray analysis led to identification of transient receptor potential canonical (TRPC)1 and TRPC5 as channel subunits that are induced when adipocytes mature. Both subunits were found in perivascular fat of patients with atherosclerosis. Intracellular calcium and patch-clamp measurements showed that adipocytes exhibit constitutively active calcium-permeable nonselective cationic channels that depend on TRPC1 and TRPC5. The activity could be enhanced by lanthanum or rosiglitazone, known stimulators of TRPC5 and TRPC5-containing channels. Screening identified lipid modulators of the channels that are relevant to adipose biology. Dietary ω-3 fatty acids (eg, α-linolenic acid) were inhibitory at concentrations that are achieved by ingestion. The adipocyte TRPC1/TRPC5-containing channel was functionally negative for the generation of adiponectin because channel blockade by antibodies, knock-down of TRPC1-TRPC5 in vitro, or conditional disruption of calcium permeability in TRPC5-incorporating channels in vivo increased the generation of adiponectin. The previously recognized capability of α-linolenic acid to stimulate the generation of adiponectin was lost when calcium permeability in the channels was disrupted. The data suggest that TRPC1 and TRPC5 contribute a constitutively active heteromultimeric channel of adipocytes that negatively regulates adiponectin and through which ω-3 fatty acids enhance the anti-inflammatory adipokine, adiponectin.


The Memory Quilt: Heart-and-Hands Learning for Palliative Care.
Nursing students' learning of adult and pediatric palliative care is a daunting experience. An effective initial teaching strategy using a Memory Quilt activity can improve nursing students' interpersonal and communication skills and help prepare them for end-of-life caring. These skills help students meet patient and family needs, as they transition to care settings.


Performance characteristics of modern self-expanding nitinol stents indicated for SFA.
To evaluate performance characteristics of currently available superficial femoral artery (SFA) stents and stent delivery systems (SDS). Six 7 mm/ 80 mm stent systems were included: BIOTRONIK Astron Pulsar (4F), EDWARDS LifeStent Flexstar, ev3 PROTÉGÉ Everflex, CORDIS Smart Control, BARD E-Luminexx, GUIDANT Absolute (all 6F). The SDS were evaluated for profile, flexibility in the stent region, trackability and pushability through a tortuous vessel model and release force during deployment. The stents were evaluated for flexibility, radial force during expansion and compression, and shortening. The 4F system had a profile of 1.45 mm, and the 6F stent systems had a profile of 1.96 - 2.10 mm. The Astron Pulsar was most flexible (195 Nmm (2)) compared to 334 - 972 Nmm (2) for the 6F systems. The track force of the stiffest system (Flexstar, 0.314N) was higher than that of the Astron Pulsar (0.273N) but lower than that of the other systems (0.387 - 0.579N). The release force was 1.69N (Absolute), 2.05N (Astron Pulsar) up to 13.00N (Flexstar). The radial force for a 6 mm stent diameter during expansion ranged from 3.95N (Absolute) and 3.99N (Astron Pulsar) up to 7.22N (FlexStar) but was higher when compressed. The 4F system had the best flexibility and trackability. The release force was high in most systems with release handles. The radial force of all tested stents covers a broad range. These results could be helpful to find the best stent for different lesions.


Haloperidol inhibition of monoamine oxidase in vivo and in vitro.
Haloperidol was found to inhibit monoamine oxidase (MAO) activity in sonicated platelets by 50% (IC50) at a concentration of 10(-4) M. Preincubation of the sonicated platelets with haloperidol before the assay did not shift the dose-response curve. When cultured human skin fibroblast MAO was assayed along with haloperidol, MAO activity was only slightly affected (estimated IC50 = 3 X 10(-2) M), even with 1 hr of preincubation. When fibroblasts were cultured with medium containing haloperidol, however, the haloperidol IC50 for MAO activity was 3 X 10(-7) M after 3 days, 2 X 10(-8) M after 7 days, and 3 X 10(-9) M after 14 days. We conclude that haloperidol alters MAO enzyme activity acutely in vitro and that the inhibition increases at lower concentrations with chronic treatment in vivo.


The incidence of low back pain in ncaa division iii female field hockey players.
The authors speculated that there may be an increased incidence of low back pain (LBP) in NCAA Division III female field hockey (FH) players. FH players may experience LBP for a variety of reasons including trauma from collisions or falls. Excluding these types of direct trauma, FH players may experience LBP due to excessive stress to spinal structures related to the forward flexed posture that predominates in field hockey. The authors speculated that because of the postural stresses inherent to field hockey there may be an increased incidence of LBP in this population. Therefore, the purpose of this study was to survey NCAA Division III female FH players and an age matched control group to determine if field hockey participation results in an increased incidence of LBP. The anticipated finding of an increased incidence of LBP would provide a rationale for the development of prophylactic interventions for this population. Female NCAA Division III FH players (n=90) ranging in age from 18-24 years old who participated in the 2008 season were surveyed in regards to the incidence of LBP. A female age-matched control group from Misericordia University (n=98) without a history of field hockey participation was also surveyed. Both groups of subjects completed a voluntary pen and paper survey on the incidence of LBP not related to menstruation. Questions included but were not limited to; whether a significant episode of LBP had been experienced, the mechanism or injury, the duration and nature/location of symptoms. Responses from both groups were anonymous and confidential. There was no difference in the incidence of LBP between the female FH players and the control group (p=0.951). The incidence of LBP was 56% (50/90) in the female FH players and 55% (54/98) in the controls. There was no difference in pain characteristics including pain referral patterns between the 2 groups. However, survey responses revealed a similar mean age of onset of LBP for both groups (16.23 +/- 1.80 years of age for FH players and 16.45 +/- 2.12 years of age for controls). The data did not support the authors' speculation of a higher incidence of LBP in NCAA Division III female FH players compared to female age-matched controls. This suggests postures associated with field hockey do not appear to significantly increase the incidence of LBP in this population. However, the data revealed that females from both surveyed groups experienced an onset of LBP at a mean age of sixteen. 2b.


Muscle Activity in Pre-Treatment and Post-Treatment Oral Submucous Fibrosis Patients: Electromyography Study.
Oral submucous fibrosis (OSMF) is a premalignant condition of insidious onset which affects the oral mucosa, pharynx, and esophagus. The muscles of mastication are known to be affected resulting in limited mouth opening. Electromyography (EMG) is a sophisticated method of measuring and evaluating muscle activity. Previously, EMG was primarily utilized in medical sciences, but it is currently being used extensively in both the medical and dentistry fields. The aim of the study is to evaluate the electromyographic activity of masseter muscle in OSMF patients before and after treatment and to compare with healthy controls. This prospective case-control clinical study comprised 180 OSMF patients who were divided into four groups and 45 healthy individuals served as the control group. The OSMF individuals were injected with hyaluronidase 1,500 IU mixed in 1.5 ml of dexamethasone and 0.5 ml of lignocaine HCL intralesionally twice a week for one month along with a basic physiotherapy regimen consisting of mouth exercises two times daily. The control subjects were given placebo capsules. The treatment was carried out for a month and the electromyographic masseter muscle activity was evaluated among the OSMF patients and control group before and after treatment. The results revealed that the electromyographic activity of master muscles in OSMF patients showed increased activity when compared with healthy controls. Patients with OSMF showed decreased muscle activity after treatment. When compared with healthy controls, OSMF patients had higher electromyographic activity of the masseter muscles and the muscle activity was decreased following treatment. In OSMF patients, EMG may help in determining the involvement of the mastication and facial expression muscles. It can also be used as a diagnostic tool to assess the treatment outcome of muscle activity in OSMF patients.


Multiple testing in large-scale genetic studies.
Recent advances in Molecular Biology and improvements in microarray and sequencing technologies have led biologists toward high-throughput genomic studies. These studies aim at finding associations between genetic markers and a phenotype and involve conducting many statistical tests on these markers. Such Please confirm the changes in the sentence "Such a wide..." a wide investigation of the genome not only renders genomic studies quite attractive but also lead to a major shortcoming. That is, among the markers detected as associated with the phenotype, a nonnegligible proportion is not in reality (false-positives) and also true associations can be missed (false-negatives). A main cause of these spurious associations is due to the multiple-testing problem, inherent to conducting numerous statistical tests. Several approaches exist to work around this issue. These multiple-testing adjustments aim at defining new statistical confidence measures that are controlled to guarantee that the outcomes of the tests are pertinent.The most natural correction was introduced by Bonferroni and aims at controlling the family-wise error-rate (FWER) that is the probability of having at least one false-positive. Another approach is based on the false-discovery-rate (FDR) and considers the proportion of significant results that are expected to be false-positives. Finally, the local-FDR focuses on the actual probability for a marker of being associated or not with the phenotype. These strategies are widely used but one has to be careful about when and how to apply them. We propose in this chapter a discussion on the multiple-testing issue and on the main approaches to take it into account. We aim at providing a theoretical and intuitive definition of these concepts along with practical advises to guide researchers in choosing the more appropriate multiple-testing procedure corresponding to the purposes of their studies.


Pericardial teratoma: prenatal diagnosis and course.
We report on a case of primary pericardial teratoma detected in a 29-week-old fetus. Due to cardiac decompensation, pericardiocentesis was performed at 33 weeks of gestation, and surgical excision of the tumor was indicated shortly after birth. The present report draws attention to the impact of fetal echocardiography on perinatal management.


Pituitary Hyperplasia in a Female Patient with a Severe Childhood Abuse History.
A 24-year-old Caucasian female patient was referred to our endocrinology service to investigate a structural magnetic resonance imaging (sMRI) finding of "pituitary mass". The first two sMRI were identified as pituitary adenoma but the following two examinations suggested the possibility of pituitary hyperplasia (PH). The patient was referred to our service for diagnostic clarification and therapy due to the divergence in sMRI reports and the surgical procedure indicated by the neurosurgical team of the other institution. The patient had no complaints, laboratory tests were all normal, and the sMRI clearly showed a PH. However, what caught our attention was her behavior. During the interview she was intermittently talking and acting like a child even though her age was 24. She reported being a foster child and was severely mistreated during childhood. Parallel psychiatric evaluation was requested and an association between the PH and the childhood abuse was identified. Early life stress may be associated with accelerated pituitary gland volume development, but there is still a paucity of data in literature about this issue. We should be aware of other cases like this one, and a correct differential diagnosis may contribute to contraindicate transsphenoidal surgery. When a childhood abuse history is present, we recommend admission to a psychiatric facility for adequate treatment.


The surgical outcome and the surgical strategy of percutaneous endoscopic discectomy for recurrent disk herniation.
A retrospective analysis. To present the surgical outcome of percutaneous endoscopic discectomy (PED) for recurrent herniated intervertebral disk disease (HIVD) and to suggest a surgical strategy. Revision discectomy is technically demanding because of the scar tissue, unclear anatomic planes, and retraumatization to the posterior structures. Although open microdiscectomy is a standard method, endoscopic techniques have emerged as a surgical alternative with comparable results. PED was performed with either the transforaminal (PETD) or the interlaminar approach (PEID). Previous reports have shown the surgical outcomes of PETD or PEID for recurrent HIVD, but the application of each approach was not addressed clearly. Consecutive 26 patients (M:F=16:10, mean age 53.1±12.4 y), who underwent PED for recurrent HIVD, were enrolled. The previous operation was an open discectomy in 22, a PETD in 2, and a PEID in 2 patients. PETD was considered preferentially, if it was feasible (n=11), because of the scar tissue formed by the previous operation. PEID was chosen (n=15) because of a high iliac crest (8), high canal compromise (3), high-grade inferior migration (2), and narrow neural foramen (2). All patients were followed up for 19.3±11.3 months. In all patients, the recurrent disk material was removed successfully, and conversion to an open surgery was not necessary. Postoperative magnetic resonance imaging revealed that the ruptured disk was removed successfully in all cases. A favorable outcome (excellent or good outcome by MacNab's criteria) was achieved in 21 patients (81%). Re-recurrence occurred in 2 patients at 6 and 12 months postoperatively. Risk factors for an unfavorable outcome were not found in the present study (P>0.05). The relevant utilization of updated surgical techniques may be helpful in overcoming the difficulty of revision surgery.


Grafting poly(methyl methacrylate) onto polyimide nanofibers via "click" reaction.
Surface modification of azide-decorated polyimide (PI) nanofibers with well-defined alkyne-terminated poly(methyl methacrylate) (PMMA) was accomplished via the combination of atom transfer radical polymerization (ATRP) and "click" chemistry. In this work, PI nanofibers were prepared via electrospun polyamic acid (PAA), followed by thermal imidization. Grafting of PMMA onto PI nanofibers was accomplished in three steps: (1) choloromethylation and azidization of PI nanofibers; (2) preparation of alkyne-terminated PMMA by ATRP of methyl methacrylate in toluene using propargyl 2-bromopropionate as initiator; (3) click coupling between the azidized PI nanofibers and the alkyne-terminated PMMA under the catalysis of Cu(I)Br/N,N,N',N''-pentamethyldiethylenetriamine (PMDETA). Gel permeation chromatography (GPC), (1)H NMR, and Fourier transform infrared (FT-IR) all confirmed the structure of alkyne-terminated poly(methyl methacrylate). The modified surface was characterized by X-ray photoelectron spectroscopy (XPS) after each modification stage. XPS and scanning electron microscope (SEM) were utilized to confirm PMMA-functionalized PI nanofibers, showing polymer coatings present on the surface of PI nanofibers. PI-g-PMMA nanofibers exhibited a more significant reinforcing effect compared to that with ungrafted PI nanofibers.


Removal of Formaldehyde and Its Analogues Using a Hybrid Assembly of Pyrene-Modified Hydrazide and rGO: A Negative Carbon Emission and Green Chemical Decomposition Method.
Indoor gaseous formaldehyde is the main environmental pollutant that can cause fatal threats to human health. A number of physical and chemical methods have been developed to tackle this issue. However, the existing methods are still unsatisfactory to meet the requirement of sustainable development owing to the flaws of low efficiency and reversible or second pollution. Herein, a chemical method based on a nucleophilic reaction between hydrazine and aldehyde that generates the only by-product of H2O is designed for the removal of formaldehyde. 1-Pyrenebutyric hydrazide was synthesized by a simple esterification reaction and then self-assembled on reduced graphene oxide (rGO) with a large surface area by forming π-π stacking to obtain a composite for chemical removal of gaseous formaldehyde under ambient conditions. In a practical test, the formaldehyde removal rate could reach 91% of the theoretical value, which meets the requirement for commercial formaldehyde removal applications. After 10 times recycling, the formaldehyde removal rate still remains as high as 85%. Moreover, the composite could be regenerated in weak acidic media, which greatly reduce the manufacturing cost in practical applications.


Polarons, bipolarons, and side-by-side polarons in reduction of oligofluorenes.
The nature of charge carriers in conjugated polymers was elucidated through optical spectroscopy following single- and multielectron reduction of 2,7-(9,9-dihexylfluorene) oligomers, F(n), n = 1-10, yielding spectra with the two bands typical of polarons upon single reduction. For short oligomers addition of a second electron gave a single band demonstrating the classic polaron-bipolaron transition. However, for long oligomers double reductions yielded spectra with two bands, better described as two polarons, possibly residing side-by-side in the F(n) chains. The singly reduced anions do not appear to delocalize over the entire length of the longer conjugated systems; instead they are polarons occupying approximately four fluorene repeat units. The polarons of F(3) and F(4) display sharp absorption bands, but for longer oligomers the bands broaden, possibly due to fluctuations of the lengths of these unconfined polarons. DFT calculations with long-range-corrected functionals were fully consistent with the experiments describing polarons in anions, bipolarons in dianions of short oligomers, and side-by-side polarons in dianions of long oligomers, while results from standard functionals were not compatible with the experimental results. The computations found F(10)(2-), for example, to be an open-shell singlet (<S(2)> ≈ 1), with electrons in two side-by-side orbitals, while dianions of shorter oligomers experienced a gradual transition to bipolarons with states of intermediate character at intermediate lengths. The energies and extinction coefficients of each anionic species were measured by ultraviolet-visible-near-infrared absorption spectroscopy with chemical reduction and pulse radiolysis. Reduction potentials determined from equilibria mirrored oxidation potentials reported by Chi and Wegner. Anions of oligomers four or more units in length contained vestigial neutral (VN) absorption bands that arise from neutral parts of the chain. Energies of the VN bands correspond to those of oligomers shorter by four units.


Phylogenetic relationships between Drosophila subobscura, D. guanche and D. madeirensis based on Southern analysis of heat shock genes.
A Southern analysis of genomic DNA using Drosophila melanogaster probes for the major heat shock protein genes (Hsp82, Hsp70, Hsps encoding small proteins) was made to study the phylogenetic relationships between three Drosophila species belonging to the obscura group (D. subobscura, D. guanche, and D. madeirensis). The phylogenetic trees showed that D. madeirensis and D. subobscura are the most closely related species in the triad, while D. guanche is the most distantly related one. As in other Drosophila species, Hsp82 is a single copy gene in D. subobscura, D. guanche, and D. madeirensis, while Hsp70 and Hsps, which encode small proteins, are genic families. At least four sequences homologous to D. melanogaster Hsp70 were found in the obscura group species. These species have sequences which showed similarity with the four small Hsps of D. melanogaster.


Defining disability in psychosis: performance of the diagnostic interview for psychosis-disability module (DIP-DIS) in the Australian National Survey of Psychotic Disorders.
We aimed to use data from the Australian Survey of Mental Health and Wellbeing to examine the psychometric properties of the Diagnostic Interview for Psychosis-Disability Module (DIP-DIS). The DIP-DIS is a semi-structured questionnaire specially designed to assess disability associated with psychotic disorders. The psychometric properties of the instrument were determined by examining its inter-rater reliability, internal structure, as well as its criterion and discriminant validities. Analysis shows: (1) that it can be rated reliably by trained interviewers, (2) that the items are complementary but tap a number of different domains, (3) that four factors account for over 66% of the variance, and (4) that it is sensitive to differing clinical populations with expected differences in level of disability. Ratings on the DIP-DIS bore significant relationships with a criterion measure of quality of life. The DIP-DIS has encouraging psychometric properties for cross-sectional assessment of disability and may be useful in future studies of disablement associated with psychosis. Future work should examine its sensitivity to change.


[Polymorphism of DXYS267 locus and application of its Y-specific single nucleotide substitutions].
To investigate the polymorphism of DXYS267 locus in China Han population and find the application and characters of its Y-specific single nucleotide substitutions. The locus was analyzed by PCR and PAGE in silver-staining. The Y-specific STR was amplified with newly designed primers according to the Y-specific single nucleotide substitutions. Six alleles were detected in Han population in Wuhan. Exact tests demonstrated that genotype frequencies did not deviate from Hardy-Weinberg equilibrium. Heterozygosity of DXYS267 was 0.6706, discrimination power (DP) was 0.8433, and the probability of paternity exclusion (PE) was 0.5957. The Y-specific STR of DXYS267 was successfully amplified with the new primer. The 4 alleles for Y-STR were detected with haplotype diversity (HD) 0.6372. The DXYS267 locus is appropriate for individual identification and paternity testing. The new primer is useful for individual and paternity testing involving brothers and mixed stains.


Pacinian Signals Determine the Direction and Magnitude of the Effect of Vibration on Pain.
Although the ability of vibration to reduce pain has been extensively documented, an occasional participant reports that vibration increases pain. For pain patients, such reports may reflect pathophysiology, but this is unlikely in studies of experimental pain in healthy participants. In the present series of experiments on 27 pain-free individuals, we manipulated both the frequency (12, 50, and 80 Hz) and amplitude of vibration to more fully characterize vibratory pain modulation. The noxious stimulus was pressure applied to a finger, and vibration was delivered to the fleshy palmar pad at the base of the same finger. Subjects continuously reported pain on a Visual Analog Scale. Intermittent vibration was used to minimize peripheral vibratory adaptation. Pain records at 12 and 50 Hz were similar; pooling them revealed significant hypoalgesia at the highest amplitude. At 80 Hz, in contrast, the middle amplitude produced hypoalgesia, but a significant shift toward hyperalgesia occurred at the highest amplitude. The strong correlation ( r = .81) between the Pacinian-weighted power of a vibration and the absolute value of the pain modulation it produces indicates that the Pacinian system plays a key role in vibratory hypoalgesia or hyperalgesia.


Assessment of organizational capacity for evidence-based health systems operations in Nigeria.
In Nigeria, health outcomes are unacceptably low largely due to the inability of the health system to function optimally. As part of a strategy to strengthen the health system, an assessment of institutional capacity for use of evidence for health system operations was conducted. The health system operations in terms of stewardship, health administration, service delivery, and access to essential medical products/technologies were fairly adequate. In terms of generation/strategic use of information, health financing, and health workforce, the operations were generally inadequate. There is need to evolve strategies that will guarantee equitable and sustained improvements across health services and health outcomes.


Treatment of hypercholesterolemia in black patients.
The treatment of hypercholesterolemia in the black patient will be the next public health challenge facing physicians in the black community. Cost-effective care of hypercholesterolemia will be necessary and is possible, but it will require skill in the use of available therapies, extensive patient education, and excellent communication between patients and health care providers.


A new species of Nemoura Latreille (Plecoptera: Nemouridae) from Amur River Basin (South of the Russian Far East).
Nemoura sirotskii sp. n. (Plecoptera, Nemouridae) is described as a new stonefly species from the tributary streams of Zeya Reservoir (Amur River Basin) in the south of the Russian Far East. Detailed descriptions and illustrations are provided for the larvae and adult specimens. The diagnostic characters distinguishing it from sympatric species N. arctica are discussed.


Effects of the new ethacrynic acid derivative SA9000 on intraocular pressure in cats and monkeys.
To evaluate the pharmacological characteristics of the new ethacrynic acid (ECA) derivative SA9000, we examined its ocular hypotensive effects in cats and cynomolgus monkeys, its corneal toxicity in rabbits, and its binding affinities for forty-three receptors, ion channels, and second messenger systems. A 20 microl injection into the anterior chamber of eye (intracameral injection) of 0.1 mM SA9000 significantly reduced intraocular pressure (IOP) 3.8 mmHg in cats. A 10 microl intracameral injection of 1 mM SA9000 significantly reduced IOP 7 mmHg in living monkeys without evidence of in vivo (or in vitro) toxicity. The ocular hypotensive effect of SA9000 in monkeys was greater than that of ECA. The morphology of corneal endothelial and epithelial cells in rabbit eyes after intracameral injection of SA9000 was observed using electron microphotography. SA9000 at 2 mM did not induce any abnormalities, indicating that it has no corneal toxicity at a concentration higher than the minimum needed for an ocular hypotensive effect (1 mM). SA9000 at 0.01 mM showed negligible binding affinity for, or inhibition of, forty-three different receptors, ion channel proteins, and second messenger systems. These findings indicate that SA9000 has the potential to be both effective and safe as an ocular hypotensive drug, although the mechanism of action remains unclear.