Differential gene expression in a tripartite interaction: Drosophila, Spiroplasma and parasitic wasps.
Several facultative bacterial symbionts of insects protect their hosts against natural enemies. Spiroplasma poulsonii strain sMel (hereafter Spiroplasma), a male-killing heritable symbiont of Drosophila melanogaster, confers protection against some species of parasitic wasps. Several lines of evidence suggest that Spiroplasma-encoded ribosome inactivating proteins (RIPs) are involved in the protection mechanism, but the potential contribution of the fly-encoded functions (e.g., immune response), has not been deeply explored. Here we used RNA-seq to evaluate the response of D. melanogaster to infection by Spiroplasma and parasitism by the Spiroplasma-susceptible wasp Leptopilina heterotoma, and the Spiroplasma-resistant wasp Ganaspis sp. In addition, we used quantitative (q)PCR to evaluate the transcript levels of the Spiroplasma-encoded Ribosomal inactivation protein (RIP) genes. In the absence of Spiroplasma infection, we found evidence of Drosophila immune activation by Ganaspis sp., but not by L. heterotoma, which in turn negatively influenced functions associated with male gonad development. As expected for a symbiont that kills males, we detected extensive downregulation in the Spiroplasma-infected treatments of genes known to have male-biased expression. We detected very few genes whose expression patterns appeared to be influenced by the Spiroplasma-L. heterotoma interaction, and these genes are not known to be associated with immune response. For most of these genes, parasitism by L. heterotoma (in the absence of Spiroplasma) caused an expression change that was at least partly reversed when both L. heterotoma and Spiroplasma were present. It is unclear whether such genes are involved in the Spiroplasma-mediated mechanism that leads to wasp death and/or fly rescue. Nonetheless, the expression pattern of some of these genes, which reportedly undergo expression shifts during the larva-to-pupa transition, is suggestive of an influence of Spiroplasma on the development time of L. heterotoma-parasitized flies. One of the five RIP genes (RIP2) was consistently highly expressed independently of wasp parasitism, in two substrains of sMel. Finally, the RNAseq data revealed evidence consistent with RIP-induced damage in the ribosomal (r)RNA of the Spiroplasma-susceptible, but not the Spiroplasma-resistant, wasp. Acknowledging the caveat that we lacked adequate power to detect the majority of DE genes with fold-changes lower than 3, we conclude that immune priming is unlikely to contribute to the Spiroplasma-mediated protection against wasps, and that the mechanism by which Ganaspis sp. resists/tolerates Spiroplasma does not involve inhibition of RIP transcription.


Excretion of artifactual endogenous digitalis-like factors.
Radioimmunoassays have been used to detect digoxin-like immunoreactive factors (DLF) in the plasma and urine of hypertensive patients and rats with deoxycorticosterone acetate (DOCA)-salt hypertension. Uninephrectomized rats (n = 9), given 15 mg DOCA . kg-1 . wk-1, were fed a standard rat chow supplemented with 2% NaCl (DOCA-HS); control animals (n = 15) were given vehicle injection and a specially formulated low-salt diet (0.05% NaCl). At 4 wk, DOCA-HS rats were hypertensive (121.4 +/- 10.1 vs. 88 +/- 4.4 Torr, mean +/- SEM, P less than 0.05) and excreted more DLF (2.7 +/- 1.1 vs. 0.2 +/- 0.1 ng digoxin equivalents . day-1, P less than 0.001) compared with control rats. DLF, partially purified from DOCA-HS urine by antidigoxin antibody immunoaffinity chromatography, was found to have a molecular weight less than 2,000, was resistant to acid hydrolysis or proteases, and had many properties of the cardiac glycosides, including inhibition of Na+-K+-ATPase activity, displacement of ouabain from human erythrocyte membranes, and inhibition of 86Rb influx into red blood cells. When DOCA-HS rats were switched to the low-sodium chow, DLF excretion dropped precipitously. No measurable DLF (less than 10 pg/ml) was detected in the plasma of rats eating either chow. However, greater than 95% of the urinary DLF could be attributed to a contaminant in the standard laboratory chow; rats fed the low-salt chow supplemented with 2% NaCl excreted much less DLF, and DLF was isolated from the standard chow.(ABSTRACT TRUNCATED AT 250 WORDS)


Reliability of ion accumulation and growth components for selecting salt tolerant lines in large populations of rice.
Ion accumulation and growth under salt stress was studied in two experiments in a rice mapping population derived from parents CO39 and Moroberekan with 4-fold differences in shoot Na+ accumulation. The 120 recombinant inbred lines (RILs) had differences up to 100-fold in Na+. Measurement of 'salt tolerance' (biomass production of the RILs in 100mM NaCl relative to controls) after 42 days showed a 2-fold variation in 'salt tolerance' between parents, with five RILs being more tolerant than the more tolerant parent CO39. The reliability of various traits for selecting salt tolerance in large populations was explored by measuring Na+, K+ and K+/Na+ ratios in leaf blades and sheaths after 7 or 21 days of exposure to 100mM NaCl, and their correlation with various growth components and with leaf injury. The highest correlations were found for Na+ in the leaf blade on day 21 with injury at day 42 in both experiments (r=0.7). Earlier measurements of Na+ or of injury had lower correlations. The most sensitive growth components were tiller number plant-1 and shoot water content (g water g-1 dry weight), and these were correlated significantly with Na+ and, to a lesser extent, with K+/Na+. These studies showed that exposure for at least 42 days may be needed to clearly demonstrate the beneficial effect of the trait for Na+ exclusion on growth under salinity.


Fine needle aspiration cytology of cat scratch disease.
The cytologic features of cat scratch disease diagnosed by fine needle aspiration cytology of a right inguinal lymph node in a 23-year-old woman are reported. Characteristic granulomas, with peripherally palisading epithelioid histiocytes and centrally located neutrophils, and an associated polymorphic cell population were observed. The cytologic pattern closely parallels the expected histopathologic findings and therefore can suggest the diagnosis in unsuspected cases or can confirm the clinical impression. The cytologic differential diagnosis and a discussion of other granulomatous lymphadenitis are presented.


Salivary cortisol levels are associated with outcomes of weight reduction therapy in obese Japanese patients.
Dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis can increase the risk of cardiovascular disease (CVD). However, the detailed relationships of HPA axis activity with weight reduction and CVD risk factors in obese patients have not been examined. This study was designed to elucidate the associations of salivary cortisol levels with weight reduction and CVD risk factors in obese patients. As a marker of HPA axis activity, we measured the morning salivary cortisol levels of 83 obese Japanese outpatients. We also examined metabolic parameters, inflammatory markers, and indicators of arterial stiffness, that is, the pulse wave velocity and cardio-ankle vascular index. All 83 obese patients underwent 3-month weight reduction therapy with lifestyle modification. At the baseline, multivariate regression analysis revealed that only logarithmic transformation of C-reactive protein (β = 0.258, P < .05) and cardio-ankle vascular index (β = 0.233, P < .05) were independent determinants of the salivary cortisol levels. However, other metabolic parameters were not significantly associated with the salivary cortisol levels. In addition, lower salivary cortisol levels and higher body weight at the baseline were the only independent determinants of successful weight loss through the weight reduction therapy (P < .01). The present study demonstrates that the baseline morning salivary cortisol levels are significantly associated with the levels of an inflammatory marker, arterial stiffness, and successful weight reduction in obese patients. Therefore, salivary cortisol could be a useful marker for assessing and managing body weight and CVD risk factors in obese patients.


Depressive symptom clusters are differentially associated with atherosclerotic disease.
Depression increases the risk of subsequent vascular events in both cardiac and non-cardiac patients. Atherosclerosis, the underlying process leading to vascular events, has been associated with depression. This association, however, may be confounded by the somatic-affective symptoms being a consequence of cardiovascular disease. While taking into account the differentiation between somatic-affective and cognitive-affective symptoms of depression, we examined the association between depression and atherosclerosis in a community-based sample. In 1261 participants of the Nijmegen Biomedical Study (NBS), aged 50-70 years and free of stroke and dementia, we measured the intima-media thickness (IMT) of the carotid artery as a measure of atherosclerosis and we assessed depressive symptoms using the Beck Depression Inventory (BDI). Principal components analysis (PCA) of the BDI items yielded two factors, representing a cognitive-affective and a somatic-affective symptom cluster. While correcting for confounders, we used separate multiple regression analyses to test the BDI sum score and both depression symptom clusters. We found a significant correlation between the BDI sum score and the IMT. Cognitive-affective, but not somatic-affective, symptoms were also associated with the IMT. When we stratified for coronary artery disease (CAD), the somatic-affective symptom cluster correlated significantly with depression in both patients with and patients without CAD. The association between depressive symptoms and atherosclerosis is explained by the somatic-affective symptom cluster of depression. Subclinical vascular disease thus may inflate depressive symptom scores and may explain why treatment of depression in cardiac patients hardly affects vascular outcome.


Renal sugar transport in the winter flounder. VI. Reabsorption of D-mannose.
The transport of D-mannose (Man) in flounder kidney was studied using renal clearance techniques in vivo and brush border membrane (BBM) vesicles in vitro. At plasma concentrations of 50-100 microM Man, the winter flounder (Pseudopleuronectes americanus) reabsorbed up to 70% of the filtered sugar. Man phosphates, but not free Man, accumulated in renal cells. Reabsorption of Man was reduced by phlorizin, D-glucose, methyl-alpha-D-glucoside, methyl-alpha-D-mannoside, and 2-deoxy-D-glucose. In BBM vesicles a Na+-dependent, phlorizin-sensitive overshoot in Man uptake (10 microM) was seen. Na+-dependent Man uptake was saturable, with an apparent Km of 127 microM. The transport properties for Man were identical in BBM vesicles from the winter flounder and southern flounder (Paralichthys lethostigma). The transport specificity was determined by cis-inhibition and trans-stimulation experiments with BBM. Glucose, galactose, 1,5-anhydro-D-mannitol (i.e., 1-deoxymannose), 2-deoxy-2-fluoro-D-glucose, and methyl-alpha-mannoside were shown to share the carrier-mediating mannose transport. 2-Deoxyglucose, methyl-alpha-2-deoxy-D-glucoside, and both the isomers (alpha and beta) of methyl-D-glucoside did not. In contrast, alpha-methyl-D-glucoside inhibited D-glucose transport both in vivo and in BBM vesicles. It is concluded that Man reabsorption in the flounder occurs via a Na+-cotransport system that also handles glucose but that differs from the glucose/methyl-alpha-D-glucoside reabsorptive pathway in that 1) an oxygen on C-1 is not required, and 2) an axial configuration for -OH on C-2 (C1 conformation) is readily accommodated.


Immunodiffusion analyses of Mycobacterium farcinogenes, Mycobacterium senegalense and some other mycobacteria.
Thirty-one strains of Mycobacterium farcinogenes and M. senegalense were analysed together with twenty-five strains representing ten mycobacterial species. The comparative immunodiffusion technique was employed, using two reference systems, one for M. farcinogenes and the other for M. senegalense. The results indicate that the slow growing M. farcinogenes and the fast growing M. senegalense strains are closely related and can not be separated into two clearly distinct clusters. Both species were closely related to M. fortuitum, including strains designated 'M. peregrinum', but clearly different from other tested mycobacterial species. The serological data are consistent with the classification of M. farcinogenes and M. senegalense, and possibly M. fortuitum, in a single species. The results are discussed within the context of other taxonomic analyses of M. farcinogenes and M. senegalense.


User Centered Design of Interaction Techniques for VR-Based Automotive Design Reviews.
The exterior design is one of the most important selling propositions in the automotive premium market. Because of progressing digitization in the automotive industry, it is increasingly assessed using virtual 3D models. In this context, Virtual Reality (VR) is a key technology of continuously growing importance. However, complicated interaction in VR proves to be a major drawback in industrial settings. In this paper, we report insights of our user centered approach aiming at appropriate VR interaction techniques supporting designers, engineers, and management executives optimally in design assessment. Our approach splits into two iterations according to the main interaction tasks Visual Inspection and Model Comparison. In each iteration, alternative interaction techniques were conceptualized, implemented as prototypes, and evaluated in a user study in terms of Usability, User Experience, Intuitiveness and Task Load. In the first iteration six interaction techniques for Visual Inspection, two speech-based, two gesture-based, and two touch-based variants, were studied. Incorporating the results, the second iteration explores three interaction techniques for Model Comparison utilizing (1) a portable touch remote, (2) hand and body gestures, and (3) a multimodal mix of both. The final concepts yielded high ratings by the participants, but showed significant differences between rational and emotional aspects. We conclude that the acceptance of VR in automotive design could be facilitated by refining and applying these interaction techniques.


Use and outcomes of venous thromboembolism prophylaxis after spinal fusion surgery.
The number of spinal fusion operations in the USA is rapidly rising, but little is known about optimal venous thromboembolism prophylaxis after spinal surgery. To examine the use of and outcomes associated with venous thromboembolism prophylaxis after spinal fusion surgery in a cohort of 244 US hospitals. We identified all patients with a principal procedure code for spinal fusion surgery in hospitals participating in the Premier Perspective database from 2003 to 2005, and searched for receipt of pharmacologic prophylaxis (subcutaneous unfractionated heparin, low molecular weight heparin, or fondaparinux) and/or mechanical prophylaxis (compression devices and elastic stockings) within the first 7 days after surgery. We also searched for discharge diagnosis codes for venous thromboembolism and postoperative hemorrhage during the index hospitalization and within 30 days after surgery. Among 80,183 spinal fusions performed during the time period, cervical fusions were the most common (49.0%), followed by lumbar fusions (47.8%). Thromboembolism prophylaxis was administered to 60.6% of patients within the first week postoperatively, with the most frequent form being mechanical prophylaxis alone (47.6%). Of the 244 hospitals, 26.2% provided prophylaxis to ≥ 90% of their patients undergoing spinal fusion; however, 33.2% provided prophylaxis to fewer than 50% of their patients. The rate of diagnosed venous thromboembolism within 30 days after surgery was 0.45%, and the rate of postoperative hemorrhage was 1.1%. Substantial variation exists in the use of thromboembolism prophylaxis after spinal fusion surgery in the USA. Nevertheless, overall rates of diagnosed thromboembolism after spinal fusion appear to be low.


[Toxic effect of phosphamide after simultaneous entrance into the body through the gastrointestinal tract and respiratory organs].
The experiment involved an investigation into the action of O,O-dimethyl-S-(N-methyl-carbomoilmethyl)-dithiophosphate (phosphamide), used at the level of the liminal dose (4 mg/kg) and in a concentration of 1.9 mg/m3, as compared with the effect of 1/2 of the liminal dose and 1/2 of the thereshold concentration. Both were simultaneously introduced into the organism of test albino rats for a period of 4 months and their complex action showed an intensification of the toxic effect. In evidence was also a more marked anticholinesterase action, a higher level of the insecticide in biological substrates and greater changes of hematological indices.


[Problems of geriatric patients with managing drug containers].
The purpose of the study was to measure the prevalence of difficulties in elderly inpatients in opening a range of common commercial drug packagings, in breaking a bar-scored tablet, and in reading medication instructions. Sixty-seven patients (female: 47; male: 20, mean age: 81.6 +/- 6.1) who reported that they had managed their medication independently before hospital admission, underwent a comprehensive geriatric assessment. They were also asked to remove tablets and drops from various commercial drug packagings and a "dosett", to break a tablet, and to read medication instructions enclosed in the packings. Only 21 patients (31%) were able to perform all tasks. Thirty-one patients (46.3%) failed in opening the "push and turn" bottle and 44 patients (65.7%) were unable to open the flip-top container. There were significant differences (p < 0.05) in age, cognitive capacity, handgrip, and manual dexterity between the patients who were able to perform all tasks, and those who were not able to do so. Many of the common medication packagings impede a reliable management of drugs by elderly patients.


Plasma Cell-Free Mitochondrial DNA as a Marker of Geriatric Syndromes in Older Adults With HIV.
Older people with HIV experience more comorbidities and geriatric syndromes than their HIV-negative peers, perhaps due to residual inflammation despite suppressive antiretroviral therapy. Cell-free mitochondrial DNA (cfmtDNA) released during necrosis-mediated cell death potentially acts as both mediator and marker of inflammatory dysregulation. Thus, we evaluated plasma cfmtDNA as a potential biomarker of geriatric syndromes. Participants underwent the Montreal Cognitive Assessment (MoCA), frailty testing, and measurement of plasma cfmtDNA by qPCR and inflammatory markers including C-reactive protein, interleukin-6 (IL-6), interferon gamma, and tumor necrosis factor alpha in this cross-sectional study. Across 155 participants, the median age was 60 years (Q1, Q3: 56, 64), one-third were female, and 92% had HIV-1 viral load <200 copies/mL. The median MoCA score was 24 (21, 27). The plasma cfmtDNA level was higher in those with cognitive impairment (MoCA <23) ( P = 0.02 by the t test) and remained significantly associated with cognitive impairment in a multivariable logistic regression model controlling for age, sex, race, CD4 T-cell nadir, HIV-1 viremia, and depression. Two-thirds of participants met the criteria for a prefrail or frail state; higher plasma cfmtDNA was associated with slow walk and exhaustion but not overall frailty state. Cognitive dysfunction was not associated with C-reactive protein, IL-6, interferon gamma, or tumor necrosis factor alpha, and frailty state was only associated with IL-6. Plasma cfmtDNA may have a role as a novel biomarker of cognitive dysfunction and key components of frailty. Longitudinal investigation of cfmtDNA is warranted to assess its utility as a biomarker of geriatric syndromes in older people with HIV.


Robo1 regulates the migration and laminar distribution of upper-layer pyramidal neurons of the cerebral cortex.
Laminar organization is a key feature of the mammalian cerebral cortex, but the mechanisms by which final positioning and "inside-out" distribution of neurons are determined remain largely unknown. Here, we demonstrate that Robo1, a member of the family of Roundabout receptors, regulates the correct positioning of layers II/III pyramidal neurons in the neocortex. Specifically, we used RNA interference in mice to suppress the expression of Robo1 in a subset of layers II/III neurons, and observed the positions of these cells at distinct developmental stages. In contrast to control neurons that migrated toward the pial surface by P1, Robo1-suppressed neurons exhibited a delay in entering the cortical plate at respective stages. Unexpectedly, after the first postnatal week, these neurons were predominantly located in the upper part of layers II/III, in contrast to control cells that were distributed throughout these layers. Sequential electroporation studies revealed that Robo1-suppressed cells failed to establish the characteristic inside-out neuronal distribution and, instead, they accumulated beneath the marginal zone regardless of their birthdate. These results demonstrate that Robo receptors play a crucial role in neocortical lamination and particularly in the positioning of layers II/III pyramidal neurons.


Long-term benefits of omalizumab in a patient with severe non-allergic asthma.
Currently, omalizumab is indicated for the treatment of patients with severe allergic uncontrolled asthma despite optimal therapy. We studied a 52-year-old man who has been suffering from severe non allergic steroid-resistant asthma with increased levels of total IgE and a lot of comorbidity. After a 3 years long treatment with omalizumab, he presented a significant improvement in disease control in terms of hospitalizations, exacerbation, quality of life and lung function with good safety profile. Our case shows, after a long follow-up, how omalizumab can be effective in a severe form of non-atopic asthma. It is therefore hoped that further studies can identify indicators that are able to give to clinicians information about patients who can be responsive to monoclonal anti-IgE antibody even if non allergic.


Predicting the development of hemophilic arthropathy in patients with hemophilia based on patient age: a retrospective single-center database study.
Patients with hemophilia (PWH) develop hemophilic arthropathy of the major joints due to recurrent hemarthrosis. This study retrospectively estimated the age at which PWH may expect to develop hemophilic arthropathy and undergo joint replacement surgery. Using retrospective data from PWH at a Czech orthopedic center, Kaplan Meier analyses were used to estimate the cumulative proportions of patients with hemophilic arthropathy and undergoing joint replacement surgery as a function of age. Based on 1028 joint examinations in 167 PWH, hemophilic arthropathy of the knees, elbows, ankles and hips was estimated to develop by a median age of 48, 51, 52 and 61 years, respectively, with ≈80% of patients having such damage by ≈70 years of age. Hemophilic arthropathy of the shoulder occurred much later (median >80 years). In patients undergoing knee or hip replacement surgery, hemophilic arthropathy of the knee and hip occurred at a median age of ≈50 and ≈60 years, respectively, with replacement surgery occurring at a median of ≈70 and >75 years. In PWH, the risk of developing hemophilic arthropathy accumulates continuously over the patient's lifetime, allowing predictions about the ages at which such damage and joint replacement surgery may occur.


[Effect of encephalectomy on the corticosterone content of rat fetal adrenals].
Changes in the functional state of the hypophysial-adrenal system after the removal of the hypothalamus (encephalectomy in utero) were studied in rat fetuses. The hormonal activity of the adrenal glands was evaluated by the direct fluorimetric determination of corticosterone in this organ. Removal of the hypothalamus in 18.5--19.5-day fetuses brought about a significant decrease of corticosterone in the adrenal glands. Injection of the hypothalamus homogenate to fetuses immediately after the encephalectomy prevented this decrease. The results obtained supported the existence of functional relationship between the hypothalamus and the hypophysial-adrenal system in rat fetuses.


Studies on anabolic steroids. The mass spectra of 17 alpha-methyl-17 beta-hydroxy-1,4-androstadien-3-one (Dianabol) and its metabolites.
The metabolism of 17 alpha-methyl-17 beta-hydroxy-1,4-androstadien-3-one (dianabol) in human adults has been studied in detail by computer aided capillary gas chromatography mass spectrometry. After oral administration to man six metabolites were determined in the free fraction of the urine samples, the structures of which have been identified as 17-epidianabol, three isomers of 6-hydroxydianabol, 17 alpha-methyl-17 beta-hydroxy-1,4,6-androstatrien-3-one (delta 6-dianabol) and 18-nor-17,17-dimethyl-1,4,13(14)-androstatrien-3-one, respectively. In agreement with previous observations no measurable amounts of the administered drug itself could be detected in any of the urine samples investigated. The mass spectra of all metabolites and the main fragmentation processes are discussed in detail.


Health care reform in Oregon.
Oregon has led the United States in asking the difficult questions regarding what constitutes basic health care benefits. Oregon's experience in attempting to answer the question "what are basic health care benefits?" offers some learning opportunities for Canada in the face of diminishing financial resources and health care reform.


Effects of cations, phospholipases, and neuraminidase on calcium binding to "gas-dissected" membranes from cultured cardiac cells.
Sarcolemmal membranes prepared by "gas dissection" from monolayers of cultured neonatal rat heart cells were studied with respect to their ability to bind calcium. Lanthanum displacement of calcium was 168 +/- 7 nmol/mg sarcolammel protein. This represents 3.21 mmol Ca/kg dry weight original cells on the basis of the measured membrane protein: dry cell weight ratio of 19.1 g/kg. Lanthanum-displaceable calcium from whole cells was essentially equal (3.32 mmol/kg dry weight), which indicates that all calcium displaceable from whole cells by lanthanum is localized to sarcolemmal sites. The potency of a series of divalent cations for calcium displacement from the sarcolemma was according to similarity of their crystal radii to that of calcium (cadmium greater than manganese greater than magnesium). This order was the same for the cations' ability to displace calcium from whole cells and for their ability to uncouple excitation from contraction in neonatal papillary muscle. The membranes were treated with four enzymes: phospholipase A2, phospholipase C, phopholipase D, and neuraminidase. Phospholipase A2 and phospholipase D produced significantly increased calcium-binding. The increased binding secondary to phospholipase A2 treatment was eliminated by an albumin wash which was indicative of binding to the fatty acid product of hydrolysis. The increase after phospholipase D treatment can be attributed to an increase in phosphatidate, with attendant increase in net anionic charge on the membrane.(ABSTRACT TRUNCATED AT 250 WORDS)


Coupled electromagnetic-thermodynamic simulations of microwave heating problems using the FDTD algorithm.
A practical implementation of a hybrid simulation system capable of modeling coupled electromagnetic-thermodynamic problems typical in microwave heating is described. The paper presents two approaches to modeling such problems. Both are based on an FDTD-based commercial electromagnetic solver coupled to an external thermodynamic analysis tool required for calculations of heat diffusion. The first approach utilizes a simple FDTD-based thermal solver while in the second it is replaced by a universal commercial CFD solver. The accuracy of the two modeling systems is verified against the original experimental data as well as the measurement results available in literature.


Deleterious Germline Mutations in Patients With Apparently Sporadic Pancreatic Adenocarcinoma.
Purpose Deleterious germline mutations contribute to pancreatic cancer susceptibility and are well documented in families in which multiple members have had pancreatic cancer. Methods To define the prevalence of these germline mutations in patients with apparently sporadic pancreatic cancer, we sequenced 32 genes, including known pancreatic cancer susceptibility genes, in DNA prepared from normal tissue obtained from 854 patients with pancreatic ductal adenocarcinoma, 288 patients with other pancreatic and periampullary neoplasms, and 51 patients with non-neoplastic diseases who underwent pancreatic resection at Johns Hopkins Hospital between 2000 and 2015. Results Thirty-three (3.9%; 95% CI, 3.0% to 5.8%) of 854 patients with pancreatic cancer had a deleterious germline mutation, 31 (3.5%) of which affected known familial pancreatic cancer susceptibility genes: BRCA2 (12 patients), ATM (10 patients), BRCA1 (3 patients), PALB2 (2 patients), MLH1 (2 patients), CDKN2A (1 patient), and TP53 (1 patient). Patients with these germline mutations were younger than those without (mean ± SD, 60.8 ± 10.6 v 65.1 ± 10.5 years; P = .03). Deleterious germline mutations were also found in BUB1B (1) and BUB3 (1). Only three of these 33 patients had reported a family history of pancreatic cancer, and most did not have a cancer family history to suggest an inherited cancer syndrome. Five (1.7%) of 288 patients with other periampullary neoplasms also had a deleterious germline mutation. Conclusion Germline mutations in pancreatic cancer susceptibility genes are commonly identified in patients with pancreatic cancer without a significant family history of cancer. These deleterious pancreatic cancer susceptibility gene mutations, some of which are therapeutically targetable, will be missed if current family history guidelines are the main criteria used to determine the appropriateness of gene testing.


Electromagnetic stimulation of bone repair: a histomorphometric study.
The effect of pulsing electromagnetic fields (PEMFs) on bone repair was studied in principal metacarpal bones of eight adult male horses: Six horses were treated with PEMFs, and two horses were untreated. In treated horses, Helmholtz coils were applied during a 60-day period to the left metacarpal bones, bored with eight holes of equal diameter and depth, from the middiaphysis toward the distal metaphysis. Eight equal holes bored in the right metacarpal, surrounded by unactivated Helmholtz coils, were taken as controls. The two untreated horses were taken as additional control. The results of computer-assisted histomorphometric analysis indicate that (a) in diaphyseal levels, the amount of bone formed during 60 days is significantly greater (p less than 0.01) in PEMF-treated holes than in contralateral ones and those in control horses; (b) in metaphyseal levels, PEMF-treated holes are sometimes more closed, sometimes less, as compared with contralateral holes and those in control horses; in any case the statistical analysis indicates that the symmetry in the rate of hole repair, found between the two antimeres of control horses, is not appreciable at metaphyseal levels also; (c) there was no statistically significant difference between untreated holes in PEMF-treated horses and holes in control horses, neither at diaphyseal nor at metaphyseal levels. These preliminary findings indicate that PEMFs at low frequency influence the process of bone repair on both diaphysis and metaphysis, and seem to improve the process of bone repair in skeletal regions normally having a lower osteogenetic activity, i.e., in diaphyses as against metaphyses.


Concordance of Patient and Caregiver Reports on the Quality of Colorectal Cancer Care.
We aimed to better understand how similarly patients with colorectal cancer and caregivers view care quality and to assess factors that may influence concordance. We conducted a secondary analysis of paired patient and caregiver quality ratings of colorectal cancer care in three specific domains: surgery, chemotherapy overall, and chemotherapy nursing. Agreement was assessed with difference scores, concordance with Gwet second-order agreement statistics (AC2), and variation in agreement with stratified analyses. We examined whether the care experiences of patients and caregivers were associated with top-box (most-positive) ratings and examined variations in concordance on the basis of the presence of a top-box score. Four hundred seventeen patient-caregiver dyads completed the surveys. Quality-of-care ratings were positively skewed, with most dyads indicating top-box ratings. Patient and caregiver care experiences were highly associated with top-box ratings. Overall patient-caregiver concordance was very high for all three care domains (surgery: AC2, 0.87 [95% CI, 0.83 to 0.90]; chemotherapy overall: AC2, 0.84 [95% CI, 0.79 to 0.88]; chemotherapy nursing: AC2, 0.91 [95% CI, 0.87 to 0.94]). Stratified analyses of patient and caregiver characteristics did not identify any patterns that consistently affected concordance. The concordance statistic significantly decreased for all three outcomes (P < .001), however, when the patient or caregiver assessed quality as anything other than top box. Caregiver and patient reports on care quality were highly concordant for top-box care and did not vary with patient or caregiver factors. Additional exploration is needed to identify reasons for increased variability when the quality scores were less than a top-box response.


Hydrocephalus in infancy and childhood.
Hydrocephalus is marked by the excessive accumulation of cerebrospinal fluid within the ventricles. The disorder is characterized by an imbalance in the production and reabsorption of cerebrospinal fluid. Congenital hydrocephalus is usually the result of an intrauterine infection or maldevelopment of the aqueduct of Sylvius. Acquired hydrocephalus can be caused by infection, neoplasm or hemorrhage. In infants, hydrocephalus usually presents as progressive head enlargement. The presenting symptoms in children are irritability, headache, nausea, vomiting and lethargy. Diagnosis is made with ultrasonography, computed tomography or magnetic resonance imaging. The majority of patients are treated with cerebrospinal fluid shunt procedures, most commonly the placement of ventriculoperitoneal or lumboperitoneal shunts. The outcome of hydrocephalus is determined by the etiology, the presence or absence of associated anomalies, and the timeliness of diagnosis and treatment.


Cryptococcosis in human immunodeficiency virus-infected children.
Cryptococcosis is a common opportunistic infection in adults with AIDS. Few cases of cryptococcosis complicating pediatric AIDS have been reported. To our knowledge there are no studies that describe the epidemiology, clinical manifestations and outcome of cryptococcosis in a large population of HIV-infected children. We identified the cases of cryptococcosis through a retrospective review of the hospital records of the 473 HIV-infected children prospectively monitored in the Pediatric Branch of the National Cancer Institute during the 8 years from 1987 to 1995. Four (0.85%) patients developed cryptococcosis during the study period. All patients had profound depression of the absolute CD4 counts, a history of previous opportunistic infections, and onset of cryptococcosis in the second decade of life. Cryptococcosis developed as a disseminated infection or a localized process of the lungs. Intermittent fever was the most common presenting manifestation. Serum cryptococcal antigen was positive in all patients and gradually declined after the institution of the antifungal therapy. All patients were treated with amphotericin B with or without flucytosine as initial therapy. Suppressive therapy consisted of fluconazole with or without flucytosine. There were no deaths due to Cryptococcus neoformans. Cryptococcosis is an infrequent yet treatable opportunistic infection of advanced pediatric AIDS that may present with subtle manifestations and warrants careful consideration in the evaluation of febrile HIV-infected children.


[Diet of six-year-old Icelandic children - National dietary survey 2011-2012].
Knowledge of dietary habits makes the basis for public nutrition policy. The aim of this study was to assess dietary intake of Icelandic six-year-olds. Subjects were randomly selected six-year-old children (n=162). Dietary intake was assessed by three-day-weighed food records. Food and nutrient intake was compared with the Icelandic food based dietary guidelines (FBDG) and recommended intake of vitamins and minerals. Fruit and vegetable intake was on average 275±164 g/d, and less than 20% of the subjects consumed ≥400 g/day. Fish and cod liver oil intake was in line with the FBDG among approximately 25% of subjects. Most subjects (87%) consumed at least two portions of dairy products daily. Food with relatively low nutrient density (cakes, cookies, sugar sweetened drinks, sweets and ice-cream) provided up to 25% of total energy intake. The contribution of saturated fatty acids to total energy intake was 14.1%. Less than 20% of the children consumed dietary fibers in line with recommendations, and for saturated fat and salt only 5% consumed less than the recommended upper limits. Average intake of most vitamins and minerals, apart from vitamin-D, was higher than the recommended intake. Although the vitamin and mineral density of the diet seems adequate, with the exception of vitamin-D, the contribution of low energy density food to total energy intake is high. Intake of vegetables, fruits, fish and cod liver oil is not in line with public recommendations. Strategies aiming at improving diet of young children are needed.


Antifungal Activity of Essential Oil of Eucalyptus camaldulensis Dehnh. against Selected Fusarium spp.
The objective of this study was to evaluate the antifungal activity of essential oil (EO) of Eucalyptus camaldulensis Dehnh. against five Fusarium spp. commonly associated with maize. The essential oil had been extracted by steam distillation in a modified Clevenger-type apparatus from leaves of E. camaldulensis and their chemical composition characterized by gas chromatography mass spectrometry. Poisoned food technique was used to determine the percentage inhibition of mycelial growth, minimum inhibitory concentration, and minimum fungicidal concentration of the EO on the test pathogens. Antifungal activity of different concentrations of the EO was evaluated using disc diffusion method. The most abundant compounds identified in the EO were 1,8-cineole (16.2%), α-pinene (15.6%), α-phellandrene (10.0%), and p-cymene (8.1%). The EO produced complete mycelial growth inhibition in all the test pathogens at a concentration of 7-8 μL/mL after five days of incubation. The minimum inhibitory concentration and minimum fungicidal concentration of the EO on the test fungi were in the range of 7-8 μL/mL and 8-10 μL/mL, respectively. These findings confirm the fungicidal properties of E. camaldulensis essential oils and their potential use in the management of economically important Fusarium spp. and as possible alternatives to synthetic fungicides.


Optimal breast cancer screening strategies for older women: current perspectives.
Breast cancer is a major cause of cancer-related deaths among older women, aged 65 years or older. Screening mammography has been shown to be effective in reducing breast cancer mortality in women aged 50-74 years but not among those aged 75 years or older. Given the large heterogeneity in comorbidity status and life expectancy among older women, controversy remains over screening mammography in this population. Diminished life expectancy with aging may decrease the potential screening benefit and increase the risk of harms. In this review, we summarize the evidence on screening mammography utilization, performance, and outcomes and highlight evidence gaps. Optimizing the screening strategy will involve separating older women who will benefit from screening from those who will not benefit by using information on comorbidity status and life expectancy. This review has identified areas related to screening mammography in older women that warrant additional research, including the need to evaluate emerging screening technologies, such as tomosynthesis among older women and precision cancer screening. In the absence of randomized controlled trials, the benefits and harms of continued screening mammography in older women need to be estimated using both population-based cohort data and simulation models.


Neuroborreliosis during natalizumab treatment in multiple sclerosis.
We present a case of acute neuroborreliosis in the setting of long-term treatment with natalizumab. A 33-year-old man was diagnosed with relapsing-remitting multiple sclerosis (MS) in 1999. Following failure of various immunomodulatory treatments including interferon and immunoglobulin, he was treated with mitoxantrone from May 2000 to August 2004. Due to persistently high disease activity, he was also treated with cyclophosphamide (December 2005-April 2006) and then azathioprine (April-June 2006), which were both discontinued due to adverse effects. After the patient scored 6.5 on the Expanded Disability Status Scale and had 2 relapses in 2006, we initiated natalizumab therapy (300 mg monthly, starting September 2006). The patient improved significantly in ambulation and the relapse rate slowed as well.


Monoclonal antibodies in allergy; updated applications and promising trials.
Allergic disorders, as asthma, allergic rhinitis/rhinoconjunctivitis, atopic dermatitis, food allergies and anaphylaxis have an increasing burden in the general population and a growing body of evidence has shown that an increased interest has aroused to seek for more effective treatment strategies. Conventional pharmacotherapy by antihistamines, anti-leukotrienes, corticosteroids and bronchodilators can routinely control most of the cases, in addition to allergen avoidance which saves the date. Furthermore, allergen specific immunotherapy stands as the only curative method to treat the underlying cause of allergic immune response by induction of immune tolerance. However, response to pharmacotherapies can show diversity depending on the genotype and phenotype of the allergic disorders, which are known to be under the influence of multifactorial triggers. Thus, understanding the mechanisms of development of allergic disorders, in addition to selective description of the phenotypes can provide access to development of more specific therapies in order to control the disease progression. Monoclonal antibodies can be the major actors in this targeting process. Concerns about the safety, efficacy and long-term tolerability of these molecules always stand as a question for them, in order to gain indications for the treatment of allergic disorders. This review includes most recent developments and patents on usage of monoclonal antibodies for the treatment of allergic disorders.


Colorectal cancer--Prevention and detection.
The American Cancer Society estimates that during 1980, there will be approximately 114,000 new cases of colorectal cancer in the United States--second only to lung cancer (an expected 117,000 cases) in incidence for internal malignant neoplasms. There will be 53,000 deaths this year from colorectal cancer. The low five-year survival rate of 42% in related primarily to late diagnosis. Therefore effective methods of making an earlier diagnosis are important. The use of fecal occult blood testing and sigmoidoscopic examination (rigid or flexible) appear to be tools that will make earlier diagnoses of colorectal cancer. Colonoscopy and barium enema are indicated if symptoms of colorectal cancer are present or if indicated from findings noted on fecal occult blood testing or sigmoidscopy. Determinations of carcinoembryonic antigen levels are of no practical value in colorectal cancer screening. In asymptomatic patients, fecal occult blood testing is recommended annually beginning at age 50, while sigmoidoscopy should be performed at age 50, repeat in one year, then performed every three years. The two chief areas of interest in colorectal cancer prevention are the removal of neoplastic polyps at the time of endoscopy, and the role of nutrition to decrease fat and increase fiber in the diet.


Plasma exchange in the intensive care unit: a narrative review.
In this narrative review, we discuss the relevant issues of therapeutic plasma exchange (TPE) in critically ill patients. For many conditions, the optimal indication, device type, frequency, duration, type of replacement fluid and criteria for stopping TPE are uncertain. TPE is a potentially lifesaving but also invasive procedure with risk of adverse events and complications and requires close monitoring by experienced teams. In the intensive care unit (ICU), the indications for TPE can be divided into (1) absolute, well-established, and evidence-based, for which TPE is recognized as first-line therapy, (2) relative, for which TPE is a recognized second-line treatment (alone or combined) and (3) rescue therapy, where TPE is used with a limited or theoretical evidence base. New indications are emerging and ongoing knowledge gaps, notably regarding the use of TPE during critical illness, support the establishment of a TPE registry dedicated to intensive care medicine.


Selective inhibition of stemness through EGFR/FOXA2/SOX9 axis reduces pancreatic cancer metastasis.
Pancreatic cancer (PC) is difficult to defeat due to mechanism (s) driving metastasis and drug resistance. Cancer stemness is a major challenging phenomenon associated with PC metastasis and limiting therapy efficacy. In this study, we evaluated the pre-clinical and clinical significance of eradicating pancreatic cancer stem cells (PCSC) and its components using a pan-EGFR inhibitor afatinib in combination with gemcitabine. Afatinib in combination with gemcitabine significantly reduced KrasG12D/+; Pdx-1 Cre (KC) (P < 0.01) and KrasG12D/+; p53R172H/+; Pdx-1 Cre (KPC) (P < 0.05) derived mouse tumoroids and KPC-derived murine syngeneic cell line growth compared to gemcitabine/afatinib alone treatment. The drug combination also reduced PC xenograft tumor burden (P < 0.05) and the incidence of metastasis by affecting key stemness markers, as confirmed by co-localization studies. Moreover, the drug combination significantly decreases the growth of various PC patient-derived organoids (P < 0.001). We found that SOX9 is significantly overexpressed in high-grade PC tumors (P < 0.05) and in chemotherapy-treated patients compared to chemo-naïve patients (P < 0.05). These results were further validated using publicly available datasets. Moreover, afatinib alone or in combination with gemcitabine decreased stemness and tumorspheres by reducing phosphorylation of EGFR family proteins, ERK, FAK, and CSC markers. Mechanistically, afatinib treatment decreased CSC markers by downregulating SOX9 via FOXA2. Indeed, EGFR and FOXA2 depletion reduced SOX9 expression in PCSCs. Taken together, pan-EGFR inhibition by afatinib impedes PCSCs growth and metastasis via the EGFR/ERK/FOXA2/SOX9 axis. This novel mechanism of pan-EGFR inhibitor and its ability to eradicate CSC may serve as a tailor-made approach to enhance chemotherapeutic benefits in other cancer types.


Cerebellar Stroke: A Missed Diagnosis.
Cerebellar strokes account for less than 10% of all strokes but lead to significantly poor outcomes. Cerebellar strokes that are initially missed have a mortality rate of 40%, and half of the patients who survive have long-term deficits. The patient's history may provide clues that point to a cerebellar stroke. Signs and symptoms include vertigo, headache, vomiting and ataxia. It is important to note the presence of stroke risk factors, such as a history of strokes or transient ischemic attacks, diabetes mellitus, hypertension, hypercholesterolemia, advanced age, atrial fibrillation, and cigarette smoking. The importance of early and correct diagnosis is imperative to reduce morbidity and mortality.


Electrochemical Biosensing of Glucose Based on the Enzymatic Reduction of Glucose.
In this work, the enzyme aldehyde reductase, also known as aldose reductase, was synthesized and cloned from a human gene. Spectrophotometric measurements show that in presence of the nicotinamide adenine dinucleotide phosphate cofactor (NADPH), the aldehyde reductase catalyzed the reduction of glucose to sorbitol. Electrochemical measurements performed on an electrodeposited poly(methylene green)-modified gold electrode showed that in the presence of the enzyme aldehyde reductase, the electrocatalytic oxidation current of NADPH decreased drastically after the addition of glucose. These results demonstrate that aldehyde reductase is an enzyme that allows the construction of an efficient electrochemical glucose biosensor based on glucose reduction.


Arterial regeneration over absorbable prostheses.
Small-vessel arterial replacement by a prosthetic material elicits inflammatory and regenerative reactions that alter the patency rate of the resultant prosthesis-tissue complex. Woven absorbable polyglycolic acid prostheses, 24 mm in length, were implanted into adult rabbit aortas and followed for 7 1/2 months. At the time the animals were killed, 45 specimens were studied grossly and by arteriography, light and electron microscopy, immunohistology, and bursting-strength determinations. No rabbit died of aortic-related complications. Mild dilation occurred in 11% (five specimens), and intimal hyperplasia occurred in 13% (six specimens), with 76% (34 specimens) displaying parallel walls at the original 3- to 4-mm diameter. Microscopy showed that the prostheses were replaced by regenerating endothelialized vessels containing smooth musclelike myofibroblasts and dense fibroplasia, without thrombosis or infection. All withstood saline solution infusion at three to five times the systolic pressure. Results of these studies demonstrate conditions that permit arterial regeneration over absorbable scaffolds.


RBD-specific antibody response after two doses of different SARS-CoV-2 vaccines during the mass vaccination campaign in Mongolia.
The SARS-CoV-2 vaccination campaign began in February 2021 and achieved a high rate of 62.7% of the total population fully vaccinated by August 16, 2021, in Mongolia. We aimed to assess the initial protective antibody production after two doses of a variety of types of SARS-CoV-2 vaccines in the Mongolian pre-vaccine antibody-naïve adult population. This prospective study was conducted from March-April to July-August of 2021. All participants received one of the four government-proposed COVID-19 vaccines including Pfizer/BioNTech (BNT162b2), AstraZeneca (ChAdOx1-S), Sinopharm (BBIBP-CorV), and Sputnik V (Gam-COVID-Vac). Before receiving the first shot, anti-SARS-CoV-2 S-RBD human IgG titers were measured in all participants (n = 1833), and titers were measured 21-28 days after the second shot in a subset of participants (n = 831). We found an overall average protective antibody response of 84.8% (705 of 831 vaccinated) in 21-28 days after two doses of the four types of COVID-19 vaccines. Seropositivity and titer of protective antibodies produced after two shots of vaccine were associated with the vaccine types, age, and residence of vaccinees. Seropositivity rate varied significantly between vaccine types, 80.0% (28 of 35) for AstraZeneca ChAdOx1-S; 97.0% (193 of 199) for Pfizer BNT162b2; 80.7% (474 of 587) for Sinopharm BBIBP-CorV, and 100.0% (10 of 10) for Sputnik V Gam-COVID-Vac, respectively. Immunocompromised vaccinees with increased risk for developing severe COVID-19 disease had received the Pfizer vaccine and demonstrated a high rate of seropositivity. A high geometric mean titer (GMT) was found in vaccinees who received BNT162b2, while vaccinees who received ChAdOx1-S, Sputnik V, and BBIBP-CorV showed a lower GMT. In summary, we observed first stages of the immunization campaign against COVID-19 in Mongolia have been completed successfully, with a high immunogenicity level achieved among the population with an increased risk for developing severe illness.


Appropriateness of the Use of Magnetic Resonance Imaging in the Diagnosis and Treatment of Wrist Soft Tissue Injury.
When diagnosing wrist soft tissue injury, the authors hypothesize that magnetic resonance imaging is used injudiciously and is associated with unnecessary cost. A retrospective review was conducted of patients aged 20 to 60 years who underwent magnetic resonance imaging for possible wrist soft tissue injury at a tertiary care center between 2009 and 2014. Treatment recommendation was classified as nonoperative, operative, or equivocal. If the magnetic resonance imaging-directed treatment recommendation differed from the pre-imaging recommendation, it was noted that the imaging influenced patient care (impact study). The cost estimate of an impact study was calculated by dividing the total studies performed by the number of studies that impacted the treatment recommendation and multiplying this value by the institutional wrist magnetic resonance imaging cost ($2246 in 2016). One hundred forty patients were included. Magnetic resonance imaging affected treatment recommendation in 28 percent of patients. Independent predictors of impact on treatment recommendation were "question specific injury" (OR, 9.46; 95 percent CI, 3.18 to 28.16; p < 0.001) and "question scapholunate injury" (OR, 2.88; 95 percent CI, 1.21 to 6.88; p = 0.02). The only independent predictor of surgery was ordering physician (hand surgeon) (OR, 3.69; 95 percent CI, 1.34 to 10.13; p = 0.01). The cost of an impact study ordered by a non-hand surgeon versus a hand surgeon was $13,359 versus $6491, respectively. The provider must carefully consider the pretest probability of ordering a study that will affect treatment recommendation. Injudicious screening with magnetic resonance imaging ($15,565) incurred a cost nearly seven times the cost of the one imaging scan ($2246) before impacting one treatment recommendation. In the current era of cost containment and bundled payment, diagnostic test probability must be appreciated to guide physician ordering practices.


Undifferentiated small round cell sarcoma with t(4;19)(q35;q13.1) CIC-DUX4 fusion: a novel highly aggressive soft tissue tumor with distinctive histopathology.
A subset of small round cell sarcomas remains difficult to classify. Among these, a rare tumor harboring a t(4;19)(q35;q13.1) with CIC-DUX4 fusion has been described. The aim of this study is to better understand its clinicopathologic features. Four cases of CIC-DUX4 sarcoma, all arising in adults (3 women, 1 man, aged 20 to 43 y), were identified using conventional cytogenetic, reverse transcription polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) methods. All 4 tumors demonstrated CIC-DUX4 fusion transcript by both RT-PCR and FISH and CIC rearrangement by FISH. Cytogenetic results from 2 tumors showed t(4;19)(q35;q13.1) occurring as part of a simple karyotype in 1 tumor and as part of a complex karyotype in the other, the latter from a postchemotherapy specimen. Both tumors harbored trisomy 8 and lacked any other known sarcoma-associated translocation. No EWS or SYT rearrangements were detected by RT-PCR or FISH. The tumors had small round cell morphology with a distinctive constellation of histologic features including extensive geographic necrosis, mild nuclear pleomorphism with coarse chromatin and prominent nucleoli, clear cell areas, and focal myxoid matrix. Only focal staining for CD99 was present in each tumor. Two had very focal cytokeratin staining. All tumors were negative for desmin, myogenin, TLE-1, and S100 protein, whereas nuclear INI-1 staining was retained. The tumors were highly aggressive, and all patients died of disseminated disease within 16.8 months. CIC-DUX4 sarcoma represents a novel translocation-associated sarcoma with distinctive histopathologic features and rapid disease progression.


The role of extracellular matrix in the migration and differentiation of parietal endoderm from teratocarcinoma embryoid bodies.
Embryoid bodies formed from teratocarcinoma stem cells differentiate an outer layer consisting of parietal and visceral endoderm or of visceral endoderm exclusively. We have previously shown that when these embryoid bodies are plated on collagen-coated substrates a parietal endoderm-like cell migrates onto the substrate, whereas all of the visceral endoderm remains associated with the stem cell mass, suggesting a role for substrate contact in parietal endoderm differentiation. We now identify fibronectin as the migration-promoting component in these cultures, and note that laminin and collagen type IV are 10-fold less effective at promoting both attachment and endoderm outgrowth. The RGDS tetrapeptide (arg-gly-asp-ser) from the cell attachment domain of fibronectin can specifically block attachment and outgrowth on both fibronectin- and laminin-coated substrates. In addition, the involvement of the 140-kD fibronectin receptor is demonstrated using an antibody directed against this molecule.


Sensitive allele-specific real-time PCR test for mutations in BRAF codon V600 in skin melanoma.
Mutations at BRAF codon V600 are used as predictive biomarkers for targeted therapy of skin melanoma. Here, a simple sensitive test to detect mutations of BRAF-V600 was developed using real-time PCR with allele-specific primers and TaqMan probes. Two versions of the test using sense and antisense allele-specific primers were designed and evaluated. The test detected 1% mutant allele V600E/K in 10 ng DNA standard made from wild-type human DNA spiked with BRAF-V600E or the V600K plasmid. The test was validated on clinical formalin-fixed paraffin-embedded samples of skin melanoma using pyrosequencing as a reference method. In the clinical samples, we detected the common mutation V600E, as well as the rare mutations V600K, V600E2 (codon GAA), V600E2 K601del, V600D-K601del, and V600R. In comparison with pyrosequencing, both versions of the test had 100% specificity with sensitivities of 97 and 86% for sense and antisense allele-specific primers, respectively. Using the PCR test with sense allele-specific primers, mutations in V600 were found in 33 of 51 Russian patients (64.7%) with cutaneous melanoma. This closed-tube real-time PCR test can be used as a simple and sensitive assay for mutations of BRAF-V600 in cutaneous melanoma.


Inducible nitric oxide synthase, nitrotyrosine and apoptosis in gastric adenocarcinomas and their correlation with a poor survival.
To detect the presence of inducible nitric oxide synthase (iNOS), nitrotyrosine (NT) and apoptosis in gastric adenocarcinomas and their possible correlations with the clinicopathological characteristics and prognosis of gastric adenocarcinoma. Sixty-six specimens of gastric adenocarcinoma and corresponding adjacent normal gastric tissues were studied. Immunohistochemistry was employed to localize iNOS and NT protein and an immunohistochemical scoring system was used. The occurrence of apoptotic cell death (apoptotic index (AI)) was analyzed by the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling (TUNEL) method. Results showed that iNOS expression was detected at an intermediate or high level in 41 of 66 (62%) specimens of gastric adenocarcinoma. NT expression was 58%. Neither of them was found in the normal gastric tissues; there were significant positive correlations among iNOS expression, NT expression and AI. Many clinicopathologic characteristics of gastric adenocarcinoma, such as tumor size, depth of invasion, lymph node metastasis and TNM staging, were related to iNOS and NT expressions (P<0.05). In 66 surviving patients, the 5-year survival rate of 41 patients who had tumors with intermediate or high iNOS expressions and high AIs (4.09%; 19.96%) was significantly lower than that of 25 patients who had tumors with negative or low iNOS expressions and low AIs (0.79%; 47.14%) (P = 0.001). COX's multivariate analysis revealed that the iNOS expression was identified as one of the significant independent prognostic factors predictive of a poor survival (relative risk (RR) = 2.69). NO produced by iNOS may play a stronger role in promoting gastric adenocarcinoma growth than in suppressing its growth. iNOS and NT expressions by gastric adenocarcinoma may correlate with a poor survival.


Chick noggin is expressed in the organizer and neural plate during axial development, but offers no evidence of involvement in primary axis formation.
We have cloned and examined the early developmental expression of the chick homolog of noggin, a gene originally isolated in Xenopus that can dorsalize gastrular mesoderm and induce anterior neural tissue from gastrular ectoderm when expressed experimentally. Chick noggin is expressed at relatively low levels, but at sites equivalent to those seen in amphibian development, namely Hensen's node and the endo- and mesodermal head process. There is also diffuse expression in the early CNS, centered on the ventral midline, and later hindbrain-associated expression. Since the earlier of these expression sites are consistent with endogenous organizer functions suggested by the properties of the protein in Xenopus experiments, we have used recombinant mammalian Noggin protein secreted by CHO cells in tests for developmental disturbance on the early gastrula-staged chick blastoderm. Comparable tests sensitively detect effects, on chick, of various other secreted proteins that simulate or replicate early developmental signals in Xenopus. We have been unable to observe such effects with a range of Noggin concentrations including those that dramatically dorsalize Xenopus ventral marginal zones. To illustrate effects observed in such tests with secreted proteins active on early stages, we show results with the known Xenopus ventralizer Bone Morphogenetic Protein 4 (BMP-4).


[Molecular detection of yellow fever virus in human sera and mice brains].
A molecular method for the diagnosis of yellow fever virus infection was developed based on reverse transcription (RT) followed by polymerase chain reaction (PCR) amplification. Examinations were conducted on lyophilized sera from 3 fatal yellow fever cases and 4 fresh sera from 3 fatal cases and one from a symptomatic patient (positive IgM against yellow fever virus). Sera were extracted with TRIZOL-LS to isolate viral RNA for RT treatment and the PCR reaction included 2 primers sets designed specifically for yellow fever virus: sense, JM2104 (5'-CGTTGGGAGAGGAGATTC-3') y JM2249 (5'-TTCTTCACTTCGGTTGGG-3'), and antisense, JM2673 (5'-TCATCTGCCCTGCTTCTC-3') y JM2751 (5'-CCTCTCTGGTAAACATTCT-3'). The technique for demonstrating the yellow fever virus in tissue samples was used in infected mice brains treated with lysis buffer before RNA extraction. PCR reactions were evaluated in agarose gels where single bands of the expected size for each primers pair (569 bp and 502 bp) were observed for all serum samples. In addition, the results for 2 fresh positive sera were supported by histopathologic finding of yellow fever virus. The RT-PCR method permits a rapid and specific demonstration of the presence of yellow fever virus.


[Omega-3 fatty acids and astaxanthin in health and disease. Recent knowledges].
At present, medicine is aimed to the treatment of lesions. Instead, it would be right to develop the maintenance of normal health. A number of authorities have recently recommended increases in intake of omega-3 fatty acids and astaxanthin for the health of general population. Omega-3 are necessary to provide the optimal function of cellular membrane in health and in disease states. It is well known how at least two servings of fish a week, or dietary supplementation of fatty acids omega-3, should be taken to obtain the health benefits of this essential nutrient. Astaxanthin is a powerful biological antioxidant. This property has been implicated in its various biological activities demonstrated in both experimental animals and clinical studies. For the recent evidence of the contemporary presence of omega-3 and astaxanthin in oil of Wild Pacific Salmon Sockeye, a review has been effected for the evaluation of a possible role of such association for the health promotion.


Intraspecific scaling and early life history determine the cost of free-flight in a large beetle (Batocera rufomaculata).
The scaling of the energetic cost of locomotion with body mass is well documented at the interspecific level. However, methodological restrictions limit our understanding of the scaling of flight metabolic rate (MR) in free-flying insects. This is particularly true at the intraspecific level, where variation in body mass and flight energetics may have direct consequences for the fitness of an individual. We applied a 13 C stable isotope method to investigate the scaling of MR with body mass during free-flight in the beetle Batocera rufomaculata. This species exhibits large intraspecific variation in adult body mass as a consequence of the environmental conditions during larval growth. We show that the flight-MR scales with body mass to the power of 0.57, with smaller conspecifics possessing up to 2.3 fold higher mass-specific flight MR than larger ones. Whereas the scaling exponent of free-flight MR was found to be like that determined for tethered-flight, the energy expenditure during free-flight was more than 2.7 fold higher than for tethered-flight. The metabolic cost of flight should therefore be studied under free-flight conditions, a requirement now enabled by the 13 C technique described herein for insect flight.


Legg-Calvé-Perthes disease at 100: a review of evidence-based treatment.
The year 2010 is the 100th anniversary of the publication of the first 3 reports describing Legg- Calve-Perthes disease (LCPD). This paper summarizes available evidence previously published and discussed at the several world conferences honoring the occasion. Relevant articles with evidence-based data regarding the efficacy of treatment methods for LCPD were reviewed by the author. The reviewed studies noted 3 factors related to outcome in patients treated for LCPD as follows: the age at onset, the classification of severity of femoral head involvement, and the type of treatment. In patients over age 8 at onset, surgical treatment with femoral varus osteotomy or Salter innominate osteotomy was associated with improved Stulberg outcomes compared with nonoperative treatment, in those who had lateral pillar B or B/C border class involvement. In the Wiig et al study, patients over age 6 with Catterall 3, 4 classification had better outcomes with these surgical treatment methods compared with nonoperative methods. Children under age 6 at onset had a good prognosis except for a small number of patients between age 4 and 6 years with lateral pillar C involvement. There is valid evidence of an association between surgical treatment of certain patients with LCPD and improved radiographic outcome.


Characterization and expression patterns of let-7 microRNA in the silkworm (Bombyx mori).
lin-4 and let-7, the two founding members of heterochronic microRNA genes, are firstly confirmed in Caenorhabditis elegans to control the proper timing of developmental programs in a heterochronic pathway. let-7 has been thought to trigger the onset of adulthood across animal phyla. Ecdysone and Broad-Complex are required for the temporal expression of let-7 in Drosophila melanogaster. For a better understanding of the conservation and functions of let-7, we seek to explore how it is expressed in the silkworm (Bombyx mori). One member of let-7 family has been identified in silkworm computationally and experimentally. All known members of this family share the same nucleotides at ten positions within the mature sequences. Sequence logo and phylogenetic tree show that they are not only conserved but diversify to some extent among some species. The bmo-let-7 was very lowly expressed in ova harvested from newborn unmated female adult and in individuals from the first molt to the early third instar, highly expressed after the third molt, and the most abundant expression was observed after mounting, particularly after pupation. The expression levels were higher at the end of each instar and at the beginning of each molt than at other periods, coinciding with the pulse of ecdysone and BR-C as a whole. Using cultured ovary cell line, BmN-SWU1, we examined the effect of altered ecdysone levels on bmo-let-7 expression. The expression was also detected in various tissues of day 3 of the fifth instar and of from day 7 of the fifth to pupa, suggesting a wide distributing pattern with various signal intensities. bmo-let-7 is stage- and tissue-specifically expressed in the silkworm. Although no signals were detected during embryonic development and first larval instar stages, the expression of bmo-let-7 was observed from the first molt, suggesting that it might also function at early larval stage of the silkworm. The detailed expression profiles in the whole life cycle and cultured cell line of silkworm showed a clear association with ecdysone pulse and a variety of biological processes.


Hsa-microRNA-181a is a regulator of a number of cancer genes and a biomarker for endometrial carcinoma in patients: a bioinformatic and clinical study and the therapeutic implication.
The aberrant expression of human microRNA-181a-1 (hsa-miR-181a) has been implicated in the pathogenesis of various cancers, serving as an oncogene or a tumor suppressor. However, the role of hsa-miR-181a in the pathogenesis of endometrial carcinoma (EC) and its clinical significance are unclear. This study aimed to search for the molecular targets of hsa-miR-181a using bioinformatic tools and then determine the expression levels of hsa-miR-181a in normal, hyperplasia, and EC samples from humans. To predict the targets of hsa-miR-181a, ten different algorithms were used, including miRanda-mirSVR, DIANA microT v5.0, miRDB, RNA22 v2, TargetMiner, TargetScan 6.2, PicTar, MicroCosm Targets v5, and miRWALK. Two algorithms, TarBase 6.0 and miRTarBase, were used to identify the validated targets of hsa-miR-181a-5p (a mature product of hsa-miR-181a), and the web-based Database for Annotation, Visualization and Integrated Discovery (DAVID) 6.7 was used to provide biological functional interpretation of the validated targets of hsa-miR-181a-5p. A total of 78 formalin-fixed, paraffin-embedded tissue specimens from 65 patients and 13 healthy subjects were collected and examined, including normal endometrium (n=13), endometrial hyperplasia (n=18), and EC (37 type I and 10 type II EC cases). Our bioinformatic studies have showed that hsa-miR-181a might regulate a large number of target genes that are important in the regulation of critical cell processes, such as cell fate, cell survival, metabolism, and cell death. To date, 313 targets of hsa-miR-181a have been validated, and 22 of these targets are cancer genes. The precision of predictions by all the algorithms for hsa-miR-181a-1's targets was low. Many of these genes are involved in tumorigenesis of various cancers, including EC, based on the DAVID and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. In comparison with normal endometrial tissue, the expression level of hsa-miR-181a was significantly increased in type I and type II EC (P<0.05), and type II EC exhibited a significant higher expression level of hsa-miR-181a than that in type I EC (P<0.05). In addition, there was a significant increase in the expression level of hsa-miR-181a in type II EC compared with endometrial hyperplasia (P<0.05). Taken together, these results suggest that hsa-miR-181a may serve as an oncogene in endometrial tumorigenesis and that hsa-miR-181a might be used as a new biomarker in the prediction of prognosis of EC in clinical practice. More functional and mechanistic studies are needed to validate the role of hsa-miR-181a in the development, progression, and metastasis of EC.


Microvascular network alterations in retina of subjects with cerebral small vessel disease.
Novel retinal imaging techniques have enabled the assessment of quantitative vascular parameters, which provide information on the microvasculature before the appearance of retinopathy signs. Advances in neuroimaging have revealed that cerebral microbleeds (CMB) - besides lacunar infarcts and white matter lesions (WML) - may be a novel marker of cerebral small vessel disease. We examine whether quantitative retinal vascular parameters are related to cerebral small vessel disease in a Chinese population. Participants from Epidemiology of Dementia in Singapore Study underwent comprehensive examinations, including 3-Tesla cranial magnetic resonance imaging and retinal-photography. Retinal vascular parameters (caliber, tortuosity, fractal dimension) were measured from photographs using a semi-automated computer-assisted program. Lacunar infarcts and CMB were visually graded. Total brain and WML volume were obtained using a validated segmentation tool. A total of 261 subjects were included, of whom 36 had lacunar infarcts, 29 had severe WML, and 83 had CMB. In age-sex-adjusted models, narrower retinal arteriolar caliber, wider venular caliber and smaller arteriolar fractal dimension were associated with presence of multiple CMB. In contrast, no association was found with lacunar infarcts and WML volume. After multivariate adjustments, associations of venular caliber, arteriolar fractal dimensions and arteriolar tortuosity with CMB remained statistically significant. In conclusion, subjects with early structural changes in retinal microvasculature were more likely to have CMBs, supporting hypothesis that CMB may be an early manifestation of cerebral small vessel disease.


PROLIFERATIVE ACTIVITY OF THE LYMPHATIC TISSUES OF RATS AS STUDIED WITH TRITIUM-LABELED THYMIDINE.
Cytokinetic data are presented, employing quantitation of H(3)DNA in the lymphatic tissues of normal rats serially sacrificed after H(3)Tdr administration. A marked difference in the patterns of initial labeling and label loss was observed between the thymus and peripheral lymphatic tissue. The data are compatible with other indications of rapid cell renewal in the thymus. There is suppression of initial uptake of H(3)Tdr into the DNA of each large lymphocytic progenitor cell in the thymus, apparently because of a feedback of thymidine containing material from small lymphocytes in the thymus. Depletion of the thymus of small cells, as by operative stress or whole body x-ray, leads to a marked increase in the uptake of H(3)Tdr into the DNA of large thymocytes. This finding, which is in agreement with the previous findings of Sugino et al. (33, 34) suggesting transfer of thymine nucleotides from small thymus lymphocytes to precursor cells, may or may not be related to the apparent transfer of DNA label between thymic cells. The evidence for the latter consists of the curvilinear dilution of the DNA label in the thymus proliferating cell population and the relationship between the rate of DNA label dilution in large cells and the H(3)DNA in the small cells in the thymus. After the DNA label in progenitor cells in the thymus and lymph nodes has entered the small cell population, the subsequent dilution of grains in these dividing cells follows the same slope as the loss of radioactivity from the entire lymph node. There is a long retention of some H(3)DNA label in the dividing lymph node cell population. This suggests that the loss of radioactivity from the dividing cells and from the small cell population as a whole occurs equally. This pattern prevails regardless of whether the percentage of large and small cells is altered experimentally. These findings can be explained by an interchange of the DNA nuclear label between small lymphocytes and large lymphocytes. This could occur by some process such as phagocytosis or pinocytosis, or by transformation of the small lymphocyte into a large, dividing cell. The data fit best with the latter possibility. All or any of these mechanisms would lead to an equilibration of the DNA label between large and small cells. This finding prevents the assignment of a finite life span to lymphocytes on the basis of DNA labeling kinetics. Nevertheless, there appear to be at least two different types of lymphocytes. One, the "thymus-type" lymphocyte, is found in the thymus cortex, bone marrow and germinal centers of lymphoid follicles. The other type, found abundantly in the widespread peripheral lymphatic tissue, shows a very prolonged retention of DNA label and is believed to be the recirculating, "immunologically committed" cells described by others. These cells do not appear to enter the thymus cortex.


Cost per RN hired.
Costs of recruiting, hiring, and training new staff members can be significant. This article demonstrates a method for analyzing the components of these costs to target areas where improved efficiency can lead to lower costs.


Treatment-induced menstrual changes in very young (<35 years old) breast cancer patients.
To evaluate the treatment-induced menstrual changes in very young (< 35 years old) breast cancer patients. We retrospectively examined the clinical records of 160 patients, ranging in age from 18 to 34 years old (median age, 32 years), treated between June 1992 and December 2002. One hundred twenty patients underwent mastectomy and 40 underwent breast conserving surgery. Postoperatively, 80 patients were treated with alkylating agent-based chemotherapy regimens (CMF) and 80 with anthracycline-based regimens (AD). In addition, 57 patients received adjuvant radiotherapy, and 77 received anti-estrogen therapy. Treatment-induced menstrual changes and present menstrual status were evaluated from hospital records and by one-to-one interviews. The median follow-up period was 54 months (range, 29-156 months). Treatment-induced menstrual change (amenorrhea) was occurred in 59 (36.9%) patients, 25 (31.3%) of those treated with CMF and 34 (42.5%) with AD (p=0.142). Amenorrhea occurred after a median 2 cycles of chemotherapy (range, 1-6 cycles). Menstruation resumed in 49 (83.1%) patients, 20 (80%) of those treated with CMF and 29 (85.3%) with AD (p=0.6). Median time to resumption of menstruation was median 3.5 months (range, 1-18 months) after amenorrhea. Disease recurred in 10 (16.9%) patients who experienced treatment-induced menstrual changes and in 18 (17.8%) of those who did not (p=0.89). Although the overall incidence of treatment-induced menstrual change in breast cancer patients under age 35 was similar to that reported elsewhere, the rate of recovery from these change is higher. We observed no difference between CMF and AD treated patients in rates of amenorrhea or recovery from these changes.


X-ray absorption spectroscopy and resonant inelastic scattering study of the first lithiation cycle of the Li-ion battery cathode Li(2-x)MnSiO4.
We employ soft X-ray absorption spectroscopy and resonant inelastic X-ray scattering spectroscopy to study the redox behavior in the first lithiation/delithiation cycle of Li(2-x)MnSiO4 (4.0-4.6 V). For extraction of lithium ions up to an end potential of 4.1 V, we do not detect any change in the oxidation state for the expected redox-active Mn atom, instead the electronic structure of the Si-O network is affected. Above 4.1 V, there is an abrupt change in the oxidation state of the Mn-ions, from 2+ to 4+, which is accompanied by a complete loss of long range order in the material, as detected by X-ray diffraction. Further lithium extraction leads to progressive loss of crystallinity of Li(2-x)MnSiO4, rather than formation of a new structure, explaining the measured first-cycle capacity loss of this material. Our results suggest that future improvement of the crystalline stability of the material, particularly with respect to the SiO4 network, is required to harness the full charge capacity of Li(2-x)MnSiO4.


Non-viral, Tumor-free Induction of Transient Cell Reprogramming in Mouse Skeletal Muscle to Enhance Tissue Regeneration.
Overexpression of Oct3/4, Klf4, Sox2, and c-Myc (OKSM) transcription factors can de-differentiate adult cells in vivo. While sustained OKSM expression triggers tumorigenesis through uncontrolled proliferation of toti- and pluripotent cells, transient reprogramming induces pluripotency-like features and proliferation only temporarily, without teratomas. We sought to transiently reprogram cells within mouse skeletal muscle with a localized injection of plasmid DNA encoding OKSM (pOKSM), and we hypothesized that the generation of proliferative intermediates would enhance tissue regeneration after injury. Intramuscular pOKSM administration rapidly upregulated pluripotency (Nanog, Ecat1, and Rex1) and early myogenesis genes (Pax3) in the healthy gastrocnemius of various strains. Mononucleated cells expressing such markers appeared in clusters among myofibers, proliferated only transiently, and did not lead to dysplasia or tumorigenesis for at least 120 days. Nanog was also upregulated in the gastrocnemius when pOKSM was administered 7 days after surgically sectioning its medial head. Enhanced tissue regeneration after reprogramming was manifested by the accelerated appearance of centronucleated myofibers and reduced fibrosis. These results suggest that transient in vivo reprogramming could develop into a novel strategy toward the acceleration of tissue regeneration after injury, based on the induction of transiently proliferative, pluripotent-like cells in situ. Further research to achieve clinically meaningful functional regeneration is warranted.


Phase II Study of Weekly Amrubicin for Refractory or Relapsed Non-small Cell Lung Cancer.
Amrubicin is usually administered on days 1-3 every 3 weeks by intravenous infusion. However, it causes severe hematological toxicity, especially febrile neutropenia. It was reported that weekly administration confers higher dose intensity, less severe adverse events, and anti-tumor activity that is as effective as that of treatment with a conventional schedule. Weekly amrubicin was administered at a dose of 60 mg/m2 on days 1 and 8 every 3 weeks. The primary endpoint was overall response rate. A total of 33 patients were enrolled. The overall response rate was 6.1% (95% confidence interval(CI)=0.7-20.2%) and the disease control rate after 2 months was 51.5%. The median progression-free survival was 2.93 months. Febrile neutropenia was observed in only two patients. The primary endpoint was not met in this study. However, weekly amrubicin achieved a high disease control rate and good tolerability.


Walking behaviors reported in the American Time Use Survey 2003-2005.
We report walking for shopping, exercise, transportation, and walking the dog, among other sources captured in the 2003 to 2005 American Time Use Survey (ATUS). We extracted and analyzed 8 walking behaviors (by sex, age, education level, and race/ethnicity) from 24 hours of activities recalled by telephone interview for 15,175 males and 19,518 females age<15 years. On any given day in 2003 to 2005, 45.8% of Americans participated in a median of 45 minutes of any walking activities; 31.6% walked for shopping purposes, 12.5% walked for transportation, 4.8% walked for exercise, and 2.5% walked the dog. College-educated respondents more commonly reported walking while shopping, walking for exercise, and dog walking. Those with less than a high school education more commonly reported walking for transportation. Despite limitations identified in imputing explicit and implicit performance of walking behaviors in the ATUS, Americans engage in a wide variety of walking behaviors that are not well represented by surveys focused only on leisure-time behaviors. Public health implications include increased availability of multiple and varied opportunities for walking, especially through environmental shifts toward more walkable places and destinations and policy shifts that support walking behaviors over competing transportation modes.


Comparative Anticancer Potentials of Taxifolin and Quercetin Methylated Derivatives against HCT-116 Cell Lines: Effects of O-Methylation on Taxifolin and Quercetin as Preliminary Natural Leads.
Six flavonoids present in Pulicaria jaubertii, i.e., 7,3'-di-O-methyltaxifolin (1), 3'-O-methyltaxifolin (2), 7-O-methyltaxifolin (3), taxifolin (4), 3-O-methylquercetin (5), and quercetin (6), were tested for their anticancer activities. The methylated flavonoids, compounds 1-3 and 5, were evaluated for their anticancer activities in comparison to the non-methylated parent flavonoids taxifolin (4) and quercetin (6). The structures of the known compounds were reconfirmed by spectral analyses using 1H and 13C NMR data comparisons and HRMS spectrometry. The anticancer activity of these compounds was evaluated in colon cancer, HCT-116, and noncancerous, HEK-293, cell lines using the MTT antiproliferative assays. The caspase-3 and caspase-9 expressions and DAPI (4', 6-diamidino-2-phenylindole) staining assays were used to evaluate the apoptotic activity. All the compounds exhibited antiproliferative activity against the HCT-116 cell line with IC50 values at 33 ± 1.25, 36 ± 2.25, 34 ± 2.15, 32 ± 2.35, 34 ± 2.65, and 36 ± 1.95 μg/mL for compounds 1 to 6, respectively. All the compounds produced a significant reduction in HCT-116 cell line proliferation, except compounds 2 and 6. The viability of the HEK-293 normal cells was found to be significantly higher than the viability of the cancerous cells at all of the tested concentrations, thus suggesting that all the compounds have better inhibitory activity on the cancer cell line. Apoptotic features such as chromatin condensation and nuclear shrinkage were also induced by the compounds. The expression of caspase-3 and caspase-9 genes increased in HCT-116 cell lines after 48 h of treatment, suggesting cell death by the apoptotic pathways. The molecular docking studies showed favorable binding affinity against different pro- and antiapoptotic proteins by these compounds. The docking scores were minimum as compared to the caspase-9, caspase-3, Bcl-xl, and JAK2.


The Effect of Electronical Film on the Anxiety of Patients Candidate for Lumbar Disc Surgery.
This study aimed at investigating the effect of showing surgery educational documentary film on the anxiety of patients candidate for lumbar disc surgery. This study, as a randomized clinical trial, was conducted in 2018 on 60 patients undergoing lumbar disc surgery, Iran. The patients were divided into two groups of intervention and control (N = 30). An educational film was shown to the patients of the intervention group for 20 min and the control group was provided with the ward's routine trainings. All patients completed demographic characteristics questionnaire and the Spielberger State-Trait Anxiety Inventory (SSTAI) on the admission day, 1 day before the surgery, and 2 h before the surgery. SSTAI was recompleted by the patients. Data analysis was performed using independent t-test, Chi-square, Mann-Whitney test, and paired t-test. Before the intervention, the mean score of the state (obvious) and trait (hidden) anxieties was not significantly different between the two groups, but after the intervention, the mean [standard deviation (SD)] score of the state anxiety in the intervention group was significantly lower than that of the control group [mean (SD) = 40.78 (10.34) vs. 47.45 (10.33), F 10,33 = 58, p = 0.01]. In addition, after the intervention, the mean (SD) anxiety score of the patients in the intervention group was significantly lower than that of the control group [mean (SD) = 38.65 (11.01) vs. 44.71 (10.34), F 10,34 = 58, p = 0.03). The results showed that educational film reduces the patients' level of anxiety before the surgery. As such, it is recommended that these trainings be included in preoperative nursing practices.


Symptoms of the schizophrenic negative syndrome.
The aim was an investigation of the symptom composition of the negative syndrome of schizophrenia. A hundred schizophrenic patients were assessed with various rating scales for positive and negative symptoms and typological criteria. A subgroup with a negative syndrome was defined, and a discriminant analysis performed using symptoms from the Scale for the Assessment of Negative Symptoms (SANS) as discriminant variables. The discriminant function classified 92% of patients correctly. All but four SANS symptoms (inappropriate affect, both attentional items and blocking) were significantly correlated with the discriminant function. With the exception of some items, the SANS seems to capture adequately the negative syndrome of schizophrenia.


Sodium reabsorption in aldosterone-sensitive distal nephron: news and contributions from genetically engineered animals.
The precise adaptation of renal sodium excretion to systemic needs is to a large extent achieved by the regulation of sodium re-absorption in the aldosterone-sensitive distal nephron. Transcellular sodium re-absorption by the segment-specific cells of the aldosterone-sensitive distal nephron (often called principal cells) is mainly controlled at the level of the expression and activity levels of the epithelial sodium channel, the apical amiloride-sensitive sodium influx pathway. Recent investigations have identified the first early aldosterone-induced proteins that act on epithelial sodium channel function in expression systems. Indirect evidence suggests that one of these aldosterone-induced proteins, the serum- and glucocorticoid-inducible protein kinase SGK1, plays a central integratory role in the control of epithelial sodium channel surface expression and activity, also in the mammalian kidney. Gene-modified animals lacking epithelial sodium channel subunits or expressing mutant subunits have substantiated the central role of the epithelial sodium channel in sodium re-absorption and blood pressure control, as well as for neonatal lung liquid clearance. Mice overexpressing or lacking specific hormones or their receptors have been used to study their role in sodium transport regulation, but the study of mouse physiology appears to lag behind the generation of gene-modified mice. Nonetheless, these new animal models have had a strong impact on research, by stimulating the integration of knowledge and techniques learned from reductionistic molecular approaches into tissue and animal studies, thus breaking down barriers and stimulating collaborations.


[The distribution of haptoglobin phenotypes among the population of Ukraine].
The results of investigation of haptoglobin (Hp) types in 596 donor blood samples in some towns of Ukraine (Dnepropetrovsk, Kharkov, Odessa, Kiev, Uzhgorod, Zhitomir) are presented. Three normal Hp types (Hp1-1, Hp2-1 and Hp2-2) have been found. The reliable interpopulation differences in the Hp types frequency were not found. On the whole the Hp types frequency in the type Hp1-1 comprised 12.7%. In the type Hp2-1-48.1% and in the type Hp2-2-36.5%. The frequency of the gene Hp1 is 0.38. The frequency of the Hp types and of the gene Hpl in Ukraine is similar to that in population of Eastern Europe and European Part of Russia.


Testing the McSad depression specific classification system in patients with somatic conditions: validity and performance.
Valuations of depression are useful to evaluate depression interventions offered to patients with chronic somatic conditions. The only classification system to describe depression developed specifically for valuation purposes is the McSad, but it has not been used among somatic patients. The aim of this study was to test the construct validity of the McSad among diabetes and cancer patients and then to compare the McSad to the commonly used EuroQol - 5 Dimensions (EQ-5DTM) classification system. The comparison was expected to shed light on their capacity to reflect the range of depression states experienced by somatic patients. Cross-sectional data were collected online from 114 diabetes and 195 cancer patients; additionally, 241 cancer patients completed part of the survey on paper. Correlational analyses were performed to test the construct validity. Specifically, we hypothesized high correlations of the McSad domains with depression (Center for Epidemiological Studies Depression Scale (CES-D) and the Patient Health Questionnaire (PHQ-9)). We also expected low/moderate correlations with self-esteem (Rosenberg Self-Esteem scale - RSE) and extraversion (Eysenck Personality Questionnaire Extraversion scale - EPQ-e). Multiple linear regression analyses were run so that the proportion of variance in depression scores (CES-D, PHQ-9) explained by the McSad could be compared to the proportion explained by the EQ-5D classification system. As expected, among all patients groups, we found moderate to high correlations for the McSad domains with the CES-D (.41 to .70) and the PHQ-9 (.52 to .76); we also found low to moderate correlations with the RSE (-.21 to .-48) and the EPQ-e (.18 to .31). Linear regression analyses showed that the McSad explained a greater proportion of variance in depression (CES-D, PHQ-9) (Diabetes: 73%, 82%; Cancer: 72%, 72%) than the EQ-5D classification system (Diabetes: 47%, 59%; Cancer: 51%, 47%). Findings support the construct validity of the McSad among patients with somatic conditions and demonstrate that it performs better than the EQ-5D classification system to reflect the range of depression states. For future valuation purposes, the McSad classification system could therefore be recommended to describe depression as experienced by patients with a chronic medical condition.


Unit-dose packaged drugs for treating malaria.
Unit-dose packaging of antimalarial drugs may improve malaria cure by making it easier for patients to take their treatment correctly. To summarize the effects of unit-dose packaged treatment on cure and treatment adherence in people with uncomplicated malaria. We searched the Cochrane Infectious Diseases Group Specialized Register (November 2004), CENTRAL (The Cochrane Library Issue 4, 2004), MEDLINE (1966 to November 2004), EMBASE (1980 to November 2004), LILACS (November 2004), conference proceedings, and reference lists of articles. We also contacted pharmaceutical companies, organizations, and researchers in the field. Randomized controlled trials (RCTs), cluster-RCTs, quasi-RCTs, and controlled before-and-after studies of unit-dose packaged drugs for treating uncomplicated malaria. We independently assessed study eligibility and methodological quality, and extracted data for an intention to treat analysis, where possible. We combined binary data using relative risk (RR) and the fixed-effect model, and presented them with 95% confidence intervals (CI). We attempted to contact study authors for additional information. Three quasi-RCTs (895 participants) and one cluster-RCT (6 health facilities) met the inclusion criteria. Trials were of poor methodological quality, and none adequately assessed treatment failure. Unit-dose packaged drugs (in conjunction with prescriber training and patient information) appeared to be associated with higher participant-reported treatment adherence in all trials.A meta-analysis of two trials (596 participants) showed that participant-reported treatment adherence was higher with blister-packed tablets compared with tablets in paper envelopes (RR 1.18, 1.12 to 1.25). Two trials using tablets in sectioned polythene bags as the intervention also noted an increase in participant-reported treatment adherence: the cluster-RCT (6 clusters) compared it with tablets in paper envelopes, and the other trial compared it with syrup in bottles (RR 2.15, 1.76 to 2.61; 299 participants). There is insufficient evidence to determine the effect of unit-dose packaged antimalarial drugs on treatment failure. Unit-dose packaging supported by prescriber training and patient information appears to improve participant-reported treatment adherence, but these data come from trials with methodological limitations.


How do research participants perceive "uncertainty" in genome sequencing?
The scope of uncertainty in genome sequence information has no rival in health-care delivery. We present data from adults participating in a National Institutes of Health study using this technology, in which perceptions of uncertainty are hypothesized to be key in predicting decisions to learn and act on genome health information. We conducted six professionally moderated focus groups with 39 randomly selected ClinSeq participants varying on whether they had coronary heart disease and had received prior sequence results. We elicited perceptions of the uncertainties associated with genome sequencing using written prompts. Participants perceived uncertainty as a quality of genome information. The majority of participants characterized uncertainty of sequencing information as "changing, fluid, developing, or ground breaking." These responses led to anticipation of more optimistic future outcomes. Fewer participants described uncertainty as "questionable, less accurate, limited, or poorly understood." These perceptions seemed to undermine participants' faith in genome information, leading to feelings of disillusionment. Our findings suggest that perceptions of uncertainty are related to epistemological beliefs that inform expectations for the information. Interventions that promote realistic expectations of genome sequencing may mitigate negative responses to uncertainty.