Management of acute severe ulcerative colitis.
The management strategy of acute severe ulcerative colitis has evolved over the past decade from being entirely restricted to twin choices of intravenous steroids or colectomy to include colon rescue therapies like cyclosporin as well as infliximab. However it still remains a medical emergency requiring hospitalization and requires care from a multidisciplinary team comprising of a gastroenterologist and a colorectal surgeon. The frame shift in management has been the emphasis on time bound decision making with an attempt to curtail the mortality rate to below 1%. Intravenous corticosteroids are the mainstay of therapy. Response to steroids should be assessed at day 3 of admission and partial/non-responders should be considered for alternative medical therapy/surgery. Medical rescue therapies include intravenous cyclosporin and infliximab. Cyclosporin is administered in a dose of 2 mg/kg per day and infliximab is administered as a single dose intravenous infusion of 5 mg/kg. Approximately 75% patients have short term and 50% patients have long term response to cyclosporin. Long term response to cyclosporin is improved in patients who are thiopurine naïve and are started on thiopurines on day 7. Infliximab also has a response rate of approximately 70% in short term and 50% in long term. Both cyclosporin and infliximab are equally efficacious medical rescue therapies as demonstrated in a recent randomized control trial. Patients not responding to infliximab or cyclosporin should be considered for colectomy.


Renal denervation, adjusted drugs, or combined therapy for resistant hypertension: A meta-regression.
The objective of this study is to systematically evaluate the efficacy of renal denervation (RD), adjusted drugs, or combined therapy for resistant hypertension (RH) through a systematic review and meta-analysis of controlled studies.Publications were comprehensively searched. Studies that investigated the effects of RD and/or adjusted drugs in lowering blood pressure (BP) were included. After quality assessment and data extraction, subgroup analyzes were first performed according to blinding method. Meta-regression and inverted funnel plots were also conducted.A total of 13 studies containing 1604 RH patients were included. Compared with control, the meta-analysis showed that RD significantly reduced office-based BP and ambulatory BP in 6 months in the unblinded studies, while no significant difference was found in the blinded studies. Meta-regression demonstrated the significant influence of blinding method on BP reduction, and further analysis revealed a significant BP reduction compared with baseline even in the control arm of blinded studies. RD had similar effects compared with adjusted drugs, and combined therapy seemed to further reduce the level of BP.The efficacy of RD was different between blinded and unblinded studies, and our data revealed a significant BP-lowering effect in the control arm of blinded studies, which was helpful to explain this finding. Furthermore, RD seemed to be equivalent to adjusted drugs, and also we suggested a potential advantage of combined therapy of RD and adjusted drugs compared with monotherapy for RH. However, more studies are warranted to better address the issue.


Heterologous expression of Streptococcus mutans Cnm in Lactococcus lactis promotes intracellular invasion, adhesion to human cardiac tissues and virulence.
In S. mutans, the expression of the surface glycoprotein Cnm mediates binding to extracellular matrix proteins, endothelial cell invasion and virulence in the Galleria mellonella invertebrate model. To further characterize Cnm as a virulence factor, the cnm gene from S. mutans strain OMZ175 was expressed in the non-pathogenic Lactococcus lactis NZ9800 using a nisin-inducible system. Despite the absence of the machinery necessary for Cnm glycosylation, Western blot and immunofluorescence microscopy analyses demonstrated that Cnm was effectively expressed and translocated to the cell wall of L. lactis. Similar to S. mutans, expression of Cnm in L. lactis enabled robust binding to collagen and laminin, invasion of human coronary artery endothelial cells and increased virulence in G. mellonella. Using an ex vivo human heart tissue colonization model, we showed that Cnm-positive strains of either S. mutans or L. lactis outcompete their Cnm-negative counterparts for tissue colonization. Finally, Cnm expression facilitated L. lactis adhesion and colonization in a rabbit model of infective endocarditis. Collectively, our results provide unequivocal evidence that binding to extracellular matrices mediated by Cnm is an important virulence attribute of S. mutans and confirm the usefulness of the L. lactis heterologous system for further characterization of bacterial virulence factors.


Properties of cerebral polyribosomes and membranes of the rough endoplasmic reticulum after ethanol dependence in rats.
Effects of physical dependence upon ethanol on the polyribosomal properties and the reconstitution of the rough endoplasmic reticulum (RER) of the brain has been examined. The purified free polyribosomes (polysomes), membrane-bound polysomes, and a fraction of RER membrane that has been stripped of polysomes were isolated from rat brain. RNA yields, amino acid incorporation activities, and electron micrographs established the purity of stripped membranes, but no differences were detected following the ethanol treatment. For the polyribosomal fractions, the stability of the mRNA/ribosomal complex was decreased after ethanol dependence as was the in vitro translation of endogenous mRNA. In the reconstitution reaction, the incubation of membranes from ethanol-treated animals with either source of purified bound polysomes resulted in higher yields of protein than when control membranes were used. The above results suggest that ethanol dependence affects the properties of both the RNA and membrane components of the RER of brain.


Control of ovulation-induced hemoperitoneum by oral contraceptives in a patient with congenital hypoprothrombinemia and in another with congenital factor V deficiency.
Hemoperitoneum is a serious and often life-threatening bleeding manifestation. This is particularly true for women who carry congenital bleeding disorders. We describe here a hemoperitoneum occurring in 1 patient with congenital prothrombin deficiency and another with congenital factor V deficiency. Both patients have been followed by us for many years. The patient with prothrombin deficiency underwent laparoscopy but was treated consecutively with whole blood, plasma transfusions and 1,000 units of prothrombin complex concentrates. Response was good and she was then placed on oral contraceptives (OC) which prevented any recurrence. The patient with factor V deficiency presented several episodes of ovulation-related bleeding which required hospitalization and fresh frozen plasma transfusions. On the fifth occasion, the patient had to undergo surgery, and a left oophorectomy was carried out. After this last episode, she was also placed on OC which were very effective in preventing further recurrences. Both patients tolerated the medications very well which, in addition, were able to control menometrorrhagia with a consequent decrease over time in transfusional needs. OC are the treatment of choice in congenital bleeding disorders to control both the menorrhagia and, more importantly, ovulation-related hemoperitoneum.


Extracorporeal CPR and intra-aortic balloon pumping in tachycardia-induced cardiomyopathy complicating cardiac arrest.
Although tachycardia-induced cardiomyopathy (TIC) due to atrial fibrillation occurs frequently, it is under-recognized in clinical settings. TIC has a wide range of clinical manifestations, from asymptomatic tachycardia to cardiomyopathy leading to end stage heart failure. We present a case of a 48year-old-woman who presented as cardiogenic shock, and rapidly progressed to cardiac arrest from recently diagnosed but undertreated atrial fibrillation, resulting TIC in the emergency department (ED). She was rescued by extracorporeal cardiopulmonary resuscitation (E-CPR) for refractory cardiac arrest in the ED, and received concomitant intra-aortic balloon counterpulsation (IABP) support for severe left ventricular failure. Cardiogenic shock can present as an initial manifestation of TIC, and E-CPR and subsequent IABP support can be a valuable rescue therapy for severe TIC.


Chronic Obstructive Pulmonary Disease and Hepatitis C.
Chronic obstructive pulmonary disease (COPD) is a preventable, treatable disease with significant extrapulmonary manifestations that could affect negatively its course in some patients. Hepatitis C virus infection (HCV), on the other hand, is associated with a number of extrahepatic manifestations. COPD patients have increased prevalence of HCV and patients with HCV, especially older ones, have increased prevalence and faster progression of COPD. HCV infection exerts long-term effects on lung tissue and is an additional risk factor for the development of COPD. The presence of HCV is associated with an accelerated loss of lung function in COPD patients, especially in current smokers. COPD could represent extrahepatic manifestation associated with HCV infection. The aim of this article was to review the literature on prevalence of HCV in COPD and vice versa, pathogenetic link and the consequences of their mutual existence.


Quantifying the conceptual problems associated with the isotropic NICS through analyses of its underlying density.
The isotropic Nucleus Independent Chemical Shift (NICSiso) is widely considered to be a suitable descriptor for aromaticity based on the correlations it exhibits with other aromaticity descriptors. To gain more insight into the origin of these correlations, we establish causal relations between the NICSiso and the underlying current density patterns by resolving the NICSiso into its underlying density. Our results indicate that the origin of the behavior of the NICSiso can be radically different from what is generally assumed. Not only does this bring into question the robustness of applying the NICSiso beyond the realms of where good correlations with other measures of aromaticity have been established, it also points to an inherent weakness in all interpretations of NICSiso values that are not based on additional data.


[The guidelines for the diagnosis prevention and treatment of type 2 diabetes mellitus--2005].
The incidence and prevalence of diabetes have reached epidemic proportions worldwide. The reasons for the pandemic are the sharp rise in obesity, decline in physical activity and the increase in life expectancy. There are some 400,000 people with diagnosed diabetes in Israel and they are at a markedly increased risk for cardiovascular disease, blindness, end-stage renal disease and lower limb amputation. To effectively lower this significantly increased burden of disease, a comprehensive multidisciplinary approach to chronic disease management is required. To facilitate such an approach, the Israel Diabetes Association published a guideline for the diagnosis, prevention and treatment of diabetes. The guideline, based on the ADA (American Diabetes Association) and IDF (International Diabetes Federation) guidelines, was approved by other national professional societies including hypertension, family practice, obesity, nephrology, atherosclerosis and internal medicine. The guidelines highlight the metabolic syndrome and prediabetic states, interventions for the prevention of diabetes, the new definitions of diabetes and impaired glucose metabolism and the newly defined targets for glucose, lipid, cholesterol and blood pressure control. In addition, the recommendations for periodic review and screening for complications are summarized. The need for patient education and empowerment are emphasized as is the need for the development and implementation of unique tools including computerized treatment flow-charts, prompts and quality measures, for the long term management of a complex metabolic disease.


A Sampling-Based Approach for Achieving Desired Patterns of Probabilistic Coverage with Distributed Sensor Networks.
A new method is derived for finding the best positions in which to locate the sensors in a distributed sensor network in order to achieve a desired variation, or pattern, in spatial coverage over a specified domain. Such patterning is important in situations when there are not enough sensors to completely cover a region adequately. By providing coverage based on a desired pattern, this approach allows a user/designer to specify which sub-regions of the domain are more important to cover, and to what level that is desired. The method that is developed is novel in that it is an analytic approach, as opposed to existing numerical optimization approaches, and thus provides solutions rapidly and can also be applied to provide online repositioning for existing sensor networks to respond to changes in the environment. The method is based on deriving an expression for the probabilistic density of sensor locations that best matches the desired coverage under given spatially varying environmental conditions; and then samples from that sensor density to determine specific sensor locations. The performance of the method is demonstrated on numerical examples in both one-dimensional and two-dimensional settings. Comparisons are made between solutions found from this approach and solutions obtained by a numerical optimization technique.


Is p53 controlling spermatogenesis in male mice with the deletion on the Y chromosome?
The aim of the study was to evaluate the influence of the chromosome Y structure and Trp53 genotype on semen quality parameters. Mice with partial deletion of the Y chromosome (B10.BR-Ydel) have severely altered sperm head morphology when compared with males that possess the complete Y chromosome (B10.BR). Control males from B10.BR and B10.BR-Ydel mice, and mutant males from B10.BR-p53 -/- and B10.BR-Ydel-p53 -/- experimental groups were used. We assessed testis weight, sperm head abnormalities, viability of spermatozoa (eosin test), percentage of motile and immature sperm, and performed a hypo-osmotic test to detect abnormal tail membrane integrity. Sperm morphology and maturation were controlled by the genes within the deleted region of the Y chromosome. Testis weight was higher in the mutants than in the control males, possibly due to cell accumulation in Trp53-deficient males as the concentration of sperm was significantly increased in the mutants. An elevated percentage of abnormal sperm was noted in B10.BR-p53 -/- and B10.BR-Ydel-p53 -/- male mice. We suggest that, in Trp53-deficient mice, the sperm cells that escape apoptosis are the ones that have abnormal morphology. The only sperm quality parameter affected by the interplay between Trp53 and chromosome Y genes was sperm motility, which was elevated in B10.BR-p53 -/- males, but remained unchanged in B10.BR-Ydel-p53 -/- males.


Isolation of two distinct classes of polysomes from a nuclear fraction of rat liver.
Isolated rat liver nuclei were washed with Triton-X-100 in the presence of liver cell sap. This treatment liberated a fraction of polysomes which were isolated by differential centrifugation and were designated "outer membrane polysomes." The outer membrane polysomes synthesized protein in vivo. Shortly after injection of orotic acid-(14)C, the RNA of outer membrane polysomes had a higher specific activity than that of cytoplasmic polysomes. It was postulated that outer membrane polysomes may be an intermediate in the transfer of newly synthesized RNA from the nucleus to the cytoplasm. In other experiments, Triton-washed rat liver nuclei were lysed in the presence of deoxycholate and deoxyribonuclease. A ribonucleoprotein fraction was isolated from the lysate by differential centrifugation. This fraction contained "intranuclear ribosomes," which sedimented like partially degraded polysomes in sucrose gradients. This degradation could be partially prevented if intranuclear ribosomes were purified by sedimentation through heavy sucrose. The resulting pellets were termed "intranuclear polysomes" because they contained some undergraded polysomes. Intranuclear polysomes were highly radioactive after a brief pulse with orotic acid-(14)C, but did not appear to synthesize protein rapidly in vivo. Intranuclear polysomes may represent the initial stage of assembly of polyribosomes in the nucleus.


Epithelioid hemangioma of the temporal artery: a case report.
Temporal or giant cell arteritis is the most common vasculitis affecting the temporal artery. We encountered an unusual case of involvement of the temporal artery, which showed marked proliferating capillaries admixed with a dense infiltrate of eosinophils affecting all layers of the vessel. It was concluded that these changes were those of an epithelioid hemangioma of the temporal artery.


Hospital discharge summary scorecard: a quality improvement tool used in a tertiary hospital general medicine service.
We assessed the impact of completion and feedback of discharge summary scorecards on the quality of discharge summaries written by interns in a general medicine service of a tertiary hospital. The scorecards significantly improved summary quality in the first three rotations of the intern year and could be readily adopted by other units as a quality improvement intervention for optimizing clinical handover to primary care providers.


Potential Toxic Mechanisms of Neonicotinoid Insecticides in Rice: Inhibiting Auxin-Mediated Signal Transduction.
Inappropriate application of pesticides not only causes sub-lethal effects on ecosystem service providers but also reduces crop yield and quality. As a xenobiotic signal molecule, pesticides may interact with signal transduction receptors in crops, resulting in oxidative damage and even metabolic perturbations. We discovered that three neonicotinoid insecticides (NIs), namely, imidacloprid, thiamethoxam, and clothianidin, at 0.06-0.12 kg ai/ha significantly inhibited the auxin signal pathway in rice leaves, thereby reducing the intracellular auxin (IAA) content. Molecular simulation further confirmed that NIs occupied the binding site where auxin transporter-like proteins 1 (LAX11) and 2 (LAX12), in which Thr253 and Asn66 of LAX11, as well as Thr244 and Asn57 of LAX12, were bound to the nitroguanidine of NIs via H-bonds. Meanwhile, Asn66 of LAX11 and Asn57 of LAX12 interacted with nitroguanidine via aromatic H-bonds. Moreover, phenylpropanoid biosynthesis was significantly disturbed because of the inhibited auxin signal pathway. Notably, peroxidase-coding genes were downregulated with a maximum value greater than 10-fold, resulting in decreased antioxidant metabolites flavone (37.82%) and lignin content (20.15%). Ultimately, rice biomass was reduced by up to 25.41% due to the decline in IAA content and antioxidant capacity. This study deeply explored the molecular mechanism of metabolic perturbations in crops stressed by pesticides, thus providing a scientific basis for pesticide environmental risk assessment and agricultural product safety.


In-Depth Occlusion of Dentinal Tubules and Rapid Remineralization of Demineralized Dentin Induced by Polyelectrolyte-Calcium Complexes.
Dentin hypersensitivity (DH) is triggered by external stimuli irking fluid flow through exposed dentinal tubules (DTs). Three commercially available desensitizing agents as control in this study only achieve limited occlusion depths of ≈10 µm in the DTs as well as scarce remineralization of demineralized dentin matrix. Herein, polyelectrolyte-calcium complexes pre-precursor (PCCP) process is proposed for managing DH that demineralized dentin with exposed DTs is rubbed with ultrahighly concentrated polyelectrolyte-calcium suspension (4 g L-1 -5.44 m) followed by phosphate solution (3.25 m), each 10 min, leading to heavy remineralization of demineralized dentin and compact occlusion of the DTs over 200 µm after 1 day of in vitro and in vivo incubation. For the first time, it is demonstrated that the PCCP process relies on the pH-dependent electrostatic attraction between electropositive polyelectrolyte-calcium complexes and electronegative inwalls of DTs comprised of collagen fibrils and hydroxyapatite crystals under alkaline condition. The PCCP process might shed light on a promising dentin desensitizing strategy for DH management via rapid in-depth DT occlusion and remineralization of demineralized dentin.


P element insertion-dependent gene activation in the Drosophila eye.
Insights into the function of a gene can be gained in multiple ways, including loss-of-function phenotype, sequence similarity, expression pattern, and by the consequences of its misexpression. Analysis of the phenotypes produced by expression of a gene at an abnormal time, place, or level may provide clues to a gene's function when other approaches are not illuminating. Here we report that an eye-specific, enhancer-promoter present in the P element expression vector pGMR is able to drive high level expression in the eye of genes near the site of P element insertion. Cell fate determination, differentiation, proliferation, and death are essential for normal eye development. Thus the ability to carry out eye-specific misexpression of a significant fraction of genes in the genome, given the dispensability of the eye for viability and fertility of the adult, should provide a powerful approach for identifying regulators of these processes. To test this idea we carried out two overexpression screens for genes that function to regulate cell death. We screened for insertion-dependent dominant phenotypes in a wild-type background, and for dominant modifiers of a reaper overexpression-induced small eye phenotype. Multiple chromosomal loci were identified, including an insertion 5' to hid, a potent inducer of apoptosis, and insertions 5' to DIAP1, a cell death suppressor. To facilitate the cloning of genes near the P element insertion new misexpression vectors were created. A screen with one of these vectors identified eagle as a suppressor of a rough eye phenotype associated with overexpression of an activated Ras1 gene.


Role of exosomes in the development of the immune microenvironment in hepatocellular carcinoma.
Despite numerous improved treatment methods used in recent years, hepatocellular carcinoma (HCC) is still a disease with a high mortality rate. Many recent studies have shown that immunotherapy has great potential for cancer treatment. Exosomes play a significant role in negatively regulating the immune system in HCC. Understanding how these exosomes play a role in innate and adaptive immunity in HCC can significantly improve the immunotherapeutic effects on HCC. Further, engineered exosomes can deliver different drugs and RNA molecules to regulate the immune microenvironment of HCC by regulating the aforementioned immune pathway, thereby significantly improving the mortality rate of HCC. This study aimed to declare the role of exosomes in the development of the immune microenvironment in HCC and list engineered exosomes that could be used for clinical transformation therapy. These findings might be beneficial for clinical patients.


[Markers of thyroid function (II). Assessment of tissue action].
Advances in molecular medicine have increased our knowledge of the consequences of hormone action in target cells. We are currently able to determine to some extent the molecular thyroid hormone activity in different organs. The effects are related with a variety of factors, but their association with plasmatic hormone levels is only partially correlated. Recent advances indicate that there are several intermediate factors in thyroid tissue activity. The iodothyronine selenodeiodinases have a relevant role in this context. The clinical and biochemical methods currently available for thyroid function assessment do not permit us to explore many of these new elements. However, it is well known that thyroid hormones enhance the expression of a number of proteins, and some of these can be measured by simple methods. Accordingly, the plasmatic value of these proteins may be related with the effect of thyroid hormones in the target tissues, which is the result of thyroid function. The ability to determine the tissue activity of thyroid hormones will enable us to administrate the treatment dose more accurately, only to patients who require it, avoiding iatrogenism.


Shared learning for shared care.
This is an account of a pilot multidisciplinary course in geriatric care for medical, nursing and physiotherapy students at The Middlesex Hospital, London. The course organization, content and evaluation methods are described. A problem-solving approach to shared learning is discussed and the author argues for the development of similar teaching programmes.


Bead-based flow-cytometry for semi-quantitative analysis of complex membrane vesicle populations released by bacteria and host cells.
During infection, the release of nano-sized membrane vesicle is a process which is common both for bacteria and host cells. Host cell-derived membrane vesicles can be involved in innate and adaptive immunity whereas bacterial membrane vesicles can contribute to bacterial pathogenicity. To study the contribution of both membrane vesicle populations during infection is highly complicated as most vesicles fall within a similar size range of 30-300nm. Specialized techniques for purification are required and often no single technique complies on its own. Moreover, techniques for vesicle quantification are either complicated to use or do not distinguish between host cell-derived and bacterial membrane vesicle subpopulations. Here we demonstrate a bead-based platform that allows a semi-quantitatively analysis by flow-cytometry of bacterial and host-cell derived membrane vesicles. We show this method can be used to study heterogeneous and complex vesicle populations composed of bacterial and host-cell membrane vesicles. The easy accessible design of the protocol makes it also highly suitable for screening procedures to assess how intrinsic and environmental factors affect vesicle release.


A study of baker's yeast reduction of piperidone-carboxylates.
The stereoselective baker's yeast reduction of various N-protected piperidone-carboxylic acids have been studied, and the enantioselectivity was found to be widely dependent on whether fermenting or non-fermenting conditions were employed. Thus reaction of N-tert-butoxycarbonyl-4-oxopiperidine-3-carboxylic acid ethyl ester (6) with fermenting baker's yeast gave almost racemic N-tert-butoxycarbonyl-4-hydroxypiperidine-3-carboxylic acid ethyl ester (7), however, with complete diastereoselectivity. Reduction of 6 with non-fermenting yeast gave 7 with a 24-41% enantiomeric excess. Similarly, reduction of N-tert-butoxycarbonyl-3-oxopiperidine-4-carboxylic acid ethyl ester (17) with fermenting baker's yeast gave racemic N-tert-butoxycarbonyl-3-hydroxypiperidine-4-carboxylic acid ethyl ester [(+/-)-18] diastereoselectively. A convenient method for determining the enantiomeric excess of the hydroxypiperidine carboxylic acids derivatives was found in the reaction with Sanger's reagent followed by HPLC on a chiral column.


Dysregulation of the hypothalamic-pituitary-adrenal axis in postpartum depression.
Postpartum depression (PPD) affects at least 10% to 15% of postpartum women, including more than 600,000 American mothers in 2003 alone. Dramatic changes in the hypothalamic-pituitary-adrenal (HPA) system in the transition from pregnancy to postpartum coupled with research on the psychobiology of depression provided the foundation for this study. The purpose of this study was to compare the reactivity and regulation of the HPA axis components, adrenocorticotropic hormone (ACTH) and cortisol, in depressed and nondepressed postpartum women. A comparative, longitudinal study design was used with 22 normal, healthy, nondepressed pregnant women. Physiologic and postpartum depression data were collected at 6 and 12 weeks postpartum at a university clinical research center. Maximal treadmill exercise stimulated plasma ACTH and serum cortisol levels which were measured before, during, and after 20 min of exercise. Postpartum depression was measured with the Postpartum Depression Screening Scale. Lag within-subject ACTH levels predicting cortisol regression slopes were significantly different between the depressed and nondepressed groups at both 6 and 12 weeks. The depressed group showed no relationship between their ACTH and cortisol levels, with higher ACTH and lower cortisol levels when compared with the nondepressed group. The expected regulated relationship with cortisol levels rising in response to rising ACTH levels was found in the non-depressed group. These findings indicate that the HPA axis was dysregulated in the depressed group, but regulated in the nondepressed group at 6 and 12 weeks postpartum. This pattern of higher ACTH levels to stimulate less cortisol is similar to patterns found in women with early life stresses.


Effect of BDNF Val66Met and serotonin transporter 5-HTTLPR polymorphisms on psychopathological characteristics in a sample of university students.
The aims of this study were to evaluate the impact of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism on several psychological characteristics in a group of Greek University students and to explore putative interactions with the serotonin-transporter-linked polymorphic region (5-HTTLPR) and serious past adverse experiences. A total of 224 students were genotyped and classified as (a) carriers or noncarriers of the Met allele of the BDNF Val66Met polymorphism and (b) carriers or noncarriers of the S or Lg alleles (S') of the 5-HTTLPR polymorphism. Students were evaluated using a battery of standard psychological tests and answered questionnaires on serious past adverse experiences. The Val/Val BDNF genotype was associated with higher scores in several psychopathological dimensions. When the effect of the BDNF Met allele was examined in relation to 5-HTTLPR, it was restricted to S' noncarriers. Among these students, BDNF Met allele carriers had lower scores compared with noncarriers. The effects of the Met allele on the S' allele noncarriers in the anxiety and phobic anxiety dimensions were more pronounced among individuals who had reported no serious life adversities. There may be a protective role of the BDNF Met allele in several psychopathological features and it is suggested that some of these effects are moderated by 5-HTTLPR.


Goshajinkigan, a Traditional Japanese Medicine, Suppresses Voltage-Gated Sodium Channel Nav1.4 Currents in C2C12 Cells.
Goshajinkigan (GJG) is a traditional Japanese Kampo medicine used clinically to treat muscle pain in Japan. However, its underlying mechanism remains unclear. Since voltage-gated sodium channel (Nav) 1.4 is involved in skeletal muscle contraction, we investigated the possibility that GJG may affect Nav1.4 currents. By using an electrophysiological technique on skeletal muscle cell line C2C12, we found that GJG suppresses Nav1.4 currents in C2C12 cells. It is suggested that GJG may improve skeletal muscle stiffness or cramps by inhibiting abnormal Nav1.4 excitation. GJG may act as a Nav1.4 blocker and may be useful to treat muscle stiffness and clamps as well as easing the pain.


Binding analysis between L-histidine immobilized and oligonucleotides by SPR and NMR.
Saturation transfer difference (STD) NMR technique and surface plasmon resonance (SPR) are used to study amino acid affinity supports-nucleotides interactions with L-histidine amino acid immobilized on a surface as model support. We have immobilized L-histidine ligand on a carboxymethyldextran-modified gold surface intended for surface plasmon resonance and we analyze the binding profiles of synthetic polynucleotides (1-6 base, sugar and backbone) by determining the equilibrium dissociation constant (KD). The SPR binding profile (square-shaped) is identical for all the complexes and the highest binding affinity can be found for polyA₆ followed by polyG₆. As expected, the 5'-mononucleotides have the lowest affinity. To further study the structural aspects of the interaction we investigate the polynucleotide binding preferences to L-histidine chromatography support by STD-NMR spectroscopy. These results revealed that an increase in the number of bases and backbone to 6 units leads to more contacts with the support, where the main driving force for the interaction with polynucleotides are through the base, except for polyC₆, which is mainly through sugar-phosphate backbone. Therefore, the combination of SPR measurements with STD-NMR technique allowed to establish fine details of the molecular recognition process involved in amino acid affinity supports-nucleotides complexes.


The effects of fibroblast growth factor-2 on human neonatal calvaria osteoblastic cells are differentiation stage specific.
Fibroblast growth factors (FGFs) appear to play an important role in human cranial osteogenesis. We therefore investigated the effects of recombinant human FGF-2 (rhFGF-2) on human calvaria (HC) osteoblastic cells. Immunocytochemical analysis showed that confluent HC cells express both FGF receptors -1 and -2. In short-term culture, rhFGF-2 (0.1-100 ng/ml, 2-5 days) increased HC cell growth and decreased alkaline phosphatase (ALP) activity and type I collagen (ColI) synthesis, as evaluated by P1CP levels. When HC cells were induced to differentiate in long-term culture in the presence of 50 microg/ml ascorbic acid and 3 mM phosphate, HC cells initially proliferated, then ALP activity and ColI synthesis decreased and calcium content in the extracellular matrix increased. Continuous treatment with rhFGF-2 (50 ng/ml) for 1-28 days, or a transient rhFGF-2 treatment for 1-7 days, slightly increased DNA synthesis at 7 days, whereas a late treatment for 8-28 days had no effect on cell growth. The continuous and transient treatments with rhFGF-2 decreased ALP activity, ColI synthesis, and matrix mineralization. This was associated with a transient fall in osteocalcin (OC) production at 7 days. In contrast, the late rhFGF-2 treatment for 8-28 days only slightly inhibited ALP activity and increased matrix mineralization. In addition, both continuous and late treatments with rhFGF-2 increased OC production in more mature cells at 3-4 weeks of culture. We also found that the early and late treatments with rhFGF-2 had opposite effects on transforming growth factor beta2 production in proliferating cells and more mature cells. The results show that rhFGF-2 slightly stimulates cell growth and reduces the expression of osteoblast markers in less mature cells, whereas it induces OC production and matrix mineralization in more mature cells, indicating that the effects of FGF-2 are differentiation stage specific and that FGF-2 may modulate HC osteogenesis by acting at distinct stages of cell maturation.


The patient as sufferer.
The use of the term sufferer to replace patient has become increasingly common. This paper examines the varied meanings implicit in the word sufferer from the Judaeo-Christian perspective. This includes the biblical themes of suffering as human nature, as punishment, as a test, as atonement and as liberation and deliverance. The consequences of these themes for the sufferer's role are examined, particularly the sufferer as accepting and the sufferer as victim. It is argued that replacing the medical model, implied by 'patient' with a theological model, implied by 'sufferer' does not free the person from the constraints of a damaging label.


Propulsion optimization of a jellyfish-inspired robot based on a nonintrusive reduced-order model with proper orthogonal decomposition.
In this research, the propulsion of the proposed jellyfish-inspired mantle undulated propulsion robot (MUPRo) is optimized. To reliably predict the hydrodynamic forces acting on the robot, the proposed nonintrusive reduced-order model (NIROM) based on proper orthogonal decomposition (POD) additionally considers the POD basis that makes an important contribution to the features on the specified boundary. The proposed model establishes a mapping between the parameter-driven motion of the mantle and the evolution of the fluid characteristics around the swimmer. Moreover, to predict new cases where the input needs to be updated, the input of the proposed model is taken from the kinematics of the robot rather than extracted from full-order high-fidelity models. In this paper, it takes approximately 950 s to perform a simulation using the full-order high-fidelity model. However, the computational cost for one prediction with the proposed POD-NIROM is around 0.54 s, of which about 0.2 s is contributed by preprocessing. Compared with the NIROM based on the classic POD method, the proposed POD-NIROM can effectively update the input and reasonably predict the characteristics on the boundary. The analysis of the hydrodynamic performance of the MUPRo pinpoints that, over a certain period and with a certain undulation amplitude, the hydrodynamic force generated by the swinging-like mantle motion (k< 0.5) is greater, outperformingAequorea victoriain startup acceleration. It is demonstrated that considering a certain power loss and a certain tail beat amplitude, the wave-like mantle motion (k> 0.5) can produce greater propulsion, which means higher propulsion efficiency.


Characterization of a programmed alteration in an 18S ribosomal gene that accompanies the experimental induction of drug resistance in Schistosoma mansoni.
Stable resistance to the anthelmintic hycanthone can be produced in the human blood fluke Schistosoma mansoni by exposing immature parasites in mice to the drug. Within a single generation, genomic rearrangements, detected as rRNA-encoding DNA restriction fragment length polymorphisms (RFLPs), accompany the appearance of resistance in this model. One of these RFLPs, an approximately 3.6-kilobase BamHI fragment, was shown previously to associate consistently with resistance in independent generations of the JHU strain of S. mansoni. To characterize the genetic changes responsible for this RFLP, the fragment was cloned and sequenced. A comparison of the cloned fragment with a normal 18S rRNA gene demonstrated that the drug resistance-associated RFLP fragment arises through the addition of 732 base pairs into an 18S rRNA gene, 134 base pairs downstream of the junction of the intergenic spacer and the mature 18S rRNA gene. The mutation is nonrandom, targets one, or a few only, of the 100 or so copies of the ribosomal genes, and may represent the incomplete duplication of the gene since the inserted element is identical in sequence to the region contiguous to it. The sequence spanning the junction of the insertion and the original 18S rRNA gene was used as a specific primer for the BamHI RFLP in PCR experiments. The analysis conclusively demonstrated that the mutation is induced rather than selected by the drug since the junctional sequence was not detectable in the drug-sensitive parent population of schistosomes. In addition, analysis of four, independently derived, resistant lines indicated that the same region of the gene was mutated each time. Together, these data demonstrate that reproducible changes are induced during the acquisition of resistance in schistosomes and suggest that the resistant phenotype is induced rather than selected from preexisting forms.


Vibrometry: a novel noninvasive application of ultrasonographic physics to estimate wall stress in native aneurysms.
Our objective was to test vibrometry as a means to measure changes in aneurysm sac pressure in an in vitro aneurysm model. Explanted porcine abdominal aortas and nitrile rubber tubes were used to model an aneurysm sac. An ultrasound beam was used to vibrate the surface of the aneurysm model. The motion generated on the surface was detected either by reflected laser light or by a second ultrasound probe. This was recorded at different aneurysm pressures. The phase of the propagating wave was measured to assess changes in velocity and to see if there was a correlation with aneurysm pressure. The cumulative phase shift detected by laser or Doppler correlated well with increasing hydrostatic pressure in both the rubber and the porcine aorta model. The square of the mean pressure correlated well with the cumulative phase shift when dynamic pressure was generated by a pump. However, the pulse pressure was poorly correlated with the cumulative phase shift. Noninvasive measurement of changes in aortic aneurysm sac tension is feasible in an in vitro setting using the concept of vibrometry. This could potentially be used to noninvasively detect wall stress in native aneurysms and endotension after endovascular aneurysm repair (EVAR) and to predict the risk of rupture.


Associated anomalies and clinical outcome in children with ectopic kidney.
Urological anomalies can be seen in children with renal ectopia (RE) and can result in renal impairment. Therefore, we evaluated associated anomalies and renal outcome in our patients with RE. Sixty-eight children who were diagnosed with RE between January 2009-May 2014 were retrospectively studied. A total of 68 patients, 36 (52.9%) boys, with a median age of 67 months (4-201) and a median follow-up period of 14 months (3-113) were included in the study. Simple RE (S-RE) was found in 51 (75%) patients, of which 46 were unilateral and five were bilateral (discoid kidney). Crossed RE (C-RE) was detected in 17 (25%) patients. Voiding cystourethrogram was performed in 21/51 (41.2%) patients in S-RE group and 5/17 (29.4%) in C-RE group. We did not find vesicoureteral reflux (VUR) in any of the patients with C-RE, whereas, in S-RE group, VUR was demonstrated in six (6/21 - 28.6%) patients. Pelviureteric junction obstruction in ectopic kidney was found in two patients with S-RE and one with C-RE. Two patients (2/17 - 11.7%) had neurogenic bladder due to meningomyelocele, accompanied by imperforate anus in C-RE group. There were no significant differences in other associated urological anomalies between two groups. Renal impairment developed mostly in patients with additional urinary anomaly. The children with RE may have associated urinary anomalies, of which VUR is the most common. Complete urological investigation and regular follow-up are required in selected cases.


EFFECTS OF A SEASON OF SUBCONCUSSIVE CONTACT ON CHILD- SCAT3 SCORES IN 8-12 YEAR-OLD MALE ATHLETES.
Each year, over 173,000 children and adolescents visit emergency departments due to sports and recreation related concussions, an increase of 60% over the last decade due to the rise in the number of children participating in sport. While numerous authors have sought to address the epidemiology of concussions across multiple age groups who participate in contact sports, a recent review of literature did not reveal a substantial amount of published articles that addressed the issue of subconcussive contact. Multiple tools have been developed to assess acute episodes of concussion. Among the assessment protocols many include an assessment of balance, short and long term memory recall, and balance. The Child-SCAT3 was designed specifically to evaluate concussions in children 5-12 years of age. The purpose of this study was to determine the effect of a season of subconcussive contact on Child-SCAT3 scores in 8-12 year old males compared to their age matched peers who participated in non-contact sports. A secondary purpose was to evaluate how scores of the sub- components of the Child-SCAT3 compare between contact and non-contact athletes. A prospective cohort study was performed of 71 male athletes (58 football, 13 baseball) ages 8-12 (contact mean age 10.30 years, SD 1.20; non-contact mean age 10.03 years, SD 1.26) over the course of a season. Portions of The Child-SCAT3 were administered and scored in pre-adolescent athletes prior to and following a season of participation in football (contact sport group) and baseball (non-contact sport group). The outcome measures of interest included the portions related to Cognitive ability, Balance, and Coordination. No statistically significant differences were found in group, time or time and group interaction for any of the utilized portions of the Child-SCAT3. Statistically significant differences were found between groups for preseason cognitive orientation and postseason immediate memory. Cognitive orientation and coordination were also found to be statistically significantly improved across both groups over the course of the season. This study was potentially limited by the number of control subjects tested. A season of subconcussive contact in football was not detrimental to cognitive and balance scores on the Child-SCAT3. 3.


Assessment and treatment options for patients with constipation.
Constipation is a common complaint for people of all ages, with prevalence increasing with age and during pregnancy. Women are more likely to be affected than men. Severity of constipation varies from person to person; most people experience short periods of constipation during their lives, including possibly after surgery, while others have constipation as a chronic long-term condition that can significantly affect their quality of life. There are a number of factors that can contribute to developing constipation including diets low in fibre, changes in lifestyle, side effects of certain medications and low fluid intake. People can successfully treat constipation by making changes to their diet and lifestyle. However, medication may be required to manage constipation for some.


Experimental demonstration of an intensity minimum at the focus of a laser beam created by spatial coherence: application to the optical trapping of dielectric particles.
In trying to manipulate the intensity distribution of a focused field, one typically uses amplitude or phase masks. Here we explore an approach, namely, varying the state of spatial coherence of the incident field. We experimentally demonstrate that the focusing of a Bessel-correlated beam produces an intensity minimum at the geometric focus rather than a maximum. By varying the spatial coherence width of the field, which can be achieved by merely changing the size of an iris, it is possible to change this minimum into a maximum in a continuous manner. This method can be used, for example, in novel optical trapping schemes, to selectively manipulate particles with either a low or high index of refraction.


Carcinoma in a bladder diverticulum: presentation and treatment outcome.
In this retrospective review we characterize the outcomes of patients treated for transitional cell carcinoma in a bladder diverticulum. Between 1986 and 2001, 39 patients were treated for tumors in a bladder diverticulum. All patients underwent initial transurethral resection of the tumor. Based on cystoscopic evaluation, bimanual examination and computerized tomography findings, tumors were classified as superficial (Ta, Tis), superficially invasive confined to diverticulum (T1) or extra diverticular (T3+). Patients with superficial or superficially invasive disease were treated either conservatively with repeat transurethral resection, or with partial or radical cystectomy. Patients with extra diverticular extension were treated with partial or radical cystectomy when amenable to surgical extirpation. Predictors of outcome were assessed by univariate and multivariate analyses. End point was overall and disease-specific survival. Of our cohort of 39 patients 13 (33%) presented with superficial disease, 13 (33%) with superficially invasive tumors and 13 (33%) with invasive (extra diverticular) disease. Actuarial 5-year disease specific survival for the cohort was 72 +/- 5.4%. Significant differences in 5-year disease specific survival were observed among patients presenting with superficial tumors (83 +/- 9%), superficially invasive tumors (67 +/- 7%) and extra diverticular disease (45 +/- 14%). Of the patients presenting with T1 tumors the primary mode of treatment did not correlate with outcome. In a multivariate model clinical staging was the only independent predictor of outcome and concomitant carcinoma in situ reached borderline significance. Our data support a conservative approach for tumors confined to the bladder diverticulum, provided complete removal is feasible and close surveillance ensues.


Testing mediators of intervention effects in randomized controlled trials: An evaluation of three depression prevention programs.
Evaluate a new 5-step method for testing mediators hypothesized to account for the effects of depression prevention programs. In this indicated prevention trial, at-risk teens with elevated depressive symptoms were randomized to a group cognitive-behavioral (CB) intervention, group supportive expressive intervention, CB bibliotherapy, or assessment-only control condition. The group CB intervention reduced depressive symptoms and negative cognitions and increased pleasant activities. Change in these mediators predicted change in depression, and intervention effects became weaker controlling for change in the mediators; yet, change in depression appeared typically to occur before change in the mediators. The supportive expressive intervention reduced depressive symptoms but affected only 1 of 2 mediators (emotional expression but not loneliness). Change in emotional expression did not correlate with change in depression, and change in depression usually occurred before change in the mediators. Bibliotherapy did not significantly affect depressive symptoms or the ostensive mediators (negative cognitions and pleasant activities), and change in depression usually occurred before change in the mediators. Results imply that this procedure provides a sensitive test of mediation but yielded limited support for the hypothesized mediators, suggesting that nonspecific factors may play an important mediational role.


Effects of interaural decoherence on sensitivity to interaural level differences across frequency.
The interaural level difference (ILD) is a robust indicator of sound source azimuth, and human ILD sensitivity persists under conditions that degrade normally-dominant interaural time difference (ITD) cues. Nonetheless, ILD sensitivity varies somewhat with both stimulus frequency and interaural correlation (coherence). To further investigate the combined binaural perceptual influence of these variables, the present study assessed ILD sensitivity at frequencies 250-4000 Hz using stimuli of varied interaural correlation. In the first of two experiments, ILD discrimination thresholds were modestly elevated, and subjective lateralization slightly reduced, for both half-correlated and uncorrelated narrowband noise tokens relative to correlated tokens. Different from thresholds in the correlated condition, which were worst at 1000 Hz [Grantham, D.W. (1984). J. Acoust. Soc. Am. 75, 1191-1194], thresholds in the decorrelated conditions were independent of frequency. However, intrinsic envelope fluctuations in narrowband stimuli caused moment-to-moment variation of the nominal ILD, complicating interpretation of measured thresholds. Thus, a second experiment employed low-fluctuation noise tokens, revealing a clear effect of interaural decoherence per se that was strongly frequency-dependent, decreasing in magnitude from low to high frequencies. Measurements are consistent with known integration times in ILD-sensitive neurons and also suggest persistent influences of covert ITD cues in putative "ILD" tasks.


The experience of self for women who are mothers. Implications for the unfolding of health.
Although the expression and transformation of self is integral to people's health and healing experiences, nurses currently lack an in-depth understanding of how women who are mothers experience and express themselves. This article presents the results of a recent study that examined the lived experience of self for mothers. Principles of interpretive phenomenology and feminist inquiry guided the investigation. The results of the study describe the nature and experience of self for the 7 women/mother participants and highlight the complementary relationship between the experience of oneself and the unfolding of health. Three essential themes emerged to describe the experience of self, including (a) self as a multiplicity of parts, (b) self as a relational process, and (c) self as a synthesis. The results illustrate the complementary relationship between health and self experience and highlight the nursing imperative of supporting women/mothers in their unfolding of self.


7 steps for evaluating primary care practice ownership.
Hospitals shouldn't dismiss a primary care practice ownership strategy from the outset. Instead, it's important to learn from past missteps and conduct a thorough analysis of the opportunity by focusing on population growth and demographics, hospital utilization rates, disease and illness rates, physician supply and demand, market share, case-mix index, other hospital-owned physician practices, and concerns pertinent to the potential development site.


Intravenous regional analgesia. The danger of the congested arm and the value of occlusion pressure.
Two cases are described in which congestion of the arm occurred during intravenous regional analgesia. One case exhibited signs of serious local anaesthetic toxicity, while a significant plasma bupivacaine level was demonstrated in the other. In a study in a volunteer, leakage of contrast medium past the cuff was demonstrated radiologically only when congestion of the arm was produced. The Hoyle double cuff apparatus has narrow cuffs producing less tissue compression than a standard blood pressure cuff inflated to the same pressure. It may sometimes not occlude the brachial artery when inflated to a pressure based on the systolic arterial pressure measured with a standard cuff and congestion of the arm may then result. Increases in arterial blood pressure occurring during the procedure can also lead to congestion of the arm. Congestion may increase the risk of local anaesthetic agent leaking past the tourniquet into the systemic circulation. Recommendations are made about the choice of cuff gauge pressure and the prevention of arm congestion occurring during intravenous regional analgesia.


Acute suicidal self-poisonings during pregnancy.
Selected clinical aspects of suicidal attempts during pregnancy were presented. Nineteen pregnant females, in the age range 17-27 (mean 22 +/- 2.58), were admitted to the Clinic of Acute Poisonings in Gdańsk and Toxicological Ward in Poznań between 2001 and 2004 because of acute suicidal intoxication. The main attention was put on reasons of self-intoxication, the timing of attempted suicide as well as the influence of intoxication on the mother and the child. For most admitted women it was their first pregnancy (12 cases, 63.2%). The week of pregnancy varied from 4 to 37 (mean 19 +/- 9.3) weeks. The most popular drugs for attempting suicide among pregnant females were benzodiazepines (7 cases, 36.8%). The most often reason of suicidal attempts was unplanned pregnancy (9 cases, 47.4%). There were two miscarriages and one premature birth observed in our cases. Acute self-poisonings during pregnancy appeared to be a relatively marginal problem in the analyzed toxicology clinics and occurred in merely 0.38% of all women hospitalized between 2001 and 2004 in both clinics. The main reason of suicidal attempts in pregnant women was unplanned pregnancy (9 cases, 47.4%). None of the studied females admitted that the main reason of suicidal attempt was an abortion induction.


The diversity of the N2O reducers matters for the N2O:N2 denitrification end-product ratio across an annual and a perennial cropping system.
Agriculture is the main source of terrestrial emissions of N2O, a potent greenhouse gas and the main cause of ozone layer depletion. The reduction of N2O into N2 by microorganisms carrying the nitrous oxide reductase gene (nosZ) is the only biological process known to eliminate this greenhouse gas. Recent studies showed that a previously unknown clade of N2O-reducers was related to the capacity of the soil to act as an N2O sink, opening the way for new strategies to mitigate emissions. Here, we investigated whether the agricultural practices could differently influence the two N2O reducer clades with consequences for denitrification end-products. The abundance of N2O-reducers and producers was quantified by real-time PCR, and the diversity of both nosZ clades was determined by 454 pyrosequencing. Potential N2O production and potential denitrification activity were used to calculate the denitrification gaseous end-product ratio. Overall, the results showed limited differences between management practices but there were significant differences between cropping systems in both the abundance and structure of the nosZII community, as well as in the [rN2O/r(N2O+N2)] ratio. More limited differences were observed in the nosZI community, suggesting that the newly identified nosZII clade is more sensitive than nosZI to environmental changes. Potential denitrification activity and potential N2O production were explained mainly by the soil properties while the diversity of the nosZII clade on its own explained 26% of the denitrification end-product ratio, which highlights the importance of understanding the ecology of this newly identified clade of N2O reducers for mitigation strategies.


Synthesis of a donor-acceptor diblock copolymer via two mechanistically distinct, sequential polymerizations using a single catalyst.
Treatment of a Ni-terminated poly(3-hexylthiophene) (P3HT), generated in situ from 5-chloromagnesio-2-bromo-3-hexylthiophene and Ni(1,3-bis(diphenylphosphino)propane)Cl2, with a perylene diimide-functionalized arylisocyanide monomer effects a chain-extension polymerization to afford a donor-acceptor diblock copolymer using a single catalyst and in a single reaction vessel. The two mechanistically distinct polymerizations proceed in a controlled, chain growth fashion, allowing the molecular weight of both the P3HT and poly(isocyanide) blocks to be tuned by adjusting the initial monomer-to-catalyst ratios. The resulting materials are found to self-assemble into crystalline, lamellar stacks of donor and acceptor components in the solid state, and also exhibit fluorescence quenching in thin films, properties which poise these materials for use in organic photovoltaic applications.


In vivo studies on non-viral transdifferentiation of liver cells towards pancreatic β cells.
Transdifferentiation in vivo is an attractive option for autologous replacement of pancreatic β cells in patients with type 1 diabetes. It has been achieved by adenoviral delivery of genes for transcription factors in the liver and pancreas of hyperglycaemic mice. However, these viral approaches are not clinically applicable. We used the hydrodynamic approach to deliver genes Pdx1, Ngn3 (Neurog3) and MafA singly and in combination to livers of normoglycaemic rats. Five expression plasmids were evaluated. Livers were removed 1, 3, 7, 14 and 28 days after gene delivery and assayed by quantitative PCR, semi-quantitative PCR and immunohistology. Functional studies on hyperglycaemic rats were performed. The highest and most sustained expression was from a CpG-depleted plasmid (pCpG) and a plasmid with an in-frame scaffold/matrix attachment region ((pEPI(CMV)). When Pdx1, Ngn3 and MafA were delivered together to normoglycaemic rats with these plasmids, insulin mRNA was detected at all time points and was ~50-fold higher with pCpG. Insulin mRNA content of livers at days 3 and 7 was equivalent to that of a pancreas, with scattered insulin-positive cells detected by immunohistology, but levels declined thereafter. Prohormone convertase 1/3 was elevated at days 3 and 7. In hyperglycaemic rats, fasting blood glucose was lower at days 1, 3 and 7 but not thereafter, and body weight was maintained to day 28. We conclude that hydrodynamic gene delivery of multiple transcription factors to rat liver can initiate transdifferentiation to pancreatic β cells, but the process is reversible and probably requires more sustained transcription factor expression.


Spectral CT imaging of vulnerable plaque with two independent biomarkers.
The purpose of this paper is to investigate the feasibility of a novel four-material decomposition technique for assessing the vulnerability of plaque with two contrast materials spectral computer tomography (CT) using two independent markers: plaque's inflammation and spotty calcification. A simulation study was conducted using an energy-sensitive photon-counting detector for k-edge imaging of the coronary arteries. In addition to detecting the inflammation status, which is known as a biological marker of a plaque's vulnerability, we use spotty calcium concentration as an independent marker to test a plaque's vulnerability. We have introduced a new method for detecting and quantifying calcium concentrations in the presence of two contrast materials (iodine and gold), calcium and soft tissue background. In this method, four-material decomposition was performed on a pixel-by-pixel basis, assuming there was an arbitrary mixture of materials in the voxel. The concentrations of iodine and gold were determined by the k-edge material decomposition based on the maximum likelihood method. The calibration curves of the attenuation coefficients, with respect to the concentrations of different materials, were used to separate the calcium signal from both contrast materials and different soft tissues in the mixtures. Three different materials (muscle, blood and lipid) were independently used as soft tissue. The simulations included both ideal and more realistic energy resolving detectors to measure the polychromatic photon spectrum in single slice parallel beam geometry. The ideal detector was used together with a 3 cm diameter digital phantom to demonstrate the decomposition method while a more realistic detector and a 33 × 24 cm(2) digital chest phantom were simulated to validate the vulnerability assessment technique. A 120 kVp spectrum was generated to produce photon flux sufficient for detecting contrast materials above the k-edges of iodine (33.2 keV) and gold (80.7 keV). By performing simulations on a 3 cm diameter digital phantom, we successfully identified four materials that were simultaneously present in the mixture at different proportions and in multiple locations on the phantom. Quantitative analysis with a chest digital phantom showed that the results for iodine, gold and calcium were highly correlated with the known concentrations. The analysis revealed a potentially powerful technique for assessing a plaque's vulnerability with two independent markers. High correlation and low relative errors between calculated and known materials' concentrations showed that the method is feasible. This technique can potentially have a high clinical impact.


Identification of gram positive cocci isolated from urine.
A total of 195 strains of Gram positive cocci isolated from urine, in pure culture and in counts of > 10(3) colony forming units/ml, during January-September 1992, were speciated using schema recently described by Facklam and Washington, and Kloos and Lambe. Seventy three (85%) of the 86 enterococci were identified as Enterococcus faecalis while 11 (13%) were E. faecium. Eighteen (29%) of the 62 staphylococcal isolates were Staphylococcus aureus; 20 (45%) of the 44 coagulase negative staphylococci were speciated as Staph. haemolyticus. Of the 47 strains of beta haemolytic streptococci isolated, 45 (96%) were group B; one was group G and the other group F. Our results show the diverse species of Gram positive cocci associated with bacteriuria and the need to speciate them in a diagnostic laboratory. In the context of a larger number of tests required for the speciation of Gram positive cocci, we recommend a simplified scheme which we found feasible on a routine basis.


Expression of somatic DNA repair genes in human testes.
Meiosis is the key process for recombination and reduction of the diploid chromosome set to a haploid one. Many genes that have been found in yeast or mouse models to play a role in meiosis are also important for the repair of DNA damage in somatic cells. To study the DNA repair gene transcriptome during male germ cell development, we have developed a specialized cDNA microarray with 181 human genes which are involved in different somatic DNA repair pathways and/or cell cycle control and 45 control house-keeping genes. This DNA repair gene chip was used to quantify the mRNA expression levels in three human testes samples versus a fibroblast RNA pool. Two hundred twenty genes on the chip (including house-keeping genes) showed detectable expression levels in adult testes. Sixty-four DNA repair- and cell cycle-associated genes showed higher expression levels in testicular cells than in mitotically dividing fibroblasts and, therefore, are likely to be implicated in meiosis. The microarray results of 17 genes with increased expression levels were validated with reverse Northern blots or real-time quantitative RT PCR. Systematic analyses of the meiotic DNA repair gene transcriptome may provide new insights into the genetics of male (in)fertility.


Increased anti-oxidant enzyme activity and biological oxidation in placentae of pregnancies complicated by maternal asthma.
Our previous work has demonstrated that alterations in placental function are associated with changes in fetal development in pregnancies complicated by asthma. The pathophysiology of asthma in adults and children and intrauterine growth restriction during pregnancy are associated with oxidative stress. Based on this information, we examined whether placental anti-oxidant pathways and markers of biological oxidation were altered in pregnancies complicated by asthma. Anti-oxidant enzyme activities of superoxide dismutase, glutathione peroxidase and thioredoxin reductase, thioredoxin concentrations, lipid and protein oxidation levels were measured in placentae of pregnancies complicated by asthma and compared to uncomplicated, non-asthmatic pregnancies. Placental tissue homogenates of pregnancies complicated by asthma demonstrated significantly increased levels of lipid peroxidation (25.7+/-1.8 micromol/mg protein versus 12.1+/-1.6 micromol/mg protein, P=0.008) and protein carbonyl concentrations (414.6+/-51.4 units/mg protein versus 222.3+/-32.6 units/mg protein, P=0.0032) when compared to non-asthmatic controls. The activities of the anti-oxidant proteins superoxide dismutase (2.17+/-0.09 units/mg protein versus 1.67+/-0.09 units/mg protein, P=0.014) and thioredoxin reductase (54.0+/-6.9 units/mg protein versus 28.7+/-6.0 units/mg protein, P=0.009) were significantly increased in the presence of maternal asthma. Placental thioredoxin levels (102.9+/-5.3 ng/mg protein versus 92.9+/-8.6 ng/mg protein, P=0.37) and glutathione peroxidase activity (27.3+/-2.2 mmol/min/mg protein versus 28.3+/-2.2 mmol/min/mg, P=0.83) were not significantly different in pregnancies complicated by asthma and non-asthmatic pregnancies. There was no effect of fetal sex, asthma severity or treatment for asthma on these pathways. Maternal asthma during pregnancy is associated with increased placental enzymatic anti-oxidant capacity and also increased protein oxidation suggesting there is a compensatory increase in anti-oxidant activity in response to increased oxidative stress.


Serpina3n, Dominantly Expressed in Female Osteoblasts, Suppresses the Phenotypes of Differentiated Osteoblasts in Mice.
It is well known that sex differences exist concerning the severity of osteoporosis and bone metabolism, suggesting that factors other than sex hormones might be responsible for sex differences of bone metabolism. We therefore examined sex differences of osteoblast phenotypes of mouse osteoblasts and then performed comparative gene expression analyses using a comprehensive DNA microarray between female and male osteoblasts. Alkaline phosphatase (ALP) activity, mineralization, and the expression of Osterix, ALP, and bone sialoprotein were significantly lower in mouse female osteoblasts compared with male osteoblasts. We identified Serpina3n, a novel serine protease inhibitor, as the gene whose expression has the highest ratio of females to males. A reduction in endogenous levels of Serpina3n by small interfering RNA significantly enhanced the mRNA levels of Runx2, ALP, osteocalcin, and type I collagen (Col1a1) in both male and female osteoblasts. Moreover, Serpina3n overexpression significantly suppressed the mRNA levels of Osterix, ALP, osteocalcin, and Col1a1 in MC3T3-E1 cells. Serpina3n overexpression did not affect Osterix, ALP, and osteocalcin mRNA levels enhanced by bone morphogenetic protein (BMP)-2 in ST2 cells, adipogenic differentiation in ST2 and 3T3-L1 cells, and receptor activator of nuclear factor κB ligand-induced osteoclast formation in RAW264.7 cells, although it significantly suppressed mineralization in ST2 cells differentiated into osteoblasts by BMP-2. In conclusion, we found Serpina3n as the most female osteoblast-dominant gene. Serpina3n exerts a suppression of the osteoblast phenotypes such as Col1a1 expression and ALP activity in differentiated osteoblasts, which might partly explain sex differences of the osteoblast phenotypes in mice.


Stem cell transplantation for severe autoimmune disorders, with special reference to rheumatic diseases.
Animal models of autoimmune disease have been successfully used to explore peripheral stem cell transfusion and bone marrow transplantation. Allogeneic marrow transplants have been shown to suppress lupus-like disease and experimental allergic encephalomyelitis. Autologous transplantation has also been successful in adjuvant arthritis. Operationally, these may be considered as graft versus autoimmunity effects. In humans, adoptive autoimmunity, in which the donor becomes apparent in the recipient, has been documented for myasthenia gravis and insulin dependent diabetes mellitus. Of 9 allogeneic bone marrow transplants for rheumatoid arthritis, 4 patients have done well for many years while one relapsed after 2 years. In 2 cases, autologous marrow transplant has been used specifically to treat autoimmune disease: one patient with CREST had only a transient response and one patient with myasthenia gravis had remission. While allogeneic bone marrow transplant is the most rational procedure, its use in nonmalignant disorders must be very carefully considered secondary to its toxicity and potential morbidity. The use of peripheral blood CD34+ cells with T cell depletion, may promise complete or partial longterm remission but results of this therapy need to be compared with other immunosuppressive combinations.


Operative procedure and volumetry in experimental biomechanical hearts.
To date, skeletal muscle ventricles (SMVs) have been integrated into the circulation by a second operation following construction, vascular delay and several weeks of electrical conditioning. Recently, intra-thoracic SMVs around a mock system contracted against a pressure of 70 mmHg for several months immediately after construction in the presence of clenbuterol. This indicates that the two-step procedure may be exchanged for a clinically favorable one-step operation. The stroke volume is tested intra-operatively. In twelve Boer goats, the latissimus dorsi muscle was folded in a double layer around a polyurethane chamber, which was integrated into descending thoracic aorta. This muscular flow-through chamber containing a stabilizing inner layer denoted "Biomechanical Heart" (BMH) showed immediate activity against systemic pressure. The conductance catheter method was applied for analysis of intra-operative stroke volume. The one-step operative procedure employed was practicable in all 12 goats. Operative complications were eliminated without difficulty. Intraoperative application of the conductance catheter resulted in BMH with a stroke volume of 55 +/- 14 ml. In the best BMH on postoperative day 132, a continuous pumping capacity of 1.4 l/min was measured. This BMH functioned up to day 414 postoperatively, and failed due to a rupture of the pumping chamber. This operative procedure and dynamic volumetry of experimental Biomechanical Hearts might be relevant for clinical use.


Critical Application of Adult Nephrolithometric Scoring Systems to Children Undergoing Mini-Percutaneous Nephrolithotomy.
Objective: To evaluate and compare the ability of the Guy's stone score (GSS), the S.T.O.N.E. nephrolithometry, and the Clinical Research Office of the Endourology Society (CROES) nomogram to predict the outcome of mini-percutaneous nephrolithotomy (MPNL) in children, and to identify which of the predictors involved in these scoring systems can separately affect this outcome. Patients and Methods: All children younger than 14 years who had MPNL in our center over a period of 3 years were included prospectively. Bivariate analyses were done to evaluate the associations of the three scoring systems and the predictors composing them with single-session stone clearance and complications. Receiver operating characteristic (ROC) curve analyses of the three scoring systems were conducted to evaluate and compare their abilities to predict the outcomes. Decision curve analyses for the three scoring systems were conducted to evaluate the clinical benefit of using each of them to predict stone clearance. Results: We consecutively enrolled 92 renal units in 89 children with a median age of 9.5 years. Single-session stone clearance was achieved in 76 (82.6%) renal units. Complications occurred with 19 (20.7%) procedures. Stone multiplicity (p = 0.043), staghorn stone (p = 0.007), prior stone treatment (p < 0.001), number of calices involved (p = 0.006), stone burden (p = 0.003), GSS (p < 0.001), S.T.O.N.E. nephrolithometry (p = 0.012), and CROES nomogram (p < 0.001) had significant associations with stone clearance. Only stone attenuation was significantly associated with complications (p = 0.031). For prediction of stone clearance, CROES nomogram demonstrated the greatest area under the ROC curve and the greatest net benefit on decision curve analyses. Conclusions: For children undergoing MPNL, CROES nomogram is the best to predict stone clearance. However, none of the studied scoring systems predicted complications efficiently.


Systemic delayed-type hypersensitivity to cholera toxin and a detoxified derivative.
The delayed-type hypersensitivity (DTH) response to cholera toxin (CT) and an immunopurified formalinized toxoid (TD) was studied in adult BALB/c mice. Intradermal injection of CT in non-immune animals produced substantial footpad oedema which interfered with the measurement of specific DTH but TD proved satisfactory as a challenge antigen. DTH to CT was induced by doses ranging from 0.1 to 10 micrograms, in complete Freund's adjuvant (CFA). The optimal reaction was primed for by 1 microgram CT. Doses of TD with an equivalent B subunit content were equally capable of inducing DTH as the holotoxin. The time-course of the footpad swelling revealed that the DTH response was biphasic. Histological examination showed that the initial swelling was due to tissue oedema and the subsequent increase in footpad thickness was associated with a mononuclear cell infiltrate at the site of antigen challenge. Adoptive transfer experiments were used to demonstrate that the DTH was antigen-specific and could be passively transferred by immune effector T cells. This is the first study to demonstrate an effector T cell response to CT. A role for T cell reactions in the intestinal mucosa must now be examined as a potential contributory mechanism in the prevention of choleraic diarrhoea.


Thermorheological and mechanical properties of copolymers of lactide, isosorbide, and different phthalic acids.
The thermal, rheological, and mechanical behavior of copolymers of lactide, isosorbide, and three different phthalic acids are studied in a wide range of compositions. A linear behavior in glass transition temperature (Tg) with respect to the mole fraction of isosorbide and phthalate content in the copolymers is observed. This behavior is in quantitative agreement with the well-known Di Marzio-Gibbs equation, which correlates the Tg with the mole fraction of flexible bonds in the monomers. The viscoelastic properties are found to obey the Williams-Landel-Ferry (WLF) behavior. This allows us to compare the zero-shear viscosity η0 of all copolymers with different molecular weights at a reference temperature, thus studying the influence of the different phthalic acids on the viscosity. Again, a linear mixing rule on the basis of mole fractions is established in logarithmic scale of viscosities.


Classification of Aortic Stenosis by Flow and Gradient Patterns Provides Insights into the Pathophysiology of Disease.
Different patterns of flow and valve gradients can lead to diagnostic uncertainty about the severity of aortic stenosis (AS). Consecutive patients with severe AS (valve area <1 cm(2)) underwent echocardiography and computed tomography. Patients were classified into 4 groups (high-gradient/normal flow [HGNF], high-gradient/low flow [HGLF], low-gradient/normal flow [LGNF], and low-gradient/low flow [LGLF]). Low flow was defined as stroke volume index <35 mL/m(2) and low gradient as a mean aortic gradient <40 mm Hg. Aortic valve calcification (AVC) was calculated using the Agatston score. Of 181 patients, 56, 30, 46, and 49 had HGNF, HGLF, LGNF and LGLF with median AVC of 2048, 2015, 1366, and 1178 AU/m(2) (P < .0001) and valvuloarterial impedance of 4.5, 6.4, 4.2, and 5.9, respectively (P < .0001). Among those with LGLF, AVC was lower in patients with preserved compared to reduced left ventricular ejection fraction (1018 vs 2550 AU/m(2); P < .0001), but valvuloarterial impedance was similar (P = .33). The LGLF AS with preserved ejection fraction is associated with lower AVC and may identify patients with less severe AS in association with an adaptive ventricular response to high afterload.


Receptor theories and quantitative effect versus dose-concentration relationship.
Both in vivo and in vitro, the dissociation constant K not equal to D50. This was shown for morphine in vivo and for several vasoconstrictors in isolated vascular smooth muscle. When Schild plots are made for a pure competitive antagonist the underlying theory requires that the regression line be constrained to slope -1, for only in this case does pA2 = -log KB, and each has the same confidence limits. Further, even where the slope of the conventional (unconstrained) regression line differs only slightly from -1, the confidence limits of pA2 differ appreciably from those of -log KB. Values of K obtained from pharmacologic methods can discriminate among receptor subtypes. A proper determination of K permits knowledge of the stimulus-response relation, a drug-independent property of the effector system. A perturbation of the drug-receptor equilibrium is a way of determining both k1 and k2; so far, however, we have been successful only with alpha-adrenergic vasoconstrictors in which UV light is a suitable stimulus. Radiolabeled binding appears to be a precise way of determining K's for agonists and antagonists. However, it does not measure an effect; hence we do not know that such binding sites are true receptors unless we can find a correlation between the values obtained for a series of drugs with this method and those obtained with appropriate pharmacologic methods.


Tunable Raman lasing in an As2S3 chalcogenide glass microsphere.
We demonstrate experimentally Raman lasing in an As2S3 chalcogenide glass microsphere pumped by a C-band narrow line laser. Single-mode Raman lasing tunable from 1.610 μm to 1.663 μm is attained when tuning a pump laser wavelength in the 1.522-1.574 μm range. When the pump power significantly exceeds the threshold, multimode cascade Raman lasing is achieved with the maximum Raman order of four at a wavelength of 2.01 μm. We also report an up-converted wave generation at 1.38 μm which is interpreted as the result of four-wave mixing between the pump wave and the wave generated in the second Raman order. The numerical results based on the simulation of the Lugiato-Lefever equation agree with the experimental results.


Outcomes Following Treatment for Carotid Blowout in Head and Neck Cancer Patients.
The aim of the study was to determine outcomes after interventional radiology treatment of carotid blowout. Patients with head and neck cancer and who received interventional radiology treatment for carotid blowout between 2000 and 2022 were included. Pre-treatment, treatment, and post-treatment variables were evaluated. Fourteen patients met inclusion criteria. Eleven patients (78.6%) had a history of radiation. Twelve (85.7%) blowouts occurred within 6 months of recent intervention. Initial treatment was with stenting (n = 9, 64.3%), coil embolization (n = 4, 28.6%), or both (n = 1, 7.1%). Six patients (42.9%) underwent subsequent carotid bypass. Morbidity following treatment included stroke (n = 1) and rebleeding (n = 4). Six-month survival was 57.1%. Of the patients who survived past six months, 5/8 were treated with carotid bypass and coverage. Four patients died of cancer progression, three of rebleeding, and three of medical complications. The majority of carotid blowout occurs within 6 months of surgery or radiation. Many who survive will die of cancer progression or medical illness. Carotid bypass with flap coverage may be a worthwhile treatment for carotid blowout and should be considered as an adjunct to endovascular treatment. Level 4 Laryngoscope, 2023.


Depictions of nursing home residents in US newspapers: successful ageing versus frailty.
The media shape both what people consider significant and how people think about key issues. This paper explored the cultural beliefs and stereotypes that underlie media portrayals of nursing homes. The analysis of texts of 157 articles about nursing homes published from 1999 to 2008 on the front pages of four major-market American newspapers (The New York Times, Chicago Tribune, Los Angeles Times and The Washington Post) was conducted using a qualitative approach inspired by comparative narrative and critical discourse analysis. Results suggest two major themes, each with several narrative components: (a) managing disposable lives (bodies outliving bank accounts; making frailty affordable; and the economics of triage); and (b) retaining purchasing power as successful ageing (consumption as a sign of market participation, spending money as an indicator of autonomy; and financial planning as preparation for future decline). Thus, the results indicate that nursing home residency in-and-of-itself is not a marker of unsuccessful ageing. This, instead, depends, in part, on the extent of choice available as a result of the level of financial solvency. This study shines light on the betwixt and between zone that distinguishes the Third and Fourth Ages; that is, independence versus dependence in old age. If individuals in a nursing home retain control over the management of their lives through the maintenance of financial independence, even if physically frail, association of nursing home residence with the Fourth Age may be ameliorated.


Anatomical, radiographical and computed tomographic study of the limbs skeleton of the Euphrates soft shell turtle (Rafetus euphraticus).
Euphrates turtle is the only soft shell turtle of Iran, and unfortunately is in danger of extinction due to multiple reasons. Imaging techniques, in addition to their importance in diagnosis of injuries to animals, have been used as non-invasive methods to provide normal anatomic views. A few studies have been conducted to understand body structure of the Euphrates turtle. Since there is only general information about the anatomy of turtle limbs, the normal skeleton of the Euphrates limbs was studied. For this purpose four adult Euphrates turtles were used. Digital radiographic examination was performed by computed radiographic (CR) in dorsoventral (DV) and lateral (L) positions. Spiral CT-scanning was done and 3D images of the bones were reconstructed for anatomical evaluation. For skeletal preparation, the skeleton was cleaned by a combination of boiling and mealworm methods and limbs' bones were examined anatomically. In the present study, simultaneous anatomic, radiographic and CT studies of bones in individual turtles made us possible to describe bones anatomically and provided comparable and complementary conditions to represent the abilities of the radiography and CT for better understanding of the anatomy. Arrangement and the number of carpal and tarsal bones are used in turtles' classification. Among the studied species, Euphrates turtle carpal and tarsal bones show the most similarities to the Apolone spinifera.


Visual Outcome of Phacoemulsification versus Small Incision Cataract Surgery in Pseudoexfoliation Syndrome - A Pilot Study.
Available data has highlighted the efficacy of both Phacoemulsification (PHACO) and Small Incision Cataract Surgery (SICS) in the presence of Pseudoexfoliation (PEX) syndrome. In developing countries, both are commonly performed procedures for cataract extraction. But, no direct comparison between these two procedures is available in the setting of PEX syndrome. With this lacuna in mind, this pilot study decided to compare the visual outcomes of both these techniques in the setting of PEX syndrome. To compare and analyze the efficacy and safety of PHACO versus SICS in patients of PEX syndrome who underwent cataract surgery. A prospective, conveniently sampled, observational, pilot study was conducted over six months in ophthalmology department of a tertiary eye institute in India. A total of 200 eyes of 100 patients conforming to pre-defined criteria were conveniently sampled and allotted to two groups of 50 patients each. First group underwent PHACO and second underwent SICS. The demographic profile, pre-operative, intra-operative and post-operative details and complications as well as visual acuity were recorded. Data obtained was analyzed using chi-square test. Statistical significance was set at 95% Confidence Intervals (CI), i.e., at a p-value of <0.05. Of 76 males and 24 females, the mean age was 67.95 years. No statistically significant differences were observed between PHACO and SICS groups with regards to intra-operative complications {overall n=13 in PHACO versus n=21 in SICS, p=0.13}. Controlled sphincterotomy was required in a significantly higher number of SICS cases (p=0.03). No statistically significant differences were observed in terms of post-operative complications (overall n=5 in PHACO versus n=10 in SICS, p=0.26). With careful pre-operative assessment, due to intra-operative modifications and surgical expertise, both PHACO and SICS are apparently safe procedures in PEX syndrome.


A novel combination of the Arndt endobronchial blocker and the laryngeal mask airway ProSeal™ provides one-lung ventilation for thoracic surgery.
In this study, the feasibility and performance of the combination of the Arndt endobronchial blocker and the laryngeal mask airway (LMA) ProSeal™ in airway establishment, ventilation, oxygenation and lung isolation was evaluated. Fifty-five patients undergoing general anesthesia for elective thoracic surgeries were randomly allocated to group Arndt (n=26) or group double-lumen tube (DLT; n=29). Data concerning post-operative airway morbidity, ease of insertion, hemodynamics, lung collapse, ventilators, oxygenation and ventilation were collected for analysis. Compared with group DLT, group Arndt showed a significantly attenuated hemodynamic response to intubation (blood pressure, 149±31 vs. 115±16 mmHg; heart rate, 86±15 vs. 68±15 bpm), less severe injuries to the bronchus (injury score, 1.4±0.2 vs. 0.4±0.1) and vocal cords (injury score, 1.3±0.2 vs. 0.6±0.1), and lower incidences of post-operative sore throat and hoarseness. Furthermore, the novel combination of the Arndt and the LMA ProSeal showed similar ease of airway establishment, comparable ventilation and oxygenation performance, and an analogous lung isolation effect to DLT. The novel combined use of the Arndt endobronchial blocker and the LMA ProSeal can serve as a promising alternative for thoracic procedures requiring one-lung ventilation. The less traumatic properties and equally ideal lung isolation are likely to promote its use in rapidly spreading minimally invasive thoracic surgeries.


Pathophysiology, monitoring, and therapy of acute circulatory problems.
Acute circulatory problems, including shock, traditionally have been recognized and treated by subjective symptoms and vital signs (BP and HR) which represent only superficial aspects of the underlying physiology. Shock, however, is objectively diagnosed, evaluated, and treated using invasive physiologic monitoring to measure cardiac function and output, pulmonary function, and tissue perfusion. Multicomponent noninvasive monitoring systems are now being developed to obtain comparable information and provide continuous display of data on-line, in real time. These monitoring systems may be used to evaluate the effectiveness of alternative therapies, and to titrate therapy to achieve optimal physiologic goals that improve outcome.


Job related affective well-being among primary health care physicians.
Job related affective well-being is important for a healthy life and job satisfaction for all individuals, including physicians. The later group, however, is most often compromised. We aimed to investigate a group of Turkish primary health care physicians' job related emotional perceptions and to assess their reactions in terms of stress, anxiety and depression. A descriptive, cross-sectional, self-reported questionnaire study was conducted. A total of 60 primary health care centres and 274 general practitioners who were working at these centres participated in the study. The response rate was 74%. Printed questionnaires were completed by the participants anonymously. We used the Job Related Affective Well-Being Scale (JAWS) and Depression Anxiety Stress Scale (DASS 42). Correlation analysis and hierarchic regression were performed. Correlations between JAWS and DASS total scores were negative and statistically significant (r = -0.52; P< 0.01). Low pleasure/high arousal (LPHA) and low pleasure/low arousal (LPLA) variations that describe negative emotional states show a positive and significant relationship with depression, anxiety and stress values. The highest mean score was obtained for the high pleasure/low arousal (HPLA) status that can be interpreted to mean that our study group was pleased with their job but was not motivated. Physician's job related negative emotional perceptions are associated with reactions in terms of stress, anxiety and depression. For this reason, it is critical to consider primary care physicians' job related affectations and job related stimuli.


Clinical evaluation of Boswellia serrata (Shallaki) resin in the management of Sandhivata (osteoarthritis).
Sandhigata vata is described under Vatavyadhi in all Ayurvedic texts. Charaka was the first to describe separately "Sandhigata anila", but it was not included under 80 types of nanatmaja vatavyadhi. Osteoarthritis is the most common degenerative joint disease that begins asymptomatically in middle age with progressive symptoms in advancing age. Majority of people by the age 40 years may develop osteoarthritis, especially in weight bearing joints. Females are prone with 25% prevalence, whereas males have a prevalence of 16%. In the present study, 56 patients fulfilling the diagnostic criteria of Sandhigata vata, divided into two groups. Patients of first group were administered with 500 mg capsule of Shallaki, 6 g per day (in three divided doses) with lukewarm water (n=29) and the second group) capsule Shallaki as above along with local application of Shallaki ointment on the affected joints (n=23). After a course of therapy for 2 months, symptomatic improvement was observed in both the groups at various levels with promising results in the patients of first group.


Dielectrophoretic isolation and detection of cfc-DNA nanoparticulate biomarkers and virus from blood.
Dielectrophoretic (DEP) microarray devices allow important cellular nanoparticulate biomarkers and virus to be rapidly isolated, concentrated, and detected directly from clinical and biological samples. A variety of submicron nanoparticulate entities including cell free circulating (cfc) DNA, mitochondria, and virus can be isolated into DEP high-field areas on microelectrodes, while blood cells and other micron-size entities become isolated into DEP low-field areas between the microelectrodes. The nanoparticulate entities are held in the DEP high-field areas while cells are washed away along with proteins and other small molecules that are not affected by the DEP electric fields. DEP carried out on 20 μL of whole blood obtained from chronic lymphocytic leukemia patients showed a considerable amount of SYBR Green stained DNA fluorescent material concentrated in the DEP high-field regions. Whole blood obtained from healthy individuals showed little or no fluorescent DNA materials in the DEP high-field regions. Fluorescent T7 bacteriophage virus could be isolated directly from blood samples, and fluorescently stained mitochondria could be isolated from biological buffer samples. Using newer DEP microarray devices, high-molecular-weight DNA could be isolated from serum and detected at levels as low as 8-16 ng/mL.


Activity of high dose 24 hour 5-fluorouracil infusion plus L-leucovorin in advanced colorectal cancer.
Modulation of 5-fluorouracil (5-FU) by leucovorin (L-LV) in patients (pts) with advanced colorectal cancer has been demonstrated to produce a highly significant benefit over single-agent 5-FU in terms of tumor response rate, but this advantage does not translate into an evident improvement of overall survival. To improve the clinical efficacy of the 5-FU plus L-LV regimen a phase II study of weekly 24-hour high-dose 5-FU infusion with L-LV was undertaken. Seventy advanced colorectal patients were enrolled and treated by a weekly outpatient combination regimen according to the following schedule: L-LV 100 mg/sqm by 4 hours i.v. infusion followed by 5-FU 2600 mg/sqm over a 24 hours infusion combined with a fixed dose of oral L-LV (50 mg) every 4 hours for 5 times. Forty-four pts did not receive any previous CT and 26 pts were pretreated with fluoropyrimidines. The overall objective response rate (OR) was 35.3%; 7 CR and 11 PR (42.8% OR) were observed in the group of untreated pts, and 6 PR (23% OR) were reported among previously treated pts. Major side effects were represented by diarrhoea (grade III: 26%, grade IV: 1%), hand-foot syndrome (grade III: 4%, grade IV: 1%) and mucositis (grade III: 4%); however, this did not significantly influence the therapeutic programme. Median 5-FU dose intensity was 100% and 80% at 4 weeks, 87% and 75% at 8 weeks in untreated and pretreated pts, respectively. L-Leucovorin modulation of weekly short-term continuous infusion of high-dose 5-fluorouracil appeared a well-tolerated outpatient regimen; it demonstrated a high activity in advanced colorectal cancer, both in untreated pts and in pts resistant to 5-FU-based chemotherapy.


Design, synthesis, and evaluation of new thiadiazole-based direct inhibitors of enoyl acyl carrier protein reductase (InhA) for the treatment of tuberculosis.
Mycobacterial enoyl acyl carrier protein reductase (InhA) is a clinically validated target for the treatment of tuberculosis infections, a disease that still causes the death of at least a million people annually. A known class of potent, direct, and competitive InhA inhibitors based on a tetracyclic thiadiazole structure has been shown to have in vivo activity in murine models of tuberculosis infection. On the basis of this template, we have here explored the medicinal chemistry of truncated analogues that have only three aromatic rings. In particular, compounds 8b, 8d, 8f, 8l, and 8n show interesting features, including low nanomolar InhA IC50, submicromolar antimycobacterial potency, and improved physicochemical profiles in comparison with the tetracyclic analogues. From this series, 8d is identified as having the best balance of potency and properties, whereby the resolved 8d S-enatiomer shows encouraging in vivo efficacy.


Langer's axillary arch: a rare variant, and prevalence among Caucasians.
During the dissection of a 79-year-old Caucasian female cadaver, a variant of Langer's axillary arch was found unilaterally in the left axilla. While Langer's axillary arches are not uncommon, this particular variant, attaching to the biceps brachii, is much rarer with a reported prevalence of only 0.25%. The case reported here, however, is only the third example of a Langer's axillary arch that has been found in the last 14 years in the Dissecting Room at St. George's, University of London, giving it an overall prevalence of approximately 1.0% amongst a population of around 280 Caucasian cadavers, much lower than the reported frequency of 7%. Langer's axillary arches can be completely asymptomatic in life, but may also cause a variety of issues both clinically and surgically.