Histone acetylation and recruitment of serum responsive factor and CREB-binding protein onto SM22 promoter during SM22 gene expression.
Chromatin acetylation and deacetylation catalyzed by histone acetyltransferases (HATs) and histone deacetylases (HDACs) are closely related to eukaryotic gene transcription. Although the binding of serum response factor (SRF) to the CArG boxes in the promoter region is necessary for SM22 expression, it has never been examined whether the local chromatin modification is involved in SM22 gene regulation. In this study, we used the SM22 gene as a model to address whether transcriptional activation of the gene can be manipulated through adjusting histone acetylation of the chromatin template and whether SRF- and HAT-containing coactivators can be recruited onto the SM22 promoter region during gene activation. Here, we showed that the stimulation of the SM22 promoter by the coactivator CREB-binding protein (CBP) was dependent on HAT activity. Overexpression of HDACs decreased SM22 promoter activity, whereas trichostatin A, an HDAC inhibitor, stimulated SM22 promoter activity in a CArG box-dependent manner and induced endogenous SM22 gene expression. Chromatin immunoprecipitation assays showed that trichostatin A treatment in 10T1/2 cells induces chromatin hyperacetylation in the SM22 gene. Although histone hyperacetylation of the SM22 gene occurred during SM22 gene expression and SRF and CBP immunocomplexes possess HAT activities in smooth muscle cells, both SRF and CBP were recruited to the CArG box-containing region of the promoter. This study provides evidence that chromatin acetylation is involved in smooth muscle cell-specific gene regulation.


[Study on determinationing the bone mineral content as diagnostic value for occupational fluorosis].
The results of determination of the bone density of 194 workers exposed to fluorine by SPA-III type osteodensimeter were compared with people unexposed to fluorine, and with the results of diagnosing the luorosis by X-ray. (1) The abnormal bone cortex thickness and density rate in the people exposed to fluorine was significantly higher than the ordinary people (P < 0.05). (2) In the people exposed to fluorine, the correspondency rate of determining fluorosis of bone by X-ray and by osteodensimeter were 84.6%, and results of the two methods had no significant difference (P > 0.05). (3) In another group of 155 cases, whose values of hair fluorine and urinary fluorine were higher than the ordinary people (66.5%), the abnormal density of bone of 103 cases had been determined by osteodensimeter, but not by X-ray. This showed that the diagnosis of early changes of osteofluorosis by osteodensimeter was more sensitive than by X-ray. (4) There was close association between the unusual rate of osteodensity and the superstandard rate of hair fluorine and urinary fluorine. The above findings indicated the determination of bone density can be used as a diagnostic index for occupational fluorosis.


Indications for Swan-Ganz catheterization.
The Swan-Ganz catheter provides a relatively easy means of obtaining a wealth of information about intracardiac pressures and flows. The catheter also is useful for intracardiac pacing. Because any invasive procedure entails some risk, albeit small in the case of the Swan-Ganz catheter, insertion of a catheter usually is reserved for hemodynamically unstable patients and/or those in whom information relevant to clinical management can be obtained only by this means. In such circumstances the catheter has been extraordinarily useful, and further refinements undoubtedly will make it even more useful in the future.


Location, Location, Location: Characteristics and Services of Long-Stay Home Care Recipients in Retirement Homes Compared to Others in Private Homes and Long-Term Care Homes.
We examine recipients of publicly funded ongoing care in a single Ontario jurisdiction who reside in three different settings: long-stay home care patients in private homes and apartments, other patients in retirement homes and residents of long-term care homes, using interRAI assessment instruments. Among home care patients, those in retirement homes have higher proportions of dementia and moderate cognitive impairment, less supportive informal care systems as well as more personal care and nursing services above those provided by the public home care system, more frequent but shorter home support visits and lower than expected public home care expenditures. These lower expenditures may be because of efficiency of care delivery or by retirement homes providing some services otherwise provided by the public home care system. Although persons in each setting are mostly older adults with high degrees of frailty and medical complexity, long-term care home residents show distinctly higher needs. We estimate that 40% of retirement home residents are long-stay home care patients, and they comprise about one in six of this Community Care Access Centre's long-stay patients.


Perioperative Management of Pheochromocytomas and Sympathetic Paragangliomas.
Pheochromocytomas and paragangliomas (PPGLs) are rare neuroendocrine tumors arising from chromaffin cells of the adrenal medulla or extra-adrenal paraganglia, respectively. PPGLs have the highest degree of heritability among endocrine tumors. Currently, ~40% of individuals with PPGLs have a genetic germline and there are at least 12 different genetic syndromes related to these tumors. Metastatic PPGLs are defined by the presence of distant metastases at sites where chromaffin cells are physiologically absent. Approximately 10% of pheochromocytomas and ~40% of sympathetic paragangliomas are linked to metastases, explaining why complete surgical resection is the first-choice treatment for all PPGL patients. The surgical approach is a high-risk procedure requiring perioperative management by a specialized multidisciplinary team in centers with broad expertise. In this review, we summarize and discuss the most relevant aspects of perioperative management in patients with pheochromocytomas and sympathetic paragangliomas.


[Activated factor of immature neurons for excessive apoptosis induced by exogenous glucocorticosteroid].
To confirm the key inducing factor of excessive apoptosis in immature brain under the exposure of exogenous glucocorticosteroid and observe the characteristics of mitochondrial oxidative stress and intracellular [Ca(2+)]i overload as compared to healthy adult rats. A total of 192 healthy Sprague-Dawley (SD) rats selected for the study were divided into three groups including PD7, PD15 and PD60 corresponding human age stages including full-term newborn, one-year infant and adult respectively. To mimic the therapeutic regime for infantile spasms, 8 rats in each group was treated with prednisone (6 mg x kg(-1) x d(-1)), ACTH (150 U x m(-2) x d(-1)), normal saline for 4 days and drug withdrawal for 3 weeks. Rats were deeply anesthetized and sacrificed by decapitation. The mitochondrial concentrations of GSH, SOD, MDA, Na(+)-K(+)-ATPase and intracellular [Ca2+i] were all determined by spectrophotometer. The cellular NMDA-R1 expression was measured by immunohistochemistry. Both prednisone and ACTH caused neuron reduced and TUNEL-positive cell increased in the frontal lobe, specially in PD7 group of prednisone, that were 77.7 +/- 4.7 neurons per VF (control group: 102.3 +/- 5.9) (P = 0.002), 114.8 +/- 8.14 (control group: 56.3 +/- 5.6) (P = 0.029) respectively. The mitochondrial levels of GSH, SOD and Na+-K+-ATPase decreased after prednisone and ACTH administration at different level in different age groups whereas the concentration of MDA increased. These changes were significant in PD7 group after prednisone administration, that were 158.3 +/- 6.1 mg/g prot of GSH (control group: 225.1 +/- 9.5 mg/g prot) (P = 0.006), 155.8 +/- 4.3 U/mg prot of SOD (control group: 228.1 +/- 9.2 U/mg prot) (P = 0.006), 14.6 +/- 3.5 U/mg prot of Na+-K+-ATPase (control group: 20.8 +/- 5.5 U/mg prot) and 10.4 +/- 0.9 nmol/mg prot of MDA (control group: 4.8 +/- 1.9 nmol/mg prot) (all P < 0.01). [Ca(2+)]i level in neuron increased, specially in PD7 group after prednisone administration, that was 164.6 +/- 11.9 nmol/L (control group: 125.8 +/- 6.03 nmol/L) (P = 0.003). Similar to [Ca(2+)]i changes, the density of NMDA-R1 also increased mostly in PD7 group after prednisone administration, that was 0.36 +/- 0.03 (control group: 0.21 +/- 0.05) while that was only 0.18 +/- 0.05 in PD60 group (control group: 0.15 +/- 0.02). At 3 weeks post-dosing, all of them returned to normal level. Dysfunctions of oxidation and antioxidation in mitochondria of immature neurocytes are induced by prednisone or ACTH within the therapeutic levels. Enhanced expressions of NMDA-R1, Bax and superoxide contribute to excessive apoptosis of immature neurocytes induced by exogenous glucocorticosteroid. The possible determining factors for immature brain is more vulnerable to exogenous glucocorticosteroid damage. It may be associated with the physiologically high intracellular level of calcium concentration and NMDA-R1 expression.


Effects of Cooling During Exercise on Thermoregulatory Responses of Men With Paraplegia.
People with spinal cord injury (SCI) have an altered afferent input to the thermoregulatory center, resulting in a reduced efferent response (vasomotor control and sweating capacity) below the level of the lesion. Consequently, core body temperature rises more rapidly during exercise in individuals with SCI compared with people who are able-bodied. Cooling strategies may reduce the thermophysiological strain in SCI. The aim of this study was to examine the effects of a cooling vest on the core body temperature response of people with a thoracic SCI during submaximal exercise. Ten men (mean age=44 years, SD=11) with a thoracic lesion (T4-T5 or below) participated in this randomized crossover study. Participants performed two 45-minute exercise bouts at 50% maximal workload (ambient temperature 25°C), with participants randomized to a group wearing a cooling vest or a group wearing no vest (separate days). Core body temperature and skin temperature were continuously measured, and thermal sensation was assessed every 3 minutes. Exercise resulted in an increased core body temperature, skin temperature, and thermal sensation, whereas cooling did not affect core body temperature. The cooling vest effectively decreased skin temperature, increased the core-to-trunk skin temperature gradient, and tended to lower thermal sensation compared with the control condition. The lack of differences in core body temperature among conditions may be a result of the relative moderate ambient temperature in which the exercise was performed. Despite effectively lowering skin temperature and increasing the core-to-trunk skin temperature gradient, there was no impact of the cooling vest on the exercise-induced increase in core body temperature in men with low thoracic SCI.


Phloretin attenuates behavior deficits and neuroinflammatory response in MPTP induced Parkinson's disease in mice.
Neuroinflammation is one of the significant neuropathological conditions in Parkinson's disease (PD) which is due to microglial and astrocytes activation leads to progressive dopaminergic neuronal loss. To date, Current PD drugs offers only symptomatic relief with adverse effects and lack of ability to prevent the progression of neurodegeneration. Therefore, a better approach to develop a multi potent drug of natural origin would be beneficial in managing the disease. Therefore, the present study aimed to investigate the neuroprotective and anti-inflammatory effects of PHL by exploring its neuroprotective mechanism in 1-methyl-4-phenyl-1,2,3,6-tetrahydro pyridine (MPTP) induced PD in mice. MPTP intoxication in mice cause motor abnormalities, decreased dopamine (DA) levels, reduced tyrosine hydroxylase (TH) enzyme protein expression and inflammation which were effectively restored by PHL. Moreover gliotic specific inflammatory markers like glial fibrillary acidic protein (GFAP), ionized calcium-binding adaptor protein-1 (Iba-1), iNOS and COX-2 were found to be expressed more in MPTP intoxicated mice, Further the levels of proinflammatory cytokines like IL-β, IL-6, and TNF-α were significantly upregulated in MPTP intoxicated mice, these deleterious responses were diminished to extend neuroprotection by PHL treatment. Our findings strongly suggest PHL as a potent therapeutic agent in treating PD.


Functional proteomic analyses of Bothrops atrox venom reveals phenotypes associated with habitat variation in the Amazon.
Venom variability is commonly reported for venomous snakes including Bothrops atrox. Here, we compared the composition of venoms from B. atrox snakes collected at Amazonian conserved habitats (terra-firme upland forest and várzea) and human modified areas (pasture and degraded areas). Venom samples were submitted to shotgun proteomic analysis as a whole or compared after fractionation by reversed-phase chromatography. Whole venom proteomes revealed a similar composition among the venoms with predominance of SVMPs, CTLs, and SVSPs and intermediate amounts of PLA2s and LAAOs. However, when distribution of particular isoforms was analyzed by either method, the venom from várzea snakes showed a decrease in hemorrhagic SVMPs and an increase in SVSPs, and procoagulant SVMPs and PLA2s. These differences were validated by experimental approaches including both enzymatic and in vivo assays, and indicated restrictions in respect to antivenom efficacy to variable components. Thus, proteomic analysis at the isoform level combined to in silico prediction of functional properties may indicate venom biological activity. These results also suggest that the prevalence of functionally distinct isoforms contributes to the variability of the venoms and could reflect the adaptation of B. atrox to distinct prey communities in different Amazon habitats. In this report, we compared isoforms present in venoms from snakes collected at different Amazonian habitats. By means of a species venom gland transcriptome and the in silico functional prediction of each isoform, we were able to predict the principal venom activities in vitro and in animal models. We also showed remarkable differences in the venom pools from snakes collected at the floodplain (várzea habitat) compared to other habitats. Not only was this venom less hemorrhagic and more procoagulant, when compared to the venom pools from the other three habitats studied, but also this enhanced procoagulant activity was not efficiently neutralized by Bothrops antivenom. Thus, using a functional proteomic approach, we highlighted intraspecific differences in B. atrox venom that could impact both in the ecology of snakes but also in the treatment of snake bite patients in the region.


Depression in the wives of convicted men: prevalence and associated factors.
To estimate the prevalence of depression and to identify the main risk factors associated with depression in wives of convicted men. Descriptive, cross - sectional, quantitative approach. The data were collected with 349 female partners of convicted patients in three penitentiaries in the state of Paraná, with a semistructured research, between January and June of 2016, being compiled in a database and analyzed using SPSS® 20.0 software. It was possible to identify vulnerability to depression among wives of convicted men, most were young and 42.2% have or already had depression. It was verified that the variables to depression were ages equal to or above 30 years (50.3%, p <0.001), smoking (61.1%, p <0.013) and alcoholism (16.1%, p <0.001). It is the responsibility of the nurse with the multidisciplinary health team to invest in health promotion and prevention actions against these risk factors that were associated with depression in this population.


The loss of DLG2 isoform 7/8, but not isoform 2, is critical in advanced staged neuroblastoma.
Neuroblastoma is a childhood neural crest tumor showing large clinical and genetic heterogeneity, one form displaying 11q-deletion is very aggressive. It has been shown that 11q-deletion results in decreased expression of DLG2, a gene residing in the deleted region. DLG2 has a number of different isoforms with the main difference is the presence or absence of a L27 domain. The L27 domain containing DLG proteins can form complexes with CASK/MPP and LIN7 protein family members, which will control cell polarity and signaling. We evaluated the DLG gene family and the LIN7 gene family for their expression in differently INSS staged neuroblastoma from publically available data and primary tumors, we included two distinct DLG1 and DLG2 N-terminal transcript isoforms encoding L27 domains for their expression. Functionality of DLG2 isoforms and of LIN7A were evaluated in the 11q-deleted neuroblastoma cell line SKNAS. In neuroblastoma only two DLG2 isoforms were expressed: isoform 2 and isoform 7/8. Using the array data we could determine that higher expression of DLG members that contain L27 domains correlated to better survival and prognosis. Whilst DLG1 showed a decrease in both isoforms with increased INSS stage, only the full length L27 containing DLG2 transcripts DLG2-isoform 7/8 showed a decrease in expression in high stage neuroblastoma. We could show that the protein encoded by DLG2-isoform 7 could bind to LIN7A, and increased DLG2-isoform 7 gene expression increased the expression of LIN7A, this reduced neuroblastoma cell proliferation and viability, with increased BAX/BCL2 ratio indicating increased apoptosis. We have provided evidence that gene expression of the L27 domain containing DLG2-isoform 7/8 but not L27 domain lacking DLG2-isoform 2 is disrupted in neuroblastoma, in particular in the aggressive subsets of tumors. The presence of the complete L27 domain allows for the binding to LIN7A, which will control cell polarity and signaling, thus affecting cancer cell viability.


Studies on the constituents of Broussonetia species. II. Six new pyrrolidine alkaloids, broussonetine A, B, E, F and broussonetinine A and B, as inhibitors of glycosidases from Broussonetia kazinoki Sieb.
Six new pyrrolidine alkaloids called broussonetine A, B, E, F, and broussonetinine A and B were isolated from the branches of Broussonetia kazinoki Sieb. (Moraceae). Broussonetine A, B, E and F were formulated as 2 beta-hydroxymethyl-3 beta-hydroxy-5-alpha- (10-oxo-13-hydroxytridecyl)-pyrrolidine-4-O-beta-D-glucopyranoside (1), 2 beta-hydroxymethyl-3 beta-hydroxy-5 alpha-(9-oxo-13-hydroxytridecyl)-pyrrolidine-4-O-beta-D-glucopy ran oside (2), 2 beta-hydroxymethyl-3 alpha,4 beta-dihydroxy-5 alpha-(1,13-dihydroxy-10-oxo-tridecyl)-pyrrolidine (3), and 2 beta-hydroxymethyl-3 alpha,4 beta-dihydroxy-5 alpha-(1,13-dihydroxy-9-oxo-tridecyl)-pyrrolidine (4), respectively. Broussonetinine A and B (5 and 6) were also isolated and identified as the aglycones of 1 and 2. 3 and 4 exhibited a strong inhibition of alpha-glucosidase, beta-glucosidase, beta-galactosidase and beta-mannosidase, while 5 and 6 showed a strong inhibition of beta-galactosidase and alpha-mannosidase.


Kinetics and thermodynamics of association of a phospholipid derivative with lipid bilayers in liquid-disordered and liquid-ordered phases.
We have measured the rates of insertion into, desorption from, and spontaneous interlayer translocation (flip-flop) in liquid-disordered and liquid-ordered phase lipid bilayer membranes, of the fluorescent phospholipid derivative NBD-dimyristoylphosphatidyl ethanolamine. This study made use of a recently described method that exploits a detailed knowledge of the binding kinetics of an amphiphile to bovine serum albumin, to recover the insertion and desorption rate constants when the albumin-bound amphiphile is transferred through the aqueous phase to the membrane and vice versa. The lipid bilayers, studied as large unilamellar vesicles, were prepared from pure 1-palmitoyl-2-oleoylphosphatidylcholine in the liquid-disordered phase; and from two cholesterol-containing binary lipid mixtures, 1-palmitoyl-2-oleoylphosphatidylcholine and cholesterol (molar ratio of 1:1), and egg sphingomyelin and cholesterol (molar ratio of 6:4), both in the liquid-ordered phase. Insertion, desorption, and translocation rate constants and equilibrium constants for association of the amphiphile monomer with the lipid bilayers were directly measured between 15 degrees and 35 degrees C, and the standard free energies, enthalpies, and entropies, as well as the activation energies for these processes, were derived from this data. The equilibrium partition coefficients for partitioning of the amphiphile between the aqueous phase and the different membrane phases were also derived, and permitted the estimation of hypothetical partition coefficients and the respective energetic parameters for partitioning between the different lipid phases if these were to coexist in the same membrane.


Modulation of vascular endothelial cell function by palm oil antioxidants.
Several cardiovascular risk factors including, hypercholesterolaemia and hypertension, lead to diseased blood vessels due to endothelial cell dysfunction. Recent studies also indicate that such alterations in blood vessel function may involve free radical related mechanism(s). Therefore, in the present study, two different preparations of palm oils with variable antioxidant profiles, as well as a purified antioxidant fraction extracted from unprocessed palm oil (tocotrienol-rich-factor; TRF), were tested for their ability to influence blood vessel dysfunction in the spontaneously hypertensive rat (SHR). Adult SHRs were fed a synthetic diet supplemented (5% w/w) with either physically refined palm oil (PO), golden palm cooking oil (Nutrolein; GPO) or olive oil (OO; control diet). Antioxidant rich diet (TRF diet) was prepared by supplementing the OO diet with 0.2% (w/w) TRF. After 12 weeks of pre-feeding, segments of thoracic aorta were used to evaluate vascular function. Compared to the normotensive Wistar-Kyoto (WKY) control rats, aortic rings from the SHR showed impaired endothelium dependent relaxation to acetylcholine (ACh) which was restored by dietary TRF (p<0.05, ANOVA and Tukey's test). In addition, the paradoxical increase in tension in control hypertensive vessels observed at higher doses of ACh was prevented by TRF and also by the PO and GPO diets. Although the development of thromboxane-like constrictor response, after the inhibition of nitric oxide in hypertensive vessels, was unaffected by test diets, both TRF and GPO feeding prevented the amplification of this unwanted constriction by a threshold dose (7.2x10-10 M) of noradrenaline. Results suggest a modulatory role for minor constituents of edible oils and are in agreement with the recently reported benefits of natural antioxidants against cardiovascular diseases.


Chiral diphosphites derived from D-glucose: new highly modular ligands for the asymmetric catalytic hydrogenation.
A series of novel diphosphite ligands derived from readily available D-(+)-glucose have been synthesized. These ligands were screened in the Rh-catalyzed hydrogenation of a series of alpha,beta-unsaturated carboxylic acid derivatives. Both excellent enantioselectivities (ee up to >99%) and activities were achieved. The advantage of these ligands is that their modular nature allows an easy systematic variation in the configuration of the stereocenters (C-3, C-5) at the ligand backbone and in the biaryl substituents, so the optimum configuration for maximum enantioselectivity in asymmetric hydrogenation can be determined. Results show that enantiomeric excesses depend strongly on the absolute configuration of C-3 and slightly on the stereocenter carbon C-5, while the sense of the enantiodiscrimination is predominantly controlled by the configuration of the biaryls at the phosphite moieties. Moreover, the presence of bulky substituents at the ortho-positions of the biaryl diphosphite moieties has a positive effect on enantioselectivity.


Imaging at ultrahigh magnetic fields: History, challenges, and solutions.
Following early efforts in applying nuclear magnetic resonance (NMR) spectroscopy to study biological processes in intact systems, and particularly since the introduction of 4 T human scanners circa 1990, rapid progress was made in imaging and spectroscopy studies of humans at 4 T and animal models at 9.4 T, leading to the introduction of 7 T and higher magnetic fields for human investigation at about the turn of the century. Work conducted on these platforms has provided numerous technological solutions to challenges posed at these ultrahigh fields, and demonstrated the existence of significant advantages in signal-to-noise ratio and biological information content. Primary difference from lower fields is the deviation from the near field regime at the radiofrequencies (RF) corresponding to hydrogen resonance conditions. At such ultrahigh fields, the RF is characterized by attenuated traveling waves in the human body, which leads to image non-uniformities for a given sample-coil configuration because of destructive and constructive interferences. These non-uniformities were initially considered detrimental to progress of imaging at high field strengths. However, they are advantageous for parallel imaging in signal reception and transmission, two critical technologies that account, to a large extend, for the success of ultrahigh fields. With these technologies and improvements in instrumentation and imaging methods, today ultrahigh fields have provided unprecedented gains in imaging of brain function and anatomy, and started to make inroads into investigation of the human torso and extremities. As extensive as they are, these gains still constitute a prelude to what is to come given the increasingly larger effort committed to ultrahigh field research and development of ever better instrumentation and techniques.


Of two minds: forming and changing valence-inconsistent implicit and explicit attitudes.
Because different processes underlie implicit and explicit attitudes, we hypothesized that they are differentially sensitive to different kinds of information. We measured implicit and explicit attitudes over time, as different types of attitude-relevant information about a single attitude object were presented. As expected, explicit attitudes formed and changed in response to the valence of consciously accessible, verbally presented behavioral information about the target. In contrast, implicit attitudes formed and changed in response to the valence of subliminally presented primes, reflecting the progressive accretion of attitude object-evaluation pairings. As a consequence, when subliminal primes and behavioral information were of opposite valence, people formed implicit and explicit attitudes of conflicting valence.


Food insecurity and adult overweight/obesity: Gender and race/ethnic disparities.
The majority of the food insecurity-obesity research has indicated a positive association among women, especially minority women. Less research has been conducted on men, and the findings are inconsistent. The aim was to assess whether gender and race/ethnic disparities exists between the food insecurity and overweight/obesity relationship among adults ages 18-59. We used the cross-sectional 2011 and 2012 National Health Interview Survey data (N = 19,990). Three or more affirmative responses on the 10-item USDA Food Security Scale indicated food insecure experiences. Self-reported height and weight were used to calculate body mass index according to the Centers for Disease Control and Prevention. Multivariate logistic regression models were stratified by gender and race/ethnicity to estimate the association between food insecurity and overweight/obesity controlling for several demographic characteristics. Adults on average were 36 years of age (51% female; 56% white, 27% Hispanic, and 17% black), 27% were food insecure, and 65% were overweight/obese. Food insecurity was most prevalent among blacks and Hispanics, regardless of gender. A greater percentage of food insecure women were overweight/obese compared to food secure women among all race/ethnicity groups; while similar proportions of white, black, and Hispanic men were overweight/obese irrespective of their food security status. In covariate-adjusted models, food insecurity was associated with a 41% and 29% higher odds of being overweight/obese among white and Hispanic women, respectively. Food insecurity was not related to overweight/obesity among black women nor among white, black, and Hispanic men. The complex relationship between food insecurity and obesity suggests a need to investigate potential behavioral and physiological mechanisms, and moderators of this relationship.


Survey of antimicrobial stewardship practices in public hospitals in New Zealand district health boards.
To determine what antimicrobial stewardship (AMS) practices exist in New Zealand public hospitals. A quantitative survey based on recommended components of hospital AMS programmes was sent to the 20 DHBs in June 2016. Ten of the 20 DHBs had an AMS committee, nine had dedicated AMS pharmacist full-time equivalents (FTEs) and eight had lead clinician FTEs. Only one DHB met FTE recommendations for AMS pharmacists and two for clinicians (0.3 and 0.1 FTEs per 100 acute beds, respectively). All DHBs had conducted at least one antimicrobial audit in the preceding 12 months, most had their own antimicrobial guidelines (19/20) and prescribing policies (18/20), and 12 reported on antimicrobial usage by at least one metric (eg, defined daily doses). Staff education on AMS had been given at most DHBs in the previous year, but only three reported having AMS ward rounds. All DHBs had surveillance programmes for resistant organisms and most produced antibiograms (16/20). All reported barriers to implementation of an AMS programme. Hospital AMS programmes are in their infancy in New Zealand, with wide variation in practices seen. National co-ordination is required to assist DHBs in developing effective programmes to improve antimicrobial use.


Biatriosporin D displays anti-virulence activity through decreasing the intracellular cAMP levels.
Candidiasis has long been a serious human health problem, and novel antifungal approaches are greatly needed. During both superficial and systemic infection, C. albicans relies on a battery of virulence factors, such as adherence, filamentation, and biofilm formation. In this study, we found that a small phenolic compound, Biatriosporin D (BD), isolated from an endolichenic fungus, Biatriospora sp., displayed anti-virulence activity by inhibiting adhesion, hyphal morphogenesis and biofilm formation of C. albicans. Of note is the high efficacy of BD in preventing filamentation with a much lower dose than its MIC value. Furthermore, BD prolonged the survival of worms infected by C. albicans in vivo. Quantitative real-time PCR analysis, exogenous cAMP rescue experiments and intracellular cAMP measurements revealed that BD regulates the Ras1-cAMP-Efg1 pathway by reducing cAMP levels to inhibit the hyphal formation. Further investigation showed that BD could upregulate Dpp3 to synthesize much more farnesol, which could inhibit the activity of Cdc35 and reduce the generation of cAMP. Taken together, these findings indicate that BD stimulates the expression of Dpp3 to synthesize more farnesol that directly inhibits the Cdc35 activity, reducing intracellular cAMP and thereby disrupting the morphologic transition and attenuating the virulence of C. albicans. Our study uncovers the underlying mechanism of BD as a prodrug in fighting against pathogenic C. albicans and provides a potential application of BD in fighting clinically relevant fungal infections by targeting fungal virulence.


Transfer factor therapy in mycosis fungoides: a double-blind study.
Sixteen patients with mycosis fungoides (MF) were given either active transfer factor (TF) or heat-inactivated TF as additional therapy to topical nitrogen mustard or PUVA. The TF was prepared from non-selected healthy blood donors. The clinical evaluation after 2 years of therapy showed that among 8 patients treated with active TF, none went into complete remission of their disease 4 patients had partial remission, one was unchanged, 2 progressed, and one died of active MF. In the placebo-treated group, 5 patients achieved complete remission and 2 partial remission. One patient died early in the trial due to cardiac disease. Immunological studies during the first year of therapy revealed cutaneous anergy towards tuberculin in most patients. This anergy did not change during TF therapy and differed from normal lymphocyte reactivity in vitro after tuberculin stimulation. At the start of treatment the patients had diminished levels of T lymphocytes in peripheral blood. A temporary increase was observed in the total number of T lymphocytes in patients after one month of treatment with active TF. After one year the T lymphopenia had disappeared in both groups. The mitogen reactivity of lymphocytes was found to be normal (PHA, PWM) or somewhat reduced (Con A). It is concluded that under the conditions employed in this trial, TF was not able to prevent progression of early mycosis fungoides, when viewed over a period of 2 years.


The SV40 termination region exhibits an altered helical DNA conformation.
The DNA structure of a fragment containing the SV40 termination sequences was examined using gel mobility assays. The region is shown to contain a DNA bend as evidenced by an abnormal mobility that is progressively accentuated as the temperature is lowered. This represents the strongest example of DNA bending among the collection of SV40 fragments studied. The same fragment was shown previously to uniquely support hyper-stable nucleosome formation in vitro, suggesting a possible relationship between DNA bending and nucleosome stability.


A Case of Masson's Tumor of the Penis Presenting as Chronic Pelvic Pain Syndrome.
The intravascular papillary endothelial hyperplasia (IPEH) or Masson's tumor is an unusual and rare benign disease.It is histologically characterized by papillary and anastomosing channel-like structures lined by proliferating e n dothelium. Radiologically, it is usually presented as a heterogenic solid mass with contrast enhancement, withareas resembling necrosis and thrombosis. These signs can easily be attributed to malignancy. The urogenital tractis extremely rarely affected with only 8 cases described in the kidneys and one of the penis. We present a rarecase of IPEH at the base of the penis, visible only on MRI, causing chronic pelvic pain and erectile dysfunction.According to available English literature our case is the first in this pelvic location and only the second to affect thepenis. Radical excision of the formation cured the condition.


Water sorption and solubility of resin-modified polyalkenoate cements.
The purpose of this study was to compare the water sorption and solubility of several resin-modified polyalkenoate cements. The materials evaluated included Variglass used as a restoration, base on liner; Fuji II LC, Fuji Liner; Vitrebond; Vitremer and Photac-Bond. Z100, a composite resin, was used as control. All specimens were manipulated according to the manufacturers' instructions and then subjected to water sorption and solubility tests based on the ISO 4049 requirements. Data were subjected to one-way ANOVA and Duncan's test at a 0.05 significance level. Results show that the composite resin control had significantly less water sorption than any of the resin-modified polyalkenoate cements evaluated. The degree of water sorption was product dependent and appeared to be influenced by the resin (HEMA) content. There was no apparent correlation between water sorption and solubility. Some of the resin-modified polyalkenoate cements retained water in their set structure and hence solubility could not be assessed.


Does the Start of Dialysis Initiate a Period of Increased Risk of Ulceration or Amputation?
Dialysis therapy is associated with an increased incidence of lower-extremity wounds and amputations. We compared the incidence of foot ulcers and amputations before and after the start of dialysis. We evaluated 150 consecutive diabetic patients receiving dialysis and compared the incidence of foot complications 30 months before and after initiation of hemodialysis. We used claims data for diabetes, ulceration, and dialysis and abstracted medical records to verify diagnoses and dates of ulcers and amputations. We compared initial and cumulative ulcer/amputation incidence to account for multiple events in the same person over time. We used the same formula to determine the incidence rate difference and 95% confidence intervals (CIs) to compare new ulcers and amputations during the study. There was no significant difference in the incidence of first foot ulcers before (91.7 per 1,000 patient-years; 95% CI, 73.7-112.3 per 1,000 patient-years) and after (82.7; 95% CI, 65.7-102.3) the start of hemodialysis. The incidence of cumulative ulcers was significantly higher before (304.0 per 1,000 patient-years; 95% CI, 270.8-340.2) compared with after (210.7 per 1,000 patient-years; 95% CI, 183.0-240.9) dialysis. There was no difference in the incidence of first amputation before (29.3 per 1,000 patient-years; 95% CI, 1 9.4-41.7 per 1,000 patient-years) and after (37.3 per 1,000 patient-years; 95% CI, 19.4-41.7 per 1,000 patient-years) dialysis or in the cumulative incidence of amputations before (61.3 per 1,000 patient-years; 95% CI, 46.7-8.4 per 1,000 patient-years) and after (58.7 per 1,000 patient-years; 95% CI, 44.5-75.5 per 1,000 patient-years) dialysis. There was no increase in the incidence of ulcers or amputations after beginning hemodialysis.


Quantum dynamics of vibrationally activated OH-CO reactant complexes.
A six-dimensional wave packet study of the unimolecular decay of vibrationally activated OH-CO reactant channel complexes is presented. The ab initio based Lakin-Troya-Schatz-Harding potential energy functions for the A' and A" states are employed. Good agreement with the experimental product distributions and lifetimes of Pond and Lester is found. We are able to confirm that complexes with two vibrational quanta of excitation in OH, vOH=2, and no vibrational excitation in CO, vCO=0, decay through two pathways. One pathway leads to products (vOH=1, vCO=0) with relatively high OH rotational energy and the other leads to products (vOH=1, vCO=1) with relatively low OH rotational energy. We also find that the lifetime of the A" state is less than the A' state and that there is a propensity for A" products.


Persistent papillomavirus type-31 and type-45 infections predict the progression to squamous intraepithelial lesion.
Human papillomavirus (HPV) has been recognized as the major etiologic agent of cervical squamous cell carcinoma. However, it has been demonstrated that HPV infection is usually a self-limited process and does not lead to significant epithelial lesions or cancer. Recent data indicate that persistent high-risk HPV (HR-HPV) infections have a significantly increased risk of developing incident high-grade cervical intraepithelial neoplasia and cervical cancer. Our aim, therefore, was to assess whether there exist HPV genotypes whose persistence can be considered powerful surrogates of a progressive disease. We retrospectively selected all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance, with a positive test for HR-HPV, different from HPV types 16 and 18, and assessed the significance of the risk of progression based on the persistence of the specific HR-HPV. We retrospectively queried the database of our Colposcopy Clinic for all patients with a negative cytological diagnosis or with atypical squamous cells of undetermined significance and a positive test for HR-HPV, and we calculated the incidence of progression to lesions greater than or equal to low-grade squamous intraepithelial lesions after 6 months, according to the HPV type. A progression rate of 48.27% was found in patients tested positive for HPV-31 (Group 1), 38.46% in patients tested positive for HPV-45 (Group 2), and 5.73% in patients tested positive for HPV types other than HPV-16, HPV-18, HPV-31, and HPV-45 (Group 3). Our data demonstrate that the persistence of HPV-31 and HPV-45 is strongly associated with the occurrence of squamous intraepithelial lesion.


The infant feeding methods promoted by South African Instagram influencers in relation to crying and sleeping, 2018-2020: a retrospective digital ethnography.
Globally, there has been a decline in breastfeeding rates. This has resulted in increased infant mortality due to infectious diseases and inappropriate feeding practices. The aggressive marketing of breastmilk substitutes (BMS) by manufacturers has contributed, in part, to these declines. With the progressive use of social media, marketing has shifted from traditional methods to the use of influencers, who command a huge following on their social media accounts and influence the daily decisions of their followers. This study investigates the infant feeding methods and associated products promoted by South African influencers in relation to crying and sleeping and their followers' responses. This was a retrospective study, which used a mixed methods digital ethnographic approach to analyse posts related to infant feeding methods that were made by seven South African Instagram influencers between the period of January 2018 to December 2020. Framing analysis was used to analyse qualitative data and quantitative data were analysed descriptively. From the 62 posts that were analysed, 27 were sponsored advertisements (some violating local regulations) and 35 posts promoted breastfeeding. The 18,333 follower comments and 918,299 likes in response to the posts were also analysed. We found that influencers presented BMS products as a solution for a child who cries a lot and has trouble sleeping. BMS were framed as helpful for children who are seemingly always hungry and dissatisfied with breastmilk alone. The study also found that some influencers promoted breastfeeding on their Instagram pages. Unlike BMS posts, breastfeeding posts were not sponsored. With a few exceptions, followers tended to support and reinforce the framing of influencers. Stiffer regulations should be enforced against companies using influencers to promote infant formula and other BMS products, with proactive monitoring of social media. Professionals giving advice contrary to the guidelines from the WHO should be reported according to Regulation 991 and made accountable. Proactive engagement with Instagram influencers to promote breastfeeding should be considered.


Clinical pharmacology of inodilators.
Recent advances in our knowledge of heart failure have shown that both a central and a peripheral factor are involved in this syndrome. Therefore, the ideal drug should combine the properties of a positive inotropic agent with those of a peripheral vasodilator; many drugs recently introduced into clinical practice have been shown to present both of these features, and the term "inodilators" has been used to characterize them. Inodilators can be further classified on the basis of their mechanism of action, i.e., phosphodiesterase inhibitors, and sympathomimetic and dopaminergic drugs. Phosphodiesterase inhibitors include bipyridine, imidazolone, and benzimidazole derivatives, which present potent inotropic and vasodilatatory actions. Despite their favorable acute effects, long-term studies have often yielded controversial, and sometimes disappointing, results as their chronic administration seems often to be associated with untoward effects and, above all, a poor prognosis. Sympathomimetic agonists act by stimulation of beta-receptors, with a consequent increase of myocardial contractility and peripheral vasodilation. Differently from the parenteral drugs (e.g., dobutamine), the oral agents present many important shortcomings including central nervous system effects, increased myocardial oxygen consumption, tachyarrhythmias, and, above all, development of tolerance during chronic administration. Dopaminergic drugs possess a unique pharmacologic profile since they add to the adrenergic stimulation their selective action on dopaminergic receptors. Dopamine is still one of the most useful drugs for the treatment of acute heart failure; the two oral drugs that more closely resemble its actions are levodopa and ibopamine. The administration of levodopa to patients with heart failure can induce a significant hemodynamic improvement that is maintained during chronic therapy. Ibopamine has been widely shown to cause a significant hemodynamic improvement in patients with heart failure. Its effects can be ascribed to a moderate increase of myocardial contractility accompanied by peripheral and renal vasodilatatory actions. This drug can also counteract some of the neurohumoral mechanisms (e.g., sympathetic stimulation and aldosterone secretion) that are activated in heart failure. These features can explain the favorable results that have also been recently obtained after the chronic administration of ibopamine.


The nature of hospital-HMO affiliations.
Understanding the nature of hospital-HMO affiliations has implications for health care managers. A national survey of hospitals examined this nature, analyzing the extent of discounting , the relations between hospitals and HMOs and the payment mechanisms employed.


[PMMA lens implantation in sutureless corneal cataract surgery].
Self-sealing corneal cataract procedures have been known since 1992 and are recommended for foldable silicon lenses. Our goal was a technical modification without refractive disadvantages, which would also allow for the implantation of more rigid, but less expensive PMMA lenses of high optical quality. The "scleral stretch incision" by Freeman (1991) was applied to the corneal situation by widening the inner wound lip up to 6.5 mm; this makes it possible to implant a 5 mm optic through an outer wound opening of 4-4.2 mm. This method has been used since October 1992 on 980 patients, whereby the lamellar corneal incision was placed 1.5-1.8 mm deep to compensate for the astigmatism, if possible in the steeper meridian. The first 107 cases were followed up for longer than 6 months; they showed a surgically induced astigmatism of 1.18 +/- 0.79 D and a postoperative astigmatism of 0.86 +/- 0.70 D. Neither postoperative infection nor hypotony was observed in any of the cases. The modified corneal tunnel incision is recommended for 5 mm PMMA lenses; this is especially suited for cases of low to midgrade preoperative astigmatism that can be optimally improved by this procedure. In cases of pure spheric refraction, a 3 to 3.5 mm incision with foldable lens implantation is preferred.


Therapeutic targeting of cytokines.
Over recent years, with many advances in understanding the pathological processes that underlie many inflammatory conditions, it has become clear that targeting cytokines has proven to be highly effective therapeutically. The second International Cytokine symposium, held recently in Manchester UK, has provided an important forum for bringing basic and clinical scientists together to discuss many aspects of cytokine medicine from the laboratory to the clinic. In this article, we provide an overview of the main issues raised from this important conference and set the scene for more detailed reports that follow in subsequent articles in this journal.


Oral Kaposi Sarcoma in HIV-seronegative Saudi patient: Literature review and case report.
Kaposi Sarcoma (KS) is an intermediate neoplasm affecting the endothelial cells of mucous membranes and skin. It arises most commonly among HIV-infected individuals. We present an intra-oral KS in an 80-year-old Saudi male patient, who is HIV-seronegative, non-immunosuppressed, and with no history of organ transplantation. The patient was treated with fractionated radiation therapy, and had no recurrence in the 48 months of follow-up. The clinical disease, histologic features, and treatment modality used, as well as the relative literature are presented in this paper.


Optimization and validation of a plaque reduction neutralization test for the detection of neutralizing antibodies to four serotypes of dengue virus used in support of dengue vaccine development.
A dengue plaque reduction neutralization test (PRNT) to measure dengue serotype-specific neutralizing antibodies for all four virus serotypes was developed, optimized, and validated in accordance with guidelines for validation of bioanalytical test methods using human serum samples from dengue-infected persons and persons receiving a dengue vaccine candidate. Production and characterization of dengue challenge viruses used in the assay was standardized. Once virus stocks were characterized, the dengue PRNT(50) for each of the four serotypes was optimized according to a factorial design of experiments approach for critical test parameters, including days of cell seeding before testing, percentage of overlay carboxymethylcellulose medium, and days of incubation post-infection to generate a robust assay. The PRNT(50) was then validated and demonstrated to be suitable to detect and measure dengue serotype-specific neutralizing antibodies in human serum samples with acceptable intra-assay and inter-assay precision, accuracy/dilutability, specificity, and with a lower limit of quantitation of 10.


Physics behind the oscillation of pressure tensor autocorrelation function for nanocolloidal dispersions.
In this work, extensive equilibrium molecular dynamics simulations are conducted to explore the physics behind the oscillation of pressure tensor autocorrelation function (PTACF) for nanocolloidal dispersions, which leads to strong instability in viscosity calculation. By reducing the particle size and density, we find the intensity of the oscillation decreases while the frequency of the oscillation becomes higher. Careful analysis of the relationship between the oscillation and nanoparticle characteristics reveals that the stress wave scattering/reflection at the particle-liquid interface plays a critical role in PTACF oscillation while the Brownian motion/vibration of solid particles has little effect. Our modeling proves that it is practical to eliminate the PTACF oscillation through suppressing the acoustic mismatch at the solid-liquid interface by designing special nanoparticle materials. It is also found when the particle size is comparable with the wavelength of the stress wave, diffraction of stress wave happens at the interface. Such effect substantially reduces the PTACF oscillation and improves the stability of viscosity calculation.


Enter the dragon--China's journey to the hearing world.
China's population of 1.3 billion represents nearly 20% of the world's population. The current live birth rate in China is 17 million per year, compared with 4.1 million in the USA in 2009. Ministry of Health figures from China identify 115,000 children under the age of 7 years with severe-to-profound deafness and 30,000 babies born each year with hearing impairment. Universal Newborn Hearing Screening (UNHS) has been implemented in China since 1999. By 2010 UNHS was implemented in 20 of the 32 Chinese provinces. In large cities 95% of babies are screened in hospital-based programs. In more remote areas babies with high-risk factors for hearing loss are referred to screening centers within 1 month of birth and leaflets about identifying deafness are distributed. Since 1995 more than 10,000 people in China have received cochlear implants (CIs) and 85% of these implant recipients have been children under the age of 7 years. FINANCING OF CIs: China is in the process of developing a national reimbursement scheme for medical care. The first multichannel implant was performed in 1995. In 2005, a private financier provided more than 1500 implants for children under the age of 5 years. In 2009, the Chinese government set up a project to implant 1500 children aged 1-5 years over the next 3 years, with provision of the equivalent of US$65.4 million to pay for the devices, surgery, mapping, and rehabilitation. By 2011, the government had agreed to fund implants for an additional 17,000 children over 4 years. Schemes have been developed to train surgeons, Audiologists, and those involved in rehabilitation of implanted children in China. Standardized outcome tests are being developed for CI recipients. There are two large-scale ongoing outcome studies in progress. CI penetration in China is currently less than 5% of potential pediatric candidates, but cochlear implantation is continuing to expand at great speed, and it is hoped that the infrastructure and capacity will continue to grow and develop.


Aryl derivatives of 3H-1,2-benzoxaphosphepine 2-oxides as inhibitors of cancer-related carbonic anhydrase isoforms IX and XII.
A range of 3H-1,2-benzoxaphosphepine 2-oxide aryl derivatives with various substitution patterns at positions 7, 8, or 9 of the scaffold was synthesised in five steps from the commercially available salicylaldehydes. All of the newly obtained compounds were studied for their inhibition potency against carbonic anhydrase (CA) isoforms I, II, IX, and XII. Delightfully, these compounds showed a striking selectivity for the cancer-associated CA IX and XII over the cytosolic CA I and II, whose inhibition may lead to side-effects. Overall, a structure-activity relationship (SAR) revealed that 7- and 8-substituted aryl derivatives were more effective inhibitors of CA IX and XII than 9-substituted derivatives. In addition, the fluorine-containing analogues emerged as the most potent CA IX/XII inhibitors in this series.


Design and Analysis of a Low-Cost Electronically Controlled Mobile Ventilator, Incorporating Mechanized AMBU Bag, for Patients during COVID-19 Pandemic.
The outbreak of novel COVID-19 has severely and unprecedentedly affected millions of people across the globe. The painful respiratory distress caused during this disease calls for external assistance to the victims in the form of ventilation. The most common types of artificial ventilating units available at the healthcare facilities and hospitals are exorbitantly expensive to manufacture, and their number is fairly inadequate even in the so-called developed countries to cater to the burning needs of an ever-increasing number of ailing human subjects. According to available reports, without the provision of ventilation, the novel COVID-19 patients are succumbing to their ailments in a huge number of cases. This colossal problem of the availability of ventilator units can be addressed to a great extent by readily producible and cost-effective ventilating units that can be used on those suffering patients during an acute emergency and in the absence of conventional expensive ventilators at hospitals and medical care units. This paper has made an attempt to design and simulate a simple, yet effective, mechanized ventilator unit, which can be conveniently assembled without a profuse skillset and operated to resuscitate an ailing human patient. The stepper motor-controlled kinematic linkage is designed to deliver the patient with a necessitated discharge of air at optimum oxygen saturation through the AMBU bag connected in a ventilation circuit. With the associated code on MATLAB, the motor control parameters such as angular displacement and speed are deduced according to the input patient conditions (age group, tidal volume, breathing rate, etc.) and thereafter fed to the controller that drives the stepper motor. With a proposed feedback loop, the real-time static and dynamic compliance, airway resistance values can be approximately determined from the pressure variation cycle and fed to the controller unit to adjust the tidal volume as and when necessary. The simplistic yet robust design not only renders easy manufacturability by conventional and rapid prototyping techniques like 3D printing at different scales but also makes the product easily portable with minimal handling difficulty. Keeping the motto of Health for All as envisioned by the WHO, this low-cost indigenously engineered ventilator will definitely help the poor and afflicted towards their right to health and will help the medical professionals buy some time to manage the patient with acute respiratory distress syndrome (ARDS) towards recovery. Moreover, this instrument mostly includes readily available functional units having standard specifications and can be considered as standard bought-out items.


Real-based Polarity-preserving Asymmetric Fourier Imaging (RepAFI).
We proposed and assessed a modified asymmetric Fourier imaging (AFI) technique named real-based polarity-preserving AFI (RepAFI), in which the low-pass filter kernel for background phase estimation in AFI is optimized to preserve the magnetization polarity information for blood vessels and cerebrospinal fluid (CSF) even for data obtained using phase-sensitive inversion-recovery spin-echo-based (PSIR-SE) sequences with asymmetrical sampling in the k-space. Our proposed RepAFI technique achieves a practical balance of image quality and simplicity to provide better performance than conventional AFI methods.


Direct care workers' experiences of grief and needs for support.
A paucity of information is available on direct care workers' (DCWs') experiences with loss when their clients (people with intellectual and developmental disabilities [I/DD]) die. This study explored DCWs' grief experiences, their coping methods and their needs for support. A thematic analysis approach was used to examine data from nine focus groups with 60 DCWs from five community-based organizations that provide services to people with I/DD. Three themes (factors affecting DCW loss, ways that DCWs cope with loss and organizational issues affecting the bereavement experience) and associated subthemes emerged from the data. This highlighted not only DCW professional grief experiences but how organizational communication and policy affected their grief experience. DCWs experience grief in the workplace but may receive insufficient organizational bereavement supports. Recommendations are made for organizational policies and resources to improve organizational communication and assist DCWs in coping with their grief.


A Rare Case of Osteomyelitis Caused by Haemophilus Parainfluenzae.
Haemophilus parainfluenzae is a rare cause of bone and joint infections. We report a case of calcaneal osteomyelitis due to this microorganism with a review of all published. A 23-year-old woman presented with a 1-month history of pain and inflammation in the calcaneus area. Osteomyelitis was suspected at this location based on computed tomography images. Culture of six bone biopsies and surrounding tissue resulted in the isolation of H. parainfluenzae. Surgical drainage and debridement was performed, and antibiotic treatment was prescribed, resolving the infection.


Soft, comfortable polymer dry electrodes for high quality ECG and EEG recording.
Conventional gel electrodes are widely used for biopotential measurements, despite important drawbacks such as skin irritation, long set-up time and uncomfortable removal. Recently introduced dry electrodes with rigid metal pins overcome most of these problems; however, their rigidity causes discomfort and pain. This paper presents dry electrodes offering high user comfort, since they are fabricated from EPDM rubber containing various additives for optimum conductivity, flexibility and ease of fabrication. The electrode impedance is measured on phantoms and human skin. After optimization of the polymer composition, the skin-electrode impedance is only ~10 times larger than that of gel electrodes. Therefore, these electrodes are directly capable of recording strong biopotential signals such as ECG while for low-amplitude signals such as EEG, the electrodes need to be coupled with an active circuit. EEG recordings using active polymer electrodes connected to a clinical EEG system show very promising results: alpha waves can be clearly observed when subjects close their eyes, and correlation and coherence analyses reveal high similarity between dry and gel electrode signals. Moreover, all subjects reported that our polymer electrodes did not cause discomfort. Hence, the polymer-based dry electrodes are promising alternatives to either rigid dry electrodes or conventional gel electrodes.


The treatment of scoliosis in Duchenne muscular dystrophy.
There are not, as yet, clear indications for the surgical management of scoliosis in Duchenne muscular dystrophy (DMD), taking into account the varying severity of the clinical course. Monitoring the vital capacity can be most important for the indication and timing of surgery. In some cases, delaying surgical intervention with conservative management using spinal braces and wheelchair inserts can permit the restrictive lung syndrome to advance to the point that surgery will be contraindicated. Ten such patients conservatively treated for an average of 5 years exhibited perhaps a slower progression but ultimately an advanced deformity. From a second group of five carefully selected and surgically treated patients, indications for spinal surgery were reviewed. Surgical intervention should be prophylactically undertaken when there is high risk of a rapidly evolving curve with a severe restrictive lung syndrome.


Decomposing the dynamics of the Lorenz 1963 model using unstable periodic orbits: Averages, transitions, and quasi-invariant sets.
Unstable periodic orbits (UPOs) are a valuable tool for studying chaotic dynamical systems, as they allow one to distill their dynamical structure. We consider here the Lorenz 1963 model with the classic parameters' value. We investigate how a chaotic trajectory can be approximated using a complete set of UPOs up to symbolic dynamics' period 14. At each instant, we rank the UPOs according to their proximity to the position of the orbit in the phase space. We study this process from two different perspectives. First, we find that longer period UPOs overwhelmingly provide the best local approximation to the trajectory. Second, we construct a finite-state Markov chain by studying the scattering of the orbit between the neighborhood of the various UPOs. Each UPO and its neighborhood are taken as a possible state of the system. Through the analysis of the subdominant eigenvectors of the corresponding stochastic matrix, we provide a different interpretation of the mixing processes occurring in the system by taking advantage of the concept of quasi-invariant sets.


Sociocultural and psychological factors in American Indian drug use: implications for treatment.
Use of alcohol and other drugs has been acknowledged as a serious problem among American Indian populations. This study was designed to 1) compare female and male American Indian substance users in residential treatment on psychological (self-esteem, depression, attributional style) and sociocultural (demographics, personal drug use history, family history, acculturation) variables, and 2) examine relationships of the psychological and sociocultural variables with program completion. Results showed that females experienced more family dysfunction (family members misuse of substances, and emotional, physical, and sexual abuse) than males. Both females and males showed positive change on the psychological measures from treatment entry to treatment completion. The factors predicting dropout before program completion were divorce, use of cocaine and depressants, and living in foster care as a child. Implications for prevention, intervention, and training of treatment service providers are discussed.


Automatic Quantification of Tumour Hypoxia From Multi-Modal Microscopy Images Using Weakly-Supervised Learning Methods.
In recently published clinical trial results, hypoxia-modified therapies have shown to provide more positive outcomes to cancer patients, compared with standard cancer treatments. The development and validation of these hypoxia-modified therapies depend on an effective way of measuring tumor hypoxia, but a standardized measurement is currently unavailable in clinical practice. Different types of manual measurements have been proposed in clinical research, but in this paper we focus on a recently published approach that quantifies the number and proportion of hypoxic regions using high resolution (immuno-)fluorescence (IF) and hematoxylin and eosin (HE) stained images of a histological specimen of a tumor. We introduce new machine learning-based methodologies to automate this measurement, where the main challenge is the fact that the clinical annotations available for training the proposed methodologies consist of the total number of normoxic, chronically hypoxic, and acutely hypoxic regions without any indication of their location in the image. Therefore, this represents a weakly-supervised structured output classification problem, where training is based on a high-order loss function formed by the norm of the difference between the manual and estimated annotations mentioned above. We propose four methodologies to solve this problem: 1) a naive method that uses a majority classifier applied on the nodes of a fixed grid placed over the input images; 2) a baseline method based on a structured output learning formulation that relies on a fixed grid placed over the input images; 3) an extension to this baseline based on a latent structured output learning formulation that uses a graph that is flexible in terms of the amount and positions of nodes; and 4) a pixel-wise labeling based on a fully-convolutional neural network. Using a data set of 89 weakly annotated pairs of IF and HE images from eight tumors, we show that the quantitative results of methods (3) and (4) above are equally competitive and superior to the naive (1) and baseline (2) methods. All proposed methodologies show high correlation values with respect to the clinical annotations.


Effects of genetic background and environmental novelty on wheel running as a rewarding behaviour in mice.
Recent studies suggest running wheel activity to be naturally rewarding and reinforcing; considering the shared neuro-behavioural characteristics with drug-induced reward situations, wheel running behaviour gains interest as a tool to study mechanisms underlying reward-sensitivity. Previously, we showed that wheel running has the potential to disrupt the daily organization of home cage behaviour in female C57BL/6 [de Visser L, van den Bos R, Spruijt BM. Automated home cage observations as a tool to measure the effects of wheel running on cage floor locomotion. Behav Brain Res 2005;160:382-8]. In the present study, we investigated the effects of novelty-induced stress on wheel running and its impact on home cage behaviour in male C57BL/6 and DBA/2 mice. Our aim was to determine whether wheel running may be used as a tool to study both genetic and environmentally induced differences in sensitivity to rewarding behaviour in mice. One group of male mice was placed in an automated home cage observation system for 2 weeks with a wheel integrated in the cage. A second group of mice was allowed to habituate to this cage for 1 week before a running wheel was introduced. Results showed a pronounced sensitising effect of novelty on the level of wheel running in C57Bl/6 mice but not in DBA mice. Overall levels of wheel running were higher in DBA/2 mice. Furthermore, wheel running affected circadian rhythmicity in DBA/2 mice but not in C57BL/6 mice. From these findings we tentatively suggest that wheel running behaviour could serve as a tool to study the interaction between genetic and environmental factors in sensitivity to rewarding behaviour in mice. As it is displayed spontaneously and easy to monitor, wheel running may be well suitable to be included in high-throughput phenotyping assays.


Effect of STAT3 decoy oligodeoxynucleotides mediated by ultrasound-targeted microbubbles combined with ultrasound on the growth of squamous cell carcinoma of the esophagus.
Effect of STAT3 decoy oligodeoxynucleotides (ODN) transduced by ultrasound microbubbles combined with ultrasound on the growth of esophageal squamous cell carcinoma and its mechanism were analyzed. EC9706 cells were cultured in vitro and divided into four groups: group E (ultrasound microbubble + ultrasound irradiation), group P (liposome + ultrasound irradiation), group C (ultrasound), and group CC (ultrasound microbubbles). Mutant ODNs were used in groups E and P and the control group was group EC and PC, respectively. Immunofluorescence assay and flow cytometry were used to detect the transfection efficiency of each group. MTT colorimetric assay was performed to analyze the inhibition rate in each group. The effect of STAT3 decoy ODN on the proliferation of esophageal squamous carcinoma cells was calculated. Revese transcription-quantitative PCR (RT-qPCR) and western blotting were performed to detect the expression of the STAT signaling pathway downstream of gene expression levels. The model of subcutaneous transplantation of nude mice was used to show the effect of different transfections and STAT3 decoy ODN on the weight and volume of the transplanted tumor in mice. The cell inhibition rate was higher in group E than in groups P (F=8.382, P<0.001) and CC (F=6.469, P<0.001). Compared with groups EC, PC and C, respectively, the mRNA expression of STAT3, bcl-xL and Cyclin D1 decreased in groups E, P and CC (F=5.328, P<0.001). The weight and volume of nude mice in groups E, P and CC exhibited an inhibitory effect on the weight and volume of nude mice. Ultrasound irradiation combined with ultrasound microbubbles is an effective transfection method. The transfection of STAT3 decoy ODN can significantly inhibit the activity of esophageal squamous cell carcinoma cells and enhance apoptosis of cells, which has potential clinical value.


Mediation Analysis of Hepatitis B and C in Relation to Hepatocellular Carcinoma Risk.
Hepatitis B and C viruses are well-established risk factors for hepatocellular carcinoma (HCC) but their coordinated etiologic mechanism remains unclear. We aimed to assess the mediation effect of the two viruses on HCC risk. We conducted a prospective cohort study in Taiwan (R.E.V.E.A.L.-Hepatitis B Virus study), which included 3,851 participants seropositive for hepatitis B surface antigen and 278 incident HCC cases. Serum samples at enrollment or follow-up were tested for seromarkers and viral load of hepatitis B (HBV) and C (HCV). Mediation analyses for HCC risk were performed using Cox proportional hazards and linear regression models. Among participants with chronic hepatitis B, the direct effect of anti-HCV serostatus (positive vs. negative) independent of HBV viral load was associated with increased risk of HCC with a hazard ratio (HR) of 2.5 (95% confidence interval [CI] = 1.7, 3.6), and the indirect effect mediated through suppressing HBV viral load decreased the HCC risk with an HR of 0.75 (95% CI = 0.67, 0.84). Opposite effects led to an attenuated marginal effect with an HR of 1.7 (95% CI = 1.2, 2.5). For an increase in HCV viral load from 800 to 404,000 IU/ml (minimum to median viral level), the HRs were 1.6 (95% CI = 1.2, 2.0) for the direct effect, 0.78 (95% CI = 0.72, 0.85) for the indirect effect, and 1.1 (95% CI = 0.89, 1.5) for the marginal effect. The results support a suppressive effect of HCV on HCC risk mediated through HBV viral load and an adverse direct effect.


Emission characteristics of polycyclic aromatic hydrocarbons from pyrolytic processing during dismantling of electronic wastes.
Two typical types of electronic waste (E-waste) were selected to investigate the emission characteristics of polycyclic aromatic hydrocarbons (PAHs) during pyrolytic processing, including emission factor, compositional profile, size distribution and gas-particle partitioning. The mean emission factors (EFs) of total PAHs were measured to be 2.77 ± 1.41 μg/g and 23.65 ± 14.52 μg/g for printed wiring boards and plastic casings, respectively, lower than those for coal combustion and biomass burning. Low molecular weight species were predominant in exhaust fumes, with overwhelming amounts of naphthalene (NAP) and phenanthrene (PHE) in the gaseous phase and particulate phase, respectively. The particle-size distribution exhibited the largest enrichment of total PAHs in finer particles less than 2.1 μm. Similarly, the distributions of individual species were dominated by finer particles. Most freshly emitted PAHs were liable to exist in particulate phase relative to gaseous phase. Based on the benzo[a]pyrene equivalent carcinogenic power, PAHs in particulate phase may have much stronger toxicity compared with those present in gaseous phase. The gas-particle partitioning behaviors of freshly emitted PAHs from pyrolytic processing of E-wastes were mainly regulated by absorption rather than adsorption, and the gas-particle partitioning did not reach equilibrium.


Detection by in situ hybridization and phenotypic characterization of cells expressing IL-6 mRNA in human stimulated blood.
IL-6 has manifold biologic functions in immune and inflammatory responses and is produced by a variety type of cells. In this work, we used the whole blood culture to identify the cells expressing IL-6 gene/protein after various stimulation. When the whole blood was incubated with LPS or Con A, much IL-6 activity, measured by the growth promoting assay using a murine IL-6-dependent hybridoma clone, was detected in the plasma as early as 4 h of culture and continued to increase with time, reaching a plateau around 12 h. Immunocytochemical analysis with anti-rIL-6 antiserum revealed that a proportion of mononuclear cells (MNC) contained intracytoplasmic IL-6 in LPS- or Con A-stimulated blood. Northern blot analysis for MNC from the blood stimulated with these stimuli showed that their transcripts for IL-6 peaked at 4 h, then rapidly declined and was undetectable after 24 h of stimulation. In situ hybridization technique with radiolabeled antisense RNA probe for IL-6 demonstrated that a fraction of MNC from LPS- as well as Con A-stimulated blood expressed IL-6 mRNA. With the combined use of in situ hybridization and immunofluorescence by corresponding mAb, it was confirmed that IL-6 mRNA expressing cells in stimulated blood were exclusively monocytes. In the whole blood culture, it was shown that expression of IL-6 mRNA by monocytes was inhibited by dexamethasone, but not by cyclosporin A. These results suggest that monocytes are the major cells expressing IL-6 gene/protein in the circulation after exposure to external stimuli.


Optimisation of glucose and levulinic acid production from the cellulose fraction of giant reed (Arundo donax L.) performed in the presence of ferric chloride under microwave heating.
A two-step exploitation of the giant reed cellulose to glucose and levulinic acid, after the complete removal of the hemicellulose fraction, was investigated using FeCl3 as catalyst. In the first step, the microwave-assisted hydrolysis of cellulose to glucose was optimised by response surface methodology analysis, considering the effect of temperature, reaction time and catalyst amount. Under the optimised reaction conditions, the glucose yield was 39.9 mol%. The cellulose-rich residue was also converted by enzymatic hydrolysis, achieving the glucose yield of 39.8 mol%. The exhausted residue deriving from the chemical hydrolysis was further converted to levulinic acid by microwave treatment at harsher reaction conditions. The maximum levulinic acid yield was 64.3 mol%. On the whole, this cascade approach ensured an extensive and sustainable exploitation of the C6 carbohydrates to glucose and levulinic acid, corresponding to about 70 mol% of glucan converted to these valuable bioproducts in the two steps.


The acidic region and conserved putative protein kinase C phosphorylation site in Nef are important for SIV replication in rhesus macaques.
Variants of the pathogenic SIVmac239 clone with changes in Nef were analyzed to assess the functional relevance of two highly conserved regions in Nef in vitro and in vivo. Changes in a region with an acidic charge (Aci-Nef), or a potential protein kinase C phosphorylation site (PKC-Nef), impaired the ability of Nef to down-regulate CD4 and MHC class I surface expression and to alter CD3-initiated signal transduction in Jurkat T cells. The Aci-Nef, but not the PKC-Nef, associated with the previously described p65 phosphoprotein. SIV containing Aci-Nef, but not SIV containing PKC-Nef, showed reduced infectivity and replication in cell culture systems. One of two rhesus macaques infected with the PKC-Nef mutant virus showed rapid reversion and progressed to disease. In the second animal no reversions and nonprogressive infection was observed. In one of two macaques infected with the Aci-Nef variant, the mutations were stable during the first 40 weeks after infection. Thereafter, variants evolved in which up to six of the eight mutated positions in Nef were reverted and functional activity in vitro was partially restored. These changes occurred concomitantly with increasing viral load and disease progression. The second animal infected with the Aci-Nef variant showed no reversions and remained asymptomatic. Our study suggests that the acidic region and conserved PKC phosphorylation site in Nef are important for SIV replication in rhesus macaques and for several in vitro Nef functions. An almost wild-type activity in in vitro infectivity and replication assays seems insufficient to confer a full nef-positive phenotype in vivo.


A phase II study of neoadjuvant combination chemotherapy with docetaxel, cisplatin, and S-1 for locally advanced resectable gastric cancer: nucleotide excision repair (NER) as potential chemoresistance marker.
The combination of docetaxel, cisplatin, and S-1 (DCS) chemotherapy is expected to be a promising regimen for advanced gastric cancer. This study was performed to evaluate the efficacy and safety of neoadjuvant DCS chemotherapy for locally advanced resectable gastric cancer. Patients with locally advanced gastric cancer received 2 courses of preoperative chemotherapy with S-1 (40 mg/m(2) b.i.d.) on days 1-14 and docetaxel (60 mg/m(2)) plus cisplatin (60 mg/m(2)) on day 8 every 3 weeks, followed by standard curative surgery within 4-8 weeks. The primary endpoint was R0 resectability. Expression of damage DNA binding protein complex subunit 2 (DDB2)/excision repair cross-complementing 1 (ERCC1) in the pretreated tumor tissues was examined by immunohistochemistry. A total of 43 patients received neoadjuvant chemotherapy. The response rate was 74.4%, and disease control ratio was 100%. Grade 4 neutropenia developed in 53.5% of patients and febrile neutropenia in 16.3%. Non-hematological grade 3/4 adverse events were anorexia (23.3%), nausea (14.0%), and diarrhea (23.3%), but these were generally transient and manageable. The proportion of R0 resections in the 43 eligible patients was 90.7%, and a pathological response was found in 65.9% of patients. There were no treatment-related deaths and no major surgical complications. The accuracy of the combination of DDB2 and ERCC1 expression for predicting chemoresistance was 82.5%. Preoperative treatment with DCS combination for locally advanced gastric cancer demonstrated a sufficient R0 resection rate and a good pathological response with manageable toxicities. The DDB2/ERCC1-high phenotype, as determined by immunohistochemistry, may be useful predictor of resistance to DCS chemotherapy.


Singlet oxygen-responsive micelles for enhanced photodynamic therapy.
Photodynamic therapy (PDT) efficacy is limited by the very short half-life and limited diffusion radius of singlet oxygen (1O2). We report a 1O2-responsive micellar nanoplatform subject to considerable size-expansion upon light triggering to facilitate on-demand release of photosensitizers. Imidazole, a well-known 1O2 scavenger, was incorporated in the hydrophobic core of amphiphilic copolymer micelles, and was used to coordinate with biocompatible Zn2+ and encapsulate the photosensitizer chlorin e6 (Ce6). The micelles are highly sensitive to light irradiation: 1O2 triggering induced dramatic particle size expansion due to the conversion of imidazole to hydrophilic urea, resulting in instantaneous release of Ce6 and rapid intracellular distribution. This 1O2-responsive, size-expandable nanosystem delivered substantially more Ce6 to tumor sites as compared to free Ce6, and exhibited improved anti-tumor efficacy in vivo in 4T1 tumor-bearing mice. This work opens new avenues of particle expansion-induced PDT enhancement by controlled imidazole chemistry.


A list of device-specific thresholds for the clinical interpretation of peripheral x-ray absorptiometry examinations.
The UK National Osteoporosis Society (NOS) has recently issued new guidelines on the use of peripheral x-ray absorptiometry (pDXA) devices in managing osteoporosis. The NOS guidelines recommend a triage approach in which patients' bone mineral density (BMD) measurements are interpreted using upper and lower thresholds specific to each type of pDXA device. The thresholds are defined so that patients with osteoporosis at the hip or spine are identified with 90% sensitivity and 90% specificity. Patients with a pDXA result below the lower threshold are likely to have osteoporosis at the hip or spine, patients with a result above the upper threshold are unlikely to have osteoporosis, while those between the two thresholds require a hip and spine BMD examination for a definitive diagnosis. This report presents data from a multicenter study to establish the triage thresholds for a range of pDXA devices in use in the UK. The subjects were white female patients aged 55-70 years who met the normal referral criteria for a BMD examination. For each device, at least 70 women with osteoporosis at the hip or spine and 70 women without osteoporosis were enrolled. All women had hip and spine BMD measurements using axial DXA systems that were interpreted using the National Health and Nutrition Examination Survey (NHANES) reference range for the hip and the manufacturers' reference ranges for the spine. Data are presented for five different devices: the Osteometer DTX-200 (forearm BMD), the Schick AccuDEXA (hand BMD), the GE Lunar PIXI (heel BMD), the Alara MetriScan (hand BMD), and the Demetech Calscan (heel BMD). The clinical measurements were supplemented by theoretical modeling to estimate the age dependence of the triage thresholds and the effect of the correlation coefficient between pDXA and axial BMD on the percentage of women referred for an axial BMD examination. In summary, this study provides thresholds for implementing the new NOS guidelines for managing osteoporosis using pDXA devices. The figures reported apply to postmenopausal white women aged 55-70 years who meet the conventional criteria for a BMD examination. The results confirm that the thresholds are specific to each type of pDXA device and that the NOS triage algorithm requires 40% of women to have an axial DXA examination.


[The HLA system and Coxsackie B viral myocarditis in adults].
The distribution of HLA antigens A, B and C was studied in 152 normal donors, 53 patients with Coxsackie B virus myocarditis, 35 patients with myocarditis of unknown origin, 16 coronary patients and 14 rheumatic patients with high titres of anti-Coxsackie virus antibodies. Coxsackie virus myocarditis was associated with increased occurrence of HLA antigens A3, B40, Cw2 and A28, the increase being significant (with an adjustment to the number of the tested antigens) for A3 in severe and medium myocarditis, and B40 in patients who had developed myocarditis before age 30. Antigen Cw2 was more common in myocarditis patients with high titres of anti-Coxsackie virus B4 antibodies. The distribution of HLA antigens in coronary patients was similar to that of the controls. Rheumatic patients showed increased incidence of antigen Cw2. It is suggested that carriers of histocompatibility antigen A3 may be predisposed genetically to severe or medium Coxsackie B virus myocarditis.


Qualitative case study of needle exchange programs in the Central Appalachian region of the United States.
The Central Appalachian region of the United States is in the midst of a hepatitis C virus epidemic driven by injection of opioids, particularly heroin, with contaminated syringes. In response to this epidemic, several needle exchange programs (NEP) have opened to provide clean needles and other supplies and services to people who inject drugs (PWID). However, no studies have investigated the barriers and facilitators to implementing, operating, and expanding NEPs in less populous areas of the United States. This qualitative case study consisted of interviews with program directors, police chiefs, law enforcement members, and PWID affiliated with two NEPs in the rural state of West Virginia. Interview transcripts were coded inductively and analyzed using qualitative data analysis software. Final common themes related to barriers and facilitators of past program openings, current program operations, and future program plans, were derived through a consensus of two data coders. Both NEPs struggled to find existing model programs, but benefited from broad community support that facilitated implementation. The largest operational barrier was the legal conundrum created by paraphernalia laws that criminalize syringe possession. However, both PWID and law enforcement appreciated the comprehensive services provided by these programs. Program location and transportation difficulties were additional noted barriers. Future program operations are threatened by funding shortages and bans, but necessitated by unexpected program demand. Despite broad community support, program operations are threatened by growing participant volumes, funding shortages, and the federal government's prohibition on the use of funds to purchase needles. Paraphernalia laws create a legal conundrum in the form of criminal sanctions for the possession of needles, which may inadvertently promote needle sharing and disease transmission. Future studies should examine additional barriers to using clean needles provided by rural NEPs that may blunt the effectiveness of NEPs in preventing disease transmission.


Oxidation of methionine 216 in sheep and elk prion protein is highly dependent upon the amino acid at position 218 but is not important for prion propagation.
We employed a sensitive mass spectrometry-based method to deconstruct, confirm, and quantitate the prions present in elk naturally infected with chronic wasting disease and sheep naturally infected with scrapie. We used this approach to study the oxidation of a methionine at position 216 (Met216), because this oxidation (MetSO216) has been implicated in prion formation. Three polymorphisms (Ile218, Val218, and Thr218) of sheep recombinant prion protein were prepared. Our analysis showed the novel result that the proportion of MetSO216 was highly dependent upon the amino acid residue at position 218 (I > V > T), indicating that Ile218 in sheep and elk prion protein (PrP) renders the Met216 intrinsically more susceptible to oxidation than the Val218 or Thr218 analogue. We were able to quantitate the prions in the attomole range. The presence of prions was verified by the detection of two confirmatory peptides: GENFTETDIK (sheep and elk) and ESQAYYQR (sheep) or ESEAYYQR (elk). This approach required much smaller amounts of tissue (600 μg) than traditional methods of detection (enzyme-linked immunosorbent assay, Western blot, and immunohistochemical analysis) (60 mg). In sheep and elk, a normal cellular prion protein containing MetSO216 is not actively recruited and converted to prions, although we observed that this Met216 is intrinsically more susceptible to oxidation.


Reliability and Validity of 3 Methods of Assessing Orthopedic Resident Skill in Shoulder Surgery.
Traditional measures for evaluating resident surgical technical skills (e.g., case logs) assess operative volume but not level of surgical proficiency. Our goal was to compare the reliability and validity of 3 tools for measuring surgical skill among orthopedic residents when performing 3 open surgical approaches to the shoulder. A total of 23 residents at different stages of their surgical training were tested for technical skill pertaining to 3 shoulder surgical approaches using the following measures: Objective Structured Assessment of Technical Skills (OSATS) checklists, the Global Rating Scale (GRS), and a final pass/fail assessment determined by 3 upper extremity surgeons. Adverse events were recorded. The Cronbach α coefficient was used to assess reliability of the OSATS checklists and GRS scores. Interrater reliability was calculated with intraclass correlation coefficients. Correlations among OSATS checklist scores, GRS scores, and pass/fail assessment were calculated with Spearman ρ. Validity of OSATS checklists was determined using analysis of variance with postgraduate year (PGY) as a between-subjects factor. Significance was set at p < 0.05 for all tests. Criterion validity was shown between the OSATS checklists and GRS for the 3 open shoulder approaches. Checklist scores showed superior interrater reliability compared with GRS and subjective pass/fail measurements. GRS scores were positively correlated across training years. The incidence of adverse events was significantly higher among PGY-1 and PGY-2 residents compared with more experienced residents. OSATS checklists are a valid and reliable assessment of technical skills across 3 surgical shoulder approaches. However, checklist scores do not measure quality of technique. Documenting adverse events is necessary to assess quality of technique and ultimate pass/fail status. Multiple methods of assessing surgical skill should be considered when evaluating orthopedic resident surgical performance.


Crimean-Congo Hemorrhagic Fever Virus and Borrelia burgdorferi sensu lato in Ticks from Kosovo and Albania.
Tick-borne diseases pose a serious threat to human health in South-Eastern Europe, including Kosovo. While Crimean-Congo hemorrhagic fever (CCHF) is a well-known emerging infection in this area, there are no accurate data on Lyme borreliosis and tick-borne encephalitis (TBE). Therefore, we sampled and tested 795 ticks. Ixodes ricinus (n = 218), Dermacentor marginatus (n = 98), and Haemaphysalis spp. (n = 24) were collected from the environment by flagging (all from Kosovo), while Hyalomma marginatum (n = 199 from Kosovo, all from Kosovo) and Rhipicephalus bursa (n = 130, 126 from Albania) could be collected only by removal from animal pasture and domestic ruminants. Ticks were collected in the years 2014/2015 and tested for viral RNA of CCHF and TBE viruses, as well as for DNA of Borrelia burgdorferi sensu lato by real-time PCR. In Kosovo, nine ticks were positive for RNA of Crimean-Congo hemorrhagic fever virus and seven for DNA of B. burgdorferi s. l. None of the ticks tested positive for TBEV. CCHF virus was detected in one H. marginatum male specimen collected while feeding on grazing cattle from the Prizren region and in eight R. bursa specimens (five females and three males collected while feeding on grazing sheep and cattle) from the Prishtina region (Kosovo). B. burgdorferi s. l. was detected in seven questing ticks (four male and one female D. marginatus, two I. ricinus one female and one male) from the Mitrovica region (Kosovo). Our study confirmed that CCHF virus is circulating in Kosovo mainly in H. marginatum and R. bursa in the central areas of the country. B. burgdorferi s. l. was found in its major European host tick, I. ricinus, but also in D. marginatus, in the north of the Kosovo. In order to prevent the spread of these diseases and better control of the tick-borne infections, an improved vector surveillance and testing of ticks for the presence of pathogens needs to be established.


The application of a masked orbiting transmission source for attenuation correction in PET.
A new technique for attenuation correction in positron emission tomography is introduced and evaluated. Transmission scans are performed with a point source of 68Ge encapsulated in a lead collimator that masks the source into a fan beam in the scanning plane. The source orbits the patient section at the edge of the slice defining collimator. Only events acquired by detector pairs that are collinear with the source are used to calculate the attenuation coefficients. Events from detector pairs that are nearly collinear are rejected, while those from detector pairs that are far from collinear may be used to acquire a simultaneous emission scan. The coincident event rate per unit source activity is over twice that of rod and ring sources. This technique is compared with calculated outline and ring source attenuation correction techniques in a pie phantom. The linear attenuation coefficient for water was measured as 0.096 cm-1, and 0.094 cm-1 when the water contained 12 kBq/cc 68Ga, compared with 0.085 cm-1 for a ring source. Cerebral glucose utilization rates in a normal volunteer reconstructed with transmission scans performed pre- and postinjection of fluorodeoxyglucose show no significant differences. However, values of cortical glucose utilization average 12% above those measured with the fitted outline method in the highest cuts because of the obliqueness of the skull to the planes examined.


Hemodynamic and gas exchange responses to infusion of acetylcholine and inhalation of nitric oxide in patients with chronic obstructive lung disease and pulmonary hypertension.
To investigate endothelium-dependent and endothelium-independent nitric oxide (NO) mediated pulmonary vasodilation in patients with chronic obstructive lung disease (COLD), we examined the responses to incremental infusion rates of acetylcholine (ACh) or inhaled NO on hemodynamic and gas exchange. In 13 patients, ACh (15 mg/min) decreased pulmonary artery pressure (Ppa) from 31 +/- 1 to 28 +/- 1 mm Hg (p < 0.01) and systemic arterial pressure while increasing cardiac index from 3.7 +/- 0.4 to 4.7 +/- 0.4 L/min/m2 (p < 0.01). Inhaling 40 parts per million (ppm) NO decreased Ppa from 32 +/- 1 to 26 +/- 1 mm Hg (p < 0.001) with no associated hemodynamic change. ACh reduced PaO2 from 57 +/- 3 to 48 +/- 2 mm Hg (p < 0.01) and increased venous admixture (QVA/QT) from 35 +/- 3 to 45 +/- 3% (p < 0.01). Inhaling 40 ppm NO increased PaO2 from 57 +/- 3 to 60 +/- 3 mm Hg (p < 0.01) and decreased QVA/QT from 36 +/- 3 to 32 +/- 3% (p < 0.01). Pulmonary vascular resistance changes were similar in response to 40 ppm NO or 15 mg/min ACh. In COLD patients, ACh produces both pulmonary and systemic vasodilation but impairs arterial oxygenation whereas inhaled NO induces selective pulmonary vasodilation while improving gas exchange. The resistance to ACh in some patients could be related to pulmonary endothelial dysfunction.


A case of life-threatening acute kidney injury with toxic encephalopathy caused by Dioscorea quinqueloba.
Some herbal medications induce acute kidney injury. The acute kidney injuries caused by herbal medications are mild and commonly treated by palliative care. A 51-years-old man who drank the juice squeezed from the raw tubers of Dioscorea quinqueloba (D. quinqueloba) was admitted with nausea, vomiting and chilling. He developed a seizure with decreased level of consciousness. He was diagnosed with acute kidney injury, which was cured by continuous venovenous hemodialfiltration. Non-detoxified D. quinqueloba can cause severe acute kidney injury with toxic encephalopathy. It is critical to inform possible adverse effects of the medicinal herbs and to implement more strict regulation of these products.


Lateralizing sensorimotor deficits in a case of pseudopheochromocytoma.
Pseudopheochromocytoma is a poorly understood, rare cause of severe paroxysmal hypertension that mimics the symptomatology of pheochromocytoma in the absence of biochemical evidence of this tumor. Symptoms such as headache, nausea, sweating, and palpitations during hypertensive episodes have been described. In this paper, we describe previously unreported findings of lateralizing sensorimotor deficits in a patient with pseudopheochromocytoma. These changes presented during a hypertensive episode and were concerning for stroke but were not accompanied by acute radiologic abnormalities. The deficits improved over 1.5 weeks as blood pressure stabilized with beta-blockade. We also review relevant literature on the clinical features, pathophysiology, and management of pseudopheochromocytoma.


Presence of Borrelia in different populations of Ixodes pararicinus from northwestern Argentina.
This work was performed to evaluate the presence of Borrelia in different populations of Ixodes pararicinus from northwestern Argentina (Jujuy, Salta and Tucumán provinces). Questing adults and nymphs of I. pararicinus were collected from vegetation, and I. pararicinus nymphs were also collected on birds. Eighty-two ticks were tested for Borrelia presence by PCR targeting the gene flagellin and the rrfA-rrlB intergenic spacer region. Pools of ticks positive to Borrelia were formed by two nymphs collected on Turdus rufiventris in Tucumán, one nymph collected on Syndactyla rufosuperciliata in Jujuy, one nymph collected on Turdus nigriceps in Tucumán, three nymphs collected on T. nigriceps in Tucumán, and two females collected from vegetation in Salta. Two haplotypes of Borrelia sp. belonging to the Borrelia burgdorferi sensu lato complex were found. One of them is closely related to the haplotypes of Borrelia genospecies previously reported in I. aragaoi from Uruguay (haplotypes D and E) and in I. pararicinus from Jujuy Province in Argentina. The second haplotype (detected in the sample of Salta) is closely related to the haplotypes A, B and C associated with I. aragaoi from Uruguay. All these results suggest that the presence of B. burgdorferi s.l. genospecies in I. pararicinus ticks is widespread along the entire distribution of this tick species in northwestern Argentina. However, the Borrelia presence in I. pararicinus cannot be directly assumed as a phenomenon of medical relevance, because Ixodes ticks are not relevant as human parasites in South America, and none of the two Borrelia genospecies detected in this work is related to any of the Borrelia genospecies currently known to be pathogenic to humans.