"I can't just follow any particular textbook": immigrants in cardiac rehabilitation.
The study purpose was to examine how and under what circumstances immigrants combine diabetes self-care with cardiac rehabilitation recommendations. Cardiac rehabilitation can improve and lengthen life in people with coronary heart disease as it promotes healthy physical and psychosocial behaviours and outcomes. This study is the first to examine the convergence of two common issues on participation: (1) the problems posed when cardiac rehabilitation patients must also contend with type II diabetes and (2) the experiences of immigrants in cardiac rehabilitation. A critical ethnographic approach was employed. Two in depth interviews were conducted with 18 immigrants (eight men, ten women) enrolled in cardiac rehabilitation. Data were collected from 2008-2010. Threaded throughout immigrant participants' descriptions were biographical accounts of crossing geographical borders, establishing a sense of belonging in their adopted country and trying to feel 'at home' in cardiac rehabilitation. Participants described creative hybridization of transnationally informed knowledges and particularized practices to manage diabetes self-care and to reduce cardiac risk. Participants judiciously considered, assessed and blended knowledges from cardiac rehabilitation, experience with their own bodies and general 'wisdoms' passed on within their own and other immigrant communities. These findings suggest that migration constitutes an important social positioning that contextualizes individual efforts to activate diabetes self-care and cardiac rehabilitation. Support to immigrants may improve when nurses recognize the significance of such experiences. Efforts are needed in practice and research to recognize and explore immigrants' creative efforts to engage in cardiac rehabilitation.


Surgical resection for advanced bisphosphonate-related osteonecrosis of the jaw associated with fibrous dysplasia: a case report.
Bisphosphonate-related osteonecrosis of the jaw (BRONJ) is an adverse drug reaction represented by destruction and/or death of bone. Fibrous dysplasia (FD) is a rare bony disorder characterised by abnormal fibro-osseous tissue that has lowered resistance to infection. Effective treatments for BRONJ that follows FD are unclear. Here, we report that advanced BRONJ associated with FD was successfully treated by surgical resection. A 69-year-old woman, whose left maxillary bone showed a ground glass appearance on computed tomography (CT) images, was taking alendronate. At 1 year after teeth within the abnormal bone were extracted, exposed bone was observed in the extraction sites and CT images revealed separated sequestrums. Under the clinical diagnosis of Stage 2 BRONJ with FD, we performed not only sequestrectomy but also a partial resection of the FD. Thereafter, the healing was uneventful without recurrence. In conclusion, our case suggests that surgical resection is useful for advanced BRONJ associated with FD.


Effects of foliar application of zinc sulfate and zinc nanoparticles in coffee (Coffea arabica L.) plants.
A greenhouse study comparing the physiological responses and uptake of coffee (Coffea arabica L.) plants to foliar applications of zinc sulfate (ZnSO4) and zinc nano-fertilizer (ZnO NPs) was conducted with the aim to understand their effects on plant physiology. One-year old coffee plants were grown in greenhouse conditions and treated with two foliar applications of 10 mg/L of Zn as either zinc sulfate monohydrate (ZnSO4 ‧ H2O) or zinc oxide nanoparticle (ZnO NPs 20% w/t) and compared to untreated control plants over the course of 45 days. ZnO NPs positively affected the fresh weight and dry weight (FW and DW) of roots and leaves, increasing the FW by 37% (root) and 95% (leaves) when compared to control. The DW increase was 28%, 85%, and 20% in roots, stems, and leaves, respectively. The net photosynthetic rate increased 55% in response to ZnO NPs treatment at the end of experiment when compared to control. ZnO NPs-treated leaves contained significantly higher amounts of Zn (1267.1 ± 367.2 mg/kg DW) when compared to ZnSO4-treated plants (344.1 ± 106.2 mg/kg DW), while control plants had the lowest Zn content in the leaf tissue (53.6 ± 18.9 mg/kg DW). X-ray micro-analyses maps demonstrated the increased penetrance of ZnO NPs in coffee leaf tissue. Overall, ZnO NPs had a more positive impact on coffee growth and physiology than conventional Zn salts, which was most likely due to their increased ability to be absorbed by the leaf. These results indicate that the application of ZnO NPs could be considered for coffee systems to improve fruit set and quality, especially in areas where Zn deficiency is high.


[Influence of history of oral bisphosphonates on the incidence rate of fever after intravenous injection of zoledronic acid in patients with osteoporosis].
To investigate the prevalence of fever after intravenous injection of for the first time in osteoporotic patients who have or haven't taken bisphosphonates orally. Bone mineral density measurement was conducted of the osteoporotic patients using dual-energy X-ray absorptiometry method, and according to the WHO diagnostic criteria for osteoporosis, the patient whose T score was less than -2.5 was defined as osteoporosis. The data of 113 osteoporotic patients who received intravenous injection of zoledronic acid in our hospital for the first time were used for analysis. Among them, 35 who had the history of oral bisphosphonates were defined as group A, and 78 who didn't have the history of oral bisphosphonates were defined as group B (control group). Moreover, we also compared the prevalences of fever between the patients. Pearson chi-square test was used to investigate the association between oral bisphosphonates therapy and prevalence of fever, and binary logistic regression was used to analyze the impact factors of fever after intravenous injection of zoledronic acid. Among the 35 patients who had the history of oral bisphosphonates, nobody had high fever, and 2 patients had low or moderate degree of fever (5.71%). Among the 78 patients who didn't have the history of oral bisphosphonates, 33 patients had fever (42.3%), 15 with low fever, and 14 with moderate degree of fever, and 4 with high fever. Pearson chi-square test showed that the prevalence of fever between group A and group B had significant difference, and that differences of prevalence of fever between the outpatients and the inpatients was not statistically significant. Binary Logistic regression analysis showed that oral bisphosphonates medication history was a protective factor of fever, and with the increasing of previous oral bisphosphonates for one month, there was a reduction of fever for 23.1%. Patients who have the history of oral nitrogenous bisphosphonates alendronate have a significant reduction in prevalence of fever after intravenous injection of zoledronic acid for the first time. That is, oral nitrogenous bisphosphonates alendronate history is a protective factor of fever for patients with intravenous injection of zoledronic acid for the first time.


The ethnic nose.
There are distinctive anatomical differences between the non-Caucasian (platyrrhine, mesorrhine) nose and the Caucasian (leptorrhine) nose. In general, non-Caucasian patients requesting aesthetic rhinoplasty desire improvement and refinement of their noses with preservation of defining ethnic characteristics. Surgeons who perform rhinoplasty in this patient population must be familiar with the variations in nasal anatomy and implement augmentation rather than reduction techniques to achieve the desired aesthetic and functional outcomes. We provide a brief review of recent historical trends in ethnic rhinoplasty, highlight relevant anatomical differences, and describe our strategy for addressing the challenges of ethnic rhinoplasty.


A Simplified Method To Create Quantitative, "Fixed" Uranyl-Contaminated Metal Coupons.
A method was developed and validated to quantitatively apply and "fix" uranyl contamination onto a metal surface (steel). Simple approaches are needed to create test surfaces in order to quantify contaminant removal or "decon" methods. We used steel discs sized to allow direct and accurate alpha counting in a Ludlum scanner from radioactive contaminants. A typical 3.8-cm-diameter coupon had a depleted uranyl loading of about 0.1 mg U cm with a count of 980 dpm. The resulting alpha radiation was measured with a precision of >97% for the same coupon. The alpha concentration on replicate coupons differed by as much as 9% (standard deviation). This method, based on earlier methods, required a uranyl solution to be dried but lowers the baking temperature to less than 100°C to increase safety in a typical radiological laboratory. A dike was used to provide a uniform coating of the uranyl solution.


Mitigating effect of tanshinone IIA on ventricular remodeling in rats with pressure overload-induced heart failure.
To investigate the effect of tanshinone IIA (TIIA) on ventricular remodeling in rats with pressure overload-induced heart failure. Pressure overload-induced heart failure model (abdominal aortic coarctation) was established in 40 rats, which were divided into model and 5, 10 and 20 mg/kg TIIA groups. Ten rats receiving laparotomy excepting abdominal aortic coarctation were enrolled in sham-operated group. The 5, 10 and 20 mg/kg TIIA groups were treated with 5, 10 and 20 mg/kg TIIA, respectively, for 8 weeks. Compared with model group, in 20 mg/kg TIIA group the left ventricular ejection fraction, left ventricular fractional shortening, left ventricular systolic pressure, ±maximum left ventricular pressure rising and dropping rate, and myocardial B-cell lymphoma-2 and cleaved cysteinyl aspartate specific proteinase-3 protein levels were increased, respectively (P<0.05), and the left ventricular end diastolic diameter, left ventricular end systolic diameter, left ventricular end diastolic pressure, heart weight index, left ventricular weight index, serum B-type brain natriuretic peptide, interleukin 6 and C-reactive protein levels and myocardial B-cell lymphoma-2 associated X protein level were decreased, respectively (P<0.05). TIIA may alleviate ventricular remodeling in rats with pressure overload-induced heart failure heart by reducing inflammatory response and cardiomyocyte apoptosis.


Microengineered perfusable 3D-bioprinted glioblastoma model for in vivo mimicry of tumor microenvironment.
Many drugs show promising results in laboratory research but eventually fail clinical trials. We hypothesize that one main reason for this translational gap is that current cancer models are inadequate. Most models lack the tumor-stroma interactions, which are essential for proper representation of cancer complexed biology. Therefore, we recapitulated the tumor heterogenic microenvironment by creating fibrin glioblastoma bioink consisting of patient-derived glioblastoma cells, astrocytes, and microglia. In addition, perfusable blood vessels were created using a sacrificial bioink coated with brain pericytes and endothelial cells. We observed similar growth curves, drug response, and genetic signature of glioblastoma cells grown in our 3D-bioink platform and in orthotopic cancer mouse models as opposed to 2D culture on rigid plastic plates. Our 3D-bioprinted model could be the basis for potentially replacing cell cultures and animal models as a powerful platform for rapid, reproducible, and robust target discovery; personalized therapy screening; and drug development.


Signing on to sign out, part 2: describing the success of a web-based patient sign-out application and how it will serve as a platform for an electronic discharge summary program.
Sunnybrook Health Sciences Centre developed and implemented a physician-focused web-based patient sign-out application in January of 2005 with 40 different groups throughout the hospital now using it. More groups are continuing to request access to the system, including nursing and other multidisciplinary groups. The success of the system is attributable to its simplicity and usability as there is rarely any downtime and no formal training for physicians is ever necessary. The next step is to create an electronic discharge summary program. Using an electronic system to complete discharge summaries will allow more efficient completion of discharge summaries, improve the quality of discharge summaries and improve the timeliness of delivery to the family physician. Integrating the electronic discharge summary program with the current sign-out application is a logical approach because the two processes follow each other in the flow of care, information from the sign-out application is transferable to the discharge summary and both processes are essential for maintaining the continuity of care.


Post-translational modifications regulate signalling by Ror1.
In this study, we analysed the post-translational modification of receptor tyrosine kinase-like orphan receptor (Ror1). Ror1 is highly upregulated in B cells of patients with chronic lymphocytic leukaemia (CLL). Molecularly, Ror1 acts as the Wnt receptor in the non-canonical Wnt pathway. The level of Ror1 glycosylation in HEK293 cells and in primary human CLL cells was analysed by treatment of inhibitors interfering with different steps of glycosylation process and by direct treatment of cell lysates with N-glycosidase. Ror1 ubiquitination was determined by ubiquitination assay. Functional consequences of post-translational modifications were analysed by immunohistochemistry and by analysis of cell surface proteins. Differences in Ror1 glycosylation were confirmed by analysis of 14 samples of B cells from CLL patients. We demonstrate that Ror1 is extensively modified by N-linked glycosylation. Glycosylation produces several variants of Ror1 with electrophoretic migration of approx. 100, 115 and 130 kDa. Inhibition of glycosylation interferes with cell surface localization of the 130-kDa variant of Ror1 and prevents Ror1-induced formation of filopodia. Moreover, we show that 130-kDa Ror1 is mono-ubiquitinated. Furthermore, individual CLL patients show striking differences in the electrophoretic migration of Ror1, which correspond to the level of glycosylation. Our data show that Ror1 undergoes complex post-translational modifications by glycosylation and mono-ubiquitination. These modifications regulate Ror1 localization and signalling, and are highly variable among individual CLL patients. These may suggest that Ror1 signals only in a subset of CLL patients despite Ror1 levels are ubiquitously high in all CLL patients.


Removal of exhaled particles by ventilation and deposition in a multibed airborne infection isolation room.
Removal of airborne particles in airborne infection isolation rooms is important for infection control of airborne diseases. Previous studies showed that the downward ventilation recommended by Centers for Disease Control and Prevention (CDC) could not produce the expected 'laminar' flow for pushing down respiratory gaseous contaminants and removing them via floor-level exhausts. Instead, upper-level exhausts were more efficient in removing gaseous contaminants because of upward body plumes. The conventional wisdom in the current CDC-recommended design is that floor-level exhausts may efficiently remove large droplets/particles, but such a hypothesis has not been proven. We investigated the fate of respiratory particles in a full-scale six-bed isolation room with exhausts at different locations by both experimental and computational studies. Breathing thermal manikins were used to simulate patients, and both gaseous and large particles were used to simulate the expelled fine droplet nuclei and large droplets. Gaseous and fine particles were found to be removed more efficiently by ceiling-level exhausts than by floor-level exhausts. Large particles were mainly removed by deposition rather than by ventilation. Our results show that the existing isolation room ventilation design is not effective in removing both fine and large respiratory particles. An improved ventilation design is hence recommended. Our findings of the relatively poor performance of fine-particle removal by the existing CDC design of isolation room ventilation suggests a need for improvement, and the findings of the removal of large particles by deposition, not by ventilation, suggest that floor-level exhausts are unnecessary, and that regular surface cleaning and disinfection is necessary, thus providing evidence for maintaining isolation room surface hygiene.


Bacterial Chat: Intestinal Metabolites and Signals in Host-Microbiota-Pathogen Interactions.
Intestinal bacteria employ microbial metabolites from the microbiota and chemical signaling during cell-to-cell communication to regulate several cellular functions. Pathogenic bacteria are extremely efficient in orchestrating their response to these signals through complex signaling transduction systems. Precise coordination and interpretation of these multiple chemical cues is important within the gastrointestinal (GI) tract. Enteric foodborne pathogens, such as enterohemorrhagic Escherichia coli (EHEC) and Salmonella enterica serovar Typhimurium, or the surrogate murine infection model for EHEC, Citrobacter rodentium, are all examples of microorganisms that modulate the expression of their virulence repertoire in response to signals from the microbiota or the host, such as autoinducer-3 (AI-3), epinephrine (Epi), and norepinephrine (NE). The QseBC and QseEF two-component systems, shared by these pathogens, are involved in sensing these signals. We review how these signaling systems sense and relay these signals to drive bacterial gene expression; specifically, to modulate virulence. We also review how bacteria chat via chemical signals integrated with metabolite recognition and utilization to promote successful associations among enteric pathogens, the microbiota, and the host.


Brugia malayi: stage-specific expression of carbohydrates containing N-acetyl-D-glucosamine on the sheathed surfaces of microfilariae.
Microfilariae, infective larvae, and adult worms of Brugia malayi were incubated with a panel of seven lectins in order to study the expression of surface carbohydrates. Infective larvae and adult worms did not bind any of the lectins utilized. Microfilariae, on the other hand, bound wheat germ agglutinin. The binding of this lectin was saturable and specific, and attributed to the presence of N-acetyl-D-glucosamine. In addition, microfilariae derived in vitro bound concanavalin A, indicating the presence of glucose and/or mannose on this stage of the parasite. The fact that similar concanavalin A binding was not seen on microfilariae recovered directly from the infected host implies that there is masking or loss of parasite surface antigens as microfilariae mature in vivo.


Methods of the ITC Four Country Smoking and Vaping Survey, wave 1 (2016).
To describe the methods of the 2016 International Tobacco Control (ITC) Four Country Smoking and Vaping (4CV) Survey, conducted in 2016 in Australia (AU), Canada (CA), England (EN) and the United States (US). The respondents were cigarette smokers, former smokers (quit within the previous 2 years), and at-least-weekly vapers, aged 18 years and older. Eligible cohort members from the ITC Four Country Survey (4C) were retained. New respondents were sampled by commercial firms from their panels. Where possible, ages 18-24 and vapers were oversampled. Data were collected online, and respondents were remunerated. Survey weights were calibrated to benchmarks from nationally representative surveys. Response rates by country for new recruits once invited ranged from 15.2 to 49.6%. Sample sizes for smokers/former smokers were 1504 in AU, 3006 in CA, 3773 in EN and 2239 in the US. Sample sizes for additional vapers were 727 in CA, 551 in EN and 494 in the US. The International Tobacco Control Four Country Smoking and Vaping Survey design and data collection methods allow analyses to examine prospectively the use of cigarettes and nicotine vaping products in jurisdictions with different regulatory policies. The effects on the sampling designs and response quality of recruiting the respondents from commercial panels are mitigated by the use of demographic and geographic quotas in sampling; by quality control measures; and by the construction of survey weights taking into account smoking/vaping status, sex, age, education and geography.


Transglutaminase and the pathogenesis of coeliac disease.
In 1997, a German group demonstrated that the antigen of the biomarker EMA (endomysial antibodies) in coeliac disease is a calcium-dependent thiol enzyme, transglutaminase type 2 (TG2). This most important discovery opened up an exciting field of research aimed at a better understanding of the pathogenesis of coeliac disease, a T-cell-driven autoimmune disorder with a prevalence of about 1%. The accidental activation of TG2, possibly caused by a stress-induced local deficiency of zinc in the intestinal wall, might play a key role where the enzyme catalyzes an atypical deamidation of specific glutamine residues of food gliadins. The genetic contribution is HLA DQ2 or DQ8, which can form a complex with the TG2-modified gliadin residues, resulting in an immune response with the formation of antibodies against both gliadin and the enzyme. Indeed, the immunopathogenesis of coeliac disease can now be recognized partly at the molecular level. Progress has already improved the opportunities for laboratory diagnostics and, hopefully, new ways of treating and preventing coeliac disease will become available. These exciting developments might stimulate research within other fields of autoimmune disorders. With its focus on TG2, this review highlights some of the intriguing mechanisms of the pathogenesis of coeliac disease, such as the structure of the neo-antigen, the involvement of calcium and zinc, and the effects of coeliac antibodies on TG2 activity. Moreover, the many pitfalls due to dubious laboratory practice are addressed, as is the potential when a fundamental biological mechanism is understood at the molecular level.


Lower rim 1,3-diderivative of calix[4]arene-appended salicylidene imine (H(2)L): experimental and computational studies of the selective recognition of H(2)L toward Zn(2+) and sensing phosphate and amino acid by [ZnL].
A new 1,3-diderivative of calix[4]arene appended with hydroxymethyl salicylyl imine has been synthesized and its ion recognition toward biologically relevant M(n+) ions studied. The receptor H(2)L showed selectivity toward Zn(2+) by switch-on fluorescence among the 12 metal ions studied with a detection limit of 192 ppb. The interaction of Zn(2+) with H(2)L has been further supported by absorption studies, and the stoichiometry of the complex formed (1:1) has been established on the basis of absorption and ESI MS. Competitive ion titrations carried out reveal that the Zn(2+) can be detected even in the presence of other metal ions of bioimportance. The mode of interaction of Zn(2+) with conjugate has been established by a fleet of computational calculations carried out in a cascade manner, either on the ligand or on the complex, wherein the final optimizations were carried out by the density functional theory (DFT) and found that the Zn(2+) and Cd(2+) indeed bind differently. In situ prepared [ZnL] complex responds to both inorganic phosphate as well as AMP, ADP, and ATP with a minimum detection limit of 426 ppb wherein the Zn(2+) from the complex is detached and recomplexed by the added phosphate moiety. It has been possible to build an INHIBIT logic gate for the conjugate using Zn(2+) and HPO(4)(2-) as inputs by monitoring the fluorescence emission band at 444 nm as output. The amino acid sensing abilities of [ZnL] have been explored by fluorescence and absorbance spectroscopy where it showed selectivity toward Cys, Asp, and His through the formation of the Zn(2+) complex of these amino acids by chelating through their side chain moieties. Thus, while H(2)L is selective for Zn(2+) among a number of cations, the [ZnL] is selective toward phosphate among a number of anions and also toward Asp, Cys, and His among the naturally occurring amino acids.


Toxic effects produced or mediated by human eosinophil granule components on Trypanosoma cruzi.
The eosinophil granule major basic protein, the eosinophil cationic protein, and the eosinophil-derived neurotoxin were found to be lytic for Trypanosoma cruzi trypomastigotes from blood, cell cultures, or insect vectors and for cultured amastigotes. The toxic effects of the major basic and cationic proteins were inhibited by the polyanions heparin and dextran sulfate, in keeping with the cationic nature of these proteins, or by heat denaturation, suggesting that molecular conformation was also relevant. The lytic activity of the neurotoxin was not inhibited by heating at 56 degrees C for 4 hr, establishing an additional difference with the eosinophil cationic protein. Heparin had only a slight inhibitory effect on the toxicity of the neurotoxin, and dextran sulfate was inactive even at 25 mg/ml. Although both the eosinophil cationic protein and the neurotoxin possess ribonuclease activity, only the toxicity of the latter was abolished by the ribonuclease inhibitor RNasin (Promega, Madison, Wisconsin) or by a competitive substrate, yeast ribonucleic acid. Eosinophil peroxidase significantly increased the extent of trypomastigote or amastigote killing by hydrogen peroxide in the presence of iodide. This effect was abrogated by sodium azide, bovine serum albumin, or gelatin, known inhibitors of the eosinophil peroxidase + halide + hydrogen peroxide system. These results suggest that the destruction of T. cruzi trypomastigotes and amastigotes by eosinophils may result from toxic mechanisms involving several granule proteins.


Biological Behavior and Long-Term Outcomes of Carcinoma In Situ in Upper Urinary Tract Managed by Radical Nephroureterectomy.
In patients with urothelial carcinoma CIS (carcinoma in situ) generally has a poor prognosis. However, to our knowledge the outcomes of pure/primary CIS and the behavior of CIS concomitant with pTa-pT4 upper tract urothelial carcinoma managed by nephroureterectomy have not been previously specified. We explored the biological and prognostic features of concomitant CIS compared with those of pure/primary CIS. We queried a multicenter upper tract urothelial carcinoma database. Data from NUOG (Nishinihon Uro-Oncology Group) were analyzed, including patient gender, age, presence of bladder cancer and pT stage. Clinicopathological features were compared between the different subtypes. Cancer specific and overall survival, and the relative excess risk of death were estimated by CIS subtype. We identified 163 patients with CIS in the upper urinary tract, of whom pure/primary CIS was noted in 24.5%. In the concomitant CIS cohort the pathological diagnosis of the nonCIS region was pTa, pT1, pT2, pT3 and pT4 in 4.9%, 22.8%, 25.2%, 44.7% and 1.6% of patients, respectively. The sensitivity of a selective urine cytology test was higher in the pure/primary CIS group than in the concomitant CIS group (60.0% vs 37.4%). At a median followup of 32 months 10-year estimated mean cancer specific survival was 92.4 months (range 83.7 to 101.0) in the overall CIS cohort. Ten-year estimated mean cancer specific survival in patients with pure/primary CIS was significantly longer than in patients with concomitant carcinoma in situ (111.8 months, range 101.0 to 122.6 vs 85.89, range 75.3 to 96.5, log rank p = 0.007). Patients presenting with concomitant CIS have a worse outcome than those who present with pure/primary CIS, suggesting a need to differentiate these 2 entities in the treatment decision process.


Effect of inhibition of ornithine decarboxylase activity in a model of acute hepatocellular necrosis.
The effect of blockade of the enzyme ornithine decarboxylase by difluoromethylornithine (DFMO) on hepatocellular necrosis and survival in rats treated with thioacetamide (TAA) was investigated. In one experiment, the effect of DFMO on survival of rats with TAA-induced acute hepatocellular necrosis was determined. In another experiment, blood and liver specimens were obtained from DFMO or saline-treated rats 24 h after the administration of TAA for determinations of serum alanine aminotransferase (ALT) and liver content of polyamines and microsomal cytochrome P-450 and for assessment of hepatic histology. Liver polyamines were determined by reversed-phase HPLC and microsomal cytochrome P-450 content by dithionite-difference spectroscopy of CO-treated homogenates. The severity of hepatocellular necrosis was scored blindly. TAA-treated rats that received DFMO survived longer than saline-treated controls (P < 0.01). Serum ALT and liver putrescine concentrations were lower and the histological severity of acute hepatocellular necrosis was less in DFMO-treated rats with TAA-induced hepatocellular necrosis than in saline-treated controls (P < 0.05, P < 0.01 and P < 0.05, respectively). Total cytochrome P-450 levels were similar in DFMO and saline-treated rats with TAA-induced hepatocellular necrosis. DFMO increases survival in TAA-induced fulminant hepatic failure by decreasing the severity of acute hepatocellular necrosis. The beneficial effects of DFMO do not appear to be mediated by its effects on polyamine metabolism, but may be attributable to an effect of DFMO on thioacetamide metabolism or on an alternative pathway of ornithine metabolism.


[Monomorphic ventricular tachycardia during the ajmaline test].
A 44-year-old male patient admitted with palpitations was diagnosed with tachycardia with wide QRS, but recovered after being treated with amiodarone. The patient's coronary angiography was normal. As the patient's resting ECG was compatible with Brugada type 2, an ajmaline challenge test was scheduled. The infusion procedure was suspended following an observation of type 1 ECG findings in the 4th minute of infusion. Approximately 10-15 seconds later, a monomorphic ventricular tachycardia with a rate of 150 beats/minute developed. In the follow-up, the patient's heartbeat returned spontaneously to the sinus rhythm within 3-4 minutes. Polymorphic ventricular tachycardia or ventricular fibrillation tachyarrhythmias usually result in syncope or sudden cardiac death in cases of Brugada syndrome, while monomorphic tachycardia, as in our case, is rare. Here, we present a rare case of monomorphic ventricular tachycardia, which was observed during the ajmaline challenge test.


The role of telomeres in Etoposide induced tumor cell death.
Etoposide, a topoisomerase II poison is used in the treatment of a number of solid tumors. Contradictory data exist on the role of the telomere/telomerase complex in etoposide induced apoptosis. Therefore we examined the effects of etoposide treatment in the neuroblastoma cell line SHSY5Y, with very short telomeres and the acute lymphoblastic T cell line 1301, which displays extremely long telomeres. Both short-term and continuous exposure to the drug were examined. Etoposide induced widespread DNA damage followed by DNA damage foci formation and ultimately growth arrest and apoptosis in a concentration-dependent manner. However, length of telomeres and of single stranded telomeric G rich overhangs did not change significantly under the treatments in any cell line. There was no significant induction of single-strand breaks in the G-rich strand of telomeres. Telomerase activity was transiently upregulated under low concentrations of etoposide, while high concentrations resulted in decreased telomerase activity only after onset of apoptosis. Telomerase overexpression protected against etoposide induced apoptosis in fibroblasts. The data suggest that telomeres are not major signal transducers towards growth arrest or apoptosis after etoposide treatment. However, upregulation of telomerase might be part of an attempted adaptative response, which protects cells by a mechanism that might be independent of telomere length maintenance.


Dose response of endotoxin on hepatocyte and muscle mitochondrial respiration in vitro.
Results on mitochondrial dysfunction in sepsis are controversial. We aimed to assess effects of LPS at wide dose and time ranges on hepatocytes and isolated skeletal muscle mitochondria. Human hepatocellular carcinoma cells (HepG2) were exposed to placebo or LPS (0.1, 1, and 10 μg/mL) for 4, 8, 16, and 24 hours and primary human hepatocytes to 1 μg/mL LPS or placebo (4, 8, and 16 hours). Mitochondria from porcine skeletal muscle samples were exposed to increasing doses of LPS (0.1-100 μg/mg) for 2 and 4 hours. Respiration rates of intact and permeabilized cells and isolated mitochondria were measured by high-resolution respirometry. In HepG2 cells, LPS reduced mitochondrial membrane potential and cellular ATP content but did not modify basal respiration. Stimulated complex II respiration was reduced time-dependently using 1 μg/mL LPS. In primary human hepatocytes, stimulated mitochondrial complex II respiration was reduced time-dependently using 1 μg/mL LPS. In isolated porcine skeletal muscle mitochondria, stimulated respiration decreased at high doses (50 and 100 μg/mL LPS). LPS reduced cellular ATP content of HepG2 cells, most likely as a result of the induced decrease in membrane potential. LPS decreased cellular and isolated mitochondrial respiration in a time-dependent, dose-dependent and complex-dependent manner.


Effects of chronic administration of mestranol on alpha and beta adrenergic responsiveness in female rats.
Several alpha and beta adrenergic responses were studied in female rats after treatment with a low dose of the synthetic estrogen, mestranol (15 micrograms i.p. biweekly), for 4 to 6 weeks and compared with untreated controls. The response of blood pressure to exogenously administered norepinephrine was measured in conscious rats by means of an indwelling catheter in the femoral artery. Basal systolic blood pressure was not different between control and treated groups, or was any difference observed in peak systolic pressure after acute i.v. administration of l-norepinephrine in concentrations of 0.0625, 0.125, 0.250 and 0.625 micrograms. In contrast, the half-time of the blood pressure response was significantly prolonged after administration of the various concentrations of norepinephrine to mestranol-treated rats. The half-time of the pressor response observed in control animals administered 0.625 micrograms of norepinephrine was elicited in mestranol-treated animals by only 0.250 micrograms of norepinephrine. Analysis of the time course of the pressor response indicates that mestranol treatment altered the duration of the blood pressure increase without an apparent change in the onset of the pressor response. No differences between groups were observed in beta adrenergic responsiveness measured in terms of the isoproterenol-induced increase in either heart rate (beta-1 response) or water intake (beta-2 response). Finally, the contractile response of aortic rings from mestranol-treated rats to both l-norepinephrine (10(-9) to 10(-5) M) and l-phenylephrine (10(-8) to 10(-4) M) was significantly less than that of aortic rings from control rats. These data indicate, therefore, that in vivo cardiovascular responsiveness to norepinephrine does not reflect the attenuated vascular reactivity of isolated aortic rings. Insofar as the dominant feature of the in vivo adrenergic response appears to be prolongation of pressor action, the present study suggests that processes involved in the inactivation of circulating norepinephrine may be altered by chronic treatment with a low-dose of mestranol.


Investigation of the association between oxygen reserve index and arterial partial oxygen pressure in anesthetized dogs.
To evaluate the relationship between oxygen reserve index (ORI) and arterial partial pressure of oxygen (PaO2) in anesthetized dogs. Prospective experimental study. A total of eight healthy adult Beagle dogs with a median age of 38 (range 20-87) months and a median body mass of 8.6 (range 7.0-13.8) kg. After induction of general anesthesia with propofol, dogs were mechanically ventilated and anesthesia maintained with isoflurane carried in oxygen. Arterial blood samples were collected from a catheter placed in the femoral artery. ORI was measured by placing a CO-oximeter sensor on the tongue. Inspired oxygen fraction (FiO2) was increased from 21% to > 95% in increments of 5%. PaO2 and ORI were recorded and compared at different times. The relationship between ORI and PaO2 was investigated using a nonlinear function, the Hill equation, and a linear regression analysis was performed, as appropriate. A total of 128 pairs of values were compared for all dogs. Applying the Hill equation to the relationship between ORI and PaO2 resulted in R2 = 0.80 (p < 0.001) with a Hill coefficient of 3.7. It was predicted that ORI ranged 0.1-0.9 as PaO2 ranged 127.0-417.9 mmHg and that in the more linear portion of the range, PaO2 of 127.0-289.9 mmHg ORI ranged 0.1-0.7. Linear regression analysis in the more linear portion showed a weak correlation (R2 = 0.29, p = 0.006). In the present study, the Hill equation predicted the relationship between PaO2 and ORI for PaO2 ranging 127.0-417.9 mmHg in anesthetized dogs. However, in the linear portion of the PaO2, the coefficient of determination was low, indicating that ORI is not a surrogate for PaO2.


Estradiol synthesis and release in cultured female rat bone marrow stem cells.
Bone marrow stem cells (BMSCs) have the capacity to differentiate into mature cell types of multiple tissues. Thus, they represent an alternative source for organ-specific cell replacement therapy in degenerative diseases. In this study, we demonstrated that female rat BMSCs could differentiate into steroidogenic cells with the capacity for de novo synthesis of Estradiol-17 β (E2) under high glucose culture conditions with or without retinoic acid (RA). The cultured BMSCs could express the mRNA and protein for P450arom, the enzyme responsible for estrogen biosynthesis. Moreover, radioimmunoassay revealed that BMSCs cultured in the present culture system produced and secreted significant amounts of testosterone, androstenedione, and E2. In addition, RA promoted E2 secretion but did not affect the levels of androgen. These results indicate that BMSCs can synthesize and release E2 and may contribute to autologous transplantation therapy for estrogen deficiency.


Evolutionary active transposable elements in the genome of the coelacanth.
The apparent morphological stasis in the lineage of the coelacanth, which has been called a "living fossil" by many, has been suggested to be causally related to a slow evolution of its genome, with strongly reduced activity of transposable elements (TEs). Analysis of the African coelacanth showed that at least 25% of its genome is constituted of transposable elements including retrotransposons, endogenous retroviruses and DNA transposons, with a strong predominance of non-Long Terminal Repeat (non-LTR) retrotransposons. The coelacanth genome has been shaped by four major general bursts of transposition during evolution, with major contributions of LINE1, LINE2, CR1, and Deu non-LTR retrotransposons. Many transposable elements are expressed in different tissues and might be active. The number of TE families in coelacanth, but also in lungfish, is lower than in teleost fish, but is higher than in chicken and human. This observation is in agreement with the hypothesis of a sequential elimination of many TE families in the sarcopterygian lineage during evolution. Taken together, our analysis indicates that the coelacanth contains more TE families than birds and mammals, and that these elements have been active during the evolution of the coelacanth lineage. Hence, at the level of transposable element activity, the coelacanth genome does not appear to evolve particularly slowly.


The association of statin therapy with clinicopathologic outcomes and survival among patients with localized renal cell carcinoma undergoing nephrectomy.
Although statins have been found to induce apoptosis and demonstrate antimetastases activity both in vitro and in vivo for renal cell carcinoma (RCC), clinical evidence of a role for these medications is limited. We evaluated the association of statin therapy with outcomes among patients with surgically treated localized RCC. We reviewed 2,357 patients who underwent nephrectomy between 1995 and 2009 for pNx/0, M0 RCC. Of these, 630 (27%) were taking statins within 3 months of surgery. Progression-free survival, cancer-specific survival, and overall survival were estimated using the Kaplan-Meier method. The associations of statin use with clinicopathologic outcomes were evaluated with multivariable logistic and proportional hazards regression models. Statin therapy at the time of nephrectomy was not significantly associated with the risks of locally advanced (pT3-4) pathologic tumor stage (odds ratio = 0.96; P = 0.80) or high (3-4) tumor grade (odds ratio = 1.11; P = 0.30). Median postoperative follow-up was 7.8 years. Compared with patients not on statin therapy, patients taking statins at surgery had similar 10-year progression-free survival (80% vs. 79%; P = 0.56), cancer-specific survival (85% vs. 84%; P = 0.71), and overall survival (59% vs. 64%; P = 0.11). On multivariable analysis, statin use was not significantly associated with the risks of disease progression (hazard ratio [HR] = 1.22; P = 0.10), death from RCC (HR = 1.02; P = 0.90), or all-cause mortality (HR = 0.84; P = 0.05). We found no independent association between preoperative statin therapy and oncologic outcomes among patients with surgically treated localized RCC. Our data thus do not support an anticancer role for statin therapy in this setting.


Model order reduction for bifurcating phenomena in fluid-structure interaction problems.
This work explores the development and the analysis of an efficient reduced order model for the study of a bifurcating phenomenon, known as the Coandă effect, in a multi-physics setting involving fluid and solid media. Taking into consideration a fluid-structure interaction problem, we aim at generalizing previous works towards a more reliable description of the physics involved. In particular, we provide several insights on how the introduction of an elastic structure influences the bifurcating behavior. We have addressed the computational burden by developing a reduced order branch-wise algorithm based on a monolithic proper orthogonal decomposition. We compared different constitutive relations for the solid, and we observed that a nonlinear hyper-elastic law delays the bifurcation w.r.t. the standard model, while the same effect is even magnified when considering linear elastic solid.


Onset and exacerbation of obsessive-compulsive disorder in pregnancy and the postpartum period.
The primary goal of this study was to examine the impact of pregnancy, childbirth, and menstruation on the onset of obsessive-compulsive disorder (OCD) and/or exacerbation of OCD symptoms. One hundred twenty-six women aged between 18 and 69 years attending a university-based OCD clinic who met DSM-IV criteria for OCD according to the Structured Clinical Interview for DSM-IV Disorders were interviewed retrospectively to assess OCD onset and symptom exacerbation in relationship to reproductive events. Women were placed into 2 groups: those who had ever been pregnant (ever pregnant group) and those who had never been pregnant. The ever pregnant group was further subdivided into those who reported onset of OCD in the perinatal period (perinatal-related group) and those who denied onset related to pregnancy (nonperinatal-related group). Between-group comparisons were done using a Student t test for continuous measures, and categorical variables were assessed using the χ² test. Of the 78 women in the ever pregnant group, 32.1% (n = 24) had OCD onset in the perinatal period (perinatal-related group), 15.4% in pregnancy, 14.1% at postpartum, and 1.3% after miscarriage. Of 132 total pregnancies, 34.1% involved an exacerbation of symptoms, 22.0% involved an improvement in OCD symptoms, and 43.9% did not change symptom severity in women with preexisting illness. Women in the perinatal-related group and women with perinatal worsening of preexisting OCD were more likely to have premenstrual worsening of OCD symptoms compared to women in the nonperinatal-related group (66% vs 39%, P = .047). Findings from this study provide additional evidence that pregnancy and childbirth are frequently associated with the onset of OCD or worsening of symptoms in those with preexisting disorder. In addition, there appears to be continuity between OCD onset and/or exacerbation across the reproductive life cycle, at least with menstruation and pregnancy.


UNWIRED E-MED: the next generation of wireless and internet telemedicine systems.
The movement of telemedicine to wireless and mobile Internet applications is imminent in the next few years. This migration from desktop platforms to wireless and mobile configurations will have a significant impact on future healthcare delivery systems and their globalization. Recent telecommunications and biomedical computing advances will significantly enhance the current methodologies of telemedicine and telecare systems. This editorial will present some of the evolutionary issues and important aspects that have to be considered in developing technologies for the next generation of Internet and third generation of mobile systems geared for future telemedical applications. These will provide new dimensions to existing medical services and areas of outreach that are not possible with the current generation that will have tremendous impact on how healthcare delivery will be shaped for the 21st century.


Expression of invasion-related extracellular matrix molecules in human glioblastoma versus intracerebral lung adenocarcinoma metastasis.
Tumor cell invasion into the surrounding brain tissue is mainly responsible for the failure of radical surgical resection, with tumor recurrence in the form of microdisseminated disease. Extracellular matrix (ECM)-related molecules and their receptors predominantly participate in the invasion process, including cell adhesion to the surrounding microenvironment and cell migration. The extent of infiltration of the healthy brain by malignant tumors strongly depends on the tumor cell type. Malignant gliomas show much more intensive peritumoral invasion than do metastatic tumors. In this study, the mRNA expression of 30 invasion-related molecules (twenty-one ECM components, two related receptors, and seven ECM-related enzymes) was investigated by quantitative reverse transcriptase-polymerase chain reaction. Fresh frozen human tissue samples from glioblastoma (GBM), intracerebral lung adenocarcinoma metastasis, and normal brain were evaluated. Significant differences were established for 24 of the 30 molecules. To confirm our results at the protein level, immunohistochemical analysis of seven molecules was performed (agrin, neurocan, syndecan, versican, matrix metalloproteinase 2 [MMP-2], MMP-9, and hyaluronan). Determining the differences in the levels of invasion-related molecules for tumors of different origins can help to identify the exact molecular mechanisms that facilitate peritumoral infiltration by glioblastoma cells. These results should allow the selection of target molecules for potential chemotherapeutic agents directed against highly invasive malignant gliomas.


Physico-chemical properties, probiotic survivability, microstructure, and acceptability of a yogurt-like symbiotic oats-based product using pre-polymerized whey protein as a gelation agent.
Consumption of a food product containing prebiotics and probiotics has been recognized as an important factor in lowering risk of intestinal cancer and gastrointestinal diseases and risks associated with high cholesterol. An oats-based symbiotic yogurt-like food (Oagurt) was developed using oats and probiotics (Lactobacillus acidophilus, Lactobacillus casei, and Bifidobacterium), with pre-polymerized whey protein (PWP) as a gelation agent. The product was also fortified with inulin to increase soluble fiber, minerals, and vitamins. Physico-chemical analyses and 9 wk shelf life for viability of probiotics and changes in pH and viscosity were carried out for formulations with (F) and without (C) fortification. Results of the shelf life study showed that both L. casei and Bifidobacterium remained at therapeutic levels: 4.8 x 10(6) CFU/g (F), 4.3 x 10(6) CFU/g (C) and 3.1 x 10(6) CFU/g (F), 3.17 x 10(6) CFU/g (C) after 9 wk. However L. acidophilus did not survive after 3 wk. Viscosity and pH decreased significantly during the study with the difference between formulations also significant for pH (P < 0.0001). Scanning electron microscopy of samples revealed that the pre-polymerized whey protein played a major role in the structure of the gel with an increased protein network structure visible at higher PWP levels. A consumer acceptability study showed that the product was "fair" for all organoleptic attributes.


Speech recognition in natural background noise.
In the real world, human speech recognition nearly always involves listening in background noise. The impact of such noise on speech signals and on intelligibility performance increases with the separation of the listener from the speaker. The present behavioral experiment provides an overview of the effects of such acoustic disturbances on speech perception in conditions approaching ecologically valid contexts. We analysed the intelligibility loss in spoken word lists with increasing listener-to-speaker distance in a typical low-level natural background noise. The noise was combined with the simple spherical amplitude attenuation due to distance, basically changing the signal-to-noise ratio (SNR). Therefore, our study draws attention to some of the most basic environmental constraints that have pervaded spoken communication throughout human history. We evaluated the ability of native French participants to recognize French monosyllabic words (spoken at 65.3 dB(A), reference at 1 meter) at distances between 11 to 33 meters, which corresponded to the SNRs most revealing of the progressive effect of the selected natural noise (-8.8 dB to -18.4 dB). Our results showed that in such conditions, identity of vowels is mostly preserved, with the striking peculiarity of the absence of confusion in vowels. The results also confirmed the functional role of consonants during lexical identification. The extensive analysis of recognition scores, confusion patterns and associated acoustic cues revealed that sonorant, sibilant and burst properties were the most important parameters influencing phoneme recognition. . Altogether these analyses allowed us to extract a resistance scale from consonant recognition scores. We also identified specific perceptual consonant confusion groups depending of the place in the words (onset vs. coda). Finally our data suggested that listeners may access some acoustic cues of the CV transition, opening interesting perspectives for future studies.


Smaller visual angles show greater benefit of letter boldness than larger visual angles.
Research has shown that fonts viewed at a smaller visual angle benefit from greater letter boldness. Since small and large visual angles operate on different spatial frequencies, we examined whether the effect was dependent on font size. By applying a paradigm of single-letter exposure across two experiments, we showed that fonts of thinner letter strokes and of extreme boldness decreased recognition for all tested font sizes, and that there was a positive effect of boldness at small visual angles which did not occur at large visual angles. The paper provides evidence that bolder fonts are less effective at improving recognition at larger visual angles, and that over a scale of font weights there is a drop-off at the lightest and the heaviest extremes at all tested font sizes.


Pathophysiologic mechanisms linking impaired cardiovascular health and neurologic dysfunction: the year in review.
The nervous system and cardiovascular system have long been known to interact. Only more recently, however, have the mechanisms driving this interaction become more clearly understood. Although many psychological disturbances, including depression and anxiety, are known to predict poor outcomes in patients with cardiovascular disease, other neurologic disturbances, such as migraine and stroke, have been connected to poor cardiovascular outcomes as well. Although these connections were traditionally thought to be due to shared risk factors, recent research has focused on pathophysiologic mechanisms underlying these interactions, including neuroendocrine dysregulation, genetic predisposition, and vascular dysfunction.


The First 250 ms of Auditory Processing: No Evidence of Early Processing Negativity in the Go/NoGo Task.
Past evidence of an early Processing Negativity in auditory Go/NoGo event-related potential (ERP) data suggests that young adults proactively process sensory information in two-choice tasks. This study aimed to clarify the occurrence of Go/NoGo Processing Negativity and investigate the ERP component series related to the first 250 ms of auditory processing in two Go/NoGo tasks differing in target probability. ERP data related to each task were acquired from 60 healthy young adults (M = 20.4, SD = 3.1 years). Temporal principal components analyses were used to decompose ERP data in each task. Statistical analyses compared component amplitudes between stimulus type (Go vs. NoGo) and probability (High vs. Low). Neuronal source localisation was also conducted for each component. Processing Negativity was not evident; however, P1, N1a, N1b, and N1c were identified in each task, with Go P2 and NoGo N2b. The absence of Processing Negativity in this study indicated that young adults do not proactively process targets to complete the Go/NoGo task and/or questioned Processing Negativity's conceptualisation. Additional analyses revealed stimulus-specific processing as early as P1, and outlined a complex network of active neuronal sources underlying each component, providing useful insight into Go and NoGo information processing in young adults.


Nutrition and gastrointestinal tract assessment and management of children with dysphagia.
Limited ability to take in nutrients places young patients with dysphagia at risk for malnutrition and failure to gain weight. These children require careful evaluation and ongoing monitoring of growth and nutritional status. Gastroesophageal reflux and recurrent vomiting may contribute to dysphagia when the refluxate causes laryngopharyngeal irritation and can increase the morbidity in patients prone to aspiration. A paucity of evidence-based literature on relevant topics demands both clinical judgment and an interdisciplinary approach for management decisions for these issues. Advances in nutrition and management of aerodigestive conditions related to dysphagia will be reviewed.


Biased information search in group decision making.
Research has shown that people prefer supporting to conflicting information when making decisions. Whether this biased information search also occurs in group decision making was examined in three experiments. Experiment 1 indicated that groups as well as individuals prefer supporting information and that the strength of this bias depends on the distribution of the group members' initial decision preferences. The more group members had chosen the same alternative prior to the group discussion (group homogeneity), the more strongly the group preferred information supporting that alternative. Experiment 2 replicated these results with managers. Experiment 3 showed that the differences between homogeneous and heterogeneous groups reflect group-level processes. Higher commitment and confidence in homogeneous groups mediated this effect. Functional and dysfunctional aspects of biased information seeking in group decision making are discussed.


The effects of microenvironment on the redifferentiation of regenerating neurones: neurite architecture, acetylcholine receptors and Ca2+ channel distribution.
Severed adult neurones, which are capable of regrowth, encounter different microenvironments from those encountered during development. Moreover, adult neurones may respond in a different manner from developing neurones to the same environmental cues. Thus, the recovery of the integrative and transmission capabilities (which depend on the neuronal architecture, passive and active membrane properties, and synaptic receptor distribution) by a regenerating adult neurone may not be complete. In the present review, we examine several aspects of the outcome of the interaction between the microenvironment and regrowing neurones using the cockroach giant interneurones (GINs) as a model system. We demonstrate that whereas extrinsic cues govern the morphological redifferentiation and distribution of synaptic receptors, the distribution of voltage-dependent Ca2+ channels is to a large extent determined by intrinsic factors. The pathway of regrowth and the architecture of regenerating GINs were studied by examination of intracellularly stained fibres. The environments provided by the connectives and ganglia are different. The elongating sprouts in the connective appeared as smooth cylinders. Within the ganglionic domain, the main longitudinal sprouts emitted neurites which extended and branched into the neuropile. The local cues for branching of neurites were eliminated by freezing and thawing of the ganglia prior to the arrival of the growing tips. The failure to extend neurites under these conditions is attributed to the elimination of extrinsic signals for morphological redifferentiation of the fibres, since the same fibres emit neurites in anterior ganglia which have not been subjected to freezing and thawing. The distribution of acetylcholine receptors (AChRs) on the GINs was mapped by ionophoretic application of ACh. In both the intact and regenerating GINs receptors were located only on the neurites. Freezing and thawing of a ganglion eliminated the local signals for insertion and/or activation of AChRs on the neurites. Thus, both the morphological redifferentiation and the distribution of AChRs are affected by the microenvironment. Voltage-dependent Ca2+ channels were detected after intracellular injection of tetraethylammonium into the GIN and in the presence of tetrodotoxin (TTX) and Ba2+ in the extracellular space. The regrowing axon tips always revealed large barium action potentials independent of the CNS microenvironment. This observation is consistent with the hypothesis that Ca2+ plays an important role in the growth process. However, increased Ba2+ responsiveness was also observed in axonal segments proximal to the region of neuronal extension.(ABSTRACT TRUNCATED AT 400 WORDS)


Pleiotropic roles of Clostridium difficile sin locus.
Clostridium difficile is the primary cause of nosocomial diarrhea and pseudomembranous colitis. It produces dormant spores, which serve as an infectious vehicle responsible for transmission of the disease and persistence of the organism in the environment. In Bacillus subtilis, the sin locus coding SinR (113 aa) and SinI (57 aa) is responsible for sporulation inhibition. In B. subtilis, SinR mainly acts as a repressor of its target genes to control sporulation, biofilm formation, and autolysis. SinI is an inhibitor of SinR, so their interaction determines whether SinR can inhibit its target gene expression. The C. difficile genome carries two sinR homologs in the operon that we named sinR and sinR', coding for SinR (112 aa) and SinR' (105 aa), respectively. In this study, we constructed and characterized sin locus mutants in two different C. difficile strains R20291 and JIR8094, to decipher the locus's role in C. difficile physiology. Transcriptome analysis of the sinRR' mutants revealed their pleiotropic roles in controlling several pathways including sporulation, toxin production, and motility in C. difficile. Through various genetic and biochemical experiments, we have shown that SinR can regulate transcription of key regulators in these pathways, which includes sigD, spo0A, and codY. We have found that SinR' acts as an antagonist to SinR by blocking its repressor activity. Using a hamster model, we have also demonstrated that the sin locus is needed for successful C. difficile infection. This study reveals the sin locus as a central link that connects the gene regulatory networks of sporulation, toxin production, and motility; three key pathways that are important for C. difficile pathogenesis.


Efficient genetic reprogramming of unmodified somatic neural progenitors uncovers the essential requirement of Oct4 and Klf4.
Significant breakthroughs have been recently achieved in reprogramming somatic cells to a pluripotent embryonic state by the ectopic expression of specific transcription factors. One of the major drawbacks of reprogramming strategies lays in the low efficiency of the process. It is likely that the required complex epigenetic-remodeling events could be cell-type specific and more rational approaches to cell source selection might help to improve the outcome of the procedure. Because the use of somatic stem cells, and specifically neural stem cells (NSCs), as nuclear donors significantly increased the efficiency of somatic cell nuclear transfer, we aimed to determine whether genetically unmodified somatic NSCs could be more easily reprogrammed to pluripotency than unmodified mouse embryonic fibroblasts. Retroviral transduction of the factors Oct4, Sox2, Klf4, and c-Myc successfully reverted NSCs to a pluripotent embryonic stem cell-like state with a 2-fold efficiency increase, faster kinetic, and with a lower number of viral integrations. Quantification analysis of reprogramming-associated genes revealed that NSCs endogenously expressed high levels of Sox2 and c-Myc. Accordingly, NSCs could be successfully induced to pluripotency through the ectopic viral expression of the other two factors (Oct4 and Klf4). These findings suggest that endogenous expression of reprogramming genes could help the reprogramming process and somatic stem cells might be more prone to reprogramming due to their specific genetic background. Genetic-based somatic cell screening might provide essential information for the selection of alternative cell sources more suitable to direct reprogramming.


Media use and psychosocial adjustment in children and adolescents.
Currently, television and new forms of media are readily available to children and adolescents in their daily lives. Excessive use of media can lead to negative physical and psychosocial health effects. This study aimed to describe children's media use, including media multitasking, as well as the associations between media use and their psychosocial adjustment. This study recruited 339 participants aged 10-15 years from an international school. The children and their care givers were asked to complete the Strengths and Difficulties Questionnaire independently to evaluate the psychosocial problems of the children. The mean age of the study participants was 12.4 ± 1.5 years, who were recruited from grades 5 to 9. Multitasking media use was reported in 59.3% of participants. The average total media exposure time was 7.0 h/day. The behavioural problem scores from self-reports were greater with increased media use time. After adjusting for confounding variables, the school report and sleep problems were among the factors associated with the total behavioural problem scores from the multiple linear regression analysis (P = 0.001 and <0.001, respectively), whereas age and average total media exposure time were significantly associated with the prosocial behaviour scores reported by the children (P = 0.004 and 0.02, respectively). Multitasking media use was not significantly associated with the total difficulties scores or the prosocial behaviour scores in this study. Increased media use time was significantly associated with decreased prosocial behaviour scores in children in this study. This can provide important information to parents regarding media use in children.


Rhizobium etli bv. mimosae, a novel biovar isolated from Mimosa affinis.
Fifty rhizobial isolates from root nodules of Mimosa affinis, a small leguminous plant native to Mexico, were identified as Rhizobium etli on the basis of the results of PCR-RFLP and RFLP analyses of small-subunit rRNA genes, multilocus enzyme electrophoresis and DNA-DNA homology. They are, however, a restricted group of lineages with low genetic diversity within the species. The isolates from M. affinis differed-from the R. etli strains that orginated from bean plants (Phaseolus vulgaris) in the size and replicator region of the symbiotic plasmid and in symbiotic-plasmid-borne traits such as nifH gene sequence and organization, melanin production and host specificity. A new biovar, bv. mimosae, is proposed within R. etli to encompass Rhizobium isolates obtained from M. affinis. The strains from common bean plants have been designated previously as R. etli bv. phaseoli. Strains of both R. etli biovars could nodulate P. vulgaris, but only those of bv. mimosae could form nitrogen-fixing nodules on Leucaena leucocephala.


MR - eyes for cancer: looking within an impenetrable disease.
Probe development is a critical component in cancer imaging, and novel probes are making major inroads in several aspects of cancer detection and image-guided treatments. Intrinsic MR probes such as signals from metabolites and their chemical shifts have been used for more than a decade to understand cancer physiology and metabolism. Through the integration of technology, molecular biology, and chemistry, the last few years have witnessed an explosion of extrinsic probes for molecular and functional imaging of cancer that, together with techniques such as CEST and hyperpolarization, have significantly expanded the repertoire of MR techniques in basic and translational investigations of many different aspects of cancer. Furthermore, incorporation of MR probes into multifunctional nanoparticles and multimodality imaging platforms have opened new opportunities for MR in image-guided diagnosis and therapy of cancer. Here we have provided an overview of recent innovations that have occurred in the development of MRI probes for molecular and functional imaging of cancer. Although most of these novel probes are not clinically available, they offer significant promise for future translational applications. In this review, we have highlighted the areas of future development that are likely to have a profound impact on cancer detection and treatment.


Contraceptive behavior among sexually active Hispanic adolescents.
The purpose of this study was to examine those factors associated with the contraceptive behavior of a national representative sample of Hispanic female adolescents. The subjects included all (n = 85) unmarried, sexually active Hispanic women, aged 15 to 19, from the 1982 National Survey of Family Growth. Contraceptive behavior was measured on a normalized scale, ranging from oral contraceptives to no contraception. Mexican/American and Central/South American background females were more likely (p less than 0.031) to use effective birth control than Puerto Rican, Cuban, and other Hispanic background subjects. Twenty additional social, behavioral, and demographic variables were found to be significantly associated (p less than 0.05) with contraceptive behavior. Based on multiple regression analysis, seven of these variables were found to explain 62% (p less than 0.0001) of the variation in the contraceptive behavior of this sample. Poorer contraceptive behavior was associated with noncompliance with the initial birth control method used (33.8%), lower coital frequency (8.3%), older postmenarchial age (5.7%), failure to use birth control at first coitus (4.6%), fewer years dating (4.0%), lower frequency of church attendance (3.3%), and never having experienced a pregnancy scare (2.0%). These findings suggest that the contraceptive behavior of Hispanic female adolescents is a dynamic process that can be understood in the context of previous sexual and contraceptive behavior.


The effect of anthelmintic treatment on helminth infection and anaemia.
A 24-week randomized double blind intervention trial was conducted on adult female tea pluckers from an estate in Bangladesh to investigate the impact of iron supplementation and anthelmintic treatment on changes in ferritin and haemoglobin levels as well as on prevalence and intensity of helminth infections. A total of 553 women were randomly assigned to 1 of 4 intervention groups: group 1 received iron supplementation on a weekly basis, group 2 received anthelmintic treatment at the beginning and half way through the trial, group 3 received both iron supplementation as group 1 and anthelmintic treatment as group 2, and group 4 was a control group and received placebos for both iron supplementation and anthelmintic treatment. Prevalence and intensity of helminth infections (egg counts/g stool) of Ascaris lumbricoides, Trichuris trichiura and hookworms significantly fell in the 2 groups receiving anthelmintic treatment and there were some reductions in the 2 groups not receiving anthelminthic treatment. Haemoglobin and haematocrit concentrations increased significantly in the iron supplemented groups with smaller increases in the anthelmintic only group. All women showed a decrease in serum ferritin levels post-trial with greater losses in the 2 dewormed groups. Significant negative associations were found between hookworm egg counts and ferritin levels and Trichuris trichiura egg counts and haemoglobin concentration.


Mentoring for doctors. Do its benefits outweigh its disadvantages?
Mentoring is widely used in medicine and is an established means of professional development. We have all been mentored, knowingly or otherwise at some stage of our careers. To provide an overview of mentoring in clinical and academic medicine, review the literature, discuss various mentoring styles and weigh the advantages and disadvantages of mentoring. A discussion paper that describes good mentoring, promotes mentoring as a performance enhancer and gives examples to illustrate issues. It draws on available literature and introduces several novel ideas in mentoring. Doctors at all career stages including medical students can benefit from mentoring. Benefits of mentoring include; benefits to the mentee, benefits to the mentor and benefits to the organization. Overall, both mentees and mentors are highly satisfied with mentoring. Nevertheless, problems exist, such as conflict between the mentoring and supervisory roles of the mentor, confidentiality breaches, mentor bias, lack of "active listening" and role confusion. Problems usually stem from poor implementation of mentoring. Mentors should not be the mentee's educational supervisor or line manager or otherwise be involved in their assessment or appraisal to avoid blurring of these distinct roles. Safeguards of confidentiality are of vital importance in maintaining the integrity of the mentoring process. Good mentoring is a facilitative, developmental and positive process which requires good interpersonal skills, adequate time, an open mind and a willingness to support the relationship. Mentors should encourage critical reflection on issues to enable mentees to find solutions to their own problems. Mentoring is an important developmental process for all involved. There is a perception amongst mentors and mentees that well conducted, well timed mentoring can reap enormous benefits for mentees and be useful to mentors and organizations. However strong evidence for this is lacking and there is need for further research in this area.


Single-image-based nonuniformity correction of uncooled long-wave infrared detectors: a deep-learning approach.
Fixed-pattern noise (FPN), which is caused by the nonuniform opto-electronic responses of microbolometer focal-plane-array (FPA) optoelectronics, imposes a challenging problem in infrared imaging systems. In this paper, we successfully demonstrate that a better single-image-based non-uniformity correction (NUC) operator can be directly learned from a large number of simulated training images instead of being handcrafted as before. Our proposed training scheme, which is based on convolutional neural networks (CNNs) and a column FPN simulation module, gives rise to a powerful technique to reconstruct the noise-free infrared image from its corresponding noisy observation. Specifically, a comprehensive column FPN model is utilized to depict the nonlinear characteristics of column amplifiers in the readout circuit of FPA. A large number of high-fidelity training images are simulated based on this model and the end-to-end residual deep network is capable of learning the intrinsic difference between undesirable FPN and original image details. Therefore, column FPN can be accurately estimated and further subtracted from the raw infrared images to obtain NUC results. Comparative results with state-of-the-art single-image-based NUC methods, using real-captured noisy infrared images, demonstrate that our proposed deep-learning-based approach delivers better performances of FPN removal, detail preservation, and artifact suppression.


Single-stage repair of aortic coarctation with ventricular septal defect using isolated cerebral and myocardial perfusion.
To avoid hypothermic circulatory arrest, we have repaired aortic coarctation with ventricular septal defect (VSD) in a one-stage procedure using an isolated cerebral and myocardial perfusion technique, and retrospectively compared this novel approach to the conventional two-stage approach. Between October 1991 and February 1999, 24 infants, aged 4-137 days (median, 27 days) and weighing 1.7-4.3 kg (median, 3.0 kg), underwent the repair of aortic coarctation with VSD either in one (group I, n=11) or two stages (group II, n=13). In Group I, an arterial cannula for cardiopulmonary bypass was inserted into the ascending aorta in six patients with coarctation only, or into a polytetrafluoroethylene (PTFE) graft which was anastomosed to the innominate artery in the remaining five who had hypoplastic arches. A cross-clamp was placed between the innominate and left carotid arteries. The bypass flow was reduced to 30-50% of full flow at 28 degrees C, thereby maintaining a radial artery pressure of 30-45 mmHg. At this point, the aortic coarctation was repaired by an end-to-end arch anastomosis, while maintaining brain perfusion and with the heart still beating. In five patients with hypoplastic aortic arches, the innominate artery proximal to the graft was then secured down and the arch anastomosis was extended to the distal ascending aorta, while providing isolated cerebral perfusion and cardioplegic arrest. After arch reconstruction was performed, the clamp was moved onto the ascending aorta, and the VSD was closed with systemic perfusion. In contrast, for group II patients, coarctation repairs were performed through a posterolateral approach, and existing VSDs were closed as secondary procedures. The mean isolated cerebral and myocardial perfusion time for group I was 13 min (range, 7-20 min). The myocardial ischemic time did not differ between groups I and II (43+/-4 vs. 42+/-5 min, not significant). There were no hospital mortalities or neurological complications in either group, but one late death in each group. Single-stage repair of aortic coarctation with VSD does not increase myocardial ischemic time compared to the traditional two-stage approach. The isolated cerebral and myocardial perfusion technique may offer substantial brain and myocardial protection during aortic arch reconstruction.


Surveillance for dengue and dengue hemorrhagic fever.
Dengue and dengue hemorrhagic fever are emerging as major public health problems in most tropical countries. Effective prevention and control programs will depend on improved surveillance designed to provide early warning of dengue epidemics. This article outlines a reasonable approach to dengue surveillance of this kind. Virologic surveillance should be considered the most important element in any such early warning system. Dengue virus transmission should be monitored to determine which serotypes are present, their distribution, and the type of illnesses associated with each. Other key components of an active surveillance system should include monitoring of fever activity and clinical surveillance for cases of severe and fatal disease associated with viral syndromes. Collectively, these three surveillance components can provide an early warning capability permitting emergency mosquito control measures to be implemented and major epidemics to be averted.


Neutrophilic movement of a Basenji with Pelger-Huët anomaly.
Random and chemotactic neutrophilic movements in a Basenji with Pelger-Huët (P-H) anomaly was compared with such movement in 5 healthy control dogs. Duplicate samples of neutrophils were quantitated after 5, 10, 15, 30, and 45 minutes of incubation. On the basis of population mean responses, no significant difference (P greater than 0.05) was found between P-H and control neutrophils for any type of movement at any time interval examined. These findings indicate that the movement of neutrophils with P-H anomaly may be unaffected by the nuclear abnormality.


[Mortality rate among men aged 40-59 based on the data of intravital screening].
The article compares the results of the screening of 3820 males aged 40 to 59 years, representative of the open population, and the mortality rate over a 6-year-follow-up. Mortality was the highest in males in whom angina pectoris was combined with "ischemic" codes on the ECG and the lowest in subjects without CHD symptoms and without codes of left ventricular hypertrophy. The study showed a fairly high prognostic value of the epidemiologic method of CHD diagnosis.


[Food effects on some reproductive aspects of rainbow trout, Oncorhynchus mykiss, in a Venezuelan fish farm].
Samples of rainbow trout, Oncorhynchus mykiss, were fed with three different dried diets, labeled D1, D2 and D3, the first ones were expanded and the last one pelleted type food. Their protein content ranged from 36% to 42%, and only D1 diet presented a pigment in its composition. The gonodasomatic index (GSI) as well as the gonadial development showed a different behavior in males and females for all the samples tested. A continuous sperm production was observed in males fish, while in female fish the GSI showed a tendency to increase through the whole study, and they showed a reproductive rest period on july 92. Fish relative fecundity and egg diameter were similar in all cases. The gonodial maduration age was shorter for the female that were fed with D1 and D2, while the 50% of the trout population that got D3 had a gonodial maduration period two months longer. For all trouts tested the fertility was low with a maximum value of 49%. The hatchery from the tested trouts with D2 intakes had a mortality value of 62%. Meanwhile, those with D1 and D3 intakes showed mortality values of 36% and 43% respectively.


Metastatic Liposarcoma of the Skull Base: A Case Report and Review of Literature.
Myxoid liposarcoma is not an uncommon form of sarcoma. However, it usually affects the lower extremity long bones. Scapular involvement is extremely rare, as is a metastasis to the parasellar region. We present a case of liposarcoma of the skull base originating in the scapular region and metastasizing to the sellar and parasellar regions and provide a review of the pertinent literature. A 43-year-old female patient diagnosed with left scapular myxoid liposarcoma was treated with surgical resection. She had clear resection margins and was treated pre- and postoperatively with radiotherapy to the region. She remained asymptomatic for 2 years following surgery, after which she abruptly developed diplopia with right lateral gaze. There were no symptoms of raised intracranial pressure or impaired vision. Her examination was normal apart from complete right sixth nerve palsy. Imaging studies of the brain showed a large mass in the clivus eroding into the floor of the sella, encircling the right internal carotid artery in the cavernous sinus. The mass also displaced the sellar contents superiorly. An endonasal, endoscopic skull base approach was undertaken, and a subtotal resection was performed in an effort to avoid multiple cranial nerve pareses. Our literature search revealed that this case report is the first to document liposarcoma metastasis to the skull base originating from the scapular region. Subtotal surgical resection resulted in minimal improvement of the patient's sixth nerve palsy. Postoperative radiation was undertaken. A multidisciplinary approach on an individual patient basis is recommended.


Use of Postpartum Birth Control in Rural Women in Southwest Guatemala: Analysis of a Quality-Improvement Database.
Our objective was to observe the prevalence of postpartum contraceptive use in a population of rural women in Southwest Guatemala by type, and to determine characteristics associated with long-acting reversible contraceptive (LARC) use and sterilization. We conducted a secondary analysis of prospectively collected quality improvement data from a cohort of postpartum women. We compared women intending to use or already using contraception to those not intending to utilize a method; bivariate comparisons were used to determine if there were differences in characteristics between these groups. If differences occurred (p < 0.2), those covariates were included in multivariable regression analyses to determine characteristics associated with use, and then specifically with LARC use and sterilization. In a cohort of 424 women who were surveyed between 2015-2017, the average age was 23 years old, and the prevalence of use or plan to use postpartum contraception was 87.5%. Women with a parity of 2 - 3 were 10% more likely to use any form of postpartum birth control (RR 1.1, CI [1.01, 1.2]) compared to primiparous women. Women who were married were also more likely to use a postpartum method (RR > 10, CI [>10,>10]). The prevalence of LARC use was low (4.0%), and women were more likely to choose this method if they were employed (RR 3.5 CI [1.1, 11.3]).Regarding sterilization, women with a parity of greater than one compared to primiparous women had an increased likelihood of sterilization (RR 3.6 CI [2.5,4.9]); each year a woman aged was associated with a 10% increased likelihood of postpartum sterilization (RR 1.1 CI [1.01,1.08]). Women were also more likely to choose sterilization if delivered by a skilled birth attendant (RR 1.8 CI [1.1,2.9]) or by cesarean birth (RR 2.1 CI [1.4,3.1]). In this cohort, married women of higher parity were more likely to use postpartum contraception, with employed women more likely to use a LARC method. Older women of higher parity who were delivered by a skilled attendant by cesarean birth were the most likely to pursue sterilization.


Developmental toxicity evaluation of methyl tertiary-butyl ether (MTBE) by inhalation in mice and rabbits.
Pregnant CD-1 mice (30 per group) and female New Zealand White rabbits (15 per group) were exposed by inhalation to 0, 1000, 4000 and 8000 ppm methyl tertiary-butyl ether (MTBE) vapor for 6 h a day during gestational days (GD) 6-15 and 6-18, respectively. Maternal body weights, clinical observations and food consumption were recorded throughout gestation for both species. At scheduled euthanization (GD 18 for mice and GD 29 for rabbits), fetuses were weighed, sexed and examined for external, visceral (including craniofacial) and skeletal alterations. For both species, the pregnancy rate was high and equivalent across all groups; no pregnant animals died or aborted. There were no does that delivered early, but there were three mouse dams in the control group and two dams in the 4000 ppm group that delivered early and were removed from the study. In mice, maternal body weights, body weight gain, corrected maternal gestational weight change and food consumption were significantly reduced in mice at 8000 ppm. Hypoactivity and ataxia were observed in dams exposed to 4000 and 8000 ppm. Gestational parameters affected at 8000 ppm included post-implantation loss (due to increased late resorptions and dead fetuses) and altered sex ratio (decreased males); fetal body weights per litter were reduced at 4000 and 8000 ppm. There was a significantly increased incidence of cleft palate at 8000 ppm; this resulted in increased incidences of pooled external and visceral malformations and of total malformations at this exposure concentration. There were also treatment-related increases in the incidence of individual skeletal variations at 4000 and 8000 ppm. In rabbits, maternal weight gain and food consumption were significantly reduced at 4000 and 8000 ppm. Relative liver weights were also reduced at 8000 ppm. All gestational parameters were equivalent across all groups, including pre- and post-implantation loss, fetal sex ratios, litter size and fetal weights/litter. There was no evidence of treatment-related teratogenicity observed at any dose tested in rabbits. The no-observed-effect levels (NOELs) for maternal and developmental toxicity were both 1000 ppm in mice and 1000 ppm and at least 8000 ppm, respectively, in rabbits.


Liver chip and gene shaving.
A comprehensive profile of genes expressed at the mRNA level in various human tissues is considered to be important for understanding the molecular mechanisms of the tissue-specific function and the pathogenesis of related diseases. Here, the gene expression profiling in three human digestive tissues, liver, stomach, and pancreas, was catalogued by generating a large number of expressed sequence tags, and clarified how quantitatively the gene expressions are different. After assembling the redundant clones among three tissues, the results showed that only 1.7% among the assembled genes was expressed commonly in the investigated tissues. These results suggest that the significant functional divergences in different tissues must be related to the divergence of the gene expression profiles. Recently, microarray technologies are widely used. Considering the results that different genes express in different tissues, however, it is important to spot the cDNAs derived from the same tissues or cells examined to acquire information efficiently. For the study of digestive diseases, we constructed an in-house microarray by using the cDNA sets derived from the digestive tissues (liver and gastric chip). In addition, because the amount of information acquired by the microarray analyses is huge, the power of bioinformatics for unifying the obtained data is indispensable. Some examples of the strategies for handling the microarray data obtained by our in-house microarrays are shown in this article.


Evasion of opsonization of macromolecules using novel surface-modification and biological-camouflage-mediated techniques for next-generation drug delivery.
Opsonization plays a pivotal role in hindering controlled drug release from nanoformulations due to macrophage-mediated nanoparticle destruction. While first and second-generation delivery systems, such as lipoplexes (50-150 nm) and quantum dots, hold immense potential in revolutionizing disease treatment through spatiotemporal controlled drug delivery, their therapeutic efficacy is restricted by the selective labeling of nanoparticles for uptake by reticuloendothelial system and mononuclear phagocyte system via various molecular forces, such as electrostatic, hydrophobic, and van der Waals bonds. This review article presents novel insights into surface-modification techniques utilizing macromolecule-mediated approaches, including PEGylation, di-block copolymerization, and multi-block polymerization. These techniques induce stealth properties by generating steric forces to repel micromolecular-opsonins, such as fibrinogen, thereby mitigating opsonization effects. Moreover, advanced biological methods, like cellular hitchhiking and dysopsonic protein adsorption, are highlighted for their potential to induce biological camouflage by adsorbing onto the nanoparticulate surface, leading to immune escape. These significant findings pave the way for the development of long-circulating next-generation nanoplatforms capable of delivering superior therapy to patients. Future integration of artificial intelligence-based algorithms, integrated with nanoparticle properties such as shape, size, and surface chemistry, can aid in elucidating nanoparticulate-surface morphology and predicting interactions with the immune system, providing valuable insights into the probable path of opsonization.


Necessity of Immobilizing the Metacarpophalangeal Joint in Carpometacarpal Osteoarthritis: Short-term Effect.
Conservative treatment for carpometacarpal (CMC) joint osteoarthritis (OA) may include orthotic fabrication to decrease pain. Different types of orthoses have been used as conservative interventions to improve symptoms, but there are no guidelines specifying if inclusion of the thumb metacarpophalangeal (MCP) in an orthosis is required in the treatment of thumb CMC joint OA. The main objective of this study is to determine the effectiveness of 2 different thumb CMC joint orthotic designs on pain reduction and improved hand function: one design immobilizes both the MCP joint and the CMC joint and the other design immobilizes only the CMC joint. A total of 66 patients were included in the study. One group of 33 patients received a short thumb orthosis with the MCP joint excluded, and the other group of 33 patients received a short thumb orthosis with the MCP joint included. Outcomes measures included the visual analog scale for pain and the Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH; Spanish version) for function. In both patient groups, the orthoses contributed to decreased pain levels and improved functional abilities ( F1.0 = 315.467 and F1.0 = 72.419; both, P < .001). There was no significant difference between the 2 groups regarding pain or improvement in daily activities ( F1.0 = 0.553 and F1.0 = 2.539; both, P > .05). There are benefits of either thumb orthotic design on pain reduction and functional improvement even after 1 week of using the orthoses as the sole conservative treatment.


Diagnostic accuracy of 16-slice CT coronary angiography in the evaluation of coronary artery disease.
Multislice CT coronary angiography (CT-CA) has emerged as a potential imaging method for coronary artery disease. This study aimed to ascertain the accuracy of 16-slice CT in the diagnosis of significant coronary stenosis (>or=50% reduction of lumen diameter). This mixed retrospective/prospective observational study compared 95 paired 16-slice CT-CA and fluoroscopic coronary angiography (FCA) sets. A cardiologist and a radiologist blinded to the FCA findings evaluated CT-CA images independently by visual estimation. Disagreement between these reporters was arbitrated by a third CT reporter (a cardiologist). A separate cardiologist blinded to CT-CA findings assessed FCA by visual estimation. Of 1,161 coronary segments assessable on FCA, 1,103 segments (95%) were assessable on CT-CA. The CT-CA correctly diagnosed 147/180 segments with significant stenoses (sensitivity = 82%) and correctly identified 874/923 coronary segments without significant stenoses (specificity = 95%). The positive and negative predictive values of CT-CA in the diagnosis of coronary segment with significant stenosis were 75 and 96%, respectively. On patient-based analysis, CT-CA correctly identified all 68 studies with at least one vessel with significant stenosis (sensitivity = 100%; specificity = 83%). The positive and negative predictive values of CT-CA in identifying patients with significant coronary stenosis were 94 and 100%, respectively. The 16-slice CT-CA showed moderately good sensitivity but very high specificity and negative predictive value in the diagnosis of significant coronary stenosis. The CT-CA would appear to be a useful 'rule-out' test for patients with low-risk profile for ischaemic heart disease.


Pigmented and albino rats differ in their responses to moderate, acute and reversible intraocular pressure elevation.
To compare the electrophysiological and morphological responses to acute, moderately elevated intraocular pressure (IOP) in Sprague-Dawley (SD), Long-Evans (LE) and Brown Norway (BN) rat eyes. Eleven-week-old SD (n = 5), LE (n = 5) and BN (n = 5) rats were used. Scotopic threshold responses (STRs), Maxwellian flash electroretinograms (ERGs) or ultrahigh-resolution optical coherence tomography (UHR-OCT) images of the rat retinas were collected from both eyes before, during and after IOP elevation of one eye. IOP was raised to ~35 mmHg for 1 h using a vascular loop, while the other eye served as a control. STRs, ERGs and UHR-OCT images were acquired on 3 days separated by 1 day of no experimental manipulation. There were no significant differences between species in baseline electroretinography. However, during IOP elevation, peak positive STR amplitudes in LE (mean ± standard deviation 259 ± 124 µV) and BN (228 ± 96 µV) rats were about fourfold higher than those in SD rats (56 ± 46 µV) rats (p = 0.0002 for both). Similarly, during elevated IOP, ERG b-wave amplitudes were twofold higher in LE and BN rats compared to those of SD rats (947 ± 129 µV and 892 ± 184 µV, vs 427 ± 138 µV; p = 0.0002 for both). UHR-OCT images showed backward bowing in all groups during IOP elevation, with a return to typical form about 30 min after IOP elevation. Differences in the loop-induced responses between the strains are likely due to different inherent retinal morphology and physiology.


Individual differences in the acquisition of non-linguistic audio-visual associations in 5 year olds.
Audio-visual associative learning - at least when linguistic stimuli are employed - is known to rely on core linguistic skills such as phonological awareness. Here we ask whether this would also be the case in a task that does not manipulate linguistic information. Another question of interest is whether executive skills, often found to support learning, may play a larger role in a non-linguistic audio-visual associative task compared to a linguistic one. We present a new task that measures learning when having to associate non-linguistic auditory signals with novel visual shapes. Importantly, our novel task shares with linguistic processes such as reading acquisition the need to associate sounds with arbitrary shapes. Yet, rather than phonemes or syllables, it uses novel environmental sounds - therefore limiting direct reliance on linguistic abilities. Five-year-old French-speaking children (N = 76, 39 girls) were assessed individually in our novel audio-visual associative task, as well as in a number of other cognitive tasks evaluating linguistic abilities and executive functions. We found phonological awareness and language comprehension to be related to scores in the audio-visual associative task, while no correlation with executive functions was observed. These results underscore a key relation between foundational language competencies and audio-visual associative learning, even in the absence of linguistic input in the associative task.


Automated COVID-19 diagnosis and classification using convolutional neural network with fusion based feature extraction model.
COVID-19 was first identified in December 2019 at Wuhan, China. At present, the outbreak of COVID-19 pandemic has resulted in severe consequences on both economic and social infrastructures of the developed and developing countries. Several studies have been conducted and ongoing still to design efficient models for diagnosis and treatment of COVID-19 patients. The traditional diagnostic models that use reverse transcription-polymerase chain reaction (rt-qPCR) is a costly and time-consuming process. So, automated COVID-19 diagnosis using Deep Learning (DL) models becomes essential. The primary intention of this study is to design an effective model for diagnosis and classification of COVID-19. This research work introduces an automated COVID-19 diagnosis process using Convolutional Neural Network (CNN) with a fusion-based feature extraction model, called FM-CNN. FM-CNN model has three major phases namely, pre-processing, feature extraction, and classification. Initially, Wiener Filtering (WF)-based preprocessing is employed to discard the noise that exists in input chest X-Ray (CXR) images. Then, the pre-processed images undergo fusion-based feature extraction model which is a combination of Gray Level Co-occurrence Matrix (GLCM), Gray Level Run Length Matrix (GLRM), and Local Binary Patterns (LBP). In order to determine the optimal subset of features, Particle Swarm Optimization (PSO) algorithm is employed. At last, CNN is deployed as a classifier to identify the existence of binary and multiple classes of CXR images. In order to validate the proficiency of the proposed FM-CNN model in terms of its diagnostic performance, extension experimentation was carried out upon CXR dataset. As per the results attained from simulation, FM-CNN model classified multiple classes with the maximum sensitivity of 97.22%, specificity of 98.29%, accuracy of 98.06%, and F-measure of 97.93%.