Unveiling the Enhancement of Spontaneous Emission at Exceptional Points.
Exceptional points (EPs), singularities of non-Hermitian physics where complex spectral resonances degenerate, are one of the most exotic features of nonequilibrium open systems with unique properties. For instance, the emission rate of quantum emitters placed near resonators with EPs is enhanced (compared to the free-space emission rate) by a factor that scales quadratically with the resonance quality factor. Here, we verify the theory of spontaneous emission at EPs by measuring photoluminescence from photonic-crystal slabs that are embedded with a high-quantum-yield active material. While our experimental results verify the theoretically predicted enhancement, they also highlight the practical limitations on the enhancement due to material loss. Our designed structures can be used in applications that require enhanced and controlled emission, such as quantum sensing and imaging.


Block of the mitral-pulmonary isthmus during ablation of a single left-sided accessory pathway causing different patterns of retrograde atrial activation.
The case of a 16-year-old patient with atrioventricular tachycardia caused by a single left anterolateral accessory pathway is reported. When the patient underwent radiofrequency ablation, a lesion on the mitral annulus lateral wall produced changes in the retrograde atrial activation pattern determined by that pathway; changes ranged from a delay in depolarization of the annulus posterior portions to full left atrium counterclockwise activation. Such phenomena were probably caused by a block in the isthmus between the annulus and the lower left pulmonary vein ostium. This case illustrates the importance of the mitral-pulmonary isthmus in the process of left atrium activation, an alert to changes induced by its unintentional block during accessory pathway ablation.


Abdomen and spinal cord segmentation with augmented active shape models.
Active shape models (ASMs) have been widely used for extracting human anatomies in medical images given their capability for shape regularization of topology preservation. However, sensitivity to model initialization and local correspondence search often undermines their performances, especially around highly variable contexts in computed-tomography (CT) and magnetic resonance (MR) images. In this study, we propose an augmented ASM (AASM) by integrating the multiatlas label fusion (MALF) and level set (LS) techniques into the traditional ASM framework. Using AASM, landmark updates are optimized globally via a region-based LS evolution applied on the probability map generated from MALF. This augmentation effectively extends the searching range of correspondent landmarks while reducing sensitivity to the image contexts and improves the segmentation robustness. We propose the AASM framework as a two-dimensional segmentation technique targeting structures with one axis of regularity. We apply AASM approach to abdomen CT and spinal cord (SC) MR segmentation challenges. On 20 CT scans, the AASM segmentation of the whole abdominal wall enables the subcutaneous/visceral fat measurement, with high correlation to the measurement derived from manual segmentation. On 28 3T MR scans, AASM yields better performances than other state-of-the-art approaches in segmenting white/gray matter in SC.


The effects of previous educational training on physical activity counselling and exercise prescription practices among physicians across Nova Scotia: a cross-sectional study.
Physicians (MDs) report difficulty including physical activity (PA) and exercise (PAE) as part of routine care. MDs who report previous educational training in PAE may prescribe exercise more frequently. We evaluated the effects of previous training on perceptions and practices of PA counselling and exercise prescriptions among MDs in Nova Scotia. MDs (n=174) across Nova Scotia completed an online self-reflection survey regarding their current PAE practices. MDs who reported previous training (n=41) were compared to those who reported no training (n=133). Trained-MDs were 22% more confident performing PA counselling than untrained-MDs (p<0.005). In patient appointments, trained-MDs included PAE more often (51% vs 39%; p=0.03) but trained-MDs and untrained-MDs had similar rates of exercise prescriptions (12%; p>0.05). The most impactful barriers (on a scale of 1 to 4) were lack of time (2.5) and perceived patient interest (2.4), which were unaffected by previous training (p>0.05). Previous training was associated with a higher confidence to include PAE discussions with patients by MDs in Nova Scotia, but had minimal influence on their many barriers that prevent exercise prescription. Although some training supports MDs inclusion of PAE into their practice, there is a need for greater, more intensive educational training to assist MDs in prescribing exercise.


Microcalorimetric and SAXS determination of PEO-SDS interactions: the effect of cosolutes formed by ions.
The effect of different ionic cosolutes (NaCl, Na(2)SO(4), Li(2)SO(4), NaSCN, Na(2)[Fe(CN)(5)NO], and Na(3)[Co(NO)(6)]) on the interaction between sodium dodecyl sulfate (SDS) and poly(ethylene oxide) (PEO) was examined by small-angle X-ray scattering (SAXS) and isothermal titration calorimetric techniques. The critical aggregation concentration values (cac), the saturation concentration (C(2)), the integral enthalpy change for aggregate formation (ΔH(agg)(int)) and the standard free energy change of micelle adsorption on the macromolecule chain (ΔΔG(agg)) were derived from the calorimetric titration curves. In the presence of 1.00 mmol L(-1) cosolute, no changes in the parameters were observed when compared with those obtained for SDS-PEO interactions in pure water. For NaCl, Na(2)SO(4), Li(2)SO(4), and NaSCN at 10.0 and 100 mmol L(-1), the cosolute presence lowered cac, increased C(2), and the PEO-SDS aggregate became more stable. In the presence of Na(2)[Fe(CN)(5)NO], the calorimetric titration curves changed drastically, showing a possible reduction in the PEO-SDS degree of interaction, possibility disrupting the formed nanostructure; however, the SAXS data confirmed, independent of the small energy observed, the presence of aggregates adsorbed on the polymer chain.


The duration of atrial fibrillation influences the long-term efficacy of low-energy internal cardioversion.
It is commonly held that long-lasting atrial fibrillation (AF), especially if associated with marked enlargement of the left atrium, is a negative predictive factor for both the recovery and the maintenance of sinus rhythm. The aim of the present study was to identify the clinical features of patients who have a greater likelihood of success both in the acute phase and, especially, in the medium-long term. Since June 1997, we have performed low-energy internal cardioversion to 93 patients (66 males, 27 females, mean age 62 +/- 9 years, range 26-80 years) with a mean duration of AF of 922 +/- 1032 days. Seventy-four patients had heart disease and 19 isolated AF. External cardioversion had been previously performed in 79 patients to no avail. All patients underwent antiarrhythmic therapy and were followed for a period of 13 +/- 7 months. Low-energy internal cardioversion proved efficacious, restoring sinus rhythm, in 92% of patients (86/93) and inefficacious in 8% (7/93). In 24% (21/86) the procedure, although efficacious, was followed by early recurrence of AF which proved to be intractable in 52% (11/21). At the end of the session, 81% (75/93) of the patients maintained sinus rhythm. At the end of follow-up, 40% (38/93) maintained sinus rhythm. Of all the parameters considered in the two groups, the duration of AF was the only one which differed significantly between the group in sinus rhythm and that in AF, with regard to both the efficacy of the procedure in the acute phase (755 +/- 868 vs 1618 +/- 1359 days, p < 0.001) and the long-term outcome (655 +/- 5.8 vs 1107 +/- 1098 days, p < 0.05). AF lasting more than 2 years constitutes a negative predictive factor for both the recovery and the long-term maintenance of sinus rhythm.


Dacryocystitis associated with nasolacrimal duct cyst.
An infant presented with persistent epiphora after successful probing of the lacrimal system. Examination of the nose showed a cystic structure occluding lower portion of the lacrimal drainage system. In cases of recurrent obstruction, nasal examination and endoscopic marsupialization may help guide the clinician towards the most appropriate treatment.


Spectroscopic and saturation magnetization properties of the manganese- and cobalt-substituted Fur (ferric uptake regulation) protein from Escherichia coli.
The Fur apoprotein has been purified and reconstituted with Co2+ and Mn2+ ions. These samples have been analyzed by UV-visible, EPR, and 1H NMR spectroscopies, by XAS, and by magnetization measurements. The apo-Fur protein is able to bind one metal dication (Co2+ or Mn2+) per monomer. A saturation magnetization study confirms the presence of a high-spin metal dication [Mn(II) S = 5/2 and Co(II) S = 3/2]. The two metal ions per Fur dimer are not in magnetic interaction (|J| < 0.1 cm-1 ). The UV-visible spectrum of the cobalt-substituted form (Co-Fur) presents two main bands at 660 nm and 540(br) nm with epsilon540 nm = 65 M-1 cm-1. The EPR spectrum gives the following g values: gx = 5.0(5), gy = 4.0(2), and gz = 2. 3(1), which are in accordance with a nearly axial (E/D < 0.11) site. The value of 55 cm-1 for the splitting (Delta) between the ground and the first excited state has been derived from an EPR saturation study and is in agreement with magnetization data. The EXAFS data of Co-Fur indicate a metal environment comprising five nitrogen/oxygen atoms at 2.11 A, the absence of sulfur, and the presence of histidines as ligands. 1H NMR of Co-Fur in H2O and D2O shows at least two exchangeable signals coming from histidine NH protons and shows the signature of carboxylate group(s). The combined spectroscopic data allow us to propose that the main metal site of Fur in Co-Fur contains at least two histidines, at least one aspartate or glutamate, and no cysteine as ligands and is in an axially distorted octahedral environment.


Prognostic value of Musashi-1 in endometrioid adenocarcinoma.
Musashi-1, a RNA-binding protein, is suggested to be a cancer stem cell-related marker; its high level of protein expression is reported to be associated with high histological grade in some tumors. The aim of this study was to investigate the prognostic value of Musashi-1 in patients with endometrioid adenocarcinoma (EAC). We examined the Musashi-1 mRNA expression level in 35 fresh EAC tissue samples and 15 normal endometrium samples by real-time RT-PCR, and its protein expression level in 148 paraffin EAC tissue samples and 20 paraffin normal endometrium samples by immunohistochemistry. The correlation between Musashi-1 and overall survival (OS) used Cox proportional hazards regression. The prognostic accuracy of Musashi-1 compared with other clinicopathological risk factors by logistic regression. Furthermore, we examined whether Musashi-1 expression is correlated with another cancer stem cell marker CD133 by real-time RT-PCR. Musashi-1 mRNA expression of EAC is 2.8-fold higher than that of normal endometrium (P=0.0009). Musashi-1 protein expression level is correlated with tumor stage, grade and vascular invasion. Patients with higher protein expression level of Musashi-1 are associated with poor survival rate than those with negative or low level of expression (HR=2.073, P=0.001). The area under the curve (AUC) for Musashi-1 is 0.8, which is higher than other clinicopathological factors (P=0.000). In addition, Musashi-1 mRNA expression seems to be closely correlated with CD133 expression (r=0.7167, P<0.0001). Our results suggest high level of Musashi-1 protein expression is associated with poor survival in EAC patients, which may be an independent prognostic factor for EAC.


Combination therapy with interferon alfa-2b and hydroxyurea during the accelerated phase of chronic myelogenous leukemia.
Inferferon alfa-2b (IFN) plays a major role in the current management of previously untreated patients with chronic myelogenous leukemia (CML) as well as patients with CML who have relapsed after bone marrow transplantation. Hydroxyurea (HU) is the best conventional drug for treatment of CML in the chronic phase. Ten patients, six men and four women, 40-70 years of age, were treated during the accelerated phase of CML with a combination of IFN and HU. Patients had received only HU during the chronic phase of the disease. All patients were positive for the Philadelphia chromosome and had an excess number of blasts in peripheral blood smears (more than 10%), as well as increased numbers of basophils and eosinophils but a low leukocyte level of alkaline phosphatase. Eight of them had splenomegaly. Five patients (50%) survived for 1-3 years, achieving complete hematological remission. Three patients had a partial hematological response and died within 1-2 years. Two patients with aggressive disease died within 3 months of the blastic crisis. It appears that combination therapy with IFN and HU might be a useful alternative for patients in the accelerated phase of CML who have failed to respond to HU alone.


Evidence for a major retinitis pigmentosa locus on 19q13.4 (RP11) and association with a unique bimodal expressivity phenotype.
Retinitis pigmentosa (RP) is the name given to a heterogeneous group of retinal degenerations mapping to at least 16 loci. The autosomal dominant form (ARP), accounting for approximately 25% of cases, can be caused by mutations in two genes, rhodopsin and peripherin/RDS, and by at least six other loci identified by linkage analysis. The RP11 locus for adRP has previously been mapped to chromosome 19q13.4 in a large English family. This linkage has been independently confirmed in a Japanese family, and we now report three additional unrelated linked U.K. families, suggesting that this is a major locus for RP. Linkage analysis in the U.K. families refines the RP11 interval to 5 cM between markers D19S180 and AFMc001yb1. All linked families exhibit incomplete penetrance; some obligate gene carriers remain asymptomatic throughout their lives, whereas symptomatic individuals experience night blindness and visual field loss in their teens and are generally registered as blind by their 30s. This "bimodal expressivity" contrasts with the variable-expressivity RP mapping to chromosome 7p (RP9) in another family, which has implications for diagnosis and counseling of RP11 families. These results may also imply that a proportion of sporadic RP, previously assumed to be recessive, might result from mutations at this locus.


Targeting improved patient outcomes using innovative product listing agreements: a survey of Canadian and international key opinion leaders.
To address the uncertainty associated with procuring pharmaceutical products, product listing agreements (PLAs) are increasingly being used to support responsible funding decisions in Canada and elsewhere. These agreements typically involve financial-based rebating initiatives or, less frequently, outcome-based contracts. A qualitative survey was conducted to improve the understanding of outcome-based and more innovative PLAs (IPLAs) based on input from Canadian and international key opinion leaders in the areas of drug manufacturing and reimbursement. Results from a structured literature review were used to inform survey development. Potential participants were invited via email to partake in the survey, which was conducted over phone or in person. Responses were compiled anonymously for review and reporting. Twenty-one individuals participated in the survey, including health technology assessment (HTA) key opinion leaders (38%), pharmaceutical industry chief executive officers/vice presidents (29%), ex-payers (19%), and current payers/drug plan managers/HTA (14%). The participants suggested that ~80%-95% of Canadian PLAs are financial-based rather than outcomes-based. They indicated that IPLAs offer important benefits to patients, payers, and manufacturers; however, several challenges limit their use (eg, administrative burden, lack of agreed-upon endpoint). They noted that IPLAs are useful in rapidly evolving therapeutic areas and those associated with high unmet need, a quantifiable endpoint, and/or robust data systems. The Canadian Agency for Drugs and Technologies in Health, the pan-Canadian Pharmaceutical Alliance, and other arms-length organizations could play important roles in identifying uncertainty and endpoints and brokering pan-Canadian PLAs. Industry should work collaboratively with payers to identify uncertainty and develop innovative mechanisms to address it. The survey results indicated that while challenging, use of IPLAs may be associated with various benefits. Collaboration among stakeholders remains key: Canadian agencies could play an important role in the success of these agreements, while industry should be proactive in offering solutions that will help improve outcomes across the entire health care system.


Quantum study of laser-induced initial activation of graphite-to-diamond conversion.
Recently (Science 2009, 325, 181), femtosecond-resolved electron energy loss spectroscopy (FEELS) was used to map the structural changes of graphite upon laser irradiation, revealing the change from sp(2) to sp(3), i.e., diamond-like, hybridization. With a laser excitation energy of 2.39 eV and a fluence of 1.5 mJ/cm(2), the most pronounced changes were observed in approximately 180 fs, a time similar to the temporal resolution of the technique. The presence of the laser field turns the electronic wavefunction into a wavepacket whose quantum dynamics governs the onset of the structural rearrangement. Density functional theory calculations with a quantum propagator that include the laser field show that the charge density of graphite expands between the layers in an ultrafast process of the order of approximately 10 fs. Calculations as a function of the field/fluence further show different values of the maximum bond order reached at the stationary state. The experimentally used value is at the crossover between two regimes. It is tempting to associate the second regime with the electron organization necessary to achieve ablation or melting. The application of the model demonstrates its potential for examining the dynamical nature of the charge density and chemical bonding as it forms.


[Toxocara canis infection in dogs in Cracow's Shelter for Stray Animals].
A coprologic examination of dogs in Cracow's Shelter for Stray Animals, carried out between January and November 1999-2000 showed that the dogs were infected with Toxocara canis from 2.4% to 16.2%. The puppies were more infected that adult dogs: 30-72.7% and 3,3-12.2% respectively. The females are also more infected than males: 6.3-15.2% and 4.8-18.2% respectively.


Feeding habits of marmosets: A case study of bark anatomy and chemical composition of Anadenanthera peregrina gum.
Primates of the genus Callithrix often obtain exudates from plants of the family Fabaceae. This study characterizes the chemical composition of exudates, and the anatomy and hystochemistry of the secretory ducts in the bark of Anadenanthera peregrina (L.) Speg. var. peregrina (Fabaceae). Exudates from this tree species represent an important component of the diet of hybrid marmosets, Callithrix spp. (Primates: Cebidae). A. peregrina was selected as the focal study tree because it is the only gum tree species exploited by Callithrix groups present within five urban forest fragments in the municipality of Viçosa, Minas Gerais State, Brazil. Gum samples were obtained directly from gouges made by the marmosets, while bark samples were obtained from A. peregrina plants, whether or not they were damaged by the marmosets. Constitutive secretory ducts were present in the bark of ungouged A. peregrina, whereas, marmoset damage caused induced secretory duct formation and an increase in the size of these ducts. The gum produced in the gouges made by the marmosets and in ungouged plants reacted positively to tests for polysaccharides, pectin, mucilage, and proteins. The gum from the gouges exhibited high water (41.0%), carbohydrate (38.2%), protein (19.0%), and mineral (Ca 0.4% and K 0.3%) content. We argue that the relatively high calcium content of A. peregrina gum plays an important nutritional role in, balancing a diet that is otherwise rich in phosphorous and poor in calcium.


[Gel agglutination test--a new test system for semiquantitative detection of feto-maternal transfusion in Rhesus incompatibility].
The postpartum administration of an adequate amount of anti-D immunoglobulin to the mother in cases of Rhesus incompatibility requires the exact quantification of the amount of Rh-positive fetal cells that may be present in the Rh-negative maternal circulation. The classical methods to detect an intrapartum fetomaternal hemorrhage are either time-intensive (such as the Kleihauer-Betke test), of low specificity (such as the indirect Coombs test), or technically cumbersome (such as flow cytometry). The goals of our study were to develop a simple screening test that may be used routinely to quantify fetomaternal hemorrhage in cases of Rhesus incompatability and to evaluate this test in clinical practice. In cases of Rhesus-negative mothers of Rhesus-positive neonates, 2.5 ml of maternal Rhesus negative blood was sampled in an EDTA tubes immediately postpartum and was incubated with anti-D antibodies. Thereafter, a semiquantitative determination was made of the amount of antibody that remained unbound in the serum via a gel agglutination test (GAT) (DiaMed., Switzerland) after mixing with test red blood cells. The amount of anti-D consumed (bound to fetal cells in the first phase) is the semi-quantitatively indicated by the degree of positivity in the second phase the weaker reaction--the more anti-D absorbed in the first phase--the more Rhesus-positive fetal cells present in the maternal sample--the larger the fetomaternal hemorrhage. Following the development of a discrimination zone using this GAT which could ascertain an Rhesus-positive erythrocyte concentration of over 0.2%, the test was applied in a clinical setting. Between September 1995 and April 1998 in unselected postpartum blood samples from 603 Rhesus negative parturients, the GAT was used to test the same blood samples as those requiring evaluation for HbF concentration using the traditional Kleihauer-Betke test. In 585 of the 603 cases (97%) there was no evidence of a fetomaternal transfusion following testing using both methods. Furthermore, both tests showed significant evidence for a fetomaternal transfusion in five cases. The Kleihauer-Betke test was false-positive in three cases of mothers who had a hereditary elevation of the HbF concentration. The GAT showed three false-positive reaction due to a Dweak maternal varient. In two cases, the disparity between the GAT and the Kleihauer-Betke test could be attributed to an antecedant dose of anti-D antibody. In the two cases, the Kleihauer-Betke test results were 0.3% while the GAT was only 0.2%. The GAT may be used as a screening method in routine clinical practice. This is a quick test that allows for the specific determination and semiquantitative evaluation of the Rh-positive erythrocyte concentration in clinically relevant concentrations. Thus, following a positive GAT screening test, a further specific test such as the Kleihauer-Betke test may be utilized to absolutely quantify the amount of blood transfused from fetus to mother. It is also possible to perform such a quantification test with the GAT by eventually using a diluted maternal blood sample.


[The several problems and cautions in treatment of Helicobacter pylori infection].
Helicobacter pylori (H. pylori) infection is the main cause of most gastroduodenal diseases; this discovery has been a major breakthrough in gastroenterology, hematology, dermatology and pediatrics. Triple therapy, including two antibiotics, amoxicillin and clarithromycin, and a proton pump inhibitor given for a week has been recommended as the treatment of choice in guideline for diagnosis and treatment of H. pylori infection in Japanese Journal of Helicobacter Research. However, this treatment may fail for several reasons including bacterial resistance. Our aim to review the problems and cautions in diagnosis and treatment of H. pylori infection.


Seeking control during uncontrollable times: Control abilities and religiosity predict stress during COVID-19.
The COVID-19 pandemic has created an urgent need to understand the protective factors that can buffer individuals against psychological distress. We employed a latent-variable approach to examine how control-related factors such as religiosity, self-control, cognitive control, and health locus of control can act as resilience resources during stressful periods. We found that cognitive control emerged as a protective factor against COVID-19-related stress, whereas religiosity predicted a heightened level of stress. These results provide novel insights into control factors that can safeguard individuals' psychological well-being during crises such as a pandemic.


Direct Oral Anticoagulants for Thromboprophylaxis in Patients with Antiphospholipid Syndrome.
The current mainstay of the treatment and secondary thromboprophylaxis of thrombotic antiphospholipid syndrome (APS) is anticoagulation with warfarin or other vitamin K antagonists (VKAs). In addition to their well-known limitations, VKAs are often problematic in APS patients because of the variable sensitivity of thromboplastins to lupus anticoagulant. As a result, the international normalized ratio may not accurately reflect the intensity of anticoagulation. Direct oral anticoagulants (DOACs) are established as therapeutic alternatives to VKAs for a wide range of indications, including the treatment and secondary prevention of venous thromboembolism. Definition of the role of DOACs in the treatment of thrombotic APS is emerging with the results of recent and ongoing clinical studies. This review focuses on the current situation with regard to DOACs for secondary thromboprophylaxis in APS and issues pertinent to DOAC use in APS patients, as well as potential future directions.


Incidence and Causes of Infusion Alarms in a Neonatal and Pediatric Intensive Care Unit: A Prospective Pilot Study.
To evaluate the incidence and causes of infusion alarms in a NICU/PICU setting. We conducted a 90-day prospective analysis of event logs downloaded daily from infusion pumps (syringe and volumetric pumps). The details about conditions surrounding alarm events were described daily by bedside nurses on a standardized form. The occlusion pressure alarm was set at 300 mm Hg on each device. Forty-one pediatric patients including 12 neonates, mean weight 11.0 ± 11.3 kg (minimum-maximum, 0.48-50), were included for a total infusion time of 2164 hours. Eight hundred forty-three infusion alarms were documented (220 [26.1%] occlusion; 273 [32.4%] infusion completed; 324 [38.4%] door open/syringe disengagement; 26 [3.1%] air-in-line) resulting in an incidence of 4.7 infusion (1.2 occlusion) alarms per patient per day.Detailed conditions surrounding occlusion alarm events were documented in only 22.7% (50/220) of the cases. Of these, 36% (18/50) were related to closed or clamped lines, 4% (2/50) to syringe change, 16% (8/50) to drug injection, and 8% (4/50) to patient-related factors. The remaining 36% (18/50) occurred without any apparent external cause during ongoing infusion, among these drug incompatibilities were a potential cause for 12 events. Alarms from infusion pumps were frequent in the NICU/PICU setting, a quarter of them resulting from line occlusion. Other than well-known triggers (mechanical and patient factors), drug incompatibilities were identified as a potential cause for occlusion alarms in this pilot study.


The impact of patient advisors on healthcare outcomes: a systematic review.
Patient advisory councils are a way for healthcare organizations to promote patient engagement. Despite mandates to implement patient advisory councils through programs like the Patient-Centered Medical Home (PCMH), there is a paucity of data measuring the impact of patients functioning in advisory roles. Our objective is to investigate whether patient engagement in patient advisory councils is linked to improvements in clinical quality, patient safety or patient satisfaction. We searched PubMed, SCOPUS, CINAHL and Google Scholar for English language publications between November 2002 to August 2015, using a combination of "patient advisor" and "care outcomes" search terms. Article selection utilized dual screening facilitated by DistillerSR software, with group discussion to resolve discordance. Observational studies, randomized controlled trials, and case studies were included that described patients serving in an advisory role where primary outcomes were mentioned. Reference lists of included studies and grey literature searches were conducted. Qualitative thematic analysis was performed to synthesize results. Database searching yielded 639 articles total after removing duplicates, with 129 articles meeting full text inclusion criteria. 32 articles were identified for final review, 16 of which were case studies. Advisory roles included patient advisory councils, ad-hoc patient committees, community advisory councils, experience-based co-design, and other. Four practice-based studies from one research group, involving community advisors in the design of public health interventions, found improved clinical outcomes. No prospective experimental studies assessed the impact of patient advisors on patient safety or patient satisfaction. One cluster-randomized RCT showed that patient advisors helped health care planning efforts identify priorities more aligned with the PCMH. Ten case studies reported anecdotal benefit to individual patient advisors. Five included studies demonstrate promising methods for evaluating patient engagement in healthcare delivery and describe impacts on clinical outcomes and priority setting. Based on the case studies found, patient advisors tend to contribute to patient-facing services that may affect clinical care but are not easily evaluated. As clinics and hospitals implement patient advisory councils, rigorous evaluation of their programs is needed to support the expansion of system-level patient engagement. This systematic review was registered in the PROSPERO database of the University of York Centre for Reviews and Dissemination (ID: 2015: CRD42015030020 ).


Sleep-Dependent Anomalous Cortical Information Interaction in Patients With Depression.
Depression is a prevalent mental illness with high morbidity and is considered the main cause of disability worldwide. Brain activity while sleeping is reported to be affected by such mental illness. To explore the change of cortical information flow during sleep in depressed patients, a delay symbolic phase transfer entropy of scalp electroencephalography signals was used to measure effective connectivity between cortical regions in various frequency bands and sleep stages. The patient group and the control group shared similar patterns of information flow between channels during sleep. Obvious information flows to the left hemisphere and to the anterior cortex were found. Moreover, the occiput tended to be the information driver, whereas the frontal regions played the role of the receiver, and the right hemispheric regions showed a stronger information drive than the left ones. Compared with healthy controls, such directional tendencies in information flow and the definiteness of role division in cortical regions were both weakened in patients in most frequency bands and sleep stages, but the beta band during the N1 stage was an exception. The computable sleep-dependent cortical interaction may provide clues to characterize cortical abnormalities in depressed patients and should be helpful for the diagnosis of depression.


Antiviral effects of IFIT1 in human cytomegalovirus-infected fetal astrocytes.
The prominent feature of human cytomegalovirus (HCMV) is cell tropism specificity for human fetal nervous system, which leads to severe fetal nervous system damage especially in first-trimester gestation. In this study, human astrocytes isolated from fetal brain were infected with HCMV AD169 and whole genome transcriptome profile was performed. The results showed that the gene expression of interferon stimulated genes (ISGs), chemokine and chemokine receptors were significantly up-regulated (P < 0.01). The antiviral replication effects of IFIT1 (Interferon-induced protein with tetratricopeptide repeats 1, Fc = 148.17) was investigated. Lentivirus with IFIT1 overexpression or knockdown was transduced into astrocytes, respectively. The viral mRNA, protein expression and HCMV titers were determined. The results showed that IE1, IE2, pp65, and viral titers were significantly decreased in IFIT1 overexpression group and enhanced in the knockdown group compared with control one (P < 0.01). Taken together, this study revealed IFIT1 played an important antiviral role in HCMV infected fetal astrocytes. The prominent feature of human cytomegalovirus (HCMV) is cellular tropism specificity for human fetal brain nervous system leading to severe fetal nervous damage especially in first-trimester gestation. In this study, human astrocytes isolated from first-trimester fetal brain were infected with HCMV AD169 and IFIT1 was studied for its antiviral replication effects. The results provided insights into the function of IFIT1 as a key factor in antiviral defense contributing to development of targeted therapeutics to fetal brain with HCMV infection. J. Med. Virol. 89:672-684, 2017. © 2016 Wiley Periodicals, Inc.


3D culturing and differentiation of SH-SY5Y neuroblastoma cells on bacterial nanocellulose scaffolds.
A new in vitro model, mimicking the complexity of nerve tissue, was developed based on a bacterial nanocellulose (BNC) scaffold that supports 3D culturing of neuronal cells. BNC is extracellularly excreted by Gluconacetobacter xylinus (G. xylinus) in the shape of long non-aggregated nanofibrils. The cellulose network created by G. xylinus has good mechanical properties, 99% water content, and the ability to be shaped into 3D structures by culturing in different molds. Surface modification with trimethyl ammonium beta-hydroxypropyl (TMAHP) to induce a positive surface charge, followed by collagen I coating, has been used to improve cell adhesion, growth, and differentiation on the scaffold. In the present study, we used SH-SY5Y neuroblastoma cells as a neuronal model. These cells attached and proliferated well on the BNC scaffold, as demonstrated by scanning electron microscopy (SEM) and the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium) (MTS) assay. Following neuronal differentiation, we demonstrated functional action potentials (APs) by electrophysiological recordings, indicating the presence of mature neurons on the scaffolds. In conclusion, we have demonstrated for the first time that neurons can attach, proliferate, and differentiate on BNC. This 3D model based on BNC scaffolds could possibly be used for developing in vitro disease models, when combined with human induced pluripotent stem (iPS) cells (derived from diseased patients) for detailed investigations of neurodegenerative disease mechanisms and in the search for new therapeutics.


Exploring the antioxidant effect of Lactobacillus plantarum SCS2 on mice with type 2 diabetes.
This study aimed to evaluate the antioxidant effect of Lactobacillus plantarum SCS2 (L. plantarum SCS2). After 1 week of acclimation, 120 male KM mice were divided into normal group (NG), model group (MG), solvent control group (KG), and different test groups (TG1, TG2, TG3) (n = 20/group) randomly. In the second week, except NG mice, other mice were given 0.2 ml 50 mg/kg (body weight) streptozocin (STZ) through intraperitoneal injection for 5 days. After successful modeling, NG and MG mice were fed normally, KG mice was given 0.5 ml 0.1 mol/L phosphate buffer saline (PBS) per day, TG1, TG2, and TG3 mice were given 0.5 ml suspension, intracellular content and heat-killed intracellular content of L. plantarum SCS2 per day for 9 weeks. Body weight and blood glucose were observed and recorded during intragastric administration. Glucose tolerance levels were measured at the twelfth week, then mice were sacrificed and the serum was collected to measure insulin (INS), glycosylated hemoglobin (HbA1c), malondialdehyde (MDA), reactive oxygen species (ROS) and antioxidant enzymes. The results showed that the reduction of weight loss in TG1 and TG2 mice was observed, which was consistent with the blood glucose. At the same time, the INS level of TG1, TG2, and TG3 mice were increased and the HbA1c levels were decreased. Otherwise, the MDA and ROS content in the serum of TG1, TG2, and TG3 mice were decreased and the level of antioxidant enzymes was increased. Interestingly, the activity and content of antioxidant enzymes in TG2 group was the highest in the three test groups. PRACTICAL APPLICATIONS: The results of this study showed that L. plantarum SCS2 could effectively reduce blood glucose, relieve weight loss, improve INS deficiency, and also improve oxidative stress by increasing the activity of antioxidant enzymes. The findings suggest that L. plantarum SCS2 could improve diabetes-related symptoms by alleviating oxidative stress. In the future, people could promote the application of lactic acid bacteria (LAB) which is found in traditional foods with the ability of improving oxidative damage in food nutrition and related fields, so as to guide residents to form good dietary habits, and effectively prevent type 2 diabetes. Meanwhile, it also can enhance the edible value of traditional foods.


Purpose in life and cognitive functioning in adulthood.
With an increasingly aging population, more work is needed to identify factors which may promote the maintenance of normal cognitive functioning. The current study tested the concurrent association between sense of purpose in life and the cognitive variables of episodic memory, executive functioning, and composite cognitive functioning in adults (N = 3489, Mage = 56.3 years, SD = 12.27, Range = 32-84 years) from the Midlife in the United States study (MIDUS). Correlational analyses suggested that purpose in life was associated with higher scores for memory, executive functioning, and overall cognition. Bootstrapping tests of moderation found no evidence for a moderating effect of age on purpose and the cognitive variables. Future studies should attempt to explain the mechanisms behind this relationship and explore the potential for interventions to promote healthy cognitive and purposeful aging.


MRI of pregnancy-related issues: abnormal placentation.
In this article, we review the clinical significance of abnormal placentation and the role of MRI in diagnosis and management of this potentially morbid condition. We present our clinical perspective on diagnosing this challenging problem with MRI and review the imaging findings that can lead to a correct diagnosis. As abnormal placentation becomes more prevalent, in large part due to the markedly rising rates of cesarean delivery, there is a need for accurate antenatal diagnosis of this condition to prevent maternal morbidity and mortality. Maternal and fetal outcomes can be optimized through multidisciplinary planning to achieve accurate diagnosis and anticipation of the extent of abnormal placentation in the antenatal period. Imaging findings of abnormal placentation have been described for both ultrasound and MRI, although limitations exist for each technique. Although ultrasound remains the primary screening modality for the detection of abnormal placentation, MRI is a complementary technique that should be considered when ultrasound is inconclusive or incomplete. Familiarity with MRI techniques to assess the placenta, MRI appearance of normal placenta, and imaging findings that suggest abnormal placentation can help radiologists contribute to a successful maternal outcome.


Investigation of Structural and Optical Properties of Some [1,4]Dithiine-porphyrazine Dyes.
1,4-Bis(p-tolylamino)-6,7-dichloroanthraquinone 1 when reacted with di(sodiothio)-maleonitrile 2 afforded heterocyclic thianone compound, 5,12-dioxo-5,12-dihydroanthro[2,3-b][1,4]dithiine-2,3-dicarbonitrile 3. Using lithium/pentanol and acetic acid, the dicarbonitrile product 3 was cyclotetramerized, yielding the matching tetra 5,12-dioxo-5,12-dihydroanthro[2,3-b][1,4]dithiine-porphyrazine dye compound (2H-Pz) 4a. The dicarbonitrile molecule was a ring-shaped metallic product utilizing metallic salt and quinoline, yielding the corresponding tetra 5,12-dioxo-5,12-dihydroanthro[2,3-b][1,4]dithiine-porphyrazinato-metal II dyes (M-Pz), M = Zn, Co, or Ni 4b-d. The produced compounds' elemental analysis investigation, Infrared, and nuclear magnetic resonance spectrum information accord with the structures attributed to them. The cyclotetramerization and complexation reactions are ensured by the molecular weight and metal load of the produced products. The inclusion of electron-donating groups resulted in a lower optical band gap of the produced dye sensitizers, with "push-pull" promotion of about 1.55 eV. The prepared substituted porphyrazines reveal high absorption in the UV-VIS region, which could be of potential value as a building block for novel electronic and optical materials as well as a sensor for technology. This is considered for improving solar cell absorption. The absorption bands of the synthesized porphyrazine dyes extend beyond 800 nm, so these dyes could be useful in various optoelectronic applications.


Prospective evaluation of a novel one-stop testicular clinic.
In 2003, the waiting time for routine scrotal assessment approached 6 months in our hospital. The patients' diagnostic pathway was not uniform and involved several delays between general practitioner, radiologist and urologist. If malignancy was suspected, patients were seen and assessed within 2 weeks. However, it was possible for patients with unsuspected malignancy to have their diagnosis delayed. Funding was provided by the NHS Modernisation Agency's Action On Urology project. Men who were referred by their general practitioner (GP) with a testicular or scrotal condition would be reviewed in a one-stop joint sonographer and urology nurse specialist clinic provided entirely within the urology department with rapid open access. Data were prospectively collected for 2 years. Source of referral, suspected diagnosis, findings and outcome were recorded. A total of 1017 patients attended the clinic over this period; of these, 203 (4%) were referred under the '2-week wait' criteria. Of patients attending the clinic, 79% were discharged to GP care, 8% were added to the waiting list for a surgical procedure and 20% were referred with 'testicular lump'. Eleven patients were suspected to have testicular tumour on ultrasound and proceeded to orchidectomy in this period. One patient (0.1%) was found to have an unsuspected seminoma. The waiting time for all scrotal ultrasound examinations has fallen from 22 to 2 weeks. The waiting times for intravenous urography and general ultrasound were also significantly reduced following the introduction of this service (P = 0.005). The majority of patients passing through this clinic are the 'worried-well' with benign scrotal pathology. They can now be seen within 2 weeks regardless of whether their GP suspects testicular tumour. This reduces anxiety in this large group of patients freeing capacity elsewhere in the diagnostic imaging department.


Management of whiplash-associated disorder in the Italian emergency department: the feasibility of an evidence-based continuous professional development course provided by physiotherapists.
The management of whiplash and associated disorders (WAD) in the Italian Health System is still empirical and influenced by a single professional's expertise. Therefore, the purpose of our study is to describe a structured management changes in an Italian emergency department (ED) after an evidence based continuous professional development (CPD) course. A CPD course was organized by Orthopedic Manipulative Physical Therapists (OMPT) for personnel of ED in the hospital Girolamo Fracastoro (San Bonifacio, Verona, Italy), based on latest scientific evidence. Data regarding the number of X-Rays, computed tomography (CT) scan, orthopaedic referrals, neck collars and WAD IV (i.e., severe diagnosis) before and after the course were compared. 3066 cases of WAD have been analyzed in 2016 and 2185 in 2017/2018. The number of X-Rays dropped down from 15.1% to 13.5%; the CT scans increased from 1.3% to 1.9%; the WAD IV diagnosis increased from 0.7% to 1.6%; the orthopaedic referrals dropped from 1.5% to 1.1%; the collars prescription dropped from 8.8% to 2.5%. An updated framework increased the efficiency of ED's maintaining the same level of safety (i.e., WAD IV diagnosis). Given that, it can also be argued that, in line with other countries, the implementation of an OMPT role within the ED multidisciplinary team is advised also in Italy.Implications for rehabilitationPhysiotherapists were commissioned to organize a management change of patients in an Italian Emergency Department clinical setting for the management of whiplash;Guidelines and other appropriate clinical rules facilitate the delivery of an evidence-based and more appropriate management and care plan;An inter-disciplinary continuous professional development course has the potential to positively influence patients' journey and to optimize the use of departmental resources;The involvement of other health professionals (e.g., Physiotherapists) within the Italian Emergency Department organizational chart might lead to further improvement of service provided.


Data Quality in the Human and Environmental Health Sciences: Using Statistical Confidence Scoring to Improve QSAR/QSPR Modeling.
A greater number of toxicity data are becoming publicly available allowing for in silico modeling. However, questions often arise as to how to incorporate data quality and how to deal with contradicting data if more than a single datum point is available for the same compound. In this study, two well-known and studied QSAR/QSPR models for skin permeability and aquatic toxicology have been investigated in the context of statistical data quality. In particular, the potential benefits of the incorporation of the statistical Confidence Scoring (CS) approach within modeling and validation. As a result, robust QSAR/QSPR models for the skin permeability coefficient and the toxicity of nonpolar narcotics to Aliivibrio fischeri assay were created. CS-weighted linear regression for training and CS-weighted root-mean-square error (RMSE) for validation were statistically superior compared to standard linear regression and standard RMSE. Strategies are proposed as to how to interpret data with high and low CS, as well as how to deal with large data sets containing multiple entries.


Morphologic and functional remodeling of the right ventricle in pulmonary hypertension by real time three dimensional echocardiography.
The aims of this study were to assess the right ventricle in different causes of pulmonary hypertension (PH) and to assess the changes of the tricuspid apparatus during this remodeling. The functional and morphologic changes of the right ventricle and the tricuspid apparatus in relation to different causes of PH remain elusive. A total of 141 consecutive patients were prospectively recruited, of whom 55 had pulmonary arterial hypertension (PAH), 32 had chronic thromboembolic disease (CTED), and 34 had PH secondary to mitral regurgitation (MR). Twenty age- and gender-matched healthy volunteers were also studied to serve as controls. Real-time 3-dimensional echocardiography was used to assess right ventricular (RV) volumes and tricuspid valve mobility. Overall, RV diastolic volumes were greater and RV ejection fractions lower in patients with PAH compared to those with CTED and MR (186.4 ± 48.8 vs 113.5 vs 109.4 ml, p < 0.001, and 33.2% vs 36.8% vs 66.8%, p < 0.001, respectively). Among the 3 PH groups, tricuspid valve mobility was most restricted in the CTED group and least restricted in the MR group. Tricuspid tenting volume was greater in the CTED and PAH groups than in the MR group (p < 0.01). Most patients with PAH (54.6%) had at least moderate tricuspid regurgitation, while in the CTED group, most (59.4%) had mild and only 37.5% had moderate tricuspid regurgitation (p < 0.01). Conversely, patients with MR (85%) had only mild tricuspid regurgitation. There was no correlation between RV systolic pressures and the RV ejection fraction or tenting volume. In conclusion, this study demonstrates that different causes of PH may lead to diverse RV remodeling, with the most adverse remodeling being in patients with PAH. In addition, changes of the tricuspid apparatus also differed, with the most adverse effects seen in patients with CTED.


Size of the associations between anticholinergic burden tool scores and adverse outcomes in older patients.
Background Several anticholinergic scales and equations to evaluate the anticholinergic burden have been previously created. Association of these instruments with the anticholinergic outcomes are usually estimated by means of hypothesis contrast tests, which ignore the size of the association effect. Objective To evaluate the effect size of the associations between the scores on cumulative anticholinergic burden instruments with peripheral or central anticholinergic adverse outcomes in older patients. Setting Internal medicine ward of a Tertiary University Hospital. Methods A case-control study was conducted in patients over 65 years who were admitted to two internal medicine wards of a Portuguese university hospital. The Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden scale and Drug Burden Index were used to calculate the patients' anticholinergic burden. Peripheral (dry mouth-swab technique; dry eye-Schirmer test) and central (falls and cognitive impairment-Mini-Mental State Examination) anticholinergic adverse outcomes were investigated. The Barthel Index was used to assess overall physical functionality. The Mann-Whitney test was used to evaluate probabilistic differences in the anticholinergic scores between case and control individuals. To establish the effect size of the associations, the area under the curve of the receiver operating characteristics curve was calculated. Main outcome measure Anticholinergic adverse effects. Results A total of 250 patients (mean age 81.67 years, standard deviation 7.768; 50% females) were included. In total, 148 patients (59.2%) presented with dry mouth, 85 (34%) with dry eye, 141 (56.4%) with impaired functionality, 44 (17.6%) with a history of falls and 219 (87.6%) with cognitive impairment. Significant differences (p < 0.05) were obtained for the majority of the associations between Anticholinergic Drug Scale, Anticholinergic Risk Scale, Anticholinergic Cognitive Burden and Drug Burden Index and adverse effects. Conversely, the effect sizes of these associations ranged from "fail" (area under the curve 0.5 to 0.6) to "fair" (area under the curve 0.7 to 0.8). Conclusion Although significant differences in the scores of anticholinergic burden instruments and adverse outcomes may exist, the effect sizes of these associations ranged from 'fail' to 'fair', which limits their utility in preventing anticholinergic adverse outcomes with medication review interventions.


Acute poststreptococcal glomerulo-nephritis in general practice: the contribution of infection to its onset and course.
Twenty-one patients considered to have acute poststreptococcal glumerulo-nephritis were encountered during 35 years of general practice. In ten of them good evidence of active streptococcal infection at the time of discovery of nephritis was recorded. The more complete the data the more convincing was the evidence of active infection. In over half of those whose urine were routinely cultured pathogens were isolated and over a third were treated for infection of the urinary tract. Such infections were associated with adverse effects and prolonged illness. As compared with children, adults in general had a longer history of ill-health, were less likely to present with acute infections and more likely to have urinary tract infections and prolonged illness. Vigorous antistreptococcal treatment was followed by rapid recovery in those patients so treated whose illnesses were not complicated by urinary tract infections. Concurrent streptococcal infection and secondary infection of the urinary tract may contribute more to the onset of acute poststreptococcal glomerulo-nephritis and to its course than is currently believed.


New approach to probability estimate of femoral neck fracture by fall (Slovak regression model).
3,216 Slovak women with primary or secondary osteoporosis or osteopenia, aged 20-89 years, were examined with the bone densitometer DXA (dual energy X-ray absorptiometry, GE, Prodigy - Primo), x = 58.9, 95% C.I. (58.42; 59.38). The values of the following variables for each patient were measured: FSI (femur strength index), T-score total hip left, alpha angle - left, theta angle - left, HAL (hip axis length) left, BMI (body mass index) was calculated from the height and weight of the patients. Regression model determined the following order of independent variables according to the intensity of their influence upon the occurrence of values of dependent FSI variable: 1. BMI, 2. theta angle, 3. T-score total hip, 4. alpha angle, 5. HAL. The regression model equation, calculated from the variables monitored in the study, enables a doctor in praxis to determine the probability magnitude (absolute risk) for the occurrence of pathological value of FSI (FSI < 1) in the femoral neck area, i. e., allows for probability estimate of a femoral neck fracture by fall for Slovak women. 1. The Slovak regression model differs from regression models, published until now, in chosen independent variables and a dependent variable, belonging to biomechanical variables, characterising the bone quality. 2. The Slovak regression model excludes the inaccuracies of other models, which are not able to define precisely the current and past clinical condition of tested patients (e.g., to define the length and dose of exposure to risk factors). 3. The Slovak regression model opens the way to a new method of estimating the probability (absolute risk) or the odds for a femoral neck fracture by fall, based upon the bone quality determination. 4. It is assumed that the development will proceed by improving the methods enabling to measure the bone quality, determining the probability of fracture by fall (Tab. 6, Fig. 3, Ref. 22). Full Text (Free, PDF) www.bmj.sk.


[Trends in population aging].
The age structure of the world population between 1950 and 1985 is analyzed according to changes in fertility, mortality, and international migration in developing and developed countries. "Relying on the results of the medium scenario of the population forecasts prepared by the U.N. Division of International Economic and Social Affairs, the author demonstrates that aging of the world population will become a global phenomenon, characteristic of every region and county of the world, between 1985 and 2025." (SUMMARY IN ENG AND RUS)


23 gauge pars plana vitrectomy for the removal of retained intraocular foreign bodies.
To evaluate the morpho-functional outcomes and safety of transconjuctival 23-gauge pars plana vitrectomy(PPV) for removal of intraocular foreign bodies (IOFBs). A retrospective study of 36 consecutive cases (mean age; 34,2 ± 10,9 years (between 15 and 60), 27 M,9 F) of 23-G PPV for the removal of IOFBs during the period of April 2009 and December 2011 and followed 9,4 ± 6,4(2-27) months were conducted. Visual outcomes, slit lamp biomicroscopy, intraocular pressure (IOP), and posterior segment visualization by indirect ophthalmoscopy, A-B mode ultrasonography, and computed orbital tomography were performed for all cases. Main outcomes including anatomic and visual outcomes, and both intraoperative and postoperative complications were recorded. Of the 36 cases available for the study, the IOFBs (size range, 3 to 12 mm) could be removed in all eyes. Mean preoperative LogMAR BCVA was 1.44 ± 138 (range, 1.00 to 0.00) and mean postoperative LogMAR BCVA at final visit was 0,78 ± 0,98 (range, 1.00 to 0.00). (P = 0,007) Anatomic success was obtained in 97.2 % of eyes. 16 patients needed primary wound repair due to the leakage in insertion sites before the PPV, however remaining 20 cases were not. Fibrin reaction was seen in 8 (22.2 %) patients in early postoperative period, intraocular pressure elevation was detected in 12 (33.3 %) patients in which the silicone oil was used as an intravitreal tamponade, one patient with silicone oil tamponade developed band keratopathy and phthisis bulbi. 23-Gauge PPV is a feasible, effective approach in the surgical management of the patients with posterior segment intraocular foreign bodies.


A Mini-Review on Chitosan-Based Hydrogels with Potential for Sustainable Agricultural Applications.
Agriculture is an important sector of the economy, but this industry consumes significant amounts of water, which is a precious and limited natural resource. Irrigation techniques and efforts to mitigate water usage influence the growth, survival, and yield of crops. However, superabsorbent polymers in combination with fertilizers can be employed to obtain sustained release of nutrients and improved water retention capacity of the soil. Despite significant recent progress in this area involving synthetic polyacrylate hydrogels, there are no industrially applicable solutions exhibiting similar performance using natural biopolymers or synthetic polymers enriched with natural components. This review focuses on biodegradable chitosan-based hydrogels (both natural and semi-synthetic), and discusses their potential agricultural and horticultural applications. The methods for synthesizing hydrogels via physical or chemical crosslinking, and the resulting functional properties of recently reported hydrogels, such as water retention and release of active ingredients, are presented herein.


Is microrheometry affected by channel deformation?
Microrheometry is very important for exploring rheological behaviours of several systems when conventional techniques fail. Microrheometrical measurements are usually carried out in microfluidic devices made of Poly(dimethylsiloxane) (PDMS). Although PDMS is a very cheap material, it is also very easy to deform. In particular, a liquid flowing in a PDMS device, in some circumstances, can effectively deform the microchannel, thus altering the flow conditions. The measure of the fluid relaxation time might be performed through viscoelasticity induced particle migration in microfluidics devices. If the channel walls are deformed by the flow, the resulting measured value of the relaxation time could be not reliable. In this work, we study the effect of channel deformation on particle migration in square-shaped microchannel. Experiments are carried out in several PolyEthylene Oxyde solutions flowing in two devices made of PDMS and Poly(methylmethacrylate) (PMMA). The relevance of wall rigidity on particle migration is investigated, and the corresponding importance of wall rigidity on the determination of the relaxation time of the suspending liquid is examined.


[Predictive value of the study of cerebro-spinal fluid in neurological diseases. Discriminant analysis of 733 cases].
The study of cerebrospinal fluid (CSF) gives very valuable data for the diagnosis of certain neurological disorders. Objective. To discover the discriminative value of different tests and their usefulness in the study of neurological disorders. Discriminative multivariate analysis was used for the group of parameters obtained from study of CSF and serum in a sample of 733 patients. BO was included, CSF cytobiochemical data and five of the equations used for calculation of the synthesis of intrathecal IgG. The best discriminative function was expressed as the intrathecal IgG with normal BHE. The formula of Tourtellotte was noteworthy for overestimation of the synthesis of intrathecal IgG when the albumin index indicated BHE rupture. Prospective reclassification of the 733 cases showed that these tests are well worthwhile to rule out immunologically mediated disorders (93% of the cases were correctly reclassified); they suggest the diagnosis in multiple sclerosis (66% correctly reclassified) and give very poor reliability when trying to distinguish between inflammatory infectious processes. In spite of their undoubted use in supporting the clinical diagnosis, the tests used for study of the synthesis of IgG, even complemented by cytobiochemical examination of the CSF, are not in themselves sufficient for use as a discriminative test in the differential diagnosis of neurological processes.


Development of an oral drug delivery system targeting immune-regulating cells in experimental inflammatory bowel disease: a new therapeutic strategy.
Several studies have indicated the involvement of macrophages and dendritic cells in active inflammatory bowel disease (IBD). Manipulation of these cells is considered a very important therapeutic strategy for patients with IBD. We evaluated the effect of a new drug delivery system targeting microfold cells and macrophages with poly(DL-lactic acid) microspheres containing dexamethasone (Dx). Colitis was induced in BALB/c mice by 5% dextran sodium sulfate. Dx microspheres (n = 10) and only Dx (n = 10) were orally administered to dextran sodium sulfate-treated mice. Thereafter, serum levels and tissue distributions of Dx were investigated. To estimate the efficacy of this drug delivery system, we measured the histological score, myeloperoxidase activity and nitric oxide production, and gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma in the colonic tissue. Serum Dx levels were not increased after oral administration of Dx microspheres. The tissue distribution of microspheres containing (125)I-labeled Dx in inflamed colon was significantly higher than in other organs. The histological score, myeloperoxidase activity, and nitric oxide production of the group treated with Dx microspheres were significantly lower than of those treated with Dx alone. Gene expressions of tumor necrosis factor-alpha, interleukin-1beta, and interferon-gamma were down-regulated in mice treated with Dx microspheres. Microspheres containing glucocorticoids such as Dx, which target microfold cells and macrophages, can facilitate mucosal repair in experimental colitis and could be an ideal agent for treatment of human IBD.


A π-extended triphenylamine based dopant-free hole-transporting material for perovskite solar cells via heteroatom substitution.
The triphenylamine (TPA) group is an important molecular fragment that has been widely used to design efficient hole-transporting materials (HTMs). However, the applicability of triphenylamine derived HTMs that exhibit low hole mobility and conductivity in commercial perovskite solar cells (PSCs) has been limited. To aid in the development of highly desirable TPA-based HTMs, we utilized a combination of density functional theory (DFT) and Marcus electron transfer theory to investigate the effect of heteroatoms, including boron, carbon, nitrogen, oxygen, silicon, phosphorus, sulfur, germanium, arsenic, and selenium atoms, on the energy levels, optical properties, hole mobility, and interfacial charge transfer behaviors of a series of HTMs. Our computational results revealed that compared with the commonly referenced OMeTPA-TPA molecule, most heteroatoms lead to deeper energy levels. Furthermore, these heteroatom-based HTMs exhibit improved hole mobility due to their more rigid molecular structures. More significantly, these heteroatoms also enhance the interface interaction in perovskite/HTM systems, resulting in a larger internal electric field. Our work represents a new approach that aids in the understanding and designing of more efficient and better performing HTMs, which we hope can be used as a platform to propel the developmental commercialization of these highly desirable PSCs.


[Finite element analysis of lumbar facet joint contact model].
To establish a finite element model of the fourth and fifth lumber segments in order to analyze the biomechanical characteristics of facet joints under different pressure loads. CT sectional images of L(4-5) segments were obtained to construct a finite element model, adopting contact model to simulate the condition the superior and inferior facets were in. The facet joint exhibited different performances under different conditions, and more loads was forced on it when the model was twirled. The facet joints should be simulated as in condition of contact to help correct understanding of the biomechanical characteristics of the spinal segment.


Determining the release kinetics of risperidone controlled release matrices to treat schizophrenia.
Risperidone is an atypical antipsychotic agent clinically used to treat schizophrenia, bipolar diseases, and autism. Usually, the frequency of doses is twice daily. In the present study, risperidone controlled release matrices formulated using hydrophilic and hydrophobic polymers. The tablets were prepared by direct compression. The pre-compression and post-compression properties were assessed, along with swelling studies. The morphology of particles observed using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FT-IR). The stability study on the drug was performed using thermal gravimetric analysis (TGA) and differential thermal analysis (DTA). The optimized formulation was prepared with the help of hydrophilic polymer K100M (40% ratio). Furthermore, release kinetics had investigated. The release pattern of optimized formulation FT5 fitted best to zero-order kinetics and showed excellent release characteristics. The model-independent approach had been used, formulations FT6 and FT8 showed resemblance with FT5 in all three media, respectively. The once daily formulation of risperidone could be beneficial for schizophrenia patients and their caregivers and will improve patient compliance.


The myogenic electric organ of Sternopygus macrurus: a non-contractile tissue with a skeletal muscle transcriptome.
In most electric fish species, the electric organ (EO) derives from striated muscle cells that suppress many muscle properties. In the gymnotiform Sternopygus macrurus, mature electrocytes, the current-producing cells of the EO, do not contain sarcomeres, yet they continue to make some cytoskeletal and sarcomeric proteins and the muscle transcription factors (MTFs) that induce their expression. In order to more comprehensively examine the transcriptional regulation of genes associated with the formation and maintenance of the contractile sarcomere complex, results from expression analysis using qRT-PCR were informed by deep RNA sequencing of transcriptomes and miRNA compositions of muscle and EO tissues from adult S. macrurus. Our data show that: (1) components associated with the homeostasis of the sarcomere and sarcomere-sarcolemma linkage were transcribed in EO at levels similar to those in muscle; (2) MTF families associated with activation of the skeletal muscle program were not differentially expressed between these tissues; and (3) a set of microRNAs that are implicated in regulation of the muscle phenotype are enriched in EO. These data support the development of a unique and highly specialized non-contractile electrogenic cell that emerges from a striated phenotype and further differentiates with little modification in its transcript composition. This comprehensive analysis of parallel mRNA and miRNA profiles is not only a foundation for functional studies aimed at identifying mechanisms underlying the transcription-independent myogenic program in S. macrurus EO, but also has important implications to many vertebrate cell types that independently activate or suppress specific features of the skeletal muscle program.


Revascularization of an ischemic limb by use of a muscle pedicle flap: a rabbit model.
A rabbit model of hind limb ischemia was designed to demonstrate that new, hemodynamically significant arterial connections will develop between ischemic skeletal muscle and an independently perfused muscle pedicle flap. The right common iliac artery was divided in 15 rabbits. In eight rabbits a muscle flap based on the left deep inferior epigastric artery was transposed to the right thigh (flap group). In seven rabbits a sham operation was performed where the flap was sutured to the abdominal wall (sham group). After 7 days angiography demonstrated arterial connections between the flap and the native limb circulation in all of the flap group animals. The flap increased muscle perfusion in the ischemic limb (2.99 ml/100 gm muscle/minute in the flap group, vs 2.06 ml/100 gm muscle/minute in the sham group, p less than 0.005). Hemodynamically significant vascular connections will develop between a well-perfused muscle flap and an ischemic limb. The augmentation in perfusion provided by these connections can be quantified.


Multiple structures and dynamics of [CpRu(CO)2]2 and [CpFe(CO)2]2 in solution revealed with two-dimensional infrared spectroscopy.
Two-dimensional infrared (2DIR) spectroscopy is applied to both (Cp)(2)Fe(2)(CO)(4) and its ruthenium analog (Cp)(2)Ru(2)(CO)(4) in order to study the vibrational dynamics of these two systems. Combining the results of 2DIR spectroscopy and DFT calculations, the different structural forms of both the iron and the ruthenium complexes were characterized, furthering the previous assignment of the linear IR spectrum by determining the transition frequencies associated with the different isomeric forms. Monitoring the time-dependent amplitudes of the cross peaks enabled the observation of equilibrium energy transfer dynamics between different vibrational modes of the cis-B (Cp)(2)Fe(2)(CO)(4) and the gauche-NB (Cp)(2)Ru(2)(CO)(4) complexes. Treating the energy transfer as an equilibrium process, we extracted the rate constants associated with both the uphill and the downhill transfer of vibrational energy, finding that the difference in the rate constants of the two metal complexes maps to the difference in the energy gap between the two modes involved.


Impact of one and two human papillomavirus (HPV) vaccine doses on community-level HPV prevalence in South African adolescent girls: study protocol and rationale for a pragmatic before-after design.
Vaccines against human papillomavirus (HPV) are the key to controlling cervical cancer in low/middle-income countries (LMICs) where incidence is highest, but there have been limited data from these settings on programme impact on HPV prevalence, and none in a population with endemic HIV infection. Furthermore, for many LMICs, the currently recommended two-dose schedule is difficult to deliver at scale, so there is mounting interest in a single-dose schedule. The Human Papillomavirus One and Two-Dose Population Effectiveness Study is a hybrid impact evaluation of the national South African HPV vaccination programme, which has targeted grade 4 girls aged at least 9 years in public schools with two doses of vaccine since 2014, and a single-dose vaccine 'catch-up' programme delivered in one district in 2019. Impacts of both schedules on the prevalence of type-specific HPV infection will be measured using repeat cross-sectional surveys in adolescent girls and young women aged 17-18 years recruited at primary healthcare clinics in the four provinces. A baseline survey in 2019 measured HPV prevalence in the cohort who were ineligible for vaccination because they were already above the target age or grade under either the national programme or the single-dose programme in the selected district. HPV prevalence surveys are repeated in 2021 in the selected district, and in 2023 in all four provinces. We will calculate prevalence ratios to compare the prevalence of HPV types 16 and 18 in the single-dose (2021) and two-dose (2023) cohorts, with the vaccine-ineligible (2019) cohort. The project was approved by the University of the Witwatersrand Human Research Ethics Committee (HREC #181005), and the University of New South Wales HREC (#181-005). Findings will be disseminated through peer-reviewed journals, scientific meetings, reports and community forums.


Genistein Regulates Lipid Metabolism via Estrogen Receptor β and Its Downstream Signal Akt/mTOR in HepG2 Cells.
Genistein (GEN) has been shown to significantly inhibit hepatic triglyceride accretion triggered by estrogen deficiency. The main purpose of this in vitro study was to investigate the function and molecular mechanism of estrogen receptor β (ERβ) in regulating hepatic lipid metabolism induced by GEN. Different doses of GEN or GEN with an ERβ antagonist were treated with HepG2 cells. Results showed that 25 μM GEN significantly diminished triglyceride levels. Meanwhile, GEN downregulated the levels of genes and proteins involved in lipogenesis, such as sterol-regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FASN), and stearoyl-coenzyme A desaturase 1 (SCD1), and upregulated the gene and protein levels of the regulation factors responsible for fatty acid β-oxidation, such as carnitine palmitoyltransferase 1α (CPT-1α) and peroxisome proliferator-activated receptor α (PPARα). Furthermore, 25 μM GEN reduced the levels of phosphorylation of protein kinase B (Akt) and mechanistic target of rapamycin (mTOR). Moreover, most of these effects from GEN were reverted by pretreatment with the antagonist of ERβ. In conclusion, GEN improved hepatic lipid metabolism by activating ERβ and further modulation of Akt/mTOR signals. The results provide novel aspects of the regulatory mechanism of ERβ on hepatic lipid metabolism and might help to profoundly understand the functions of food-derived phytoestrogens in preventing and treating hepatic steatosis in postmenopausal women.


Associations of Habitual Mineral Intake with New-Onset Prediabetes/Diabetes after Acute Pancreatitis.
Associations between habitual dietary intake of minerals and glucose metabolism have been extensively studied in relation to metabolic disorders. However, similar research has yet to be conducted in individuals after acute pancreatitis (AP). The main aim was to investigate the associations between habitual intake of 13 minerals and glycaemic status: new-onset prediabetes/diabetes after AP (NODAP), pre-existing prediabetes/type 2 diabetes (T2DM), and normoglycaemia after AP (NAP). Associations between the dietary intake of minerals and markers of glucose metabolism (glycated haemoglobin and fasting plasma glucose) were also studied. The EPIC-Norfolk food frequency questionnaire was used in a cross-sectional fashion to determine the habitual intake of 13 dietary minerals. ANCOVA as well as multiple linear regression analyses were conducted and five statistical models were built to adjust for covariates. The study included 106 individuals after AP. In the NODAP group, intake of 4 minerals was significantly less when compared with the NAP group: iron (B = -0.076, p = 0.013), nitrogen (B = -0.066, p = 0.003), phosphorous (B = -0.046, p = 0.006), and zinc (B = -0.078, p = 0.001). Glycated haemoglobin was significantly associated with iodine intake (B = 17.763, p = 0.032) and manganese intake (B = -17.147, p = 0.003) in the NODAP group. Fasting plasma glucose was significantly associated with manganese intake (B = -2.436, p = 0.027) in the NODAP group. Habitual intake of minerals differs between individuals with NODAP, T2DM, and NAP. Prospective longitudinal studies and randomised controlled trials are now warranted to further investigate the associations between mineral intake and NODAP.


Reconfigurable multimode photonic-crystal waveguides.
We present the design and analysis of a novel reconfigurable photonic-crystal waveguide (PCW). The predefined waveguide is the result of the refractive-index variation of three rows of holes that can be obtained by the infiltration of liquids within what are otherwise air holes in a two-dimensional triangular-lattice photonic crystal. We compute the power transmission through the reconfigurable PCWs as well as through arbitrary waveguide bends. The advantages of writing reconfigurable PCW of a multimode nature are highlighted. We demonstrate the necessity to infiltrate high-refractive-index substances to obtain efficient power transfer via reconfigurable manner.


The role of trust in global health research collaborations.
Collaborations in global health research are on the rise because they enhance productivity, facilitate capacity building, accelerate output and make tackling big, multifactorial research questions possible. In this paper, I examine the concepts of trust and reliance in scientific collaborations in general, but also in the particular context of collaborations in global health research between high-income countries and low-and-middle income countries (LMIC). I propose and defend the argument that given the particular characteristics of collaborations and demands of trust relationships, reliance is a better relational mode for successful collaborations. Although reliance can be difficult to establish in situations where asymmetry of power exists, trust should not be the only relational mode available to LMIC researchers because of the type of vulnerability it introduces to the relationship. I conclude that the promotion of good collaborations requires addressing the power imbalances between partners, and establishing an even playing field in global health research.


Modulation of weight off-loading level over body-weight supported locomotion training.
With the evolution of robotic systems to facilitate overground walking rehabilitation, it is important to understand the effect of robotic-aided body-weight supported loading on lower limb muscle activity, if we are to optimize neuromotor recovery. To achieve this objective, we have collected and studied electromyography (EMG) data from key muscles in the lower extremity from healthy subjects walking over a wide range of body-weight off-loading levels as provided by a bespoke gait robot. By examining the impact of body-weight off-loading, it was found that muscle activation patterns were sensitive to the level of off-loading. In addition, a large off-loading might introduce disturbance of muscle activation pattern, led to a wider range of motion in terms of dorsiflexion/plantarflexion. Therefore, any future overground training machine should be enhanced to exclude unnecessary effect of body off-loading in securing the sustaining upright posture and providing assist-as-needed BWS over gait rehabilitation.


Who's who in Magelona: phylogenetic hypotheses under Magelonidae Cunningham & Ramage, 1888 (Annelida: Polychaeta).
Known as shovel head worms, members of Magelonidae comprise a group of polychaetes readily recognised by the uniquely shaped, dorso-ventrally flattened prostomium and paired ventro-laterally inserted papillated palps. The present study is the first published account of inferences of phylogenetic hypotheses within Magelonidae. Members of 72 species of Magelona and two species of Octomagelona were included, with outgroups including members of one species of Chaetopteridae and four of Spionidae. The phylogenetic inferences were performed to causally account for 176 characters distributed among 79 subjects, and produced 2,417,600 cladograms, each with 404 steps. A formal definition of Magelonidae is provided, represented by a composite phylogenetic hypothesis explaining seven synapomorphies: shovel-shaped prostomium, prostomial ridges, absence of nuchal organs, ventral insertion of palps and their papillation, presence of a burrowing organ, and unique body regionation. Octomagelona is synonymised with Magelona due to the latter being paraphyletic relative to the former. The consequence is that Magelonidae is monotypic, such that Magelona cannot be formally defined as associated with any phylogenetic hypotheses. As such, the latter name is an empirically empty placeholder, but because of the binomial name requirement mandated by the International Code of Zoological Nomenclature, the definition is identical to that of Magelonidae. Several key features for future descriptions are suggested: prostomial dimensions, presence/absence of prostomial horns, morphology of anterior lamellae, presence/absence of specialised chaetae, and lateral abdominal pouches. Additionally, great care must be taken to fully describe and illustrate all thoracic chaetigers in descriptions.


Studies of autistic traits in the general population are not studies of autism.
Studies of autistic traits in the general population are becoming increasingly prevalent. In this letter to the editor, we caution researchers against framing and interpreting studies of autistic traits in the general population as extending to autism and implore them to be clear about when their study sample does and does not include autistic participants.


[Stroke in young adults].
Stroke in young adults (15-45 years) is a rare condition. Up to 10% of patients with a first stroke admitted to the hospital belong in this age group. Stroke in the young patient is different from stroke in the elderly in several aspects such as etiology and prognosis. Usually, the management of stroke in young adults warrants an exhaustive etiological work-up. In this article, we review the most relevant issues in the study of young adults who suffer from stroke.


The effect of sleep on intracranial hemodynamics: a transcranial Doppler study.
The effect of sleep on intracranial blood flow velocities has not been reported in children or adults, even though blood flow velocities are evaluated for clinical purposes during both sleep and wakefulness. We report the effect of sleep on intracranial blood flow velocities of 11 healthy individuals (five children and six adults) who were monitored by polysomnography and transcranial Doppler sonography (TCD). Thirty-three TCDs were obtained on middle cerebral arteries. Before sleep, during non-rapid-eye-movement sleep, and after sleep, measurements of systolic, end diastolic, and mean flow velocities were obtained by TCD. Pulse oximetry and end tidal carbon dioxide were monitored during each 8-hour polysomnogram. The before-sleep blood flow velocity values were compared to sleep and after-sleep values in children and adults separately using ANOVA. A significant decrease in the blood flow velocities was noted during sleep compared to before-sleep values in both children (P less than .05) and adults (P less than .01). The blood flow velocities after sleep were also decreased compared to before-sleep values. This study shows that sleep reduces blood flow velocities in both children and adults. A decrease in blood flow velocities during normal sleep should be taken into account when interpreting TCDs in patients.


Functional analysis of four processing products from multiple precursors encoded by a lebocin-related gene from Manduca sexta.
Antimicrobial peptides (AMPs) are a crucial component of the natural immune system in insects. Five types of AMPs have been identified in the tobacco hornworm Manduca sexta, including attacin, cecropin, moricin, gloverin, and lebocin. Here we report the isolation of lebocin-related cDNA clones and antibacterial activity of their processed protein products. The 17 cDNA sequences are composed of a constant 5' end and a variable 3' region containing 3-16 copies of an 81-nucleotide repeat. The sequence of the corresponding gene isolated from a M. sexta genomic library and Southern blotting results indicated that the gene lacks introns and exists as a single copy in the genome. The genomic sequence contained 13 complete and one partial copy of the 81-nucleotide repeat. Northern blot analysis revealed multiple transcripts with major size differences. The mRNA level of M. sexta lebocin increased substantially in fat body after larvae had been injected with bacteria. The RXXR motifs in the protein sequences led us to postulate that the precursors are processed by an intracellular convertase to form four bioactive peptides. To test this hypothesis, we chemically synthesized the peptides and examined their antibacterial activity. Peptide 1 killed Gram-positive and Gram-negative bacteria. Peptide 2, similar in sequence to a Galleria mellonella AMP, did not affect the bacterial growth. Peptide 3 was inactive but peptide 3 with an extra Arg at the carboxyl terminus was active against Escherichia coli at a high minimum inhibitory concentration. Peptide 4, encoded by the 81-bp repeat, was inactive in the antibacterial tests. The hypothesis that posttranslational processing of the precursor proteins produces multiple bioactive peptides for defense purposes was validated by identification of peptides 1, 2, and 3 from larval hemolymph via liquid chromatography and tandem mass spectrometry. Comparison with the orthologs from other lepidopteran insects indicates that the same mechanism may be used to generate several functional products from a single precursor.


Unveiling mRNA changes during meiotic progression and pre-implantation development: help from large animal models.
Assisted reproductive technologies (ART) are successfully applied in several mammals, including humans, thanks to the ability of oocytes and embryos to face maturation, fertilization and first development in vitro. However, efficiency and safety of ART represent main issues. Mammalian oocytes and early embryos are transcriptionally inactive, and rely exclusively on maternal RNAs and proteins, deposited during oocyte growth, until embryonic genome activation (EGA). Such transcriptional quiescence needs complex post-transcriptional and post-translational mechanisms to coordinate meiotic maturation, fertilization, and reprogramming of the nascent genome. These events are the final outcome of complex, hormonally regulated biological processes that translate into specific molecular mechanisms, which are still far from being fully understood. A deep knowledge of these early phases of development is crucial to understand the core mechanisms of life onset, and to optimize the safety and efficiency of in vitro reproductive technologies. This work focuses on meiotic progression and pre-implantation development in mammals, underlining the importance of fundamental molecules stored during oocyte growth and selectively used during early embryogenic stages. Taking into account the species-specific behaviour of these pivotal molecules, this review describes the advantages of using large domestic animals for research in the reproductive field and proposes large domestic animals as models to improve human ART.


Bioassay-Guided Fractionation and In Vitro Antiproliferative Effects of Fractions of Artemisia nilagirica on THP-1 cell line.
ABSTACT Artemisia nilagirica (Clarke) is a widely used medicinal herb in Indian traditional system of medicine. Therefore, the present study was designed to evaluate the effects of A. nilagirica extracts/fractions on inhibition of proliferation and apoptosis in a human monocytic leukemia (THP-1) cell line. The crude extracts (A. nilagirica ethyl acetate extract [ANE] and A. nilagirica methanolic extract [ANA]) showed cytotoxic activity toward THP-1 cells with the IC50 values of 38.21 ± 7.37 and 132.41 ± 7.19 µg/ml, respectively. However, the cytotoxic activity of active fractions (ANE-B and ANM-9) obtained after column chromatography was found to be much more pronounced than their parent extracts. The IC50 values of ANE-B and ANM-9 were found to be 27.04 ± 2.54 µg/ml and 12.70 ± 4.79 µg/ml, respectively, suggesting greater susceptibility of the malignant cells. Cell cycle analysis and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) assay revealed that inhibition of cell growth by A. nilagirica fractions on THP-1 cells was mediated by apoptosis. Active fractions of A. nilagirica increased the expression levels of caspase-3, -7, and poly-ADP-ribose polymerase (PARP), a critical member of the apoptotic pathway. These results suggested that active fractions of A. nilagirica may play a promising role in growth suppression by inducing apoptosis in human monocytic leukemic cells via mitochondria-dependent and death receptor-dependent apoptotic pathways.


Primary lymphoma of the bladder treated successfully with mitozantrone gel.
We describe a young man who presented with a short history of painless haematuria. Subsequent investigations and biopsy of lesions found in his bladder at cystoscopy confirmed the diagnosis of primary lymphoma of the bladder. Computed tomography studies confirmed the disease was localised to his bladder. Unfortunately, the tumour was not eradicated by radiotherapy. However, it was successfully treated with intravesical mitozantrone given in a novel gel formation. Three years after diagnosis the patient remains well with no evidence of recurrence.


Safety and Tolerability of Fingolimod in Latin American Patients with Relapsing-Remitting Multiple Sclerosis: The Open-Label FIRST LATAM Study.
Fingolimod 0.5 mg is an orally active sphingosine 1-phosphate receptor modulator approved for use in adults with relapsing multiple sclerosis (MS). The efficacy and safety profile of fingolimod has been well characterized in a large clinical development program. Here, we report the safety and tolerability of fingolimod in relapsing-remitting MS (RRMS) patients from Latin America. A total of 162 patients with RRMS, predominantly from Latin American countries (138/162), were enrolled in this 16-week, single treatment arm, open-label, multi-center study. Unlike the phase III pivotal studies, this study permitted enrollment of patients with controlled diabetes, certain cardiac and pulmonary conditions, older age, and higher baseline Expanded Disability Status Scale. All patients were monitored clinically for a minimum of 6 hours after the first dose. Safety and tolerability assessments were based on adverse events, clinically notable laboratory abnormalities, vital signs, ophthalmic examinations, and electrocardiograms. Overall, the safety and tolerability profile was consistent with that reported previously in phase 3 studies and the FIRST study. Adverse events (AEs) were predominantly mild (n = 49, 35.5%) or moderate (n = 27, 19.6%). Three patients (2.2%) discontinued fingolimod due to AEs. Infections were reported in 33 patients (23.9%) and were predominantly mild in nature (n = 28, 20.3%). Increases in alanine aminotransferase enzymes of ≥3, ≥5 and ≥10 upper limit of normal were reported in five (3.7%), three (2.2%) and one (0.7%) patients, respectively. Hypertension cases (n = 3; 2.2%) did not result in treatment discontinuation and were controlled with antihypertensive therapy. Following first-dose administration, the majority of patients (90.6%) were discharged at 6 h. During the first-dose monitoring, 5 cases of bradycardia were reported; none required extended monitoring or treatment for symptomatic bradycardia. The first dose of fingolimod 0.5 mg was well tolerated in RRMS patients from Latin America. The overall safety profile was clinically manageable and consistent with previous fingolimod studies. Novartis. ClinicalTrials.gov #NCT01497262.


[Absence of effect of enalapril on the glycemic control and peripheral sensitivity to insulin in 10 diabetic patients treated with subcutaneous continuous infusion of insulin].
In diabetic patients, it has been suggested that angiotensin converting enzyme inhibitors may be associated with unexplained hypoglycaemic episodes. Such a side effect may limit the use of these drugs in diabetic hypertensive patients. Ten insulin-dependent diabetic patients mean age 38.4 +/- 13.1 years, mean diabetes duration 10.3 +/- 6.6 years (m +/- SD) were selected on the basis of good glycaemic control: HbA1: 7.6 +/- 0.9 per cent (upper limit of normal value less than 7.5 per cent) on continuous subcutaneous insulin infusion. In a double blind study, they were randomly and successively allocated for a 3 months period to enalapril 20 mg daily or placebo. Before treatment, after enalapril and placebo, mean blood glucose values, HbA1, daily insulin dosage were recorded as well as the number of clinical and biological (less than 3 mmol/l) hypoglycaemic episodes. Peripheral insulin sensitivity was assessed by euglycaemic insulin clamp technique. Compared to placebo, enalapril did not induce any modification of daily insulin dosage, glycaemic control. The incidence of hypoglycaemic episodes was similar. Neither peripheral insulin sensitivity was modified by enalapril. In the conditions of this study, enalapril did not interfere with glycaemic control in insulin-dependent diabetics in good metabolic control.


Review of emotion recognition in stroke patients.
Patients suffering from stroke have a diminished ability to recognize emotions. This paper presents a review of neuropsychological studies that investigated the basic emotion processing deficits involved in individuals with interhemispheric brain (right, left) damage and normal controls, including processing mode (perception) and communication channels (facial, prosodic-intonational, lexical-verbal). An electronic search was conducted using specific keywords for studies investigating emotion recognition in brain damage patients. The PubMed database was searched until March 2012 as well as citations and reference lists. 92 potential articles were identified. The findings showed that deficits in emotion perception were more frequently observed in individuals with right brain damage than those with left brain damage when processing facial, prosodic and lexical emotional stimuli. These findings suggest that the right hemisphere has a unique contribution in emotional processing and provide support for the right hemisphere emotion hypothesis. This robust deficit in emotion recognition has clinical significance. The extent of emotion recognition deficit in brain damage patients appears to be correlated with a variety of interpersonal difficulties such as complaints of frustration in social relations, feelings of social discomfort, desire to connect with others, feelings of social disconnection and use of controlling behaviors.


Non-convulsive Seizures Mimicking Creutzfeldt-Jakob Disease with Rapid Resolution and Recurrence of MRI Abnormalities.
An 88-year-old man presented with acute altered mental status. Brain magnetic resonance imaging (MRI) demonstrated "cortical ribboning," which is classically associated with Creutzfeldt-Jakob disease. His rapid clinical improvement prompted a follow-up MRI three days after presentation, which showed resolution of the acute abnormal signals. The patient was eventually diagnosed with non-convulsive seizure. Five months later, he returned with a similar clinical presentation and MRI findings after self-discontinuation of anticonvulsant. It is important for clinicians to be aware that neurological changes associated with non-convulsive seizures can acutely mimic Creutzfeldt-Jakob disease, and to consider a short interval follow-up MRI for diagnostic challenges in acute settings.


[Pulmonary sarcomatoid carcinoma: Clinical and prognostic characteristics, a case report].
Sarcomatoid carcinoma is a rare malignancy in the family of non-small-cell lung cancer. They belong to a mixed group of poorly differenciated neoplasia, including sarcomatous cells or sarcomatoid-like cells with giant or spindle cells. We report the case of a 69-year-old man with sarcomatoid carcinoma. We describe the main characteristics of these tumors. Diagnosis is frequently delayed and lesions are locally advanced. The prognostic is poorer than other non-small-cell lung cancer. Chemotherapy is often not efficient.


Impact of Physical Activity and Medication Adherence on the Seizure Frequency and Quality of Life of Epileptic Patients: A Population Study in West Texas.
Epilepsy is a neurological disease that affects 1-3% of the population. People with epilepsy (PWE) have poor physical and psychological health and a lower quality of life (QOL) than people without epilepsy. Moreover, PWE has more comorbid conditions (obesity, depression) than general populations. Physical activity (PA) has been reported to have various positive physical and psychological effects in PWE. Meanwhile, poor medication adherence is one of the main precipitating factors for seizure triggers. This study assessed the impact of PA and medication adherence on the seizure frequency and QOL for PWE at the Epilepsy Foundation, West Texas (EFWT). Our results indicate that PA is positively associated with the quality of life and negatively associated with the seizure frequency for PWE at EFWT, which suggests that physically active PWE tend to have fewer seizures and better QOL. Medication adherence did not affect the seizure frequency or QOL in our study. Yet, it is still crucial to encourage medication adherence for PWE since nonadherence is a known seizure promoter. Findings from this study highlight the continuous need to utilize available resources and implement programs to promote physical activity and medication adherence for better seizure control and QOL in PWE at EFWT.