Association between endothelin-1, nitric oxide, and Gensini score in chronic coronary syndrome.
Chronic coronary syndrome (CCS) is a major public health burden; its pathogenesis involves atherosclerosis and endothelial dysfunction. Endothelin-1 (ET-1) and nitric oxide (NO) are vasoactive substances synthesized by endothelial cells that play a crucial role in CCS development. The Gensini score (GS) is used for evaluating CCS severity based on lumen segment changes, stenosis degree, and coronary stenosis site. This prospective study included 71 patients with CCS; we evaluated the relationships between GS and ET-1 and NO serum levels were evaluated in these patients. The GS was calculated for all patients. Serum ET-1 & NO levels among other laboratory parameters were measured. The high GS group had higher ET-1 and relatively NO expressions in the than the low GS group. GS was positively correlated with ET-1 and negatively correlated with NO, T4, and TSH levels. The results of the multiple linear regression analysis showed that ET-1 had the most significant effect on GS. We found a strong association between ET-1, NO, and CCS severity. A combination of ET-1, NO, and GS is an essential predictor of CCS disease severity.


Deep Brain Stimulation as a Treatment for Refractory Epilepsy: Review of the Current State-of-the-Art.
Epilepsy affects ∼ 1% of the global population, and 33% of patients are nonresponsive to medication and must seek alternative treatment options. Alternative options such as surgery and ablation exist but are not appropriate treatment plans for some patients. Neurostimulation methods such as vagal nerve stimulation, responsive neural stimulation, and deep brain stimulation (DBS) are viable alternatives for medically refractory patients. DBS stimulation has been used in the treatment of Parkinson's disease, dystonia, and pain management. For the treatment of epilepsy, DBS has been found to be an effective treatment plan, with promising results of reduced seizure frequency and intensity. In this review, we discuss DBS surgery and equipment, mechanisms of DBS for epilepsy, and efficacy, technological specifications, and suggestions for future research. We also review a historical summary of experiments involving DBS for epilepsy. Our literature review suggests that further studies are warranted for medically refractory epilepsy using DBS.


The low affinity IgG receptor Fc gamma RIIB contributes to the binding of the mast cell specific antibody, mAb BGD6.
The mast cell specific monoclonal antibody, mAb BGD6, is a mast cell lineage marker [Jamur, M.C., Grodzki, A.C., Berenstein, E.H., Hamawy, M.M., Siraganian, R.P., Oliver, C., 2005. Identification and characterization of undifferentiated mast cells in mouse bone marrow. Blood 105, 4282-4289]. In rat basophilic leukemia (RBL-2H3) cells, mAb BGD6 precipitates cell-surface proteins of approximately 110 and 40-60 kDa. An expression cloning strategy was used to identify proteins that interact with mAb BGD6. A RBL-2H3 cDNA library in plasmids was transfected into PEAK cells, which do not bind mAb BGD6, and positive cells were selected with mAb BGD6. The plasmids recovered from the positive cells were amplified; retransfected into PEAK cells and after several screening cycles a positive clone was identified. This clone showed almost complete identity to Fc gamma RIIB (CD32), the low affinity IgG receptor. However, in contrast to the sequence in GenBank, this clone had an insert of 141 bp which codes for a longer isoform of this molecule with an extra 47 aa in its cytoplasmic domain. In RBL-2H3 cells both isoforms were expressed, with higher expression of the shorter form. The mechanism of binding of mAB BGD6 on both RBL-2H3 and CD32 transfected PEAK cells was then examined. Intact mAb BGD6 bound to both RBL-2H3 and CD32 expressing PEAK cells, but F(ab')(2) fragments bound only to RBL-2H3 cells demonstrating that mAb BGD6 binds to Fc gamma RIIB only through its Fc portion. On RBL-2H3 cells, the Fab of an anti-CD32 mAb partially inhibited the binding of intact mAb BGD6. The binding pattern of mAb BGD6 inhibited with anti-CD32 resembled that of the F(ab')(2) fragment of the antibody suggesting that the Fc portion of mAb BGD6 contributes to its binding on cells that have Fc gamma RIIB. These results are consistent with a model where mAb BGD6 binds through its Fab portion to a approximately 110 kDa protein and the Fc tail interacts with Fc gamma RIIB (CD32).


Epidemiology and prevention of meningococcal disease: a critical appraisal of vaccine policies.
Meningococcal disease is characterized by a marked variation in incidence and serogroup distribution by region and over time. In several European countries, Canada and Australia, immunization programs, including universal vaccination of infants or toddlers with catch-up campaigns in children and adolescents, aimed at controlling disease caused by meningococcal serogroup C have been successful in reducing disease incidence through direct and indirect protection. More recently, meningococcal conjugate vaccines targeting disease caused by serogroups A, C, W-135 and Y have been licensed and are being used in adolescent programs in the USA and Canada while a mass immunization campaign against serogroup A disease has been implemented in Africa. Positive results from clinical trials using vaccines against serogroup B disease in various age groups suggest the possibility of providing broader protection against serogroup B disease than is provided by the currently used outer membrane vesicle vaccines. The purpose of our review of meningococcal epidemiology and assessment of existing policies is to set the stage for future policy decisions. Vaccination policies to prevent meningococcal disease in different regions of the world should be based on quality information from enhanced surveillance systems.


A burst in the incidence of viral exanthems.
Vaccines have a major role in eradication programs of viral diseases. Vaccines against measles, rubella, and varicella are included in the vaccination schedules for children in most countries. A comparative analysis between 2011 and 2012 was performed to investigate if the number of patients with viral exanthemas reported to our clinic in 2012 was increased. PATIENTS WERE GROUPED IN FOUR CATEGORIES: rubella, measles, varicella and other viral exanthemas. Between January and April 2011, there were registered 37 cases with viral exanthemas: 69.5% presented with varicella and 30.5% with other viral exanthemas. Between January and April 2012, there were 178 cases registered with viral eruption, of which 37% were of other viral exanthemas, 35.4% rubella, 19.7% measles and 7.9% varicella. The highest incidence was seen in patients aged between 20 and 29 years (52.2%), with 21% having measles, 32.2% rubella, 9% varicella and 37.6% having other exanthemas. In 2012, the number of cases of viral exanthemas increased 5 times, with important outbreaks of new cases of measles and rubella. Although vaccines against measles and rubella were being used since 1979 and 1998 respectively, it was only in 2004, that these vaccines became part of the mandatory vaccination schedule. Although persons under 32 years should be protected against measles infection if they are previously vaccinated, more than 90% of the registered cases of measles occurred in such patients. The patients registered between January and April 2011 were mostly pediatric. Adults also were much more affected with measles, rubella, or varicella viruses in 2012 than in 2011.


Electrical stimulation for promoting peripheral nerve regeneration.
The peripheral nervous system has the intrinsic capacity to regenerate axons into target tissues, and peripheral nerves severely damaged or transected can be reconstructed by microsurgical techniques. The aim of peripheral nerve surgery is to pave way for fast and most possible thorough functional recovery. However, full functional recovery is rarely seen and several reasons for this have already been discovered. Based on these discoveries, therapeutic strategies supplementary to nerve microsurgery have been conceived with electrical stimulation of the denervated muscles or the proximal nerve stump or reconstructed area itself being among them. This chapter shortly describes the commonly accepted reasons for incomplete functional recovery and reviews the effects of varying electrical stimulation paradigms on the essentials for axonal regeneration and functional target reinnervation. We conclude the chapter with promising examples where electrical stimulation did already demonstrate to accelerate and increase functional recovery in the clinic.


Sparse cortical current density imaging in motor potentials induced by finger movement.
Predominant components in electro- or magneto-encephalography (EEG/MEG) are scalp projections of synchronized neuronal electrical activity distributed over cortical structures. Reconstruction of cortical sources underlying EEG/MEG can thus be achieved with the use of the cortical current density (CCD) model. We have developed a sparse electromagnetic source imaging method based on the CCD model, named as the variation-based cortical current density (VB-SCCD) algorithm, and have shown that it has much enhanced performance in reconstructing extended cortical sources in simulations (Ding 2009 Phys. Med. Biol. 54 2683-97). The present study aims to evaluate the performance of VB-SCCD, for the first time, using experimental data obtained from six participants. The results indicate that the VB-SCCD algorithm is able to successfully reveal spatially distributed cortical sources behind motor potentials induced by visually cued repetitive finger movements, and their dynamic patterns, with millisecond resolution. These findings of motor sources and cortical systems are supported by the physiological knowledge of motor control and evidence from various neuroimaging studies with similar experiments. Furthermore, our present results indicate the improvement of cortical source resolvability of VB-SCCD, as compared with two other classical algorithms. The proposed solver embedded in VB-SCCD is able to handle large-scale computational problems, which makes the use of high-density CCD models possible and, thus, reduces model misspecifications. The present results suggest that VB-SCCD provides high resolution source reconstruction capability and is a promising tool for studying complicated dynamic systems of brain activity for basic neuroscience and clinical neuropsychiatric research.


Ontological visualization of protein-protein interactions.
Cellular processes require the interaction of many proteins across several cellular compartments. Determining the collective network of such interactions is an important aspect of understanding the role and regulation of individual proteins. The Gene Ontology (GO) is used by model organism databases and other bioinformatics resources to provide functional annotation of proteins. The annotation process provides a mechanism to document the binding of one protein with another. We have constructed protein interaction networks for mouse proteins utilizing the information encoded in the GO annotations. The work reported here presents a methodology for integrating and visualizing information on protein-protein interactions. GO annotation at Mouse Genome Informatics (MGI) captures 1318 curated, documented interactions. These include 129 binary interactions and 125 interaction involving three or more gene products. Three networks involve over 30 partners, the largest involving 109 proteins. Several tools are available at MGI to visualize and analyze these data. Curators at the MGI database annotate protein-protein interaction data from experimental reports from the literature. Integration of these data with the other types of data curated at MGI places protein binding data into the larger context of mouse biology and facilitates the generation of new biological hypotheses based on physical interactions among gene products.


Proton pump inhibitors versus Cryptococcus species: effects on in vitro susceptibility and melanin production.
Aim: This study aimed to evaluate the effects of proton pump inhibitors (PPIs) on growth and melanin production by Cryptococcus spp. Materials & methods: Minimum inhibitory concentrations (MICs) of omeprazole, esomeprazole, rabeprazole, pantoprazole and lansoprazole against Cryptococcus spp. were determined and the effect of PPIs on melanin production was evaluated, in the presence or absence of copper sulfate or glutathione. Results: PPIs showed MICs ranging from 125-1000 μg/ml and decreased melanization by Cryptococcus cells. Addition of copper sulfate or gluthatione restored melanogenesis of cells grown in the presence of PPIs. The presence of PPIs and glyphosate decreased copper sulfate toxicity (1 mM). Conclusion: PPIs inhibited melanogenesis of Cryptococcus spp., possibly by chelating copper or inhibiting copper ATPase transport.


Clinical Gene Therapy for Neurodegenerative Diseases: Past, Present, and Future.
Clinical gene therapy has made important advances over the last decade. Among neurological diseases, severe genetic neurodegenerative conditions have been the focus of initial clinical applications. Gene therapy has also addressed complex neurodegenerative diseases, particularly Parkinson's disease, with encouraging results in human patients, demonstrating that specific targeting of central nervous system (CNS) cells is a relevant strategy for severe pathologies and that efficient access to the CNS with viral vectors is an achievable goal. The purpose of this review is to summarize the gene therapy clinical applications that have been conducted for neurodegenerative diseases. Limitations and hurdles to obtain and demonstrate benefit in patients, and the new developments that should allow new clinical applications with high beneficial potential are discussed.


Driving high-performance n- and p-type organic transistors with carbon nanotube/conjugated polymer composite electrodes patterned directly from solution.
We report patterned deposition of carbon nanotube/conjugated polymer composites from solution with high nanotube densities and excellent feature resolution. Such composites are suited for use as electrodes in high-performance transistors of pentacene and C(60), with bottom-contact mobilities of > 0.5 and > 1 cm(2) V(−1) s(−1), respectively. This represents a clear step towards development of inexpensive, high-performance all-organic circuits.


Sleep architecture and sleep-related mentation in securely and insecurely attached people.
Based on REM sleep's brain activation patterns and its participation in consolidation of emotional memories, we tested the hypothesis that measures of REM sleep architecture and REM sleep-related mentation would be associated with attachment orientation. After a habituation night in a sleep lab, a convenience sample of 64 healthy volunteers were awakened 10 minutes into a REM sleep episode and 10 minutes into a control NREM sleep episode in counterbalanced order, then asked to report a dream and to rate themselves and a significant other on a list of trait adjectives. Relative to participants classified as having secure attachment orientations, participants classified as anxious took less time to enter REM sleep and had a higher frequency of REM dreams with aggression and self-denigrating themes. There were no significant differences across attachment groups in other measures of sleep architecture or in post REM-sleep awakening ratings on PANAS subscales reflecting mood and alertness. Selected aspects of REM sleep architecture and mentation appeared to be associated with attachment orientation. We suggest that REM sleep plays a role in processing experiences and emotions related to attachment, and that certain features of sleep and dreaming reflect attachment orientations.


L-looped Transposition of the Great Arteries in a Patient with Marfanoid Habitus: First Reported Case in Literature.
L-looped transposition of great arteries (L-TGA) is an extremely rare heart condition. It is associated with physiologically corrected transposition of great vessels, leading to the normal return of deoxygenated systemic venous blood to the heart and transport of oxygenated pulmonary venous blood to the main systemic circulation. Anatomic discordancy and anomalous coronary artery distribution predispose the right ventricle to excessive workload and eventual heart failure. This mandates anatomic correction or proper medical management of heart failure. Herein, we present a case of a 14-year-old girl who presented to our cardiology consults with a false impression of pre-made clinical diagnosis of tetralogy of Fallot. She had increasing dyspnea and cyanosis on presentation. Striking marfanoid habitus and unusual echocardiographic findings of tripartite geometry of heart with parallel and discordant positioning of atria, ventricles, and great arteries led us to cardiac computed tomography which confirmed the diagnosis of L-TGA. Our patient also had associated patent ductus arteriosus, dextrocardia, ventricular septal defect (VSD), and pulmonary atresia. Due to the complex nature of heart disease and unavailability of resources, she was treated with a comprehensive heart failure protocol and followed up clinically and radiologically at regular intervals and showed massive improvement. This is the first-ever documented case of L-TGA with complex shunting and marfanoid habitus.


Arterial mapping with Duplex ultrasound: diagnostic-therapeutic strategy in patients with critical lower-limb ischemia.
Arteriography is the gold-standard in decision making in patients with critical lower-limb ischemia. Such method is not bereft of side effects and only gives morphologic information about lesions. Duplex allows to evaluate hemodynamically the arteriosclerotic lesions of ischemic lower limbs non-invasivelly and with the same reliability, in some studies, as angiography. Aim of this study was to determine the value and safety of arterial ultrasonic mapping in decision making for treatment of critical lower-limb ischemia. This was a prospective and comparative study in patients with critical lower-limb ischemia recruited from March 2005 to June 2006. Ultrasonic arterial mapping was performed in 130 patients. Arteriography was performed only in those patients with elevated risk of major amputation or if ultrasound was not feasible (44 patients). Patients were randomized into two groups according to decision making criteria: 1) group A based on mapping alone; 2) group B based on arteriography. There was no statistical difference between risk factors in the two groups (P>0.05). Cumulative patency was recorded and compared at one and three months (Log Rank) as well as degree of concordance of decision making using mapping and arteriography in the group with both tests (B); and degree of concordance of the two tests with decision making based on intraoperative findings. The degree of concordance between mapping and arteriography was 84.1% (P<0.0001), and the degree of concordance between mapping and arteriography with respect to final decision according to intraoperative findings was 93.1% and 97.7%, respectively (P<0.0001). There were no statistically significative differences in patency rates at one and three months between the two groups (P>0.05). Ultrasonic arterial mapping is sufficient and comparable to arteriography for purposes of decision making in patients with critical lower-limb ischemia.


Ataxic gait and mental retardation with absence of the paternal chromosome 8 and an idic(8)(p23.3): imprinting effect or nullisomy for distal 8p genes?
A female child with mild dysmorphisms, motor and mental retardation had a 45,XX,-8,-8,+psu dic(8)(p23.3) karyotype in blood lymphocytes, skin fibroblasts and in a lymphoblastoid cell line. DNA analysis showed that the proposita was nullisomic for the 8pter region distal to D8S264, at less than 1 cM from the telomere. Analysis of DNA polymorphisms of 38 loci spread along the entire chromosome 8 revealed that only maternal alleles were present, distributed in four heterozygous and four homozygous regions. This finding indicated that the rearrangement occurred during maternal meiosis in a chromosome recombinant with a minimum of seven crossovers. To our knowledge this is the first case of uniparental maternal disomy for chromosome 8 and of nullisomy for the distal 1-cM portion of the short arm. The available data are in favour of the assumption that no imprinted genes are present on chromosome 8. Thus, dysmorphisms, motor and mental retardation of the proposita are likely to be caused by the nullisomy for the region distal to D8S264, a region in which a recessive gene for epilepsy with progressive mental retardation is known to be located.


Adjuvant properties of a biocompatible thermo-responsive polymer of N-isopropylacrylamide in autoimmunity and arthritis.
To evaluate the thermo-responsive poly(N-isopropylacrylamide) (PNiPAAm) polymer as an adjuvant, we synthesized PNiPAAm through free radical polymerization and characterized it both in vitro and in vivo. The polymer when mixed with collagen type II (CII) induced antigen-specific autoimmunity and arthritis. Mice immunized with PNiPAAm-CII developed significant levels of CII-specific IgG response comprising major IgG subclasses. Antigen-specific cellular recall response was also enhanced in these mice, while negligible level of IFN-γ was detected in splenocyte cultures, in vitro. PNiPAAm-CII-immunized arthritic mouse paws showed massive infiltration of immune cells and extensive damage to cartilage and bone. As determined by immunostaining, most of the CII protein retained its native configuration after injecting it with PNiPAAm in naive mice. Physical adsorption of CII and the high-molecular-weight form of moderately hydrophobic PNiPAAm induced a significant anti-CII antibody response. Similar to CII, mice immunized with PNiPAAm and ovalbumin (PNiPAAm-Ova) induced significant anti-ovalbumin antibody response. Comparable levels of serum IFN-γ, IL-1β and IL-17 were observed in ovalbumin-immunized mice with complete Freund, incomplete Freund (CFA and IFA) or PNiPAAm adjuvants. However, serum IL-4 levels were significantly higher in PNiPAAm-Ova and CFA-Ova groups compared with the IFA-Ova group. Thus, we show for the first time, biocompatible and biodegradable thermo-responsive PNiPAAm can be used as an adjuvant in several immunological applications as well as in better understanding of the autoimmune responses against self-proteins.


MPYS, a novel membrane tetraspanner, is associated with major histocompatibility complex class II and mediates transduction of apoptotic signals.
Although the best-defined function of type II major histocompatibility complex (MHC-II) is presentation of antigenic peptides to T lymphocytes, these molecules can also transduce signals leading alternatively to cell activation or apoptotic death. MHC-II is a heterodimer of two transmembrane proteins, each containing a short cytoplasmic tail that is dispensable for transduction of death signals. This suggests the function of an undefined MHC-II-associated transducer in signaling the death response. Here we describe a novel plasma membrane tetraspanner (MPYS) that is associated with MHC-II and mediates its transduction of death signals. MPYS is unusual among tetraspanners in containing an extended C-terminal cytoplasmic tail (approximately 140 amino acids) with multiple embedded signaling motifs. MPYS is tyrosine phosphorylated upon MHC-II aggregation and associates with inositol lipid and tyrosine phosphatases. Finally, MHC class II-mediated cell death signaling requires MPYS-dependent activation of the extracellular signal-regulated kinase signaling pathway.


Anisotropy in haptic curvature and shape perception.
An investigation was undertaken into whether haptic comparison of curvature and of shape is influenced by the length/width ratio of the hand. For this purpose three experiments were conducted to test the curvature matching of curved strips (experiment 1), the curvature matching of cylindrically curved hand-sized surfaces (experiment 2), and the shape discrimination of elliptically curved hand-sized surfaces (experiment 3). The orientation of the stimuli with respect to the fingers was varied. The results of the two matching experiments showed that a given curvature is judged to be more curved when touched along the fingers than when touched across the fingers. The phenomenal flatness along and across the fingers was found to be different and subject dependent. The results of the shape-discrimination experiment showed that the orientation of ellipsoidal surfaces influences the judgments of the shapes of these surfaces. This influence could be predicted on the basis of results of the second matching experiment. It is concluded that similar mechanisms underlie the (anisotropic) perception of curvature and shape. For the major part the trends in the results can be explained by the length/width ratio of the hand and the phenomenal flatnesses.


The answer depends on the question: Optimal conditions for western blot characterization of muscle collagen type 1 depends on desired isoform.
Fibrillar collagen type 1 is the most abundant type of collagen within the body and is a critical component of extracellular infrastructure. In order to assess collagen synthesis and extracellular accumulation in fibrotic disorders, improved methods are needed to detect changes in procollagen versus mature collagen at the protein level. Using Western blot methodology, we systematically examined: (1) gel composition (Tris-glycine vs. bis-Tris, gradient vs. non-gradient, sodium dodecyl sulfate (SDS) vs. no SDS); (2) sample preparation (SDS vs. no SDS, β-mercaptoethanol (BME) vs. no BME, boiling vs. no boiling); and (3) running buffer composition (SDS vs. no SDS). Our results indicate full native gel conditions prevent resolution of all collagen type 1 bands. The best resolution of type 1 procollagens is achieved using 4%-12% Tris-glycine gels without the presence of SDS in the gel itself, although SDS in the running and sample buffers are needed. Also, BME must not be added to the sample buffer and samples should not be boiled. For characterization of mature collagen 1(I), both 8% and gradients type gels are appropriate, although still without SDS, yet with SDS included in both running and sample buffers, BME must be added to the sample buffer, and samples should not be boiled. Boiling is to be avoided as the antigenic site recognized by the monoclonal antibody used is sensitive to thermal denaturation, as is the case with many monoclonal antibodies available on the market. Thus, the exact parameters employed are dependent upon the collagen protein product that the scientist desires to identify.


Laparoscopic retroperitoneal heminephrectomy for renal cell carcinoma in horseshoe kidney: a case report and review of the literature.
In this case report, we demonstrate our technique of a retroperitoneal laparoscopic heminephrectomy for a T1b right hilar tumor in a horseshoe kidney. A 77-year-old Vietnamese woman presented to the hospital because of right flank pain. On presentation, her serum creatinine was 0.86 mg/dL and glomerular filtration rate was 65.2 mL/minute/1.73 m2. According to her renal scintigraphy, glomerular filtration rates of the right and left moieties were 24.2 and 35.5 mL/minute, respectively. Computed tomography imaging demonstrated a 5.5 × 5.0 cm solid hilar mass with a cT1bN0M0 tumor stage was in the right moiety. After discussion, the patient elected a minimally invasive surgery to treat her malignancy. The patient was placed in a flank position. We used Gaur's balloon technique to create the retroperitoneal working space, and four trocar ports were planned for operation. Three arteries were dissected, including two arteries feeding the right moiety, one artery feeding the isthmus, and one vein, which was clipped and divided by Hem-o-lok. The isthmusectomy was performed with an Endostapler. Consequently, the ureter was clipped and divided. Finally, the whole right segment of the horseshoe kidney was mobilized and taken out via the flank incision. The total operative time was 250 min with an estimated blood loss of 200 mL. The patient's serum creatinine after surgery was 1.08 mg/dL, and glomerular filtration rate was 49.47 mL/minute/1.73 m2. The patient was discharged on postoperative day #4 without complication. Final pathologic examination of the tumor specimen revealed a Fuhrman grade II clear cell renal cell carcinoma, capsular invasion, with negative surgical margins. After a three-month follow-up, the serum creatinine was 0.95 mg/dL, and glomerular filtration rate was 57.7 mL/minute/1.73 m2. Local recurrence or metastasis was not detected by follow-up computed tomography imaging. Retroperitoneal laparoscopic heminephrectomy is a safe and feasible technique for patients with renal cell carcinoma in a horseshoe kidney and may be particularly useful in low income settings without access to robotic technology.


In situ end labelling of DNA to detect apoptotic cell death in a variety of human tumours.
The present studies illustrate clinical applications of in situ end labelling (ISEL) of DNA to detect apoptosis in a variety of human malignancies including myelodysplastic syndromes (MDS, n=10), non-Hodgkin's lymphoma (NHL, n=10), head and neck cancer (n = 3), breast cancer (n = 1) and cervical cancer (n = 1). These studies also describe a new in situ double labelling technique to detect apoptosis and proliferation (S-phase cells) simultaneously in the same section of plastic embedded tissue. In vivo intravenous infusions of thymidine analogues (i.e. bromodeoxyuridine (BrdU) and/or iododeoxyuridine (IUdR)) followed by their detection with a specific monoclonal antibody in a plastic embedded biopsy, combined with ISEL in the same section, facilitated simultaneous estimations of apoptosis and proliferation. The most salient finding of these studies was excessive apoptosis in MDS including the cells in S-phase as indicated by uniquely double labelled cells in their bone marrow biopsies. On the other hand, a very low degree of apoptosis was observed in NHL and other solid tumours. Moreover, the solid tumours exhibited definite compartments of apoptosis and proliferation. Further experiments are underway to confirm these findings in a larger study in order to design appropriate therapeutic modalities for these disorders.


Course of size and density of metastatic renal cell carcinoma lesions in the early follow-up of molecular targeted therapy.
Imaging-based monitoring of molecular therapies in oncology remains a challenge. Molecular therapies might have more pronounced effects on lesion density than on lesion size. We analyzed changes in lesion diameter and density in patients with metastasized renal cell cancer (mRCC) in the early follow-up of targeted therapy and compared size-based measurements according to Response Evaluation Criteria in Solid Tumors (RECIST) with size- and density-based response evaluations according to the Choi criteria. A total of 22 patients treated with sorafenib (800 mg/d) were retrospectively analyzed. Relative changes (in %) in the greatest diameter and density of defined neoplastic "target lesions" were determined 8 weeks and 1 year after start of therapy in relation to a pretherapeutic baseline investigation. Data were analyzed according to RECIST (ver. 1.0), and results were compared with the response assessment based on Choi. Median survival was determined for all subgroups according to Choi or RECIST at the 8-week and 1-year follow-up. Applying RECIST, 18 patients (82%) demonstrated stable disease (SD) 8 weeks after the start of targeted therapy, 3 patients (14%) partial response (PR), and 1 patient (4%) progressive disease (PD). Partial responders at 8 weeks had a median survival of 48 months. After 1 year, 59% of all patients still showed SD. Applying Choi, 15 patients (68%) showed PR 8 weeks after the start of therapy, 5 patients (23%) SD, and 2 patients (9%) PD. After 1 year, PR was still the predominant response group (64% of the patients). Partial responders after 8 weeks had a median survival of 18 months. Choi defined more patients as partial responders at early stages of therapy than RECIST, but this was not an effective selection for patients with prolonged median survival. Evaluation of a larger patient cohort will further clarify the role of combined size- and density-based follow-up strategies in targeted therapy of mRCC.


Interplay of wavelength, fluence and spot-size in free-electron laser ablation of cornea.
Infrared free-electron lasers ablate tissue with high efficiency and low collateral damage when tuned to the 6-microm range. This wavelength-dependence has been hypothesized to arise from a multi-step process following differential absorption by tissue water and proteins. Here, we test this hypothesis at wavelengths for which cornea has matching overall absorption, but drastically different differential absorption. We measure etch depth, collateral damage and plume images and find that the hypothesis is not confirmed. We do find larger etch depths for larger spot sizes--an effect that can lead to an apparent wavelength dependence. Plume imaging at several wavelengths and spot sizes suggests that this effect is due to increased post-pulse ablation at larger spots.


[Design and implementation of a multicenter case-control study on bladder cancer in Spain].
The aim of a case-control design is to make a measurement of the highest possible accuracy, reducing to a minimum the possible selection, information and confusion biases. The design, methods and procedures of a multicentric study carried out in 14 hospitals from 4 autonomous communities in Spain are discussed. Overall 254 incident cases, 243 prevalent cases, 583 hospital controls and 530 population controls were included. The proportion of nonresponders was somewhat higher in population controls, particularly in large cities. Statistically significant differences between cases and controls were not found for socioeconomic levels, educational level, number of jobs, degree of response, duration of the interview, and errors of transcription and codification of information. Also, significant differences were not found between the population and hospital controls regarding diet habits and cigarette smoking. It is considered that a non-biased measurement of the association can be obtained from cases and hospital controls. The collected information was satisfactory. In spite of the lack of adequate facilities for research in hospitals, the development of multicentric etiologic studies is feasible.


Effects of inorganic arsenic on the rat and mouse urinary bladder.
Inorganic arsenic (arsenate and arsenite) is a known human carcinogen, inducing tumors of the skin, urinary bladder, and lung. Understanding the mechanism of inorganic arsenic carcinogenesis has been hampered by a lack of animal models. To define the urothelial effects of inorganic arsenic, we administered arsenate and arsenite in the diet or drinking water to rats and mice in several short-term experiments (2-10 weeks). Treatment with arsenate or arsenite in the drinking water or diet induced cytotoxicity and necrosis of the urothelial superficial layer and hyperplasia in rats and mice. Arsenate-induced changes occurred later in mice compared with arsenite-induced changes, but not in the rat. Hyperplasia in rats was evident by light microscopy at an earlier time point (2 weeks) than previously observed after treatment with dimethylarsinic acid (DMA(V)). The bromodeoxyuridine labeling index was increased in treated rats. We were unable to determine the bromodeoxyuridine labeling index in mice. The effects of inorganic arsenicals on the bladder were greater when administered in the drinking water than in the diet in rats and mice, but so was the overall toxicity to the animal. The female rat appeared more sensitive to the effects of inorganic arsenic than the male rat, but effects were similar in female and male mice. The mode of action of inorganic arsenic in rats and mice appears to involve urothelial cytotoxicity, increased cell proliferation and ultimately tumors. Cytotoxicity is likely due to the generation of reactive trivalent arsenicals excreted in the urine.


Achieving High Reliability with People, Processes, and Technology.
High reliability as a corporate value in healthcare can be achieved by meeting the "Quadruple Aim" of improving population health, reducing per capita costs, enhancing the patient experience, and improving provider wellness. This drive starts with the board of trustees, CEO, and other senior leaders who ingrain high reliability throughout the organization. At WellStar Health System, the board developed an ambitious goal to become a top-decile health system in safety and quality metrics. To achieve this goal, WellStar has embarked on a journey toward high reliability and has committed to Lean management practices consistent with the Institute for Healthcare Improvement's definition of a high-reliability organization (HRO): one that is committed to the prevention of failure, early identification and mitigation of failure, and redesign of processes based on identifiable failures. In the end, a successful HRO can provide safe, effective, patient- and family-centered, timely, efficient, and equitable care through a convergence of people, processes, and technology.


Cross-sectional study of the association between empathy and burnout and drug prescribing quality in primary care.
The aim of this study was to assess whether burnout and empathy levels among general practitioners (GPs) might influence prescribing performance assessed using pharmaceutical prescription quality standard indicators. Cross-sectional descriptive study of 108 GPs from 22 primary care centers in Lleida, Spain, and of centralized data corresponding to 183 600 patients under their care. The study was conducted between May and July 2014. Burnout and empathy were measured using the Spanish versions of the Maslach Burnout Inventory and the Jefferson Scale for Physician Empathy, and prescribing quality was measured using the Catalan Pharmaceutical Prescription Quality Standard (EQPF). Normal distribution of scores was verified using the Chi-square and Kolmogorov-Smirnov-Lilliefors tests. The effect of each of the variables was evaluated using crude odds ratios. Older GPs scored significantly higher in the EQPF (P < 0.05). High empathy scores were positively associated with high EQPF scores. GPs with low burnout also performed better in the EQPF. More empathic, less burned-out, older GPs showed better prescribing performance according to quality indicators. However, further studies are needed to evaluate other factors influencing prescribing habits. The promotion of communication skills may increase empathy and reduce burnout, thus benefiting patients.


Identification and characterization of variant alleles of human acetyltransferase NAT1 with defective function using p-aminosalicylate as an in-vivo and in-vitro probe.
Although several variant alleles at the human NAT1 gene locus have been reported, their relationship to phenotypic variations in NAT1 function remains unclear. We have used in-vivo and invitro phenotyping tests, along with PCR-based cloning and heterologous expression, to investigate the extent of variation in NAT1 function and to characterize novel allelic variants at the NAT1 gene locus. The NAT1-selective substrate p-aminosalicylic acid (PAS) was used as a probe for NAT1 function. In-vivo PAS acetylation rates were estimated by determining the ratio of PAS to N-acetylated PAS (AcPAS) in urine and plasma following the oral ingestion of Nemasol Sodium. Excluding outliers, a 65-fold variation in the urinary AcPAS:PAS ratio was observed (n = 144), while a 5.6-fold variation in the plasma AcPAS:PAS ratio was seen in a subset (n = 19) of this sample. Urinary and plasma ratios correlated moderately (r = 0.74, p < 0.0005). One individual (case 244) had a marked impairment of PAS N-acetylation, with 10-fold lower urinary and plasma AcPAS:PAS ratios compared with other subjects. Biochemical investigations in whole blood lysates from case 244 suggested a NAT1 kinetic defect, with a 20-fold increased apparent K(m) for PAS and a 90-fold decreased Vmax for AcPAS formation. We subcloned, sequenced and expressed the protein-coding regions of the NAT1 alleles from case 244 and from seven other selected probands. Sequence analysis revealed the presence of two new variant alleles, designated as NAT1 x 14 and NAT1 x 15, in case 244, as well as one variant, NAT1 x 11, which has been observed in previous investigations. NAT1 x 14 contained a missense mutation (G560-->A) that is predicted to change a single amino acid (Arg187-->Gln), as well as two 3' non-coding region mutations (T1088-->A and C1095-->A) that have previously been observed in the NAT1 x 10 allelic variant. NAT1 x 15 had a single nonsense mutation (C559-->T; Arg187-->stop) and, thus, encodes a truncated protein. The activity of recombinant NAT1 14 mirrored the defective enzyme function in whole blood lysates from case 244, while NAT1 15 was completely inactive. Expressed NAT1 11, on the other hand, had identical activity to the wild type NAT1 4 allele, suggesting that the coding region mutations in this variant are functionally silent. The frequencies of NAT1 x 11, NAT1 x 14 and NAT1 x 15 were 0.021, 0.028 and 0.014 (n = 288 alleles), respectively, suggesting that they are relatively rare in our predominantly Caucasian sample.


Good guy or bad guy: the opposing roles of microRNA 125b in cancer.
MicroRNAs (miRNAs) are a class of non-coding RNAs that post-transcriptionally silence target mRNAs. Dysregulation of miRNAs is a frequent event in several diseases, including cancer. One miRNA that has gained special interest in the field of cancer research is miRNA-125b (miR-125b). MiR-125b is a ubiquitously expressed miRNA that is aberrantly expressed in a great variety of tumors. In some tumor types, e.g. colon cancer and hematopoietic tumors, miR-125b is upregulated and displays oncogenic potential, as it induces cell growth and proliferation, while blocking the apoptotic machinery. In contrast, in other tumor entities, e.g. mammary tumors and hepatocellular carcinoma, miR-125b is heavily downregulated. This downregulation is accompanied by de-repression of cellular proliferation and anti-apoptotic programs, contributing to malignant transformation. The reasons for these opposing roles are poorly understood. We summarize the current knowledge of miR-125b and its relevant targets in different tumor types and offer several hypotheses for the opposing roles of miR-125b: miR-125b targets multiple mRNAs, which have diverse functions in individual tissues. These target mRNAs are tissue and tumor specifically expressed, suggesting that misregulation by miR-125b depends on the levels of target gene expression. Moreover, we provide several examples that miR-125b upregulation dictates oncogenic characteristics, while downregulation of miR-125b corresponds to the loss of tumor suppressive functions. Thus, in different tumor entities increased or decreased miR-125b expression may contribute to carcinogenesis.


Predicting skeletal muscle mass from dual-energy X-ray absorptiometry in Japanese prepubertal children.
We aimed to develop regression-based prediction equations for estimating total and regional skeletal muscle mass (SMM) from measurements of lean soft tissue mass (LSTM) using dual-energy X-ray absorptiometry (DXA) and investigate the validity of these equations. In total, 144 healthy Japanese prepubertal children aged 6-12 years were divided into 2 groups: the model development group (62 boys and 38 girls) and the validation group (26 boys and 18 girls). Contiguous MRI images with a 1-cm slice thickness were obtained from the first cervical vertebra to the ankle joints as reference data. The SMM was calculated from the summation of the digitized cross-sectional areas. Total and regional LSTM was measured using DXA. Strong significant correlations were observed between the site-matched SMM (total, arms, trunk and legs) measured by MRI and the LSTM obtained by DXA in the model development group for both boys and girls (R2adj=0.86-0.97, P<0.01, standard error of the estimate (SEE)=0.08-0.44 kg). When these SMM prediction equations were applied to the validation group, the measured total (boys 9.47±2.21 kg; girls 8.18±2.62 kg) and regional SMM were very similar to the predicted values for both boys (total SMM 9.40±2.39 kg) and girls (total SMM 8.17±2.57 kg). The results of the Bland-Altman analysis for the validation group did not indicate any bias for either boys or girls with the exception of the arm region for the girls. These results suggest that the DXA-derived prediction equations are precise and accurate for the estimation of total and regional SMM in Japanese prepubertal boys and girls.


Feasibility of Valve-in-Valve Procedure for Degenerated St. Jude Medical Trifecta Bioprosthesis.
The valve-in-valve (ViV) procedure is an option for patients with symptomatic structural degeneration of a bioprosthesis and excessive reoperative risk. The risk of coronary obstruction appears to be increased if ViV is performed for certain pericardial prostheses in which the leaflets are mounted outside the stent posts. Herein is described a successful ViV for a degenerated Trifecta aortic bioprosthesis, and the technical considerations for performing a ViV procedure within such types of prosthesis are considered. Emphasis is placed on the importance of preoperative investigations (computed tomography scan-based measurements of coronary ostial height and of sinus of Valsalva diameters), and on the precise deployment of the valve (transapical approach with transesophageal echocardiography control) to minimize the risk of major complications. The presence of a failing Trifecta bioprosthesis should not be considered an absolute contraindication to ViV on the basis of the risk of coronary obstruction.


Circadian Profiling of Amino Acids in the SCN and Cerebral Cortex by Laser Capture Microdissection-Mass Spectrometry.
The suprachiasmatic nucleus (SCN) is an extremely robust self-sustained oscillator, containing virtually the same molecular clock present in other tissues in the body but, in addition, endowed with tight intercellular coupling dependent on multiple neurotransmitter systems that allow the SCN to function as the "master clock." Several studies on the circadian SCN transcriptome have been published and compared with the transcriptome of other tissues, but the recent focus shift toward the circadian metabolome and the importance of small molecules for circadian timekeeping has so far been limited to macroscopic tissues such as the liver. Here, we report the successful use of laser capture microdissection coupled with liquid chromatography/tandem mass spectrometry for the circadian profiling of SCN amino acids. Among 18 amino acids detected, 10 (55.5%) showed significant variations, particularly marked for proline, lysine, and histidine, with higher levels during the subjective day. Moreover, we compared SCN and cortical amino acid levels between wild-type and Bmal1-deficient animals, either in the whole body or specifically in the liver. Interestingly, lack of Bmal1 in the whole body led to a significant increase in most amino acids in the SCN but not in the cerebral cortex. In contrast, deletion of Bmal1 in the liver mostly affected cortical amino acid levels during the subjective day. This study demonstrates that laser capture microdissection can be used for the isolation of microscopic brain structures for metabolomic purposes and reveals interactions between liver and SCN amino acid metabolism.


Acupuncture and in vitro fertilization: a retrospective chart review.
In 2007, Craig et al. reported the results of a randomized controlled trial in which a standardized acupuncture protocol performed on the day of embryo transfer (ET) resulted in lower pregnancy rates after in vitro fertilization (IVF). Between 2005 and 2007, the Craig protocol was used by one of the authors (LHR) at an infertility clinic unaffiliated with the Craig et al. trial. The objective was to retrospectively review clinic records to evaluate the effect of the Craig protocol in both donor and nondonor IVF cycles on four outcomes: (1) live births; (2) biochemical pregnancies; (3) adverse outcomes; and (4) live births in nondonor cycles across age groups established by the Society for Assisted Reproductive Technology. The study design was a retrospective chart review. The study was conducted at a private infertility clinic. Patients underwent fresh, donor (N=70) or nondonor (N=402) IVF-ET. The Craig protocol included the following points before ET: GV-20, CV-6, ST-29, SP-8, PC-6, LV-3; Shenmen and Brain on the left ear; and Uterus and Endocrine on the right ear. After transfer the points were LI-4, SP-10, ST-36, SP-6, KI-3; Uterus and Endocrine on the left ear; and Shenmen and Brain on the right ear. Live births (LB) beyond 24 weeks' gestation was the main outcome measure. In nondonor IVF cycles, there were no differences in LB across age groups (odds ratio [OR]=1.04, 95% confidence interval [CI] 0.68-1.57), biochemical pregnancies (OR=0.60, 95% CI 0.27-1.33), or adverse outcomes (OR=0.63, 95% CI 0.31-1.26). In donor cycles, LB were higher in the acupuncture group (relative risk=1.31, 95% CI 1.02-1.71). In this observational study, the Craig protocol was not found to lower IVF LB. In fact, the Craig protocol was associated with higher LB in donor cycles. These findings should be considered cautiously because more adequately powered, randomized research is needed.


Effect of colored lenses on muscular performance.
The effect of color on physiological parameters appears well documented. However, methodological weaknesses and limitations to practical application suggest it to be substantially under researched with regard to physical performance. The aim of this study was to consider the effects of red, blue and clear (control) colored lens glasses on a muscular endurance task. Fifteen healthy males (21±1.34 years) were instructed to perform repetitions to failure using their predetermined 25 repetition maximum (RM) on a seated leg press. Participants completed three randomised trials exposed to blue, red and clear lenses. A repeated measure ANOVA identified a significant difference in the amount of repetitions performed between the three conditions. A pairwise comparison revealed significantly greater repetitions for the blue lens condition compared to clear lenses (P=0.008). From the data an effect size (ES) of 0.76 was calculated for blue lensed glasses. The red lens condition showed no significant variation from clear lenses in repetitions performed. The findings of this research suggest that exposure to the color blue improves performance of a muscular endurance based task. Such a simple and inexpensive performance enhancement warrants further investigation to explore different exercise modalities as well as effects of different colored lenses, and the mechanisms as to how color affects performance.


Sputum cysteinyl leukotrienes increase 24 hours after allergen inhalation in atopic asthmatics.
We have used the relatively noninvasive technique of induced sputum to measure allergen-induced changes in the concentration of eicosanoid mediators in bronchial secretions from atopic asthmatics. Sputum induction was performed before and 24 h after inhalational allergen challenge in 14 atopic asthmatics who developed a late asthmatic reaction (LAR). Differential cell counts were made on sputum cytospins and eicosanoid (cysteinyl leukotrienes [cys LTs], prostaglandin D(2) [PGD(2)], and PGE(2)) concentrations were measured in the sputum supernatants. The percentage of eosinophils at baseline correlated with the concentration of cys LTs (r = 0.84, p < 0.001) but not prostanoid mediators. Allergen challenge produced a significant increase in the concentration of sputum cys LTs from 3. 45 ng/ml sputum to 11.95 ng/ml (p = 0.002), which correlated with the increase in sputum eosinophils (r = 0.55, p < 0.05). There were no significant changes in PGD(2) or PGE(2) concentrations in sputum supernatants in response to challenge. Thus, the noninvasive technique of induced sputum has been used to demonstrate increased cys LTs, but not prostanoids associated with LAR after allergen challenge. The correlation between eosinophil numbers and cys LT concentrations at baseline values and 24 h after allergen challenge is consistent with these cells being a principal source of cys LTs within the airways at these time points.


Genetic counseling students' use of patient-centered communication skills predicts standardized patient satisfaction during virtual simulated sessions.
Communication is essential to effective genetic counseling, but few studies have systematically evaluated methods of assessing communication skills among genetic counseling trainees. The study's objective is to compare the strength of associations between standardized patient (SP) satisfaction with simulated genetic counseling sessions and student skill use during the sessions, as reported by SPs and students. We hypothesized that (1) Both SP- and student-reported skill use will be significantly associated with SP satisfaction ratings during the baseline simulation and (2): SP ratings of student skill use will show a stronger relationship to SP satisfaction than student self-rating of skill use. Sixty genetic counseling students and recent graduates (referred to as "students") from accredited U.S. and Canadian programs participated in the study and completed a baseline virtual-simulated genetic counseling session. Both students and SPs completed post-session questionnaires about communication skill use (a 22-item checklist) and SPs completed a satisfaction questionnaire based on the session (a 14-item Likert scale). Multilevel regression models assessed associations between SP satisfaction during the baseline session and SP- or student-reported skill use. SP satisfaction was significantly associated with skill use reported by both SPs and students, but the model based on SP report explained a higher proportion of the variance in SP satisfaction than student-reported skill use (SP model fixed effects R2 = 27%, adjusted R2 = 21%; vs. student model R2 = 7%, adjusted R2 = -2%). For both the SP and student models, use of more skills from the LISTEN domain (which focused on eliciting the patient's perspective) was associated with higher SP satisfaction, while other skill category domains were not. These findings support the SP satisfaction measure as sensitive to variation in student performance of key communication skills, especially those eliciting the patient's perspective. Moreover, SP assessment of session satisfaction can be a useful assessment of student communication performance and a meaningful proxy for actual patient satisfaction.


Fulminant course in a case of diffuse myelinoclastic encephalitis-- a case report.
We report on a 10-year old previously healthy boy who exhibited a fulminant and nearly monophasic clinical course of demyelinating encephalitis with relapsing intracranial hypertension syndrome. Histologic examination of a diagnostic brain biopsy revealed an inflammatory demyelinating process with perivascular T lymphocytic infiltration and axonal damage reminiscent of multiple sclerosis-like lesions. In the brain, the DNA of human Herpes virus 6 (HHV6) was detectable. Eleven months after the initial symptoms and on maintainance with oral steroids, MRI showed demyelination of both hemispheres as well as demyelination of the brain stem and Wallerian degeneration. The boy exhibited a severe neurologic defect syndrome. The clinical and radiological course is unusual because of the asymmetric progression of the encephalitis and the extensive confluent lesions without demarcated border or enhancement of the rim after injection of gadolinium. The clinical course showed no definite steroid response. The pathogenetic relevance of HHV6 remains elusive. Although single patients with HHV6-associated encephalomyelitis have been reported, HHV6 DNA is occasionally detected in brains of healthy individuals.


Alpine cushion plants inhibit the loss of phylogenetic diversity in severe environments.
Biotic interactions can shape phylogenetic community structure (PCS). However, we do not know how the asymmetric effects of foundation species on communities extend to effects on PCS. We assessed PCS of alpine plant communities around the world, both within cushion plant foundation species and adjacent open ground, and compared the effects of foundation species and climate on alpha (within-microsite), beta (between open and cushion) and gamma (open and cushion combined) PCS. In the open, alpha PCS shifted from highly related to distantly related with increasing potential productivity. However, we found no relationship between gamma PCS and climate, due to divergence in phylogenetic composition between cushion and open sub-communities in severe environments, as demonstrated by increasing phylo-beta diversity. Thus, foundation species functioned as micro-refugia by facilitating less stress-tolerant lineages in severe environments, erasing a global productivity - phylogenetic diversity relationship that would go undetected without accounting for this important biotic interaction.


Immunological properties of monoclonal antibodies specific for meningococcal polysaccharides: the protective capacity of IgM antibodies specific for polysaccharide group B.
Two IgM monoclonal antibodies, MB32 and MB34 specific for meningococcal polysaccharide group B have been raised. Both were detectable by radioimmunoassay and agglutination, but only MB34 was effective in counter immunoelectrophoresis and complement fixation. MB34 was also far more potent than MB32 when tested for passive protection of mice infected with either Neisseria meningitidis group B or Escherichia coli K1. These data demonstrate that group B-specific antibodies do play a protective role in mice infected with these bacteria.


[Electric cardioversion in the emergency service. Experience in 1000 cases].
We describe our experience with 1000 electric cardioversions performed at the emergency ward in the Hospital of Cardiology y Neumology, National Medical Center I.M.S.S. The objectives are: 1. Report our experience. 2. Investigate if digitalis treatment should be discontinued before the procedure. 3. Determine if all patients should be on anticoagulant therapy for elective cardioversion. 4. Indicate the optimal anesthetic drug with minimal side effects. A therapeutic procedure was performed in 73% of our cases and an elective one in the remaining 27%. Patients were grouped as ischemic heart disease 26%, rheumatic heart disease 24%, chronic obstructive pulmonary disease 14%, systemic hypertensive heart disease 13%, without clinical heart disease 6%, preexcitation syndrome 6%, adult congenital heart disease 4%, with implanted pacemaker 2%, pregnancy 2% and diverse myocardial diseases 2%. As a cardiac arrhythmias atrial fibrillation was the main cause 45%. Atrial flutter represented 25%, atrial paroxysmal tachycardia was 21% and ventricular tachycardia 9%. A cardioversion was performed in 43% of patients under digitalis treatment at therapeutic levels, without complications. Atrial flutter reverted to sinus rhythm in 98% of the procedures, and atrial fibrillation in 97%. Elective cardioversion in patients with atrial fibrillation was achieved with energies of 200 joules in 82% of the procedures (P less than 0.001) and in atrial flutter with 100 joules in 89% of the cases (P less than 0.001). The most frequent complications were atrial and junctional premature beats in 41% of the cases. We consider this procedure a safe one, effective at the energy levels described, with no need for discontinuation of digitalis therapy, with no mandatory previous anticoagulant therapy, and with no contraindications on pregnancy or implanted pacemakers.


Hypoglycemia detected during cardiac arrest of a non-diabetic patient with heart failure.
Hypoglycemia in non-diabetic patients with heart failure is a rare finding. It is thought to be caused by hepatic dysfunction secondary to chronic passive congestion, and reduced gluconeogenesis. In this report we present a 23-year-old man with a history of Duchenne muscular dystrophy hospitalized for decompensated heart failure and implantable cardioverter defibrillator shock. Laboratory examination on admission showed slightly elevated levels of hepatic enzymes. Despite the therapy for heart failure the patient's clinical status deteriorated, and sinus bradycardia and then cardiac arrest occured. After successful 5-minute cardiopulmonary resuscitation, an arterial blood sample revealed metabolic acidosis with a level of pH 7.04, bicarbonate 9.3, and glucose of 22 mg/dl. Acute treatment of metabolic acidosis with hypoglycemia was successfully performed. Based on this case, possible causes of unexplained hypoglycemia in non-diabetic patients with heart failure were described in a short literature review.


Different activation signals induce distinct mast cell degranulation strategies.
Mast cells (MCs) influence intercellular communication during inflammation by secreting cytoplasmic granules that contain diverse mediators. Here, we have demonstrated that MCs decode different activation stimuli into spatially and temporally distinct patterns of granule secretion. Certain signals, including substance P, the complement anaphylatoxins C3a and C5a, and endothelin 1, induced human MCs rapidly to secrete small and relatively spherical granule structures, a pattern consistent with the secretion of individual granules. Conversely, activating MCs with anti-IgE increased the time partition between signaling and secretion, which was associated with a period of sustained elevation of intracellular calcium and formation of larger and more heterogeneously shaped granule structures that underwent prolonged exteriorization. Pharmacological inhibition of IKK-β during IgE-dependent stimulation strongly reduced the time partition between signaling and secretion, inhibited SNAP23/STX4 complex formation, and switched the degranulation pattern into one that resembled degranulation induced by substance P. IgE-dependent and substance P-dependent activation in vivo also induced different patterns of mouse MC degranulation that were associated with distinct local and systemic pathophysiological responses. These findings show that cytoplasmic granule secretion from MCs that occurs in response to different activating stimuli can exhibit distinct dynamics and features that are associated with distinct patterns of MC-dependent inflammation.


Role of recent and old riverine barriers in fine-scale population genetic structure of Geoffroy's tamarin (Saguinus geoffroyi) in the Panama Canal watershed.
The role of physical barriers in promoting population divergence and genetic structuring is well known. While it is well established that animals can show genetic structuring at small spatial scales, less well-resolved is how the timing of the appearance of barriers affects population structure. This study uses the Panama Canal watershed as a test of the effects of old and recent riverine barriers in creating population structure in Saguinus geoffroyi, a small cooperatively breeding Neotropical primate. Mitochondrial sequences and microsatellite genotypes from three sampling localities revealed genetic structure across the Chagres River and the Panama Canal, suggesting that both waterways act as barriers to gene flow. F-statistics and exact tests of population differentiation suggest population structure on either side of both riverine barriers. Genetic differentiation across the Canal, however, was less than observed across the Chagres. Accordingly, Bayesian clustering algorithms detected between two and three populations, with localities across the older Chagres River always assigned as distinct populations. While conclusions represent a preliminary assessment of genetic structure of S. geoffroyi, this study adds to the evidence indicating that riverine barriers create genetic structure across a wide variety of taxa in the Panama Canal watershed and highlights the potential of this study area for discerning modern from historical influences on observed patterns of population genetic structure.


Diverse broad-host-range plasmids from freshwater carry few accessory genes.
Broad-host-range self-transferable plasmids are known to facilitate bacterial adaptation by spreading genes between phylogenetically distinct hosts. These plasmids typically have a conserved backbone region and a variable accessory region that encodes host-beneficial traits. We do not know, however, how well plasmids that do not encode accessory functions can survive in nature. The goal of this study was to characterize the backbone and accessory gene content of plasmids that were captured from freshwater sources without selecting for a particular phenotype or cultivating their host. To do this, triparental matings were used such that the only required phenotype was the plasmid's ability to mobilize a nonconjugative plasmid. Based on complete genome sequences of 10 plasmids, only 5 carried identifiable accessory gene regions, and none carried antibiotic resistance genes. The plasmids belong to four known incompatibility groups (IncN, IncP-1, IncU, and IncW) and two potentially new groups. Eight of the plasmids were shown to have a broad host range, being able to transfer into alpha-, beta-, and gammaproteobacteria. Because of the absence of antibiotic resistance genes, we resampled one of the sites and compared the proportion of captured plasmids that conferred antibiotic resistance to their hosts with the proportion of such plasmids captured from the effluent of a local wastewater treatment plant. Few of the captured plasmids from either site encoded antibiotic resistance. A high diversity of plasmids that encode no or unknown accessory functions is thus readily found in freshwater habitats. The question remains how the plasmids persist in these microbial communities.


Providing information about the effectiveness of treatment options to depressed people in the community: a randomized controlled trial of effects on mental health literacy, help-seeking and symptoms.
Many people who are depressed do not receive any professional help and their beliefs about the helpfulness of treatment do not always correspond with those of health professionals. To facilitate choices about treatment, the present study examined the effects of providing depressed people in the community with evidence on whether various treatment options work. A randomized controlled trial was carried out with 1094 persons selected at random from the community who screened positive for depressive symptoms and agreed to participate. Participants were mailed either an evidence-based consumer guide to treatments for depression or, as a control, a general brochure on depression. Outcomes were the rated usefulness of the information provided, changes in attitudes to depression treatments, actions taken to reduce depression, and changes in depressive symptoms, anxiety symptoms and disability. Participants rated the evidence-based consumer guide as more useful than the control brochure. Attitudes to some treatments changed. Improvements in symptoms and disability did not differ significantly between interventions. Providing people who are depressed with evidence on which treatments work produces some changes in attitudes and behaviour. However, this intervention may need to be enhanced if it is to produce symptom change.


Local canopy disturbance as an explanation for long-term increases in liana abundance.
Canopy disturbance explains liana abundance and distribution within tropical forests and thus may also explain the widespread pattern of increasing liana abundance; however, this hypothesis remains untested. We used a 10-year study (2007-2017) of 117,100 rooted lianas in an old-growth Panamanian forest to test whether local canopy disturbance explains increasing liana abundance. We found that liana density increased 29.2% and basal area 12.5%. The vast majority of these increases were associated with clonal stem proliferation following canopy disturbance, particularly in liana-dense, low-canopy gaps, which had far greater liana increases than did undisturbed forest. Lianas may be ecological niche constructors, arresting tree regeneration in gaps and thus creating a high-light environment that favours sustained liana proliferation. Our findings demonstrate that liana abundance is increasing rapidly and their ability to proliferate via copious clonal stem production in canopy gaps explains much of their increase in this and possibly other tropical forests.


Urea turnover and transfer to the digestive tract in the rabbit.
14C and 15N isotopes of urea were infused intravenously into rabbits for 6-8 h in order to measure urea synthesis and the extent of degradation in the digestive tract. The results indicate that 0.62 of the urea flux was excreted in the urine and that re-incorporation of urea-N following hydrolysis in the gut represented 0.3 of the urea synthesis rate. Sampling of metabolites from the caecum by dialysis provided an opportunity to assess the contribution of urea-N to the caecal ammonia pool. This contribution is calculated to be 0.25 of caecal ammonia turnover. Infusion of a urease (EC 126.96.36.199) inhibitor during a continuous infusion of [14C]urea into the caecum permitted the measurement of urea turnover within the caecum. Results obtained for urea entry into the caecum are contrasted with the measured urea degradation rate in the gut.


Modeling the impact of lesions in the human brain.
Lesions of anatomical brain networks result in functional disturbances of brain systems and behavior which depend sensitively, often unpredictably, on the lesion site. The availability of whole-brain maps of structural connections within the human cerebrum and our increased understanding of the physiology and large-scale dynamics of cortical networks allow us to investigate the functional consequences of focal brain lesions in a computational model. We simulate the dynamic effects of lesions placed in different regions of the cerebral cortex by recording changes in the pattern of endogenous ("resting-state") neural activity. We find that lesions produce specific patterns of altered functional connectivity among distant regions of cortex, often affecting both cortical hemispheres. The magnitude of these dynamic effects depends on the lesion location and is partly predicted by structural network properties of the lesion site. In the model, lesions along the cortical midline and in the vicinity of the temporo-parietal junction result in large and widely distributed changes in functional connectivity, while lesions of primary sensory or motor regions remain more localized. The model suggests that dynamic lesion effects can be predicted on the basis of specific network measures of structural brain networks and that these effects may be related to known behavioral and cognitive consequences of brain lesions.


Laser-induced erasable patterns in a N* liquid crystal on an iron doped lithium niobate surface.
A chiral nematic (N*) liquid crystal (LC) was hybridized with a z-cut iron doped lithium niobate (Fe:LN) substrate and exposed with a focused continuous wave diode laser beam. The N* LC layer was confined with a cover glass to provide a homogeneous LC layer thickness. Two distinct kinds of test cells were investigated, one with an uncoated glass covering slip and one with an indium tin oxide (ITO) coated cover glass. Photo generated electric fields (generated in the Fe:LN) resulted in a localized defect formation and textural transitions in the N* LC. Due to field confinement, the field induced responses were more localized in samples with ITO coated cover glasses. By scanning the laser beam on programmed trajectories, formation of persistent patterns could be achieved in the N* LC layer. Polarized optical microscopy of the exposed samples revealed that these patterns consisted of adjacent circular Frank-Pryce defects. Exposure with a slightly defocused laser beam could be applied selectively to erase these patterns. Thus, a promising method is reported to generate reconfigurable patterns, photonic motives, and touch sensitive devices in a hybridized N* LC with micron accuracy.


Amelioration of Cryptosporidium parvum infection in vitro and in vivo by targeting parasite fatty acyl-coenzyme A synthetases.
Cryptosporidium is emerging as 1 of the 4 leading diarrheal pathogens in children in developing countries. Its infections in patients with AIDS can be fatal, whereas fully effective treatments are unavailable. The major goal of this study is to explore parasite fatty acyl-coenzyme A synthetase (ACS) as a novel drug target. A colorimetric assay was developed to evaluate biochemical features and inhibitory kinetics of Cryptosporidium parvum ACSs using recombinant proteins. Anticryptosporidial efficacies of the ACS inhibitor triacsin C were evaluated both in vitro and in vivo. Cryptosporidium ACSs displayed substrate preference toward long-chain fatty acids. The activity of parasite ACSs could be specifically inhibited by triacsin C with the inhibition constant Ki in the nanomolar range. Triacsin C was highly effective against C. parvum growth in vitro (median inhibitory concentration, 136 nmol/L). Most importantly, triacsin C effectively reduced parasite oocyst production up to 88.1% with no apparent toxicity when administered to Cryptosporidium-infected interleukin 12 knockout mice at 8-15 mg/kg/d for 1 week. The findings of this study not only validated Cryptosporidium ACS (and related acyl-[acyl-carrier-protein]-ligases) as pharmacological targets but also indicate that triacsin C and analogues can be explored as potential new therapeutics against the virtually untreatable cryptosporidial infection in immunocompromised patients.


Notch destabilises maternal beta-catenin and restricts dorsal-anterior development in Xenopus.
The blastula chordin- and noggin-expressing centre (BCNE) is the predecessor of the Spemann-Mangold's organiser and also contains the precursors of the brain. This signalling centre comprises animal-dorsal and marginal-dorsal cells and appears as a consequence of the nuclear accumulation of β-catenin on the dorsal side. Here, we propose a role for Notch that was not previously explored during early development in vertebrates. Notch initially destabilises β-catenin in a process that does not depend on its phosphorylation by GSK3. This is important to restrict the BCNE to its normal extent and to control the size of the brain.


Heme compounds in dinosaur trabecular bone.
Six independent lines of evidence point to the existence of heme-containing compounds and/or hemoglobin breakdown products in extracts of trabecular tissues of the large theropod dinosaur Tyrannosaurus rex. These include signatures from nuclear magnetic resonance and electron spin resonance that indicate the presence of a paramagnetic compound consistent with heme. In addition, UV/visible spectroscopy and high performance liquid chromatography data are consistent with the Soret absorbance characteristic of this molecule. Resonance Raman profiles are also consistent with a modified heme structure. Finally, when dinosaurian tissues were extracted for protein fragments and were used to immunize rats, the resulting antisera reacted positively with purified avian and mammalian hemoglobins. The most parsimonious explanation of this evidence is the presence of blood-derived hemoglobin compounds preserved in the dinosaurian tissues.


The sequestration of hydroxyl ions by CO2 in liquid water: the physiological implications and the second function of carbonic anhydrase.
The pH changes due to bubbling CO2 through water produced anomalies which were more readily explained by an hypothesis based on electrostatic attractions between the molecules. The present studies have suggested that an hexagonal array of six carbon dioxide molecules could bind and sequester a hydroxyl anion. The binding energy of the complex is estimated to be comparable with that of a covalent compound and its dissociation may only occur at the water interface with air or at the water/hydrophobic protein interface in a protein cleft. The physiological importance lies in the consequential release of an equal number of free hydrogen ions (H3O+) and the disruption of the normal action of buffer systems in regulating the cytoplasmic pH. The counteraction of this sequestration reaction and the acid-base disturbances which result, form the second important function of carbonic anhydrase isoforms, the mechanisms of which are briefly discussed.


De-intensified adjuvant (chemo)radiotherapy versus standard adjuvant chemoradiotherapy post transoral minimally invasive surgery for resectable HPV-positive oropharyngeal carcinoma.
More than 400,000 cases of oropharyngeal squamous cell cancer (OPSCC) are diagnosed every year worldwide and this is rising. Much of the increase has been attributed to human papillomavirus (HPV). HPV-positive OPSCC patients are often younger and have significantly improved survival relative to HPV-negative patients. Traditional management of OPSCC has been with radiotherapy with or without chemotherapy, as this was shown to have similar survival to open surgery but with significantly lower morbidity. Techniques have evolved, however, with the development of computerised planning and intensity-modulated radiotherapy, and of minimally invasive surgical techniques. Acute and late toxicities associated with chemoradiotherapy are a significant burden for OPSCC patients and with an ever-younger cohort, any strategies that could decrease treatment-associated morbidity should be investigated. To assess the effects of de-intensified adjuvant (chemo)radiotherapy in comparison to standard adjuvant (chemo)radiotherapy in patients treated with minimally invasive transoral surgery (transoral robotic surgery or transoral laser microsurgery) for resectable HPV-positive oropharyngeal squamous cell carcinoma. The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; Central Register of Controlled Trials (CENTRAL); Ovid MEDLINE; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials. The date of the search was 26 April 2018. Randomised controlled trials (RCTs) in patients with carcinoma of the oropharynx (as defined by the World Health Organization classification C09, C10). Cancers included were primary HPV-positive squamous cell tumours originating from the oropharyngeal mucosa. Tumours were classified as T1-4a with or without nodal spread and with no evidence of distant metastatic spread. The intervention was minimally invasive transoral surgery followed by de-intensified adjuvant therapy (either omission of chemotherapy or reduced-dose radiotherapy). The comparator was minimally invasive transoral surgery followed by standard concurrent chemoradiotherapy or standard-dose radiotherapy. The treatments received were of curative intent and patients had not undergone any prior intervention, other than diagnostic biopsy. We used the standard methodological procedures expected by Cochrane. Our primary outcomes were overall survival (disease-related survival was to be studied where possible) and disease-free survival, measured at one, two, three and five years. Our secondary outcomes included assessment of swallowing ability and voice, measured at one, six, 12 and 24 months. We planned to use GRADE to assess the quality of evidence for each outcome. We did not identify any completed RCTs that met our inclusion criteria. However, three eligible studies are in progress:ADEPT is a phase III trial comparing postoperative radiotherapy with or without cisplatin in HPV-positive T1-4a OPSCC patients. Included patients must have received minimally invasive surgery and demonstrated extra-capsular spread from disease in the neck.ECOG-E3311 is a phase II trial of treatment for HPV-positive locally advanced OPSCC (stages III-IVa + IVb without distant metastasis). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy.PATHOS is a phase III trial of treatment for HPV-positive OPSCC (T1-3, N0-2b). Patients are stratified after minimally invasive surgery. Medium-risk patients are randomised to either standard or reduced-dose radiotherapy. High-risk patients are randomised to radiotherapy with or without concurrent cisplatin. This review highlights the current lack of high-quality randomised controlled trials studying treatment de-escalation after minimally invasive surgery in patients with HPV-positive OPSCC. However, trials that will meet the inclusion criteria for this review are in progress with results expected between 2021 and 2023.


[The intensive drug treatment of disseminated ovarian ovarian cancer].
Profound endogenous intoxication is a feature of extensive ovarian cancer (OC). In modern oncological gynecology perfection of means and ways of disintoxication is achieved through stepping up of polychemotherapy. This involves a combined use of antioxidants and enterosorption enhancing the efficiency of polychemotherapy, improving OC patients' quality of life.


Autoantibodies to Osteoprotegerin are Associated with Low Hip Bone Mineral Density and History of Fractures in Axial Spondyloarthritis: A Cross-Sectional Observational Study.
Osteoporosis is a recognised complication of axial spondyloarthritis (axSpA) and is thought to be due to functional impairment and the osteoclast-activating effects of proinflammatory cytokines. The development of autoantibodies to OPG (OPG-Ab) has been associated with severe osteoporosis and increased bone resorption in rheumatoid arthritis. In this study, we screened for the presence of OPG-Ab in axSpA and reviewed their clinical significance. We studied 134 patients, recruited from two centres in the United Kingdom. Their mean age was 47.5 years and 75% were male. Concentrations of OPG-Ab were related to bone mineral density (BMD) and fracture history using linear and logistic regression models adjusting for age, gender, disease duration and activity, body mass index and bisphosphonate use. We detected OPG-Ab in 11/134 patients (8.2%). Femoral neck and total hip BMD were significantly reduced in OPG-Ab positive patients (0.827 vs. 0.967 g/cm2, p = 0.008 and 0.868 vs. 1.028 g/cm2, p = 0.002, respectively). Regression analysis showed that the presence of OPG-Ab was independently associated with total hip osteopenia (ORadj 24.2; 95% CI 2.57, 228) and history of fractures (ORadj 10.5; 95% CI 2.07, 53.3). OPG-Ab concentration was associated with total hip BMD in g/cm2 (ß = -1.15; 95% CI -0.25, -0.04). There were no associations between OPG-Ab concentration and bone turnover markers, but free sRANKL concentrations were lower in OPG-Ab-positive patients (median 0.04 vs. 0.11 pmol/L, p = 0.050). We conclude that OPG-Ab are associated with hip BMD and fractures in axSpA suggesting that they may contribute to the pathogenesis of bone loss in some patients with this condition.


The secreted factor Ag1 missing in higher vertebrates regulates fins regeneration in Danio rerio.
Agr family includes three groups of genes, Ag1, Agr2 and Agr3, which encode the thioredoxin domain-containing secreted proteins and have been shown recently to participate in regeneration of the amputated body appendages in amphibians. By contrast, higher vertebrates have only Agr2 and Agr3, but lack Ag1, and have low ability to regenerate the body appendages. Thus, one may hypothesize that loss of Ag1 in evolution could be an important event that led to a decline of the regenerative capacity in higher vertebrates. To test this, we have studied now the expression and role of Ag1 in the regeneration of fins of a representative of another large group of lower vertebrates, the fish Danio rerio. As a result, we have demonstrated that amputation of the Danio fins, like amputation of the body appendages in amphibians, elicits an increase of Ag1 expression in cells of the stump. Furthermore, down-regulation of DAg1 by injections of Vivo-morpholino antisense oligonucleotides resulted in a retardation of the fin regeneration. These data are in a good agreement with the assumption that the loss of Ag1 in higher vertebrates ancestors could lead to the reduction of the regenerative capacity in their modern descendants.


The amyloid-β peptide: Guilty as charged?
Recent years have seen both considerable progress and controversy in the Alzheimer's disease (AD) field. After decades of slow to negligible movement towards the development of disease modifying therapies, promising outcomes in recent clinical trials with several monoclonal antibodies targeting various forms of the amyloid-β (Aβ) peptide have at last opened a possible way forward. In fact, at this point multiple anti-Aβ therapeutics are close to receiving (or have already received) regulatory approval. Although these outcomes are not without some degree of divisiveness, the fact remains that targeting amyloid for removal has finally shown at least modest efficacy in slowing the otherwise relentless progression of the disease. Although the validation of the long standing amyloid cascade hypothesis would seem to be at hand, what remains is the puzzling issue of why - if Aβ indeed causes AD - does removing it from the brain not stop the disease entirely.


A new version of the RDP (Ribosomal Database Project).
The Ribosomal Database Project (RDP-II), previously described by Maidak et al. [ Nucleic Acids Res. (1997), 25, 109-111], is now hosted by the Center for Microbial Ecology at Michigan State University. RDP-II is a curated database that offers ribosomal RNA (rRNA) nucleotide sequence data in aligned and unaligned forms, analysis services, and associated computer programs. During the past two years, data alignments have been updated and now include >9700 small subunit rRNA sequences. The recent development of an ObjectStore database will provide more rapid updating of data, better data accuracy and increased user access. RDP-II includes phylogenetically ordered alignments of rRNA sequences, derived phylogenetic trees, rRNA secondary structure diagrams, and various software programs for handling, analyzing and displaying alignments and trees. The data are available via anonymous ftp (ftp.cme.msu. edu) and WWW (http://www.cme.msu.edu/RDP). The WWW server provides ribosomal probe checking, approximate phylogenetic placement of user-submitted sequences, screening for possible chimeric rRNA sequences, automated alignment, and a suggested placement of an unknown sequence on an existing phylogenetic tree. Additional utilities also exist at RDP-II, including distance matrix, T-RFLP, and a Java-based viewer of the phylogenetic trees that can be used to create subtrees.


Pembrolizumab and tavokinogene telseplasmid electroporation in metastatic melanoma.
Tavokinogene Telseplasmid Electroporation Therapy (TAVO) and Pembrolizumab therapy is being studied in subjects with immune checkpoint inhibitor (ICI) resistant melanoma. TAVO is a novel office-based local therapy shown to be effective in patients with advanced melanoma. The technique involves the direct injection of a plasmid encoding IL-12 into an accessible tumor driven by electroporation. The tumor cells have then been shown to express high levels of IL-12 resulting in a local inflammatory response within the tumor microenvironment. The patient with stage IIB, pT3b melanoma was treated with primary tumor resection and found to have a negative sentinel node biopsy. She subsequently developed regional recurrence and was treated with inguinal lymphadenectomy and adjuvant Nivolumab. Despite therapy, she had progression of disease with skin and subcutaneous metastases (in-transit lesions), brain and liver lesions, hilar and iliac nodal disease. She was transitioned to nivolumab + ipilimumab, and Talimogene Laherparepvec (T-VEC) therapy for the in-transit lesions, without success. Stereotactic radiosurgery was used for the brain metastasis. Groin subcutaneous and in-transit lesions were treated with TAVO and intravenous pembrolizumab. Serial physical exams and CT scans were used to assess response. All lesions treated with TAVO resolved. An abscopal response was also noted: hilar and mediastinal lymphadenopathy resolved. The liver mass and pelvic lymphadenopathy decreased in size, and her brain metastasis remained stable after radiation. This case suggests that combination TAVO and Pembrolizumab is a safe and effective local treatment for ICI resistant metastatic melanoma in the setting of rheumatoid arthritis. An abscopal effect was also noted through control of systemic disease.


Improving PET-based physiological quantification through methods of wavelet denoising.
The goal of this study was to evaluate methods of multidimensional wavelet denoising on restoring the fidelity of biological signals hidden within dynamic positron emission tomography (PET) images. A reduction of noise within pixels, between adjacent regions, and time-serial frames was achieved via redundant multiscale representations. In analyzing dynamic PET data of healthy volunteers, a multiscale method improved the estimate-to-error ratio of flows fivefold without loss of detail. This technique also maintained accuracy of flow estimates in comparison with the "gold standard," using dynamic PET with O15-water. In addition, in studies of coronary disease patients, flow patterns were preserved and infarcted regions were well differentiated from normal regions. The results show that a wavelet-based noise-suppression method produced reliable approximations of salient underlying signals and led to an accurate quantification of myocardial perfusion. The described protocol can be generalized to other temporal biomedical imaging modalities including functional magnetic resonance imaging and ultrasound.


Exercise training in rats impairs the replenishment of white adipose tissue after partial lipectomy.
The aim of this study was to evaluate the effect of exercise training on the metabolism of rats following the partial removal of fat pads. Three-month-old male Wistar rats were subjected to the partial removal (L) of retroperitoneal white adipose tissue (RET) and epididymal white adipose tissue (EPI), or a sham operation (Sh). Seven days after surgery, both sets of rats were subdivided into exercised (LE or ShE) (swimming 90 min/day, 5 days/week, 6 weeks) and sedentary (LS or ShS) groups. Partial removal of the fat pads increased the lipogenesis rates in both the RET and EPI and decreased the weight and lypolysis rate of the EPI, while the RET weight was not significantly affected by lipectomy. In both lipectomized and sham-operated groups, exercise training caused a reduction in carcass lipid content, food intake, RET and EPI weights, and RET lipogenesis rate. On the other hand, the exercise training increased the percentage of diet-derived lipid accumulation in both tissues, either in sham and lipectomized rats. These results confirmed that regrowth is not uniform and depends on the particular fat pad that is excised. They also demonstrated that exercise training following the partial removal of fat pads modified adipose tissue metabolism, impaired the replenishment of adipose tissue, and decrease body adiposity.


[The effect of the glycoside strophanthin K on the ultrastructure of the cardiomyocytes in the pro-oxidant zone of the myocardium in rats with experimental heart failure].
The effect of the cardiotonic strophanthin K on the ultrastructure of cardiomyocytes in the "pro-oxidant zone" in hypercatecholemia was studied in Wistar rats with experimental cardiac insufficiency (ECI). In ECI two differently directed processes, compensatory and degenerative, develop in the "pro-oxidant zone". After administration of strophanthin K the degenerative processes in the "pro-oxidant zone" increased: the number of degenerated cardiomyocytes was 41.9 +/- 1.4% in ECI and 85.35 +/- 3.4% after strophanthin administration (p > 0.99).


Melatonin and sirtuins: A "not-so unexpected" relationship.
Epigenetic modifications, including methylation or acetylation as well as post-transcriptional modifications, are mechanisms used by eukaryotic cells to increase the genome diversity in terms of differential gene expression and protein diversity. Among these modifying enzymes, sirtuins, a class III histone deacetylase (HDAC) enzymes, are of particular importance. Sirtuins regulate the cell cycle, DNA repair, cell survival, and apoptosis, thus having important roles in normal and cancer cells. Sirtuins can also regulate metabolic pathways by changing preference for glycolysis under aerobic conditions as well as glutaminolysis. These actions make sirtuins a major target in numerous physiological processes as well as in other contexts such as calorie restriction-induced anti-aging, cancer, or neurodegenerative disease. Interestingly, melatonin, a nighttime-produced indole synthesized by pineal gland and many other organs, has important cytoprotective effects in many tissues including aging, neurodegenerative diseases, immunomodulation, and cancer. The pleiotropic actions of melatonin in different physiological and pathological conditions indicate that may be basic cellular targeted for the indole. Thus, much research has focused attention on the potential mechanisms of the indole in modulating expression and/or activity of sirtuins. Numerous findings report a rise in activity, especially on SIRT1, in a diversity of cells and animal models after melatonin treatment. This contrasts, however, with data reporting an inhibitory effect of melatonin on this sirtuin in some tumor cells. This review tabulates and discusses the recent findings relating melatonin with sirtuins, particularly SIRT1 and mitochondrial SIRT3, showing the apparent dichotomy with the differential actions documented in normal and in cancer cells.


Hepatic Capillariasis- Drug Targets.
Zoonotic infections are increasingly becoming public health menaces and are usually transmitted to humans due to unsuitable environmental conditions. One of them is hepatic capillariasis, caused by the parasite Capillaria hepatica, primarily a disease of rodents, with hepatic manifestations in humans. Although its prevalence is very low, it can cause significant morbidity and mortality, with cases reported from all over the world. The main infective form for humans is the embryonated egg of the parasite, which hatches in the intestine and ultimately colonize the liver. The larvae mature and reproduce, and eventually form embryonated eggs, which cause chronic focal inflammation and septal hepatic fibrosis. Clinical presentation mainly consists of fever, abdominal pain, hepatomegaly and eosinophilia. Spurious infection with unembryonated eggs cause gastrointestinal symptoms. Diagnostic modalities include liver biopsy, ultrasonography, CT scan, immunological tests like ELISA and IIFT. The infection can be treated mainly with a combination of benzimidazoles like thiabendazole, mebendazole and albendazole; with corticosteroids. The study emphasizes the need for hepatic capillariasis to be considered as a differential diagnosis in cases of suspected hepatitis, leptospirosis, abdominal lymphadenopathy or other hepatic or parasitic infections prevalent in the region concerned; and meticulously assess the cases to facilitate early diagnosis and prompt treatment, thus reducing the distress faced by patients.


Postoperative Cognitive Decline After Cardiac Surgery: A Narrative Review of Current Knowledge in 2019.
The growing number of publications concerning postoperative cognitive decline (POCD) after cardiac surgery is indicative of the health-related and economic-related importance of this intriguing issue. Significantly, the reported POCD incidence over the years has remained steady due to various unresolved challenges regarding the examination of this multidisciplinary topic. In particular, a universally accepted POCD definition has not been established, and the pathogenesis is still vaguely understood. However, numerous recent studies have focused on the role of the inflammatory response to a surgical procedure in POCD occurrence. Therefore, this traditional narrative review summarizes and evaluates the latest findings, with special attention paid to the difficulties of defining POCD as well as the involvement of inflammation in POCD development. We searched the MEDLINE, Scopus, PsycINFO and CENTRAL databases for the best evidence, which was classified according to the Oxford Centre for Evidence-based Medicine. To our knowledge, this is the first narrative review that identified class-1 evidence (systematic review of randomized trials), although most evidence is still at class-2 or below. Furthermore, we revealed that defining POCD is a very controversial matter and that the inflammatory response plays an important role in the mutually overlapping processes included in POCD development. Thus, developing the definition of POCD represents an absolute priority in POCD investigations, and the inflammatory response to cardiac surgery merits further research.