Evaluation of Complications After Open Reduction and Internal Fixation of Mandibular Condylar Base and Neck Fractures Using Trapezoidal Plates.
The purpose of the study was to evaluate the different fracture pattern of patients being treated with trapezoidal plate fixation of condylar base and neck fractures using the AOCMF Classification System to determine specific fracture pattern that are associated with failure of trapezoidal plate fixation. Ten patients with mandibular condylar base and neck fractures underwent internal fixation using trapezoidal plates. Fractures of the condylar process were classified according to the AOCMF Classification System using computed tomography data. The fracture pattern was compared to complications according to hardware failure such as plate or screw loosening and plate fracture. Plate and screw loosening of trapezoidal plates for fixation of condylar base and neck fractures was associated with fracture location in the neck region and major fragment displacement with contact loss between the proximal and distal fragment of the fracture. Further investigations such as finite-element analysis of different plating systems for fixation of condylar neck fractures are necessary to establish the optimal fixation technique for condylar neck fractures.


Glutamate Racemase Is the Primary Target of β-Chloro-d-Alanine in Mycobacterium tuberculosis.
The increasing global prevalence of drug resistance among many leading human pathogens necessitates both the development of antibiotics with novel mechanisms of action and a better understanding of the physiological activities of preexisting clinically effective drugs. Inhibition of peptidoglycan (PG) biosynthesis and cross-linking has traditionally enjoyed immense success as an antibiotic target in multiple bacterial pathogens, except in Mycobacterium tuberculosis, where it has so far been underexploited. d-Cycloserine, a clinically approved antituberculosis therapeutic, inhibits enzymes within the d-alanine subbranch of the PG-biosynthetic pathway and has been a focus in our laboratory for understanding peptidoglycan biosynthesis inhibition and for drug development in studies of M. tuberculosis During our studies on alternative inhibitors of the d-alanine pathway, we discovered that the canonical alanine racemase (Alr) inhibitor β-chloro-d-alanine (BCDA) is a very poor inhibitor of recombinant M. tuberculosis Alr, despite having potent antituberculosis activity. Through a combination of enzymology, microbiology, metabolomics, and proteomics, we show here that BCDA does not inhibit the d-alanine pathway in intact cells, consistent with its poor in vitro activity, and that it is instead a mechanism-based inactivator of glutamate racemase (MurI), an upstream enzyme in the same early stage of PG biosynthesis. This is the first report to our knowledge of inhibition of MurI in M. tuberculosis and thus provides a valuable tool for studying this essential and enigmatic enzyme and a starting point for future MurI-targeted antibacterial development.


Metabolic polymorphisms and the micronucleus frequency in buccal epithelium of adolescents living in an urban environment.
Micronuclei and other biomarkers were evaluated in oral cells from 11- to 16-year-old girls living in a foster home in the central area of México City. Variables analyzed for possible association with these biomarkers include smoking habits, body mass index, metabolic polymorphisms for NAT1 and GSTM1 and whether the cells were obtained from the cheek or pharynx. The results indicated that individuals having the NAT1*10 homozygous genotype showed a significant increase in chromatin buds and binucleated cells. When the damage in the cheek was compared with damage in the pharynx, a significant increase in micronuclei and binucleated cells was found for the latter tissue in all the individuals analyzed.


Linezolid treatment for osteomyelitis due to vancomycin-resistant Enterococcus faecium.
The incidence of nosocomial infections caused by vancomycin-resistant enterococci has risen substantially during the past 15 years. We report the use of linezolid for the successful treatment of hip prosthesis infection associated with osteomyelitis due to vancomycin-resistant Enterococcus faecium.


Urinary beta 2-microglobulin excretion and renal lithiasis.
We assessed beta 2-microglobulin excretion in 42 active calcium oxalate stone-formers, 16 active struvite stone-formers, 4 active uric acid stone-formers, 14 inactive stone-formers and 21 non-stone-forming controls. The average excretion value was within normal limits for all groups and no significant differences existed. These observations coupled with previous findings of increased low molecular weight urinary proteins in active calcium oxalate stone-formers suggest the existence of specific alterations in tubular function in this specific group.


Electroencephalography spectral coherence analysis during cycle ergometry in low- and high-tolerant individuals.
The main objective of this study was to further understanding of the patterns of spectral connectivity during exercise in low- and high-tolerant individuals. Thirty-nine healthy individuals (i.e., 17 low- and 22 high-tolerant participants) took part in the present study. A state-of-the-art portable electroencephalography system was used to measure the brain's electrical activity during an incremental exercise test performed until the point of volitional exhaustion on a cycle ergometer. Spectral coherence was used to explore the patterns of connectivity in the frontal, central, and parietal regions of the brain. Physiological, perceptual, and affective responses were assessed throughout the exercise bout. The spontaneous eyeblink rate was also calculated prior to commencement and upon completion of the exercise trial as an indirect assessment of the dopaminergic system. The present findings indicate that high-tolerant individuals reported lower levels of perceived activation, especially during the preliminary stages of the exercise test. Participants in the high-tolerance group also reported greater levels of remembered pleasure upon completion of the exercise test. The data also revealed that high-tolerant individuals exhibited increased connectivity of theta waves between frontal, central, and parietal electrode sites and increased connectivity of beta waves, primarily within the parietal cortex. Correlational analysis indicated the possibility that low- and high-tolerant individuals make use of different neural networks to process and regulate their psychophysiological state during exercise-related situations. This strategy could potentially represent a conscious decision to downregulate affective arousal and facilitate the neural control of working muscles during situations of physical stress.


Analysis of the Escherichia coli genome. III. DNA sequence of the region from 87.2 to 89.2 minutes.
The DNA sequence of 96.5 kilobases of the Escherichia coli K-12 genome has been determined, spanning the region between rrnA at 87.2 minutes and katG at 89.2 minutes on the genetic map. The sequence includes 84 open reading frames, of which 46 code for unidentified proteins. Six previously mapped but unsequenced genes have been identified in this span: mob, fdhD, rhaD, rhaA, rhaB, and kdgT. In addition, five new genes have been assigned: the heat shock genes hsIU and hsIV, and the genes fdoG, fdoH, and fdoI, which encode the three subunits of formate dehydrogenase-O. The arrangement of the genes relative to possible promoters and terminators suggests 57 potential transcription units. Other features include the precise location of the bacteriophage P2 attachment site attP2II, and eleven REP elements, including one containing 9 REP sequences--one of the largest such elements known. This segment brings the total length of contiguous finished sequence to 325 kilobases.


IL-6 is the principal factor produced by synovia of patients with rheumatoid arthritis that induces B-lymphocytes to secrete immunoglobulins.
First, IL-6 is produced by synovial tissue of patients with rheumatoid arthritis (RA) and is the principal mediator produced by that tissue inducing differentiation of B-lymphocytes into antibody-forming cells. The Leu-1+ subset of B-lymphocytes is induced by IL-6 to secrete rheumatoid factor (IgM with anti-Fc gamma specificity). Second, the main cell types producing IL-6 in cells dissociated from RA synovial tissue are mononuclear leukocytes. Connective tissue type cells (synoviocytes) cultured from RA synovial tissue produce IL-6 in response to IL-1 beta, and IL-6 formation is increased by TGF-beta. Glucocorticoids strongly inhibit and PGE2 slightly inhibits IL-1-induced IL-6 mRNA expression in synoviocytes. Production of IL-6 increases when undissociated RA synovial tissue is maintained in culture, thus suggesting release from inhibition by a factor or factors not yet identified. Third, the major known local effect of IL-6 in RA synovial tissue is the augmentation of antibody formation and the major known systemic effect is the induction of the synthesis by the liver of acute-phase proteins, especially C-reactive protein. Levels of circulating C-reactive protein are reported to decrease in RA patients receiving long-acting antirheumatic drugs, which would be consistent with the interpretation that immature monocyte-derived macrophages are major producers of IL-6 in these patients.


Study of Caspase 8 Inhibition for the Management of Alzheimer's Disease: A Molecular Docking and Dynamics Simulation.
Alzheimer's disease (AD) is the most common type of dementia and usually manifests as diminished episodic memory and cognitive functions. Caspases are crucial mediators of neuronal death in a number of neurodegenerative diseases, and caspase 8 is considered a major therapeutic target in the context of AD. In the present study, we performed a virtual screening of 200 natural compounds by molecular docking with respect to their abilities to bind with caspase 8. Among them, rutaecarpine was found to have the highest (negative) binding energy (-6.5 kcal/mol) and was further subjected to molecular dynamics (MD) simulation analysis. Caspase 8 was determined to interact with rutaecarpine through five amino acid residues, specifically Thr337, Lys353, Val354, Phe355, and Phe356, and two hydrogen bonds (ligand: H35-A: LYS353:O and A:PHE355: N-ligand: N5). Furthermore, a 50 ns MD simulation was conducted to optimize the interaction, to predict complex flexibility, and to investigate the stability of the caspase 8-rutaecarpine complex, which appeared to be quite stable. The obtained results propose that rutaecarpine could be a lead compound that bears remarkable anti-Alzheimer's potential against caspase 8.


EVOLUTION OF COURTSHIP SONG AND REPRODUCTIVE ISOLATION IN THE DROSOPHILA WILLISTONI SPECIES COMPLEX: DO SEXUAL SIGNALS DIVERGE THE MOST QUICKLY?
Reproductive isolation increases with genetic distance between species. Although sexual selection may drive divergence of sexual signals and traits, causing rapid evolution of sexual isolation, quantitative data supporting this idea are rare. We examine the rates of divergence of a species-specific courtship signal, sexual isolation, and postmating isolation in the Drosophila willistoni group. Both types of isolation increase with genetic distance and postmating isolation is the most strongly correlated with genetic divergence, suggesting this has the least variable divergence rate. Song divergence is not correlated with genetic divergence. Homoplasy in song pattern results in poorly resolved phylogenies that are different from molecular phylogenies. Song evolves more quickly than sexual isolation, which evolves more quickly than postmating isolation.


Use of Selected Clinical Preventive Services Among Adults--United States, 2007–2010.
CDC has a long history of monitoring the use of clinical preventive services to provide public health agencies, health care providers and their partners information needed to plan and implement programs that increase use of these services and improve the health of the U.S. population. Better use of clinical preventive services could prevent tens of thousands of deaths each year. With passage of the Patient Protection and Affordable Care Act of 2010 as amended by the Heathcare and Education Reconciliation Act of 2010, which expands health insurance coverage for the United States population and increases access to preventive services, there are new opportunities to promote and improve use of these valuable and life-saving services. This report provides baseline data prior to implementation of the provisions of the Affordable Care Act.


Longitudinal MR spectroscopy of neurodegeneration in multiple sclerosis with diffusion of the intra-axonal constituent N-acetylaspartate.
Multiple sclerosis (MS) is a pathologically complex CNS disease: inflammation, demyelination, and neuroaxonal degeneration occur concurrently and may depend on one another. Current therapies are aimed at the immune-mediated, inflammatory destruction of myelin, whereas axonal degeneration is ongoing and not specifically targeted. Diffusion-weighted magnetic resonance spectroscopy can measure the diffusivity of metabolites in vivo, such as the axonal/neuronal constituent N-acetylaspartate, allowing compartment-specific assessment of disease-related changes. Previously, we found significantly lower N-acetylaspartate diffusivity in people with MS compared to healthy controls (Wood et al., 2012) suggesting that this technique can measure axonal degeneration and could be useful in developing neuroprotective agents. In this longitudinal study, we found that N-acetylaspartate diffusivity decreased by 8.3% (p < 0.05) over 6 months in participants who were experiencing clinical or MRI evidence of inflammatory activity (n = 13), whereas there was no significant change in N-acetylaspartate diffusivity in the context of clinical and radiological stability (n = 6). As N-acetylaspartate diffusivity measurements are thought to more specifically reflect the intra-axonal space, these data suggest that N-acetylaspartate diffusivity can report on axonal health on the background of multiple pathological processes in MS, both cross-sectionally and longitudinally.


Endothelial-derived von Willebrand factor accelerates fibrin clotting within engineered microvessels.
Von Willebrand factor (VWF) is classically associated with primary hemostasis and platelet-rich arterial thromboses, but recently has also been implicated in fibrin clotting and venous thrombosis. Direct interaction between fibrin and VWF may mediate these processes, although prior reports are conflicting. We combined two complementary platforms to characterize VWF-fibrin(ogen) interactions and identify their potential physiologic significance. Engineered microvessels were lined with human endothelial cells, cultured under flow, and activated to release VWF and form transluminal VWF fibers. Fibrinogen, fibrin monomers, or polymerizing fibrin were then perfused, and interactions with VWF evaluated. Thrombin and fibrinogen were perfused into living versus paraformeldahyde-fixed microvessels and the pressure drop across microvessels monitored. Separately, protein binding to tethered VWF was assessed on a single-molecule level using total internal reflection fluorescence (TIRF) microscopy. Within microvessels, VWF fibers colocalized with polymerizing fibrin, but not fibrinogen. TIRF microscopy showed no colocalization between VWF and fibrinogen or fibrin monomers in a microfluidic flow chamber across a range of shear rates and protein concentrations. Thrombin-mediated fibrin polymerization within living microvessels triggered endothelial VWF release, increasing the rate and amount of microvessel obstruction compared to fixed vessels with an inert endothelium. We did not identify specific binding between fibrin(ogen) and VWF at a single-molecule level. Despite this, our results suggest that rapid release of endothelial VWF during clotting may provide a physical support for fibrin polymerization and accelerate thrombosis. This interaction may be of fundamental importance for the understanding and treatment of human thrombotic disease.


Pyogenic versus amoebic liver abscesses. A comparative clinical study in a series of 58 patients.
To compare the clinical and epidemiological characteristics of patients with pyogenic liver abscess (PLA) and with amebic liver abscess (AHA) in order to determine the potential factors that may help improve diagnosis and treatment for this disease. A retrospective study of clinical histories of 45 patients with PLA and 13 with ALA, diagnosed between 1985 and 2005 in Donostia Hospital in San Sebastián. Among the 45 patients with PLA (30 men and 15 women, with a mean age of 61 years and 11 months), more than a half were cholangitic (13 cases) or were of unknown origin (15 cases). In 10 patients, diabetes was considered to be a predisposing condition. Increased ESR (> 30), leukocytosis (> 12,000), fever and abdominal pain were observed in 95.5%, 86.7%, 82.8% and 68.9%, respectively. Twenty-five patients had single abscesses. Abscess and blood cultures were positive in 77.1% and 50% of cases, respectively (44.4% with polymicrobial infection). E. coli and S. milleri were the most commonly found germs. A percutaneous drainage was performed on 22 patients. Mean hospital stay was 27 days, and overall mortality, including that related to concomitant conditions, was 7 of 45 cases.Of the 13 cases of ALA (7 men and 6 women, with mean age of 42,9 years), 2 were locally acquired. Increased AF and GGTP (> 2N), fever, leukocytosis and ESR (> 30) were observed in 92.3, 77, 70 and 61.5% of cases, respectively. There were single abscesses in 10 patients and all except one were located in the right lobe. The serological test for E. histolytica (IFF > or = 1/256) was positive in 100% of cases. A percutaneous drainage was carried out on 6 patients. Mean hospital stay was 18 days and two patients died. In our series, the clinical parameters suggesting pyogenic origin were: age 50 or older, male gender, diabetes, moderately elevated bilirubin and transaminases. In amoebic cases the associated features were being aged 45 or younger, diarrhoea, and presence of a single abscess in the right lobe. Parasitism by E. histolytica must be considered in the differential diagnosis of liver abscesses, even with no epidemiological clinical history of travel and/or immigration.


Cranial computed tomography associated with development of functional dependence in a community-based elderly population.
To investigate whether changes at computed tomography (CT) imaging in the ageing brain are associated with future risks for functional dependence. 160 residents aged 69 years and older at the cranial CT and were independently living in a rural community in Hokkaido, Japan. Cranial CT was performed between 1991 and 1993, graded for ventricular enlargement, sulcal enlargement, white matter change, and small infarction. Functional status was reassessed in 1998 in each participant. Multiple logistic regression analysis was performed to estimate the association of CT changes in the ageing brain with development of functional dependence over six years. Functional dependence was found in 19 residents at the second survey. After adjusting for age, sex, medical conditions, and cognitive functioning, small infarction and ventricular enlargement were significantly associated with development of functional dependence (adjusted odds ratio = 9.27 and 4.62). After controlling for age, the age-related changes on cranial CT have significant association on development of functional dependence.


Mild hypothermia alleviates brain oedema and blood-brain barrier disruption by attenuating tight junction and adherens junction breakdown in a swine model of cardiopulmonary resuscitation.
Mild hypothermia improves survival and neurological recovery after cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). However, the mechanism underlying this phenomenon is not fully elucidated. The aim of this study was to determine whether mild hypothermia alleviates early blood-brain barrier (BBB) disruption. We investigated the effects of mild hypothermia on neurologic outcome, survival rate, brain water content, BBB permeability and changes in tight junctions (TJs) and adherens junctions (AJs) after CA and CPR. Pigs were subjected to 8 min of untreated ventricular fibrillation followed by CPR. Mild hypothermia (33°C) was intravascularly induced and maintained at this temperature for 12 h, followed by active rewarming. Mild hypothermia significantly reduced cortical water content, decreased BBB permeability and attenuated TJ ultrastructural and basement membrane breakdown in brain cortical microvessels. Mild hypothermia also attenuated the CPR-induced decreases in TJ (occludin, claudin-5, ZO-1) and AJ (VE-cadherin) protein and mRNA expression. Furthermore, mild hypothermia decreased the CA- and CPR-induced increases in matrix metalloproteinase-9 (MMP-9) and vascular endothelial growth factor (VEGF) expression and increased angiogenin-1 (Ang-1) expression. Our findings suggest that mild hypothermia attenuates the CA- and resuscitation-induced early brain oedema and BBB disruption, and this improvement might be at least partially associated with attenuation of the breakdown of TJ and AJ, suppression of MMP-9 and VEGF expression, and upregulation of Ang-1 expression.


[Study on Kveim's test. Positive tests in agammaglobulinemia. Comparison with TTL in presence of Kveim's antigen].
1. -Kveim's test (KT) was carried out on 104 patients for whom the diagnostic of sarcoidosis was suspectid. The positive results of KT correlate with other clinical, radiological and histological criteria. 2. - Two patients with idiopathic agammaglobulinemia (AGG) had positive KT. In two other cases of AGG, KT was negative. Two hypothesis are discussed: a) the association of AGG and infraclinical sarcoidosis favorized by the immunological deficit; b) false positive reactions, which raise the question of the specificity of KT. 3. - Lymphocyte transformation test in the presence of Kveim's antigen (LLT-K) was carried out simultaneously with KT 46 times. Among 30 positive KT only 20 LLT-K were positive. Among 16 negative KT 3LLT-K were positive. LLT-K was the only test carried out on 47 subjects. It was negative among 19 healthy control subjects, 19 allergic subjects and 7 patients suspected of sarcoidosis. LTT-K was positive among 3 patients suspected of sarcoidosis and 1 patient with Hodgkin's disease. 4.- LLT-K like other in vitro tests, presents some advantages over the in vivo tests, in particular the rapidity of response. We found that LTT-K was less often positive when compared with KT. The question of specificity is also raised for LTT-K.


[Clinicopathologic study of primary angiosarcoma of thyroid].
To investigate the clinicopathologic characteristics of primary angiosarcoma in thyroid. Three cases of primary angiosarcoma in thyoid were analyzed by gross examination, light microscopy and immunohistochemical staining, as well as related literatures were reviewed. The patients included 2 males and 1 female. The age of patients ranged from 52 to 78 years. The tumors showed an infiltrating histological pattern. Irregular, anastomosing gaping vascular channels were usually evident, and intravascular papillary fronds were occasionally present. In other areas, tumors featured a solid pattern of growth with cells arranged in sheets and nests with no intervening stroma. The neoplastic cells were epithelioid, spindled or polygonal-shaped with abundant eosinophilic cytoplasm and round, large, vesicular nuclei containing prominent nucleoli. The tumors showed brisk mitotic activity and necrosis. Immunohistochemical study revealed that the tumor cells were positive for CD31, ERG, Fli1, CD34, FⅧRAg and CKpan to different extents. Primary epithelioid angiosarcoma of the thyroid is a rare, high-grade malignancy that may be misdiagnosed as other malignancies, especially anaplastic thyroid carcinoma. Recognizing its clinicopathologic characters and combined application of specific vascular endothelial immunohistochemical markers is important to avoid confusion with other lesions.


High-level hemicellulosic arabinose predominately affects lignocellulose crystallinity for genetically enhancing both plant lodging resistance and biomass enzymatic digestibility in rice mutants.
Rice is a major food crop with enormous biomass residue for biofuels. As plant cell wall recalcitrance basically decides a costly biomass process, genetic modification of plant cell walls has been regarded as a promising solution. However, due to structural complexity and functional diversity of plant cell walls, it becomes essential to identify the key factors of cell wall modifications that could not much alter plant growth, but cause an enhancement in biomass enzymatic digestibility. To address this issue, we performed systems biology analyses of a total of 36 distinct cell wall mutants of rice. As a result, cellulose crystallinity (CrI) was examined to be the key factor that negatively determines either the biomass enzymatic saccharification upon various chemical pretreatments or the plant lodging resistance, an integrated agronomic trait in plant growth and grain production. Notably, hemicellulosic arabinose (Ara) was detected to be the major factor that negatively affects cellulose CrI probably through its interlinking with β-1,4-glucans. In addition, lignin and G monomer also exhibited the positive impact on biomass digestion and lodging resistance. Further characterization of two elite mutants, Osfc17 and Osfc30, showing normal plant growth and high biomass enzymatic digestion in situ and in vitro, revealed the multiple GH9B candidate genes for reducing cellulose CrI and XAT genes for increasing hemicellulosic Ara level. Hence, the results have suggested the potential cell wall modifications for enhancing both biomass enzymatic digestibility and plant lodging resistance by synchronically overexpressing GH9B and XAT genes in rice.


Optimized nucleus isolation protocol from frozen mouse tissues for single nucleus RNA sequencing application.
The single cell RNA sequencing technique has been particularly used during the last years, allowing major discoveries. However, the widespread application of this analysis has showed limitations. Indeed, the direct study of fresh tissues is not always feasible, notably in the case of genetically engineered mouse embryo or sensitive tissues whose integrity is affected by classical digestion methods. To overcome these limitations, single nucleus RNA sequencing offers the possibility to work with frozen samples. Thus, single nucleus RNA sequencing can be performed after genotyping-based selection on samples stocked in tissue bank and is applicable to retrospective studies. Therefore, this technique opens the field to a wide range of applications requiring adapted protocols for nucleus isolation according to the tissue considered. Here we developed a protocol of nucleus isolation from frozen murine placenta and pancreas. These two complex tissues were submitted to a combination of enzymatic and manual dissociation before undergoing different steps of washing and centrifugation. The entire protocol was performed with products usually present in a research lab. Before starting the sequencing process, nuclei were sorted by flow cytometry. The results obtained validate the efficiency of this protocol which is easy to set up and does not require the use of commercial kits. This specificity makes it adaptable to different organs and species. The association of this protocol with single nucleus RNA sequencing allows the study of complex samples that resist classical lysis methods due to the presence of fibrotic or fatty tissue, such as fibrotic kidney, tumors, embryonic tissues or fatty pancreas.


Violation of prophylactic vancomycin administration timing is a potential risk factor for rate of surgical site infections in cardiac surgery patients: a prospective cohort study.
Intensivists and cardiothoracic surgeons are commonly worried about surgical site infections (SSIs) due to increasing length of stay (LOS), costs and mortality. The antimicrobial prophylaxis is one of the most important tools in the prevention of SSIs. The objective of this study was to investigate the relationship between the timing of antimicrobial prophylaxis administration and the rate of SSIs. A prospective cohort study was carried out over 1-year period in all consecutive adult patients undergoing elective cardiac surgery. The population was stratified in patients whose antimicrobial prophylaxis administration violated or not the vancomycin timing protocol (i.e., when the first skin incision was performed before the end of vancomycin infusion). To compare SSI rates, the cohort was further stratified in patients at low and high risk of developing SSIs. Over the study period, 1020 consecutive adult patients underwent cardiac surgery and according to study inclusion criteria, 741 patients were prospectively enrolled. A total of 60 SSIs were identified for an overall infection rate of 8.1%. Vancomycin prophylaxis timing protocol was violated in 305 (41%) out of 741 enrolled patients. SSIs were observed in 3% of patients without violation of the antimicrobial prophylaxis protocol (13/436) compared with 15.4% of patients with a violation of the timing protocol (47/305) (P < 0.0001). Patients at low risk with protocol violation had a higher occurrence of SSIs (P = 0.004) and mortality (P = 0.03) versus patients at low risk without protocol violation. Similarly, patients at high risk with protocol violation had a higher occurrence of SSIs (P < 0.001) and mortality (P < 0.001) versus patients at high risk without protocol violation. The logistic regression analysis showed that internal mammary artery use (P = 0.025), surgical time (P < 0.001), intensive care unit (ICU) LOS (P = 0.002), high risk of developing SSIs (P < 0.001) and protocol violation (P < 0.001) were risk factors for SSI occurrence as well as age (P = 0.003), logistic EuroSCORE (P < 0.001), ICU LOS (P < 0.001), mechanical ventilation time (P < 0.001) and protocol violation (P < 0.001) were risk factors for mortality. This study showed that violation of the timing of prophylactic vancomycin administration significantly increased the probability of SSIs and mortality from infectious cause in cardiac surgery patients.


Serum-based DNA methylation biomarkers in colorectal cancer: potential for screening and early detection.
Colorectal cancer (CRC) is the third most common cause of cancer-related death in the United States. Early identification and treatment of pre-cancerous colorectal lesions, or node-negative CRC are highly effective interventions that substantially reduce disease-specific mortality. Colonoscopy remains a highly effective primary screening tool based on its excellent diagnostic accuracy, and its ability to remove pre-cancerous lesions. However, the nature of the procedure limits compliance with colonoscopy intended for population-based CRC screening. A significant advance in the screening and care of these patients could be realized by blood-based biomarkers, which could accurately identify patients at-risk for CRC development whom might benefit from early and/or more frequent surveillance for disease. We reviewed and herein discuss the potential for serum based DNA methylation biomarkers for screening and early detection of CRC.


Effect of substance P on catecholamine secretion from rat adrenal medulla in situ.
Splanchnic nerve stimulation caused a frequency-dependent increase in catecholamine (CA) secretion with a maximum at 10 Hz from adrenal medulla of WKY rats in situ. Substance P (SP(1-11)) had no effect on the basal output of CA. During nerve stimulation, however, SP(1-11) decreased only the adrenaline (A) secretion by 18% at 10 Hz and by 55% at 20 Hz (p less than 0.05), whereas the noradrenaline (NA) secretion remained unchanged. These results provide further evidence that SP(1-11) may modulate frequency-dependently the secretion of CA from adrenal medulla in situ.


Low-frequency ultrasound treatment of chronic venous ulcers.
In a randomized controlled clinical trial, the properties of low-frequency ultrasound in the treatment of chronic venous ulcers were investigated. Thirty-eight patients with chronic ulcerations of the legs caused by chronic venous insufficiency were randomly assigned to receive either conventional therapy alone or conventional therapy plus additional 30 kHz ultrasound treatment. Patients with other conditions that may impair wound healing such as diabetes mellitus or arterial disease were excluded. The ultrasound treatment consisted of 10 minutes of foot bathing with application of 30 kHz ultrasound 100 mW/cm(2) three times a week. Response was evaluated with the use of planimetry of the ulcer area and compared with controls after 3 and 8 weeks. After 3 weeks of treatment (and to a greater extent after 8 weeks of treatment) the ultrasound group showed a markedly better response than the control group. Although the control group showed a mean decrease of 11% in the ulcerated area after 8 weeks, in the ultrasound group the mean ulcerated area decreased by 41% (p < 0.05). There were only mild side effects in some of the patients treated with ultrasound. In conclusion, application of low-frequency ultrasound may be a helpful treatment option in chronic venous leg ulcers.


Edematous disorders: pathophysiology of renal sodium and water retention and treatment with diuretics.
The pathogenesis of renal sodium and water retention in cardiac failure, cirrhosis, and the nephrotic syndrome may be explained by the unifying hypothesis of body fluid volume regulation. According to this hypothesis, underfilling of the arterial vascular compartment initiates a sequence of events, including activation of various neurohormonal vasoconstrictor systems, which results in enhanced renal sodium and water reabsorption, the failure to escape from the sodium-retaining effect of aldosterone, and renal resistance to atrial natriuretic peptide. In patients with low-output cardiac failure, a decrease in cardiac output results in arterial underfilling. Peripheral arterial vasodilation diminishes the fullness of the arterial vascular compartment in patients with high-output cardiac failure and cirrhosis. In the nephrotic syndrome, the decrease in plasma oncotic pressure due to hypoalbuminemia initiates arterial underfilling. The factors that are responsible for the peripheral arterial vasodilation in patients with cirrhosis remain obscure. Diuretics are initially effective in reducing the excess of total-body sodium and water in edematous patients. Loop diuretics, with or without metolazone or a thiazide diuretic, are quite useful in patients with heart failure. In cirrhosis and the nephrotic syndrome, the specific aldosterone antagonist spironolactone, alone or in combination with other diuretics, has proven to be highly efficacious. However, in all instances, the emergence of diuretic resistance represents a major limitation of diuretic therapy for the edematous patient. This diuretic resistance may be mediated by further activation of vasoconstrictor, antinatriuretic neurohormones.


Perceptions of credibility of sexual abuse victims across generations.
The success of prosecutions of perpetrators of sexual abuse often depends substantially upon the perceived credibility of the victim witness. However, perceptions of credibility may vary by generation of the observer, and the constitution of juries may therefore lead to bias. In this study we examined whether perceptions of credibility of female victims of sexual abuse varied across generation Y, generation X, "baby boomers", and "builders". One hundred and twenty-eight jury-eligible members of the community from each generation (N=512) responded to ten questions assessing the perceived believability, competence, trustworthiness, demeanour and sexual naiveté of females providing testimony related to alleged sexual abuse. Although consistent between-generation differences were not found for all questions, or all four groups of generational cohorts, in instances where significant differences were found, it was consistently the older generation groups (builders and baby boomers) that attributed less credibility to the victim than the younger generation groups (generation Y and generation X). The implications of these findings are discussed.


Critical care bed growth in the United States. A comparison of regional and national trends.
Although the number of intensive care unit (ICU) beds in the United States is increasing, it is unknown whether this trend is consistent across all regions. We sought to better characterize regional variation in ICU bed changes over time and identify regional characteristics associated with these changes. We used data from the Centers for Medicare and Medicaid Services and the U.S. Census to summarize the numbers of hospitals, hospital beds, ICU beds, and ICU occupancy at the level of Dartmouth Atlas hospital referral region from 2000 to 2009. We categorized regions into quartiles of bed change over the study interval and examined the relationship between change categories, regional characteristics, and population characteristics over time. From 2000 to 2009 the national number of ICU beds increased 15%, from 67,579 to 77,809, mirroring population. However, there was substantial regional variation in absolute changes (median, +16 ICU beds; interquartile range, -3 to +51) and population-adjusted changes (median, +0.9 ICU beds per 100,000; interquartile range, -3.8 to +5.9), with 25.0% of regions accounting for 74.8% of overall growth. At baseline, regions with increasing numbers of ICU beds had larger populations, lower ICU beds per 100,000 capita, higher average ICU occupancy, and greater market competition as measured by the Herfindahl-Hirschman Index (P < 0.001 for all comparisons). National trends in ICU bed growth are not uniformly reflected at the regional level, with most growth occurring in a small number of highly populated regions.


Selective Radical Transfer in a Series of Nonheme Iron(III) Complexes.
A series of nonheme iron complexes, FeIII(BNPAPh2O)(Lax)(Leq) (Lax/eq = N3-, NCS-, NCO-, and Cl-) have been synthesized using the previously reported BNPAPh2O- ligand. The ferrous analogs FeII(BNPAPh2O)(Lax) (Lax = N3-, NCS-, and NCO-) were also prepared. The complexes were structurally characterized using single crystal X-ray diffraction, which shows that all the FeIII complexes are six-coordinate, with one anionic ligand (Lax) in the H-bonding axial site and the other anionic ligand (Leq) in the equatorial plane, cis to the Lax ligand. The reaction of FeIII(BNPAPh2O-)(Lax)(Leq) with Ph3C• shows that one ligand is selectively transferred in each case. A selectivity trend emerges that shows •N3 is the most favored for transfer in each case to the carbon radical, whereas Cl• is the least favored. The NCO and NCS ligands showed an intermediate propensity for radical transfer, with NCS > NCO. The overall order of selectivity is N3 > NCS > NCO > Cl. In addition, we also demonstrated that H-bonding has a small effect on governing product selectivity by using a non-H-bonded ligand (DPAPh2O-). This study demonstrates the inherent radical transfer selectivity of nonhydroxo-ligated nonheme iron(III) complexes, which could be useful for efforts in synthetic and (bio)catalytic C-H functionalization.


The perceptual responses to occluded exercise.
The purpose was to determine repetitions to failure and perceptual responses to exercise with and without occlusion. 15 subjects participated in a randomized crossover study of 3 trials. The first determined one repetition maximum (1RM) on the leg extension. Subjects were then assigned to an occlusion (OCC) or control (CON) group. After trial 2, subjects crossed over to the opposite trial. Knee wraps (KW) were placed around the upper thigh of each leg during OCC. Subjects completed 2 sets of leg extensions to failure at 30% 1RM, with 30 s rest between sets. Ratings of perceived exertion (RPE) and pain (P) were taken following each set. Data were analyzed using paired sample t-tests with an alpha level of 0.01. OCC repetitions were lower for the first and second set compared to CON (p=0.001). Total work completed was significantly lower with OCC compared to CON (p=0.001). OCC RPE were higher for both the first (p=0.01) and second set (p=0.003) compared to CON. P was not different following one set but was higher with OCC over CON following the second (p=0.009). In conclusion, KW provide an OCC stimulus allowing failure to occur sooner. However, the higher perceptual responses with OCC may limit its application to the highly motivated.


Effects of tussah immunoreactive substances on growth, immunity, disease resistance against Vibrio splendidus and gut microbiota profile of Apostichopus japonicus.
Tussah immunoreactive substance (TIS) comprises a number of active chemicals with various bioactivities. The current study investigated the effects of these substances on the sea cucumber Apostichopus japonicus. The specific growth rate (SGR) of TIS-fed sea cucumbers was significantly enhanced, whereas no significant difference in SGR was observed between those soaked in antibiotics and those fed with basal diet only. TIS also improved the immune response of the animals when given at a dose of 1.0% or 2.0%, as shown by increased phagocytic, lysozyme, superoxide dismutase, alkaline phosphatase, acid phosphatase, and catalase activities following injection with live Vibrio splendidus. At a dose of 1.0% or 2.0%, TIS significantly enhanced the immune ability (P < 0.05) of the sea cucumbers, but except for lysozyme activity, other immune indices were reduced one day after the animals were injected with Vibrio splendidus. However, the values of these immune indexes were still significantly higher compared to those of the control groups (P < 0.05). Intestinal micro flora counts and high-throughput sequencing showed that dietary TIS could improve the amount of probiotic bacteria, yielding a 6-fold increase in Bacillus and 10-fold increase in Lactobacillus for sea cucumbers fed with 2.0% TIS diet compared to the control. Furthermore, TIS-containing diet also greatly reduced the number of harmful bacteria, with the number of Vibrio in sea cucumbers fed with 1%TIS diet decreased by 67% compared to the control. The results thus indicated that TIS increased the growth of sea cucumbers and enhanced their resistance to V. splendidus infection by improving the immunity of the animals. TIS also improved the gut microbiota profiles of the animals by increasing the probiotics and reducing the harmful bacteria within their guts.


Cornus officinalis prior and post-processing: Regulatory effects on intestinal flora of diabetic nephropathy rats.
Background: Diabetic nephropathy (DN) is one of the most common and serious chronic complications in the clinic. Cornus officinalis has the effects of replenishing qi and nourishing yin, tonifying liver and kidney, and it is one of the main traditional Chinese medicines used clinically to treat diabetes and its complications. However, the effect and mechanism of Cornus officinalis before and after processing on intestinal flora of diabetic nephropathy need to be further elucidated. Methods: SD rats were randomly divided into a blank group (10 rats) and DN groups (70 rats). After 4 weeks of high-sugar and high-fat diet, the DN rat model was established by intraperitoneal injection of streptozotocin. After successful modeling, the rats were randomly divided into DN model group, irbesartan group (1.35 mg·kg-1), Cornus officinalis group (281.25 mg·kg-1), wine Cornus officinalis group (281.25 mg·kg-1), wine honey Cornus officinalis group (281.25 mg·kg-1), auxiliary wine group (10 ml·kg-1), auxiliary wine honey group (10 ml·kg-1). During the observation of the rats' general state, after 6 weeks of continuous administration, the fasting blood glucose of rats in each group was detected, and the kidney index was calculated. The serum creatinine levels, urea nitrogen and 24 h urinary microalbumin were detected by enzyme-linked immunosorbent assay. The expression levels of YKL-40, Wnt4, β-catenin and TGF-β 1 mRNA in renal tissue were detected by fluorescence quantitative PCR. Hematoxylin-eosin staining was used to observe the changes in renal pathological injury in each group; GC-MS detected the changes of short chain fatty acid content. Feces were collected for 16 s high-throughput sequencing to analyze the effects of Cornus officinalis on the diversity of intestinal flora in DN before and after processing. Results: Compared with the blank group, the serum creatinine, urea nitrogen, 24 h urinary microalbumin, kidney index and fasting blood glucose in the DN model group were significantly increased (p < 0.05). The renal tissue morphology was disordered and a large number of inflammatory cells were infiltrated. The expression of YKL-40, Wnt4, β-catenin and TGF-β 1 mRNA was significantly increased (p < 0.05). Compared with the DN model group, the serum creatinine, urea. Nitrogen, 24 h urine microalbumin, kidney index and fasting blood glucose of rats in each administration group were significantly decreased (p < 0.05), and the general condition and pathological renal damage of DN rats were improved. The effect of wine honey Cornus officinalis was the best, and the expression of YKL-40, Wnt4, β-catenin and TGF-β 1 mRNA was significantly decreased (p < 0.05). In each administration group, the improvement of the above indicators in the wine honey Cornus officinalis group was significantly better than that in the raw Cornus officinalis group and wine Cornus officinalis group (p < 0.05), There was no significant difference compared with the irbesartan group (p > 0.05). Each administration group had a significant callback effect on the content of short-chain fatty acids in rat feces, with increased intestinal beneficial bacteria and decreased pathogenic bacteria. Compared with the blank group, the abundance of Firmicutes in the DN model group increased, the abundance of Bacteroidetes decreased, and the ratio showed an upward trend in the DN model group decreased. Each administration group could improve the relative abundance of the above intestinal flora in the model group to varying degrees. Conclusion: The processing of Cornus officinalis may improve the renal injury of DN rats by blocking the activation of Wnt/β-catenin signaling pathway, regulating the structural composition of intestinal microorganisms, and ultimately playing a role in renal protection.


Increasing physical activity of high intensity to reduce the prevalence of chronic diseases and improve public health.
High incidence and prevalence of chronic diseases, increasing obesity and inactivity as well as rising health expenditure represent a set of developments that cannot be considered sustainable, and will have dire long-term consequences given the increasing proportion of elderly people in our society. Based on a review of the experiences from previous large scale population-based prevention programs and the documented effects of increased physical activity and cardiorespiratory fitness on chronic diseases and its risk factors, we argue that increased physical activity, especially vigorous physical activity, is a major way to reduce the prevalence of chronic diseases and improve public health. We conclude that a coordinated population-based intervention program for improved health through increased physical activity in the entire population, with a special focus on high intensity exercise, urgently needs to be implemented nationally and internationally.


Optimal cut-off points for waist circumference in the definition of metabolic syndrome in Chile.
To identify sex-specific cut-off points for waist circumference (WC) in the definition of metabolic syndrome (MetS) for the Chilean adult population. MetS was defined as the presence of at least two out of four of the following criteria: TAG ≥1·7 mmol/l; HDL-cholesterol: <1·3 mmol/l in women and <1·0 mmol/l in men; systolic blood pressure ≥130 mmHg and/or diastolic blood pressure ≥85 mmHg; and fasting glucose ≥ 5·6 mmol/l or current treatment for diabetes. The receiver operating characteristics curve and the AUC were computed to derive the specificity and sensitivity using bootstrapping (10 000 iterations restricted to have at least between 40 and 60 % of the original population). The optimal cut-off point for the Chilean population was computed by sex. A representative sample of the Chilean population aged ≥15 years. 8182 participants (60 % women) from the three available Chilean National Health Surveys conducted in 2003, 2009-2010 and 2016-2017. WC had a good predictive ability for MetS (AUC for men 0·74 (95 % CI 0·72, 0·76); AUC for women 0·71 (95 % CI 0·68, 0·73)). The optimal cut-off points for WC, in the definition of MetS, were 92·3 cm (95 % CI 90·5, 94·4) and 87·6 cm (95 % CI 85·8, 92·1) for men and women, respectively. The mentioned cut-off points should be used for WC in the definition of MetS in Chile. As a result, the current recommendation (WHO/International Diabetes Federation) for WC, in the identification of MetS, is not supported by these findings in a representative sample of the Chilean adult population.


Impact of discharge currents on the intensity of 46.9 nm capillary discharge soft X-ray laser.
In this article, capillary discharge Ne-like argon 46.9nm soft X-ray laser has been firstly manifested with 4.8mm inner diameter alumina capillary for higher discharge currents. We have designed and installed capillary discharge setup for 4.8mm inner diameter alumina capillary to achieve intense 46.9nm laser. One dimensional Langragian Magneto-hydrodynamics (MHD) code was used to simulate the plasma conditions at the lasing time. The MHD code was used to perform the parametric studies of Z-pinch argon plasma, such as electron temperature, electron density and Ne-like argon ion density. The intensities of capillary discharge 46.9nm laser emitted from 4.8mm inner diameter alumina capillary were measured at 30, 36 and 40kA main discharge currents. According to the results, when the main current amplitude was increased from 30kA to 36kA and 40kA, the intensity of laser produced at optimum pressure increased up to 1.5 and 2 times, respectively. Moreover, we also studied the influence of predischarge current by increasing the predischarge current from 25 to 250A and investigated 140A as the best predischarge current for lasing. Hence, increasing the amplitude of main current using a comparatively larger inner diameter capillary is an effective way to improve intensity of capillary discharge 46.9nm soft X-ray laser. The maximum energy of 46.9nm laser was observed approximately 1.5mJ under best discharge conditions. The discussion has been made on the enhancement of 46.9nm laser intensity for higher main discharge currents and best predischarge current with experimental and simulated results. This is the first observation of 46.9nm laser with 4.8mm inner diameter alumina capillary.


Recent advances in the in vitro evolution of nucleic acids.
Molecular evolution allows chemists and biologists to generate nucleic acids with tailor-made binding or catalytic activities. Recent examples of nucleic acid evolution in vitro provide insights into natural ribozyme evolution and also demonstrate potential applications of evolved DNA and RNA molecules. Efforts to expand the scope of nucleic acid evolution are also underway, including the development of novel methods for exploring nucleic acid sequence-space and the incorporation of non-natural chemical functionality into nucleic acid libraries.


Spatial distribution and deployment of community-based distributors implementing integrated community case management (iCCM): Geographic information system (GIS) mapping study in three South Sudan states.
In late 2012 and in conjunction with South Sudan's Ministry of Health - National Malaria Control Program, PSI (Population Services International) conducted a comprehensive mapping exercise to assess geographical coverage of its integrated community case management (iCCM) program and consider scope for expansion. The operational research was designed to provide evidence and support for low-cost mapping and monitoring systems, demonstrating the use of technology to enhance the quality of programming and to allow for the improved allocation of resources through appropriate and need-based deployment of community-based distributors (CBDs). The survey took place over the course of three months and program staff gathered GPS (global positioning system) data, along with demographic data, for over 1200 CBDs and 111 CBD supervisors operating in six counties in South Sudan. Data was collated, cleaned and quality assured, input into an Excel database, and subsequently uploaded to geographic information system (GIS) for spatial analysis and map production. The mapping results showed that over three-quarters of CBDs were deployed within a five kilometer radius of a health facility or another CBD, contrary to program planning and design. Other characteristics of the CBD and CBD supervisor profiles (age, gender, literacy) were more closely matched with other regional programs. The results of this mapping exercise provided a valuable insight into the contradictions found between a program "deployment plan" and the realities observed during field implementation. It also highlighted an important need for program implementers and national-level strategy makers to consider the natural and community-driven diffusion of CBDs, and take into consideration the strength of the local health facilities when developing a deployment plan.


Associations of multiplicity of comorbid health conditions, serious mental illness, and health care costs.
Using a nationally representative U.S. sample, this study analyzed the effects of serious mental illness (SMI) and comorbid medical conditions on the cost of health care. The results of path model indicated that SMI and comorbid health conditions each increased total health care costs. Additionally, individuals with SMI were likely to have more comorbid medical conditions, which in turn, increased total health care costs. Findings raise awareness of an increased risk of medical conditions among individuals with SMI and the concern of high expenditures associated with comorbid SMI and medical conditions.


An extended EM algorithm for joint feature extraction and classification in brain-computer interfaces.
For many electroencephalogram (EEG)-based brain-computer interfaces (BCIs), a tedious and time-consuming training process is needed to set parameters. In BCI Competition 2005, reducing the training process was explicitly proposed as a task. Furthermore, an effective BCI system needs to be adaptive to dynamic variations of brain signals; that is, its parameters need to be adjusted online. In this article, we introduce an extended expectation maximization (EM) algorithm, where the extraction and classification of common spatial pattern (CSP) features are performed jointly and iteratively. In each iteration, the training data set is updated using all or part of the test data and the labels predicted in the previous iteration. Based on the updated training data set, the CSP features are reextracted and classified using a standard EM algorithm. Since the training data set is updated frequently, the initial training data set can be small (semi-supervised case) or null (unsupervised case). During the above iterations, the parameters of the Bayes classifier and the CSP transformation matrix are also updated concurrently. In online situations, we can still run the training process to adjust the system parameters using unlabeled data while a subject is using the BCI system. The effectiveness of the algorithm depends on the robustness of CSP feature to noise and iteration convergence, which are discussed in this article. Our proposed approach has been applied to data set IVa of BCI Competition 2005. The data analysis results show that we can obtain satisfying prediction accuracy using our algorithm in the semisupervised and unsupervised cases. The convergence of the algorithm and robustness of CSP feature are also demonstrated in our data analysis.


On the Menu: Analyzing the Macronutrients, Micronutrients, Beverages, Dietary Patterns, and Pancreatic Cancer Risk.
This narrative review summarizes the principal findings of observational studies, systematic reviews, and meta-analyses on diet and dietary patterns' role in the risk of pancreatic cancer. Etiologically pancreatic cancer is multifactorial. Evidence exists of an association between nutrients, dietary patterns, and pancreatic cancer. An extensive literature search was conducted on PubMed, Cochrane, and Google Scholar. A thorough search of articles published in English till May 2023 and related to the review was performed. The relationship between all macronutrients, micronutrients, and various dietary patterns with the risk of pancreatic cancer was assessed. It is concluded that a diet high in nutrients like red and processed meat, refined sugars, saturated and monounsaturated fats, alcohol, copper, and a Western dietary pattern can increase the likelihood of pancreatic cancer. Contrary to this, a diet consisting of fruits, vegetables, appropriate quantities of vitamins and minerals, and a Mediterranean dietary pattern is associated with a decreased risk of pancreatic cancer.


Preferences for colloid use in Scandinavian intensive care units.
Fluid resuscitation is a frequent intervention in intensive care. Colloids are widely used, but recent data suggest harm by some of these solutions. This calls for more clinical studies on this matter, but the current preferences for colloid use in Scandinavian intensive care units (ICUs) are unknown. In March-May 2007, 120 Scandinavian ICUs were invited to answer a web-based survey consisting of 18 questions on types of colloids, indications, contraindications and rationale of use. Seventy-three ICUs, of which 31 were university hospital units, answered the questionnaire. Most ICUs used both synthetic and natural colloids, and hydroxyethyl starch (HES) 130/0.4 was the preferred colloid in 59 units. Eleven ICUs had protocols for colloid use. The most frequent indication was second-line fluid for hypovolaemia, but one in three ICUs used colloids as first-line fluid. Thirty-five ICUs had contraindications, which were mainly for the use of synthetic colloids (acute renal failure 25 units, bleeding 15 units). Most units based the use of colloids on theoretical knowledge and tradition. Sixty-five and 54 ICUs were ready to change colloid use based on data from randomised trials of ICU patients showing changes in mortality or renal function, respectively. Most Scandinavian ICUs use both synthetic and natural colloids, but HES 130/0.4 is by far the preferred colloid. Few units have protocols for colloid use, but most use them for hypovolaemia, and the majority have no contraindications. Most ICUs are ready to change colloid use if randomised trials in ICU patients show changes in mortality or renal function.


Research on the presence of porcine enterovirus serotype 1 in north-eastern Italy.
The liquid-phase blocking sandwich ELISA, already developed for foot-and-mouth disease and swine vesicular disease serology, has been employed in pig sera for the antibody detection against porcine enterovirus serotype 1. ELISA-titers correlate positively with virus neutralization and their distribution show a high prevalence among the sampled pigs. The serological findings are confirmed by the isolation of a field strain of porcine enterovirus belonging to the serotype 1.


Calcitonin gene-related peptide (CGRP) modulates nociceptive trigeminovascular transmission in the cat.
Calcitonin gene-related peptide (CGRP) is released into the cranial circulation of humans during acute migraine. To determine whether CGRP is involved in neurotransmission in craniovascular nociceptive pathways, we microiontophoresed onto neurons in the trigeminocervical complex and intravenously administered the CGRP receptor antagonists alpha-CGRP-(8-37) and BIBN4096BS. Cats were anaesthetised with alpha-chloralose, and using halothane during surgical preparation. A craniotomy and C1/C2 laminectomy allowed access to the superior sagittal sinus (SSS) and recording site. Recordings of activity in the trigeminocervical complex evoked by electrical stimulation of the SSS were made. Multibarrelled micropipettes incorporating a recording electrode were used for microiontophoresis of test substances. Cells recorded received wide dynamic range (WDR) or nociceptive specific (NS) input from cutaneous receptive fields on the face or forepaws. Cell firing was increased to 25-30 Hz by microiontophoresis of L-glutamate (n = 43 cells). Microiontophoresis of alpha-CGRP excited seven of 17 tested neurons. BIBN4096BS inhibited the majority of units (26 of 38 cells) activated by l-glutamate, demonstrating a non-presynaptic site of action for CGRP. alpha-CGRP-(8-37) inhibited a similar proportion of units (five of nine cells). Intravenous BIBN4096BS resulted in a dose-dependent inhibition of trigeminocervical SSS-evoked activity (ED50 31 microg kg(-1)). The maximal effect observed within 30 min of administration. The data suggest that there are non-presynaptic CGRP receptors in the trigeminocervical complex that can be inhibited by CGRP receptor blockade and that a CGRP receptor antagonist would be effective in the acute treatment of migraine and cluster headache.


Engineering biomaterial-associated complement activation to improve vaccine efficacy.
The complement system plays an important role in innate and adaptive immunity, which suggests that complement activation could be exploited as a potential strategy for vaccine adjuvants. Here we explored the potential of chitosan-based microparticles (CS-NH2 MPs) as a vaccine adjuvant with an active surface for complement activation due to the abundance of amino groups. In vaccination studies, using recombinant anthrax protective antigen as a model antigen, compared with the control microparticles (amino-cross-linked MPs), we found that microparticles (MPs) with abundant amino groups significantly enhanced higher antigen-specific IgG titers in vivo and enhanced the production of IL-4 and IFN-γ with ex vivo restimulation. Furthermore, proliferative responses of splenocytes to ex vivo antigen restimulation were enhanced following immunization with MPs with amino groups. Overall, these results indicated that CS-NH2 MPs with a high surface density of amino groups were favorable for complement activation and immune responses. Our data provide further design principles for studies on complement-activating MPs as a vaccine platform.


Analysis of the cytolytic T-lymphocyte response to herpes simplex virus type 1 glycoprotein B during primary and secondary infection.
The immune response to herpes simplex virus type 1 (HSV-1) infection in C57BL/6 mice includes a population of major histocompatibility complex class I-restricted cytolytic T lymphocytes (CTL) that recognize the structural glycoprotein gB. To gain insight into the importance of this CTL subpopulation in vivo, gB-specific CTL present in the regional lymph nodes after a primary infection and after a reinfection of convalescent animals were analyzed. In a primary infection, gB-specific CTL precursors (CTLp) that recognized either a cell line constitutively expressing gB or cells pulsed with the optimal Kb-restricted gB epitope 498SSIEFARL505 were present at an estimated frequency of 1/12,000 compared with a frequency of 1/3,000 for CTLp which recognized cells infected with HSV-1 itself. In convalescent mice responding to reinfection, HSV-specific CTLp were present at an estimated frequency of 1/4,000 to 1/14,000. However, gB-specific CTLp could not be detected at this site. These findings suggest that CTL specific for an immunodominant epitope contribute substantially to the primary response but may not be a component of the HSV-specific CTL population that responds rapidly to reinfection in vivo.


Foreign intervention in medical education: a case study of the Rockefeller Foundation's involvement in a Thai medical school.
A case study of the process of foreign intervention in medical education in the developing world is presented. Material collected from the Rockefeller Foundation Archives on a Foundation program in Thailand is used to analyze the conditions under which foreign agencies and their personnel intervene in the development of medical professionals in the Third World and to study the problems that may occur as a result of such intervention. The importance of value consensus and the competitive advantage foreigners have in the marketing of professional models are highlighted as reasons for the diffusion of Western models of medical education throughout the developing world.


Prospectively identified deficits in sagittal plane hip-ankle coordination in female athletes who sustain a second anterior cruciate ligament injury after anterior cruciate ligament reconstruction and return to sport.
Athletes who return to sport after anterior cruciate ligament reconstruction are at increased risk of future ACL injury. Altered coordination of lower extremity motion may increase this risk. The purpose of this study was to prospectively determine if altered lower extremity coordination patterns exist in athletes who go on to sustain a 2nd anterior cruciate ligament injury. Sixty-one female athletes who were cleared to return to sport after anterior cruciate ligament reconstruction were included. Hip-ankle coordination was assessed prior to return to sport with a dynamic postural coordination task. Within 12 months, 14 patients sustained a 2nd ACL injury. Fourteen matched subjects were selected for comparative analysis. Cross-recurrence quantification analysis characterized hip-ankle coordination patterns. A group × target speed (slow vs. fast) × leg (involved vs. uninvolved) analysis of variance was used to identify differences. A main effect of group (P = 0.02) indicated that the single injury group exhibited more stable hip-ankle coordination [166.2 (18.9)] compared to the 2nd injury group [108.4 (10.1)]. A leg × group interaction was also observed (P = .04). The affected leg of the single injury group exhibited more stable coordination [M = 187.1 (23.3)] compared to the affected leg of the 2nd injury group [M = 110.13 (9.8)], P = 0.03. Hip-ankle coordination was altered in female athletes who sustained a 2nd anterior cruciate ligament injury after return to sport. Failure to coordinate lower extremity movement in the absence of normal knee proprioception may place the knee at risk.


Palliation of Truncus Arteriosus Associated With Complete Atrioventricular Canal--Results of Single Ventricle Palliation.
Truncus arteriosus associated with complete atrioventricular canal defect is rare and continues to be a surgical challenge with high morbidity and mortality. In the absence of extension of the ventricular septal defect to the outlet septum, biventricular repair is precluded, and single ventricle palliation remains the only option. We present our experience with five patients with truncus arteriosus and complete atrioventricular canal defect who underwent single ventricular palliation. Five patients with truncus arteriosus and complete atrioventricular canal defect managed along the single ventricle palliation pathway were retrospectively reviewed. Demographic, echocardiographic, cardiac catheterization, and perioperative data were analyzed. All patients underwent neonatal palliation tailored to their anatomy (excision of pulmonary arteries from the common trunk and systemic to pulmonary artery shunt in two patients, excision of pulmonary artery and right ventricle to pulmonary artery conduit in two patients, and bilateral branch pulmonary artery bands in one patient). There were two early deaths after neonatal palliation. At a median follow-up of 210 days (interquartile range 1,210 days), all three survivors have undergone second-stage palliation. Of these patients, one is interstage II to III, and two patients have completed their Fontan procedure and are doing well. Truncus arteriosus with complete atrioventricular canal defect is a rare combination of defects. Single ventricle palliation pathway with a tailored neonatal approach may be employed for patients with uncommitted ventricular septal defects.


[Minimally invasive interventions in the treatment of pancreatic diseases].
We have used minimal invasive therapy in the treatment of pancreatic diseases for a long time. CT and/or ultrasound guided techniques have been used for the treatment of pancreatic pseudocysts for more than 20 years. The development of technology has also made an opportunity for the extensive use of laparoscopic surgery at patients suffering from pancreatic diseases. Currently, almost every type of open operation has a laparoscopic version, too. By now we can take part in the combined use of the CT/US and laparoscopic techniques. Recently the new NOTES procedures have appeared. Based on the literary items, the author summarizes the possibilities of minimal invasive treatments in pancreatic diseases.


Comparison of Periodontal Inflammatory Parameters and Whole Salivary Cytokine Profile Among Saudi Patients with Different Obesity Levels.
The aim of the present study was to compare clinical periodontal parameters and salivary interleukin (IL)-1β and IL-6 levels in patients with different obesity levels. A total of 419 individuals with class I, II, and III obesity and nonobese with chronic periodontitis were included. Clinical periodontal parameters were recorded, and whole salivary IL-1β and IL-6 were quantified using enzyme-linked immunosorbent assay. Clinical parameters and salivary cytokine concentrations were analyzed using one-way analysis of variance. For multiple comparisons, Bonferroni post hoc adjustment test was used. Clinical periodontal parameters and salivary IL-1β and IL-6 levels were statistically significant in class II and class III obese as compared to class I obese patients (P < .01) but were comparable between class II and class III obese individuals. These findings should be interpreted with caution due to the inclusion of hyperglycemic patients.


Effort Deficits and Depression: The Influence of Anhedonic Depressive Symptoms on Cardiac Autonomic Activity During a Mental Challenge.
Motivational approaches to depression emphasize the role of dysfunctional motivational dynamics, particularly diminished reward and incentive processes associated with anhedonia. A study examined how anhedonic depressive symptoms, measured continuously across a wide range of severity, influenced the physiological mobilization of effort during a cognitive task. Using motivational intensity theory as a guide, we expected that the diminished incentive value associated with anhedonic depressive symptoms would reduce effort during a "do your best" challenge (also known as an unfixed or self-paced challenge), in which effort is a function of the value of achieving the task's goal. Using impedance cardiography, two cardiac autonomic responses were assessed: pre-ejection period (PEP), a measure of sympathetic activity and our primary measure of interest, and respiratory sinus arrhythmia (RSA), a measure of parasympathetic activity. As expected, PEP slowed from baseline to task as anhedonic depressive symptoms increased (as measured with the DASS Depression scale), indicating diminished effort-related sympathetic activity. No significant effects appeared for RSA. The findings support motivational intensity theory as a translational model of effort processes in depression and clarify some inconsistent effects of depressive symptoms on effort-related physiology found in past work.


Evaluation of the relationship between dermatoglyphics and mandibular third molar impaction: A cross-sectional study.
Background: Dermatoglyphics can be utilised in clinical settings to identify those who are more likely to have impacted teeth. Additionally, dermatoglyphics looks to have potential as a non-invasive diagnostic method for predicting the presence or absence of an impacted tooth. The goal of this study was to look at the most common dermatoglyphic pattern in people who had or didn't have an impacted mandibular third molar teeth and see if there was a dermatoglyphic signature. Methods: A cross-sectional study with 180 participants was conducted (90 cases and 90 controls). The rolling impression technique was used to apply blue duplicating ink to participants' fingertips, which was then recorded. There was an increase in the frequency of the whorl-plain pattern in the right-hand ring finger (60%; p=0.028) and left-hand little finger (33.3%; p=0.009), as well as the loop-ulnar pattern in the right-hand middle finger (74.4%; p=0.024) in individuals with a predisposition to the presence of impacted teeth. Results: The left-hand little finger was found to be the most predictive for impaction in a forward stepwise binary logistic regression analysis. Conclusions: Dermatoglyphics could be used as a non-invasive sign to predict whether or not a tooth is affected. Its value comes in early detection, which helps to avoid the surgical problems that come with symptomatic extraction of an impacted tooth.


Current concepts in the diagnosis and management of poorly differentiated gastrointestinal neuroendocrine carcinomas.
Poorly differentiated neuroendocrine carcinomas (PDNEC) are rare tumours that can originate from any site of the gastrointestinal tract exhibiting an overall aggressive behaviour that may vary between tumours according to the degree of cellular proliferation. The majority of PDNEC are locally advanced or metastatic at presentation, and are only infrequently associated with secretory hormonal syndromes. PDNEC exhibit aggressive histological features (high mitotic rate, high Ki67 labelling index and presence of necrosis) and are further subdivided into two morphological subgroups, small and large cell variants. As PDNEC express somatostatin receptors less frequently, somatostatin receptor scintigraphy is usually negative, whereas 18F-fluorodeoxyglucose positron emission tomography appears to be the best method of evaluating disease spread and guiding further treatment. PDNEC have traditionally been treated similarly to small cell lung carcinoma, although they show a number of different clinical and histopathologic features. First line systemic chemotherapy with a platinum-based agent and etoposide is used for patients with metastatic disease, leading to variable response rates that are often of relative short duration. Sequential or concurrent chemoradiation is recommended for patients with locoregional disease. In patients with localised disease, complete surgical resection should be offered followed by adjuvant treatment (chemotherapy with or without radiotherapy); the value of neoadjuvant chemotherapy has not been evaluated as yet. The role of second line therapies is evolving, with temozolomide being a promising agent. However, the majority of data regarding PDNEC is hampered by the small number of series and their retrospective nature, making it important that multicentre co-operative studies be performed.


Survival status and functional outcome of children who required prolonged intensive care after cardiac surgery.
Children who require prolonged intensive care after cardiac surgery are at risk of high mortality. The long-term survival and functional outcome of these children have not been studied in detail. Children who stayed in intensive care for >28 days after cardiac surgery from 1997 to 2012 were studied in a single institution. A total of 116 patients were identified; 107 (92%) were <1 year of age and 63 (54%) had univentricular physiology. The incidence of children requiring prolonged intensive care increased from 1.01/100 undergoing cardiac surgery in 1997 to 2000 to 2.66/100 in 2009 to 2012 (P trend = .002). This increase coincided with an increase in the number of children with hypoplastic left heart syndrome having prolonged intensive care during the same period (0.13/100 in 1997-2000 to 1.0/100 in 2009-2012; P trend = .001). Survival to pediatric intensive care unit (PICU) discharge was 74% (95% confidence interval [CI], 65-82) and 51% (95% CI, 41-59) at 3 years. Factors associated with mortality were univentricular repair (hazard ratio [HR], 2.12; 95% CI, 1.21-3.70; P = .008) and acute renal failure (HR, 3.01; 95% CI, 1.77-5.12; P < .001), but era did not influence mortality (1997-2005 vs 2006-2012; log-rank P = .66). Among PICU survivors, 3-year survival in those who did not need early reoperation was 81% (95% CI, 66-90), compared with 58% (95% CI, 42-71) in those who required early reoperation (log-rank P = .01). Among survivors, 36% had either moderate or severe disability and 13% had poor quality of life. The incidence of children requiring prolonged intensive care after cardiac surgery has increased in our institution. Our data suggest that the long-term outcome for most of these children is poor, especially after univentricular repair.


Liquid dispensing in the adhesive hairy pads of dock beetles.
Many insects can climb on smooth inverted substrates using adhesive hairy pads on their legs. The hair-surface contact is often mediated by minute volumes of liquid, which form capillary bridges in the contact zones and aid in adhesion. The liquid transport to the contact zones is poorly understood. We investigated the dynamics of liquid secretion in the dock beetle Gastrophysa viridula by quantifying the volume of the deposited liquid footprints during simulated walking experiments. The footprint volume increased with pad-surface contact time and was independent of the non-contact time. Furthermore, the footprint volume decreased to zero after reaching a threshold cumulative volume (approx. 30 fl) in successive steps. This suggests a limited reservoir with low liquid influx. We modelled our results as a fluidic resistive system and estimated the hydraulic resistance of a single attachment hair of the order of MPa · s/fl. The liquid secretion in beetle hairy pads is dominated by passive suction of the liquid during the contact phase. The high calculated resistance of the secretion pathway may originate from the nanosized channels in the hair cuticle. Such nanochannels presumably mediate the transport of cuticular lipids, which are chemically similar to the adhesive liquid.


The Influence of Sprint Mechanical Properties on Change of Direction in Female Futsal Players.
The aim of the present study was to analyze the association of the sprint force-velocity profile [Hzt FV profile] variables with change of direction [COD] performance in female futsal players. Twelve female futsal players (age: 19.83 ± 4.2 years; body height: 160.75 ± 8.37 cm; body mass: 57.64 ± 8.3 kg) volunteered to be evaluated in the following assessments: Hzt FV profile, 505 test, modified 505 test [M505test] and V-cut test. The Spearman's correlation coefficient [rs] (p < 0.05) was used to determine the relationship of the mechanical variables of the sprint (maximum power output [Pmax], maximum horizontal force production [F0] and maximum velocity [V0]) with COD performance. V0 showed a very large significant association with the 505 test (rs = -0.767; 90% CI: (-0.92 to -0.43); p < 0.01) and a large association with the V-cut test (rs = -0.641; 90% CI: (-0.86 to -0.21); p < 0.05), whereas Pmax was strongly associated with results of the 505 test (rs = -0.821; 90% CI: (-0.94 to -0.55); p < 0.01) and largely associated with the V-cut test results (rs = -0.596; 90% CI: (-0.84 to -0.14); p < 0.05). In conclusion, maximal power and velocity output during sprinting are determinant factors to successful COD in 180º and 45º cuts, thus, the Hzt FV profile should be assessed in female futsal players to better understand the influence of sprint mechanical properties on COD performance and prescribe individualized training programs.


Advancements in the Clinical Outcomes of Functional Neurosurgery With Deep Brain Stimulation for Movement Disorders: A Literature Review.
This literature review explores recent advancements in deep brain stimulation (DBS) surgery for movement disorders. It highlights notable improvements, including closed-loop stimulation techniques, optogenetics, and improved surgical targeting. Positive clinical outcomes with low complication rates and improved motor symptoms are consistently reported. The review emphasizes the importance of minimizing risks through meticulous surgical practices and discusses potential complications associated with DBS surgery. Future prospects focus on enhancing technology, refining surgical techniques, and conducting further research. Closed-loop stimulation optimizes DBS efficacy by tailoring stimulation parameters to individual patient needs. Optogenetics offers precise modulation of neural activity with light-sensitive proteins, enabling more targeted treatments. Cybersecurity measures are essential due to the integration of wireless and digital technologies in DBS systems. DBS surgery has significantly improved the management of movement disorders with its safety and effectiveness. Ongoing research in closed-loop stimulation, optogenetics, and cybersecurity is expected to further enhance DBS technology and outcomes, benefiting patients with treatment-resistant movement disorders.


A brief elevation of serum amyloid A is sufficient to increase atherosclerosis.
Serum amyloid A (SAA) has a number of proatherogenic effects including induction of vascular proteoglycans. Chronically elevated SAA was recently shown to increase atherosclerosis in mice. The purpose of this study was to determine whether a brief increase in SAA similarly increased atherosclerosis in a murine model. The recombination activating gene 1-deficient (rag1(-/-)) × apolipoprotein E-deficient (apoe(-/-)) and apoe(-/-) male mice were injected, multiple times or just once respectively, with an adenoviral vector encoding human SAA1 (ad-SAA); the injected mice and controls were maintained on chow for 12-16 weeks. Mice receiving multiple injections of ad-SAA, in which SAA elevation was sustained, had increased atherosclerosis compared with controls. Strikingly, mice receiving only a single injection of ad-SAA, in which SAA was only briefly elevated, also had increased atherosclerosis compared with controls. Using in vitro studies, we demonstrate that SAA treatment leads to increased LDL retention, and that prevention of transforming growth factor beta (TGF-β) signaling prevents SAA-induced increases in LDL retention and SAA-induced increases in vascular biglycan content. We propose that SAA increases atherosclerosis development via induction of TGF-β, increased vascular biglycan content, and increased LDL retention. These data suggest that even short-term inflammation with concomitant increase in SAA may increase the risk of developing CVD.


Association between dietary calcium, potassium, and magnesium consumption and glaucoma.
Calcium (Ca), potassium (K) and magnesium (Mg) may be involved in the occurrence and development of glaucoma by influencing the retinal oxidative stress and regulate blood pressure. However, epidemiological opinions on dietary intake of macroelement related to glaucoma are inconsistent. Herein, this study aims to explore the association between dietary Ca, K, and Mg consumption and glaucoma. Data of 7,042 adults aged ≥40 years old who received the glaucoma examinations were extracted from the National Health and Nutrition Examination Survey (NHANES) database from 2005 to 2008 in this cross-sectional study. Univariate and multivariate logistic regression were used to explore the association between dietary Ca, K, and Mg intake and glaucoma with the odd ratios (ORs) and 95% confidence intervals (CIs). We also investigated this relationship in individuals of different age, with/without hypertension and visual field defect (VFD). There were 502 (8.11%) participants had glaucoma. After adjusted for covariables, we found that enough dietary Ca consumption was related to a decreased risk of glaucoma [OR = 0.59, 95%CI: (0.42-0.81)], whether in persons with/without hypertension (all P<0.05). In particular, dietary K intake may be a potential protect factor for glaucoma in non-hypertension populations [OR = 0.47, 95%CI: (0.22-0.99), P = 0.049]. Additionally, hypertension/non-hypertension persons who aged <65 years old or with/without VFD should all pay attention to the enough dietary supplement of Ca, K, and Mg according to their own circumstances. Enough dietary Ca, K, and Mg consumption may be potential protect factors of glaucoma that could provide some dietary reference for developing targeted glaucoma prevention and control measures.


Changes of cervical sagittal alignments during motions in patients with cervical kyphosis.
Changes of cervical sagittal alignment during motion in cervical kyphosis patients have never been published before. This study was to investigate the changes and provide a better reference for orthopedic treatment.Randomized double-blind repeat trial was carried out on 60 patients with cervical kyphosis. On standard position, hyper flexion, and hyper extension sagittal radiographs, the following measurements were made: the C2-7 vertebral body spatial alignment angle (∠A), C2-7 vertebral lower terminal lamina tilt angle (∠B), C2/3 to C6/7 segmental intervertebral space angle (∠C), the distance from the posterior edge of odontoid to C7 vertebral body (D value), and the difference of angle A, B, and C between cervical flexion and extension movement. Another 60 healthy volunteers were enrolled, of whom the cervical curve apex was determined using Borden's method to compare change and distribution characteristics to patients with cervical kyphosis and C value.In standard lateral position, ∠A was positive and increased from C2 to C7. In hyper extension position, ∠A decreased with reducing amplitude from C2 to C7 compared with the standard position, whereas in hyper flexion position, the average value of ∠A increased with decreasing amplitude from C2 to C7. ∠B followed similar change regularities as ∠A with a larger mean value. In cervical flexion and extension movement, ∠A change of upper vertebral body (∠D) was almost equal to ∠A change of lower vertebral body and ∠C change between the adjacent 2 vertebral bodies (∠E). The curve apex distribution was almost between C4 and C5 in cervical kyphosis patients. A significant difference was observed between cervical kyphosis patients and normal people in C value and D value.The correction of the cervical kyphosis can be carried out from the apex of the cervical spine that provides a solid theoretical foundation for the correction of the cervical kyphosis.


Experimental replacement of the inferior vena cava: factors affecting patency.
To evaluate factors influencing graft patency in the venous system, we replaced the inferior vena cava (IVC) in 50 dogs. Expanded polytetrafluoroethylene ( ePTFE ) grafts with external support were implanted into 32 animals while autogenous, spiral jugular vein grafts were used to replace the IVC in 18 dogs. 111In-labeled autologous platelets and 125I-labeled canine fibrinogen were utilized to evaluate early thrombus formation. A distal arteriovenous (AV) fistula significantly (P less than 0.05) decreased both platelet and fibrin deposition on ePTFE grafts 3 hours following implantation. Patency rate of 12 ePTFE grafts with a temporary AV fistula was higher (75%) than that of grafts without fistula (25%) at 3 months (P less than 0.05). Spiral vein grafts with fistula showed 91% patency at 3 months; without fistula patency was only 67%. Venograms confirmed patency in five grafts followed up to 6 months. Antiplatelet therapy resulted in 100% patency in ePTFE and vein grafts during its administration, and vein grafts maintained patency after discontinuation of antiplatelet treatment. Spiral vein grafts showed no decrease in cross-sectional area at 3 months, while the cross-sectional area of ePTFE grafts decreased significantly (59%). Distal AV fistula decreases platelet and fibrin deposition leading to early occlusion in ePTFE grafts and produces excellent patency in spiral vein grafts. Antiplatelet therapy appears to further improve patency.


[On the history of vectorcardiography: past, present, future].
The vector concept in the analysis of the electrical signals of the heart began to be used at the dawn of the development of electrocardiology. For several decades, vectorcardiography has developed in parallel with electrocardiography; reached its peak in the 60s, and after a period of cooling experienced a resurgence since the early 90s, when it became possible to mathematically synthesize vectorcardiograms (VCG) from digital electrocardiograms in 12 leads. VCG reflects the same phenomena as electrocardiography, but allows you to calculate and visualize a number of three-dimensional characteristics of the electrical signals of the heart. The article describes the main milestones in the development of the VCG, the history of international cooperation in this area, the contribution of domestic scientists to this field of science. Modern promising areas of research related to the vector concept of the analysis of the electrical signals of the heart are briefly reflected.


[Prevention and treatment of thoracic empyema resulting from traumatic hemothorax].
Authors report on their experiences with the treatment of thoracic empyema developing from the suppuration of haematoma following thoracic injury. In 30 of 82 patients suppuration of the thoracic cavity has developed. 6 of the 30 patients with empyema were treated first in our Department all 6 healed on drainage whereas in 24 patients, admitted from other departments, the following measures were necessary: 2 pleura lavages under the control of thoracoscope, 3 early decortications, 14 decortications, 5 lung resections and decortications with a decrease of the respiratory surface. Attention is called to the necessity of early and adequate treatment which is a prevention of complication (suppuration). Light is given to the factors which most frequently promote suppuration of the thoracic cavity, developing from traumatic haemothorax. Attention is called to secure the necessary personal and material conditions to the preventive treatment.


A new leadless pacemaker with atrioventricular synchronous pacing replacing a still working VVI leadless pacemaker: a case report.
A new intracardiac leadless pacemaker (ILP) has been developed to ensure atrioventricular (AV) synchrony (AVS) during ventricular pacing (VP). Recent studies have shown the feasibility and safety of accelerometer-based atrial sensing and an improvement in AVS among patients with atrioventricular block implanted with the Micra AV ILP (Medtronic Inc., Minneapolis, MN, USA). However, no data exists about the benefits of a VDD ILP in patients wearing a still working VVI Nanostim ILP (St Jude Medical, St Paul, MN, USA). We describe the feasibility of the procedure and the absence of device-related adverse events in the short-term follow-up. We present the case of a 72-year-old man implanted with a VVI ILP (Nanostim, St Jude Medical, St Paul, MN, USA) on May 2014, who has developed symptomatic high percentage of VVI asynchronous pacing and was treated with an upgrade to synchronous AV pacemaker (PM) ILP-Micra AV (Medtronic Inc., Minneapolis, MN, USA), which has improved symptoms and functional class. Intracardiac leadless pacemakers represent the best current option for patients requiring PM implantation who are at high risk of infection and bleeding. Our case shows that the new AVS ILP is a good alternative to VVI ILP in patients with sinus rhythm and a strong need for VP.


['I don't want readers': options for treatment of presbyopia].
Presbyopia is farsightedness of old-age. Due to lenticular stiffness, decreased accommodative range, and decreased ciliary muscle function, the ability to see up close diminishes with age. Clinically this means people will need reading glasses. Cataract surgery is the most performed and successful surgery to improve patients' visual acuity. Currently there are many possibilities of solving presbyopia during cataract surgery. This can be achieved by using premium implant lenses, which are lenses that have more than one focus, enabling freedom from spectacles postoperatively. These premium lenses allow vision at the near, intermediate and distance foci, decreasing dependence on optical aids. In this article we will explain the options, and patients' suitability for these solutions and will briefly outline the ins and outs of presbyopia correcting surgery.


Voluntary exercise does not increase gastrointestinal motility but increases spatial memory, intestinal eNOS, Akt levels, and Bifidobacteria abundance in the microbiome.
The interaction between the gut and brain is a great puzzle since it is mediated by very complex mechanisms. Therefore, the possible interactions of the brain-exercise-intestine-microbiome axis were investigated in a control (C, N = 6) and voluntarily exercised (VE, N = 8) middle-aged rats. The endurance capacity was assessed by VO2max on the treadmill, spatial memory by the Morris maze test, gastrointestinal motility by EMG, the microbiome by 16S RNA gene amplicon sequencing, caveolae by electron microscopy, and biochemical assays were used to measure protein levels and production of reactive oxygen species (ROS). Eight weeks of voluntary running increased VO2max, and spatial memory was assessed by the Morris maze test but did not significantly change the motility of the gastrointestinal tract or production of ROS in the intestine. The protein kinase B (Akt) and endothelial nitric oxide synthase (eNOS) protein levels significantly increased in the intestine, while peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1α), mitochondrial transcription factor A (TFAM), nuclear respiratory factor 1 (NFR1), SIRT1, SIRT3, nicotinamide phosphoribosyl transferase (NAMPT), and nuclear factor κB (NF-κB) did not change. On the other hand, voluntary exercise increased the number of caveolae in the smooth muscles of the intestine and relative abundance of Bifidobacteria in the microbiome, which correlated with the Akt levels in the intestine. Voluntary exercise has systemic effects and the relationship between intestinal Akt and the microbiome of the gastrointestinal tract could be an important adaptive response.


Impact of anticipated financial burden on patient decision to undergo contralateral prophylactic mastectomy.
We sought to determine whether patients undergoing contralateral, prophylactic mastectomy have greater anticipated and actual costs and financial burden than patients undergoing unilateral mastectomy, whether these financial considerations influence surgical decision making, and whether this affects satisfaction with surgical decision and overall quality of life. Female patients with unilateral breast cancer who underwent mastectomy at a large academic institution were surveyed regarding their financial experience surrounding the decision whether to undergo contralateral, prophylactic mastectomy. Of 109 patients approached, 101 completed the survey (response rate: 93%); 55 patients (55%) had contralateral, prophylactic mastectomy. Of the respondents, 16% reported that their decision was at least somewhat affected by anticipated costs. More patients opting for contralateral, prophylactic mastectomy had a "very large" anticipated financial burden than unilateral mastectomy patients (26% vs 9%, P = .037), but actual out-of-pocket costs and financial burden were similar between the two groups. Contralateral, prophylactic mastectomy patients, however, did not differ from unilateral mastectomy patients in their satisfaction with their decision nor quality of life, regardless of out-of-pocket costs or financial burden (P > .05). Although contralateral, prophylactic mastectomy patients are more likely to anticipate a "very large" financial burden compared with unilateral mastectomy patients, this does not seem to deter them from the contralateral procedure.


Candidate gene association analyses for ketosis resistance in Holsteins.
High-yielding dairy cattle are susceptible to ketosis, a metabolic disease that negatively affects the health, fertility, and milk production of the cow. Interest in breeding for more robust dairy cattle with improved resistance to disease is global; however, genetic evaluations for ketosis would benefit from the additional information provided by genetic markers. Candidate genes that are proposed to have a biological role in the pathogenesis of ketosis were investigated in silico and a custom panel of 998 putative single nucleotide polymorphism (SNP) markers was developed. The objective of this study was to test the associations of these new markers with deregressed estimated breeding values (EBV) for ketosis. A sample of 653 Canadian Holstein cows that had been previously genotyped with a medium-density SNP chip were regenotyped with the custom panel. The EBV for ketosis in first and later lactations were obtained for each animal and deregressed for use as pseudo-phenotypes for association analyses. Results of the mixed inheritance model for single SNP association analyses suggested 15 markers in 6 unique candidate genes were associated with the studied trait. Genes encoding proteins involved in metabolic processes, including the synthesis and degradation of fatty acids and ketone bodies, gluconeogenesis, lipid mobilization, and the citric acid cycle, were identified to contain SNP associated with ketosis resistance. This work confirmed the presence of previously described quantitative trait loci for dairy cattle, suggested novel markers for ketosis-resistance, and provided insight into the underlying biology of this disease.


Nanomedicine strategies for hematological malignancies: what is next?
The major obstacle in treating cancer depends on the low therapeutic index of most anticancer drugs. The lack of specificity, coupled with the large volumes of distribution, translates into a nonpreferential distribution of anticancer drugs to the tumor. Accordingly, the dose of the anticancer drug that is achievable within tumor is limited, resulting in suboptimal treatment and unwanted toxicity. Nanoparticles applied as drug-delivery systems are submicron-sized (3-200 nm) particles, that can enhance the selectivity of the active drug to cancer cells through a change of its pharmacokinetic profile, while avoiding toxicity in normal cells. This review will discuss the current uses of nanodrugs in hematology, with a focus on the most promising nanoparticles in development for the treatment of hematologic tumors.