Inhibitors of NLRP3 Inflammasome in Ischemic Heart Disease: Focus on Functional and Redox Aspects.
Myocardial ischemia-reperfusion injury (MIRI) is caused by several mechanisms, including the production of reactive oxygen species (ROS), altered cellular osmolarity, and inflammatory response. Calcium overload, altered oxygen levels, and mitochondrial ROS are also involved in these MIRI processes, resulting in the irreversible opening of the mitochondrial permeability transition pore (mPTP). These mechanisms and processes are associated with NLRP3 inflammasome priming and activation, which can also induce cell death by pyroptosis through the up-regulation of the caspase-1 pathway and IL-18 release. In addition, endothelial dysfunction, both in the presence and absence of MIRI, is also accompanied by altered oxygen levels, decreased nitric oxide production, and ROS overproduction, resulting in the expression of adhesion molecules and leukocyte infiltration in which the NLRP3 inflammasome plays a central role, thus contributing, through endothelial dysfunction, to the alteration of coronary flow, typical of ischemic heart disease. Given the intricate interrelationship between ROS and NLRP3, ROS inhibitors can reduce NLRP3 inflammasome activation, while NLRP3 inhibitors can reduce oxidative stress and inflammation. NLRP3 inhibitors have been intensively studied as anti-inflammatory agents in basic cardiovascular sciences. In this review, we analyze the interrelation between ROS and NLRP3 in ischemic heart disease and the effects of some NLRP3 inhibitors as possible therapeutic agents in this disease condition. All compounds considered in this review need larger studies to confirm their appropriate use in clinical scenarios as anti-ischemic drugs.


Inositol regulates phosphatidylglycerolphosphate synthase expression in Saccharomyces cerevisiae.
The enzyme phosphatidylglycerolphosphate synthase (PGPS; CDPdiacylglycerol-glycerol-3-phosphate 3-phosphatidyltransferase; EC 184.108.40.206) catalyzes the committed step in the synthesis of cardiolipin, a phospholipid found predominantly in the mitochondrial inner membrane. To determine whether PGPS is regulated by cross-pathway control, we analyzed PGPS expression under conditions in which the regulation of general phospholipid synthesis could be examined. The addition of inositol resulted in a three- to fivefold reduction in PGPS expression in wild-type cells in the presence or absence of exogenous choline. The reduction in enzyme activity in response to inositol was seen in minutes, suggesting that inactivation or degradation of the enzyme plays an important role in inositol-mediated repression of PGPS. In cho2 and opi3 mutants, which are blocked in phosphatidylcholine synthesis, inositol-mediated repression of PGPS did not occur unless choline was added to the media. Three previously identified genes that regulate general phospholipid synthesis, INO2, INO4, and OP11, did not affect PGPS expression. Thus, ino2 and ino4 mutants, which are unable to derepress biosynthetic enzymes involved in general phospholipid synthesis, expressed wild-type levels of PGPS activity under derepressing conditions. PGPS expression in the opi1 mutant, which exhibits constitutive synthesis of general phospholipid biosynthetic enzymes, was fully repressed in the presence of inositol and partially repressed even in the absence of inositol. These results demonstrate for the first time that an enzymatic step in cardiolipin synthesis is coordinately controlled with general phospholipid synthesis but that this control is not mediated by the same genetic regulatory circuit.


Detecting switching and intermittent causalities in time series.
During the last decade, complex network representations have emerged as a powerful instrument for describing the cross-talk between different brain regions both at rest and as subjects are carrying out cognitive tasks, in healthy brains and neurological pathologies. The transient nature of such cross-talk has nevertheless by and large been neglected, mainly due to the inherent limitations of some metrics, e.g., causality ones, which require a long time series in order to yield statistically significant results. Here, we present a methodology to account for intermittent causal coupling in neural activity, based on the identification of non-overlapping windows within the original time series in which the causality is strongest. The result is a less coarse-grained assessment of the time-varying properties of brain interactions, which can be used to create a high temporal resolution time-varying network. We apply the proposed methodology to the analysis of the brain activity of control subjects and alcoholic patients performing an image recognition task. Our results show that short-lived, intermittent, local-scale causality is better at discriminating both groups than global network metrics. These results highlight the importance of the transient nature of brain activity, at least under some pathological conditions.


Chemical structures of manure from conventional and phytase transgenic pigs investigated by advanced solid-state NMR spectroscopy.
Nonpoint phosphorus (P) pollution from animal manure is becoming a serious global problem. The current solution for the swine industry includes the enzyme phytase as a component in oil meal and cereal grain-based swine diets. A long-term approach is the production of transgenic phytase pigs that express phytase in the salivary glands and secrete it in the saliva. This study provides a detailed comparison of chemical structures of manure from conventional pigs and transgenic pigs that express phytase under growing and finishing phases using new solid-state NMR techniques. Spectral editing techniques and quantitative NMR techniques were used to identify and quantify specific functional groups. Two-dimensional (1)H- (13)C heteronuclear correlation NMR was used to detect their connectivity. Manure from conventional and transgenic pigs had similar peptide, carbohydrate, and fatty acid components, while those from transgenic pigs contained more carbohydrates and fewer nonpolar alkyls. There was no consistent effect from diets with or without supplemental phosphate or growth stages.


Testing cognitive functions in rodent disease models: Present pitfalls and future perspectives.
Testing of cognitive functions in rodent disease models constitutes a substantial sector of behavioral neuroscience. It is most often needed in phenotyping genetically modified new rodent (usually mouse) lines or in preclinical testing of cognitive effects of new CNS drugs. This review concerns present pitfalls and future perspectives in this large field, with an emphasis on memory testing in CNS disease models and their preclinical drug testing. It is important to realize that no behavioral test is specific for a single cognitive domain. There are numerous noncognitive factors that may lead to impaired performance in most widely applied memory tasks. It is important to rule these out by applying a battery of test that should include at least tests for motor functions, spontaneous activity and anxiety besides cognitive aspects. In addition, considering and reporting all task-relavant details will help to resolve the common problem that certain behavioral findings cannot be reproduced by other laboratories. More collaboration between molecular and behavioral neuroscience laboratories and systematic training of young neuroscientist on behavioral techniques will help ensure quality of behavioral studies in the future.


Longitudinal analysis of endemic gentamicin- and tobramycin-resistant gram-negative bacilli in a community hospital.
The epidemiology of endemic gentamicin- and tobramycin-resistant gram-negative bacilli at a community hospital was analyzed over a one-year period three years following an original analysis at the same hospital. The frequency and distribution of resistant organisms remained stable over the time spanning the two studies. Only 2.8% of all gram-negative bacilli were resistant to gentamicin or tobramycin, and the majority of resistant isolates were non-Enterobacteriaceae. The respiratory and urinary tracts remained the body sites most prone to harbor resistant organisms. Risk analysis using a matched comparison group again revealed prior treatment with an aminoglycoside to be the only significant factor pre-disposing to acquisition of resistant gram-negative bacilli. This analysis indicates that community hospitals may not be important reservoirs of endemic aminoglycoside-resistant gram-negative bacilli, and reconfirms the observation that each hospital must define its own pattern of aminoglycoside resistance and unique risk factors.


Use of antidepressants in late-life depression.
Late-life depression (LLD) is a common and typically recurrent illness that is often unrecognized and under-treated. It is associated with significant co-morbidities and poor health outcomes. Antidepressants are typically used as a first-line treatment for LLD. We performed a systematic review of the English literature (1996 to August 2007) and present results relevant to the efficacy of antidepressants in acute and maintenance pharmacotherapy of LLD, the predictors of LLD treatment outcomes and pharmacological strategies for non-remission. There is a consensus in the literature that the goal of treatment should be remission. Although antidepressants can be categorized into several classes based on their putative mechanisms of action, there is no consistent evidence that antidepressants from different classes are associated with different rates of remission of LLD. After achieving remission, the evidence supports a beneficial role of maintenance pharmacotherapy in reducing the rate of recurrence of LLD for at least 2 years. There are reports of a number of possible augmentation and switching strategies that can be used when LLD remission is not attained. However, none of these various strategies has been studied rigorously in patients with LLD as yet. Overall, the current literature is adequate for guiding acute and maintenance pharmacotherapy of LLD but further research is urgently needed to guide clinical strategies in non-remission.


Gene-diet interactions in gastric cancer risk: a systematic review.
To conduct a systematic review of the published epidemiological studies investigating the association of the interactions between gene variants and dietary intake with gastric cancer risk. A literature search was conducted in PubMed, EMBASE, and MEDLINE for articles published between January 2000 and July 2013, and 38 studies were identified. Previous studies included various dietary factors (e.g., fruits and vegetables, soybean products, salt, meat, and alcohol) and genetic variants that are involved in various metabolic pathways. Studies suggest that individuals who carry high-risk genetic variants and demonstrate particular dietary habits may have an increased risk of gastric cancer compared with those who do not carry high-risk genetic variants. Distinctive dietary patterns and variations in the frequency of genetic variants may explain the higher incidence of gastric cancer in a particular region. However, most previous studies have limitations, such as a small sample size and a retrospective case-control design. In addition, past studies have been unable to elucidate the specific mechanism in gene-diet interaction associated with gastric carcinogenesis. Additional large prospective epidemiological and experimental studies are required to identify the gene-diet metabolic pathways related to gastric cancer susceptibility.


MouseTracker: software for studying real-time mental processing using a computer mouse-tracking method.
In the present article, we present a software package, MouseTracker, that allows researchers to use a computer mouse-tracking method for assessing real-time processing in psychological tasks. By recording the streaming x-, y-coordinates of the computer mouse while participants move the mouse into one of multiple response alternatives, motor dynamics of the hand can reveal the time course of mental processes. MouseTracker provides researchers with fine-grained information about the real-time evolution of participant responses by sampling 60-75 times/sec the online competition between multiple response alternatives. MouseTracker allows researchers to develop and run experiments and subsequently analyze mouse trajectories in a user-interactive, graphics-based environment. Experiments may incorporate images, letter strings, and sounds. Mouse trajectories can be processed, averaged, visualized, and explored, and measures of spatial attraction/curvature, complexity, velocity, and acceleration can be computed. We describe the software and the method, and we provide details on mouse trajectory analysis. We validate the software by demonstrating the accuracy and reliability of its trajectory and reaction time data. The latest version of MouseTracker is freely available at http://mousetracker.jbfreeman.net.


Shifts in Community Benefits Spending Among Nonprofit Hospitals in Nebraska and 10 Proximate States, 2012 and 2015.
Federal and state policy makers have debated the evolving concept of community benefit and the extent to which nonprofit hospitals are providing benefits to the community in exchange for the tax benefits they receive. This study compares community benefits spending by nonprofit hospitals in Nebraska and other selected states in both 2012 and 2015. Expenditures are also examined by rural, regional, and urban hospitals within Nebraska. Community benefit expenditure data were taken from Community Benefit Insight and consolidated into the categories of direct patient care, community health improvement initiatives, and health professions education and research. When community benefit expenditures were compared across 11 states, Nebraska had the highest percentage of expenditures for community health improvement initiatives in both 2012 and 2015. Although community benefit expenditures for the 44 nonprofit hospitals within Nebraska increased from 2012 to 2015, they remained flat as a share of total hospital expenditures. In 2015, 63% of community benefit expenditures were allocated to direct patient care, which represented a 7.3% decrease from 2012. This decline led to greater spending on community health improvement initiatives (3.1%) and health professions education and research (4.2%). Rural, regional, and urban hospitals spent more proportionately on community health improvement initiatives in 2015 than in 2012. The shift in community benefit expenditures from direct patient care to community health improvement initiatives and health professions education and research suggests that hospitals are investing in programs with broader community-wide benefits. Nebraska allocates a significantly larger share of its community benefits spending to community health improvement activities than other Great Plains and Midwestern states. Nebraska is in the process of implementing Medicaid expansion, which may shift future community benefits spending decisions.


[Computer tomographic findings in destructive sternal lesions].
Computer tomographic findings in 25 patients with destructive lesions of the sternum have been analysed. In 14 cases there was, in addition to bone destruction, extensive or ill-defined soft tissue infiltration. With two exceptions. CT demonstrated the bone changes more clearly than conventional tomography. The value of CT lies in its ability to demonstrate the exact extent of the bone destruction with simultaneous demonstration, or exclusion, of soft tissue infiltration. This is of value when resection or radiotherapy is planned.


Protective value of diphenylhydantoin and vitamin A against stress ulcer.
The protective effect of vitamin A and diphenylhydantoin on restraint ulcers has been studied in 105 rats. The Sprague-Dawley female rats were divided into four groups. All were fasted for 24 hours, then restrained and fasted for another 24 hours. Control rats (receiving 1 ml of 0.9% saline solution) were compared with groups receiving either vitamin A, diphenylhydantoin, or both. Diphenylhydantoin significantly (P less than 0.001) protected the rats against ulcers. Vitamin A showed no protective effect and did not potentiate the effect of diphenylhydantoin.


Severe maternal morbidity surveillance: Monitoring pregnant women at high risk for prolonged hospitalisation and death.
There is no international consensus on the definition and components of severe maternal morbidity (SMM). To propose a comprehensive definition of SMM, to create an empirically justified list of SMM types and subtypes, and to use this to examine SMM in Canada. Severe maternal morbidity was defined as a set of heterogeneous maternal conditions known to be associated with severe illness and with prolonged hospitalisation or high case fatality. Candidate SMM types/subtypes were evaluated using information on all hospital deliveries in Canada (excluding Quebec), 2006-2015. SMM rates for 2012-2016 were quantified as a composite and as SMM types/subtypes. Rate ratios and population attributable fractions (PAF) associated with overall and specific SMM types/subtypes were estimated in relation to length of hospital stay (LOS > 7 days) and case fatality. There were 22 799 cases of SMM subtypes (among 1 418 545 deliveries) that were associated with a prolonged LOS or high case fatality. Between 2012 and 2016, the composite SMM rate was 16.1 (95% confidence interval [CI] 15.9, 16.3) per 1000 deliveries. Severe pre-eclampsia and HELLP syndrome (514.6 per 100 000 deliveries), and severe postpartum haemorrhage (433.2 per 100 000 deliveries) were the most common SMM types, while case fatality rates among SMM subtypes were highest among women who had cardiac arrest and resuscitation (241.1 per 1000), hepatic failure (147.1 per 1000), dialysis (67.6 per 1000), and cerebrovascular accident/stroke (51.0 per 1000). The PAF for prolonged hospital stay related to SMM was 17.8% (95% CI 17.3, 18.3), while the PAF for maternal death associated with SMM was 88.0% (95% CI 74.6, 94.4). The proposed definition of SMM and associated list of SMM subtypes could be used for standardised SMM surveillance, with rate ratios and PAFs associated with specific SMM types/subtypes serving to inform clinical practice and public health policy.


Coevolutionary particle swarm optimization using AIS and its application in multiparameter estimation of PMSM.
In this paper, a coevolutionary particle-swarmoptimization (PSO) algorithm associating with the artificial immune principle is proposed. In the proposed algorithm, the wholepopulation is divided into two kinds of subpopulations consisting of one elite subpopulation and several normal subpopulations. The best individual of each normal subpopulation will be memorized into the elite subpopulation during the evolution process. A hybrid method, which creates new individuals by using three different operators, is presented to ensure the diversity of all the subpopulations. Furthermore, a simple adaptive wavelet learning operator is utilized for accelerating the convergence speed of the pbest particles. The improved immune-clonal-selection operator is employed for optimizing the elite subpopulation, while the migration scheme is employed for the information exchange between elite subpopulation and normal subpopulations. The performance of the proposed algorithm is verified by testing on a suite of standard benchmark functions, which shows faster convergence and global search ability. Its performance is further evaluated by its application to multiparameter estimation of permanentmagnet synchronous machines, which shows that its performance significantly outperforms existing PSOs. The proposed algorithm can estimate the machine dq-axis inductances, stator winding resistance, and rotor flux linkage simultaneously.


Communication before coherence.
The hypothesis of communication through coherence proposes that coherent or synchronous oscillations in connected neural systems can promote communication. It has been applied mainly to how oscillations interact in connected networks. We tested by simulations whether information transmission about an external stimulus from one network to a second network is influenced by gamma oscillations, by whether the oscillations are coherent, and by their phase. Gamma oscillations were induced by increasing the relative conductance of AMPA to NMDA excitatory synapses. It was found that small associative connection strengths between the networks were sufficient to produce information transmission (measured by Shannon mutual information) such that the second attractor network took the correct decision based on the state of the first network. Although gamma oscillations were present in both networks, the synaptic connections sufficient for perfect information transmission about the stimulus presented to the network (100% correct, 1 bit of information) were insufficiently strong to produce coherence, or phase-locking, between the two networks; this only occurred when the synaptic strengths between the networks were increased by > 10 ×. Further, the phase of the oscillations between the networks did not influence the information transmission or its speed at these connection strengths. Moreover, information transmission was as good when the AMPA-to-NMDA ratio was reduced to its normal value, and oscillations were not present. Similar results were found when the second network was not an attractor decision-making network. Thus information transmission can occur before synapses have been made sufficiently strong to produce coherence.


Allergen challenge increases cell traffic between bone marrow and lung.
Increases in inflammatory-cell progenitors have been demonstrated in the bone marrow (BM) after inhalation of Ascaris suum in dogs at the time of allergen-induced airway hyperresponsiveness (AHR). The aim of this study was to evaluate the effect of allergen challenge on trafficking of inflammatory cells and their progenitors from the BM to the lung, using a marker of proliferating cells, bromodeoxyuridine (BrdU). BrdU is a thymidine analogue taken up by the DNA of dividing cells, and can be detected with immunohistochemistry (IHC). The development of AHR was assessed through acetylcholine (ACh) airway responsiveness before and after allergen inhalation. Two groups of dogs were matched for the degree of AHR after a screening allergen challenge. On the study day, one group inhaled allergen (n = 8) and one group inhaled diluent (n = 8). All dogs received equal bolus injections of BrdU before and at 5 h after challenge. Blood samples were taken before challenge and at 5 h and 24 h after challenge, and BM aspirate and bronchoalveolar lavage (BAL) samples were taken 24 h after challenge. BrdU-positive cells were detected in cytospin preparations of these samples, using IHC. Allergen inhalation caused AHR (P < 0.05) at 24 h after allergen challenge, and also an increase in BrdU-positive cells in blood, which was 5.7 +/- 0.6% (mean +/- SEM) after allergen challenge and 2.5 +/- 0.7% after diluent (P < 0.005); in BM the increase in BrdU-positive cells was 27.0 +/- 3.4% after allergen challenge and 18.9 +/- 3.2% after diluent (P = 0.1); and in BAL the increase was 3.2 +/- 0.4% after allergen challenge and 0.8 +/- 0.3% after diluent (P < 0.005). There was a significant correlation between the number of BAL neutrophils and the percentage of BrdU-positive BAL cells (r2 = 0.54, P < 0.05). These results demonstrate an allergen-induced increase in proliferating cells, probably in the BM, and indicate that such cells traffic through the circulation into the lungs in response to allergen inhalation.


Schizotypal traits and psychotic-like experiences during adolescence: An update.
The psychosis phenotype is distributed along a severity continuum that ranges from psychological well-being to full-blown psychosis. Schizotypal traits and psychotic-like experiences are considered as one of the possible phenotypic indicators of the latent liability for psychosis (named schizotypy). This selective review offers a general overview and update of trait schizotypy and psychotic like experiences during adolescence. The previous literature on schizotypal traits  and psychotic like experiences is selectively reviewed. We begin with a brief introduction of psychosis syndrome from an extended psychosis phenotype framework as well as a brief definition of trait schizotypy and psychotic-like experiences. We introduce the study of these traits and experiences from a developmental perspective, where the psychosis proneness-persistence-impairment model is highlighted. We provide a selective review of the tools available for assessment these constructs from the psychometric high-risk paradigm. We then discuss the factorial validity of the studies conducted in adolescents. In addition, the links between this set of subclinical traits and experiences and other variables gathered from a translational approach are discussed, with the aim to establish a nomological network. We conclude by considering remaining questions and future directions for the understanding of trait schizotypy and psychotic-like experiences during adolescence.


Impact of organ malperfusion on mortality and morbidity in acute type A aortic dissections.
Organ malperfusion is a serious complication of acute type A aortic dissection. Management and outcome of malperfusion has been discussed in this study. Between November 1994 and May 2003, 118 patients with acute type A aortic dissections were operated. Fifty-seven patients (48.3%) were complicated with organ malperfusion, which is considered as group I. Seventy-three ischemic events were seen in 57 patients with organ malperfusion. Patients in group I were divided into four subgroups according to affected organ system including limb (38 events), coronary (9 events), renal (2 events), visceral (9 events), and cerebral (15 events) ischemia. Sixty-one patients without organ malperfusion constitute group II. The hospital mortality rate was 42.1% (24 of 57) in patients with malperfusion, 14.75% (9 of 61) in group II (p = 0.001), and 27.9% (33 of 118) in all patients. Postoperative complications such as mediastinal hemorrhage, low cardiac output, gastrointestinal system complications, acute renal failure, and multiple organ failure were higher in group I. Mesenteric and limb ischemia associated with high mortality. Multivariate analysis reveals that visceral malperfusion is the strongest predictor of postoperative mortality (odds ratio: 25.09, p = 0.000). Isolated coronary malperfusion had the lowest mortality (one patient, 16.6%) among the patients with organ malperfusion. Acute type A aortic dissections with organ malperfusion has higher postoperative mortality and morbidity. Immediate aortic repair is our management strategy in patients with limb, coronary, and neurological malperfusion. To reduce the extremely high mortality with mesenteric malperfusion, new strategies should be investigated such as surgical delay with interventional procedures.


Vocal Characteristics of Infants at Risk for Speech Motor Involvement: A Scoping Review.
The purpose of this scoping review was to (a) summarize methodological characteristics of studies examining vocal characteristics of infants at high risk for neurological speech motor involvement and (b) report the state of the high-quality evidence on vocal characteristic trends of infants diagnosed or at high risk for cerebral palsy (CP). The PRISMA (Preferred Reporting Items of Systematic Reviews and Meta-Analyses) extension for scoping reviews was followed for reporting our review. Studies measured prelinguistic vocal characteristics of infants under 24 months with birth risk or genetic conditions known to commonly present with speech motor involvement. Fifty-five studies met criteria for Part 1. Eleven studies met criteria for synthesis in Part 2. A smaller percentage of studies examined infants with or at risk for CP compared to studies examining genetic conditions such as Down syndrome. The median year of publication was 1999, with a median sample size of nine participants. Most studies were conducted in laboratory settings and used human coding of vocalizations produced during caregiver-child interactions. Substantial methodological differences were noted across all studies. A small number of high-quality studies of infants with or at risk for CP revealed high rates of marginal babbling, low rates of canonical babbling, and limited consonant diversity under 24 months. Mixed findings were noted across studies of general birth risk factors. There is limited evidence available to support the early detection of speech motor involvement. Large methodological differences currently impact the ability to synthesize findings across studies. There is a critical need to conduct longitudinal research with larger sample sizes and advanced, modern technologies to detect vocal precursors of speech impairment to support the accurate diagnosis and prognosis of speech development in infants with CP and other clinical populations.


[The Father's Role in the Coparenting Partnership.].
The father's role in the coparenting partnership is reviewed from an evolutionary and family systems perspective. Whenever two individuals are available to parent a child, a coparenting relationship exists. The coparenting relationship is developed within the framework of the mother-child attachment relationship. The father's entrance into this system tends to be determined by individual characteristics of the father, which set a baseline level of the father's motivation to parent, and by maternal gatekeeping proclivities, which discourage or facilitate paternal involvement. Three approaches to the coparenting relationship are presented : multidimensional assessments of the division of labor, the parenting alliance, and coparenting interactions. Father's relationships within different family subsystems appear to be less differentiated than those of mothers, leaving coparenting partnerships vulnerable to father's satisfaction with family and marital relationships. The father's commitment to family and the mother's ability to allow fathers some autonomy in parenting are critical factors in coparenting relationships.


Whole-genome sequencing reveals changes in genomic diversity and distinctive repertoires of T3SS and T6SS effector candidates in Chilean clinical Campylobacter strains.
Campylobacter is the leading cause of bacterial gastroenteritis worldwide and an emerging and neglected pathogen in South America. This zoonotic pathogen colonizes the gastrointestinal tract of a wide range of mammals and birds, with poultry as the most important reservoir for human infections. Apart from its high morbidity rates, the emergence of resistant strains is of global concern. The aims of this work were to determine genetic diversity, presence of antimicrobial resistance determinants and virulence potential of Campylobacter spp. isolated from patients with acute gastrointestinal disease at 'Clinica Alemana', Santiago de Chile. The study considered the isolation of Campylobacter spp., from stool samples during a 20-month period (January 2020 to September 2021). We sequenced (NextSeq, Illumina) and performed an in-depth analysis of the genome sequences of 88 Campylobacter jejuni and 2 Campylobacter coli strains isolated from clinical samples in Chile. We identified a high genetic diversity among C. jejuni strains and the emergence of prevalent clonal complexes, which were not identified in our previous reports. While ~40% of strains harbored a mutation in the gyrA gene associated with fluoroquinolone resistance, no macrolide-resistance determinants were detected. Interestingly, gene clusters encoding virulence factors such as the T6SS or genes associated with long-term sequelae such as Guillain-Barré syndrome showed lineage-relatedness. In addition, our analysis revealed a high degree of variability regarding the presence of fT3SS and T6SS effector proteins in comparison to type strains 81-176, F38011, and NCTC 11168 and 488. Our study provides important insights into the molecular epidemiology of this emerging foodborne pathogen. In addition, the differences observed regarding the repertoire of fT3SS and T6SS effector proteins could have an impact on the pathogenic potential and transmissibility of these Latin American isolates, posing another challenge in characterizing the infection dynamics of this emergent and neglected bacterial pathogen.


Comparison of incidence of bloodstream infection with methicillin-resistant Staphylococcus aureus between England and United States, 2006-2007.
We compared incidence of methicillin-resistant Staphylococcus aureus (MRSA) bloodstream infection (BSI) in the United States and England by using population-based surveillance. The incidence of community-onset MRSA BSI was 6.3-fold higher in the United States than in England, whereas the incidence of hospital-onset MRSA BSI was similar between the 2 countries.


Irradiation of rat tubule epithelial cells alters the expression of gene products associated with the synthesis and degradation of extracellular matrix.
To determine the ability of radiation to modulate kidney tubule epithelial cell expression of various molecules involved in regulating extracellular matrix accumulation (collagen types I and III, fibronectin, plasminogen activator-inhibitor 1 (PAI-1), TGF-beta and tissue inhibitor of metalloproteinases-2 (TIMP-2)) and degradation (plasminogen activators u-PA or t-PA, MMP-2 and MMP-9). NRK52E rat tubule epithelial cells were placed in serum-free medium 24 h prior to irradiation with single doses of 1.0-10.0 Gy 137Cs gamma-rays. After irradiation, cells were maintained in serum-free medium for up to 48 h. Irradiation of NRK52E cells was associated with significant dose-dependent increases in collagen I (p<0.05) and PAI-1 (p< or =0.002) mRNA. Collagen III mRNA levels also exhibited a dose-dependent increase; however, this increase failed to reach levels that were statistically significant. Fibronectin mRNA levels were unaltered following irradiation. Radiation also led to an isoform-specific alteration in TGF-beta expression; TGF-beta1 mRNA increased, TGF-beta3 mRNA decreased. The amount of TGF-beta protein secreted into the medium was unchanged following irradiation; however, there was a fivefold increase in the relative amount of active TGF-beta. Irradiation was also associated with differential changes in MMP expression: active MMP-2 levels increased, while MMP-9 levels were unaltered; PA secretion into the medium was unchanged following irradiation. Irradiation of rat kidney tubule epithelial cells leads to altered production of various molecules associated with extracellular matrix accumulation and degradation.


Pulmonary embolism.
Pulmonary embolism is a common and often fatal postoperative complication. Dyspnea is the most common clinical manifestation in pulmonary embolism, and other signs are frequently inconsistent and often vague. The chest film and electrocardiogram may be helpful in excluding other cardiorespiratory diseases but they are frequently unreliable in establishing an objective diagnosis of pulmonary embolism. Documentation of a decreased arterial saturation provides suggestive evidence of pulmonary embolism. Lung scanning is a safe, sensitive procedure for the initial evaluation of symtoms suggestive of pulmonary embolism, and pulmonary arteriography may be necessary to confirm the diagnosis in certain patients. Anticoagulation is effective in the prevention and treatment of pulmonary embolism and proves successful in the vast majority of patients. Emboli that are not fatal gradually resolve in the pulmonary circulation. Vena caval interruption is occasionally beneficial in selected patients, especially those with septic emboli and cor pulmonale, but should only be performed when the indications are quite clear. Under certain selected circumstances pulmonary embolectomy may be indicated. Patients with massive embolism occluding more than one-half of the pulmonary arterial system and prooducing a markedly elevated pulmonary arterial pressure and severe hypoxemia may die in acute right heart failure. Intractable shock unresponsive to aggressive medical therapy in these patients represents an indication for pulmonary embolectomy. The hazards of these surgical procedures demand that a definite diagnosis of pulmonary embolism be made and a systematic approach to the diagnosis and treatment should be followed in all patients with the disorder.


Crystal structures of influenza A virus matrix protein M1: variations on a theme.
Matrix protein 1 (M1) of the influenza A virus plays multiple roles in virion assembly and infection. Interest in the pH dependence of M1's multiple functions led us to study the effect of subtle pH changes on M1 structure, resulting in the elucidation of a unique low-pH crystal structure of the N(1-165)-domain of A/WSN/33 (H1N1) M1 that has never been reported. Although the 2.2 Å crystal structure of M1 N-terminus shows a dimer with the two monomers interacting in a face-to-face fashion at low pH as observed earlier, a 44° rotation of the second monomer has led to a significantly different dimer interface that possibly affects dimer stability. More importantly, while one of the monomers is fully defined, the N-terminal half of the second monomer shows considerable disorder that appears inherent in the protein and is potentially physiologically relevant. Such disorder has not been observed in any other previously reported structure at either low or high pH conditions, despite similar crystallization pH conditions. By comparing our novel N(1-165)-domain structure with other low-pH or neutral-pH M1 structures, it appears that M1 can energetically access different monomer and dimer conformations, as well as oligomeric states, with varying degree of similarities. The study reported here provides further insights into M1 oligomerization that may be essential for viral propagation and infectivity.


Diagnostic and therapeutic utility of transrectal ultrasound in urological office prostatic abscess management: a short report from a single urologic center.
Prostatic abscess (PA) is an infrequent condition in the modern antibiotic era. The everyday use of transrectal ultrasound (TRUS) during diagnostic work-up and the widespread recurrence to prostatic biopsies may lead to an increase of PA diagnosis. In this short report we analyze the patients characteristics and the management of seven recent cases of PA diagnosed in our institution. The records of 7 patients admitted to our Center for LUTS associated to septic fever or acute urinary retention, was prospectively collected. Suspect of PA was done on digital rectal examination (DRE) and confirmed by TRUS performed after urinary system ultrasound (UUS) evaluation. Patients were admitted to hospital only in case of septic signs. A sovrapubic (SPC) or urethral catheter (UC) was placed depending on symptoms. A TRUS-guided aspiration of PA was performed with patient in lithotomic position, using a 18 gauge two-part needle, side/end fire needle access. Patient was discharged with antibiotic therapy and followed up until complete resolution of the PA and symptoms. Mean age was 62 years (range 24-82). Two patients were diabetics and one was affected by the immunodeficiency acquired syndrome (HIV). In one case, PA was detected after a persistent fever post TRUS guided prostate biopsy. Average prostate volume was 69 ml (range 19-118 ml). DRE was able to diagnose PA only in 2 cases (29%), UUS evaluation in 1 case (14%). All cases were confirmed by TRUS as hypo-anechoic areas with or without internal echoes in all patients. Mean PA dimension was 3.64 cm (range 1.5-8). SPC was placed in 3 cases (43%), UC in 3 patients (43%). Only 1 patient refused catheterization. Side fire needle aspiration was performed in all cases and in combination with end fire access in case of particular location of abscess cavities. Second look was needed in 2 cases (29%). Antibiotics were administered in all cases. The aspirated pus showed a positive culture for Escherichia coli (43%), Klebsiella pneumoniae (29%), Pseudomonas aeruginosa (14%) and Enterococcus faecalis (14%). PA resolution time mean was 9 days (range 3-24). TRUS evaluation in case of persistent LUTS associated with fever or acute urinary retention is determinant in the diagnosis of PA. Office or institutional management with TRUS needle aspiration is a good option in these cases.


[Development of the role of an Advanced Practice Nurse in the long-term care of elderly people in Switzerland].
Due to the imminent demographic surge of older people, many suffering from multiple chronic diseases and age-related health problems, the demand for professional nursing care will increase massively over the coming decades. However, the demand for qualified nursing personnel in long-term healthcare is already outpacing the supply. Without a change of course, this can only lead to a crisis of quality. Experiences, e.g. from the U.S., have shown that masters-prepared Advanced Practice Nurses (APN) facilitate quality improvement in the long-term care of elderly people. With their focus on interdisciplinary collaboration and clinical results, they support the development of the institutions they work with and of gerontological nursing in general. This article describes the development of Advanced Nursing Practice in three gerontological long-term care facilities in Switzerland's German speaking region on the basis of practice development projects advancing the assessment and management of pain. APNs' defined competencies serve as a framework to evaluate the implementation of their roles: working in clinical leadership projects, they support interdisciplinary collaboration, focusing on direct clinical practice, the development of evidence-based nursing care, and the expert guidance of nurses. The role of APN in stationary long-term care in Switzerland has considerable potential for development.


0.3% energy stability, 100-millijoule-class, Ti:sapphire chirped-pulse eight-pass amplification system.
Highly stable operation of a two-stage multipass Ti:sapphire amplifier (a four-pass pre-amplifier and a four-pass power amplifier) for a 100-mJ-class chirped-pulse amplification system has been demonstrated by passive stabilization. By optimizing the ratio of pump energies to the two amplifiers and the optical losses artificially inserted into the second power amplifier, a root-mean-square fluctuation in pulse energy of 0.3% was achieved, which was 5 times lower than that of the pump laser. This is the lowest pulse-to-pulse fluctuation, to the best of our knowledge, obtained by the 100-mJ-class Ti:sapphire amplifiers.


The Relationship Between Glutamate Dynamics and Activity-Dependent Synaptic Plasticity.
The spatiotemporal dynamics of excitatory neurotransmission must be tightly regulated to achieve efficient synaptic communication. By limiting spillover, glutamate transporters are believed to prevent excessive activation of extrasynaptically located receptors that can impair synaptic plasticity. While glutamate transporter expression is reduced in numerous neurodegenerative diseases, the contributions of transporter dysfunction to disease pathophysiology remain ambiguous as the fundamental relationship between glutamate dynamics and plasticity, and the mechanisms linking these two phenomena, remain poorly understood. Here, we combined electrophysiology and real-time high-speed imaging of extracellular glutamate transients during LTP induction and characterized the sensitivity of the relationship between glutamate dynamics during theta burst stimulation (TBS) and the resulting magnitude of LTP consolidation, both in control conditions and following selective and nonselective glutamate transporter blockade. Glutamate clearance times were negatively correlated with LTP magnitude following nonselective glutamate transporter inhibition but not following selective blockade of a majority of GLT-1, the brain's most abundant glutamate transporter. Although glutamate transporter inhibition reduced the postsynaptic population response to TBS, calcium responses to TBS were greatly exaggerated. The source of excess calcium was dependent on NMDARs, L-type VGCCs, GluA2-lacking AMPARs, and internal calcium stores. Surprisingly, inhibition of L-type VGCCs, but not GluA2-lacking AMPARs or ryanodine receptors, was required to restore robust LTP. In all, these data provide a detailed understanding of the relationship between glutamate dynamics and plasticity and uncover important mechanisms by which poor glutamate uptake can negatively impact LTP consolidation.SIGNIFICANCE STATEMENT Specific patterns of neural activity can promote long-term changes in the strength of synaptic connections through a phenomenon known as synaptic plasticity. Synaptic plasticity is well accepted to represent the cellular mechanisms underlying learning and memory, and many forms of plasticity are initiated by the excitatory neurotransmitter glutamate. While essential for rapid cellular communication in the brain, excessive levels of extracellular glutamate can negatively impact brain function. In this study, we demonstrate that pharmacological manipulations that increase the availability of extracellular glutamate during neural activity can have profoundly negative consequences on synaptic plasticity. We identify mechanisms through which excess glutamate can negatively influence synaptic plasticity, and we discuss the relevance of these findings to neurodegenerative diseases and in the aging brain.


Risk factors for methicillin-resistant Staphylococcus aureus in diabetic foot infections.
The purpose of this study was to evaluate risk factors for methicillin-resistant Staphylococcus aureus (MRSA) in patients hospitalized for diabetic foot infections. We reviewed hospital admissions for foot infections in patients with diabetes which had nasal swabs, and anaerobic and aerobic tissue cultures at the time of admission. Data collected included patient characteristics and medical history to determine risk factors for developing an MRSA infection in the foot. The prevalence of MRSA in these infections was 29.8%. Risk factors for MRSA diabetic foot infections were history of MRSA foot infection, MRSA nasal colonization, and multidrug-resistant organisms (p<0.05). Positive predictive value (PPV) and negative predictive value (NPV) of nasal colonization with MRSA to identify MRSA diabetic foot infections were 66.7% and 80.0% (sensitivity 41%, specificity 90%). Admission from a nursing home was not a significant risk factor. Positive nasal swabs are not predictive of the infecting agent; however, a negative nasal swab rules out MRSA as the infecting agent in foot wounds with 90% accuracy.


SPATKIN: a simulator for rule-based modeling of biomolecular site dynamics on surfaces.
Rule-based modeling is a powerful approach for studying biomolecular site dynamics. Here, we present SPATKIN, a general-purpose simulator for rule-based modeling in two spatial dimensions. The simulation algorithm is a lattice-based method that tracks Brownian motion of individual molecules and the stochastic firing of rule-defined reaction events. Because rules are used as event generators, the algorithm is network-free, meaning that it does not require to generate the complete reaction network implied by rules prior to simulation. In a simulation, each molecule (or complex of molecules) is taken to occupy a single lattice site that cannot be shared with another molecule (or complex). SPATKIN is capable of simulating a wide array of membrane-associated processes, including adsorption, desorption and crowding. Models are specified using an extension of the BioNetGen language, which allows to account for spatial features of the simulated process. The C ++ source code for SPATKIN is distributed freely under the terms of the GNU GPLv3 license. The source code can be compiled for execution on popular platforms (Windows, Mac and Linux). An installer for 64-bit Windows and a macOS app are available. The source code and precompiled binaries are available at the SPATKIN Web site (http://pmbm.ippt.pan.pl/software/spatkin). firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Effect of Modified Cellulose Nanocrystals on the Structure of Calcium Silicate Hydrate Studied by Molecular Dynamics Simulation and Experiment.
The interfacial bonding of the four cellulose nanocrystals (CNCs) and calcium silicate hydrate (C-S-H) in vacuum and solution conditions was analyzed by molecular dynamics simulation. The binding energies were calculated, and the sources of interface strength were analyzed by the formation and lifetime of hydrogen bonds. The adsorption between CNC/C-S-H was characterized by the movement of interfacial atoms and CNC's adsorption conformation. The types of the functional group determine the bonding of the CNC/C-S-H, and the interface adsorption in two simulation conditions both followed: CNC-C (carboxyl) > CNC-O (hydroxyl) > CNC-N (amino) > CNC-S (sulfonic). The bonding of the interface affects the load transferred between the matrix and CNC, which can be reflected in the overall mechanical properties of the mortar. The mechanical strength of the mortar is in line with the simulation results. CNC-C has the strongest reinforcement effect, while CNC-S has the weakness effect. In the solution simulation, there is almost no chemical adsorption between C-S-H and CNC-S; instead, CNC-S decreased the bonding between the matrix and reduced the strength of the sample. Scanning electron microscopy found that CNC was interspersed in the matrix, riveting the matrix and enhanced the stability of the mortar structure. The influence of CNC on the mortar structure was analyzed by the calcium to silicon ratio (C/S) and it was showed that CNC-C, CNC-O, and CNC-N have an enhancement effect, while CNC-S decreased the coherence of the cement matrix. Durability and nuclear magnetic resonance tests further verified the effect of the four CNCs on the structure of mortar, and results indicated that CNC-C, CNC-O, and CNC-N can control the growth of hydration crystals, fill the cracks, and reduced porosity of samples, while CNC-S reduces the compactness of hydration products and ultimately decreased the mechanical and durability properties of the mortar.


Physical activity and survival after breast cancer diagnosis: meta-analysis of published studies.
Published data have shown that physical activity (PA) has a positive role on the primary prevention of breast cancer risk. However, the role of PA on breast cancer outcome has been controversial with inconsistent data. The lack of a meta-analysis that addresses that issue prompted the current report. A comprehensive literature search identified eight studies, of which two studies were excluded. The remaining six studies (12,108 patients with breast cancer) were included in this meta-analysis. Pre-diagnosis PA reduced all causes mortality by 18% but had no effect on breast cancer deaths. Post-diagnosis PA reduced breast cancer deaths by 34% (HR=0.66, 95% CI, 0.57-0.77, P<0.00001), all causes mortality by 41% (HR=0.59, 95% CI, 0.53-0.65, P<0.00001), and disease recurrence by 24% (HR=0.76, 95% CI, 0.66-0.87, P=0.00001). Breast cancer mortality was reduced by pre-diagnosis PA in women with body mass index (BMI)<25 kg/m2, while post-diagnosis PA reduced that risk among those with BMI≥25 kg/m2. On the other hand, post-diagnosis PA reduced all causes mortality regardless of the BMI. The analysis showed that post-diagnosis PA reduced breast cancer deaths (HR=0.50, 95% CI, 0.34-0.74, P=0.0005), and all causes mortality (HR=0.36, 95% CI, 0.12-1.03, P=0.06) among patients with estrogen receptor (ER)-positive tumor, while women with ER-negative disease showed no gain. The current meta-analysis provides evidence for an inverse relationship between PA and mortality in patients with breast cancer and supports the notion that appropriate PA should be embraced by breast cancer survivors.


A Survey of Genetic Variation and Genome Evolution within the Invasive Fallopia Complex.
The knotweed taxa Fallopia japonica, F. sachalinensis and their interspecific hybrid F. × bohemica are some of the most aggressive invaders in Europe and North America and they are serious threats to native biodiversity. At the same time, they constitute a unique model system for the creation of hybrids and studies of the initiation of evolutionary processes. In the presented study, we focused on (i) examining genetic diversity in selected populations of three Fallopia taxa in the invaded (Poland) and native ranges (Japan), (ii) establishing genome size and ploidy levels and (iii) identifying ribosomal DNA (rDNA)-bearing chromosomes in all of the taxa from the invaded range. We found that the genetic diversity within particular taxa was generally low regardless of their geographical origin. A higher level of clonality was observed for the Polish populations compared to the Japanese populations. Our study suggests that the co-occurrence of F. sachalinensis together with the other two taxa in the same stand may be the source of the higher genetic variation within the F. × bohemica hybrid. Some shift towards the contribution of F. japonica alleles was also observed for selected F. × bohemica individuals, which indicates the possibility of producing more advanced generations of F. × bohemica hybrids. All of the F. sachalinensis individuals were hexaploid (2n = 6x = 66; 2C = 6.01 pg), while those of F. japonica were mostly octoploid (2n = 8x = 88; 2C = 8.87 pg) and all of the F. × bohemica plants except one were hexaploid (2n = 6x = 66; 2C = 6.46 pg). Within the chromosome complement of F. japonica, F. sachalinensis and F. × bohemica, the physical mapping of the rDNA loci provided markers for 16, 13 and 10 chromosomes, respectively. In F. × bohemica, a loss of some of rDNA loci was observed, which indicates the occurrence of genome changes in the hybrid.


Enabling big geoscience data analytics with a cloud-based, MapReduce-enabled and service-oriented workflow framework.
Geoscience observations and model simulations are generating vast amounts of multi-dimensional data. Effectively analyzing these data are essential for geoscience studies. However, the tasks are challenging for geoscientists because processing the massive amount of data is both computing and data intensive in that data analytics requires complex procedures and multiple tools. To tackle these challenges, a scientific workflow framework is proposed for big geoscience data analytics. In this framework techniques are proposed by leveraging cloud computing, MapReduce, and Service Oriented Architecture (SOA). Specifically, HBase is adopted for storing and managing big geoscience data across distributed computers. MapReduce-based algorithm framework is developed to support parallel processing of geoscience data. And service-oriented workflow architecture is built for supporting on-demand complex data analytics in the cloud environment. A proof-of-concept prototype tests the performance of the framework. Results show that this innovative framework significantly improves the efficiency of big geoscience data analytics by reducing the data processing time as well as simplifying data analytical procedures for geoscientists.


Preliminary Evidence of Pregabalin Misuse among Prescription and/or Illicit Opioid (Mis)users.
Pregabalin is approved for the management of neuropathic pain, partial-onset seizures, and fibromyalgia. Although it is considered to have low potential for abuse, reports of misuse of pregabalin are emerging. The present study contributes to this literature by presenting preliminary evidence of pregabalin misuse. Mixed method interviews were conducted with prescription and/or illicit opioid (mis)users who reported a history of pregabalin misuse (N = 5). During semi-structured interviews, respondents provided descriptions of this practice, including motivation, route of administration, source, and drugs used/misused in combination with pregabalin. Motivations for pregabalin misuse included the self-treatment of physical pain (N = 1) and to achieve a desired psychoactive effect and/or combat opioid withdrawal symptoms (N = 4). Respondents described the misuse of pregabalin to potentiate the effects of heroin and cocaine, to feel "tipsy," and to experiment. We believe this report represents the first detailed contextual data about the misuse of pregabalin in the U.S. These misuse practices may represent an early indication of a growing problem. The recent permissibility of lower price generic versions has the potential to increase availability, decrease prices, and exacerbate pregabalin misuse.


A high number of oocytes obtained after ovarian hyperstimulation for in vitro fertilization or intracytoplasmic sperm injection is not associated with decreased pregnancy outcome.
To investigate the possible negative effects of a strong ovarian response on oocyte quality. Retrospective study. Tertiary academic center. A total of 1,894 women (IVF, n = 1,544; ICSI, n = 350) who underwent their first ovarian stimulation cycle during the period 1995-2002. Standardized controlled ovarian stimulation with urinary FSH or recombinant FSH after pituitary down-regulation, followed by IVF/intracytoplasmic sperm injection (ICSI) and ET. Fertilization rate, fraction of high-quality embryos, and implantation rate. Using multivariate logistic regression, we analyzed the effect, expressed as an odds ratio (OR), of the number of oocytes obtained (i.e., ovarian response) on the outcome measures. No effect of the response on the ongoing implantation rate or fraction of high-quality embryos was observed. Both in IVF (OR = 0.81, 95% confidence interval [CI] 0.75-0.87) and in ICSI (OR = 0.88, 95% CI 0.76-1.00), a negative effect of increasing ovarian response was seen on the fertilization rate per oocyte obtained. However, no negative effect was observed on the fertilization rate per oocyte injected in ICSI (OR = 1.00, 95% CI 0.87-1.14). The fraction of immature oocytes rises from 3.9%, in women with < or = 3 oocytes, to 26% in women with > 20 oocytes. Oocytes from high responders contain a greater fraction of immature oocytes, but pregnancy outcome is not impaired.


C-H···N hydrogen-bonding interaction in 7-azaindole:CHX3 (X=F, Cl) complexes.
The C-H···Y (Y=hydrogen-bond acceptor) interactions are somewhat unconventional in the context of hydrogen-bonding interactions. Typical C-H stretching frequency shifts in the hydrogen-bond donor C-H group are not only small, that is, of the order of a few tens of cm(-1) , but also bidirectional, that is, they can be red or blue shifted depending on the hydrogen-bond acceptor. In this work we examine the C-H···N interaction in complexes of 7-azaindole with CHCl3 and CHF3 that are prepared in the gas phase through supersonic jet expansion using the fluorescence depletion by infra-red (FDIR) method. Although the hydrogen-bond acceptor, 7-azaindole, has multiple sites of interaction, it is found that the C-H···N hydrogen-bonding interaction prevails over the others. The electronic excitation spectra suggest that both complexes are more stabilized in the S1 state than in the S0 state. The C-H stretching frequency is found to be red shifted by 82 cm(-1) in the CHCl3 complex, which is the largest redshift reported so far in gas-phase investigations of 1:1 haloform complexes with various substrates. In the CHF3 complex the observed C-H frequency is blue shifted by 4 cm(-1). This is at variance with the frequency shifts that are predicted using several computational methods; these predict at best a redshift of 8.5 cm(-1). This discrepancy is analogous to that reported for the pyridine-CHF3 complex [W. A. Herrebout, S. M. Melikova, S. N. Delanoye, K. S. Rutkowski, D. N. Shchepkin, B. J. van der Veken, J. Phys. Chem. A- 2005, 109, 3038], in which the blueshift is termed a pseudo blueshift and is shown to be due to the shifting of levels caused by Fermi resonance between the overtones of the C-H bending and stretching modes. The dissociation energies, (D0), of the CHCl3 and CHF3 complexes are computed (MP2/aug-cc-pVDZ level) as 6.46 and 5.06 kcal mol(-1), respectively.


Assessment of a Community-Based Exercise Program for Older Adults in a Mixed Rural/Urban Catchment Area: Silver Sneakers in Central Pennsylvania.
The purpose of our study was to understand the capacity of Silver Sneakers, a federally funded and community-based exercise program, to serve older adults (aged ≥65 years) in our mixed rural/urban catchment area of central Pennsylvania. We identified 139 registered Silver Sneakers program locations; of these, 18 were closed because of the COVID-19 pandemic. We used questionnaires to interview Silver Sneakers program staff by telephone (n = 80 of 121, response rate of 66%). Most programs were offered by private gyms (52%). Fewer programs were in rural counties than in urban counties. Most facilities reported that membership was equally mixed by gender, and member retention strategies included program perks and promotion of Silver Sneakers as a Medicare benefit. Most (89%) programs were able to continue classes during the pandemic, in part by adapting to video platforms. Overall, Silver Sneakers programs offer a sustainable option to facilitate access to exercise programs and reduce barriers to physical activity among older adults in our catchment area.


Comparative study of the different factors influencing resistance of tubes to gas flow.
With the help of a pneumotachograph and a pressure transducer the influences of tube diameter, tube length, tube shape, connectors of different shape and kinking are quantified. The influence of different gases on resistance is calculated. With the help of the shown data one can predict the influence of changes of the different factors. Rules for optimalisation are given and their clinical significance is discussed. Most significant factors are diameter and length of the tube, kinking over 50% and kinematic viscosity and density of the used gas mixture.


Phenotypic evaluation of natural and industrial Saccharomyces yeasts for different traits desirable in industrial bioethanol production.
Saccharomyces cerevisiae is the organism of choice for many food and beverage fermentations because it thrives in high-sugar and high-ethanol conditions. However, the conditions encountered in bioethanol fermentation pose specific challenges, including extremely high sugar and ethanol concentrations, high temperature, and the presence of specific toxic compounds. It is generally considered that exploring the natural biodiversity of Saccharomyces strains may be an interesting route to find superior bioethanol strains and may also improve our understanding of the challenges faced by yeast cells during bioethanol fermentation. In this study, we phenotypically evaluated a large collection of diverse Saccharomyces strains on six selective traits relevant for bioethanol production with increasing stress intensity. Our results demonstrate a remarkably large phenotypic diversity among different Saccharomyces species and among S. cerevisiae strains from different origins. Currently applied bioethanol strains showed a high tolerance to many of these relevant traits, but several other natural and industrial S. cerevisiae strains outcompeted the bioethanol strains for specific traits. These multitolerant strains performed well in fermentation experiments mimicking industrial bioethanol production. Together, our results illustrate the potential of phenotyping the natural biodiversity of yeasts to find superior industrial strains that may be used in bioethanol production or can be used as a basis for further strain improvement through genetic engineering, experimental evolution, or breeding. Additionally, our study provides a basis for new insights into the relationships between tolerance to different stressors.


Talin controls the exit of the integrin alpha 5 beta 1 from an early compartment of the secretory pathway.
Talin is a major cytosolic protein that links the intracellular domains of beta1 and beta3 integrins to the cytoskeleton. It is required for focal adhesion assembly. However, its downregulation not only slows down cell spreading and organization of focal adhesions but also impairs the maturation of some beta1 integrins, including the fibronectin receptor alpha5beta1. To investigate this, we characterized the beta1 integrin synthesized in cells expressing talin anti-sense RNA (AT22 cells). We identified a large intracellular pool of beta1 integrins that is abnormally accumulated in an earlier compartment of the secretory pathway. In this report, we show that in talin-deficient AT22 cells, the aberrant glycosylation of integrin receptors is accompanied by a delay in the export of the integrin alpha5beta1. In normal cells, talin was found associated with beta1 integrins in an enriched membrane fraction containing Golgi and endoplasmic reticulum. Finally, microinjection of anti-talin antibodies resulted in accumulation of the integrins within the cells. These data strongly suggest that talin plays a specific role in the export of newly synthesized integrins. We propose that talin binding to the integrin may disclose a diphenylalanine export signal, which is present in the membrane-proximal GFFKR motif conserved in all integrin alpha chains.


Identification and characterization of an enzyme involved in the elongation of n-6 and n-3 polyunsaturated fatty acids.
The enzymes that are involved in the elongation of fatty acids differ in terms of the substrates on which they act. To date, the enzymes specifically involved in the biosynthesis of polyunsaturated fatty acids have not yet been identified. In an attempt to identify a gene(s) encoding an enzyme(s) specific for the elongation of gamma-linolenic acid (GLA) (18:3n-6), a cDNA expression library was made from the fungus Mortierella alpina. The cDNA library constructed in a yeast expression vector was screened by measuring the expressed elongase activity [conversion of GLA to dihomo-GLA (20:3n-6)] from an individual yeast clone. In this report, we demonstrate the isolation of a cDNA (GLELO) whose encoded protein (GLELOp) was involved in the conversion of GLA to dihomo-GLA in an efficient manner (60% conversion). This cDNA contains a 957-nucleotide ORF that encodes a protein of 318 amino acids. Substrate specificity analysis revealed that this fungal enzyme acted also on stearidonic acid (18:4n-3). This report identifies and characterizes an elongase subunit that acts specifically on the two Delta6-desaturation products, 18:3n-6 and 18:4n-3. When this GLELO cDNA was coexpressed with M. alpina Delta5-desaturase cDNA in yeast, it resulted in the conversion of GLA to arachidonic acid (20:4n-6) as well as the conversion of stearidonic acid to eicosopentaenoic acid (20:5n-3). Thus, this GLELO gene may play an critical role in the bio-production of both n-6 and n-3 polyunsaturated fatty acids.


Triple Therapy with Budesonide/Glycopyrrolate/Formoterol Fumarate Improves Inspiratory Capacity in Patients with Asthma-Chronic Obstructive Pulmonary Disease Overlap.
Asthma-chronic obstructive pulmonary disease overlap (ACO), characterized by airway limitation, is an important condition with high incidence and mortality. Although some guidelines recommend triple therapy with inhaled corticosteroids/long-acting muscarinic antagonists/long-acting β2 agonists, this treatment approach is based on the extrapolation of data from studies of asthma or chronic obstructive pulmonary disease (COPD) alone. A 12-week, randomized, open-label cross-over pilot study was conducted in 19 patients with ACO to investigate the effect of triple therapy with glycopyrrolate (GLY) 50 µg/day on budesonide/formoterol fumarate (BUD/FORM) 640/18 µg/day. The study period included a 4-week wash-out, 4-week run-in, and 4-week treatment period. Respiratory function tests, fractional exhaled nitric oxide (FeNO), a COPD assessment test (CAT) and an asthma control questionnaire (ACQ) were carried out 0, 4, and 8 weeks after randomization. A total of 19 patients with stable ACO (19 males and no females) with a mean age of 70.7 ± 7.6 years (± standard deviation, SD; range 55-83 years) participated in this study. All patients were ex-smokers with a smoking history of 63.1 ± 41.1 pack-years (± SD). Mean values for inspiratory capacity (IC), an index of hyperinflation of the lung that causes exertional dyspnea and reduced exercise, were 1.93 L (± 0.47 L) after the run-in, 1.85 L (± 0.51 L) after the BUD/FORM dual therapy period and 2.11 L (± 0.58 L) after the BUD/GLY/FORM triple therapy period. IC values after the BUD/GLY/FORM triple therapy were significantly higher than those after the run-in (p < 0.02). FeNO values, ACQ, and CAT scores were not significantly different among the run-in, wash-out, and triple-therapy periods. The present pilot study showed that triple therapy with BUD/GLY/FORM results in an improvement in lung function parameters including IC, indicating the potential value of triple therapy as standard treatment for ACO.


Papillary cystadenocarcinoma of the hard palate.
Papillary cystadenocarcinoma (PCC) is an uncommon malignant tumour of the salivary gland, sometimes involving the minor salivary gland. Previously this entity was classified as an atypical type of adenocarcinoma, malignant papillary cystadenoma, low-grade papillary adenocarcinoma or mucus producing adenopapillary carcinoma. PCC is a glandular tumour with an indolent biological behaviour characterised by cysts and papillary endophytic projections. We report two cases of PCC involving the minor salivary gland of the hard palate. Both the patients presented with a swelling in the palate with difficulty in chewing. MRI revealed an extensively destructive lesion involving hard palate, alveolar ridge and maxillary antrum. Clinical and radiological features suggested the malignant nature of the lesion. Histopathology of incisional biopsy revealed tumour proliferation in a multicystic pattern, with extensive papillary proliferation. Diverse and cellular cytomorphology, and cellular and nuclear pleomorphism with few mitotic figures were the prominent features. Both the lesions were confirmed as PCC.


Long-term time trends in human intake of POPs in the Czech Republic indicate a need for continuous monitoring.
Polychlorinated biphenyls (PCBs) and organochlorine pesticides (OCPs) from the group of persistent organic pollutants are detected in human tissues years or even decades after their ban. Exposure to PCBs and OCPs can pose risks to human health. In the present study, we calculated the daily intakes of PCBs and OCPs in the Czech population and investigated the long-term trends of human exposure to POPs. Data on POP concentrations from a 16-year period of breast-milk monitoring were used. A toxicokinetic model with consideration of compound-specific elimination half-lives was used to calculate the mothers' daily intake of PCBs and OCPs representing the intake of POPs by all exposure routes. The calculated intakes were compared with dietary intakes calculated by the Czech National Institute of Public Health. The comparison shows good agreement of both intake estimates with decreasing intake trends of POPs in the Czech population in the time period studied. However, several fluctuations with peaks of higher levels were observed in both datasets which are not typical for the period after the ban of use and production of POPs. The available evidence suggests that the increases in chemical concentrations might be caused by food contamination. The calculated intakes of compounds with longer elimination half-lives, such as higher-chlorinated PCBs, were higher in older mothers. This "memory effect" was already observed in other studies and indicates higher exposure in earlier life periods of the mother. Our results suggest that exposure to POPs is still relevant for the Czech population in the period after the ban of the use and production of POPs (post-ban period), especially via food ingestion, though the intake trends are decreasing. Possible food contamination by POPs in the post-ban period requires further assessment.


EUS-guided Biliary Drainage for Malignant Perihilar Biliary Strictures after Further Transpapillary Intervention Has Been Judged to Be Impossible or Ineffective.
Objective Patients with perihilar malignancy often develop recurrence of infectious cholangitis, which makes further transpapillary intervention extremely difficult. As endoscopic ultrasound (EUS)-guided biliary drainage (EUS-BD) of an intrahepatic bile duct is a possible option for additional intervention, the aim of this study was to estimate the feasibility of such intervention. Methods and Patients Patients who had undergone EUS-BD after further transpapillary intervention was deemed impossible or ineffective were investigated in this study. Those who had not received previous interventions via the papilla were excluded. Procedure-related adverse events, clinical efficacy, and time to recurrence of jaundice or infectious cholangitis transthyretin (TTR) were evaluated. Results Seven patients were eligible for the study between 2007 and 2016 (7 men; mean age, 77 years; 4 with perihilar cholangiocarcinoma and 3 with intrahepatic cholangiocarcinoma). No procedure-related adverse events were observed. EUS-BD was clinically effective and enabled hospital discharge in 4 patients (57%). The TTR in these 4 clinically effective patients was 43, 105, 118, and 147 days after the procedure (median, 112 days). Conclusion EUS-BD was found to be safe and often effective in patients in whom additional transpapillary intervention had become difficult, although its efficacy was limited to a short period.


Favorable effects of motivational interviewing and support in a patient with schizophrenia and alcohol abuse.
A 42-year-old man with schizophrenia was referred to our hospital after 2 weeks of worsening fatigue. His hemoglobin level was 2.8 g/dL owing to folic acid deficiency stemming from alcohol abuse and consumption of unbalanced meals. We induced behavioral changes in the patient by motivational interviewing. We had direct methodical conversations with medical staff involved with the patient as well as his family, and established new social support for him as well as public assistance. These have resulted in the patient maintaining a favorable lifestyle ever since.


Single-Cell Mass Cytometry of Acute Myeloid Leukemia and Leukemia Stem/Progenitor Cells.
Mass cytometry time-of-flight (CyTOF) empowers us to understand acute myeloid leukemia (AML) biology at the single-cell level. This technology, combined with advanced data-analysis methods, enables identification and characterization of the rare AML stem/progenitor cells that play key roles in drug resistance and AML relapse. Here we provide a protocol for AML sample preparation for CyTOF and keynotes emphasizing critical steps in and troubleshooting strategies for this procedure.


Complex diabetes screening guidelines for high-risk adolescent Aboriginal Australians: a barrier to implementation in primary health care.
The aim of this study is to ascertain whether a simplified screening algorithm incorporating glycated haemoglobin (HbA1c) tests increases type 2 diabetes (T2D) screening in 10- to 14-year-old Aboriginal Australians presenting to primary healthcare (PHC) services. The study involved a 6-month pilot of a locally developed evidence-based screening algorithm in a remote Western Australian Kimberley town. A retrospective audit of electronic health records for the pilot period (27 June-26 December 2016) and a 6-month period before the screening algorithm was introduced (1 October 2015-31 March 2016) was conducted. Interviews were held with 30 PHC staff at participating PHC services, an Aboriginal Community Controlled Health Service (ACCHS) and a hospital-based general practice service. During the pilot, significantly more patients received an initial T2D screening test at the ACCHS (28/130 (22%) v. 50/139 (36%), P = 0.011), but there was no change at the hospital (0.02% v. 0.02%, P = 0.615). Staff feedback suggested measures to improve screening; these include simple guidelines, targeted screening, patient and staff education, point-of-care HbA1c tests and a whole-of-clinic approach to implementation. Implementing a screening algorithm for young-onset diabetes in Aboriginal Australians is challenging, but practical measures can be taken to improve screening.


Evaluation of anti-inflammatory activity and molecular docking study of new aza-bicyclic isoxazoline acylhydrazone derivatives.
The aim of this study was to investigate the anti-inflammatory effects of two new isoxazoline-acylhydrazone derivatives: N'-(4-methoxybenzylidene)-6-(4-nitro-benzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-123) and N'-(4-chlorobenzylidene)-6-(4-chlorobenzoyl)-3a,5,6,6a-tetrahydro-4H-pyrrolo[3,2-d]isoxazole-3-carbohydrazide (R-99). An air pouch induced by carrageenan was used for screening the best dose of R-99 and R-123. Using this mouse model, leukocyte migration and cytokine levels (TNF-α and IL-1β) were determined. Paw edema induced by several phlogistic agents and vascular permeability induced by acetic acid were employed to investigate the mechanism of action of the isoxazoline-acylhydrazone derivatives. A docking study was performed with the human histamine H1 receptor to investigate potential antihistaminic activity. Treatment with the compounds reduced leukocyte migration in the air pouch at all doses tested. TNF-α and IL-1β levels were similarly reduced by the two compounds. Vasoactive amines were inhibited in models of paw edema induced by several agents and vascular permeability induced by acetic acid. The docking study suggests that R-99 and R-123 may be inhibitors of the histamine H1 receptor. In conclusion, the results indicate that R-99 and R-123 exhibit promising anti-inflammatory activity related to their ability to inhibit TNF-α, IL-1β, and vasoactive amine production, as well as reduce leukocyte migration and inhibit mast cell degranulation.


Simultaneous Metacarpophalangeal Dislocation and Carpometacarpal Fracture-Dislocation of the Ring Finger: A Case Report.
Fracture-dislocations of the carpometacarpal (CMC) joints are pretty uncommon injuries with an incidence of 1%. A 17-year-old male was referred due to multiple traumas following a car accident with Glasgow Coma Score of 9. Simultaneous metacarpophalangeal dislocation and CMC fracture-dislocation of the ring finger were present in the 4th finger (ring finger) of the right hand. Closed reduction and short arm splint in the intrinsic plus position was applied, and full range of motion was accomplished after 1 year postoperatively. High clinical suspicion with adequate plain radiographs are required to diagnose precisely CMC fracture-dislocation injuries. To the best of our knowledge, any case report similar to the nature of the present injury has yet to be reported to date, addressing CMC fracture-dislocation of the ring finger and concomitant volar MCP joint dislocation in the same finger. Therefore, we can make the argument that our case report is unique.


Why Wealthier People Think People Are Wealthier, and Why It Matters: From Social Sampling to Attitudes to Redistribution.
The present studies provide evidence that social-sampling processes lead wealthier people to oppose redistribution policies. In samples of American Internet users, wealthier participants reported higher levels of wealth in their social circles (Studies 1a and 1b). This was associated, in turn, with estimates of higher mean wealth in the wider U.S. population, greater perceived fairness of the economic status quo, and opposition to redistribution policies. Furthermore, results from a large-scale, nationally representative New Zealand survey revealed that low levels of neighborhood-level socioeconomic deprivation-an objective index of wealth within participants' social circles-mediated the relation between income and satisfaction with the economic status quo (Study 2). These findings held controlling for relevant variables, including political orientation and perceived self-interest. Social-structural inequalities appear to combine with social-sampling processes to shape the different political attitudes of wealthier and poorer people.


Sepsis induced cardiotoxicity by promoting cardiomyocyte cuproptosis.
Currently, sepsis induced cardiotoxicity is among the major causes of sepsis-related death. The specific molecular mechanisms of sepsis induced cardiotoxicity are currently unknown. Therefore, the purpose of this paper is to identify the key molecule mechanisms for sepsis induced cardiotoxicity. Original data of sepsis induced cardiotoxicity was derived from Gene Expression Omnibus (GEO; GSE63920; GSE44363; GSE159309) dataset. Functional enrichment analysis was used to analysis sepsis induced cardiotoxicity related signaling pathways. Our findings also have explored the relationship of cuproptosis and N6-Methyladenosine (m6A) in sepsis induced cardiotoxicity. Mice are randomly assigned to 3 groups: saline treatment control group, LPS group administered a single 5 mg/kg dose of LPS for 24 h, LPS + CD274 inhibitor group administered 10 mg/kg CD274 inhibitor for 24 h. Overall, expression of cuproptosis-related genes (CRGs) CD274, Ceruloplasmin (CP), Vascular endothelial growth factor A (VEGFA), Copper chaperone for cytochrome c oxidase 11 (COX11), chemokine C-C motif ligand 8 (CCL8), Mitogen-activated protein kinase kinase 1(MAP2K1), Amine oxidase 3 (AOC3) were significantly altered in sepsis induced cardiotoxicity. The results of spearman correlation analysis was significant relationship between differentially regulated genes (DEGs) of CRGs and the expression level of m6A methylation genes. GO and KEGG showed that these genes were enriched in response to interferon-beta, MHC class I peptide loading complex, proteasome core complex, chemokine receptor binding, TAP binding, chemokine activity, cytokine activity and many more. These findings suggest that cuproptosis is strongly associated with sepsis induced cardiotoxicity. In the present study, we found that cuproptosis were associated with sepsis induced cardiotoxicity. The CD274, CP, VEGFA, COX11, CCL8, MAP2K1, AOC3 genes are showing a significant difference expression in sepsis induced cardiotoxicity. Our studies have found significant correlations between CRGs and m6A methylation related genes in sepsis induced cardiotoxicity. These results provide insight into mechanism for sepsis induced cardiotoxicity.


Audiological investigation of palatal myoclonus.
Palatal myoclonus, the rapid rhythmic contraction of palatal muscles, is a rare neurological disorder with many etiologies. Although most disease processes associated with this disorder affect the cerebellum, the auditory symptoms are often the first clue to diagnosis. Existing literature was reviewed in terms of auditory symptoms, pathophysiology, audiologic diagnostic procedures and rehabilitative strategies. In addition, a case study of a 34-yr-old woman who has had this highly peculiar degenerative disorder for over 20 yrs was described. Implications for appropriate rehabilitation strategies were addressed and the importance of comprehensive management was stressed.


Laser-Based Manufacturing of Ceramics: A Review.
Ceramics are widely used in microelectronics, semiconductor manufacturing, medical devices, aerospace, and aviation, cutting tools, precision optics, MEMS and NEMS devices, insulating components, and ceramic molds. But the fabrication and machining of the ceramic-based materials by conventional processes are always difficult due to their higher hardness and mechanical properties. Therefore, advanced manufacturing techniques are being preferred for these advanced materials, and out of that, laser-based processes are widely used. The benefits of laser fabrication and machining of ceramics include high precision, reduced thermal damage, non-contact processing, and the ability to work with complex geometries. Laser technology continues to advance, enabling even more intricate and diverse applications for ceramics in a wide range of industries. This paper explains various laser based ceramic processing techniques, such as selective laser sintering and melting, and laser machining techniques, such as laser drilling, etc. Identifying and optimizing the process parameters that influence the output quality of laser processed parts is the key technique to improving the quality, which is also focused on in this paper. It aims to facilitate the researchers by providing knowledge on laser-based manufacturing of ceramics and their composites to establish the field further.


The roll-bar hand.
This report describes a new hand injury seen in passengers in dune buggies having rollover accidents. Since these vehicles are usually driven off the road and far from treatment centers the treatment of these injuries is often delayed. As the rollover takes place, the reflex action--usually of the passenger--is to grasp the roll bar. A crush-avulsion injury occurs at the level of the metacarpals, with the thumb frequently spared. Wound contamination, delay in treatment, and the frequency of other serious injuries add to the seriousness of this injury. Redesign of the roll bar, provision of better passenger protection, and an internal grasp support are suggested to reduce its incidence.


Effect of monensin on the assembly of Uukuniemi virus in the Golgi complex.
The effect of the carboxylic ionophore monensin on the maturation of Uukuniemi virus, a bunyavirus, and the transport of its two membrane glycoproteins, G1 and G2, were studied in chicken embryo fibroblasts and baby hamster kidney cells. Virus maturation, which occurs in the Golgi complex (E. Kuismanen, K. Hedman, J. Saraste, and R. F. Pettersson, Mol. Cell. Biol. 2:1444-1458, 1982; E. Kuismanen, B. Bång, M. Hurme, and R. F. Pettersson, J. Virol. 51:137-146, 1984), was effectively inhibited by the drug (1 or 10 microM) as studied by electron microscopy and by assaying the release of infectious or radiolabeled virus. Immunoelectron microscopy showed that association of viral nucleocapsids with the cytoplasmic surface of glycoprotein-containing Golgi membranes, a prerequisite for virus budding, was unaffected by monensin. In the presence of the drug, the virus glycoproteins assembled into long, tubular structures extending into the lumen of Golgi-derived vacuoles, suggesting that monensin inhibited a terminal step in the assembly of the virus. Intracellular transport and expression of the virus membrane glycoproteins G1 and G2 at the cell surface were not inhibited by monensin as studied by immunocytochemical and radiolabeling techniques. Pulse-chase experiments in the presence of monensin showed that intracellular G1 acquired only partially endo-H-resistant glycans. The sialylation of G1 appearing on the cell surface in the presence of the drug was decreased, whereas sialylation of G2 apparently was inhibited to a lesser extent, as shown by external labeling of the cells with the periodate-boro[3H]hydride method. Thus, monensin exerted a differential effect on the terminal glycosylation of G1 and G2. Unlike several membrane and secretory glycoproteins, both G1 and G2 could enter a functional transport pathway in the presence of monensin and become expressed at the cell surface.


Force transmission between synergistic skeletal muscles through connective tissue linkages.
The classic view of skeletal muscle is that force is generated within its muscle fibers and then directly transmitted in-series, usually via tendon, onto the skeleton. In contrast, recent results suggest that muscles are mechanically connected to surrounding structures and cannot be considered as independent actuators. This article will review experiments on mechanical interactions between muscles mediated by such epimuscular myofascial force transmission in physiological and pathological muscle conditions. In a reduced preparation, involving supraphysiological muscle conditions, it is shown that connective tissues surrounding muscles are capable of transmitting substantial force. In more physiologically relevant conditions of intact muscles, however, it appears that the role of this myofascial pathway is small. In addition, it is hypothesized that connective tissues can serve as a safety net for traumatic events in muscle or tendon. Future studies are needed to investigate the importance of intermuscular force transmission during movement in health and disease.


Discrepancies between net particulate carbon production and (13) C-labelled bicarbonate uptake by Alexandrium catenella (Dinophyceae): grazing controls the balance between autotrophic and non autotrophic carbon acquisition(1).
Inorganic carbon uptake by Alexandrium catenella estimated from incorporation of (13) C labelled bicarbonate (an estimate of carbon gain by autotrophy) was compared to increases in particulate carbon (PC) that integrate all processes leading to carbon gain by cells (autotrophy, heterotrophy, mixotrophy). During blooms of A. catenella in the field, the (13) C tracer technique could account for only 47% (range 29%-59%) of the increase in PC in conventional 24 h incubations. From dilution experiments, the ratio of PC increases to bicarbonate uptake was related significantly and positively to the grazing rate, indicating that dissolved organic carbon contributes to growth as a direct function of grazing activity. In addition, as grazing rate increases, the contribution of dissolved inorganic carbon uptake to carbon-based growth decreases in a linear way (from 56% to 33% of total C acquisition) and the contribution of non autotrophic processes increases (from 54% to 67%). Thus, grazing appears to closely control the balance between autotrophic and non autotrophic processes leading to carbon acquisition by natural populations of A. catenella.


Bimaxillary reconstruction with a single free fibular osteoseptocutaneous flap.
Flap combinations including free fibula have been commonly used to reconstruct composite maxillomandibular defects. On the other hand, a single free osteoseptocutaneous may be rarely used to reconstruct the bimaxilla. In this article, we report a bimaxillary reconstruction in a 63-year-old man with a single fibular osteoseptocutaneous free flap.


Loperamide misuse to avoid opioid withdrawal and to achieve a euphoric effect: high doses and high risk.
Loperamide is a readily accessible nonprescription medication that is increasingly being used surreptitiously as an opioid substitute to alleviate the symptoms of acute opioid withdrawal. The objective of this study was to determine the clinical characteristics of patients with loperamide misuse and toxicity. The ToxIC registry, a nationwide, prospectively collected cohort of patients evaluated by medical toxicologists was searched from November 2011-December 2016 for patients with loperamide exposure. Each record was reviewed to determine the circumstances, dose, clinical presentations, treatment, and outcomes associated with loperamide use. Twenty-six cases were identified, and both the absolute number and relative proportion of overall cases in the ToxIC registry increased annually. The median age was 27 and 54% were male. Of cases with known intent (n = 18), 12(67%) were misuse/abuse, 3(17%) were self-harm/suicide, and 3(17%) were pediatric exploratory ingestions. Circumstances for misuse included taking higher doses than labeled (n =7), avoiding withdrawal (n = 6), and gaining a pleasurable sensation (n =4). The dose was reported in nine cases and ranged from 4 mg to 400 mg. In patients seeking to avoid withdrawal doses were 160-400 mg/day; the most common reported dose was 200 mg. Reported ECG abnormalities included 10 cases of prolonged QTc (>500 ms), which consisted of misuse/abuse (n =6) and self-harm (n =1) exposures; six prolonged QRS (>120 ms); two first degree AV block; seven ventricular dysrhythmias, five of which were single-agent exposures. All but one ECG demonstrated prolonged QTc with a range of 566-749 ms. All patients with dysrhythmias in which dose were reported ingested ≥200 mg. The majority of patients had loperamide toxicity due to misuse/abuse, in-line with national trends. In patients avoiding withdrawal, doses >100 mg were observed. When taken in large doses (>200 mg), loperamide may cause significant cardiovascular effects, including QTc-prolongation and ventricular dysrhythmias.


[Nutritional aspects associated with chronic Trypanosoma cruzi (Chagas 1909) infection among older adults: Bambuí Project].
The aim of the study was to verify nutritional aspects associated with chronic Trypanosoma cruzi infection among baseline participants from the Bambuí cohort study on aging. The analysis included 84.9% (1,479) of residents of Bambuí, Minas Gerais State, Brazil, who were 60 years or older in 1997. T. cruzi infection was investigated by three serological tests, and nutritional status was assessed by anthropometric and biochemical variables. Associations were evaluated by prevalence ratios and confidence intervals (95%CI) using Poisson regression. T. cruzi infection was present in 38.1% of patients. All anthropometric variables were significantly associated with infection, showing lower values among patients with positive serology. No biochemical variables were associated with infection. The results showed the coexistence of chronic Chagas disease and poor nutritional status in the study population, reinforcing the importance of nutritional evaluation among elderly people presenting chronic T. cruzi infection.


Identifying consistent allele frequency differences in studies of stratified populations.
With increasing application of pooled-sequencing approaches to population genomics robust methods are needed to accurately quantify allele frequency differences between populations. Identifying consistent differences across stratified populations can allow us to detect genomic regions under selection and that differ between populations with different histories or attributes. Current popular statistical tests are easily implemented in widely available software tools which make them simple for researchers to apply. However, there are potential problems with the way such tests are used, which means that underlying assumptions about the data are frequently violated.These problems are highlighted by simulation of simple but realistic population genetic models of neutral evolution and the performance of different tests are assessed. We present alternative tests (including Generalised Linear Models [GLMs] with quasibinomial error structure) with attractive properties for the analysis of allele frequency differences and re-analyse a published dataset.The simulations show that common statistical tests for consistent allele frequency differences perform poorly, with high false positive rates. Applying tests that do not confound heterogeneity and main effects significantly improves inference. Variation in sequencing coverage likely produces many false positives and re-scaling allele frequencies to counts out of a common value or an effective sample size reduces this effect.Many researchers are interested in identifying allele frequencies that vary consistently across replicates to identify loci underlying phenotypic responses to selection or natural variation in phenotypes. Popular methods that have been suggested for this task perform poorly in simulations. Overall, quasibinomial GLMs perform better and also have the attractive feature of allowing correction for multiple testing by standard procedures and are easily extended to other designs.


Financial Impact of Postoperative Complication Following Hepato-Pancreatico-Biliary Surgery for Cancer.
Despite increasing efforts for cost containment, little is known regarding the financial implications of postoperative complication under current volume-driven payment paradigms. This study sought the test the associations between hospital finances and postoperative complications among hepato-pancreatico-bilary cancer patients. Patients undergoing surgery for the management of a hepatobiliary or pancreatic cancer between January 1, 2009 and December 31, 2013 were identified using institutional claims and cost-accounting data. Multivariable linear regression analyses were used to calculate risk-adjusted fixed and variable costs, payments, and net margins. A total of 1483 met inclusion criteria. Fixed ($9290 [interquartile range (IQR) $7129-$11,598] vs. $14,784 [IQR $10,523-$22,799], p < 0.001) and variable costs ($12,342 [IQR $9886-$14,762] vs. $19,330 [IQR $13,967-$29,435], p < 0.001) were higher among patients who developed a postoperative complication following a hepatectomy. A higher contribution margin ($12,421 [IQR $8440-$16,445] vs. $20,016 [IQR $14,212-$39,179], p < 0.001), as well as a twofold higher net profit was noted among patients who developed postoperative complication ($2788 [IQR $660-$5815] vs. $5515 [IQR $1068-$10,315], p < 0.001). Total hospital costs ($26,840 [IQR $21,318-$35,358] vs. $46,628 [IQR $31,974-$69,326], p < 0.001) as well as payments ($32,761 [IQR $26,394-$41,883] vs. $53,612 [IQR $38,548-$78,116], p < 0.001) were more than 1.5 times higher among patients who developed a postoperative complication following pancreatic resection. Contribution margins ($18,356 [IQR $14,024-$24,390] vs. $29,153 [IQR $20,256-$41,785], p < 0.001), as well as net profits ($5907 [IQR $2179-$9412] vs. $8114 [IQR $2518-$14,249], p < 0.001) were higher among patients who developed postoperative complication following pancreatic surgery. A positive association was observed between net profits and postoperative complications. Future policies should target complications as a means to achieving a higher value for care.