[Experts consensus on the management of the right heart function in critically ill patients].
To establish the experts consensus on the right heart function management in critically ill patients. The panel of consensus was composed of 30 experts in critical care medicine who are all members of Critical Hemodynamic Therapy Collaboration Group (CHTC Group). Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 52 experts to reassess all the statements. (1) Right heart function is prone to be affected in critically illness, which will result in a auto-exaggerated vicious cycle. (2) Right heart function management is a key step of the hemodynamic therapy in critically ill patients. (3) Fluid resuscitation means the process of fluid therapy through rapid adjustment of intravascular volume aiming to improve tissue perfusion. Reversed fluid resuscitation means reducing volume. (4) The right ventricle afterload should be taken into consideration when using stroke volume variation (SVV) or pulse pressure variation (PPV) to assess fluid responsiveness.(5)Volume overload alone could lead to septal displacement and damage the diastolic function of the left ventricle. (6) The Starling curve of the right ventricle is not the same as the one applied to the left ventricle,the judgement of the different states for the right ventricle is the key of volume management. (7) The alteration of right heart function has its own characteristics, volume assessment and adjustment is an important part of the treatment of right ventricular dysfunction (8) Right ventricular enlargement is the prerequisite for increased cardiac output during reversed fluid resuscitation; Nonetheless, right heart enlargement does not mandate reversed fluid resuscitation.(9)Increased pulmonary vascular resistance induced by a variety of factors could affect right heart function by obstructing the blood flow. (10) When pulmonary hypertension was detected in clinical scenario, the differentiation of critical care-related pulmonary hypertension should be a priority. (11) Attention should be paid to the change of right heart function before and after implementation of mechanical ventilation and adjustment of ventilator parameter. (12) The pulmonary arterial pressure should be monitored timingly when dealing with critical care-related pulmonary hypertension accompanied with circulatory failure.(13) The elevation of pulmonary aterial pressure should be taken into account in critical patients with acute right heart dysfunction. (14) Prone position ventilation is an important measure to reduce pulmonary vascular resistance when treating acute respiratory distress syndrome patients accompanied with acute cor pulmonale. (15) Attention should be paid to right ventricle-pulmonary artery coupling during the management of right heart function. (16) Right ventricular diastolic function is more prone to be affected in critically ill patients, the application of critical ultrasound is more conducive to quantitative assessment of right ventricular diastolic function. (17) As one of the parameters to assess the filling pressure of right heart, central venous pressure can be used to assess right heart diastolic function. (18). The early and prominent manifestation of non-focal cardiac tamponade is right ventricular diastolic involvement, the elevated right atrial pressure should be noticed. (19) The effect of increased intrathoracic pressure on right heart diastolic function should be valued. (20) Ttricuspid annular plane systolic excursion (TAPSE) is an important parameter that reflects right ventricular systolic function, and it is recommended as a general indicator of critically ill patient. (21) Circulation management with right heart protection as the core strategy is the key point of the treatment of acute respiratory distress syndrome. (22) Right heart function involvement after cardiac surgery is very common and should be highly valued. (23) Right ventricular dysfunction should not be considered as a routine excuse for maintaining higher central venous pressure. (24) When left ventricular dilation, attention should be paid to the effect of left ventricle on right ventricular diastolic function. (25) The impact of left ventricular function should be excluded when the contractility of the right ventricle is decreased. (26) When the right heart load increases acutely, the shunt between the left and right heart should be monitored. (27) Attention should be paid to the increase of central venous pressure caused by right ventricular dysfunction and its influence on microcirculation blood flow. (28) When the vasoactive drugs was used to reduce the pressure of pulmonary circulation, different effects on pulmonary and systemic circulation should be evaluated. (29) Right atrial pressure is an important factor affecting venous return. Attention should be paid to the influence of the pressure composition of the right atrium on the venous return. (30) Attention should be paid to the role of the right ventricle in the acute pulmonary edema. (31) Monitoring the difference between the mean systemic filling pressure and the right atrial pressure is helpful to determine whether the infusion increases the venous return. (32) Venous return resistance is often considered to be a insignificant factor that affects venous return, but attention should be paid to the effect of the specific pathophysiological status, such as intrathoracic hypertension, intra-abdominal hypertension and so on. Consensus can promote right heart function management in critically ill patients, optimize hemodynamic therapy, and even affect prognosis.


CDF-XL: computing cumulative distribution functions of reaction time data in Excel.
In experimental psychology, central tendencies of reaction time (RT) distributions are used to compare different experimental conditions. This emphasis on the central tendency ignores additional information that may be derived from the RT distribution itself. One method for analysing RT distributions is to construct cumulative distribution frequency plots (CDFs; Ratcliff, Psychological Bulletin 86:446-461, 1979). However, this method is difficult to implement in widely available software, severely restricting its use. In this report, we present an Excel-based program, CDF-XL, for constructing and analysing CDFs, with the aim of making such techniques more readily accessible to researchers, including students (CDF-XL can be downloaded free of charge from the Psychonomic Society's online archive). CDF-XL functions as an Excel workbook and starts from the raw experimental data, organised into three columns (Subject, Condition, and RT) on an Input Data worksheet (a point-and-click utility is provided for achieving this format from a broader data set). No further preprocessing or sorting of the data is required. With one click of a button, CDF-XL will generate two forms of cumulative analysis: (1) "standard" CDFs, based on percentiles of participant RT distributions (by condition), and (2) a related analysis employing the participant means of rank-ordered RT bins. Both analyses involve partitioning the data in similar ways, but the first uses a "median"-type measure at the participant level, while the latter uses the mean. The results are presented in three formats: (i) by participants, suitable for entry into further statistical analysis; (ii) grand means by condition; and (iii) completed CDF plots in Excel charts.


Should pancreatectomy with islet cell autotransplantation in patients with chronic alcoholic pancreatitis be abandoned?
Pancreatectomy or drainage has been advocated for pain due to chronic pancreatitis. Islet cell autotransplantation (IAT) may improve quality of life (QOL); optimal patient selection has not been established. Outcomes of 100 patients who underwent pancreatectomy with islet isolation between 2005 and 2012 were assessed by etiology (alcoholic pancreatitis [AP] 30%, and nonalcoholic pancreatitis [NAP] 70%). Insulin requirement, Short Form-36, and McGill Pain Questionnaires were assessed. Data were analyzed using SASv9.2. Of the 100 patients, isolation was unsuccessful in 9 patients due to fibrosis. Alcoholic pancreatitis was associated with 7 of 9 failed isolations (23% vs 3%, p < 0.01), and all of these patients are now diabetic. Ninety-one patients (age 44 years, follow-up 19 months, 23% AP) underwent resection with IAT. Total islet yield (islet cell equivalents [IEQ]) and IEQ/kg body weight were less for patients with AP (81,000 vs 150,000, p < 0.01; 1,260 vs 2,190, respectively, p = 0.01) overall and more specifically, for total pancreatectomy (92,000 vs 188,000, respectively, p = 0.02). Twenty-eight (34%) of all patients who had resections and 15% of those undergoing total pancreatectomy are insulin free. Multivariate analysis identified AP as an independent predictor of insulin units/day (p = 0.01). Complete pre- and postoperative QOL and pain surveys were available on 69 patients. Patients with AP had less QOL improvement (1 of 8 vs 5 of 8 domains, p < 0.01) and "present pain" improvement at 2 years from preoperative levels in those with NAP; no improvement in QOL was seen in those with AP (NAP 2.7 to 1.2, p < 0.01; AP 2.7 to 2.2, p > 0.05). After pancreatic resection with planned IAT, AP resulted in failed isolations, lower yields, higher insulin requirements, poor long-term QOL improvement, and no improvement in pain scores compared with NAP. Further studies should define criteria for resection and IAT for patients with alcoholic chronic pancreatitis.


Transduction of fimbriation demonstrating common ancestry in FIRN strains of Salmonella typhimurium.
The production of fimbriate (Fim+) recombinants was observed in transductional crosses between different pairs of wild-type strains of different biotypes of Salmonella typhimurium. Fim+ recombinants were readily produced in transductions from Fim+ donor strains to Fim- recipient strains and, less frequently, between some pairs of Fim- strains, for example, between almost any strain of the firn biogroup (Fim- Inl- Rha- Bxyl-) and many strains of the non-FIRN Fim- biogroup. None of numerous crosses between different pairs of FIRN strains gave Fim+ recombinants, suggesting that the fim mutation was present at the same intragenic site in all FIRN strains. FIRN strains are thought to have descended from a single ancestral FIRN bacterium which originated by a series of mutations from a strain of the common biotype 1a (Fim+ Inl+ Rha+ Bxyl+). Two FIRN-like (Fim- Inl+ Rha- Bxyl-) strains that did not yield Fim+ recombinants in crosses with FIRN strains were probably wild-type Inl+ mutants from FIRN strains.


APOE ε2 is associated with increased tau pathology in primary tauopathy.
Apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset Alzheimer's disease mainly by modulating amyloid-β pathology. APOE ε4 is also shown to exacerbate neurodegeneration and neuroinflammation in a tau transgenic mouse model. To further evaluate the association of APOE genotype with the presence and severity of tau pathology, we express human tau via an adeno-associated virus gene delivery approach in human APOE targeted replacement mice. We find increased hyperphosphorylated tau species, tau aggregates, and behavioral abnormalities in mice expressing APOE ε2/ε2. We also show that in humans, the APOE ε2 allele is associated with increased tau pathology in the brains of progressive supranuclear palsy (PSP) cases. Finally, we identify an association between the APOE ε2/ε2 genotype and risk of tauopathies using two series of pathologically-confirmed cases of PSP and corticobasal degeneration. Our data together suggest APOE ε2 status may influence the risk and progression of tauopathy.


Community-based preventive activities in the Public Dental Service in Norway.
The purpose of this study was to describe community-based preventive interventions undertaken by the dental team outside the dental clinics in Norway, from the dental hygienists' and the dentists' perspective, with the main focus on target groups and existing guidelines and routines for these activities. A secondary aim was to identify the personnel responsible for developing the local guidelines and the knowledge sources for the guidelines. With the assistance of the Chief Dental Officers in 15 Public Dental Service (PDS) regions, questionnaires were emailed to the local clinics (n = 421). In each, the most experienced dental hygienist and dentist were asked to respond; 215 dentists and 166 and dental hygienists responded (60%). Almost 40% of the respondents reported that their clinic had guidelines on community-based activities conducted outside the clinics. Dental hygienists and local chief dentists were responsible for planning them. The main target groups were young children and the dependent elderly; the majority of the activities were carried out at child welfare centres and for personnel at nursing homes or for home care nurses. At the regional and local level, a more strategic and coordinated approach to the provision of community-based activities is needed, including assessment of oral health needs among population groups. Continuous documentation and evaluation of results are necessary for optimal use of available resources and to facilitate an evidence-based approach.


Nucleotide recognition by the initiation factor aIF5B: free energy simulations of a neoclassical GTPase.
The GTPase aIF5B is a universally conserved initiation factor that assists ribosome assembly. Crystal structures of its nucleotide complexes, X-ray(GTP) and X-ray(GDP), are similar in the nucleotide vicinity, but differ in the orientation of a distant domain IV. This has led to two, contradictory, mechanistic models. One postulates that X-ray(GTP) and X-ray(GDP) are, respectively, the active, "ON" and the inactive, "OFF" states; the other postulates that both structures are OFF, whereas the ON state is still uncharacterized. We study GTP/GDP binding using molecular dynamics and a continuum electrostatic free energy method. We predict that X-ray(GTP) has a ≈ 3 kcal/mol preference to bind GDP, apparently contradicting its assignment as ON. However, the preference arises mainly from a single, nearby residue from the switch 2 motif: Glu81, which becomes protonated upon GTP binding, with a free energy cost of about 4 kcal/mol. We then propose a different model, where Glu81 protonation/deprotonation defines the ON/OFF states. With this model, the X-ray(GTP):GTP complex, with its protonated Glu81, is ON, whereas X-ray(GTP):GDP is OFF. The model postulates that distant conformational changes such as domain IV rotation are "uncoupled" from GTP/GDP exchange and do not affect the relative GTP/GDP binding affinities. We analyze the model using a general thermodynamic framework for GTPases. It yields rather precise predictions for the nucleotide specificities of each state, and the state specificities of each nucleotide, which are roughly comparable to the homologues IF2 and aIF2, despite the lack of any conformational switching in the model.


[Relationship between the kininase- and angiotensin- converting activity under normal conditions and in experimental myocardial infarct].
In rat experiments the depressor and pressor responses to kinins and angiotensins recorded in the carotid artery were compared as to the different methods of their administration. With intravenous injection, the responses to bradykinin and kallidin were lower, and to angiotensin I--higher, than with their intra-aortic administration. The responses to angiotensin II remain identical under these conditions. The administration of all the preparations against the background of 2,3-dimercaptopropanol (unithiol) resulted in levelling of the responses irrespective of the mode of administration. In experimental myocardial infarction induced in rats by ligation of the coronary artery a reduction of the kinin-destructing and an increase of the angiotensin-converting activity was noted in the early postinfarction period. The response of the peripheral vessels to angiotensin, bradykinin and noradrenaline is decreased, while that to isoproterenol remain unchanged. The obtained results support the concept of the existence of the kininase and angiotensin-converting activity connected with a common biochemical factor of pulmonary circulation. Changes in the proportion of these functions under normal conditions and in cases of pathological states are interpreted as a particular regulation mechanism of the vascular tone and arterial pressure.


The Impact of Osteoarthritis on the Functioning and Health Status of a Low-Income Population: An Example of a Disability Paradox.
The aim of this study was to measure the impact of osteoarthritis on the functioning and health status of individuals living in a low-income urban community in Mexico. We conducted a cross-sectional, community-based study from December 2014 to November 2015, using the Community Oriented Program for Control of Rheumatic Diseases methodology to identify cases of musculoskeletal disease in a sample of adults older than 18 years in Pueblo Nuevo, Apodaca, Mexico. Two rheumatologists confirmed all cases of osteoarthritis (OA) using predefined criteria. Functioning was evaluated through (a) self-report of difficulty doing personal care, work, and leisure activities; (b) the modified Stanford Health Assessment Questionnaire-Disability Index; and (c) the Timed Up and Go test. Health status was evaluated using the EuroQoL 5 Dimensions. Statistical analyses were performed using χ tests and logistic regression models. Four hundred thirty-nine individuals with a mean age of 45.2 years were included, and 83 cases of OA were confirmed. The presence of OA was not significantly associated with having difficulties to do personal care, work, or leisure activities, but it was significantly associated with a higher Health Assessment Questionnaire-Disability Index score, longer time to complete the Timed Up and Go, and lower health status. Osteoarthritis is associated with having higher disability and worse health status in the community studied. A disability paradox was detected as some individuals perceived disability for doing standard activities but did not present disability performing their real-life activities. This underlies the importance of addressing the mental dimension during the management of this population.


eWaSR-An Embedded-Compute-Ready Maritime Obstacle Detection Network.
Maritime obstacle detection is critical for safe navigation of autonomous surface vehicles (ASVs). While the accuracy of image-based detection methods has advanced substantially, their computational and memory requirements prohibit deployment on embedded devices. In this paper, we analyze the current best-performing maritime obstacle detection network, WaSR. Based on the analysis, we then propose replacements for the most computationally intensive stages and propose its embedded-compute-ready variant, eWaSR. In particular, the new design follows the most recent advancements of transformer-based lightweight networks. eWaSR achieves comparable detection results to state-of-the-art WaSR with only a 0.52% F1 score performance drop and outperforms other state-of-the-art embedded-ready architectures by over 9.74% in F1 score. On a standard GPU, eWaSR runs 10× faster than the original WaSR (115 FPS vs. 11 FPS). Tests on a real embedded sensor OAK-D show that, while WaSR cannot run due to memory restrictions, eWaSR runs comfortably at 5.5 FPS. This makes eWaSR the first practical embedded-compute-ready maritime obstacle detection network. The source code and trained eWaSR models are publicly available.


Treatment methods for fractures of the mandibular angle.
Fractures of the mandibular angle are plagued with the highest rate of complication of all mandibular fractures. Over the past 8 years, the following six accepted forms of treatment for these fractures were performed on an indigent inner-city population: closed reduction or intra-oral open reduction and nonrigid fixation; extraoral open reduction and internal fixation with an AO/ASIF reconstruction bone plate; and intraoral open reduction and internal fixation using either two 2.0 mm minidynamic compression plates, two 2.4 mm mandibular dynamic compression plates, two noncompression miniplates, or a single noncompression miniplate. This article reviews the results of those treatment modalities when used for the same patient population at one hospital. Results show that the use of either an extraoral open reduction and internal fixation with the AO/ASIF reconstruction plate or intraoral open reduction and internal fixation using a single miniplate was associated with the fewest complications.


A proficiency-based orientation program for perioperative nurses.
One of the primary responsibilities of staff development in the operating room is developing and implementing a comprehensive orientation and assessment program for nurse orientees. This orientation program must be relevant to both the nurse's and the hospital's needs. It must also meet the requirements of accreditation agencies. Proficiency Requirements for Entry-Level Perioperative Practice, a proficiency-based orientation program, meets those needs in a cost effective and simple manner.


Electrostatic evaluation of the signature motif (H/V)CX5R(S/T) in protein-tyrosine phosphatases.
The catalytic activity of protein-tyrosine phosphatases (PTPs) is mediated by a cysteine side chain which carries out a nucleophilic attack initiating the phosphate cleavage. Experimentally, it has been observed that the active site cysteine has a remarkably low pKa. In the present study, we have investigated the origin of the low pKa by analyzing the electrostatic properties of four different protein-tyrosine phosphatases: Yersinia PTP (bacteria), PTP1B (human), VHR (human), and low molecular weight phosphatase (bovine). These phosphatases have very low sequence homology and show very low structural similarity. However, they share a common active site motif [the (H/V)CX5R(S/T) sequence] which adopts a unique loop structure. We have applied the so-called single site titration method, which is based on the Poisson-Boltzmann methodology, to (i) study the influence of the architecture of the (H/V)CX5R(S/T) loop on the pKa of the active cysteine and (ii) examine which parts of the active site region stabilize the ionized form of the cysteine. Our results indicate that the architecture of the (H/V)CX5R(S/T) loop has a major impact on the low pKa of the active cysteines. The orientation of the microdipoles generated by the partial charges of the backbone atoms (i.e., the CONHCalpha atoms) is essential for maintaining the low pKa. Further, the electrostatic field generated by these microdipoles has a larger impact than the electrostatic dipole generated by the central alpha-helix. Interactions of the active cysteine with other ionizable side chains play a minor role in stabilizing the thiolate anion. The only ionizable side chain significantly influencing the pKa of the active site cysteine is the arginine, which is an important part of the consensus sequence.


Genetic Variation in 9p21 and the Plasma Proteome.
Single nucleotide polymorphisms (SNPs) in the noncoding region of 9p21 have been associated with cardiovascular disease (CVD), but the mechanisms by which these genetic variants contribute to the pathogenesis of CVD remain unknown since no annotated proteins are present in this region of DNA. The objective of the current study was to determine if 9p21 genotypes are associated with distinct plasma proteins in young adults. Subjects were 1611 young adults aged 20-29 years from the Toronto Nutrigenomics and Health Study (1098 females and 513 males). DNA was isolated from fasting blood to analyze four SNPs in 9p21 (rs2383206, rs10757274, rs10757278, and rs1333049). Abundant plasma proteins ( n = 54) were measured using liquid chromatography multiple reaction monitoring mass spectrometry. Analysis of covariance was used to determine differences in plasma proteins between genotypes. In Caucasians ( n = 524), four SNPs were associated with apolipoprotein E and two with haptoglobin-β-chain concentration. In East Asians ( n = 388), three SNPs were associated with α-1b-Glycoprotein, two with apolipoprotein B-100, one with apolipoprotein E and one with haptoglobin-β-chain concentration. In South Asians ( n = 117), one SNP was associated with apolipoprotein B-100 concentration. Our findings suggest that 9p21 genotypes may play a role in various pathophysiological pathways that contribute to risk of CVD in early adulthood that might be distinct among different ethnocultural groups.


Understanding Compound, Interconnected, Interacting, and Cascading Risks: A Holistic Framework.
In recent years, there has been a gradual increase in research literature on the challenges of interconnected, compound, interacting, and cascading risks. These concepts are becoming ever more central to the resilience debate. They aggregate elements of climate change adaptation, critical infrastructure protection, and societal resilience in the face of complex, high-impact events. However, despite the potential of these concepts to link together diverse disciplines, scholars and practitioners need to avoid treating them in a superficial or ambiguous manner. Overlapping uses and definitions could generate confusion and lead to the duplication of research effort. This article gives an overview of the state of the art regarding compound, interconnected, interacting, and cascading risks. It is intended to help build a coherent basis for the implementation of the Sendai Framework for Disaster Risk Reduction (SFDRR). The main objective is to propose a holistic framework that highlights the complementarities of the four kinds of complex risk in a manner that is designed to support the work of researchers and policymakers. This article suggests how compound, interconnected, interacting, and cascading risks could be used, with little or no redundancy, as inputs to new analyses and decisional tools designed to support the implementation of the SFDRR. The findings can be used to improve policy recommendations and support tools for emergency and crisis management, such as scenario building and impact trees, thus contributing to the achievement of a system-wide approach to resilience.


International eDelphi Study to Reach Consensus on the Methotrexate Dosing Regimen in Patients With Psoriasis.
A clear dosing regimen for methotrexate in psoriasis is lacking, and this might lead to a suboptimal treatment. Because methotrexate is affordable and globally available, a uniform dosing regimen could potentially optimize the treatment of patients with psoriasis worldwide. To reach international consensus among psoriasis experts on a uniform dosing regimen for treatment with methotrexate in adult and pediatric patients with psoriasis and identify potential future research topics. Between September 2020 and March 2021, a survey study with a modified eDelphi procedure that was developed and distributed by the Amsterdam University Medical Center and completed by 180 participants worldwide (55 [30.6%] resided in non-Western countries) was conducted in 3 rounds. The proposals on which no consensus was reached were discussed in a conference meeting (June 2021). Participants voted on 21 proposals with a 9-point scale (1-3 disagree, 4-6 neither agree nor disagree, 7-9 agree) and were recruited through the Skin Inflammation and Psoriasis International Network and European Academy of Dermatology and Venereology in June 2020. Apart from being a dermatologist/dermatology resident, there were no specific criteria for participation in the survey. The participants worked mainly at a university hospital (97 [53.9%]) and were experienced in treating patients with psoriasis with methotrexate (163 [91.6%] had more than 10 years of experience). In a survey with eDelphi procedure, we tried to reach consensus on 21 proposals. Consensus was defined as less than 15% voting disagree (1-3). For the consensus meeting, consensus was defined as less than 30% voting disagree. Of 251 participants, 180 (71.7%) completed all 3 survey rounds, and 58 participants (23.1%) joined the conference meeting. Consensus was achieved on 11 proposals in round 1, 3 proposals in round 2, and 2 proposals in round 3. In the consensus meeting, consensus was achieved on 4 proposals. More research is needed, especially for the proposals on folic acid and the dosing of methotrexate for treating subpopulations such as children and vulnerable patients. In this eDelphi consensus study, consensus was reached on 20 of 21 proposals involving methotrexate dosing in patients with psoriasis. This consensus may potentially be used to harmonize the treatment with methotrexate in patients with psoriasis.


Colocalization of glycolytic enzyme activity and KATP channels in basolateral membrane of Necturus enterocytes.
86Rb fluxes through ATP-regulated K+ (KATP) channels in membrane vesicles derived from basolateral membranes of Necturus small intestinal epithelial cells as well as the activity of single KATP channels reconstituted into planar phospholipid bilayers are inhibited by the presence of ADP plus phosphoenolpyruvate in the solution bathing the inner surface of these channels. This inhibition can be prevented by pretreatment of the membranes with 2, 3-butanedione, an irreversible inhibitor of pyruvate kinase (PK) and reversed by the addition of 2-deoxyglucose plus hexokinase. The results of additional studies indicate that PK activity appears to be tightly associated with this membrane fraction. These results, together with considerations of the possible ratio of Na+-K+ pumps to KATP channels in the basolateral membrane, raise the possibility that "cross talk" between those channels and pumps (i.e., the "pump-leak parallelism") may be mediated by local, functionally compartmentalized ATP-to-ADP ratios that differ from those in the bulk cytoplasm.


Toluene Diisocyanate Exposure: Exposure Assessment and Development of Cross-Facility Similar Exposure Groups Among Toluene Diisocyanate Production Plants.
The objective of this study was to characterize workplace toluene diisocyanate (TDI) exposures using standardized industrial hygiene exposure assessment procedures for use in a prospective epidemiologic study of occupational asthma. Over 2300 representative routine full shift time-weighted average (TWA) and short-term high potential exposure tasks (HPETs) air samples in groups across three TDI plants were collected over a nearly 7-year period. Data-derived similar exposure groups (SuperSEGs) were developed across the plants based on TWA sampling using cluster analysis. Individual cumulative exposure estimates were developed on the basis of the SuperSEGs. Workplace TWA exposures to TDI were adequately characterized quantitatively, but HPET exposures were adequately characterized only by qualitative measures. The mean TWA exposure was 0.65 parts per billion for 1594 routine samples. These TWA and HPET exposures can be used to support exposure-response analyses.


c-Jun NH2-terminal kinase/c-Jun signaling promotes survival and metastasis of B lymphocytes transformed by Theileria.
Theileria parasites infect and transform bovine lymphocytes resulting in tumors with metastatic/invasive potential. Importantly, cellular transformation is reversed upon drug-induced parasite death, and the infected lymphocyte dies of apoptosis within 48 hours. Theileria-dependent transformation leads to the constitutive activation of c-Jun NH2-terminal kinase (both JNK1 and JNK2) and permanent induction of activator protein-1. Inactivation of JNK (following transfection of dominant-negative mutants, or treatment with a JNK-specific inhibitor) leads to lymphocyte apoptosis, suggesting an antiapoptotic role for JNK activation in Theileria-induced B cell transformation. Theileria-induced JNK activation also leads to constitutive c-Jun phosphorylation, and inhibition of c-Jun and activator protein-1 transactivation following the expression of a dominant-negative mutant of c-Jun sensitizes Theileria-transformed B cells to apoptosis, but does not significantly affect their proliferation. Thus, JNK activation and c-Jun induction have overlapping, but nonidentical antiapoptotic roles in Theileria-induced B cell transformation. Increased sensitivity to apoptosis may be related to the fact that the expression levels of antiapoptotic proteins such as Mcl-1 and c-IAP are reduced upon c-Jun inhibition. In addition, decreased c-Jun expression correlates with the impaired ability of transfected B cells to degrade synthetic matrix in vitro, and their injection into lymphoid mice gives rise to significantly less and smaller tumors. Combined, these data argue for a role for JNK and c-Jun induction in the survival and metastasis of Theileria-transformed B cells. The similarity between Theileria-transformed B cells with human B lymphomas argues that exploiting the reversible nature of Theileria-induced transformation could throw light on the mechanisms underlying human malignancies.


Promoter methylation and Ile105val polymorphism of GSTP1 gene in the modulation of colorectal cancer risk in ethnic Kashmiri population.
Glutathione-S-transferases (GSTs) are the most important phase II enzymes of the xenobiotic pathway responsible for the detoxification of carcinogens. GSTP1 gene polymorphisms are mostly associated with a lack or an alteration of enzymatic activity toward several substrates thus resulting in increased cancer susceptibility. GSTP1 promoter methylation is also frequently associated with tumor development or poor prognosis in a wide range of tumors. In this study, we examined the role of genetic polymorphism and promoter methylation of GSTP1 gene in the context of modulation of risk of colorectal cancer (CRC) in Kashmiri population. This study used tissue tumor samples (114) and blood samples from (160) patients with CRC and 200 blood samples from healthy donors. GSTP1 polymorphism was studied using polymerase chain reaction (PCR)-restriction fragment length polymorphism and methylation using methylation-specific PCR. There was no significant association between GSTP1 I105V genotypes and the CRC (P>0.05). However, we found a significant association of the Val/Val variant genotype with the dwelling and smoking status (P-value < 0.05). Overall, the homozygous variant Val/Val genotype was associated with a modestly elevated risk for CRC (OR = 1.57; 95% CI = 0.67-3.57). Methyl-specific-PCR analysis revealed 25.4% methylation of the GSTP1 promoter in CRC cases and was not found to be statistically significantly associated with clinicopathological parameters of the CRC cases (P>0.05). Also, no significant associations of any of the three genotypes with promoter hypermethylation were observed. We conclude that promoter hypermethylation in homozygous GSTP1 mutants did not elevate the risk of CRC in Kashmiri population.


Pediatric brain arteriovenous malformation recurrence: a cohort study, systematic review and meta-analysis.
Recurrence following obliteration of brain arteriovenous malformations (AVMs) is common in children surgically treated, but recurrences following endovascular (EVT) and radiosurgical approaches are scantily reported. To analyze the rates and risk factors for AVM recurrence after obliteration in a single-center cohort of children with ruptured AVMs treated with multimodal approaches, and to carry out a comprehensive review and meta-analysis of current data. Children with ruptured AVMs between 2000 and 2019 enrolled in a prospective registry were retrospectively screened and included after angiographically determined obliteration to differentiate children with/without recurrence. A complementary systematic review and meta-analysis of studies investigating AVM recurrence in children between 2000 and 2020 was aggregated to explore the overall recurrence rates across treatment modalities by analyzing surgery versus other treatments. Seventy children with obliterated AVMs were included. AVM recurrences (n=10) were more commonly treated with EVT as final treatment (60% in the recurrence vs 13.3% in the no-recurrence group, p=0.018). Infratentorial locations were associated with earlier and more frequent recurrences (adjusted relative risk=4.62, 95% CI 1.08 to 19.04; p=0.04).In the aggregate analysis, the pooled rate of AVM recurrence was 10.9% (95% CI 8.7% to 13.5%). Younger age at presentation was associated with more frequent recurrences (RR per year increase, 0.97, 95% CI 0.93 to 0.99; p=0.046). Location of infratentorial AVMs and younger age at presentation may be associated with earlier and more frequent recurrences. The higher rates of recurrence in patients with AVMs obliterated with EVT questions its role in an intent-to-cure approach and reinforces its position as an adjunct to surgery and/or radiosurgery.


The dynamic structure of Rab35 is stabilized in the presence of GTP under physiological conditions.
Rab proteins, a family of small guanosine triphosphatases, play key roles in intracellular membrane trafficking and the regulation of various cellular processes. As a Rab isoform, Rab35 is crucial for recycling endosome trafficking, cytokinesis and neurite outgrowth. In this report, we analyzed dynamic structural changes and physicochemical features of Rab35 in response to different external conditions, including temperature, pH, salt concentration and guanosine triphosphate (GTP), by circular dichroism (CD) spectroscopy. CD spectra revealed that the α-helix content of Rab35 varies under different conditions considerably. The addition of GTP increases the α-helix content of Rab35 when the temperature, pH and salt concentration match physiological conditions. The results suggest that the external environment affects the secondary structure of Rab35. In particular, the presence of GTP stabilized the α-helices of Rab35 under physiological conditions. These structural changes may translate to changes in Rab35 function and relate to its role in membrane trafficking.


Association between micronucleus frequency and cervical intraepithelial neoplasia grade in Thinprep cytological test and its significance.
A micronucleus is an additional small nucleus formed due to chromosomes or chromosomal fragments fail to be incorporated into the nucleus during cell division. In this study, we assessed the utility of micronucleus counting as a screening tool in cervical precancerous lesions in Thinprep cytological test smears under oil immersion. High risk HPV was also detected by hybrid capture-2 in Thinprep cytological test smears. Our results showed that micronucleus counting was significantly higher in high-grade squamous intraepithelial lesion (HSIL) and invasive carcinoma cases compared to low-grade squamous intraepithelial lesion (LSIL) and non-neoplastic cases. Receiver operating characteristic (ROC) curve analysis revealed that micronucleus counting possessed a high degree of sensitivity and specificity for identifying HSIL and invasive carcinoma. Cut-off of 7.5 for MN counting gave a sensitivity of 89.6% and a specificity of 66.7% (P = 0.024 and AUC = 0.892) for detecting HSIL and invasive carcinoma lesions. Multiple linear regression analysis showed that only HSIL and invasive cancer lesions not age, duration of marital life and number of pregnancy are significantly associated with MN counting. The positive rate of high risk HPV was distinctly higher in LSIL, HSIL and invasive cancer than that in non-neoplstic categories. In conclusions, MN evaluation may be viewed as an effective biomarker for cervical cancer screening. The combination of MN count with HPV DNA detection and TCT may serve as an effective means to screen precancerous cervical lesions in most developing nations.


Effect of Home Care Nursing on Patients Discharged From Hospital With Self-Reported Signs of Constipation: A Randomized Trial.
Constipation is a common health problem in relation to hospitalization. This randomized controlled trial aimed to investigate whether advice from a home care nurse after discharge had an effect on self-reported signs of constipation. A total of 59 patients were included in the study on the basis of their self-reported signs of constipation evaluated using the Constipation Assessment Scale. Advice from the home care nurses was given on the intake of fiber and liquid and mobilization related to scorings on the Constipation Risk Assessment Scale, the administration of laxatives, and referral to a physician when needed. Results showed a tendency toward the visits being effective, but a more complex intervention might be needed.


A genetic predictive model for canine hip dysplasia: integration of Genome Wide Association Study (GWAS) and candidate gene approaches.
Canine hip dysplasia is one of the most prevalent developmental orthopedic diseases in dogs worldwide. Unfortunately, the success of eradication programs against this disease based on radiographic diagnosis is low. Adding the use of diagnostic genetic tools to the current phenotype-based approach might be beneficial. The aim of this study was to develop a genetic prognostic test for early diagnosis of hip dysplasia in Labrador Retrievers. To develop our DNA test, 775 Labrador Retrievers were recruited. For each dog, a blood sample and a ventrodorsal hip radiograph were taken. Dogs were divided into two groups according to their FCI hip score: control (A/B) and case (D/E). C dogs were not included in the sample. Genetic characterization combining a GWAS and a candidate gene strategy using SNPs allowed a case-control population association study. A mathematical model which included 7 SNPs was developed using logistic regression. The model showed a good accuracy (Area under the ROC curve = 0.85) and was validated in an independent population of 114 dogs. This prognostic genetic test represents a useful tool for choosing the most appropriate therapeutic approach once genetic predisposition to hip dysplasia is known. Therefore, it allows a more individualized management of the disease. It is also applicable during genetic selection processes, since breeders can benefit from the information given by this test as soon as a blood sample can be collected, and act accordingly. In the authors' opinion, a shift towards genomic screening might importantly contribute to reducing canine hip dysplasia in the future. In conclusion, based on genetic and radiographic information from Labrador Retrievers with hip dysplasia, we developed an accurate predictive genetic test for early diagnosis of hip dysplasia in Labrador Retrievers. However, further research is warranted in order to evaluate the validity of this genetic test in other dog breeds.


Response of nitrogen metabolism in lettuce plants subjected to different doses and forms of selenium.
Currently, biofortification programmes are being carried out with selenium (Se), since it is an essential element for humans and its ingestion depends partly on a vegetable diet, this not being so for plants. In this sense, few studies have tested the effect that Se has on some of the main plant metabolisms, such as nitrogen (N) metabolism. Thus the aim of this study was to establish the effect of the application of different doses (5, 10, 20, 40, 60, 80 and 120 micromol L(-1)) and forms (selenate and selenite) of Se on the reduction of nitrate (NO3-) and subsequent assimilation of ammonium (NH4+). The results showed an increase in all enzyme activities analysed (nitrate reductase (NR), nitrite reductase (NiR), glutamine synthetase (GS) and glutamate synthase (GOGAT)), especially with application of the selenite form, in addition to a decline in foliar NO3- concentration. Se applied in both forms increased N metabolism, with selenite inducing this physiological process more strongly, since it prompted a stronger activation of NR, GS and GOGAT as well as a greater concentration of total reduced N.


Evaluation of the male reproductive toxicity of gallium arsenide.
Gallium arsenide is an important semiconductor material marketed in the shape of wafers and thus is not hazardous to the end user. Exposure to GaAs particles may, however, occur during manufacture and processing. Potential hazards require evaluation. In 14-week inhalation studies with small GaAs particles, testicular effects have been reported in rats and mice. These effects occurred only in animals whose lungs showed marked inflammation and also had hematologic changes indicating anemia and hemolysis. The time- and concentration-dependent progressive nature of the lung and blood effects together with bioavailability data on gallium and arsenic lead us to conclude that the testicular/sperm effects are secondary to hypoxemia resulting from lung damage rather than due to a direct chemical effect of gallium or arsenide. Conditions leading to such primary effects are not expected to occur in humans at production and processing sites. This has to be taken into consideration for any classification decision for reproductive toxicity; especially a category 1 according to the EU CLP system is not warranted.


Plantar heel pain in middle-aged and older adults: population prevalence, associations with health status and lifestyle factors, and frequency of healthcare use.
The objectives of this study were to estimate the population prevalence and distribution of plantar heel pain in mid-to-older age groups, examine associations with selected health status and lifestyle factors, and report the frequency of healthcare use. Adults aged ≥50 years registered with four general practices were mailed a health survey (n = 5109 responders). Plantar heel pain in the last month was defined by self-reported shading on a foot manikin, and was defined as disabling if at least one of the function items of the Manchester Foot Pain and Disability Index were also reported. Population prevalence estimates and associations between plantar heel pain and demographic characteristics, health status measures and lifestyle factors were estimated using multiple imputation and weighted logistic regression. Healthcare professional consultation was summarised as the 12-month period prevalence of foot pain-related consultation. The population prevalence of plantar heel pain was 9.6% (95% CI: 8.8, 10.5) and 7.9% (7.1, 8.7) for disabling plantar heel pain. Occurrence was slightly higher in females, comparable across age-groups, and significantly higher in those with intermediate/routine and manual occupations. Plantar heel pain was associated with physical and mental impairment, more anxiety and depression, being overweight, a low previous use of high-heeled footwear, and lower levels of physical activity and participation. The 12-month period prevalence of foot pain-related consultation with a general practitioner, physiotherapist or podiatrist/chiropodist was 43.0, 15.1 and 32.8%, respectively. Plantar heel pain is a common, disabling symptom among adults aged 50 years and over. Observed patterns of association indicate that in addition to focused foot-specific management, primary care interventions should also target more general physical and psychological factors that could potentially act as barriers to treatment adherence and recovery.


Air pollution-regulated E-cadherin mediates contact inhibition of proliferation via the hippo signaling pathways in emphysema.
Air pollution has been linked to emphysema in chronic obstruction pulmonary disease (COPD). However, the underlying mechanisms in the development of emphysema due to air pollution remain unclear. The objective of this study was to investigate the role of components of the Hippo signaling pathway for E-cadherin-mediated contact inhibition of proliferation in the lungs after air pollution exposure. E-Cadherin-mediated contact inhibition of proliferation via the Hippo signaling pathway was investigated in Sprague-Dawley (SD) rats whole-body exposed to air pollution, and in alveolar epithelial A549 cells exposed to diesel exhaust particles (DEPs), E-cadherin-knockdown, and high-mobility group box 1 (HMGB1) treatment. Underlying epithelial differentiation, apoptosis, and senescence were also examined, and the interaction network among these proteins was examined. COPD lung sections were used to confirm the observations in rats. Expressions of HMGB1 and E-cadherin were negatively regulated in the lungs and A549 cells by air pollution, and this was confirmed by knockdown of E-cadherin and by treating A549 cells with HMGB1. Depletion of phosphorylated (p)-Yap occurred after exposure to air pollution and E-cadherin-knockdown, which resulted in decreases of SPC and T1α. Exposure to air pollution and E-cadherin-knockdown respectively downregulated p-Sirt1 and increased p53 levels in the lungs and in A549 cells. Moreover, the protein interaction network suggested that E-cadherin is a key activator in regulating Sirt1 and p53, as well as alveolar epithelial cell differentiation by SPC and T1α. Consistently, downregulation of E-cadherin, p-Yap, SPC, and T1α was observed in COPD alveolar regions with particulate matter (PM) deposition. In conclusion, our results indicated that E-cadherin-mediated cell-cell contact directly regulates the Hippo signaling pathway to control differentiation, cell proliferation, and senescence due to air pollution. Exposure to air pollution may initiate emphysema in COPD patients.


Variation in Septoria musiva and Implications for Disease Resistance Screening of Poplars.
A set of isolates of Septoria musiva differed in aggressiveness in hybrid poplar leaf disk and stem assays and culture growth in vitro. Clone × isolate interactions were observed in one of the stem assay experiments, but not in the leaf disk assay experiments. Random amplified polymorphic DNA (RAPD) analyses were performed using 52 isolates of S. musiva collected from hybrid poplars and a native poplar species in Minnesota, Wisconsin, Iowa, South Dakota, and North Dakota. There was a large degree of genetic similarity, although each isolate had a unique RAPD pattern. No relationships among isolates were found for molecular genetic distance and host clone, parentage, or taxonomic classification section; location or date of collection; or the previously determined level of field resistance of the host clones to Septoria canker. Results of the stem and leaf disk assays indicate that it may not be necessary to choose the most aggressive isolate for disease resistance screening. It may be more useful to select isolates that will discriminate the greatest variation in levels of disease resistance among the clones that are being screened.


Different Policy Measures and Practices between Swedish Counties Influence Market Dynamics: Part 1-Biosimilar and Originator Infliximab in the Hospital Setting.
Decentralisation of healthcare budgets and issuance of local guidelines means that the use of biosimilars can vary by region within a particular country, for example between the 21 counties of Sweden. This study aimed to analyse the county-level market dynamics of biosimilar and originator infliximab, which are hospital products, and to examine how local policy measures and practices, in addition to national policy, influenced market dynamics. We first conducted a literature review on (biosimilar) policies in Sweden, then analysed market data provided by IQVIA™ on uptake of originator and biosimilar infliximab within the different counties (Q2 2012 to Q4 2017), including discounts from (tender) contracts. Biosimilar market shares were calculated with volume data (measured as defined daily doses [DDDs]). We then discussed our findings in semi-structured interviews with the national pricing and reimbursement agency, key experts within the county councils of Skåne, Västra Götaland, and Stockholm, and an industry representative. Market shares of biosimilar infliximab vary widely between counties (range 18-96% in 2017). The initial uptake of biosimilar infliximab was slow and variable, with abrupt increments in biosimilar market shares coinciding with expiration of contracts for the originator product. Different approaches taken by counties to achieve a low cost per DDD of infliximab were identified, i.e., a rapid switch to the biosimilar (Skåne), a delayed switch to the biosimilar (Stockholm), or no switch to the biosimilar when a favourable price on the originator product could be obtained (Västra Götaland). Quantitative analysis showed that 59% of the variability in biosimilar market shares could be explained by the relative difference in discounted price between the biosimilar and the originator product. In addition, qualitative analysis indicated the presence of key opinion leaders, local guidelines and initiatives, and whose budget it affects as drivers in the decision-making process. Variations in the market share of biosimilar infliximab between the Swedish counties is largely explained by the discounted price difference between biosimilar and originator product, and counties used different strategies to leverage such biosimilar competition. Additionally, the presence of key opinion leaders, local guidelines and gainsharing arrangements appeared to play a role in infliximab market dynamics in counties.


THE POTENTIAL INDICATOR VALUE OF RARE TAXA RICHNESS IN DIATOM-BASED STREAM BIOASSESSMENT1.
Despite their recognized contribution to species richness, the importance of rare taxa richness in bioassessment is unclear. This study aimed to characterize the environmental factors affecting the number of rare diatom taxa in western U.S. streams and rivers, and to evaluate whether this number can be used to differentiate streams with contrasting human disturbance. Three different categories of rare taxa were used: satellite (taxa with low occurrence and low abundance), rural (taxa with high occurrence and low abundance), and urban (taxa with low occurrence and high abundance). Common taxa were included as a separate category of core taxa (taxa with high occurrence and high abundance). We analyzed 987 diatom samples collected over the period of 5 years (2000-2004) for the U.S. Environmental Protection Agency's (EPA) Western Environmental Monitoring and Assessment Program (WEMAP). The results showed that rural taxa richness (number of rural taxa per site) increased along a longitudinal gradient from mountainous, fast-flowing oligotrophic streams with fewer fine substrates to large, slow-moving, nutrient-rich rivers with abundance of fine substrates. Rural taxa richness was the only rarity metric that distinguished least disturbed (reference) sites from the most disturbed (impacted) sites, but it was significantly different only in the mountains ecoregion. Core taxa richness distinguished reference from impacted sites in the West and in each one of the three ecoregions (mountains, plains, and xeric). Our findings revealed that rural taxa richness can be used as an indicator of human disturbance in streams/rivers, especially in the mountains ecoregion, and that rarity definition is important in bioassessment.


Individual and family predictors of the perpetration of dating violence and victimization in late adolescence.
Teen dating violence is a crime of national concern with approximately one-fourth of adolescents reporting victimization of physical, psychological, or sexual dating violence each year. The present study examined how aggressive family dynamics in both childhood and early adolescence predicted the perpetration of dating violence and victimization in late adolescence. Children (n = 401, 43 % female) were followed from kindergarten entry to the age of 18 years. Early adolescent aggressive-oppositional problems at home and aggressive-oppositional problems at school each made unique predictions to the emergence of dating violence in late adolescence. The results suggest that aggressive family dynamics during childhood and early adolescence influence the development of dating violence primarily by fostering a child's oppositional-aggressive responding style initially in the home, which is then generalized to other contexts. Although this study is limited by weaknesses detailed in the discussion, the contribution of longitudinal evidence including parent, teacher, and adolescent reports from both boys and girls, a dual-emphasis on the prediction of perpetration and victimization, as well as an analysis of both relations between variables and person-oriented group comparisons combine to make a unique contribution to the growing literature on adolescent partner violence.


Nitrous oxide (laughing gas) is an NMDA antagonist, neuroprotectant and neurotoxin.
Extensive research has failed to clarify the mechanism of action of nitrous oxide (N2O, laughing gas), a widely used inhalational anesthetic and drug of abuse. Other general anesthetics are thought to act by one of two mechanisms-blockade of NMDA glutamate receptors or enhancement of GABAergic inhibition. Here we show that N2O, at anesthetically-relevant concentrations, inhibits both ionic currents and excitotoxic neurodegeneration mediated through NMDA receptors and, like other NMDA antagonists, produces neurotoxic side effects which can be prevented by drugs that enhance GABAergic inhibition. The favorable safety record of N2O may be explained by the low concentrations typically used and by the fact that it is usually used in combination with GABAergic anesthetics that counteract its neurotoxic potential.


Simulation and the future of military medicine.
The U.S. military currently faces serious difficulties in training medical personnel in peacetime for the tasks of war. The military beneficiary population comprises fit young service men and women, their dependents, and retirees. Their peacetime care, although vital, does little to prepare military medical personnel for war. Medical commanders have instituted an array of training programs to compensate for this shortfall, but there remains a large gap between operational medical needs and training opportunities in peacetime. The military has begun to examine whether simulation can fill this gap. An array of commercial, off-the-shelf technologies are already being used with varying degrees of success, and major initiatives are under way in both academia and industry, supported by the military, to develop virtual reality products for combat medical training. Even as the military exploits emerging technology and begins to articulate a simulation strategy, there is a growing interest in civilian medicine in the potential for simulation to affect patient safety--how medical simulation might mitigate the injuries and deaths caused by medical errors--and how it might also improve the quality of medical education and training.


[Prenatal action of tetracycline hydrochloride on lymph node development in the rat].
Histological and morphological methods were used to study the ante- and postnatal development of tracheobronchial and mesenterial nodes of white rats exposed to tetracycline in the preimplantation period (days 1-6 of the embryogenesis), during placentation and early organogenesis (days 8-13), and in the late organogenesis (days 14-19). Administration of tetracycline on days 1-6 and 8-13 of the embryogenesis disturbs the formation of the morphofunctional structures of the node, inhibits the lympho- and plasmocytopoiesis associated with a dramatic increase in the number of granulocytes and mast cells. Exposure to the antibiotic on days 14-19 of the embryo-genesis does not impair the formation of the lymph nodes but leads to an increase in them of the number of lymphocytes, plasmocytes, macrophages, eosinophilic granulocytes and mast cells.


Comparing the efficacies of alginate, foam, hydrocolloid, hydrofiber, and hydrogel dressings in the management of diabetic foot ulcers and venous leg ulcers: a systematic review and meta-analysis examining how to dress for success.
Diabetic foot ulcers and venous leg ulcers are chronic wounds frequently encountered by dermatologists. Choosing appropriate wound dressings can effectively promote wound healing and potentially reduce morbidity and financial burden experienced by patients. The objective of our systematic review and meta-analysis was to evaluate wound healing efficacies of synthetic active dressings in diabetic foot ulcer and venous leg ulcer management. For data collection, PubMed, Embase, Cochrane Library, CINAHL, and clinicaltrials.gov online databases were searched from database inception to 10 May 2015. Fixed and random effects modeling were used to calculate pooled risk ratios for complete ulcer healing from pairwise dressing comparisons. The results of our review showed moderate-quality level evidence that hydrogels were more effective in healing diabetic foot ulcers than basic wound contact dressings (RR 1.80 [95% CI, 1.27-2.56]). The other dressing comparisons showed no statistically significant differences between the interventions examined in terms of achieving complete diabetic foot ulcer healing. Non-adherent dressings were more cost-effective than hydrofiber dressings for diabetic foot ulcers in terms of mean total cost per patient of the dressings themselves. All venous leg ulcer pairwise dressing comparisons showed equivalent dressing efficacies in terms of promoting complete ulcer healing. Overall, most synthetic active dressings and traditional wound dressings are equally efficacious in treating diabetic foot ulcers and venous leg ulcers. For treating diabetic foot ulcers, hydrogels are more efficacious than basic wound contact dressings, and non-adherent dressings are more cost-effective than hydrofiber dressings. Ultimately, dressing choice should be tailored to the wound and the patient.


Amyand's hernia.
We present vermiform appendix finding within an inguinal hernia sac, rare pathology, well-known as Amyand's hernia. We relate the incidence in the literature and the recommended conducts.


Telehealth amid the COVID-19 pandemic: perception among Asian, Native Hawaiian and Pacific Islander cancer patients.
Aim: To assess the perception of telehealth visits among a multiracial cancer population during the coronavirus disease 2019 pandemic. Methods: This cross-sectional study was conducted at outpatient cancer clinics in Hawaii between March and August 2020. Patients were invited to participate in the survey either by phone or email. Results: Of the 212 survey respondents, 61.3% were Asian, 23.6% were White and 15.1% were Native Hawaiians or Pacific Islanders. Asians, Native Hawaiians and Pacific Islanders were less likely to desire future telehealth visits compared with Whites. Predictors with regard to preferring future telehealth visits included lower income and hematopoietic cancers. Conclusion: The authors found racial differences in preference for telehealth. Future studies aimed at overcoming these racial disparities are needed to provide equitable oncology care.


Contrast-assisted destruction-replenishment ultrasound for the assessment of tumor microvasculature in a rat model.
Angiogenesis, the development of new blood vessels, is necessary for tumor growth. Anti-angiogenic therapies have recently received attention as a possible cancer treatment. The purpose of this study was to monitor the vascularity of induced tumors in rats using contrast-enhanced ultrasound during anti-angiogenic therapy. Six rats with subcutaneously implanted R3230 murine mammary adenocarcinomas were treated with an orally administered anti-angiogenic agent (SU11657) beginning 28 days after tumor implantation (20 mg/kg BW once daily). Three additional tumor-bearing control rats were treated with an equivalent volume of vehicle alone. Sonographic evaluation of tumor blood flow was performed using a modified Siemens Sonoline Elegra equipped with a 5.0 MHz linear transducer prior to drug administration, during the first 51 hours following initial drug administration, and on days 8 and 15 after initiation of therapy. Tumor volumes were estimated at each time point using a prolate ellipsoid method from linear dimensions measured on the B-mode ultrasound image in the three major axes. A destruction-replenishment technique was used for tumor blood flow evaluation using a constant rate infusion of intravenously delivered ultrasound contrast media (Definity). A destructive pulse was fired first, followed by a chain of non-destructive pulses that allowed for visualization of vascular contrast agent replenishment. Parametric maps of the time required for contrast agent replenishment and the time-integrated intensity were generated for both the tumor and kidney. Following ultrasound examination, contrast-enhanced computed tomography of each tumor was performed in the same imaging plane as that used to acquire the ultrasound images. Fifteen days after the start of treatment, tumors were excised, preserved in 10% formalin, and sectioned in a plane approximating the ultrasound and CT imaging planes. Sections were prepared for light microscopy with H & E, CD31 and factor VIII immunostain to evaluate overall morphology and vessel distribution. Ultrasound measurements of tumor volume, the spatial extent of contrast enhancement, and the time required for contrast replenishment within control tumors were significantly different from those of treated tumors. The time-integrated ultrasound contrast enhancement decreases and the time required for replenishment of the contrast agent within the tumor volume increases over the course of anti-angiogenic therapy. Parametric maps of integrated intensity are shown to correlate with the regions of viable tumor demonstrated on H & E and regions of elevated contrast intensity on CT. Contrast-enhanced ultrasound imaging of implanted tumors provides a tool to assess differences in the microcirculation of treated and control tumors in studies of anti-angiogenic agents.


Feasibility of the homogeneous head model in the interpretation of neuromagnetic fields.
During the past few years it has been demonstrated that active areas in the human brain can be located by measuring the magnetic fields arising from the electric currents in the neurons. An established model for the conductivity geometry of the head in these studies is the layerwise homogeneous sphere. If, however, the measurement grid is too large or the local radius of curvature of the head is changing rapidly in the measurement area, this simple model may become inadequate. In this paper we investigate the feasibility of replacing the conducting sphere by a homogeneous body having the shape of the brain. We show by a semi-quantitative argument that the homogeneous body model is justified. A numerical procedure for the calculation of the magnetic field is presented with examples of the accuracy that can be obtained. An example of significant differences between the predictions of the homogeneous and sphere models is discussed.


Identifying infants at risk for sudden infant death syndrome.
This review examines recent research relevant to the underlying pathophysiology and risk factors for sudden infant death syndrome. Current research focuses on the linkage between known risk factors and vulnerability, genetic contributions, and the role of dysfunctional brainstem neurotransmission in the pathogenesis of this syndrome. While social inequalities, prematurity, maternal smoking, infant sleeping practices and sleep environment, arousal failures and environmental pollutants remain important risk factors, new evidence is emerging that certain genetic polymorphisms may contribute to vulnerability. New neuropathological studies have provided strong support for abnormal brainstem serotonergic function. Since serotonin influences a wide range of physiological systems including breathing, the cardiovascular system, temperature, and sleep-wake cycles, this finding strongly supports the hypothesis that sudden infant death syndrome is the result of dysregulation of the autonomic nervous system and provides biological plausibility for certain risk reduction strategies. Despite a putative diagnostic shift, sudden infant death syndrome remains the most common cause of death from 1 month to 1 year of age. Recent studies confirmed established risk factors and have suggested new genetic vulnerabilities. Finally, new evidence supports a key role for abnormalities in brainstem serotonin systems in the pathophysiology of this syndrome.


Axitinib after Sunitinib in Metastatic Renal Cancer: Preliminary Results from Italian "Real-World" SAX Study.
Axitinib is an oral angiogenesis inhibitor, currently approved for treatment of metastatic renal cell carcinoma (mRCC) after failure of prior treatment with Sunitinib or cytokine. The present study is an Italian Multi-Institutional Retrospective Analysis that evaluated the outcomes of Axitinib, in second-line treatment of mRCC. The medical records of 62 patients treated with Axitinib, were retrospectively reviewed. The Progression Free Survival (PFS), the Overall Survival (OS), the Objective Response Rate (ORR), the Disease Control Rate (DCR), and the safety profile of axitinib and sunitinib-axitinib sequence, were the primary endpoint. The mPFS was 5.83 months (95% CI 3.93-7.73 months). When patients was stratified by Heng score, mPFS was 5.73, 5.83, 10.03 months according to poor, intermediate, and favorable risk group, respectively. The mOS from the start of axitinib was 13.3 months (95% CI 8.6-17.9 months); the observed ORR and DCR were 25 and 71%, respectively. When stratified patients by subgroups defined by duration of prior therapy with Sunitinib (≤ vs. >median duration), there was a statistically significant difference in mPFS with 8.9 (95% CI 4.39-13.40 months) vs. 5.46 months (95% CI 4.04-6.88 months) for patients with a median duration of Sunitinib >13.2 months. DCR and ORR to previous Sunitinib treatment was associated with longer statistically mPFS, 7.23 (95% CI 3.95-10.51 months, p = 0.01) and 8.67 (95% CI 4.0-13.33 months, p = 0.008) vs. 2.97 (95% CI 0.65-5.27 months, p = 0.01) and 2.97 months (95% CI 0.66-5.28 months, p = 0.01), respectively. Overall Axitinib at standard schedule of 5 mg bid, was well-tolerated. The most common adverse events of all grades were fatig (25.6%), hypertension (22.6%), gastro-intestinal disorders (25.9%), and hypothyroidism (16.1%). The sequence Sunitinib-Axitinib was well-tolerated without worsening in side effects, with a median OS of 34.7 months (95% CI 18.4-51.0 months). Our results are consistent with the available literature; this retrospective analysis confirms that Axitinib is effective and safe in routine clinical practice.


Rapid reduction and removal of HDL- but not LDL-associated cholesteryl ester hydroperoxides by rat liver perfused in situ.
To test whether high-density lipoproteins (HDL) could aid in the removal in vivo of potentially atherogenic oxidized lipids, we perfused rat liver in situ with buffer supplemented with isolated human HDL containing small amounts of cholesteryl linoleate hydro(pero)xides [CH18:2-O(O)H]. Perfusion resulted in the rapid removal of Ch18:2-O(O)H from HDL with a half-life (t1/2)of 11.4 min., faster than that of unoxidized cholesteryl linoleate, and dependent of the presence of the liver. In addition, the liver enhanced the reduction of Ch18:2-OOH associated with HDL remaining in the perfusate buffer. Perfusion resulted in the release of a hepatic activity that enhanced the reduction of HDL-associated CH18:2-OOH and was resistant to heat treatment. In contrast with the situation with HDL, low-density lipoprotein (LDL)-associated CH18:2-O(O)H were neither removed nor reduced by perfused rat liver within the time course studied, in support of a possible role for HDL in the detoxification of circulating lipid hydroperoxides in vivo.


Optimal Prediction of Carotid Intraplaque Hemorrhage Using Clinical and Lumen Imaging Markers.
MR imaging detects intraplaque hemorrhage with high accuracy by using the magnetization-prepared rapid acquisition of gradient echo sequence. Still, MR imaging is not readily available for all patients, and many undergo CTA instead. Our goal was to determine essential clinical and lumen imaging predictors of intraplaque hemorrhage, as indicators of its presence and clues to its pathogenesis. In this retrospective cross-sectional study, patients undergoing stroke work-up with MR imaging/MRA underwent carotid intraplaque hemorrhage imaging. We analyzed 726 carotid plaques, excluding vessels with non-carotid stroke sources (n = 420), occlusions (n = 7), or near-occlusions (n = 3). Potential carotid imaging predictors of intraplaque hemorrhage included percentage diameter and millimeter stenosis, plaque thickness, ulceration, and intraluminal thrombus. Clinical predictors were recorded, and a multivariable logistic regression model was fitted. Backward elimination was used to determine essential intraplaque hemorrhage predictors with a thresholded 2-sided P < .10. Receiver operating characteristic analysis was also performed. Predictors of carotid intraplaque hemorrhage included plaque thickness (OR = 2.20, P < .001), millimeter stenosis (OR = 0.46, P < .001), ulceration (OR = 4.25, P = .020), age (OR = 1.11, P = .001), and male sex (OR = 3.23, P = .077). The final model discriminatory value was excellent (area under the curve = 0.932). This was significantly higher than models using only plaque thickness (area under the curve = 0.881), millimeter stenosis (area under the curve = 0.830), or ulceration (area under the curve= 0.715, P < .001). Optimal discrimination of carotid intraplaque hemorrhage requires information on plaque thickness, millimeter stenosis, ulceration, age, and male sex. These factors predict intraplaque hemorrhage with high discriminatory power and may provide clues to the pathogenesis of intraplaque hemorrhage. This model could be used to predict the presence of intraplaque hemorrhage when MR imaging is contraindicated.


Bioenergetics of photoheterotrophic bacteria in the oceans.
Photoheterotrophic microbes, such as proteorhodopsin (PR)-based phototrophic (PRP) and aerobic anoxygenic phototrophic (AAP) bacteria, are well known to be abundant in the oceans, potentially playing unique roles in biogeochemical cycles. However, the contribution of phototrophy to the energy requirements of these bacteria has not been quantitatively examined to date. To better understand the implications of photoheterophy in the oceans, we calculated energy benefits and costs of phototrophy and compared net benefits with maintenance costs. Benefits depend on the number of photosynthetic units (PSUs), absorption cross-section area of each PSU as function of wavelength, the in situ light quality, and the energy yield per absorbed photon. For costs we considered the energy required for the synthesis of pigments, amino acids and proteins in each PSU. Our calculations indicate that AAP bacteria harvest more light energy than do PRP bacteria, but the costs of phototrophy are much higher for AAP bacteria. Still, the net energy gained by AAP bacteria is often sufficient to meet maintenance costs, while that is not the case for PRP bacteria except with high light intensities and large numbers of proteorhodopsin molecules per cell. The low costs and simplicity of PR-based phototrophy explain the high abundance of proteorhodopsin genes in the oceans. However, even for AAP bacteria, the net energy yield of phototrophy is apparently too low to influence the distribution of photoheterotrophic bacteria among various marine systems.


Lick-shock contingencies in the rat.
Hungry rats were allowed to lick an 8% sucrose solution and then one of four lick-shock contingency conditions was superimposed on the licking baseline. These conditions were: free-operant avoidance, free shock, punishment, and no shock. From highest to lowest response rates, the groups fell in the order-avoidance, no shock, free shock, and punishment. Lick rates adjusted rapidly to introduction and removal of the contingencies. Post-shock responding was lowest in the punishment condition and highest in the free shock condition. No method was found simultaneously to equate shock frequency and separate response rates for the three shock contingency conditions. Only small, or no, reductions in shock rate occurred over sessions under the free-operant avoidance schedule when the shock-shock interval was 10 sec but large reductions occurred when the shock-shock interval was reduced to either 1 or 2 sec.


Liver X receptor β and peroxisome proliferator-activated receptor δ regulate cholesterol transport in murine cholangiocytes.
Nuclear receptors (NRs) play crucial roles in the regulation of hepatic cholesterol synthesis, metabolism, and conversion to bile acids, but their actions in cholangiocytes have not been examined. In this study, we investigated the roles of NRs in cholangiocyte physiology and cholesterol metabolism and flux. We examined the expression of NRs and other genes involved in cholesterol homeostasis in freshly isolated and cultured murine cholangiocytes and found that these cells express a specific subset of NRs, including liver X receptor (LXR) β and peroxisome proliferator-activated receptor (PPAR) δ. Activation of LXRβ and/or PPARδ in cholangiocytes induces ATP-binding cassette cholesterol transporter A1 (ABCA1) and increases cholesterol export at the basolateral compartment in polarized cultured cholangiocytes. In addition, PPARδ induces Niemann-Pick C1-like L1 (NPC1L1), which imports cholesterol into cholangiocytes and is expressed on the apical cholangiocyte membrane via specific interaction with a peroxisome proliferator-activated response element (PPRE) within the NPC1L1 promoter. We propose that (1) LXRβ and PPARδ coordinate NPC1L1/ABCA1-dependent vectorial cholesterol flux from bile through cholangiocytes and (2) manipulation of these processes may influence bile composition with important applications in cholestatic liver disease and gallstone disease, two serious health concerns for humans.


Dual effects of isoflavonoids from Pueraria lobata roots on estrogenic activity and anti-proliferation of MCF-7 human breast carcinoma cells.
Pueraria lobata root (PLR), well known as Kudzu root, has recently become commercially available in Western dietary supplements for menopausal symptoms. The scientific basis for its action has been attributed to the action of phytoestrogens. This study aimed to investigate the estrogen-like activity of isoflavonoids isolated from P. lobata root and their safety with respect to their effect on breast cancer cell proliferation. In an E-screen assay, crude MeOH extract of PLR significantly increased the proliferation of MCF-7 cells in a concentration-dependent manner. Among the four fractions obtained by solvent fractionation of MeOH extract, the n-BuOH fraction had significant estrogen-like activities at all concentrations tested. Phytochemical analysis of the n-BuOH fraction led to the isolation of 10 isoflavones (1-10), among which genistein (10) had significant estrogen-like activities at all concentrations tested. These activities were significantly enhanced by treatment with genistein and 17β-estradiol compared with 17β-estradiol alone, and this effect was mediated by decreased expression of estrogen receptor (ER)α and phospho-ERα in MCF-7 cells. In a cell cytotoxicity assay, genistein (10) exhibited significant cytotoxicity in both ER-positive MCF-7 and ER-negative MDA-MB-231 breast cancer cells. This cytotoxicity was characterized by the induction of apoptotic cells stained with annexin V conjugated with Alexa Fluor 488 and involved activation of mitochondria-independent and -dependent apoptosis pathways in MCF-7 cells. Our results demonstrated that genistein (10) has estrogen-like effects dependent on ER pathway activation and anti-proliferative effects mediated by the apoptosis pathway rather than the ER pathway in MCF-7 breast cancer cells.


Weight and economic development: current net nutrition in the late 19th- and early 20th-century United States.
When traditional measures for material and economic welfare are scarce or unreliable, height and the body mass index (BMI) are now widely accepted measures that represent cumulative and current net nutrition in development studies. However, as the ratio of weight to height, BMI does not fully isolate the effects of current net nutrition. After controlling for height as a measure for current net nutrition, this study uses the weight of a sample of international men in US prisons. Throughout the late 19th- and early-20th centuries, individuals with darker complexions had greater weights than individuals with fairer complexions. Mexican and Asian populations in the US had lower weights and reached shorter statures. Black and white weights stagnated throughout the late 19th- and early-20th centuries. Agricultural workers' had greater weights than workers in other occupations.


The implication of irrigation in climate change impact assessment: a European-wide study.
This study evaluates the impacts of projected climate change on irrigation requirements and yields of six crops (winter wheat, winter barley, rapeseed, grain maize, potato, and sugar beet) in Europe. Furthermore, the uncertainty deriving from consideration of irrigation, CO2 effects on crop growth and transpiration, and different climate change scenarios in climate change impact assessments is quantified. Net irrigation requirement (NIR) and yields of the six crops were simulated for a baseline (1982-2006) and three SRES scenarios (B1, B2 and A1B, 2040-2064) under rainfed and irrigated conditions, using a process-based crop model, SIMPLACE <LINTUL5, DRUNIR, HEAT>. We found that projected climate change decreased NIR of the three winter crops in northern Europe (up to 81 mm), but increased NIR of all the six crops in the Mediterranean regions (up to 182 mm yr(-1) ). Climate change increased yields of the three winter crops and sugar beet in middle and northern regions (up to 36%), but decreased their yields in Mediterranean countries (up to 81%). Consideration of CO2 effects can alter the direction of change in NIR for irrigated crops in the south and of yields for C3 crops in central and northern Europe. Constraining the model to rainfed conditions for spring crops led to a negative bias in simulating climate change impacts on yields (up to 44%), which was proportional to the irrigation ratio of the simulation unit. Impacts on NIR and yields were generally consistent across the three SRES scenarios for the majority of regions in Europe. We conclude that due to the magnitude of irrigation and CO2 effects, they should both be considered in the simulation of climate change impacts on crop production and water availability, particularly for crops and regions with a high proportion of irrigated crop area.


Effect of methanethiol on process performance, selectivity and diversity of sulfur-oxidizing bacteria in a dual bioreactor gas biodesulfurization system.
This study provides important new insights on how to achieve high sulfur selectivities and stable gas biodesulfurization process operation in the presence of both methanethiol and H2S in the feed gas. On the basis of previous research, we hypothesized that a dual bioreactor lineup (with an added anaerobic bioreactor) would favor sulfur-oxidizing bacteria (SOB) that yield a higher sulfur selectivity. Therefore, the focus of the present study was to enrich thiol-resistant SOB that can withstand methanethiol, the most prevalent and toxic thiol in sulfur-containing industrial off gases. In addition, the effect of process conditions on the SOB population dynamics was investigated. The results confirmed that thiol-resistant SOB became dominant with a concomitant increase of the sulfur selectivity from 75 mol% to 90 mol% at a loading rate of 2 mM S methanethiol day-1. The abundant SOB in the inoculum - Thioalkalivibrio sulfidiphilus - was first outcompeted by Alkalilimnicola ehrlichii after which Thioalkalibacter halophilus eventually became the most abundant species. Furthermore, we found that the actual electron donor in our lab-scale biodesulfurization system was polysulfide, and not the primarily supplied sulfide.


Reduced fibre size, capillary supply and mitochondrial activity in constitutional thinness' skeletal muscle.
Constitutional thinness (CT) is a rare condition of natural low body weight, with no psychological issues, no marker of undernutrition and a resistance to weight gain. This study evaluated the skeletal muscle phenotype of CT women by comparison with a normal BMI control group. Ten CT women (BMI < 17.5 kg/m2 ) and 10 female controls (BMI: 18.5-25 kg/m2 ) underwent metabolic and hormonal assessment along with muscle biopsies to analyse the skeletal muscular fibres pattern, capillarity, enzymes activities and transcriptomics. Constitutional thinness displayed similar energy balance metabolic and hormonal profile to controls. Constitutional thinness presented with lower mean area of all the skeletal muscular fibres (-24%, P = .01) and percentage of slow-twitch type I fibres (-25%, P = .02, respectively). Significant downregulation of the mRNA expression of several mitochondrial-related genes and triglycerides metabolism was found along with low cytochrome c oxidase (COX) activity and capillary network in type I fibres. Pre- and post-mitochondrial respiratory chain enzymes levels were found similar to controls. Transcriptomics also revealed downregulation of cytoskeletal-related genes. Diminished type I fibres, decreased mitochondrial and metabolic activity suggested by these results are discordant with normal resting metabolic rate of CT subjects. Downregulated genes related to cytoskeletal proteins and myocyte differentiation could account for CT's resistance to weight gain.


High versus low positive end-expiratory pressure (PEEP) levels for mechanically ventilated adult patients with acute lung injury and acute respiratory distress syndrome.
Mortality in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) remains high. These patients require mechanical ventilation, but this modality has been associated with ventilator-induced lung injury. High levels of positive end-expiratory pressure (PEEP) could reduce this condition and improve patient survival. To assess the benefits and harms of high versus low levels of PEEP in patients with ALI and ARDS. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, 2013, Issue 4), MEDLINE (1950 to May 2013), EMBASE (1982 to May 2013), LILACS (1982 to May 2013) and SCI (Science Citation Index). We used the Science Citation Index to find references that have cited the identified trials. We did not specifically conduct manual searches of abstracts of conference proceedings for this review. We also searched for ongoing trials (www.trialscentral.org; www.clinicaltrial.gov and www.controlled-trials.com). We included randomized controlled trials that compared the effects of two levels of PEEP in ALI and ARDS participants who were intubated and mechanically ventilated in intensive care for at least 24 hours. Two review authors assessed the trial quality and extracted data independently. We contacted investigators to identify additional published and unpublished studies. We included seven studies that compared high versus low levels of PEEP (2565 participants). In five of the studies (2417 participants), a comparison was made between high and low levels of PEEP with the same tidal volume in both groups, but in the remaining two studies (148 participants), the tidal volume was different between high- and low-level groups. We saw evidence of risk of bias in three studies, and the remaining studies fulfilled all criteria for adequate trial quality.In the main analysis, we assessed mortality occurring before hospital discharge only in those studies that compared high versus low PEEP with the same tidal volume in both groups. With the three studies that were included, the meta-analysis revealed no statistically significant differences between the two groups (relative risk (RR) 0.90, 95% confidence interval (CI) 0.81 to 1.01), nor was any statistically significant difference seen in the risk of barotrauma (RR 0.97, 95% CI 0.66 to 1.42). Oxygenation was improved in the high-PEEP group, although data derived from the studies showed a considerable degree of statistical heterogeneity. The number of ventilator-free days showed no significant difference between the two groups. Available data were insufficient to allow pooling of length of stay in the intensive care unit (ICU). The subgroup of participants with ARDS showed decreased mortality in the ICU, although it must be noted that in two of the three included studies, the authors used a protective ventilatory strategy involving a low tidal volume and high levels of PEEP. Available evidence indicates that high levels of PEEP, as compared with low levels, did not reduce mortality before hospital discharge. The data also show that high levels of PEEP produced no significant difference in the risk of barotrauma, but rather improved participants' oxygenation to the first, third, and seventh days. This review indicates that the included studies were characterized by clinical heterogeneity.


Brain states in freely behaving marmosets.
We evaluated common marmosets as a perspective animal model to study human sleep and wake states. Using wireless neurologger recordings, we performed longitudinal multichannel local field potential (LFP) cortical, hippocampal, neck muscle, and video recordings in three freely behaving marmosets. The brain states were formally identified using self-organizing maps. Marmosets were generally awake during the day with occasional 1-2 naps, and they slept during the night. Major electrographic patterns fall in five clearly distinguished categories: wakefulness, drowsiness, light and deep NREM sleep, and REM. Marmosets typically had 14-16 sleep cycles per night, with either gradually increasing or relatively low, but stable delta power within the cycle. Overall, the delta power decreased throughout the night sleep. Marmosets demonstrated prominent high amplitude somatosensory mu-rhythm (10-15 Hz), accompanied with neocortical ripples, and alternated with occipital alpha rhythm (10-15 Hz). NREM sleep was characterized with the presence of high amplitude slow waves, sleep spindles and ripples in neocortex, and sharp-wave-ripple complexes in CA1. Light and deep stages differed in levels of delta and sigma power and muscle tone. REM sleep was defined with low muscle tone and activated LFP with predominant beta-activity and rare spindle-like or mu-like events. Multiple features of sleep-wake state distribution and electrographic patterns associated with behavioral states in marmosets closely match human states, although marmoset have shorter sleep cycles. This demonstrates that marmosets represent an excellent model to study origin of human electrographical rhythms and brain states.


Are the brain's vascular and Alzheimer pathologies additive or interactive?
Alzheimer's disease and cerebrovascular disease (CVD) commonly co-occur. Whether CVD promotes the progression of Alzheimer's disease pathology remains a source of great interest. Recent technological developments have enabled us to examine their inter-relationship using quantifiable, biomarker-based approaches. We provide an overview of advances in understanding the relationship between vascular and Alzheimer's disease pathologies, with particular emphasis on β-amyloid and tau as measured by positron emission tomography and cerebrospinal fluid (CSF) concentration, and magnetic resonance imaging markers of small vessel disease (SVD). The relationship between cerebral β-amyloid and various markers of SVD has been widely studied, albeit with somewhat mixed results. Significant associations have been elucidated, particularly between β-amyloid burden and white matter hyperintensities (WMH), as well as lobar cerebral microbleeds (CMB), with additive effects on cognition. There is preliminary evidence for an association between SVD and tau burden in vivo, although compared with β-amyloid, fewer studies have examined this relationship. The overlap between Alzheimer's disease and cerebrovascular pathologies is now being increasingly supported by imaging and CSF biomarkers, indicating a synergistic effect of these co-pathologies on cognition. The association of WMH and CMB with Alzheimer's disease pathology does not establish direction of causality, for which long-term longitudinal studies are needed.


Comparative Field Evaluation of Different Traps for Collecting Adult Phlebotomine Sand Flies (Diptera: Psychodidae) in an Endemic Area of Cutaneous Leishmaniasis in Quintana Roo, Mexico.
Phlebotominae are the vectors of Leishmania parasites. It is important to have available surveillance and collection methods for the sand fly vectors. The objectives of the present study were to evaluate and compare traps for the collection of sand fly species and to analyze trap catches along months and transects. Field evaluations over a year were conducted in an endemic area of leishmaniasis in the state of Quintana Roo, Mexico. A randomized-block design was implemented in study area with tropical rainforest vegetation. The study design utilized 4 transects with 11 trap types: 1) Centers for Disease Control and Prevention (CDC) light trap with incandescent bulb (CDC-I), 2) CDC light trap with blue light-emitting diodes (LEDs) (CDC-B), 3) CDC light trap with white LEDs (CDC-W), 4) CDC light trap with red LEDs (CDC-R), 5) CDC light trap with green LEDs (CDC-G), 6) Disney trap, 7) Disney trap with white LEDs, 8) sticky panels, 9) sticky panels with white LEDs, 10) delta-like trap, and 11) delta-like trap with white LEDs. A total of 1,014 specimens of 13 species and 2 genera (Lutzomyia and Brumptomyia) were collected. There were significant differences in the mean number of sand flies caught with the 11 traps; CDC-I was (P = 0.0000) more effective than the other traps. Other traps exhibited the following results: CDC-W (17.46%), CDC-B (15.68%), CDC-G (14.89%), and CDC-R (14.30%). The relative abundance of different species varied according to trap types used, and the CDC-I trap attracted more specimens of the known vectors of Leishmania spp., such as like Lutzomyia cruciata, Lu. shannoni, and Lu. ovallesi. Disney trap captured more specimens of Lu. olmeca olmeca. Based on abundance and number of species, CDC light traps and Disney traps appeared to be good candidates for use in vector surveillance programs in this endemic area of Mexico.


Knockdown of protein tyrosine phosphatase receptor U inhibits growth and motility of gastric cancer cells.
Protein tyrosine phosphatase receptor U (PTPRU) has been shown to be a tumor suppressor in colon cancer by dephosphorylating β-catenin and reducing the activation of β-catenin signaling. Here, we investigate the expression of PTPRU protein in gastric cancer cell lines, gastric cancer tissues and respective adjacent non-cancer tissues and find that the 130 kDa nuclear-localized PTPRU fragment is the main PTPRU isoform in gastric cancer cells, whereas the full-length PTPRU is relatively lowly expressed. The level of the 130 kDa PTPRU is higher in gastric cancer tissues than in adjacent non-cancer tissues. Knockdown of endogenous PTPRU in gastric cancer cells using lentivirus-delivered specific shRNA results in the attenuation of cell growth, migration, invasion and adhesion. Knockdown of PTPRU also inhibits tyrosine phosphorylation and transcriptional activity of β-catenin as well as levels of focal adhesion proteins and lysine methylation of histone H3. These results indicate that PTPRU is required for gastric cancer progression and may serve as a potential therapeutic target.


Loss of function of Ribonuclease T2, an ancient and phylogenetically conserved RNase, plays a crucial role in ovarian tumorigenesis.
In recent years, the role played by the stromal microenvironment has been given growing attention in order to achieve a full understanding of cancer initiation and progression. Because cancer is a tissue-based disease, the integrity of tissue architecture is a major constraint toward cancer growth. Indeed, a large contribution of the natural resistance to cancer stems from stromal microenvironment components, the dysregulation of which can facilitate cancer occurrence. For instance, recent experimental evidence has highlighted the involvement of stromal cells in ovarian carcinogenesis, as epitomized by ovarian xenografts obtained by a double KO of the murine Dicer and Pten genes. Likewise, we reported the role of an ancient extracellular RNase, called Ribonuclease T2 (RNASET2), within the ovarian stromal microenvironment. Indeed, hyperexpression of RNASET2 is able to control tumorigenesis by recruiting macrophages (mostly of the anticancer M1 subtype) at the tumor sites. We present biological data obtained by RNASET2 silencing in the poorly tumorigenetic and highly RNASET2-expressing human OVCAR3 cell line. RNASET2 knockdown was shown to stimulate in vivo tumor growth early after microinjection of OVCAR3 cells in nude mice. Moreover, we have investigated by molecular profiling the in vivo expression signature of human and mouse cell xenografts and disclosed the activation of pathways related to activation of the innate immune response and modulation of ECM components. Finally, we provide evidence for a role of RNASET2 in triggering an in vitro chemotactic response in macrophages. These results further highlight the critical role played by the microenvironment in RNASET2-mediated ovarian tumor suppression, which could eventually contribute to better clarify the pathogenesis of this disease.