The impact of long-term warfarin therapy on quality of life. Evidence from a randomized trial. Boston Area Anticoagulation Trial for Atrial Fibrillation Investigators.
To determine the effect of long-term warfarin sodium therapy on quality of life, we surveyed 333 patients participating in a randomized, controlled trial of warfarin for the prevention of stroke in nonrheumatic atrial fibrillation. No significant differences between warfarin-treated and control patients were found on well-validated measures of functional status, well-being, and health perceptions. For example, the summary score for health perceptions was 68.8 in the warfarin-treated vs 66.6 in the control group (scale of 0 to 100; 95% confidence intervals for the difference, -1.6 to 6.0). In contrast, patients taking warfarin who had a bleeding episode had a significant decrease in health perceptions (-11.9; 95% confidence interval, -4.1 to -19.6). Warfarin therapy is not usually associated with a significant decrease in perceived health, unless a bleeding episode has occurred. Negative effects of warfarin treatment on health perceptions may be balanced by confidence in its protective effects.


Technical Note - Lateral Approach to the Lumbar Spine for the Removal of Interbody Cages.
Revision surgery to address the migration or fracture of a lumbar interbody cage can be technically challenging. Scar tissue and fibrosis, among other anatomic barriers, can make removal of the cage a complicated procedure, potentially increasing postoperative pain as well as the probability of neurologic deficits. Use of the lateral surgical technique for removal of the cage can avoid these potential complications. In this case report, we describe the removal of interbody cages through a lateral approach in three patients without the necessity of additional posterior hardware revision.


The impact of market-based 'reform' on cultural values in health care.
The many issues managed care poses for providers and health networks are crystallized in the moral problems occasioned by its shifting of the financial risks of care from insurer to provider. The issues occasioned by market-based reform include: the problems presented by clashes between public expectations and payer restrictions; the corporatization of health service delivery and the cultural shift from humanitarian endeavor to business enterprise the depersonalization of treatment as time and money constraints stretch resources, and the culture rewards efficient "business-like" behavior the underfunding of care for the poor and uninsured, even as these populations grow the restructuring of care and reengineering of healthcare roles as the emphasis shifts from quality of care to conservation of resources rapid mergers of both health plans and institutional providers with all the inherent turmoil as rules change, services are eliminated, and support services are minimized to save money the unhealthy competition inherent in market-based reform that posits profit taking and market share as the measures of successful performance the undermining of the professional ethic of advocacy the use of incentives that pander to greed and self-interest. The costs of sophisticated technologies and the ongoing care of increasingly fragile patients have pulled many other elements into what previously were considered "privileged" professional interactions. The fact that very few citizens indeed could pay out-of-pocket for the treatment and ongoing care they might need led to social involvement (few people remember that both widespread health insurance and public programs are relatively recent phenomena--only about 30 years old). However, whether in tax dollars or insurance premiums, other people's money is being spent on the patient's care. Clearly, those "other people" never intended to give either the patient or the professional open-ended access to their collective pocketbooks. Just what form their involvement ought to take is being tested as "managed care" attempts to control the costs. What limits are acceptable to providers?: lower profit margins? quality controls? acceptable risk levels? To patients?: restricted choice? restricted mobility? restricted access to high tech? And to the general public?: decreased access to high tech? higher taxes? underserved populations? Abandonment of the sick or poor? Which "techniques" are acceptable, and which are not?: risk-sharing with providers? financial incentives for decision makers? rationing access? imposing behavioral parameters? The issues posed by market-based managed care cannot be adequately addressed merely in terms of social resources, nor will answers be found in subordinating human rights to practical materialism. Negotiating ethical guidelines for the "safe" handling of such problems to the good of individuals and of society requires a revitalization of the "old" values: the old commitment to master craftsmanship and altruism, the old emphasis on patient advocacy and human rights. However, these old values must be applied with the "new" knowledge of lifestyle choices (and thus personal responsibility), likely outcomes (and thus reasonable options), and the limits of success (and thus fair redeployment of health resources).


The extent and specificity of visual exploration determines the formation of recollected memories in complex scenes.
Our visual memories of complex scenes often appear as robust, detailed records of the past. Several studies have demonstrated that active exploration with eye movements improves recognition memory for scenes, but it is unclear whether this improvement is due to stronger feelings of familiarity or more detailed recollection. We related the extent and specificity of fixation patterns at encoding and retrieval to different recognition decisions in an incidental memory paradigm. After incidental encoding of 240 real-world scene photographs, participants (N = 44) answered a surprise memory test by reporting whether an image was new, remembered (indicating recollection), or just known to be old (indicating familiarity). To assess the specificity of their visual memories, we devised a novel report procedure in which participants selected the scene region that they specifically recollected, that appeared most familiar, or that was particularly new to them. At encoding, when considering the entire scene,subsequently recollected compared to familiar or forgotten scenes showed a larger number of fixations that were more broadly distributed, suggesting that more extensive visual exploration determines stronger and more detailed memories. However, when considering only the memory-relevant image areas, fixations were more dense and more clustered for subsequently recollected compared to subsequently familiar scenes. At retrieval, the extent of visual exploration was more restricted for recollected compared to new or forgotten scenes, with a smaller number of fixations. Importantly, fixation density and clustering was greater in memory-relevant areas for recollected versus familiar or falsely recognized images. Our findings suggest that more extensive visual exploration across the entire scene, with a subset of more focal and dense fixations in specific image areas, leads to increased potential for recollecting specific image aspects.


[Epidemiology of reno-ureteral lithiasis in the province of Toledo].
In this paper a review is made of a total of 384 patients suffering from lithiasic illness and the authors stress the high incidence of hyperuricuria in the province of Toledo, referring to the possible effect and cause link between this type of lithiasis and an unsuitable diet. On the other hand, they find no connection between this type of lithiasis and the chemical-mineral composition of the water as a possible contributory, lithogenetic factor.


Tuberculosis in greater kudu.
Four greater kudu (Tragelaphus strepsiceros) died while maintained in captivity at a zoo. Necropsy revealed tuberculous lesions in the lungs, spleen, and thoracic lymph nodes. Histopathologic findings included granulomas with Langhans' giant cells, necrosis, and mineralization. Acid-fast organisms isolated from tissues of each kudu were identified as Mycobacterium bovis.


CircAFF2 Promotes Neuronal Cell Injury in Intracerebral Hemorrhage by Regulating the miR-488/CLSTN3 Axis.
Intracerebral hemorrhage (ICH), a subtype of devastating stroke, carries high morbidity and mortality worldwide. CircRNA AFF2 (circAFF2) was significantly increased in ICH patients, but the underlying mechanism of circAFF2 is unknown. Hemin was employed to treat neuronal cells to mimic ICH in vitro. Mice were injected with collagenase VII-S to establish in vivo ICH models. Genes and protein expressions were detected using qRT-PCR and Western blotting. The interaction among circAFF2, miR-488, and CLSTN3 was validated by dual-luciferase reporter assay and RNA-RIP. Cell viability, MDA, iron, GSH, and lipid ROS were examined using the MTT, the commercial kits, and flow cytometry, respectively. ICH injury in mice was evaluated using neurological deficit scores and brain water measurements. CircAFF2 was significantly increased in ICH in vivo and in vitro models. CircAFF2 bound to miR-488 and knockdown of circAFF2 or overexpression of miR-488 inhibited hemin-induced injury of neuronal cells as indicated by increased cell viability and reduced markers of oxidative stress and lipid peroxidation. CLSTN3 was the downstream target of miR-488. Silencing of circAFF2 or miR-488 overexpression reduced CLSTN3 expression and protected against the injury of neuronal cells. In vivo experiments finally confirmed that circAFF2 knockdown attenuated mice ICH injury via the miR-488/CLSTN3 axis. CircAFF2 promotes the injury of neuronal cells and exacerbates ICH via increasing CLSTN3 by sponging miR-488, suggesting that circAFF2 may be a potential therapeutic target for ICH treatment.


Association of Psychosocial Symptoms, Blood Pressure, and Menopausal Status in African-American Women.
African-American women have disproportionate rates of hypertension that can be further complicated as they transition through menopause. Stress, coupled with depression and hypertension in perimenopausal African-American women has not been fully explored. This study examines the associations of stress, depression, and social support on systolic blood pressure (SBP) among a sample of 184 perimenopausal African-American women. We used descriptive statistics, Pearson's correlation, and logistic regression to analyze data stratified by menopausal status (perimenopausal or menopausal) and SBP status (<130 mmHg vs. >130 mmHg). Women classified as menopausal reported higher levels of stress and depressive symptoms, and lower levels of social support. Age, body mass index (BMI), health insurance, and perceived health status were significant predictors of SBP in menopausal women. Stress, depression, and social support did not play a role in SBP. It is necessary that future research focus on reducing cardiovascular risk include addressing menopausal health.


Gut mucosal cells transfer α-synuclein to the vagus nerve.
Epidemiological and histopathological findings have raised the possibility that misfolded α-synuclein protein might spread from the gut to the brain and increase the risk of Parkinson's disease. Although past experimental studies in mouse models have relied on gut injections of exogenous recombinant α-synuclein fibrils to study gut-to-brain α-synuclein transfer, the possible origins of misfolded α-synuclein within the gut have remained elusive. We recently demonstrated that sensory cells of intestinal mucosa express α-synuclein. Here, we employed mouse intestinal organoids expressing human α-synuclein to observe the transfer of α-synuclein protein from epithelial cells in organoids to cocultured nodose neurons devoid of α-synuclein. In mice expressing human α-synuclein, but no mouse α-synuclein, α-synuclein fibril-templating activity emerged in α-synuclein-seeded fibril aggregation assays in intestine, vagus nerve, and dorsal motor nucleus. In newly engineered transgenic mice that restrict pathological human α-synuclein expression to intestinal epithelial cells, α-synuclein fibril-templating activity transfered to the vagus nerve and dorsal motor nucleus. Subdiaphragmatic vagotomy prior to induction of α-synuclein expression in intestinal epithelial cells effectively protected the hindbrain from emergence of α-synuclein fibril-templating activity. Overall, these findings highlight a potential non-neuronal source of fibrillar α-synuclein protein that might arise in gut mucosal cells.


[Cost-utility analysis as a mechanism for allocation of health care resources: a review of the debate].
Priority setting in health care involves choosing between alternative health care programs and/or patients or groups of patients who will receive care. Traditionally, health economists have proposed maximizing the additional health gain measured in QALYs as a way of setting priorities and maximizing social welfare. This requires that the social value from health improvements be a product of gains in years of life, quality of life, and number of people treated. The results of a literature review suggest that potential health gain is not a single relevant determinant of value, nor is the rule of maximizing this gain sufficient. The social value of a health gain appears not to be linear in terms of mortality and morbidity, or neutral vis-à-vis people's characteristics or the ultimate distribution of health in society. In parallel with the review of the debate on the role and limitation of QALYs for prioritizing health care resources, the article attempts to justify the controversy over some empirical results, particularly in relation to the construction and expression of social preferences.


Analyzing sociodemographic factors amongst blood donors.
Blood transfusion is a fundamental and requisite part of any National Health Service for optimum management of emergency conditions like severe trauma shock and resuscitation with the optimum stock of its different components. The objective of the present study was to analyze the factors of knowledge of prospective blood donors that may influence their perception and awareness about blood donation. This population-based cross-sectional study was conducted at Gangtok in the state of Sikkim, India, on 300 subjects of the adult population selected by two-stage cluster sampling. The main outcome variables were the socioeconomic and demographic variables of knowledge of blood donation. By interview technique, using the pre-tested structured close-ended questionnaire, the principal investigator collected the data. In our study population, 46% of the study population was found to have a high knowledge score. The knowledge about blood donation was found to be statistically significant with the occupational status and the education levels, both in the bivariate and in the multivariate analyses. Knowledge about blood donation was not significantly related to age, sex, marital status, religion, community status and per capita monthly family income. The study suggested that the perceptions toward voluntary blood donation could be influenced to a large extent by sociodemographic variables of knowledge among the general population.


Evolutionary dynamics of recently duplicated genes: Selective constraints on diverging paralogs in the Drosophila pseudoobscura genome.
Duplicated genes produce genetic variation that can influence the evolution of genomes and phenotypes. In most cases, for a duplicated gene to contribute to evolutionary novelty it must survive the early stages of divergence from its paralog without becoming a pseudogene. I examined the evolutionary dynamics of recently duplicated genes in the Drosophila pseudoobscura genome to understand the factors affecting these early stages of evolution. Paralogs located in closer proximity have higher sequence identity. This suggests that gene conversion occurs more often between duplications in close proximity or that there is more genetic independence between distant paralogs. Partially duplicated genes have a higher likelihood of pseudogenization than completely duplicated genes, but no single factor significantly contributes to the selective constraints on a completely duplicated gene. However, DNA-based duplications and duplications within chromosome arms tend to produce longer duplication tracts than retroposed and inter-arm duplications, and longer duplication tracts are more likely to contain a completely duplicated gene. Therefore, the relative position of paralogs and the mechanism of duplication indirectly affect whether a duplicated gene is retained or pseudogenized.


Does medication administration affect the rate of orthodontic tooth movement and root resorption development in humans? A systematic review.
Recently, the potential impact of different medications on the rate of orthodontic tooth movement and the associated root resorption has been systematically reviewed in animal studies and various effects have been shown. However, animal data cannot be extrapolated to human clinical situations directly. To systematically investigate the most up to date available evidence from controlled human studies regarding the effect of medication administration on the rate of orthodontic tooth movement and associated root resorption development. We searched eight databases (covering also grey literature) without restrictions and we performed hand searching up until October 2018. Controlled studies in humans assessing the effect of various medications on the rate of orthodontic tooth movement and root resorption development. Study selection was followed by data extraction and risk of bias assessment using the ROBINS-I tool for non-randomized and the Cochrane Risk of Bias Tool for randomized studies. Eight studies, at various risk of bias, were finally identified. With regard to the rate of orthodontic tooth movement, local injections of prostaglandin E1 were found to exert an increasing effect, whereas systemic intake of nabumetone decreased it. Following tenoxicam administration, drinking water with fluoride or local injections of calcitriol (vitamin D metabolite), no significant effects were demonstrated. Concerning root resorption development, nabumetone administration was shown to reduce it, whereas fluoride, overall, was not observed to exert any effect. Only in individuals subjected to heavy orthodontic forces, did fluoride show a protective effect for the period of force application, but not in the longer term during retention. The aforementioned substances may show varying effects on the rate of orthodontic tooth movement and root resorption development in human subjects. Despite the observed limitations, the orthodontist should be able to identify patients taking pharmaceuticals and consider any implications related to orthodontic treatment. PROSPERO (CRD42017078208).


[Diagnostics of lung contusion in patients with thoracic closed injury and prophylaxis of complications].
Among 304 patients hospitalised with thorax closed injury 205 patients had lung contusion. The use of a complex diagnostics allowed to discharge 176 patients without any complications. The development of complections was observed in 128 patients, which occurred after the patients had had their injuries. Application of endoscopic sanation and treatment allowed to discharge patients in early terms.


Serological investigations into the presence of antibodies to Yaba 1--Lednice 110 virus in Romania.
Sera collected from several migratory birds of the Danube Delta, from humans and domestic birds and animals of three Romanian counties were tested by hemagglutination-inhibition reaction for the presence of antibodies to Yaba 1--Lednice 110 virus. Antibodies could be detected in only 8 of the 14 species of migratory birds included in the study, especially in wild geese and ducks.


Nasal packing after septoplasty: cardiopulmonary impact.
Bilateral anterior nasal packing is used after septoplasty with the goals of decreasing the risk of postoperative bleeding and adhesions. However, multiple studies caution against the use of nasal packing because of the risk of cardiopulmonary complications. To evaluate the cardiopulmonary risks associated with bilateral anterior nasal packing after septoplasty. A literature review was conducted by 2 independent reviewers using EMBASE, Ovid, Medline, PubMed, Google Scholar, Cochrane Central Register of Controlled Trials (CENTRAL), and reference list review from January 1966 to September 2012 to identify studies assessing nasal packing after septoplasty. The studies were reviewed and assigned an Oxford level of evidence grade, Detsky score, and Methodological Index for Nonrandomized Studies (MINORS) score. Data were extracted for arterial blood gases, oxygen desaturations, oxygen saturations, and adverse outcomes. Pooled estimates for randomized studies were performed when possible. Fourteen studies conducted between 1973 and 2011 were included: 2 randomized clinical trials (RCTs) with a total of 119 patients and 12 prospective observational studies with a total of 356 patients. Nine studies showed a significant change within 1 of the cardiopulmonary parameters investigated. However, there was no consistency in changes across both observational and randomized studies. Furthermore, pooled estimates for cardiopulmonary parameters were all nonsignificant: standard mean differences of the pooled results of the RCTs were 0.05 (95% CI, -0.31 to 0.41) for arterial pH, 0.08 (95% CI, -0.30 to 0.46) for Paco2, and -0.32 (95% CI, -1.28 to 0.63) for Pao2. There were no major cardiopulmonary complications after nasal packing. Bilateral anterior nasal packing does not seem to cause adverse cardiopulmonary changes after septoplasty.


Occurrence of microbial indicators and Clostridium perfringens in wastewater, water column samples, sediments, drinking water, and Weddell seal feces collected at McMurdo Station, Antarctica.
McMurdo Station, Antarctica, has discharged untreated sewage into McMurdo Sound for decades. Previous studies delineated the impacted area, which included the drinking water intake, by using total coliform and Clostridium perfringens concentrations. The estimation of risk to humans in contact with the impacted and potable waters may be greater than presumed, as these microbial indicators may not be the most appropriate for this environment. To address these concerns, concentrations of these and additional indicators (fecal coliforms, Escherichia coli, enterococci, coliphage, and enteroviruses) in the untreated wastewater, water column, and sediments of the impacted area and drinking water treatment facility and distribution system at McMurdo Station were determined. Fecal samples from Weddell seals in this area were also collected and analyzed for indicators. All drinking water samples were negative for indicators except for a single total coliform-positive sample. Total coliforms were present in water column samples at higher concentrations than other indicators. Fecal coliform and enterococcus concentrations were similar to each other and greater than those of other indicators in sediment samples closer to the discharge site. C. perfringens concentrations were higher in sediments at greater distances from the discharge site. Seal fecal samples contained concentrations of fecal coliforms, E. coli, enterococci, and C. perfringens similar to those found in untreated sewage. All samples were negative for enteroviruses. A wastewater treatment facility at McMurdo Station has started operation, and these data provide a baseline data set for monitoring the recovery of the impacted area. The contribution of seal feces to indicator concentrations in this area should be considered.


Preconcentration of volatile organics on self-assembled, carbon nanotubes in a microtrap.
This paper reports the self-assembly of carbon nanotubes (CNTs) on the inside wall of a steel capillary to fabricate a microtrap for the adsorption/desorption of trace organics. The microtrap functioned as a nanoconcentrator and an injector for gas chromatography (GC). The CNTs were deposited as a thin film by catalytic chemical vapor deposition from either CO or C2H4 as the precursor. The sorbent film synthesized from C2H4-CVD (CVD = chemical vapor deposition) had higher CNT density and thus was a stronger sorbent. In general, the CNT microtraps showed high-capacity adsorption and fast quantitative desorption, and the process showed excellent precision. This study demonstrates that CNT films can be deposited quite easily in a steel capillary for use in different analytical applications, and CNT films can perform as efficiently as packed-bed carbon sorbents.


Clinical impact of different exosomes' protein expression in pancreatic ductal carcinoma patients treated with standard first line palliative chemotherapy.
Pancreatic ductal adenocarcinoma is associated to dismal prognosis despite the use of palliative chemotherapy, partly due to the lack of knowledge of biological processes underlying disease progression. Exosomes have been identified as biomarkers sources in different cancer types. Aim of the study was to analyse the contents of circulating exosomes in patients with pancreatic cancer who received palliative chemotherapy. Patients were submitted to blood sample collection before chemotherapy (T0) and after 3 months (T3). We quantified by an ELISA-based technique specific proteins of cancer-derived exosomes (CD44,CD44v6,EpCAM,CD9,CD81,Tspan8,Integrin α6,Integrin β4,CD24,CXCR4). We correlated the baseline levels of these factors and changes between T3 and T0 and survival outcomes. Survival analyses were performed by Kaplan-Meier method. Correlation was assessed by log-rank test and level of statistical significance was set at 0.05. Multivariate analysis was performed by logistic regression analysis. Nineteen patients were enrolled. EpCAM T0 levels and increased EpCAM levels from T0 to T3 were those mostly associated with differences in survival. Patients having higher EpCAM had median progression free survival (PFS) of 3.18vs7.31 months (HR:2.82,95%CI:1.03-7.73,p = 0.01). Overall survival (OS) was shorter for patients having higher EpCAM (5.83vs16.45 months,HR:6.16,95%CI:1.93-19.58,p = 0.0001) and also response rates (RR) were worse (20%vs87%,p = 0.015). EpCAM increase during treatment was associated with better median PFS (2.88vs7.31 months,HR:0.24,95%CI:0.04-1.22,p = 0.003). OS was also better (8.75vs11.04 months, HR:0.77,95%CI:0.21-2.73,p = 0.66) and RR were 60%vs20% (p = 0.28). Among clinical factors that might determine changes on PFS and OS, only ECOG PS was associated to significantly worse PFS and OS (p = 0.0137and<0.001 respectively).Multivariate analysis confirmed EpCAM T0 levels and EpCAM T0/T3 changes as independent prognostic factors for PFS. Pancreatic cancer patients exosomes express EpCAM, whose levels change during treatment. This represents a useful prognostic factor and also suggests that future treatment modalities who target EpCAM should be tested in pancreatic cancer patients selected by exosome EpCAM expression.


Harm Reduction in Male Patients Actively Using Anabolic Androgenic Steroids (AAS) and Performance-Enhancing Drugs (PEDs): a Review.
Anabolic androgenic steroid (AAS) and performance-enhancing drug (PED) use is a prevalent medical issue, especially among men, with an estimated 2.9-4 million Americans using AAS in their lifetime. Prior studies of AAS use reveal an association with polycythemia, dyslipidemia, infertility, hypertension, left ventricular hypertrophy, and multiple behavioral disorders. AAS withdrawal syndrome, a state of depression, anhedonia, and sexual dysfunction after discontinuing AAS use, is a common barrier to successful cessation. Clinical resources for these patients and training of physicians on management of the patient using AAS are limited. Many men are hesitant to seek traditional medical care due to fear of judgment and lack of confidence in physician knowledge base regarding AAS. While proposed approaches to weaning patients off AAS are published, guidance on harm reduction for actively using patients remains sparse. Medical education regarding the management of AAS use disorder is paramount to improving care of this currently underserved patient population. Management of these patients must be non-judgmental and focus on patient education, harm reduction, and support for cessation. The approach to harm reduction should be guided by the specific AAS/PEDs used.


Inhibition of the ANT(2")-Ia resistance enzyme and rescue of aminoglycoside antibiotic activity by synthetic α-hydroxytropolones.
Aminoglycoside-2"-O-nucleotidyltransferase ANT(2")-Ia is an aminoglycoside resistance enzyme prevalent among Gram-negative bacteria, and is one of the most common determinants of enzyme-dependant aminoglycoside-resistance. The following report outlines the use of our recently described oxidopyrylium cycloaddition/ring-opening strategy in the synthesis and profiling of a library of synthetic α-hydroxytropolones against ANT(2")-Ia. In addition, we show that two of these synthetic constructs are capable of rescuing gentamicin activity against ANT-(2")-Ia-expressing bacteria.


The Beneficial Effect of Probiotics Supplementation on Penicillin-Induced Focal Seizure in Rats.
The focal epilepsy is a chronic neurological brain disorder which affects millions of people in the world. There is emerging evidence that changes in the gut microbiota may have effects on epileptic seizures. In the present study, we examined the effect of probiotics on penicillin-induced focal seizure model in rats. Male Wistar Albino rats (n: 21) were randomly divided into three groups: control (no medication), penicillin and penicillin + probiotic. Probiotic VSL#3 (12.86 bn living bacteria/kg/day) was given by gavage for 30 days. The seizures were induced by intracortical injection of penicillin G (500 IU) into the cortex. An ECoG recordings were made for 180 min after penicillin G application. The spike frequency and the amplitude were used to assess the severity of seizures. Tumor necrosis factor (TNF-α), nitric oxide (NO) and interleukin (IL-6) levels in the brain were studied biochemically. Our results indicated that probiotic supplementation improved focal seizures through increasing the latency (p < 0.001) and decreasing the spike frequency (p < 0.01) compared to the penicillin group. Penicillin-induced seizure in rats significantly enhanced TNF-α (p < 0.01), NO (p < 0.01) and IL-6 (p < 0.05) compared to the control. Probiotic supplementation significantly decreased IL-6 (p < 0.05), TNF-α (p < 0.01) and NO (p < 0.001) compared to the penicillin group. When the body weights were compared before and after the experiment, there was no difference between the control and penicillin groups, but it was observed that the body weight decreased after probiotic supplementation in the penicillin + probiotic group. Probiotic supplementation may have anti-seizure effect by reducing proinflammatory cytokine and NO levels in epileptic rat brain.


Postnatal regulation of canine oxygen delivery: erythrocyte components affecting Hb function.
A rightward shift in the blood oxygen dissociation curve occurs during the 1st mo of canine life. A detailed peptide analysis indicated that dogs do not have a separate fetal hemoglobin. Other erythrocyte components such as ATP, K+, Na+, and H+ were excluded as significant mediators of the postnatal oxygen affinity change. Erythrocyte 2,3-DPG levels essentially zero in fetal dogs, increased rapidly during the 1st mo of canine life. There was a significant correlation between this postnatal 2,3-DPG increase and the postnatal decrease in blood oxygen affinity. Dialyzed hemolysates of fetal or adult canine blood have the same intrinsic oxygen affinity and the same response to normal adult levels of 2,3-DPG. Furthermore, the magnitude and direction of this 2,3-DPG-induced decrease in oxygen affinity in vitro are comparable to the in vivo postnatal change in oxygen affinity.


Toxoplasma gondii Oocyst Infectivity Assessed Using a Sporocyst-Based Cell Culture Assay Combined with Quantitative PCR for Environmental Applications.
Toxoplasma gondii is a ubiquitous foodborne protozoan that can infect humans at low dose and displays different prevalences among countries in the world. Ingestion of food or water contaminated with small amounts of T. gondii oocysts may result in human infection. However, there are no regulations for monitoring oocysts in food, mainly because of a lack of standardized methods to detect them. The objectives of this study were (i) to develop a reliable method, applicable in biomonitoring, for the rapid detection of infectious oocysts by cell culture of their sporocysts combined with quantitative PCR (sporocyst-CC-qPCR) and (ii) to adapt this method to blue and zebra mussels experimentally contaminated by oocysts with the objective to use these organisms as sentinels of aquatic environments. Combining mechanical treatment and bead beating leads to the release of 84% ± 14% of free sporocysts. The sporocyst-CC-qPCR detected fewer than ten infectious oocysts in water within 4 days (1 day of contact and 3 days of cell culture) compared to detection after 4 weeks by mouse bioassay. For both mussel matrices, oocysts were prepurified using a 30% Percoll gradient and treated with sodium hypochlorite before cell culture of their sporocysts. This assay was able to detect as few as ten infective oocysts. This sporocyst-based CC-qPCR appears to be a good alternative to mouse bioassay for monitoring infectious T. gondii oocysts directly in water and also using biological sentinel mussel species. This method offers a new perspective to assess the environmental risk for human health associated with this parasite.IMPORTANCE The ubiquitous protozoan Toxoplasma gondii is the subject of renewed interest due to the spread of oocysts in water and food causing endemic and epidemic outbreaks of toxoplasmosis in humans and animals worldwide. Displaying a sensitivity close to animal models, cell culture represents a real alternative to assess the infectivity of oocysts in water and in biological sentinel mussels. This method opens interesting perspectives for evaluating human exposure to infectious T. gondii oocysts in the environment, where oocyst amounts are considered to be very small.


In vitro synthesis of triphosphate-initiated N-gene mRNA oligonucleotides is regulated by the matrix protein of vesicular stomatitis virus.
Wild-type Indiana virus transcribed four 11- to 14-nucleotide-long, 5' N-gene mRNA sequences in vitro. The amount of oligonucleotides synthesized relative to leader by wild-type virions varied inversely with the salt concentration of the transcription reaction. Reduced oligonucleotide synthesis by nucleocapsids at all salt concentrations tested and a comparison of the proteins remaining bound to the template of nucleocapsids and virions transcribed in different NaCl concentrations suggested that the matrix (M) protein regulates oligonucleotide synthesis. Examination of the transcription products synthesized in no NaCl and 0.144 M NaCl by an M-protein mutant and an increase in oligonucleotide synthesis by nucleocapsids when purified M-protein was added to transcription reactions confirmed M-protein's role in oligonucleotide synthesis. Wild-type virion mRNA synthesis was inhibited, and oligonucleotide synthesis was greater than leader synthesis at high virus concentrations. As the virus was diluted, inhibition of mRNA synthesis was relieved and oligonucleotide synthesis was reduced. The M-protein mutant tsG33 exhibited neither transcription inhibition at high virus concentrations nor the reciprocal synthesis of mRNA and the oligonucleotides seen with wild-type virions. These results are entirely consistent with the stop-start model of transcription and suggest a model for the control of transcription by M-protein.


Extracorporeal Life Support in Infarct-Related Cardiogenic Shock.
Extracorporeal life support (ECLS) is increasingly used in the treatment of infarct-related cardiogenic shock despite a lack of evidence regarding its effect on mortality. In this multicenter trial, patients with acute myocardial infarction complicated by cardiogenic shock for whom early revascularization was planned were randomly assigned to receive early ECLS plus usual medical treatment (ECLS group) or usual medical treatment alone (control group). The primary outcome was death from any cause at 30 days. Safety outcomes included bleeding, stroke, and peripheral vascular complications warranting interventional or surgical therapy. A total of 420 patients underwent randomization, and 417 patients were included in final analyses. At 30 days, death from any cause had occurred in 100 of 209 patients (47.8%) in the ECLS group and in 102 of 208 patients (49.0%) in the control group (relative risk, 0.98; 95% confidence interval [CI], 0.80 to 1.19; P = 0.81). The median duration of mechanical ventilation was 7 days (interquartile range, 4 to 12) in the ECLS group and 5 days (interquartile range, 3 to 9) in the control group (median difference, 1 day; 95% CI, 0 to 2). The safety outcome consisting of moderate or severe bleeding occurred in 23.4% of the patients in the ECLS group and in 9.6% of those in the control group (relative risk, 2.44; 95% CI, 1.50 to 3.95); peripheral vascular complications warranting intervention occurred in 11.0% and 3.8%, respectively (relative risk, 2.86; 95% CI, 1.31 to 6.25). In patients with acute myocardial infarction complicated by cardiogenic shock with planned early revascularization, the risk of death from any cause at the 30-day follow-up was not lower among the patients who received ECLS therapy than among those who received medical therapy alone. (Funded by the Else Kröner Fresenius Foundation and others; ECLS-SHOCK ClinicalTrials.gov number, NCT03637205.).


Heterophoria as a measure of subjects' alertness during recovery from general anesthesia.
The purpose of the study was to measure the influence of subjects' alertness on heterophoria. An experimental group of 43 patients was measured with the Maddox Wing test for heterophoria. Exophoria was greater 1 1/2, 2 1/2, and 3 1/2 hr. after the end of general anesthesia than at baseline level. Data for a control group of 25 did not vary on the Maddox Wing over four hours. The baseline level was not different between the two groups, so heterophoria as measured with the Maddox Wing can be used to evaluate subjects' alertness during recovery from general anesthesia.


On the Elusive Links between Solution Microstructure, Dynamics, and Solvation Thermodynamics: Demystifying the Path through a Bridge over Troubled Conjectures and Misinterpretations.
We build a fundamentally based bridge between the solute-induced microstructural perturbation of the species environment and the dynamic as well as thermodynamic responses of the fluid system, regardless of the state conditions, composition, nature of the solvent, and either the magnitude or the type of solute-solvent intermolecular-interaction asymmetries. For that purpose, we advance a fluctuation-based solvation formalism of fluid mixtures to provide meaningful descriptors of solvation phenomena, the microstructural signatures of their solute-solvent intermolecular interaction asymmetry, and the thermodynamic manifestations linked to the solution nonideality. The rigorous foundations afford us to address some crucial issues frequently invoked in the literature including the microstructural perturbation domain, its proper identification and molecular-based meaning toward the interpretation of the solvation process, and the potential impact of the local differential behavior between anions and cations on the actual salt-induced perturbation of the solvent microstructure. Indeed, we link the precisely characterized species solvation behavior to fundamental thermodynamic residual-property relations, and the dynamics associated with either the viscous flow or diffusive behavior of the solvent, to finally illustrate their outcome with experimental data of aqueous electrolyte solutions from the available literature. Ultimately, this effort provides a highly desirable unambiguous identification of the cause-effect connections between the microstructurally perturbed domains and the experimentally measured macroscopic solvation properties, including their effect on the dynamics of the solvent environment. More importantly, it lends a well-established solvation framework to bridge rigorously the microstructural details of the mixture, its dynamics, and its solvation thermodynamics to enhance our understanding of well-defined ranked Hofmeister series, i.e., by avoiding ad hoc conjectures and unsupported microscopic interpretations of solvation phenomena.


Monitoring and ordering practices for human papillomavirus in cervical cytology: findings from the College of American Pathologists Gynecologic Cytopathology Quality Consensus Conference working group 5.
The association of certain types of human papillomavirus with cervical carcinoma is well established. Human papillomavirus testing is now routinely used to screen for cervical carcinoma and precursor lesions of the cervix (cotesting and reflex testing) and these results are considered in patient triage and management. To provide information about current laboratory practices in human papillomavirus testing and consensus best practice statements based on results from the College of American Pathologists' laboratory-based survey funded by the Centers for Disease Control and Prevention. The College of American Pathologists submitted a paper-based survey to 1245 laboratories in the United States. After review of the initial results, follow-up Web-based survey results, and a literature review by an expert working group, consensus best practice statements were constructed by working group members for presentation at a national consensus conference. These best practice statements were discussed and then voted upon by conference participants. A total of 525 laboratories responded to survey questions about human papillomavirus ordering and monitoring practices, whereas 546 responded to the overall survey. In most laboratories (87.6%), the high-risk human papillomavirus test is ordered as a reflex test by providers. A minority of laboratories (11.9%) routinely bundle low- and high-risk human papillomavirus tests. Most laboratories (84.4%) do not limit testing in patients with atypical squamous cells to women older than 20 years. More than half of laboratories (53.3%) monitor human papillomavirus positive rates in Papanicolaou tests with atypical squamous cells of undetermined significance. It is not appropriate for laboratories to offer low-risk human papillomavirus testing for any clinical circumstance in gynecologic cytology. Laboratories should not order human papillomavirus testing to resolve diagnostic discrepancies. It is a valuable broad measure of laboratory quality to monitor the human papillomavirus-positive rates in Papanicolaou tests with atypical squamous cells.


Intracellular activation of interferon regulatory factor-1 by nanobodies to the multifunctional (Mf1) domain.
IRF-1 is a tumor suppressor protein that activates gene expression from a range of promoters in response to stimuli spanning viral infection to DNA damage. Studies on the post-translational regulation of IRF-1 have been hampered by a lack of suitable biochemical tools capable of targeting the endogenous protein. In this study, phage display technology was used to develop a monoclonal nanobody targeting the C-terminal Mf1 domain (residues 301-325) of IRF-1. Intracellular expression of the nanobody demonstrated that the transcriptional activity of IRF-1 is constrained by the Mf1 domain as nanobody binding gave an increase in expression from IRF-1-responsive promoters of up to 8-fold. Furthermore, Mf1-directed nanobodies have revealed an unexpected function for this domain in limiting the rate at which the IRF-1 protein is degraded. Thus, the increase in IRF-1 transcriptional activity observed on nanobody binding is accompanied by a significant reduction in the half-life of the protein. In support of the data obtained using nanobodies, a single point mutation (P325A) involving the C-terminal residue of IRF-1 has been identified, which results in greater transcriptional activity and a significant increase in the rate of degradation. The results presented here support a role for the Mf1 domain in limiting both IRF-1-dependent transcription and the rate of IRF-1 turnover. In addition, the data highlight a route for activation of downstream genes in the IRF-1 tumor suppressor pathway using biologics.


Quantitative intramuscular myoelectric activity of lumbar portions of psoas and the abdominal wall during a wide variety of tasks.
Since most previous reports of EMG activation profiles from psoas and the abdominal wall have been qualitative, the objective of this work was to document myoelectric activity from these deep muscles. This knowledge is required to assist in choosing specific training exercises and for making rehabilitation decisions that require knowledge of normalized and calibrated muscle activation levels in different tasks. Intramuscular EMG was collected from five men and three women, in whom amplitudes were normalized to maximum contraction efforts and reported over a wide variety of clinical and rehabilitation tasks. Electrodes were inserted into vertebral portions of psoas and the three layers of the abdominal wall. Normalized signal amplitudes were reported as peak levels and time histories. All forms of sit-ups activated psoas (15-35% MVC) more than the curl-up (<10%); psoas was not highly activated during barbell lifting of loads up to 100 kg (< 16% MVC); psoas was most active during maximal hip flexion efforts; push-ups activated psoas up to 25% MVC. Several isometric abdominal exercises were evaluated using the criteria of maximizing abdominal activation while minimizing psoas activity: the side (bridge) support exercise proved the best training method for the abdominal wall. Consideration of deep muscle activity, provided in this report, is important for choosing the most appropriate rehabilitation and training program for an individual. Specific guidance is provided for choosing the best abdominal exercise, together with activation profiles during lifting, during twisting, and during hip rotation.


The role of alpha 4 integrin and intercellular adhesion molecule-1 (ICAM-1) in murine experimental autoimmune thyroiditis.
Mouse-thyroglobulin (MTg)-sensitized spleen cells activated in vitro with MTg induce a lymphocytic form of experimental autoimmune thyroiditis (EAT) whereas activation of the same cell population with MTg in the presence of anti-interleukin 2 receptor antibody (M7/20) induces a granulomatous form of EAT. The thyroid infiltrate in both lymphocytic and granulomatous EAT includes both CD4+ and CD8+ T cells and CD4+ T cells are the primary effector cells for both forms of EAT. This investigation was undertaken to begin to define the roles of alpha 4 integrin, and intercellular adhesion molecule-1 (ICAM-1) in the migration of CD4+ and CD8+ T cells to the thyroid in EAT. The studies presented here demonstrate the expression of alpha 4 integrin and ICAM-1 on CD4+ and CD8+ T cells infiltrating the thyroid and the expression of vascular cell adhesion molecule (VCAM) and ICAM-1 on thyroid cells of mice with EAT. The effects of anti-alpha 4 and anti-ICAM mAb administration on EAT severity in recipient mice was also determined. Anti-alpha 4 administration reduced or abolished lymphocyte infiltration in the thyroid resulting in reduced severity of both lymphocytic and granulomatous EAT. In contrast, anti-ICAM mAb had little effect on EAT severity. These results suggest that these two adhesion molecules exhibit differential functional roles in the modulation of EAT disease severity and that alpha 4-VCAM interactions may be of particular importance in trafficking of effector cells to the thyroid.


The alternatively spliced domains EIIIB and EIIIA of human fibronectin affect cell adhesion and spreading.
Fibronectin has a complex pattern of alternative splicing at the pre-mRNA level leading to the expression of different isoforms. The alternatively spliced domains EIIIB and EIIIA are known to be prominently expressed during development and wound healing. While the other spliced domain (CS-segment) is known to promote cell adhesion in a cell type specific manner, the biological functions of the spliced domains EIIIB and EIIIA are not well understood. In the present study, we have prepared expression proteins of specific domains of human fibronectin using a prokaryotic expression system and used the purified fragments to test their ability to support adhesion and spreading of cultured cells. Fragments from type-III domains #7 to #12 were prepared in various combinations to include or exclude the spliced domains EIIIB and EIIIA. The results indicate that cultured NIL fibroblasts adhere to many of the fragments tested. However, the cell adhesion and spreading are enhanced, especially at lower concentrations, to fragments including the domain EIIIB. The inclusion of domain EIIIA led to a decrease in the adhesion of cells and those that adhered did not spread well. When tested in a centrifugal cell adhesion assay, fragments including domain EIIIB resisted the detaching forces and stayed adhered. Fragments that included domain EIIIA were unable to resist the detaching centrifugal forces to the same extent as the fragments that included domain EIIIB alone. These results suggest that the spliced domain EIIIB may be serving important biological functions in enhancing cell adhesion and spreading. This is likely to be mediated by conformational effects because domain EIIIB alone neither exhibited any adhesive activity nor competed in inhibiting adhesion to fragments #7-10.


Cortisol, DHEA sulphate, their ratio, and all-cause and cause-specific mortality in the Vietnam Experience Study.
The aim of the present analyses was to examine the association between cortisol, DHEA sulphate (DHEAS) and the cortisol:DHEAS ratio and mortality. This was a prospective cohort analysis. Participants were 4255 Vietnam-era US army veterans. From military service files, telephone interviews and a medical examination, occupational, socio-demographic and health data were collected. Contemporary morning fasted cortisol and DHEAS concentrations were determined. Mortality was tracked over the subsequent 15 years. The outcomes were all-cause, cardiovascular disease, cancer, other medical mortality and external causes of death. Cox proportional hazard models were tested, initially with adjustment for age, and then with adjustment for a range of candidate confounders. In general, cortisol concentrations did not show an association with all-cause or cause-specific mortality. However, in age-adjusted and fully adjusted analyses, DHEAS was negatively related to all-cause, all cancers and other medical mortality; high DHEAS concentrations were protective. The cortisol:DHEAS ratio was also associated with these outcomes in both age-adjusted and fully adjusted models; the higher the ratio, the greater the risk of death. DHEAS was negatively associated, and the ratio of cortisol to DHEAS was positively associated with all-cause, cancer and other medical cause mortality. Further experimental study is needed to elucidate the mechanisms involved in these relationships.


Pathological muscle activation patterns in patients with massive rotator cuff tears, with and without subacromial anaesthetics.
A mechanical deficit due to a massive rotator cuff tear is generally concurrent to a pain-induced decrease of maximum arm elevation and peak elevation torque. The purpose of this study was to measure shoulder muscle coordination in patients with massive cuff tears, including the effect of subacromial pain suppression. Ten patients, with MRI-proven cuff tears, performed an isometric force task in which they were asked to exert a force in 24 equidistant intervals in a plane perpendicular to the humerus. By means of bi-polar surface electromyography (EMG) the direction of the maximal muscle activation or principal action of six muscles, as well as the external force, were identified prior to, and after subacromial pain suppression. Subacromial lidocaine injection led to a significant reduction of pain and a significant increase in exerted arm force. Prior to the pain suppression, we observed an activation pattern of the arm adductors (pectoralis major pars clavicularis and/or latissimus dorsi and/or teres major) during abduction force delivery in eight patients. In these eight patients, adductor activation was different from the normal adductor activation pattern. Five out of these eight restored this aberrant activity (partly) in one or more adductor muscles after subacromial lidocaine injection. Absence of glenoid directed forces of the supraspinate muscle and compensation for the lost supraspinate abduction torque by the deltoideus leads to destabilizating forces in the glenohumeral joint, with subsequent upward translation of the humeral head and pain. In order to reduce the superior translation force, arm adductors will be co-activated at the cost of arm force and abduction torque. Pain seems to be the key factor in this (avoidance) mechanism, explaining the observed limitations in arm force and limitations in maximum arm elevation in patients suffering subacromial pathologies. Masking this pain may further deteriorate the subacromial tissues as a result of proximal migration of the humeral head and subsequent impingement of subacromial tissues.


Klebsiella pneumoniae Carbapenemase-2 (KPC-2), Substitutions at Ambler Position Asp179, and Resistance to Ceftazidime-Avibactam: Unique Antibiotic-Resistant Phenotypes Emerge from β-Lactamase Protein Engineering.
The emergence of Klebsiella pneumoniae carbapenemases (KPCs), β-lactamases that inactivate "last-line" antibiotics such as imipenem, represents a major challenge to contemporary antibiotic therapies. The combination of ceftazidime (CAZ) and avibactam (AVI), a potent β-lactamase inhibitor, represents an attempt to overcome this formidable threat and to restore the efficacy of the antibiotic against Gram-negative bacteria bearing KPCs. CAZ-AVI-resistant clinical strains expressing KPC variants with substitutions in the Ω-loop are emerging. We engineered 19 KPC-2 variants bearing targeted mutations at amino acid residue Ambler position 179 in Escherichia coli and identified a unique antibiotic resistance phenotype. We focus particularly on the CAZ-AVI resistance of the clinically relevant Asp179Asn variant. Although this variant demonstrated less hydrolytic activity, we demonstrated that there was a prolonged period during which an acyl-enzyme intermediate was present. Using mass spectrometry and transient kinetic analysis, we demonstrated that Asp179Asn "traps" β-lactams, preferentially binding β-lactams longer than AVI owing to a decreased rate of deacylation. Molecular dynamics simulations predict that (i) the Asp179Asn variant confers more flexibility to the Ω-loop and expands the active site significantly; (ii) the catalytic nucleophile, S70, is shifted more than 1.5 Å and rotated more than 90°, altering the hydrogen bond networks; and (iii) E166 is displaced by 2 Å when complexed with ceftazidime. These analyses explain the increased hydrolytic profile of KPC-2 and suggest that the Asp179Asn substitution results in an alternative complex mechanism leading to CAZ-AVI resistance. The future design of novel β-lactams and β-lactamase inhibitors must consider the mechanistic basis of resistance of this and other threatening carbapenemases.IMPORTANCE Antibiotic resistance is emerging at unprecedented rates and threatens to reach crisis levels. One key mechanism of resistance is the breakdown of β-lactam antibiotics by β-lactamase enzymes. KPC-2 is a β-lactamase that inactivates carbapenems and β-lactamase inhibitors (e.g., clavulanate) and is prevalent around the world, including in the United States. Resistance to the new antibiotic ceftazidime-avibactam, which was designed to overcome KPC resistance, had already emerged within a year. Using protein engineering, we uncovered a mechanism by which resistance to this new drug emerges, which could arm scientists with the ability to forestall such resistance to future drugs.


Amphibacillus sediminis sp. nov., an endospore-forming bacterium isolated from lake sediment in Japan.
A facultatively anaerobic, moderately alkaliphilic, Gram-positive, spore-forming and rod-shaped bacterial strain, Shu-P-Ggiii25-2T, was isolated from lake sediment in Shizuoka, Japan, and was characterized taxonomically using a polyphasic approach. Analysis of the 16S rRNA gene sequence indicated that the novel isolate clustered with the type strain of Amphibacillus xylanus and it exhibited sequence similarities of 94.9-95.6% to the type strains of species of the genus Amphibacillus. Isoprenoid quinones and oxidase and catalase activities were not detected for strain Shu-P-Ggiii25-2T. The DNA G+C content was 42.3 mol%, the cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid and the major cellular fatty acids were iso-C14:0, iso-C15:0, anteiso-C15:0, C16:0 and iso-C16:0. On the basis of phylogenetic position and phenotypic properties, strain Shu-P-Ggiii25-2T represents a novel species of the genus Amphibacillus, for which the name Amphibacillus sediminis sp. nov. is proposed. The type strain is Shu-P-Ggiii25-2T (=MBIC08269T=IAM 15428T=KCTC 13120T). An emended description of the genus Amphibacillus is also given.


The Acute Physiology and Chronic Health Evaluation II score is helpful in predicting the need of relaparotomies in patients with secondary peritonitis of colorectal origin.
Secondary peritonitis of colorectal origin has considerable morbidity and mortality. Relaparotomies are frequently necessary in the course of the disease. The objective of this study was to evaluate several scores in terms of their predictive value, i.e. whether Mannheim Peritonitis Index (MPI), Acute Physiology And Chronic Health Evaluation (APACHE) II, or Colorectal Physiological and Operative Severity Score for the Enumeration of Mortality and Morbidity (CR-POSSUM) scores can predict relaparotomies. Charts of 147 patients treated for secondary peritonitis of colorectal origin were retrospectively reviewed, MPI, APACHE II, and CR-POSSUM scores were calculated, and groups of patients with or without relaparotomies were compared. Thirty-four percent of patients underwent one or more relaparotomies. Patients with relaparotomies showed a significantly higher APACHE II score than patients without relaparotomies (p = 0.004). MPI (p = 0.072) and CR-POSSUM score (p = 0.319) did not differ between the two groups. A high APACHE II score was also significantly associated with the need for a relaparotomy on demand (p <0.001), and for the combined outcome parameter relaparotomy and/or an interventional drainage (p = 0.046). Both other scores were not predictive for these outcomes. Overall in-hospital mortality was 21.8%. All three scores investigated were predictive for mortality. Sensitivity was 62.5%, 78.1%, and 75.0% for MPI, APACHE II score, and CR-POSSUM score, respectively. The Acute Physiology And Chronic Health Evaluation II score might be helpful in predicting the need for relaparotomies in patients with secondary peritonitis of colorectal origin.


Portal Vein Pulsatility as a Dynamic Marker of Venous Congestion Following Cardiac Surgery: An Interventional Study Using Positive End-Expiratory Pressure.
We aimed to assess variations in the portal vein pulsatility index (PI) during mechanical ventilation following cardiac surgery. After ethical approval, we conducted a prospective monocentric study at Amiens University Hospital. Patients under mechanical ventilation following cardiac surgery were enrolled. Doppler evaluation of the portal vein (PV) was performed by transthoracic echography. The maximum velocity (VMAX) and minimum velocity (VMIN) of the PV were measured in pulsed Doppler mode. The PI was calculated using the following formula (VMAX - VMIN)/(VMax). A positive end-expiratory pressure (PEEP) incremental trial was performed from 0 to 15 cmH2O, with increments of 5 cmH2O. The PI (%) was assessed at baseline and PEEP 5, 10, and 15 cmH2O. Echocardiographic and hemodynamic parameters were recorded. In total, 144 patients were screened from February 2018 to March 2019 and 29 were enrolled. Central venous pressure significantly increased for each PEEP increment. Stroke volumes were significantly lower after PEEP incrementation, with 52 mL (50-55) at PEEP 0 cmH2O and 30 mL (25-45) at PEEP 15 cmH2O, (p < 0.0001). The PI significantly increased with PEEP incrementation, from 9% (5-15) at PEEP 0 cmH2O to 15% (5-22) at PEEP 5 cmH2O, 34% (23-44) at PEEP 10 cmH2O, and 45% (25-49) at PEEP 15 cmH2O (p < 0.001). In the present study, PI appears to be a dynamic marker of the interaction between mechanical ventilation and right heart pressure after cardiac surgery. The PI could be a useful noninvasive tool to monitor venous congestion associated with mechanical ventilation.


A system for inducing concurrent tactile and nociceptive sensations at the same site using electrocutaneous stimulation.
Studies of the interaction between mechanoception and nociception would benefit from a method for stimulation of both modalities at the same location. For this purpose, we developed an electrical stimulation device. Using two different electrode geometries, discs and needles, the device is capable of inducing two distinct stimulus qualities, dull and sharp, at the same site on hairy skin. The perceived strength of the stimuli can be varied by applying stimulus pulse trains of different lengths. We assessed the perceived stimulus qualities and intensities of the two electrode geometries at two levels of physical stimulus intensity. In a first series of experiments, ten subjects participated in two experimental sessions. The subjects reported the perceived quality and intensity of four different stimulus classes on visual analogue scales (VASs). In a second series, we added a procedure in which subjects assigned descriptive labels to the stimuli. We assessed the reproducibility of the VAS scores by calculating intraclass correlation coefficients. The results showed that subjects perceived stimuli delivered through the disc electrodes as dull and those delivered through the needles as sharp. Increasing the pulse train length increased the perceived stimulus intensities without decreasing the difference in quality between the electrode types. The intraclass correlation coefficients for the VAS scores ranged from .75 to .95. The labels that were assigned for the two electrode geometries corresponded to the descriptors for nociception and touch reported by other researchers. We concluded that our device is capable of reliably inducing tactile and nociceptive sensations of controllable intensity at the same skin site.


Skin signs in anorexia nervosa.
Anorexia nervosa (AN) is a significant cause of morbidity and mortality among adolescent females and young women. AN is associated with severe medical and psychological consequences, including death, osteoporosis, growth delay, and developmental delay. Skin signs are almost always detectable in severe AN and awareness of them may help in the early diagnosis of hidden AN. Skin signs are the expression of the medical consequences of starvation, vomiting, abuse of drugs, such as laxatives and diuretics, and of the psychiatric morbidity. They include xerosis, lanugo-like body hair, telogen effluvium, carotenoderma, acne, hyperpigmentation, seborrhoeic dermatitis, acrocyanosis, perniosis, petechiae, livedo reticularis, interdigital intertrigo, paronychia, acquired striae distensae, acral coldness.The most characteristic cutaneous sign of vomiting is Russell's sign (knuckle calluses). Symptoms due to laxative or diuretic abuse include adverse reactions by drugs. Symptoms due to psychiatric morbidity (artefacta) include the consequences of self-induced trauma. The role of the dermatologist in the management of eating disorders is to make an early diagnosis of the "hidden" signs of eating disorders in patients who tend to minimize or deny their disorder.


Gateway-Compatible CRISPR-Cas9 Vectors and a Rapid Detection by High-Resolution Melting Curve Analysis.
CRISPR-Cas9 system rapidly became an indispensable tool in plant biology to perform targeted mutagenesis. A CRISPR-Cas9-mediated double strand break followed by non-homologous end joining (NHEJ) repair most frequently results in a single base pair deletion or insertions (indels), which is hard to detect using methods based on enzymes that detect heteroduplex DNA. In addition, somatic tissues of the T1 generation inevitably contain a mosaic population, in which the portion of cells carrying the mutation can be too small to be detected by the enzyme-based methods. Here we report an optimized experimental protocol for detecting Arabidopsis mutants carrying a CRISPR-Cas9 mediated mutation, using high-resolution melting (HRM) curve analysis. Single-base pair insertion or deletion (indel) can be easily detected using this method. We have also examined the detection limit for the template containing a one bp indel compared to the WT genome. Our results show that <5% of mutant DNA containing one bp indel can be detected using this method. The vector developed in this study can be used with a Gateway technology-compatible derivative of pCUT vectors, with which off-target mutations could not be detected even by a whole genome sequencing.


Development changes in long-form leptin receptor expression and localization in rat brain.
The expression and localization of long-form leptin receptor (OB-Rb) were studied immunocytochemically in the brain of fetal and adult rats using a polyclonal antibody that specifically recognized OB-Rb. At 14 days of gestation, immunoreactive cells were observed in the ventricular layer, which contains premature neuronal cells. At 18 days of gestation, they were weakly stained but obvious in the paraventricular nucleus (PVN), and ependymal cells also showed immunoreactivity. At birth, the immunoreactivity of OB-Rb in the PVN seemed to be much lower than that in adult rats and remained low during the suckling period. Considering the presence of neuroendocrine and structural neuronal abnormalities in Lepob/Lepob mice with genetic leptin deficiency, these results suggest that the expression of OB-Rb in premature neuronal cells may have some function, and that the regulation of energy balance by leptin through hypothalamic regions, such as PVN, may not yet be developed in the perinatal period.


Prognosis after cerebral venous thrombosis: Mortality during initial admission and at 30 days and one year after discharge in a large Canadian population-based cohort.
Prognosis following cerebral venous thrombosis (CVT) is more favorable than other stroke types, but longer-term literature is limited, and trends over time are under-explored. Using administrative data, we examined factors associated with mortality in the inpatient setting, at 30 days and at one year following hospital discharge among a large consecutive cohort of Canadian patients with CVT. CVT patients from British Columbia (BC), Canada from 2000 to 2017 were identified using ICD diagnosis codes from the BC subset of the Canadian Institute for Health Information's Discharge Abstract Database. Logistic regression was used to investigate factors associated with inpatient mortality and survival analysis with Cox regression was used to explore factors associated with mortality at 30 days and one year. Of 554 incident CVT patients identified, 508 (92 %) survived their index admission. Older age (OR 1.04, 95 % CI 1.03-1.06, p < 0.01) and the presence of seizures (OR 2.31, 95 % CI 1.08-4.94, p = 0.03) or intracranial bleeding (OR 2.28, 95 % CI 1.08-4.85, p = 0.03) were associated with increased odds of inpatient mortality. Mortality after hospital discharge was 3.0 % at 30 days and 9.4 % at one year. Older age (HR 1.05, 95 % CI 1.02-1.08, p < 0.01 at 30 days; HR 1.05, 95 % CI 1.04-1.07, p < 0.01 at 1 year) and having recent or active malignancy (HR 4.17, 95 % CI 1.51-11.52, p < 0.01 at 30 days; HR 4.60, 95 % CI 2.60-8.11, p < 0.01 at 1 year) were significantly associated with higher risks of mortality at 30 days and one year after discharge. There were decreases in inpatient mortality over the study period, but this was offset by higher mortality within 30 days after discharge in the later study epochs. Among patients discharged with a diagnosis of CVT, one-year mortality was high at 9.4 %. Older age and a history of cancer were associated with higher mortality after discharge.


Second Skin as Self-Protection Against γ-Hydroxybutyrate.
γ-Hydroxybutyrate (GHB), a date-rape drug, causes certain symptoms, such as amnesia, confusion, ataxia, and unconsciousness, when dissolved in beverages and consumed by a victim. Commonly, assailants use GHB in secret for the crime of drug-facilitated sexual assault because it is tasteless, odorless, and colorless when dissolved in beverages. Generally, GHB detection methods are difficult to use promptly and secretly in situ and in real life because of the necessary detection equipment and low selectivity. To overcome this problem, we have developed a fast, simple, and easy-to-use second skin platform as a confidential self-protection platform that can detect GHB in situ or in real life without equipment. The second skin platform for naked-eye detection of GHB is fabricated with poly(vinyl alcohol) (PVA), polyurethane (PU), and polyacrylonitrile (PAN) included in the chemical receptor 2-(3-bromo-4-hydroxystyryl)-3-ethylbenzothiazol-3-ium iodide (BHEI). PAN conjugated with BHEI nanofibers (PB NFs) has various characteristics, such as ease of use, high sensitivity, and fast color change. PB NFs rapidly detected GHB at 0.01 mg/mL. Furthermore, the second-skin platform attached to the fingertip and wrist detected both 1 and 0.1 mg/mL GHB in solution within 50 s. The color changes caused by the interaction of GHB and the second skin platform cannot be stopped due to strong chemical reactions. In addition, a second skin platform can be secretly utilized in real life because it can recognize fingerprints and object temperatures. Therefore, the second skin platform can be used to aid daily life and prevent drug-facilitated sexual assault crime when attached to the skin because it can be exposed anytime and anywhere.


Management of lower extremity vascular injuries in pediatric trauma patients: a single Level I trauma center experience.
Traumatic vascular injuries of the lower extremity in the pediatric population are rare but can result in significant morbidity. We aimed at describing our experience with such complex injuries, with associated patterns of injury, diagnostic and therapeutic challenges, and outcomes. From January 2006 to December 2011, 2,844 pediatric trauma patients presented at the Ryder Trauma Center, an urban Level I trauma center in Miami, Florida. Among them, 18 patients (0.6%) were evaluated for lower extremity traumatic vascular injuries. Variables collected included age, sex, mechanism of injury, and clinical status at presentation. Surgical data included vessel injury, technical aspects of repair, associated complications, and outcomes. Mean (SD) age was ± 14.7 (2.6) years (range, 6-17 years), with 17 males (94.4%). Of the 18 traumatic pediatric patients, 32 vascular injuries were identified. All arterial injuries underwent definitive operative repair. Primary repair was performed in two patients (11.1%), six (33.3%) required saphenous vein interposition grafting as initial procedure, and eight (44.4%) underwent polytetrafluoroethylene grafting. Ligation was performed in major venous injuries and deep profunda branches. The overall survival in this series was 94.4%. Peripheral vascular injuries of the lower extremity in the pediatric population can result in acceptable outcomes if managed early and aggressively. Surgical principles of vascular surgery are similar to those applied to an adult. We recommend that these injuries should be managed in a tertiary specialized center with a multidisciplinary team of trauma surgeons, and pediatricians, which can potentially decrease morbidity and mortality. Epidemiologic study, level III.


Effects of the Long-Term Administration of Uridine on the Functioning of Rat Liver Mitochondria in Hyperthyroidism.
The effect of uridine (30 mg/kg for 7 days; intraperitoneally) on the functions of liver mitochondria in rats with experimentally induced hyperthyroidism (HT) (200 µg/100 g for 7 days, intraperitoneally) is studied in this paper. An excess of thyroid hormones (THs) led to an intensification of energy metabolism, the development of oxidative stress, a significant increase in the biogenesis, and changes in the content of proteins responsible for the fusion and fission of mitochondria. The injection of uridine did not change the concentration of THs in the blood of hyperthyroid rats (HRs) but normalized their body weight. The exposure to uridine improved the parameters of oxidative phosphorylation and corrected the activity of some complexes of the electron transport chain (ETC) in the liver mitochondria of HRs. The analysis of ETC complexes showed that the level of CI-CV did not change by the action of uridine in rats with the condition of HT. The application of uridine caused a significant increase in the activity of superoxide dismutase and lowered the rate of hydrogen peroxide production. It was found that uridine affected mitochondrial biogenesis by increasing the expression of the genes Ppargc1a and NRF1 and diminishing the expression of the Parkin gene responsible for mitophagy compared with the control animals. In addition, the mRNA level of the OPA1 gene was restored, which may indicate an improvement in the ETC activity and oxidative phosphorylation in the mitochondria of HR. As a whole, the results obtained demonstrate that uridine has a protective effect against HT-mediated functional disorders in the metabolism of rat liver mitochondria.


Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy.
The use of highly active antiretroviral therapy (HAART) has been associated with multiple metabolic complications whose pathogenesis is poorly understood at the present time. We performed a cross-sectional analysis of whole-body, lumbar spine (L1-L4) and proximal femur bone mineral density in 112 male subjects (HIV-infected patients on HAART that included a protease inhibitor, HIV-infected patients not receiving a protease inhibitor and healthy seronegative adults) using dual energy x-ray absorptiometry. Men receiving protease inhibitors had a higher incidence of osteopenia and osteoporosis according to World Health Organization definitions: relative risk = 2.19 (95% confidence interval 1.13-4.23) (P = 0.02). Subjects receiving protease inhibitors had greater central: appendicular adipose tissue ratios than the other two groups (P < 0.0001). There was no relationship between the central: appendicular fat ratio and the lumbar spine or proximal femur bone mineral density t- or z- scores, suggesting that osteoporosis and body fat redistribution are independent side effects of HAART. Osteopenia and osteoporosis are unique metabolic complications associated with protease inhibitor-containing potent antiretroviral regimens, that appear to be independent of adipose tissue maldistribution.


Admissible multiarm stepped-wedge cluster randomized trial designs.
Numerous publications have now addressed the principles of designing, analyzing, and reporting the results of stepped-wedge cluster randomized trials. In contrast, there is little research available pertaining to the design and analysis of multiarm stepped-wedge cluster randomized trials, utilized to evaluate the effectiveness of multiple experimental interventions. In this paper, we address this by explaining how the required sample size in these multiarm trials can be ascertained when data are to be analyzed using a linear mixed model. We then go on to describe how the design of such trials can be optimized to balance between minimizing the cost of the trial and minimizing some function of the covariance matrix of the treatment effect estimates. Using a recently commenced trial that will evaluate the effectiveness of sensor monitoring in an occupational therapy rehabilitation program for older persons after hip fracture as an example, we demonstrate that our designs could reduce the number of observations required for a fixed power level by up to 58%. Consequently, when logistical constraints permit the utilization of any one of a range of possible multiarm stepped-wedge cluster randomized trial designs, researchers should consider employing our approach to optimize their trials efficiency.


Undergraduate Consent Form Reading in Relation to Conscientiousness, Procrastination, and the Point-of-Time Effect.
Informed consent is central to conducting ethical research with human participants. The present study investigated differences in consent form reading in relation to conscientiousness, procrastination, and the point-of-time (PT) effect among undergraduate participants at a U.S. university. As hypothesized, conscientious participants and those who signed up to participate in a research study more days in advance and for earlier sessions (PT effect) read the consent form more thoroughly. However, procrastination was not related to consent form reading. Most importantly, consent form reading in general was poor, with 80% of participants demonstrating that they had not read the consent form. Conscientious participants were more likely to self-report reading the consent form, irrespective of their measured consent form reading. The article closes with suggestions to improve the process of obtaining informed consent with undergraduate participants.


Consensus statements from the International Society for Heart and Lung Transplantation consensus conference: Heart failure-related cardiogenic shock.
The last decade has brought tremendous interest in the problem of cardiogenic shock. However, the mortality rate of this syndrome approaches 50%, and other than prompt myocardial revascularization, there have been no treatments proven to improve the survival of these patients. The bulk of studies have been in patients with acute myocardial infarction, and there is little evidence to guide the clinician in those patients with heart failure cardiogenic shock (HF-CS). An International Society for Heart and Lung Transplant consensus conference was organized to better define, diagnose, and manage HF-CS. There were 54 participants (advanced heart failure and interventional cardiologists, cardiothoracic surgeons, critical care cardiologists, intensivists, pharmacists, and allied health professionals) with vast clinical and published experience in CS, representing 42 centers worldwide. This consensus report summarizes the results of a premeeting survey answered by participants and the breakout sessions where predefined clinical issues were discussed to achieve consensus in the absence of robust data. Key issues discussed include systems for CS management, including the "hub-and-spoke" model vs a tier-based network, minimum levels of data to communicate when considering transfer, disciplines that should be involved in a "shock team," goals for mechanical circulatory support device selection, and optimal flow on such devices. Overall, the document provides expert consensus on some important issues facing practitioners managing HF-CS. It is hoped that this will clarify areas where consensus has been reached and stimulate future research and registries to provide insight regarding other crucial knowledge gaps.


[Acne and osteoarticular manifestations].
Certain severe forms of acne vulgaris may be accompanied by disorders of the locomotor system. Fulminant acne is manifest as an acute disorder with an alteration of general health and with fever, the onset of painful, necrotic skin lesions, myalgia and arthralgia with arthritis of one or more joints. Acne conglobata, a chronic disorder, is defined by the presence of comedones in sebaceous gland ducts and its progression to form nodules and pustules, leaving indelible scars. Osteoarticular involvement which occurs during the course of acne conglobata, and whose incidence is difficult to determine, is characterized by the frequent presence of sacroiliac inflammation. However, these two forms of acne are often confused and the authors outline differences between them. A more accurate identification of cutaneous manifestations would perhaps provide an eventual classification of "rheumatic disturbances of acne" whose nosological category has not yet been determined.


Effect of isomeric structures of branched cyclic hydrocarbons on densities and equation of state predictions at elevated temperatures and pressures.
The cis and trans conformation of a branched cyclic hydrocarbon affects the packing and, hence, the density, exhibited by that compound. Reported here are density data for branched cyclohexane (C6) compounds including methylcyclohexane, ethylcyclohexane (ethylcC6), cis-1,2-dimethylcyclohexane (cis-1,2), cis-1,4-dimethylcyclohexane (cis-1,4), and trans-1,4-dimethylcyclohexane (trans-1,4) determined at temperatures up to 525 K and pressures up to 275 MPa. Of the four branched C6 isomers, cis-1,2 exhibits the largest densities and the smallest densities are exhibited by trans-1,4. The densities are modeled with the Peng-Robinson (PR) equation of state (EoS), the high-temperature, high-pressure, volume-translated (HTHP VT) PREoS, and the perturbed chain, statistical associating fluid theory (PC-SAFT) EoS. Model calculations highlight the capability of these equations to account for the different densities observed for the four isomers investigated in this study. The HTHP VT-PREoS provides modest improvements over the PREoS, but neither cubic EoS is capable of accounting for the effect of isomer structural differences on the observed densities. The PC-SAFT EoS, with pure component parameters from the literature or from a group contribution method, provides improved density predictions relative to those obtained with the PREoS or HTHP VT-PREoS. However, the PC-SAFT EoS, with either set of parameters, also cannot fully account for the effect of the C6 isomer structure on the resultant density.


Differential scanning calorimetry and fluorimetry measurements of monoclonal antibodies and reference proteins: Effect of scanning rate and dye selection.
Differential scanning calorimetry (DSC) and differential scanning fluorimetry (DSF) were used to measure the transition temperatures of four proteins: RNase A, invertase, rituximab, and the NISTmAb (NIST Reference Material, RM 8671). The proteins were combined with several different fluorescent dyes for the DSF measurements. This study compares the results of DSC and DSF measurements of transition temperatures with different types of proteins, dye combinations, and thermal scan rates. As protein unfolding is often influenced by kinetic effects, we measured the transition temperatures of the proteins using DSC over a range of temperature scan rates and compared them to the data obtained from DSF over comparable temperature scan rates. The results when the proteins were combined with Sypro Orange® and bis-ANS for the DSF measurements had the best correlations with the transition temperatures determined by calorimetry. The scan rate was found to be an important variable when comparing results between DSC and DSF. The van't Hoff enthalpy changes for the transitions were calculated from the DSC data by using a non-two-state model and from the DSF values using a two-state model. The calculated van't Hoff enthalpy changes did not show a good correlation between the two methods. © 2017 American Institute of Chemical Engineers Biotechnol. Prog., 33:677-686, 2017.


RB1 methylation by SMYD2 enhances cell cycle progression through an increase of RB1 phosphorylation.
It is well known that RB functions are regulated by posttranslational modifications such as phosphorylation and acetylation, but the significance of lysine methylation on RB has not been fully elucidated. Our expression analysis of SMYD2 by quantitative real-time polymerase chain reaction showed that expression levels of SMYD2 are significantly elevated in human bladder carcinomas compared with nonneoplastic bladder tissues (P < .0001), and its expression levels in tumor tissues were much higher than those of any other normal tissues. SMYD2 knockdown resulted in the suppression of cancer cell growth, and cell cycle analysis indicated that SMYD2 might play a crucial role in the G(1)/S transition. According to an in vitro methyltransferase assay, we found that SMYD2 methylates RB1 protein, and liquid chromatography-tandem mass spectrometry analysis revealed lysine 810 of RB1 to be methylated by SMYD2. Importantly, this methylation enhanced Ser 807/811 phosphorylation of RB1 both in vitro and in vivo. Furthermore, we demonstrated that methylated RB1 accelerates E2F transcriptional activity and promotes cell cycle progression. SMYD2 is an important oncoprotein in various types of cancer, and SMYD2-dependent RB1 methylation at lysine 810 promotes cell cycle progression of cancer cells. Further study may explore SMYD2-dependent RB1 methylation as a potential therapeutic target in human cancer.


Moving beyond cisplatin resistance: mechanisms, challenges, and prospects for overcoming recurrence in clinical cancer therapy.
Cisplatin, a classical platinum-based chemotherapy agent, has been a frontline treatment for various cancers for decades. However, its effectiveness has been hindered by the development of resistance, leading to cancer relapse. Addressing this challenge is crucial for both clinical practice and research. Hence, the imperative to unravel the intricate mechanisms underpinning cisplatin resistance and to uncover novel strategies to overcome this barrier holds immense significance. Within this review, we summarized the classification of platinum agents, highlighting their roles in therapeutic landscapes. We discussed the diverse mechanisms behind cisplatin resistance, including diminished intracellular cisplatin accumulation, intracellular detoxification, DNA repair, autophagy responses, heat shock proteins, tumor microenvironment, cancer stem cells, epigenetic regulation, ferroptosis resistance, and metabolic reprogramming. Drawing from this comprehensive understanding, we offered a series of prospective solutions to surmount cisplatin resistance and consequently mitigate the specter of disease recurrence within the realm of clinical cancer therapy.


Ivory-billed woodpecker (Campephilus principalis) persists in continental North America.
The ivory-billed woodpecker (Campephilus principalis), long suspected to be extinct, has been rediscovered in the Big Woods region of eastern Arkansas. Visual encounters during 2004 and 2005, and analysis of a video clip from April 2004, confirm the existence of at least one male. Acoustic signatures consistent with Campephilus display drums also have been heard from the region. Extensive efforts to find birds away from the primary encounter site remain unsuccessful, but potential habitat for a thinly distributed source population is vast (over 220,000 hectares).


Pericarditis as a Secondary Complication of COVID-19 in a Renal Transplant Patient.
A wide range of complications from COVID-19 are being reported, including cardiac complications. A 71-year-old woman with systemic lupus erythematosus complicated by focal segmental glomerular sclerosis status post kidney transplant presented with worsening left-sided chest pain after receiving treatment for COVID-19 pneumonia at an outside hospital. She was subsequently diagnosed with acute pericarditis, likely secondary to viral infection with COVID-19, and was successfully treated with aspirin and colchicine for 90 days without complications. NSAIDs and colchicine are mainstays in acute pericarditis treatment. Though treatment presented a potential challenge given this patient's prior kidney transplant, aspirin and colchicine proved to be effective in treating her case of COVID-19-associated pericarditis. This report has implications for future treatment of renal transplant patients with COVID-19-related pericarditis and emphasizes the need for research into the pathophysiology of pericarditis in the context of COVID-19, including risk factors and treatment.


A study of sexual satisfaction and frequency of sex among Hong Kong Chinese couples.
There have been several studies in Western societies on the causes and consequences of sexual satisfaction within marriage. Little is known, however about the marital sexual relationship in Chinese societies. Moreover, most published studies used married individuals rather than married couples as participants. The present study examined data from a well-established knowledge, attitude, and practice (KAP) survey of 1,124 Hong Kong Chinese couples on martial sexual relationship. A conceptual model was tested using structural equation modeling (SEM). Interest in sex was found to be the strongest predictor of both sexual satisfaction and frequency of sex for both husbands and wives. Among the sociodemographic variables, the following two were significantly associated with lower frequencies of sex: for wives, that of having a full-time job; and for husbands, the factor of age. Theoretical implications for research on the interplay among culture, marriage, and sex in non-Western societies are discussed.


Deep Q-Learning and Preference Based Multi-Agent System for Sustainable Agricultural Market.
Yearly population growth will lead to a significant increase in agricultural production in the coming years. Twenty-first century agricultural producers will be facing the challenge of achieving food security and efficiency. This must be achieved while ensuring sustainable agricultural systems and overcoming the problems posed by climate change, depletion of water resources, and the potential for increased erosion and loss of productivity due to extreme weather conditions. Those environmental consequences will directly affect the price setting process. In view of the price oscillations and the lack of transparent information for buyers, a multi-agent system (MAS) is presented in this article. It supports the making of decisions in the purchase of sustainable agricultural products. The proposed MAS consists of a system that supports decision-making when choosing a supplier on the basis of certain preference-based parameters aimed at measuring the sustainability of a supplier and a deep Q-learning agent for agricultural future market price forecast. Therefore, different agri-environmental indicators (AEIs) have been considered, as well as the use of edge computing technologies to reduce costs of data transfer to the cloud. The presented MAS combines price setting optimizations and user preferences in regards to accessing, filtering, and integrating information. The agents filter and fuse information relevant to a user according to supplier attributes and a dynamic environment. The results presented in this paper allow a user to choose the supplier that best suits their preferences as well as to gain insight on agricultural future markets price oscillations through a deep Q-learning agent.


The effect of running versus cycling high-intensity intermittent exercise on local tissue oxygenation and perceived enjoyment in 18-30-year-old sedentary men.
High-intensity interval training (HIIT) has been proposed as a time-efficient exercise format to improve exercise adherence, thereby targeting the chronic disease burden associated with sedentary behaviour. Exercise mode (cycling, running), if self-selected, will likely affect the physiological and enjoyment responses to HIIT in sedentary individuals. Differences in physiological and enjoyment responses, associated with the mode of exercise, could potentially influence the uptake and continued adherence to HIIT. It was hypothesised that in young sedentary men, local and systemic oxygen utilisation and enjoyment would be higher during a session of running HIIT, compared to a session of cycling HIIT. A total of 12 sedentary men (mean ± SD; age 24 ± 3 years) completed three exercise sessions: a maximal incremental exercise test on a treadmill (MAX) followed by two experiment conditions, (1) free-paced cycling HIIT on a bicycle ergometer (HIITCYC) and (2) constant-paced running HIIT on a treadmill ergometer (HIITRUN). Deoxygenated haemoglobin (HHb) in the gastrocnemius (GN), the left vastus lateralis (LVL) and the right vastus lateralis (RVL) muscles, oxygen consumption (VO2), heart rate (HR), ratings of perceived exertion (RPE) and physical activity enjoyment (PACES) were measured during HIITCYC and HIITRUN. There was a higher HHb in the LVL (p = 0.001) and RVL (p = 0.002) sites and a higher VO2 (p = 0.017) and HR (p < 0.001) during HIITCYC, compared to HIITRUN. RPE was higher (p < 0.001) and PACES lower (p = 0.032) during HIITCYC compared to HIITRUN. In sedentary individuals, free-paced cycling HIIT produces higher levels of physiological stress when compared to constant-paced running HIIT. Participants perceived running HIIT to be more enjoyable than cycling HIIT. These findings have implications for selection of mode of HIIT for physical stress, exercise enjoyment and compliance.


Computed tomography imaging and clinical characteristics of pulmonary ground-glass nodules ≤2 cm with micropapillary pattern.
The aim of this study was to investigate the imaging features, lymph node metastasis, and genetic mutations in micropapillary lung adenocarcinoma (imaging with mixed ground-glass nodules) ≤2 cm, to provide a more precise and refined basis for the selection of lung segment resection. A retrospective analysis of 162 patients with surgically resected pathologically confirmed cancers ≤2.0 cm in diameter (50 cases of micropapillary mixed ground-glass nodules [mGGNs], 50 cases of nonmicropapillary mGGNs, and 62 cases of micropapillary SNs [solid nodules]) was performed. mGGNs were classified into five categories according to imaging features. The distribution of these five morphologies in micropapillary with mGGN and nonmicropapillary with mGGN was analyzed. The postoperative pathology and prognosis of lymph node metastasis were also compared between micropapillary mGGNs and micropapillary with SNs. After searching the TCGA database, we demonstrated heterogeneity, high malignancy and high risk of microcapillary lung cancer cancers. Different pathological subtypes of mGGN differed in morphological features (p < 0.05). The rate of lymph node metastasis was significantly higher in micropapillary mGGNs than in nonmicropapillary mGGNs. In the TCGA database samples, lactate transmembrane protein activity, collagen transcription score, and fibroblast EMT score were remarkably higher in micropapillary adenocarcinoma. Other pathological subtypes had a better survival prognosis and longer disease-free survival compared with micropapillary adenocarcinoma. mGGNs ≤2 cm with a micropapillary pattern have a higher risk of lymph node metastasis compared with SNs, and computed tomography (CT) imaging features can assist in their diagnosis.


Biological and bactericidal properties of Ag-doped bioactive glass in a natural extracellular matrix hydrogel with potential application in dentistry.
The aim of this study was the fabrication and evaluation of a novel bioactive and bactericidal material, which could have applications in dentistry by supporting tissue regeneration and killing oral bacteria. Our hypothesis was that a new scaffold for pulp-dentin tissue engineering with enhanced antibacterial activity could be obtained by associating extracellular matrix derived from porcine bladder with an antibacterial bioactive glass. Our study combines in vitro approaches and ectopic implantation in scid mice. The novel material was fabricated by incorporating a sol-gel derived silver (Ag)-doped bioactive glass (BG) in a natural extracellular matrix (ECM) hydrogel in ratio 1:1 in weight % (Ag-BG/ECM). The biological properties of the Ag-BG/ECM were evaluated in culture with dental pulp stem cells (DPSCs). In particular, cell proliferation, cell apoptosis, stem cells markers profile, and cell differentiation potential were studied. Furthermore, the antibacterial activity against Streptococcus mutans and Lactobacillus casei was measured. Moreover, the capability of the material to enhance pulp/dentin regeneration in vivo was also evaluated. Our data show that Ag-BG/ECM significantly enhances DPSCs' proliferation, it does not affect cell morphology and stem cells markers profile, protects cells from apoptosis, and enhances in vitro cell differentiation and mineralisation potential as well as in vivo dentin formation. Furthermore, Ag-BG/ECM strongly inhibits S. mutans and L. casei growth suggesting that the new material has also anti-bacterial properties. This study provides foundation for future clinical applications in dentistry. It could potentially advance the currently available options of dental regenerative materials.