Flavor is in the brain.
Flavor is perhaps the most multi-modal of all of our sensory experiences. Here flavor is defined as a perception that includes gustatory, oral-somatosensory, and retronasal olfactory signals that arise from the mouth as foods and beverages are consumed. Although the sights, sounds and smells of foods that occur just before, or in the absence of eating, can impact flavor perception, it is argued that these sensory signals exert their influence by creating expectations based upon prior associations. The primary aim of the paper is to review anatomical and neurophysiological data towards an understanding of how the core sensory signals combine in the central nervous system of humans. Based upon the extant literature it is proposed that taste, oral-somatosensory and olfactory inputs are first integrated in the anterior ventral insula. The core flavor percept is then conveyed to upstream regions in the brainstem and thalamus, as well as downstream regions in the amygdala, orbitofrontal cortex and anterior cingulate cortex to produce the rich flavorful experiences that guide our feeding behavior.


Streptococcus suis synthesizes deoxyadenosine and adenosine by 5'-nucleotidase to dampen host immune responses.
Streptococcus suis is a major porcine bacterial pathogen and emerging zoonotic agent. S. suis 5'-nucleotidase is able to convert adenosine monophosphate to adenosine, resulting in inhibiting neutrophil functions in vitro and it is an important virulence factor. Here, we show that S. suis 5'-nucleotidase not only enables producing 2'-deoxyadenosine from 2'-deoxyadenosine monophosphate by the enzymatic assay and reversed-phase high performance liquid chromatography (RP-HPLC) analysis in vitro, but also synthesizes both 2'-deoxyadenosine and adenosine in mouse blood in vivo by RP-HPLC and liquid chromatography with tandem mass spectrometry analyses. Cellular cytotoxicity assay and Western blot analysis indicated that the production of 2'-deoxyadenosine by 5'-nucleotidase triggered the death of mouse macrophages RAW 264.7 in a caspase-3-dependent way. The in vivo infection experiment showed that 2'-deoxyadenosine synthesized by 5'-nucleotidase caused monocytopenia in mouse blood. The in vivo transcriptome analysis in mouse blood showed the inhibitory effect of 5'-nucleotidase on neutrophil functions and immune responses probably mediated through the generation of adenosine. Taken together, these findings indicate that S. suis synthesizes 2'-deoxyadenosine and adenosine by 5'-nucleotidase to dampen host immune responses, which represents a new mechanism of S. suis pathogenesis.


The human cytochrome b5 gene and two of its pseudogenes are located on chromosomes 18q23, 14q31-32.1 and 20p11.2, respectively.
Using very high stringency hybridization conditions for the Southern blot hybridization analysis of hamster-human cell hybrid DNA, we were able to map the human cytochrome b5 gene and two of its pseudogenes (psgb(5)1 and psgb(5)2) unambiguously to chromosomes 18, 14, and 20. These localizations were confirmed and extended to 18q23, 14q31-32.1, and 20p11.2 by using a combination of nonisotopic in situ hybridization of chromosomal spreads and the polymerase chain reaction analysis of DNA samples isolated from somatic cell hybrids retaining deletions or translocations of chromosome 18.


Oxygen supply of the blood-free perfused guinea-pig brain in normo- and hypothermia measured by the local distribution of oxygen pressure.
The O2 supply of the blood-free perfused brain cortex of the guinea pig was investigated by measuring polarographically the local distribution of tissue PO2 at 18 degrees C, 24 degrees C, and 37 degrees C. The perfusion was performed in situ, using a medium equilibrated by a gas mixture of 95% O2 and 5% CO2. Papaverine was added to prevent vasoconstriction during hypothermia. To avoid measuring artefacts thin micro electrodes with a small sharpened tip of ca. 4 microns in diameter were used and a special puncturing technique was applied. The experimental results indicate the presence of a large variation of local tissue PO2. Local mean PO2 increased up to a depth of 1000 microns, reached a plateau, and then decreased towards 3000 microns. This demonstrates that the O2 supply changes in dependence of the distance of the brain surface. This may partly be caused by the special vascularization pattern of the brain cortex. As it follows from the PO2 histograms, at 24 degrees C the tissue layer between 0-2000 microns (layer I) was well supplied with oxygen, whereas at the same time the layer between 2001-3000 microns (layer II) was hypoxic. At 37 degrees C, both layers were hypoxic, but layer III showed the more pronounced tissue hypoxia. To obtain a sufficient oxygen supply the temperature had to be reduced below 24 degrees C to sufficiently decrease tissue O2 consumption: at 18 degrees C, there was no sign of hypoxia any more. In comparison with the PO2 histogram of the tissue the PO2 histogram of the pial surface was shifted to higher PO2 values.(ABSTRACT TRUNCATED AT 250 WORDS)


Mental outcome following encephaloduroarteriosynangiosis in children with moyamoya disease with the onset earlier than 5 years of age.
The mental prognosis of children with moyamoya disease, in whom the onset was when they were younger than 5 years of age, has been reported to be very poor. We studied the mental outcome of these patients after encephaloduroarteriosynangiosis (EDAS) in relation to the age at the onset of the disease and the age at operation. For patients in whom the onset of moyamoya disease occurs when they are younger than 2 years of age, the prognosis is very poor with regard to mental abilities even if they have an operation within a year after the onset. Slight hope remains if the operation is within 3 months of the onset. For patients in whom the disease begins when they are 2-5 years of age, EDAS performed before the age of 9 years may result in a good outcome with regard to mental ability, as well as resolution of the paroxysmal symptoms and cerebral revascularization.


Intra-prostatic androgen levels during various androgen-blockade regimens.
Androgens are heavily involved in the development of prostate cancer. This article reviews the scenario of the androgen environment and androgen metabolism in the prostate during androgen-deprivation therapy (ADT) in patients with prostate cancer. Ways of altering the intra-prostatic androgen milieu during various androgen-blockade regimens include surgical castration, luteinizing hormone-releasing hormone analogues to block androgen secretion by the testes, anti-androgens, and 5alpha-reductase inhibitors. The levels of androgen precursors in the blood are different under different ADT regimens, and the androgen levels in the prostate also vary according to the ADT used. This may affect the therapeutic effect of ADT. We therefore discuss the subject of prostatic androgen levels during various androgen-blockade regimens, and we describe the prospects for the future of ADT.


Comparative Study of Tacrolimus and Short-Term Methotrexate: 2-Day versus 3-Day Methotrexate as Graft-versus-Host-Disease Prophylaxis after Umbilical Cord Blood Transplantation in Adults.
Methotrexate (MTX) in combination with a calcineurin inhibitor has been commonly used for prophylaxis of graft-versus-host disease (GVHD) following umbilical cord blood transplantation (UCBT) in Japan. However, the appropriate prophylactic MTX dosage in UCBT has not been established to date. To determine the preferential GVHD prophylaxis in UCBT, this study retrospectively investigated the administration of short-term MTX for 2 days versus 3 days. Of 103 adult patients submitted to UCBT enrolled in the study, 73 received tacrolimus (TAC) with 2 days of MTX given at 10 mg/m2 on day 1 and 7 mg/m2 on day 3 (very short-term [vs] MTX), whereas 30 patients received TAC with 3 days of MTX given at 10 mg/m2 on day 1, 7 mg/m2 on day 3, and 7 mg/m2 on day 6 (short-term [s] MTX). In univariate analysis, neutrophil engraftment was shown to be significantly better (P = .039) in the vsMTX/TAC group. Among high-risk patients, the vsMTX/TAC group also exhibited earlier neutrophil engraftment (P = .042); however, the incidence of acute GVHD was higher in the vsMTX/TAC group (P = .035) on univariate analysis. In multivariate analysis, compared with sMTX/TAC, vsMTX/TAC was associated with lower risk of relapse (hazard ratio, .27; 95% confidence interval, .11 to .64; P = .003) . These results suggest that vsMTX/TAC can be appropriate GVHD prophylaxis after UCBT, especially in higher-risk patients.


Selective inhibition of tumor microvascular permeability by cavtratin blocks tumor progression in mice.
Tumor vasculature is hyperpermeable to macromolecules compared to normal vasculature; however, the relationship between tumor hyperpermeability and tumor progression is poorly understood. Here we show that a cell-permeable peptide derived from caveolin-1, termed cavtratin, reduces microvascular hyperpermeability and delays tumor progression in mice. These antipermeability and antitumor actions of cavtratin occur in the absence of direct cytostatic or antiangiogenic effects. Cavtratin blocks microvascular permeability by inhibiting endothelial nitric oxide synthase (eNOS), as the antipermeability and antitumor actions of cavtratin are markedly diminished in eNOS knockout mice. Our results support the concepts that hyperpermeability of tumor blood vessels contributes to tumor progression and that blockade of eNOS may be exploited as a novel target for antitumor therapy.


Characterization of Early Gonadal Differentiation and Induction of Sex Reversal in the Rock Bream Oplegnathus fasciatus.
Rock bream (Oplegnathus fasciatus) is a typical fish that has a unique multiple sex chromosome system (♀X1X1X2X2/♂X1X2Y). We examined the early gonadal development in rock bream via continuous histological observations of the gonads at 40-120 days post hatching (dph). The fish was identified as a typical gonochorist, and female gonads were found to differentiate earlier than male gonads. The ovarian cavity of the female was initially observed at 80 dph, whereas the efferent duct of the male was not observed until 100 dph. Immunofluorescence with the vasa-antibody revealed that germ cells were predominantly distributed around the ovarian cavity in females and on the edge of the gonad in males during the early stages of sex differentiation. Sex reversal was induced via the oral administration of letrozole (LTZ), 17α-methyltestosterone (MT), and 17β-estradiol (E2), respectively, during the labile period of gonadal development. LTZ and MT induced 100% masculinization of genotype-females, whereas E2 induced only 50-60% feminization of genotype-males. Such findings suggest that the fish retained high sexual plasticity despite the existence of the neo-Y chromosome. MT and E2 had negative effect on fish growth, whereas LTZ did not exert such side effect. LTZ and MT could accelerate gonadal development in sex-reversed genotype-males, whereas E2 inhibited gonadal development in genotype-females of rock bream. These findings provide a basis for further research on the mechanisms of sex determination and differentiation in fishes with X1X2Y sex chromosome system and provide a sex reversal protocol for rock bream.


Systemic lupus erythematosus presenting with cardiac tamponade due to a haemorrhagic pericardial effusion.
A 14 year old girl presented with cardiac tamponade due to a haemorrhagic pericardial effusion. Systemic lupus erythematosus was diagnosed. Pericardial stripping was performed due to recurrence of the effusion despite pericardiocentesis and steroid therapy.


PM2.5 exposure associated with prenatal anxiety and depression in pregnant women.
Associations of air pollution with anxiety and depression were found in previous studies. However, whether air pollution exposure during pregnancy contributes to prenatal anxiety and depression or not is under-investigated. In this study, we aimed to analyze associations between fine particulate matter (PM2.5) exposure with anxiety and depression during pregnancy and to explore the critical window of PM2.5 exposure. This study was based on the Shanghai Maternal-Child Pairs Cohort (Shanghai MCPC). We used a gap-filling random forest model to estimate PM2.5 exposure concentration during pregnancy of each participant. The Self-Rating Anxiety Scale (SAS) and the Center for Epidemiological Survey-Depression Scale (CES-D) were used to quantify the anxiety and depression levels in late pregnancy. Covariate information was obtained from medical records and questionnaires. We performed generalized linear regression and logistic regression models to assess the association and the critical window. Totally 3731 pregnant women were included, with the age of 28.85 ± 3.97 years old. Anxiety and depression rates were 10.8 % and 11.5 % respectively, according to the cut-off value of SAS and CES-D. Generalized linear regression results showed that the increase of PM2.5 concentration in three stages (gestational 0-13 weeks, 0-26 weeks, 0-36 weeks) was related to the increase of scale score. The PM2.5 concentration in 0-13 weeks could increase the risk of anxiety and depression by approximately 23 % and 25 %, respectively. And the gestational weeks 4th-13th were the suspicious critical window of PM2.5 exposure. The increased risk of anxiety or depression was related to PM2.5 exposure during pregnancy, especially early pregnancy.


Serum phosphate and social deprivation independently predict all-cause mortality in chronic kidney disease.
Hyperphosphataemia is linked to cardiovascular disease and mortality in chronic kidney disease (CKD). Outcome in CKD is also affected by socioeconomic status. The objective of this study was to assess the associations between serum phosphate, multiple deprivation and outcome in CKD patients. All adult patients currently not on renal replacement therapy (RRT), with first time attendance to the renal outpatient clinics in the Glasgow area between July 2010 and June 2014, were included in this prospective study. Area socioeconomic status was assessed as quintiles of the Scottish Index of Multiple Deprivation (SIMD). Outcomes were all-cause and cardiovascular mortality and commencement of RRT. The cohort included 2950 patients with a median (interquartile range) age 67.6 (53.6-76.9) years. Median (interquartile range) eGFR was 38.1 (26.3-63.5) ml/min/1.73 m(2), mean (± standard deviation) phosphate was 1.13 (± 0.24) mmol/L and 31.6 % belonged to the most deprived quintile (SIMD quintile I). During follow-up 375 patients died and 98 commenced RRT. Phosphate ≥ 1.50 mmol/L was associated with all-cause (hazard ratio (HR) 2.51; 95 % confidence interval (CI) 1.63-3.89) and cardiovascular (HR 5.05; 95 % CI 1.90-13.46) mortality when compared to phosphate 0.90-1.09 mmol/L in multivariable analyses. SIMD quintile I was independently associated with all-cause mortality. Phosphate did not weaken the association between deprivation index and mortality, and there was no interaction between phosphate and SIMD quintiles. Neither phosphate nor SIMD predicted commencement of RRT. Multiple deprivation and serum phosphate were strong, independent predictors of all-cause mortality in CKD and showed no interaction. Phosphate also predicted cardiovascular mortality. The results suggest that phosphate lowering should be pursued regardless of socioeconomic status.


Efficacy of two mouth rinse sprays in inhibiting Streptococcus mutans growth on toothbrush bristles.
To compare the efficacy of two types of mouth rinse sprays (Periogard and Plax) in inhibiting the growth of Streptococcus mutans (S. mutans) on toothbrush bristles used by children. An experimental comparative study was performed. The sample included 60 children aged 6-8 years with high caries index. Children were divided randomly into 3 groups (20 each) according to materials applied on toothbrush. Each group was further subdivided into 2 subgroups A and B (10 each) according to the laboratory standards for processing microbiological specimens. Each toothbrush was placed in phosphate buffered saline, vortexed then serially diluted. Mitis salivarius bacitracin (MSB) agar plates were inoculated and incubated for 48 h. S. mutans colonies were identified by morphology, gram stain and biochemical tests. Statistically, significant difference was observed between the three groups either when toothbrushes were processed immediately or when processed after 24 h. Group I showed highest bacterial count followed by group III whereas group II showed least bacterial count. Bacterial counts were significantly decreased by time in group I and group III while in group II no significant decrease as both subgroups showed very low bacterial count. Although both mouth rinses were effective against S. mutans toothbrush contamination, chlorhexidine gluconate proved to be better.


Effects of ethanol, barbital, and lorazepam on brain monoamines in rat lines selectively outbred for differential sensitivity to ethanol.
The acute effects of ethanol, barbital, and lorazepam on the synthesis and metabolism of brain monoamines were studied in the AT (Alcohol Tolerant) and ANT (Alcohol Nontolerant) lines of rats, which have been selected for differential motor impairment after ethanol administration. The ethanol-sensitive ANT rats are also more sensitive than the ethanol-insensitive AT rats to the motor impairment caused by barbital and lorazepam. Ethanol increased, whereas barbital and lorazepam decreased, the synthesis of catecholamines in several regions of the brain. Ethanol did not affect the formation of DOPAC, whereas barbital and lorazepam reduced it. Similarly, the accumulation of 5-HTP was increased after administration of ethanol, but was decreased after administration of barbital or lorazepam. Ethanol, barbital and lorazepam decreased the formation of 5-HIAA. The rat lines did not differ in any of these responses. Some differences could, however, be demonstrated between the AT and ANT rats in the effects of the three drugs on the levels of the brain monoamines. Although the importance of these differences in the differential sensitivity to these drugs between the two lines is difficult to determine, the role of central monoaminergic mechanisms cannot be excluded. These findings also suggest that the motor impairment induced by ethanol, barbiturates, and benzodiazepines is probably not primarily based on the monoaminergic systems.


Antibiotic Prophylaxis of Surgical Site Infections in Cutaneous Surgery: A Prospective Observational Study.
The use of perioperative antibiotic prophylaxis in cutaneous surgery is controversial due to unclear efficacy and, thus, potentially unnecessary side-effects. This prospective observational study analysed the efficacy of oral perioperative antibiotic prophylaxis in preventing surgical site infections. Adult patients undergoing cutaneous surgery between August 2020 and May 2021 at Ludwig-Maximilian University Hospital Munich, Germany, without prior signs of infection were eligible. Propensity score weighting was used for covariate adjustment to account for non-randomized treatment assignment. Of 758 included patients, 23 received perioperative antibiotic prophylaxis (3.0%). In this group, a surgical site infection occurred in 1 of 45 lesions (2.2%) compared with 76 of 1,189 lesions (6.5%) in the group without perioperative antibiotic prophylaxis (735 patients, 97.0%). With covariate adjustment, the odds ratio for the occurrence of a surgical site infection in patients receiving perioperative antibiotic prophylaxis was 0.114 (95% confidence interval 0.073-0.182; p <0.001) on a per lesion level. The number of lesions needed to treat to prevent 1 surgical site infection was 17.6 (95% confidence interval 16.8-19.2). This prospective observational study shows a reduction in the incidence of surgical site infection in cutaneous surgery performed with perioperative antibiotic prophylaxis. The large size difference between the 2 study groups limits the study.


The Mini-Balance Evaluation System Test Can Predict Falls in Clinically Stable Outpatients With COPD: A 12-MO PROSPECTIVE COHORT STUDY.
This study evaluated the accuracy of the Mini-Balance Evaluation System Test (Mini-BESTest) for predicting falls in patients with chronic obstructive pulmonary disease (COPD) and investigated whether postural balance is a risk factor for falls. Postural balance was evaluated by the Mini-BESTest at baseline, and the incidence of falls over a 12-mo period was prospectively measured by a self-reported falls diary and confirmed by telephone calls. A discriminative power analysis was performed using receiver operating characteristic (ROC) curve and logistic regression analysis. Sixty-seven outpatients with COPD (mean age ± SD = 67 ± 9.3 yr) were included. Twenty-five patients (37.3%) experienced ≥1 fall, and 28.2% of the falls resulted in injuries. The Mini-BESTest predicted falls in patients with COPD at the 6- and 12-mo follow-ups with a cut-off score of 22.5 (area under the curve = 0.85 and 0.87) with good sensitivity and specificity (85.7% and 66.7%; 84% and 73.8%, respectively). Higher scores on the Mini-BESTest were associated with a lower risk of falls at 12 mo (OR = 0.50; 95% CI, 0.36-0.70; P < .001). Postural balance assessed by the Mini-BESTest is a good predictor of falls in patients with COPD. Our results imply that impaired balance contributes to the risk of falling and that balance training and fall prevention programs may be required for this population.


Migrations, trauma and mental health: A literature update on psychological assessment.
Migrants and refugees often face potentially traumatic events and post-migratory stressors. Upon arrival in the host country, they can be referred to mental health services to assess the impact of their previous experiences. These cross-cultural clinical encounters may raise questions, particularly regarding the assessment of mental health using models based on Western conceptions of psychopathology. The objective of the present non-systematic review of the literature is to discuss the psychological evaluation of post-traumatic reactions in migrants and refugees. More specifically, we present current research on psychopathology, resilience and post-traumatic development (PTG) among the migrant and refugee population. We also examine the cross-cultural validity of concepts such as Post-Traumatic Stress Disorder, resilience and PTG. Finally, we describe the most frequently used tools in cross-cultural psychological assessment and briefly reflect on the question of cultural sensitivity of mental health professionals. A bibliographic search was carried out using the databases: PILOTS, Pubmed, APA PsycNET, and Google Scholar using the following keywords: "migrants", "refugees", "posttraumatic stress disorder", "mental health", "Psychopathology", "risk factors", "protection factors", "posttraumatic growth" and "resilience". We have also reviewed the reference lists of articles encountered from database searches. Responses to a potentially traumatic situation are multiple. Regarding the migrant and refugee population, the reviewed articles studied different post-traumatic reactions such as resilience, post-traumatic development, and psychopathologies. The most studied psychopathological responses were depression, anxiety and Post-traumatic Stress Disorder. After reviewing these studies, we asked the following question: considering the complexity of the migration process, what are the factors associated with the development of these different post-traumatic responses? Indeed, several individual and social factors before, during and after migration influence the mental health of individuals in a migration situation. Among the most cited risk factors identified were: to be a victim of or witness to violence in the country of origin and, after migration, to face post-migration difficulties such as asylum denial, to be in a precarious situation with regard to housing and work, as well as the difficulties linked to adaptation to the new culture. We have also described protective factors for the mental health of this population, such as: social support, psychological support, and a good quality of life in the host country. The reviewed articles also describe an important influence of cultural aspects on mental health, such as the perception of an event as traumatic. Although the authors of the reviewed articles accept this influence of culture on post-traumatic responses, most of the tools used to assess the mental health of migrants and refugees were created in a Western context. Studies show a growing concern with these cultural aspects, and certain tools that allow a more culturally sensitive evaluation, such as the "Cultural Formulation Interview", are being developed. Even if the concern with the sensitivity of the tools used in cross-cultural assessment seems to be more present in the international literature, researchers seem to encounter difficulties in better understanding the effects of culture on the mental health of individuals. With increasingly diverse societies, new research should not be based on participants' geographic or ethnic origins, but rather try to "unpack" culture with, for example, the exploration of the relationships between certain values or orientations and the different expressions of psychological distress. Finally, given the still lacking development in the field of cross-cultural research, certain practices, such as the participation of interpreters, the supervision of cultural mediators or the use of culturally sensitive tools, can help the clinician to maintain good practices with patients from different cultures in the diagnostic and psychotherapeutical processes.


Improvements in chitosan-based slurry ice production and its application in precooling and storage of Pampus argenteus.
The effects of microbubbles in chitosan-based slurry ice production were investigated, and the efficiency of chitosan-based slurry ice was evaluated for silver pomfret (Pampus argenteus) precooling and storage at 0 °C. Microbubbles generated though agitation accelerated slurry ice production by promoting ice nucleation and eliminating supercooling. Higher bubble counts improved freezing, but overly large bubbles reduced the performance. The rheological properties of chitosan solutions were also investigaed, and solutions with higher viscosity formed more bubbles. Experiments investigating precooling rates, microbial concentrations, pH, thiobarbituric-acid-reactive substances, and total volatile basic nitrogen all confirmed that chitosan-based slurry ice had higher performance than flake ice or conventional slurry ice. Chitosan-based slurry ice can be used for precooling in the fish industry to reduce energy consumption, accelerate precooling, reduce microbial growth, and improve shelf life.


A control study to evaluate a computer-based microarray experiment design recommendation system for gene-regulation pathways discovery.
The main topic of this paper is evaluating a system that uses the expected value of experimentation for discovering causal pathways in gene expression data. By experimentation we mean both interventions (e.g., a gene knock-out experiment) and observations (e.g., passively observing the expression level of a "wild-type" gene). We introduce a system called GEEVE (causal discovery in Gene Expression data using Expected Value of Experimentation), which implements expected value of experimentation in discovering causal pathways using gene expression data. GEEVE provides the following assistance, which is intended to help biologists in their quest to discover gene-regulation pathways: Recommending which experiments to perform (with a focus on "knock-out" experiments) using an expected value of experimentation (EVE) method. Recommending the number of measurements (observational and experimental) to include in the experimental design, again using an EVE method. Providing a Bayesian analysis that combines prior knowledge with the results of recent microarray experimental results to derive posterior probabilities of gene regulation relationships. In recommending which experiments to perform (and how many times to repeat them) the EVE approach considers the biologist's preferences for which genes to focus the discovery process. Also, since exact EVE calculations are exponential in time, GEEVE incorporates approximation methods. GEEVE is able to combine data from knock-out experiments with data from wild-type experiments to suggest additional experiments to perform and then to analyze the results of those microarray experimental results. It models the possibility that unmeasured (latent) variables may be responsible for some of the statistical associations among the expression levels of the genes under study. To evaluate the GEEVE system, we used a gene expression simulator to generate data from specified models of gene regulation. Using the simulator, we evaluated the GEEVE system using a randomized control study that involved 10 biologists, some of whom used GEEVE and some of whom did not. The results show that biologists who used GEEVE reached correct causal assessments about gene regulation more often than did those biologists who did not use GEEVE. The GEEVE users also reached their assessments in a more cost-effective manner.


Dissecting disease tolerance in Plasmodium vivax malaria using the systemic degree of inflammatory perturbation.
Homeostatic perturbation caused by infection fosters two major defense strategies, resistance and tolerance, which promote the host's survival. Resistance relates to the ability of the host to restrict the pathogen load. Tolerance minimizes collateral tissue damage without directly affecting pathogen fitness. These concepts have been explored mechanistically in murine models of malaria but only superficially in human disease. Indeed, individuals infected with Plasmodium vivax may present with asymptomatic malaria, only mild symptoms, or be severely ill. We and others have reported a diverse repertoire of immunopathological events that potentially underly susceptibility to disease severity in vivax malaria. Nevertheless, the combined epidemiologic, clinical, parasitological, and immunologic features associated with defining the disease outcomes are still not fully understood. In the present study, we perform an extensive outlining of cytokines and inflammatory proteins in plasma samples from a cohort of individuals from the Brazilian Amazon infected with P. vivax and presenting with asymptomatic (n = 108) or symptomatic (n = 134) disease (106 with mild presentation and 28 with severe malaria), as well as from uninfected endemic controls (n = 128) to elucidate these gaps further. We employ highly multidimensional Systems Immunology analyses using the molecular degree of perturbation to reveal nuances of a unique profile of systemic inflammation and imbalanced immune activation directly linked to disease severity as well as with other clinical and epidemiologic characteristics. Additionally, our findings reveal that the main factor associated with severe cases of P. vivax infection was the number of symptoms, despite of a lower global inflammatory perturbation and parasitemia. In these participants, the number of symptoms directly correlated with perturbation of markers of inflammation and tissue damage. On the other hand, the main factor associated with non-severe infections was the parasitemia values, that correlated only with perturbation of inflammatory markers, such as IL-4 and IL-1β, with a relatively lower number of symptoms. These observations suggest that some persons present severe vivax regardless of pathogen burden and global inflammatory perturbation. Such patients are thus little tolerant to P. vivax infection and show higher susceptibility to disrupt homeostasis and consequently exhibit more clinical manifestations. Other persons are capable to tolerate higher parasitemia with lower inflammatory perturbation and fewer symptoms, developing non-severe malaria. The analytical approach presented here has capability to define in more details the determinants of disease tolerance in vivax malaria.


Yield and mode of diagnosis of cervical intraepithelial neoplasia 3 or cancer among women with negative cervical cytology and positive high-risk human papillomavirus test results.
In women with negative cervical cytology and positive high-risk human papillomavirus (HR-HPV) test results, we compared the risk of cervical intraepithelial neoplasia 3 (CIN 3) or cancer (CIN 3+) in women with previous abnormal cervical cytology, CIN, or HR-HPV with that in women without this history, and we determined their cumulative risk of CIN 3+. We reviewed colposcopies for negative cytology and positive HR-HPV test results from 2007 to 2009 (colposcopy was done for previous abnormal cytology, HR-HPV, or CIN or if negative cytology and positive HR-HPV test results for 20-35 months). Women with negative cytology and positive HR-HPV test results in 2007 were reviewed to determine their cumulative risk of CIN 3+. Of the 513 women with colposcopy for negative cytology and positive HR-HPV test results, 367 had previous abnormal cytology, CIN, or HR-HPV greater than 35 months ago and 146 had negative cytology and positive HR-HPV test results for 20 to 35 months. Risk of CIN 3+ for women with negative cytology and positive HR-HPV test results with previous abnormal cytology, HR-HPV, or CIN who did not have previous colposcopy was 11.9% (8/67); for similar women with previous colposcopy, it was 2.7% (8/300); and for women with positive HR-HPV test result for 20 to 35 months, it was 7.5% (11/146). In 2007 to 2009, risk of CIN 3+ for women with cytology of atypical squamous cells of undetermined significance (ASC-US) with positive HR-HPV test result was 3.9% (60/1,540). Of the 1,726 women with negative cytology and positive HR-HPV test result in 2007, 381 (22.1%) were lost to follow-up. Of the 1,345 women with median follow-up of 44 months, 602 (44.8%) had 1 or 2 subsequent negative cytology and negative HR-HPV test results and 180 had subsequent positive HR-HPV test result without biopsy. Of the 563 women with biopsy, there were 711 evaluations. Invasive cancer was found in 4 and CIN 3 in 54 (cumulative CIN 3+ of 4.3%, 58/1,345). Half (29/58) of the cumulative CIN 3+ was diagnosed after subsequent abnormal cytology and positive HR-HPV test result. If referral to colposcopy of women with cervical cytology of ASC-US and positive HR-HPV test result (CIN 3+, 3.9%) is justified, referral to colposcopy of women with negative cytology and positive HR-HPV test results is justified if they have previous abnormal cervical cytology, CIN, or HR-HPV greater than 35 months ago but have not had previous colposcopy (CIN 3+=11.9%) or are persistently HR-HPV positive for 20 to 35 months (CIN 3+, 7.5%). The risk of CIN 3+ in women with previous abnormal cytology, CIN, or HR-HPV who have previous colposcopy (2.7%) is lower because these women have incident rather than prevalent CIN 3+.


Poor allostimulatory function of liver plasmacytoid DC is associated with pro-apoptotic activity, dependent on regulatory T cells.
The liver is comparatively rich in plasmacytoid (p) dendritic cells (DC), - innate immune effector cells that are also thought to play key roles in the induction and regulation of adaptive immunity. Liver and spleen pDC were purified from fms-like tyrosine kinase ligand-treated control or lipopolysaccharide-injected C57BL/10 mice. Flow cytometric and molecular biologic assays were used to characterize their function and interaction with naturally occurring regulatory T cells (Treg). While IL-10 production was greater for freshly isolated liver compared with splenic pDC, the former produced less bioactive IL-12p70. Moreover, liver pDC expressed a low Delta4/Jagged1 Notch ligand ratio, skewed towards T helper 2 cell differentiation/cytokine production, and promoted allogeneic CD4(+)T cell apoptosis. T cell proliferation in response to liver pDC was, however, enhanced by blocking IL-10 function at the initiation of cultures. In the absence of naturally occurring CD4(+)CD25(+) regulatory T cells, similar levels of T cell proliferation were induced by liver and spleen pDC and the pro-apoptotic activity of liver pDC was reversed. The inferior T cell allostimulatory activity of in vivo-stimulated liver pDC may depend on the presence and function of Treg, a property that may contribute to inherent liver tolerogenicity.


Epinephrine improves expiratory flow rates in patients with asthma who do not respond to inhaled metaproterenol sulfate.
One hundred patients with acute asthma and peak expiratory flow rates (PEFR) less than 150 L/min were randomized and treated in a double-blind treatment protocol with either metaproterenol sulfate aerosol (MPA) inhalation and placebo injection or epinephrine injection (EPI) and inhaled placebo at entry and at 30 and 60 minutes, and then were treated with the crossover comparison regimen at 120, 150, and 180 minutes. The two groups had similar entry PEFRs and FEV1 (MPA, 112 L/min; 0.94 L, respectively; EPI, 111 L/min; 0.85 L, respectively) and similar plasma theophylline levels (MPA, 12.2 micrograms/ml; EPI, 13.8 micrograms/ml). PEFR and FEV1 were measured every 30 minutes for 4 hours. Mean expiratory flow rates among both groups were similar at entry and at 120 and 240 minutes. At 120 minutes, flow rates had improved in 28/46 MPA-treated patients (61%) and 48/54 EPI-treated patients (89%). Among these improved patients, flow rates were significantly higher in the MPA-treated group. At 120 minutes, 18/46 MPA-treated patients (39%) and 6/54 EPI-treated patients (11%) had PEFRs less than 120 L/min and PEFR and FEV1 less than 120% of baseline values (p less than 0.01). In 13 of these 18 MPA-treated patients who did not improve compared to 1/6 EPI-treated patients who did not improve, PEFRs were greater than 120 L/min, and PEFR and FEV1 had increased 20% or more above baseline values after treatment with the crossover comparison regimen (p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)


PAK2/beta-catenin/c-Myc/PKM2 signal transduction suppresses ovarian granulosa cell apoptosis in polycystic ovary syndrome.
Polycystic ovary syndrome (PCOS) exhibits the highest morbidity among endocrine diseases in women ranging from age 18 to 44. However, its pathogenesis remains unclear. The imbalance between systemic and ovarian oxidative stress (OS) is a key characteristic of PCOS, and accumulating evidence indicates that the antioxidative protein nuclear factor erythroid-2-related factor 2 (Nrf2) is implicated in cell apoptosis and inflammation caused by OS. The activated kinase 2 (PAK2)/-catenin/c-Myc/pyruvate kinase M2 (PKM2) axis is a newly identified signaling pathway that may regulate Nrf2 expression and thereby influence OS. In this study, we sought to identify PAK2 expression and function in PCOS cells. PAK2 and downstream PKM2 expression in KGN cells and tissues were detected by microarray and qPCR. Cell viability was determined using CCK-8 and colony formation assays (CFAs). Apoptosis was examined by flow cytometry. qPCR and ELISA were used to examine cell inflammation. Oxidant and OS-related enzymes were examined by ELISA. We found that PAK2 and PKM2 expression levels were reduced in KGN cells and PCOS ovarian cortex tissues. PAK2 overexpression activated β-catenin/c-Myc/PKM2 while PAK2 silencing deactivated it. PAK2 overexpression was reduced, whereas PAK2 silencing promoted, KGN cell proliferation and colony formation. Cell apoptosis and inflammation were also induced by PAK2 overexpression but were alleviated by its silencing. Furthermore, increased peroxidation product levels decreased antioxidative protein activities, and deactivated antioxidative Nrf2/HO-1 pathway were detected in PAK2-overexpressing KGN cells, whereas these effects were counteracted in PAK2 silenced cells. Our data suggest that PAK2 and its associated β-catenin/c-Myc/PKM2 inhibited cell viability and induced apoptosis and inflammation by triggering OS by deactivating the Nrf2/HO-1 pathway, suggesting the potential of PAK2 as a therapeutic PCOS treatment target.


[People with dementia in acute hospitals. Literature review of prevalence and reasons for hospital admission].
People with dementia who are hospitalized depend on hospital care that is tailored to their particular needs. However, the current structural conditions and standardized care plans are often opposed to the needs for familiarity and orientation that people with dementia have. For the development of dementia-specific care concepts, it is important to know the proportion of persons with dementia who are hospitalized as well as the diagnosis that leads to hospital admission. The results of the literature review show prevalence estimates of 3.4-43.3%. The probability or risk of hospitalization for persons with dementia is between 1.4-3.6 times greater than it is for non-dementia persons. In addition, the reasons for admission are different. People with dementia are more frequently hospitalized due to infectious diseases, fractures, or nutritional disorders than non-dementia persons. Based on these results, one can hypothesize that there is a need for cross-sectoral care approaches, since these indicate the necessity for further research in order to establish a reliable database.


In contrast to dogs, red foxes (Vulpes vulpes) did not shed neospora caninum upon feeding of intermediate host tissues.
To clarify whether red foxes (Vulpes vulpes) can be final hosts of Neospora caninum, foxes and dogs were fed in parallel on tissues of a sheep and a goat experimentally infected with N. caninum. The faeces of at least two of five dogs contained N. caninum oocysts, as determined by bioassay. In the faeces of all six foxes fed in parallel, oocysts were detected that were larger in size (length 12.6 +/- 0.5 microm, width 11.8 +/- 0.4 microm) than the oocysts shed by the dogs. Ribosomal RNA sequences and the results of an immunoblot-based bioassay provided further evidence that these oocysts were different from N. caninum. A titration experiment performed to determine the sensitivity of a bioassay utilising gerbils showed that as few as five sporulated N. caninum oocysts could be detected by this test. This indicates that, in two feeding experiments, less than 3,700 and 200 sporulated N. caninum oocysts, respectively, could have been among the Hammondia sp.-like oocysts collected from fox faeces. These results suggest that the red fox is either an inappropriate final host for N. caninum or not at all a final host for this parasite.


Phase II study of intraoperative dosimetry for prostate brachytherapy using registered ultrasound and fluoroscopy.
To assess the performance of a system of intraoperative dosimetry and obtain estimates of dosimetry outcomes achieved when utilizing the system in a Phase II clinical trial. Forty-five patients undergoing permanent Pd-103 seed implantation for prostate cancer were prospectively enrolled. Seed implantation was performed and dose was tracked intraoperatively using intraoperative registered ultrasound and fluoroscopy (iRUF). Three-dimensional seed locations were computed from X-rays and registered to ultrasound for intraoperative dosimetry, followed by adaptive plan modification to achieve prostate V100 ≥95% and ≥95% D90. Time required for iRUF was recorded. Postoperative CT/MRI scans were performed 1 day after the implantation and used as reference for dosimetric analysis. Dosimetric parameters for the prostate and urethra were compared between standard ultrasound-based dosimetry (USD), iRUF, and postoperative CT/MRI. Mean total time for iRUF was <30 min. A mean of four seeds (0-12) were added per implant to correct cold spots discovered by iRUF. Day 1 CT/MRI prostate V100 was ≥95% for 44/45 patients; 1 patient had Day 1 V100 93%. No patient had rectal V100 exceeding 1 cc. Compared to CT/MRI, iRUF dosimetry had significantly smaller mean differences and higher correlations for all prostate and urethral dosimetric parameters examined than USD. Both USD and iRUF tended to overestimate dose, but with less bias in iRUF than USD. Intraoperative dosimetry utilizing iRUF was associated with acceptable increase in procedure time and enabled very high rates of achieving excellent prostate dose coverage. iRUF intraoperative dosimetry approximated postoperative CT/MRI dosimetry to a greater degree than USD for the prostate and urethra.


Phosphorylation of the amino-terminal head domain of the middle molecular mass 145-kDa subunit of neurofilaments. Evidence for regulation by second messenger-dependent protein kinases.
To begin to understand the regulation and roles of neurofilament phosphorylation, we localized the phosphorylated domains on the 140-145-kDa neurofilament subunit (NF-M) and identified the protein kinases that may specifically phosphorylate the sites within these domains in vivo. Mouse retinal ganglion cells were labeled in vivo by injecting mice intravitreally with [32P]orthophosphate, and neurofilament-enriched fractions were obtained from the optic axons. Two-dimensional phosphopeptide map analysis of NF-M after digestion with alpha-chymotrypsin and trypsin revealed seven major (M8-M14) and at least eight minor (M1-M7 and M15) phosphopeptides. Two-dimensional phosphopeptide map analyses of NF-M phosphorylated in vitro by individual purified or endogenous axonal cytoskeleton-associated protein kinases showed that five peptides (M9-M13) were substrates for the heparin-sensitive second messenger-independent protein kinase(s). Protein kinase A and/or protein kinase C phosphorylated eight other peptides (M1-M8). Two alpha-chymotryptic peptides (C1 and C2) that were phosphorylated by protein kinase A but not by the endogenous independent kinase(s) were isolated by high performance liquid chromatography on a reverse-phase C8 column. Partial sequence analysis of peptides C1 (S R V S G P S ...) and C2 (S R G S P S T V S ...) showed that the peptides were localized on the head domain of NF-M at 25 and 41 residues from the amino terminus, respectively. Tryptic digest of peptide C1 (less than 12 kDa) generated the phosphopeptides M1-M6. Peptide C2 was a breakdown product of peptide C1. Since the polypeptide sites targeted by second messenger-independent kinase(s) associated with neurofilaments are localized on the carboxyl-terminal domain, separate aspects of NF-M function appear to be regulated by separate kinase systems that selectively phosphorylate head or tail domains of the polypeptide.


Discoid lupus erythematosus-like eruption induced by infliximab.
Lupus erythematosus-like syndromes have been reported as an adverse effect of anti-tumour necrosis factor-alpha therapy. We report the case of a patient with rheumatoid arthritis who developed a discoid lupus erythematosus-like eruption after treatment with infliximab. The rash consisted of diffuse scaly erythematous plaques on the face, trunk and extremities, and occurred in the context of elevated anti-nuclear and anti-double-stranded DNA antibody titres. Direct immunofluorescence of lesional skin showed linear deposition of IgG, IgM and C3. The lesions resolved completely after the discontinuation of infliximab and with the use of anti-malarial therapy. We discuss the clinical, histological and immunohistochemical features of this case and review the literature with respect to the incidence of lupus erythematosus-like syndromes in patients receiving tumour necrosis factor-alpha antagonists.


Quantitative analysis of the viscoelastic properties of thin regions of fibroblasts using atomic force microscopy.
Viscoelasticity of the leading edge, i.e., the lamellipodium, of a cell is the key property for a deeper understanding of the active extension of a cell's leading edge. The fact that the lamellipodium of a cell is very thin (<1000 nm) imparts special challenges for accurate measurements of its viscoelastic behavior. It requires addressing strong substrate effects and comparatively high stresses (>1 kPa) on thin samples. We present the method for an atomic force microscopy-based microrheology that allows us to fully quantify the viscoelastic constants (elastic storage modulus, viscous loss modulus, and the Poisson ratio) of thin areas of a cell (<1000 nm) as well as those of thick areas. We account for substrate effects by applying two different models-a model for well-adhered regions (Chen model) and a model for nonadhered regions (Tu model). This method also provides detailed information about the adhered regions of a cell. The very thin regions relatively near the edge of NIH 3T3 fibroblasts can be identified by the Chen model as strongly adherent with an elastic strength of approximately 1.6 +/- 0.2 kPa and with an experimentally determined Poisson ratio of approximately 0.4 to 0.5. Further from the edge of these cells, the adherence decreases, and the Tu model is effective in evaluating its elastic strength ( approximately 0.6 +/- 0.1 kPa). Thus, our AFM-based microrheology allows us to correlate two key parameters of cell motility by relating elastic strength and the Poisson ratio to the adhesive state of a cell. This frequency-dependent measurement allows for the decomposition of the elastic modulus into loss and storage modulus. Applying this decomposition and Tu's and Chen's finite depth models allow us to obtain viscoelastic signatures in a frequency range from 50 to 300 Hz, showing a rubber plateau-like behavior.


Pharmacokinetic study of a patient intoxicated with 2,4-dichlorophenoxyacetic acid and 2-methoxy-3,6-dichlorobenzoic acid.
A simultaneous pharmacokinetic study of two chemicals has been conducted on a clinically stabilized human who had intentionally ingested a mixture of 2,4-D and Dicamba. The information developed can be useful to the clinical toxicilogist in the management of similar cases.


Influence of orthosis on the foot progression angle in children with spastic cerebral palsy.
We retrospectively assessed the effect of ankle-foot orthosis (AFO) on the foot progression angle (FPA) of 97 children with spastic cerebral palsy (CP) who had undergone comprehensive computer-based gait analysis both barefoot and with their orthosis, during the same session. The physical examination results and the gait study temporal and kinematic parameters comprise the study data. We focused on the peak FPA reached during stance and swing phases and at mid-stance and mid-swing, and also measured the transverse rotations of the pelvis, the femur and the tibia. AFOs improved gait, as reflected by improved temporal parameters, but they also increased internal rotation of the feet in diplegic CP children by 4.29 degrees for mid-stance, and by 3.72 degrees for mid-swing. The correlation between components of the rotational profile and FPA was significant for the diplegic group. AFOs did not produce any noteworthy differences between walking barefoot and walking with the brace in the hemiplegic group in what concerns FPA. Children with diplegic CP who use AFOs walk with increased internal FPAs in their orthoses. These findings might be explained by anatomical attributes as well as dynamic features during gait.


Extended reality in surgical education: A systematic review.
This review aims to evaluate the effectiveness of extended reality-based training in surgical education. This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. A total of 33 studies were included in the qualitative analysis. Nine studies evaluated the effectiveness of virtual reality-based training against no substitutional training. Seven studies looked at training for laparoscopic surgery, and the results were contradicting. Two studies focused on orthopedics training, and the outcomes were positive. Fourteen studies compared the outcomes of virtual reality-based training to conventional didactic teaching, all demonstrating superior outcomes for virtual reality-based training. Nine studies compared the outcomes of virtual reality simulation training to dry lab simulation training. The inferior outcomes of virtual reality simulation training were demonstrated by 5 studies for laparoscopic surgery, 1 study for arthroscopic procedures, 1 study for robotic surgery, and 1 study for dental procedures. One study found potential benefits of virtual reality simulation training on orthopedics surgeries. One study found virtual reality simulation training to be superior to cadaveric training, and 3 studies found augmented reality and virtual reality-based training to be comparable to supervised operative opportunities. Extended reality-based training is a potentially useful modality to serve as an adjunct to the current physical surgical training.


Influence of Acute Normobaric Hypoxia on Hemostasis in Volunteers with and without Acute Mountain Sickness.
The aim of the present study was to investigate whether a 12-hour exposure in a normobaric hypoxic chamber would induce changes in the hemostatic system and a procoagulant state in volunteers suffering from acute mountain sickness (AMS) and healthy controls. 37 healthy participants were passively exposed to 12.6% FiO2 (simulated altitude hypoxia of 4,500 m). AMS development was investigated by the Lake Louise Score (LLS). Prothrombin time, activated partial thromboplastin time, fibrinogen, and platelet count were measured and specific methods (i.e., thromboelastometry and a thrombin generation test) were used. AMS prevalence was 62.2% (LLS cut off of 3). For the whole group, paired sample t-tests showed significant increase in the maximal concentration of generated thrombin. ROTEM measurements revealed a significant shortening of coagulation time and an increase of maximal clot firmness (InTEM test). A significant increase in maximum clot firmness could be shown (FibTEM test). All significant changes in coagulation parameters after exposure remained within normal reference ranges. No differences with regard to measured parameters of the hemostatic system between AMS-positive and -negative subjects were observed. Therefore, the hypothesis of the acute activation of coagulation by hypoxia can be rejected.


Silk-hydrogel Lenses for Light-emitting Diodes.
Today the high demand for electronics leads to massive production of waste, thus green materials based electronic devices are becoming more important for environmental protection and sustainability. The biomaterial based hydrogels are widely used in tissue engineering, but their uses in photonics are limited. In this study, silk fibroin protein in hydrogel form is explored as a bio-friendly alternative to conventional polymers for lens applications in light-emitting diodes. The concentration of silk fibroin protein and crosslinking agent had direct effects on optical properties of silk hydrogel. The spatial radiation intensity distribution was controlled via dome- and crater-type silk-hydrogel lenses. The hydrogel lens showed a light extraction efficiency over 0.95 on a warm white LED. The stability of silk hydrogel lens is enhanced approximately three-folds by using a biocompatible/biodegradable poly(ester-urethane) coating and more than three orders of magnitude by using an edible paraffin wax coating. Therefore, biomaterial lenses show promise for green optoelectronic applications.


Asymptotic State of a Two-Patch System with Infinite Diffusion.
Mathematical theory has predicted that populations diffusing in heterogeneous environments can reach larger total size than when not diffusing. This prediction was tested in a recent experiment, which leads to extension of the previous theory to consumer-resource systems with external resource input. This paper studies a two-patch model with diffusion that characterizes the experiment. Solutions of the model are shown to be nonnegative and bounded, and global dynamics of the subsystems are completely exhibited. It is shown that there exist stable positive equilibria as the diffusion rate is large, and the equilibria converge to a unique positive point as the diffusion tends to infinity. Rigorous analysis on the model demonstrates that homogeneously distributed resources support larger carrying capacity than heterogeneously distributed resources with or without diffusion, which coincides with experimental observations but refutes previous theory. It is shown that spatial diffusion increases total equilibrium population abundance in heterogeneous environments, which coincides with real data and previous theory while a new insight is exhibited. A novel prediction of this work is that these results hold even with source-sink populations and increasing diffusion rate of consumer could change its persistence to extinction in the same-resource environments.


An attempt at data verification in the EACTS Congenital Database.
The multi-national and multi-institutional collection of data on outcomes in Congenital Heart Surgery (CHS) provides the possibility of analysis of results of treatment and may result in further improvement of the quality of care. The verification of data as far as the completeness and accuracy is necessary to give confidence to all sides--the patients, centers and regulatory authorities. The source data verification (SDV), although difficult, appears possible even in such a large-scale database. Out of 5.274 patients and 5.612 procedures data of 2003, collected in the database, 1.703 (32.3%) and 1.895 (33.8%), respectively, have been verified at five sites on following fields: IPPV time, date of birth, date of admission, date of surgery, date of discharge/mortality, body weight, case category, CPB time, AoX time, Circulatory arrest time. SDV was performed at five sites by two database officers using the sources of information different to the local copy of the database (patients' files, operation notes, perfusion charts, OR Books). Verification was performed between June 1st and July 31st 2004. Statistical analysis was performed using R-project software, ver. 2.0.0. and Welch's t-test for comparison of continuous variables. P-value >0.05 was used as statistically significant difference between groups. Pre- and post-verification mortalities in all groups showed no significant differences although seven deaths out of 68 (10.27%) were missed. None of the other verified fields showed significant differences after verification. Source Data Verification showed no statistically significant differences between verified and non-verified data on 30 days mortality, LOS, age, body weight, CPB time, AoX and Circulatory arrest time. IPPV time was not available in 58.6% procedures.


The effect of Brain Gym on cognitive function in older people: A systematic review and meta-analysis.
This review aimed to systematically evaluate and meta-analyze the available data on the effects of Brain Gym (BG) on cognitive function in older people. Six electronic databases were searched systematically using: "Brain Gym" AND "elderly, "Brain Gym" AND "older people". The PEDro and MINORS scales were used to evaluate methodological quality. For the meta-analysis, inverse variance or generic inverse variance was used and heterogeneity was assessed with the Chi2 test and I2 test. Ten research studies with a high to low quality. Significant changes intra- and inter-group were observed for neurocognitive outcomes in the BG groups. Findings from the metaanalysis indicated changes in the BG groups, on cognitive function by means of the Mini-Mental State Examination, were not greater than those reported in the control/comparison groups. BG will not lead to improvements in cognitive function in people with and without cognitive impairment, supported by low to high evidence.


Activation of the hemostatic system during thrombolytic therapy.
Activation of the hemostatic mechanism has been described during thrombolytic therapy. This phenomenon has been detected by new methods of assessing hemostatic system function, based on immunoenzymatic or radioimmunoassays. However, these methods are extremely sensitive and, unless they are performed in expert laboratories, carefully following the recommended procedures, they generate in vitro artifacts. A description of these methods is provided, as well as a critical review of the available studies. The correct use of these methods will provide us with an understanding of the complex response of the hemostatic system to pharmacologic thrombolysis.


MiR-144-5p/CCL12 Signaling Axis Modulates Ischemic Preconditioning-Mediated Cardio-protection by Reducing Cell Viability, Enhancing Cell Apoptosis, Fibrosis, and Pyroptosis.
Ischemic postconditioning (IPost) represents short periods of nonlethal ischemia-reperfusion performed at the onset of reperfusion. Studies have shown that IPost involves various biological processes such as cell proliferation, apoptosis, and pyroptosis and can activate complex signaling pathways. CCL12 is a critical mediator in the inflammatory process after tissue injury. In the present study, we examined the potential actions of CCL12-mediated signaling pathways in cardioprotection after IPost using a cardiomyocyte model. By applying the bioinformatics analysis, we found that CCL12 was upregulated in the rat heart tissues after I/R injury, and the expression level of CCL12 was restored in rats with IPost. The in vitro studies showed that CCL12 and CCR2 expression levels were upregulated in the hypoxia/reoxygenation (H/R)-induced H9C2 cells, which was attenuated in the H/R + hypoxia post-conditioning (PostC) group. The functional assays showed that H/R treatment reduced cell viability, increased cell apoptosis, and promoted fibrosis and pyroptosis of H9C2 cells, which was attenuated in the H/R + PostC group. Overexpression of CCL12 impaired the protective action of hypoxia post-conditioning in the H9C2 cells. Further mechanistic studies showed that miR-144-5p could directly target the 3' untranslated region of CCL12. Overexpression of miR-144-5p markedly repressed the expression levels of CCL12 and CCR2 in H9C2 cells, while miR-144-5p inhibition had the opposite effects. Furthermore, the inhibition of miR-144-5p reduced the cell viability, increased cell apoptosis, and enhanced fibrosis and pyroptosis of H9C2 cells after H/R or H/R + PostC treatment. In conclusion, CCL12 was downregulated in cardiomyocytes following ischemic postconditioning, and CCL12 overexpression impaired the cardioprotective actions of ischemic postconditioning by reducing cell viability, enhancing cell apoptosis, fibrosis, and pyroptosis. Further mechanistic evidence revealed that CCL12 was a direct target of miR-144-5p, and miR-144-5p/CCL12/CCR2 signaling may represent a critical pathway in mediating the cardioprotective effects of ischemic postconditioning.


Second neoplasm: a complication of cancer treatment.
Two cases of second tumors induced by chemo and/or radiotherapy used in the treatment of gynecological neoplasms, are described. A comparison with data reported in the Literature was performed.


Heterogeneity of apex-to-base dispersion in diastolic lengthening is related to impaired global left ventricular relaxation in patients with hypertrophic cardiomyopathy.
The presence of apex-to-base disparity in diastolic left ventricle (LV) endocardial lengthening, based on an electromechanical activation sequence, has been recognized as an important determinant of LV diastolic properties. However, the behavior of LV apical and basal diastolic lengthening and its relationship to LV filling in hypertrophic cardiomyopathy (HCM) are unknown. We obtained basal and apical LV short-axis views in 27 patients with non-obstructive HCM and 25 healthy volunteers. The patients with HCM were subdivided into two groups; those with apical hypertrophy [APH(+)] or those without apical hypertrophy [APH(-)]. Eight equiangular points on the endo-myocardium at end diastole were placed in each view, and the movements of these points were automatically tracked using a two-dimensional echocardiographic tissue tracking system. Time-LV internal diameter curves were obtained and averaged. The time intervals from the aortic valve closure to the point of the first 40% of peak diastolic lengthening (T 40) were measured in each view. The standard deviation of the time to peak systolic circumferential shortening at the base and apex were calculated to assess the heterogeneity of LV contraction. The time difference in the T 40 between the apex and base (dt-T 40) in the HCM-APH(+) and HCM-APH(-) groups was greater than that in the control group. The heterogeneities in LV apical systolic shortening in the HCM groups were greater than those in the control group. There were good linear correlations between the dt-T 40 and the LV early diastolic echo-parameters and the LV mass index. Delayed apical relaxation and filling in patients with HCM is related to LV diastolic dysfunction and systolic dyssynchronous contraction.


Effects of new antiarrhythmic agent SS-68 on excitation conduction, electrical activity in Purkinje fibers and pulmonary veins: Assessment of safety and side effects risk.
The compound SS-68 has been selected among numerous new derivatives of indole and demonstrated antiarrhythmic effects in animal models. The present study concerns several aspects of SS-68 safety and efficacy as a potential antiarrhythmic drug. The first estimation of atrioventricular conduction in mammalian heart under SS-68 has been carried out; effects of SS-68 in Purkinje fibers and myocardium of pulmonary veins have been investigated. The drug weakly affects cardiac atrioventricular conduction: only high concentrations of SS-68 (≥10 μmol/L) significantly decrease this parameter. Also, the drug weakly affects Purkinje fibers automaticity, but effectively alters action potential waveform in Purkinje fibers in a concentration-dependent manner. SS-68 (0.1-100 μmol/L) failed to induce any early or delayed afterdepolarizations in Purkinje fibers both in basal conditions and under provocation of proarrhythmic activity by norepinephrine (NE). Moreover, 10 μmol/L SS-68 suppressed NE-induced extra-beats and rapid firing in Purkinje fibers. In pulmonary veins only high concentrations of SS-68 significantly increased action potential duration, while lower concentrations (0.1-1 μmol/L) were ineffective. Also, 0.1-100 μmol/L SS-68 was unable to elicit arrhythmogenic alternations of action potential waveform in pulmonary veins. In conclusion, SS-68 has no proarrhythmic effects, such as afterdepolarizations or abnormal automaticity in used experimental models.


Cholecystokinin appears to have antipsychotic properties.
1. According to a currently popular biological hypothesis schizophrenic symptoms are caused by a hyperactivity in dopaminergic neurotransmission. Since cholecystokinin (CCK) is a neuromodulator of dopaminergic neurotransmission, the effects of CCK (0.3 microgram/kg; given in a single dose intravenously) were studied in six chronic paranoid schizophrenic patients. 2. Following 3 baseline assessments on separate days, the effects of CCK treatment were assessed immediately after the injection, daily for one week and weekly thereafter for 5 weeks by the Brief Psychiatric Rating Scale (BPRS) and by the Schizophrenia Subscale of the Present State Examination (SS-PSE). 3. One way analysis of variance revealed statistically significant changes in all BPRS factors as well as in the nuclear syndrome and in the total score of the SS-PSE. Dunnett's tests revealed that the time at which the changes from baseline became statistically significant was as follows: anxiety-depression factor of the BPRS, immediately after the injection; anergia factor of the BPRS, by day 2; thought disturbance factor of the BPRS, immediately after; activation factor of the BPRS, immediately after; hostile-suspiciousness factor of the BPRS, by day 1; total BPRS score, immediately after; nuclear syndrome of the SS-PSE, by day 1; and total score of the SS-PSE, by day 1. 4. It is concluded that further controlled studies of the antipsychotic properties of CCK are warranted.


Abnormal radiological findings and a decreased carbon monoxide transfer factor can persist long after the acute phase of Legionella pneumophila pneumonia.
Pulmonary abnormalities may persist long after the acute phase of legionnaires disease (LD). In a cohort of 122 survivors of an outbreak of LD, 57% were still experiencing an increased number of symptoms associated with dyspnea at a mean of 16 months after recovery from acute-phase LD. For 86 of these patients, additional evaluation involving high-resolution computed tomography (HRCT) of the lung revealed pulmonary abnormalities in 21 (24%); abnormal HRCT findings generally presented as discrete and multiple radiodensities. Residual pulmonary abnormalities were associated with a mean reduction of 20% in the gas transport capacity of the lung. This latter sign could not be used to explain the increased symptoms of dyspnea reported by patients. Receipt of mechanical ventilation during the acute phase of LD, delayed initiation of adequate antibiotic therapy, and chronic obstructive pulmonary disease were identified as risk factors for the persistence of lung abnormalities.


Organophosphate pesticide-induced toxicity through DNA damage and DNA repair mechanisms.
Organophosphate pesticides (OPs) are widely used in agriculture, healthcare, and other industries due to their ability to kill pests. However, OPs can also have genotoxic effects on humans who are exposed to them. This review summarizes the research on DNA damage caused by OPs, the mechanisms behind this damage, and the resulting cellular effects. Even at low doses, OPs have been shown to damage DNA and cause cellular dysfunction. Common phenomena seen in cells that are exposed to OPs include the formation of DNA adducts and lesions, single-strand and double-strand DNA breaks, and DNA and protein inter and intra-cross-links. The present review will aid in comprehending the extent of genetic damage and the impact on DNA repair pathways caused by acute or chronic exposure to OPs. Additionally, understanding the mechanisms of the effects of OPs will aid in correlating them with various diseases, including cancer, Alzheimer's, and Parkinson's disease. Overall, knowledge of the potential adverse effects of different OPs will help in monitoring the health complications they may cause.


Combination of HLA-Matched Sibling Allogeneic Hematopoietic Stem Cell Transplantation With Unrelated Cord Blood Unit in Patients Aged 35 to 50 Years With Severe Aplastic Anemia: Preliminary Summary of a Single-Arm Trial.
This study reports a single-arm trial in the interim phase in 4 patients with median age of 40.5 years who have undergone combined HLA-matched sibling donor (MSD) stem cell graft and an unrelated cord blood (UCB) unit for the treatment of severe aplastic anemia (SAA). The median time was 10 days for neutrophil engraftment (9-18 days) and 17 days for platelets (12-24 days). Median follow-up of 22 months (ranging from 16 to 29 months) showed survival of the 4 patients with complete hematological response. Acute graft-vs-host disease (GVHD) (grade II) occurred only in 1 patient, yet chronic GVHD was free. One patient showed a pattern of transient MSD graft followed by dominant UCB chimerism, and another 1 achieved mixed chimerism in the first 6 months after allogeneic hematopoietic stem cell transplantation (allo-HSCT) then evolved to a stable MSD graft. The other 2 patients sustained a full MSD graft during the post-HSCT period. Nevertheless, none of the patients developed primary and secondary graft failure up to the final follow-up. Although this is a small cohort, the dual transplantation combining HLA-matched sibling allogeneic hematopoietic stem cell transplantation with unrelated cord blood unit may deserve further exploration for treatment of SAA patients aged 35 to 50 years old.


Analysis of microstructural parameters of trabecular bone based on electrical impedance spectroscopy and deep neural networks.
The potential of electrical impedance spectroscopy (EIS) was demonstrated for the investigation of microstructural properties of osseous tissue. Therefore, a deep neural network (DNN) was implemented for a sensitive assessment of different structural features that were derived on the basis of dielectric parameters, especially relative permittivities, recorded over a frequency range from 40 Hz to 5 MHz. The advantages of the developed method over conventional approaches, including equivalent circuit models (ECMs), linear regression and effective medium approximation (EMA), is the comprehensive quantification of bone morphologies by several microstructural parameters simultaneously, such as bone volume fraction (BV/TV), bone surface-volume-ratio (BS/BV), structure model index (SMI), trabecular number (Tb.N) and trabecular thickness (Tb.Th). The comparison of predictions of the DNN with an analysis of µCT-images confirmed a high accuracy for different microstructural parameters, which was indicated by corresponding Pearson correlation coefficients, especially for Tb.Th (r = 0.89) and BS/BV (r = 0.80). Concurrently, the approach was able to unambiguously discriminate anatomically similar bone regions (femoral head, greater trochanter and femoral neck) and therefore was capable to determine the morphological status of osseous tissue in detail. The classification was more discriminative than one based on classical linear discriminant analysis (LDA), due to the distinguishing features extracted by the DNN model. Accordingly, the method and model can serve as a potential tool for evaluating bone quality and bone status.


Assessing the mental effects of COVID-19-related work on depression among community health workers in Vietnam.
Community health workers (CHWs) involved in the COVID-19 response might be at increased risk of developing depression, though evidence is scarce. We investigated effects of COVID-19-related work on changes in depression levels among CHWs in Vietnam and identified sub-groups among CHWs who are at particular risk of developing severe depression. We conducted a cross-sectional online survey among 979 CHWs who were involved in the COVID-19 response in Vietnam, in particular during the 2021 Tet holiday outbreak between January and March 2021. Respondents were asked to report depression symptoms at two-time points, before the start of the COVID-19 pandemic (average June to December 2019) and during the 2021 Tet holiday outbreak using the PHQ-9 mental health questionnaire. We estimated depression levels at both time points and developed univariate and multivariable logistic regression models to estimate odds ratios and 95% confidence intervals (95% CIs) to explore the association between deterioration to high depression levels and selected risk factors. Median depression levels among CHWs in Vietnam doubled from 3 (IQR = 2-7) before COVID-19 to 6 (IQR = 3-9) on the PHQ-9 scale during the Tet holiday outbreak. The proportion with normal/minimal levels decreased from 77.1% (95% CI = 74.4-79.7) to 50.9% (95% CI = 47.7-54) (p-value < 0.001), while the proportion of CHWs with moderate, moderately severe, and severe depression levels increased 4.3, 4.5, and five-fold, respectively. Less sleep and poor sleep quality, working in unfavorable work environments, and being involved in contact tracing and the organization of quarantine for suspected cases were associated with an increased risk of deterioration to high depression levels. We found a substantial increase in overall depression levels among CHWs in Vietnam due to their COVID-19 related work and a particularly worrisome rise in CHWs suffering from severe depression. CHWs are an indispensable yet often overlooked cadre of work in many low- and middle-income countries and shoulder a heavy psychological burden during the COVID-19 pandemic. Targeted psychological support for CHWs is needed to improve their mental health and to ensure the sustainability of community-based health interventions during COVID-19 and future epidemics.


Trifluoperazine inhibits ovarian mitochondrial side-chain cleavage enzyme activity in the absence of calcium.
In a previous report we described the inhibitory effect of trifluoperazine (TFP) on steroidogenesis in avian granulosa cells. To clarify the possible site of action of TFP we measured the cholesterol side-chain cleavage enzyme (CSCC) activity in a mitochondrial preparation of granulosa cells isolated from mature and developing ovarian follicles. Using a calcium free medium, TFP inhibited CSCC in a dose related manner with an IC50 of 50 microM. Kinetic parameters (apparent Km and Vmax) obtained in the presence of TFP are indicative of uncompetitive inhibition of CSCC. Moreover, enzyme activity increased during follicular maturation while the efficacy of TFP was similar in both young and mature follicles. Because the inhibitory effects of TFP were manifest in medium from which calcium was omitted, it is suggested that the drug acts independently of the calcium-calmodulin system to suppress CSCC activity.


Fusion Image Guidance for Supra-Aortic Vessel Catheterization in Neurointerventions: A Feasibility Study.
Endovascular navigation through tortuous vessels can be complex. Tools that can optimise this access phase need to be developed. Our aim was to evaluate the feasibility of supra-aortic vessel catheterization guidance by means of live fluoroscopy fusion with MR angiography or CT angiography. Twenty-five patients underwent preinterventional diagnostic MRA, and 8 patients underwent CTA. Fusion guidance was evaluated in 35 sessions of catheterization, targeting a total of 151 supra-aortic vessels. The time for MRA/CTA segmentation and fluoroscopy with MRA/CTA coregistration was recorded. The feasibility of fusion guidance was evaluated by recording the catheterizations executed by interventional neuroradiologists according to a standard technique under fluoroscopy and conventional road-mapping independent of the fusion guidance. Precision of the fusion roadmap was evaluated by measuring (on a semiquantitative 3-point scale) the maximum offset between the position of the guidewires/catheters and the vasculature on the virtual CTA/MRA images. The targeted vessels were divided in 2 groups according to their position from the level of the aortic arch. The average time needed for segmentation and image coregistration was 7 ± 2 minutes. The MRA/CTA virtual roadmap overlaid on live fluoroscopy was considered accurate in 84.8% (128/151) of the assessed landmarks, with a higher accuracy for the group of vessels closer to the aortic arch (92.4%; OR, 4.88; 95% CI, 1.83-11.66; P = .003). Fluoroscopy with MRA/CTA fusion guidance for supra-aortic vessel interventions is feasible. Further improvements of the technique to increase accuracy at the cervical level and further studies are needed for assessing the procedural time savings and decreasing the x-ray radiation exposure.


A comparison of 6 osteoporosis risk assessment tools among postmenopausal women in Kuala Lumpur, Malaysia.
To compare and assess the performance of 6 osteoporosis risk assessment tools for screening osteoporosis in Malaysian postmenopausal women. Six osteoporosis risk assessments tools (the Simple Calculated Osteoporosis Risk Estimation [SCORE], the Osteoporosis Risk Assessment Instrument, the Age Bulk One or Never Estrogen, the body weight, the Malaysian Osteoporosis Screening Tool, and the Osteoporosis Self-Assessment Tool for Asians) were used to screen postmenopausal women who had not been previously diagnosed with osteoporosis/osteopenia. These women also underwent a dual-energy X-ray absorptiometry (DXA) scan to confirm the absence or presence of osteoporosis. A total of 164/224 participants were recruited (response rate, 73.2%), of which only 150/164 (91.5%) completed their DXA scan. Sixteen participants (10.7%) were found to have osteoporosis, whilst 65/150 (43.3%) were found to have osteopenia. Using precision-recall curves, the recall of the tools ranged from 0.50 to 1.00, whilst precision ranged from 0.04 to 0.14. The area under the curve (AUC) ranged from 0.027 to 0.161. The SCORE had the best balance between recall (1.00), precision (0.04-0.12), and AUC (0.072-0.161). We found that the SCORE had the best balance between recall, precision, and AUC among the 6 screening tools that were compared among Malaysian postmenopausal women.


Gonadotropin-releasing hormone deficiency in men: diagnosis and treatment with exogenous gonadotropin-releasing hormone.
Idiopathic hypogonadotropic hypogonadism in men is the result of absent or abnormal secretion of gonadotropin-releasing hormone, which prevents pubertal development. Isolated gonadotropin-releasing hormone deficiency is clinically and neuroendocrinologically heterogeneous, largely because of variation in the degree of gonadotropin-releasing hormone deficiency. Treatment with pulsatile gonadotropin-releasing hormone results in normal pubertal changes and virilization. Such treatment has been uniformly successful in normalizing release of gonadotropins and secretion of testosterone. Improvement in secondary sex characteristics and induction of spermatogenesis have been achieved in most patients. Eight of nine patients desiring induction of fertility were able to father a child. Use of pulsatile gonadotropin-releasing hormone presents a powerful model in which to examine regulation of gonadotropin secretion and the role of hypothalamic gonadotropin-releasing hormone in control of the male reproductive axis.


Hyperlipidemia in school children with family histories of premature coronary heart disease.
Children starting their schooling were given a questionnaire asking about the occurrence of premature (before 50 years of age in men, 55 years in women) coronary heart disease (CHD) in first degree relatives. 1,920 of 2,069 questionnaires were answered, 140 of the 7-year-old children were reported to have a first degree relative with premature CHD, 84 of these 140 families agreed to participate in our study. In 79 of the 84 families both the child and the parent at 'high risk' were tested. In the initial test 19 of 84 children had total cholesterol (TC) levels above the 95th percentile (greater than 5.35 mmol/l). In the repeat test 12 of the 19 TC tests remained abnormal and all 12 also had LDL-cholesterol (LDL-C) levels above the 95th percentile (greater than 3.40 mmol/l). None had abnormal HDL-cholesterol or triglyceride levels. Among the high risk parents, 12 of 79 had abnormal initial blood lipid tests. In the repeat test 10 parents had both TC and LDL-C levels above the 95th percentile. In five families both the child and the parent had abnormal TC and LDL-C levels. In conclusion, a considerable proportion of children and parents with family histories of premature CHD have TC and LDL-C concentrations above the 95th percentile (in the present study, about 40 individuals in 140 high-risk families, if the parent and child considered at high risk all had agreed to participate). Prevention of heart disease should begin in childhood when patterns of life-style are developed. Identification by obtained family histories as in the current study may be a method of choice.


The social contagion of prosocial behaviour: How neighbourhood blood donations influence individual donation behaviour.
Life-saving transfusions and numerous other medical treatments are enabled by a minority of people that donate blood. But why do some people repeatedly engage in such prosocial behaviour, especially when it is costly to themselves? This study examines to what extent social contagion within neighbourhoods - changing behaviour in response to the behaviour of others - affects repeated blood donation behaviour. We draw on longitudinal survey and register data from a representative sample of blood donors in the Netherlands from 2007 to 2014 (N = 15,090). Using a panel data model and an instrumental variable approach, we find that donors are positively affected by donations made by other donors living in their neighbourhood. This effect does not seem to be mediated by normative or informational social influence. Exploratory analysis further attributes this finding to social contagion within donor couples. Our study contributes to the literature on repeated blood donation behaviour, and can inform retention strategies of blood banks.


The nosological position of Fisher's syndrome (ophthalmoplegia, ataxia and areflexia).
Fisher's syndrome was studied in six patients, one of whom was an 11-year-old girl, and the nosological position of this neuro-ophthalmological disorder was reviewed. The clinical features of the ophthalmoplegia in these cases were reported as secondary to a transient inflammatory lesion in the mid-brain; this was demonstrated in one of the cases by an enhancing area on CT scan. This mid-brain localization could explain not only the classical Fisher's triad but also many variations of the syndrome. The overlap of our cases of Fisher's syndrome with so-called brain-stem encephalitis of Bickerstaff has been emphasized. Many cases of Fisher's syndrome could therefore correspond to an inflammatory process at brain-stem level with or without nerve-root involvement. Clinical and neurophysiological findings show, however, that there is peripheral damage in some cases, so that a neutral attitude needs to be maintained on the nosological position of Fisher's syndrome.


Trace heavy metals and harmful elements in roots and rhizomes of herbs: Screening level analysis and health risk assessment.
Heavy metal and harmful element contamination are frequently reported in Chinese herbal medicines (CHMs), and roots and rhizomes parts showed a higher content than other parts. To investigate the residue level and assess the potential human health risk of heavy metals and harmful elements in roots and rhizomes, 720 batches of the sample representing 20 species of herbs from different sources were collected. The content of Pb, Cd, As, Hg, and Cu in the digests was determined using ICP-MS. The chronic hazard index estimate based on non-cancer hazard quotient (HQ) was applied for potential health risk assessment of Pb, Cd, As, Hg, and Cu via consumption of CHMs. Compared with the Chinese limit standard (Chinese Pharmacopoeia Commission, 2020 edition) of Pb, Cd, As, Hg, and Cu in Ginseng Radix et Rhizoma, the exceedance percentage of Pb in total samples was 14.1%, which were generally far higher than Cd, As, Hg, and Cu. Health risk assessment results based on hazard quotient calculating showed that total HQ of Cu, Pb, As, Cd, and Hg in Pulsatillae Radix and Clematidis Radix et Rhizoma exceeded 1, with the value of 1.543 and 1.235. Besides, Arsenic had the highest HQ value (0.957) in Pulsatillae Radix . Consuming raw materials of Pulsatillae Radix and Clematidis Radix et Rhizoma may pose a potential risk and Arsenic residues in Pulsatillae Radix deserved special attention.


Hepatobiliary cystadenoma: a case report and a review of the literature.
Hepatic cystic lesions are rare; however, their management and treatment is dependent on early recognition and diagnosis. In this report, the authors discuss a 72-year-old woman who presented to their clinic for treatment of a hepatocystadenoma. The history, physical examination, and diagnostic modalities lead to surgical intervention despite an unclear diagnosis. This case illustrates an unusual hepatic lesion in which the diagnosis was not known until the time of laparotomy. However, diagnostic modalities were important in establishing the need for surgical intervention. The authors offer a pertinent review of the literature and discuss current treatment modalities.


Isomeric stability of indaziflam and major degradation products in the environment.
Understanding the isomeric behavior of active ingredients in the soil and water environment is the first and a major part of deriving an exposure assessment. Whilst a variety of approaches have been taken previously, with the new regulatory framework for the risk assessment of isomeric plant protection compounds recently published by EFSA, (European Food Safety Authority) there will in future be a more consistent approach which has been taken here. For indaziflam (IAF), the alkylazine, cross spectrum residual herbicide which has a cellulose biosynthesis inhibition mode of action, there was no published data on the isomeric degradation behavior in soil and water. The results of measuring the isomeric stability of [14C]-radiolabeled 437-IAF, the major stereoisomer of indaziflam (AE 1170437, [1R,2S,6R] configuration) during its degradation in an aerobic soil metabolism study with four EU soils, an aerobic aquatic metabolism study with two natural water/sediment test systems, as well as an aqueous photolysis study are reported. To sum up, it was shown that in the different environmental conditions under abiotic as well as biotic degradation processes, indaziflam was not subject to isomeric interconversion to diastereoisomers 435-IAF (RRR), 438-IAF (RSS), or 439-IAF (SSR). Thus, all three chiral centers of indaziflam can be considered isomerically stable. In addition, no isomeric interconversion was observed at the 1-fluoroethyl position for the major degradation products IAF-indanone and IAF-carboxylic acid to the RSS-configuration as well as IAF-diaminotriazine from the R- to the S-configuration.


A low-grade increase of serum pancreatic exocrine enzyme levels by dipeptidyl peptidase-4 inhibitor in patients with type 2 diabetes.
A potential adverse effect of dipeptidyl peptidase-4 inhibitors (DPP-4i) on the pancreas remains controversial. We evaluated the DPP-4i effects on pancreatic amylase and lipase activity in patients with type 2 diabetes. These enzymes were slightly but significantly increased, suggesting DPP-4i cause a low-grade inflammatory change in the exocrine pancreas.


Cross-Conjugated Polycatechol Organic Cathode for Aqueous Zinc-Ion Storage.
The rapid development of aqueous zinc-ion batteries poses a challenge for the exploration of cathode materials with high capacity and long cycle life. Organic materials are considered an appropriate choice owing to their structural flexibility and tunable surface chemistry. However, most organic cathode materials still have some shortcomings, such as low electrical conductivity, high cost, and limited cycling durability. Here, a facile synthesis of a novel organic composite cathode composed of cross-conjugated polycatechol (PC) combined with graphene (PC/G) is reported. The PC/G cathode is used for aqueous zinc-ion storage, wherein many hydroxy groups in the PC/G composite cathode can be converted into redox-active carbonyl groups at the initial discharge-charge. This composite cathode can deliver a high specific capacity of 355 mAh g-1 at 0.1 C and a specific capacity of 171 mAh g-1 at 10 C. Moreover, the composite cathode can retain 74.4 % of its initial capacity after 3000 discharge-charge cycles at 2 C. This coordination route to zinc ions within the PC/G composite cathode can avoid the destruction of the cathode material during discharge-charge. This organic cathode shows great promise for reversible zinc-ion storage, bringing aqueous zinc-ion batteries a step closer to future practical applications.


Myocardial infarction size and location: a comparative study of epicardial isopotential mapping, thallium-201 scintigraphy, electrocardiography and vectorcardiography.
Based on epicardial isopotential mapping (the Ep Map), which was calculated from body surface isopotential mapping (the Body Map) with Yamashita's method, using the finite element technique, we predicted the location and size of the abnormal depolarized area (the infarcted area) in 19 clinical cases of anterior and 18 cases of inferoposterior infarction. The prediction was done using Toyama's diagnostic method, previously reported. The accuracy of the prediction by the Ep Map was assessed by comparing it with findings from thallium-201 scintigraphy (SCG), electrocardiography (ECG) and vectorcardiography (VCG). In all cases of anterior infarction, the location of the abnormal depolarized areas determined on the Ep Map, which was localized at the anterior wall along the anterior intraventricular septum, agreed with the location of the abnormal findings obtained by SCG, ECG and VCG. For all inferoposterior infarction cases, the abnormal depolarized areas were localized at the posterior wall and the location also coincided with that of the abnormal findings obtained by SCG, ECG and VCG. Furthermore, we ranked and ordered the size of the abnormal depolarized areas, which were predicted by the Ep Map for both anterior and inferoposterior infarction cases. In the cases of anterior infarction, the order of the size of the abnormal depolarized area by the Ep Map was correlated to the size of the abnormal findings by SCG, as well as to the results from Selvester's QRS scoring system in ECG and to the angle of the maximum QRS vector in the horizontal plane in VCG.(ABSTRACT TRUNCATED AT 250 WORDS)


Characterization of the 5'-flanking promoter region of the rat somatostatin receptor subtype 3 gene.
We investigated the 5'-flanking promoter region of the rat somatostatin receptor subtype 3 (rSSTR3). Using a cDNA probe, genomic clones containing the 5'-flanking promoter region of the rSSTR3 gene were isolated. A sequence of 5.4 kb directly upstream from the start codon was analyzed and two introns were found in the 5' untranslated region (UTR) of the cDNA sequence. The transcriptional initiation site was determined by 5' rapid amplification of cDNA ends (RACE), primer extension and RNase protection analysis with cerebellar RNA. Two major transcriptional initiation sites were found at position 1040 (tsp1) and -856 (tsp2) relative to the translational initiation site. Like a number of other promoters of G-protein-coupled receptors, the rSSTR3 gene lacks TATA and CAAT motifs and includes G+C-rich regions. Functional analysis of the promoter region by transfecting rSSTR3 luciferase-reporter gene constructs into rat pituitary GH3 cells and HEK 293 cells indicated that a 107-bp region upstream of tsp2 was sufficient to drive transcription. Furthermore a 562-bp region at position -1304 to -1865 upstream of the ATG start codon exerted a negative regulatory effect on transcriptional activity.


Investigation of the SOS response of Escherichia coli after gamma-irradiation by means of the SOS chromotest.
The kinetics of SOS system induction in Escherichia coli PQ37 cells by gamma-irradiation has been studied by the SOS chromotest technique. It was shown that the synthesis of constitutive alkaline phosphatase is not immediately stopped in cells that suffered lethal damages from gamma-irradiation. The production of DNA damages inducing the SOS system was 0.021/Gy per genome. The SOS system was switched off approximately 200 min after gamma-irradiation. A correction is proposed to the calculation of the SOS system induction factor.


[Review on nonessential constituents of vegetables. I. Cumcumbers, melons, squashes and pumpkins, bell peppers, eggplants, peas, beans, and broad beans (author's transl)].
In this paper the known constituents of the vegetables mentioned in the title are reviewed, except for proteins, carbohydrates, triglyceride-fatty acids, and vitamins, with particular emphasis on volatiles, organic acids, phenolics, crotenoids, sterols, bitter principles, nonprotein-N-compounds.


The indirect impact of COVID-19 pandemic on limb preservation care- a retrospective analysis of trends in lower limb revascularisation.
Disruptions caused by COVID-19 pandemic have profoundly influenced the management of many conditions, especially vascular pathologies including limb preservation care. The aim of this study is to evaluate the impact of the pandemic on patients with peripheral arterial disease (PAD) focusing on lower limb revascularisation procedure volume, their indication and urgency of surgery. The Australian Vascular Audit (AVA) was used to capture data on revascularisation procedures before and after the onset of the pandemic in Victoria, Australia. Information on patient demographics, procedures performed, their indication and urgency of surgery were collected. There was a significant 22.7% increase in revascularisations for PAD during the COVID-19 pandemic, driven solely by a 31.9% increase in endovascular revascularisation procedures. Revascularisation procedures for all indications of PAD, namely claudication, rest pain and tissue loss, increased by 14.8%, 39.2% and 27.4% respectively, during the pandemic compared to pre-pandemic times. Open procedures declined by 10.2% during the pandemic. There were significant 13.9% and 62.2% increases in elective and semi-urgent revascularisations respectively during the pandemic while emergency revascularisations for PAD fell by 4.2%. There were no significant increases in toe, forefoot or below knee amputations during the pandemic compared to pre-pandemic times. This study found that the volume of revascularisation for PAD increased significantly during the pandemic indicating that patients with PAD had significant deterioration of their condition during the pandemic. This is likely multifactorial; due to disruptions to standard provision of podiatry, vascular surgery and endocrinology services to these patients, a decline in overall health and changes in health-related behaviours due to restrictions and infection control methods imposed during the pandemic. The number of elective and semi-urgent procedures also increased during the pandemic which reflects the significant deterioration of PAD patients during the pandemic. This study highlights a concerning trend of worsening PAD when routine care of these patients is disrupted. Such data should be instrumental in contingency planning and resource allocation for managing the ongoing pandemic.