Oral Citrulline Mitigates Inflammation and Jejunal Damage via the Inactivation of Neuronal Nitric Oxide Synthase and Nuclear Factor-κB in Intestinal Ischemia and Reperfusion.
Intestinal ischemia and reperfusion (I/R) is a life-threatening emergency accompanied by inflammation and organ damage. We compared the mechanisms and the effects of arginine, citrulline, and glutamine on inflammation and intestinal damage. Male Wistar rats underwent 60 minutes of superior mesenteric artery occlusion and either 3 (I/R3) or 24 (I/R24) hours of reperfusion and were orally administered vehicle, arginine, citrulline, or glutamine 15 minutes before reperfusion and at 3, 9, and 21 hours of reperfusion. I/R3 rats experienced jejunal damage and apoptosis, and I/R24 rats had liver dysfunction compared with normal rats (one-way ANOVA, P < .05). Arginine and citrulline administrations improved jejunal morphology, and citrulline and glutamine administrations alleviated the loss of jejunal mass in I/R3 rats. I/R3-increased circulating nitrate/nitrite (NOx), tumor necrosis factor-α, and interleukin-6 were significantly decreased by citrulline, glutamine and citrulline, and arginine, glutamine, and citrulline, respectively. These amino acids decreased plasma NOx and interferon-γ in I/R24, decreased jejunal neuronal nitric oxide synthase (NOS) protein in I/R3 rats, and alleviated jejunal apoptosis in I/R3 and I/R24 rats. In addition, the jejunal phosphorylated to total nuclear factor-κB (NF-κB) ratio was decreased by arginine and citrulline in I/R24 rats. Oral administration of arginine, citrulline, and glutamine may alleviate systemic inflammation, jejunal apoptosis, and neuronal NOS in intestinal I/R. Citrulline may further attenuate jejunal damage by preserving jejunal mass, partially via the inactivation of NOS and the NF-κB pathway. In conclusion, oral citrulline may have more benefits than arginine and glutamine in mitigating intestinal ischemia and reperfusion-induced adverse effects.


The clinical relevance of treating social phobia.
Social phobia is an extreme fear of being scrutinized by others in social situations that often culminates in avoidance of those situations. Studies have demonstrated marked educational, occupational and social disabilities in patients with social phobia. However, many sufferers do not seek help and are not detected when seeking medical advice for other conditions. The advent of a range of effective treatments, in particular the selective serotonin reuptake inhibitors, has substantially improved the prognosis in these sufferers, both symptomatically and in terms of quality of life.


Acute-phase proteins or tumour markers: the role of SAA, SAP, CRP and CEA as indicators of metastasis in a broad spectrum of neoplastic diseases.
Two hundred and seventy-seven patients with a broad spectrum of neoplastic diseases, including 10 classes of solid tumours and three classes of haematologic malignancies, were retrospectively surveyed, and from the same sample of plasma or serum their concentrations of serum amyloid A (SAA), serum amyloid P component (SAP), C-reactive protein (CRP), and carcinoembryonic antigen (CEA) were measured. SAA levels varied from 105 ng/ml to 105,000 ng/ml, and mean SAA levels were higher in patients with metastatic tumours than in those with limited disease (P less than 0.001). Similarly, CRP levels varied from less than 8 micrograms/ml to 328 micrograms/ml and were significantly higher in the metastatic disease category. In contrast, SAP levels varied from 32 micrograms/ml to 120 micrograms/ml and showed no difference in patients with limited or metastatic disease, although an overall slight elevation was present. CEA levels were available in 150 patients and were significantly higher in patients with advanced lung or breast cancer than in patients with limited disease. The correlation between mean SAA and CRP levels was significant (r = 0.74, P less than 0.001), suggesting that SAA originates as an acute-phase protein rather than as a tumour cell product. However, the consistent elevation of SAA in all tumour types and the more marked elevation in metastatic disease may make its measurement useful in malignancy.


Self-organization of laterally asymmetrical movements as a consequence of space-time optimization.
Laterally asymmetrical movements are ubiquitous among organisms. A bilaterally symmetrical organism cannot maneuver through a two- or three-dimensional space unless and until one side of its body leads, because the forces that cause the movements of the body are generated within the body. One question follows: are there any costs or benefits of laterally asymmetrical movements? We test whether directionally consistent laterally asymmetrical movements at different levels of organization of movements (at the individual, and not the population level) can work synergistically. We show-by means of a hypothetical system resembling a humanoid robot-that a laterally asymmetrical movement at a lower level of organization of movements can stimulate laterally asymmetrical movements that are directionally consistent at consecutive higher levels. We show-by comparing two hypothetical systems, incorporating laterally symmetrical and asymmetrical movements, respectively-that the asymmetrical system outperforms the symmetrical system by optimizing space and time and that this space-time advantage increases with the increasing complexity of the task. Together, these results suggest that laterally asymmetrical movements can self-organize as a consequence of space-time optimization.


Birth cohort effects among US-born adults born in the 1980s: foreshadowing future trends in US obesity prevalence.
Obesity prevalence stabilized in the US in the first decade of the 2000s. However, obesity prevalence may resume increasing if younger generations are more sensitive to the obesogenic environment than older generations. We estimated cohort effects for obesity prevalence among young adults born in the 1980s. Using data collected from the National Health and Nutrition Examination Survey between 1971 and 2008, we calculated obesity for respondents aged between 2 and 74 years. We used the median polish approach to estimate smoothed age and period trends; residual non-linear deviations from age and period trends were regressed on cohort indicator variables to estimate birth cohort effects. After taking into account age effects and ubiquitous secular changes, cohorts born in the 1980s had increased propensity to obesity versus those born in the late 1960s. The cohort effects were 1.18 (95% CI: 1.01, 1.07) and 1.21 (95% CI: 1.02, 1.09) for the 1979-1983 and 1984-1988 birth cohorts, respectively. The effects were especially pronounced in Black males and females but appeared absent in White males. Our results indicate a generational divergence of obesity prevalence. Even if age-specific obesity prevalence stabilizes in those born before the 1980s, age-specific prevalence may continue to rise in the 1980s cohorts, culminating in record-high obesity prevalence as this generation enters its ages of peak obesity prevalence.


All-cause mortality in the cohorts of the Spanish AIDS Research Network (RIS) compared with the general population: 1997-2010.
Combination antiretroviral therapy (cART) has produced significant changes in mortality of HIV-infected persons. Our objective was to estimate mortality rates, standardized mortality ratios and excess mortality rates of cohorts of the AIDS Research Network (RIS) (CoRIS-MD and CoRIS) compared to the general population. We analysed data of CoRIS-MD and CoRIS cohorts from 1997 to 2010. We calculated: (i) all-cause mortality rates, (ii) standardized mortality ratio (SMR) and (iii) excess mortality rates for both cohort for 100 person-years (py) of follow-up, comparing all-cause mortality with that of the general population of similar age and gender. Between 1997 and 2010, 8,214 HIV positive subjects were included, 2,453 (29.9%) in CoRIS-MD and 5,761 (70.1%) in CoRIS and 294 deaths were registered. All-cause mortality rate was 1.02 (95% CI 0.91-1.15) per 100 py, SMR was 6.8 (95% CI 5.9-7.9) and excess mortality rate was 0.8 (95% CI 0.7-0.9) per 100 py. Mortality was higher in patients with AIDS, hepatitis C virus (HCV) co-infection, and those from CoRIS-MD cohort (1997-2003). Mortality among HIV-positive persons remains higher than that of the general population of similar age and sex, with significant differences depending on the history of AIDS or HCV coinfection.


Patient perceptions of foot disability in Juvenile Idiopathic Arthritis: a comparison of the juvenile arthritis foot disability index and the Oxford ankle foot questionnaire for children.
The Juvenile Arthritis Foot Disability Index (JAFI) and the Oxford Ankle Foot Questionnaire for Children (OxAFQ-C) are two region-specific paediatric outcome tools that measure the impact on well-being in children with foot pathology. The aim of this study was to establish the level of agreement between the JAFI and the OxAFQ-C in a group of children diagnosed with Juvenile Idiopathic Arthritis (JIA). Children with JIA accessed the questionnaire via a website. The OxAFQ-C questionnaire and the JAFI questionnaire were combined into one document consisting of 42 statements with Likert-scale responses. A further question regarding duration of disease was added. On completion, the web-linked questionnaire was returned by e-mail. Thirty five participants were included. Individual domain and composite score analysis was undertaken. The JAFI participation domain was compared to the OxAFQ-C school domain and showed no significant difference between the median scores of each participant (z = -1.33, p = 0.181). The JAFI activity and the OxAFQ-C physical domains were compared and showed that a significant difference between the median scores existed (z = -4.29, p < 0.001). Agreement between the two PROMs was tested using Bland Altman Levels of Agreement based upon the percentage summed composite scores. Levels of agreement between the scores were considered to be poor based on the Bland Altman plot, despite a low mean difference in scores (mean difference = -3.88, SD of difference = 9.93, p = 0.027). Pearson correlation was undertaken to measure the relationship between the summed composite score and disease duration. No relationship was found (JAFI: r = -0.08, p = 0.672; OxAFQ-C: r = 0.037, p = 0.871). This study has shown that despite some agreement between the individual domains, overall there is poor agreement between the OxAFQ-C and the JAFI percentage summed composite scores. The study is not able to determine if one score is superior to the other but both scores could be of value when used in this population.


GD2-Targeting CAR T Cells Show Promise in H3K27M-Mutated Gliomas.
Three out of four patients treated with GD2-targeting CAR T cells showed radiographic and clinical improvement.


Symptomatic and asymptomatic interphalageal osteoarthritis: An ultrasonographic study.
To date few studies have examined whether ultrasonography can depict morphologic differences in painful and painless osteoarthritis (OA). This study describes and compares the clinical, radiographic and ultrasonographic findings of patients with both painful and painless proximal interphalgeal (PIP) and/or distal interphalgeal (DIP) OA. Patients with PIP and/or DIP OA (ACR criteria) were prospectively recruited. The clinical rheumatologist chose up to 3 painful joints and up to 3 painless symmetric joints in each patient to define 2 cohorts of OA: symptomatic (SG) and asymptomatic (ASG). A conventional postero-anterior hand x ray was performed and read by one rheumatologist following the OARSI atlas, blinded to clinical and sonographic data. Ultrasound (US) was performed by an experienced rheumatologist, blinded to both clinical and radiographic data in joints previously selected by the clinical rheumatologist. US-pathology was assessed as present or absent as defined in previous reports: osteophytes, joint space narrowing, synovitis, intra-articular power doppler signal, intra-articular bony erosion, and visualization of cartilage. Radiographic and ultrasonographic intrareader reliability test was performed. A total of 50 joints in the SG and ASG were included from 20 right handed women aged 61.85 (46-73) years with PIP and DIP OA diagnosed 6.8 (1-17) years ago. 70% SG joints and ASG were right and left sided respectively. The SG showed significantly more osteophytes, synovitis and non-visualization of joint cartilage. Intrareader radiographic and ultrasonographic agreement was excellent. This study demonstrates that painful PIP and/or DIP OA have more ultrasonographic structural changes and synovitis.


A perspective on how the Vitamin D sterol/Vitamin D receptor (VDR) conformational ensemble model can potentially be used to understand the structure-function results of A-ring modified Vitamin D sterols.
The steroid hormone 1alpha,25(OH)(2)-Vitamin D(3) (1,25D) activates both genomic and non-genomic intracellular signaling cascades. It is also well recognized that co-incubation of 1,25D with its C-1 epimer, 1beta,25D (HL), suppresses the efficiency of the non-genomic signal activated by 1,25D alone and that its C-3 epimer, 3alpha-1,25D (HJ) is nearly as potent as 1,25D in suppressing PTH secretion, believed to be propagated by 1,25D's genomic signaling. Both these sterols lack the hypercalcemic effect induced by pharmacological doses of 1,25D and have reduced VDR affinity compared to 1,25D, as measured in a steroid competition assay. Recent functional studies suggest that the VDR is required for both non-genomic and genomic signaling. Along these lines we have recently proposed a Vitamin D sterol/VDR conformational ensemble model that posits the VDR contains two distinct, yet overlapping ligand binding sites, and that the potential differential stabilities of 1,25D and HL in these two pockets can be used to explain their different non-genomic signaling properties. The overlapping region is predominantly occupied by the sterol's A-ring when it is bound to either the genomic ligand binding pocket (G-pocket), defined by X-ray crystallography, or the alternative ligand binding pocket (A-pocket), discovered using in silico techniques (directed docking). Therefore, to gain further insight into the potential application of this model we docked the other A-ring diastereomer [(1beta,3alpha)=HH] of 1,25D and its 1- and 3-deoxy forms (25D and CF, respectively) to the A- and G-pockets to assess their potential stabilities in the pockets, relative to 1,25D. The models were then used to provide putative mechanistic arguments for their known structure-function experimental results. This model may provide new insights into how Vitamin D sterols that uncouple the unwanted hypercalcemic effect from attractive growth inhibitory/differentiation properties can do so by differentially stabilizing different subpopulations of VDR conformational ensemble members.


Myocardial infarction due to left main coronary artery total occlusion: A unique electrocardiographic presentation.
Left main coronary artery (LMCA) total occlusion typically presents as anterolateral ST-segment myocardial infarction with or without right bundle branch block with left anterior fascicular block, and ST-segment elevation in aVR. On the contrary to the previously described electrocardiographic pattern we describe a distinct electrocardiographic presentation in a patient with total LMCA occlusion characterized by the presence of complete LBBB co-existing with upsloping ST-segment depression in precordial leads leading to symmetrical, tall, positive T waves, the so called de Winter's sign.


Laparoscopic Nissen fundoplication is less expensive than open Belsey Mark IV.
Laparoscopic Nissen fundoplication is a relatively new technique used to treat gastroesophageal reflux disease (GERD). The purpose of this study was to compare the cost to the patient and insurer of a laparoscopic Nissen fundoplication (LN) to an open Belsey Mark IV (B4), the previous standard operation for GERD at Emory University Hospital. A retrospective review of 20 consecutive patients undergoing LN or B4 for GERD was performed. Patients were well matched for age, severity of disease, and comorbid illness. The data were analyzed using an unpaired Student's t-test or Wilcoxon signed rank analysis. The results are as follows (mean +/- SD): [table: see text] We conclude that the charges for laparoscopic Nissen fundoplication are significantly less than the charges for Belsey Mark IV. The majority of the savings resulted from a shortened hospital stay.


Aerobic Mercury-resistant bacteria alter Mercury speciation and retention in the Tagus Estuary (Portugal).
Aerobic mercury-resistant bacteria were isolated from the sediments of two highly mercury-polluted areas of the Tagus Estuary (Barreiro and Cala do Norte) and one natural reserve area (Alcochete) in order to test their capacity to transform mercury. Bacterial species were identified using 16S rRNA amplification and sequencing techniques and the results indicate the prevalence of Bacillus sp. Resistance patterns to mercurial compounds were established by the determination of minimal inhibitory concentrations. Representative Hg-resistant bacteria were further tested for transformation pathways (reduction, volatilization and methylation) in cultures containing mercury chloride. Bacterial Hg-methylation was carried out by Vibrio fluvialis, Bacillus megaterium and Serratia marcescens that transformed 2-8% of total mercury into methylmercury in 48h. In addition, most of the HgR bacterial isolates showed Hg(2+)-reduction andHg(0)-volatilization resulting 6-50% mercury loss from the culture media. In summary, the results obtained under controlled laboratory conditions indicate that aerobic Hg-resistant bacteria from the Tagus Estuary significantly affect both the methylation and reduction of mercury and may have a dual face by providing a pathway for pollution dispersion while forming methylmercury, which is highly toxic for living organisms.


The relationship between sperm quality in cool-shipped semen and embryo recovery rate in horses.
The relationship between the quality of cool-shipped stallion semen and fertility has not been adequately described. This study evaluated sperm quality of cool-shipped semen from 459 ejaculates (N = 130 stallions) that were used for insemination of 196 embryo donor mares (n = 496 estrous cycles). Embryo recovery rate (ERR; %) increased, as all sperm measures (e.g., motility, viability, DNA quality, morphology, concentration, and total number) increased. Threshold values are reported for each sperm quality measure (e.g., total sperm motility ≥ 65%) that separate two ERR groups (e.g., average: ∼50% ERR; high: ∼65% ERR).


Ability of detecting and willingness to share fake news.
By conducting large-scale surveys in Germany and the United Kingdom, we investigate the individual-level determinants of the ability to detect fake news and the inclination to share it. We distinguish between deliberate and accidental sharing of fake news. We document that accidental sharing is much more common than deliberate sharing. Furthermore, our results indicate that older, male, high-income, and politically left-leaning respondents better detect fake news. We also find that accidental sharing decreases with age and is more prevalent among right-leaning respondents. Deliberate sharing of fake news is more prevalent among younger respondents in the United Kingdom. Finally, our results imply that respondents have a good assessment of their ability to detect fake news: those we identified as accidental sharers were also more likely to have admitted to having shared fake news.


Motion cues from the background influence associative color learning of honey bees in a virtual-reality scenario.
Honey bees exhibit remarkable visual learning capacities, which can be studied using virtual reality (VR) landscapes in laboratory conditions. Existing VR environments for bees are imperfect as they provide either open-loop conditions or 2D displays. Here we achieved a true 3D environment in which walking bees learned to discriminate a rewarded from a punished virtual stimulus based on color differences. We included ventral or frontal background cues, which were also subjected to 3D updating based on the bee movements. We thus studied if and how the presence of such motion cues affected visual discrimination in our VR landscape. Our results showed that the presence of frontal, and to a lesser extent, of ventral background motion cues impaired the bees' performance. Whenever these cues were suppressed, color discrimination learning became possible. We analyzed the specific contribution of foreground and background cues and discussed the role of attentional interference and differences in stimulus salience in the VR environment to account for these results. Overall, we show how background and target cues may interact at the perceptual level and influence associative learning in bees. In addition, we identify issues that may affect decision-making in VR landscapes, which require specific control by experimenters.


Mechanism of Sijunzi Decoction in the treatment of colorectal cancer based on network pharmacology and experimental validation.
Sijunzi Decoction(SJZD), as a famous classical prescription for the treatment of colorectal cancer(CRC) in the traditional Chinese medicine (TCM), has achieved good curative effects in clinical practice. However, its specific ingredients and molecular mechanisms is still unclear. To analyze the effective ingredients and molecular mechanisms of SJZD in the treatment of CRC through network pharmacology technology and experimental validation. First, the TCM Systems Pharmacology database and analysis platform database were searched to screen the effective chemical components of SJZD. Swiss Target Prediction was used to predict corresponding potential target genes of compounds. After that, we constructed a components and corresponding target network by Cytoscape. Simultaneously, 5 disease databases were used to search and filter CRC targets, and then we constructed a drug-disease target protein-protein interaction (PPI) network. Cytoscape 3.7 was used for visualization and cluster analysis, and Metascape database was used for GO and KEGG enrichment analysis. We drew the main pathway-target network diagram. Autodock vina1.5.6 was applied to molecular docking for the main compounds and target proteins. Subsequently, the potential mechanism of SJZD on colon cancer predicted by network pharmacological analysis was experimentally studied and verified in vivo and in vitro. 144 effective active chemical components, 897 potential targets, and 2584 CRC target genes were screened out. The number of common targets between the SJZD and CRC was 414.3250 GO biological process items and 186 KEGG signal pathways were obtained after analysis. The main compounds and the target protein had a good binding ability in molecular docking. The results of cell and animal experiments showed that SJZD could promote apoptosis and autophagy of CRC cells through PI3K/Akt/mTOR pathway. SJZD can treat CRC through multiple components, multiple targets and multiple pathways. We initially revealed the effective components and molecular mechanisms of SJZD in the treatment of CRC, and we used molecular docking and experiment for preliminary verification.


Associations between empirically derived dietary patterns and oxidative stress and inflammation in adults with primary hypothyroidism: a case-control study.
Primary hypothyroidism is a common endocrine disorder caused by impaired production of thyroid hormones. Recent studies have shown that dietary habits, oxidative stress, and inflammation may play roles in thyroid hypofunction. Thus, the present article aimed to determine the relationship between major dietary patterns and oxidative stress and inflammation in primary hypothyroid patients and healthy people in Iranian adults. This matched case-control study was conducted on 200 participants (100 cases and 100 controls). The presence of primary hypothyroidism was determined by endocrinologists based on American Thyroid Association (ATA) criteria. Dietary intake was assessed using a validated 168-item, semi-quantitative food frequency questionnaire (FFQ). The principal component analysis (PCA) method was used to derive major dietary patterns. Statistical analysis was performed using logistic regression analysis, and the findings were reported using odds ratios (ORs) with 95% CIs. We identified 2 major dietary patterns (i.e., healthy and Western dietary patterns). After adjusting for confounding variables, participants in the highest tertile of the healthy eating pattern had lower odds of primary hypothyroidism. Also, there was a significant relationship between total antioxidant capacity (TAC) levels and thyroid hypofunction; however, no significant correlation was seen between the Western dietary pattern and malondialdehyde (MDA) and C-reactive protein (CRP) with hypothyroidism. There were statistically direct associations between healthy dietary patterns (loaded with vegetables, nuts and seeds, fruits, dried fruits, olives, garlic, black pepper, starchy vegetables, low-fat dairy, and legumes) and increased TAC levels with a decreased risk of thyroid hypofunction. However, Western dietary patterns and MDA and CRP levels did not associate with an underactive thyroid.


Focal adhesion kinase pp125FAK is associated with both intercellular junctions and matrix adhesion sites in vivo.
Previous studies have characterized pp125FAK as a focal adhesion (FA)-associated non-receptor tyrosine kinase. However, there are few data available on the expression and localization of this kinase in tissues. In this study we show that in human tissues the highest expression of pp125FAK is found in some developing epithelia, where pp125FAK is associated with either intercellular junctions or with sites of adhesion to the basement membrane, whereas the same adult tissues show only a faint reactivity. Connective tissue cells do not show any reactivity for pp125FAK in vivo, but developing arterial smooth muscle expresses pp125FAK at high levels. The expression pattern in malignant tissues is variable, but most carcinomas do not express this kinase. In primary cultures of human amnion epithelial cells pp125FAK first becomes associated with the polarized adhesion lamellae, but is subsequently translocated to the forming adherens junctions (AJs). Later upon culturing pp125FAK becomes associated with prominent FAs, as in cultured cell lines. Taken together, our results suggest that the association of pp125FAK with FAs in cultured cells is principally due to a process of adaptation, whereas in vivo pp125FAK mainly functions as a regulatory component of intercellular AJs and cell-matrix adhesions of developing epithelia and also in developing arterial smooth muscle.


Diabetic microvascular complications associated with myocardial repolarization heterogeneity evaluated by Tp-e interval and Tp-e/QTc ratio.
The heterogeneity in myocardial repolarization increases the risk of ventricular arrhythmias and sudden death in patients with diabetes mellitus (DM). The Tp-e interval and Tp-e/QTc ratio are found to be useful in the prediction of ventricular arrhythmias. In this study, we aimed to investigate the Tp-e interval and Tp-e/QTc ratio in diabetic patients with and without microvascular complications. This cross-sectional observational study included patients with type 2 DM who presented to the endocrinology outpatient clinic. Diabetic microvascular complications were evaluated. The Tp-e interval, Tp-e/QT ratio, and Tp-e/QTc ratio were also calculated. A total of 240 patients with type 2 DM (148 patients had microvascular complications) were included in the study. Diabetic neuropathy rate was 30.4%, diabetic nephropathy rate was 38.4%, and diabetic retinopathy rate was 21.7%. Upon comparing patients according to Tp-e/QTc ratio, the median Tp-e/QTc interval of the group of patients with complications was 0.21 (0.19-0.23) and the median Tp-e/QTc ratio of the group of patients without complications was 0.19 (0.18-0.20) (p < 0.001). When patients were grouped according to the presence and severity of retinopathy, the Tp-e/QTc ratio was more prolonged in the proliferative retinopathy group [0.27 (0.23-0.30)] than the non-proliferative retinopathy group [0.20 (0.19-0.22), p < 0.001]. When patients were grouped according to the presence and severity of nephropathy, the Tp-e/QTc ratio was more prolonged in the macroalbuminuria and microalbuminuria group than the normoalbuminuric group [0.25 (0.21-0.30), 0.23 (0.19-0.24), and 0.19 (0.20-0.22), respectively, p = 0.002]. Our study is the first to demonstrate the association of the Tp-e interval and Tp-e/QTc ratio with the presence and severity of microvascular complications in patients with type 2 DM.


A form of stomatitis induced by excessive peppermint consumption.
This paper reports on a form of stomatitis and glossitis associated with extremely prominent circumvalate papillae in two patients who consumed excessive amounts of mint-flavoured sweets.


The squeaky wheel gets the grease: Recipients' responses influence children's costly third-party punishment of unfairness.
Third-party punishment promotes cooperation by deterring opportunistic behaviors. Even children are willing to pay a cost to implement third-party punishment of unfair behavior. Whether in judicial practice or in daily third-party punishment, people take recipients' feelings into account out of restorative motives. Restorative motives pay attention to both the offenders and the victims and are committed to best repairing harm. This work examined whether children adopt restorative motives by considering recipients' responses when punishing unfair dividers. Participants (N = 128) were 6-, 8-, and 10-year-old Chinese children. Children were shown allocations proposed among a divider and a recipient with response (positive vs. negative) or without response and were asked to accept or pay a cost to reject the allocation. Two experiments indicated that costly third-party punishment increased with age. Furthermore, children took recipients' responses into consideration, with negative responses prompting children to punish more. These findings show that children adopted a restorative view when implementing costly third-party punishment.


Comparative biochemistry of alpha-glucan-utilization in Pseudomonas amyloderamosa and Pseudomonas saccharophila: physiological significance of variations in the pathway.
Growth patterns on and utilization of various alpha-glucans were investigated in Pseudomonas amyloderamosa and P. saccharophila. Maltose, maltodextrins (average chain length 7 glycosyl units) and glycogen supported excellent growth of both organisms and were extensively metabolized, although glycogen utilization in P. saccharophila was preceded by a prolonged lag phase. P. amyloderamosa produced limited growth on amylopectin and the carbohydrate was only partly degraded. It seemed likely that many of the unit chains liberated from amylopectin had a length exceeding the substrate range accepted by the maltodextrin permease (transport) system. A correlation was established between the pH of the medium and the utilization of glycogen and amylopectin for growth in P. amyloderamosa. The carbohydrates were at least partly utilizable at pH 6.0, whereas they could not support any growth at pH 6.5. Most likely, the lack of growth at the higher pH reflected the low activity of isolamylase at this pH. The enzyme patterns of maltodextrin catabolism in the two bacteria were established. Intracellularly, maltodextrin phosphorylase and 4-alpha-glucanotransferase occurred in both. Degradation of extracellular alpha-glucans was mediated by a mainly intracellular isoamylase in P. amyloderamosa, whereas P. saccharophila possessed an extracellular alpha-amylase and a firmly cell-bound pullulanase.


In Vivo NMR Studies of the Brain with Hereditary or Acquired Metabolic Disorders.
Metabolic disorders, whether hereditary or acquired, affect the brain, and abnormalities of the brain are related to cellular integrity; particularly in regard to neurons and astrocytes as well as interactions between them. Metabolic disturbances lead to alterations in cellular function as well as microscopic and macroscopic structural changes in the brain with diabetes, the most typical example of metabolic disorders, and a number of hereditary metabolic disorders. Alternatively, cellular dysfunction and degeneration of the brain lead to metabolic disturbances in hereditary neurological disorders with neurodegeneration. Nuclear magnetic resonance (NMR) techniques allow us to assess a range of pathophysiological changes of the brain in vivo. For example, magnetic resonance spectroscopy detects alterations in brain metabolism and energetics. Physiological magnetic resonance imaging (MRI) detects accompanying changes in cerebral blood flow related to neurovascular coupling. Diffusion and T1/T2-weighted MRI detect microscopic and macroscopic changes of the brain structure. This review summarizes current NMR findings of functional, physiological and biochemical alterations within a number of hereditary and acquired metabolic disorders in both animal models and humans. The global view of the impact of these metabolic disorders on the brain may be useful in identifying the unique and/or general patterns of abnormalities in the living brain related to the pathophysiology of the diseases, and identifying future fields of inquiry.


Metabolic switching in the sugar phosphotransferase system of Escherichia coli.
Bacteria grown in a mixture of multiple sugars will first metabolize a preferred sugar until it is nearly depleted, only then turning to other carbon sources in the medium. This sharp switching of metabolic preference is characteristic of systems that optimize fitness. Here we consider the mechanism by which switching can occur in the Escherichia coli phosphotransferase system (PTS), which regulates the uptake and metabolism of several sugars. Using a model combining the description of fast biochemical processes and slower genetic regulation, we derive metabolic phase diagrams for the uptake of two PTS sugars, indicating regions of distinct sugar preference as a function of external sugar concentrations. We then propose a classification of bacterial phenotypes based on the topology of the metabolic phase diagram, and enumerate the possible topologically distinct phenotypes that can be achieved through mutations of the PTS. This procedure reveals that there is only one nontrivial switching phenotype that is insensitive to large changes in biochemical parameters. This phenotype exhibits diauxic growth, a manifestation of the winner-take-all dynamics enforced by PTS architecture. Winner-take-all behavior is implemented by the induction of sugar-specific operons, combined with competition between sugars for limited phosphoryl flux. We propose that flux-limited competition could be a common mechanism for introducing repressive interactions in cellular networks, and we argue that switching behavior similar to that described here should occur generically in systems that implement such a mechanism.


Methods of molecular modelling of protein-protein interactions.
This article reviews briefly theoretical methods attempting to predict the structure of protein aggregates from the structural features of their subunits. The authors discuss the problems of the solvent effect and the formation of protein structure. The existing methods of quaternary structure prediction are presented and an attempt at their classification is made at the end of this review.


Are angiotensin converting enzyme inhibitors beneficial in patients with aortic stenosis?
Angiotensin converting enzyme (ACE) inhibitors may become an accepted form of treatment for aortic stenosis in the future.


Beyond "the men of steel". The origins and significance of house staff training stress.
Stress is a common and significant component of house staff training. It has a dual capacity to support and hinder the trainee's education and well-being. However, there has been infrequent attention to the purpose and significance of training stress in the medical literature. The myths and traditions of medicine that foster sayings such as "in the days of the giants" or "the men of steel" do not sufficiently explain the dynamics of house staff stress. This article examines the origins, effects, and meaning of house officer stress. Stress seems to originate from as well as influence: the psychology of physicians, patient care, hospital economics, and the relationship between trainees and educators. Adaptations to stress acquired in training influence the house officer's future professional and personal well-being. Evaluation of training stress can help clarify related issues such as physician impairment and mentoring in medical education.


Genome-wide DNA methylation status of Mongolians exhibits signs of cellular stress response related to their nomadic lifestyle.
Epigenetics is crucial for connecting environmental stresses with physiological responses in humans. Mongolia, where nomadic livestock pastoralism has been the primal livelihood, has a higher prevalence of various chronic diseases than the surrounding East Asian regions, which are more suitable for crop farming. The genes related to dietary stress and pathogenesis of related disorders may have varying epigenetic statuses among the human populations with diverse dietary cultures. Hence, to understand such epigenetic differences, we conducted a comparative analysis of genome-wide DNA methylation of Mongolians and crop-farming East Asians. Genome-wide DNA methylation status of peripheral blood cells (PBCs) from 23 Mongolian adults and 24 Thai adults was determined using the Infinium Human Methylation 450K arrays and analyzed in combination with previously published 450K data of 20 Japanese and 8 Chinese adults. CpG sites/regions differentially methylated between Mongolians and crop-farming East Asians were detected using a linear model adjusted for sex, age, ethnicity, and immune cell heterogeneity on RnBeads software. Of the quality-controlled 389,454 autosomal CpG sites, 223 CpG sites were significantly differentially methylated among Mongolians and the four crop farming East Asian populations (false discovery rate < 0.05). Analyses focused on gene promoter regions revealed that PM20D1 (peptidase M20 domain containing 1), which is involved in mitochondrial uncoupling and various processes, including cellular protection from reactive oxygen species (ROS) and thermogenesis, was the top differentially methylated gene. Moreover, gene ontology enrichment analysis revealed that biological processes related to ROS metabolism were overrepresented among the top 1% differentially methylated genes. The promoter regions of these genes were generally hypermethylated in Mongolians, suggesting that the metabolic pathway detoxifying ROS might be globally suppressed in Mongolians, resulting in the high susceptibility of this population to various chronic diseases. This study showed a significantly diverse DNA methylation status among Mongolians and crop-farming East Asians. Further, we found an association between the differentially methylated genes and various metabolic and neurodegenerative diseases. Knowledge of the epigenetic regulators might help in proper understanding, treatment, and control of such disorders, and physiological adaptation in the future.


Ca2+ in contractile processes.
The concept of Ca2+ regulation, first discovered and developed in muscle research, is historically surveyed. Ca2+ regulation mechanisms in actomyosin-dependent contractile processes are compared, emphasis being placed on the great diversity. The mode of action of Ca2+ is discussed with the examples of troponin and calmodulin, the most differentiated and conservative Ca2+-receptor proteins, respectively.


Sevoflurane pretreatment inhibits endotoxin-induced shock in rats.
We examined the effects of sevoflurane pretreatment on mortality and inflammatory responses during endotoxin-induced shock. Rats were allocated randomly to 1 of 4 groups (n = 12 per group): an endotoxemia group, receiving IV Escherichia coli endotoxin (15 mg/kg over 2 min); a saline control group, receiving 0.9% saline (1.0 mL/kg); a sevoflurane-only group, receiving 2.4% sevoflurane for 30 min immediately before injection of 0.9% saline; and a sevoflurane pretreatment group, receiving 2.4% sevoflurane for 30 min immediately before injection of endotoxin. Hemodynamic variables, arterial blood gases, and plasma concentrations of tumor necrosis factor-alpha and interleukin-6 were measured. The 8-h mortality rate was determined. Systolic arterial blood pressure and acid-base balance improved with sevoflurane pretreatment before induction of endotoxemia. Mortality rates 8 h after endotoxin injection were 83%, 8%, 0%, and 25% for the endotoxemia, saline control, sevoflurane-only, and sevoflurane pretreatment groups, respectively. Plasma cytokine concentrations were significantly larger in the endotoxemia group than in the other groups. Sevoflurane pretreatment inhibited inflammatory responses and decreased mortality in rats exposed to endotoxin. Sevoflurane pretreatment decreased mortality rate, severity of hypotension, and acidosis, and inhibited cytokine responses in rats injected with endotoxin, suggesting that sevoflurane may be an anesthetic of choice in endotoxemic states.


Toddler's diarrhoea: individual variation with environmental change.
Growing evidence suggests that environmental influences are relevant to the aetiology, maintenance and treatment of the common complaint of toddler's diarrhoea. Two presented cases demonstrate systematic fluctuations in frequency of diarrhoea by individual subjects, concurrent with changes of environment.


The relationship among androgens, insulin resistance and ghrelin polymorphisms in post-adolescent male patients with severe acne vulgaris.
Ghrelin has anti-inflammatory and immunomodulatory activities. Data about the role of ghrelin and ghrelin polymorphisms in the development of acne vulgaris in post-adolescent male patients are limited. To evaluate the role of serum androgens, insulin resistance, ghrelin and ghrelin polymorphisms in severe acne vulgaris. Thirty-five post-adolescent male patients with a mean age of 28.0 ±5.4 years and 33 age-and BMI-matched controls were enrolled. Serum androgens, lipids, insulin sensitivity parameters and ghrelin levels were determined. The PCR method was used for GHRL polymorphisms (rs27647, rs696217 and rs34911341 genotypes). Patients had similar anthropometric measures to controls, except a significantly higher WHR in patients (0.92 ±0.06 vs. 0.86 ±0.08, p < 0.05). Also, FPG, HOMA-IR values, lipid profile and serum androgen levels were similar. Interestingly, patients had significantly lower ghrelin levels than controls (4.5 ±5.8 vs. 101.2 ±86.5 pg/ml, p < 0.001). The frequencies of rs696217 and rs34911341 genotypes were similar whereas the distribution of rs27647 alleles was significantly different between the groups (p < 0.05). GA and GG genotypes of GHRL rs27647 polymorphism indicated an increased risk of developing acne vulgaris (OR = 11.156, 95% CI: 2.864-43.464, OR = 5.312, 95% CI: 1.269-22.244, respectively; p < 0.05). Patients with rs27647-AA polymorphism had significantly lower GAGS scores than other groups (AA genotype 6.7 ±14.1 vs. GA genotype 24.6 ±15.7 and GG genotype 19.4 ±17.9, p < 0.001). None of the polymorphisms had a significant effect on metabolic parameters, insulin sensitivity and serum ghrelin levels. Decreased ghrelin levels and GA and GG genotypes of GHRL gene rs27647 polymorphism may have a role in the pathogenesis of acne vulgaris.


NMR studies on fully hydrated membrane proteins, with emphasis on bacteriorhodopsin as a typical and prototype membrane protein.
The 3D structures or dynamic feature of fully hydrated membrane proteins are very important at ambient temperature, in relation to understanding their biological activities, although their data, especially from the flexible portions such as surface regions, are unavailable from X-ray diffraction or cryoelectron microscope at low temperature. In contrast, high-resolution solid-state NMR spectroscopy has proved to be a very convenient alternative means to be able to reveal their dynamic structures. To clarify this problem, we describe here how we are able to reveal such structures and dynamic features, based on intrinsic probes from high-resolution solid-state NMR studies on bacteriorhodopsin (bR) as a typical membrane protein in 2D crystal, regenerated preparation in lipid bilayer and detergents. It turned out that their dynamic features are substantially altered upon their environments where bR is present. We further review NMR applications to study structure and dynamics of a variety of membrane proteins, including sensory rhodopsin, rhodopsin, photoreaction centers, diacylglycerol kinases, etc.


Assessing Hepatitis C Burden and Treatment Effectiveness through the British Columbia Hepatitis Testers Cohort (BC-HTC): Design and Characteristics of Linked and Unlinked Participants.
The British Columbia (BC) Hepatitis Testers Cohort (BC-HTC) was established to assess and monitor hepatitis C (HCV) epidemiology, cost of illness and treatment effectiveness in BC, Canada. In this paper, we describe the cohort construction, data linkage process, linkage yields, and comparison of the characteristics of linked and unlinked individuals. The BC-HTC includes all individuals tested for HCV and/or HIV or reported as a case of HCV, hepatitis B (HBV), HIV or active tuberculosis (TB) in BC linked with the provincial health insurance client roster, medical visits, hospitalizations, drug prescriptions, the cancer registry and mortality data using unique personal health numbers. The cohort includes data since inception (1990/1992) of each database until 2012/2013 with plans for annual updates. We computed linkage rates by year and compared the characteristics of linked and unlinked individuals. Of 2,656,323 unique individuals available in the laboratory and surveillance data, 1,427,917(54%) were included in the final linked cohort, including about 1.15 million tested for HCV and about 1.02 million tested for HIV. The linkage rate was 86% for HCV tests, 89% for HCV cases, 95% for active TB cases, 48% for HIV tests and 36% for HIV cases. Linkage rates increased from 40% for HCV negatives and 70% for HCV positives in 1992 to ~90% after 2005. Linkage rates were lower for males, younger age at testing, and those with unknown residence location. Linkage rates for HCV testers co-infected with HIV, HBV or TB were very high (90-100%). Linkage rates increased over time related to improvements in completeness of identifiers in laboratory, surveillance, and registry databases. Linkage rates were higher for HCV than HIV testers, those testing positive, older individuals, and females. Data from the cohort provide essential information to support the development of prevention, care and treatment initiatives for those infected with HCV.


Regulation of the choline transport system in superfused microcarrier cultures of BeWo cells.
BeWo choriocarcinoma cells were cultured onto solid microcarrier beads, packed into syringe barrels and superfused. The unidirectional choline uptake across the microvillous membrane of the cells was measured by a rapid single-circulation paired-tracer dilution procedure using methyl[3H]choline with D-[14C]mannitol as the extracellular reference molecule. Choline influx was saturable with a K(t) of 214+/-15 microM and a V(max) of 45.29+/-0.94 nmol/min/mg of cell protein. Uptake of labelled choline was partially inhibited by nicotine, strongly inhibited by hemicolinium-3, and was reduced by about 50 per cent in sodium-free perfusates. A range of agents was added to the stirrer flasks 24 h prior to the experiments to determine if intracellular or extracellular levels of choline or its metabolic product, acetylcholine, regulated choline uptake. Pre-incubation with 2 mM choline reduced the choline maximal uptake by half, while pre-incubation with 100 microM alpha-NETA [2-(alpha-naphthoyl)ethyltrimethyl-ammonium] reduced the influx by 77 per cent. Choline influx was also reduced to about half in the presence of 100 microM vesamicol, bethanecol or neostigmine. It is concluded that BeWo cells possess a choline transporter similar to that described in isolated cytotrophoblasts and syncytiotrophoblast microvillous membrane preparations, and that uptake appeared to be regulated by both intracellular and extracellular concentrations of choline and acetylcholine. Therefore, these cells provide a novel model for studying the role of acetylcholine in human placenta.


Transthoracic versus transhiatal resection for esophageal adenocarcinoma of the lower esophagus: A value-based comparison.
Our objective was to compare clinical outcomes, costs, and resource use based on operative approach, transthoracic (TT) or transhiatal (TH), for resection of esophageal cancer. This cohort analysis utilized the Surveillance, Epidemiology, and End Results--Medicare linked data from 2002 to 2009. Only adenocarcinomas of the lower esophagus were examined to minimize confounding. Medicare data was used to determine episode of care costs and resource use. Propensity score matching was used to control for identified confounders. Kaplan-Meier method and Cox-proportional hazard modeling were used to compare long-term survival. 537 TT and 405 TH resections were identified. TT and TH esophagectomy had similar complication rates (46.7% vs. 50.8%), operative mortality (7.9% vs 7.1%), and 90 days readmission rates (30.5% vs. 32.5%). However, TH was associated with shorter length of stay (11.5 vs. 13.0 days, P = 0.006) and nearly $1,000 lower cost of initial hospitalization (P = 0.03). No difference in 5-year survival was identified (33.5% vs. 36%, P = 0.75). TH esophagectomy was associated with lower costs and shorter length of stay in an elderly Medicare population, with similar clinical outcomes to TT. The TH approach to esophagectomy for distal esophageal adenocarcinoma may, therefore, provide greater value (quality/cost).


Evolutionary and functional analysis of the key pluripotency factor Oct4 and its family proteins.
Oct4 is one of the key pluripotent factors essential for embryonic stem cells and induced pluripotent stem (iPS) cells. Oct4 belongs to the POU domain family, which contains multiples genes with various important functions. Although the function of Oct4 has been extensively studied, detailed comparison of Oct4 with other POU family genes and their evolutionary analysis are still lacking. Here, we systematically identified POU family genes from lower to higher animal species. We observed an expansion of POU family genes in vertebrates, with an additional increment in mammalian genomes. We analyzed the phylogenetic relationship, tissue specific expression profiles and regulatory networks of POU family genes of the human genome, and predicted the putative binding microRNAs of human POU family genes. These results provide the first comprehensive evolutionary and comparative analysis of POU family genes, which will help to better understand the relationships among POU family genes and shed light on their future functional studies.


Gait biomechanics and hip muscular strength in patients with patellofemoral osteoarthritis.
A significant number of patients with patellofemoral osteoarthritis (PFOA) have described a history of patellofemoral pain syndrome (PFPS). This leads to speculation that the underpinning mechanical causes of PFPS and PFOA may be similar. Although alterations in gait biomechanics and hip strength have been reported in PFPS, this relationship has not yet been explored in PFOA. Therefore the purpose of this study was compare gait biomechanics and hip muscular strength between PFOA patients and a healthy control group. Fifteen patients with symptomatic, radiographic PFOA and 15 controls participated. All patients underwent a walking gait analysis and maximal hip strength testing. Biomechanical variables of interest included the peak angular values of contra-lateral pelvic drop, hip adduction and hip internal rotation during the stance phase. Hip abduction and external rotation strength were assessed using maximal voluntary isometric contractions. The PFOA group demonstrated significantly lower hip abduction strength compared to controls but no difference in hip external rotation strength. There were no statistical differences between the PFOA and control groups for contra-lateral pelvic drop, hip adduction and hip internal rotation angles during walking. Despite patients with PFOA exhibiting weaker hip abductor muscle strength compared to their healthy counterparts they did not demonstrate alterations in pelvis or hip biomechanics during gait. These preliminary data suggests that weaker hip abductor strength does not result in biomechanical alterations during gait in this population.


[Supracondylar fracture of the humerus in children with concomitant fracture of the ipsilateral forearm].
The mode of treatment used in 6 cases of combined supracondylar fracture of the humerus and ipsilateral forearm fracture is presented. Results were rated good, fair and poor according to both functional and radiological assessments. Three cases were good and 3 fair. One stage reduction of both fractures with plaster of Paris immobilization or olecranon traction has been performed. The results achieved are corresponding with those presented in the bibliography.


Tongqiao Huoxue Decoction ameliorates learning and memory defects in rats with vascular dementia by up-regulating the Ca(2+)-CaMKII-CREB pathway.
The present study was aimed at determining the effects of Tongqiao Huoxue Decoction (TQHXD) on the Ca(2+)-CaMKII-CREB pathway and the memory and learning capacities of rats with vascular dementia (VD). The rat VD model was established by using an improved bilateral carotid artery ligation method. The Morris water maze experiment was used to evaluate the ethology of the VD rats following treatments with TQHXD at 3.01, 6.02, and 12.04 g·kg(-1) per day for 31 days. At the end of experiment, the hippocampus were harvested and analyzed. Western blotting and RT-PCR were used to measure the expression levels of calmodulin-binding protein kinase II(CaMKII), protein kinase A(PKA), cAMP-response element binding protein(CREB), and three N-methyl-D-aspartic acid receptor subunits (NR1, NR2A, and NR2B). Our results revealed that TQHXD could alleviate the loss of learning abilities and increase the memory capacity (P < 0.05 and P < 0.01 vs the model group, respectively). The treatment with 6.02 and 12.04 g·kg(-1) of TQHXD significantly up-regulated the Ca(2+)-CaMKII-CREB pathway in the hippocampus. In conclusion, TQHXD showed therapeutic effects on a bilateral carotid artery ligation-induced vascular dementia model, through the up-regulation of calcium signalling pathways.


Prevalence of Diabetes in an Urban Hospital Emergency Room Serving Predominantly Indigenous Population.
The purpose of this study was to examine the rate of diabetes and pre-diabetes in previously undiagnosed individuals who came to the Detroit Receiving Hospital-Ambulatory Rapid Center (DRH-ARC), which is part of the emergency room. This region has a high minority population with over 83% being African-Americans (AAs). Diabetes screening is especially important for this population because AAs are more prone to develop complications. Free diabetes screening was done for all patients coming to the walk in unit of the DRH-ARC. This program was supported by the "Healthy Detroit-Diabetes Initiative". The initiative was developed by the Detroit Receiving Hospital and Wayne State University Physicians Group (WSUPG) administration. A total of 15,971 patients, who did not have a history of diabetes, consented for screening during the period of March 2010 through March 2014. A total of 6,149 (38.5%) patients were found to have HbAlc values in the range of pre-diabetes or diabetes. The prevalence of diabetes increased with age in both men and women. The data showed high prevalence of undiagnosed pre-diabetes and diabetes in this population approaching 31% and 8%, respectively. Among patients with elevated blood pressure 41.2% had abnormal HbAlc values. In contrast, 32% of patients with normal blood pressure had abnormal HbAlc values. Continued screening of population at risk for diabetes is essential. Public health awareness programs, such as the Healthy Detroit-Diabetes Initiative should be initiated in similar areas where minority populations are prevalent.


Clinical and pathomorphological aspects of odontogenic tumors.
Odontogenic tumors (OTs) comprise a group of heterogeneous lesions ranging from hamartomatous or non-neoplastic tissue proliferation to benign or malignant neoplasms with metastatic potential. OTs are derived from epithelial, ectomesenchymal, and/or mesenchymal elements of tooth-forming ("odontogenic") tissues, which show variable clinical and histopathological features. Herein, the authors summarize the World Health Organization (WHO) 2022 classification of OTs and further highlight diagnostic tips and differential clues for the most common OTs. OTs may not be commonly encountered in the daily practice of many pathologists. This makes their diagnosis challenging as there is little practice in understanding the features required for their classification. However, diagnosing the vast majority of these lesions is not difficult provided the following aspects are considered: 1) the general knowledge of tooth development; 2) a few key histological observations; 3) very basic knowledge of the clinical and especially the radiographic features with which they are associated.


Influence of blood loss on the pharmacokinetics of citalopram.
Extended blood loss results in several compensatory physiological mechanisms, including transfer of extravascular fluid into the blood circulation. If drugs are present in the body, this fluid exchange may imply that blood drug concentrations found in a trauma victim may differ from the concentrations present at the time of the trauma. To address this issue, an animal model was used to investigate the influence of blood loss on pre-existing levels of the antidepressant drug citalopram and its demethylated metabolites. Rats were administered citalopram either acutely (40 mg/kg, orally) or chronically (20 mg/kg daily, subcutaneously) for 6 days using osmotic pumps. In the experimental rats, blood loss was accomplished by withdrawing 0.8 mL blood at 10 min intervals during 70 min. In the control rats, blood was withdrawn at 0 and 70 min only. Blood, brain and lung drug concentrations were analyzed with an enantioselective HPLC method. In the chronically treated rats, the ratios between final and initial citalopram concentrations were 1.08 +/- 0.15 and 1.01 +/- 0.09 in the experimental rats and controls, respectively, indicating no major effect of blood loss. In contrast, acute oral administration resulted in increased ratios in the exsanguinated rats as compared to controls (1.84 +/- 0.50 versus 0.73 +/- 0.07; p = 0.0495). In conclusion, the observation of increased blood drug levels in the acute oral rats indicates that absorption of fluid from the gastrointestinal tract may be important in the intravascular refill. Further, in the interpretation of post-mortem blood levels of drugs, these physiological mechanisms should be taken into account.


Comprehensive review on ideas, designs and current techniques in solar dryer for food applications.
Due to the expansion of residents, the consumption of non-renewable energy increased enormously, thus indirectly increasing pollution and affecting the surroundings. To reduce pollutions in the surroundings, it is recommended to choose non-conventional energy sources. By satisfying this, we can probably decrease the non-renewable sources of energy, by consuming the solar power in day-to-day life in the application of food drying process. In this review article, we have discussed the classification of solar dryer and the impact of design modifications performed in the components of solar dryer and assessed the various types of solar dryer performance, cost estimations and designs performed in solar dryer of food applications which were not discussed in the earlier research. The primary and critical task in designing the solar dryer is to achieve higher efficiency at minimum cost. Hence, proper analysis of drying application, selection of suitable components and suitable design must be carried out to attain efficient dryer. Considering these characteristics, this paper primarily focuses on the effective design parameters incorporated with various efficiency enhancement processes of the solar dryer in the applications of food drying techniques. Thus, this review paper delivers the various classifications, design parameters, performance enhancement methods, properties and valuable assets of solar dryer, which helps to develop the sustainable green eco-friendly environment most primarily, in the application of food drying process. This review article concreted the way for upcoming considerations and provided the techniques for the studies to convey the work for promoting method enhancements.


Comparison of postoperative intraocular pressure changes between 23-gauge transconjunctival sutureless vitrectomy and conventional 20-gauge vitrectomy.
To compare the intraocular pressure (IOP) after 23-gauge transconjunctival sutureless vitrectomy (TSV) and conventional 20-gauge vitrectomy for various vitreoretinal diseases. This was a retrospective interventional case series including 338 cases of 23-gauge TSV and 476 cases of 20-gauge vitrectomy with minimum follow-up period of 1 month. Postoperative 1 day, 1 week and 1 month IOPs were compared. Multiple regression analysis to assess the actual effect of gauge of vitrectomy on postoperative IOP was performed including intraoperative and postoperative factors influencing postoperative IOP as covariates. The mean IOP of 20-gauge vitrectomy was significantly higher than that of 23-gauge TSV (20.6 ± 8.02 mm Hg vs 12.8 ± 4.48 mm Hg, P<0.001) at postoperative day 1, but the differences were not significant at postoperative 1 week and 1 month. The IOP pattern of 23-gauge TSV demonstrated more stable course than that of 20-gauge vitrectomy. At 1 day post vitrectomy, the incidence of hypertony was higher in 20-gauge, whereas that of hypotony was higher in 23-gauge. Among risk factors, the 20-gauge vitrectomy showed the strongest association with postoperative 1 day IOP rise. Twenty-three-gauge TSV has stable and lower IOP in the early postoperative period than the 20-gauge vitrectomy. In patients whose retina and optic nerves are vulnerable to higher or fluctuating IOP, 23-gauge TSV may be more beneficial.


A comparison of the different helices adopted by α- and β-peptides suggests different reasons for their stability.
The right-handed α-helix is the dominant helical fold of α-peptides, whereas the left-handed 3(14)-helix is the dominant helical fold of β-peptides. Using molecular dynamics simulations, the properties of α-helical α-peptides and 3(14)-helical β-peptides with different C-terminal protonation states and in the solvents water and methanol are compared. The observed energetic and entropic differences can be traced to differences in the polarity of the solvent-accessible surface area and, in particular, the solute dipole moments, suggesting different reasons for their stability.


COVID-19 brought the water struggles in Ghana into our homes in Canada: Collective emotions and WASH struggles in distant locations during health emergencies.
The COVID-19 pandemic has heightened and made visible the embodied consequences of water, sanitation and hygiene (WASH) inequalities and the relationalities of health in place. This paper combines insights from relational geographies and embodied epidemiology to explore psychosocial concerns among Ghanaian migrants in Canada due to their multiple and simultaneous roles in the WASH space in Ghana, particularly during the COVID-19 pandemic. We explored this using narratives from in-depth interviews with 27 participants (16 women and 11 men) residing in Ontario, Canada. The case of Ghana offers insight into how social ties with home communities could provide a safety net during emergencies but could also affect the psychosocial wellbeing of migrants. Results revealed four interrelated psychosocial stressors, including social stressors, financial stressors, stressors related to perceived inequality and stressors related to the fear of infection during WASH access. The paper underscores the urgent need for research to move beyond local health implications of WASH inequalities and begin to prioritize how these social inequalities are embodied at distant locations.


Perturbations of gut microbiome and metabolome of pigs infected with Mycoplasma hyorhinis.
Mycoplasma hyorhinis is a prevalent respiratory pathogen in swine, causing significant economic loss to pig producers. There is growing evidence that respiratory pathogen infections have a large impact on intestinal microecology. To study the effect of M. hyorhinis infection on gut microbial composition and metabolome profile, pigs were infected with M. hyorhinis. Metagenomic sequencing analysis was performed of fecal samples and a liquid chromatography/tandem mass spectrometry (LC-MS/MS) analysis of gut digesta was made. Pigs infected with M. hyorhinis had enriched Sutterella and Mailhella, and depleted Dechloromonas, Succinatimonas, Campylobacter, Blastocystis, Treponema, and Megasphaera. The pigs infected with M. hyorhinis also had greater abundances of bacterium_0_1xD8_71, Ruminococcus_sp__CAG_353, Firmicutes_bacterium_CAG_194, Firmicutes_bacterium_CAG_534, bacterium_1xD42_87, and lower abundances of Chlamydia_suis, Megasphaera_elsdenii, Treponema_porcinum, Bacteroides_sp__CAG_1060, Faecalibacterium_prausnitzii. Metabolomic analysis revealed that some lipids and lipid-like molecules increased in the small intestine, whereas most lipids and lipid-like molecule metabolites decreased in the large intestine. These altered metabolites induce changes in intestinal sphingolipid metabolism, amino acid metabolism, and thiamine metabolism. These findings demonstrate that infection with M. hyorhinis can alter the gut microbial composition and metabolite structure in pigs, which may further affect amino acid metabolism and lipid metabolism in the intestine. © 2023 Society of Chemical Industry.


PKR regulates B56(alpha)-mediated BCL2 phosphatase activity in acute lymphoblastic leukemia-derived REH cells.
Protein phosphatase 2A (PP2A) is a heterotrimer comprising catalytic, scaffold, and regulatory (B) subunits. There are at least 21 B subunit family members. Thus PP2A is actually a family of enzymes defined by which B subunit is used. The B56 family member B56alpha is a phosphoprotein that regulates dephosphorylation of BCL2. The stress kinase PKR has been shown to phosphorylate B56alpha at serine 28 in vitro, but it has been unclear how PKR might regulate the BCL2 phosphatase. In the present study, PKR regulation of B56alpha in REH cells was examined, because these cells exhibit robust BCL2 phosphatase activity. PKR was found to be basally active in REH cells as would be predicted if the kinase supports B56alpha-mediated dephosphorylation of BCL2. Suppression of PKR promoted BCL2 phosphorylation with concomitant loss of B56alpha phosphorylation at serine 28 and inhibition of mitochondrial PP2A activity. PKR supports stress signaling in REH cells, as suppression of PKR promoted chemoresistance to etoposide. Suppression of PKR promoted B56alpha proteolysis, which could be blocked by a proteasome inhibitor. However, the mechanism by which PKR supports B56alpha protein does not involve PKR-mediated phosphorylation of the B subunit at serine 28 but may involve eIF2alpha activation of AKT. Phosphorylation of serine 28 by PKR promotes mitochondrial localization of B56alpha, because wild-type but not mutant S28A B56alpha promoted mitochondrial PP2A activity. Cells expressing wild-type B56alpha but not S28A B56alpha were sensitized to etoposide. These results suggest that PKR regulates B56alpha-mediated PP2A signaling in REH cells.


Biochemical characterization and N-terminomics analysis of leukolysin, the membrane-type 6 matrix metalloprotease (MMP25): chemokine and vimentin cleavages enhance cell migration and macrophage phagocytic activities.
The neutrophil-specific protease membrane-type 6 matrix metalloproteinase (MT6-MMP)/MMP-25/leukolysin is implicated in multiple sclerosis and cancer yet remains poorly characterized. To characterize the biological roles of MT6-MMP, it is critical to identify its substrates for which only seven are currently known. Here, we biochemically characterized MT6-MMP, profiled its tissue inhibitor of metalloproteinase inhibitory spectrum, performed degradomics analyses, and screened 26 chemokines for cleavage using matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry. MT6-MMP processes seven each of the CXC and CC chemokine subfamilies. Notably, cleavage of the neutrophil chemoattractant CXCL5 activates the chemokine, thereby increasing its agonist activity, indicating a feed-forward mechanism for neutrophil recruitment. Likewise, cleavage also activated CCL15 and CCL23 to increase monocyte recruitment. Utilizing the proteomics approach proteomic identification of cleavage site specificity (PICS), we identified 286 peptidic cleavage sites spanning from P6 to P6' from which an unusual glutamate preference in P1 was identified. The degradomics screen terminal amine isotopic labeling of substrates (TAILS), which enriches for neo-N-terminal peptides of cleaved substrates, was used to identify 58 new native substrates in fibroblast secretomes after incubation with MT6-MMP. Vimentin, cystatin C, galectin-1, IGFBP-7, and secreted protein, acidic and rich in cysteine (SPARC) were among those substrates we biochemically confirmed. An extracellular "moonlighting" form of vimentin is a chemoattractant for THP-1 cells, but MT6-MMP cleavage abolished monocyte recruitment. Unexpectedly, the MT6-MMP-cleaved vimentin potently stimulated phagocytosis, which was not a property of the full-length protein. Hence, MT6-MMP regulates neutrophil and monocyte chemotaxis and by generating "eat-me" signals upon vimentin cleavage potentially increases phagocytic removal of neutrophils to resolve inflammation.


Nuclear morphometry of the myocardial cells as a diagnostic tool in cases of sudden death due to coronary thrombosis.
Sudden cardiac death due to underlying coronary artery thrombosis is one of the leading causes of death. However, in a significant percentage of individuals who died suddenly, no indication of myocardial infarction is found during post-mortem examination, especially when the time interval between appearance of symptoms and death is short. In the present study, we have evaluated certain nuclear morphometric parameters, such as, minimum, maximum, mean and standard deviation of perimeter and area in 20 individuals who died of coronary artery thrombosis, within 1 h from symptoms onset. Furthermore, the above parameters were compared with those of a control population of 20 individuals whose sudden death was caused by traffic accidents. Statistical elaboration of the results by means of t-test, Mann-Whitney (U-test) and analysis of covariance (adjusting for age), showed a statistically significant difference for all variables except for the minimum area. With stepwise discriminant analysis method, the mean perimeter was selected as the best predictor of cardiac death. Mean perimeter achieved a correct reclassification percentage (based on Fisher's linear discriminant function) of 92.5% (85% and 100% for cases and controls, respectively). Moreover, by applying the cut-off of 172 microns, we could identify the individuals who died suddenly because of coronary artery thrombosis with a specificity of 100% (sensitivity 85%, P < 0.001). Our results show that nuclear morphometry of the myocardial cells is a reliable diagnostic tool for the diagnosis of coronary thrombosis based lesion in cases of sudden death, even when methods trying to verify the presence of infarction fail to do so.


A protocol for the acute control of agitation in palliative care: a preliminary report.
Agitation is one of the most frequent causes for palliative sedation. It often requires urgent control to avoid negative consequences and even endangerment of all involved, including the patients themselves. A protocol for the control of episodes of agitation was developed, based on a previous experience. The protocol includes a combination of haloperidol and midazolam. The protocol was used 86 times in 27 patients. Each patient was sedated from 1 to 12 times, median 2 times. The median time from the beginning of sedation to the control of agitation was 15 minutes with a range from 1 minute (2 cases) to 3 hours and 5 minutes (only 1 case). In 71 cases (83%), only the first dose was needed. There were no significant complications.


Neuronal localization of metallothioneins in rat and human spinal cord.
The immunocytochemical localization of the metallothioneins (MT), a family of low molecular weight, heavy metal binding proteins, was investigated in rat and human spinal cord using two distinct antibodies. Polyclonal antibodies were raised to the peptide (SCKCKECKCTS), an epitope common to all human MT isoforms. The monoclonal antibody, E9 which recognizes a different epitope of the MT protein, was also used. Similar results were obtained with either antibody. Both antibodies recognized authentic MT from rabbit liver and horse kidney on Western blots. Immunoreactivity was localized primarily in the cytoplasm of motoneurons in the anterior horn of cervical and lumbar cord. However nuclear staining was present in some motoneurons in both rat and human cord. Intense nuclear, as well as cytoplasmic staining was seen in astrocytes. Capillary endothelia, ependymal cells, arachnoid and pia were also positive for MT.


Yoga Programme for Type 2 Diabetes Prevention (YOGA-DP): A Qualitative Study Exploring the Trial Team's Facilitators and Challenges in Conducting a Feasibility Trial in India.
In India, around 77 million people are at high risk of developing type 2 diabetes mellitus (T2DM). Yoga interventions can be effective in preventing T2DM. We conducted a feasibility randomized controlled trial (RCT) in India, and the intervention was the Yoga Programme for T2DM Prevention (YOGA-DP). This study aimed to identify and explore the facilitators and challenges in conducting the feasibility trial in India, and more specifically, to explore the perceptions and experiences of trial staff in relation to running the feasibility trial and Yoga instructors in relation to delivering the intervention. An exploratory qualitative study was conducted at two trial sites in India (Yoga centers in New Delhi and Bengaluru). Semi-structured interviews were conducted with ten participants (six trial staff and four Yoga instructors) to explore their perceptions and experiences related to the study's aim. Data were analyzed using deductive as well as inductive logic and an interpretative phenomenological approach. Feasibility-trial-related facilitators were useful participant recruitment strategies and help and support received from the trial coordination center. Intervention-related facilitators were strengths of the intervention content, structure, and delivery (including materials) and competencies of Yoga instructors. Feasibility-trial-related challenges were lack of awareness about T2DM among potential participants, stigma and fear associated with T2DM among potential participants, difficulties in explaining the research and obtaining written informed consent from potential participants, expectations and demands of potential participants and control-group participants, gender and language issues in participant recruitment, other participant recruitment-related challenges, issues in participant follow-up, and issues in data collection and trial documentation. Intervention-related challenges were the limited interest of participants in Yoga, participants' time constraints on practicing Yoga, participants' health issues hindered Yoga practice, beginners' difficulties with practicing Yoga, participants' demotivation to practice Yoga at home, issues with the Yoga practice venue, confusion regarding the intervention structure, issues with intervention materials, and the incompetence of Yoga instructors. The perceptions and experiences of trial staff and Yoga instructors helped us to understand the facilitators and challenges in running a feasibility trial and delivering the intervention for T2DM prevention, respectively. These findings and their suggestions will be used when designing the definitive RCT for evaluating YOGA-DP's effectiveness, and may be helpful to researchers planning similar trials. India (CTRI) CTRI/2019/05/018893.


A key cytosolic iron-sulfur cluster synthesis protein localizes to the mitochondrion of Toxoplasma gondii.
Iron-sulfur (Fe-S) clusters are prosthetic groups on proteins that function in a range of enzymatic and electron transfer reactions. Fe-S cluster synthesis is essential for the survival of all eukaryotes. Independent Fe-S cluster biosynthesis pathways occur in the mitochondrion, plastid, and cytosolic compartments of eukaryotic cells. Little is known about the cytosolic Fe-S cluster biosynthesis in apicomplexan parasites, the causative agents of diseases such as malaria and toxoplasmosis. NBP35 serves as a key scaffold protein on which cytosolic Fe-S clusters assemble, and has a cytosolic localization in most eukaryotes studied thus far. Unexpectedly, we found that the NBP35 homolog of the apicomplexan Toxoplasma gondii (TgNBP35) localizes to the outer mitochondrial membrane, with mitochondrial targeting mediated by an N-terminal transmembrane domain. We demonstrate that TgNBP35 is critical for parasite proliferation, but that, despite its mitochondrial localization, it is not required for Fe-S cluster synthesis in the mitochondrion. Instead, we establish that TgNBP35 is important for the biogenesis of cytosolic Fe-S proteins. Our data are consistent with TgNBP35 playing a central and specific role in cytosolic Fe-S cluster biosynthesis, and imply that the assembly of cytosolic Fe-S clusters occurs on the cytosolic face of the outer mitochondrial membrane in these parasites.


Course of lymphocytic choriomeningitis (LCM) virus infection in suckling mice treated with Bordetella pertussis vaccine.
Death occurred earlier and the mortality rate was higher in one and two-week-old mice pretreated with Bordetella pertussis vaccine and infected intracerebrally with LCM virus, than in not pretreated animals of the same litter. Pertussis vaccine treatment contributed to the course of LCM virus infection ending in lethal meningitis in suckling mice, by accelerating the development of their cellular immune response.


The Geneva Global Hub for Education in Emergencies: A new ally for education in emergencies.
This article provides an overview of the current landscape and needs for education in emergencies, as well as challenges and opportunities in today's critical juncture, in particular with the creation of a new ally for education in emergencies: the Geneva Global Hub for Education in Emergencies. It covers the disruption of education by the Covid-19 pandemic and the associated exacerbation of child-protection risks, as well as the pandemic's impact on the realization of the right to education of displaced children and youth and those living in humanitarian crises. While there is ample recognition at the international policy level of the importance of education in emergencies, major obstacles still prevail, such as continued underfunding and the underprioritization of education in humanitarian situations. As the world faces unparalleled needs, in particular during crises, and grapples to accelerate progress toward Sustainable Development Goal 4 and meet the commitments set out in the Global Compact for Refugees, new opportunities promise to tap opportune alliances, to inspire commitment, and to boost country-level impact.


Effect of dithiocarb and dimethyl sulfoxide on irreversible binding of 14C-bromobenzene to rat liver microsomal protein.
The irreversible binding of [14C]-bromobenzene to rat liver microsomal protein in vitro was inhibited by dithiocarb and DMSO. Dithiocarb suppressed this binding in a time- and concentration-dependent manner (I50 = 4.5 10(-5) M). DMSO reduced the degree of covalent binding by 61% from 5 x 10(-5) M to 8 x 10(-4) M. Dithiocarb was also effective in inhibiting irreversible binding of bromobenzene to liver protein in vivo. Our results are consistent with the hypothesis that dithiocarb exerts its antihepatotoxic efficacy by depressing microsomal mixed-function oxidase activity.


Growth and restoration of a T-tile-based 1D DNA nanotrack.
We designed an artificial one-dimensional DNA nanotrack that contains two T-motifs. It can be fabricated in a free solution and with a mica-assisted growth process. Also, we introduced a dry and wet method for the restoration of DNA nanostructures in order for them to be used in multiple applications.


Postoperative pain relief and bupivacaine plasma levels during continuous interscalene brachial plexus block.
Interscalene brachial plexus block was performed on 40 patients for prophylactic pain relief after shoulder surgery. A dose of 1.25 mg/kg of 0.5% bupivacaine was injected for the block (Group 1) and continued with an infusion of 0.25% bupivacaine 0.25 mg/kg/h (Group 2). If the postoperative analgesia was insufficient, the patients received i.m. oxycodone 0.15 mg/kg. In Group 1, one patient managed without oxycodone supplementation during the 24-h observation period compared with eight patients in Group 2 (P less than 0.01). The rest of the patients received 3.8 +/- 1.6 doses (Group 1) and 2.5 +/- 1.2 doses (Group 2) of oxycodone (P less than 0.05). At 30 min, the mean bupivacaine plasma concentration was 1.0 microgram/ml in Group 1 and 0.9 microgram/ml in Group 2. The mean plasma level of bupivacaine increased from 0.7 microgram/ml after 180 min to 1.1 micrograms/ml (P less than 0.01) after 24 h of infusion, providing some evidence of accumulation during infusion. The dizziness and confusion experienced by three patients could be associated with the local anaesthetic, as they obtained relief after the infusion was stopped.


Gastric disconnection in the management of perforated giant duodenal ulcer.
Giant duodenal ulcer is the most severe variant of peptic ulcer disease. Currently, however, no technical recommendations exist for the surgical management of perforation of these lesions. Due to the often extensive loss of duodenal substance, plication is impossible, pyloroplasty is hazardous, and duodenal closure is tenuous at best. In the absence of surgical precedent, it was thought that an ideal procedure would embody three principles: (1) defunctionalization of the upper gastrointestinal tract; (2) minimization of suture lines; and (3) control of potential fistula sites with tube enterostomies. As it finally evolved, the procedure of gastric disconnection became truncal vagectomy and antrectomy, along with tube gastrostomy, duodenostomy, and jejunostomy. Restoration of gastrointestinal continuity was deferred for 3 to 4 weeks after recovery. Four consecutive patients have been successfully managed by this technique. Gastric disconnection is physiologically sound and may prove to be superior to alternative techniques in this difficult condition.


Acute confusional state of unknown cause in the elderly: a study with continuous EEG monitoring.
Acute confusional state (ACS) is a frequent cause of emergency consultation in the elderly. Many causes of ACS are also risk factors for seizures. Both non-convulsive seizures and status epilepticus can cause acute confusion. The yield of routine EEG may not be optimal in case of prolonged post-ictal confusion. We thus, sought to evaluate the yield of CEEG in identifying seizures in elderly patients with ACS of unknown origin. We reviewed our CEEG database for patients over 75 years with ACS and collected EEG, CEEG and clinical information. Thirty-one percent (15/48) of the CEEG performed in elderly patients were done for ACS. Routine EEG did not reveal any epileptic anomalies in 7/15 patients. Among those, CEEG identified interictal epileptiform discharges (IED) in 2 and NCSE in 1. In 8/15 patients, routine EEG revealed epileptiform abnormalities: 3 with IED (including 1 with periodic lateralized discharges), 3 with non-convulsive seizures (NCSz) and 2 with non-convulsive status epilepticus (NCSE). Among patients with only IED, CEEG revealed NCSz in 1 and NCSE in 2. This retrospective study suggests that NCSz and NCSE may account for more cases of ACS than what was previously thought. A single negative routine EEG does not exclude this diagnosis. Continuous EEG (CEEG) monitoring is more revealing than routine EEG for the detection of NCSE and NCSz in confused elderly. The presence of IED in the first routine EEG strongly suggests concomitant NCSz or NCSE. Prospective studies are required to further determine the role of CEEG monitoring in the assessment of ACS in the elderly and to establish the incidence of NCSz and NCSE in this setting.


High-sensitivity lens-coupled slow-scan CCD camera for transmission electron microscopy.
A lens-coupled slow-scan CCD camera has been built for transmission electron microscopy (TEM) applications. In this design, a leaded glass window, which is coated with a 20 microns layer of red P20 phosphor, is mounted on the bottom of the microscope. A lens assembly and mirror prism, located outside the microscope vacuum below the leaded glass, relays the image onto a back-thinned 1kx1k charge-coupled device (CCD) detector. This CCD is electronically cooled to below -30 degrees C during operation. It is found that X-ray irradiation, generally found to be annoying in fiber-optically coupled CCD cameras, is completely eliminated by this configuration. The collection efficiency of this system, although not as high as some of the fiber-optically coupled CCD cameras, is high enough to achieve single-electron sensitivity under a high-gain mode.


[Osteotendocutaneous radial forearm flap for hand reconstruction following circular saw injury].
Circular saw injuries may cause severe damage to the soft tissue of the hand, including destruction of skin, tendons and bone. We report the use of an osteotendocutaneous radial forearm flap for hand reconstruction following circular saw injury. This flap allowed simultaneous reconstruction of skin, tendon and osseous defect of the metacarpal bone.


Cell Biological Analyses of Anther Morphogenesis and Pollen Viability in Arabidopsis and Rice.
Major advances have been made in our understanding of anther developmental processes in flowering plants through a combination of genetic studies, cell biological technologies, biochemical analyses, microarray and high-throughput sequencing-based approaches. In this chapter, we summarize widely used protocols for pollen viability staining, investigation of anther morphogenesis by scanning electron microscopy (SEM), light microscopy of semi-thin sections, ultrathin section-based transmission electron microscopy (TEM), TUNEL (terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate (dUTP) nick end labeling) assay for tapetum programmed cell death, and laser microdissection procedures to obtain specific cells or cell layers for transcriptome analysis.


Fibrinolytic capacity in peritoneal fluid after laparoscopic and conventional colorectal resection: data from a randomized controlled trial.
A reduced peritoneal fibrinolytic capacity after surgery is currently accepted to be the main cause for postoperative adhesions. The aim of this prospective randomized trial was to determine the fibrinolytic activity in peritoneal fluid after laparoscopic as compared to conventional colorectal resection. A randomized controlled trial in parallel with the multicenter trial Lapkon II was conducted. Peritoneal fluid was sampled via drain at 2, 8, and 24 h after elective laparoscopic (n=14; LAP) and conventional (n=16; CON) colorectal resections. Activities and concentrations of tissue plasminogen activator (t-PA), plasminogen activator inhibitor type-1 (PAI-1) and t-PA/PAI complex were determined in all specimen by ELISA kits. There was no difference in age, sex or body mass index between both groups. Postoperatively, t-PA activity decreased in both groups and was lower 2 h after closing the abdomen in the laparoscopic group (p<0.05). PAI-1 activity and concentration increased in both groups. Difference between the groups was measured for PAI-1 concentration after 24 h (p<0.05). There were no differences between the groups regarding t-PA concentrations, PAI-1 activity and t-PA/PAI complex. After closing the abdominal cavity, postoperative changes in fibrinolytic capacity of peritoneal fluid can be determined in samples collected by a drain. However, there were no major differences in the postoperative course of fibrinolytic capacity in peritoneal fluid after laparoscopic and conventional colorectal resections.


Unlocking the benefits of split gill mushroom: Chemical analysis and prebiotic properties of schizophyllan extract.
The edible split gill mushroom is considered both a nutritive and therapeutic superfood, as well as rich in schizophyllan and protein. Prebiotic properties and other biological effects distinguish the schizophyllan (β-glucan). Thus, this research investigates the identity of the mushroom strain, the nutritional composition of this mushroom, and the schizophyllan extract for further analysis, including its prebiotic activity and so on. The experimental results revealed that this mushroom was identified as Schizophyllum commune, comprising more excellent carbohydrates, protein, crude fiber, lower fat, and no heavy metal detection. Moreover, this extract consisted of pharmaceutical hydrophobin (14.0-18.5 kDa), lectin protein (21-35 kDa), bioactive purpurin or red pigment, including the prebiotic β-glucan stimulating the proliferation of probiotic bacteria isolated from yogurt. Therefore, both S. commune and the schizophyllan extract can be used as a prebiotic candidate, functional food, and nutraceutical product.


[Characteristics of habituation in visceral systems].
In anesthetized and immobilized cats, habituation of evoked responses to repeated stimulation of the splanchnic nerve occurred in the cerebral cortex. Upon cessation of the stimulation, the habituation waned spontaneously (spontaneous recovery). The rate of spontaneous recovery depended on number of habituating stimuli (effect of "below-zero"). Repeated series of habituation training produced a more rapid habituation of EPs (potentiation of habituation). An extrastimulus to cutaneous or splanchnic nerve leads to recovery of the evoked response (dehabituation or sensitization). Repeated application of the dehabituating stimulus produced a progressively lesser sensitization (habituation of dehabituation).


Radioallergosorbent testing for penicillin allergy in family practice.
To determine (a) the prevalence of patients supposedly allergic to penicillin who have a positive radioallergosorbent test (RAST) result for penicillin G or V and (b) the predictive power of family physicians' clinical judgement that a patient who is supposedly allergic to penicillin will have a positive RAST result. Prospective multicentre cross-sectional observational study. Eleven primary care practices in Newfoundland; 10 were in a rural setting. Of 110 consecutive adult patients with a supposed allergy to penicillin 97 agreed to participate in the study; 92 underwent RAST. Patients helped physicians complete a questionnaire and had a venous blood sample taken for the RAST. Physicians examined the clinical history and judged whether the patient was likely to have a positive RAST result. Rates of positive and negative RAST results for penicillin V and G. Of the 92 patients 8 had a positive RAST result and 84 a negative one. The positive predictive power of a "good" clinical history (e.g., urticaria, swollen eyes, tongue or lips, or an anaphylactic reaction witnessed by a physician) was low (10%); the negative predictive power of a "poor" clinical history (e.g., nausea, vomiting, diarrhea, fever, nonspecific rash or fainting) was 92%. Less than 10% of primary care patients with a supposed allergy to penicillin will have a positive RAST result. In addition, physicians' predictions of allergy in such patients are imprecise.


Comparison of surgical repositioning rates and outcomes for hydrophilic vs hydrophobic single-piece acrylic toric IOLs.
To evaluate the comparative rotational stability and the repositioning rates and outcomes of a hydrophilic and hydrophobic acrylic monofocal toric intraocular lens (IOLs). Single center, Aravind Eye Hospital in Madurai, India. Retrospective cohort study. All patients had either an Auroflex hydrophilic acrylic toric IOL (n = 4603) or AcrySof hydrophobic acrylic toric IOL (n = 926) implanted between January 2015 and April 2019. Surgical repositioning was offered if the toric IOL was 15 degrees or greater misaligned or there was a 2-line or greater improvement in uncorrected distance visual acuity (UDVA) predicted with repositioning. A total of 5529 single-piece toric IOLs were implanted during the study period. There was no statistically significant difference between the hydrophilic and hydrophobic acrylic toric IOL groups in need for surgical repositioning (2.5% vs 1.9%; P = .34) or actual surgical repositioning rate (1.8% vs 1.5%; P = .59). A higher rate of surgical toric IOL repositioning was associated with younger age (62.7 vs 67.2 years; P < .0001), higher presurgical astigmatism (2.32 vs 1.99 diopters [D]; P < .0001), and with-the-rule astigmatism (4.7% vs 2.1% against-the-rule astigmatism; P = .002). In 95 eyes that underwent toric IOL repositioning, there was significant preoperative to postoperative improvement in UDVA (0.48 vs 0.12 logarithm of the minimum angle of resolution; P < .001), mean residual cylinder (1.79 vs 0.7 D; P < .001), and mean toric IOL misalignment (49.7 vs 5.4 degrees; P < .001). The repositioning outcomes were statistically similar with both toric IOL models. There were no major complications or recurrent toric IOL rotation after surgical repositioning. The hydrophilic acrylic toric IOL had comparable rates of postoperative misalignment and surgical repositioning with the hydrophobic acrylic toric IOL. Early postoperative surgical repositioning was both safe and effective with both toric IOLs.


Plasmid-encoded GM-CSF induces priming of the F4(K88)-specific serum IgA response by FaeG DNA vaccination in pigs.
We have used FaeG DNA to immunise piglets by the intradermal (ID) and the intramuscular (IM) route in a heterologous prime/boost model. ID immunisation with DNA resulted in a better induction of cellular immunity, whereas only the IM immunisation could prime an F4(K88)-specific serum IgA response. However, ID administration of plasmid-encoded GM-CSF 1 week before the ID immunisation enhanced the F4-specific humoral and cellular immune response and even primed the F4-specific IgA response more efficiently than the IM immunisation did.


The relative importance of prey availability and intruder pressure in feeding territory size regulation by harriers, Circus cyaneus.
The relative importance of prey availability and intruder pressure in the regulation of harrier (Circus cyaneus) territory size was investigated over two years using analytical methods chosen to permit comparison with Myers et al. (1979) study of sanderlings (Calidris alba). Relationships between territory area and two variables, prey type (mice; large, medium, and small birds) and intruder type (conspecific neighbors, conspecific floaters, and heterospecific floaters), and the consistency of these relationships between years, also were examined. Individual harrier territory areas were highly variable, ranging from 7.8 to 1249 ha in 1984/1985, and 3.9 to 71.3 ha in 1985/1986. Of the prey variables, only mouse availability was significantly inversely correlated with territory area in both years, and slopes resulting from correlations between the logarithms of these two variables did not differ significantly from - 1, the expected result if harriers were adjusting mouse availabilities. The abundance of mice in conjunction with their greater ease of capture relative to birds made them functionally more available, and hence harriers' primary prey. This may explain why mice, rather than birds, were apparently the defended resource. Of the intruder variables, neighbor variables were most strongly inversely cortelatd with territory area. Partial correlation analyses to determine the relative importance of intruder pressure and prey availability in regulating territory size revealed that in 1984/1985, mouse availability and intruder pressure were relatively independent and each explained some variation in territory area, whereas in 1985/1986, mouse availability, rather than intruder pressure, significantly explained all variation in territory area. Possible explanations for why territory sizes of harriers appear to be regulated more closely by food density, whereas territory sizes of sanderlings appear to be regulated more closely by intruder pressure, are based upon differences in 1) neighbor effects, 2) environmental ronmental variability, and 3) accuracy of resource assessment by intruders. The variation in intruder rates and prey availabilities observed between years suggests the need to conduct studies over several years in order to assess accurately the relative importance of these variables in territory-size regulation.