Mechanism of noradrenaline-induced heterologous desensitization of adenylate cyclase stimulation in rat heart muscle cells: increase in the level of inhibitory G-protein alpha-subunits.
The mechanism of heterologous desensitization of adenylate cyclase stimulation was studied in cultured neonatal rat heart muscle cells. After culturing of the cells for 3 days in the presence of 1 microM noradrenaline there was in addition to a 52% decrease in isoproterenol-stimulated adenylate cyclase activity, a lessening of the stimulation of beta-adrenoceptor-independent adenylate cyclase by guanosine-5'-O-(thiotriphosphate) and forskolin by 24 and 34%, respectively. The decrease in receptor-independent adenylate cyclase stimulation by forskolin, but not the attenuation of isoproterenol-stimulated adenylate cyclase activity, was abolished by pertussis toxin (PTX) pretreatment of the cells. Gi, the inhibitory G-protein of adenylate cyclase was therefore quantitated. Labelling of the Mr approximately 40 kDa PTX substrates in membranes of noradrenaline-treated cells was increased by 70% as shown by pertussis toxin-catalyzed ADP ribosylation of heart cell membranes. This increase was also seen in the presence of an excess of purified beta gamma-subunits of transducin and of GTP, suggesting that the increased labelling was not due to elevation of the level of beta gamma-subunits or increase in the concentration of GTP in the membranes of noradrenaline-treated cells. Analysis of the PTX substrates on high resolution urea/SDS-polyacrylamide gels revealed that at least two distinct PTX substrates (40 and 41 kDa) were present in rat heart cell membranes. The labelling of both substrates was increased in membranes of desensitized cells. Immunoblotting of heart cell membranes with anti-Gi alpha-antibodies demonstrated a marked increase in the amount of Gi alpha in membranes of noradrenaline-treated cells. In contrast, immunoblotting with anti-beta-antibodies showed that the level of the beta-subunit of G-proteins (36 kDa) was unchanged after noradrenaline exposure. The data indicate that prolonged treatment of rat heart muscle cells with noradrenaline leads to an increase in the level of alpha-subunits of Gi-proteins. This suggests that this increase is responsible for the observed heterologous desensitization of adenylate cyclase stimulation.


Could positive diurnal variations in severe depression be the key factor for delivering effective cognitive behaviour therapy?
Cognitive behaviour therapy (CBT) has been demonstrated to be the leader in the field of talking therapies concerned with the treatment of severe depression. However, this form of therapy has its limitations in that it is ineffective if given during a severe depressive episode. This is usually because patients suffering from severe depression have difficulties in concentration which severely limits the ability to take in new information such as the practice of strategies that encourage more helpful ways of thinking which could aid recovery. The severely depressed patient who experiences diurnal variations typically experiences low mood in the morning but mood improves towards the evening. Conversely, there are cases where mood is better in the morning becoming worse in the evening. There can be cases of positive diurnal rhythms where adverse symptoms disappear all together and the patient regains something resembling their pre-morbid normality. With this lifting of mood, it could mean that the patient may be more receptive to absorbing new information. Consequently, the hypothesis is that when patients are experiencing positive diurnal rhythms, this could be the optimum time to deliver effective talking treatments such as CBT.


Hemorheology in patients with liver cirrhosis: special emphasis on its relation to severity of esophageal variceal bleeding.
Patients with decreased blood viscosity are supposed to have a higher risk of bleeding and increased severity of bleeding (severity of bleeding proportional to transmural pressure x area of variceal tear/blood viscosity). However, the hemorheological factors have never been assessed in patients with esophageal variceal bleeding. Therefore, the purpose of the present study was to examine the hemorheological factors in liver cirrhotic patients with special emphasis on the outcome of variceal bleeding. Forty-two liver cirrhosis patients with variceal bleeding and another 44 matched patients without bleeding were enrolled. The hemorheological and hemostatic factors of their peripheral blood were examined. The clinical course was under careful surveillance. Patients with poor hepatic reserve (Child B + C vs A) had lower whole blood viscosity (4.34 +/- 0.56 mPa.s vs 5.06 +/- 1.35 mPa.s, P < 0.05), lower hematocrit levels (32.86 +/- 5.97% vs 36.62 +/- 5.44%, P < 0.05), lower platelet counts (79.7 +/- 47.6 x 10(3)/mL vs 108.0 +/- 71.2 x 10(3)/mL, P < 0.05) and prolonged prothrombin time (2.88 +/- 2.33 s vs 1.27 +/- 1.37 s, P < 0.05). Patients with bleeding (vs non-bleeding group) had lower hematocrit levels (31.44 +/- 5.75% vs 36.57 +/- 5.19%, P < 0.01) and lower fibrinogen levels (226.7 +/- 92.7 mg/dL vs 286.4 +/- 111.8 mg/dL, P < 0.05). Patients with bleeding with shock had worse liver cirrhosis (Child A/B/C = 0/5/4 vs 11/18/4, P < 0.05), lower whole blood viscosity (4.01 +/- 0.17 mPa.s vs 4.57 +/- 0.76 mPa.s, P < 0.05), reduced erythrocyte aggregability (2.94 +/- 0.41 vs 3.54 +/- 0.61, P < 0.001), and lower platelet counts (56.22 +/- 17.05 x 10(3)/mL vs 88.87 +/- 38.12 x 10(3)/mL, P < 0.001). The Child-Pugh grade and erythrocyte aggregability were two independent factors associated with bleeding shock. Whole blood viscosity, hematocrit levels and platelet counts were lower in patients with advanced liver cirrhosis. Advanced liver cirrhosis and reduced erythrocyte aggregability were independent factors for hypovolemic shock in cirrhotic patients with esophageal variceal bleeding. However, the causal relationship between hemorheology and bleeding needs to be clarified in further studies.


Evaluation of nonlinear dynamics in postural steadiness time series.
Fractal and correlation dimensions have been computed for time series obtained from tests of balance (postural steadiness). Although these measures appear to be reliable and differentiate subject groups, it has become clear that random (noise) time series may have finite dimensions and appear to demonstrate dynamics characteristic of nonlinear systems. Consequently, it is necessary to apply a test to distinguish a time series with putative nonlinear dynamics from random noise. A simple predictor was utilized to compare center of pressure (COP) time series with surrogate data constructed to have similar time and frequency domain characteristics. It was found that the original time series was more predictable than the surrogate data, suggesting that the COP data is derived from a nonlinear system.


Robotic versus open approach in total gastrectomy for gastric cancer: a comparative single-center study of perioperative outcomes.
The robotic approach to gastric cancer has been gaining interest in recent years; however, its benefit over the open procedure in total gastrectomy with D2 lymphadenectomy is still controversial. The aims of the study were to compare postoperative morbidity and mortality, hospital stay, and anatomopathological findings between the robotic and open approaches to oncologic total gastrectomy. We analyzed a prospectively collected database, which included patients who underwent total gastrectomy with D2 lymphadenectomy in our center using a robotic or an open approach between 2014 and 2021. Comparative analysis of clinicopathological, intraoperative, postoperative and anatomopathological variables between the robot-assisted group and the open group was performed. Thirty patients underwent total gastrectomy with D2 lymphadenectomy by a robotic approach and 48 patients by an open procedure. Both groups were comparable. The robot-assisted group presented a lower rate of Clavien-Dindo complications ≥ stage II (20 vs. 48%, p = 0.048), a shorter hospital stay (7 days vs. 9 days, p = 0.003) and had a higher total number of lymph nodes resected (22 nodes vs. 15 nodes, p = 0.001) compared to the open approach. Operative time was longer in the robotic group (325 min vs. 195 min, p < 0.001) compared to the open group. The robotic approach is associated with a longer surgical time, a lower rate of Clavien-Dindo complications ≥ stage II and a shorter hospital stay, and more lymph nodes were resected compared to the open approach.


Safety in Dermatologic Procedures: How to Prevent, Recognize, and Treat Bleeding Complications in Dermatologic Surgery.
Bleeding complications during dermatologic surgery are uncommon and usually minor, but bleeding occasionally leads to infection, wound dehiscence, or flap/graft necrosis. This review covers the keys to preventing, recognizing, and treating excessive bleeding during and after surgery.


Transcriptomic Approach for Global Distribution of SNP/Indel and Plant Genotyping.
Single Nucleotide Polymorphisms (SNPs) are the most common structural variants found in any genome. They have been used for different genetic studies, from the understanding of genetic structure of populations to the development of breeding selection markers. In this chapter we present the use of transcriptomic data obtained from contrasting phenotypes for a target trait, in searching of SNPs and insertions/deletions (InDels). This approach has the advantage that the identified markers are in or close to differentially expressed genes, and so they have higher chances to tag the genes underlying the phenotypic expression of a particular trait.


Hemolytic-uremic syndrome associated with pancreatitis in an HIV-positive patient.
Hemolytic-uremic syndrome (HUS) is a newly recognized hematologic manifestation of HIV infection that may be triggered by local or systemic infections as well as by immunological disorders. We report the case of a 36-year-old HIV-positive man, an intravenous drug abuser who developed HUS during an episode of acute pancreatitis. Hematologic and clinical improvement occurred following 2 weeks of nonaggressive therapy including vitamin E and fresh-frozen plasma.


Fistula Fortnight: innovative partnership brings mass treatment and public awareness towards ending obstetric fistula.
As part of the global Campaign to End Fistula, the Fistula Fortnight, a 2-week mass obstetric fistula treatment project, was organized in northern Nigeria to contribute to reducing the backlog of untreated fistulas and raise awareness regarding obstetric fistulas and safe motherhood. An array of partners joined forces to provide free surgical treatment, strengthen the capacity of existing facilities to manage obstetric fistulas, and utilize media strategies to raise awareness. The Fistula Fortnight took place from February 21 to March 6, 2005, at 4 established fistula repair centers in the northern Nigeria states of Kano, Katsina, Kebbi, and Sokoto. A total of 569 women received treatment, with an 87.8% rate of successful closures. The highly publicized event also raised awareness on the issue of obstetric fistula and helped put a face to maternal deaths. The Fortnight, which required extensive and thoughtful planning involving many persons cognizant of health system and quality of care issues, was effective in drawing attention to the vast fistula problem and contributed to reducing the backlog of patients.


No seasonal influence on cognitive performance in a national sample of older adults in New Zealand.
A recent North American study reported seasonal differences in cognitive functioning in older adults. We assessed seasonality of cognitive functioning in a large data set of older adults in New Zealand. The International Residential Assessment Instrument-Home Care (interRAI-HC) data set was analysed using a non-parametric method for testing seasonal distribution of cognitive and depression scale scores. Participants were 73 285 New Zealanders 65 years and older who completed their first interRAI-HC assessment (mean age, 81.4 years; 57% female). We analysed this sample cross-tabulating season (summer, autumn, winter and spring) and the Cognitive Performance Scale (CPS) score (Kruskal-Wallis test, P = 0.45). Month-by-month CPS scores also demonstrated no variation (Spearman's test, P = 0.96). There was no association between season of assessment and the Depression Rating Scale score, ruling out variability in affect impacting on cognitive performance (Kruskal-Wallis test, P = 0.99). Our findings, limited to the Southern Hemisphere, demonstrate a lack of seasonality in cognitive performance and impairment in older adults.


The discovery of ghrelin--a personal memory.
The endogenous ligand for growth-hormone secretagogue receptor (GHS-R) was purified from the stomach and named it "ghrelin," after the word root "ghre" in Proto-Indo-European languages meaning "grow", since ghrelin has potent growth hormone (GH) releasing activity. Ghrelin plays important roles for maintaining growth hormone release and energy homeostasis in vertebrates. In this essay, I described my personal memory on the discovery of ghrelin in the year 1999.


The effect of social exclusion on state paranoia and explicit and implicit self-esteem in a non-clinical sample.
The relationship between self-esteem and paranoia may be influenced by social stress. This study aimed to replicate previous research on the impact ofsocial exclusion on paranoia and self-esteem in a non-clinical sample and to extend this work by examining the effect of exclusion on self-esteem at the 'implicit' level. Non-clinical participants (N = 85) were randomly allocated to the Inclusion or Exclusion condition of a virtual ball-toss game ('Cyberball'). They completed self-reportmeasures of state paranoia and self-esteem, and two implicit measures of self-esteem - theImplicit Association Task (IAT) and Implicit Relational Assessment Procedure (IRAP) -prior to and after exposure to Cyberball. Social exclusion increased state paranoia. This effect was moderated by distress associated with trait paranoia. Exclusion was also associated with decreased self-reported self-esteem, as well as reduced implicit self-esteem on the IAT. Changes in self-reported self-esteem were associated with state paranoia at post-Cyberball. The IRAP indicated that reductions in implicit self-esteem may be due to increases in 'Me-Negative' and 'Others-Positive' biases (rather than reductions in 'Me-Positive' bias). The current study involved a non-clinical sample and so findings cannot be generalized to clinical paranoia. These findings are consistent with previous evidence that paranoia is associated with negative self-evaluations, whereas positive self-evaluations can persist in paranoia. They also provide support for the suggestion that investigations of self-esteem in paranoia should extend beyond global self-esteem and might benefit from a distinction between positive and negative components.


Identification of core protein, an intermediate in proteoglycan biosynthesis in cultured chondrocytes from the Swarm rat chondrosarcoma.
After incubating cultured chondrocytes from the Swarm rat chondrosarcoma for 30 min with [3H]serine, a labeled macromolecule was found predominantly as Mr = approximately 370,000 species which was subsequently identified as a core protein precursor to cartilage proteoglycan from the following properties: (a) it was immunoprecipitated along with completed proteoglycan from cell extracts by an antiserum to the complex of hyaluronic acid-binding region, link protein, and hyaluronic acid. Its immunoprecipitation could be inhibited completely by the addition of purified hyaluronic acid-binding region to the extracts, indicating the presence of common antigenic determinants with this region of the proteoglycan core protein. (b) the core protein precursor was able to interact with the hyaluronic acid and link protein in proteoglycan aggregates added as carrier to extracts to form mixed aggregates of high buoyant density in associative CsCl density gradients. Labeled core protein precursor and link protein were subsequently isolated from the mixed aggregates from the top of dissociative CsCl density gradients. (c) radioactivity in core protein precursor after a 30-min pulse of [3H]serine disappeared after inhibiting further protein synthesis with cycloheximide concurrent with the appearance of label in completed proteoglycan molecules.


Life expectancy at the age of 65 years and environmental factors: an ecological study in Japan.
The purpose of this study was to examine the factors associated with life expectancy at the age of 65 years used as the index of longevity, using published data in Japan. Life expectancy at the age of 65 years was obtained from the 19th life table in 2000 published by the Ministry of Health, Labour and Welfare of Japan. The associations between life expectancy at the age of 65 years and environmental factors were assessed by Spearman correlation coefficients. Life expectancy at the age of 65 years was higher in females (22.54 years) than in males (17.42 years). In this study, the number of public health nurses and leisure time per day were found significantly associated with life expectancy at the age of 65 years in both men and women. For men, life expectancy at the age of 65 years was significantly associated with leisure time for sports and exercises and higher proportion of participation in volunteer activities in the community; for women, it was associated with a higher number of hospitals and proportion of participation in educational classes for the aged. Our ecological study might provide some clues to more practical planning for longevity in consideration of gender differences.


Health workers readiness and practice in malaria case detection and appropriate treatment: a meta-analysis and meta-regression.
Health workers (HWs) appropriate malaria case management includes early detection and prompt treatment with appropriate anti-malarial drugs. Subsequently, HWs readiness and practice are considered authentic evidence to measure the health system performance regarding malaria control programme milestones and to issue malaria elimination certification. There is no comprehensive evidence based on meta-analysis, to measure the performance of HWs in case management of malaria. This study aimed to evaluate HWs performance in early malaria case detection (testing) and the appropriate treatment. The published literature in English was systematically searched from Medline, Scopus, Embase, and Malaria Journal up to 30th December 2020. The inclusion criteria were any studies that assessed HWs practice in early case detection by malaria testing and appropriate treatment. Eligibility assessment of records was performed independently in a blinded, standardized way by two reviewers. Pooled prevalence estimates were stratified by HWs cadre type. Meta-regression analysis was performed to explore the impact of the appropriateness of the method and risk of bias as potential sources of the heterogeneity in the presence of effective factors. The study pooled data of 9245 HWs obtained from 15 included studies. No study has been found in eliminating settings. The pooled estimate for appropriate malaria treatment and malaria testing were 60%; 95% CI: 53-67% and 57%; 95% CI: 49-65%, respectively. In the final multivariable meta-regression, HWs cadre and numbers, appropriateness of study methods, malaria morbidity and mortality, total admissions of malaria suspected cases, gross domestic product, availability of anti-malarial drugs, and year of the publication were explained 85 and 83% of the total variance between studies and potential sources of the heterogeneity for malaria testing and treating, respectively. HWs adherence to appropriate malaria case management guidelines were generally low while no study has been found in eliminating countries. Studies with the inappropriateness methods and risk of bias could be overestimating the actual proportion of malaria appropriate testing and treating. Strategies that focus on improving readiness and early identification of acute febrile diseases especially in the countries that progress to malaria elimination should be highly promoted.


Zootoxic effects of reduviid Rhynocoris marginatus (Fab.) (Hemiptera: Reduviidae) venomous saliva on Spodoptera litura (Fab.).
Rhynocoris marginatus is a predominant and potential reduviid predator of many economically important pests in India. The venomous saliva (VS) was collected by milking method and diluted with HPLC grade water to prepare different concentrations (200, 400, 600, 800 and 1000ppm). The VS from R. marginatus was found to be toxic and the LD(50) of the VS in Spodoptera litura third instar were 768 and 929ppm at 48 and 96h for microinjection and oral toxicity studies, respectively. Level of hydrolase and detoxification enzymes significantly decreased in a dose-dependent manner after treating the host with VS for 96h. A decrease in carbohydrate (21%) and lipid (46%) contents and an increase in the protein content (50%) were prominent in the experimental category. The VS reduced the relative growth rate, approximate digestibility, efficiency of conversion of ingested and digested food of S. litura in the oral toxicity study. Salivary venom inhibits the haemocytes from aggregation and affects spreading behavior of haemocytes separated from the fifth stadium larvae of S. litura. The result showed that VS toxins caused mortality, changed the nutritional indices, and altered the levels of macromolecule quantity and digestive enzymes of S. litura. We concluded that the VS of R. marginatus is venomous to a prey species, S. litura.


The effects of a 30 day period of environmental diversity on well-fed and previously undernourished rats: neuronal and synaptic measures in the visual cortex (area 17).
Black and white Lister hooded rats were undernourished from the 16th day of gestation until 25 postnatal days of age. These previously undernourished rats and a set of well-fed rats were later subjected to 30 days of environmental diversity, i.e., environmental enrichment or isolation. Two separate experiments were carried out. In experiment 1, the environmental diversity lasted from 85 to 115 days of age and in experiment 2, from 35 to 65 days of age. At the end of the period of environmental diversity, all rats were killed by perfusion with 2% phosphate-buffered glutaraldehyde. Small pieces of tissue from the right visual cortex were embedded in Spurr's resin. For each rat two blocks of resin-embedded tissue were randomly selected, and from these semithin sections (0.5 micron) were cut and stained with toluidine blue. Photomicrographs of cortical layers II and III were taken from these sections and used to estimate the numerical density of neurons. Ultrathin (ca. 70 nm) sections of the same region of the cortex were cut and stained with lead citrate. These sections were used to estimate the synaptic disc diameter and numerical density. Synapse-to-neuron ratios were calculated from the estimates of synaptic and neuronal numerical densities. In experiment 1, well-fed rats raised in enriched environments had a significantly smaller neuronal numerical density and a greater synaptic disc diameter than well-fed rats raised in an impoverished environment. In experiment 2, neither the well-fed nor previously undernourished rats showed significant effects of environmental treatment on any of the features studied. The statistical interaction between nutrition and environment was not significant for any of the features in either experiment.


An unusual case of vaginal myoma presenting with postmenopausal bleeding.
Vaginal leiomyomas are uncommon benign tumour with variable clinical presentation. These tumours arise most commonly from anterior vaginal wall. We report a case of 50-year old postmenopausal woman who presented with urinary retention, profuse vaginal bleeding and mass protruding into vagina. Local examination revealed a pedunculated mass attached to the posterior vaginal wall with vascular stalk one cm below the cervix. Mass was hanging outside vulva and vascular pedicle was profusely bleeding. The pedicle was ligated and tumour was excised. Subsequent histopathology revealed a vaginal myoma.


Systemic manifestations in localized scleroderma.
In this paper, the various systemic manifestations reported in localized scleroderma, their incidence, their relationship with systemic sclerosis, and their relationship with other autoimmune or connective tissue diseases will be analyzed.


The Indicators of Clinical and Subclinical Mastitis in Equine Milk.
The somatic cell count in milk (SCC) and electrical conductivity of milk (ECM) are indicators of the health status of the mammary gland. Among somatic cells, mainly polymorphonuclear neutrophils (PMN), macrophages (MAC), and lymphocytes (LYM) are rated. This study aimed to determine the SCC, PMN, MAC, LYM, ECM, and bacteriological index (BII) in milk collected from mares with (CM) and without (NCM) clinical symptoms of mastitis concerning mares with (SM) and without (NSM) subclinical mastitis. Milk samples were collected from 27 mares divided into NCM (n = 12) and CM (n = 15) groups. In samples, SCC quantification, cytological examinations, ECM measurement, and bacteriological examination were performed. In NCM mares, the values of SCC, PMN, MAC, LYM, and ECM were higher in initial than in consecutive examined days after birth until weaning. After weaning the proportion of SCC, PMN, MAC, LYM, ECM, and BII increased and did not differ with the average values in CM mares. These equine milk indicators may reflect an early symptom of subclinical mastitis and in the future may be used in the early detection of mastitis or as a tool of assessment of the health status of the mammary gland in the dairy equine farm.


High Content Screening of Mammalian Primary Cortical Neurons.
High Content Screening (HCS) can be used to analyze the morphology of neuronal primary cultures on a large scale. When used in the field of neuronal regeneration this approach allows the screening of hundreds or thousands of perturbagens, such as miRNAs, cDNAs, or compounds, for their ability to induce neuronal growth. One of the most important steps while designing these kinds of experiments is the choice of the correct neuronal model. Testing the correct neuronal type is critical to obtain results that are biologically significant and that can later be translated to a clinical setting. For example, if the goal is identifying possible therapies for Spinal Cord Injury (SCI), a challenging target is the neuronal projection from the motor cortex to the spinal cord, the corticospinal tract. Here, we describe the experimental protocols that can be used to produce primary cortical culture from young rat cortices, electroporate the neurons to study the effect of altered gene expression on neurite growth, and immunostain to measure neurite growth parameters.


Determination of cardiac ejection fraction and left ventricular volume: contrast-enhanced ultrafast cine MR imaging vs IV digital subtraction ventriculography.
To assess the accuracy of contrast-enhanced, single breath-hold cine MR imaging in the calculation of left ventricular volume and ejection fraction, we compared values obtained by using this method with those obtained by using IV digital subtraction angiography (IV-DSA). All patients (n = 28) had conventional cine and contrast-enhanced ultrafast cine MR imaging. For ultrafast cine MR imaging, a phase-rewind gradient-echo (rewind-SMASH) sequence was used: TR, 8 msec (standard excitation and acquisition block of 6 msec with phase rewind pulse of 2 msec); TE, 3.2 msec; a 128 x 96 matrix (pile encode factor, 6; k-space segment, 16); a 200-mm field of view; and one excitation. Values for left ventricular volume and ejection fraction obtained with ultrafast cine MR imaging correlated well with those obtained with IV-DSA (end-diastolic volume, y = 0.986x - 7.79, r = .985; end-systolic volume, y = 0.863x + 0.71, r = .984; ejection fraction, y = 0.877x + 6.44, r = .887). In the calculation of left ventricular volume by the area-length method, manual tracing of the left ventricular cavity was more difficult when the conventional cine method was used than when the enhanced ultrafast cine method was used. Our results show that cardiac multiphase study with horizontal long-axis, first-pass, contrast-enhanced, single breath-hold, cine MR imaging is an accurate and highly reproducible method of evaluating left ventricular volume and ejection fraction.


Correlation of interstitial pneumonia with human cytomegalovirus-induced lung infection and graft-versus-host disease after bone marrow transplantation.
In a retrospective analysis lung biopsy specimens obtained postmortem from 30 consecutive allogeneic bone marrow transplant recipients who had died of either either interstitial pneumonitis (IP; 18/30 patients) or various other causes (12/30 patients) were studied for the local presence of human cytomegalovirus (HCMV) by culture, in situ hybridization, polymerase chain reaction (PCR) and immunohistochemistry for HCMV proteins. All patients suffering from IP were found to be HCMV positive in the lung biopsy. PCR revealed the highest sensitivity for HCMV detection in lung biopsies, but in 15/18 PCR-positive samples local HCMV infection could be confirmed by at least one additional technique. All the lung biopsies obtained from the 12 patients without IP were negative for HCMV by all techniques applied, except one with a weak HCMV-DNA signal in the PCR assay. The severity of the clinical, as well as histological and immunohistological alterations in the lung did not correlate with the amount of HCMV-DNA or the number of HCMV-positive cells detected in the biopsy. An increase of HLA-class II antigen and of ICAM-1 expression on the alveolar epithelium, as well as presence of activated CD8+ or CD4+ lymphocytes infiltrating only HCMV-positive lung biopsies revealed T cell-mediated immune reactions to be involved in the pathogenesis of IP. Since all analyzed patients presented with severe acute or extensive chronic graft-versus-host disease (GvHD), but only those with pulmonary HCMV infection developed IP, dissemination of HCMV appears to be the primary requirement for the initiation of IP. GvHD, however, may interfere with normal control of subsequent antiviral immune response and, thus, provoke the immunopathology of IP.


Changes in percutaneous approach to kidney stones in children: A single institute experience over 500 cases.
The aim of this study is to identify the changes in patient age and stone sizes with technological advancement over time. This study was conducted retrospectively with 404 patients (504 renal units) who underwent percutaneous nephrolithotomy (PCNL) between January 1997 and June 2020. Patient characteristics and trends on instrument preferences were investigated. Median age was 7 (1-18) years. Male to female ratio was 1.48:1 (301/203). Median stone burden was 2 cm2 (0.20-25) and median operative time was 90 minutes (20-240). The stone-free rate was 74.6%. Patients were divided into four groups according to the size of the instrument. It was found that the size of sheath used increased significantly with increasing age and stone burden. The micro-PCNL group had the shortest hospitalisation and lowest blood transfusion rate. Chronologically categorised four equal groups were compared to analyse changing patient profiles and trends. Median patient age, stone burden, operation time, sheath size, blood transfusion and complication rates decreased significantly with time. However, the use of tracts smaller than 20F and the number of patients with previous intervention increased significantly. Our study demonstrated that the patient's age and stone size at the time of initial diagnosis decrease over time while miniaturisation techniques increase in paediatric urology.


Prognostic Significance of Pretreatment Lymphocyte-to-Monocyte Ratio in Patients with Tongue Cancer.
Low pre-operative lymphocyte-to-monocyte ratio (LMR) is associated with worse outcomes in several malignancies. The aim of this study was to determine the prognostic value of LMR in tongue cancer. A total of 103 patients with pathologically-proven tongue cancer were retrospectively analyzed. The peripheral LMR and the ratio of CD8-positive to CD14-positive (CD8+/CD14+) tumor-infiltrating cells were determined by immunohistochemical staining. Receiver operating characteristic curve analysis, log-rank test, and Cox proportional hazards regression models were used for statistical analysis. There was a significant difference in overall survival (OS) between low LMR and high LMR, and low CD8+/CD14+ tumor-infiltrating cells and high CD8+/CD14+ tumor infiltrating cells. For the clinical analysis, multivariate analysis showed that clinical ocular inspection type and low LMR were independent predictors for poor OS. Concerning the immunohistochemical analysis, monocyte count was independent predictor of poor OS. Pre-operative LMR and CD8+/CD14+ tumor-infiltrating cells serve as independent prognostic biomarkers.


Results of cerebrospinal fluid analysis, neurologic examination findings, and age at the onset of seizures as predictors for results of magnetic resonance imaging of the brain in dogs examined because of seizures: 115 cases (1992-2000).
To determine whether neurologic examination findings, results of CSF analysis, or age at the onset of seizures could be used to predict whether results of magnetic resonance imaging (MRI) would be normal or abnormal in dogs with seizures. Retrospective study. 115 dogs. Information on results of neurologic examination, results of CSF analysis, age at the onset of seizures, and results of MRI was obtained from the medical records. Results of MRI were abnormal in 61 dogs and normal in 54. Sensitivity and specificity of neurologic examination alone were 77 (47/61) and 91% (49/54), respectively. Sensitivity and specificity of CSF analysis alone were 79 (48/61) and 69% (37/54), respectively. Results of MRI were abnormal for 12 of 28 (43%) dogs with abnormal CSF analysis results and normal neurologic examination results but for only 2 of 35 (6%) dogs with normal CSF analysis and normal neurologic examination results. Similarly, results of MRI were abnormal for 36 of 37 (97%) dogs with abnormal CSF analysis and abnormal neurologic examination results but for only 11 of 15 (73%) dogs with normal CSF analysis results and abnormal neurologic examination results. Age at the onset of seizures (< 6 vs > or = 6 years old) was not significantly associated with results of MRI. Results suggest that neurologic examination findings and results of CSF analysis are useful in predicting whether results of MRI will be abnormal in dogs examined because of seizures, but age at the onset of seizures is not.


Corneal transplantation for herpes simplex keratitis.
We conducted a retrospective study of 107 penetrating keratoplasties in 99 eyes (99 patients) performed from 1970 to 1979 at the Wills Eye Hospital. The follow-up periods ranged from one to 12 years (median, three years). Overall, 86 of the 107 transplants (80%) remained clear and 63 eyes (59%) achieved good to excellent visual acuities (20/60 or better). Preoperative vascularization was not a significant prognostic factor with regard to final visual outcome, graft clarity, or graft rejection. Herpes simplex keratitis was inactive at the time of corneal transplantation in 100 of the eyes (93%). The overall rate of recurrent dendritic keratitis after transplantation for herpes was 19%.


Anti-inflammatory activity of orpanoxin administered orally and topically to rodents.
Orpanoxin, a nonsteroidal anti-inflammatory drug (NSAID) lacking gastric ulcerogenic effects in the therapeutic dose range in rats, was compared with six reference NSAIDs for oral activity in the rat paw carrageenin-induced edema assay. Tested NSAIDs were ranked on the basis of oral mg/kg ED50 values: piroxicam, 0.55; orpanoxin, 35.6; diflunisal, 59.6; benoxaprofen, greater than 300; tolmetin sodium, greater than 300; and sulindac, greater than 300. Zomepirac sodium was inactive. Only the three most potent compounds produced greater than 60% inhibition of edema. Inhibition was generally greater at 4 h than at 6 h post carrageenin for all compounds. Oral activity of orpanoxin was also demonstrated in the guinea-pig u.v.-induced erythema model (ED50 = 24.2 mg/kg p.o. when given 1 h before irradiation) and in the mouse ear croton oil induced edema test (ED50 value = 131 mg/kg p.o.). Topical activity of orpanoxin was assessed in both the guinea-pig and mouse models. In the guinea-pig u.v.-induced erythema model, application (1 h after u.v.) of 1, 5, and 10% (w/v) orpanoxin creams (containing 10% urea) significantly inhibited erythema at 2, 3, and 4 h post-irradiation. Orpanoxin, mefenamic acid, and indomethacin as 1% creams inhibited total erythema scores 70, 92 and 74%, respectively. Evidence for topical activity in the mouse ear assay was also obtained for orpanoxin in diethyl ether or 10% urea cream, but not in dimethylsulfoxide. It was concluded that orpanoxin has anti-inflammatory activity comparable to reference NSAIDs in the rat paw edema test, is active orally in rat, mouse, and guinea-pig models, and shows topical activity in the guinea-pig and the mouse.


Trapezio metacarpal instability and arthritis: etiopathogenetic interpretation and surgical technique.
Trapezio metacarpal joint (TMJ) arthritis depends on various etiologies including joint laxity, repetitive stresses, hypoplasia of the trapezium bone, and musculotendinous anomalies. The anatomy of the musculotendinous insertions described in textbooks is found very seldom in reality. Only in 2 cases out of 100 hand dissections did we find 1 abductor pollicis longus (APL) tendon. The number of tendons of the first wrist compartment averaged more than four, in different arrangements.


An edge-based interface-tracking method for multiphase flows.
We propose a novel class of edge-based interface-tracking (EBIT) methods in the field of multiphase flows for advecting the interface. The position of the interface is tracked by marker points located on the edges of the underlying grid, making the method flexible with respect to the choice of spatial discretization and suitable for parallel computation. In this article we present a simple EBIT method based on two-dimensional Cartesian grids and on a linear interface representation.


Adverse metabolic and cardiovascular consequences of circadian misalignment.
There is considerable epidemiological evidence that shift work is associated with increased risk for obesity, diabetes, and cardiovascular disease, perhaps the result of physiologic maladaptation to chronically sleeping and eating at abnormal circadian times. To begin to understand underlying mechanisms, we determined the effects of such misalignment between behavioral cycles (fasting/feeding and sleep/wake cycles) and endogenous circadian cycles on metabolic, autonomic, and endocrine predictors of obesity, diabetes, and cardiovascular risk. Ten adults (5 female) underwent a 10-day laboratory protocol, wherein subjects ate and slept at all phases of the circadian cycle-achieved by scheduling a recurring 28-h "day." Subjects ate 4 isocaloric meals each 28-h "day." For 8 days, plasma leptin, insulin, glucose, and cortisol were measured hourly, urinary catecholamines 2 hourly (totaling approximately 1,000 assays/subject), and blood pressure, heart rate, cardiac vagal modulation, oxygen consumption, respiratory exchange ratio, and polysomnographic sleep daily. Core body temperature was recorded continuously for 10 days to assess circadian phase. Circadian misalignment, when subjects ate and slept approximately 12 h out of phase from their habitual times, systematically decreased leptin (-17%, P < 0.001), increased glucose (+6%, P < 0.001) despite increased insulin (+22%, P = 0.006), completely reversed the daily cortisol rhythm (P < 0.001), increased mean arterial pressure (+3%, P = 0.001), and reduced sleep efficiency (-20%, P < 0.002). Notably, circadian misalignment caused 3 of 8 subjects (with sufficient available data) to exhibit postprandial glucose responses in the range typical of a prediabetic state. These findings demonstrate the adverse cardiometabolic implications of circadian misalignment, as occurs acutely with jet lag and chronically with shift work.


Application of topological resonances in experimental investigation of a Fermi golden rule in microwave networks.
We investigate experimentally a Fermi golden rule in two-edge and five-edge microwave networks with preserved time reversal invariance. A Fermi golden rule gives rates of decay of states obtained by perturbing embedded eigenvalues of graphs and networks. We show that the embedded eigenvalues are connected with the topological resonances of the analyzed systems and we find the trajectories of the topological resonances on the complex plane.


Age and Medicare Insurance are Barriers to Telemedicine Access-A Quality Improvement Project.
Telehealth use has had widespread expansion and adoption over the past two years. This study aims to evaluate access to telehealth essentials (TE) using a novel metric. This single institute study surveyed outpatient surgical patients to determine their access to TE. Generalized linear mixed models were used to determine the relationship of demographic and county-level variables on access to four TE. 138 patients were surveyed. Sixty-six (47.8%) were from Appalachian Kentucky. In the survey cohort, 122 (88.4%) had smart phones, 109 (80.7%) had devices with video messaging capabilities, 106 (80.9%) had cellular reception, and 112 (82.4%) had access to WiFi. Increasing age and Medicare insurance were the most consistent predictors of lack of access to TE. Rural Appalachian Kentucky has access to TE. Telehealth has the potential to decrease the healthcare inequity in rural populations, but incompletely address this inequity for the aging population.


Oral intake of Boesenbergia pandurata extract improves skin hydration, gloss, and wrinkling: A randomized, double-blind, and placebo-controlled study.
Photoaging is a severe skin damage that occurs as a result of exposure to external elements, primarily ultraviolet (UV) irradiation. Chronically, UV-irradiated skin exhibits the signs of sunburn and hyperpigmentation with the destruction of connective tissues. Previously, Boesenbergia pandurata (B. pandurata) and its active compound panduratin A showed antiphotoaging activities in vitro and in vivo. The aim of this study was to investigate the clinical efficacy of B. pandurata intake on skin hydration, gloss, wrinkling, and elasticity. A double-blind, placebo-controlled trial was conducted to clinically evaluate the effect of B. pandurata ethanol extract (BPE) containing 8% of panduratin A on human skin hydration, gloss, wrinkling, and elasticity. Ninety-two subjects were randomly assigned to receive tablets containing either BPE or placebo for 12 weeks. The test group had significantly increased skin hydration and gloss and decreased wrinkling compared to the placebo group at 12 weeks. There was no significant difference in skin elasticity between the two groups; however, the increment rate in the test group was higher than that in the placebo group at 12 weeks. None of the subjects developed adverse symptoms during the study period. These results suggest that BPE can be used as a nutraceutical or nutricosmetic material for improving human skin hydration, gloss, and wrinkling.


Periop 101: Improving Perioperative Nursing Knowledge and Competence in Labor and Delivery Nurses Through an Evidence-Based Education and Training Program.
To reach the highest levels of health care quality, all nurses providing intraoperative care to surgical patients should have a firm grasp of the complex knowledge, skills, and guidelines undergirding the perioperative nursing profession. In military treatment facilities, either perioperative registered nurses or labor and delivery (L&D) nurses provide skilled intraoperative nursing care for cesarean deliveries. However, L&D and perioperative nurses occupy vastly different roles in the continuum of care and may possess widely differing levels of surgical training and experience. The purpose of this project was to improve surgical care quality by standardizing and strengthening L&D nurse perioperative training, knowledge, and competence. Our population, intervention, comparative, and outcome question was, "For labor and delivery nurses of a regional military medical center (P), does implementing an evidence-based training program (I), as compared to current institutional nursing practices (C), increase nursing knowledge and perioperative nursing competence (O)?" We implemented Periop 101: A Core Curriculum-Cesarean Section training for 17 L&D nurses, measured knowledge using product-provided testing, and assessed competence using the Perceived Perioperative Competence Scale-Revised. We found that perioperative nursing knowledge and competence significantly improved and were less varied among the nurses after completing the training program. Nurses demonstrated the greatest knowledge area improvements in scrubbing, gowning, and gloving; wound healing; and sterilization and disinfection, for which median scores improved by more than 100%. Nurses reported significantly greater perceived competence across all six domains of the Perioperative Competence Scale-Revised, with the largest improvements realized in foundational skills and knowledge, leadership, and proficiency. We recommend that health care leaders develop policies to standardize perioperative education, training, and utilization for nurses providing intraoperative care to reduce clinician role ambiguity, decrease inefficiencies, and enhance care.


Method development for the enantiomeric purity determination of low concentrations of adrenaline in local anaesthetic solutions by capillary electrophoresis.
L-adrenaline is often included in local anaesthetic (LA) solutions for injection to improve the quality of the anaesthetic block. The concentration of the LA is between 2.5 and 20 mg/ml and the concentration of adrenaline is typically < or = 0.1% of the LA concentration. In order to follow the racemization into d-adrenaline, not only is chiral separation needed but also sufficient resolution from the LA and other components of the injection solution. Furthermore, very high sensitivity is needed in order to be able to determine the d-enantiomer at very low concentrations, i.e. down to about 0.1 microg/ml. The development of a chiral capillary electrophoresis method that is able to determine the racemization of adrenaline is described, together with a limited validation. Samples are injected without pretreatment and analysed with a capillary electrophoresis buffer containing 40 mM heptakis(2,6-di-O-methyl)-beta-cyclodextrin, 0.10 M phosphoric acid and 0.05 M triethanolamine. The amounts of d-adrenaline found in the LA products tested were typically < 3% of the l-adrenaline concentration and < 0.003% of the LA concentration.


Editorial Commentary: Osteochondral Allografting Is a "Kid-Friendly" Cartilage Repair Procedure.
Fresh osteochondral allograft transplantation has been my preferred procedure for chondral and osteochondral lesions for many decades. This is particularly true for patients younger than 18 years of age, where diagnoses such as osteochondritis dissecans, osteochondral fractures, and osteonecrosis predominate, rendering the situation as much a "bone problem" as a "cartilage problem." In the universe of cartilage-repair techniques, osteochondral allografts are particularly useful when bone defects must be managed. Furthermore, allografts have stood the test of time for safety, efficacy, and durability, even in a young, active population. For me, I don't think twice about using fresh allografts in young patients. I might even have to admit that an osteochondral allograft transplantation procedure for an osteochondritis dissecans lesion in a patient younger than 18 years old is my favorite surgery!


Molecular population studies of Simulium damnosum s.l. (Diptera: Simuliidae) using a novel interspersed repetitive DNA marker.
Simulium damnosum s.l., the vector of West African onchocerciasis, has been the target of a major insect control initiative for the past 20 years. However, attempts to study the migration patterns of reinvading infective flies into controlled areas have been restricted by the lack of suitable genetic markers. Here, the results of the first population-level study of S. damnosum s.l. using a repetitive DNA marker, pSO11, are presented. Sequence analysis of pSO11 revealed a complex internal pattern of repetition and an open reading frame with 56.8 per cent similarity to a mouse retrotransposon protein. Combined with an interspersed genomic distribution, the internal structure of pSO11 suggested that it represents the 5' half of a transposable element. The genomic diversity of the sequence was analysed using Southern blot analysis of genomic DNA. Data were collected from 475 individuals from the island of Bioko (in Equatorial Guinea), Cameroon, Côte d'Ivoire and Sierra Leone. The results indicate that pSO11 is useful as an indicator of genomic diversity and that the experimental design used here permits comparison of an approximately random sample of chromosomal loci. Making this assumption, estimates of homozygosity based on pSO11 diversity were used to study inter- and intraspecific variability. The results indicate that pSO11 is potentially useful for studying population-level processes in S. damnosum s.l.


Life events and low birthweight--analysis by infants preterm and small for gestational age.
Social stress was assessed in 92 women with low-birthweight babies and 92 controls using the detailed LEDS measure of life events and severe chronic difficulties. The low-birthweight group was divided into preterm delivery (n = 40), small for gestational age (SGA) (n = 40) and mixed groups. Multivariate analysis was performed using a binomial-logit model to examine whether social factors were independently and significantly associated with low birthweight once the effect of demographic factors, obstetric factors and smoking/drinking were taken into account. Comparison of preterm births with controls indicated that three factors were significantly associated: a previous low-birthweight baby, severe life event/difficulty and bleeding during pregnancy. For SGA babies the factors were: previous low-birthweight baby, low social support and smoking. By using a reliable measure of life events and adequate numbers of low-birthweight babies, this study overcame the potential inaccuracies of previous studies and indicates a more specific relation between social stress and low birthweight.


Glial proliferation in the irradiated rat spinal cord.
The identity of mitotic cells in the ventral half of the irradiated spinal cord in 13-day-old rats was studied by light and electron microscopy. At this post-irradiation interval, astrocytes as well as oligodendrocytes are markedly reduced in both gray and white matter, and few myelin sheaths are present. Earlier studies showed incorporation of 3H-thymidine into cells identified light-microscopically as neuroglia. In the present study, a number of mitotic cells were identified in thick plastic sections. When adjacent thin sections were examined by electron microscopy, these mitotic cells were identified ultrastructurally as astroglia on the basis of the bundles of filaments in their cytoplasm and the irregular outline of the cell body and its processes. It is apparent from this study that astroglia proliferate prior to the delayed myelination that occurs later in the glial cell deprived ventral irradiated cord.


Telomere Length Increase in HIV/HCV-Coinfected Patients with Cirrhosis after HCV Eradication with Direct-Acting Antivirals.
Human immunodeficiency virus (HIV) infection and cirrhosis are associated with a senescent phenotype that decreases telomere length. We evaluated the impact of hepatitis C virus (HCV) elimination on telomere length in patients with advanced HCV-related cirrhosis after sustained virological response (SVR), with all-oral direct-acting antiviral agents (DAAs). Prospective study of 60 HIV/HCV-coinfected and 30 HCV-monoinfected patients with advanced HCV cirrhosis (liver decompensation or liver stiffness measurement (LSM) ≥ 25 kPa, hepatic liver pressure gradient (HVPG) ≥ 10 mmHg, or Child-Pugh-Turcotte (CPT) ≥ 7). The relative telomere length (RTL) was quantified by real-time multiplex PCR (MMqPCR) on peripheral blood mononuclear cells at baseline and 48 weeks after HCV treatment. Generalized linear models (GLMs) adjusted for the most relevant clinical and epidemiological variables and mixed GLMs were used. In comparison with HCV-monoinfected patients, HIV/HCV-coinfected patients were younger (p < 0.001), had lower body mass index (BMI) (p = 0.002), and had been exposed less frequently to interferons (p = 0.011). In addition, they were more frequently men (p = 0.011), smokers (p = 0.005), prior intravenous drug users (IVDUs) (p < 0.001), and alcohol abusers (p = 0.005). RTL was significantly lower in HIV/HCV-coinfected patients than in HCV-monoinfected patients, both at baseline (p < 0.001), and at the end of follow-up (p = 0.032). A significant RTL increase over time was found only for HIV/HCV-coinfected patients (p < 0.001), especially in those patients with compensated cirrhosis (p < 0.001). HCV eradication with all-oral DAAs was associated with an increase in telomere length in HIV/HCV-coinfected patients with advanced cirrhosis, particularly in compensated patients. This finding suggests that HCV clearance may have implications in age-related conditions in this population group.


Predicting the evolution of number of native contacts of a small protein by using deep learning approach.
Native contacts (NCs) are one of the most vital parameters in order to define the resemblance of a protein conformation with its native state. Prediction of number of native contacts in a protein is useful in protein folding mechanism. In this work, we focused to predict the time series of the number of NCs of a small protein, insulin monomer by using three neural network based models, namely; Multi-Layer Perceptron (MLP), Long Short Term Memory (LSTM) and Gated Recurrent Unit (GRU). The input data used in the study was the time evolution of NC values of the folded and unfolded protein conformations computed from the equilibrated trajectories of atomistic molecular dynamics (MD) simulations performed with the aqueous solution of the protein at ambient as well as at an elevated temperature. The evolutionary prediction accuracy of the three models was tested by calculating two error parameters; Root Mean Square Error (RMSE) and Mean Absolute Error (MAE). Our study revealed that, although these three models are successful in forecasting the time evolutions of the NCs in terms of lower RMSE and MAE, the prediction through static memoryless artificial neural network, MLP was relatively less precise as compared to other two recurrent units, LSTM and GRU. The study infers that by using the available input data generated from the MD trajectories; these neural network based models could be used to predict the complex evolution pattern of distanced based structural parameters of a protein with a satisfactory level.


The oxygen radical generator pyrogallol impairs cardiomyocyte contractile function via a superoxide and p38 MAP kinase-dependent pathway: protection by anisodamine and tetramethylpyrazine.
Oxygen-derived free radicals have been demonstrated to contribute to the pathogenesis of myocardial dysfunction, although the underlying mechanism remains not fully understood. This study was designed to examine the role of the superoxide generator pyrogallol on cardiac contractile function and possible intervention with herbal medicines anisodamine and tetramethylpyrazine (TMP) on pyrogallol-induced cardiac contractile response. Adult rat ventricular myocytes were isolated and stimulated to contract at 0.5 Hz. Mechanical properties were evaluated using an IonOptix system including peak shortening (PS), time-to-PS (TPS), time-to-90% relengthening (TR(90)), and maximal velocity of shortening/relengthening (+/-dL/dt). A 10-min exposure of pyrogallol (0 to 10(-2) M) did not affect cardiac contractile mechanics. However, longer duration of pyrogallol exposure (1, 3, and 6 h) significantly shortened resting cell length, reduced PS and +/-dL/dt, and prolonged TPS and TR90 in time- and concentration-dependent manners. The pyrogallol (10(-4) M with 6-h incubation)-induced mechanical defects were prevented by the p38 mitogen-activated protein (MAP) kinase inhibitor SB203580 (1 microM) and superoxide dismutase (SOD, 500 U/mL) with the exception that pyrogallol-induced PS depression was unaffected by SOD. Interestingly, incubation of herbal antioxidants anisodamine (10(-7) M) and TMP (10(-7) M) effectively attenuated the pyrogallol-induced cardiac mechanical defects with the exception of PS unaffected by TMP. Our data demonstrate a direct inhibitory effect of pyrogallol on cardiac contraction, probably in a superoxide- and p38 MAP kinase-dependent manner. The antioxidant medicines anisodamine and TMP may be useful in the treatment of oxygen free radical-induced myocardial dysfunction.


Creatine uptake regulates CD8 T cell antitumor immunity.
T cells demand massive energy to combat cancer; however, the metabolic regulators controlling antitumor T cell immunity have just begun to be unveiled. When studying nutrient usage of tumor-infiltrating immune cells in mice, we detected a sharp increase of the expression of a CrT (Slc6a8) gene, which encodes a surface transporter controlling the uptake of creatine into a cell. Using CrT knockout mice, we showed that creatine uptake deficiency severely impaired antitumor T cell immunity. Supplementing creatine to WT mice significantly suppressed tumor growth in multiple mouse tumor models, and the combination of creatine supplementation with a PD-1/PD-L1 blockade treatment showed synergistic tumor suppression efficacy. We further demonstrated that creatine acts as a "molecular battery" conserving bioenergy to power T cell activities. Therefore, our results have identified creatine as an important metabolic regulator controlling antitumor T cell immunity, underscoring the potential of creatine supplementation to improve T cell-based cancer immunotherapies.


Acetaminophen overdose.
Acetaminophen is a remarkably safe agent when used in therapeutic doses. Most reported overdoses of acetaminophen are the result of suicide attempts. The clinical course of patients with toxic blood levels follows four distinct stages. Symptoms of nausea, vomiting, diaphoresis, and anorexia usually begin within seven to 14 hours after ingestion. After 24 to 48 hours, these symptoms may diminish, but SGOT, SGPT, bilirubin, and prothrombin time begin to rise. Peak hepatotoxicity occurs at 72 to 96 hours, and SGOT levels of 20,000 I.U. are not unusual. Oral N-acetylcysteine is the drug of choice for acetaminophen overdose. Intravenous use of N-acetylcysteine is advocated in England, Europe, and elsewhere, but it is not available in the United States. Clinical studies of oral and intravenous N-acetylcysteine clearly demonstrate that the drug has a profound effect on reducing morbidity and mortality if it is administered during the first 16 hours after the overdose. In addition, data from these studies have shown that alcohol taken simultaneously with an overdose of acetaminophen is actually hepatoprotective. Therefore, patients who have consumed alcohol at the time of overdose, or those who are chronic alcoholics, should be managed in the same way as patients with no exposure to alcohol. However, study results also reveal that overdose in children under 10 to 12 years of age follows a distinctly different pattern. These children demonstrate a lesser degree of hepatotoxicity and have only minor increases in transaminase levels.


Blastula stage specification of avian neural crest.
Cell fate specification defines the earliest steps towards a distinct cell lineage. Neural crest, a multipotent stem cell population, is thought to be specified from the ectoderm, but its varied contributions defy canons of segregation potential and challenges its embryonic origin. Aiming to resolve this conflict, we have assayed the earliest specification of neural crest using blastula stage chick embryos. Specification assays on isolated chick epiblast explants identify an intermediate region specified towards the neural crest cell fate. Furthermore, low density culture suggests that the specification of intermediate cells towards the neural crest lineage is independent of contact mediated induction and Wnt-ligand induced signaling, but is, however, dependent on transcriptional activity of β-catenin. Finally, we have validated the regional identity of the intermediate region towards the neural crest cell fate using fate map studies. Our results suggest a model of neural crest specification within a restricted epiblast region in blastula stage chick embryos.


Safety and Feasibility of Subcutaneous Purse-String Suture of the Femoral Vein After Electrophysiological Procedures on Uninterrupted Oral Anticoagulation.
The aim of this study was to compare safety and feasibility of a subcutaneous purse-string suture (PSS) with manual compression (MC) to gain hemostasis in patients after multiple femoral venous punctures undergoing electrophysiological procedures on uninterrupted oral anticoagulation (OAK). A total of 784 patients who underwent catheter ablation for atrial fibrillation (n = 564) or (a)typical atrial flutter (n = 220) were assessed. Four hundred sixty-two patients received PSS (58.9%) and 322 patients (41.1%) received MC to gain hemostasis. All patients were on uninterrupted full-dose OAK. During the procedure, weight-adapted heparin was applied. Venous sheath diameter were 8Fr (n = 2)/11.5Fr (n = 1) for left atrial or 8Fr (n = 1)/6Fr (n = 2) for right atrial procedures. No protamine was administered at the end of the procedure. After PSS, patients' had 6 hours of bed rest compared with 10 hours after MC (sheath removal after 4 hours followed by a bandage for 6 hours). PSS was removed the following day. All patients underwent duplex sonography of the access site the following day. Using the PSS, hemostasis was achieved in 453 of 462 patients (98%). MC leads to hemostasis in all 322 patients. No difference was found between the 2 approaches regarding hematomas (<5 cm or >5 cm), arterio-venous fistulas, or pseudoaneurysms. No major complication such as ipsilateral leg ischemia, the need of vascular surgery, or deep vein thrombosis occurred. In conclusion, PSS is a safe and effective way to gain immediate hemostasis after multiple punctures of the femoral vein in patients undergoing catheter ablation on OAK. PSS avoids MC and leads to shorter patient immobilization.


[Burning mouth syndrome].
Burning sensation of the tongue is a common complaint. In some patients this is diagnosed as Burning Mouth Syndrome (BMS). The prevalence of BMS is 0.8-19% of the general population. The typical complaint is localized to the anterior part of the tongue and may be accompanied by dry mouth sensation or taste disorder. The differential diagnosis of BMS is based on the specific details of the complaint, the clinical findings and laboratory results. The patients population consists of mainly post-menopausal women, even though it can appear in younger patients of both genders. The pathogenesis is only partially identified. There are different treatment approaches.


Arabidopsis PLDζ1 and PLDζ2 localize to post-Golgi membrane compartments in a partially overlapping manner.
Arabidopsis PLDζ1 and PLDζ2 localize to the trans-Golgi network and to compartments including the trans-Golgi network, multi-vesicular bodies, and the tonoplast, respectively, depending on their N-terminal regions containing PX-PH domains. Phospholipase D (PLD) is involved in dynamic cellular processes, including membrane trafficking, cytoskeletal reorganization, and signal transduction for gene expression, through the production of phosphatidic acid in membrane compartments specific to each process. Although PLD plays crucial roles in various plant phenomena, the underlying processes involving PLD for each phenomenon remain largely elusive, partly because the subcellular localization of PLD remains obscure. In this study, we performed comparative subcellular localization analyses of the Arabidopsis thaliana PX-PH-PLDs PLDζ1 and PLDζ2. In mature lateral root cap cells, own promoter-driven fluorescence protein fusions of PLDζ1 localized to the entire trans-Golgi network (TGN) while that of PLDζ2 localized to punctate structures including part of the TGN and multi-vesicular bodies as well as the tonoplast. These localization patterns were reproduced using N-terminal partial proteins, which contain PX-PH domains. An inducibly overexpressed fluorescence protein fusion of the PLDζ2 partial protein first localized to punctate structures, and then accumulated predominantly on the tonoplast. Further domain dissection analysis revealed that the N-terminal moiety preceding the PX-PH domain of PLDζ2 was required for the tonoplast-predominant accumulation. These findings suggest that PLDζ1 and PLDζ2 play partially overlapping but nonetheless distinctive roles in post-Golgi compartments along the membrane trafficking pathway from the TGN to the tonoplast.


Improving Family Communication.
TeenSmart International harnesses the power and flexibility of technology to empower youth to take personal responsibility for their health and lifestyle choices. Access to the Internet via mobile phones is often cheaper than paying to connect to a wired broadband service, and in rural areas, mobile networks may be the only means of accessing the Internet. This study assessed the feasibility, acceptability, and impact of "cues to action" or brief motivating cell phone text messages to improve adolescent family communication and relationships. A quasi-experimental design using a voluntary sample of 100 Nicaraguan youth at high risk for poor family communication participated. Pre- and posttest quantitative measures using Student t statistical analysis, a focus group, and a participant testimony provided the evaluation evidence. Findings suggest that there are economic and motivational barriers to the use of text messages, but when barriers are eliminated, the behavioral results are positive. Youth who received two weekly text messages over a 6-month period demonstrated statistically significant improvements in family communication perceptions, attitudes, and behaviors, strengthening their family communications and relationships. Brief and personalized text messaging "cues to action" may be a cost-effective intervention to improve adolescent healthy lifestyle behaviors.


Parametric survival analysis for gating kinetics of single potassium channels.
The gating mechanism and the role of the S4 region in the activation of Shaker potassium channel was studied by statistical analysis on the wild type and mutant channels which have mutations in the S4 region. Single channel currents were recorded with the patch-clamp technique. The first latency time was analyzed with a parametric survival time regression model in which the generalized gamma distribution for the error term was assumed. Discrimination among Weibull, gamma, log-normal and exponential distributions was done with the likelihood ratio test. The three-parameter generalized gamma distribution was shown to be appropriate for the data set. The multiple regression function provides the statistical tests and the quantitative descriptions for the relationships between the mutations and the voltage dependence of the gating process. These results on statistical relations support the hypothesis that the S4 region plays an important role in sensing transmembrane voltage in the gating process, but the gating mechanism is not solely accounted for by the electrostatic interaction between the charged amino acids and the transmembrane voltage field. This work demonstrates that the survival analysis procedures can be useful tools for analyzing neurophysiological signals.


Comparison of the canalith repositioning procedure and vestibular habituation training in forty patients with benign paroxysmal positional vertigo.
Forty patients with benign paroxysmal positional vertigo were treated with either the canalith repositioning procedure or vestibular habituation exercises to determine which treatment approach would be most effective. Twenty additional patients with benign paroxysmal positional vertigo were not treated and served as a control group. The intensity and duration of symptoms were monitored during a 3-month period. All patients had symptomatic relief in the treated groups. The canalith repositioning procedure seemed to give resolution of symptoms with fewer treatments, but long-term results show either treatment approach is effective in relieving positional vertigo. A significant number of patients in the control group (75%) continued to have vertigo. Advantages and disadvantages of the canalith repositioning procedure and vestibular habituation exercises are discussed.


C-Kit Positive Cardiac Stem Cells and Bone Marrow-Derived Mesenchymal Stem Cells Synergistically Enhance Angiogenesis and Improve Cardiac Function After Myocardial Infarction in a Paracrine Manner.
Stem cell transplantation offers a promising treatment for heart failure. Recent studies show that both c-kit positive cardiac stem cells (CSCs) and bone marrow-derived mesenchymal stem cells (BM-MSCs) are good candidates for stem cell therapy to treat heart failure; however, the exact mechanism of stem cell therapy in improving cardiac function of ischemic cardiomyopathy is not fully known. Our objective was to test our hypothesis that CSCs and/or BM-MSCs repair the damaged heart by boosting post-myocardial infarction (MI) angiogenesis in a paracrine manner. We isolated and purified CSCs and BM-MSCs from rats. Intramyocardial injections of CSCs and/or BM-MSCs were performed at 28 days after MI. We applied cardiac ultrasound and histological analysis to evaluate the effect of cell therapy on cardiac function and cardiac remodeling. In vivo donor cell transplantation experiments showed that CSCs and/or BM-MSCs improved cardiac function after MI and reduced infarct size. However, in vivo cell tracking experiments showed that minimal donor cells remained in the myocardium after cell transplantation. Our further in vitro and in vivo experiments showed that transplantation of CSCs enhanced the expression of pro-angiogenic factors and boosted post-MI angiogenesis in the myocardium in a paracrine manner, which in part contributed to the effect of CSCs on cardiac recovery after MI. CSCs and BM-MSCs synergistically inhibited CSC/BM-MSC apoptosis and enhanced their proliferation in a paracrine manner. This resulted in a larger number of transplanted cells remaining in the post-MI myocardium after coinjection of CSCs and BM-MSCs, and therefore the accumulation of more pro-angiogenic factors in the heart tissue compared to transplantation of CSCs or MSCs alone. Consequently, transplantation of both CSCs and BM-MSCs was superior to transplantation of either CSCs or BM-MSCs alone to boost post-MI angiogenesis and improve cardiac function after MI. C-kit+ CSC and/or BM-MSC transplantation can improve cardiac function after MI in a paracrine manner. Coinjection of both CSCs and BM-MSCs improves cardiac function more significantly than CSC or BM-MSC transplantation alone in a paracrine manner by improving the engraftment of donor cells and boosting the expression of multiple pro-angiogenic factors.


Hepatitis A outbreak in a residential school.
Outbreaks of hepatitis A occurred sequentially in two wards for children in a residential institution for the mentally retarded in Sydney. Twenty-six of 41 children were initially susceptible to hepatitis A. In the first ward affected, 11 of 13 susceptible children (85%), and in the second ward, four of 13 susceptibles (31%), were infected. Of the 15 showing serological evidence of infection, five (33%) were clinically jaundiced.


Live, die, or regenerate? New insights from multi-omic analyses.
In this issue of Neuron, three studies establish new strategies to uncover mediators of retinal neuroprotection and optic nerve regeneration. Tian et al. (2022) carry out a multi-omics screen and identify transcriptional regulators of axon injury signaling leading to cell death; Jacobi et al. (2022) and Li et al. (2022) combine retrograde tracing and single-cell RNA-seq (scRNA-seq) to uncover molecular targets for axon regeneration.


Isolation of the glucose oxidase gene from Talaromyces flavus and characterisation of its role in the biocontrol of Verticillium dahliae.
The glucose oxidase gene from the biocontrol fungus Talaromyces flavus has been isolated and shown to be only 64% identical at the amino-acid sequence level to the similar enzyme from Aspergillus niger. A transformation system has been developed for both T. flavus and the related T. macrosporus and has been used to create Talaromyces spp. which either over-express or are deficient in glucose oxidase. In vitro inhibition experiments on Verticillium dahliae using culture filtrates from these transformants indicates that secreted glucose oxidase is responsible for a large part of the growth inhibition of V. dahliae microsclerotia and hyphae by T. flavus, although other inhibitory compounds may also play a role. In pot trials with cotton plants, both Talaromyces species had some biocontrol activity, but there was no significant difference in the incidence of Verticillium wilt with either the presence or absence of glucose oxidase activity in the biocontrol fungus. Under the experimental conditions used, insufficient glucose is presumably present in the soil around cotton roots to generate sufficient hydrogen peroxide to inhibit V. dahliae and the observed biocontrol activity must be attributed to other factors.


The pursuit of happiness measurement: a psychometric model based on psychophysiological correlates.
Everyone is interested in the pursuit of happiness, but the real problem for the researchers is how to measure it. Our aim was to deeply investigate happiness measurement through biomedical signals, using psychophysiological methods to objectify the happiness experiences measurements. The classic valence-arousal model of affective states to study happiness has been extensively used in psychophysiology. However, really few studies considered a real combination of these two dimensions and no study further investigated multidimensional models. More, most studies focused mainly on self-report to measure happiness and a deeper psychophysiological investigation on the dimensions of such an experience is still missing. A multidimensional model of happiness is presented and both the dimensions and the measures extracted within each dimension are comprehensively explained. This multidimensional model aims at being a milestone for future systematic study on psychophysiology of happiness and affective states.


Self-efficacy for managing pain, symptoms, and function in patients with lung cancer and their informal caregivers: associations with symptoms and distress.
This study examined self-efficacy for managing pain, symptoms, and function in patients with lung cancer and their caregivers, and associations between self-efficacy and patient and caregiver adjustment. One hundred and fifty-two patients with early stage lung cancer completed measures of self-efficacy, pain, fatigue, quality of life, depression, and anxiety. Their caregivers completed a measure assessing their self-efficacy for helping the patient manage symptoms and measures of psychological distress and caregiver strain. Analyses indicated that, overall, patients and caregivers were relatively low in self-efficacy for managing pain, symptoms, and function, and that there were significant associations between self-efficacy and adjustment. Patients low in self-efficacy reported significantly higher levels of pain, fatigue, lung cancer symptoms, depression, and anxiety, and significantly worse physical and functional well being, as did patients whose caregivers were low in self-efficacy. When patients and caregivers both had low self-efficacy, patients reported higher levels of anxiety and poorer quality of life than when both were high in self-efficacy. There were also significant associations between patient and caregiver self-efficacy and caregiver adjustment, with lower levels of self-efficacy associated with higher levels of caregiver strain and psychological distress. These preliminary findings raise the possibility that patient and caregiver self-efficacy for managing pain, symptoms, and function may be important factors affecting adjustment, and that interventions targeted at increasing self-efficacy may be useful in this population.


Coupled heating/acidification pretreatment of chemical sludge for dewatering by using waste sulfuric acid at low temperature.
A cost-effective approach for pretreatment of chemical sludge for further dewatering, based on the idea of "using waste to treat waste", is provided. It is a coupled heating/acidification pretreatment method, where waste sulfuric acid is employed and relatively low temperatures (<100 °C) are applied. Effects of reaction time, temperature, and dosage of waste acid on dewatering performance (both dewatering speed and degree) are studied. Under the optimal conditions (reaction time: 30 min; temperature: 90 °C; waste acid dosage: 0.175 g/(g dried sludge)), the method of this work demonstrates three advantages compared to the conventional method using lime+polyacrylamide: lower moisture content of treated sludge; higher calorific value for incineration process; and lower cost. Detailed mechanism of the pretreatment for dewatering is investigated via characterizations and statistical analyses of various parameters, among which zeta potential, particle size, protein and polysaccharide contents, soluble chemical oxygen demand (SCOD), reduction of combined water and volatile suspended solid (VSS), are associated with dewatering performance. Both heating and acidification generate disintegration of cells in sludge, giving rise to two phenomena: more organic matters are released into solution and more bound water turns into free water. Meantime, the released organic polymers flocculate sludge particles, further accelerating the solid-liquid separation process.


Impact of long-term ethanol consumption on CYP1A2 activity.
Ethanol is a well-known inducer of CYP2E1; whether or not it is an inducer of other cytochromes has not been investigated systematically. The aim of our study was to evaluate the impact of ethanol consumption on the activity of CYP1A2, which has been shown to be influenced by drugs (inhibited or induced). We evaluated CYP1A2 activity by the ratio of the molar urinary concentrations of the three end products of paraxanthine demethylation of caffeine to the molar concentration of a paraxanthine 8-hydroxylation product. This urinary metabolite ratio has previously been shown to correlate with caffeine clearance. The caffeine metabolites were measured in urine collected during the 3 hours after oral administration of 200 mg caffeine. The caffeine test was performed in 12 smokers (> 25 cigarettes/day) and 12 nonsmokers, all of whom were alcoholic inpatients (daily intake > 100 mg absolute ethanol), within the first 3 days of their hospital stay and after 14 days of abstinence from ethanol. In alcoholic patients who were smokers the molar urinary concentration ratio was 3.14 +/- 0.97 before withdrawal and 4.01 +/- 0.92 after 14 days of abstinence from ethanol. In contrast, in alcoholic patients who were nonsmokers it was 2.62 +/- 0.95 and 2.18 +/- 0.96 before and after withdrawal, respectively. In volunteers who were smokers the molar urinary concentration ratio was 5.02 +/- 1.51, whereas in volunteers who were nonsmokers it was 3.22 +/- 1.46. Our results confirm the well-known induction of CYP1A2 activity by tobacco smoking and show that this induction is masked by long-term ethanol consumption.


Hemophilus parainfluenzae prostatitis in a homosexual man with chronic lymphadenopathy syndrome and HTLV-III infection.
Hemophilus parainfluenzae, a common upper respiratory tract pathogen, has been reported to cause pharyngitis, epiglottitis, otitis media, conjunctivitis, and pneumonia. Rarely H. parainfluenzae infects the urinary tract, and is believed not to have been previously reported as a cause of prostatitis. A case of H. parainfluenzae in a young homosexual man infected with HTLV-III and chronic lymphadenopathy is described. Common clinical syndromes such as prostatitis may be associated with unusual pathogens in persons immunodeficient due to HTLV-III infection.


Photoelectrochemical immunoassay of interleukin-6 based on covalent reaction-triggered photocurrent polarity switching of ZnO@fullerenol.
We report here a novel photocurrent polarity switching strategy for a photoelectrochemical immunoassay driven by the covalent reaction between fullerenol (COH) and chloranilic acid (CA). The sensitive detection of interleukin-6 is achieved by using CA-encapsulated liposome as the label and COH-coated ZnO as the photoactive material, with a detection limit of 1.0 fg mL-1.


In vivo two-photon imaging of T cell motility in joint-draining lymph nodes in a mouse model of rheumatoid arthritis.
Recent imaging studies on intact lymph nodes (LNs) of naïve T cell receptor (TCR)-transgenic mice have reported that T cells reduce their motility upon contact with relevant antigen-presenting cells (APCs). Using in vivo two-photon imaging of T cells in joint-draining (JD) LNs, we examined whether similar changes in T cell motility are observed in wild type mice. Co-transfer of T cells from naïve mice and antigen-experienced T cells from mice with proteoglycan (PG)-induced arthritis into naïve or arthritic recipients resulted in prolonged interactions of antigen-experienced T cells with APCs upon intra-articular antigen (PG) injection, indicating that T cells from arthritic wild type mice recapitulate the motile behavior reported in naïve TCR-transgenic mice. However, naïve T cells also engaged in stable interactions with APCs in the JDLNs of arthritic recipients, suggesting an enhanced ability of APCs in the JDLNs of arthritic hosts to present antigen to either naïve or antigen-experienced T cells.


Opportunities and tradeoffs in single-cell transcriptomic technologies.
Recent technological and algorithmic advances enable single-cell transcriptomic analysis with remarkable depth and breadth. Nonetheless, a persistent challenge is the compromise between the ability to profile high numbers of cells and the achievement of full-length transcript coverage. Currently, the field is progressing and developing new and creative solutions that improve cellular throughput, gene detection sensitivity and full-length transcript capture. Furthermore, long-read sequencing approaches for single-cell transcripts are breaking frontiers that have previously blocked full transcriptome characterization. We here present a comprehensive overview of available options for single-cell transcriptome profiling, highlighting the key advantages and disadvantages of each approach.


The role of echocardiography in the evaluation and management of aortic stenosis in the older adult.
Aortic stenosis is currently the most predominant valvular pathology in older adults. Signs and symptoms of aortic stenosis in this age-group may be difficult to recognize due to the decreased activity associated with aging and attribution of symptoms to other conditions. Echocardiography can be very helpful in the assessment of valvular structure and real time hemodynamic evaluation as well as in the progression of the disease over time. Unprecedented advances in echocardiography, including real time three-dimensional echocardiography, facilitate a comprehensive assessment of this condition and help in the decision-making process. Recent innovations in the percutaneous treatment of valvular diseases promise a revolution in the treatment of aortic stenosis especially in older adults.


Assessment of dust trace elements in an e-waste recycling area and related children's health risks.
Children from Guiyu, an electronic waste (e-waste) recycling town, are exposed to trace elements via dust. However, the source, pathways, and influence factors of house dust and the association of house dust with child inflammation in an e-waste recycling area are not well-known. This study investigated dust trace elements in children's living environment and the associations of house dust trace elements with influence factors and child inflammation. A total of 108 dust samples from children's residences, roads, and kindergartens in Guiyu (an exposed area) and Haojiang and Shantou urban areas (reference areas) were collected and analyzed, as well as children's questionnaire data. The Mann-Whitney U test found there were higher trace element concentrations in road dust (Co, Ni, and Cu), kindergarten dust (Al, V, Mn, Co, Ni, and Zn), and house dust (V, Co, Cu, As, and Cd) in Guiyu than in Haojiang and Shantou urban areas (P < 0.05). Our analysis showed that house dust and road dust have similar distribution patterns of trace elements. Spearman's correlations showed close relationships among quantities of trace elements (P < 0.05). Higher trace element concentrations in dust were found in houses that used indoor shoe cabinets and opened windows frequently (P < 0.05). In houses of children with airway inflammation, higher dust Ba concentrations were found (P < 0.05), and if their fathers did not work with e-waste, we found higher dust Pb concentrations (Mann-Whitney U test, P < 0.05). Health assessments showed a high risk of exposure through ingestion and an acceptable risk of exposure through inhalation of dust trace elements for children. However, relationships between airway inflammation and house dust trace elements showed the inhalation risk might be underestimated. This study suggests trace element exposure via dust poses a health risk for children living in e-waste recycling areas.


GnRH pulse frequency differentially regulates steroidogenic factor 1 (SF1), dosage-sensitive sex reversal-AHC critical region on the X chromosome gene 1 (DAX1), and serum response factor (SRF): potential mechanism for GnRH pulse frequency regulation of LH beta transcription in the rat.
The issue of how rapid frequency GnRH pulses selectively stimulate LH transcription is not fully understood. The rat LHβ promoter contains two GnRH-responsive regions: the proximal region has binding elements for SF1, and the distal site contains a CArG box, which binds SRF. This study determined whether GnRH stimulates pituitary SF1, DAX1 (an endogenous SF1 inhibitor), and SRF transcription in vivo, and whether regulation is frequency dependent. Male rats were pulsed with 25 ng GnRH i.v. every 30 min or every 240 min for 1-24 h, and primary transcripts (PTs) and mRNAs were measured by real time PCR. Fast frequency GnRH pulses (every 30 min) increased SF1 PT (threefold) within 1 h, and then declined after 6 h. SF1 mRNA also increased within 1 h and remained elevated through 24 h. Fast frequency GnRH also stimulated a transient increase in DAX1 PT (twofold after 1 h) and mRNA (1.7-fold after 6 h), while SRF mRNA rose briefly at 1 h. Slow frequency pulses did not affect gene expression of SF1, DAX1, or SRF. These findings support a mechanistic link between SF1 in the frequency regulation of LHβ transcription by pulsatile GnRH.


Effect of glucagon infusion on plasma cyclic AMP in patients with cholestatic hepatitis and obstructive jaundice. New test of hepatic cholestasis.
Plasma cyclic AMP concentration during glucagon infusion at various time intervals was determined in 8 normal subjects, 9 patients with extrahepatic obstructive jaundice and 10 patients with cholestatic hepatitis (hepatitis A and B). Plasma cyclic AMP concentrations (pmol/ml) during glucagon infusion in patients with both obstructive jaundice and cholestatic hepatitis were found to be greater than those in control subjects. In addition, a significant difference in plasma cyclic AMP concentrations was found between patients with cholestatic hepatitis and obstructive jaundice at the 10th minute of glucagon infusion. These results indicate that plasma cyclic AMP levels at the 10th minute of glucagon infusion represent a reliable diagnostic index of cholestatic jaundice.


Visualisation and biovolume quantification in the characterisation of biofilm formation in Mycoplasma fermentans.
The ability of mycoplasmas to persist on surfaces has been widely acknowledged, despite their fastidious nature. However, the organism's capability to form a recognisable biofilm structure has been identified more recently. In the current study Mycoplasma fermentans was found to adhere to the glass surface forming highly differentiated biofilm structures. The volumes of biofilm microcolonies were quantified and observed to be greater at late growth stage than those at early growth stage. The channel diameters within biofilms were measured with Scanning Electron Microscopy images and found to be consistent with the size observed in Confocal Laser Scanning Microscope images. The combination of imaging methods with 3D visualisation provides key findings that aid understanding of the mycoplasma biofilm formation and true biofilm architecture. The observations reported here provide better understanding of the persistence of these minimalist pathogens in nature and clinical settings.


Experimental modal analysis on fresh-frozen human hemipelvic bones employing a 3D laser vibrometer for the purpose of modal parameter identification.
To provide a close-to-reality simulation model, such as for improved surgery planning, this model has to be experimentally verified. The present article describes the use of a 3D laser vibrometer for determining modal parameters of human pelvic bones that can be used for verifying a finite elements model. Compared to previously used sensors, such as acceleration sensors or strain gauges, the laser vibrometric procedure used here is a non-contact and non-interacting measuring method that allows a high density of measuring points and measurement in a global coordinate system. Relevant modal parameters were extracted from the measured data and provided for verifying the model. The use of the 3D laser vibrometer allowed the establishment of a process chain for experimental examination of the pelvic bones that was optimized with respect to time and effort involved. The transfer functions determined feature good signal quality. Furthermore, a comparison of the results obtained from pairs of pelvic bones showed that repeatable measurements can be obtained with the method used.


Blood-based prognostic biomarkers in Crohn's Disease patients on biologics: a promising tool to predict endoscopic outcomes.
There is a growing need for biomarkers to predict therapeutic outcome in Crohn's disease (CD). The aim was to evaluate whether NLR (neutrophil-to-lymphocyte ratio), PLR (platelet-to-lymphocyte ratio), ELR (eosinophil-to-lymphocyte ratio), and ENLR (eosinophil*neutrophil-to-lymphocyte ratio), could be prognostic biomarkers of endoscopic response (ER) when starting biologics. Patients with CD who started biologics were enrolled. Multivariate analysis was used to evaluate whether NLR, PLR, ELR and ENLR at baseline and at w12 could predict ER (Simple Endoscopic Score for Crohn's disease [SES-CD] ≤2 or SES-CD≤2 and Rutgeerts i0-i1) after 52 weeks of treatment. Area under the curve (AUC) was calculated to find the cutoffs. 107 patients were included. Patients who achieved ER had significantly lower baseline NLR (p = 0.025), ELR (p = 0.013), and ENLR (p = 0.020) compared with those without ER; results after 12 weeks of treatment for ELR (p = 0.006) and ENLR (p = 0.003). AUC was 0.64 (p = 0.003), 0.67 (p = 0.006) and 0.65 (p = 0.014) for NLR, ELR and ENLR. Low NLR, ELR and ENLR can predict ER and could be used in clinical practice for a better management of CD patients.


Marked sympathetic activation and baroreflex dysfunction in true resistant hypertension.
An increase in sympathetic drive to the heart and the peripheral circulation characterizes mild and severe essential hypertension. However, it remains unsettled whether sympathetic cardiovascular influences are potentiated in true resistant hypertension (RHT). In 32 RHT patients treated with 4.6 ± 0.3 drugs (mean ± SEM) and aged 58.6 ± 2.1 years, 35 non-resistant treated hypertensives (HT) and 19 normotensive controls (NT), all age-matched with RHT, we measured clinic, 24-hour ambulatory and beat-to-beat blood pressures (BP), heart rate (HR, EKG), muscle sympathetic nerve traffic (MSNA, microneurography) and spontaneous baroreflex MSNA-sensitivity. BP values were markedly greater in RHT patients than in NT and HT (172.2 ± 1.7/100.7 ± 1.2 vs 132.1 ± 1.3/82.1 ± 0.9 and 135.5 ± 1.2/83.6 ± 0.9 mmHg, P < 0.01). This was paralleled by a significant and marked increase in MSNA (87.8 ± 2.0 vs 46.8 ± 2.6 and 59.3 ± 1.7 and bursts/100 heartbeats, P < 0.01). In multiple regression analysis the MSNA increase observed in RHT was significantly related to hemodynamic, hormonal and metabolic variables. It was also significantly related to plasma aldosterone values as well as spontaneous baroreflex MSNA-sensitivity, which were the variables that at the multivariate analysis were more closely related to the adrenergic activation of RHT after adjustment for confounders, including antihypertensive treatment (r(2)partial=0.04405 and r(2)partial=0.00878, P<0.05 for both). These data represent the first evidence that RHT is a state of marked adrenergic overdrive, greater for magnitude than that detectable in HT. They also suggest that impaired baroreflex mechanisms, along with hemodynamic and neurohumoral factors, may be responsible for the phenomenon.


Localization of the effects of electroconvulsive shock on beta-adrenoceptors in the rat brain.
Chronic (10 days) application of electroconvulsive shock (ECS) to male and female rats results in a significant but highly localized decrease in beta-adrenoceptor number. Saturation studies on homogenized tissue revealed a decrease in Bmax in the frontal cortex and hippocampus but not in caudate or cerebellum of both sexes. Quantitative autoradiographic analysis showed the changes in the hippocampus to be in the CA1 and dentate gyrus but not CA3. No effect was seen in caudate, globus pallidus, substantia nigra, cerebellar molecular and granular layers and several thalamic and hypothalamic nuclei.


Active case detection, treatment of falciparum malaria with combined chloroquine and sulphadoxine/pyrimethamine and vivax malaria with chloroquine and molecular markers of anti-malarial resistance in the Republic of Vanuatu.
Chloroquine-resistant Plasmodium falciparum was first described in the Republic of Vanuatu in the early 1980s. In 1991, the Vanuatu Ministry of Health instituted new treatment guidelines for uncomplicated P. falciparum infection consisting of chloroquine/sulphadoxine-pyrimethamine combination therapy. Chloroquine remains the recommended treatment for Plasmodium vivax. In 2005, cross-sectional blood surveys at 45 sites on Malo Island were conducted and 4,060 adults and children screened for malaria. Of those screened, 203 volunteer study subjects without malaria at the time of screening were followed for 13 weeks to observe peak seasonal incidence of infection. Another 54 subjects with malaria were followed over a 28-day period to determine efficacy of anti-malarial therapy; chloroquine alone for P. vivax and chloroquine/sulphadoxine-pyrimethamine for P. falciparum infections. The overall prevalence of parasitaemia by mass blood screening was 6%, equally divided between P. falciparum and P. vivax. Twenty percent and 23% of participants with patent P. vivax and P. falciparum parasitaemia, respectively, were febrile at the time of screening. In the incidence study cohort, after 2,303 person-weeks of follow-up, the incidence density of malaria was 1.3 cases per person-year with P. vivax predominating. Among individuals participating in the clinical trial, the 28-day chloroquine P. vivax cure rate was 100%. The 28-day chloroquine/sulphadoxine-pyrimethamine P. falciparum cure rate was 97%. The single treatment failure, confirmed by merozoite surface protein-2 genotyping, was classified as a day 28 late parasitological treatment failure. All P. falciparum isolates carried the Thr-76 pfcrt mutant allele and the double Asn-108 + Arg-59 dhfr mutant alleles. Dhps mutant alleles were not detected in the study sample. Peak seasonal malaria prevalence on Malo Island reached hypoendemic levels during the study observation period. The only in vivo malaria drug efficacy trial thus far published from the Republic of Vanuatu showed chloroquine/sulphadoxine-pyrimethamine combination therapy for P. falciparum and chloroquine alone for P. vivax to be highly efficacious. Although the chloroquine-resistant pfcrt allele was present in all P. falciparum isolates, mutant alleles in the dhfr and dhps genes do not yet occur to the extent required to confer sulphadoxine-pyrimethamine resistance in this population.