Inhibitory effects of plant phenols on the activity of selected enzymes.
Selected enzymes (alpha-amylase, trypsin, and lysozyme) were allowed to react with some simple phenolic and related compounds (caffeic acid, chlorogenic acid, ferulic acid, gallic acid, m-, o-, and p-dihydroxybenzenes, quinic acid, and p-benzoquinone). The derivatized enzymes obtained were characterized in terms of their activity. In vitro experiments showed that the enzymatic activity of the derivatives was adversely affected. This enzyme inhibition depended on the reactivity of the phenolic and related substances tested as well as on the kind of substrate applied. The decrease in the activity was accompanied by a reduction in the amount of free amino and thiol groups, as well as tryptophan residues, which resulted from the covalent attachment of the phenolic and related compounds to these reactive nucleophilic sites in the enzymes. The enzyme inhibition correlates well with the blocking of the mentioned amino acid side chains.


Effects of perfusion rate and glucose concentration on glucose absorption in intestinal thiry-vella loop in sheep.
The effects of the perfusion rate and glucose concentration in perfusate on glucose absorption in the intestinal Thiry-Vella loop of conscious sheep were studied. When 10 mM glucose was perfused at the rates of 0.5, 1, 2 and 4 ml/min, the absorption rates were 77.1 +/- 2.2, 54.9 +/- 2.3, 31.6 +/- 2.1 and 12.9 +/- 0.3%, respectively. When 5, 10, 20 and 40 mM glucose solutions were perfused at 1 ml/min, the absorption rates were 75.5 +/- 1.7, 52.2 +/- 2.2, 29.4 +/- 1.9 and 19.5 +/- 0.1%, respectively. We conclude that the perfusion of 10 mM glucose solution at 1 ml/min, in which about a 50% absorption rate was obtained, are the optimal conditions for the study of glucose absorption in the intestinal loop of sheep.


Positive Coombs test in acute leukaemia.
We present the results of the immunohaematological tests performed in an unselected group of patients with acute leukaemia at the time of diagnosis, and when possible the follow-up in remission and/or in relapse. Thirteen out of the 112 patients tested had a positive Coombs test at the time of diagnosis and, in six patients, the Coombs test became positive during remission. All the 19 positive Coombs test were of the complement type with, in 11 cases, an anti-I antibody eluted from the patient's RBC. There was no relationship between the FAB morphologic subtype, the presence of other immune abnormalities, the course of the leukaemia and the immunohaematological abnormalities. Several hypotheses on the possible relationships between the acute leukaemias and the immunohaematological abnormalities are discussed.


Immunological responses to maxillary on-lay allogeneic bone grafts.
4 patients with severely resorbed maxillae underwent rehabilitation with on-lays of allogeneic femoral head bone grafts, titanium implants (Brånemark System) and fixed prostheses. Donors and recipients were matched according to blood groups (ABO/Rh). Potential immunological responses were monitored by determining autoantibodies in peripheral blood, and inflammatory reactions in the recipient site. Biopsies from the bone graft 6 months after grafting showed vital bone. After a mean observation period of 19.5 months, 22 of 23 implants were osseointegrated. None of the investigated autoantibodies were detected in peripheral blood, and there was no local inflammatory response. Allogeneic bone grafts in combination with titanium implants can be used in reconstruction of edentulous severely resorbed maxillae without immunological reactions directed against the graft.


Dry eye in Sjögren's syndrome - characteristics and therapy.
Sjögren's syndrome is an autoimmune disease, and its important feature is the lymphocyte infiltration of exocrine glands, including lacrimal glands. It contributes to defects of their activity and causes that one of the main manifestation of Sjögren's syndrome is dry eye. Unfortunately, the discrimination between dry eye related and non-related to Sjögren's syndrome is difficult at the initial stages of diseases. In addition, the available agents for the treatment of Sjögren's syndrome-related dry eye have limited efficacy. The purpose of this study was to describe and emphasize differences between Sjögren's Syndrome-related dry eye and non-Sjögren's Syndrome-related dry eye together with the determination of novel therapeutic options for Sjögren's Syndrome-related dry eye. A review of the relevant papers describing characteristics of Sjögren's Syndrome-related dry eye and its therapy was conducted. This article is based on both pre-clinical and clinical evidences. On the basis of our analysis, we indicated differences between Sjögren's Syndrome-related dry eye and non-Sjögren's Syndrome-related dry eye. Moreover, there are some novel markers that could be used in the diagnosis of Sjögren's Syndrome-related dry eye. In addition, expect artificial tear, other agents e.g. hydroxychloroquine can be effective in therapy of disease. Sjögren's Syndrome-related dry eye is a disorder, whose diagnosis may be difficult and mistaken for non-Sjögren's Syndrome-related dry eye. However, Sjögren's Syndrome-related dry eye has some specific features. In addition, the development of newer and safer therapeutic agents for Sjögren's syndrome-related dry eye is needed, and therefore further clinical, randomized studies are necessary.


Wilson's disease and diagnostic conundrum in a low income country.
Wilson's disease is a well-known leading cause of chronic liver disease in children. However it may remain undiagnosed in a resource limited setting for a long period. We describe a six year male child diagnosed Wilson's disease with extreme elevation of liver enzymes which is not reported earlier. The diagnosis was also baffling because of inconsistency of other laboratory parameters.


Occupational therapy students explore an area for future practice in HIV/AIDS community wellness.
Participating in community wellness projects is one way occupational therapy students at Winston-Salem State University (WSSU), Occupational Therapy Program in North Carolina are learning to expand occupational therapy into the community. In a fieldwork experience, 13 juniors are assigned to a community HIV/AIDS project to increase community awareness and prevention of the spread of HIV/AIDS. The project is implemented in conjunction with HOPE (HIV Outreach Programs and Education), STEP ONE, and the Samaritan Ministries. The students' efforts culminate in an HIV/AIDS Rally. Student learning is grouped into categories of planning, implementation, and follow up. This experience resulted in students working as volunteers for HOPE; students collaborating together on a research project to determine the extent University students understand how to prevent the spread of HIV; and students considering a WSSU campus-based HIV/AIDS awareness activity during October 2001 AIDS Awareness Month.


Identification of plant sterols in hexaploid and tetraploid wheats using gas chromatography with mass spectrometry.
Free sterols from hexaploid and tetraploid free-threshing wheats (Triticum aestivum L. and T. durum Desf.) and from their respective hulled wheats (T. spelta L. and T. dicoccon Schrank) were analysed by gas chromatography with mass spectrometry. The qualitative analysis of sterols showed a similar pattern either between hexaploid (T. aestivum, T. spelta) and tetraploid (T. durum, T. dicoccon) wheats or between free-threshing (T. aestivum, T. durum) and hulled (T. spelta, T. dicoccon) wheats. However, quantitative differences were found between tetraploid and hexaploid wheats, in that free sterol amounts in tetraploid wheats were 40% higher than in hexaploid ones. The mass spectra of the sterols were classified into four groups, taking into account the structural features of rings A and B. Typical mass spectral fragmentations of the four classes, and additional evidence related to the side chain of each molecule, were investigated together with their chromatographic behaviour, allowing identification of all the detected sterols.


Bite-angle bending as a key for understanding group-10 metal reactivity of d10-[M(NHC)2] complexes with sterically modest NHC ligands.
Synthesis, characterization and investigations on the reactivity of the novel metal basic, yet isolable 14 VE NHC-complexes [M0(iPr2Im)2] (M = Pd 3, Pt 4; iPr2Im = 1,3-di-isopropyl-imidazolin-2-ylidene; VE = valence electron; NHC = N-heterocyclic carbene) is reported and compared to the chemistry of the corresponding nickel complex. Quantum chemical analyses reveal that differences in the reactivity of group 10 NHC complexes are caused by differences in the rigidity and thus activation strain associated with bending the corresponding d10-[M(NHC)2] fragments during reaction. These results should have implications for the understanding of the fundamental steps in catalytic cycles, in which such complex fragments are employed.


Examining the impact of COVID-19 on health care utilization among persons with chronic spinal cord injury/dysfunction: a population study.
A retrospective longitudinal cohort time-series analysis study. To examine healthcare utilization and delivery during the COVID-19 pandemic in individuals with spinal cord injury/dysfunction (SCI/D). Health administrative database in Ontario, Canada. In 5754 individuals with SCI/D diagnosed from 2004-2014 and living in the community, healthcare utilization (physician visits, primary care visits, specialist visits, urologist visits, physiatrist visits, emergency department (ED) visits, and hospital admissions) and delivery (total, in-person, virtual) were determined at the (1) pre-pandemic period (March 2015 to February 2020), (2) initial pandemic onset period (March 2020-May 2020), and (3) pandemic period (June 2020 to March 2022). Autoregressive integrated moving average (ARIMA) modelling was conducted to determine the impact of the pandemic on monthly healthcare utilization and delivery. The initial pandemic onset period had a significant reduction of 24% in physicians (p = 0.0081), 35% in specialists (p < 0.0001), and 30% in urologist (p < 0.0001) visits, compared to pre-pandemic levels, with a partial recovery as the pandemic progressed. In April 2020, compared to the pre-pandemic period, a significant increase (p < 0.0001) in virtual visits for physicians, specialists, urologists, and primary care was found. The initial pandemic onset period had a 58% decrease in hospital admissions (p = 0.0011), compared to the pre-pandemic period. Healthcare utilization dropped in the initial pandemic onset period as physicians, specialists, and urologists, as well as hospitalization visits decreased significantly (p < 0.05) versus pre-pandemic levels. Virtual visit increases compensated for in-person visit decreases as the pandemic progressed to allow for total visits to partially recover.


Personal documents and nursing theory development.
Personal documents, notably autobiographical accounts, supply a compelling realm of phenomenological data for nursing theory, providing insight and understanding into the nonnormative nature of health and health-related experience. Personal documents occasion a discussion of empathic understanding as an analytical component of human science and illness as an occasion of heightened personal awareness. Triangulation research strategies are advocated as a means of incorporating personal experience data in nursing research.


Allelic variations of the Wx locus in cultivated rice and their use in the development of hybrid rice in China.
To make better use of global germplasm resources for improving the eating quality of hybrid rice, using the resequencing data from the 3,000 rice genomes project (3K RGP), the allelic variations of the rice Wx locus were analysed. With the exception of five rare alleles discovered for the first time in our study, most of these alleles were known alleles of Wx. Furthermore, a set of Kompetitive allele-specific PCR (KASP) markers based on these Wx alleles have been developed, and thirty-six main parents of hybrid rice from 1976 to 2018 were selected for Wx genotyping. The results showed that only three Wx alleles existed in the main parents of hybrids, and the allelic combination of the hybrids changed from Wxa/Wxb and Wxlv/Wxb to Wxb/Wxb with the development of hybrid rice. Wxb is widely used in the male parents of hybrid rice. Wxa and Wxlv were used in the female parents of early hybrid rice, and they were gradually replaced by Wxb. In the future, more favourable Wx alleles from cultivated rice should be identified, introduced, and effectively used to improve hybrid rice quality.


PI3K regulates pleckstrin-2 in T-cell cytoskeletal reorganization.
Pleckstrin-2 is composed of 2 pleckstrin homology (PH) domains and a disheveled-Egl-10-pleckstrin (DEP) domain. A lipid-binding assay revealed that pleckstrin-2 binds with greatest affinity to D3 and D5 phosphoinositides. Pleckstrin-2 expressed in Jurkat T cells bound to the cellular membrane and enhanced actin-dependent spreading only after stimulation of the T-cell antigen receptor or the integrin alpha4beta1. A pleckstrin-2 variant containing point mutations in both PH domains failed to associate with the Jurkat membrane and had no effect on spreading under the same conditions. Although still membrane bound, a pleckstrin-2 variant containing point mutations in the DEP domain demonstrated a decreased ability to induce membrane ruffles and spread. Pleckstrin-2 also colocalized with actin at the immune synapse and integrin clusters via its PH domains. Although pleckstrin-2 can bind to purified D3 and D5 phosphoinositides, the intracellular membrane association of pleckstrin-2 and cell spreading are dependent on D3 phosphoinositides, because these effects were disrupted by pharmacologic inhibition of phosphatidylinositol 3-kinase (PI3K). Our results indicate that pleckstrin-2 uses its modular domains to bind to membrane-associated phosphatidylinositols generated by PI3K, whereby it coordinates with the actin cytoskeleton in lymphocyte spreading and immune synapse formation.


Activating Photodynamic Therapy in vitro with Cerenkov Radiation Generated from Yttrium-90.
The translation of photodynamic therapy (PDT) to the clinical setting has primarily been limited to easily accessible and/or superficial diseases, for which traditional light delivery can be performed noninvasively. Cerenkov radiation, as generated from medically relevant radionuclides, has been suggested as a means to deliver light to deeper tissues noninvasively to overcome this depth limitation. This article investigates the utility of Cerenkov radiation, as generated from the radionuclide yttrium-90, for activating the PDT process using clinically approved aminolevulinic acid at 1.0 mm and also the more efficient porphyrin-based photosensitizer mesotetraphenylporphine with two sulfonate groups on adjacent phenyl rings (TPPS2a) at 1.2 µm. Experiments were conducted with monolayer cultured glioma and breast tumor cell lines. Although aminolevulinic acid proved to be ineffective for generating a therapeutic effect at all but the highest activity levels, TPPS2a produced at least a 20% therapeutic effect at activities ranging from 6 to 60 µCi/well for the C6 glioma cell line. Importantly, these results demonstrate for the first time, to our knowledge, that Cerenkov radiation generated from a radionuclide can be used to activate PDT using clinically relevant photosensitizers. These results therefore provide evidence that it may be possible to generate a phototherapeutic effect in vivo using Cerenkov radiation and clinically relevant photosensitizers.


Repeated episodes of myocardial ischaemia during combined thoracic epidural-isoflurane anaesthesia.
A patient with a history of coronary artery diseases developed new ST segment depressions in the ECG registration during a low dose (0.7%) isoflurane anaesthesia that was combined with a continuous thoracic epidural analgesia. Simultaneously a small decrease in mean arterial blood pressure (MAP) was noted. During the next 5 min these changes were followed by a severe drop in MAP (from 88 to 60 mmHg) and in cardiac output from 5.5 to 3.2 L/min. When isoflurane was discontinued both the ECG and the cardiovascular changes returned to the previous condition. Later, when 0.5% isoflurane was restarted, the ECG changes reappeared within ten min, but disappeared once again when isoflurane administration was discontinued. Thus, this patient had repeated episodes of myocardial ischaemia which were associated with the use of low dose isoflurane. Although isoflurane-induced "coronary steal" may appear as a likely cause of these ischaemic episodes, it is possible that the thoracic epidural had synergistic action and rendered the patient exceptionally sensitive to minor changes in perfusion pressure.


Dynamic analysis of splenic Th1 and Th2 lymphocyte functions in mice infected with Schistosoma japonicum.
Recent studies indicate that egg granuloma formation in murine Schistosoma mansoni infection is associated with Th2-mediated immune responses. The present study was designed to analyze dynamically the Th1 and Th2 responses in S. japonicum-infected animals and compare them with the results seen with S. mansoni. C3H mice were infected with 10 to 20 cercariae of S. japonicum and sacrificed 3 to 22 weeks later. Spleen cells were stimulated with parasite antigens (egg and adult worm) or the mitogen concanavalin A. Interleukin-2 (IL-2), IL-4, IL-5, and gamma interferon (IFN-gamma) levels were measured in the culture supernatants by enzyme-linked immunosorbent assay (ELISA) or bioassays. Additionally, cytokine-producing cells were enumerated by ELISPOT. The results show that Th2 cytokine production, characterized by IL-4 and IL-5, represents the major response in the first month after egg laying begins, while the Th1 functions of IFN-gamma and IL-2 production are greatly depressed. However, by 22 weeks Th2 responses have diminished and IFN-gamma production in response to concanavalin A is apparent. IL-2 responses are minimal at all times. In vitro depletion of T-cell subsets indicates that CD4+ cells are the major subset responsible for production of IL-5 at 7 weeks of infection. These findings suggest that, as in the case of S. mansoni infection, S. japonicum-induced immunopathology is temporally associated with the host Th2 response, although other experiments indicate that IFN-gamma is also involved.


Intraoral ligation of the maxillary artery for posterior epistaxis.
Intraoral ligation of the maxillary artery for intractable posterior epistaxis has been used effectively in 14 consecutive patients, all of whom had failed conventional anterior and posterior packing techniques. Fresh cadaver material was dissected in order to define the anatomic relationships of the infratemporal portion of the maxillary artery, as well as to develop the surgical technique prior to clinical application. The results indicate that this technique is rapid, safe, versatile, and effective in the majority of patients that require surgical interruption of the blood supply to the nose. The results of this study and the surgical technique are discussed.


Characterization of Antagonistic Bacillus methylotrophicus Isolated From Rhizosphere and Its Biocontrol Effects on Maize Stalk Rot.
Stalk rot is one of the most serious and widespread diseases in maize, and effective control measures are currently lacking. Therefore, this study aimed to develop a new biological agent to manage this disease. An antagonistic bacterial strain, TA-1, was isolated from rhizosphere soil and identified as Bacillus methylotrophicus based on morphological and biochemical characterization and 16S ribosomal RNA and gyrB gene sequence analyses. TA-1 exhibited a strong antifungal effect on the growth of Fusarium graminearum mycelium, with 86.3% inhibition at a concentration of 108 CFU per ml. Transmission electron microscopy showed that TA-1 could disrupt the cellular structure of the fungus, induce necrosis, and degrade the cell wall. Greenhouse and field trials were performed to evaluate the biocontrol efficacy of TA-1 on maize stalk rot, and the results of greenhouse experiment revealed that the bacterium significantly reduced disease incidence and disease index. Seeds treated with a 108 CFU ml-1 cell suspension had the highest disease suppression at 86.8%. Results of field trials show that seed bacterization with TA-1 could not only reduce maize stalk rot incidence but also increase maize height, stem diameter, and grain yield. The lipopeptide antibiotics were isolated from the culture supernatants of TA-1 and identified as surfactins and iturins. Consequently, B. methylotrophicus TA-1 is a potential biocontrol agent against maize stalk rot.


Molecular architecture of inner dynein arms in situ in Chlamydomonas reinhardtii flagella.
The inner dynein arm regulates axonemal bending motion in eukaryotes. We used cryo-electron tomography to reconstruct the three-dimensional structure of inner dynein arms from Chlamydomonas reinhardtii. All the eight different heavy chains were identified in one 96-nm periodic repeat, as expected from previous biochemical studies. Based on mutants, we identified the positions of the AAA rings and the N-terminal tails of all the eight heavy chains. The dynein f dimer is located close to the surface of the A-microtubule, whereas the other six heavy chain rings are roughly colinear at a larger distance to form three dyads. Each dyad consists of two heavy chains and has a corresponding radial spoke or a similar feature. In each of the six heavy chains (dynein a, b, c, d, e, and g), the N-terminal tail extends from the distal side of the ring. To interact with the B-microtubule through stalks, the inner-arm dyneins must have either different handedness or, more probably, the opposite orientation of the AAA rings compared with the outer-arm dyneins.


Emi2 enables centriole amplification during multiciliated cell differentiation.
Massive centriole amplification during multiciliated cell (MCC) differentiation is a notable example of organelle biogenesis. This process is thought to be enabled by a derived cell cycle state, but the key cell cycle components required for centriole amplification in MCC progenitors remain poorly defined. Here, we show that emi2 (fbxo43) expression is up-regulated and acts in MCC progenitors after cell cycle exit to transiently inhibit anaphase-promoting complex/cyclosome (APC/C)cdh1 activity. We find that this inhibition is required for the phosphorylation and activation of a key cell cycle kinase, plk1, which acts, in turn, to promote different steps required for centriole amplification and basal body formation, including centriole disengagement, apical migration, and maturation into basal bodies. This emi2-APC/C-plk1 axis is also required to down-regulate gene expression essential for centriole amplification after differentiation is complete. These results identify an emi2-APC/C-plk1 axis that promotes and then terminates centriole assembly and basal body formation during MCC differentiation.


Venous thrombosis and stenosis after peripherally inserted central catheter placement in children.
Peripherally inserted central catheters (PICCs) can lead to development of venous thrombosis and/or stenosis. The presence of venous thrombosis and/or stenosis may preclude children with chronic medical conditions from receiving lifesaving therapies, from hemodialysis in end-stage renal disease to total parenteral nutrition in short bowel syndrome. Several adult studies have found an association between PICCs and venous thrombosis and/or stenosis, but none has evaluated for this association in children. To determine the incidence of venous thrombosis and/or stenosis after PICC placement and identify factors that increase the risk of venous thrombosis and/or stenosis after PICC placement in children. We conducted a retrospective review of children ages 1-18 years with a PICC placed between January 2010 and July 2013 at our center, and included those who had at least one vascular imaging study of the ipsilateral extremity (Doppler ultrasound, venogram or MR angiogram) after PICC placement. Logistic regression was applied to determine risk factors for development of venous thrombosis and/or stenosis. One thousand, one hundred and ten upper extremity PICCs were placed, with 703 PICCs in the right and 407 PICCs in the left. Eight hundred fifty-one imaging studies (609 Doppler ultrasounds, 193 contrast venograms and 49 MR angiograms) were performed in 376 patients. The incidence of venous thrombosis and/or stenosis in the imaged cohort was 26.3%. PICC laterality, insertion site, duration, patient height to PICC diameter ratio, and number of PICCs per patient were not associated with development of venous thrombosis and/or stenosis. Additionally, primary diagnosis and symptoms at the time of imaging did not predict findings of venous thrombosis and/or stenosis. However, patients exposed to non-PICC central venous catheters (CVC) were more likely to develop venous thrombosis and/or stenosis (odds ratio 1.95, 1.10-3.45). More than a quarter of the vascular imaging studies performed in this study cohort showed previously unknown venous thrombosis and/or stenosis, irrespective of PICC laterality, insertion site, duration and size and the number of PICCs. A history of CVC was associated with a nearly two-fold increase in risk of venous thrombosis and/or stenosis after PICC placement. We suggest that PICCs and CVCs should be placed judiciously in all children, but especially in those with lifelong medical conditions who are more likely to incur direct consequences from limited vascular access.


Population-Based Evidence of Climate Change Adaptation in an Endangered Plant Endemic to a Biodiversity Hotspot.
Climate change is expected to impact both the population structure and geographic distribution of plants. Species distribution models are widely used to assess range shifts and the vulnerability of plants to climate change. Despite the abundance of modeling studies, little is known about how existing populations respond to climate change. We investigated the demographic structure and vulnerability to climate change in Anemone moorei, a sub-shrub with a highly restricted distribution in a biodiversity hotspot. We improved the distribution knowledge through intensive field work. We conducted a census of stem length as a proxy for age for all known populations. We used ensemble forecasting to project distributions considering 10 future climate scenarios and developed a novel climate change vulnerability index for the species' distribution. We found that the mean stem length decreases and the proportion of young plants increases, while the size of fruiting plants decreases as A. moorei faces greater climate change vulnerability. We interpret these results as evidence for the onset of recent adaptation to climate change, consisting of reduced adult longevity and an earlier onset of reproduction. As a result of these changes, the proportion of juveniles in the population increases.


Association of depression and smoking cessation: outcomes of an 18-year retrospective cohort study.
Depression is frequently associated with unsuccessful smoking cessation. In this study, we investigated the impact of depression history on smoking cessation success in a clinical setting. This retrospective study included 726 patients who visited our smoking cessation clinic between January 1, 2001, and December 31, 2018. Kaplan-Meier analyses and Cox proportional hazards regression models were used to perform univariate and multivariate analyses of smoking cessation success factors. Among the 726 patients, 76 had a history of depression and demonstrated significantly lower 12-week quit rate compared to those without (33.6% vs. 69.6%, p < .001). Multivariate Cox analysis revealed a significant association between abstinence rate and history of depression (hazard ratio 2.251, 95% CI 1.505-3.315, p < .001), history of schizophrenia (hazard ratio 2.716, 95% CI 1.427-4.840, p = .003), and Fagerström Nicotine Dependence Test scores (hazard ratio 1.519, 95% CI 1.053-2.197, p = .025). Our findings suggested that a history of depression is a significant prognostic factor for smoking cessation, underscoring the need for targeted interventions for patients with a history of depression. The findings of this study are subject to potential selection bias due to recruitment from a single hospital, which may limit the generalizability of our results. This study highlights the necessity for novel, specialized smoking cessation therapies to support patients with a history of depression in their cessation journey.


[Diagnosing value of fasting blood glucose on MODSE caused by pulmonary infection in elderly patients with diabetes].
To evaluate the clinical value of fasting blood glucose (FBG) in the diagnosis of multiple organ dysfunction syndrome (MODS) caused by pulmonary infection in elderly patients with diabetes. Patients over 65 years old with diabetic pulmonary infection admitted to Department of Cadres Ward of Bethune International Peace Hospital of PLA from July 2015 to December 2016 were enrolled. According to the patient's highest FBG level during pulmonary infection, all patients were divided in two groups. The cases whose FBG ≥ 8.83 mmol/L were served as suspicious multiple organ dysfunction syndrome in the elderly (MODSE) group, and those had FBG < 8.83 mmol/L were served as suspicious non-MODSE group. The incidence of MODSE in suspicious MODSE group and suspicious non-MODSE group was compared. The receiver operating characteristic curve (ROC) was drawn, and the clinical value of highest FBG in the diagnosis of MODSE caused by pulmonary infection in elderly patients with diabetes was assessed. 119 elderly patients with diabetes and pulmonary infection were enrolled in the analysis. All patients were male, with age of 76-105 years with an average of (89.41±4.16) years. Among 119 patients, 55 of them with suspected MODSE, 64 of them with suspected non-MODSE. The incidence of MODSE in suspicious MODSE group was significantly higher than that in suspicious non-MODSE group (78.2% vs. 12.5%), with statistically significant difference (χ 2 = 52.108, P = 0.000). The area under the ROC curve of the highest FBG for diagnosis of MODSE was 0.895, and 95% confidence interval (95%CI) was 0.839-0.951 (P < 0.001). When using FBG≥8.83 mmol/L to diagnose MODSE induced by pulmonary infection in elderly patients with diabetes, the sensitivity was 84.3% and the specificity was 82.4%. FBG≥8.83 mmol/L, as an indicator reflecting the changes of metabolic function, have a diagnostic value for MODSE caused by pulmonary infection in elderly patients with diabetes.


Management of the radial forearm free flap donor site with the vacuum-assisted closure (VAC) system.
The radial forearm free flap is a popular reconstructive flap in modern head and neck surgery. Poor wound healing at the forearm donor site is common and frequently results in tendon exposure. The Vacuum-Assisted Closure (VAC) system (Kinetic Concepts Inc., San Antonio, TX) is a topical negative pressure dressing that has been shown to improve skin graft viability when used as a bolster dressing. In this study, we investigated the use of the VAC system in the management of the radial forearm free flap donor site. A retrospective chart review was performed on all subjects who underwent a radial forearm free flap reconstruction in which the VAC system was used as a bolster dressing at the donor site from January 1, 2003, through March 31, 2005. Thirty-four consecutive subjects were included in the study. Exposed tendon did not occur in 14 (0%) subjects in which the VAC bolster was used for a minimum of 6 days. Eleven of the 20 subjects (55%) who used the VAC bolster for 5 days demonstrated small amounts of tendon exposure (<2 cm) on follow-up clinic examination. The minimum follow up for all subjects was 4 months. This study demonstrates that the VAC system is a feasible alternative to conventional bolster dressing in the management of the radial forearm free flap skin-grafted donor site. Based on this study, when used for a minimum of 6 days, the VAC bolster dressing eliminated tendon exposure at the forearm donor site.


Large-scale, multibreed, multitrait analyses of quantitative trait loci experiments: the case of porcine X chromosome.
A QTL analysis of multibreed experiments (i.e., crossed populations involving more than two founder breeds) offers clear advantages over classical two-breed crosses, among them increased power and a more comprehensive coverage of the total genetic variability in the species. An alternative to designed multibreed crosses is to reanalyze jointly several experiments involving different breeds. We report a multibreed, multitrait QTL analysis of SSCX that involves five different crosses, six breeds, and almost 3,000 genotyped individuals using a truly multibreed strategy to allow for any number of founder breed origins. Traits analyzed were growth, fat thickness, carcass length, and shoulder and ham weights. Generally, the joint analysis resulted in more significant QTL than the single-experiment analyses. We show that the QTL for fatness, which is highly significant (nominal P < 10(-43)), is of Asiatic origin (Meishan). The next most significant QTL (nominal P < 10(-15)) affected ham weight and seems to be segregating only between Large White and the rest of the breeds. A multitrait, multi-QTL analysis suggests that these are two distinct loci. Additionally, a locus segregating only between Iberian and Landrace affects live weight. The advantages of joint, multibreed analyses clearly outweigh their potential risks.


Off-pump coronary artery bypass surgery in dextrocardia: a report of two cases.
Dextrocardia is a rare condition that may be congenital (situs inversus) or acquired (pseudodextrocardia). Since individuals with this ailment have normal cardiac physiology and function, they may live normal lives. Similar to the general population, however, they might be susceptible to ischemic heart disease and present to a cardiothoracic surgical department for coronary artery bypass surgery. We report two cases: one of dextrocardia (situs inversus) and another resulting from an elevation of the left hemidiaphragm, causing pseudodextrocardia. To operate on patients with dextrocardia, surgeons may need to make a few modifications. These include using the right internal mammary artery as a conduit for the "left" anterior descending artery, lengthening the left internal mammary artery to reach the left anterior descending artery, and sometimes the operating surgeon may need to stand at the left side of the operating table. The careful planning of work on the conduits in the preoperative period requires prudence. This report highlights the surgical difficulties during operations on patients with situs inversus or pseudodextrocardia.


Perceived variability and symbol use: a common language-cognition interface in children and chimpanzees (Pan troglodytes).
Analysis of two chimpanzees' conversations with their teacher during a tool-use training task demonstrated that chimps use lexigrams, a humanly devised visual symbol system, selectively to encode perceived variability; that is, they generally used their symbols to differentiate alternative possibilities or to represent change or novelty in a situation. In contrast, they tended to leave unsaid what was unchanging, repetitive, or the unique possibility in a situation. Perceived variability influenced not only which symbols were selected but also utterance length: A single dimension of variability in a situation leads to single-lexigram utterances; multiple dimensions are associated with multi-lexigram utterances. This pattern of results indicates that the absence of formal grammatical structure in chimp language does not imply that utterances beyond one word in length are either rote strings or imitations. The chimps' tendency to mention the variable while leaving the constant or redundant unsaid is, moreover, strong support for the position that their use of a humanly devised symbol system is more than a series of conditioned responses.


Medical practice and manuscripts in Byzantium.
Scholars, past and present, have belittled Byzantine medicine for its perceived static and derivative nature. Applied to the medicine of the centuries immediately before and after the year 1000, these criticisms, though apparently sustainable, fail to recognize its underlying vigour. It was a practical craft medicine, and one which used elements of magic and religion to compensate for the intractability of the many diseases that were not amenable to medicine. These centuries were a time when hospitals flourished in Byzantium, and this paper assembles and describes some of the manuscripts that can be associated with them. The influence of islamic medicine, which had hitherto borrowed from Byzantium, is also examined. If the Byzantine medicine of this period could not claim great originality or innovation, it had none the less distilled what was best and most useful from the long and often complex medical writings of antiquity, ensured its transmission, and preserved much from earlier times that would otherwise now be lost.


Traumatic stress in Egyptian doctors during COVID-19 pandemic.
COVID-19 pandemic has heavily burdened healthcare systems throughout the world, causing substantial mental distress to medical professionals. We aim to investigate the associated traumatic stress in a sample of practicing physicians in Egypt during the COVID-19 pandemic. This cross-sectional study assessed depression, and Post-traumatic stress disorder (PTSD) among a sample of Egyptian physicians using an electronic survey. It included demographic and practice-related data, PTSD Checklist - Civilian Version (PCL-C) and the nine-item Patient Health Questionnaire (PHQ-9). Of the 124 respondents, 66.9% were at high risk for depression and 37.9% met criteria for diagnosis of PTSD. Female gender and perceived work-related stress were significantly associated with PTSD. PTSD and depression severity scores were positively correlated. These findings highlight the importance of timely mental support and intervention for medical workers.


Chylomicrons Regulate Lacteal Permeability and Intestinal Lipid Absorption.
Lymphatic vessels are responsible for tissue drainage, and their malfunction is associated with chronic diseases. Lymph uptake occurs via specialized open cell-cell junctions between capillary lymphatic endothelial cells (LECs), whereas closed junctions in collecting LECs prevent lymph leakage. LEC junctions are known to dynamically remodel in development and disease, but how lymphatic permeability is regulated remains poorly understood. We used various genetically engineered mouse models in combination with cellular, biochemical, and molecular biology approaches to elucidate the signaling pathways regulating junction morphology and function in lymphatic capillaries. By studying the permeability of intestinal lacteal capillaries to lipoprotein particles known as chylomicrons, we show that ROCK (Rho-associated kinase)-dependent cytoskeletal contractility is a fundamental mechanism of LEC permeability regulation. We show that chylomicron-derived lipids trigger neonatal lacteal junction opening via ROCK-dependent contraction of junction-anchored stress fibers. LEC-specific ROCK deletion abolished junction opening and plasma lipid uptake. Chylomicrons additionally inhibited VEGF (vascular endothelial growth factor)-A signaling. We show that VEGF-A antagonizes LEC junction opening via VEGFR (VEGF receptor) 2 and VEGFR3-dependent PI3K (phosphatidylinositol 3-kinase)/AKT (protein kinase B) activation of the small GTPase RAC1 (Rac family small GTPase 1), thereby restricting RhoA (Ras homolog family member A)/ROCK-mediated cytoskeleton contraction. Our results reveal that antagonistic inputs into ROCK-dependent cytoskeleton contractions regulate the interconversion of lymphatic junctions in the intestine and in other tissues, providing a tunable mechanism to control the lymphatic barrier.


Development of a microassay for estradiol receptors.
The calculation of equilibrium binding constants for a specific receptor-hormone interaction requires the exact determination of the unbound ligand concentration and the specifically bound concentration at equilibrium. These determinations usually require corrections for the contribution of non-specific binding. We introduce several parameters allowing equilibrium concentrations to be calculated from experimental concentration values; these parameters can be measured for the particular receptor assay procedure used. These parameters are used in a microassay of estradiol-receptor complex by selective retention on DE-81 cellulose paper.


ASIC3 fine-tunes bladder sensory signaling.
Acid-sensing ion channels (ASICs) are trimeric proton-activated, cation-selective neuronal channels that are considered to play important roles in mechanosensation and nociception. Here we investigated the role of ASIC3, a subunit primarily expressed in sensory neurons, in bladder sensory signaling and function. We found that extracellular acidification evokes a transient increase in current, consistent with the kinetics of activation and desensitization of ASICs, in ~25% of the bladder sensory neurons harvested from both wild-type (WT) and ASIC3 knockout (KO) mice. The absence of ASIC3 increased the magnitude of the peak evoked by extracellular acidification and reduced the rate of decay of the ASIC-like currents. These findings suggest that ASICs are assembled as heteromers and that the absence of ASIC3 alters the composition of these channels in bladder sensory neurons. Consistent with the notion that ASIC3 serves as a proton sensor, 59% of the bladder sensory neurons harvested from WT, but none from ASIC3 KO mice, fired action potentials in response to extracellular acidification. Studies of bladder function revealed that ASIC3 deletion reduces voiding volume and the pressure required to trigger micturition. In summary, our findings indicate that ASIC3 plays a role in the control of bladder function by modulating the response of afferents to filling.


Crystallographic plane tuning of magnetoplasmon excitations in two-dimensional electron gas systems.
We investigate theoretically the magnetoplasmon spectrum of two-dimensional electron gas systems grown along different crystallographic directions, which are modulated by both the Dresselhaus spin-orbit interaction (DSOI) and the Rashba spin-orbit interaction (RSOI). Because the DSOI depends on the crystallographic orientation, the magnetoplasmon spectrum in the presence of the DSOI shows distinct features for different crystallographic planes. For some high-index planes, such as (140) and (114), the magnetoplasmon spectrum is anisotropic even under the pure-DSOI modulation, which is different from the isotropic behavior for the high-symmetry (001) plane. The coexistence of the DSOI and the RSOI leads to more drastic variations of the anisotropic magnetoplasmon spectrum in different crystallographic planes, which are revealed from the splittings of the collective excitation modes and the intensity of the spin density excitation at the anticrossing center of the splittings.


Sequence-independent assembly of spermatid mRNAs into messenger ribonucleoprotein particles.
During mammalian spermatogenesis, meiosis is followed by a brief period of high transcriptional activity. At this time a large amount of mRNA is stored as messenger ribonucleoprotein (mRNP) particles. All subsequent processes of sperm maturation occur in the complete absence of transcription, primarily using proteins which are newly synthesized from these stored mRNAs. By expressing transgene mRNAs in the early haploid spermatids of mice, we have investigated the sequence requirements for determining whether specific mRNAs in these cells will be stored as mRNP particles or be assembled into polysomes. The results suggest that mRNAs which are transcribed in spermatids are assembled into mRNP particles by a mechanism that acts independently of mRNA sequence. Our findings reveal a fundamental similarity between the mechanisms of translational control used in spermatogenesis and oogenesis.


Feasibility of Left Atrial Appendage Occlusion Without Preprocedural Transesophageal Echocardiography or CT Scanning.
To assess the success rate and safety outcomes of left atrial appendage occlusion (LAAO) procedures in a cohort of patients who had not undergone preprocedural imaging. LAAO patients usually undergo imaging with either transesophageal echocardiography (TEE) or computed tomography (CT) prior to the procedure itself. This preprocedural imaging may not be necessary. The procedural success and major complication rates were assessed in a cohort of 52 patients who underwent LAAO without preprocedural imaging. Mean patient age was 75 ± 8 years. Median CHA2DS2-VASc score was 4 and median HASBLED score was 3. The LAAO procedure was successful in 51/52 cases (98.1%). In 1 case, the LAAO procedure did not proceed because the LAA was too large for the available occlusion devices. No patient had left atrial appendage thrombus, despite the fact that only 4 patients were taking oral anticoagulation therapy at the time. Major complications occurred in 2/52 cases (3.8%), both due to vascular injuries causing pseudoaneurysm formation. LAAO in this series was not adversely affected by lack of preprocedural imaging. Omitting preprocedural imaging reduces risk attributable to the modality, reduces patient inconvenience and discomfort, reduces cost, and does not appear to significantly reduce the proportion of patients who can undergo a successful procedure. Further larger studies are warranted.


Accessing orthographic representations from speech: the role of left ventral occipitotemporal cortex in spelling.
The present fMRI study used a spelling task to investigate the hypothesis that the left ventral occipitotemporal cortex (vOT) hosts neuronal representations of whole written words. Such an orthographic word lexicon is posited by cognitive dual-route theories of reading and spelling. In the scanner, participants performed a spelling task in which they had to indicate if a visually presented letter is present in the written form of an auditorily presented word. The main experimental manipulation distinguished between an orthographic word spelling condition in which correct spelling decisions had to be based on orthographic whole-word representations, a word spelling condition in which reliance on orthographic whole-word representations was optional and a phonological pseudoword spelling condition in which no reliance on such representations was possible. To evaluate spelling-specific activations the spelling conditions were contrasted with control conditions that also presented auditory words and pseudowords, but participants had to indicate if a visually presented letter corresponded to the gender of the speaker. We identified a left vOT cluster activated for the critical orthographic word spelling condition relative to both the control condition and the phonological pseudoword spelling condition. Our results suggest that activation of left vOT during spelling can be attributed to the retrieval of orthographic whole-word representations and, thus, support the position that the left vOT potentially represents the neuronal equivalent of the cognitive orthographic word lexicon.


A liquid-Ga-filled carbon nanotube: a miniaturized temperature sensor and electrical switch.
Temperature control on the nanometer scale is a challenging task in many physical, chemical, and material science applications where small experimental volumes with high temperature gradients are used. The crucial difficulty is reducing the size of temperature sensors while keeping their sensitivity, working temperature range, and, most importantly, their simplicity and accuracy of temperature reading. In this work, we demonstrate the ultimate miniaturization of the classic thermometer using an expanding column of liquid gallium inside a multi-walled C nanotube for precise temperature measurements. We report that electrical conductivity through unfilled nanotube regions is diffusive with a resistance per unit length of approximately 10 kOmega microm(-1), whereas Ga-filled segments of the nanotube show metallic behavior with a low resistance of approximately 100 Omega microm(-1). No noticeable Schottky barrier exists between the nanotube carbon shell and the inner Ga filling. Based on these findings, an individual carbon nanotube partially filled with liquid Ga is used as a temperature sensor and/or switch. The nanotube's electrical resistance decreases linearly with increasing temperature as the metallic Ga column expands inside the tube channel. In addition, the tube resistance drops sharply when two encapsulated Ga columns approaching each other meet inside the nanotube, producing a switching action that can occur at any predetermined temperature, as the Ga column position inside the nanotube can be effectively pre-adjusted by nanoindentation using an atomic force microscope.


Biochemical characterization of secreted proteases during growth in Tetrahymena pyriformis WH-14: comparison of extracellular with intracellular proteases.
Tetrahymena pyriformis strain WH-14 secreted large quantities of intracellular proteases into its culture medium during growth. Extracellular enzymes were purified to homogeneity from cell-free medium by ammonium sulfate precipitation, CM-Sephadex column chromatography, gel filtration, and DEAE-cellulose column chromatography. The DEAE-cellulose eluates were separated into four peaks (P-I, P-II, P-III, and P-IV), each of which exhibited a different specific activity toward azocasein and alpha-N-benzoyl-DL-arginine-rho-nitroanilide (Bz-Arg-Nan). These four forms of the protease showed similarity in amino acid composition, molecular weight (21,000-24,000), and antigenic reactivity. They had pH optima at neutral range. P-I showed the highest specificity to azocasein whereas P-IV was most effective toward the synthetic substrates. The Km values for hydrolysis of Bz-Arg-Nan were 2.4, 1.6, 1.3 and 1.4 mM for P-I, P-II, P-III, and P-IV, respectively, and the corresponding Kcat/Km values were 5.0, 9.4, 28.5, and 114.3 S-1 . M-1. These properties of secreted proteases were compared with those of intracellular proteases purified by the same procedure except for the initial Triton X-100 extraction. There were similarities in specific activity toward two substrates, molecular weight, Km, pH optima, and antigenic reactivity between the proteases from two sources, providing evidence that the intracellular proteases may be secreted into the extracellular medium without modification.


Beta-adrenergic stimulation of calcium channels occurs by potentiation of high-activity gating modes.
cAMP-dependent phosphorylation clearly increases current through cardiac L-type Ca channels, but the molecular manifestation of this effect remains controversial. Previous work implicates either an increase in the number of functional channels or graded changes in the gating of individual channels. We now find that single cardiac Ca channels display three patterns of activity ("modes") and that isoproterenol or 8-bromoadenosine 3',5'-cyclic monophosphate redistributes the relative proportions of modes such that the two most active (mode 1, bursts of brief openings; mode 2, very long-lasting openings) are favored (P less than 0.05; n = 7). Conversely, a pattern of sparse brief openings (mode 0a) is selectively inhibited (P less than 0.01). Despite differences in the relative frequencies of the various modes before and during drug exposure, the gating within each mode is not detectably changed. We conclude that potentiation of highly active modes of Ca channel gating underlies the enhancement of calcium influx by beta-adrenergic stimulation.


Regulation of chloride transport in parotid secretory granules by membrane fluidity.
Zymogen granule membranes contain Cl- conductance and Cl/anion exchange activities that become important for primary fluid production after fusion with the apical plasma membrane of the acinar cell. We have used steady-state fluorescence anisotropy of diphenylhexatriene derivatives and measurements of Cl- transport in isolated secretory granules to determine the contribution of membrane fluidity to the regulation of transport across the granule membrane. Secretory granules from several unstimulated glands (rat pancreas and parotid, rabbit gastric glands) were shown to have low membrane fluidity compared to plasma membranes. In addition, Cl- transport activity in different granule preparations showed a strong correlation to the membrane fluidity when measured with 1-[4-(trimethylammonio)phenyl]-6-phenyl-1,3,5-hexatriene p-toluenesulfonate (TMA-DPH), but not with 3-[p-(6-phenyl)-1,3,5-hexatrienyl)-phenyl]propionic acid (PA-DPH). These data suggest that TMA-DPH preferentially partitions into a specific lipid environment associated with, or which exerts an influence on, the Cl- transport proteins and that increases in the fluidity of this environment are associated with higher transport rates. Data from other types of plasma membranes indicate that TMA-DPH partitions much more than PA-DPH into the cytoplasmic leaflet, suggesting that this part of the granule membrane is involved in the observed fluidity changes. Furthermore, increasing the bulk membrane fluidity with the local anesthetics benzyl alcohol and n-alkanols increased the Cl- transport rates up to 10-fold. This increase was apparently through specific transporters as anion selectivity was maintained in spite of the higher absolute rates.(ABSTRACT TRUNCATED AT 250 WORDS)


Prediction of Motor Recovery in Patients with Basal Ganglia Hemorrhage Using Diffusion Tensor Imaging.
Predicting prognosis in patients with basal ganglia hemorrhage is difficult. This study aimed to investigate the usefulness of diffusion tensor imaging in predicting motor outcome after basal ganglia hemorrhage. A total of 12 patients with putaminal hemorrhage were included in the study (aged 50 ± 12 years), 8 patients were male (aged 46 ± 11 years) and 4 were female (aged 59 ± 9 years). We performed diffusion tensor imaging and measured clinical outcome at baseline (pre) and 3 weeks (post1), 3 months (post2), and 6 months (post3) after the initial treatment. In the affected side of the brain, the mean fractional anisotropy (FA) value on pons was significantly higher in the good outcome group than that in the poor outcome group at pre (p = 0.004) and post3 (p = 0.025). Pearson correlation analysis showed that mean FA value at pre significantly correlated with the sum of the Brunnstrom motor recovery stage scores at post3 (R = 0.8, p = 0.002). Change in the FA ratio on diffusion tractography can predict motor recovery after hemorrhagic stroke.


The ins and outs of periodontal antimicrobial therapy.
A multifaceted antimicrobial approach is necessary for the successful management of destructive periodontal disease. Effective antimicrobial periodontal therapy aims to overwhelm periodontal pathogens with aggressive initial therapy and prevent previously suppressed pathogens from rising up anew through daily oral hygiene measures and frequent professional cleaning. Current antimicrobial periodontal therapy employs mechanical debridement performed with and without surgery, antibiotics, and antiseptics. Subgingival irrigation with povidone-iodine at the dentist's office and subgingival irrigation with dilute sodium hypochlorite for home-care constitute effective, safe, and affordable periodontal antimicrobial therapy. This article describes theoretical and practical guidelines for implementing rational and cost-effective antimicrobial principles in the management of periodontal disease.


Vertical signalling involves transmission of Hox information from gastrula mesoderm to neurectoderm.
Development and patterning of neural tissue in the vertebrate embryo involves a set of molecules and processes whose relationships are not fully understood. Classical embryology revealed a remarkable phenomenon known as vertical signalling, a gastrulation stage mechanism that copies anterior-posterior positional information from mesoderm to prospective neural tissue. Vertical signalling mediates unambiguous copying of complex information from one tissue layer to another. In this study, we report an investigation of this process in recombinates of mesoderm and ectoderm from gastrulae of Xenopus laevis. Our results show that copying of positional information involves non cell autonomous autoregulation of particular Hox genes whose expression is copied from mesoderm to neurectoderm in the gastrula. Furthermore, this information sharing mechanism involves unconventional translocation of the homeoproteins themselves. This conserved primitive mechanism has been known for three decades but has only recently been put into any developmental context. It provides a simple, robust way to pattern the neurectoderm using the Hox pattern already present in the mesoderm during gastrulation. We suggest that this mechanism was selected during evolution to enable unambiguous copying of rather complex information from cell to cell and that it is a key part of the original ancestral mechanism mediating axial patterning by the highly conserved Hox genes.


Guide Picker is a comprehensive design tool for visualizing and selecting guides for CRISPR experiments.
Guide Picker ( https://www.deskgen.com/guide-picker/ ) serves as a meta tool for designing CRISPR experiments by presenting ten different guide RNA scoring functions in one simple graphical interface. It allows investigators to simultaneously visualize and sort through every guide targeting the protein-coding regions of any mouse or human gene. Utilizing a multidimensional graphical display featuring two plots and four axes, Guide Picker can analyze all guides while filtering based on four different criteria at a time. Guide Picker further facilitates the CRISPR design process by using pre-computed scores for all guides, thereby offering rapid guide RNA generation and selection. The ease-of-use of Guide Picker complements CRISPR itself, matching a powerful and modular biological system with a flexible online web tool that can be used in a variety of genome editing experimental contexts.


Understanding Symmetric Smoothing Filters: A Gaussian Mixture Model Perspective.
Many patch-based image denoising algorithms can be formulated as applying a smoothing filter to the noisy image. Expressed as matrices, the smoothing filters must be row normalized, so that each row sums to unity. Surprisingly, if we apply a column normalization before the row normalization, the performance of the smoothing filter can often be significantly improved. Prior works showed that such performance gain is related to the Sinkhorn-Knopp balancing algorithm, an iterative procedure that symmetrizes a row-stochastic matrix to a doubly stochastic matrix. However, a complete understanding of the performance gain phenomenon is still lacking. In this paper, we study the performance gain phenomenon from a statistical learning perspective. We show that Sinkhorn-Knopp is equivalent to an expectation-maximization (EM) algorithm of learning a Gaussian mixture model of the image patches. By establishing the correspondence between the steps of Sinkhorn-Knopp and the EM algorithm, we provide a geometrical interpretation of the symmetrization process. This observation allows us to develop a new denoising algorithm called Gaussian mixture model symmetric smoothing filter (GSF). GSF is an extension of the Sinkhorn-Knopp and is a generalization of the original smoothing filters. Despite its simple formulation, GSF outperforms many existing smoothing filters and has a similar performance compared with several state-of-the-art denoising algorithms.


Modeling the airway epithelium in allergic asthma: interleukin-13- induced effects in differentiated murine tracheal epithelial cells.
Mucous cells of the airway epithelium play a crucial role in the pathogenesis of human inflammatory airway diseases. Therefore, it is of importance to complement in vivo studies that use murine models of allergic asthma with in vitro mechanistic studies that use murine airway epithelial cells, including mucus-containing cells. In this study, we report the development and characterization of an in vitro culture system for primary murine tracheal epithelial (MTE) cells comprising ciliated cells and a substantial number of mucous cells. The increase in mucous cell number over that observed in the native murine airway, or in previously described murine cultures, creates a culture intermediate between the in vivo murine airway epithelium and in vitro cultures of human airway epithelial cells. To establish the usefulness of this culture system for the study of epithelial effects during inflammatory airway diseases, the cells were exposed to interleukin (IL)-13, a central inflammatory mediator in allergic asthma. The IL-13 induced two characteristic epithelial effects, proliferation and modulation of MUC5AC gene expression. There was a concentration dependence of these events, wherein high concentrations of IL-13 (10 ng/ml) induced proliferation, whereas lower concentrations (1 ng/ml) increased MUC5AC mRNA (where mRNA is messenger RNA). Interestingly, these effects occurred in an inverse manner, with the high concentration of IL-13 also provoking a significant decrease in MUC5AC gene expression. Thus, MTE cells cultured in this manner may provide an important link between experimental findings from animal models of allergic asthma and their application to human disease.


Marine n-3 polyunsaturated fatty acids affect the blood pressure control in patients with newly diagnosed hypertension - a 1-year follow-up study.
Marine long-chained n-3 polyunsaturated fatty acids (PUFA) are recognized for their cardio-protective effects, including potential lowering of blood pressure. We hypothesized that higher habitual fish intake and n-3 PUFA plasma levels were associated with lower blood pressure and being less likely to receive antihypertensive medication after one-year follow-up. In this prospective study of 115 patients, we assessed 24 h ambulatory and central blood pressure, plasma phospholipid fatty acid composition using gas chromatography and participants completed a food frequency questionnaire, including fish-eating habits. All measurements were repeated at one-year follow-up. At baseline, patients consuming fish ≥2 times per month for dinner had significantly higher plasma levels of total marine n-3 PUFA, docosahexaenoic acid and eicosapentaenoic acid as well as significantly lower central blood pressure and a trend towards lower peripheral blood pressure. At follow-up, 21 patients (18%) without antihypertensive medication had significantly higher plasma levels of n-3 PUFA, docosahexaenoic acid and eicosapentaenoic acid as well as a higher, but still acceptable 24 h ambulatory blood pressure (137/85 mmHg) compared to subjects receiving antihypertensive medication. The untreated group was more prone to take fish oil capsules and increased their plasma levels of n-3 PUFA compared to baseline. In patients with newly diagnosed, untreated hypertension, regular fish consumption was accompanied by lower blood pressure. After one year, patients without antihypertensive medication were characterized by a significant increase and higher plasma levels of n-3 PUFA. This supports a blood pressure-lowering effect and suggests an increase in marine n-3 PUFA intake as part of non-pharmacological treatment of hypertension.


Nutritional support in acute pancreatitis.
Acute pancreatitis is one of the most catabolic of critical illnesses, and its clinical course is often prolonged. Consequently, the need for interventional nutritional support is great. Because of fears that feeding might exacerbate the tryptic autodigestion and disease process, total parenteral nutrition was used exclusively until recent years, when it was recognized that the complications of hyperglycemia and sepsis outweighed nutritional benefits. In clinical practice, enteral feeding has proven superior because it avoids these complications and maintains gut function, but enteral feeding needs to be given in a form that minimizes pancreatic stimulation. This review discusses the advances in our understanding of the pathophysiology of the disease, the results of recent clinical trials of nutritional support, and the challenges that remain in optimizing nutritional management.


The covalently bound diazo group as an infrared probe for hydrogen bonding environments.
Covalently bound diazo groups are frequently found in biomolecular substrates. The C[double bond, length as m-dash]N[double bond, length as m-dash]N asymmetric stretching vibration (νas) of the diazo group has a large extinction coefficient and appears in an uncongested spectral region. To evaluate the solvatochromism of the C[double bond, length as m-dash]N[double bond, length as m-dash]N νas band for studying biomolecules, we recorded the infrared (IR) spectra of a diazo model compound, 2-diazo-3-oxo-butyric acid ethyl ester, in different solvents. The width of the C[double bond, length as m-dash]N[double bond, length as m-dash]N νas band was linearly dependent on the Kamlet-Taft solvent parameter, which reflects the polarizability and hydrogen bond accepting ability of the solvent. Therefore, the width of the C[double bond, length as m-dash]N[double bond, length as m-dash]N νas band could be used to probe these properties for a solvent. We found that the position of the C[double bond, length as m-dash]N[double bond, length as m-dash]N νas band was linearly correlated with the density of hydrogen bond donor groups in the solvent. We studied the relaxation dynamics and spectral diffusion of the C[double bond, length as m-dash]N[double bond, length as m-dash]N νas band of a natural amino acid, 6-diazo-5-oxo-l-norleucine, in water using nonlinear IR spectroscopy. The relaxation and spectral diffusion time constants of the C[double bond, length as m-dash]N[double bond, length as m-dash]N νas band were similar to those of the N[double bond, length as m-dash]N[double bond, length as m-dash]N νas band. We concluded that the position and width of the C[double bond, length as m-dash]N[double bond, length as m-dash]N νas band of the diazo group could be used to probe the hydrogen bond donating and accepting ability of a solvent, respectively. These results suggest that the diazo group could be used as a site-specific IR probe for the local hydration environments.


What is an "organism"? On the occurrence of a new term and its conceptual transformations 1680-1850.
The essay reconstructs the occurrence of the term "organism" and the transformations of its concept from around 1680 to the middle of the nineteenth century. The different sections refer to individual authors who used the word "organism" and situate its usage in specific historical contexts. After earlier uses of the word in medieval sources, the Latin word "organismus" appeared in 1684 in Stahl's medico-physiological writings. Around 1700, it can be found in French (organisme), English (organism), Italian (organismo) and later also in German (Organismus). During the eighteenth century, the word "organism" generally referred to a specific principle or form of order, often in opposition to the order of "mechanism," that could be applied to plants, animals or the entire world. At the end of the eighteenth century, the term became a generic name for individual living entities with inside-outside-interfaces and an inner "organization" of parts. From around 1830, the word "organism" replaced the expressions "organic" or "organized body" as a recurrent technical term in the emerging biological disciplines.


[The evolution of nursing shortage and strategies to face it: a longitudinal study in 11 hospitals].
To describe the perception of the evolution of nursing shortage from 2000 to 2009 according to Nursing Coordinators and the strategies to face it. Nursing coordinators of 11 hospitals or districts of Friuli Venezia Giulia, Trentino Alto Adige and Veneto regions were interviewed in 2000, 2004 and 2009 to collect data and assess their perception on nurses' shortage. In the first interview the medium gap between staff planned and in service was -5.4%; in 2004 -9.4% and in 2009 -3.3%. The shortage, once with a seasonal trend is now constant and appreciated in all the wards. In years 2000 and 2004 on average 5 strategies to face the shortage were implemented, in 2009 7. No systematic strategies have been used with the exception of the unification of wards, mainly during summer for letting people go on holydays. According to Nursing Coordinators the effects of the shortage are already observable (although not quantified) on patients and nurses. The nurses' shortage has been one of the challenges of the last 10 years. Its causes have changed but not the strategies implemented.


Two novel alkaloids with a unique fused hexacyclic skeleton from Daphniphyllum subverticillatum.
Two novel major alkaloids, deoxycalyciphylline B (1) and deoxyisocalyciphylline B (2) with a unique fused hexacyclic skeleton, together with a quite recently reported alkaloid calyciphylline B (3), were isolated from the stem of Daphniphyllum subverticillatum. Their structures were established by spectral methods and chemical evidence, especially 2D NMR techniques. The structure of 1 was further confirmed by a single-crystal X-ray diffraction determination.


Differential interference by azathioprine and 6-mercaptopurine with antibody-mediated immunoregulation: synergism of azathioprine and antibody in the control of an immune response.
Comparative studies on the effects of immunosuppressive agents azathioprine (AZ) and 6-mercaptopurine (6-MP) in antibody-mediated immunoregulation are reported. To determine the degree of interference of these agents with the generation of antibody molecules controlling an anti-SRBC response, the donors of mouse anti-SRBC sera were given daily doses of the drugs. Primary antisera from AZ-treated donors were not significantly inhibited by daily doses of 180, 270, and 360 mumol/kg in their ability to suppress the direct PFC response; on the other hand 6-MP was inhibitory at the two higher equimolar dose levels. When the antisera were used in the antibody-dependent cellular cytotoxicity (ADCC) and phagocytosis (AD phi) assays, similar differential effects of the two agents were found. Multiple doses of AZ and 6-MP given to the donors of ADCC effector cells enhanced the capacity of these cells to lyse antibody-sensitized SRBC target cells. The enhancement of ADCC with 6-MP was less manifest than that with AZ. When injected before the antigen, AZ acted synergistically with the antibody in the control of the direct PFC response. Possible mechanisms by which AZ can interact with antibody-mediated immune regulation are discussed.


A low-cost FES exercise bicycle for training paraplegics at home.
The success of FES exercise programmes for training paraplegic muscles at home depends highly upon the availability of reliable, easy-to-use and inexpensive training equipment. For endurance training, FES bicycle exercisers are well accepted. However, they are not suited for home use due to the high expense of commercially available equipment. This paper describes the development of a FES exercise bicycle for use at home. It consists of a standard bicycle ergometer with minimum modifications. The exerciser can be used by the patient sitting in the wheelchair, and may be used with any two-channel muscle stimulator.


[Therapy outcome in stage III (FIGO) ovarian carcinomas at the Leipzig University Gynecologic Clinic 1976-1982 and 1985-1991].
This retrospective study compares treatment results (median survival time, 5-year survival rate) of 153 patients diagnosed with FIGO stage III ovarian cancer treated between 1976 to 1982 (n = 73) and 1985 to 1991 (n = 80) respectively. Between 1976 to 1982, the median survival time was 12.3 months, while it increased up to 17.0 months during the period of 1985-1991. The 5-year survival rate increased from 14.0% to 28.0%. This improvement may be due to a more radical surgical approach and the use of platinum-based first-line chemotherapy. However, the difference between the two groups was not statistically significant.


State of the art and development of a drug-drug interaction large scale predictor based on 3D pharmacophoric similarity.
Co-administration of drugs is a primary cause of Adverse Drug Reactions (ADRs) and a drain on the health care industry costing billions of dollars and reducing quality of life. Drug-Drug Interactions (DDIs) account for as much as 30% of all ADRs. Unfortunately, DDIs are not systematically explored pre-clinically and are difficult to detect in post-marketing drug surveillance. For this reason, the detection and prediction of DDIs is an important problem in both drug development and pharmacovigilance. The comparison of the 3D drug structures provides a powerful tool for DDI prediction. In this article, we present the first large scale model for predicting DDIs using the drug's 3D molecular structure. In addition to identifying putative drug interactions we can also isolate the pharmacological or clinical effect associated with the predicted interactions. The model has good performance in two different hold-out validations and in external test sets. We found that the top scored drug pairs were significantly enriched for known clinically relevant interactions and that 3D structure data is providing significantly independent information from other approaches, including 2D structure (p=0.003). We demonstrated the usefulness of the proposed methodology to systematically identify pharmacokinetic and pharmacodynamic interactions, provided an exploratory tool that can be used for patient safety and pre-clinical toxicity screening, and reviewed the state of the art methods used to detect DDIs.


Cells at intermediate oxygen levels can be more important than the "hypoxic fraction" in determining tumor response to fractionated radiotherapy.
The presence of hypoxic cells in human tumors is thought to be one of the principal reasons for the failure of radiation therapy. Intensive laboratory and clinical efforts to overcome tumor hypoxia have focused on oxygenating, radiosensitizing or killing the maximally radioresistant fraction of tumor cells. This "hypoxic fraction" dominates the single-dose radiation response, irrespective of the oxygenation status of the remainder of the tumor cell population. However, at doses that are typical of those delivered in a daily radiotherapy protocol, we show that the tumor response is highly dependent upon the cells at oxygen levels intermediate between fully oxygenated and hypoxic (0.5-20 mm Hg). For most tumors, these cells are more important than the radiobiologically hypoxic cells in determining treatment outcome after 30 fractions of 2 Gy. We also show that under conditions of diffusion-limited hypoxia, the impact of full reoxygenation between fractions is much smaller than previously realized. Together, the results imply that tumor hypoxia plays a more significant role in determining the outcome of fractionated radiotherapy than previous measurements and assumptions of hypoxic fractions have indicated. Therefore, the concept of a hypoxic fraction in human tumors is less meaningful when pertaining to a fractionated radiotherapy regimen, and should not be expected to be useful for predicting tumor responses in the clinic. This implies the need to characterize tumor oxygenation in a manner that reflects the true oxygenation status of all the tumor cells, not just the ones most refractory to the effects of ionizing radiation. Furthermore, effective therapeutic agents must have the ability to specifically sensitize or kill those cells at intermediate levels of oxygen in addition to the radiobiologically hypoxic cells.


A skin in situ immune cell detection kit for the diagnosis and classification of cutaneous lupus erythematosus.
Although lupus can be diagnosed by first impression, medical history, physical examination, pathological analysis and laboratory tests, the accurate classification of cutaneous lupus erythematosus (LE) is still a major challenge in the clinic, which might mislead the selection of treatments and miss the right time for the administration of therapies. The goal of this study was to establish a novel kit to assist with the diagnosis and classification of cutaneous lupus. Sixty-five patients from three hospitals were included in this study, including 50 patients with LE and other similar skin diseases. We invited two dermatology specialists to make an accurate diagnosis of the subtypes of lupus based on the patient's clinical features, laboratory examination tests, pathology manifestation analysis, medical treatments and follow-up records. Then, we used their diagnosis results as a standard to which we successively compared the consistency of each step of our diagnosis processes, including impression diagnosis, pathology diagnosis, the combined consideration of the former two diagnostic analyses, and the results of an in situ immune cell detection kit to assist in arriving at a judgement. By Cohen's kappa analysis, we found that the results of the in situ immune cell detection kit had the highest consistency with the diagnoses of the two specialists, both for the diagnosis (k=0.921) and for the classification of cutaneous lupus (k=0.940). In addition, this kit enhanced the LE classification accuracy by 36.3% compared with the diagnostic accuracy of impression diagnosis combined with only pathological analysis. This skin in situ immune cell detection kit may assist doctors in achieving a higher diagnostic performance and price ratio and enhance their diagnostic efficiency.


Obesity increases the risk of UV radiation-induced oxidative stress and activation of MAPK and NF-kappaB signaling.
Obesity has been implicated in several diseases, including cancer; however, the relationship of obesity and susceptibility to ultraviolet (UV) radiation-caused skin diseases has not been investigated. As UV-induced oxidative stress has been implicated in several skin diseases, we assessed the role of obesity on UVB-induced oxidative stress in genetically obese Lep(ob)/Lep(ob) (leptin-deficient) mice. Here, we report that chronic exposure to UVB (120 mJ/cm(2)) resulted in greater oxidative stress in the skin of obese mice in terms of higher levels of H(2)O(2) and NO production, photo-oxidative damage of lipids and proteins, and greater depletion of antioxidant defense enzymes, like glutathione, glutathione peroxidase, and catalase. As UV-induced oxidative stress mediates activation of MAPK and NF-kappaB signaling pathways, we determined the effects of UVB on these pathways in obese mice. Exposure of obese mice to UVB resulted in phosphorylation of ERK1/2, JNK, and p38 proteins of the MAPK family. Compared to wild-type mice, the obese mice exhibited higher levels of phosphorylation of these proteins, greater activation of NF-kappaB/p65, and higher levels of circulating proinflammatory cytokines, including TNF-alpha, IL-1beta and IL-6, on UVB irradiation. Taking these results together, our study suggests for the first time that obesity in mice is associated with greater susceptibility to UVB-induced oxidative stress and therefore may be a risk factor for skin diseases associated with UVB-induced oxidative stress.


Antigen-dependent and -independent proliferative T-cell populations in the peritoneal exudate cells of immunized mice.
In vitro proliferative responses of T lymphocytes in the peritoneal exudate cells of C3H/HeN(Iak) mice immunized with horse red blood cells (HRBC) were examined by determining the uptake of tritiated thymidine [( 3H]TdR) into the cells. Although the cells showed a basal proliferative response in the absence of antigen, addition of specific antigen increased the response sharply. Both the basal response and that stimulated by antigen disappeared if the cells had been previously treated with complement and anti-Iak antibody (AIak), anti-MAC-1 antibody (AMAC-1) or anti-Thy-1 antibody, but not anti-Ig antibody. Adding macrophages prepared from the peritoneal exudate cells of normal mice to AMAC-1-treated T-cell (i.e. Iak+ plus Iak- T-cell) cultures restored both of the responses, while adding them to AIak-treated T cells (i.e. Iak- T cells) only restored the antigen-specific response. These findings indicate that the basal proliferation is due to or dependent on the proliferation of Iak+ T cells, while the antigen-specific response is mainly due to Iak- T cells. Furthermore, interleukin (IL)-2 production was also examined. Immune T cells produced some IL-2 in the absence of antigen. The production by AMAC-1- or AIak-treated cells was impaired, but adding macrophages to the AMAC-1-treated cell cultures restored production. This result also suggests that the mode of IL-2 production by the Iak+ and Iak- cells is different. Proliferative responses of AMAC-1- or AIak-treated T cells to IL-2 were also examined. The AIak-treated cells dose-dependently responded to IL-2, while the response of Iak+ cells, which could be estimated by subtracting the response of AIak-treated cells from that of AMAC-1-treated cells, did not depend on the doses. These results indicate that in the immune peritoneal exudate the Iak+ T cells are functionally different from Iak- T cells.


Use of laparoscopy in pediatric urology.
The goal of laparoscopy is to minimize patient morbidity while maintaining successful outcomes. The use of laparoscopy in urology has grown significantly over the past 30 years. Its use has been slower to gain acceptance in pediatrics than in the adult population. Laparoscopic orchidopexies and nephrectomies are commonly performed and have become widely accepted as alternatives to open surgery, if not the gold standard. The more technically demanding procedures, such as laparoscopic pyeloplasty, laparoscopic-assisted bladder reconstruction, and laparoscopic ureteral reimplantation, tend to be performed at selected centers and have yet to achieve widespread acceptance. As laparoscopy is applied more widely in pediatric urology, its potential benefits and drawbacks will be clarified.


Analytical and numerical study of particles with binary adsorption.
Electro-oxidation of ethanol represents a key process in fuel-cell technology. We introduce a generalization of the random sequential adsorption model to study the long time scale and large length scale properties of the electro-oxidation process. We provide an analytical solution for one dimension and Monte Carlo results in two dimensions. We characterize the coverage and percolation properties of the jammed state and unveil the influence of quenched impurities in the selectivity of oxidation products.


Equations for predicting height for elderly Mexican Americans are not applicable for elderly Mexicans.
Common indices for the assessment of nutritional status take height into account. Elderly individuals are frequently unable to assume the position needed for this measurement. Therefore, equations have been developed for predicting height in elderly American Whites, American Blacks, and Mexican Americans using knee height as a predictor. These equations may not be applicable for the elderly in other populations. A sample of 736 individuals was studied (186 males, 550 females) with a mean age of 74.7 +/- 8 years. Height and knee height (without shoes) were measured in millimeters. Multiple regression and cross-validation was performed. The correlation between knee height and standing height was similar in women (r = 0.86; P < 0.0001) and men (r = 0.83; P < 0.0001). The equations obtained were as follows: men (height in cm) = 52.6 + (2.17 x knee height in cm) and women (height in cm) = 73.7 + (1.99 x knee height in cm) - (0.23 x age in years). Cross-validation showed that the pure error was less than the root mean square error (RMSE) in both sexes. Mean heights, based on the equations of Chumlea et al. (1998) for Mexican Americans significantly differ from the reference values for females and males. Therefore, the equations developed by Chumlea et al. (1998) for elderly Mexican Americans do not appear to be applicable for elderly Mexicans.


Extracorporeal membrane oxygenation to support whole-lung lavage in pulmonary alveolar proteinosis: salvage of the drowned lungs.
Pulmonary alveolar proteinosis is a rare lung disease characterized by accumulation of lipoproteinaceous material within the alveoli. Therapeutic whole-lung lavage (WLL) under general anesthesia is the standard treatment in patients with progressive symptomatic disease. Severe hypoxemic respiratory failure is uncommon, yet when present poses a technical challenge to performing WLL without further compromising respiratory status. Rarely, hyperbaric chamber or extracorporeal membrane oxygenation (ECMO) has been utilized to perform WLL to manage severe hypoxemia, with venovenous ECMO being used more often. We present a case of hypoxemic and hypercarbic respiratory failure from pulmonary alveolar proteinosis successfully managed by placing the patient on venoarterial ECMO to facilitate the performance of bilateral WLL.


Reoperative surgery for persistent hyperparathyroidism.
Persistent hyperparathyroidism is an uncommon but recognized sequela of hyperparathyroidectomy that presents difficult diagnostic and surgical challenges. The approach to such patients, particularly in the area of localizing procedures and the conduct of surgery, is reviewed. The successful management of patients with persistent hyperparathyroidism is directly proportional to the surgeon's depth of experience with this entity.


Hyperoxia-Induced ΔR1: MRI Biomarker of Histological Infarction in Acute Cerebral Stroke.
To evaluate whether hyperoxia-induced ΔR1 (hyperO2ΔR1) can accurately identify histological infarction in an acute cerebral stroke model. In 18 rats, MRI parameters, including hyperO2ΔR1, apparent diffusion coefficient (ADC), cerebral blood flow and volume, and 18F-fluorodeoxyglucose uptake on PET were measured 2.5, 4.5, and 6.5 hours after a 60-minutes occlusion of the right middle cerebral artery. Histological examination of the brain was performed immediately following the imaging studies. MRI and PET images were co-registered with digitized histological images. The ipsilateral hemisphere was divided into histological infarct (histological cell death), non-infarct ischemic (no cell death but ADC decrease), and non-ischemic (no cell death or ADC decrease) areas for comparisons of imaging parameters. The levels of hyperO2ΔR1 and ADC were measured voxel-wise from the infarct core to the non-ischemic region. The correlation between areas of hyperO2ΔR1-derived infarction and histological cell death was evaluated. HyperO2ΔR1 increased only in the infarct area (p ≤ 0.046) compared to the other areas. ADC decreased stepwise from non-ischemic to infarct areas (p = 0.002 at all time points). The other parameters did not show consistent differences among the three areas across the three time points. HyperO2ΔR1 sharply declined from the core to the border of the infarct areas, whereas there was no change within the non-infarct areas. A hyperO2ΔR1 value of 0.04 s-1 was considered the criterion to identify histological infarction. ADC increased gradually from the infarct core to the periphery, without a pronounced difference at the border between the infarct and non-infarct areas. Areas of hyperO2ΔR1 higher than 0.04 s-1 on MRI were strongly positively correlated with histological cell death (r = 0.862; p < 0.001). HyperO2ΔR1 may be used as an accurate and early (2.5 hours after onset) indicator of histological infarction in acute stroke.


Mouse fetal thymus lobes cultured in IL-2 generate CD3+, TCR-gamma delta-expressing CD4-/CD8+ and CD4-/CD8- cells.
Whole, undisrupted, 14-day fetal mouse thymus lobes were liquid-cultured in medium supplemented with 10 U/ml rIL-2. The cells that emerged from these fetal thymus lobes grew in an IL-2-dependent manner and showed non-MHC-restricted cytolytic activity. By two-color flow microfluorimetric analysis they could be subdivided into CD4-/CD8+ and CD4-/CD8- subpopulations, both of which contained CD3+ cells. Northern analysis of total cellular RNA revealed full-length transcripts of gamma- and delta-message, predominantly the truncated (1.0 kb) beta- and no detectable alpha-message. Taken together, these results show that by culturing 14-day fetal thymus lobes in IL-2, in the absence of deliberate mitogen stimulation, CD3+, TcR-gamma delta-expressing CD4-/CD8+ and CD4-/CD8- T cells are obtained. Such cells may represent the precursors of similar cells found outside the thymus in adult mice.


Projective-anticipating, projective, and projective-lag synchronization of time-delayed chaotic systems on random networks.
We study projective-anticipating, projective, and projective-lag synchronization of time-delayed chaotic systems on random networks. We relax some limitations of previous work, where projective-anticipating and projective-lag synchronization can be achieved only on two coupled chaotic systems. In this paper, we realize projective-anticipating and projective-lag synchronization on complex dynamical networks composed of a large number of interconnected components. At the same time, although previous work studied projective synchronization on complex dynamical networks, the dynamics of the nodes are coupled partially linear chaotic systems. In this paper, the dynamics of the nodes of the complex networks are time-delayed chaotic systems without the limitation of the partial linearity. Based on the Lyapunov stability theory, we suggest a generic method to achieve the projective-anticipating, projective, and projective-lag synchronization of time-delayed chaotic systems on random dynamical networks, and we find both its existence and sufficient stability conditions. The validity of the proposed method is demonstrated and verified by examining specific examples using Ikeda and Mackey-Glass systems on Erdos-Renyi networks.


The Role of Immune Checkpoint Inhibitors in the Treatment of Extensive-Stage Extrapulmonary Small Cell Carcinoma.
Small cell carcinoma is a type of highly aggressive poorly differentiated neuroendocrine tumor that can arise from multiple organs, including but not limited to bronchial tissue, pancreas, gastrointestinal tract, and genitourinary system. The most commonly studied type is small cell lung cancer (SCLC) which carries the worst prognosis among lung cancers. After multiple promising clinical trials, the National Comprehensive Cancer Network has recently added atezolizumab and durvalumab in combination with platinum-based chemotherapy/etoposide to the first-line treatment regimen for extensive-stage SCLC (ES-SCLC). Meanwhile, the recommended treatment for extrapulmonary small cell carcinoma (EPSCC) remains unchanged. In this review, we try to explore the role of immunotherapy in the treatment of EPSCC.


The validity of the University of Waterloo Colored Dot Test for Color Vision Testing in adults and preschool children.
Most color vision tests require a high level of cognitive ability and as such are problematic for preschool children and multiply challenged individuals. Our goal was to design a color vision test for these groups and evaluate the clinical utility for preschool children. The University of Waterloo Colored Dot Test (UWCDot) for Color Vision Testing requires the subject to distinguish a colored disc from seven gray discs. The target disc was a Munsell color along the deutan, protan, or tritan confusion line with gray. The first phase estimated the sensitivity and specificity of the test for adults. Thirty-one adults with normal color vision and 21 adults with congenital red-green defects participated. In the second phase, the utility of the UWCDot test for screening preschool children was determined. Subjects were 281 males and 269 females aged 2.5 to 5 years with normal vision. Their color vision was also assessed with the Standard Pseudoisochromatic Plates, Part 1 (SPP1). The sensitivity and specificity of UWCDot for adults approached the values for the desaturated D-15 when subjective responses were scored. Monitoring fixational eye movements produced sensitivity and specificity values that were similar to the anomaloscope. After adjusting the scoring criterion for the preschool children by using the females as a control, 2.9% of the males were identified as red-green deficient, 1.8% were blue-yellow deficient, and 3.2% had an unclassified deficiency. By definition, 1% of the females failed the test. Counting fixational eye movements was not a useful scoring method in the preschool children. Comparisons with SPP1 indicated that the UWCDot uncovers approximately 35% of the individuals with definite red-green color vision defects. Our results indicate that the UWCDot is capable of detecting approximately 35% of the preschool children who have a congenital red-green color vision defect. These individuals are likely to have a more severe deficiency.


Carbohydrate antigens recognized by anti-horseradish peroxidase antiserum are expressed on mammalian cells.
Antiserum raised against horseradish peroxidase (HRP) recognizes neural specific carbohydrate antigens in Drosophila and other insects. The occurrence of the antigens in mammalian cells was investigated. Proteins were extracted from rat pheochromocytoma cells, PC12, and various tissue of rat and bovine origin, and further purified by successive chromatography with Con A-Sepharose and anti-HRP glycopeptide antibody-Sepharose. The proteins were separated by SDS-PAGE and subjected to immunoblot analysis of the antigens. When the Con A- and antibody-Sepharose bound fractions were examined, four glycoproteins with carbohydrate antigens recognized by anti-HRP antiserum were identified in all the tissue. They are low molecular weight glycoproteins that are not membrane-bound. We demonstrated that the carbohydrate antigens recognized by the anti-HRP antibodies are not confined to insects but are expressed on mammalian cells in several tissue.


Assessing the Pathogenicity of Insertion and Deletion Variants with the Variant Effect Scoring Tool (VEST-Indel).
Insertion/deletion variants (indels) alter protein sequence and length, yet are highly prevalent in healthy populations, presenting a challenge to bioinformatics classifiers. Commonly used features--DNA and protein sequence conservation, indel length, and occurrence in repeat regions--are useful for inference of protein damage. However, these features can cause false positives when predicting the impact of indels on disease. Existing methods for indel classification suffer from low specificities, severely limiting clinical utility. Here, we further develop our variant effect scoring tool (VEST) to include the classification of in-frame and frameshift indels (VEST-indel) as pathogenic or benign. We apply 24 features, including a new "PubMed" feature, to estimate a gene's importance in human disease. When compared with four existing indel classifiers, our method achieves a drastically reduced false-positive rate, improving specificity by as much as 90%. This approach of estimating gene importance might be generally applicable to missense and other bioinformatics pathogenicity predictors, which often fail to achieve high specificity. Finally, we tested all possible meta-predictors that can be obtained from combining the four different indel classifiers using Boolean conjunctions and disjunctions, and derived a meta-predictor with improved performance over any individual method.


Route to noise-induced synchronization in an ensemble of uncoupled chaotic systems.
We investigate the route to synchronization in an ensemble of uncoupled chaotic oscillators under common noise. Previous works have demonstrated that, as the common-noise amplitude is increased, both chaotic phase synchronization and complete synchronization can occur. Our study reveals an intermediate state of synchronization in between these two types of synchronization. A statistical measure is introduced to characterize this noise-induced synchronization state and the dynamical origin of the transition to it is elucidated based on the Lyapunov dimension of the set formed by all oscillator states.


Children with adequate academic achievement scores referred for evaluation of school difficulties: information processing deficiencies.
Children (7-11 years old) with standardized academic achievement test scores in the normal range referred for evaluation of learning problems were compared to low-achieving children matched for age, sex, and nonverbal cognitive ability, and to children with no known history of learning difficulty matched for age, sex, and reading (all N = 65) on a battery of computerized tasks of nonverbal information processing. The normally achieving referred children performed similarly to the low-achieving group but worse than reading-matched nonreferred counterparts. These findings suggest that children who struggle in school yet perform adequately on standardized achievement measures can have heightened neurodevelopmental vulnerability. Implications are discussed with respect to the underlying substrate of learning disabilities, as well as their diagnosis, classification, and remediation.


[D-Ala2,NMePhe4,Gly-ol5]enkephalin, but not [D-Pen2,L-Pen5]enkephalin, specifically inhibits behaviors induced by the dopamine D2 agonist RU 24213.
The effects of intracerebroventricular injection (10 microliters) of mu- and delta-selective opioid peptides on behaviors induced by the dopamine D2-selective agonist RU 24213 were investigated in the mouse, using multi-dimensional behavioral analyses. Fifteen to 30 min after the start of behavioral measurements, a 3.0 mg/kg dose of RU 24213 produced a marked increase in linear locomotion, circling, rearing and grooming behaviors. Although the mu-selective opioid peptide [D-Ala2,NMePhe4,Gly-ol5]enkephalin (DAGO) (0.003 and 0.01 microgram) itself did not significantly affect behaviors, DAGO (0.01 microgram) antagonized the RU 24213 (3.0 mg/kg)-induced increase in behaviors such as linear locomotion, circling, rearing, and grooming. Additionally, the effects of DAGO on RU 24213-induced behaviors were fully reversed by treatment with the mu-selective alkylating agent beta-funaltrexamine (beta-FNA) (5.0 micrograms). In contrast, the delta-selective opioid peptide [D-Pen2,L-Pen5]enkephalin (0.3 or 1.0 micrograms) had no marked effects on RU 24213 (3.0 mg/kg)-induced behaviors. These results suggest that mu- but not delta-opioid receptors play an inhibitory role in the behaviors induced by the selective activation of dopamine D2 receptors.