Spatial and temporal expression of transferrin gene in the rat mammary gland.
The distribution and concentration of transferrin mRNA in the rat mammary gland was analyzed using in situ hybridization, and the results were compared with those obtained for other milk protein mRNA. The [35S]RNA probes prepared from rat cDNA for transferrin and for alpha-, beta-, and gamma-caseins, alpha-lactalbumin, and whey acidic protein were used to probe mammary tissue from rats in late pregnancy and at different stages of lactation. The overall level of transferrin gene expression varied in a biphasic manner, decreasing after parturition to barely detectable levels at d 2 to 10 of lactation before increasing again markedly in late lactation. This temporal pattern contrasts sharply with that observed for the other genes, for which levels tended to rise or to remain relatively stable until late lactation. The spatial patterns of transferrin expression were also quite distinct, and, even during the period of low expression, some alveoli showed high concentrations of transferrin mRNA. In contrast, intramammary distribution of mRNA for the other genes was relatively uniform. Our results show that the patterns of transferrin gene expression differ both spatially and temporally from those of five other milk protein genes and suggest that transferrin gene expression is controlled by a regulatory system that turns individual alveoli either fully on or fully off.


Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles.
The impact of dietary patterns and the commensal microbiome on susceptibility to and severity of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been largely ignored to date. In this Perspective, we present a rationale for an urgent need to investigate this possible impact and therapeutic options for COVID-19 based on dietary and microbiome modifications. The mitigating role of nanotechnology with relation to the impact of SARS-CoV-2 virus is highlighted.


An Ultra-Low Power Charge Redistribution Successive Approximation Register A/D Converter for Biomedical Applications.
Power consumption is one of the key design constraints in biomedical devices such as pacemakers that are powered by small non rechargeable batteries over their entire life time. In these systems, Analog to Digital Convertors (ADCs) are used as interface between analog world and digital domain and play a key role. In this paper we present the design of an 8-bit Charge Redistribution Successive Approximation Register (CR-SAR) analog to digital converter in standard TSMC 0.18μm CMOS technology for low power and low data rate devices such as pacemakers. The 8-bit optimized CR-SAR ADC achieves low power of less than 250nW with conversion rate of 1KB/s. This ADC achieves integral nonlinearity (INL) and differential nonlinearity (DNL) less than 0.22 least significant bit (LSB) and less than 0.04 LSB respectively as compared to the standard requirement for the INL and DNL errors to be less than 0.5 LSB. The designed ADC operates at 1V supply voltage converting input ranging from 0V to 250mV.


Insecticide resistance of adults and nymphs of Asian citrus psyllid populations from Apatzingán Valley, Mexico.
Control of the Asian citrus psyllid Diaphorina citri Kuwayama, the most important pest of citrus worldwide, is based on the use of insecticides, though unsatisfactory results have recently been reported. In this study, insecticide resistance of D. citri to three insecticides (bifenthrin, malathion, and chlorpyrifos) was examined. Three populations (designated Dci-CParácuaro, Dci-El Junco, and Dci-Antúnez) of both adults and fourth-instar D. citri individuals were collected in 2014 at two different times and on one occasion, respectively, from three locations (Crucero de Parácuaro, El Junco, and Antúnez). These locations represent the major commercial Mexican lemon production areas in the Apatzingán Valley in the state of Michoacán, Mexico. The three populations of D. citri adults and fourth-instar nymphs at the different collection times showed low levels of resistance (≤7-fold) to bifenthrin, but were very resistant to malathion (≤345- and ≤432-fold for adults and fourth instars, respectively) and chlorpyrifos (≤2435- and ≤1424-fold for adults and fourth instars, respectively). Resistance levels to the tested insecticides were highly variable but homogeneous among seasons and localities. Resistance management programmes that include crop sanitation, use of biological and cultural control practices, and rotation of insecticide classes should be established, particularly in areas where D. citri has developed resistance to malathion and chlorpyrifos. © 2017 Society of Chemical Industry.


IBD and skeletal health: children are not small adults!
Patients with inflammatory bowel disease often have decreased bone mass, and fragility fractures can occur. Multiple disease- and treatment related factors, including malnutrition, inflammation, malabsorption, decreased weight-bearing physical activity, and corticosteroids negatively influence bone metabolic activity. Because low-impact fracture is the pathologic expression of critically reduced bone mass and bone quality, knowing the relative risk of fractures in patients with IBD is of great interest. The absolute risk for incident fractures in these patients is still being debated. Clinical and laboratory research is clarifying mechanisms by which IBD can affect the function of osteoblasts and osteoclasts. In this concise review, we aim to provide an update on this topic, with focus on how pediatric IBD affects bone health.


[Effects of parathyroid hormone on the cardiovascular system].
It has been well accepted that the bone and kidney are the principal organs of parathyroid hormone (PTH) actions, but there has been little work on the cardiovascular system. We evaluated the effect of PTH on the cardiovascular system of rats. In thiobutabarbital anesthetized rats, synthetic bovine parathyroid hormone, containing the amino acid (b-PTH 1-34) in dose of 0.1-10 micrograms/kg iv, caused dose related decrease in mean arterial blood pressure (MAP). On the other hand, there were significantly increase in heart rate (HR) and left ventricular contractile force. With the doses of 10 micrograms/kg, PTH decreased the MAP from 104.3 to 55.5 mmHg, left ventricular pressure (LVP) 122.1 to 96.4 mmHg, left ventricular end diastolic pressure (LVEDP) from 6.70 to 6.37 mmHg and LV dp/dt max 5,684 to 4,736 mmHg/sec. The HR, LV dp/dt/p and Vmax increase from 399.7 to 410.0 bpm, 95.5 to 108.4/sec, 98.2 to 107.4/sec, respectively. The propranolol, phentolamine, atropine and promethazine did not affect these actions of PTH. On the basis of these findings, we conclude that PTH has the directory vasodepressive action and the effect of augmentation of the left ventricular contractile force.


Gene regulation knowledge commons: community action takes care of DNA binding transcription factors.
A large gap remains between the amount of knowledge in scientific literature and the fraction that gets curated into standardized databases, despite many curation initiatives. Yet the availability of comprehensive knowledge in databases is crucial for exploiting existing background knowledge, both for designing follow-up experiments and for interpreting new experimental data. Structured resources also underpin the computational integration and modeling of regulatory pathways, which further aids our understanding of regulatory dynamics. We argue how cooperation between the scientific community and professional curators can increase the capacity of capturing precise knowledge from literature. We demonstrate this with a project in which we mobilize biological domain experts who curate large amounts of DNA binding transcription factors, and show that they, although new to the field of curation, can make valuable contributions by harvesting reported knowledge from scientific papers. Such community curation can enhance the scientific epistemic process.Database URL: http://www.tfcheckpoint.org.


Leiomyosarcoma of the duodenum in a 10-year-old boy.
An unusual incidence of a duodenal leiomyosarcoma in a 10-year-old boy is presented. The corrected diagnosis was made after a 27-month course of occult gastrointestinal bleeding, vague abdominal complaints, and anemia. Gastrointestinal radiography and upper gastrointestinal endoscopy were useful in localizing the lesion. The tumor was removed at exploratory surgery by simple excision. On frozen section, the tumor was thought to be benign, but fixed microscopic histological sections revealed a well-differentiated, malignant smooth muscle tumor. The presentation of this tumor in a child is compared to previously reported cases in adults, and the biological and clinical characteristics of malignant smooth muscle tumors of the gastrointestinal tract are reviewed.


Molecular genetics in basic myology: a rapidly evolving perspective.
Myology has greatly benefited from the recent unification of concepts in molecular, cellular, and developmental biology. The interplay between intrinsic and extrinsic factors in determining the physiologic characteristics of individual myofibers has emerged as an important theme. Of special note is the manner in which the study of contractile protein gene structure and expression has contributed to our understanding of the development and ultimate plasticity of the contractile apparatus. As mechanistic models of normal myogenesis achieve increasing sophistication, the opportunities for understanding the pathogenesis of progressive muscle disfunction improve. In this article we review recent progress in basic myology which will be of interest to clinicians studying the heritable neuromuscular disorders.


An incomplete picture: challenges of partial biopsies in large diameter atypical melanocytic lesions.
Large diameter atypical pigmented lesions (LDAPL) can be challenging to diagnose accurately using partial biopsies because of pathologic heterogeneity, while at the same time large excisions of these lesions confer significant morbidity to patients. Consequently, clinicians are often challenged by the management of these lesions. In this case, we describe an elderly patient with a history of multiple basal cell carcinomas, prior melanomas, and a family history of melanoma who presented with an irregularly pigmented brown and dark brown patch on his upper back. This lesion was evaluated with multiple partial incisional biopsies from the most atypical appearing areas of the lesion identified on dermoscopy, each showing mild and moderate atypical melanocytes. However, the patch continued to change clinically and eventually the patient underwent a 5mm wide local excision, which revealed severely atypical melanocytic proliferation with areas consistent with melanoma in situ. This case highlights the need for clinicians to lower their threshold for excisional biopsy of LDAPL in high-risk patients.


A Longitudinal Study of Cognitive Risks for Depressive Symptoms in Children and Young Adolescents.
Youths with high (N = 52) or low cognitive vulnerability (N = 48) for depression were selected from a larger sample (N = 515) of students (7-10 years old), based on their attributional style (AS), negative cognitions (NC), and/or self-competence (SC). Long-term effects of cognitive vulnerabilities on depressive symptoms were examined in a 3-year, three-wave, multiinformant, longitudinal design. Three findings emerged. First, some empirical overlap exists among these three types of cognitive diatheses, especially between NC and SC. Second, the combination of AS, NC, and SC had a significant (but diminishing) relationship to depressive symptoms at 6, 18, and 30 months, primarily due to NC and SC, not AS. Third, interactions between cognitive risk and life events were not significant, suggesting an additive type of diathesis-stress model for depression in young adolescents.


[Early detection of lung cancer. Possibilities--limits--organization].
The aim of early detection of lung cancer is to detect patients in a resectable stage. Immunological methods don't solve this problem as yet. The only procedure which has some efficiency now, is the control of risk groups by periodic chest radiography. The improvement of the screening modalities is proposed. The development of sputum cytology for early detection of lung tumors with central localization is a problem of high research priority.


On the method of revealing enamel structure by acid etching. Aspects of optimization and interpretation.
The study aimed at finding an optimal combination of acid concentration and etching time when nitric acid is used as etchant for the study of the finer details of human dental enamel structure. Four hundred 2-3-mm-thick segments of facio-lingually sectioned human third molar crowns were assigned to 20 groups with 20 specimens in each group, each group differing with respect to acid concentration (0.1, 1, 2.5, and 5%) and etching time (15, 30, 45, 90, and 180 s). After etching and preparation, specimens were observed in the scanning electron microscope (SEM). Surface roughness/topography increased with increasing acid concentration and increasing etching time, but not in a linear fashion; generally, prisms tended to go from flat-surfaced to cone-shaped and prism sheaths from fissure-like to wedge-shaped. Intragroup variations and intergroup similarities were considerable. The two major enamel factors determining the etch effect are crystal orientation and prism sheath properties. Other factors, such as distribution of porosities and crystal quality, also contribute probably. Slight to moderate topography is best for observing the finer enamel structure, for example, etching with concentrations in the range 0.1-1% and with etching times in the range 15-90 s, the stronger the acid, the shorter the time. The depth effect of nitric acid is judged to be relatively small. Considerable variations in expression of prism cross-striations were observed. SEM observations of acid-etched enamel in carefully selected planes are a powerful method for the study of enamel structure, bearing in mind the artifactual aspects of the observed surface.


Ago2 and GW182 expression in mouse preimplantation embryos: a link between microRNA biogenesis and GW182 protein synthesis.
MicroRNA-mediated RNA interference appears to play a role in early development and differentiation processes in preimplantation embryos. However, the expression of its key effectors, including Ago2, a key component of the RNA-induced silencing complex, and GW182, a critical component of GW bodies (GWBs), has not been assessed in preimplantation embryos. To characterise the roles of Ago2 and GW182 in early embryo development, we determined their transcription and protein synthesis in mouse embryos. Transcript levels of Ago2 and GW182 increased steadily from the one-cell stage through to the blastocyst stage when data were not normalised against an internal reference. However, when normalised against the internal standard, transcript levels for both genes were highest in four-cell stage embryos and decreased steadily through to the blastocyst stage. Indirect immunocytochemistry showed that both AGO2 and GW182 proteins were expressed in each stage in the early embryo and were observed to colocalise in the morula and blastocyst stages. Specific silencing of mRNA expression by short interference (si) RNA against Ago2 or Dicer1 decreased the expression of selected apoptosis- and development-related microRNAs, but did not inhibit development up to the blastocyst stage. However, transcription levels of Oct3/4, Nanog and Sox2 were decreased in both Ago2- and Dicer1-knockdown embryos at the blastocyst stage. Furthermore, although knockdown of these genes did not change transcript levels of GW182, GW182 protein synthesis was decreased in blastocyst stage embryos. These results suggest that Ago2 and Dicer1 regulate GW182 protein expression in mouse embryos, which is linked to microRNA biogenesis and likely to be important for differentiation in the blastocyst stage.


The association between glucose fluctuation with sarcopenia in elderly patients with type 2 diabetes mellitus.
Growing evidence shows that sarcopenia is more prevalent in patients with type 2 diabetes mellitus (T2DM) than in the normal population. However, currently, data on the relationship between blood glucose fluctuation and sarcopenia in elderly patients with T2DM are still limited. In this study, 280 patients ≥ 60 years with T2DM were divided into sarcopenic group and non-sarcopenic group, according to the diagnostic criteria of the 2019 Asian Working Group for Sarcopenia. They wore MeiQi to acquire the indexes including time in range (TIR), time above range (TAR), time below range (TBR), mean amplitude of glycemic excursion (MAGE), coefficient of Variation (CV), blood glucose standard deviation (SD), largest amplitude of glycemic excursions (LAGE) and mean glucose (MG). The prevalence rate of sarcopenia was statistically analyzed and the different indicators of glucose fluctuation between the two groups were compared. We analyzed the indexes of glucose fluctuation and appendicular skeletal muscle mass index (ASMI), handgrip strength, the time of five times sit to stand test (FTSST) with Spearman's correlation analysis. Logistic regression was used to analyze the influence factors for sarcopenia. The prevalence of sarcopenia was 15.36%. TIR, MG and TAR were correlated with ASMI, handgrip strength, the time of FTSST. MG and TAR were risk factors for sarcopenia, while TIR was the protective factor of sarcopenia. After adjusting mixing factors, logistic regression analysis showed that TIR was an independent protective factor. The result of the Chi-square test showed that the incidence of sarcopenia in different TIR ranges was different: the proportion of patients with sarcopenia was 40.48% (TIR ≤50%), 20.41% (50%<TIR≤70%) and 8.47% (TIR >70%). TIR is associated with sarcopenia in elderly T2DM patients. Furtherly, the incidence rate of sarcopenia decreases with the increase of TIR.


[Damage photosensitized by chlorine e6 in bacteria with various defects of the DNA repair system].
The goal of the work was to study the sensitivity of isogenic Escherichia coli cells differing in their ability to mediate DNA repair steps to the action of visible light sensitized by chlorine e6. Cells incapable of excision repair as well as those deficient in post-replicative recombination DNA repair were found to be much more sensitive to the combined action of visible light and chlorine e6 as compared to cells whose genes responsible for DNA repair were not damaged. The results indicate that visible light damages bacterial DNA in the presence of chlorine e6.


MRBENet: A Multiresolution Boundary Enhancement Network for Salient Object Detection.
Salient Object Detection (SOD) simulates the human visual perception in locating the most attractive objects in the images. Existing methods based on convolutional neural networks have proven to be highly effective for SOD. However, in some cases, these methods cannot satisfy the need of both accurately detecting intact objects and maintaining their boundary details. In this paper, we present a Multiresolution Boundary Enhancement Network (MRBENet) that exploits edge features to optimize the location and boundary fineness of salient objects. We incorporate a deeper convolutional layer into the backbone network to extract high-level semantic features and indicate the location of salient objects. Edge features of different resolutions are extracted by a U-shaped network. We designed a Feature Fusion Module (FFM) to fuse edge features and salient features. Feature Aggregation Module (FAM) based on spatial attention performs multiscale convolutions to enhance salient features. The FFM and FAM allow the model to accurately locate salient objects and enhance boundary fineness. Extensive experiments on six benchmark datasets demonstrate that the proposed method is highly effective and improves the accuracy of salient object detection compared with state-of-the-art methods.


Absence of an anaphylactic vasopermeability mechanism for immune complex deposition in the Heymann nephritis of rats.
The existence of an anaphylactic mechanism favouring the deposition of circulating immune complexes in Heymann's nephritis and its possible inhibition by disodium cromoglycate (DSCG) and antihistamines was studied. No animal produced anti-renal tubular anaphylactic antibodies (IgE and IgGa classes) and no histamine and PAF (platelet-activating factor) release were obtained when buffy coat cells (BCC) were challenged with the soluble Fx1A antigenic fraction. However, PAF was obtained from phagocytozing leucocytes. Total histamine after boiling 10(7) BCC was less than 20 ng. The frequency of nephritis and quantity of immune deposits in the glomerular basement membrane were similar in treated and control groups. Our results show that, contrary to the data obtained in acute serum sickness of rabbits, an anaphylactic mechanism in Heymann's nephritis does not seem to exist. Accordingly the treatment with antihistamines and/or disodium cromoglycate did not produce any beneficial effect upon the course of the disease.


Differential diagnosis of infantile choledochal cyst with or without biliary atresia.
The choledochal cyst, a cystic dilatation of the biliary tree, in infancy may be associated with biliary atresia (BACH) or without biliary atresia (CH). Infants in both groups usually have similar clinical symptoms at presentation but different management and prognosis. We retrospectively identified 29 infants, aged younger than 1 year, who had surgically proven choledochal cysts from 1991 to 2004. They were diagnosed as CH in 18 patients and BACH in eleven. They had undergone preoperative abdominal ultrasonography (29 patients) and intravenous radionuclide cholangiography (IVRC) (19 patients). The comparison of the clinical characteristics and laboratory examinations between the two groups showed that BACH patients had no sex predominance contrasting to female predominance in CH patients, more often presented with prolonged jaundice and clay-colored stool, and had higher bilirubin levels. In diagnosing BACH by ultrasonography, using the diameter of the extrahepatic cystic dilatation < or =1.5 cm but not atretic gallbladder further increased the sensitivity, specificity, positive and negative predictive rates (81.8%, 100%, 100%, 90% vs 54.5%, 88.8%, 75%, 76.2%, respectively), yielding an increased diagnostic accuracy (93.1% and 75.9%, respectively). In diagnosing BACH by IVRC, the sensitivity, specificity, positive and negative predictive value and diagnostic acCuracy were 100%, 70%, 75%, 100% and 84.2%, respectively. We concluded that there were clinical and laboratory discrepancies between the two groups, including female predominance, prolonged jaundice, clay-colored stool, bilirubin levels and size of cyst. In diagnosing BACH, the accuracy of abdominal ultrasonography will be increased if we use the diameter of the extrahepatic cystic dilatation < or = l.5 cm but not atretic gallbladder as one of the diagnostic cretia. Hepatobiliary scintigraphy had less diagnostic accuracy than ultrasonography but can be added to exclude the diagnosis of BACH.


Targeting astrocytes in major depression.
Astrocytes represent a highly heterogeneous population of neural cells primarily responsible for the homeostasis of the CNS. Astrocytes express multiple receptors for neurotransmitters, including the serotonin 5-HT2B receptors and interact with neurones at the synapse. Astroglia contribute to neurological diseases through homeostatic response, neuroprotection and reactivity. In major depression, astrocytes show signs of degeneration and are decreased in numbers, which may lead to a misbalance in neurotransmission and aberrant synaptic connectivity. In this review, we summarize astroglia-specific effects of major antidepressants and outline future strategies for astroglia-specific therapy in neuropsychiatric disorders.


Mechanisms of action of nonglucose insulin secretagogues.
Insulin release induced by nonglucose secretagogues is initiated from beta-cell by a wide variety of stimuli through specific receptors or binding sites. Activation of receptors in turn generates or enhances the cytosol levels of cAMP, cADPR, IP3, DAG, and AA. These second messengers then activate protein kinases, change the ion currents cross the cell membrane, and mobilize intracellular Ca2+, thereby increasing phosphorylated proteins in the cytosol and augmenting [Ca2+]i. These events trigger exocytotic discharge of insulin. The crucial steps in receptor-mediated stimulation-secretion coupling and their relationship to glucose-stimulated insulin release is summarized in Figure 1. At the present stage of research, the general processes of secretagogue binding to receptors, of generating second messengers, of activating several types of protein kinase, and of altering the membrane potential as well as cytosol calcium levels has been intensively studied and qualitatively clarified. However, we know little about the exact nature of substrates of different protein kinases and their function in the insulin secretion process. With the help of molecular biology and protein chemistry, we expect that this gap will be filled in the near future.


Improvement of Perioperative Outcomes in Major Gynecological and Gynecologic-Oncological Surgery with Hemostatic Gelatin-Thrombin Matrix.
To assess the impact of the use of intraoperative hemostatic gelatin-thrombin matrix (HM) (Floseal®, Baxter Healthcare) on transfusion rates and short-term perioperative outcomes in gynecological surgery. In this retrospective, single-center study, we evaluated data of 215 patients (83 cases and 132 controls) undergoing extensive gynecological surgery (e.g. oncological procedures) with and without intraoperative HM application. Cases and controls did not differ according to age, preoperative hemoglobin (Hb) concentration, and Hb or C-reactive protein (CRP) levels at discharge. Patients receiving HM had significantly reduced operative (168 vs. 199 min, p=0.02) and hospitalization (9 vs. 14 days, p<0.001) times. The mean postoperative Hb drop (3.33 vs. 4.51 g/dl, p<0.001), and the mean postoperative increase in CRP (94.9 vs. 149.1 mg/l, p<0.001) were significantly less pronounced within the HM group. Despite more prevalent coagulopathy (48 vs. 31%, p=0.02), e.g. due to anticoagulant use (15.7 vs. 3%, p<0.001), patients treated using HM needed less frequent transfusions of packed red blood cells [odds ratio (OR)= 0.13, 95% confidence interval (CI)=0.07-0.24) and fresh frozen plasma (OR=0.51, 95% CI=0.24-1.05). In comparison to controls, the need for surgical revisions (OR 0.1, CI 95% 0.02-0.42) and intensive-care unit admissions (OR 0.15, 95% CI=0.08-0.30) was lower in patients treated with HM. To our knowledge, our study is the largest case-control study focusing on Floseal® use in gynecology. The use of HM was associated with significantly better short-term perioperative outcomes. Due to its local action, HM seems to be particularly useful in patients in which anticoagulant medication cannot be paused.


Surgical techniques for evacuation of chronic subdural hematoma: a mini-review.
Chronic subdural hematoma is one of the most common neurosurgical pathologies with over 160,000 cases in the United States and Europe each year. The current standard of care involves surgically evacuating the hematoma through a cranial opening, however, varied patient risk profiles, a significant recurrence rate, and increasing financial burden have sparked innovation in the field. This mini-review provides a brief overview of currently used evacuation techniques, including emerging adjuncts such as endoscopic assistance and middle meningeal artery embolization. This review synthesizes the body of available evidence on efficacy and risk profiles for each critical aspect of surgical technique in cSDH evacuation and provides insight into trends in the field and promising new technologies.


An evidence-based cesarean section suggested for universal use.
This article suggests a unified way to perform Cesarean sections. Even in the same departments, different modifications are in use. Therefore, one cannot rely on the early or late outcome of the procedure as long as all the surgical steps are not standardized. The Misgav Ladach (Stark) Cesarean Section presented here is an evidence-based operation. Its basic principles are a modified Joel-Cohen abdominal incision, one-layer continuous suturing of the uterus using a big needle, leaving peritoneum open, closing fascia continuously and a few Donati skin sutures. This method has been subjected to scores of comparative studies with other methods in use, proving its advantages over them concerning duration, blood loss, febrile morbidity, need for analgesics, and costs. It is suggested that this method should be used as the standardized universal method which will enable comparison between obstetricians and institutions, and offer the parturient the best possible outcome.


Electrophoretic injection within microdevices.
The flexibility of the microfabricated format creates unique opportunities for study of the electrophoretic process. The present work utilizes digital images to capture the motion of DNA samples during pre-electrophoretic processes. A systematic study of DNA loading and strong sample stacking (sample concentration effects) was performed in order to analyze realistic DNA analysis conditions within microdevices. Using digital imaging and microscopy, DNA sample profiles within the injector were analyzed by deconvolving the geometrical intensity profile into different velocity groups. This analysis illustrates the evolution of molecular separation into distinct migrating populations within the injector itself. The present study performed DNA injections within microfabricated devices imposing run voltages between 85 and 850 V/cm. Data from 3 different offset lengths of a double-T cross-injector, 10 different applied voltages, and 2 different sample preparation protocols are presented.


The faith, activity, and nutrition (FAN) program: design of a participatory research intervention to increase physical activity and improve dietary habits in African American churches.
African Americans are at increased risk for cardiovascular disease and cancer morbidity and mortality. Physical activity and healthy dietary practices can reduce this risk. The church is a promising setting to address health disparities, and community-based participatory research is a preferred approach. Using a community-based participatory approach and the social ecologic model, the FAN trial aims to increase self-reported moderate-intensity physical activity and fruit and vegetable consumption and reduce blood pressure in African American church members. Secondary aims are to increase objectively measured moderate-intensity physical activity and fiber/whole grain consumption and reduce fat consumption. FAN is a group randomized trial (GRT) with two levels of clustering: participants (N=1279; n=316 accelerometer subgroup) within church and church within church cluster. In the first wave, seven clusters including 23 churches were randomized to an immediate intervention or delayed intervention. In subsequent waves, 51 churches were randomized to an immediate or delayed intervention. Church committee members, pastors, and cooks participate in full-day trainings to learn how to implement physical activity and dietary changes in the church. Monthly mailings and technical assistance calls are delivered over the 15-month intervention. Members complete measurements at baseline and 15 months. A detailed process evaluation is included. FAN focuses on modifying the social, cultural, and policy environment in a faith-based setting. The use of a community-based participatory research approach, engagement of church leaders, inclusion of a detailed process evaluation, and a formal plan for sustainability and dissemination make FAN unique.


The effects of fungal volatile organic compounds on bone marrow stromal cells.
Evidence has shown that individuals exposed to indoor toxic molds for extended periods of time have elevated risk of developing numerous respiratory illnesses. It is not clear at the cellular level what impact mold exposure has on the immune system. Herein, we show that 2 fungal volatiles (E)-2-octenal and oct-1-en-3-ol have cytotoxic effects on murine bone marrow stromal cells. To further analyze alterations to the cell, we evaluated the impact these volatile organic compounds have on membrane composition and hence fluidity. Both (E)-2-octenal and oct-1-en-3-ol exposure caused a shift to unsaturated fatty acids and lower cholesterol levels in the membrane. This indicates that the volatile organic compounds under investigation increased membrane fluidity. These vast changes to the cell membrane are known to contribute to the breakdown of normal cell function and possibly lead to death. Since bone marrow stromal cells are vital for the appropriate development and activation of immune cells, this study provides the foundation for understanding the mechanism at a cellular level for how mold exposure can lead to immune-related disease conditions.


Increased Serum Klotho With Age-Related Aortic Stiffness and Peripheral Vascular Resistance in Young and Middle-Aged Swine.
The anti-aging function of Klotho gene has been implicated in age-related diseases. The physiological importance of Klotho in the progression of arterial stiffness with aging, however, remains unclear. The goal of this study is to determine the correlation of circulating Klotho with early age-related aortic stiffening and peripheral hemodynamics. We measured serum Klotho levels in a group of pigs with age ranges of 1.5-9 years and investigated the relationship between Klotho levels and biomarkers of aortic stiffening with aging, including aortic pulse wave velocity (PWV), augmentation index (AIx), and pulse pressure (PP). The effects of aortic stiffening on peripheral vascular resistance, compliance, and function were also evaluated. We found that increased aortic stiffness occurred at middle age (>5 years old), as evidenced by an increase in PWV and AIx (p < 0.001), but with no changes in blood pressure and PP. With advancing age, increased femoral vascular resistance positively correlated with aortic PWV and AIx (p < 0.01). No significant difference in endothelium function and arterial compliance for femoral and small peripheral arteries was observed between young and middle-aged groups. The serum Klotho levels were lower in young and higher in middle-aged pigs (p < 0.001), and a positive correlation was found between Klotho and aortic PWV, AIx, and femoral vascular resistance (p < 0.01). Our findings suggest that early-aged aortic stiffening has adverse effect on peripheral hemodynamics, independent of blood pressure levels. Elevated Klotho secretion was associated with increased aortic stiffness and peripheral vascular resistance with aging.


Some lesser-known advantages of the metric system for acceleration research.
The metric system offers, due to its simplicity and uniformity, substantial advantages for the entire scientific community. To encourage those who may feel the the road to metrication is paved with agonizing frustrations, the author points out some lesser-known advantased of the metric system pertaining to acceleration research.


A functional magnetic resonance imaging study of human brain in pain-related areas induced by electrical stimulation with different intensities.
Pain-related studies have mainly been performed through traditional methods, which lack the rigorous analysis of anatomical locations. Functional magnetic resonance imaging (fMRI) is a noninvasive method detecting neural activity, and has the ability to precisely locate related activations in vivo. Moreover, few studies have used painful stimulation of changed intensity to investigate relevant functioning nuclei in the human brain. This study mainly focused on the pain-related activations induced by electrical stimulation with different intensities using fMRI. Furthermore, the electrophysiological characteristics of different pain-susceptible-neurons were analyzed to construct the pain modulatory network, which was corresponding to painful stimulus of changed intensity. Twelve volunteers underwent functional scanning receiving different electrical stimulation. The data were collected and analyzed to generate the corresponding functional activation maps and response time curves related to pain. The common activations were mainly located in several specific regions, including the secondary somatosensory cortex (SII), insula, anterior cingulate cortex (ACC), thalamus, and other cerebral regions. Moreover, innocuous electrical stimulation primarily activated the lateral portions of SII and thalamus, as well as the posterior insula, anterior ACC, whereas noxious electrical stimulation primarily activated the medial portions of SII and thalamus, as well as the anterior insula, the posterior ACC, with larger extensions and greater intensities. Several specified cerebral regions displayed different response patterns during electrical stimulation by means of fMRI, which implied that the corresponding pain-susceptible-neurons might process specific aspects of pain. Elucidation of functions on pain-related regions will help to understand the delicate pain modulation of human brain.


The Contribution of Epigenetics to Cancer Immunotherapy.
Effective anticancer immunotherapy treatments constitute a qualitative leap in cancer management. Nonetheless, not all patients benefit from such therapies because they fail to achieve complete responses, suffer frequent relapses, or develop potentially life-threatening toxicities. Epigenomic signatures in immune and cancer cells appear to be accurate and promising predictors of patient outcomes with immunotherapy. In addition, combined treatments with epigenetic drugs can exploit the dynamic nature of epigenetic changes to potentially modulate responses to immunotherapy. Candidate epigenetic biomarkers may provide a rationale for patient stratification and precision medicine, thus maximizing the chances of treatment success while minimizing unwanted effects. We present a comprehensive up-to-date view of potential epigenetic biomarkers in immunotherapy and discuss their advantages over other indicators.


Insights into earthquake hazard map performance from shaking history simulations.
Why recent large earthquakes caused shaking stronger than shown on earthquake hazard maps for common return periods is under debate. Explanations include: (1) Current probabilistic seismic hazard analysis (PSHA) is deficient. (2) PSHA is fine but some map parameters are wrong. (3) Low-probability events consistent with a map sometimes occur. This issue has two parts. Verification involves how well maps implement PSHA ("have we built the map right?"). Validation asks how well maps forecast shaking ("have we built the right map?"). We explore how well a map can ideally perform by simulating an area's shaking history and comparing "observed" shaking to that predicted by a map generated for the same parameters. The simulations yield shaking distributions whose mean is consistent with the map, but individual shaking histories show large scatter. Infrequent large earthquakes cause shaking much stronger than mapped, as observed. Hence, PSHA seems internally consistent and can be regarded as verified. Validation is harder because an earthquake history can yield shaking higher or lower than the hazard map without being inconsistent. As reality gives only one history, it is hard to assess whether misfit between a map and actual shaking reflects chance or a map biased by inappropriate parameters.


Psoriatic arthritis: what ultrasound can provide us.
Ultrasound (US) is a valuable imaging technique for detection and characterisation of the inflammatory process in arthritides. US has widely been applied to psoriatic arthritis (PsA) in both clinical and research fields, especially focusing on enthesitis. US has proven to be useful to establish a diagnosis of PsA, to recognise subclinical involvement, (such as enthesis abnormalities in patients with PsA, and in patients with only clinically apparent skin psoriasis despite the absence of clinical symptoms of arthritis), to estimate disease activity, and to allow therapy monitoring showing structural and inflammatory changes (not only in joints and tendons, but also in domains not assessed in usual rheumatology care, such as the skin and nails).


Unlocking the hidden potential of Mexican teosinte seeds: revealing plant growth-promoting bacterial and fungal biocontrol agents.
The bacterial component of plant holobiont maintains valuable interactions that contribute to plants' growth, adaptation, stress tolerance, and antagonism to some phytopathogens. Teosinte is the grass plant recognized as the progenitor of modern maize, domesticated by pre-Hispanic civilizations around 9,000 years ago. Three teosinte species are recognized: Zea diploperennis, Zea perennis, and Zea mays. In this work, the bacterial diversity of three species of Mexican teosinte seeds was explored by massive sequencing of 16S rRNA amplicons. Streptomyces, Acinetobacter, Olivibacter, Erwinia, Bacillus, Pseudomonas, Cellvibrio, Achromobacter, Devosia, Lysobacter, Sphingopyxis, Stenotrophomonas, Ochrobactrum, Delftia, Lactobacillus, among others, were the bacterial genera mainly represented. The bacterial alpha diversity in the seeds of Z. diploperennis was the highest, while the alpha diversity in Z. mays subsp. mexicana race was the lowest observed among the species and races. The Mexican teosintes analyzed had a core bacteriome of 38 bacterial genera, including several recognized plant growth promoters or fungal biocontrol agents such as Agrobacterium, Burkholderia, Erwinia, Lactobacillus, Ochrobactrum, Paenibacillus, Pseudomonas, Sphingomonas, Streptomyces, among other. Metabolic inference analysis by PICRUSt2 of bacterial genera showed several pathways related to plant growth promotion (PGP), biological control, and environmental adaptation. The implications of these findings are far-reaching, as they highlight the existence of an exceptional bacterial germplasm reservoir teeming with potential plant growth promotion bacteria (PGPB). This reserve holds the key to cultivating innovative bioinoculants and formidable fungal antagonistic strains, thereby paving the way for a more sustainable and eco-friendly approach to agriculture. Embracing these novel NGS-based techniques and understanding the profound impact of the vertical transference of microorganisms from seeds could revolutionize the future of agriculture and develop a new era of symbiotic harmony between plants and microbes.


Reciprocal Effects between Sleep Quality and Life Satisfaction in Older Adults: The Mediating Role of Health Status.
to examine the causal relationship between sleep quality and life satisfaction and explore the mediating role of health status on the relationship between sleep quality and life satisfaction. A total of 1856 older Chinese people participating in 2011, 2014, and 2018 waves of the Chinese Longitudinal Healthy Longevity Survey (CLHLS) were included. A cross-lagged panel analysis (CLPA) combined with mediator analysis was utilized. The average sleep quality levels for the years 2011, 2014, and 2018 were 3.70, 3.63, and 3.47 out of 5, respectively. The corresponding average levels of health status were 3.47, 3.44, and 3.39 out of 5, and the average levels of life satisfaction were 3.75, 3.86, and 3.87 out of 5, respectively. In addition, sleep quality at prior assessment points was significantly associated with life quality at subsequent assessments, and vice versa. Also, health status partially mediated this prospective reciprocal relationship. There is a nonlinear decreased trend in sleep quality and health status, while there exists a nonlinear increased trend in life satisfaction for older adults from 2011 to 2018. Reciprocal positive effects between sleep quality and life satisfaction in older adults exist and are mediated by health status.


Measurement of serum theophylline concentrations using a modified Ames TDA system.
Results are presented which show that the Ames TDA Theophylline kit provides an accurate and reliable method of measuring the concentration of theophylline in plasma. It may be used with a shortened incubation time (5 min) without loss of accuracy, and a single calibration curve can be used over a 3-week period. There is an acceptable precision at all assayed levels (coefficient of variation, 3.3%) and results obtained for patients' samples correlate well with those obtained using liquid chromatography (y = 0.02 + 1.06x, r = 0.99) and enzyme immunoassay (y = 0.58 + 1.03x, r = 0.99).


Fit analysis in latent trait measurement models.
The analysis of fit, whether viewed from the prospective of the fit of the data to the measurement model, or the fit of the measurement model to the data, is an important part of using latent trait models. In the case of the Rasch model, all of the desirable characteristics of the model (interval item and person measures, asymptotic standard errors, parameter invariance across subsets of persons or items, to name a few) are predicated on the requirement that the data fit the model. To the extent that the data do not fit the model, these properties hold to a lesser degree. The analysis of fit is of primary importance if the interpretation of the calibration results is to be useful. This article explores the nature of fit and provides a historical overview of fit indices. It then focuses on a particular family of fit indices that are based on the Pearsonian chi-square approach to fit, in an attempt to show why it is necessary to use a family of standardized fit indices to completely understand the relationship between the data and the model.


Dynamic structure of membranes by deuterium NMR.
Progress in our understanding of the dynamic structure of membrane lipids and proteins has recently been made possible by the advent of high-field "solid-state" nuclear magnetic resonance spectroscopic studies of specifically deuterium-labeled systems. Major features of lipid and protein dynamics have been deduced.


Chemiluminescence of carbon dots under strong alkaline solutions: a novel insight into carbon dot optical properties.
We report the surprising chemiluminescence (CL) behavior of fluorescent carbon dots in the presence of a strong alkaline solution, such as NaOH or KOH. The CL intensity was dependent on the concentration of the base and carbon dots in a certain range. A possible CL mechanism was studied by UV-Vis, fluorescence, CL, FTIR, XPS and EPR spectroscopy. Radiative recombination of the injected electrons by "chemical reduction" of carbon dots with thermally excited generated holes was proposed, which sheds new light on the characteristics of carbon dots.


Competitive endogenous RNA networks: integrated analysis of non-coding RNA and mRNA expression profiles in infantile hemangioma.
Infantile hemangioma (IH) is the most common vascular tumour in infants. The pathogenesis of IH is complex and poorly understood. Therefore, achieving a deeper understanding of IH pathogenesis is of great importance. Here, we used the Ribo-Zero RNA-Seq and HiSeq methods to examine the global expression profiles of protein-coding transcripts and non-coding RNAs, including miRNAs and lncRNAs, in IH and matched normal skin controls. Bioinformatics assessments including gene ontology (GO) and kyoto encyclopedia of genes and genomes (KEGG) pathway analyses were performed. Of the 16370 identified coding transcripts, only 144 were differentially expressed (fold change ≥ 2, P ≤ 0.05), including 84 up-regulated and 60 down-regulated transcripts in the IH samples compared with the matched normal skin controls. Gene ontology analysis of these differentially expressed transcripts revealed 60 genes involved in immune system processes, 62 genes involved in extracellular region regulation, and 35 genes involved in carbohydrate derivative binding. In addition, 256 lncRNAs and 142 miRNAs were found to be differentially expressed. Of these, 177 lncRNAs and 42 miRNAs were up-regulated in IH, whereas 79 lncRNAs and 100 miRNAs were down-regulated. By analysing the Ribo-Zero RNA-Seq data in combination with the matched miRNA profiles, we identified 1256 sponge modulators that participate in 87 miRNA-mediated, 70 lncRNA-mediated and 58 mRNA-mediated interactions. In conclusion, our study uncovered a competitive endogenous RNA (ceRNA) network that could further the understanding of the mechanisms underlying IH development and supply new targets for investigation.


Mechanistic Insights into Photocatalyzed Hydrogen Desorption from Palladium Surfaces Assisted by Localized Surface Plasmon Resonances.
Nanoparticles synthesized from plasmonic metals can absorb low-energy light, producing an oscillation/excitation of their valence electron density that can be utilized in chemical conversions. For example, heterogeneous photocatalysis can be achieved within heterometallic antenna-reactor complexes (HMARCs), by coupling a reactive center at which a chemical reaction occurs to a plasmonic nanoparticle that acts as a light-absorbing antenna. For example, HMARCs composed of aluminum antennae and palladium (Pd) reactive centers have been demonstrated recently to catalyze selective hydrogenation of acetylene to ethylene. Here, we explore within a theoretical framework the rate-limiting step of hydrogen photodesorption from a Pd surface-crucial to achieving partial rather than full hydrogenation of acetylene-to understand the mechanism behind the photodesorption process within the HMARC assembly. To properly describe electronic excited states of the metal-molecule system, we employ embedded complete active space self-consistent field and n-electron valence state perturbation theory to second order within density functional embedding theory. The results of these calculations reveal that the photodesorption mechanism does not create a frequently invoked transient negative ion species but instead enhances population of available excited-state, low-barrier pathways that exhibit negligible charge-transfer character.


Monitoring of Processing Conditions of an Ultrasonic Vibration-Assisted Ball-Burnishing Process.
Although numerous references present the beneficial effects on surface integrity of ultrasonic vibration-assisted ball burnishing (UVABB), nothing has been reported about the dynamic behavior of the UVABB tool, workpiece, and machine triad during the process. In this paper, a dynamic monitorization through a set of 5 accelerometers is tested to analyze the interactions between the tool-workpiece-machine mechanical assembly. A UVABB tool attached to a milling machine and equipped with a piezoelectric stack that is able to assist the process with a 40-kHz vibration is tested on a milled C45 steel surface. First, the natural frequencies of the mechanical system are obtained through hammer impact tests. Then, the vibratory signals transmitted during the execution of the process are monitored and compared to those: two feed velocities and two burnishing preloads, all with and without vibration-assistance. Results show that the proposed accelerometer set is valid to assess the behavior of a UVABB process. The system's natural frequencies are not varied by vibration-assistance and are not excited when the piezoelectric is functioning. It is confirmed that UVABB is safe for the machine and the tool, and there is no unexpected excited frequencies due to the piezoelectric excitation.


[THREE CASE REPORTS OF METACHRONOUS BILATERAL TESTICULAR TUMOR: INVESTIGATION OF SEXUAL FUNCTION AND FERTILITY].
The sexual dysfunction and infertility after treatment of bilateral germ cell tumors (GCT) becomes the serious problem. Therefore andrological aspects as well as cancer curability should be considered in planning of bilateral GCT treatment. Here we report 3 cases of metachronous bilateral GCT treated with different regimens, and discuss from the viewpoint of preservation of sexual function. Case presentations: (1) A 38-year-old man underwent right-sided orchitectomy for a right testicular tumor at the age of 26 years. Pathological diagnosis was seminoma and clinical stage was T1N0M0S2. 12 years later, contralateral testicular tumor developed. Left-sided orchitectomy was performed. Pathological diagnosis was seminoma and clinical stage was T1N0M0S2. He has been followed up for 4 years after the second operation without any evidence of tumor recurrence. Endocrinological examination show low testosterone level, and high LH and FSH levels. Erection and ejaculation are impossible but he does not request androgen replacement therapy. (2) A 21-year-old man underwent right-sided orchitectomy for a right testicular seminoma at the age of 20 years (T1 N0M0S0). 1 year later, contralateral seminoma (T1N0M0S0) developed and left-sided organ-preserving operation was performed. Histologic specimens showed seminoma and intratubular malignant germ cells (ITMGC) in surrounding seminiferous tubules. 2 cycles of BEP was added after the operation. He has been followed up for 5 years without any evidence of tumor recurrence. Endocrinological examination shows normal levels of testosterone and LH, but FSH is slightly high. Erection and ejaculation are possible. (3) A 36-year-old man underwent right-sided orchitectomy for a right testicular embryonal carcinoma at the age of 30 years. Clinical T1N0M0S1 was confirmed. 6 years later, he noticed the induration at his left testis. The result of fine needle aspiration cytology was embryonal carcinoma. At first, organ-preserving operation after chemotherapy was planned. However, he refused the operation considering the possibility of erectile dysfunction and infertility. As a result, he received only chemotherapy (3 cycles of BEP), and has been free of the disease for 11 years after chemotherapy. The level of testosterone, LH, and FSH are all normal. Erection and ejaculation are possible.


Dramatic Modification of Coupled-Plasmon Resonances Following Exposure to Electron Beams.
Studies of the plasmon resonances in individual and coupled metal nanoparticles often involve imaging of the nanostructures of interest in an electron microscope. We show that this process can dramatically modify the optical spectra of coupled plasmonic nanoparticles, illustrated here with the case of gold nanorod-nanosphere dimers. The spectral changes are due to the thin, partially conductive carbonaceous layer that deposits onto the particles during imaging. These changes are particularly significant for coupled nanoparticles with subnanometer interparticle gaps but have largely been neglected in previous studies of such structures, including studies intended to probe quantum-mechanical effects in plasmon coupling. Accounting for the effects of the carbonaceous layer will lead to a more accurate understanding of such systems.


Low levels of gamma-aminobutyric acid in cerebrospinal fluid of dogs with epilepsy.
gamma-Aminobutyric acid (GABA) levels were determined in cisternal cerebrospinal fluid (CSF) of 19 epileptic dogs with generalized tonic-clonic (grand mal) seizures using a radioreceptor assay. Thirty-four healthy age-matched dogs served as controls. The average CSF GABA level in epileptic dogs (40 pmol/ml) was significantly lower than that determined in controls (66 pmol/ml). Treatment with phenobarbital or primidone seemed not to affect CSF GABA levels.


Unraveling the structural basis for the unusually rich association of human leukocyte antigen DQ2.5 with class-II-associated invariant chain peptides.
Human leukocyte antigen (HLA)-DQ2.5 (DQA1*05/DQB1*02) is a class-II major histocompatibility complex protein associated with both type 1 diabetes and celiac disease. One unusual feature of DQ2.5 is its high class-II-associated invariant chain peptide (CLIP) content. Moreover, HLA-DQ2.5 preferentially binds the non-canonical CLIP2 over the canonical CLIP1. To better understand the structural basis of HLA-DQ2.5's unusual CLIP association characteristics, better insight into the HLA-DQ2.5·CLIP complex structures is required. To this end, we determined the X-ray crystal structure of the HLA-DQ2.5· CLIP1 and HLA-DQ2.5·CLIP2 complexes at 2.73 and 2.20 Å, respectively. We found that HLA-DQ2.5 has an unusually large P4 pocket and a positively charged peptide-binding groove that together promote preferential binding of CLIP2 over CLIP1. An α9-α22-α24-α31-β86-β90 hydrogen bond network located at the bottom of the peptide-binding groove, spanning from the P1 to P4 pockets, renders the residues in this region relatively immobile. This hydrogen bond network, along with a deletion mutation at α53, may lead to HLA-DM insensitivity in HLA-DQ2.5. A molecular dynamics simulation experiment reported here and recent biochemical studies by others support this hypothesis. The diminished HLA-DM sensitivity is the likely reason for the CLIP-rich phenotype of HLA-DQ2.5.


Effects of silibinin on hepatic warm ischemia-reperfusion injury in the rat model.
Liver ischemia-reperfusion injuries (I/RI) are typically the main causes of liver dysfunction after various types of liver surgery especially liver transplantation. Radical components are the major causes of such direct injuries. We aimed to determine the beneficial effects of silibinin, a potent radical scavenger on liver I/RI. Thirty-two rats were divided into 4 groups. Group I: VEHICLE, the rats underwent laparotomy and received DMSO, group II: SILI, laparotomy was done and silibinin was administered. Group III: I/R, the rats received DMSO and were subjected to a liver I/R procedure and group IV: I/R+SILI, the animals underwent the I/R procedure and received silibinin. After 1 hr of ischemia followed by 3 hr reperfusion, blood was collected to evaluate the serum marker of liver injuries. Hepatic tissue was harvested to investigate glycogen content, histological changes, and vasoregulatory gene expression. Results showed that serum AST, ALT, LDH, GGT, ALP, and hyaluronic acid (HA) increased significantly in I/R group compared with the VEHICLE group. Silibinin reduced this elevation except for GGT. Silibinin inhibited hepatocyte vacuolization and degeneration, endothelium damages, sinusoidal congestion and inflammation, and glycogen depletion during I/R. ET-1 mRNA was overproduced in the I/R group compared with the VEHICLE group which was decreased by silibinin. KLF2 and eNOS expression was reduced during I/R compared with the VEHICLE group. Silibinin elevated KLF2 expression but had no meaningful effect on eNOS expression. Silibinin protected the liver from I/RI. Silibinin could improve liver circulation by preventing sinusoidal congestion, inflammation, and perhaps modification of the vasoregulatory gene expression.


Embryological background of truncular venous malformation in the extracranial venous pathways as the cause of chronic cerebro spinal venous insufficiency.
The truncular venous malformation (VM) represents an embryologically defective vein where developmental arrest has occurred during the vascular trunk formation period in the 'later stage' of the embryonic development. A relatively simple truncular VM lesion such as a venous web at the hepatic venous outlet causes portal hypertension giving a profound damage/impact to the liver. A similar condition involving the head and neck venous system may cause chronic cerebro-spinal venous insufficiency (CCSVI) and may be involved in the development or exacerbation of multiple sclerosis.


Radio ultrasound observations of the fetotoxic effects in sheep from ingestion of Conium maculatum (poison-hemlock).
Fetal movement in pregnant ewes gavaged with Conium maculatum (poison-hemlock) was reduced significantly, but temporarily. Fetal movement was observed by radio ultrasound at 45, 54 and 60 days of gestation in control ewes and on days 45, 54, and 60 of gestation immediately before and 1 hour following poison-hemlock feeding in treated ewes. Fetal movement was significantly reduced (P less than 0.01) 1 hour after poison-hemlock administration, but returned to normal within 18 hours post treatment. At parturition seven of eleven lambs born to seven treated ewes had varying degrees of front limb abnormalities. Modest to moderate flexure of the carpal joints, some lateral deviation in the front limbs at the pastern joint and kinked tails were observed. These malformations were transient and resolved spontaneously by 8 weeks after lambing.


Personalized therapy: CNS HGNET-BCOR responsiveness to arsenic trioxide combined with radiotherapy.
High-grade neuroepithelial tumor of the central nervous system with BCOR alteration (HGNET-BCOR) is a rare, highly malignant tumor. At the time of this publication, no standard protocol exists to treat this tumor entity. In this work, we tested the responsiveness of the primary culture PhKh1 derived from tumor tissue from a pediatric HGNET-BCOR patient (P1) to inhibitors of the Sonic hedgehog pathway combined with radiation. The SMO inhibitors vismodegib and itraconazole had low effect on the proliferation of the PhKh1 cells. However, the GLI inhibitor arsenic trioxide reduced the expression of GLI target genes in the PhKh1 cells and in combination with radiotherapy significantly decreased their clonogenic potential. PhKh1 cells resistant to arsenic trioxide were characterized by the overexpression of molecular chaperones. We combined arsenic trioxide and radiation in the relapse therapy protocol of P1, achieving complete remission after seven weeks. Clinical remission lasted for six months, when P1 developed systemic metastases. Meanwhile, an increase in the concentration of circulating tumor DNA carrying a BCOR internal tandem duplication was observed. Molecular characterization of a second patient (P2) was also performed. In P2, we detected a larger tandem duplication and greater activation of the Sonic hedgehog pathway than in P1. These findings suggest that combining arsenic trioxide with radiotherapy may represent a new therapeutic approach. Moreover, peripheral blood analysis for circulating tumor DNA could help in the early detection of systemic metastases.


Prolyl Hydroxylase Domain-2 Inhibition Improves Skeletal Muscle Regeneration in a Male Murine Model of Obesity.
Obesity leads to a loss of muscle mass and impaired muscle regeneration. In obese individuals, pathologically elevated levels of prolyl hydroxylase domain enzyme 2 (PHD2) limit skeletal muscle hypoxia-inducible factor-1 alpha and vascular endothelial growth factor (VEGF) expression. Loss of local VEGF may further impair skeletal muscle regeneration. We hypothesized that PHD2 inhibition would restore vigorous muscle regeneration in a murine model of obesity. Adult (22-week-old) male mice were fed either a high-fat diet (HFD), with 60% of calories derived from fat, or a regular diet (RD), with 10% of calories derived from fat, for 16 weeks. On day 5 following cryoinjury to the tibialis anterior muscle, newly regenerated muscle fiber cross-sectional areas were significantly smaller in mice fed an HFD as compared to RD, indicating an impaired regenerative response. Cryoinjured gastrocnemius muscles of HFD mice also showed elevated PHD2 levels (twofold higher) and reduced VEGF levels (twofold lower) as compared to RD. Dimethyloxalylglycine, a cell permeable competitive inhibitor of PHD2, restored VEGF levels and significantly improved regenerating myofiber size in cryoinjured mice fed an HFD. We conclude that pathologically increased PHD2 in the obese state drives impairments in muscle regeneration, in part by blunting VEGF production. Inhibition of PHD2 over activity in the obese state normalizes VEGF levels and restores muscle regenerative potential.


Triptolide-Assisted Phosphorylation of p53 Suppresses Inflammation-Induced NF-κB Survival Pathways in Cancer Cells.
Chronic inflammation plays important roles in cancer initiation and progression. Resolving chronic inflammation or blocking inflammatory signal transduction may prevent cancer development. Here, we report that the combined low-dose use of two anti-inflammatory drugs, aspirin and triptolide, reduces spontaneous lung cancer incidence from 70% to 10% in a mouse model. Subsequent studies reveal that such treatment has little effect on resolving chronic inflammatory conditions in the lung, but it significantly blocks the NF-κB-mediated expression of proliferation and survival genes in cancer cells. Furthermore, triptolide and aspirin induce distinct mechanisms to potentiate each other to block NF-κB nuclear localization stimulated by inflammatory cytokines. While aspirin directly inhibits IκB kinases (IKKs) to phosphorylate IκBα for NF-κB activation, triptolide does not directly target IKKs or other factors that mediate IKK activation. Instead, it requires p53 to inhibit IκBα phosphorylation and degradation. Triptolide binds to and activates p38α and extracellular signal-regulated kinase 1/2 (ERK1/2), which phosphorylate and stabilize p53. Subsequently, p53 competes with IκBα for substrate binding to IKKβ and thereby blocks IκBα phosphorylation and NF-κB nuclear translocation. Inhibition of p38α and ERK1/2 or p53 mutations could abolish the inhibitory effects of triptolide on NF-κB. Our study defines a new p53-dependent mechanism for blocking NF-κB survival pathways in cancer cells.


Sofosbuvir based therapy in hepatitis C patients with and without cirrhosis: Is there difference?
To compare sustained viral response to sofosbuvir/ribavirin ±interferon therapy in patients of hepatitis C with and without liver cirrhosis. This observational study of chronic hepatitis C patients was carried out at Doctors Hospital and Medical Center (DH&MC). After diagnostic workup, Sofosbuvir/ribavirin for 24 weeks or sofosbuvir/ribavirin/pegylated interferon for 12 weeks were prescribed. Primary outcome was negative HCV RNA by PCR 12 weeks after treatment completion (SVR12). Chi square χ2 and student's t test were used to analyze data. Of 216 patients included, liver cirrhosis was present in 112 (51.9%) patients and 69(31.9%) were treatment experienced. Liver disease was decompensated in 37 (17.1%) patients. Of 206 patient who completed study protocol, 173(83.1%) achieved SVR12, 89.2% (25/28) with triple therapy and 82.2% (148/180) with sofosbuvir/ribavirin therapy. Treatment response was similar between treatment naïve 86.2% (119/138) and treatment experienced 79.4% (54/68) patents. (p value 0.19) SVR12 was inferior in cirrhosis patients 75.4% (80/106) as compared to those with no cirrhosis 93% (93/100) (p value < 0.000). It was even lesser in those with decompensated liver disease 68.8% (24/35) (p value < 0.000). Treatment outcome with sofosbuvir/ribavirin combination therapy in cirrhosis patients is suboptimal especially in those with decompensation as compared to patients without liver cirrhosis.


Characterization of antisera to paired helical filaments and tau. Implication for the extent of tau tightly bound to paired helical filaments.
The two antisera to paired helical filaments (PHF) and tau, which stained neurofibrillary tangles similarly in tissue section, were characterized. Anti-PHF reacted exclusively with the carboxyl terminal portion of tau, whereas antitau reacted with the amino terminal portion. In the blots of PHF prepared in Sarkosyl (Sarkosyl-PHF), anti-PHF stained an extensive smear from the top to the bottom of the gel, while antitau did not stain this kind of smear but labeled a small amount of intact tau that was bound to Sarkosyl-PHF. An LDS- or SDS-insoluble residue of Sarkosyl-PHF was labeled with anti-PHF, but not with antitau. Antitau-defined epitopes were susceptible to protease, whereas anti-PHF-defined epitopes were unaffected. Based on these observations, we conclude that Sarkosyl-PHF were composed largely of the carboxyl terminal region of tau and accompanied by a small amount of intact tau on their surfaces.


Vasovagal syncope misdiagnosed as epilepsy for 17 years: prime importance of clinical history.
Distinguishing epilepsy from syncope often can be challenging. We report a case of a 20-year-old patient with presumed refractory epilepsy since the age of 3 years. Although the clinical suspicion of syncope was raised at the age of 9 years, key historic features were not identified, cardiac work-up was not pursued and despite lack of electrographic evidence of epilepsy, he received anticonvulsant treatment. During his presurgical evaluation for "refractory epilepsy", one typical event was captured that was associated with asystole and normal electroencephalogram. The diagnosis of vasodepressor syncope was made and anticonvulsant medication was discontinued. With this case report, we would like to emphasize the importance of a meticulous history and the need to perform continuous video electroencephalographic with simultaneous electrocardiographic recordings in the evaluation of paroxysmal events with atypical presentation. [Published with video sequences].


[Molecular biological monitoring for Streptococcus pneumoniae isolated from patients with invasive pneumococcal infection].
Pneumococcal infection is one of the most important problems of the modern medicine. Need for organization of system of epidemiological surveillance for this infection with obligatory assessment of epidemic genovariants by molecular biological methods is evident. Assessment of pneumococci isolated from patients and carriers by using multilocus sequence typing, pulse-field electrophoresis, and restriction fragments length polymorphism analysis allowed to conclude that the latter method, which have high discriminating ability, is advantageous for these purposes.


Can Babies Remember Trauma? Symbolic Forms of Representation in Traumatized Infants.
Three important areas of current inquiry concerning early trauma-the respective roles of reality and fantasy, age-related capacity for the symbolic representation of trauma, and attachment status-are approached through clinical case reports of three children seen initially at very early ages. The findings are relevant to the issue of whether preverbal infants can experience traumatic events that later are available to interpretation. The focus is for the most part on event traumas-single harrowing, life-threatening experiences-occurring at quite early ages. Three main points are emphasized. First, toddlers and infants (including neonates) can experience intense pain and show symptoms of traumatization. They are capable of experiencing an event as harrowing and life-threatening. Second, these events are capable of being memorialized or symbolically represented, that is, stored in memory in a way that can affect later behavior and learning. Third, how that traumatization resolves itself, or fails to, can be decisively affected by the functioning of the attachment system.


Measuring storage and loss moduli using optical tweezers: broadband microrheology.
We present an experimental procedure to perform broadband microrheological measurements with optical tweezers. A generalized Langevin equation is adopted to relate the time-dependent trajectory of a particle in an imposed flow to the frequency-dependent moduli of the complex fluid. This procedure allows us to measure the material linear viscoelastic properties across the widest frequency range achievable with optical tweezers.


Breast Rash After Breast Reduction: A Case Study.
Breast reduction surgery is one of the most common procedures done by plastic surgeons. Although not detrimental to the final outcome, allergic reaction can negatively impact the postoperative course. This case presentation paints the classic picture of allergic reaction after breast surgery, likely due to skin glue. The typical signs of intense pruritus and erythematous rash surrounding incisions bilaterally are present. The patient was treated with our institutional protocol with good results. Our protocol is presented and further questions posed.


Radiation exposure in endoscopic retrograde cholangiopancreatography.
Radiation exposure was studied on the basis of x-ray screening time and spotfilms taken in 3590 patients undergoing ERCP. Factors influencing radiation exposure in diagnostic procedures were the age of the patient, target duct system and gastroenteric anastomosis, while duodenal diverticula proved to be of no significance. In endoscopic sphincterotomy average fluoroscopic time was about one minute longer. In contrast to diagnostic ERC, there was an appreciable reduction of radiation exposure in endoscopic sphincterotomy with time, reflecting the growing experience of the endoscopic team. The data presented are within the acceptable range for conventional radiological Gl-examinations.


Persistence of Dactylogyrus eucalius (Monogenea: Dactylogyridae) on the short-lived host Culaea inconstans (Pisces: Gasterosteiformes).
The monogene Dactylogyrus eucalius Mizelle and Regensberger, 1945 and its ability to maintain a population from year to year on the annual fish Culaea inconstans Kirkland was examined in a small lake in central Ontario. Fish were sampled toward the end of their annual breeding season, at a time when the host population consisted of 2 cohorts, i.e., young-of-the-year (0+) and mature adults (1+). Prevalence of infection was 94%, with a mean intensity of 8.8 +/- 9.6; neither measure varied significantly with host length or between cohorts (P > 0.05). At necropsy, parasites were characterized as juveniles that included postoncomiracidia (immature, with a ventrally directed haptor) as well as developing protandrous males (body with a near-complete haptor and with little or no pigmented vitellaria), or as adults (with testis, ovarium, darkened vitellaria, and occasionally bearing a tanned egg). The proportion of juvenile to adult parasites differed significantly between cohorts (P < 0.05), with 0+ fish infected with a mixture of juveniles and adults, whereas 1+ fish had almost exclusively adult parasites. Since adult (1+) brook stickleback typically die after spawning, the increased frequency of juvenile parasites exploiting juvenile hosts may represent an evolutionary adaptation, maximizing the chances of parasites infecting hosts that will enter winter. It is suspected that 0+ fish can be infected in the nest within 2 wk of hatching and persist by effectively infecting new host recruits when they are sympatric with their parents.


Historical estimation of exposure to 1,3-butadiene, styrene, and dimethyldithiocarbamate among synthetic rubber workers.
Quantitative estimates of exposure to 1,3-butadiene (BD), styrene (STY), and dimethyldithiocarbamate (DMDTC) were developed for a follow-up study of workers at six North American synthetic rubber plants. Procedures entailed identifying tasks and jobs involving exposure, identifying factors influencing historical changes in exposure potential, and using mathematical models to calculate job- and time-period-specific exposures. Exposure metrics included 8-hour time-weighted average (TWA) intensity, the annual number of peak exposures (BD: >100 ppm, STY: >50 ppm) and TWA intensity below and above the peak threshold. The 5th and 95th percentiles of the approximate probability distribution of each exposure estimate served as its 90% uncertainty interval. Job- and year-specific estimates were linked with subjects' work histories to obtain cumulative exposure indices. Exposure estimates varied among tasks, jobs, plants, and time periods. BD TWAs were approximately 10 ppm during the 1940s-1960s and declined during the 1970s and 1980s. STY TWAs were always <2 ppm. DMDTC exposure began in the 1950s, was high through the 1960s, and later declined. BD peak exposure accounted for a large proportion of cumulative BD exposure, whereas almost none of the STY exposure was experienced at levels >50 ppm. Exposure indices were correlated. Exposures were higher than previously estimated. Multiple correlations among DMDTC, BD, and STY exposure estimates make it difficult to estimate agent-specific effects. Limitations of the methodology include the potential inaccuracy of the estimates, the lack of adequate industrial hygiene data to validate the estimates, the additional inaccuracy of linkage with poorly specified job groups, and the potential for differential exposure misclassification because the jobs and work areas where excess leukemia mortality occurred were well-known at the time of this study. Nevertheless, the new exposure estimates were highly correlated with the old, yielding equivalent exposure ranking of workers and were comparable to limited industrial hygiene data published by NIOSH.


Relative bioavailability of coenzyme Q10 formulations in human subjects.
The relative bioavailability of typical commercially available forms of coenzyme Q10 (CoQ10) was compared with that of Q-Gel, a new solubilized form of CoQ10, in human subjects in two separate trials. In the first, standard softgel capsules containing CoQ10 suspension in oil, powder-filled hardshell capsules and powder-based tablets were tested along with Q-Gel using a daily dosage of 120 mg for three weeks. The baseline plasma CoQ10 values were all very tight (0.50-0.52 microgram/mL) and after three weeks the values were 1.37, 1.63 and 1.60 micrograms/mL for the first three products and 3.31 micrograms/mL for Q-Gel. The relative bioavailability calculated using the areas under the plasma CoQ10 curve (AUC) were (micrograms/mL x time in days) 7.16 (100%), 8.97 (125%), 9.19 (128%) and for Q-Gel 22.86 (319%). The second trial, carried out to replicate the findings in the first, employed only two groups, namely the standard softgel capsules containing the suspension and Q-Gel, and the duration was extended to four weeks. Plasma CoQ10 values were: baseline 0.40 and 0.38 and after four weeks 1.26 and 2.80; the corresponding AUCs were: 8.33 (100%) and 22.75 (273%). Thus, the data from both the trials show that Q-Gel, the new solubilized form of CoQ10, is vastly superior to typical commercially available preparations of CoQ10. This means much lower doses of Q-Gel will be required to rapidly reach and maintain adequate blood CoQ10 values than with any of the other currently available products.


Complex morphology of melt-spun nylon-6 fibres investigated by 1H double-quantum-filtered NMR spin-diffusion experiments.
The complex morphology of high-speed melt-spun nylon-6 fibres hydrated with D2O was investigated using 1H double-quantum-filtered spin-diffusion NMR experiments. The magnetisation exchange from selected crystalline domains along the fibrils and interfibrils was simulated with the help of a three-dimensional solution of a spin-diffusion equation approximated by a product of one-dimensional analytical NMR signals, which correspond to a lamellar morphology. This allows to measure the sizes of crystalline and less-mobile amorphous domains along the fibrils, as well as the diameter of the fibrils and interfibril distances. A series of nylon-6 fibres with extreme values of winding speed and draw ratio was investigated. The changes detected in the domain size along the fibrils and interfibrils show the same trend in the data obtained from wide-angle X-ray diffraction and small-angle X-ray scattering.


Tai chi and reduction of depressive symptoms for older adults: a meta-analysis of randomized trials.
The aim of the present article was to systematically review the effectiveness of tai chi for reducing depressive symptoms among older adults. Electronic databases were searched through January 2011. Reference lists of systematic reviews and identified studies from the search strategy were also screened. Randomized controlled trials of tai chi compared with waiting list controls in older adults with depressive symptoms measured by a self-report depression rating scale were included. Two authors independently identified eligible studies, extracted data and assessed the included studies for risk of bias. Estimates of depressive symptoms reduction used a random effects model, and the I(2) statistic was applied to examine heterogeneity. Four trials with a total of 253 participants met the inclusion criteria. Two studies were assessed as being of high quality; the remaining two studies were rated as moderate quality. All four studies compared tai chi with a waiting list control group. The pooled standard mean difference for these studies was -0.27 (95% CI -0.52 to -0.02, P=0.03). Tai chi appeared to have a significant impact on reducing depressive symptoms compared with the waiting list control groups. Further research is recommended with larger sample sizes, more clarity on trial design and the intervention, longer-term follow up, and concomitant economic evaluations.


Preferential photoinactivation of catalase and photoinhibition of photosystem II are common early symptoms under various osmotic and chemical stress conditions.
Activity of catalase (EC 18.104.22.168) and variable fluorescence (F) were measured in sections of rye leaves (Secale cereale L. cv. Halo) that were exposed for 24 h to moderately high irradiance under osmotic or chemical stress conditions (paraquat, DCMU, mannitol, NaCl, CdCl2 , CuSO4 , Pb(NO3 )2 , KNO2 , or K2 SO3 ). Changes of the chlorophyll content and of enzyme activities related to peroxide metabolism, such as glycolate oxidase, glutathione reductase, and peroxidase, were assayed for comparison. In the presence of the herbicides paraquat and low DCMU concentrations that exert only partial inhibition of photosynthesis, as well as after most treatments with osmotic or chemical stress factors, catalase markedly declined due to a preferential photoinactivation. At higher DCMU levels catalase did not decline. At low KNO2 concentrations catalase activity was preferentially increased. In general, photoinactivation of catalase was accompanied by a decline of the F/Fm ratio, indicating photoinhibition of photosystem II, while other parameters were much more stable. Inasmuch as both catalase and the D1 reaction center protein of photosystem II have a rapid turnover in light, their steady state levels appear to decline whenever stress effects either excessively enhance deleterious oxidative conditions and degradation (e. g. Paraquat, low DCMU), or inhibit repair synthesis. Photoinactivation of catalase and of photosystem II represent specific and widely occurring early symptoms of incipient photodamage indicating stress conditions where the repair capacity is not sufficient. During prolonged exposures, e. g. to NaCl and CuSO4 , chlorophyll was bleached in light and the rate of its photodegradation increased in proportion as the catalase level had declined. The results suggest that the enhanced susceptibility of leaf tissues to photooxidative damage which is widely observed in stressed plants is related to the early loss of catalase.


Prediction of unstable anticoagulation with acenocoumarol versus warfarin in atrial fibrillation.
The SAMe-TT2R2 (sex female, age, medical history, treatment, tobacco use, race) score was developed in patients with atrial fibrillation (AF) on warfarin. The present study aimed to 1) compare the anticoagulation quality and management of AF patients treated with warfarin with those on acenocoumarol and 2) optimize the SAMe-TT2R2 score to detect AF patients at high risk of unstable anticoagulation with acenocoumarol and warfarin. In a single-center retrospective study, 320 patients with AF, including 15 (5%) after valve replacement, aged 40-82 (median 70) years, including 203 (63%) receiving acenocoumarol and 117 (37%) treated with warfarin, were studied. The SAMe-TT2R2 score was modified based on the candidate factors retrieved from univariate regression and assessed using the receiver operating curves (ROC). A median SAMe-TT2R2 score was 2 (1-3). Proportions of patients with ≥ 2 points and 0-1 points in the SAMe-TT2R2 score who had the time in therapeutic range (TTR) ≤ 70% were similar (61 [67%] vs. 63 [56%], p = 0.11). A modified score, involving medical history (myocardial infarction [MI] and chronic obstructive pulmonary disease [COPD], 1 point), statin treatment (1 point) and tobacco use (2 points) had a higher area under the curve (AUC) in patients on acenocoumarol compared to SAMe- TT2R2 (0.66; 95% confidence interval 0.58-0.73 vs. 0.56; 0.48-0.64, p = 0.042); ≥ 1 point indicated TTR > 70% with a sensitivity and specificity of 61% and 63%, respectively. The SAMe-TT2R2 score is less effective in predicting unstable anticoagulation with acenocoumarol versus warfarin. Adding statin use and highlighting COPD and previous MI increases a predictive value of this score for acenocoumarol.


Discount functions and the measurement of patients' values. Women's decisions during childbirth.
This paper discusses the measurement of patients' values for future outcomes and examines some problems clinicians confront when making management decisions that attempt to comply with those values. It presents a model that implies that a patient's preference varies with the passage of time, and that during certain periods of time a patient's values may not be representative of his or her long-term preference. An examination of the attitudes of 18 pregnant women toward avoiding pain and avoiding anesthesia bore out the predictions of this model. The women preferred to avoid using anesthesia during childbirth when asked one month before labor and during early labor; however, during active labor their preferences suddenly shifted toward avoiding pain (p less than 0.05). Their preference shifted again toward avoiding the use of anesthesia (p less than 0.05) when evaluated at one month postpartum. The women's preferences one month before labor were the best predictors of their postpartum preferences. The women's preferences during active labor and transition phase of labor were unrelated to their postpartum preferences. These results suggest that, depending upon when a patient's values are measured, (1) they may not be representative of his or her long-term preference, and (2) their use in decision analyses may not maximize the patient's long-term satisfaction so much as they maximize the probability that the decision will be based on the patient's impulsive response. These results also imply that (3) patients may make inherently less reliable value assessments of abstract outcomes they have never experienced, and (4) the distinction between current and long-term values can create a problem when determining whether people behave rationally.


High faecal calprotectin levels in intestinal tuberculosis are associated with granulomas in intestinal biopsies.
The diagnosis of intestinal tuberculosis (ITB) is sometimes difficult to establish and requires endoscopic investigation with biopsies for histopathological examination. This study aimed to evaluate calprotectin as a marker of inflammation in ITB. Patients with ITB were prospectively recruited in Southern India from October 2009 until July 2012. Demographic, clinical, endoscopic and histological features were examined along with faecal calprotectin (FC), serum calprotectin (SC) and C-reactive protein (CRP). Thirty patients (median age 34.5 years, 19 men) were included. Clinical features were abdominal pain (97%), weight loss (83%), cachexia (75%), fatigue (63%), watery diarrhoea (62%), nausea (55%) and fever (53%). Endoscopy showed transverse ulcers (61%), nodularity of mucosa (55%), aphthous ulcers (39%), strictures (10%) and fissures (10%). The terminal ileum and right colon harboured 81% of the lesions. Histology revealed granulomas in biopsies from 10 of the patients. FC and CRP levels showed a strong positive correlation (rs = 0.70, p < 0.01). FC, SC and CRP levels were higher in the granulomatous than the non-granulomatous patients, respectively (median FC 988 μg/g, interquartile range (IQR) 940 vs 87 μg/g, IQR 704, p < 0.01; median SC 8.2 μg/ml, IQR 7.3 vs 3.8 μg/ml, IQR 8.9, p = 0.23; median CRP 38.8 mg/L, IQR 42.9 vs 2.3 mg/L, IQR 13.5, p < 0.01). Higher median calprotectin and CRP levels were detected in patients with extensive than localized disease, but the differences did not reach statistical significance. ITB patients with granulomas on histology have high levels of faecal calprotectin and CRP.


Lysosomal enzyme release from macrophages: a model of food yeast toxicity evaluation.
The role of lysosomal enzyme released by macrophages was examined in relation to the toxic effect caused by food yeast. Mouse peritoneal macrophages exposed to yeast in culture showed marked release of N-acetyl glucosaminidase, beta-galactosaminidase and beta-glucuronidase below the median lethal dose (LD50). LD50 was measured from the dose response curves of the cytoplasmic lactate dehydrogenase enzyme. Saccharomyces cerevisiae showed the highest LD50 followed by Kluyveromyces fragilis and Candida utilis yeast. LD50 values obtained as well as the in vitro lysosomal release by mouse peritoneal macrophages may be relevant to assess the toxic capacity of food yeast intended for human consumption.


Maxillary Sinus Augmentation Using a Titanium Mesh: A Randomized Clinical Trial.
Various attempts have been implemented using different materials and techniques to augment the maxillary sinus floor for prospect dental implant positioning. This contemplate was conducted to assess the osteogenic capability of the maxillary sinus in a two-step sinus membrane elevation using titanium mesh to keep the formed space to place dental implants in atrophic ridges. Titanium micromesh was customized and positioned into the sinus on one side to preserve the elevated membrane in position. On the other side xenograft was applied. Instant and 6-months postoperative cone beam computed tomography (CBCT) was done to assess the gained bone height and density. Bone core biopsies were obtained during implant placement for histological and histomorphometric evaluation. The average bone height values increased in both groups. Meanwhile the average bone density value was higher at the graft group than the titanium mesh group. Histological and histomorphometric evaluation presented the average bone volume of the newly formed bone in the graft group which is superior to that of the titanium mesh group. The use of the titanium micromesh as a space-maintaining device after Schneiderian membrane elevation is a trustworthy technique to elevate the floor of the sinus without grafting.


Retrospective analyses of routine preoperative blood testing in a tertiary eye hospital: could Choosing Wisely work in China?
To explore the possibility of implementing Choosing Wisely on ocular patients in China by investigating the prevalence of abnormalities in routine preoperative blood tests (RPBTs) and its turnaround time (TAT). Data from 102 542 ocular patients between January 2016 and December 2018, at Zhongshan Ophthalmic Center, were pooled from the laboratory information system. The test results were divided into normal and abnormal, including critical values. Ocular diseases were stratified into 11 subtypes based on the primary diagnosis. The TAT of 243 350 blood tests from January 2017 to December 2018 was categorised into transportation time and intralaboratory time. RPBT was grouped into complete blood count (CBC), blood biochemistry (BBC), blood coagulation (BCG) and blood-borne pathogens (BBP), completed for 97.22%, 87.66%, 94.41% and 95.35% of the recruited patients (male, 52 549 (51.25%); median(IQR) age, 54 (29-67) years), respectively. Stratified by the test items, 9.19% (95% CI 9.07% to 9.31%) were abnormal results, and 0.020% (95% CI 0.019% to 0.022%) were critical; most abnormalities were on the CBC, while glucose was the most common critical item. Classified by the patients' primary diagnosis, 76.97% (95% CI 76.71% to 77.23%) had at least one abnormal result, and 0.28% (95% CI 0.25% to 0.32%) were critical; abnormal findings were reported in 45.29% (95% CI 44.98% to 45.60%), 54.97% (95% CI 54.65% to 55.30%), 30.29% (95% CI 30.00% to 30.58%) and 11.32% (95% CI 11.12% to 11.52%) for the CBC, BBC, BCG and BBP tests, respectively. The median transportation time and intralaboratory TAT of the samples were 12 min and 78 min respectively. Blood abnormalities are common in ocular patients. With acceptable timelines, RPBT is still indispensable in China for patient safety.


Safety evaluation of an alpha-cyclodextrin glycosyltranferase preparation.
Alpha-cyclodextrin glucosyltransferase (alpha-CGTase, EC 22.214.171.124) is an amylolytic enzyme used for the production of alpha-cyclodextrin (alpha-CD), a novel, soluble dietary fiber, from food-grade starch. The safety of an alpha-CGTase preparation obtained by batch fermentation from a recombinant strain of Escherichia coli K12 harboring the alpha-CGTase gene from Klebsiella oxytoca strain M5a1 was examined. In a 13-week subchronic toxicity study in rats, the administration by gavage of the alpha-CGTase preparation at levels of up to 20 ml/kg bw/day, corresponding to a total organic solids dosage of 260 mg/kg bw/day, did not cause any systemic toxic effect. Some signs of irritation were observed in the respiratory tract which occurred, however, in one sex only and/or were not dose-related. Accordingly, these changes were considered to be an unspecific consequence of the reflux and aspiration of the dosing solution. There was no evidence of a genotoxic activity in Ames tests and a chromosome aberration test in cultured human lymphocytes. It is concluded that the examined alpha-CGTase preparation is safe when used for the production of alpha-CD.


Altered fatty acid metabolism in long duration road transport: An NMR-based metabonomics study in sheep.
The physical, endocrine, and metabolic responses of livestock to road transport have been evaluated by conventional hematological and biochemistry parameters for more than 20 years. However, these measures are relatively insensitive to subtle metabolic adaptations. We applied NMR-based metabonomics to assess system-wide metabolic responses as expressed in urine and serum of a large cohort of animals (n = 80) subjected to 12 and 48 h road transport. The profiling of (1)H NMR spectra revealed that the transported animals experienced altered gut and energy metabolism, muscle catabolism, and possibly a renal response. The animals transported for 48 h exhibited a deeper metabolic response to the transport event and a complex and expanded metabolic trajectory over the 72 h recovery period. Intriguingly, excretion of acyl glycines and a dicarboxylic acid was observed after transport and during recovery, implicating peroxisomal fatty acid oxidation as a metabolic response to transport-induced stress.


SPECIES RICHNESS WITHIN FAMILIES OF FLOWERING PLANTS.
Variation in species and genus richness among families of flowering plants was examined with respect to four classification variables: geographical distribution, growth form, pollination mode, and dispersal mode. Previous studies have estimated rates of species proliferation from age and contemporary diversity. Here we found that the earliest appearances in the fossil record are correlated with contemporary familial species richness, abundance in the fossil record, and the independent variables considered in this analysis. Thus, we believe that the fossil record does not provide reasonable estimates of the ages of families and that the rate of species proliferation cannot be calculated from such data without bias. Accordingly, our subsequent analyses were based on contemporary species richness of families. Although the classification variables were interrelated, each made largely independent contributions to familial species richness. Cosmopolitan families were 5.6 times more species-rich than strictly tropical families and 35 times more species-rich than strictly temperate families. Families including both herbaceous and woody growth forms were 5.7 and 14 times more species-rich than families with either growth form alone. Although animal pollination was significantly associated with elevated familial species richness, the effect was statistically weak. The most prominent effect was that families with both abiotic and biotic dispersal had more than 10 times as many species as families with either dispersal mode alone. Our analyses also revealed that families having both dispersal modes were more likely to have several growth forms, suggesting that evolutionary flexibility of morphology may be generalized over diverse aspects of life history. These results do not support the idea that pollination and dispersal by animals were primarily responsible for the tremendous proliferation of angiosperm species, either by producing population structures conducive to speciation or by applying selection for diversification. Instead, the importance of varied dispersal mode, growth form, and climate zone in predicting high familial species richness suggests that a capacity to diversify morphologically and physiologically may have been primarily responsible for high rates of species proliferation in the flowering plants.


Picosecond melting of peptide nanotubes using an infrared laser: a nonequilibrium simulation study.
Self-assembled functional peptide biomaterials are emerging with a wide range of envisioned applications in the field of nanotechnology. Currently, methods and tools have been developed to control and manipulate as well as to explore new properties of self-assembled structures. However, considerably fewer studies are being devoted to developing efficient methods to degrade or recycle such extremely stable biomaterials. With this in mind, here we suggest a theoretical framework, inspired by the recent developed mid-infrared free-electron laser pulse technology, to dissociate peptide nanotubes. Adopting a diphenylalanine channel as a prototypical example, we find that the primary step in the dissociation process occurs due to the strong resonance between the carboxylate bond vibrations of the diphenylalanine peptides and the tuned laser frequencies. The effects of laser irradiation are determined by a balance between tube formation and dissociation. Our work shows a proof of concept and should provide a motivation for future experimental developments with the final aim to open a new and efficient way to cleave or to recycle bio-inspired materials.