[The effect long-term administration of a selective beta1 blocker bisoprolol on glucose metabolism in patients with essential hypertensive and type 2 diabetes mellitus].
To investigate the effects of bisoprolol on glucose metabolism and blood pressure in essential hypertensive patients with type 2 diabetes mellitus. A total of 92 hypertensive patients with type 2 diabetes on stable antidiabetic therapy with HbAlc less than 7% were recruited. In a randomized, open trial the patients were treated for 12 weeks with bisoprolol or captopril following a 1-week placebo run-in period, the main parameters measured were HbA1c, fasting blood glucose and 2-hour postprandial glucose following a standard dinner as well as systolic and diastolic blood pressure. There were no differences in HbA1 [(6.0 +/- 0.8)% vs (6.2 +/- 0.8)%, P > 0.05], fasting glucose [(7.0 +/- 1.8) mmol/L vs (7.0 +/- 1.9) mmol/L, P > 0.05], 2-hour postprandial blood glucose [(10.7 +/- 2.5) mmol/L vs (11.2 +/- 3.4) mmol/L, P > 0.05], systolic blood pressure [(147.3 +/- 9.7) mm Hg (1 mm Hg = 0.133 kPa) vs (146.2 +/- 8.3) mm Hg, P > 0.05] and diastolic blood pressure (88.3 +/- 8.9 mm Hg vs 87.8 +/- 7.9 mm Hg, P > 0.05) between the bisoprolol and captopril group before treatment. After administration of bisoprolol or captopril, there were still no differences between these two groups in HbA1c [(5.7 +/- 0.9)% vs (5.7 +/- 1.1)%, P > 0.05], fasting blood glucose [(6.8 +/- 1.6) mmol/L vs (6.4 +/- 2.1) mmol/L, P > 0.05], 2-hour postprandial glucose [(10.0 +/- 2.9) mmol/L vs (10.2 +/- +/- 2.9)mmol/L, P > 0.05], systolic blood pressure [(124.8 +/- 10.6) mm Hg vs (126.6 +/- 7.8) mm Hg, P > 0.05] and diastolic blood pressure [(74.5 +/- 7.7) mm Hg vs (77.6 +/- 7.6) mm Hg, P = 0.05]. Based on these results, bisoprolol appears to be a beta1-selective blocker possessing a satisfactory antihypertensive effect without any adverse effects on glucose metabolism and is therefore a choice for treating hypertensive patients with type 2 diabetes mellitus.


Glycan Microarrays Containing Synthetic Streptococcus pneumoniae CPS Fragments and Their Application to Vaccine Development.
Streptococcus pneumoniae is the leading source of life-endangering diseases like pneumonia, septicemia, and meningitis, as well as a major cause of death in children under 5 years old in developing countries. At least 98 serotypes of S. pneumoniae can be distinguished based on their structurally distinct capsular polysaccharides (CPS). Currently available CPS-based pneumococcal vaccines contain serotypes most frequently associated with invasive pneumococcal diseases. The polysaccharides used in commercial conjugate-vaccines are isolated from bacteria cultures comprising many laborious and operationally challenging steps followed by depolymerization of long polysaccharides into small fragments and their conjugation to the carrier protein. The medicinal chemistry approach for glycoconjugate vaccine development offers an exciting alternative to CPS isolation for a broad range of different glycan antigens. Glycan arrays containing well-defined synthetic glycans of CPS fragments and repeating units are used as a platform for the high-throughput screening of various serum samples and identification of protective glycotopes for vaccine candidates.


Combined removal of sulfur compounds and nitrate by autotrophic denitrification in bioaugmented activated sludge system.
An autotrophic denitrification process using reduced sulfur compounds (thiosulfate and sulfide) as electron donor in an activated sludge system is proposed as an efficient and cost effective alternative to conventional heterotrophic denitrification for inorganic (or with low C/N ratio) wastewaters and for simultaneous removal of sulfide or thiosulfate and nitrate. A suspended culture of sulfur-utilizing denitrifying bacteria was fast and efficiently established by bio-augmentation of activated sludge with Thiobacillus denitrificans. The stoichiometry of the process and the key factors, i.e. N/S ratio, that enable combined sulfide and nitrogen removal, were determined. An optimum N/S ratio of 1 (100% nitrate removal without nitrite formation and low thiosulfate concentrations in the effluent) has been obtained during reactor operation with thiosulfate at a nitrate loading rate (NLR) of 17.18 mmol N L(-1) d(-1). Complete nitrate and sulfide removal was achieved during reactor operation with sulfide at a NLR of 7.96 mmol N L(-1) d(-1) and at N/S ratio between 0.8 and 0.9, with oxidation of sulfide to sulfate. Complete nitrate removal while working at nitrate limiting conditions could be achieved by sulfide oxidation with low amounts of oxygen present in the influent, which kept the sulfide concentration below inhibitory levels.


WingMesh: A Matlab-Based Application for Finite Element Modeling of Insect Wings.
The finite element (FE) method is one of the most widely used numerical techniques for the simulation of the mechanical behavior of engineering and biological objects. Although very efficient, the use of the FE method relies on the development of accurate models of the objects under consideration. The development of detailed FE models of often complex-shaped objects, however, can be a time-consuming and error-prone procedure in practice. Hence, many researchers aim to reach a compromise between the simplicity and accuracy of their developed models. In this study, we adapted Distmesh2D, a popular meshing tool, to develop a powerful application for the modeling of geometrically complex objects, such as insect wings. The use of the burning algorithm (BA) in digital image processing (DIP) enabled our method to automatically detect an arbitrary domain and its subdomains in a given image. This algorithm, in combination with the mesh generator Distmesh2D, was used to develop detailed FE models of both planar and out-of-plane (i.e., three-dimensionally corrugated) domains containing discontinuities and consisting of numerous subdomains. To easily implement the method, we developed an application using the Matlab App Designer. This application, called WingMesh, was particularly designed and applied for rapid numerical modeling of complicated insect wings but is also applicable for modeling purposes in the earth, engineering, mathematical, and physical sciences.


Blood L-Lactate Concentration as an Indicator of Outcome in Roe Deer (Capreolus capreolus) Admitted to a Wildlife Rescue Center.
Roe deer (Capreolus capreolus) are among the most frequent patients of rescue centers in Italy. Three outcomes are possible: natural death, euthanasia, or treatment and release. The aim of the present study is to propose blood L-lactate concentration as a possible prognostic biomarker that may assist veterinarians in the decision-making process. Sixty-three roe deer, admitted to one rescue center in the period between July 2018 and July 2019, were sampled and divided into 4 groups according to their outcome: (1) spontaneous death (17 cases), (2) humanely euthanized (13 cases), (3) fully recovered and released (13 cases), and (4) euthanized being unsuitable for release (20 cases). In addition, blood samples from 14 hunted roe deer were analyzed as controls. Whole blood lactate concentrations were measured with a point of care lactate meter. Differences among groups were close to statistical significance (p = 0.51). A cut-off value of 10.2 mmol/L was identified: all the animals with higher values died or were humanely euthanized. The results suggest that roe deer with lactatemia higher than 10.2 mmol/L at admission, have a reduced prognosis for survival during the rehabilitation period, regardless of the reason for hospitalization and the injuries reported. Therefore, humane euthanasia should be considered for these animals.


Effect of target content at higher spatial frequencies on the accuracy of the accommodation response.
The accommodation responses to sinusoidal and square-wave gratings at the same vergence (-5.0 dioptres) are compared as a function of the modulation of the fundamental of both waveforms. At low spatial frequencies (less than or equal to 2 c deg-1), responses to square-wave gratings are found to be more accurate than those to sine-waves. At higher frequencies the responses become very similar. An explanation is offered in terms of the contribution of higher harmonics to the square-wave response.


Use of CMAP, MScan fit-MUNE, and MUNIX in understanding neurodegeneration pattern of ALS and detection of early motor neuron loss in daily practice.
The pattern of lower motor neuron (LMN) degeneration in amyotrophic lateral sclerosis (ALS), i.e., dying-back (from the nerve ending to cell body) or dying-forward (from the cell body to nerve ending), has been widely discussed. In this study, we aimed to evaluate LMN loss using compound muscle action potential (CMAP), motor unit number index (MUNIX), and MScan-fit-based motor unit number estimation (MUNE) to understand the pattern of neurodegeneration in ALS. Twenty-five patients were compared with 25 controls using CMAP amplitude and area, MUNIX, and MScan-fit MUNE in three proximal and distal muscles innervated by the ulnar nerve. Unlike the controls, the CMAP area, MScan-fit MUNE, and MUNIX recorded in ALS patients showed more neurodegeneration in distal muscles than proximal muscles. In ALS patients with unaffected CMAP amplitudes (n = 13), the CMAP area, MScan-fit MUNE, and MUNIX showed subtle motor unit loss of 30.7 %, 53.8 %, and 38.4 %, respectively. The CMAP area, MScan-fit MUNE, and MUNIX showed neurodegeneration earlier than the reduction in CMAP amplitude. These tests confirmed dying-back neurodegeneration, while only MUSIX showed re-innervation in ALS.


Differential role of the transcription factor NF-kappaB in selection and survival of CD4+ and CD8+ thymocytes.
Inhibition of the transcription factor nuclear factor (NF)-kappaB activity leads to a reduction in numbers of CD8(+) single-positive (SP) thymocytes, suggesting a selective role for NF-kappaB in these cells. To further explore the role of NF-kappaB in SP thymocytes, we utilized transgenic models that allowed either inhibition or activation of NF-kappaB. We showed that activation of NF-kappaB played an important role in the selection of major histocompatibility complex (MHC) class I-restricted CD8(+) T cells. Surprisingly, NF-kappaB was not activated in positively selected CD4(+) thymocytes, and inhibition of NF-kappaB did not perturb positive or negative selection of CD4(+) cells. However, enforced activation of NF-kappaB via a constitutively active inhibitor of kappaB (IkappaB) kinase transgene led to a nearly complete deletion of CD4 cells by pushing positively selecting CD4(+) cells into negative selection. These studies therefore revealed a surprising difference of NF-kappaB activation in CD4(+) and CD8(+) thymocytes and suggested that NF-kappaB contributes to the establishment of thresholds of signaling that determine positive or negative selection of thymocytes.


Hematopoietic cell transplant outcomes after myeloablative conditioning with fludarabine, busulfan, low-dose total body irradiation, and rabbit antithymocyte globulin.
Optimal conditioning and graft-vs-host disease (GVHD) prophylaxis for hematopoietic cell transplantation (HCT) are unknown. Here, we report on outcomes after low toxicity, myeloablative conditioning consisting of fludarabine, busulfan, and 4 Gy total body irradiation, in combination with thymoglobulin and post-transplant methotrexate and cyclosporine. We retrospectively studied 700 patients with hematologic malignancies who received blood stem cells from 7 to 8/8 HLA-matched unrelated or related donors. Median follow-up of surviving patients was 5 years. At 5 years, overall survival (OS), relapse-free survival (RFS), and chronic GVHD/relapse-free survival (cGRFS) were 58%, 55%, and 40%. Risk factors for poor OS, RFS, and cGRFS were (1). high to very high disease risk index (DRI), (2). high recipient age, and (3). cytomegalovirus (CMV)-seropositive recipient with seronegative donor (D-R+). The latter risk factor applied particularly to patients with lymphoid malignancies. Neither donor other than HLA-matched sibling (7-8/8 unrelated) nor one HLA allele mismatch was risk factors for poor OS, RFS, or cGRFS. In conclusion, the above regimen results in excellent long-term outcomes. The outcomes are negatively impacted by older age, high or very high DRI, and CMV D-R+ serostatus, but not by donor unrelatedness or one HLA allele mismatch.


The effect of sampling technique on acid-base balance and other blood parameters in the sheep.
The effect of 4 sampling routines--venipuncture, intravenous cannula, intravenous cannula following the administration of a tranquiliser (xylidino dihydrothiazine hydrochloride), intravenous cannula following exercise--were compared. Blood pH and base excess values were similar after venipuncture and cannula sampling, but higher (P less than 0 with 05) after the administration of the tranquiliser and lower (P less than 3 with 05) following exercise. Blood haemoglobin, haematocrit and lactate levels followed this pattern, while plasma protein levels were similar for all treatments except after exercise, where they were higher (P less than 0 with 05). The recovery of various blood parameters to normal values after a period of exercise was also studied: acid-base balance had returned to near normal within 60 min, while haemoglobin and haematocrit levels had returned to normal within 10 min.


Effect of long-term glycemic variability on estimated glomerular filtration rate decline among patients with type 2 diabetes mellitus: Insights from the Diabetic Nephropathy Cohort in Singapore.
In the present study, we examined the association between HbA1c variability and renal disease progression based on estimated glomerular filtration rate (eGFR) decline in patients with type 2 diabetes mellitus (T2DM) in Singapore. Glycemic burden and renal function were retrospectively assessed in 1628 patients in 2002-2014. Multivariable logistic regression was used to assess the relationships between HbA1c variability (expressed as HbA1c coefficient of variation [HbA1c-CV] in quartiles), HbA1c intrapersonal mean (HbA1c-IM), and eGFR decline, adjusted for baseline covariates. Among patients with relatively good glycemic control (i.e. HbA1c-IM below the median cohort value [8.0%]), HbA1c-CV Quartile 4 was associated with eGFR decline (odds ratio [OR] 1.88; 95% confidence interval [CI] 1.10-3.25). The OR for HbA1c-CV Quartile 4 was 2.20 (95% CI 1.24-3.89) after additional adjustment for HbA1c-IM. Where HbA1c-IM was above the median cohort value, HbA1c-CV Quartiles 3 and 4 were associated with eGFR decline, with ORs of 2.60 (95% CI 1.48-4.55) and 3.29 (95% CI 1.89-5.76) respectively. After further adjusting for HbA1c-IM, the ORs for Quartiles 3 and 4 were 2.69 (95% CI 1.53-4.74) and 3.51 (95% CI 1.98-6.21), respectively. Variability in HbA1c is strongly and independently associated with eGFR decline in patients with T2DM independent of mean HbA1c. The findings may highlight the importance of sustained stable glycemic control in management of diabetes mellitus.


The neural mechanisms of perceptual filling-in.
Filling-in is a perceptual phenomenon in which a visual attribute such as colour, brightness, texture or motion is perceived in a region of the visual field even though such an attribute exists only in the surround. Filling-in dramatically reveals the dissociation between the retinal input and the percept, and raises fundamental questions about how these two relate to each other. Filling-in is observed in various situations, and is an essential part of our normal surface perception. Here, I review recent experiments examining brain activities associated with filling-in, and discuss possible neural mechanisms underlying this remarkable perceptual phenomenon. The evidence shows that neuronal activities in early visual cortical areas are involved in filling-in, providing new insights into visual cortical functions.


Identification of an allelic variant of isoform MLC1-V/sB (human myosin light chain).
A study of 250 specimens of human myocardium by two-dimensional gel electrophoresis revealed an allelic variant of isoform MLC1-V/sB, which was identified by immunoblotting with monoclonal antibody against MLC1-V/sB and peptide mapping after in situ tryptic digestion of electroblotted proteins. The substitution Asn-144 for His-144 was found in this new allelic variant of MLC1-V/sB.


Small RNAs, RNAi and the inheritance of gene silencing in Caenorhabditis elegans.
Invasive nucleic acids such as transposons and viruses usually exhibit aberrant characteristics, e.g., unpaired DNA or abnormal double-stranded RNA. Organisms employ a variety of strategies to defend themselves by distinguishing self and nonself substances and disabling these invasive nucleic acids. Furthermore, they have developed ways to remember this exposure to invaders and transmit the experience to their descendants. The mechanism underlying this inheritance has remained elusive. Recent research has shed light on the initiation and maintenance of RNA-mediated inherited gene silencing. Small regulatory RNAs play a variety of crucial roles in organisms, including gene regulation, developmental timing, antiviral defense, and genome integrity, via a process termed as RNA interference (RNAi). Recent research has revealed that small RNAs and the RNAi machinery are engaged in establishing and promoting transgenerational gene silencing. Small RNAs direct the RNAi and chromatin modification machinery to the cognate nucleic acids to regulate gene expression and epigenetic alterations. Notably, these acquired small RNAs and epigenetic changes persist and are transmitted from parents to offspring for multiple generations. Thus, RNAi is a vital determinant of the inheritance of gene silencing and acts as a driving force of evolution.


An oncolytic conditionally replicating adenovirus for hormone-dependent and hormone-independent prostate cancer.
The use of conditionally replicating adenoviruses offers an attractive complementary treatment strategy for localized prostate cancer. We have produced a replicating adenovirus, Ad[I/PPT-E1A], where E1A gene expression is controlled by a recombinant regulatory sequence designated PPT. The PPT sequence comprises a PSA enhancer, a PSMA enhancer and a T-cell receptor gamma-chain alternate reading frame protein promoter, and it is shielded from transcriptional interference from adenoviral backbone sequences by an H19 insulator. Ad[I/PPT-E1A] yields prostate-specific E1A protein expression, viral replication and cytolysis in vitro. Furthermore, Ad[I/PPT-E1A] considerably regresses the growth of subcutaneous LNCaP prostate cancer tumors in nude mice. Importantly, the viral replication and cytolytic effect of Ad[I/PPT-E1A] are independent of the testosterone levels in the prostate cancer cells. This may be beneficial in a clinical setting since many prostate cancer patients are treated with androgen withdrawal. In conclusion, Ad[I/PPT-E1A] may prove to be useful in the treatment of localized prostate cancer.


Personalized Management of Type 2 Diabetes.
Our goal is to discuss how to personalize the management of patients with type 2 diabetes by adjusting glycemic targets and tailoring medical therapy to account for unique patient characteristics. We review the pharmacotherapeutic options for the management of type 2 diabetes, focusing on potential advantages and disadvantages of each class of agents. We also discuss how to approach specific patient subpopulations and propose a conceptual framework for incorporating these factors into clinical practice. As the diabetes treatment landscape rapidly expands, physicians have the exciting opportunity to offer patients increasingly individualized care.


A simplified filter paper assay method of cellulase enzymes based on HPLC analysis.
A simplified filter paper assay (FPA) method of cellulase enzymes was proposed based on high-performance liquid chromatography (HPLC) measurement. The method was according to the sum of glucose and cellobiose concentrations measured by HPLC that was able to be correlated with filter paper units (FPU) of the cellulase enzymes assayed by the traditional FPA method, regardless of the differences in the sources, activities, and components of the cellulases. This simple and quick assay method for the cellulase enzymes provided another parameter of the ratio of glucose to cellobiose (G/C ratio) representing the capacity of cellulase enzymes degrading cellulose into fermentable monomeric sugars.


[Psoriasis, metabolic syndrome and its components].
The psoriasis is a chronic dermatosis which is characterized by strong inflammation. Recent studies showed that the chronic inflammation plays an important part in the pathogenesis of many metabolic and vascular diseases. Moreover, the diseases mediated by lymphocytes TH1 were related to the myocardial infarction. Epidemiologic investigations showed that psoriasis is associated at the increased risk of Comorbidities and mortality per comparison to the general population. Thus, the psoriatic patients have a high prevalence of metabolic pathologies such as the diabetes, hypertension, obesity and hyperlipidemy. These concomitant affections can complicate the treatment of psoriasis. It is important that the dermatologist systematically seeks these concomitant pathologies among psoriatic patients. These data also suggest that the treatments of these patients improve not only the skin lesions, but also control the inflammation associated with the psoriasis.


Inactivation of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine by a plasma acetylhydrolase: higher activities in hypertensive rats.
We have partially characterized the properties of a specific acetylhydrolase in plasma from spontaneous hypertensive rats. This enzyme inactivates 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (a lipid involved in platelet aggregating, hypotensive, and allergic responses) by removal of the acetate group. The extent of acetate hydrolysis was linear with both time and protein concentration, and the enzyme had an apparent Km of 2.5 microM and a Vmax of 2.6 nmol/min/mg protein. As with an intracellular acetylhydrolase previously characterized by us, the plasma activity was not affected by addition of phosphatidylcholine, EDTA, or Ca2+. However, in contrast to the acetylhydrolase activity in the rat kidney soluble fraction, the plasma activity was associated with a higher molecular weight protein resolved on a Sepharose 6B column and the plasma acetylhydrolase was not inhibited by treatment with trypsin, pronase, or subtilisin. We also compared the acetylhydrolase activity in plasma of age-matched spontaneous hypertensive rats and their normotensive controls, and found approximately 20% higher levels of activity in plasma from the hypertensive animals (P less than 0.01).


Morphology and head morphometric characters of sperm in Thai native crossbred stallions.
One of the semen quality parameters use to determine fertility is the percentage of sperm that express normal morphology. Sperm head morphometry is also correlated with fertility. The objectives of this study were 1) to investigate the sperm morphology and normal sperm head morphometry of Thai native crossbred stallions, and 2) to compare our results with the characteristics of proven fertile sperm from purebred stallions. Semen samples were collected monthly from nine stallions, of which five were Thai native crossbred (T) and four were purebred of proven fertility (F: F1 was a Standard-bred; F2 was a Warm-blood; F3 and F4 were Thoroughbreds). All the animals were aged between 5 and 12 years. Sperm morphological examination was performed using formaldehyde-fixed samples under phase-contrast microscopy (1000x). Normal sperm head morphometry characteristics were measured by Computer-Assisted Semen Analysis (Hamilton Thorne, USA.) after applying the Harris' haematoxylin staining technique. The percentages of morphologically normal and abnormal sperm varied among individual stallions in both the T and F groups. The mean percentage of morphologically normal sperm was not significantly different (P > 0.05) between T and F stallions (mean +/- SE, 49.7 +/- 1.3 and 48.1 +/- 2.8, respectively). A comparison between the T and F sperm heads revealed that all the dimensional parameters were significantly different (P < 0.05). The coefficients of within-animal variation (CVs) ranged from 2.6 (shape factor 1) to 7.5 (elongation) and 2.9 (shape factor 1) to 8.1 (elongation) in T and F, respectively. In the case of the T group, those sperm head parameters that featured a low within-animal CV and a high between-animal CV were perimeter (2.9, 19.1), shape factor 1 (2.6, 25.8) and shape factor 3 (3.8, 32.0). In the case of the F group, only shape factor 1 (2.9, 26.1) featured such characteristics. We found variability in the percentage of morphologically normal and abnormal sperm, as well as in sperm head dimensions among Thai native crossbred stallions, and these results were similar to those of purebred stallions. Our findings demonstrate that the heads of the T sperm specimens were larger and rounder than that of the F sperm. Perimeter, shape factor 1 and shape factor 3 could be used as parameters for the identification of individual T stallions based on a sperm sample.


Frequency of MYD88 L256P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasm.
B-cell neoplasms are clonal tumors of B cells at various stages of maturation, including diffuse large B-cell lymphoma (DLBCL), chronic lymphocytic lymphoma (CLL), Burkitt lymphoma (BL), lymphoplasmacytic lymphoma (LPL)/Waldenström's macroglobulinemia (WM), splenic marginal zone lymphoma (SMZL), nodal marginal zone lymphoma (NMZL), mantle cell lymphoma (MCL), follicular lymphoma (FL), and hairy cell leukemia (HCL). In this study, we analyzed the frequency of MYD88 L265P mutation and its correlation with clinico-hematological profile in mature B-cell neoplasms. A total of 110 consecutive cases of B-cell neoplasms showing peripheral blood and/or bone marrow infiltration were included. MYD88 L265P mutation was detected by polymerase chain reaction amplification of exon 5 of MYD88 gene, followed by restriction fragment length polymorphism analysis. Among the 110 cases, the major group was of CLL (54.5%, n = 60), followed by HCL. Other cases included MCL, LPL, DLBCL, SMZL, NMZL, FL, and BL. MYD88 L265P mutation was seen in 21 (19.1%) cases of B-cell neoplasm, whereas 89 (80.9%) cases were negative for MYD88 L265P mutation. It was most commonly seen in LPL/WM cases followed by HCL, SMZL, CLL, and MCL cases. No case of DLBCL, FL, and BL showed MYD88 L265P mutation. Statistically significant difference was seen for hemoglobin level in CLL cases, with MYD88 L265P mutated cases showing higher mean hemoglobin levels than MYD88 wild-type cases (p = .001). For other parameters, no statistically significant difference was noted between mutated and unmutated cases. MYD88 L265P mutation is seen in various B-cell neoplasms; it is most commonly seen in LPL/WM cases but not specific for it.


Immune modulatory oligonucleotides in the prevention and treatment of allergen-induced eustachian tube dysfunction in the animal model.
This article reviews the current literature investigating the applications and success of immune modulatory oligonucleotides as immunotherapy to treat and prevent allergen-induced eustachian tube dysfunction in animal models. Synthetic DNA-based immunotherapy agents composed of unmethylated cytosine-guanine dinucleotides (CpG ODNs) that bind to Toll-like receptors have been found to have tremendous potential as therapeutic agents and adjuvants. CpG ODNs can induce a shift in the cytokine profile and immune response that favors the T-helper type 1 pathway and suppresses the T-helper type 2 pathway. This makes CpG ODNs promising candidates for treating allergic diseases. Current CpG ODN studies have demonstrated prevention and treatment of acute allergen inflammation of the eustachian tube in an animal model of otitis media. Immune modulatory oligonucleotides in immunotherapy, administered systemically or topically, have been shown to be safe and effective in the animal model.


Spreading depression requires microglia and is decreased by their M2a polarization from environmental enrichment.
Microglia play an important role in fine-tuning neuronal activity. In part, this involves their production of tumor necrosis factor-alpha (TNFα), which increases neuronal excitability. Excessive synaptic activity is necessary to initiate spreading depression (SD). Increased microglial production of proinflammatory cytokines promotes initiation of SD, which, when recurrent, may play a role in conversion of episodic to high frequency and chronic migraine. Previous work shows that this potentiation of SD occurs through increased microglial production of TNFα and reactive oxygen species, both of which are associated with an M1-skewed microglial population. Hence, we explored the role of microglia and their M1 polarization in SD initiation. Selective ablation of microglia from rat hippocampal slice cultures confirmed that microglia are essential for initiation of SD. Application of minocycline to dampen M1 signaling led to increased SD threshold. In addition, we found that SD threshold was increased in rats exposed to environmental enrichment. These rats had increased neocortical levels of interleukin-11 (IL-11), which decreases TNFα signaling and polarized microglia to an M2a-dominant phenotype. M2a microglia reduce proinflammatory signaling and increase production of anti-inflammatory cytokines, and therefore may protect against SD. Nasal administration of IL-11 to mimic effects of environmental enrichment likewise increased M2a polarization and increased SD threshold, an effect also seen in vitro. Similarly, application of conditioned medium from M2a polarized primary microglia to slice cultures also increased SD threshold. Thus, microglia and their polarization state play an essential role in SD initiation, and perhaps by extension migraine with aura and migraine.


Gamma-glutamyltransferase level in pregnancy is an independent risk factor for gestational diabetes mellitus.
To evaluate the relationship between gamma-glutamyltransferase (GGT) level in pregnant women at oral glucose tolerance test (OGTT) and the diagnosis of gestational diabetes (GDM). Blood was taken for analyzing GGT level from women at high risk of GDM at the time of their scheduled OGTT. GDM was diagnosed according to World Health Organization 1999 criteria. GGT level correlated positively with the 2-hour glucose level (Spearman's rho = 0.112: P < 0.05). GGT values that were stratified into quartiles demonstrated a significant trend with diagnosis of GDM (chi(2) for trend; P = 0.03). Multivariable logistic regression analysis taking into account maternal age, gestational age at OGTT, body mass index and a positive 50-g glucose challenge test (GCT) indicated that high GGT was an independent risk factor for GDM (adjusted odds ratio [AOR] 2.1 95% CI 1.2-3.8: P = 0.01). In the subset of women identified by a positive GCT, on multivariable logistic regression analysis, only high GGT was an independent risk factor for GDM (AOR 2.3 95% CI 1.3-4.2: P = 0.007). Raised GGT level is an independent risk factor for GDM in high risk pregnant women undergoing OGTT.


Significance of anaerobic bacteria in postoperative infection after radical cystectomy and urinary diversion or reconstruction.
Radical cystectomy followed by urinary diversion or reconstruction (RC) is a standard treatment for patients with muscle-invasive bladder cancer. In these operations, a high frequency of complications, especially postoperative infection, has been reported. However, there have only been a few studies about postoperative anaerobic bacterial infection. To clarify the significance and role of anaerobic bacteria in postoperative infection, we retrospectively analyzed cases in which postoperative infection by these organisms developed. A total of 126 patients who underwent RC from 2006 to 2010 were included in this study. Various types of postoperative infection occurred in 66 patients. Anaerobic bacterial infections were detected with cultures for urine and blood in one case, for blood in two cases, and for surgical wound pus in four. The frequency of postoperative anaerobic bacterial infection in RC was less than that of colon surgery. However, this study revealed the possible development of a nonnegligible number of postoperative anaerobic bacterial infections. Therefore, we should consider anaerobic bacteria as possible pathogens in postoperative infection after RC.


Lead effects on non-adrenergic non-cholinergic relaxations in the rat gastric fundus.
The effect of lead exposure on non-adrenergic non-cholinergic (NANC) relaxations in rat gastric fundus was evaluated in this work. Wistar rats were divided into four groups: The control group received tap water and the three other received 0.008% of lead acetate in their drinking water for 15, 30 and 120 days. NANC relaxations induced by electrical field stimulation (0.5-8 Hz, 1 ms, 60 V) of gastric fundus strips was inhibited in all groups treated with lead. The strips from groups, control and 120 days of lead treatment (LEAD 120), were incubated with L-NOARG (100 microM). The presence of this blocker did not produce any additional inhibition. Sodium nitroprusside (10(-10)-10(-6) M) and 8-Br-GMPc (3 x 10(-8)-3 x 10(-4) M) produced dose-dependent relaxations in strips of both groups control and LEAD 120, however, in the LEAD 120, the potencies were significantly reduced from 7.32 +/- 0.05 to 6.40 +/- 0.09 (n = 5) and 4.26 +/- 0.06 to 3.69 +/- 0.05 (n = 5), respectively. Our data suggest that the chronic exposure to lead inhibits NANC relaxations probably by modulating NO release from NANC nerves and/or by interacting with intracellular transducer mechanisms in rat gastric fundus.


Application of maternal plasma DNA analysis for noninvasive prenatal diagnosis of Hb E-beta-thalassemia.
To establish simple noninvasive prenatal diagnosis of common beta-thalassemia in Southeast Asia, we have evaluated the possibility of identifying the 3 most common beta-thalassemia genes [beta(E), beta(17A-T), and beta(41/42(-CTCC))] by analysis of fetal DNA in maternal plasma using combined conventional polymerase chain reaction (PCR) and real-time quantitative PCR. Maternal plasma was obtained from peripheral blood of Thai pregnant women collected during the first and second trimesters of gestation. DNA was prepared from 200 microL plasma using a QIAmp Blood Mini Kit. Identifications of the beta(E), beta(41/42(-CTTT)), and beta(17A-T) in plasma DNA were carried out using semi-nested (for beta(E)) and nested (for beta(41/42) and beta(17)) real-time allele-specific PCR methodologies, and the results were compared with those obtained on fetal tissue analysis with routine invasive procedure. Twenty-six fetal beta(E) genes were correctly identified by maternal plasma DNA analysis of 39 pregnant women investigated. The fetal beta(41/42) and beta(17) mutations were detectable in 6 of 12 and 4 of 9 maternal plasma specimens, respectively, which were in concordance with the results obtained by routine invasive procedure. The noninvasive prenatal diagnostic methods developed should potentially prove useful for detection of paternally inherited mutation and for providing the exclusion of pregnancies at risk for this common genetic disorder in the region.


Slowing with end-stage renal disease: Attentive but unprepared to act.
Dialyzed patients show longer response latencies to stimuli than healthy controls. This study was designed to learn if this abnormal latency may be related to an impairment in the networks that mediate the allocation of sensory-attention (inducing a delay in stimulus recognition-awareness) and/or an impairment of intentional motor preparation (inducing a delay in action-initiation). Dialyzed patients with end-stage renal disease and matched healthy controls were assessed using reaction time tasks from the ROtman-Baycrest Battery to Investigate Attention (ROBBIA) and event-related potentials (ERPs) to help elucidate the possible attentional and/or intentional brain mechanisms that may account for this slowing. The following ERP components were analyzed for single attentional and intentional processes: response preparation (Contingent Negative Variation); perceptual preparation (P1); selective attention and monitoring (P300/Late Positive Potential). Patients (vs. controls) had a decreased ability to sustain response preparation under the condition of a long (3 s) but not a short (1 s) preparation period. This action-intentional deficit was, however, not accompanied by impaired perceptual preparation and monitoring. Future research may investigate whether deficits observed in dialyzed patients can be reduced with treatments such as kidney transplantation.


Characterisation of acyltransferases from Synechocystis sp. PCC6803.
As phylogenetic ancestors of plant chloroplasts cyanobacteria resemble plastids with respect to lipid and fatty acid composition. These membrane lipids show the typical prokaryotic fatty acid pattern in which the sn-2 position is exclusively esterified by C(16) acyl groups. In the course of de novo glycerolipid biosynthesis this prokaryotic fatty acid pattern is established by the sequential acylation of glycerol-3-phosphate with acyl-ACPs by the activity of different acyltransferases. In silico approaches allowed the identification of putative Synechocystis acyltransferases involved in glycerolipid metabolism. Functional expression studies in Escherichia coli showed that sll1848 codes for a lysophosphatidic acid acyltransferase with a high specificity for 16:0-ACP, whereas slr2060 encodes a lysophospholipid acyltransferase, with a broad acyl-ACP specificity but a strong preference for lysophosphatidyglycerol especially its sn-2 acyl isomer as acyl-acceptor. The generation and analysis of the corresponding Synechocystis knockout mutants revealed that lysophosphatidic acid acyltransferase unlike the lysophospholipid acyltransferase is essential for the vital functions of the cells.


Oculo-cerebro-cutaneous syndrome: description of a new case.
A newborn girl is described with the following multiple congenital anomalies: an orbital cyst, cutaneous appendages, focal hypo-aplasia of the skin and multiple cerebral cysts. This case of oculo-cerebro-cutaneous syndrome is compared with four previously published cases.


Essential oil-loaded starch/cellulose aerogel: Preparation, characterization and application in cheese packaging.
Novel antimicrobial emitting aerogels based on starch/cellulose/Thymus daenensis Celak essential oil (SC-TDEO) were developed and optimized for antimicrobial packaging of Koopeh cheese. An aerogel formulation containing cellulose (1 %; extracted from sunflower stalks) and starch (5 %) in a 1:1 ratio was selected for in vitro antimicrobial assay and subsequent cheese application. The minimum inhibitory dose (MID) of TDEO in the vapor phase against Escherichia coli O157:H7 was determined by loading various concentrations of TDEO onto the aerogel, and an MID of 256 μL/Lheadspace was recorded. Aerogels containing TDEO at 25 × MID and 50 × MID were then developed and used for cheese packaging. During a 21-day storage period, cheeses treated with SC-TDEO50 MID aerogel exhibited a significant 3-log reduction in psychrophile counts and a 1-log reduction in yeast-mold counts. Moreover, significant changes in the population of E. coli O157:H7 were observed in cheese samples. After 7 and 14 days of storage with SC-TDEO25 MID and SC-TDEO50 MID aerogels, the initial bacterial count became undetectable, respectively. Sensory evaluations indicated that the samples treated with SC-TDEO25 MID and SC-TDEO50 aerogels received higher scores compared to the control group. These findings demonstrate the potential of the fabricated aerogel to develop antimicrobial packaging suitable for cheese applications.


Obstetric laceration repair in the United States: is there a common practice?
To assess practice preferences in the repair of severe obstetric lacerations among obstetrician/gynecologists in the United States. A survey detailing third and fourth degree laceration repair techniques was distributed to 634 obstetrician/gynecologists from demographically diverse areas of the United States. Categorical outcomes were compared among respondents using chi2 or Fisher's exact test where appropriate. Of the 266 respondents, there were 124 self-reported "experts" (47%) and 106 physicians-in-training (40%). Repair techniques were compared between experts versus nonexperts and trainees versus practicing physicians. There were no significant differences found between either comparison group on the type and size of suture utilized or preferred method of closure for repair. There is little variation in the practice pattern of complex laceration repairs among obstetrician-gynecologists in the United States. This commonality should encourage the design of standard teaching models and techniques for physicians in training.


Ranitidine maintenance therapy in the prevention of duodenal ulceration; a comparison of 150 mg at night with 300 mg at night.
The purpose of this study was to investigate if the use of a higher night time dose of ranitidine (300 mg) could keep significantly more duodenal ulcer patients in remission than the usual maintenance dose (150 mg). Double-blind, multi-centre, parallel group study of patients with proven healed duodenal ulcer randomized to ranitidine 150 mg or 300 mg daily for 1 year. The primary study end-point was symptomatic, endoscopically proven ulcer relapse. A total of 489 patients were recruited into the study. The endoscopically proven relapse rates were 6.1% of ranitidine 150 mg daily (n = 250) and 6.9% on 300 mg daily (n = 239). These differences were not statistically significant. This study provides further evidence that maintenance therapy with ranitidine 150 mg daily is highly effective at preventing duodenal ulcer relapse. The use of the higher dose of 300 mg daily does not appear to keep significantly more patients in remission.


Tat-SIRT1 tango.
In a recent issue of Cell Host & Microbe, Kwon et al. (2008) report that the human immunodeficiency virus (HIV) transactivator Tat inhibits the SIRT1 deacetylase, resulting in increased acetylation of the NF-kappaB p65 subunit and subsequently in T cell hyperactivation.


Ethinylestradiol and levonorgestrel preparations on the Belgian market: a comparative study.
Preparations formulated as coated or film-coated tablets, containing levonorgestrel and the combination ethinylestradiol/levonorgestrel, were evaluated in a comparative study. This study comprised in vitro dissolution, assay and content uniformity. The analytical methods were previously validated according to international guidelines. All examined products complied with the postulated requirements.


Preparation of a novel poly-(di-ionic liquid)/BDD-modified electrode for the detection of tetrachloro-p-benzoquinone.
During the COVID-19 pandemic, the release of toxic disinfection by-products (DBPs) has increased due to the intensive, large-scale use of disinfectants. Halogenated benzoquinones (HBQs) are among the most toxic DBPs, but there is no rapid, convenient, and economical detection method. In this study, a novel PDIL/BDD-modified electrode was prepared in a mixed solvent of dimethyl sulfoxide (DMSO) and acetonitrile (ACN) by electrochemical polymerization with a di-ionic ionic liquid containing alkenyl groups as the monomer. The electrochemical behavior of tetra-chloro-p-benzoquinone (TCBQ) on the modified electrode was studied. By studying the cyclic voltammetry behavior of TCBQ on the PDIL/BDD electrode, it was concluded that the electrode reactions of TCBQ included the reduction of TCBQ to TCBQH2 (C1) and the reduction of bis-quinhydrone imidazole π-π type charge transfer complex to TCBQH2 (C2). By studying the SWV responses of TCBQ in the concentration range of 1-100 ng/L on the PDIL/BDD electrode, it was found that the reduction peak current (Ipa) had a linear relationship with the concentration. The electrochemical SWV technique was used to detect the concentration of trace TCBQ in water and is expected to be used for the detection of other HBQs in drinking water and swimming pool water.


Targeting gut barrier dysfunction with phytotherapies: Effective strategy against chronic diseases.
The intestinal epithelial layer serves as a physical and functional barrier between the microbe-rich lumen and immunologically active submucosa; it prevents systemic translocation of microbial pyrogenic products (e.g. endotoxin) that elicits immune activation upon translocation to the systemic circulation. Loss of barrier function has been associated with chronic 'low-grade' systemic inflammation which underlies pathogenesis of numerous no-communicable chronic inflammatory disease. Thus, targeting gut barrier dysfunction is an effective strategy for the prevention and/or treatment of chronic disease. This review intends to emphasize on the beneficial effects of herbal formulations, phytochemicals and traditional phytomedicines in attenuating intestinal barrier dysfunction. It also aims to provide a comprehensive understanding of intestinal-level events leading to a 'leaky-gut' and systemic complications mediated by endotoxemia. Additionally, a variety of detectable markers and diagnostic criteria utilized to evaluate barrier improving capacities of experimental therapeutics has been discussed. Collectively, this review provides rationale for targeting gut barrier dysfunction by phytotherapies for treating chronic diseases that are associated with endotoxemia-induced systemic inflammation.


New aspects in spinal diagnostics with 3-D computed tomography.
Three-dimensional imaging in computer tomography (3-D CT) has been rendered feasible by the development of special software programs. On the basis of the data from 50 spinal CTs, 3-D reformations are made. The method has proved effective especially in complicated vertebral fractures. There are regular correlations between the plane of the fracture and the choice of the axis of rotation as well as the nature of the reformations. A 3-D reformation is frequently more appropriate than a coronary or a sagittal 2-D reformation. In destructions of vertebrae due to tumors, the extent of bone destruction and the altered position of the vertebrae in relation to each other can be imaged. 3-D computer tomograms do not provide fundamentally new diagnostic information, but the understanding of pathological topography is improved.


Assessing the standards of online oral hygiene instructions for patients with fixed orthodontic appliances.
The authors conducted this study to assess the quality of the information available on the Web about oral hygiene for patients with fixed orthodontic appliances. The authors entered the search terms "cleaning braces," "brushing braces," and "oral hygiene and braces" into Google, Yahoo, and Bing search engines. They analyzed Web sites satisfying the inclusion criteria from the first 20 hits of each search for accessibility, usability, and reliability by using the LIDA instrument; for readability by using the Flesch Reading Ease (FRE) score; and for the completeness of oral hygiene instructions. Sixty-two Web sites met the inclusion criteria. The mean total LIDA score of 71.2 indicated the moderate quality of the design of the reviewed Web sites. The mean (standard deviation [SD]) values of LIDA scores for accessibility, usability, and reliability were 85.9 (7.0), 63.4 (16.1), and 48.0 (10.4), respectively. The mean (SD) FRE Score of 68.6 (9.7) applied to standard reading skills. The completeness of information (mean [SD] = 67.1 [27.8]) presented the highest variability. Overall, the authors found that the standards of online oral hygiene materials for orthodontic patients with fixed appliances exhibited modest scores. Readability appeared to be appropriate for young adolescents, whereas the comprehensiveness of the displayed information was highly variable. Further improvement of the infrastructure of electronic health information (that is, e-health) in orthodontics is necessary to meet patients' needs. Given the moderate quality of oral hygiene instruction available on the Web for patients with fixed appliances, orthodontic patients and caregivers should be cautious when browsing the Internet for relevant information. Dental professionals should refer patients to valid Web-based educational materials.


A remote sensing study of spatiotemporal variations in drought conditions in northern Asir, Saudi Arabia.
Changes in vegetation land cover are influenced by, and therefore an indicator of, climatic conditions. The aim of this study is to investigate the relationship between vegetation cover changes and drought events in a small-scale area. Six Landsat images during 1987-2019 were used to extract information about the vegetation land cover changes using the normalized difference vegetation index (NDVI) and the fractional vegetation cover (FVC) in Balqarn Governorate in the northern mountains of Asir, Saudi Arabia. Two climatic parameters, temperature and precipitation, were used as time series for the same period and were decomposed to investigate the seasonal and trend changes for each parameter. The two parameters were also used to calculate the standardized precipitation evapotranspiration index (SPEI) to conduct an in-depth analysis of the drought events influencing vegetation cover. The results showed that the state of the vegetation coverage of the study area remained at a medium level with an average NDVI value, but the FVC values showed evidence of dynamic variability associated with drought and moisture events. The SPEI showed that the study area has been undergoing a long-duration drought event since 2004, ranging from light to severe drought, which was consistent with the time series decomposition results. This investigation has revealed that drought drives changes in vegetation cover and is expressed on small geographic scales as changes in the vegetation cover structure. The framework described here is simple and can be used to evaluate and manage drought risks.


Development and validation of a stable-isotope dilution liquid chromatography-tandem mass spectrometry method for the determination of bisphenols in ready-made meals.
Due to their growing consumption, ready-made meals are a major dietary component for many people in today's society, representing an important potential route of human exposure to several food contaminants. The recent restrictions in the use of bisphenol A have led the plastic industry to look for alternative chemicals, most of them belonging to the same family of p,p'-bisphenols. The aim of the current work was to develop and validate a method based on stable-isotope dilution liquid chromatography-tandem mass spectrometry for the analysis of bisphenol A and its main analogs - bisphenol S, 4,4'-sulfonylbis(2-methylphenol), bisphenol F, bisphenol E, bisphenol B, bisphenol Z, bisphenol AF, bisphenol AP, tetrabromobisphenol A and bisphenol P - in solid foodstuffs, and particularly in ready-made meals. Extraction was carried out by ultrasound-assisted extraction after sample disruption with sand. A selective solid-phase extraction procedure was then applied to reduce potential matrix interferences. Derivatization of bisphenols with pyridine-3-sulfonyl chloride increased their ionization efficiency by electrospray ionization. Validation of the proposed method was performed in terms of selectivity, matrix effects, linearity, precision, measurement uncertainty, trueness and limits of detection. Satisfactory repeatability and intermediate precision were obtained; the related relative standard deviations were ≤7.8% and ≤10%, respectively. The relative expanded uncertainty (k=2) was below 17% for all bisphenol analogs and the trueness of the method was demonstrated by spike recovery experiments. Low limits of detection, in the range from 0.025μgkg(-1) to 0.140μgkg(-1), were obtained for all compounds. To demonstrate the applicability of the proposed method, it was eventually applied to several ready-made meals purchased from different supermarkets in Belgium.


[Determination of DON-3-Glucoside in artificially and naturally contaminated wheat with LC-MS/MS].
Naturally contaminated and artificiallyFusarium spp. inoculated wheat was analyzed for deoxynivalenol, deoxynivalenol-3-glucoside, 3-acetyl-deoxynivalenol and 15-acetyl-deoxynivalenol. After extraction and clean-up with MycoSep columns, the trichothecenes were determined using a LC-ESI-MS/MS method. Deoxynivalenol-3-glucoside was detectable in 4 out of 4 artificially inoculated and in 22 out of 25 naturally contaminated wheat samples. For the latter, the average relative deoxynivalenol-3-glucoside concentration was about 6% of the deoxynivalenol concentration. The maximum relative deoxynivalenol-3-glucoside concentration was 12% as compared to the concentration of deoxynivalenol. In all samples, the concentration of deoxynivalenol-3-glucoside was higher than the concentrations of 3-acetyl-deoxynivalenol or 15-acetyl-deoxynivalenol.


[Pharaoh ants in a ward for premature infants].
Pharaoh's ants (Monomorium pharaonis) appeared in a children's hospital and wounded the skin of the pre-mature births. Possibilities for control are discussed.


Watchful waiting vs repair for asymptomatic or minimally symptomatic inguinal hernia in men: a systematic review.
One-third of patients presenting with inguinal hernia are asymptomatic and the best treatment for these patients is unclear. The aim of this study was to assess the feasibility of applying a watchful waiting strategy for asymptomatic or minimally symptomatic inguinal hernia in men. PubMed, EMBASE, and Cochrane Library were searched from database inception to May 14, 2020. Included were all types of original data written in English, German, Danish, Swedish, or Norwegian involving ≥ 5 male patients aged ≥ 18 years old with asymptomatic or minimally symptomatic inguinal hernia and undergoing watchful waiting. This review was reported according to the PRISMA guideline. A total of nine studies were included; three randomized controlled trials, three prospective cohort studies, and three retrospective cohort studies. Data on a total of 858 unique patients following a watchful waiting strategy were included. Approximately one-third of patients crossed over from watchful waiting to surgery after 3 years increasing to more than two-thirds after 10 years. The most frequent reason for crossover was hernia-related pain (median 79%, range 48-91%). The rate of acute hernia-related operations was low (2-3%), and watchful waiting was not associated with increased mortality or postoperative complications. Levels of pain and discomfort after randomization were similar over time between patients undergoing elective repair or watchful waiting. Applying a watchful waiting strategy to men with asymptomatic or minimally symptomatic inguinal hernia was safe, but two-thirds of patients crossed over to surgical repair within 10 years mainly due to pain.


Arm anthropometry in a large reference population and in surgical patients.
Triceps skinfold (TSF) and midarm circumference (MAC) were measured and the arm muscle circumference (AMC) calculated in 1860 healthy persons aged between 20 and 101 years and because the distribution of our findings was not Gaussian we have used the 5th and 10th percentiles instead of standard deviation to define limits between severe and moderate malnutrition and between moderate malnutrition and normal. One-way variance analysis showed significant increases in TSF in women from the 3rd (mean 18.3 mm) to the 6th (mean 23.6 mm) decades (p<0.05 - 0.001). No variation was seen in the 6th and 7th decades but thereafter decreases occurred to the 10th (mean 14.4 mm) decade (p<0.05 - 0.001). In men, TSF showed no variation from the 3rd (mean 10.8 mm) to the 9th (mean 10.6 mm) decades but in the 10th (mean 9.4 mm) decade it decreased significantly (p<0.05). In women, AMC increased from the 3rd (mean 21.1 cm) to the 6th (mean 22.1 cm) decades (p<0.05 - 0.001). No variation was seen from the 6th to 8th decades, but thereafter decreases occurred to the 10th (mean 20.2 cm) decade (p<0.05 - 0.001). In men no variation was seen in AMC from the 3rd (mean 26.2 cm) to the 7th (mean 25.9 cm) decades, but decreases were shown to the 10th (mean 23.0 cm) decade (p<0.001). Using these values in 112 surgical patients, 26 per cent showed signs of malnutrition in their fat stores and 6 per cent in muscle. The wide variation in anthropometric measurements between different age groups precludes the use of a mean reference value covering all ages in the assessment of malnutrition.


Mapping heterogeneity of cellular mechanics by multi-harmonic atomic force microscopy.
The goal of mechanobiology is to understand the links between changes in the physical properties of living cells and normal physiology and disease. This requires mechanical measurements that have appropriate spatial and temporal resolution within a single cell. Conventional atomic force microscopy (AFM) methods that acquire force curves pointwise are used to map the heterogeneous mechanical properties of cells. However, the resulting map acquisition time is much longer than that required to study many dynamic cellular processes. Dynamic AFM (dAFM) methods using resonant microcantilevers are compatible with higher-speed, high-resolution scanning; however, they do not directly acquire force curves and they require the conversion of a limited number of instrument observables to local mechanical property maps. We have recently developed a technique that allows commercial AFM systems equipped with direct cantilever excitation to quantitatively map the viscoelastic properties of live cells. The properties can be obtained at several widely spaced frequencies with nanometer-range spatial resolution and with fast image acquisition times (tens of seconds). Here, we describe detailed procedures for quantitative mapping, including sample preparation, AFM calibration, and data analysis. The protocol can be applied to different biological samples, including cells and viruses. The transition from dAFM imaging to quantitative mapping should be easily achievable for experienced AFM users, who will be able to set up the protocol in <30 min.


Splenic rupture as the presenting manifestation of primary splenic angiosarcoma in a teenage woman: a case report.
Primary splenic angiosarcoma is a rare neoplasm of vascular origin carrying a very poor prognosis, partly due to its high metastatic potential. This disease presents frequently with splenic rupture and hemorrhage. We report the case of a 17-year-old woman who presented with rupture of a primary splenic angiosarcoma. The patient presented with diffuse abdominal pain and distention. Clinical examination revealed severe tenderness in the left upper abdominal quadrant, a palpable abdominal mass, and hemodynamic instability with a systolic arterial blood pressure of 75 mmHg and heart rate of 135 beats per minute. Blood tests revealed anemia (hemoglobin 7.0 g/dl) and thrombocytopenia (platelets 70 x 109/liter). After initial fluid resuscitation and stabilization, abdominal ultrasound and computed tomography were performed, revealing a large quantity of intraperitoneal free fluid, an enlarged spleen, and a heterogeneous low-density signal within the splenic parenchyma, which showed varying degrees of contrast enhancement. At laparotomy a huge (weight 1530 g, diameter 19 cm) actively bleeding spleen was identified and splenectomy was performed. Histopathology showed a primary splenic angiosarcoma. After an uneventful recovery, the patient was discharged on the sixth postoperative day. Primary splenic angiosarcoma is rare. Although this malignancy is usually encountered in advanced age, there have been a few reported cases among younger patients. The case reported here presented with splenic rupture, was treated by laparotomy and splenectomy, and the patient is disease free 16 months after surgery.


Molecular and clinical diversity in primary central nervous system lymphoma.
Primary central nervous system lymphoma (PCNSL) is a rare and distinct entity within diffuse large B-cell lymphoma presenting with variable response rates probably to underlying molecular heterogeneity. To identify and characterize PCNSL heterogeneity and facilitate clinical translation, we carried out a comprehensive multi-omic analysis [whole-exome sequencing, RNA sequencing (RNA-seq), methylation sequencing, and clinical features] in a discovery cohort of 147 fresh-frozen (FF) immunocompetent PCNSLs and a validation cohort of formalin-fixed, paraffin-embedded (FFPE) 93 PCNSLs with RNA-seq and clinico-radiological data. Consensus clustering of multi-omic data uncovered concordant classification of four robust, non-overlapping, prognostically significant clusters (CS). The CS1 and CS2 groups presented an immune-cold hypermethylated profile but a distinct clinical behavior. The 'immune-hot' CS4 group, enriched with mutations increasing the Janus kinase (JAK)-signal transducer and activator of transcription (STAT) and nuclear factor-κB activity, had the most favorable clinical outcome, while the heterogeneous-immune CS3 group had the worse prognosis probably due to its association with meningeal infiltration and enriched HIST1H1E mutations. CS1 was characterized by high Polycomb repressive complex 2 activity and CDKN2A/B loss leading to higher proliferation activity. Integrated analysis on proposed targets suggests potential use of immune checkpoint inhibitors/JAK1 inhibitors for CS4, cyclin D-Cdk4,6 plus phosphoinositide 3-kinase (PI3K) inhibitors for CS1, lenalidomide/demethylating drugs for CS2, and enhancer of zeste 2 polycomb repressive complex 2 subunit (EZH2) inhibitors for CS3. We developed an algorithm to identify the PCNSL subtypes using RNA-seq data from either FFPE or FF tissue. The integration of genome-wide data from multi-omic data revealed four molecular patterns in PCNSL with a distinctive prognostic impact that provides a basis for future clinical stratification and subtype-based targeted interventions.


Expression of genes of lipid synthesis and altered lipid composition modulates L-glutamate efflux of Corynebacterium glutamicum.
L-Glutamate is made with Corynebacterium glutamicum on a scale of more than 106 tons/year. Nevertheless, formation of this amino acid is enigmatic and there is very limited molecular information available to unravel the apparently complex conditions leading to L-glutamate efflux. Here, we report the isolation and overexpression of the genes involved in lipid synthesis: acp, fadD 15, cma, cls, pgsA2, cdsA, gpsA, and plsC, and the inactivation of cma and cls. In addition, the consequences for phospholipid content, temperature sensitivity, as well as detergent-independent and detergent-dependent L-glutamate efflux were quantified. An in part strong alteration of the phospholipid composition was achieved; for instance, overexpression offadD15 encoding an acyl-CoA ligase resulted in an increase of phosphatidyl inositol from 12.6 to 30.2%. All strains, except that overexpressing acp (acyl carrier protein), exhibited increased temperature sensitivity, with the strongest sensitivity present upon cls (cardiolipin synthetase) inactivation. As a consequence of the genetically modified lipid synthesis, L-glutamate efflux changed quite dramatically; for instance, overexpression of plsC (acylglycerolacyl transferase) resulted in a detergent-triggered increase of L-glutamate accumulation from 92 mM to 108 mM, whereas acp overexpression reduced the accumulation to 24 mM. With some of the overexpressed genes, substantial L-glutamate excretion even without detergent addition was obtained when the fermentation temperature was elevated. These data show that the chemical and physical properties of the cytoplasmic membrane are altered and suggest that this is a necessary precondition to achieve L-glutamate efflux.


The Association of Subspecialty and Sex with Industry Payments to Internal Medicine Physicians Who Recently Completed Training.
Financial relationships with drug and medical device companies may impact quality of care and academic research. However, little is known when and how these financial relationships develop among newly independent physicians who recently completed from residency or fellowship programs in internal medicine (IM). To compare patterns of industry payments among IM graduates. Retrospective, observational cohort study. IM graduates from residency or fellowship programs between January 2015 and December 2019. We analyzed Open Payments reports made between July 2015 and June 2021 to recent graduates of U.S. Accreditation Council for Graduate Medical Education (ACGME)-accredited residency and fellowship programs in IM. The primary outcome was general payments accepted by these physicians, stratified by procedural (i.e., critical care medicine/pulmonary medicine, cardiac/cardiovascular disease, and gastroenterology) and non-procedural (i.e., infectious disease, general internal medicine, and other specialties) subspecialties. The secondary outcomes included general payments stratified by sex and age at residency or fellowship training completion. There were 41,669 IM physicians with a median age of 33.0 years. In the first 3 years after completion, the proportion of physicians accepting any general payments was 72.6%, 91.9%, and 86.8% in Critical Care Medicine/Pulmonary Medicine, Cardiac/Cardiovascular Disease, and Gastroenterology, compared to 56.1%, 52.6%, and 52.3% in Infectious Disease, General Internal Medicine, and Other Specialties (p<0.0001). After adjusting for confounding variables, the procedural group showed an increased hazard ratio (HR) for accepting any general payments and at least $5000 of general payments compared to the non-procedural group. The HRs of accepting any general payments in the procedural subspecialty were 2.26 (95% CI, 2.11-2.42) and 2.83 (95% CI, 2.70-2.97) in female and male physicians, respectively (p-value < 0.0001). Industry financial relationships among newly independent physicians in IM exist immediately after completion of training and are influenced by subspecialty, sex, and age.


Protein content and composition of human high density lipoprotein subfractions.
High density lipoprotein (HDL) was fractionated by ion exchange column chromatography using a continuous NaCl gradient of 0.06--0.13 M. It was found that, on the basic C apoprotein content, HDL is comprised of 3 subfractions. All 3 subfractions contain apo A-I and apo A-II but the apo A-I/apo A-II ratio is different in each subfraction and in the case of subfraction c, that fraction which eluted at highest NaCl concentrations, the A-I/A-II ratio varied even within this subfraction. Subfraction a contained no C apoprotein, subfraction b contained apo C-II and apo C-III-1 but no apo C-III-2 while subfraction c contained apo C-III-2 and trace amounts of apo C-II and C-III-1. Analysis of HDL2 and HDL3 shows that both contain all 3 lipoprotein subfractions, but in differing quantities.


Wrinkles due to idiopathic loss of mid-dermal elastic tissue.
Widespread areas of fine wrinkling of the skin had been noted for 2 years by a 42-year-old healthy white woman. Histological study disclosed a selective absence of elastic tissue strictly limited to the mid-dermis of the involved areas. It was postulated that an antecedent urticarial process may have led to such a specific zonal destruction of elastic tissue. The elastolytic process did not change or extend, and no urticarial lesions were seen during a year of observation.


The Effect of Maternal Death on the Health of the Husband and Children in a Rural Area of China: A Prospective Cohort Study.
To examine the effects of maternal death on the health of the index child, the health and educational attainment of the older children, and the mental health and quality of life of the surviving husband. A cohort study including 183 households that experienced a maternal death matched to 346 households that experienced childbirth but not a maternal death was conducted prospectively between June 2009 and October 2011 in rural China. Data on household sociodemographic characteristics, physical and mental health were collected using a quantitative questionnaire and medical examination at baseline and follow-up surveys. Multivariate linear regression, logistic regression models and difference-in-difference (DID) were used to compare differences of outcomes between two groups. The index children who experienced the loss of a mother had a significantly higher likelihood of dying, abandonment and malnutrition compared to children whose mothers survived at the follow-up survey. The risk of not attending school on time and dropping out of school among older children in the affected group was higher than those in the control group during the follow-up. Husbands whose wife died had significantly lower EQ-5D index and EQ-VAS both at baseline and at follow-up surveys compared to those without experiencing a wife's death, suggesting an immediate and sustained poorer mental health quality of life among the surviving husbands. Also the prevalence of posttraumatic stress disorder (PTSD) was 72.6% at baseline and 56.2% at follow-up among husbands whose wife died. Maternal death has multifaceted and spillover effects on the physical and mental health of family members that are sustained over time. Programmes that reduce maternal mortality will mitigate repercussions on surviving family members are critical and needed.


Empirical relations among scattering, roughness parameters, and thickness of aluminum films.
Experimental measurements of the angular distribution of scattering and scanning electron microscopy pictures of thin aluminum films were used to relate the total integrated scattering and the statistical parameters of the surface roughness to the film thickness.


A randomized clinical trial investigating perceived burdensomeness as a mediator of brief intervention effects on posttraumatic stress symptoms.
Posttraumatic stress disorder (PTSD) is a prevalent and impairing condition that often involves difficulties with interpersonal functioning. Targeting interpersonal difficulties may be a promising alternative approach to reducing PTSD symptoms, particularly given the relatively low rates of treatment engagement and efficacy for first-line treatments for PTSD. Recent research has identified perceived burdensomeness (i.e., feelings of being a burden on others) and thwarted belongingness (i.e., feeling isolated and as if one does not belong) as two specific interpersonal factors related to increased PTSD symptoms. Thus, the current study tested whether a brief, computerized intervention would reduce PTSD symptoms via reductions in perceived burdensomeness and thwarted belongingness, vs. a repeated contact control condition. Hypotheses were tested among 250 trauma-exposed participants who were randomized to receive one of two active computerized interventions designed to target interpersonal factors (i.e., perceived burdensomeness or thwarted belongingness) or anxiety sensitivity, or participate in a repeated contact control condition, as part of a larger randomized clinical trial. Participants were then followed over six-months. Results indicated a direct effect of the active interventions on PTSD symptoms at month-one, that was not detected at months three or six. However, there was a significant indirect effect of condition at all-time points, such that reductions in perceived burdensomeness mediated condition effects on PTSD symptoms. Findings identify perceived burdensomeness as a potential etiological factor in the maintenance of PTSD symptoms, and suggest that targeting perceived burdensomeness may be an effective approach to reducing PTSD symptoms.


Age-Dependent Pharmacokinetics of Doxorubicin in Children with Cancer.
Knowledge on the pharmacokinetics of doxorubicin, especially in children, is very limited with conflicting evidence concerning a possible age dependency in the pharmacokinetics. The aim of the current investigation was to assess, by using population pharmacokinetics, whether an age dependency in the clearance (CL) of doxorubicin exists. Pharmacokinetic data of doxorubicin and its main metabolite doxorubicinol from 94 children (aged 0-18 years) from the EPOC-MS-001-Doxo trial were available. A population pharmacokinetic model was developed in NONMEM(®) 7.2.0. A linear three-compartment model for doxorubicin, with one additional compartment for doxorubicinol, gave the best fit to the data. All model parameters were linearly scaled on body surface area. Including a power function of age as a covariate for CL led to a further improvement of the model. Variation in genes encoding for enzymes involved in the metabolism or active transport of doxorubicin had no influence on the pharmacokinetics. Estimates of CL were lower (26.6 L/h/m(2) in children aged >3 years and 21.1 L/h/m(2) in children aged ≤3 years, p = 0.0004) in children aged <3 years, compared with older children. This is the first model to describe the pharmacokinetics of doxorubicin in children, with a specific focus on infants and children aged <3 years. The lower CL in younger children should be considered together with the pharmacodynamics, especially the cardiotoxicity, when selecting the dose for future protocols.


Chemotherapy and Targeted Therapy Strategies in Patients with Unresectable or Borderline Resectable Metastatic Colorectal Cancer: Evidence for a Lack of Focus on Resection Rates.
Chemotherapy (CTx) with targeted therapy (TT) have increased the overall response rate (ORR) and improved survival in unresectable or borderline resectable metastatic colorectal cancer (mCRC). However, the resection rate is an endpoint with often suboptimal expert involvement. The aim was to investigate whether the improvements in ORR have translated to improved resection rates (RR). A systematic literature search was performed using the PICO process. Odds ratios, and 95% confidence intervals (OR, 95% CI) were analyzed for ORR and RR using dichotomous values with the Mantel-Haenszel method. Progression-free survival (PFS) and overall survival (OS) were analyzed using the inverse-variance method and displayed as hazard ratios and 95% confidence intervals (HR, 95% CI). The literature search returned 469 records. Sixteen articles with 5724 patients were selected for analysis. The qualitative analysis revealed low and moderate risk of bias endpoints. Higher ORR was observed with CTx + TT versus CTx only (OR: 0.62 [95% CI 0.45; 0.82], p = 0.002) and with triplet CTx + TT versus doublet CTx + TT (OR: 0.61 [95% CI 0.46; 0.81], p < 0.001). PFS and OS were improved by use of TT (HR: 0.68-0.84; p < 0.001 to 0.04). The overall RR was low (< 15%) and did not improve in the same way as the other endpoints. The ORR and survival rates in unresectable and borderline resectable mCRC were improved by modern CTx and TT that did not translate into higher RR, mostly due to the lack of expert involvement.


Use and Safety of Viscum album L Applications in Cancer Patients With Preexisting Autoimmune Diseases: Findings From the Network Oncology Study.
Viscum album L (VA, mistletoe) extracts are commonly used in integrative oncology. Here the clinical safety profile of additional VA-treatments to standard care in cancer patients with preexisting autoimmune diseases was analyzed. In this observational cohort study medical data and recorded adverse events (AEs) of treated patients were retrieved from the Network Oncology registry and a safety analysis was performed. A total of 106 patients (median age 63 years) treated with add-on VA-extracts were analyzed. Most frequent autoimmune diseases were Hashimoto's thyroiditis (27%), psoriasis (19%), and ulcerative colitis (15%). Seventeen patients (16%) experienced VA-related AEs, but neither long-term side effects nor VA-therapy discontinuations were recorded. In a subgroup of 30 patients receiving long-term VA-therapy no exacerbations or flares of underlying autoimmune diseases were recorded. Additionally, a significant halving of overall AE-rates was observed during VA-treatment periods (p= 0.019). Our findings suggest that add-on VA-therapy in cancer patients with preexisting autoimmune diseases as Hashimoto's thyroiditis, psoriasis, ulcerative colitis, Grave's disease, and some rheumatic diseases is safe. No higher rates of VA-associated AEs were observed and the overall AE-rates were significantly lowered in VA-therapy periods. However, results should be interpreted with caution in light of the study's observational character.


Assessing Quality of Working Life Among Malaysian Workers.
The Work-Related Quality of Life Scale-2 (WRQLS-2) has been used to measure quality of working life (QOWL) in the United Kingdom. In this study, the scale was translated and normalized into Malay. The scale was translated using the back-translation method, pretesting, and pilot testing. It was conducted among health care and office workers. It was tested in 3 stages; confirmatory factor analysis at stages 1 and 3 and exploratory factor analysis at stage 2. The Malaysian WRQLS-2 had 5 factors: "General Well-Being," "Job and Career Satisfaction," "Employee Engagement," "Home-Work Interface," and "Stress at Work." The scale showed good convergent and construct validity and also reliability. Perception of good QOWL may differ because of cultural influences and varying work environments. The validated Malaysian WRQLS-2 can be used to determine the QOWL of Malaysian office and health care workers.


Bacterial interactions in the nasopharynx - effects of host factors in children attending day-care centers.
The nasopharynges of preschool children are often colonized by potentially pathogenic bacteria. The interactions between these common pathogens and certain host factors were investigated in healthy preschool children 1-6 years of age. Nasopharynx samples were collected from all 63 children attending a day-care center that experienced an outbreak of penicillin-resistant Streptococcus pneumoniae. The samples were analyzed for S. pneumoniae, Haemophilus influenzae, Moraxella catarrhalis, and Group A Streptococci. A model for the risk of carrying these bacteria was established using logistic regression. S. pneumoniae and H. influenzae antagonize each other, whereas M. catarrhalis and S. pneumoniae have a positively association. The risk of carrying M. catarrhalis decreases with age. The time spent in day care each week was not shown to influence the rate of carriage of any of these pathogens. The negative effect of H. influenzae on S. pneumoniae is discussed in relation to the carriage of penicillin-resistant S. pneumoniae, and possible mechanisms involved in this interaction are presented.


A dynamic binomial sequential sampling plan for Plutella xylostella (Lepidoptera: Plutellidae) on broccoli and cauliflower in Australia.
Binomial sequential sampling plans have been used widely for monitoring invertebrate pest populations. Such plans are typically based upon a single action threshold (AT), which represents the level of infestation that the grower is prepared to accept before using a control measure. For many cropping systems this acceptable infestation level is likely to vary, being dependent on factors such as the growth stage of the crop and the value or demands of the destination market (e.g., local or high-quality export). We developed and validated a computer-assisted plan that uses a dynamic AT. The plan has been developed for monitoring diamondback moth, Plutella xylostella (L.) on broccoli (Brassica oleracea variety botrytis L.) and cauliflower (Brassica oleracea variety botrytis L.), but the concepts and methodologies could be readily applied to other systems.


Predictors of Primary Care Practice Among Medical Students at the Michigan State University College of Human Medicine.
This study examines the evolution of student and physician interest in primary care from medical school matriculation to practice, focusing on student factors that potentiate primary care (PC) practice. We compiled a dataset of 2,047 Michigan State University College of Human Medicine graduates from 1991 to 2010. PC interest was assessed using the Association of American Medical Colleges (AAMC) matriculating student (MSQ) and graduation (GQ) questionnaires. PC practice was determined using AMA physician Masterfile data. C2 analyses and logistic regression were used to examine factors that predict PC practice. PC interest at matriculation and at graduation were the factors most likely to predict PC practice. After controlling for URM status, gender, and rural origin, the odds of practicing PC among those with a sustained interest in PC (on both the MSQ and GQ) were 100 times higher than those with no interest in PC, on either survey (P < .01). Among those students who developed an interest in PC by graduation, the odds of practicing PC were 60 times higher than noninterested students (P < .01). Finally, among students who were interested in PC at matriculation, but not graduation, the odds of eventually practicing PC were 3.8 times higher than noninterested students (P < .01). Our study suggests that cultivating PC interest at any point during medical school may predict PC practice. Early and sustained interest in primary care was the most substantial predictor of PC practice in our study, highlighting the need for primary care education even before medical school matriculation.


A School-Based Intervention Using Health Mentors to Address Childhood Obesity by Strengthening School Wellness Policy.
The objective of our study was to strengthen wellness policy in Title 1 schools by implementing a mentored behavior-change model that extends the continuum of care from academic to community settings and mobilizes existing public resources in accordance with US Preventive Services Task Force screening guidelines for childhood obesity management. Team Kid POWER! (KiPOW!) health mentors (students and trainees in medical and health-related fields) in 2 geographically and demographically distinct school districts, the District of Columbia and Orange County, California, delivered standardized health curricular modules to fifth grade classrooms, modeled healthy eating behaviors during school lunchtime, and engaged in active play at recess. Initial interventions in the the District of Columbia and Orange County delivered 10 sessions in which all participants received the intervention. Two subsequent interventions in Orange County, for 5 weeks (Lite) and 10 weeks (Full), included controls. Pre-post measurements of body mass index (BMI) and blood pressure were documented in all participants. A mixed linear regression model, which included a random effect for each school, estimated differences between Full and Lite interventions compared with controls, adjusting for site, sex, and baseline status of the dependent variable. KiPOW! Full, but not KiPOW! Lite, was associated with a modest reduction in BMI percentile compared with control (KiPOW! Full, P = .04; KiPOW! Lite, P = .41), especially in Orange County (P < .001). Systolic blood pressure improved in Full (P < .046) more than in Lite interventions (P = .11), and diastolic blood pressure improved in both Full (P = .02) and Lite (P = .03) interventions. Annual renewal of the school and volunteer commitment needed to maintain KiPOW! was found to be sustainable. KiPOW! is a generalizable academic-community partnership promoting face-to-face contact between students and trusted health mentors to reinforce school wellness policies and foster youth confidence in decision-making about nutrition- and activity-related behaviors to achieve reduced BMI percentile and lowered blood pressure.


Alpha enhancement: a comparison study of biofeedback, open focus training, and control procedures.
Alpha wave production has been related to affective and physiological arousal states since Berger's (1929) initial research. More recently, the possibility of subjects' control of alpha production has been investigated via the innovation of biofeedback procedures. Research conducted by Kamiya in the 1960s and others led to the early conclusion that alpha-wave production could be controlled and that such control could facilitate enhancement of a person's state of physical and psychological well-being. Subsequent research data have questioned these conclusions. The present study focused upon alpha-wave production with or without a procedure for relaxation called "open-focus training." Twenty subjects were divided into four equal groups and seen for three 20-min. sessions. Results suggested a deterioration of alpha production with all groups combined, no significant differences between the biofeedback and no biofeedback control groups (without "open-focus training"), and greater decrease in alpha production during each session in the "open-focus" groups (with or without biofeedback). These unusual results and their implications are discussed.


Parental smoking behavior and caries experience in preschool children.
The study aimed to explore the association between parental smoking behavior and caries experience in young children, taking into account the socioeconomic status and oral health-related behavior. Cross-sectional data from 1250 3-year-old and 1283 5-year-old children from four geographical areas in Flanders (Belgium) were analyzed. Children were examined at school by trained dentist-examiners, using standard criteria and calibrated examination methodology. Data on oral hygiene and dietary habits, oral health behavior, sociodemographic variables, and parental smoking behavior were obtained through structured questionnaires, completed by the parents. Visible caries experience (i.e. d(3)mft > 0) was seen in 7% of 3-year olds and 31% of 5-year olds. In both age groups, 30% of the parents reported smoking behavior. Univariable logistic regression analysis with caries prevalence as the dependent variable, revealed that parental smoking was a significant independent variable. After controlling for age, gender, sociodemographic characteristics, oral hygiene, and dietary habits, the effect of family smoking status was no longer significant in 3-year-old children (OR = 1.98; 95% CI: 0.68-5.76). In 5-year olds the significant relationship between parental smoking behavior and caries experience persisted after adjusting for the other evaluated variables (OR = 3.36; 95% CI: 1.49-7.58). The results of this study illustrate the existence of a significant association between parental smoking behavior and caries experience in 5-year-old children.


Marginal and internal adaptation of composite restorations using a resin liner on deproteinized substrate.
The purpose of this study was to evaluate the use of resin liner on deproteinized substrate on marginal and internal adaptation of composite restorations. Twenty-four recently extracted 3rd molars were selected. The crowns were sectioned in a mesio-distal direction, and the specimens were ground to expose a flat enamel area of at least 6 mm in diameter. Cavities were prepared on the central area of flattened surfaces. The specimens were randomly assigned into four groups (n = 12): SB - 1. Acid etch, 2. Single bond application (SB); NaOCl/SB - 1. acid etch, 2. 10% sodium hypochlorite solution application for 60 s (NaOCl), 3. SB; SB/PL - 1. acid etch, 2. SB, 3. protect liner F (PL); NaOCl/SB/PL - 1. acid etch, 2. NaOCl, 3. SB, 4. PL. All cavities were restored with Filtek Z250 and polished. The outer and internal margins were stained using Caries Detector (Kuraray), observed under the stereomicroscope, and transferred to a computer measurement program. The length of the gap was expressed as a percentage of the total length of the margins observed. Data (internal adaptation) were submitted to ANOVA and Tukey's test. There were no gaps at enamel outer margins in any specimen of any group. There was no statistically significant difference in internal adaptation between SB (18%) and NaOCl/SB (18%). NaOCl/SB/PL showed the worst internal adaptation (21%), with the higher percentage of internal gaps, statistically differing from SB/PL, which showed the best internal adaptation (12%). Resin liner can effectively enhance internal adaptation on demineralized dentin. However, on demineralized and deproteinized dentin it affects the internal adaptation of composite restorations negatively.


Emerging SARS-CoV-2 variants of concern potentially expand host range to chickens: insights from AXL, NRP1 and ACE2 receptors.
The possibilities of cross-species transmission of SARS-CoV-2 variants of concern (VOCs) between humans and poultry species are unknown. The analysis of the structure of receptor was used to investigate the potential of emerging SARS-CoV-2 VOCs to expand species tropism to chickens based on the interaction between Spike (S) protein and tyrosine kinase receptor UFO (AXL), angiotensin-converting enzyme 2 (ACE2), and neuropilin 1 (NRP1) with substantial public health importance. The structural and genetic alignment and surface potential analysis of the amino acid (aa) in ACE2, AXL, and NRP1 in human, hamster, mouse, mink, ferret, rhesus monkey and chickens were performed by Swiss-Model and pymol software. The critical aa sites that determined the susceptibility of the SARS-CoV-2 to the host were screened by aligning the residues interfacing with the N-terminal domain (NTD) or receptor-binding domain (RBD) of Spike protein. The binding modes of chickens AXL and ACE2 to S protein are similar to that of the ferret. The spatial structure and electrostatic surface potential of NRP1 showed that SARS-CoV-2 VOCs could not invade chickens through NRP1 easily. These results suggested that emerging SARS-CoV-2 VOCs potentially expand the host range to chickens mainly through ACE2 and AXL receptors, while NRP1 receptor may rarely participate in the future epidemic of coronavirus disease 2019 in chickens.


Effects of acute and subchronic AT1 receptor blockade on cardiovascular, hydromineral and neuroendocrine responses in female rats.
Female Wistar rats were ovariectomized (OVX) and separated into two groups that received either estradiol cypionate (EC, 40 μg/kg, sc; OVX-EC) or vehicle (corn oil, sc; OVX-oil) for 14 consecutive days. On the 7th day of treatment, a subset of animals from both the OVX-oil and OVX-EC groups was subjected to subchronic losartan (AT1 receptor antagonist) treatment (0.1g/L in drinking water; ~15 mg/kg/day) for 7 days. Other group of OVX-oil and OVX-EC rats was submitted to an acute losartan injection (100mg/kg, ip) on the 14th day of hormone replacement. In both protocols, the following parameters were measured: I) mean arterial pressure (MAP) and heart rate (HR); II) water and 0.3M saline intake; III) angiotensin II (ANG II), atrial natriuretic peptide (ANP), vasopressin (AVP) and oxytocin (OT) plasma concentrations; and IV) urinary and plasma sodium concentrations. Acute AT1 blockade induced a significant reduction in the MAP in the OVX rats, resulting in increased HR and water intake, which were attenuated by estradiol therapy. Acute AT1 blockade also increased ANG II and OT and reduced ANP plasma concentrations, with no changes in AVP secretion. In addition, acute hypotension was accompanied by a decrease in natriuresis, which was unaltered by estradiol. Subchronic AT1 blockade induced a significant decrease in MAP without changing HR in both groups. Additionally, subchronic losartan treatment induced sodium appetite in OVX rats. Prolonged AT1 blockade increased ANG II and AVP and reduced ANP plasma concentrations. Moreover, it increased natriuresis but did not alter plasma OT concentrations. Finally, estradiol treatment attenuated the increase in salt intake and plasma ANG II concentrations induced by subchronic AT1 blockade. In conclusion, our results suggest differential adaptive responses to the acute or subchronic losartan treatment in OVX and OVX-EC rats.


Effect of glycerol on glucokinase activity: loss of cooperative behavior with respect to glucose.
Glucose phosphorylation catalyzed by rat liver glucokinase measured at saturating concentrations of MgATP2- shows a cooperative response with respect to glucose in the concentration range 0.25-5 mM with a Hill coefficient of 1.6. In this range of glucose concentrations, the degree of cooperativity was dependent on the presence of glycerol in the assay mixture, and it decreased progressively and disappeared completely as the glycerol concentration reached about 20% (v/v) glycerol. If attention was confined to concentrations above 5 mM, no cooperativity could be detected either in the absence or in the presence of glycerol. The limiting velocity of the glucokinase reaction (measured at saturating concentrations of glucose and MgATP2-), and the half-saturation concentration for glucose and MgATP2- were all decreased by about 50-60% as the glycerol concentration was raised from zero to 30% (v/v). The presence of glycerol had no effect on the qualitative inhibition patterns of MgADP2-, glucose 6-phosphate, or N-acetylglucosamine, and only slight effects on the quantitative half-saturation values and inhibition constants. All of these effects caused by glycerol were fully reversible by decreasing the concentration of glycerol by dilution. Simulation studies based on the "mnemonical" model of glucokinase action proposed earlier [A. C. Storer and A. Cornish-Bowden (1977) Biochem. J. 165, 61-69] show that the effects of glycerol on glucokinase-catalyzed glucose phosphorylation can simply be explained assuming the glycerol favors the existence of the conformation of the enzyme with a higher affinity for glucose and thus supports the model.


Autophagy is increased in mice after traumatic brain injury and is detectable in human brain after trauma and critical illness.
Autophagy is a homeostatic process for recycling of proteins and organelles, that increases during times of nutrient deprivation and is regulated by reactive oxygen species. We reported that autophagy can also be induced after traumatic brain injury (TBI) in mice.1 Specifically, autophagosomes and multilamellar bodies were frequently observed in cell processes and axons in injured brain regions by electron microscopy, and lipidated microtubule-associated protein light chain 3 (LC3-II), was increased after TBI vs. controls. To determine if antioxidants could reduce autophagy, separate mice were treated with the antioxidant ?-glutamylcysteinyl ethyl ester (GCEE). Treatment with GCEE preserved total antioxidant reserves, reduced LC3-II in injured brains, and improved both behavioral and histological outcome after TBI. Here we report that LC3-II and autophagosomes were detectable in brain tissue from humans after TBI. Taken together, we show that autophagy occurs after both experimental and clinical TBI, and that oxidative stress contributes to overall neuropathology after TBI in mice, at least in part by initiating or influencing autophagy.


The prey of web-building spiders compared with feeding experiments (Araneae: Araneidae, Linyphiidae, pholcidae, Agelenidae).
Feeding experiments with 2,520 prey animals show differences in consumption rate and palatability for four spider species (Zygiella x-notata, Linyphia triangularis, Tegenaria atrica, Pholcus phalangioides). A possible protection against predators by chemical defence is discussed with special regard to 30 species of Heteroptera. Chemical weapons possess an astonishingly low deterrent effect whereas thick chitinisation (Coleoptera) is found to give very effective protection. Studies of the actual prey of these webbuilding spiders gave similar results in Araneidae and Linyphiidae. Nematocera and Homoptera are the most important prey group. Hymenoptera, Coleoptera and Brachycera were seldom caught. In contrast to this, the prey of Tegenaria and Pholcus consists mainly of Brachycera, Coleoptera and Hymenoptera, whereas Nematocera and Homoptera are rarely caught. The prey animals are mostly of small size. Only Pholcus and Tegenaria catch larger specimens. An ecological classification of the prey of Linyphiidae and Araneidae shows high percentages of phytophagous and detritophagous insects. Compared to the potential prey (trap data), predators, parasites and pollinating insects are underrepresented in the actual prey.


Is there a place for gastroenterostomy in patients with advanced cancer of the head of the pancreas?
There remains doubt about the need for gastroenterostomy in patients with advanced cancer of the pancreatic head, performed either prophylactically or when passage of food becomes impossible. The records of 142 patients admitted for advanced pancreatic cancer to the Erasmus University Hospital over a period of 11 years were reviewed. We concentrated especially on the pre- and postoperative intake of food in cases involving gastroenterostomy and the morbidity and mortality associated with abdominal surgery in these patients. Of 129 patients without symptoms of gastric outlet obstruction at the time of diagnosis, 31 underwent prophylactic gastroenterostomy. The procedure did not prevent gastric outlet obstruction in 4 patients. Of the remaining 98 patients, 15 developed gastric outlet obstruction. Cox proportional hazards analysis showed no significant difference in the interval to the occurrence of a symptomatic obstruction between these two groups, taking into account other covariables. Postoperative complications and mortality regarding a gastroenterostomy were high, ranging from 9% to 41% and 11% to 33%, respectively. Our results do not indicate that prophylactic gastroenterostomy may significantly prevent future gastric outlet obstruction; therefore, as it also increases morbidity, it should not be performed. A gastroenterostomy to relieve symptoms should be considered carefully, as the success rate is low and is accompanied by a considerable incidence of morbidity and mortality.