Effects of maternal diabetes on fetal expression of insulin-like growth factor and insulin-like growth factor binding protein mRNAs in the rat.
Maternal diabetes is associated in humans and rats with an increased risk for fetal growth abnormalities and malformations. Therefore, the effect of maternal diabetes on expression of genes that regulate fetal growth and differentiation is of considerable interest. Developmental growth is regulated in part by the expression and availability of insulin-like growth factors (IGFs). Postnatal expression of a subset of the IGFs and IGF binding proteins (IGFBPs) has been demonstrated to be regulated in response to diabetes and other metabolic conditions. We used in situ hybridization to analyze the effect of maternal diabetes, induced by streptozotocin (STZ) prior to mating, upon prenatal rat IGF and IGFBP mRNA expression. At gestational day (GD) 14, the most striking effect of maternal diabetes on fetal IGF/IGFBP gene expression was a marked increase in the abundance of IGFBP-1 mRNA within the liver primordia of fetuses isolated from diabetic dams compared to age-matched controls. This upregulation cannot be entirely due to the approximately one-half-day delay in fetal development (based on limb bud staging) associated with maternal diabetes, as there was no gross difference in the level of IGFBP-1 mRNA between GD13 and GD14 control fetal livers. In contrast, the fetal mRNA expression patterns of IGF-I, IGF-II and IGFBP-2, -3, -4, -5 and -6 were not grossly altered by maternal diabetes. These data are consistent with the hypothesis that IGFBP-1 produced within the fetal liver and secreted into fetal circulation may play a role in regulating rat fetal growth.


Activation of the Rb/E2F1 pathway by the nonproliferative p38 MAPK during Fas (APO1/CD95)-mediated neuronal apoptosis.
Aberrant activation of the Rb/E2F1 pathway in cycling cells, in response to mitogenic or nonmitogenic stress signals, leads to apoptosis through hyperphosphorylation of Rb. To test whether in postmitotic neurons the Rb/E2F1 pathway can be activated by the nonmitogenic stress signaling, we examined the role of the p38 stress-activated protein kinase (SAPK) in regulating Rb phosphorylation in response to Fas (CD95/APO1)-mediated apoptosis of cultured cerebellar granule neurons (CGNs). Anti-Fas antibody induced a dramatic and early activation of p38. Activated p38 was correlated with the induction of hyperphosphorylation of both endogenous and exogenous Rb. The p38-selective inhibitor, SB203580, attenuated such an increase in pRb phosphorylation and significantly protected CGNs from Fas-induced apoptosis. The cyclin-dependent kinase-mediated Rb phosphorylation played a lesser role in this neuronal death paradigm, since cyclin-dependent kinase inhibitors, such as olomoucine, roscovitine, and flavopiridol, did not significantly prevent anti-Fas antibody-evoked neuronal apoptosis. Hyperphosphorylation of Rb by p38 SAPK resulted in the release of Rb-bound E2F1. Increased E2F1 modulated neuronal apoptosis, since E2F1-/- CGNs were significantly less susceptible to Fas-mediated apoptosis in comparison with the wild-type CGNs. Taken together, these studies demonstrate that neuronal Rb/E2F1 is modulated by the nonproliferative p38 SAPK in Fas-mediated neuronal apoptosis.


Reconstruction of the middle hepatic vein using a vein graft from the resected portion of the liver.
The middle hepatic veins are often infiltrated by intrahepatic cholangiocarcinoma. Reconstruction of the hepatic vein plays a critical role in preserving more of the residual liver volume and reducing the risk of postoperative liver failure in extreme hepatectomy. We here report a novel way to reconstruct middle hepatic vein by using vessel grafts from wasted liver. Case 1: A 64-year-old man was diagnosed with intrahepatic cholangiocarcinoma. The bifurcation and left branch of the portal vein were stenosed, and the root of the middle hepatic vein was infiltrated by the tumor. An extended left hepatectomy was performed, the portal vein was resected and reconstructed, and the middle hepatic vein was reconstructed by anastomosing the proximal left hepatic vein to the distal middle hepatic vein. Case 2: A 69-year-old woman was diagnosed with intrahepatic cholangiocarcinoma. The tumor was located in the left lobe of the liver and the left and middle hepatic veins were infiltrated by the tumor. An extended left hepatectomy was performed, and the left portal vein was used as a vein graft to reconstruct the middle hepatic vein. Both of the two patients' postoperative ultrasound showed vessel graft patency. Using a vein graft from the resected portion of the liver to reconstruct the middle hepatic vein was a useful technique and showed good result.


A rapid and simple assay for human blood malignancy engraftment, homing and chemotherapy treatment using fluorescent imaging of avian embryos.
Detection of grafted human cells in mice using fluorescence is a rapid and simple technique whose use is continually expanding. Robust engraftment of human hematological malignancy (HHM) lines and patient cells into the naturally immunodeficient turkey embryo has recently been demonstrated by polymerase chain reaction (PCR), fluorescence activated cell sorting (FACS) and histology. We demonstrate here that fluorescence imaging is a rapid and simple technique for detecting engraftment and homing of cells derived from HHM in turkey embryos. Raji lymphoma cells expressing a far-red fluorescent protein were injected intravascularly into turkey embryos and fluorescence was detected 8 days later in their limbs and skulls. Much stronger signals were obtained after removal of the bones from the limbs. Unlabeled Raji cells did not give a fluorescent signal. Treatment with doxorubicin dramatically reduced the fluorescent signal. Intravenously injected HL-60 leukemia cells labeled with infrared-fluorescing dye were detected in the bone marrow after 16 h. Homing was active, although some non-specific fluorescence was present. Use of fluorescence imaging of HHM in turkey embryos is therefore feasible and reduces the time, effort and expense for detecting engraftment. This technique has potential to become a high-throughput xenograft system for hematological chemotherapy development and testing, and for study of hematological cell homing.


Drug overdose with refractory bradycardia and hypotension.
In the emergency department physicians are often called upon to make decisions with limited information. Often the correct diagnosis and treatment hinge on one piece of information, which may be the key to the entire presentation. We present a case report of a patient who presented with refractory bradycardia and hypotension who had over-dosed on calcium channel blockers as well as beta blockers. The underlying cause however was myxedema. Were it not for the presence of hypothermia, the correct diagnosis of myxedema secondary to severe hypothyroidism could have been missed. We also briefly review the pathophysiology and treatment of myxedema. We present a case of refractory bradycardia and hypotension in a patient who had overdosed on calcium channel blockers as well as beta blockers. Paying close attention to all the details of the case eventually uncovered the underlying severe hypothyroidism and myxedema. In the emergency department we are always called upon to make decisions with limited information. It is also paying close attention to all of the information presented that allows one to not miss any key pieces central to the final diagnosis.


Connexin hemichannels with prostaglandin release in anabolic function of bone to mechanical loading.
Mechanical stimulation, such as physical exercise, is essential for bone formation and health. Here, we demonstrate the critical role of osteocytic Cx43 hemichannels in anabolic function of bone in response to mechanical loading. Two transgenic mouse models, R76W and Δ130-136, expressing dominant-negative Cx43 mutants in osteocytes were adopted. Mechanical loading of tibial bone increased cortical bone mass and mechanical properties in wild-type and gap junction-impaired R76W mice through increased PGE2, endosteal osteoblast activity, and decreased sclerostin. These anabolic responses were impeded in gap junction/hemichannel-impaired Δ130-136 mice and accompanied by increased endosteal osteoclast activity. Specific inhibition of Cx43 hemichannels by Cx43(M1) antibody suppressed PGE2 secretion and impeded loading-induced endosteal osteoblast activity, bone formation and anabolic gene expression. PGE2 administration rescued the osteogenic response to mechanical loading impeded by impaired hemichannels. Together, osteocytic Cx43 hemichannels could be a potential new therapeutic target for treating bone loss and osteoporosis.


Biphenyl- and phenylnaphthalenyl-substituted 1H-imidazole-4,5-dicarbonitrile catalysts for the coupling reaction of nucleoside methyl phosphonamidites.
Crystal structures are reported for three substituted 1H-imidazole-4,5-dicarbonitrile compounds used as catalysts for the coupling reaction of nucleoside methyl phosphonamidites, namely 2-(3',5'-dimethylbiphenyl-2-yl)-1H-imidazole-4,5-dicarbonitrile, C19H14N4, (I), 2-(2',4',6'-trimethylbiphenyl-2-yl)-1H-imidazole-4,5-dicarbonitrile, C20H16N4, (II), and 2-[8-(3,5-dimethylphenyl)naphthalen-1-yl]-1H-imidazole-4,5-dicarbonitrile, C23H16N4, (III). The asymmetric unit of (I) contains two independent molecules with similar conformations. There is steric repulsion between the imidazole group and the terminal phenyl group in all three compounds, resulting in the nonplanarity of the molecules. The naphthalene group of (III) shows significant deviation from planarity. The C-N bond lengths in the imidazole rings range from 1.325 (2) to 1.377 (2) Å. The molecules are connected into zigzag chains by intermolecular N-H···N(imidazole) [for (I)] or N-H····N(cyano) [for (II) and (III)] hydrogen bonds.


Liver disease from surreptitious administration of urethane.
We report subacute necrosis, peliosis hepatis, venoocclusive disease and hepatic angiosarcoma after long-term administration of urethane. We take this to be the 12th case of urethane-induced hepatitis and the first associated with vascular liver tumor.


Changes in tissue inflammation, angiogenesis and apoptosis in endometriosis, adenomyosis and uterine myoma after GnRH agonist therapy.
Information is limited regarding the multifunctional role of GnRH agonist (GnRHa) therapy in reproductive diseases. We investigated the pattern of changes in inflammatory reaction, micro-vessel density and apoptosis in the tissues collected from women with endometriosis, adenomyosis and uterine myoma who were treated with or without GnRHa therapy. Biopsy specimens were collected from lesions, myometria and corresponding endometria of 45 women with ovarian endometrioma, 35 women with adenomyosis and 56 women with uterine myoma. A fraction of these women were treated with GnRHa therapy for a variable period of 3-6 months before surgery. We performed immunohistochemical analysis of CD68, a macrophage (Mvarphi) marker and von Willebrand factor (VWF), a vessel marker, using respective antibodies. Changes in apoptosis were examined using TdT-mediated dUTP-biotin nick end-labeling assay and by the immunoexpression of activated caspase-3 in tissues after GnRHa therapy. The infiltration of CD68-positive Mvarphi and VWF-positive micro-vessel density were significantly decreased in the endometria of women with endometriosis, adenomyosis and uterine myoma in the GnRHa-treated group when compared with that in the non-treated group. Marked decreases in inflammatory and angiogenic responses were observed in lesions and myometria of these diseases. When compared with the non-treated group, a significant increase in apoptotic index (apoptotic cells per 10 mm(2) area) and quantitative-histogram scores of activated caspase-3 after GnRHa therapy were observed in the eutopic endometria, lesions and myometria of these diseases. GnRHa was able to markedly reduce the inflammatory reaction and angiogenesis and to significantly induce apoptosis in tissues derived from women with endometriosis, adenomyosis and uterine myoma. These multiple biological effects at the tissue level may be involved in the regression of these reproductive diseases.


Hematopoietic differentiation is characterized by a transient peak of entropy at a single-cell level.
Mature blood cells arise from hematopoietic stem cells in the bone marrow by a process of differentiation along one of several different lineage trajectories. This is often represented as a series of discrete steps of increasing progenitor cell commitment to a given lineage, but as for differentiation in general, whether the process is instructive or stochastic remains controversial. Here, we examine this question by analyzing single-cell transcriptomic data from human bone marrow cells, assessing cell-to-cell variability along the trajectories of hematopoietic differentiation into four different types of mature blood cells. The instructive model predicts that cells will be following the same sequence of instructions and that there will be minimal variability of gene expression between them throughout the process, while the stochastic model predicts a role for cell-to-cell variability when lineage commitments are being made. Applying Shannon entropy to measure cell-to-cell variability among human hematopoietic bone marrow cells at the same stage of differentiation, we observed a transient peak of gene expression variability occurring at characteristic points in all hematopoietic differentiation pathways. Strikingly, the genes whose cell-to-cell variation of expression fluctuated the most over the course of a given differentiation trajectory are pathway-specific genes, whereas genes which showed the greatest variation of mean expression are common to all pathways. Finally, we showed that the level of cell-to-cell variation is increased in the most immature compartment of hematopoiesis in myelodysplastic syndromes. These data suggest that human hematopoietic differentiation could be better conceptualized as a dynamical stochastic process with a transient stage of cellular indetermination, and strongly support the stochastic view of differentiation. They also highlight the need to consider the role of stochastic gene expression in complex physiological processes and pathologies such as cancers, paving the way for possible noise-based therapies through epigenetic regulation.


The value of combining individual and small area sociodemographic data for assessing and handling selective participation in cohort studies: Evidence from the Swedish CardioPulmonary bioImage Study.
To study the value of combining individual- and neighborhood-level sociodemographic data to predict study participation and assess the effects of baseline selection on the distribution of metabolic risk factors and lifestyle factors in the Swedish CardioPulmonary bioImage Study (SCAPIS). We linked sociodemographic register data to SCAPIS participants (n = 30,154, ages: 50-64 years) and a random sample of the study's target population (n = 59,909). We assessed the classification ability of participation models based on individual-level data, neighborhood-level data, and combinations of both. Standardized mean differences (SMD) were used to examine how reweighting the sample to match the population affected the averages of 32 cardiopulmonary risk factors at baseline. Absolute SMDs >0.10 were considered meaningful. Combining both individual-level and neighborhood-level data gave rise to a model with better classification ability (AUC: 71.3%) than models with only individual-level (AUC: 66.9%) or neighborhood-level data (AUC: 65.5%). We observed a greater change in the distribution of risk factors when we reweighted the participants using both individual and area data. The only meaningful change was related to the (self-reported) frequency of alcohol consumption, which appears to be higher in the SCAPIS sample than in the population. The remaining risk factors did not change meaningfully. Both individual- and neighborhood-level characteristics are informative in assessing study selection effects. Future analyses of cardiopulmonary outcomes in the SCAPIS cohort can benefit from our study, though the average impact of selection on risk factor distributions at baseline appears small.


The use of fetal bovine collagen on chronic wounds increases limb salvage: a single-center retrospective analysis.
As part of a quality assurance project at a large tertiary care surgical program in New York City, the effect of debridement, negative pressure wound therapy, and cellular- and tissue-based products (CTPs) on limb salvage was evaluated based on the following outcomes: freedom from amputation, wound closure, and freedom from readmission. Fetal bovine collagen was among the CTPs evaluated. The data used in this study were derived from a database of all patients who had undergone procedures involving placement of a dermal matrix at the center over a 2.5-year period (January 2016-June 2018). This retrospective analysis included 256 patients who underwent debridement and/or placement of a CTP as part of the treatment course for chronic wounds. Of the 252 patients identified, 34 required either minor or major all-cause amputation from the initial wound intervention, whereas for 218 patients, there were no recorded amputations through the end of the study period after the initial wound intervention. When fetal bovine collagen was evaluated as an explanatory variable to the presence of future amputation, a statistically significant relationship between the variables was found. The results of the current data analysis indicate that a treatment algorithm that includes appropriate antibiotic therapy, tangential hydrosurgery, application of fetal bovine collagen, and a short course of negative pressure wound therapy may be a more favorable option to achieve limb salvage, freedom from readmission, and wound closure.


Effects of cigarette smoking on lung function of Saudi students.
This study was carried out to investigate the association between cigarette smoking and state of lung function among Saudi male students. A cross sectional study was conducted on a group of 680 male Saudi students. Detailed personal questionnaire, British Medical Research Council questionnaire on respiratory symptoms and smoking habit, were administered and forced spirometry and anthropometric measurements were conducted on them. Multiple regression models were used to study the cumulative effect of smoking on the function of the lung of smoking students. The percentage of cigarette smoking among the studied group was 20.29%. Smoking students had significantly lower values for lung function tests (FEV1%, FEF200-1200, FEF25-75, FEF75-85, and PEFR) compared to non-smokers. After controlling for other confounding variables, increased duration of smoking and number of cigarette smoked per day were significantly associated with more limitation of airflow in airways of the smoking young students. Recommendations were discussed accordingly.


Two cases of an intrascrotal cystic mass mimicking a testicular tumor and review of the literature.
A 39-year-old man had a 15-year history of an enlarging, firm, nontender mass on the right side of the scrotum after perineal trauma. Right high inguinal orchiectomy was performed, and the histopathological diagnosis was chronic hematocele. A 50-year-old man had a 2-year history of an enlarging, firm, nontender mass on the left side of the scrotum. Left high inguinal orchiectomy was performed. The histopathological diagnosis was a thick membranous hydrocele associated with chronic epididymitis. There were various clinical and histopathological similarities between the two cases. We discuss other intrascrotal cystic masses similar to our cases along with a review of the literature.


[Involutional entropion and ectropion].
Entropion and ectropion are very common among old people. These malpositions concern mostly the lower lids. Involutional entropion and ectropion have some pathophysiologic mechanisms in common: lower lid horizontal laxity and lid retractor detachment. However, orbicularis muscle hypertrophy occurs only in entropion, and excess of posterior lamella has to be considered in ectropion. Clinical examination will guide surgical treatment. The authors present the main surgical procedures according to clinical findings. The goal is to prevent recurrence.


Kalirin: a novel genetic risk factor for ischemic stroke.
Cerebrovascular and cardiovascular diseases are the leading causes of death and disability worldwide. They are complex disorders resulting from the interplay of genetic and environmental factors, and may share several susceptibility genes. Several recent studies have implicated variants of the Kalirin (KALRN) gene with susceptibility to cardiovascular and metabolic phenotypes, but no studies have yet been performed in stroke patients. KALRN is involved, among others, in the inhibition of inducible nitric oxide synthase, in the regulation of ischemic signal transduction, and in neuronal morphogenesis, plasticity, and stability. The goal of the present study was to determine whether SNPs in the KALRN region on 3q13, which includes the Ropporin gene (ROPN1), predispose to ischemic stroke (IS) in a cohort of Portuguese patients and controls. We genotyped 34 tagging SNPs in the KALRN and ROPN1 chromosomal region on 565 IS patients and 517 unrelated controls, and performed genotype imputation for 405 markers on chromosome 3. We tested the single-marker association of these SNPs with IS. One SNP (rs4499545) in the ROPN1-KALRN intergenic region and two SNPs in KALRN (rs17286604 and rs11712619) showed significant (P < 0.05) allelic and genotypic (unadjusted and adjusted for hypertension, diabetes, and ever smoking) association with IS risk. Thirty-two imputed SNPs also showed an association at P < 0.05, and actual genotyping of three of these polymorphisms (rs7620580, rs6438833, and rs11712039) validated their association. Furthermore, rs11712039 was associated with IS (0.001 < P < 0.01) in a recent well-powered genomewide association study (Ikram et al. 2009). These studies suggest that variants in the KALRN gene region constitute risk factors for stroke and that KALRN may represent a common risk factor for vascular diseases.


The Spontaneous Imbibition of Micro/Nano Structures in Tight Matrix and the Influence on Imbibition Potential.
Tight matrix has relatively low permeability and porosity, with abundant micro/nano pores. The capillary force in these pores are relatively strong, making the wetting liquid easier to be imbibed in the matrix. This process is called spontaneous imbibition. The complexity of pore structure is identified as one of the key factors influencing the imbibition process, but the detailed mechanism is not clear. Thus, in this work, a method is proposed to evaluate the influence of pore structure on imbibition process. Pore structure has fractal properties in a specific scale. By using the fractal theory, an imbibition model is provided to analyze the influence of microscopic structures on spontaneous imbibition, considering the pore size distribution and pore connectivity. Also, based on this model, the influencing factors on dimensionless imbibition and diffusion rate are discussed. Results show that the pore structure has more branches, larger and shorter sub-throats has higher chance to gain a high imbibition rate. Finally, a 3D imbibition parameter cube is constructed to determine the parameter combinations in favor of strong water diffusion potential. By utilizing the analysis method based on the fractal theory, we can effectively evaluate the imbibition potential. It is helpful to provide a guidance to evaluate the water imbibition to gas production.


Multiple Incidental Unruptured Splenic Artery Aneurysms Following Severe Trauma.
Splenic artery aneurysm is a relatively rare, potentially life-threatening condition due to its high potential for rupture. We report a case of two incidentally found unruptured splenic artery aneurysms in a 39 year-old female victim of severe trauma resulting from a motor vehicle accident (MVA). Management by coiling of the splenic artery aneurysm and embolization to the entire segment distal to it was successfully performed for this patient.


Endovascular embolization strategy for renal arteriovenous malformations.
Renal arteriovenous malformations (AVMs) are rare vascular malformations that cause hematuria. Treatment for renal AVMs has evolved from open nephrectomy to transcatheter arterial embolization (TAE). To retrospectively evaluate efficacy and adverse events of TAE for renal AVMs. We examined 12 patients (three men, nine women; mean age, 56 years) with renal AVM with gross hematuria, who underwent 14 sessions of treatment, using various embolization materials (liquid embolization agents, gelatin sponge, and coils). Among the 12 patients, 10 had cirsoid AVMs, eight of which were high-flow lesions. The remaining two patients had aneurismal AVMs. We assessed technical and clinical success, and also complications. All patients were followed for 7-92 months (mean, 48 months). Technical success was obtained in all patients. Primary clinical success was obtained in all patients; however, recurrence was observed in two patients who were treated with coils alone. A second session of TAE led to the sustained relief of symptoms. Clinical success rate was significant better (P = 0.045) when coils combined with other agents or liquid agents were used, than when only coils were used. No major complications occurred in any of patients; post-embolization syndrome and deterioration of renal function were not observed. TAE treatment was safe, effective, and provided a good outcome, except when only coils were used as the embolization agent.


Non-linear Memristive Synaptic Dynamics for Efficient Unsupervised Learning in Spiking Neural Networks.
Spiking neural networks (SNNs) are a computational tool in which the information is coded into spikes, as in some parts of the brain, differently from conventional neural networks (NNs) that compute over real-numbers. Therefore, SNNs can implement intelligent information extraction in real-time at the edge of data acquisition and correspond to a complementary solution to conventional NNs working for cloud-computing. Both NN classes face hardware constraints due to limited computing parallelism and separation of logic and memory. Emerging memory devices, like resistive switching memories, phase change memories, or memristive devices in general are strong candidates to remove these hurdles for NN applications. The well-established training procedures of conventional NNs helped in defining the desiderata for memristive device dynamics implementing synaptic units. The generally agreed requirements are a linear evolution of memristive conductance upon stimulation with train of identical pulses and a symmetric conductance change for conductance increase and decrease. Conversely, little work has been done to understand the main properties of memristive devices supporting efficient SNN operation. The reason lies in the lack of a background theory for their training. As a consequence, requirements for NNs have been taken as a reference to develop memristive devices for SNNs. In the present work, we show that, for efficient CMOS/memristive SNNs, the requirements for synaptic memristive dynamics are very different from the needs of a conventional NN. System-level simulations of a SNN trained to classify hand-written digit images through a spike timing dependent plasticity protocol are performed considering various linear and non-linear plausible synaptic memristive dynamics. We consider memristive dynamics bounded by artificial hard conductance values and limited by the natural dynamics evolution toward asymptotic values (soft-boundaries). We quantitatively analyze the impact of resolution and non-linearity properties of the synapses on the network training and classification performance. Finally, we demonstrate that the non-linear synapses with hard boundary values enable higher classification performance and realize the best trade-off between classification accuracy and required training time. With reference to the obtained results, we discuss how memristive devices with non-linear dynamics constitute a technologically convenient solution for the development of on-line SNN training.


Detection of soft x rays with NEA III-V photocathodes.
We describe the experimental energy response of a negative electron affinity (NEA) III-V photocathode to x rays with energies from approximately 0.8 to approximately 3 keV. Energy resolutions, E/DeltaE, from approximately 1 to approximately 3 are obtained, together with approximately 100% quantum efficiency. Theoretical calculations based on an electron diffusion model are shown to be in good agreement with the experimental results. The use of NEA III-V photocathodes as efficient soft x-ray detectors with good energy and spatial resolution is discussed for imaging applications in x-ray astronomy.


The influence of pregnancy on the recurrence of cutaneous malignant melanoma in women.
Objective. The aim of this study was to determine whether pregnancy increases the recurrence risk of cutaneous malignant melanoma (CMM) in women with a history of stage I CMM. Methods. The electronic medical databases of Medline and Embase were explored. All 1084 obtained articles were screened on title and abstract using predetermined inclusion and exclusion criteria. A critical appraisal of relevance and validity was conducted on the remaining full text available articles. Results. Two studies were selected. Both studies revealed no significant difference in disease-free survival between women with stage I CMM and the control population. Conclusion. Pregnancy does not increase the recurrence risk of CMM in women with a history of stage I CMM.


Nod1 and nod2 are expressed in human and murine renal tubular epithelial cells and participate in renal ischemia reperfusion injury.
Nucleotide-binding oligomerization domain (Nod) 1 and Nod2 are members of a family of intracellular innate sensors that participate in innate immune responses to pathogens and molecules released during the course of tissue injury, including injury induced by ischemia. Ischemic injury to the kidney is characterized by renal tubular epithelial apoptosis and inflammation. Among the best studied intracellular innate immune receptors known to contribute to apoptosis and inflammation are Nod1 and Nod2. Our study compared and contrasted the effects of renal ischemia in wild-type mice and mice deficient in Nod1, Nod2, Nod(1 x 2), and in their downstream signaling molecule receptor-interacting protein 2. We found that Nod1 and Nod2 were present in renal tubular epithelial cells in both mouse and human kidneys and that the absence of these receptors in mice resulted in protection from kidney ischemia reperfusion injury. Significant protection from kidney injury was seen with a deficiency of Nod2 and receptor-interacting protein 2, and the simultaneous deficiency of Nod1 and Nod2 provided even greater protection. We conclude that the intracellular sensors Nod1 and Nod2 play an important role in the pathogenesis of acute ischemic injury of the kidney, although possibly through different mechanisms.


Controlled trials of rG-CSF and CD11b-directed MAb during hyperoxia and E. coli pneumonia in rats.
We studied the effects of inhibiting and augmenting neutrophil function by using an immunocompetent rat model of infectious and hyperoxic lung injury. After intrabronchial Escherichia coli challenge at all fractional inspired O2 (FIO2) values studied (FIO2 = 0.21, 0.60, and 0.95) and after lethal O2 exposure alone (FIO2 = 0.90), lung injury, as measured by histological and physiological changes, was reduced by a CD11b/CD18-directed monoclonal antibody (MAb 1B6, P < 0.05 vs. controls) but was increased by recombinant granulocyte colony-stimulating factor (rG-CSF; P < 0.05 vs. control; MAb 1B6 vs. rG-CSF, P < 0.004). Pulmonary neutrophil counts were reduced by MAb 1B6 (P < 0.04) and increased by rG-CSF (P < 0.0004) compared with control animals. However, despite antibiotics, MAb 1B6 and rG-CSF both significantly increased the relative risk of death, independent of O2 concentration, during E. coli pneumonia (1.74 [symbol: see text] 1.20 and 2.39 [symbol: see text] 1.19, respectively, each P < 0.01). During lethal hyperoxia, MAb 1B6 increased the relative risk of death (1.76 [symbol: see text] 1.28, P < 0.16), whereas rG-CSF had no effect on survival (0.97 [symbol: see text] 1.28, P = 0.89). Thus inhibition of neutrophil function attenuated and enhancement worsened lung injury in response to infectious and hyperoxic challenges, supporting a pathophysiological role of the neutrophil in these processes. However, it is problematic that MAb 1B6 therapy, despite preventing lung damage, ultimately worsened host defenses and survival. Furthermore, rG-CSF also adversely affected survival during infectious lung injury, demonstrating the inherent risks of inhibiting or augmenting neutrophil function in an immunocompetent host during infection.


Free light-chain proteinuria and normal renal histopathology and function in 11 dogs exposed to Lleishmania infantum, Ehrlichia canis, and Bbabesia canis.
The purpose of this retrospective study was to investigate the relationship among proteinuria consisting of immunoglobulin free light chains (FLCs), renal histopathologic findings, and routine markers of renal function in 11 dogs exposed to Leishmania infantum (n = 8), Ehrlichia canis (n = 2), and Babesia canis (n = 1). FLC proteinuria was suspected based on identification of a 22- to 27-kDa band by sodium dodecyl sulfate-agarose gel electrophoresis (SDS-AGE) and later confirmed by immunofixation electrophoresis. SDS-AGE identified an isolated band of 22-27 kDa in 8 dogs, whereas the remaining 3 had a 22- to 27-kDa band and an additional band of 67-72 kDa. The median urine protein-to-urine creatinine ratio was 0.37 (range, 0.11-2.24) and increased ratios were found in 6 dogs (54.5%) (reference value, <0.7). All dogs underwent histologic examination of renal percutaneous biopsy specimens and determination of serum creatinine and urea concentrations. Tissue samples for light microscopy were stained with hematoxylin-eosin, periodic acid-Schiff, Goldners trichrome, and methenamine silver. In the study group, the glomerular tufts, mesangium, tubulointerstitium, and vessels appeared unaffected. The median serum creatinine concentration in these 11 dogs was 1.3 mg/dL (range, 0.8-1.5 mg/dL; reference range, 0.6-1.5 mg/dL), whereas the concentration for urea was 28 mg/dL (range, 22-52 mg/dL; reference range, 20-50 mg/dL). All dogs had normal renal morphology and had normal serum creatinine and urea concentrations, suggesting that immunoglobulin FLC may be detected in the urine of dogs exposed to L. infantum, E. canis, and B. canis without any apparent structural or functional renal derangement.


Circadian Rhythms in Fractal Features of EEG Signals.
Time-of-day modulations affect both performance on a wide range of cognitive tasks and electrical activity of the brain, as recorded by electroencephalography (EEG). The aim of this work was to identify fluctuations of fractal properties of EEG time series due to circadian rhythms. In twenty-one healthy volunteers (all males, age between 20 and 30 years, chronotype: neutral type) high density EEG recordings at rest in open and closed eyes conditions were acquired in 4 times of the day (8.00 a.m., 11.30 a.m., 2.30 p.m., 7.00 p.m.). A vigilance task (Psychomotor Vigilance Test, PVT) was also performed. Detrended fluctuation Analysis (DFA) of envelope of alpha, beta and theta rhythms was performed, as well as Highuchi fractal dimension (HFD) of the whole band EEG. Our results evidenced circadian fluctuations of fractal features of EEG at rest in both eyes closed and eyes open conditions. Lower values of DFA exponent were found in the time T1 in closed eyes condition, likely effect of the sleep inertia. An alpha DFA exponent reduction was found also in central sensory-motor areas at time T3, the day time in which the sleepiness can be present. In eyes open condition, HFD lowered during the day. In eyes closed condition, an HFD increase was observed in central and frontal regions at time T2, the time in which alertness reaches its maximum and homeostatic sleep pressure is low. Complexity and the persistence of temporal correlations of brain rhythms change during daytime, parallel to changes in alertness and performance.


[Dissociation of testis and epididymis in incomplete descent].
Failure of fusion between testis and epididymis will usually be encountered during operations for undescended testis in children and for infertility in adults. In 325 groin dissections for undescended testis monorchism was diagnosed in 3.7% and nonfusion of testis and epididymis in 1.2%. Case reports of three unilateral and one bilateral conditions are presented. Intraoperative misjudgement of this condition is likely to occur if the blind ending epididymis is mistaken for an atrophic testis. Careful search for the missing testis is mandatory.


Inverting dynamic force microscopy: from signals to time-resolved interaction forces.
Transient forces between nanoscale objects on surfaces govern friction, viscous flow, and plastic deformation, occur during manipulation of matter, or mediate the local wetting behavior of thin films. To resolve transient forces on the (sub) microsecond time and nanometer length scale, dynamic atomic force microscopy (AFM) offers largely unexploited potential. Full spectral analysis of the AFM signal completes dynamic AFM. Inverting the signal formation process, we measure the time course of the force effective at the sensing tip. This approach yields rich insight into processes at the tip and dispenses with a priori assumptions about the interaction, as it relies solely on measured data. Force measurements on silicon under ambient conditions demonstrate the distinct signature of the interaction and reveal that peak forces exceeding 200 nN are applied to the sample in a typical imaging situation. These forces are 2 orders of magnitude higher than those in covalent bonds.


Use of an alternative light source to assess strangulation victims.
Alternative light sources (ALSs) are commonly used at crime scenes and in forensic laboratories to collect evidence such as latent fingerprints, body fluids, hair, and fibers. This article describes the use of this technology to reveal soft tissue injuries that are not visible to the naked or unaided eye in patients who report strangulation. The value of this information to the medical, nursing, and judicial systems is discussed. The records of the 172 strangulation patients seen in our forensic nurse examiner program between 2009 and 2010 were reviewed. The SPEX Crimescope (SPEX Forensics, Edison, New Jersey) was used during the assessment of all of them. Ninety-three percent of the patients had no visible evidence of external injuries on physical examination. The ALS revealed positive findings of intradermal injuries in 98% of that group. Information obtained with ALS devices helps medical and nursing practitioners understand the gravity of patients' injuries, influences medical treatment decisions and follow-up care, and supports the prosecution of the perpetrators of crimes of violence. Educational programs about the application of ALS and the interpretation of its findings are valuable for medical, nursing, and other forensic disciplines.


Age and equity in liver transplantation: An organ allocation model.
A moral liver allocation policy must be fair. We considered a 2-step, 2-principle allocation system called "age mapping." Its first principle, equal opportunity, ensures that candidates of all ages have an equal chance of getting an organ. Its second principle, prudential lifespan equity, allocates younger donor grafts to younger candidates and older donors to older candidates in order to increase the likelihood that all recipients achieve a "full lifespan." Data from 2476 candidates and 1371 consecutive adult liver transplantations (from 1999 to 2012) were used to determine whether age mapping can reduce the gap in years of life lost (YLL) between younger and older recipients. A parametric Weibull prognostic model was developed to estimate total life expectancy after transplantation using survival of the general population matched by sex and age as a reference. Life expectancy from birth was calculated by adding age at transplant and total life expectancy after transplantation. In multivariate analysis, recipient age, hepatitis C virus status, Model for End-Stage Liver Disease score at transplant of >30, and donor age were significantly related to prognosis after surgery (P < 0.05). The mean (and standard deviation) number of years of life from birth, calculated from the current allocation model, for various age groups were: recipients 18-47 years (n = 340) = 65.2 (3.3); 48-55 years (n = 387) = 72.7 (2.1); 56-61 years (n = 372) = 74.7 (1.7) and for recipients >61 years (n = 272) = 77.4 (1.4). The total number of YLL equaled 523 years. Redistributing liver grafts, using an age mapping algorithm, reduces the lifespan gap between younger and older candidates by 33% (from 12.3% to 8.3%) and achieves a 14% overall reduction of YLL (73 years) compared to baseline liver distribution. In conclusion, deliberately incorporating age into an allocation algorithm promotes fairness and increases efficiency.


Merits and limitations of continuous blood volume monitoring during haemodialysis. Summary of the EDTNA/ERCA Journal Club discussion: Winter 2005.
The discussion explored and expanded on the issues raised by Dasselaar et al in their review of the measurement of relative blood volume (RBV) changes during dialysis (NDT 2005). Dialysis machines incorporating blood volume monitoring and control are widely available in Europe. The use of continuous blood volume monitoring (CBVM) to help establish dry weight; problems with CBVM due to connection and use of single needle dialysis; the physiological processes that cause RBV changes during eating, exercise and posture changes; and the application of blood volume based biofeedback control were discussed by participants from ten countries. The 'take-home' messages from the discussion were that CBVM can assist in setting target weight, but must be used together with traditional measures and experience. Biofeedback control may help to achieve symptom-free dialysis, but staff should be prepared to monitor patients systematically for several weeks to obtain individualised settings. Users of CBVM should be aware of factors that can alter the central haematocrit leading to apparent changes in RBV. Practical guidelines should be developed to help staff interpret CBVM data effectively.


U2 small nuclear RNA 3' end formation is directed by a critical internal structure distinct from the processing site.
Mature U2 small nuclear RNA is generated by the removal of 11 to 12 nucleotides from the 3' end of the primary transcript. This pre-U2 RNA processing reaction takes place in the cytoplasm. In this study, the sequences and/or structures of pre-U2 RNA that are important for 3' processing have been examined in an in vitro system. The 7-methylguanosine cap, stem-loops I and II, the lariat branch site recognition sequence, the conserved Sm domain, and several other regions throughout the 5' end of U2 RNA have no apparent role in the 3' processing reaction. In fact, deletion of the entire first 104 nucleotides resulted in mini-pre-U2 RNAs which were efficiently processed. Similarly, deletion of the top two-thirds of stem-loop III or mutation of nucleotides in the loop of stem-loop IV had little effect on 3' processing. Most surprisingly, the precursor's 11- to 12-nucleotide 3' extension itself was of relatively little importance, since this sequence could be replaced with completely different sequences with only a minor effect on the 3' processing reaction. In contrast, we have defined a critical structure consisting of the bottom of stem III and the stem of stem-loop IV that is essential for 3' processing of pre-U2 RNA. Compensatory mutations which restore base pairing in this region resulted in normal 3' processing. Thus, although the U2 RNA processing activity recognizes the bottom of stem III and stem IV, the sequence of this critical region is much less important than its structure. These results, together with the surprising observation that the reaction is relatively indifferent to the sequence of the 11- to 12-nucleotide 3' extension itself, point to a 3' processing reaction of pre-U2 RNA that has sequence and structure requirements significantly different from those previously identified for pre-mRNA 3' processing.


Inhibition of ethylene biosynthesis by aminoethoxyvinylglycine and by polyamines shunts label from 3,4-[C]methionine into spermidine in aged orange peel discs.
The flux of radioactivity from 3,4-[(14)C]methionine into S-adenosyl-l-methionine (SAM), 1-aminocyclopropane-1-carboxylic acid (ACC), spermine, and spermidine while inhibiting conversion of ACC to ethylene by 100 millimolar phosphate and 2 millimolar Co(2+) was studied in aged peel discs of orange (Citrus sinensis L. Osbeck) fruit. Inhibition up to 80% of ethylene production by phosphate and cobalt was accompanied by a 3.3 times increase of label in ACC while the radioactivity in SAM was only slightly reduced. Aminoethoxyvinylglycine (AVG) increased the label in SAM by 61% and reduced it in ACC by 47%. Different combinations of standard solution, in which putrescine or spermidine were administered alone or with AVG, demonstrated clearly that inhibition of ethylene biosynthesis-at the conversion of SAM to ACC-by AVG, exogenous putrescine or exogenous spermidine, stimulated the incorporation of 3,4-[(14)C]methionine into spermidine.


Association of the alpha-adducin polymorphism with blood pressure and risk of myocardial infarction.
Genetic variation in adducin, a protein associated with the inner leaflet of the plasma membrane, may be in part responsible for salt-sensitive hypertension. In the Netherlands, 560 men who survived a myocardial infarction and 646 men who had undergone an orthopaedic intervention participated in a case-control study. In men in this study, the alpha-adducin polymorphism was not associated with the risk of myocardial infarction either among those with or among those without a clinical history of hypertension. In a cross-sectional analysis of blood pressure data from the controls, the alpha-adducin polymorphism was associated neither with self-reported hypertension (OR = 0.78, 95% CI = 0.51-1.19) nor with mean levels of systolic or diastolic blood pressure. Additional studies in other populations are needed to assess the contribution of alpha-adducin to high blood pressure and cardiovascular risk.


Efficiency of nodule initiation in cowpea and soybean.
When serial dilutions of a suspension of Bradyrhizobium japonicum strain 138 were inoculated onto both soybean and cowpea roots, the formation of nodules in the initially susceptible region of the roots of both hosts was found to be linearly dependent on the log of the inoculum dosage until an optimum dosage was reached. Approximately 30- to 100-fold higher dosages were required to elicit half-maximal nodulation on cowpea than on soybean in the initially susceptible zone of the root. However, at optimal dosages, about six times as many nodules formed in this region on cowpea roots than on soybean roots. There was no appreciable difference in the apparent rate of nodule initiation on these two hosts nor in the number of inoculum bacteria in contact with the root. These results are consistent with the possibility that cowpea roots have a substantially higher threshold of response to symbiotic signals from the bacteria than do soybean roots. Storage of B. japonicum cells in distilled water for several weeks did not affect their viability or efficiency of nodule initiation on soybean. However, the nodulation efficiency of these same cells on cowpea diminished markedly over a 2 week period. These differential effects of water storage indicate that at least some aspects of signal production by the bacteria during nodule initiation are different on the two hosts. Mutants of B. japonicum 138 defective in synthesis of soybean lectin binding polysaccharide were defective in their efficiency of nodule initiation on soybean but not on cowpea. These results also suggest that B. japonicum may produce different substances to initiate nodules on these two hosts.


Amelogenin, a major structural protein in mineralizing enamel, is also expressed in soft tissues: brain and cells of the hematopoietic system.
The amelogenin protein is considered as the major molecular marker of developing and mineralizing ectodermal enamel. It regulates the shape, size, and direction of growth of the enamel mineral crystallite. Recent data suggest other roles for amelogenin beyond regulation of enamel mineral crystal growth. The present study describes our recent discovery of amelogenin expression in soft tissues: in brain and in cells of the hematopoietic system, such as macrophages, megakaryocytes and in some of the hematopoietic stem cells. Reverse transcription-polymerase chain reaction (RT-PCR) followed by cDNA sequencing revealed, in mouse brain, two amelogenin mRNA isoforms: the full-length amelogenin including exon 4, and the isoform lacking exon 4. Immunohistochemistry revealed amelogenin expression in brain glial cells. Mouse macrophages were found to express the full-length amelogenin sequence lacking exon 4. Confocal microscopy revealed colocalization of amelogenin and CD41 (a megakaryocyte marker), as well as amelogenin and CD34 (a hematopoietic stem cell marker) in some of the bone marrow cells. The expression of amelogenin, a major structural protein of the mineralizing extracellular enamel matrix, also in cells of non-mineralizing soft tissues, suggests that amelogenin is multifunctional. Several different potential functions of amelogenin are discussed.


Microfluidic Chip for the Photocatalytic Production of Active Chlorine.
Active chlorine is the most powerful microbicidal reagent in swimming pools, potable water, hospitals, and medical surgeries. Its production mainly relies on reactive inorganic intermediates and electrochemical methods that involve undesired waste products and high energy as well as material costs. In this study, we fabricated a low-cost chip based on sputter-coated thin films of silver (Ag) that acted as recyclable and effective photoelectrode for the photocatalytic production of active chlorine (HOCl) from aqueous media and artificial sunlight. The photoelectrode was electrochemically activated to AgCl at low overpotentials between 0.2 and 0.4 V vs Ag|AgCl (3 M KCl) and photocatalytically reduced to Ag(0) for 15 consecutive cycles, showing the electrode still being active. However, because of poor adhesion properties on the selected substrates, degradation effects were observed over time. Furthermore, the Ag@AgCl photoelectrode was integrated into a microfluidic chip, and we showed for the first time a light-driven microfluidic chip generating a constant stream of active chlorine.


The effect of salts on the stability of the H2A-H2B histone dimer.
The core nucleosome, which comprises an H3-H4 tetramer and two H2A-H2B dimers, is not a static DNA packaging structure. The nucleosome is a dynamic protein-DNA complex, and the modulation of its structure is an important component of transcriptional regulation. To begin to understand the molecular details of nucleosome dynamics, we have investigated the stability of the isolated H2A-H2B dimer. The urea-induced equilibrium responses of the heterodimer have been examined by far-UV circular dichroism and intrinsic tyrosine fluorescence. The two spectroscopic probes yielded coincident transitions, and global fitting of the reversible urea-induced unfolding further demonstrated that H2A-H2B unfolds by a two-state equilibrium response. At physiological ionic strengths, the free energy of unfolding in the absence of urea of H2A-H2B is 11.8 +/- 0.3 kcal mol(-)(1), moderate stability for a dimer of 26.4 kDa. The m value, or sensitivity of the unfolding to urea, is 2.9 +/- 0.1 kcal mol(-)(1) M(-)(1). This value is significantly larger than would be predicted for the unfolding of the dimerization motif alone ( approximately 2 kcal mol(-)(1) M(-)(1)), suggesting that the N-terminal tails may adopt a collapsed, solvent-excluding structure that undergoes an unfolding transition. The efficacies of several potassium salts and three chloride salts to stabilize the H2A-H2B dimer were determined. The salt-dependent stabilization of the H2A-H2B dimer shows that the Hofmeister effect is the predominant mode of stabilization. However, studies employing multiple salts suggest that there is a component of stabilization that must arise from screening of electrostatic repulsion in the highly basic heterodimer. The most highly charged regions of the dimer are the N-terminal tails, sites of posttranslational modifications such as acetylation and phosphorylation. These modifications, which alter the charge density of the tails, are involved in regulation of nucleosome dynamics.


A simple method for the preparation of pseudopure states in nuclear magnetic resonance quantum information processing.
The use of nuclear magnetic resonance (NMR) to carry out quantum information processing (QIP) often requires the preparation, transformation, and detection of pseudopure states. In our previous work, it was shown that the use of pairs of pseudopure states (POPS) as a basis for QIP is very convenient because of the simplicity in experimental execution. It is now further demonstrated that the product of the NMR spectra corresponding to two sets of POPS that share a common pseudopure state has the same peak frequencies as those of the common (single) pseudopure state. Examples of applying two different quantum logic gates to a 5-qubit system are given.


Fasting serum bile acids concentration is associated with insulin resistance independently of diabetes status.
Background Bile acids (BAs) have been demonstrated to exert a variety of metabolic effects and alterations in BAs have been reported in patients with obesity, insulin resistance (IR) and type 2 diabetes mellitus (T2DM). However, it is unclear which metabolic condition is the main contributor to alterations in BAs. In this study, we investigate the associations between different BA profiles with glycemia, obesity or IR status. Methods Fasting serum concentrations of 15 BA species were determined in a total of 241 individuals (71 drug-naïve patients with T2DM, 95 patients with impaired fasting glucose [IFG], and 75 healthy controls. Results A comparison of the mean values of the BAs revealed no significant differences between normoglycemic controls and patients with IFG or T2DM. However, when the entire cohort was divided according to the presence of IR as determined by a homeostasis model assessment of insulin resistance (HOMA-IR) value >2.5, the levels of total BA and most species of BAs were significantly higher in patients with IR than in patients without. In the correlation analysis, most species of BAs, as well as total BA, were significantly associated with HOMA-IR levels. Furthermore, when the subjects were divided into four groups according to IR and diabetic status, subjects with IR had significantly higher total BAs than participants without IR both in diabetic and non-diabetic groups. Ultimately, multiple linear regression analysis identified HOMA-IR as the only significant contributor to most serum BA species. Conclusions Our findings support the essential role of IR in regulating BA metabolism and that this effect is independent of diabetic status.


Detection of ketosis in vitreous at autopsy after embalming.
Ketosis occurs in ketoacidosis or malnourishment. When either is suspected in relation to a death, it may be important to analyze for ketosis at autopsy. We encountered a case where starvation was suspected in a deceased nursing home resident, where the body had been embalmed prior to autopsy. Gas chromatography (GC) was unable to separate acetone from formaldehyde, a component of embalming fluid. The Acetest is a simple test that can detect acetone and acetoacetate in body fluids. We validated the Acetest with GC on vitreous. The Acetest and GC were consistent except at very low levels of acetone or acetoacetate. The sensitivity of the Acetest for acetoacetate in vitreous was 10 mg/dL, consistent with early starvation. Significant interference from embalming fluid did not occur. The Acetest was negative in the described case. The Acetest is a simple and useful test for the detection of ketosis in embalmed autopsies.


The precision of anatomical normalization in the medial temporal lobe using spatial basis functions.
We investigated the accuracy of spatial basis function normalization using anatomical landmarks to determine how precisely homologous regions are colocalized. We examined precision in terms of: (1) the number of nonlinear basis functions used by the normalization procedure; (2) the degree of (Bayesian) regularization; and (3) the effect of substituting different templates and how this interacted with the number of basis functions. The face validity of spatial normalization was assessed as a function of these parameters, using the colocalization of homologous landmarks in a test sample of 20 normally developing children and 5 children with bilateral hippocampal pathology. Our results suggest that when optimal normalization parameters are used, anatomical landmarks in the medial temporal lobes are colocalized to within a standard deviation of about 1 mm. When suboptimal parameters are used this standard deviation can increase up to 3 mm. Interestingly the optimal parameters are those that provide a rather constrained normalization as opposed to those that optimize intensity matching at the expense of rendering the warps "unlikely." The implications of our results, for users of voxel-based morphometry, are discussed.


[Gestational diabetes mellitus. Experience at a third level hospital].
The prevalence of type 2 diabetes mellitus and of gestational diabetes mellitus is high in the Mexican population; thus, strategies to improve its detection and prevent obstetric and perinatal complications are essential. During the period 2000-2004 a total of 8,074 pregnant women were studied from the day of performance, 50-g, 1 hour glucose screening test for gestational diabetes mellitus (ST-GDM) until the end of pregnancy using the same protocol: ST-GDM was performed immediately after 14 weeks of gestation in high-risk women and between 24-28 weeks in those with regular risk. Two weeks later 100-g, 3 hour oral glucose tolerance test (3h-OGTT) was performed in women with ST-GDM [symbol: see text] 130 but < 180 mg/dL, and patients were classified according to Freinkel's criteria in class A1, A2 and B1 gestational diabetes mellitus. All women received a diet according to their ideal weight for gestational age and, when necessary, insulin was added to achieve an adequate glycemic control. From 8,074 glucose screening tests for gestational diabetes mellitus, 37.2% (n = 2,997) were positive and 17.2% (n = 514) diagnostic for gestational diabetes mellitus (serum glucose [symbol: see text] 180 mg/dL). In 2,483 patients, ST-GDM was positive but negative for gestational diabetes (serum glucose >130 but <180 mg/dL); in 1,070 of them (43.0%) gestational diabetes mellitus was diagnosed by means of 3h-OGTT. The diagnosis of class A1 gestational diabetes mellitus was done in 908 patients (84.9%), A2 in 188 (11.8%) and B1 in 51 (3.2%). Patients with gestational diabetes diagnosed only by an abnormal ST-GDM were classified as class A1 gestational diabetes mellitus. Gestational age at diagnosis by ST-GDM was 12.4 +/- 4.7 weeks and 27.4 +/- 5.8 weeks when diagnosed by a 3h-OGTT. The total daily dose of insulin required was related to Freinkel's classification: 16.0% (n = 215/1,345) with class A1 gestational diabetes mellitus required 0.48 +/- 0.33 U/day/kg and 85.0% (n = 43/51) with class B1 needed 1.0 +/- 0.32 U/day/kg at the end of pregnancy, which occurred at 38.2 +/- 2.0 weeks in all 3 groups. In decreasing order of occurrence perinatal complications were: pregnancy-induced hypertension (specially in class B1 gestational diabetes mellitus), urinary tract infections and premature rupture of membranes. Birth weights either < 2,500 g or > 4,000 g were more frequent among women with class B1 gestational diabetes, than in the other 2 groups. After pregnancy ended (6-8 weeks), 52.2% of women with gestational diabetes (mostly class B1) was diagnosed with permanent type 2 diabetes mellitus. In this study the percentage of pregnant women diagnosed as having gestational diabetes mellitus exclusively by ST-GDM was high (17.2%). Freinkel's classification of such disease predicted higher risk in women with class B1 gestational diabetes mellitus for: 1) obstetric complications, 2) higher doses of insulin to achieve an adequate glycemic control; 3) newborns' birth weight < 2,500 g or > 4,000 g for gestational age, 4) having type 2 diabetes mellitus in late puerperium.


Bottle microresonator with actively stabilized evanescent coupling.
The evanescent coupling of light between a whispering-gallery-mode bottle microresonator and a subwavelength-diameter coupling fiber is actively stabilized by means of the Pound-Drever-Hall technique. We demonstrate the stabilization of a critically coupled resonator with a control bandwidth of 0.1 Hz, yielding a residual transmission of (9±3)×10(-3) for more than an hour. Simultaneously, the frequency of the resonator mode is actively stabilized.


[Invasive ventilation. Classification, technique and clinical experiences with BiPAP/APRV (Biphasic Positive Airway Pressure/Airway Pressure Release Ventilation)].
BiPAP (bilevel or biphasic positive airway pressure) and APRV (airway pressure release ventilation) are new, and from a technical viewpoint closely related techniques recently introduced to the field of invasive ventilatory support. BiPAP/APRV can be described as a pressure controlled continuous high flow positive airway pressure system with a time-cycled change between a high inspiratory pressure level and a lower expiratory pressure level. Due to highly sensitive valves placed in the inspiratory and expiratory part of the system, unrestricted spontaneous breathing is possible at any moment of the mechanically supported ventilatory cycle. During invasive ventilation BiPAP offers potential advantages by allowing unrestricted spontaneous breathing thus reducing the need for sedation and facilitating weaning. APRV has primarily been investigated in conditions of moderate to severe acute lung injury and it seems that APRV is associated with less detrimental effects on the cardiopulmonary system compared to conventional ventilatory strategies. Apart from a review of the literature the article gives a classification and a technical description of the systems and focuses on the practical approach to BiPAP/APRV, e.g. the initiation and adjustment of respiratory support and the weaning from ventilatory support when applying these techniques.


Variation in the use of medicines by ethnicity during 2006/07 in New Zealand: a preliminary analysis.
To describe variations in dispensing of specific medication groups by ethnicity in New Zealand, adjusting for health need. Preliminary linkage of dispensings of prescription medicines in 2006/07 to age/disease burden proxies of health need for Maori, Pacific peoples (Pasifika)--who are mostly of Samoan, Tongan, Niuean, or Cook Islands descent--in New Zealand, and non-Maori/non-Pasifika. These disease burden proxies combine differences in prevalence, age, morbidity, and mortality. Variations were disaggregated by patients being first dispensed medicines ('access') versus subsequent dispensings ('persistence'). Initially, overall age-adjusted incidence of 'scripts' (prescriptions dispensed) to Maori was similar to that of non-Maori. There were differences in therapeutic coverage between Maori and Pasifika, for example greater use of asthma medicines in Maori. However, further adjustments linking with disease burden showed marked variance for a number of diseases. Differences in dispensing included areas of high health need such as heart disease, infections, diabetes, mental health and respiratory disease. Maori had 19-37% lower dispensings overall than non-Maori, with a net difference of nearly 1 million scripts. Maori were both less likely to access medicines, and then after first dispensing had fewer subsequent scripts. Patterns for Pasifika appeared similar, although needs-adjusted analysis is awaited for this population. Once adjusting for need, there was variable but sizeable differences in medicines dispensed to Maori compared with non-Maori, and likely differences for Pasifika populations. There are however important limitations to this preliminary analysis. Crude and age-standardised metrics may be poor predictors of needs-adjusted gaps in medicines use. In this analysis, solely age-standardised rates tended to underestimate differences once adjusting for burden of disease; future analyses of prescribing patterns should consider better adjusting for disease burden.


Reactivity of a (mu-oxo)(mu-hydroxo)diiron(III) diamond core with water, urea, substituted ureas, and acetamide.
A series of iron(III) complexes of the tetradentate ligand BPMEN (N,N'-dimethyl-N,N'-bis(2-pyridylmethyl)ethane-1,2-diamine) were prepared and structurally characterized. Complex [Fe(2)(mu-O)(mu-OH)(BPMEN)(2)](ClO(4))(3) (1) contains a (mu-oxo)(mu-hydroxo)diiron(III) diamond core. Complex [Fe(BPMEN)(urea)(OEt)](ClO(4))(2) (2) is a rare example of a mononuclear non-heme iron(III) alkoxide complex. Complexes [Fe(2)(mu-O)(mu-OC(NH(2))NH)(BPMEN)(2)](ClO(4))(3) (3) and [Fe(2)(mu-O)(mu-OC(NHMe)NH)(BPMEN)(2)](ClO(4))(3) (4) feature N,O-bridging deprotonated urea ligands. The kinetics and equilibrium of the reactions of 1 with ligands L (L = water, urea, 1-methylurea, 1,1-dimethylurea, 1,3-dimethylurea, 1,1,3,3-tetramethylurea, and acetamide) in acetonitrile solutions were studied by stopped-flow UV-vis spectrophotometry, NMR, and mass spectrometry. All these ligands react with 1 in a rapid equilibrium, opening the four-membered Fe(III)(mu-O)(mu-OH)Fe(III) core and forming intermediates with a (HO)Fe(III)(mu-O)Fe(III)(L) core. The entropy and enthalpy for urea binding through oxygen are DeltaH degrees = -25 kJ mol(-1) and DeltaS degrees = -53.4 J mol(-1) K(-1) with an equilibrium constant of K(1) = 37 L mol(-1) at 25 degrees C. Addition of methyl groups on one of the urea nitrogen did not affect this reaction, but the addition of methyl groups on both nitrogens considerably decreased the value of K(1). An opening of the hydroxo bridge in the diamond core complex [Fe(2)(mu-O)(mu-OH)(BPMEN)(2)] is a rapid associative process, with activation enthalpy of about 60 kJ mol(-1) and activation entropies ranging from -25 to -43 J mol(-1) K(-1). For the incoming ligands with the -CONH(2) functionality (urea, 1-methylurea, 1,1-dimethylurea, and acetamide), a second, slow step occurs, leading to the formation of stable N,O-coordinated amidate diiron(III) species such as 3 and 4. The rate of this ring-closure reaction is controlled by the steric bulk of the incoming ligand and by the acidity of the amide group.


Genetic requirements for local and systemic movement of tomato golden mosaic virus in infected plants.
Tomato golden mosaic geminivirus (TGMV) has two DNA components, A and B. Replication of DNA A can be detected in inoculated leaves, but DNA B is additionally required for virus movement in planta. Using viral DNA accumulation as an indication of the number of infected cells, we show here that both the BL1 and BR1 genes are necessary for local TGMV movement. We also demonstrate that transient expression of BL1 and BR1 together allows wild-type TGMV DNA A to move systemically. When the transient movement assay was used to analyze various A component mutants, all were found to move locally in inoculated leaves, and only an ar1 (coat protein) mutant was unable to move systemically. In addition, we confirm that a TGMV al2 (AR1 and BR1 trans-activator) mutant has a defect in local movement which can be rescued by provision of exogenous BR1, but not BL1. Finally, we show that the ability of TGMV coat protein mutants to accumulate single-stranded (ss) DNA is dependent on BR1. These results provide experimental evidence obtained in planta which supports three predictions of published models for bipartite geminivirus movement: (i) BL1 and BR1 have distinct and essential roles in cell-to-cell movement as well as systemic movement; (ii) BR1 may interact with viral ssDNA in vivo; and (iii) AL2 is indirectly required for movement through its effect on BR1 expression. In addition, our data suggest that specific models of bipartite geminivirus systemic movement should accommodate a role for the coat protein.


Haploidentical Stem Cell Transplant With Post-transplant Cyclophosphamide for Chediak-Higashi Syndrome: A Very Rare Case Report.
Chediak-Higashi syndrome is a rare immunodeficiency disorder for which hematopoietic stem cell transplant (HSCT) is the only curative treatment option. HSCT only corrects the hematologic and immunologic manifestations of the disease but neurologic complications may still progress after transplant. Haploidentical HSCT (haplo-HSCT) has evolved as a feasible alternative for patients with primary immunodeficiency. More recently, there has been use of haplo-HSCT with post-transplant cyclophosphamide. However, only 4 cases of Chediak-Higashi syndrome have been reported using this approach. Here, the authors describe a case of a 17-month-old boy who was successfully treated by haplo-HSCT with reduced-toxicity conditioning (fludarabine/treosulfan/melphalan) and post-transplant cyclophosphamide.


Light activates H2 15O flow in rice: Detailed monitoring using a positron-emitting tracer imaging system (PETIS).
Water (H2 15O) translocation from the roots to the top of rice plants (Oryza saliva L. cv. Nipponbare) was visualized over time by a positron-emitting tracer imaging system (PETIS). H2 15O flow was activated 8 min after plants were exposed to bright light (1 500 &mgr;mol m-2 s-1). When the light was subsequently removed, the flow gradually slowed and completely stopped after 12 min. In plants exposed to low light (500 &mgr;mol m-2 s-1), H2 15O flow was activated more slowly, and a higher translocation rate of H2 15O was observed in the same low light at the end of the next dark period. NaCl (80 mM) and methylmercury (1 mM) directly suppressed absorption of H2 15O by the roots, while methionine sulfoximine (1 mM), abscisic acid (10 &mgr;M) and carbonyl cyanide m-chlorophenylhydrazone (10 mM) were transported to the leaves and enhanced stomatal closure, reducing H2 15O translocation.


Duplications of the alimentary tract in children.
This study was conducted to assess the clinical, diagnostic and therapeutic approach in patients with alimentary tract duplication and review the relevant literature. A retrospective analysis of 28 patients of alimentary tract duplications treated between January 1990-December 1999 was carried out. There was a male preponderance (25:3); 71% of the patients were under 2 years of age. The presenting features were related to the anatomic location. Three patients were diagnosed antenatally. Real time ultrasonography and CT scan was undertaken for preoperative evaluation in the majority of patients. In selected cases a 99m-Tc-pertechnetate scan and barium meal follow through examination were also performed. Majority of duplications were in the jejunum and ileum. Twenty percent of our patients had thoracoabdominal duplication as compared to 2% reported in literature. Four patients required to be operated upon in the emergency for related complications. In the remaining patients complete excision of the cyst was done in 21 and only mucosectomy in 3 patients. Because these lesions are rare and can present with a wide range of clinical manifestations or may even be encountered intraoperatively, the appropriate surgical management requires the surgeon to be familiar with the anatomy and clinical characteristics of these lesions.


A method to minimise error in 2D-DLT reconstruction of non-planar markers filmed with a moving camera.
This article describes a method that allows estimating, with the 2D version of the direct linear transformation (DLT), the actual 2D coordinates of a point when the latter is not strictly in the calibration plane. Markers placed in vertical line, above, below and in the centre of a horizontal calibration plane were filmed by a moving camera. Without correction, strong errors (up to 64.5%) were noticed for markers out of the calibration plane. After correction, calculated coordinates were consistent with actual values (error < 0.55%). The method was then applied to slip distance measurement, using a marker fixed on the hoof of a horse trotting on a calibrated track while being followed with a camera. The correction effect represented 6.6% of slip distance. Combined with the 2D-DLT transformation, the proposed corrective method allows an accurate measurement of slip distances, for high-speed outdoor locomotion analysis, using a moving camera.


Left atrial deformation and nonischemic dilated cardiomyopathy. A 2D speckle-tracking imaging study.
Left ventricular filling pressure (LVFP) is raised by the compromised contraction and impaired ventricular compliance in dilated hearts with systolic dysfunction. Timely recognition and staging of this condition are important for planning of the treatment strategy and making the prognosis. Two-dimensional speckle- tracking echocardiography (2D-STE) has recently enabled the quantification of left atrial (LA) myocardial deformation dynamics. In this study, echocardiographic indicators of increased LVFP and NT-pro-BNP were compared with LA strain measured by 2D-STE. A total of 49 nonischemic dilated cardiomyopathy (DCMP) patients were included in the study. All patients underwent standard 2D echocardiography. In the 2D-STE analysis of the LA, global longitudinal LA strain during ventricular systole (GLAs-res) and strain during late diastole (GLAs-pump) were obtained. NT-pro-BNP levels were measured. The patients were divided into two groups--normal (group 1) and increased (group 2) LVFP--according to E/A ratio, E velocity, and E/E' ratio. LAVi-max, LAVi-min, and NT-pro-BNP were higher in group 2, whereas LAtotalEF, LAactiveEF, GLAs-res, and GLAs-pump were lower. In univariate analysis, a good negative correlation was seen between GLAs-res vs. NT-pro-BNP, GLAs-res vs. LAVi-max, and GLAs-res vs. E/E' ratio; a good negative correlation was present between GLAs-pump vs. NT-pro-BNP, GLAs-pump vs. LAVi-max, and GLAs-pump vs. E/E' ratio. LAVi-max, LAactiveEF, NT-pro-BNP, GLas-res, and GLAs-pump were studied by logistic regression analysis. GLAs-res (p = 0.009, OR = 0.593, 95 % CI 0.4-0.877), NT-pro-BNP (p = 0.028, OR = 1.027, 95 % CI 1.003-1.052), and LAactiveEF (p = 0.022, OR = 0.001, 95 % CI 0.001-0.024) were found to be independent predictors of increased LVFP. 2D-STE-based LA function is impaired in patients with nonischemic DCMP. LA reservoir and pump function parameters together with NT-pro-BNP levels might be useful in estimating LVFP in this patient group.


[Value of CT-guided biopsy in malignant lymphoma].
Management of diagnosing malignant lymphomas has changed with development of CT-guided techniques and reliable biopsy tools. Pathologists can use representative tissue samples for sub classification in more than 90%. Evaluation of residual lymphoma or relapse can be nearly as effective. Therefore percutaneous biopsy can be considered as primary diagnostic tool in the absence of peripheral lymphadenopathy. CT-guided biopsies can be performed on an outpatient basis under conscious sedation considering contraindications as well as regional complications. Acceptance of percutaneous biopsy by the pathologist and oncologist is based on diagnostic effectiveness that is significantly improved if more than 3 dagger solid tissue samples are taken. This article reviews the value of CT-guided biopsy in comparison to surgical procedures in patients with malignant lymphoma. Essential aspects that lead to a diagnostic percutaneous biopsy are discussed on grounds of the current literature.


Novel potassium binders to optimize RAASi therapy in heart failure: A systematic review and meta-analysis.
Hyperkalemia often occurs among heart failure (HF) patients, particularly when treated with renin-angiotensin-aldosterone system inhibitors (RAASi). Even modest potassium levels variations raise the risk of mortality and prompt patients to discontinue disease-modifying treatment, as RAASi. Novel potassium binders (NPB), patiromer and sodium zirconium cyclosilicate, are effective in reducing potassium levels and are approved for the treatment of hyperkalemia in HF, but whether their use results in a real optimization of HF treatment remains to be seen. The aim of the present meta-analysis was to assess the efficacy of NPB on the optimization of RAASi therapy in HF patients. PubMed, Web of Science and Clinicaltrial.gov were searched without restrictions from inception to 06 August 2022 to identify valuable articles. The studies that met the inclusion criteria were analyzed. The prespecified primary outcome was the optimization of RAASi therapy in HF patients, defined as the proportion of patients on RAASi at the end of follow-up. Secondary outcomes were hyperkalemia events, reduction in potassium levels, and adverse drugs reactions. Six studies with a total of 1390 patients were included. NPB improved RAASi therapy optimization in HF by 14% (95% CI: 4-26%), decreased hyperkalemia events by 29% (95% CI: 55-92%), and reduced potassium levels by 0.31 mEq/L (95% CI: 0.18-0.44) compared to placebo, maintaining a good safety profile. NPB are effective in allowing RAASi therapy optimization in patients affected by HF, in reducing hyperkalemia events and potassium levels. CRD42022351811 URL: https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=351811.


A socio-ecologic model for periodontal diseases.
A socio-ecologic conceptual model for periodontal diseases has been proposed. The model, which includes 4 items: health-care organization, human biology, behavioral factors, and environment, has been tested on a random-sample of 50-year-old Oslo citizens. The investigation is based on a clinical examination as well as a questionnaire and structured interview. A logistic regression model was used to study associations between risk factors and the probability of deep periodontal pockets (> 5.5 mm). The risk of periodontal pockets was positively associated with: short duration of education, being of male gender, previous periodontal treatment, poor oral hygiene and infrequent toothbrushing. Variables describing behavioral factors and human biology were the items found to be most closely associated with periodontal pocketing.


Metal substitution of Neurospora copper metallothionein.
The binding of diamagnetic Zn(II), Cd(II), and Hg(II) and paramagnetic Co(II) and Ni(II) ions to the apo form of Neurospora metallothionein (MT) was investigated by various spectroscopic techniques. In contrast to native copper MT, which was shown to bind 6 mol of Cu(I)/mol of protein (Lerch, 1980), all substituted forms reveal an overall metal to protein stoichiometry of 3. The charge-transfer (CT) transitions of the complexes containing diamagnetic metal ions as well as the d-d transitions of those with paramagnetic metal ions are indicative of a distorted Td coordination. Electron paramagnetic resonance and absorption measurements of the Co(II) derivative are in agreement with the presence of a metal-thiolate cluster in this protein. Metal titration studies of the apoprotein reveal characteristic spectral features for the derivatives containing two metal equivalents as compared to those with a full complement of three metal ions. The former features are indicative of an exclusive Td type of metal-sulfur coordination whereas the latter suggest that the third metal ion is coordinated in a different fashion. This finding is in agreement with the presence of only seven cysteine residues in Neurospora MT as opposed to nine cysteine residues in the three-metal cluster of the mammalian MT's [Winge, D.R., & Miklossy, K.-A. (1982) J. Biol. Chem. 257, 3471].


Community-Level Physiological Profiling for Microbial Community Function in Broiler Ceca.
Poultry production is a major agricultural output worldwide. It is known that the gut health of broilers is essential for their growth and for providing wholesome products for human consumption. Previously, the microbial diversity of broiler ceca was studied at the genetic level. However, the functional diversity and metabolic activity of broiler cecal bacterial communities are not fully investigated. Recently, the EcoPlates™ from Biolog, Inc. have been used for characterizing bacterial communities from various environments. In this study, we applied these plates to physiologically profile cecal bacterial communities in broilers. The ceca were aseptically excised from 6-week-old broilers, and their contents were suspended in phosphate buffered saline. The cultures in the EcoPlates™ were incubated at 42 °C for 5 days in an OmniLog® system. Responses of the bacterial communities to the various chemicals as carbon sources were measured on formazan production. The results show sigmoidal growth curves with three phases in all 12 cecal samples. Cecal bacterial communities could not use 11 carbon substrates for carbon sources; instead, they used pyruvic acid methyl ester, glycogen, glucose-1-phosphate and N-acetyl-D-glucosamine most frequently. Each bacterial community metabolized various numbers of the substrates at different rates among broilers. In the future, modification of the culture conditions to mimic the gut environment is needed. More investigations on the effects of nutrients, Salmonella or Campylobacter on physiological functions of cecal bacterial communities will provide insights into the improvement of animal well-being, saving production expenditures for producers and providing safer poultry products for human consumption.


Effects of ulinastatin, a urinary trypsin inhibitor, on synaptic plasticity and spatial memory in a rat model of cerebral ischemia/reperfusion injury.
Established therapies for cerebral ischemia-reperfusion injury are currently limited. The urinary trypsin inhibitor ulinastatin (UTI) is considered cytoprotective against ischemia-reperfusion injury in internal organs through its anti-inflammatory activity. We aimed to investigate the neuroprotective effects of UTI on learning and memory of rats after cerebral ischemia-reperfusion injury. Rats were treated with UTI at 10,000 U/kg body weight, then underwent ischemia and reperfusion by the middle cerebral arterial occlusion (MCAO) method. At various times after the onset of reperfusion, we evaluated neurologic impairment scores. Brain sections underwent immunohistochemical staining for synaptophysin and calcium-binding protein S100β. Other rats underwent the Morris water maze test to determine the effects of UTI on learning and memory. Spatial reference learning and memory were improved with UTI treatment by down-regulating S100β-positive cells and preventing the loss of neural cells. Thus, UTI has a neuroprotective role on synaptic plasticity and spatial memory with cerebral ischemia-reperfusion injury in rats.


Endothelial progenitor cells and endothelial vesicles - what is the significance for patients with chronic kidney disease?
Endothelial progenitor cells are cells derived from the bone marrow that circulate in the bloodstream and can exhibit phenotypic characteristics of endothelial cells. They are thought to be involved in postnatal vasculogenesis and to potentially help repair injured endothelium. Circulating endothelial cells are mature endothelial cells in the circulation, and endothelial vesicles or microparticles are thought to be derived from the membranes of endothelial cells as a result of injury or activation. Recent research has focused on using these markers of endothelial injury and repair to assess the state of endothelial health. These efforts have been hampered by lack of uniformity in methodology and terminology. Recent developments in flow cytometry techniques have allowed better characterization and definition of these cells. We review the common techniques used to identify and isolate these cells, clinical studies in patients with chronic kidney disease (CKD) where they serve as markers of endothelial health and predictors of outcome, and possible mechanisms of progenitor cell dysfunction in CKD.


Evaluation of systematic errors for the continuous-wave NO2 differential absorption lidar employing a multimode laser diode.
The NO2-differential absorption lidar (NO2-DIAL) technique has been of great interest for atmospheric NO2 profiling. Comprehensive studies on measurement errors in the NO2-DIAL technique are vital for the accurate retrieval of the NO2 concentration. This work investigates the systematic errors of the recently developed continuous-wave (CW) NO2-DIAL technique based on the Scheimpflug principle and a high-power CW multimode laser diode. Systematic errors introduced by various factors, e.g., uncertainty of the NO2 differential absorption cross-section, differential absorption due to other gases, spectral drifting of the λon and λoff wavelengths, wavelength-dependent extinction and backscattering effect, have been theoretically and experimentally studied for the CW-DIAL technique. By performing real-time spectral monitoring on the emission spectrum of the laser diode, the effect of spectral drifting on the NO2 differential absorption cross-section is negligible. The temperature-dependent NO2 absorption cross-section in the region of 220-294 K can be interpolated by employing a linear fitting method based on high-precision absorption spectra at 220, 240, and 294 K. The relative error for the retrieval of the NO2 concentration is estimated to be less than 0.34% when employing the interpolated spectrum. The primary interference molecule is found to be the glyoxal (CHOCHO), which should be carefully evaluated according to its relative concentration in respect to NO2. The systematic error introduced by the backscattering effect is subjected to the spatial variation of the aerosol load, while the extinction-induced systematic error is primarily determined by the difference between the aerosol extinction coefficients at λon and λoff wavelengths. A case study has been carried out to demonstrate the evaluation of systematic errors for practical NO2 monitoring. The comprehensive investigation on systematic errors in this work can be of great value for future NO2 monitoring using the DIAL technique.


Clinical Applications of Aspirin as a Multi-potent Drug Beyond Cardiovascular Implications: A Proof of Concept for Anesthesiologists- A Narrative Review.
To the best of our knowledge, aspirin (ASA) is known as a commonly used medication worldwide. Although the cardiovascular aspects of ASA are well-established, recently, it has been identified that ASA can yield multiple extra-cardiovascular therapeutic potencies in facing neurodegenerative disorders, various cancers, inflammatory responses, and the COVID-19 pandemic. In this review, we aimed to highlight the proven role of ASA administration in the variety of non-cardiovascular diseases, particularly in the field of anesthesiology.


Acute acoustic trauma: how to manage and how to prevent?
The consequence of an exposure to intense sounds can be a temporary or permanent hearing loss and even with a rapid therapeutic management, severe sensorineural sequelae may persist. the authors report a retrospective study about 64 patients followed for an acute acoustic trauma during a period of 8 years (2006 to 2013). For all the cases, a clinical examination associated to a pure-tone audiometry was conducted. Hearing levels were measured at the frequencies 500, 1000, 2000 and 3000 Hertz. Auditory evoked potentials were performed in 17 cases. The therapeutic and evolutive data were detailed and discussed. All our patients were male with a mean age of 34 years. The cause of acoustic trauma was a firing of a gun near the ear in 48 cases, an explosion near the ear in 5 cases and a sudden exposure to loud noises near military planes in 11 cases. Clinical complaints were acute hearing loss with tinnitus. Audiometric exams found a sensorineural hearing loss with a hearing level average of 38 decibels (dB) +/- 14 SD. The therapy consisted of systemic cortisteroids associated in all the cases to peripheral vasodilators. It was given intravenously during 10 days and then orally with vasodilators during one to 3 months. Hyperbaric oxygenotherapy have been administrated for 25 patients. The follow-up consisted of questioning about symptoms, clinical examination and pure-tone audiometry. A good evolution was noted in 52 cases (81%) and the mean of hearing level after therapy was: 24 dB +/- 12 dB. Despite a prolonged therapy with vaso-active drugs, tinnitus persisted in 36 cases. Controlling noise and its harmful effects through technical devices and safety professionals programs are the best way to reduce the frequency and the sensorineural sequelae due to acute acoustic trauma.


Detection of antibodies to hepatitis C virus in dried blood spot samples from mothers and their offspring in Lahore, Pakistan.
Dried blood spot samples from mothers and their offspring attending the obstetric and pediatric departments of two hospitals in Lahore, Pakistan, were tested for antibodies to hepatitis C virus (HCV). The seroprevalence of HCV in the women was 6.7% (95% confidence interval [CI], 4.3 to 9.1), and that in the children was 1.3% (95% CI, 0.34 to 2.26). Four anti-HCV immunoglobulin G (IgG)-positive children had mothers that were anti-HCV IgG negative, which suggested that their infection was community acquired.


Activated protein C analog protects from ischemic stroke and extends the therapeutic window of tissue-type plasminogen activator in aged female mice and hypertensive rats.
3K3A-activated protein C (APC) protects young, healthy male rodents after ischemic stroke. 3K3A-APC is currently under development as a neuroprotectant for acute ischemic stroke in humans. Stroke Therapy Academic Industry Roundtable recommends that after initial studies in young, healthy male animals, further studies should be performed in females, aged animals, and animals with comorbid conditions. Here, we studied the effects of delayed 3KA-APC therapy alone and with tissue-type plasminogen activator (tPA) in aged female mice and spontaneously hypertensive rats. We used Stroke Therapy Academic Industry Roundtable recommendations for ensuring good scientific inquiry. Murine recombinant 3K3A-APC (0.2 mg/kg) alone or with recombinant tPA (10 mg/kg) was given intravenously 4 hours after transient middle cerebral artery occlusion in aged female mice and rats and after embolic stroke in spontaneously hypertensive rat. 3K3A-APC was additionally administered within 3 to 7 days after stroke. The neuropathological analysis and neurological scores, foot-fault, forelimb asymmetry, and adhesive removal tests were performed within 7 and 28 days of stroke. In all models, tPA alone had no effects on the infarct volume or behavior. 3K3A-APC alone or with tPA reduced the infarct volume 7 days after the middle cerebral artery occlusion in aged female mice and embolic stroke in spontaneously hypertensive rat by 62% to 66% and 50% to 53%, respectively, significantly improved (P<0.05) behavior, and eliminated tPA-induced intracerebral microhemorrhages. In aged female mice, 3K3A-APC was protective within 4 weeks of stroke. 3K3A-APC protects from ischemic stroke and extends the therapeutic window of tPA in aged female mice and in spontaneously hypertensive rat with a comorbid condition.


Perioperative and Long-term Outcome of the Warshaw Technique in Laparoscopic Spleen-preserving Distal Pancreatectomy.
The purpose of this study was to compare the safety and outcomes of laparoscopic splenic vessel preservation (Lap-SVP) to those of laparoscopic Warshaw technique (Lap-WT). Fourteen patients underwent Lap-SVP and 5 patients underwent Lap-WT. Their clinical data and outcomes of the 2 procedures were compared. The operative time, intraoperative blood loss, clinically relevant pancreatic fistula, and the rate of splenic infarction were significantly higher in the patients who underwent Lap-WT than in those who underwent Lap-SVP. In both groups, the platelet count ratio and splenic volume ratio at 1 month after the operation did not differ from the preoperative values. Two patients in the Lap-WT group experienced splenic infarction, and could be observed without any treatment. The long-term outcome of Lap-WT was relevant. Therefore, Lap-WT could be a treatment option for patients who may not have undergone Lap-SVP.


Role of transabdominal ultrasonography in the diagnosis of pancreatic cystic lesions.
Pancreatic cystic lesions (PCLs) are incidental findings that are being increasingly identified because of recent advancements in abdominal imaging technologies. PCLs include different entities, with each of them having a peculiar biological behavior, and they range from benign to premalignant or malignant neoplasms. Therefore, accurate diagnosis is important to determine the best treatment strategy. As transabdominal ultrasonography (US) is noninvasive, inexpensive, and widely available, it is considered to be the most appropriate imaging modality for the initial evaluation of abdominal diseases, including PCLs, and for follow-up assessment. We present a review of the possibilities and limits of US in the diagnosis of PCLs, the technical development of US, and the ultrasonographic characteristics of PCLs.


Mismatch repair in Xenopus egg extracts: DNA strand breaks act as signals rather than excision points.
In Xenopus egg extracts, DNA strand breaks (nicks) located 3' or 5' to a mismatch cause an overall 3-fold stimulation of the repair of the mismatch in circular heteroduplex DNA molecules. The increase in mismatch repair is almost entirely due to an increase in repair of the nicked strand, which is stimulated 5-fold. Repair synthesis is centered to the mismatch site, decreases symmetrically on both sides, and its position is not significantly altered by the presence of the nick. Therefore, it appears that in the Xenopus germ cells, the mismatch repair system utilizes nicks as signals for the induction and direction of mismatch repair, but not as the start or end point for excision and resynthesis.


Genotypic differences in the synergistic effect of nitrogen and boron on the seed yield and nitrogen use efficiency of Brassica napus.
Rapeseed (Brassica napus) is highly sensitive to nitrogen (N) and boron (B) deficiency; however, the synergistic effects of these elements on rapeseed production are poorly understood. The aim of this study was to investigate the effects of co-application of N and B on seed yield, N uptake and N use efficiency (NUE) of rapeseed. Three rapeseed cultivars (W10, ZS11 and HG) were treated with different N and B application rates, and the seed yield, N uptake and NUE were examined in 2-year field experiments. The application of B fertilizer (4.5, 9 kg borax ha-1 ) improved N uptake, NUE and seed yield. However, the magnitude of increase in seed yield by B fertilization was dependent upon the rate of N supply and genotype. The benefit of B was much greater at 180 kg N ha-1 than at 0 or 60 kg N ha-1 . The combination of N and B also improved N remobilization from sources (stems and husks) to sinks (seeds) and increased N recovery efficiency (NRE). Compared with the B-inefficient cultivar W10, the B-efficient cultivars ZS11 and HG were superior in growth, seed yield, N uptake and NUE on B deficient soils. Furthermore, B-efficient cultivars showed great potential in saving N input, and the yield increased by more than 40% under B deficiency conditions. This study highlights a markedly synergistic effect of N and B nutrition on rapeseed NUE and yield production and shows that B-efficient genotypes can increase yield and reduce N inputs under B-deficient conditions. © 2021 Society of Chemical Industry.


Novel approaches for preventing acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation.
Allogeneic hematopoietic stem cell transplantation (alloHSCT) offers potential curative treatment for a wide range of malignant and nonmalignant hematological disorders. However, its success may be limited by post-transplant acute graft-versus-host disease (aGVHD), a systemic syndrome in which donor's immune cells attack healthy tissues in the immunocompromised host. aGVHD is one of the main causes of morbidity and mortality after alloHSCT. Despite standard GVHD prophylaxis regimens, aGVHD still develops in approximately 40-60% of alloHSCT recipients. In this review, after a brief summary of current knowledge on the pathogenesis of aGVHD, the authors review the current combination of a calcineurin inhibitor with an antimetabolite with or without added anti-thymocyte globulin (ATG) and emerging strategies for GVHD prevention. A new understanding of the involvement of cytokines, intracellular signaling pathways, epigenetics and immunoregulatory cells in GVHD pathogenesis will lead to new standards for aGVHD prophylaxis allowing better prevention of severe aGVHD without affecting graft-versus-tumor effects.