Characterization of a novel non-receptor tyrosine kinase Src from Litopenaeus vannamei and its response to white spot syndrome virus infection.
Src family kinases (SFKs), a class of non-receptor tyrosine kinases, mediate a wide aspect of cellular signaling pathways that regulate cell proliferation, differentiation, motility and survival. In this study, we identified and characterized for the first time a novel SFK homologue from Litopenaeus vannamei (designated as LvSrc). Sequence analysis showed that LvSrc had a high homology with the identified SFKs, especially those from invertebrates. LvSrc contained the conserved SH3, SH2 and tyrosine kinase domains, as well as the potential phosphorylation and lipid modification sites. Immunofluorescence analysis demonstrated that LvSrc was mostly localized at the plasma membrane and partly resided in the perinuclear vesicle and nucleus or whole cell. Infection with white spot syndrome virus (WSSV) could up-regulate the transcription and expression levels of LvSrc and further induced its phosphorylation, suggesting that LvSrc was implicated in WSSV infection. Furthermore, our co-immunoprecipitation result confirmed the interaction between Src and focal adhesion kinase (FAK) in shrimp, while the phosphorylation of FAK was markedly enhanced by co-expression with LvSrc. In sum, our studies suggested that LvSrc might act in the FAK-regulated signaling pathway during WSSV infection, which would give us a better insight in understanding the role of SKFs in host-virus interactions in crustaceans.


Fat intakes of children with PKU on low phenylalanine diets.
As part of a study on the effects of a fat-supplemented phenylalanine (phe)-free protein substitute on the fatty acid status of children with phenylketonuria (PKU), the adequacy of the diets of children aged 1-10 years for fat and essential fatty acids (EFA) was assessed. Subjects randomized in a 1 : 1 ratio to a phe-free protein substitute supplemented with EFA (test-treatment group) or a phe-free, fat-free protein substitute (control group) for 20 weeks. 3-day semi-weighed records of food intakes collected at the end of the study period. Total fat and alpha-linolenic acid (alpha-LA) intakes were found to be poor in the control group (n = 19). Those in the test-treatment group (n = 24) had higher fat and EFA intakes (P < 0.05), bringing intakes closer to population norms. The youngest children (<5 years of age) in the control group appeared to be especially vulnerable to poor fat intakes because of the restricted diversity of their diets and, regardless of age, alpha-LA intakes by this group were poor compared with the non-PKU population. The quantity and quality of fat in the diets of children with PKU, in particular young children, should be given careful consideration in trying to optimize the ratio of linoleic acid: alpha-LA in their diets and in satisfying the requirements of this group for fat and alpha-LA.


A biocatalytic route to P-chirogenic compounds by lipase-catalyzed desymmetrization of a prochiral phosphine-borane.
[reaction: see text] Available methods for synthesis of P-chirogenic compounds are limited. We set out to find biocatalytical means to introduce asymmetry in a phosphine-borane. After screening different lipases, Candida antarctica lipase B was found to give excellent results in the desymmetrization of prochiral phosphine-boranes. Both enantiomers can be obtained in up to >98% optical purity via acetylation or hydrolysis in processes that allow recycling of the substrates.


Acquired jejunoileal diverticular disease: subject review.
Of 519 consecutive patients examined by enteroclysis, 12 (2.3%) were found to have acquired diverticula of the jejunum and ileum. All except one patient had multiple diverticula, most occurring in the jejunum. In only one patient could symptoms be ascribed to the abnormality. The combination of intraluminal distention and extrinsic abdominal compression provided by the enteroclysis technique appears to be the most reliable method for the demonstration of small-bowel diverticula. A discussion of the complications that may result from acquired jejunoileal diverticulosis and a review of the literature are presented.


Properties and regulation of the renal vacuolar H(+)-ATPase and H(+)-K(+)-ATPase.
Two proton-transporting ATPases participate in active proton transport in the nephron: the electrogenic vacuolar H(+)-ATPase and the electroneutral H(+)-K(+)-ATPase. The vacuolar H(+)-ATPase participates in proximal and distal hydrogen ion secretion related to acid-base homeostasis. The H(+)-K(+)-ATPase is located exclusively in the distal nephron, and its primary role may be in active potassium reabsorption. The properties, distribution, and regulation of these two enzymes are discussed.


Re-Thinking Elective Single Embryo Transfer: Increased Risk of Monochorionic Twinning - A Systematic Review.
Multiple pregnancies have tripled in the United States over the past 3 decades. Attributed to increasing maternal age at delivery but more so assisted reproductive technological advances, an effort has been made to decrease twinning through elective single embryo transfer. We sought to review and evaluate risks of monochorionic twinning as a predictable consequence of increasing utilization of elective single embryo transfer on perinatal outcomes. Primary outcomes included twinning rates, fetal anomalies, growth, preterm birth, and mortality. Secondary outcomes included neurological and pulmonary disability, intrauterine growth restriction, and congenital cardiac anomalies and twin-twin transfusion syndrome. PubMed and Embase. A total of 106 studies identified by systematic search met the inclusion criteria. The trend for lower numbers of embryos transferred has inadvertently led to an increase in monochorionic twinning. This is associated with worse outcomes compared to dichorionic twinning and singleton gestations for all outcomes studied. Of great concern for monochorionic twins is the risk profile of significant morbidity and mortality. Transfer of 2 embryos should be considered to avoid higher risks inherent to the shared placental phenomena related to monochorionic twins.


Imaging ion-molecule reactions: charge transfer and C-N bond formation in the C(+) + NH3 system.
The velocity mapping ion imaging method is applied to the ion-molecule reactions occurring between C(+) and NH(3). The velocity space images are collected over the relative collision energy range from 1.5 to 3.3 eV, allowing both product kinetic energy distributions and angular distributions to be obtained from the data. The charge transfer process appears to be direct, dominated by long-range electron transfer that results in minimal deflection of the products. The product kinetic energy distributions are consistent with a process dominated by energy resonance. The kinetic energy distributions for C-N bond formation appear to scale with the total available energy, providing strong evidence that energy in the [CNH(3)](+) precursor to products is distributed statistically. The angular distributions for C-N bond formation show pronounced forward-backward symmetry, as expected for a complex that resembles a prolate symmetric top decaying along its symmetry axis.


A temporal examination of inspiratory muscle strength and endurance in hospitalized COVID-19 patients.
The two most common symptoms associated with COVID-19 are dyspnea and fatigue. One possible cause of such symptoms may be inspiratory muscle weakness. The purpose of this study was to examine inspiratory muscle performance (IMP) from intensive care unit discharge (ICUD) to hospital discharge (HD) in patients with COVID-19 hypothesizing that IMP would be markedly depressed at both ICUD and HD. IMP was examined at ICUD and HD via the PrO2 device (PrO2 Health, Smithfield, RI) which provided the maximal inspiratory pressure (MIP), sustained MIP (SMIP), inspiratory duration (ID), and fatigue index test (FIT). Patient symptoms were assessed at ICUD, HD, and 1-month post-HD. 30 patients (19 men, 11 women) with COVID-19 were included. The mean±SD age, BMI, and length of ICU and hospital stay was 71±11 yrs, 27.9 ± 6.3 kg/m, 9 ± 6 days, and 26±16 days, respectively. The mean±SD MIP, SMIP, ID, and FIT of the entire cohort at ICUD vs HD were 36±21 vs 40±20 cm H2O, 231±157 vs 297±182 PTU, 8.8 ± 4.2 vs 9.5 ± 4.6 s, and 9.0 ± 9.4 vs 13.1 ± 12.3, respectively, with only SMIP and FIT significantly greater at HD (p=.006 and 0.03, respectively). SMIP at HD was significantly related to resting dyspnea at HD (r=-0.40; p=.02). The SMIP and FIT of men were found to increase significantly from ICUD to HD, but no measure of IMP in the women increased significantly from ICUD to HD. At least one COVID-19-related symptom was present 1 month after HD with the most persistent symptoms being fatigue, cough, and dyspnea in 47%, 40%, and 37% of the patients, respectively. A significant reduction in IMP exists in patients with COVID-19 at both ICUD and HD and no measure of IMP in women was observed to increase significantly from ICUD to HD. Impaired inspiratory muscle endurance rather than strength was associated with greater dyspnea at HD.


Hippocampal volumetry for lateralization of temporal lobe epilepsy: automated versus manual methods.
The hippocampus has been the primary region of interest in the preoperative imaging investigations of mesial temporal lobe epilepsy (mTLE). Hippocampal imaging and electroencephalographic features may be sufficient in several cases to declare the epileptogenic focus. In particular, hippocampal atrophy, as appreciated on T1-weighted (T1W) magnetic resonance (MR) images, may suggest a mesial temporal sclerosis. Qualitative visual assessment of hippocampal volume, however, is influenced by head position in the magnet and the amount of atrophy in different parts of the hippocampus. An entropy-based segmentation algorithm for subcortical brain structures (LocalInfo) was developed and supplemented by both a new multiple atlas strategy and a free-form deformation step to capture structural variability. Manually segmented T1-weighted magnetic resonance (MR) images of 10 non-epileptic subjects were used as atlases for the proposed automatic segmentation protocol which was applied to a cohort of 46 mTLE patients. The segmentation and lateralization accuracies of the proposed technique were compared with those of two other available programs, HAMMER and FreeSurfer, in addition to the manual method. The Dice coefficient for the proposed method was 11% (p<10(-5)) and 14% (p<10(-4)) higher in comparison with the HAMMER and FreeSurfer, respectively. Mean and Hausdorff distances in the proposed method were also 14% (p<0.2) and 26% (p<10(-3)) lower in comparison with HAMMER and 8% (p<0.8) and 48% (p<10(-5)) lower in comparison with FreeSurfer, respectively. LocalInfo proved to have higher concordance (87%) with the manual segmentation method than either HAMMER (85%) or FreeSurfer (83%). The accuracy of lateralization by volumetry in this study with LocalInfo was 74% compared to 78% with the manual segmentation method. LocalInfo yields a closer approximation to that of manual segmentation and may therefore prove to be more reliable than currently published automatic segmentation algorithms.


Ultrafast dynamics of strongly correlated fermions-nonequilibrium Green functions and selfenergy approximations.
This article presents an overview on recent progress in the theory of nonequilibrium Green functions (NEGF). We discuss applications of NEGF simulations to describe the femtosecond dynamics of various finite fermionic systems following an excitation out of equilibrium. This includes the expansion dynamics of ultracold atoms in optical lattices following a confinement quench and the excitation of strongly correlated electrons in a solid by the impact of a charged particle. NEGF, presently, are the only ab initio quantum approach that is able to study the dynamics of correlations for long times in two and three dimensions. However, until recently, NEGF simulations have mostly been performed with rather simple selfenergy approximations such as the second-order Born approximation (SOA). While they correctly capture the qualitative trends of the relaxation towards equilibrium, the reliability and accuracy of these NEGF simulations has remained open, for a long time. Here we report on recent tests of NEGF simulations for finite lattice systems against exact-diagonalization and density-matrix-renormalization-group benchmark data. The results confirm the high accuracy and predictive capability of NEGF simulations-provided selfenergies are used that go beyond the SOA and adequately include strong correlation and dynamical-screening effects. With an extended arsenal of selfenergies that can be used effectively, the NEGF approach has the potential of becoming a powerful simulation tool with broad areas of new applications including strongly correlated solids and ultracold atoms. The present review aims at making such applications possible. To this end we present a selfcontained introduction to the theory of NEGF and give an overview on recent numerical applications to compute the ultrafast relaxation dynamics of correlated fermions. In the second part we give a detailed introduction to selfenergies beyond the SOA. Important examples are the third-order approximation, the [Formula: see text] approximation, the T-matrix approximation and the fluctuating-exchange approximation. We give a comprehensive summary of the explicit selfenergy expressions for a variety of systems of practical relevance, starting from the most general expressions (general basis) and the Feynman diagrams, and including also the important cases of diagonal basis sets, the Hubbard model and the differences occuring for bosons and fermions. With these details, and information on the computational effort and scaling with the basis size and propagation duration, readers will be able to choose the proper basis set and straightforwardly implement and apply advanced selfenergy approximations to a broad class of systems.


Aortic root bentall graft disarticulation following repair of type a aortic dissection.
A 47-year-old man presented with chest pain and was found to have an ascending aortic dissection. He underwent aortic arch resection and replacement with a hemishield tube graft with a valve conduit, better known as the Bentall technique. Five months later he presented with shortness of breath. A transesophageal echocardiogram revealed near-complete dehiscence of the mechanical valve conduit and a periaortic root abscess. He underwent removal of the conduit and placement of a homograft aortic root and valve. One month later he developed rigors. A transthoracic echocardiogram showed worsening systolic function and a periaortic hematoma or abscess. Serial transthoracic echocardiograms revealed increasing size in the periaortic echogenic free space and subsequent evidence of flow from the left ventricle into the periaortic space. He was determined not to be a surgical candidate and discharged to hospice in fair condition. He subsequently expired.


Isolation and characterization of an Escherichia coli strain with a high frequency of C-to-T mutations at 5-methylcytosines.
We used a genetic selection system to isolate a strain of Escherichia coli with a high frequency of C-to-T transition mutations at the second C of the sequence CCAGG. Cytosines in other sequences do not mutate to thymine at a high frequency in this strain, and the frequencies of other base substitution mutations are not increased to the same extent. The gene responsible for the mutator phenotype has been mapped to 43 min on the E. coli chromosome. Several lines of evidence indicate that this gene is distinct from the very short patch repair gene vsr.


Role of organic cation transporters in dopamine uptake across olfactory and nasal respiratory tissues.
Dopamine has poor oral bioavailability and low permeability across the blood-brain barrier, and yet it has been reported to have good systemic and central nervous system (CNS) bioavailability following nasal administration. The aim of this study was to investigate the extent to which dopamine transport in the olfactory and respiratory mucosae results from the activity of organic cation transporters (OCTs) present in the nasal cavity. Transport studies were carried out to determine the mechanism of dopamine transport across bovine olfactory and nasal respiratory mucosa. Western blotting and immunohistochemistry were performed to determine the expression and localization of organic cation transporter-2, a major transporter of dopamine, in the nasal mucosa. Dopamine transport was found to be saturable across both tissues. Amantadine, an organic cation transporter-1 (OCT-1) and organic cation transporter-2 (OCT-2) mixed inhibitor, decreased dopamine flux to a greater extent than guanidine, a more specific organic cation transporter-2 inhibitor. Immunohistochemistry results showed that organic cation transporter-2 was localized in both the epithelial and submucosal regions of the nasal olfactory and respiratory mucosa. Dopamine transport across the olfactory and respiratory mucosae is partially mediated by organic cation transporters, including OCT-1 and OCT-2. Utilization of uptake transporters may provide the opportunity for improved systemic absorption and targeted CNS delivery of dopamine and other drug compounds following nasal administration.


Studies on taste: molecular biology and food science.
Taste is indispensable for vertebrate to find a proper way of living by selection of foods at their discretion. It is also a mainstay in the construction of human culture and the food industry, but no systematic information is available regarding the molecular logic of taste signaling and associated chemical entities. Against this backdrop, our research had bumble beginnings in the 1990s and then traced a unique path of development revealing major signaling pathways involving G protein-coupled receptors, Galphai2, PLC-beta2, IP(3)R3, PLA2IIa, TRPM5, KCNQ1, etc. The validity of our studies on the molecular biology of taste was verified by material science in the case of an enigmatic protein, neoculin, which converts sourness to sweetness. The study should provide new information for better understanding of taste-taste interactions which are important in food design.


A flowcytometric analysis to efficiently quantify multiple innate immune cells and T Cell subsets in human blood.
The balance of inflammation and immunosuppression driven by changed ratios in diverse myeloid and T cell subsets, as well as their state of activation and ability to migrate to lymphoid compartments or inflammatory sites, has emerged as a highly active area of study across clinical trials of vaccines and therapies against cancer, trauma, as well as autoimmune and infectious diseases. There is a need for effective protocols which maximally use the possibilities offered by modern flow cytometers to characterize such immune cell changes in peripheral blood using small volumes of human blood. Additionally, longitudinal clinical studies often use cryopreserved samples, which can impact flow cytometric results. To efficiently gauge both the innate and the adaptive immune response, two novel 15-color antibody panels to identify key myeloid and T cell subsets and their functional potential were established. This approach was used to compare cellular immune profiles in fresh whole blood and in matched cryopreserved peripheral blood mononuclear cells (PBMCs). Cocktail I was designed to identify and characterize myeloid cell populations including dendritic cells (DCs), monocytic monocyte-derived suppressor cells (MO-MDSC), and monocytes, determining further core aspects of their state of maturity, T cell stimulatory (or inhibitory) potential, and migration capability. Cocktail II was used for phenotyping diverse T cells subsets, and their key migration and functional regulatory capabilities. The two 15-color antibody panels for the evaluation of both immune-stimulating and immunosuppressive processes presented herein allowed for efficient evaluation of the balance of immune activation versus immunosuppression across key blood cells, with good resolution for all 15 markers stained for in each panel. Gating strategies for the myeloid and T cells are presented to further support specific subset identification. This protocol was shown to be reproducible across donors and useful to study both RBC-lysed whole blood and cryopreserved PBMCs. © 2017 International Society for Advancement of Cytometry.


Interaction of MAP kinase with MAP kinase kinase: its possible role in the control of nucleocytoplasmic transport of MAP kinase.
The mitogen-activated protein kinase (MAPK) cascade consisting of MAPK and its direct activator, MAPK kinase (MAPKK), is essential for signaling of various extracellular stimuli to the nucleus. Upon stimulation, MAPK is translocated to the nucleus, whereas MAPKK stays in the cytoplasm. It has been shown recently that the cytoplasmic localization of MAPKK is determined by its nuclear export signal (NES) in the near N-terminal region (residues 33-44). However, the mechanism determining the subcellular distribution of MAPK has been poorly understood. Here, we show that introduction of v-Ras, active STE11 or constitutively active MAPKK can induce nuclear translocation of MAPK in mammalian cultured cells. Furthermore, we show evidence suggesting that MAPK is localized to the cytoplasm through its specific association with MAPKK and that nuclear accumulation of MAPK is accompanied by dissociation of a complex between MAPK and MAPKK following activation of the MAPK pathway. We have identified the MAPK-binding site of MAPKK as its N-terminal residues 1-32. Moreover, a peptide encompassing the MAPK-binding site and the NES sequence of MAPKK has been shown to be sufficient to retain MAPK to the cytoplasm. These findings reveal the molecular basis regulating subcellular distribution of MAPK, and identify a novel function of MAPKK as a cytoplasmic anchoring protein for MAPK.


Inertial effects in the nonlinear transient relaxation of rigid rodlike molecules in a strong dc electric field.
A method of calculation of nonlinear transient responses of an assembly of noninteracting polar linear molecules due to sudden changes in a strong external dc electric field is presented. The infinite hierarchy of differential-recurrence relations for the decay functions describing the relaxation of the system is derived by averaging the underlying inertial Langevin equation. The solution of this hierarchy is obtained in terms of matrix continued fractions. The integral relaxation time and the spectrum of the electric polarization for various nonlinear transient responses (step-on, step-off, and rapidly rotating field) are calculated for typical values of the model parameters. The nonlinear transient responses exhibit pronounced nonlinear effects due to the strong dc field. Analytical equations for the quantities of interest are presented in the overdamped limit. Furthermore, the linear response relaxation function and linear dynamic susceptibility are obtained as a particular case of a general nonlinear theory.


Genetic studies of coliphage P1. I. Mapping by use of prophage deletions.
One hundred and ten amber mutants of coliphage P1 were isolated and localized into groups with respect to the existing genetic map by use of nonpermissive Escherichia coli K-12 strains lysogenic for P1 with deletions. These lysogens contain one of three types of deletion prophages: P1cry and its derivatives, P1dlacs, and P1dpros. Fourteen such lysogens were tested for their ability to rescue the amber mutants which were then assigned to one of nine deletion segments of the P1 genome defined by the termini of the various prophage deletions. The relationship of the nine deletion segments with the published P1 map is described, two new segments having been added. The deletions of the 14 prophages overlapped sufficiently to indicate that the P1 genetic prophage map should be represented in circular form, which is consistent with the fact that P1 is normally a circular plasmid in the prophage state. The distribution of mutants into deletion segments is nonrandom for at least one segment. In addition, the deletion termini of the 14 defective prophages coincided in five out of nine regions separating the nine deletion segments. Various possible explanations are discussed for the nonrandom recurrence of these deletion termini, including the evidence of hot spots of recombination.


Efficacy of bisphosphonates and other bone-targeted agents in metastatic bone disease from solid tumors other than breast and prostate cancers.
Metastatic bone disease complicates the course of malignancy in a substantial proportion of patients with advanced cancer. Bisphosphonates are now widely used to improve skeleton-related outcomes of patients with metastatic cancer to the bone. Most studies evaluating the efficacy of bisphosphonates and other bone-targeted agents have been performed in patients with metastatic breast and prostate cancer. Only a few studies have evaluated the role of bisphosphonates in other tumor types involving the skeletal system. We present a review of the clinical literature focusing on the current and potential roles of bisphosphonates (particularly zoledronic acid) and newer bone-targeted therapies in patients with metastasis to bone arising from solid tumors other than breast and prostate cancer.


Curious bivalves: Systematic utility and unusual properties of anomalodesmatan mitochondrial genomes.
Mitogenomic trees for Bivalvia have proved problematic in the past, but several highly divergent lineages were missing from these analyses and increased representation of these groups may yet improve resolution. Here, we add seven new sequences from the Anomalodesmata and one unidentified semelid species (Bryopa lata, Euciroa cf. queenslandica, Laternula elliptica, Laternula truncata, Lyonsia norwegica, Myadora brevis, Tropidomya abbreviata, "Abra" sp.). We show that relationships in a mitogenomic tree for the Class are improved by the addition of seven anomalodesmatans from this highly divergent clade, but are still not completely consistent with relationships recovered in studies of nuclear genes. We suggest that some anomalous relationships (for instance the non-monophyly of Bivalvia) may be partially explained by compositional heterogeneity in the mitogenome and suggest that the addition of more taxa may help resolve both this effect and possible instances of long branch attraction. We also identify several curious features about anomalodesmatan mitogenomes. For example, many protein-coding gene boundaries are poorly defined in marine bivalves, but particularly so in anomalodesmatans, primarily due to non-conserved boundary sequences. The use of transcriptomic and genomic data together enabled better definition of gene boundaries, the identification of possible pseudogenes and suggests that most genes are translated monocistronically, which contrasts with many other studies. We also identified a possible case of gene duplication of ND5 in Myadora brevis (Myochamidae). Mitogenome size in the Anomalodesmata ranges from very small compact molecules, with the smallest for Laternula elliptica (Laternulidae) only 14,622bp, to Bryopa lata (Clavagellidae) which is at least 31,969bp long and may be >40,000bp. Finally, sampled species show a high degree of sequence divergence and variable gene order, although intraspecific variation in Laternula elliptica is very low.


[The importance of family in drug abuse treatment: a literature review].
This article presents a literature review on family and two phases of drug addiction treatment: engagement and treatment itself. Referring to various studies, the article highlights the need for addicts to be treated together with their families in order to achieve satisfactory results. The study points to important socio-cultural issues that influence institutional treatment and emphasizes that treatment of addicts and their families fosters an understanding and basis for effective preventive action.


Polymorphism in Adiponectin and Adiponectin Receptor Genes in Diabetes Mellitus Pathogenesis.
The role played by hereditary factors in the development of diabetes mellitus type 2 (DM2) has not yet been fully established. Therefore, the purpose of our study was to investigate the prevalence of adiponectin and polymorphism in its gene receptors in connection with the primary symptoms of DM2 pathogenesis. Genomic DNA was isolated from the whole blood of 94 patients with an established diagnosis of DM2 using the phenol-chloroform method. Gene polymorphisms were determined using real-time polymerase chain reaction (PCR). The most common polymorphic variants in patients with DM2 were the genotypes AA (rs11061971) and GG (rs16928751) on the ADIPOR2 gene. A strong correlation was found between the rs16928751 polymorphism on the ADIPOR2 gene and increased body mass index (BMI). TG (rs2275737) ADIPOR1 gene genotype carriers were found to have the highest levels of glycosylated hemoglobin (HbA1), whereas TT (rs2275738) caused stable hyperglycemia. In addition, the rs16928751 ADIPOR2 gene polymorphism showed an association with the development of key mechanisms of DM2 in the Russian population, although a number of genomic searches failed to show any association of this gene with DM2. Unique gene variants associated with the risk of developing DM2 in the Crimean population were established.


Transmeatal low-power laser irradiation for tinnitus.
To evaluate effectiveness of 60-mW laser irradiation in the treatment of tinnitus. Prospective, randomized double-blind study. This investigation included 68 ears in 45 patients with disabling unilateral or bilateral tinnitus. The active or placebo laser treatment was administered transmeatally once a week for 6 minutes. Laser irradiation was performed four times during a 4-week period. A questionnaire was administered to evaluate the loudness, duration, quality, and annoyance of tinnitus before and after irradiation. The loudness and pitch match for tinnitus were obtained, and distortion product otoacoustic emissions were also examined. No significant difference was observed between the active and placebo laser groups with regard to outcome of loudness, duration, quality, and annoyance of tinnitus. In one patient who received active laser treatment, acute hearing deterioration occurred after the third irradiation. Transmeatal low-power laser irradiation with 60 mW is not effective for the treatment of tinnitus.


Localization of ANP-synthesizing cells in rat stomach.
To study the morphological positive expression of antrial natriuretic peptide (ANP)-synthesizing cells and ultrastructural localization and the relationship between ANP-synthesizing cells and microvessel density in the stomach of rats and to analyze the distribution of the three histologically distinct regions of ANP-synthesizing cells. Using immunohistochemical techniques, we studied positive expression of ANP-synthesizing cells in rat stomach. A postembedding immunogold microscopy technique was used for ultrastructural localization of ANP-synthesizing cells. Microvessel density in the rat stomach was estimated using tannic acid-ferric chloride (TAFC) method staining. Distribution of ANP-synthesizing cells were studied in different regions of rat stomach histochemically. Positive expression of ANP-synthesizing cells were localized in the gastric mucosa of rats. Localization of ANP-synthesizing cells identified them to be enterochrochromaffin cells (EC) by using a postembedding immunogold electron microscopy technique. EC cells were in the basal third of the cardiac mucosa region. ANP-synthesizing cells existed in different regions of rat stomach and its density was largest in the gastric cardiac region, and the distribution order of ANP-synthesizing cells in density was cardiac region, pyloric region and fundic region in mucosa layer. We have also found a close relationship between ANP-synthesizing cells and microvessel density in gastric mucosa of rats using TAFC staining. ANP-synthesizing cells are expressed in the gastric mucosa. EC synthesize ANP. There is a close relationship between ANP-synthesizing cells and microvessel density in gastric mucosa of rats. The distribution density of ANP-synthesizing cells is largest in the gastric cardiac region.


Mitochondria are the main target for oxidative damage in leaves of wheat (Triticum aestivum L.).
Photosynthesis, respiration, and other processes produce reactive oxygen species (ROS) that can cause oxidative modifications to proteins, lipids, and DNA. The production of ROS increases under stress conditions, causing oxidative damage and impairment of normal metabolism. In this work, oxidative damage to various subcellular compartments (i.e. chloroplasts, mitochondria, and peroxisomes) was studied in two cultivars of wheat differing in ascorbic acid content, and growing under good irrigation or drought. In well-watered plants, mitochondria contained 9-28-fold higher concentrations of oxidatively modified proteins than chloroplasts or peroxisomes. In general, oxidative damage to proteins was more intense in the cultivar with the lower content of ascorbic acid, particularly in the chloroplast stroma. Water stress caused a marked increase in oxidative damage to proteins, particularly in mitochondria and peroxisomes. These results indicate that mitochondria are the main target for oxidative damage to proteins under well-irrigated and drought conditions.


Marker Pen Device with Concentration Gradient Nib for Antibiotic Susceptibility Testing.
Pen-based devices have emerged as useful tools for measuring pH and glucose, and for fabricating microchannels and microarrays. Pen-based devices take advantage of flexible patterning, inexpensive costs, and small volumes, thereby saving time and increasing efficiency. We have developed a gradient nib marker pen device that generated simultaneously different antibiotic concentrations in bacteria antibiotic susceptibility testing (AST). The device can deposit on the target surface with the antibiotic gradient. The designed polyester fiber nibs are a highly uniform porosity with unidirectional orientation and produce a visible gradient pattern. We have demonstrated and quantitatively analyzed bacterial growth after antibiotic marking. The antibiotic marking produces an inhibition zone of bacterial growth. The inhibition zones of bacterial growth are captured and converted to 8-bit grayscale images, and then quantified by gray values using the Image J program. A profile of the inhibition zone showed different gray values in response to bacterial viability. The gradient nib marker pen device can be used to determine the quantitative antibiotic concentration based on the relationship between gray values and bacterial density conveniently without requiring a series of dilution tubes, including nutrient medium, and diversely diluted antibiotics.


High-Pressure Synthesis of Molybdates with the Wolframite Structure.
A series of small cation molybdates, MgMoO(4), MnMoO(4), FeMoO(4), CoMoO(4), NiMoO(4), and ZnMoO(4) with the wolframite structure characteristic of the corresponding tungstates have been synthesized at high pressure and temperature. The high-pressure compounds revert to the ambient pressure modifications if heated in air at 600 degrees C.


Changing Urban Carbon Metabolism over Time: Historical Trajectory and Future Pathway.
Cities are expected to play a major role in carbon emissions mitigation. A key step in decoupling urban economy from carbon emissions is to understand the full impact of socioeconomic development on urban metabolism over time. Herein, we establish a system-based framework for modeling the variation of urban carbon metabolism through time by integrating a metabolic flow inventory, input-output model, and network analysis. Using Beijing as a case study, we track the historical trajectory of carbon flows embodied in urban final consumption over 1985-2012. We find that while the tendency of increase in direct carbon emission continues within this time frame, consumption-based carbon footprint might have peaked around 2010. Significant transitions in emission intensity and roles sectors play in transferring carbon over the period are important signs of decoupling urban development from carbonization. Our further analysis of driving factors reveals a strong competition between efficiency gains and consumption level rise, showing a cumulative contribution of -584% and 494% to total carbon footprint, respectively. Projection into a future pathway suggests there is still a great potential for carbon mitigation for the city, but a strong mitigation plan is required to achieve such decarbonization before 2030. By bridging temporal metabolic model and socioeconomic planning, this framework fills one of the main gaps between monitoring of urban metabolism and design of a low-carbon economy.


Design of low polarization off-axis three-mirror reflective optical systems.
Off-axis optical systems have several important advantages over on-axis ones. However, high polarization aberrations, which play important roles in many applications, become critical disadvantages of off-axis systems. Thanks to the seven free design parameters, three-mirror reflective systems have a good potential to achieve low polarization. A general method to design low polarization off-axis three-mirror reflective optical systems is proposed in this paper. Based on genetic algorithms, several off-axis three-mirror systems with both low polarization aberrations and good wave aberrations are designed. The method proposed in this paper is versatile and can be used to design other types of optical systems that demand low polarization aberrations.


Using technology to overcome the language barrier: the Cognitive Assessment for Aphasia App.
We developed and explored the feasibility and user acceptance of the Cognitive Assessment for Aphasia App: a non-immersive virtual reality cognitive assessment for stroke survivors, designed to be inclusive of individuals with aphasia. Participants were assessed on a battery of pen-and-paper cognitive tests and the Cognitive Assessment for Aphasia App. Feasibility was explored by quantifying missing data for test completion, determining user acceptance for the app by measuring participants' preferred testing method, enjoyment and perceived task difficulty and time-taken to complete the test. Sixty-four stroke participants (35 with aphasia, 29 without aphasia) and 32 controls were recruited. Only one participant with aphasia was unable to complete all the Cognitive Assessment for Aphasia App tasks, whereas 13 participants were unable to complete all pen-and-paper tasks. Only 14% of participants preferred the pen-and-paper tests, and preference did not significantly differ between groups. Ninety-five per cent of participants were neutral or enjoyed the app and 4% perceived it to be very difficult. Higher age was negatively associated with user acceptance measures. The study shows preliminary evidence for the Cognitive Assessment for Aphasia App to be a feasible cognitive assessment for stroke survivors with and without aphasia. The app is currently being validated in stroke. Implications for rehabilitation The Cognitive Assessment for Aphasia App is a feasible tool for assessing post-stroke cognition in acute, inpatient rehabilitation and community settings. In research trials examining cognition, individuals with aphasia are often excluded. The Cognitive Assessment for Aphasia App permits the inclusion of these individuals, enhancing generalizability. The Cognitive Assessment for Aphasia App provides an alternative method to assess cognition that is quicker and preferred over standard neuropsychological tests.


Effect of lower limb exercise on forearm vascular function: contribution of nitric oxide.
We examined vascular function in an inactive muscle bed, the forearm, during lower limb exercise and determined the contribution of endothelium-derived nitric oxide (NO) to the hyperemic response. Eight young males were randomized to participate in two studies, each consisting of two bouts of lower limb exercise, separated by a 30-min recovery. Peak forearm blood flow (PFBF) and mean blood flow (MFBF) were continuously recorded at baseline and during exercise using continuous high-resolution vascular ultrasound and Doppler flow velocity measurement. During one session, the brachial artery was cannulated to allow continuous infusion of saline or N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthase. The alternate session was performed to control for possible effects of repeated exercise. At 60, 100, and 160 W, L-NMMA significantly decreased both PFBF and MFBF compared with the saline infusion. These results suggest that systemic production of NO occurs during exercise in resting vessel beds, which do not feed metabolically active tissue. This finding provides a plausible explanation for the antiatherogenic benefits of exercise.


Midtrimester pregnancy termination with prostaglandin E2 vaginal suppositories.
One hundred midtrimester pregnancies were randomly selected for elective termination with 20 mg prostaglandin E2 vaginal suppositories. The abortion rate was 93%. There were 66% complete abortions, 27% incomplete abortions and 7% failures. Mean insertion abortion time was 17 hours, 26 minutes. Average dosage was 82 mg. There were no mortalities but a high percentage of side effects, all of which were well tolerated. Two patients were admitted to other hospitals unfamiliar with termination technics, transfused and subjected to dilatations and curettages. There were no long-term sequelae.


The clinical application of ABCB1 genotyping in antidepressant treatment: a pilot study.
The gene product of the ABCB1 gene, the P-glycoprotein, functions as a custodian molecule in the blood-brain barrier and regulates the access of most antidepressants into the brain. Previous studies showed that ABCB1 polymorphisms predicted the response to antidepressants that are substrates of the P-gp, while the response to nonsubstrates was not influenced by ABCB1 polymorphisms. The aim of the present study was to evaluate the clinical application of ABCB1 genotyping in antidepressant pharmacotherapy. Data came from 58 depressed inpatients participating in the Munich Antidepressant Response Signature (MARS) project, whose ABCB1 gene test results were implemented into the clinical decision making process. Hamilton Depression Rating Scale (HAM-D) scores, remission rates, and duration of hospital stay were documented with dose and kind of antidepressant treatment. Patients who received ABCB1 genotyping had higher remission rates [χ2(1) = 6.596, p = 0.005, 1-sided] and lower Hamilton sores [t(111) = 2.091, p = 0.0195, 1-sided] at the time of discharge from hospital as compared to patients without ABCB1 testing. Among major allele homozygotes for ABCB1 single nucleotide polymorphisms (SNPs) rs2032583 and rs2235015 (TT/GG genotype), an increase in dose was associated with a shorter duration of hospital stay [rho(28) = -0.441, p = 0.009, 1-sided], whereas other treatment strategies (eg, switching to a nonsubstrate) showed no significant associations with better treatment outcome. Discussion The implementation of ABCB1 genotyping as a diagnostic tool influenced clinical decisions and led to an improvement of treatment outcome. Patients carrying the TT/GG genotype seemed to benefit from an increase in P-gp substrate dose. Results suggest that antidepressant treatment of depression can be optimized by the clinical application of ABCB1 genotyping.


Some evidence suggesting the existence of P2 and B3 sites in the active site of bovine pancreatic ribonuclease A.
In order to clarify the subsite structure of ribonuclease A (RNase A), the interactions of pdTp, pAp, dTpdAp, and pdTpdAp with RNase A were investigated by means of kinetic studies and 31P NMR spectroscopy. The pH profile of the 31P NMR spectrum of RNase A-pdTp complex indicated the interaction of the 3'- and 5'-phosphates with RNase A. The signal of 3'-phosphate of pdTp in the presence of RNase A gave a characteristic titration curve indicating the participation of more than 2 ionic groups in the P1 subsite. A similar 31P NMR titration was observed in the case of 5'-phosphate of pAp in the presence of RNase A. The results indicated that pAp interacted with RNase A at the P1, B2, and P2 sites. dTpdAp and pdTpdAp inhibited RNase A action more markedly than dTpdA, indicating the contribution of 3'- and 5'-terminal phosphate groups attached to dTpdA to the affinity of RNase A. The 31P NMR spectra of RNase A-dTpdAp and pdTpdAp complexes excluded the possible interaction of the monoester type phosphate of the inhibitors with the P1 site of RNase A, thus indicating the binding of the 3'-side phosphates with the P2 subsite of RNase A.


Flow cytometry and solid organ transplantation: a perfect match.
In the field of transplantation, flow cytometry serves a well-established role in pre-transplant crossmatching and monitoring immune reconstitution following hematopoietic stem cell transplantation. The capabilities of flow cytometers have continuously expanded and this combined with more detailed knowledge of the constituents of the immune system, their function and interaction and newly developed reagents to study these parameters have led to additional utility of flow cytometry-based analyses, particularly in the post-transplant setting. This review discusses the impact of flow cytometry on managing alloantigen reactions, monitoring opportunistic infections and graft rejection and gauging immunosuppression in the context of solid organ transplantation.


RNA recognition and stress granule formation by TIA proteins.
Stress granule (SG) formation is a primary mechanism through which gene expression is rapidly modulated when the eukaryotic cell undergoes cellular stresses (including heat, oxidative, viral infection, starvation). In particular, the sequestration of specifically targeted translationally stalled mRNAs into SGs limits the expression of a subset of genes, but allows the expression of heatshock proteins that have a protective effect in the cell. The importance of SGs is seen in several disease states in which SG function is disrupted. Fundamental to SG formation are the T cell restricted intracellular antigen (TIA) proteins (TIA-1 and TIA-1 related protein (TIAR)), that both directly bind to target RNA and self-associate to seed the formation of SGs. Here a summary is provided of the current understanding of the way in which TIA proteins target specific mRNA, and how TIA self-association is triggered under conditions of cellular stress.


Just say no to psychotropic drugs!
Prescribing drugs for mental disorders by psychologists means accepting an invalid model--the brain disease, biological-defect explanation of psychopathology--that is advanced by political conservatives and accepted by some naive, well-intentioned, but misinformed moderates who have not thought critically about the issue. Conservative psychiatry serves the ruling class by rejecting or ignoring the fact that most mental disorders are learned in the context of social and economic injustice, and familiar dysfunction. If we accept the fallacy of brain disease and genetic defect as the major causes of mental disorder and succeed in getting prescription privileges we will have sold our soul to the devil!


A clinical study on the expression of PTEN in renal cell carcinoma in children.
The expression pattern of tumor suppressor gene phosphatase and tensin homolog deleted on chromosome ten (PTEN) and phosphatase and tensin homolog deleted on chromosome ten/phosphatidylinositol3-kinase/protein kinase B (PTEN/PI3K/AKT) cell signaling pathway in renal cell carcinoma (RCC) were investigated in children. A total of 5 cases of RCC (observation group) in children and 10 cases of benign kidney tumor (control group) diagnosed by pathological examinations were included to obtain tumor samples. Expression of PTEN mRNA was detected by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). The protein expression of PTEN, PI3K and AKT was detected by western blotting; relationships between the expression level of PTEN mRNA and the clinical features of RCC were analyzed. It turned out that expression level of PTEN mRNA in the observation group was significantly lower than that in the control group. The protein expression levels of PTEN, PI3K and AKT were significantly lower in the observation group than in the control group (P<0.05). The expression level of PTEN mRNA decreased with the increased clinical stage of RCC (P<0.05), and was not related to sex, age and maximum tumor diameter (P>0.05). The results showed that downregulation of the tumor suppressor gene PTEN expression and the inhibition of PTEN/PI3K/AKT cell signaling pathway may be involved in the occurrence and development of RCC in children.


Bioecology and breeding performance of cattle egret (Bubulcus ibis) in selected sites at Sharkia Governorate, Egypt.
Cattle egret Bubulcus ibis, feeds on insect pests in many agro-ecosystems. Thus, there is an urgent need to study the breeding chronology of cattle egret, in order to develop suitable protection programs for this beneficial bird to perform its role as abiological control agent in Egyptian agro-ecosystems. The study was conducted at Sharkia Governorate, Egypt, from December 2018 to December 2020; in different habitats (irrigation canals, drainage canals, garbage collection areas and Abbasa ponds). The mean clutch size ranged from 2-5 eggs/nest with an incubation period ranging between 21-25 days. The mean percentage of hatching success was 90.21%, while the total number of mortality eggs was 47 and the total egg hatching was 433. Also the total number of nests located nearby tree trunks were 73, while nests located in the core of the tree were 47 nests, and nests located at the peripherals were 15 nests.


Patients With Epileptic Seizures and Multiple Sclerosis in a Multiple Sclerosis Center in Southern Germany Between 2003-2015.
Background: So far, many studies have shown that the risk of developing seizures and epilepsy is higher among patients with multiple sclerosis (MS) than in the general population. However, the causal link between these two diseases is still unclear. In addition, it is not clearly understood whether and to what extent the manifestation of seizures and epilepsy in patients with MS affects the clinical course and the long-term prognosis of the disease. We aimed to retrospectively identify and describe patients with MS and with seizures and epilepsy which were seen at the Department of Neurology of the University of Regensburg in Germany between the years 2003-2015. Methods: With the help of the electronic documentation system of hospital admitted patients followed by scrutinizing medical records of patients with MS for evidence of seizures and epilepsy, we identified patients with MS and seizures or epilepsy. Results: We identified 22 individuals (1.74%) out of 1,267 patients with MS with seizures or epilepsy. 18 of these 22 individuals met criteria for epilepsy (1.42%). Nine MS patients (40.9%) suffered from relapsing-remitting MS (RRMS) whereas 11 MS patients (50.0%) showed a secondary progressive disease course (SPMS). Five of those (45.5%) converted from RRMS to SPMS before they acquired epilepsy. None of the identified patients with MS and seizures or epilepsy suffered from primary progressive MS (PPMS). Moreover, two MS patients (9.1%) had a history of seizures before MS onset. Seizures were of focal onset in 17 patients with MS (77.3%). Fourteen out of these 17 MS patients presented with focal to bilateral tonic-clonic seizures (82.4%). Five MS patients (22.7%) showed tonic clonic seizures of unknown onset. Status epilepticus was reported in three patients with MS (13%), for one patient the data was inconclusive. Conclusion: The occurrence of seizures and epilepsy was higher than in the general population, suggesting a causal relationship between both diseases. In most cases, seizures occurred after the first manifestation of MS. The high frequency of focal seizures supports the concept of cerebral lesions in patients with MS playing an important role in precipitation of seizures and epilepsy.


Studying multisite binary and ternary protein interactions by global analysis of isothermal titration calorimetry data in SEDPHAT: application to adaptor protein complexes in cell signaling.
Multisite interactions and the formation of ternary or higher-order protein complexes are ubiquitous features of protein interactions. Cooperativity between different ligands is a hallmark for information transfer, and is frequently critical for the biological function. We describe a new computational platform for the global analysis of isothermal titration calorimetry (ITC) data for the study of binary and ternary multisite interactions, implemented as part of the public domain multimethod analysis software SEDPHAT. The global analysis of titrations performed in different orientations was explored, and the potential for unraveling cooperativity parameters in multisite interactions was assessed in theory and experiment. To demonstrate the practical potential and limitations of global analyses of ITC titrations for the study of cooperative multiprotein interactions, we have examined the interactions of three proteins that are critical for signal transduction after T-cell activation, LAT, Grb2, and Sos1. We have shown previously that multivalent interactions between these three molecules promote the assembly of large multiprotein complexes important for T-cell receptor activation. By global analysis of the heats of binding observed in sets of ITC injections in different orientations, which allowed us to follow the formation of binary and ternary complexes, we observed negative and positive cooperativity that may be important to control the pathway of assembly and disassembly of adaptor protein particles.


Multifocal septic arthritis, gluteal abscess and spondylodiscitis by Streptococcus dysgalactiae subspecies equisimilis after an intramuscular injection.
We present the case of a 63-year-old man, admitted for hand cellulitis and acute kidney injury. A Streptococcus dysgalactiae subsp equisimilis (SDSE) was isolated in blood cultures and despite directed intravenous antibiotherapy, the patient evolved unfavourably, with dorsolumbar spondylodiscitis, multifocal septic arthritis and abscesses. CT also showed densification of the gluteal muscles, multiple air bubbles in the psoas, paraspinal muscles and spinal canal that were associated with an intramuscular injection administered 1 week earlier for a backache. After escalation of the antibiotherapy and intensive supportive measures, the patient showed improvement and was discharged after 8 weeks of antibiotherapy.The incidence of invasive SDSE infections has been growing, especially in immunosupressed patients. In this case, despite no predisposing factor identified, it evolved to severe sepsis. The intramuscular injection, a trivialised but not harmless procedure, was the assumed port of entry, as previously described in another case report.


Detection of nucleoside triphosphate hydrolase as a circulating antigen in sera of mice infected with Toxoplasma gondii.
The nucleoside triphosphate hydrolase, which is present in the tachyzoite form of Toxoplasma gondii, was detected as a circulating antigen in sera of mice infected with a virulent (RH) or an avirulent (Beverly) strain of T. gondii. The enzyme was detected with a monoclonal antibody incorporated into an enzyme-linked immunosorbent assay. The lower limit of sensitivity of the assay was about 0.3 ng/ml, and standard assays provided a linear plot of nucleoside triphosphate hydrolase concentration over a range of 0.3 to 12 ng/ml. In mice inoculated intraperitoneally with tachyzoites of the RH strain, nucleoside triphosphate hydrolase emerged in the serum 1 day after injection, and then the concentration increased and reached a value of 30 micrograms/ml on day 5. In mice inoculated intraperitoneally with cysts of the Beverly strain, nucleoside triphosphate hydrolase was detected at day 3 after injection, and a peak concentration of 89 ng/ml was seen on day 10. The concentration of enzyme decreased thereafter, and the enzyme disappeared from the circulation on day 56.


A method to evaluate contractures effects during the gait of children with Duchenne dystrophy.
Joint contractures are the second major impairment affecting the locomotor system of children with Duchenne muscular dystrophy (DMD). While the negative influence of joint contractures has been documented, the passive moments produced by joint contractures could benefit the gait of patients with muscle weakness. We describe a biomechanical model that quantifies the mechanical contribution of ankle and hip flexion contractures to the gait of DMD children. Kinematic and kinetic parameters were measured under the same experimental conditions during the gait and passive resistance assessment of two subjects: one healthy child as a control, and one child with DMD. The child with DMD had a plantar flexion contracture and a greater ankle stiffness coefficient than the control child. During gait, the contribution of the ankle passive moment to the net moment was more important for the child with DMD than for the control child. At the hip, passive joint moments and passive moment contribution were more important for the control child but this was not related to the presence of hip flexion contracture. These preliminary results suggest the model might be used to evaluate contractures effect on a larger cohort of subjects.


Effects of the nucleoid protein HU on the structure, flexibility, and ring-closure properties of DNA deduced from Monte Carlo simulations.
The histone-like HU (heat unstable) protein plays a key role in the organization and regulation of the Escherichia coli genome. The nonspecific nature of HU binding to DNA complicates analysis of the mechanism by which the protein contributes to the looping of DNA. Conventional models of the looping of HU-bound duplexes attribute the changes in biophysical properties of DNA brought about by the random binding of protein to changes in the effective parameters of an ideal helical wormlike chain. Here, we introduce a novel Monte Carlo approach to study the effects of nonspecific HU binding on the configurational properties of DNA directly. We randomly decorated segments of an ideal double-helical DNA with HU molecules that induce the bends and other structural distortions of the double helix find in currently available X-ray structures. We find that the presence of HU at levels approximating those found in the cell reduces the persistence length by roughly threefold compared with that of naked DNA. The binding of protein has particularly striking effects on the cyclization properties of short duplexes, altering the dependence of ring closure on chain length in a way that cannot be mimicked by a simple wormlike model and accumulating at higher-than-expected levels on successfully closed chains. Moreover, the uptake of protein on small minicircles depends on chain length, taking advantage of the HU-induced deformations of DNA structure to facilitate ligation. Circular duplexes with bound HU show much greater propensity than protein-free DNA to exist as negatively supercoiled topoisomers, suggesting a potential role of HU in organizing the bacterial nucleoid. The local bending and undertwisting of DNA by HU, in combination with the number of bound proteins, provide a structural rationale for the condensation of DNA and the observed expression levels of reporter genes in vivo.


Alternative Visions for Pastoral Work with LGBTQ Individuals, Families, and Communities: A Response.
Multiple theological perspectives provide frameworks for pastoral work with lesbian, gay, bisesxual and trans individuals, families, and communities. One model is offered by those who argue for celibacy or heterosexual marriages for those who self-identify as part of LGBTQ communities. This article names other theologically grounded perspectives with the goal of inviting practitioners to broaden their understandings and wrestle with the implications of their theological and ethical stances. When reflecting on the intersection of spirituality and sexuality, the meaning of theological terms such as sin, contributions from queer theologians and pastoral counselors, and the limitations of binary categories common in our theological history, this article encourages pastoral counselors and spiritual care providers to re-examine theological assumptions they bring to their work. The article ends with questions and opportunities for ongoing pastoral theological work and reflection.


SLAM-associated protein as a potential negative regulator in Trk signaling.
Neurotrophin signaling plays important roles in regulating the survival, differentiation, and maintenance of neurons in the nervous system. Binding of neurotrophins to their cognate receptors Trks induces transactivation and phosphorylation of the receptor at several tyrosine residues. These phosphorylated tyrosine residues then serve as crucial docking sites for adaptor proteins containing a Src homology 2 or phosphotyrosine binding domain, which upon association with the receptor initiates multiple signaling events to mediate the action of neurotrophins. Here we report the identification of a Src homology 2 domain-containing molecule, SLAM-associated protein (SAP), as an interacting protein of TrkB in a yeast two-hybrid screen. SAP was initially identified as an adaptor molecule in SLAM family receptor signaling for regulating interferon-gamma secretion. In the current study, we found that SAP interacted with TrkA, TrkB, and TrkC receptors in vitro and in vivo. Binding of SAP required Trk receptor activation and phosphorylation at the tyrosine 674 residue, which is located in the activation loop of the kinase domain. Overexpression of SAP with Trk attenuated tyrosine phosphorylation of the receptors and reduced the binding of SH2B and Shc to TrkB. Moreover, overexpression of SAP in PC12 cells suppressed the nerve growth factor-dependent activation of extracellular signal-regulated kinases 1/2 and phospholipase Cgamma, in addition to inhibiting neurite outgrowth. In summary, our findings demonstrated that SAP may serve as a negative regulator of Trk receptor activation and downstream signaling.


[Second national survey of intestinal parasitic infections in Cuba, 2009].
the intestinal parasitic infections are still endemic in Cuba, with a higher frequency in rural and mountain regions. Twenty five years after the last national survey, it deemed necessary to carry out a new national survey in order to know the prevalence of intestinal parasitic infections and to compare the obtained results between both studies. That knowledge would be valuable to work out strategies of health and to design a control program for intestinal parasitic infections in Cuba. to determine the current prevalence of intestinal parasitic infections in Cuba and to compare these results with those obtained from the previous survey after a 25 year-period. a cross sectional study was conducted from May to August of 2009 in a sample of Cuban population. A stool sample was collected from each individual, which was analyzed by direct examination, Willis' brine flotation method and the Kato-Katz thick smear technique. Additionally, a questionnaire was administered. the comparison between 1984 and 2009 surveys showed a general decrease of frequencies of intestinal parasitic infections caused by both helminths and pathogenic protozoa; however, the percentage of infections with commensal protozoa increased in 2009. In this last survey, there was observed decline of frequencies of infections with soil transmitted species, Trichuris trichiura, Ascaris lumbricoides, hookworm, and Strongyloides stercoralis and the pathogenic protozoa: Giardiau lamblia, Entamoeba histolytica/E. dispar, and the commensals: Endolimax nana and Entamoeba coli. The intestinal parasite Enterobius vermicularis was the only parasitic species that increased the frequency of infections with respect to the 1984 survey. The frequencies of parasitic and commensal infections in both studies were higher in the 5-14 y age group (school age). the comparison between the intestinal parasitic infections surveys of 1984 and 2009 showed a reduction in the frequencies of intestinal parasitic infections in the last survey. The finding in both studies of a higher frequency of pathogenic parasitic infections and commensal infections in the 5-14 y age group (school age) supports the recommendation of making emphasis on the control programs for intestinal parasitic infections in this age group.


Sex differences in long-term effects of collagen-induced arthritis in middle-aged mice.
Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disorder with high prevalence among middle-aged women. Collagen-induced arthritis (CIA) is the most widely used animal model of RA, however, sex differences and long-term effects of CIA in mice are poorly described in the literature. Aim: Therefore, the present study aimed to analyze the long-term effects of CIA on the joints of middle-aged mice of both sexes and to describe potential sex differences. Materials and methods: CIA was induced in middle-aged DBA/1J mice by immunization with bovine type II collagen and complete Freund's adjuvant. Saline was administered to control mice. Arthritis score assessment, plethysmometry, and thermal imaging of the joints were performed weekly for 15 weeks. Locomotor activity, micro-computed tomography, joint histology and biochemical analyses were performed at the end of the experiment. Results: Our results indicate a similar prevalence of arthritis in both sexes of mice-67% (8/12) of females and 89% (8/9) males with an earlier onset in males (day 14 vs. day 35). After the arthritis scores peaked on day 56 for males and day 63 for females, they steadily declined until the end of the experiment on day 105. A similar dynamics was observed in paw volume and temperature analyzing different aspects of joint inflammation. Long-term consequences including higher proteinuria (by 116%), loss of bone density (by 33.5%) and joint damage in terms of synovial hyperplasia as well as bone and cartilage erosions were more severe in CIA males compared to CIA females. There were no significant differences in locomotor activity between CIA mice and CTRL mice of any sex. Conclusion: This is the first study to describe the long-term effects of the CIA model in terms of sex differences in DBA/1J mice. Our results indicate sex differences in the dynamics, but not in the extent of arthritis. An earlier onset of arthritis and more severe consequences on joints, bones and kidneys were found in males. The underlying immune pathomechanisms responsible for the limited duration of the arthritis symptoms and the opposite sex difference in comparison to RA patients require further investigation.


Dependency of Tamoxifen Sensitive and Resistant ER+ Breast Cancer Cells on Semaphorin 3C (SEMA3C) for Growth.
Estrogen receptor positive (ER+) breast cancer (BCa) accounts for the highest proportion of breast cancer-related deaths. While endocrine therapy is highly effective for this subpopulation, endocrine resistance remains a major challenge and the identification of novel targets is urgently needed. Previously, we have shown that Semaphorin 3C (SEMA3C) is an autocrine growth factor that drives the growth and treatment resistance of various cancers, but its role in breast cancer progression and endocrine resistance is poorly understood. Here, we report that SEMA3C plays a role in maintaining the growth of ER+ BCa cells and is a novel, tractable therapeutic target for the treatment of ER+ BCa patients. Analyses of publicly available clinical datasets indicate that ER+ BCa patients express significantly higher levels of SEMA3C mRNA than other subtypes. Furthermore, SEMA3C mRNA expression was positively correlated with ESR1 mRNA expression. ER+ BCa cell lines (MCF7 and T47D) expressed higher levels of SEMA3C mRNA and protein than a normal mammary epithelial MCF10A cell line. ER siRNA knockdown was suppressed, while dose-dependent beta-estradiol treatment induced SEMA3C expression in both MCF7 and T47D cells, suggesting that SEMA3C is an ER-regulated gene. The stimulation of ER+ BCa cells with recombinant SEMA3C activated MAPK and AKT signaling in a dose-dependent manner. Conversely, SEMA3C silencing inhibited Estrogen Receptor (ER) expression, MAPK and AKT signaling pathways while simultaneously inducing apoptosis, as monitored by flow cytometry and Western blot analyses. SEMA3C silencing significantly inhibited the growth of ER+ BCa cells, implicating a growth dependency of ER+ BCa cells on SEMA3C. Moreover, the analysis of tamoxifen resistant (TamR) cell models (TamC3 and TamR3) showed that SEMA3C levels remain high despite treatment with tamoxifen. Tamoxifen-resistant cells remained dependent on SEMA3C for growth and survival. Treatment with B1SP Fc fusion protein, a SEMA3C pathway inhibitor, attenuated SEMA3C-induced signaling and growth across a panel of tamoxifen sensitive and resistant ER+ breast cancer cells. Furthermore, SEMA3C silencing and B1SP treatment were associated with decreased EGFR signaling in TamR cells. Here, our study implicates SEMA3C in a functional role in ER+ breast cancer signaling and growth that suggests ER+ BCa patients may benefit from SEMA3C-targeted therapy.


Development of a simultaneous Hugoniot and temperature measurement for preheated-metal shock experiments: melting temperatures of Ta at pressures of 100 GPa.
Equations of state of metals are important issues in earth science and planetary science. A major limitation of them is the lack of experimental data for determining pressure-volume and temperature of shocked metal simultaneously. By measuring them in a single experiment, a major source of systematic error is eliminated in determining from which shock pressure release pressure originates. Hence, a non-contact fast optical method was developed and demonstrated to simultaneously measure a Hugoniot pressure-volume (P(H)-V(H)) point and interfacial temperature T(R) on the release of Hugoniot pressure (P(R)) for preheated metals up to 1000 K. Experimental details in our investigation are (i) a Ni-Cr resistance coil field placed around the metal specimen to generate a controllable and stable heating source, (ii) a fiber-optic probe with an optical lens coupling system and optical pyrometer with ns time resolution to carry out non-contact fast optical measurements for determining P(H)-V(H) and T(R). The shock response of preheated tantalum (Ta) at 773 K was investigated in our work. Measured data for shock velocity versus particle velocity at an initial state of room temperature was in agreement with previous shock compression results, while the measured shock data between 248 and 307 GPa initially heated to 773 K were below the Hugoniot evaluation from its off-Hugoniot states. Obtained interfacial temperatures on release of Hugoniot pressures (100-170 GPa) were in agreement with shock-melting points at initial ambient condition and ab initio calculations of melting curve. It indicates a good consistency for shock melting data of Ta at different initial temperatures. Our combined diagnostics for Hugoniot and temperature provides an important approach for studying EOS and the temperature effect of shocked metals. In particular, our measured melting temperatures of Ta address the current controversy about the difference by more than a factor of 2 between the melting temperatures measured under shock and those measured in a laser-heated diamond anvil cell at ∼100 GPa.


Activation and partial proteolysis of variant glucocorticoid receptors, studied by two-phase partitioning.
In cultured lines of mouse lymphoma cells, resistant to glucocorticoids is frequently associated with the occurrence of glucocorticoid receptors with an abnormally low affinity (nt-) or an abnormally high affinity (nti) for nuclei and DNA. We have investigated whether the abnormal affinities for DNA are correlated with alterations in charge and surface properties of the receptors, that would be revealed through the partition coefficient in aqueous dextran/poly(ethylene glycol) two-phase systems. We have found that none of the receptor variants is defective in the activation step per se, and that only the nti receptors are abnormal in partition properties. Partial proteolysis of wild-type and nt- receptors with alpha-chymotrypsin produces forms which are indistinguishable from the nti receptors with respect to partition coefficients. Upon alpha-chymotrypsin treatment the wild-type receptors attain DNA-binding properties identical to those of the nti receptors, while the nt- receptors, in spite of some increase in DNA affinity, still bind less firmly to DNA than the alpha-chymotrypsin-treated wild-type receptors. alpha-Chymotrypsin treatment of the various receptor types also produces an increase in the binding to dextran sulphate, but the dextran sulphate affinity is higher and varies less between different receptor types than the DNA affinity. Trypsin-treated receptors were found to be devoid of affinity for DNA and dextran sulphate.


Stem cell signaling. An integral program for tissue renewal and regeneration: Wnt signaling and stem cell control.
Stem cells fuel tissue development, renewal, and regeneration, and these activities are controlled by the local stem cell microenvironment, the "niche." Wnt signals emanating from the niche can act as self-renewal factors for stem cells in multiple mammalian tissues. Wnt proteins are lipid-modified, which constrains them to act as short-range cellular signals. The locality of Wnt signaling dictates that stem cells exiting the Wnt signaling domain differentiate, spatially delimiting the niche in certain tissues. In some instances, stem cells may act as or generate their own niche, enabling the self-organization of patterned tissues. In this Review, we discuss the various ways by which Wnt operates in stem cell control and, in doing so, identify an integral program for tissue renewal and regeneration.


Catalytic efficiency of human alcohol dehydrogenases for retinol oxidation and retinal reduction.
Mammalian alcohol dehydrogenase (ADH) is thought to be involved in the reversible oxidation of vitamin A or retinol to retinal for retinoic acid synthesis. Retinoic acid is a potent transcriptional regulator and a morphogen. It was proposed that the competition of consumed ethanol with retinol oxidation by ADH might explain developmental disorders seen with fetal alcohol syndrome. We report herein the relative efficiency (V/Km) of eight human ADH isoenzymes for oxidation of all-trans-retinol and reduction of three retinal isomers (all-trans, 9-cis, and 13-cis-retinal). Class IV sigma sigma and class II pi pi isoenzymes are the most efficient forms, with V/Km values approximately 100 and 30 times greater, respectively, than class I beta 1 beta 1 or gamma 1 gamma 1, sigma sigma exhibits the highest V/Km (1-2 microns-1min-1), followed by pi pi, with V/Km of 0.5-0.6 microns-1min-1 for all-trans-retinol, all-trans-retinal, and 9-cis-retinal. pi pi also has the lowest Km (11-14 microns) for all-trans-retinol and three retinal isomers. alpha alpha shows an intermediate efficiency, with V/Km of 0.09-0.2 microns-1min-1 and a relatively low Km of 16-24 microns for all four substrates. alpha alpha has the highest efficiency of all tested isoenzymes for 13-cis-retinal. Class III chi chi is inactive with all the tested retinoids.(ABSTRACT TRUNCATED AT 250 WORDS)


Brainstem-vermis and brainstem-tentorium angles: 3D ultrasound study of the intra- and inter-observer agreement.
The brainstem-vermis angle (BVA) and the brainstem-tentorium angle (BTA) have been proposed to quantify vermian and tentorial alterations associated to fetal posterior fossa malformations. Our objective is to evaluate the intra- and inter-observer agreement for the measurement of these angles during the prenatal ultrasound scan. Fifteen 3 D sets from fetuses with posterior fossa pathology were processed by multiplanar navigation. Four experts in prenatal ultrasound measured the BVA and the BTA on a mid-sagittal view of the fetal brain, following the criteria described by Volpe. Observer 1 did also repeated measurements following both the criteria by Volpe and Ghi. The intraclass correlation coefficient (ICC) was used to test consistency and absolute agreement for intra- and inter-observer measurements. The concordance is poor when ICC <0.40 and excellent when ICC >0.75. Consistency ICC for measurements between the 4 observers was 0.74 (95% CI: 0.54-0.89) for the BVA and 0.55 (95% CI: 0.29-0.78) for the BTA. Absolute agreement ICC was 0.67 (BVA) and 0.45 (BTA). The intra-observer study showed a significantly greater angle with the criteria by Ghi (mean 52.1°, 95% CI: 49.5-54.8) than with the criteria by Volpe (mean 37.4°, 95% CI: 33.1-41.6). A more precise methodology for the measurement of these angles should be described.


[Research on spectral classification algorithm based on spatial feature].
With the wide use of imaging spectroscopy, applying data cubes to classification and identification of materials has been developed to be an important research content. The classification algorithms play a vital role in accuracy and precision of object identification. The most common classification algorithms mainly make use of the information gained from spectral dimension and classify the materials based on spectral match. The material reflectance spectra collected by imaging spectroscopy is determined not only by the sorts, but also by the geometry structure and roughness of material surface, and so on. Then classification and identification algorithms only using the reflection spectra have errors to some extent. This paper puts forward an algorithm based on the common classification algorithms that controls the classification process by using the spatial feature of image to promote the correctness of classification. This algorithm was applied to identify the true leaves from the fake ones. The result shows preferable spatial continuity. To a great extent, the algorithm overcomes "ma pixel" domino effect, and is proved valid.


Antigenic and functional analyses of glycoprotein of rabies virus using monoclonal antibodies.
Thirty-five monoclonal antibodies (MAbs) against glycoprotein (G protein) of the RC-HL strain of the rabies virus have been established. Using these MAbs, two antigenic sites (I and II) were delineated on the G protein of the RC-HL strain in a competitive binding assay. Of these, 34 MAbs recognized the epitopes on site II. Site II was further categorized into 10 subsites according to their patterns in a competitive binding assay. Each site II-specific MAb showed 5 to 23 nonreciprocal competitions. The reactivities of 35 MAbs to rabies and rabies-related viruses in an indirect immunofluorescent antibody test showed that six MAbs in group A binded to rabies and rabies-related viruses and eight MAbs in group E reacted only with rabies viruses, considering that the former represent the genus-specific of Lyssavirus and the latter are rabies virus-specific. From biological assays, 28 of the 35 MAbs showed neutralization activity, 31 showed hemagglutination inhibition (HI) activity, and 18 showed immunolysis (IL) activity. The MAbs recognizing neutralization epitopes fell into at least three groups: those exhibiting both HI and IL activity, those showing only HI activity, and those showing neither HI nor IL activity. All IL epitopes overlap with HA epitopes. Five of the nine MAbs which reacted with the antigen treated by sodium dodecyl sulfate in ELISA were not reduced, or reduced only slightly, in the titer. None of the MAbs reacted with 2-mercaptoethanol-treated antigen. Only one MAb that recognized site I reacted with the denatured G protein in a Western blotting assay, indicating that its epitope is linear. These results suggest that almost all of the epitopes on the G protein of the rabies virus are conformation-dependent and the G protein forms a complicated antigenic structure.


Mechanochemically Synthesised Coal-Based Magnetic Carbon Composites for Removing As(V) and Cd(II) from Aqueous Solutions.
The continued decrease in water quality requires new advances in the treatment of wastewater, including the preparation of novel, effective, environmentally friendly, and affordable sorbents of toxic pollutants. We introduce a simple non-conventional mechanochemical synthesis of magnetically responsive materials. Magnetic lignite and magnetic char were prepared by high-energy ball co-milling from either raw Slovak lignite or coal-based char together with a ferrofluid. The products were characterised by X-ray diffraction, electron microscopy, 57Fe Mössbauer spectroscopy, X-ray photoelectron spectroscopy (XPS), volumetric magnetic susceptibility, and low-temperature nitrogen adsorption, and both magnetic carbons were comparatively tested as potential sorbents of As(V) oxyanions and Cd(II) cations in aqueous solutions. The magnetic char was an excellent sorbent of As(V) oxyanions (Qm = 19.9 mg/g at pH 3.9), whereas the magnetic lignite was less effective. The different sorption properties towards arsenic anions may have been due to different oxidation states of iron on the surfaces of the two magnetic composites (determined by XPS), although the overall state of iron monitored by Mössbauer spectroscopy was similar for both samples. Both magnetic composites were effective sorbents for removing Cd(II) cations (Qm (magnetic lignite) = 70.4 mg/g at pH 6.5; Qm (magnetic char) = 58.8 mg/g at pH 6.8).


Skeletal Muscle Metastases from Carcinomas: A Review of the Literature.
* Bones are a common site for metastases; however, muscle metastases recently have been more commonly reported, not only as a result of the multidisciplinary approach in the treatment of these patients but also because of more sensitive imaging modalities such as positron emission tomography-computed tomography (PET-CT) that identify these lesions in early stages.* The most common carcinoma is lung carcinoma, with a hematogenous route of spread mainly to the axial region of the body (the psoas muscle, the gluteal muscles, and the paravertebral muscles). * Clinically, skeletal muscle metastases from carcinomas frequently present as painful palpable masses with or without swelling and are commonly found before diagnosis of the primary carcinoma.* Multiple imaging modalities, including radiographs, CT, magnetic resonance imaging (MRI), and PET-CT, have been used for diagnosis and staging, but tissue sampling is needed for a final diagnosis. The most important differential diagnosis of skeletal muscle metastases is with soft-tissue sarcomas.* Treatment is mainly based on chemotherapy and/or radiation; surgery is performed in cases of symptomatic lesions that fail to respond to nonoperative treatment.


Prospective risk analysis of the anti-infective medication administration process.
The objective of this study was to analyze the potential risks involved in the administration process of intravenous anti-infective medication at a medical clinic, using the Failure Mode and Effect Analysis. This exploratory study was conducted at the medical clinic of a hospital in the State of Goiás. For data collection we convened a team comprised of six professionals involved in medication treatment: a doctor, nurse, nursing technician, pharmacist, a nursing and a risk manager. A total of 24 meetings were held, for a total of 56 hours. The data were transcribed into an electronic database within Microsoft Excel®, and the Xfmea4 software was used. The results indicated 52 failure modes, 79 effects of failure, and 285 causes of failure. The causes were related to: the management of organizational processes, human resources, physical and material structure. A total of 298 actions for improvement were recommended for 215 causes of high and average priority, 81.9% of which were short-term priorities. The simulation of the impact of the proposed interventions revealed a 79.7% reduction of the high-priority failure modes. It was concluded that the study identified potential risks to patients and recommended proactive actions, of rapid application and low cost, evaluated positively in the reduction of risk of occurrence of avoidable incidents, increasing reliability and safety of the medication administration process. Studies like this demonstrate that, with the application of a method of risk analysis, nurses can effectively assist in preventing medication incidents.


Normal function of the thyroid gland in PUVA-treated psoriatics.
Ten psoriatics who were started on therapy with psoralen plus long-wave ultraviolet radiation (PUVA) were investigated for a possible influence of the treatment on the thyroid gland function. No statistically significant changes were found in the levels of serum thyroxine, triiodothyronine or thyrotropin obtained after 2 and 4 weeks' therapy and 3 months after cessation of therapy.


Classification of wheat varieties based on structural features of arabinoxylans as revealed by endoxylanase treatment of flour and grain.
Arabinoxylans (AX) are cell wall polysaccharides of complex structure involved in many aspects of wheat flour end uses. The study of the variations of AX structure can lead to the identification of genes involved in their biosynthesis, and thus in the control of the various aspects of grain quality related to their presence. A method is proposed to identify AX variations directly in whole grain by enzymatic degradation. An endoxylanase from Trichoderma viride was used to extract AX from a collection of 20 wheat cultivars (Triticum aestivum L.). Enzymatic degradation products were analyzed by HPAEC and multivariate analysis techniques (principal component analysis, canonical correlation analysis, and cluster analysis) were applied to analyze chromatographic data. The method evidenced variations in the proportion of mono- and disubstitution of the xylan backbone by arabinose side chains, allowing classification of the different varieties according to the structural features of AX. A similar classification was obtained starting from flour or whole grain, indicating that the method was specific of AX from endosperm tissues. In conclusion, the method combining endoxylanase treatment of wheat grain and the analysis of degradation products, e.g., enzymatic fingerprinting, can be applied to collections of wheat cultivars, and possibly other cereals in order to establish quantitative trait loci related to the biosynthesis of AX.


AtCAST3.0 update: a web-based tool for analysis of transcriptome data by searching similarities in gene expression profiles.
In transcriptome experiments, the experimental conditions (e.g. mutants and/or treatments) cause transcriptional changes. Identifying experimental conditions that induce similar or opposite transcriptional changes can be useful to identify experimental conditions that affect the same biological process. AtCAST (http://atpbsmd.yokohama-cu.ac.jp) is a web-based tool to analyze the relationship between experimental conditions among transcriptome data. Users can analyze 'user's transcriptome data' of a new mutant or a new chemical compound whose function remains unknown to generate novel biological hypotheses. This tool also allows for mining of related 'experimental conditions' from the public microarray data, which are pre-included in AtCAST. This tool extracts a set of genes (i.e. module) that show significant transcriptional changes and generates a network graph to present related transcriptome data. The updated AtCAST now contains data on >7,000 microarrays, including experiments on various stresses, mutants and chemical treatments. Gene ontology term enrichment (GOE) analysis is introduced to assist the characterization of transcriptome data. The new AtCAST supports input from multiple platforms, including the 'Arabisopsis gene 1.1 ST array', a new microarray chip from Affymetrix and RNA sequencing (RNA-seq) data obtained using next-generation sequencing (NGS). As a pilot study, we conducted microarray analysis of Arabidopsis under auxin treatment using the new Affymetrix chip, and then analyzed the data in AtCAST. We also analyzed RNA-seq data of the pifq mutant using AtCAST. These new features will facilitate analysis of associations between transcriptome data obtained using different platforms.


Ballistic diffusion induced by a thermal broadband noise.
We present a thermal broadband noise from the difference between two Ornstein-Uhlenbeck noises, which can induce a ballistic diffusion, i.e., long-time mean square displacement of a free particle driven by this noise reads <x(2)(t)> proportional to t(2). We apply this noise to a flashing ratchet and the mean velocity of the particle is calculated via Langevin simulation. The results show that a double peak of the mean velocity and flux reversal appears for the ratchet with large and small asymmetries, respectively; the inertia effect induces a large mean velocity and multireversal of flux. These rich and interesting phenomena are explained.


Pneumomediastinum and Subcutaneous Emphysema in an Adult Male From Nepal Infected With COVID-19.
Pneumomediastinum and subcutaneous emphysema have been reported in COVID-19 around the world except for Nepal. We report a case of a 44-year-old male infected with COVID-19 who developed pneumomediastinum and subcutaneous emphysema during his eighth day of intubation at the hospital. He was managed with remdesivir, antibiotics, mechanical ventilation, steroid, and heparin following which he recovered well. Barotrauma-related complications are common in COVID-19 and our case highlights the importance of conservative management for such complications and the rarity of such conditions in Nepal.


Access Control Mechanism for IoT Environments Based on Modelling Communication Procedures as Resources.
Internet growth has generated new types of services where the use of sensors and actuators is especially remarkable. These services compose what is known as the Internet of Things (IoT). One of the biggest current challenges is obtaining a safe and easy access control scheme for the data managed in these services. We propose integrating IoT devices in an access control system designed for Web-based services by modelling certain IoT communication elements as resources. This would allow us to obtain a unified access control scheme between heterogeneous devices (IoT devices, Internet-based services, etc.). To achieve this, we have analysed the most relevant communication protocols for these kinds of environments and then we have proposed a methodology which allows the modelling of communication actions as resources. Then, we can protect these resources using access control mechanisms. The validation of our proposal has been carried out by selecting a communication protocol based on message exchange, specifically Message Queuing Telemetry Transport (MQTT). As an access control scheme, we have selected User-Managed Access (UMA), an existing Open Authorization (OAuth) 2.0 profile originally developed for the protection of Internet services. We have performed tests focused on validating the proposed solution in terms of the correctness of the access control system. Finally, we have evaluated the energy consumption overhead when using our proposal.


[Inhibitory effect of potential metastasis in SGC-7901 cells induced by beta-ionone].
To determine the effect of beta-ionone on the potential metastasis of human gastric adenocarcinoma cell line SGC-7901 and the underlying mechanism. Using curve of cellular growth, Zymograms, and RT-PCR assays, we analyzed the growth rate, the activities of two types IV collagenase of Matrix met alloproteinase 9 (MMP-9) and MMP-2 and the expression of nm23-H1 gene, tissue inhibitor of met alloproteinase 1 (TIMP-1) and TIMP-2 in SGC-7901 cells which were treated with progressively increasing concentrations (25, 50, 100 and 200 micromol/L) of beta-ionone for 24 h and 48 h. The growth of SGC-7901 cells was inhibited by beta-ionone. Eight days after treatment with different concentrations of beta-ionone, as mentioned above, the inhibition rates were 25.93%, 28.21%, 74.36% and 90.11%, respectively compared to the negative control. The estimated IC50 value of beta-ionone for SGC-7901 cells was estimated to be 89 micromol/L; beta-ionone did not show any effect on the activities of MMP-9 and MMP-2 in SGC-7901 cells. However, the expression of nm23-H1, TIMP-1 and TIMP-2 mRNA transcripts gradually increased in response to beta-ionone in a dose-dependent manner. beta-ionone can inhibit the growth and proliferation of SGC-7901 cells. It may show some effects on the potential metastasis of SGC-7901 cells indicates by its upregulation of nm23-H1, TIMP-1 and TIMP-2 expression. However, beta-ionone may have no effect on the activities of type IV collagenase in SGC-7901 cells. The mechanism by which beta-ionone inhibits the potential metastasis of SGC-7901 cells needs to be studied further.


A Single-Batch Fermentation System to Simulate Human Colonic Microbiota for High-Throughput Evaluation of Prebiotics.
We devised a single-batch fermentation system to simulate human colonic microbiota from fecal samples, enabling the complex mixture of microorganisms to achieve densities of up to 1011 cells/mL in 24 h. 16S rRNA gene sequence analysis of bacteria grown in the system revealed that representatives of the major phyla, including Bacteroidetes, Firmicutes, and Actinobacteria, as well as overall species diversity, were consistent with those of the original feces. On the earlier stages of fermentation (up to 9 h), trace mixtures of acetate, lactate, and succinate were detectable; on the later stages (after 24 h), larger amounts of acetate accumulated along with some of propionate and butyrate. These patterns were similar to those observed in the original feces. Thus, this system could serve as a simple model to simulate the diversity as well as the metabolism of human colonic microbiota. Supplementation of the system with several prebiotic oligosaccharides (including fructo-, galacto-, isomalto-, and xylo-oligosaccharides; lactulose; and lactosucrose) resulted in an increased population in genus Bifidobacterium, concomitant with significant increases in acetate production. The results suggested that this fermentation system may be useful for in vitro, pre-clinical evaluation of the effects of prebiotics prior to testing in humans.


Stem Cell-Containing Hyaluronic Acid-Based Spongy Hydrogels for Integrated Diabetic Wound Healing.
The detailed pathophysiology of diabetic foot ulcers is yet to be established and improved treatments are still required. We propose a strategy that directs inflammation, neovascularization, and neoinnervation of diabetic wounds. Aiming to potentiate a relevant secretome for nerve regeneration, stem cells were precultured in hyaluronic acid-based spongy hydrogels under neurogenic/standard media before transplantation into diabetic mice full-thickness wounds. Acellular spongy hydrogels and empty wounds were used as controls. Re-epithelialization was attained 4 weeks after transplantation independently of the test groups, whereas a thicker and more differentiated epidermis was observed for the cellular spongy hydrogels. A switch from the inflammatory to the proliferative phase of wound healing was revealed for all the experimental groups 2 weeks after injury, but a significantly higher M2(CD163+)/M1(CD86+) subtype ratio was observed in the neurogenic preconditioned group that also failed to promote neoinnervation. A higher number of intraepidermal nerve fibers were observed for the unconditioned group probably due to a more controlled transition from the inflammatory to the proliferative phase. Overall, stem cell-containing spongy hydrogels represent a promising approach to enhance diabetic wound healing by positively impacting re-epithelialization and by modulating the inflammatory response to promote a successful neoinnervation.


[Hypoparathyroidism and pseudohypoparathyroidism. New aspects of the pathogenesis, diagnosis and therapy].
Recent elucidations of normal and disturbed parathyroid secretion and action have provided a basis for the understanding of general principles of endocrinology. Advanced laboratory methods and simplified study protocols have improved the diagnosis of hypoparathyroidism and pseudohypoparathyroidism, the most important feature of which is chronic hypocalcemia. The knowledge of these disorders is of great importance to the pediatrician since they occur in childhood, and the consequences of prolonged misdiagnosis and inadequate treatment may be serious.


[Results of resection treatment of locally limited bronchial carcinoma (Stages I and II)].
Of 238 patients operated upon for bronchogenic carcinoma between 1977 and 1985 the tumor was locally limited in 108, of whom, according to the new international staging system, 66 patients were in stage I (T1N0 + T2N0) and 42 in stage II (T1N1 + T2N1). 89 were male and 19 (18%) female. The mean age was 61.6 years in stage I und 63 years in stage II patients. 26 patients (24%) were aged over 70. All patients underwent potentially curative excision of the tumor. This was accomplished by partial lung resection in 97 patients, of whom 84 underwent lobectomy with 2 postoperative deaths (2.4%). Operative mortality amounted to 5.5% in the whole group (6/108), with 3% (2/66) in stage I and 9.5% (4/42) in stage II patients. The absolute survival rate at 5 years was 50% for all 108 patients, 59% for the 66 patients in stage I and 39% for the 42 patients in stage II. It was 70% for 15 patients with bronchioloalveolar carcinoma, 54% for 20 patients with adenomatous cancer and 49% for 56 patients with squamous carcinoma. At present 62 of the 108 patients are still alive (57.4%), i.e. 45 out of 66 in stage I (68%) and 17 out of 42 in stage II (40.5%). This retrospective study therefore confirms former reports that long term results are encouraging in the locally limited stages of pulmonary cancer. In addition, operative mortality is low because almost all these tumors can be removed by partial lung resection. In stage I lobectomy is the method of choice.