Structural and biochemical characterization and evolutionary relationships of the fatty acid-binding protein 10 (Fabp10) of hake (Merluccius hubbsi).
A fatty acid-binding protein (FABP) from the liver of Argentine hake (Merluccius hubbsi) was isolated and characterized and its expression analyzed. The determination of its partial primary structures (72%) showed that it presents highest identity with Fabp10, commonly termed liver basic-type FABP. The evolutionary tree showed greater relationship between the Fabp10 of hake (Me Fabp10) and the Fabp10 and the Fabp10a of teleost fish. Me Fabp10 had low affinity for palmitic, oleic and palmitoleic acid and high affinity for bilirubin, lysophosphatidylcholine and lysophosphatidylethanolamine, all of them important in the metabolic functions of the liver. Me Fabp10 was able to bind only one cis-parinaric acid molecule and was found to be expressed only in the liver.


New orbitozygomatic approach by craniotomy.
The orbitozygomatic extension technique described by Sekhar and Wright requires a temporal basal craniectomy that must be done in order to make osteotomy dissections. In the present work, a technique that includes the base and squamous temporal bone and a craniotomy instead of a craniectomy is shown. The temporal and masseter muscles are dissected and separated from the temporal and zygomatic bones to facilitate passing them through the zygomatic arch in a caudal direction, which allows a frontotemporal basal craniotomy. Intracranially, a trepan that communicates to the glenoid cavity is done, which permits a temporal basal cut using the pneumatic drill saw. This is done in order to join with the orbital wall osteotomies, which were done in this approach with the craniotomy.


Doppler predictions of pulmonary artery pressure, flow, and resistance in adults.
We examined the accuracy of noninvasive predictions of pulmonary artery pressure (P), flow (Q), and resistance (R) by means of main pulmonary artery blood velocities and diameters measured with Doppler echocardiography (DE). The ratio of noninvasive acceleration time to ejection time (An) was correlated to invasively determined mean pulmonary artery pressure (Pl) and resistance (Rl). Noninvasive flows were correlated to thermodilution flows (Ql). Simultaneous invasive and noninvasive measurements were made in nine adult patients (ages = 22 to 73 years). The results were: Pl = 87 - 152An, r = 0.90, SEE = 7 mm Hg, p less than 0.05; Rl = 899 - 1722An, r = 0.79, SEE = 121 dynes X sec X cm-5, p less than 0.05; and Ql = -0.3 + 1.21Qn, r = 0.95, SEE = 0.81 L X min-1, p less than 0.05. We then used these equations prospectively to predict Pl, Rl, and Ql in 21 of 25 (83% technically adequate) consecutive patients. Pl, Rl, and Ql ranged from 10 to 35 mm Hg, 39 to 456 dynes X sec X cm-5, and 3.51 to 8.39 L X min-1, respectively. Results were: Pl = 0.80P + 3, r = 0.72, SEE = 6 mm Hg, p less than 0.05; Rl = 0.75R - 12, r = 0.64, SEE = 77 dynes X sec X cm-5, p less than 0.005; and Ql = 0.87Q + 0.38, r = 0.83, SEE = 0.86 L X min-1, p less than 0.05. These results suggest that DE predictions of pulmonary artery pressure, flow, and resistance correlate significantly with values subsequently obtained at catheterization.


Dissolution of synthetic uranium dibutyl phosphate deposits in oxidizing and reducing chemical formulations.
Permanganate and nitrilotriacetic acid (NTA) based dilute chemical formulations were evaluated for the dissolution of uranium dibutyl phosphate (U-DBP), a compound that deposits over the surfaces of nuclear reprocessing plants and waste storage tanks. A combination of an acidic, oxidizing treatment (nitric acid with permanganate) followed by reducing treatment (NTA based formulation) efficiently dissolved the U-DBP deposits. The dissolution isotherm of U-DBP in its as precipitated form followed a logarithmic fit. The same chemical treatment was also effective in dissolving U-DBP coated on the surface of 304-stainless steel, while resulting in minimal corrosion of the stainless steel substrate material. Investigation of uranium recovery from the resulting decontamination solutions by ion exchange with a bed of mixed anion and cation resins showed quantitative removal of uranium.


Dysregulated lipid metabolism blunts the sensitivity of cancer cells to EZH2 inhibitor.
Sensitivity has been a key issue for Enhancer of zeste homolog 2 (EZH2) inhibitors in cancer therapy. The EZH2 inhibitor EPZ-6438 was first approved by the US Food and Drug Administration (FDA) in 2020. However, its inadequate anti-cancer activity in solid tumors limits its clinical application. In this study, we utilized the multiple cancer cell lines, which are less sensitive to the EZH2 inhibitor GSK126, combining animal model and clinical data to investigate the underlying mechanism. IncuCyte S3 was used to explore the difference in the responsiveness of hematological tumor cells and solid tumor cells to GSK126. Transcriptome and metabolome of B16F10 cells after GSK126 treatment were analyzed and the distinct changes in the metabolic profile were revealed. Real-time quantitative PCR and western blot experiments were used to further verify the multi-omics data. ChIP-qPCR was performed to detected H3K27me3 enrichment of target genes. Finally, the anti-tumor effects of combining GSK126 and lipid metabolism drugs were observed with IncuCyte S3 platform, CCK-8 and animal model respectively. We found that although the proliferative phenotype did not show strong difference upon treatment with GSK126, the transcriptome and metabolome changed profoundly. GSK126 treatment led to broad shifts in glucose, amino acid, and lipid metabolism. Lipid synthesis was strengthened manifested by the increasing abundance of unsaturated fatty acids. SCD1 and ELOVL2 were regulated by H3K27me3 at gene regulatory region, and upregulated by EZH2 knockdown and inhibitors. SCD1 knockdown increased cellular sensitivity to GSK126. Based on the findings above, the application of the combination with SCD1 inhibitor significantly attenuated the proliferation of cancer and increased the sensitivity to GSK126 by suppressing desaturation of fatty acids. Dysregulated lipid metabolism can blunt the sensitivity of cancer cells to GSK126. These characteristics shed light on the novel combination therapy strategies to combat tumor resistance. National Natural Science Foundation of China (No. 81672091, No.91749107 and No. 81972966).


NA1/NA2 antisera inhibit FcgammaRI- but not FcgammaRII- mediated phagocytosis.
Alloantibodies against the granulocyte-specific NA antigens play an important role in alloimmune neonatal neutropenia. As the NA system is located on the FcgammaRIIIb, the influence of NA-specific antibodies on granulocyte function is of special interest. We tested alloantisera specific for NA1 and NA2 for their ability to influence FcgammaR-mediated phagocytosis of polymorphonuclear neutrophils by use of different FcgammaR-specific targets. Red blood cells coated with human IgG anti-D served as specific targets for FcgammaRI-mediated phagocytosis while mouse IgG1 anti-glycophorin A was used to coat red blood cells (RBCs) to obtain FcgammaRII specific targets. To test for a hypothetical induction of phagocytosis by FcgammaRIIIb we used D-- RBCs coated with human monoclonal anti-D as target cells for unprimed neutrophils. Granulocyte phagocytosis was directly induced by FcgammaRI and FcgammaRII but not by FcgammaRIIIb. NA1 alloantisera significantly inhibited FcgammaRI-mediated phagocytosis of IFN-gamma-stimulated neutrophils if the corresponding antigen was expressed. Conversely, NA2 alloantisera inhibited FcgammaRI-mediated phagocytosis in NA2-positive individuals. There was no effect of NA1- and NA2-specific alloantibodies on FcgammaRII-mediated phagocytosis. NA-specific alloantisera inhibit the FcgammaRI-induced phagocytosis in primed neutrophils, but they do not significantly inhibit their FcgammaRIIa-specific phagocytosis of mIgG1-coated RBCs.


Psychosocial stressors and well-being in health care workers. The impact of an intervention program.
There have been few prospective studies of the impact of workplace interventions on employee and organizational well-being within health care settings. This study was conducted at a large regional hospital in Sweden in 1994 with a follow-up in 1995. Effects of a structured organizational and staff intervention program on perceived psychosocial work quality, supporting resources and self-reported health and well-being were evaluated. Based on department-specific results from the baseline assessment in 1994, each department formulated their own improvement goals. They also made their own decisions on relevant improvement activities. Since there was no formal reference group in this study, departments with high and low rating levels, respectively, with regard to intervention activities were compared. Despite an overall worsening in most of the measures most likely due to a notice of 20% staff reduction prior to the follow-up assessment, the intervention appeared to have attenuated negative changes in the high as compared with the low activity group. Manager-rated impact of the program as well as positive staff attitudes and staff involvement in the enhancement process were identified as important determinants for more favourable changes. The study points out the relevance of structured workplace interventions for organizational and employee well-being especially in times of cut-backs and organizational turmoil. Department-specific factors will determine the impact of such programs. The study indicates that the psychosocial impact of personnel cut-backs in health care may be attenuated through management initiatives.


[Findings in brainstem auditory evoked potentials in patients under 2 years of age with a history of intraventricular haemorrhage].
There are few studies that describe the results of auditory pathway assessment in patients with a history of intraventricular haemorrhage (IVH) during the early years of life. Hypoacusis can occur from the earliest stages of IVH. Brainstem auditory evoked potentials (BAEPs) are a useful tool for diagnosing auditory pathway disorders in early childhood. The aim of the present study was to describe the BAEPs findings in patients under 2 years of age with a history of IVH. We conducted a retrospective observational study in patients under 2 years of age with a history of IVH referred to our hospital for BAEPs over a period of three years. Patients with genetic syndromes associated with hypoacusis were excluded. BAEPs were used to evaluate the presence or absence of any bioelectrical response and latencies of waves I, III and V, as well as of the intervals I-III, III-V and I-V, and also their morphology, amplitude, synchrony and reproducibility. A descriptive analysis was carried out with the calculation of frequencies and percentages. A total of 122 patients were included. Fifty-one per cent of them had a history of Grade I IVH; 42%, Grade II; and 7%, Grades III or IV. A bioelectrical response was obtained in 243 auditory pathways (99.6%). The morphology was found to be altered in 6.2% of the auditory pathways, while amplitudes were decreased in 2.5% of those tested. Latencies for waves I and III were found to be prolonged in 2% and for wave V in 3.6% of patients. The hearing threshold was normal in 64.8%, and 35.2% of cases presented hypoacusis. The prevalence of hypoacusis was high in the sample analysed. Systematic follow-up using BAEPs is recommended in order to detect and treat problems in the auditory pathway in patients with IVH in a timely manner.


A study on the microheterogeneity of alpha-fetoproteins produced by yolk sac and germ cell tumors.
It is generally believed that the lower the grade of differentiation of glycoprotein-producing cells, the more often modification by bisecting N-acetylglucosamine (GlcNAc) or fucose (Fuc) at the sugar chain of the glycoprotein or increase in branching of side chains occurs. We examined the characteristics of the alpha-fetoprotein (AFP) sugar chain stored in amniotic and exocoelomic fluid during 5-9 weeks of gestation and analyzed serum-derived AFP of patients with germ cell tumors. Total AFP concentrations in embryonic fluid at 5-9 weeks of gestation (n = 11) and serum of patients with germ cell tumors (n = 7) were measured using a radioimmunoassay (RIA) method. The percentages of AFPs reactive with Lens culinaris agglutinin (LCA), concanavalin A (Con A), erythroagglutinating phytohemagglutinin-E4 (E-PHA) and Ricinus communis agglutinin-120 (RCA 120) were obtained by lectin-affinity electrophoresis coupled with antibody-affinity blotting. It was revealed that at 5-9 weeks of gestation, AFP variants that had been modified by the Fuc residue, which bound to the GlcNAc residue at the reducing end of the sugar chain, and bisecting GlcNAc residues gradually decreased as pregnancy advanced; however, the presence of N-acetylneuraminic acid (Neu5Ac) at the nonreducing ends changed little. It appears very likely that the changes in the relative amounts of AFP variants in the embryonic fluid during early pregnancy were due to differentiation of the yolk sac. The grade of differentiation of yolk sac tumors was very similar to that of the normal yolk sac at around 6 weeks of gestation.


Chemokines IL-8, GROalpha, MCP-1, IP-10, and Mig are sequentially and differentially expressed during phase-specific infiltration of leukocyte subsets in human wound healing.
Healing of cutaneous wounds requires a complex integrated network of repair mechanisms, including the action of newly recruited leukocytes. Using a skin repair model in adult humans, we investigated the role chemokines play in sequential infiltration of leukocyte subsets during wound healing. At day 1 after injury, the C-X-C chemokines IL-8 and growth-related oncogene alpha are maximally expressed in the superficial wound bed and are spatially and temporally associated with neutrophil infiltration. IL-8 and growth-related oncogene alpha profiles also correlate with keratinocyte migration and subsequently subside after wound closure at day 4. Macrophage infiltration reaches the highest levels at day 2 and is paralleled by monocyte chemoattractant protein-1 mRNA expression in both the basal layer of the proliferative epidermis at the wound margins and mononuclear cells in the wound area. Other monocyte-attracting chemokines such as monocyte chemoattractant protein-3, macrophage inflammatory protein-1alpha and -1beta, RANTES, and 1309 are undetectable. At day 4, perivascular focal lymphocyte accumulation correlates with strong focal expression of the C-X-C chemokines Mig and IP-10. Our results suggest that a dynamic set of chemokines contributes to the spatially and temporally different infiltration of leukocyte subsets and thus integrates the inflammatory and reparative processes during wound repair.


Advancing Best Practices for Prescription Drug Labeling.
Problematic prescription drug labeling has been cited as a root cause of patient misunderstanding, medication errors, and nonadherence. Although numerous studies have recently been conducted to identify and test labeling best practices, the last systematic review on this topic was conducted a decade ago. The objective of this review was, therefore, to examine, summarize, and update best practices for conveying written prescription medication information and instructions to patients. English-language articles published from June 2005 to June 2015 were identified in MEDLINE and CINAHL by searching the following text words: 'medication OR prescription OR drug' AND 'label OR leaflet OR brochure OR pamphlet OR medication guide OR medication insert OR drug insert OR medication information OR drug information OR instructions' AND 'patient OR consumer.' Reference mining and secondary searches were also performed. A total of 31 articles providing evidence on how to improve written, prescription drug labeling for patient use were selected. Two reviewers independently screened articles, rated their quality, and abstracted data. Identified best practices included the use of plain language, improved formatting and organization, and more explicit instructions to improve patient comprehension. The use of icons had conflicting findings, and few studies tested whether practices improved knowledge or behaviors with patients' actual prescribed regimens. Future studies are needed to determine how specific modifications and improvements in drug labeling can enhance patient knowledge and behavior in actual use. Synthesizing best practices across all patient materials will create a more useful, coordinated system of prescription information.


[State of the tone and reactivity of the vascular wall in patients with chronic alcoholism during therapy].
With the aid of the rheoencephalographical and rheovazographical methods the authors revealed some objective criteria of a change of reactivity of brain vessels and peripheral vessels--the hypertonus of the vascular wall combined with a decreased pulse blood filling, a decrease of elasticity of the vascular wall. The pathogenetical validity of the inclusion of psychotropic drugs and insulin-sub-shock therapy into the scheme of antialcoholic treatment is proved.


Use of physical and neurologic observations in assessment of gestational age in low birth weight infants.
The relative validities of three clinical assessment methods for estimating gestational age in newborn low birth weight infants were evaluated with reference to estimates based on the date of the mother's last menstrual period. For 1246 infants in eight diverse institutions, estimates based on physical criteria correlated more strongly with dates estimates, yielded estimates more similar on average to dates estimates, and yielded higher proportions of correct classifications of prematurity and small for gestational age than did estimates based on neurologic criteria or neurologic and physical criteria combined. These results support the use of physical criteria rather than neurologic or combined criteria for the clinical assessment of gestational age in low birth weight infants. In a subsample of 511 black and white infants, there were no ethnic differences in mean error of estimate for any of the three methods.


Simultaneous extraction and catalytic adsorptive stripping voltammetric measurement of Cr(VI) in solid samples.
A fast, simple, sensitive and economical method for Cr(VI) extraction and determination in solid samples was developed and evaluated. The presented protocol for Cr(VI) determination in solid samples allows for simultaneous extraction and determination of Cr(VI) in one step. The procedure is based on a quantitative extraction method in which the complexing properties of diethylenetriaminepentaacetic acid (DTPA) were exploited to extract total Cr(VI) (soluble and insoluble forms) from the solid sample. A catalytic adsorptive stripping voltammetric technique is employed for direct determination of Cr(VI) in the extract. The effects of analytical parameters such as temperature, pH, composition and concentration of the supporting electrolyte (which simultaneously plays the role of extractant), extraction and accumulation time were investigated. The accuracy of the proposed procedure was tested by analyzing certified reference materials CRM 013 Paint Chips and CRM 019 Ash. The results obtained were compared with the results obtained using two other reference extraction procedures. The effects of potentially interfering ions which generally accompany Cr(VI) in natural samples on the Cr(VI) determination, with special notice to Cr(III) interference, are reported.


On the non-uniqueness problem in integrated information theory.
Integrated Information Theory (IIT) 3.0 is among the leading theories of consciousness in contemporary neuroscience. The core of the theory relies on the calculation of a scalar mathematical measure of consciousness, Φ, which is inspired by the phenomenological axioms of the theory. Here, we show that despite its widespread application, Φ is not a well-defined mathematical concept in the sense that the value it specifies is non-unique. To demonstrate this, we introduce an algorithm that calculates all possible Φ values for a given system in strict accordance with the mathematical definition from the theory. We show that, to date, all published Φ values under consideration are selected arbitrarily from a multitude of equally valid alternatives. Crucially, both [Formula: see text] and [Formula: see text] are often predicted simultaneously, rendering any interpretation of these systems as conscious or not, non-decidable in the current formulation of IIT.


Incidence and risk factors of bacterial infections in children following autologous hematopoietic stem cell transplantation: Single-center experience from Jordan.
Bacterial infection is a serious sequela following AHSCT; however, limited data are available regarding pediatric recipients, especially in developing countries. We retrospectively analyzed the incidence and risk factors of bacterial infections during the first 100 days after AHSCT in children at KHCC in Amman, Jordan between January, 2005 and September, 2013. A total of 65 patients were identified, with median age of four yr (1-17). Forty-seven patients (72.3%) had solid tumors and 18 (27.7%) had lymphoma. Bacterial infections were documented in 33 patients (50%), with a total of 63 episodes. Gram-negative infection (57.1%) was more prevalent than Gram-positive infection (38%). The risk of bacterial infections was higher among patients less than five yr of age (p = 0.028) and those who developed hypogammaglobulinemia requiring IVIG replacement (p = 0.001). Patients with solid tumors developed more bacterial infections compared to patients with lymphoma (p = 0.0057). No deaths were attributed to bacterial infection. Bacterial infection rate is high among recipients of AHSCT in Jordan with Gram-negative bacteria being the most common.


Gene Expression Profiling as a New Real-Time Assay in Human Biomonitoring of Waste-to-Energy Plant Workers.
Exposure to heavy metals represents one of the most important risk factors for the health of incinerator workers. Indeed, heavy metals can determine increased generation of reactive oxygen species (ROS). In this work, we introduced the use of transcription profiling of detoxifying genes, involved in redox balance and genome integrity, as a highly sensitive assay of heavy metal exposure and subsequent oxidative stress. For this purpose, blood mRNA levels of OGG1, ST13, NQO1 and MT1A genes, as well as urinary concentrations of nine heavy metals and the oxidized base 8-OHdG of 49 subjects (26 controls and 23 employees in the waste-to-energy plant of San Zeno, Arezzo, Italy) were determined. No significant difference between the two populations was observed, thus highlighting, as far as the biomarkers analysed are concerned, the absence of occupational exposure to heavy metals and systemic oxidative stress induction in the workers of the waste-to-energy plant of San Zeno. Correlation analyses underline a close association between heavy metals exposure and changes in expression levels of a number of genes, even at low exposure doses, thus remarking the greater capacity of detection of transcription profiling compared to other biomarkers and the importance of its introduction in future human biomonitoring programs.


Evaluation of the mediastinum by gallium-67 scintigraphy in lung cancer.
Delineation of the metastatic spread of lung cancer has been attempted by a variety of means. Controversy as to the indications for organ surveys, mediastinoscopy, scintillation scanning, and biopsy techniques still exists. Since definition of the micrometastatic state is yet unachieved, the staging of disease for therapy continues to be predicted on documented spread beyond the site of the origin. The records of 75 patients in whom the presence or absence of mediastinal metastases was known were retrospectively reviewed to establish the sensitivity, specificity, predictive values, and accuracy of 67Ga scintigrams. Comparisons were made with chest roentgenograms, mediastinal tomograms, and endoscopic findings. Five patients had 67Ga-negative studies. In the 70 patients having 67Ga-positive lung lesions, mediastinal 67Ga uptake had a sensitivity of 88%, a specificity of 86%, predictive values of 93% for a positive test and 76% for a negative test, and a test accuracy of 87%. These studies, plus those of others, permit selectivity of choosing candidates for mediastinoscopy. If the primary is 67Ga positive, a negative mediastinal scan obviates mediastinoscopy. If the mediastinum is 67Ga positive, mediastinal exploration is indicated. The level of involvement dictates whether resection is undertaken in suitable surgical candidates. This approach, employed since 1976, has lowered the costs of staging, and 67Ga has become our scintigram of choice.


Molecular mechanism of membrane targeting by the GRP1 PH domain.
The general receptor for phosphoinositides isoform 1 (GRP1) is recruited to the plasma membrane in response to activation of phosphoinositide 3-kinases and accumulation of phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P(3)]. GRP1's pleckstrin homology (PH) domain recognizes PtdIns(3,4,5)P(3) with high specificity and affinity, however, the precise mechanism of its association with membranes remains unclear. Here, we detail the molecular basis of membrane anchoring by the GRP1 PH domain. Our data reveal a multivalent membrane docking involving PtdIns(3,4,5)P(3) binding, regulated by pH and facilitated by electrostatic interactions with other anionic lipids. The specific recognition of PtdIns(3,4,5)P(3) triggers insertion of the GRP1 PH domain into membranes. An acidic environment enhances PtdIns(3,4,5)P(3) binding and increases membrane penetration as demonstrated by NMR and monolayer surface tension and surface plasmon resonance experiments. The GRP1 PH domain displays a 28 nM affinity for POPC/1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoethanolamine/PtdIns(3,4,5)P(3) vesicles at pH 6.0, but binds 22-fold weaker at pH 8.0. The pH sensitivity is attributed in part to the His355 residue, protonation of which is required for the robust interaction with PtdIns(3,4,5)P(3) and significant membrane penetration, as illustrated by mutagenesis data. The binding affinity of the GRP1 PH domain for PtdIns(3,4,5)P(3)-containing vesicles is further amplified (by approximately 6-fold) by nonspecific electrostatic interactions with phosphatidylserine/phosphatidylinositol. Together, our results provide new insight into the multivalent mechanism of the membrane targeting and regulation of the GRP1 PH domain.


A health promotion program: Staying Healthy After Fifty.
In this article, a description of how a comprehensive health promotion program for older adults was developed, tested with a quasi-experimental study design, and then revised to become a nationwide AARP and Red Cross program is presented. Teaching and learning methods used in the course are described with supporting education and behavioral theory. The course content for instructors, facilitators, and course participants is outlined. The key elements in the preparation of instructors and facilitators are identified. Results of the implementation of the program are given.


The inactivation of prostaglandin E2 is decreased by dipyridamole and sulfinpyrazone in isolated rat lungs.
The inactivation of prostaglandin E2 (PGE2) was decreased in the pulmonary circulation of isolated rat lungs, when either dipyridamole or sulfinpyrazone was infused into the pulmonary artery at the concentration of 20 microM. After pulmonary injection of 7.1 nmoles of 14C-PGE2 the amount of 15-oxo-metabolites of PGE2 in the effluent was 3.91 +/- 0.19 nmoles from control lungs and 2.05 +/- 0.19 nmoles (2P less than 0.001) in that from 20 microM dipyridamole treated lungs. The corresponding values for control and 20 microM sulfinpyrazone lungs were 4.11 +/- 0.25 and 3.03 +/- 0.14 nmoles (2P less than 0.01), respectively. The amounts of unmetabolized PGE2 were correspondingly increased in the effluents from dipyridamole and sulfinpyrazone (20 microM) lungs. Neither dipyridamole nor sulfinpyrazone had at concentration of 2 microM any significant effect on the amount of 15-oxo-metabolites in the effluent, although the amount of unmetabolized PGE2 was slightly increased in 2 microM sulfinpyrazone experiments.


Fetal Neuroimaging Updates.
MR imaging is used in conjunction with ultrasound screening for fetal brain abnormalities because it offers better contrast, higher resolution, and has multiplanar capabilities that increase the accuracy and confidence of diagnosis. Fetal motion still severely limits the MR imaging sequences that can be acquired. We outline the current acquisition strategies for fetal brain MR imaging and discuss the near term advances that will improve its reliability. Prospective and retrospective motion correction aim to make the complement of MR neuroimaging modalities available for fetal diagnosis, improve the performance of existing modalities, and open new horizons to understanding in utero brain development.


Loss of muscarinic M4 receptors in spinal cord of arthritic rats: implications for a role of M4 receptors in pain response.
Changes in the levels of muscarinic M4 receptors in spinal cord of acute and chronic arthritic rats (animal models of pain) were studied by receptor autoradiography using muscarinic M4 receptor subtype selective ligand. Arthritis was induced in female Lewis rats by single intradermal injection of heat-killed Mycobacterium butyricum and sacrificed 12 days (acute group) and 30 days (chronic and control groups) after induction of arthritis. Our results demonstrate significant reduction in the level of M4 receptors in the spinal cord (Rexed laminae I-X) of acute and chronic arthritic rats compared to controls. These findings suggest that the muscarinic M4 receptor subtype may be involved in cholinergic mechanisms of analgesia.


Calcitonin gene-related peptide immunoreactive sensory and motor nerves of the rat, cat, and monkey esophagus.
In the mammalian esophagus calcitonin gene-related peptide (CGRP)-immunoreactive nerves form abundant subepithelial plexuses and penetrate the mucosa. The levels of extractable CGRP in separated epithelial layers are 15.8 +/- 2.4 pmol/g wet wt of tissue (n = 8, mean +/- SEM). Treatment of neonatal rats with capsaicin and ablation of the central portion of the feline nodose ganglion led to a marked reduction in the numbers of CGRP-immunoreactive nerve fibers. The loss of CGRP nerves demonstrated by immunocytochemistry was accompanied by a parallel reduction in the tissue content of CGRP, as measured by radioimmunoassay (1.5 +/- 0.5 pmol/g in capsaicin-treated animals compared with 9.4 +/- 1.9 pmol/g in vehicle-treated controls; p less than 0.0025). These findings indicate the sensory nature of the CGRP-immunoreactive nerves. Substance P-immunoreactive nerve fibers innervated in particular the blood vessels of the lamina propria; very few penetrated the esophageal epithelium and these were only partially depleted after removal of the central portion of the nodose ganglion. The esophageal muscle contained nerves immunoreactive for substance P and, in particular, for CGRP which was also found in the motor end plates of the striated muscle. No changes in the CGRP-containing motor end plates were observed either after treatment of neonatal rats with capsaicin or ablation of cell bodies from the central portion of the nodose ganglion. These nerve fibers may originate from rostral areas of the nucleus ambiguus, where CGRP-immunoreactive motor neurons have previously been described. Thus, our findings reveal dual components, motor and sensory, of the CGRP-containing innervation of the esophagus.


Il10 and poly-dl-lactide-ɛ-caprolactone conduits in critical size nerve defect bridging-An experimental study.
Aim of this study is to evaluate if regeneration in repair of nerve defects can be improved by combination of a poly-dl-lactide-ɛ-caprolactone conduit (PLC) with long-term release of anti-inflammatory Interleukin 10 (IL10), which is known to reduce intraneural scarring in nerve regeneration through its anti-inflammatoric properties. Experiments were performed at 30 female Lewis rats. Conduits filled with fibrin (PLC-group n = 10) and fibrin loaded with IL10 (IL10-group n = 10) were compared to autologs nerve grafts (NG-group n = 10) in a 15 mm sciatic nerve gap lesion. Sciatic function index (SFI) and electrophysiological analyses were performed 16 weeks after surgery prior to histological evaluation. In histological analyses total nerve count, total nerve area, myelination index, and N-ratio were measured. Additionally, gastrocnemius muscle was weighed. SFI (NG-group:-50.68 ± 7.03%; PLC-group:-56.48 ± 2.30%; IL10-group:-56.54 ± 8.22%) and nerve conduction velocity (NG-group: 92.52 ± 4.64 m/s; PLC-group: 92.77 ± 5.07 m/s; IL10-group: 93.78 ±3.63 m/s) showed no significant differences after 16 weeks (P > 0.05). Significant higher axon count (17.592 ± 483) were observed in the NG-group compared to PLC- (6.722 ± 553) and IL10-group (6.842 ± 681) (P < 0.001). NG-group had significant highest nerve cross sections (604.214 ± ±15.217 µm2 ) as compared to PLC- (245.669 ± ±28.034 µm2 ) and IL10-group (244.698 ± 26.772 µm2 ) (P < 0.001). Comparison of myelination index showed significant higher values for NG-group (0.46 ± 0.02) than PLC- (0.64 ± 0.01) and IL10-group (0.62 ± 0.01) (P < 0.001). N-ratios in PLC-group (0.21 ± 0.01) and IL10-group (0.24 ± 0.01) were lower than in NG-group (0.51 ± 0.03) (P < 0.001). Between PLC- and IL10-group no differences were observed (P > 0.05). Gastrocnemius muscle was heavier in NG-group (0.86 ± 0.21g) as compared to PLC- (0.26 ± 0.05g) and IL-10 group (0.29 ± 0.06 g) (P < 0.05). Bridging critical nerve defects through fibrin-filled PLC conduits is possible. Although, autologs nerve graft showed superior histological results. Long-term release of IL10 in the conduit did not improve regeneration of critical nerve defects. © 2015 Wiley Periodicals, Inc. Microsurgery 36:410-416, 2016.


Hydrolase activities in the rat aorta. II. Effects of hypertension alone and in combination with diabetes mellitus.
Hypertension is an important risk factor for atherosclerosis and often occurs in association with diabetes mellitus. Specific activities of hydrolases in homogenates of aortas from rats with renal-clip hypertension, normotension following a period of hypertension, and hypertension combined with streptozotocin-induced diabetes mellitus were measured. Enzymes included: neutral alpha-glucosidase, and lysosomal N-acetyl-beta-glucosaminidase, beta-galactosidase, cathepsin C, acid alpha-glucosidase, and acid cholesteryl esterase. After 6 or 12 weeks of hypertension, specific activities of all enzymes measured were significantly increased, levels ranging from 24% above normal for cathepsin C to 351% above normal for N-acetyl-beta-glucosaminidase. Six weeks of normotension following 6 weeks of hypertension resulted in restoration to normal of four of the six enzyme activities; the remaining two enzymes were significantly below normal levels. Combined hypertension and diabetes mellitus showed smooth muscle cell levels of four of the five hydrolases measured to be significantly lower than those present with hypertension alone. In every instance, histochemical studies of aortas showed acid phosphatase and N-acetyl-beta-glucosaminidase activities which corresponded to the biochemical findings. These findings indicate profound and discrete effects of two clinical risk factors on vascular smooth muscle cell lysosomes.


Quantitative analysis of glycans, related genes, and proteins in two human bone marrow stromal cell lines using an integrated strategy.
Altered expression of glycans is associated with cell-cell signal transduction and regulation of cell functions in the bone marrow micro-environment. Studies of this micro-environment often use two human bone marrow stromal cell lines, HS5 and HS27a, co-cultured with myeloid cells. We hypothesized that differential protein glycosylation between these two cell lines may contribute to functional differences in in vitro co-culture models. In this study, we applied an integrated strategy using genomic, proteomic, and functional glycomic techniques for global expression profiling of N-glycans and their related genes and enzymes in HS5 cells versus HS27a cells. HS5 cells had significantly enhanced levels of bisecting N-glycans (catalyzed by MGAT3 [β-1,4-mannosyl-glycoprotein 4-β-N-acetylglucosaminyltransferase]), whereas HS27a cells had enhanced levels of Galβ1,4GlcNAc (catalyzed by β4GalT1 [β4-galactosyltransferase I]). This integrated strategy provides useful information regarding the functional roles of glycans and their related glycogenes and glycosyltransferases in the bone marrow microenvironment, and a basis for future studies of crosstalk among stromal cells and myeloma cells in co-culture.


Cerebellar plaques in familial Alzheimer's disease (Gerstmann-Sträussler-Scheinker variant?).
A large kindred, with two brothers coming to autopsy, of a syndrome consisting of ataxia, dementia, and some Parkinsonian features is reported; inheritance appears to be autosomal dominant. Neuropathologically, there were plaques and neurofibrillary tangles in the cerebral cortex as well as some in the basal ganglia, particularly reminiscent of the plaques seen in Kuru; there was only minimal spinal cord disease (pyramidal tract field). The problems of classifying this condition--Alzheimer's disease with cerebellar involvement or other entities, such as the Gerstmann-Sträussler-Scheinker condition (1936), especially now that transmission to animals in the latter has been reported--are discussed. Some relevant theoretical considerations derived from animal work, particularly in scrapie, are also reviewed.


Commercial fibrinogen, autogenous plasma, whole blood and cryoprecipitate for coagulum pyelolithotomy: a comparative study.
Coagulation pyelolithotomy provides an effective means to remove multiple calculi from the renal collecting system. The strength of the coagulum is directly proportional to the concentration of fibrinogen and inversely proportional to the concentration of thrombin. Because of the fear of hepatitis fibrinogen may soon be unavailable commercially. It will then become necessary to use plasma from the patient as the source of fibrinogen. By the process of cryoprecipitation fibrinogen levels can be increased about 10-fold, yielding clots of greater tensile strength than would be obtained from non-concentrated plasma.


Do perceptual expertise and implicit racial bias predict early face-sensitive ERP responses?
Studies examining the visual perception of face race have revealed mixed findings regarding the presence or direction of effects on early face-sensitive event-related potential (ERP) components. Few studies have examined how early ERP components are influenced by individual differences in bottom-up and top-down processes involved in face perception, and how such factors might interact to influence early face-sensitive ERP components has yet to be investigated. Thus, the current study examined whether P100, N170, and P200 responses can be predicted by individual differences in own- and other-race face recognition, implicit racial bias, and their interaction. Race effects were observed in the P100, N170, and P200 responses. Other-race face recognition, implicit racial biases, and their interaction explained a significant amount of unique variability in N170 responses when viewing other-race faces. Responses to own-race faces were minimally influenced with only implicit racial bias predicting a significant amount of unique variability in N170 latency when viewing own-race faces. Face recognition, implicit racial bias, or their interaction did not predict P100 responses. The current findings suggest that face recognition abilities and its interaction with implicit racial bias modulate the early stages of other-race face processing.


A reassessment of the expected development consequences of tsetse control efforts in Africa.
Since the World Food Conference (1974) recommended a long term program of tsetse control, increasing attention of governments and international agencies has focused on the problem. This paper briefly outlines the strategies potentially available for tsetse control operations before assessing the likely consequences of any large scale tsetse control endeavor. The implications for both natural and human systems are shown to be profound and, in many cases, counter-productive to development goals. Suggestions for more appropriate strategies of addressing the tsetse issue are included. The major conclusions of the study are: (1) extreme caution is needed in relating the absence of development to the presence of the tsetse fly; (2) promises of benefits forthcoming with the removal of the tsetse fly must be viewed with skepticism; (3) in some cases a case can be made for retaining the tsetse; (4) fly zone problems can be addressed in many ways other than tsetse removal; (5) the regions most likely to incorporate successful tsetse control efforts will be on the margins of tsetse range, removed from border areas beyond the purvey of tsetse control efforts and within the domain of a stable administrative structure capable of mobilizing planning, funding and personnel; (6) it is important to define the targeted human population for the designed development benefits. Different strategies should be employed in virgin lands, places with people lacking livestock experience and places intended for expanding pastoralist rangelands; (7) the push for tsetse eradication arises from its role as a disease vector, its 'non-political' status as a development target and the strong Western bias toward the role of cattle in the modern agricultural mix.


Flexible Terahertz Metamaterial Biosensor for Ultra-Sensitive Detection of Hepatitis B Viral DNA Based on the Metal-Enhanced Sandwich Assay.
The high sensitivity and specificity of terahertz (THz) biosensing are both promising and challenging in DNA sample detection. This study produced and refined a flexible THz MM biosensor for ultrasensitive detection of HBV in clinical serum samples based on a gold magnetic nanoparticle-mediated rolling circle amplification (GMNPs@RCA) sandwich assay under isothermal conditions. Typically, solid-phase RCA reactions mediated by circular padlock probes (PLPs) are triggered under isothermal conditions in the presence of HBV DNA, resulting in long single-stranded DNA (ssDNA) with high fidelity and specificity. Then, the resultant ssDNA was conjugated with detection probes (DPs) immobilized on gold nanoparticles (DP@AuNPs) to form GMNPs-RCA-AuNPs sandwich complexes. The HBV DNA concentrations were quantified by introducing GMNPs-RCA-AuNPs complexes into the metasurface of a flexible THz metamaterial-based biosensor chip and resulting in a red shift of the resonance peak of the THz metamaterials. This biosensor can lead to highly specific and sensitive detection with one-base mismatch discrimination and a limit of detection (LOD) down to 1.27E + 02 IU/ml of HBV DNA from clinical serum samples. The HBV DNA concentration was linearly correlated with the frequency shift of the THz metamaterials within the range of 1.27E + 02∼1.27E + 07 IU/ml, illustrating the applicability and accuracy of our assay in real clinical samples. This strategy constitutes a promising THz sensing method to identify virus DNA. In the future, it is hoped it can assist with pathogen identification and clinical diagnosis.


Molecular genetics of alpha 2 plasmin inhibitor.
Analysis of the cDNA for alpha 2PI and its expression experiment indicated that the leader sequence is pre-pro peptide containing an N-terminal hydrophobic prepeptide (signal sequence) of 27 amino acids, followed by a hydrophilic propeptide of 12 amino acids. The alpha 2PI gene contains 10 exons and 9 introns distributed over approximately 16 kilobases of DNA. Two families of hereditary alpha 2PI deficiency were found to have changes of nucleotide sequence in an exon coding for plasma alpha 2PI, resulting in productions of variant proteins. These proteins are mostly retained within the cells, resulting in a deficiency of alpha 2PI in a circulating blood plasma.


Regulation of lipid-droplet transport by the perilipin homolog LSD2.
Motor-driven transport along microtubules is a primary mechanism for moving and positioning organelles. How such transport is regulated remains poorly understood. For lipid droplets in Drosophila embryos, three distinct phases of transport can be distinguished. To identify factors regulating this transport, we biochemically purified droplets from individual phases and used 2D gel analysis to search for proteins whose amount on droplets changes as motion changes. By mass spectrometry, we identified one such protein as LSD2. Similar to its mammalian counterpart Perilipin, LSD2 is responsible for regulating lipid homeostasis. Using specific antibodies, we confirmed that LSD2 is present on embryonic lipid droplets. We find that lack of LSD2 causes a specific transport defect: Droplet distribution fails to undergo the dramatic changes characteristic of the wild-type. This defect is not due to a complete failure of the core transport machinery--individual droplets still move bidirectionally along microtubules with approximately normal velocities and kinetics. Rather, detailed biophysical analysis suggests that developmental control of droplet motion is lost. We show that LSD2 is multiply phosphorylated in a developmentally controlled manner. LSD2 phosphorylation depends on the transacting signal Halo, and LSD2 can physically interact with the lipid-droplet-associated coordinator Klar, identifying LSD2 as a central player in the mechanisms that control droplet motion. LSD2 appears to represent a new class of regulators, a protein that transduces regulatory signals to a separable core motor machinery. In addition, the demonstration that LSD2 regulates both transport and lipid metabolism suggests a link between lipid-droplet motion and lipid homeostasis.


Comparative Study of Percutaneous Dilatational Tracheostomy and Conventional Surgical Tracheostomy in Critically Ill Adult Patients.
The present study was aimed to compare percutaneous dilatational tracheostomy (PDT) with that of conventional surgical tracheostomy (ST) in critically ill adult patients requiring tracheostomy for respiratory management. For this purpose 32 critically ill patients, admitted to the ICU between July 2016 and June 2018, were subjected to tracheostomy and randomly divided into two groups (PDT and ST) of 16 patients each. Mean duration of intubation was similar between the two procedures while the mean size of the tracheostomy tube was smaller in percutaneous technique. In comparison, post-operative infection after 7 days seem to be statistically lowered and the length of scar tend to be smaller in PDT patients. Although early and late post-operative complication rates are not statistically significant in the PDT groups, yet investigations of the long-term outcome following PDT are, therefore, necessary. Generally, PDT has lower acute complications than ST, although this may vary by the specific PDT technique. Patient factor may also influence complications. In view of the benefit versus risks in tracheostomy, PDT may be considered the "procedure of choice" for performing elective tracheostomies in critically ill adult patients.


The Effects of Lemon Balm (Melissa officinalis L.) Essential Oil on the Stress Response, Anti-Oxidative Ability, and Kidney Metabolism of Sea Bass during Live Transport.
This study was conducted to enhance the viability and alleviate the oxidative stress response using MO for sea bass during live transport. Six experimental groups were designed, and the effects of the physiological responses of MO were evaluated in comparison with MS-222 and eugenol. The physiological stress levels, proprotein convertase subtilisin/kexin type 9 (PCSK-9), antioxidant enzyme activities, and kidney parameters of blood serum were determined. It was found that cortisol level, glucose (Glu), lactic acid (LD), heat shock proteins (HSPs), catalase (CAT), myeloperoxidase (MPO), glutathione peroxidase (GSH-Px), uric acid (UA), and urea nitrogen (BUN) in the MO-treated samples were lower than that of the control (133.72 ng/L); however, the total antioxidant capacity (T-AOC) was higher after 72 h of the simulated live transport. The ability to resist oxidative stress increased along with the increase in the MO concentration in the water during live transport, which was similar to the results of MS-222 and eugenol treatment. In conclusion, MO, acting as a kind of novel sedative and anesthetic, can be used to improve the oxidative system and survival rate during live transport. The results of this study provide a reference for enhancing animal welfare and anti-oxidative stress ability, reducing mortality and the stress response during live fish transport.


Variations by layers and developmental changes in expression of telencephalin in the visual cortex of cat.
The expression of telencephalin in visual cortex of cat and monkey was studied immunohistochemically. In adult cats and monkeys, immunoreactivity to a polyclonal antibody raised against telencephalin was especially low in layer IV, which receives massive afferent input from the thalamus. In kitten visual cortex, the antibody bound both layer IV and other cortical layers during the most sensitive period for ocular dominance plasticity. Outside the sensitive period, the staining of layer IV was selectively reduced. These findings suggest that the expression of telencephalin is developmentally regulated during the early period and may play a role in regulating plasticity during the sensitive period.


Diseases in patients coming to a sleep center with symptoms related to restless legs syndrome.
To explore the profile of patients who visit a sleep center with symptoms that fulfill the four essential criteria for restless legs syndrome (RLS). A prospective study. Outpatients from one sleep disorders clinic in Taiwan. 1,200 consecutive patients visit sleep disorders clinic with any sleep complaints. After completing a history and physical examination, all participants answered the RLS questionnaire. Subjects who fulfilled the four essential criteria for RLS were referred to a special clinic. A work-up including blood tests, polysomnography, and specialized neurological tests etc. was performed to make the final diagnosis. A total of 1,185 participants were enrolled, and, of these, 131(11.1%) fulfilled the four essential criteria for RLS, and 121 completed the supplemental work-up. Their mean age was 47.6±13.3 and 52.9% were male. Insomnia and snoring were the most common chief complaints. Obstructive sleep apnea syndrome and other diseases were found in 103 patients. Only 18 (14.9%) patients had no comorbid condition and were diagnosed with primary RLS. Symptoms of RLS are common in patients with sleep complaints. Even in a sleep clinic, using a questionnaire approach for identification of RLS has a low positive predictive value. Clinicians should pay attention to the limitations of the 4-item questionnaire in diagnosis of RLS and also the importance of a careful differential diagnosis to identify possible secondary causes of RLS.


Glucosinolate Transporter1 involves in salt-induced jasmonate signaling and alleviates the repression of lateral root growth by salt in Arabidopsis.
Salt stress has negative impact on plant development and growth. Jasmonic acid (JA), a phytohormone, has been shown to involve in salt-induced inhibition of primary root growth. The Arabidopsis Glucosinolate transporter1 (GTR1/NPF2.10) is characterized as a JA-Ile, a bioactive form of JA, transporter. However, whether GTR1 participates in salt responses is not clear. In this study, we confirmed that GTR1 is induced by both JA and salinity. Salt-induced JA signaling is affected in gtr1 mutant. The JA responsive genes, JAZ1, JAZ5, MYC2, LOX3, are down-regulated in gtr1 mutant. Phenotypic analyses showed that the salinity-induced lateral root growth inhibition is enhanced in gtr1 mutant, suggesting that GTR1 plays a positive role in lateral root development under salt stress. Interestingly, the expression of a Na+ transporter, HKT1, is upregulated in gtr1. Since HKT1 is a negative regulator for lateral root development under salt stress, we proposed that GTR1 alleviates the repression of lateral root development by salt stress by mediating JA signaling and repressing HKT1 expression. This study demonstrates that GTR1 is the molecular link between salt stress, JA signaling, and lateral root development.


Post mortem time and season alter subpopulation characteristics of Iberian red deer epididymal sperm.
We have studied the effect of post mortem time and season on sperm subpopulation pattern and characteristics. We used epididymal samples from free-ranging Iberian red deers harvested during the hunting season. We studied samples at different moments of the year (rut, transition period and post-rut), and at different times post mortem (up to 4 days). Sperm were extracted from the cauda epididymis and their motility was evaluated by means of a CASA system. A principal component and clustering analysis were carried out to identify subpopulations. Post mortem time caused a significant decrease in motility quality, and a general deterioration in subpopulation characteristics. We found three subpopulations the first day, and the one indicating good sperm quality decreased with post mortem time until it disappeared on the fourth day. This may indicate considerable impairment of the samples after 72 h post mortem, which could compromise their use in AI programs. With regard to season, subpopulation pattern and characteristics were better in the transition and post-rut periods. Moreover, we found one subpopulation formed by mature spermatozoa, which increased from rut to post-rut. This might be a negative fact, because samples collected after the rut may undergo hypermaturation, which possibly impairs fertility. Our results are of interest for the management of wildlife germplasm banks based on post mortem sperm recovery.


Sarcoid granulomas of the skin produced by acrylic and nylon fibres.
The introduction into the skin of organic or inorganic substances can produce sarcoid-like granulomas. Two new granulomas of this type are described related to acrylic and nylon fibres. The aetiological diagnosis of such lesions can be confirmed by the identification of these synthetic materials within the-granuloma cells, using histochemical techniques used in the textile industry. An 'individual factor', probably immunological in nature, may be implicated.


Diagnosis and Management of Nephrolithiasis.
Nephrolithiasis is a common affliction, affecting approximately 10% of adults. Potentially presenting with acute abdominal or flank pain, nausea, or emesis, it may pose as a general surgical condition. Therefore, recognition, diagnosis, and management concerns are pertinent to the general surgeon. Furthermore, the risk of nephrolithiasis is increased in common general surgical conditions, including inflammatory bowel disease, hyperparathyroidism, and short gut. Nephrolithiasis may be induced as a result of general surgical interventions, including gastric bypass and bowel resection with ileostomy. An understanding of this common disease will improve coordination of patient care between urologists and general surgeons.


Community's perceived high risk of coronavirus infections during early phase of epidemics are significantly influenced by socio-demographic background, in Gondar City, Northwest Ethiopia: A cross-sectional -study.
Epidemiological studies during the early phase of the coronavirus (COVID-19) pandemics reported different level of people's risk perception in different countries. There is a paucity of data on perceived high risk of COVID-19 and associated factors in Ethiopia. We sought to assess the prevalence of community's perceived high risk about COVID-19 infections and associated factors among Gondar town community. A cross-sectional study was carried out from April 20 to 27, 2020 in Gondar town community, Northwest Ethiopia. Multistage cluster sampling technique was used to recruit 635 participants. Structured and pre-tested questionnaire was used to collect the data. Descriptive statistics, bivariate and multivariable binary logistic regression were used to summarize the results. A total of 623 participants were considered in the analysis with a response rate of 98.1%. The prevalence of coronavirus high risk perceptions of the respondents was found to be 23.11% (95% CI; 19.80%-26.43%). Age above 45 years (AOR = 1.41, 95%CI; 1.19-2.66), college and above educational level (AOR = 0.28, 95%CI; 0.21-0.98), and poor knowledge towards COVID-19 virus (AOR = 1.57, 95%CI; 1.09-2.23) were significantly associated with perceived high risk about COVID-19. The prevalence of perceived high risk of COVID-19 was found to be low. Factors such as age, educational status, and knowledge about COVID-19 virus were found to be independent predictors of perceived high risk towards COVID-19. Government and non-government organizations should use formal and informal means of educating the community.


Assessing physical access to healthy food across United Kingdom: A systematic review of measures and findings.
Existing research suggests that physical access to food can affect diet quality and thus obesity rates. When defining retail food environment (RFE) quantitatively, there is a little agreement on how to measure "lack of healthy food" and what parameters to use, resulting in a heterogeneity of study designs and outcome measures. In turn, this leads to a conflicting evidence base being one of the many barriers to using evidence in policy-making. This systematic review aimed to identify and describe methods used to assess food accessibility in the United Kingdom (UK) to overcome heterogeneity by providing a classification of measures. The literature search included electronic and manual searches of peer-reviewed literature and was restricted to studies published in English between January 2010 and March 2021. A total of 9365 articles were assessed for eligibility, of which 44 articles were included in the review. All included studies were analysed with regards to their main characteristics (e.g., associations between variables of interest, setting, sample, design, etc.) and definition of RFE and its metrics. When defining these metrics, the present review distinguishes between a point of origin (centroid, address) from which distance was calculated, summary statistic of accessibility (proximity, buffer, Kernel), and definition of distance (Euclidean, network distance). Trends, gaps and limitations are identified and recommendations made for food accessibility research in UK. Multiple theoretical and methodological constructs are currently used, mostly quantifying distance by means of Euclidean and ring-buffer distance, using both proximity- and density-based approaches, and ranging from absolute to relative measures. The association between RFE and diet and health in rural areas, as well as a spatiotemporal domain of food access, remains largely unaccounted. Evidence suggests that the duration of exposure may bear a greater importance than the level of exposure and that density-based measures may better capture RFE when compared with proximity-based measures, however, using more complex measures not necessarily produce better results. To move the field forward, studies have called for a greater focus on causality, individual access and the use of various measures, neighbourhood definitions and potential confounders to capture different aspects and dimensions of the RFE, which requires using univariate measures of accessibility and considering the overall context in terms of varying types of neighbourhoods. In order to render ongoing heterogeneity in measuring RFE, researchers should prioritise measures that may provide a more accurate and realistic account of people's lives and follow an intuitive approach based on convergence of results until consensus could be reached on using some useful standards.


Effectiveness and safety of kamikihito, a traditional Japanese medicine, in managing anxiety among female patients with intractable chronic constipation.
The prevalence of anxiety in patients with chronic constipation is particularly high and these individuals are not necessarily satisfied by normal treatments targeting the gastrointestinal tract. Kamikihito, a traditional Japanese Kampo medicine, has been widely used to date in treating anxiety and neurosis in Japan. We conducted a single-arm, open-label pilot study of female patients with intractable chronic constipation and anxiety who took kamikihito by mouth for 12 weeks. Validated symptom questionnaires on anxiety and gastrointestinal symptoms [the Profile of Mood States, second edition (POMS2); the State-Trait Anxiety Inventory (STAI); and the Gastrointestinal Symptom Rating Scale (GSRS)] were completed at each study visit. Plasma, salivary, and stool samples were also assessed to evaluate levels of clinical bioactive substances linked to stress and inflammation, oxidative levels, the metabolome profile, and gut microbiota. Twenty-four patients completed this study. Anxiety was significantly reduced at four and 12 weeks (Tension-Anxiety subscale of the POMS2, p = 0.006 and p = 0.039; Trait anxiety score of the STAI, p < 0.001 and p = 0.034), while the total GSRS score was improved at 12 weeks (p = 0.039). Targeted metabolomics in plasma showed significant alterations in some metabolites associated with psychological symptoms, such as O-phosphoethanolamine. No significant differences were found between pre- and posttreatment levels of clinical bioactive substances related to stress and inflammation, oxidative levels, and the gut microbiota in this cohort. No serious adverse events occurred. Kamikihito ameliorated psychological and gastrointestinal symptoms in patients with chronic constipation. In parallel with the onset of efficacy, kamikihito modulated some anxiety-related metabolites. Kamikihito was safe and well-tolerated.


Rational design to improve thermostability and specific activity of the truncated Fibrobacter succinogenes 1,3-1,4-β-D-glucanase.
1,3-1,4-β-D-Glucanase has been widely used as a feed additive to help non-ruminant animals digest plant fibers, with potential in increasing nutrition turnover rate and reducing sanitary problems. Engineering of enzymes for better thermostability is of great importance because it not only can broaden their industrial applications, but also facilitate exploring the mechanism of enzyme stability from structural point of view. To obtain enzyme with higher thermostability and specific activity, structure-based rational design was carried out in this study. Eleven mutants of Fibrobacter succinogenes 1,3-1,4-β-D-glucanase were constructed in attempt to improve the enzyme properties. In particular, the crude proteins expressed in Pichia pastoris were examined firstly to ensure that the protein productions meet the need for industrial fermentation. The crude protein of V18Y mutant showed a 2 °C increment of Tm and W203Y showed ∼30% increment of the specific activity. To further investigate the structure-function relationship, some mutants were expressed and purified from P. pastoris and Escherichia coli. Notably, the specific activity of purified W203Y which was expressed in E. coli was 63% higher than the wild-type protein. The double mutant V18Y/W203Y showed the same increments of Tm and specific activity as the single mutants did. When expressed and purified from E. coli, V18Y/W203Y showed similar pattern of thermostability increment and 75% higher specific activity. Furthermore, the apo-form and substrate complex structures of V18Y/W203Y were solved by X-ray crystallography. Analyzing protein structure of V18Y/W203Y helps elucidate how the mutations could enhance the protein stability and enzyme activity.


Barley RIC171 interacts with RACB in planta and supports entry of the powdery mildew fungus.
RHO-like GTPases of plants (ROPs, also called RACs) are involved in plant development and interaction with the environment. The barley ROP protein RACB is involved in susceptibility to the fungal pathogen Blumeria graminis f.sp. hordei (Bgh). By screening barley sequence databases for potential protein interactors of plant RHO-like proteins, we identified a ROP-interactive CRIB (CDC42/RAC interactive binding) motif containing protein of 171 amino acids (RIC171). The protein interacted with constitutively activated RACB in a targeted yeast two-hybrid assay. By use of split yellow fluorescing protein fusions, we demonstrated that RIC171 interacts with constitutively activated (CA) RACB-G15V but not with dominant negative RACB-T20N in planta. Transient overexpression of RIC171, similar to overexpression of CA RACB-G15V, rendered epidermal cells more susceptible to penetration by Bgh. In contrast, expression of a 46-amino-acid RIC171-CRIB peptide, which was sufficient to interact with CA RACB-G15V, had a dominant negative effect and reduced susceptibility to Bgh. A red fluorescing DsRED-RIC171 fusion protein colocalized with green fluorescing GFP-RACB-G15V at the cell periphery. Coexpression with CA RACB-G15V but not with RACB-T20N increased peripheral localization of DsRED-RIC171. Additionally, DsRED-RIC171 accumulated at sites of fungal attack, suggesting enhanced ROP activity at sites of attempted fungal penetration.


In utero galactose intoxication in animals.
To assess in utero effects of galactose, diets containing large amounts of the sugar have been fed to pregnant rats with examination of the fetuses and newborns. Galactose levels in fetal blood parallel those of the dam and amniotic fluid contains high concentrations of galactose and galactitol. In the offspring and in the fetuses cataracts, and a decrease in brain weight, protein content and DNA are observed. There is an elevated content of galactitol and decrease in myo-inositol in the brain of galactose-intoxicated newborns. Brain synaptosomes of young rats whose mothers were fed galactose show a reduced response in vitro to acetylcholine as evidenced by a decrease in incorporation of myo-inositol into phosphatidylinositol and an inappropriate change in phosphatidylinositol content. The data indicate that there can be significant effects in the offspring of pregnant rats fed a high galactose diet. The findings support the concept that in utero toxicity may occur in the human galactosemic fetus.


Role of levosimendan in sepsis and septic shock.
To present the pharmacologic and biologic profile of levosimendan and discuss potential indications in the treatment of sepsis and septic shock, with a special focus on myocardial and pulmonary dysfunction. In animal models of endotoxic shock, levosimendan improved both left ventricular systolic and diastolic dysfunction, as well as ventriculovascular coupling. In addition, positive effects have been reported on right ventricular performance and pulmonary circulation. Two randomized, controlled trials in patients with septic shock revealed levosimendan provided consistent beneficial effects on cardiopulmonary performance, global oxygen transport, splanchnic perfusion and renal function. These effects have been reported as superior to placebo and the classic inotropic agent dobutamine. Due to its vasodilatory effects, combination with vasoconstrictor agents may be crucial in the presence of arterial hypotension. There is increasing evidence that levosimendan exerts beneficial effects in the treatment of sepsis-induced myocardial and pulmonary dysfunction. Future large-scale multicenter clinical trials are now needed to clarify whether levosimendan improves the overall outcome of patients with sepsis and septic shock.


Influence of pregnancy on diurnal and seasonal changes in glucose level and activity of FDPA, AlAT and AspAT in mares.
1. The diurnal changes in the glucose level and in activity of FDPA, A1AT and AspAT in four pregnant standard-bred mares were studied. 2. As a control four barren mares, were kept and examined in the same conditions. 3. Blood samples were taken every 4 hr for one day, each month, throughout pregnancy, or one year. 4. A diurnal rhythm in activity of A1AT and AspAT in barren mares was found. The pregnancy masked diurnal rhythm in activities of both transaminases. 5. No diurnal rhythm in glucose level and FDPA activity in both groups of mares was observed. 6. Seasonal cyclicity was found in all indices studied, in both groups of mares. 7. The pregnancy did not abolish cyclicity in parameters studied but modified their behaviour--causing a shift of acrophases (glucose, FDPA, AspAT) and lowering the amplitudes (FDPA, A1AT, AspAT).


Up-regulation of [3H]DAMGO and [3H]DTLET opioid binding sites in laminae I-II of the spinal cord in intact and deafferented morphine-tolerant rats.
Using quantitative autoradiography and selective opioid ligands, we have measured the effects of morphine-induced tolerance on [3H]DAMGO and [3H]DTLET binding sites in the superficial spinal dorsal horn (laminae I-II) of intact and deafferented rats (unilateral C4-T2 dorsal rhizotomy). In intact rats, the treatment induced an up-regulation of 26% and 39% for [3H]DAMGO and [3H]DTLET binding sites, respectively, without modification of receptor affinity. In deafferented rats, the treatment similarly induced an up-regulation of 31% and 29% for [3H]DAMGO and [3H]DTLET binding sites, respectively, on the contralateral side, and of 21% and 25%, respectively, on the ipsilateral side. These data demonstrate that the up-regulation induced by morphine tolerance is of similar magnitude for both presynaptic (on primary afferent fibers) and postsynaptic (on spinal neurons) opioid binding sites in the rat dorsal horn.


[Universal immunisation against influenza in paediatrics, yes or no?].
The recommendations on influenza vaccination are not homogeneous between countries, with striking differences between the current recommendations in United States and Europe. The objective of the study is to determine the efficacy, effectiveness and safety of the current flu vaccine (trivalent inactivated vaccine and adapted to the cold [LAIV] live virus vaccine) in healthy children, and to try and answer the following question: universal immunization against influenza in Paediatrics, yes or no? A scheme of work based on the five standard steps of evidence or science-based medicine was used: 1) question, 2) search, 3) valuation, 4) applicability and 5) adequacy. Nine systematic reviews, published between 2005 and 2012, were selected that answered our clinical question, and which included the best available information (randomised clinical trials, cohort studies and case studies). The flu vaccine in childhood has the right cost - benefit - risk relationship. In all systematic reviews the efficacy of the flu vaccine varied between 58%-65%, and effectiveness between 28%-61%. Both efficacy and effectiveness increase with age, and there are limited studies showing sufficient evidence in children < 2 years. There are further areas to develop: more and better clinical trials on influenza vaccines in infants from 6 to 23 months; further research to achieve better influenza vaccines (addition of adjuvants, higher doses in children between 6 and 23 months, and study the LAIV vaccine in children between 6 and 23 months); and improvement in the prediction of vaccine strains responsible for the outbreak.


Detection of high-grade stenoses with multislice computed tomography in heart transplant patients.
Post-transplant follow-up of heart transplant patients consists of repeated coronary angiography, which is associated with high costs, discomfort and risk. We sought to determine whether multislice computed tomography (MSCT) permits the exclusion or progression of coronary artery disease in heart transplant patients. MSCT scanning (Philips CT MX 8000 IDT) and invasive coronary angiography were performed on 66 consecutive heart transplant patients. One hundred milliliters of non-ionic iodinated contrast medium was applied for CT angiography. For MSCT analysis, coronary arteries and side branches with a diameter > or =1.5 mm were assessed for the presence of luminal narrowing of >70%. MSCT results were compared with those of quantitative coronary angiography analysis. Ten patients (17%) had one significant stenosis, whereas 3 patients (5%) had 2-vessel disease and none had 3-vessel disease. MSCT was performed successfully on 60 patients enrolled in our analysis. Forty-two of 44 patients (95%) who were estimated to be fully evaluable for MSCT were correctly classified. On per-segment-based analysis, sensitivity, specificity and positive and negative predictive values were 59%, 94%, 91% and 99.43%, respectively. After exclusion of unevaluable segments, sensitivity and specificity increased to 71% and 99.86%, respectively. On per-patient-based analysis, sensitivity, specificity and positive and negative predictive values were 88%, 97%, 88% and 97%, respectively, in evaluable transplant recipients. MSCT with its high specificity and high negative predictive value allows the exclusion of significant coronary artery vasculopathy in evaluable patients. From the clinical point of view, this might spare additional invasive coronary angiography in heart transplant patients.


Based on the synergistic effect of Mg2+ and antibacterial peptides to improve the corrosion resistance, antibacterial ability and osteogenic activity of magnesium-based degradable metals.
To overcome the restricted degradation, poor antiacterial and osteoindctive problems of magnesium and its alloys, this study presented the spinning coating of an antimicrobial peptide (AP)-loaded silk fibroin (SF) composite onto a corrosion-resistant MgO-coated AZ31 Mg alloy via anodization (aMgO) and electrodeposition (eMgO) methods. The composite coatings not only created a smooth and hydrophilic surface, but also obviously improved the corrosion resistance according to the test of corrosion potential and current density. The colonization of E. coli on MgO-AP composite coatings was significantly reduced as compared to the MgO layers, due to the potential synergetic effects of APs and Mg2+. Compared with the bare AZ31, the composite coating inhibited the corrosion of the substrate and the release of Mg2+, supported the adhesion, spreading and proliferation of osteoblasts, and presented a significantly improved osteogenic differentiation trend. Therefore, the MgO-AP composite coating, which had both antibacterial and bone-promoting abilities, was expected to be applied for surface modification of magnesium alloy implants to solve the clinical problems of bacterial infection and poor osseointegration.


Mathematical Biology: Expand, Expose, and Educate!
Mathematical biology has made significant contributions and advancements in the biological sciences. Recruitment efforts focus on encouraging students, especially those who are underrepresented and underserved, to pursue the field of mathematical biology, regardless of their undergraduate institution type, and raise awareness about the countless professional and academic possibilities provided by this specialized training. This article examines the need to expand, expose, and educate others about mathematical biology. To support field expansion, we give several recommendations of ways to integrate mathematics applied curricula to attract broader student interest. With this exposure-whether it is led by an individual, a department, a university, or researchers in mathematical biology-each can help to promote a base knowledge and appreciation of the field. In order to encourage the next generation of researchers to consider mathematical biology, we highlight current interdisciplinary programs, share popular mathematical tools, and present some thoughts on ways to support a thriving and inclusive mathematical biology community for years to come.


Non-stressful death of 23S rRNA mutant G2061C defective in puromycin reaction.
Catalysis of peptide bond formation in the peptidyl transferase center is a major enzymatic activity of the ribosome. Mutations limiting peptidyl transferase activity are mostly lethal. However, cellular processes triggered by peptidyl transferase deficiency in the bacterial cell are largely unknown. Here we report a study of the lethal G2061C mutant of Escherichia coli 23S ribosomal RNA (rRNA). The G2061C mutation completely impaired the puromycin reaction and abolished formation of the active firefly luciferase in an in vitro translation system, while poly(U)- and short synthetic mRNA-directed peptidyl transferase reaction with aminoacylated tRNAs in vitro was seemingly unaffected. Study of the cellular proteome upon expression of the 23S rRNA gene carrying the G2061C mutation compared to cells expressing wild-type 23S rRNA gene revealed substantial differences. Most of the observed effects in the mutant were associated with reduced expression of stress response proteins and particularly proteins associated with the ppGpp-mediated stringent response.


Younger Than 55 Years Old and BRAF V600E Mutation are Risk Factors for Lymph Node Metastasis in Papillary Thyroid Carcinomas ≤1.0 cm but Not in >1.0 cm.
Studies on the relationship between BRAF V600E mutation and the clinicopathologic features of papillary thyroid carcinoma (PTC), risk of lymph node metastasis in papillary thyroid microcarcinoma (PTMC) have shown inconsistent results. In this retrospective analysis, clinicopathological data of the patients were collected, and molecular testing was done for BRAF V600E mutation. PTC patients are divided into PTC≤1.0cm (PTMC) and PTC>1.0cm, and the relationship between BRAF V600E mutation and clinicopathologic features was analyzed respectively. Of the 520 PTC patients, 432 (83.1%) were female and 416 (80.0%) were <55 years old. BRAF V600E mutation was detected in 422 (81.2%) tumour samples of PTC. There was no significant difference in the frequency of BRAF V600E mutation between different age groups. There were 250 (48.1%) patients with PTMC and 270 (51.9%) patients with PTC>1.0cm. BRAF V600E mutation was significantly associated with bilateral cancer (23.0% vs 4.9%, P=0.005) and lymph node metastasis (61.7% vs 39.0%, P=0.009) in PTMC patients, while BRAF V600E mutation was significantly associated with bilateral cancer (24.9% vs 12.3%, P=0.048) in PTC>1.0cm patients. Logistic regression analysis showed that, after adjusting for gender, Hashimoto's thyroiditis and calcification, we found that younger age (<55 years old) (OR: 2.384, 95% CI: 1.241-4.579, P=0.009) and BRAF V600E mutation (OR: 2.213, 95% CI: 1.085-4.512, P=0.029) were significantly associated with lymph node metastasis in PTMC, similar results were not obtained in PTC>1.0cm. Younger age (<55 years old) and BRAF V600E mutation was independent risk factor for lymph node metastasis in PTMC.


School-based supervised therapy programs to improve asthma outcomes: current perspectives.
Asthma is one of the most common chronic diseases of childhood affecting 6.2 million (8.4%) children (<18 years old) in the USA. Asthma is also a leading cause of school absenteeism. Daily administration of preventive asthma medications improves asthma control. However, poor medication adherence is one of the barriers in achieving improved asthma outcomes. School-based supervised asthma therapy programs have been implemented to address this barrier. To conduct a review of the literature on school-based supervised asthma therapy interventions and the effect on outcomes in children with persistent asthma. We conducted a literature search using electronic search engines (ie, PubMed and Cochrane) and combinations of different search terms "school-based asthma," "school-based asthma therapy," and "school-based supervised asthma therapy." Inclusion criteria were school-based interventions with supervised asthma medication administration conducted in the USA, measuring asthma outcomes. From 443 titles and abstracts, 9 studies met the inclusion criteria. School-based interventions with supervised asthma medication administration revealed improvement in asthma outcomes, including improved medication adherence, increased symptom-free days, decreased daytime and nighttime symptoms, decreased use of rescue medication, decreased asthma-related health care utilization, fewer exacerbations requiring treatment with prednisone, decreased school absenteeism due to asthma, fewer days of activity limitation, improved quality of life, and improvement in both pulmonary inflammatory markers and peak flow readings. Our literature review demonstrated that school-based supervised asthma therapy improves asthma outcomes in urban children with persistent asthma. Schools are an ideal setting for implementation of asthma interventions for children and adolescents.


A Systematic Review and Meta-Analysis of Injection Site Reactions in Randomized-Controlled Trials of Biologic Injections.
Biologic agents are emerging as an important treatment option for immune-mediated diseases. Injection site reactions following subcutaneous injection of biologic agents is not well described in the literature. To summarize injection site reaction data in phase 3 trials of all biologic agents. MEDLINE, Embase, and CENTRAL databases were systematically searched on February 8, 2022. Proportional meta-analysis was conducted to summarize injection site reaction prevalence for each biologic. There were 158 articles included in the review. The most common types of injection site reactions were erythema (42.8%), unspecified reaction (23.3%), pain (12.4%), and pruritus (5.7%). No patients discontinued their treatment due to injection site reactions in 39 of the 48 studies that reported on discontinuation data. There were 16 biologics included in meta-analysis across 80 eligible studies. The biologics with the highest point prevalence of patients reporting injection site reactions were Canakinumab (15.5%; 294 patients), Dupilumab (11.4%; 1888 patients), Etanercept (11.4%; 4363 patients), and Ixekizumab (11.2%; 2205 patients). The biologics with the lowest point prevalence of injection site reactions were Risankizumab (0.8%; 707 patients), Brodalumab (1.3%; 1365 patients), Guselkumab (1.3%; 1852 patients), Secukinumab (1.9%; 1277 patients). The prevalence of injection site reaction in response to biologics ranges from 0.08 to 15.5%. Canakinumab, Dupilumab, Etanercept, and Ixekizumab had the highest prevalence of injection site reactions. Risankizumab, Brodalumab, Guselkumab, and Secukinumab had the lowest prevalence of injection site reactions. Recommendations are made regarding the improvement of adverse event reporting to better understand the epidemiology of injection site reactions.


Clinical significance of low expression of Prostasin mRNA in human gastric cancer.
Prostasin is considered to have suppressive activities against tumor progression. The aim of this study was to clarify its clinical significance in gastric cancer. Tumor and the corresponding normal samples were prepared from a total of 108 gastric cancer patients. Prostasin expression was assayed by real time reverse transcription (RT)-polymerase chain reaction (PCR) and by immunohistochemistry. Epigenetic silencing of the expression was examined by demethylation treatment. Survival was examined in Kaplan-Meier plots, and the relationship between its expression and clinicopathologic factors was statistically analyzed. Prostasin mRNA expression was significantly down-regulated in tumor tissues. Immunohistochemistry confirmed loss of Prostasin expression in gastric cancer. Gastric cancer cell lines that did not express Prostasin mRNA retrieved its expression following demethylation treatment. In those patients whose tumor expressed Prostasin mRNA at reduced levels, we observed shorter survival (P = 0.0110), due to a higher incidence of lymph node metastasis (P = 0.0087), lymphatic permeation (P = 0.0542) and venous permeation (P = 0.0492). Prostasin mRNA expression was frequently down-regulated in gastric cancer. Loss of expression might be regulated by epigenetic factors, contributing to the shorter survival. Reduced Prostasin mRNA expression might be a novel indicator for biological aggressiveness in gastric cancer.


Role of mitogen-activated protein kinases in tauroursodeoxycholic acid-induced bile formation in cholestatic rat liver.
Ursodeoxycholic acid exerts anticholestatic effects in various cholestatic disorders and experimental models of cholestasis. Its taurine conjugate (TUDCA) stimulates bile salt secretion in isolated perfused rat livers (IPRL) under physiological, non-cholestatic conditions, in part by mitogen-activated protein kinase (MAPK)-dependent mechanisms. The role of MAPK in the anticholestatic effect of TUDCA, however, is unclear. Therefore, we studied the role of MAPK in the anticholestatic effect of TUDCA in IPRL and isolated rat hepatocytes (IRH) in taurolithocholic acid (TLCA)-induced cholestasis. Bile flow, biliary levels of 2,4-dinitrophenyl-S-glutathione (GS-DNP) as a marker of hepatobiliary organic anion secretion and activity of lactate dehydrogenase (LDH) in hepatovenous effluate as a marker of hepatocellular damage in IPRL perfused with TUDCA and/or TLCA were determined in the presence or absence of MAPK inhibitors. In addition, phosphorylation of Erk 1/2 and p38(MAPK) induced by TUDCA and/or TLCA was studied by Western immunoblot in IPRL and IRH. TUDCA-induced bile flow was impaired by the Erk 1/2 inhibitor PD98059 in normal livers (-28%), but not in livers made cholestatic by TLCA. GS-DNP secretion was unaffected by PD98059 under both conditions. TUDCA-induced bile formation and organic anion secretion both in the presence and absence of TLCA were unaffected by the p38(MAPK) inhibitor SB202190. Erk 1/2 phosphorylation in liver tissue was unchanged after bile salt exposure for 70 min, but was transiently enhanced by TUDCA in IRH. MAPK do not mediate the anticholestatic effects of TUDCA in TLCA-induced cholestasis.


Invited Commentary: Comparing Approaches to Measuring Structural Racism.
In their article, Adkins-Jackson et al. (Am J Epidemiol. 2022;191(4):539-547) provide much needed insight on current approaches and challenges to epidemiologic research on structural racism. The authors encourage researchers to consider how structural racism is conceptualized in extant and future work, and whether existing measures accurately reflect the multidimensional nature of structural racism. In the spirit of continuing this conversation, I expand upon approaches to measuring structural racism. I compare the merits and challenges of scales, indexes, indicators, and policy-based measures of structural racism for use in epidemiologic research.


Clinical and nutritional outcomes after intestinal autotransplantation.
This study describes the operative techniques and early clinical and nutritional outcomes after intestinal autotransplantation (IATx). IATx is a novel surgical strategy for patients with abdominal neoplasms involving the root of the superior mesenteric and/or celiac arteries, but the effects of IATx on clinical and nutritional outcomes are not well-known. Six patients aged 24-67 years (mean, 54) underwent consecutive IATx in our center from January 2011 to January 2015. In all patients, selection and harvesting of a segmental autograft of bowel was carried out first, and radical en bloc resection of the neoplasm was performed second. One patient lost the autograft owing to arterial thrombosis 48 hours postoperatively, and another succumbed to a pancreatic fistula at 21 days. The remaining 4 patients survived with no evidence of tumor recurrence currently at 9-, 23-, 23-, and 39-months of follow-up. These 4 patients have had well-functioning autografts and have not required any intravenous fluid hydration since discharge. Serum d-xylose levels recovered fully 2 weeks postoperatively, and plasma proteins and cholesterol levels normalized 12-18 months later. The surviving 4 patients gained body weight without major alterations in lifestyle, work habits, or psychosocial conditions. Although IATx is associated with considerable operative risk, this aggressive approach allows patients with selected abdominal neoplasms involving the major mesenteric vessels to be completely resected and attain early intestinal autonomy from parenteral nutrition.


Generation and functional analysis of zinc finger nucleases.
The recent development of artificial endonucleases with tailored specificities has opened the door for a wide range of new applications, including the correction of mutated genes directly in the chromosome. This kind of gene therapy is based on homologous recombination, which can be stimulated by the creation of a targeted DNA double-strand break (DSB) near the site of the desired recombination event. Artificial nucleases containing zinc finger DNA-binding domains have provided important proofs of concept, showing that inserting a DSB in the target locus leads to gene correction frequencies of 1-18% in human cells. In this paper, we describe how zinc finger nucleases are assembled by polymerase chain reaction (PCR) and present two methods to assess these custom nucleases quickly in vitro and in a cell-based recombination assay.


Excessive activation of matrix metalloproteinases coincides with left ventricular remodeling during transition from hypertrophy to heart failure in hypertensive rats.
We sought to elucidate how the local activation of matrix metalloproteinases (MMPs) is balanced by that of the endogenous tissue inhibitors of MMP (TIMPs) during left ventricular (LV) remodeling. Although it is known that the extracellular matrix (ECM) must be altered during LV remodeling, its local regulation has not been fully elucidated. In Dahl salt-sensitive rats with hypertension, in which a stage of concentric, compensated left ventricular hypertrophy (LVH) at 11 weeks is followed by a distinct stage of congestive heart failure (CHF) with LV enlargement and dysfunction at 17 weeks, we determined protein and messenger ribonucleic acid (mRNA) levels of LV myocardial TIMP-2 and -4 and MMP-2, as well as their concomitant activities. No changes were found at the LVH stage. However, during the transition to CHF, TIMP-2 and -4 activities, protein and mRNA levels were all sharply increased. At the same time, the MMP-2 mRNA and protein levels and activities, as determined by gelatin zymography, as well as by an antibody capture assay, showed a substantial increase during the transition to CHF. The net MMP activities were closely related to increases in LV diameter (r = 0.763) and to systolic wall stress (r = 0.858) in vivo. Both TIMPs and MMP-2 remained inactive during hypertrophy, per se; they were activated during the transition to CHF. At this time, the activation of MMP-2 surpassed that of TIMPs, possibly resulting in ECM breakdown and progression of LV enlargement.


Bjcul, a snake venom lectin, modulates monocyte-derived macrophages to a pro-inflammatory profile in vitro.
Macrophages are cells of high plasticity and can act in different ways to ensure that the appropriate immune response remains controlled. This study shows the effects of the C-type Bothrops jararacussu venom lectin (BJcuL) on the activation of human macrophages derived from the U937 cell line. BJcuL binds on the cell surface, and this event is inhibited by its specific carbohydrate. It induced phagocytosis and production of H2O2, and expression of antigen presentation molecules. It also enhanced the production of TNF-α, GM-CSF and IL-6 by macrophages and indirectly induced T cells to an increased production of TNF-α, IFN-γ and IL-6 in the presence of LPS. Our results suggest that BJcuL can modulate macrophage functional activation towards an M1 state.


Effects of exercise training on glycaemic control in youths with type 1 diabetes: A systematic review and meta-analysis of randomised controlled trials.
The aim of the study is to evaluate whether exercise interventions are associated with improved glycaemic control in children and adolescents with type 1 diabetes mellitus (T1DM), and to examine its relationship with the characteristics of the intervention (i.e. type, intensity, length, and duration of the sessions). Eligible criteria were randomised controlled trials of youth aged 6-18 years with T1DM, participating in an exercise-based intervention where glycaemic control is measured (i.e. glycated haemoglobin [HbA1c]). Pooled effect sizes (Hedges'g) were calculated using random-effects inverse-variance analyses. Fourteen studies enrolling 509 patients were analysed. Effect size was expressed as Hedges' g to correct for possible small sample bias. Overall, HbA1c levels in the exercise group (g = -0.38 95% confidence interval [CI], -0.66 to -0.11; mean difference [MD] = -0.62%) were reduced compared with the control group. Concurrent training (g = -0.63 95%CI, -1.05 to -0.21), high-intensity exercise (g = -0.43 95%CI, -0.83 to -0.03), interventions ≥24 weeks (g = -0.92 95%CI, -1.44 to -0.40), and sessions ≥60 minutes (g = -0.71 95%CI, -1.05 to -0.08) showed larger changes (MD = -0.66% to 1.30%). In conclusion, our study suggests that programmes longer than 24 weeks with at least 60 min/session of high-intensity concurrent exercise may serve as a supportive therapy to metabolic control in youth with T1DM.HighlightsExercise training has a moderate effect on the reduction of glycated haemoglobin (HbA1c) and insulin dose per day in youths with type 1 diabetes.Exercise training moderately increases cardiorespiratory fitness youths with type 1 diabetes.Reductions in HbA1c are stronger with high-intensity and concurrent training (i.e. aerobic and strength) interventions, and longer programmes.


Scopolamine impairs auditory delayed matching-to-sample performance in monkeys.
Information concerning the major neurotransmitters critical for auditory memory is sparse. One possibility is the cholinergic system, important for performance in some tasks requiring visual short-term memory and attention [T.G. Aigner, M. Mishkin, The effects of physostigmine and scopolamine on recognition memory in monkeys, Behav. Neural. Biol. 45 (1986) 81-87; N. Hironaka, K. Ando, Effects of cholinergic drugs on scopolamine-induced memory impairment in rhesus monkeys, Jpn. J. Psychopharmacol. 16 (1996) 103-108; T.M. Myers, G. Galbicka, M.L. Sipos, S. Varadi, J.L. Oubre, M.G. Clark, Effects of anticholinergics on serial-probe recognition accuracy of rhesus macaques (Macaca mulatta), Pharmacol. Biochem. Behav. 73 (2002) 829-834; H. Ogura, T.G. Aigner, MK-801 Impairs recognition memory in rhesus monkeys: comparison with cholinergic drugs, J. Pharmacol. Exp. Ther. 266 (1993) 60-64; D.M. Penetar, J.H. McDonough Jr., Effects of cholinergic drugs on delayed match-to-sample performance of rhesus monkeys, Pharmacol. Biochem. Behav. 19 (1983) 963-967; M.A. Taffe, M.R. Weed, L.H. Gold, Scopolamine alters rhesus monkey performance on a novel neuropsychological test battery, Cogn. Brain Res. 8 (1999) 203-212]. Five rhesus monkeys were trained to perform an auditory go/no-go delayed matching-to-sample (DMTS) task wherein two acoustic stimuli (500ms), separated by variable memory delays (500ms, 2500ms, or 5000ms), were either identical sound presentations, i.e., match trials, or two different sound presentations, i.e., nonmatch trials. Sound stimuli were chosen semi-randomly from a large set sound set ( approximately 900). After reaching a criterion of 80% correct on the behavioral task, monkeys were injected with saline or doses of scopolamine hydrochloride mixed in saline (3 microg, 5 microg, and 10 microg per 1kg of weight), 30 min before training. Scopolamine impaired performance accuracy on match trials in a dose-dependent manner. Blocking muscarinic receptors with scopolamine did not significantly impair motor responses, food motivation, or responses to rewarded sound. These findings support the hypothesis that the cholinergic system is important for auditory short-term memory.


Regulation of the p38 mitogen-activated protein kinase and dual-specificity phosphatase 1 feedback loop modulates the induction of interleukin 6 and 8 in cells infected with coronavirus infectious bronchitis virus.
Induction of pro-inflammatory response is a crucial cellular process that detects and controls the invading viruses at early stages of the infection. Along with other innate immunity, this nonspecific response would either clear the invading viruses or allow the adaptive immune system to establish an effective antiviral response at late stages of the infection. The objective of this study was to characterize cellular mechanisms exploited by coronavirus infectious bronchitis virus (IBV) to regulate the induction of two pro-inflammatory cytokines, interleukin (IL)-6 and IL-8, at the transcriptional level. The results showed that IBV infection of cultured human and animal cells activated the p38 mitogen-activated protein kinase (MAPK) pathway and induced the expression of IL-6 and IL-8. Meanwhile, IBV has developed a strategy to counteract the induction of IL-6 and IL-8 by inducing the expression of dual-specificity phosphatase 1 (DUSP1), a negative regulator of the p38 MAPK, in order to limit the production of an excessive amount of IL-6 and IL-8 in the infected cells. As activation of the p38 MAPK pathway and induction of IL-6 and IL-8 may have multiple pathogenic effects on the whole host as well as on individual infected cells, regulation of the p38 MAPK and DUSP1 feedback loop by IBV may modulate the pathogenesis of the virus.