Myelin protein zero mutation His39Pro: hereditary motor and sensory neuropathy with variable onset, hearing loss, restless legs and multiple sclerosis.
Mutations of myelin protein zero (MPZ) may cause inherited neuropathy with variable expression. To report phenotypic variability in a large American kindred with MPZ mutation His39Pro. Genetic testing was performed on 77 family members and 200 controls. Clinical and electrophysiological field study assessments were available for review in 47 family members. His39Pro was found in all 10 individuals prospectively identified with neuropathy. 200 normal controls were without mutation. Symptoms of neuropathy began in adulthood and were slowly progressive except for one acute-onset painful sensory neuropathy. Associated features included premature hearing loss (n = 7), nocturnal restless leg symptoms (n = 8) and multiple sclerosis in one. MPZ mutation His39Pro may be associated with acute-onset neuropathy, early-onset hearing loss and restless legs. The relationship with multiple sclerosis in the proband remains uncertain.


[Radiological findings in Currarino syndrome].
To describe the clinical, radiological and genetic findings of a family affected by Currarino syndrome (CS) (agenesis of the sacrum, presacral mass, and anal-rectal anomalies), and to familiarise the radiologist with this condition that, although uncommon, could be suspected by its characteristic images. A study was made of 8 out of 9 family members (the parents, 7 siblings; 4 males and 3 females) suspected of having CS. The clinical and genetic findings are described. Using simple X-rays, ultrasound and magnetic resonance imaging, the presence of agenesis of the sacrum, a presacral mass and anal-rectal anomalies were investigated. Furthermore, a genetic analysis of the HLBX9 gene was performed. Permission by the Ethics Committee was not requested as all the family members gave their consent by signing a document. The mother with a scimitar-shaped sacrum confirmed that she was the transmitter of the genetic mutation. One of the seven siblings had complete CS (sacral agenesis, anorectal stenosis, and anterior meningocele). Four siblings had an incomplete CS: 3 with sacral agenesis and a presacral mass (two anterior meningoceles and one teratoma) and the fourth with sacral agenesis and anorectal stenosis. One sibling had no anomalies. The mother, as well as four siblings, did not have the HLXB9 gene mutation. When there is sacral agenesis, the possibility of presacral masses and anorectal changes should be investigated. Likewise, if there is familial association, they should be investigated for a CS.


[In vitro investigation on the mechanism of cyclooxygenase-2 upregulation induced by spleen tyrosine kinase-nuclear factor κB signaling in cancer pain caused by oral cancer-associated macrophage].
This study explores the mechanism of cyclooxygenase-2 (COX-2) upregulation in oral cancers associated with macrophage by using molecular biology techniques and primary culture of murine macrophage. Murine macrophage was induced by macrophage colony-stimulating factor (M-CSF) and Cal27 conditional medium (CM). Purity of the macrophage was detected through CD68 immunofluorescence staining. Inhibitors of spleen tyrosine kinase (Syk) and nuclear factor κB (NFκB) were used to inhibit these pathways. In addition, real-time polymerase chain reaction and Western blot analysis were used to detect alterations in COX-2 and pathway-related proteins. All of the induced cells specifically expressed CD68. Cal27 CM could significantly induce COX-2 expression (P<0.001). Moreover, inhibition of Syk pathway attenuated NFκB-P65 phosphorylation and reduced COX-2 expression (P<0.01), and inhibition of NFκB pathway exerted no effects on Syk phosphorylation but significantly inhibited COX-2 upregulation (P<0.01). Syk-NFκB is responsible for COX-2 overexpression in oral cancer associated with macrophages. Targeting this pathway is possibly a new approach to control oral cancer-related pain. .


Myocardial imaging and radionuclide angiography in survivors of sudden cardiac death due to to ventricular fibrillation: preliminary report.
Twenty-one long-term survivors of out of hospital sudden cardiac death due to ventricular fibrillation underwent radionuclide angiography and myocardial imaging with thallium-201. In 13 patients images were obtained at rest and after maximal treadmill exercise; 11 of these 13 (85 percent) had an image defect in one or both studies. Eleven of the 21 patients (52 percent) had a defect in the image obtained at rest. The magnitude of myocardial image defects was typically great; some patients had an image abnormality without other clinical evidence (angina, S-T depression) of ischemia. The mean ejection fraction, assessed in 16 patients with radionuclide angiography, was 0.41 +/- 0.15 (standard deviation); in 5 of the 16 ejection fraction was normal (more than 0.50) and in 3 it was severely abnormal (less than 0.25). Thus, noninvasive radionuclide studies defined a broad spectrum of ischemic and ventriculographic abnormalities in survivors of sudden cardiac death. Further application of these noninvasive studies may identify those at high risk.


A simple and inexpensive method to control oxygen concentrations within physiological and neoplastic ranges.
Traditional methods for regulating oxygen concentration ([O2]) in in vitro experiments over the range found in normal and tumor tissues require the use of expensive equipment to generate controlled gas atmospheres or the purchase of a range of gas cylinders with certified O2 percentages. Here we describe a simple and inexpensive enzymatic method for generating low, precise steady-state [O2] levels that are stable for several hours. This method is particularly applicable to the in vitro study of some classes of hypoxia-targeted antitumor prodrugs and bioreductively activated agents.


Mesenchymal Stromal Cell Bioreactor for Ex Vivo Reprogramming of Human Immune Cells.
Bone marrow mesenchymal stromal cells (MSCs) have been studied for decades as potent immunomodulators. Clinically, they have shown some promise but with limited success. Here, we report the ability of a scalable hollow fiber bioreactor to effectively maintain ideal MSC function as a single population while also being able to impart an immunoregulatory effect when cultured in tandem with an inflamed lymphocyte population. MSCs were seeded on the extraluminal side of hollow fibers within a bioreactor where they indirectly interact with immune cells flowing within the lumen of the fibers. MSCs showed a stable and predictable metabolite and secreted factor profile during several days of perfusion culture. Exposure of bioreactor-seeded MSCs to inflammatory stimuli reproducibly switched MSC secreted factor profiles and altered microvesicle composition. Furthermore, circulating, activated human peripheral blood mononuclear cells (PBMCs) were suppressed by MSC bioreactor culture confirmed by a durable change in their immunophenotype and function. This platform was useful to study a model of immobilized MSCs and circulating immune cells and showed that monocytes play an important role in MSC driven immunomodulation. This coculture technology can have broad implications for use in studying MSC-immune interactions under flow conditions as well as in the generation of ex vivo derived immune cellular therapeutics.


Expanding the repertoire of amyloid polymorphs by co-polymerization of related protein precursors.
Amyloid fibrils can be generated from proteins with diverse sequences and folds. Although amyloid fibrils assembled in vitro commonly involve a single protein precursor, fibrils formed in vivo can contain more than one protein sequence. How fibril structure and stability differ in fibrils composed of single proteins (homopolymeric fibrils) from those generated by co-polymerization of more than one protein sequence (heteropolymeric fibrils) is poorly understood. Here we compare the structure and stability of homo and heteropolymeric fibrils formed from human β2-microglobulin and its truncated variant ΔN6. We use an array of approaches (limited proteolysis, magic angle spinning NMR, Fourier transform infrared spectroscopy, and fluorescence) combined with measurements of thermodynamic stability to characterize the different fibril types. The results reveal fibrils with different structural properties, different side-chain packing, and strikingly different stabilities. These findings demonstrate how co-polymerization of related precursor sequences can expand the repertoire of structural and thermodynamic polymorphism in amyloid fibrils to an extent that is greater than that obtained by polymerization of a single precursor alone.


DNA interaction and efficient antimicrobial activities of 4N chelating metal complexes.
A new series of metal(II) complexes using a symmetric Schiff base ligand, obtained by the condensation reaction of 4-formyl-N,N-dimethylaniline with benzene-1,2-diamine were synthesized and characterized. The various physico-chemical data indicate that the complexes have octahedral geometry. The intrinsic binding constant of the complexes with DNA is explored. The UV-Vis., circular dichorism, fluorescence emission spectral data and the viscosity measurements indicate that the complexes bind to calf thymus DNA (CT DNA) by intercalative mode. The intrinsic binding constants of Cu(II), Ni(II), Co(II) and Zn(II) complexes are found to be 7.1×10(4), 5.2×10(4), 1.8×10(5) and 6.3×10(4) M(-1), respectively. The cleavage studies of these complexes are investigated by gel electrophoresis method in the presence of peroxide. The complexes exhibit enhanced biological activities compared to the free ligand.


Differentiating among incretin-based therapies in the management of patients with type 2 diabetes mellitus.
The glucagon-like peptide-1 receptor (GLP-1R) agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors have become important options for the management of patients with type 2 diabetes mellitus. While the GLP-1R agonists and DPP-4 inhibitors act on the incretin system to regulate glucose homeostasis, there are important clinical differences among the five agents currently available in the U.S. For example, the GLP-1R agonists require subcutaneous administration, produce pharmacological levels of GLP-1 activity, promote weight loss, have a more robust glucose-lowering effect, and have a higher incidence of adverse gastrointestinal effects. In contrast, the DPP-4 inhibitors are taken orally, increase the half-life of endogenous GLP-1, are weight neutral, and are more commonly associated with nasopharyngitis. Differences in efficacy, safety, tolerability, and cost among the incretin-based therapies are important to consider in the primary care management of patients with type 2 diabetes mellitus.


Chronic post-traumatic headache associated with minor cranial trauma: a description of cephalalgic patterns.
We studied a group of 93 patients who had not previously suffered headache and who were consecutively admitted to the Emergency Department of the hospitals of Novara and Borgomanero, Italy because of a cranial trauma definable as minor according to the current International Headache Society (IHS) criteria. Two weeks after admission, all patients underwent a semi-structured interview which revealed that 24 (25.8%) had headache; 21 of these (22.5% of the original 93 patients) also had headache when they underwent a second interview eight weeks after the traumatic event. These 21 patients were diagnosed as having chronic post-traumatic headache associated with minor cranial trauma (5.2.2 of the IHS classification), and the prevalent clinical pattern of headache presentation was examined with the aim of attributing the fourth IHS classification code number. Eighteen of the 21 patients were found to have a tension-type pattern (126.96.36.199), and the remaining three had migraine (18.104.22.168); none had cluster headache (184.108.40.206). These data demonstrate a large prevalence of tension-type headache in patients with class 5.2.2 post-traumatic headache, and confirm the results of previously published studies that were not based on the diagnostic criteria of the current classification.


The outcome of living donor liver transplant recipients with recent episodes of spontaneous bacterial peritonitis.
spontaneous bacterial peritonitis (SBP) is a common complication in patients with cirrhosis and is associated with a high mortality rate. Only a few reports have analyzed the impact of treated SBP that occurs in the immediate pre-operative period on outcome after a living donor liver transplantation (LDLT). The results of whether post-transplant patients are dependent on pre-transplant infections are still debatable and unclear. Therefore, this study examined the outcomes of LDLT recipients with recent episodes of SBP and LDLT recipients without prior episodes of SBP. the records of 62 LDLT recipients who underwent LDLT were retrospectively reviewed. Twenty-four (36 %) recipients had at least one episode of SBP before LDLT. However, active SBP was not present in any of the recipients at the time of LDLT. Both recipient groups were compared in terms of demographic profile, perioperative and postoperative variables and outcomes. higher pre-operative Child-Turcotte-Pugh (CTP) score (mean [SD] 11.77 [1.37] vs 10.5 [1.22], p < 0.001) and prior history of renal dysfunction (mean serum creatinine [SD] 1.715 [1.08] vs 1.02 [0.479] mg/dl, p = 0.002) were more commonly associated with the SBP group as compared to the non-SBP group. However, there was no statistically significant difference between the two groups in terms of the following variables: previous diabetes mellitus (3 [12.5 %] vs 6 [15.8 %]), pre-operative model for end-stage liver disease (MELD) score (median [IQR] 21 [10-37] vs 22 [9-39]), operative time (mean [SD] 789.57 [153.49] vs 800.86 [138.69] min), total number of blood transfusion (median [IQR] 10 [2-19] vs 8 [1-18]), hospital stay (median 21 vs 20 days), re-exploration (4 [16.6 %] vs 2 [5.3 %]), postoperative sepsis (8 [33 %] vs 5 [13 %]) and 30-day mortality (3 [12.5 %] vs 2 [5.3 %]). the presence of previous episodes of pre-operative SBP in LDLT recipients does not result in adverse post-operative short-term outcomes.


Magnetic resonance imaging of rheumatoid meningitis: a case report and literature review.
Rheumatoid meningitis is a rare and serious complication of rheumatoid arthritis (RA) with high mortality rate. Clinical importance of the disease is high because diagnosis is difficult, and the disease is treatable if diagnosed successfully. We present the clinical and cranial magnetic resonance imaging findings of 62-year-old female patient with RA who has been followed up for 4 years.


Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio is linked to advanced non-alcoholic fatty liver disease lean patients.
A small but significant proportion of patients with normal body mass index show non-alcoholic fatty liver disease (NAFLD). Oxidized low-density lipoprotein (LDL) is a powerful immunogenic molecule, which causes oxidative stress and produces antibodies (oxLDL-ab). We aimed to analyze the role of oxLDL-ab on histological features in lean-NAFLD patients. Seventy-two biopsy-proven NAFLD patients were included. Lean patients showed body index mass of <30 kg/m(2) . Liver biopsies were assessed by one pathologist blinded to clinical data. Histological features were non-alcoholic steatohepatitis (NASH), steatosis, hepatocellular ballooning, and liver fibrosis. Metabolic and hepatic profiles were analyzed, and lipid-lowering medication was recorded. OxLDL-ab levels were measured by ELISA. OxLDL-ab-based lipid indexes analyzed: oxLDL-ab/total cholesterol ratio; oxLDL-ab/LDL-c ratio; oxLDL-ab/high-density lipoprotein cholesterol (HDL-c) ratio; and oxLDL-ab/oxLDL ratio. Lean-NAFLD patients presented 26.5% (9/34) of NASH. OxLDL-ab/HDL-c ratio (r = 0.570; n = 34; P = 0.001) correlated with NAS score and was the only variable associated with NASH in the multivariate analysis [odds ratio, OR, 1.10 (95% confidence interval, CI: 1.01-1.21); P = 0.039]. Severe steatosis was present in 41.2% (14/34) of lean-NAFLD patients. OxLDL-ab/HDL-c ratio was higher in patients with grade-III steatosis (54.9 (37.3-124.6)) than those with grade II (37.1 (20.2-71.1)) and grade I (17.7 (13.1-22.8)) (P = 0.018). Hepatocellular ballooning was present in 20.6% (7/34) of lean-NAFLD patients, and OxLDL-ab/HDL-c ratio (OR 1.03 [95% CI: 1.01-1.05]; P = 0.050) was independently associated with histological features. OxLDL-ab/HDL-c ratio was higher in patients with advanced fibrosis (39.8 (22.9-121.6) vs 17.7 (13.9-30.9); P = 0.025), increasing gradually with the fibrosis stage (P = 0.042) and remained in the final multivariate model [OR 1.05 (95% CI: 1.00-1.11); P = 0.05]. However, in obese-NAFLD patients, oxLDL/HDL-c ratio was not associated with histological features. Oxidized low-density lipoprotein antibodies/high-density lipoprotein cholesterol ratio could represent an interesting biomarker associated with NASH, hepatocellular ballooning, and liver fibrosis, in lean patients. OxLDL-ab/HDL-c could play an important role for distinguishing patients with and without NAFLD complications.


Synthesis of adenosine triphosphate by an artificially imposed electrochemical proton gradient in bovine heart submitochondrial particles.
Submitochondrial particles subjected to an artificially imposed electrochemical proton gradient consisting of a pH gradient (acid to base transition) and membrane potential (low to high K-+ transition in the presence of valinomycin) catalyzed the net synthesis of 2.5 nmol of [-32P]ATP per mg of protein from ADP and 32-Pi. Optimal reaction conditions included incubation of submitochondrial particles in malonate at pH 5.0 with valinomycin in the absence of added K-+, followed by a rapid transition to pH 7.5 and 100 mM K-+. ATP synthesis continued for about 6 s and was sensitive to uncouplers or oligomycin but insensitive to inhibitors of electron transport. Lower amounts of ATP were formed by either the pH gradient (25%) of K-+ gradient (15%) alone. These results demonstrate that an electrochemical gradient of protons can drive the synthesis of ATP by reversal of the proton-translocating ATPase independent of electron transport.


A resonance Raman study on the interaction of rifampicin with Escherichia coli RNA polymerase.
The technique of resonance Raman spectroscopy has been used to investigate the interaction of the antibiotic rifampicin with Escherichia coli RNA polymerase. Spectra were analyzed by generating the first derivative of each recorded spectrum using the Savitsky-Golay algorithm. The only band that shifted significantly in the resonance Raman spectrum of rifampicin upon the formation of the drug-core polymerase complex was the amide III band. It underwent an 8 cm-1 shift from 1306 cm-1 in aqueous solution to 1314 cm-1. A comparable shift was observed for the rifampicin-holoenzyme complex. Thus, the interaction of the sigma subunit with the core polymerase does not significantly alter the manner in which rifampicin interacts with RNA polymerase. The nature of this shift has been analyzed further by recording the resonance Raman spectrum of rifampicin in a variety of solvents with different hydrogen-bonding solvents (benzene and carbon disulfide) the amide III band was observed at approximately 1220 cm-1; in dimethyl sulfoxide, a weak hydrogen-bond acceptor, 1274 cm-1; in water, a strong hydrogen-bonding solvent, 1306 cm-1; and finally, in triethylamine, a stronger hydrogen-bonding solvent than water, it was observed at 1314 cm-1. Thus, as the hydrogen-bonding ability of the solvent increased, the amide III band shifted to higher frequency. Based on these results, the rifampicin binding site in RNA polymerase provides a stronger hydrogen-bonding environment for the amidic proton of rifampicin than is encountered when rifampicin is free in aqueous solution.


Validation of lung cancer polygenic risk scores in a high-risk case-control cohort.
Screening with low-dose computed tomography reduces lung cancer (LC) mortality. Risk prediction models used for screening selection do not include genetic variables. Here, we investigated the performance of previously published polygenic risk scores (PRSs) for LC, considering their potential to improve screening selection. We validated 9 PRSs in a high-risk case-control cohort, comprising genotype data from 652 surgical patients with LC and 550 cancer-free, high-risk (PLCOM2012 score ≥ 1.51%) participants of the Manchester Lung Health Check, a community-based LC screening program (n = 550). Discrimination (area under the curve [AUC]) between cases and controls was assessed for each PRS independently and alongside clinical risk factors. Median age was 67 years, 53% were female, 46% were current smokers, and 76% were National Lung Screening Trial eligible. Median PLCOM2012 score among controls was 3.4%, 80% of cases were early stage. All PRSs significantly improved discrimination, AUC increased between +0.002 (P = .02) and +0.015 (P < .0001), compared with clinical risk factors alone. The best-performing PRS had an independent AUC of 0.59. Two novel loci, in the DAPK1 and MAGI2 genes, were significantly associated with LC risk. PRSs may improve LC risk prediction and screening selection. Further research, particularly examining clinical utility and cost-effectiveness, is required.


Prolonged strenuous exercise alters the cardiovascular response to dobutamine stimulation in male athletes.
Prolonged strenuous exercise has been associated with transient impairment in left ventricular (LV) systolic and diastolic function that has been termed 'cardiac fatigue'. It has been postulated that cardiac beta-adrenoreceptor desensitization may play a central role; however, data are limited. Accordingly, we assessed the cardiovascular response to progressive dobutamine stimulation after prolonged strenuous exercise (2 km swim, 90 km bike, 21 km run). Nine experienced male athletes were studied: PRE (2-3 days before), POST (after) and REC (1-2 days later). The cardiovascular response to progressive continuous dobutamine stimulation (0, 5, 20, and 40 microg kg(-1) min(-1)) was assessed, including heart rate (HR), systolic blood pressure (SBP), LV cavity areas (two-dimensional echocardiography) and contractility (end-systolic elastance, SBP/end-systolic cavity area (ESCA)). POST there was limited evidence of myocardial necrosis (measured by troponin I), while catecholamines were elevated. HR was higher POST (mean +/-s.d.; PRE, 58 +/- 9; POST, 79 +/- 9; REC, 57 +/- 7 beats min(-1); P < 0.05), while SBP was lower (PRE, 127 +/- 15; POST, 116 +/- 9; REC, 121 +/- 12 mmHg; P < 0.05). A blunted HR, SBP and LV contractility (SBP/ESCA; PRE 29 +/- 6 versus POST 20 +/- 6 mmHg cm(-2); P < 0.05) response to dobutamine was demonstrated POST, with values returning towards baseline in REC. Following prolonged strenuous exercise, the chronotropic and inotropic response to dobutamine stimulation is blunted. This study supports the hypothesis that beta-receptor downregulation and/or desensitization may play a major role in prolonged-strenuous-exercise-mediated cardiac fatigue.


The Evolving Family Mealtime: Findings From Focus Group Interviews With Hispanic Mothers.
Given the protective effects of shared family mealtimes and the importance of family in the Hispanic culture, this context should be explored further to determine how it can be leveraged and optimized for interventions. This study aimed to explore contextual factors associated with family mealtimes in Mexican and Puerto Rican families. A total of 63 mothers participated in 13 focus group interviews across 4 states. Thematic analysis was used to analyze transcripts. Seven overarching themes were identified through the thematic analysis. Themes reflected who was present at the mealtime, what occurs during mealtime, the presence of television, the influence of technology during mealtime, and how mealtimes have changed since the mothers were children. Hispanic mothers may be adapting family mealtimes to fit their current situations and needs, keeping the television and other devices on during mealtimes, and making additional meals for multiple family members to appease everyone's tastes. All of these are areas that can be incorporated into existing culturally tailored obesity prevention programs to help families lead healthier lives.


Mucoepidermoid carcinoma of the esophagus: a case report.
The eighth reported case of mucoepidermoid carcinoma of the esophagus is described by light microscopic and ultrastructural examination. The reason of such a paucity of reports, the probable origin, and the natural history of this neoplasm are examined through our observations and reference to the literature.


The cytolytic effect of L-2,4 diaminobutyric acid with malignant glioma cells and fibroblasts.
L-2,4-Diaminobutyric acid (DABA), an amino acid analogue, produced a cytolytic effect with a human glioma cell line, SKMG-1, and normal human fibroblasts. The concentrations of DABA necessary to reduce the cell count to 50% of control (LD50) following a 24-h incubation at 37 degrees C were 12.5 mM for the human fibroblasts and 20 mM for the glioma cell line. The concentrations of DABA necessary to produce an LD50 after a 48-h incubation at 37 degrees C were 10 mM for the human fibroblasts and 14 mM for the human glioma cell line. The cytolytic effect of DABA was similar in the absence or the presence of serum with the human glioma cell line. The cytolytic effect of 20 mM DABA was partially prevented by the presence of 5 mM methyl-AIB. DABA was not preferentially toxic to this human glioma cell line compared with normal fibroblasts.


The activated ATM/p53 pathway promotes autophagy in response to oxidative stress-mediated DNA damage induced by Microcystin-LR in male germ cells.
Microcystin-LR (MC-LR) is an intracellular toxin with multi-organ toxicity and the testis is one of its important target organs. Although there is increasing research on MC-LR in male reproductive toxicity, the association between DNA damage and autophagy induced by MC-LR in male germ cells are still unclear. Therefore, it is important to explore the mechanism of MC-LR-induced DNA damage and the role of the activated ATM/p53 signaling pathway in testicular toxicity. The present study showed that MC-LR exposure significantly reduced gonadal index and induced pathological damage of the testes in mice. In addition, MC-LR increased the oxidative stress-related indicator hydroxyl radical, accompanied by increased levels of DNA damage-related indicators gamma-H2AX, 8-hydroxy-2'-deoxyguanosine, the olive tail moment (OTM) and DNA content of comet tail (TailDNA%) in trailing cells. Moreover, MC-LR activated the ATM/p53 pathway by enhancing the phosphorylation levels of ATM, CHK2 and p53 proteins, and then led to cell autophagy, ultimately triggering disrupted testicular cell arrangement, reduced sperm count and spermatogenic cell shedding. Importantly, after pretreatment with the antioxidant NAC, the expression levels of DNA damage-related indicators and the extent of damage in male germ cells were significantly reduced. Furthermore, pretreatment with the ATM inhibitor KU55933 could reduce the occurrence of autophagy and mitigate testicular toxicity of MC-LR through inhibiting the activation of the ATM/p53 pathway. These results indicate that MC-LR-induced oxidative stress can activate the DNA damage-mediated ATM/p53 signalling pathway to induce autophagy in male germ cells. This study provides a novel insight to further clarify the reproductive toxicity caused by MC-LR and to protect male reproductive health.


High-density genetic and physical mapping of DNA markers near the X-linked Alport syndrome locus: definition and use of flanking polymorphic markers.
To refine the genetic and physical mapping of the locus for Alport syndrome (ATS), 22 X-chromosome restriction fragment length polymorphism (RFLP) markers that fall between Xq21.3 and Xq25 were tested for genetic linkage with the disease and also mapped with respect to a series of physical breakpoints in this region. The location of the COL4A5 gene, which has recently been shown to be mutated in at least some families with Alport syndrome, was determined with respect to the same physical breakpoints. Two large Utah kindreds were included in the genetic studies, kindreds P and C, with 125 and 63 potentially informative meioses, respectively. Both kindreds have essentially identical nephritis; however, kindred P has sensorineural hearing loss associated with the nephritis, while kindred C does not. A mutation in COL4A5 has been demonstrated for kindred P, but no change in this gene has yet been detected for kindred C. Twelve informative probes did not recombine with the disease locus in either kindred (theta = 0.0, with combined lod scores for the two kindreds ranging from 7.7 to 30.0). The closest markers that could be demonstrated to flank the disease locus were the same for each kindred and thus the locations of the mutations causing the two disease phenotypes are not distinguishable at the current level of genetic resolution. The flanking markers are also useful for the resolution of questionable diagnoses and allow accurate estimates for these families of the rate of sporadic hematuria in noncarrier females (7%) and the penetrance of hematuria for carrier females (93%).


Characterization of supported cylinder-planar germanium waveguide sensors with synchrotron infrared radiation.
Cylinder-planar Ge waveguides are being developed as evanescent-wave sensors for chemical microanalysis. The only non-planar surface is a cylinder section having a 300-mm radius of curvature. This confers a symmetric taper, allowing for direct coupling into and out of the waveguide's 1-mm(2) end faces while obtaining multiple reflections at the central <30-microm-thick sensing region. Ray-optic calculations indicate that the propagation angle at the central minimum has a strong nonlinear dependence on both angle and vertical position of the input ray. This results in rather inefficient coupling of input light into the off-axis modes that are most useful for evanescent-wave absorption spectroscopy. Mode-specific performance of the cylinder-planar waveguides has also been investigated experimentally. As compared to a blackbody source, the much greater brightness of synchrotron-generated infrared (IR) radiation allows a similar total energy throughput, but restricted to a smaller fraction of the allowed waveguide modes. However, such angle-selective excitation results in a strong oscillatory interference pattern in the transmission spectra. These spectral oscillations are the principal technical limitation on using synchrotron radiation to measure evanescent-wave absorption spectra with the thin waveguides.


The MRE11 opposes white spot syndrome virus infection through the IRF and Dorsal mediated antiviral pathways in shrimp.
Meiotic recombination 11 (MRE11), a key component of the MRE11-RAD50-NBS1 (MRN) complex, plays important roles in damaged DNA repair and immune response. In this study, we described the molecular cloning of a new member of MRE11 from Litopenaeus vannamei named as LvMRE11. The full length of LvMRE11 was 2999 bp, including a 1947 bp open reading frame (ORF) that encoded a putative protein of 648 amino acids with a calculated molecular weight of ∼73.2 kDa LvMRE11 was universally expressed in all tested tissues and its expression in intestine was responsive to the challenge of white spot syndrome virus (WSSV), poly (I: C), poly [dA:dT], CpG-ODN 2006 and IFN stimulatory DNA (ISD). The dsRNA-mediated knockdown of LvMRE11 enhanced the susceptibility of shrimps to WSSV infection, as manifested by a higher mortality and viral loads observed in LvMRE11 silenced shrimps. Besides, silencing of LvMRE11 resulted in decreased expression levels of IRF-Vago-JAK/STAT pathway components, and Dorsal but not the Relish, as well as several antimicrobial peptides (AMPs). In conclusion, we provided some evidences that the involvement of LvMRE11 in innate immune against virus infection probably through regulating the IRF and Dorsal mediated antiviral pathways.


Phytochemical profiling of Piper crocatum and its antifungal activity as Lanosterol 14 alpha demethylase CYP51 inhibitor: a review.
Mycoses or fungal infections are a general health problem that often occurs in healthy and immunocompromised people in the community. The development of resistant strains in Fungi and the incidence of azole antibiotic resistance in the Asia Pacific which reached 83% become a critical problem nowadays. To control fungal infections, substances and extracts isolated from natural resources, especially in the form of plants as the main sources of drug molecules today, are needed. Especially from Piperaceae, which have long been used in India, China, and Korea to treat human ailments in traditional medicine. The purpose of this review was to describe antifungal activity from Piper crocatum and its phytochemical profiling against lanosterol 14 alpha demethylase CYP51. The methods used search databases from Google Scholar to find the appropriate databases using Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) flow diagram as a clinical information retrieval method. From 1,150,000 results search by database, there were 73 selected articles to review. The review shows that P. crocatum contains flavonoids, tannins, terpenes, saponins, polyphenols, eugenol, alkaloids, quinones, chavibetol acetate, glycosides, triterpenoids or steroids, hydroxychavikol, phenolics, glucosides, isoprenoids, and non-protein amino acids. Its antifungal mechanisms in fungal cells occur due to ergosterol especially lanosterol 14 alpha demethylase CYP51 inhibition as a result of 5,6 desaturase (ERG3) downregulation. P. crocatum has an antifungal activity by its phytochemical profiling that act against fungi by inhibiting the fungal cytochrome P 450 pathway, make damaging cell membranes, fungal growth inhibition, morphological changes, and fungal cell lysis.


[Oxytocin in schizophrenia : Evidence for an etiological and therapeutic relevance of the social neuromodulator].
Neurobiological results from animal models as well as biochemical and genetic findings in patients indicate that the oxytocin (OT) system may be dysfunctional in schizophrenia. On this pathogenetic basis transnasally administered OT (tnOT) could be an innovative treatment option for schizophrenia. Experimental data from animal studies are also suggestive of a particular effectiveness in treatment-resistant schizophrenia. To date, clinical data on tnOT treatment of schizophrenia patients does not unequivocally support a general therapeutic effect on the psychopathology but suggests positive effects on higher integrated social cognitive performance, such as empathy and mentalization. In particular, tnOT augmentation of a social cognitive skills training resulted in a marked and lasting treatment effect; however, numerous person- and context-dependent variables can potentially moderate individual effects of OT and may even reverse effects in certain constellations. Most clinical studies so far have not systematically accounted and controlled for these factors with the probable result of larger variance of recorded treatment effects and lower likelihood of ascertaining positive effectiveness. Furthermore, there is still a gap of knowledge on dose response relations and central nervous system (CNS) permeation in man following tnOT administration. This review aims to give a concise overview on the evidence for the etiological relevance of the neurohormone OT and its treatment potential in schizophrenia.


Principal components analysis for source localization of VEPs in man.
This study defines and compares the topologies of the visual evoked potentials to various stimuli such as pattern onset/offset, pattern reversal, pattern motion and high frequency luminance flicker. The responses recorded from 24 occipital derivations were examined using a three sphere conductance model to represent the head, with the assumption that activity from an underlying cortical source is equivalent to a single dipole. Principal components analysis was used to find the dimensionality of the data space. From this analysis could be concluded that all stimuli evoked responses in the primary visual cortex. Only pattern onset, and to a lesser degree pattern offset and pattern reversal, yielded activity in higher visual areas. In particular it has been shown that the CI, CII interval of the pattern onset response has its origins in two different cortical regions. A fast positive (CI)-negative (part of the CII) component arises from area 18 (or 19), a slower negative (initial part of CII) component comes from area 17.


Cytotoxic agents from Bursera klugii (Burseraceae) I: isolation of sapelins A and B.
A crude chloroform-soluble fraction of the ethanol extract of the leaves of Bursera klugii showed activity against two test systems, the P-388 lymphocytic leukemia (3PS) and the human epidermoid carcinoma of the nasopharynx (9KB). The PS activity was due to two constituents, sapelins A and B.


Experimental comparative study of surgical and needle biopsies of the testis.
Testis biopsy was performed on 78 rats in order to compare needle and surgical biopsies. The rats were autopsied 7, 15, 30, 60, and 90 days after biopsy. Both techniques provided tissue of equally good quality for histopathological examination and led to irreversible hypospermatogenesis of the biopsied and the contralateral testes.


Phylogeography of a widely distributed plant species reveals cryptic genetic lineages with parallel phenotypic responses to warming and drought conditions.
To predict how widely distributed species will perform under future climate change, it is crucial to understand and reveal their underlying phylogenetics. However, detailed information about plant adaptation and its genetic basis and history remains scarce and especially widely distributed species receive little attention despite their putatively high adaptability. To examine the adaptation potential of a widely distributed species, we sampled the model plant Silene vulgaris across Europe. In a greenhouse experiment, we exposed the offspring of these populations to a climate change scenario for central Europe and revealed the population structure through whole-genome sequencing. Plants were grown under two temperatures (18°C and 21°C) and three precipitation regimes (65, 75, and 90 mm) to measure their response in biomass and fecundity-related traits. To reveal the population genetic structure, ddRAD sequencing was employed for a whole-genome approach. We found three major genetic clusters in S. vulgaris from Europe: one cluster comprising Southern European populations, one cluster of Western European populations, and another cluster containing central European populations. Population genetic diversity decreased with increasing latitude, and a Mantel test revealed significant correlations between F ST and geographic distances as well as between genetic and environmental distances. Our trait analysis showed that the genetic clusters significantly differed in biomass-related traits and in the days to flowering. However, half of the traits showed parallel response patterns to the experimental climate change scenario. Due to the differentiated but parallel response patterns, we assume that phenotypic plasticity plays an important role for the adaptation of the widely distributed species S. vulgaris and its intraspecific genetic lineages.


Cross-linked matrix tissue sealant protects against mortality and hemorrhage in an acute renal injury model in heparinized rats.
We evaluated the efficacy of a cross-linked matrix tissue sealant compared with oxidized cellulose and electrocautery in an acute renal injury model. Sprague-Dawley rats underwent partial nephrectomy after intravenous heparin anticoagulation. The cut surface received 1 of 4 therapies, namely no treatment, cross-linked matrix tissue sealant, electrocautery or Surgicel (Johnson & Johnson, New Brunswick, New Jersey) oxidized cellulose. Blood pressure was continually monitored, survival time was determined and total blood loss was quantified in each animal. Animals that received no treatment, electrocautery or oxidized cellulose died within 13 minutes of injury with a decline in blood pressure to 0 mm. Hg. In cross-linked matrix treated rats hemostasis was immediate, resulting in no blood loss after cross-linked matrix application. Mean arterial pressure +/- SEM was maintained at 136 +/- 6 mm. Hg. All cross-linked matrix treated animals survived. Cross-linked matrix tissue sealant provided immediate hemostasis and protection from a decline in blood pressure after renal trauma in heparinized rats. Cross-linked matrix tissue sealant may benefit patients with severe renal injuries. In the future cross-linked matrix may be useful for long-term partial nephrectomy repair.


Breast Lymphedema After Conservative Breast Surgery: An Up-to-date Systematic Review.
Although arm lymphedema following breast cancer treatment is a common complication; breast lymphedema following treatment is not uncommon. Several risk factors were found to contribute to breast lymphedema, including axillary surgery, high body mass index (BMI), increased bra cup size, adjuvant chemotherapy, locoregional and radiotherapy boost, and upper outer quadrant tumors. We aimed to provide a review to help avoiding or management of breast lymphedema. The search term 'breast lymphedema' was combined with 'breast conservative surgery' and was used to conduct a literature research in PubMed and Medline. The term lymphedema was combined with breast, conservative, and surgery to search the Embase database. All papers published in English were included with no exclusion date limits. A total of 2155 female patients were included in this review; age ranged from 26 to 90 years. The mean BMI was 28.4 of the studies that included patients who underwent conservative breast surgery. Incidence of breast lymphedema ranged from 24.8% to 90.4%. Several risk factors were linked to breast lymphedema after conservative breast surgery, such as BMI, breast size, tumor size, tumor site, type of surgery, and adjuvant therapy. Treatment options focused on decongestive lymphatic therapy, including manual lymphatic drainage, self-massaging, compression bras, or Kinesio taping. Breast lymphedema is a relatively common complication, yet there is no clear consensus on the definition or treatment options.


Temperal and spatial expression of CCN1, CCN3, CCN4, CCN5 and CCN6 proteins in the developing postnatal teeth.
CCN proteins are matricellular proteins and are important modulators of development and function of adult organs. However, there is no literature reporting the localization of CCN proteins during postnatal tooth development and the formation of periodontium. Therefore, the aim of our study was to investigate the expression of CCN1, CCN3, CCN4, CCN5 and CCN6 in the developing postnatal teeth. Wistar rats were used at postnatal (PN) 3.5, 7, 16 and 21 days and maxillas were processed for immunohistochemistry. At PN3.5 and PN7, preameloblasts (PA), secretory ameloblasts (SA), odontoblasts (OD) and dental pulp (DP) showed moderate to strong staining for CCN1, CCN4 and CCN6 respectively. CCN5 was intensely expressed in predentin, whereas CCN5 was undetectable in PA, SA, OD and DP. At PN16 and PN21, moderate to strong reaction with CCN1, CCN4 and CCN6 was evident in OD, DP, reduced enamel epithelium (REE), osteoblasts (OB) and periodontal ligament (PDL) respectively, while CCN5 was negative to weakly expressed in REE, OD, DP, OB, PDL and osteocytes (OC). Interestingly, the expression of CCN1, CCN4 and CCN6 was initially negative at PN16 but strong at PN21 in OC. Furthermore, there was no staining for CCN3 in the tissues studied. These results demonstrated that the expression pattern of CCN1, CCN4 and CCN6 is similar and inversely correlated with that of CCN3. CCN5 exhibits a unique distribution pattern. These data indicate that CCN proteins might play regulatory roles in amelogenesis, dentinogenesis, osteogenesis and PDL homeostasis.


Effects of sugar additives on protein stability of recombinant human serum albumin during lyophilization and storage.
Few researches on the protein stabilization of recombinant human serum albumin (rHSA) have been done. In the present study, we assessed the impact of sugar lyoprotectants on the protein stability of lyophilized rHSA (65 KDa) in the solid state. For the assessment, rHSA was formulated with sucrose and trehalose, respectively, alone or in combination with mannitol, which were lyophilized and stored at 35 degrees C. Degradation and aggregation of the resulting lyophilized formulations was analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE). Induction of amorphous state by the lyophilactants with rHSA was determined by differential scanning calorimetry (DSC). The protein secondary structure of the rHSA in the formulations was analyzed by Fourier transform infrared spectroscopy (FT-IR). Results from SDS-PAGE analysis displayed that mannitol formulation caused aggregation resulting in a few bands that were greater than 65 KDa, whereas sucrose and trehalose formulations revealed no such aggregation. However, the aggregation of the protein decreased when mannitol was combined with sucrose or trehalose. DSC measurement supported the electrophoresis data showing that sucrose and trehalose formed complete amorphous state, but mannitol induced a partial amorphous state. These data indicate during lyophilization the most effective protein protection against aggregation was provided by sucrose and trehalose. The protection lasted during 4 months storage at 35 degrees C. FT-IR analysis displayed that the sucrose formulation inhibited deamidation. In conclusion, our data suggest that sucrose and trehalose as additives seems to be sufficient to protect from lyophilization of rHSA protein and also maintain its stability in the solid state during storage.


Stromal cell-derived factor-1 (SDF-1) enhances cells invasion by αvβ6 integrin-mediated signaling in ovarian cancer.
Ovarian carcinoma is a common gynecological malignancy and a great threat to health as a result of metastasis. The chemokine stromal-derived factor (SDF-1) plays multiple roles in tumor pathogenesis. However, the precise molecular mechanism underlying SDF-1-induced ovarian cancer cell invasion is still undefined. αvβ6 integrin is an important factor in tumor progression. Therefore, we speculate that SDF-1-enhanced ovarian cancer cell invasion is related to αvβ6 integrin-mediated signaling. After culturing with SDF-1, an obvious time- and dose-dependent increase in αvβ6 integrin was demonstrated. Furthermore, CXC receptor 4 (CXCR4) was responsible for SDF-1-induced αvβ6 integrin expression. Simultaneously, SDF-1 was found to dramatically enhance extracellular matrix degradation via urokinase-type plasminogen activator (uPA) expression and cell invasion by αvβ6 integrin expression; these reinforce failed to be increased when pretreatment was performed with the CXCR4 inhibitor AMD3100 or anti-αvβ6 integrin antibody, respectively. In addition, αvβ6 integrin induced the phosphorylation of p38 MAPK and PI3 K/Akt, contributing to the up-regulation of uPA, as treatment with the specific inhibitor for p38 mitogen-activated protein kinases (MAPK) (SB203580) or phosphatidylinositol 3-kinase (PI3 K)/Akt (LY294002) strikingly abrogated uPA expression. Taken together, these results demonstrated that SDF-1 enhanced ovarian cancer cell invasion through αvβ6 integrin-mediated uPA expression via the p38 MAPK and PI3 K/Akt pathway. Consequently, our findings will provide a new explanation about how SDF-1 aggravates the pathogenesis of ovarian cancer.


Aberrant Upregulation of Compensatory Redox Molecular Machines May Contribute to Sperm Dysfunction in Infertile Men with Unilateral Varicocele: A Proteomic Insight.
Aims: To understand the molecular pathways involved in oxidative stress (OS)-mediated sperm dysfunction against a hypoxic and hyperthermic microenvironment backdrop of varicocele through a proteomic approach. Results: Protein selection (261) based on their role in redox homeostasis and/or oxidative/hyperthermic/hypoxic stress response from the sperm proteome data set of unilateral varicocele (UV) in comparison with fertile control displayed 85 to be differentially expressed. Upregulation of cellular oxidant detoxification and glutathione and reduced nicotinamide adenine dinucleotide (NADH) metabolism accompanied with downregulation of protein folding, energy metabolism, and heat stress responses were observed in the UV group. Ingenuity pathway analysis (IPA) predicted suppression of oxidative phosphorylation (OXPHOS) (validated by Western blotting [WB]) along with augmentation in OS and mitochondrial dysfunction in UV. The top affected networks indicated by IPA involved heat shock proteins (HSPs: HSPA2 and HSP90B1). Their expression profile was corroborated by immunocytochemistry and WB. Hypoxia-inducible factor 1A as an upstream regulator of HSPs was predicted by MetaCore. Occurrence of reductive stress in UV spermatozoa was corroborated by thiol redox status. Innovation: This is the first evidence of a novel pathway showing aberrant redox homeostasis against chronic hypoxic insult in varicocele leading to sperm dysfunction. Conclusions: Upregulation of antioxidant system and dysfunctional OXPHOS would have shifted the redox balance of biological redox couples (GSH/GSSG, NAD+/NADH, and NADP+/NADPH) to a more reducing state leading to reductive stress. Chronic reductive stress-induced OS may be involved in sperm dysfunction in infertile men with UV, where the role of HSPs cannot be ignored. Intervention with antioxidant therapy warrants proper prior investigation.


Limited photosynthetic plasticity in Sedum pulchellum Michx.
Carbon dioxide exchange pattern, carboxylating enzyme specific activity and titratable acidity were measureed for field collected individuals of Sedum pulchellum Michx., a winter annual of xeric cedar glade communities in central Tennessee. Evidence of a weak-CAM mode of photosynthesis was found on 4 of 27 sampling dates during a three year period. Three of these dates occurred during 1978, the driest study season, and nocturnal CO2 uptake contributed a maximum of 10% of the plants daily CO2 uptake. Weak CAM in the field was associated with elevated phosphoenol-pyruvate (PEP) carboxylase activity and, to a lesser degree, with decreased ribulose bisphosphate (RuBP) carboxylase activity. In contrast, carboxylating enzyme specific activities of the sympatric, obligate CAM species Opuntia compressa, a dominant perennial of the cedar glades, were highly stable.Weak CAM was also induced in S. pulchellum upon water stress in the laboratory. Again, weak CAM was associated with elevated PEP carboxylase and decreased RuBP carboxylase activities and represented a relatively minor CO2 uptake contribution. The potential ecological significance of this limited photosynthetic flexibility in S. puchellum is not obvious but it may play an important role in successful yearly reproduction in this annual species at a time when water stress is frequent.


Manual versus Mechanical Chest Compressions on Surfaces of Varying Softness with or without Backboards: A Randomized, Crossover Manikin Study.
Chest compression quality is decisive for overall outcome after cardiac arrest. Chest compression depth may decrease when cardiopulmonary resuscitation (CPR) is performed on a mattress, and the use of a backboard does not necessarily improve compression depth. Mechanical chest compression devices may overcome this problem. We sought to investigate the effectiveness of manual chest compressions both with and without a backboard compared to mechanical CPR performed on surfaces of different softness. Twenty-four advanced life support (ALS)-certified rescuers were enrolled. LUCAS2 (Physio-Control, Redmond, WA) delivers 52 ± 2 mm deep chest compressions and active decompressions back to the neutral position (frequency 102 min(-1); duty cycle, 50%). This simulated CPR scenario was performed on a Resusci-Anne manikin (Laerdal, Stavanger, Norway) that was lying on 3 different surfaces: 1) a concrete floor, 2) a firm standard mattress, and 3) a pressure-relieving mattress. Data were recorded by the Laerdal Skill Reporting System. Manual chest compression with or without a backboard were performed correctly less often than mechanical chest compressions (floor: 33% [interquartile range {IQR}, 27-48%] vs. 90% [IQR, 86-94%], p < 0.001; standard mattress: 32% [IQR, 20-45%] vs. 27% [IQR, 14-46%] vs. 91% [IQR, 51-94%], p < 0.001; and pressure-relieving mattress 29% [IQR, 17-49%] vs. 30% [IQR, 17-52%] vs. 91% [IQR, 87-95%], p < 0.001). The mean compression depth on both mattresses was deeper with mechanical chest compressions (floor: 53 mm [range, 47-57 mm] vs. 56 mm [range, 54-57 mm], p = 0.003; standard mattress: 50 mm [range, 44-55 mm] vs. 51 mm [range, 47-55 mm] vs. 55 mm [range, 54-58 mm], p < 0.001; and pressure-relieving mattress: 49 mm [range, 44-55 mm] vs. 50 mm [range, 44-53 mm] vs. 55 mm [range, 55-56 mm], p < 0.001). In this ∼6-min scenario, the mean hands-off time was ∼15 to 20 s shorter in the manual CPR scenarios. In this experimental study, only ∼30% of manual chest compressions were performed correctly compared to ∼90% of mechanical chest compressions, regardless of the underlying surface. Backboard use did not influence the mean compression depth during manual CPR. Chest compressions were deeper with mechanical CPR. The mean hands-off time was shorter with manual CPR.


Light and electron microscopic demonstration of phospholipase B activity in the mouse eosinophil.
Phospholipase B (EC 184.108.40.206) which hydrolyzes phospholipids in the alpha and beta positions was demonstrated in murine leukocytes using light and electron microscopic histochemical techniques. Leukocytes (neutrophils, lymphocytes, macrophages, eosinophils) were harvested from peritoneal exudates of mice. Cells were fixed in 4% calcium-formol fixative for 10 min at 4 degrees C for light microscopy and 30 min at room temperature for electron microscopy, after which they were incubated at 37 degrees C in medium at pH 6.6 containing 2 microM lysolecithin and CaCl2. The fatty acids released during the hydrolytic reaction were trapped as a calcium precipitate and were converted to a cobalt precipitate for light microscopy by treatment with cobalt acetate or to a lead precipitate for electron microscopy by treatment with lead nitrate. The reaction products were observed to be present in eosinophils and absent in neutrophils, lymphocytes and macrophages. It is concluded that the eosinophilic leukocyte is the carrier cell for phospholipase B in inflammatory reactions.


Plain Computed Tomography With Spectral Imaging Findings of Early Cerebral Ischemia.
To investigate the findings of plain spectral computed tomography (CT) with multiparameter of early cerebral ischemia. Thirty-three patients with suspected early cerebral ischemia who received a one-stop CT examination (plain scan with spectral CT imaging mode, CTP and CTA) of the brain were enrolled in this study. No clear lesion was observed in any patient on the plain CT. However, the CTA displayed evidence of vascular stenosis and the CTP displayed a corresponding low perfusion area consistent with early cerebral ischemia. Regions of interest were placed in the abnormal perfusion regions and the contralateral symmetric regions on plain CT. Then, the CT value of the monochromatic images (70 kV), the slope of the spectral HU curve, blood (iodine), iodine (water), and water (iodine) concentrations were measured. A paired t-test was performed for data comparison. The receiver operating characteristic curve was used to evaluate diagnostic performance. The CT values of the ischemic regions at 70 keV, the spectral HU curve, water, and blood values of the ischemic measurements were slightly lower than those of the contralateral symmetric regions (P < .05). Monochromatic images at 70 keV had the highest area under the curve value, and the sensitivity and specificity were 90.0% and 63.0%, respectively. The difference of monochromatic CT values, spectral HU curve, and basic material concentrations between the early cerebral ischemia region and the contralateral symmetric region on spectral CT imaging may provide a reference with the diagnosis of early cerebral ischemia.


Evaluation of the equine cardiovascular system.
A thorough examination of the cardiovascular system is an integral part of a physical examination in the horse. The normal equine cardiovascular parameters are discussed, with an emphasis on auscultatory findings. The availability and application of other diagnostic techniques are discussed based upon findings of the physical examination.


Production of pentaglycine-fused proteins using Escherichia coli expression system without in vitro peptidase treatment.
Conjugation of functional molecules to peptides is necessary for protein analysis and applications. Transpeptidase sortase A catalyzes the ligation reaction between the amino acid sequence LPXTG and polyglycine and allows for peptide sequence-specific molecular modifications. In this study, the preparation of pentaglycine-fused green fluorescent protein (G5-GFP) via methionine truncation mediated by Escherichia coli endogenous methionyl aminopeptidase was investigated. Some expression vectors of GFP presenting MetGly5 at the N-terminal were constructed, and N-terminal sequence analyses of the protein expressed in E. coli were performed. When the first codon of the GFP-encoding sequence was AUG, a mixture of GFP without pentaglycine and G5-GFP was obtained. In contrast, when the first codon AUG was replaced with a codon encoding alanine, G5-GFP was obtained uniformly. These results showed that the location of AUG in the expression vector had a significant influence on the preparation of polyglycine-fused proteins. The obtained findings are useful for the preparation of polyglycine-fused substrates using E. coli.


Optical monitoring of PO2 changes and simultaneous recording of bioelectric activity in human and animal brain slices.
For investigations of hypoxic effects in nervous tissue, brain slices are often used as a model system. This provides the advantage that parameters of the micromilieu, e.g. pH and temperature can easily be controlled and measurements of different data, e.g. bioelectric potentials, ion activities etc. can be performed. It is of special importance that the PO2 the slice preparation is exposed to is equally controlled under these conditions. Therefore, a PO2 monitoring system is needed which provides representative values for the tissue environment. This requirement is fulfilled by an optical PO2 sensing method based on phosphorescence quenching as a function of PO2. Here, the application of this method as adapted for use in in vitro models is described and compared to the polarographic oxygen-sensing method. Both the optical and polarographic methods are comparable regarding accuracy and response time of measurements. Furthermore, both the optical method and electrophysiological measurements can be combined. Lastly, under experimental conditions, neither the phosphorescent dye Palladium-meso-tetra-4-carboxyphenyl-porphine nor the illumination necessary for excitation of the dye influence bioelectric activity of neuronal tissue in vitro. In conclusion, the optical PO2 sensing method presented here provides a tool for reliable and continuous monitoring of PO2 in the immediate environment of brain slice preparations.


Osteogenesis imperfecta with congenital joint contractures (Bruck syndrome).
Five children from three unrelated families were born with symmetrical contractures of the knees, ankles and feet. An initial diagnosis of arthrogryposis multiplex was made, but frequent fracturing occurred after walking commenced and it was then recognised that the children had osteogenesis imperfecta. The pathogenesis of the congenital contractures is unknown, but the symmetry and lack of evidence of prior fracturing is suggestive of articular immobility during early intra-uterine development. The consistency of the anatomical distribution of the contractures, in the setting of a uniform OI phenotype, is suggestive of syndromic identity. A similar case was documented by Alfred Bruck in 1897 and we propose that the eponymous designation "Bruck syndrome" should be applied to the disorder.


Remediation of contaminated intertidal sediment by increasing permeability using active capping material.
A novel approach for the remediation of clayey sediment in intertidal zones was proposed, which entails increasing the soil permeability using an active capping agent. The agent, granulated coal ash (GCA), was developed using the granulation processes for coal fly ash. The GCA increased the permeability coefficient of the sediment by seven times, changing its the properties from a typical clayey silt to that of silt, according to the soil classification standards based on permeability coefficient. Increased permeability was attributed to Ca2+ ions, and adsorbed Na+ was immediately discharged, leading to a decrease in the sodium adsorption ratio. The activated flow of pore water stimulated nutrient loadings; PO4-P and NH4-N loads decreased by 55% and 44%, respectively. The GCA increased the dissolved oxygen by 1.8 mg/L and increased the redox potential in pore water from -370 to -306 mV vs. Ag/AgCl. According to the results presented in this study, active capping with GCA to increase soil permeability is a novel and promising technology for reducing the nutrient loads and increasing the oxidation of contaminated clayey sediment in intertidal zones.


Activation of G proteins by GIV-GEF is a pivot point for insulin resistance and sensitivity.
Insulin resistance (IR) is a metabolic disorder characterized by impaired insulin signaling and cellular glucose uptake. The current paradigm for insulin signaling centers upon the insulin receptor (InsR) and its substrate IRS1; the latter is believed to be the sole conduit for postreceptor signaling. Here we challenge that paradigm and show that GIV/Girdin, a guanidine exchange factor (GEF) for the trimeric G protein Gαi, is another major hierarchical conduit for the metabolic insulin response. By virtue of its ability to directly bind InsR, IRS1, and phosphoinositide 3-kinase, GIV serves as a key hub in the immediate postreceptor level, which coordinately enhances the metabolic insulin response and glucose uptake in myotubes via its GEF function. Site-directed mutagenesis or phosphoinhibition of GIV-GEF by the fatty acid/protein kinase C-theta pathway triggers IR. Insulin sensitizers reverse phosphoinhibition of GIV and reinstate insulin sensitivity. We also provide evidence for such reversible regulation of GIV-GEF in skeletal muscles from patients with IR. Thus GIV is an essential upstream component that couples InsR to G-protein signaling to enhance the metabolic insulin response, and impairment of such coupling triggers IR. We also provide evidence that GIV-GEF serves as therapeutic target for exogenous manipulation of physiological insulin response and reversal of IR in skeletal muscles.


Retinotopic sensitisation to spatial scale: evidence for flexible spatial frequency processing in scene perception.
Observers can use spatial scale information flexibly depending on categorisation task and on their prior sensitisation. Here, we explore whether attentional modulation of spatial frequency processing at early stages of visual analysis may be responsible. In three experiments, we find that observers' perception of spatial frequency (SF) band-limited scene stimuli is determined by the SF content of images previously experienced at that location during a sensitisation phase. We conclude that these findings are consistent with the involvement of relatively early, retinotopically mapped, stages of visual analysis, supporting the attentional modulation of spatial frequency channels account of sensitisation effects.


Simultaneous assessment of endothelial function and morphology in the brachial artery using a new semiautomatic ultrasound system.
The accuracy of measurements of the intima-media thickness (IMT) and flow-mediated dilatation (FMD) of the brachial artery made using a new semiautomated ultrasound system and the relationships among those parameters and the Framingham Risk Score (FRS) as a predictor of coronary heart disease (CHD) are unknown. We enrolled 70 subjects, including 47 patients with cardiovascular risk factors and 23 normal healthy volunteers. IMT and FMD were simultaneously measured using a new semiautomated ultrasound system, and the measurements were compared with those obtained manually as a reference standard (study 1). In addition, we enrolled 200 consecutive patients with risk factors but no CHD to examine the relationships among IMT, FMD and the FRS. The optimal cutoff values of FMD and IMT were determined in 200 patients without CHD, and the subjects were classified into four groups. The 10-year Framingham risks for each group were compared (study 2). FMD and IMT measurements made using the new semiautomated ultrasound system showed a good correlation with the measurements determined manually (study 1). Furthermore, FMD and IMT showed a significant correlation with the FRS. The 10-year Framingham risk was markedly higher in group D (FMD <5.5% and IMT >0.3 mm; 19.0±11.3%; study 2). In conclusion, the measurements made using a new semiautomated ultrasound system provided reliable and simultaneous evaluations of IMT and FMD. The combination of IMT and FMD measurements of the brachial artery may be beneficial for risk stratification of patients with cardiovascular risk factors but no CHD.


Immunohistochemical localization of avian pancreatic polypeptide-like immunoreactivity in the rat hypothalamus.
The distribution of avian pancreatic polypeptide-like (APP) immunoreactivity within the rat hypothalamus was investigated with the indirect immunoperoxidase method. APP immunoreactive perikarya are found in largest numbers in the retrochiasmatic area, the arcuate nucleus, and the supracommissural portion of the interstitial nucleus of the stria terminalis. Small clusters of immunoreactive neurons are also consistently observed in the ventral aspect of the medial preoptic area and lateral hypothalamic area, immediately dorsolateral to the optic chiasm and tracts. These neurons are apparent in all animals but are more intensely strained and occur in larger numbers following colchicine pretreatment. Other immunoreactive neurons are visible only in colchine-treated rats and are scattered throughout the anterior and lateral hypothalamic areas and the supramammillary nucleus. Immunoreactive axons and terminal fields present an extensive and highly characteristic distribution throughout the hypothalamus, which in many instances exhibits differential distribution within specific subfields of hypothalamic nuclei and areas. The heaviest concentrations of APP immunoreactive axons are present in the periventricular nucleus throughout the rostrocaudal extent of the hypothalamus, the ventrolateral portion of the suprachiasmatic nucleus, the retrochiasmatic area, the parvocellular paraventricular nucleus, the ventral supraoptic nucleus, the perifornical nucleus, the ventral dorsomedial nucleus, and the arcuate nucleus. Moderate plexuses of immunoreactive fibers are also present in the medial preoptic area, the anterior and lateral hypothalamic areas, the nucleus circularis, the median eminence, and the ventral premammillary area. Other areas, such as the ventromedial nucleus, contain virtually no immunoreactive axons but are encapsulated by a dense plexus of immunoreactive terminals. The distribution of a major component of APP immunoreactive fibers exhibits a marked similarity to that of previously described norepinephrine-containing hypothalamic afferents. Other groups of APP immunoreactive perikarya and fibers appear to represent components of intrinsic diencephalic systems.


Partnering with families known to child protection in an interprofessional context.
To meet the diverse needs of children and their families known to child protection, interprofessional collaboration across a range of services is critical. Children and their parents/caregivers are key stakeholders in these collaborations and current research highlights the need to strengthen their participation in these service responses. Practitioners have a critical role in strengthening family member participation in child welfare and protection responses. To explore professional's experiences and perceptions of working in partnership with children and families known to child protection in an interprofessional context. 14 professionals with extensive experience in the fields of family support and child protection. Semi-structured interviews were completed, recorded, transcribed, and then coded using NVivo 12 Pro. Reflexive thematic analysis was used to guide data analysis. Trusting practitioner-family relationships were affirmed to be critical to engaging and partnering with families. Results pertaining to the interprofessional context encourage a more community-oriented perspective of practitioner-family relationships, where practitioners have a collective responsibility to welcome families into an integrated network of community services. Further, the conflict for child protection practitioners between their legislated role and their need to build trusting relationships with families to support partnered work is discussed. The centrality of practitioner-family relationships needs to be better recognized and supported in policy and practice across all sectors supporting children and families known to child protection. An interprofessional approach to building practitioner-family relationships across this range of services may enhance family engagement and partnerships in their service responses.


Bridging the brain-mind divide in psychiatric education: The neuro-bio-psycho-social formulation.
Psychiatrists of the future need to have a strong working knowledge of the organ they work with-the brain. Neuropsychiatry is now more than a paradigm. Systems-level behavioral neuroscience, while still evolving, is mature enough to provide circuit-based foundation. Cellular and molecular neuroscience is starting to yield further mechanistic understanding. It is important to integrate such approaches into an evidence-based, bio-psycho-social formulation, with increasing implications for disease taxonomy, diagnosis and treatment.


[Preliminary radiation hygiene evaluation of the meat of animals whose feed was supplemented with mine water].
Experiments were conducted on pigs given mine water as a salt additive to their food ration. The passing of radioactive substances from the mine water into the muscle and bone tissues of the animals was studied. It was shown that the levels of Sr-90, Cs-137, Ra-226 and U entering the body with the meat of pigs receiving food with mine salt water were significantly lower than their annual ingress limits.


Tri-axial ellipsoids as models for macromolecules in solution: procedures for numerical inversion of the shape functions leading to a stable unique solution.
Two FORTRAN IV algorithms are given for determining the two axial ratios of a macromolecule (as modelled by a tri-axial ellipsoid) from its hydrodynamic parameters. The first involves a simple graphical inversion procedure of the volume independent V and R functions but can only be applied to a restricted range of macromolecules. The second algorithm is more general and involves an R-function constrained non-linear least squares fit to birefringence decay data.


Arginine methylation of the cellular nucleic acid binding protein does not affect its subcellular localization but impedes RNA binding.
Cellular nucleic acid binding protein (CNBP) contains seven zinc finger (ZF) repeats and an arginine and glycine (RG) rich sequence between the first and the second ZF. CNBP interacts with protein arginine methyltransferase PRMT1. Full-length but not RG-deleted or mutated CNBP can be methylated. Treatment with a methylation inhibitor AdOx reduced CNBP methylation, but did not affect the concentrated nuclear localization of CNBP. Nevertheless, arginine methylation of CNBP appeared to interfere with its RNA binding activity. Our findings show that arginine methylation of CNBP in the RG motif did not change the subcellular localization, but regulated its RNA binding activity.


Ultrasonic findings in polycystic ovarian disease.
The uterus and ovaries of 50 patients with polycystic ovarian disease (PCOD) and 30 eumenorrheic women were studied with a real-time ultrasound mechanical sector scanner. Uterine and ovarian volumes (UV and OV) and the OV/UV ratio were calculated, and ovarian morphology was classified as prevalently solid and cystic. Both ovaries were displayed in 44 of the PCOD and in 25 of the normal patients and appeared bilaterally solid, cystic, or with different morphology, respectively, in 43.2%, 47.7%, and 9.1% of cases in the former group and in 76%, 20%, and 4% in the latter group. Statistically significant differences between normal and PCOD patients were found in OV, UV, and OV/UV ratio. Bilaterally enlarged ovaries with multiple tiny cysts, the classic ultrasonographic picture of the polycystic ovary, were found in only 16 (36.3%) of the PCOD cases, while 34 (77.3%) had an OV/UV ratio greater than 1 standard deviation above the mean. Four ultrasonographic ovarian patterns were observed in the PCOD patients: enlarged cystic; enlarged solid; normal-sized cystic; and normal-sized solid. These findings emphasize the need for a reconsideration of the ultrasonographic criteria of PCOD.


New Concepts in Complex Regional Pain Syndrome.
Despite the severe pain and disability associated with complex regional pain syndrome (CRPS), the lack of understanding of the pathophysiological mechanisms supporting this enigmatic condition prevents the rational design of new therapies, a situation that is frustrating to both the physician and the patient. The review highlights some of the mechanisms thought to be involved in the pathophysiology of CRPS in preclinical models and CRPS patients, with the ultimate goal that understanding these mechanisms will lead to the design of efficacious, mechanism-based treatments available to the clinic.


Atomistic measurement and modeling of intrinsic fracture toughness of two-dimensional materials.
Quantifying the intrinsic mechanical properties of two-dimensional (2D) materials is essential to predict the long-term reliability of materials and systems in emerging applications ranging from energy to health to next-generation sensors and electronics. Currently, measurements of fracture toughness and identification of associated atomistic mechanisms remain challenging. Herein, we report an integrated experimental-computational framework in which in-situ high-resolution transmission electron microscopy (HRTEM) measurements of the intrinsic fracture energy of monolayer MoS2 and MoSe2 are in good agreement with atomistic model predictions based on an accurately parameterized interatomic potential. Changes in crystalline structures at the crack tip and crack edges, as observed in in-situ HRTEM crack extension tests, are properly predicted. Such a good agreement is the result of including large deformation pathways and phase transitions in the parameterization of the inter-atomic potential. The established framework emerges as a robust approach to determine the predictive capabilities of molecular dynamics models employed in the screening of 2D materials, in the spirit of the materials genome initiative. Moreover, it enables device-level predictions with superior accuracy (e.g., fatigue lifetime predictions of electro- and opto-electronic nanodevices).


Nonsurgical management of complicated splenic rupture in infectious mononucleosis.
We report on a 35-year-old man who presented to the emergency department with acute abdominal pain, postural hypotension, and tachycardia after having been diagnosed with Epstein-Barr virus infection 1 week before. Abdominal ultrasound and computed tomography revealed splenic rupture, and the patient underwent successful proximal angiographic embolization of the splenic artery. The course was complicated by painful splenic necrosis and respiratory insufficiency due to bilateral pleural effusions. Six weeks later, he additionally developed severe sepsis with Propionibacterium granulosum due to an intrasplenic infected hematoma, which required drainage. All complications were treated without surgical splenectomy, and the patient finally made a full recovery.


Anti-CRISPR prediction using deep learning reveals an inhibitor of Cas13b nucleases.
As part of the ongoing bacterial-phage arms race, CRISPR-Cas systems in bacteria clear invading phages whereas anti-CRISPR proteins (Acrs) in phages inhibit CRISPR defenses. Known Acrs have proven extremely diverse, complicating their identification. Here, we report a deep learning algorithm for Acr identification that revealed an Acr against type VI-B CRISPR-Cas systems. The algorithm predicted numerous putative Acrs spanning almost all CRISPR-Cas types and subtypes, including over 7,000 putative type IV and VI Acrs not predicted by other algorithms. By performing a cell-free screen for Acr hits against type VI-B systems, we identified a potent inhibitor of Cas13b nucleases we named AcrVIB1. AcrVIB1 blocks Cas13b-mediated defense against a targeted plasmid and lytic phage, and its inhibitory function principally occurs upstream of ribonucleoprotein complex formation. Overall, our work helps expand the known Acr universe, aiding our understanding of the bacteria-phage arms race and the use of Acrs to control CRISPR technologies.


Speech-Language Pathology production regarding voice in popular singing.
To present a literature review about the Brazilian scientific production in Speech-Language Pathology and Audiology regarding voice in popular singing in the last decade, as for number of publications, musical styles studied, focus of the researches, and instruments used for data collection. Cross-sectional descriptive study carried out in two stages: search in databases and publications encompassing the last decade of researches in this area in Brazil, and reading of the material obtained for posterior categorization. The databases LILACS and SciELO, the Databasis of Dissertations and Theses organized by CAPES, the online version of Acta ORL, and the online version of OPUS were searched, using the following uniterms: voice, professional voice, singing voice, dysphonia, voice disorders, voice training, music, dysodia. Articles published between the years 2000 and 2010 were selected. The researches found were classified and categorized after reading their abstracts and, when necessary, the whole study. Twenty researches within the proposed theme were selected, all of which were descriptive, involving several musical styles. Twelve studies focused on the evaluation of the popular singer's voice, and the most frequently used data collection instrument was the auditory-perceptual evaluation. The results of the publications found corroborate the objectives proposed by the authors and the different methodologies. The number of studies published is still restricted when compared to the diversity of musical genres and the uniqueness of popular singer.


Immune response to second vaccination series of hepatitis B virus among booster dose non-responders.
To evaluate the response to second vaccination series among post-booster sero-negative children who had previously received compulsory HBV vaccination. After given a booster dose to 1070 children, 103 of them failed to generate anamnestic response (anti-HBs <10 IU/L). Only 91/103 children received additional two doses of recombinant HBV vaccine (i.e. 2(nd) vaccination series) after 1 and 6 months post-booster. Blood sample was withdrawn aseptically one month later for quantitative assessment of anti-HBs to detect development of protective immune response (≥10 IU/L). Immunological vaccination failure was assigned to children who did not develop protective immune response after 2(nd) vaccination series. Protective immune response was detected among 84/91 children (92.3%). While 7/91 (7.7%) whose age were ≥10 years did not respond and had post-booster undetectable anti-HBs. About 80% of children with post-booster detectable anti-HBs showed significant protective immune response (anti-HBs ≥100 IU/L) and higher GMT (299.1 ± 3.6 IU/L) compared to those with undetectable 60% and 106.2 ± 12.9 IU/L respectively (P<0.05). No significant difference was detected as regards gender or residence, P>0.05. All children with history of rheumatic fever (7 children) or diabetes mellitus (1 child) developed immune response after 2(nd) vaccination series. A booster dose of HB vaccine may be unable to induce sufficient immunological response in children who had undetectable anti-HBs titers. Revaccination for non-responders is an important procedure to increase HBV protection rate.


Health Care Access and Service Use Among Behavioral Risk Factor Surveillance System Respondents Engaging in High-Risk Sexual Behaviors, 2016.
Access to health care services such as screening, testing, and treatment of sexually transmitted diseases is vital for those who engage in high-risk behaviors. Studies examining the relationship between high-risk behaviors and health care access and utilization are crucial for determining whether persons at risk are receiving appropriate health services. We examined 2016 data from the Behavioral Risk Factor Surveillance System. Our study population included persons aged 18 to 65 years. χ and logistic regression analyses were used to examine relationships between high-risk behaviors including drug use and high-risk sexual behaviors, and access to and utilization of health care services. Among our study population, 6.2% engaged in a high-risk behavior in the past year. Those engaging in high-risk behaviors were more likely to have no health insurance coverage (odds ratio [OR], 1.23; 95% confidence interval [CI], 1.13-1.34), have no personal health care provider (OR, 1.14; 95% CI, 1.06-1.21), have foregone care because of cost (OR 1.54; 95% CI, 1.42-1.65), or have had no routine check-up in the past 2 years (OR 1.16; 95% CI, 1.09-1.25). Those who engaged in high-risk behaviors had poorer health care access and utilization outcomes. Future studies should incorporate the relationships between changes in behaviors, health care access and utilization, and resulting sexually transmitted disease morbidity.


Vanadate enhances transformation of bovine papillomavirus DNA-transfected C3H/10T1/2 cells.
Bovine papillomavirus (BPV) DNA-transfected C3H/10T1/2 cells respond to tumor promoters by enhanced production of transformed foci. Vanadate, a suspected carcinogen, is a mitogen, generates active oxygen species and alters phosphorylation of proteins. We investigated whether vanadate would enhance transformation of BPV DNA-transfected C3H/10T1/2 cells. Transformed foci in BPV DNA transfected C3H/10T1/2 cells exposed continuously to vanadate for 21 days increased in a dose-dependent manner to 50-fold at 4 microM vanadate. This increase was not due to enhanced uptake of BPV DNA post transfection. Neither catalase nor superoxide dismutase inhibited the vanadate-mediated increase in transformed foci but this does not necessarily rule out the involvement of intracellular active oxygen species. At vanadate concentrations greater than 6 microM, cells lost adherence to the Petri plates. We conclude that vanadate is capable of enhancing BPV DNA-mediated cell transformation. Possible mechanisms may involve active oxygen species or altered patterns of protein phosphorylation.


Acanthamoeba keratitis during orthokeratology.
To report an infectious complication of overnight rigid gas-permeable contact lenses. Case report and medical literature review. A 16-year-old girl developed laboratory-confirmed acanthamoebic keratitis during orthokeratology for myopic reduction. Recent case reports suggest that Acanthamoeba is a cause of microbial keratitis associated with gas-permeable contact lenses among teenagers and young adults undergoing orthokeratology. Acanthamoeba keratitis is an emerging complication of orthokeratology in young myopes.


Loss of pectin is an early event during infection of cocoyam roots by Pythium myriotylum.
Cocoyam (Xanthosoma sagittifolium) is an important tuber crop in most tropical zones of Africa and America. In Cameroon, its cultivation is hampered by a soil-borne fungus Pythium myriotylum which is responsible for root rot disease. The mechanism of root colonisation by the fungus has yet to be elucidated. In this study, using microscopical and immunocytochemical methods, we provide a new evidence regarding the mode of action of the fungus and we describe the reaction of the plant to the early stages of fungal invasion. We show that the fungal attack begins with the colonisation of the peripheral and epidermal cells of the root apex. These cells are rapidly lost upon infection, while cortical and stele cells are not. Labelling with the cationic gold, which binds to negatively charged wall polymers such as pectins, is absent in cortical cells and in the interfacial zone of the infected roots while it is abundant in the cell walls of stele cells. A similar pattern of labelling is also found when using the anti-pectin monoclonal antibody JIM5, but not with anti-xyloglucan antibodies. This suggests that early during infection, the fungus causes a significant loss of pectin probably via degradation by hydrolytic enzymes that diffuse and act away from the site of attack. Additional support for pectin loss is the demonstration, via sugar analysis, that a significant decrease in galacturonic acid content occurred in infected root cell walls. In addition, we demonstrate that one of the early reactions of X. sagittifolium to the fungal invasion is the formation of wall appositions that are rich in callose and cellulose.


A delay in the diagnosis of colorectal cancer screened by fecal immunochemical tests during the COVID-19 pandemic: a longitudinal cohort study.
There is concern that the COVID-19 pandemic may cause people to refrain from undergoing examination resulting in delayed detection of colorectal cancer (CRC). The purpose of this study was to investigate whether there was a delay in CRC detection due to withholding of screening. The colonoscopy screening rate and the CRC detection rate were calculated for patients who underwent fecal immunochemical tests (FITs) from 2018 to 2021 in the longitudinal cohort. The stages of CRC cases detected as a result of positive FIT in each year were compared. A total of 39,521 patients were initially screened by FIT over a 4-year period. The FIT-positive rate was 4.7% (441 /9,349) in 2018, 4.6% (420 /9,156) in 2019, 4.9% (453 /9,255) in 2020, and 4.3% (504 /11,760) in 2021. The colonoscopy screening rate for positive FIT results was lower in 2020 than in 2019 (25.8% vs. 38.1%, P < 0.001), and higher in 2021 than in 2020 (56.7% vs. 25.8%, P < 0.001). The CRC detection rate among colonoscopy recipients was higher in 2021 than in 2020 (13% vs. 4%, P = 0.014). Stage 1 or higher CRC accounted for 25.0% (1/4) in 2020, and 78% (18/23) in 2021. Among the CRC cases detected each year, 1 (14%), 1 (25%), and 10 (43%) did not undergo colonoscopy despite positive FIT results in the previous year. The COVID-19 pandemic has reduced the detection of CRC by screening colonoscopy following FIT and might have led to a delay in the detection of CRC.


A pH-dependent bolt involving cytosine bases located in the lateral loops of antiparallel G-quadruplex structures within the SMARCA4 gene promotor.
Some lung and ovarian tumors are connected to the loss of expression of SMARCA4 gene. In its promoter region, a 44-nucleotides long guanine sequence prone to form G-quadruplex structures has been studied by means of spectroscopic techniques (circular dichroism, molecular absorption and nuclear magnetic resonance), size exclusion chromatography and multivariate analysis. The results have shown that the central 21-nucleotides long sequence comprising four guanine tracts of disparate length is able to fold into a pH-dependent ensemble of G-quadruplex structures. Based on acid-base titrations and melting experiments of wild and mutated sequences, the formation of a C·C+ base pair between cytosine bases present at the two lateral loops is shown to promote a reduction in conformational heterogeneity, as well as an increase in thermal stability. The formation of this base pair is characterized by a pKa value of 7.1 ± 0.2 at 20 °C and 150 mM KCl. This value, higher than those usually found in i-motif structures, is related to the additional stability provided by guanine tetrads in the G-quadruplex. To our knowledge, this is the first thermodynamic description of this base pair in loops of antiparallel G-quadruplex structures.


Sigmoid colon schwannoma difficult to distinguish from peritoneal dissemination 13 years after pancreatic neuroendocrine tumor surgery.
Schwannoma, which clinicians sometimes struggle to diagnose, is a tumor arising from Schwann cells of peripheral nerves, often in the soft tissues and rarely in the gastrointestinal tract. Pancreatic neuroendocrine tumor (PNET) is rare among pancreatic tumors, and recurrence can occur long after resection. Here, we were presented with a case where a sigmoid colon schwannoma was difficult to distinguish from a postoperative recurrence of PNET and was diagnosed after laparoscopic resection. A 51-year-old man was diagnosed with PNET (NET G2) after a distal pancreatectomy (DP) 13 years ago. The patient underwent hepatectomy due to liver metastasis 12 years after initial radical surgery. The follow-up magnetic resonance imaging (MRI) after hepatectomy showed pelvic nodules, and laparoscopic surgery was performed for both diagnosis and treatment because peritoneal dissemination of PNET could not be ruled out. Since the tumor was in the sigmoid colon, a partial colon resection was performed. The histopathological diagnosis was a schwannoma, and the patient was discharged on the seventh postoperative day. We experienced a case of sigmoid colon schwannoma that was difficult to differentiate from peritoneal dissemination of PNET and was later diagnosed after laparoscopic resection. In addition, this case involved a long-term postoperative recurrence of PNET that was amenable to radical resection, further establishing the importance of long-term imaging follow-up.


Schisandra chinensis Oil Attenuates Aristolochic Acid I-Induced Nephrotoxicity in vivo and in vitro.
To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism. C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry. SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01). SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.


Expanded phase II trial of paclitaxel in metastatic breast cancer: a Southwest Oncology Group study.
The study was designed to evaluate the efficacy of paclitaxel in metastatic breast cancer patients. The design was motivated by a report from FDA and NCI staff proposing assessment of pre- and post-treatment symptoms as a means of evaluating treatment effectiveness [1]. Patients with symptomatic and/or measurable metastatic breast cancer with prior treatment received paclitaxel 210 mg/m2 as a 3 hour infusion every three weeks until toxicity or progression. A unique endpoint was subjective symptomatic response, defined as an improvement in the Symptom Distress Scale score by > or = 3 points at two successive evaluations before treatment failure. Patients were also evaluated for objective response and toxicity. Of 135 patients registered, 123 were eligible and treated. The subjective symptomatic response rate for 93 symptomatic patients who completed forms was 40%, 95% confidence interval 29-51%. The objective response rate in 77 patients with measurable disease was 19%, 95% confidence interval 11-30%. In patients with both measurable and symptomatic disease, 37% had symptomatic and 13% had objective responses. Median times to treatment failure and death were 4 and 11 months, respectively. Toxicity was greater than anticipated: 12% discontinued treatment due to toxicity, 29% developed at least one Grade 3 neuromuscular toxicity, and two patients died of sepsis while neutropenic. Paclitaxel by 3 hour infusion at a dose of 210 mg/m2 produced excessive neurotoxicity in patients with previously treated metastatic breast cancer. Both sustained subjective symptom reduction and objective responses were demonstrated, but dose reduction for routine practice is recommended.


Sintering effects on the strength of hydroxyapatite.
Mechanisms underlying temperature-strength interrelations for dense (> 95% dense, pores closed) hydroxyapatite (HAp) were investigated by comparative assessment of temperature effects on tensile strength, Weibull modulus, apparent density, decomposition (HAp:tricalcium phosphate ratio), dehydroxylation and microstructure. Significant dehydroxylation occurred above approximately 800 degrees C. Strength peaked at approximately 80 MPa just before the attainment of closed porosity (approximately 95% dense). For higher temperatures (closed porosity), the strength dropped sharply to approximately 60 MPa due to the closure of dehydroxylation pathways, and then stabilized at approximately 60 MPa. At very high temperatures (> 1350 degrees C), the strength dropped catastrophically to approximately 10 MPa corresponding to the decomposition of HAp to tricalcium phosphate and the associated sudden release of the remaining bonded water.


Bone age and onset of puberty in normal boys.
Many conditions that delay skeletal maturation also delay the onset of puberty, whereas conditions that accelerate skeletal maturation often hasten the onset puberty, raising the possibility that skeletal maturation influences pubertal onset. To determine whether this concordance is also present in normal children, we analyzed data from 30 normal boys participating in a longitudinal study. Height, weight, and serum testosterone concentrations were assessed every 6 months and bone age (Fels method) every year. Pubertal onset was defined by serum testosterone > or =30 ng/dL. The variability in bone age at onset of puberty was not less than the variability in chronological age. In addition, there was no significant correlation between skeletal advancement and pubertal advancement (r=0.01, P=0.9). Similarly, there was not a significant correlation between pubertal advancement and height age advancement, weight age advancement, or BMI age advancement. Our findings do not support the hypothesis that skeletal maturation directly influences the age of pubertal onset in normal boys.


Corrigendum: Absence of Behavioral Harm Following Non-efficacious Sexual Orientation Change Efforts: A Retrospective Study of United States Sexual Minority Adults, 2016-2018.
[This corrects the article DOI: 10.3389/fpsyg.2022.823647.].


Escherichia coli proton-translocating F0F1-ATP synthase and its association with solute secondary transporters and/or enzymes of anaerobic oxidation-reduction under fermentation.
The Escherichia coli proton-translocating F0F1-ATP synthase has a priority in H+ circulation through the membrane in maintaining proton-motive force in the context of ATP synthesis and hydrolysis. Recent advances in the study of this complex under fermentative growth have led to hypothesis that, in the absence of oxidative phosphorylation, F0F1 is implicated as an essential part of H+ movement and ATP hydrolysis, associated with solute secondary transporters and/or enzymes of anaerobic oxidation-reduction. These associations can result from a protein-protein interaction by dithiol-disulfide interchange. In such associations F0F1 has novel functions in bacterial cell physiology.