[Foreskin retraction for phimosis of the newborn].
No guideline exists on how to treat boy's phimosis. We examined if retraction of the foreskin of the newborn boy's penis could make true phimosis become false phimosis. We taught the mother to retract the foreskin and keep inside the foreskin clean. Exposure degree of glans by retraction of foreskin was defined in 7 grades, 0 (none) approximately III (middle) approximately VI (full). Of the 538 newborn examined, none had full exposure (VI). All of the 372 cases who continued the procedure, including 2 buried penis, gained full exposure (VI). Average time for full exposure according to the first degree of exposure was 2.94 months (0), 1.78 months (III), 1.22 months (V), 2.32 months average, respectively. No serious complications occurred. Retraction of the foreskin from the newborn period made all the true phimosis to be false phimosis and operative procedures became unnecessary.


Rapid Conversion to Telemental Health Services in Response to COVID-19: Experiences of Two Outpatient Mental Health Clinics.
Background: The COVID-19 pandemic triggered changes across health care systems, with many sectors seeing significant drops in patient visits. Rapid transition to telemental health (TMH) allowed for the continued delivery of mental health care. Although several guidelines and best practices are available for the methodical development of a TMH service, there are few documented procedures on rapidly converting to fully virtualized services. We discuss how two outpatient mental health clinics at the University of Colorado Anschutz Medical Campus rapidly virtualized clinical services during the COVID-19 pandemic. Methods: All current clinical appointments were converted to virtual, and all new clinical intakes were scheduled as virtual visits starting March 16, 2020. Virtualization included a modified needs assessment, updated clinic procedures, focused patient and staff training on TMH, and increased frequency of team meetings. We conducted a retrospective evaluation of clinic log and electronic health record data to examine the number of appointments and no-shows before and after COVID-19 virtualization. Results: Virtualization was operational within two business days. Scheduled appointments decreased 10.6% immediately postvirtualization, followed by an increase of 17.8% across the 6 months postvirtualization. No-show rates dropped from 11.9% pre- to 6.8% postvirtualization, leading to a 26.2% increase in completed visits. Discussion: Rapid virtualization of mental health services can occur effectively. Wider use and acceptance of TMH, especially to patient-homes, is likely in the foreseeable future as health care providers and systems reconceptualize service delivery. Future research must include analyzing the impact such changes make on clinical outcomes and patient visit volumes.


Assessment of the micronucleus assay as a biological dosimeter using cytokinesis-blocked lymphocytes from cancer patients receiving fractionated partial body-radiotherapy.
To assess the suitability of the cytokinesis block micronucleus assay as a biological dosimeter following in-vivo radiation using cancer patients undergoing radiotherapy. Blood from 4 healthy donors was irradiated in vitro with gamma-rays and the dose response of induced micronuclei in binucleate lymphocytes following cytokinesis block was determined. Micronucleus frequency was ascertained before and at intervals during radiotherapy treatment in 6 patients with various tumors in the pelvic region. Equivalent whole body doses (physical doses) at these times were calculated from radiation treatment plans and cumulative dose volume histograms. Linear dose response relationships were found for induced micronucleus frequency in lymphocytes resulting from both in-vitro and in-vivo irradiation. Doses resulting from in-vivo irradiation (biological doses) were estimated by substitution of micronucleus frequency observed in radiotherapy patients into the dose response curve from in-vitro irradiation of blood. The relationship between the biologically estimated dose (BD) and the calculated equivalent whole body dose (PD) was BD = 0.868 (+/- 0.043)PD + 0.117 (+/- 0.075). The micronucleus assay appears to offer a reliable and consistent method for equivalent whole body radiation dose estimation, although our findings should be confirmed using lymphocytes from radiotherapy patients with tumors at anatomical sites other than the pelvis. Except at doses lower than about ).4 Gy, the method yields dose estimates acceptably close to "true" physically determined doses. The assay can be performed relatively rapidly and can be used as a "first line" biological dosimeter in situations where accidental exposure to relatively high radiation doses has occurred.


Experimental evidence for the role of sexual selection in the evolution of cuticular hydrocarbons in the dung beetle, Onthophagus taurus.
A role for sexual selection in the evolution of insect cuticular hydrocarbons (CHCs) is suggested by observations of selection acting on male CHCs during female mate choice. However, evidence that CHCs evolve in response to sexual selection is generally lacking, and there is a need to extend our understanding beyond well-studied taxa. Experimental evolution offers a powerful approach to investigate the effect of sexual selection on the evolution of insect CHCs. We conducted such an experiment using the dung beetle, Onthophagus taurus. After six, 12 and 21 generations of experimental evolution, we measured the CHCs of beetles from three populations subject to sexual selection and three populations within which sexual selection had been removed via enforced monogamy. We found that the male CHC profile responded to the experimental removal of sexual selection. Conversely, the CHC profile of females responded to the presence of sexual selection but not to its removal. These results show that sexual selection can be an important mechanism affecting the evolution of insect CHCs and that male and female CHCs can evolve independently.


The effect of theta-burst TMS on cognitive control networks measured with resting state fMRI.
IT HAS BEEN PROPOSED THAT TWO RELATIVELY INDEPENDENT COGNITIVE CONTROL NETWORKS EXIST IN THE BRAIN: the cingulo-opercular network (CO) and the fronto-parietal network (FP). Past work has shown that chronic brain lesions affect these networks independently. It remains unclear, however, how these two networks are affected by acute brain disruptions. To examine this, we conducted a within-subject theta-burst transcranial magnetic stimulation (TBS) experiment in healthy individuals that targeted left anterior insula/frontal operculum (L aI/fO, a region in the CO network), left dorsolateral prefrontal cortex (L dlPFC, a region in the FP network), or left primary somatosensory cortex (L S1, an experimental control region). Functional connectivity (FC) was measured in resting state fMRI scans collected before and after continuous TBS on each day. We found that TBS was accompanied by generalized increases in network connectivity, especially FP network connectivity, after TBS to either region involved in cognitive control. Whole-brain analyses demonstrated that the L dlPFC and L aI/fO showed increased connectivity with regions in frontal, parietal, and cingulate cortex after TBS to either L dlPFC or L aI/fO, but not to L S1. These results suggest that acute disruption by TBS to cognitive control regions causes widespread changes in network connectivity not limited to the targeted networks.


Stem-loop induced ribosome queuing in the uORF2/ ATF4 overlap fine-tunes stress-induced human ATF4 translational control.
ATF4 is a master transcriptional regulator of the integrated stress response leading cells towards adaptation or death. Since its discovery, the delayed translation reinitiation mechanism, with reinitiation-permissive uORF1 playing a key role, was thought to underlie the ATF4 stress-induced upregulation. However, mounting evidence challenging this mechanism as the sole source of ATF4 translation control prompted us to investigate additional means of its regulation. Contrasting the original model, we show that inhibitory uORF2 is inducible and translated even under stress; that it encompasses two post-transcriptionally modified adenines performing antagonistic roles; and that the canonical ATF4 translation start site is robustly leaky-scanned. Most importantly, we demonstrate that the presence of a stable stem-loop in the uORF2/ ATF4 overlap, immediately preceded by near-cognate CUG, introduces another layer of regulation in the form of ribosome queuing. Thus, ATF4 translational control is much more complex than originally described underpinning its key role in diverse biological processes.


Three-Dimensional Nanoscale Nuclear Architecture Mapping of Rectal Biopsies Detects Colorectal Neoplasia in Patients with Inflammatory Bowel Disease.
Patients with inflammatory bowel disease (IBD) colitis are at an increased risk of developing colorectal cancer and are currently recommended to undergo extensive annual or biennial colonoscopy, a costly and invasive procedure. Most surveillance colonoscopies are negative with no existing objective measures for assessing their risk of developing cancer. We have recently developed a less invasive, cost-effective and objective method to assess cancer risk by detecting the presence of colonic neoplasia via 3-dimensional (3D) nanoscale nuclear architecture mapping (nanoNAM) of normal-appearing rectal biopsies. To establish its translational relevance, we prospectively recruited 103 patients with IBD colitis undergoing surveillance colonoscopy and measured submicroscopic alterations in aberrant intrinsic nuclear architecture of epithelial cells from normal-appearing rectal biopsies with nanoNAM. The results were correlated with the histologic diagnoses from all random biopsies obtained during initial and follow-up colonoscopy within 3 years. Using nanoNAM-based structural characterization as input features into a soft margin-based ν-SVM risk classifier, we show that nanoNAM detects colonic neoplasia with AUC of 0.87 ± 0.04, sensitivity of 0.81 ± 0.09, and specificity of 0.82 ± 0.07 in the independent validation set. In addition, projecting nanoNAM features onto a 2-sphere reveals patients with low-risk and high-risk IBD colitis existing on separate hemispheres. Finally, we show that this ability to assess cancer risk translates to clinically-relevant estimation of individual-patient likelihood of being truly at risk. We demonstrate the potential of nanoNAM to identify patients with IBD at higher risk of developing cancer from normal-appearing rectum tissue, which may aid clinicians in patients with personalized IBD colitis surveillance.


Insight into mammalian selenocysteine insertion: domain structure and ribosome binding properties of Sec insertion sequence binding protein 2.
The cotranslational incorporation of the unusual amino acid selenocysteine (Sec) into both prokaryotic and eukaryotic proteins requires the recoding of a UGA stop codon as one specific for Sec. The recognition of UGA as Sec in mammalian selenoproteins requires a Sec insertion sequence (SECIS) element in the 3' untranslated region as well as the SECIS binding protein SBP2. Here we report a detailed analysis of SBP2 structure and function using truncation and site-directed mutagenesis. We have localized the RNA binding domain to a conserved region shared with several ribosomal proteins and eukaryotic translation termination release factor 1. We also identified a separate and novel functional domain N-terminal to the RNA binding domain which was required for Sec insertion but not for SECIS binding. Conversely, we showed that the RNA binding domain was necessary but not sufficient for Sec insertion and that the conserved glycine residue within this domain was required for SECIS binding. Using glycerol gradient sedimentation, we found that SBP2 was stably associated with the ribosomal fraction of cell lysates and that this interaction was not dependent on its SECIS binding activity. This interaction also occurred with purified components in vitro, and we present data which suggest that the SBP2-ribosome interaction occurs via 28S rRNA. SBP2 may, therefore, have a distinct function in selecting the ribosomes to be used for Sec insertion.


Hypermethylation of the inducible nitric-oxide synthase gene promoter inhibits its transcription.
Exuberant generation of nitric oxide (NO) by inducible nitric-oxide synthase (iNOS) can cause unintended injury to host cells during glomerulonephritis and other inflammatory diseases. Although much is known about the mechanisms of iNOS induction, few transcriptional repression mechanisms have been found. We explored the role of cytosine methylation in the regulation of iNOS transcription. Treatment of mesangial cells with DNA methylation inhibitors augmented cytokine induction of endogenous NO production and iNOS protein levels, as well as iNOS promoter activity. In a corresponding manner, in vitro methylation of the murine iNOS promoter was sufficient to silence its activity in mesangial cells. In contrast, antisense knockdown of DNA methyltransferase-3b expression and activity increased iNOS promoter activity and nitrite production. Bisulfite treatment and sequencing analysis of the iNOS promoter identified methylation of cytosines framing an enhancer element at -879/-871. In vitro methylation inhibited binding of NFkappaB p50 to this element, and deletion of the element resulted in relief of transcriptional repression. These results provide evidence for a unique molecular mechanism involved in transcriptional regulation of iNOS gene expression.


The Psychomotor Cognition Test for Measurement of Sleepiness/Fatigue on a Touch Screen.
The Psychomotor Vigilance Test (PVT) is a simple and reliable performance test that measures sustained attention, alertness level, and fatigue level. The PVT is a convenient tool that can be used in real time in situ through a mobile device without the assistance of experts and therefore can be used to improve safety and prevent accidents. However, the original PVT is vulnerable to the subject's intentional concentration on the test, and the variance range among tests is narrow; these factors limit its usefulness in classifying the level of fatigue. This study overcome these limitations and develop the Psychomotor Cognition Test (PCT) by transforming the PVT into a tool that stably classifies fatigue levels, still requiring a short period of time. In the PCT, compared to the PVT, reaction time is significantly longer, and success rate is significantly lower (both p<0.0001). Whereas reaction time and success rate of the PVT do not show a significant correlation with fatigue level, those of the PCT show significant correlations with fatigue level, respectively (p<0.001). This study suggests that the PCT can be used in real time in situ as a risk management tool for workers performing dangerous tasks and can become an even more powerful tool when combined with other physiological indicators.


The effect of temperature and pH on the motility and viability of ostrich sperm.
As the chemical environment of semen diluents can have a profound effect on sperm quality, we examined the effect of temperature and pH on the motility and viability of sperm in the ostrich. Semen was collected from four males, each male being replicated three times. Ejaculates were diluted and incubated for 10 min at 20°C and 40°C in four different buffers, temperature adjusted at pH 6, 7, 8 and 9 respectively. Average path velocity (VAP), curvilinear velocity (VCL), straight-line velocity (VSL), linearity (LIN), beat cross frequency (BCF) and amplitude of lateral displacement (ALH) were then recorded for each sample using CASA. The viability of sperm was assessed using nigrosin-eosin staining. Sperm incubated at 40°C had higher motility parameters, except for ALH. At 40°C, VAP, VSL and LIN increased with pH while VCL, BCF and ALH were higher for lower pHs. The viability of sperm was not affected by temperature but decreased at pH values>7. A pH in the neutral range appeared to yield higher quality sperm after in vitro storage at 20°C. However, the effect of different pH levels and temperatures on sperm longevity needs to be investigated further to develop viable ostrich specific diluents.


Synthetic Detergents: Their Influence upon Iron-Binding Complexes of Natural Waters.
Organic compounds extracted from Michigan lakes and streams and added to algal cultures increase the growth rate of the green alga (Chlamydomonas reinhardi) when iron is present. Two-dimensional paper chromatography has shown that the iron is complexed by organic fractions containing an amine group. When isolated from natural waters containing a concentration of over 0.3 part per million alkyl benzene sulfonate, these compounds do not show an iron-binding capacity. Separation of this sulfonate from the amine complexes restores the iron-binding capability. These findings suggest that detergents may influence the mobility of iron by reducing the number of binding sites, and in this way may have an important secondary effect upon the primary production of lakes and streams.


Radiculopathy caused by lumbar epidural venous varix: case report.
A 33-year-old man presented with a rare case of lumbar epidural venous varix causing radiculopathy manifesting as sciatica exacerbated during bowel movements. The left straight-leg raising test was positive and patellar tendon reflex was lost. Lumbar magnetic resonance imaging showed a mass lesion in the epidural space at the L4 level just anterior to the dural sac on the left, appearing as hypointense on T(1)- and hyperintense on T(2)-weighted images, with ring-like enhancement with gadopentetate dimeglumine. He underwent surgery under a preoperative diagnosis of cystic nerve sheath tumor. After left hemilaminectomy, intraoperative ultrasonography showed a low echoic mass lesion ventral to the L4 nerve root. The mass was dark blue with a smooth wall. Tearing of the wall resulted in continuous bleeding. After removal of the lesion, we confirmed that the dura of the nerve root was intact. Histological examination of the surgical specimen confirmed venous tissue. The postoperative course was excellent. Lumbar epidural varix is difficult to diagnose preoperatively. Lumbar epidural varix should be considered if the lesion is smaller on preoperative than intraoperative imaging, or disappears with bleeding cessation, as this may avoid unnecessary widening of the operative field. The correct preoperative diagnosis remains difficult, so we recommend surgical removal and histological confirmation.


Ecological Drivers of Carnivoran Body Shape Evolution.
AbstractMorphological diversity is often attributed as adaptations to distinct ecologies. Although biologists have long hypothesized that distinct ecologies drive the evolution of body shape, these relationships are rarely tested across macroevolutionary scales in mammals. Here, I tested hypotheses that locomotor, hunting, and dietary ecologies influenced body shape evolution in carnivorans, a morphologically and ecologically diverse clade of mammals. I found that adaptive models with ecological trait regimes were poor predictors of carnivoran body shape and the underlying morphological components that contribute to body shape variation. Instead, the best-supported model exhibited clade-based evolutionary shifts, indicating that the complexity and variation of body shape landscape cannot be effectively captured by a priori ecological regimes. However, ecological adaptations of body shapes cannot be ruled out, as aquatic and terrestrial carnivorans exhibited opposite allometric patterns of body shape that may be driven by different gravitational constraints associated with these different environments. Similar to body size, body shape is a prominent feature of vertebrate morphology that may transcend one-to-one mapping relationships between morphology and ecological traits, enabling species with distinct body shapes to exploit similar resources and exhibit similar ecologies. Together, these results demonstrate that the multidimensionality of both body shape morphology and ecology makes it difficult to disentangle the complex relationship among morphological evolution, ecological diversity, and phylogeny across macroevolutionary scales.


Serotonin transporter binding sites and mRNA levels in depressed persons committing suicide.
The serotonin transporter (5-HTT) has been found altered in postmortem brain samples from persons committing suicide, but the results of radioligand binding studies have been inconsistent. In the present series of experiments, autoradiographic radioligand binding and in situ hybridization techniques were utilized to examine 5-HTT function in the brains of 8 depressed subjects who had committed suicide, and matched controls. It was hypothesized that depressed subjects would demonstrate decreased numbers of 5-HTT binding sites and mRNA; however, [125I]RTI-55 binding to the 5-HTT was not different in the midbrain, hippocampus, or frontal cortex of depressed subjects. Also, 5-HTT mRNA levels in dorsal and median raphe nuclei were not different between controls and depressed subjects. The current results, although limited in scope because of the small number of subjects included, offer no evidence that alterations in the 5-HTT occur in pertinent brain regions of depressed individuals.


Role of cAMP and calcium influx in endothelin-1-induced ANP release in rat cardiomyocytes.
The mechanism of endothelin-1 (ET-1)-induced atrial natriuretic peptide (ANP) release was studied in neonatal rat ventricular cardiomyocytes. These cells expressed a single high-affinity class of ETA receptor (dissociation constant = 54 +/- 18 pM, n = 3), but no ETB receptors. Incubation of cardiomyocytes with ET-1 led to concentration-dependent ANP release and prostacyclin production. ET-1-induced ANP release was affected by neither protein kinase C (PKC) inhibition or downregulation nor by cyclooxygenase inhibition, indicating that ET-1-stimulated ANP secretion is not a PKC-mediated, prostaglandin-dependent process. Furthermore, ET-1 significantly stimulated adenosine 3',5'-cyclic monophosphate (cAMP) production and increased cytosolic calcium concentration in these preparations. Both ET-1-induced calcium influx and ANP release were decreased by the cAMP antagonist Rp-cAMPS, the Rp diastereoisomer of cAMP. Moreover, ET-1-induced ANP secretion was strongly inhibited in the presence of nifedipine as well as in the absence of extracellular calcium. Thus our results suggest that ET-1 stimulates ANP release in ventricular cardiomyocytes via an ETA receptor-mediated pathway involving cAMP formation and activation of a nifedipine-sensitive calcium channel.


Blockade of nicotine reward and reinstatement by activation of alpha-type peroxisome proliferator-activated receptors.
Recent findings indicate that inhibitors of fatty acid amide hydrolase (FAAH) counteract the rewarding effects of nicotine in rats. Inhibition of FAAH increases levels of several endogenous substances in the brain, including the endocannabinoid anandamide and the noncannabinoid fatty acid ethanolamides oleoylethanolamide (OEA) and palmitoylethanolamide, which are ligands for alpha-type peroxisome proliferator-activated nuclear receptors (PPAR-α). Here, we evaluated whether directly acting PPAR-α agonists can modulate reward-related effects of nicotine. We combined behavioral, neurochemical, and electrophysiological approaches to evaluate effects of the PPAR-α agonists [[4-Chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]acetic acid (WY14643) and methyl oleoylethanolamide (methOEA; a long-lasting form of OEA) on 1) nicotine self-administration in rats and squirrel monkeys; 2) reinstatement of nicotine-seeking behavior in rats and monkeys; 3) nicotine discrimination in rats; 4) nicotine-induced electrophysiological activity of ventral tegmental area dopamine neurons in anesthetized rats; and 5) nicotine-induced elevation of dopamine levels in the nucleus accumbens shell of freely moving rats. The PPAR-α agonists dose-dependently decreased nicotine self-administration and nicotine-induced reinstatement in rats and monkeys but did not alter food- or cocaine-reinforced operant behavior or the interoceptive effects of nicotine. The PPAR-α agonists also dose-dependently decreased nicotine-induced excitation of dopamine neurons in the ventral tegmental area and nicotine-induced elevations of dopamine levels in the nucleus accumbens shell of rats. The ability of WY14643 and methOEA to counteract the behavioral, electrophysiological, and neurochemical effects of nicotine was reversed by the PPAR-α antagonist 1-[(4-Chlorophenyl)methyl]-3-[(1,1-dimethylethyl)thio]-a,a-dimethyl-5-(1-methylethyl)-1H-Indole-2-propanoic acid (MK886). These findings indicate that PPAR-α might provide a valuable new target for antismoking medications.


Umbilical cord mesenchymal stem cells inhibited inflammation of bronchial epithelial cells by regulating Hedgehog pathway.
This study aimed to explore the role and mechanism of umbilical cord mesenchymal stem cells (UCMSCs) in regulating inflammation of bronchial epithelial cells. Transforming growth factor beta-1 (TGF-β1) was used to induce inflammation in human bronchial epithelial cells. Cell proliferation was detected through CCK8 and cell apoptosis was detected by Annexin V and propidium iodide double staining. E-cadherin and α-smooth muscle actin (α-SMA) were detected by immunofluorescence, and tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in culture medium supernatant were detected by ELISA. The expression of E-cadherin, α-SMA, Sonic hedgehog (Shh), Gli1 and Snail was detected by Western blot analysis. Compared with the control group, bronchial epithelial cells treated with TGF-β1 showed significantly decreased proliferation, increased apoptosis, increased secretion of TNF-α and IL-6, increased expression of α-SMA, Shh, Gli1 and Snail and decreased E-cadherin expression. However, co-culture with UCMSCs inhibited TGF-β1-induced changes in human bronchial epithelial cell proliferation, apoptosis, secretion of TNF-α and IL-6 and activation of the Hedgehog pathway. In conclusion, UCMSCs have protective effects on TGF-β1-induced inflammation in human bronchial epithelial cells by regulating the Hedgehog pathway.


Chemokine Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant.
Microbial infection is characterized by release of multiple proinflammatory chemokines that direct neutrophils to the insult site. How collective function of these chemokines orchestrates neutrophil recruitment is not known. Here, we characterized the role for heterodimer and show that the Cxcl1-Cxcl2 heterodimer is a potent neutrophil chemoattractant in mice and can recruit more neutrophils than the individual chemokines. Chemokine-mediated neutrophil recruitment is determined by Cxcr2 receptor signaling, Cxcr2 endocytosis, and binding to glycosaminoglycans. We have now determined heterodimer's Cxcr2 activity using cellular assays and Cxcr2 density in blood and recruited neutrophils in heterodimer-treated mice. We have shown that the heterodimer binds glycosaminoglycans with higher affinity and more efficiently than Cxcl1 or Cxcl2. These data collectively indicate that optimal glycosaminoglycan interactions and dampened receptor activity acting in concert in a dynamic fashion promote heterodimer-mediated robust neutrophil recruitment. We propose that this could play a critical role in combating infection.


LINC00963 Functions as an Oncogene in Bladder Cancer by Regulating the miR-766-3p/MTA1 Axis.
Long non-coding RNAs have been found to be involved in bladder cancer development. This article studied LINC00963 effects on bladder cancer progression to provide a novel treatment target. Totally 56 bladder cancer patients participated in this research. Bladder cancer cells were transfected. Cell counting kit 8 assay and clone formation experiment were used for cell viability and colony formation detection. Cell migration and invasion were determined by Transwell experiment. LINC00963 distribution was explored by cytoplasmic and nuclear extract isolation and quantitative real-time polymerase chain reaction. Luciferase reporter experiment and RNA pulldown experiment were performed to detect the relationship between these two genes. The cancer genome atlas analysis was used for the detection of metastasis-associated protein 1 (MTA1) expression in bladder cancer. LINC00963 was seriously up-regulated in bladder cancer patients. High LINC00963 expression indicated high histological grade and low survival. LINC00963 was obviously up-regulated in bladder cancer cells. Knockdown of LINC00963 significantly reduced bladder cancer cells viability, colony formation, migration and invasion. Luciferase reporter experiment and RNA pulldown experiment revealed that LINC00963 promoted MTA1 expression via directly inhibiting miR-766-3p. MTA1 was up-regulated in bladder cancer patients. MTA1 up-regulation reversed the inhibitory effect of LINC00963 knockdown on bladder cancer cell viability, migration and invasion. LINC00963 functions as an oncogene in bladder cancer by regulating the miR-766-3p/MTA1 axis.


The fall and rise of gonorrhoea incidence in Israel: an international phenomenon?
There is evidence of a recent resurgence of the incidence of gonorrhoea in some countries. To examine trends in gonorrhoea incidence in Israel and compare them with the United States and countries in Europe The 1967-2001 annual incidence of gonorrhoea in Israel was obtained from the Israel Ministry of Health's department of epidemiology and for the United States from summary reports of the Centers for Disease Control. The incidence of gonorrhoea in European countries was extracted from the World Health Organization, Health for All database. In Israel, following a long period of decline from 40 per 100 000 in 1970 to 0.74 per 100 000 in 1997, incidence rates began to increase in 1998 to 13.8 per 100 000 in 2001. This pattern parallels those observed in a number of European countries and to some extent, in the United States. Most reported morbidity in Israel occurs among males aged 20-44 years. The resurgence of gonorrhoea does not appear to be explained solely by behavioural changes. Transmission of the disease should be further studied among different subpopulations in order to develop new prevention strategies.


Aging-associated increase in intestinal absorption of macromolecules.
The intestinal permeability of aging rats to various molecular weight species of polyethylene glycol 400 (PEG 400) was studied. Animals received a bolus of PEG 400 by oral gavage and urine was collected for 6 h to assess its rate of absorption. Quantitation by gas liquid chromatography revealed that total urinary excretion of PEG 400 increased with aging. 34-week-old rats excreted 34.3% of the administrated dose while 43.6% was excreted in the urine by rats 133 weeks of age. This effect was more pronounced with the higher molecular weight PEG since excretion of the lower molecular weight PEG 282 decreased by 10.5% while PEG 634 excretion increased by 11.4% with aging. The increased permeability of the intestinal tract to higher molecular weight species of PEG may indicate that the intestinal protective barrier to the absorption of potentially harmful environmental substances may be less efficient in aging animals. If similar findings are found in aging humans, they may indicate increased potential for absorption of large antigenic or carcinogenic compounds from the intestinal lumen.


CT as gatekeeper of invasive coronary angiography in patients with suspected CAD.
Cardiac CT has been accepted as a valuable diagnostic tool in today's patient care. However, several other noninvasive, in particular, functional diagnostic tests are available on the menu for the ordering clinician and target more or less the same patient population. These tests come with a cost and financial constraints in the present economic environment will no longer allow its indiscriminate use. The gatekeeper function of a diagnostic testing strategy implies that a test is selected judiciously with the aim of preventing access to invasive yet expensive coronary angiography. On the basis of current knowledge, cardiac CT stands a good chance to claim the position of effective gatekeeper to the cathlab.


Fetal iron deficiency alters the proteome of adult rat hippocampal synaptosomes.
Fetal and neonatal iron deficiency results in cognitive impairments in adulthood despite prompt postnatal iron replenishment. To systematically determine whether abnormal expression and localization of proteins that regulate adult synaptic efficacy are involved, we used a quantitative proteomic approach (isobaric tags for relative and absolute quantitation, iTRAQ) and pathway analysis to identify dysregulated proteins in hippocampal synapses of fetal iron deficiency model. Rat pups were made iron deficient (ID) from gestational day 2 through postnatal day (P) 7 by providing pregnant and nursing dams an ID diet (4 ppm Fe) after which they were rescued with an iron-sufficient diet (200 ppm Fe). This paradigm resulted in a 40% loss of brain iron at P15 with complete recovery by P56. Synaptosomes were prepared from hippocampi of the formerly iron-deficient (FID) and always iron-sufficient controls rats at P65 using a sucrose gradient method. Six replicates per group that underwent iTRAQ labeling and LC-MS/MS analysis for protein identification and comparison elucidated 331 differentially expressed proteins. Western analysis was used to confirm findings for selected proteins in the glutamate receptor signaling pathway, which regulates hippocampal synaptic plasticity, a cellular process critical for learning and memory. Bioinformatics were performed using knowledge-based Interactive Pathway Analysis. FID synaptosomes show altered expression of synaptic proteins-mediated cellular signalings, supporting persistent impacts of fetal iron deficiency on synaptic efficacy, which likely cause the cognitive dysfunction and neurobehavioral abnormalities. Importantly, the findings uncover previously unsuspected pathways, including neuronal nitric oxide synthase signaling, identifying additional mechanisms that may contribute to the long-term biobehavioral deficits.


This time it's personal: the memory benefit of hearing oneself.
The production effect is the memory advantage of saying words aloud over simply reading them silently. It has been hypothesised that this advantage stems from production featuring distinctive information that stands out at study relative to reading silently. MacLeod (2011) (I said, you said: The production effect gets personal. Psychonomic Bulletin & Review, 18, 1197-1202. doi: 10.3758/s13423-011-0168-8 ) found superior memory for reading aloud oneself vs. hearing another person read aloud, which suggests that motor information (speaking), self-referential information (i.e., "I said it"), or both contribute to the production effect. In the present experiment, we dissociated the influence on memory of these two components by including a study condition in which participants heard themselves read words aloud (recorded earlier) - a first for production effect research - along with the more typical study conditions of reading aloud, hearing someone else speak, and reading silently. There was a gradient of memory across these four conditions, with hearing oneself lying between speaking and hearing someone else speak. These results imply that oral production is beneficial because it entails two distinctive components: a motor (speech) act and a unique, self-referential auditory input.


Morphologic evaluation of radiotherapy in cervical carcinoma--a computerized morphometric approach.
Our work analyses the effects of radiotherapy in cervical carcinoma by computerized morphometry techniques that evaluate the morphologic changes in the specimens taken from pre and post-irradiation biopsies of 8 cases. These cases were diagnosed as squamous cell carcinoma, undifferentiated (1 case), moderately (5 cases) and well differentiated (2 cases). For each case, 40 relevant microscopic fields were chosen, reflecting the morphologic aspects before (20 fields) and after irradiation (20 fields). The digitised images of these fields were used for measuring the tumoral and stromal areas by a program we implemented in the Zeiss KS400 environment. The program provides a mean tumoral/stromal area for each case, computed by averaging the results of the 20 measurements performed on the pre and post-irradiation images. In terms of a stereological interpretation, each mean tumoral area expresses the percentage of the tumoral volume and can be used as an index for quantifying the efficiency of the radiotherapy. Such an index allows developing comparative discussions on cases that belong either to the same diagnosis entity, or to different diagnosis entities. These discussions yield the idea that the morphologic classification of a case is not sufficient to accurately predict the efficiency of irradiation, and a systematic approach to the morphometric features, before and after irradiation, may contribute to the refinement of the prediction.


The development of normal feeding and swallowing: Showa University study of the feeding function.
Since the 1980s the Department of Hygiene and Oral Health at the Showa University School of Dentistry has focused its research efforts on the development of feeding function and disorders. In addition, we have treated dysphagic children and dysphagic elderly using our feeding training program approach. The developmental course of the feeding function includes the following steps: 1) Suckle feeding and prefeeding period; 2) Acquiring the ability to swallow with lips closed; 3) Acquiring the ability to take food with lips closed; 4) Acquiring the ability to push mashed food with the tongue and anterior hard palate; 5) Acquiring the ability to perform mastication; 6) Beginning self-feeding; 7) Beginning finger feeding; 8) Beginning using table ware.


Halogenated Antimicrobial Agents to Combat Drug-Resistant Pathogens.
Antimicrobial resistance presents us with a potential global crisis as it undermines the abilities of conventional antibiotics to combat pathogenic microbes. The history of antimicrobial agents is replete with examples of scaffolds containing halogens. In this review, we discuss the impacts of halogen atoms in various antibiotic types and antimicrobial scaffolds and their modes of action, structure-activity relationships, and the contributions of halogen atoms in antimicrobial activity and drug resistance. Other halogenated molecules, including carbohydrates, peptides, lipids, and polymeric complexes, are also reviewed, and the effects of halogenated scaffolds on pharmacokinetics, pharmacodynamics, and factors affecting antimicrobial and antivirulence activities are presented. Furthermore, the potential of halogenation to circumvent antimicrobial resistance and rejuvenate impotent antibiotics is addressed. This review provides an overview of the significance of halogenation, the abilities of halogens to interact in biomolecular settings and enhance pharmacological properties and their potential therapeutic usages in preventing a post-antibiotic era. Significance Statement Antimicrobial resistance and the increasing impotence of antibiotics are critical threats to global health. The roles and importance of halogens atoms in antimicrobial drug scaffolds have been established, but comparatively little is known of their pharmacological impacts on drug resistance and antivirulence activities. This review is the first to extensively evaluate the roles of halogen atoms in various antibiotic classes and pharmacological scaffolds and to provide an overview of their abilities to overcome antimicrobial resistance.


Association of Body Mass Index With Disability in Activities of Daily Living Among Chinese Adults 80 Years of Age or Older.
Body mass index (BMI) shows a U-shaped association with impaired physical functioning among adults; the association is reduced or eliminated with aging. To examine whether BMI is associated with subsequent disability in activities of daily living (ADL) in Chinese adults age 80 years or older. Data were obtained on 16 022 adults age 80 years or older who were able to perform ADL independently at baseline from the Chinese Longitudinal Healthy Longevity Study, a community-based prospective cohort study conducted in 23 provinces of China. The study was initiated in 1998, with follow-up and recruitment of new participants in 2000, 2002, 2005, 2008, 2011, and 2014. Disability in ADL was defined as dependence in eating, toileting, bathing, dressing, indoor activities, and/or continence. Among the 16 022 participants, 45.2% were men and 54.8% were women, with a mean (SD) age of 92.2 (7.2) years and a mean (SD) BMI (calculated as weight in kilograms divided by height in meters squared) of 19.3 (3.8). During 70 606 person-years of follow-up, 8113 participants with disability in ADL were identified. Cox proportional hazards regression models with penalized splines showed that BMI was linearly associated with disability in ADL: each 1-kg/m2 increase in BMI corresponded to a 4.5% decrease in the risk of disability in ADL. In comparison with individuals in the fourth quintile for BMI, the adjusted hazard ratio for disability in ADL was 1.38 (95% CI, 1.29-1.48) in the first quintile, 1.37 (95% CI, 1.28-1.47) in the second quintile, 1.11 (95% CI, 1.04-1.19) in the third quintile, and 0.85 (95% CI, 0.79-0.91) in the fifth quintile (P < .001 for trend). When BMI was categorized by Chinese guidelines, the underweight group (BMI <18.5) showed significantly increased risk of disability in ADL (hazard ratio, 1.34; 95% CI, 1.28-1.41) and the overweight or obese group (BMI ≥24.0) showed significantly decreased risk of disability in ADL (hazard ratio, 0.84; 95% CI, 0.78-0.91) compared with the normal weight group (BMI 18.5 to <24.0) (P < .001 for trend). Higher BMI was associated with a lower risk of disability in ADL among Chinese adults age 80 years or older, which suggests that current recommendations for BMI may need to be revisited. More attention should be paid on underweight, rather than overweight or obesity, for the prevention of disability in ADL after age 80 years.


How are adherent people more likely to think? A meta-analysis of health beliefs and diabetes self-care.
Diabetes is increasingly prevalent, and nonadherence with diabetes treatment regimens is associated with physical and social costs. Psychological predictors of adherence have been investigated in the literature, including cognitive factors. The present meta-analysis was conducted to investigate the association between beliefs related to diabetes and adherence to diabetes regimens. Studies that measured both (a) beliefs, perceptions, or cognitions about diabetes and (b) the relationship between such cognitive factors and blood glucose levels or other adherence behaviors were included. This research focused on adults with any type of diabetes, reaching a final sample of 48 studies. The effect size r was calculated for all types of beliefs and outcomes. The types of beliefs most strongly associated with adherence were self-efficacy, perceiving a positive relationship with physician, and beliefs about the personal consequences of adherence. A few limitations of this meta-analysis are that studies were only retrieved through databases and other sources were not searched, only articles in English were included, and only adult participants were included. People who are more adherent have a higher level of confidence in their ability to follow medical recommendations, expect more meaningful positive consequences for adherence, and perceive a more positive relationship with their health care provider. Educators and clinicians could use cognitive restructuring techniques to facilitate these types of beliefs and perceptions in people with diabetes.


Measuring the invisible: Analysis of the Sustainable Development Goals in relation to populations exposed to drought.
Brazil, together with all the member countries of the United Nations, is in a process of adoption of a group of Sustainable Development Goals, including targets and indicators. This article considers the implications of these goals and their proposed targets, for the Semi-Arid region of Brazil. This region has recurring droughts which may worsen with climate change, further weakening the situation of access of water for human consumption in sufficient quantity and quality, and as a result, the health conditions of the exposed populations. This study identifies the relationship between drought and health, in an effort to measure progress in this region (1,135 municipalities), comparing relevant indicators with the other 4,430 municipalities in Brazil, based on census data from 1991, 2000 and 2010. Important inequalities between the municipalities of this region and the municipalities of the rest of Brazil are identified, and discussed in the context of what is necessary for achieving the Sustainable Development Goals in the Semi-arid Region, principally in relation to the measures for adaptation to achieve universal and equitable access to drinking water.


Point-of-Care Testing for Sexually Transmitted Infections: A Review of Recent Developments.
Sexually transmitted infections (STIs) are among the most common communicable diseases globally and are associated with significant morbidity and mortality worldwide. Point-of-care tests have the potential to revolutionize the prevention and control of STIs by enabling rapid diagnosis and early treatment of infections, thus interrupting transmission and preventing the sequelae of untreated infections. Currently, there are several point-of-care (POC) tests available for the diagnosis of Treponema pallidum, Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis infections, although these tests differ with regard to their performance, turnaround time, and cost. To provide an updated review of the POC tests available and under development for the diagnosis of T pallidum, C trachomatis, N gonorrhoeae, and T vaginalis infections, to discuss the context for which these tests might be used, and to highlight future directions for test development. We reviewed the literature pertaining to the recent development and performance evaluations of POC tests for the diagnosis of syphilis, chlamydia, gonorrhea, and trichomonas. Recently, there has been rapid development of new POC tests for STIs. Although there are inexpensive, rapid, and accurate POC tests available for syphilis, there are few such tests available for the diagnosis of chlamydia, gonorrhea, or trichomonas, and currently none with the ability to detect antimicrobial resistance in N gonorrhoeae. Research evaluating implementation strategies for the currently available tests and the development of additional POC tests that are rapid, accurate, and affordable are urgently needed to address the rising number of STIs worldwide.


Blastocystis spp.: frequency and subtype distribution in iron deficiency anemic versus non-anemic subjects from Egypt.
Many helminthic and protozoal infections have been implicated in iron deficiency anemia (IDA) but few reports have suggested a link between Blastocystis sp. infection and IDA. Herein, we investigated the frequency and the association of the Blastocystis sp. genotype with IDA. Two-hundred and six stool samples were examined for Blastocystis sp. Samples were obtained from 96 cases with a confirmed diagnosis of IDA and 110 matched non-anemic controls. The prevalence of the parasite was significantly higher in the IDA group (54.2%) when compared to controls (17.3%) and was 34.5% in all study subjects. Thus, a relationship between Blastocystis sp. infection and IDA was confirmed. PCR amplification of isolates from cases with IDA and controls using subtype-specific sequenced-tagged site primers found that subtype 3 was the most common (83.3%), followed by subtype 1 (16.7%), and both had similar prevalence in both groups. Therefore, there was no correlation found between the Blastocystis sp. genotype and the occurrence of IDA.


Provitamin A conversion to retinal via the beta,beta-carotene-15,15'-oxygenase (bcox) is essential for pattern formation and differentiation during zebrafish embryogenesis.
The egg yolk of vertebrates contains carotenoids, which account for its characteristic yellow color in some species. Such plant-derived compounds, e.g. beta-carotene, serve as the natural precursors (provitamins) of vitamin A, which is indispensable for chordate development. As egg yolk also contains stored vitamin A, carotenoids have so far been solely discussed as pigments for the coloration of the offspring. Based on our recent molecular identification of the enzyme catalyzing provitamin A conversion to vitamin A, we address a possible role of provitamin A during zebrafish (Danio rerio) development. We cloned the zebrafish gene encoding the vitamin A-forming enzyme, a beta,beta-carotene-15,15'-oxygenase. Analysis of its mRNA expression revealed that it is under complex spatial and temporal control during development. Targeted gene knockdown using the morpholino antisense oligonucleotide technique indicated a vital role of the provitamin A-converting enzyme. Morpholino-injected embryos developed a morphological phenotype that included severe malformation of the eyes, the craniofacial skeleton and pectoral fins, as well as reduced pigmentation. Analyses of gene expression changes in the morphants revealed that distinct retinoic acid-dependent developmental processes are impaired, such as patterning of the hindbrain and differentiation of hindbrain neurons, differentiation of neural crest derivatives (including the craniofacial skeleton), and the establishment of the ventral retina. Our data provide strong evidence that, for several developmental processes, retinoic acid generation depends on local de novo formation of retinal from provitamin A via the carotene oxygenase, revealing an unexpected, essential role for carotenoids in embryonic development.


Clinical efficacy of infliximab plus methotrexate in DMARD naive and DMARD refractory rheumatoid arthritis is associated with decreased synovial expression of TNF alpha and IL18 but not CXCL12.
Tumour necrosis alpha (TNF alpha) blocking agents lead to pronounced clinical effects and reduced synovial infiltrate in rheumatoid arthritis. Laboratory and clinical studies suggest that TNF alpha independent pathways play a role in the disease. To evaluate the immunopathological effects of combination therapy on rheumatoid synovial tissue in order to identify TNF alpha independent mechanisms. 12 rheumatoid patients, including four DMARD (disease modifying antirheumatic drug) naive patients with early disease, were studied for the effect of combination therapy with infliximab and methotrexate on the synovial infiltrate. Biopsies and clinical assessments (DAS28) were carried out before the first and after the third infusion of infliximab. Synovial inflammation was scored semiquantitatively. Co-expression of CD38(+) cells was studied by an immunofluorescent double labelling technique. Marked clinical responses were associated with a global reduction in the synovial infiltrate and expression of cytokines, notably interleukin 18 and TNF alpha, but low grade disease activity persisted. There was no effect on the expression of CXC chemokine ligand (CXCL12), and germinal centre-like structures were still detectable in synovial tissue in two patients after treatment. CD38(+) activated T cells were more resistant to treatment than CD38(+) plasma cells. No differences in clinical response or effects on synovial infiltrate were observed between DMARD refractory and DMARD naive patients. Persistent expression of CXCL12 and incomplete resolution of lymphocytic infiltrates after infliximab plus methotrexate indicates that TNF alpha independent mechanisms are operative in rheumatoid arthritis. This may contribute to low grade disease activity, even in DMARD naive patients with early disease.


Handedness and effective connectivity of the motor system.
Handedness denotes the individual predisposition to consistently use the left or right hand for most types of skilled movements. A putative neurobiological mechanism for handedness consists in hemisphere-specific differences in network dynamics that govern unimanual movements. We, therefore, used functional magnetic resonance imaging and dynamic causal modeling to investigate effective connectivity between key motor areas during fist closures of the dominant or non-dominant hand performed by 18 right- and 18 left-handers. Handedness was assessed employing the Edinburgh-Handedness-Inventory (EHI). The network of interest consisted of key motor regions in both hemispheres including the primary motor cortex (M1), supplementary motor area (SMA), ventral premotor cortex (PMv), motor putamen (Put) and motor cerebellum (Cb). The connectivity analysis revealed that in right-handed subjects movements of the dominant hand were associated with significantly stronger coupling of contralateral (left, i.e., dominant) SMA with ipsilateral SMA, ipsilateral PMv, contralateral motor putamen and contralateral M1 compared to equivalent connections in left-handers. The degree of handedness as indexed by the individual EHI scores also correlated with coupling parameters of these connections. In contrast, we found no differences between right- and left-handers when testing for the effect of movement speed on effective connectivity. In conclusion, the data show that handedness is associated with differences in effective connectivity within the human motor network with a prominent role of SMA in right-handers. Left-handers featured less asymmetry in effective connectivity implying different hemispheric mechanisms underlying hand motor control compared to right-handers.


GluR6/KA2 kainate receptors mediate slow-deactivating currents.
Kainate receptors (KARs) are ionotropic glutamate receptors contributing to EPSCs with a slow-decaying component that is likely essential for synaptic integration. The slow kinetics of KAR-EPSCs markedly contrasts with the fast kinetics reported for recombinant KARs expressed in heterologous systems, for reasons that remain unexplained. Here we have studied the properties of recombinant heteromeric GluR6/KA2 receptors, which compose synaptic KARs. We report that, in response to brief glutamate applications, currents mediated by recombinant GluR6/KA2 receptors, but not GluR6 receptors, decay with a time course similar to KAR-EPSCs. Model simulations suggest that, after brief agonist exposures, GluR6/KA2 currents undergo slow deactivation caused by the stabilization of partially bound open states. We propose, therefore, that the GluR6/KA2 gating features could contribute to the slow KAR-EPSC decay kinetics.


Myocardial insulin resistance, metabolic stress and autophagy in diabetes.
Clinical studies in humans strongly support a link between insulin resistance and non-ischaemic heart failure. The occurrence of a specific insulin-resistant cardiomyopathy, independent of vascular abnormalities, is now recognized. The progression of cardiac pathology linked with insulin resistance is poorly understood. Cardiac insulin resistance is characterized by reduced availability of sarcolemmal Glut-4 transporters and consequent lower glucose uptake. A shift away from glycolysis towards fatty acid oxidation for ATP supply is apparent and is associated with myocardial oxidative stress. Reliance of cardiomyocyte excitation-contraction coupling on glycolytically derived ATP supply potentially renders cardiac function vulnerable to the metabolic remodelling adaptations observed in diabetes development. Findings from Glut-4-knockout mice demonstrate that cardiomyocytes with extreme glucose uptake deficiency exhibit cardiac hypertrophy and marked excitation-contraction coupling abnormalities characterized by reduced sarcolemmal Ca(2+) influx and sarcoplasmic reticulum Ca(2+) uptake. The 'milder' phenotype fructose-fed mouse model of type 2 diabetes does not show evidence of cardiac hypertrophy, but cardiomyocyte loss linked with autophagic activation is evident. Fructose feeding induces a marked reduction in intracellular Ca(2+) availability with myofilament adaptation to preserve contractile function in this setting. The cardiac metabolic adaptations of two load-independent models of diabetes, namely the Glut-4-deficient mouse and the fructose-fed mouse are contrasted. The role of autophagy in diabetic cardiopathology is evaluated and anomalies of type 1 versus type 2 diabetic autophagic responses are highlighted.


Monte Carlo simulation of light fluence in tissue in a cylindrical diffusing fibre geometry.
The propagation of light emitted by a linear light diffuser in a cylindrical hollow organ was investigated by means of the Monte Carlo (MC) method. The height and radius of the cavity, scattering (mu(s)) (or reduced scattering, mu'(s)) and absorption (mu(a)) coefficients, anisotropy (g), and refractive indices of the media involved (n1, n2) are required as input data by the MC code, as are characteristics of the light diffuser (length, delivered power and emission profile). Results of our MC model were tested by measuring the light fluence rate in a tissue-simulating phantom (mu(a) = 0.5 cm(-1), mu(s) = 23 cm(-1) and g = 0.75) irradiated at 633 nm with a cylindrical diffuser. Since geometric and optical parameters determine the behaviour of light propagation in tissue, MC simulations with different sets of input parameters were carried out to provide qualitative as well as quantitative data useful in planning photodynamic therapy. Data are reported on light penetration and fluence rate build-up at mu(a) and mu'(s) values ranging between 0.1 and 5 cm(-1) and 2.5 and 50 cm(-1), respectively. Furthermore, results suggest that a shift and spread could occur in the isofluence curves along the symmetry axis, which depend on the diameter of the treated lumen as well as on the emission profile of the light diffuser. Using our data it is possible to estimate how inaccuracy in knowledge of the optical coefficients can affect (i.e. usually by increasing) the light dose scheduled at a certain depth into tissue.


Aryl hydrocarbon receptor-activating polychlorinated biphenyls and their hydroxylated metabolites induce cell proliferation in contact-inhibited rat liver epithelial cells.
Polychlorinated biphenyls (PCBs) exhibit tumor-promoting effects in experimental animals. We investigated effects of six model PCB congeners and hydroxylated PCB metabolites on proliferation of contact-inhibited rat liver epithelial WB-F344 cells. The 'dioxin-like' PCB congeners, PCB 126, PCB 105, and 4'-OH-PCB 79, a metabolite of the planar PCB 77 congener, induced cell proliferation in a concentration-dependent manner. In contrast, the 'non-dioxin-like' compounds that are not aryl hydrocarbon receptor (AhR) agonists, PCB 47, PCB 153, and 4-OH-PCB 187, an abundant noncoplanar PCB metabolite, had no effect on cell proliferation at concentrations up to 10 muM. The concentrations of dioxin-like PCBs leading to cell proliferation corresponded with the levels inducing the expression of cytochrome P450 1A1 mRNA, suggesting that the release from contact inhibition was associated with AhR activation. The effects of PCB 126 and PCB 153 on expression of proteins controlling G0/G1-S-phase transition and S-phase progression were compared. Only PCB 126 was found to upregulate cyclin A and D2 protein levels, and to increase both total cyclin-dependent kinase 2 (cdk2) and cyclin A/cdk2 complex activities. Despite the observed upregulation of cyclin D2, no increase in cdk4 activity was observed. The expression of cdk inhibitor p27Kip1 was not affected by either PCB 126 or PCB 153. These results suggest that dioxin-like PCBs can induce cell proliferation of contact-inhibited rat liver epithelial cells by increasing cyclin A protein levels, a process that then leads to upregulation of cyclin A/cdk2 activity and initiation of DNA replication. This mechanism could be involved in tumor-promoting effects of dioxin-like PCBs.


Comprehensive allelotype study of hepatocellular carcinoma: potential differences in pathways to hepatocellular carcinoma between hepatitis B virus-positive and -negative tumors.
To examine the role of the loss of heterozygosity (LOH) in hepatitis-related carcinogenesis, we performed a genome-wide scan of LOH in 44 tumors of hepatocellular carcinoma (HCC) using 216 microsatellite markers throughout all human chromosomes. A high frequency of LOH (>30% of informative cases) was observed at 33 loci on chromosome arms 4q, 6q, 8p, 8q, 9p, 9q, 13q, 16p, 16q, 17p, and 19p. LOH on 19p has not yet been reported, and that appears to be a new candidate in the search for tumor suppressor genes. High rates of LOH are correlated with hepatitis B virus (HBV) positivity, poorly differentiated tumors, vascular invasion, and intrahepatic metastasis (P <.0001). LOH on 13q and 16q occurred more frequently in HBV(+) patients (P <.0001), and LOH on 6q occurred more frequently in virus-negative patients (P <.001). The frequency of LOH on 4q and 13q was significantly lower in well-differentiated tumors than in moderately and poorly differentiated tumors (P <.01). In contrast, LOH on 6q was frequently detected in well-differentiated tumors compared with other histological subclasses (P <.001). Our results suggest that LOH on 6q may play an important role in the early stage of hepatocarcinogenesis in virus-negative patients, but different mechanisms might underlie the initial step to carcinogenesis in HBV(+) patients. LOH on 13q and 16q may play an essential role in the progression of HBV(+) tumors. Further studies of fine deletion mapping on chromosomes 13q and 16q are required to define the genomic segments on which putative tumor suppressor genes responsible for HBV(+) tumors exist.


Expression profiling after retinal detachment and reattachment: a possible role for aquaporin-0.
Retinal detachment (RD) is associated with acute visual loss caused by anatomic displacement of the photoreceptors and with chronic visual loss/disturbance caused by retinal remodeling and photoreceptor cell death, which may occur even after successful reattachment. The P2Y(2) receptor agonist INS37217 improves the rate of retinal reattachment in animal models of induced RD, and has been shown to also significantly enhance the rate of ERG recovery in a mouse model of RD. The identification of genes modulated by INS37217 may allow further drug discovery for treating RD and edema. To identify genes involved in RD and subsequent reattachment, a retinal microarray screen was performed using a mouse model of RD in the presence or absence of INS37217. Ninety-two genes were identified as differentially expressed across three time points, most of which were upregulated in the presence of this agonist. Furthermore, it was shown that RD alters the expression of aquaporin-0 (AQP-0), and this modulation is prevented by treatment with INS37217. The presence of AQP-0 in retinal bipolar cells was also demonstrated, whereas it was previously thought to be specific to the lens. Mice lacking functional alleles of AQP-0 had a phototransduction deficit as assessed by electroretinography; however, their photoreceptor structure was normal, indicative of a problem with signal transmission between neurons. This study establishes the genes involved in RD and reattachment, and also demonstrates for the first time a physiologically significant role for AQP-0 in retinal function.


Chondroitin sulfate expression predicts poor outcome in breast cancer.
Experimental studies have established that the sulfated glycosaminoglycans heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and growth factors that drive the malignant cell phenotype and the remodelling of the surrounding tumor stroma. However, the clinical relevance of these studies remains ill-defined. The present study investigates the significance of chondroitin sulfate expression in malignant cells and the stroma, respectively, of tumors from two independent cohorts of breast cancer patients (cohort I: 144 patients, 130 evaluable samples; cohort II: 498 patients, 469 evaluable samples; ER-positive patients ~86% in both cohorts). Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the relationship between chondroitin sulfate and recurrence-free and overall survival. High chondroitin sulfate expression in malignant cells was shown to predict shorter recurrence-free survival (P=0.007, cohort I; P=0.024, cohort II) and overall survival (cohort I: P=0.044; cohort II: P<0.001) in both cohorts. In multivariate analysis, high chondroitin sulfate in malignant cells was shown to be an independent, predictive factor of poor overall survival (cohort I: hazard ratio 2.28: 95% confidence interval 1.08-4.81, P=0.031; cohort II: hazard ratio 1.71: 95% confidence interval 1.23-2.38, P=0.001). However, chondroitin sulfate in the stroma showed no correlation with known markers of tumor aggressiveness or with clinical outcome in either cohort. Our data suggest that high chondroitin sulfate expression in malignant cells is associated with an adverse outcome in patients with primary breast cancer, supporting the idea of a functional and potentially targetable role of chondroitin sulfate in tumor disease.


Headache relief 10 years after cervical disc arthroplasty: multicenter randomized clinical trial post hoc analysis.
Headache relief after anterior cervical spine surgery has been reported. No study, however, has followed patients out to 10 years to assess the durability of headache improvement. The authors analyzed a group of patients with a 10-year follow-up after one- or two-level cervical disc arthroplasty (CDA) from an FDA investigational device exemption (IDE) study. The authors performed a post hoc analysis of 189 patients treated with CDA from the 9 highest enrolling sites in a prospective multicenter randomized US FDA IDE clinical trial. Patients had one- or two-level CDA at contiguous levels from C3 to C7 using the Mobi-C device. The authors evaluated headache scores from the headache section of the Neck Disability Index (NDI), along with associated demographic variables (age, sex, race, ethnicity, and BMI). Preoperative and 10-year postoperative headache scores were analyzed. Primary analysis was conducted via the Wilcoxon rank-sum test, followed by univariate and multivariable logistic regression. After accounting for age, BMI, race, ethnicity, and sex, there was sustained headache improvement 10 years after CDA (p = 0.04). Preoperatively, the median NDI score was 3.00 (IQR 1.00-4.00) and after 10 years it was 1.00 (IQR 0.00-2.00), with a decrease in the NDI score by 1.00 point (95% CI 0.00-2.00, p = 0.04). For one-level CDA, the median NDI score was 3.00 (IQR 1.00-4.00) preoperatively but 1.00 (IQR 0.00-2.00) at 10 years, with an estimated reduction in the NDI score of 1 point (95% CI 1.00-2.00, p < 0.0001). For two-level CDA, the median NDI score was 3.00 (IQR 1.75-4.00) preoperatively and 1.00 (IQR 0.00-2.00) at 10 years, with an estimated reduction in the NDI score of 1 point (95% CI 1.00-2.00, p < 0.0001). Headache relief provided by cervical CDA, for symptomatic C3-7 cervical spondylosis, was sustained even 10 years after surgery. There was no difference in headache improvement between the one- and two-level CDA groups, or among BMI, sex, race, and ethnicity strata.


Determining the sagittal dimensions of the canal of the cervical spine. The reliability of ratios of anatomical measurements.
The ratio of the sagittal diameter of the cervical canal to the corresponding diameter of the vertebral body has been described as a reliable means for assessing stenosis of the canal and detecting those at risk of cervical neuropraxia. The use of ratio techniques has the advantage of avoiding variation in magnification when direct measurements are made from plain radiographs. We examined the reliability of this method using plain lateral radiographs of unknown magnification and CT scans. We also assessed other possible ratios of anatomical measurements as a guide to the diameter of the canal. Our findings showed a poor correlation between the true diameter of the canal and the ratio of its sagittal diameter to that of the vertebral body. No other more reliable ratio was identified. The variability in anatomical morphology means that the use of ratios from anatomical measurements within the cervical spine is not reliable in determining the true diameter of the cervical canal.


Syncope at SARS-CoV-2 onset.
We describe clinical and laboratory findings in 35 patients tested positive for SARS-CoV-2 by reverse transcriptase-polymerase chain reaction on nasopharyngeal swab experiencing one or multiple syncope at disease onset. Clinical neurologic and cardiologic examination, and electrocardiographic findings were normal. Chest computed tomography showed findings consistent with interstitial pneumonia. Arterial blood gas analysis showed low pO2, pCO2, and ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) indicating hypocapnic hypoxemia. Patients who presented with syncope showed significantly lower heart rate as compared to 68 SARS-CoV-2 positive that did not. Such poorer than expected compensatory heart rate increase may have led to syncope based on individual susceptibility. We speculate that SARS-CoV-2 could have caused angiotensin-converting enzyme-2 (ACE2) receptor internalization in the nucleus of the solitary tract and other midbrain nuclei, impairing baroreflex and chemoreceptor response, and inhibiting the compensatory tachycardia during acute hypocapnic hypoxemia.


Early structural degeneration of Mitroflow aortic valve: another issue in addition to the mismatch?
We reported two cases of early structural valve degeneration (SVD) with Mitroflow prosthesis in aortic position in patients above the age of 65 years. Microscopic aspects have been analysed to investigate the intrinsic mechanism of SVD. New techniques to improve the structure and the preservation of this prosthesis are needed in order to reduce potential dangerous early complications.


Mechanism of capsaicin-induced relaxation in equine tracheal smooth muscle.
The effects of capsaicin and neuropeptides were examined in equine tracheal smooth muscle (TSM). Neither capsaicin nor substance P (SP) contracted TSM. Capsaicin (100 microM) elicited relaxation in TSM contracted with methacholine. This relaxation was not mimicked by SP or calcitonin gene-related peptide (CGRP). Relaxation was not attenuated by removal of the epithelium or by pretreatment of tissue with meclofenamate or the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine. Previous exposure of TSM to capsaicin did not eliminate the relaxation responses to subsequent capsaicin. Although vasoactive intestinal peptide (VIP) elicited marked relaxation that was attenuated by alpha-chymotrypsin, alpha-chymotrypsin did not affect the capsaicin-induced relaxation. Capsaicin-induced relaxation was abolished by charybdotoxin, a blocker of large-conductance Ca(2+)-activated K+ channels. These results indicate that capsaicin-induced equine TSM relaxation is not mediated either by neuropeptides such as SP or CGRP released from capsaicin-sensitive sensory nerves or by prostanoids, NO, or VIP. Relaxation is due to the effect of capsaicin on large-conductance Ca(2+)-activated K+ channels. The peptidergic nerves play no important role in the regulation of TSM tone in horse airways.


Testing for salmonella spp. In released parrots, wild parrots, and domestic fowl in lowland peru.
Wild animal populations face threats from pathogens from both intentionally released captive animals and domestic animals that accompany human settlements. From December 2004 through August 2005, we studied free living macaws and parrots in the Tambopata National Reserve in the Peruvian Amazon and semicaptive domestic fowl in human settlements adjacent to the reserve. In 1992-1993, large macaws (Aras spp.) that were serologically positive for Salmonella Pullorum were released into this reserve, which hosts dense populations of free-living parrots and macaws. We collected cloacal swabs from 64 birds and cultured for Salmonella spp. via standard laboratory methods. All 35 psittacines tested were culture negative for Salmonella spp., while 31% of 29 domestic fowl were culture positive. Our findings suggest that the domestic fowl that accompany human settlement in this region carry and shed Salmonella spp. that could threaten wild bird populations in and around the reserve.


Hemodynamic parameters predict adverse outcomes following biventricular conversion with single-ventricle palliation takedown.
Patients with a borderline left ventricular hypoplasia in the hypoplastic left heart syndrome variant or an unbalanced atrioventricular canal who undergo initial single-ventricle palliation may be candidates for biventricular (BiV) conversion following left ventricle (LV) recruitment procedures. We investigated associations among preoperative parameters and postoperative outcomes in patients undergoing BiV conversion. We performed a retrospective review of patients who underwent BiV conversion to determine variables associated with clinical outcomes. Predictor variables included cardiac diagnosis, age and weight, LV dimension, LV end diastolic volume, LV mass, preoperative LV end diastolic pressure (LVEDP), and preoperative left atrial pressure. Primary outcome was a composite of death, heart transplant, or BiV takedown. Of 51 patients, 11 experienced primary outcome (22%). Patients with hypoplastic left heart syndrome variant were more likely to experience primary outcome than those with an unbalanced atrioventricular canal (30% vs 6%; P = .03). Receiver operating characteristic analysis demonstrated that preoperative LVEDP had good predictive accuracy in classifying patients with and without the primary outcome (area under the curve, 0.757; 95% confidence interval, 0.594-0.919; P = .012). The Youden J-index indicated a cutoff of LVEDP ≥ 13 mm Hg as optimal for predicting the primary outcome. Multivariable Cox regression demonstrated that LVEDP ≥ 13 mm Hg (adjusted hazard ratio, 4.00; P = .037) and postoperative right ventricle pressure > 3/4 (adjusted hazard ratio, 21.75; P < .001) were significantly associated with primary outcome, independent of age, weight, and diagnosis. Elevated preoperative LVEDP is a risk factor for suboptimal postoperative hemodynamic parameters and adverse outcome following BiV conversion from single-ventricle palliation.


Sex behavior among high school students in Sweden: improvement in contraceptive use over time.
To investigate sexual behavior and attitudes toward sexuality among first-year high school students in Sweden in 1999 and to compare the sexual behavior with that reported from similar studies in 1979 and 1989. In Spring 1999, a questionnaire with 47 questions mainly of multiple-choice nature was administered to a random sample of 20 classes in senior high school in two medium-sized cities in Sweden. The median age of the students was 16 years. Differences in sexual behavior and attitudes were evaluated with the Chi-square and Student's t-test. Almost half of the students (46%) had had intercourse, showing that the age of coitarche had not decreased during the past two decades. The median age at intercourse of those who had had intercourse was 15 years in both genders. More students in practical (vocational-technical) programs (60%) than in theoretical (college preparatory) ones (37%) had had sexual intercourse. More teenagers in theoretical (90%) than in practical programs (64%) had used contraceptives at their first intercourse, an increase from 65% in 1979 to 76% in 1999. One-fourth of the teenagers were under the influence of alcohol at the first intercourse, a decrease, compared with 1979. Contraceptive use at coitarche has increased and alcohol use decreased over the 20-year-period. The tendency noted 10 years ago that students attending practical programs put themselves at more health risk than students in theoretical programs continues. This fact should be considered when planning for counseling and sex education.


Notes From the Field: Applying the Consolidated Framework for Implementation Research in a Qualitative Evaluation of Implementation of the Queensland Aboriginal and Torres Strait Islander Brief Intervention Training Program.
This paper describes the applicability of the Consolidated Framework for Implementation Research (CFIR) to the qualitative evaluation of the implementation of the Queensland Aboriginal and Torres Strait Islander Brief Intervention Training Program, the B.strong Program. Interviews were conducted with 20 B.strong Program trainees and four health service managers from eight purposively sampled Indigenous primary health care services in Queensland to collect their perceptions of the B.strong Program implementation. The 26 constructs of the CFIR were used to guide data collection and analysis. Additional constructs were developed for two program implementation aspects, "quality improvement" and "cultural suitability." Findings are presented from the application of the CFIR to the evaluation of the implementation of a brief intervention training program in the Australian Indigenous context. While demonstrating the applicability of the CFIR in this evaluation, this study also highlights that it may require modification, to ensure identification of the different contextual factors that influence program implementation.


In vitro protein fractionation methods for ruminant feeds.
Estimating protein fractions and their degradation rate are vital to ensure optimum protein supply and degradation in the digestive system of ruminants. This study investigated the possibility of using the ANKOM gas production system and preserved rumen fluid to estimate the protein fractions and in vitro degradability of protein-rich feeds. Three in vitro methods: (1) gas production method (2) Cornell Net Carbohydrate and Protein System (CNCPS), and (3) the unavailable nitrogen assay of Ross (uNRoss) were used to quantify protein fractions of four feeds (lupin meal, vetch grain, Desmanthus hay, and soybean meal). Rumen fluid mixed with 5% dimethyl sulfoxide and frozen at -20 °C was also compared against fresh rumen fluid in the gas production and uNRoss methods. All three methods ranked the feeds identically in the proportions of available (degradable or 'a + b') protein fractions as vetch grain, soybean meal, lupin meal, and Desmanthus hay in decreasing order. The use of fresh rumen fluid produced greater available protein fractions than preserved rumen fluid in all feeds. However, there was no difference between total gas production from lupin meal and vetch grain fermented for 16 h in either rumen fluid source. The in vitro degradable CP (IVDP) was higher for vetch grain (46 and 70%) at the 4th and 8th hours of incubation than other feeds, whereas soybean meal (85%) exceeded the other feeds after the 16th hour of incubation (P < 0.001). The greatest ammonia-N concentration was from soybean meal (1.27 mg/g) and lupin meal (0.87 mg/g) fermented for four hours using fresh rumen fluid. The proportion of fraction 'b' for soybean (82.1% CP) and lupin meals (39.4% CP) from the CNCPS method were not different (P = 0.001) from the fraction 'b' estimation of the gas production method for the same feeds (r = 0.99). Regardless of the methods, a greater water-soluble protein fraction was found from vetch grain (39.6-46.6% CP), and the proportion of fraction 'c' or unavailable protein in Desmanthus hay (39.1-41.5% CP) exceeded other substrates (P < 0.001). The strong positive correlation between fractions across different methods and identical ranking of feeds suggests the possibility of using ANKOM gas production apparatus for protein fractionation.


Differential inhibition of nerve growth factor and epidermal growth factor effects on the PC12 pheochromocytoma line.
Tests have been made of the action of the methyltransferase inhibitors 5'-S-methyl adenosine, 5'-S-(2-methyl-propyl)-adenosine, and 3-deaza-adenosine +/- L-homocysteine thiolactone, on nerve growth factor (NGF)-dependent events in the rat pheochromocytoma line PC12. Each of these agents inhibited NGF-dependent neurite outgrowth at concentrations of the order of millimolar. Slow initiation of neurite outgrowth over several days and more rapid regeneration of neurites (congruent to 1 d) were blocked, as was the priming mechanism necessary for genesis of neurites. The inhibitions were reversible in that PC12 cells maintained for several days in the presence of inhibitors grew neurites normally after washout of these agents. Other NGF-dependent responses of the PC12 line (i.e., induction of ornithine decarboxylase activity [over 4 h], enhancement of tyrosine hydroxylase phosphorylation [over 1 h], and rapid changes in cell surface morphology [30 s onward]) were inhibited by each of the agents. In contrast, corresponding epidermal growth factor-dependent responses in ornithine decarboxylase activity, phosphorylation, and cell surface morphology were not blocked, but instead either unaffected or enhanced, by the methylation inhibitors. These inhibitors did not act by blockade of binding of NGF to high- or low-affinity cell surface receptors, though they partially inhibited internalization of [125I]NGF. The inhibition of rapidly-induced NGF-dependent events and the differential inhibition of responses to NGF and epidermal growth factor imply that the methyltransferase inhibitors specifically block one of the first steps in the mechanistic pathway for NGF.


ROS production in brown adipose tissue mitochondria: the question of UCP1-dependence.
Whether active UCP1 can reduce ROS production in brown-fat mitochondria is presently not settled. The issue is of principal significance, as it can be seen as a proof- or disproof-of-principle concerning the ability of any protein to diminish ROS production through membrane depolarization. We therefore undertook a comprehensive investigation of the significance of UCP1 for ROS production, by comparing the ROS production in brown-fat mitochondria isolated from wildtype mice (that display membrane depolarization) or from UCP1(-/-) mice (with a high membrane potential). We tested the significance of UCP1 for glycerol-3-phosphate-supported ROS production by three methods (fluorescent dihydroethidium and the ESR probe PHH for superoxide, and fluorescent Amplex Red for hydrogen peroxide), and followed ROS production also with succinate, acyl-CoA or pyruvate as substrate. We studied the effects of the reverse electron flow inhibitor rotenone, the UCP1 activity inhibitor GDP, and the uncoupler FCCP. We also examined the effect of a physiologically induced increase in UCP1 amount. We noted GDP effects that were not UCP1-related. We conclude that only ROS production supported by exogenously added succinate was affected by the presence of active UCP1; ROS production supported by any other tested substrate (including endogenously generated succinate) was unaffected. This conclusion indicates that UCP1 is not involved in control of ROS production in brown-fat mitochondria. Extrapolation of these data to other tissues would imply that membrane depolarization may not necessarily decrease physiologically relevant ROS production. This article is a part of a Special Issue entitled: 18th European Bioenergetics Conference (Biochim. Biophys. Acta, Volume 1837, Issue 7, July 2014).


Comparison of epicardial fat volume by computed tomography in black versus white patients with acute chest pain.
Disparities in the risk of coronary artery disease (CAD) between races may be influenced by differences in the thoracic adipose tissue. We compared computed tomography (CT)-derived volumes of epicardial adipose tissue (EAT), mediastinal adipose tissue (MAT), and pericoronary fat thickness (PFT) and correlations with CAD between black and white patients. This institutional review board-approved Health Insurance Portability and Accountability Act-compliant study included 372 age- and gender-matched black versus white patients (186 black, 54 ± 11 years, 50% men; 186 white, 54 ± 11 years, 50% men) who underwent CT for chest pain evaluation. EAT, MAT, and PFT were measured. The amount of coronary calcium was quantified as calcium score. CAD was defined as ≥50% coronary artery narrowing. EAT and MAT volumes were significantly lower in black than white patients (59 [twenty-fifth to seventy-fifth percentile 39 to 84] vs 97 [67 to 132] cm(3) and 44 [27 to 77] vs 87 [52 to 157] cm(3), for both p <0.001). Mean PFT in black patients was slightly lower than white patients (17.2 ± 3.2 vs 18.1 ± 3.4 mm, p <0.01). The relation between race and extent of adipose tissue remained significant after adjustment for cardiovascular risk factors. Significant correlations were observed between EAT and MAT volumes and calcium score in black and white patients (r = 0.19 to 0.26, p <0.01). For both races, the level of thoracic fat measurements was higher in present versus absent coronary calcification. A greater amount of thoracic fat was found with obstructive CAD only in white patients. In conclusion, CT-derived measurements of thoracic fat differ between symptomatic black and white patients, suggesting a differential relation between thoracic adipose tissue and CAD pathophysiology by race.


Actual and potential transpiration and carbon assimilation in an irrigated poplar plantation.
We examined the tradeoffs between stand-level water use and carbon uptake that result when biomass production of trees in plantations is maximized by removing nutrient and water limitations. A Populus trichocarpa Torr. x P. deltoides Bartr. & Marsh. plantation was irrigated and received frequent additions of nutrients to optimize biomass production. Sap flux density was measured continuously over four of the six growing-season months, supplemented with periodic measurements of leaf gas exchange and water potential. Measurements of tree diameter and height were used to estimate leaf area and biomass production based on allometric relationships. Sap flux was converted to canopy conductance and analyzed with an empirical model to isolate the effects of water limitation. Actual and soil-water-unlimited potential CO(2) uptakes were estimated with a canopy conductance constrained carbon assimilation (4C-A) scheme, which couples actual or potential canopy conductance with vertical gradients of light distribution, leaf-level conductance, maximum Rubisco capacity and maximum electron transport. Net primary production (NPP) was about 43% of gross primary production (GPP); when estimated for individual trees, this ratio was independent of tree size. Based on the NPP/GPP ratio, we found that current irrigation reduced growth by about 18% compared with growth with no water limitation. To achieve maximum growth, however, would require 70% more water for transpiration, and would reduce water-use efficiency by 27%, from 1.57 to 1.15 g stem wood C kg(-1) water. Given the economic and social values of water, plantation managers appear to have optimized water use.


Effectiveness of acupuncture on pregnancy success rates for women undergoing in vitro fertilization: A randomized controlled trial.
To investigate the effect of acupuncture on pregnancy success rates applied before and after embryo transfer (ET) among women undergoing in vitro fertilization (IVF). In this randomized controlled trial, 72 infertile women undergoing IVF were randomized to acupuncture (AG; n = 36) and control group (CG; n = 36). Three sessions of acupuncture were applied to AG, the first was one week before ET, the second was 30 min before ET, and the third was 30 min after ET. CG received no acupuncture. The primary outcome was pregnancy success rate (Beta-HCG level, clinical pregnancy, ongoing pregnancy, live birth). Secondary outcome was anxiety level (STAI-1 state anxiety scale). Beta-HCG levels were assessed for conception 12 days after ET. Additionally, STAI-1 state anxiety scale was administered 30 min before and after ET to measure anxiety levels in both groups. The mean age was 30.9 ± 3.7 years. Positive Beta HCG was detected in 63.9% (n = 23) of the AG and 33.3% (n = 12) of CG (p = 0.009). Clinical pregnancy, ongoing pregnancy, and live birth rates were higher in AG (p < 0.05). There was no difference between the groups concerning anxiety scores before ET (p > 0.05). The mean STAI-1 score was decreasing from 57.3 ± 9.8 to 28.8 ± 3.3 in AG, while it was decreasing from 57.0 ± 8.0 to 41,1 ± 6,8 in CG after ET (p < 0.000). It was observed that three sessions of acupuncture before and after ET significantly increased the pregnancy rates in women with unexplained infertility. It was also found that acupuncture significantly reduced anxiety levels that occurred before ET.


Localization of tumor necrosis factor alpha in synovial tissues and at the cartilage-pannus junction in patients with rheumatoid arthritis.
Using immunoaffinity-purified polyclonal anti-human recombinant tumor necrosis factor alpha (TNF alpha) F(ab')2 fragments and immunohistochemical techniques, the cells that make TNF alpha were localized in the inflamed synovial tissue of patients with rheumatoid arthritis (RA) and osteoarthritis (OA). Anti-TNF alpha antibody-stained cells were demonstrated in 9 of 11 RA and 2 of 4 OA but none of 5 normal synovial membranes examined. In RA, 26-64% of the lining layer cells were positive for TNF alpha. In the interaggregate area, 10-30% of the cells contained TNF alpha, often in a perivascular distribution, and up to 19% of the cells in lymphoid aggregates stained for TNF alpha. Some endothelial cells also stained with these antibodies. In OA tissues, the TNF alpha-containing cells were found predominantly in the deeper layer. Cells containing TNF alpha were also found at the cartilage-pannus junction in all 4 RA specimens examined. Double immunofluorescence analysis demonstrated that most TNF alpha-secreting cells in the RA synovial membrane expressed the monocyte/macrophage marker antigens CD11b and CD14, and a few expressed the T cell marker CD3. Our findings provide histologic evidence that TNF alpha is locally produced in the lining and deeper layers of the synovium by cells of the monocyte/macrophage lineage, supporting its role in inflammation. Further, our findings demonstrate that TNF alpha is produced by cells at the cartilage-pannus junction, which could affect chondrocyte metabolism, leading to the cartilage degradation in RA.


[The surgical treatment of fecal incontinence in children].
Based on his experience with treatment of 112 children the author considers that severe and various disturbances of the rectum abturative apparatus function arising from surgical interventions in the anorectal area require the differentiated approach to choice of the method of surgical correction of the incontinence. The transplantation of the denervated muscle, transplantation of the vascular-nervous thoraco-dorsal flap, a lavsan band were used to make a pubo-rectal loop, plasty of the outer and inner sphincters being performed mainly with local tissues.


Sonographic appearance of ductal carcinoma in situ diagnosed with ultrasonographically guided large core needle biopsy: correlation with mammographic and pathologic findings.
The purpose of this study was to evaluate sonographic features of ductal carcinoma in situ diagnosed percutaneously at ultrasonographically guided large core needle biopsy. Of 619 biopsies, 203 breast carcinomas were diagnosed, of which nine were pure ductal carcinoma in situ. All ductal carcinoma in situ lesions appeared sonographically as hypoechoic masses without a pseudocapsule. Grade 1 lesions (n = 2; mean size, 9.5 mm), grade 2 lesions (n = 4; mean size, 18 mm) and grade 3 lesions (n = 3; mean size, 32 mm) had means of 0, 1, and 5 malignant sonographic features, respectively. Ductal carcinoma in situ appeared mammographically as a mass, with two of four grade 2 lesions and all grade 3 lesions demonstrating suspicious microcalcifications. One grade 3 ductal carcinoma in situ was spiculated. In conclusion, ductal carcinoma in situ lesions tended to show more malignant mammographic and sonographic features as histologic grade and size increased.


The effects of diazepam on human self-aggressive behavior.
Diazepam, a benzodiazepine with a relatively rapid onset of clinical effects, has been associated with suicide and other self-aggressive acts. The evidence for this association, however, comes exclusively from retrospective non-experimental studies. Although suggestive, the results of these studies do not support a cause-and-effect relationship between benzodiazepine consumption and self-aggressive behavior. To experimentally examine the effect of diazepam on human self-aggressive behavior under controlled laboratory conditions. Forty-six healthy men and women were randomly assigned to receive placebo, or 5 mg or 10 mg diazepam in a double-blind, between-groups design. Participants were then provided the opportunity to self-administer electric shocks during a competitive reaction-time task (the self-aggression paradigm, SAP). Self-aggression was defined by the intensity of shock chosen. Diazepam (10 mg) was associated with higher average shock self-administered than placebo. Subjects receiving 10 mg diazepam were also more likely to attempt to self-administer a shock that they were led to believe was "severe" and painful. Sedation effects were found, but diazepam consumption did not impair memory, attention, concentration, pain threshold, or reaction-time performance. Clinically relevant diazepam doses may be associated with self-aggressive behaviors at levels that do not significantly impair basic cognitive processes or psychomotor performance.


[Two-dimensional model of a double-well potential: proton transfer when a hydrogen bond is deformed].
The potential energy cross-section profile along a hydrogen bond may contain two minima in certain conditions; it is so-called a double well potential. The H-bond double well potential is essential for proton transfer along this hydrogen bond. We have considered the two-dimensional model of such double well potential in harmonic approximation, and we have also investigated the proton tunneling in it. In real environments thermal motion of atoms or conformational changes may cause reorientation and relative shift of molecule fragment forming the hydrogen bond and, as a result, the hydrogen bond isdeformed. This deformation is liable to change the double well potential form and, hence, the probability of the proton tunneling is changed too. As it is shown the characteristic time of proton tunneling is essentially increased by even small relative shift of heavy atoms forming the H-bond and also rotational displacement of covalent bond generated by one of heavy atoms and the proton (hydrogen atom). However, it is also shown, at the certain geometry of the H-bond deformation the opposite effect occurred, i.e., the characteristic time is not increased and even decreased. Notice that such its behavior arises from two-dimensionality of potential wells; this and other properties of our model are discussed in detail.


Reduction in cardiac contractility during upper respiratory stimulation with cigarette smoke.
Lightly anesthetized rabbits were instrumented to measure arterial pressure, peak left ventricular pressure (LVP) and its first derivative (LV dP/dt), electrocardiogram (ECG), heart rate (HR), and respiratory movements. Through a midtracheal incision two cannulas were inserted, one to allow spontaneous respiration of room air and the other to permit perfusion of the upper airways with unfiltered cigarette smoke. When 50 ml of smoke were passed out of the nostrils, we observed apnea (33.3 s), increases in mean arterial pressure (MAP) (31.9 mmHg) and LVP (38.3 mmHg), as well as decreases in HR (-125 beats/min) and LV dP/dtmax (-45%). After bilateral vagotomy, the responses of MAP and LVP to smoke exposure were not different from those in intact animals. The decrease in LV dP/dtmax (-27%) was, however, significantly less than in intact animals. Also, HR responses were not as pronounced after vagotomy. beta-Blockade after vagotomy abolished the LV dP/dt response to smoke, and the HR response was nearly abolished. MAP and LVP still underwent significant increases due to the smoke. After total sinoaortic denervation plus vagotomy in a second group of animals, a significant fall in LV dP/dtmax (-25%) persisted, and a small HR decrease was observed even when MAP was not allowed to change significantly. The results demonstrate that sympathetic outflow to the heart decreases while there is a net increase in sympathetic activity to the peripheral vasculature. The dramatic vagal bradycardia observed contributes part of the change in LV dP/dtmax. Reflexes originating in the circulation (vagal or sinoaortic) may also contribute to the fall in LV dP/dtmax, but a significant response persists in their absence.