Spatial Computing for preoperative planning and postoperative evaluation of single-position lateral approaches in spinal revision surgery.
Spatial computing (SC) in a surgical context offers reconstructed interactive four-dimensional models of radiological imaging. Preoperative and postoperative assessment with SC can offer more insight into personalized surgical approaches. Spine surgery has benefitted from the use of perioperative SC assessment. Herein, we describe the use of SC to perform a perioperative assessment of a revision spinal deformity surgery. A 79-year-old wheelchair-bound male presented to the neurosurgery clinic with a history of chronic lumbar pain associated with bilateral lower extremity weakness. His surgical history is significant for an L2-L5 lumbar decompression with posterior fixation 1 year prior. On examination, there were signs of thoracic myelopathy. Imaging revealed his previous instrumentation, pseudoarthrosis, and cord compression. We perform a two-staged operation to address the thoracic spinal cord compression and myelopathy, pseudoarthrosis, and malalignment with a lack of global spinal harmony. His imaging is driven by a spatial computing and SC environment and offers support for the diagnosis of his L2-3 and L4-5 pseudoarthrosis on the reconstructed SC-based computed tomography scan. SC enabled the assessment of the configuration of the psoas muscle and course of critical neurovascular structures in addition to graft sizing, trajectory and approach, evaluation of the configuration and durability of the anterior longitudinal ligament, and the overlying abdominal viscera. SC increases the familiarity of the patient's specific anatomy and enhances perioperative assessment. As such, SC can be used to preoperatively plan for spinal revision surgery.


VCAM1-targeted RNA interference inhibits the proliferation of human oral squamous carcinoma HN12 cells.
In the present study, RNA interference (RNAi) was used to investigate the effect of vascular cell adhesion molecule 1 (VCAM1) silencing on the proliferation of human oral squamous carcinoma HN12 cells. HN12 cells were divided into three groups: The untreated blank control cell group (CK), the negative control group transfected with non-homologous vector (NC) and the positive group transfected with the target sequence VCAM1 small hairpin RNA (KD). Reverse-transcription polymerase chain reaction and western blot analysis were used to examine the effects of VCAM1-knockdown on the mRNA expression of VCAM1 and subsequent protein expression. Furthermore, the HN12 cell growth inhibition rate was detected using the cell counting kit-8 method. The VCAM1-targeted lentiviral vector RNAi significantly inhibited VCAM1 mRNA, and subsequent protein, expression. Compared with the NC group, the VCAM1 gene knockdown efficiency was ~85%, while the expression level of VCAM1 protein was reduced by ~74% in KD group cells. In addition, cell growth was significantly inhibited in the KD group, with a growth inhibition rate of ~34%. Therefore, this targeted lentiviral vector RNAi effectively inhibited VCAM1 gene, and subsequent protein, expression, as well as the proliferation of oral squamous carcinoma cells. These results may provide an experimental reference for the diagnosis and treatment of oral squamous cell carcinoma.


Improvement in fear memory by histamine-elicited ERK2 activation in hippocampal CA3 cells.
Consolidation of associative memories appears to require extracellular signal-related kinase2 (ERK2) activation, which is modulated by several factors, including neurotransmitter receptor stimulation. Here we show that in vitro stimulation of either H2 or H3 histaminergic receptors activates ERK2 in hippocampal CA3 pyramidal cells. In behaving animals, bilateral posttraining injections into the dorsal hippocampus of histamine H2 or H3 receptor agonists improve memory consolidation after contextual fear conditioning. Local administration of U0126, a selective inhibitor of ERK kinase, prevents memory improvements exerted by the agonists, without causing any behavioral effect per se. This is the first evidence of a positive correlation between ERK phosphorylation and memory improvement. Moreover, we demonstrate that the brain histaminergic system regulates hippocampal ERK cascade. Finally, our data indicate that early ERK2 hippocampal activation is not required for the expression of long-term fear memories.


How to cluster gene expression dynamics in response to environmental signals.
Organisms usually cope with change in the environment by altering the dynamic trajectory of gene expression to adjust the complement of active proteins. The identification of particular sets of genes whose expression is adaptive in response to environmental changes helps to understand the mechanistic base of gene-environment interactions essential for organismic development. We describe a computational framework for clustering the dynamics of gene expression in distinct environments through Gaussian mixture fitting to the expression data measured at a set of discrete time points. We outline a number of quantitative testable hypotheses about the patterns of dynamic gene expression in changing environments and gene-environment interactions causing developmental differentiation. The future directions of gene clustering in terms of incorporations of the latest biological discoveries and statistical innovations are discussed. We provide a set of computational tools that are applicable to modeling and analysis of dynamic gene expression data measured in multiple environments.


Antagonism of alpha1-adrenoceptor agonist-induced responses by rilmenidine in vascular smooth muscle.
The effect of the centrally acting antihypertensive agent, rilmenidine, was examined on the contractile properties of isolated rat portal vein strips and on the free cytosolic [Ca2+] ([Ca2+]i) in isolated myocytes. Rilmenidine (1-30 microM) relaxed strips precontracted with noradrenaline. This effect was not inhibited by the alpha2-adrenoceptor antagonist, yohimbine, and was not mimicked by the alpha2-adrenoceptor agonist, 5-bromo-N-(4,5-dihydro-1H-imidazol-2-yl)-6-quinoxalinamine (UK 14,304). Rilmenidine dose dependently shifted to the right the concentration-response curves to noradrenaline and to phenylephrine but not that to carbachol. Rilmenidine alone (0.1-30 microM) caused a contraction which maximally corresponded to 18% of the maximal noradrenaline-induced contraction. This effect was not produced by UK 14,304, was not affected by yohimbine, but was inhibited by the alpha1-adrenoceptor antagonist, prazosin. In isolated myocytes, rilmenidine reduced the noradrenaline-induced [Ca2+]i increase but alone, it produced a rise in [Ca2+]i, the peak amplitude of which averaged 15% of the noradrenaline-induced transient [Ca2+]i rise. It is concluded that rilmenidine acts as a partial agonist of alpha1-adrenoceptors of vascular smooth muscle, causing relaxation of vessels precontracted by full agonists of alpha1-adrenoceptors.


[Changes of the microcirculatory blood perfusion at "Feishu" (BL 13) in the COPD rats].
To observe the change of the specificity of the microcirculatory blood perfusion at the area of "Feishu" (BL 13) in the rats of chronic obstructive pulmonary disease (COPD). According to the random number table, 60 Wistar rats were divided into a 29 d model No. 1 group (C1 group), a 29 d normal control No.1 group (N1 group), a 89 d model No.2 group (C2 group) and a 89 d normal control No. 2 group (N2 group), 15 rats in each one. In the C1 and C2 groups, the smoking and intratracheal drops of endotoxin were used in combination to prepare COPD model. The rats were fed normally in the N1 and N2 groups. "Feishu" (BL 13), "Xinshu" (BL 15), the lateral site of "Feishu" (BL 13) and the lateral site of "Xinshu" (BL 15) were selected as the monitoring points. The pericam perfusion speckle imager (PeriCam PSI System) was adopted to monitor the microcirculatory perfusion unit (PU) at the monitoring points before and in 29 d and 89 d after modeling separately. Before modeling, the differences in PU were not significant at each monitoring point in comparison among the 4 groups and the differences were not significant among "Feishu" (BL 13) and "Xinshu" (BL 15) as well as their lateral sites (all P>0.05). After modeling, PU was increased at each monitoring point in the C1 and C2 groups (all P<0.05). PU in the C1 group was higher than the N1 group and that in the C2 group was lower than the N2 group, PU at each monitoring point in the C1 group were higher than the C2 group, indicating the significant differences (all P<0.05). In the C1 and C2 groups, the specific change occurred, in which PU at "Feishu" (BL 13) was higher than its lateral site. But such specific change did not happen in the N1 and N2 groups. PU at "Feishu" (BL 13) presents the specific change relevant with the sickness duration in the COPD rats.


[Comparison of the antitussive effect of two different drugs regarding frequency and strength of cough attacks (author's transl)].
The antitussive effect of two different drugs A (Codeine, Phenyltoloxamine) and B (Dihydrocodeine, Remedacen) was compared in a double blind clinical trial by measuring the frequency and strength of cough attacks for 7 hours. The cough attacks were measured by a pressure-monitoring device which was externally fastened to the throat. Drug B suppressed the strenght and frequency for at least 9 hours after application while the effectiveness of drug A lasted only for about 6 hours after application. In any case the respiratory drive was unaffected.


The Comparison of Metagenomic Next-Generation Sequencing with Conventional Microbiological Tests for Identification of Pathogens and Antibiotic Resistance Genes in Infectious Diseases.
Metagenomic next-generation sequencing (mNGS) has been widely studied, due to its ability of detecting all the microbial genetic information unbiasedly in a sample at one time and not relying on traditional culture. However, the application of mNGS in the diagnosis of clinical pathogens remains challenging. From December 2019 to March 2021, 134 specimens including Broncho alveolar lavage fluid (BAFL), blood, sputum, cerebrospinal fluid (CSF), bile, pleural fluid, pus, were continuously collected in The First Hospital of Qinhuangdao, and their retrospective diagnoses were classified into infectious disease (128, 95.5%) and noninfectious disease (6, 4.5%). The pathogen-detection performance of mNGS was compared with conventional microbiological tests (CMT) and culture method. In addition, the antibiotic resistance genes (ARGs) and evolutionary relationship of common drug-resistant A. baumannii were also analyzed. Compared with CMT and culture methods, mNGS showed higher sensitivity in pathogen detection (74.2% vs 57.8%; P < 0.001 and 66.3% vs 31.7%; P < 0.001, respectively). Importantly, for cases that mNGS-positive only, 18 (35%) cases result in diagnosis modification, and 7 (23%) cases confirmed the clinical diagnosis. In 17 cases that A. baumannii were both detected in mNGS and culture, ade genes were the most frequently detected ARGs (from 13 cases), followed by sul2 and APH(3")-Ib (both from 12 cases). High consistency was observed among these ARGs and the related phenotype (100% for ade genes, 91.6% for sul2 and APH(3")-Ib). A. baumannii strains were classified into three groups, and most were well-clustered. It suggested those strains may be the epidemic strains. In our study, mNGS had a higher sensitivity than CMT and culture method. And the result of ARGs frequency and cluster analysis of A. baumannii was of great significance to the anti-infective therapy.


Status of home blood pressure measured in morning and evening: evaluation in normotensives and hypertensives in Japanese urban population.
To assess home blood pressure status in a Japanese urban population, we analyzed home blood pressure values in normotensive subjects determined by casual blood pressure (< 140/90 mmHg), hypertensive subjects without medication (> or = 140/90 mmHg) and treated hypertensive patients. The subjects (468 male, 232 female; mean age 41 years old) were recruited from a company located in Tokyo. Home blood pressure was measured with a semi-automatic device (Omron HEM-759P). Subjects were instructed to perform triplicate morning and evening measurements on 7 consecutive days. In the treated hypertensive group (n = 70), there was a significant difference between morning (139 +/- 12/88 +/- 9 mmHg) and evening (130 +/- 12/79 +/- 8 mmHg) home blood pressure. In the normotensive group (n = 558), however, only the diastolic blood pressure (DBP) component of the home blood pressure was significantly different between morning (115 +/- 13/72 +/- 9 mmHg) and evening (114 +/- 12/68 +/- 8 mmHg). In the nontreated hypertensive group (n = 72), casual blood pressure (145 +/- 14/92 +/- 9 mmHg) was higher than morning (138 +/- 16/89 +/- 11 mmHg) and evening (134 +/- 16/83 +/- 11 mmHg) home blood pressure, but no difference was seen between morning and evening systolic blood pressure (SBP). According to the reference value of the Japanese Society of Hypertension 2004 (SBP > or = 135 mmHg and/or DBP > or = 85 mmHg), 7.2% (systolic) and 8.7% (diastolic) of subjects in the normotensive group were classified as hypertensive by home blood pressure. Casual blood pressure in the treated hypertensive group was normal in 64.3% for SBP and 70.0% for DBP. However, their morning SBP (32.9%), morning DBP (40.0%), evening SBP (10.0%), and evening DBP (17.1%) were classified as hypertensive by home blood pressure. Furthermore, patients who were taking antihypertensive drug(s) only in the morning (n = 52) showed higher morning SBP (6 mmHg, p = 0.086) and morning DBP (6 mmHg, p = 0.005) than patients taking drug(s) by other administration schedules (n = 18), but no difference in evening home blood pressure was observed. In conclusion, a proportion of the subjects defined as normotensive by casual blood pressure were classified as hypertensive by home blood pressure in the present urban population. Furthermore, morning home blood pressure control in the treated hypertensive group classified as under control by casual blood pressure was insufficient, especially in patients who were taking medication only in the morning.


Distributions of pore sizes and atomic densities in binary mixtures revealed by molecular dynamics simulations.
We report on the results of a molecular dynamics simulation study of porous glassy media, formed in the process of isochoric rapid quenching from a high-temperature liquid state. The transition to a porous solid occurs due to the concurrent processes of phase separation and material solidification. The study is focused on topographies of the model porous structures and their dependence on temperature and average density. To quantify the pore-size distributions, we put forth a scaling relation that provides a satisfactory data collapse in systems with high porosity. We also find that the local density of the solid domains in the porous structures is broadly distributed, and, with increasing average density, a distinct peak in the local density distribution is displaced toward higher values.


Soft-Tissue Grafting Techniques Associated With Immediate Implant Placement.
Immediate implant placement often presents challenges in terms of predictably obtaining soft-tissue coverage over the implant site. While delayed implant placement offers the ability for soft tissues to grow and invade the extraction socket making their attachment around implants more predictable, immediate implant placement poses a significant risk of bacterial invasion towards the implant surface as a result of insignificant soft-tissue volume. Soft-tissue grafting techniques have often been proposed for use during immediate implant placement to augment soft-tissue deficiencies, including the use of either palatal connective tissue grafts (CTGs) or collagen-derived scaffolds. However, both of these approaches have significant drawbacks in that CTGs are harvested with high patient morbidity and collagen scaffolds remain avascular and acelluar posing a risk of infection/implant contamination. More recently, platelet-rich fibrin (PRF) has been proposed as an economical and biological means to speed soft-tissue wound healing. In combination with immediate implant placement, PRF offers an easily procurable low-cost regenerative modality that offers an efficient way to improve soft-tissue attachment around implants. Furthermore, the supra-physiological concentration of defense-fighting leukocytes in PRF, combined with a dense fibrin meshwork, is known to prevent early bacterial contamination of implant surfaces, and the biological concentrations of autologous growth factors in PRF is known to increase tissue regeneration. This article discusses soft-tissue grafting techniques associated with immediate implant placement, presents several cases demonstrating the use of PRF in routine immediate implant placement, and further discusses the biological and economic advantages of PRF for the management of soft-tissue grafting during immediate implant placement.


Heme modulates Trypanosoma cruzi bioenergetics inducing mitochondrial ROS production.
Trypanosoma cruzi is the causative agent of Chagas disease and has a single mitochondrion, an organelle responsible for ATP production and the main site for the formation of reactive oxygen species (ROS). T. cruzi is an obligate intracellular parasite with a complex life cycle that alternates between vertebrate and invertebrate hosts, therefore the development of survival strategies and morphogenetic adaptations to deal with the various environments is mandatory. Over the years our group has been studying the vector-parasite interactions using heme as a physiological oxidant molecule that triggered epimastigote proliferation however, the source of ROS induced by heme remained unknown. In the present study we demonstrate the involvement of heme in the parasite mitochondrial metabolism, decreasing oxygen consumption leading to increased mitochondrial ROS and membrane potential. First, we incubated epimastigotes with carbonyl cyanide p-(trifluoromethoxy) phenylhydrazone (FCCP), an uncoupler of oxidative phosphorylation, which led to decreased ROS formation and parasite proliferation, even in the presence of heme, correlating mitochondrial ROS and T. cruzi survival. This hypothesis was confirmed after the mitochondria-targeted antioxidant ((2-(2,2,6,6 Tetramethylpiperidin-1-oxyl-4-ylamino)-2-oxoethyl) triphenylphosphonium chloride (MitoTEMPO) decreased both heme-induced ROS and epimastigote proliferation. Furthermore, heme increased the percentage of tetramethylrhodamine methyl ester (TMRM) positive parasites tremendously-indicating the hyperpolarization and increase of potential of the mitochondrial membrane (ΔΨm). Assessing the mitochondrial functional metabolism, we observed that in comparison to untreated parasites, heme-treated epimastigotes decreased their oxygen consumption, and increased the complex II-III activity. These changes allowed the electron flow into the electron transport system, even though the complex IV (cytochrome c oxidase) activity decreased significantly, showing that heme-induced mitochondrial ROS appears to be a consequence of the enhanced mitochondrial physiological modulation. Finally, the parasites that were submitted to high concentrations of heme presented no alterations in the ultrastructure. Consequently, our results suggest that heme released by the insect vector after the blood meal, modify epimastigote mitochondrial physiology to increase ROS as a metabolic mechanism to maintain epimastigote survival and proliferation.


The Validity and Reliability of the Thanatophobia Scale-Turkish Form: A Psychometric Study Among Nurses.
Purpose: To examine the validity and reliability of the Thanatophobia Scale-Turkish Form among nurses. Design and methods: This methodological study included 154 nurses. Content and construct validity, item analysis, confirmatory factor analysis, and internal consistency were used to evaluate the data. Findings: The content validity index of the scale was 0.91. Item-total score correlation values varied between 0.453 and 0.718. As a result of the confirmatory factor analyses, one factor was confirmed. Cronbach's alpha internal consistency coefficient was 0.854. Practice Implications: Thanatophobia Scale-Turkish Form is a valid and reliable tool used to evaluate the fear of death among nurses.


Occasional finding of mesenteric lipodystrophy during laparoscopy: a difficult diagnosis.
Mesenteric lipodystrophy is a rare pathological condition affecting the mesentery. Its initial presentation is typically asymptomatic. Pathological characteristics are unspecific, and generally attributed to inflammation, unless the diagnosis is suspected. Laparoscopy done for other reasons has been, as in this case, unsuccessful in providing evidence for the correct diagnosis, thus requiring laparotomy due to lack of diagnostic tissue. After 6 mo no further medical therapy is required, as the patient remains asymptomatic. Discussion of this case and a brief review of the literature are presented in the following paragraphs.


Localized juvenile spongiotic gingival hyperplasia.
We report 52 cases of a unique and pathologically distinctive form of inflammatory gingival hyperplasia in young patients. Clinically, the average age of patients in this study was 11.8 years, with a 2.3:1 female predominance. Caucasians comprised 77% of the cases, and nearly all of the lesions were located on the anterior gingiva, with 81% affecting maxillary gingiva. The most classic clinical presentation was a papillary, often pedunculated, red and easily bleeding gingival overgrowth in young patients. Histopathologically, the lesions exhibited a subtle papillary epithelial hyperplasia with prominent intercellular edema and neutrophilic exocytosis of the hyperplastic surface squamous epithelium. Based on the characteristic clinical and histologic features, we conclude that this lesion is a distinct subtype of gingival hyperplasia. Although previously described as juvenile spongiotic gingivitis, we propose the term localized juvenile spongiotic gingival hyperplasia as a more accurate designation.


Regulation of osteoclastogenesis by ganoderic acid DM isolated from Ganoderma lucidum.
The preventative effects of the ethanol extracts of Ganoderma lucidum against the ovariectomized (Ovx)-induced deterioration of bone density in 11-week-old female Sprague Dawley (SD) rats were investigated. The results showed that the G. lucidum-treated Ovx rats showed improved bone density compared with the Ovx rats. We studied the effects of G. lucidum on osteoclastic differentiation using bone marrow cells and RAW 264 cell D-clone (RAW-D). Differentiation, in response to receptor activator of NF-kappaB ligand (RANKL) and a tumor necrosis factor alpha (TNF-alpha), was inhibited by the ethanol extracts of G. lucidum and ganoderic acid DM which was isolated as one of the active compounds by bioassay-guided fractionation. Ganoderic acid DM especially suppresses the expression of c-Fos and nuclear factor of activated T cells c1 (NFATc1). This suppression leads to the inhibition of dendritic cell-specific transmembrane protein (DC-STAMP) expression and reduces osteoclast fusion.


Exploring Methods of Targeting Histone Methyltransferases and Their Applications in Cancer Therapeutics.
Histone methyltransferases (HMTs) are enzymes that catalyze the methylation of lysine or arginine residues of histone proteins, a key post-translational modification (PTM). Aberrant expression or activity of these enzymes can lead to abnormal histone methylation of cancer-related genes and thus promote tumorigenesis. Histone methyltransferases have been implicated in chemotherapeutic resistance and immune stimulation, making these enzymes potential therapeutic targets of interest, and chemically targeting these proteins provides an avenue for novel drug development in cancer therapy. This Review aims to discuss the evolution of chemical approaches that have emerged in the past five years to design probes targeting these enzymes, including inhibition through noncovalent inhibitors, covalent inhibitors, and targeted protein degradation through proteolysis targeting chimeras (PROTACs). This Review also highlights how these compounds have been used to study the myriad of HMT functions in cancer progression and treatment response. The recent advancement of some of these drugs into human clinical investigation and even to regulatory approval highlights HMTs as a promising class of targets for chemical intervention and novel therapy development.


Urinary peptide-based classifier CKD273: towards clinical application in chronic kidney disease.
Capillary electrophoresis coupled with mass spectrometry (CE-MS) has been used as a platform for discovery and validation of urinary peptides associated with chronic kidney disease (CKD). CKD affects ∼ 10% of the population, with high associated costs for treatments. A urinary proteome-based classifier (CKD273) has been discovered and validated in cross-sectional and longitudinal studies to assess and predict the progression of CKD. It has been implemented in studies employing cohorts of > 1000 patients. CKD273 is commercially available as an in vitro diagnostic test for early detection of CKD and is currently being used for patient stratification in a multicentre randomized clinical trial (PRIORITY). The validity of the CKD273 classifier has recently been evaluated applying the Oxford Evidence-Based Medicine and Southampton Oxford Retrieval Team guidelines and a letter of support for CKD273 was issued by the US Food and Drug Administration. In this article we review the current evidence published on CKD273 and the challenges associated with implementation. Definition of a possible surrogate early endpoint combined with CKD273 as a biomarker for patient stratification currently appears as the most promising strategy to enable the development of effective drugs to be used at an early time point when intervention can still be effective.


A Solitary Spinal Cord Metastasis From Lung Cancer Displayed on 18 F-FDG PET/CT.
Chest CT images were acquired in a 79-year-old man to evaluate a right lung mass revealed by chest radiography. The image findings suggested possible pulmonary malignancy. FDG PET/CT was performed for staging, which displayed not only a hypermetabolic mass in the upper lobe of right lung but also increased FDG uptake of the spinal cord at T11 to T12 level. A lesion corresponding to the hypermetabolic region of the spinal cord was revealed by MRI. The intramedullary spinal cord metastasis from lung squamous cell carcinoma was confirmed through the pathological examination after the spinal cord lesion was resected.


Conformational changes in HIV-1 gp41 in the course of HIV-1 envelope glycoprotein-mediated fusion and inactivation.
HIV-1 envelope glycoprotein-mediated fusion is driven by the concerted coalescence of the HIV-1 gp41 N- and C-helical regions, which results in the formation of 6-helix bundles. These two regions are considered prime targets for peptides and antibodies that inhibit HIV-1 entry. However, the parameters that govern this inhibition have yet to be elucidated. We address this issue by monitoring the temporal sequence of conformational states of HIV-1 gp41 during the course of HIV-1-mediated cell-cell fusion by quantitative video microscopy using reagents that bind to N- and C-helical regions, respectively. Env-expressing cells were primed by incubation with target cells at different times at 37 degrees C followed by washing. The reactivity of triggered gp41 to the NC-1 monoclonal antibody, which we demonstrate here to bind to N-helical gp41 trimers, increased rapidly to a maximal level in the primed state but decreased once stable fusion junctions had formed. In contrast, reactivity with 5-helix, which binds to the C-helical region of gp41, increased continuously as a function of time following the priming. The peptide N36(Mut(e,g)) reduced NC-1 monoclonal antibody binding and enhanced 5-helix binding, consistent with the notion that this molecule promotes dissociation of gp41 trimers. This inactivation pathway may be important for the design of entry inhibitors and vaccine candidates.


Properties of nicotinic receptors underlying Renshaw cell excitation by alpha-motor neurons in neonatal rat spinal cord.
We used anatomical and physiological approaches to characterize nicotinic receptors (AChRs) on Renshaw cells of the neonatal rat spinal cord. Confocal imaging of Renshaw cells, identified by their characteristic pattern of gephyrin immunoreactivity, revealed that these neurons are immuno-positive for the alpha4 and beta2 AChR subunits but not for the alpha7 subunit. We used whole cell recording in spinal cord slices to characterize synaptic transmission from alpha-motor neurons to Renshaw cells, which could be identified pharmacologically by the sensitivity of transmission to d-tubocurarine. alpha-Motor neuron-to-Renshaw cell synapses were blocked by 10 microM dihydro-beta-erythroidine (dHbetaE), but not 50 nM methyllycaconitine (MLA), a selective alpha7 antagonist. These findings support a role for alpha4beta2-like AChRs, but not alpha7 AChRs, in rapid excitatory transmission between alpha-motor neurons and Renshaw cells in rat spinal cord.


An examination of the psychometric properties of the Chinese version of the Barratt Impulsiveness Scale, 11th version in a sample of Chinese adolescents.
The current study examined the psychometric properties of the Chinese translation of the Barratt Impulsiveness Scale 11th version in a sample of adolescents from Hunan province, mainland China. During an initial assessment, 396 secondary school students (Grades 10-12) completed the scale and self-report measures assessing problem behaviors and alcohol use. The scale was re-administered 1 mo. later. Analysis gave Cronbach alpha of .80 and test-retest reliability of .70. Confirmatory factor analysis indicated a model containing six first-order factors and two second-order factors best fit the data. Girls reported higher Total scores than boys as well as higher scores on the motor impulsiveness, self-control, and cognitive instability sub-scales. Scores were associated in the predicted direction with a wide variety of self-reported problem behaviors including alcohol use, gambling, and academic misconduct. Current findings indicate that the translated scale is a promising tool with some further development for assessing impulsiveness with Chinese adolescents.


Critical issues for effective collaboration between academia and industry in the field of regenerative medicine in Japan.
To identify which factors are important barriers to effective collaboration between Japanese academia and industry in the field of regenerative medicine. In November-December 2006, in-person semistructured interviews were conducted with representatives from nine Japanese companies that are engaged in developing regenerative medicine products in collaboration with academia and two academic scientists with the successful collaborative experiences with companies. The major barriers to collaboration relate to the inadequacy of particular systems in academic institutions (particularly technology licensing organizations and mobility between industry and academia), the knowledge deficit of academic personnel with respect to industry, the inadequacy of particular governmental support systems and the Japanese public's view of these collaborations, which has resulted in overly strict conflict of interest guidelines. We suggest some approaches to overcome these barriers.


Mandibular Reconstruction in Ameloblastoma Using Allogeneic Cord Stem Cells and Alloplastic Graft Material - Case Report.
Ameloblastoma is a histologically benign odontogenic tumour and has a tendency of locally aggressive behaviour. This is second most prevalent odontogenic tumour and most common in the molar-ramus-angle region and surgical resection is only treatment option. In this article, we propose an innovative approach to deal with these cases by using alloplastic graft with cord stem cells. Over 2.5 years follow-up, we could demonstrate bone regeneration using this technique with no recurrence. To the best of our knowledge, this is the first report of successful regeneration of part of ramus and body of mandible using allogeneic cord stem cells in cases of Ameloblastoma.


[Characteristics of the factors that suppress and stimulate interferon production].
A repressor of interferon production is contained in the hyaloplasm of the chick embryo fibroblast cells in the state of hyporeactivity. A factor stimulating interferon production (FSIP) was found in the hyaloplasm of the cells subjected to single or double induction with poly (pI) x poly (pC) followed by exposure to actinomycin D. Both preparations were of the protein nature and possessed high biological activity. They repressed or stimulatd interferon production at a dilution of 1:512-1:1024. The preparations had tissue and inductor specificity, did not affect the Venezuelan equine encephalomyelitis virus and interferon antiviral activity. Unlike the repressor, the FSIP proved to be thermolabile and pH-sensitive in acid media. The half lives of the repressor and stimulator were about 10 and 5 hours respectively.


A distinct class of inducible murine type-C viruses that replicates in the rabbit SIRC cell line.
The existence of the selectively permissive rabbit cell line SIRC allows definition of a new class of endogenous murine type-C virus. Continuous clonal lines of transformed cells derived from the BALB/c mouse-embryo cell line BALB/3T3 contain at least two distinct classes of endogenous type-C viral genomes. Spontaneously released endogenous viruses grow well on the mouse cell line NIH/3T3 (N-tropic viruses) but not on the rabbit cell line SIRC. Type-C viruses induced by treatment with BrdU grow well on SIRC (S-tropic viruses) but not in NIH/3T3 or BALB/3T3. BrdU-treated AKR mouse-embryo cells also release an S-tropic virus. N-tropic and S-tropic viruses both have the mouse intraspecies gs-1 and viral RNA-directed DNA polymerase antigenic determinants. DNA.RNA hybridization techniques reveal that the two host-range classes of endogenous viruses are only partially related to each other. Cell transformation facilitates the spontaneous release of the N-tropic viruses; treatment with thymidine analogues induces the production of the S-tropic viruses. Thus, the two classes of viral genomes appear to be subject to different cellular controls.


Association between learning capabilities and practice-related activation changes in schizophrenia.
The present functional magnetic resonance imaging study investigated the neural correlates of practice-associated activation changes in patients with schizophrenia and their association with symptom severity. A group of patients (n = 24) were divided into more successful and less successful learners and were asked to perform a verbal overlearning task in the scanner. We found that both patient groups profited from practice, showing significant decreases in mean response times as well as significant learning-related decreases in cerebral activation. Direct comparison between groups yielded a relative hyperactivation in the group of the less successful learners at the beginning of practice, which showed a reduction with increasing practice. This was reflected by relatively stronger signal decreases in a predominantly fronto-parieto-cerebellar network. In the group of less successful learners, there was a negative correlation between general symptom scores and learning-related signal decreases in a task-relevant network involving cerebellar, inferior and middle frontal (BA 45/47, 46), superior parietal (BA 31), and superior temporal (BA 39) regions. Present data indicate that hyperactivity under high task demands might serve to identify those patients with less potential to profit from practice. However, at least in the context of moderate- to low-working memory demands, this activation abnormality seems to constitute a state rather than a trait characteristic, which patients manage to reduce by successful short-term learning. The findings also suggest that successful learners can better compensate potentially interfering effects exerted by disorder-related psychopathology.


Growth-promoting activity of tuna growth hormone and expression of tuna growth hormone cDNA in Escherichia coli.
Tuna (Thunnus thynnus) growth hormone (GH) was purified by using a column of Sepharose 4B to which tuna GH-specific IgG was linked. The molecular weight and isoelectric point of tuna GH were 21,000 and 6.5, respectively. The growth of snapper (Pagrus major) was remarkably accelerated when the purified hormone was administered by four intraperitonial injections at intervals of 5 days: 1.5-fold in length and 1.9-fold in body weight/60 days. To produce tuna GH in Escherichia coli cells, expression plasmids pTES8 and pTES8S for tuna GH cDNA with or without the signal peptide region were constructed and GH production in E. coli cells was examined with the Maxicell system. The product specified by the plasmids in E. coli cells was immunologically identified to be tuna GH.


Inhibitory circuits for visual processing in thalamus.
Synapses made by local interneurons dominate the intrinsic circuitry of the mammalian visual thalamus and influence all signals traveling from the eye to cortex. Here we draw on physiological and computational analyses of receptive fields in the cat's lateral geniculate nucleus to describe how inhibition helps to enhance selectivity for stimulus features in space and time and to improve the efficiency of the neural code. Further, we explore specialized synaptic attributes of relay cells and interneurons and discuss how these might be adapted to preserve the temporal precision of retinal spike trains and thereby maximize the rate of information transmitted downstream.


Validity of the new American College of Rheumatology criteria for neuropsychiatric lupus syndromes: a population-based evaluation.
To assess the validity of the recently developed American College of Rheumatology (ACR) nomenclature for neuropsychiatric systemic lupus erythematosus (NPSLE). We conducted a cross-sectional, population-based study covering an area with 440,000 people. A total of 46 patients aged 16 to 65 years fulfilled the criteria for a definite diagnosis of SLE. One control for each patient matched by age, sex, education, and place of residence was randomly identified from the population register. All patients and controls underwent a clinical neurologic examination and neuropsychological testing. The data were analyzed using conditional logistic regression methods. Forty-two patients (91%) and 25 controls (56%) fulfilled at least one of the ACR NPSLE criteria, which gave an odds ratio (OR) of 9.5 (95% confidence interval [CI] 2.2-40.8) but low specificity (0.46). Cognitive dysfunction was the most common syndrome detected in 37 patients (80%). A revised set of 16 criteria excluding the syndromes without evidence for neuronal damage resulted in improved specificity (OR 7.0, 95% CI 2.1-23.5, specificity 0.93). The proposed 19 ACR criteria did not differentiate SLE patients from controls, nor NPSLE patients from other SLE patients. The revised NPSLE criteria proposed by us performed well in our population but should be evaluated in a larger patient population.


Meningoencephalitis caused by Streptococcus pneumoniae: a diagnostic and therapeutic challenge. Diagnosis with diffusion-weighted MRI leading to treatment with corticosteroids.
Streptococcus pneumoniae is a common cause of bacterial meningitis but only rarely causes other infections such as brain abscess, encephalitis, encephalomyelitis or meningoencephalitis. We report on three adult patients with meningoencephalitis caused by S. pneumoniae. In all three, CT and MRI revealed widespread brain lesions, suggesting extensive parenchymal injury. Diffusion-weighted MRI showed lesions with restricted diffusion, reflecting local areas of ischaemia with cytotoxic oedema secondary to an immunologically mediated necrotising vasculitis and thrombosis. High levels of markers of neuronal, glial and myelin damage were found in the cerebrospinal fluid. According to the literature, brain parenchyma lesions in adults with pneumococcal meningoencephalitis are often associated with death or severe neurological deficit. Our patients were treated with pulse doses of glucocorticoids: this resulted in dramatic clinical improvement and an excellent final neurological recovery.


MCP-1 mRNA expression in basal keratinocytes of psoriatic lesions.
In addition to hyperproliferation of keratinocytes, psoriasis is characterized by pronounced leukocytic infiltration. In contrast to the epidermal localization of neutrophils and T lymphocytes, macrophages are almost exclusively restricted to the dermal compartment. By immunohistologic analysis, these dermal macrophages were mainly encountered in the papillary dermis and arranged along the rete ridges in close proximity to proliferating keratinocytes. Monocyte chemoattractant protein (MCP-1) anti-sense RNA probes yielded abundant signals over the proliferating basal keratinocytes of the tips of the rete ridges, and, to a lesser extent, in cells in the papillae. Thus, the strongest MCP-1 message in psoriatic lesions is found above the dermal-epidermal junction and this may explain the characteristic sub-basal distribution of dermal macrophages. These results suggest that MCP-1 is important in regulating the interaction between proliferating keratinocytes and dermal macrophages in psoriasis pathogenesis.


Modulation of the Gut Microbiota in Rats by Hugan Qingzhi Tablets during the Treatment of High-Fat-Diet-Induced Nonalcoholic Fatty Liver Disease.
Accumulative evidence showed that gut microbiota was important in regulating the development of nonalcoholic fatty liver disease (NAFLD). Hugan Qingzhi tablet (HQT), a lipid-lowering and anti-inflammatory medicinal formula, has been used to prevent and treat NAFLD. However, its mechanism of action is unknown. The aim of this study was to confirm whether HQT reversed the gut microbiota dysbiosis in NAFLD rats. We established an NAFLD model of rats fed with a high-fat diet (HFD), which was given different interventions, and measured the level of liver biochemical indices and inflammatory factors. Liver tissues were stained with hematoxylin-eosin and oil red O. Changes in the gut microbiota composition were analyzed using 16S rRNA sequencing. The hepatic histology and biochemical data displayed that HQT exhibited protective effects on HFD-induced rats. Moreover, HQT also reduced the abundance of the Firmicutes/Bacteroidetes ratio in HFD-fed rats and modified the gut microbial species at the genus level, increasing the abundances of gut microbiota which were reported to have an effect on relieving NAFLD, such as Ruminococcaceae, Bacteroidales_S24-7_group, Bifidobacteria, Alistipes, and Anaeroplasma, and significantly inhibiting the relative abundance of Enterobacteriaceae, Streptococcus, Holdemanella, Allobaculum, and Blautia, which were reported to be potentially related to NAFLD. Spearman's correlation analysis found that [Ruminococcus]_gauvreauii_group, Lachnoclostridium, Blautia, Allobaculum, and Holdemanella exhibited significant (p < 0.001) positive correlations with triglyceride, cholesterol, low-density lipoprotein cholesterol, interleukin-6, interleukin-1β, tumor necrosis factor-α, and body weight and negative correlations with high-density lipoprotein cholesterol (p < 0.001). The norank_f__Bacteroidales_S24-7_group and Alistipes showed an opposite trend. Moreover, the HQT could promote flavonoid biosynthesis compared with the HFD group. In summary, the HQT has potential applications in the prevention and treatment of NAFLD, which may be closely related to its modulatory effect on the gut microbiota.


A Direct Comparison of Self-Expandable Portico Versus Balloon-Expandable Sapien 3 Devices for Transcatheter Aortic Valve Replacement: A Case-Matched Cohort Study.
Pairwise comparisons of clinical and hemodynamic outcomes with new transcatheter aortic valve replacement (TAVR) prostheses are needed to help interventionists select the most appropriate device. The self-expandable Portico valve (Abbott Vascular) was compared with the balloon-expandable Sapien 3 valve (Edwards Lifesciences) at a high-volume center in a real-world setting. All patients undergoing TAVR with a new-generation device from March 2015 to September 2017 at a single center were included. Baseline, peri-interventional, and prospective 30-day follow-up data were obtained. A nearest-neighbor propensity-score matching procedure (2:1) was used, based on age, STS score, EuroScore II, New York Heart Association (NYHA) status, and sex. Primary endpoint was 30-day all-cause mortality. Secondary endpoints included procedural results, complications according to Valve Academic Research Consortium (VARC)-2 criteria, and echocardiographic findings. A total of 177 out of 273 patients were matched (104 Portico valves and 73 Sapien 3 valves). Procedural success rates were 99.0% vs 98.6%, respectively; P=NS). Contrast dye use (160 mL for Portico vs 120 mL for Sapien 3; P<.001) and fluoroscopy time (19.0 min for Portico vs 15.5 min for Sapien 3; P=.048) were significantly lower with the Sapien 3 device. Thirty-day mortality rate was 5.8% for the Portico group vs 4.1% for the Sapien 3 group (P=.74). Complication rates were similar between Portico and Sapien 3 groups: stroke (2.9% vs 4.1%, respectively; P=.31), major bleeding (3.8% vs 5.5%, respectively; P=.51), major vascular complications (5.8% vs 5.5%, respectively; P=.99), and pacemaker implantation (21.9% vs 17.5%, respectively; P=.55). A more-than-mild paravalvular leak was observed in 8.2% vs 4.5%, respectively (P=NS). Short-term clinical and hemodynamic outcomes were similar with Portico and Sapien 3 prostheses; no statistically significant differences were observed in mortality and major complication rates. An individually tailored prosthesis choice is suggested.


Photovoltaic properties of GaAsP core-shell nanowires on Si(001) substrate.
We report on the growth and electro-optical studies of photovoltaic properties of GaAsP nanowires. Low density GaAsP nanowires were grown by Au assisted MOVPE on Si(001) substrates using a two step procedure to form a radial p-n junction. The STEM analyses show that the nanowires have cubic structure with the alloy composition GaAs₀.₈₈P₀.₁₂ in the nanowire core and GaAs₀.₇₆P₀.₂₄ in the shell. The nanowire ensembles were processed in the form of sub-millimeter size mesas. The photovoltaic properties were characterized by optical beam induced current (OBIC) and electronic beam induced current (EBIC) maps. Both OBIC and EBIC maps show that the photovoltage is generated by the nanowires; however, a strong signal variation from wire to wire is observed. Only one out of six connected nanowires produce a measurable signal. These strong fluctuations can be tentatively explained by the variation of the resistance of the nanowire-to-substrate connection, which is highly sensitive to the quality of the Si-GaAsP interface. This study demonstrates the importance of the spatially resolved charge collection microscopy techniques for the diagnosis of failures in nanowire photovoltaic devices.


Music imagery for adults with acute leukemia in protective environments: a feasibility study.
Patients receiving intensive chemotherapy can experience increased distressed related to both the cancer diagnosis and treatment isolation. If not addressed, distress can lead to anxiety, depression, and post-traumatic stress disorder. The purpose of this study was to determine the feasibility and possible benefits of a music imagery intervention for patients hospitalized in a protective environment for the treatment of acute leukemia or high-grade non-Hodgkin's lymphoma. Adults receiving intensive myelosuppressive chemotherapy in a protective environment were randomized to standard care or standard care plus music imagery. The music imagery sessions occurred twice weekly for up to eight sessions. Patients were encouraged to use the music imagery daily. The principal criteria of feasibility were rate of consent, rate of completion of scheduled sessions, and rate of questionnaire completion. Forty-nine out of 78 patients consented, a 63% consent rate. Seventy-two percent of all scheduled music imagery sessions were completed. The rate of questionnaire completion was 60% with missing data because of illness severity and early discharge. The principal outcomes of benefit (e.g., efficacy) were positive and negative affects, fatigue, and anxiety. Both groups improved over time on all outcomes (all p < 0.001). However, a subgroup of individuals with low baseline negative affect who received the intervention reported significantly less anxiety at discharge than individuals with low baseline negative affect who did not receive the intervention. Music imagery is feasible for adults with acute leukemia in protected environments. Patients with lower initial distress may benefit from a music imagery program in terms of reduced anxiety at discharge.


Peptide sequences converting polyglutamine into a prion in yeast.
Amyloids are ordered protein aggregates composed of cross-β sheet structures. Amyloids include prions, defined as infectious proteins, which are responsible for mammalian transmissible spongiform encephalopathies, and fungal prions. Although the conventional view is that typical amyloids are associated with nontransmissible mammalian neurodegenerative diseases such as Alzheimer's disease, increasing evidence suggests that the boundary between transmissible and nontransmissible amyloids is ambiguous. To clarify the mechanism underlying the difference in transmissibility, we investigated the dynamics and the properties of polyglutamine (polyQ) amyloids in yeast cells, in which the polyQ aggregates are not transmissible but can be converted into transmissible amyloids. We found that polyQ had an increased tendency to form aggregates compared to the yeast prion Sup35. In addition, we screened dozens of peptides that converted the nontransmissible polyQ to transmissible aggregates when they flanked the polyQ stretch, and also investigated their cellular dynamics aiming to understand the mechanism of transmission.


Current Measurement Strategies of Coronal Tibiofemoral Subluxation: A Systematic Review of Literature.
OBJECTIVE. Coronal tibiofemoral (TF) subluxation has generated interest in the last several years due to newfound clinical implications of its presence. However, controversy within the literature concerning how to measure and calculate coronal TF subluxation on radiographic imaging remains. The purpose of this study was to describe how coronal TF subluxation is being measured and calculated in the literature with the goal of describing a reproducible and validated technique for clinical adoption. MATERIALS AND METHODS. A PubMed literature search was performed in March 2020 according to PRISMA guidelines. The terms "tibiofemoral subluxation" and "tibial femoral subluxation" were included in the search. Criteria of interest included radiographic view and evaluation, anatomic landmarks used, and measurement validity. RESULTS. Review of relevant literature resulted in 744 articles, 16 of which met our inclusion criteria. A wide range of measuring techniques, anatomic landmarks, and radiographic views were used with varying validity. Full-limb radiographic views were the most common. Six studies measured the translation of the mechanical axes of the tibia and femur. Eight studies measured the translation of either femoral condyle in reference to the tibial plateau. Coordinate-based software with the iterative closest point algorithm was used in two studies. Whether coronal TF subluxation should be divided by tibial plateau width to account for knee size was controversial. CONCLUSION. A variety of approaches exist for diagnosing and quantifying coronal TF subluxation because of the lack of clear anatomic landmarks within the TF joint that can be used to measure coronal TF subluxation in the horizontal plane. Even when using the same anatomic landmarks, studies varied on how to measure coronal TF subluxation radiographically and whether knee size should be accounted for. Further studies are necessary to standardize (via inter- and intraobserver validation with a control group) an easy, reproducible, and minimally biased approach to measuring coronal TF subluxation on radiographic imaging. We believe our systematic review succinctly provides the necessary information to either develop such a tool or encourage future studies to compare existing techniques to find the most reliable and clinically useful approach for evaluating coronal TF subluxation.


Vascular vertigo and dizziness: Diagnostic criteria.
This paper presents diagnostic criteria for vascular vertigo and dizziness as formulated by the Committee for the Classification of Vestibular Disorders of the Bárány Society. The classification includes vertigo/dizziness due to stroke or transient ischemic attack as well as isolated labyrinthine infarction/hemorrhage, and vertebral artery compression syndrome. Vertigo and dizziness are among the most common symptoms of posterior circulation strokes. Vascular vertigo/dizziness may be acute and prolonged (≥24 hours) or transient (minutes to < 24 hours). Vascular vertigo/dizziness should be considered in patients who present with acute vestibular symptoms and additional central neurological symptoms and signs, including central HINTS signs (normal head-impulse test, direction-changing gaze-evoked nystagmus, or pronounced skew deviation), particularly in the presence of vascular risk factors. Isolated labyrinthine infarction does not have a confirmatory test, but should be considered in individuals at increased risk of stroke and can be presumed in cases of acute unilateral vestibular loss if accompanied or followed within 30 days by an ischemic stroke in the anterior inferior cerebellar artery territory. For diagnosis of vertebral artery compression syndrome, typical symptoms and signs in combination with imaging or sonographic documentation of vascular compromise are required.


GLP-1(7-36)amide binding in skeletal muscle membranes from streptozotocin diabetic rats.
A higher specific binding of GLP-1(7-36)amide is found in skeletal muscle plasma membranes from adult streptozotocin (STZ)-treated rats (insulin-dependent diabetes mellitus model) and from neonatal STZ-treated rats (non insulin-dependent diabetes mellitus model), as compared to that in normal controls; no apparent change in the affinity was observed, that indicating the presence in both diabetic models of an increased number of high affinity binding sites for the peptide. The maximal specific GLP-1(7-16)amide binding in the non insulin-dependent diabetes mellitus model was found to be significantly higher than that in the insulin-dependent diabetes mellitus model. As GLP-1(7-36)amide exerts a glycogenic effect in the rat skeletal muscle, the present data suggest that the action of the peptide in the muscle glucose metabolism may be increased in states of insulin deficiency accompanied or not by insulin resistance.


Improving the Measurement of Fertility Regulation Practices: Findings from Qualitative Research in Ghana.
According to Demographic and Health Survey (DHS) data, highly educated urban women in some West African countries simultaneously have low rates of both contraceptive use and fertility-suggesting that the DHS may not be capturing a complete picture of women's contraceptive practices. Individual in-depth interviews and focus group discussions were conducted with a total of 48 women aged 18-49 in Accra, Ghana, who had at least a secondary education to explore their reproductive lives and relationships, and their views on and use of fertility regulation strategies. Data were analyzed using iterative thematic techniques. Women commonly reported using combinations of contraceptive methods, including "counting days" (using a calendar and the date of one's last menstrual period to estimate "unsafe" days-those on which the risk of conception is high), as well as withdrawal, condoms and frequent use of emergency contraceptive pills. Women described practicing "periodic contraception": for example, counting days to determine unsafe days and practicing contraception ad hoc on such days. Method use combinations varied from cycle to cycle-forming a "mosaic" of method use combinations over time. The fertility control strategies commonly reported by the study respondents-periodic contraception, and frequent use of traditional methods and emergency contraceptive pills-are likely not adequately captured in general surveys such as the DHS. Such surveys are also not well suited to measuring combinations of methods and mosaics of method combinations. New ways of capturing women's fertility regulation practices should be considered, including additional survey items, new question modules and specialist studies.


Blaming the victim: the effects of extraversion and information disclosure on guilt attributions in cyberbullying.
Cyberbullying victims' success in coping with bullying largely depends on schoolmates and other bystanders' social support. However, factors influencing the degree of social support have as yet not been investigated. In this article, the concept of victim blaming is applied to cyberbullying incidents. It is assumed that a cyberbullying victim receives less social support when the victim's behavior is perceived as very overt. It is further assumed that this effect's underlying process is the partial attribution of responsibility for the incident to the victim and not to the bully. The hypotheses are tested with a 2×2 online experiment. In this experiment, varying online self-presentations of a fictitious female cyberbullying victim were presented to 586 Germans aged 16-22. The victim's public Facebook profile was manipulated in terms of the victim's extraversion and the amount of personal information disclosed. The results support the hypotheses. Participants attributed more responsibility for the bullying incident to the victim when the victim was presented as extraverted and very open in revealing personal information. This diminished social support for the victim. The effect was partially mediated by the victim's perceived attractiveness. The study implies that concepts from victimization research can enhance our understanding of cyberbullying incidents. Among other factors, the victim's specific personal characteristics deserve more consideration--not only with regard to the incident itself but also regarding subsequent social dynamics and coping mechanisms.


Fallopian tube sperm perfusion (FSP) versus intra-uterine insemination (IUI) in the treatment of unexplained infertility: a prospective randomized study.
Prospective randomization of 60 couples with unexplained infertility was performed for treatment either with intrauterine insemination (IUI), using a volume of 0.5 ml of the inseminate, or Fallopian tube sperm perfusion (FSP), using a volume of 4 ml of inseminate. The protocols for ovarian stimulation and induction of ovulation were the same in the two groups. The two groups were similar concerning age of the female at the start of treatment and the number of follicles > 15 mm diameter, the serum oestradiol concentrations and the endometrial thickness on the day of human chorionic gonadotrophin (HCG) administration. The mean (+/- SD) number of motile spermatozoa inseminated was significantly higher in the FSP group than in the IUI group (52 +/- 5 x 10(6) and 28 +/- 3 x 10(6) respectively). In the FSP group, 30 women were given a total of 52 treatment cycles; 14 clinical pregnancies occurred in this group, giving a pregnancy rate of 26.9% per cycle and 46.7% per woman. In the IUI group, 28 women were given a total of 51 treatment cycles; five clinical pregnancies occurred, giving a pregnancy rate of 9.8% per cycle and 17.9% per woman. The pregnancy rates per cycle and per woman in the FSP group were significantly higher than in the IUI group (P < 0.05, chi-square test). This study indicates that in the treatment of couples with unexplained infertility, Fallopian tube sperm perfusion (FSP) is more successful than intra-uterine insemination (IUI).


Measurement and control practices in Finnish wastewater networks.
In this paper, we describe measurement and control practices in Finnish wastewater networks. We have surveyed the 14 largest wastewater treatment plants in the country, which account for approximately 40% of total Finnish treatment capacity. It was found that these plants still only rely on a few, traditional measurement techniques. The treatment processes could be improved, and the treatment could be made more energy-efficient by installing modern instrumentation. We review some recent developments in wastewater plant instrumentation technology and suggest improvements to Finnish plants.


Signature of Wave Chaos in Spectral Characteristics of Microcavity Lasers.
We report an experimental investigation on the spectra of fully chaotic and nonchaotic microcavity lasers under continuous-wave operating conditions. It is found that fully chaotic microcavity lasers operate in single mode, whereas nonchaotic microcavity lasers operate in multimode. The suppression of multimode lasing for fully chaotic microcavity lasers is explained by large spatial overlaps of the resonance wave functions that spread throughout the two-dimensional cavity due to the ergodicity of chaotic ray orbits.


Elaborate Design of d8-d10 Heteronuclear Phosphors for Ultrahigh-Efficiency Solution-Processed Organic Light-Emitting Diodes.
Highly soluble d8-d10 heteronuclear phosphors afford an alternative approach to achieve high-efficiency organic light-emitting diodes (OLEDs) through a solution process. In this work, four highly phosphorescent d8-d10 heteronuclear complexes with significant Pt-Au interactions were prepared. By judicious selection of sterically hindered and π-conjugated substituents in triphosphine ligands, the phosphorescence is dramatically promoted through effectively prohibiting nonradiative thermal relaxation with an efficiency of 0.94-0.99 in doping films. Exploiting highly emissive Pt-Au complexes as phosphorescent dopants, ultrahigh-efficiency solution-processed OLEDs were attained. The peak current efficiency, power efficiency, and external quantum efficiency are 96.2 cd A-1, 65.0 lm W-1, and 26.4% for the green-emitting PtAu2 phosphor and 68.6 cd A-1, 42.5 lm W-1, and 25.1% for the orange-emitting Pt2Au phosphor, which represent the state-of-art for solution-processed OLEDs based on non-iridium phosphors.


The Cross-sectional and Longitudinal Association Between Thyroid Function and Depression: A Population-Based Study.
An association of thyroid function with mood disorders has been widely suggested, but very few studies have examined this association longitudinally. We assessed the cross-sectional and longitudinal association between thyroid function and depression in a population-based cohort. 9,471 individuals were included in cross-sectional analyses, of whom 8,366 had longitudinal data. At baseline, we assessed thyroid function using serum samples (thyrotropin (TSH), free thyroxine (FT4) and thyroid peroxidase antibodies (TPOAb)) and depressive symptoms using the Centre for Epidemiologic Studies Depression (CES-D) scale. Incident depressive events (N = 1,366) were continuously followed-up with the CES-D and clinical interviews. We analysed the cross-sectional association of thyroid function and thyroid disease with depressive symptoms using linear and logistic regression, and the longitudinal association with cox proportional hazard models for depressive events. Lower TSH levels and lower and higher FT4 levels were cross-sectionally associated with more depressive symptoms with a B of -0.07 per one unit increase of natural log-transformed TSH (95% confidence interval -0.11; -0.04). Furthermore, hypothyroidism was cross-sectionally associated with less depressive symptoms and hyperthyroidism with more depressive symptoms. Longitudinally, there was a U-shaped association between FT4 and incident depressive events but only in euthyroid participants. We show a cross-sectional association between thyroid (dys-)function with depressive symptoms, and a U-shaped association between FT4 and incident depressive events in euthyroid individuals. Our findings suggest an association of thyroid function with the risk of developing depression, albeit small. Reverse causation and additional underlying factors may also contribute to the association.


Neurosurgical patients' perceptions of the "surgeon+": a qualitative study.
Neurosurgical patients bear a varying degree of anxiety when confronted with having to undergo surgery or even visit with a neurosurgeon in consultation. Previous studies have suggested that patient perceptions can heavily influence the patient-physician encounter. Accordingly, a better understanding of these perceptions can marshal our knowledge regarding strategies for improving patient-physician interactions during such an apprehensive time. The aim of the present study was to qualitatively examine patient values and preferences for a neurosurgeon who participates in extraclinical activities (i.e., a "neurosurgeon+") and understand the factors that influence these perceptions. Semistructured face-to-face interviews with 47 neurosurgical patients were conducted. Patients were recruited from the Toronto Western Hospital neurosurgery clinics for cranial and spinal conditions. Descriptive summary statistics were used to characterize the study participants. Family members were encouraged to contribute to the interviews. Interviews were audio-recorded, transcribed, and subjected to thematic analysis by using open and axial coding. Patients generally indicated that they want to feel confident in their neurosurgeon. A number of factors contribute to this confidence, including a strong positive referral from another physician. Patients are inclined to search for information pertaining to the qualifications of neurosurgeons online, and a perception of the neurosurgeon's adeptness given his or her qualifications is important for patients. Although there were some differences in patient values between those in the cranial and spinal groups, overall, neurosurgical patients tend to positively view their neurosurgeon's involvement in extraclinical duties. This study details the first comprehensive clinical qualitative study of patient perceptions of neurosurgeons and provides a descriptive framework for understanding patient values in this clinical domain.


Radioimmunodetection of human choriocarcinoma xenografts by monoclonal antibody to placental alkaline phosphatase.
Placental alkaline phosphatase (PLAP)-specific monoclonal antibody (MAb) 11-D-10, which did not react with other isoenzymes of alkaline phosphatase (AP), was raised by a hybridoma technique. MAb 11-D-10 was radiolabeled and administered to athymic mice bearing human choriocarcinoma containing PLAP. This antibody was found to be more specifically localized in tumor tissue as compared to normal tissues. The tissue-to-blood ratio (T/B ratio) of MAb 11-D-10 in tumor tissue increased from 1.38 at 2 days to 2.51 at 5 days after administration. On the other hand, the T/B ratios of isotype control non-immunized IgM in tumor tissue were 0.72 and 0.87 at 2 days and 5 days after administration, respectively. 131I-labeled MAb 11-D-10 was administered to athymic mice bearing choriocarcinomas of various sizes and various PLAP contents to examine the effect on the radioimage of the differences in tumor size and PLAP content. Tumors less than 0.3 cm in diameter could be imaged clearly by gamma-scintigraphy without blood pool image subtraction. The strength of the radioimage correlated fairly well with PLAP content.


[Accomplishments of tumor surgery in neuroblastoma in childhood].
Survival rates in patients with neuroblastoma did not significantly improve during the last two decades. This is particularly true for stage IV tumors. This stage seems to be a tumor fundamentally different from the more localized stages in its biological behavior, and it is not known, whether stage IV tumors originate from a localized stage by metastatic spread. Intensive investigations regarding new therapeutic approaches on an immunological basis or by stimulation of tumor maturation have been unsuccessful by now. Surgery in neuroblastoma has to be adapted to the particular stage to be treated. Certainly, surgery has to be incorporated into a therapeutic strategy which includes the whole spectrum of modern anticancer therapy. Such a therapeutic strategy will be provided by multicenter cooperative studies, such as the neuroblastoma study designed by the German Association of Paediatric Oncology (GPO). A treatment of neuroblastoma without incorporation in a multicenter cooperative study should not be accepted as modern standard.


α-Lipoic acid alleviates dextran sulfate sodium salt-induced ulcerative colitis via modulating the Keap1-Nrf2 signaling pathway and inhibiting ferroptosis.
Inflammatory bowel disease (IBD) is a chronically relapsing inflammatory disease with severe diarrhea, fatigue and weight loss. α-Lipoic acid (LA), a well-known antioxidant, is able to scavenge reactive oxygen species (ROS) and maintain a healthy cellular redox state. However, the role of LA in protecting IBD is still unclear. Hence the aim of this research was to investigate the protective effect of LA on dextran sulfate sodium salt-induced ulcerative colitis (UC) and its underlying mechanism. Here, our findings showed that LA significantly alleviated UC symptoms and the overproduction of pro-inflammatory cytokines in UC mice. In addition, LA treatment inhibited intestinal cell apoptosis by regulating the expression levels of p53/caspase-3 pathway-related protein in UC mice. Meanwhile, the inhibitory effects of LA on colonic oxidative stress and ferroptosis were revealed. Our study further demonstrated that LA treatment could regulate the Kelch-like ECH-associating protein 1 (Keap1)-nuclear factor E2-related factor 2 (Nrf2) signaling pathway. Interestingly, we confirmed that LA inhibited ferroptosis by attenuating endoplasmic reticulum stress and suppressing apoptosis in erastin-induced ferroptosis model in vitro. Taken together, this study's findings suggest that LA could be considered as a therapeutic agent protecting against IBD. © 2023 Society of Chemical Industry.


Endoscopic Diagnosis and Differentiation of Inflammatory Bowel Disease.
Patients with inflammatory bowel disease have significantly increased in recent decades in Korea. Intestinal tuberculosis (ITB) and intestinal Behcet's disease (BD), which should be differentiated from Crohn's disease (CD), are more frequent in Korea than in the West. Thus, the accurate diagnosis of these inflammatory diseases is problematic in Korea and clinicians should fully understand their clinical and endoscopic characteristics. Ulcerative colitis mostly presents with rectal inflammation and continuous lesions, while CD presents with discontinuous inflammatory lesions and frequently involves the ileocecal area. Involvement of fewer than four segments, a patulous ileocecal valve, transverse ulcers, and scars or pseudopolyps are more frequently seen in ITB than in CD. A few ulcers with discrete margins are a typical endoscopic finding of intestinal BD. However, the differential diagnosis is difficult in many clinical situations because typical endoscopic findings are not always observed. Therefore, clinicians should also consider symptoms and laboratory, pathological, and radiological findings, in addition to endoscopic findings.


Distribution and onset of retinaldehyde dehydrogenase (zRalDH) expression in zebra finch brain: lack of sex difference in HVC and RA at early posthatch ages.
Using in situ hybridization to detect the expression of the retinoic acid synthesizing enzyme (retinaldehyde dehydrogenase: zRalDH) mRNA, we mapped the distribution of its expression in adult zebra finch brain. In the neural song circuit, strong expression was found in high vocal center (HVC), para-HVC, and at a very low level in the robust nucleus of the arcopallium (RA). The expression in HVC and RA was found in both males and females. Outside of the song system, major areas of expression were in medial nidopallium (N), hyperpallium apicale (HA), mesopallium ventrale (MV), taenial amygdala (TnA), cerebellar Purkinje cells, and nucleus isthmo-opticus (IO). In nestlings, we found zRalDH mRNA expression in HVC and RA as early as posthatch day 4 or 5 (P4-5), although the expression varied among individuals. Thus, retinoic acid synthesis in HVC and RA could participate in song system formation and development. However, we found no sex difference in volume or intensity of zRalDH and androgen receptor (AR) expression in HVC and RA at P11 prior to the development of significant size dimorphisms in these nuclei. The size of HVC in females at P11 defined by zRalDH expression was greater than that in adult females, suggesting that HVC might experience net cell loss between P11 and adulthood.


[Early integration of palliative care in oncology].
Palliative care has evolved in the last half a century from a philosophy of care aiming at care of dying patients to specific/standalone medical specialization caring of patients with incurable diseases. Patients with advanced cancer suffer from physical and psychical symptoms, existential and social distress and have limited prognosis. Today we have strong clinical data about feasibility and usefulness of early integration of palliative care in oncology in terms of better quality of life, symptom control and survival. The question is not if, but when, whom and how is the best way to integrate palliative care into modern oncology. This article reviews data from clinical trials, presents models of cooperation for early integration and raises questions remained to be solved in a future.


Functional analysis of lipid metabolism genes in wine yeasts during alcoholic fermentation at low temperature.
Wine produced by low-temperature fermentation is mostly considered to have improved sensory qualities. However few commercial wine strains available on the market are well-adapted to ferment at low temperature (10 - 15°C). The lipid metabolism of Saccharomyces cerevisiae plays a central role in low temperature adaptation. One strategy to modify lipid composition is to alter transcriptional activity by deleting or overexpressing the key genes of lipid metabolism. In a previous study, we identified the genes of the phospholipid, sterol and sphingolipid pathways, which impacted on growth capacity at low temperature. In the present study, we aimed to determine the influence of these genes on fermentation performance and growth during low-temperature wine fermentations. We analyzed the phenotype during fermentation at the low and optimal temperature of the lipid mutant and overexpressing strains in the background of a derivative commercial wine strain. The increase in the gene dosage of some of these lipid genes, e.g., PSD1, LCB3, DPL1 and OLE1, improved fermentation activity during low-temperature fermentations, thus confirming their positive role during wine yeast adaptation to cold. Genes whose overexpression improved fermentation activity at 12°C were overexpressed by chromosomal integration into commercial wine yeast QA23. Fermentations in synthetic and natural grape must were carried out by this new set of overexpressing strains. The strains overexpressing OLE1 and DPL1 were able to finish fermentation before commercial wine yeast QA23. Only the OLE1 gene overexpression produced a specific aroma profile in the wines produced with natural grape must.


Application of CRISPR-Cas system in the diagnosis and therapy of ESKAPE infections.
Antimicrobial-resistant ESKAPE (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species) pathogens represent a global threat to human health. ESKAPE pathogens are the most common opportunistic pathogens in nosocomial infections, and a considerable number of their clinical isolates are not susceptible to conventional antimicrobial therapy. Therefore, innovative therapeutic strategies that can effectively deal with ESKAPE pathogens will bring huge social and economic benefits and ease the suffering of tens of thousands of patients. Among these strategies, CRISPR (clustered regularly interspaced short palindromic repeats) system has received extra attention due to its high specificity. Regrettably, there is currently no direct CRISPR-system-based anti-infective treatment. This paper reviews the applications of CRISPR-Cas system in the study of ESKAPE pathogens, aiming to provide directions for the research of ideal new drugs and provide a reference for solving a series of problems caused by multidrug-resistant bacteria (MDR) in the post-antibiotic era. However, most research is still far from clinical application.


The role of anxiety sensitivity in subjective and physiological responses to social and physical stressors.
This study examined the specificity of the relationship between anxiety sensitivity (AS), a measure of catastrophizing about arousal-related sensations, and pain responses, by examining the effect of AS on responses to stressors of a physical and social nature. Healthy men and women (n = 129) between the ages of 18 and 25 years were recruited from the community to participate in a study examining subjective, cognitive and behavioural responses to different types of stressors. Participants were randomly assigned to one of 3 groups: (i) a neutral condition in which they sat quietly and read a popular magazine; (ii) a social stress condition in which they anticipated having to give a self-disclosing speech; and (iii) a physical stress condition in which they were presented with 3 countdown to shock trials where a mild electrical shock was administered on the non-dominant arm. Subjective ratings and physiological responses were recorded in anticipation of the stressor and immediately after stress exposure. Results indicated that AS was indirectly related to pain ratings via its effect on anticipatory anxiety ratings. AS was associated with anticipatory anxiety ratings, regardless of whether the stressor was of a physical or social nature. Furthermore, AS was not shown to be directly associated with exaggerated subjective or physiological reactions to the physical stressor. These results indicate that the role of AS in pain responses may be mediated through a global effect on anxiety, and limited to the anticipatory stage of the pain experience. If future studies yield similar findings in pain patients, then they would suggest that interventions for helping individuals high in AS should focus on catastrophic thinking in anticipation of stressors in general, rather than on pain-specific stressors.


A network investigation on idiopathic hypogonadotropic hypogonadism in china.
Idiopathic hypogonadotropic hypogonadism (IHH) is a rare condition in which puberty does not take place naturally. We aimed to develop and follow an internet-based cohort and to improve our understanding of the disease. We established an internet-based questionnaire survey. A total of 74 male IHH patients were recruited from the Chinese largest IHH network social group. The clinical symptoms before treatment mainly included small testis, underdeveloped secondary sexual characteristics, and sexual dysfunction. After treatment, the penis length, testicular volume, external genital organ development, pubic hair, beard, laryngeal prominence, erection, and spermatorrhea were improved significantly (P < 0.001). 18.9% of the patients completed fertility; however, more than half of the patients still complained of poor happiness and low physical strength. In addition, improvements in penis and pubic hair development, testosterone normalization and the physical strength in IHH patients who received gonadotropin and androgen replacement therapy were better than in those who received single gonadotropin therapy (P < 0.05 for all). In conclusion, disease-specific network investigation can be used as an alternative method of medical research for rare diseases. The results of our cross-sectional study showed the effectiveness of hormone replacement therapy for IHH and implied that gonadotropin and androgen replacement therapy may be superior to gonadotropin treatment alone.


An evaluation of response prompts for teaching behavior chains.
Individuals who have been diagnosed with autism spectrum disorders can have difficulty acquiring new skills, and teaching procedures found to be efficient with 1 individual may not be efficient with others. However, relatively little research has evaluated methods to identify efficient, individualized response-prompt and prompt-fading procedures. We evaluated an assessment of multiple response prompts and prompt-fading procedures with 10 individuals with an autism spectrum disorder. The prompt types assessed were verbal and gestural, model, and physical. Prompt-fading procedures assessed were least to most, most to least, and a progressive delay. Each assessment was conducted at least twice, and the findings of both prompt-type and prompt-fading assessments were generally reliable. A final validity test showed the assessment outcomes to have generality that may extend to other clinically significant responses.


Is Substance Use a Team Sport? Attraction to Team, Perceived Norms, and Alcohol and Marijuana Use Among Male and Female Intercollegiate Athletes.
This research examined the role of attraction to one's team in predicting alcohol and marijuana use among intercollegiate athletes. Attraction to team and alcohol-related information were collected via an online survey and marijuana use-related information was gathered in a live setting. We investigated the influence of attraction to one's team above and beyond the influence of gender and perceived norms, and attraction to team as a moderator of these relationships. Attraction to one's team accounted for significant variance in marijuana use, and alcohol-related consequences after controlling for alcohol consumption. Regression analyses revealed significant interactions between gender, attraction to team, and norms in predicting alcohol and marijuana use. Stronger attraction to one's team may increase alcohol use but decrease marijuana use among male athletes, suggesting the importance of attraction to team when developing interventions for athletes.


Efflux pump inhibitors: targeting mycobacterial efflux systems to enhance TB therapy.
The emergence of drug resistance continues to plague TB control, with a global increase in the prevalence of MDR-TB. This acts as a gateway to XDR-TB and thus emphasizes the urgency for drug development and optimal treatment options. Bedaquiline is the first new anti-TB drug approved by the FDA in 40 years and has been shown to be an effective treatment option for MDR Mycobacterium tuberculosis infection. Bedaquiline has also recently been included in clinical trials for new regimens with the aim of improving and shortening treatment periods. Alarmingly, efflux-mediated bedaquiline resistance, as well as efflux-mediated cross-resistance to clofazimine, has been identified in treatment failures. This mechanism of resistance results in efflux of a variety of anti-TB drugs from the bacterial cell, thereby decreasing the intracellular drug concentration. In doing so, the bacillus is able to render the antibiotic treatment ineffective. Recent studies have explored strategies to reverse the resistance phenotype conferred by efflux pump activation. It was observed that the addition of efflux pump inhibitors partially restored drug susceptibility in vitro and in vivo. This has significant clinical implications, especially in MDR-TB management where treatment options are extremely limited. This review aims to highlight the current efflux pump inhibitors effective against M. tuberculosis, the effect of efflux pump inhibitors on mycobacterial growth and the clinical promise of treatment with efflux pump inhibitors and standard anti-TB therapy.


Maternal plasma biomarkers for down syndrome: present and future.
Down syndrome is the most common cause of mental retardation and has an incidence of between 1:600 and 1:800 pregnancies. It is the condition for which prenatal diagnosis is requested the most and most developed countries have adopted a screening program based around maternal plasma/serum testing and ultrasound. Advances have been made recently to eliminate invasive testing for genetic diagnosis of this condition based on the analysis of free fetal DNA in maternal plasma. But, routine noninvasive prenatal diagnosis for trisomy 21 still appears to be years away. Screening based on assessment of various biomarkers present in maternal plasma represents a front-line test to assess the risk of the mother carrying an aneuploid fetus. Recent comparative proteomics techniques have resulted in studies that have assessed maternal plasma from mothers carrying normal and trisomy 21 fetuses and various gestational ages. Over 100 biomarker candidates have been described, but little consensus has emerged. This may be due to a number of compounded factors, but interesting to note that other neurological disorders have overlapping biomarkers. This article describes these developments and how these biomarkers could contribute to future screening in an emerging era where next-generation sequencing of free fetal DNA will be established in prenatal diagnostics, which appears imminent.


Practical Considerations for the Use of Subcutaneous Treatment in the Management of Dyslipidaemia.
Suboptimal drug adherence represents a major challenge to effective primary and secondary prevention of cardiovascular disease. While adherence is influenced by multiple considerations, polypharmacy and dosing frequency appear to be rate-limiting factors in patient satisfaction and subsequent adherence. The cardiovascular and metabolic therapeutic areas have recently benefited from a number of advances in drug therapy, in particular protease proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors and incretin-based therapies, respectively. These drugs are administered subcutaneously and offer efficacious treatment options with reduced dosing frequency. Whilst patients with diabetes and diabetologists are well initiated to injectable therapies, the cardiovascular therapeutic arena has traditionally been dominated by oral agents. It is therefore important to examine the practical aspects of treating patients with these new lipid-lowering agents, to ensure they are optimally deployed in everyday clinical practice.


Cigarette smoking, oral hygiene and periodontal health in Swedish army conscripts.
Possible dissimilarities between smokers and nonsmokers regarding oral hygiene, gingivitis, periodontal pocketing and alveolar bone loss were studied in a sample of 134 army conscripts. Compared to nonsmokers, smokers had a higher plaque index and greater severity of gingivitis, while no differences were found concerning pocket depth and bone loss. It could be demonstrated that the difference regarding gingivitis disappeared when a check was made for plaque values. It still remains to be explained why plaque deposition is more pronounced in smokers.


Patient Controlled Epidural Labour Analgesia (PCEA): A Comparison Between Ropivacaine, Ropivacaine-Fentanyl and Ropivacaine-Clonidine.
Feeling of pain is one of the most important emotional determinants which dominate the perception of females who undergo the process of labour and delivery. Patient controlled epidural labour analgesia (PCEA) is convenient and safer technique for this purpose. Very few studies compared clonidine and fentanyl with ropivacaine in labour analgesia in past. This study was undertaken to compare fentanyl and clonidine in PCEA. To compare low concentration ropivacaine with or without fentanyl or clonidine for labour analgesia and its effect on maternal and foetal safety. Prospective, double blind, randomized, comparative study. Ninety primegravida in labour were divided into three groups (n=30) and patient controlled epidural labour analgesia was given to them: Initial bolus of 10ml of ropivacaine 0.125% in Group I; with fentanyl 2 μg/ml in Group II and with clonidine 1μg/kg in Group III. Subsequently each group received ropivacaine 0.125% through patient controlled epidural analgesia (PCEA) as background infusion of 5 ml/hr with lockout interval time of 10min and subsequent bolus of 5ml. Hemodynamic parameters, sensory level, motor block and pain relief were noted. Total analgesic dose of local anaesthetic and feto-maternal adverse effects were also recorded. At baseline, groups were matched demographically, hemodynamically as well as for intensity of pain. There was a statistically significant decrease in hemodynamic parameters from baseline in all groups with maximum reduction in group III. A significant difference among groups in VAS was observed at zero min and from 120min till 240min intervals and lowest values were in Group III. No significant difference was observed among the groups for mode of delivery and expulsive efforts. Total analgesic dose and PCA bolus requirement was maximum in Group I and minimum in Group III and the difference was statistically significant among groups. Six (20%) patients had shivering in Group II and hypotension was recorded in only 1 (3.3%) patient of Group III. Ropivacaine 0.125% was effective in decreasing labour pain without any motor blockade. Clonidine 1μg/kg was superior to fentanyl 2μg/ml as an adjuvant in PCEA for labour without any significant feto-maternal adverse effects.


Liver lesions and oral contraceptive steroids.
Two strains of mice, CF-LP and Swiss-Webster random-bred, were evaluated for liver neoplasia after administration of oral contraceptive steroids. No increased incidence of hepatocellular tumors was found beyond the variation expected by chance. The overall tumor incidence in treated and untreated groups was identical. No significant increase in tumor size was observed in the treated animals. Liver weights progressively increased in several of the treated groups. In both treated and untreated animals hepatocellular neoplasia was usually accompanied by intracytoplasmic inclusions similar to those observed in human liver tumors. Vascular lesions were observed in some of the animals receiving large doses of contraceptive steroids. While these may be the result of local toxicity, their similarity to lesions observed in benign liver tumors warrants further investigation. No evidence was found to suggest that contraceptive steroids act as initiators of liver neoplasia.


Preparation and anti-HIV activity of N-3-substituted thymidine nucleoside analogs.
A series of 22 derivatives of AZT substituted at the N-3 position of the thymine base were prepared and evaluated for anti-HIV activity in cell culture (Lai strain of HIV-1 in CEM-c113 cells). The AZT analogs bearing a N-3 amino group (7), a hydroxyalkyl chain (12f), and a phosphonomethyl (12k) substituent displayed activities in the 0.045-0.082 microM range. The analogs 12d, 12e, 12q, 15, and 19 were active at <0.5 microM concentration. Compound 18 in which two molecules of AZT are connected at N-3 via a two-carbon link and "dimer" 11 also displayed significant activity. To obtain information concerning the mechanism of RT inhibition by these AZT analogs, compounds 7, 12d, 12e, and 12q were incubated with recombinant HIV-1 RT in the presence of poly(A)-oligo[dT(12-18)] and poly(C)-oligo[dG(12-18)] template-primers. In contrast to AZT-TP (control), none of these nucleosides displayed any significant inhibition of RT in the recombinant enzyme assay, indicating that phosphorylation is a necessary prerequisite for activity.


A theoretical foundation for understanding clergy-perpetrated sexual abuse.
Incorporating elements from broadband theories of psychological adaptation to extreme adversity, including Summit's (1983) Child Sexual Abuse Accommodation Syndrome, Finkelhor and Browne's (1986) Traumagenic Dynamics Model of sexual abuse, and Pyszczynski and colleagues' (1997) Terror Management Theory, this paper proposes a unified theoretical model of clergy-perpetrated sexual abuse for future research. The model conceptualizes clergy-perpetrated sexual abuse as the convergence of interactive processes between the clergy-perpetrator, the parishioner-survivor, and the religious community.


CYP3A-mediated generation of aldehyde and hydrazine in atazanavir metabolism.
Atazanavir (ATV) is an antiretroviral drug of the protease inhibitor class. Multiple adverse effects of ATV have been reported in clinical practice, such as jaundice, nausea, abdominal pain, and headache. The exact mechanisms of ATV-related adverse effects are unknown. It is generally accepted that a predominant pathway of drug-induced toxicity is through the generation of reactive metabolites. Our current study was designed to explore reactive metabolites of ATV. We used a metabolomic approach to profile ATV metabolism in mice and human liver microsomes. We identified 5 known and 13 novel ATV metabolites. Three potential reactive metabolites were detected and characterized for the first time: one aromatic aldehyde, one α-hydroxyaldehyde, and one hydrazine. These potential reactive metabolites were primarily generated by CYP3A. Our results provide a clue for studies on ATV-related adverse effects from the aspect of metabolic activation. Further studies are suggested to illustrate the impact of these potential reactive metabolites on ATV-related adverse effects.


[Multifocal brain lesions].
Despite the current laboratory and instrumental approaches to the diagnosis, a patient with multiple brain lesions remains a difficult one. The reason is that these lesions can be caused by a variety of disorders, including rare ones and atypical forms. Distinguishing neoplastic lesions from non-neoplastic CNS disorders is crucial due to different treatment options. The authors report the case of a patient with multiple brain lesions, present a literature review of diseases to be differentially diagnosed with multifocal brain lesions and suggest a simple algorithm for the differential diagnosis. Timely clinical evaluation and a multidisciplinary approach are required for making a definitive diagnosis that is extremely important to start the appropriate therapy.


[Atrioventricular nodal reentrant tachycardia with 2:1 anterograde block].
We describe the case of a patient who presented with narrow QRS tachycardia at a rate of 100 b/min. The R-R intervals were constant, and negative P waves were evident in the inferior leads, midway between two ventricular complexes. A few minutes later, the tachycardia rate suddenly increased to 190 b/min, and the electrocardiographic pattern became typical of atrioventricular nodal reentrant tachycardia. Intravenous verapamil succeeded in restoring sinus rhythm. These data suggested an atrioventricular nodal reentrant tachycardia that at the beginning was associated with a 2:1 anterograde block.


Hypertrophy and transformation of muscle fibers in paraplegic patients.
Transcutaneous electrical stimulation of the quadriceps femoris muscle was applied in 14 paraplegic patients (10 spastic patients with spinal cord lesions and 4 patients with conus-cauda lesions with denervation atrophy). In both the spastic and the denervated group, the vastus lateralis muscle was biopsied and computed tomography (CT) images of the entire upper leg were made both at the onset and termination of the 8-month training period. The stimulation was carried out twice a day for 20 min. The increase in muscle tissue was significant in the CT images. The biopsies showed that the fiber diameter of both fiber types increased during the training period in the spastic group from 47 to 67 microns and in the denervated group from 22 to 38 microns. In both groups, the differences were significant between the first and second biopsies. Both groups showed a marked Type 2 fiber predominance. The histological and CT findings correlated with the clinical improvement of muscle function.


Peptidoglycan Association of Murein Lipoprotein Is Required for KpsD-Dependent Group 2 Capsular Polysaccharide Expression and Serum Resistance in a Uropathogenic Escherichia coli Isolate.
Murein lipoprotein (Lpp) and peptidoglycan-associated lipoprotein (Pal) are major outer membrane lipoproteins in Escherichia coli Their roles in cell-envelope integrity have been documented in E. coli laboratory strains, and while Lpp has been linked to serum resistance in vitro, the underlying mechanism has not been established. Here, lpp and pal mutants of uropathogenic E. coli strain CFT073 showed reduced survival in a mouse bacteremia model, but only the lpp mutant was sensitive to serum killing in vitro The peptidoglycan-bound Lpp form was specifically required for preventing complement-mediated bacterial lysis in vitro and complement-mediated clearance in vivo Compared to the wild-type strain, the lpp mutant had impaired K2 capsular polysaccharide production and was unable to respond to exposure to serum by elevating capsular polysaccharide amounts. These properties correlated with altered cellular distribution of KpsD, the predicted outer membrane translocon for "group 2" capsular polysaccharides. We identified a novel Lpp-dependent association between functional KpsD and peptidoglycan, highlighting important interplay between cell envelope components required for resistance to complement-mediated lysis in uropathogenic E. coli isolates.IMPORTANCE Uropathogenic E. coli (UPEC) isolates represent a significant cause of nosocomial urinary tract and bloodstream infections. Many UPEC isolates are resistant to serum killing. Here, we show that a major cell-envelope lipoprotein (murein lipoprotein) is required for serum resistance in vitro and for complement-mediated bacterial clearance in vivo This is mediated, in part, through a novel mechanism by which murein lipoprotein affects the proper assembly of a key component of the machinery involved in production of "group 2" capsules. The absence of murein lipoprotein results in impaired production of the capsule layer, a known participant in complement resistance. These results demonstrate an important role for murein lipoprotein in complex interactions between different outer membrane biogenesis pathways and further highlight the importance of lipoprotein assembly and transport in bacterial pathogenesis.