Preterm Premature Rupture of Membranes - Inpatient Versus Outpatient Management: an Evidence-Based Review.
According to current guidelines, inpatient management until birth is considered standard in pregnant women with preterm premature rupture of membranes (PPROM). With the increasing burden on obstetric departments and the growing importance of satisfaction and right to self-determination in pregnant women, outpatient management in PPROM is a possible alternative to inpatient monitoring. The most important criterion for this approach is to ensure the safety of both the mother and the child. Due to the small number of cases (n = 116), two randomised controlled trials (RCTs) comparing inpatient and outpatient management were unable to draw any conclusions. By 2020, eight retrospective comparative studies (cohort/observational studies) yielded the following outcomes: no significant differences in the rate of maternal complications (e.g., chorioamnionitis, premature placental abruption, umbilical cord prolapse) and in neonatal morbidity, significantly prolonged latency period with higher gestational age at birth, higher birth weight of neonates, and significantly shorter length of stay of preterm infants in neonatal intensive care, shorter hospital stay of pregnant women, and lower treatment costs with outpatient management. Concerns regarding this approach are mainly related to unpredictable complications with the need for rapid obstetric interventions, which cannot be performed in time in an outpatient setting. Prerequisites for outpatient management are the compliance of the expectant mother, the adherence to strict selection criteria and the assurance of adequate monitoring at home. Future research should aim at more accurate risk assessment of obstetric complications through studies with higher case numbers and standardisation of outpatient management under evidence-based criteria.


Involvement of phospholipase A2 and arachidonic acid in the depolarization-evoked accumulation of Ca2+ in hippocampal mossy fiber nerve endings.
Depolarization-evoked increases in intraterminal free Ca2+ are required for the induction of neurotransmitter release from nerve terminals. Although the mechanisms that regulate the voltage-induced accumulation of presynaptic Ca2+ remain obscure, there is evidence that the phospholipase-dependent accumulation of arachidonic acid, or its metabolites, may be involved. Therefore, fura-2 loaded hippocampal mossy fiber nerve endings were used to investigate the relationships between membrane depolarization, lipid metabolism and presynaptic Ca2+ availability. It was observed that depolarization of the nerve terminals with KCl induced an increase in intraterminal free calcium that was inhibited more than 90% by a combination of voltage-sensitive Ca2+ channel blockers. In addition, the K(+)-dependent effects on Ca2+ concentrations were attenuated in the presence of phospholipase A2 inhibitors, but were mimicked by the phospholipase A2 activator melittin and exogenous arachidonic acid. Both the melittin- and arachidonic acid-induced increases in presynaptic Ca2+ were reduced by voltage-sensitive Ca2+ channel blockers. The stimulatory effects of arachidonic acid appeared to be independent of its further metabolism to prostaglandins. In fact, inhibition of either cyclooxygenase or lipoxygenase pathways resulted in a potentiation of the depolarization-evoked increase in intraterminal free Ca2+. From these results, we propose that some portion of the depolarization-evoked increase in intraterminal free calcium depends on the activation of phospholipase A2 and the subsequent accumulation of unesterified arachidonic acid.


A transcriptome-based protein network that identifies new therapeutic targets in colorectal cancer.
Colon cancer occurrence is increasing worldwide, making it the third most frequent cancer. Although many therapeutic options are available and quite efficient at the early stages, survival is strongly decreased when the disease has spread to other organs. The identification of molecular markers of colon cancer is likely to help understanding its course and, eventually, to uncover novel genes to be targeted by drugs. In this study, we compared gene expression in a set of 95 human colon cancer samples to that in 19 normal colon mucosae, focusing on 401 genes from 5 selected pathways (Apoptosis, Cancer, Cholesterol metabolism and lipoprotein signaling, Drug metabolism, Wnt/beta-catenin). Deregulation of mRNA levels largely matched that of proteins, leading us to build in silico protein networks, starting from mRNA levels, to identify key proteins central to network activity. Among the analyzed genes, 10.5% (42) had no reported link with colon cancer, including the SFRP1, IGF1 and ADH1B (down), and MYC and IL8 (up), whose encoded proteins were most interacting with other proteins from the same or even distinct networks. Analyzing all pathways globally led us to uncover novel functional links between a priori unrelated or rather remotely connected pathways, such as the Drug metabolism and the Cancer pathways or, even more strikingly, between the Cholesterol metabolism and lipoprotein signaling and the Cancer pathways. In addition, we analyzed the responsiveness of some of the deregulated genes essential to network activities, to chemotherapeutic agents used alone or in presence of Lovastatin, a lipid-lowering drug. Some of these treatments could oppose the deregulations occurring in cancer samples, including those of the CHECK2, CYP51A1, HMGCS1, ITGA2, NME1 or VEGFA genes. Our network-based approach allowed discovering genes not previously known to play regulatory roles in colon cancer. Our results also showed that selected drug treatments might revert the cancer-specific deregulation of genes playing prominent roles within the networks operating to maintain colon homeostasis. Among those genes, some could constitute novel testable targets to eliminate colon cancer cells, either directly or, potentially, through the use of lipid-lowering drugs such as statins, in association with selected anticancer drugs.


Pinostilbene hydrate suppresses hepatic stellate cell activation via inhibition of miR-17-5p-mediated Wnt/β-catenin pathway.
In the development of liver fibrosis, activated hepatic stellate cells (HSCs) contribute to the synthesis and deposition of extracellular matrix (ECM) proteins. HSC activation is considered as a central driver of liver fibrosis. Recently, microRNAs (miRNAs) have been reported to act as key regulators in HSC activation. Pinostilbene hydrate (PSH), a methylated derivative of resveratrol, has demonstrated anti-inflammatory, antioxidant and anti-tumour activities. However, the effects of PSH on HSC activation remain unclear. The effects of PSH on HSC activation were examined. Moreover, the roles of WNT inhibitory factor 1 (WIF1) and miR-17-5p in the effects of PSH on HSC activation were examined. PSH induced a significant reduction in HSC proliferation. PSH also effectively inhibited HSC activation, with reduced α-SMA and collagen expression. Notably, it was found that Wnt/β-catenin signalling was involved in the effects of PSH on HSC activation. PSH resulted in Wnt/β-catenin signalling inactivation, with a reduction in TCF activity as well as β-catenin nuclear translocation. Further studies showed that PSH inhibited Wnt/β-catenin signalling via regulation of WIF1 and miR-17-5p. Reduced HSC activation caused by PSH could be restored by loss of WIF1 or miR-17-5p mimics. Luciferase reporter assays further confirmed that WIF1 was a target of miR-17-5p. PSH has a significant protective effect against HSC activation. In addition, we demonstrate that PSH enhances WIF1 expression and inhibits Wnt/β-catenin signalling via miR-17-5p, contributing to the suppression of HSC activation.


Early life-stage toxicity test for copper pyrithione and induction of skeletal anomaly in a teleost, the mummichog (Fundulus heteroclitus).
We used a teleost fish, the mummichog (Fundulus heteroclitus), to conduct early life-stage toxicity testing for copper pyrithione (CuPT). Fertilized mummichog eggs were exposed to CuPT at various concentrations for 50 d under continuous flow-through conditions. Hatchability, survival, growth, and morphologic abnormalities were measured. Hatchability did not differ significantly between any experimental group and control groups. Survival and growth were significantly reduced at 50 d in the groups exposed to 2 or 4 microg/L CuPT. During the test, morphologic abnormalities, such as vertebral deformity and formation of inflammatory masses in the lateral muscles, occurred in fish exposed to CuPT. Light and electron microscopic studies indicated that muscle dysfunction played a role in the vertebral deformity and revealed that the inflammatory mass was composed mainly of macrophages and necrotic myocytes. We consider that macrophages infiltrated and phagocytized necrotic cells, thus forming the inflammatory mass. In addition, acetylcholinesterase activity was markedly decreased in the 2- and 4-microg/L exposure groups, suggesting the skeletal deformity was due to mechanisms similar to those proposed for organophosphorous pesticide exposure.


RGD1564534 represses NLRP3 inflammasome activity in cerebral injury following ischemia-reperfusion by impairing miR-101a-3p-mediated Dusp1 inhibition.
Mitochondrial autophagy, the elimination of damaged mitochondria through autophagy, contributes to neuron survival in cerebral ischemia. Long non-coding RNAs (lncRNAs)/microRNAs (miRNAs)/mRNAs are important regulatory networks implicated in various biological processes, including cerebral ischemia-reperfusion (I/R) injury. Therefore, this work clarifies a novel RGD1564534-mediated regulatory network on mitochondrial autophagy in cerebral I/R injury. Differentially expressed lncRNAs in cerebral I/R injury were predicted by bioinformatics analysis. Expression of RGD1564534 was examined in the established middle cerebral artery occlusion (MCAO) rats and oxygen glucose deprivation/reoxygenation (OGD/R)-exposed neurons. We conducted luciferase activity, RNA pull-down and RIP assays to illustrate the interaction among RGD1564534, miR-101a-3p and Dusp1. Gain- or loss-of-function approaches were used to manipulate RGD1564534 and Dusp1 expression. The mechanism of RGD1564534 in cerebral I/R injury was evaluated both in vivo and in vitro. RGD1564534 was poorly expressed in the MCAO rats and OGD/R-treated cells, while its high expression attenuated nerve damage, cognitive dysfunction, brain white matter and small vessel damage in MCAO rats. In addition, RGD1564534 promoted mitochondrial autophagy and inhibited NLRP3 inflammasome activity. RGD1564534 competitively bound to miR-101a-3p and attenuated its binding to Dusp1, increasing the expression of Dusp1 in neurons. By this mechanism, RGD1564534 enhanced mitochondrial autophagy, reduced NLRP3 inflammasome activity and suppressed the neuron apoptosis induced by OGD/R. Altogether, RGD1564534 elevates the expression of Dusp1 by competitively binding to miR-101a-3p, which facilitates mitochondrial autophagy-mediated inactivation of NLRP3 inflammasome and thus retards cerebral I/R injury.


Immunogestosis: a new etiologic concept of "essential" EPH gestosis, with special consideration of the primigravid patient; preliminary report of a clinical study.
Evidence for immunologic processes taking part in the pathogenesis of what until now has been called the "essential" form of EPH gestosis is cited. The name of immunogestosis (IG) is introduced. The data of this preliminary study suggest that regular "inoculation" of the female genital tract with allogeneic spermatozoal histocompatibility antigens reduces the incidence of IG. Information about preconceptional sexual habits and contraceptive measures was obtained from 83 selected primigravid patients. Twenty-eight women had mild to moderate IG (Group B);55 did not (Group A). Women in Group B had had less contact with spermatozoa of partners than did women in Group A. Oral contraceptive consumption was less in Group B than in Group A. Women in Group B were younger than women in Group A. All these differences were statistically significant. A new immunoetiologic hypothesis referring to IG, as well as the theoretic and clinical implications arising from it, are discussed. This hypothesis is based on the assumption that spermatozoal histocompatibility antigens can either induce immunologic tolerance or be responsible for the phenomenon of immunologic enhancement in the maternal immunosystem. As the fetus inherits paternal histocompatibility antigens, it is concluded that pre-existing tolerance (or enhancement) exerts an IG-preventive function in a subsequent pregnancy.


Snoring and obstructive sleep apnea.
The most common form of sleep apnea is obstructive sleep apnea (OSA). It is characterized by the cessation of nasal airflow with persistence of ventilatory effort, as shown by paradoxical chest and abdominal movement, and varying degrees of oxygen desaturation. This article describes current methods of diagnosing OSA and available treatment for OSA and snoring.


Unusual HLA-B alleles in two tribes of Brazilian Indians.
The Kaingang and Guarani are culturally and linguistically distinct tribes of southern Brazil. Like all Amerindian groups they show limited HLA polymorphism, which probably reflects the small founder populations that colonized America by overland migration from Asia 11,000-40,000 years ago. We find the nucleotide sequences of HLA-B alleles from the Kaingang and Guarani to be distinct from those characterized in caucasian, oriental and other populations. By comparison, the HLA-A and C alleles are familiar. These results and those reported in the accompanying paper on the Waorani of Ecuador reveal that a marked evolution of HLA-B has occurred since humans first entered South America. New alleles have been formed through recombination between pre-existing alleles, not by point mutation, giving rise to distinctive diversification of HLA-B in different South American Indian tribes.


Integration of statistical shape modeling and alternating interpolation-based model tracking technique for measuring knee kinematics in vivo using clinical interleaved bi-plane fluoroscopy.
A 2D fluoroscopy/3D model-based registration with statistical shape modeling (SSM)-reconstructed subject-specific bone models will help reduce radiation exposure for 3D kinematic measurements of the knee using clinical alternating bi-plane fluoroscopy systems. The current study aimed to develop such an approach and evaluate in vivo its accuracy and identify the effects of the accuracy of SSM models on the kinematic measurements. An alternating interpolation-based model tracking (AIMT) approach with SSM-reconstructed subject-specific bone models was used for measuring 3D knee kinematics from dynamic alternating bi-plane fluoroscopy images. A two-phase optimization scheme was used to reconstruct subject-specific knee models from a CT-based SSM database of 60 knees using one, two, or three pairs of fluoroscopy images. Using the CT-reconstructed model as a benchmark, the performance of the AIMT with SSM-reconstructed models in measuring bone and joint kinematics during dynamic activity was evaluated in terms of mean target registration errors (mmTRE) for registered bone poses and the mean absolute differences (MAD) for each motion component of the joint poses. The mmTRE of the femur and tibia for one image pair were significantly greater than those for two and three image pairs without significant differences between two and three image pairs. The MAD was 1.16 to 1.22° for rotations and 1.18 to 1.22 mm for translations using one image pair. The corresponding values for two and three image pairs were 0.75 to 0.89° and 0.75 to 0.79 mm; and 0.57 to 0.79° and 0.6 to 0.69 mm, respectively. The MAD values for one image pair were significantly greater than those for two and three image pairs without significant differences between two and three image pairs. An AIMT approach with SSM-reconstructed models was developed, enabling the registration of interleaved fluoroscopy images and SSM-reconstructed models from more than one asynchronous fluoroscopy image pair. This new approach had sub-millimeter and sub-degree measurement accuracy when using more than one image pair, comparable to the accuracy of CT-based methods. This approach will be helpful for future kinematic measurements of the knee with reduced radiation exposure using 3D fluoroscopy with clinically alternating bi-plane fluoroscopy systems.


Phyto-interactive impact of green synthesized iron oxide nanoparticles and Rhizobium pusense on morpho-physiological and yield components of greengram.
The iron oxide nanoparticles (IONPs) prepared by green synthesis method using Syzigium cumini leaf extract was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The XRD confirmed the crystalline structure of green synthesized NPs measuring around 33 nm while SEM revealed its nearly spherical shape. Rhizobium species recovered from greengram nodules, identified by 16s rRNA gene sequencing as Rhizobium pusense produced 30% more exopolysaccharides (EPS) in basal medium treated with 1000 μg IONPs/ml. Compositional variation in EPS was observed by Fourier-transform infrared spectroscopy (FTIR). There was no reduction in rhizobial viability and no damage to bacterial membrane was observed under SEM and confocal laser scanning microscopy (CLSM), respectively. Effects of IONPs and R. pusense, used alone and in combination on the growth and development of greengram plants varied considerably. Plants grown with IONPs and R. pusence, used alone and in combination, showed a significant increase in seed germination rate, length and dry biomass of plant organs and seed components compared to controls. The IONPs in the presence of rhizobial strain further increased seed germination, plant growth, seed protein and pigments. Greater protein content (442 mg/g) was observed in seeds at 250 mg/kg of IONPs compared to control. Plants raised with mixture of IONPs plus R. pusense had maximum chlorophyll content (39.2 mg/g FW) while proline content decreased by 53% relative to controls. This study confirms that the green synthesis of IONPs from S. cumini leaf possess useful plant growth promoting effects and could be developed as a nano-biofertilizer for optimizing legume production.


Long-term Complications of Ebola Virus Disease: Prevalence and Predictors of Major Symptoms and the Role of Inflammation.
Cohort studies have reported a high prevalence of musculoskeletal, neurologic, auditory, and visual complications among Ebola virus disease (EVD) survivors. However, little is known about the host- and disease-related predictors of these symptoms and their etiological mechanisms. The presence and patterns of 8 cardinal symptoms that are most commonly reported following EVD survival were assessed in the 326 EVD survivors who participated in the ongoing longitudinal Liberian EVD Survivor Study. At quarterly study visits, symptoms that developed since acute EVD were recorded and blood was collected for biomarkers of inflammation and immune activation. At baseline (mean 408 days from acute EVD), 75.5% of survivors reported at least 1 new cardinal symptom since surviving EVD, which in 85.8% was rated as highly interfering with life. Two or more incident symptoms were reported by 61.0% of survivors, with pairings of joint pain, headache, or fatigue the most frequent. Women were significantly more likely than men to report headache, while older age was significantly associated with musculoskeletal and visual symptoms. In analyses adjusted for multiple comparisons, no statistically significant association was found between any symptom and 26 markers of inflammation and immune activation. Symptom frequency remained largely unchanged during study follow-up. Post-EVD complications occur in a majority of survivors and remain present more than 4 years after acute infection. An association between markers of inflammation and immune activation and individual symptoms was not found, suggesting an alternative etiology for persistent post-EVD symptomatology.


The heuristics of nurse responsiveness to critical patient monitor and ventilator alarms in a private room neonatal intensive care unit.
Alarm fatigue is a well-recognized patient safety concern in intensive care settings. Decreased nurse responsiveness and slow response times to alarms are the potentially dangerous consequences of alarm fatigue. The aim of this study was to determine the factors that modulate nurse responsiveness to critical patient monitor and ventilator alarms in the context of a private room neonatal intensive care setting. The study design comprised of both a questionnaire and video monitoring of nurse-responsiveness to critical alarms. The Likert scale questionnaire, comprising of 50 questions across thematic clusters (critical alarms, yellow alarms, perception, design, nursing action, and context) was administered to 56 nurses (90% response rate). Nearly 6000 critical alarms were recorded from 10 infants in approximately 2400 hours of video monitoring. Logistic regression was used to identify patient and alarm-level factors that modulate nurse-responsiveness to critical alarms, with a response being defined as a nurse entering the patient's room within the 90s of the alarm being generated. Based on the questionnaire, the majority of nurses found critical alarms to be clinically relevant even though the alarms did not always mandate clinical action. Based on video observations, for a median of 34% (IQR, 20-52) of critical alarms, the nurse was already present in the room. For the remaining alarms, the response rate within 90s was 26%. The median response time was 55s (IQR, 37-70s). Desaturation alarms were the most prevalent and accounted for more than 50% of all alarms. The odds of responding to bradycardia alarms, compared to desaturation alarms, were 1.47 (95% CI = 1.21-1.78; <0.001) while that of responding to a ventilator alarm was lower at 0.35 (95% CI = 0.27-0.46; p <0.001). For every 20s increase in the duration of an alarm, the odds of responding to the alarm (within 90s) increased to 1.15 (95% CI = 1.1-1.2; p <0.001). The random effect per infant improved the fit of the model to the data with the response times being slower for infants suffering from chronic illnesses while being faster for infants who were clinically unstable. Even though nurses respond to only a fraction of all critical alarms, they consider the vast majority of critical and yellow alarms as useful and relevant. When notified of a critical alarm, they seek waveform information and employ heuristics in determining whether or not to respond to the alarm. Amongst other factors, the category and duration of critical alarms along with the clinical status of the patient determine nurse-responsiveness to alarms.


Effects of capacitive and resistive electric transfer therapy in patients with painful shoulder impingement syndrome: a comparative study.
Capacitive and resistive electric transfer therapy (CARE) reduces pain and improves quality of life for many orthopaedic degenerative and inflammatory disorders. The research aim was to determine the effects of CARE on painful shoulder. The outcomes were pain reduction and recovery of shoulder function. A retrospective, observational case-control study was conducted. Participants were 46 patients (22 in the CARE group and 24 in the SHAM group). Clinical data, pain (visual analogic scale, VAS) and functional scale scores (Disabilities of the Arm, Shoulder and Hand scale, and Constant-Murley Scale) were measured at baseline T0 (before treatment), T1 (after treatment) and follow-up T2 (2 months after the end of the treatment). VAS scores in the CARE group improved from 7.23 ± 1.11 at baseline to 2.68 ± 0.99 at follow-up. The SHAM group did not experience any improvement. Similarly, functional scale scores improved in the CARE group compared with the SHAM group. Considering the small number of sessions needed, low cost and long-term benefits, CARE could be a useful therapeutic option for the conservative management of shoulder pain to restore pain-free and powerful movement to the shoulder joint.


In vitro modification of substituted cysteines as tool to study receptor functionality and structure-activity relationships.
Mutagenic investigations of expressed membrane proteins are routine, but the variety of modifications is limited by the twenty canonical amino acids. We describe an easy and effective cysteine substitution mutagenesis method to modify and investigate distinct amino acids in vitro. The approach combines the substituted cysteine accessibility method (SCAM) with a functional signal transduction readout system using different thiol-specific reagents. We applied this approach to the prolactin-releasing peptide receptor (PrRPR) to facilitate biochemical structure-activity relationship studies of eight crucial positions. Especially for D(6.59)C, the treatment with the positively charged methanethiosulfonate (MTS) ethylammonium led to an induced basal activity, whereas the coupling of the negatively charged MTS ethylsulfonate nearly reconstituted full activity, obviously by mimicking the wild-type charged side chain. At E(5.26)C, W(5.28)C, Y(5.38)C, and Q(7.35)C, accessibility was observed but hindered transfer into the active receptor conformation. Accordingly, the combination of SCAM and signaling assay is feasible and can be adapted to other G-protein-coupled receptors (GPCRs). This method circumvents the laborious way of inserting non-proteinogenic amino acids to investigate activity and ligand binding, with rising numbers of MTS reagents allowing selective side chain modification. This method pinpoints to residues being accessible but also presents potential molecular positions to investigate the global conformation.


In vitro induction of swine peripheral blood monocyte proliferation by the fibroblast-derived murine hematopoietic growth factor CSF-1.
The addition of conditioned medium from murine L929 fibroblasts (MGF) to cultures of swine peripheral blood mononuclear cells (MNL) resulted in growth of cells of macrophage/monocyte lineage (MO). Glass-adherent swine MNL, shown to be greater than 95% phagocytic MO, grew in the presence of MGF, whereas swine blood granulocytes and lymphocytes were not MGF-responsive. Primary and secondary MO growth were directly dependent on MGF presence and concentration. MGF-stimulated MO synthesized DNA, as measured by cellular incorporation of tritium-labeled thymidine (3H-TdR). This mitogenic response was maximal by 5 to 6 days in primary MO cultures and declined thereafter to a lower magnitude in secondary MO cultures. In the presence of MGF, viable MO numbers increased with an approximate population doubling time of 5 to 7 days in primary culture. This growth rate was prolonged, to about 10 to 12 days, for MGF-stimulated MO in secondary cultures. MGF removal from primary and secondary MO cultures resulted in rapid growth cessation and cell death. MGF-stimulated MO could not be sustained in secondary culture beyond 7 weeks. MGF-cultured MO were positive for latex phagocytosis, non-specific esterase, Fc-receptor expression, and could mediate antibody-dependent cell-mediated cytotoxicity. The MO-mitogenic principle of MGF was identified as the murine, macrophage-specific colony-stimulating factor, CSF-1 (M-CSF). The swine MO-proliferative response to MGF was inhibited by addition of monospecific goat antisera to M-CSF. Purified M-CSF stimulated the growth of swine MO from cultures of MNL and primary glass-adherent MO.


Preoperative hypoalbuminemia is an independent risk factor for conversion from laparoscopic to open cholecystectomy in patients with cholecystolithiasis.
Laparoscopic cholecystectomy (LC) is regarded as the first choice for patients with cholecystolithiasis, but some patients require conversion to open cholecystectomy (OC) because of inflammation-related incidents. Therefore, the aim of this study is to explore the risk factors for conversion to OC in patients undergoing elective LC for cholecystolithiasis. This study included 461 patients who underwent elective LC for cholecystolithiasis were between April 2000 and September 2010. Receiver-operator curve (ROC) analysis was used to define the ideal cut-off values of clinicolaboratory characteristics, and the area under the ROC for conversion was also measured. Univariate and multivariate analyses using preoperative clinicolaboratory characteristics were performed to investigate the most significant risk factors for conversion to OC in patients with cholecystolithiasis. Multivariate analysis using nine parameters selected by univariate analyses demonstrated that γ-glutamyltransferase (<20/>20 IU/L) (odds ratio, 8.777; 95% confidence interval, 1.132-68.06; P = 0.038), albumin (<3.8/>3.8 g/dL) (odds ratio, 0.329; 95% confidence interval, 0.127-0.850; P = 0.022), and platelet count (<27/>27 × 104 /mm3 ) (odds ratio, 2.573; 95% confidence interval, 1.048-6.319; P = 0.039) were associated with conversion. Among these three parameters, ROC curve analysis disclosed that albumin (0.705) had the largest area under the ROC (γ-glutamyltransferase, 0.622, platelet count, 0.536) for conversion. Preoperative hypoalbuminemia is the most important risk factor for conversion to OC in patients undergoing elective LC for cholecystolithiasis.


Evolution of HIV resistance during treatment interruption in experienced patients and after restarting a new therapy.
To analyse the evolution of resistance patterns in patients undergoing treatment interruption (TI) and re-initiating highly active anti-retroviral therapy (HAART). HIV-RT and -PR gene-sequences were analysed in 14 patients (>5 failing prior drugs) before and during TI and under a new HAART. Genotypes were interpreted using two bioinformatics systems. Additionally, virus load (VL) and CD4(+)-T-cell counts were measured. Six patients (42%) achieved sustained undetectable VL up to one year after TI (responders), while 8 (57%) maintained VL of more than 2,000 copies/mL (non-responders). Different patterns of resistance-mutations evolution were detected. During TI loss of all mutations was observed in three patients, a reduction of mutations was detected in seven patients, and no alteration was seen in four patients. In the responders, 87.5% of protease inhibitor (PI)-resistance mutations waned during TI and remained undetectable under the new treatment. In contrast, in the non-responder group most PI-resistance mutations continued noticeable under the new therapy. Loss of primary PI-resistance mutations and the presence of one fully active PI in the new regimen significantly correlated with success of subsequent treatment (p=0.028). In two patients new reverse transcriptase associated mutations were detected during TI, G190A (NNRTI mutation) and K70R (NRTI mutation). Appearance of K70R could be explained by a reverse direction of a previously described pathway of thymidin analogues mutation resistance development, while G190A could be due to prolonged subinhibitory drug levels after cessation of NNRTIs. In the evolution of HAART-resistance, different patterns were observed in responders and non-responders during but not before TI. Absence of PI-resistance associated mutations during and after TI and administration of a predicted fully active PI for the new therapy correlated with success. Newly detected mutations during TI may indicate reversibility of previously described mutational pathways.


Core directed self-assemblies in the solid state of retro Aib bis-peptide dicarboxylic acids; a design strategy for control of molecular orientation in peptides.
Self-assembly patterns as a function of the central core insert in the retro bis-peptide dicarboxylic acids HO-Aib-X-Aib-OH, containing oxalyl (-CO-CO-; 1), fumaryl (-CO-CH = CH-CO-; 2), and adipoyl [-CO-(CH2)4-CO-; 3], have been characterized by single crystal x-ray diffraction analyses. Extensive hydrogen bonding occurs in each crystal but there are no OH ... O binds between acid groups. Only two types of hydrogen bonds occur in all the crystals: NH ... O (acid terminal), 2.84-2.98 A and OH (acid terminal) ... O (core carbonyl), 2.55-2.67 A (except for an additional intramolecular C5 type bond in the oxalyl moiety in 1). The self-assembly patterns are a beta-network in 1, separate layer assemblies (beta-networks) for two independent molecules in 2 that combine into a three-dimensional gamma network, and separate ribbon assembles (alpha networks) for two independent molecules in 3 that combine into an extended beta-network sheet with hydrophobic faces.


The effects of cultural values on mental health among the Taiwanese people: mediating of attitudes toward emotional expression.
Empirical evidence has demonstrated that an individual's cultural values can influence his or her mental health. This study extends previous research by proposing and testing a model that examines mediating processes underlying the relationship between individuals' cultural values and their mental health. This 2-stage study used data collected from 208 (at time 1) and 159 (at time 2) full-time staff employed by private enterprises in Taiwan. The author tested hypotheses through the use of hierarchical multiple regression. The results showed that under horizontal individualism and vertical collectivism, the predictors of negative mental health (ie, somatic symptoms, anxiety and insomnia, social dysfunction and/or severe depression) were partially and almost completely achieved through the mediating effect of the negative attitudes toward emotional expression.


Patient perceptions of cardiovascular risk, lipid management and statins in type 1 diabetes.
Lipid-lowering reduces cardiovascular risk in type 1 diabetes (T1D), but dyslipidaemia remains under-recognised and under-treated. Through patient surveys, barriers to lipid management in T1D were identified, including lack of awareness of cardiovascular risk and cholesterol levels, preference for managing glycaemia over lipids, preference for lifestyle modification over pharmacotherapy, and statin side-effect concerns.


USP10 deubiquitinates Tau, mediating its aggregation.
Normal Tau promotes the assembly and stabilization of microtubules, thus, maintaining axon transport. In Alzheimer's disease (AD), Tau aggregation causes it to lose these above-mentioned functions. However, the molecular mechanism leading to Tau aggregation in AD remains ambiguous. Here, we report that USP10, one of the important deubiquitinases (DUBs), is involved in Tau aggregation. We found that USP10 is upregulated in postmortem human AD and APP/PS1 mice brains, but not in P301S mice brains. Moreover, in primary neuronal cultures, Aβ42 induces a dose-dependent USP10 upregulation, an increase in the levels of both total and phosphorylated Tau, as well as a markedly elevated Tau binding with USP10, that is accompanied by a significantly decreased Tau ubiquitination. In addition, overexpression of USP10 directly causes an increase in the levels of total and phosphorylated Tau, induces Tau aggregation, and delays in Tau degradation. Results from mass spectrometry, reciprocal immunoprecipitation, and immunofluorescence assays strongly prove Tau's interaction with USP10. This is further supported by the Tau307-326K and Tau341-378K peptides' competitive inhibition of Tau binding with USP10, attenuating Tau hyperphosphorylation and Tau deubiquitination. Together, our data strongly indicate that USP10 plays a critical role in mediating Tau aggregation via downregulating its ubiquitination and thus slowing down Tau turnover. Inhibition of USP10-Tau interaction might be therapeutically useful in the management of AD and related tauopathies.


Effect of boron nitride overlayers on Co@BNNSs/BN-Catalyzed aqueous phase selective hydrogenation of cinnamaldehyde.
The confinement effect known as efficient strategy to enhance the heterocatalytic activity and stability, but a clear view regarding the role of encapsulated overlayers is far from convincing at present, especially, the penetration of substrates with different size. Herein, the experimental evidence about the impacts of BN overlayers on hydrogenation is obtained over Co@BN/BN model catalysts with tuned thinness, in which BN overlayers encapsuled Co particles that dispersed on the defective BN supports, fabricating by the nitridizing of ball-milled BN microplates under NH3 atmosphere. The thinness and crystallinity of BN shells was simply tuned by controlling the pyrolyzed temperature (600-900 °C). The cinnamaldehyde (CAL) selective hydrogenation is taken as probe reaction due to (1) both larger CAL and small H2 molecule involved simultaneously, (2) the middle CC and terminal CO bonds all involved. Combined with structural analysis, the results demonstrate that small H2 molecule can penetrate into the metal-cover interface through the defect sites, then inner Co core dissociate it to atomic H, and the hydrogenation mainly resulting from the spillover of H atoms which occurred on the BN surface. As a result, the thickest BN shells (∼3.4 nm) with ordered-layer-lattice significantly hindered the adsorption and activation of CAL, also the longest H spillover distance led to the lowest activity of Co@BN/BN-900. Instead, Co@BN/BN-600 with merely 2 ∼ 3 overlayers presented the most efficient and highly chemoselective hydrogenation activity. The ultrathin but turbostratic BN overlayers provide more migrating sites also shortened the H spillover distance effectively, and the more favorable CO hydrogenation was also achieved driven by the steric hindrance effect of thinner BN shells. These observations provide new insights towards understanding of confined effect on catalysis process through the accurate regulation of BN shells properties.


Carcinoma oesophagus in a 14 year old child: report of a case and review of literature.
A 14 year old boy with well differentiated squamous cell carcinoma of the upper oesophagus is being presented because of its rarity. The patient presented with dysphagia for 8 months. Barium swallow and endoscopy revealed a narrowing in the upper oesophagus with a proximal dilatation diverticulum. No definite aetiologic factor could be demonstrated. The case was treated with definitive irradiation with excellent immediate response.


Pilot evaluation of a standardized patient actor training intervention to improve HIV care for adolescents and young adults in Kenya.
Poor retention in HIV care remains a major problem for Adolescents and Young Adults (AYA). A Standardized Patient (SP) clinical training intervention was developed to improve healthcare worker (HCW) "adolescent-friendly" competencies in Kenya. Professional actors were trained to portray HIV-infected AYA according to standardized scripts. HCWs completed a 2-day SP training that included didactic sessions, 7 video-recorded SP encounters, and group debriefing. AYA health experts rated HCWs by reviewing the video recordings. All HCWs (10/10) reported high satisfaction with the intervention and overall improvement in self-rated competency in caring for HIV-infected AYA. Cases were reported to be realistic and relevant by between 7 and 10 of 10 HCWs. The case on disclosure and adherence was rated as most challenging in communication and making medical decisions by HCWs. Areas identified by SPs for improvement by HCWs included allowing patients time to ask questions, and enabling SP to share sensitive information. The overall ICC by experts was low 0.27 (95% CI: -0.79 to 0.95), however, ICCs in assessment of HIV disclosure 0.78 (95% CI: 0.17-0.98), and sexual behavior 0.97 (95% CI: 0.89-0.99) were high. This intervention was acceptable for Kenyan HCWs and improved self-rated competency in caring for HIV-infected AYA.


Pericardial tamponade secondary to central venous catheterization and hyperalimentation in a very low birthweight infant.
A very low birthweight infant developed pericardial tamponade secondary to leakage of fat emulsion through a catheter lodged in the right atrial appendage. At autopsy examination a thrombus was lodged in the appendage, which presumably resulted in immobilization of the catheter and leakage of the fluid through an attenuated and necrotic myocardial wall.


Single modified cilia displayed by cells of human internal stratified epithelia (oral cavity, vagina).
Serial sections of human vaginal and keratinized oral-gingival epithelia were investigated for ciliary structures. Most melanocytes of the gingival epithelium lacked cilia, whereas almost all basal keratinocytes of the deeper portion of the epithelial ridges possessed one cilium each. In the suprabasal layers of the ridges only a few keratinocytes exhibited a single cilium. In the basal layer, at the top of the connective tissue papillae, approximately every second keratinocyte displayed a single cilium. In the suprabasal layers above the ridges no ciliated keratinocytes were observed. The basal cells of the vaginal epithelium were endowed with cilia, while cilia were absent from the suprabasal cells. In the human forearm epidermis most melanocytes and keratinocytes are supplied with a single cilium; it has been suggested that they may play a role in light reception. However, the widespread occurrence of 9 + 0 cilia in epithelial cells of internal epithelia and their coincidence with the sites of renewal of keratinocytes suggests that a relationship may exist between solitary cilia and mitotic activity.


Confocal Scanning Laser Ophthalmoscopy to Image Retinal Ganglion Cells in Real-Time.
Real-time imaging of retinal ganglion cells (RGCs) provides an opportunity for detailed investigation of retinal development, disease mechanisms, and the evaluation of interventions affecting ocular structures. Here we use a transgenic model to describe a step-by-step protocol for visualizing RGC survival in real-time by using confocal scanning laser ophthalmoscopy (cSLO).


Behavioural and psychological patterns of patients with idiopathic pulmonary fibrosis: a prospective study.
Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung condition. Currently, care models predominantly focus on acute medical and pharmacological needs. As a step towards holistic care, the aim of this prospective study was to investigate the psychological and behavioural needs of IPF patients treated with pirfenidone from diagnosis until two years of follow-up. The following variables were selected from the literature on patients' needs and the COM-B model, a theoretical model explaining behaviour: medication adherence, barriers to adherence, importance and intentions of medication adherence, anxiety, depression, health literacy, knowledge, reported side effects, adherence to sun protection recommendations, alcohol use, physical activity, quality of life and health status. Linear and generalised linear models for longitudinal data were used to evaluate the evolution since treatment initiation. We included 66 outpatients: 72.7% men, mean age of 70.3 years (range 50-87), predicted mean forced vital capacity of 85.8% (SD 17.4) and predicted mean diffusing capacity for monoxide of 56.9% (SD 15.7). The participants placed considerable importance on following the treatment recommendations. We noticed difficulties regarding health literacy, alcohol use, pirfenidone adherence (decline over time) and adherence to sun protection recommendations (early in follow-up care). There were low levels of physical activity (no effect of time), high body mass indices (decline over time) and moderate levels of depression and anxiety. When providing care to IPF patients, behavioural issues, health literacy and psychological well-being should be taken into consideration. There is a need to further explore interventions and care models to tackle these difficulties. Trial registration This study was registered in the ClinicalTrials.gov database (identifier NCT03567785) on May 9th, 2018.


Nocifensive behavior-related laser heat-evoked component in the rostral agranular insular cortex revealed using morphine analgesia.
The rostral agranular insular cortex (RAIC), an opioid-responsive site, is essential for modulating nociception in rats. Our previous studies have shown that morphine suppressed long latency laser heat-evoked nociceptive responses in the primary somatosensory cortex (SmI). By contrast, morphine significantly attenuated both short and long latency responses in the anterior cingulate cortex (ACC). The present study assessed the effect of morphine on laser heat-evoked responses in the RAIC. Laser heat irradiation applied to the rat forepaws at graded levels was used as a specific noxious stimulus. In the RAIC, the first part of the long latency component (140-250ms) of the laser heat-evoked response was enhanced by intraperitoneal morphine (5mg/kg). When the laser heat-evoked cortical responses were examined for trials showing strong nocifensive movement (paw licking), moderate nocifensive movement (paw lifting), and no nocifensive movement, a 140-250ms period enhancement was observed in the RAIC only for the paw lifting movement. This enhancement was absent in the SmI. Thus, our data suggest that the RAIC has a pain-related behavior-dependent neuronal component. Furthermore, the RAIC, ACC, and SmI are differentially modulated by morphine analgesia.


Quantitation of heat-shock proteins in clinical samples using mass spectrometry.
Mass spectrometry (MS) is a powerful analytical tool for proteomics research and drug and biomarker discovery. MS enables identification and quantification of known and unknown compounds by revealing their structural and chemical properties. Proper sample preparation for MS-based analysis is a critical step in the proteomics workflow because the quality and reproducibility of sample extraction and preparation for downstream analysis significantly impact the separation and identification capabilities of mass spectrometers. The highly expressed proteins represent potential biomarkers that could aid in diagnosis, therapy, or drug development. Because the proteome is so complex, there is no one standard method for preparing protein samples for MS analysis. Protocols differ depending on the type of sample, source, experiment, and method of analysis. Molecular chaperones play significant roles in almost all biological functions due to their capacity for detecting intracellular denatured/unfolded proteins, initiating refolding or denaturation of such malfolded protein sequences and more recently for their role in the extracellular milieu as chaperokines. In this chapter, we describe the latest techniques for quantitating the expression of molecular chaperones in human clinical samples.


Domestic flow of e-waste in São Paulo, Brazil: Characterization to support public policies.
Understanding the domestic flow of e-waste is essential for efficient waste management in urban contexts. However, diagnosis of domestic e-waste flow is complex due to its diffuse generation and dependence on consumer behavior. Here, we characterized domestic e-waste flow in São Paulo, Brazil (a megacity with roughly 11 million inhabitants in 3.5 million households), describing the stages of product acquisition, out-of-use storage, and end-of-life destination, via a population-based cross-sectional study using a statistically representative sample. We conducted household interviews using a structured questionnaire, with questions on characteristics, quantities, and behaviors of acquisition, replacement, storage, repair, and destination for 26 electric and electronic equipment (EEE) categories. Each household had on average 21 EEE (95% confidence interval [CI]: 19.7-21.7), of which 18 were in use and 3 were out-of-use. Out-of-use storage was common, occurring in 72.6% of households. Discarded EEE (i.e., e-waste) was destined for intended reuse (59.5%; 95% CI: 57.4-61.5%), recycling (20.4%; 95% CI: 18.8-22.1%), and, particularly for small EEE, municipal waste (16.0%; 95% CI: 14.5-17.6%). Other aspects of domestic e-waste flow (e.g., place and time of acquisition, second-hand acquisition, donation, intention to repair damaged EEE, and storage) were quantified and related to actions for public policies. This research shows that household surveys are useful for obtaining primary data to verify consumer behavior toward EEE. We expect the findings of this study to support decision-making for public policies related to e-waste management, particularly in countries where reverse logistics systems are in the initial phase of implementation.


Improved 30 day heart failure rehospitalization prediction through the addition of device-measured parameters.
This study aimed to improve in-person clinical evaluation on the day of heart failure (HF) hospitalization discharge by adding device-measured parameters to predict 30 day HF rehospitalization risk in cardiac resynchronization therapy-defibrillator (CRT-D) patients. In a cohort of Medicare patients with CRT-Ds, the independent prognostic value of four device-measured parameters was assessed relative to typical clinical parameters associated with rehospitalization risk. Medicare registry, claims, and Medtronic CareLink® Network data for these patients were analysed using logistic regression modelling and net reclassification methods. Among 1563 CRT-D patients, 411 patients had 607 HF hospitalization events during a median 6.3 years of follow-up. Compared with clinical variables alone, impedance measurements resulted in a 28% improvement between the predicted probabilities of having vs. not having a 30 day HF rehospitalization (relative integrated discrimination improvement = 0.28) and a net 42% improvement in the classification of 30 day HF rehospitalization events and non-events after an index HF hospitalization (net reclassification index = 0.42; 95% CI: 0.10, 0.74). In CRT patients, intrathoracic impedance measurements improve prediction of 30 day HF rehospitalization over clinical characteristics alone. The present study provides supportive data for the routine evaluation of intrathoracic impedance prior to discharge in patient with CRT devices. Furthermore, the models developed in this study could be used to design interventions to improve compliance with Medicare reimbursement guidelines regarding 30 day HF rehospitalization.


Varenicline and cytisine diminish the dysphoric-like state associated with spontaneous nicotine withdrawal in rats.
Tobacco addiction is characterized by a negative mood state upon smoking cessation and relapse after periods of abstinence. Clinical studies indicate that negative mood states lead to craving and relapse. The partial α4/α6/β2* nicotinic acetylcholine receptor (nAChR) agonists varenicline and cytisine are widely used as smoking cessation treatments. Varenicline has been approved in the United States for smoking cessation and cytisine is used in Eastern European countries. Despite the widespread use of these compounds, very little is known about their effects on mood states. These studies investigated the effects of varenicline, cytisine, and the cytisine-derivative 3-(pyridin-3'-yl)-cytisine (3-pyr-Cyt) on brain reward function in nicotine-naive and nicotine-withdrawing rats. The cytisine-derivative 3-pyr-Cyt is a very weak α4β2* nAChR partial agonist and like cytisine and varenicline has antidepressant-like effects in animal models. The intracranial self-stimulation (ICSS) procedure was used to investigate the effects of these compounds on brain reward function. Elevations in ICSS thresholds reflect a dysphoric state and a lowering of thresholds is indicative of a potentiation of brain reward function. It was shown that acute administration of nicotine and varenicline lowered ICSS thresholds. Acute administration of cytisine or 3-pyr-Cyt did not affect ICSS thresholds. Discontinuation of chronic, 14 days, nicotine administration led to elevations in ICSS thresholds that lasted for about 2 days. Varenicline and cytisine, but not 3-pyr-Cyt, diminished the nicotine withdrawal-induced elevations in ICSS thresholds. In conclusion, these studies indicate that varenicline and cytisine diminish the dysphoric-like state associated with nicotine withdrawal and may thereby prevent relapse to smoking in humans.


Discussion on "Instrumented difference-in-differences" by Ting Ye, Ashkan Ertefaie, James Flory, Sean Hennessy & Dylan S. Small.
We reinterpret the instrumented difference-in-differences (iDID) under a linear instrumental variables (IV) model. Under the linear IV model, we show why iDID is a clear improvement over two existing methods, difference-in-differences (DID) and a cross-sectional, IV analysis. We also re-express some of the assumptions of iDID using familiar, regression-based identification assumptions. We conclude with a method inspired by the linear IV model that can potentially remedy the weak identification problem in iDID.


Violence and aggression in the emergency department: factors impinging on nursing research.
This paper examines issues involved in the debate regarding the role of research in nursing. The authors take the example of violence and aggression in the emergency field to discuss methodological, philosophical, professional, logistical, power differentials and leadership theory that influence and explain the process of conducting research surrounding violence and aggression experienced by nurses working in emergency departments. The paper examines the importance of research and discusses practical issues that impinge or frustrate clinical nursing staff who wish to conduct original research.


Generation of human-melanoma-specific T lymphocyte clones defining novel cytolytic targets with panels of newly established melanoma cell lines.
Melanoma is a cancer where the immune system is believed to play an important role in the control of malignant cell growth. To study the variability of the immune response in melanoma patients, we derived melanoma cell lines from several HLA-A2+ and HLA-A2- patients. The melanoma cell lines studied were designated FM3, FM6, FM9, FM28, FM37, FM45, FM55p, FM55M1 and FM55M2 and were established from eight metastatic tumors as well as from one primary tumor from a total of seven different patients. On the basis of the ability of tumor cells to induce specific cytotoxic T lymphocytes (CTL) from peripheral blood lymphocytes (PBL) in mixed lymphocyte/tumor culture with HLA-A2+ melanoma cells, the FM3 cell line was characterized as highly immunogenic. To investigate the expression of different melanoma-associated antigens recognized by CTL on different melanoma cell lines, we selected the cell line FM3 for restimulation and further T cell cloning experiments. The lytic activity of CTL clones with good proliferative activity was examined using a panel of HLA-A2+ and HLA-A2- melanoma cell lines. None of the tested HLA-A2- melanoma cell lines were susceptible to lysis by the CTL clones, whereas allogeneic HLA-A2+ melanoma cell lines were lysed only by a few CTL clones. On the basis of their reactivity with different melanoma cell lines, it was possible to divide the present CTL clones into at least four groups suggesting the recognition of at least four different antigens. Three of these target structures probably are different from already-described HLA-A2-restricted melanoma-associated antigens, because their expression in the different melanoma cell lines do not correlate with the recognition of melanoma cells by these CTL. The results first indicate that poorly immunogenic melanoma cells may express melanoma-associated antigens, and also suggest that, by using CTL clones obtained against different HLA-class-I-matched melanoma cells, it is possible to define such antigens.


Propofol, a general anesthetic, promotes the formation of fluid phase domains in model membranes.
The molecular site of anesthetic action remains an area of intense research interest. It is not clear whether general anesthetics act through direct binding to proteins or by perturbing the membrane properties of excitable tissues. Several studies indicate that anesthetics affect the properties of either membrane lipids or proteins. However, gaps remain in our understanding of the molecular mechanism of anesthetic action. Recent developments in membrane biology have led to the concept of small-scale domain structures in lipid and lipid--protein coupled systems. The role of such domain structures in anesthetic action has not been studied in detail. In the present study, we investigated the effect of anesthetics on lipid domain structures in model membranes using the fluorescent spectral properties of Laurdan (6-dodecanoyl-2-dimethylamino naphthalene). Propofol, a general anesthetic, promoted the formation of fluid domains in model membranes of dipalmitoyl phosphatidyl choline (DPPC) or mixtures of lipids of varying acyl chains (DPPC:DMPC dimyristoyl phosphatidyl choline 1:1). The estimated size of these domains is 20--50 A. Based on these studies, we speculate that the mechanism of anesthetic action may involve effects on protein--lipid coupled systems through alterations in small-scale lipid domain structures.


Data-driven automated control algorithm for floating-zone crystal growth derived by reinforcement learning.
The complete automation of materials manufacturing with high productivity is a key problem in some materials processing. In floating zone (FZ) crystal growth, which is a manufacturing process for semiconductor wafers such as silicon, an operator adaptively controls the input parameters in accordance with the state of the crystal growth process. Since the operation dynamics of FZ crystal growth are complicated, automation is often difficult, and usually the process is manually controlled. Here we demonstrate automated control of FZ crystal growth by reinforcement learning using the dynamics predicted by Gaussian mixture modeling (GMM) from small numbers of trajectories. Our proposed method of constructing the control model is completely data-driven. Using an emulator program for FZ crystal growth, we show that the control model constructed by our proposed model can more accurately follow the ideal growth trajectory than demonstration trajectories created by human operation. Furthermore, we reveal that policy optimization near the demonstration trajectories realizes accurate control following the ideal trajectory.


Hemispheric asymmetry of feedback-related potentials in a positioning task: comparison of right- and left-handed subjects.
Previous research has demonstrated that delayed nonverbal information feedback (IF) about the correctness of a positioning movement is preceded by a contingent negative variation (CNV) which is larger over the right hemisphere independent of movement side. It was hypothesized that this asymmetry is a manifestation of functional hemispheric specialization, and that, therefore, the distribution of the differences between CNV amplitude measures of the two hemispheres should be different in right-handed and left-handed subjects. The latter group should show a mean asymmetry score closer to zero, and a larger between-subject variance of the asymmetry scores. The present investigation was intended to test these assumptions in samples of rigorously defined right-handers (n = 12) and left-handers (n = 8). The results revealed the expected group differences of the CNV asymmetry scores. In addition, the P1-N1 peak-to-peak amplitude of the IF-evoked potentials was similarly lateralized as the pre-IF CNV and showed the same group differences. In contrast, the handedness groups did not differ in the contralateral lateralization of the movement-related potential shift in the same task.


Congenital self-healing reticulohistiocytosis: report of a patient with a strikingly large tumor mass.
A newborn male Thai infant had numerous brownish red nodules of various sizes scattered over both palms and soles, left thigh, abdomen, chin, and left upper eyelid. An extremely large tumor mass was present on the right sole. Many lesions showed spontaneous ulceration. No extracutaneous involvement was found. All lesions involuted spontaneously within two to three months, some with scar formation. Histology showed large numbers of mononucleated and multinucleated histiocytic cell infiltrations, 10% of which contained Birbeck's granules. Areas of necrosis and calcification were also seen in the largest tumor. No recurrence was observed after follow-up for three years.


Role of hepatitis B virus genotypes in chronic hepatitis B exacerbation.
Hepatitis B virus (HBV) genotypes and precore and core promoter mutations were determined in 318 patients with HBV. Patients infected with HBV genotype B had a higher median alanine aminotransferase level and bilirubin level and a lower median albumin level during exacerbations of disease, compared with patients infected with HBV genotype C (all P<.001). By logistic regression analysis, HBV genotype B infection (P=.014) and low albumin levels (P=.006) were independently associated with a higher risk of hepatic decompensation during severe exacerbations of disease. Patients infected with genotype B had a significantly higher mortality due to hepatic decompensation than did patients with genotype C (70% vs. 27.8%; P=.05).


Formation of microsomal cytochrome P-450 complexes studied by the NMR relaxation of water.
Cytochrome P-450 in microsomes from liver of phenobarbital treated and control rats has been studied by light absorption and by magnetic resonance methods (EPR and NMR). The nuclear relaxation rate of water protons was measured for microsomal suspensions in the presence of various reactants of Type I and II. The change of relaxation rates correlates well with the spin state conversion of the heme iron. No competition between eventual inner-sphere water molecules and the reactants seems to occur. The temperature dependence of the low spin to high spin equilibrium was studied by light absorption and was accounted for in the temperature variation of the molar relaxation rates of the two spin states.


Measuring COVID-19 related anxiety and obsession: Validation of the Coronavirus Anxiety Scale and the Obsession with COVID-19 Scale in a probability Chinese sample.
With concern over the rise in mental health symptoms associated with the COVID-19 pandemic, the present study set out to address the absence of pandemic-specific screening tools for detecting those in Chinese societies who are at-risk for experiencing mental distress due to the pandemic; thus, its aim was to validate the Coronavirus Anxiety Scale (CAS) and Obsession with COVID-19 Scale (OCS) in Chinese adults. With a two-stage cluster random sampling method, we surveyed 1011 Chinese community-dwelling adults (38.8% men; 41.2 years old on average with an SD of 15.8) in June and July of 2020. Our psychometric evaluation results showed that the Chinese version of CAS and OCS retained their original one-dimensional structure and demonstrated measurement invariance across genders. In line with validation studies of the CAS and OCS in other languages, subsequent analyses also provided support to our Chinese version with respect to their satisfactory internal consistency (α = .87 and .73, respectively), and good concurrent validity (i.e., positive associations with negative feelings, excessive time-consumption, subjective distress, and functioning impairment). Due to constraints of time and cross-sectional design, we only validated CAS and OCS among Chinese adults and did not evaluate their test-retest reliability nor predictive validity. Considering the practical benefits of understanding the source of mental symptoms during the pandemic, we recommend the use of CAS and OCS in Chinese communities to facilitate early identification and intervention for those who require clinical attention due to their COVID-19 related anxiety and obsessive thoughts.


Comparison of intensity-modulated radiation therapy alone vs. intensity-modulated radiation therapy combined with chemotherapy in elderly nasopharyngeal carcinoma patients (aged >65 years).
The efficacy and tolerability of adding chemotherapy to radiotherapy in the era of intensity-modulated radiation therapy (IMRT) remain controversial among older patients with nasopharyngeal carcinoma (NPC). The present study compared IMRT alone with IMRT in combination with chemotherapy in elderly NPC patients. Between January 2011 and December 2014, 102 patients aged >65 years with NPC who received IMRT alone (IMRT group) or IMRT in combination with chemotherapy (IMRT/CT group) were enrolled. Patients from both treatment arms were pair-matched (1:1 ratio) based on six clinical factors. Differences in overall survival (OS), disease-free survival (DFS), locoregional relapse-free survival (LRRFS), and distant metastasis-free survival (DMFS) were assessed using the Kaplan-Meier method and Cox proportional hazards models, whereas the toxicity profile was assessed using Common Terminology Criteria for Adverse Events (CTCAE) version 4. No significant differences were noted in OS (72.1% vs. 72.5%, p = 0.799), DFS (65.9% vs. 70.1%, p = 0.733), LRRFS (76.4% vs. 71.6%, p = 0.184), and DMFS (90.8% vs. 98.0%, p = 0.610) between the IMRT and IMRT/CT groups. Multivariate analyses showed that chemotherapy was not an independent factor for OS, DFS, LRRFS, and DMFS. However, the incidences of grade 3 vomiting/nausea (p = 0.000), leukopenia/neutropenia (p = 0.000), thrombocytopenia (p = 0.041), and anemia (p = 0.040) were significantly higher in the IMRT/CT group compared with the IMRT group. No grade 4 toxicities were observed. IMRT alone was similar to IMRT/CT in treating elderly NPC patients (age >65 years), with comparable survival outcomes and less grade 3 toxicities.


Vulnerability to air pollution health effects.
Ambient air pollution can have adverse effects on the health of exposed populations, but individuals or groups are not equally vulnerable, and pollution reduction benefits are likely to be unevenly distributed within a population. While the use of total-population risks is a valid approach for public health protection, it is increasingly recognized that more attention on vulnerable groups is necessary. This paper describes population vulnerability to the health effects of air pollutants using risk analysis concepts and based on available evidence. Publications reporting air pollution health risks for specific sub-populations, or more conceptual discussions of vulnerability, were selected following a literature search of the PubMed database. Only studies in the context of developed countries were included. Information on population characteristics and factors that can influence risk was assessed from the perspective of the vulnerability framework, and was used to outline interactions with biological susceptibility, exposure, and social coping. Population characteristics encompass several factors that interact and confer vulnerability. Age, for example, regarded as significant mostly in terms of physiology, also relates to exposure through behaviours and activities that can be more amenable to prevention. Children are recognized as a high-risk group but their vulnerability may differ by childhood stage, while pregnant women are not explicitly identified as a vulnerable group despite growing evidence for reproductive risks. Social-economic factors have received little attention, although they can affect coping capacity as well as interact with susceptibility and exposure to air pollution. Evidence for vulnerability components often lies in different fields of study and has not been evaluated in an integrated manner. Better understanding of population vulnerability can improve the scientific basis to assess risks and develop policies or other health protection initiatives to reduce the impacts of air pollution.


Hyperactivity in anorexia nervosa: a case study using experience sampling methodology.
Hyperactivity is frequently observed in eating disorders, and several biopsychological mechanisms have been proposed to explain its pathogenetic role. In view of the lack of a reliable method to study hyperactive behavior, we did an experiment with experience sampling methodology (ESM). During 1 week, an anorexia nervosa (AN) patient was asked at nine random times a day to report her momentary tendency to be physically active, her emotions and several other variables including calorie expenditure, drive for thinness, attractiveness, obsessions, compulsions, and attitudes towards hyperactivity. Results indicate that the patient's tendency to be hyperactive was (a) positively related to her weight preoccupation and her negative emotions, and (b) negatively related to her positive emotions and the absence of depression. In this patient, obsessions and compulsions were not related to hyperactivity. The usefulness of ESM for studying the role of hyperactivity in AN is discussed.


Role of endogenous enkephalins in locomotion and nociception studied with peptidase inhibitors in two inbred strains of mice (C57BL/6J and DBA/2J).
Acetorphan, a parenterally active enkephalinase inhibitor, induced dose-dependently a naloxone-reversible analgesia on the hot-plate jump test in DBA/2J (DBA2) mice but was devoid of effects in C57BL/6J (C57) mice. By contrast, acetorphan increased locomotion in both strains; however, the DBA2 strain was much more sensitive than C57 mice to the locomotor stimulant effect. The increased locomotion was antagonized by naloxone in both strains. These data suggest that endogenous enkephalins modulate nociception and locomotion in the two inbred strains differently.


Acute Myeloid Leukemia Stem Cells in Minimal/Measurable Residual Disease Detection.
Acute myeloid leukemia (AML) is a hematological malignancy characterized by an abundance of incompletely matured or immature clonally derived hematopoietic precursors called leukemic blasts. Rare leukemia stem cells (LSCs) that can self-renew as well as give rise to leukemic progenitors comprising the bulk of leukemic blasts are considered the cellular reservoir of disease initiation and maintenance. LSCs are widely thought to be relatively resistant as well as adaptive to chemotherapy and can cause disease relapse. Therefore, it is imperative to understand the molecular bases of LSC forms and functions during different stages of disease progression, so we can more accurately identify these cells and design therapies to target them. Irrespective of the morphological, cytogenetic, and cellular heterogeneity of AML, the uniform, singularly important and independently significant prognosticator of disease response to therapy and patient outcome is measurable or minimal residual disease (MRD) detection, defined by residual disease detection below the morphology-based 5% blast threshold. The importance of LSC identification and frequency estimation during MRD detection, in order to make MRD more effective in predicting disease relapse and modifying therapeutic regimen is becoming increasingly apparent. This review focuses on summarizing functional and cellular composition-based LSC identification and linking those studies to current techniques of MRD detection to suggest LSC-inclusive MRD detection as well as outline outstanding questions that need to be addressed to improve the future of AML clinical management and treatment outcomes.


Pharmacogenetic analyses of cisplatin-induced nephrotoxicity indicate a renoprotective effect of ERCC1 polymorphisms.
We investigated whether genetic polymorphisms may contribute to the interpatient variability of cisplatin-induced nephrotoxicity. Polymorphisms in the candidate genes GSTM1, GSTT1, OCT1, OCT2, LARP2, ERCC1, XRCC1 and EPO were analyzed for associations with nephrotoxicity in 79 cancer patients receiving cisplatin-containing chemotherapy. Higher cisplatin dose was associated with strongly decreased estimated glomerular filtration rates (eGFR) (r(2) = 0.205). Two highly genetically linked polymorphisms in the ERCC1 gene, 8092C>A and Asn118Asn, were significantly associated with change in eGFR, accounting for an additional 13% of interindividual variability. Homozygous carriers of the 8092A allele in ERCC1 showed no reduction in eGFR, compared with the 11.5% mean eGFR decrease in C allele carriers (p = 0.004). Homozygous carriers of the C allele of Asn118Asn showed no reduction in eGFR, compared with the 12.8% mean eGFR decrease seen in T allele carriers (p = 0.047). Polymorphisms in the other candidate genes were not associated with cisplatin-induced nephrotoxicity. Genetic polymorphisms in ERCC1 may be valuable predictors of cisplatin-induced nephrotoxicity.


Calcium carbonate in cholesterol gallstones.
CaCO3 has been studied in twelve gallstones in which cholesterol predominated. Different polymorphs of CaCO3, as well as carbonate-apatite, were characterised by X-ray diffraction, polarised light microscopy and scanning electron microscopy. Crystals and rhombohedral aggregates of calcite, aggregates of small crystals and tabular crystals of vaterite and fibrous radial aggregates in the form of ooliths were found. In microscopic studies on sections of the stones, CaCO3 was localised mainly in the periphery in the form of layers or bands associated with calcium bilirubinate which was deposited in close relation to it. The phenomena contributing to the precipitation of CaCO3 are discussed, as is the importance of the latter in resistance to the pharmacologic treatment of gallstone disease.


How is the usability of commercial activity monitors perceived by older adults and by researchers? A cross-sectional evaluation of community-living individuals.
Using commercial activity monitors may advance research with older adults. However, usability for the older population is not sufficiently established. This study aims at evaluating the usability of three wrist-worn monitors for older adults. In addition, we report on usability (including data management) for research. Data were collected cross-sectionally. Between-person of three activity monitor type (Apple Watch 3, Fitbit Charge 4, Polar A370) were made. The activity monitors were worn in normal daily life in an urban community in Germany. The period of wear was 2 weeks. Using convenience sampling, we recruited N=27 healthy older adults (≥60 years old) who were not already habitual users of activity monitors. To evaluate usability from the participant perspective, we used the System Usability Scale (SUS) as well as a study-specific qualitative checklist. Assessment further comprised age, highest academic degree, computer proficiency and affinity for technology interaction. Usability from the researchers' perspective was assessed using quantitative data management markers and a study-specific qualitative check-list. There was no significant difference between monitors in the SUS. Female gender was associated with higher SUS usability ratings. Qualitative participant-usability reports revealed distinctive shortcomings, for example, in terms of battery life and display readability. Usability for researchers came with problems in data management, such as completeness of the data download. The usability of the monitors compared in this work differed qualitatively. Yet, the overall usability ratings by participants were comparable. Conversely, from the researchers' perspective, there were crucial differences in data management and usability that should be considered when making monitor choices for future studies.


Achieving zero extinction for land plants.
Despite the importance of plants for humans and the threats to their future, plant conservation receives far less support compared with vertebrate conservation. Plants are much cheaper and easier to conserve than are animals, but, although there are no technical reasons why any plant species should become extinct, inadequate funding and the shortage of skilled people has created barriers to their conservation. These barriers include the incomplete inventory, the low proportion of species with conservation status assessments, partial online data accessibility, varied data quality, and insufficient investment in both in and ex situ conservation. Machine learning, citizen science (CS), and new technologies could mitigate these problems, but we need to set national and global targets of zero plant extinction to attract greater support.


Applications of Digital and Computational Pathology and Artificial Intelligence in Genitourinary Pathology Diagnostics.
As machine learning (ML) solutions for genitourinary pathology image analysis are fostered by a progressively digitized laboratory landscape, these integrable modalities usher in a revolution in histopathological diagnosis. As technology advances, limitations stymying clinical artificial intelligence (AI) will not be extinguished without thorough validation and interrogation of ML tools by pathologists and regulatory bodies alike. ML solutions deployed in clinical settings for applications in prostate pathology yield promising results. Recent breakthroughs in clinical artificial intelligence for genitourinary pathology demonstrate unprecedented generalizability, heralding prospects for a future in which AI-driven assistive solutions may be seen as laboratory faculty, rather than novelty.


Some aspects of the ecology of the desert snail Sphincterochila prophetarum in relation to energy and water flow.
Between 1976-1978, we studied the ecology of the Sphincterochila prophetarum, the most common snail, on stony slopes in Northern Negev. Energy and water flow determinations were made at the individual and population levels on a field observation basis and metabolic data were derived from laboratory simulations.The snails are active during 5-7% of the time during the year, while the remaining 95% of the time, the snails are in aestivation under stones. The energy and water inputs during the short feeding periods are very fast. Only 8% of the total energy in the eaten food are assimilated. Eighty-nine percent of the total assimilated energy are utilized in respiration during the various periods of activity and dormancy.The water loss during the feeding and activity period is about 37% of the total annual input. The snails lose twice as much the amount of water during the winter dormancy periods than in the summer dormancy period.


Sadness, depression and social reciprocity in highland Ecuador.
Pena or llaqui in the Quechua area of Ecuador refers to a state of sadness and depression experienced following a variety of life events. This paper tries to explain why there is an elaborate discourse on such feelings in this culture. It is argued that the Quechuas stress the ideal of social reciprocity in human encounters and are accordingly sensitive to disturbances in social relationships. We observe that they pay a great deal of attention to the victim of pena and that they try to improve relationships with the social network and the family. The indigenous theory on pena also points to the importance of bodily elements closely associated to the psychological conditions. We conclude that knowledge of status relationships are important to understand the emotions experienced when loss occurs.


Facial Beautification and Rejuvenation with Injectables: My Preferred Approach.
Asians are of different ethnic origins. Nevertheless, they share the common facial structural deficiencies and consequences of the aging process that create the opportunity for esthetic intervention. As a result, Injectables are widely used in young Asians to achieve an oval facial shape with increased facial height and projection. In mature Asians with lifelong structural deficiencies, the beauty treatment plan is more complex than removal of signs of aging. Therefore, apart from injectables, other treatment modalities for tissue repositioning, neocollagenesis and skin quality improvement are also required to obtain the optimal result.


Passive protection of NMRI mice against Serratia marcescens: comparative efficacy of commercial human IgG immunoglobulin preparations and rabbit anti-O, -H, -K, -life cell and -protease immune sera.
Three commercial, intravenously applicable human IgG preparations passively protected NMRI mice against intraperitoneal challenge with 11 of 19 selected, serologically defined O-antigen reference strains and clinical, nosocomially significant isolates of Serratia marcescens. Conventional anti-O and anti-H, but not anti-K and anti-protease, rabbit immune sera revealed passive protective capacity against homologous challenge strains; however, anti-O rabbit immune sera failed to invariably protect against heterologous test strains that carried identical serogroup O-antigens. The passive protective efficacy of anti-live cell immune sera, derived from rabbits following recovery from experimental septicemia, was abolished through dual absorption with homologous O-cells. It was concluded that antibodies directed against O-antigens, i.e., lipopolysaccharide moieties, of the challenge strains of S. marcescens afforded passive protection.


Analysis of bone transport for ankle arthrodesis as a limb salvage procedure for the treatment of septic pilon fracture nonunion.
Septic nonunion of the pilon region with ankle joint infection is challenging for orthopedic surgeons to treat and is associated with a high risk of limb loss. Therefore, the aim of this study was to evaluate the effectiveness of bone transport for ankle arthrodesis in salvaging the limp after septic ankle destruction of the pilon region. We conducted a single-center, retrospective study including 21 patients treated for septic pilon nonunion with accompanying septic ankle destruction via Ilizarov bone transport between 2004 and 2018. In all cases, the complete excision of the nonunion and the resection of the ankle joint were carried out, followed by treating the bone and joint defect with a bone transport into the ankle arthrodesis. In 12/21 patients an additional flap transfer was required due to an accompanying soft tissue lesion. The overall healing and failure rate, final alignment and complications were recorded by the patients' medical files. The bone-related and functional results were evaluated according to the Association for the Study and Application of Methods of Ilizarov (ASAMI) scoring system and a modified American Orthopedic Foot and Ankle Society (AOFAS) scale. After a mean follow-up of 30.9 ± 15.7 months (range 12-63 months), complete bone and soft tissue healing occurred in 18/21 patients (85.7%). The patients had excellent (5), good (7), fair (4), and poor (3) results based on the ASAMI functional score. Regarding bone stock, 6 patients had excellent, 7 good, and 6 fair results. The modified AOFAS score reached 60.6 ± 18 points (range, 29-86). In total, 33 minor complications and 28 major complications occurred during the study period. In 2 cases, a proximal lower leg amputation was performed due to a persistent infection and free flap necrosis with a large soft tissue defect, whereas in one case, persistent nonunion on the docking side was treated with a carbon orthosis because the patient refused to undergo an additional surgery. Bone transport for ankle arthrodesis offers the possibility of limb salvage after septic ankle destruction of the pilon region, with acceptable bony and functional results. However, a high number of complications and surgical revisions are associated with the treatment of this severe complication after pilon fracture.


Percutaneous sonographically guided interstitial US ablation: experimentation in an in vivo pig liver model.
To test the feasibility and efficacy of a percutaneous sonographically guided high-intensity interstitial ultrasound (US) ablation applicator to create "macrolesions" of confluent coagulation in an in vivo pig liver model. Eight pigs and an interstitial US ablation applicator were used for this study. Elementary lesions and macrolesions created by the confluence of several elementary lesions were successively analyzed. The first phase of the study was performed by varying the acoustic intensity (AI) to create elementary lesions. The second phase of the study aimed at creating macrolesions in three target zones previously defined in the liver. Mean (+/- SD) maximum and minimum diameters of the macrolesions were calculated. The elementary lesions created with AIs of 30, 40, and 55 W/cm(2) measured 14.9 mm +/- 3, 19.8 mm +/- 5, and 13.2 mm +/- 3, respectively. The AI retained for the second experimental phase was 40 W/cm(2). Because of the flamelike aspect of the elementary lesions, the macrolesion appeared as a cylinder with crenelated contours. On macroscopic examination, mean maximum diameters of the macrolesions were 28.7 mm +/- 3, 34.1 mm +/- 2, and 27.8 mm +/- 5 and mean minimum diameters of the macrolesions were 14 mm +/- 3, 18.7 mm +/- 2, and 14 mm +/- 3 for the three target zones, respectively. A single major complication, puncture of the gallbladder, occurred in one animal. A percutaneous sonographically guided interstitial ablation applicator is able to create macrolesions of coagulation in pig liver.


How Pseudoscience Generated US Material and Device Regulations.
The images in the American Medical Association's Historic Health Fraud and Alternative Medicine Collection include quack devices from the early 20th century, which gave rise to regulatory and professional oversight.


Binding of human ACE2 and RBD of Omicron enhanced by unique interaction patterns among SARS-CoV-2 variants of concern.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus causing COVID-19, has continued to mutate and spread worldwide despite global vaccination efforts. In particular, the Omicron variant, first identified in South Africa in late November 2021, has become the dominant strain worldwide. Compared to the original strain identified in Wuhan, Omicron features 50 genetic mutations, with 15 mutations in the receptor-binding domain (RBD) of the spike protein, which binds to the human angiotensin-converting enzyme 2 (ACE2) receptor for viral entry. However, it is not completely understood how these mutations alter the interaction and binding strength between the Omicron RBD and ACE2. In this study, we used a combined steered molecular dynamics (SMD) simulation and experimental microscale thermophoresis (MST) approach to quantify the interaction between Omicron RBD and ACE2. We report that the Omicron brings an enhanced RBD-ACE2 interface through N501Y, Q498R, and T478K mutations; the changes further lead to unique interaction patterns, reminiscing the features of previously dominated variants, Alpha (N501Y) and Delta (L452R and T478K). Among the Q493K and Q493R, we report that Q493R shows stronger binding to ACE2 than Q493K due to increased interactions. Our MST data confirmed that the Omicron mutations in RBD are associated with a five-fold higher binding affinity to ACE2 compared to the RBD of the original strain. In conclusion, our results could help explain the Omicron variant's prevalence in human populations, as higher interaction forces or affinity for ACE2 likely promote greater viral binding and internalization, leading to increased infectivity.


Virus-like particle vaccine with B-cell epitope from porcine epidemic diarrhea virus (PEDV) incorporated into hepatitis B virus core capsid provides clinical alleviation against PEDV in neonatal piglets through lactogenic immunity.
Porcine epidemic diarrhea virus (PEDV) has had a negative economic impact on the global swine industry for decades since its first emergence in the 1970s in Europe. In 2013, PEDV emerged for the first time in the United States, causing immense economic losses to the swine industry. Efforts to protect U.S. swine herds from PEDV infection and limit PEDV transmission through vaccination had only limited success so far. Following the previous success in our virus-like particle (VLP) based vaccine in mouse model, in this study we determined the immunogenicity and protective efficacy of a VLP-based vaccine containing B-cell epitope 748YSNIGVCK755 from the spike protein of PEDV incorporated into the hepatitis B virus core capsid (HBcAg), in a comprehensive pregnant gilt vaccination and piglet challenge model. The results showed that the vaccine was able to induce significantly higher virus neutralization response in gilt milk, and provide alleviation of clinical signs for piglets experimentally infected with PEDV. Piglets from pregnant gilt that was vaccinated with the VLP vaccine had faster recovery from the clinical disease, less small intestinal lesions, and higher survival rate at 10 days post-challenge (DPC).


Functionally restricted, allospecific, human helper T cell lines that amplify either B cell or cytolytic T cell responses.
Using a panel of partially cloned, OKT4+, DRw-1-specific, alloproliferative human T cell lines, we have identified two functionally restricted and reciprocating types of helper T cells. One provides major histocompatibility complex-restricted help for plaque-forming cell responses by DRw 1+ allogeneic B cells; the other preferentially amplifies the generation of allospecific cytotoxic T lymphocytes (CTL) from CTL precursors that have been suboptimally triggered by alloantigen.


A controlled release system of titanocene dichloride by electrospun fiber and its antitumor activity in vitro.
In order to improve both safety and efficacy of cancer chemotherapy of titanocene dichloride and overcome the shortcomings such as instability and short half-life in the human body, we report a controlled release system of titanocene dichloride by electrospun fiber and its in vitro antitumor activity against human lung tumor spca-1 cells. The system was developed by electrospinning. The release profiles of titanocene dichloride in PBS were researched by UV-Vis spectrophotometer. In vitro antitumor activities of the fibers were examined by MTT method. Titanocene dichloride was well incorporated in biodegradable poly(L-lactic acid) fibers. XRD results suggest that titanocene dichloride exists in the amorphous form in the fibers. The controlled release of titanocene dichloride can be gained for long time. MTT showed actual titanocene dichloride content 40, 80, 160 and 240 mg/L from the fibers mat, cell growth inhibition rates of 11.2%, 22.1%, 44.2% and 68.2% were achieved, respectively. The titanocene dichloride released has obvious inhibition effect against lung tumor cells. The system has an effect of controlled release of titanocene dichloride and may be used as an implantable anticancer drug in clinical applications in the future.


Differential effects of estrogen on hippocampal- and striatal-dependent learning.
Estrogen's role in learning and memory may be to predispose animals to use specific cognitive strategies (Korol & Kolo, 2002). Specifically, estrogen may facilitate hippocampal-dependent learning, while at the same time attenuate striatal-dependent learning. As a stringent test of this hypothesis, place or response learning on an eight-arm radial maze was compared between ovariectomized (OVX) female Long-Evans rats and rats with chronic estrogen replacement (OVX+E; 5mg 17-beta estradiol 60-day release tablet). Reference and working memory errors were monitored separately for both place and response learning tasks. OVX+E rats learned the place task significantly faster than the response task, and faster than OVX rats. OVX rats required fewer days to reach criterion on the response task than OVX+E rats. Estrogen selectively enhanced reference memory performance, but only during place learning. The specific pattern of estrogen effects on learning suggests that future studies include verification of cognitive strategies used by animals.


Recombination between Streptococcus suis ICESsu32457 and Streptococcus agalactiae ICESa2603 yields a hybrid ICE transferable to Streptococcus pyogenes.
Integrative conjugative elements (ICEs) are mobile genetic elements that reside in the chromosome but retain the ability to undergo excision and to transfer by conjugation. Genes involved in drug resistance, virulence, or niche adaptation are often found among backbone genes as cargo DNA. We recently characterized in Streptococcus suis an ICE (ICESsu32457) carrying resistance genes [tet(O/W/32/O), tet(40), erm(B), aphA, and aadE] in the 15K unstable genetic element, which is flanked by two ∼1.3kb direct repeats. Remarkably, ∼1.3-kb sequences are conserved in ICESa2603 of Streptococcus agalactiae 2603V/R, which carry heavy metal resistance genes cadC/cadA and mer. In matings between S. suis 32457 (donor) and S. agalactiae 2603V/R (recipient), transconjugants were obtained. PCR experiments, PFGE, and sequence analysis of transconjugants demonstrated a tandem array between ICESsu32457 and ICESa2603. Matings between tandem array-containing S. agalactiae 2603V/R (donor) and Streptococcus pyogenes RF12 (recipient) yielded a single transconjugant containing a hybrid ICE, here named ICESa2603/ICESsu32457. The hybrid formed by recombination of the left ∼1.3-kb sequence of ICESsu32457 and the ∼1.3-kb sequence of ICESa2603. Interestingly, the hybrid ICE was transferable between S. pyogenes strains, thus demonstrating that it behaves as a conventional ICE. These findings suggest that both tandem arrays and hybrid ICEs may contribute to the evolution of antibiotic resistance in streptococci, creating novel mobile elements capable of disseminating new combinations of antibiotic resistance genes.


Two-dimensional and Doppler echocardiographic assessment of neonatal arterial repair for transposition of the great arteries.
The arterial switch procedure has become an accepted reparative technique for transposition of the great arteries with or without ventricular septal defect. In this study the accuracy of prospective noninvasive imaging in detecting arterial tract obstruction and the prevalence and severity of arterial valvular regurgitation (as assessed by Doppler ultrasound) were evaluated in survivors of arterial repair. All 53 study patients underwent two-dimensional echocardiographic examination 2 days to 20 months (median 7 months) postoperatively; 43 patients also had pulsed and continuous wave Doppler studies. The accuracy of the noninvasive evaluation of arterial tract obstruction was determined by comparison of Doppler maximal instantaneous gradients with peak to peak gradients at nonsimultaneous catheterization in 26 patients. Twenty-one (81%) of the 26 patients underwent catheterization and successful pulsed and continuous wave Doppler examination of the right heart; 17 (81%) of these 21 had a maximal pressure gradient within 20 mm Hg of the peak to peak gradient obtained at catheterization. Echocardiographic identification of the stenotic site was correct in all eight of the patients in this group requiring reoperation. Twenty-three (88%) of the 26 patients who underwent catheterization had successful Doppler interrogation of the aortic tract; 22 (96%) of these 23 had a maximal instantaneous gradient within 20 mm Hg of the peak to peak catheterization gradient. Fourteen (32%) of 43 patients had mild or moderate pulmonary regurgitation by Doppler study. Three (7%) of the 43 had mild aortic regurgitation.


Treatment of recurrent retinal detachment secondary to optic nerve coloboma with injection of autologous platelet concentrate.
A 14-year-old girl presented with a recurrent retinal detachment secondary to optic nerve coloboma in her left eye with a small retinal hole in the bed of the coloboma, confirmed by optical coherence tomography. The patient was treated by injection of 0.05 mL of autologous platelet concentrate into the coloboma along with vitrectomy and gas exchange. After 8 months, the retina was attached and optical coherence tomography revealed closure of the retinal hole. Considering our experience, autologous platelet injection may be considered a treatment option for recurrent retinal detachment secondary to optic nerve coloboma.


Balloon valvuloplasty for treating pulmonic, mitral and aortic valve stenosis.
Percutaneous balloon valvuloplasty is a technique that has been developed in the cardiac catheterization laboratory over the last 5 years for the treatment of pulmonic, mitral and aortic valve stenosis in children and adults. This review will attempt to summarize recent advances in this new field of invasive cardiology over the last several years.


Using Milk Thistle (Silybum marianum) Extract to Improve the Welfare, Growth Performance and Meat Quality of Broiler Chicken.
Modern poultry production looks for feed and water additives that improve the welfare of chickens. The utilization of herbs as additives in feed or drinking water is becoming increasingly well known. The aim of this study was to determine the effect of milk thistle extract (Silybum marianum), administered in drinking water, on chickens' welfare, production results, selected physicochemical properties of the breast muscles, the activity of selected enzymes, and the antioxidant potential of blood serum and breast muscles. A total of 102 one-day-old male ROSS 308 chicks were allocated into three treatment groups. The material was an infusion of dried milk thistle seeds in two doses, administered in drinking water for chickens (group: C = 0; E1 = 0.24; E2 = 0.36 g/day/animal) under standard rearing conditions. As a result of adding the milk thistle to the drinking water, there was an improvement in the welfare of the chickens and in the production results, enzymatic capacity of selected enzymes, and antioxidant capacity in the blood serum and in pectoral muscle (p ≤ 0.05). The addition of a milk thistle seed infusion for chickens can be used in poultry production to improve the rearing performance antioxidant capacity and welfare of chickens.


A genetic study of affective disorders.
First and second degree relatives of 99 probands with affective disorders (49 unipolar and 50 bipolar subjects) were studied. The high risk values obtained for affective disorders were shown to be compatible with those found by other authors, although the prevalence of the illness in the population of Lombardy appears to be much lower than in other countries. Very low rates of suicide and alcoholism were found in our sample. Data obtained by analysis of the affected pairs of relatives rule out the hypothesis of a dominant X-linked gene if the bipolar and the unipolar forms are considered genetically separated entities. Results compatible with a polygenic condition, partially shared by bipolar patients, were found using Slater's and Smith & Falconer's methods. Our data, however, cannot rule out the dominant hypothesis.