The clinical and histomorphological features of pityriasis rubra pilaris. A comparative analysis with psoriasis.
Pityriasis rubra pilaris (PRP) is an idiopathic erythematous scaling eruption which can be difficult to distinguish from psoriasis. We explored the clinical features, including background medical illnesses and potential triggers in patients with PRP, and also its histomorphologic spectrum. Patients with PRP were selected by natural language search of dermatopathology databases containing 250,000 cases accessioned over a 3-year period. A detailed medical history was obtained on each patient via office chart review and patient interviews. We compared the histologic findings in skin biopsies from patients with PRP to those of biopsies matched for site and age from control patients with psoriasis. Certain aspects of the clinical presentations encountered in the study group patients have not been previously emphasized, including eruptions compatible with a vesiculobullous disorder in 4 patients. Several patients had evidence of underlying iatrogenic or systemic immune dysregulatory states and certain triggers could be isolated such as emotional stress and prior exposure to microbial pathogens. Histomorphologic features predictive of PRP included follicular plugging, an increased granular cell layer, and acantholysis. While seen in a minority of biopsies of PRP, morphologic discriminators supportive of a diagnosis of psoriasis included neutrophils in the parakeratotic scale crust, and dermal papillae capillary ectasia with vessels lying in direct apposition to the epidermis. Other morphologic features were encountered in biopsies of PRP which have received little emphasis in the dermatopathology literature, including epithelial atrophy, significant dermal inflammation, the presence of eosinophils and plasma cells within the inflammatory infiltrates, an abnormal granular cell layer, and epidermolytic hyperkeratosis, albeit none were statistically signficant predictors of PRP over psoriasis. Nevertheless, their identification emphasizes the varied histologic spectrum of PRP. The almost ubiquitous finding of acantholysis and the presence of an abnormal granular cell layer in many biopsies of PRP suggests that abnormal keratins or defects in the retinol signalling pathway may be of pathogenetic importance.


Tannic acid as an electron microscope tracer for permeable cell membranes.
To recognize damaged cells in preparations for transmission electron microscopy, high molecular weight (1700 MW) tannic acid (1-4%) has been added to glutaraldehyde fixing solutions. During fixation, the tannic acid penetrates only those cells whose plasma membranes were previously damaged. It enhances the electron density of the injured cells, which become clearly distinguishable from the undamaged ones. As a tracer tannic acid shows great advantages over either lanthanum hydroxide, ruthenium red, or horseradish peroxidase. It diffuses evenly throughout the tissue block and is not removed by preparative steps. Furthermore, it is also a good tracer at the light microscope level.


Biologic versus synthetic prosthesis for chest wall reconstruction: a matched analysis.
The aim of this study was to compare postoperative outcomes between biologic and synthetic reconstructions after chest wall resection in a matched cohort. All patients who underwent reconstruction after full-thickness chest wall resection from 2000 to 2022 were reviewed and stratified by prosthesis type (biologic or synthetic). Biologic prostheses were of biologic origin or were fully absorbable and incorporable. Integer matching was performed to reduce confounding. The study end point was surgical site complications requiring reoperation. Multivariable analysis was performed to identify associated risk factors. In total, 438 patients underwent prosthetic chest wall reconstruction (unmatched: biologic, n = 49; synthetic, n = 389; matched: biologic, n = 46; synthetic, n = 46). After matching, the median (interquartile range) defect size was 83 cm2 (50-142) for the biologic group and 90 cm2 (48-146) for the synthetic group (P = 0.97). Myocutaneous flaps were used in 33% of biologic reconstructions (n = 15) and 33% of synthetic reconstructions (n = 15) in the matched cohort (P = 0.99). The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic reconstructions in the unmatched (3 [6%] vs 29 [7%]; P = 0.99) and matched (2 [4%] vs 4 [9%]; P = 0.68) cohorts. On the multivariable analysis, operative time [adjusted odds ratio (aOR) = 1.01, 95% confidence interval (CI), 1.00-1.01; P = 0.006] and operative blood loss (aOR = 1.00, 95% CI, 1.00-1.00]; P = 0.012) were associated with higher rates of surgical site complications requiring reoperation; microvascular free flaps (aOR = 0.03, 95% CI, 0.00-0.42; P = 0.024) were associated with lower rates. The incidence of surgical site complications requiring reoperation was not significantly different between biologic and synthetic prostheses in chest wall reconstructions.


The high-risk pediatric patient for ambulatory surgery.
The aim of this article is to briefly review the pediatric ambulatory surgery landscape, identify two of the most common comorbidities affecting this population, examine the influence of pediatric obesity and sleep disordered breathing (SDB)/obstructive sleep apnea (OSA) on perioperative care, and provide information that can be used when formulating site specific criteria for ambulatory surgical centers. Most pediatric surgeries performed are now ambulatory, a majority of which take place outside of academic centers. Children with comorbidities such as obesity and SDB/OSA are undergoing surgical or diagnostic procedures which were previously deemed unacceptable for ambulatory surgery. The increase in pediatric ambulatory surgery coupled with a recent shortage of pediatric anesthesiologists means many children will receive anesthesia care from general clinicians who care for children intermittently and may be unfamiliar with the perioperative risks these comorbidities can present. Our pediatric ambulatory surgical population is anticipated to demonstrate increasing rates of obesity and SDB/OSA. Bringing attention to potential perioperative complications associated with these comorbidities provides a stronger foundation upon which to formulate criteria for individual ambulatory centers. It allows for targeted anesthetic management, influences provider assignments and/or staffing ratios, and informs scheduling times. For anesthesiologists who do not practice pediatric anesthesia daily, knowing what to anticipate plays a significant role in the ability to eliminate surprises and care for these patients safely.


Benchmarking electronic medical records initiatives in the US: a conceptual model.
This article provides a conceptual model for benchmarking the use of clinical information systems within healthcare organizations. Additionally, it addresses the benefits of clinical information systems which include the reduction of errors, improvement in clinical decision-making and real time access to patient information. The literature suggests that clinical information systems provide financial benefits due to cost-savings from improved efficiency and reduction of errors. As a result, healthcare organizations should adopt such clinical information systems to improve quality of care and stay competitive in the marketplace. Our research clearly documents the increased adoption of electronic medical records in U.S. hospitals from 2005 to 2007. This is important because the electronic medical record provides an opportunity for integration of patient information and improvements in efficiency and quality of care across a wide range of patient populations. This was supported by recent federal initiatives such as the establishment of the Office of the National Coordinator of Health Information Technology (ONCHIT) to create an interoperable health information infrastructure. Potential barriers to the implementation of health information technology include cost, a lack of financial incentives for providers, and a need for interoperable systems. As a result, future government involvement and leadership may serve to accelerate widespread adoption of interoperable clinical information systems.


Evaluation of racing performance after colic surgery in Thoroughbreds: 85 cases (1996-2010).
To determine racing performance after surgery for colic in Thoroughbreds. Retrospective cohort study. 85 racing Thoroughbreds that survived to discharge following colic surgery and 170 race-matched reference horses. Earnings, starts, and earnings per start were compared between horses that underwent surgery and reference horses, the proportions of horses that returned to racing were analyzed, and career longevity was determined. Among 85 racing Thoroughbreds that underwent colic surgery, 31 (36%) had primarily small intestinal lesions, of which 11 underwent resection; 54 (64%) had large intestinal lesions, of which 2 underwent resection. Fifty-nine of 85 (69%) horses that underwent colic surgery returned to racing after a 6-month recovery period versus 125 of 170 (73%) reference horses (OR, 0.81). In the 36-month postoperative period, reference horses earned a mean of $7,866 more, had a mean of 0.26 more starts, and had mean earnings per start of $29 more than horses that underwent surgery. Horses that underwent surgery did not have different career lengths than reference horses. Horses that underwent colic surgery did not have a significant reduction in measures of performance or career length, compared with a reference cohort.


Differential function of the NACHT-LRR (NLR) members Nod1 and Nod2 in arthritis.
The pathogenesis of chronic joint inflammation remains unclear, although the involvement of pathogen recognition receptors has been suggested recently. In the present article, we describe the role of two members of the NACHT-LRR (NLR) family, Nod1 (nucleotide-binding oligomerization domain) and Nod2 in a model of acute joint inflammation induced by intraarticular injection of Streptococcus pyogenes cell wall fragments. Here, we show that Nod2 deficiency resulted in reduced joint inflammation and protection against early cartilage damage. In contrast, Nod1 gene-deficient mice developed enhanced joint inflammation with concomitant elevated levels of proinflammatory cytokines and cartilage damage, consistent with a model in which Nod1 controls the inflammatory reaction. To explore whether the different function of Nod1 and Nod2 occurs also in humans, we exposed peripheral blood mononuclear cells (PBMCs) carrying either Nod1ins/del or Nod2fs mutation with SCW fragments in vitro. Production of both TNFalpha and IL-1beta was clearly impaired in PBMCs carrying the Nod2fs compared with PBMCs isolated from healthy controls. In line with results in Nod1 gene-deficient mice, PBMCs from individuals bearing a newly described Nod1 mutation produced enhanced levels of proinflammatory cytokines after 24-h stimulation with SCW fragments. These data indicate that the NLR family members Nod1 and Nod2 have different functions in controlling inflammation, and that intracellular Nod1-Nod2 interactions may determine the severity of arthritis in this experimental model. Whether a distorted balance between the function of Nod1 and/or Nod2 is involved in the pathogenesis of human autoinflammatory or autoimmune disease, such as rheumatoid arthritis, remains to be elucidated.


Effects of angiotensin (1-7) upon right ventricular function in experimental rat pulmonary embolism.
Right ventricular (RV) dysfunction contributes to poor clinical prognosis after pulmonary embolism (PE). The present studies evaluate the effects of angiotensin (1-7) (ANG (1-7)) upon RV function during experimental PE in rats. Circulating ANG II increased 8-fold 6 hr after PE (47±13 PE vs. 6±3 pg/mL, control, p<0.05). ACE2 protein was uniformly localized in the RV myocardium of control rats, but showed a patchy distribution with some cells devoid of stain after 6 or 18 hr of PE. RV function decreased 18 hr after PE compared with control treated animals (19±4 vs. 41±1 mmHg, respectively, p<0.05; 669±98 vs. 1354±77 mmHg/sec, respectively, p<0.05), while left ventricular function (LV) was not significantly changed. Animals treated with ANG (1-7) during PE showed improved RV +dP/dt and peak systolic pressure development to values not significantly different from control animals. Protection of RV function by ANG (1-7) was associated with improved arterial blood sO2, base excess and pH. Supplemental delivery of ANG (1-7) reduced the development of RV dysfunction, suggesting a novel approach to protecting RV function in the setting of acute experimental PE.


Carnosic Acid Alleviates Levodopa-Induced Dyskinesia and Cell Death in 6-Hydroxydopamine-lesioned Rats and in SH-SY5Y Cells.
The present study investigated the impact of carnosic acid (CA) from rosemary on the levodopa (L-dopa)-induced dyskinesia (LID) in rats treated with 6-hydroxydopamine (6-OHDA). To establish the model of LID, 6-OHDA-lesioned rats were injected intraperitoneally with 30 mg/kg L-dopa once a day for 36 days. Rats were daily administrated with 3 or 15 mg/kg CA by oral intubation prior to L-dopa injection for 4 days. Rats pretreated with CA had reduced L-dopa-induced abnormal involuntary movements (AIMs) and ALO scores (a sum of axial, limb, and orofacial scores). Moreover, the increases of dopamine D1-receptor, p-DARPP-32, ΔFosB, p-ERK1/2, and p-c-Jun ser63, along with the decrease in p-c-Jun ser73, induced by L-dopa in 6-OHDA-treated rats were significantly reversed by pretreatment with CA. In addition, we used the model of SH-SY5Y cells to further examine the neuroprotective mechanisms of CA on L-dopa-induced cytotoxicity. SH-SY5Y cells were treated with CA for 18 h, and then co-treated with 400 μM L-dopa for the indicated time points. The results showed that pretreatment of CA attenuated the cell death and nuclear condensation induced by L-dopa. By the immunoblots, the reduction of Bcl-2, p-c-Jun ser73, and parkin and the induction of cleaved caspase 3, cleaved Poly (ADP-ribose) polymerase, p-ERK1/2, p-c-Jun ser63, and ubiquitinated protein by L-dopa were improved in cells pretreated with CA. In conclusion, CA ameliorates the development of LID via regulating the D1R signaling and prevents L-dopa-induced apoptotic cell death through modulating the ERK1/2-c-Jun and inducing the parkin. This study suggested that CA can be used to alleviate the adverse effects of LID for PD patients.


Long-range and high-precision correlation optical time-domain reflectometry utilizing an all-fiber chaotic source.
We propose a long range, high precision optical time domain reflectometry (OTDR) based on an all-fiber supercontinuum source. The source simply consists of a CW pump laser with moderate power and a section of fiber, which has a zero dispersion wavelength near the laser's central wavelength. Spectrum and time domain properties of the source are investigated, showing that the source has great capability in nonlinear optics, such as correlation OTDR due to its ultra-wide-band chaotic behavior, and mm-scale spatial resolution is demonstrated. Then we analyze the key factors limiting the operational range of such an OTDR, e. g., integral Rayleigh backscattering and the fiber loss, which degrades the optical signal to noise ratio at the receiver side, and then the guideline for counter-act such signal fading is discussed. Finally, we experimentally demonstrate a correlation OTDR with 100km sensing range and 8.2cm spatial resolution (1.2 million resolved points), as a verification of theoretical analysis.


Reconciling DLVO and non-DLVO Forces and Their Implications for Ion Rejection by a Polyamide Membrane.
Recognizing the significance of surface interactions for ion rejection and membrane fouling in nanofiltration, we revise the theories of DLVO (named after Derjaguin, Landau, Verwey, and Overbeek) and non-DLVO forces in the context of polyamide active layers. Using an atomic force microscope, surface forces between polyamide active layers and a micrometer-large and smooth silica colloid were measured in electrolyte solutions of representative monovalent and divalent ions. While the analysis of DLVO forces, accounting for surface roughness, provides how surface charge of the active layer changes with electrolyte concentration, scrutiny of non-DLVO hydration forces gives molecular insight into the composition of the membrane-solution interface. Importantly, we report an expansion of the diffuse layer at high ionic strength, consistent with the recent development of the electrical double layer theory, but in contrast to the widely accepted phenomenon of aggregation in the secondary minimum. Further, the enhanced repulsion acting on modified membranes via polyelectrolyte adsorption can be quantitatively predicted by DLVO and non-DLVO forces. This work serves to solve past misunderstandings about the interaction forces acting on nanofiltration membranes, and it provides guidance for future work on the relation between surface properties and rejection mechanisms and fouling.


Urinary and Plasma Antioxidants in Behavioral Symptoms of Individuals With Autism Spectrum Disorder.
The balance between antioxidant capacity and oxidative stress-induced free radicals may be crucial in the pathophysiological development factor of autism spectrum disorder (ASD). We measured the following urinary and plasma biomarker levels of oxidative stress and antioxidants. As urinary biomarkers, (1) hexanoyl-lysine (HEL), which is a new biomarker of oxidative stress, (2) the total antioxidant capacity (TAC), and (3) 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a product of oxidative modifications to DNA; and the plasma levels of (4) the antioxidant protein superoxide dismutase (SOD), which is the crucial defense again oxygen reactive species, and (5) transferrin and (6) ceruloplasmin, which are biomarkers of iron and copper neurotransmission and oxidant-antioxidant systems. We examined the relationship between these urinary and plasma biomarkers and behavioral symptoms in 19 individuals with ASD (mean age, 10.8 ± 5.2 years) and 10 age-matched healthy controls (mean age, 14.2 ± 7.0 years). Behavioral symptoms were estimated using the Aberrant Behavior Checklist (ABC). Urinary TAC levels were significantly lower, whereas urinary HEL levels were significantly increased in the ASD group as compared with the control group. The five ABC subscale and total scores were significantly raised in the autism group than in the control group. The results of a linear regression analysis revealed that plasma SOD levels may be a more accurate predictor of differences in ABC scores between individuals with ASD and control individuals. The present study firstly revealed the important findings that the cooperation between the urinary antioxidant TAC and plasma SOD levels may contribute to the ABC subscale scores of stereotypy. Urinary TAC activity and antioxidant protein SOD may be associated with incomplete mineral body store and antioxidant-related transcription factor and browning reactions. Consequently, a critical imbalance between TAC urinary levels and plasma SOD levels may be an important contributor to autistic behavioral symptoms.


Characterization and co-expression analysis of WRKY orthologs involved in responses to multiple abiotic stresses in Pak-choi (Brassica campestris ssp. chinensis).
The WRKY transcription factor is an important member of the stress-related transcription factors, which mediate diverse abiotic stresses in many plants. However, up until now, the number of WRKY members, and the regulatory mechanisms involved in abiotic stress responses in Pak-choi (Brassica campestris ssp. chinensis), remained unknown. We isolated and identified 56 full-length WRKY cDNAs from a Pak-choi stress-induced cDNA library. The 56 putative BcWRKY proteins were divided into three groups based on structural and phylogenetic analyses. A subcellular localization prediction indicated that the putative BcWRKY proteins were enriched in the nuclear region. Experiments involving BcWRKY25 and BcWRKY40 confirmed the prediction. A total of 22 BcWRKYs were differentially expressed in response to at least one stress condition (abscisic acid, cold, salinity, heat, or osmosis) tested on Pak-choi leaves, and a co-expression analysis indicated stress-inducible BcWRKYs co-regulated multiple abiotic stresses. BcWRKY33, BcWRKY40, BcWRKY53, and BcWRKY70 acted as key regulators and played dominant roles within co-regulatory networks of stress-inducible BcWRKYs. We first isolated and characterized the 56 stress-inducible WRKY transcription factor family members. A total of 22 stress-inducible BcWRKYs found in leaves can co-regulate multiple environmental stresses by integrating the potential mutual interactions of WRKYs in Pak-choi. This information will be valuable when exploring the molecular mechanisms of WRKYs in response to abiotic stresses in plants.


In vitro modeling of central nervous system myelination and remyelination.
This review aims to summarize the current techniques to study myelination and remyelination in culture systems. We attempt to put these into historical context, and to identify the strengths and weaknesses of each approach, which vary depending on the experimental question to be tested. We discuss the difficulty and importance of quantification of myelination and in particular remyelination. Finally, we provide our predictions of how these techniques will and should develop in the future.


Transcranial magnetic stimulation in sport science: a commentary.
The aim of this commentary is to provide a brief overview of transcranial magnetic stimulation (TMS) and highlight how this technique can be used to investigate the acute and chronic responses of the central nervous system to exercise. We characterise the neuromuscular responses to TMS and discuss how these measures can be used to investigate the mechanisms of fatigue in response to locomotor exercise. We also discuss how TMS might be used to study the corticospinal adaptations to resistance exercise training, with particular emphasis on the responses to shortening/lengthening contractions and contralateral training. The limited data to date suggest that TMS is a valuable technique for exploring the mechanisms of central fatigue and neural adaptation.


Cell type-dependent bimodal p53 activation engenders a dynamic mechanism of chemoresistance.
Studies of drug resistance mostly characterize genetic mutation, and we know much less about phenotypic mechanisms of drug resistance, especially at a quantitative level. p53 is an important mediator of cellular response to chemotherapy, but even p53 wild-type cells vary in drug sensitivity for unclear reasons. Here, we elucidated a new resistance mechanism to a DNA-damaging chemotherapeutic through bimodal modulation of p53 activation dynamics. By combining single-cell imaging with computational modeling, we characterized a four-component regulatory module, which generates bimodal p53 dynamics through coupled feed-forward and feedback, and found that the inhibitory strength between ATM and Mdm2 determined the differential modular output between drug-sensitive and drug-resistant cancer cell lines. We further showed that the combinatorial inhibition of Mdm2 and Wip1 was an effective strategy to alter p53 dynamics in resistant cancer cells and sensitize their apoptotic response. Our results point to p53 pulsing as a potentially druggable mechanism that mediates chemoresistance.


Immunohistochemical detection of occult lymph node metastases in non-small cell lung cancer: anatomical pathology results from Cancer and Leukemia Group B Trial 9761.
Our purpose was to study the detection of occult metastases (OM) in regional lymph nodes using immunohistochemical stain for cytokeratin, and for this study we targeted clinical stage I patients with non-small cell lung cancer. The study comprised the first 193 patients entered onto Cancer and Leukemia Group B protocol 9761. All had clinically staged T(1-2)N(0)M(0) non-small cell lung cancer, and all underwent curative resections of their primary tumors. Samples of the primary tumor and lymph nodes were taken from lymph node stations 2-12 and shipped to a central laboratory, where each lymph node was histologically processed and stained with H&E as well as with immunohistochemical stain using antibodies to cytokeratin (AE1/3). Altogether, we examined 825 lymph nodes. Whereas routine H&E staining allowed us to detect 18 positive lymph nodes, immunohistochemical staining allowed us to detect 45 positive lymph nodes (P < 0.0001). There were 28 OM [i.e., those detectable only by immunohistochemistry (IHC)], and there was 1 metastasis detected only by H&E staining. The OM included 9 OM in N1 stations and 19 OM in N2 stations. Twelve patients with OM had skip metastases. Routine H&E staining upstaged six patients to N1, and IHC added another five. Routine H&E upstaged 9 patients to N2, and IHC added another 11. We also uncovered new details about the way in which H&E detection depends on metastatic tumor burden. Specifically, for the probability of detecting metastases by H&E to exceed 0.50, the maximum diameter of the metastasis must be greater than 0.23 mm. IHC detects greater than twice as many positive regional lymph nodes as does H&E staining, and the foci of tumor it detects are significantly smaller than those detected by H&E staining.


Helicobacter pylori cagA+ strains and dissociation of gastric epithelial cell proliferation from apoptosis.
Infection with Helicobacter pylori induces chronic gastritis in virtually all infected persons, and such gastritis has been associated with an increased risk of developing gastric cancer. This risk is further enhanced with cagA+ (positive for cytotoxin-associated gene A) H. pylori strains and may be a consequence of induced gastric cell proliferation and/or alteration in apoptosis (programmed cell death) in the gastric epithelium. To determine whether the H. pylori cagA genotype and another virulence-related characteristic, the vacA (vacuolating cytotoxin A) s1a genotype, differentially affect epithelial cell proliferation, apoptosis, and the histologic parameters of inflammation and injury, we quantitated these characteristics in infected and uninfected persons. Fifty patients underwent upper gastrointestinal endoscopy, and biopsy specimens were taken. Apoptotic cells in the specimens were quantitated after terminal deoxynucleotidyl transferase labeling of DNA fragments with digoxigenin-deoxyuridine triphosphate; epithelial cell proliferation was scored by immunohistochemical analysis of the proliferation-associated antigen Ki-67. Antibodies directed against H. pylori and CagA protein were measured in the serum of patients by means of enzyme-linked immunosorbent assays. Analysis of H. pylori genomic DNA, by use of the polymerase chain reaction, was performed to determine the cagA and vacA genotypes. Acute and chronic inflammation, epithelial cell degeneration, mucin depletion, intestinal metaplasia, glandular atrophy, and vacuolation were each scored in a blinded manner. Reported P values are two-sided. Persons harboring cagA+ strains (n = 20) had significantly higher gastric epithelial proliferation scores than persons infected with cagA-strains (n = 9) or uninfected persons (n = 21) (P = .025 and P<.001, respectively), but the difference in cell proliferation between the latter two groups was not statistically significant. The number of apoptotic cells per 100 epithelial cells (apoptotic index) in persons infected with cagA+ strains was lower than in persons infected with cagA-strains (P = .05). Apoptotic indices in the cagA+ group were similar to those in the uninfected group (P = .2). Epithelial cell proliferation was significantly correlated with acute gastric inflammation, but only in the cagA+ group (r = .44; P = .006). The cagA+ and vacA s1a genotypes were found to be concordant, confirming the close relationship between these virulence-related genotypes. Gastric mucosal proliferation was significantly correlated with the severity of acute gastritis in persons infected with cagA+ vacA s1a strains of H. pylori. This increased proliferation was not accompanied by a parallel increase in apoptosis. Increased cell proliferation in the absence of a corresponding increase in apoptosis may explain the heightened risk for gastric carcinoma that is associated with infection by cagA+ vacA s1a strains of H. pylori.


Direct determination of therapeutic concentrations of lithium in serum by flow-injection analysis with atomic absorption spectroscopic detection.
In this flow-injection system for direct determination of lithium in serum by atomic absorption spectroscopy, the 10-microL sample is manually injected into a continuously flowing non-segmented stream of de-ionized water, which is pumped, via a dispersion tube, to the spectrometer's nebulizer. Controlled dispersion of the sample zone, before it is introduced into the nebulizer, produces the required sample dilution. Effects of varying the length of the dispersion tube, the flow rate, and the sample size were studied. Analytical readout is obtained, in the form of transient peaks, 5 s after sample injection. It is necessary to include physiological concentrations of sodium and potassium in the standard because each of these cations enhances the lithium absorbance signal. Analytical recovery (98.5 to 101%) and CV (about 2%) are good, and results compare well with those obtained by aspiration of prediluted samples (n = 121, r = 0.99).


[Interest of lignans in prevention and treatment of cancers].
Lignans are diphenolic compounds widely distributed in the plant kingdom. They are mainly localised in lignified tissues, seeds and roots. These molecules are involved in plant defence mechanisms, but are also interesting for human health. Flax lignans belonging to the phytoestrogens are metabolised after ingestion into enterolignans that may offer a protection against the onset and development of hormono-dependant cancers. In vitro studies based on mammalian cellular models tend to confirm their beneficial effects observed during epidemiological studies and give us insights about their mechanisms of action. The most studied lignan, podophyllotoxin, and its semi-synthetic derivatives (etoposide, teniposide, etoposide phosphate), are particularly interesting at a curative level due to their cytotoxic properties. These semi-synthetic derivatives are used in chemotherapy of lung cancer for example. However, the extensive use of these anticancer drugs will lead to the problem of podophyllotoxin supply. This molecule is currently extracted from the rhizomes and roots of an Indian species Podophyllum hexandrum which has subsequently become endangered. Strategies are investigated to obtain economically viable alternative sources of Podophyllotoxin from plants and in vitro cultures of several species. Among them, north american Podophyllum peltatum, Linum wild species, Hyptis, Anthriscus, Juniperus or Dysosma species which accumulate Podophyllotoxin or closely related derivatives, are good candidates. double dagger.


A systems approach to behavioral neurobiology: integrating psychodynamics and neuroscience in a psychiatric curriculum.
In the practice of medicine, an understanding of the biological functioning of organs and organ systems is the basis for theories of pathology and clinical practice. If psychoanalysis is to be accepted by the medical and psychiatric community, it must be based on a sophisticated understanding of the organ from which mental and emotional experiences emanate and use scientifically acceptable language. Each approach to psychotherapy has its own vocabulary for describing neuropsychological processes. Neurobiological vocabulary provides the various factions "neutral ground" upon which to carry on a multidisciplinary integrative dialogue. An understanding of behavioral neuroscience allows the therapist to look beyond the labels that spawn division and identify unifying biological principles that are described in a variety of ways in a multitude of theories. We contend that the neural network/representational approach to neurobiology views human mental experience as the result of multiple complex integrated systems, and is therefore holistic and antireductionistic in its perspective. Such a biologically informed psychotherapy facilitates integration of skill sets and flexibility in technique. With these principles in mind, the therapist can base his or her approach to the patient based on these principles rather than on devotion to one particular "school" or another. Because behavioral neuroscience supports many of the basic tenets of psychoanalytic theory, such an integrative psychotherapy would be psychodynamically informed. In this paper, we outline some of the ideas we present in our neuroscience course and how we relate biological concepts with some core principles of psychodynamics and psychotherapy.


Enhancing Sustainable Production of Fatty Acid Methyl Ester from Palm Oil Using Bio-Based Heterogeneous Catalyst: Process Simulation and Techno-Economic Analysis.
A new sustainable solid carbon catalyst has been developed for biodiesel synthesis using pyrolytic coconut shell ash (CSA). The CSA support was loaded with various amounts of potassium carbonate (K2CO3), and response surface methodology with a central composite design was used to optimize the transesterification process. The best-performing catalyst was the 30 wt % K2CO3/CSA catalyst. The optimal conditions included a catalyst loading of 3.27 wt %, methanol:oil molar ratio of 9.98:1, reaction time of 74 min, and temperature of 65 °C, resulting in an obtained biodiesel yield of 97.14%. This catalyst was reusable for up to four cycles, but a reduction in the biodiesel yield was observed due to potassium ion leaching during the recovery process. A techno-economic analysis to assess the financial viability of the project revealed a net present value of 5.16 million USD for a project lifetime of 20 years, a payback period time of 2.49 years, and an internal rate of return of 44.2%. An environmental assessment to evaluate the impact of global warming potential from the production of biodiesel revealed a lower level of carbon dioxide emission (1401.86 ton/y) than in the conventional process (1784.6 ton/y).


The in vitro genetic effects of fibrous erionite and crocidolite asbestos.
Epidemiologic evidence has recently identified an association between an endemic outbreak of pleural and peritoneal mesothelioma in the Urgup region of Turkey and exposure to zeolite fibres. This malignancy is usually associated with exposure to asbestos dusts whose mineralogical characteristics differ from those of zeolites. The present study further defines the in vitro biologic activity of erionite, a common zeolite fibre found in the Urgup region of Turkey. Both erionite and crocidolite asbestos fibres were clastogenic in synchronous Chinese hamster ovary (CHO) fibroblasts. Both fibres also altered CHO ploidy. Erionite, unlike crocidolite or Min-U-Sil quartz, caused a slight increase in sister chromatid exchanges in synchronous CHO cells. Neither erionite nor crocidolite was mutagenic in a human lymphoblastoid cell line. Erionite fibres thus produced in vitro cytogenic changes similar to those caused by asbestiform mineral dusts and, like asbestos fibres, did not induce mutations in human lymphoblastoid cells.


Effect of glucose and low oxygen tension on L-asparaginase production by a strain of Escherichia coli B.
Cultural and nutritional requirements for maximum l-asparaginase synthesis were determined. Conventional aerobic and anaerobic fermentations were not satisfactory. The former yielded larger quantities of cells containing minimal amounts of l-asparaginase, whereas the latter supplied only minute amounts of bacteria that contained an abundance of enzyme. However, the combination of these classical methods, i.e., allowing growth to proceed aerobically until the mid to late exponential phase and then forcing the facultative microbial cells toward anaerobic metabolism by static incubation, produced 2.6 international units of enzyme per ml of fermentation broth when glucose was present. Enzyme synthesis was not induced by terminating aeration-agitation in the absence of glucose, nor was it induced in the presence of glucose when aeration was continued. Use of 0.2 m phosphate buffer resulted in a constant pH near the optimum value of 7.5 during l-asparaginase formation. Addition of 0.05% l-asparagine prior to induction was also beneficial, but other amino acids or their catabolites failed to increase biosynthesis of l-asparaginase.


Silencing of STUB1 relieves osteoarthritis via inducing NRF2-mediated M2 macrophage polarization.
Shifting macrophages towards an anti-inflammatory state is key in treating osteoarthritis (OA) by reducing inflammation and tissue damage. However, the underlying mechanisms guiding this shift remain largely undefined. STUB1, an E3 ubiquitin ligase, known for its regulatory role in macrophage polarization. This study aims to explore the function and underlying action mechanisms of STUB1 in OA. An in vivo OA model was established in rats. Hematoxylin-Eosin and safranin O-fast green staining were performed to reveal the hispathological injuries in knee-joint tissues. Immunohistochemistry and flow cytometry were performed to detect the distribution of M1 and M2 macrophages. The inflammatory response (TNF-α and IL-6 levels) was evaluated by ELISA. In vitro, the interaction between STUB1 and NFR2 was determined by CO-IP and pull-down assays. After treated with LPS (an in vitro model of OA), the viability and apoptosis of chondrocytes were measured by CCK-8 and flow cytometry, respectively. Silencing STUB1 alleviated OA in rats, as indicated by reduced subchondral bone thickness, knee synovitis score, histopathological damages, and inflammatory response. STUB1 silencing also decreased M1 macrophages and increased M2 macrophages in both in vivo and in vitro settings. NRF2 was identified as a target of STUB1, with STUB1 mediating its ubiquitination. Silencing NRF2 reversed the effects of STUB1 silencing on inducing M2 macrophage polarization. Furthermore, silencing STUB1 upregulated NRF2 expression in LPS-treated chondrocytes, promoting cell viability and inhibiting apoptosis. Silencing STUB1 induces M2 macrophage polarization by inhibiting NRF2 ubiquitination, thereby contributing to the mitigation of OA.


Calpain inhibitor alleviates permanent hearing loss induced by intense noise by preventing disruption of gap junction-mediated intercellular communication in the cochlear spiral ligament.
Our previous studies demonstrated that intense noise-induced hearing loss might be at least in part due to an oxidative stress-induced decrease in the level of gap junction-composing protein connexins in the spiral ligament (SL) of the cochlear lateral wall structures in mice. Further, an in vivo exposure of mice to intense noise activates calpain in the cochlear SL. Based on these studies, we sought to determine whether a calpain inhibitor would prevent an intense noise exposure from causing hearing loss, disruption of gap junction-mediated intercellular communication (GJIC) in the SL. An exposure of mice to intense noise (8-Hz octave band noise, 110-dB sound pressure level, 1h) produced permanent hearing loss and cochlear hair cell death. The results of an ex vivo assay using gap-fluorescence recovery after photobleaching of dissected lateral wall structures revealed that the intense noise disrupted GJIC in the cochlear SL at day-7 post exposure. A prior intracochlear injection of the calpain inhibitor PD150606 significantly abolished this noise-induced hearing loss on days 5 and 7 post exposure. Similarly, PD150606 prevented noise-induced hair cell death and the GJIC disruption on day-7 post exposure. The intense noise temporarily enhanced the gene expression of calpain subtypes Capn1 and Capn2 immediately after exposure. Taken together, our data suggest that calpain inhibitor alleviated the noise-induced hearing loss, at least in part, by preventing disruption of GJIC in the cochlear SL. It possible that calpain inhibitors would be useful as a candidate of therapeutic drugs for sudden sensorineural hearing loss.


[The otoneurological symptoms in diffuse axonal brain lesion from the age aspect].
Since in the acute period of diffuse axonal craniocerebral trauma (CCT) the patient is comatose or, less frequently, soporous, only objective otoneurological signs (spontaneous nystagmus, altered caloric nystagmus, and traumatic damage to the otorhinolaryngological organs) may be revealed. The caloric nystagmus usually possesses all the signs characteristic of coma of different depth (absence of the caloric nystagmus in the absence of all reflexes, respiratory and cardiac disorders, total or partial loss of the rapid phase of the caloric nystagmus with the eye drifting and stopping in the direction of the slow phase of the nystagmus, the duration of such a reaction increases 3-4 fold on both sides, the vital functions are usually not disturbed in this syndrome). Both syndromes are manifested, as a rule, particularly distinctly in increasing brain edema. In the soporous state hyperreflexia of the caloric nystagmus from 2 sides was encountered with its sharp tonicity, occasional drifts of the eyes in the direction of the slow phase of the nystagmus at the peak of the caloric reaction, or hyperreflexia and tonicity of the caloric nystagmus in one direction was revealed in loss of the slow phase of the caloric nystagmus in the other direction. The last named was encountered in predominant edema of one of the cerebral hemispheres. Distinct correlations were noted as a rule between the features of the caloric nystagmus, the level of consciousness, and the degree of brain edema judged according to the findings of CT.(ABSTRACT TRUNCATED AT 250 WORDS)


Glucosamine regulates differentiation of a chondrogenic cell line, ATDC5.
Osteoarthritis (OA) is a slowly progressing chronic joint disease. Glucosamine (GlcN) is a saccharide that is widely used to relieve symptoms associated with OA. However, the mechanism of the effects of GlcN on articular cartilage remains unclear. We studied the effects of GlcN and its analogues, including chitin derivatives included in health supplements containing GlcN, on a chondrogenic cell line, ATDC5. We examined the effects of these saccharides on the proliferation and differentiation of ATDC5 cells. Glucosamine analogues, such as N-acetyl glucosamine and chitobiose, did not affect the proliferation or differentiation of ATDC5 cells. While GlcN did not affect the proliferation of ATDC5 cells, it inhibited their differentiation. Next, we examined whether GlcN affects mineralization and glycosaminoglycan (GAG) production by ATDC5 cells. Mineralization was markedly inhibited by addition of GlcN to the cell culture medium. Moreover, GlcN induced the formation of sulfated GAG in ATDC5. We also analyzed the mRNA levels in ATDC5 cells. GlcN reduced the mRNA levels of Smad2, Smad4 and MGP. GlcN might inhibit expression of MGP mRNA and induce the production of chondroitin sulfate in ATDC5 cells. The mechanism by which GlcN inhibits mineralization may be by regulating the expression of mRNA for the Smad2 and Smad4 chondrogenic master genes.


Relationship between urokinase-type plasminogen activator receptor and vascular endothelial growth factor expression and metastasis of gallbladder cancer.
To investigate the relationship of urokinase type plasminogen activator receptor (uPAR) and vascular endothelial growth factor (VEGF) expression with clinical and pathological characteristics of human gallbladder cancer. uPAR and VEGF expressions in 68 gallbladder cancer tissues were detected with anti-receptor immunohistochemical stain. Expression rate of uPAR was 57.4% (39/68), and VEGF 51.5% (35/68) in gallbladder cancer tissues. Expression of both uPAR and VEGF was significantly related to metastasis, but not significantly correlated with differentiation stage and size of gallbladder cancer. Expression of uPAR and VEGF may be an invasive phenotype of gallbladder cancer and indicator for predicting prognoses, and uPAR expression is significantly correlated with the expression of VEGF.


A Noisy Analog-to-Digital Converter Connects Cytosolic Calcium Bursts to Transcription Factor Nuclear Localization Pulses in Yeast.
Several examples of transcription factors that show stochastic, unsynchronized pulses of nuclear localization have been described. Here we show that under constant calcium stress, nuclear localization pulses of the transcription factor Crz1 follow stochastic variations in cytosolic calcium concentration. We find that the size of the stochastic calcium bursts is positively correlated with the number of subsequent Crz1 pulses. Based on our observations, we propose a simple stochastic model of how the signaling pathway converts a constant external calcium concentration into a digital number of Crz1 pulses in the nucleus, due to the time delay from nuclear transport and the stochastic decoherence of individual Crz1 molecule dynamics. We find support for several additional predictions of the model and suggest that stochastic input to nuclear transport may produce noisy digital responses to analog signals in other signaling systems.


Photon Field Networks for Dynamic Real-Time Volumetric Global Illumination.
Volume data is commonly found in many scientific disciplines, like medicine, physics, and biology. Experts rely on robust scientific visualization techniques to extract valuable insights from the data. Recent years have shown path tracing to be the preferred approach for volumetric rendering, given its high levels of realism. However, real-time volumetric path tracing often suffers from stochastic noise and long convergence times, limiting interactive exploration. In this paper, we present a novel method to enable real-time global illumination for volume data visualization. We develop Photon Field Networks-a phase-function-aware, multi-light neural representation of indirect volumetric global illumination. The fields are trained on multi-phase photon caches that we compute a priori. Training can be done within seconds, after which the fields can be used in various rendering tasks. To showcase their potential, we develop a custom neural path tracer, with which our photon fields achieve interactive framerates even on large datasets. We conduct in-depth evaluations of the method's performance, including visual quality, stochastic noise, inference and rendering speeds, and accuracy regarding illumination and phase function awareness. Results are compared to ray marching, path tracing and photon mapping. Our findings show that Photon Field Networks can faithfully represent indirect global illumination within the boundaries of the trained phase spectrum while exhibiting less stochastic noise and rendering at a significantly faster rate than traditional methods.


Word-list intrusion errors predict progression to mild cognitive impairment.
Preclinical Alzheimer's disease (AD) defined by a positive AD biomarker in the presence of normal cognition is presumed to precede mild cognitive impairment (MCI). Subtle cognitive deficits and cognitive inefficiencies in preclinical AD may be detected through process and error scores on neuropsychological tests in those at risk for progression to MCI. Cognitively normal participants (n = 525) from the Alzheimer's Disease Neuroimaging Initiative were followed for up to 5 years and classified as either stable normal (n = 305) or progressed to MCI (n = 220). Cox regressions were used to determine whether baseline process scores on the Rey Auditory Verbal Learning Test (AVLT; intrusion errors, learning slope, proactive interference, retroactive interference) predicted progression to MCI and a Clinical Dementia Rating (CDR) score of 1 after considering demographic characteristics, apolipoprotein E ε4 status, cerebrospinal fluid AD biomarkers, ischemia risk, mood, functional difficulty, and standard neuropsychological total test scores for the model. Baseline AVLT intrusion errors predicted progression to MCI (hazard ratio = 1.04, 95% confidence interval 1.01-1.07, p = .008) and improved model fit after the other valuable predictors were already in the model, χ2(df = 1) = 6.330, p = .012. AVLT intrusion errors also predicted progression to CDR = 1 (hazard ratio = 1.10, 95% confidence interval 1.02-1.18, p = .016) and again improved model fit, χ2(df = 1) = 4.682, p = .030. Intrusion errors on the AVLT contribute unique value for predicting progression from normal cognition to MCI and normal cognition to mild dementia (CDR = 1). Intrusion errors appear to reflect subtle change and inefficiencies in cognition that precede impairment detected by neuropsychological total scores. (PsycINFO Database Record


First-line bevacizumab plus taxane-based chemotherapy for locally recurrent or metastatic breast cancer: safety and efficacy in an open-label study in 2,251 patients.
First-line bevacizumab combined with chemotherapy significantly improves efficacy versus chemotherapy alone in human epidermal growth factor receptor 2 (HER2)-negative locally recurrent or metastatic breast cancer (LR/mBC). This large, open-label study further assesses first-line bevacizumab with taxane-based chemotherapy in routine oncology practice. Patients with HER2-negative LR/mBC, Eastern Cooperative Oncology Group (ECOG) performance status (PS) of zero to two and no prior chemotherapy for LR/mBC received bevacizumab 10 mg/kg every 2 weeks or 15 mg/kg every 3 weeks plus taxane-based chemotherapy (or other non-anthracycline chemotherapy) until disease progression, unacceptable toxicity or patient withdrawal. The primary end point was safety; time to progression (TtP) was a secondary end point. Median follow-up in 2251 treated patients was 12.7 months. Median age was 53 years and 94% of patients had ECOG PS of zero or one. Bevacizumab was most commonly administered with single-agent paclitaxel (35%), single-agent docetaxel (33%) or taxane-based combination therapy (10%). The most frequent grade ≥3 adverse event (AE) was neutropenia (5.4%). Grade ≥3 AEs previously associated with bevacizumab included hypertension (4.4%), arterial/venous thromboembolism (3.2%), proteinuria (1.7%) and bleeding (1.4%). No new bevacizumab safety signals were observed. Median TtP was 9.5 months (95% confidence interval 9.1-9.9). The study population in ATHENA was more representative of general oncology practice than populations enrolled into randomised trials, although there may have been some bias towards younger, fitter patients. The safety and efficacy of bevacizumab-taxane therapy in this large study were consistent with results from randomised first-line trials.


177Lu Labeled Cyclic Minigastrin Analogues with Therapeutic Activity in CCK2R Expressing Tumors: Preclinical Evaluation of a Kit Formulation.
Minigastrin (MG) analogues specifically target cholecystokinin-2 receptors (CCK2R) expressed in different tumors and enable targeted radiotherapy of advanced and disseminated disease when radiolabeled with a beta emitter such as 177Lu. Especially truncated MG analogues missing the penta-Glu sequence are associated with low kidney retention and seem therefore most promising for therapeutic use. Based on [d-Glu1,desGlu2-6]MG (MG11) we have designed the two cyclic MG analogues cyclo1,9[γ-d-Glu1,desGlu2-6,d-Lys9]MG (cyclo-MG1) and cyclo1,9[γ-d-Glu1,desGlu2-6,d-Lys9,Nle11]MG (cyclo-MG2). In the present work we have developed and preclinically evaluated a pharmaceutical kit formulation for the labeling with 177Lu of the two DOTA-conjugated cyclic MG analogues. The stability of the kits during storage as well as the stability of the radiolabeled peptides was investigated. A cell line stably transfected with human CCK2R and a control cell line without receptor expression were used for in vitro and in vivo studies with the radioligands prepared from kit formulations. In terms of stability 177Lu-DOTA-cyclo-MG2 showed advantages over 177Lu-DOTA-cyclo-MG1. Still, for both radioligands a high receptor-mediated cell uptake and favorable pharmacokinetic profile combining receptor-specific tumor uptake with low unspecific tissue uptake and low kidney retention were confirmed. Investigating the therapy efficacy and treatment toxicity in xenografted BALB/c nude mice a receptor-specific and comparable therapeutic effect could be demonstrated for both radioligands. A 1.7- to 2.6-fold increase in tumor volume doubling time was observed for receptor-positive tumors in treated versus untreated animals, which was 39-73% higher when compared to receptor-negative tumors. The treatment was connected with transient bone marrow toxicity and minor signs of kidney toxicity. All together the obtained results support further studies for the clinical translation of this new therapeutic approach.


Evidence for the involvement of gamma delta T cells in the immune response in Rasmussen encephalitis.
Rasmussen encephalitis (RE) is a rare neuroinflammatory disease characterized by intractable seizures and progressive atrophy on one side of the cerebrum. Perivascular cuffing and clusters of T cells in the affected cortical hemisphere are indicative of an active cellular immune response. Peripheral blood mononuclear cells (PBMCs) and brain-infiltrating lymphocytes (BILs) were isolated from 20 RE surgery specimens by standard methods, and CD3(+) T cell populations were analyzed by flow cytometry. Gamma delta T cell receptor spectratyping was carried out by nested PCR of reversed transcribed RNA extracted from RE brain tissue, followed by high resolution capillary electrophoresis. A MiSeq DNA sequencing platform was used to sequence the third complementarity determining region (CDR3) of δ1 chains. CD3(+) BILs from all of the RE brain specimens comprised both αβ and γδ T cells. The median αβ:γδ ratio was 1.9 (range 0.58-5.2) compared with a median ratio of 7.7 (range 2.7-40.8) in peripheral blood from the same patients. The αβ T cells isolated from brain tissue were predominantly CD8(+), and the majority of γδ T cells were CD4(-) CD8(-). Staining for the early activation marker CD69 showed that a fraction of the αβ and γδ T cells in the BILs were activated (median 42%; range 13-91%, and median 47%; range 14-99%, respectively). Spectratyping T cell receptor (TCR) Vδ1-3 chains from 14 of the RE brain tissue specimens indicated that the γδ T cell repertoire was relatively restricted. Sequencing δ1 chain PCR fragments revealed that the same prevalent CDR3 sequences were found in all of the brain specimens. These CDR3 sequences were also detected in brain tissue from 15 focal cortical dysplasia (FCD) cases. Neuroinflammation in RE involves both activated αβ and γδ T cells. The presence of γδ T cells with identical TCR δ1 chain CDR3 sequences in all of the brain specimens examined suggests that a non-major histocompatibility complex (MHC)-restricted immune response to the same antigen(s) is involved in the etiology of RE. The presence of the same δ1 clones in CD brain implies the involvement of a common inflammatory pathway in both diseases.


Effect of endogenous pyrogen, corticosteroids and inhibitors of prostaglandins and leukotrienes on the plasma concentrations of haptoglobin and fibrinogen in rats.
Injections of endogenous pyrogen (EP) in normal rats significantly increased plasma concentration of haptoglobin and fibrinogen while in adrenalectomized animals the same treatment was ineffective. Nevertheless when cortisone was injected simultaneously with EP into adrenalectomized rats the responses of fibrinogen and haptoglobin were restored. These results suggest that biosynthesis of fibrinogen and haptoglobin is corticosteroid-dependent. Inhibition of the cyclo-oxygenase pathway with ibuprofen or the lipoxygenase pathway with BW755C had no effect on the increase of plasma fibrinogen or haptoglobin levels stimulated by either EP or endotoxin. These data indicate that neither prostaglandins nor leukotrienes are involved in the production of these acute phase reactants induced by either stimulus.


A randomized controlled trial on the effects of blue-blocking glasses compared to partial blue-blockers on sleep outcomes in the third trimester of pregnancy.
Sleep disturbances are common in pregnancy. Blocking blue light has been shown to improve sleep and may be a suitable intervention for sleep problems during pregnancy. The present study investigated the effects of blue light blocking in the evening and during nocturnal awakenings among pregnant women on primary sleep outcomes in terms of total sleep time, sleep efficiency and mid-point of sleep. In a double-blind randomized controlled trial, 60 healthy nulliparous pregnant women in the beginning of the third trimester were included. They were randomized, using a random number generator, either to a blue-blocking glass intervention (n = 30) or to a control glass condition constituting partial blue-blocking effect (n = 30). Baseline data were recorded for one week and outcomes were recorded in the last of two intervention/control weeks. Sleep was measured by actigraphy, sleep diaries, the Bergen Insomnia Scale, the Karolinska Sleepiness Scale and the Pre-Sleep Arousal Scale. The results on the primary outcomes showed no significant mean difference between the groups at posttreatment, neither when assessed with sleep diary; total sleep time (difference = .78[min], 95%CI = -19.7, 21.3), midpoint of sleep (difference = -8.9[min], 95%CI = -23.7, 5.9), sleep efficiency (difference = -.06[%], 95%CI = -1.9, 1.8) and daytime functioning (difference = -.05[score points], 95%CI = -.33, .22), nor by actigraphy; total sleep time (difference = 13.0[min], 95%CI = -9.5, 35.5), midpoint of sleep (difference = 2.1[min], 95%CI = -11.6, 15.8) and sleep efficiency (difference = 1.7[%], 95%CI = -.4, 3.7). On the secondary outcomes, the Bergen Insomnia Scale, the Karolinska Sleepiness Scale and the Pre-Sleep Arousal Scale the blue-blocking glasses no statistically significant difference between the groups were found. Transient side-effects were reported in both groups (n = 3). The use of blue-blocking glasses compared to partially blue-blocking glasses in a group of healthy pregnant participants did not show statistically significant effects on sleep outcomes. Research on the effects of blue-blocking glasses for pregnant women with sleep-problems or circadian disturbances is warranted. The trial is registered at ClinicalTrials.gov (NCT03114072).


Identification of the Serratia marcescens hemolysin determinant by cloning into Escherichia coli.
A cosmid bank of Serratia marcescens was established from which DNA fragments were cloned into the plasmid pBR322, which conferred the chromosomally encoded hemolytic activity to Escherichia coli K-12. By transposon mutagenesis with Tn1000 and Tn5 IS50L::phoA (TnphoA), the coding region was assigned to a DNA fragment, designated hly, comprising approximately 7 kilobases. Two proteins with molecular weights of 61,000 (61K protein) and 160,000 (160K protein) were expressed by the pBR322 derivatives and by a plasmid which contained the hly genes under the control of a phage T7 promoter and the T7 RNA polymerase. When strongly overexpressed the 160K protein was released by E. coli cells into the extracellular medium concomitant with hemolytic activity. The genes encoding the 61K and the 160K proteins were transcribed in the same direction. Mutants expressing a 160K protein truncated at the carboxy-terminal end were partially hemolytic. Hemolysis was progressively inhibited by saccharides with increasing molecular weights from maltotriose (Mr 504) to maltoheptaose (Mr 1,152) and was totally abolished by dextran 4 (Mr 4,000). This result and the observed influx of [14C]sucrose into erythrocytes in the presence of hemolytic E. coli transformants under osmotically protective conditions suggest the formation of defined transmembrane channels by the hemolysin.


Synthesis, structural characterisation, and cytotoxicity studies of Bi, W, and Mo containing homo- and hetero-bimetallic polyoxometalates.
Three new and different homo- and hetero-bimetallic polyoxometalate (POM) species have been synthesised by simple one-pot synthetic methods utilising naturally occurring bismite (Bi2O3) (or Bi(NO3)3·5H2O) and aryl sulfonic acids. The POM species isolated are (NH4)14[Bi2W22O76]·14H2O (1·14H2O), (NH4)[Bi(DMSO)7][Mo8O26]·H2O (2·H2O) and [(NH4)4(Mo36O108(OH)4·16H2O)]·45H2O (3·45H2O). The compounds have been characterised by X-ray crystallography, energy dispersive X-ray spectroscopy (EDX), powdered X-ray diffraction (PXRD), mass spectrometry (ESI-MS), Raman spectroscopy, thermogravimetric (TGA) and ICP analyis. In vitro cytoxicity and proliferation studies conducted on 1 and 3, highlight the low toxicity of these species.


A three-way comparative study on the efficacy of twin sol to gel systems and marketed eye drops of pefloxacin mesylate.
The authors compare the efficacy of sol to gel systems and marketed eye drops of Pefloxacin mesylate (PM) in the patients with bacterial conjunctivitis. It was an open, comparative, 3-treatment, randomized, parallel study. Formulations were tested on 15 patients with bacterial conjunctivitis. Each formulation was tested on 5 patients. Patients receiving marketed eye drops were instructed to use 2 drops, 4 times a day for 7 days. Patients receiving sol to gel were instructed to use 1 drop every 12 hours for 7 days. Pharmacodynamic parameters, based on a scale of rating, were used to assess the improvement in conjunctivitis on treatment with formulations. Conjunctival swabs were taken from eyes of patients, and viable counts were performed at days 0, 3, 5, and 7. Statistical analysis of the pharmacodynamic data indicated that both sol to gel systems used were more effective than marketed eye drops in the treatment of bacterial conjunctivitis. Results of the viable count revealed that a faster reduction in the number of colony-forming units (cfu) were obtained with both sol to gel systems, compared to marketed eye drops. It can be concluded that both sol to gel systems were superior to marketed eye drops in the treatment of bacterial conjunctivitis.


Molecular imaging of proteins in tissues by mass spectrometry.
Imaging MS (IMS) is an emerging technology that permits the direct analysis and determination of the distribution of molecules in tissue sections. Biological molecules such as proteins, peptides, lipids, xenobiotics, and metabolites can be analyzed in a high-throughput manner with molecular specificity not readily achievable through other means. Tissues are analyzed intact and thus spatial localization of molecules within a tissue is preserved. Several studies are presented that focus on the unique types of information obtainable by IMS, such as Abeta isoform distributions in Alzheimer's plaques, protein maps in mouse brain, and spatial protein distributions in human breast carcinoma. The analysis of a biopsy taken 100 years ago from a patient with amyloidosis illustrates the use of IMS with formalin-fixed tissues. Finally, the registration and correlation of IMS with MRI is presented.


A Tale of Two Tweets: What Factors Predict Forgiveness of Past Transgressions on Social Media?
As more of our lives take place online, it is increasingly common for public figures to have their current image tarnished by their mistakes and transgressions in what is often the distant past. Three experiments (N = 2,296) found that judgments of a public figure who tweeted racist statements in the past were less harsh when more time had passed and when the public figure was younger at the time of the tweet. However, politics also played a powerful role. Independent of time and age, liberals allowed less possibility of redemption for anti-Black tweets, while conservatives were less forgiving for anti-White tweets. Such partisan differences extended not only to moral judgments of the individual, but also general moral principles and participants' subjective perceptions of the situation itself, including subjective temporal distance from the tweet, the subjective age of the public figure, and the current relevance of the past statements.


Hospital-based nurse practitioner roles and interprofessional practice: a scoping review.
This scoping review provides current global understanding of the rapidly evolving nurse practitioner role within hospital settings, and considers the level of understanding of its enactment within interprofessional teamwork. Arksey and O'Malley's framework was used to explore recent primary research, reviews, and gray literature in two ways. First, hospital-based nurse practitioner literature was mapped to country of origin, and thematically summarized. Second, clearly developed and consistently defined key interprofessional concepts were identified in the interprofessional literature then conceptually mapped to the nurse practitioner studies by their operationalization. The nurse practitioner review located 103 abstracts. Twenty-nine, originating from four countries, met the inclusion criteria. The interprofessional concept review identified a total of 137 relevant abstracts, however, only ten met the inclusion criteria. Understanding the nurse practitioner role within hospital teams remains limited due to a small number of countries producing evidence, the lack of nurse practitioner role title standardization hindering consistent knowledgebase development, and limited application and inconsistent operationalization of concepts within nurse practitioner research. Research focused on role enactment is needed to understand the uniqueness of the hospital-based nurse practitioner role.


Sleep-disordered breathing as a risk factor for cerebrovascular disease: a case-control study in patients with transient ischemic attacks.
The evidence that obstructive sleep apnea/hypopnea (OSAH) is a risk factor for ischemic cerebrovascular disease is inconclusive. We explored this relationship in transient ischemic attack (TIA) patients because they are less likely than stroke patients to have OSAH as a consequence of cerebrovascular disease. We performed a case-control study among 86 patients with TIA from a hospital neurovascular clinic, matched for age (+/-5 years) and sex with controls from the referring local family practice registers. Forty-nine of the 86 matched pairs were male and the body mass index was similar among cases and controls. The primary outcome measure, the apnea/hypopnea index [AHI=number of (apneas+hypopneas)/h slept, measured during overnight polysomnography and scored blind to case-control status], was the same for cases and controls (21/hour). However, the median number of 4% desaturations during sleep was slightly greater in the cases (12/hour) than controls (6/hour, P=0.04). There were the expected associations between TIA and higher fibrinogen levels (TIA 3.3, control 3.0 g/L, P=0.01), previous myocardial infarction (TIA 22, control 6%, P=0.007), a history of ever smoking (TIA 71, control 54%, P=0.01), hypertension (TIA 51, control 21%, P=0.001), and raised cholesterol (TIA 27, control 10%, P=0.01), with a weak trend for diabetes mellitus (TIA 10, control 6%, P=0.4). OSAH does not appear to be strongly associated with TIAs.


Development of Quality Measures for Pediatric Agitation Management in the Emergency Department.
Pediatric mental health emergency department (ED) visits that involve restraints for agitation are increasing. Quality measures are used to assess and improve healthcare quality. Our objective was to develop quality measures for pediatric ED agitation management informed by multidisciplinary perspectives. A multidisciplinary panel developed quality measures for pediatric ED agitation management through the modified Delphi method. Panelists ranked measures in importance and feasibility on a 9-point scale during 2 survey rounds, with a teleconference discussion between surveys. Consensus was defined by >75% of panelists ranking a quality measure highly (≥7) in importance and a median feasibility score of ≥4. Panelists included 36 physicians, nurses, social workers, security, child life specialists, hospital data analysts, and parents. The panel reached consensus on 20 quality measures. Measures with the highest percentage of scores with importance ≥7 were related to adverse medication events, patients restrained, staff/patient injuries, reescalation plans, presence of an algorithm to standardize care, formal staff training on deescalation techniques, time to medication administration, and room safety. Twenty quality measures that incorporate multidisciplinary perspectives were developed for pediatric ED agitation management. Once operationalized and field tested, these measures may be used to assess and improve healthcare quality for pediatric agitation.


Clinical outcomes with percutaneous coronary revascularization vs coronary artery bypass grafting surgery in patients with unprotected left main coronary artery disease: A meta-analysis of 6 randomized trials and 4,686 patients.
Some but not all randomized controlled trials (RCT) have suggested that percutaneous coronary intervention (PCI) with drug-eluting stents may be an acceptable alternative to coronary artery bypass grafting (CABG) surgery for the treatment of unprotected left main coronary artery disease (ULMCAD). We therefore aimed to compare the risk of all-cause mortality between PCI and CABG in patients with ULMCAD in a pairwise meta-analysis of RCT. Randomized controlled trials comparing PCI vs CABG for the treatment of ULMCAD were searched through MEDLINE, EMBASE, Cochrane databases, and proceedings of international meetings. Six trials including 4,686 randomized patients were identified. After a median follow-up of 39 months, there were no significant differences between PCI vs CABG in the risk of all-cause mortality (hazard ratio [HR] 0.99, 95% CI 0.76-1.30) or cardiac mortality. However, a significant interaction for cardiac mortality (Pinteraction= .03) was apparent between randomization arm and SYNTAX score, such that the relative risk for mortality tended to be lower with PCI compared with CABG among patients in the lower SYNTAX score tertile, similar in the intermediate tertile, and higher in the upper SYNTAX score tertile. Percutaneous coronary intervention compared with CABG was associated with a similar long-term composite risk of death, myocardial infarction, or stroke (HR 1.06, 95% CI 0.82-1.37), with fewer events within 30 days after PCI offset by fewer events after 30 days with CABG (Pinteraction < .0001). Percutaneous coronary intervention was associated with greater rates of unplanned revascularization compared with CABG (HR 1.74, 95% CI 1.47-2.07). In patients undergoing revascularization for ULMCAD, PCI was associated with similar rates of mortality compared with CABG at a median follow-up of 39 months, but with an interaction effect suggesting relatively lower mortality with PCI in patients with low SYNTAX score and relatively lower mortality with CABG in patients with high SYNTAX score. Both procedures resulted in similar long-term composite rates of death, myocardial infarction, or stroke, with PCI offering an early safety advantage and CABG demonstrating greater durability.


An efficient strategy for evaluating similarity between time series based on Wavelet / Karhunen-Loève transforms.
The present work aims to present an innovative measure able to efficiently evaluate the similarity between two physiological time series. The proposed methodology combines the Haar wavelet decomposition, in which signals are represented as linear combinations of a set of orthogonal basis, with the Karhunen-Loève transform, that allows for the optimal reduction of that set of basis. The similarity measure is based on the Euclidean distance, but indirectly calculated through the linear combination coefficients of both time series. Moreover, an iterative scheme for computing the referred coefficients significantly decreases the computational complexity of the method that, due to its simplicity and fast execution, can be easily applicable in clinical applications, namely in computational demanding contexts such as telemonitoring environments. This strategy has been successfully implemented and validated inside HeartCycle project, applied to blood pressure signals collected by a telemonitoring platform (TEN-HMS) in the recognition of hypertension episodes.


Similarities among factors that render macrophages tumoricidal in lymphokine and interferon preparations.
Lymphokine preparations, including supernatants derived from antigen-stimulated Bacillus Calmette-Guérin-immune spleen cell cultures and normal spleen cells incubated with insoluble concanavalin A, were compared with partially purified L-cell interferon for the ability to render resting macrophages nonspecifically tumoricidal in vitro. Significant activation of macrophages by lymphokine preparations occurred at concentrations as low as 0.5 and 0.25% of the assay mixture for antigen-stimulated and concanavalin A-induced lymphokine, respectively. These end point concentrations were each determined to contain 0.3 unit of interferon per ml. Supernatants obtained from unstimulated normal spleen cells, concanavalin A-treated nu/nu spleen cells, or Bacillus Calmette-Guérin-immune spleen cells in the absence of sensitizing antigen did not enhance macrophage tumoricidal function and lacked interferon. Activation by L-cell interferon required at least 1 unit/ml. The macrophage-activating factors contained in lymphokine and interferon preparations were stable at pH 2 and at 56 degrees, but they were destroyed when heated at 80 degrees for 30 min, and were inactivated by trypsin. The data demonstrate common properties for the induction of tumoricidal macrophages by these divese preparations.


[Pneumothorax after "reversed" bungee jump].
We here present a case of pneumothorax in a 24 year-old previously healthy man who had performed an uncomplicated "reversed" bungee jump a few hours before. A high resolution CT scan of the thorax taken three weeks later was normal. The high energy produced during a "reversed" bungee jump, up to 7-8 g corresponds to the threshold value for NASA astronauts, and can cause injuries in healthy persons. In this case we believe that there is a correlation between the pneumothorax and the high energy jump. Bungee jumping is a very popular amusement, millions of jumps have been carried out since 1979, when the sport was introduced. No register and therefore no ratio of risk exists.


First experiences from Copenhagen with paediatric single photon emission computed tomography/computed tomography.
This study evaluates the diagnostic value of single photon emission computed tomographic (SPECT)/multislice computed tomographic (MSCT) fusion images compared with planar scintigraphy in children. Fifteen children [eight girls, mean age 13 years (range 2-17 years)] who were examined in the SPECT/16-MSCT scanner at the Department of Clinical Physiology, Nuclear Medicine and PET, Rigshospitalet were included. The studies and clinical indications were eight Tc-hydroxymethane diphosphonate bone scintigraphies (three bone abnormalities, three osteomyelitis, two bone tumours), one bone scintigraphy combined with In-labelled leukocyte study (osteomyelitis), three I-meta-iodobenzylguanidine scintigraphies (neuroblastoma), three In-octreotide scintigraphies (two carcinoid tumours, one Langerhans cell histiocytosis) and one Tc-dimercaptosuccinic acid scintigraphy (suspected renal transplant infarction). At the evaluation of the planar scans, the decision to perform a SPECT/16-MSCT scan was taken. A specialist in nuclear medicine read the SPECT scans and the CT scans were, if performed as high resolution or when in doubt, read by the specialist in radiology, followed by a simultaneous reading. We categorized the additional information gained from the SPECT/MSCT scan into three groups: (i) structural information gained from the CT scan, (ii) additional nuclear medicine information gained from the SPECT scan and (iii) information used for biopsy guidance. Use of a CT scan of diagnostic quality was only allowed (n = 1) after referral from the clinicians, and read in collaboration with the specialist in radiology. Fourteen of the 15 planar scans gained additional structural information from SPECT/CT. Twelve of 15 planar scans gained additional nuclear medicine information. Six studies gained specific information for biopsy guidance. SPECT/CT provided additional information in all cases. SPECT/CT in children seems to be a most valuable tool and it increases the certainty of the diagnostic work-up.


Fisetin Modulates Human Oral Squamous Cell Carcinoma Proliferation by Blocking PAK4 Signaling Pathways.
Human oral squamous cell carcinoma (OSCC) is a major cause of mortality and morbidity worldwide. There is an urgent need to identify bioactive molecules and potential target genes that could inhibit carcinogenesis for OSCC therapy. Fisetin (3,7,3',4'-tetrahydroxyflavone), a naturally occurring flavonoid, has been previously shown to have anti-proliferative activities in OSCC; however, its molecular mechanism is unknown. Colony formation, cell viability, Boyden chamber, wound healing, and tumor xenograft assays were used to detect the impact of fisetin on OSCC cells in vitro and in vivo. Western blot analysis was used to examine the corresponding protein expression. Fisetin treatment significantly inhibited proliferation and promoted apoptosis by repressing PAK4 expression. Moreover, fisetin treatment attenuated cell migration by blocking PAK4 signaling pathways. In addition, the tumor xenograft showed anti-tumor growth effects of fisetin exposure in vivo. Fisetin may represent a potential therapeutic strategy for human OSCC by targeting PAK4 signaling pathways.


Work environment and occupational health of dental hygienists: a qualitative assessment.
We sought to characterize the work environment and identify factors that influence the occupational health of dental hygienists. We conducted a qualitative analysis of dental hygiene work based on five national focus groups. We found that musculoskeletal symptoms are common, particularly after 10 years; common ergonomic problems included instruments and chairs. Important non-physical workplace problems include role ambiguity (eg, employee vs. independent practitioner), inadequate recognition, role identity (eg, distinction from dental assistants), role conflict (eg, with dentists and spousal office managers), and social isolation. Work organizational factors (eg, frequent part-time work, inadequate breaks, perception as a "second team" distinct from the dentist and dental-assistant team) impede the remediation of ergonomics and other problems. Job flexibility encourages hygienists to change work hours or location rather than deal with work conditions. Occupational health interventions should address social environment and work organization.


Complexity of trophic factor signaling in experimental autoimmune encephalomyelitis: differential expression of neurotrophic and gliotrophic factors.
Soluble factors that promote survival and differentiation of glia and neurons during development are likely to play key roles in neurodegeneration and demyelinating diseases such as multiple sclerosis (MS) and have the potential to be important therapeutic targets. We examined the effect of TrkB signaling and the expression patterns of neurotrophic and gliotrophic factors in the mouse brain in MOG-induced experimental allergic encephalomyelitis (EAE). With induction of mild disease, TrkB heterozygous mice were more severely affected compared to their wild type littermates. However, with more potent disease induction, TrkB heterozygotes fared similar to their wild type littermates, suggesting complex modulatory roles for TrkB signaling. One possible explanation for this difference is that the expression patterns of neurotrophic factors correlate with disease severity in individual mice with mild disease, but not in more severe disease. With the less potent induction in C57BL/6 mice, we found that BDNF was consistently increased at EAE onset, while the soluble gliotrophic factor neuregulin (NRG1) was increased only in the chronic phase of the disease. Treatment of these animals with glatiramer acetate (GA) to decrease disease severity resulted in lower levels of both BDNF and NRG1 expression in some mice at 35days after immunization compared to those in untreated EAE mice, but had no direct effect on these factors in the absence of EAE. Our results suggest a complex interplay between neurotrophic and gliotrophic factors in EAE that is dependent on disease stage and severity. While signaling by BDNF through TrkB is protective in mild disease, this effect was not seen in more severe disease. The late induction of NRG1 in the chronic stage of disease could also worsen disease severity through its known ability to activate microglial, inflammatory pathways. While complex, these studies begin to define underlying axoglial trophic activities that are likely involved in both disease pathogenesis and repair.


Characteristics and sources of oxygenated VOCs in Hong Kong: Implications for ozone formation.
To investigate the characteristics of oxygenated volatile organic compounds (OVOCs) and their potential contribution to ozone (O3) generation, we conducted 3-h high-resolution observations during the summertime of 2022 and the wintertime of 2021. This study focused on a total of 28 OVOCs in five different chemical classes, which were encompassed at two representative sites in Hong Kong, including a roadside and an urban area. During the summertime, the total concentrations of quantified OVOCs (∑OVOCs) were 45 ± 12 and 63 ± 20 μg m-3 at the roadside and urban sites, respectively, whereas the ∑OVOCs decreased by 31 ± 11 % and 38 ± 13 %, respectively, during the wintertime. Among the classes of OVOCs, carbonyls and alcohols were the two predominant at both sites, with relatively higher concentration levels of acetone, methanol, butanaldehyde, and acrolein. The sources of OVOCs have significant spatial and temporal characteristics. Spatially, OVOCs were predominately attributed to primary emission and background at the roadside site, whereas they were a combination of primary emission, secondary formation, and background at the urban site. Temporally, background sources dominated the summertime OVOCs, while the contribution of primary emissions increased for the wintertime OVOCs. The O3 formation potential (OFP) for the OVOCs was calculated. The OFPs were 67 ± 16 and 119 ± 31 μg m-3 at the roadside and urban sites during the summertime, whereas the winter OFPs declined 30 % at the roadside and 38 % at the urban site. The background sources of carbonyls and alcohols at the roadside and of carbonyls and acrylates in the urban area were the major contributors to the OFP. Controlling the OVOC sources from local non-combustion sources such as gasoline-fuel evaporation and volatile chemical-containing products could lead to a reduction of OVOCs in the background and subsequently mitigate the OFP. This is beneficial for local O3 reduction in Hong Kong and surrounding regions.


Language discrimination by newborns: toward an understanding of the role of rhythm.
Three experiments investigated the ability of French newborns to discriminate between sets of sentences in different foreign languages. The sentences were low-pass filtered to reduce segmental information while sparing prosodic information. Infants discriminated between stress-timed English and mora-timed Japanese (Experiment 1) but failed to discriminate between stress-timed English and stress-timed Dutch (Experiment 2). In Experiment 3, infants heard different combinations of sentences from English, Dutch, Spanish, and Italian. Discrimination was observed only when English and Dutch sentences were contrasted with Spanish and Italian sentences. These results suggest that newborns use prosodic and, more specifically, rhythmic information to classify utterances into broad language classes defined according to global rhythmic properties. Implications of this for the acquisition of the rhythmic properties of the native language are discussed.


High-avidity IgA protects the intestine by enchaining growing bacteria.
Vaccine-induced high-avidity IgA can protect against bacterial enteropathogens by directly neutralizing virulence factors or by poorly defined mechanisms that physically impede bacterial interactions with the gut tissues ('immune exclusion'). IgA-mediated cross-linking clumps bacteria in the gut lumen and is critical for protection against infection by non-typhoidal Salmonella enterica subspecies enterica serovar Typhimurium (S. Typhimurium). However, classical agglutination, which was thought to drive this process, is efficient only at high pathogen densities (≥108 non-motile bacteria per gram). In typical infections, much lower densities (100-107 colony-forming units per gram) of rapidly dividing bacteria are present in the gut lumen. Here we show that a different physical process drives formation of clumps in vivo: IgA-mediated cross-linking enchains daughter cells, preventing their separation after division, and clumping is therefore dependent on growth. Enchained growth is effective at all realistic pathogen densities, and accelerates pathogen clearance from the gut lumen. Furthermore, IgA enchains plasmid-donor and -recipient clones into separate clumps, impeding conjugative plasmid transfer in vivo. Enchained growth is therefore a mechanism by which IgA can disarm and clear potentially invasive species from the intestinal lumen without requiring high pathogen densities, inflammation or bacterial killing. Furthermore, our results reveal an untapped potential for oral vaccines in combating the spread of antimicrobial resistance.


A major outbreak of hantavirus infection in Belgium in 1995 and 1996.
Haemorrhagic fever with renal syndrome (HFRS) is a human disease characterized by flu-like symptoms, renal dysfunction, and in severe cases, haemorrhagic manifestations. The causative agents of HFRS are Hantaan (HTN), Seoul (SEO), Puumala (PUU) and Dobrava (DOB) hantaviruses. Hantavirus infections are of increasing importance in Europe. Outbreaks occur in Belgium with a 3- to 4-year interval with an increasing number of cases. We describe the largest outbreak so far in Belgium with 217 serologically and clinically confirmed cases in the period between October 1995 and December 1996. We demonstrated that the use of viral antigen derived from a local PUU-strain was able to detect significantly more sera positive for IgM in an immunofluorescence assay. Furthermore, although in some cases SEO, HTN and DOB antibody-reactivities were detected by ELISA, only PUU infections could be confirmed by neutralization test. The presence of an unknown hantavirus serotype circulating in Belgium should be considered.


Copine-7 is required for REM sleep regulation following cage change or water immersion and restraint stress in mice.
Sleep is affected by the environment. In rodents, changes in the amount of rapid eye movement sleep (REMS) can precede those of other sleep/wake stages. The molecular mechanism underlying the dynamic regulation of REMS remains poorly understood. Here, we focused on the sublaterodorsal nucleus (SLD), located in the pontine tegmental area, which plays a crucial role in the regulation of REMS. We searched for genes selectively expressed in the SLD and identified copine-7 (Cpne7), whose involvement in sleep was totally unknown. We generated Cpne7-Cre knock-in mice, which enabled both the knockout (KO) of Cpne7 and the genetic labeling of Cpne7-expressing cells. While Cpne7-KO mice exhibited normal sleep under basal conditions, the amount of REMS in Cpne7-KO mice was larger compared to wildtype mice following cage change or water immersion and restraint stress, both of which are conditions that acutely reduce REMS. Thus, it was suggested that copine-7 is involved in negatively regulating REMS under certain conditions. In addition, chemogenetically activating Cpne7-expressing neurons in the SLD reduced the amount of REMS, suggesting that these neurons negatively regulate REMS. These results identify copine-7 and Cpne7-expressing neurons in the SLD as candidate molecular or neuronal components of the regulatory system that controls REMS.


Protective effect of Rhus verniciflua Stokes extract in an experimental model of post-menopausal osteoporosis.
Post-menopausal osteoporosis (PMO) is a major global human health concern. Owing to the need for therapeutic drugs without side effects, natural extracts containing various polyphenolic compounds that may exert estrogenic effects have been studied in depth. Rhus verniciflua Stokes (RVS), which has been used as a traditional herbal medicine for centuries in Korea, was recently revealed to exert estrogenic effects attributable to its bioactive ingredients sulfuretin and butein, which have strong estrogen receptor-binding affinities. In this study, the protective potential of RVS in PMO was evaluated by using an experimental animal model of PMO, which was established by ovariectomy (OVX) of female Sprague Dawley rats. The oral administration of RVS at 20 mg/kg or 100 mg/kg for 8 weeks markedly protected against OVX-induced atrophy of the uterine tube and reversed the elevation in the ratio of serum receptor activator of nuclear factor-κB ligand to osteoprotegerin, which is a marker of disease severity. In addition, RVS inhibited OVX-induced tibia bone loss, activated osteogenic activity, and suppressed osteoclastic activity in the tibial epiphyseal plate, a region of bone remodeling. Collectively, these factors indicated that the oral intake of RVS might be beneficial for the prevention of PMO.


[Experimental infection of green monkeys with adenoassociated virus].
Primary infection and reinfection with adeno-associated virus type 4 (AAV-4) was reproduced in green monkeys experimentally infected with AAV-4 in mixture with adenovirus. Wide dissemination of the satellite virus in animals was observed. AAV-4 and its antigen were detectable 5 to 23 days after inoculation. In monkeys infected with a mixture of AAV-4 and adenovirus or with one of them the infection was accompanied by a marked fever persisting from the 5th to the 20th day after inoculation. The infected monkeys showed an intensive rise of homologous antibody titer most marked on the 10th-15th day after inoculation with AAV-4. AAV-4 and its antigen were detected in smears from conjunctival and tonsillar mucosa, rectal specimens in the time course of the infectious process, as well as from the trachea, lungs, liver, spleen, intestines and kidneys of the sacrificed monkeys. Besides, AAV-4 antigen was found in cells of the tonsils and blood leukocytes of the sacrificed monkeys. No virus or its antigen were found in the brain and heart tissues. Virions of adeno-associated virus were found by electron microscopic examinations of kidney cells of one of 3 monkeys infected with AAV-4.


Primary ovarian hydatid disease in the Kingdom of Saudi Arabia.
Human hydatid disease is caused by Echinococcus granulosus. Its distribution is world wide and it affects mainly the liver, but other organs could be involved. Primary involvement of pelvic organs is very rare. This is a case report of primary ovarian hydatid disease in a postmenopausal woman, diagnosed postoperatively. Surgical excision was adequate. Ultrasonography, particularly high frequency trans-vaginal, computed tomography scan and, more recently, magnetic resonance imaging are more frequently used in the diagnosis of Echinococcus cyst. They appear more reliable than many of the old tests of varying sensitivities. Whereas, there are anecdotal reports of obstetric and gynecological manifestations of echinococcosis from some Middle Eastern and North African countries, this is the first of such report from the Kingdom of Saudi Arabia. It is unclear why there is a lack of information about this condition among Saudi women, even though socio-cultural attitude to female involvement in sheep farming and animal husbandry is similar to that in other Arabic and Islamic countries. We endorse the recommendation that every gynecologist, radiologist and histopathologist should maintain a high index of suspicion for hydatid cyst, whenever a septate cystic pelvic mass is found.


New ways to measure intraocular pressure.
In the last 10 years, several new means to measure intraocular pressure have emerged. This review covers recent findings concerning four new technologies: the ocular response analyzer, dynamic contour tonometry, rebound tonometry and the Proview phosphene tonometer. The ocular response analyzer provides measurements of corneal biomechanics, including corneal hysteresis. Intraocular pressure readings from the ocular response analyzer have correlated well with Goldmann applanation tonometry and seem to be independent of corneal thickness in nonglaucoma patients; however, further studies are needed to determine whether this is true in glaucoma patients. Dynamic contour tonometry also appears to give pressure readings that are independent of corneal thickness. Rebound tonometry is convenient, can be used without topical anesthesia and appears to correlate well with Goldmann tonometry; however, pressure readings from rebound tonometry are not independent of corneal properties. Use of the Proview phosphene tonometer appears to decrease patient anxiety regarding their glaucoma; however, studies have not been supportive of its accuracy. Dynamic contour tonometry provides intraocular pressure readings that are less dependent on corneal properties than Goldmann applanation tonometry. Rebound tonometry appears to correlate well with Goldmann tonometry and can be used without topical anesthesia.


The relationship between cigarette smoking and dental implant failure.
This paper examines the effect of tobacco use on the failure rates of dental implants. A review of 56 dental implant patients with a total of 187 endosseous dental implants, placed over a four year period, demonstrated a significant association between increased implant failure rates and cigarette smoking with failure rates of 16.6% in smokers compared to 6.9% in non-smokers. Also implant length was shown to be a significant factor with shorter implants (< or = 10 mm) being more susceptible to failure in smokers. A chi-square test was used for data analysis. Current recommendations that should be given to implant patients who smoke are included.


Catch me if you can: bacterial effectors and plant targets.
To suppress plant defense responses and favor the establishment of disease, phytopathogenic bacteria have gained the ability to deliver effector molecules inside host cells through the type III secretion system. Inside plant cells, bacterial effector proteins may be addressed to different subcellular compartments where they are able to manipulate a variety of host cellular components and molecular functions. Here we review how the recent identification and functional characterization of plant components targeted by bacterial effectors, as well as the discovery of new pathogen recognition capabilities evolved in turn by plant cells, have significantly contributed to further our knowledge about the intricate molecular interactions that are established between plants and their invading bacteria.


Impact of intraguild predation and lambda-cyhalothrin on predation efficacy of three acarophagous predators.
This laboratory study reports the interaction of three predators found in commercial apple orchards in Quebec, Hyaliodes vitripennis (Say) (Hemiptera: Miridae), Harmonia axyridis Pallas (Coleoptera: Coccinellidae) and Amblyseius fallacis (Garman) (Acarina: Phytoseiidae). First, intraguild predation between H vitripennis and the two other predators was characterized in the absence and presence of their extraguild prey, Tetranychus urticae Koch. The results showed an asymmetrical interaction in favour of the larger predator and the levels of intraguild predation were weak for the two predatory combinations. Presence of the phytophagous mite reduced the intensity of intraguild predation in the predatory combination of H axyridis and H vitripennis. Second, the effects of intraguild predation and the application of lambda-cyhalothrin on predation efficacy of the predators were evaluated. The application of the insecticide reduced prey consumption of H vitripennis and H axyridis but did not affect that of A fallacis. Combination of predators and an insecticide application resulted in two different situations depending on the species involved: a reduced predation efficacy for the combination of H vitripennis and H axyridis due to a knockdown effect caused by the insecticide, and no effect on T urticae consumption for H vitripennis and A fallacis. It is suggested that an integrated pest management program based on H vitripennis, A fallacis and lambda-cyhalothrin may be evaluated to repress phytophagous mites in Quebec orchards.


Parent-led Behavioral Intervention for a Treatment-refusing Adult With Obsessive-Compulsive Disorder With Poor Insight and Extreme Family Accommodation.
Obsessive-compulsive disorder (OCD) with poor insight can contribute to the refusal to receive treatment, leaving the burden of care on parents or other caregivers. The case presented here involved a young adult with OCD with delusional levels of insight paired with extreme family-accommodating behaviors that had resulted in impaired quality of life and functioning for the young adult and his parents. A parent-led behavioral intervention [The Supportive Parenting for Anxious Childhood Emotions (SPACE)] that was developed for children with anxiety was adapted and utilized for a young adult with severe OCD. The case presents a treatment option for parents and caregivers of individuals with OCD who refuse treatment.