The effect of metronidazole in treating human fascioliasis.
The aim of this study was to determine the effect of metronidazole in patients who did not cure after treatment with triclabendazole, in Guilan (Northern Province of Iran). Patients, who passed fasciola egg in stool and had positive serum anti fasciola antibody (ELISA), at least three months after treatment with triclabendazole, were enrolled and received 1.5 g/day metronidazole orally for three weeks. Two months and 12 months after end of therapy, stool examination in 3 consecutive days and serum anti fasciola antibody were performed. Frequency of patients with negative serology for fasciola and/or absence of fasciola egg in stool were determined. Chi-square test was used and P value <0.05 was considered significant. Forty-six patients, 26 females and 20 males, were enrolled with mean (+/-SD) age of 34.6(+/-9.8) years. Three patients excluded because of drug side effect and poor compliance. Two months after end of therapy, stool exam became negative in 35 patients and in 31 patients became negative both in serology and stool examination. (Difference in response to treat between age groups and genders was not significant). All patients with abdominal pain became pain free after therapy. Most frequent side effects were metallic taste in 14 (30.4%), headache in 8 (17.4%) and nausea in 6 (13%). 12 months after end of therapy, 28 out of 35 patients were examined again and all were negative both in serology and egg in stool examination. Metronidazole, 1.5 g/day for 3 weeks, seems to be an effective, available, well-tolerated alternative for treatment of human fascioliasis.


Microtubule-dependent effect of phorbol ester on the contractility of cytoskeleton of cultured fibroblasts.
The effect of the tumor promoter phorbol 12-myristate 13-acetate (PMA) upon the contractility of permeabilized cell models (cytoskeletons) of mouse fibroblasts was examined. Contraction was induced by incubation of cell models in a solution containing ATP and was assessed quantitatively by measuring alterations of the area of cell model projection on the substrate. Immunofluorescence microscopy was used to assess alterations of cytoskeleton morphology in the course of permeabilization and contraction. It was found that contractility of cell models from PMA-treated fibroblasts was considerably diminished as compared with the models from control fibroblasts. ATP induced only local contraction of certain zones of actin cortex in models from PMA-treated fibroblasts; it did not induce general contraction, characteristic of control models. Normal high contractility was characteristic of the models from the cells preincubated with PMA in combination with Colcemid. PMA is a specific activator of protein kinase C, one of the key enzymes of the membrane signal-transduction pathway. It is suggested that protein kinase C regulates contractility of actin cortex and that the pathway of this regulation has a microtubule-dependent stage blocked by Colcemid.


Photochemistry of retinal chromophore in mouse melanopsin.
In mammals, melanopsin is exclusively expressed in intrinsically photosensitive retinal ganglion cells (ipRGCs), which play an important role in circadian photoentrainment and other nonimage-forming functions. These ipRGCs reside in the inner retina, far removed from the pigment epithelium, which synthesizes the 11-cis retinal chromophore used by rod and cone photoreceptors to regenerate opsin for light detection. There has been considerable interest in the identification of the melanopsin chromophore and in understanding the process of photopigment regeneration in photoreceptors that are not in proximity to the classical visual cycle. We have devised an immuno-magnetic purification protocol that allows melanopsin-expressing retinal ganglion cells to be isolated and collected from multiple mouse retinas. Using this technique, we have demonstrated that native melanopsin in vivo exclusively binds 11-cis retinal in the dark and that illumination causes isomerization to the all-trans isoform. Furthermore, spectral analysis of the melanopsin photoproduct shows the formation of a protonated metarhodopsin with a maximum absorbance between 520 and 540 nm. These results indicate that even if melanopsin functions as a bistable photopigment with photo-regenerative activity native melanopsin must also use some other light-independent retinoid regeneration mechanism to return to the dark state, where all of the retinal is observed to be in the 11-cis form.


The nature of early astroglial protection-Fast activation and signaling.
Our present review is focusing on the uniqueness of balanced astroglial signaling. The balance of excitatory and inhibitory signaling within the CNS is mainly determined by sharp synaptic transients of excitatory glutamate (Glu) and inhibitory γ-aminobutyrate (GABA) acting on the sub-second timescale. Astroglia is involved in excitatory chemical transmission by taking up i) Glu through neurotransmitter-sodium transporters, ii) K+ released due to presynaptic action potential generation, and iii) water keeping osmotic pressure. Glu uptake-coupled Na+ influx may either ignite long-range astroglial Ca2+ transients or locally counteract over-excitation via astroglial GABA release and increased tonic inhibition. Imbalance of excitatory and inhibitory drives is associated with a number of disease conditions, including prevalent traumatic and ischaemic injuries or the emergence of epilepsy. Therefore, when addressing the potential of early therapeutic intervention, astroglial signaling functions combating progress of Glu excitotoxicity is of critical importance. We suggest, that excitotoxicity is linked primarily to over-excitation induced by the impairment of astroglial Glu uptake and/or GABA release. Within this framework, we discuss the acute alterations of Glu-cycling and metabolism and conjecture the therapeutic promise of regulation. We also confer the role played by key carrier proteins and enzymes as well as their interplay at the molecular, cellular, and organ levels. Moreover, based on our former studies, we offer potential prospect on the emerging theme of astroglial succinate sensing in course of Glu excitotoxicity.


Strategies in tissue engineering and regenerative medicine.
"Strategies in Tissue Engineering": this special issue is edited by Prof. Katja Schenke-Layland and Prof. Heike Walles and covers many salient aspects of tissue engineering and regenerative medicine. The issue includes articles on Raman spectroscopy and its application in tissue engineering; bioreactor design and surface functionalization for tissue culture applications; improved method for RNA isolation from tissue samples and much more.


Non-volatile control of topological phase transition in an asymmetric ferroelectric In2Te2S monolayer.
The coupling of topological electronic states and ferroelectricity is highly desired due to their abundant physical phenomenon and potential applications in multifunctional devices. However, it is difficult to achieve such a phenomenon in a single ferroelectric (FE) monolayer because the two polarized states are topologically equivalent. Here, we demonstrate that the symmetry of polarized states can be broken by constructing a Janus structure in a FE monolayer. We illustrate such a general idea by replacing a layer of Te atoms in the In2Te3 monolayer with S atoms. Using first-principles calculations, we show that the In2Te2S monolayer has two asymmetric polarized states, which are characterized by a metal and semiconductor, respectively. Importantly, as the spin-orbit coupling is included, a band gap (50.4 meV) is created in the metallic state, resulting in a non-trivial topological phase. Thus, it proves to be a feasible method to engineer non-volatile FE control of topological order in a single-phase system. We also demonstrate the underlying physical mechanism of topological phase transition, which is unveiled to be related to the weakened intrinsic electric field resulting from charge transfer. These interesting results provide a general way to design asymmetric FE materials and shed light on their potential application in non-volatile multifunctional devices.


Unacceptable failure of the PI2® implant.
The PI2® spacer is designed for treatment of trapeziometacarpal (TM) osteoarthritis. However, the shape of this implant has raised concerns about its stability. We retrospectively investigated 45 implants in 41 patients treated for trapeziometacarpal osteoarthritis in our hospital between 2004 and 2009 who underwent trapeziectomy and insertion of a PI2® spacer. Outcome parameters included revision rates and clinical outcomes correlated with implant position and scaphometacarpal distance, assessed using standard radiographs. A total of 12 implants (27%) were removed at a median time of 10 months (interquartile range (IQR), 7-22 months). These included five dislocations and one early infection. Additionally, a further six patients underwent revision due to persistent pain. Three of these had scapho-trapezoid osteoarthritis, two had developed subluxation of the implant, and one did not show any radiographic abnormalities. A review of patient records revealed that 33 implants remained in place at a median time of 29 months (IQR, 20-57). However, of those, only 21 implants (64%) in 17 patients were available for clinical evaluation at a median follow-up of 29 months (IQR, 19-62 months). No significant differences in clinical outcomes including functional results were observed between in-place ( n = 8) and subluxated ( n = 13) implants. Due to the high revision rate (12/45), consistent with other reports in the literature, we have abandoned the use of the PI2® spacer. We recommend the establishment of a registry for evaluation of future implants. Case-series study/level IV.


Deposition and metabolism of inhaled ciclesonide in the human lung.
Ciclesonide is an inhaled corticosteroid, administered as a prodrug via a metered-dose inhaler. Following deposition in the lung, ciclesonide is hydrolysed by esterases to form the pharmacologically active metabolite desisobutyryl-ciclesonide (des-CIC). Formation of des-CIC, as well as reversible esterification of des-CIC with fatty acids, has been demonstrated in vitro. The aim of this study was to investigate the in vivo metabolism of ciclesonide in the human lung. This single-dose, open-label, nonrandomised study was performed in 20 patients undergoing planned lung surgery for treatment of malignant pulmonary lesions. Patients inhaled a single dose of 1,280 μg ciclesonide at various time-points between 2 and 24 h prior to lung tissue resection. The concentration of ciclesonide, des-CIC and fatty acid conjugates of des-CIC in tissue samples was determined. Serum samples for pharmacokinetic analysis were taken at several time-points after inhalation. The pharmacokinetics in serum indicated that the inhalation by the patients was adequate. Metabolites (des-CIC, des-CIC oleate and des-CIC palmitate) were detected in the resected central and peripheral lung tissues. A substantial portion of ciclesonide was already activated to des-CIC at the first time-point of tissue analysis. Activation of ciclesonide and formation of des-CIC fatty acid conjugates was confirmed in vivo in the human lung.


Mitochondrial function: the heart of myocardial preservation.
Over the past several decades, it has become widely recognized that the mitochondria serve an important role in energy production and transfer to myocardial cells. More recently, mitochondria have been shown to play a key role in cell-death pathways by activating mitochondrial permeability transition pore formation and causing the release of several proteins, such as cytochrome c and proapoptotic factors. Although the molecular mechanisms for this process are still under investigation, important mitochondrial adaptations have been identified that can inhibit permeability transition activation and prevent apoptosis and necrosis. Specifically, myocardial preconditioning is an intriguing adaptation by which brief ischemia and reperfusion prime the mitochondria so that a subsequent prolonged period of ischemia is better tolerated. Mitochondrial ATP-dependent potassium channels seem to play a critical role in triggering or mediating this protection. The objective of this review is to outline the role of the mitochondria in supporting myocardial energy under normal and ischemic conditions. It will also provide insight into the mechanisms by which mitochondrial signaling in preconditioning can protect the myocyte during subsequent prolonged ischemic periods.


In vitro survival and retention of infectivity of Plasmodium yoelii sporozoites over extended periods of time.
The ability to maintain sporozoites in vitro should render the biological mechanism of sporozoite infectivity amenable to experimental analysis. With this in mind, Plasmodium yoelii Py17X(NL) clone 1.1 sporozoites were incubated at 4, 24, or 37 C for 0, 8, or 24 hr in tissue culture medium M199 with 5% normal mouse serum and penicillin-streptomycin. BALB/c mice were challenged intravenously with 5,000 in vitro-incubated sporozoites and then evaluated daily for parasitemia beginning on day 3 postinoculation. Sporozoites held at 24 C remained infective up to 24 hr unlike sporozoites incubated at 4 and 37 C. We observed 100% infection in mice challenged with a minimum of 200, 40, and 1,000 sporozoites that were in vitro incubated at 24 C at times 0, 24, and 36 hr, respectively. Infectivity was also maintained for 24 hr at 24 C in RPMI-1640 with 5% normal mouse serum and penicillin-streptomycin. Injection of 5,000 or 1,000 in vitro-cultured sporozoites gave 100% infection in BALB/c mice. We have demonstrated that P. yoelii sporozoites can survive in culture for extended periods of time with no apparent adverse effects on sporozoite infectivity.


Metal-Organic Framework-Manipulated Dielectric Genes Inside Silicon Carbonitride toward Tunable Electromagnetic Wave Absorption.
Heterointerface engineering for different identifiable length scales has emerged as a key research area for obtaining materials capable of high-performance electromagnetic wave absorption; however, achieving controllable architectural and compositional complexity in nanomaterials with environmental and thermal stabilities remains challenging. Herein, metal-containing silicon carbonitride (SiCN/M) nanocomposite ceramics with multiphase heterointerfaces were in situ synthesized via coordination crosslinking, catalytic graphitization, and phase separation processes using trace amounts of metal-organic frameworks (MOFs). The results reveal that the regulation of dielectric genes by MOFs can yield considerable lattice strain and abundant lattice defects, contributing to strong interfacial and dipole polarizations. The as-prepared SiCN/M ceramics demonstrate excellent microwave absorption performance: the minimum reflection loss (RLmin ) is -72.6 dB at a thickness of only 1.5 mm and -54.1 dB at an ultralow frequency of 3.56 GHz for the SiCN/Fe ceramics and the RLmin is -55.1 dB with a broad bandwidth of 3.4 GHz at an ultralow thickness of 1.2 mm for the SiCN/CoFe ceramic. The results are expected to provide guidance for the design of future dielectric microwave absorption materials based on heterointerface engineering while offering a paradigm for developing MOF-modified SiCN nanocomposite ceramics with desirable properties.


Activity-regulating structural changes and autoantibody epitopes in transglutaminase 2 assessed by hydrogen/deuterium exchange.
The multifunctional enzyme transglutaminase 2 (TG2) is the target of autoantibodies in the gluten-sensitive enteropathy celiac disease. In addition, the enzyme is responsible for deamidation of gluten peptides, which are subsequently targeted by T cells. To understand the regulation of TG2 activity and the enzyme's role as an autoantigen in celiac disease, we have addressed structural properties of TG2 in solution by using hydrogen/deuterium exchange monitored by mass spectrometry. We demonstrate that Ca(2+) binding, which is necessary for TG2 activity, induces structural changes in the catalytic core domain of the enzyme. Cysteine oxidation was found to abolish these changes, suggesting a mechanism whereby disulfide bond formation inactivates the enzyme. Further, by using TG2-specific human monoclonal antibodies generated from intestinal plasma cells of celiac disease patients, we observed that binding of TG2 by autoantibodies can induce structural changes that could be relevant for the pathogenesis. Detailed mapping of two of the main epitopes targeted by celiac disease autoantibodies revealed that they are located adjacent to each other in the N-terminal part of the TG2 molecule.


An Intraoperative Site-specific Bone Density Device: A Pilot Test Case.
This paper reports a case of all-on-four rehabilitation where bone density at implant sites was assessed both through preoperative computed tomographic (CT) scans and using a micromotor working as an intraoperative bone density measurement device. Implant-supported rehabilitation is a predictable treatment option for tooth replacement whose success depends on the clinician's experience, the implant characteristics and location and patient-related factors. Among the latter, bone density is a determinant for the achievement of primary implant stability and, eventually, for implant success. The ability to measure bone density at the placement site before implant insertion could be important in the clinical setting. A patient complaining of masticatory impairment was presented with a plan calling for extraction of all her compromised teeth, followed by implant rehabilitation. A week before surgery, she underwent CT examination, and the bone density on the CT scans was measured. When the implant osteotomies were created, the bone density was again measured with a micromotor endowed with an instantaneous torque-measuring system. The implant placement protocols were adapted for each implant, according to the intraoperative measurements, and the patient was rehabilitated following an all-on-four immediate loading protocol. The bone density device provided valuable information beyond that obtained from CT scans, allowing for site-specific, intraoperative assessment of bone density immediately before implant placement and an estimation of primary stability just after implant insertion. Measuring jaw-bone density could help clinicians to select implant-placement protocols and loading strategies based on site-specific bone features.


Aggregation of animal lactobacilli with O157 enterohemorrhagic Escherichia coli.
The effect of selected autoaggregative lactobacilli on enterohemorragic O157 Escherichia coli was studied. A total of 27 Lactobacillus sp. strains were examined for expression of autoaggregation and cell surface hydrophobicity. Autoaggregative isolates were obtained from the crops of chickens and vaginas of calves. Aggregative activity was seen between eight autoaggregative lactobacilli and six strains of enterohemorrhagic E. coli O157. The presence of aggregation-promoting factor (apf gene) was confirmed by polymerase chain reaction (PCR). We propose that autoaggregative lactobacilli that aggregate with enterohemorrhagic E. coli can express a class of APF proteins that exhibit the function of an aggregative mediator. The results of this study suggest that APF-producing lactobacilli could represent a further mechanism in the interaction of comensal microflora with enterohemorrhagic E. coli.


Surgical repair of ileovesical fistulas: long-term complications, quality of life, and patient satisfaction.
Ileovesical fistulas (IVFs) are an uncommon complication of Crohn's disease. The aim of this study is to compare long-term surgical outcomes, assess quality of life, and quantify patient satisfaction after IVF repair. A retrospective chart review followed by a prospective survey was carried out. Survey questions focused on patient satisfaction and quality of life after repair of IVF. Fifty-one patients were identified from an administrative database. Mean follow-up was 4.3 years with a response rate of 51 per cent. At the time of the study, 0 per cent mortality and 16 per cent morbidity were recorded. No recurrence was noted. There was no statistical significance in incidence of complications between laparoscopic and open surgery. Statistically significant differences in single-stage versus multistage operations were found in postoperative day of discharge (P < 0.001) and patient satisfaction (P = 0.049). Ninety-eight per cent of patients reported extreme satisfaction with their surgery and an improvement in quality of life. A low incidence of morbidity and recurrence supports early surgical intervention in IVFs.


Fragile X chromosome in institutionalized male adults with mental retardation.
A clinical and cytogenetical study of mentally retarded male adults with an IQ of below 35 has been carried out in the Ranzan Colony for Mental Retardates, Saitama, Japan. The study showed one fragile X-positive retardate with IQ 23 in the 53 residential retarded patients, giving a hemizygote prevalence of 1.9% (1/53). Macroorchidism and elongated ears, practical markers for the clinical diagnosis of fragile X-linked mental retardation, were also detected in this 43-year-old subject with fra(X)(q27.3). He is amiable and no autistic behavior has been observed. The subject, however, has been suffering from epilepsy since childhood and has cataract in both eyes.


Unfractionated heparin reduces the anti-platelet effects of abciximab but not eptifibatide during PCI.
In 29 patients undergoing percutaneous coronary intervention (PCI), we obtained blood samples at baseline, 10 minutes after standard weight-based abciximab (n=15) or double-bolus eptifibatide (n=14) and 5 minutes after unfractionated heparin (UFH; 70 U/kg bolus). The median percent inhibition was significantly higher in the eptifibatide group compared with the abciximab group both before (96.5% [94-100] vs. 85% [77-89.5] [adenosine diphosphate; ADP]; 89.5% [84-95] vs. 59% [37.5-76.5] [thrombin receptor agonist peptide; TRAP], p<0.001 for both) and after UFH (95% [93-100] vs. 79% [68.8-87.5] [ADP]; 82% [77-93] vs. 51% [34.5-71.3] [TRAP], p<0.001 for both). Addition of UFH significantly reduced platelet inhibition in the abciximab group (85% [77-89.5] vs. 79% [68.8-87.5] [ADP]; 59% [37.5-76.5] vs. 51% [34.5-71.3] [TRAP], p<0.05 for both) but not in the eptifibatide group (96.5% [94-100] vs. 95% [93-100] [ADP]; 89.5% [84-95] vs. 82% [77-93] [TRAP], p=ns for both). Eptifibatide achieved superior platelet inhibition before but especially after UFH compared with abciximab.


An Injectable Hydrogel Platform for Sustained Delivery of Anti-inflammatory Nanocarriers and Induction of Regulatory T Cells in Atherosclerosis.
Chronic unresolved vascular inflammation is a critical factor in the development of atherosclerosis. Cardiovascular immunotherapy has therefore become a recent focus for treatment, with the objective to develop approaches that can suppress excessive inflammatory responses by modulating specific immune cell populations. A benefit of such immunomodulatory strategies is that low dosage stimulation of key immune cell populations, like antigen presenting cells, can subsequently propagate strong proliferation and therapeutic responses from effector cells. We have previously demonstrated that intravenous injections of anti-inflammatory nanocarriers provided atheroprotection that was mediated by regulatory T cells (Tregs) upregulated in lymphoid organs and atherosclerotic lesions. Here, we demonstrate an injectable filamentous hydrogel depot (FM-depot) engineered for low dosage, sustained delivery of anti-inflammatory nanocarriers. The bioactive form of vitamin D (aVD; 1, 25-Dihydroxyvitamin D3), which inhibits pro-inflammatory transcription factor NF-κB via the intracellular nuclear hormone receptor vitamin D receptor (VDR), was stably loaded into poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) filomicelles. These aVD-loaded filaments underwent morphological transitions to release monodisperse drug-loaded micelles upon oxidation. This cylinder-to-micelle transition was characterized in vitro by cryogenic transmission electron microscopy (CryoTEM) and small angle X-ray scattering (SAXS). Following crosslinking with multi-arm PEG for in situ gelation, aVD-loaded FM-depots maintained high levels of Foxp3+ Tregs in both lymphoid organs and atherosclerotic lesions for weeks following a single subcutaneous injection into ApoE-/- mice. FM-depots therefore present a customizable delivery platform to both develop and test nanomedicine-based approaches for anti-inflammatory cardiovascular immunotherapy.


Sonography of Non-neoplastic Disorders of the Hand and Wrist Tendons.
Tendon disorders commonly cause hand and wrist disability and curtail the performance of work-related duties or routine tasks. Imaging is often needed for diagnosis, but it requires knowledge of the complex anatomic structures of the tendons of the hand and wrist as well as familiarity with related disorders. This review article aims to provide medical professionals with guidelines for the sonographic assessment of the tendons of hand and wrist and related disorders. Sonographic features of tendon disorders affecting the hand and wrist are described here, specifically: infectious tenosynovitis; tendon rupture or tearing; stenosing forms of tenosynovitis such as De Quervain disease and trigger finger; intersection syndrome; insertional tendinopathy; several forms of tendinous instability such as extensor carpi ulnaris instability, climber finger, and boxer knuckle; and tendinopathy in inflammatory rheumatic diseases. Postsurgical evaluation of the hand and wrist tendons is also discussed, including the healthy and pathologic appearances of operated tendons as well as impingement from orthopedic hardware. In conclusion, sonography is effective in assessing the tendons of the hand and wrist and related disorders and represents a valuable tool for diagnosis.


Endogenous vascular hydrogen peroxide regulates arteriolar tension in vivo.
Although many studies suggested direct vasomotor effects of hydrogen peroxide (H2O2) in vitro, little is known about the vasomotor effects of H2O2 in vivo. We have generated mice overexpressing human catalase driven by the Tie-2 promoter to specifically target this transgene to the vascular tissue. Vessels of these mice (cat++) expressed significantly higher levels of catalase mRNA, protein, and activity. The overexpression was selective for vascular tissue, as evidenced by immunohistochemistry in specimens of aorta, heart, lung, and kidney. Quantification of reactive oxygen species by fluorescence signals in cat++ versus catalase-negative (catn) mice showed a strong decrease in aortic endothelium and left ventricular myocardium but not in leukocytes. Awake male cat++ at 3 to 4 months of age had a significantly lower systolic blood pressure (sBP, 102.7+/-2.2 mm Hg, n=10) compared with their transgene-negative littermates (catn, 115.6+/-2.5 mm Hg, P=0.0211) and C57BL/6 mice (118.4+/-3.06 mm Hg, n=6). Treatment with the catalase inhibitor aminotriazole increased sBP of cat++ to 117.3+/-4.3 mm Hg (P=0.0345), while having no effect in catn (118.4+/-2.4 mm Hg, n=4, P>0.05). In contrast, treatment with the NO-synthase inhibitor nitro-L-arginine methyl ester (100 mg.kg BW(-1).d(-1)) increased sBP in cat++ and C57Bl/6 to a similar extent. Likewise, phosphorylation of vasodilator-stimulated phosphoprotein in skeletal muscle, left ventricular myocardium, and lung was identical in cat++ and catn. Endothelium- and NO-dependent aortic vasodilations were unchanged in cat++. Aortic KCl contractions were significantly lower in cat++ and exogenous H2O2 (10 micromol/L)-induced vasoconstriction. These data suggest that endogenous H2O2 may act as a vasoconstrictor in resistance vessels and contribute to the regulation of blood pressure.


[Functional results of the TVT procedure: a postal questionnaire on 144 patients with a median follow-up of 20 months].
Introduction. The TVT procedure has been changed the surgical treatment of stress urinary incontinence (SUI). The aim of this study was to collect the patient's point of view. and The TVT procedure was performed to treat SUI on 144 consecutive women in our institution between May 1998 and December 2000. We have sent a postal questionnaire to all patients in order to determine subjective results on SUI and post-operative voiding difficulties. We have obtained 124 responses (86.1% of patients). The median follow-up was 20 months +/- 12 (range 8 to 38 months). The patients were "very satisfied" in 56.5% (n=70), "satisfied" in 34.6% (n=43) and "unsatisfied" in 8.9% of cases (n=11). The functional discomfort about SUI was, on a 0 to 10 visual analog scale, 7.5 +/- 2 preoperatively and 2.2 +/- 2.8 post-operatively. Only 13.7% of patients have SUI postoperatively, and then 86.3% are considered cured. Nevertheless, voiding difficulties are common after this procedure with 31.5% of patients complaining about dysuria. On 96 patients who had had mixed incontinence preoperatively, 45.8% (n=44) complaining about persistent urge symptoms. On 28 patients who had had pure SUI, 28.6% (n=8) complaining about de novo urge symptoms. The TVT procedure is an efficient treatment of stress urinary incontinence, but with numerous post-operative voiding difficulties. This conclusion justify a precise pre-operative information to the patients.


Adsorbate diffusion on transition metal nanoparticles.
Diffusion of adsorbates on transition metal nanoparticles is a precursor process for heterogeneously catalyzed reactions, and as a result, an atomistic understanding of the diffusion mechanism is very important. We systematically studied adsorption and diffusion of atomic and diatomic species (H, C, N, O, CO, and NO) on nanometer-sized Pt and Cu nanoparticles with different sizes and shapes using density functional theory calculations. We show that nanoparticles bind adsorbates more strongly than the corresponding extended single crystal metal surfaces. We find that there is a Brønsted-Evans-Polanyi-type linear correlation between the transition state energy and the initial state energy for adsorbate diffusion across the edges of Pt and Cu nanoparticles. We further show that the barrier for adsorbate diffusion across the nanoparticles edges can be estimated by the binding energy of the adsorbate on the nanoparticles. These results provide useful insights for understanding diffusion-mediated chemical reactions catalyzed by transition metal nanoparticles, which are widely used in heterogeneous catalysis.


One for all--a multi-use dialysis system for effective treatment of severe thallium intoxication.
Guided by the idea of providing a stable electrolyte composition of the dialysate, the late Bernd Tersteegen designed a machine ingeniously combining the advantages of a closed tank hemodialysis system with the efficacy and bacteriological safety of a single-pass system. Several thousand dialysis sessions have been performed with this system in the chronic hemodialysis population. Recently, highly efficient (i.e. high volume) dialysis systems have been successfully introduced for the treatment of critically ill patients in the intensive care unit as extended dialysis. Furthermore, they can also be a safer, more effective and less costly alternative to traditional extracorporeal techniques in the treatment of severe intoxication. In a case-based approach, we review the increasing use of such a system.


The phenomenology of empowerment in collective action.
Recent research has hypothesized that empowerment can arise from collective action through collective self-objectification (CSO), defined as action that actualizes participants' social identity against the power of dominant groups. Activists (N = 37) described several experiences that made them feel empowered (and disempowered). Among the various explanations they offered for these feelings, the most prominent were CSO, unity, and support (or their absence). CSO was also predictive of reports of positive emotion, although unity was the best predictor of reports of further involvement. Overall, the study suggests that actualizing one's social identity through collective action has personal as well as political significance.


Melengestrol acetate blocks the preovulatory surge of luteinizing hormone, the expression of behavioral estrus, and ovulation in beef heifers.
We tested the hypothesis that melengestrol acetate (MGA), an orally active progestin, blocks estrus and the preovulatory surge of luteinizing hormone (LH) in beef heifers. Cycling yearling Angus heifers were divided randomly into two groups: MGA-treated (n = 6) and control (n = 5). All heifers received injections of prostaglandin F2alpha (PGF) on d -25, -11, and 0 to synchronize estrus. Following the last PGF injection on d 0, heifers were fed either 0.5 mg MGA in a carrier or the MGA carrier each day for 8 d. At 4-h intervals on d 1 through 6, all heifers were observed for expression of estrous behavior, and blood samples were collected and assayed for LH. Daily blood samples were collected at 0800 on d 1 through 10 and assayed for circulating progesterone concentrations. All control heifers exhibited estrus and a preovulatory surge of LH. In each case, this was followed by increases in circulating concentrations of progesterone indicative of ovulation and normal luteal function. In contrast, none of the MGA-treated heifers exhibited estrus, LH surges, or evidence of ovulation. The results of this experiment show that MGA prevents ovulation in cattle by inhibiting the preovulatory surge of LH.


Disruption of Pediatric Emergency Department Use during the COVID-19 Pandemic.
There is evidence of substantial declines in pediatric emergency department (ED) utilization in the United States in the first several months of the coronavirus disease 2019 (COVID-19) pandemic. Less is known about whether utilization changed differentially for socioeconomically disadvantaged children. This study examined how changes in pediatric ED visits during the initial months of the COVID-19 pandemic differed by two markers of socioeconomic disadvantage: minoritized race (MR) (compared with non-Hispanic White [NHW]), and publicly insured (compared with privately insured). This study used electronic medical records from a large pediatric ED for the period January to June 2020. Three time periods in 2020 were compared with corresponding time periods in 2019. Changes in overall visits, visits for MR versus NHW children, and Medicaid-enrolled versus privately insured children were considered, and changes in the acuity mix of ED visits and share of visits resulting in inpatient admits were inspected. Compared with 2019, total ED visits declined in time period (TP) 1 and TP2 of 2020 (54.3%, 48.9%). Declines were larger for MR children (57.3%, 57.8%) compared with NHW children (50.5%, 39.3%), and Medicaid enrollees (56.5%, 52.0%) compared with privately insured (48.3%, 39.0%). The MR children group experienced steeper percentage declines in high-acuity visits and visits, resulting in inpatient admissions compared with NHW children. In contrast, there was little evidence of difference between TP0s of 2019 and 2020. The role of socioeconomic disadvantage and the potential effects on pediatric ED visits during COVID-19 is understudied. Because disadvantaged children sometimes lack access to a usual source of health care, this raises concerns about unmet health needs and worsening health disparities.


Anti-coagulation therapy following coronary endarterectomy in patient with coronary artery bypass graft.
Since there is a lack of research on postoperative anticoagulation protocol in patients undergoing coronary artery bypass graft (CABG) / coronary endarterectomy (CE), we recommend a new protocol for anticoagulation in these patients. In this double-blind randomized clinical trial study, 52 patients undergoing CABG / CE entered the study and were divided into two groups. In group 1, the patients were given warfarin(international normalized ratio (INR) between 2-3) together with 80 mg aspirin daily for 3 months. In group 2, the patients were given 75 mg plavix daily together with 80 mg aspirin daily for 3 months. We evaluated patients with electrocardiography, echocardiography and checking ceratin phosphokinase MB and troponin I in the several stages. The data were analysed SPSS Version18 software. There was no significant difference between pre and post-operative Ejection fraction in patients with plavix (P=0.21) and warfarin (P=0.316) regimen. However, wall mrotion score was significantly better in clopidogrel - aspirin patients in late (3 months) post operation (p<0.001). Since warfarin has serious hemorrhagic complications and requires closed monitoring of serum drug activity by serial INR checking, it is recommended that clopidogrel - aspirin can be the preferred alternative anticoagulation therapy in CABG / CE patients.


Trends in the leading causes of death in the United States, 1970-2002.
The decrease in overall death rates in the United States may mask changes in death rates from specific conditions. To examine temporal trends in the age-standardized death rates and in the number of deaths from the 6 leading causes of death in the United States. Analyses of vital statistics data on mortality in the United States from 1970 to 2002. The age-standardized death rate and number of deaths (coded as underlying cause) from each of the 6 leading causes of death: heart disease, stroke, cancer, chronic obstructive pulmonary disease, accidents (ie, related to transportation [motor vehicle, other land vehicles, and water, air, and space] and not related to transportation [falls, fire, and accidental posioning]), and diabetes mellitus. The age-standardized death rate (per 100,000 per year) from all causes combined decreased from 1242 in 1970 to 845 in 2002. The largest percentage decreases were in death rates from stroke (63%), heart disease (52%), and accidents (41%). The largest absolute decreases in death rates were from heart disease (262 deaths per 100,000), stroke (96 deaths per 100,000), and accidents (26 deaths per 100,000).The death rate from all types of cancer combined increased between 1970 and 1990 and then decreased through 2002, yielding a net decline of 2.7%. In contrast, death rates doubled from chronic obstructive pulmonary disease over the entire time interval and increased by 45% for diabetes since 1987. Despite decreases in age-standardized death rates from 4 of the 6 leading causes of death, the absolute number of deaths from these conditions continues to increase, although these deaths occur at older ages. The absolute number of deaths and age at death continue to increase in the United States. These temporal trends have major implications for health care and health care costs in an aging population.


Antimicrobial property of silver, silver-zinc and silver-copper incorporated soda lime glass prepared by ion exchange.
Antimicrobial glasses are potential candidate as an additive in powder form for many different applications which makes them practically and scientifically important. In this context, incorporation of silver, zinc and copper into the powdered soda lime glass was carried out by ion exchange treatment using single and dual ion containing mediums. Investigating the effect of dual incorporation of silver-zinc and silver-copper on the ion release ability and antimicrobial activity of the glass was the motivation of this study. Considering the chemical analysis results, incorporation of silver, zinc and copper to the glass was realized after the treatment. The amount of released silver was observed to be higher than zinc and copper in aqueous environment. Unvarying pH values indicated that antimicrobial efficacies of the glasses were merely due to the incorporated ions. Silver release was significantly reduced in dual imparted glasses compared to the single silver imparted glasses. According to the antimicrobial test results, glasses showed sufficient and controlled level of ion release also showed antimicrobial activity. It was deduced that dual incorporation of silver-zinc and silver-copper into the glass lowered the silver release which was still sufficient for effective antimicrobial activity and this contributes the long term activity.


Neuroendocrine responses to stimulation of the splanchnic nerves in bursts in the conscious adrenalectomized calf.
Effects of stimulation of the peripheral ends of the splanchnic nerves below behavioural threshold at either 4 or 2 Hz continuously for 10 min, and at 40 or 20 Hz for 1 s at 10 s intervals for 10 min, have been compared in conscious calves. Cardiovascular responses were apparently unaffected by the pattern of the stimulus, whereas pancreatic neuroendocrine responses were significantly enhanced by stimulation in bursts, as was the rise in mean arterial plasma glucose concentration. Release of bombesin-like immunoreactivity was substantially potentiated by intermittent stimulation at relatively high frequencies and the significance of this discovery is discussed in relation to the effects that this peptide is known to evoke in this species.


Music and physics: a cultural, interdisciplinary history.
This essay investigates the triangular exchange among physicists, musicians, and instrument makers in nineteenth-century Germany by proffering a material, cultural, and interdisciplinary history. It does so by analyzing four concrete examples of such exchanges: the relationship between musical automata and virtuosi, the reed pipe as an object of music and scientific measurement, the history of standardizing performance pitch, and the attempts to measure musical virtuosity. The goal of the essay is to suggest ways in which interdisciplinary cultural histories, which take the scientific content seriously, can be an improvement upon purely disciplinary histories.


How Do Cognitive Distortions and Substance Related Problems Affect the Relationship Between Child Maltreatment and Adolescent Suicidal Ideation?
The present study, informed by the cognitive-behavioral theory of suicide, is among the first studies to examine cognitive distortions and substance related problems as potential mediators and moderators of the relation between child maltreatment (CM) and suicidal ideation (SI) in adolescent psychiatric inpatients. The sample included 185 adolescents (71.4% female; 84% White) admitted to a psychiatric inpatient unit. Participants completed self-report measures assessing cognitive errors, negative cognitive triad, substance related problems, and SI. Participants and their parents completed a semi-structured diagnostic interview assessing CM history. In this clinical sample, we found that child maltreatment was associated with suicidal ideation only for youth with current substance abuse problems, indicating moderation. Contrary to predictions, substance related problems did not mediate the association between child maltreatment and adolescent SI. Further, cognitive errors and negative cognitive triad did not mediate or moderate the association between CM and SI. However, there were significant unique effects for both cognitive errors and negative cognitive triad on SI, suggesting that adolescents with more severe cognitive distortions report greater SI, regardless of CM history. Clinically, results suggest that practitioners should carefully screen for and address any substance misuse among victims of maltreatment to prevent clinically significant SI. Study results also suggest that interventions that incorporate cognitive restructuring may help decrease risk for severe SI in adolescent clinical samples in general.


Propagating surface plasmon resonance on microhole arrays.
Metallic thin films patterned with micrometer size triangle or hole arrays present plasmonic properties when excited in the Kretschmann configuration, that are improved in comparison to conventional thin film surface plasmon resonance (SPR). These optical properties can be tuned by varying the physical aspects of the microplasmonic structures. Triangles and microhole arrays were prepared with modified nanosphere lithography (NSL) using latex spheres of 0.65, 0.82, 1.0, 1.5, or 3.2 microm in diameter. This allowed the preparation of triangles with edge lengths between 275 to 2000 nm and microhole arrays of various periodicities, diameters, and hole depths. These microstructures were studied to understand the relationship between the physical aspects and the optical properties, such as the sensitivity, working refractive index range, spectral width of the plasmonic peaks, spectral noise, and refractive index resolution. Microhole arrays with a hole diameter equal to half the periodicity were found to combine the advantages of both localized surface plasmon resonance (LSPR) on nanoparticles and SPR on a thin film. These microhole arrays exhibited high sensitivity to refractive index (>3000 nm/RIU), sensitivity to monolayer formation (2-fold improvement compared to thin films), and excellent refractive index resolution (10(-6) RIU). Finally, a biosensor for the detection of 10 nM of immunoglobulin G (IgG) exhibited a greater response with microplasmonic materials compared to conventional thin Au films. Hence, these novel plasmonic materials exhibit a strong potential as an SPR sensing platform. They can be implemented on existing instrumentation and use detection protocols developed for current SPR sensors.


Spread of a new parasitic B chromosome variant is facilitated by high gene flow.
The B24 chromosome variant emerged several decades ago in a Spanish population of the grasshopper Eyprepocnemis plorans and is currently reaching adjacent populations. Here we report, for the first time, how a parasitic B chromosome (a strictly vertically transmitted parasite) expands its geographical range aided by high gene flow in the host species. For six years we analyzed B frequency in several populations to the east and west of the original population and found extensive spatial variation, but only a slight temporal trend. The highest B24 frequency was found in its original population (Torrox) and it decreased closer to both the eastern and the western populations. The analysis of Inter Simple Sequence Repeat (ISSR) markers showed the existence of a low but significant degree of population subdivision, as well as significant isolation by distance (IBD). Pairwise Nem estimates suggested the existence of high gene flow between the four populations located in the Torrox area, with higher values towards the east. No significant barriers to gene flow were found among these four populations, and we conclude that high gene flow is facilitating B24 diffusion both eastward and westward, with minor role for B24 drive due to the arrival of drive suppressor genes which are also frequent in the donor population.


The analysis of the causative factors and types of traumas in disabled inhabitants of rural areas in Poland.
Traumas, accidents and intoxications are one of the main medical as well as social problems of the end of the previous and the present century. The number of accidents in the rural areas has been rising for the past 20 years. Little or lack of knowledge on protection of the own health against traumas, accidents and intoxications, as well as incidents such as electrocution or drowning, is a considerable problem. The study comprised 3,853 disabled persons and was carried out on the basis of physical examination (File of medical examination, File of environmental studies, File of the disabled). There were carried out statistical analyses concerning relationships of age, gender, employment, level of education and health state. The results of the studies conducted in the years 1987-2000 testify to the fact that among numerous reasons of trauma, there predominate falls, accidents connected with operating machines and appliances, mainly electric, road accidents, blows and crushes, contact with farm animals as well as electrocution and resulting burns. The most common sequels of accidents is trauma to lower extremities, upper extremities, head, thorax, spine, multiple trauma and general contusion.


Knowledge Gaps in Biophysical Changes After Powered Robotic Exoskeleton Walking by Individuals With Spinal Cord Injury-A Scoping Review.
In addition to helping individuals with spinal cord injury (SCI) regain the ability to ambulate, the rapidly evolving capabilities of robotic exoskeletons provide an array of secondary biophysical benefits which can reduce the complications resulting from prolonged immobilization. The proposed benefits of increased life-long over-ground walking capacity include improved upper body muscular fitness, improved circulatory response, improved bowel movement regularity, and reduced pain and spasticity. Beyond the positive changes related to physical and biological function, exoskeletons have been suggested to improve SCI individuals' quality of life (QOL) by allowing increased participation in day-to-day activities. Most of the currently available studies that have reported on the impact of exoskeletons on the QOL and prevention of secondary health complications on individuals with SCI, are of small scale and are heterogeneous in nature. Moreover, few meta-analyses and reviews have attempted to consolidate the dispersed data to reach more definitive conclusions of the effects of exoskeleton use. This scoping review seeks to provide an overview on the known effects of overground exoskeleton use, on the prevention of secondary health complications, changes to the QOL, and their effect on the independence of SCI individuals in the community settings. Moreover, the intent of the review is to identify gaps in the literature currently available, and to make recommendations on focus study areas and methods for future investigations.


Hypoglycaemia in non-diabetic pregnancy.
Hypoglycaemia in non-diabetic pregnancy is rare, the majority of reported cases being due to insulinoma, acute fatty liver of pregnancy, malaria and inborn errors of metabolism. A case of hypoglycaemia in a woman with previous laparoscopic sleeve gastrectomy, and hypothalamic-pituitary-adrenal axis insufficiency in the setting of opioid dependence is presented. The timing of low interstitial glucose levels was atypical for late dumping syndrome following bariatric surgery, and a change in the woman's glucocorticoid replacement resulted in resolution of hypoglycaemic symptoms. The incidence of opioid dependence in pregnancy is increasing rapidly. Health professionals should be aware of the possibility of opioids causing hypothalamic-pituitary-adrenal axis insufficiency, and the additional mechanisms by which opioids may cause hypoglycaemia.


2-[3-(4-chloro/ethyl phenyl)propan-3-one]-5-(substituted phenyl)-1,3,4-oxadiazoles: synthesis and biological evaluation.
In the present investigation, two novel series of 2-[3-(4-chlorophenyl)propan-3-one]-5-(substituted phenyl)-1,3,4-oxadiazole and 2-[3-(4-ethylphenyl)propan-3-one]-5-(substituted phenyl)-1,3,4-oxadiazole were synthesized and tested for their antiinflammatory, analgesic, ulcerogenic and antibacterial actions. A fair number of compounds were found to have very good antiinflammatory activity in carrageenan induced rat paw edema test, while a few compounds showed significant analgesic activity in acetic acid induced writhing test. The newly synthesized compounds showed very low ulcerogenic action and moderate antibacterial action.


Habitable zones around low mass stars and the search for extraterrestrial life.
Habitable planets are likely to exist around stars not too different from the Sun if current theories about terrestrial climate evolution are correct. Some of these planets may have evolved life, and some of the inhabited planets may have evolved O2-rich atmospheres. Such atmospheres could be detected spectroscopically on planets around nearby stars using a space-based interferometer to search for the 9.6 micron band of O3. Planets with O2-rich atmospheres that lie within the habitable zone around their parent star are, in all probability, inhabited.


Fifty years of research on questionable research practises in science: quantitative analysis of co-citation patterns.
Questionable research practises (QRPs) have been the focus of the scientific community amid greater scrutiny and evidence highlighting issues with replicability across many fields of science. To capture the most impactful publications and the main thematic domains in the literature on QRPs, this study uses a document co-citation analysis. The analysis was conducted on a sample of 341 documents that covered the past 50 years of research in QRPs. Nine major thematic clusters emerged. Statistical reporting and statistical power emerged as key areas of research, where systemic-level factors in how research is conducted are consistently raised as the precipitating factors for QRPs. There is also an encouraging shift in the focus of research into open science practises designed to address engagement in QRPs. Such a shift is indicative of the growing momentum of the open science movement, and more research can be conducted on how these practises are employed on the ground and how their uptake by researchers can be further promoted. However, the results suggest that, while pre-registration and registered reports receive the most research interest, less attention has been paid to other open science practises (e.g. data sharing).


Lexical differences between working and resistance sessions in psychoanalysis.
Divided 25 psychoanalytic sessions with a single patient into 10 working sessions, 5 neutral sessions, and 10 resistance sessions on the basis of ratings by psychoanalysts. Using the Regressive Imagery Dictionary on keypunched transcripts of these sessions, significantly more primary process content and less secondary process content was found in the patient's working-session speech, as opposed to resistance-session speech. Lexical diversity was also higher during working sessions. Results are compared with those obtained with other types of verbal material and are discussed in terms of psychoanalytic views on the process of psychotherapy.


Time devours things: how impulsivity and time affect temporal decisions in pathological gamblers.
Impulsivity is associated with several psychiatric disorders in which the loss of control of a specific behavior determines the syndrome itself. One particularly interesting population characterized by reported high impulsivity and problematic decision-making are those diagnosed with pathological gambling. However the association between impulsivity and decision making in pathological gambling has been only partially confirmed until now. We tested 23 normal controls and 23 diagnosed pathological gamblers in an intertemporal choice task, as well as other personality trait measurements. Results showed that gamblers scored higher on impulsivity questionnaires, and selected a higher percentage of impatient choices (higher percentage of smaller, sooner rewards), when compared to normal controls. Moreover, gamblers were faster in terms of reaction times at selecting the smaller, sooner options and discounted rewards more rapidly over time. Importantly, regression analyses clarified that self-reported measures of impulsivity played a significant role in biasing decisions towards small but more rapidly available rewards. In the present study we found evidence for impulsivity in personality traits and decisions in pathological gamblers relative to controls. We conclude by speculating on the need to incorporate impulsivity and decision biases in the conceptualization of pathological gambling for a better understanding and treatment of this pathology.


Association of Serum Pentraxin-3 and High-Sensitivity C-Reactive Protein with the Extent of Coronary Stenosis in Patients Undergoing Coronary Angiography.
We compared factors of inflammation - high sensitivity C-reactive protein (hsCRP) and pentraxin-3 (PTX3), and we explored their relationship with coronary artery disease (CAD). Also, we tested the usefulness of hsCRP and PTX3 in the risk assessment of coronary stenosis development and the diagnostic ability of these biomarkers to detect disease severity. The study group consisted of 93 CAD patients undergoing coronary angiography. Patients were divided into CAD(0), representing subclinical stenosis, and CAD (1-3), representing significant stenosis in one, two or three vessels. We determined the concentration of lipid status parameters, hsCRP and PTX3. We found significantly lower PTX3 and hsCRP concentrations in CAD(0) than in CAD(1-3) group. Concentration of PTX3 showed an increasing trend with the increasing number of vessels affected. The area under ROC curve (AUC) for the combinations of hsCRP and PTX3 with lipid parameters had useful accuracy for detecting CAD(1-3) patients (AUC=0.770, p<0.001). PTX3 is a promising independent diagnostic marker for identifying patients with CAD, and a useful indicator of disease progression. In all the analyses PTX3 showed better performance than hsCRP. A combination of PTX3, hsCRP with the lipid status parameters provides risk stratification of the development of coronary stenosis and better classification than their individual application.


Metabolism of serine/glycine lipids by human gingival cells in culture.
Porphyromonas gingivalis produces five classes of serine/glycine lipids that are recovered in lipid extracts from periodontitis-afflicted teeth and diseased gingival tissues, particularly at sites of periodontitis. Because these lipids are recovered in diseased gingival tissues, the purpose of the present study was to evaluate the capacity of cultured human gingival fibroblasts (HGF), keratinocytes, and macrophages to hydrolyze these lipids. We hypothesize that one or more of these cell types will hydrolyze the serine/glycine lipids. The primary aim was to treat these cell types for increasing time in culture with individual highly enriched serine/glycine lipid preparations. At specified times, cells and culture media samples were harvested and extracted for hydrolysis products. The serine/glycine lipids and hydrolysis products were quantified using liquid chromatography-mass spectrometry (LC-MS) and free fatty acids were quantified using gas chromatograph-mass spectrometer. LC-MS analysis used two different mass spectrometric methods. This study revealed that treatment of HGF or macrophage (THP1) cells with lipid (L) 654 resulted in breakdown to L342 and subsequent release into culture medium. However, L654 was converted only to L567 in gingival keratinocytes. By contrast, L1256 was converted to L654 by fibroblasts and macrophages but no further hydrolysis or release into medium was observed. Gingival keratinocytes showed no hydrolysis of L1256 to smaller lipid products but because L1256 was not recovered in these cells, it is not clear what hydrolysis products are produced from L1256. Although primary cultures of gingival fibroblasts and macrophages are capable of hydrolyzing specific serine/glycine lipids, prior analysis of lipid extracts from diseased gingival tissues revealed significantly elevated levels of L1256 in diseased tissues. These results suggest that the hydrolysis of bacterial lipids in gingival tissues may reduce the levels of specific lipids, but the hydrolysis of L1256 is not sufficiently rapid to prevent significant accumulation at periodontal disease sites.


Multi-beam pulsed-laser patterning of plasmonic films using broadband diffractive optical elements.
Multi-sector broadband diffractive optical elements (DOEs) were designed and fabricated from fused silica for high-efficiency multiplexing of femtosecond and nanosecond Gaussian laser beams into multiple (up to one 100) optically tunable microbeams with increased high-numerical aperture (NA) focal depths. Various DOE-related issues, such as high-NA laser focusing, laser pulsewidth, and DOE symmetry-dependent heat conduction effects, as well as the corresponding spatial resolution, were discussed in the context of high-throughput laser patterning. The increased focal depths provided by such DOEs, their high multiplexing efficiency and damage threshold, as well as easy-to-implement optical shaping of output microbeams provide advanced opportunities for direct, mask-free, and vacuum-free high-throughput subtractive (ablative) and displacive pulsed-laser patterning of various nanoplasmonic films for surface-enhanced spectroscopy, sensing, and light control.


Nanofibrous Membrane Dressings Loaded With Sodium Hydrogen Sulfide/Endothelial Progenitor Cells Promote Wound Healing.
Hydrogen sulfide (H2S) has been identified as an important gasotransmitter. H2S donor can release H2S sustained and is used as wound dressing. Endothelial progenitor cells (EPCs), given their regenerative ability, have also been reported to enhance wound healing. However, effective drug carriers are missing for the clinical application of H2S and EPCs. In this study, we investigated a novel drug carrier nanofibrous membrane, which was prepared by blending the recombinant spider silk protein (rMaSp) and sodium hydrogen sulfide (NaHS) by electrospun. Our results show that the rMaSp/NaHS nanofibrous membrane is associated with high hemocompatibility and cytocompatibility and is capable of stably releasing H2S for a long period of time. We also tested the rMaSp/NaHS membrane loaded with EPCs in an in vivo cutaneous wound model. We showed that the rMaSp/NaHS/EPC system significantly enhances wound regeneration efficiency as compared to rMaSp membrane and rMaSp/NaHS membrane. This study provides key evidence supporting the clinical application of nanofibrous membrane in the field of skin tissue regeneration.


Ecological characterization of a tropical myxomycete assemblage--Maquipucuna Cloud Forest Reserve, Ecuador.
The assemblage of myxomycetes (plasmodial slime molds) associated with cloud forests of the Maquipucuna Cloud Forest Reserve in the western Andes was investigated. Within three study sites located along a gradient extending from 1200 to 2700 m above sea level, a clear pattern of decreasing myxomycete diversity and productivity with elevation was apparent. As such, these data conform to the pattern of "reverse diversity" for myxomycetes in the neotropics, with higher diversity for less mesic forest types than for more mesic forest types. Canonical correspondence analysis of myxomycete abundances in relation to microhabitat parameters revealed three major ecological assemblages: wood-, litter- and inflorescence-inhabiting species. All three assemblages include a number of specialized species, with the assemblage associated with litter being the most diverse and the one associated with inflorescences being the most distinctive. In addition, samples from the microhabitat represented by the cover of epiphyllic liverworts on living leaves regularly produce myxomycetes in moist chamber culture but with few sporocarps and no evidence of any specialized species. At least near ground level, bark-inhabiting (corticolous) myxomycetes are uncommon in the cloud forests sampled in the present study.


Engineered vaginal lactobacillus strain for mucosal delivery of the human immunodeficiency virus inhibitor cyanovirin-N.
Women are at significant risk of human immunodeficiency virus (HIV) infection, with the cervicovaginal mucosa serving as a major portal for virus entry. Female-initiated preventatives, including topical microbicides, are urgently needed to help curtail the HIV/AIDS pandemic. Here we report on the development of a novel, live microbicide that employs a natural vaginal strain of Lactobacillus jensenii engineered to deliver the potent HIV inhibitor cyanovirin-N (CV-N). To facilitate efficient expression of CV-N by this bacterium, the L. jensenii 1153 genome was sequenced, allowing identification of native regulatory elements and sites for the chromosomal integration of heterologous genes. A CV-N expression cassette was optimized and shown to produce high levels of structurally intact CV-N when expressed in L. jensenii. Lactobacillus-derived CV-N was capable of inhibiting CCR5-tropic HIV(BaL) infectivity in vitro with a 50% inhibitory concentration of 0.3 nM. The CV-N expression cassette was stably integrated as a single copy into the bacterial chromosome and resolved from extraneous plasmid DNA without adversely affecting the bacterial phenotype. This bacterial strain was capable of colonizing the vagina and producing full-length CV-N when administered intravaginally to mice during estrus phase. The CV-N-producing Lactobacillus was genetically stable when propagated in vitro and in vivo. This work represents a major step towards the development of an inexpensive yet durable protein-based microbicide to block the heterosexual transmission of HIV in women.


Anti‑fibrotic effect of Sedum sarmentosum Bunge extract in kidneys via the hedgehog signaling pathway.
Sedum sarmentosum Bunge (SSBE) is a perennial plant widely distributed in Asian countries, and its extract is traditionally used for the treatment of certain inflammatory diseases. Our previous studies demonstrated that SSBE has marked renal anti‑fibrotic effects. However, the underlying molecular mechanisms remain to be fully elucidated. The present study identified that SSBE exerts its inhibitory effect on the myofibroblast phenotype and renal fibrosis via the hedgehog signaling pathway in vivo and in vitro. In rats with unilateral ureteral obstruction (UUO), SSBE administration reduced kidney injury and alleviated interstitial fibrosis by decreasing the levels of transforming growth factor (TGF)‑β1 and its receptor, and inhibiting excessive accumulation of extracellular matrix (ECM) components, including type I and III collagens. In addition, SSBE suppressed the expression of proliferating cell nuclear antigen, and this anti‑proliferative activity was associated with downregulation of hedgehog signaling activity in SSBE‑treated UUO kidneys. In cultured renal tubular epithelial cells (RTECs), recombinant TGF‑β1 activated hedgehog signaling, and resulted in induction of the myofibroblast phenotype. SSBE treatment inhibited the activation of hedgehog signaling and partially reversed the fibrotic phenotype in TGF‑β1‑treated RTECs. Similarly, aristolochic acid‑mediated upregulated activity of hedgehog signaling was reduced by SSBE treatment, and thereby led to the abolishment of excessive ECM accumulation. Therefore, these findings suggested that SSBE attenuates the myofibroblast phenotype and renal fibrosis via suppressing the hedgehog signaling pathway, and may facilitate the development of treatments for kidney fibrosis.


Inferring single cell expression profiles from overlapped pooling sequencing data with compressed sensing strategy.
Though single cell RNA sequencing (scRNA-seq) technologies have been well developed, the acquisition of large-scale single cell expression data may still lead to high costs. Single cell expression profile has its inherent sparse properties, which makes it compressible, thus providing opportunities for solutions. Here, by computational simulation as well as experiment of 54 single cells, we propose that expression profiles can be compressed from the dimension of samples by overlapped assigning each cell into plenty of pools. And we prove that expression profiles can be inferred from these pool expression data with overlapped pooling design and compressed sensing strategy. We also show that by combining this approach with plate-based scRNA-seq measurement, it can maintain its superiorities in gene detection sensitivity and individual identity and recover the expression profile with high precision, while saving about half of the library cost. This method can inspire novel conceptions on the measurement, storage or computation improvements for other compressible signals in many biological areas.


Disentangling the Neural Basis of Cognitive Behavioral Therapy in Psychiatric Disorders: A Focus on Depression.
Background: Major depressive disorder (MDD) stands among the most frequent psychiatric disorders. Cognitive behavioral therapy (CBT) has been shown to be effective for treating depression, yet its neural mechanisms of action are not well elucidated. The objective of this work is to assess the available neuroimaging studies exploring CBT's effects in adult patients with MDD. Methods: Computerized databases were consulted till April 2018 and a research was conducted according to PRISMA guidelines in order to identify original research articles published at any time in English and French languages on this topic. Results: Seventeen studies were identified. Only one study was randomized comparing CBT to pharmacological interventions, and none included an effective control. Following CBT, changes occurred in cerebral areas that are part of the fronto-limbic system, namely the cingulate cortex, prefrontal cortex and amygdala-hippocampal complex. However, the pattern of activation and connectivity in these areas varied across the studies. Conclusion: A considerable heterogeneity exists with regard to study design, adapted CBT type and intensity, and employed neuroimaging paradigms, all of which may partly explain the difference in studies' outcomes. The lack of randomization and effective controls in most of them makes it difficult to draw formal conclusion whether the observed effects are CBT mediated or due to spontaneous recovery. Despite the observed inconsistencies and dearth of data, CBT appears to exert its anti-depressant effects mainly by modulating the function of affective and cognitive networks devoted to emotions generation and control, respectively. This concept remains to be validated in large scale randomized controlled trials.


[Protective effect of nuclear receptor related 1 (Nurr1) on nerves in rats with cerebral occlusion/reperfusion injury and its mechanism].
Objective To investigate the protective effect of nuclear receptor related 1 (Nurr1) on nerves in rats with cerebral occlusion/reperfusion injury and its mechanism. Methods Healthy male SD rats were chosen to construct the middle cerebral artery occlusion/reperfusion (MCAO/R) model. All rats were randomly divided into control group, model group, negative virus group, and Nurr1 over-expression group. Longa's modified neurological severity score, Triphenyl tetrazolium chloride (TTC) staining, and immunofluorescence histochemical staining were applied respectively to detect the neurological injury, infarct volume, and density of microtubule associated protein-2 (MAP2) positive nerve cells in rats after MCAO/R. Related kits were used to detect the activity of superoxide dismutase (SOD) and the content of malondialdehyde (MDA). The protein levels of Nurr1, tumor necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), B cell lymphoma 2 (Bcl2), and Bcl2-assaciated X protein (BAX) were detected by Western blot. Results Nurr1 over-expression improved the neurological outcome with lower modified neurological severity scores by decreasing infarct volume, content of MDA, and expressions of inflammatory mediators including TNF-α, IL-1β, and pro-apoptosis related protein BAX. Nurr1 over-expression significantly increased the density of MAP2 positive nerve cells, activity of SOD, and the expression of anti-apoptosis related protein Bcl2. Conclusion Nurr1 may alleviate the cerebral ischemic damage by resisting oxidation, reducing inflammation, and inhibiting mitochondrial apoptotic signaling pathway-mediated cell apoptosis.


Sunlight Doubles Aboveground Carbon Loss in a Seasonally Dry Woodland in Patagonia.
Photodegradation of aboveground senescent plant material (plant litter) due to exposure to solar radiation has been identified as a dominant control on carbon (C) loss in semi-arid ecosystems [1], upturning traditional models of C cycling based only on available moisture and litter quality. In addition to the photochemical mineralization of organic matter [1, 2], sunlight alters the chemistry of cell walls in plant litter [3, 4], making them more susceptible to subsequent biotic degradation [5-7]. Nevertheless, the interactive effects of sunlight exposure, climate seasonality, and biotic decomposition on C turnover remain unresolved in terrestrial ecosystems. We show here that exposure to sunlight accelerated litter decomposition in a Patagonian woodland with a marked dry summer season. Controls on initial decomposition varied seasonally from direct photochemical mineralization in the dry summer to biotic degradation in the wet winter. By manipulating sunlight received by plant litter using spectral filters that attenuated ultraviolet and short-wave visible light, we demonstrate that direct photodegradation and its legacy, associated with increased microbial access to labile carbohydrates, are responsible for the acceleration of aboveground C turnover in this Mediterranean-type climate. Across plant species and over a 2-year period, litter exposed to the full solar spectrum decomposed twice as fast as litter that received attenuated sunlight. Changes in vegetation cover or biodiversity due to projected increased drought and dry season length [8] will likely exacerbate C losses from aboveground litter due to sunlight exposure, negatively impacting the C balance in ecosystems that are particularly vulnerable to global change [9].


The effect of PEEP ventilation on hemodynamics and regional blood flow with special regard to coronary blood flow.
An experimental study was performed to evaluate the effects of positive end-expiratory pressure (PEEP) on central hemodynamics and on regional blood flow (RBF) using the radioactive microsphere (MS) method. Ten dogs with intact lungs and 10 dogs with oleic acid-induced pulmonary edema were ventilated with PEEP 10 and PEEP 20 (cmH2O). PEEP significantly reduced cardiac output (CO) by 25% at PEEP 10 and 40--50% at PEEP 20 despite volume expansion with dextran 60. RV afterload rose markedly due to a significant increase of pulmonary vascular resistance. PEEP tended to redistribute CO in favor of brain, heart and adrenals, at the expense of stomach, pancreas and thyroid glands. Hepatic artery flow was moderately reduced; renal RBF was seriously affected only when PEEP caused an extreme low-output state. RBF to the RV remained essentially unchanged, whereas RBF to the LV decreased, roughly paralleling the respective ventricular work. Nevertheless, the RV may suffer from underperfusion during PEEP, since its tension-time-index rises; this may indicate increased oxygen needs exceeding actual oxygen delivery.


Local Hartree-Fock orbitals using a three-level optimization strategy for the energy.
Using the three-level energy optimization procedure combined with a refined version of the least-change strategy for the orbitals--where an explicit localization is performed at the valence basis level--it is shown how to more efficiently determine a set of local Hartree-Fock orbitals. Further, a core-valence separation of the least-change occupied orbital space is introduced. Numerical results comparing valence basis localized orbitals and canonical molecular orbitals as starting guesses for the full basis localization are presented. The results show that the localization of the occupied orbitals may be performed at a small computational cost if valence basis localized orbitals are used as a starting guess. For the unoccupied space, about half the number of iterations are required if valence localized orbitals are used as a starting guess compared to a canonical set of unoccupied Hartree-Fock orbitals. Different local minima may be obtained when different starting guesses are used. However, the different minima all correspond to orbitals with approximately the same locality.


Analysis of epitope-specific immune responses induced by vaccination with structurally folded and unfolded recombinant Bet v 1 allergen derivatives in man.
Previously, we have constructed recombinant derivatives of the major birch pollen allergen, Bet v 1, with a more than 100-fold reduced ability to induce IgE-mediated allergic reactions. These derivatives differed from each other because the two recombinant Bet v 1 fragments represented unfolded molecules whereas the recombinant trimer resembled most of the structural fold of the Bet v 1 allergen. In this study, we analyzed the Ab (IgE, IgG subclass, IgA, IgM) response to Bet v 1, recombinant and synthetic Bet v 1-derived peptides in birch pollen allergic patients who had been vaccinated with the derivatives or adjuvant alone. Furthermore, we studied the induction of IgE-mediated skin responses in these patients using Bet v 1 and Bet v 1 fragments. Both types of vaccines induced a comparable IgG1 and IgG4 response against new sequential epitopes which overlap with the conformational IgE epitopes of Bet v 1. This response was 4- to 5-fold higher than that induced by immunotherapy with birch pollen extract. Trimer more than fragments induced also IgE responses against new epitopes and a transient increase in skin sensitivity to the fragments at the beginning of therapy. However, skin reactions to Bet v 1 tended to decrease one year after treatment in both actively treated groups. We demonstrate that vaccination with folded and unfolded recombinant allergen derivatives induces IgG Abs against new epitopes. These data may be important for the development of therapeutic as well as prophylactic vaccines based on recombinant allergens.


Efficacy of baricitinib in the treatment of rheumatoid arthritis.
although the outcome for patients with rheumatoid arthritis (ra) has improved in the past decades, adequate disease control cannot be achieved in a substantial proportion of patients. new drugs with a novel mechanism of action, may represent a valuable addition to the current armamentarium. Areas covered: This review focuses on the pharmacodynamics and pharmacokinetics of baricitinib. Furthermore, the article summarizes and comments the drug's efficacy and safety profile in RA patients. Expert opinion: Baricitinib is an oral targeted synthetic (ts) disease-modifying antirheumatic drug (DMARD) that mainly inhibits JAK1 and JAK2. Baricitinib monotherapy, or in combination with conventional synthetic (cs) DMARDs, has demonstrated its efficacy while having an acceptable safety profile in early active RA naive to DMARDs, and active RA with an inadequate response to csDMARDs and/or biologic (b)DMARDs. The future place of baricitinib in the management of RA patients will depend on several factors. However, baricitinib offer few advantages: oral administration, rapidity of action, efficacy in monotherapy and over adalimumab in one study and non-immunization. However, pending further safety data, current practice would be to start a bDMARD when the treatment target is not achieved with csDMARDs. Availability of additional long-term safety data may influence prescribing decisions.


Oncogenic K-Ras regulates proliferation and cell junctions in lung epithelial cells through induction of cyclooxygenase-2 and activation of metalloproteinase-9.
Expression of oncogenic K-Ras is frequently observed in non-small-cell lung cancer. However, oncogenic K-Ras is not sufficient to transform lung epithelial cells and requires collaborating signals that have not been defined. To examine the biological effects of K-Ras in nontransformed lung epithelial cells, stable transfectants were generated in RL-65 cells, a spontaneously immortalized lung epithelial cell line. Expression of K-Ras resulted in extracellular signal-regulated kinase (ERK) activation, which mediated induction of cyclooxygenase (COX)-2 and increased prostaglandin E(2) production. Epithelial cells expressing oncogenic K-Ras showed increased proliferation in two- and three-dimensional tissue culture and delayed formation of hollow acinar structures in three-dimensional matrigel cultures. These affects were mediated through COX-2-dependent activation of beta-catenin signaling and inhibition of apoptosis. ERK activation also led to induction of metalloproteinase (MMP)-9 and cleavage of E-cadherin at two specific sites. This resulted in partial disruption of adherens junctions as determined by decreased transepithelial resistance (TER), and disruption of E-cadherin/beta-catenin interactions. An MMP-9 inhibitor reversed the decrease in TER and inhibited beta-catenin signaling. These data indicate that although expression of oncogenic K-Ras does not transform lung epithelial cells, it alters the phenotype of the cells by increasing proliferation and decreasing cell-cell contacts characteristic of epithelial cells.


The clinical importance of the fat compartments in midfacial aging.
The recent identification of the facial fat compartments has greatly affected our understanding of midfacial aging. This article chronicles the discovery of these fat compartments including the shift of attention from a purely gravitational to a volumetric approach to facial aging and the series of methodologies attempted to ultimately define the anatomy of these compartments. The revived interest in volumetric facial rejuvenation including compartment-guided augmentation techniques is discussed. Lastly, the article discusses interesting distributional patterns noted in these fat compartments likely related to the different mechanical and biologic environments of the deep and superficial facial fat pads.


Identifying Shared Risk Genes for Asthma, Hay Fever, and Eczema by Multi-Trait and Multiomic Association Analyses.
Asthma, hay fever and eczema are three comorbid diseases with high prevalence and heritability. Their common genetic architectures have not been well-elucidated. In this study, we first conducted a linkage disequilibrium score regression analysis to confirm the strong genetic correlations between asthma, hay fever and eczema. We then integrated three distinct association analyses (metaCCA multi-trait association analysis, MAGMA genome-wide and MetaXcan transcriptome-wide gene-based tests) to identify shared risk genes based on the large-scale GWAS results in the GeneATLAS database. MetaCCA can detect pleiotropic genes associated with these three diseases jointly. MAGMA and MetaXcan were performed separately to identify candidate risk genes for each of the three diseases. We finally identified 150 shared risk genes, in which 60 genes are novel. Functional enrichment analysis revealed that the shared risk genes are enriched in inflammatory bowel disease, T cells differentiation and other related biological pathways. Our work may provide help on treatment of asthma, hay fever and eczema in clinical applications.


Long Noncoding RNA CRNDE Promotes Multiple Myeloma Cell Growth by Suppressing miR-451.
It has been determined that long noncoding RNAs (lncRNAs) are identified as a potential regulatory factor in multiple tumors as well as multiple myeloma (MM). However, the role of colorectal neoplasia differentially expressed (CRNDE) in the pathogenesis of MM remains unclear. In this study, we found that the CRNDE expression level, in MM samples and cell lines, is higher than that in the control detected by real-time qPCR, which is also closely related to tumor progression and poor survival in MM patients. Knockdown of CRNDE significantly inhibits the proliferative vitality of MM cells (U266 and RPMI-8226), induces cell cycle arrest in the G0/G1 phase, and promotes apoptosis. After being transfected with siRNA, miR-451 expression observably increases. Bioinformatics analysis and luciferase assay reveal the interaction by complementary bonding between CRNDE and miR-451. Pearson's correlation shows that CRNDE is negatively correlated to miR-451 expression in human MM samples. Subsequently, miR-451 inhibitor rescues the inhibited tumorigenesis induced by CRNDE knockdown. Our study illustrates that lncRNA CRNDE induces the proliferation and antiapoptosis capability of MM by acting as a ceRNA or molecular sponge via negatively targeting miR-451, which could act as a novel diagnostic marker and therapeutic target for MM.


Analysis of the skin of mice humanized for the immune system.
Development of new immunotherapeutic strategies relies on the ability to activate the right cells at the right place and at the right moment and on the capacity of these cells to home to the right organ(s). Skin delivery has shown high potency for immunotherapeutic administration. However, an adequate in vivo model of human skin immunity is still a critical bottleneck. We demonstrated here that the skin of human immune system mice is colonized by human hematopoietic cells, mainly human T cells and that complementation with human antigen-presenting cells at the vaccination site allowed the induction of an immune response.


X-ray and neutron reflectometry investigation of Langmuir-Blodgett films of cellulose ethers.
Langmuir-Blodgett films of a series of cellulose ethers are investigated by X-ray and neutron reflectometry. Two types of samples are considered: simple alkyl ethers of cellulose and derivatives obtained by the alkylation of (2-hydroxypropyl)cellulose (HPC). All of the cellulose ethers form stable monolayers at the air-water interface. Significant differences are, however, found in the surface pressure-area compression isotherms. Ethers prepared from HPC typically exhibit larger limiting molecular areas and higher surface pressures than the corresponding simple cellulose ethers. The ease of monolayer transfer to hydrophobic silicon substrates differs greatly from one type of molecule to another. Successful transfer conditions are found only for ethers that form stable monolayers at sufficiently high surface pressures. Surprisingly, deuterated HPC ethers, prepared for neutron reflectivity measurements, exhibit monolayer properties significantly different from those of their hydrogenated analogues. Although essentially identical limiting molecular areas are found, the surface pressure corresponding to a characteristic plateau transition in the compression isotherm is found to decrease by about 8-10 mN m(-1) upon side chain deuteration. X-ray reflectivity results show a linear increase of film thickness with the number of deposited layers, indicating a regular and reproducible transfer. Observed average layer spacings are, however, significantly smaller than the calculated length of fully extended side chains. Neutron reflectivity curves recorded for composite LB films composed of both deuterated and hydrogenated polymers exhibit regular Keissig fringes, but no Bragg peak. This result indicates that these LB films do not possess an internal periodic structure and the initial layer-by-layer organization is lost by large interlayer diffusion.


Patterns of parasitic infections in faecal samples from stray cat populations in Qatar.
The parasite fauna of stray cat populations, comprising mainly helminth parasites, is described for the first time from the arid environment of the Qatar peninsula. During the winter and summer months of 2005, 824 faecal samples were examined from six sites in Qatar. Up to seven species of parasites were identified, six of which were nematodes - Strongyloides stercoralis as the most prevalent (18.4%), followed by Aelurostrongylus abstrusus (7.5%), Toxocara cati (6.1%), Ancylostoma tubaeforme (5.9%) and Physaloptera sp. (4.8%) and Toxascaris leonina (0.7%) - and one sporozoan species, Isospora felis (0.5%). Unidentified cestode eggs were also recovered from 10.7% of samples examined. The parasite species were found to be highly overdispersed in faecal samples from all sites, whereas the prevalence and intensity of infections were influenced by site and season. Infection levels tended to be higher during the winter season, especially in the case of A. abstrusus and A. tubaeforme, when conditions of temperature and humidity were more favourable for the development of egg and/or larval stages of parasites compared with the extremely hot and dry summer months. The results are discussed in relation to the distribution of the cat population in the vicinity of Doha and its outskirts and the potential threat of parasite transmission to human communities in Qatar.


Use of selective-serotonin reuptake inhibitors and platelet aggregation inhibitors among individuals with co-occurring atherosclerotic cardiovascular disease and depression or anxiety.
Medications commonly used to treat heart disease, anxiety, and depression can interact resulting in an increased risk of bleeding, warranting a cautious approach in medical decision making. This retrospective, descriptive study examined the prevalence and the factors associated with the use of both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor among individuals with co-occurring atherosclerotic cardiovascular disease and anxiety or depression. Respondents aged 22 years and older, alive throughout the study period, and diagnosed with co-occurring atherosclerotic cardiovascular disease and anxiety or depression (n = 1507) in years 2007 through 2013 of the Medical Expenditures Panel Survey were included. The use of treatment was grouped as follows: selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Overall, 16.5% used both selective-serotonin reuptake inhibitor and platelet aggregation inhibitor, 61.2% used selective-serotonin reuptake inhibitor or platelet aggregation inhibitor, and 22.3% used neither selective-serotonin reuptake inhibitor nor platelet aggregation inhibitor. Respondents aged over 65 years (adjusted odds ratio = 1.93 (95% confidence interval = 1.08-3.45)) and having a diagnosis of diabetes (adjusted odds ratio = 1.63 (95% confidence interval = 1.15-2.31)) and hypertension (adjusted odds ratio = 1.84 (95% confidence interval = 1.04-3.27)) were more likely to be prescribed the combination. The drug interaction was prevalent in patients who are already at higher risk of health disparities and worse outcomes thus requiring vigilant evaluation.


Inhibitory effect of interferon on DNA and RNA synthesis in murine spleen cells stimulated by lectins.
Spleen cells from mice inoculated with partially purified preparations of interferon (Sp. Act. 1 X 10(7) i.u./mg protein, 0.2 ml i. v./mouse) were stimulated in vitro with phytohemagglutinin, concanavalin A or lipopolysaccharide. After 2 days of stimulation, the incorporation of 3H-thymidine into TCA-insoluble radioactivity was inhibited 50-90% when compared with cells from animals inoculated with mock interferon. Maximal inhibition, with optimal doses of lectins was obtained when interferon was;inoculated 18 hours before. This effect of interferon on DNA synthesis was preceeded by inhibition of the incorporation of 3H-uridine into TCA-insoluble material. When cells were pretreated in vitro with interferon for 24 hours and subsequently stimulated with PHA, RNA synthesis was inhibited by 30-40%, whatever was the dose of the mitogen. The synthesis of 4S tRNA, 18S and 28S ribosomal RNAs were inhibited to the same degree by interferon. The incorporation of methyl groups into cytoplasmic sRNA was unaltered.


Microscopy Based Methods for the Assessment of Epithelial Cell Migration During In Vitro Wound Healing.
Cell migration is a mandatory aspect for wound healing. Creating artificial wounds on research animal models often results in costly and complicated experimental procedures, while potentially lacking in precision. In vitro culture of epithelial cell lines provides a suitable platform for researching the cell migratory behavior in wound healing and the impact of treatments on these cells. The physiology of epithelial cells is often studied in non-confluent conditions; however, this approach may not resemble natural wound healing conditions. Disrupting the epithelium integrity by mechanical means generates a realistic model, but may impede the application of molecular techniques. Consequently, microscopy based techniques are optimal for studying epithelial cell migration in vitro. Here we detail two specific methods, the artificial wound scratch assay and the artificial migration front assay, that can obtain quantitative and qualitative data, respectively, on the migratory performance of epithelial cells.


A new technique for management of intercavernous sinus bleeding with titanium clips in transsphenoidal surgery.
Venous bleeding induced by intercavernous sinus injury during sellar dural opening is a challenging intraoperative complication and is difficult to treat in transsphenoidal surgery. To date, few studies concerning the management of intercavernous sinus bleeding have been reported. Our aim was to assess the clinical outcomes of a new hemostasis technique utilizing nonpenetrating titanium clips for management of intercavernous sinus bleeding. From January 2007 to July 2008, 242 pituitary tumors were operated using a transnasal transsphenoidal approach. A new technique involving a specially devised clip applier and titanium clips was used to control venous bleeding in 13 (5.4%) patients who exhibited a prominent intercavernous sinus. All patients were evaluated clinically and radiologically at 9 to 24 months, and postoperative magnetic resonance imaging (MRI) was performed at 3 to 18 months. No operation was interrupted or aborted due to ineffective bleeding control, and there was no delayed bleeding noted as a complication. No complications related to the use of the device occurred. Imaging studies revealed no evidence of significant clip artifact. Our surgical experience has revealed that this new hemostasis technique can be a safe, rapid and effective method for control of intercavernous sinus bleeding during sellar dural opening in transsphenoidal surgery. However, a further prospective study to evaluate this method more fully is planned.


Stepping back to advance: Why IGD needs an intensified debate instead of a consensus.
Based on their analysis of Internet gaming disorder (IGD) criteria, Kuss, Griffiths, and Pontes (2017) come to the conclusion that the current situation can be described as "chaos and confusion." Their assessment is not an exaggeration. It can be argued that there are even more issues, on logical/definitional and political/social levels: (a) the IGD diagnosis is lacking a well-defined object, (b) the cause and effect cannot be differentiated outside lab conditions, (c) the social and political effects of declaring a social behavior as a disease are worrying, and (d) a rushed diagnosis may construct an addiction with potentially harmful effects on (formerly) healthy populations. Instead of closing the debate by declaring a consensus and codifying IGD in the DSM, an undogmatic, intensified, and broader discussion is needed.


Performance of Large Language Models (ChatGPT, Bing Search, and Google Bard) in Solving Case Vignettes in Physiology.
Background Large language models (LLMs) have emerged as powerful tools capable of processing and generating human-like text. These LLMs, such as ChatGPT (OpenAI Incorporated, Mission District, San Francisco, United States), Google Bard (Alphabet Inc., CA, US), and Microsoft Bing (Microsoft Corporation, WA, US), have been applied across various domains, demonstrating their potential to assist in solving complex tasks and improving information accessibility. However, their application in solving case vignettes in physiology has not been explored. This study aimed to assess the performance of three LLMs, namely, ChatGPT (3.5; free research version), Google Bard (Experiment), and Microsoft Bing (precise), in answering cases vignettes in Physiology. Methods This cross-sectional study was conducted in July 2023. A total of 77 case vignettes in physiology were prepared by two physiologists and were validated by two other content experts. These cases were presented to each LLM, and their responses were collected. Two physiologists independently rated the answers provided by the LLMs based on their accuracy. The ratings were measured on a scale from 0 to 4 according to the structure of the observed learning outcome (pre-structural = 0, uni-structural = 1, multi-structural = 2, relational = 3, extended-abstract). The scores among the LLMs were compared by Friedman's test and inter-observer agreement was checked by the intraclass correlation coefficient (ICC). Results The overall scores for ChatGPT, Bing, and Bard in the study, with a total of 77 cases, were found to be 3.19±0.3, 2.15±0.6, and 2.91±0.5, respectively, p<0.0001. Hence, ChatGPT 3.5 (free version) obtained the highest score, Bing (Precise) had the lowest score, and Bard (Experiment) fell in between the two in terms of performance. The average ICC values for ChatGPT, Bing, and Bard were 0.858 (95% CI: 0.777 to 0.91, p<0.0001), 0.975 (95% CI: 0.961 to 0.984, p<0.0001), and 0.964 (95% CI: 0.944 to 0.977, p<0.0001), respectively. Conclusion ChatGPT outperformed Bard and Bing in answering case vignettes in physiology. Hence, students and teachers may think about choosing LLMs for their educational purposes accordingly for case-based learning in physiology. Further exploration of their capabilities is needed for adopting those in medical education and support for clinical decision-making.


Juvenile Correctional Officer Beliefs About Trauma and Mental Illness: Perceptions of Training and Youth Behaviors.
Youth with a mental illness are incarcerated at much higher rates than youth without a psychological diagnosis. Correctional officers serve as a source of daily interaction for these youth and are required to manage juvenile mental health symptoms with minimal training. When staff do not fully understand mental health needs or hold stigmatic perceptions, youth may experience negative consequences. Being aware of officer perceptions of juvenile mental health issues has the potential to improve monitoring and treatment of youth at correctional facilities. This study took place at a Midwestern juvenile correctional facility-the only one in the state. Officer attitudes surrounding mental health, mental health training, and treatment needs were assessed among a sample of juvenile correctional officers employed at the facility. Findings suggest overall positive perceptions of juvenile mental health issues, but suggest the need for increased mental health training for juvenile correctional officers.