Ventilation inhomogeneity during controlled ventilation. Which index should be used?
Six indexes for diagnosing uneven ventilation by tracer gas washout were studied. The indexes were lung clearance index, mixing ratio, Becklake index, multiple-breath alveolar mixing inefficiency, moment ratio, and pulmonary clearance delay, all of which increase with impaired pulmonary gas mixing. In model lung tests, indexes that compared the actual washout curve with a calculated ideal curve (mixing ratio, multiple-breath alveolar mixing inefficiency, and pulmonary clearance delay) were unaffected by changes in tidal volume and series dead space, whereas the others varied markedly. In both spontaneously breathing and mechanically ventilated patients all indexes showed a significant difference between smokers and nonsmokers (P less than 0.002), but the indexes were somewhat different in their assessment of different ventilatory patterns. However, the mean value for all indexes, with the exception of mixing ratio, was smallest with a fast insufflation followed by an end-inspiratory pause. Any of the indexes may be useful if its limitations are recognized, but mixing ratio, multiple-breath alveolar mixing inefficiency, and pulmonary clearance delay seem preferable, because they are not affected by changes in tidal volume and dead space fraction.


[Yamatogawa scandal denounces psychiatric treatment system of Japan].
OSAKA Center for Mental Health and Human Rights, established in 1985, has been taking action on the Yamatogawa Hospital Affair. This hospital had developed many scandals for a long time. For example, the inpatients were murdered through the violence by the hospital staffs in 1969, 1979 and 1993. Despite the repeated accusations, this hospital had been allowed to operate until Oct. 1997, when Osaka Prefecture Governor ordered the hospital to stop its operation. Throughout the entire course of this Affair, the Psychiatric Review Board of Osaka Prefecture (regulated and expected to protect the patient's rights by the Mental Health Law and its amendment, the Mental Health and Welfare Law) did not function. The prohibition articles of the Law about restriction on actions, such as correspondence and interview, were not effective and had been neglected. The responsible department of the Prefecture Government had not started the valid investigation into the hospital. We demand the valid measures to protect the human rights of psychiatric patients. The author proposed the independence of the Psychiatric Review Board from the Prefecture Government, the start of the ombudsman system and so on. "Principles" by the UN (1991) should be cleared.


Leishmania braziliensis exosomes activate human macrophages to produce proinflammatory mediators.
Exosomes, organelles measuring 30-200nm, are secreted by various cell types. Leishmania exosomes consist of many proteins, including heat shock proteins, annexins, Glycoprotein 63, proteins exerting signaling activity and those containing mRNA and miRNA. Studies have demonstrated that Leishmania donovani exosomes downregulate IFN-γ and inhibit the expression of microbicidal molecules, such as TNF and nitric oxide, thus creating a microenvironment favoring parasite proliferation. Despite lacking immunological memory, data in the literature suggest that, following initial stimulation, mononuclear phagocytes may become "trained" to respond more effectively to subsequent stimuli. Here we characterized the effects of macrophage sensitization using L. braziliensis exosomes prior to infection by the same pathogen. Human macrophages were stimulated with L. braziliensis exosomes and then infected with L. braziliensis. Higher levels of IL-1β and IL-6 were detected in cultures sensitized prior to infection compared to unstimulated infected cells. Moreover, stimulation with L. braziliensis exosomes induced macrophage production of IL-1β, IL-6, IL-10 and TNF. Inhibition of exosome secretion by L. braziliensis prior to macrophage infection reduced cytokine production and produced lower infection rates than untreated infected cells. Exosome stimulation also induced the consumption/regulation of NLRP3 inflammasome components in macrophages, while the blockade of NLRP3 resulted in lower levels of IL-6 and IL-1β. Our results suggest that L. braziliensis exosomes stimulate macrophages, leading to an exacerbated inflammatory state that may be NLRP3-dependent.


A redox-controlled electrolyte for plasmonic enhanced dye-sensitized solar cells.
Plasmonic enhanced dye-sensitized solar cells (DSSCs) with metallic nanostructures suffer from corrosion problems, especially with the presence of the iodine/triiodide redox couple in the electrolyte. Herein, we introduce an alternative approach by compensating the corrosion with a modified liquid electrolyte. In contrast to the existing method of surface preservation for plasmonic nanostructures, the redox-controlled electrolyte (RCE) contains iodoaurate intermediates, i.e. gold(i) diiodide (AuI2-) and gold(iii) tetraiodide (AuI4-) with optimal concentrations, such that these intermediates are readily reduced to gold nanoparticles during the operation of DSSCs. As corrosion and redeposition of gold occur simultaneously, it effectively provides corrosion compensation to the plasmonic gold nanostructures embedded in the photoanode. Cycling tests of the specific amount of gold contents in the RCE of DSSCs support the fact that the dissolution and deposition of gold are reversible and repeatable. This gold deposition on the TiO2 photoanode results in forming a Schottky barrier (SB) at the metal-semiconductor interface and effectively inhibits the recombination of electron-hole pairs. Therefore, the RCE increases the short-circuit current, amplifies the open-circuit voltage, and reduces the impedance of the TiO2/dye interface. The power conversion efficiency of DSSCs was improved by 57% after incorporating the RCE.


[Hearing aid fitting in children with difficulties processing auditory information-evaluation of parents' satisfaction].
Some children suffer from difficulties processing auditory information despite normal cochlear function. Here we raised the question if hearing aid (HA) fitting might be beneficial for such children. 32 children with auditory information processing deficits were fitted with HA. Three months after fitting parents were asked about individual benefits for hearing behavior using a questionnaire. Parents' rating indicated a significant improvement of auditory information processing after HA fitting. A high internal consistence of subscales except for loudness perception was found. According to the data presented it seems reasonable to assume that hearing aids may ameliorate adverse affects of auditory processing deficits. Further studies supporting these findings and possibly including an audiometric proof are warranted.


Advances in sex disparities for cancer immunotherapy: unveiling the dilemma of Yin and Yang.
A wide sex disparity has been demonstrated in cancer incidence, tumor aggressiveness, prognosis, and treatment response of different types of cancer. The sex specificity of cancer appears to be a relevant issue in managing the disease, and studies investigating the role of sex and gender are becoming extremely urgent. Immunotherapy plays a leading role in cancer treatment, offering a new perspective on advanced malignancies. Gender has not been considered in standard cancer treatment, suggesting increasing the recognition of sex differences in cancer research and clinical management. This paper provides an overview of sex and gender disparities in cancer immunotherapy efficacy, anti-cancer immune response, predictive biomarkers, and so on. We focus on the molecular differences between male and female patients across a broad range of cancer types to arouse the attention and practice of clinicians and researchers in a sex perspective of new cancer treatment strategies.


Dereplication of terpenes and phenolic compounds from Inga edulis extracts using HPLC-SPE-TT, RP-HPLC-PDA and NMR spectroscopy.
Inga edulis is traditionally used as anti-inflammatory and antidiarrheal and has been investigated as potential sources of biologically active natural products. In this study, dereplication strategy using HPLC-SPE-TT, RP-HPLC-PDA and NMR spectroscopy was employed, and this resulted in the identification of sixteen compounds from the leaves extract of I. edulis, including four triterpenes (lupeol, α-amirin, olean-18-ene acid and frideline), three flavonoids, eight phenolic acids, an anthocyanin derived from delphinidin-3-glycoside and a mixture of five acylated anthocyanins. The chemical identification was performed based on NMR data, chemosystematics aspects, UV spectra and by comparison with the retention time and UV spectra of authentic standards. The metabolic profile of the species indicated the presence of phenolic compounds as major constituents justifying its strong antioxidant potential performed in β-carotene test. The techniques used have shown effective strategies for the early detection of active natural products from plant extracts, as these approaches are still crucially absent.[Formula: see text].


The potentials and challenges of using fermentation to improve the sensory quality of plant-based meat analogs.
Despite the advancements made in improving the quality of plant-based meat substitutes, more work needs to be done to match the texture, appearance, and flavor of real meat. This review aims to cover the sensory quality constraints of plant-based meat analogs and provides fermentation as a sustainable approach to push these boundaries. Plant-based meat analogs have been observed to have weak and soft textural quality, poor mouth feel, an unstable color, and unpleasant and beany flavors in some cases, necessitating the search for efficient novel technologies. A wide range of microorganisms, including bacteria such as Lactobacillus acidophilus and Lactiplantibacillus plantarum, as well as fungi like Fusarium venenatum and Neurospora intermedia, have improved the product texture to mimic fibrous meat structures. Additionally, the chewiness and hardness of the resulting meat analogs have been further improved through the use of Bacillus subtilis. However, excessive fermentation may result in a decrease in the final product's firmness and produce a slimy texture. Similarly, several microbial metabolites can mimic the color and flavor of meat, with some concerns. It appears that fermentation is a promising approach to modulating the sensory profiles of plant-derived meat ingredients without adverse consequences. In addition, the technology of starter cultures can be optimized and introduced as a new strategy to enhance the organoleptic properties of plant-based meat while still meeting the needs of an expanding and sustainable economy.


Cs4PbX6 (X = Cl, Br, I) Nanocrystals: Preparation, Water-Triggered Transformation Behavior, and Anti-Counterfeiting Application.
As a promising material, Cs4PbX6 (X = Cl, Br, I) nanocrystals (NCs) have attracted much attention. However, their luminescent property is still under debate. In this work, we first systematically studied the colloidal preparation of Cs4PbX6 NCs. It is found that the critical parameter for the formation of Cs4PbX6 NCs is the ratio between Cs and Pb. Pure Cs4PbX6 NCs are nonluminescent. The luminescence property of previous reported Cs4PbX6 NCs may come from the impurity of luminescent CsPbX3 NCs. No coexistence of both Cs4PbX6 and CsPbX3 phase has been found in one single nanoparticle. The water-triggered transformation from nonluminescent Cs4PbX6 NCs to luminescent CsPbX3 NCs has been quantitatively studied. The potential application of Cs4PbX6 NCs in humidity sensor and anticounterfeiting have been demonstrated. This work is important because it not only confirmed the nonluminescent nature of Cs4PbX6 NCs but also demonstrated the potential application of such NCs.


The effect of 17% EDTA and QMiX ultrasonic activation on smear layer removal and sealer penetration: ex vivo study.
This study aimed to compare the effect of conventional irrigation (CI) and passive ultrasonic irrigation (PUI) with 17% EDTA and QMiX on the maximum depth and percentage of sealer penetration into the dentinal tubules by confocal laser scanning microscopy (CLSM) and to describe the cleaning of root canal walls by scanning electron microscopy (SEM). Eighty single-rooted human mandibular premolars were instrumented and randomly assigned to four groups (n = 20): EDTA + CI, QMiX + CI, EDTA + PUI, and QMiX + PUI. Ten samples from each group were examined by SEM (2,000×) and the remaining 40 roots were filled with a single gutta-percha cone and AH Plus sealer mixed with 0.1% rhodamine B for analysis by CLSM (10×). Images were assessed at distances of 2 mm (apical), 5 mm (middle), and 8 mm (coronal) from the apex with the Leica Application Suite V4.10 software. The EDTA + PUI and QMiX + PUI protocols presented higher rates of debris/smear layer removal in the apical and middle thirds. The PUI was superior to CI in the maximum depth of sealer penetration at the middle third. The QMiX + PUI group had a higher percentage of sealer penetration at the apical third. The PUI and QMiX protocol improved debris/smear layer removal and tubular dentin sealer penetration.


The sigma-1 receptor as a regulator of dopamine neurotransmission: A potential therapeutic target for methamphetamine addiction.
Methamphetamine (METH) abuse is a major public health issue around the world, yet there are currently no effective pharmacotherapies for the treatment of METH addiction. METH is a potent psychostimulant that increases extracellular dopamine levels by targeting the dopamine transporter (DAT) and alters neuronal activity in the reward centers of the brain. One promising therapeutic target for the treatment of METH addiction is the sigma-1 receptor (σ1R). The σ1R is an endoplasmic reticulum-localized chaperone protein that is activated by cellular stress, and, unique to this chaperone, its function can also be induced or inhibited by different ligands. Upon activation of this unique "chaperone receptor", the σ1R regulates a variety of cellular functions and possesses neuroprotective activity in the brain. Interestingly, a variety of σ1R ligands modulate dopamine neurotransmission and reduce the behavioral effects of METH in animal models of addictive behavior, suggesting that the σ1R may be a viable therapeutic target for the treatment of METH addiction. In this review, we provide background on METH and the σ1R as well as a literature review regarding the role of σ1Rs in modulating both dopamine neurotransmission and the effects of METH. We aim to highlight the complexities of σ1R pharmacology and function as well as the therapeutic potential of the σ1R as a target for the treatment of METH addiction.


Synergistic antiproliferative effects of methotrexate-loaded smart silica nanocomposites in MDA-MB-231 breast cancer cells.
In this study, the ability of methotrexate (MTX)-loaded stimuli-responsive novel silica nanocomposites (MSNs) (with mean diameter of ± 60 nm) in the induction of apoptosis, and change in the Bax/Bcl-2 mRNA levels, were investigated. MTT assay and RT -PCR analysis were performed on MDA-MB-231 breast cancer cells, to evaluate their anti-proliferative, apoptotic and anti-apoptotic effects. MTX-loaded MSNs caused marked decrease in the percentage of viable cells, with a significant down-regulation in the level of expression of the anti-apoptotic gene (Bcl-2), and up-regulation in the apoptotic gene (Bax). MTX-loaded MSNs increased the efficacy of the chemotherapeutic agents in the inhibition of cell proliferation and induction of apoptosis.


Juxta-clavicular beaded lines in a kidney transplant patient receiving immunosuppressants.
Juxta-clavicular beaded lines (JCBL) are unique malformations of sebaceous glands or a variant of sebaceous hyperplasia with characteristic clinical features (1, 2). We describe a patient with JCBL, who received immunosuppressants following kidney transplantation. To our knowledge, our patient is the first case of JCBL in a kidney transplant recipient.


Tissue iodoprotein formation during the peripheral metabolism of the thyroid hormones.
The formation of tissue iodoproteins during the peripheral metabolism of the thyroid hormones was examined by determining the concentration of nonethanol-extractable (125)I (NE(125)I) in various tissues after the intravenous injection of 3,5,3'-triiodo-L-thyronine (T3-(125)I) and L-thyroxine-(125)I (T4-(125)I) in groups of rats with iodide-blocked thyroid glands. 3 days after T3-(125)I and 7 days after T4-(125)I injection the concentration of NE(125)I in the liver and kidney was 5-10 times greater than in plasma. Smaller but nonetheless significant concentrations of NE(125)I were demonstrated in skeletal and cardiac muscle. Hepatic subcellular fractionation studies revealed that the major portion of the liver NE(125)I was in the microsomal fraction. Lower concentrations of NE(125)I were present in the nuclear, mitochondrial, and soluble fractions. When similar studies were performed in groups of rats pretreated with phenobarbital, an increase in the metabolic clearance of T3-(125)I (30%) and T4-(125)I (100%) was observed along with a highly significant increase in the NE(125)I concentration of the liver and plasma. The increase in hepatic NE(125)I in these studies was primarily due to the microsomal component. Incubation of hepatic microsomes with T3-(125)I and T4-(125)I showed that NEI formation as well as deiodination appeared to obey simple Michaelis-Menten kinetics. Moreover, the maximal rate of both deiodination and NEI formation was increased when microsomes harvested from phenobarbital-treated rats were employed. These studies indicate that thyroid hormone metabolism results in the formation of structural and soluble tissue iodoproteins in addition to circulating iodoproteins. The rate of formation of these moieties in the liver and plasma appears to be related to the rate of hormone metabolism.


Pediatric systemic lupus erythematosus with C1q deficiency.
Hereditary deficiency of each component of the classical pathway is associated with increased susceptibility to lupus erythematosus (LE). Both the severity of the disease and the strength of this association are greatest for homozygous C1q deficiency, which is extremely rare. In fact, more than 90% of all individuals with deficiency of this component have LE. We report a 3-year-old female infant with history of discoid LE treated with topical corticosteroids for 1 year. She was referred to pediatric department for an exacerbation and extension of cutaneous lesions toward front-arm, hands, legs and feet, a glomerulonephritis, and thrombopenia. Immunologic tests revealed a positive speckled antinuclear antibody at 1/1600 with positive anti-Sm, anti-SSA, and anti-RNP antibodies. Test for anti-DNA was negative. These findings were compatible with a transition to a systemic form of lupus. Systemic corticosteroid treatment was started; however, the patient died by a severe digestive hemorrhage. Hemolytic complement activity (CH50) was undetectable in serum despite normal levels of C3 and C4 suggesting a deficiency of an early component of the complement cascade. Measurement of hemolytic assay for C1 functional activity was less than 1%. C1q deficiency was confirmed by a double immunodiffusion and ELISA using sheep polyclonal anti-C1q antibodies. C1q deficiency is a rare genetic disorder. Thirty-eight of the 41 patients reported to date have developed systemic LE. C1q deficiency may cause systemic LE via a critical role of this component in the physiological clearance of apoptotic cells.


Rotational Stability of a New Posterior Chamber Toric Phakic Intraocular Lens.
To evaluate the refractive results and rotational stability of Eyecryl toric phakic intraocular lens (pIOL). In this retrospective single-surgeon case series, manifest refraction, visual acuities, endothelial cell density (ECD), and pIOL rotation were evaluated over 6 months. 43 eyes from 23 patients were included. At 6 months, the SE was within ±0.50 D of emmetropia in 30 (70%) eyes and within ±1.00 D of emmetropia in 39 (91%) eyes. The efficacy and safety indices were 1.25 ± 0.38 and 1.41 ± 0.34, respectively. Mean ECD was 2719 ± 296 cells/mm2 at the preoperative visit and 2779.42 ± 422 cells/mm2 at the 6-month visit (p > 0.05). The mean value of absolute axis orientation error was 4.95 ± 5.28°. Mean absolute change in axis orientation between visits was less than 3° for all visit intervals. Ninety percent or more of lenses were found to rotate 5° or less between all visit intervals. None of the patients experienced a vision-threatening complication, and no patient required secondary IOL repositioning. The pIOL appears to effectively reduce subjective manifest astigmatism and provide good visual acuity. Its position was found to be stable throughout the follow-up.


Giant concha bullosa presented as left nasal mass: a case report and literature review.
Concha bullosa (CB) is not considered to be a disease, but rather a variation of the paranasal sinus. A CB is defined as the presence of an air cell within the turbinate (pneumatization). The main function of CB is to maintain upper respiratory humidity, regulate thermoregulation, and regulate airflow and filtration. It is common for CB to occur in the middle turbinate, while superior and inferior locations appear to be rare. The patient in this case report was presented mainly with nasal obstruction. During examination, a large mass was found in the left nasal cavity, causing a deviated nasal septum to the right. For this patient, surgery was the last resort. Either perioperative or postoperative complications were observed, and the quality of life of patients improved after surgery.


Strategic sequence planning and prospective memory impairments in frontally lesioned head trauma patients performing activities of daily living.
The aim of this research was to study strategic sequence planning and prospective memory in activities of daily living (ADL) in 10 patients with frontal lobe lesions after a mild to moderate closed head injury (CHI). The lesions were documented radiologically. The CHI patients were compared to 12 normal controls with a neuropsychological test battery and a realistic simulation of complex multitask ADL (planning and preparing a meal). Though the CHI patients were significantly slow on one test and subject to interference on an attention test, they manifested no basic executive or memory deficit on the paper-pencil tests. However, the CHI patients manifested marked anomalies in the organization of behavior in the meal preparation task. While small sequences of actions were easily produced, large action sets could not be correctly executed. An outstanding difficulty in strategic planning and prospective memory, particularly time-based more than event-based, appears to be an important underpinning of the impairment of ADL observed in the CHI patients with frontal lobe lesions.


Screening for Antimicrobial Activity of Wood Rotting Higher Basidiomycetes Mushrooms from Uruguay against Phytopathogens.
In this work, the antimicrobial activity of extracts of wood rotting higher Basidiomycetes mushrooms isolated from Eucalyptus plantations in Uruguay was studied using bacterial and fungal phytopathogens as targets. Fifty-one extracts from mycelia and growth broth were prepared from higher Basidiomycetes mushrooms, from which eight extracts (from Ganoderma resinaceum, Laetiporus sulphureus, Dictyopanus pusillus, and Bjerkandera adusta) showed antimicrobial activity against Xanthomonas vesicatoria, Aspergillus oryzae, Penicillium expansum, Botrytis cinerea, and Rhizopus stolonifer as assayed in the qualitative test. The minimum inhibitory concentration (MIC) for those fungal extracts was determined and the results showed that L. sulphureus deserved further study, with low MIC values against X. vesicatoria. The antimicrobial activity of L. sulphureus culture broth extracts grown under different culture conditions was evaluated against X. vesicatoria. From the results of these assays, larger-scale cultures for the production of the compound(s) with antimicrobial activity should be performed using malt extract broth, at pH 5, at 20°C and static culture conditions.


Improving the safety and effectiveness of parenteral nutrition: results of a quality improvement collaboration.
Parenteral nutrition (PN) is a high-risk nutrition support modality. This article describes the approach taken by 1 hospital to improve safety and quality of this therapy as well as the challenges and obstacles to success. Process improvement strategies included revisions to the PN order form, education of clinicians (including physicians), increased collaboration between pharmacists and registered dietitians, and initiation of PN rounds during which PN patients were reviewed by the rounding team twice weekly. These strategies were spearheaded by clinicians with advanced certifications in nutrition support. These process changes positively impacted quality and costs. Comparison of baseline and follow-up data showed improvement in compliance to mandatory safe practice standards, percentage of patients with appropriate indication for PN, adequote glycemic management, number of patients receiving PN within 10% of calorie needs, and appropriate laboratory monitoring. In addition to quality improvement, substantial cost savings were realized through decreased inappropriate PN use and timely transition to oral or enteral feeding. The average number of patients receiving PN decreased from approximately 15 to less than 5 per day. Overall, this translated into a $5.3 million decrease in PN charges. Actual pharmacy expenses decreased by $107,000. This quality improvement project demonstrated that implementing practice guidelines published by the American Society for Parental and Enteral Nutrition can result in quality improvement and cost savings. Clinicians with advanced certifications in nutrition support were pivotal to the success of the project.


Comparison of two algorithms and their associated charges when evaluating adrenal masses in patients with malignancies.
This study was performed to compare two proposed algorithms used when evaluating an adrenal mass discovered during staging evaluation of a patient with a known malignancy. Such evaluation was meant to lead to determination of the relative charges associated with each algorithm. Fifty-four patients with known malignancies who required evaluation of an adrenal mass underwent both chemical shift imaging (CSI) and CT-guided for CSI. The hospital charges incurred for each procedure and any associated complications were normalized using national relative-value scale charges and conversion factors. A decision analysis was performed to compare the relative charges that would have been incurred if adrenal MR imaging had been performed in all patients, followed by CT-guided biopsy only in those patients with MR findings not diagnostic of adrenocortical adenoma, and the relative charges incurred if only CT-guided adrenal biopsy had been performed in every patient. Twenty-three (43%) of 54 adrenal masses were shown to be metastases by CT-guided biopsy. The sensitivity and specificity of CSI for the diagnosis of adrenocortical adenoma were 94% and 100%, respectively. The charges incurred by performing MR imaging as the initial examination with subsequent CT-guided biopsy only in those patients with CSI findings not diagnostic of adenoma would have been similar to those incurred by first performing CT-guided adrenal biopsy in every patient. CSI is an accurate, noninvasive technique for evaluating adrenal masses in patients with cancer. If CT-guided biopsy is used only when CSI is not diagnostic of adrenocortical adenoma, the associated charges would be virtually the same as when CT-guided biopsy is performed as the first test in every patient. Moreover, biopsies could have been avoided in 54% of these patients.


Coalescence of endothelial cells in the traumatized cornea. III. Correlation between specular and scanning electron microscopy.
Sequential specular microscopy has shown that coalescence of endothelial cells occurs after thawing in cryopreserved rabbit corneas. Scanning electron microscopy of corneas studied in vitro by specular microscopy showed the same large, fused endothelial cells. As observed in the electron micrographs, these cells showed no evidence of the cell borders that had disappeared during the specular microscopic examination. These data support the reliability of our specular microscopic observations and provide additional evidence for the occurrence of fusion or coalescence of corneal endothelial cells.


Urban-Rural Differences in Clinical Characteristics of Prostate Cancer at Initial Diagnosis: A Single-Center Observational Study in Anhui Province, China.
People residing in rural areas have higher prostate cancer (PCa) mortality to incidence ratio (M/I) and worse prognosis than those in urban areas of China. Clinical characteristics at initial diagnosis are significantly associated with biochemical recurrence, overall survival, and PCa disease-free survival. This study aimed at investigating the clinical characteristics at initial diagnosis of urban and rural PCa patients and to establish a logistic regression model for identifying independent predictors for high-grade PCa. Clinical characteristics for PCa patients were collected from the largest prostate biopsy center in Anhui province, China, from December 2015 to March 2019. First, urban-rural disparities in clinical characteristics were evaluated at initial diagnosis. Second, based on pathological findings, we classified all participants into the benign+ low/intermediate-grade PCa or high-grade PCa groups. Univariate and multivariate logistic regression analyses were performed to identify independent factors for predicting high-grade PCa, while a nomogram for predicting high-grade PCa was generated based on all independent factors. The model was evaluated using area under receiver-operating characteristic (ROC) curve as well as calibration curve analyses and compared to a model without the place of residence factor of individuals. Statistically significant differences were observed between urban and rural PCa patients with regard to tPSA, PSA density (PSAD), and Gleason score (GS) (p < 0.05). Logistic regression analysis revealed that tPSA [OR = 1.060, 95% confidence interval (CI): 1.024, 1.098], PSAD (OR = 14.678, 95%CI: 4.137, 52.071), place of residence of individuals (OR = 5.900, 95%CI: 1.068, 32.601), and prostate imaging reporting and data system version 2 (PI-RADS v2) (OR = 4.360, 95%CI: 1.953, 9.733) were independent predictive factors for high-grade PCa. The area under the curve (AUC) of the nomogram was greater than that of the model without the place of residence of individuals. The calibration curve of the nomogram indicated that the prediction curve was basically fitted to the standard curve, suggesting that the prediction model had a better calibration ability. Compared to urban PCa patients, rural PCa patients presented elevated tPSA, PSAD levels, and higher pathological grades. The place of residence of the individuals was an independent predictor for high-grade PCa in Anhui Province, China. Therefore, appropriate strategies, such as narrowing urban-rural gaps in access to health care and increasing awareness on the importance of early detection should be implemented to reduce PCa mortality rates.


HIF-1 as a target for drug development.
Sensing and responding to fluxes in oxygen tension is perhaps the single most important variable in physiology, and animal tissues have developed a number of essential mechanisms to cope with the stress of low physiological oxygen levels, or hypoxia. Among these coping mechanisms is the response mediated by the hypoxia-inducible transcription factor, or HIF-1. HIF-1 is an essential component in changing the transcriptional repertoire of tissues as oxygen levels drop, and could prove to be a very important target for drug development, as treatments evolve for diseases, such as cancer, heart disease and stroke, in which hypoxia is a central aspect.


Factor Analysis of the MSVT, NV-MSVT, and RBANS Memory Subtests.
The current investigation sought to define the relationship between established performance validity tests and measures of memory via a factor analytic strategy first published by Heyanka, Thaler, Linck, Pastorek, Miller, Romesser, & Sim (2015). A Factor analytic approach to the validation of the Word Memory Test and Test of Memory Malingering as measures of effort and not memory. Archives of Clinical Neuropsychology, 30, 369-376. The full range of Medical Symptom Validity Test (MSVT) and Non-Verbal Medical Symptom Validity Test (NV-MSVT) subtests were factor analyzed with the memory scales of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) in a sample of 346 service members with a history of concussion. A two-factor solution was extracted with the MSVT and NV-MSVT effort and paired associate subtests loading on one factor and the RBANS subtests loading on a second factor. Results support the conclusion that the effort subtests of the MSVT and NV-MSVT tap a different construct from established memory measures.


1,3-Propane sultone as an extremely potent human carcinogen: description of an exposed cohort in Germany.
1,3-Propane sultone (1,3-PS) is a directly alkylating, genotoxic and carcinogenic substance. In rats, 1,3-PS induces local and systemic tumors at multiple sites, including the mammary gland, intestine, hematopoietic system, kidneys, and the central nervous system (CNS), especially in the form of gliomas. In one particular company, 1,3-PS had been manufactured in limited amounts in the 1950s and 1960s, and for a few purposes until the 1970s. The number of individuals having been in contact with the compound occupationally comprised 55 in total. Data were obtained from this group with an open question of legal compensation regarding an occupational disease. Particular emphasis was placed on malignancies occurring among the occupationally exposed persons. As cerebral gliomas are a major type of tumor induced by 1,3-PS experimentally, the occurrence of two glioblastomas among the previously exposed persons was significant. Three intestinal malignancies were recorded within the cases observed. It is also noteworthy that there was one case of a duodenal carcinoma, which is normally a rare human malignancy. Two hematopoietic/lymphatic malignancies were observed, and there was one case of a renal cell carcinoma. The types of malignancies within a group of only 55 exposed persons are surprisingly consistent with the results from rodent studies. Data clearly indicate that 1,3-PS is carcinogenic in humans. Evidence indicates that 12 cases with various neoplasms were legally compensated within the period of 1985-2010 as an occupational disease, based on the "opening clause" of § 9 (2) SGB VII of legislation in Germany.


IL-10-Producing Infliximab-Specific T Cells Regulate the Antidrug T Cell Response in Exposed Patients.
Infliximab (IFX) is a chimeric mAb that can lead to the appearance of anti-drug Abs. Recent research has identified the presence of circulating IFX-specific T cells in treated patients. The aim of the study was to analyze the functional characteristics of IFX-specific T cells, in particular their capability to produce biologically active regulatory cytokines. Drug-stimulated PBMCs or coculture systems were used to detect memory T cells in treated patients. The cytokines produced by IFX-specific T cells, T cell lines, and T cell clones were evaluated at the mRNA and protein levels. Drug infusion induced an increase in IL-10 serum levels in vivo, whereas other cytokines were unchanged. IL-10 mRNA was higher in IFX-stimulated PBMCs from treated patients compared with untreated patients. When analyzed longitudinally, an early IL-10 mRNA expression was observed. HLA class II-restricted IL-10 production by drug-specific T cells from exposed patients was observed in different experimental settings, such as a coculture system, sorted CD154+ T cells, IFX peptide-stimulated PBMCs, and IFX-specific T cell clones. Finally, IL-10-producing drug-specific T cell clones downregulated the response of autologous effector T cells to IFX. Overall, these findings identify IFX-specific T cells as a source of biologically active IL-10 and suggest interference by IL-10-producing cells in the detection of drug-specific T cells.


Water-assisted growth of uniform 100 mm diameter SWCNT arrays.
We report a simple method for growing high-quality single-walled carbon nanotube (SWCNT) arrays on 100 mm wafers via the addition of water vapor to highly purified gases during the CNT growth step. We show that adding a small amount of water during growth helps to create a uniform catalyst distribution and yields high-quality (Raman G/D of 26 ± 3), high-density (up to 6 × 10(11) cm(-2)) and uniform SWCNT arrays on 100 mm large wafers. We rationalize our finding by suggesting that the addition of water decreases catalyst mobility, preventing its coarsening at higher temperatures. We also report a new mechanism of catalyst inactivation in wafer-scale growth using ultrapurified gas sources by the formation of large, 5 ± 3 μm iron particles. We found such formations to be common for substrates with large temperature gradients, such as for wafers processed in a typical cold-wall chemical vapor deposition reactor.


Patient Outcomes on Day 4 of Intravenous Antibiotic Therapy in Non-Intensive Care Unit Hospitalized Adults With Community-Acquired Bacterial Pneumonia.
Community-acquired bacterial pneumonia (CABP) is a leading cause of morbidity and mortality especially in hospitalized patients. In place of clinical end points traditionally used to evaluate antimicrobial efficacy for its treatment, Food and Drug Administration guidelines now require all registration trials to assess clinical response at day 4. The primary objective of this study was to assess health outcomes (length of stay [LOS] and hospital charges) between responders and nonresponders at this time point. The Premier database was used to identify adult patients from 4 participating hospitals with a principal diagnosis of CABP (International Classification of Diseases, Ninth Revision, Clinical Modification, codes 481, 482.0, 483.8, 484.3, 484.5, 485, 486, or 487.0) hospitalized between July 1, 2010, and June 30, 2011. Only non-intensive care unit patients with hospital stays exceeding 2 days and receiving intravenous antibiotic agents within 24 hours of admission were included. After institutional review board approvals, a retrospective chart review extracted data for patient demographics, clinical efficacy variables at day 4, LOS, and total hospital charges. Data analysis included multivariable gamma regression models to control for patient demographics and clinical differences between responders and nonresponders. A total of 666 patients met study the criteria. Mean (SD) age was 70.7 (17.9) years, and 42.5% were males. Among these patients, 277 (41.6%) achieved clinical response by day 4 of initial antibiotic therapy. The unadjusted mean (SD) LOS was 6.3 (2.8) days for responders and 7.4 (5.6) days for nonresponders (P = 0.0009). Respective unadjusted total hospital charges were $22,827 (SD, $17,724) and $26,403 ($36,882) (P = 0.0031). Adjusted for demographics and clinical factors, nonresponders compared with responders had an increased LOS of 0.9 days (8.4 vs 7.5 days; P = 0.0008), resulting in associated charges of approximately $2500 ($34,139 vs $36,629; P = 0.0768). In this real-world chart study, less than half of hospitalized patients with CABP achieved clinical response at day 4 of initial intravenous antibiotic therapy. The observed clinical response was associated with a significantly shorter hospital stay and trended toward lower total hospital charges. These findings corroborate the Food and Drug Administration guidance for assessing antimicrobial therapy at day 4 because responder is associated with improved health outcomes.


Genome-Wide Identification and Expression Profiles of C-Repeat Binding Factor Transcription Factors in Betula platyphylla under Abiotic Stress.
CBF (C-repeat binding factor) transcription factor subfamily belongs to AP2/ERF (Apetala 2/ethylene-responsive factor) transcription factor family, known for playing a vital role in plant abiotic stress response. Although some CBF transcription factors have been identified in several species, such as Arabidopsis, tobacco, tomato and poplar, research of CBF focus mainly on model plant Arabidopsis and have not been reported in Betula platyphylla yet. In this study, a total of 20 BpCBF subfamily members were identified. The conserved domains, physicochemical properties, exon-intron gene structure and the structure of conserved protein motifs of BpCBFs were analyzed via bioinformatic tools. The collinearity analysis of CBF genes was performed between Betula platyphylla and Arabidopsis thaliana, Betula platyphylla, and Populus trichocarpa. The cis-acting elements in the promoter region of BpCBFs were identified, which were mainly environmental stress-related and hormone-related element components. In this case, the expression patterns of the 20 BpCBFs upon ABA or salt treatment were investigated. Most of these transcription factors were responsive to ABA or salt stress in different plant tissues. The up-regulation trend upon cold treatment of the six cold-responsive genes validated by qRT-PCR was consistent with the result of RNA-seq. BpCBF7 showed transcription activating activity. This study sheds light on the responses of BpCBFs to abiotic stress and provides a reference for further study of CBF transcription factors in woody plants.


[Effect of lead-exposed astrocytes on neuronal synaptic formation].
To investigate the effect of lead-exposed astrocyte conditioned medium (ACM) on the synaptic formation of neurons and to provide reference for the mechanism of lead neurotoxicity. Astrocytes were cultured in the medium containing 50, 100, 200, 400, and 800 µmol/L lead acetate for 72 h. Alamar Blue was used to assess the cell viability of astrocytes, and then ACM was collected. Primarily cultured neurons were divided into six groups: pure culture group, non-glutamic acid (Glu)-induced ACM treatment group, Glu-induced lead-free ACM treatment group, and Glu-induced 50, 100, and 200 µmol/L lead acetate-exposed ACM treatment groups. Neurons were collected after being cultured in ACM for 24, 48, or 72 h. The content of synaptophysin (SYP) in neurons was determined by Western blot. The SYP expression in neurons was measured by immunofluorescence after being cultured in ACMfor 72 h. In all lead-exposed groups, the cell viability of astrocytes declined with increasing concentration of lead (P < 0.05). The Western blot showed that compared with the pure culture group, the non-Glu-induced ACM treatment group and Glu-induced lead- free ACM treatment group had significantly increased content of SYP in neurons (P < 0.01); compared with the non-Glu-induced ACM treatment group, the Glu-induced ACM treatment groups had significantly reduced SYP expression in neurons (P < 0.05); compared with the Glu-induced lead-free ACM treatment group, all lead-exposed ACM treatment groups had the content of SYP in neurons significantly reduced with increasing concentration of lead after 72-h culture (P < 0.01), the 200 µmol/L lead-exposed ACM treatment group had significantly reduced content of SYP in neurons after 48-h culture (P < 0.01), and all lead-exposed ACM treatment groups showed no significant changes in the content of SYP in neurons after 24-h culture. Double-labeling immunofluorescence of SYP showed that all lead-exposed ACM treatment groups had a significant decrease in the number of SYP-fluorescent particles after 72-h culture (P < 0.05). Astrocytes promote synaptic formation of neurons, which may be inhibited during lead exposure.


In vitro assessment of the indirect antioxidant activity of Sulforaphane in redox imbalance vanadium-induced.
Owing to sulforaphane presence, a dietary consumption of Brassicaceae prevents chronic diseases. This hormetic compound induces adaptive stress response at subtoxic doses, while doses that exceed the cellular defence are toxic. In HepG2, Caco-2 and Vero cells, we investigated the sulforaphane (SFN) (5 μM) role in counteracting redox imbalance induced by VOSO4 [V(IV)]. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test showed a dose-dependent viability reduction (r < -0.95; p < 0.01) (range 5-80 μM). At 5 μM, SFN enhancement of mitochondrial activity was confirmed by Δψm (p < 0.05) both in basal condition and in redox-stressed cells. Intracellular ROS, DNA and lysosomal oxidative damages underlined the indirect antioxidant SFN activity, confirmed by the increase of GSH. The SFN empowering effects on mitochondrial function were imputable to the presence of mitochondrial proteins among the Nrf2-responsive phase II proteins. Considering the link between oxidative stress and chronic diseases, a long-term dietary intake of Brassicaceae could be strongly advisable.


Concurrent acetylcholinesterase staining and gamma-aminobutyric acid uptake of cortical neurons in culture.
Gamma-aminobutyric acid (GABA) uptake and acetylcholinesterase (AChE) content were demonstrated concurrently in cortical neurons grown in tissue culture. Positive reactions either for GABA uptake or for AChE content were encountered in pyramidal and stellate, as well as spindle-shaped neurons. Neither reaction was confined to a specific morphological subtype. Nearly half the neurons were negative for either reaction. Most of the remaining neurons were positive only for GABA or only for AChE. However, a subpopulation of neurons showed not only a high AChE content, but also an avid GABA uptake. Thus, four types of neurons could be identified on the basis of these two reactions. The high AChE content in some of the cortical neurons that also showed GABA uptake indicates that there are at least two distinct types of GABAergic neurons.


Hierarchical collective motion of a mixture of active dipolar Janus particles and passive charged colloids in two dimensions.
We use computer simulations to study the behavior of a mixture of large passive charged colloids in a suspension of smaller active dipolar Janus particles. We find that when a single charged colloid is present in solution, it acquires a rotational or translational motion depending on how the active dipoles self-assemble on its surface to form active complexes. The collective behavior of these complexes is quite remarkable, and includes swarming behavior and coherent macroscopic motion. We detail how the variety of different phenomenologies emerging in this system can ultimately be controlled by the strength of the active forces and the relative concentration of the two species.


Large third-order optical nonlinear effects of gold nanoparticles with unusual fluorescence enhancement.
The third-order nonlinear optical properties of two solutions of gold nanoparticles protected by carbazolyldiacetylene derivatives were investigated using the Z-scan technique. Both gold nanoparticle colloid solutions in toluene show unusual fluorescent enhancement and large third-order nonlinear optical properties including nonlinear absorption and refractive effects. When extending the pi-conjugated length of the ligands, the third-order nonlinear properties of composite materials based on gold nanoparticles were enhanced accordingly.


[Allogeneic hematopoietic stem cell transplantation in patients with multiple myeloma].
To analyze the effectiveness of allogeneic hematopoietic stem cell transplantation (allo-HSCT) from a related HLA-identical donor in patients with multiple myeloma (MM). From 2013 to 2018, the study included 8 patients (6 men, 2 women) aged from 27 to 55 years (median 39 years) with MM who underwent allo-HSCT from a related HLA-identical donor (7 patients after auto-HSCT, in 1 case without previous auto-transplantation). All patients required 2 or more lines of induction therapy, while the achieved antitumor effect was unstable. Before allo-HSCT, complete and very good partial remission was determined in isolated cases, in 4 patients the response was regarded as partial remission, stabilization in 1 observation, progression in 1 patient. All patients underwent reduced intensity conditioning (fludarabine 30 mg/m2 6 days + busulfan 4 mg/kg 2 days). Immunosuppressive therapy included the administration of antithymocyte globulin and post-transplant cyclophosphamide. Severe acute GVHD (grade 34) was observed in 3 (37.5%) cases, which resulted in death in 1 case. A stable antitumor response was achieved in 5 (62.5%) patients, complete remission lasts for 2986 months after allo-HSCT. Specific therapy for these patients is not carried out. The 7-year progression-free survival rate was 75%, the 7-year overall survival rate was 84%, with a median follow-up of 65 months. The transplant-related mortality was 12.5%. Allo-HSCT is considered as an alternative method of therapy for young patients with aggressive MM. Allo-HSCT in MM in some cases leads to long-term immunological control of the tumor.


Synthesis and characterization of 5-cyanotetrazolide-based ionic liquids.
New salts based on imidazolium, pyrrolidinium, phosphonium, guanidinium, and ammonium cations together with the 5-cyanotetrazolide anion [C2 N5 ](-) are reported. Depending on the nature of cation-anion interactions, characterized by XRD, the ionic liquids (ILs) have a low viscosity and are liquid at room temperature or have higher melting temperatures. Thermogravimetric analysis, cyclic voltammetry, viscosimetry, and impedance spectroscopy display a thermal stability up to 230 °C, an electrochemical window of 4.5 V, a viscosity of 25 mPa s at 20 °C, and an ionic conductivity of 5.4 mS cm(-1) at 20 °C for the IL 1-butyl-1-methylpyrrolidinium 5-cyanotetrazolide [BMPyr][C2 N5 ]. On the basis of these results, the synthesized compounds are promising electrolytes for lithium-ion batteries.


A Randomized Comparison of Clothing Removal Techniques in a Simulated Trauma Patient Exposure.
Introduction Trauma shears are commonly used by emergency medical services (EMS) providers to remove clothing from patients and expose underlying traumatic injuries. Other tools exist that may be more effective, but they are largely untested. This study compared the use of trauma shears versus two cutting hooks in removing clothing from a simulated trauma patient. Methods We recruited 18 paramedic students to participate in a cross-over study designed to remove clothing from a wholly dressed full-body training mannequin using trauma shears (with the cut-and-rip (CAR) technique) and two cutting hooks (S-Cut QE (ES Equipment AB, Nol, Sweden) and the Talon Rescue Emergency Clothing Knife (TRECK+, Talon Rescue, Farmington, CT, USA)). We determined the order of the tools using a three-by-three Latin square and randomized participants equally between possible orders to minimize carryover effects. We recorded times for total clothing removal and the removal of clothing from the upper and lower body, respectively. We employed a mixed-effects analysis of variance (ANOVA) to determine any differences between tools. Results Removal time was significantly faster with the S-Cut QE compared to the CAR technique and TRECK+ (mean 78 seconds, 95% confidence interval (CI) 52-103 vs. 142 seconds, 95% CI 117-167, vs. 209 seconds, 95% CI 184-235, p<0.001). The S-Cut QE was significantly faster than the CAR technique and TRECK+ for upper body clothing removal (mean 47 seconds, 95% CI 30-64 vs. 92 seconds, 95% CI 75-109, vs. 131 seconds, 95% CI 115-148, p<0.001) and the S-Cut QE and CAR were significantly faster than TRECK+ for lower body clothing removal (mean 25 seconds, 95% CI 11-38 and 44 seconds, 95% CI 31-58 vs. 71 seconds, 95% CI 58-85, p<0.001). Most (78%) participants preferred the S-Cut QE over other tools. Conclusion The S-Cut QE removed clothing from a simulated trauma patient faster than both the CAR and TRECK+. Emergency medical services (EMS) agencies should consider adding a cutting hook to their standard trauma kit.


Therapeutic T cell engineering.
Genetically engineered T cells are powerful new medicines, offering hope for curative responses in patients with cancer. Chimaeric antigen receptors (CARs) are a class of synthetic receptors that reprogram lymphocyte specificity and function. CARs targeting CD19 have demonstrated remarkable potency in B cell malignancies. Engineered T cells are applicable in principle to many cancers, pending further progress to identify suitable target antigens, overcome immunosuppressive tumour microenvironments, reduce toxicities, and prevent antigen escape. Advances in the selection of optimal T cells, genetic engineering, and cell manufacturing are poised to broaden T-cell-based therapies and foster new applications in infectious diseases and autoimmunity.


Gender Differences in Idiopathic Pulmonary Fibrosis: Are Men and Women Equal?
Background: Idiopathic pulmonary fibrosis (IPF) is characterized by a male predominance. The aim of the study was to explore gender differences in a well-designed French multicentre prospective IPF cohort (COhorte FIbrose, COFI) with a 5-year follow-up. Methods: Between 2007 and 2010, 236 patients with incident IPF were included in COFI. Gender characteristics were compared using a t-test, Chi-squared test and ANOVA, as appropriate. Survival analyses were performed. Results: Fifty-one (22%) females and 185 (78%) males with an average age at diagnosis of 70.1 ± 9.20 and 67.4 ± 10.9 years, respectively, were included in the cohort. Women were significantly less exposed to tobacco smoke [never n = 32 (62.7%) vs. n = 39 (21.1%), p < 0.001] and to occupational exposure [n = 7 (13.7%) vs. n = 63 (34.1%), p = 0.012]. Baseline forced vital capacity, % of predicted (FVC%) was significantly better in women compare to men (83.0% ± 25.0 v. 75.4% ± 18.7 p = 0.046). At presentation honeycombing and emphysema on CT scan were less common in women [n = 40 (78.4%) vs. n = 167 (90.3%) p = 0.041] and [n = 6 (11.8%) vs. n = 48 (25.9%) p = 0.029], respectively. During follow-up fewer women were transplanted compared to men [n = 1 (1.96%) vs. n = 20 (10.8%) p = 0.039]. Medians of survival were comparable by gender [31 months (CI 95%: 28-40) vs. 40 months (CI 95%: 33-72) p = 0.2]. After adjusting for age and FVC at inclusion, being a woman was not associated to a better survival. Conclusions: Women appear to have less advanced disease at diagnosis, maybe due to less exposure history compare to men. Disease progression and overall survival remains comparable regardless gender, but women have less access to lung transplantation.


Polybrominated diphenyl ethers (PBDEs) levels in blood samples from children living in the metropolitan area of Guadalajara, Jalisco, Mexico.
The aim of this study was to perform a polybrominated diphenyl ethers (PBDEs) exposure assessment using blood samples collected from children living in the metropolitan area of Guadalajara, Jalisco, Mexico (GDL). Five congeners of PBDEs were analyzed using a gas chromatography/mass spectrometry technique. The blood concentrations of total PBDEs ranged from 5.50 to 169 ng/g lipid (42.0 ± 18.0 ng/g lipid; mean ± standard deviation). Regarding BDE congeners, the main congener (highest blood levels) was BDE99 (14.5 ± 5.50 ng/g lipid), followed by BDE100 (9.80 ± 3.40 ng/g lipid) and BDE154 (9.80 ± 5.90 ng/g lipid), and finally BDE153 (5.80 ± 2.30 ng/g lipid) and BDE47 (2.20 ± 1.20 ng/g lipid). In conclusion, blood PBDEs concentrations of concern were detected in this study, as blood levels were similar to the ones found in North America (the highest worldwide).


Infectious Complications After Open Cranial Vault Remodeling for Craniosynostosis.
Surgical site infection (SSI) after open cranial vault reconstruction (CVR), while relatively uncommon, has received little attention in the literature to date. Here, the authors report our institution's experience with the perioperative management of infectious complications following CVR for craniosynostosis and present the first systematic review of the literature on this topic. The authors performed a retrospective chart review for patients with syndromic and nonsyndromic craniosynostosis who underwent open CVR between 1990 and 2015 at a single institution to determine predictors of SSIs and a systematic review of studies that evaluated for SSI after CVR to ascertain the pooled incidence of SSI, common infectious organisms, and prophylactic antibiotic protocols. Out of 548 primary and 163 secondary CVR cases at our institution, 6 primary reconstruction patients (1.09%) and 9 secondary reconstruction patients (5.52%) developed an SSI requiring extended hospital stay or readmission (P <0.001); overall infection rate was 2.11%. Streptococcus and Staphylococcus species were the most common organisms isolated. On multivariate analysis, syndromic status conferred more than 7 times greater odds of SSI (OR 7.7, P = 0.023). Pooled analysis of the literature yielded an overall SSI rate of 1.05% to 2.01%. In contrast to our institutional findings, the most common organisms reported were Candida species and Pseudomonas aeruginosa. The most common prophylactic antibiotic protocol was a first-generation cephalosporin for 24 to 72 hours post-operatively. Patients undergoing secondary reconstruction have higher infection rates after CVR, and syndromic status is an important predictor of infection when controlling for other patient factors. Our literature review reveals nosocomial organisms to be the most commonly reported source of infection, though this is contrary to our institutional findings of skin flora being most common. Antibiotic prophylaxis varies institutionally.


PET imaging in glioma: techniques and current evidence.
PET holds potential to provide additional information about tumour metabolic processes, which could aid brain tumour differential diagnosis, grading, molecular subtyping and/or the distinction of therapy effects from disease recurrence. This review discusses PET techniques currently in use for untreated and treated glioma characterization and aims to critically assess the evidence for different tracers ([F]Fluorodeoxyglucose, choline and amino acid tracers) in this context.


Pain Control in Total Knee Arthroplasty.
As surgical techniques and pharmacology advance, the management of postoperative pain in patients undergoing total knee arthroplasty (TKA) continues to evolve. The current standards of care are composed of multimodal pain management including opioids, nonsteroidal anti-inflammatory drugs and gabapentinoids, peripheral nerve blocks, and periarticular injections. Newer modalities are composed of delayed release local anesthetics and cryoneurolysis. To summarize the current evidence-based treatment modalities and forecast changes in the management of patients having TKAs, we reviewed available data on: (1) oral analgesics; (2) periarticular injections; (3) peripheral nerve blocks; (4) multimodal regimens; and (5) newer modalities in post-TKA pain management. Multimodal analgesic regimens that target numerous pain pathways may provide the best pain management, rehabilitation, patient satisfaction, and reduce opioid use and related side effects. Periarticular injections of delayed-release local anesthetics may further enhance pain management.


Small cell carcinomas and large cell neuroendocrine carcinomas of the endometrium and cervix: polypoid tumors and those arising in polyps may have a favorable prognosis.
We report 5 polypoid high-grade neuroendocrine carcinomas of the uterus, 2 small cell carcinomas of the endometrium, and 3 large cell neuroendocrine carcinomas, 2 from the cervix and 1 from the endometrium. The 2 small cell carcinomas of the endometrium arose from and were confined to endometrial polyps, one of which also showed foci of endometrioid adenocarcinoma. The myometrium was free of tumor, despite extensive sampling. The 3 large cell neuroendocrine carcinomas, 2 from the cervix and 1 from the endometrium, were polypoid but did not originate in polyps. Two of these tumors infiltrated myometrium, and one did not. The age of the 5 patients ranged from 25 to 66 years (mean age, 43 years). Four patients presented with vaginal bleeding. One pregnant woman had the largest polypoid tumor discovered during a routine gynecologic examination. Tumor sizes ranged from 2.7 to 10 cm. All 5 patients were treated by radical hysterectomy and 4 received adjuvant chemotherapy. Only 2 patient had pelvic lymph node metastasis. All patients are alive and disease-free from 9 months to 7 years after treatment (mean survival, 47 months). All 5 tumors labeled with chromogranin and synaptophysin and 4 with CD56. Two small cell carcinomas and 2 large cell neuroendocrine carcinomas accumulated p53 protein. Two small cell carcinomas and 2 large cell neuroendocrine carcinomas expressed p16. Our findings suggest that stage of disease and a polypoid gross feature are the best predictors for outcome in small cell carcinomas and large cell neuroendocrine carcinomas of the uterus.


Development and performance of a microwell-plate-based polymerase chain reaction assay for Mycoplasma genitalium.
Mycoplasma genitalium is associated with, and could be the cause of, idiopathic cases of urethritis, endometritis, and cervicitis. Further epidemiologic studies on this organism are needed, but currently used polymerase chain reaction (PCR) assays are labor-intensive and culture is insensitive. The goal was to develop and evaluate a microwell-plate-based PCR assay for M. genitalium. We adapted an M. genitalium PCR assay targeting the MgPa gene to a 96-microwell plate format with colorimetric detection of PCR products and incorporation of an internal inhibition control to determine the limit of detection of this assay (termed MgPa-IMW) for M. genitalium DNA and evaluate its performance on cervical and male urine specimens. The MgPa-IMW PCR assay detected 1 and 17 genome copies of M. genitalium (with 27% and 95% confidence) and was able to detect specimens inhibited for amplification. This assay was 100% concordant (50 positive and 50 negative) with the Southern-blot-based PCR assay with cervical specimens. Similarly, this test was 89% concordant with the Southern-blot-based assay for 64 male urine specimens (25 positive, 32 negative, 7 discordant), 97% concordant after correcting for specimens no longer positive by the Southern blot-based assay after freezer storage. The MgPa-IMW assay is sensitive and specific for the detection of M. genitalium in patient specimens and should facilitate large-scale screening for this organism.


Surgical treatment of traumatic anterior shoulder instability in american football players.
American football players have been reported to be at high risk for postoperative instability after arthroscopic stabilization of anterior shoulder instability. While some authors have recommended open methods of stabilization in athletes who play contact sports, there are few data in the literature showing more favorable results with use of an open technique. We reviewed the results of an open technique of anterior shoulder stabilization in fifty-eight American football players after a minimum of two years of follow-up. Fifty-eight American football players underwent open stabilization with use of a standardized technique for the treatment of recurrent anterior shoulder instability. Forty-seven patients had recurrent dislocations, and the remaining eleven had recurrent subluxations. The average age of the patients was 18.2 years, and the average duration of follow-up was thirty-seven months. Patients were evaluated according to the shoulder scoring system of the American Shoulder and Elbow Surgeons and with use of the shoulder instability score described by Rowe and Zarins. There were no postoperative dislocations. Postoperative subluxation occurred in two patients, neither of whom had had a dislocation prior to the operation. Forward flexion and external rotation returned to within 5 of those of the contralateral shoulder in forty-nine patients. The average score according to the system of the American Shoulder and Elbow Surgeons was 97.0 points, and the average Rowe and Zarins score was 93.6 points. Fifty-five patients had a good or excellent result, and fifty-two of the fifty-eight returned to playing football for at least one year. One patient was forced to stop playing because of recurrent instability. Open stabilization is a predictable method of restoring shoulder stability in American football players while maintaining a range of motion approximating that found after arthroscopic stabilization. Postoperative stability appears to be superior to that reported after arthroscopic techniques in this population of patients.


Menaquinone-4 accumulation in various tissues after an oral administration of phylloquinone in Wistar rats.
The distributions of phylloquinone (PK) and menaquinone-4 (MK-4) in various tissues were assessed after the oral administration of phylloquinone. Wistar rats were fed a vitamin-K-deficient diet for nine days, fasted for 24 h and then given phylloquinone orally at 4 mg/kg body weight. Rats were sacrificed 0, 6, 12 and 24 h after the administration, and an analysis was made of the vitamin K analogues in the plasma, liver, brain, testis, kidney and spleen. The phylloquinone concentration in plasma and the tissues reached a peak 6 h after the oral administration of phylloquinone. By contrast, the concentration of MK-4 peaked in the liver, plasma, kidney and spleen at 12 h, and in brain and testis at 24 h. This data suggests that the ingested phylloquinone was probably converted into MK-4 within the tissues themselves, rather than via hepatic metabolism. The evidence for this is that, after phylloquinone administration, (i) in each of the tissues, the MK-4 concentration increased much more slowly than that of phylloquinone, and (ii) the MK-4 concentration in the plasma and liver reached only much lower levels than those seen in other tissues.


[The efficacy of rheopolyglucin-based blood correctors in acute blood loss in rats].
The efficacy of rheopolyglucin and complex blood correctors based on it was demonstrated in experiments on 86 albino male rats. The main renal functions (glomerular filtration and tubular secretion), determined by radionuclide methods, were restored by means of infusion therapy. The effect was produced by the complex action exerted on the main pathogenetic mechanisms of the process. Rheopolyglucin injected into intact rats and rats subjected to blood loss led to a certain increase of the blood histamine level, but did not induce a shock-like reaction. Infusion of an equal volume of isotonic sodium chloride solution was also accompanied with hyperhistaminemia in some of the rats.


Hypnosis for schizophrenia.
Many people with schizophrenia continue to experience symptoms despite the use of conventional treatments. Alternative therapies such as hypnosis, in conjunction with conventional treatments, may prove beneficial to them. To investigate the use of hypnosis for people with schizophrenia or schizophrenia-like illnesses compared to standard care and other interventions. We searched the Cochrane Schizophrenia Group's Register (January 2003), contacted the Cochrane Complementary Medicine Field for additional searching, hand searched references of included or excluded studies and made personal contact with authors of relevant trials. All randomised or double blind controlled trials that compared hypnosis with other treatments or standard care for people with schizophrenia. Studies were reliably selected, quality assessed and data extracted. Data were excluded where more than 50% of participants in any group were lost to follow up. For binary outcomes we calculated a fixed effects risk ratio (RR) and its 95% confidence interval (CI). We included three studies (total n=149). When hypnosis was compared with standard treatment no one left between 1-8 weeks (n=70, 2 RCTs, Risk Difference 0.00 CI -0.09 to 0.09). Mental state scores were unaffected (n=60, 1 RCT, MD BPRS by 1 week -3.6 CI -12.05 to 4.8) as were measures of movement disorders and neurocognitive function. Compared with relaxation, hypnosis was also acceptable (n=106, 3 RCTs, RR leaving the study early 2.00 CI 0.2 to 2.15) and had no discernable effect on mental state (n=60, 1 RCT, MD BPRS by 1 week -3.4 CI -11.4 to 4.6), movement disorders or neurocognitive function. Hypnosis was as acceptable as music (Sibelius) by 4 weeks (n=36, RR leaving the study early 5.0, CI 0.3 to 97.4). The studies in this field are few, small, poorly reported and outdated. Hypnosis could be helpful for people with schizophrenia but to ascertain this requires better designed, conducted and reported randomised studies.


Pulsed nanogenerator with huge instantaneous output power density.
A nanogenerator (NG) usually gives a high output voltage but low output current, so that the output power is low. In this paper, we developed a general approach that gives a hugely improved instantaneous output power of the NG, while the entire output energy stays the same. Our design is based on an off-on-off contact based switching during mechanical triggering that largely reduces the duration of the charging/discharge process, so that the instantaneous output current pulse is hugely improved without sacrificing the output voltage. For a vertical contact-separation mode triboelectric NG (TENG), the instantaneous output current and power peak can reach as high as 0.53 A and 142 W at a load of 500 Ω, respectively. The corresponding instantaneous output current and power density peak even approach 1325 A/m(2) and 3.6 × 10(5) W/m(2), which are more than 2500 and 1100 times higher than the previous records of TENG, respectively. For the rotation disk based TENG in the lateral sliding mode, the instantaneous output current and power density of 104 A/m(2) and 1.4 × 10(4) W/m(2) have been demonstrated at a frequency of 106.7 Hz. The approach presented here applies to both a piezoelectric NG and a triboelectric NG, and it is a major advance toward practical applications of a NG as a high pulsed power source.


Valproic acid inhibits proliferation of HER2-expressing breast cancer cells by inducing cell cycle arrest and apoptosis through Hsp70 acetylation.
Breast cancer encompasses a heterogeneous group of diseases at the molecular level. It is known that chemosensitivity of breast cancer depends on its molecular subtype. We investigated the growth inhibitory effect of valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, and the mechanism of this inhibition on four breast cancer cell lines with different molecular subtypes. The growth inhibitory effect of VPA in the four different breast cancer cell lines was investigated. The alteration of levels of p21 WAF1, cleaved caspase-3, acetylated Heat shock protein (Hsp) 90, acetylated Hsp70, and acetylated α-tubulin by VPA was examined in VPA-sensitive, human epidermal receptor 2 (HER2)-overexpressing SKBR3 cells. The cell growth inhibition of breast cancer cell lines was dependent on the dose and exposure time of VPA. The cell growth of HER2-overexpressing SKBR3 cell line was inhibited by VPA to a much greater degree than other cell lines studied. In SKBR3 cell line, VPA upregulated expression of p21 WAF1 and cleaved caspase-3 in the early phase. VPA markedly increased Hsp70 acetylation in a time-dependent manner but did not increase Hsp90 acetylation. Our data demonstrated that VPA inhibited cell proliferation and induced cell cycle arrest and apoptosis of HER2-overexpressing breast cancer cells. This anti-proliferation effect might be the direct function of VPA as an HDAC inhibitor. We propose an alternative mechanism whereby acetylation of Hsp70 disrupts the function of Hsp90 and leads to downregulation of its client proteins, including HER2 that might be the indirect function of VPA, in the sense that non-histone proteins are acetylated.


Apoptosis of Kinetin Riboside in Colorectal Cancer Cells Occurs by Promoting β-Catenin Degradation.
Kinetin riboside is a naturally produced cytokinin that displays strong antiproliferative activity in various human cancer cells. However, the mechanism of chemoprevention in colorectal cancer cells has not been elucidated. We used a cell-based reporter system to identify kinetin riboside as an antagonist of the Wnt/β-catenin pathway, which is aberrantly upregulated in colorectal cancer. Kinetin riboside suppressed β-catenin response transcription (CRT) by accelerating the degradation of intracellular β-catenin via a proteasomal degradation pathway. Pharmacological inhibition of glycogen synthase kinase-3β did not affect CRT downregulation. Kinetin riboside decreased the intracellular β-catenin levels in colorectal cancer cells with mutations in adenomatous polyposis coli (APC) and β-catenin. Consistently, kinetin riboside repressed expression of c-Myc and cyclin D1, β-catenin/T-cell factor (TCF)-dependent genes, and inhibited the proliferation of colorectal cancer cells. In addition, kinetin riboside stimulated apoptosis, as measured by an increase in annexin V-FITC-stained cells. These findings suggest that kinetin riboside exerts its anti-cancer activity by promoting β-catenin degradation and has significant potential as a chemopreventive agent for colorectal cancer cells.


Cellular/molecular control of renal Na/Pi-cotransport.
A type II Na/Pi-cotransporter located in the brush border membrane is the rate limiting and physiologically regulated step in proximal tubular phosphate (Pi) reabsorption. In states of altered Pi-reabsorption [for example, in response to parathyroid hormone (PTH) and to altered dietary intake of Pi or as a consequence of genetic abnormalities], brush border expression of the type II Na/Pi-cotransporter is accordingly modified. PTH initiates a regulatory cascade leading to membrane retrieval, followed by lysosomal degradation of this transporter; recovery from inhibition requires its de novo synthesis. Pi-deprivation leads to an increased brush border expression of transporters that does not appear to require de novo synthesis in the short term. Pi-overload leads to membrane retrieval and degradation of transporters. Finally, in animals with genetically altered Pi-handling (Hyp; Gy) the brush border membrane expression of the type II Na/Pi-cotransporter is also reduced, suggesting that a genetically altered protein (such as PEX in Hyp) controls the expression of this transporter.


Course of the fatigue dimension "activity level" and the interference of fatigue with daily living activities for patients with breast cancer receiving adjuvant chemotherapy.
The purpose of this study was to determine the course of the activity level, seen as a dimension of fatigue, as a function of chemotherapy within a breast cancer population receiving adjuvant chemotherapy. The second purpose of this study was to determine the course of the interference of fatigue, in general, with daily activities within a breast cancer population receiving adjuvant chemotherapy. In a prospective cohort study, a sample of 157 patients with breast cancer was interviewed, at the first, third, and fifth cycle of adjuvant chemotherapy as well as 4 and 12 weeks after the last cycle of adjuvant chemotherapy. The chemotherapy was administered with either a doxorubicin-containing schedule or cyclophosphamide, methotrexate, and 5-fluorouracil. These 2 groups were compared. The activity level was measured by the Multidimensional Fatigue Inventory. A linear multilevel model was used to analyze the course. The revised Piper Fatigue Scale was used to examine the behavioral changes in the interference of fatigue with activities of daily living. A logistic multilevel model was used to analyze the course of this interference over time. The activity level seems to be rather stable during the treatment with chemotherapy. After the completion of chemotherapy, an improvement is observed. The activity levels reported at the first and the last measurement do not significantly differ. The course of the activity level is not affected by the type of chemotherapy regimen. Age, having children, and the stage of breast cancer turn out to be important determinants of the course of activity level. At all measurement occasions, women with a mastectomy were significantly more hampered in their activity level than women that had undergone a lumpectomy. The longer the duration of radiotherapy, the less active, and the longer the time interval between the last radiotherapy session and the measurement point, the more active patients were at that measurement point. A phenomenon not easy to explain is that the activity level in women who had received, in total, more chemotherapy treatments was significantly less diminished than those who had received fewer treatments. During the study period, in approximately 15% to 35% of the sample, fatigue interferes considerably with their daily living activities. Furthermore, the interference of fatigue with activities in daily life first increases after the start of chemotherapy and decreases after the completion of chemotherapy. Fatigue definitely affects the daily living activities of patients with breast cancer receiving adjuvant chemotherapy. With this knowledge, healthcare providers can inform patients on what they can expect. Further research should include the trajectory preceding chemotherapy and a healthy control group.


Validating and improving CT ventilation imaging by correlating with ventilation 4D-PET/CT using 68Ga-labeled nanoparticles.
CT ventilation imaging is a novel functional lung imaging modality based on deformable image registration. The authors present the first validation study of CT ventilation using positron emission tomography with (68)Ga-labeled nanoparticles (PET-Galligas). The authors quantify this agreement for different CT ventilation metrics and PET reconstruction parameters. PET-Galligas ventilation scans were acquired for 12 lung cancer patients using a four-dimensional (4D) PET/CT scanner. CT ventilation images were then produced by applying B-spline deformable image registration between the respiratory correlated phases of the 4D-CT. The authors test four ventilation metrics, two existing and two modified. The two existing metrics model mechanical ventilation (alveolar air-flow) based on Hounsfield unit (HU) change (VHU) or Jacobian determinant of deformation (VJac). The two modified metrics incorporate a voxel-wise tissue-density scaling (ρVHU and ρVJac) and were hypothesized to better model the physiological ventilation. In order to assess the impact of PET image quality, comparisons were performed using both standard and respiratory-gated PET images with the former exhibiting better signal. Different median filtering kernels (σm = 0 or 3 mm) were also applied to all images. As in previous studies, similarity metrics included the Spearman correlation coefficient r within the segmented lung volumes, and Dice coefficient d20 for the (0 - 20)th functional percentile volumes. The best agreement between CT and PET ventilation was obtained comparing standard PET images to the density-scaled HU metric (ρVHU) with σm = 3 mm. This leads to correlation values in the ranges 0.22 ≤ r ≤ 0.76 and 0.38 ≤ d20 ≤ 0.68, with r = 0.42 ± 0.16 and d20 = 0.52 ± 0.09 averaged over the 12 patients. Compared to Jacobian-based metrics, HU-based metrics lead to statistically significant improvements in r and d20 (p < 0.05), with density scaled metrics also showing higher r than for unscaled versions (p < 0.02). r and d20 were also sensitive to image quality, with statistically significant improvements using standard (as opposed to gated) PET images and with application of median filtering. The use of modified CT ventilation metrics, in conjunction with PET-Galligas and careful application of image filtering has resulted in improved correlation compared to earlier studies using nuclear medicine ventilation. However, CT ventilation and PET-Galligas do not always provide the same functional information. The authors have demonstrated that the agreement can improve for CT ventilation metrics incorporating a tissue density scaling, and also with increasing PET image quality. CT ventilation imaging has clear potential for imaging regional air volume change in the lung, and further development is warranted.


Frequency of dream sharing: the effects of gender and personality.
Although dreaming is a private experience, dream sharing is a common experience for most people. Dreams are disclosed to romantic partners, friends, and relatives, and the sharing is often associated with enhancement of relational intimacy and stress relief (e.g., in the case of nightmares). Research has focused on factors that might affect dream sharing such as dream recall frequency, gender, and emotional intensity of the dream. The present findings indicate that about 14.5% of the dreams were shared and that dream recall frequency, nightmare frequency, attitude toward dreams, gender, extroversion, and thin boundaries are associated independently with the frequency of dream sharing. Longitudinal studies are needed to differentiate between state factors and trait factors and to validate the self-reported positive effects of dream sharing on intimacy in romantic relationships and friendships.


Anti-allodynic efficacy of the chi-conopeptide, Xen2174, in rats with neuropathic pain.
Xen2174 is a structural analogue of Mr1A, a chi-conopeptide recently isolated from the venom of the marine cone snail, Conus marmoreus. Although both chi-conopeptides are highly selective inhibitors of the norepinephrine transporter (NET), Xen2174 has superior chemical stability relative to Mr1A. It is well-known that tricyclic antidepressants (TCAs) are also potent NET inhibitors, but their poor selectivity relative to other monoamine transporters and various G-protein-coupled receptors, results in dose-limiting side-effects in vivo. As TCAs and the alpha(2)-adrenoceptor agonist, clonidine, have established efficacy for the relief of neuropathic pain, this study examined whether intrathecal (i.t.) Xen2174 alleviated mechanical allodynia in rats with either a chronic constriction injury of the sciatic nerve (CCI-rats) or an L5/L6 spinal-nerve injury. The anti-allodynic responses of i.t. Mr1A and i.t. morphine were also investigated in CCI-rats. Paw withdrawal thresholds were assessed using calibrated von Frey filaments. Bolus doses of i.t. Xen2174 produced dose-dependent relief of mechanical allodynia in CCI-rats and in spinal nerve-ligated rats. Dose-dependent anti-allodynic effects were also produced by i.t. bolus doses of Mr1A and morphine in CCI-rats, but a pronounced 'ceiling' effect was observed for i.t. morphine. The side-effect profiles were mild for both chi-conopeptides with an absence of sedation. Confirming the noradrenergic mechanism of action, i.t. co-administration of yohimbine (100 nmol) with Xen2174 (10 nmol) abolished Xen2174s anti-allodynic actions. Xen2174 appears to be a promising candidate for development as a novel therapeutic for i.t. administration to patients with persistent neuropathic pain.


Orthorhombic C32: a novel superhard sp3 carbon allotrope.
Using a recently developed 'Crystal structure AnaLYsis by Particle Swarm Optimization' (CALYPSO) algorithm on a structural search, we predicted a novel sp(3) carbon allotrope possessing an orthorhombic lattice with the space group Cmmm (oC32). The calculated elastic constants and the simulated hardness revealed that oC32 simultaneously possesses ultra-incompressible and superhard properties with a high bulk modulus of 457 GPa and a high Vickers hardness of 96.2 GPa. This oC32 phase is dynamically stable and energetically more preferable than the experientially observed cold-compressed carbon, thus oC32 is expected to be experimentally synthesizable under extreme conditions. These results further expand the list of meta-stable carbon allotropes and superhard materials under atmospheric and extreme conditions.


Synthesis and supramolecular self-assembly of coil-rod-coil molecules: the relationship between self-assembled nanostructures and molecular structures.
Herein, the relationship between the supramolecularly self-assembled nanostructures and the chemical structures of coil-rod-coil molecules is discussed. A series of nonamphiphilic coil-rod-coil molecules with different alkyl chains, central mesogenic groups, and chemical linkers were designed and synthesized. The solvent-mediated supramolecular self-assembling of these coil-rod-coil molecules resulted in rolled-up nanotubes, nanofibers, submicron sized belts, needle-like microcrystals, and amorphous structures. The self-assembling behaviors of these coil-rod-coil molecules have been systematically investigated to reveal the relationship between the supramolecularly self-assembled nanostructures and their chemical structures. With respect to the formation of rolled-up nanotubes by self-assembly of coil-rod-coil molecules, we have systematically investigated the following three influencing structural factors: 1) the alkyl chain length; 2) the central mesogenic group; (3) the linker type. These studies disclosed the key structural features of coil-rod-coil molecules for the formation of rolled-up nanotubes.


Injection of ultrasmall samples and single molecules into tapered capillaries.
A novel injection scheme is described in which ultrasmall samples in the attoliter (10(-18) L) and low femtoliter (10(-15) L) range, or even single molecules, are controllably introduced into a tapered capillary so that electrophoretic separation can be carried out. To match the dimensions of the capillary inlet with that of the sample, capillary tips are tapered to an inside diameter ranging from hundreds of nanometers to a few micrometers. To inject an ultrasmall sample, optical trapping is used to immobilize and manipulate the sample in order to place it inside or next to the capillary inlet. A small controlled suction results in the loading of the sample into the capillary.


Experimental transmission of ovine atypical scrapie to cattle.
Classical bovine spongiform encephalopathy (BSE) in cattle was caused by the recycling and feeding of meat and bone meal contaminated with a transmissible spongiform encephalopathy (TSE) agent but its origin remains unknown. This study aimed to determine whether atypical scrapie could cause disease in cattle and to compare it with other known TSEs in cattle. Two groups of calves (five and two) were intracerebrally inoculated with atypical scrapie brain homogenate from two sheep with atypical scrapie. Controls were five calves intracerebrally inoculated with saline solution and one non-inoculated animal. Cattle were clinically monitored until clinical end-stage or at least 96 months post-inoculation (mpi). After euthanasia, tissues were collected for TSE diagnosis and potential transgenic mouse bioassay. One animal was culled with BSE-like clinical signs at 48 mpi. The other cattle either developed intercurrent diseases leading to cull or remained clinical unremarkable at study endpoint, including control cattle. None of the animals tested positive for TSEs by Western immunoblot and immunohistochemistry. Bioassay of brain samples from the clinical suspect in Ov-Tg338 and Bov-Tg110 mice was also negative. By contrast, protein misfolding cyclic amplification detected prions in the examined brains from atypical scrapie-challenged cattle, which had a classical BSE-like phenotype. This study demonstrates for the first time that a TSE agent with BSE-like properties can be amplified in cattle inoculated with atypical scrapie brain homogenate.


Transcatheter arterial chemoembolization in cytoreduction of inoperable hepatocarcinomas.
Transcatheter arterial chemoembolization (TAE) is often considered a mean of palliation for inoperable liver carcinomas. A few centers use a sequential treatment (TAE followed by surgery). However the role of TAE in bringing to surgery patients with hepatocarcinomas (HCC) considered inoperable at first diagnosis is debated. We report on the case of a 57 y.o. male diagnosed as having HCC, inoperable because of bilateral location and size. The patient was treated with repeated TAEs and the results were monitored with CT scans. After three TAEs, the main tumor mass volume was reduced 2.2 fold and the patient could undergo surgery; the postoperative period was uneventful, with no clinical signs of liver failure. Our experience leads us to suggest that TAE, further to being an option for palliation, can be a valuable tool to lead to surgery otherwise inoperable HCC patients.


Effects of Traumatic Stress Induced in the Juvenile Period on the Expression of Gamma-Aminobutyric Acid Receptor Type A Subunits in Adult Rat Brain.
Studies have found that early traumatic experience significantly increases the risk of posttraumatic stress disorder (PTSD). Gamma-aminobutyric acid (GABA) deficits were proposed to be implicated in development of PTSD, but the alterations of GABA receptor A (GABAAR) subunits induced by early traumatic stress have not been fully elucidated. Furthermore, previous studies suggested that exercise could be more effective than medications in reducing severity of anxiety and depression but the mechanism is unclear. This study used inescapable foot-shock to induce PTSD in juvenile rats and examined their emotional changes using open-field test and elevated plus maze, memory changes using Morris water maze, and the expression of GABAAR subunits (γ2, α2, and α5) in subregions of the brain in the adulthood using western blotting and immunohistochemistry. We aimed to observe the role of GABAAR subunits changes induced by juvenile trauma in the pathogenesis of subsequent PTSD in adulthood. In addition, we investigated the protective effects of exercise for 6 weeks and benzodiazepine (clonazepam) for 2 weeks. This study found that juvenile traumatic stress induced chronic anxiety and spatial memory loss and reduced expression of GABAAR subunits in the adult rat brains. Furthermore, exercise led to significant improvement as compared to short-term BZ treatment.


Nocturnal Sleep Problems Mediate the Impact on Quality of Life of Early Morning Off in Parkinson's Disease.
Background: Early morning off (EMO) refers to off-states in the morning in people diagnosed with Parkinson's disease (PwPD). This study determined the clinical manifestations of EMO and the association with nocturnal sleep problems and quality of life (QOL) in Chinese PwPD. Methods: In this multicenter, observational, cross-sectional study, data concerning the clinical manifestations of EMO were collected from PwPD in Shanghai by questionnaire. The stepwise logistic regression was performed to analyze the potential risk factors, as well as whether EMO was an independent risk factor for functional dependency in daily life. The mediation analyses were conducted to evaluate whether nocturnal sleep problems might mediate the association between EMO and the QOL. Results: Among the 454 subjects evaluated, EMO occurred in 39.43% of PwPD across all disease stages. The prevalence of EMO increased as the Hoehn and Yahr stage increased and was observed in 35.60% of patients in stages 1-2.5 and 48.85% of patients in stages 3-5. EMO was associated with non-motor symptoms (NMSs). The predominant NMSs associated with EMO were nocturnal sleep problems (98.90%), mood/cognition impairment (93.90%), decreased attention/memory (91.60%), gastrointestinal symptoms (91.60%), and urinary urgency (90.50%). The QOL of PwPD with EMO was significantly reduced (P < 0.001). Moreover, nocturnal sleep problems might partially mediate this relationship (indirect effect: β = 13.458, 95% boot CI: 6.436, 22.042). Conclusion: PwPD have EMO throughout all stages of the disease. Patients with EMO have severe motor symptoms and NMSs. EMO decreases the QOL in PwPD and this relationship is partially mediated by nocturnal sleep problems. In light of these findings, it is suggested that recognition and appropriate treatment of EMO and nocturnal sleep problems could improve the management of PwPD.


New Scandium Borylimido Chemistry: Synthesis, Bonding, and Reactivity.
We report a combined synthetic, mechanistic, and theoretical study of the first borylimido complex of a rare earth metal, (NacNacNMe2)Sc{NB(NAr'CH)2} (25, Ar' = 2,6-C6H3iPr2, NacNacNMe2 = Ar'NC(Me)CHC(Me)NCH2CH2NMe2). Thermolysis of the methyl-borylamide (NacNacNMe2)Sc(Me){NHB(NAr'CH)2} (18) generated transient imide 25 via rate-determining, first-order methane elimination (KIE ≈ 8.7). In the absence of external substrate, 25 underwent a reversible cyclometalation reaction (sp3 C-H bond addition to Sc═Nimide) with a methyl group of the NacNacNMe2 ligand forming {MeC(NC6H3iPrCH(Me)CH2)CHC(Me)NCH2CH2NMe2}Sc{NHB(NAr'CH)2} (21). In the presence of pyridine or DMAP, reversible sp2 C-H bond activation occurred, forming orthometalated complexes (NacNacNMe2)Sc{NHB(NAr'CH)2}(η2-4-NC5H3R) (R = H or NMe2). In situ reaction of 25 with HCCTol gives irreversible sp C-H bond activation under kinetic control, and with MeCCPh [2+2] cycloaddition to Sc═Nimide takes place. These reactions represent the first substrate activation processes for any metal-bound borylimide. The bonding in 25 and the mechanism and thermodynamics of the reactions have been studied using density functional theory (DFT), supported by quantum theory of atoms in molecules and natural bond orbital analysis. Although the borylimido and arylimido dianions studied here are formally isoelectronic and possess comparable frontier molecular orbitals, the borylimido ligand is both a better π-donor and σ-donor, forming stronger and shorter metal-nitrogen bonds with somewhat reduced ionicity. Despite this, reactions of these types of borylimides with C-H or C≡C bonds are all more exothermic and more strongly activating than for the corresponding arylimides. DFT calculations on model systems of differing steric bulk unpicked the underlying thermodynamic factors controlling the reactions of 25 and its reaction partners, and a detailed comparison was made with the previously described arylimido homologues.


[Regulatory effect of electroacupuncture on heart and stomach of rats].
To explore different regulatory effects of electroacupuncture (EA) at the same acupoint on the heart and the stomach. Eighty male SD rats were randomly divided into eight groups equally, i.e., the Neiguan (PC6) group, the Quchi (LI11) group, the Tianshu (ST25) group, the Danzhong (RN17) group, the Zusanli (ST36) group, the Sanyinjiao (SP6) group, the Xinshu (BL15) group, and the Weishu (BL21) group, 10 in each group. The regulatory effects of EA (2/15 Hz, 3 mA, 2 min) at different acupoints on the gastric motility (intragastric pressure) and the cardiac function (the left ventricular pressure) were observed. The mean values of effect of two-min pre-EA and after-EA were compared. Compared with the pre-EA in the same group, the left ventricular pressure decreased in the Neiguan (PC6) group, the Quchi (LI11) group, the Danzhong (RN17) group, the Sanyinjiao (SP6) group, and the Xinshu (BL15) group (P <0.05). The intragastric pressure increased in the Quchi (LI11) group, the Zusanli (ST36) group, the Sanyinjiao (SP6) group, and the Xinshu (BL15) group, while it decreased in the Tianshu (ST25) group, the Danzhong (RN17) group, and the Weishu (BL21) group (P <0.05). The difference of the left ventricular pressure was sequenced from high to low as Xinshu (BL15) >Danzhong (RN17) >Neiguan (PC6) >Sanyinjiao (SP6) >Quchi (LI11). The difference of the intragastric pressure was sequenced from high to low as Tianshu (ST25) >Weishu (BL21) > Xinshu (BL15) > Danzhong (RN17) > Zusanli (ST36) > Sanyinjiao (SP6) > Quchi (LI11). EA at the same acupoint (2/15 Hz, 3 mA) showed different regulatory effects on the heart and stomach. There existed some difference in the direction and size due to the acupoint location, meridians, dominant nerve segment or relating organs. A fixed effect direction to the specific target was also shown.


Social, economic and operational research on tuberculosis: recent studies and some priority questions.
Social, economic and operational research has already contributed to the growing global awareness of the neglected burden of tuberculosis on individuals, families and communities. These studies have also illustrated that short-course chemotherapy for smear-positive pulmonary tuberculosis is a highly cost-effective tool for combatting tuberculosis. In the present work, the author examines the costs and effectiveness of the national tuberculosis programmes in Malawi, Mozambique and Tanzania. Chemotherapy for smear-positive tuberculosis is found to be among the most cost-effective health interventions known, costing 1-4 US dollars per year of life saved. In all situations, short-course chemotherapy is found to be more cost-effective than standard 12-month chemotherapy. General conclusions about the role of hospitalization are difficult to make; its cost-effectiveness depends on local patterns of compliance and the cost of hospitalization. Because more than three-quarters of the benefits of chemotherapy for smear-positive tuberculosis are due to transmission reduction, treating HIV sero-positives, smear-positives is probably cost-effective.


Scientific initiation in medical education.
It has been said that scientific initiation propagates the development of logical and critical thinking, instigates a commitment to life-long learning and stimulates the formation of new scientists. This essay describes the personal experience of the scientific initiation process of a medical student and reports on the impacts this extra-curricular activity has had over this student's graduation period.


High-resolution XANES studies on vanadium-containing haloperoxidase: pH-dependence and substrate binding.
High-resolution X-ray absorption vanadium K-edge spectra were recorded for samples of vanadium-containing bromoperoxidase from the brown alga, Ascophyllum nodosum, at pH 9, 7, 5 and 4, as well as for enzyme samples containing the substrates, hydrogen peroxide and bromide. The well-resolved features of the XANES spectra are discussed. The pH-dependence of the structure of the active site has been studied revealing no significant change of the absorption features. We were able to detect an interaction of H2O2 with the vanadium site of the bromoperoxidase using XAS spectroscopy, whereas addition of bromide causes no energy shift of the XANES spectrum. The possible role of vanadium during the enzymatic reaction is discussed on the basis of our results.