Cardiovascular Benefits of Dark Chocolate?
The use of cacao for health benefits dates back at least 3000 years. Our understanding of cacao has evolved with modern science. It is now felt based on extensive research the main health benefits of cacao stem from epicatechin, a flavanol found in cacao. The process of manufacturing dark chocolate retains epicatechin, whereas milk chocolate does not contain significant amounts of epicatechin. Thus, most of the current research studies are focused on dark chocolate. Both epidemiological and clinical studies suggest a beneficial effect of dark chocolate on blood pressure, lipids, and inflammation. Proposed mechanisms underlying these benefits include enhanced nitric oxide bioavailability and improved mitochondrial structure/function. Ultimately, further studies of this promising compound are needed to elucidate its potential for prevention and treatment of cardiovascular and metabolic diseases as well as other diseases that have underlying mechanisms of mitochondrial dysfunction and nitric oxide deficiency.


The influence of various amino acids on the extrahepatic bile ducts in newborn mice--an experimental study.
Excess proline in adult animals is associated with extrahepatic biliary hyperplasia. Possible therapeutic application of this amino acid in biliary atresia was postulated. In order to test whether excess proline had an influence on the development of the extrahepatic bile ducts, pregnant mice were injected daily with various amino acids. One day and 1 week after delivery, the extrahepatic bile ducts of the newborn mice were studied and the number of epithelial cells per cross section was determined. Neither proline nor any other amino acid had an influence on the proliferation of extrahepatic bile ducts.


Highly sensitive and quantitative biodetection with lipid-polymer hybrid nanoparticles having organic room-temperature phosphorescence.
A versatile organic room-temperature phosphorescence (RTP)-based "turn on" biosensor platform has been devised with high sensitivity by combining oxygen-sensitive lipid-polymer hybrid RTP nanoparticles with a signal-amplifying enzymatic oxygen scavenging reaction in aqueous solutions. When integrated with a sandwich-DNA hybridization assay on 96-well plates, our phosphorimetric sensor demonstrates sequence-specific detection of a cell-free cancer biomarker, a TP53 gene fragment, with a sub-picomolar (0.5 p.m.) detection limit. This assay is compatible with detecting cell-free nucleic acids in human urine samples. Simply by re-programming the detection probe, our unique methodology can be adapted to a broad range of biosensor applications for biomarkers of great clinical importance but difficult to detect due to their low abundance in vivo.


Study on the influences of ultrasound on the flavor profile of unsmoked bacon and its underlying metabolic mechanism by using HS-GC-IMS.
For exploring the influence of ultrasound on the flavor characteristic of unsmoked bacon, sensory evaluation combined with E-nose and headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS) were performed to analyze the overall flavor profile and specific volatile flavor compounds (VFCs), respectively. Furthermore, the metabolic pathway of VFCs affected by ultrasound was also investigated. Results demonstrated that ultrasound improved the flavor characteristic of unsmoked bacon by raising the levels of nonanal, heptanal, octanal, 3-methylbutanal n-hexyl acetate and n-propyl acetate. Enzymatic oxidation was found to be an important metabolic pathway responsible for the development of flavor characteristic after ultrasound treatment, which could be attributed to the increased activities of lipases and lipoxygenase and the higher concentration of polyunsaturated free fatty acids. The increased level of lipid oxidation after ultrasound treatment was also confirmed by thiobarbituric acid reactive substances. Consequently, ultrasound is an effective approach to enhance the flavor characteristic of unsmoked bacon.


Tubules invaginating from the sarcolemma in the subneural region of muscle fibers.
Sarcoplasmic tubules invaginating from the sarcolemma of the subneural region of muscle fibers are described in Atlantic hagfish and rat. In rat, the tubules invaginate from the bottoms of the secondary synaptic clefts. The density of tubule openings may be higher than the density of T-tubule openings elsewhere along muscle fibers.


Tamm-Horsfall protein is a marker of renal and extra-renal rhabdoid tumours.
A monoclonal antibody (MAb) to Tamm-Horsfall protein (THP) was used to stain 6 renal rhabdoid tumours (RRT) and 2 primary extra-renal rhabdoid tumours (E-RRT). One of the E-RRT was a tumour from the posterior fossa of a 3-year-old child and the other was a lump from the right side of the neck in an 18-month-old girl. Five of 6 RRT and both cases of E-RRT were positive for THP. Both cases of E-RRT also reacted with vimentin and cytokeratin MAbs. On electron microscopy, cells from both E-RRT were seen to contain concentric whorls of intermediate filaments characteristic of rhabdoid tumours. Viable tissues from one RRT and one E-RRT (the posterior fossa tumour) were available for tissue culture. Ninety-five percent of the cells growing out of both tumours were polygonal and approximately 5% of these cells were THP-positive.


Interprofessional In Situ Simulation to Identify Latent Safety Threats for Quality Improvement: A Single-Center Protocol Report.
In situ simulation has frequently been used to improve team performance and provide an opportunity for the practice of critical skills and identify latent safety threats, which are undetected risks that may lead to adverse outcomes. However, the use of known quality improvement tools to prioritize and mitigate these safety threats is an area requiring further study. Over the course of 9 in situ simulations of a pediatric shock case, postcase debriefs were held to identify latent safety threats in an emergency department and a mixed pediatric and adult inpatient unit. Latent safety threats identified included structure-related threats such as inability to locate critical equipment, knowledge-based threats relating to rapid intravenous fluid administration, and communication-based threats such as lack of role designation. Identification of latent safety threats in the health care environment may assist clinician leaders in mitigating risk of patient harm. The protocol described may be adopted and applied to other critical event simulations, with structured debriefing used as a tool to identify and mitigate threats before they affect the patient.


[Prevalence of dental caries in a school population of the Amazonian region].
In view of the lack of data as to the prevalence of dental caries among typical amazonian populations, the authors carried out an epidemiological study of 103 schoolchildren from Sirituba Island, Abaetetuba, Pará, Brazil. The mean values found for DMFT and deft were 6.5 and 5.4 respectively. Although the region is very primitive, this high prevalence may be linked to several factors, among which is the urban influence, mainly through the use of sugar, on food habits in such a way as fundamentally to alter the diet of the amazonian population.


DNMT3A-mediated high expression of circ_0057504 promotes benzo[a]pyrene-induced DNA damage via the NONO-SFPQ complex in human bronchial epithelial cells.
Benzo[a]pyrene (B[a]P) is a class I carcinogen and hazardous environmental pollutant with genetic toxicity. Understanding the molecular mechanisms underlying genetic deterioration and epigenetic alterations induced by environmental contaminants may contribute to the early detection and prevention of cancer. However, the role and regulatory mechanisms of circular RNAs (circRNAs) in the B[a]P-induced DNA damage response (DDR) have not been elucidated. In this study, human bronchial epithelial cell lines (16HBE and BEAS-2B) were exposed to various concentrations of B[a]P, and BALB/c mice were treated with B[a]P intranasally. B[a]P exposure was found to induce DNA damage and upregulate circular RNA hsa_circ_0057504 (circ_0057504) expression in vitro and in vivo. In addition, B[a]P upregulated TMEM194B mRNA and circ_0057504 expression through inhibition of DNA methyltransferase 3 alpha (DNMT3A) expression in vitro. Modulation (overexpression or knockdown) of circ_0057504 expression levels using a lentiviral system in human bronchial epithelial cells revealed that circ_0057504 promoted B[a]P-induced DNA damage. RNA pull-down and western blot assays showed that circ_0057504 interacted with non-POU domain-containing octamer-binding (NONO) and splicing factor proline and glutamine rich (SFPQ) proteins and regulated formation of the NONO-SFPQ protein complex. Thus, our findings indicate that circ_0057504 acts as a novel regulator of DNA damage in human bronchial epithelial cells exposed to B[a]P. The current study reveals novel insights into the role of circRNAs in the regulation of genetic damage, and describes the effect and regulatory mechanisms of circ_0057504 on B[a]P genotoxicity.


Endonuclease cleavage of DNA in the aged cochlea of Mongolian gerbil.
Apoptosis is the most common form of physiological cell death, plays an important role in a variety of physiological and pathological situations, and is characterized by an endonuclease activation. Aged gerbils (24-month-old) showed a significant elevation of the distortion product otoacoustic emission (DPOAE) threshold and a significant decrease of the DPOAE level as compared to young gerbils (3- to 6-month-old), suggesting a disturbance of the outer hair cell in the aged cochlea. Furthermore, the endocochlear potential in the aged (15-75 mV) was apparently lower than that in the young (80-90 mV), indicating strial damage with aging. A terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end-labeling (TUNEL) method demonstrated the presence of the DNA fragmentation predominantly in the outer hair cells and spiral ganglion cells. These changes were sporadically observed in the inner hair cells and supporting cells. TUNEL positive cells were markedly observed in some aged gerbils showing deterioration in cochlear function, which may suggest the individual variability of presbycusis. On the other hand, the strial cells showed a marked atrophy, but no DNA fragmentation. These findings suggest that the aged change in the outer hair cells and spiral ganglion cells involves an apoptotic death pathway. However, strial atrophy with aging seems to be unrelated to apoptosis.


The molecular mechanism of toxin-induced conformational changes in a potassium channel: relation to C-type inactivation.
Recently, a solid-state NMR study revealed that scorpion toxin binding leads to conformational changes in the selectivity filter of potassium channels. The exact nature of the conformational changes, however, remained elusive. We carried out all-atom molecular dynamics simulations that enabled us to cover the complete pathway of toxin approach and binding, and we validated our simulation results by using solid-state NMR data and electrophysiological measurements. Our structural model revealed a mechanism of cooperative toxin-induced conformational changes that accounts both for the signal changes observed in solid-state NMR and for the tight interaction between KcsA-Kv1.3 and Kaliotoxin. We show that this mechanism is structurally and functionally closely related to recovery from C-type inactivation. Furthermore, our simulations indicate heterogeneity in the binding modes of Kaliotoxin, which might serve to enhance its affinity for KcsA-Kv1.3 further by entropic stabilization.


Association between metal(loid)s in serum and leukemia: a systematic review and meta-analysis.
Heavy metals and metalloids are recognized as environmental threats, which are considered highly toxic and carcinogenic. Epidemiologically, their association with leukemia is under debate. We aim to clarify the association between the heavy metal(loid)s in serum and leukemia via a systematic review and meta-analysis. We searched PubMed, Embase, Google Scholar, and CNKI (China National Knowledge Infrastructure) databases for all related articles. The standardized mean difference and its 95% confidence interval was used to evaluate the association of leukemia with heavy metal(loid)s in serum. The statistical heterogeneity among studies was assessed with the Q-test and I 2 statistics. Among 4,119 articles related to metal(loid)s and leukemia, 21 studies met our inclusion criteria, which are all cross-sectional studies. These 21 studies involved 1,316 cases and 1,310 controls, based on which we evaluate the association of heavy metals/metalloids in serum with leukemia. Our results indicated positive differences for serum chromium, nickel, and mercury in leukemia patients, while a negative difference for serum manganese in acute lymphocytic leukemia (ALL). Our results suggested an elevated trend of serum chromium, nickel, and mercury concentrations in leukemia patients while descending trend of serum manganese concentration in ALL patients. The result of sensitivity analysis between lead, cadmium, and leukemia and publication bias of association between chromium and leukemia also needed attention. Future research work may focus on the dose-response relationship between any of these elements and the leukemia risks, and further elucidation of how these elements are related to leukemia may shed light on the prevention and treatment of leukemia. The online version contains supplementary material available at 10.1007/s40201-023-00853-2.


Bronchovascular mucormycosis: an urgent surgical problem.
The case of a 70-year-old male with lymphoblastic leukemia is reviewed, who presented the rare and almost always fatal complication of pulmonary mucormycosis, but who was treated satisfactorily with amphotericin B and surgery. The risk of massive hemoptysis in the course of mucormycosis that invades the lung vessels, makes us believe that surgery is an essential part of the management of this disease. It is suggested that the patient be operated as soon as the diagnosis is obtained, as we did in our case, to avoid other risks in combined management with amphotericin B.


Diversity of ethanolamine utilization by human commensal Escherichiacoli.
Ethanolamine (EA) is a substrate naturally present in the human gut and its catabolism by bacteria relies on the presence of eut genes encoding specific metabolic enzymes and accessory proteins. To date, EA utilization has been mostly investigated in gut bacterial pathogens. The aim of this study was to evaluate the ability of human gut commensal Escherichia coli isolates to utilize EA as a nitrogen and/or carbon sources. Although the capacity to consume EA is heterogeneous between the 40 strains of our collection, we determined that most of them could degrade EA to generate ammonia, a useful nitrogen resource for growth. Three isolates were also able to exploit EA as a carbon source. We also revealed that the inability of some strains to catabolize EA is explained either by mutations in the eut locus or by a defect in gene transcription. Finally, we demonstrated the importance of EA utilization for an optimal fitness of commensal E. coli in vivo. Our study provides new insights on the diversity of commensal E. coli strains to utilize EA as a nutrient in the gut and opens the way for new research in the field of interactions between host, gut microbiota and pathogens.


Use of botulinum toxin to treat blepharospasm in a 16-year-old with a dystonic syndrome.
A 16-year-old boy with generalized dystonia had continuous, severe blepharospasm and facial grimacing. Local intradermal injections of botulinum A toxin greatly reduced the spasms and improved function. No side effects were observed. Local botulinum A toxin injections may be useful in the treatment of eyelid and facial spasms in patients with generalized dystonias.


Inverted left atrial appendage bonded to atrial septum.
Inverted left atrial appendage (LAA) is a rare surgical complication. Our patient, a boy aged 2 years, was diagnosed with a partial atrioventricular defect with mild regurgitation of the left atrioventricular valve and a large primum atrial septal defect. Direct postoperative transesophageal echocardiography revealed a new left atrial mass attached to the atrial septum, without left ventricle inflow obstruction. Out of concern about the nature of this mass, we chose surgical direct examination. Intraoperatively, we diagnosed it as an inverted LAA accidentally attached to the atrial septum suture line. Awareness of this condition can avoid unnecessary diagnostic and therapeutic procedures.


Cold-passaged human parainfluenza type 3 viruses contain ts and non-ts mutations leading to attenuation in rhesus monkeys.
Cold-passaged (CP) mutants derived from the JS strain of wild type wt parainfluenza type 3 virus (PIV3) are being evaluated as candidate live virus vaccines. The wt virus was serially passaged 45 times at low temperature and mutant clones with the cold-adapted (CA), temperature-sensitive (ts), and attenuation (ATT) phenotypes were selected following passage levels 12, 18 and 45 (cp12, cp18, and cp45). The cp45 virus was more ts than the cp12 or cp18 mutants, although all 3 mutant viruses were clearly attenuated in rhesus monkeys compared to wild type virus. The mean peak titers of the cp12 and cp18 viruses administered by the intratracheal route were at least 6000-fold lower than JSwt in both the upper and lower respiratory tracts. The cp45 virus was not recovered from monkeys administered virus by the i.t. route alone; however, when the cp45 virus was administered by the intranasal route, it replicated in the upper respiratory tract to a level comparable to that of the cp12 and cp18 viruses, but continued to be markedly restricted in the lower respiratory tract. These data indicate that the cp12 and cp18 viruses contain predominantly non-ts attenuating mutations whereas the cp45 mutant has both non-ts and ts attenuating mutations. Each of the CP mutants induced a high level of resistance to wild type virus challenge. Also, the ATT phenotype of the cp12 and cp18 viruses as measured in rhesus monkeys was stable after replication in chimpanzees or humans, respectively, although the ts phenotype was not. Based on its greater level of temperature sensitivity in vitro and its greater degree of attenuation in rhesus monkeys, the cp45 virus appears to be the most promising vaccine candidate for humans.


Chemical usage in production agriculture: do crop insurance and off-farm work play a part?
In recent years a growing body of literature in the agricultural policy arena has examined the association between crop insurance and off-farm employment. However, little is known about the extent to which these two activities may be related to environmental quality, in particular their impacts on fertilizer/chemical use of the farm. To fill this gap, this paper examines the effect of crop insurance and off-farm work on fertilizer/chemical expenses within the farm household framework. Quantile regression results from a national representative farm-level data show that off-farm work by the farm operator tends to decrease fertilizer/chemical expenses, and the effect is more pronounced at the higher percentiles of the distribution of fertilizer/chemical expense. In contrast, a positive effect of crop insurance on fertilizer/chemical expenses is evident, and the effect is robust across the entire distribution.


E-selectin, resistin and reactive oxygen species levels in GnRH -agonist and -antagonist protocols in IVF/ICSI: a prospective cohort study.
To compare E-selectin, resistin and reactive oxygen species (ROS) levels in serum and follicular fluid (FF) of subfertile women undergoing Controlled Ovarian Hyperstimulation (COH) during IVF/ICSI cycles, using GnRH-agonist and -antagonist protocols. In this prospective cohort study, 85 subfertile women undergoing IVF/ICSI were included. Participants underwent the GnRH-agonist and -antagonist protocols; and blood samples were collected at three time points: basic (at start of COH), on the day of hCG and at oocyte retrieval (OR); and from the FF from the first follicle aspirate. Clinical and IVF cycle characteristics, were compared between groups, together with the levels of E-selectin, resistin and ROS in serum and FF, through ELISA. Their prognostic value on pregnancy outcomes was examined. Examining molecules levels are increasing in serum, from start of COH until OR, irrespectively of the protocol used; FF levels at OR were similar to those in serum at that day. Resistin FF levels were lower in GnRH agonists, compared with the antagonist protocol. Resistin levels at start of COH were associated with clinical pregnancy rates, and this remained significant following adjustment for age, BMI and IVF protocol used, while values of >13.5 ng/ml were associated with a six times greater odd of a pregnancy. E-selectin, resistin and ROS levels are increasing during COH, reaching their highest values at OR, with comparable values measured in the FF at that time. Resistin values >13.5 ng/ml are linked with a 6-fold increase on the odds of a pregnancy.


A retrospective and tridimensional study of the maxillary sinus in patients with cleft lip and palate.
Structural or anatomic differences may arise during the development of the maxillary sinus and the process of fusion of the palate in the presence of cleft lip and palate. The present study aimed to compare the maxillary sinus volume of patients with unilateral cleft lip and palate and a control group (noncleft patients). In this retrospective case-control study, 160 cone-beam computed tomography images of 80 unilateral cleft lip and palate patients (41 males and 39 females; mean age, 12.7 ± 6.03 years) and 80 control patients (43 males and 37 females; mean age, 13.1 ± 6.27 years) were evaluated through the ITK-SNAP software (Cognitica, Philadelphia, Pa) to access the maxillary sinus volume. Analysis of covariance and regression analysis were used to assess the differences between the groups while considering the relationship between maxillary sinus volume, age, and sex. No statistically significant differences were found in the maxillary sinus volume analyzing a unilateral cleft lip and palate and a control group (P = 0.677). Considering the cleft group, there is a tendency for the maxillary sinus volume of the cleft side to be smaller than its contralateral (P < 0.001). Statistically significant differences were found in the maxillary sinus volume, regarding the age and sex of cleft and noncleft patients (P < 0.001 for age; P = 0.001 for sex). According to these results, the presence of unilateral cleft lip and palate did not affect the maxillary sinus volume, comparing cleft and noncleft patients. A biphasic growth pattern of the maxillary sinus and a presence of sexual dimorphism were found.


Ultrasonic impregnation of MnO2/CeO2 and its application in catalytic sono-degradation of methyl orange.
MnO2/CeO2 catalyst was prepared by ultrasonic impregnation method. The traditional and stirring impregnation methods were used as control. Results showed that ultrasonic impregnation was the best synthesis method. The impregnation time was shortened from 120 min (traditional method) to 20 min, the specific surface area of catalyst was three times larger, and the catalytic activity of catalyst was also the highest. Furthermore, MnO2 had crystalline structure and distributed uniformly on the support, CeO2. The preparing conditions were further examined and the optimal conditions were found to be: 20 min of ultrasonic impregnation, 4.3 mol/L of manganese nitrate concentration and 450 °C of calcination temperature. The so prepared catalyst removed 94% of methyl orange in 30 min with a dosage of 0.5 g/L. The efficiency was 77.7% and 85.9% for traditional and stirring impregnation method under the same experimental conditions. The reaction process involved two stages: adsorption-dominated and degradation-dominated stages. The reaction rate constant of adsorption-dominated stage had little difference. However, compared with traditional impregnation, the reaction rate constant of degradation-dominated stage improved from 0.01 to 0.14 min-1 by ultrasonic impregnation. Mechanism analysis showed that the activity of ultrasonic impregnation MnO2/CeO2 was improved by the effects of acoustic cavitation and ultrasound oscillation on solid-liquid transport and distribution status.


Advances in the detection of β-lactamase: A review.
β-lactamase, an enzyme secreted by bacteria, is the main resistant mechanism of Gram-negative bacteria to β-lactam antibiotics. The resistance of bacteria to β-lactam antibiotics can be evaluated by testing the activity of β-lactamase. Traditional phenotypic detection is a golden principle, but it is time-consuming. In recent years, many new methods have emerged, which improve the efficiency by virtue of their sensitivity, low cost, easy operation, and other advantages. In this paper, we systematically review these researches and emphasize their limits of detection, sample operation, and test duration. Noteworthily, some detection systems can identify the β-lactamase subtype conveniently. We mainly divide these tests into three categories to elaborate their characteristics and application status. Both advantages and disadvantages of these methods are discussed. Additionally, we analyze the recent 5 years published researches to predict the trend of development in this field.


Perceptual, Aerodynamic and Acoustic Evaluation of Vocal Characteristics in Subjects With Obesity.
Obesity has tripled since 1975 and affects health across many domains. Increasing body mass index increases the risk to the obese subject of many non-communicable diseases. The study evaluated the perceptive, aerodynamic, and acoustic parameters that characterize the voice of the obese population. Eighty adult subjects (40 participants in each obese and control group) aged 18-50 years were enrolled. The perceptual voice analysis was performed using the Consensus Auditory Perceptual Evaluation of Voice. The aerodynamic and acoustic voice analyses were performed using the MIR Spiro lab instrument and Doctor's Speech software. A digital stopwatch was also used to measure maximum phonation time. Statistical analysis revealed a significant difference (P-value <0.05 and t value >2) between two groups on acoustic parameters, specifically Normalized noise energy and fundamental frequency tremor (F0 tremor). Normalized noise energy and fundamental frequency tremor were greater in the obese group. Moreover, maximum phonation time and expiratory reserve volume were significantly reduced in the obese group. Results of the present study showed poor voice quality and reduced expiratory reserve volume in obese individuals. This could be credited to the adverse effects of accrued adipose on the functioning of the laryngeal and respiratory systems. Increasing body mass index escalates the risk to the obese subjects of many non-communicable diseases.


Mixed-chain phosphatidylcholine analogues modified in the choline moiety: preparation of isomerically pure phospholipids with bulky head groups and one acyl chain twice as long as the other.
Diacylphosphatidylcholines were synthesized with widely different acyl chain lengths and bulky head groups. Lysophosphatidylcholine was acylated at room temperature within 6 h with a 10-fold molar excess of fatty acid anhydride in dry, alcohol-free chloroform in the presence of 1.2 equivalents of 4-pyrrolidinopyridine as a catalyst, affording the mixed-acid phosphatidylcholines with widely different chain lengths in more than 90% yield and with less than 1% acyl migration. The syntheses of isomerically pure 1-stearoyl-2-decanoyl- and 1-stearoyl-2-undecenoyl(delta 10)-sn-glycero-3-phosphocholines C(18:0)/C(10:0)-PC and C(18:0)/C(11:1 delta 10)-PC, respectively), followed by conversion to various head-group analogues, are illustrated here. The transition peak widths at half-height of the endotherms obtained by differential scanning calorimetry are consistent with very high isomeric purity. Phospholipase D from Streptomyces chromofuscus was used as a catalyst in the hydrolysis of C(18:0)/C(10:0-PC to give the corresponding phosphatidic acid in quantitative yield. The latter compound was condensed with 10 molar equivalents of various N,N,N-trialkylammonium alkanols (as their p-toluenesulfonate or tetraphenylborate salt) in the presence of trichloroacetonitrile in dry pyridine under nitrogen atmosphere to yield the C(18:0)/C(10:0) phospholipids bearing modified head groups, which were purified by flash chromatography.


Adenoviral-vector mediated transfer of HBV-targeted ribonuclease can inhibit HBV replication in vivo.
Hepatitis B virus (HBV)-targeted ribonuclease (HBV-TR) is a fused protein of HBV core protein and a ribonuclease, human eosinophil-derived neurotoxin (hEDN). Our previous results showed that HBV-TR could effectively inhibit HBV replication in vitro. To test whether HBV-TR can inhibit HBV replication in vivo, we constructed a recombinant adenoviral vector expressing HBV-TR (Ad-TR) and used it to treat HBV-transgenic mice. Immunohistochemical staining showed that TR was expressed at varied levels in different tissues of Ad-TR-treated mice. Serum HBsAg concentration was decreased by 64.8% for the Ad-TR-treated mice compared with empty adenoviral vector-treated control mice. The amount of HBV-DNA in the livers of the Ad-TR-treated mice was 0.74 x 10(7) copies/mug of genomic DNA while the amount of HBV-DNA in the livers of the empty adenoviral vector-treated control mice was 2.86 x 10(7) copies/mug of genomic DNA. Serum HBV-DNA of Ad-TR-treated mice was also decreased by 71.4% compared with empty adenoviral vector-treated control mice. In addition, for some Ad-TR-treated mice, the expression of HBsAg in the liver cells turned negative. No discernible adverse effects were observed for Ad-TR-treated mice. Taken together, our results indicated that adenovirus mediated transfer of HBV-TR can inhibit HBV replication in vivo.


IKKβ primes inflammasome formation by recruiting NLRP3 to the trans-Golgi network.
The NLRP3 inflammasome plays a central role in antimicrobial defense as well as in the context of sterile inflammatory conditions. NLRP3 activity is governed by two independent signals: the first signal primes NLRP3, rendering it responsive to the second signal, which then triggers inflammasome formation. Our understanding of how NLRP3 priming contributes to inflammasome activation remains limited. Here, we show that IKKβ, a kinase activated during priming, induces recruitment of NLRP3 to phosphatidylinositol-4-phosphate (PI4P), a phospholipid enriched on the trans-Golgi network. NEK7, a mitotic spindle kinase that had previously been thought to be indispensable for NLRP3 activation, was redundant for inflammasome formation when IKKβ recruited NLRP3 to PI4P. Studying iPSC-derived human macrophages revealed that the IKKβ-mediated NEK7-independent pathway constitutes the predominant NLRP3 priming mechanism in human myeloid cells. Our results suggest that PI4P binding represents a primed state into which NLRP3 is brought by IKKβ activity.


[Compound odontoma with history of trauma: report of a case].
Clinical and roentgenographical features are described for a compound odontoma in a ten-year old male with a history of trauma in the anterior region of the face. Diagnostical methods and surgical handling are discussed, with a review of the pertinent literature.


Immune system associated antigens expressed by cells of the human central nervous system.
HLA-DR, HLA-DQ and HLA-DP are class II major histocompatibility complex (MHC) antigens necessary for T cell binding and antigen presentation. Interleukin-2 is a lymphokine used by the immune system to signal proliferation of cells in the immune response. Using unfixed tissue and free-floating immunohistochemistry, we show profuse immunoreactivity for these immune antigens in white and gray matter samples from normal and Alzheimer's (AD) disease patients. On morphologic grounds, immunoreactive cell types appear to include astrocytes, microglia, macrophages, and endothelial cells or pericytes.


Keratinocytes and dermal factors activate CRABP-I in melanocytes.
Recognition that cellular retinoic acid binding protein (CRABP)-I and CRABP-II are found in different cell types has provided additional support for the presumably divergent roles of these two proteins in mediating retinoic acid (RA) effects in human skin. CRABP-II is expressed in fibroblasts and keratinocytes, and CRABP-I in as yet unidentified cells, possibly epidermal melanocytes. Recently, we demonstrated that each of these RA-binding proteins in human skin possesses two classes of binding sites, possibly related to the state of phosphorylation of the proteins. We now characterize the cutaneous origin of CRABP-I further using an anion-exchange HPLC assay that allows effective separation of the two proteins in human skin, and a fluorescent in situ hybridization technique. We report that CRABP-I is expressed in isolated melanocytes at the mRNA level, although under these circumstances the protein has minimal RA-binding activity, and that keratinocytic and dermal influences are required for CRABP-I activity in melanocytes. This melanocyte origin for CRABP-I and the improvement by RA of the irregular hyperpigmentation associated with photoaging led us to examine the effects of RA using various cellular associations, from conventional pure cultures of melanocytes grown on plastic dishes to a pigmented skin equivalent consisting of melanocytes and keratinocytes grown on a dermal equivalent. We established that the inhibitory effects of RA on melanogenesis do not result from a direct effect on melanocytes alone but also involve keratinocytes and dermal influence. These data expand our understanding of cell-to-cell signaling in cutaneous pigmentation, and strongly suggest a role for CRABP-I in mediating RA effects on melanogenesis.


Specific bone-protective effects of metabolites/derivatives of tamoxifen and clomiphene in ovariectomized rats.
In the ovariectomized (ovx) rat, the nonsteroidal antiestrogens, clomiphene (CLO) and tamoxifen (TAM), at dose levels that prevent development of osteopenia to a degree approaching that of 17beta-estradiol are, in contrast to 17beta-estradiol, only weakly uterotrophic. Metabolites of CLO and TAM might contribute differentially to these effects. Thus, we have evaluated bone protective and uterine effects in ovx rats of two such metabolites: 4-hydroxy CLO, produced by p-hydroxylation of CLO; and 4HTA, produced from TAM by stepwise replacement of its dimethylaminoethyl side chain with an acetic acid moiety, accompanied by p-hydroxylation. Also reported are effects of D4HTA, the dihydrodesethyl derivative of 4HTA previously characterized as a full estrogen mimetic in vitro. Administration of 4-hydroxy CLO (2.5 mg/kg subcutaneously) 5 days/week for 5 weeks to 3-month-old ovx rats resulted in complete prevention of bone loss and suppression of bone turnover to levels comparable to those of intact controls and to those of ovx animals similarly receiving 17beta-estradiol (10 microg/kg). However, uterine weight in animals receiving 4-hydroxy CLO was 64% less than that in 17beta-estradiol-treated animals. Although 4HTA (3.7 mg/kg s.c.) had a modest uterotrophic effect, it did not prevent bone loss associated with ovariectomy. In contrast, D4HTA (3.6 mg/kg s.c.) partially reduced bone turnover indicators and cancellous bone loss in a manner similar in many ways to that observed in TAM-treated ovx animals, but it had no uterotrophic effect. These results suggest that, although 4HTA does not contribute to the bone-protective effect of TAM, 4-hydroxy CLO might augment that of CLO.


Identification, characterization, and agglutinating activity of a novel C-type lectin domain family 3 member B (CLEC3B) discovered in golden pompano, Trachinotus ovatus.
The lectins are a large family of carbohydrate-binding proteins that play important roles in the innate immune response of various organisms. Although C-type lectin domain family 3 member B (CLEC3B), an important member of C-type lectin, has been well documented in humans and several other higher vertebrates, little is currently known about this molecule in economically important marine fish species. In this study, through transcriptomic and BLAST screening, a novel CLEC3B gene was identified in the golden pompano (Trachinotus ovatus). The T. ovatus CLEC3B (ToCLEC3B) was subsequently characterized by bioinformatic analysis and compared with those reported in other species. In addition, the expression patterns of ToCLEC3B in different tissues under normal condition and at different times post pathogen challenge were assessed. Furthermore, the agglutinating activity of ToCLEC3B with and without Ca2+ against different bacteria and blood cells of donor species were verified using the recombinant T. ovatus CLEC3B (rToCLEC3B). Our results demonstrated that ToCLEC3B is a Ca2+-dependent galactose-binding lectin with a single copy of carbohydrate recognition domain (CRD). Similar to CLEC3B reported in other species, the CRD domain of ToCLEC3B consists of two α-helices, six β-sheets, and four loops, forming two Ca2+- and a galactose-binding sites. According to the phylogenetic analysis, the ToCLEC3B was highly similar (similarity at 95.00%) to that of its relative, the greater amberjack (Seriola dumerili). The expression of ToCLEC3B was detected in all tissues examined under normal condition and was significantly up-regulated by injection of pathogenic microbes. In addition, the rToCLEC3B exhibited strong agglutinating activity against different bacteria and blood cells of donor species in the presence of Ca2+. Our results indicate that ToCLEC3B is a constitutive and inducible acute-phase immune factor in the host's innate immune response of T. ovatus.


Expression of cyclin D1 and retinoblastoma protein in colorectal cancer.
Abnormal expression of the retinoblastoma protein (pRb) and cyclin D1 have been reported in a variety of malignancies, but the frequencies of these deregulations and their relation to prognosis in colorectal cancer has not been clarified. We characterised 90 colorectal cancers with respect to immunohistochemical expression of cyclin D1, pRb and Ki-67. Two of 90 (2%) tumours lacked nuclear pRb staining, indicating inactivation of the protein, while 10 (11%) expressed high levels of pRb. Abnormal expression of pRb was significantly correlated to low levels of nuclear cyclin D1 observed in 32% of the tumours. Strong nuclear cyclin D1 expression was detected in 12% of the tumours. Cytoplasmic staining of cyclin D1 was observed in 17% of the tumours, showing an inverse relationship (P = 0.006) to the Ki-67 labelling index. Eight of 11 tumours with high nuclear overexpression of cyclin D1 and both tumours with pRb defects were located in the right colon in comparison with zero of 25 in the rectum (P = 0.009). Regarding prognosis, neither pRb nor cyclin D1 expression correlated with patient survival.


[Resistance studies: when are they indicated?].
Cytomegalovirus (CMV) resistance to antiviral drugs is an emerging problem and is due to selection of mutations in the viral genome. Although ganciclovir resistance is the most common and widely studied, there is resistance to all antiviral agents. Risk factors for the development of resistance are the absence of preexisting immunity to CMV, lung and pancreas transplantation, high viral loads, intense concomitant immunosuppressive therapy and prolonged exposure to ganciclovir or suboptimal levels of this drug. Antiviral resistance should be suspected when, despite adequate treatment exposure for 2 weeks, an increase in viral load, or persistence or clinical progression of CMV disease are detected. However, failure to respond cannot always be attributed to antiviral resistance nor does resistance always lead to poor clinical outcome. When resistance is suspected, phenotypic and genotypic confirmation is required. The most common mutations are those in the UL97 gene, which confers ganciclovir resistance. However, foscarnet and cidofovir can be used. The UL54 mutation is not uncommon, whether alone or in combination with UL97 mutations. The combination of UL54 and UL97 mutations is associated with high-grade and multiple resistance. Early detection of resistance is essential to prevent unfavorable outcome and the development of multi-drug resistance. In patients with a slow response to treatment and without mutations associated with resistance, plasma ganciclovir levels and specific CMV immunity should be investigated.


Evaluation of effectiveness of safety seatbelt legislation in the United Arab Emirates.
Seatbelt legalisation was implemented in the United Arab Emirates (UAE) in January 1999. This provided the opportunity to evaluate the effectiveness of the legislation in the Eastern District of Abu Dhabi Emirate in the UAE by establishing levels of injury severity from motor vehicle crashes (MVC) before and after the legislation and the rate of compliance with the legislation. Data were obtained from a major hospital in the Eastern District of Abu Dhabi Emirate, UAE. Subjects were a systematic sample of MVC victims who arrived alive at hospital in either the pre-implementation period (January-June 1998) or the post-implementation period (February-August 2000). The main measures of outcome were injury severity codes, numbers of hospital bed days and rates of admission and discharge at hospital. The analysis of injury severity from MVCs, from the pre- to the post-implementation period, revealed a significant declining trend (chi-square = 77.68, P < 0.001). While the proportion of minor injuries increased from 42% (95% CI: 36-48%) in the pre-implementation period to 77% (95% CI: 71-83%) in the post-implementation period, the proportion of "moderate to fatal injuries" declined from 54% (95% CI: 48-60%) to 17% (P = 0.001) and the median number of hospital bed days declined from 5 days (25% = 2; 75% = 8 ) to 3 days (25% = 1; 75% = 4 ). The rate of seatbelt compliance reported by occupants involved in MVCs in the post-implementation period was 59% (95% CI: 52-67%). The implementation of the seatbelt legislation in the Eastern District of Abu Dhabi Emirate was associated with statistically significant reduction in morbidity in those arriving alive at hospital following MVC, including reduced severity of injury, admission rate to hospital and the duration of hospital stay. More active implementation of seatbelt law would most likely further reduce severity of MVC injuries and fatalities in the Eastern District of Abu Dhabi Emirate, UAE.


Pharmacology and pharmacokinetics of drugs used to treat cardiac disease in horses.
The rational therapy of cardiovascular disease in horses requires a thorough knowledge of the pharmacology and pharmacokinetics of several specific drugs (digitalis, digoxin). Calcium solutions, dopamine, and dobutamine are frequently used to treat congestive heart failure in horses. Quinidine, procainamide, lidocaine, and propranolol are used to treat a variety of supraventricular and ventricular arrhythmias. Furosemide, a highly potent loop diuretic, is used to eliminate edema and promote diuresis. A thorough understanding of the applied pharmacology, dosage recommendations, toxicity, and practical considerations must be attained before these drugs can be used effectively.


Analysis of genetic factors associated with fatty liver disease-related hepatocellular carcinoma.
Single-nucleotide polymorphisms (SNPs) in PNPLA3 and hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) genes are associated with fatty liver disease (FLD) progression and carcinogenesis. In the present study, we evaluated the characteristics of Japanese FLD patients according to HSD17B13 polymorphisms. We enrolled 402 patients who were clinically and pathologically diagnosed with FLD (alcoholic: 63 cases, nonalcoholic: 339 cases) at our hospital in 1990-2018 (228 males; median age: 54.9 [14.6-83.6] years). FLD patients with HSD17B13 A/A (212 cases) and others (A/AA or AA/AA; 190 cases) were compared. Compared to patients with HSD17B13 A/A and others, those with the A/A genotype showed increased incidence of hepatocellular carcinoma (HCC) (A/A vs. others; 18.4% vs. 9.5%, p = 0.01), cardiovascular diseases (14.2% vs. 4.2%, p < 0.01), and hypertension (56.6% vs. 47.4%, p = 0.06). In patients without A/A, the HCC incidence was significantly reduced in those with alcohol-related FLD, fibrosis-4 index <2.67, and the PNPLA3 CC genotype; however, there was no significant difference in nonalcoholic-FLD. Patients without HSD17B13 A/A showed severe steatosis (77% vs. 88.6%, p < 0.01). New HCC developed in 11 cases and the 5-year incidence rate of HCC was 3.3% in patients with both PNPLA3 GG/GC and HSD17B13 A/A, which was significantly higher than the rate for those with other SNP profiles (0.6%, p = 0.03). Inhibiting HSD17B13 activity may prevent HCC development, particularly in alcohol-related FLD and low-risk patients. Therefore, combinations of SNPs and other risk factors can be used for screening FLD-HCC.


Sialic acid dependent cell adhesion to collagen IV correlates with in vivo tumorigenicity of the human colon carcinoma sublines HCT116, HCT116a and HCT116b.
Cell surface sialylation of three metastasizing sublines HCT116, HCT116a and HCT116b of a human colon carcinoma was shown to correlate with their in vivo tumorigenicity. Lectin binding studies revealed further differences in cell surface glycosylation between HCT116a and HCT116 sublines. Binding to collagen IV correlated with the in vivo aggressiveness of the cells, whereas binding to fibronectin did not. On a laminin substrate the most tumorigenic line adhered best, but binding of the other lines was similar. Sialidase treatment of the cells had no effect on cell binding to laminin and fibronectin, but resulted in a decrease of cell binding to collagen IV.


The effects of gabapentin in the rat hippocampus are mimicked by two structural analogs, but not by nimodipine.
Gabapentin has been shown to reduce paired-pulse inhibition in the dentate gyrus of the urethane-anesthetized rat and has been shown to block calcium channels, but its not known how these possible mechanisms relate to its antiepileptic effect. Here, we tested two structural analogs of gabapentin for the ability to reduce seizure duration and to alter paired-pulse inhibition in the dentate gyrus in urethane anesthetized adult Sprague-Dawley rats. We compared with our results to those with diazepam, an anxiolytic and GABA(A) positive modulator and with nimodipine, a specific blocker of L-type Ca2+ channels. Both structural analogs of gabapentin caused a dose-dependent loss of paired-pulse inhibition and blocked the lengthening of the duration of the seizure discharge. Nimodipine also blocked the increase in duration of the seizure discharge, but increased paired-pulse inhibition. The effects of the GABA derivatives on paired-pulse inhibition and on seizure duration may have a common mechanism. Furthermore, our results indicate that gabapentin's postulated block of L-type calcium channels is not responsible for reducing paired-pulse inhibition. However, calcium channel block could still be the basis for the antiepileptic effect of gabapentin and its analogs.


The promotive effects of thymosin beta4 on neuronal survival and neurite outgrowth by upregulating L1 expression.
Thymosin beta(4) (Tbeta4) is a major actin-sequestering peptide widely distributed in mammalian tissues including the nervous system. The presence of this peptide in the nervous system likely plays a role in synaptogensis, axon growth, cell migration, and plastic changes in dendritic spine. However, the effects of Tbeta4 on the survival of neurons and axonal outgrowth have still not been fully understood. So far it is not clear if the effects of Tbeta4 are associated with L1 functions. In the present study, we hypothesized that Tbeta4-induced up-regulation of L1 synthesis could be involved in the survival and axon outgrowth of cultured spinal cord neurons. To test this hypothesis, primarily cultured neurons were prepared from the mouse spinal cord and treated with various concentrations of Tbeta4 ranging from 0.1 to 10 microg/ml. The analysis of L1 mRNA expression and protein synthesis in neurons was then carried out using RT-PCR and western blot assays, respectively. After the addition of Tbeta4 to cultures, cells were then treated with antibodies against distinct domains of L1-Fc. Subsequently, beta-tubulin III and L1 double-labeled indirect immunofluorescence was carried out. Meanwhile, L1 immunofluorescent reactivity was analyzed and compared in cells treated with Tbeta4. Furthermore, the number of beta-tubulin III-positive cells and neurite lengths were measured. We found that Tbeta4 enhanced L1 expression in a dose-dependent manner, and the highest L1 mRNA and protein synthesis in cells increased by more than 2.1- and 2.3-fold in the presence of Tbeta4 at identical concentrations, respectively. Moreover, it also dose dependently enhanced neurite outgrowth and neuronal survival. Compared to conditions without Tbeta4, the length of neurite and neuronal survival increased markedly in presence of 0.5, 1, and 5 microg/ml Tbeta4, respectively, whereas the effects of Tbeta4 were significantly attenuated or inhibited in the process of L1-Fc antibodies treatment. These above results indicate that the promotive effect of Tbeta4 on the survival and neurite outgrowth of cultured spinal cord neurons might be mediated, at least in part via a stimulation of the production of L1 in the neurons.


Longitudinal change in microRNA-130a expression and its correlation with the risk of developing major adverse cardiovascular and cerebral events in patients undergoing continuous ambulatory peritoneal dialysis.
MicroRNA-130a (miR-130a) regulates angio-cellular dysregulation, atherosclerosis, and cardiocerebral injuries, serving as a biomarker for major adverse cardiovascular and cerebral events (MACCE) in several chronic diseases. However, its clinical application in patients with end-stage renal disease (ESRD) undergoing continuous ambulatory peritoneal dialysis (CAPD), who are at a high risk of developing MACCE, has not been reported. Therefore, this study aimed to explore this aspect. miR-130a expression in peripheral blood mononuclear cells obtained from 50 healthy controls (HCs) at recruitment and 257 ESRD patients undergoing CAPD at month (M)0, M12, M24, and M36 was determined by reverse transcription-quantitative polymerase chain reaction. ESRD patients undergoing CAPD were followed up until MACCE occurred or M36. Then, MACCE were recorded, and MACCE-free survival was calculated. miR-130a expression was significantly lower in ESRD patients undergoing CAPD than in HCs (p < 0.001). In addition, miR-130a expression significantly decreased from M0 to M36 in ESRD patients undergoing CAPD (p < 0.001). Moreover, miR-130a expression at M0, M12, and M24 was significantly lower in patients with MACCE than in those without MACCE (all p < 0.05). Furthermore, high miR-130a expression at M0, M12, and M36 was significantly correlated with prolonged MACCE-free survival in ESRD patients undergoing CAPD (all p < 0.05), and high miR-130a expression at M0 was an independent factor for improved MACCE-free survival (p = 0.015; hazard ratio (HR) (95% confidential interval): 0.456 (0.243-0.857)). miR-130a expression decreases continuously with disease progression in patients with ESRD undergoing CAPD. Additionally, this expression is negatively correlated with MACCE risk in these patients.


Monoclonal antibodies which differentiate high- and low-affinity binding sites of interleukin-2.
Five monoclonal antibodies (L15, L20, L23, L34, and L61) against human recombinant interleukin-2 were tested for their effects on the interleukin-2 bioactivity and binding. Four of these monoclonal antibodies, L15, L20, L34, and L61, which had neutralizing activity, completely blocked interleukin-2 binding to the high-affinity receptor. On the other hand, L23, which had a very weak neutralizing activity, blocked interleukin-2 binding to the low-affinity receptor. These results suggest that there are at least two distinct binding sites on the interleukin-2 molecule; those for the high-affinity receptor and those for the low-affinity receptor. These monoclonal antibodies should be useful tools in the study of the interaction between interleukin-2 and interleukin-2 receptor.


The effect of pre-admission education on domiciliary recovery following laparoscopic cholecystectomy.
The objectives of this randomised controlled study were to determine if pre-admission patient education affects post-operative pain levels, domiciliary self-care capacity and patient recall following a laparoscopic cholecystectomy (LC). Participants were randomised to receive the standard preadmission program (SP) or an individualised, education intervention (El). A pre-operative questionnaire was administered in the pre-admission clinic to determine participants' knowledge of LC and post-operative management. Telephone follow-up and post-operative questionnaire were conducted approximately 14 days post discharge. Preadmission clinic of a Sydney, Australia, tertiary referral hospital. Ninety-three elective LC patients. EI participants experienced lower pain levels and had significantly greater recall of provided information. However, no significant differences were found between the control and intervention groups for domiciliary self-care. Pre-admission education intervention helps reduce post-operative pain levels following LC and significantly increases patients' knowledge of self-care and complication management.


Therapy of early breast cancer: preliminary results of the German Breast Cancer Study.
The German Breast Cancer Study Group has a large, homogeneous patient population with pT1 pN0 breast cancers who have undergone a detailed pathohistological work-up and uniform treatment. Seventy institutions take part in this study, mostly community hospitals. All pathologic specimens are reviewed by the Pathology Reference Center. Moreover, in order to improve the quality of radiation therapy, all dosimetric data, radiation protocols, and localization, and verification films are reviewed by the Radiotherapeutic Study Centre. By January 31, 1988, 762 patients had been recruited. At the moment, after an admittedly short follow-up period for the majority of our patients, there is no evidence of differences between the two treatment arms concerning the incidence of local and distant recurrences, contralateral breast cancers, and other malignancies. However, the study demonstrates several unresolved problems, mainly the collection of follow-up data which can arise when many institutions especially community hospitals and general practitioners, are involved in a prospective trial.


Regulation of prostaglandin production by osteoblast-rich calvarial cells.
The effect of various factors upon prostaglandin (PG) production by the osteoblast was examined using osteoblast-rich populations of cells prepared from newborn rat calvaria. Bradykinin and serum, and to a lesser extent, thrombin, were all shown to stimulate PGE2 and 6-keto-PGF1 alpha (the hydration product of PGI2) secretion by the osteoblastic cells. Several inhibitors of prostanoid synthesis, dexamethasone, indomethacin, dazoxiben and nafazatrom, were tested for their effects on the calvarial cells. All inhibited PGE2 and PGI2 (the major arachidonic acid metabolites of these cells) production with half-maximal inhibition by all four substances occurring at approximately 10(-7) M. For dazoxiben and nafazatrom, this was in contrast to published results from experiments in vivo which have indicated that the compounds stimulated PGI2 production. Finally, since the osteoblast is responsive to bone-resorbing hormones, these were tested. Only epidermal growth factor (EGF) was shown to modify PG production. At early times EGF stimulated PGE2 release, however, the predominant effect of the growth factor was an inhibition of both PGE2 and PGI2 production by the osteoblastic cells. The present results suggest that the bone-resorbing hormones do not act to cause an increase in PG by the osteoblast and that any increase in PG production by these cells may be in response to vascular agents.


An Unprecedented Bird Nest Molybdenum(V) Cobalto-Phosphate Nanosized Wheel Constructed from the [H55 (Mo24 O48 )(Co4 O)2 Co16 (PO4 )42 (py)6 (EtOH)2 (H2 O)11 ]3- Anion.
An unprecedented bird-nest high-nuclear molybdenum(V) cobalto-phosphate nanosized wheel modified by imidazole (im) and pyridine (py), {[H55 (Mo24 O48 )(Co4 O)2 Co16 (PO4 )42 (py)6 (EtOH)2 (H2 O)11 ]- @[(Him)2 (Hpy)]}(N-Et-py)(H2 PO4 )(py)7 (EtOH)⋅12 H2 O (1), has been successfully synthesized by self-assembly. The anionic huge wheel consists of two rare {Co4 O} squares, four {Co4 } tetramers, four {Mo4 } tetramers and four {Mo2 } dimers, linked by bridging oxygen atoms and [PO4 ] groups and encloses two imidazolium cations and a protonated pyridium for charge balance. Surprisingly, 1 represents the first twisted wheel-shaped cluster with a record high-nuclear molybdenum(V) cobalto-phosphate. The delocalized electron effects of the cluster are enhanced with the help of coordinated py ligands, which endows 1 with an excellent third-order nonlinear optical (NLO) response. Additionally, 1 also shows a better photocatalytic water oxidation activity than Co(NO3 )2 with the O2 production of 205 μmol during 6 h in the absence of the [Ru(bpy)3 ]2+ photosensitizer.


Regeneration, health status and quality of life after rhG-CSF-stimulated stem cell collection in healthy donors: a cross-sectional study.
Mobilized allogeneic PBPC are increasingly used instead of BM for allogeneic stem cell grafting. Although the short-term safety profile of recombinant human (rh)G-CSF seems acceptable, only minimal data on long-term safety are available. We therefore reviewed data on 171 sibling donors (M/F: 98/73) with respect to side effects of rhG-CSF and PBPC collection and impact on quality of life (QoL) and health status. In a cross-sectional study, we investigated the actual QoL and health status of the donors as well as the need for medical treatment since PBPC donation by a questionnaire that was sent to 151 donors. Ninety-five (64%) of the addressed donors responded to the questionnaire, but only 69 (46%) of them reported on their actual health status and QoL, which was good to very good in the majority of them. Two donors developed malignancies in the post-donation course. In general, PBPC collection after rhG-CSF mobilization was well tolerated by the responding donors. Although the reported events in medical history after PBPC donation do not seem to be associated with rhG-CSF administration or the collection procedure, a lifelong follow-up of donors should be obligatory.


Synthesis of 2,3-disubstituted indole using palladium(II)-catalyzed cyclization with alkenylation reaction.
The reaction of ethyl 2-ethynylphenylcarbamate derivative with alkenes in the presence of a palladium(II) catalyst, copper dichloride and tetrabutylammonium fluoride (TBAF) produced 2-substituted 3-ethenylindoles during refluxing. The intramolecular cyclization reaction of ethyl 2-ethynylphenylcarbamates, which have an ethenyl part in the ethynyl group, was also used to produce carbazole derivatives.


[Successful bone marrow transplantation with a matched unrelated donor in an acute promyelocytic leukemia patient after reinduction therapy with arsenic trioxide].
A 44-year-old man with relapsed acute promyelocytic leukemia (APL), refractory to all-trans-retinoic acid (ATRA), daunorubicin, and cytosine arabinoside, was treated with arsenic trioxide (ATO). ATO was given intravenously at a dose of 0.15 mg/kg/day for 20 days, and the patient achieved complete remission. No serious adverse events related to ATO infusion were observed. He received ATO for 10 days as consolidation therapy and subsequently underwent HLA-matched unrelated donor stem cell transplantation. He remains in molecular remission 10 months after transplant. This case suggests that ATO could be a useful therapy prior to allogeneic stem cell transplantation in relapsed APL.


Unraveling the mysteries of classical preconditioning.
Nearly two decades have passed since the first report about ischemic preconditioning. Although we do not yet know unequivocally what the final effector is, we have learned a lot about the signal transduction pathways that result in protection, and have some good prospects for the final step that results in survival or necrosis of the ischemic myocardium. Many investigators have contributed to our current knowledge. We were heartened to learn that four of our JMCC publications are included in the 20 top-cited papers in the journal's history. It is gratifying that our prior publications have generated some interest and stimulated important debate as documented by the high number of citations by scientists in the bibliographies of their own papers. In this document, we have been asked to reflect on those four papers and comment on where they have led us.


Analysis of cause of failure of new targeting peptide in PEGylated liposome: molecular modeling as rational design tool for nanomedicine.
Drug nanocarriers are often derivatized with targeting moieties to achieve site specific delivery, however, the results from this approach have, as yet, not reached expectations. We have tested a new phage display based targeting moiety, the activated endothelium targeting peptide (AETP), for its vascular endothelium directed targeting efficiency, when anchored to a PEGylated liposome via maleimide chemistry. Our results have, however, not shown any evidence of improved targeting. We have hypothesized that the failure of the AETP moiety is due to its availability to target receptors being restricted, as a result of steric hindrance due to the PEG polymer, and possibly affinity for bloodstream proteins, particularly human serum albumin (HSA). In this context, molecular modeling was used to contrast the properties of the AETP moiety to those of the RGD targeting peptide, already found to be effective in previous trials. Our molecular dynamics simulation results indicate the AETP moiety is located within the PEG layer, and its hydrophobic nature causes it to be obscured by PEG to a greater extent than the more hydrophilic RGD targeting peptide. Protein-ligand docking results indicated similar affinities for HSA of both the AETP moiety and a PEG fragment, and a significantly lower affinity for the RGD peptide. We know of no means to investigate this experimentally with atomic level resolution, thus our use of computational methods to investigate this can be seen as a new tool for rational design in nanomedicine.


Expanding the paradigm of thiol redox in the thermophilic root of life.
The current paradigm of intracellular redox chemistry maintains that cells establish a reducing environment maintained by a pool of small molecule and protein thiol to protect against oxidative damage. This strategy is conserved in mesophilic organisms from all domains of life, but has been confounded in thermophilic organisms where evidence suggests that intracellular proteins have abundant disulfides. Chemical labeling and 2-dimensional gel electrophoresis were used to capture disulfide bonding in the proteome of the model thermophile Sulfolobus solfataricus. The redox poise of the metabolome was characterized using both chemical labeling and untargeted liquid chromatography mass spectrometry. Gene annotation was undertaken using support vector machine based pattern recognition. Proteomic analysis indicated the intracellular protein thiol of S. solfataricus was primarily in the disulfide form. Metabolic characterization revealed a lack of reduced small molecule thiol. Glutathione was found primarily in the oxidized state (GSSG), at relatively low concentration. Combined with genetic analysis, this evidence shows that pathways for synthesis of glutathione do exist in the archaeal domain. In observed thermophilic organisms, thiol abundance and redox poise suggest that this system is not directly utilized for protection against oxidative damage. Instead, a more oxidized intracellular environment promotes disulfide bonding, a critical adaptation for protein thermostability. Based on the placement of thermophilic archaea close to the last universal common ancestor in rRNA phylogenies, we hypothesize that thiol-based redox systems are derived from metabolic pathways originally tasked with promoting protein stability.


GABA uptake by purified avian Müller glia cells in culture.
GABA is the main inhibitory aminoacid transmitter present in neurons and glial cells. Its uptake is carried out by specific high-affinity Na(+)/Cl (-) dependent transporters (GATs). It has been reported in the past that, in the avian retina, [(3)H]GABA appears to be exclusively accumulated by horizontal and amacrine cells in the inner nuclear layer, and also by ganglion cells. Purified chick Müller glia cultures were able to take up [(3)H]GABA in a Na(+) and Cl(+) dependent way. Increasing GABA concentration increases GABA uptake by these cells, reaching half-maximal transport efficiency (EC50) around 0.3 mM. [(3)H]GABA uptake by Müller glia neuronal-free cultures was not mediated by neuronal transporters since it was not blocked by NNC-711, but was inhibited by beta-alanine, a specific glial transporter inhibitor. Chick Müller glia in culture express both GAT-1 and GAT-3 GABA transporters. Although mixed neuron-glial dense cultures released GABA upon glutamate, high K[(+) or veratridine stimulation, Müller glial cells did not release [(3)H]GABA upon treatment with these agents, suggesting that different from neurons, transporter mediated GABA release is not a common mechanism operating in these cells. The data also suggest that Müller cells take up GABA unidirectionally, which may constitute an important mechanism of inactivating GABA activity mediated by neurons.


Photoluminescence studies on rare earth titanates prepared by self-propagating high temperature synthesis method.
The laser-induced luminescence studies of the rare earth titanates (R2Ti2O7) (R=La, Nd and Gd) using 355 nm radiation from an Nd:YAG laser are presented. These samples with submicron or nanometer size are prepared by the self-propagating high temperature synthesis (SHS) method and there is no known fluorescence shown by these rare earths in the visible region. Hence, the luminescence transitions shown by the La2Ti2O7 near 610 nm and Gd2Ti2O7 near 767 nm are quite interesting. Though La3+ ions with no 4f electrons have no electronic energy levels that can induce excitation and luminescence processes in the visible region, the presence of the Ti3+ ions leads to luminescence in this region.


[Diagnostic image (333). A girl with vulvar pain].
A 9-year-old girl with a 4 year history of vulvar complaints was thought to be sexually abused but eventually appeared to be suffering from a urethral polyp.


Thyroid cyst mistaken for carotid pseudoaneurysm by MR angiography. Case report.
A normal volunteer for magnetic resonance angiography of the carotid arteries had an abnormal examination that suggested a common carotid pseudoaneurysm. High resolution sonography identified a normal carotid artery immediately adjacent to a thyroid lesion, part of which was cystic and which mimicked carotid aneurysmal disease.


Single-step purification and refolding of recombinant mouse and human myelin oligodendrocyte glycoprotein and induction of EAE in mice.
The extracellular domain of human and rat MOG (ED-MOG) induces experimental autoimmune encephalomyelitis (EAE) when injected into susceptible animals. EAE is a T cell-mediated disease of the central nervous system commonly used as an animal model for human multiple sclerosis. Here, we describe a straightforward procedure for the purification and refolding of mouse and human ED-MOG overexpressed in Escherichia coli as inclusion bodies. Following solubilization and purification using Ni-NTA resin chromatography under denaturing conditions, a column-based refolding proceeded in renaturation buffer supplemented with a glutathione redox buffer system. Using this approach up to 33 mg of highly pure soluble proteins was obtained per liter of expression culture. The ability of purified proteins to induce EAE was evaluated in three strains of mice. We believe that the strategy described here would facilitate researchers to carry out encephalitogenic as well as structure-function studies of this autoantigen. Additionally, we show for the first time that mouse ED-MOG induces severe disease in mice.


NMR analyses on the molecular mechanism of the conformational rigidity of 2-thioribothymidine, a modified nucleoside in extreme thermophile tRNAs.
1H-NMR analyses have been made on the conformations of 2-thioribothymidine (s2T), 2-thiodeoxyribothymidine (s2dT), as well as ribothymidine (T) and deoxyribothymidine (dT). s2T and s2dT exclusively take the anti form rather than the syn form. The C3'-endo-gg form of the sugar moiety is remarkably stabilized on modification of T to s2T, but not on modification of dT to s2dT. The steric effects of the 2-thiocarbonyl group and the 2'-hydroxyl group cause the rigidity of the C3'-endo-gg form of s2T. Such rigidity of s2T probably contributes to the thermostability of 2-thiopyrimidine polyribonucleotides and extreme thermophile tRNAs.


HMMGEP: clustering gene expression data using hidden Markov models.
The package HMMGEP performs cluster analysis on gene expression data using hidden Markov models. HMMGEP, including the source code, documentation and sample data files, is available at http://www.bioinfo.tsinghua.edu.cn:8080/~rich/hmmgep_download/index.html.


Recognition of the E1kE1f cholinesterase genotype in a family segregating three rare genes, E1k, E1f and E1a.
The first identification of the cholinesterase variant E1kE1f is reported from a family study. The evidence is based on the determination of enzymic activity, dibucaine, fluoride and RO2 numbers. Three individuals appear to have this genotype, and family evidence is not at variance with our conclusions. All three individuals will be sensitive to suxamethonium.


An evaluation of the closed mouth mandibular block technique.
This randomised double-blind study compared the efficacy of the closed-mouth and the conventional mandibular block injection techniques in 200 patients requiring anaesthesia for tooth extractions. Results showed the success rate of inferior alveolar nerve anaesthesia with a single injection to be 97% in the conventional group, and 79% in the closed-mouth group. Within 5 min after the injection, 87% of the conventional group as compared with 55% of the closed-mouth group had lip numbness. The conventional and closed-mouth techniques, respectively, yielded 22% and 2% positive aspirations. Long buccal nerve anaesthesia during the closed-mouth injection was achieved in 71% of cases. Both techniques produced similar pain responses, as well as changes in blood pressure and pulse rate. The closed-mouth injection technique produced a greater variety of unexpected symptoms than the conventional. It was concluded that the conventional technique was more effective in blocking the inferior alveolar nerve, and was also faster in producing anaesthesia, but yielded more positive aspirations than the closed-mouth technique.


Evaluation of pelvic ultrasonography in the diagnosis and differentiation of various forms of sexual precocity in girls.
This study was conducted to assess the role of pelvic ultrasound variables in discriminating between normal girls and girls with different forms of sexual precocity, and to establish reliable cut-off limits of pelvic ultrasound measurements for differentiating between these conditions. Eighty-eight girls with different forms of sexual precocity (23 with premature thelarche, 15 with premature pubarche and 50 with central precocious puberty) were enrolled. All diagnoses were based on clinical examination with confirmation using the gonadotropin-releasing hormone-stimulation test. Additionally, 81 prepubertal girls, aged 0-10 years, were included as a control group. For statistical analysis and to facilitate comparisons, the groups were subdivided by age intervals (0-6, > 6-8 and > 8-10 years). All subjects underwent pelvic ultrasound examination for the measurement of uterine length, uterine volume, ovarian volume and the anteroposterior diameter at the fundus divided by the anteroposterior diameter at the cervix (fundal/cervical ratio, (F/C)). Finally, the morphological appearance of the ovaries was assessed. Patients with central precocious puberty had significantly higher values for all the ultrasound variables (with the exception of uterine length in the 1-6-year age group) in comparison to normal girls. Patients with premature thelarche and patients with premature pubarche showed similar pelvic ultrasound parameters to those of normal girls. Ovarian volume was the best parameter for identifying patients with central precocious puberty (a cut-off of 3.04 cm(3) had a sensitivity of 100% and a specificity of 97.1% for age interval 0-6 years, a cut-off of 3.35 cm(3) had a sensitivity of 100% and a specificity of 89.5% for age interval > 6-8 years, and a cut-off of 4.46 cm(3) had a sensitivity of 80.8% and a specificity of 88.5% for age interval > 8-10 years). Uterine length was the best parameter for distinguishing between patients with central precocious puberty and patients with premature thelarche (a cut-off of 3.185 cm had a sensitivity of 85.7% and a specificity of 91.7% for age interval 0-6 years, and a cut-off of 3.83 cm had a sensitivity of 82.4% and a specificity of 90.9% for age interval > 6-8 years). Ultrasound examination of the uterus and ovaries could serve as a complementary tool for the diagnosis of central precocious puberty and, consequently, for the early initiation of appropriate treatment.


Value of pre-therapy 18F-FDG PET/CT radiomics in predicting EGFR mutation status in patients with non-small cell lung cancer.
To assess the predictive power of pre-therapy 18F-FDG PET/CT-based radiomic features for epidermal growth factor receptor (EGFR) mutation status in non-small cell lung cancer. Two hundred and forty-eight lung cancer patients underwent pre-therapy diagnostic 18F-FDG PET/CT scans and were tested for genetic mutations. The LIFEx package was used to extract 47 PET and 45 CT radiomic features reflecting tumor heterogeneity and phenotype. The least absolute shrinkage and selection operator (LASSO) algorithm was used to select radiomic features and develop a radiomics signature. We compared the predictive performance of models established by radiomics signature, clinical variables, and their combinations using receiver operating curves (ROCs). In addition, a nomogram based on the radiomics signature score (rad-score) and clinical variables was developed. The patients were divided into a training set (n = 175) and a validation set (n = 73). Ten radiomic features were selected to build the radiomics signature model. The model showed a significant ability to discriminate between EGFR mutation and EGFR wild type, with area under the ROC curve (AUC) equal to 0.79 in the training set, and 0.85 in the validation set, compared with 0.75 and 0.69 for the clinical model. When clinical variables and radiomics signature were combined, the AUC increased to 0.86 (95% CI [0.80-0.91]) in the training set and 0.87 (95% CI [0.79-0.95]) in the validation set, thus showing better performance in the prediction of EGFR mutations. The PET/CT-based radiomic features showed good performance in predicting EGFR mutation in non-small cell lung cancer, providing a useful method for the choice of targeted therapy in a clinical setting.


BEDwARS: a robust Bayesian approach to bulk gene expression deconvolution with noisy reference signatures.
Differential gene expression in bulk transcriptomics data can reflect change of transcript abundance within a cell type and/or change in the proportions of cell types. Expression deconvolution methods can help differentiate these scenarios. BEDwARS is a Bayesian deconvolution method designed to address differences between reference signatures of cell types and corresponding true signatures underlying bulk transcriptomic profiles. BEDwARS is more robust to noisy reference signatures and outperforms leading in-class methods for estimating cell type proportions and signatures. Application of BEDwARS to dihydropyridine dehydrogenase deficiency identified the possible involvement of ciliopathy and impaired translational control in the etiology of the disorder.


Editorial Commentary: Routine Preoperative Magnetic Resonance Imaging for Hip Arthroscopy Is Wasting Health Care Dollars and Delaying Surgical Intervention: Decision Making Should Be at the Discretion of the Health Care Provider Not Mandated by Health Care Insurers.
Making an accurate preoperative diagnosis is critical to optimizing outcomes after hip arthroscopy. A detailed history, thorough physical examination, imaging studies, and diagnostic injections must all be considered in the decision-making process. In today's health care climate, it is imperative to obtain essential and indicated preoperative information while being mindful of health care dollars. Magnetic resonance imaging (MRI) of the hip has been shown to be a highly sensitive modality for hip and pelvis disorders. However, it is critical to recognize that acetabular labral tears and other hip pathology are highly prevalent in an asymptomatic young adult population. There are certainly situations when an MRI should be obtained (suspected arthritic symptoms, avascular necrosis, synovial disorders, uncommon osseous tumors); however, these patients generally present with atypical symptoms. In addition, obtaining an MRI can delay surgical intervention, which has been shown to lead to inferior outcomes in prior studies. MRI is not imperative when patients present with typical intermittent, deep anterior, lateral, groin pain with prolonged sitting, twisting and pivoting, and transitioning from sitting to standing. The typical physical examination includes positive hip impingement testing (FADIR / anterior impingement test) that recreates the patients presenting complaints. Appropriate imaging includes plain radiographs revealing adequate acetabular coverage (not significantly dysplastic) or acetabular overcoverage (pincer-type femoracetabular impingement), cam-type femoracetabular impingement, and well-maintained joint space on all views, including a false profile radiograph to further evaluate the anterior joint space. Finally, a diagnostic injection can be invaluable to further confirm the hip joint proper as the source of pain. If all of the above criteria are met, I strongly believe an MRI is unlikely to alter the surgical decision-making process. In the end, the treating clinician should determine when an MRI is necessary based on the presenting symptoms and examination, rather than insurers applying a blanket requirement for preauthorization. This physician autonomy would ultimately lead to more efficient and cost-effective patient care. Medicine is an art, and unjustified handcuffing of the artist without evidence could result in inferior results.


A Phase II Study of S-1 for Previously Untreated Elderly Patients with Advanced Non-Small Cell Lung Cancer.
S-1, a novel oral fluoropyrimidine, is active in the treatment of non-small cell lung cancer (NSCLC). However, data on S-1 for elderly patients with NSCLC are insufficient. Eligibility criteria were no prior chemotherapy, stage IIIB or IV NSCLC, performance status 0-1, age >70 years, and adequate hematological, hepatic, and renal functions. Patients received S-1 (40 mg/m(2) twice a day) for 28 consecutive days. This schedule was repeated every 6 weeks. The primary end point was the tumor response rate. Thirty-two patients were enrolled and 31 patients were evaluable for response. The patients' median age was 80 years (range: 71-88). The response rate was 22.6% (95% CI: 11-38). Neutropenia, anemia, thrombocytopenia, febrile neutropenia, and diarrhea of grade ≥ 3 occurred in 6, 6, 10, 3, and 3%, respectively. In elderly patients with previously untreated advanced NSCLC, S-1 appears to be well tolerated and demonstrates encouraging activity.


Carbonyl 13C-detect solution-state protein NMR experiments to circumvent amide-solvent exchange broadening: Application to β2-microglobulin.
The 15N-1H heteronuclear single-quantum correlation (HSQC) technique in protein NMR spectroscopy suffers from line-broadening effects, such as chemical exchange of labile protons with solvent, and exchange broadening for residues undergoing conformational dynamics. The amide resonance of β2-microglobulin residue S88 is not observed in the HSQC spectrum but can be obtained through 13C-detect experiments that circumvent the problem of amide-solvent exchange broadening. Line broadening of S88 resonance beyond detection in the HSQC spectrum is not attributed to conformational exchange but rather to solvent exchange occurring on the order of ~103 s-1.


Autologous muscle-derived cells for the treatment of female stress urinary incontinence: a 2-year follow-up of a Polish investigation.
We evaluated the safety, feasibility and initial effects of therapy with muscle-derived cells (MDCs) for women with stress urinary incontinence (SUI). MDCs were isolated from an upper-arm muscle biopsy from 16 women with SUI. Cells were isolated by enzymatic digestion and expanded in vitro for 8-10 weeks. A quantity of 0.6-25 × 10(6) of the obtained cells were injected transurethrally into the urethral rhabdosphincter of women under local anesthesia. The cells were placed circumferentially at the 9, 12, and 3 O'clock positions with endoscopic guidance. The initial results of the treatment of SUI with adult muscle-derived stem cells demonstrate the safety and feasibility of using these cells. The 2-year follow-up revealed a 75% success rate, with some patients achieving complete improvement (50%) and some patients achieving partial improvement (25%), suggesting that the prospects for this method are encouraging. Stem cell therapy promises to become a minimally invasive method for the regeneration of the urethral rhabdosphincter muscle. Injecting a small number of cells does not preclude obtaining the desired therapeutic result.


Aeromonas hydrophila induced head kidney macrophage apoptosis in Clarias batrachus involves the activation of calpain and is caspase-3 mediated.
The mechanism of macrophage cytotoxicity induced by Aeromonas hydrophila is yet unresolved. We observed A. hydrophila induces Head Kidney Macrophage (HKM) apoptosis in Clarias batrachus, as evident from Hoechst 33342 and AnnexinV-Propidium Iodide staining and presence of oligonucleosomal DNA ladder. Initiation of apoptosis required the bacteria to be alive, be actively phagocytosed into HKM and was dependent on host proteins. Elevated cytosolic calcium and consequent calpain activity that declined following pre-incubation with EGTA, verapamil and nifedipine implicates the role of calcium influx through voltage gated calcium channels and calpain in A. hydrophila-induced HKM apoptosis. Though, calpain-1 and -2 were involved, calpain-2 appeared to be more important in the process. EGTA, verapamil, nifedipine and calpain-2 inhibitor reduced caspase-3 activity and apoptosis. We conclude that A. hydrophila alters cytosolic calcium homeostasis initiating the activation of calpains, more specifically calpain-2, which leads to caspase-3 mediated HKM apoptosis in C. batrachus.


Effect of blood transfusion in combination with Dextran-40 and hypertonic saline solution on cardiopulmonary haemodynamics of endotoxin (lipopolysaccharide) shock in buffalo calves.
The intravenous (i.v.) infusion of lipopolysaccharide (LPS) of E. coli endotoxin in buffalo calves (n = 15) at 5 microg/kg bw per h for 3 h caused a significant (p<0.05) fall in plasma volume, blood volume, haematocrit haemoglobin, and systolic, diastolic and pulse pressure, mean arterial pressure and central venous pressure (CVP), with a marked rise in respiration. Treatment with a combination of i.v. infusion of 7.2% hypertonic saline solution, Plasmex-D-40 (Dextran-40) and blood successfully alleviated hypovolaemia, and raised systolic, diastolic and pulse pressure, mean arterial pressure and central venous pressure. The whole blood was collected from apparently healthy male buffalo calves 24 h prior to infusion and was transfused without cross-matching. No significant fall in haemoglobin, haematocrit and body temperature was observed after transfusion. All these values tended to remain near normal levels. However, this combination of treatment had no effect on high respiratory rate. A one-time blood transfusion did not evoke any cross-reaction and was helpful in raising haematocrit and haemoglobin close to pre-infusion values. The general symptoms of restlessness, respiratory distress, profuse salivation, violent movement of the ears, snoring, intermittent struggle, etc. were markedly reduced. All the treated animals became quiet and lay with eyes open and survived the 7 h of observation.


Botulinum toxin (BoNT) and back pain.
Myofascial pain syndrome is defined as subacute or chronic pain with sensory, motor and autonomic symptoms referred from active trigger points with associated painful dysfunctions. Authors present the usefulness of botulinum toxin A or B (BoNT/A or BoNT/B) injected into target muscles since the toxin is capable of controlling not only the muscular spasm but mostly the pain by alternative mechanisms of action, which are discussed. Posology of BoNT, technical aspects and results are presented. BoNT represents an interesting and useful tool for an adequate management of patients with myofascial pain.


Should we ignore U-235 series contribution to dose?
Environmental Risk Assessment (ERA) methodology for radioactive substances is an important regulatory tool for assessing the safety of licensed nuclear facilities for wildlife, and the environment as a whole. ERAs are therefore expected to be both fit for purpose and conservative. When uranium isotopes are assessed, there are many radioactive decay products which could be considered. However, risk assessors usually assume (235)U and its daughters contribute negligibly to radiological dose. The validity of this assumption has not been tested: what might the (235)U family contribution be and how does the estimate depend on the assumptions applied? In this paper we address this question by considering aquatic wildlife in Canadian lakes exposed to historic uranium mining practices. A full theoretical approach was used, in parallel to a more realistic assessment based on measurements of several elements of the U decay chains. The (235)U family contribution varied between about 4% and 75% of the total dose rate depending on the assumptions of the equilibrium state of the decay chains. Hence, ignoring the (235)U series will not result in conservative dose assessments for wildlife. These arguments provide a strong case for more in situ measurements of the important members of the (235)U chain and for its consideration in dose assessments.


[Culture of safety and clinical risk management].
An error-resistant safety culture can only be achieved through proactive clinical risk management. In April 2019 the Federal Joint Committee once again increased the pressure on hospitals by means of the Quality Promotion and Enforcement Directive (QFD Directive) to take measures within the framework of clinical risk management in order to reduce the error and harm rate and therefore to significantly improve patient safety. In the long term this can only be achieved by positively influencing the safety culture and thus the attitudes and motives of all employees. Clinical risk management should focus on the prevention of so-called sentinel events on the one hand and on the reduction of frequent and avoidable complications on the other hand. This not only improves patient safety but also protects employees from negative consequences. Effective clinical risk management always follows a systemic approach, the 10 fields of action of which are discussed in this article. Large meta-analyses have also confirmed the substantial economic benefit of a clinical risk management.


Review article: current and emerging therapies for acute alcohol-associated hepatitis.
Alcohol-associated hepatitis is an acute manifestation of alcohol-associated liver disease (ALD) and is associated with 30%-40% mortality at 28 days. Abstinence and corticosteroids are the mainstays of treatment, but the latter only improves short-term mortality, so new and improved therapies remain an unmet need. The aim was to review the pathophysiology of alcohol-associated hepatitis and how various targets can be used by current and emerging therapies as treatment. A thorough literature review was conducted on acute alcohol-associated hepatitis, current therapies and therapies under investigation. With the increasing prevalence of alcohol use disorder and ALD, the burden of alcohol-associated hepatitis is also expected to rise. The current understanding of alcohol-associated hepatitis pathophysiology has led to clinical trials of several therapies involving IL-1 antagonism, modification of the gut microbiome and liver regeneration. Corticosteroid therapy for alcohol-associated hepatitis is restricted in its applicability and has limited efficacy. Developing multidisciplinary, patient-centred care models based on digital health technologies, in combination with continued discovery of novel therapies using multiomics data and computational biology techniques will be necessary to tackle the increasing burden of alcohol-associated hepatitis.


A model for evaluating the social performance of construction waste management.
It has been determined by existing literature that a lot of research efforts have been made to the economic performance of construction waste management (CWM), but less attention is paid to investigation of the social performance of CWM. This study therefore attempts to develop a model for quantitatively evaluating the social performance of CWM by using a system dynamics (SD) approach. Firstly, major variables affecting the social performance of CWM are identified and a holistic system for assessing the social performance of CWM is formulated in line with feedback relationships underlying these variables. The developed system is then converted into a SD model through the software iThink. An empirical case study is finally conducted to demonstrate application of the model. Results of model validation indicate that the model is robust and reasonable to reflect the situation of the real system under study. Findings of the case study offer helpful insights into effectively promoting the social performance of CWM of the project investigated. Furthermore, the model exhibits great potential to function as an experimental platform for dynamically evaluating effects of management measures on improving the social performance of CWM of construction projects.


Use of preoperative ultrasonography as guidance for neck dissection in patients with papillary thyroid carcinoma.
Preoperative neck ultrasonography (US) may detect nodal metastases of papillary thyroid carcinoma (PTC) but its utility in detecting metastases at specific neck subsites and levels is not known. We therefore evaluated preoperative US in detecting cervical metastases of PTC according to neck subsites and levels. Preoperative US was performed in 133 new patients to detect metastases at three central cervical subsites and five lateral cervical levels. All patients underwent total thyroidectomy and bilateral central neck dissection. Thirty-four patients with lateral nodal metastases underwent modified radical neck dissection. Lymph node metastases to the central and lateral cervical compartments were identified in 57.9% and 25.6%, respectively. The sensitivity and specificity of US for detecting central nodal metastasis were 61.0% and 92.8%, respectively. In the lateral neck, US detected non-palpable lymph node metastases in 6 of 34 patients (17.6%). Overall, US was >85.0% specific at all cervical subsites and levels. Preoperative US may detect cervical metastases of PTC and may assist in determining the necessity and extent of neck dissection in PTC patients.


The role of NPY in the mediation of orexin-induced hypothermia.
The mediation of orexin-A-induced hypothermia was investigated. Different doses of orexin-A (140-560 pmol) were administered intracerebroventricularly (i.c.v.) to adult male rats, and the colon temperature was used as an index of the thermoregulatory action. Orexin-A decreased both the basal colon temperature and the lipopolysaccharide-induced fever and exhibited a bell-shaped dose-response curve. I.c.v. pretreatment with neuropeptide Y (NPY) antiserum 24 h before orexin administration significantly decreased the hypothermic effect of orexin-A. These data strengthen the hypothesis that this appetite-regulating peptide might also play a role in thermoregulation, and its hypothermic effect seems to be mediated at least partially by NPY.


Despite Equivalent Medicare Reimbursement, Facility Costs for Outpatient Total Knee Arthroplasty Are Higher Than Unicompartmental Knee Arthroplasty.
With the recent removal of total knee arthroplasty (TKA) from the Centers for Medicare and Medicaid Services (CMS) Inpatient Only list, facility reimbursement for outpatient TKA now falls under the Outpatient Prospective Payment System at the same rate as unicompartmental knee arthroplasty (UKA). The purpose of this study was to compare true facility costs of patients undergoing outpatient TKA with those undergoing UKA. We reviewed a consecutive series of 2310 outpatient TKA and 231 UKA patients from 2018 to 2019. Outpatient status was defined as a hospital stay of less than 2 midnights. Facility costs were calculated using a time-driven, activity-based costing algorithm. Implants, supplies, medications, and personnel costs were compared between outpatient TKA and UKA patients. A multivariate analysis was performed to control for confounding medical and demographic variables. When compared with patients undergoing UKA, outpatient TKA patients had higher implant costs ($3403 vs $3081; P < .001) and overall hospital costs ($6350 vs $5594; P < .001). Outpatient TKA patients had a greater length of stay (1.2 vs 0.5 days; P < .001) and greater postoperative personnel costs ($783 vs $166; P < .001) than UKA patients. When controlling for comorbidities, outpatient TKA was associated with a $803 (P < .001) increase in overall facility costs compared with UKA. Despite equivalent reimbursement from CMS as UKA, outpatient TKA has increased facility costs to the hospital. Although implant costs can vary greatly by institution, CMS should consider appropriately reimbursing outpatient TKA for the additional personnel costs when compared with UKA.


Diaminoalkanes functionalized graphene oxide as corrosion inhibitors against carbon steel corrosion in simulated oil/gas well acidizing environment.
Experimental weight loss and electrochemical measurements were used at ambient and high temperatures to evaluate the corrosion inhibition efficacies of diaminodecane functionalized graphene oxide (DAD-GO) and diaminododecane functionalized graphene oxide (DADD-GO) against carbon steel corrosion in 15.0 %HCl, mimicking an acidizing environment in an oil/gas well. The GO was made from waste graphite and then grafted with the diaminoalkanes (DAD & DADD). The GO and functionalized GOs were described using FTIR, Raman, TEM, and TGA. Concentration and temperature effects on the inhibitors'performance were also looked into. The inhibition efficiency increased with concentration at room temperature, reaching a maximum of 84 % for DAD-GO and 78 % for DADD-GO at a concentration of 5 ppm for both. At the temperatures studied, the inhibitors performed well at extremely low concentrations; however, as the temperature rises, the inhibitor's performance decreases. According to the PDP measurement, the inhibitors function primarily as mixed-type inhibitors. The Langmuir adsorption theory was found to be followed by thestudied compound. AFM, SEM, EDX, and FTIR characterization of the steel surfaces revealed that the functionalized GOs molecules adsorbed on the steel to create a protective layer that insulated the steel from aggressiveacid assault after the immersion time (24 h) in the inhibited solutions. DFT calculations were utilized to determine the relative stability of functionalized GOs toGOand to learn more about the inhibitor molecules' interactions with the steel surface. The DFT calculations corroborated the experimental findings. This study is important in tackling two significant environmental concerns: corrosion and waste management because GO is manufactured from waste graphite.


Integrated one-dimensional CuO-nanowire arrays/Cu-foam nanoarchitecture for ultrahigh sensitive and non-enzymatic electrochemical determination of histamine levels in different-bacteria fermented mandarin fish.
Integrated one-dimensional CuO-nanowire arrays/Cu-foam (CuO-NWAs/Cu-foam) nanostructure, which was fabricated by oxidation and calcination, has been newly utilized as non-enzymatic electrocatalytic electrode for exploring histamine level. Under optimal condition of pH at 13 and potential at 0.55 V (vs Ag/Ag/Cl), the sensitivity of CuO-NWAs/Cu-foam electrode towards non-enzymatic electrochemical histamine determination presented as high as 12.94 mA mM-1 cm-2, linear range spanned between 0.5 and 1046 μM, a detection limit (S/N = 3) was about 44 nM. The unprecedented causes of ultrahigh sensitivity were physically contributed to enhancing active surface area and declining charge transfer resistance. More crucially, the outstanding selectivity, stability and reproducibility facilitated its practical capacity on evaluating histamine levels in different-bacteria fermented mandarin fish, which triggered the potential feasibility for commercializing non-enzymatic electrochemical determination of histamine with high sensitivity, reliable precision and low expenditure.