Detection of Bacillus piliformis by specific amplification of ribosomal sequences.
In an effort to explore a sensitive species-specific detection system using the polymerase chain reaction (PCR) for B. piliformis, we sequenced 16S ribosomal DNA (rDNA) of the organism (MSK strain) isolated from the mouse and compared it with known rDNA sequences of the RJ strain isolated from the rat. Sequence homology between the MSK strain and the RJ strain was over 97%, but homology between the MSK strain and other bacterial species was less (70-83%). The results indicated that the sequences included B. piliformis species-specific regions. On the basis of the sequences, we designed a PCR primer set which amplifies B. piliformis rDNA specifically. The PCR with the primer set detected not only these two strains but also an HN strain of hamster origin, although it did not detect other organisms. Therefore, this primer set was considered to be specific for B. piliformis species. More than one organism (RJ strain) could be detected by the PCR method. Nine Jcl:Wistar rats were infected perorally with 2x10(4) RJ strain organisms, and three rats each were sacrificed on days 1, 3 and 5 postinoculation (p.i.) to investigate the presence of the organism in the liver, heart, cecum, spleen and mesenteric lymph nodes by PCR and the immunofluorescence test. On days 1 and 3 p.i., B. piliformis was not detected in any tissues of the six rats, but B. piliformis was detected in two of the three rats sacrificed on day 5 p.i. The presence of the pathogen was seen in both liver and heart (1/3), or in the cecum (1/3) by both methods.(ABSTRACT TRUNCATED AT 250 WORDS)


High Rate of Positive Circumferential Resection Margins Following Rectal Cancer Surgery: A Call to Action.
To identify predictors of positive circumferential resection margin following rectal cancer resection in the United States. Positive circumferential resection margin is associated with a high rate of local recurrence and poor morbidity and mortality for rectal cancer patients. Prior study has shown poor compliance with national rectal cancer guidelines, but whether this finding is reflected in patient outcomes has yet to be shown. Patients who underwent resection for stage I-III rectal cancer were identified from the 2010-2011 National Cancer Database. The primary outcome was a positive circumferential resection margin. The relationship between patient, hospital, tumor, and treatment-related characteristics was analyzed using bivariate and multivariate analysis. A positive circumferential resection margin was noted in 2859 (17.2%) of the 16,619 patients included. Facility location, clinical T and N stage, histologic type, tumor size, tumor grade, lymphovascular invasion, perineural invasion, type of operation, and operative approach were significant predictors of positive circumferential resection margin on multivariable analysis. Total proctectomy had nearly a 30% increased risk of positive margin compared with partial proctectomy (OR 1.293, 95%CI 1.185-1.411) and a laparoscopic approach had nearly 22% less risk of a positive circumferential resection margin compared with an open approach (OR 0.882, 95%CI 0.790-0.985). Despite advances in surgical technique and multimodality therapy, rates of positive circumferential resection margin remain high in the United States. Several tumor and treatment characteristics were identified as independent risk factors, and advances in rectal cancer care are necessary to approach the outcomes seen in other countries.


Seronegative arthritis associated with serological evidence of Yersinia infection in Australia.
Infection due to yersinia enterocolitica is a common antecedent illness in patients with reactive arthritis in Scandinavia, but appears to be less frequent in other countries. In order to examine the frequency of yersinia infection in patients with seronegative arthritis in Australia we examined 22 patients, 15 with ankylosing spondylitis (AS) and seven with Reiter's syndrome (RS). A sensitive ELISA assay was used to detect serum antibodies to the most common serotypes. Six patients (29%) had positive yersinia serology, all were HLA B27 and four had a history of diarrhea preceding the onset of their disease. Four patients with positive yersinia serology had AS and two had RS. Antibodies were directed against Y. enterocolitica biotype 0:3 in three cases, Y. enterocolitica 0:9 in two cases and Y. enterocolitica 0:8 in one subject. Twenty-nine control subjects (13 HLA B27) had no serum antibodies to yersinia. The results of this study indicate that preceding yersinia infection occurs in a significant (p less than 0.05; compared to controls) proportion of patients with HLA B27 related seronegative arthropathies.


Integrating Genome-Wide Association and eQTLs Studies Identifies the Genes and Gene Sets Associated with Diabetes.
To identify novel candidate genes and gene sets for diabetes. We performed an integrative analysis of genome-wide association studies (GWAS) and expression quantitative trait loci (eQTLs) data for diabetes. Summary data was driven from a large-scale GWAS of diabetes, totally involving 58,070 individuals. eQTLs dataset included 923,021 cis-eQTL for 14,329 genes and 4,732 trans-eQTL for 2,612 genes. Integrative analysis of GWAS and eQTLs data was conducted by summary data-based Mendelian randomization (SMR). To identify the gene sets associated with diabetes, the SMR single gene analysis results were further subjected to gene set enrichment analysis (GSEA). A total of 13,311 annotated gene sets were analyzed in this study. SMR analysis identified 6 genes significantly associated with fasting glucose, such as C11ORF10 (p value = 6.04 × 10-8), MRPL33 (p value = 1.24 × 10-7), and FADS1 (p value = 2.39 × 10-7). Gene set analysis identified HUANG_FOXA2_TARGETS_UP (false discovery rate = 0.047) associated with fasting glucose. Our study provides novel clues for clarifying the genetic mechanism of diabetes. This study also illustrated the good performance of SMR approach and extended it to gene set association analysis for complex diseases.


Cooperative Tridentate Hydrogen-Bonding Interactions Enable Strong Underwater Adhesion.
Multidentate hydrogen-bonding interactions are a promising strategy to improve underwater adhesion. Molecular and macroscale experiments have revealed an increase in underwater adhesion by incorporating multidentate H-bonding groups, but quantitatively relating the macroscale adhesive strength to cooperative hydrogen-bonding interactions remains challenging. Here, we investigate whether tridentate alcohol moieties incorporated in a model epoxy act cooperatively to enhance adhesion. We first demonstrate that incorporation of tridentate alcohol moieties leads to comparable adhesive strength with mica and aluminum in air and in water. We then show that the presence of tridentate groups leads to energy release rates that increase with an increase in crack velocity in air and in water, while materials lacking these groups do not display rate-dependent adhesion. We model the rate-dependent adhesion to estimate the activation energy of the interfacial bonds. Based on our data, we estimate the lifetime of these bonds to be between 2 ms and 6 s, corresponding to an equilibrium activation energy between 23kBT and 31kBT. These values are consistent with tridentate hydrogen bonding, suggesting that the three alcohol groups in the Tris moiety bond cooperatively form a robust adhesive interaction underwater.


Stent infection and pseudoaneurysm formation after carotid artery stent treated by excision and in situ reconstruction with polytetrafluoroethylene graft: A case report.
Stent infection after carotid artery stenting (CAS) can be a life-threatening postoperative complication, but there is a paucity of data due to its exceedingly low frequency. We report a case of stent infection with pseudoaneurysm formation after CAS that was treated through replacing the infected stent and pseudoaneurysm with a polytetrafluoroethylene (PTFE) synthetic vessel graft. An 86-year-old man was treated for the right internal carotid artery with CAS in local hospital. One month after stenting, he suffered aspiration pneumonia and septicemia. Three months after stenting, swelling and tenderness of the right side of his neck appeared. His general condition deteriorated due to septicemia and he was unable to ingest anything by mouth as a result of decreasing levels of consciousness. He was transferred to our hospital. Computed tomography and digital subtraction angiography showed the presence of a pseudoaneurysm around the stent. The neck mass enlarged daily and surgical intervention was required to prevent closure of the airway. Stent and pseudoaneurysm resection and in situ reconstruction with a PTFE synthetic vessel graft were performed. The patient returned to his local hospital 36 days after surgery and had a modified Rankin Score of 5. Although the risk of reinfection is high due to the nature of artificial material, stent/pseudoaneurysm resection and in situ reconstruction with a PTFE synthetic vessel graft might be one of the best options for patients suffering stent infection after CAS. To the best of our knowledge, this is the first report of treatment using this material.


Neonatal abstinence syndrome: Neurobehavior at 6 weeks of age in infants with or without pharmacological treatment for withdrawal.
Use and abuse of prescription opioids and concomitant increase in Neonatal Abstinence Syndrome (NAS), a condition that may lead to protracted pharmacological treatment in more than 60% of infants, has tripled since 2000. This study assessed neurobehavioral development using the NICU Network Neurobehavioral Scale in 6-week old infants with prenatal methadone exposure who did (NAS+; n = 23) or did not (NAS-; n = 16) require pharmacological treatment for NAS severity determined by Finnegan Scale. An unexposed, demographically similar group of infants matched for age served as comparison (COMP; n = 21). NAS+, but not NAS- group, had significantly lower scores on the regulation (p < .01) and quality of movement (p < .01) summary scales than the COMP group. The NAS+ and NAS- groups had higher scores on the stress-abstinence scale than the COMP group (p < .05). NAS diagnosis (NAS +) was associated with poorer regulation and quality of movement at 6 weeks of age compared to infants without prenatal methadone exposure from the same demographic.


The impact of recipient history of cardiovascular disease on kidney transplant outcome.
Cardiovascular disease (CVD) leads to increased mortality rates among renal transplant recipients; however, its effect on allograft survival has not been well studied. The records from the United States Renal Data System and the United Network for Organ Sharing from January 1, 1995, through December 31, 2002, were examined in this retrospective study. The outcome variables were allograft survival time and recipient survival time. The primary variable of interest was CVD, defined as the presence of at least one of the following: cardiac arrest, myocardial infarction, dysrhythmia, congestive heart failure, ischemic heart disease, peripheral vascular disease, and unstable angina. The Cox models were adjusted for potential confounding factors. Of the 105,181 patients in the data set, 20,371 had a diagnosis of CVD. The presence of CVD had an adverse effect on allograft survival time (HR 1.12, p < 0.001) and recipient survival time (HR 1.41, p < 0.001). Among the subcategories, congestive heart failure (HR 1.14, p < 0.005) and dysrhythmia (HR 1.26, p < 0.05) had adverse effects on allograft survival time. In addition to increasing mortality rates, CVD at the time of end-stage renal disease onset is also a significant risk factor for renal allograft failure. Further research is needed to evaluate the role of specific forms of CVD in allograft and recipient outcome.


Blastogenic responses of human lymphocytes to a streptococcal preparation OK-432 and its fractions.
This study was undertaken to examine the blastogenic responses of PBL to Streptococcal preparation OK-432 and its fractions. The results showed that OK-432 and its fractions, Su-PR and PM, have the mitogenic activity against human lymphocytes. The demonstration that PBL which had been cultured with OK-432 expressed IL-2 receptors and the blastogenic responses of PBL to OK-432 were inhibited by anti-IL-2 antibody suggested that IL-2 and IL-2 receptors might play a central role in OK-432-induced proliferation of human lymphocytes.


Pancreatic enzymes sustain systemic inflammation after an initial endotoxin challenge.
Sepsis is accompanied by severe inflammation whose mechanism remains uncertain. We recently demonstrated that pancreatic proteases in the ischemic intestine have the ability to generate powerful inflammatory mediators that can be detected in the portal vein and in the general circulation. This study was designed to examine several circulatory and inflammatory indices during experimental endotoxemia and intraintestinal pancreatic protease inhibition. Immediately after intravenous endotoxin administration, the small intestine was subjected to intraluminal lavage with and without gabexate mesilate, an inhibitor of pancreatic proteases. Shams and rats without lavage served as controls. Hemodynamics, leukocyte (neutrophil and monocyte), and endothelial cell activation, as well as organ injury in the intestine and the cremaster muscle, were examined. After endotoxin administration, control rats developed hypotension, tachycardia, hyperventilation, and leukopenia. The intestine and plasma contained mediators that activated leukocytes. The leukocyte-endothelial interaction within the cremaster muscle microcirculation was enhanced. Endotoxin administration resulted in elevated interleukin-6 plasma levels. Histologic evidence indicated liver and intestinal injury. In contrast, blockade of pancreatic proteases in the intestinal lumen significantly improved hemodynamic parameters and reduced all indices of inflammation in plasma and cell injury in skeletal muscle microcirculation. Inflammatory mediators derived from the intestine by pancreatic proteases may be involved in the prolonged inflammatory response and sustain symptoms of sepsis after endotoxin challenge.


3D Color Power Angio imaging: a new method to assess intracervical vascularization in benign and pathological conditions.
It is well known that angiogenesis is a fundamental event in the growth of tumors as well as in physiological conditions. In an ongoing prospective study involving eight women, we investigated the microvasculature within the cervix by the use of 3D Color Power Angio imaging. The ultrasound equipment was used in conjunction with specialized software providing high-resolution '3D-Angiomode'. The system provides the ability to visualize blood flow in small vessels that are undetectable by conventional color Doppler techniques and also to study the architecture and determine the number of blood vessels. Comparison of the vessels in the normal cervix with those in the cervix affected by carcinoma or bacterial or viral infection demonstrated that, in malignant tissue, there is a chaotic network of tortuous vessels traversing the tumor mass, whereas, in benign tissue or tissue that is inflamed as a result of infection, the course of the vessels has a regular structure.


Gas-Sensing Transcriptional Regulators.
Gas molecules are ubiquitous in the environment and are used as nutrient and energy sources for living organisms. Many organisms, therefore, have developed gas-sensing systems to respond efficiently to changes in the atmospheric environment. In microorganisms and plants, two-component systems (TCSs) and transcription factors (TFs) are two primary mechanisms to sense gas molecules. In this review, gas-sensing transcriptional regulators, TCSs, and TFs, focusing on protein structures, mechanisms of gas molecule interaction, DNA binding regions of transcriptional regulators, signal transduction mechanisms, and gene expression regulation are discussed. At first, transcriptional regulators that directly sense gas molecules with the help of a prosthetic group is described and then gas-sensing systems that indirectly recognize the presence of gas molecules is explained. Overall, this review provides a comprehensive understanding of gas-sensing transcriptional regulators in microorganisms and plants, and proposes a future perspective on the use of gas-sensing transcriptional regulators.


Experience with an electronic brachytherapy technique for intracavitary accelerated partial breast irradiation.
Phase IV study evaluated the safety and device performance of an electronic brachytherapy system (Axxent Electronic Brachytherapy System) as adjuvant therapy for early-stage breast cancer. Patients were > or =50 years of age and had completely resected invasive ductal carcinoma or ductal carcinoma in situ (<2.0 cm), with N0 M0 and negative microscopic margins of > or =1 mm. The balloon applicator was placed in a closed cavity with a balloon surface to skin distance of > or =7 mm. The prescribed dose was 3.4 Gy/fraction prescribed to 1 cm beyond the balloon surface twice daily (BID) for 10 fractions. Of 65 patients consented, 21 (32%) were not eligible for treatment, and 44 (68%) were treated, with 6-months follow-up in 43 and 1-year follow-up in 36. The prescribed radiation treatment was successfully delivered in 42/44 (95.4%) patients; one was unsuccessful due to a controller issue and the other declined the final fraction following a balloon deflation. Side effects were as anticipated and generally manageable. Four CTCAE v3 grade 3 toxicities were reported: blistering (1), breast tenderness (1), and moist desquamation (2); all have resolved. The most common grade 2 toxicity was erythema. There were no device-related serious adverse events. Early experience demonstrates that the electronic brachytherapy system performed as expected. Electronic brachytherapy has similar acute toxicity profiles to other high dose rate approaches for accelerated partial breast irradiation and offers the convenience of having the treatment in an unshielded room.


Kinematics of the MATCO hip simulator and issues related to wear testing of metal-metal implants.
Metal-metal hip implants have been used clinically in Europe to reduce the risk of wear particle induced osteolysis. Joint simulator devices could provide useful information for design improvement of the modern generation of metal-metal hip implants. Early wear results for metal-metal hip specimens were obtained using a MATCO hip simulator. A detailed kinematic analysis was developed for the MATCO simulator and applied to two of the wear experiments to predict the starting surface motion, contact zone and lubricant film thickness. It was shown that points on cup surfaces were not subjected to a reciprocating interaction with the head during wear at the beginning of testing but as wear proceeded, it was suggested that, in some cases, reciprocating interaction did occur on the cup surface. Comparison between simulator and in vivo kinematics suggested a more realistic representation for cup than for head wear. In the simulator, the Hertzian contact zone moved in a circular path over the cup surface and changed in size in correspondence with the applied load. Elastohydrodynamic lubrication was considered to be possible in the simulator, with estimated fluid film thickness as great as 0.1 micron. However, such thick films were not likely to have occurred at the start of the two wear tests which were examined in detail, although some mixed film lubrication might have accounted for the relatively low wear of one of the specimens. The inclusion of kinematic details, contact mechanics and elastohydrodynamic lubrication analysis in simulator testing protocols and in design of metal metal hip implants was recommended.


Evaluation of the effects of the North Carolina Improved Pregnancy Outcome Project: implications for state-level decision-making.
This study was designed to assess the effects of the North Carolina Improved Pregnancy Outcome (IPO) Project on use of prenatal care and incidence of low birthweight among its primarily Black registrants . Weighted least squares and stratified analysis procedures were used to scrutinize vital statistics data for subpopulation effects. IPO services were received by 51.7 per cent of Black women in the counties served by the project. For all Black registrants , the risk of receiving less than adequate prenatal care was 55.1 per cent of that of the comparison group. For Black teenage registrants , the risk was even less: 37.2 per cent of that of the comparison group. Nevertheless, no corresponding effects on the incidence of low birthweight could be detected. The evaluation methods used in this study can be applied to programs for mothers and infants in other locales to generate useful and practical information for state-level decision-making.


Surgical Septal Myectomy for the Treatment of Residual Left Ventricular Outflow Tract Obstruction Following Failed Alcohol Septal Ablation.
The reasons of residual left ventricular outflow tract (LVOT) obstruction following alcohol septal ablation (ASA) remain unclear, and outcomes of myectomy following failed ASA remain underreported.Thirteen symptomatic patients (10 women, a median age of 60.0 years) who underwent septal myectomy following failed ASA were reviewed. The patients were followed up for a median of 6 months. The clinical characteristics and outcomes of these patients were analyzed and were compared with those of 178 patients who underwent isolated myectomy without previous ASA at our institution during the same period.In the first ASA procedure, the median number of septal perforator arteries injected was 1.0 with the median value of peak creatine kinase following ablation of 978.5 U/L.Uncontrollable extent and location of infarcted myocardium caused by ablation and mitral subvalvular anomalies were found in four (30.8%) and seven (53.8%) patients, respectively. No operative or follow-up deaths occurred. The median maximum LVOT gradients fell from preoperative 112.0 to 8.5 mmHg at follow-up (P < 0.001). Compared with controls, patients with failed ASA had a higher proportion of mitral subvalvular anomalies (53.8% versus 13.5%, P = 0.001) and developed a higher incidence of complete atrioventricular block following myectomy (15.4% versus 1.7%, P = 0.038).Low institutional or operator experience with ablation, uncontrollable extent and location of infarcted myocardium caused by ablation, and mitral subvalvular anomalies may be reasons for failed ASA. Surgical myectomy for the treatment of residual LVOT obstruction after unsuccessful ASA may be associated with favorable results.


Development of a self-calibration method for real-time monitoring of SO2 ship emissions with UV cameras.
Self-calibration of UV cameras was demonstrated for the first time. This novel method has the capability of real-time continuous calibration by using the raw images at 310 nm and 330 nm without changing the viewing direction or adding any additional equipment. The methodology was verified through simulations and experiments and demonstrated to be of greatly improved effectiveness and accuracy. The errors of self-calibration mothed are estimated by comparison with the differential optical absorption spectroscopy (DOAS) approach, and it can be reduced to 1.8% after filter transmittance corrections. The results show that the self-calibration method appears to have great potential as a future technique for quantitative and visual real-time monitoring of SO2 emissions from ships and other point sources (such as oil refineries, power plants, or more broadly, any industrial stack) when the field of view (FOV) of the system is not completely covered by the SO2 plumes.


The analysis of small-sample multivariate data.
Clinical pharmacology studies typically consist of few subjects per treatment group, but with many, possibly highly correlated, measurements taken per subject. Permutational methods for testing equality of the multivariate treatment means when the number of variables exceeds the number of independent subjects have been developed, but are highly computationally intensive. In this paper, a parametric test was derived, using Edgeworth expansions, for the case of two groups, and compared with competing test statistics proposed by Mercante and Johnson (7), Dempster (5), Chung and Fraser (3), Mantel and Valand (6). The proposed test compares favorably with the others in terms of type I error rate, as well as power, and has the advantages of not requiring computationally intensive resources and being easily extendable to more than two groups.


Effect of casein kinase 1α activator pyrvinium pamoate on erythrocyte ion channels.
Pharmacological modification of protein kinase CK1 (casein kinase 1) has previously been shown to influence suicidal erythrocyte death or eryptosis, which is triggered by activation of Cl(-)-sensitive Ca(2+)-permeable cation channels. Ca(2+) entering through those channels stimulates cell membrane scrambling and opens Ca(2+)-activated K(+)-channels resulting in KCl exit and thus cell shrinkage. The specific CK1-inhibitor D4476 (1 µM) blunted, whereas the specific CK1 αactivator pyrvinium pamoate (10 µM) enhanced cell membrane scrambling. The substances were at least partially effective through modification of cytosolic Ca(2+)-activity. The present study explored, whether pyrvinium pamoate indeed influences Cl(-)-sensitive cation-channels in erythrocytes. As a result, removal of Cl(-)increased Fluo3-fluorescence (reflecting cytosolic Ca(2+)-activity), triggered cell membrane scrambling (apparent from annexin-V-binding), and decreased forward scatter (pointing to cell shrinkage). Pyrvinium pamoate significantly augmented the effect of Cl(-)-removal on Fluo3 fluorescence and annexin-V-binding, but blunted the effect on forward scatter. According to whole cell patch clamp recording, Cl(-)removal activated a cation current, which was significantly enhanced by pyrvinium pamoate. Pyrvinium pamoate inhibited Ca(2+)-activated K(+)-channels. Ca(2+)-ionophore ionomycin (1 µM) decreased forward scatter, an effect significantly blunted by pyrvinium pamoate. In conclusion, pyrvinium pamoate activates Cl(-)-sensitive Ca(2+)-permeable cation channels with subsequent Ca(2+)-entry and inhibits Ca(2+)-activated K(+)-channels thus blunting the stimulating effect of Ca(2+) on those channels, K(+)-exit and thus cell shrinkage.


An immobilized hydrogenase from Alcaligenes eutrophus H-16.
Alcaligenes Eutrophus H-16 was grown in continuous culture under conditions which induced hydrogenase production. The hydrogenase enzyme was extracted, partially purified and immobilized on porous glass. This enzyme was then studied both in solution and in immobilized form as a possible candidate for a number of industrial applications. It proved to have a stability (storage and operational) which was highly temperature dependent. Temperatures near freezing caused the enzyme to retain its activity for long periods of time. Although its kinetics were more favorable at elevated temperatures of up to 40 degrees C, the loss of stability outweighed this gain substantially. The effects of buffer type and pH on enzyme activity were also studied. This enzyme has only a modest sensitivity to destruction by oxygen during storage, in contrast to hydrogenases produced by several other microorganisms.


The Twofold Role of 12-Hydroxyoctadecanoic Acid (12-HOA) in a Ternary Water-Surfactant-12-HOA System: Gelator and Co-Surfactant.
Gelled lyotropic liquid crystals can be formed by adding a gelator to a mixture of surfactant and solvent. If the gel network and the liquid-crystalline phase coexist without influencing each other, the self-assembly is called orthogonal. In this study, the influence of the organogelator 12-hydroxyoctadecanoic acid (12-HOA) on the lamellar and hexagonal liquid crystalline phases of the binary system H₂O⁻C12E₇ (heptaethylene glycol monododecyl ether) is investigated. More precisely, we added 12-HOA at mass fractions from 0.015 to 0.05 and studied the resulting phase diagram of the system H₂O⁻C12E₇ by visual observation of birefringence and by ²H NMR spectroscopy. In addition, the dynamic shear moduli of the samples were measured in order to examine their gel character. The results show that 12-HOA is partly acting as co-surfactant, manifested by the destabilization of the hexagonal phase and the stabilization of the lamellar phase. The higher the total surfactant concentration, the more 12-HOA is incorporated in the surfactant layer. Accordingly, its gelation capacity is substantially reduced in the surfactant solution compared to the system 12-HOA⁻n-decane, and large amounts of gelator are required for gels to form, especially in the lamellar phase.


Loss of functional GABA(A) receptors in the Alzheimer diseased brain.
The cholinergic and glutamatergic neurotransmission systems are known to be severely disrupted in Alzheimer's disease (AD). GABAergic neurotransmission, in contrast, is generally thought to be well preserved. Evidence from animal models and human postmortem tissue suggest GABAergic remodeling in the AD brain. Nevertheless, there is no information on changes, if any, in the electrophysiological properties of human native GABA receptors as a consequence of AD. To gain such information, we have microtransplanted cell membranes, isolated from temporal cortices of control and AD brains, into Xenopus oocytes, and recorded the electrophysiological activity of the transplanted GABA receptors. We found an age-dependent reduction of GABA currents in the AD brain. This reduction was larger when the AD membranes were obtained from younger subjects. We also found that GABA currents from AD brains have a faster rate of desensitization than those from non-AD brains. Furthermore, GABA receptors from AD brains were slightly, but significantly, less sensitive to GABA than receptors from non-AD brains. The reduction of GABA currents in AD was associated with reductions of mRNA and protein of the principal GABA receptor subunits normally present in the temporal cortex. Pairwise analysis of the transcripts within control and AD groups and analyses of the proportion of GABA receptor subunits revealed down-regulation of α1 and γ2 subunits in AD. In contrast, the proportions of α2, β1, and γ1 transcripts were up-regulated in the AD brains. Our data support a functional remodeling of GABAergic neurotransmission in the human AD brain.


Knowledge, attitude, and practices of operating theatre staff towards environmentally sustainable practices in the operating theatres.
Successful implementation of environmentally sustainable practices in the operating theatre (OT) requires stakeholder engagement. We evaluate the knowledge, attitudes, and practices of OT users in our institution towards sustainable practices in the OT. A survey was conducted among OT users in August 2022. Respondents completed a 44-question anonymised online survey covering sustainability in (1) knowledge, (2) attitude, (3) practice, and (4) proposed changes to current practices. Points were assigned to knowledge (15 points) and attitude (40 points) sections. Practice was evaluated based on proportion of measures practiced. Appropriate statistical tests were used, with significance p < 0.05. Data are presented as mean ± standard deviation (SD) or proportion (%). Among 149 respondents were doctors (n = 76), non-doctors (n = 45), and medical students (n = 28). Doctors scored highest in knowledge of sustainability (8.58 ± 1.83) compared to non-doctors and medical students (7.62 ± 1.75, 8.39 ± 1.87). Positive attitudes towards sustainability correlated with years of experience (p < 0.01). Non-doctors were more likely to practice sustainable measures, versus doctors (61 vs 52%, p < 0.01). Most (69%) respondents were unwilling to adopt any practice changes. The least popular measure was replacement of standard hand scrubbing with alcohol-based hand rub, considered unsafe by 74% of respondents. Despite positive attitudes towards sustainable measures, there remains wariness of practice changes, which should be addressed by educational campaigns.


A young infant with severe acute respiratory syndrome.
Severe acute respiratory syndrome (SARS), a new contagious respiratory disease associated with a novel coronavirus, has spread worldwide and become a global health concern after its first outbreak in Guangdong Province of the People's Republic of China in November 2002. The clinical presentation and the radiologic, hematologic, biochemical, and microbiologic findings of a 56-day-old male infant with SARS are described. Some clinical and laboratory features are similar to those reported in adult and pediatric patients. However, this infant had a more severe clinical course as compared with the older children. This is the youngest patient with symptomatic SARS reported to date.


Gas Chromatography/Mass Spectrometry-Based Metabolite Profiling of Nutrients and Antinutrients in Eight Lens and Lupinus Seeds (Fabaceae).
Lens culinaris and several Lupinus species are two legumes regarded as potential protein resources aside from their richness in phytochemicals. Consequently, characterization of their metabolite composition seems warranted to be considered as a sustainable commercial functional food. This study presents a discriminatory holistic approach for metabolite profiling in accessions of four lentil cultivars and four Lupinus species via gas chromatography/mass spectrometry. A total of 107 metabolites were identified, encompassing organic and amino acids, sugars, and sterols, along with antinutrients, viz., alkaloids and sugar phosphates. Among the examined specimens, four nutritionally valuable accessions ought to be prioritized for future breeding to include Lupinus hispanicus, enriched in organic ( ca. 11.7%) and amino acids ( ca. 5%), and Lupinus angustifolius, rich in sucrose ( ca. 40%), along with two dark-colored lentil cultivars 'verte du Puy' and 'Black Beluga' enriched in peptides. Antinutrient chemicals were observed in Lupinus polyphyllus, owing to its high alkaloid content. Several species-specific markers were also revealed using multivariate data analyses.


Models for biological trinuclear copper clusters. Characterization and enantioselective catalytic oxidation of catechols by the copper(II) complexes of a chiral ligand derived from (S)-(-)-1,1'-binaphthyl-2,2'-diamine.
The dinuclear and trinuclear Cu(II) complexes of an octadentate ligand derived from (S)-1,1'-binaphthyl-2,2'-diamine have been prepared and characterized by UV/Vis, CD, EPR and NMR spectroscopy. The ligand contains two tridentate aminobis(benzimidazole) donor arms connected to a central bidentate diaminobinaphthyl linker, which hosts the chiral unit. In the dinuclear Cu complex the ligation occurs essentially within the tridentate arms of the ligand. The two Cu centers are EPR nonequivalent and noninteracting. The EPR data suggests that one of the Cu ions additionally interacts with one of the tertiary aminonaphthyl donors. In the trinuclear complex the two aminonaphthyl donors bind the third Cu ion. The EPR spectrum of this complex shows the signal for a mononuclear Cu(II) center bound to a tridentate arm, while the remaining two Cu(II) centers are coupled through hydroxo groups. The CD spectrum shows that in the free ligand a severe reduction of the dihedral angle between the naphthyl groups from the strain free range occurs. This conformation is stabilized by ring stacking interactions with the benzimidazole groups. On complex formation this interaction is removed because the benzimidazole groups are involved in metal binding. In the dinuclear Cu complex the conformation of the binaphthyl chromophore probably approaches the strain free range, while in the trinuclear Cu complex a marked flattening of the dihedral angle between the two naphthyl rings occurs. Both complexes are active catalysts in the oxidation of L-/D-Dopa derivatives to quinones. High enantioselectivity is observed in the oxidation of L-/D-Dopa methyl ester catalyzed by the dinuclear Cu complex, which exhibits strong preference for the d enantiomer. The enantioselectivity is largely lost for the trinuclear Cu complex.


A reappraisal of the benefit-risk profile of hydroxyurea in polycythemia vera: A propensity-matched study.
The use of hydroxyurea (HU) as first line therapy in polycythemia vera (PV) has been criticized because no solid demonstration that this drug prevents thrombosis or prolongs survival has been so far produced. Here we present the outcomes of a large cohort of patients with PV included in the European Collaborative Low-dose Aspirin (ECLAP) study. We selected 1,042 patients who, during the follow-up, had received only phlebotomy (PHL) or HU to maintain the hematocrit level < 45%. To assure comparability, we conducted a propensity score matching analysis. The two groups (PHL n = 342 and HU n = 681) were well balanced for the parameters included in the propensity score (overall balance: χ2 = 2.44, P = 0.964). Over a comparable period of follow-up (PHL = 29.9 vs. HU = 34.7 months), we documented an advantage of HU over PHL consistently significant with respect to the incidence of fatal/non-fatal cardiovascular (CV) events (5.8 vs. 3.0 per 100 person-years in PHL vs. HU group, P = 0.002) and myelofibrosis transformation that was only experienced by patients of PHL group. Evolution to acute leukemia was registered in three patients (two in PHL and one in HU group). The excess of mortality and total CV events in the PHL patients was restricted to the high-risk group, and, compared with HU cases, was significant higher in the PHL patients who failed to reach the hematocrit target < 0.45% (P = 0.000). In conclusion, this analysis provides reliable and qualified estimates of the therapeutic profile of HU and PHL treatments for future experimental studies and for the management of PV in clinical practice.


Grading clinical guidelines for the use of transmucosal immediate-release fentanyl products in breakthrough pain.
Pain is a complex symptom that is commonly feared in palliative care owing to its significant effects on patients' quality of life (QoL), and is directly associated with morbidity. More specifically, the management of breakthrough pain (BTP) is particularly important. Opioids play a major part in the management of BTP, and the various transmucosal immediate-release fentanyl (TIRF) products are a common treatment choice. This paper considers the strength of the evidence underlying recommendations regarding the use of TIRF. Failure to consider the quality of evidence in practice can lead to misguided recommendations. Guidelines should therefore be used to inform clinicians of the quality of the underlying evidence and whether recommendations are strong or weak. The GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach is increasingly being adopted worldwide as it provides a system for rating quality of evidence and strength of recommendations that is clear, comprehensive, transparent, and practical. This paper adopts the GRADE approach to assess the strength of recommendations made in a 2011 review by Zeppetella in order to develop guidelines for the use of TIRF. The recommendations include that TIRF products can be considered for first-line treatment and that they should be individualised to patients who are on a background opioid.


LncRNA RSU1P2 contributes to tumorigenesis by acting as a ceRNA against let-7a in cervical cancer cells.
Long non-coding RNAs (lncRNAs) can regulate gene expression at different levels and are widely participate in various physiological and pathological processes. Emerging evidences suggests that a number of differentially expressed lncRNAs are involved in tumorigenesis. However, the function and expression regulation of a vast majority of these unique RNAs is little known. Here, we found that the lncRNA Ras suppressor protein 1 pseudogene 2 (RSU1P2) is upregulateded in cervical cancer tissues and has a tumour-promoting role. We revealed that RSU1P2 acts as a competitive endogenous RNA (ceRNA) through regulating the expression of IGF1R, N-myc and EphA4. The mechanism of this regulation is via competition for the shared microRNA let-7a. This competition promotes the malignant phenotype of cervical carcinoma cells. The transcription factor N-myc forms a positive feedback loop with RSU1P2 by in turn activating its expression, thereby enhancing its oncogenic capacity. Hence, cancer-selective targeting of RSU1P2 could have strong benefits.


Intramolecular [3 + 2]-cycloadditions of azomethine ylides derived from secondary amines via redox-neutral C-H functionalization.
Azomethine ylides are accessed under mild conditions via benzoic acid catalyzed condensations of 1,2,3,4-tetrahydroisoquinolines or tryptolines with aldehydes bearing a pendent dipolarophile. These intermediates undergo intramolecular [3 + 2]-cycloadditions in a highly diastereoselective fashion to form polycyclic amines with four new stereogenic centers. Challenging substrates such as piperidine, morpholine, and thiomorpholine undergo the corresponding reactions at elevated temperatures.


New symmetry of intended curved reaches.
Movement regularities are inherently present in automated goal-directed motions of the primate's arm system. They can provide important signatures of intentional behaviours driven by sensory-motor strategies, but it remains unknown if during motor learning new regularities can be uncovered despite high variability in the temporal dynamics of the hand motions. We investigated the conservation and violation of new movement regularity obtained from the hand motions traced by two untrained monkeys as they learned to reach outwardly towards spatial targets while avoiding obstacles in the dark. The regularity pertains to the transformation from postural to hand paths that aim at visual goals. In length-minimizing curves the area enclosed between the Euclidean straight line and the curve up to its point of maximum curvature is 1/2 of the total area. Similar trend is found if one examines the perimeter. This new movement regularity remained robust to striking changes in arm dynamics that gave rise to changes in the speed of the reach, to changes in the hand path curvature, and to changes in the arm's postural paths. The area and perimeter ratios characterizing the regularity co-varied across repeats of randomly presented targets whenever the transformation from posture to hand paths was compliant with the intended goals. To interpret this conservation and the cases in which the regularity was violated and recovered, we provide a geometric model that characterizes arm-to-hand and hand-to-arm motion paths as length minimizing curves (geodesics) in a non-Euclidean space. Whenever the transformation from one space to the other is distance-metric preserving (isometric) the two symmetric ratios co-vary. Otherwise, the symmetric ratios and their co-variation are violated. As predicted by the model we found empirical evidence for the violation of this movement regularity whenever the intended goals mismatched the actions. This was manifested in unintended curved "after-effect" trajectories executed in the absence of obstacles. In this case, the system was "perturbed" away from the symmetry but after several repeats it recovered its default state. We propose this movement regularity as a sensory-motor transformation invariant of intentional acts.


Histomorphometry of nuclei of proximal convoluted tubules epithelium of kidney of experimental animals after Cladribine (2-CdA) administration.
The area of the section of nuclei of the epithelium cells lining the proximal convoluted tubules of the kidney of white Wistar rats was examined. The animals were given Cladribine (2-CdA) subcutaneously at the dosages of 0.07 mg/kg b.w./24 h for seven days and 0.1 mg/kg b.w./24 h for 6 days in three courses with 5 weeks' break between each. The animals were killed in each instance, 24 hours after the last dose of the drug and 4 weeks after the last dose. The mean area of the section of the cell's nuclei was measured in projection microscope. Results of the examination were counted statistically. In experimental groups I and III the surface areas of the proximal tubules epithelium nuclei cross-sections are smaller than in the control grous. In the experimental groups II and IV the surface areas of the proximal tubules epithelium nuclei cross-sections are bigger than in the control group.


Hypertension, and not sex hormones or insulin resistance affects left ventricular mass in aging men.
Left ventricular hypertrophy (LVH) is an independent risk factor for cardiovascular morbidity and mortality. The aim of the study was to find which factors influence left ventricular mass (LVM) and whether relationships exist between sex hormones: testosterone (T), estradiol (E2), sex hormone binding globulin (SHBG) and insulin resistance (HOMA-IR) and LVM. The study group consisted of 107 males at the age of over 50 years (mean 60.1 +/- 7.0). Positive significant correlations between LVM or left ventricle mass index (LVMI) and hypertension (0.23; p = 0.015 and 0.23; p = 0.019 respectively) as well as between LVM and body weight (0.38; p < 0.001) were observed. LVM and LVMI were higher in hypertensive than in normotensive men (279.9 +/- 82.2 vs. 243.4 +/- 70.3 g, p = 0.015 and 144.6 +/- 41.5 vs. 127.4 +/- 33.1 g/m2, p = 0.019 respectively). Multiple regression analysis showed LVM to be independently associated with hypertension and body weight. For LVMI such correlation was found only with hypertension. No relationships were observed between LVM/LVMI and insulin/insulin resistance.


Trauma in elderly patients: a study of prevalence, comorbidities and gender differences.
Trauma, in geriatric patients, increases with age, and is a leading cause of disability and institutionalization, resulting in morbidity and mortality. The aim of our study was to analyse the prevalence of trauma, the related risk factors, mortality and sex differences in the prevalence in a geriatric population. We observed 4,554 patients (≥65 years) with home injuries or car accidents. Patients were evaluated with ISS (Injury Severity Score) and major trauma with ATLS (Advanced Trauma Life Support). The instrumental investigation was in the first instance, targeted X-Ray or whole-body CT. In over four years of study we treated 4,554 geriatric: 2,809 females and 1,745 Males. When the type of trauma was analysed the most common was head injury, followed by fractures of lower and upper limbs. In our experience hospitalization mainly involved patients over 80. In all patients mortality during assessment was 0.06%. The geriatric patient is often defined as a "frail elderly", for the presence of a greater "injury sensitivity". This is due to the simultaneous presence of comorbidity, progressive loss of full autonomy and exposure to a high risk of traumatic events. Optimal management of the trauma patient can considerable reduce mortality and morbidity. Falls and injuries in geriatric age are more frequent in women than in men. Among typical elder comorbidities, osteoporosis certainly causes a female preponderance in the prevalence of fractures. Our discharge data demonstrate that disability, which requires transfer to health care institutions, has a greater effect on women than men.


Tumor-targeted delivery of siRNA by non-viral vector: safe and effective cancer therapy.
RNA interference technology has been developed as a potential therapeutic agent for many indications, including cancer. Silencing a specific oncogene in tumor cells brings about cell death both in vitro and in vivo. However, there is a great need for powerful delivery strategies to enhance the therapeutic effect of small interfering RNA (siRNA). This review summarizes different signaling pathways inhibited by siRNA and the advantages of targeted siRNA as a delivery system.


Mass Spectrometry as a Quantitative Proteomic Analysis Tool for the Search for Temporal Lobe Epilepsy Biomarkers: A Systematic Review.
Temporal lobe epilepsy (TLE) is the most common form of epilepsy in adults. Tissue reorganization at the site of the epileptogenic focus is accompanied by changes in the expression patterns of protein molecules. The study of mRNA and its corresponding proteins is crucial for understanding the pathogenesis of the disease. Protein expression profiles do not always directly correlate with the levels of their transcripts; therefore, it is protein profiling that is no less important for understanding the molecular mechanisms and biological processes of TLE. The study and annotation of proteins that are statistically significantly different in patients with TLE is an approach to search for biomarkers of this disease, various stages of its development, as well as a method for searching for specific targets for the development of a further therapeutic strategy. When writing a systematic review, the following aggregators of scientific journals were used: MDPI, PubMed, ScienceDirect, Springer, and Web of Science. Scientific articles were searched using the following keywords: "proteomic", "mass-spectrometry", "protein expression", "temporal lobe epilepsy", and "biomarkers". Publications from 2003 to the present have been analyzed. Studies of brain tissues, experimental models of epilepsy, as well as biological fluids, were analyzed. For each of the groups, aberrantly expressed proteins found in various studies were isolated. Most of the studies omitted important characteristics of the studied patients, such as: duration of illness, type and response to therapy, gender, etc. Proteins that overlap across different tissue types and different studies have been highlighted: DPYSL, SYT1, STMN1, APOE, NME1, and others. The most common biological processes for them were the positive regulation of neurofibrillary tangle assembly, the regulation of amyloid fibril formation, lipoprotein catabolic process, the positive regulation of vesicle fusion, the positive regulation of oxidative stress-induced intrinsic apoptotic signaling pathway, removal of superoxide radicals, axon extension, and the regulation of actin filament depolymerization. MS-based proteomic profiling for a relevant study must accept a number of limitations, the most important of which is the need to compare different types of neurological and, in particular, epileptic disorders. Such a criterion could increase the specificity of the search work and, in the future, lead to the discovery of biomarkers for a particular disease.


A world of difference: The fundamental opposition between transhumanist "welfarism" and disability advocacy.
From the standpoint of disability advocacy, further exploration of the concept of well-being stands to be availing. The notion that "welfarism" about disability, which Julian Savulescu and Guy Kahane debuted, qualifies as helpful is encouraged by their claim that welfarism shares important commitments with that advocacy. As becomes clear when they apply their welfarist frame to procreative decisions, endorsing welfarism would, in fact, sharply undermine it. Savulescu and Kahane's Principle of Procreative Beneficence-which reflects transhumanism, or advocacy of radical bioenhancement-morally requires parents to choose the child who will, in all probability, have "the best life." Assuming the emergence of potent biotechnologies, procreative decision-making would be highly standardized, for prospective parents would be morally obliged to maximize select capacities, including intelligence, self-control, and hedonic set-point, in their children. Welfarism, applied to reproduction, is staunchly objectivist about what course is incumbent on decision-makers, giving no credence to first-personal values, aspirations, and experiences. Though this dismissal of individual perspectives applies to everyone, its implications for disability advocacy are especially severe. With that advocacy in view, greater attention to "well-being" should, therefore, be severed from the welfarism of Savulescu and Kahane.


Effects of the CB1R agonist WIN-55,212-2 and the CB1R antagonists SR-141716 and AM-1387: open-field examination in rats.
This study examined the open-field (O-F) effects in rats of the cannabinoid 1 receptor (CB1R) agonist WIN-55,212-2 (WIN; 1 to 5.6 mg/kg) and its interaction with the CB1R antagonist/inverse agonist SR-141716 (1 to 5.6 mg/kg). Additionally, separate studies examined the O-F effects of SR-141716 (1 to 10 mg/kg) and a newly synthesized CB1R selective antagonist/inverse agonist AM-1387 (3 and 10 mg/kg) when these ligands were administered alone. Both antagonists are characterized in vitro by decreased of GTPgammaS binding and increased cAMP accumulation (inverse agonism). WIN dose dependently reduced ambulation (horizontal activity) and rearing (vertical activity); SR-141716 completely (WIN 3 mg/kg) or partially (WIN 5.6 mg/kg) normalized these behaviors. WIN alone resulted in circling and in an increased latency to leave the start area of the O-F, effects blocked by all doses of SR-141716. Both the increased scratching and grooming, associated with SR-141716 administration, were attenuated but not abolished by WIN. SR-141716 alone tended to reduce ambulation (significant at 10 mg/kg) and rearing (non-significant), had no effect on latency, and increased scratching and grooming (both frequency and duration), at doses of 3 mg/kg and up. At the doses examined, AM-1387 had no effect on ambulation, rearing, latency but significantly increased scratching (10 mg/kg); there was also a trend for increased grooming (both frequency and duration). The O-F profile of WIN suggests more similarity with the effects of THC rather than methanandamide (and presumably also anandamide). Intrinsic activity (scratching and grooming) by SR-141716 was re-affirmed and seemed to be associated with administration of AM-1387 as well. AM-1387 was less potent than SR-141716.


Salinity influence on soil microbial respiration rate of wetland in the Yangtze River estuary through changing microbial community.
Estuarine wetland, where freshwater mixes with salt water, comprises different regions (rivers and marine ecosystems) with significantly varying tidal salinities. Two sampling areas, ZXS and JS, were selected to investigate the effect of tidal salinity on soil respiration (SR). ZXS and JS were located in Zhongxia Shoal and Jiangyanan Shoal of Jiuduansha Wetland respectively, with similar elevation and plant species, but significantly different in salinity. The results showed that with almost identical plant biomass, the SR and soil microbial respiration (SMR) of the tidal wetland with lower salinity (JS) were significantly higher than those of the tidal wetland with higher salinity (ZXS) (p<0.05). However, unlike SMR and SR, the difference in the soil microbial biomass (SMB) was not significant (p>0.05) with the SMB of ZXS a little higher than that of JS. The higher SMR and SR of JS may be closely connected to the soil microbial community structures and amount of dominant bacteria. Abundant β- and γ-Proteobacteria and Actinobacteria in JS soil, which have strong heterotrophic metabolic capabilities, could be the main reason for higher SMR and SR, whereas a high number of ε-Proteobacteria in ZXS, some of which have carbon fixation ability, could be responsible for relatively lower carbon output. Path analysis indicated that soil salinity had the maximum negative total influencing coefficient with SMR among the various soil physical and chemical factors, suggesting that higher soil salinity, restricting highly heterotrophic bacteria, is the principle reason for lower SMR and SR in the ZXS.


Alterations in lactoferrin in salivary gland disease.
During the active phase of chronic recurrent parotitis there is a marked elevation in the parotid concentration of lactoferrin (Lf), and iron-binding glycoprotein with antibacterial properties. The Lf concentration decreases during the recovery period, but still remains above normal levels. The changes of Lf in parotitis parallel recent findings in mastitis and pancreatitis. Elevations in Lf were also noted in five of six subjects with Sjögren's disease, but not in subjects with sarcoidosis, diabetes or "dry mouth" without sialographic changes. The source of the Lf has not been determined; it could arise in part from disrupting polymorphonuclear leucocytes and in part from epithelial cells that synthesize Lf in the salivary glands. Inflammatory stimulation of Lf synthesis would suggest a basic protective mechanism in exocrine glands and should be fully explored.


MLC dosimetric characteristics for small field and IMRT applications.
The objective of this work was to measure the performance characteristics of a double-focus multileaf collimator (MLC) for intensity modulated radiation therapy (IMRT), specifically the variation in penumbra and leakage for narrow fields as a function of field position over a 20x27 cm space available for segmented MLC IMRT. Measurements were made with 6 MV x rays through a MLC containing 29 leaf pairs (27 pairs of 1 cm width), and EDR2 film at 10 cm depth in solid water at 100 cm SAD. Films were digitized with 0.17 mm resolution and converted to dose. Interleaf and intraleaf transmission were measured along 11 vertical profile locations. Leaf-end transmission was measured along horizontal profiles for each of 9 different leaf abutments, traveling over a 20 cm range. In-plane penumbra measurements were made through a single leaf retracted, for 7 different leaves. Cross-plane penumbra (leaf-end) measurements were made for all 27 leaf pairs, where the 1 cm field width was placed in 11 different off-axis positions (20 cm range). Interleaf leakage (range 1.0%-1.5%), intraleaf transmission (range 0.6%-0.8%), and leaf-end transmission (range 0.8%-2.7%) were consistent for all leaf pairs at a given abutment position. The penumbra for these 1-cm-wide fields was measured to be 0.36 cm+/-0.03 cm for 99% of the measurements. In conclusion, the penumbra and leakage of the double-focus MLC were remarkably consistent for the range of leaf positions studied, producing dosimetric characteristics that are well suited for IMRT segments where opposing leaf pairs are often separated by 10 mm or less.


Early anti-inflammatory intervention ameliorates axial disease in the proteoglycan-induced spondylitis mouse model of ankylosing spondylitis.
Ankylosing spondylitis (AS) is characterised by immune-mediated arthritis and osteoproliferation, ultimately leading to joint ankylosis. Whether inflammation is necessary for osteoproliferation is controversial, fuelled by the unclear efficacy of anti-inflammatory treatments on radiographic progression. In proteoglycan-induced spondylitis (PGISp), a mouse model of AS, inflammation is the prerequisite for osteoproliferation as osteoproliferation was only observed following inflammation-driven intervertebral disc (IVD) destruction. We hypothesised that early intervention with a potent anti-inflammatory therapy would protect IVD integrity and consequently alter disease progression. PGISp mice received vehicle or a combination of etanercept (ETN) plus prednisolone (PRD) therapy for 2 or 6 weeks initiated at an early disease stage. Peripheral arthritis was scored longitudinally. Spinal disease was assessed using a semi-quantitative histological scoring regimen including inflammation, joint destruction and excessive tissue formation. ETN + PRD therapy significantly delayed the onset of peripheral arthritis. IVD integrity was significantly protected when treatment was commenced in early disease. Six-weeks of treatment resulted in trends towards reductions in intervertebral joint damage and excessive tissue formation. IVD score distribution was dichotomized, likely reflecting the extent of axial disease at initiation of therapy. In the sub-group of mice with high IVD destruction scores, ETN + PRD treatment significantly reduced IVD destruction severity, inflammation and bone erosion and reduced cartilage damage and excessive tissue formation. Early intervention with anti-inflammatory treatment not only improved inflammatory symptoms but also ameliorated structural damage of spine in PGISp mice. This preclinical observation suggests that early anti-inflammatory intervention may slow radiographic progression in AS patients.


Mechanisms for attenuation in cancellous-bone-mimicking phantoms.
Broadband ultrasound attenuation (BUA) in cancellous bone is useful for prediction of osteoporotic fracture risk, but its causes are not well understood. To investigate attenuation mechanisms, 9 cancellous-bone-mimicking phantoms containing nylon filaments (simulating bone trabeculae) embedded within soft-tissue-mimicking fluid (simulating marrow) were interrogated. The measurements of frequency-dependent attenuation coefficient had 3 separable components: 1) a linear (with frequency) component attributable to absorption in the soft-tissue-mimicking fluid, 2) a quasilinear (with frequency) component, which may include absorption in and longitudinal-shear mode conversion by the nylon filaments, and 3) a nonlinear (with frequency) component, which may be attributable to longitudinal-longitudinal scattering by the nylon filaments. The slope of total linear (with frequency) attenuation coefficient (sum of components #1 and #2) versus frequency was found to increase linearly with volume fraction, consistent with reported measurements on cancellous bone. Backscatter coefficient measurements in the 9 phantoms supported the claim that the nonlinear (with frequency) component of attenuation coefficient (component #3) was closely associated with longitudinal-longitudinal scattering. This work represents the first experimental separation of these 3 components of attenuation in cancellous bone-mimicking phantoms.


Rna synthesis and processing during cytodifferentiation in fetal rat pancreas.
In fetal rat pancreas cytodifferentiation occurs between day 14 and day 20 of gestation and is accompanied by an exponential increase in the cellular accumulation of tissue specific proteins and an elaboration of the cellular organelles associated with their synthesis and secretion. Evaluation of RNA synthesis by [3H] uridine incorporation into trichloroacetic acid precipitable material showed that during this period the apparent rate of RNA synthesis increased 7.5 fold from 2 x 10(3) dpm/micrograms DNA/h on day 15 to 1.5 x 10(4) dpm/micrograms DNA/h on day 19; [3H] leucine uptake showed that the rate of protein synthesis increased about the same extent with the major difference being that the maximum rate of protein synthesis occurred on day 19, one day after the maximum rate of RNA synthesis. The soluble pyrimidine nucleotide pools decreased from 122 pmol/micrograms DNA on day 14 to 15 pmol/micrograms DNA on day 16 followed by an increase to 104 pmol/micrograms DNA on day 19; the purine nucleotide pools decreased from 367 pmol/micrograms DNA on day 14 to 286 pmol/micrograms DNA on day 16 and then increased to 635 pmol/micrograms DNA on day 19. These values roughly paralleled the transitions observed in the rates of RNA and protein synthesis. Agarose-acrylamide slab gel electrophoresis showed an increase in RNA synthesis and an increase in ribosomal RNA synthesis and processing with cytodifferentiation.


Low rate of genotypic HIV-1 drug-resistant strains in the Senegalese government initiative of access to antiretroviral therapy.
To monitor the prevalence of antiretroviral (ARV)-resistant HIV-1 viruses, and the genotypic mutations in patients enrolled in the Senegalese initiative for access to antiretroviral treatment (ART). A total of 80 patients with a virological follow-up of at least 6 months were selected, 68 were ART-naive and 12 ART-experienced. Genotypic resistance to ARV was studied at baseline for a random subset of patients and at each rebound in plasma viral load during ART, by sequencing the protease and reverse transcriptase genes. At baseline, 66 patients received highly active antiretroviral therapy (HAART) [2 nucleoside reverse transcriptase inhibitors (NRTIs) +1 protease inhibitor (PI) (n = 64) or 2 NRTIs + 1 non-nucleoside reverse transcriptase inhibitor (NNRTI) (n = 2)] and 14 patients (17.5%) started with a dual therapy because of ongoing antitubercular therapy or efficient previous bitherapy for the ART-experienced patients. The emergence of drug-resistant viruses (n = 13) during follow-up was more frequent in ART-experienced patients than in ART-naive patients, 41.7 versus 11.8%, resistant viruses emerged at comparable follow-up periods, a median of 17.8 and 18.3 months, respectively. In patients receiving zidovudine and lamivudine in their drug regimen, resistance to lamivudine was more frequent than to zidovudine. Two of the three patients, with viruses resistant to PIs, acquired mutations associated with cross-resistance. Strikingly, five (39%) of the 13 patients developed resistances to drugs that they had never received (n = 3) or that they received 18 or 36 months ago (n = 2). Didanosine/stavudine pressure had selected zidovudine-resistant viruses in four patients, and indinavir had selected a nelfinavir-resistant virus in one patient. In contrast to other reports from developing countries where patients had received ARVs in an uncontrolled manner, our study showed that implementation of HAART together with good clinical, biological and logistical monitoring can reduce the emergence of resistant strains in Africa.


Hybrid laser/broadband EMAT ultrasonic system for characterizing cracks in metals.
Detection and characterization of defects in metal parts in industrial and commercial settings has typically been carried out by nondestructive ultrasonic inspection systems. Correct measurement of crack size is critical for lifetime prediction inspections. Normally, measurements are made based on far-field ultrasonic diffraction models and time-of-flight reflection signals making accurate measurements for parts less than approximately 25 mm in thickness impossible. In this work a hybrid noncontacting laser generation/broadband electromagnetic acoustic transducer (EMAT) detection system is used to characterize ideal cracks in aluminum in which the far-field condition for ultrasonic diffraction cannot be met. Time domain signals show that diffracted energy is measured in the geometrical shadow zone of the crack. Fourier transform methods are used to show that the frequency content of the diffracted signals is different than those from the waves that do not interact with the crack. Crack size measurements are made by using the frequency content of the ultrasonic signal rather than time-of-flight information.


[Determination of duration of action of beta blockers with Holter-ECG registration].
Duration of Action of Betaadrenergic Blockers Determined with Holter-ECG in Healthy Volunteers In phase I, the duration of action of betaadrenergic blockers is usually determined from the reduction of exercise induced tachycardia. In this randomized placebocontrolled doubleblind trial, however, ambulatory 24-h heart rate monitoring was used in 12 healthy volunteers to evaluate the duration of action of the new cardioselective and vasodilating betaadrenergic blocker ridazolol (CAS413). After the control periods as well as after prospectively defined hours the following mean values of heart rate were obtained: Ridazolol: Control 65.2, 12 h 69.6, 16 h 64.9, 24 h 74.0 beasts/min, placebo: Control 64.8, 12 h 78.5, 16 h 69.7, 24 h 73.5 beats/min. Differences after 12 h were statistically significant and would have been significant after 16 h with more volunteers. Additional explorative analysis with adjustment of significance levels for multiple analysis resulted in significant effects from 2 to 14 h. It was not useful, however, to calculate the time of maximal and half-maximal effects because of the large individual variation. Holter-monitoring of spontaneous heart rate in volunteers provides a rapid orientation on the duration of action of betaadrenergic blockers. The method allows to fix prospectively reasonable times of evaluation in efficacy trials in patients with coronary artery disease.


The influence of amine/amide versus bisamide coordination in nickel superoxide dismutase.
Nickel superoxide dismutase (NiSOD) is a mononuclear nickel-containing metalloenzyme that catalyzes the disproportionation of superoxide by cycling between NiII and NiIII oxidation states. In the reduced NiII oxidation state, the metal center is ligated by two cysteinate sulfurs, one amide nitrogen, and one amine nitrogen (from the N-terminus), while in the oxidized NiIII state, an imidazole nitrogen coordinates to the metal center. Herein, we expand on a previous report in which we described a functional metallopeptide-based NiSOD model compound [NiII(SODM1)] (SODM1 = H2N-HCDLPCGVYDPA-COOH) by exploring how acylation of the N-terminus (producing [NiII(SODM1-Ac)]) influences the properties of the metallopeptide. Titration results, GPC data, and mass-spectrometry data demonstrate that NiII coordinates to SODM1-Ac in a 1:1 ratio, while variable pH studies show that NiII coordination is strong at a pH of 7.5 and above but not observed below a pH of 6.2. This is higher than [NiII(SODM1)] by approximately 1.0 pH unit consistent with bisamide ligation. Ni K-edge XAS demonstrates that the NiII center is coordinated in a square-planar NiN2S2 coordination environment with Ni-N distances of 1.846(4) A and Ni-S distances of 2.174(3) A. Comparison of the electronic absorption and CD spectrum of [NiII(SODM1)] versus [NiII(SODM1-Ac)] in conjunction with time-dependent DFT calculations suggests a decrease in Ni covalency in the acylated versus unacylated metallopeptide. This decrease in covalency was also supported by DFT calculations and Ni L-edge XAS. [NiII(SODM1-Ac)] has a quasireversible NiII/NiIII redox couple of 0.49(1) V vs Ag/AgCl, which represents a -0.2 V shift compared with [NiII(SODM1)], while the peak separation suggests a change in the coordination environment upon oxidation (i.e., axial imidazole ligation). Using the xanthine/xanthine oxidase assay, we determine that [NiII(SODM1-Ac)] is less active than [NiII(SODM1)] by over 2 orders of magnitude (IC50 = 3(1) x 10-5 vs 2(1) x 10-7 M). Possible reasons for the decrease in activity are discussed.


PROPOSAL AND APPLICATION OF A NOVEL DISSEMINATED INTRAVASCULAR COAGULATION SCORING SYSTEM IN THE FLORIDA MANATEE (TRICHECHUS MANATUS LATIROSTRIS).
Disseminated intravascular coagulopathy (DIC) is an acquired disorder of hemostasis resulting in activation of the coagulation and fibrinolytic pathways. It is reported secondarily to multiple disease processes and can be associated with increased mortality. Previous research at Tampa's Lowry Park Zoo (LPZ) demonstrated that Florida manatees ( Trichechus manatus latirostris) with cold stress syndrome (CSS) demonstrated thromboembolic disease. The object of this retrospective study was to establish the presence and clinical relevance of DIC in Florida manatees admitted to LPZ for rehabilitation from 07 March 2010 to 15 August 2015. A coagulation panel, including prothrombin time, partial thromboplastin time, platelet count, fibrinogen level, and D-dimer level was used to diagnose DIC. There were 100 cases identified in the study period: 35 trauma, 43 CSS, 17 secondary to harmful algae blooms (HAB), and five miscellaneous. Manatees with CSS had the highest incidence of DIC with 24 of 43 cases (56%) affected, followed by trauma with 18 of 35 cases (52%) affected. None of the manatees with HAB were found to have DIC. Manatees that developed DIC during rehabilitation or when DIC progressed did not survive. Due to the clinical implications of DIC, identifying its presence and recognizing its severity could improve clinical outcomes by enabling more intensive treatment protocols.


Structure of the hematopoietic tyrosine phosphatase (HePTP) catalytic domain: structure of a KIM phosphatase with phosphate bound at the active site.
Hematopoietic tyrosine phosphatase (HePTP) is a 38kDa class I non-receptor protein tyrosine phosphatase (PTP) that is strongly expressed in T cells. It is composed of a C-terminal classical PTP domain (residues 44-339) and a short N-terminal extension (residues 1-43) that functions to direct HePTP to its physiological substrates. Moreover, HePTP is a member of a recently identified family of PTPs that has a major role in regulating the activity and translocation of the MAP kinases Erk and p38. HePTP binds Erk and p38 via a short, highly conserved motif in its N terminus, termed the kinase interaction motif (KIM). Association of HePTP with Erk via the KIM results in an unusual, reciprocal interaction between the two proteins. First, Erk phosphorylates HePTP at residues Thr45 and Ser72. Second, HePTP dephosphorylates Erk at PTyr185. In order to gain further insight into the interaction of HePTP with Erk, we determined the structure of the PTP catalytic domain of HePTP, residues 44-339. The HePTP catalytic phosphatase domain displays the classical PTP1B fold and superimposes well with PTP-SL, the first KIM-containing phosphatase solved to high resolution. In contrast to the PTP-SL structure, however, HePTP crystallized with a well-ordered phosphate ion bound at the active site. This resulted in the closure of the catalytically important WPD loop, and thus, HePTP represents the first KIM-containing phosphatase solved in the closed conformation. Finally, using this structure of the HePTP catalytic domain, we show that both the phosphorylation of HePTP at Thr45 and Ser72 by Erk2 and the dephosphorylation of Erk2 at Tyr185 by HePTP require significant conformational changes in both proteins.


Short form of the developmental behaviour checklist.
A 24-item short form of the 96-item Developmental Behaviour Checklist was developed to provide a brief measure of Total Behaviour Problem Score for research purposes. The short form Developmental Behaviour Checklist (DBC-P24) was chosen for low bias and high precision from among 100 randomly selected item sets. The DBC-P24 was developed from epidemiological data in the first three waves of the Australian Child to Adult Development study, and cross validated for groups with autism, fragile X, Prader-Willi, and Williams in this longitudinal study and in cross sectional Dutch, English, and Finnish samples of young people with intellectual disability. The DBC-P24 has low bias and high precision in cross-validation samples and achieves high sensitivity and specificity to full DBC-P based caseness decisions.


Supracrestal gingival tissue measurement in normal periodontium: a human histometric study.
Twenty-four teeth were extracted en bloc with the marginal periodontal structures and processed for histologic purposes. Measurements were taken from the top of the gingival margin to the apical limit of the junctional epithelium (GM-JE), from the apical limit of the junctional epithelium to the top of the alveolar bone crest (JE-AB), and from the top of the gingival margin to the top of the alveolar bone crest (GM-AB). Data were histometrically analyzed. This first clinical human study demonstrated mean measurements of 1.58 ± 0.41 mm for GM-JE, 1.18 ± 0.42 mm for JE-AB, and 2.75 ± 0.59 mm for GM-AB.


Malignancy risk in Australian rheumatoid arthritis patients treated with anti-tumour necrosis factor therapy: analysis of the Australian Rheumatology Association Database (ARAD) prospective cohort study.
Malignancy risk with tumour necrosis factor inhibitor (TNFi) therapy remains unclear. Our primary aim was to assess malignancy risk with TNFi therapy in a cohort of Australian patients with rheumatoid arthritis (RA). We also assessed risk in a biologic-naïve group. Demographic data of all RA patients enrolled in the Australian Rheumatology Association Database before 25 October 2010 were matched to national cancer records in July 2010 (linkage complete to 2007). Verified self-reported malignancies occurring between 1 January 2008 and 25 October 2010 were also included in the analysis. Standardised incidence ratios (SIRs) were used to compare malignancy incidence in biologic-naïve and TNFi-exposed ARAD participants to the general population using site-, age- and sex-specific rates by calendar year. Rate ratios (RRs) were used to compare malignancy incidence in TNFi-exposed participants to biologic-naïve RA patients, and a composite RA cohort that included pre-TNFi person years, both adjusted for age, gender, smoking, methotrexate use and prior malignancy. Forty-four malignancies were reported after 5752 person-years in the TNFi-exposed group (N = 2145) and 32 malignancies were reported after 1682 person-years in the biologic-naïve group (N = 803). No overall increased risk of malignancy in TNFi-treated RA patients was found when compared with the general population or with biologic-naïve RA patients. Compared to the biologic naïve group, without the inclusion of pre-TNFi years in the comparator group, the relative risk of female breast cancer was reduced in TNFi-treated patients (RR 0.17 (95 % CI 0.03 to 0.95)). It was no longer significant when adding pre-TNFi years in the comparator group. The risk of melanoma was increased for both biologic naïve and TNFi-treated patients when compared with the general population (SIR 2.72 (95 % CI 1.13 to 6.53) and SIR 2.03 (95 % CI 1.09 to 3.78) respectively). The relative risk of melanoma was not increased in the TNFi-exposed group compared with biologic naïve patients (RR 0.54, 95 % CI 0.12, 2.40). Inclusion of pre-TNFi person years in the comparator group did not change these results. Malignancy incidence was low in this RA cohort and biologic exposure did not increase the risk of malignancy. Melanoma risk was increased in both TNFi-treated and biologic-naïve RA patients compared with the general population suggesting that RA status, and possibly methotrexate exposure, may be responsible.


Systematic review of the top 10 ranked spine articles in the last 10 years [2011-2021].
Spine-related research continues to evolve rapidly and in the paradigm of increasing data, evidence-based practice becomes imperative. Citation-based rankings are thus critical in allowing clinicians to quickly ascertain the importance and value of a study. The purpose of this article is to report on the 10 most cited articles in the field of spine surgery over the last 10 years to provide an insight into the direction of research and clinical endeavors. Google Scholar was searched (1st April 2021) using an algorithm that sorts all cited spine surgery publications based on the number of citations per year. The top 10 most cited articles were identified. Information including journal, publication title, published year, subspecialty, and purpose of the study were compiled. The top 10 publications ranged from 471 to 66 citations, with yearly citations ranging from 67 to 14. Eight articles directly related to lumbar fusion, 2 related to 3D Printing in spinal surgery, and one article on robotic surgery. There were 4 retrospective studies, 1 randomized controlled trial (RCT), and 2 systematic reviews. 3 of the papers related to decision making in surgery, 4 on outcomes of surgery, and 3 on innovations in surgery. The journal that appeared most frequently in the top 10 list was the Journal of Spine Surgery. Novel surgical approaches or management strategies are almost always a manifestation of advancements in clinical and basic science research. Algorithm-based identification of highly cited articles provides an effective and prompt avenue for evidence-based medicine. Our ranking found a predominance of publications related to lumbar spinal fusion. Several articles in the top 10 provide an in-depth discussion on novel surgical techniques and technologies that define the current epoch of innovations in spine surgery.


The C962R ORF of African Swine Fever Strain Georgia Is Non-Essential and Not Required for Virulence in Swine.
African swine fever virus (ASFV) is the causative agent of the African swine fever (ASF) epizootic currently affecting pigs throughout Eurasia, causing significant economic losses in the swine industry. The virus genome encodes for more than 160 genes, of which only a few have been studied in detail. Here we describe the previously uncharacterized ASFV open reading frame (ORF) C962R, a gene encoding for a putative NTPase. RNA transcription studies using infected swine macrophages demonstrate that the C962R gene is translated as a late virus protein. A recombinant ASFV lacking the C962R gene (ASFV-G-ΔC962R) demonstrates in vivo that the C962R gene is non-essential, since ASFV-G-ΔC962R has similar replication kinetics in primary swine macrophage cell cultures when compared to parental highly virulent field isolate Georgia2007 (ASFV-G). Experimental infection of domestic pigs with ASFV-G-ΔC962R produced a clinical disease similar to that caused by the parental ASFV-G, confirming that deletion of the C962R gene from the ASFV genome does not impact virulence.


Modulation of steroidogenesis by vitamin D3 in granulosa cells of the mouse model of polycystic ovarian syndrome.
Polycystic ovarian syndrome (PCOS) is the most common endocrine disorder of women of reproductive age characterized by polycystic ovarian morphology, anovulation or oligomenorrhea, and hyperandrogenism. It is shown that disruption in the steroidogenesis pathway caused by excess androgen in PCOS is a critical element of abnormal folliculogenesis and failure in dominant follicle selection. Vitamin D plays an important role in the regulation of ovulatory dysfunction and can influence genes involved in steroidogenesis in granulosa cells. In the present study, we investigated the effects of vitamin D3 on steroidogenic enzyme expression and activities in granulosa cell using a PCOS mouse model. In our study, the PCOS mouse model was developed by the injection of dehydroepiandrosterone (DHEA) for 20 days. The mRNA and protein expression levels of genes involved in steroidogenesis in granulosa cells were compared between polycystic and normal ovaries using real-time PCR and Western blotting assays. Granulosa cells of DHEA-induced PCOS mice were then cultured with and without vitamin D3 and mRNA and protein expression levels of steroidogenic enzymes and serum 17beta-estradiol and progesterone levels were investigated using qRT-PCR, western blot, and radioimmunoassay, respectively. Steroidogenic enzymes including Cyp11a1, StAR, Cyp19a1, and 3β-HSD were upregulated in granulosa cells of PCOS mice when compared to normal mice. Treatment with vitamin D3 decreased mRNA and protein expression levels of steroidogenic enzymes in cultured granulosa cells. Vitamin D3 also decreased aromatase and 3β-HSD activity that leads to decreased 17beta-estradiol and progesterone release. This study suggests that vitamin D3 could modulate the steroidogenesis pathway in granulosa cells of PCOS mice that may lead to improving follicular development and maturation. This is a step towards a possible conceivable treatment for PCOS. AMHR-II: anti-müllerian hormone receptor-II; 3β-HSD: 3β-hydroxysteroid dehydrogenase; Cyp11a1: Cytochrome P450 Family 11 Subfamily A Member 1; Cyp19a1: cytochrome P450 aromatase; DHEA: dehydroepiandrosterone; FSH: follicle stimulating hormone; FSHR: follicle stimulating hormone receptor; IVF: in vitro fertilization; 25OHD: 25-hydroxy vitamin D; OHSS: ovarian hyperstimulation syndrome; PCOS: polycystic ovarian syndrome; P450scc: P450 side-chain cleavage enzyme; StAR: steroidogenic acute regulatory protein; VDRs: vitamin D receptors.


Modification and enhanced anti-inflammatory activity by Bifidobacterial fermentation of an exopolysaccharide from a medicinal fungus Cs-HK1.
The exopolysaccharide (EPS) from the mycelial fermentation of a medicinal fungus Cordyceps sinensis Cs-HK1 had shown significant anti-inflammatory activity previously, and EPS-LM was a highly active fraction with a relatively low molecular weight (MW) isolated from the Cs-HK1 EPS. This study was to assess the effects of Bifidobacterial fermentation in anaerobic conditions on the molecular properties and anti-inflammatory activity of EPS-LM. In both Bifidobacterial cultures (B. breve and B. longum), EPS-LM was fractionally consumed as a carbon source, increasing the bacterial growth and acetic acid production. Analytical results from the fermentation digesta (supernatant) suggested that EPS-LM was partially degraded to lower molecular weight (MW) products with modified structures during the Bifidobacterial fermentation. More interestingly, the higher MW digesta fraction containing the partially degraded EPS-LM showed even stronger inhibiting activity than the original EPS-LM on the LPS-induced pro-inflammatory responses in THP-1 cell culture, including NF-κB activation, release of NO, TNF-α and IL-8. The study has shown that the fermentation by selected Bifidobacterial strains is effective to modify natural polysaccharides with enhanced bioactivities.


Canadian opinions on publicly financed dental care.
Inequalities in oral health and care are long recognized in Canada, with public health environments increasingly focusing on issues of equity and access to care. How does Canada publicly insure for diseases that are largely preventable, minimally experienced by the majority, but that still cause tremendous suffering among the socially marginalized? We consider this dynamic by asking Canadians their opinions on publicly financed dental care. Data were collected from 1,006 Canadian adults through a telephone interview survey using random digit dialling and computer-assisted telephone interview technology. Simple descriptive and bivariate analyses were undertaken to assess relationships among variables, with logistic regression odds ratios calculated for significant relations. Canadians support the idea of universal coverage for dental care, also recognizing the need for care to specific groups. Generally preferring to access public care through the private sector, Canadians support the idea of opting out, and expect those who access such care to financially contribute at point of service. Support for publicly financed dental care is indicative of a general support for a basic right to health care. Within the limits of economy, the distribution of oral disease, and Canadian values on health, the challenge remains to define what we think is equitable within this sector of the health care system. This question is ultimately unanswerable through any survey or statistical means, and must, to become relevant, be openly promoted and debated in the social arena, engaging Canadians and their sense of individual and social responsibility.


Acute toxicity levels and ethological responses of Channa striatus to fertilizer industrial wastewater.
The present paper deals with the toxicity of fertilizer's industrial wastewater on snake head fish Channa striatus (Bloch) previously named as Ophiocephalus sp., at different concentrations viz., 20, 40, 60, 80 and 100 percent on the behavioural changes and mortality. The exposed fish showed hyperactivity viz., jumping, operculum movement, distance travelling, somersaulting at higher concentration such as 60, 80, and 100 percent within 48 hr. At lower concentrations such as 20 and 40 percent exposed fish showed hyperactivities viz., linear movement and eye movement within 48 hr. The LC50 values of industrial wastewater were also determined viz. 89, 75, 70 and 69 percent at different duration of exposure time i.e. 48, 72, 96 and 120 hr respectively. The obtained data revealed that LC50 value decreased with increase of exposure.


Calculated initial parenteral treatment of bacterial infections: Sepsis.
This is the eleventh chapter of the guideline "Calculated initial parenteral treatment of bacterial infections in adults - update 2018" in the 2nd updated version. The German guideline by the Paul-Ehrlich-Gesellschaft für Chemotherapie e.V. (PEG) has been translated to address an international audience. Sepsis, defined as a life threatening organ dysfunction caused by a misregulated host response to an infection, is the third leading cause of death in Germany with a lethality rate of 30% to over 50%. An early, effective antimicrobial therapy is, next to infectious source control, the most important causal treatment option. It should be complemented by the mainly supportive measures of general intensive care therapy. Prior antimicrobial therapy, the patient's medical history (e.g. risk factors for multiresistant agents) and small-scale epidemiology are to be considered as part of the therapeutic and practical decisions. A modification of the often needed broad initial calculated combination therapy is desirable. In the future, prompt measurements of plasma concentrations of antiinfectives, especially for the sepsis patient with diverse and partly conflicting pathophysiological changes, will have great importance regarding efficacy, toxicity and resistance development. In order to apply those complex strategies in clinical routine, there is a requirement for a strong interdisciplinary collaboration between the intensive care unit, clinical infectiology, microbiology, and clinical pharmacology, ideally in the framework of a functional antimicrobial stewardship program.


Pre-retirement job and the work-to-retirement occupational transition process in Australia: A review.
The transition from work to retirement is a complex process and unique experience with a relationship existing between work and retirement with implications for health in later life. This review explored the relationship between pre-retirement job and participation in the work-to-retirement transition process in Australia by exploring: (i) factors influencing retirement in relation to pre-retirement job; (ii) how jobs are classified; (iii) the effect of pre-retirement job (based on categories) on this occupational transition; and (iv) the potential role for occupational therapy in this occupational transition. An integrative literature review was completed. PRISMA guidelines were used. Study designs were analysed for methodological quality using the National Health and Medical Research Council levels of evidence. Thematic analysis determined retirement factors which were used to compare differences between jobs. This review included 15 papers. There were two Level III-2, one Level III-3 and 13 Level IV studies. Factors influencing retirement related to the stages of work, preparation, transition and retired. White collar and blue collar was the most common job classification system. Although white collar and blue collar worker definitions utilised were inconsistent, differences between the two groups were still determined in all stages. Differences in the work-to-retirement transition process, based on pre-retirement job, are evident. Understanding differences by job groupings may assist occupational therapists to understand individualised needs during this occupational transition and subsequent tailoring of interventions (both individual and group based) to enable engagement in meaningful occupation in the work-to-retirement occupational transition to effect active healthy ageing.


Cytochemical Localization of Polyphenol Oxidase Activity in K2-Bodies of Saprolegnia ferax Secondary Zoospores.
Zoospores of the oomycete Saprolegnia ferax release adhesive material from K-bodies at the onset of attachment to substrates. To understand more fully how K-bodies function in adhesion, enzyme activity was investigated cytochemically in secondary zoospores. Presence of catalase, a marker enzyme for microbodies, was explored in the diaminobenzidine (DAB) reaction. Although pH 9.2 DAB-staining characteristic of catalase activity was detected in the granular matrix regions of K-bodies, reaction controls indicated that the reaction was due to oxidative enzyme activity other than catalase. Because polyphenol oxidase (PPO) is another metal-containing enzyme capable of oxidizing DAB, activity of this enzyme was tested with a more specific substrate, dihydroxyphenylalanine (DOPA). In the DOPA procedure, reaction product was exclusively localized within K-bodies, indicating the presence of PPO. Results with three methods of reaction controls (elimination of substrate, addition of a PPO enzyme inhibitor, and heat-inactivation of enzymes) all supported the presence of PPO in K-bodies. This study highlights potential roles for K-body PPO in stabilization of adhesion bodies by: cross-linking matrix phenolic proteins or glycoproteins as K-bodies discharge adhesives onto substrates, or polymerizing phenolics protective against microbial attacks of the adhesion pad.


Controlled Release Oral Delivery of Apigenin Containing Pellets with Antioxidant Activity.
Drug delivery of phytochemicals has gained interest recently due to their remarkable health effects. Apigenin, a plant flavonoid, has antioxidant, anti-inflammatory and anticancer activities but its delivery is challenging. It could be absorbed through the whole intestine, however, it has poor bioavailability due to its low aqueous solubility. In Europe, the daily intake was estimated to be as low as 3 ± 1 mg. Pellets offer several advantages such as improved bioavailability and various resultant drug release profiles can be obtained by simply mixing pellets with different coatings. The objective of our study was to develop a carrier system containing 20 mg apigenin thus enhancing intake and to offer reduction of oxidative stress which can cause inflammation in the intestine. The apigenin powder was dispersed in aqueous solution of binding material and layered onto the inert cores in a fluidized bed apparatus. The layered cores were further coated with enteric polymers and the process parameters were optimized. The prepared pellets met with the requirements and have good physical characteristic. 10% (w/w) Eudragit® L was suitable for enteric coating with a complete release at pH 6.8 within 1 hour. 15% (w/w) Eudragit® FS coating ensured acid resistance ability and colonic delivery. The therapeutic efficiency was confirmed with antioxidant activity measurement by using DPPH* assay. Enteric coated spheres allow targeted delivery into the intestine and colon thus reaching the main absorption site. Pellets were proved to be an optimal delivery system for apigenin thus providing enhanced apigenin intake.


Short-Axis PET Image Quality Improvement by Attention CycleGAN Using Total-Body PET.
The quality of positron emission tomography (PET) imaging is positively correlated with scanner sensitivity, which is closely related to the axial field of view (FOV). Conventional short-axis PET scanners (200-350 mm FOV) reduce the imaging quality during fast scanning (2-3 minutes) due to the limitation of FOV, which reduce the reliability of diagnosis. To overcome hardware limitations and improve the image quality of short-axis PET scanners, we propose a supervised deep learning model, CycleAGAN, which is based on a cycle-consistent adversarial network (CycleGAN). We introduced the attention mechanism into the generator and focus on channel and spatial representative features and supervised learning using pairs of data to maintain the spatial consistency of the generated images with the ground truth. The imaging information of 386 patients from Henan Provincial People's Hospital was prospectively included as the dataset in this study. The training data come from the total-body PET scanner uEXPLORER. The proposed CycleAGAN is compared with traditional gray-level-based methods and learning-based methods. The results confirm that CycleAGAN achieved the best results on SSIM and NRMSE and achieved the closest distribution to ground truth in expert rating. The proposed method is not only able to improve the image quality of PET scanners with 320 mm FOV but also achieved good results on shorter FOV scanners. Patients and radiologists can benefit from the computer-aided diagnosis (CAD) system integrated with CycleAGAN.


Serum immunoglobulin G responses to various Actinobacillus actinomycetemcomitans serotypes in a young ethnographically heterogeneous periodontitis patient group.
Sera from young patients with periodontal diseases have been shown to often contain highly elevated antibody levels to Actinobacillus actinomycetemcomitans, in particular serotype b. Such responses were reportedly predominated by antibodies of the immunoglobulin G2 (IgG2) subclass. The aim of this study was to investigate an ethnically diverse group of 14 early-onset periodontitis and 15 rapidly progressive periodontitis patients for the occurrence of elevated antibody titers against the five known A. actinomycetemcomitans serotypes, and to compare the patient's IgG subclass response profiles. Enzyme-linked immunosorbent assays were used to measure both total IgG and subclass specific IgG titers. Twenty-four subjects had markedly elevate total IgG levels against at least one serotype. The frequencies of high responses against serotypes a, b, c, d and e were 7, 11, 6, 4, and 4, respectively. Elevated antibody responses were predominated by IgG2, regardless of the serotype to which the response was directed. The serotype specificity of the host responses was further investigated by competitive binding studies with serotype-specific monoclonal antibodies. Twelve sera were found to contain antibodies capable of strongly inhibit the binding of monoclonal antibodies against a single serotype; four other sera had antibodies against epitopes of two, and one serum against those of three serotypes. The findings document broad serotype diversity in an ethnically heterogeneous group of patients and indicate that strong antibody responses to A. actinomycetemcomitans are predominated by IgG2 regardless of the serotype of the infective agent.