[Analysis of clinical effectiveness and risk factors for complication of percutaneous nephrolototripsia in patients with a solitary kidney].
Management of patients with large and staghorn stones of a solitary kidney is widely debated among urologists and has not been sufficiently investigated, which determined the relevance of this study. The study comprised 80 patients with large (>20 mm) and staghorn stones of an anatomically or functionally solitary kidney. Of them, 58 patients underwent percutaneous nephrolithotripsy (PNL), and 22 had open surgery. The criterion of the treatment effectiveness was the complete stone clearance or small residual fragments sized less than 3 mm. The safety criterion was the absence of intra- and postoperative complications, according to Clavien-Dindo grading system. The study analyzed the following factors influencing the effectiveness and safety of PNL: the number of accesses; nephroscope diameter; use of a nephroscope sheath; type of lithotripter; size, density, type and composition of the stone. Percutaneous nephrolithotripsy demonstrated statistically significantly better safety results compared with open surgery with comparable effectiveness. Long-term stone recurrence rate after PNL and open surgery was 10.4 and 18.2%, respectively. PNL resulted in a statistically significant improvement in the kidney function while it worsened after open surgery. The effectiveness of PNL depends on the stone type and size and the kind of lithotripter. It was 7.5 times greater for a large stone than for staghorn calculi and 4.6 times higher for stones sized less or equal 45 mm than for those sized > 45 mm. Ultrasonic lithotripter was 2.2 times more effective than another type of lithotripter. The safety of PNL depends on the nephroscope diameter, of a sheath, the number of accesses, the type of lithotripter and the type of stone. Using a 24-Ch nephroscope was 3.6 times safer than that with a diameter greater than 24-Ch; not using a sheath was 3.2 times safer than using it; one access was 3 times safer than at multiple ones; using an ultrasound lithotripter was 2.7 times safer than with another type of lithotripter; treating a large stone was 2.1 times safer than a staghorn stone. The study findings can be used to optimize the treatment of patients with large and staghorn stones of a solitary kidney.


Multisubunit DNA-Dependent RNA Polymerases from Vaccinia Virus and Other Nucleocytoplasmic Large-DNA Viruses: Impressions from the Age of Structure.
The past 17 years have been marked by a revolution in our understanding of cellular multisubunit DNA-dependent RNA polymerases (MSDDRPs) at the structural level. A parallel development over the past 15 years has been the emerging story of the giant viruses, which encode MSDDRPs. Here we link the two in an attempt to understand the specialization of multisubunit RNA polymerases in the domain of life encompassing the large nucleocytoplasmic DNA viruses (NCLDV), a superclade that includes the giant viruses and the biochemically well-characterized poxvirus vaccinia virus. The first half of this review surveys the recently determined structural biology of cellular RNA polymerases for a microbiology readership. The second half discusses a reannotation of MSDDRP subunits from NCLDV families and the apparent specialization of these enzymes by virus family and by subunit with regard to subunit or domain loss, subunit dissociability, endogenous control of polymerase arrest, and the elimination/customization of regulatory interactions that would confer higher-order cellular control. Some themes are apparent in linking subunit function to structure in the viral world: as with cellular RNA polymerases I and III and unlike cellular RNA polymerase II, the viral enzymes seem to opt for speed and processivity and seem to have eliminated domains associated with higher-order regulation. The adoption/loss of viral RNA polymerase proofreading functions may have played a part in matching intrinsic mutability to genome size.


[Efficacy comparison of robotic and laparoscopic radical surgery in the treatment of middle-low rectal cancer].
To compare the clinical efficacy of robotic and laparoscopic radical surgery in the treatment of middle-low rectal cancers. From January 2015 to March 2016, intra-operative and postoperative follow-up data of 30 patients with middle-low rectal cancers who underwent robotic radical resection(robot group) and 32 patients with middle-low rectal cancers who underwent laparoscopic radical resection (laparoscopy group)n in our department were retrospectively collected. The distance from cancer to anal margin was less than 10 cm in both two groups and advanced rectal cancers were confirmed by preoperative colonoscopy biopsy. Associated data were compared between two groups. There were 13 males and 17 females in robot group with age of 27 to 85 (mean 59.7) years, disease course of 3 to 12 (mean 6.2) months and clinical stage T2-3N0-1. There were 16 males and 16 females in laparoscopic group with age of 32 to 79 (mean 60.3) years, disease course of 2 to 10(mean 5.9) months and clinical stage T2-3N0-1. The baseline data of two groups were not significantly different (all P>0.05). All the patients in two groups completed operations successfully without conversion to open operation. Compared with laparoscopic group, the blood loss was less [(100.3±43.7) ml vs. (150.3±68.2) ml, t=3.413, P=0.001], the first flatus time [(49.3±12.4) h vs. (58.6±12.5) h, t=2.838, P=0.006] and urinary catheter removal time [(3.0±0.7) d vs. (4.8±0.9) d, t=5.491, P=0.000] were shorter, while the operation time [(217.3±57.8) min vs. (187.9±23.1) min, t=2.772, P=0.009] was longer in robot group. No cancer tissue was observed in resection margin of two groups. Number of harvested lymph node per case (15.2±7.4 vs. 13.9±4.9, t=-0.764, P=0.448), distance from anal margin to tumor distal edge [(7±3) cm vs. (6.5±3) cm, t=-1.952, P=0.056] and postoperative hospital stay [(13.6±1.3) d vs. (13.8±1.8) d, t=0.925, P=0.359] were not significantly different between two groups. No serious complications occurred in two groups during intra-operative and postoperative period. During following up of 3 to 12 (average 8.7) months, 1 case of anastomotic fistula occurred in each group and was cured by conservative treatment without significant difference [3.3%(1/30) vs. 3.1%(1/32), P=1.000]. No sexual dysfunction was found in either groups. Two cases in laparoscopic group presented relapse and metastasis, but no recurrence and metastasis was observed in robot group. There was no death in two groups. Robotic radical surgery in the treatment of middle-low rectal cancers is safe and effective with the advantages of less trauma, less bleeding, rapid recovery of intestinal function and urinary function.


A collaborative screening program for the discovery of inhibitors of HCV NS2/3 cis-cleaving protease activity.
This report describes the development of a cell-based assay for high-throughput screening and detection of small-molecule inhibitors for hepatitis C virus (HCV) NS2/3 protease. The HCV NS2/3 protease is essential for the normal infectious cycle of HCV. Generation of a cell-based assay for this cis-acting viral protease involved reporter constructs in which the NS2/3 protease sequence was inserted between the ,B-lactamase (BLA) reporter and a ubiquitin-based destabilization domain. In stable cell lines, NS2/3 cis cleavage of the NS2/3-BLA fusion protein resulted in differential stability of the cleaved versus uncleaved BLA reporter, providing a robust readout for protease activity. BLA reporter activity was shown to be a function of NS2/3-specific protease activity, by using genetic mutants of the NS2/3 sequence. In addition, the cell-based assay was validated and screened in a 384-well format on a fully automated robotic platform where small-molecule inhibitors of NS2/3 protease activity were identified.


Left ventricular myxoma producing cardiac failure.
Seventy-five percent of primary cardiac tumors are benign, and most are myxomas. Seventy-five percent of myxomas originate from the left atrium, and 2.5% arise from the left ventricle. Heart failure is a rare complication of myxoma. A 54-year-old male patient with chronic obstructive pulmonary disease was admitted to the pulmonology department with a diagnosis of pneumonia and congestive heart failure during hospitalization. An echocardiography evaluation revealed a mobile mass (3.3 cm X 1.2 cm) in the left ventricle. The measured ejection fraction was 22%. Transthoracic and transesophageal echocardiography and magnetic resonance imaging examinations confirmed the presence of a myxoma in the left ventricle. The myxoma was a hanging mass with a stalk on the interventricular septum near the anterior mitral valve annulus. We visualized the gelatinous fragile mass on the septum; we then extracted the myxoma via a transaortic approach with the patient on cardiopulmonary bypass. The patient was discharged 10 days after surgery. Myxoma is treated by early surgical resection because of the potential for serious complications. Left ventricular myxomas have been reported to lead to a silent heart failure. This case is important because of its location and the patient's resultant heart failure.


High-Affinity Sites Form an Interaction Network to Facilitate Spreading of the MSL Complex across the X Chromosome in Drosophila.
Dosage compensation mechanisms provide a paradigm to study the contribution of chromosomal conformation toward targeting and spreading of epigenetic regulators over a specific chromosome. By using Hi-C and 4C analyses, we show that high-affinity sites (HAS), landing platforms of the male-specific lethal (MSL) complex, are enriched around topologically associating domain (TAD) boundaries on the X chromosome and harbor more long-range contacts in a sex-independent manner. Ectopically expressed roX1 and roX2 RNAs target HAS on the X chromosome in trans and, via spatial proximity, induce spreading of the MSL complex in cis, leading to increased expression of neighboring autosomal genes. We show that the MSL complex regulates nucleosome positioning at HAS, therefore acting locally rather than influencing the overall chromosomal architecture. We propose that the sex-independent, three-dimensional conformation of the X chromosome poises it for exploitation by the MSL complex, thereby facilitating spreading in males.


Prediction of mucositis risk secondary to cancer therapy: a systematic review of current evidence and call to action.
Despite advances in personalizing the efficacy of cancer therapy, our ability to identify patients at risk of severe treatment side effects and provide individualized supportive care is limited. This is particularly the case for mucositis (oral and gastrointestinal), with no comprehensive risk evaluation strategies to identify high-risk patients. We, the Multinational Association for Supportive Care in Cancer/International Society for Oral Oncology (MASCC/ISOO) Mucositis Study Group, therefore aimed to systematically review current evidence on that factors that influence mucositis risk to provide a foundation upon which future risk prediction studies can be based. We identified 11,018 papers from PubMed and Web of Science, with 197 records extracted for full review and 113 meeting final eligibility criteria. Data were then synthesized into tables to highlight the level of evidence for each risk predictor. The strongest level of evidence supported dosimetric parameters as key predictors of mucositis risk. Genetic variants in drug-metabolizing pathways, immune signaling, and cell injury/repair mechanisms were also identified to impact mucositis risk. Factors relating to the individual were variably linked to mucositis outcomes, although female sex and smoking status showed some association with mucositis risk. Mucositis risk reflects the complex interplay between the host, tumor microenvironment, and treatment specifications, yet the large majority of studies rely on hypothesis-driven, single-candidate approaches. For significant advances in the provision of personalized supportive care, coordinated research efforts with robust multiplexed approaches are strongly advised.


Neural bases of moderation of cortisol stress responses by psychosocial resources.
Psychosocial resources have been tied to lower psychological and biological responses to stress. The present research replicated this relationship and extended it by examining how differences in dispositional reactivity of certain neural structures may underlie this relationship. Two hypotheses were examined: (a) psychosocial resources are tied to decreased sensitivity to threat and/or (b) psychosocial resources are associated with enhanced prefrontal inhibition of threat responses during threat regulation. Results indicated that participants with greater psychosocial resources exhibited significantly less cortisol reactivity following a stress task, as predicted. Analyses using functional magnetic resonance imaging revealed that psychosocial resources were associated with greater right ventrolateral prefrontal cortex and less amygdala activity during a threat regulation task but were not associated with less amygdala activity during a threat sensitivity task. Mediational analyses suggest that the relation of psychosocial resources to low cortisol reactivity was mediated by lower amygdala activity during threat regulation. Results suggest that psychosocial resources are associated with lower cortisol responses to stress by means of enhanced inhibition of threat responses during threat regulation, rather than by decreased sensitivity to threat.


Evolution and acceptability of medical applications of RFID implants among early users of technology.
RFID as a wireless identification technology that may be combined with microchip implants have tremendous potential in today's market. Although these implants have their advantages and disadvantages, recent improvements how allowed for implants designed for humans. Focus was given to the use of RFID tags and its effects on technology and CRM through a case study on VeriChip, the only corporation to hold the rights and the patent to the implantable chip for humans, and an empirically based study on working professionals to measure perceptions by early adopters of such technology. Through hypotheses-testing procedures, it was found that although some resistance to accept microchip implants was found in several applications, especially among gender, it was totally expected that healthcare and medical record keeping activities would be universally treated in a positive light and the use of authorities (namely governmental agencies) would be equally treated in a negative light by both sexes. Future trends and recommendations are presented along with statistical results collected through personal interviews.


Scdrake: a reproducible and scalable pipeline for scRNA-seq data analysis.
While the workflow for primary analysis of single-cell RNA-seq (scRNA-seq) data is well established, the secondary analysis of the feature-barcode matrix is usually done by custom scripts. There is no fully automated pipeline in the R statistical environment, which would follow the current best programming practices and requirements for reproducibility. We have developed scdrake, a fully automated workflow for secondary analysis of scRNA-seq data, which is fully implemented in the R language and built within the drake framework. The pipeline includes quality control, cell and gene filtering, normalization, detection of highly variable genes, dimensionality reduction, clustering, cell type annotation, detection of marker genes, differential expression analysis and integration of multiple samples. The pipeline is reproducible and scalable, has an efficient execution, provides easy extendability and access to intermediate results and outputs rich HTML reports. Scdrake is distributed as a Docker image, which provides a straightforward setup and enhances reproducibility. The source code and documentation are available under the MIT license at https://github.com/bioinfocz/scdrake and https://bioinfocz.github.io/scdrake, respectively. Supplementary data are available at Bioinformatics Advances online.


Antihyperalgesic effect of joint mobilization requires Cav3.2 calcium channels.
The present study was undertaken to explore the relative contributions of Cav3.2 T-type channels to mediating the antihyperalgesic activity of joint manipulation (JM) therapy. We used the chronic constriction injury model (CCI) to induce peripheral neuropathy and chronic pain in male mice, followed by JM. We demonstrate that JM produces long-lasting mechanical anti-hyperalgesia that is abolished in Cav3.2 null mice. Moreover, we found that JM displays a similar analgesic profile as the fatty acid amide hydrolase inhibitor URB597, suggesting a possible converging mechanism of action involving endocannabinoids. Overall, our findings advance our understanding of the mechanisms through which JM produces analgesia.


Effectiveness of nursing intervention in the operating room to prevent pressure ulcer and wound infection in patients undergoing intertrochanteric fracture: A meta-analysis.
In this study, a meta-analysis was conducted to comprehensively assess the effectiveness of nursing intervention in the operating room to prevent pressure ulcers and wound infections in patients with intertrochanteric fractures. A computerised search of PubMed, Cochrane Library, Embase, China National Knowledge Infrastructure (CNKI), VIP Database of Chinese Technical Periodicals, and Wanfang databases was performed to identify randomised controlled studies (RCTs) on the effectiveness of nursing intervention in the operating room for patients undergoing intertrochanteric fractures from the time of construction of the respective databases to June 2023. Two researchers independently searched and screened the literature, extracted information and performed quality assessments of the included literature. The meta-analysis was performed using RevMan 5.4 software. Eighteen studies were finally included, including 1517 patients, with 757 in the intervention group and 760 in the control group. The results showed that nursing intervention in the operating room significantly reduced the incidence of postoperative pressure ulcers in patients with intertrochanteric femoral fractures compared to the control group (1.69% vs. 6.01%, odds ratio [OR]: 0.32, 95% confidence interval [CI]: 0.18-0.57, p < 0.001) and reduced the incidence of surgical site wound infection (1.00% vs. 6.15%, OR: 0.23, 95% CI: 0.11-0.50, p < 0.001). Current evidence suggests that nursing intervention in the operating room is superior to routine care in reducing the incidence of pressure ulcers and wound infections in patients with intertrochanteric fractures and that such interventions should be promoted for clinical use.


Structural enrichment for laboratory mice: exploring the effects of novelty and complexity.
Providing structural enrichment is a widespread refinement method for laboratory rodents and other animals in captivity. So far, animal welfare research has mostly focused on the effect of increased complexity either by accumulating or combining different enrichment items. However, increasing complexity is not the only possibility to refine housing conditions. Another refinement option is to increase novelty by regularly exchanging known enrichment items with new ones. In the present study, we used pair-housed non-breeding female C57BL/6J and DBA/2N mice to investigate the effect of novelty when applying structural enrichment. We used a double cage system, in which one cage served as home cage and the other as extra cage. While the home cage was furnished in the same way for all mice, in the extra cage we either provided only space with no additional enrichment items (space), a fixed set of enrichment items (complexity), or a changing set of enrichment items (novelty). Over 5 weeks, we assessed spontaneous behaviors, body weight, and extra cage usage as indicators of welfare and preference. Our main results showed that mice with access to structurally enriched extra cages (complexity and novelty) spent more time in their extra cages and complexity mice had lower latencies to enter their extra cages than mice with access to the extra cages without any structural enrichment (space). This indicates that the mice preferred the structurally enriched extra cages over the structurally non-enriched space cages. We found only one statistically significant difference between the novelty and complexity condition: during week 3, novelty mice spent more time in their extra cages than complexity mice. Although we did not detect any other significant differences between the novelty and complexity condition in the present study, more research is required to further explore the potential benefits of novelty beyond complexity.


Degradation of abamectin and doramectin on sheep grazed pasture.
Avermectins are widely used veterinary medicines. They bind strongly to faeces in their non-metabolized form and their half-life in faeces depends on field conditions. There are conflicting data regarding the behaviour of avermectins in the environment. Therefore, we investigated the degradation of abamectin and doramectin on sheep grazed pasture under field conditions in soil, soil-faeces and faeces samples from day 6 to day 70 (abamectin) or to day 50 (doramectin) after sheep treatment. Field conditions were recorded periodically during the experiment. Degradation of abamectin in sheep faeces and in soil-faeces was observed until day 60, with small amounts present in faeces until 70 days post treatment. Because the concentration of abamectin residues in soil was very low on day 6 after treatment, further significant degradation could not be measured. The concentration of doramectin in all analysed matrices decreased rapidly until day 50. It can be concluded that high concentrations of both avermectins were present during the first 20 days after treatment and that field conditions have an important role in degradation of avermectins on grazed pasture of treated animals. Clear identification of the consequences of avermectin exposure and the period of the greatest environmental risk will require further investigations.


Gene fusion analysis of membrane protein topology: a direct comparison of alkaline phosphatase and beta-lactamase fusions.
To compare two approaches to analyzing membrane protein topology, a number of alkaline phosphatase fusions to membrane proteins were converted to beta-lactamase fusions. While some alkaline phosphatase fusions near the N terminus of cytoplasmic loops of membrane proteins have anomalously high levels of activity, the equivalent beta-lactamase fusions do not. This disparity may reflect differences in the folding of beta-lactamase and alkaline phosphatase in the cytoplasm.


SVCT-2 in breast cancer acts as an indicator for L-ascorbate treatment.
L-ascorbate (L-ascorbic acid, vitamin C) clearly has an inhibitory effect on cancer cells. However, the mechanism underlying differential sensitivity of cancer cells from same tissue to L-ascorbate is yet to be clarified. Here, we demonstrate that L-ascorbate has a selective killing effect, which is influenced by sodium-dependent vitamin C transporter 2 (SVCT-2) in human breast cancer cells. Treatment of human breast cancer cells with L-ascorbate differentially induced cell death, dependent on the SVCT-2 protein level. Moreover, knockdown of endogenous SVCT-2 via RNA interference in breast cancer cells expressing high levels of the protein induced resistance to L-ascorbate treatment, whereas transfection with SVCT-2 expression plasmids led to enhanced L-ascorbate chemosensitivity. Surprisingly, tumor regression by L-ascorbate administration in mice bearing tumor cell xenograft also corresponded to the SVCT-2 protein level. Interestingly, SVCT-2 expression was absent or weak in normal tissues, but strongly detected in tumor samples obtained from breast cancer patients. In addition, enhanced chemosensitivity to L-ascorbate occurred as a result of caspase-independent autophagy, which was mediated by beclin-1 and LC3 II. In addition, treatment with N-acetyl-L-cysteine, a reactive oxygen species (ROS) scavenger, suppressed the induction of beclin-1 and LC3 II, implying that the differential SVCT-2 protein-dependent L-ascorbate uptake was attributable to intracellular ROS induced by L-ascorbate, subsequently leading to autophagy. These results suggest that functional SVCT-2 sensitizes breast cancer cells to autophagic damage by increasing the L-ascorbate concentration and intracellular ROS production and furthermore, SVCT-2 in breast cancer may act as an indicator for commencing L-ascorbate treatment.


Revealing the roles of Hamiltonian coupling in bound-state quantum systems.
A Hamiltonian coupling identification (HCI) technique is introduced to reveal the independent and cooperative roles of Hamiltonian matrix elements in determining the bound-state energies of quantum systems. The HCI technique operates by encoding each Hamiltonian matrix element with a unique modulation signal, producing a nonlinear signature in the energy eigenvalues that may be decoded to reveal the contributing coupling structure in the Hamiltonian. The HCI technique is capable of exploring the roles of Hamiltonian coupling structure within and beyond the convergence limits of standard perturbation theory expansions. The flexibility residing in the encoding and decoding processes may be exploited to tailor the analysis to meet the desired degree of sought-after information about the Hamiltonian coupling structure. HCI, based on a Fourier encoding and decoding scheme, is illustrated by extracting information on the role of coupling interactions in the potential matrix elements of several simple model systems.


The effects of long-term antithyroid drug treatment on serum reverse T3 in patients with Graves' disease.
The effects of long-term treatment with antithyroid drugs, carbimazole (CMI) or propylthiouracil (PTU), on serum reverse triiodothyronine (rT3) levels were studied in 23 patients with Graves' disease. Nineteen patients were given CMI and four PTU for a minimum of six months. After one month of treatment the serum levels of thyroxine (T4), triiodothyronine (T3) and rT3 had normalized in both groups. When L-thyroxine was added to the regimens after two months of therapy, both serum T4 and rT3 levels increased, whereas serum T3 level continued to fall. The serum levels of rT3 seemed to be dependent on and followed the T4 levels so closely that determinations of rT3 in the medical management of patients with Graves' disease will be of little clinical use.


Acceptability of lifelong treatment among HIV-positive pregnant and breastfeeding women (Option B+) in selected health facilities in Zimbabwe: a qualitative study.
Zimbabwe's Ministry of Health and Child Care (MOHCC) adopted 2013 World Health Organization (WHO) prevention of mother-to-child HIV transmission (PMTCT) guidelines recommending initiation of HIV-positive pregnant and breastfeeding women (PPBW) on lifelong antiretroviral treatment (ART) irrespective of clinical stage (Option B+). Option B+ was officially launched in Zimbabwe in November 2013; however the acceptability of life-long ART and its potential uptake among women was not known. A qualitative study was conducted at selected sites in Harare (urban) and Zvimba (rural) to explore Option B+ acceptability; barriers, and facilitators to ART adherence and service uptake. In-depth interviews (IDIs), focus group discussions (FGDs) and key informant interviews (KIIs) were conducted with PPBW, healthcare providers, and community members. All interviews were audio-recorded, transcribed, and translated; data were coded and analyzed in MaxQDA v10. Forty-three IDIs, 22 FGDs, and five KIIs were conducted. The majority of women accepted lifelong ART. There was however, a fear of commitment to taking lifelong medication because they were afraid of defaulting, especially after cessation of breastfeeding. There was confusion around dosage; and fear of side effects, not having enough food to take drugs, and the lack of opportunities to ask questions in counseling. Participants reported the need for strengthening community sensitization for Option B+. Facilitators included receiving a simplified pill regimen; ability to continue breastfeeding beyond 6 months like HIV-negative women; and partner, community and health worker support. Barriers included distance of health facility, non-disclosure of HIV status, poor male partner support and knowing someone who had negative experience on ART. This study found that Option B+ is generally accepted among PPBW as a means to strengthen their health and protect their babies. Consistent with previous literature, this study demonstrated the importance of male partner and community support in satisfactory adherence to ART and enhancing counseling techniques. Strengthening community sensitization and male knowledge is critical to encourage women to disclose their HIV status and ensure successful adherence to ART. Targeting and engaging partners of women will remain key determinants to women's acceptance and adherence on ART under Option B+.


Neuroarchitecture of the central complex in the brain of the honeybee: Neuronal cell types.
The central complex (CX) in the insect brain is a higher order integration center that controls a number of behaviors, most prominently goal directed locomotion. The CX comprises the protocerebral bridge (PB), the upper division of the central body (CBU), the lower division of the central body (CBL), and the paired noduli (NO). Although spatial orientation has been extensively studied in honeybees at the behavioral level, most electrophysiological and anatomical analyses have been carried out in other insect species, leaving the morphology and physiology of neurons that constitute the CX in the honeybee mostly enigmatic. The goal of this study was to morphologically identify neuronal cell types of the CX in the honeybee Apis mellifera. By performing iontophoretic dye injections into the CX, we traced 16 subtypes of neuron that connect a subdivision of the CX with other regions in the bee's central brain, and eight subtypes that mainly interconnect different subdivisions of the CX. They establish extensive connections between the CX and the lateral complex, the superior protocerebrum and the posterior protocerebrum. Characterized neuron classes and subtypes are morphologically similar to those described in other insects, suggesting considerable conservation in the neural network relevant for orientation.


Control of circumferential wall stress and luminal shear stress within intact vascular segments perfused ex vivo.
Proportional, integral, and derivative (PID) controllers have proven to be robust in controlling many applications, and remain the most widely used control system architecture. The purpose of this work was to use this architecture for designing and tuning two PID controllers. The first was used to control the physiologic arterial circumferential wall stress (CWS) and the second to control the physiologic arterial shear stress (SS) imposed on intact vascular segments that were implanted into an ex vivo vascular perfusion system (EVPS). In order to most accurately control the stresses imposed onto vascular segments perfused ex vivo, analytical models were derived to calculate the CWS and SS. The mid-vein-wall CWS was calculated using the classical Lame solution for thick-walled cylinders in combination with the intraluminal pressure and outer diameter measurements. Similarly, the SS was calculated using the Hagen-Poiseuille equation in combination with the flow rate and outer diameter measurements. Performance of each controller was assessed by calculating the root mean square of the error (RMSE) between the desired and measured process variables. The performance experiments were repeated ten times (N=10) and an average RMSE was reported for each controller. RMSE standard deviations were calculated to demonstrate the reproducibility of the results. Sterile methods were utilized for making blood gas and temperature measurements in order to maintain physiologic levels within the EVPS. Physiologic blood gases (pH, pO(2), and pCO(2)) and temperature within the EVPS were very stable and controlled manually. Blood gas and temperature levels were recorded hourly for several (N=9) 24 h perfusion experiments. RMSE values for CWS control (0.427+/-0.027 KPa) indicated that the system was able to generate a physiologic CWS wave form within 0.5% error of the peak desired CWS over each cardiac cycle. RMSE values for SS control (0.005+/-0.0007 dynescm(2)) indicated that the system was able to generate a physiologic SS wave form within 0.3% error of the peak desired SS over each cardiac cycle. Physiologic pH, pO(2), pCO(2), and temperature levels were precisely maintained within the EVPS. The built-in capabilities and overall performance of the EVPS described in this study provide us with a novel tool for measuring molecular responses of intact vascular segments exposed to precisely simulated arterial biomechanical conditions.


Isolation and characterization of a bacteriophage infective for a UDP-galactose-4-epimeraseless mutant of Escherichia coli.
A DNA bacteriophage, designated CP13, was isolated against Escherichia coli J5, a UDP-galactose-4-epimeraseless mutant of E. coli 0111:B4. Bacteriophage CP13 appears to be specific for rough bacterial strains. Adsorption studies with E. coli J5 grown with galactose show that the bacteriophage will not adsorb when complete lipopolysaccharide is present in the cell membrane. This indicates that lipopolysaccharide may be directly or indirectly involved with the receptor site for bacteriophage CP13. The bacteriophage DNA has a G + C content of 52%.


Treatment of patients with geriatric depression with repetitive transcranial magnetic stimulation.
Repetitive transcranial magnetic stimulation (rTMS) has become a useful tool to treat different neuropsychiatric conditions such as depression, dementia and extrapyramidal syndromes insufficiently responding to conventional treatment. In this SHAM-controlled exploratory study safety, symptom improvement as well as changes in inflammation markers and neurotransmitter precursor amino acids availability were studied after a prefrontal cortex (PFC) stimulation using rTMS as add-on treatment in 29 patients with geriatric depression. Out of these, ten patients received SHAM treatment. Treatment was well tolerated, no serious adverse effects were observed. A clear improvement in symptoms of depression with a significant decrease in the HAMD-7 (U = 3.306, p = 0.001) was found by rTMS treatment. In parallel, serum phenylalanine dropped significantly (U = 2.340, p < 0.02), and there was a decline of tryptophan and of Phe/Tyr concentrations, both the effects, however, failed to reach the levels of statistical significance. In the patients who underwent SHAM treatment, no significant changes of HAMD-7 or the concentrations of any biomarker in the study could be found. In addition to the significant effect of rTMS on depression scores, these results point to a possible influence of rTMS on the enzyme phenylalanine hydroxylase (PAH), which plays a crucial role in the biosynthesis of neurotransmitter precursors related to geriatric depression.


Simultaneous Multimodal PC Access for People With Disabilities by Integrating Head Tracking, Speech Recognition, and Tongue Motion.
Multimodal Tongue Drive System (mTDS) is a highly integrated wireless assistive technology (AT) in the form of a lightweight wearable headset that utilizes three remaining key control and communication abilities in people with severe physical disabilities, such as tetraplegia, to provide them with effective access to computers: 1) tongue motion for discrete/switch-based control (e.g., clicking), 2) head tracking for proportional control (e.g., mouse pointer movements), and 3) speech recognition for typing, all available simultaneously. The mTDS architecture is presented here with new sensor signal processing algorithm for head tracking. To evaluate the device performance, it was compared against keyboard-and-mouse (KnM) combination, the gold standard in computer input methods, by 15 able-bodied participants, who used both mTDS and KnM to generate and sent an email with randomly selected content, under a 5-minute time constraint. In four repetitions, in the last trial, it took participants only 1.8 times longer to complete the email task, on average, using the mTDS versus KnM at 82.4% typing accuracy. Mean task completion time and typing accuracy improved 24.6% and 18.8% from first to fourth trial using mTDS. Multimodal simultaneous discrete and proportional control input options of mTDS, plus rapid typing, is expected to provide more effective computer access to people with severe physical disabilities.


Comparison of the decomposition VOC profile during winter and summer in a moist, mid-latitude (Cfb) climate.
The investigation of volatile organic compounds (VOCs) associated with decomposition is an emerging field in forensic taphonomy due to their importance in locating human remains using biological detectors such as insects and canines. A consistent decomposition VOC profile has not yet been elucidated due to the intrinsic impact of the environment on the decomposition process in different climatic zones. The study of decomposition VOCs has typically occurred during the warmer months to enable chemical profiling of all decomposition stages. The present study investigated the decomposition VOC profile in air during both warmer and cooler months in a moist, mid-latitude (Cfb) climate as decomposition occurs year-round in this environment. Pig carcasses (Sus scrofa domesticus L.) were placed on a soil surface to decompose naturally and their VOC profile was monitored during the winter and summer months. Corresponding control sites were also monitored to determine the natural VOC profile of the surrounding soil and vegetation. VOC samples were collected onto sorbent tubes and analyzed using comprehensive two-dimensional gas chromatography--time-of-flight mass spectrometry (GC × GC-TOFMS). The summer months were characterized by higher temperatures and solar radiation, greater rainfall accumulation, and comparable humidity when compared to the winter months. The rate of decomposition was faster and the number and abundance of VOCs was proportionally higher in summer. However, a similar trend was observed in winter and summer demonstrating a rapid increase in VOC abundance during active decay with a second increase in abundance occurring later in the decomposition process. Sulfur-containing compounds, alcohols and ketones represented the most abundant classes of compounds in both seasons, although almost all 10 compound classes identified contributed to discriminating the stages of decomposition throughout both seasons. The advantages of GC × GC-TOFMS were demonstrated for detecting and identifying trace levels of VOCs, particularly ethers, which are rarely reported as decomposition VOCs.


[Experiences with a centralised national service for autologous serum eyedrops in England].
The majority of patients with dry eye syndromes respond to conventional treatment aimed at optimising the ocular surface environment. There are some, however, who do not respond adequately to conventional lubricants. The first description of the use of autologous serum as a nutrient tears substitute was published more than 20 years ago. In 1997, NHS Blood and Transplant (NHSBT) developed a reliable and reproducible method for the production of eyedrops derived from autologous serum according to GMP Guidelines. The current cost of a batch of eyedrops (i. e. the product from one donation episode) is approximately 1300 GBP - this covers costs of collection, processing, testing and distribution. One "batch" of eyedrops will last for approximately 5 months if a bottle a day is used. A 6 month shelf life is put on the product and patients keep them in their domestic freezer.


The utility of thromboelastography in inherited and acquired bleeding disorders.
Thromboelastography (TEG) was first described by Hartert in 1948, and was designed to monitor viscoelastic clot strength in whole blood in real time. The current TEG method and Rotational Thromboelastometry (ROTEM) were subsequently developed from the original principles. Both of the modern methods provide data by measuring changes in the viscoelastic strength of a small sample of clotting blood in response to a constant rotational force. The important advantage of these techniques is to visually observe and quantify blood coagulation including the propagation, stabilization and dissolution phases of clot formation under low shear conditions. Analysis of the results provides detailed kinetic data on fibrin generation, clot strength and fibrinolysis. These TEG/ROTEM analyses therefore enable evaluation of global clotting function and the monitoring of haemostatic treatment in various clinical situations, not only in patients with genetic bleeding disorders, such as haemophilia, but also in patients undergoing cardiac surgery, liver transplantation or suffering from traumatic injury. Some evidence suggests that haemostatic management using TEG/ROTEM leads to a reduction in total transfusions of whole blood or clotting factors. Wider clinical application of this technology seems likely.


The iron-zinc interrelationship in the chick as influenced by Eimeria acervulina infection.
Two 14-day growth trials were performed to assess the effects of Eimeria acervulina infection (duodenal coccidiosis) on the Fe-Zn interrelationship in growing chicks. In the first assay, two levels of Fe (0 and 2000 mg/kg) were added to diets that contained either 0 or 52 mg supplemental Zn (from ZnCO3) per kilogram to establish whether excess Fe would affect Zn status of healthy and coccidial-infected chicks. In the second trial, either 0 or 2000 mg Zn/kg was added to diets containing 0 or 500 mg Fe/kg to determine whether Zn could modify Fe utilization. Based on chick performance as well as plasma Zn concentration, excess dietary Fe did not antagonize Zn in either healthy or E. acervulina-infected chicks. Coccidial infection, however, increased liver Fe and decreased intestinal Fe and hemoglobin concentration. Excess dietary Zn reduced performance and Fe content of tissues in both healthy and infected chicks. Coccidial infection ameliorated the adverse effects of excess Zn on performance and tissue Zn concentration and consequently enhanced Fe status of birds fed 2000 mg Zn/kg. These data suggest that the Fe-Zn interaction is a one-directional phenomenon in the chick, i.e., excess Zn reduces Fe utilization but excess Fe does not antagonize Zn.


A case of advanced rectal cancer with rectovesical and ileal fistulae that developed hyperammonemic encephalopathy.
Hyperammonemic encephalopathy is rarely caused by a urinary diversion. We herein experienced a case of rectal carcinoma with rectovesical and ileal fistulae that developed hyperammonemic encephalopathy. A 72-year-old man suffered from a fever, diarrhea, pneumaturia, and fecaluria beginning in April 2013 and was referred to our hospital in May 2013. He developed a loss of consciousness and whole body cramping on the first hospital day. The laboratory data indicated an inflammatory reaction and hyperammonemia with a highly elevated serum ammonia (NH3) level of 703 μg/dl. The patient was diagnosed to have rectal carcinoma with rectovesical and ileal fistulae according to computed tomography (CT) and a water-soluble contrast enema. We administered a solution of branched chain amino acids (BCAA) and antibiotics. Furthermore, we repeatedly irrigated bladder through the urethral catheter. The patient's symptoms recovered, and the serum ammonia levels on the second and third hospital day were decreased to 210 and 135 μg/dl, respectively. However, the symptoms of infection and confusion were suspected to repeat; we elected to perform surgical treatment. An ileal disconnection with ileocecal bypass and sigmoidostomy were effective for preventing hyperammonemic encephalopathy.


The influence of emotional distress on the outcome of in-vitro fertilization (IVF) and/or intracytoplasmic sperm injection (ICSI) treatment among infertile Turkish women.
To determine whether the emotional distress of infertile Turkish women is related to social support and influences the outcome of their IVF and/or ICSI treatment. The Beck Depression Inventory, State- Trait Anxiety Inventory, and Social Support scales were administered to 104 primary infertile Turkish women before the date of their embryo transfer. Comparisons were made between the women who became pregnant and those who did not following the embryo transfer. Compared to the pregnant women, the non-pregnant women had a greater number of emotional symptoms despite similar levels of social support. Also, the increased severity of depressive symptoms and higher levels of anxiety were predictive of low pregnancy rates. The pregnancy rate of infertile Turkish women was associated with emotional distress and low levels of social support were associated with increased emotional distress. Further research is needed to determine the factors and mechanisms that contribute to emotional distress in the treatment of infertility.


Inactivation of Salmonella enterica and Listeria monocytogenes inoculated on hydroponic tomatoes using chlorine dioxide gas.
The main objective of this study was to determine survivability of a cocktail of three strains of Salmonella enterica (Montevideo, Javiana, and Baildon) and two strains of Listeria monocytogenes (LCDC 81-861 and F4244) on hydroponic tomatoes after treatment with chlorine dioxide (ClO(2)) gas. An initial concentration of 8-9 log cfu/mL of Salmonella and Listeria cocktails was inoculated individually, in separate experiments, on tomato skin to obtain a population of 7-8 log cfu/cm(2) after drying of the inoculums on the tomato skin. The aim was to achieve a 5 log reduction consistent with the recommendations of the National Advisory Committee on Microbiological Criteria for Foods. The tomato skins were treated with 0.1, 0.3, and 0.5 mg/L ClO(2) gas for 12 min at 22 degrees C and at the relative humidity of 90%. Untreated skin samples were processed under the same conditions. ClO(2)-gas-treated and untreated samples were recovered by an overlay method. The bottom layer contains tryptic soy agar, and the top layer consists of xylose-lysine-desoxycholate agar or modified Oxford antimicrobial supplement agar for Salmonella and Listeria, respectively. More than a 5 log reduction in Salmonella and Listeria was observed on the tomato skin surfaces after treatment with 0.5 mg/L ClO(2) gas for 12 min. Treatment with 0.5 mg/L ClO(2) gas for 12 min also delayed the growth of natural microflora on tomato surfaces and extended the shelf life of tomatoes by 7 days during storage at 22 degrees C, compared with the untreated control. These results revealed that ClO(2) gas is a promising antimicrobial technology for fresh tomato skin surfaces.


Neuropsychiatric manifestations in patients of primary hyperparathyroidism and outcome following surgery.
A wide variety of psychiatric symptoms ranging from mild personality changes to severe depression and psychosis have been described in patients of PHPT. However, the psychiatric profile in Indian patients remains a mystery. It remains to be seen if surgery can alleviate the psychiatric morbidity and improve the quality of life of patients. Although, the pathophysiology remains largely unknown, we attempted to see if psychiatric morbidity correlated with serum calcium values. a) To study the nature and severity of neuropsychiatric manifestations in patients of hyperparathyroidism before surgery and their outcome after surgery b) To study their correlation with levels of serum calcium. This prospective study documented the occurrence of psychiatric symptoms among 14 patients of primary hyperparathyroidism (group I). 13 patients of gall stone disease (group II) and 12 patients of thyromegaly, undergoing total thyroidectomy (Group III) constituted the control groups. The relationship between such symptoms and degree of hypercalcemia was also studied. Assessment of psychologic symptoms, using the CPRS scale (validated in Hindi) and the scale for Memory and Intelligence for use in Hindi speaking population was carried out preoperatively and at 1 wk, 6 wk, 3, and 6 months postoperatively. The hyperaparathyroid group had significantly higher levels of total serum calcium and PTH preoperatively, with biochemical normalization postoperatively. The preoperative CPRS rating of the 14 patients with primary hyperparathyroidism revealed pronounced psychiatric symptoms, with a mean total CPRS score of 20 +/- 8.7, compared with 10.5 +/- 6.9(II) and 12.7 +/- 5.6 (III) in the control groups. Statistically significant improvement was seen in the CPRS score, maximally at 6 weeks post operatively for the following symptoms: Sadness, lassitude, ache and pains, and fatigability. There was no memory and intelligence impairment in any of the groups pre or post operatively. No correlation was found between the serum calcium levels and the psychiatric morbidity. The psychologic symptom distress is multidimensional and symptoms significantly improved by 6 weeks post parathyroidectomy. There was no memory and intelligence impairment in any of the groups pre or post operatively. No correlation was found between serum calcium levels and psychiatric morbidity.


Global Acute Myocardial Infarction Perspectives: Beyond Door-to-Balloon Interventions.
The goal in ST-elevation myocardial infarction (STEMI) intervention is achieving a door-to-balloon time of less than 90 minutes. Challenges in North America and Europe include patient education and implementing legislative mandates for STEMI guidelines. Globally, hurdles for primary percutaneous coronary intervention include limitations of access and financial constraints to providing STEMI care to vast populations. Adherence to North American and European guidelines globally remains an unrealistic goal given the unique cultural, demographic, and fiscal dynamics in poorer countries. The authors propose a four-phased population-based strategy for global acute myocardial infarction development and a pharmacoinvasive approach to STEMI care based on socioeconomic characteristics.


Molecular basis of altered excitability in Shaker mutants of Drosophila melanogaster.
Mutations in the Shaker (Sh) locus of Drosophila melanogaster have differing effects on action potential duration and repolarization in neurons as well as on A-type K+ channels (IA) in muscle. The molecular basis of three exemplary Sh alleles (ShKS133, ShE62 and Sh5) has been identified. They are point mutations in the Sh transcription unit expressing aberrant voltage-gated A-type K+ channels. Replicas of each mutation have been introduced by in vitro mutagenesis into Sh cDNA. The expression of in vitro transcribed mutant Sh cRNA in Xenopus laevis oocytes reproduced the specific phenotypic traits of each Sh allele. The lack of IA in ShKS133 is due to a missense mutation within a sequence motif occurring in all hitherto characterized voltage-gated K+ channel forming proteins. The reduction of IA in ShE62 is due to a mutation in an AG acceptor site. The intervening sequence between exons 19 and 20 is not spliced in ShE62 RNA. As a consequence, ShE62 flies do not contain the full complement of Sh K+ forming proteins. Finally, the Sh5 mutation leads to an altered voltage dependence of K+ channel activation and inactivation as well as to an accelerated rate of recovery from inactivation. This is due to a missense mutation altering the amino acid sequence of the proposed transmembrane segment S5 of the Sh K+ channels. Segment S5 is located adjacently to the presumed voltage sensor of voltage-gated ion channels. The results explain the altered properties of excitable cells in Sh mutants and provide a general model for the possible role of A-type K+ channels in modulating action potential profiles.


Aberrant Left Colic Artery and Its Surgical Implications.
Arterial anomalies of the viscera are not unusual. Of the arterial anomalies, the celiac and the superior mesenteric anomalies are well studied and reviewed in the literature. These variations are due to changes occurring during the development of vessels. Also, the variations in the colonic blood supply have been detailed in the context of conduit surgery in esophageal replacement and oncological resections. Of these, the rarer anomaly is the aberrant left colic artery (ab LCA). Previously described in various anatomic descriptions; it has never been reported in a clinical situation. A middle-aged female presented with abdominal pain and lower gastrointestinal (GI) bleed. On further evaluation, she was diagnosed to have transverse colon malignancy. She underwent extended right hemicolectomy with complete mesocolic excision and D3 lymphadenectomy as classically described. During the dissection, she was found to have an LCA arising from the superior mesenteric artery (SMA) just below the inferior border of the pancreas two centimeters higher to the origin of the middle colic artery. This artery was carefully dissected and preserved. Injury of the ab LCA is possible given the unusual course of the artery. Implications of iatrogenic injury in colonic and pancreatic surgeries may result in additional morbidity which is discussed in detail.


The effect of repair of the lacertus fibrosus on distal biceps tendon repairs: a biomechanical, functional, and anatomic study.
To date, repair of the lacertus in distal biceps tendon ruptures, recommended by some, has not been evaluated. The goal of these biomechanical experiments was to evaluate the degree to which its repair increases the strength of a distal biceps tendon repair. An intact or repaired lacertus fibrosus will increase the strength of a distal biceps tendon repair. Controlled laboratory study. Four matched pairs of fresh-frozen human cadaveric upper extremities were prepared by isolating the lacertus fibrosus and the distal biceps tendon. The extremity was placed in a custom-built rig with the distal biceps brachii clamped and affixed to a stepper motor assembly. The distal biceps tendon was sharply removed directly from the radial tuberosity and repaired through a bony tunnel in all specimens. One side of each pair was randomized to also receive repair of the lacertus. The specimens were pulled at a constant rate until failure. The mean failure strength, defined as maximal strength to 15 mm of displacement, was higher in specimens with a repaired lacertus (250.2 N vs 158.2 N; P =.012), as was mean maximum strength (256.8 N v. 164.5 N; P =.0058). Mean stiffness was not significantly different (16.36 N/mm vs 13.8 N/mm; P =.58). All specimens failed due to fracture at the bony bridge. Repair of the lacertus strengthened distal biceps tendon repair in a controlled laboratory setting. Repair of the lacertus fibrosus as an adjunct to distal biceps tendon repair strengthens the repair in the laboratory setting. Clinical testing is needed to verify that this increased strength improves clinical results. Surgeons should be cautioned to protect the underlying neurovascular structures during repair of the lacertus fibrosus and to avoid an overly tight repair.


Combined Stabilizing of the Solid-Electrolyte Interphase with Suppression of Graphite Exfoliation via Additive-Solvent Optimization in Li-Ion Batteries.
Propylene carbonate (PC) is a promising solvent for extending the operating temperature range for lithium-ion batteries (LIBs) because of its high dielectric constant and wide temperature range stability. However, PC can cause graphite exfoliation through cointercalation, leading to electrolyte decomposition and subsequent irreversible capacity loss. This work reports the formulation of a ternary electrolyte with the introduction of an inorganic salt additive, potassium hexafluorophosphate (KPF6), to address the aforementioned concerns. We demonstrate the cumulative effect of solvent and additive on delivering multiple performance benefits and safety of the battery. The faster diffusion rate of K + solvation shell decreases the rate of PC decomposition, thereby reducing its cointercalation. Additionally, the optimum concentration of KPF6, i.e., 0.1 M constructs a robust and insoluble LiF-rich electrode/electrolyte interphase, further suppressing graphite exfoliation and Li dendrite formation. The stable cyclability is achieved by enhanced Li + transportation through the LiF-rich interphase, enabling an exfoliation-free and dendrite-free graphite anode in the ternary electrolyte.


Consumption of fatty foods and incident type 2 diabetes in populations from eight European countries.
Diets high in saturated and trans fat and low in unsaturated fat may increase type 2 diabetes (T2D) risk, but studies on foods high in fat per unit weight are sparse. We assessed whether the intake of vegetable oil, butter, margarine, nuts and seeds and cakes and cookies is related to incident T2D. A case-cohort study was conducted, nested within eight countries of the European Prospective Investigation into Cancer (EPIC), with 12,403 incident T2D cases and a subcohort of 16,835 people, identified from a cohort of 340,234 people. Diet was assessed at baseline (1991-1999) by country-specific questionnaires. Country-specific hazard ratios (HRs) across four categories of fatty foods (nonconsumers and tertiles among consumers) were combined with random-effects meta-analysis. After adjustment not including body mass index (BMI), nonconsumers of butter, nuts and seeds and cakes and cookies were at higher T2D risk compared with the middle tertile of consumption. Among consumers, cakes and cookies were inversely related to T2D (HRs across increasing tertiles 1.14, 1.00 and 0.92, respectively; P-trend <0.0001). All these associations attenuated upon adjustment for BMI, except the higher risk of nonconsumers of cakes and cookies (HR 1.57). Higher consumption of margarine became positively associated after BMI adjustment (HRs across increasing consumption tertiles: 0.93, 1.00 and 1.12; P-trend 0.03). Within consumers, vegetable oil, butter and nuts and seeds were unrelated to T2D. Fatty foods were generally not associated with T2D, apart from weak positive association for margarine. The higher risk among nonconsumers of cakes and cookies needs further explanation.


A unique alpha dosimetry technique using Gafchromic EBT3(®) film and feasibility study for an activity calibrator for alpha-emitting radiopharmaceuticals.
To develop an alpha dosimetry technique for activity calibration of alpha-emitting radiopharmaceuticals using the Gafchromic(®) EBT3 (Gaf-EBT3) radiochromic film (International Speciality product, Wayne, NJ). The Gaf-EBT3 has a tissue equivalent radiosensitive layer (approximately 28 μm) sandwiched between two 100-μm thick polyester sheaths, thereby making it insensitive to alpha particles. We have split a Gaf-EBT3 sheet using a surgical scalpel to remove one of the polyester protective layers and covered the radiosensitive layer with thin Mylar(®) foil (Goodfellow Cambridge Limited, Huntingdon, UK) (2.5 μm). Small pieces of modified film were exposed at contact with a 560-Bq thin (241)Am source for 5, 10, 24 and 94 h. The optical density of the films was evaluated using an optical densitometer. The alpha energy spectra of the (241)Am source were recorded using a Si(Li) surface barrier detector. Time-integrated specific alpha surface activity (kBq cm(-2) h) was represented as a function of optical density. By removing one of the 100 μm thick polyester protective layers, the authors have modified the Gaf-EBT3 film to a sensitive alpha dosemeter. The calibration function relevant to a (241)Am reference source was evaluated from the optical densities of the dosemeter foils. Furthermore, calibration functions for important alpha emitters such as (223)Ra, (225)Ac or (210)Bi were parameterized from the (241)Am reference data. The authors have developed and tested the principle of a clinical alpha dosemeter using Gaf-EBT3 radiochromic films originally developed for photon dosimetry. This novel, user-friendly technique could be implemented in quality assurance and calibration procedures of important alpha-emitting radiopharmaceuticals prior to their clinical applications.


Multidimensional self-esteem and alcohol use among Mexican American and White non-Latino adolescents: concurrent and prospective effects.
Self-esteem was evaluated among Mexican American and White non-Latino adolescents. Three dimensions of self-esteem-(a) self-confidence, (b) competence, and (c) social acceptance-were assessed for concurrent and longitudinal relationships to alcohol use. Various concurrent relationships were found between dimensions of self-esteem and alcohol use. Only 1 prospective effect was found, among Mexican American female adolescents, indicating that prior poor self-confidence predicts higher levels of alcohol use.


Post-remission therapy for acute myeloid leukemia.
Induction followed by post-remission therapy including intensive chemotherapy with high-dose cytarabine, autologous and allogeneic hematopoietic stem cell transplantation is recognized as the main road towards cure in acute myeloid leukemia. In recent years, also a renaissance of maintenance therapy after completion of intensive consolidation has been observed with the introduction of kinase inhibitors and demethylating agents in clinical trials. Greater insight into the genetic background of the disease fostered the extension of disease classification and pretreatment risk-categorization by gene mutations. In addition, the pre-treatment risk-defining parameters have been supplemented by markers evaluated at distinct time points during treatment and follow up. In this context, minimal residual disease assessment is increasingly used to dynamically fine tune treatment recommendations. Currently, the gold standard to counterbalance a higher risk of relapse by treatment strategies based on hematopoietic stem cell transplantation with grafts from matched related or unrelated donors is still valuable, whereas autologous hematopoietic stem cell transplantation showed promising results especially in patients categorized as low-risk. Nonetheless, more targeted approaches including kinase inhibitors and demethylating agents in combination with or sequentially before or after intensive chemotherapy are currently in clinical evaluation and may lead to more genotype- instead of purely risk-adapted treatment strategies.


Aloe-emodin inhibits Staphylococcus aureus biofilms and extracellular protein production at the initial adhesion stage of biofilm development.
Staphylococcus aureus (S. aureus) biofilms are clinically serious and play a critical role in the persistence of chronic infections due to their ability to resist antibiotics. The inhibition of biofilm formation is viewed as a new strategy for the prevention of S. aureus infections. Here, we demonstrated that minimum inhibitory concentrations (MICs) of aloe-emodin exhibited no bactericidal activity against S. aureus but affected S. aureus biofilm development in a dose-dependent manner. Further studies indicated that aloe-emodin specifically inhibits the initial adhesion and proliferation stages of S. aureus biofilm development. Scanning electron microscopy (SEM) indicated that the S. aureus ATCC29213 biofilm extracellular matrix is mainly composed of protein. Laser scanning confocal microscope assays revealed that aloe-emodin treatment primarily inhibited extracellular protein production. Moreover, the Congo red assay showed that aloe-emodin also reduced the accumulation of polysaccharide intercellular adhesin (PIA) on the cell surface. These findings will provide new insights into the mode of action of aloe-emodin in the treatment of infections by S. aureus biofilms.


Folate and neural tube defects.
The multifactorial aetiology of neural tube defects has stimulated many theories related to dietary factors in pregnancy. The results of the Medical Research Council Study confirm that folate has a protective effect if taken in the 3 months prior to conception and for the first trimester. The dosage recommended is 5mg daily for women at risk for recurrence of spina bifida or anencephaly and 0.5mg daily for those at low risk. Dietary modification to include foods with high folate such as leafy green vegetables and wholemeal grain is not considered sufficient. Fortification of staple food items such as bread and cereals with folate is being considered in some countries. A comprehensive health education programme is essential, directed to women in the reproductive age group and to doctors involved in primary care, family planning and obstetric management. The incidence of neural tube defects could be reduced by 70% with the introduction of folate supplementation in all pregnancies.


N-acetyl-beta-glucosaminidase activity in serum of patients with epidermolysis bullosa.
A spectrophotometric study for serum N-acetyl-beta-glucosaminidase activity in patients with different types of epidermolysis bullosa and other bullous diseases was carried out. The activity in recessive type of epidermolysis bullosa dystrophica was higher than in dominant type of epidermolysis bullosa dystrophica and other bullous diseases. High levels of this enzymatic activity may be related to the metabolism of glycosaminoglycans, especially hyaluronic acid in recessive type of epidermolysis bullosa dystrophica.


[Nursing cooperation in surgical collection of testis tissues from prepubertal male patients for cryopreservation: A study of 4 cases].
To explore nursing cooperation in surgical collection of the testis tissue from prepubertal male patients for cryopreservation. We retrospectively analyzed the methods and effects of perioperative nursing in surgical collection of the testis tissue from 4 prepubertal male patients for cryopreservation in our Center of Reproductive Medicine. Before, during and after operation, we took strict measures in making sterilized ice containers, intraoperative nursing cooperation, protection of the isolated testis tissues and transferring of the samples. Testis tissues were successfully collected from all the 4 prepubertal males, 31, 31, 20 and 34 samples from each case respectively, well protected and subjected to slow cryopreservation after standard processing in the embryo laboratory. In surgical collection of the testis tissue for cryopreservation, preparation of sterilized ice containers, intraoperative nursing cooperation and protection and transferring of the samples are essential for standard processing and cryopreservation of the testis tissue in the embryo laboratory.


Induced production of 1-methoxy-indol-3-ylmethyl glucosinolate by jasmonic acid and methyl jasmonate in sprouts and leaves of pak choi (Brassica rapa ssp. chinensis).
Pak choi plants (Brassica rapa ssp. chinensis) were treated with different signaling molecules methyl jasmonate, jasmonic acid, linolenic acid, and methyl salicylate and were analyzed for specific changes in their glucosinolate profile. Glucosinolate levels were quantified using HPLC-DAD-UV, with focus on induction of indole glucosinolates and special emphasis on 1-methoxy-indol-3-ylmethyl glucosinolate. Furthermore, the effects of the different signaling molecules on indole glucosinolate accumulation were analyzed on the level of gene expression using semi-quantitative realtime RT-PCR of selected genes. The treatments with signaling molecules were performed on sprouts and mature leaves to determine ontogenetic differences in glucosinolate accumulation and related gene expression. The highest increase of indole glucosinolate levels, with considerable enhancement of the 1-methoxy-indol-3-ylmethyl glucosinolate content, was achieved with treatments of sprouts and mature leaves with methyl jasmonate and jasmonic acid. This increase was accompanied by increased expression of genes putatively involved in the indole glucosinolate biosynthetic pathway. The high levels of indole glucosinolates enabled the plant to preferentially produce the respective breakdown products after tissue damage. Thus, pak choi plants treated with methyl jasmonate or jasmonic acid, are a valuable tool to analyze the specific protection functions of 1-methoxy-indole-3-carbinole in the plants defense strategy in the future.


Evidence for importance of the Staphylococcus hyicus lipase pro-peptide in lipase secretion, stability and activity.
To investigate the function of the pro-peptide (PP) region of the Staphylococcus hyicus exolipase, restriction sites were created in the lipase gene to facilitate the construction of deletions in this region. Lipase gene expression was carried out in Staphylococcus carnosus. In the presence of the entire PP region, the 86-kDa pro-lipase was efficiently exported, had high lipolytic activity, and hardly any degradation products were seen in Western blot analysis. In addition to the 86-kDa pro-lipase, the membrane fraction contained a 106-kDa immunoreactive form. If the PP was completely or partially deleted, signal peptide processing, lipase secretion, lipase activity and/or lipase stability were impaired. The results obtained with lipase PP deletion mutants indicate that the PP region may have two functional domains. The N-terminal region of the lipase PP appears to be more important for lipase activity and the C-terminal portion for lipase secretion and proteolytic stability. In the presence of only the C-terminal part of the PP lipase, secretion was hardly affected. However, the activity of the extracellular lipase was markedly reduced. If only a small portion of the C-terminal part of the PP was present, lipase secretion was again markedly reduced and no lipase activity was detectable. In the presence of the N-terminal half of the PP region, lipase secretion was affected to a lesser extent. However, the resulting 60-kDa form, which showed comparably good specific lipase activity, suffered severe proteolytic degradation.


Frequency modulation of laser ultrasound transducer using carbon nanotube-coated polyethylene microsphere.
An ultrasound transducer was fabricated by dropping a multi-walled carbon nanotube solution containing a mixture of carbon nanotubes and ethoxyethanol directly on the surface of polyethylene microspheres. The frequency modulation depended on the diameter of the polyethylene microspheres. To investigate this relationship, three types of polyethylene microspheres with different diameters were used in simulations and experiments. These specimens were attached to polydimethylsiloxane and glass plates. A comparison revealed that the 50 μm diameter polyethylene spheres coated with carbon nanotubes had the highest ultrasound frequency. This work showed that smaller polyethylene microspheres generate higher ultrasound frequencies.


Eating disorders treatment patterns by age.
This longitudinal, retrospective study examines patterns in eating disorder outpatient mental health treatment by age. Participants (n = 5,445) included patients treated for an eating disorder, with claims for treatment from Cigna, a leading health care insurance provider in the United States. Treatments for individuals 55 and older were less expensive and shorter than for any other age group. Treatments for individuals 44-55 were less expensive than for 15-24. Individual therapy is the most common treatment modality, but younger individuals are likely to receive family therapy. Younger individuals have lower dropout and higher return to care rates.


Musculoskeletal magnetic resonance imaging.
In the short time that MRI has been available, it has become apparent that one of the more important nonneurologic applications is in imaging the musculoskeletal system. MRI is effective at providing high-contrast images with acceptable spatial resolution for a variety of bone marrow disorders, soft tissue masses, osseous tumors, and muscle diseases. The multiplanar aspect of the method is a great advantage and promises to be a major reason why MRI will be selected instead of CT for many examinations. Currently, it appears that MRI is a leading method of detecting ischemic necrosis of the femoral head and determining the extent of soft tissue masses and bone tumors. Surface coil technology promises better resolution of small parts such as the wrist and temporomandibular joint. Phosphorous spectroscopy should make important contributions to our basic understanding of normal and altered muscle energy metabolism as well as providing a safe method of following the course and therapy of muscle diseases. It is anticipated that MRI will have an important position among the variety of imaging tests for musculoskeletal diseases.


Carboxyl-Photo-Reactive MS-Cleavable Cross-Linkers: Unveiling a Hidden Aspect of Diazirine-Based Reagents.
A major challenge in cross-linking/mass spectrometry (MS) is targeting carboxyl functions in proteins under physiological conditions that do not disturb the protein's conformation. Cross-linking of glutamic acid and aspartic acid residues in proteins will greatly expand the scope of structural mass spectrometry. We discovered that carboxyl-reactive cross-linkers have already been employed for many years in cross-linking/MS studies, yet in a completely different context. Diazirine-based cross-linkers, such as photomethionine and succinimidyldiazirine cross-linkers, are currently considered to react nonspecifically upon UV-A photoactivation with all 20 proteinogenic amino acids through a reactive carbene that inserts mainly into C-H bonds. We discovered that the cross-linking capability of diazirines based on X-H (X = C, N, O) insertion is in fact only the tip of the iceberg. Diazirines isomerize to linear diazo compounds that can react with carboxylic acids to yield esters. On top of that, the resulting cross-linked products are MS-cleavable allowing an automated analysis of cross-links via customized software tools. Therefore, diazirines open an entirely new route for photo-cross-linking of carboxylic acids. Previous cross-linking studies using diazirines have to be revisited in the light of these findings.


[Prospective cohort study on the relationship between pathogenic bacteria in the nasal middle meatus and acute bacterial respiratory infection in children].
To study the relationship between pathogenic bacteria in the nasal middle meatus and acute bacterial respiratory infection in children. Three hundred and twenty eight children with respiratory infection (mean age 8 years) were included into the prospective cohort study. The mucosal fluid specimens from the nasal middle meatus were collected under an endoscope for bacterial culture. The patients with bacterial culture positive were defined as the Exposed group and those with bacterial culture negative as the Non-exposed group. The grouping of the patients was blinded to the patients, patients' parents and physicians. Both groups received anti-virus and symptomatic treatments, without antibiotic administration. Five days later, the patients were evaluated as to whether they had bacterial infection based on the leucocyte count and CRP results. Of the 328 patients, 168 had a positive nasal bacterial culture. The incidence of bacterial respiratory infection in the Exposed group [51.2% (86/168)] was significantly higher than in the Non-exposed group [13.1% (21/160)] (P < 0.01). The relative risk of bacterial respiratory infection occurrence in patients with nasal bacterial culture positive was 3.9002. The children with respiratory infection who had potential pathogenic bacteria in the nasal middle meatus were more prone to develop bacterial respiratory infection.


Superconducting nanowire single-photon sensing of cerebral blood flow.
Significance: The ability of diffuse correlation spectroscopy (DCS) to measure cerebral blood flow (CBF) in humans is hindered by the low signal-to-noise ratio (SNR) of the method. This limits the high acquisition rates needed to resolve dynamic flow changes and to optimally filter out large pulsatile oscillations and prevents the use of large source-detector separations ( ≥ 3 cm ), which are needed to achieve adequate brain sensitivity in most adult subjects. Aim: To substantially improve SNR, we have built a DCS device that operates at 1064 nm and uses superconducting nanowire single-photon detectors (SNSPD). Approach: We compared the performances of the SNSPD-DCS in humans with respect to a typical DCS system operating at 850 nm and using silicon single-photon avalanche diode detectors. Results: At a 25-mm separation, we detected 13 ± 6 times more photons and achieved an SNR gain of 16 ± 8 on the forehead of 11 subjects using the SNSPD-DCS as compared to typical DCS. At this separation, the SNSPD-DCS is able to detect a clean pulsatile flow signal at 20 Hz in all subjects. With the SNSPD-DCS, we also performed measurements at 35 mm, showing a lower scalp sensitivity of 31 ± 6 % with respect to the 48 ± 8 % scalp sensitivity at 25 mm for both the 850 and 1064 nm systems. Furthermore, we demonstrated blood flow responses to breath holding and hyperventilation tasks. Conclusions: While current commercial SNSPDs are expensive, bulky, and loud, they may allow for more robust measures of non-invasive cerebral perfusion in an intensive care setting.


[Blood bactericidal activity in calves under various lighting regimes].
Reported in this paper are the effects of varying lighting regimes on serum-bactericide capacity of calves, aged between 3 and 15 weeks. The results, first of all, have shown that the serum-bactericide system is affected by visible light. The reactivity of the complex defence system is reduced by extremely short days, as compared to extremely long days, with the animals being exposed to something between 80 and 100 lx, round the clock. Extremely long days were found to have positive effects on adaptation to changing environmental conditions, but negative effects of other abiotic factors of the environment could not be offset by visible light. Substitution of artificial light for natural light did not bring about any disadvantageous effects upon immunological reactivity of calves, aged between 3 and 15 weeks, under the authors' experimental conditions. Therefore, production in windowless structures is possible without any risk, provided that the fattening animals are kept in a properly controlled artificial light regime.


Bilateral rotatory subluxation of the scaphoid.
We describe the case of a 17-year-old girl, who presented to our Accident and Emergency (A&E) department following minor trauma to her forearm. Initial x-rays were misread as normal. Radiographs demonstrated classical features of rotatory subluxation of the scaphoid, which was found to be bilateral.


Supervised clustering of immunohistochemical markers to distinguish atypical and non-atypical endometrial hyperplasia.
The risk of endometrial hyperplasia (EH) progressing into endometrioid endometrial cancer ranges from 1% for simple EH without atypia (EHWA) to 46.2% for atypical EH (AEH). Differentiation between both entities is crucial to determine optimal management. As preoperative diagnosis of AEH can be difficult, we aimed to establish clusters of immunohistochemical markers to distinguish EHWA from AEH. We studied 13 immunohistochemical markers (steroid receptors, pro/anti-apoptotic proteins, metalloproteinases (MMP), tissue inhibitor of metalloproteinase (TIMP), CD44 isoforms) known for their role in endometrial pathology. Using supervised clustering, we determined clusters of co-expressed proteins which contributed the most in differentiating EHWA from AEH. From 39 tissue samples (17 EHWA and 22 AEH), we found three clusters of co-expressed proteins: Cluster 1 included two proteins (over-expression of estrogen receptor (ER) and under-expression of progesterone receptor (PR) B in AEH compared to EHWA); Cluster 2: an ER, PR A, MMP-2 and TIMP-1 over-expression and a PR B and TIMP-2 under-expression; Cluster 3: over-expression of ER and MMP-7 and under-expression of PR B and TIMP-2. AEH can be accurately distinguished from EHWA using a supervised clustering of immunohistochemical markers. This promising approach could be useful to improve the preoperative diagnosis of EH.


Neurodegeneration with brain iron accumulation--late onset slowly progressive variant.
Neurodegeneration with Brain Iron Accumulation (NBIA) is a rare type of neuroaxonal dystrophy that can be familial or sporadic, characterized by progressive extrapyramidal degeneration. We report a case of 23 year old male who presented with cervical dystonia, dysarthria and MRI brain suggestive of characteristic "eye-of-the-tiger" appearance in the globus pallidus.


The 'Seamless Web': the development of the electronic patient record in Aarhus region, Denmark.
The article surveys the organization of the current project to develop an electronic patient record in the Aarhus Region, Denmark. The article is based on various policy documents and reports as well as a number of semi-structured interviews with project managers from the EPR organization in Aarhus County and with participants in the development process at local hospitals. This material is used to present and discuss the framing of the project in a 'discourse coalition'. The stabilization of a specific discourse coalition has been an important factor in ensuring the success of the development project up to the present moment. This coalition became relatively stable by integrating a diverse set of actors in a story-line about the relationships between co-operation, management and technology in the medial sector, and has influenced the modular organization of the project. The successful maintenance of the discourse coalition allows the project to appear 'seamless' from the outside. Conversely, the project is likely to be continually reviewed as successful only to the extent that it is able to flexibly keep the fluctuating set of relevant actors in alignment. If the practical work of keeping a coalition in place remains invisible it becomes easy to imagine an ideal way of planning large socio-technical projects, like developing an ECR. But practical success is more likely to be achieved if one takes seriously the thorough intertwining of discursive, organizational and technical aspects of development projects.


Cancer support groups: a critical review of empirical studies.
Support groups for adults affected by cancer are widely offered by local community and national agencies in North America. This type of psychosocial intervention is defined in terms of its structure and functions, and its theoretical underpinnings and models of practice are described. Forty-four empirical studies of professionally led cancer support groups are summarized and critically reviewed. These studies include 32 outcome evaluations of randomized controlled trials, two process evaluations, and 10 consumer satisfaction studies. The findings reveal high levels of consumer satisfaction, and the outcome evaluations substantiate the morale and other quality of life benefits short of prolonging life. Discussion centers on priorities for future research and practice.


Spontaneous vegetation succession at different central European mining sites: a comparison across seres.
We performed detrended correspondence analysis (DCA) ordination to compare seven successional seres running in stone quarries, coal mining spoil heaps, sand and gravel pits, and extracted peatlands in the Czech Republic in central Europe. In total, we obtained 1,187 vegetation samples containing 705 species. These represent various successional stages aged from 1 to 100 years. The successional seres studied were more similar in their species composition in the initial stages, in which synathropic species prevailed, than in later successional stages. This vegetation differentiation was determined especially by local moisture conditions. In most cases, succession led to a woodland, which usually established after approximately 20 years. In very dry or wet places, by contrast, where woody species were limited, often highly valuable, open vegetation developed. Except in the peatlands, the total number of species and the number of target species increased during succession. Participation of invasive aliens was mostly unimportant. Spontaneous vegetation succession generally appears to be an ecologically suitable and cheap way of ecosystem restoration of heavily disturbed sites. It should, therefore, be preferred over technical reclamation.


Progress in hematopoietic stem cell transplantation in multiple myeloma.
An attempt is made to value the place of autologous and allogeneic hematopoietic stem cell transplantation in the treatment of multiple myeloma. Recent progress with each treatment modality has significantly changed the outcome for myeloma patients. The gold standard for conditioning treatment before autologous transplantation is melphalan 200 mg/m, and the use of peripheral blood stem cells is superior to that of bone marrow. Tandem autologous transplantation is superior to single autologous transplantation, at least for patients who do not respond with complete remission to the first transplant. Allogeneic transplantation using standard high-dose myeloablative conditioning reduces the relapse rate in comparison with autologous transplantation; however, treatment-related mortality is significantly higher. Progress in allogeneic transplantation has been significant, and transplant-related mortality has been reduced. The recent use of nonmyeloablative reduced-intensity conditioning has significantly decreased transplant-related mortality; however, the relapse rate is higher than with standard conditioning, and therefore no significant improvement in overall survival has as yet been seen. Relapse following allogeneic transplantation can be counteracted by donor lymphocyte infusions, but the survival results are so far inconclusive. Autologous transplantation is still the first choice for most myeloma patients, but it does not seem to be curative. Therefore, allogeneic transplantation should be continued in clinical trials exploring new conditioning methods, the graft-versus-myeloma effect of new cell types, and its combination with new targeted drugs such as bortezomib and lenalidomide.


Prevalence and Risk Factors of Mortality among Adult HIV Patients Initiating ART in Rural Setting of HIV Care and Treatment Services in North Western Tanzania: A Retrospective Cohort Study.
HIV still causes high mortality despite use of ART. This study was designed to determine the prevalence and risk factors of mortality among HIV patients receiving ART in northwestern rural Tanzania. A retrospective study of HIV patients on ART was done at Sengerema in Mwanza, Tanzania. The data on demography, date of HIV diagnosis, WHO stage, opportunistic infections, CD4, hemoglobin, ART regimen, and time and outcome on treatment as dead or alive were collected and analyzed using STATA version 11. In total, 740 patients were studied. The median age was 35 (27-42) years with female predominance of 465 (62.8%). Of the participants, 261 (35.3%) had WHO stages 3 and 4 diseases. Most participants, 258 (34.9%), had baseline CD4 counts <200 cells/μl. Deaths occurred in 86 (11.6%) patients which were independently associated with male gender (16.0% versus 9.0%, p = 0.015), being divorced (OR = 2.7, p < 0.001), WHO stages 3 and 4 (OR = 2.3, p = 0.05), CD4 <200 cells/μl (OR = 3.4, p < 0.001), and severe anemia (OR = 6.6, p < 0.001). The mortality is high among HIV patients receiving ART in northwestern rural Tanzania. Universal testing could increase early diagnosis and treatment. A close follow-up of at-risk patients within the first year of ART could reduce the mortality of this subgroup of patients.


Effects of glucagon-like peptide-1, yohimbine, and nitrergic modulation on sympathetic and parasympathetic activity in humans.
Glucagon-like peptide-1 (GLP-1), an incretin, which is used to treat diabetes mellitus in humans, inhibited vagal activity and activated nitrergic pathways. In rats, GLP-1 also increased sympathetic activity, heart rate, and blood pressure (BP). However, the effects of GLP-1 on sympathetic activity in humans are unknown. Our aims were to assess the effects of a GLP-1 agonist with or without alpha(2)-adrenergic or -nitrergic blockade on autonomic nervous functions in humans. In this double-blind study, 48 healthy volunteers were randomized to GLP-1-(7-36) amide, the nitric oxide synthase (NOS) inhibitor N(G)-monomethyl-l-arginine acetate (l-NMMA), the alpha(2)-adrenergic antagonist yohimbine, or placebo (i.e., saline), alone or in combination. Hemodynamic parameters, plasma catecholamines, and cardiac sympathetic and parasympathetic modulation were measured by spectral analysis of heart rate. Thereafter, the effects of GLP-1-(7-36) amide on muscle sympathetic nerve activity (MSNA) were assessed by microneurography in seven subjects. GLP-1 increased (P = 0.02) MSNA but did not affect cardiac sympathetic or parasympathetic indices, as assessed by spectral analysis. Yohimbine increased plasma catecholamines and the low-frequency (LF) component of heart rate power spectrum, suggesting increased cardiac sympathetic activity. l-NMMA increased the BP and reduced the heart rate but did not affect the balance between sympathetic and parasympathetic activity. GLP-1 increases skeletal muscle sympathetic nerve activity but does not appear to affect cardiac sympathetic or parasympathetic activity in humans.


Flow cytometric evaluation of anti-herpes drugs.
A rapid means of screening drugs for toxicity and anti-herpes simplex virus activity was developed based on the flow cytometric detection of HSV induced changes in cellular DNA content. Subconfluent monolayers of human diploid fibroblasts (HEL 299) were assayed for DNA content with propidium iodide 24 h after infection with HSV-1 (multiplicity of infection 1-10) and treatment with the drug to be tested. Infection was detected by a broadening of the normal diploid and tetraploid peaks and presence of greater than 4-n DNA staining. Inhibition of viral DNA synthesis and maintenance of the normal growth pattern of control cells was indication of antiviral activity. Toxicity of the compound was indicated by the loss of S phase and tetraploid cell populations. Using this assay, we evaluated the activities of one experimental and two established antiviral agents.


B(C6F5)3-Catalyzed α,β-Difunctionalization and C-N Bond Cleavage of Saturated Amines with Benzo[c]isoxazoles: Access to Quinoline Derivatives.
Herein, we disclose a strategy to realize α,β-difunctionalization and C-N bond cleavage of saturated amines with benzo[c]isoxazoles via a B(C6F5)3-catalyzed consecutive hydrogen-borrowing and [4 + 2] cycloaddition followed by a C-N bond cleavage process. In general, the reactions proceed efficiently in the absence of any oxidant and metal catalyst to afford a broad range of quinoline derivatives starting from easily accessible substrates in an atom-economical manner.


The oral health assessment tool--validity and reliability.
The Oral Health Assessment Tool (OHAT) was a component of the Best Practice Oral Health Model for Australian Residential Care study. The OHAT provided institutional carers with a simple, eight category screening tool to assess residents' oral health, including those with dementia. This analysis presents OHAT reliability and validity results. A convenience sample of 21 residential care facilities (RCFs) in urban and rural Victoria, NSW and South Australia used the OHAT at baseline, three-months and six-months to assess intra- and inter-carer reliability and concurrent validity. Four hundred and fifty five residents completed all study phases. Intra-carer reliability for OHAT categories: percent agreement ranged from 74.4 per cent for oral cleanliness, to 93.9 per cent for dental pain; Kappa statistics were in moderate range (0.51-0.60) for lips, saliva, oral cleanliness, and for all other categories in range of 0.61-0.80 (substantial agreement) (p < 0.05). Inter-carer reliability for OHAT categories: percent agreement ranged from 72.6 per cent for oral cleanliness to 92.6 per cent for dental pain; Kappa statistics were in moderate range (0.48-0.60) for lips, tongue, gums, saliva, oral cleanliness, and for all other categories in range of 0.61-0.80 (substantial agreement) (p < 0.05). Intraclass correlation coefficients for OHAT total scores were 0.78 for intra-carer and 0.74 for inter-carer reliability. Validity analyses of the OHAT categories and examination findings showed complete agreement for the lips category, with the natural teeth, dentures, and tongue categories having high significant correlations and percent agreements. The gums category had significant moderate correlation and percent agreement. Non-significant and low correlations and percent agreements were evident for the saliva, oral cleanliness and dental pain categories. The Oral Health Assessment Tool was evaluated as being a reliable and valid screening assessment tool for use in residential care facilities, including those with cognitively impaired residents.


Sexual partners, sexually transmitted infections, and prostate cancer risk.
The etiology of prostate cancer (PCa) is poorly understood. Sexual activity and sexually transmitted infections (STIs) are among factors under scrutiny, with controversial findings to date. We examined the association between the number and gender of sexual partners, STIs and PCa risk in the context of PROtEuS, a population-based case-control study set amongst the mainly French-speaking population in Montreal, Canada. The study included 1590 histologically-confirmed PCa cases diagnosed in a Montreal French hospital between 2005 and 2009, and 1618 population controls ascertained from the French electoral list, Montreal residents, frequency-matched to cases by age. In-person interviews elicited information on sociodemographic, lifestyle and environmental factors. Unconditional logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between sexually related factors and PCa risk, adjusting for age, ancestry, family history of PCa, and PCa screening history. Subjects with more than 20 sexual partners in their lifetime had a decreased risk of PCa (OR 0.78, 95% CI 0.61-1.00) as did subjects who specifically had more than 20 female sexual partners (OR 0.72, 95% CI 0.56-0.94). By contrast, having had several male sexual partners appeared to confer some excess in risk of PCa. No association emerged for history of STIs and PCa but STIs prevalence was low. Our findings are in support of a role for the number of sexual partners in PCa development. The gender of sexual partners should be taken into account in future studies investigating this association.


Comparative expression patterns and diagnostic efficacies of SR splicing factors and HNRNPA1 in gastric and colorectal cancer.
Serine/arginine-rich splicing factors (SRSFs) and HNRNPA1 have oncogenic properties. However, their proteomic expressions and practical priority in gastric cancer (GC) and colorectal cancer (CRC) are mostly unknown. To apply SFs in clinics, effective marker selection and characterization of properties in the target organ are essential. We concurrently analyzed SRSF1, 3, and 5-7, and HNRNPA1, together with the conventional tumor marker carcinoembryonic antigen (CEA), in stomach and colorectal tissue samples (n = 420) using semiquantitative immunoblot, subcellular fractionation, and quantitative real-time polymerase chain reaction methods. In the semiquantitative immunoblot analysis, HNRNPA1 and SRSF7 levels were significantly higher in GC than in gastric normal mucosa, and SRSF7 levels were higher in intestinal-type compared with diffuse-type of gastric adenocarcinoma. Of the SFs, only HNRNPA1 presented greater than 50 % upregulation (cancer/normal mucosa > 2-fold) incidences and CEA-comparable, acceptable (>70 %) detection accuracy (74 %) for GC. All SF protein levels were significantly higher in CRC than in colorectal normal mucosa, and HNRNPA1 levels were higher in low-stage CRC compared with high-stage CRC. Among the SFs, HNRNPA1 and SRSF3 presented the two highest upregulation incidences (88 % and 74 %, respectively) and detection accuracy (90 % and 84 %, respectively) for CRC. The detection accuracy of HNRNPA1 was comparable to that of CEA in low (≤ II)-stage CRC but was inferior to that of CEA in high (>II)-stage CRC. Extranuclear distributions of HNRNPA1 and SRSF6 (cytosol/microsome) differed from those of other SRSFs (membrane/organelle) in both cancers. In an analysis of the six SF mRNAs, all mRNAs presented unacceptable detection accuracies (≤70 %) in both cancers, and all mRNAs except SRSF6 were disproportionate to the corresponding protein levels in GC. Our results provide a comprehensive insight into the six SF expression profiles in GC and indicate that, among the SFs, HNRNPA1, but not HNRNPA1 mRNA, is the most effective, novel GC marker. Regardless of the good to excellent detection accuracy of SRSF3 and HNRNPA1 in CRC, the SFs have lower practical priority than CEA, especially for high-stage CRC detection.


Evaluation of treatment programs for persons with severe mental illness: moderator and mediator effects.
This study evaluated several statistical models for estimating treatment effects in a randomized, longitudinal experiment comparing assertive community treatment (ACT) versus brokered case management (BCM). In addition, mediator and moderator analyses were conducted. The ACT clients had improved outcomes in terms of housing and psychiatric symptoms than BCM clients. Case management housing assistance and financial assistance partially mediated housing outcomes. No reliable mediators were found for psychiatric symptoms, and no reliable moderators were found for either housing or psychiatric symptoms. The study also made several important methodological advances in the analysis of longitudinal data in randomized experiments.