Spatiotemporal activation of Rac1 for engulfment of apoptotic cells.
The engulfment of apoptotic cells requires phagocytes to coordinately activate Rho family GTPases that regulate actin dynamics. Here, we used a FRET biosensor to visualize the spatiotemporal activation of Rac1 during engulfment of apoptotic cells. We report that apoptotic cells were usually engulfed by the phagocytes' lamellipodia, where Rac1 was activated. Often, apoptotic cells were engulfed successively at the same lamellipodial site, suggesting the presence of portals for apoptotic cells. At this location, the activated Rac1 was recruited to form phagocytic cups that were comprised of actin patches. When the phagocytic cup was closed, Rac1 was down-regulated, and the actin patches were abruptly broken down. The constitutively active Rac1 remained at phagocytic cup for a longer period than the wild-type Rac1, and the closure of the phagocytic cup was significantly delayed in cells expressing a constitutive active form of Rac1, resulting in inefficient engulfment. These results indicate that activated Rac1 is necessary to assemble F-actin, but closing the phagocytic cup requires Rac1 to be deactivated.


Cefpirome sulphate for gynaecological infections and prophylaxis of non-laparotomy surgery in patients with benign disease.
We organized a study group to conduct a clinical trial in patients with various gynaecological infections, and we also assessed the efficacy of a single dose of cefpirome sulphate as prophylaxis after vaginal hysterectomy. Cefpirome sulphate (CROM) was administered to 100 patients with gynaecological infections and the clinical and antibacterial efficacy was evaluated in 88 patients. The improvement rate was 77.0% (67/87) and the bacterial eradication rate 67.8% (40/59). Nineteen of the 210 patients enrolled in the comparison of CROM with cefmetazole sodium (CMET) prophylaxis developed postoperative infections. The incidence of infection showed no significant difference between the CROM group (n=11, 10.6%) and the CMET group (n=8, 7.5%) (P=0.56). Although these results suggest that CROM may be effective for the treatment of gynaecological infections and has a good safety profile, it was not superior to CMET as prophylaxis in women undergoing non-laparotomy procedures at our hospital.


Infrared multiphoton dissociation and electron-induced dissociation as alternative MS/MS strategies for metabolite identification.
A major challenge encountered in mass spectrometric metabolite analysis is the identification and structural characterization of metabolites. Fourier transform ion cyclotron resonance mass spectrometry is a valuable technique for metabolite structural determination because it provides accurate masses and allows for multiple MS/MS fragmentation strategies, including infrared multiphoton dissociation (IRMPD) and electron-induced dissociation (EID). Collision activated dissociation (CAD) is currently the most commonly used MS/MS technique for metabolite structural characterization. In contrast, IRMPD and EID have had very limited, if any, application for metabolite characterization. Here, we explore IRMPD and EID of phosphate-containing metabolites and compare the resulting fragmentation patterns to those of CAD. Our results show that CAD, IRMPD, and EID provide complementary structural information for phosphate-containing metabolites. Overall, CAD provided the most extensive fragmentation for smaller (<600 Da) phosphate-containing metabolites; however, IRMPD generated more extensive fragmentation for larger (>600 Da) phosphate-containing metabolites, particularly for species containing increased numbers of phosphate groups. EID generally provided complementary fragmentation to CAD and showed extensive fragmentation with relatively evenly abundant product ions, regardless of metabolite size. However, EID fragmentation efficiency is lower than those of CAD and IRMPD.


Understanding China's growing involvement in global health and managing processes of change.
Recent years have seen a rapid change in China's global engagement and a recognition that solving global challenges will need to take the changing role of China into account. The paper discusses China's growing involvement in global health. Health is an area where there is broad agreement over global priorities and, potentially, a fertile space to build new forms of collaboration that point the way towards the adaptation of global governance to a rapidly changing context. Drawing on previous analyses of China's management of change in its domestic health reforms and interviews with a range of stakeholders in China, the UK and Switzerland, the paper argues that China's engagement in global health is developing and diversifying rapidly in response to the central government's desire to see a greater role for China in global health. This diversification is part of a pattern of change management familiar from China's domestic reform experience. Explorations underway by a range of Chinese agencies form part of a process of rapid experimentation and experiential learning that are informing China's search for (a) new global role(s). China is undergoing rapid institutional innovation and developing capacity for greater global engagement, including in health; however, substantial, recent leadership commitments make clear Chinese agencies' need for continued exploration, innovation and rapid learning. How China engages globally is of significance to the world, not just China. The challenge for China, other global actors and multilateral organisations is to incorporate new approaches into existing global governance arrangements, including for the management of global health. This will require a willingness on all sides to learn from each other and invest the effort needed to build governance arrangements appropriate for the coming decades. This is not only important as a means of protecting global public health, but also as a demonstration of how governance arrangements can be adapted to the needs of a pluralistic global order in a context of rapid change.


Acute alcohol exposure impairs fracture healing and deregulates β-catenin signaling in the fracture callus.
Alcohol abuse is a risk factor for bone damage and fracture-related complications. Through precise β-catenin signaling, canonical Wnt signaling plays a key role in fracture repair by promoting the differentiation of new bone and cartilage cells. In this study, we examined the effects of alcohol on the Wnt pathway in injured bone using a murine model of alcohol-induced impaired fracture healing. Male C57Bl/6 or T cell factor (TCF)-transgenic mice were administered 3 daily intraperitoneal doses of alcohol or saline. One hour following the final injection, mice were subjected to a stabilized, mid-shaft tibial fracture. Injured and contralateral tibias were harvested at 6, 9, or 14 days post-fracture for the analysis of biomechanical strength, callus tissue composition, and Wnt/β-catenin signaling. Acute alcohol treatment was associated with a significant decrease in fracture callus volume, diameter, and biomechanical strength at day 14 post-fracture. Histology revealed an alcohol-related reduction in cartilage and bone formation at the fracture site, and that alcohol inhibited normal cartilage maturation. Acute alcohol exposure caused a significant 2.3-fold increase in total β-catenin protein at day 6 and a significant decrease of 53 and 56% at days 9 and 14, respectively. lacZ staining in β-galactosidase-expressing TCF-transgenic mice revealed spatial and quantitative differences in Wnt-specific transcriptional activation at day 6 in the alcohol group. Days 9 and 14 post-fracture showed that acute alcohol exposure decreased Wnt transcriptional activation, which correlates with the modulation of total β-catenin protein levels observed at these time points. Acute alcohol exposure resulted in significant impairment of fracture callus tissue formation, perturbation of the key Wnt pathway protein β-catenin, and disruption of normal Wnt-mediated transcription. These data suggest that the canonical Wnt pathway is a target for alcohol in bone and may partially explain why impaired fracture healing is observed in alcohol-abusing individuals.


Dynamic Changes in Drinking Behaviour among Subpopulations of Youth during the COVID-19 Pandemic: A Prospective Cohort Study.
Youth drinking is highly heterogenous, and subpopulations representing different alcohol use patterns may have responded differently to the COVID-19 pandemic. This study examined changing patterns of alcohol use in subpopulations of the youth population over the first two years of the pandemic. We used linked survey data from 5367 Canadian secondary school students who participated in three consecutive waves of the COMPASS study between 2018/19 and 2020/21. Latent transition analysis (LTA) was used to identify patterns of alcohol use based on the frequency of drinking and frequency of binge drinking and to estimate the probability of transitioning between identified patterns. LTA identified five patterns of alcohol use each representing a unique subpopulation: abstainer, occasional drinker-no binging, occasional binge drinker, monthly binge drinker, weekly binge drinker. Probability of being engaged in binge drinking for a subpopulation of occasional drinkers pre-pandemic was 61%, which reduced to 43% during the early-pandemic period. A lower proportion of occasional binge drinkers reported moving to monthly or weekly binge drinking. Female occasional drinkers were more likely to move to binge drinking patterns during the pandemic than males. Less frequent drinking and younger students were more likely to reduce their drinking and binge drinking than more established drinkers during the COVID-19 pandemic. Understanding of heterogenous patterns of alcohol drinking and different responses to public health crises may inform future preventive programs tailored to target subpopulations more effectively.


Comparison of Effectiveness of Hiora SG Gel With Triamcinolone Acetonide Gel in Recurrent Aphthous Stomatitis.
Background The oral condition known as recurrent aphthous ulceration (RAU) or recurrent aphthous stomatitis (RAS) is very prevalent. Its etiopathogenesis is unknown; hence, symptomatic therapy is all that can be offered if it manifests clinically. Lesion care aims to minimize discomfort and the frequency of relapses by bringing active illness under local control in the affected area. The current treatment options that may have negative side effects include the use of topical and systemic steroids, antibiotics, cauterization, and laser therapy. Objectives and Importance This study aimed to compare the efficiency of HiOra SG gel with triamcinolone acetonide gel in the management of RAS. Materials and Methods Fifty individuals with RAS were recruited for the trial and randomly assigned to either group I (HiOra SG gel) or group II (0.1% triamcinolone acetonide ointment; Oraways). After each meal for a total of 10 days, those with mouth ulcers were instructed to topically administer the drugs. The clinical data were analyzed by comparing the ulcer severity scores from the first, fifth, and 10th days. Results There was a statistically significant (p = 0.001) reduction in reported pain, pain duration, and overall ulcer severity across all groups. After therapy, however, neither the HiOra gel group nor the triamcinolone group showed any discernible improvement over the other. Conclusion The present study's findings corroborate the efficacy of HiOra SG gel in the treatment of RAS when compared to triamcinolone acetonide gel (0.1%). In this trial, no patients had any negative reactions to HiOra SG gel. In the future, further studies are needed with larger samples to prove its benefits.


Reducing dehydration in residents of care homes.
Dehydration can have serious consequences for older people and is a particular problem for residents of nursing and care homes. This article, the second in a two-part series, describes how a specialist care home for people with dementia in Great Yarmouth introduced high-quality hydration care to frail residents. By involving all staff and ensuring residents take a litre of fluid by the end of a relaxed and extended breakfast, staff have reduced anxiety and aggression and created a calmer and more sociable atmosphere. This has benefitted residents, visitors and staff, and is reflected in low levels of unplanned hospital admissions and paramedic call-outs.


Puma cooperates with Bim, the rate-limiting BH3-only protein in cell death during lymphocyte development, in apoptosis induction.
The physiological role of B cell lymphoma 2 (Bcl-2) homology 3-only proteins has been investigated in mice lacking the individual genes identifying rate-limiting roles for Bim (Bcl-2-interacting mediator of cell death) and Puma (p53-up-regulated modulator of apoptosis) in apoptosis induction. The loss of Bim protects lymphocytes from apoptosis induced by cytokine deprivation and deregulated Ca++ flux and interferes with the deletion of autoreactive lymphocytes and the shutdown of immune responses. In contrast, Puma is considered the key mediator of p53-induced apoptosis. To investigate the hypothesis that Bim and Puma have overlapping functions, we generated mice lacking both genes and found that bim-/-/puma-/- animals develop multiple postnatal defects that are not observed in the single knockout mice. Most strikingly, hyperplasia of lymphatic organs is comparable with that observed in mice overexpressing Bcl-2 in all hemopoietic cells exceeding the hyperplasia observed in bim-/- mice. Bim and Puma also have clearly overlapping functions in p53-dependent and -independent apoptosis. Their combined loss promotes spontaneous tumorigenesis, causing the malignancies observed in Bcl-2 transgenic mice, but does not exacerbate the autoimmunity observed in the absence of Bim.


Sharing power and knowledge: professional and mental health consumer/survivor researchers working together in a participatory action research project.
In this article we document and reflect on the process and outcomes of consumer/survivor researchers' involvement in a community mental health research project. The study used a participatory action research approach that challenges traditional assumptions of how to conduct research. Research roles and relationships were reexamined by both professional and consumer/survivor researchers. Four values were central to the research process: consumer/survivor empowerment, supportive relationships, learning as an ongoing process, and social justice. The benefits of this value-driven approach were seen in terms of positive impacts on the lives of individual researchers and also in the quality of the research itself. Our reflections on the research process have led us to see the importance of building relationships as a means to share power and knowledge among professional and consumer/survivor researchers.


The remnants of restinga habitats in the brazilian Atlantic Forest of Rio de Janeiro state, Brazil: habitat loss and risk of disappearance.
"Restingas" (herbaceous/shrubby coastal sand-dune habitats) used to cover most of Rio de Janeiro State coast, and have suffered extensive degradation over the last five centuries. Using satellite images and field work, we identified the remaining restingas in the State, recording the factors that might cause their degradation. We used two mosaics of Landsat 7 scenes (spatial resolution 15 and 30 m) to map and evaluate preliminarly the remaining areas and conservation status. Each remnant area was checked in the field, degraded areas within it were mapped and subtracted from the remnants. We identified 21 restinga remnants totalling 105,285 ha. The largest and smallest restinga remnants were Jurubatiba (25,141 ha) and Itaipu (23 ha), respectively. We identified 14 causes of degradation. The most important were vegetation removal for housing developments, establishment of exotic plant species, change of original substrate, and selective removal of species of economic importance for the horticultural industry. All restingas had disturbed parts under strong pressure due to human activities. Due to intense habitat loss, and occurrence of endemic/threatened vertebrate species in restinga habitats, we strongly indicate the implementation of new conservation units to protect these fragile remnants. This habitat is steadily decreasing and most remnants lack legal protection. Therefore, under the current human pressure most of this unique habitat is likely to be lost from the State within the next few years.


Toll-like receptor 2 downregulates the cholesterol efflux by activating the nuclear factor-κB pathway in macrophages and may be a potential therapeutic target for the prevention of atherosclerosis.
Atherosclerosis is a chronic inflammatory disease, which is triggered by lipid retention. Toll-like receptor 2 (TLR2) is a novel target for therapeutic intervention in atherosclerosis. In addition, nuclear factor-κB (NF-κB) serves important roles in stress response and inflammation. The present study investigated whether TLR2 is involved in the activation of cholesterol efflux in macrophages by regulating the NF-κB pathway. The human monocytic THP-1 cell line and murine macrophage RAW264.7 cell line were treated with 50 µg/ml oxidized low-density lipoprotein (ox-LDL) for 48 h in order to obtain macrophage foam cells. The cholesterol efflux of the cell lines under exogenous TLR2 treatment was assessed by liquid scintillation counting. Furthermore, the protein and mRNA expression levels of ATP binding cassette transporter A1 (ABCA1), ABCG1 and scavenger receptor B1 (SR-B1) were examined by western blot and quantitative polymerase chain reaction assays, respectively. To detect the effect of NF-κB on cholesterol efflux, the cells were divided into three groups, including the control, 10 ng/ml lipopolysaccharides (LPS; 24 h) and 10 ng/ml LPS + 50 µM pyrrolidinedithiocarbamate (PDTC; 24 h) groups. The results indicated that ox-LDL induced foam cell formation in the THP-1 and RAW264.7 cells, while TLR2 significantly decreased the cholesterol efflux in dose- and time-dependent manners. Accordingly, TLR2 reduced ABCA1, ABCG1 and SR-B1 expression at the transcriptional and translational levels in a dose-dependent manner. In addition, application of PDTC (an NF-κB specific inhibitor) markedly suppressed the LPS-induced downregulation of cholesterol efflux. These data revealed that TLR2 may be involved in the activation of cholesterol efflux in macrophages by regulating the NF-κB signaling pathway.


The associations of viral and mycoplasmal antibody titers with respiratory disease and weight gain in feedlot calves.
Blood samples from 32 groups of calves (n = 700) were taken on arrival and after 28-35 days at the feedlot. Eleven groups were housed in feedlots in Ontario, and 21 groups in feedlots in Alberta. Serum antibody titers to bovine viral diarrhea virus (BVDV), bovine respiratory syncytial virus (BRSV), parainfluenza virus type 3 (PIV-3), infectious bovine rhinotracheitis virus (IBRV), Mycoplasma dispar and M. bovis, plus data on bovine corona virus (BCV) from a previous study were investigated for their association with the risk of bovine respiratory disease (BRD), and with 28-day weight change, both before and after controlling for titers to Pasteurella haemolytica and Haemophilus somnus. Exposure to IBRV and M. bovis was infrequent, and although exposure to PIV-3 was more common, none of these agents had important associations with BRD. Higher titers to BVDV, BRSV, and BCV on arrival were associated with reduced risks of BRD and increased weight gains. However, there was some variation in these relationships and higher arrival titers to BVDV and BRSV in a subset of the calves were associated with increased risks of BRD. Titer increases to BVDV were associated with a higher risk of BRD and lower weight gains. Titer increases to BRSV were not usually associated with the occurrence of BRD, but titer increases to BRSV in a subset of calves that were vaccinated against BRSV, on arrival, were associated with an elevated risk of BRD. Of all the agents studied, BVDV had the most consistent associations with elevated risk of BRD and lower weight gains. Higher BRSV arrival titers were related to lower risk of BRD and higher weight gains; in some instances titer increases to BRSV were associated with higher BRD risk. Higher titers to BCV on arrival were related to reduced risks of BRD. Practical ways of adequately preventing the negative effects of these agents are still needed.


Direct endoscopic biopsy for subepithelial tumor larger than 20 mm after removal of overlying mucosa.
An accurate diagnosis of a subepithelial tumor (SET) using endoscopic ultrasound (EUS) without tissue acquisition is difficult. Treatment plan for a SET may be influenced by endoscopic tissue diagnosis. We aimed to clarify the clinical outcomes of direct endoscopic biopsy for SET after removal of the overlying mucosa. We evaluated the medical records of 15 patients. All patients underwent direct endoscopic biopsy for a SET larger than 20 mm (involving proper muscle layer) after removal of the overlying mucosa. The rate of achieving an accurate diagnosis and the treatment decision after the procedure were evaluated. The patients' mean age was 55.1 ± 14.7 years. The patient population predominantly comprised men (9/15, 60%). The mean tumor size was 24.3 ± 7.8 mm. The mean biopsy number was 3.5 ± 1.7. No major complications occurred with the procedure. The mean procedure time was 15 ± 7.4 min. An accurate diagnosis was achieved in 93.3% of patients (14/15). The main pathological diagnoses after direct endoscopic SET biopsy were leiomyoma (33.3%, 5/15) and ectopic pancreas (33.3%, 5/15) followed by gastrointestinal stromal tumor (GIST) (13.3%, 2/15) and schwannoma (13.3%, 2/15). The treatment plan was influenced by the result of biopsy in 80% of patients (9/15), and unnecessary surgical resection was avoided. Direct endoscopic SET biopsy after removal of the overlying mucosa using an endoscopic conventional snare was a useful diagnostic tool with high diagnostic accuracy and low risk of complications.


Aesthetic dissatisfaction in patients with hand osteoarthritis and its impact on daily life.
To evaluate the nature and extent of aesthetic dissatisfaction in patients with hand osteoarthritis (OA), and to investigate its impact on daily life and its determinants. Patients with primary hand OA, consulting secondary care, underwent physical examination for the number of joints with bony joint enlargements, soft tissue swelling and deformities, and radiographs. Questionnaires were filled in to measure pain and function (Functional Index for Hand Osteoarthritis, FIHOA), dissatisfaction with the appearance of the hands and its impact (aesthetic scales from the Michigan Hand Outcomes Questionnaire, MHQ), anxiety and depression (the Hospital Anxiety and Depression Scale, HADS), and illness perceptions (the revised Illness Perception Questionnaire, IPQ-R). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated using multivariate logistic regression as measures of relative risk for dissatisfaction with appearance or its impact, adjusted for age, sex, body mass index (BMI), and joint-specific abnormalities (bony joint enlargements, deformities, or radiographic severity), self-reported pain and function. Of 247 patients (mean age 61.6 years, 88% women), 63 (26%) were aesthetically dissatisfied and 33 (13%) reported impact on daily life due to dissatisfaction. Patients with joint-specific abnormalities were at higher risk for reporting dissatisfaction. Patients who reported impact also reported more depression and negative illness perceptions, independently from joint-specific abnormalities. Hand OA patients report aesthetic dissatisfaction with their hands regularly, especially in those with joint abnormalities. This dissatisfaction has a negative impact in a small group of patients who also reported more depression and negative illness perceptions. These results indicate the influence of psychosocial factors on outcome measures in patients with hand OA.


Toxicity of targeted therapies in elderly patients.
Targeted therapies have revolutionized the treatment of cancer in recent years. However, treating elderly patients with these new biological therapies remains a challenge. Bevacizumab, a monoclonal antibody directed toward VEGF, appears to increase cardiovascular events in patients who are aged 65 years and over and increases the toxicity in these patients with lung cancer when added to chemotherapy. Owing to the less significant data available concerning the toxicity of trastuzumab and cetuximab, one cannot consider their use to be too toxic for the elderly patient. Rituximab has revolutionized the treatment of lymphomas with no apparent toxic effects in the elderly population. Small-molecule tyrosine kinase inhibitors and immunomodulators - thalidomide and lenalidomide - are emergent drugs that also appear to be efficient and safe for use in these patients. Few data are available concerning the toxicity of biological drugs in the elderly population, hence their use must be evaluated in each single case, always taking into consideration the risk-benefit ratio for the individual patient.


Polyelectrolyte-Surfactant Complexes As a Formulation Tool for Drug Delivery.
Aqueous polyelectrolyte-surfactant complexes (PESCs) are very rich with respect to their properties and the structures formed by them. By design they normally contain hydrophobic micellar surfactant aggregates complexed by long polyelectrolyte chains, thereby combining the formation of small hydrophobic domains given by the surfactant with large-scale structuring due to the presence of the polyelectrolyte chain. In addition, they contain highly polar regions of surfactant head groups in contact with polyelectrolyte, forming a shell around the micellar aggregates, which often also possesses a certain hydrophobic character. Accordingly, the ability for solubilization of water-insoluble compounds of different sorts is particularly versatile in PESCs. Their solubilization sites with very different polarities and hydrophobic characters make them very flexible in adapting to the requirements of a given drug molecule. This renders them attractive for potential applications in drug delivery. In addition, modification of the rheological properties via self-assembly and network formation can be very important in PESC applications. In the following, we discuss the structures of PESCs and their properties, with a focus on the solubilization properties. Subsequently, examples are described where PESCs have been employed in the context of drug solubilization and delivery. These comprise examples with individual aggregates, cross-linked hydrogels, and ones taking advantage of the high solubilization capacity of microemulsions.


The Effect of a Distributed Virtual Reality Simulation Training Program on Dissection Mastoidectomy Performance.
To investigate the effect on final-product performance of a distributed, virtual reality (VR) simulation training program on cadaveric dissection performance and learning curves compared with standard VR simulation training during a temporal bone course. Educational interventional cohort study. The national Danish temporal bone courses of 2016 and 2017. Postgraduate year 2 to 5 residents in otorhinolaryngology. Nine participants volunteered for additional VR simulation training (intervention) before the temporal bone course, with training blocks distributed (i.e., separated). The remaining 28 participants received standard VR simulation training during the temporal bone course (control). VR simulation and cadaveric dissection final-product performances were analyzed by blinded raters using a 26-item modified Welling Scale. Distributed VR simulation training before the temporal bone course (intervention) significantly increased dissection final-product performance by 25% compared with standard VR simulation training during the course (control) (mean scores 12.8 points versus 10.3 points, p < 0.01). Distributed and repeated VR simulation practice markedly decreased drilling time. Guidance by the simulator-integrated tutor-function significantly increased final-product performance by 2.3 points compared with nontutored procedures but at the cost of increased drilling time. Skills acquired in a VR simulation environment translate to cadaveric dissection skills and repeated and distributed VR simulation can be used to further increase performance compared with standard VR simulation training during a temporal bone course. Further dissemination of inexpensive VR simulators would allow all future temporal bone course participants to train locally before attending future centralized courses.


Concomitant carotid endarterectomy and coronary bypass surgery: should cardiopulmonary bypass be used for the carotid procedure?
With the increasing age of patients undergoing coronary artery bypass grafting (CABG), a greater number have associated clinically significant carotid disease. This study determined the morbidity and mortality for combined carotid endarterectomy (CEA)/CABG using cardiopulmonary bypass (CPB) for both procedures versus a combined approach using CPB only during CABG. Between 1993 and 2000, 65 patients (Group I) underwent combined CEA and CABG using CPB for both surgical procedures and 88 patients (Group II) underwent combined CEA and CABG using CPB only during CABG. The demographic, clinical, and carotid and coronary angiographic data were similar between groups. In Group I, 22 (33.8%) patients and 32 (36%) patients in Group II presented with contralateral carotid artery stenosis. CPB time was significantly longer in Group I, 127+/-21 minutes versus 98+/-11 minutes in Group II patients (p = 0.001). The incidence of surgical revision for bleeding and deep sternal wound infection was higher in Group I patients, 2 (3%) versus 1 (1.1%) and 5 (7.7%) versus 2 (2.2%), respectively, but not significant. Hospital mortality in Group I was 6% (4 patients) versus 5.7% (5 patients) in Group II (p = ns). Neurologic complications occurred in 4 (6%) and 5 (5.7%) patients in Group I and II, respectively (p = ns). Postoperative renal dysfunction was more common in Group I patients (22 [33.8%]) then in Group II patients 16 (19%) (p = 0.04). Of these patients, (16 [19%]) 8 (12.3%) in Group I and 6 (6.8%) in Group II required postoperative ultrafiltration (p = ns). Infectious complications were more frequent in Group I patients, 5 (7.7%) versus 2 (2.3%), but not statistically significant (p = ns). Overall actuarial survival at 1, 3, and 5 years, including all deaths, was 92%, 88%, and 82% in Group I versus 93%, 86%, and 81% in Group II (p = ns). Overall freedom from stroke at 5 years was 87.5% in Group I and 86.4% in Group II. We conclude that combined CEA/CABG using CPB only during the myocardial revascularization procedure remains the technique of choice in patients with coronary and carotid artery disease, offering better outcome in terms of perioperative morbidity than a combined CEA/CABG using CPB for both procedures.


Analysis of laser transmission and thermal effects on the inner root surface during periodontal treatment with a 940-nm diode laser in an in vitro pocket model.
The purpose of this study was to analyze thermal effects during laser-assisted periodontal treatment. An in vitro model for temperature measurements was developed to investigate different laser settings regarding pulp safety. Additionally, the influence of transmission on pulp temperature elevation was evaluated. Longitudinal root sections were irradiated with a 940-nm diode laser with 1.0 and 1.5 W in continuous wave mode. According to wall thicknesses, irradiation times were adjusted to 20 s for upper and 10 s for lower incisors, respectively. Transmission was relatively low in both upper (4.8% to 8.3% of incident power) and lower incisors (10.2% to 15.0%). Samples were embedded in a polyurethane model and six thermocouples were affixed. Regardless of dentine thickness, the middle third of the root was identified to be the area with the most heat load, where a temperature rise of 7.5°C (1.0 W) and 10.5°C (1.5 W) was registered in upper incisors. A difference of 1.5°C to 3°C was detected in lower incisors compared with uppers. All settings were safe except for 1.5 W, 20 s. Transmission affected heat generation remarkably. The proposed model provides advantages regarding heat transfer and enables for spatially resolved temperature measurements.


Decreased radioiodine uptake values without increase in urinary iodine excretion.
A total of 12842 radioiodine uptake measurements (RIU), performed for diagnostic purposes at Malmö General Hospital 1955-75, have been reviewed. In agreement with the general trend in Europe and the USA, there was a significant decrease in uptake during this period. The 24-hour RIU (mean +/- S.D.) was 51 +/- 18% in 1955, 41 +/- 17% in 1965 and 37 +/- 18% in 1975. The 3- and 48-hour uptake values, as well as the protein-bound radioiodine, fell in a parallel fashion. The fall can not be explained by an increased dietary supply of iodine, because the mean urinary excretion did not show any consistent change from 1965 to 1975, apart from a falling trend from 1967 to 1971. The cause of the decrease in thyroid iodine uptake is not elucidated by this study.


Bioanalytical method development and validation for simultaneous estimation of cefixime and dicloxacillin by RP-HPLC in human plasma.
An accurate, rapid and simple reversed-phase high performance liquid chromatography (RP-HPLC) bioanalytical method was developed and validated for simultaneous estimation of cefixime, dicloxacillin in human plasma using ezetimibe as an internal standard. The cefixime, dicloxacillin and internal standard were extracted by liquid-liquid extraction technique. Chromatographic separation is accomplished using CAPCELL PAK C18 (4.6 mm × 250 mm, 5 m) analytical column. The mobile phase consisted of phosphate buffer, acetonitrile and methanol in 42:55:03 proportions. Detection and quantification were performed by UV/Vis detection at 225 nm. The lower limit of quantification was 0.5 µg mL(-1) for both cefixime and dicloxacillin in human plasma. The calibration curves were linear over the concentration range 0.5 to 40 µg mL(-1) for both drugs in human plasma. The method was quantitatively evaluated in terms of linearity, precision, accuracy, recovery, selectivity, and stability. The method was found to be simple, convenient and suitable for the analysis of cefixime and dicloxacillin from biological fluids.


Cortical Thinning in Network-Associated Regions in Cognitively Normal and Below-Normal Range Schizophrenia.
This study assessed whether cortical thickness across the brain and regionally in terms of the default mode, salience, and central executive networks differentiates schizophrenia patients and healthy controls with normal range or below-normal range cognitive performance. Cognitive normality was defined using the MATRICS Consensus Cognitive Battery (MCCB) composite score (T = 50 ± 10) and structural magnetic resonance imaging was used to generate cortical thickness data. Whole brain analysis revealed that cognitively normal range controls (n = 39) had greater cortical thickness than both cognitively normal (n = 17) and below-normal range (n = 49) patients. Cognitively normal controls also demonstrated greater thickness than patients in regions associated with the default mode and salience, but not central executive networks. No differences on any thickness measure were found between cognitively normal range and below-normal range controls (n = 24) or between cognitively normal and below-normal range patients. In addition, structural covariance between network regions was high and similar across subgroups. Positive and negative symptom severity did not correlate with thickness values. Cortical thinning across the brain and regionally in relation to the default and salience networks may index shared aspects of the psychotic psychopathology that defines schizophrenia with no relation to cognitive impairment.


Assembly of the stator in Escherichia coli ATP synthase. Complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha.
Alpha subunit of Escherichia coli ATP synthase was expressed with a C-terminal 6-His tag and purified. Pure alpha was monomeric, was competent in nucleotide binding, and had normal N-terminal sequence. In F1 subunit dissociation/reassociation experiments it supported full reconstitution of ATPase, and reassociated complexes were able to bind to F1-depleted membranes with restoration of ATP-driven proton pumping. Therefore interaction between the stator delta subunit and the N-terminal residue 1-22 region of alpha occurred normally when pure alpha was complexed with other F1 subunits. On the other hand, three different types of experiments showed that no interaction occurred between pure delta and isolated alpha subunit. Unlike in F1, the N-terminal region of isolated alpha was not susceptible to trypsin cleavage. Therefore, during assembly of ATP synthase, complexation of alpha subunit with other F1 subunits is prerequisite for delta subunit binding to the N-terminal region of alpha. We suggest that the N-terminal 1-22 residues of alpha are sequestered in isolated alpha until released by binding of beta to alpha subunit. This prevents 1/1 delta/alpha complexes from forming and provides a satisfactory explanation of the stoichiometry of one delta per three alpha seen in the F1 sector of ATP synthase, assuming that steric hindrance prevents binding of more than one delta to the alpha3/beta3 hexagon. The cytoplasmic fragment of the b subunit (bsol) did not bind to isolated alpha. It might also be that complexation of alpha with beta subunits is prerequisite for direct binding of stator b subunit to the F1-sector.


Enhancer function of a 53-bp repetitive element in the 5' flanking region of the human neutrophil elastase gene.
Expression of the human neutrophil elastase (NE) gene is limited to the early stage of myeloid cell differentiation in bone marrow cells. While NE gene expression is controlled mainly at the transcriptional level during bone marrow cell differentiation, the mechanism of transcriptional control is not fully understood. One motif of interest in the 5' flanking region of the gene is the six tandem repeats of a 53-bp nucleotide sequence (REP53) containing a potential binding site for a basic helix-loop-helix protein located at -1032 to -716. The REP53 sequence can function as a non-cell specific transcriptional enhancer which is capable of augmenting heterologous promoter activity. When the single REP53 element was inserted into the pAZ1037 chloramphenicol acetyltransferase (CAT) expression vector immediately upstream of the chicken beta-actin promoter in either normal or inverted orientation and used to transfect K-562 erythroleukemia or HeLa cervical carcinoma cells, these modified vectors achieved 2 to 3-fold higher CAT activity than the parental pAZ1037 vector irrespective of orientation of the REP53.


Abnormal Semen in Male Partners of Infertile Couples at HRH Maha Chakri Sirindhorn Medical Center.
To determine the pattern of abnormal semen and its associate factor in male partners of infertile couples. This research was a descriptive study. The men who attended our infertility clinic during January 2008 through December 2008 were included in the present study. All of the semen samples were analysed with standard technique using the World Health Organization (1999) protocol. The associate factors for abnormal semen were collected and analyzed. A total of 75 men who had official semen report, sixty-four men (85.3%) were referred for primary infertility. The mean patients' age was 35.6 ± 5.8 years. The mean duration of infertility of couples was 3.6 ± 2.6 years. All of these subjects had abnormal semen analysis; the most common finding was astheno-teratozoospermia in 84%. Eight men (10.7%) had oligo-astheno-teratozoospermia. Three men (4%) had teratozoospermia alone. The two most common associated factors were heavy exercise and alcoholic drinking. Male factor infertility shares a pivotal role in infertile couples. Combine abnormal sperm motility and morphology group was very common. Further studies need to be carried out to explore the cause of this abnormality.


Phylogenetic and biochemical evidence for a secondary structure model of a small cytoplasmic RNA from Bacilli.
Small cytoplasmic RNA (scRNA; 271 nucleotides) is an abundant, stable RNA identified in the Gram-positive eubacterium Bacillus subtilis. Several findings suggest an important role of scRNA in protein biosynthesis: it shares structural and biochemical features with the Escherichia coli 4.5S RNA (114 nucleotides), a molecule known to be involved in this process, and it can complement the essential function of 4.5S RNA in vivo. The common apical hairpin motif of scRNA and 4.5S RNA also exists in eukaryotic 7SL RNA, the RNA component of the signal recognition particle. To elucidate the higher-order structure of scRNA, we have combined a phylogenetic approach with a biochemical one. The sequence of scRNA from a thermophilic relative of B. subtilis, Bacillus stearothermophilus, was determined and compared with the B. subtilis scRNA. In addition, the solution structure of B. stearothermophilus scRNA was probed with single- and double-strand-specific nucleases. Both types of analysis support a secondary structure model for scRNA that strongly resembles 4.5S RNA and respective parts of 7SL RNA. The results provide further evidence for the suggestion of a functional relationship between these RNAs.


Role of macrophages in liver cirrhosis: fibrogenesis and resolution.
At present, chronic liver disease accounts for approximately 2 million deaths per year worldwide. Liver injury induces a series of events causing inflammation. Chronic inflammation ends in liver fibrosis. A stage of fibrinolysis occurs on stopping insult. Kupffer cells play their role to initiate inflammatory responses, while infiltrating monocyte-derived macrophages have a role both in chronic inflammation and fibrosis and in fibrosis resolution. Ly-6C high expressing monocytes act during fibrogenesis, while Ly-6C low expressing monocytes are restorative macrophages which promote resolution of fibrosis after end of the injury. Recent studies have identified new phenotypes, such as metabolically activated M, oxidized, which may have a role in fatty liver diseases.


Characteristics and survival of patients with Ebola virus infection, malaria, or both in Sierra Leone: a retrospective cohort study.
The 2014-15 Ebola virus disease (EVD) epidemic strained health systems in west Africa already overburdened with other diseases, including malaria. Because EVD and malaria can be difficult to distinguish clinically, and rapid testing was not available in many Ebola Treatment Units (ETUs), guidelines recommended empirical malaria treatment. Little is known, however, about the prevalence and characteristics of patients entering an ETU who were infected with malaria parasites, either alone or concurrently with Ebola virus. Data for sociodemographics, disease characteristics, and mortality were analysed for patients with suspected EVD admitted to three ETUs in Sierra Leone using a retrospective cohort design. Testing for Ebola virus was done by real-time PCR and for malaria by a rapid diagnostic test. Characteristics of patients were compared and survival analyses were done to evaluate the effect of infection status on mortality. Between Dec 1, 2014, and Oct 15, 2015, 1524 cases were treated at the three ETUs for suspected EVD, of whom 1368 (90%) had diagnostic data for malaria and EVD. Median age of patients was 29 years (IQR 20-44) and 715 (52%) were men. 1114 patients were EVD negative, of whom 365 (33%) tested positive for malaria. Of 254 EVD positive patients, 53 (21%) also tested positive for malaria. Mortality risk was highest in patients diagnosed with both EVD and malaria (35 [66%] of 53 died) and patients diagnosed with EVD alone (105 [52%] of 201 died). Compared with patients presenting to ETUs without malaria or EVD, mortality was increased in the malaria positive and EVD positive group (adjusted hazard ratio 9·36, 95% CI 6·18-14·18, p<0·0001), and the malaria negative and EVD positive group (5·97, 4·44-8·02, p<0·0001), but reduced in the malaria positive and EVD negative group (0·37, 0·20-1·23, p=0·0010). Malaria parasite co-infection was common in patients presenting to ETUs and conferred an increased mortality risk in patients infected with Ebola virus, supporting empirical malaria treatment in ETUs. The high mortality among patients without EVD or malaria suggests expanded testing and treatment might improve care in future EVD epidemics. International Medical Corps.


Reliability of the ALPHA health-related fitness test battery in adolescents with Down syndrome.
The Assessing Levels of Physical Activity (ALPHA) health-related fitness test battery is a set of reliable, valid, and feasible tests to assess health-related physical fitness in children and in adolescents. The aim of this study was to examine the reliability of this battery in adolescents with Down syndrome (DS). The extended ALPHA health-related fitness test battery was performed twice within 1 month in 17 apparently healthy adolescents, aged 12-18 years, with DS who had an intelligence quotient ≥ 35. Intraclass correlation coefficient (ICC) was used to determinate test-retest reliability, and nonparametric Wilcoxon signed rank test was used to compare mean differences between measurements. With the exception of subscapular skinfold test, which obtained a moderate agreement (ICC = 0.64), all tests had a very high reliability: the 20-m shuttle-run test (ICC = 0.86), the right handgrip strength test (ICC = 0.86), the left handgrip strength test (ICC = 0.86), the standing broad jump test (ICC = 0.85), body mass index (ICC = 0.95), waist circumference (ICC = 0.98), triceps skinfold (ICC = 0.85), and the 4 × 10-m shuttle-run test (ICC = 0.92). There were no significant differences (all p > 0.05) in any of the tests. The ALPHA health-related fitness battery is reliable for measuring health-related components of fitness in adolescents with DS.


Integrating motivational interviewing with cognitive behavioural therapy for anxiety disorders, depression and co-morbid unhealthy lifestyle behaviours: a randomised controlled pilot trial.
A substantial proportion of patients receiving cognitive behavioural therapy (CBT) do not achieve remission, and drop-out is considerable. Motivational interviewing (MI) may influence non-response and drop-out. Previous research shows that MI as a pre-treatment to CBT produces moderate effects compared with CBT alone. Studies integrating MI with CBT (MI-CBT) are scarce. To test the feasibility of MI-CBT in terms of therapist competence in MI and various participant measures, including recruitment and retention. In addition, separate preliminary evaluations were conducted, exploring the effects of CBT alone for anxiety disorders and depression, and of MI-CBT for anxiety disorders, depression and unhealthy lifestyle behaviours. Using a randomised controlled parallel trial design, participants were recruited in routine psychiatric care and allocated to CBT alone or MI-CBT. Means in feasibility measures and within-condition Hedges' g effect sizes in treatment outcome measures were calculated. Authors were not blind to treatment allocation, while independent raters were blind. Seventy-three patients were assessed for eligibility, and 49 were included. Participant perceptions of treatment credibility, expectancy for improvement, and working alliance were similar for both conditions. Overall, effect sizes were large across outcome measures for both conditions, including anxiety and depressive symptoms and functional impairment. However, therapists did not acquire sufficient competence in MI and the drop-out rate was high. MI-CBT proved feasible in some respects, but the present study did not support the progression to a randomised controlled trial designed to assess the effectiveness of MI-CBT. Additional pilot studies are needed.


[Biocermics in rat experiments (preliminary report)].
Bioactive ceramics in the shape of small plates was implanted into the femoral diaphysis of rats. The specimens were examined 2 months later by optical and mechanical methods for their behaviour of incorporation into the tissues. The composition of materials, the technique of implantation, the methods of histological preparation and the examination of adhesive resistance are described. The inadequacy of current methods of examination and their replacement by better ones is pointed out.


Grease-gun injury of the orbit: two cases report and literature review.
The grease-guns injury is an uncommon injury to the orbit. We present the twelfth and thirteenth cases of grease-gun injury to the orbit to be reported in the English language literature since 1964. Here we discus and review the presentation, investigation, and treatment of this unusual trauma. Case 1 was a 29-year-old man who presented 1 day after a grease-gun injury of the left orbit with severe pain, marked periorbital swelling, and proptosis. Computed tomography (CT) revealed penetration of grease into his left orbit. Following surgical removal, proptosis decreased. The limitation of extraocular movement and loss of visual acuity to finger count was discovered after the initial surgery. Motility gradually returned. Visual acuity recovered after phacoemulsification, capsular tension ring and intraocular lens implantation for traumatic cataract and subluxation. Case 2 was a 6-year-old boy who was referred 2 months after a grease-gun injury for worsening swelling with sinus, necrosis and slight ptosis of the upper left eyelids. This is a case of orbital chronic inflammation from grease-gun injuries masquerading as orbital cellulitis. The imaging findings of CT and magnetic resonance imaging (MRI) are not typical. Surgical exploration and debridement was inevitable and actually relieved the symptoms. Grease-gun injuries can damage the orbit in different degrees. Careful history inquiry and taking is important to establish the diagnosis. Imaging examinations using CT or MRI are helpful to determine depth of trauma and foreign bodies in the orbit at diagnosis. We suggest that surgical exploration and debridement is a key step in the management.


Targeted Mitochondrial Fluorescence Imaging-Guided Tumor Antimetabolic Therapy with the Imprinted Polymer Nanomedicine Capable of Specifically Recognizing Dihydrofolate Reductase.
As we all know, inhibiting the activity of dihydrofolate reductase (DHFR) has always been an effective strategy for folate antimetabolites to treat tumors. In the past, it mainly relied on chemical drugs. Here, we propose a new strategy, (3-propanecarboxyl)triphenylphosphonium bromide (CTPB)-modified molecularly imprinted polymer nanomedicine (MIP-CTPB). MIP-CTPB prepared by imprinting the active center of DHFR can specifically bind to the active center to block the catalytic activity of DHFR, thereby inhibiting the synthesis of DNA and ultimately inhibiting the tumor growth. The modification of CTPB allows the nanomedicine to be targeted and enriched in mitochondria, where DHFR is abundant. The confocal laser imaging results show that MIP-CTPB can target mitochondria. Cytotoxicity experiments show that MIP-CTPB inhibits HeLa cell proliferation by 42.2%. In vivo experiments show that the tumor volume of the MIP-CTPB-treated group is only one-sixth of that of the untreated group. The fluorescent and paramagnetic properties of the nanomedicine enable targeted fluorescence imaging of mitochondria and T2-weighted magnetic resonance imaging of tumors. This research not only opens up a new direction for the application of molecular imprinting, but also provides a new idea for tumor antimetabolic therapy guided by targeted mitochondrial imaging.


Effects of fraxetin on glutathione redox status.
We have evaluated the effects of an oral treatment of mice with fraxetin (25 mg/kg for 30 days) on the glutathione system (GSH, GSSG, and GSSG/GSH ratio as stress index), glutathione reductase (GR) and glutathione peroxidase (GPx) in liver supernatants from male C57BL/6J mice (18-month old). A significant antioxidant effect in vivo was found under this treatment by a decrease in the GSSG/GSH ratio and an increased activity of GR compared with the control mice. GSSG rate and GSSG/GSH ratio were correlated with the decline of GPx++ activity. Our results of increased GR activity could be considered as a supercompensation in glutathione redox status that involves a decrease in the accumulation of GSSG, as well as, in GSSG/GSH ratio. Finally, we suggest that this possible mechanism of supercompensation could lead to an enhancement in the average life span.


Demonstration of double-chambered right ventricle on myocardial perfusion SPECT.
A 19-year-old man with a double-chambered right ventricle (DCRV) and an associated ventricular septal defect was admitted to the hospital for surgical correction. Preoperative study of myocardial perfusion with Tc-99m tetrofosmin SPECT depicted the two chambers of the right ventricle. There was a substantial differential in the radioactive uptake between these two chambers. The inflow and outflow chambers with different peak-pressures (94 and 18 mm Hg) showed different uptakes reflecting the pressure difference, which was intense in the inflow chamber and weak in the outflow.


Effect of Deep Sedation on Mechanical Power in Moderate to Severe Acute Respiratory Distress Syndrome: A Prospective Self-Control Study.
Mechanical power (MP) is a parameter for assessing ventilator-induced lung injury (VILI) in patients with acute respiratory distress syndrome (ARDS). Deep sedation inhibits the respiratory center and reduces the excessive spontaneous breathing in ARDS patients, thereby reducing transpulmonary pressure (Ptp) and lung injury. However, the effect of sedation on MP in ARDS patients is not yet clear. Therefore, the purpose of this study was to investigate the effect of deep sedation on MP in ARDS patients. Patients with moderate to severe ARDS who required mechanical ventilation were considered. Different degrees of sedation were performed on patients in three stages after 24 hours of mechanical ventilation. The three stages are as follows: stage 1 (H+3): 0 to 3 hours of sedation; patients' Ramsay score was 2-3 to obtain mild sedation; stage 2 (H+6): 4 to 6 hours of sedation; the sedation depth was adjusted to 5-6 points; and stage 3 (H+9): 7 to 9 hours of sedation; the sedation depth was adjusted to 2-3 points. Under deep sedation (H+6), MP, respiratory rate (RR), and Ptp were significantly lower than the ones in the patients under mild sedation (H+3) (all P < 0.01) although PaO2 /FiO2 (P/F) and static lung compliance (Cst) were significantly higher (both P < 0.01). However, no significant difference in the above parameters was observed between H+3 and H+9. Correlation analysis showed that ΔMP was significantly and positively correlated with ΔRR and ΔPtp (both P < 0.001), while no correlation was observed neither between ΔMP and ΔCst nor between ΔMP and ΔP/F. The 28-day Kaplan-Meier survival curve showed the occurrence of 19 deaths, and the overall survival rate was 63.46%. The survival rate was 53.12% in the high-MP (HMP) group and 80.95 in the low-MP (LMP) group (P < 0.05). In conclusion, deep sedation significantly reduced MP in patients with moderate to severe ARDS, thereby reducing the occurrence of VILI. In addition, MP monitoring in deep sedation predicted the 28-day survival of patients with moderate to severe ARDS.


Cochlear implantation under local anaesthesia - Our experience and a validated patient satisfaction questionnaire.
Cochlear implantation (CI) under local anaesthetic (LA) has previously been shown to be a successful and safe option for a specific group of patients (e.g. elderly and significant co-morbidity). We aim to discuss our practice and obtain qualitative information about patient experience from our cohort of patients at the Yorkshire Auditory Implant Service (YAIS). Retrospective chart review to include demographics, co-morbidities and physiological parameters were recorded and used to calculate P-POSSUM (Portsmouth Physiological and Operative Severity Score for the enumeration of Mortality and Morbidity) scores. The Iowa Satisfaction with Anaesthesia Scale (ISAS) questionnaire was distributed to all patients who received CI under LA and subsequently analysed. Seven patients received CI under LA at YAIS. This included five males and two females. The mean age was 79 years (range 26 -93). The mean P-POSSUM mortality and morbidity for this cohort was 2.4 and 34.9%, respectively. The average ISAS score was +1.72 (where range of -3 is completely dissatisfied and +3 is completely satisfied). We discuss our cohort and show that patients receiving CI have a favourable experience when LA is used. CI under LA is a viable and safe option for more elderly patients and those who are deemed at high risk of morbidity or mortality associated with a general anaesthetic. The data regarding validated patient experience obtained from this study can be used to help counsel patients that may be offered CI under LA.


Transient temperature rise due to ultrasound absorption at a bone/soft-tissue interface.
Thermal effects due to high ultrasound absorption in bone pose an ongoing safety issue. Of considerable concern is the heating of the soft tissue adjacent to the bone surface. Mathematical models can be useful in predicting the transient temperature near the interface during insonation. This paper develops a model that provides the temperature field in terms of simple expressions that convey the functional dependence of the material properties, and are easily incorporated into standards and ultrasound machine software, yet are able to incorporate the material properties of both bone and soft tissue. The model contains an asymptotic theory based upon a "high-attenuation" assumption: the distance diffused by heat over the time of interest is large compared to the ultrasound attenuation length. Model predictions of temperature rise and location of maximum temperature were in close agreement with finite-element calculations, using parameters appropriate for radiation-force imaging and focused-ultrasound surgery.


[Construction and homologous detection of a DNA plasmid library specific for Z chromosome of quail].
A simple method was used to adapt a standard light microscope for the collection of quail Z chromosomes from mitotic-metaphase spreads. The microisolated chromosomes were subjected to proteinase K treatment in a collection drop to release DNA, which was then amplified using a degenerate oligonucleotide-primed PCR (DOP-PCR) strategy. Size distributions of the PCR products were analyzed by agarose gel electrophoresis, and smears of DNA revealed that ranged in size from 200-1 400 bp, without any evidence of preferential amplification. The second-round PCR products were cloned into pBluescript plasmids to construct a Z chromosome-specific DNA library. The size range of the cloned inserts was 200-1 400 bp. Using inserted fragments from the library as probes, chromosome painting was performed on quail chromosomes. The results showed that Z chromosomes of quail were completely covered by strong signals and there were little signals on other chromosomes. It was indicated that inserted DNA of the library was specific to the Z chromosome of quail. The library can be used as chromosome painting probe to detect conserved syntenic groups on the chromosomes of other related species and study mechanisms of sex-chromosomes evolution in birds.


Melanoma cells undergo aggressive coalescence in a 3D Matrigel model that is repressed by anti-CD44.
Using unique computer-assisted 3D reconstruction software, it was previously demonstrated that tumorigenic cell lines derived from breast tumors, when seeded in a 3D Matrigel model, grew as clonal aggregates which, after approximately 100 hours, underwent coalescence mediated by specialized cells, eventually forming a highly structured large spheroid. Non-tumorigenic cells did not undergo coalescence. Because histological sections of melanomas forming in patients suggest that melanoma cells migrate and coalesce to form tumors, we tested whether they also underwent coalescence in a 3D Matrigel model. Melanoma cells exiting fragments of three independent melanomas or from secondary cultures derived from them, and cells from the melanoma line HTB-66, all underwent coalescence mediated by specialized cells in the 3D model. Normal melanocytes did not. However, coalescence of melanoma cells differed from that of breast-derived tumorigenic cell lines in that they 1) coalesced immediately, 2) underwent coalescence as individual cells as well as aggregates, 3) underwent coalescence far faster and 4) ultimately formed long, flat, fenestrated aggregates that were extremely dynamic. A screen of 51 purified monoclonal antibodies (mAbs) targeting cell surface-associated molecules revealed that two mAbs, anti-beta 1 integrin/(CD29) and anti-CD44, blocked melanoma cell coalescence. They also blocked coalescence of tumorigenic cells derived from a breast tumor. These results add weight to the commonality of coalescence as a characteristic of tumorigenic cells, as well as the usefulness of the 3D Matrigel model and software for both investigating the mechanisms regulating tumorigenesis and screening for potential anti-tumorigenesis mAbs.


Combination Therapy with TCM Preparation Kumu Injection and Azithromycin against Bacterial Infection and Inflammation: In Vitro and In Vivo.
Azithromycin (AZM) is one of the most common broad-spectrum antibiotics. However, drug resistance is increasing and combination therapy has attracted great attention. AZM is usually combined with traditional Chinese medicine (TCM) preparations with heat-clearing and detoxifying effects, including Kumu injection (KM) made from Picrasma quassioides (D. Don) Benn. The present study aimed to investigate synergistic antimicrobial and anti-inflammatory activities of KM plus AZM with the aim of understanding the mechanism of clinical efficacy of combination regimens. Seven common bacterial clinical isolates and LPS-induced RAW 264.7 cells were used for assay of in vitro potency. The minimum inhibitory concentration (MIC) was determined for each drug, followed by synergy testing through the checkerboard method and fractional inhibitory concentration index (FICI) for quantifying combined antibacterial effects. The rat model of Klebsiella pneumoniae-induced pneumonia was developed and subjected to various drug treatments, namely, AZM, KM, or AZM plus KM, intravenously administered at 75 mg/kg once a day for one week. The combination effects then were evaluated according to pharmacodynamics and pharmacokinetic assessments. KM-AZM combination synergistically inhibits in vitro growth of all the test standard strains except Pseudomonas aeruginosa and also the drug-resistant strains of Staphylococcus aureus, Streptococcus pneumoniae, Shigella dysenteriae, Klebsiella pneumoniae, and Escherichia coli. Despite an additive effect against NO, KM plus AZM at an equal dose could synergistically suppress overrelease of the inflammatory cytokines TNF-α and IL-6 by LPS-induced RAW 264.7 cells. The combination significantly inhibited the proliferation of K. pneumoniae in the rat lungs, mainly by inactivating MAPKs and NF-κB signaling pathways. KM-AZM combination caused a onefold increase in apparent distribution volume of AZM, along with a significant decrease of AZM level in the livers and heart for pharmacokinetics. KM-AZM combination displayed synergistic antibacterial and anti-inflammatory effects beneficial to the therapeutic potential against bacterial infection.


Agent-patient similarity affects sentence structure in language production: evidence from subject omissions in Mandarin.
Interference effects from semantically similar items are well-known in studies of single word production, where the presence of semantically similar distractor words slows picture naming. This article examines the consequences of this interference in sentence production and tests the hypothesis that in situations of high similarity-based interference, producers are more likely to omit one of the interfering elements than when there is low semantic similarity and thus low interference. This work investigated language production in Mandarin, which allows subject noun phrases to be omitted in discourse contexts in which the subject entity has been previously mentioned in the discourse. We hypothesize that Mandarin speakers omit the subject more often when the subject and the object entities are conceptually similar. A corpus analysis of simple transitive sentences found higher rates of subject omission when both the subject and object were animate (potentially yielding similarity-based interference) than when the subject was animate and object was inanimate. A second study manipulated subject-object animacy in a picture description task and replicated this result: participants omitted the animate subject more often when the object was also animate than when it was inanimate. These results suggest that similarity-based interference affects sentence forms, particularly when the agent of the action is mentioned in the sentence. Alternatives and mechanisms for this effect are discussed.


Protein kinase C association with the retinal cytoskeleton and phosphorylation of vimentin.
Protein kinase C plays an important role in regulation of the cytoskeleton. We found that protein kinase C activity is associated with the retinal cytoskeleton, and that it catalyses the stoichiometric phosphorylation of two cytoskeletal proteins, with apparent molecular masses of 56 kDa and 100 kDa. The 56-kDa substrate was identified as vimentin on the basis of its apparent molecular mass, pI, solubility, immunoreactivity, pattern of proteolysis by Lys-C and a partial amino acid sequence. Immunomicroscopy was consistent with previous reports that in the retina vimentin has the unusual property of being present in neuronal cells--horizontal cells--as well as non-neuronal cells. The characteristics of protein kinase C phosphorylation of vimentin that was enriched in neuronal vimentin were determined. Hyperactivation of protein kinase C by treatment of retinas with phorbol myristate acetate resulted in the phosphorylation of vimentin in situ, indicating that the phosphorylation is physiologically relevant. In vitro, purified retinal protein kinase C catalysed the incorporation of nearly 2 mol phosphate per mole of monomeric vimentin. The phosphorylation was highly dependent on the presence of phosphatidylserine. Thus, protein kinase C functions in the retinal cytoskeleton, where a major role is in the modification of vimentin. The characterization of the phosphorylation of outer retinal vimentin by protein kinase C provides a basis for further studies on the regulation and function of this cytoskeletal element.


Maladaptive denial of physical illness: a useful new "diagnosis".
Denial of physical illness and/or refusal of treatment are critical issues in the practice of medicine. A previous article proposed DSM-IV consider a new diagnosis for a subgroup of patients who refuse treatment, i.e., maladaptive denial of physical illness [1]. It is necessary to be able to use this form of denial as a diagnosis rather than invoke the term denial as merely a mental mechanism. This is a report of a prospective descriptive study of psychiatric consultations for medical inpatients who deny that they are ill or who refuse treatment. In order to investigate the utility of this proposed diagnosis we conducted a one year study of all psychiatric consultations at a community hospital in Manhattan, New York. The diagnosis of maladaptive denial of physical illness was made in 2.5 percent of 317 psychiatric consultations. The patients did not fit into other DSM-III-R or DSM-IV categories. We suggest a clarification of the concept of denial for use with medically ill patients. The findings in this study demonstrate that the current categories in DSM-IV do not provide physicians with a diagnosis that describes this particular type of pathological denial of illness.


An Artificial Intelligence-Based Bio-Medical Stroke Prediction and Analytical System Using a Machine Learning Approach.
Stroke-related disabilities can have a major negative effect on the economic well-being of the person. When left untreated, a stroke can be fatal. According to the findings of this study, people who have had strokes generally have abnormal biosignals. Patients will be able to obtain prompt therapy in this manner if they are carefully monitored; their biosignals will be precisely assessed and real-time analysis will be performed. On the contrary, most stroke diagnosis and prediction systems rely on image analysis technologies such as CT or MRI, which are not only expensive but also hard to use. In this study, we develop a machine learning algorithm for the prediction of stroke in the brain, and this prediction is carried out from the real-time samples of electromyography (EMG) data. The study uses synthetic samples for training the support vector machine (SVM) classifier and then the testing is conducted in real-time samples. To improve the accuracy of prediction, the samples are generated using the data augmentation principle, which supports training with vast data. The simulation is conducted to test the efficacy of the model, and the results show that the proposed classifier achieves a higher rate of classification accuracy than the existing methods. Furthermore, it is seen that the rate of precision, recall, and f-measure is higher in the proposed SVM than in other methods.


Relation between prenatal maternal mood and anxiety and neonatal health.
To examine the relation between the mood and anxiety of pregnant, psychiatrically treated women and neonatal health outcomes after birth. We prospectively assessed 46 women treated with psychotropic medications for anxiety and depression during pregnancy. We compared measures of maternal mental health with infant outcomes, in particular, the outcomes of infants with symptoms of poor neonatal adaptation. The mothers of babies who demonstrated poor neonatal adaptation reported higher levels of anxiety and depression at study entry than did the mothers of healthy babies. This relation was not related to the presence or absence of treatment with clonazepam, an anxiolytic used to treat symptoms of anxiety. Further, increased psychiatric comorbidity in the mother was associated with a greater likelihood of transient symptoms in the newborn. Despite psychiatric treatment, the intensity and degree of comorbid symptoms appear to be related to poor transient neonatal health outcome. Our data suggest that, in addition to the impact of pharmacologic factors, maternal psychiatric status influences infant outcomes.


Breast cancer in Latin America and the Caribbean.
As recently as two decades ago breast cancer was not a significant public health concern in Latin America and the Caribbean (LAC). However, mortality rates from breast cancer have been increasing for at least 40 years in most LAC countries. Socioeconomic development and consequent changes in reproductive behaviors over the past 50 years are thought to have contributed to the increased risk of breast cancer. Socioeconomic development has also increased women's health awareness and therefore the demand for quality services. In industrialized countries, screening and widely available, high-quality treatment protocols are being implemented as the main strategy for breast cancer control. Studies show that out of three available screening methods (mammography, clinical breast examination, and breast self-examination), only mammography for women 50-69 years of age has been effective at reducing mortality, and has done so by an estimated 23%. While there is much controversy about the benefits and cost-effectiveness of mammography screening for women aged 40-49, some countries, including Australia, the United States of America, and four European nations, recommend that physicians assess the need for it on an individual basis. A survey that we conducted of LAC countries shows that most of their breast cancer screening policies are not justified by available scientific evidence. Moreover, as seen by relatively high mortality/incidence ratios, breast cancer cases are not being adequately managed in many LAC countries. Before further developing screening programs, these countries need to evaluate the feasibility of designing and implementing appropriate treatment guidelines and providing wide access to diagnostic and treatment services. Given the relevance of breast cancer in Latin America and the Caribbean today, it is crucial that both women and health care providers have access to up-to-date information on which to base their decisions.


Near-Optimal Foraging in the Pacific Cicada Killer Sphecius convallis Patton (Hymenoptera: Crabronidae).
This study evaluated foraging effectiveness of Pacific cicada killers (Sphecius convallis) by comparing observed prey loads to that predicted by an optimality model. Female S. convallis preyed exclusively on the cicada Tibicen parallelus, resulting in a mean loaded flight muscle ratio (FMR) of 0.187 (N = 46). This value lies just above the marginal level, and only seven wasps (15%) were below 0.179. The low standard error (0.002) suggests that S. convallis is the most ideal flying predator so far examined in this respect. Preying on a single species may have allowed stabilizing selection to adjust the morphology of females to a nearly ideal size. That the loaded FMR is slightly above the marginal level may provide a small safety factor for wasps that do not have optimal thorax temperatures or that have to contend with attempted prey theft. Operational FMR was directly related to wasp body mass. Smaller wasps were overloaded in spite of provisioning with smaller cicadas, while larger wasps were underloaded despite provisioning with larger cicadas. Small wasps may have abandoned larger cicadas because of difficulty with carriage.


Knowledge, attitudes and commitment toward organ donation among nursing students in Hong Kong.
Organ donation is the major component for transplant programs; however, the rate of organ donation is relatively low in Asia. Therefore, understanding the attitude and knowledge of individuals that affect their willingness to commit as an organ donor is crucial to develop effective educational programs that raise public awareness and commitment toward organ donation. The current study aims to identify the knowledge level, attitude, and commitment toward organ donation among nursing students in a local university. A questionnaire was developed and distributed to all full-time nursing students of undergraduate and master programs in a university at Hong Kong. A total of 362 students completed the questionnaire, including 87 males and 257 females. The mean age of the students was 22.6 years. A total of 147 students (40.6%) had registered for organ donation. Students on average could correctly answer 23.7 out of 33 questions (71.8%) regarding their knowledge on organ donation and transplantation. With regard to attitude toward organ donation, students obtained a mean score of 70.2. Univariate analysis revealed that year of study, religion, and attitude were significantly associated with commitment toward organ donation. In logistic regression analysis, year of study (odds ratio [OR] for year 2, 1.961, 95% confidence interval [CI], 1.006-3.824; OR for year 3, 6.915, 95% CI, 2.835-16.868; and OR for year 4, 4.845, 95% CI, 2.071-11.334) and attitude (OR, 1.087, 95% CI, 1.049-1.126) were significantly associated with commitment toward donation after adjusting the age, gender, and study program. Attitude and year of study were strongly correlated with commitment toward organ donation; therefore, educational or promotional materials should be provided to improve the attitude of students toward organ donation.


Recent Advances of Triglyceride Catalytic Pyrolysis via Heterogenous Dolomite Catalyst for Upgrading Biofuel Quality: A Review.
This review provides the recent advances in triglyceride catalytic pyrolysis using heterogeneous dolomite catalysts for upgrading biofuel quality. The production of high-quality renewable biofuels through catalytic cracking pyrolysis has gained significant attention due to their high hydrocarbon and volatile matter content. Unlike conventional applications that require high operational costs, long process times, hazardous material pollution, and enormous energy demand, catalytic cracking pyrolysis has overcome these challenges. The use of CaO, MgO, and activated dolomite catalysts has greatly improved the yield and quality of biofuel, reducing the acid value of bio-oil. Modifications of the activated dolomite surface through bifunctional acid-base properties also positively influenced bio-oil production and quality. Dolomite catalysts have been found to be effective in catalyzing the pyrolysis of triglycerides, which are a major component of vegetable oils and animal fats, to produce biofuels. Recent advances in the field include the use of modified dolomite catalysts to improve the activity and selectivity of the catalytic pyrolysis process. Moreover, there is also research enhancement of the synthesis and modification of dolomite catalysts in improving the performance of biofuel yield conversion. Interestingly, this synergy contribution has significantly improved the physicochemical properties of the catalysts such as the structure, surface area, porosity, stability, and bifunctional acid-base properties, which contribute to the catalytic reaction's performance.


Sympathetic skin response (SSR) in Crohn disease: a pilot study.
Peripheral neuropathy is one of the most frequently reported neurological extra-intestinal manifestations of the Crohn disease. Former studies have showed sympathetic neuropathy as early manifestation of CD by physical tests. The aim of this study is to examine sympathetic neuropathy in CD by using sympathetic skin response (SSR). We performed SSR on 6 Patients (4 male, 2 female) that were diagnosed as CD. Their age was between 26 till 68 years with the mean of (43.3 +/- 17.1) years. The duration of their disease was at least 4 years (mean: 9.0 +/- 8.4) and none of the patients had any symptoms or signs related to autonomic nervous system dysfunction. Hand and foot latencies in CD patients were prolonged relative to controls and the difference of hand latencies was statistically significant. Two patients demonstrated total abnormal results. In conclusion, there is some sub-clinical sympathetic dysfunction in CD patient. This suggests that SSR can be useful in detecting early autonomic changes in these patients.


Dose-Finding Quantitative 18F-FDG PET Imaging Study with the Oral Pan-AKT Inhibitor GSK2141795 in Patients with Gynecologic Malignancies.
AKT (a serine/threonine-specific protein kinase) regulates many cellular processes contributing to cytotoxic drug resistance. This study's primary objective examined the relationship between GSK2141795, an oral, pan-AKT inhibitor, and (18)F-FDG PET markers of glucose metabolism in tumor tissue to determine whether (18)F-FDG PET could be used to guide personalized dosing of GSK2141795. Biomarker analysis of biopsies was also undertaken. Twelve patients were enrolled in 3 cohorts; all underwent dynamic (18)F-FDG PET scans and serial pharmacokinetic sampling at baseline, week 2, and week 4 with tumor biopsies before treatment and at week 4. Response was evaluated by RECIST v1.1 and Gynecologic Cancer Intergroup criteria. Biopsy samples were analyzed for mutations and protein expression. GSK2141795 did not significantly influence blood glucose levels. No dose-response relationship was observed between GSK2141795 pharmacokinetics and (18)F-FDG PET pharmacodynamic measures; however, an exposure-response relationship was seen between maximum drug concentrations and maximal decrease in (18)F-FDG uptake in the best-responding tumor. This relationship also held for pharmacokinetic parameters of exposure and 1,5-anhydroglucitol (a systemic measure of glucose metabolism). Phospho-AKT upregulation at week 4 in biopsies confirmed AKT inhibition by GSK2141795. Single-agent activity was observed with a clinical benefit rate of 27% (3/11) and 30% (3/10) CA125 response in the study's platinum-resistant ovarian patients. AKT pathway activation by PIK3CA/PIK3R1 mutation did not correlate with clinical activity, whereas RAS/RAF pathway mutations did segregate with resistance to AKT inhibition. GSK2141795 demonstrated an exposure-response relationship with decreased (18)F-FDG uptake and is active and tolerable. This study's design integrating (18)F-FDG PET, pharmacokinetics, and biomarker analyses demonstrates the potential for clinical development for personalized treatment.


Nocturnal enuresis: A topic review and institution experience.
The objective is to provide a review of nocturnal enuresis (NE), including its epidemiology, etiology, pathophysiology, evaluation, and current management. We also set to provide further insight on the treatment of this condition from the experience derived from patients cared for at our tertiary-care institution. NE affects approximately 15% of all children at 5-year-old, affecting boys more frequently than girls. At our large university tertiary pediatric urology center, NE and incontinence, in general, is one the most common chief complaints prompting urologic care. In this review, we examine the condition in detail, highlighting specific goals of the initial evaluation and treatment. We contrast the commonly implemented treatment recommendations, available from the literature with strategies we have found valuable from our extensive experience in treating patients with this disorder. Using current urologic reference textbooks, book chapters, Medline, journal articles and reviews describing the many aspects of NE were reviewed in order to describe NE and the current practices at our institution. Although, this is not a systematic literature review, it includes relevant available research, institutional experience and urological expert opinion and current practices at a tertiary state health facility. The treatment of NE remains a challenge for many pediatricians and pediatric urologists. This likely stems from the multiple possible etiologies of the disorder. We have established a treatment algorithm at our institution, which we have found successful in the majority of our patients. This consists of starting patients on urotherapy, then offering both the enuresis alarm device and medication therapy as first line treatments, and finally adding anticholingerics for combination therapy. Our hope is with further research the treatment of NE will continue to improve.


DsRNA degradation in the pea aphid (Acyrthosiphon pisum) associated with lack of response in RNAi feeding and injection assay.
Over the past decade, RNA interference (RNAi), the sequence-specific suppression of gene expression, has proven very promising for molecular research in many species, including model insects as Tribolium castaneum and Apis mellifera. It showed its usefulness to analyze gene function and its potential to manage pest populations and reduce disease pathogens. However, in several insects, the efficiency of RNAi is low or very variable at best. One of the factors that could influence RNAi efficiency in insects is degradation of dsRNA after administration to the insect. In this paper, we report on the importance of dsRNA breakdown in the pea aphid (Acyrthosiphon pisum) associated with the absence of an RNAi response upon oral feeding and injection with dsRNA targeting different genes such as the ecdysone hormone receptor and ultraspiracle. In essence, we discovered that both the salivary secretions of aphids and the hemolymph were able to degrade the dsRNA. In parallel, introduction of dsRNA in the aphid body was not able to provoke a response in the expression of the siRNA core machinery genes.


Lattice Boltzmann solution of the transient Boltzmann transport equation in radiative and neutron transport.
Applications of the transient Boltzmann transport equation (BTE) have undergone much investigation, such as radiative heat transfer and neutron transport. This paper provides a lattice Boltzmann model to efficiently resolve the multidimensional transient BTE. For a higher angular resolution, enough transport directions are considered while the transient BTE in each direction is treated as a conservation law equation and solved independently. Both macroscopic equations recovered from a Chapman-Enskog expansion and simulated results of typical benchmark problems show not only the second-order accuracy but also the flexibility and applicability of the proposed lattice Boltzmann model. This approach may contribute a powerful technique for the parallel simulation of large-scale engineering and some alternative perspectives for solving the nonlinear transport problem further.


Experimental validation of in silico estimated biomass yields of Pseudomonas putida KT2440.
Pseudomonas putida is rapidly becoming a microbial cell platform for biotechnological applications. In order to understand genotype-phenotype relationships genome scale models represent helpful tools. However, the validation of in silico predictions of genome scale models is a task that is rarely performed. In this study the theoretical biomass yields of Pseudomonas putida KT2440 were estimated for 57 different carbon sources based on a genome scale stoichiometric model applying flux balance analysis. The batch growth of P. putida KT2440 with six individual carbon sources covering the range of maximal to minimal in silico biomass yields (acetate, glycerol, citrate, succinate, malate and methanol, respectively) was studied in a defined mineral medium in a fully controlled stirred-tank bioreactor on a 3 L scale. The highest growth rate of P. putida KT2440 was measured with succinate as carbon source (0.51 h-1 ). Among the 57 carbon sources tested, glycerol resulted in the highest estimated biomass yield (0.61 molCBiomass molC-1Glycerol ) which was experimentally confirmed. The comparison of experimental determined biomass yields with a modified version of the model iJP815 showed deviations of only up to 10%. The experimental data generated in this study can also be used in future studies to further improve the genome scale models of P. putida KT2440. Improved models will then help to gain deeper insights in genotype-phenotype relationships.


Pulmonary Function in Human Spaceflight.
Human spaceflight is entering a time of markedly increased activity fueled by collaboration between governmental and private industry entities. This has resulted in successful mission planning for destinations in low Earth orbit, lunar destinations (Artemis program, Gateway station) as well as exploration to Mars. The planned construction of additional commercial space stations will ensure continued low Earth orbit presence and destinations for science but also commercial spaceflight participants. The human in the journey to space is exposed to numerous environmental challenges including increased gravitational forces, microgravity, altered human physiology during adaptation to weightlessness in space, altered ambient pressure, as well as other important stressors contingent on the type of mission and destination. This chapter will cover clinically important aspects relevant to lung function in a normally proceeding mission; emergency scenarios such as decompression, fire, etc., will not be covered as these are beyond the scope of this review. To date, participation in commercial spaceflight by those with pre-existing chronic medical conditions is very limited, and hence, close collaboration between practicing pulmonary specialists and aerospace medicine specialists is of critical importance to guarantee safety, proper clinical management, and hence success in these important endeavors.


Myocarditis in sibling boxer puppies associated with Citrobacter koseri infection.
Two sibling Boxer puppies presented with severe suppurative myocarditis in the absence of additional disseminated suppurative foci. The identification of gram-negative bacteria within areas of myocarditis in both puppies and the pure growth of large numbers of Citrobacter koseri from the myocardial lesions in one of the dogs were consistent with a bacterial etiology. The fact that C. koseri is an opportunist pathogen suggested intercurrent immunosuppression. The finding of a concomitant bacterial myocarditis in two canine siblings is novel. The case is also unusual in that syncope could be related to the myocardial injury.


Modification of buccal drug delivery following pretreatment with skin penetration enhancers.
The effect of the lipophilic skin penetration enhancers octisalate (OS), padimate O (PO), and Azone (AZ) on in vitro buccal permeability was assessed using caffeine (CAF), estradiol (E2), and triamcinolone acetonide (TAC) as model permeants. Buccal permeability was assessed in modified Ussing chambers, through both untreated porcine buccal mucosa and mucosa pretreated with an enhancer (5% w/v in 95% v/v ethanol) or ethanol alone. To ensure sink conditions were present, E2 permeability experiments were also performed with bovine serum albumin (BSA) 4% in the receptor solution. Mucosa-buffer partition studies were performed to determine the effect of enhancer pretreatment on the log mucosa-buffer partition coefficient (logK) of E2 and TAC. CAF permeability was only increased following pretreatment with ethanol 95%. E2 buccal transport was not altered following OS pretreatment, but was reduced by 26.3% with PO pretreatment and 67.6% with AZ pretreatment. Similar results were obtained with BSA 4% in the receptor solution. The logK of E2 was increased 1.4-fold and 2.2-fold in PO- and AZ-pretreated tissues, respectively, suggesting that the reduction in flux caused by PO and AZ may have been due to enhanced E2 tissue retention. The effect of OS and PO on TAC permeability was no different to that of ethanol. However, AZ enhanced TAC permeability 4.1-fold and this was accompanied by a 2.4-fold increase in the logK of TAC.


Evaluation of suture material characteristics in an in vitro experimental model.
The purpose of our study was to indentify the mechanical characteristics of various suture materials. We created an in-vitro experimental flexor tendon model. Materials were divided into four groups: monofilament polypropylene non-absorbable material (group 1); monofilament long-term absorbable material (group 2); polyester multifilament non-absorbable coated material (group 3) and polyester multifilament non-absorbable uncoated material (group 4). We performed 135 tests. The mean maximal tensile strength was 62.92 N in group 1, 75.20 N in group 2, 36.38 N in group 3 and 72.4 N in group 4. Elasticity in millimetres was adjusted at the 35N level: group 1:2.01 mm, group 2:2.18 mm, group 3:2.14 and group 4:1.51 mm. With regard to its elasticity and favourable SD for tensile strength measurements, polyester multifilament non-absorbable uncoated material was considered to be the most suitable material.


Somatization Disorder in Elderly Patients.
Little is known about the prevalence, characteristics, or natural history of somatization disorder in elderly patients. The authors evaluated 353 adult women (from outpatient psychiatric and medical clinics) for somatization disorder. Twenty-four percent of patients were 55 years old or older. The sample of older women did not differ from younger women in the proportion who were positive for somatization disorder, the number of somatic symptoms, or characteristics of the disorder. The authors compare these findings with prior literature and make suggestions for future prospectively designed studies.


Phase II study of etoposide, ifosfamide, and mitoxantrone for the treatment of resistant adult acute lymphoblastic leukemia.
Although combination chemotherapy induces complete remission in 60-90% of adults with acute lymphoblastic leukemia, only 20-45% of patients remain in continued remission 5 years from diagnosis. For patients with a short first remission, multiple relapses, or patients with disease refractory to initial induction chemotherapy, few salvage treatments are successful. To improve the results of salvage therapy we studied the efficacy and toxicity of a combination of etoposide (100 mg/m2 IV qd x 5), ifosfamide (1.5 g/m2/d x 5), and mitoxantrone (8 mg/m2/d IV x 3) in 11 adult patients with relapsed or refractory ALL. The median follow-up of all patients completing therapy is 208 days (30-484+ days). Eight of 11 (73%; 95% confidence interval 45-92%) achieved a complete remission, two patients failed to enter remission, and one patient died of multiorgan system failure shortly after receiving therapy. Median DFS is 96 days and median survival from remission is 234 days. Five patients who achieved CR subsequently relapsed with a median time to relapse of 80 days (50-151 days). Median time to granulocyte > .5 x 10(9)/L was 28 days (21-46 days) and the median time to platelet recovery > 20 x 10(9)/L was 24 days (21-39 days). Although gastrointestinal toxicity was common, no patient developed severe cardiac, hepatic, pulmonary, or neurologic complications. These results demonstrate that the combination of etoposide, ifosfamide, and mitoxantrone can be used as an effective salvage therapy for patients with resistant ALL.


The sulfur-bubble template-mediated synthesis of uniform porous g-C3N4 with superior photocatalytic performance.
A facile sulfur-bubble template-mediated synthesis of uniform porous g-C3N4 has been developed for the first time. The obtained sulfur-mediated g-C3N4 presents a uniform porous structure with higher BET surface area and displays superior photocatalytic performance compared with pure g-C3N4.


Vitamin D and respiratory health in the Busselton Healthy Ageing Study.
The relationship between vitamin D and respiratory disease was examined by cross-sectional analysis of a large community-based sample. Serum 25-hydroxyvitamin D (25OHD) and history of respiratory disease, symptoms (recorded by questionnaire) and spirometry were measured in 5011 adults aged 45-69 years. Adjustments were made for age, sex, season and smoking (Model A), plus body mass index (BMI) and physical activity level (Model B), plus history of chronic diseases (Model C). Mean (SD) age was 58 (SD 6) years with 45% males, 10% current smokers and 12% taking vitamin D supplements. The prevalence of 25OHD level <50 nmol/L was 8.0%. In all the three models, 25OHD <50 nmol/L was significantly associated with asthma (Model C: odds ratio (OR): 1.32; 95% CI: 1.00, 1.73), bronchitis (1.54; 1.17, 2.01), wheeze (1.37; 1.10, 1.71) and chest tightness (1.42; 1.10, 1.83). Participants with vitamin D level > 100 nmol/L had higher forced vital capacity (FVC) in all the three models (1.17% higher, compared with the 50-100 nmol/L group in Model C). Low levels of serum 25OHD were independently associated with asthma, bronchitis, wheeze and chest tightness after three levels of adjustment for potential confounders. Higher vitamin D levels were associated with higher levels of lung function.


Peripheral T-cell lymphoma presenting as sclerouveitis.
To report an unusual case of ocular peripheral T-cell lymphoma presenting as sclerouveitis. A 53-year-old woman presented with painful, unilateral sclerouveitis and was initially treated with antivirals and corticosteroids for what was presumed to be isolated ocular HSV infection with vasculitis. When she failed to improve the conjunctiva was biopsied and characterized by immunohistochemical and molecular methods. The literature regarding conjunctival T-cell lymphomas as well as lymphomas mimicking scleritis is reviewed. Biopsies of a scleral/conjunctival nodule from the right eye were obtained on 2 occasions, the second of which revealed the presence of intermediate to large size lymphocytes that were CD3, T-cell intracellular antigen 1 and Granzyme B positive but CD56 and Epstein Barr virus negative. Polymerase chain reaction showed clonal T-cell receptor gamma rearrangements in DNA samples isolated from biopsy tissue. Another biopsy was obtained from a mucosal lesion in the oropharynx, which was shown to contain an identical T-cell receptor gamma rearrangement. These results led to the diagnosis of peripheral T-cell lymphoma. Conjunctival T-cell lymphomas have been reported in two other patients both of which also had involvement of upper airway structures. Five other reports of lymphoma mimicking scleritis are discussed. Peripheral T-cell lymphoma should be considered in the differential diagnosis of patients who present with sclerouveitis of unknown etiology unresponsive to conventional therapy. If a conjunctival T-cell lymphoma is identified a systemic evaluation for lymphoma with particular attention to the upper airway is justified.


Growth of attached actin filaments.
In several studies of actin-based cellular motility, the barbed ends of actin filaments have been observed to be attached to moving obstacles. Filament growth in the presence of such filament-obstacle interactions is studied via Brownian dynamics simulations of a three-dimensional energy-based model. We find that with a binding energy greater than 24k B T and a highly directional force field, a single actin filament is able to push a small obstacle for over a second at a speed of half of the free filament elongation rate. These results are consistent with experimental observations of plastic beads in cell extracts. Calculations of an external force acting on a single-filament-pushed obstacle show that for typical in vitro free-actin concentrations, a 3pN pulling force maximizes the obstacle speed, while a 4pN pushing force almost stops the obstacle. Extension of the model to treat beads propelled by many filaments suggests that most of the propulsive force could be generated by attached filaments.