Ophthalmic findings in patients with arterial tortuosity syndrome and carriers: A case series.
Arterial tortuosity syndrome (ATS) is a rare autosomal recessive disease hallmarked by tortuosity, stenosis, and aneurysm development of large- and medium-sized arteries. Mutations in SLC2A10, a gene that encodes the facilitative glucose transporter GLUT10, cause ATS. Several case reports have noted associated ophthalmic findings such as keratoconus, keratoglobus, and myopia without detailed descriptions or standardized examinations. We report the ophthalmic findings in a cohort of compound heterozygous ATS patients and heterozygous carriers of SLC2A10 mutations. Five ATS patients and three carriers were identified through an ATS specialty clinic at the Arkansas Children's Hospital in Little Rock, Arkansas. Patients underwent complete eye examinations, including corneal pachymetry, topography, and optical coherence tomography when indicated. All five patients with ATS had myopia and thin corneas with an average central corneal thickness of 426 µm, and three had corneal ectasia, two with early keratoconus and one with keratoglobus and deep stromal corneal opacities. One patient had bilateral high irregular astigmatism, and one had unilateral high regular astigmatism. All carriers had myopia, one had corneal thinning, and one developed keratectasia in one eye many years after laser-assisted in situ keratomileusis (LASIK) surgery. We document a spectrum of ophthalmic manifestations of ATS with universal findings of myopia, corneal thinning, and a propensity for corneal ectasia leading to keratoconus or keratoglobus. Heterozygous carriers may develop keratectasia after corneal refractive surgery. Our data support regular eye examinations for all patients carrying SLC2A10 mutations with follow-up tailored to clinical findings.


Separation, identification and rapid determination of liensine, isoliensinine and neferine from embryo of the seed of Nelumbo nucifera Gaertn. by liquid chromatography coupled to diode array detector and tandem mass spectrometry.
An application of mass spectrometric methods has been developed to characterize, prepare and quantitatively analyze three bisbenzylisoquinoline alkaloids (liensinine, isoliensinine and neferine) from embryo of the seed of Nelumbo nucifera Gaertn. Initially, an analytical method based on liquid chromatography electrospray ionization tandem mass spectrometry (LC-ESI-MS/MS) with positive ionization mode using a MonoChrom C18 column (4.6 mm x 250 mm i.d. 10 microm) has been developed to characterize liensinine, isoliensinine and neferine, and then scaled up to purify them on a 21.4 mm x 250 mm preparative column. The structures of liensinine, isoliensinine and neferine were elucidated by NMR. Finally, a LC-MS/MS determination method, successfully applied to separation within 3 min, was developed for high throughput simultaneous measurement of liensinine, isoliensinine, and neferine in the extract samples. Multiple reaction monitoring (MRM) was used to monitor the transition of the protonated molecules m/z 611, 611, 625 [M+H]+ to the product ions m/z 206, 192, 206 for analysis of liensinine, isoliensinine and neferine. The LC-MS/MS system was linear in the concentration range of 0.0247-6.02 microg/ml with correlation coefficients of r2>0.992. The quantitative method was validated, with an S/N=3 detection limit of 0.15 ng for liensinine, 0.19 ng for isoliensinine and 0.1 2ng for neferine. The mass fractions of liensinine, isoliensinine, and neferine in the crude extract and the phenolic alkaloid sample of embryo of the seed of N. nucifera Gaertn. were 16.5+/-1.1 and 228.6+/-11.9 for liensinine (mg/g), 45.7+/-1.8 and 640.7+/-15.2 for isoliensinine (mg/g), 59.7+/-6.4 and 58.8+/-9.8 for neferine (mg/g).


Genomic origin and EGFR-TKI treatments of pulmonary adenosquamous carcinoma.
Adenosquamous carcinoma (ASC) of the lung is a heterogeneous disease that is composed of both adenocarcinoma components (ACC) and squamous cell carcinoma components (SCCC). Their genomic profile, genetic origin, and clinical management remain controversial. Resected ASC and metastatic tumor in regional lymph nodes (LNs) were collected. The ACC and SCCC were separated by microdissection of primary tumor. The 1021 cancer-related genes were evaluated by next-generation sequencing independently in ACC and SCCC and LNs. Shared and private alterations in the two components were investigated. In addition, genomic profiles of independent cohorts of adenocarcinomas and squamous cell carcinomas were examined for comparison. We have also carried out a retrospective study of ASCs with known EGFR mutation status from 11 hospitals in China for their clinical outcomes. The most frequent alterations in 28 surgically resected ASCs include EGFR (79%), TP53 (68%), MAP3K1 (14%) mutations, EGFR amplifications (32%), and MDM2 amplifications (18%). Twenty-seven patients (96%) had shared variations between ACC and SCCC, and pure SCCC metastases were not found in metastatic LNs among these patients. Only one patient with geographically separated ACC and SCCC had no shared mutations. Inter-component heterogeneity was a common genetic event of ACC and SCCC. The genomic profile of ASC was similar to that of 170 adenocarcinomas, but different from that of 62 squamous cell carcinomas. The incidence of EGFR mutations in the retrospective analysis of 517 ASCs was 51.8%. Among the 129 EGFR-positive patients who received EGFR-TKIs, the objective response rate was 56.6% and the median progression-free survival was 10.1 months (95% confidence interval: 9.0-11.2). The ACC and SCCC share a monoclonal origin, a majority with genetically inter-component heterogeneity. ASC may represent a subtype of adenocarcinoma with EGFR mutation being the most common genomic anomaly and sharing similar efficacy to EGFR TKI.


Cardiac patching and the regeneration of infarcted myocardium: where do we go from here?
Serpooshan V, Zhao M, Metzler SA et al. The effect of bioengineered acellular collagen patch on cardiac remodeling and ventricular function postmyocardial infarction. Biomaterials 34, 9048-9055 (2013). The decline of cardiac function in the post-myocardial infarcted (MI) heart is due to two essential problems: massive loss of contractile cardiomyocytes, and loss of structural and mechanical tissue integrity due to ongoing remodeling of scar tissue, often leading to left ventricular dilation. Serpooshan et al. demonstrate that an engineered acellular type I collagen patch with optimized mechanical properties, grafted onto the epicardium of infarcted adult murine hearts following ligation of the left anterior descending artery, significantly improves cardiac function and reduces left ventricular remodeling 4 weeks postinjury. While these short-term results are encouraging and, like in other studies, prove the relevance of mechanically supporting the injured myocardium, optimization of the approach in terms of time and manner of intervention, as well as origin of the biomaterial, is needed to warrant future clinical application.


Extending otology services to rural settings: Value of endoscopic ear surgery.
Few centers, mainly located in urban settings offer otological surgical services, yet majority of patients requiring these services are rural based and are generally unable to access these centers with resulting disease chronicity and complications. This paper aims to describe the access of otological surgical services by a rural population. This is a retrospective study of patients who accessed otological services at three secondary health institutions and one tertiary referral institution. All patients requiring ear surgery over a 4-year period were studied. The initial 2 years without ear endoscopic surgery was compared with the 2 years when ear endoscopic surgery was introduced. Hospital records were studied and relevant data were extracted. Six hundred and nine ears required surgery over 4 years. Age ranged from 3 to 62 years, with a ratio of 1.4 males: 1 female. During the initial 2 years, all patients were referred from the three secondary health institutions to the urban-based tertiary institution for microscopic ear surgery, 94% failed to proceed on the referral. In the second 2 years, 34% were considered suitable for endoscopic ear surgery, of which 78% accepted and had surgery within the locality. Of the 66% referred, only 5% proceeded on the referral. With operator training and investment in portable ear endoscopy set, bulk of ear surgery needing magnification can be treated in the rural setting. This represents a most feasible means of extending the service to the targeted population.


Expression of interleukin-10 in advanced human atherosclerotic plaques: relation to inducible nitric oxide synthase expression and cell death.
Inflammation is a major feature of human atherosclerosis and is central to development and progression of the disease. A variety of proinflammatory cytokines are expressed in the atherosclerotic plaque and may modulate extracellular matrix remodeling, cell proliferation, and cell death. Little is known, however, about the expression and potential role of anti-inflammatory cytokines in human atherosclerosis. Interleukin-10 (IL-10) is a major anti-inflammatory cytokine whose expression and potential effects in advanced human atherosclerotic plaques have not been evaluated. We studied 21 advanced human atherosclerotic plaques. IL-10 expression was analyzed by use of reverse transcription-polymerase chain reaction and immunohistochemical techniques. Inducible nitric oxide synthase expression was assessed by using immunohistochemistry, and cell death was determined by use of the TUNEL method. Reverse transcription-polymerase chain reaction identified IL-10 mRNA in 12 of 17 atherosclerotic plaques. Immunohistochemical staining of serial sections and double staining identified immunoreactive IL-10 mainly in macrophages, as well as in smooth muscle cells. Consistent with its anti-inflammatory properties, high levels of IL-10 expression were associated with significant decrease in inducible nitric oxide synthase expression (P<0.0001) and cell death (P<0. 0001). Hence, IL-10, a potent anti-inflammatory cytokine, is expressed in a substantial number of advanced human atherosclerotic plaques and might contribute to the modulation of the local inflammatory response and protect from excessive cell death in the plaque.


Adrenal incidentaloma: a case of carcinoma.
Adrenal incidentaloma (AI) is a term applied to an accidentally discovered adrenal mass on imaging performed for reasons unrelated to adrenal pathology. The widespread application of abdominal imaging procedure has resulted in an increased frequency of clinically silent adrenal masses. Although most AIs are nonfunctioning benign adenomas, a multidisciplinary approach with biochemical and radiological evaluation is needed to characterize these lesions and identify patients who are at high risk for hormonal or malignant evolution. Herein, we describe a case of a 69-year-old man with a pain at the base of right chest. On the basis of clinical evaluation, biochemical analysis, as well as imaging procedures, a diagnosis of right adrenocortical carcinoma was made. The patient underwent medical treatment.


Injectable treatments for the aging face.
The use of injectable agents, specifically soft tissue fillers and botulinum toxin type A, has risen dramatically over recent years, due to the increased demand for minimally invasive techniques. In fact, today they represent the most commonly performed cosmetic procedures in the United States, with botulinum type A injections topping the list. In the treatment of the aging face, these agents, when used individually or in combination, can effectively decrease rhytids and restore lost volume. The result is a fuller, smoother, more youthful appearance. This article provides an overview of botulinum type A (Botox Cosmetic; Allergan, Inc., Irvine, CA) and the two injectable fillers most commonly used in our practice, namely hyaluronic acid (Restalyne; Medicis Aesthetics, Inc., Scottsdale, AZ) and human-derived collagen (Cosmoderm and Cosmoplast; Inamed Aesthetics, Inc., Santa Barbara, CA). Although we commonly use autologous fat as an injectable filler for facial-volume augmentation, its discussion is beyond the scope of this article. Conceptually, the aging face can be divided into upper, middle, and lower thirds. Using this framework, we will discuss our treatment strategies for addressing each facial region. General principles, preinjection evaluation, and specific approaches and techniques for each anatomic region will be discussed, with particular emphasis on the benefit of using dermal fillers in conjunction with botulinum toxin type A to achieve optimal aesthetic results for facial rejuvenation.


Use of proton pump inhibitors during pregnancy and breastfeeding.
A 36-year-old pregnant patient has symptoms of peptic disease. Treatment with diet and lifestyle modifications and also antacids has given her little relief. If she were not pregnant, I would prescribe a proton pump inhibitor (PPI) for her. She is now 4 weeks pregnant, and I need to determine whether PPIs are safe during pregnancy. Data currently available suggest that omeprazole is not teratogenic in humans. While information on other PPIs is limited, a systematic review of the evidence suggests that they are also not teratogenic.


[Definitive or exploratory periodontal experimentation: an overview of the literature].
Definitive and exploratory randomized controlled trials (RCTs) have different goals as well as different design and analysis characteristics. The goal of definitive studies is to provide unequivocal evidence of a treatment's tangible benefit to the patient; a pre-trial-specified hypothesis is tested by use of a pre-trial-specified method. The goal of exploratory studies is to elucidate biological treatment mechanisms, to identify promising treatments, and to generate hypotheses for definitive studies: multiple hypotheses are evaluated to extract as much information from the data as possible. The purposes of this study were: (1) to survey selected design and analysis characteristics of randomized controlled periodontal trials published between 1988 and 1992 (n = 86), and (2) to classify trials as exploratory or definitive studies. The periodontal RCTs surveyed were typical of exploratory studies whose primary goal was to elucidate biological treatment mechanisms. Trial reports indicated the testing of multiple hypotheses (> or = 6 hypothesis tests in 70 of the 86 trials) on a variety of biological markers (86 out of 86 trials). The sample size (< or = 30 subjects in 67 out of 86 trials), duration (< or = 6 months in 65 out of 86 trials), and design and analysis characteristics (e.g., an absence of masking in 57 out of 86 trials) were also typical of exploratory studies which strive to obtain quick answers (short duration) at a low cost (small sample size; accept bias for increased efficiency and a lower cost). No definitive trials were identified. Promising, biologically active, treatments identified in exploratory trials should be evaluated in definitive studies where the primary goal is the procurement of unequivocal evidence of a treatment's tangible benefit to the patient. The costs and benefits of conducting definitive periodontal RCTs to provide such evidence should be investigated.


[Brazilian Nursing Magazine--a history of resistance].
Part of the conquest of ANEDB, since 1920 the REBEn itself inserting in the professional dispute about the diffusion of the nursing facts. Ought to Edith Magalhães Fraenkel and Rachel Haddock Lobo the inspiration and initiative for the creation, since 1929, within the participation in the I Quadrienal of ICN congress, in Montreal where were discussed facilities, difficulties and advance of nursing newspaper. The ANNAES of nursing, edited by the newspaper "Journal do Brasil--R.J.", in 1932, was the precursor of the REBEn. With her existence, readers, students and Professionals greediness for extend his specifics knowledge, constructors of the historic documentation and the knowledge profession, responsible by the scientific and technologic development and by the concept emission of different period of the Brazilian nursing, has learned to take advantage on his benefits. With more of 50 volumes and 200 edited copies the REBEn has acquired a reference status in the domestic and international of health and human science areas. Already consolidate; spread dissertation results, thesis, and work papers, presented or showed in Brazilian congresses of nursing. It's the most consulted newspaper as source and field scientific investigation. It provides the readers growth, organizer in the editorial process and counselors formation "ad hoc" through the permanent criticism and evaluation.


IoT in Healthcare: Achieving Interoperability of High-Quality Data Acquired by IoT Medical Devices.
It is an undeniable fact that Internet of Things (IoT) technologies have become a milestone advancement in the digital healthcare domain, since the number of IoT medical devices is grown exponentially, and it is now anticipated that by 2020 there will be over 161 million of them connected worldwide. Therefore, in an era of continuous growth, IoT healthcare faces various challenges, such as the collection, the quality estimation, as well as the interpretation and the harmonization of the data that derive from the existing huge amounts of heterogeneous IoT medical devices. Even though various approaches have been developed so far for solving each one of these challenges, none of these proposes a holistic approach for successfully achieving data interoperability between high-quality data that derive from heterogeneous devices. For that reason, in this manuscript a mechanism is produced for effectively addressing the intersection of these challenges. Through this mechanism, initially, the collection of the different devices' datasets occurs, followed by the cleaning of them. In sequel, the produced cleaning results are used in order to capture the levels of the overall data quality of each dataset, in combination with the measurements of the availability of each device that produced each dataset, and the reliability of it. Consequently, only the high-quality data is kept and translated into a common format, being able to be used for further utilization. The proposed mechanism is evaluated through a specific scenario, producing reliable results, achieving data interoperability of 100% accuracy, and data quality of more than 90% accuracy.


Association between skeletal muscle mass and cardiorespiratory fitness in community-dwelling elderly men.
Sarcopenia reduces physical ability and cardiorespiratory fitness (CRF), leading to poor quality of life. The aim of this study was to investigate the relationship between skeletal muscle mass and CRF in elderly men. We assessed 102 community-dwelling men over 60 years old. Appendicular skeletal muscle mass (ASM) was determined using bioelectrical impedance analysis, and the skeletal muscle mass index (SMI) was calculated as ASM divided by the square of height. Subjects with an SMI less than 7.0 kg/m2 were included in the sarcopenic group, as recommended by the Asian Working Group for Sarcopenia. To investigate CRF parameters, a cardiopulmonary exercise test was performed using the Bruce protocol. CRF parameters were subdivided into aerobic capacity, cardiovascular response, and ventilatory response. Of the 102 subjects, 15 (14.7%) were included in the sarcopenic group. There were significant correlations between SMI and peak oxygen consumption (VO2peak) (r = 0.597, p < 0.001), and between SMI and VO2peak/weight (r = 0.268, p = 0.024). Moreover, there were positive correlations between SMI and first ventilatory threshold (VT1) (r = 0.352, p = 0.008) and between SMI and VT1/weight (r = 0.189, p = 0.039). Additionally, peak oxygen pulse (O2pulsepeak) was significantly correlated with SMI (r = 0.558, p < 0.001). VO2peak, VO2peak/weight and O2pulsepeak showed significant differences between the sarcopenic and non-sarcopenic groups (p < 0.05, all). In multiple linear regression analyses, the factor related to VO2peak was SMI (β = 0.473, p < 0.001) and that related to O2pulsepeak was also SMI (β = 0.442, p < 0.001). This study demonstrated that skeletal muscle mass might be closely associated with CRF. Therefore, sarcopenia should be appropriately managed to improve an individual's CRF.


Differentiation potential of stem cells from human dental origin - promise for tissue engineering.
Recent studies have revealed the existence of stem cells in various human tissues including dental structures. We aimed to establish primary cell cultures from human dental pulp and periodontal ligament, to identify multipotential adult stem cells in these cultures, and to study the differentiation capacity of these cells to osteogenic and to neuronal fates. Dental pulp and the periodontal ligament were isolated from extracted human wisdom teeth. The extracellular matrix was enzymatically degraded to obtain isolated cells for culturing. Both dental pulp and periodontal ligament derived cultures showed high proliferative capacity and contained a cell population expressing the STRO-1 mesenchymal stem cell marker. Osteogenic induction by pharmacological stimulation resulted in mineralized differentiation as shown by Alizarin red staining in both cultures. When already described standard neurodifferentiation protocols were used, cultures exhibited only transient neurodifferentiation followed by either redifferentiation into a fibroblast-like phenotype or massive cell death. Our new three-step neurodifferentiation protocol consisting of (1) epigenetic reprogramming, then (2) simultaneous PKC/PKA activation, followed by (3) incubation in a neurotrophic medium resulted in robust neurodifferentiation in both pulp and periodontal ligament cultures shown by cell morphology, immunocytochemistry and real time PCR for vimentin and neuron-specific enolase. In conclusion, we report the isolation, culture and characterization of stem cell containing cultures from both human dental pulp and periodontal ligament. Furthermore, our data clearly show that both cultures differentiate into mineralized cells or to a neuronal fate in response to appropriate pharmacological stimuli. Therefore, these cells have high potential to serve as resources for tissue engineering not only for dental or bone reconstruction, but also for neuroregenerative treatments.


Analysis of patient data from laboratories during the Ebola virus disease outbreak in Liberia, April 2014 to March 2015.
An outbreak of Ebola virus disease (EVD) in Liberia began in March 2014 and ended in January 2016. Epidemiological information on the EVD cases was collected and managed nationally; however, collection and management of the data were challenging at the time because surveillance and reporting systems malfunctioned during the outbreak. EVD diagnostic laboratories, however, were able to register basic demographic and clinical information of patients more systematically. Here we present data on 16,370 laboratory samples that were tested between April 4, 2014 and March 29, 2015. A total of 10,536 traceable individuals were identified, of whom 3,897 were confirmed cases (positive for Ebola virus RNA). There were significant differences in sex, age, and place of residence between confirmed and suspected cases that tested negative for Ebola virus RNA. Age (young children and the elderly) and place of residence (rural areas) were the risk factors for death due to the disease. The case fatality rate of confirmed cases decreased from 80% to 63% during the study period. These findings may help support future investigations and lead to a fuller understanding of the outbreak in Liberia.


Cloning and deletion analysis of a genomic segment of Bacillus subtilis coding for the sdhA, B, C (succinate dehydrogenase) and gerE (spore germination) loci.
From a Bacillus subtilis gene bank constructed in Escherichia coli and based on a low copy number cloning vector we have isolated a hybrid plasmid, pSH1047, containing an 8.0 kb segment of B. subtilis DNA coding for the sdhA, B and C genes, which code for the component polypeptides of succinate dehydrogenase, and the gerE gene, which may code for or regulate a protease involved in producing spores which germinate normally. We report the restriction map of this segment and the analysis of deletion derivatives which allow us to correlate the physical and genetic maps of these chromosomal segments.


"Hidden" cytotoxic antibodies that react with allogeneic cultured fetal and tumor cells contained in soluble immune complexes from normal human sera.
Hidden complement-dependent cytotoxins were demonstrated in normal donor sera after removing anti-immunoglobulins that normally block the ability of these immunoglobulin Gs to react with surface antigens on tumor cells. The blocking antibodies had certain properties of anti-idiotypes. Immunoglobulin G from Cohn Fraction II, after removing these anti-immunoglobulins, was cytotoxic for cultured fetal cells and for malignant melanoma, breast, lung, colon, and other tumor cells maintained either in tissue culture or by serial passage in nude mice. The cytotoxins were not adsorbed by extracts from normal lymphoid, liver, skin, or red blood cells. These results suggest that a heterogeneous group of natural antibodies reactive with antigens expressed on a variety of neoplastic and fetal cells circulate in normal donor sera as part of a soluble immune complex, together with a blocking anti-immunoglobulin.


Thyroid-stimulating hormone suppression therapy for differentiated thyroid cancer: The role for a combined T3/T4 approach.
In the management of differentiated thyroid carcinoma, surgery with or without postoperative radioiodine, and thyroid-stimulating hormone (TSH) suppression is the standard of care in most patients. Levothyroxine is recommended for long-term TSH suppression. For some patients, this may be difficult to tolerate due to adverse effects, such as impaired cognitive function. This article reviews the evidence for the role of combination treatment with triiodothyronine (T3) and levothyroxine (T4) in these patients. The evidence for combination T3 and T4 treatment comes mainly from studies on hypothyroidism, and research into its use for TSH suppression is limited. Although the evidence base is not strong, there is a small group of patients who may benefit from combination T3 and T4 treatment due to difficulty tolerating thyroxine. Until further evidence is available, a case-by-case approach is recommended.


Factors Delaying the Continuum of Care for the Management of Traumatic Brain Injury in Low- and Middle-Income Countries: A Systematic Review.
Considering the disproportionate burden of delayed traumatic brain injury (TBI) management in low- and middle-income countries (LMICs), there is pressing demand for investigations. Therefore, our study aims to evaluate factors delaying the continuum of care for the management of TBIs in LMICs. A systematic review was conducted with PubMed, Scopus, Google Scholar and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Observational studies with TBI patients in LMIC were included. The factors affecting management of TBI were extracted and analyzed descriptively. A total of 55 articles were included consisting of 60,603 TBI cases from 18 LMICs. Road traffic accidents (58.7%) were the most common cause of injury. Among included studies, factors contributing to prehospital delays included a poor referral system and lack of an organized system of referral (14%), long travel distances (11%), inadequacy of emergency medical services (16.6%), and self-treatment practices (2.38%). For in-hospital delays, factors such as lack of trained physicians (10%), improper triage systems (20%), and absence of imaging protocols (10%), lack of in-house computed tomography scanners (35%), malfunctioning computed tomography scanners (10%), and a lack of invasive monitoring of intracranial pressure (5%), limited theater space (28%), lack of in-house neurosurgical facilities (28%), absence of in-house neurosurgeons (28%), and financial constraints (14%) were identified. Several factors, both before and during hospitalization contribute to delays in the management of TBIs in LMICs. Strategically addressing these factors can help overcome delays and improve TBI management in LMICs.


[Results of the treatment of incarcerated abdominal hernias].
The experience with treatment of 129 patients with incarcerated abdominal hernia is presented. Postoperative lethality was 1.6%. Hernia recurrency was revealed in 4.9% of the patients.


Low-density lipoprotein promotes microvascular thrombosis by enhancing von Willebrand factor self-association.
von Willebrand factor (VWF) mediates primary hemostasis and thrombosis in response to hydrodynamic forces. We previously showed that high shear promoted self-association of VWF into hyperadhesive strands, which can be attenuated by high-density lipoprotein (HDL) and apolipoprotein A-I. In this study, we show that low-density lipoprotein (LDL) binds VWF under shear and enhances self-association. Vortexing VWF in tubes resulted in its loss from the solution and deposition onto tube surfaces, which was prevented by HDL. At a stabilizing HDL concentration of 1.2 mg/mL, increasing concentrations of LDL progressively increased VWF loss, the effect correlating with the LDL-to-HDL ratio and not the absolute concentration of the lipoproteins. Similarly, HDL diminished deposition of VWF in a post-in-channel microfluidic device, whereas LDL increased both the rate and extent of strand deposition, with both purified VWF and plasma. Hypercholesterolemic human plasma also displayed accelerated VWF accumulation in the microfluidic device. The initial rate of accumulation correlated linearly with the LDL-to-HDL ratio. In Adamts13-/- and Adamts13-/-LDLR-/- mice, high LDL levels enhanced VWF and platelet adhesion to the myocardial microvasculature, reducing cardiac perfusion, impairing systolic function, and producing early signs of cardiomyopathy. In wild-type mice, high plasma LDL concentrations also increased the size and persistence of VWF-platelet thrombi in ionophore-treated mesenteric microvessels, exceeding the accumulation seen in similarly treated ADAMTS13-deficient mice that did not receive LDL infusion. We propose that targeting the interaction of VWF with itself and with LDL may improve the course of thrombotic microangiopathies, atherosclerosis, and other disorders with defective microvascular circulation.


Exploring the moderating effect of children's nutritional knowledge on the relationship between product evaluations and food choice.
Although the last decade has seen multiple attempts to increase consumers' nutritional knowledge in expectation that this will result in healthier diets, extant knowledge about the influence of nutritional knowledge on children's food choices remains scarce due to mixed empirical evidence and limited inquiry into the role of product evaluations on the consumption of less healthy foods. Furthermore, no research has examined whether nutritional knowledge can effectively moderate the relationship between product evaluations and food consumption, leaving a gap in our knowledge about potentially effective intervention strategies to curb childhood obesity. Using survey data from children aged 7-13 years and their parents (N = 354) recruited at an annual fair visited by families in South Australia, regressions were performed to examine how product evaluations are associated with the consumption of less healthy foods and whether nutritional knowledge reduces the strength of these associations at different ages (7-8 years, 9-10 years, and 11-13 years). While children did not view fast foods to be fun or healthy, there was a positive association between appealing taste, perceived social acceptability and consumption of less healthy foods. Higher nutritional knowledge weakened the relationship between product evaluations and consumption in children younger than 11. Parents with higher nutritional knowledge had children who tended to consume less healthy foods less frequently. Although older children (11-13 years) possessed higher nutritional knowledge, it was not associated with their consumption; instead, taste and perception of social acceptability were the only factors associated with frequent consumption of less healthy products. Practitioners are encouraged to test intervention strategies that concentrate on both product evaluations and nutritional knowledge to provide more effective outcomes. Further research about peer norms that endorse unhealthy eating is encouraged to facilitate a more comprehensive approach to unhealthy eating.


Enhancement of Berberine Hypoglycemic Activity by Oligomeric Proanthocyanidins.
This study investigated the possible enhancement of berberine's (BB) hypoglycemic activity by oligomeric proanthocyanidins (OPCs) and its underlying mechanism. The hypoglycemic activity of the studied compounds was evaluated in diabetic db/db mice. The cellular uptake and efflux of BB with or without OPCs were investigated using Caco-2 intestinal cells. A pharmacokinetic study of BB and OPCs was performed in Sprague Dawley (SD) mice by oral administration of the study compounds. Liquid chromatography⁻tandem mass spectrometry (LC⁻MS/MS) was employed to determine the cellular efflux, retention, and the serum concentrations of the compounds. The results revealed that OPCs considerably potentiated the hypoglycemic efficacy of BB in diabetic db/db mice. In the in vitro experiments, OPCs significantly inhibited the efflux and increased the uptake of the P-glycoprotein (P-gp) substrate rhodamine-123 (R123) and BB in Caco-2 intestinal cells. Moreover, OPCs substantially reduced the expression of P-gp in Caco-2 cells. The inhibition of BB efflux by OPCs was translated into the improved pharmacokinetics in vivo. When co-administered, OPCs obviously increased the average maximum concentration of BB in mice. In summary, this study demonstrated that combination of BB with OPCs could significantly improve the pharmacokinetics and hypoglycemic efficacy of BB, which is valuable for future exploration of the combination of BB and OPCs as oral hypoglycemic agents.


Tumor-Stroma Crosstalk in Bone Tissue: The Osteoclastogenic Potential of a Breast Cancer Cell Line in a Co-Culture System and the Role of EGFR Inhibition.
Although bone metastases represent a major challenge in the natural history of breast cancer (BC), the complex interactions involved have hindered the development of robust in vitro models. The aim of this work is the development of a preclinical model of cancer and bone stromal cells to mimic the bone microenvironment. We studied the effects on osteoclastogenesis of BC cells and Mesenchymal stem cells (MSC) cultured alone or in combination. We also analyzed: (a) whether the blockade of the Epithelial Growth Factor Receptor (EGFR) pathway modified their influence on monocytes towards differentiation, and (b) the efficacy of bone-targeted therapy on osteoclasts. We evaluated the osteoclastogenesis modulation of human peripheral blood monocytes (PBMC) indirectly induced by the conditioned medium (CM) of the human BC cell line SCP2, cultured singly or with MSC. Osteoclastogenesis was evaluated by TRAP analysis. The effect of the EGFR blockade was assessed by treating the cells with gefitinib, and analyzed with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Western Blot (WB). We observed that SCP2 co-cultured with MSC increased the differentiation of PBMC. This effect was underpinned upon pre-treatment of the co-culture with gefitinib. Co-culture of SCP2 with MSC increased the expression of both the bone-related marker Receptor Activator of Nuclear Factor κB (RANK) and EGFR in BC cells. These upregulations were not affected by the EGFR blockade. The effects of the CM obtained by the cells treated with gefitinib in combination with the treatment of the preosteoclasts with the bone-targeted agents and everolimus enhanced the inhibition of the osteoclastogenesis. Finally, we developed a fully human co-culture system of BC cells and bone progenitor cells. We observed that the interaction of MSC with cancer cells induced in the latter molecular changes and a higher power of inducing osteoclastogenesis. We found that blocking EGFR signaling could be an efficacious strategy for breaking the interactions between cancer and bone cells in order to inhibit bone metastasis.


The glycolytic enzyme, GPI, is a functionally conserved modifier of dopaminergic neurodegeneration in Parkinson's models.
Neurodegenerative diseases represent an increasing burden in our aging society, yet the underlying metabolic factors influencing onset and progression remain poorly defined. The relationship between impaired IGF-1/insulin-like signaling (IIS) and lifespan extension represents an opportunity to investigate the interface of metabolism with age-associated neurodegeneration. Using data sets of established DAF-2/IIS-signaling components in Caenorhabditis elegans, we conducted systematic RNAi screens in worms to select for daf-2-associated genetic modifiers of α-synuclein misfolding and dopaminergic neurodegeneration, two clinical hallmarks of Parkinson's disease. An outcome of this strategy was the identification of GPI-1/GPI, an enzyme in glucose metabolism, as a daf-2-regulated modifier that acts independent of the downstream cytoprotective transcription factor DAF-16/FOXO to modulate neuroprotection. Subsequent mechanistic analyses using Drosophila and mouse primary neuron cultures further validated the conserved nature of GPI neuroprotection from α-synuclein proteotoxicity. Collectively, these results support glucose metabolism as a conserved functional node at the intersection of proteostasis and neurodegeneration.


Systematic review of type 1 diabetes biomarkers reveals regulation in circulating proteins related to complement, lipid metabolism, and immune response.
Type 1 diabetes (T1D) results from an autoimmune attack of the pancreatic β cells that progresses to dysglycemia and symptomatic hyperglycemia. Current biomarkers to track this evolution are limited, with development of islet autoantibodies marking the onset of autoimmunity and metabolic tests used to detect dysglycemia. Therefore, additional biomarkers are needed to better track disease initiation and progression. Multiple clinical studies have used proteomics to identify biomarker candidates. However, most of the studies were limited to the initial candidate identification, which needs to be further validated and have assays developed for clinical use. Here we curate these studies to help prioritize biomarker candidates for validation studies and to obtain a broader view of processes regulated during disease development. This systematic review was registered with Open Science Framework ( https://doi.org/10.17605/OSF.IO/N8TSA ). Using PRISMA guidelines, we conducted a systematic search of proteomics studies of T1D in the PubMed to identify putative protein biomarkers of the disease. Studies that performed mass spectrometry-based untargeted/targeted proteomic analysis of human serum/plasma of control, pre-seroconversion, post-seroconversion, and/or T1D-diagnosed subjects were included. For unbiased screening, 3 reviewers screened all the articles independently using the pre-determined criteria. A total of 13 studies met our inclusion criteria, resulting in the identification of 266 unique proteins, with 31 (11.6%) being identified across 3 or more studies. The circulating protein biomarkers were found to be enriched in complement, lipid metabolism, and immune response pathways, all of which are found to be dysregulated in different phases of T1D development. We found 2 subsets: 17 proteins (C3, C1R, C8G, C4B, IBP2, IBP3, ITIH1, ITIH2, BTD, APOE, TETN, C1S, C6A3, SAA4, ALS, SEPP1 and PI16) and 3 proteins (C3, CLUS and C4A) have consistent regulation in at least 2 independent studies at post-seroconversion and post-diagnosis compared to controls, respectively, making them strong candidates for clinical assay development. Biomarkers analyzed in this systematic review highlight alterations in specific biological processes in T1D, including complement, lipid metabolism, and immune response pathways, and may have potential for further use in the clinic as prognostic or diagnostic assays.


The long and winding road: the journey taken by headache sufferers in search of help.
AimTo outline the pathways a cohort of first attendees to our headache clinics had taken over the years in search of explanations and treatment for their headaches. To establish a greater awareness of the shortcomings and failures in their medical journey in the hope that better headache management will emerge in primary care. BACKGROUND: At first attendance in primary care most headache sufferers will not receive a firm diagnosis. Treatments provided are often ineffective and so many patients embark on a somewhat random self-made journey searching for a remedy. If they reach a Headache Clinic the most common diagnoses are 'chronic migraine' and 'medication overuse headache'. They are either no better or worse than when their headaches first started despite their efforts. METHOD: We undertook a prospective questionnaire-based study of over 200 patients on first attendance at each of our headache clinics, three based in District General Hospitals and one in a tertiary referral centre. We documented the patients' headache characteristics, the 'burden' of their headaches, functional handicap and the financial costs incurred seeking help before referral. We also documented what our patients understood about their headache disorder and the treatments previously tried.FindingsMost patients had not been given a formal diagnosis in primary care and many remained unconvinced of the benign nature of their headache problem and wanted further investigations. A few had sought help from headache charities. Many had unrealistic attitudes to their problem and medication overuse was rife. A few patients had been offered triptans in primary care. Key deficiencies in the primary care management of these patients included failure to provide a formal headache diagnosis, inadequate understanding of the nature and mechanism of headaches and failure to follow a resilient management strategy. We provide a more effective management pathway in primary care.


Demographic predisposition to the evolution of eusociality: a hierarchy of models.
I present a hierarchy of models that illustrate, within the framework of inclusive fitness theory, how demographic factors can predispose a species to the evolution of eusociality. Delayed reproductive maturation lowers the inclusive fitness of a solitary foundress relative to that of a worker. Variation in age at reproductive maturity makes the worker strategy more profitable to some individuals than to others and thus predicts the coexistence of single-foundress and multiple-foundress nesting associations. Delayed reproductive maturation and variation in age at reproductive maturity also select for mixed reproductive strategies so that some individuals whose reproductive maturation is expected to be delayed can first act as workers and later switch over to the role of a queen or foundress. Assured fitness returns shows how identical mortality rates can have different consequences for workers and solitary nest foundresses because a solitary foundress will have to necessarily survive for the entire duration of development of her brood, whereas a worker can hope to get proportional fitness returns for short periods of work. In concert with assured fitness returns, delayed reproductive maturation and variation in age at reproductive maturity become more powerful in selecting for worker behavior, and mixed reproductive strategies become available to a wider range of individuals. These phenomena provide a consistently more powerful selective advantage for the worker strategy than do genetic asymmetries created by haplodiploidy.


Second-generation autologous chondrocyte implantation: results in patients older than 40 years.
Aging is responsible for degenerative changes in all cartilage elements, thus impairing its properties and healing potential. Most studies on surgical procedures for cartilage focus on young patients because these procedures are generally not considered suitable for older patients. To analyze the clinical outcome of cartilage lesion treatment using second-generation autologous chondrocyte implantation (ACI) techniques in patients more than 40 years old with no clear signs of osteoarthritis, to understand their real potential in relation to aging, the failure rate, and complications in older patients. Case series; Level of evidence, 4. Sixty-one patients with grade III to IV cartilaginous lesions of the condyles with no clear signs of osteoarthritis and a minimum age of 40 years were treated with second-generation ACI and prospectively evaluated at 5 years' follow-up. Twenty-two patients were treated with arthroscopic Hyalograft C implantation, and 39 underwent the open Chondro-Gide MACI procedure. A significant improvement in both subjective and objective evaluations was observed. The International Knee Documentation Committee (IKDC) subjective score improved from 36.8 ± 8.4 to 68.1 ± 21.8 at the final evaluation. The failure rate was 20%. A faster improvement was observed in the group treated with the arthroscopic Hyalograft C technique, whereas similar scores were found at the 24-month follow-up and final evaluation. A clinical improvement was found in patients more than 40 years old, who in most cases benefited from second-generation ACI with good results lasting at medium-term follow-up. However, the results were inferior with respect to those previously found for younger populations, and the failure rate at medium-term follow-up was also higher. These findings were consistent in the 2 treatment groups. The only difference was the faster recovery when the arthroscopic approach was used.


Human immunodeficiency virus (HIV)-1 infects human hepatic stellate cells and promotes collagen I and monocyte chemoattractant protein-1 expression: implications for the pathogenesis of HIV/hepatitis C virus-induced liver fibrosis.
Patients coinfected with human immunodeficiency virus (HIV) and hepatitis C virus (HCV) develop more rapid fibrosis than those infected with HCV only. In HIV/HCV-coinfected patients, fibrosis progression correlates with HIV RNA levels, suggesting a direct role of HIV in liver fibrogenesis. Chemokine (C-C motif) receptor 5 (CCR5) and cysteine-X-cysteine receptor 4 (CXCR4), the two major coreceptors required for HIV entry into cells, are expressed on activated hepatic stellate cells (HSCs), the principle fibrogenic cell type in the liver. We therefore examined whether HIV can infect HSCs, explored the potential mechanisms of viral entry, and assessed the impact of infection as reflected by the ability of HSCs to transfer virus to T lymphocytes and elicit a proinflammatory and profibrogenic response. We report that the laboratory-adapted viruses HIV-IIIB (CXCR4-tropic or X4) and HIV-BaL (CCR5-tropic or R5) and primary HIV isolates can infect both a human stellate cell line, LX-2, and primary human HSCs. HIV entry and gene expression in HSCs was confirmed using HIV-green fluorescent protein (GFP) expression viral constructs in the presence or absence of the reverse-transcriptase inhibitor azidothymidine. CD4 expression on a subset of primary HSCs was demonstrated using fluorescence-activated cell sorting and immunofluorescence staining. Blocking experiments in the presence of anti-CD4, anti-CXCR4, and anti-CCR5 revealed that HIV entry into HSCs is predominantly CD4/chemokine coreceptor-independent. HIV infection promoted HSC collagen I expression and secretion of the proinflammatory cytokine monocyte chemoattractant protein-1. Furthermore, infected LX-2 cells were capable of transferring GFP-expressing virus to T lymphocytes in a coculture system. Taken together, our results suggest a potential role of HIV in liver fibrosis/inflammation mediated through effects on HSCs. The role of early highly active antiretroviral therapy initiation in patients with HIV/HCV coinfection warrants further investigation.


Differential regulation of a family of apyrase genes from Medicago truncatula.
Four putative apyrase genes were identified from the model legume Medicago truncatula. Two of the genes identified from M. truncatula (Mtapy1 and Mtapy4) are expressed in roots and are inducible within 3 h after inoculation with Sinorhizobium meliloti. The level of mRNA expression of the other two putative apyrases, Mtapy2 and Mtapy3, was unaffected by rhizobial inoculation. Screening of a bacterial artificial chromosome library of M. truncatula genomic DNA showed that Mtapy1, Mtapy3, and Mtapy4 are present on a single bacterial artificial chromosome clone. This apyrase cluster was mapped to linkage group seven. A syntenic region on soybean linkage group J was found to contain at least two apyrase genes. Screening of nodulation deficient mutants of M. truncatula revealed that two such mutants do not express apyrases to any detectable level. The data suggest a role for apyrases early in the nodulation response before the involvement of root cortical cell division leading to the nodule structure.


[Prevention of infections caused by venous catheters in intensive care units].
The importance of the prevention of infections related to venous catheters comes from the frequent morbility which derives from these devices in ICU and the foresecable increase of infections which are secondary to them with the consequent increase in the load of Nursing work and costs in Spain, bacteriemias related to central catheters are 8%, under 5% for Swan-Ganz and almost inexistent for peripherals. Germs responsible for infectious incidences caused by catheters are basically Staphylococcus coagulase-negative and Staphylococcus aureus. The most affected veins are the jugular, followed by femoral, antecubital, subclavian and peripheral. The colonization of the patient's skin and the connections of catheters are the most frequent origin of infections and, since certain germs create defensive structures which make them more resistant to treatment, it is very important to carry out protocols of prevention and care which should encompass hand washing efficiency, daily care of the wound, use of suitable disinfectants and, very especially, the protection of catheter connections.


Assessing evidence supporting cannabis harm reduction practices for adolescents at clinical high-risk for psychosis: a review and clinical implementation tool.
Cannabis use is consistently associated with both increased incidence of frank psychotic disorders and acute exacerbations of psychotic symptoms in healthy individuals and people with psychosis spectrum disorders. Although there is uncertainty around causality, cannabis use may be one of a few modifiable risk factors for conversion to psychotic disorders in individuals with Clinical High Risk for Psychosis (CHR-P) syndromes, characterized by functionally impairing and distressing subthreshold psychotic symptoms. To date, few recommendations beyond abstinence to reduce adverse psychiatric events associated with cannabis use have been made. This narrative review synthesizes existing scientific literature on cannabis' acute psychotomimetic effects and epidemiological associations with psychotic disorders in both CHR-P and healthy individuals to bridge the gap between scientific knowledge and practical mental health intervention. There is compelling evidence for cannabis acutely exacerbating psychotic symptoms in CHR-P, but its impact on conversion to psychotic disorder is unclear. Current evidence supports a harm reduction approach in reducing frequency of acute psychotic-like experiences, though whether such interventions decrease CHR-P individuals' risk of conversion to psychotic disorder remains unknown. Specific recommendations include reducing frequency of use, lowering delta-9-tetrahydrocannabinol content in favor of cannabidiol-only products, avoiding products with inconsistent potency like edibles, enhancing patient-provider communication about cannabis use and psychotic-like experiences, and utilizing a collaborative and individualized therapeutic approach. Despite uncertainty surrounding cannabis' causal association with psychotic disorders, cautious attempts to reduce acute psychosis risk may benefit CHR-P individuals uninterested in abstinence. Further research is needed to clarify practices associated with minimization of cannabis-related psychosis risk.


Androgen-deprivation-associated bone disease.
Androgen deprivation therapy (ADT) remains a common treatment for prostate cancer, even in the nonmetastatic setting and in scenarios without evidence of efficacy. Increasing attention has focused on its adverse effects, of which bone disease in the form of osteoporosis and fractures has been one of the major concerns. Recently published articles are reviewed, focusing on ADT effects on bone and management of ADT-associated bone disease. A range of strategies directed at ADT-associated bone disease are available, including antiresorptive agents such as denosumab and bisphosphonates, as well as complementary approaches such as calcium and vitamin D supplementation, exercise regimens, and multifaceted interventions incorporating several approaches. Most interventions used bone mineral density as a surrogate outcome, despite compelling evidence that it inadequately captures fracture risk. The antiresorptive agents are clearly able to preserve bone mineral density in men on ADT, whereas other approaches have modest to no benefits. Unfortunately, despite intense research interest in this area, no approach has yet demonstrated a definitive and convincing reduction in clinically relevant fracture outcomes. This emphasizes the importance of restricting the use of ADT to settings in which its benefits are clearly established, in order to limit unnecessary complications.


Functioning of the Drosophila Wilms'-tumor-1-associated protein homolog, Fl(2)d, in Sex-lethal-dependent alternative splicing.
fl(2)d, the Drosophila homolog of Wilms'-tumor-1-associated protein (WTAP), regulates the alternative splicing of Sex-lethal (Sxl), transformer (tra), and Ultrabithorax (Ubx). Although WTAP has been found in functional human spliceosomes, exactly how it contributes to the splicing process remains unknown. Here we attempt to identify factors that interact genetically and physically with fl(2)d. We begin by analyzing the Sxl-Fl(2)d protein-protein interaction in detail and present evidence suggesting that the female-specific fl(2)d(1) allele is antimorphic with respect to the process of sex determination. Next we show that fl(2)d interacts genetically with early acting general splicing regulators and that Fl(2)d is present in immunoprecipitable complexes with Snf, U2AF50, U2AF38, and U1-70K. By contrast, we could not detect Fl(2)d complexes containing the U5 snRNP protein U5-40K or with a protein that associates with the activated B spliceosomal complex SKIP. Significantly, the genetic and molecular interactions observed for Sxl are quite similar to those detected for fl(2)d. Taken together, our findings suggest that Sxl and fl(2)d function to alter splice-site selection at an early step in spliceosome assembly.


Material and monetary flows of construction and demolition waste and assessment on physical and environmental properties of illegally dumped construction and demolition waste in Hanoi.
The main aim of this study is to investigate the material and monetary flows of CDW management and to characterize the distribution of illegally dumped CDW in Hanoi. Construction and demolition waste management has become a source of much concern to the urban authorities and citizens of big cities in Vietnam. It is estimated that 3000 t of CDW were generated per day from construction and demolition activities in Hanoi, but only 45% of the CDW was received at official landfills, while 55% of the CDW was disposed of elsewhere. The consequences of improper waste management are potentially alarming. The study conducted interviews to identify the material and cash flow associated with licensed and unlicensed contractors in CDW classification, transportation, treatment, and disposal, to characterize the distribution of illegally dumped CDW in two districts in Hanoi (urban and suburban districts), and to assess the composition of dumped CDW and environmental assessment of illegally dumped CDW by chemical analyses such as leaching and content tests. The study concluded that illegal dumping was performed mostly by unlicensed private companies. The illegally dumped CDW was mostly composed of mixed materials such as concrete, bricks, stones, and some hazardous materials such as asbestos and gypsum were found. The environmental concern of illegally dumped CDW was mostly dust, blockage of water ways, and inundation of increased suspended solids, whereas the heavy metal leaching concentration of all samples was below the environmental standards in Vietnam.


The unchanging face of Lennox-Gastaut syndrome in adulthood.
Lennox-Gastaut syndrome (LGS) is a severe childhood-onset epileptic encephalopathy characterized by the presence of multiple types of intractable seizures, cognitive impairment, and specific electroencephalogram (EEG) patterns. The aim of this study was to investigate the electroclinical features of patients with LGS during adulthood. We retrospectively identified the medical records of 20 patients aged over 18 years with a diagnosis of LGS from 3896 patients with epilepsy. Thirteen (65 %) patients were male. The mean age of the patients was 23.4 ± 7.1 (min-max; 18-43) years, and the mean follow-up period was 5.6 ± 4.5 (min-max; 1-14) years. The etiology was identified in 11 (55 %) patients. None of the patients achieved seizure freedom. The most prevalent seizure types were atypical absences in 14 (70 %) patients, tonic seizures in 13 (65 %) patients, and atonic seizures in 11 (55 %) patients. One (5 %) patient was diagnosed as having psychogenic non-epileptic seizures. Mental retardation was reported in all patients and only half of them could walk independently. All patients had drug-resistant seizures and 16 (80 %) patients were on polytherapy. A vagus nerve stimulator was implanted into ten (50 %) patients and five reported 50-80 % seizure reduction. Ketogenic diet was administered to two (10 %) patients and epilepsy surgery was performed in two (10 %) patients with no significant benefit. Paying attention to all factors of seizure outcomes, cognitive impairment, and ambulatory status, all patients were dependent on caregivers for daily living abilities. LGS has life-long persistence with poor outcomes, even during adulthood.


Activity limitations and compensatory mechanism use following limited wrist fusion.
To document the activity limitations experienced by patients who had undergone a 4-corner wrist fusion, and the compensatory mechanisms they use in daily life. Patients completed 2 copies of the Adelaide Questionnaire, a measure with a standardized section and an individualized section. The test-retest reliability of the questionnaire was evaluated. Twenty-five patients were recruited to the study, and 21 completed both questionnaires. Excellent test-retest reliability was gained for both the standardized and individualized sections of the Adelaide Questionnaire. Patients with 4-corner wrist fusions report activity limitations following surgery, particularly with daily tasks that involve hand/forearm rotation and grip strength. Various compensatory mechanisms are used by the majority of patients. The impact of these mechanisms on activity limitations varies between patients, but often decreases impact of the activity limitations on everyday life.


[Aminosalicylates and aspirin for colonic cancer: from anti-inflammatory to antineoplastic drugs?].
The aim of this article is to review potential antineoplastic properties of anti-inflammatory compounds commonly used in various inflammatory diseases such as aminosalicylates, aspirin and other nonsteroidal drugs. Starting from experimental and epidemiologic evidence showing prophylaxis and/or tumor regression/suppression, specific antineoplastic actions especially the inhibition of cyclooxygenase-(COX)dependent and COX-independent steps including the role of transcription factor (NFkappaB) in the cell cycle regulation are reviewed. In addition other mechanisms by which these drugs may exert antitumor effects, also may be important such as induction of apoptosis of cancer cells and/or inhibition of potentially carcinogenic oxidative DNA damage. Based on this knowledge potential clinical implications are discussed.


Intellectual, behavioral, and personality correlates of violent vs. non-violent juvenile offenders.
The overall aim of this study was to examine the relationship between offender status (violent vs. nonviolent) and selected predictor variables from personality, behavioral, and intellectual domains. The two main sub goals were (a) to determine which variables from these domains were most closely associated with offender status, and (b) to construct a stepwise logistic regression model that could help identify which juveniles were more likely to be incarcerated for violent vs. nonviolent offenses. The participants for this investigation were juvenile offenders referred to the Juvenile Court Assessment Center by the Juvenile Justice Division of the Eleventh Judicial Circuit. The court-ordered assessment included the following measures: (a) The Millon Adolescent Clinical Inventory (MACI), (b) the Behavior Assessment System for Children (BASC), (c) the Peabody Picture Vocabulary Test-Third Edition (PPVT-III), (d) the Wide Range Achievement Test-Third Edition (WRAT-III), (e) the Kaufman Brief Intelligence Test (K-BIT), and (f) records of school achievement. The ten variables that had the strongest association with offender status were entered into the stepwise logistic regression analysis; five of these strategically chosen predictor variables accurately differentiated violent from nonviolent offenders 86.3% of the time. Reading Percentile (β=-.051), PPVT-III (β=-.059), MACI-Inhibition (β=-.033), MACI-Eating Dysfunction (β=.051), and BASC-Sense of Inadequacy (β=-.072). Gender differences were explored.


Suppression of giardiasis during the intestinal phase of trichinosis in the mouse.
The interaction of the intestinal phases of Giardia muris and Trichinella spiralis was investigated in Swiss albino mice. Intraoesophageal inoculation of G. muris cysts seven days before, or seven days after, similar inoculation of T. spiralis larvae resulted in significant reduction in the numbers of Giardia trophozoites in small bowel and Giardia cysts in stools. This effect was not observed when G. muris cysts were administered after resolution of the intestinal phase of trichinosis. Giardiasis had no effect on trichinosis as assessed by numbers of adult worms in small bowel and larvae in skeletal muscles. Studies of small bowel morphology showed that the intestinal phase of trichinosis was associated with increased numbers of inflammatory cells in the lamina propria, a significant increase in Paneth cells in crypts, and a marked reduction in the villus:crypt ratio of jejunum. These observations suggest that the intestinal phase of trichinosis induced environmental changes in small bowel, perhaps related to inflammation, which resulted in suppression of proliferation of Giardia trophozoites.


Creation of a genetic system for analysis of the phagocyte respiratory burst: high-level reconstitution of the NADPH oxidase in a nonhematopoietic system.
The phagocyte nicotinamide adenine dinucleotide phosphate (reduced form) (NADPH) oxidase was functionally reconstituted in monkey kidney COS-7 cells by transfection of essential subunits, gp91(phox), p22(phox), p47(phox), and p67(phox). COS-7 cells express the essential small guanosine 5'-triphosphatase, Rac1. Transgenic COS-phox cells were capable of arachidonic acid-induced NADPH oxidase activity up to 80% of that of human neutrophils, and of phorbol myristate acetate (PMA)-induced activity up to 20% of that of neutrophils. Expression of all 4 phox components was required for enzyme activity, and enzyme activation was associated with membrane translocation of p47(phox), p67(phox), and Rac1. Expression of p47(phox) Ser303Ala/Ser304Ala or Ser379Ala phosphorylation-deficient mutants resulted in significantly impaired NAPDH oxidase activity, compared with expression of wild-type p47(phox) or the p47(phox) Ser303Glu/Ser304Glu phosphorylation mimic, suggesting that p47(phox) phosphorylation contributes to enzyme activity in the COS system, as is the case in neutrophils. Hence, COS-phox cells should be useful as a new whole-cell model that is both capable of high-level superoxide production and readily amenable to genetic manipulation for investigation of NADPH oxidase function. PMA-elicited superoxide production in COS-phox cells was regulated by activation of protein kinase C (PKC) and Rac. Although COS-7 cells differ from human neutrophils in PKC isoform expression, transient expression of major neutrophil isoforms in COS-phox cells did not increase PMA-induced superoxide production, suggesting that endogenous isoforms were not rate limiting. Val204 in p67(phox), previously shown to be required for NADPH oxidase activity under cell-free conditions, was found to be essential for superoxide production by intact COS-phox cells, on the basis of transfection studies using a p67(phox) (Val204Ala) mutant.


Psychological improvements associated with behavioral and drug treatment of urge incontinence in older women.
The purpose of this study was to explore changes in psychological distress associated with behavioral treatment and drug treatment for urge incontinence in community-dwelling older women. Participants were 197 ambulatory, nondemented women (aged 55 years or older) with persistent urge urinary incontinence. Participants were patients in a randomized clinical trial comparing biofeedback-assisted behavioral treatment, drug treatment with oxybutynin chloride, and a placebo-control condition. Psychological distress was measured before and after treatment using the Hopkins Symptom Checklist (SCL-90-R). Multivariate and univariate analyses of variance showed that the two treatment groups and the control group had similar significant improvements on the nine subscales and the global severity index. Analysis of individual SCL-90-R subscale scores revealed trends suggesting that behavioral treatment tended to produce the largest improvements. The reductions of distress were not correlated consistently with reduction of incontinence. The results of this study showed that psychological distress was significantly reduced after treatment, regardless of the type of treatment.


Analysis of HIV-1 Gag protein interactions via biotin ligase tagging.
We have examined the interactions of wild-type (WT) and matrix protein-deleted (ΔMA) HIV-1 precursor Gag (PrGag) proteins in virus-producing cells using a biotin ligase-tagging approach. To do so, WT and ΔMA PrGag proteins were tagged with the Escherichia coli promiscuous biotin ligase (BirA*), expressed in cells, and examined. Localization patterns of PrGag proteins and biotinylated proteins overlapped, consistent with observations that BirA*-tagged proteins biotinylate neighbor proteins that are in close proximity. Results indicate that BirA*-tagged PrGag proteins biotinylated themselves as well as WT PrGag proteins in trans. Previous data have shown that the HIV-1 Envelope (Env) protein requires an interaction with MA for assembly into virions. Unexpectedly, ΔMA proteins biotinylated Env, whereas WT BirA*-tagged proteins did not, suggesting that the presence of MA made Env inaccessible to biotinylation. We also identified over 50 cellular proteins that were biotinylated by BirA*-tagged PrGag proteins. These included membrane proteins, cytoskeleton-associated proteins, nuclear transport factors, lipid metabolism regulators, translation factors, and RNA-processing proteins. The identification of these biotinylated proteins offers new insights into HIV-1 Gag protein trafficking and activities and provides new potential targets for antiviral interference. We have employed a novel strategy to analyze the interactions of the HIV-1 structural Gag proteins, which involved tagging wild-type and mutant Gag proteins with a biotin ligase. Expression of the tagged proteins in cells allowed us to analyze proteins that came in close proximity to the Gag proteins as they were synthesized, transported, assembled, and released from cells. The tagged proteins biotinylated proteins encoded by the HIV-1 pol gene and neighbor Gag proteins, but, surprisingly, only the mutant Gag protein biotinylated the HIV-1 Envelope protein. We also identified over 50 cellular proteins that were biotinylated, including membrane and cytoskeletal proteins and proteins involved in lipid metabolism, nuclear import, translation, and RNA processing. Our results offer new insights into HIV-1 Gag protein trafficking and activities and provide new potential targets for antiviral interference.


Magnetic resonance imaging in patients with dental implants: a clinical report.
Magnetic resonance imaging is used more and more frequently as a diagnostic tool. Because high magnetic fields are used, knowledge on how these will affect implanted material and the patient is of great importance. Ferromagnetic properties of implant materials are seldom described by the manufacturer, but a doctor requesting magnetic resonance imaging of a patient must know about these properties. Not only is the composition of an alloy important, but also the size and shape of the metallic material as well as its position in the body. Implants from the Brånemark System were tested; findings indicated that the implants were not influenced when exposed to magnetic resonance imaging. The artifacts caused by the implants were minor and did not jeopardize the evaluation of the scans. However, magnet keepers attached to the implants were found to cause major artifacts and must be removed before an implant patient is referred for a magnetic resonance imaging examination.


Increased urinary nerve growth factor as a predictor of persistent detrusor overactivity after bladder outlet obstruction relief in a rat model.
We evaluated urinary nerve growth factor as a predictive factor for persistent detrusor overactivity after bladder outlet obstruction relief in a rat model. A total of 50 female Sprague-Dawley(R) rats were divided into 2 groups, including 10 sham operated controls and 40 with bladder outlet obstruction. Obstruction was induced by partial urethral ligation and relieved by ligation removal after 3 weeks. Voided urine was collected before bladder outlet obstruction at time 1, 3 weeks after obstruction onset at time 2 and 3 weeks after obstruction relief at time 3. Cystometry was done in awake rats at times 2 and 3. Bladder tissue was harvested at time 3. Urinary and bladder tissue nerve growth factor was measured by enzyme-linked immunosorbent assay with results adjusted based on creatinine concentration. In 16 rats in which detrusor overactivity disappeared after bladder outlet obstruction relief (group 1) urinary nerve growth factor/creatinine significantly increased from time 1 to 2 and significantly decreased from time 2 to 3 (p = 0.001 and 0.003, respectively). In 8 rats with persistent detrusor overactivity despite obstruction removal (group 2) urinary nerve growth factor/creatinine significantly increased from time 1 to 2 but did not change from time 2 to 3 (p = 0.012 and 0.123, respectively). These rats with persistent detrusor overactivity also had significantly higher urinary nerve growth factor/creatinine at time 1 than controls and group 1 (p = 0.015 and 0.005, respectively). Changes in urinary nerve growth factor may reflect detrusor overactivity, as diagnosed on 2 consecutive cystometries. Increased urinary nerve growth factor before bladder outlet obstruction may predict persistent detrusor overactivity after obstruction relief.


Effectiveness of early part-time sick leave in musculoskeletal disorders.
The importance of staying active instead of bed rest has been acknowledged in the management of musculoskeletal disorders (MSDs). This emphasizes the potential benefits of adjusting work to fit the employee's remaining work ability. Despite part-time sick leave being an official option in many countries, its effectiveness has not been studied yet. We have designed a randomized controlled study to assess the health effects of early part-time sick leave compared to conventional full-day sick leave. Our hypothesis is that if work time is temporarily reduced and work load adjusted at the early stages of disability, employees with MSDs will have less disability days and faster return to regular work duties than employees on a conventional sick leave. The study population will consist of 600 employees, who seek medical advice from an occupational physician due to musculoskeletal pain. The inclusion requires that they have not been on a sick leave for longer than 14 days prior to the visit. Based on the physician's judgement, the severity of the symptoms must indicate a need for conventional sick leave, but the employee is considered to be able to work part-time without any additional risk. Half of the employees are randomly allocated to part-time sick leave group and their work time is reduced by 40-60%, whereas in the control group work load is totally eliminated with conventional sick leave. The main outcomes are the number of days from the initial visit to return to regular work activities, and the total number of sick leave days during 12 and 24 months of follow-up. The costs and benefits as well as the feasibility of early part-time sick leave will also be evaluated. This is the first randomised trial to our knowledge on the effectiveness of early part-time sick leave compared to conventional full-time sick leave in the management of MSDs. The data collection continues until 2011, but preliminary results on the feasibility of part-time sick leave will be available already in 2008. The increased knowledge will assist in better decision making process regarding the management of disability related to MSDs. International Standard Randomised Controlled Trial Number Register, register number ISRCTN30911719.


Fertility after salpingostomy following mechanically produced hydrosalpinx in rabbits.
Microsurgical salpingostomy results in 90% of tubes remaining patent following surgery. Although pregnancy rates have improved to a slight extent, the percentage of patients having live babies after salpingostomy is still disappointing. The discrepancy between patency rates and pregnancy rates seems to be due mainly to long standing tubal damage after the original infection. Possibly, raised intraluminal pressure from accumulated fluid may be a factor. Mechanically produced hydrosalpinges in rabbits show similar morphological characteristics to human hydrosalpinges (Vasquez et al., 1981, Otubu et al., 1984). This rabbit model was used in this study to examine the relationship between the severity of these changes and fertility after salpingostomy. Mechanical hydrosalpinges were produced in thirty mature New Zealand white rabbits by double clip application. After a period varying from 8 to 52 weeks of clip application, cuff salpingostomy and ampullary-isthmic anastomosis was done. One week after surgery, the animals were mated with bucks of proven fertility. There were pregnancies in all the uterine horns on the unoperated side (control) in all animals. There were pregnancies on the operated side in only two animals giving a pregnancy rate of 6.7%. A total of sixteen tubes were patent out of thirty operated, giving a patency rate of 53.3%. Adhesion was a major problem. We conclude that fertility is reduced after salpingostomy in mechanically produced hydrosalpinges in rabbits. The significance of this finding is discussed.


Medicinal products liability of the pharmacists: an overview of some emerging legal issues in Nigeria.
There is no doubt that medicinal products are under strict control and regulation with the aim of protecting the consumers and hence promoting public health. However, there have been incidences in Nigeria where the use of some of these products have resulted to injury and even death. And in view of the alarming rate of adulteration of drugs and other related products and especially with the increase in the resort to numerous herbal products in Nigeria now, manufacturers, physicians, pharmacists as well as the consumers of medicinal products need to be abreast with their obligations, rights and remedies as the case may be. Also, the increased complexity and expanded role of the pharmacists in the drug-use process may bring about an increased exposure to liability as a result of injuries arising from their actions. This paper aims to highlight the potential liability of the pharmacist and educate the pharmacy community about product liability laws that have arisen from the expanded role of pharmacists in the healthcare delivery system.


Metastatic Breast Carcinoma-Associated Fibroblasts Have Enhanced Protumorigenic Properties Related to Increased IGF2 Expression.
The microenvironment of metastatic breast cancer is incompletely characterized, despite prior evidence that it plays a key role in the biology of metastasis. A major component of the tumor stroma is the carcinoma-associated fibroblast (CAF), which has been shown to communicate with other stromal and cancer cells to create a protumorigenic milieu. Our study was designed to characterize human CAFs from different metastatic sites. We collected eight carcinoma-associated fibroblasts (mCAFs) from different metastatic sites and compared them with CAFs from primary tumors (pCAFs) and with normal breast fibroblasts (NFs). Molecular profiles and effects on breast cancer cell growth, on response to doxorubicin and on T-cell proliferation were compared. We observed marked differences in mCAFs compared with pCAFs and NFs with respect to in vitro proliferation and effects on breast cancer cell migration, spheroid growth, invasion, response to doxorubicin, and in vivo tumor growth. We found marked transcriptomic differences between mCAFs and pCAFs, including increased expression of IFN-related genes and IGF2 in the former. Cluster analysis revealed two groups of mCAFs, with the liver mCAFs clustering together, with increased PDGFA expression. Treatment with an antibody against insulin-like growth factors (BI836845) inhibited growth of mixed mCAF-tumor cell xenografts in vivo. Also, mCAFs had a suppressive effect on T-cell proliferation. This is the first comparative analysis of a set of CAFs from metastatic sites in breast cancer. It revealed a marked protumorigenic effect in these mCAFs, which occurs in part through increased expression of IGF2.


Response of hyperhomocysteinemia to folic acid supplementation in patients with end-stage renal disease.
Elevated concentrations of homocysteine are associated with an increased risk for cardiovascular disease. Reasons for elevated homocysteine concentrations are folate or vitamin B12 deficiency, renal disease or genetic abnormalities. A high prevalence of hyperhomocysteinemia is found in patients with end-stage renal disease (ESRD). Since these patients are also at increased risk for vitamin deficiency, a supplementation study comparing two doses of folic acid was performed in patients with ESRD treated with maintenance hemodialysis or with peritoneal dialysis. Patients undergoing hemodialysis (n = 70) or peritoneal dialysis (n = 12) were supplemented with 2.5 mg or 5 mg folic acid (three times per week after each dialysis treatment) for four weeks in a parallel study design. In 20 hemodialysis patients, the effect of folic acid withdrawal was observed after four weeks. Both supplementation schemes reduced homocysteine to a similar extent (35%) but did not normalize homocysteine concentrations in the majority of patients. Dialysis also had a strong homocysteine lowering effect. After supplementation, 74% of the hemodialysis patients had post-dialysis homocysteine concentrations within the reference range (<16 micromol/l). Homocysteine concentrations remained decreased in 20 patients four weeks after withdrawal of folic acid supplementation. It is concluded that supplementation with 2.5 or 5 mg folic acid has a similar effect on homocysteine concentrations to supplementation regimens using 15 mg folic acid supplements. In contrast to the effect of folic acid supplementation in subjects with normal renal function, folic acid supplementation does not normalize homocysteine concentrations in ESRD patients.


Seasonal dynamics and distribution of house dust mites in China.
House dust mites are widely distributed in the human habitat and work environment and produce very powerful allergens. The most important allergy-causing mites found in homes worldwide are the house dust mites Dermatophagoides farinae and D. pteronyssinus and the storage mite Blomia tropicalis. It is important to know which mite species are present in a geographical area when performing diagnostic testing and prescribing immunotherapy. We classified the breeding situations of house dust mites in dwellings in northern China. Mites are detectable in March and their number increases from April or May, reaching a peak from July to September. The seasonal distribution of different acaroid mite species may differ: temperature, humidity, and eating habits were the major limiting factors determining species composition and diversity of acaroid mite communities in house ecosystems; comparing to the field and the forest, in human living area including house and working place, acaroid mites showed less bio-diversity.


Intervascular anastomoses created by an endovascular approach: technical aspects and initial results in an animal study.
The current article describes the initial results after the creation of intervascular connections with use of an exclusively endovascular approach. Connections of two vessels were performed in the thoracic and abdominal areas with use of a kinematic needle without traversing a solid organ. The materials developed specifically for this technique are described. The procedure was carried out in 11 animals and consisted of bringing together two vascular structures with use of magnets, performing a puncture from the lumen of one vessel to that of the other, and inserting a prosthesis between the two. The prosthesis has a biconical morphology and is made with a 0.016-inch monofilament of nitinol. Its most outstanding feature is that, when it is dilated with a balloon, it shortens and "rolls up," flattening its ends. This allows good fixation to the vessel wall, avoiding the protrusion of metal into the lumen of the native vessel. On four occasions, the aorta was connected to another nearby vessel: the abdominal aorta to the inferior vena cava (IVC; n = 1), the ascending aorta to the trunk of the pulmonary artery (n = 1), and the descending aorta to the left pulmonary artery (n = 2). On another four occasions, two veins were connected: the portal vein and the IVC. Finally, on three occasions, the right pulmonary artery was connected to the superior vena cava. The connection was safely and accurately performed with passage of a guide wire in all cases. In two experiments, the prosthesis was too short and leakage with massive bleeding was observed after a successful initial deployment of the prosthesis Intervascular anastomoses created by an endovascular approach are feasible in the authors' experimental model for several different vessel pairings.


Actions of prostaglandin E2 on rat supraoptic neurones.
Prostaglandins (PGs) have been implicated in the regulation of vasopressin (VP) and oxytocin (OT) release in response to various stimuli. To examine the site and mechanism of actions of PGs, we studied effects of PGE2 and PG-receptor agonists on supraoptic nucleus (SON) neurones of rat hypothalamic slice preparations using extracellular recording and whole-cell patch-clamp techniques. PGE2 modulated the electrical activity of more than 80% of the neurones studied. The effects of PGE2 on both phasic and non-phasic neurones were mostly excitatory, and dose-dependent. The effects of PGE2 were mimicked by PGF2alpha or the FP agonist, fluprostenol, whereas PGD2 or the selective EP, IP or TP agonist was less effective or had no effect. The effects of PGE2 were unaffected by the EP1 antagonist, SC-51322, but reduced to 80% of control by the EP1/FP/TP antagonist, ONO-NT-012, which reduced the effects of fluprostenol to 32% of control. Moreover, some neurones responsive to PGE2 did not respond to fluprostenol. Patch-clamp analysis in SON slice preparations revealed that PGE2 at 10(-6) M depolarized the membrane potential by 3.9+/-0.3 mV from the resting membrane potential of -58.4+/-2.2 mV in the current-clamp mode. In the voltage-clamp mode, PGE2 induced inward currents at a holding potential of -70 or -80 mV, while it did not affect spontaneous excitatory postsynaptic currents. PGE2 induced currents also in dissociated SON neurones and the reversal potential of the currents was -35.5+/-0.9 mV, which was similar to that of currents induced by fluprostenol. These results suggest that SON neurones possess at least two types of PG receptors, FP receptors and EP receptors of a subclass different from EP1, EP2, or EP3, and that activation of these receptors leads to the opening of nonselective cation channels, membrane depolarization and increase of the action potential discharge.


Confocal Fluorescence Microscopy Investigation for the Existence of Subdomains within Protein Storage Vacuoles in Soybean Cotyledons.
In legumes, the seed storage proteins accumulate within specialized organelles called protein storage vacuoles (PSVs). In several plant species, PSVs are differentiated into subdomains that accumulate different kinds of proteins. Even though the existence of subdomains is common in cereals and legumes, it has not been reported in soybean PSVs. The two most abundant seed proteins of soybean, 7S and 11S globulins, have different temporal accumulation patterns and exhibit considerable solubility differences that could result in differential accretion of these proteins within the PSVs. Here, we employed confocal fluorescent microscopy to examine the presence or absence of subdomains within the soybean PSVs. Eosin-stained sections of FAA-fixed paraffin embedded soybean seeds, when viewed by confocal fluorescence microscopy, revealed the presence of intricate subdomains within the PSVs. However, fluorescence immunolabeling studies demonstrated that the 7S and 11S globulins were evenly distributed within the PSVs and failed to corroborate the existence of subdomains within the PSVs. Similarly, confocal scanning microscopy examination of free-hand, vibratome and cryostat sections also failed to demonstrate the existence of subdomains within PSVs. The subdomains, which were prominently seen in PSVs of FAA-fixed soybean seeds, were not observed when the seeds were fixed either in glutaraldehyde/paraformaldehyde or glutaraldehyde. Our studies demonstrate that the apparent subdomains observed in FAA-fixed seeds may be a fixation artifact.


Butyrylcholinesterase: association with the metabolic syndrome and identification of 2 gene loci affecting activity.
Plasma cholinesterase activity is known to be correlated with plasma triglycerides, HDL- and LDL-cholesterol, and other features of the metabolic syndrome. A role in triglyceride metabolism has been proposed. Genetic variants that decrease activity have been studied extensively, but the factors contributing to overall variation in the population are poorly understood. We studied plasma cholinesterase activity in a sample of 2200 adult twins to assess covariation with cardiovascular risk factors and components of the metabolic syndrome, to determine the degree of genetic effects on enzyme activity, and to search for quantitative trait loci affecting activity. Cholinesterase activity was lower in women than in men before the age of 50, but increased to activity values similar to those in males after that age. There were highly significant correlations with variables associated with the metabolic syndrome: plasma triglyceride, HDL- and LDL-cholesterol, apolipoprotein B and E, urate, and insulin concentrations; gamma-glutamyltransferase and aspartate and alanine aminotransferase activities; body mass index; and blood pressure. The heritability of plasma cholinesterase activity was 65%. Linkage analysis with data from the dizygotic twin pairs showed suggestive linkage on chromosome 3 at the location of the cholinesterase (BCHE) gene and also on chromosome 5. Our results confirm and extend the connection between cholinesterase, cardiovascular risk factors, and metabolic syndrome. They establish a substantial heritability for plasma cholinesterase activity that might be attributable to variation near the structural gene and at an independent locus.


[Gastric and duodenal mucosal function in peptic ulcer patients exposed to endoscopic laser therapy and sanatorium-health resort factors].
A comparative study of gastric and duodenal bulb mucosa has been performed in 138 patients with ulcer before and after treatment. The patients were treated with either He-Ne laser or copper steam laser alone vs combination of laser therapy with spa treatment. The most favourable was the complex including green spectrum laser in combination with administration of Shira Lake mineral water and electrophoresis of this water.


Justifying discrimination against Muslim immigrants: out-group ideology and the five-step social identity model.
This study examines how Geert Wilders, leader of the far-right Party For Freedom (PVV) in the Netherlands, justifies discriminatory measures for Muslim citizens. Wilders' contributions to four parliamentary debates and newspaper articles are analysed. The analysis shows that Wilders consistently makes a distinction between Islam as a belief system and Muslims as a group of people. Islam is defined as external to the West and as a major threat to the virtuous nature of the in-group. Defending and preserving Western liberal values against Islam is construed as a moral imperative. It is further shown how the distinction between Islam and Muslims functions to ward off accusations of prejudice and discrimination. It is concluded that social psychologists studying prejudice and discrimination should pay more attention to the distinction between person categories and ideological categories, and to political leadership.


Mammography rates for 20 community-based family practices in Ontario: a full practice audit.
Many Canadian women 50 to 69 years of age do not have a mammogram within the recommended screening interval of every two years. Recent data suggest that over 50% of Canadian women did not have a time-appropriate mammogram and that not having a family physician was a significant factor associated with suboptimal screening. This study reviewed medical charts of 20 family physicians' practices to examine their mammography screening patterns. Medical charts of all women between 52 and 71 years of age in 20 family practices were examined for mammography reports between September 2003 and June 2004. Across the 20 practices, 3,430 charts of eligible women 52 to 71 years of age were reviewed (mean per practice = 173 women; ranging from 38 to 385). The two-year time-appropriate mammography rate was 58.8%. The screening rates ranged from 25% to 76% across 20 practices. Four practices attained a 70% or greater time-appropriate screening rate. When we extended the time-appropriate frame to 36 months, the overall mammography rate increased to 70.0%. Practice size, method of remuneration for patient care, use of an electronic medical record, gender or age of physician, practice setting, use of Ontario Breast Screening Program (OBSP) were not found to be significantly associated with mammography screening rates. Mammography rates within the recommended two-year interval for women who have a regular family physician are suboptimal. The rates for women in this study, all of whom have a family physician, were only slightly higher than those reported elsewhere for women without one. Further studies are required to uncover and overcome barriers to optimal mammography screening rates.


Managing patients with dual diagnosis in psychiatric practice.
To focus on recent research that may influence clinical practice in relation to patients with dual diagnosis disorders. Harmful substance use is a heightened risk with bipolar disorder. Self-medication with substances of abuse for anxiety is linked with greater risk of developing anxiety disorders, particularly social anxiety disorder. Antisocial and schizotypal personality disorders were particularly linked with chronicity in substance use disorders. There are sex differences in responses to psychological approaches for dual disorders involving alcohol. Integrated dual diagnosis treatment for youth is not conclusive but shows promise. Online therapy is viable for adult patients with dual diagnosis. Structured interventions reduce the risk of opioid misuse amongst those with chronic pain, who are identified as at high risk. We have confirmation that clinicians should be particularly vigilant in monitoring for substance use problems early in anxiety disorders and mood disorders and that certain personality disorders are linked with substance use chronicity. Practitioners can incorporate specific therapy approaches for dual disorders that appear to have advantages over treatment as usual.


Gamete recognition in mice depends on the cleavage status of an egg's zona pellucida protein.
At fertilization, mouse sperm bind to the zona pellucida (which consists of glycoproteins ZP1, ZP2, and ZP3) that surrounds eggs. A ZP2 cleavage model of gamete recognition requires intact ZP2, and a glycan release model postulates that zona glycans are ligands for sperm. These two models were tested by replacing endogenous protein with ZP2 that cannot be cleaved (Zp2(Mut)) or with ZP3 lacking implicated O glycans (Zp3(Mut)). Sperm bound to two-cell Zp2(Mut) embryos despite fertilization and cortical granule exocytosis. Contrary to prediction, sperm fertilized Zp3(Mut) eggs. Sperm at the surface of the zona pellucida remained acrosome-intact for more than 2 hours and were displaced by additional sperm. These data indicate that sperm-egg recognition depends on the cleavage status of ZP2 and that binding at the surface of the zona is not sufficient to induce sperm acrosome exocytosis.


What do patients want from their psychiatrist? A cross- sectional questionnaire based exploratory study from Karachi.
The aspects of consultation that are important for psychiatric patients have always remained a less acknowledged area. The aim of this study was to identify these aspects. A Cross-sectional, questionnaire based study was carried out in a psychiatry outpatient clinic of two tertiary care hospitals in a developing country. The patients were asked to fill out the questionnaire containing a total of 11 close-ended questions plus 1 open-ended question. They graded them as not important, important, very important or do not know. Non-psychotic patients aged 18 and above, visiting the clinic were recruited into the study before they went in for their first consultation. The response rate of patients was 84%. More than 90% wanted the doctor to tell them the cause of their illness, talk to them about their condition, provide symptomatic relief, let them know that how long their illness would last and make the final decision about their treatment plan. Less than 20% wanted to be part of a support network. A significant 82% wanted talking therapy as part of their treatment plan. The three issues, most important for patients were: the doctor should listen to them, make the final decision about treatment and provide symptomatic relief. Only 20% wanted to be a part of patients' support group.


Early diffusion weighted imaging and expression of heat shock protein 70 in newborn pigs with hypoxic ischaemic encephalopathy.
To establish a cerebral hypoxia ischaemic model in piglets and to explore the early diffusion weighted imaging (DWI) as well as the expression of heat shock protein 70 (HSP70) with hypoxic ischaemic encephalopathy (HIE). Twenty four 3 day old piglets were permanently ligated common carotid arteries bilaterally and ventilated with 3% oxygen for 30 minutes, and their brains were examined at three hours, six hours, and 24 hours after hypoxic ischaemia with T2 weighted images and diffusion weighted images. Apparent diffusion coefficient (ADC) values were measured and HSP70 expression was detected in the central and peripheral regions of lesions. Abnormal signal intensity was detected on DWI and ADC maps in three hypoxic ischaemic groups. ADC values in the central lesions rapidly decreased, whereas ADC values in the peripheral regions reduced prominently at 24 hours after hypoxic ischaemia. There were significant differences (p<0.01) between ADC values of the central regions and the peripheral regions of lesions. The number of HSP70 positive cells was low at three hours, raised at the highest peak at six hours, and then rapidly decreased. There was statistical difference between HSP70 positive cells in the central regions and those in peripheral regions (p<0.01). DWI may identify more early lesions, and improve conspicuity in the acute setting. ADC values can be used as an objective measure for hypoxic ischaemic injury. Tissue reversibility can be further reflected according to the information of ADC values and HSP70 immunohistochemical staining.