Localized electric field of plasmonic nanoplatform enhanced photodynamic tumor therapy.
Near-infrared plasmonic nanoparticles demonstrate great potential in disease theranostic applications. Herein a nanoplatform, composed of mesoporous silica-coated gold nanorods (AuNRs), is tailor-designed to optimize the photodynamic therapy (PDT) for tumor based on the plasmonic effect. The surface plasmon resonance of AuNRs was fine-tuned to overlap with the exciton absorption of indocyanine green (ICG), a near-infrared photodynamic dye with poor photostability and low quantum yield. Such overlap greatly increases the singlet oxygen yield of incorporated ICG by maximizing the local field enhancement, and protecting the ICG molecules against photodegradation by virtue of the high absorption cross section of the AuNRs. The silica shell strongly increased ICG payload with the additional benefit of enhancing ICG photostability by facilitating the formation of ICG aggregates. As-fabricated AuNR@SiO2-ICG nanoplatform enables trimodal imaging, near-infrared fluorescence from ICG, and two-photon luminescence/photoacoustic tomography from the AuNRs. The integrated strategy significantly improved photodynamic destruction of breast tumor cells and inhibited the growth of orthotopic breast tumors in mice, with mild laser irradiation, through a synergistic effect of PDT and photothermal therapy. Our study highlights the effect of local field enhancement in PDT and demonstrates the importance of systematic design of nanoplatform to greatly enhancing the antitumor efficacy.


Autism spectrum disorder prevalence and associations with air concentrations of lead, mercury, and arsenic.
Lead, mercury, and arsenic are neurotoxicants with known effects on neurodevelopment. Autism spectrum disorder (ASD) is a neurodevelopmental disorder apparent by early childhood. Using data on 4486 children with ASD residing in 2489 census tracts in five sites of the Centers for Disease Control and Prevention's Autism and Developmental Disabilities Monitoring (ADDM) Network, we used multi-level negative binomial models to investigate if ambient lead, mercury, and arsenic concentrations, as measured by the US Environmental Protection Agency National-Scale Air Toxics Assessment (EPA-NATA), were associated with ASD prevalence. In unadjusted analyses, ambient metal concentrations were negatively associated with ASD prevalence. After adjusting for confounding factors, tracts with air concentrations of lead in the highest quartile had significantly higher ASD prevalence than tracts with lead concentrations in the lowest quartile (prevalence ratio (PR) = 1.36; 95 '% CI: 1.18, 1.57). In addition, tracts with mercury concentrations above the 75th percentile (>1.7 ng/m(3)) and arsenic concentrations below the 75th percentile (≤0.13 ng/m(3)) had a significantly higher ASD prevalence (adjusted RR = 1.20; 95 % CI: 1.03, 1.40) compared to tracts with arsenic, lead, and mercury concentrations below the 75th percentile. Our results suggest a possible association between ambient lead concentrations and ASD prevalence and demonstrate that exposure to multiple metals may have synergistic effects on ASD prevalence.


Root and bone response to the proximity of a mini-implant under orthodontic loading.
To determine the histological reaction of the root and bone as a mini-implant approaches the root. Two kinds of mini-implants were inserted into the buccal alveolar bone of 4 beagles (2 males and 2 females). The specimens were classified as the near-root group, the PDL contact group, the root contact group, and the root perforation group. Cementum resorption, dentin resorption, cementum repair, cementum growth, ankylosis, root cracking, and root fracture were assessed as the implant neared the root. The incidence of root resorption increased when the mini-implant was less than 0.6 mm from the root in the near-root group and PDL contact group. Root cracking and root fracture occurred in the root contact group and root perforation group. Bone resorption and ankylosis were observed in some specimens. However, some specimens of the PDL contact group and root contact group had cementum growth or little root resorption despite proximity to the root. In the root perforation group, root resorption and ankylosis occurred on the side opposite the insertion. There is a risk of root contact and severe tissue damage from a thick mini-implant and the drilling procedure, either of which can induce root resorption or ankylosis. Use of smaller mini-implants may reduce root contact and tissue damage. However, the small mini-implant may need enhancement of its stability.


The effect of naproxen on fever in patients with advanced gynecologic malignancies.
The antipyretic action of naproxen has been reported as sufficiently selective for neoplasm-related fever such that the use of this agent has been recommended to distinguish neoplastic from infectious fever. The antipyretic effect of naproxen was evaluated in gynecologic oncology patients with advanced pelvic malignancies and fever without obvious source of infection (suspected neoplastic fever). Naproxen (250 mg orally every 8 hr) was given to 12 patients with (i) a daily temperature greater than 38.3 degrees C, (ii) fever for at least 3 days, (iii) no evidence of infection on physical exam, (iv) negative results of blood and urine cultures, and (v) a chest roentgenogram negative for pneumonia. Ten of the 12 patients initially received a minimum of 3 days of empiric antibiotic therapy without resolution of fever. Within 24 hr of starting naproxen therapy, 10 patients' (83%) fever responded: Eight patients (80%) had a complete lysis of fever and two had partial lysis (20%). Temperature response was accompanied by subjective improvement in patient malaise and fatigue. Naproxen therapy was continued for 5-7 days in these patients, and chemotherapy was administered to those patients scheduled to receive it. Two patients did not respond to naproxen therapy in 24 hr; thus, it was stopped and the fever workup was continued. Of these two patients, one was eventually diagnosed with bacteremia after multiple negative blood cultures and initially no response to antibiotics. Naproxen is clinically useful in the palliation of fever-related symptoms in gynecologic oncology patients with suspected neoplastic fever. Naproxen may also allow the limitation of extensive fever workups and prolonged empiric antibiotic therapy in these patients, and prevent delays in systemic therapy or supportive care.


A 13 kDa fragment is responsible for the hydrophobic aggregation of brain G4 acetylcholinesterase.
Proteinase K treatment of the bovine brain acetylcholinesterase (AChE) releases a hydrophobic fragment of 13 kDa, which is entirely responsible for the aggregation of the G4 AChE in the absence of detergent. This observation provides evidence that the 13 kDa fragment, which comes from a previously identified 20 kDa subunit, is directly involved in the attachment of the G4 AChE to brain membranes. A model for the organization of the different sub-domains of the hydrophobic anchor of the G4 AChE is presented.


Homing of intestinal immune cells.
The homing of immune cells into the intestinal mucosa, the gut-associated lymphoid tissue or the mesenteric lymph nodes involves a complex process of molecular events that is dependent on cell type and cell maturation. Key factors that collectively determine the homing of leukocytes and their interaction with resident endothelial, epithelial, stromal and immune cells are interactions between integrins or selectins with their tissue adhesion molecules as well as chemokine receptors and their ligands. The organization of the small and large intestinal tissue and the mucosa associated lymphoid tissue as well as the presence or absence of inflammatory stimuli influence the homing of intestinal immune cells. The homing pattern of intestinal dendritic cells and CD4+ T cells and its role for the pathogenesis and regulation of inflammatory bowel disease are discussed.


Calcium dysregulation combined with mitochondrial failure and electrophysiological maturity converge in Parkinson's iPSC-dopamine neurons.
Parkinson's disease (PD) is characterized by a progressive deterioration of motor and cognitive functions. Although death of dopamine neurons is the hallmark pathology of PD, this is a late-stage disease process preceded by neuronal dysfunction. Here we describe early physiological perturbations in patient-derived induced pluripotent stem cell (iPSC)-dopamine neurons carrying the GBA-N370S mutation, a strong genetic risk factor for PD. GBA-N370S iPSC-dopamine neurons show an early and persistent calcium dysregulation notably at the mitochondria, followed by reduced mitochondrial membrane potential and oxygen consumption rate, indicating mitochondrial failure. With increased neuronal maturity, we observed decreased synaptic function in PD iPSC-dopamine neurons, consistent with the requirement for ATP and calcium to support the increase in electrophysiological activity over time. Our work demonstrates that calcium dyshomeostasis and mitochondrial failure impair the higher electrophysiological activity of mature neurons and may underlie the vulnerability of dopamine neurons in PD.


Helper T cell-dependent human B cell differentiation mediated by a mycoplasmal superantigen bridge.
Experimentally induced murine graft-vs.-host disease may be characterized by hypergammaglobulinemia, autoantibody formation, and immune complex-mediated organ system damage that mimics SLE. These autoimmune phenomena are mediated by abnormal Th-B cell cooperation, across MHC disparities, in which donor-derived allospecific Th cells recognize and interact with MHC class II antigens on the surface of recipient B cells. Microbial toxins, termed superantigens, which bind to MHC class II molecules and activate selected T cells based on TCR variable gene usage, may induce a similar form of Th-B cell interaction. In the present study, we generated and characterized human Th cell lines reactive with the Mycoplasma arthritidis superantigen (MAM). The essential observation is that resting human B cells bind MAM and present it to superantigen-reactive autologous or allogeneic Th cells, resulting in both Th cell activation and a consequent polyclonal Ig response by the superantigen-bearing B cells.


Automatic identification of bird targets with radar via patterns produced by wing flapping.
Bird identification with radar is important for bird migration research, environmental impact assessments (e.g. wind farms), aircraft security and radar meteorology. In a study on bird migration, radar signals from birds, insects and ground clutter were recorded. Signals from birds show a typical pattern due to wing flapping. The data were labelled by experts into the four classes BIRD, INSECT, CLUTTER and UFO (unidentifiable signals). We present a classification algorithm aimed at automatic recognition of bird targets. Variables related to signal intensity and wing flapping pattern were extracted (via continuous wavelet transform). We used support vector classifiers to build predictive models. We estimated classification performance via cross validation on four datasets. When data from the same dataset were used for training and testing the classifier, the classification performance was extremely to moderately high. When data from one dataset were used for training and the three remaining datasets were used as test sets, the performance was lower but still extremely to moderately high. This shows that the method generalizes well across different locations or times. Our method provides a substantial gain of time when birds must be identified in large collections of radar signals and it represents the first substantial step in developing a real time bird identification radar system. We provide some guidelines and ideas for future research.


Deep neural networks for interpreting RNA-binding protein target preferences.
Deep learning has become a powerful paradigm to analyze the binding sites of regulatory factors including RNA-binding proteins (RBPs), owing to its strength to learn complex features from possibly multiple sources of raw data. However, the interpretability of these models, which is crucial to improve our understanding of RBP binding preferences and functions, has not yet been investigated in significant detail. We have designed a multitask and multimodal deep neural network for characterizing in vivo RBP targets. The model incorporates not only the sequence but also the region type of the binding sites as input, which helps the model to boost the prediction performance. To interpret the model, we quantified the contribution of the input features to the predictive score of each RBP. Learning across multiple RBPs at once, we are able to avoid experimental biases and to identify the RNA sequence motifs and transcript context patterns that are the most important for the predictions of each individual RBP. Our findings are consistent with known motifs and binding behaviors and can provide new insights about the regulatory functions of RBPs.


Prion protein expression alters APP cleavage without interaction with BACE-1.
The prion protein (PrP) and the beta-site amyloid precursor protein (APP) cleaving enzyme 1 (BACE-1) are both copper binding proteins, but are associated with two separate neurodegenerative diseases. The role of BACE-1 in the formation of beta-amyloid has made it a major target in attempts to reduce the formation of beta-amyloid in Alzheimer's diseases. However, the suggestion that PrP, normally associated with prion diseases, binds to BACE-1 and reduces its activity has led to the suggestion that the study of this interaction could be of considerable importance to Alzheimer's disease. We therefore undertook to investigate the possible interaction of these two proteins physically and at the level of transcription, translation and APP cleavage. Our findings suggest that mature PrP and BACE-1 do not physically interact, but that altered PrP expression results in altered BACE-1 protein expression and promoter activity. Additionally, overexpression of PrP results in increased cleavage of APP in contrast to previous datas suggesting a reduction. Our findings suggest that any relation between PrP and BACE-1 is indirect. Altered expression of PrP causes changes in the expression of many other proteins which may be as a result of altered copper metabolism.


Oxytocin system dysfunction as a common mechanism underlying metabolic syndrome and psychiatric symptoms in schizophrenia and bipolar disorders.
There is growing interest in using intranasal oxytocin (OT) to treat social dysfunction in schizophrenia and bipolar disorders (i.e., psychotic disorders). While OT treatment results have been mixed, emerging evidence suggests that OT system dysfunction may also play a role in the etiology of metabolic syndrome (MetS), which appears in one-third of individuals with psychotic disorders and associated with increased mortality. Here we examine the evidence for a potential role of the OT system in the shared risk for MetS and psychotic disorders, and its prospects for ameliorating MetS. Using several studies to demonstrate the overlapping neurobiological profiles of metabolic risk factors and psychiatric symptoms, we show that OT system dysfunction may be one common mechanism underlying MetS and psychotic disorders. Given the critical need to better understand metabolic dysregulation in these disorders, future OT trials assessing behavioural and cognitive outcomes should additionally include metabolic risk factor parameters.


Effective elements of school health promotion across behavioral domains: a systematic review of reviews.
Most school health education programs focus on a single behavioral domain. Integrative programs that address multiple behaviors may be more efficient, but only if the elements of change are similar for these behaviors. The objective of this study was to examine which effective elements of school health education are similar across three particular behavioral domains. A systematic review of reviews of the effectiveness of school-based health promotion programs was conducted for the domains of substance abuse, sexual behavior, and nutrition. The literature search spanned the time period between 1995 and October 2006 and included three databases, websites of review centers and backward search. Fifty-five reviews and meta-analyses met predetermined relevance and publication criteria and were included. Data was extracted by one reviewer and checked by a second reviewer. A standardized data extraction form was used, with detailed attention to effective elements pertaining to program goals, development, content, methods, facilitator, components and intensity. Two assessors rated the quality of reviews as strong, moderate or weak. We included only strong and moderate reviews in two types of analysis: one based on interpretation of conflicting results, the other on a specific vote-counting rule. Thirty six reviews were rated strong, 6 moderate, and 13 weak. A multitude of effective elements was identified in the included reviews and many elements were similar for two or more domains. In both types of analysis, five elements with evidence from strong reviews were found to be similar for all three domains: use of theory; addressing social influences, especially social norms; addressing cognitive-behavioral skills; training of facilitators; and multiple components. Two additional elements had positive results in all domains with the rule-based method of analysis, but had inconclusive results in at least one domain with the interpretation-based method of analysis: parent involvement and a larger number of sessions. Five effective elements of school health promotion were found to be similar across the three behavioral domains examined (substance abuse, sexual behavior, nutrition). An integrative program that addresses the three domains seems feasible. The five elements are primary candidates to include in programs targeting these behaviors.


Nanostructured SBA-15 silica as an adjuvant in immunizations with hepatitis B vaccine.
To evaluate the applicability of SBA-15 silica as an adjuvant in immunizations with purified particles of the viral protein HBsAg, the main component of hepatitis B vaccine, Butang®, produced by Instituto Butantan. BALB/c mice orally or subcutaneously received 0.5 μg of HBsAg adsorbed/encapsulated to SBA-15 or adsorbed to Al(OH)3. To assess the secondary immune response, a subcutaneous booster was administered 30 days after the first immunization. Individual serum and fecal samples of each group were periodically collected for specific antibody titration by ELISA. Analysis of secretory IgA showed that mice orally primed with HBsAg on SBA-15 had increased levels of specific antibodies in primary and secondary immune responses. Specific serum IgA and IgG titers in HBsAg:SBA-15-orally immunized mice reached higher levels after the booster, demonstrating the effectiveness of oral vaccination with the use of silica. All immunized groups showed higher IgG1 levels. Our results clearly indicate the promising use of SBA-15 as an adjuvant, especially in oral immunizations.


Role of extracorporeal shock wave therapy in management of Peyronie's disease: A preliminary report.
Peyronie's Disease (PD) is a disease causing psycho social trauma to the patient. Multiple treatment options are available with variable results. Extra Corporeal Shock Wave Therapy (ESWT) is a new insight into the non invasive modality of management. It focuses on the mechanism of inducing angiogenesis in the penile cavernous tissue. The aim of the study is to determine the role of ESWT in the management of PD. The objectives include demonstrating the improvement in mean International Index of Erectile Function Score (IIEFS), improvement in pain score by Visual Analogue Scale (VAS), change in cavernosal artery flow on colour penile Doppler, reduction in plaque size, and improvement in penile curvature degree after the therapy. 30 patients, between 25-65 years, who were non responders to conservative line of management, were treated with ESWT. The results were evaluated at baseline and 18-24 weeks after the therapy. ESWT significantly improves the cavernosal artery velocity, thereby supporting the theory of angiogenesis. ESWT improves all the domains of IIEF including Erectile Function, Sexual Desire, Sexual Satisfaction, Orgasm and Overall Satisfaction. There is a significant improvement in the pain and penile curvature, and reduction in the plaque size. No adverse effects have been recorded. ESWT offers a safe, minimally invasive, OPD based option to the management of the patients of PD in the stable phase of the disease. Patients who do not respond to the conservative line of management can be really benefited by ESWT.


Comparison of fast-neutron contamination of different models of Siemens medical linacs with CR-39 film.
Nowadays, radiotherapy has an important role in the treatment of cancer. The use of medical linacs in radiotherapy can have risks for patients. When radiotherapy is performed with photons with energies higher than 8 MeV, due to the photonuclear reaction of photons with various components in the head of the accelerator, the neutron is produced. This imposes an unwanted neutron dose to the patient. The purpose of this study is evaluation and comparison of fast-neutron contamination with increasing of field size and depth for Siemens Primus (15 MV), Siemens Primus Plus (18 MV), and Siemens Artiste (15 MV) linacs. Neutron dosimetry was carried out with CR-39 films, as a fast-neutron dosimeter, using chemical etching technique. Measurements were performed in depths of 0.5, 2, 3, and 4 cm and source-to-surface distance of 100 cm. Field sizes were 10 cm × 10 cm and 30 cm × 30 cm. The results of measurements showed that, with increasing depth, equivalent dose is reduced. In addition, fast-neutron equivalent dose decreases with increasing the field size. Siemens Primus Plus had the highest neutron contamination in comparison with the two other linacs. Deeper tissues receive less fast-neutron doses. In radiation therapy with high-energy photon beams, neutron dose delivered to the patients should be taking into account.


The Rift Valley fever virus nonstructural protein NSs is phosphorylated at serine residues located in casein kinase II consensus motifs in the carboxy-terminus.
The S segment of Rift Valley fever virus (Bunyaviridae, Phlebovirus) codes for two proteins, the nucleoprotein N and the nonstructural protein NSs. The NSs protein is a phosphoprotein of unknown function that is localized in the cytoplasm and the nuclei of infected cells where it forms filamentous structures. To characterize further the protein expressed in VC10 cells infected with the MP12 strain, we analyzed its phosphorylation states and showed that phosphorylated forms were found in both compartments. Cytoplasmic and nuclear NSs were phosphorylated only at serine residues. Phosphopeptide mapping and molecular analysis of mutants obtained by site-directed mutagenesis allowed us to map the major phosphorylation sites of nuclear and cytoplasmic forms of NSs to serine residues 252 and 256, located at the carboxy-terminus in consensus sequences for casein kinase II. A similar map was obtained when the protein was purified from mosquito cells infected with MP12. In addition, we showed that the purified unphosphorylated NSs protein expressed from pET-NSs plasmid in a coupled transcription-translation reaction containing Escherichia coli S30 extracts did not possess autophosphorylation activity but was phosphorylated in vitro after incubation with recombinant casein kinase II.


High 10-year survival rate in patients with early, untreated prostatic cancer.
To learn about the natural history of untreated, early-stage prostatic cancer. Cohort study with a mean follow-up of 123 months (range, 81 to 165 months). Population-based, regionally well defined. A consecutive sample of 223 patients (98% of all eligible) with early-stage (T0-2, NX, M0), initially untreated prostatic cancer. Progression-free, disease-specific, and overall survival. Need for palliative and terminal care. Patients with tumor progression were hormonally treated (orchiectomy or estrogens) if they had symptoms. After complete follow-up, only 19 (8.5%) of the 223 patients had died of prostate cancer and 105 (85%) of a total of 124 deaths were from other causes. The 10-year, disease-specific survival rate was 86.8% (95% confidence interval, 80.7% to 92.9%) and was equally high (87.9%) in a subgroup of 58 patients who met current indications for radical prostatectomy. The progression-free, 10-year survival rate was 53.1% (95% confidence interval, 44.2% to 62.0%). In 50 of 76 patients, local growth provided the only evidence of progression, and endocrine treatment was generally successful in these cases. Following an initial increase, the rate of disease progression and death from prostate cancer decreased during the last years of follow-up. The low disease-specific mortality rate, especially in patients with highly and moderately differentiated tumors, means that any local or systemic therapy intended for patients with early prostatic cancer must be evaluated in clinical trials with untreated controls for comparison.


Juveniles' knowledge of the court process: results from instruction from an electronic source.
Our study first determined what juveniles know about the juvenile court process. Second, it evaluated a DVD designed to be a systematic and simple way to improve this knowledge. A pre- and posttest design was used with two pilot samples and two samples from the population of interest. A sample from a juvenile detention center (n = 118) was the focus of this study. Initial knowledge of the court process was quite low for the detention sample (pretest M = 64.0%, SD = 14.2%). All samples experienced a significant improvement of knowledge after watching the DVD. Youth in the detention sample had a mean improvement from pretest to posttest of 6.4% (SD = 11.9%), with mean scores at posttest being 70.3% (SD = 17.4%). Respondents varied in their performance on different question topics, scoring the lowest on questions related to what happens at juvenile court hearings. The social and demographic variables of age, race, gender, grades in school, number of previous arrests, and the number of times the respondent had been to court were evaluated through regression analysis. Age and race were found to be significantly related to pretest scores, and race was significantly related to improvement scores.


Mobile Monitoring Framework to Design Parameterized and Personalized m-Health Applications According to the Patient's Diseases.
The development of personalized mobile monitoring applications is a complex work. Currently, the most of applications for patients monitoring through mobile devices, is not developed considering the particular characteristics of each patient, but these applications have been developed taking into account a general behavior depending on the diseases instead of the own patients. The diseases manifest different symptoms depending on the patient situation. Mary and John (hypothetic patients) have diabetes, but the same measurement of glucose for each one affects their health in a different way. This paper describes a framework that allows the development of mobile applications, personalized for each patient, in such a way that even if they have the same disease, the application will respond to the individual needs of each patient.


First Report of Ramularia cercosporelloides on Carthamus tinctorius in Northwestern Mexico.
Severe yield losses caused by an unidentified fungal disease occurred on safflower in Sonora, Mexico from 2001 to 2006. Leaf spots were pale at the beginning and became sunken lesions, spots turned brown, and diseased tissue became necrotic. Under continuous presence of dew, new infections occurred and the number of lesions increased, coalesced, and eventually the entire leaf and plant turned brown and dried up. The fungus appears as a whitish mold covering the lesions. Observations with a dissecting microscope revealed fungal growth on both leaf surfaces. Spots had minute, gray-to-pink tufts emerging from the host tissues. Stromata were roughly spherical, 35 to 55 μm in diameter, developed under the epidermis near the edge of the spots from which conidiophores arose. Fascicles of conidiophores emerged through stomata from colorless or slightly yellowish stroma and were simple, colorless, or slightly yellowish, as much as 85 μm long and 2.5 to 3 μm wide, with a pigmented scar at the tip. Conidia, formed in chains at scar sites on conidiophores, were colorless, obclavate, 0 to 1 septate, approximately 24 to 32 μm long, and 4.5 to 7 μm wide at the broadest part with a pigmented scar either at the base or at both ends. On the basis of symptoms and fungal morphology, the pathogen was identified as Ramularia cercosporelloides U. Braun & Crous (=Cercosporella carthami) (1). Seven specimens were deposited at the Uppsala University Herbarium as Nos. UPS F-119998 to 120004. Conidia were transferred to water agar plates from symptomatic leaves after 8 days in a humid chamber. Ten single conidia were plated onto a Septoria tritici medium (4 g each of malt extract, yeast extract, and sucrose, and 18 g of agar per liter of water). Colonies of the fungus were white-to-light pink with irregular margins and very slow in growth. Inoculum was produced by transferring 2 ml of distilled water containing conidia onto petri plates filled with Septoria medium. Plates were incubated at 18°C for 12 days. Water suspension was amended with two drops of Tween 20 per liter of inoculum. Pathogenicity of five isolates was confirmed by spraying a suspension of 1.0 × 105 conidia/ml onto five pots of four direct-seeded adult plants of cv. S-518 per isolate. Plants were kept in a dew chamber (20°C) for 48 h under 16 h of darkness and 8 h of light and then in a greenhouse (20 to 24°C). After 2 weeks, leaves developed the characteristic spots, and R. cercosporelloides was isolated from symptomatic tissue. To our knowledge, this is the first report of R. cercosporelloides on safflower, not only in Mexico, but also on the American continent. Reference: (1) U. Braun. A monograph of Cercosporella, Ramularia and allied genera (Phytopathogenic Hyphomycetes). Vol 2. IHW-Verlag. Eching bei Munchen, 1998.


Couples' experiences with prostate cancer: focus group research.
To explore the experiences of couples living with prostate cancer, the impact of the illness on their quality of life, their ability to manage symptoms, and their suggestions for interventions that would help them to improve their daily experiences. Descriptive, qualitative. Six focus groups were used to obtain the data; two were patient-only groups, two were spouse-caregiver groups, and two were dyad groups. The focus groups were conducted at two comprehensive cancer centers in the midwestern region of the United States. 42 participants: 22 men with prostate cancer and 20 spouse-caregivers. Focus group discussions were tape-recorded, and the content was analyzed. Quality of life, symptom experience, and areas for intervention. Four major themes emerged from the data: enduring uncertainty, living with treatment effects, coping with changes, and needing help. Participants had a need for information and support. Both men and spouse-caregivers felt unprepared to manage treatment effects. Symptoms had a broad effect on couples, not just men. Positive effects of the illness, as well as negative effects, emerged from the themes. Attention needs to be given to methods of providing information and support to couples coping with prostate cancer. Both patients and partners need to be included in discussions about the effect of the illness and treatments so that both can feel more prepared to manage them.


Multicomponent blood analysis by near-infrared Raman spectroscopy.
We demonstrate the use of Raman spectroscopy to measure the concentration of many important constituents (analytes) in serum and whole blood samples at physiological concentration in vitro across a multipatient data set. A near-infrared (830-nm) diode laser generates Raman spectra that contain superpositions of Raman signals from different analytes. Calibrations for glucose, cholesterol, urea, and other analytes are developed by use of partial least-squares cross validation. We predict six analytes in serum with significant accuracy in a 66-patient data set, using 60-s spectra. The calibrations are shown to be fairly robust against system drift over the span of seven weeks. In whole blood, a preliminary analysis yields accurate predictions of some of the same analytes and also hematocrit. The results hold promise for potential medical applications.


Vitamin E attenuates crystal formation in rat kidneys: roles of renal tubular cell death and crystallization inhibitors.
We previously reported that oxidative stress and renal tubular damage occur in chronic hyperoxaluric rats. However, the in vivo responses of renal epithelial cells after vitamin E administration and their correlations with calcium oxalate (CaOx) crystal formation have not been evaluated. Male Wistar rats received 0.75% ethylene glycol (EG) for 7, 21, or 42 days to induce CaOx deposition (EG group). Another group of EG-treated rats received 200 mg kg(-1) of vitamin E intraperitoneally (EG+E group) to evaluate its effect on hyperoxaluria. Urinary electrolytes and biochemistry and levels of lipid peroxides and enzymes were examined, together with serum vitamin E levels. Levels of the tubular markers, alpha and mu glutathione S-transferase, proliferating cell nuclear antigen (PCNA), osteopontinin (OPN), and Tamm-Horsfall protein (THP) were also measured, and TUNEL staining was performed to examine the viability of the tubular epithelium. There were no significant differences between the two age-matched controls either untreated or given vitamin E. Compared to untreated controls, tubular cell death was increased at all time points in EG rats with a gradual increase in CaOx crystals, whereas the number of PCNA-positive cells was only significantly increased on day 21. In EG+E rats, tubular cell death was decreased compared to the EG group, and cell proliferation was seen at all time points, while CaOx crystal deposition was decreased, but hyperoxaluria, urinary lipid peroxides, and enzymuria were unaffected. Vitamin E supplement prevented the loss of OPN and THP in renal tissues by EG and the reduction in their levels in the urine. The beneficial effect of vitamin E in reducing CaOx accumulation is due to attenuation of tubular cell death and enhancement of the defensive roles of OPN and THP.


Results of a randomized, population-based study of biennial screening using serum prostate-specific antigen measurement to detect prostate carcinoma.
The purpose of the current study was to evaluate the effectiveness of a prostate carcinoma screening program in which serum prostate-specific antigen (PSA) levels were measured. From a group of 20,000 men born between January 1, 1930, and December 31, 1944, 10,000 men were randomized into a screening group and 10,000 were randomized into a control group. Patients in the screening group were invited to undergo initial PSA testing between 1995 and 1996 and then were invited to receive testing every second year thereafter for 8 years (for a total of 4 PSA tests). Men with PSA levels > or =3 ng/mL (or > or =2.54 ng/mL, in the third and fourth screening rounds) were invited to undergo clinical investigation, which included sextant biopsy of the prostate. By linking to the regional cancer registry, the authors were able to obtain the true and expected incidence rates for the screening and control groups. The screening participation rate was high (73%). A total of 884 malignancies have been detected to date, with 640 having been detected in the screening group. There was an early and marked shift toward more favorable disease stage and grade for malignancies detected on repeat screening. In the fourth screening round, only 2 of 82 detected malignancies were classified as advanced disease. Of the 227 screen-detected tumors on which surgery was performed, only 20 (8.8%) had small volume (<0.2 cm3). Forty-three interval malignancies were detected, but only five were accompanied by symptoms. At 8 years, the cumulative disease incidence rate among screening participants was 7.3%, compared with 2.4% in the control arm. The incidence rate observed in the screening population corresponds to the cumulative incidence rate observed in the Swedish male population at age 72 years. Biennial PSA screening was very successful in diagnosing prostate carcinoma at an early stage, when curative treatment typically is effective. In addition, the results regarding interval malignancies were favorable. Thus, decreased mortality should be observed on long-term follow-up. The lead time associated with screening appears to fall within the range described in earlier studies involving frozen sera (i.e., 5-9 years).


Stagnation Detection with Randomized Local Search.
Recently a mechanism called stagnation detection was proposed that automatically adjusts the mutation rate of evolutionary algorithms when they encounter local optima. The so-called SD-(1+1) EA introduced by Rajabi and Witt (2022) adds stagnation detection to the classical (1+1) EA with standard bit mutation. This algorithm flips each bit independently with some mutation rate, and stagnation detection raises the rate when the algorithm is likely to have encountered a local optimum. In this article, we investigate stagnation detection in the context of the k-bit flip operator of randomized local search that flips k bits chosen uniformly at random and let stagnation detection adjust the parameter k. We obtain improved runtime results compared with the SD-(1+1) EA amounting to a speedup of at least (1-o(1))2πm, where m is the so-called gap size, that is, the distance to the next improvement. Moreover, we propose additional schemes that prevent infinite optimization times even if the algorithm misses a working choice of k due to unlucky events. Finally, we present an example where standard bit mutation still outperforms the k-bit flip operator with stagnation detection.


Establishment of spatial pattern.
An overview and perspective are presented of mechanisms for the development of spatial pattern in animal embryos. It is intended both for new entrants to developmental biology and for specialists in other fields, with only a basic knowledge of animal life cycles being required. The first event of pattern formation is normally the localization of a cytoplasmic determinant in the egg, either during oogenesis or post-fertilization. Following cleavage to a multicellular stage, some cells contain the determinant and others do not. The determinant confers a specific developmental pathway on the cells that contain it, often making them the source of the first extracellular signal, or inducing factor. Inducing factors often form concentration gradients to which cells respond by up or downregulating genes at various concentration thresholds. This enables an initial situation consisting of two cell states (with or without the determinant) to generate a multistate pattern. Multiple rounds of gradient signaling, interspersed with phases of morphogenetic movements, can generate a complex pattern using a small number of signals and responding genes. Development proceeds in a hierarchical manner, with broad body subdivisions being specified initially, and becoming successively subdivided to give individual organs and tissues composed of multiple cell types in a characteristic arrangement. Double gradient models can account for embryonic regulation, whereby a similarly proportioned body pattern is formed following removal of material. Processes that are involved at the later stages include the formation of repeating structures by the combination of an oscillator with a gradient, and the formation of tissues with one cell type scattered in a background of another through a process called lateral inhibition. This set of processes make up a 'developmental toolkit' which can be deployed in various sequences and combinations to generate a very wide variety of structures and cell types.


Trajectories of anxiety in a population sample of children: clarifying the role of children's behavioral characteristics and maternal parenting.
This study pursued three goals. The first goal was to explore children's trajectories of anxiety from age 6 to 12 using a representative community sample. The second goal was to assess the link between certain behavioral characteristics assessed in kindergarten (i.e., inattention, hyperactivity, aggressiveness, and low prosociality) and these trajectories. The third goal was to determine whether certain aspects of maternal parenting (i.e., warmth and discipline) could moderate the association between these characteristics and the trajectories of anxiety. A population sample of 2,000 children (1,001 boys, 999 girls) participated in this longitudinal study. Developmental trajectory analyses allowed us to identify four trajectory groups: low, low-increasing, high-declining, and high anxiety groups. Moreover, multinomial logistic regressions revealed a profile of children at risk of developing high anxiety symptoms (i.e., high group), characterized by sociofamily adversity, inattention, and low prosociality in the classroom. Hyperactivity was also found in this profile, but only for children exposed to a mother who showed little affective warmth. Finally, mothers' high level of discipline increased the odds of belonging to the high anxiety group. The results are discussed in relation to studies examining the association among anxiety, behavioral characteristics, and parenting during childhood.


A novel antiangiogenic effect for telomerase-specific virotherapy through host immune system.
Soluble factors in the tumor microenvironment may influence the process of angiogenesis; a process essential for the growth and progression of malignant tumors. In this study, we describe a novel antiangiogenic effect of conditional replication-selective adenovirus through the stimulation of host immune reaction. An attenuated adenovirus (OBP-301, Telomelysin), in which the human telomerase reverse transcriptase promoter element drives expression of E1 genes, could replicate in and cause selective lysis of cancer cells. Mixed lymphocyte-tumor cell culture demonstrated that OBP-301-infected cancer cells stimulated PBMC to produce IFN-gamma into the supernatants. When the supernatants were subjected to the assay of in vitro angiogenesis, the tube formation of HUVECs was inhibited more efficiently than recombinant IFN-gamma. Moreover, in vivo angiogenic assay using a membrane-diffusion chamber system s.c. transplanted in nu/nu mice showed that tumor cell-induced neovascularization was markedly reduced when the chambers contained the mixed lymphocyte-tumor cell culture supernatants. The growth of s.c. murine colon tumors in syngenic mice was significantly inhibited due to the reduced vascularity by intratumoral injection of OBP-301. The antitumor as well as antiangiogenic effects, however, were less apparent in SCID mice due to the lack of host immune responses. Our data suggest that OBP-301 seems to have antiangiogenic properties through the stimulation of host immune cells to produce endogenous antiangiogenic factors such as IFN-gamma.


Pneumosinus dilatans and multiplex: report of three rare cases and review of the literature.
Pneumosinus dilatans is a term used to describe a localized abnormal dilatation of one or more paranasal sinuses without radiological evidence of localized bone destruction, hyperostosis or mucous membrane thickening. The involvement of all paranasal sinuses and mastoid air cells has been named pneumosinus dilatans multiplex. Although the involvement of one or more paranasal sinuses has been reported widely, all paranasal sinuses and the concomitant involvement of mastoid air cells has been reported in only one case. Herein, we present three unusual cases of pneumosinus dilatans (one is a second case of pneumosinus dilatans multiplex in English literature, another is the first reported case of a frontal pneumosinus dilatans case associated with frontoethmoidal meningocele, mental retardation and facial asymmetry and the third one is pneumosinus dilatans with a huge arachnoid cyst) along with the review of relevant literature.


Chirality meets visible-light photocatalysis in a molecular cerium vanadium oxide cluster.
The first example of a molecular cerium vanadium oxide photocatalyst is presented. A cerium vanadium oxide cluster, (nBu4N)2[(Ce(dmso)3)2V(IV)V(V)11O33Cl] × 2DMSO (1), was obtained by bottom-up self-assembly. The compound exhibits high visible-light photooxidative activity towards indigo with quantum efficiencies >10%. Initial mechanistic studies of the photooxidation reaction are presented. The structure of compound 1 is based on chiral, C2-symmetric cluster anions and both enantiomers are present in the crystal lattice. Retrosynthetic analysis suggests that chiral building blocks are spontaneously formed by symmetry breaking during self-assembly. The assembly of 1 based on the chiral building blocks is discussed conceptually. Consequences of this assembly mechanism for the development of chiral molecular catalysts and photocatalysts are described.


[New markers of cardio-renal links in chronic kidney disease].
To study the clinical significance of determining the serum concentration of phosphorus and calcium metabolism regulators--the morphogenetic proteins FGF-23 and Klotho in patients with different stages of chronic kidney disease (CKD). The serum levels of FGF-23 (a human FGF-23 ELISA kit with full-length anti-FCF-23 monoclonal antibodies) and Klotho (a human alpha-K1 ELISA with anti-Klotno antibodies) were investigated in 70 patients with Stages I--VD CKD (41 patients with chronic glomerulonephritis, including 10 with nephritis in systemic diseases, 22 with tubulointerstitial nephritis, and 7 with hypertensive nephroslerosis). The morphogenetic proteins were studied by the specialists of the LiTECH diagnostic laboratory according to the standard protocol. As CKD progressed from Stage I to VD, there were increased FGF-23 concentrations and decreased Klotho levels in the examinees' serum. The highest FGF-23 level and low Klotho concentration were noted in the group of patients on regular hemodialysis treatment (Stage VD). There was a strong inverse correlation between Klotho levels and proteinuria, C-reactive protein, and protein-energy insufficiency, which suggests that these factors influence the serum level of Klotho. The serum levels of FGF-23 and intact parathyroid hormone correlated with these values to a lesser degree. Analysis of the content of the morphogenetic proteins in patients with anemia versus those with CKD of the same stages and target hemoglobin values revealed low Klotho concentrations and high FGF-23 levels (r = 0.602; p < 0.01 and r = -0.450; p < 0.01, respectively). Forty-nine hypertensive patients showed a direct strong relationship between elevated serum FGF-23 levels and an inverse strong one between the reduced serum Klotho levels and the increased posterior left ventricular wall (r = 0.552; p < 0.01 and r = -0,587; p < 0.01, respectively). The same strong association was found between the higher serum level of FCF-23 (r = 0.492; p < 0.01) and the concentration of Klotho (r = -0.537; p < 0.01) and peripheral vascular resistance index (as evidenced by Doppler ultrasound study). Along with the active participation of the morphogenetic proteins (FGF-23 and Klotho) in mineral metabolism and its disturbances in CKD, their role is apparent in the development of cardiovascular events (in particular, through the involvement in the processes of vascular calcification and cardiac remodeling), anemia (through the possible effect on iron metabolism, enhanced ischemia of renal interstitial tissue with impaired Klotho production), and protein-energy insufficiency (through the participation in the processes of inflammation, oxidative stress, and protein synthesis).


Multivariate dynamical modelling of structural change during development.
Here we introduce a multivariate framework for characterising longitudinal changes in structural MRI using dynamical systems. The general approach enables modelling changes of states in multiple imaging biomarkers typically observed during brain development, plasticity, ageing and degeneration, e.g. regional gray matter volume of multiple regions of interest (ROIs). Structural brain states follow intrinsic dynamics according to a linear system with additional inputs accounting for potential driving forces of brain development. In particular, the inputs to the system are specified to account for known or latent developmental growth/decline factors, e.g. due to effects of growth hormones, puberty, or sudden behavioural changes etc. Because effects of developmental factors might be region-specific, the sensitivity of each ROI to contributions of each factor is explicitly modelled. In addition to the external effects of developmental factors on regional change, the framework enables modelling and inference about directed (potentially reciprocal) interactions between brain regions, due to competition for space, or structural connectivity, and suchlike. This approach accounts for repeated measures in typical MRI studies of development and aging. Model inversion and posterior distributions are obtained using earlier established variational methods enabling Bayesian evidence-based comparisons between various models of structural change. Using this approach we demonstrate dynamic cortical changes during brain maturation between 6 and 22 years of age using a large openly available longitudinal paediatric dataset with 637 scans from 289 individuals. In particular, we model volumetric changes in 26 bilateral ROIs, which cover large portions of cortical and subcortical gray matter. We account for (1) puberty-related effects on gray matter regions; (2) effects of an early transient growth process with additional time-lag parameter; (3) sexual dimorphism by modelling parameter differences between boys and girls. There is evidence that the regional pattern of sensitivity to dynamic hidden growth factors in late childhood is similar across genders and shows a consistent anterior-posterior gradient with strongest impact to prefrontal cortex (PFC) brain changes. Finally, we demonstrate the potential of the framework to explore the coupling of structural changes across a priori defined subnetworks using an example of previously established resting state functional connectivity.


CRYSTALLINE HUMAN UROKINASE: SOME PROPERTIES.
Human urokinase, an enzyme which activates plasminogen, has been crystallized. Repeated recrystallization yielded preparations of maximum specific activity; such preparations revealed only one component when subjected to polyacrylamide gel disc electrophoresis. Studies with the ultracentrifuge demonstrated that urokinase undergoes a concentration-dependent reversible association at pH 6.8. When the partial specific volume of the enzyme is assumed to be 0.735 milliliters per gram at 10 degrees C, Archibald measurements indicate the molecular weight of urokinase to be 53,000.


Model testing for reliability and validity of the Outcome Expectations for Exercise Scale.
Development of a reliable and valid measure of outcome expectations for exercise appropriate for older adults will help establish the relationship between outcome expectations and exercise. Once established, this measure can be used to facilitate the development of interventions to strengthen outcome expectations and improve adherence to regular exercise in older adults. Building on initial psychometrics of the Outcome Expectation for Exercise (OEE) Scale, the purpose of the current study was to use structural equation modeling to provide additional support for the reliability and validity of this measure. The OEE scale is a 9-item measure specifically focusing on the perceived consequences of exercise for older adults. The OEE scale was given to 191 residents in a continuing care retirement community. The mean age of the participants was 85 +/- 6.1 and the majority were female (76%), White (99%), and unmarried (76%). Using structural equation modeling, reliability was based on R2 values, and validity was based on a confirmatory factor analysis and path coefficients. There was continued evidence for reliability of the OEE based on R2 values ranging from .42 to .77, and validity with path coefficients ranging from .69 to .87, and evidence of model fit (X2 of 69, df = 27, p < .05, NFI = .98, RMSEA = .07). The evidence of reliability and validity of this measure has important implications for clinical work and research. The OEE scale can be used to identify older adults who have low outcome expectations for exercise, and interventions can then be implemented to strengthen these expectations and thereby improve exercise behavior.


Clustered DNA lesions containing 5-formyluracil and AP site: repair via the BER system.
Lesions in the DNA arise under ionizing irradiation conditions or various chemical oxidants as a single damage or as part of a multiply damaged site within 1-2 helical turns (clustered lesion). Here, we explored the repair opportunity of the apurinic/apyrimidinic site (AP site) composed of the clustered lesion with 5-formyluracil (5-foU) by the base excision repair (BER) proteins. We found, that if the AP site is shifted relative to the 5-foU of the opposite strand, it could be repaired primarily via the short-patch BER pathway. In this case, the cleavage efficiency of the AP site-containing DNA strand catalyzed by human apurinic/apyrimidinic endonuclease 1 (hAPE1) decreased under AP site excursion to the 3'-side relative to the lesion in the other DNA strand. DNA synthesis catalyzed by DNA polymerase lambda was more accurate in comparison to the one catalyzed by DNA polymerase beta. If the AP site was located exactly opposite 5-foU it was expected to switch the repair to the long-patch BER pathway. In this situation, human processivity factor hPCNA stimulates the process.


Current multiple myeloma treatment strategies with novel agents: a European perspective.
The treatment of multiple myeloma (MM) has undergone significant developments in recent years. The availability of the novel agents thalidomide, bortezomib, and lenalidomide has expanded treatment options and has improved the outcome of patients with MM. Following the introduction of these agents in the relapsed/refractory setting, they are also undergoing investigation in the initial treatment of MM. A number of phase III trials have demonstrated the efficacy of novel agent combinations in the transplant and nontransplant settings, and based on these results standard induction regimens are being challenged and replaced. In the transplant setting, a number of newer induction regimens are now available that have been shown to be superior to the vincristine, doxorubicin, and dexamethasone regimen. Similarly, in the front-line treatment of patients not eligible for transplantation, regimens incorporating novel agents have been found to be superior to the traditional melphalan plus prednisone regimen. Importantly, some of the novel agents appear to be active in patients with high-risk disease, such as adverse cytogenetic features, and certain comorbidities, such as renal impairment. This review presents an overview of the most recent data with these novel agents and summarizes European treatment practices incorporating the novel agents.


Cefpodoxime vs ciprofloxacin for short-course treatment of acute uncomplicated cystitis: a randomized trial.
Although fluoroquinolones remain the most reliable urinary antimicrobial, resistance rates have increased and effective fluoroquinolone-sparing antimicrobials are needed. To determine whether cefpodoxime is noninferior to ciprofloxacin for treatment of acute cystitis. Randomized, double-blind trial of 300 women aged 18 to 55 years with acute uncomplicated cystitis comparing ciprofloxacin (n = 150) with cefpodoxime (n = 150); patients were from a student health center in Seattle, Washington, and a referral center in Miami, Florida. The study was conducted from 2005 to 2009 and outcomes were assessed at 5 to 9 days and 28 to 30 days after completion of therapy. Intent-to-treat and per-protocol analyses were performed; 15 women in the ciprofloxacin group and 17 women in the cefpodoxime group were lost to follow-up. Patients were given 250 mg of ciprofloxacin orally twice daily for 3 days or 100 mg of cefpodoxime proxetil orally twice daily for 3 days. Overall clinical cure (defined as not requiring antimicrobial treatment during follow-up) at the 30-day follow-up visit. Secondary outcomes were clinical and microbiological cure at the first follow-up visit and vaginal Escherichia coli colonization at each follow-up visit. The hypothesis that cefpodoxime would be noninferior to ciprofloxacin by a 10% margin (ie, for the difference in the primary outcome for ciprofloxacin minus cefpodoxime, the upper limit of the confidence interval would be <10%) was formulated prior to data collection. The overall clinical cure rate at the 30-day visit with the intent-to-treat approach in which patients lost to follow-up were considered as having clinical cure was 93% (139/150) for ciprofloxacin compared with 82% (123/150) for cefpodoxime (difference of 11%; 95% CI, 3%-18%); and for the intent-to-treat approach in which patients lost to follow-up were considered as having not responded to treatment, the clinical cure rate was 83% (124/150) for ciprofloxacin compared with 71% (106/150) for cefpodoxime (difference of 12%; 95% CI, 3%-21%). The microbiological cure rate was 96% (123/128) for ciprofloxacin compared with 81% (104/129) for cefpodoxime (difference of 15%; 95% CI, 8%-23%). At first follow-up, 16% of women in the ciprofloxacin group compared with 40% of women in the cefpodoxime group had vaginal E coli colonization. Among women with uncomplicated cystitis, a 3-day regimen of cefpodoxime compared with ciprofloxacin did not meet criteria for noninferiority for achieving clinical cure. These findings, along with concerns about possible adverse ecological effects associated with other broad-spectrum β-lactams, do not support the use of cefpodoxime as a first-line fluoroquinolone-sparing antimicrobial for acute uncomplicated cystitis. clinicaltrials.gov Identifier: NCT00194532.


Evolution of a maternal immune activation (mIA) model in rats: Early developmental effects.
Maternal immune activation (mIA) in rodents is rapidly emerging as a key model for neurodevelopmental disorders such as autism spectrum disorder (ASD) and schizophrenia. Here, we optimise a mIA model in rats, aiming to address certain limitations of current work in this field. Specifically, the lack of clear evidence for methodology chosen, identification of successful induction of mIA in the dams and investigation of male offspring only. We focus on gestational and early juvenile changes in offspring following mIA, as detailed information on these critical early developmental time points is sparse. Following strain (Wistar, Lister Hooded, Sprague Dawley) comparison and selection, and polyriboinosinic-polyribocytidylic acid (poly I:C) dose selection (2.5-15 mg/kg single or once daily for 5 days), mIA was induced in pregnant Wistar rats with 10 mg/kg poly I:C i.p. on gestational day (GD) 15. Early morphometric analysis was conducted in male and female offspring at GD21 and postnatal day (PD) 21, eight dams for each treatment at each time point were used, 32 in total. Subsequent microglia analysis was conducted at PD21 in a small group of offspring. Poly I:C at 10 mg/kg i.p. induced a robust, but variable, plasma IL-6 response 3 h post-injection and reduced body weight at 6 h and 24 h post-injection in two separate cohorts of Wistar rats at GD15. Plasma IL-6 was not elevated at PD21 in offspring or dams. Poly I:C-induced mIA did not affect litter numbers, but resulted in PD21 pup, and GD21 placenta growth restriction. Poly I:C significantly increased microglial activation at PD21 in male hippocampi. We have identified 10 mg/kg poly I:C i.p on GD15 as a robust experimental approach for inducing mIA in Wistar rats and used this to identify early neurodevelopmental changes. This work provides a framework to study the developmental trajectory of disease-relevant, sex-specific phenotypic changes in rats.


Complete Genome Sequences of the Arcobacter cryaerophilus Strains ATCC 43158T and ATCC 49615.
Arcobacter cryaerophilus was originally recovered from aborted bovine and porcine fetuses, but it has been subsequently isolated from meat, water, and human clinical samples. This study describes the complete whole-genome sequences of two A. cryaerophilus strains, ATCC 43158T (=A 169/BT =LMG 24291T) and ATCC 49615 (=CDC D2610 =LMG 10829).


Reasons underpinning patients' preferences for various angina treatments.
To elicit patients' preferences for the treatment of angina. Angina patients were interviewed in order to elicit their personal reasons underlying preferences for various treatment options. Interviews followed a general repertory grid technique, in which seven treatment options were presented to patients in triads. Treatments considered ranged from medication to invasive revascularization therapies, with a 'no treatment' option. Two general practices in Norwich, Norfolk. Twenty-one patients with diagnosed angina, which was both mild and stable. Treatment preferences verbalized by patients during interview, and the underlying reasons for these. Attitudes voiced towards the range of treatments for angina were diverse; 27 different reasons underlying patients' preferences were identified. Patients' preferences were largely justified by reasons associated with the conditional effectiveness or otherwise of treatments. When presented with treatment triads, medication (drug) treatments were over 2.5 times more likely to be chosen as a most preferred option than invasive or surgical treatments. Although surgical treatments were generally considered to be 'effective', it was perceived that they were more appropriate for situations when the condition became life-threatening. There were occasions, however, when preferences were driven by other reasons, such as a desire to avoid surgery because it was perceived negatively as 'invasive' and 'frightening'. Drug treatments were viewed as 'quick', 'easy' and reversible. Personal experiences of the effectiveness or otherwise of treatments were frequently cited as reasons for stated preferences. However, patients often commented that they would prefer the doctor to make the decision about their treatment. Patients choices among treatments was largely driven by perceptions of their effectiveness or otherwise. Although surgery was perceived as 'effective' it was also seen as conditionally so, dependent upon severity of the condition - which is not necessarily the case, as the risks of adverse events and surgical complications increase for emergency cases. As such, access to better information about the effectiveness and timeliness of interventions is needed. Although respondents held anxieties about treatment, particularly invasive or surgical treatments, fewer choices were driven by emotional and lifestyle factors unrelated to 'effectiveness', such as fear or ease of treatment.


Neural substrates for the effects of rehabilitative training on motor recovery after ischemic infarct.
Substantial functional reorganization takes place in the motor cortex of adult primates after a focal ischemic infarct, as might occur in stroke. A subtotal lesion confined to a small portion of the representation of one hand was previously shown to result in a further loss of hand territory in the adjacent, undamaged cortex of adult squirrel monkeys. In the present study, retraining of skilled hand use after similar infarcts resulted in prevention of the loss of hand territory adjacent to the infarct. In some instances, the hand representations expanded into regions formerly occupied by representations of the elbow and shoulder. Functional reorganization in the undamaged motor cortex was accompanied by behavioral recovery of skilled hand function. These results suggest that, after local damage to the motor cortex, rehabilitative training can shape subsequent reorganization in the adjacent intact cortex, and that the undamaged motor cortex may play an important role in motor recovery.


Emergence of exploratory look-around behaviors through active observation completion.
Standard computer vision systems assume access to intelligently captured inputs (e.g., photos from a human photographer), yet autonomously capturing good observations is a major challenge in itself. We address the problem of learning to look around: How can an agent learn to acquire informative visual observations? We propose a reinforcement learning solution, where the agent is rewarded for reducing its uncertainty about the unobserved portions of its environment. Specifically, the agent is trained to select a short sequence of glimpses, after which it must infer the appearance of its full environment. To address the challenge of sparse rewards, we further introduce sidekick policy learning, which exploits the asymmetry in observability between training and test time. The proposed methods learned observation policies that not only performed the completion task for which they were trained but also generalized to exhibit useful "look-around" behavior for a range of active perception tasks.


Continuous transformation learning of translation invariant representations.
We show that spatial continuity can enable a network to learn translation invariant representations of objects by self-organization in a hierarchical model of cortical processing in the ventral visual system. During 'continuous transformation learning', the active synapses from each overlapping transform are associatively modified onto the set of postsynaptic neurons. Because other transforms of the same object overlap with previously learned exemplars, a common set of postsynaptic neurons is activated by the new transforms, and learning of the new active inputs onto the same postsynaptic neurons is facilitated. We show that the transforms must be close for this to occur; that the temporal order of presentation of each transformed image during training is not crucial for learning to occur; that relatively large numbers of transforms can be learned; and that such continuous transformation learning can be usefully combined with temporal trace training.


Hypoxia-induced gene expression in chemoradioresistant cervical cancer revealed by dynamic contrast-enhanced MRI.
Knowledge of the molecular background of functional magnetic resonance (MR) images is required to fully exploit their potential in cancer management. We explored the prognostic impact of dynamic contrast-enhanced MR imaging (DCE-MRI) parameters in cervical cancer combined with global gene expression data to reveal their underlying molecular phenotype and construct a representative gene signature for the relevant parameter. On the basis of 78 patients with cervical cancer subjected to curative chemoradiotherapy, we identified the prognostic DCE-MRI parameter A(Brix) by pharmacokinetic analysis of pretreatment images based on the Brix model, in which tumors with low A(Brix) appeared to be most aggressive. Gene set analysis of 46 tumors with pairwise DCE-MRI and gene expression data showed a significant correlation between A(Brix) and the hypoxia gene sets, whereas gene sets related to other tumor phenotypes were not significant. Hypoxia gene sets specific for cervical cancer created in cell culture experiments, including both targets of the hypoxia inducible factor (HIF1α) and the unfolded protein response, were the most significant. In the remaining 32 tumors, low A(Brix) was associated with upregulation of HIF1α protein expression, as assessed by immunohistochemistry, consistent with increased hypoxia. On the basis of the hypoxia gene sets, a signature of 31 genes that were upregulated in tumors with low A(Brix) was constructed. This DCE-MRI hypoxia gene signature showed prognostic impact in an independent validation cohort of 109 patients. Our findings reveal the molecular basis of an aggressive hypoxic phenotype and suggest the use of DCE-MRI to noninvasively identify patients with hypoxia-related chemoradioresistance.


Real-time elastosonography of lipomatous vs. malignant subcutaneous neoplasms in dogs: Preliminary results.
Real-time elastography is a recently introduced ultrasound technique allowing the investigation of elastic properties of tissues. A diagnostic accuracy study was conducted to test the performance of this technique in the assessment of subcutaneous lesions in dogs. Fifty-two dogs were prospectively included in the preliminary study (34 malignant and 18 benign lesions). B-mode ultrasound was performed assessing the shape, margins, heterogeneity, and echotexture of the lesions. On elastosonography, assessment of the percentage of softness/hardness was recorded. A qualitative assessment was performed according to the Tsukuba elasticity score with a 1-5 score, representing the increased percentage of high stiffness areas. Results were compared with cytology/histopathology of the lesions. Receiver Operating Curves of the overall diagnostic sensitivity and specificity were obtained. Fisher's exact test and Pearsons's Chi-squared test estimated the relationship between the B-mode appearance of the lesions and final diagnosis. A hardness cutoff of 50.25% was identified between lesions, with malignant neoplasms having higher percentages. A 100% specificity and 89% sensitivity for correctly detecting the nature of the lesion on elastosonography was established. Qualitative assessment of the Tsukuba elasticity score established 1.5 as the cutoff between elastograms of lipomatous and malignant lesions, with 100% sensitivity and 61% specificity in differentiating them. Real-time elastosonography is a novel, noninvasive, and accurate technique for differentiating malignant from benign lipomatous lesions in dogs. This method could be considered as a complementary tool with additional diagnostic value for routine invasive procedures, such as fine needle aspirates.


Self-disorders in Early Stages of the Schizophrenia Spectrum.
The pathogenic nucleus of schizophrenia has varied according to the different eras and influences of distinguished clinical researchers. Self-disorders have also been recognised to be at the heart of this disorder, although they have seldom been studied due to their subjective nature. Recently, due to the growing interest in the study of the early stages of schizophrenia, the study of self-disorders has been resumed. The self-disorders in schizophrenia model, developed by Sass and Parnas, proposes that in this disorder the person suffers loss of the first-person perspective and experiences hyperreflexibility, diminished self-affection and disturbance of the field of awareness. Therefore, the person experiences feelings of strangeness about him/herself, difficulty in understanding the common sense of things and difficulty interacting with his/her environment. Based on this model, self-disorder evaluation instruments have been developed and empirical studies have been conducted to evaluate people at risk of developing a schizophrenia spectrum disorder. These studies show that self-disorders are found in prepsychotic stages and that their manifestation may predict the transition to schizophrenia spectrum disorders. These results have important clinical implications as they enable people in the early stages of the disorder to be identified and create the opportunity to apply early therapeutic interventions.


Mechanistic link between lidocaine block and inactivation probed by outer pore mutations in the rat micro1 skeletal muscle sodium channel.
1. Mutations that disrupt Na+ channel fast inactivation attenuate lidocaine (lignocaine)-induced use dependence; however, the pharmacological role of slower inactivation processes remains unclear. In Xenopus oocytes, tryptophan substitution in the outer pore of the rat skeletal muscle channel (micro1-W402) alters partitioning among fast- and slow-inactivated states. We therefore examined the effects of W402 mutations on lidocaine block. 2. Recovery from inactivation exhibited three kinetic components (IF, fast; IM, intermediate; IS, slow). The effects of W402A and W402S on IF and IS differed, but both mutants (with or without beta1 subunit coexpression) decreased the amplitude of IM. In wild-type channels, lidocaine imposed a delayed recovery component with intermediate kinetics, and use-dependent block was attenuated in both W402A and W402S. 3. To examine the pharmacological role of IS relative to IM, drug-exposed beta1-coexpressed channels were subjected to 2 min depolarizations. Lidocaine had no effect on sodium current (INa) after a 1 s hyperpolarization interval that allowed recovery from IM but not IS, suggesting that lidocaine affinity for IS is low. 4. Both W402 mutations reduced occupancy of IM in drug-free conditions, and also induced resistance to use-dependent block. We propose that lidocaine-induced use dependence may involve an allosteric conformational change in the outer pore.


Effect of zirconia surface treatments on the shear strength of zirconia/veneering ceramic composites.
Aim of the investigation was to assess the effect of different surface treatments on the bond strength of veneering ceramics to zirconia. In a shear test, the influences of polishing, sandblasting, and silica-coating of the zirconia surface on bonding were assessed with five different veneering ceramics. In addition the effect of liner application was examined. With one veneering ceramic, the impact of regeneration firing of zirconia was also evaluated. Statistical analysis was performed with one-way ANOVA and post hoc Scheffé's test. Failure in every case occurred in the veneering ceramic adjacent to the interface with a thin layer of ceramic remaining on the zirconia surface, indicating that bond strength was higher than the cohesive strength of the veneering ceramic. Shear strength ranged from 23.5 +/- 3.4 MPa to 33.0 +/- 6.8 MPa without explicit correlation to the respective surface treatment. Regeneration firing significantly decreased the shear strength of both polished and sandblasted surfaces. Findings of this study revealed that bonding between veneering ceramics and zirconia might be based on chemical bonds. On this note, sandblasting was not a necessary surface pretreatment to enhance bond strength and that regeneration firing was not recommended.


Evaluation of cerebral blood flow data in stroke patients using a mapping system.
We retrospectively examined regional cerebral blood flow values in 78 patients in the stabilized phase of stroke to evaluate the consistency of lateralization compared with computed tomographic imaging. Examinations were performed using the xenon-133 inhalation technique, and the data were processed and displayed by a computer-assisted system of our own design that allows statistical analysis in real time and is suitable for clinical use. The consistency of lateralization correlated with computed tomographic findings was tested for absolute values, percent distribution, and asymmetries. The latter yielded the highest degree of sensitivity (in 83.3% of the patients the affected hemisphere was correctly identified). Absolute values showed at least one hypoperfused area in the affected hemisphere in 48.7% of the patients, and percent distribution did so in 57.7%. Furthermore, the combination of the three methods of data analysis yielded a sensitivity of 91%; the remaining 9% of the patients, however, exhibited some abnormalities of regional cerebral blood flow (bilateral or contralateral hypoperfusion). Although good agreement was found for lateralization by computed tomography and by the combined use of the three methods of analysis, a complete overlap between functional and structural examinations should not be expected. Problems concerning the sensitivity of the xenon-133 inhalation technique under conditions of low blood flow and the statistical analysis of regional cerebral blood flow data are discussed.


Discordance between living and death assemblages as evidence for anthropogenic ecological change.
Mismatches between the composition of a time-averaged death assemblage (dead remains sieved from the upper mixed-zone of the sedimentary column) and the local living community are typically attributed to natural postmortem processes. However, statistical analysis of 73 molluscan data sets from estuaries and lagoons reveals significantly poorer average "live-dead agreement" in settings of documented anthropogenic eutrophication (AE) than in areas where AE and other human impacts are negligible. Taxonomic similarity of paired live and dead species lists declines steadily among areas as a function of AE severity, and, for data sets comprising only adults, rank-order agreement in species abundance drops where AE is suspected. The observed live-dead differences in composition are consistent with eutrophication (anomalous abundance of seagrass-dwellers and/or scarcity of organic-loving species in the death assemblage), suggesting compositional inertia of death assemblages to recent environmental change. Molluscan data sets from open shelf settings (n = 34) also show higher average live-dead discordance in areas of AE. These results indicate that (i) live-dead discordance in surficial grab samples provides valuable evidence for strong anthropogenic modification of benthic communities, (ii) actualistic estimates of the ecological fidelity of molluscan death assemblages tend to be erroneously pessimistic when conducted in nonpristine settings, and (iii) based on their high fidelity in pristine study areas, death assemblages are a promising means of reconstructing otherwise elusive preimpact ecological baselines from sedimentary records.


Metastasis of mesothelioma to the maxillary gingiva.
Malignant mesothelioma predominantly arises from the serosal surfaces of the pleural or peritoneal cavity. There is currently no effective standard treatment for mesothelioma and the prognosis for patients is poor; the majority of patients with malignant mesothelioma succumb between 12 and 17 months following diagnosis. The association of all forms of malignant mesothelioma with asbestos exposure has been well documented. However, metastasis to the oral gingiva is rare, as only four cases have previously been reported; two cases of metastasis to the tongue and four cases to the jaw bone. In the current report, the case of a 62-year-old male with metastatic mesothelioma is presented. To the best of our knowledge, this is the first report regarding the metastasis of this type of neoplasm to the maxillary gingiva.


Protection of rat chromosomes by melatonin against gamma radiation-induced damage.
The aim of this study was to investigate the protective effect of melatonin (2.5mg/kg/day, given to rats five times by intra-peritoneal injection) against damage in bone-marrow chromosomes induced by a single dose of gamma radiation (4.0 Gy whole-body irradiation; WBI). Ninety-six male albino rats were divided into four equal groups of 24 rats each. They were designated as I-non-irradiated, non-treated control rats, II-non-irradiated rats treated with melatonin for five successive days, III-whole-body gamma-irradiated rats and IV-rats injected with melatonin daily for five successive days, then subjected to whole-body gamma irradiation 2h after the final melatonin injection. Six rats from each group were sacrificed at days 1, 3, 7 and 10 following treatment and/or irradiation and their bone marrows were flushed out for micronuclei scoring and chromosomal analysis. WBI resulted in significant elevations in bone-marrow polychromatic erythrocytes containing micronuclei in their cytoplasm, and caused a significant decrease in the mitotic index of bone-marrow cells; in addition, there was a significant increase in the frequency of aberrant bone-marrow cells and in the different types of structural chromosomal aberration. Melatonin injection prior to WBI significantly reduced the mean frequencies of micro-nucleated polychromatic erythrocytes and of aberrant cells, as well as the incidence of structural chromosomal aberrations in bone-marrow cells; it also caused a highly significant elevation in the value of the mitotic index of bone-marrow cells. This investigation clarifies the protective and/or ameliorative role played by melatonin against deleterious effects of gamma radiation.


Effects of active on-call hours on physicians' turnover intentions and well-being.
This study examined whether active on-call hours and the co-occurrence of lifestyle risk factors are associated with physicians' turnover intentions and distress. Cross-sectional survey data on randomly selected female (N=1571) and male (N=1081) physicians, aged 25 to 65 years, from The Finnish Health Care Professionals Study were used. The outcome measures were turnover intentions and distress (general health questionnaire). Smoking, heavy drinking, overweight, and low physical activity were assessed as lifestyle risk factors. Analyses of covariance were used to analyze the data. After adjustment for gender, age, employment sector, and job satisfaction, the analyses showed that the physicians who had been on active call more than 40 hours per month reported more distress than the group not on call (P=0.046). The physicians with two or more risk factors also had more distress (P<0.001) than those with no risk factors or only one risk factor. There was an interaction between active on-call hours and lifestyle risk factors for turnover intentions (P=0.002). The physicians with two or more lifestyle risk factors who had been on active call more than 40 hours per month had more turnover intentions than the other physicians. On-call duty and the co-occurrence of lifestyle risk factors may both decrease physicians' well being and increase their intentions to leave their job.


Viewpoint: Economic evaluation of package of care interventions employing clinical guidelines.
Increasingly attention is shifting towards delivering essential packages of care, often based on clinical practice guidelines, as a means to improve maternal, child and newborn survival in low-income settings. Cost effectiveness analysis (CEA), allied to the evaluation of less complex intervention, has become an increasingly important tool for priority setting. Arguably such analyses should be extended to inform decisions around the deployment of more complex interventions. In the discussion, we illustrate some of the challenges facing the extension of CEA to this area. We suggest that there are both practical and methodological challenges to overcome when conducting economic evaluation for packages of care interventions that incorporate clinical guidelines. Some might be overcome by developing specific guidance on approaches, for example clarity in identifying relevant costs. Some require consensus on methods. The greatest challenge, however, lies in how to incorporate, as measures of effectiveness, process measures of service quality. Questions on which measures to use, how multiple measures might be combined, how improvements in one area might be compared with those in another and what value is associated with improvement in health worker practices are yet to be answered.


Prevalence and correlates of lower extremity arterial disease in elderly women.
Although lower extremity arterial disease occurs in 15-20% of the population over the age of 75 years, little is known about the etiology of the disease in women. In this cross-sectional study involving 1,601 healthy elderly women (mean age, 71 years; range, 65-93 years), the occurrence of lower extremity arterial disease was assessed noninvasively by measuring brachial and ankle pressures bilaterally. Disease prevalence ranged from 2.9% in those aged 65-69 years to 15.5% in those aged 80 years or older. Approximately 20% of those with disease had symptoms of claudication. Age, systolic blood pressure, and current smoking status were strong independent risk factors for arterial disease; a history of arthritis, use of nonthiazide diuretics, current coffee drinking, and upper body obesity were also independent correlates. The number of pack-years in current and former smokers and the number of cigarettes per day used by current smokers showed a dose-response relation with disease. The population attributable risk for current smoking was 26%. The major correlates for symptomatic arterial disease were current smoking and systolic blood pressure. It is concluded that the major risk factors for lower extremity arterial disease in elderly women are similar to those in men. Preventive efforts should focus on smoking cessation and management of hypertension.


Persecutory delusions: developing the understanding of belief maintenance and emotional distress.
The objective of the study was to develop the cognitive understanding of persecutory delusions. It was hypothesized that safety behaviours contribute to the persistence of persecutory delusions by preventing disconfirmation. It was further hypothesized that emotional distress is associated with aspects of the content of delusions. An investigation was designed to establish whether individuals with persecutory delusions use safety behaviours, and to test predicted associations between delusion content and emotional distress. A cross-sectional investigation was conducted on 25 individuals with persecutory delusions. A detailed assessment was made of the presence of safety behaviours, the content of delusions and emotional distress. All participants had used at least one safety behaviour in the last month, most typically avoidance. Higher levels of anxiety were associated with greater use of safety behaviours. New data were obtained on the content of persecutory delusions. Aspects of the content of the delusions were associated with levels of depression, self-esteem, anxiety and delusional distress. Individuals with persecutory delusions use safety behaviours. The findings may develop the understanding of delusion persistence, acting upon delusions and the negative symptoms of schizophrenia. There are implications for cognitive interventions for psychosis. Support was also found for the hypothesis that emotional distress is linked to the content of delusional beliefs; it is speculated that prior emotional distress influences the content of delusions, and that delusion content in turn influences levels of emotional distress.


The effects of unilateral forced nostril breathing on cognitive performance.
This study describes the effects of 30 minutes of unilateral forced nostril breathing on cognitive performance in 51 right-handed undergraduate psychology students (25 males and 26 females). A verbal analogies task modeled after the Miller Analogies and SAT Tests was used as a test of left-hemispheric performance and mental rotation tasks based on the Vandenburg and Kuse adaptation of Shepard and Metzler's tests were used as spatial tasks for testing right-hemispheric performance. Spatial task performance was significantly enhanced during left nostril breathing in both males and females, p = .028. Verbal task performance was greater during right nostril breathing, but not significantly p = .14. These results are discussed in comparison to other cognitive and physiological studies using unilateral forced nostril breathing. This yogic breathing technique may have useful application in treating psychophysiological disorders with hemispheric imbalances and disorders with autonomic abnormalities.


Identification of two homologs of the Kaposi's sarcoma-associated herpesvirus (human herpesvirus 8) in retroperitoneal fibromatosis of different macaque species.
Simian retroperitoneal fibromatosis (RF) is a vascular fibroproliferative neoplasm which has many morphological and histological similarities to human Kaposi's sarcoma (KS). Like epidemic KS in AIDS patients, RF is highly associated with an immunodeficiency syndrome (simian acquired immunodeficiency syndrome [SAIDS]) caused by a retrovirus infection. Recently, a new gammaherpesvirus, called Kaposi's sarcoma-associated herpesvirus (KSHV) or human herpesvirus 8 (HHV8), has been identified in KS tumors, suggesting that KS has a viral etiology. Our previous experimental transmission studies and epidemiological data suggest that RF also has an infectious etiology. In order to determine whether a similar virus is also associated with RF, we have assayed for the presence of an unknown herpesvirus using degenerate PCR primers targeting the highly conserved DNA polymerase genes of the herpesvirus family. Here we provide DNA sequence evidence for two new herpesviruses closely related to KSHV from RF tissues of two macaque species, Macaca nemestrina and Macaca mulatta. Our data suggest that KSHV and the putative macaque herpesviruses define a new group within the subfamily Gammaherpesvirinae whose members are implicated in the pathogenesis of KS and KS-like neoplasms in different primate species.


Quality of life of patients with vitiligo attending the Regional Dermatology Training Center in Northern Tanzania.
Vitiligo is an acquired, predominantly asymptomatic, depigmenting disorder with profound psychological effects. This was a cross-sectional study conducted at the Regional Dermatology Training Center in Moshi, Tanzania. All 88 patients with vitiligo older than 15 years of age who attended the skin clinic from October 2009 to April 2010 were recruited. Data were collected using a structured questionnaire, Dermatology Life Quality Index questionnaire (DLQI), and Vitiligo European Task Force form. Vitiligo moderately affects patient's quality of life, as indicated by a DLQI mean score of 7.2 ± 4.8. The mean age was 41 years with a male/female ratio of 1:1.7. The mean age of disease onset was 33.5 years (range 16-83 years); vitiligo vulgaris was the most common disease form seen (n = 49). None of the factors considered were found to be significantly associated with impaired quality of life on multivariate analysis. The majority of patients (73.8%) perceived that their disease was moderate to severe in contrast to the clinical grading in which only 49.2% patients were classified as having mild disease. This difference in classification of disease severity was statistically significant (Fishers exact test = 0.001). Patients with vitiligo of African descent have a moderate impairment of quality of life.


Psychological stress induces sodium and fluid retention in men at high risk for hypertension.
Exposure to competitive mental tasks significantly reduced the urinary sodium and fluid excreted by young men with one or two hypertensive parents or with borderline hypertension. In this high-risk group, the degree of retention was directly related to the magnitude of heart rate increase during stress, suggesting common mediation by way of the sympathetic nervous system. Thus, psychological stress appears to induce changes in renal excretory functions that may play a critical role in long-term blood pressure regulation.


Mean reticolocyte hemoglobin content index plays a key role to identify children who are carriers of β-thalassemia.
Reticulocyte (r) and red blood cell (RBC) indices provide reliable parameters for screening and monitoring iron deficiency anemia (IDA) patients and β-thalassemia trait (BTT) carriers. The aim of this study is to identify a simple method for use to distinguish β-thalassemia trait carriers from IDA and to evaluate the correlation between BTT genetic mutation and MCV values and new discrimination index for the detection of β-thalassemia trait (DI-BTT). We analyzed CHr, MCHCr, MCVr, RBC, mean cellular hemoglobin concentration (MCHC) and mean cellular volume (MCV) indices among a pediatric population of IDA patients (n=90), β-thalassemia trait carriers (n=72) and normal controls (NC) (n=131). Furthermore, to distinguish IDA patients from β-thalassemia trait carriers we evaluated clinical utility of new DI for the detection BTTcarriers, using the following polynomial: (RBC × MCHC × 50/MCV)/CHr. We found that CHr, MCVr and DI-BTT mean values were significantly different between β-thalassemia trait carriers and IDA patients. CHr, MCVr and DI-BTT plotting curves showed exclusive distribution in β-thalassemia trait carriers. Moreover, DI-BTT was very accurate in differentiating β-thalassemia trait carriers from IDA patients. All BTT patients showed a heterozygous mutation of the β-globin gene including CD39, IVS1.110, IVS1.6 and IVS2.745, IVS2.1 and IVS1.1. The highest MCV values were displayed by those carrying the IVS1.6 mutation. The simultaneous measurement and plotting of CHr and MCVr indices, as well as the DI-BTT allow to distinguish β-thalassemia carriers from IDA patients.


The split flexor digitorum superficialis.
Variations of the muscles of the anterior forearm are common. We report the cadaveric findings of an unusual variant of flexor digitorum superficialis (FDS). The deep part of the FDS was found to be split and showed two distinct fusiform muscle bellies. The medial belly originated from the common flexor tendon from the medial condyle of the humerus and continued as a thin tendon at the middle of the forearm to insert onto the fifth digit. The lateral belly blended proximally with the deep surface of the superficial portion of the FDS and ended in a relatively thicker tendon, which was inserted onto the second digit. The median nerve passed between the medial and lateral bellies of the deep part of the FDS. To our knowledge, this is only the second report of a split FDS in the extant literature. A review of neuromuscular variations of the anterior forearm is presented.


Un-collimated single-photon imaging system for high-sensitivity small animal and plant imaging.
In preclinical single-photon emission computed tomography (SPECT) system development the primary objective has been to improve spatial resolution by using novel parallel-hole or multi-pinhole collimator geometries. However, such high-resolution systems have relatively poor sensitivity (typically 0.01-0.1%). In contrast, a system that does not use collimators can achieve very high-sensitivity. Here we present a high-sensitivity un-collimated detector single-photon imaging (UCD-SPI) system for the imaging of both small animals and plants. This scanner consists of two thin, closely spaced, pixelated scintillator detectors that use NaI(Tl), CsI(Na), or BGO. The performance of the system has been characterized by measuring sensitivity, spatial resolution, linearity, detection limits, and uniformity. With (99m)Tc (140 keV) at the center of the field of view (20 mm scintillator separation), the sensitivity was measured to be 31.8% using the NaI(Tl) detectors and 40.2% with CsI(Na). The best spatial resolution (FWHM when the image formed as the geometric mean of the two detector heads, 20 mm scintillator separation) was 19.0 mm for NaI(Tl) and 11.9 mm for CsI(Na) at 140 keV, and 19.5 mm for BGO at 1116 keV, which is somewhat degraded compared to the cm-scale resolution obtained with only one detector head and a close source. The quantitative accuracy of the system's linearity is better than 2% with detection down to activity levels of 100 nCi. Two in vivo animal studies (a renal scan using (99m)Tc MAG-3 and a thyroid scan with (123)I) and one plant study (a (99m)TcO4(-) xylem transport study) highlight the unique capabilities of this UCD-SPI system. From the renal scan, we observe approximately a one thousand-fold increase in sensitivity compared to the Siemens Inveon SPECT/CT scanner. UCD-SPI is useful for many imaging tasks that do not require excellent spatial resolution, such as high-throughput screening applications, simple radiotracer uptake studies in tumor xenografts, dynamic studies where very good temporal resolution is critical, or in planta imaging of radioisotopes at low concentrations.


Is it Time for Cementless Hip Resurfacing?
Metal-on-metal bearing with cemented femoral component and cementless acetabular fixation is the current standard in surface replacement arthroplasty (RSA) of the hip. Because of concerns about the long-term survivorship of cemented stems in conventional hip arthroplasty, it seems logical to achieve cementless fixation on the femoral side with RSA. The goals of this review were to evaluate clinical and radiological data reported from previously published cementless RSA series. In addition, we intend to review author's preliminary experience with Conserve Plus cementless devices specifically assessing the clinical outcomes, the complications rate, the survivorship, and the metallic ions levels measured in follow-up. A references search was done with PubMed using the key words "cementless hip resurfacing", "cementless hip resurfacing prosthesis", and "femoral cementless hip resurfacing". Additionally, the clinical outcomes, the complications rate, the survivorship, and the metallic ions levels were measured in 94 cementless Conserve Plus(©) devices in 90 patients (68 males and 22 females) with a mean age of 41.1 years (18-59). Mean follow-up was 13.1 months (8-16). No revision was performed during the observed follow-up. Neither radiological signs of loosening nor neck narrowing >10% were evident. Chromium and cobalt levels in whole blood samples rose respectively from 0.53 μg/l (0.1-1.7) to 1.7 μg/l (0.6-2.9) and from 0.54 μg/l (0.1-1.4) to 1.98 μg/l (0.1-2.8). Cementless "fit and fill" femoral-side fixation, which seems to be potentially evolved and design-related, should be considered for future hip-resurfacing device generations.