What makes specialized food-caching mountain chickadees successful city slickers?
Anthropogenic environments are a dominant feature of the modern world; therefore, understanding which traits allow animals to succeed in these urban environments is especially important. Overall, generalist species are thought to be most successful in urban environments, with better general cognition and less neophobia as suggested critical traits. It is less clear, however, which traits would be favoured in urban environments in highly specialized species. Here, we compared highly specialized food-caching mountain chickadees living in an urban environment (Reno, NV, USA) with those living in their natural environment to investigate what makes this species successful in the city. Using a 'common garden' paradigm, we found that urban mountain chickadees tended to explore a novel environment faster and moved more frequently, were better at novel problem-solving, had better long-term spatial memory retention and had a larger telencephalon volume compared with forest chickadees. There were no significant differences between urban and forest chickadees in neophobia, food-caching rates, spatial memory acquisition, hippocampus volume, or the total number of hippocampal neurons. Our results partially support the idea that some traits associated with behavioural flexibility and innovation are associated with successful establishment in urban environments, but differences in long-term spatial memory retention suggest that even this trait specialized for food-caching may be advantageous. Our results highlight the importance of environmental context, species biology, and temporal aspects of invasion in understanding how urban environments are associated with behavioural and cognitive phenotypes and suggest that there is likely no one suite of traits that makes urban animals successful.


Studying translational control in Drosophila cell-free systems.
Classically, Drosophila cell-free translation systems have been used to study the response of the translational machinery to heat shock treatment. We and others have developed optimized Drosophila embryo and ovary extracts, and their use has expanded to the study of a variety of translational control events. These extracts recapitulate many of the aspects of mRNA translation observed in vivo and retain critical regulatory features of several translational control processes. Indeed, their use is rapidly improving our knowledge of molecular mechanisms of translational control. In this chapter we provide general guidelines and detailed protocols to obtain and use translation extracts derived from Drosophila embryos and ovaries.


Chemical constituents of Silene montbretiana.
A new steroidal glycoside, 3- O-β-d-glucopyranosyl-3β,25-dihydroxy-5β-cholest-7-en-6-one 25- O-β-d-glucopyranoside (1), together with six known steroidal derivatives (2-7), one cerebroside (8) and one flavonoid (9) were isolated from Silene montbretiana Boiss (Caryophyllaceae), a perennial herb growing mainly in the Middle and East Anatolia, Azerbaijan, Iran, and Turkey. Their structures were established by the extensive use of 1D and 2D NMR experiments along with ESI-MS analyses. The cytotoxicity against the cancer A549 (human alveolar basal carcinoma) and Hela (human epitheloid cervix carcinoma) cell lines has been evaluated. None of the tested compounds, in a range of concentrations between 12.5 and 100 μM, caused a significant reduction of the cell number.


Mushroom poisoning: a case report from Jordan.
An eight years male child with his family ate fresh mushroom at lunch time from back garden at their home in a village in the North of Jordan. By the evening approximately six hours later all started feeling nausea, abdominal cramps and vomiting they rushed to nearest primary health care center. After getting general medical medication they were transfer to a referral hospital at city of Irbid. The boy got deteriorated with diarrhea in addition to the previous gastrointestinal complains and died on third day. The message from this case is to ascertain in the public opinion that unknown type of mushroom even eaten previously could be poisonous and fetal.


Correcting low vision in aphakic children.
There are many children who have subnormal vision in spite of successful cataract surgery and aphakic spectacle lenses. There are children who have lens opacities for whom the state of aphakia would not be an improvement. Careful evaluation of functional vision, careful refraction, and the prescription of high adds or other optical devices are part of complete ophthalmological care for every one of these children. The dioptric strength of the reading add is determined by the functional reading vision and the calculation of the reciprocal of the visual acuity. It is also important to realize that many children who have lens opacities do not require special aids; functional vision is adequate until their accommodative reserve wanes with age. Continuous-wear contact lenses may eventually replace spectacle corrections for the aphakic child.


Application of a Hybrid Model of Big Data and BP Network on Fault Diagnosis Strategy for Microgrid.
Aiming at the characteristics of timely transmission, rapid update, and large magnitude of microgrid data, based on the large data samples generated by microgrid operation, a fault diagnosis and analysis method of microgrid systems supported by big data is proposed in this paper. The multisource joint feature vectors of microgrid are extracted using Wavelet transform, Rayleigh entropy, and big data technology, which combine short-circuit current and voltage. The extracted feature dataset is clustered and segmented to realize deep data mining. Combining BP neural network and big data, the fault diagnosis of microgrid is realized. The simulation results show that the BP neural network algorithm based on big data support can accurately identify the type and phase of internal faults in microgrid, which is more suitable for extracting the temporal characteristics of information and spatiotemporal correlation of data to realize the prediction of big data and solve the core problems in the analysis of big data of microgrid faults, and the accuracy is as high as 96.8%.


Bone sporotrichosis: 41 cases from a reference hospital in Rio de Janeiro, Brazil.
Bone sporotrichosis is rare. The metropolitan region of Rio de Janeiro is hyperendemic for zoonotic sporotrichosis and the bone presentations are increasing. We studied a retrospective cohort of 41 cases of bone sporotrichosis, diagnosed from 1999-2016. The inclusion criteria was fungal culture isolation from any clinical specimen associated to bone involvement (radiography and/or computed tomography) compatible with fungal osteomyelitis or histopathological findings of bone material compatible with sporotrichosis. Molecular identification was performed when possible. Male patients represented 58.5% of the cases, with a cohort median age of 43 years. Immunosuppressive conditions were present in 68.3% of the patients, mostly HIV coinfection (51.2%). Multifocal bone involvement (more than one anatomical segment) was diagnosed in 61% of the patients, while 39% presented unifocal involvement. The bones of the hands were the most affected (58.5%), followed by the feet (41.5%) and tibia (26.8%). Multifocal group was characterized by a higher proportion of males (p = 0.0045) with immunosuppressive conditions (p = 0.0014). Amphotericin B followed by oral itraconazole was the main treatment, with a median time of 16.7 months (1.5 to 99.2 months), and cure of 53.7% of the patients (84.6% of immunocompetent and 39.3% of immunocompromised patients). Sequelae occurred in 12.2% of the patients-amputations (7.3%) and ankylosis (4.9%), while 22% died in the course of the disease. Sporothrix brasiliensis was the causative agent in all the 9 (22%) performed cases. Bone sporotrichosis is a chronic, challenging condition with prolonged treatment, often with poor results and sequelae.


[Application of Virtual Reality in a Super-Aging Society].
Generally, when the proportion of the population aged ≥65 years exceeds 21% of the total population, it is referred to as a "super-aging society." In 2022, Japan surpassed this ratio, reaching 29%, presenting a significant challenge in sustaining the generous government support being provided. Maintaining connections with the community as individuals age, amid changes in their lives, bodies, and social relationships, is also considered crucial for the physical and mental well-being. Virtual reality may emerge as a potentially valuable tool aiding the promotion of health and social engagement of older people.


Characteristics of Authigenic Minerals around the Sulfate-Methane Transition Zone in the Methane-Rich Sediments of the Northern South China Sea: Inorganic Geochemical Evidence.
Sediments at marine cold seep areas provide potential archives of past fluid flow, which allow insights into the evolution of past methane seepage activities. However, signals for anaerobic oxidation of methane (AOM) might be obscured in bulk sediments in cold-seep settings due to several factors, especially flood and turbidite deposition. Comprehensive inorganic data were gathered in this study to explore the availability of related records at cold seeps and to provide insights into the evolution of past methane seepage activities. Sediments collected from the site 973-4 in the Taixinan Basin on the northern slope of the South China Sea were characterized in terms of total carbon and sulfur, δ13C values of total organic carbon (δ13CTIC), δ34S values of chromium reducible sulfur (δ34SCRS), and foraminiferal oxygen and carbon isotopes. The results confirmed a strong correlation between formation of authigenic minerals and AOM. Moreover, the 34S enrichments and abundant chromium reducible sulfur (CRS) contents in the authigenic sulfides in the sulfate-methane transition zone (SMTZ) within 619-900 cm below seafloor (cmbsf) reflected past high methane fluxes supported by constant methane seepages. Lithological distribution and AMS (Accelerator Mass Spectra) 14C dating of planktonic foraminifera show that the turbidite (~35.14 ka) was related to a foraminifera-rich interval (Unit II: 440-619 cmbsf) and increased carbonate productivity during the last glacial maximum (LGM). Enrichment of Mo and U was observed accompanied by low contents of nutrient metals (Al, Ti, V, Ni, Fe, Mn, and Cu) in Unit II. The foraminifera-rich interval (Unit II) of cold seep sediments was probably linked to the phenomenon of inconsecutive sedimentary sequence due to the turbidites, which resulted in the lack of Fe, Mn, and Ba enrichment. There is no U enrichment but only Mo enrichment within Unit III, which might be related to H2S produced by AOM during the methane seepages. Based on the above results, it can be speculated that this area has experienced multiple-episodes of methane seep events. Further exploration of AOM should focus on the risks of rapid deposition, especially the impact of turbidity current on sediments.


A Comparative Study of Self-Efficacy for Social Participation of People with Mental Illness in Japan and China.
Self-efficacy for social participation (SESP) of people with mental illness was examined in urban areas of Japan and China. The subjects were 266 people (140 Japanese, 126 Chinese) with mental illness who were living in their local community. Our SESP scale (SESP27) and the Rosenberg Self-Esteem Scale, Norbeck Social Support Questionnaire (NSSQ), Sense of Coherence measure (SOC13), General Health Questionnaire (GHQ12), and a self-administered questionnaire related to living conditions were used for data collection. Data were analyzed descriptively, correlations between scales were examined, and multiple regression analysis was performed by country. The results showed that annual income was related to SESP in Japan and China. Therefore, improvement of welfare and employment support for economic independence is likely to improve SESP of people with mental illness in both countries. In addition, SESP in people with mental illness is affected by self-esteem in Japan, and coping skills such as improvement of life functions in China. Thus, SESP is affected differently by the social, cultural and institutional characteristics of each country.


Introduction to the Centers for Disease Control and Prevention and the Healthcare Infection Control Practices Advisory Committee Guideline for the Prevention of Surgical Site Infections.
Surgical site infection (SSI) is a common type of health-care-associated infection (HAI) and adds considerably to the individual, social, and economic costs of surgical treatment. This document serves to introduce the updated Guideline for the Prevention of SSI from the Centers for Disease Control and Prevention (CDC) and the Healthcare Infection Control Practices Advisory Committee (HICPAC). The Core section of the guideline addresses issues relevant to multiple surgical specialties and procedures. The second procedure-specific section focuses on a high-volume, high-burden procedure: Prosthetic joint arthroplasty. While many elements of the 1999 guideline remain current, others warrant updating to incorporate new knowledge and changes in the patient population, operative techniques, emerging pathogens, and guideline development methodology.


A rapid and sensitive real-time PCR assay for the K65R drug resistance mutation in SIV reverse transcriptase.
Macaques infected with simian immunodeficiency virus (SIV) provide a suitable model for assessing the efficacy of antiretroviral (ARV) drug interventions and drug resistance selection associated with treatment. Resistance to the HIV reverse transcriptase inhibitor tenofovir continues to be examined in different treatment strategies in the macaque model. Evaluations of treatment interventions and drug resistance are hampered by the limited sensitivity of conventional population sequencing and the substantial effort involved in testing various tissue compartments in which viruses may reside. Therefore, a sensitive assay that permits simple and rapid testing for drug-resistant viruses would benefit appraisals of ARV treatments using in vivo models. To have this capability, we developed a real-time PCR-based assay for the detection of the SIV K65R reverse transcriptase mutation, a key marker for reduced susceptibility to tenofovir. Evaluations of SIV sequences yielded an assay detection limit mean of 0.4% mutant virus (range = 0.1-2%) in a wild-type background. In testing longitudinal plasma specimens from four SIV-infected macaques that received an active daily regimen of 30 mg/kg of tenofovir subcutaneously, the assay was able to detect K65R-positive viruses in all animals within 1-7 weeks after treatment began. The emerging mutants were initially present at frequencies estimated between 0.4% and 3%, below the detection capability of population sequencing. We propose the SIV K65R real-time PCR assay provides improved sensitivity and simplicity in studying tenofovir resistance in macaque models.


Spatial dynamics of masked picture repetition effects.
The aim of this study was to further elucidate the mechanisms of early and automatic object processing using a masked picture priming paradigm with both identity and exemplar repetition in functional MRI (fMRI). Masked repetition priming has been commonly used with words to isolate automatic, rapidly occurring mechanisms involved in visual word recognition; however, studies using the technique of masked priming with rapid presentation of pictures have been limited. This study demonstrates how the masked priming technique can be used to study early, automatic processing of rapidly presented complex objects. Temporal-occipital regions previously found to be sensitive to repetition priming in both masked word and unmasked picture studies were found to show repetition suppression for the identity primes only. Most notably, when divided into anterior and posterior divisions, the fusiform gyrus showed anatomically specific repetition suppression only in the posterior portion. This finding is comparable to that found in a previous study of masked word priming, and the similarity may suggest an overlap in the early identification processes for visual word form and visual object processing in this region. Finally, masked repetition of different exemplar objects did not result in reliable neural effects, suggesting that the underlying mechanisms of the more semantic-based, different exemplar priming may occur later or require the intervention of conscious processes.


Trends in toothbrushing and utilization of dental services in Finland.
Prevention and control of common dental diseases highly depends on individual behavior, and during the last decades, individuals have increasingly been required to take responsibility for their own oral health. In Finland the rate of toothbrushing and dental visits were first surveyed nationwide in 1971 by interviews with a sample of 1063 individuals, drawn to represent the total population aged 15 yr and over. At the time, 68% of the 829 dentulous interviewees claimed to brush at least once a day. Using another sample of 1006 interviewees, drawn in the same manner, in 1990 the brushing rate was found to have increased to 91% in 853 dentulous subjects. Daily brushing was more frequent among women (98%) than men (83%). The most distinct positive change regarding brushing frequency was found among men and those with only elementary education. In 1971 the interval between the two most recent dental visits was 1 yr or less for 44% of all the interviewees and for 25% it was more than 5 yr. In 1990, 53% of the interviewees had visited a dentist within a year and the visiting interval was more than 5 yr for 16%. The youngest subjects were the most frequent visitors: 60% of them in 1971 and 74% in 1990. The results indicate a clear trend toward more frequent brushing in Finland. However, this trend regarding dental visits does not seem to be equally remarkable.


Ultra-doped n-type germanium thin films for sensing in the mid-infrared.
A key milestone for the next generation of high-performance multifunctional microelectronic devices is the monolithic integration of high-mobility materials with Si technology. The use of Ge instead of Si as a basic material in nanoelectronics would need homogeneous p- and n-type doping with high carrier densities. Here we use ion implantation followed by rear side flash-lamp annealing (r-FLA) for the fabrication of heavily doped n-type Ge with high mobility. This approach, in contrast to conventional annealing procedures, leads to the full recrystallization of Ge films and high P activation. In this way single crystalline Ge thin films free of defects with maximum attained carrier concentrations of 2.20 ± 0.11 × 10(20) cm(-3) and carrier mobilities above 260 cm(2)/(V·s) were obtained. The obtained ultra-doped Ge films display a room-temperature plasma frequency above 1,850 cm(-1), which enables to exploit the plasmonic properties of Ge for sensing in the mid-infrared spectral range.


Allogeneic cell therapy from immunized donors with tumor antigen peptide enhances the antitumor effect after cyclophosphamide-using non-myeloablative allogeneic hematopoietic cell transplantation.
Non-myeloablative allogeneic stem cell transplantation is an option for the treatment of hematological malignancies as well as solid tumors. We recently proposed a cyclophosphamide-using non-myeloablative cell therapy in which donor lymphocytes infusion (DLI) was carried out after tolerance induction to donor cells. In this study, we tested the possibility that the cyclophosphamide-using cell therapy could be augmented by pre-immunization of donors before DLI. We initially assessed whether or not the cyclophosphamide-using cell therapy could also show antitumor effect against subcutaneously established colon 26 carcinoma. As a tumor antigen-derived peptide for colon 26, we used AH1, an immunodominant H-2Ld-binding peptide derived from the envelope protein (gp70) of an endogenous murine leukemia virus. The cyclophosphamide-using cell therapy with the DLI from donors which were pre-immunized with the AH1 peptide was compared with that from non-immunized mice. The cyclophosphamide-using cell therapy significantly suppressed subcutaneously established colon 26 carcinoma, and the tumor-rejected mice acquired the tumor-specific protective immunity. When combined with the DLI from donors that were immunized with AH1, antitumor effect of the cyclophosphamide-using cell therapy was significantly augmented. The DLI from tumor peptide-immunized donors showed no influence on donor chimerism and bodyweight of the treated mice, indicating no increased risk of graft-versus-host disease. Tumor-specific cytotoxic T lymphocytes could be generated from tumor-rejected mice. Our results indicate that the cyclophosphamide-using non-myeloablative cell therapy with the DLI from tumor peptide-immunized donors is a useful protocol to augment graft-versus-tumor effect without exacerbation of graft-versus-host disease.


Theory for anisotropic local ferroelectric switching.
Theoretical modeling of polarization switching around a biased tip contact is important for fundamental understanding and advanced applications of ferroelectrics. Here we propose a simple in-plane two-dimensional model that considers surface charge transport and the associated evolution of the electric field driving domain growth. The model reproduces peculiar domain shapes ranging from round to faceted in KTiOPO4(C2vsymmetry) and LiNbO3(C3vsymmetry). This is done through modulation of dielectric permittivity, which mimics domain wall pinning on the lattice. In contrast to previous works, which attempted to justify domain anisotropy by means of point symmetry invariants, here we illustrate the necessity of taking translational symmetry into account. The results are pertinent to ferroelectric racetrack memories and other applications requiring domain tailoring.


Hazards of drug use in the elderly. Commonsense measures to reduce them.
One of the major tasks of clinicians caring for elderly patients is preventing adverse drug reactions. This age-group is particularly at high risk for multiple pathologic findings and physical problems; therefore, increased drug use is common. Nondrug therapy should be employed whenever possible; however, if a drug is needed, the following interactions should be considered: drug-drug, drug-alcohol, drug-disease, and drug-nutrition. Successful management depends on good communication among all health care providers and with the patient, including use of written instructions and a patient medication record, and periodic review of both the dose prescribed and the need for the drug.


The Illinois Rape Myth Acceptance Scale-Subtle Version: Using an Adapted Measure to Understand the Declining Rates of Rape Myth Acceptance.
Research in recent years has shown decreased rates of rape myth acceptance. This decrease may be due to an actual decline in attitudes, but it may also be fully or in part because such attitudes have become socially undesirable to acknowledge. However, most of the current measures of rape myth acceptance are not sensitive to this issue. The purpose of the current study was to examine this issue by adapting the psychometrically sound items from the most established rape myth acceptance measure (the Illinois Rape Myth Acceptance Scale, IRMA) and combining those with additional items that may seem less problematic to endorse. Results showed that the revised measure (IRMA-S) elicited higher levels of rape myth acceptance than the original when both were administered to all participants, regardless of the order of administration. This suggests that the decrease may in fact be due more to measurement issues than real declines in rape myth acceptance. However, this difference was very small practically, amounting to the difference between some agreement and some disagreement on a single item. Previous research has found that the measurement method employed in this study has been successful when utilizing other items, so it may be that the IRMA-S was not sensitive enough to detect real-world differences, or that having both measures included in a single administration, even with filler measures between them, affected responses to the IRMA-S. Despite not conclusively resolving that main question, this study moves this important area of research forward in several ways, including adding to the literature on rape myth acceptance results from a more diverse sample than previous ones and providing findings on the impact of different facets of social desirability, as well as pointing the way toward continued research on measurement of rape myth acceptance.


Prognostic impact of urokinase-type plasminogen activator system components in clear cell renal cell carcinoma patients without distant metastasis.
Members of the urokinase-type plasminogen activator (uPA) system including uPA, its receptor uPAR and the plasminogen activator inhibitor 1 (PAI-1) play an important role in tumour invasion and progression in a variety of tumour types. Since the majority of clear cell renal cell carcinoma (ccRCC) shows distant metastasis at time of diagnosis or later, the interplay of uPA, uPAR and PAI-1 might be of importance in this process determining the patients' outcome. Corresponding pairs of malignant and non-malignant renal tissue specimens were obtained from 112 ccRCC patients without distant metastasis who underwent tumour nephrectomy. Tissue extracts prepared from fresh-frozen tissue samples by detergent extraction were used for the determination of antigen levels of uPA, uPAR and PAI-1 by ELISA. Antigen levels were normalised to protein concentrations and expressed as ng per mg of total protein. Antigen levels of uPA, uPAR, and PAI-1 correlated with each other in the malignant tissue specimens (rs=0.51-0.65; all P<0.001). Antigen levels of uPA system components were significantly higher in tissue extracts of non-organ confined tumours (pT3+4) compared to organ-confined tumours (pT1+2; all P<0.05). Significantly elevated levels of uPAR and PAI-1 were also observed in high grade ccRCC. When using median antigen levels as cut-off points, all three uPA system factors were significant predictors for disease-specific survival (DSS) in univariate Cox's regression analyses. High levels of uPA and uPAR remained independent predictors for DSS with HR=2.86 (95% CI 1.07-7.67, P=0.037) and HR=4.70 (95% CI 1.51-14.6, P=0.008), respectively, in multivariate Cox's regression analyses. A combination of high antigen levels of uPA and/or uPAR further improved the prediction of DSS in multivariate analysis (HR=14.5, 95% CI 1.88-111.1, P=0.010). Moreover, high uPA and/or uPAR levels defined a patient subgroup of high risk for tumour-related death in ccRCC patients with organ-confined disease (pT1+2) (HR=9.83, 95% CI 1.21-79.6, P=0.032). High levels of uPA and uPAR in tumour tissue extracts are associated with a significantly shorter DSS of ccRCC patients without distant metastases.


Cisapride versus placebo in reflux esophagitis. A multicenter double-blind trial.
In a 6 to 12-week double-blind trial, the effect of cisapride (10 mg q.i.d.) was compared with that of placebo in 63 patients with esophagitis confirmed by endoscopy and/or biopsy. In only one patient (3%) in the cisapride group but in 43% of the placebo patients (p = 0.001), symptoms had not improved after 6 weeks. Forty patients continued treatment until week 12. At that time, control endoscopy showed a significantly (p = 0.005) higher rate of healing (no erosions, ulcers, or bleeding mucosa) in the cisapride patients (63%) than in the placebo patients (12%). At week 12, only three of the 21 cisapride patients still had moderate reflux symptoms, whereas eight of the 19 placebo patients had moderate or severe symptoms (p less than 0.05). Cisapride patients also took significantly (p less than 0.001) less antacids during the trial. These results show that cisapride, 10 mg q.i.d., heals esophagitis lesions and greatly reduces associated symptoms. The treatment was well tolerated.


Promoting photosensitized reductive dechlorination of chlorothalonil using epigallocatechin gallate in water.
Chlorothalonil (CTL) is a broad-spectrum fungicide. Photodegradation is a main degradation pathway of CTL in water. Because of the high aquatic toxicity of CTL and its metabolite 4-hydroxy CTL (CTL-OH), it is significant to develop an effective method to degrade CTL but without formation of CTL-OH. Epigallocatechin gallate (EGCG) is an abundant tea byproduct and has more than 100-fold reducing power than vitamin C. The present study reports photosensitization effects of EGCG on CTL photodegradation in water under sunlight and artificial lights. The results indicated that EGCG significantly photosensitizes CTL photodegradation. Under high-pressure mercury light illumination, CTL underwent primarily reductive dechlorination. CTL-OH, a main CTL photolytic product, was not detected when EGCG was added in the water. We concluded that EGCG not only significantly enhances CTL photodegradation rate but also alters the photodegradation pathways, avoiding the production of the highly toxic CTL-OH. The results indicated high potential of using EGCG to minimize CTL aquatic toxicity and pollution.


Benchmarking and refining probability-based models for nucleosome-DNA interaction.
In investigations of nucleosome positioning preferences, a model that assigns an affinity to a given sequence is necessary to make predictions. One important class of models, which treats a nucleosome sequence as a Markov chain, has been applied with success when informed with experimentally measured nucleosomal sequence preferences. We find that we can also use such models as a fast approximative scheme for computationally expensive biophysical models, vastly increasing their reach. Employing these models in this way also allows us to benchmark them for the first time. Doing so for the approximative in silico models indirectly tells us about the accuracy we can expect of them when applied to real data. We find that models presented in the literature should perform well, but this performance depends on factors such as the order of the Markov model, the preprocessing of the probability distributions on which the model is based, and the size and quality of the sequence ensemble from which those distributions are calculated.


Regulation of eutrophication susceptibility in oligohaline regions of a northern Gulf of Mexico estuary, Mobile Bay, Alabama.
The factors regulating the eutrophication susceptibility of seven oligohaline regions in the sub-estuaries of Mobile Bay, Alabama were examined in a comparative analysis. The oligohaline regions differed primarily by the dominant land-use of their upstream watersheds, with two of the regions being primarily urban, two being primarily agricultural, and three being primarily forested. A stepwise model selection procedure was used to determine a suite of multiple regression models describing eutrophication response, in terms of a chlorophyll a (chla) on a sampling event basis, in relation to estuarine mixing time scales, nutrient concentrations, light availability, and watershed delivery of freshwater and nutrients. The models indicated a strong positive relationship between chla and mixing time scales (i.e., residence time or freshwater flushing time). Mixing time scales longer than five days allowed maximum chla (64 microg l(-1)), while lowest chla (< 1 microg l(-1)) occurred when mixing time scales were less than two days. Of the watershed inputs, chla exhibited opposing relationships with the components of freshwater load, having a negative relationship with discharge and a positive relationship with incoming freshwater nitrogen concentrations. Estuarine phosphorus concentrations and photosynthetically active radiation were also found to be good descriptors of chla. The comparative approach employed here allowed for the development of empirical models that were used to determine the nutrient concentration reductions required to achieve a trophic state of < 20 microg l(-1) chla. The average reductions in nitrogen and phosphorus needed to achieve this trophic state ranged from 0 to 32%.


Linac-based stereotactic radiosurgery (SRS) in the treatment of refractory trigeminal neuralgia: Detailed description of SRS procedure and reported clinical outcomes.
To present our linac-based SRS procedural technique for medically and/or surgically refractory trigeminal neuralgia (TN) treatment and simultaneously report our clinical outcomes. Twenty-seven refractory TN patients who were treated with a single fraction of 80 Gy to TN. Treatment delivery was performed with a 4 mm cone size using 7-arc arrangement with differential-weighting for Novalis-TX with six MV-SRS (1000 MU/min) beam and minimized dose to the brainstem. Before each treatment, Winston-Lutz quality assurance (QA) with submillimeter accuracy was performed. Clinical treatment response was evaluated using Barrow Neurological Institute (BNI) pain intensity score, rated from I to V. Out of 27 patients, 22 (81%) and 5 (19%) suffered from typical and atypical TN, respectively, and had median follow-up interval of 12.5 months (ranged: 1-53 months). For 80 Gy prescriptions, delivered total average MU was 19440 ± 611. Average beam-on-time was 19.4 ± 0.6 min. Maximum dose and dose to 0.5 cc of brainstem were 13.4 ± 2.1 Gy (ranged: 8.4-15.9 Gy) and 3.6 ± 0.4 Gy (ranged: 3.0-4.9 Gy), respectively. With a median follow-up of 12.5 months (ranged: 1-45 months) in typical TN patients, the proportion of patients achieving overall pain relief was 82%, of which half achieved a complete pain relief with BNI score of I-II and half demonstrated partial pain reduction with BNI score of IIIA-IIIB. Four typical TN patients (18%) had no response to radiosurgery treatment. Of the patients who responded to treatment, actuarial pain recurrence free survival rates were approximately 100%, 75%, and 50% at 12 months, 15 months, and 24 months, respectively. Five atypical TN patients were included, who did not respond to treatment (BNI score: IV-V). However, no radiation-induced cranial-toxicity was observed in all patients treated. Linac-based SRS for medically and/or surgically refractory TN is a fast, effective, and safe treatment option for patients with typical TN who had excellent response rates. Patients, who achieve response to treatment, often have durable response rates with moderate actuarial pain recurrence free survival. Longer follow-up interval is anticipated to confirm our clinical observations.


Knee Joint Loads and Surrounding Muscle Forces during Stair Ascent in Patients with Total Knee Replacement.
Total knee replacement (TKR) is commonly used to correct end-stage knee osteoarthritis. Unfortunately, difficulty with stair climbing often persists and prolongs the challenges of TKR patents. Complete understanding of loading at the knee is of great interest in order to aid patient populations, implant manufacturers, rehabilitation, and future healthcare research. Musculoskeletal modeling and simulation approximates joint loading and corresponding muscle forces during a movement. The purpose of this study was to determine if knee joint loadings following TKR are recovered to the level of healthy individuals, and determine the differences in muscle forces causing those loadings. Data from five healthy and five TKR patients were selected for musculoskeletal simulation. Variables of interest included knee joint reaction forces (JRF) and the corresponding muscle forces. A paired samples t-test was used to detect differences between groups for each variable of interest (p<0.05). No differences were observed for peak joint compressive forces between groups. Some muscle force compensatory strategies appear to be present in both the loading and push-off phases. Evidence from knee extension moment and muscle forces during the loading response phase indicates the presence of deficits in TKR in quadriceps muscle force production during stair ascent. This result combined with greater flexor muscle forces resulted in similar compressive JRF during loading response between groups.


Observation of optical properties and sources of aerosols at Buddha's birthplace, Lumbini, Nepal: environmental implications.
For the first time, aerosol optical properties are measured over Lumbini, Nepal, with CIMEL sunphotometer of the Aerosol Robotic Network (AERONET) program. Lumbini is a sacred place as the birthplace of Lord Buddha, and thus a UNESCO world heritage site, located near the northern edge of the central Indo-Gangetic Plains (IGP) and before the Himalayan foothills (and Himalayas) to its north. Average aerosol optical depth (AOD) is found to be 0.64 ± 0.38 (0.06-3.28) over the sampling period (January 2013-December 2014), with the highest seasonal AOD during the post-monsoon season (0.72 ± 0.44). More than 80% of the daily averaged AOD values, during the monitoring period, are above 0.3, indicating polluted conditions in the region. The levels of aerosol load observed over Lumbini are comparable to those observed at several heavily polluted sites in the IGP. Based on the relationship between AOD and Ångstrom exponent (α), anthropogenic, biomass burning, and mixed aerosols are found to be the most prevalent aerosol types. The aerosol volume-size distribution is bi-modal during all four seasons with modes centered at 0.1-0.3 and 3-4 μm. For both fine and coarse modes, the highest volumetric concentration of ~ 0.08 μm-3 μm-2 is observed during the post-monsoon and pre-monsoon seasons. As revealed by the single-scattering albedo (SSA), asymmetry parameter (AP), and refractive index (RI) analyses, aerosol loading over Lumbini is dominated by absorbing, urban-industrial, and biomass burning aerosols.


Single gene disorders come into focus--again.
In the early 1990s, when the second 5-year plan for the Human Genome Project-which requested more money than any previous research project in biology-was written, common disorders were presented as the future target of genome research. This was a clever move to ensure continued public support for this endeavor, which had been justified previously by the prospect that it would lead to the diagnosis, prevention, and therapy of severe, but mostly rare, Mendelian disorders. Today, more than 15 years later, after billions of dollars have been spent on genome-wide association studies (GWAS), very few major genetic risk factors for common diseases have been identified, and the enthusiasm for large GWAS is dwindling. At the same time, there is renewed interest for studying single gene disorders, which are now considered by some as a better clue to the understanding of common diseases. While this is probably true, Mendelian disorders are also important in their own right, since they must be far more common than generally thought. As discussed here, various efficient strategies exist for the elucidation of single gene defects, and their systematic application in combination with novel genome partitioning and massive parallel sequencing techniques, will have far-reaching implications for health care.


Methylation of inorganic and organic selenium by the bacterial thiopurine methyltransferase.
Escherichia coli cells expressing the tpm gene encoding the bacterial thiopurine methyltransferase (bTPMT) are shown to methylate selenite and (methyl)selenocysteine into dimethylselenide (DMSe) and dimethyldiselenide (DMDSe). E. coli cells expressing tpm from a gene library cosmid clone (harboring a Pseudomonas syringae insert of about 20 kb) also methylated selenate into DMSe and DMDSe. bTPMT is the first methyltransferase shown to be involved in the methylation of these selenium derivatives.


Inference of direct and multistep effective connectivities from functional connectivity of the brain and of relationships to cortical geometry.
The problem of inferring effective brain connectivity from functional connectivity is under active investigation, and connectivity via multistep paths is poorly understood. A method is presented to calculate the direct effective connection matrix (deCM), which embodies direct connection strengths between brain regions, from functional CMs (fCMs) by minimizing the difference between an experimental fCM and one calculated via neural field theory from an ansatz deCM based on an experimental anatomical CM. The best match between fCMs occurs close to a critical point, consistent with independent published stability estimates. Residual mismatch between fCMs is identified to be largely due to interhemispheric connections that are poorly estimated in an initial ansatz deCM due to experimental limitations; improved ansatzes substantially reduce the mismatch and enable interhemispheric connections to be estimated. Various levels of significant multistep connections are then imaged via the neural field theory (NFT) result that these correspond to powers of the deCM; these are shown to be predictable from geometric distances between regions. This method gives insight into direct and multistep effective connectivity from fCMs and relating to physiology and brain geometry. This contrasts with other methods, which progressively adjust connections without an overarching physiologically based framework to deal with multistep or poorly estimated connections. deCMs can be usefully estimated using this method and the results enable multistep connections to be investigated systematically.


Acoustic pressure wound therapy in the treatment of stage II pressure ulcers.
Pressure ulcers are localized skin injuries secondary to unrelieved pressure or friction. Patients with immobility issues are at increased risk for developing pressure ulcers. In 2004, stricter federal regulations for prevention and treatment of pressure ulcers in institutional settings--eg, long-term care facilities--were introduced. Effective, low-cost treatments for pressure ulcers are needed; acoustic pressure wound therapy (APWT), a noncontact, low-frequency, therapeutic ultrasound system, is one option. A retrospective case series of six long-term care patients (two men and one woman, age range 61 to 92 years), each with one Stage II pressure ulcer, is presented. Acoustic pressure wound therapy was provided as an adjunct to standard treatment that included balsam of Peru/castor oil/trypsin ointment, hydrogel, hydrocolloid dressings, silver dressings, and offloading. Outcomes (days to healing) were determined through changes in wound dimensions. Study participants each received APWT for 3 to 4 minutes three to four times weekly. In four of the six wounds, the average number of days to healing was 22. One of the two remaining patients discontinued treatment at 95% healed; treatment for the sixth patient was ongoing due to hospitalization that delayed APWT. In a long-term care setting, APWT added to standard of care may accelerate healing of Stage II pressure ulcers.


mtDNA analysis in ancient Nubians supports the existence of gene flow between sub-Sahara and North Africa in the Nile Valley.
The Hpal (np3,592) mitochondrial DNA marker is a selectively neutral mutation that is very common in sub-Saharan Africa and is almost absent in North African and European populations. It has been screened in a Meroitic sample from ancient Nubia through PCR amplification and posterior enzyme digestion, to evaluate the sub-Saharan genetic influences in this population. From 29 individuals analysed, only 15 yield positive amplifications, four of them (26.7%) displaying the sub-Saharan African marker. Hpa 1 (np3,592) marker is present in the sub-Saharan populations at a frequency of 68.7 on average. Thus, the frequency of genes from this area in the Merotic Nubian population can be estimated at around 39% (with a confidence interval from 22% to 55%). The frequency obtained fits in a south-north decreasing gradient of Hpa I (np3,592) along the African continent. Results suggest that morphological changes observed historically in the Nubian populations are more likely to be due to the existence of south-north gene flow through the Nile Valley than to in-situ evolution.


Scar burden by myocardial perfusion imaging predicts echocardiographic response to cardiac resynchronization therapy in ischemic cardiomyopathy.
About 30% of patients with heart failure do not respond to cardiac resynchronization therapy (CRT). We hypothesized that scar burden can predict poor response to CRT in patients with ischemic cardiomyopathy (ICM). Fifty patients (age, 68.5 +/- 9.2 years; 84% men; mean left ventricular ejection fraction (LVEF), 19.7% +/- 5.2%) with ICM who underwent CRT-defibrillator implantation and 201Tl single photon emission computed tomography myocardial perfusion imaging were included. Myocardial perfusion imaging studies were read quantitatively, generating a summed perfusion score (SPS). Left ventricular (LV) lead position was determined by chest radiography. Echocardiograms were performed before and after (median, 11.0 months) CRT. Echocardiographic response, defined as > or = 15% relative increase in LVEF, was documented in 28 (56%) patients. The mean SPS (18.8 +/- 11.3 vs 33.7 +/- 11.1; P = .000025) and the average scar density in the segments immediately adjacent to the LV lead (0.70 +/- 0.91 vs 1.64 +/- 0.82; P = .0004) were significantly lower in responders versus nonresponders. Global scar burden (r = -0.53; P = .00007), scar burden near the LV lead (r = -0.49; P = .0003), and the number of segments with a score of 4 (r = -0.53; P = .0007) inversely correlated with increase in LVEF after CRT. The hazard ratio for nonresponse increased with increasing tertiles of global SPS, scar density in the vicinity of the LV lead, and number of segments with transmural scar (ie, perfusion score = 4). Higher overall scar burden, a larger number of severely scarred segments, and greater scar density near the LV lead tip portend an unfavorable response to CRT in ICM patients. Prospective confirmation of these findings is warranted.


Cav3.1 (alpha1G) controls von Willebrand factor secretion in rat pulmonary microvascular endothelial cells.
The T-type Ca2+ channel Cav3.1 subunit is present in pulmonary microvascular endothelial cells (PMVECs), but not in pulmonary artery endothelial cells (PAECs). The present study sought to assess the role of Cav3.1 in thrombin-induced Weibel-Palade body exocytosis and consequent von Willebrand factor (VWF) release. In PMVECs and PAECs transduced with a green fluorescent protein (GFP)-tagged VWF chimera, we examined the real-time dynamics and secretory process of VWF-GFP-containing vesicles in response to thrombin and the cAMP-elevating agent isoproterenol. Whereas thrombin stimulated a progressive decrease in the number of VWF-GFP-containing vesicles in both cell types, isoproterenol only decreased the number of VWF-GFP-containing vesicles in PAECs. In PMVECs, thrombin-induced decrease in the number of VWF-GFP-containing vesicles was nearly abolished by the T-type Ca2+ channel blocker mibefradil as well as by Cav3.1 gene silencing with small hairpin RNA. Expression of recombinant Cav3.1 subunit in PAECs resulted in pronounced increase in thrombin-stimulated Ca2+ entry, which is sensitive to mibefradil. Together, these data indicate that VWF secretion from lung endothelial cells is regulated by two distinct pathways involving Ca2+ or cAMP, and support the hypothesis that activation of Cav3.1 T-type Ca2+ channels in PMVECs provides a unique cytosolic Ca2+ source important for Gq-linked agonist-induced VWF release.


CARDIORESPIRATORY EFFECTS OF DEXMEDETOMIDINE-BUTORPHANOL-MIDAZOLAM (DBM): A FULLY REVERSIBLE ANESTHETIC PROTOCOL IN CAPTIVE AND SEMI-FREE-RANGING CHEETAHS (ACINONYX JUBATUS).
Multiple anesthesia protocols have been used in the cheetah ( Acinonyx jubatus ). Twenty healthy, captive cheetahs were immobilized with dexmedetomidine (15.8 ± 1.9 μg/kg), butorphanol (0.22 ± 0.03 mg/kg), and midazolam (0.18 ± 0.03 mg/kg) by intramuscular injection. Induction, recumbency, and recovery times were recorded, and physiologic parameters were monitored. Anesthesia was antagonized with atipamezole (0.125 ± 0.02 mg/kg) and naltrexone (0.1 ± 0.014 mg/kg) intramuscularly. All cheetahs were safely anesthetized with this protocol. Cheetahs were laterally recumbent by 8 ± 3.5 min. Cardiorespiratory values were stable throughout the length of anesthesia. Moderate hypertension, with systolic blood pressure ranging from 178 ± 19.8 mm Hg, was initially observed but decreased over time. There was a statistical decreasing trend in temperature; SpO2; and systolic, mean, and diastolic blood pressure, but not in heart rate and end-tidal CO2. Recoveries were rapid, with cheetahs standing by 11.3 ± 5.7 min postreversal administration. This is the first report of a dexmedetomidine-butorphanol-midazolam anesthetic combination in cheetahs. Overall, this anesthetic protocol proved to be safe and effective.


Age-dependent Radiation Dose Rates from Canine Sn-117m Treatments.
Tin-117 m (Sn-117m) is used to treat dogs with osteoarthritic joints by radiosynoviorthesis. The decay process for Sn-117m is internal conversion wherein IC electrons and auger electrons provide the therapeutic effect. Additionally, the most prominent gamma emission is 158.6 keV. The effective dose rate received by a person interacting at close distances with a treated dog is needed to determine the person's total dose and thus regulatory compliance. Simple measurement of the dose rate at a given distance does not provide an accurate measurement of the effective dose to a person due to the non-uniform nature of the radiation field at close distances. MNCP models of the interactions of five ages of humans at three distances were created to determine the effective dose rates using the methodology from NRC Regulatory Guide 8.40. Ratios of the effective dose rate to the person to the measured dose rate at 1 m from the same source were calculated.


Effect of Peritumoral Bupivacaine on Primary and Distal Hyperalgesia in Cancer-Induced Bone Pain.
Cancer-induced bone pain (CIBP) is a debilitating chronic pain condition caused by injury to bone nerve terminals due to primary or metastasized bone tumors. Pain manifests as enhanced sensitivity, not only over the affected bone site but also at distal areas that share common nerve innervation with the tumor. In this study, we aim to understand how tumor-induced primary and distal pain sensitivities are affected by bupivacaine-induced block of bone nerve endings in a rat model of CIBP. MRMT-1 breast cancer cells were injected into the proximal segment of tibia in female Sprague-Dawley rats. Radiograms and micro-CT images were obtained to confirm tumor growth. Bupivacaine was injected peritumorally at day 7 or day 14 post-tumor induction, and withdrawal thresholds in response to pressure and punctate mechanical stimulus were recorded from the knee and hind-paw, respectively. Immunohistochemical studies for the determination of ATF3 and GFAP expression in DRG and spinal cord sections were performed. Rats developed primary and distal hyperalgesia after MRMT-1 administration that was sustained for 2 weeks. Peritumoral administration of bupivacaine in 7-day post-tumor-induced (PTI) rats resulted in a reversal of both primary and distal hyperalgesia for 20-30 mins. However, bupivacaine failed to reverse distal hyperalgesia in 14 day-PTI rats. ATF3 and GFAP expression were much enhanced in 14 day-PTI animals, compared to 7 day-PTI group. Results from this study strongly suggest that distal hyperalgesia of late-stage CIBP demonstrates differential characteristics consistent with neuropathic pain as compared to early stage, which appears more inflammatory in nature.


Laser capture microdissection technology.
Deciphering the cellular and molecular interactions that drive disease within the tissue microenvironment holds promise for discovering drug targets of the future. In order to recapitulate the in vivo interactions through molecular analysis, one must be able to analyze specific cell populations within the context of their heterogeneous tissue microecology. Laser capture microdissection is a method to procure subpopulations of tissue cells under direct microscopic visualization. Laser capture microdissection technology can harvest the cells of interest directly or can isolate specific cells by cutting away unwanted cells to give histologically pure enriched cell populations. A variety of downstream applications exist: DNA genotyping and loss-of-heterozygosity analysis, RNA transcript profiling, cDNA library generation, mass spectrometry proteomics discovery and signal pathway profiling.


Is there a Role for Gallium-67 Citrate SPECT/CT, in Patients with Renal Impairment or Who are Renal Transplant Recipients, in Identifying and Localizing Suspected Infection?
To assess the added value of single-photon emission computed tomography/computed tomography (SPECT/CT) in patients with end-stage renal failure (ESRF) or renal transplant recipients in whom focal infection was suspected. Gallium-67 (Ga-67) citrate scintigrams of 18 patients (10 in ESRF and eight with renal transplants) were reviewed. Sites of abnormal uptake seen on the whole body and SPECT were noted. A SPECT/CT was also reviewed to see if additional information could be obtained. Imaging results were compared with the final diagnosis. Overall, 14 out of 18 (78%) patients had a proven cause to explain symptoms while four patients did not have a final cause identified. Infection was proven in the final diagnosis in 12 out of 14 (86%) patients. Of the 10 patients with ESRF, six had confirmed infection with the Ga-67 citrate study correctly identifying five out of six (83%) patients, and SPECT/CT providing additional information in four out of five (80%) patients. In the eight renal transplant recipients, six had a confirmed source of infection (all identified by the Ga-67 citrate study). SPECT/CT provided additional information in two out of six (33%) patients. Ga-67 citrate imaging had an overall sensitivity of 13/14 (93%), with one false negative. SPECT/CT provided an additional contribution in eight out of 18 (44%) patients by better defining the location/extent of infection and differentiating the physiological from the pathological uptake.


Goos-Hänchen shifts of the reflected waves from a cold, inhomogeneous, and magnetized plasma slab.
We discuss theoretically the Goos-Hänchen (GH) shifts of the reflected waves from a cold, inhomogeneous, and magnetized plasma slab by using the invariant imbedding approach. Aiming at the linear and parabolic electron-density profiles, we demonstrate numerically the dependences of the co- and cross-polarized GH shifts on the angle of incidence, external static magnetic field, and the thickness of the plasma slab. The results show that the different electron-density profiles of plasma can result in the very different dependences of the GH shifts on the angle of incidence, external magnetic field, and the slab's thickness; the GH shifts can be switched between the considerably large positive and negative values under certain conditions. Particularly, without altering the structure of the plasma slab, the GH shifts can be manipulated by modifying the angle of incident or the external static magnetic field.


What Is the Most Effective Eccentric Stretching Position in Lateral Elbow Tendinopathy?
A variety of treatment options suggest that the optimal treatment strategy for lateral elbow tendinopathy (LET) is not known, and further research is needed to discover the most effective treatment for LET. The purpose of the present study was to verify the most effective position of eccentric stretching for the extensor carpi radialis brevis (ECRB) in vivo using ultrasonic shear wave elastography. A total of 20 healthy males participated in this study. Resting position was defined as 90° elbow flexion and neutral position of the forearm and wrist. Elongation of the ECRB was measured for four stretching maneuvers (forearm supination/pronation and wrist extension/flexion) at two elbow angles (90° flexion and full extension). The shear elastic modulus, used as the index of muscle elongation, was computed using ultrasonic shear wave elastography for the eight aforementioned stretching maneuverangle combinations. The shear elastic modulus was the highest in elbow extension, forearm pronation, and wrist flexion. The shear elastic moduli of wrist flexion with any forearm and elbow position were significantly higher than the resting position. There was no significant difference associated with elbow and forearm positions except for elbow extension, forearm pronation, and wrist flexion positions. This study determined that elbow extension, forearm pronation, and wrist flexion was the most effective eccentric stretching for the ECRB in vivo.


Intervention programme: a supported learning programme for educationally disadvantaged students.
The apartheid system of social engineering in South Africa enforced the segregation of racial groups. It lasted for 50 years, and had an impact on every aspect of society. It particularly affected the education system, resulting in inferior primary and secondary teaching of black learners. Ten years after the dissolution of apartheid, the consequences are still being felt in tertiary institutions. This legacy presents a challenge to South African medical schools, especially at a time of curriculum transformation. This paper describes how the issues of social and educational discrepancies are being addressed at the University of Cape Town.


Telemedicine-based digital retinal imaging vs standard ophthalmologic evaluation for the assessment of diabetic retinopathy.
To study the cost benefit analysis of using a telemedicine-based digital retinal imaging evaluation compared to conventional ophthalmologic fundus examination of diabetic patients for diabetic retinopathy. In this study, diabetic patients from Community Health Center, Inc. (CHCI), a large multi-site Federally Qualified Health Center) were evaluated by teleophthalmology using the Canon CR-1 nonmydriatic fundus camera. Digital images were acquired in the CHCI offices and saved on the EyePACS server network. The images were later evaluated by retinal specialists at the Yale Eye Center, Yale University Department of Ophthalmology and Visual Science. The costs for the standard of care ophthalmic examinations were calculated based on 2009 Medicaid reimbursement rates. The process of telemedicine-based diagnosis was based on a take-store-forward-visualize system. The cost of telemedicine-based digital retinal imaging examination included cost for devices, training, annual costs and a transportation fee. Current Medicaid reimbursement, transportation, and staff labor costs were used to calculate the conventional retinal examination cost as a comparison. Among the 611 patients digital retinal images screened in the first year of this program and for whom data are available, 166 (27.2%) cases of diabetic retinopathy were identified. Seventy-five (12.3%) patients screened positive with clinically significant disease and were referred for further ophthalmological evaluation and treatment. The primary direct cost of the telemedicine was $3.80, $15.00, $17.60, $1.50, and $2.50 per patient for medical assistant, ophthalmologist, capital cost (Equipment + Training), equipment maintenance, and transportation fee, respectively. The total cost in the telemedicine-based digital retinal imaging and evaluation was $40.40. The cost of conventional retinal examination was $8.70, $65.30, and $3.80 per patients for round-trip transportation, 2009 national Medicaid Physician Fee Schedule allowable for bilateral eye examination, and medical assistant personnel, respectively. The total costs of conventional fundus examination were $77.80. An additional conventional ophthalmologic retinal examination was required for 75 (12.3%) patients with clinically significant disease on telemedicine evaluation, which involves an averaged additional cost of $ 9.55 per patient for all the patients in the study. If the cost of subsequent examination was added, the total cost of telemedicine-based digital fundus imaging was $49.95 per patient in our group of 611 patients evaluated. Our cost analysis indicates that telemedicine-based diabetic retinopathy screening cost less ($49.95 vs $77.80) than conventional retinal examination and the telemedicine-based digital retinal imaging examination has the potential to provide an alternative method with greater convenience and access for the remote and indigent populations. Diabetes mellitus and diabetic retinopathy are growing problems in the United States and worldwide. Large scale adoption of telemedicine should be encouraged as a means toward providing improved access, increasing compliance with annual evaluation, at a low cost for patients with diabetes with direct access to an eye care specialist.


External carotid artery infusion with single-and multiple-drug regimens in the rat.
An animal model was constructed using retrograde cannulation of a branch of the external carotid artery of rats in order to study the intraarterial (IA) and systemic effects of bleomycine, methotrexate, and 5-fluorouracil on a squamous cell carcinoma implanted in both ears. Continuous seven-day IA infusion of bleomycine and 5-fluorouracil proved to be superior to the systemic way by about a factor of 3. Unfortunately, the tumor did not respond to methotrexate and therefore, for this drug, no conclusion could be made as to the relative benefits of IA administration. Comparing simultaneous, sequential, and intermittent multiple-drug regimens, the last one showed an antitumor effect which was superior to either of the other schedules. It is concluded that IA administration of effective cytotoxic drugs is a superior treatment modality and that in this model IA intermittent multiple-drug therapy is the most successful schedule yet studied.


Association Between Sleep Efficiency and Hypertension in Chinese Obstructive Sleep Apnea Patients.
We aimed to explore the relationship of sleep efficiency (SE) with the prevalence of hypertension in Chinese obstructive sleep apnea (OSA) patients based on polysomnography (PSG) records. We studied 2360 patients with OSA and 764 primary snorers who underwent PSG in our hospital. SE was divided into three grades, including ≥85%, 80%~84.9%, and <80%. Hypertension was defined based either on direct blood pressure measurements, under anti-hypertensive treatments or on physician diagnosis. Multivariate logistic regression models were conducted to investigate the association between SE and hypertension. After adjusting for potential confounding factors, OSA patients with <80% SE and those with 80% to 84.9% SE were significantly associated with the prevalence of hypertension (OR = 1.248, 95% CI 1.018~1.531, P=0.033; OR = 1.380, 95% CI 1.040~1.832, P=0.026). Compared to primary snorers, OSA combined with <85% SE increased the odds of hypertension. In stratified analysis by SE, risk of hypertension only in those with <80% SE was significantly different between OSA and primary snorers. Furthermore, this relationship between reduced SE and hypertension was evident especially in female, younger ages, obese, moderate and severe OSA patients. No significant relationship between reduced SE and hypertension was found in primary snores group. We found that poor SE was correlated with the prevalence of hypertension in Chinese OSA patients, but not in those with primary snoring. Moreover, this relationship was evident especially in female, younger ages, obese, moderate and severe OSA patients.


The structure of a human neurofilament gene (NF-L): a unique exon-intron organization in the intermediate filament gene family.
We have cloned and determined the nucleotide sequence of the human gene for the neurofilament subunit NF-L. The cloned DNA contains the entire transcriptional unit and generates two mRNAs of approx. 2.6 and 4.3 kb after transfection into mouse L-cells. The NF-L gene has an unexpected intron-exon organization in that it entirely lacks introns at positions found in other members of the intermediate filament gene family. It contains only three introns that do not define protein domains. We discuss possible evolutionary schemes that could explain these results.


Quiescence, cycling, and turnover in the primitive hematopoietic stem cell compartment.
Continuous oral bromodeoxyuridine (BrdU) administration was used for the non-invasive measurement of the in vivo cell cycling characteristics of hematopoietic stem and progenitor cell populations of increasing maturity, isolated on the basis of their relative levels of Rhodamine 123 (Rh) and Hoechst 33342 (Ho) fluorescence. The results showed that whereas primitive hematopoietic stem cells (PHSCs) are hierarchically ordered on the basis of quiescence, the most primitive of these, characterized by their Rh/Ho(dull) phenotype and their capacity for long-term hematopoietic reconstitution, are not dormant, but cycle slowly in normal steady-state bone marrow (BM). Cell cycle analysis showed that 30 +/- 7% of Rh/Ho(dull) PHSCs had cycled and incorporated BrdU following continuous administration over 1 week, whereas 60 +/- 14% and 89 +/- 3% of these cells were BrdU positive at 4 and 12 weeks, respectively. Linear regression analysis of these data showed that Rh/Ho(dull) PHSCs cycle with an average turnover time of 4.3 weeks (30 days), and a t1/2 (time to 50% cycled) of 2.75 weeks (19 days).


Enhancement of K transfer to intracellular fluid by cerebral artery K-loading.
Intact, UL, and pancreatectomized UL dogs were loaded with K by administration of 2 mEq KCl/kg/hr through a cerebral (vertebral) artery. K transfer to ICF was calculated and compared with that computed in control animals K-loaded through a PV. At the same rate of K administration, the change of route from PV to VA markedly increased transmembrane K transfer, even in the absence of insulin; the increase seems a specific response to K. KCl administration via a VA, with a resulting abrupt rise in the serum K concentration of cerebral blood, activates a K transfer mechanism (possibly by stimulation of a K-sensitive CNS receptor) that is strikingly unlike the insulin-mediated one stimulated by intravenous KCl. Hyperkalemic dogs may have more than one mechanism for maintaining K homeostasis, depending on the rate at which K enters the circulation.


Bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy: a report of three cases.
To report three cases of bilateral primary choroidal melanoma treated with bilateral plaque radiotherapy. Retrospective, single-center case series. Case 1: In 1981, a 50-year-old man was diagnosed with a 5-mm-thick choroidal melanoma in the right eye (OD) and treated with plaque radiotherapy. In 1994, a 6.8-mm-thick choroidal melanoma in the left eye (OS) was treated with plaque radiotherapy. Final visual acuity was light perception OD and 20/20 OS at 24 years follow-up. Case 2: In 1983, a 53-year-old woman was diagnosed with a 3.5-mm-thick choroidal melanoma OS and treated with plaque radiotherapy. In 2001, an enlarging 2.5-mm-thick choroidal melanoma OD was treated with plaque radiotherapy. Final visual acuity was 20/30 OD and 20/20 OS at 22 years follow-up. Case 3: In 2001, a 92-year-old man was diagnosed with a 7.9-mm-thick choroidal melanoma OD treated with plaque radiotherapy. In 2003, an enlarging 2.8-mm-thick juxtapapillary choroidal melanoma was treated with plaque radiotherapy. Final visual acuity was 20/70 OD and 20/60 OS at 2.5 years follow-up. No patient showed ocular melanocytosis. Stable tumor regression was achieved in all six eyes. Metastatic disease did not develop in any case over 16 years of follow-up. Monitoring of both eyes of patients with uveal melanoma is important for the remote possibility of melanoma in the second eye. In these three patients, plaque radiotherapy allowed for preservation of the globes and some vision.


Milk protein hydrolysates activate 5-HT(2C) serotonin receptors: influence of the starting substrate and isolation of bioactive fractions.
Milk protein hydrolysates generated with different starting substrates, including sodium caseinate (NaCN), acid casein (Acid CN), skim milk powder (SMP) and glycomacropeptide (GMP) were demonstrated to behave as serotonin 2C (5-HT(2C)) receptor agonists. The 5-HT(2C) receptor activating potential of NaCN hydrolysates correlated with an increased protein hydrolysis, most likely due to enhanced release of bioactive peptides over the time course of hydrolysis. In its unhydrolysed form, GMP was the only starting substrate showing 5-HT(2C) serotonin receptor agonist activity. The 5-HT(2C) serotonin receptor agonist activity of its corresponding hydrolysate (GMPH-240 min) was significantly higher (P < 0.05). Fractionation of the 240 min NaCNH using ultrafiltration (UF), solid-phase extraction (SPE), semi-preparative reverse-phase high performance liquid chromatography (RP-HPLC) and isoelectric focusing (IEF) was carried out. Characterisation of the fractions obtained shows that the bioactive peptides had a relatively low molecular mass (<1 kDa), were hydrophobic in nature and had a pI between 8.6 and 13.2. These different physicochemical characteristics together with the stability of NaCNH-240 min to simulated intestinal digestion, allow prediction of a favourable outcome regarding the bioavailability of the bioactive peptides therein. These results reinforce the potential of milk-derived bioactive peptides to be developed into functional foods targeted at 5-HT(2C) receptor modulation.


Effect of dietary fibre on postprandial thermogenesis.
The effect of fibre on postprandial thermogenesis was evaluated in seven healthy males (age 29.6 +/- 3.6 years, BMI 24.6 +/- 0.6 kg/m2) after they had ingested three isocaloric meals with different fibre contents: low fibre (Lfb) containing 8 g. dietary fibre; glucomannan (Glc), which was Lfb supplemented with 6 g glucomannan, a pectin-like fibre; and high fibre (Hfb) containing 26 g dietary fibre. Postprandial thermogenesis, evaluated for 6 h after the ingestion of food, was higher after the Lfb (82.3 +/- 5.4 kcal) than after the Hfb and Glc meals (69.4 +/- 6.8 and 61.4 +/- 8.4 kcal, respectively). Glucose and insulin responses were depressed over the first 2 h after the Hfb and Glc meals as compared to the Lfb meal. However, these differences disappeared when the whole 6 h postprandial period was considered. No major effects of the different fibre contents of the meals on postprandial triglyceride and FFA levels were detected. These results demonstrate that the fibre content of meals, besides the well known effect on energy intake, may also affect energy expenditure.


Chirality-Induced Spin Selectivity in Supramolecular Chirally Functionalized Graphene.
Chiral graphene hybrid materials have attracted significant attention in recent years due to their various applications in the areas of chiral catalysis, chiral separation and recognition, enantioselective sensing, etc. On the other hand, chiral materials are also known to exhibit chirality-dependent spin transmission, commonly dubbed "chirality induced spin selectivity" or CISS. However, CISS properties of chiral graphene materials are largely unexplored. As such, it is not clear whether graphene is even a promising material for the CISS effect given its weak spin-orbit interaction. Here, we report the CISS effect in chiral graphene sheets, in which a graphene derivative (reduced graphene oxide or rGO) is noncovalently functionalized with chiral Fmoc-FF (Fmoc-diphenylalanine) supramolecular fibers. The graphene flakes acquire a "conformational chirality" postfunctionalization, which, combined with other factors, is presumably responsible for the CISS signal. The CISS signal correlates with the supramolecular chirality of the medium, which depends on the thickness of graphene used. Quite interestingly, the noncovalent supramolecular chiral functionalization of conductive materials offers a simple and straightforward methodology to induce chirality and CISS properties in a multitude of easily accessible advanced conductive materials.


Observation of H2 aggregation onto a doubly charged anion in a temperature-controlled ion trap.
Hydrogen is the second most difficult gas to be condensed due to its weak intermolecular interactions. Here we report observation of H(2) aggregation onto a doubly charged anion, (-)O(2)C(CH(2))(12)CO(2)(-)(DC(2-)). Weakly bound DC(2-)(H(2))(n) clusters were formed in a temperature-controlled ion trap and studied using photoelectron spectroscopy. The onset of clustering was observed at 30 K, whereas extensive condensation was observed at 12 K with n up to 12. Photoelectron spectra were obtained for DC(2-)(H(2))(n) (n = 0-6) at 193 and 266 nm. The spectra of DC(2-)(H(2))(n) were observed to be identical to that of the bare DC(2-) dianion except a slight blue shift, indicating the weak interactions between H(2) and the parent dianion. The blue shift on average amounts to approximately 34 meV (3.3 kJ/mol) per H(2), which represents the lower limit of the H(2) binding energy to DC(2-).


Cloning and characterization of the 5'-flanking region of the rat P4Halpha gene encoding the prolyl 4-hydroxylase alpha(I) subunit.
Prolyl 4-hydroxylase (P4H), an alpha(2)beta(2) tetramer, plays a crucial role in collagen synthesis. It catalyzes the hydroxylation of proline residues in X-Pro-Gly sequences to form 4-hydroxyproline. We isolated a genomic clone of the rat P4Halpha(I) gene. Approx. 0.6 kb of the fragment, which contained the 5'-flanking region, exon 1, and intron 1, was sequenced. Computer analysis revealed several motifs that may act as binding sites for basal transcription factors. To elucidate the regulation of the rat P4Halpha(I) gene expression, we assessed the 0.6 kb 5'-flanking region of the P4Halpha(I) gene for basal promoter activity. A series of deletion mutants of the 5'-flanking region linked to the luciferase gene was constructed. The basal expression level of these constructs was determined in fetal rat lung fibroblasts and Hepa-1 hepatoma cells. By measuring the luciferase activity, we found a positive-regulatory region at positions -246 to -165 bp.


Diagnostic impact of integrated 18F-FDG PET/MRI in cerebral staging of patients with non-small cell lung cancer.
Background Integrated positron emission tomography/magnetic resonance imaging (PET/MRI) systems are increasingly being available and used for staging examinations. Brain metastases (BM) are frequent in patients with non-small cell lung cancer (NSCLC) and decisive for treatment strategy. Purpose To assess the diagnostic value of integrated 18F-2-fluoro-2-deoxy-D glucose (18F-FDG) PET/MRI in initial staging in patients with NSCLC for BM in comparison to MRI alone. Material and Methods Eighty-three patients were prospectively enrolled for an integrated 18F-FDG PET/MRI examination. The 3 T MRI protocol included a fluid-attenuated inversion-recovery sequence (FLAIR) and a contrast-enhanced three-dimensional magnetization prepared rapid acquisition GRE sequence (MPRAGE). Two neuroradiologists evaluated the datasets in consensus regarding: (i) present lesions; (ii) size of lesions; and (iii) number of lesions detected in MRI alone, compared to the PET component when reading the 18F-FDG PET/MRI. Results Based on MRI alone, BM were detected in 15 out of the 83 patients, comprising a total of 39 metastases. Based on PET alone, six patients out of the 83 patients were rated positive for metastatic disease, revealing a total of 15 metastases. PET detected no additional BM. The size of the BM correlated positively with sensitivity of detection in PET. Conclusion The sensitivity of PET in detection of BM depends on their size. 18F-FDG PET/MRI does not lead to an improvement in diagnostic accuracy in cerebral staging of NSCLC patients, as MRI alone remains the gold standard.


Neural networks for estimating intrinsic dimension.
We consider the problem of feature extraction and determination of intrinsic dimensionality of observation data. One of the common approaches to this problem is to use autoassociative neural networks with a "bottleneck" projecting layer. We propose a different approach in which a neural network performs a topological mapping that creates a nonlinear lower-dimensional projection of the data. The mapping preserves relative distances of neighbors. This technique can be efficiently implemented with the help of radial basis function networks, and it is significantly faster than training an autoassotiative network. We show that the proposed technique can be used for estimating the dimension of minimal mathematical model from time series data.


Characterization of quorum sensing and quorum quenching soil bacteria isolated from Malaysian tropical montane forest.
We report the production and degradation of quorum sensing N-acyl-homoserine lactones by bacteria isolated from Malaysian montane forest soil. Phylogenetic analysis indicated that these isolates clustered closely to the genera of Arthrobacter, Bacillus and Pseudomonas. Quorum quenching activity was detected in six isolates of these three genera by using a series of bioassays and rapid resolution liquid chromatography analysis. Biosensor screening and high resolution liquid chromatography-mass spectrometry analysis revealed the production of N-dodecanoyl-L-homoserine lactone (C12-HSL) by Pseudomonas frederiksbergensis (isolate BT9). In addition to degradation of a wide range of N-acyl-homoserine lactones, Arthrobacter and Pseudomonas spp. also degraded p-coumaroyl-homoserine lactone. To the best of our knowledge, this is the first documentation of Arthrobacter and Pseudomonas spp. capable of degrading p-coumaroyl-homoserine lactone and the production of C12-HSL by P. frederiksbergensis.


Characterization of an antigen defined by monoclonal antibody KMO1.
We have isolated an antigen defined by the monoclonal antibody KMO1 from tissue culture supernatant as a glycoprotein and from cancer cells as a glycolipid. The antigenic determinant was a carbohydrate. Antibody KMO1 inhibited the binding activity of 19-9 to CA19-9, but 19-9 antibody did not inhibited the binding activity of KMO1 to KMO1 antigen. The glycolipid antigen of KMO1 was a monosialoganglioside and was separated into 3 components on thin layer chromatography. The 19-9 antibody reacted with one of the components. These results suggest that the KMO1 antigen is similar to but not identical to CA19-9.


Postoperative analgesia by adding acupuncture to conventional therapy, a non-randomized controlled trial.
Background Postoperative pain is common in patients hospitalized in surgical departments, yet it is currently not sufficiently controlled by analgesics. Acupuncture, a complementary medical practice, has been evaluated for its benefits in postoperative pain with heterogeneous results. We tested the feasibility of a controlled study comparing the postoperative analgesic effect of acupuncture together with standard-of-care to standard-of-care only. Methods In this pilot non-randomized controlled study conducted at a tertiary medical center in Israel, patients received either acupuncture with standard-of-care pain treatment (acupuncture group) or standard-of-care treatment only (control group) following surgery. Visual Analogue Scale (VAS) ratings for pain level at rest and in motion were evaluated both at recruitment and two hours after treatment. Acupuncture-related side effects were reported as well. Results We recruited 425 patients; 336 were assigned to the acupuncture group and 89 to the control group. The acupuncture group exhibited a decrease of at least 40% in average level of pain both at rest (1.8±2.4, p<0.0001) and in motion (2.1±2.8, p<0.0001) following acupuncture, whereas the control group exhibited no significant decrease (p=0.92 at rest, p=0.98 in motion). Acupuncture's analgesic effect was even more prominent in reducing moderate to severe pain at baseline (VAS ≥4), with a decrease of 49% and 45% of pain level at rest and in motion respectively (p<0.001), compared with no significant amelioration in the control group (p=0.20 at rest, p=0.12 in motion). No major side effects were reported. Conclusion Integrating acupuncture with standard care may improve pain control in the postoperative setting.


A case of hyponatremia in panhypopituitarism caused by the primary empty sella syndrome.
A 64-year-old woman was admitted for evaluation of hyponatremia. She was maintained on hypertonic saline administration. Without this therapy, the serum Na concentration decreased progressively to 127 mEq/L and the plasma osmolality to 254 mOsm/Kg H2O, on Day 3. At that time, the concentration of antidiuretic hormone (ADH) was as high as 3.5 pg/ml. A skull radiogram revealed an enlarged sella turcica. Computed tomography (CT) revealed a low density in the sella, and magnetic resonance imaging revealed equal intensity of the sella turcica and the cerebrospinal fluid. A diagnosis of empty sella syndrome was made by metrizamide cisternography in conjunction with CT scanning. A diagnosis of panhypopituitarism was made by endocrine function tests. 123I-thyroidal uptake was 6% when her serum TSH was 10.9 microU/ml, suggesting that she might also have primary hypothyroidism. When this patient was given glucocorticoid before levothyroxine replacement, her serum Na concentration rose up to about 140 mEq/L and a normal relationship between her plasma ADH level (2.4 pg/ml) and plasma osmolality (281 mOsm/kg H2O) was restored. Therefore, it was suggested that ADH hypersecretion induced by the glucocorticoid deficiency might in part contribute to the development of hyponatremia. This is the case of primary empty syndrome associated with panhypopituitarism, in whom initial symptom was caused by hyponatremia.


Spectrum of magnetic resonance imaging findings in congenital lumbar spinal stenosis.
To investigate whether congenital lumbar spinal stenosis (CLSS) is associated with a specific degenerative changes of the lumbar spine. The lumbar spine magnetic resonance imaging studies of 52 subjects with CLSS and 48 control subjects were retrospectively evaluated. In each examination, the five lumbar levels were assessed for the presence or absence of circumferential or shallow annular bulges, annular tears, anterior or posterior disc herniations, epidural lipomatosis, Schmorl's nodes, spondylolisthesis, pars defects, and stress reactions of the posterior vertebral elements. Compared to control individuals, subjects with CLSS exhibited increased incidence of circumferential and shallow annular bulges, annular tears, disc herniations and spondylolisthesis (P < 0.05). CLSS is associated with increased incidence of degenerative changes in specific osseous and soft-tissue elements of the lumbar spine.


[Antibiotic pharmacokinetics in patients with mucoviscidosis].
In this review we summarize the available literature on the pharmacokinetics of antibacterials in cystic fibrosis. A special impact is given on the results of our group which will be put in perspective with the results of other authors. The homogeneity of our patient population allows a valid comparison between patient and volunteer data. We do not confirm the previously suggested strongly enhanced elimination of antibacterials in CF. Our findings have recently been confirmed by other investigators. However, since in the clinical situation a more heterogeneous group of patients is treated it seems rational to increase the dose of the antibacterials by about 20-30%.


A review of the prevalence, utility, and caveats of using chloroplast simple sequence repeats for studies of plant biology.
Microsatellites occur in all plant genomes and provide useful markers for studies of genetic diversity and structure. Chloroplast microsatellites (cpSSRs) are frequently targeted because they are more easily isolated than nuclear microsatellites. Here, we quantified the frequency and uses of cpSSRs based on a literature review of over 400 studies published 1995-2013. These markers are an important and economical tool for plant biologists and continue to be used alongside modern genomics approaches to study genetic diversity and structure, evolutionary history, and hybridization in native and agricultural species. Studies using species-specific primers reported a greater number of polymorphic loci than those employing universal primers. A major disadvantage to cpSSRs is fragment size homoplasy; therefore, we documented its occurrence at several cpSSR loci within and between species of Acmispon (Fabaceae). Based on our empirical data set, we recommend targeted sequencing of a subset of samples combined with fragment genotyping as a cost-efficient, data-rich approach to the use of cpSSRs and as a test of homoplasy. The availability of genomic resources for plants aids in the development of primers for new study systems, thereby enhancing the utility of cpSSRs across plant biology.


[Optimizing resources to reduce costs to determine HIV viral load in limited resources settings].
HIV viral load testing is a key factor to evaluate the accomplishment of the UNAIDS target of 90% of viral suppression among people receiving antiretroviral therapy. Pooled samples are a potentially accurate and economic approach in resource-constrained settings, but efficiency can be negatively affected by high prevalence rates of virological failure. Strategies were assessed to increase the relative efficiency of pooled HIV viral load testing in resource-constrained settings. We evaluated two strategies: a) plasma samples were not included in pools if patients had <12 months on antiretroviral therapy, patients had previous viral load >1,000 copies/ml, or were antiretroviral therapy naïve patients, and b) plasma pools were organized separately for first and second-line antiretroviral therapy regimens. Individual viral load tests were used to compare pooled results. Negative predictive values were similar for patients on first (100.0%; 95% CI 99.5 to 100.0) and second-line antiretroviral therapy regimens (99.4%; 95% CI 96.9 to 99.9). However, the incidence of virological failure among individuals on first-line antiretroviral therapy was lower than second-line antiretroviral therapy patients (p <0.01), resulting in greater savings in laboratory tests in patients on first-line antiretroviral therapy (74.0%; 95% CI 71.0 to 76.7) compared with the group of patients on second-line antiretroviral therapy (50.9%; 95% CI 44.4 to 57.3) (p<0.01). Selecting the samples to be included in the pools and selecting the pools according to ART regimens are criteria that could lead to decreased spending on laboratory tests for HIV viral load determination in resource-constrained settings.


BosR Is A Novel Fur Family Member Responsive to Copper and Regulating Copper Homeostasis in Borrelia burgdorferi.
The ferric uptake regulator (Fur) family of DNA-binding proteins represses and/or activates gene transcription via divalent metal ion-dependent signal sensing. The Borrelia burgdorferi Fur homologue, also known as Borrelia oxidative stress regulator (BosR), promotes spirochetal adaptation to the mammalian host by directly repressing the lipoproteins required for tick colonization and indirectly activating those required for establishing infection in the mammal. Here, we examined whether the DNA-binding activity of BosR was regulated by any of the four most prevalent transition metal ions in B. burgdorferi, Mn, Fe, Cu, and Zn. Our data indicated that in addition to a structural site occupied by Zn(II), BosR had two regulatory sites that could be occupied by Zn(II), Fe(II), or Cu(II) but not by Mn(II). While Fe(II) had no effect, Cu(II) and Zn(II) had a dose-dependent inhibitory effect on the BosR DNA-binding activity. Competition experiments indicated that Cu(II) had a higher affinity for BosR than Zn(II) or Fe(II). A BosR deficiency in B. burgdorferi resulted in a significant increase in the Cu level but no significant change in the levels of Mn, Fe, or Zn. These data suggest that Cu regulates BosR activity, and BosR in turn regulates Cu homeostasis in B. burgdorferi While this regulatory paradigm is characteristic of the Fur family, BosR is the first one shown to be responsive to Cu(II), which may be an adaptation to the potentially high level of Cu present in the Lyme disease spirochete.IMPORTANCE Transition metal ions serve an essential role in the metabolism of all living organisms. Members of the ferric uptake regulator (Fur) family play critical roles in regulating the cellular homeostasis of transition metals in diverse bacteria, and their DNA-binding activity is often regulated by coordination of the cognate divalent metal ions. To date, regulators with metal ion specificity to Fe(II), Mn(II), Zn(II), and Ni(II) have all been described. In this study, we demonstrate that BosR, the sole Fur homologue in Borrelia burgdorferi, is responsive to Cu(II) and regulates Cu homeostasis in this bacterium, which may be an adaption to potentially Cu-rich milieu in the Lyme disease spirochete. This study has expanded the repertoire of the Fur family's metal ion specificity.


Magneto-optical detection of spin accumulation under the influence of mechanical rotation.
The generation of spin-polarised carriers in a non-magnetic material holds the key to realise highly efficient spintronic devices. Recently, it has been shown that the large spin-orbit coupling can generate spin-polarised currents in noble metals such as tungsten and platinum. Especially, if small samples of such metals are rotated on a plane disc in the presence of a perpendicular magnetic field, the orbital angular momentum is altered leading to a segregation of spin up and spin down electrons, i.e., a spin current in the samples. This is manifested via an induced magnetic moment on the metal. In this letter, magneto-optical Kerr effect (MOKE) is used to detect induced magnetic moments which allows remote measurements on metal samples rotating at 100~210 Hz. Our results confirm the mechanical generation of spin-polarised currents via optical detection of spin accumulation.


Effects of the nitric oxide synthase inhibitor ronopterin (VAS203) on renal function in healthy volunteers.
Reduced nitric oxide (NO) availability may adversely affect renal perfusion and glomerular filtration. The aim of the present study was to characterize in detail the pharmacological effects of VAS203, an inhibitor of NO synthase, on renal haemodynamics in humans. This double-blind, randomized, placebo-controlled, cross-over phase-I-study comprised 18 healthy men. Renal haemodynamics were assessed with constant-infusion input-clearance technique with p-aminohippurate and inulin for renal plasma flow (RPF) and glomerular filtration rate (GFR), respectively. After baseline measurement, a constant infusion of the tetrahydrobiopterin analogue ronopterin (VAS203, total 10 mg/kg body weight) or placebo was administered at random order for 6 hours additionally. After a wash-out phase of 28 days, the second course was applied. In parallel, markers of early kidney injury and renal function were assessed repeatedly up to 48 hours after starting VAS203/placebo-infusion. VAS203-infusion resulted in a significant decrease of RPF (P < .0001) and GFR (P < .001) compared to placebo, but magnitude was within the physiological range. RPF and GFR recovered partly 2 hours after end of VAS203-infusion and was normal at beginning of the second infusion period. Compared to placebo, preglomerular resistance (P < .0001), and to lesser extent postglomerular resistance (P < .0001) increased, resulting in a decrease of intraglomerular pressure (P < .01). No treatment related effect on markers of early kidney injury, and on renal function (P for all >.20) have been observed. Our phase-I-study in healthy humans indicates that VAS203 (10 mg/kg body weight) reduces renal perfusion and glomerular function within the physiological range mainly due to vasoconstriction at the preglomerular site.


A method based on local density and random walks for complexes detection in protein interaction networks.
In this paper, we present a method based on local density and random walks (LDRW) for core-attachment complexes detection in protein-protein interaction (PPI) networks whether they are weighted or not. Our LDRW method consists of two stages. Firstly, it finds all the protein-complex cores based on local density of subnetwork. Then it uses random walks with restarts for finding the attachment proteins of each detected core to form complexes. We evaluate the effectiveness of our method using two different yeast PPI networks and validate the biological significance of the predicted protein complexes using known complexes in the Munich Information Center for Protein Sequence (MIPS) and Gene Ontology (GO) databases. We also perform a comprehensive comparison between our method and other existing methods. The results show that our method can find more protein complexes with high biological significance and obtains a significant improvement. Furthermore, our method is able to identify biologically significant overlapped protein complexes.


Comparisons of Waist Circumference Measurements at Five Different Anatomical Sites in Chinese Children.
This study compared the waist circumference (WC) measurements of Chinese children at different sites to determine the relationship between WC measurements and body fat. WC was measured at five sites in 255 subjects aged 9-19 years: immediately below the lowest rib (WC1), at the narrowest waist (WC2), the midpoint between the lowest rib and the iliac crest (WC3), 1 cm above the umbilicus (WC4), and immediately above the iliac crest (WC5). Body fat mass (FM), body fat percentage (% BF), body fat mass in the trunk (FM in the trunk), and fat percentage in the trunk (% BF in the trunk) were determined by dual-energy X-ray absorptiometry. The WCs were then compared through ANOVA with repeated measurement. The relationship of WC of each site with FM, % BF, FM in the trunk, and % BF in the trunk was examined through partial correlation. The WCs exhibited the following pattern: WC2 < WC1 < WC3 < WC4 < WC5 (p < 0.001) in males and WC2 < WC1 < WC4, WC3 < WC5 (p < 0.001) in females. The measured WCs were strongly correlated with FM, % BF, FM in the trunk, and % BF in the trunk. The WC measurements at five commonly used sites among Chinese children are different from one another. Results indicate that standardizing the anatomic point for the WC measurements is necessary.


The diamagnetic component map from quantitative susceptibility mapping (QSM) source separation reveals pathological alteration in Alzheimer's disease-driven neurodegeneration.
A sensitive and accurate imaging technique capable of tracking the disease progression of Alzheimer's Disease (AD) driven amnestic dementia would be beneficial. A currently available method for pathology detection in AD with high accuracy is Positron Emission Tomography (PET) imaging, despite certain limitations such as low spatial resolution, off-targeting error, and radiation exposure. Non-invasive MRI scanning with quantitative magnetic susceptibility measurements can be used as a complementary tool. To date, quantitative susceptibility mapping (QSM) has widely been used in tracking deep gray matter iron accumulation in AD. The present work proposes that by compartmentalizing quantitative susceptibility into paramagnetic and diamagnetic components, more holistic information about AD pathogenesis can be acquired. Particularly, diamagnetic component susceptibility (DCS) can be a powerful indicator for tracking protein accumulation in the gray matter (GM), demyelination in the white matter (WM), and relevant changes in the cerebrospinal fluid (CSF). In the current work, voxel-wise group analysis of the WM and the CSF regions show significantly lower |DCS| (the absolute value of DCS) value for amnestic dementia patients compared to healthy controls. Additionally, |DCS| and τ PET standardized uptake value ratio (SUVr) were found to be associated in several GM regions typically affected by τ deposition in AD. Therefore, we propose that the separated diamagnetic susceptibility can be used to track pathological neurodegeneration in different tissue types and regions of the brain. With the initial evidence, we believe the usage of compartmentalized susceptibility demonstrates substantive potential as an MRI-based technique for tracking AD-driven neurodegeneration.


Nerve gas-induced seizures: role of acetylcholine in the rapid induction of Fos and glial fibrillary acidic protein in piriform cortex.
Soman (pinacolymethylphosphonofluoridate), a highly potent irreversible inhibitor of acetylcholinesterase (AChE), causes seizures and rapidly increases Fos and glial fibrillary acidic protein (GFAP) staining in piriform cortex (PC). This suggests that the inhibition of AChE by soman leads to increased acetylcholine (ACh) and neuronal excitability in PC. The sole source of cholinergic input to PC is from the nucleus of the diagonal band (NDB). To investigate the role of ACh in soman-induced seizures, we lesioned cholinergic neurons in NDB unilaterally with 192-IgG-saporin. By 10 d, saporin eliminated staining for choline acetyltransferase (ChAT), the synthetic enzyme for ACh, in NDB ipsilateral to the lesion. Staining for AChE, the degradative enzyme for ACh, was eliminated in PC ipsilateral to the lesioned NDB. By 45-60 min after soman, increased Fos and GFAP staining in PC was evident only ipsilateral to the unlesioned NDB. By 90-120 min after soman, Fos and GFAP staining increased bilaterally in PC. In a second experiment, electrical stimulation electrodes were implanted unilaterally in the NDB to activate focally the projections to PC in unanesthetized rats. Within 5 min of NDB stimulation, there were clear behavioral and EEG signs of convulsions. After 45-60 min of NDB stimulation, there was increased Fos and GFAP staining in layer II of PC ipsilateral to the stimulation site. Pretreatment with the selective muscarinic receptor antagonist scopolamine blocked the convulsions and prevented increased Fos and GFAP staining in PC. These results suggest that ACh release in PC triggers the initiation of seizures and gliosis after soman administration, predominantly by the activation of muscarinic receptors.