[Epidemiological study on the incidence of chronic lymphocytic thyroiditis in childhood (author's transl)].
An epidemiological survey on the incidence of chronic lymphocytic thyroiditis in childhood was performed in 11,353 apparently healthy school children in Chiba prefecture, Japan. The present study included 9,416 school children (4,401 boys and 5,015 girls, ages 6--18 yrs) in Chiba City and 1,937 children (744 boys and 1,193 girls, ages 16-18 yrs) in Tateyama City. The first group was selected as a representative of urban area, and the second group was selected as that of seaside area. Children having goiter were selected for testing antihyroblobulin and antimicrosomal antibodies in sera. Final diagnosis of chronic lymphocytic thyroiditis was based on histological specimens obtained by needle biopsies on the antithyroid antibody positive subjects. The overall incidence of chronic lymphocytic thyroiditis in these children with 1.7 per 1,000 children. There was a considerable sex difference in the prevalence. None of the patients were boys. In girls the incidence increased with age: ages 6-12 0.9, ages 13-15 4.6 and ages 16-18 3.1-4.2 per 1,000, respectively. The incidence in the seaside area, 2.6 per 1,000 was not significantly higher than that in the urban area, 1.8 per 1,000. Histologically, all cases were classified as focal thyroiditis.


Is the matching familiar figures test a measure of cognitive style? A warning for users.
A probabilistic model of reflection-impulsivity as measured by the Matching Familiar Figures Test (MFFT) is presented and tested on 77 fourth graders. In testing the model two groups emerged, a random response group (n = 22) and a cognitive response group (n = 55), who use the evaluation process. Correlations among latencies, total errors, initial errors, school-scores, and IQs were compared for our total sample and the two groups. The correlation of MFFT latencies and errors disappeared for the random-response group and new correlations with errors appeared while the cognitive response group kept a statistically significant correlation of latencies with errors and no other error correlation was shown. This last group was classified by Kagan's median-split procedure showing that most reflective subjects kept their classification. Preliminary results suggest a reinterpretation of reflection-impulsivity literature, especially as related to the impulsive style.


Delayed protection by ESAT-6-specific effector CD4+ T cells after airborne M. tuberculosis infection.
Mycobacterium tuberculosis infection induces complex CD4 T cell responses that include T helper type 1 (Th1) cells and regulatory T cells. Although Th1 cells control infection, they are unable to fully eliminate M. tuberculosis, suggesting that Th1-mediated immunity is restrained from its full sterilizing potential. Investigation into T cell-mediated defense is hindered by difficulties in expanding M. tuberculosis-specific T cells. To circumvent this problem, we cloned CD4(+) T cells from M. tuberculosis-infected B6 mice and generated transgenic mice expressing a T cell receptor specific for the immunodominant antigen early secreted antigenic target 6 (ESAT-6). Adoptively transferred naive ESAT-6-specific CD4(+) T cells are activated in pulmonary lymph nodes between 7 and 10 d after aerosol infection and undergo robust expansion before trafficking to the lung. Adoptive transfer of activated ESAT-6-specific Th1 cells into naive recipients before aerosol M. tuberculosis infection dramatically enhances resistance, resulting in 100-fold fewer bacteria in infected lungs. However, despite large numbers of Th1 cells in the lungs of mice at the time of M. tuberculosis challenge, protection was not manifested until after 7 d following infection. Our results demonstrate that pathogen-specific Th1 cells can provide protection against inhaled M. tuberculosis, but only after the first week of infection.


Expression of a single gene produces both forms of skeletal muscle cyclic nucleotide-gated channels.
Cyclic nucleotide-gated cation channels in skeletal muscle are responsible for insulin-activated sodium entry into this tissue (J. E. M. McGeoch and G. Guidotti. J. Biol. Chem. 267: 832-841, 1992). These channels have previously been isolated from rabbit skeletal muscle by 8-bromoguanosine 3',5'-cyclic monophosphate (8-BrcGMP) affinity chromatography, which separates them into two populations differing in nucleotide affinity [L. C. Santy and G. Guidotti. Am. J. Physiol. 271 (Endocrinol. Metab. 34): E1051-E1060, 1996]. In this study, a polymerase chain reaction approach was used to identify skeletal muscle cyclic nucleotide-gated channel cDNAs. Rabbit skeletal muscle expresses the same cyclic nucleotide-gated channel as rabbit aorta (M. Biel, W. Altenhofen, R. Hullin, J. Ludwig, M. Freichel, V. Flockerzi, N. Dascal, U. B. Kaupp, and F. Hofmann. FEBS Lett. 329: 134-138, 1993). The entire cDNA for this gene was cloned from rabbit skeletal muscle and an antiserum to this protein produced. Expression of this cDNA produces a 63-kDa protein with cyclic nucleotide-gated channel activity. A similarly sized immunoreactive protein is present in sarcolemma. Purification of the expressed channels reveals that this single gene produces both native skeletal muscle channel populations.


Experimental tests for heritable morphological color plasticity in non-native brown trout (Salmo trutta) populations.
The success of invasive species is frequently attributed to phenotypic plasticity, which facilitates persistence in novel environments. Here we report on experimental tests to determine whether the intensity of cryptic coloration patterns in a global invader (brown trout, Salmo trutta) was primarily the result of plasticity or heritable variation. Juvenile F1 offspring were created through experimental crosses of wild-caught parents and reared for 30 days in the laboratory in a split-brood design on either light or dark-colored gravel substrate. Skin and fin coloration quantified with digital photography and image analysis indicated strong plastic effects in response to substrate color; individuals reared on dark substrate had both darker melanin-based skin color and carotenoid-based fin colors than other members of their population reared on light substrate. Slopes of skin and fin color reaction norms were parallel between environments, which is not consistent with heritable population-level plasticity to substrate color. Similarly, we observed weak differences in population-level color within an environment, again suggesting little genetic control on the intensity of skin and fin colors. Taken as whole, our results are consistent with the hypothesis that phenotypic plasticity may have facilitated the success of brown trout invasions and suggests that plasticity is the most likely explanation for the variation in color intensity observed among these populations in nature.


Validation of mathematical models for the prediction of organs-at-risk dosimetric metrics in high-dose-rate gynecologic interstitial brachytherapy.
Given the complicated nature of an interstitial gynecologic brachytherapy treatment plan, the use of a quantitative tool to evaluate the quality of the achieved metrics compared to clinical practice would be advantageous. For this purpose, predictive mathematical models to predict the D2cc of rectum and bladder in interstitial gynecologic brachytherapy are discussed and validated. Previous plans were used to establish the relationship between D2cc and the overlapping volume of the organ at risk with the targeted area (C0) or a 1-cm expansion of the target area (C1). Three mathematical models were evaluated: D2cc = α*C1 + β (LIN); D2cc = α - exp(-β*C0) (EXP); and a mixed approach (MIX), where both C0 and C1 were inputs of the model. The parameters of the models were optimized on a training set of patient data, and the predictive error of each model (predicted D2cc - real D2cc) was calculated on a validation set of patient data. The data of 20 patients were used to perform a K-fold cross validation analysis, with K = 2, 4, 6, 8, 10, and 20. MIX was associated with the smallest mean prediction error <6.4% for an 18-patient training set; LIN had an error <8.5%; EXP had an error <8.3%. Best case scenario analysis shows that an error ≤ 5% can be achieved for a ten-patient training set with MIX, an error ≤ 7.4% for LIN, and an error ≤ 6.9% for EXP. The error decreases with the increase in training set size, with the most marked decrease observed for MIX. The MIX model can predict the D2cc of the organs at risk with an error lower than 5% with a training set of ten patients or greater. The model can be used in the development of quality assurance tools to identify treatment plans with suboptimal sparing of the organs at risk. It can also be used to improve preplanning and in the development of real-time intraoperative planning tools.


An unexpected non-conjugated AIEgen with a discrete dimer for pure intermolecular through-space charge transfer emission.
Manipulation of the charge transfer in donor-acceptor-type molecules is essential for the design of controllable aggregate luminescent materials. Apart from the traditional through-bond charge transfer (TBCT) systems which suffer from complicated structural design, poor tunability and low quantum efficiency, through-space charge transfer (TSCT) has been proved as an alternative yet facile strategy in tuning photophysical processes. In this work, by simply changing nucleophilic reaction bases, a traditional conjugated acrylonitrile AP1 and an unexpected non-conjugated AP2 with a carboxamide-functionalized oxirane linker could be obtained. The long-range π-π stacking in conjugated AP1 results in mixed intramolecular TBCT plus intermolecular TSCT emission. However, facilitated by the steric hindrance effect of the big oxirane connector and the unique discrete dimer packing, non-conjugated AP2 exhibits pure and efficient intermolecular TSCT emission in both aggregate and crystalline states. The flexibility of the non-conjugated character further leads to better reversible stimuli-responsiveness to mechanical force for AP2 than for the rigid AP1.


Electron Beam Etching of CaO Crystals Observed Atom by Atom.
With the rapid development of nanoscale structuring technology, the precision in the etching reaches the sub-10 nm scale today. However, with the ongoing development of nanofabrication the etching mechanisms with atomic precision still have to be understood in detail and improved. Here we observe, atom by atom, how preferential facets form in CaO crystals that are etched by an electron beam in an in situ high-resolution transmission electron microscope (HRTEM). An etching mechanism under electron beam irradiation is observed that is surprisingly similar to chemical etching and results in the formation of nanofacets. The observations also explain the dynamics of surface roughening. Our findings show how electron beam etching technology can be developed to ultimately realize tailoring of the facets of various crystalline materials with atomic precision.


Suspected bacterial endophthalmitis following intravitreal anti-VEGF injection: case series and literature review.
To report an up-to-date overview of all patients reported in the literature with suspected bacterial endophthalmitis following anti-VEGF injection. Secondly, to identify specific symptoms and signs to differentiate between infectious and noninfectious endophthalmitis. A Pubmed search retrieved 12 retrospective case series which had included a total of 118 patients with suspected bacterial endophthalmitis after anti-VEGF injection. Data of 15 patients from the Rotterdam Eye Hospital were added. Patients were divided into three groups: those who did not receive intravitreal antibiotics (group A), patients who received intravitreal antibiotics with biopsy-negative cultures (group B) and those with biopsy-positive cultures (group C). The median time between anti-VEGF injection and presentation with suspected bacterial endophthalmitis was 1 day in group A compared to 3 days in groups B and C. At presentation, patients of group A had a better median visual acuity (logMAR 1.0) compared to those in groups B and C (logMAR 2.1 and 2.5, respectively). This study suggests that patients presenting with a visual acuity of 20/200 (logMAR 1.0) or less and later than 24 h after injection are more likely to have bacterial endophthalmitis. To prevent undertreatment in these patients, the threshold to proceed to vitreous biopsy and empirical intravitreous antibiotics should be low.


Anthropometric, body composition, and somatotype characteristics of Japanese young women: Implications for normal-weight obesity syndrome and sarcopenia diagnosis criteria.
The purpose of this study was to examine the anthropometric, body composition, and somatotype characteristics of Japanese young women and to focus on normal-weight obesity syndrome and sarcopenia diagnosis criteria. A total of 124 Japanese university freshmen women were measured at body mass index (BMI), percent body fat and skeletal muscle index (SMI), usual gait test, and handgrip strength. The subjects were divided into obesity (≥30% body fat; BMI: ≥25.0 kg/m2), normal-weight obesity (≥30% body fat; BMI: 18.5-24.9 kg/m2), sarcopenia (handgrip, <18 kg; gait speed: ≤0.8 m/s; SMI: <5.7 kg/m2), or presarcopenia (SMI: <5.7 kg/m2). There were no subjects below the sarcopenia diagnosis criteria in usual gait speed, but not for handgrip (0.8%) and SMI (36.3%). The prevalence of presarcopenia group (36.3%) is higher than in the normal-weight obesity (16.9%) and obesity (4.8%) groups. Anthropometry and sarcopenia diagnosis assessments were significantly higher in normal-weight obesity and standard groups compared with presarcopenia group. The number of young women was higher in the presarcopenia group than in the normal-weight obesity group, suggesting that the improvement of intrinsic skeletal muscle mass rather than fat mass is important for Japanese young women.


[Hepatoprotective effect of prostaglandins].
The review deals with the data on the hepatoprotective effect of prostaglandins in experimental toxic and immune hepatitides, ischemia and partial resection of the liver. It also discusses the use of prostaglandins in the clinic in hepatic insufficiency and transplantation of the liver.


Methicillin-resistant Staphylococcus aureus in surgical patients: Malaysian experience.
Methicillin-resistant Staphylococcus aureus has emerged as an important cause of nosocomial infections in recent years. During 1988 in the Department of Surgery of the University Hospital in Kuala Lumpur, Malaysia, 148 patients were shown to be infected or colonized with these organisms. The patients at risk were those who stay in hospital for greater than 14 days, those over 50 years of age, patients who underwent neurosurgery, cardiothoracic surgery, or were admitted with major burns. Of the 148 patients, 78 (52.7%) were clinically infected, the remaining 70 being colonized. A total of 28 patients died (18.9%) but only five (3.4%) as a direct result of this infection. The estimated annual cost of controlling the organism was found to be approximately MR$250,000. (50,000 pounds). This nosocomial infection therefore represents a serious problem, especially in developing countries where health funding and health facilities are limited.


Direct in Vivo Electrochemical Detection of Resting Dopamine Using Poly(3,4-ethylenedioxythiophene)/Carbon Nanotube Functionalized Microelectrodes.
Dopamine (DA) is a monoamine neurotransmitter responsible for the maintenance of a variety of vital life functions. In vivo DA signaling occurs over multiple time scales, from subsecond phasic release due to dopamine neuron firing to tonic release responsible for long-term DA concentration changes over minutes to hours. Due to the complex, multifaceted nature of DA signaling, analytical sensing technology must be capable of recording DA from multiple locations and over multiple time scales. Decades of research has focused on improving in vivo detection capabilities for subsecond phasic DA, but the accurate detection of absolute resting DA levels in real time has proven challenging. We have developed a poly(3,4-ethylenedioxythiophene) (PEDOT)-based nanocomposite coating that exhibits excellent DA sensing capabilities for resting DA. PEDOT/functionalized carbon nanotube (PEDOT/CNT)-coated carbon fiber microelectrodes (CFEs) are capable of directly measuring resting DA using square wave voltammetry (SWV) with high sensitivity and selectivity. Incorporation of a PEDOT/CNT coating significantly increases the sensitivity for the detection of resting DA by a factor of 422. SWV measurements performed at PEDOT/CNT-functionalized CFEs implanted in the rat dorsal striatum reveal the absolute basal DA concentration to be 82 ± 6 nM. Systemic administration of the dopamine transporter inhibitor nomifensine increases resting DA to a maximum 207 ± 16 nM at 28 ± 2 min following injection. PEDOT/CNT was also functionalized onto individual gold electrode sites along silicon microelectrode arrays (MEAs) to produce a multisite DA sensing electrode. MEA implantation allows for the quantification of basal DA from different brain regions with excellent spatial resolution. SWV detection paired with PEDOT/CNT functionalization is highly adaptable and shows great promise for tonic DA detection with high spatial and temporal resolution.


Hypothyroidism and reversible kidney dysfunction: an essential relationship to recognize.
To report 3 cases of reversible hypothyroidism-induced kidney dysfunction and review the interaction between these commonly encountered, yet seemingly disparate, conditions. We describe the clinical course and laboratory and physical findings of 3 patients who presented with kidney dysfunction that improved after initiating thyroid hormone replacement therapy. We also review similar cases in the literature and discuss the pathophysiologic mechanisms. A 68-year-old male presented with classical signs and symptoms of hypothyroidism, including fatigue, confusion, and gait imbalance. Physical exam showed bradycardia, thyromegaly, slow mentation, and cracked, thin skin; he was found to have decreased kidney function. Second, a 42-year-old previously healthy female presented with bilateral hand swelling and elevated serum creatinine with an otherwise unremarkable physical exam. The third patient was a 72-year-old male with advanced heart failure on amiodarone and stage 3 chronic kidney disease who presented with fatigue, acute kidney injury, and lower extremity edema. In all cases, serum creatinine and thyroid-stimulating hormone (TSH) were elevated at presentation (1.4-3.0 mg/dL and 94.1-184 mIU/L respectively), and free thyroxine (T4) was low (undetectable-0.4 ng/dL). The initiation or increased dose of levothyroxine normalized serum creatinine to baseline within 2 to 10 months. Hypothyroidism and kidney dysfunction are both commonly encountered clinical entities, but the interplay between the thyroid gland and kidneys may be infrequently recalled, causing the reversible relationship between these 2 disorders to be missed.


Alcoholic liver disease: treatment.
The excess consumption of alcohol is associated with alcoholic liver diseases (ALD). ALD is a major healthcare problem, personal and social burden, and significant reason for economic loss worldwide. The ALD spectrum includes alcoholic fatty liver, alcoholic hepatitis, cirrhosis, and the development of hepatocellular carcinoma. The diagnosis of ALD is based on a combination of clinical features, including a history of significant alcohol intake, evidence of liver disease, and laboratory findings. Abstinence is the most important treatment for ALD and the treatment plan varies according to the stage of the disease. Various treatments including abstinence, nutritional therapy, pharmacological therapy, psychotherapy, and surgery are currently available. For severe alcoholic hepatitis, corticosteroid or pentoxifylline are recommended based on the guidelines. In addition, new therapeutic targets are being under investigation.


Identity and Relational Factors Associated with Sexual Role and Positioning for Anal Sex among Colombian Sexual Minority Men.
This study aimed to identify Top, Bottom, and Versatile sexual role identities and anal sex behavior profiles using latent class analysis in a sample of 942 sexual minority men living in Bogotá. A Versatile-insertive and receptive class (52.2%) was the most prevalent of the four resulting classes, whereas the least common was a class (1.7%) that did not use labels and had a low probability of anal sex. We examined whether identity and relational factors (i.e., sexual orientation, LGBT collective identity, and partner type) were associated with profiles. Gay identity was associated with versatile and receptive classes and bisexual identity was associated with insertive and versatile classes. LGBT collective identity was associated with the class characterized by Bottom identity and receptive positioning. Partner type was not associated with class membership, but versatile behaviors were more common among encounters with a main partner. Models using data at different timescales offered consistent patterns of behavior between the last encounter and the past three months, though the versatile class in the three-month model split into two classes based on frequency of versatile positioning. Findings highlight the relationship between sexual identity and positioning and can inform interventions for sexual health education and identity development.


Nuclear export of the DEAD box An3 protein by CRM1 is coupled to An3 helicase activity.
We have recently identified the Xenopus laevis An3 protein as a bona fide substrate for the nuclear export receptor CRM1 (Exportin 1). An3 binds directly to CRM1 with high affinity via a leucine-rich nuclear export signal located in the extreme N terminus. An3 is a member of the DEAD box family of RNA helicases, which unwind RNA duplexes. RNA unwinding is coupled to hydrolysis of nucleoside triphosphates by the helicase, and the ATPase activity of several helicases is greatly stimulated by various polynucleotides. Here we report that dATP hydrolysis by An3 is stimulated approximately 6-fold by total RNA from X. laevis oocytes, whereas poly(U) RNA fails to enhance hydrolysis, suggesting the existence of a specific RNA activator for An3. Kinetic analysis reveals that a mutation within the conserved DEAD box motif reduces the rate of dATP hydrolysis by approximately 6-fold. In accordance with this, the DEAD box mutant is unable to unwind double-stranded RNA. Microinjection of the An3 DEAD box mutant into X. laevis oocytes nuclei reveals a significantly lower export rate as compared with wild-type An3 protein. This is not because the mutant has lower affinity toward CRM1, nor is it due to altered RNA binding capacity. This suggests that nuclear export of An3 protein by CRM1 is coupled to An3 helicase activity.


[Leg ulcers are rare in Tunisian women].
Numerous reports from Tunisia and Morocco have underlined the low frequency of leg ulcers in women from the Maghreb region in comparison with European women. This retrospective study describes patients hospitalized for leg ulcers in the Dermatology Department of Charles Nicolle Hospital in Tunis between January 1995 and December 2005. A total of 134 patients including 107 men and 27 women (M/F sex-ratio: 3.96) were hospitalized for leg ulcers. Venous leg ulcer was the most common accounting for 54.5% of cases overall, 57% of cases in men and 33.3% of cases in women (p = 0.028).


Folic acid supplement use in the prevention of neural tube defects.
In 2008, planned folic acid fortification for the prevention of Neural Tube Defects (NTD) was postponed. Concurrently, the economic recession may have affected dietary folic acid intake, placing increased emphasis on supplement use. This study examined folic acid supplement use in 2009. A cross-sectional survey of 300 ante-natal women was undertaken to assess folic acid knowledge and use. Associations between demographic, obstetric variables and folic acid knowledge and use were examined. A majority, 284/297 (96%), had heard of folic acid, and 178/297 (60%) knew that it could prevent NTD. Most, 270/297 (91%) had taken it during their pregnancy, but only 107/297 (36%) had used it periconceptionally. Being older, married, planned pregnancy and better socioeconomic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from economic status were associated with periconceptional use. Periconceptional folic acid use in 2009 was very low, little changed from earlier years. Continuous promotion efforts are necessary. Close monitoring of folic acid intake and NTD rates is essential, particularly in the absence of fortification.


Drafting the Aboriginal and Islander Mental Health Initiative for Youth (AIMhi-Y) App: Results of a formative mixed methods study.
Culturally responsive, strengths-based early-intervention mental health treatment programs are considered most appropriate to influence the high rates of psychological distress and suicide experienced by Aboriginal and Torres Strait Islander youth. Few early intervention services effectively bridge the socio-cultural and geographic challenges of providing sufficient and culturally relevant services in rural and remote Australia. Mental Health apps provide an opportunity to bridge current gaps in service access if co-designed with Aboriginal and Torres Strait Islander youth to meet their needs. This paper reports the results of the formative stage of the AIMhi-Y App development process which engaged Aboriginal and Torres Strait Islander youth in the co-design of the new culturally informed AIMhi-Y App. Using a participatory design research approach, a series of co-design workshops were held across three sites with five groups of young people. Workshops explored concepts, understanding, language, acceptability of electronic mental health tools (e-mental health) and identified important characteristics of the presented applications and websites, chosen for relevance to this group. An additional peer supported online survey explored use of technology, help seeking and e-mental health design elements which contribute to acceptability. Forty-five, Aboriginal and Torres Strait Islander youth, aged 10-18 years, from three sites in the Northern Territory (NT) were involved in the workshops (n = 29). Although experiencing psychological distress, participants faced barriers to help seeking. Apps were perceived as a potential solution to overcome barriers by increasing mental health literacy, providing anonymity if desired, and linking young people with further help. Preferred app characteristics included a strength-based approach, mental health information, relatable content and a fun, appealing, easy to use interface which encouraged app progression. Findings informed the new AIMhi-Y App draft, which is a strengths-based early intervention wellbeing app for Aboriginal and Torres Strait Islander youth. Research findings highlight the need, feasibility and potential of these types of tools, from the perspective of Aboriginal and Torres Strait Islander youth.


Systemic diseases caused by oral infection.
Recently, it has been recognized that oral infection, especially periodontitis, may affect the course and pathogenesis of a number of systemic diseases, such as cardiovascular disease, bacterial pneumonia, diabetes mellitus, and low birth weight. The purpose of this review is to evaluate the current status of oral infections, especially periodontitis, as a causal factor for systemic diseases. Three mechanisms or pathways linking oral infections to secondary systemic effects have been proposed: (i) metastatic spread of infection from the oral cavity as a result of transient bacteremia, (ii) metastatic injury from the effects of circulating oral microbial toxins, and (iii) metastatic inflammation caused by immunological injury induced by oral microorganisms. Periodontitis as a major oral infection may affect the host's susceptibility to systemic disease in three ways: by shared risk factors; subgingival biofilms acting as reservoirs of gram-negative bacteria; and the periodontium acting as a reservoir of inflammatory mediators. Proposed evidence and mechanisms of the above odontogenic systemic diseases are given.


A Wearable Force Myography-Based Armband for Recognition of Upper Limb Gestures.
Force myography (FMG) represents a promising alternative to surface electromyography (EMG) in the context of controlling bio-robotic hands. In this study, we built upon our prior research by introducing a novel wearable armband based on FMG technology, which integrates force-sensitive resistor (FSR) sensors housed in newly designed casings. We evaluated the sensors' characteristics, including their load-voltage relationship and signal stability during the execution of gestures over time. Two sensor arrangements were evaluated: arrangement A, featuring sensors spaced at 4.5 cm intervals, and arrangement B, with sensors distributed evenly along the forearm. The data collection involved six participants, including three individuals with trans-radial amputations, who performed nine upper limb gestures. The prediction performance was assessed using support vector machines (SVMs) and k-nearest neighbor (KNN) algorithms for both sensor arrangments. The results revealed that the developed sensor exhibited non-linear behavior, and its sensitivity varied with the applied force. Notably, arrangement B outperformed arrangement A in classifying the nine gestures, with an average accuracy of 95.4 ± 2.1% compared to arrangement A's 91.3 ± 2.3%. The utilization of the arrangement B armband led to a substantial increase in the average prediction accuracy, demonstrating an improvement of up to 4.5%.


Labeling of mesenchymal stem cells for MRI with single-cell sensitivity.
Sensitive cell detection by magnetic resonance imaging (MRI) is an important tool for the development of cell therapies. However, clinically approved contrast agents that allow single-cell detection are currently not available. Therefore, we compared very small iron oxide nanoparticles (VSOP) and new multicore carboxymethyl dextran-coated iron oxide nanoparticles (multicore particles, MCP) designed by our department for magnetic particle imaging (MPI) with discontinued Resovist(®) regarding their suitability for detection of single mesenchymal stem cells (MSC) by MRI. We achieved an average intracellular nanoparticle (NP) load of >10 pg Fe per cell without the use of transfection agents. NP loading did not lead to significantly different results in proliferation, colony formation, and multilineage in vitro differentiation assays in comparison to controls. MRI allowed single-cell detection using VSOP, MCP, and Resovist(®) in conjunction with high-resolution T2*-weighted imaging at 7 T with postprocessing of phase images in agarose cell phantoms and in vivo after delivery of 2,000 NP-labeled MSC into mouse brains via the left carotid artery. With optimized labeling conditions, a detection rate of ~45% was achieved; however, the experiments were limited by nonhomogeneous NP loading of the MSC population. Attempts should be made to achieve better cell separation for homogeneous NP loading and to thus improve NP-uptake-dependent biocompatibility studies and cell detection by MRI and future MPI. Additionally, using a 7 T MR imager equipped with a cryocoil resulted in approximately two times higher detection. In conclusion, we established labeling conditions for new high-relaxivity MCP, VSOP, and Resovist(®) for improved MRI of MSC with single-cell sensitivity.


Raw soybeans for gestating swine.
An experiment was conducted to determine the influence of feeding ground raw soybeans to swine during gestation on reproductive performance for three consecutive parities. Sixty crossbred gilts were bred and randomly assigned to two dietary treatments with 30 gilts/treatment. The diets were formulated to contain 14% crude protein with either soybean meal (SBM) or raw soybeans (RSB) serving as the source of supplemental protein. All animals were fed in individual gestation stalls and were given 1.81 kg of feed/d. Upon entering the farrowing house at approximately 110 d of gestation, all animals, regardless of previous treatment, were fed the same lactation diet (15% protein corn-soybean meal diet) until the pigs were weaned (28 d). After completing three parities, 88 of a possible 90 litters were farrowed by each dietary group. Total number of live pigs at parturition and 21 d for three parities were: (SBM) 887, 732 and (RSB) 924, 765, respectively. Average pig birth and 21-d weights for each dietary group were (SBM) 1.52, 5.42 and (RSB) 1.59, 5.41 kg, respectively. Pigs from dams fed RSB had higher average pig birth weights (P less than .05), but weaning weights were not affected. There were no significant differences in maternal weight changes during gestation. Milk samples were collected within 6 h after parturition, 3 and 14 d of lactation. Percentage milk fat for each time period was: (SBM) 5.6, 9.0, 7.0 and (RSB) 6.3, 10.7, 6.5, respectively. Sows fed RSB had a higher milk fat at 3 d (P less than .05) but a lower milk fat at 14 d (P less than .1) than did the sows fed SBM. The study indicated RSB can be effectively utilized in gestation diets fed to swine.


Salivary Total Antioxidant and Lipid Peroxidation Levels in Passive Smoking and Nonsmoking Adolescents.
Environmental tobacco smoke (ETS) is one of the most toxic environmental exposures and passive smoking is an important general health problem. Children are the most vulnerable group to ETS exposure. This study aimed to compare the salivary total antioxidant capacity (TAC) and lipid peroxidation levels in passive smoking and nonsmoking adolescents aged 12-15 years. This descriptive-analytical study was conducted on 80 adolescents aged 12-15 years. The case group included passive smokers and the control group comprised nonsmokers. These groups were age- and sex-matched ones. Unstimulated saliva of both groups was collected using the spitting method. Then, the salivary total antioxidant and lipid peroxidation levels were measured using the ferric-reducing antioxidant power (FRAP) and thiobarbituric acid reactive substances (TBARS) assays, respectively. The independent samples t-test was used for data comparison. There was a significant difference in salivary total antioxidant levels between the case group (51.98 ± 88.97 µM) and the control group (174.35 ± 148.15 µM) (P = 0.003). There was no significant difference between the case group (0.97 ± 1.96) and the control group (0.81 ± 0.97) in lipid peroxidation levels (P = 0.542). It seems that passive smoking can reduce the salivary TAC of adolescents, thereby threatening oral cavity health.


Priming of courageous behavior: contrast effects in spider fearful women.
Recently, researchers have called for therapeutic applications of behavioral primes (Shalev & Bargh, 2011). We evaluated whether courageous approach behavior might be facilitated through priming in a sample of spider fearful women. Undergraduate student women reporting elevated spider fear (N = 33, Age mean = 18.88) were recruited for this study. Participants completed self-report measures of spider fear and dispositional courage. They then completed either a courage or neutral word search prime, which was followed by a behavioral approach task involving a tarantula. Consistent with predictions, among those reporting lower dispositional courage, the courage prime led to reduced approach behavior relative to the neutral prime. However, no group differences were found among those high in dispositional courage. These findings point to the importance of self-perceptions in moderating the effects of behavioral primes and suggest limitations to the use of such interventions with individuals with psychological dysfunction.


Charting a Course: Navigating Rigor and Meaning in Global Health Research.
In the rapidly evolving landscape of global health research, the tension between scientific rigor and contextual meaning presents a critical challenge. Drawing on our work with the Global Diet and Physical Activity Network, this commentary explores the complexities of conducting environmental audits for physical activity and diet in 4 rapidly urbanizing African cities: Yaoundé, Lagos, Cape Town, and Soweto. We illustrate the competing demands and tensions that researchers face in balancing rigor and meaning. We discuss the adaptation of internationally validated audit tools to local contexts and the importance of area-level deprivation in interpreting data. We also examine the feasibility of virtual assessment tools, emphasizing the value of local expertise. We argue for a balanced approach that marries research rigor with contextual meaning, advocating for transparency, humility, and meaningful community engagement.


In vitro analysis of polypeptide requirements of multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600.
An in vitro study of the multicomponent phenol hydroxylase from Pseudomonas sp. strain CF600 was performed. Phenol-stimulated oxygen uptake from crude extracts was strictly dependent on the addition of NAD(P)H and Fe2+ to assay mixtures. Five of six polypeptides required for growth on phenol were necessary for in vitro activity. One of the polypeptides was purified to homogeneity and found to be a flavin adenine dinucleotide containing iron-sulfur protein with significant sequence homology, at the amino terminus, to plant-type ferredoxins. This component, as in other oxygenase systems, probably functions to transfer electrons from NAD(P)H to the iron-requiring oxygenase component. Phenol hydroxylase from this organism is thus markedly different from bacterial flavoprotein monooxygenases commonly used for hydroxylation of other phenolic compounds, but bears a number of similarities to multicomponent oxygenase systems for unactivated compounds.


Finding primary targets of transcriptional regulators.
Transcriptional regulators directly regulate the transcription of primary target genes by occupying genomic response elements proximal to the target promoters. In turn, regulation of primary target genes triggers subsequent physiological events by acting on distinct biological pathways and modulating the expression of secondary target genes. Thus, distinguishing primary and secondary target genes is critical for our understanding of mechanisms underlying the biological effects of a regulator. In this article, four distinct strategies for identification of primary target genes are compared and discussed: bioinformatic approaches, ChIP on chip, and two novel strategies, ChIP scanning and in vitro genomic selection. Overall, these approaches complement each other, and depending on available information and resources, the appropriate methods can be chosen to identify primary target genes for a particular regulator.


Expression of a cloned K88ac adhesion antigen determinant: identification of a new adhesion cistron and role of a vector-encoded promoter.
The determinant for the K88ac adherence antigen of porcine enterotoxigenic Escherichia coli has been cloned previously onto the vector plasmid pBR322 to form the K88ac-pBR322 hybrid plasmid pMK005 (M. Kehoe et al., Nature [London] 291:122-126). Further studies on the expression of the K88ac antigen from pMK005 are presented in this paper. Expression was found to be dependent mainly on the P1 promoter of the pBR322 vector. The natural K88ac promoter was apparently not cloned from the original parental K88ac plasmid. The P1 promoter was deleted and replaced by a DNA sequence encoding the promoter-operator region of the E. coli tryptophan (Trp) operon. Cells harboring the Trp-pMK005 hybrid plasmid expressed high levels of K88ac antigen when the Trp promoter was repressed. If the promoter was derepressed either by growing the cells in low concentrations of tryptophan or in the presence of indole acrylic acid, growth of the cells harboring the Trp-pMK005 hybrid plasmid was inhibited. A quantitative assay was used to measure the levels of K88ac antigen expressed by cells harboring different pMK005::Tn5 plasmids. All cells were found to express a reduced level of K88ac antigen, providing evidence that a single transcription unit, initiating at promoter P1 of pBR322, may be involved in the expression of the K88ac antigen. By constructing specific deletion and insertion mutants of pMK005, a fifth adhesion cistron, tentatively named adhE, was identified and mapped at the proximal end of the K88ac determinant. Although the cistron is required for high-level expression of K88ac surface-associated fimbriae, as yet no gene product has been assigned to adhE.


Postnatal High Protein Intake Can Contribute to Accelerated Weight Gain of Infants and Increased Obesity Risk.
Worldwide, 38% of women are now overweight (BMI 25-30) or obese (BMI ≥30). There is increasing evidence that maternal obesity can result in unfavorable (epigenetic) pre- and postnatal programming of important genes of the offspring. Infants of overweight mothers show faster weight gain during infancy, which is associated with higher risk of obesity during childhood and adult life. This can have lifelong consequences such as increased risk of noncommunicable diseases. Many studies indicate that infants of obese and nonobese mothers who were fed traditional (high-protein) formulas gain more rapidly weight than breastfed infants. An updated meta-analysis (n = 1,150) indicates that infants from four continents who were fed a whey-based, low-protein (1.8 g/100 kcal) formula with an essential amino-acid profile closer to breast milk grow in accordance with the World Health Organization (WHO) growth standard (0-4 months). A new experimental low-protein (1.61-1.65 g protein/100 kcal) formula for infants between 3 and 12 months of age was recently tested in two randomized clinical trials. One trial in the general US population indicates lower weight between 4 and 12 months of age in infants fed the low-protein formula when compared to infants on the high-protein formula (p = 0.031). Weight gain was not inferior to the WHO growth standards. Longitudinal analysis of odds ratios from 4 to 12 months of age showed a lower incidence of infants with weight >85th percentile in the low-protein group compared with the high-protein group (p = 0.015). In the second trial, which was conducted in Chile and included infants of mothers with BMI >25, infants fed the low-protein formula gained less weight between 4 and 12 months (p = 0.022) and until 24 months (p = 0.031) than the high-protein group. Weight gain was similar to the breastfed reference group. In both trials, biomarkers of protein metabolism (insulin-like growth factor-1 and C-peptide) of the low-protein groups were closer to breastfed infants than the respective biomarkers of the high-protein groups. Health economic analyses indicate that feeding low-protein formulas to nonbreastfed infants would result in cost savings for both the individual and the society. Preventive measures against childhood and adult obesity should include promotion of breastfeeding for 6 months or longer, and use of low-protein formulas in nonbreastfed infants.


Statistical review: frequently given comments.
From 2006 to 2014, I have carried out approximately 200 statistical reviews of manuscripts for ARD. My most frequent review comments concern the following: 1. Report how missing data were handled. 2. Limit the number of covariates in regression analyses. 3. Do not use stepwise selection of covariates. 4. Use analysis of covariance (ANCOVA) to adjust for baseline values in randomised controlled trials. 5. Do not use ANCOVA to adjust for baseline values in observational studies. 6. Dichotomising a continuous variable: a bad idea. 7. Student's t test is better than non-parametric tests. 8. Do not use Yates' continuity correction. 9. Mean (SD) is also relevant for non-normally distributed data. 10. Report estimate, CI and (possibly) p value-in that order of importance. 11. Post hoc power calculations-do not do it. 12. Do not test for baseline imbalances in a randomised controlled trial. 13. Report actual p values with 2 digits, maximum 3 decimals. 14. Format for reporting CIs.


Summer temperature dependency of larch budmoth outbreaks revealed by Alpine tree-ring isotope chronologies.
Larch budmoth (LBM, Zeiraphera diniana Gn.) outbreaks cause discernable physical alteration of cell growth in tree rings of host subalpine larch (Larix decidua Mill.) in the European Alps. However, it is not clear if these outbreaks also impact isotopic signatures in tree-ring cellulose, thereby masking climatic signals. We compared LBM outbreak events in stable carbon and oxygen isotope chronologies of larch and their corresponding tree-ring widths from two high-elevation sites (1800-2200 m a.s.l.) in the Swiss Alps for the period AD 1900-2004 against isotope data obtained from non-host spruce (Picea abies). At each site, two age classes of tree individuals (150-250 and 450-550 years old) were sampled. Inclusion of the latter age class enabled one chronology to be extended back to AD 1650, and a comparison with long-term monthly resolved temperature data. Within the constraints of this local study, we found that: (1) isotopic ratios in tree rings of larch provide a strong and consistent climatic signal of temperature; (2) at all sites the isotope signatures were not disturbed by LBM outbreaks, as shown, for example, by exceptionally high significant correlations between non-host spruce and host larch chronologies; (3) below-average July to August temperatures and LBM defoliation events have been coupled for more than three centuries. Dampening of Alps-wide LBM cyclicity since the 1980s and the coincidence of recently absent cool summers in the European Alps reinforce the assumption of a strong coherence between summer temperatures and LBM defoliation events. Our results demonstrate that stable isotopes in tree-ring cellulose of larch are an excellent climate proxy enabling the analysis of climate-driven changes of LBM cycles in the long term.


[Abdominal wall endometriosis. Case report and literature review].
Endometriosis, is a disorder affecting as many as 15% of women of childbearing age, is defined as the aberrant or heterotopic growth of glands and stroma identical to the lining uterus. Endometriosis, can be macroscopically identified generally confined to the pelvis, but it can proliferate in other areas like pleura, skin, extremities, lung, spleen, gallbladder, stomach, kidney and abdominal wall. Abdominal wall endometriosis usually occurs in the surgical scar of previous cesarean sections. This condition often looks like a cyclic abdominal pain with a palpable mass or tumor. We report a case of abdominal endometriosis. The definitive diagnosis was established by pathologic analysis.


Activation of the NRF2 antioxidant program sensitizes tumors to G6PD inhibition.
The KEAP1/NRF2 pathway promotes metabolic rewiring to support redox homeostasis. Activation of NRF2 occurs in many cancers, often due to KEAP1 mutations, and is associated with more aggressive disease and treatment resistance. To identify metabolic dependencies in cancers with NRF2 activation, we performed a metabolism-focused CRISPR screen. Glucose-6-phosphate dehydrogenase (G6PD), which was recently shown to be dispensable in Ras-driven tumors, was a top dependency. G6PD catalyzes the committed step of the oxidative pentose phosphate pathway that produces NADPH and nucleotide precursors, but neither antioxidants nor nucleosides rescued. Instead, G6PD loss triggered tricarboxylic acid (TCA) intermediate depletion because of up-regulation of the alternative NADPH-producing enzymes malic enzyme and isocitrate dehydrogenase. In vivo, G6PD impairment markedly suppressed KEAP1 mutant tumor growth, and this suppression was further augmented by TCA depletion by glutaminase inhibition. Thus, G6PD inhibition–induced TCA depletion is a therapeutic vulnerability of NRF2-activated cancer.


Molecular mechanisms underlying effects of neural stem cells against traumatic axonal injury.
Transplantation of neural stem cells (NSCs) improves functional outcomes following traumatic brain injury (TBI). Previously we demonstrated that human NSCs (hNSCs) via releasing glial cell line-derived neurotrophic factor (GDNF), preserved cognitive function in rats following parasagittal fluid percussion. However, the underlying mechanisms remain elusive. In this study, we report that NSC grafts significantly reduce TBI-induced axonal injury in the fimbria and other brain regions by blocking abnormal accumulation of amyloid precursor protein (APP). A preliminary mass spectrometry proteomics study revealed the opposite effects of TBI and NSCs on many of the cytoskeletal proteins in the CA3 region of the hippocampus, including α-smooth muscle actin (α-SMA), the main stress fiber component. Further, Western blot and immunostaining studies confirmed that TBI significantly increased the expression of α-SMA in hippocampal neurons, whereas NSC grafts counteracted the effect of TBI. In an in vitro model, rapid stretch injury significantly shortened lengths of axons and dendrites, increased the expression of both APP and α-SMA, and induced actin aggregation, effects offset by GDNF treatment. These GDNF protective effects were reversed by a GDNF-neutralizing antibody or a specific calcineurin inhibitor, and were mimicked by a specific Rho inhibitor. In summary, we demonstrate for the first time that hNSC grafts and treatment with GDNF acutely reduce traumatic axonal injury and promote neurite outgrowth. Possible mechanisms underlying GDNF-mediated neurite protection include balancing the activity of calcineurin, whereas GDNF-induced neurite outgrowth may result from the reduction of the abnormal α-SMA expression and actin aggregation via blocking Rho signals. Our study also suggests the necessity of further exploring the roles of α-SMA in the central nervous system (CNS), which may lead to a new avenue to facilitate recovery after TBI and other injuries.


Do we know the answers to genetic testing?
Advances in prenatal screening, the development of new direct DNA tests for once rare familial diseases, and society's improved understanding and acceptance of genetic screening prior to conception, will keep genetic counselors busier than ever in the 21st century. As more and more direct DNA tests become available through the work of the Human Genome Project, genetic counselors like UMDNJ's Lorraine Suslak will become even more valuable to time-pressed physicians. Indeed, advances are made so fast in this area, that when patients come to Alan E. Donnenfeld, MD, for prenatal diagnosis, he often contacts Helix, a national organization that keeps a database of the latest tests available.


Characteristics and Outcomes Among Adults Aged ≥60 Years Hospitalized with Laboratory-Confirmed Respiratory Syncytial Virus - RSV-NET, 12 States, July 2022-June 2023.
Respiratory syncytial virus (RSV) causes substantial morbidity and mortality in older adults. In May 2023, two RSV vaccines were approved for prevention of RSV lower respiratory tract disease in adults aged ≥60 years. In June 2023, CDC recommended RSV vaccination for adults aged ≥60 years, using shared clinical decision-making. Using data from the Respiratory Syncytial Virus-Associated Hospitalization Surveillance Network, a population-based hospitalization surveillance system operating in 12 states, this analysis examined characteristics (including age, underlying medical conditions, and clinical outcomes) of 3,218 adults aged ≥60 years who were hospitalized with laboratory-confirmed RSV infection during July 2022-June 2023. Among a random sample of 1,634 older adult patients with RSV-associated hospitalization, 54.1% were aged ≥75 years, and the most common underlying medical conditions were obesity, chronic obstructive pulmonary disease, congestive heart failure, and diabetes. Severe outcomes occurred in 18.5% (95% CI = 15.9%-21.2%) of hospitalized patients aged ≥60 years. Overall, 17.0% (95% CI = 14.5%-19.7%) of patients with RSV infection were admitted to an intensive care unit, 4.8% (95% CI = 3.5%-6.3%) required mechanical ventilation, and 4.7% (95% CI = 3.6%-6.1%) died; 17.2% (95% CI = 14.9%-19.8%) of all cases occurred in long-term care facility residents. These data highlight the importance of prioritizing those at highest risk for severe RSV disease and suggest that clinicians and patients consider age (particularly age ≥75 years), long-term care facility residence, and underlying medical conditions, including chronic obstructive pulmonary disease and congestive heart failure, in shared clinical decision-making when offering RSV vaccine to adults aged ≥60 years.


Inter-laboratory evaluation of serological tests for syphilis in India: Final report on 1953-55 inquiry.
The author describes an investigation, carried out in 1953-55 under the sponsorship of the Indian Council of Medical Research, to determine the relative merits of the serological tests for syphilis in current use in the major laboratories in India. Eight laboratories were included in the survey and in each the same three tests-the Wassermann test, the Kahn standard test, and the VDRL slide precipitation test-were evaluated as to specificity, sensitivity and reproducibility. In all, 921 serum samples were examined: 376 from syphilitics, 86 from patients with non-syphilitic venereal disease, 265 from patients with non-venereal diseases, and 194 from apparently normal donors.The VDRL test proved to be the most satisfactory on the average (specificity, 97.6%; sensitivity, 95.2%; reproducibility, 87.2%) and it is therefore recommended that this test be adopted as the only routine serological test in all laboratories. From the considerable inter-laboratory variations observed in the results, it is obvious that there is room for improvement in the standard of technical performance in most of the laboratories. The author suggests that by reducing the number of different tests used to a minimum, improvement and standardization of techniques would be facilitated.


Controlled UV-C light-induced fusion of thiol-passivated gold nanoparticles.
Thiol-passivated gold nanoparticles (AuNPs) of a relatively small size, either decorated with chromophoric groups, such as a phthalimide (Au@PH) and benzophenone (Au@BP), or capped with octadecanethiol (Au@ODCN) have been synthesized and characterized by NMR and UV-vis spectroscopy as well as transmission electron microscopy (TEM). These NPs were irradiated in chloroform at different UV-wavelengths using either a nanosecond laser (266 and 355 nm, ca. 12 mJ/pulse, 10 ns pulse) or conventional lamps (300 nm < λ < 400 nm and ca. 240 nm < λ < 280 nm) and the new AuNPs were characterized by X-ray and UV-vis spectroscopy, as well as by TEM. Laser irradiation at 355 nm led to NP aggregation and precipitation, while the NPs were photostable under UV-A lamp illumination. Remarkably, laser excitation at 266 nm induced a fast (minutes time-scale) increase in the size of the NPs, producing huge spherical nanocrystals, while lamp-irradiation at UV-C wavelengths brought about nanonetworks of partially fused NPs with a larger diameter than the native NPs.


Amyotrophic lateral sclerosis-related VAPB P56S mutation differentially affects the function and survival of corticospinal and spinal motor neurons.
The substitution of Proline with Serine at residue 56 (P56S) of vesicle-associated membrane protein-associated protein B (VAPB) has been linked to an atypical autosomal dominant form of familial amyotrophic lateral sclerosis 8 (ALS8). To investigate the pathogenic mechanism of P56S VAPB in ALS, we generated transgenic (Tg) mice that heterologously express human wild-type (WT) and P56S VAPB under the control of a pan-neuronal promoter Thy1.2. While WT VAPB Tg mice did not exhibit any overt motor behavioral phenotypes, P56S VAPB Tg mice developed progressive hyperactivities and other motor abnormalities. VAPB protein was accumulated as large punctate in the soma and proximal dendrites of both corticospinal motor neurons (CSMNs) and spinal motor neurons (SMNs) in P56S VAPB Tg mice. Concomitantly, a significant increase of endoplasmic reticulum stress and unfolded protein response and the resulting up-regulation of pro-apoptotic factor CCAAT/enhancer-binding protein homologous protein expression were observed in the CSMNs and SMNs of P56S VAPB Tg mice. However, only a progressive loss of CSMNs but not SMNs was found in P56S VAPB Tg mice. In SMNs, P56S VAPB promoted a rather selective translocation of VAPB protein onto the postsynaptic site of C-boutons that altered the morphology of C-boutons and impaired the spontaneous rhythmic discharges of SMNs. Therefore, these findings provide new pathophysiological mechanisms of P56S VAPB that differentially affect the function and survival of CSMNs and SMNs in ALS8.


(18)F-fluoride PET imaging in a nude rat model of bone metastasis from breast cancer: Comparison with (18)F-FDG and bioluminescence imaging.
Clinically-relevant animal models and appropriate imaging diagnostic tools are essential to study cancer and develop novel therapeutics. We evaluated a model of bone metastasis in nude rats by micro-PET and bioluminescence imaging. A bone metastasis model was produced by intracardiac injection of osteotropic MDA-MB-231Bo-Luc human breast cancer cells into nude rats. Bioluminescence imaging and micro-PET scans using (18)F-FDG and (18)F-fluoride were acquired serially for 5 weeks. We correlated bioluminescence imaging, (18)F-FDG and (18)F-fluoride PET images, and histological slides. Multiple bone metastases were successfully evaluated by bioluminescence imaging and (18)F-FDG and (18)F-fluoride PET scans. Bioluminescence photon flux increased exponentially on weekly follow-up. (18)F-FDG PET revealed increased FDG uptake at the spine and bilaterally in the hind legs in week 2 images, and showed a progressive pattern up to 4 weeks that correlated with bioluminescence imaging. (18)F-fluoride PET showed minimal abnormal findings in week 2 images, but it showed an irregular pattern at the spine from week 3 or 4 images. On quantitative analysis with standardized uptake values, a pattern of gradual increase was observed from week 2 to week 4 in both (18)F-FDG PET and fluoride PET. Histopathological examination confirmed the formation of osteolytic metastasis and necrosis of the distal femur, which appeared as a photon defect on PET scans. Developing bone metastasis from breast cancer in a nude rat model was successfully evaluated with an animal PET imaging system and bioluminescence imaging. This nude rat model of bone metastasis, which can be evaluated by PET imaging, may be a valuable tool for evaluating early responses to novel therapeutics.


Once versus twice daily gentamicin dosing for infective endocarditis: a randomized clinical trial.
The aim of this randomized study was to investigate the effects of once versus twice daily gentamicin dosing on renal function and measures of infectious disease in a population with infective endocarditis (IE). Seventy-one IE patients needing gentamicin treatment according to guidelines were randomized to either once (n = 37) or twice daily (n = 34) doses of gentamicin. Kidney function (glomerular filtration rate, GFR) was measured with an isotope method ((51)Cr-EDTA) at the beginning of treatment and at discharge. Treatment efficacy was assessed by C-reactive protein (CRP) time to half-life, mean CRP and leukocytes. Baseline GFR was similar in the two groups. Both groups displayed a significant fall in GFR from admission to discharge. The mean decrease in GFR was as follows: with once daily gentamicin, 17.0% (95% confidence interval 7.5-26.5), and with twice daily gentamicin, 20.4% (95% confidence interval 12.0-28.8). However, there was no significant difference in the GFR decrease between the once and twice daily regimens (p = 0.573). No difference in infection parameters was demonstrated between the two dosing regimens. A twice daily gentamicin dosing regimen is neither less nephrotoxic nor more efficient than a once daily regimen in the treatment of IE patients. When indicated, gentamicin may therefore also be administered as a single-dose regimen in the treatment of IE patients.


Increasing smoke alarm operability through theory-based health education: a randomised trial.
Although working smoke alarms halve deaths in residential fires, many households do not keep alarms operational. We tested whether theory-based education increases alarm operability. Randomised multiarm trial, with a single arm randomly selected for use each day, in low-income neighbourhoods in Maryland, USA. Intervention arms: (1) Full Education combining a health belief module with a social-cognitive theory module that provided hands-on practice installing alarm batteries and using the alarm's hush button; (2) Hands-on Practice social-cognitive module supplemented by typical fire department education; (3) Current Norm receiving typical fire department education only. Four hundred and thirty-six homes recruited through churches or by knocking on doors in 2005-2008. Follow-up visits checked alarm operability in 370 homes (85%) 1-3.5 years after installation. number of homes with working alarms defined as alarms with working batteries or hard-wired and number of working alarms per home. Regressions controlled for alarm status preintervention; demographics and beliefs about fire risks and alarm effectiveness. Homes in the Full Education and Practice arms were more likely to have a functioning smoke alarm at follow-up (OR=2.77, 95% CI 1.09 to 7.03) and had an average of 0.32 more working alarms per home (95% CI 0.09 to 0.56). Working alarms per home rose 16%. Full Education and Practice had similar effectiveness (p=0.97 on both outcome measures). Without exceeding typical fire department installation time, installers can achieve greater smoke alarm operability. Hands-on practice is key. Two years after installation, for every three homes that received hands-on practice, one had an additional working alarm. http://www.clinicaltrials.gov number NCT00139126.


Cytomegalovirus infection in association with early onset pre-eclampsia.
This case describes a woman who presented with raised α-fetoprotein (AFP) on second trimester screening, and developed early onset fetal growth restriction (FGR) and severe pre-eclampsia (PET) before 24 weeks' gestation requiring magnesium sulphate and intravenous antihypertensives. Ultrasonography revealed a structurally normal fetus with estimated weight <3rd centile, abnormal uterine artery Dopplers and deteriorating fetal arterial Dopplers over the following 2 weeks. The pregnancy ended in fetal death before a viable weight was reached. Postmortem examination revealed a growth restricted fetus (birth weight <0.4th centile) and chronic villitis secondary to placental cytomegalovirus (CMV) infection. CMV has previously been associated with PET and FGR. This case highlights its potential role in the pathogenesis of placental failure and has relevance for counselling and management for future pregnancies. Furthermore, raised AFP may represent ongoing placental damage and offers potential for future therapeutic measures--for example, antivirals or immunisations to alter the natural history and prognosis of placental infection.


Improving the state of reform.
If health reform is going to work, lawmakers need to recognize that states will play a central role in reforming the health system. In doing so, reformers must address the varying health systems and stop viewing complex solutions as a poor choice. To ignore these facts is to dim the future prospects for reforming the nation's health care system.


"Lid technique": cyanoacrylate-assisted anastomosis of small-sized vessels.
This paper presents the details of an experimental study of arterial anastomosis, combining suture with the cyanoacrylate tissue adhesive. At the distal end of the vessel, two parallel incisions were made, 180 degrees apart from each other, and two sutures were placed passing from the proximal end to exit from the most distal part of the longitudinal incisions. The tissue adhesive was then applied to the proximal vessel, and the full-thickness vascular 'lid' flap was closed over it on anterior and posterior surfaces. Eighty anastomoses were carried out at the left and the right femoral arteries of 40 Wistar rats. For all of the animals, conventional end-to-end anastomosis was carried out on the left side, and the lid technique was used on the right side. There was no statistically significant difference between the patency rates of the groups (two non-patent in control and two in the study group) (P>0.05), whereas significantly reduced operation time (mean 16.2 and 10.7 min in control and study groups, respectively) (P<0.0001) and bleeding time (median 1.5 and 0.5 min in control and study groups, respectively) (P<0.0001) were documented in the study group. Histopathological evaluation of both the patent and non-patent vessels at day 21 revealed no signs of tissue toxicity or intraluminal adhesive leakage. In view of these data, it was concluded that the technique provides an effective and simple method for end-to-end anastomosis of small-calibre arteries.


Evidence for Dominant Role of Tunneling in Condensed Phases and at High Temperatures: Double Hydrogen Transfer in Porphycenes.
Investigation of the double hydrogen transfer in porphycene, its 2,7,12,17-tetra-tert-butyl derivative, and their N-deuterated isotopologues revealed the dominant role of tunneling, even at room temperature in condensed phase. Ultrafast optical spectroscopy with polarized light employed in a wide range of temperatures allowed the identification and evaluation of contributions of two tunneling modes: vibrational ground-state tunneling, occurring from the zero vibrational level, and vibrationally activated, via a large amplitude, low-frequency mode. Good correspondence was found between the rates of incoherent tunneling occurring in condensed phase and the values estimated on the basis of tunneling splittings observed in molecules isolated in supersonic jets or helium nanodroplets. The results provide solid experimental insight into widely proposed quantum facets of ubiquitous hydrogen-transfer phenomena.


Modulation of the Extent of Cooperative Structural Change During Protein Folding by Chemical Denaturant.
Protein folding and unfolding reactions invariably appear to be highly cooperative reactions, but the structural and sequence determinants of cooperativity are poorly understood. Importantly, it is not known whether cooperative structural change occurs throughout the protein, or whether some parts change cooperatively and other parts change noncooperatively. In the current study, hydrogen exchange mass spectrometry has been used to show that the mechanism of unfolding of the PI3K SH3 domain is similar in the absence and presence of 5 M urea. The data are well described by a four state N ↔ IN ↔ I2 ↔ U model, in which structural changes occur noncooperatively during the N ↔ IN and IN ↔ I2 transitions, and occur cooperatively during the I2 ↔ U transition. The nSrc-loop and RT-loop, as well as β strands 4 and 5 undergo noncooperative unfolding, while β strands 1, 2, and 3 unfold cooperatively in the absence of urea. However, in the presence of 5 M urea, the unfolding of β strand 4 switches to become cooperative, leading to an increase in the extent of cooperative structural change. The current study highlights the relationship between protein stability and cooperativity, by showing how the extent of cooperativity can be varied, using chemical denaturant to alter protein stability.


New approach for teaching health promotion in the community: integration of three nursing courses.
The complexity of the health care system and its interdisciplinary nature require that each component of the system redefine its professional framework, relative advantage, and unique contribution as an independent discipline. In choosing the most efficient and cost-effective work-force, each profession in the health care system must clarify its importance and contribution, otherwise functions will overlap and financial resources will be wasted. As rapid and wide-ranging changes occur in the health care system, the nursing profession must display a new and comprehensive vision that projects its values, beliefs, and relationships with and commitment to both patients and coworkers. The plans to fulfill this vision must be described clearly. This article presents part of a new professional paradigm developed by the nursing department of the University of Haifa, Israel. Three main topics are addressed: The building blocks of the new vision (i.e., community and health promotion, managerial skills, academic research). Integration of the building blocks into the 4-year baccalaureate degree program (i.e., how to practice health promotion with students in the community setting; managerial nursing skills at the baccalaureate level, including which to choose and to what depth and how to teach them; and academic nursing research, including the best way to teach basic research skills and implement them via a community project). Two senior student projects, demonstrating practical linking of the building blocks.


Selected case from the Arkadi M. Rywlin International Pathology Slide Seminar: sclerotic (fibroma-like) lipoma, dorsum of right hand.
Approximately 26 sclerotic lipomas have been reported since Zelger and colleagues' 1997 report of 5 cases involving the scalp and hands. In 2006, Laskin and colleagues published 21 sclerotic lipomas in a study restricted to tumors of the hands and feet. Patients' ages ranged from 7 to 72 years (mean and median 39 y); there were 12 males and 9 females; the masses, which were mostly asymptomatic and solitary, ranged from 0.6 to 2.2 cm (median 1.2 cm, mean 1.3 cm) and involved fingers (N=17), hands or wrists (N=3), and toes (N=1). Microscopically, lesions were well circumscribed, of low cellularity, and consisted of cytologically bland spindle and stellate-shaped cells with a minor component of randomly dispersed adipocytes embedded in a collagenous to myxocollagenous stroma. Eight tumors were fibroma-like with dense fibrosclerotic stroma and inconspicuous blood vessels. One tumor exhibited features of spindle cell/pleomorphic lipoma, whereas another displayed a vague onion skin-like arrangement of collagen reminiscent of a sclerotic (storiform) fibroma. The mitotic activity was negligible. Nonlipogenic cells were immunoreactive for CD99 (6/6) CD34 (6/8), S100 (4/7), and smooth muscle actin (2/6). Follow-up on 8 patients (range, 1 to 20 y, median 9.5 y) revealed no recurrence in 6 and possible persistent tumor in 2 after simple excision. The slide circulated to club members was from a 35-mm tumor on the dorsum of the right hand of a male aged 75. Club members generally agreed with a diagnosis of sclerotic lipoma but opinions differed as to whether it is a specific entity or a variant of spindle cell lipoma or dendritic fibromyxolipoma.


Extracting Attempted Hand Movements from EEGs in People with Complete Hand Paralysis Following Stroke.
This study examines the feasibility of using electroencephalograms (EEGs) to rapidly detect the intent to open one's hand in individuals with complete hand paralysis following a subcortical ischemic stroke. If detectable, this motor-planning activity could be used in real time to trigger a motorized hand exoskeleton or an electrical stimulation device that opens/closes the hand. While EEG-triggered movement-assist devices could restore function, they may also promote recovery by reinforcing the use of remaining cortical circuits. EEGs were recorded while participants were cued to either relax or attempt to extend their fingers. Linear-discriminant analysis was used to detect onset of finger-extension from the EEGs in a leave-one-trial-out cross-validation process. In each testing trial, the classifier was applied in pseudo-real-time starting from an initial hand-relaxed phase, through movement planning, and into the initial attempted-finger-extension phase (finger-extension phase estimated from typical time-to-movement-onset measured in the unaffected hand). The classifiers detected attempted-finger-extension at a significantly higher rate during both motor-planning and early attempted execution compared to rest. To reduce inappropriate triggering of a movement-assist device during rest, the classification threshold could be adjusted to require more certainty about one's intent to move before triggering a device. Additionally, a device could be set to activate only after multiple time samples in a row were classified as finger-extension events. These options resulted in some sessions with no false triggers while the person was resting, but moderate-to-high true trigger rates during attempted-movements.


Oxalomalate, a competitive inhibitor of aconitase, modulates the RNA-binding activity of iron-regulatory proteins.
We investigated the effect of oxalomalate (OMA, alpha-hydroxy-beta-oxalosuccinic acid), a competitive inhibitor of aconitase, on the RNA-binding activity of the iron-regulatory proteins (IRP1 and IRP2) that control the post-transcriptional expression of various proteins involved in iron metabolism. The RNA-binding activity of IRP was evaluated by electrophoretic mobility-shift assay of cell lysates from 3T3-L1 mouse fibroblasts, SH-SY5Y human cells and mouse livers incubated in vitro with OMA, with and without 2-mercaptoethanol (2-ME). Analogous experiments were performed in vivo by prolonged incubation (72 h) of 3T3-L1 cells with OMA, and by injecting young mice with equimolar concentrations of oxaloacetate and glyoxylate, which are the precursors of OMA synthesis. OMA remarkably decreased the binding activity of IRP1 and, when present, of IRP2, in all samples analysed. In addition, the recovery of IRP1 by 2-ME in the presence of OMA was constantly lower versus control values. These findings suggest that the severe decrease in IRP1 RNA-binding activity depends on: (i) linking of OMA to the active site of aconitase, which prevents the switch to IRP1 and explains resistance to the reducing agents, and (ii) possible interaction of OMA with some functional amino acid residues in IRP that are responsible for binding to the specific mRNA sequences involved in the regulation of iron metabolism.


Multiple roles of ADP-ribosylation factor 1 in plant cells include spatially regulated recruitment of coatomer and elements of the Golgi matrix.
Recent evidence indicates that ADP-ribosylation factor 1 (ARF1) carries out multiple roles in plant cells that may be independent from the established effector complex COPI. To investigate potential COPI-independent functions, we have followed the dynamics of ARF1 and a novel putative effector, the plant golgin GRIP-related ARF-binding domain-containing Arabidopsis (Arabidopsis thaliana) protein 1 (GDAP1) in living plant cells. We present data that ascribe a new role to ARF1 in plant cell membrane traffic by showing that the GTPase functions to recruit GDAP1 to membranes. In addition, although ARF1 appears to be central to the recruitment of both COPI components and the golgin, we have established a different subcellular distribution of these ARF1 effectors. Live cell imaging demonstrates that GDAP1 and COPI are distributed on Golgi membranes. However, GDAP1 is also found on ARF1-labeled structures that lack coatomer, suggesting that the membrane environment, rather than ARF1 alone, influences the differential recruitment of ARF1 effectors. In support of this hypothesis, fluorescence recovery after photobleaching analyses demonstrated that GDAP1 and COPI have different kinetics on membranes during the cycle of activation and inactivation of ARF1. Therefore, our data support a model where modulation of the cellular functions of ARF1 in plant cells encompasses not only the intrinsic activities of the effectors, but also differential recruitment onto membranes that is spatially regulated.


[Screening method for compounds acting at super low concentrations].
At present, there are no simple and reliable methods for selection of compounds with physiological activity in super-low concentrations (SLC). The screening system with high predictability is proposed. At the beginning, experiment is carried out on infusorians--spirostoma. Their motion activity, behavior, living ability and shape are registered at concentrations of substances in a range of 10(-3)-10(-13) mol/l. If the effect is detected on spirostoma, then experiments are performed on laboratory animals or their isolated tissues. Specific deviations on injection substance in SLC are detected, depending on compounds class. Nine representatives of different classes of biologically active compounds are investigated in the work: carbofos, deltametrin, 3-quinuclidinyl benzylate, atropine, phenosan, fenazepam, dopamine receptor antagonist SCH-23390, ciprine, and hexenal. It is accepted that if compound action in SLC is observed on spirostoma, then effects in super-low doses are also detected in a whole animal.


Aerobic exercise in people with multiple sclerosis: its feasibility and secondary benefits.
The aims of this study were to explore the feasibility of structured aerobic exercise followed by a period of unstructured physical activity and determine the impact of such exercise on cognition, mood, and quality of life in people with multiple sclerosis (MS). A convenience sample of 9 individuals with relapsing-remitting MS performed 30 minutes of aerobic exercise (upper- and lower-extremity ergometry and treadmill ambulation) twice weekly for 8 weeks, followed by 3 months of unstructured physical activity. Eight participants completed the intervention and posttest; 6 returned for the 3-month follow-up. Cardiovascular fitness, cognition, mood (measured with the Beck Depression Inventory-II; BDI-II), and quality of life (measured with the Multiple Sclerosis Quality of Life-54; MSQOL-54) were assessed. Participants completed 27.9 minutes of exercise per session, with an 85.1% attendance rate. Evaluation using the Wilcoxon signed rank test revealed no deleterious effects and improved results on the BDI-II and MSQOL-54 mental subscale. Analysis of change scores using the one-sample t test revealed that the BDI-II and MSQOL-54 were changed from zero after structured exercise, but only the BDI-II maintained improvement after unstructured physical activity. Further analysis of BDI-II subscales revealed that improvement occurred only in the Somato-Affective subscale. In this study, program feasibility was demonstrated in several ways. There were no declines in cognitive function over the 5-month period. Despite unchanged cognitive function, participants may value the improved mood enough to continue both the structured and unstructured physical activity. The role of unstructured physical activity in concert with periodic structured exercise programs merits further investigation.


Plasma IL-6 and IL-10 Concentrations Predict AKI and Long-Term Mortality in Adults after Cardiac Surgery.
Inflammation has an integral role in the pathophysiology of AKI. We investigated the associations of two biomarkers of inflammation, plasma IL-6 and IL-10, with AKI and mortality in adults undergoing cardiac surgery. Patients were enrolled at six academic centers (n = 960). AKI was defined as a ≥ 50% or ≥ 0.3-mg/dl increase in serum creatinine from baseline. Pre- and postoperative IL-6 and IL-10 concentrations were categorized into tertiles and evaluated for associations with outcomes of in-hospital AKI or postdischarge all-cause mortality at a median of 3 years after surgery. Preoperative concentrations of IL-6 and IL-10 were not significantly associated with AKI or mortality. Elevated first postoperative IL-6 concentration was significantly associated with higher risk of AKI, and the risk increased in a dose-dependent manner (second tertile adjusted odds ratio [OR], 1.61 [95% confidence interval (95% CI), 1.10 to 2.36]; third tertile adjusted OR, 2.13 [95% CI, 1.45 to 3.13]). First postoperative IL-6 concentration was not associated with risk of mortality; however, the second tertile of peak IL-6 concentration was significantly associated with lower risk of mortality (adjusted hazard ratio, 0.75 [95% CI, 0.57 to 0.99]). Elevated first postoperative IL-10 concentration was significantly associated with higher risk of AKI (adjusted OR, 1.57 [95% CI, 1.04 to 2.38]) and lower risk of mortality (adjusted HR, 0.72 [95% CI, 0.56 to 0.93]). There was a significant interaction between the concentration of neutrophil gelatinase-associated lipocalin, an established AKI biomarker, and the association of IL-10 concentration with mortality (P = 0.01). These findings suggest plasma IL-6 and IL-10 may serve as biomarkers for perioperative outcomes.


Regulation of IL-17A responses in human airway smooth muscle cells by Oncostatin M.
Regulation of human airway smooth muscle cells (HASMC) by cytokines contributes to chemotactic factor levels and thus to inflammatory cell accumulation in lung diseases. Cytokines such as the gp130 family member Oncostatin M (OSM) can act synergistically with Th2 cytokines (IL-4 and IL-13) to modulate lung cells, however whether IL-17A responses by HASMC can be altered is not known. To determine the effects of recombinant OSM, or other gp130 cytokines (LIF, IL-31, and IL-6) in regulating HASMC responses to IL-17A, assessing MCP-1/CCL2 and IL-6 expression and cell signaling pathways. Cell responses of primary HASMC cultures were measured by the assessment of protein levels in supernatants (ELISA) and mRNA levels (qRT-PCR) in cell extracts. Activation of STAT, MAPK (p38) and Akt pathways were measured by immunoblot. Pharmacological agents were used to assess the effects of inhibition of these pathways. OSM but not LIF, IL-31 or IL-6 could induce detectable responses in HASMC, elevating MCP-1/CCL2, IL-6 levels and activation of STAT-1, 3, 5, p38 and Akt cell signaling pathways. OSM induced synergistic action with IL-17A enhancing MCP-1/CCL-2 and IL-6 mRNA and protein expression, but not eotaxin-1 expression, while OSM in combination with IL-4 or IL-13 synergistically induced eotaxin-1 and MCP-1/CCL2. OSM elevated steady state mRNA levels of IL-4Rα, OSMRβ and gp130, but not IL-17RA or IL-17RC. Pharmacologic inhibition of STAT3 activation using Stattic down-regulated OSM, OSM/IL-4 or OSM/IL-13, and OSM/IL-17A synergistic responses of MCP-1/CCL-2 induction, whereas, inhibitors of Akt and p38 MAPK resulted in less reduction in MCP-1/CCL2 levels. IL-6 expression was more sensitive to inhibition of p38 (using SB203580) and was affected by Stattic in response to IL-17A/OSM stimulation. Oncostatin M can regulate HASMC responses alone or in synergy with IL-17A. OSM/IL-17A combinations enhance MCP-1/CCL2 and IL-6 but not eotaxin-1. Thus, OSM through STAT3 activation of HASMC may participate in inflammatory cell recruitment in inflammatory airway disease.


Hyperoxia in portal vein causes enhanced vasoconstriction in arterial vascular bed.
Long-term perfusion of liver grafts outside of the body may enable repair of poor-quality livers that are currently declined for transplantation, mitigating the global shortage of donor livers. In current ex vivo liver perfusion protocols, hyperoxic blood (arterial blood) is commonly delivered in the portal vein (PV). We perfused porcine livers for one week and investigated the effect of and mechanisms behind hyperoxia in the PV on hepatic arterial resistance. Applying PV hyperoxia in porcine livers (n = 5, arterial PV group), we observed an increased need for vasodilator Nitroprussiat (285 ± 162 ml/week) to maintain the reference hepatic artery flow of 0.25 l/min during ex vivo perfusion. With physiologic oxygenation (venous blood) in the PV the need for vasodilator could be reduced to 41 ± 34 ml/week (p = 0.011; n = 5, venous PV group). This phenomenon has not been reported previously, owing to the fact that such experiments are not feasible practically in vivo. We investigated the mechanism of the variation in HA resistance in response to blood oxygen saturation with a focus on the release of vasoactive substances, such as Endothelin 1 (ET-1) and nitric oxide (NO), at the protein and mRNA levels. However, no difference was found between groups for ET-1 and NO release. We propose direct oxygen sensing of endothelial cells and/or increased NO break down rate with hyperoxia as possible explanations for enhanced HA resistance.


Quantification of Hair Follicles in the Scalp in Mexican Mestizo Population.
There are no reports of the density of hair follicles in the scalp of Mexican mestizo population, necessitating the determination of normal references values for this population compared with other ethnic groups. To determine the average hair follicle count on the scalp in Mexican mestizo population. A total of 50 scalp samples (25 men and 25 women) from Mexican mestizo individuals aged between 19 and 60 years, with no clinical evidence of hair disease, obtained by biopsy punch at General Hospital "Dr. Manuel Gea González" were collected over 2 years. The total follicular density, vellus and terminal hair follicles, and the percentage in anagen and catagen-telogen phase were measured. χ2 was used as the basic statistical test. The mean number of total hair follicles in our Mexican mestizo population was 23.2 ± 4.2, which is lower compared with Thais, Iranians, and Caucasians. However, the ratio of terminal and vellus hair follicles was higher than in Thais, Caucasians, and African-Americans. The percentage of terminal hairs in anagen phase was lower than in the other populations, and higher in telogen, without exceeding 15%, established as the normal reference value. There was an association between sex and terminal hairs in telogen phase (p < 0.05). The average follicular density per mm2 was slightly higher compared with African-Americans and Asians. Women had more terminal hairs than men. The density of total follicles is lower in the Mexican mestizo population compared with Iranians, Thais, and Caucasians. However, the greater number of terminal hairs compared to vellus hairs gives the appearance of greater overall volume. The results of this study can be used as a reference for diseases of the scalp in the Mexican population.


Epithelial TRPV1 signaling accelerates gingival epithelial cell proliferation.
Transient receptor potential cation channel subfamily V member 1 (TRPV1), a member of the calcium-permeable thermosensitive transient receptor potential superfamily, is a sensor of thermal and chemical stimuli. TRPV1 is activated by noxious heat (> 43°C), acidic conditions (pH < 6.6), capsaicin, and endovanilloids. This pain receptor was discovered on nociceptive fibers in the peripheral nervous system. TRPV1 was recently found to be expressed by non-neuronal cells, such as epithelial cells. The oral gingival epithelium is exposed to multiple noxious stimuli, including heat and acids derived from endogenous and exogenous substances; however, whether gingival epithelial cells (GECs) express TRPV1 is unknown. We show that both TRPV1 mRNA and protein are expressed by GECs. Capsaicin, a TRPV1 agonist, elevated intracellular Ca(2+) levels in the gingival epithelial cell line, epi 4. Moreover, TRPV1 activation in epi 4 cells accelerated proliferation. These responses to capsaicin were inhibited by a specific TRPV1 antagonist, SB-366791. We also observed GEC proliferation in capsaicin-treated mice in vivo. No effects were observed on GEC apoptosis by epithelial TRPV1 signaling. To examine the molecular mechanisms underlying this proliferative effect, we performed complementary (c)DNA microarray analysis of capsaicin-stimulated epi 4 cells. Compared with control conditions, 227 genes were up-regulated and 232 genes were down-regulated following capsaicin stimulation. Several proliferation-related genes were validated by independent experiments. Among them, fibroblast growth factor-17 and neuregulin 2 were significantly up-regulated in capsaicin-treated epi 4 cells. Our results suggest that functional TRPV1 is expressed by GECs and contributes to the regulation of cell proliferation.


Effect of 2-hydroxybenzoate on the maintenance of naphthalene-degrading pseudomonads in seeded and unseeded soil.
The addition of specific nontoxic inducers of catabolic operons to contaminated sites is an approach that may enhance the efficiency of in situ biodegradation. We determined the genetic response of six pseudomonads to salicylate (also known as 2-hydroxybenzoate) added directly to 50 g of nonsterile soil samples. The strains, isolated from a polyaromatic hydrocarbon-contaminated soil, metabolized naphthalene as the sole source of available carbon, and their DNA sequences show significant homology to the nahAB genes of the degradative plasmid NAH7. Duplicate nonsterile soil cultures were incubated for up to 30 days. Experimental soil cultures were seeded with naphthalene-degrading strains (10(8) CFU g-1) originally isolated from the soil and amended with salicylate (16 or 160 micrograms g-1). Soil samples were analyzed periodically for the population density of heterotrophic bacteria and naphthalene degraders and for the abundance of the naphthalene-degradative genotype in the bacterial community. At 160 micrograms g-1, salicylate sustained the density of naphthalene degraders at the introduced density for 30 days in addition to producing a two- to sixfold increase in the occurrence in the bacterial community of DNA sequences homologous to the nah operon. No change in recoverable bacterial population densities was observed when soil samples were amended with 16 micrograms of salicylate g-1, but this concentration of salicylate induced a significant increase in the level of nah-related genes in the population.


Two types of triplicated alpha-globin loci in humans.
DNA from healthy Malaysian newborns was studied on gene maps after digestion with different restriction endonucleases. Of 65 newborns, two were found to be carriers of two different variants of triplicated alpha-globin loci. In variant no. 1, found in an Malay, the three alpha-globin genes are in an elongated DNA fragment on digestion with Eco RI and Bam HI. The third alpha-globin gene was found in a additional 3.7-kb fragment on digestion with Hpa I, Bgl II and Hind III. In variant no. 2, a new type of triplicated alpha-globin loci, found in a Chinese, the three alpha-globin genes reside in an elongated DNA fragment longer than that of variant no. 1 on digestion with Eco RI and Bam HI. The third alpha-globin gene was found in an additional 4.2-kb fragment on digestion with Hpa I and Hind III. Digestion of this variant DNA with Bg1 II produced an abnormal 16.7-kb fragment in addition to the normal 7.0-kb Bgl-II fragment. The locations of the restriction sites in the two types of triplicated alpha-globin loci are compatible with a mechanism of unequal crossing over following two different modes of misalignment.


FGF-7 modulates ureteric bud growth and nephron number in the developing kidney.
The importance of proportioning kidney size to body volume was established by clinical studies which demonstrated that in-born defecits of nephron number predispose the kidney to disease. As the kidney develops, the expanding ureteric bud or renal collecting system induces surrounding metanephric mesenchyme to proliferate and differentiate into nephrons. Thus, it is likely that nephron number is related to ureteric bud growth. The expression patterns of mRNAs encoding Fibroblast Growth Factor-7 (FGF-7) and its high affinity receptor suggested that FGF-7 signaling may play a role in regulating ureteric bud growth. To test this hypothesis we examined kidneys from FGF-7-null and wild-type mice. Results of these studies demonstrate that the developing ureteric bud and mature collecting system of FGF-7-null kidneys is markedly smaller than wild type. Furthermore, morphometric analyses indicate that mature FGF-7-null kidneys have 30+/-6% fewer nephrons than wild-type kidneys. In vitro experiments demonstrate that elevated levels of FGF-7 augment ureteric bud growth and increase the number of nephrons that form in rodent metanephric kidney organ cultures. Collectively, these results demonstrate that FGF-7 levels modulate the extent of ureteric bud growth during development and the number of nephrons that eventually form in the kidney.


The Ric-8B gene is highly expressed in proliferating preosteoblastic cells and downregulated during osteoblast differentiation in a SWI/SNF- and C/EBPbeta-mediated manner.
The Ric-8 gene encodes a guanine exchange factor (GEF) that modulates G protein-mediated signaling, exhibiting a relevant role during regulation of cell division. In mammals, two Ric-8 homologues have been reported (Ric-8A and Ric-8B), and recent studies indicate equivalent roles for each protein. Here, we show that the Ric-8B gene is negatively regulated during osteoblast differentiation by the transcription factor C/EBPβ. Only the larger C/EBPβ isoform (C/EBPβ-LAP*) downregulates Ric-8B gene promoter activity in osteoblastic cells. Accordingly, knockdown of C/EBPβ expression by small intefering RNA in osteoblastic cells results in a significant increase of Ric-8B gene expression. Transient overexpression of Brg1 or Brm, the catalytic subunits of the SWI/SNF chromatin-remodeling complex, inhibits Ric-8B promoter activity. Also, the presence of inactive SWI/SNF complexes in osteoblastic cells results in increased endogenous Ric-8B transcription, indicating that SWI/SNF activity negatively regulates Ric-8B expression. During osteoblast differentiation, Ric-8B gene repression is accompanied by changes in nucleosome placement at the proximal Ric-8B gene promoter and reduced accessibility to regulatory sequences.


Effects of RAGE Deletion on the Cardiac Transcriptome during Aging.
Cardiac aging is characterized by increased cardiomyocyte hypertrophy, myocardial stiffness, and fibrosis, which enhance cardiovascular risk. The receptor for advanced glycation end-products (RAGE) is involved in several age-related diseases. RAGE knockout (Rage-/-) mice show an acceleration of cardiac dimension changes and interstitial fibrosis with aging. This study identifies the age-associated cardiac gene expression signature induced by RAGE deletion. We analyzed the left ventricle transcriptome of 2.5-(Young), 12-(Middle age, MA), and 21-(Old) months-old female Rage-/- and C57BL/6N (WT) mice. By comparing Young, MA, and Old Rage-/- versus age-matched WT mice, we identified 122, 192, and 12 differently expressed genes, respectively. Functional inference analysis showed that RAGE deletion is associated with: (i) down-regulation of genes involved in antigen processing and presentation of exogenous antigen, adaptive immune response, and cellular responses to interferon beta and gamma in Young animals; (ii) up-regulation of genes related to fatty acid oxidation, cardiac structure remodeling and cellular response to hypoxia in MA mice; (iii) up-regulation of few genes belonging to complement activation and triglyceride biosynthetic process in Old animals. Our findings show that the age-dependent cardiac phenotype of Rage-/- mice is associated with alterations of genes related to adaptive immunity and cardiac stress pathways.


Relation Between Central Venous, Peripheral Venous and Arterial Lactate Levels in Patients With Sepsis in the Emergency Department.
Sepsis and multi-organ failure remain a major clinical problem with high morbidity and mortality worldwide. Lactate measurement remains part of the initial assessment and management of patients with sepsis. Although arterial blood is most commonly used for lactate measurement, there is increasing use of peripheral venous lactate for initial assessment and for monitoring of response to treatment in patients with sepsis. The aim of this study was to evaluate the relation between lactate levels measured from central line, peripheral vein and arterial line in patients treated for sepsis in the emergency department (ED). This prospective study enrolled 31 patients with diagnosis of sepsis who were evaluated and treated in the ED of a university hospital. During initial resuscitation, blood samples from the artery, peripheral vein and central vein (when available) were collected and lactate concentrations were measured. Correlation between lactate values from the three different locations was assessed using Pearson correlation. Bland-Altman plots were used to evaluate agreement between lactate measurements in different sampling locations. All patients were eventually admitted to the Internal Medicine Department ward or to the intensive care unit (ICU) for further treatment. Our data showed strong, highly significant correlation between arterial and peripheral venous lactate levels (r = 0.880, P < 0.0001), between arterial and central venous blood lactate (r = 0.898, P < 0.0001) and between central and peripheral venous blood lactate (r = 0.941, P < 0.0001). In this study we observed strong correlation between arterial, central vein and peripheral vein lactate concentrations in 31 patients assessed and treated for sepsis. We suggest that lactate measurement in peripheral venous blood could be used for screening and for monitoring response to therapy in sepsis patients. However, because this is a small study in only 31 patients and published data are limited, larger studies are needed in order to confirm the validity of our findings.