Clear cell ependymoma: a clinicopathologic and radiographic analysis of 10 patients.
Clear cell ependymoma (CCE) is an uncommon central nervous system tumor with a predilection for the supratentorial region in children. Histologically, it may mimic oligodendroglioma, central neurocytoma, hemangioblastoma, and renal cell carcinoma. The authors reviewed the clinical, radiographic, and pathologic features, therapy, and outcome in 10 children with CCE who were treated at St. Jude Children's Research Hospital (1984-2003). Fluorescence in situ hybridization (FISH) was performed using 1p/1q, 19p/19q, CEP18/DAL1, and bcr/NF2 probe pairs. The median patient age at diagnosis was 7.5 years (range, 1-19 years). Tumors occurred supratentorially in 9 of 10 patients. All tumors had rounded nuclei with surrounding, clear halos and at least focal perivascular pseudorosettes. Seven tumors had anaplastic features. No deletions involving 1p, 19q, or NF2 were detected. The tumors from 5 of 7 patients, all with anaplasia, had losses of both CEP18 and DAL-1. Radiographically, all tumors were enhanced, and 9 tumors had associated cysts with enhancing walls. Seven patients underwent gross total resection, which was near total in one patient and subtotal in two patients. Five patients received immediate postoperative local radiotherapy. Three patients were diagnosed initially with pilocytic astrocytoma (one patient) and oligodendroglioma (two patients) and were observed. The progression-free survival and overall survival rates at 5 years were 34% +/- 20% and 75% +/- 19%, respectively. The median follow-up was 37 months (range, 5-239 months). Five patients developed local recurrence within a median of 9 months after diagnosis. Two patients developed extracranial soft tissue and lymph node metastases. CCEs were found to have a predilection for extraneural metastases and early recurrence and demonstrate characteristic radiographic features, anaplastic histologic features, and chromosome 18 losses. The authors recommend resection followed by local radiotherapy as the treatment of choice in children.


Cumulative Diastolic Blood Pressure Burden in Normal Systolic Blood Pressure and Cardiovascular Disease.
The clinical significance of isolated diastolic hypertension defined by the 2017 American College of Cardiology/American Heart Association blood pressure (BP) guidelines remains inconsistent. We examined whether long-term diastolic burden predicts the first major adverse cardiovascular event in participants with sustained and untreated normal systolic BP. The Mass General Brigham Biobank is a New England health care-based cohort recruited between 2010 and 2021. A total of 15 979 participants aged 18 to 64 years and without prior cardiovascular disease, antihypertensives, or high systolic BP were studied. The cumulative diastolic burden was determined as the area under the curve for diastolic BP (DBP) ≥80 mm Hg over 5 years before enrollment. Major adverse cardiovascular event was defined as a composite of first incident ischemic heart disease, stroke, heart failure, or all-cause death. Of the 15 979 participants, mean (SD) age at enrollment was 47.6 (14.3) years, 11 950 (74.8%) were women, and the mean (SD) systolic BP and DBP were 118.0 (12.9) and 72.2 (9.3) mm Hg, respectively. Over a median (interquartile range) follow-up of 3.5 (1.8-5.4) years, 2467 (15.4%) major adverse cardiovascular events occurred. Using Cox proportional hazards regression, each SD increase in cumulative DBP was independently associated with a hazard ratio (95% CI) of 1.06 (1.02-1.10) without effect modification by sex (P=0.65), age (P=0.46), or race/ethnicity (P=0.24). In addition to traditional risk factors, cumulative DBP modestly improved the discrimination C index (95% CI) from 0.74 (0.72-0.75) to 0.75 (0.74-0.76; likelihood ratio test, P=0.037). Among individuals with normal systolic BP, cumulative DBP may augment cardiovascular disease risk stratification beyond a single DBP measure and traditional risk factors.


Development of a methodology to compute solvation free energies on the basis of the theory of energy representation for solutions represented with a polarizable force field.
We have developed a method of molecular simulations utilizing a polarizable force field in combination with the theory of energy representation (ER) for the purpose of establishing an efficient and accurate methodology to compute solvation free energies. The standard version of the ER method is, however, based on the assumption that the solute-solvent interaction is pairwise additive for its construction. A crucial step in the present method is to introduce an intermediate state in the solvation process to treat separately the many-body interaction associated with the polarizable model. The intermediate state is chosen so that the solute-solvent interaction can be formally written in the pairwise form, though the solvent molecules are interacting with each other with polarizable charges dependent on the solvent configuration. It is, then, possible to extract the free energy contribution δμ due to the many-body interaction between solute and solvent from the total solvation free energy Δμ. It is shown that the free energy δμ can be computed by an extension of the recent development implemented in quantum mechanical∕molecular mechanical simulations. To assess the numerical robustness of the approach, we computed the solvation free energies of a water and a methanol molecule in water solvent, where two paths for the solvation processes were examined by introducing different intermediate states. The solvation free energies of a water molecule associated with the two paths were obtained as -5.3 and -5.8 kcal∕mol. Those of a methanol molecule were determined as -3.5 and -3.7 kcal∕mol. These results of the ER simulations were also compared with those computed by a numerically exact approach. It was demonstrated that the present approach produces the solvation free energies in comparable accuracies to simulations of thermodynamic integration (TI) method within a tenth of computational time used for the TI simulations.


Effects of local anesthetics on pregnant uterine muscles.
Obstetric analgesia and anesthesia should provide optimal pain relief for the parturient with minimal risks. The local anesthetic agents are most commonly used for obstetric analgesia and anesthesia. We investigated the effect of local anesthetic agents: prilocaine, bupivacaine, ultracaine on myometrium in pregnant rats. In our study, we evaluated the effects of three local anesthetics at cumulative concentrations on contractions of myometrium isolated from pregnant rats. The following characteristics of the contractions were analyzed after the addition of drugs: frequency, mean duration, amplitude of each contractions and integrated area under the contraction curve. We observed that the exposure to prilocaine, bupivacaine and ultracaine decreased amplitude, duration and integrated area under the contraction curve. In conclusion, the study drugs at higher concentrations decreased contractions of myometrium, but all drugs at higher concentrations elevated the frequency.


Human Activity and Motion Pattern Recognition within Indoor Environment Using Convolutional Neural Networks Clustering and Naive Bayes Classification Algorithms.
Human Activity Recognition (HAR) systems are designed to read sensor data and analyse it to classify any detected movement and respond accordingly. However, there is a need for more responsive and near real-time systems to distinguish between false and true alarms. To accurately determine alarm triggers, the motion pattern of legitimate users need to be stored over a certain period and used to train the system to recognise features associated with their movements. This training process is followed by a testing cycle that uses actual data of different patterns of activity that are either similar or different to the training data set. This paper evaluates the use of a combined Convolutional Neural Network (CNN) and Naive Bayes for accuracy and robustness to correctly identify true alarm triggers in the form of a buzzer sound for example. It shows that pattern recognition can be achieved using either of the two approaches, even when a partial motion pattern is derived as a subset out of a full-motion path.


Determinants of non-urgent Emergency Department attendance among females in Qatar.
The use of emergency department (ED) services for non-urgent conditions is well-studied in many Western countries but much less so in the Middle East and Gulf region. While the consequences are universal-a drain on ED resources and poor patient outcomes-the causes and solutions are likely to be region and country specific. Unique social and economic circumstances also create gender-specific motivations for patient attendance. Alleviating demand on ED services requires understanding these circumstances, as past studies have shown. We undertook this study to understand why female patients with low-acuity conditions choose the emergency department in Qatar over other healthcare options. Prospective study at Hamad General Hospital's (HGH) emergency department female "see-and-treat" unit that treats low-acuity cases. One hundred female patients were purposively recruited to participate in the study. Three trained physicians conducted semi-structured interviews with patients over a three-month period after they had been treated and given informed consent. The study found that motivations for ED attendance were systematically influenced by employment status as an expatriate worker. Forty percent of the sample had been directed to the ED by their employers, and the vast majority (89%) of this group cited employer preference as the primary reason for choosing the ED. The interviews revealed that a major obstacle to workers using alternative facilities was the lack of a government-issued health card, which is available to all citizens and residents at a nominal rate. Reducing the number of low-acuity cases in the emergency department at HGH will require interventions aimed at encouraging patients with non-urgent conditions to use alternative healthcare facilities. Potential interventions include policy changes that require employers to either provide workers with a health card or compel employees to acquire one for themselves.


Conditionally replicative adenovirus expressing degradation-resistant p53 for enhanced oncolysis of human cancer cells overexpressing murine double minute 2.
Conditionally replicative adenoviruses (CRAd) are under investigation as anticancer agents. Previously, we found that the CRAd AdDelta24-p53, expressing the p53 tumor suppressor protein from its genome, more effectively killed most human cancer cells than did its parent AdDelta24. However, a minority of cancer cell lines poorly responded to the oncolysis-enhancing effect of p53. Here we show that refractory cell lines expressed high levels of the major negative p53 regulator murine double minute 2 (MDM2). To obviate MDM2-mediated inactivation of CRAd-encoded p53, we constructed the new CRAd AdDelta24-p53(14/19) encoding a p53 variant incapable of binding to MDM2. AdDelta24-p53(14/19) was approximately 10 times more effective than AdDelta24-p53 in killing cancer cell lines with high levels of human MDM2, but not cells with low MDM2. This finding supports the notion that exogenous expression of functional p53 augments the anticancer efficacy of CRAds. In addition, it confirms that high MDM2 expression is a molecular determinant of resistance against oncolysis enhancement by exogenous wild-type p53. Moreover, it shows that efficacy enhancement by restoration of functional p53 can also be accomplished in cancer cells expressing a p53 inhibitor. This further expands the utility of CRAds expressing functional p53 variants for effective virotherapy of cancer and thus their possible contribution to the advancement of individualized molecular medicine.


Investigation of a novel SMS fiber based planar multimode waveguide and its sensing performance.
A novel, MMI-based all-fiber structure, which consists of two single-mode fibers and a multimode fiber polished on both sides, is described. The light propagation characteristics of this fiber structure, as well as its superior sensing performance, are analyzed theoretically by using the beam propagation method (BPM). This fiber structure demonstrates a significant spectral response to changes of the surrounding refractive index (RI), and the measured results exhibit good agreement with the predicted data. The measured average RI sensitivity is as high as 151.29 nm/RIU over an RI range from 1.3450 to 1.4050, when the polished depth is 30 µm on both sides of the multimode fiber. This fiber structure can be an advantageous platform for various applications, especially for a lab-on-fiber type sensing application.


Intraoperative laparoscopic detection of sentinel lymph nodes with indocyanine green and superparamagnetic iron oxide in a swine gallbladder cancer model.
Mapping of sentinel lymph nodes (SLNs) can enable less invasive surgery. However, mapping is challenging for cancers of difficult-to-access visceral organs, such as the gallbladder, because the standard method using radioisotopes (RIs) requires preoperative tracer injection. Indocyanine green (ICG) and superparamagnetic iron oxide (SPIO) have also been used as alternative tracers. In this study, we modified a previously reported magnetic probe for laparoscopic use and evaluated the feasibility of detecting SLNs of the gallbladder using a laparoscopic dual tracer method by injecting ICG and SPIO into five swine and one cancer-bearing swine. The laparoscopic probe identified SPIO nanoparticles in the nodes of 4/5 swine in situ, the magnetic field counts were 2.5-15.9 μT, and fluorescence was detected in SLNs in all five swine. ICG showed a visual lymph flow map, and SPIO more accurately identified each SLN with a measurable magnetic field quite similar to the RI. We then developed an advanced gallbladder cancer model with lymph node metastasis using recombination activating gene 2-knockout swine. We identified an SLN in the laparoscopic investigation, and the magnetic field count was 3.5 μT. The SLN was histologically determined to be one of the two metastatic lymph nodes. In conclusion, detecting the SLNs of gallbladder cancer in situ using a dual tracer laparoscopic technique with ICG and SPIO was feasible in a swine model.


[Participation of adenylate cyclase in conducting hormonal signals through membranes].
Mechanisms are considered which conduct and amplify a hormonal signal with participation of adenylate cyclase. It is shown that cell sensitivity to hormone is governed by the constant of receptor affinity for hormone, by the content of receptors in the membrane as well as of the degree of receptors conjugation with the enzyme. Mechanisms regulating the amount of receptors in the membrane, the role of guanylic and other purine nucleotides in their functioning are discussed. Properties of GTR-dependent proteins realizing the functional conjugation of receptors with adenylate cyclase and models of adenylate cyclase complex molecular organization and functioning in the membrane are discussed. The complex of catalytic subunit with GTP-dependent protein is a choloenzyme of adenylate cyclase. An assumption is made that not only GTP but also GDP may influence the formation of this complex. The adenylate cyclase activity is regulated by variations in the equilibrium between apo- and choloenzyme, different agents changing this equilibrium, affecting either protein-protein of protein-nucleotide interaction. The presence of several GTP-dependent centres is supposed to be in the adenylate cyclase complex, in one of which GDP may be transformed to GTP due to the phosphotranspherase reaction.


[Effect of basic therapy on clinical symptoms, quality of life and systemic inflammation in patients with chronic obstructive pulmonary disease].
The study included 38 men with moderately severe chronic obstructive pulmonary disease (COPD) (mean age 60.6 ± 10.2 yr) and 42 ones with severe COPD (mean age 61.2 ± 7.2 yr). They were treated with tiotropium bromide, formoterol and beclomethasone dipropionate for 24 weeks (stage 1), TB alone for 12 weeks (stage 2) and TB+formoterol (long-acting bronchodilators, LABD) for another 12 weeks. Each stage was followed by evaluation of COPD symptoms using the St-George's Hospital questionnaire, daily requirements for short-acting beta-2 agonists (SABA), heart rate (HR), forced expiratory volume in the 1st second (FEV-1) before and after SABA test, hemoglobin saturation with oxygen in arterial blood during pulse oxymetry before and after 6 min walking test, blood surfactant protein D level (SP-D). The control group was comprised of 34 healthy men (mean age 62.3 ± 5.8 yr). Patients with moderately severe COPD experienced worsening of clinical symptoms (p < 0.001), required more SABA (p < 0.001), had increased HR (p = 0.01) and SP-D levels (p = 0.01) whereas FEV-1 (p = 0.05) decreased during stage 2 as compared with stage 1. Positive dynamics of all these variables except COPD symptoms and HR was observed at stage 3. Alteration in the extent of basal therapy in patients with stage III COPD did not result in dynamics of clinical and laboratory characteristics. The data obtained suggest the necessity of combined therapy with LABD or triple basal therapy of moderately severe COPD and the possibility of therapy with one or two LABD having different sites of action in the patients with clinically stable stage II COPD.


JNK2 Gene Silencing for Elastic Matrix Regenerative Repair.
Elastic fibers do not naturally regenerate in many proteolytic disorders, such as in abdominal aortic aneurysms, and prevent restoration of tissue homeostasis. We have shown drug-based attenuation of the stress-activated protein kinase, JNK-2 to stimulate elastic matrix neoassembly and to attenuate cellular proteolytic activity. We now investigate if JNK2 gene knockdown with small interfering RNA (siRNA) provides greater specificity of action and improved regenerative/antiproteolytic outcomes in a proteolytic injury culture model of rat aneurysmal smooth muscle cells (EaRASMCs). A siRNA dose of 12.5 nM delivered with a transfection reagent significantly enhanced downstream elastic fiber assembly and maturation versus untreated EaRASMC cultures. The optimal siRNA dose was also delivered as a complex with a polymeric transfection vector, polyethyleneimine (PEI) in preparation for future in vivo delivery. Linear 25 kDa PEI-siRNA (5:1 molar ratio of amine to phosphate) and linear 40 kDa PEI-siRNA (2.5:1 ratio) were effective in downregulating the JNK2 gene, and significantly increasing expression of elastic fiber assembly proteins, and decreases in elastolytic matrix metalloprotease-2 versus treatment controls to significantly increase mature elastic fiber assembly. The current work has identified siRNA dosing and siRNA-PEI complexing conditions that are safe and efficient in stimulating processes contributing to improved elastic matrix neoassembly via JNK2 gene knockdown. The results represent a mechanistic basis of a broader therapeutic approach to reverse elastic matrix pathophysiology in tissue disorders involving aberrations of elastic matrix homeostasis, such as in aortic aneurysms. Impact statement The elastic matrix and elastic fibers are key components of the structural extracellular matrix of elastic tissues and are essential to their stretch and recoil and to maintain healthy cell phenotype. Regeneration and repair of elastic matrix is naturally poor and impaired and is an unresolved challenge in tissue engineering. In this work, we investigate a novel gene silencing approach based on inhibiting the JNK2 gene, which provides significant downstream benefits to elastic fiber assembly and maturation. Combined with novel delivery strategies such as nanoparticles, we expect our approach to effect in situ elastic matrix repair in the future.


Secondary amyloidosis and gastrointestinal stromal tumors. A case report and discussion of pathogenesis.
A 69-year-old man presented with a malignant gastrointestinal stromal tumor associated with secondary amyloidosis. The tumor had classic features of a malignant gastrointestinal stromal tumor with interlacing fascicles and whorls of spindled cells, numerous and conspicuous mitotic figures, and extensive coagulative necrosis. The cells stained diffusely for CD117 (c-Kit), confirming the diagnosis of gastrointestinal stromal tumor. The spleen, 1 adrenal gland, and part of the pancreas were removed en block with the stomach. By microscopy, the spleen and adrenal gland were partially replaced with amyloid deposits confirmed by Congo red staining, electron microscopy, and immunohistochemistry. In contrast, neither the tumor nor the surrounding vasculature showed amyloid deposition. To our knowledge, this represents only the second case of systemic amyloidosis associated with a gastrointestinal stromal tumor. This case is unique in that extensive, diffuse amyloid deposits were observed in the spleen, adrenal gland, and liver.


Near-infrared heavy-metal-free SnSe/ZnSe quantum dots for efficient photoelectrochemical hydrogen generation.
Solar-driven photoelectrochemical (PEC) hydrogen production is one of the most effective strategies for solar-to-hydrogen energy conversion. Among various types of semiconductors used for PEC anodes, colloidal quantum dots (QDs) have been widely used as new and promising absorbers for PEC and other optoelectronic devices. However, currently, most efficient optoelectronic devices contain toxic Pb/Cd elements or non-earth-abundant elements (In/Ag). It is still a challenge to produce Pb/Cd-free QDs without using any toxic and non-earth-abundant elements. Here, we synthesized SnSe QDs via a diffusion-controlled hot injection approach and further stabilized the as-prepared SnSe QDs via a cation exchange reaction. The as-synthesized Zn-stabilized SnSe QDs (SnSe/ZnSe) have an orthorhombic crystal structure with indirect bandgaps ranging from 1 to 1.37 eV. Zn stabilization can significantly decrease the number of QD surface metallic Sn bonds, thereby decreasing the number of recombination centers of defects/traps. As a proof-of-concept, SnSe/ZnSe QDs are used as light absorbers for PEC hydrogen production, leading to a saturated photocurrent density of 7 mA cm-2, which is comparable to best values reported for PEC devices based on toxic-metal-free QDs. Our results indicate that Zn-stabilized SnSe QDs have great potential for use in emerging optoelectronic devices.


Recombinant activated factor VIIa use in massive transfusion and coagulopathy unresponsive to conventional therapy.
We report a retrospective analysis of patients admitted to a tertiary intensive care unit who received recombinant activated factor VIIa (rFVIIa) in an effort to control life-threatening haemorrhage and coagulopathy. Data extracted included: demographics, diagnoses and clinical course, dosage of rFVIIa, blood product requirements and coagulation tests prior to and after rFVIIa, pH, base deficit and temperature. During the study period rFVIIa was given to nine patients with refractory coagulopathy in imminent danger of death. Three patients were post cardiac surgery, three patients had multiple blunt trauma, one patient had a close range shotgun wound to the abdomen, one patient had a ruptured iliac artery aneurysm and one patient was post caesarean section with acute fatty liver of pregnancy. Improvements in prothrombin time (PT) (median 17s pre vs 10.6s post rFVIIa (P < 0.05)) were seen in all nine cases. Reduced requirements for red blood cells, fresh frozen plasma, platelets and cryoprecipitate followed rFVIIa administration in eight cases. One patient died after 48 hours of complications unrelated to the initial pathology. Seven patients were discharged from hospital; one remains in hospital. rFVIIa provided improvement in coagulopathy unresponsive to conventional therapy.


Identification of Cannabis sativa L. (hemp) Retailers by Means of Multivariate Analysis of Cannabinoids.
In this work, the concentration of nine cannabinoids, six neutral cannabinoids (THC, CBD, CBC, CBG, CBN and CBDV) and three acidic cannabinoids (THCA CBGA and CBDA), was used to identify the Italian retailers of Cannabis sativa L. (hemp), reinforcing the idea that the practice of categorizing hemp samples only using THC and CBD is inadequate. A high-performance liquid chromatography/high-resolution mass spectrometry (HPLC-MS/MS) method was developed for screening and simultaneously analyzing the nine cannabinoids in 161 hemp samples sold by four retailers located in different Italian cities. The hemp samples dataset was analyzed by univariate and multivariate analysis with the aim to identify the hemp retailers without any other information on the hemp samples like Cannabis strains, seeds, soil and cultivation characteristics, geographical origin, product storage, etc. The univariate analysis highlighted that the hemp samples could not be differentiated by using any of the nine cannabinoids analyzed. To evaluate the real efficiency of the discrimination among the four hemp retailers a partial least squares discriminant analysis (PLS-DA) was applied. The PLS-DA results showed a very good discrimination between the four hemp retailers with an explained variance of 100% and low classification errors in both calibration (5%) and cross validation (6%). A total of 92% of the hemp samples were correctly classified by the cannabinoid variables in both fitting and cross validation. This work contributed to show that an analytical method coupled with multivariate analysis can be used as a powerful tool for forensic purposes.


Vaccinations for rheumatoid arthritis.
Patients with rheumatoid arthritis (RA) suffer an increased burden of infectious disease-related morbidity and mortality and have twice the risk of acquiring a severe infection compared to the general population. This increased risk is not only a result of the autoimmune disease but is also attributed to the immunosuppressive therapies that are commonly used in this patient population. Given the increase in infection-related risks in RA, there is great interest in mitigating such risk. A number of vaccines are available to the rheumatologist, with a handful that are of importance for RA patients in the United States. The goal of this paper is to highlight the most recent literature on the key vaccines and the specific considerations for the rheumatologist and their RA patients, with a particular focus on influenza, pneumococcal, and herpes zoster vaccines. It is important for rheumatologist to understand and be aware of which vaccines are live and what potential contraindications exist for giving vaccines to RA patients.


Persisting insomnia following traumatic brain injury.
Persisting insomnia secondary to traumatic brain injury, rarely reported and documented, is described in an adult male following head injury. The neuronal mechanisms underlying this sleep disorder as well as the neuropsychological concomitants and therapeutic approaches are discussed.


In vivo 31P magnetic resonance spectroscopy study of mouse cerebral NAD content and redox state during neurodevelopment.
Nicotinamide adenine dinucleotide (NAD) is an important cofactor of energy-producing pathways. The redox ratio (NAD+/NADH) reflects the cellular oxidoreductive state. Oxidative stress and redox dysregulation have been suggested to contribute to various neurological diseases. The assessment of NAD content has been recently demonstrated in large animals and human brains by 31P magnetic resonance spectroscopy. However, its measurement in small rodents has never been attempted. The purpose of this study was to investigate, in vivo, the NAD content during mouse brain neurodevelopment. 31P-MR-spectra were acquired in the mouse brain at postnatal days P20, P40, P90 and P250 at 14.1 T using a 3D-localization sequence. High spectral quality was achieved at 14.1 T. NAD+ and NADH were quantified with mean Cramér-Rao lower bound of 10% and 14%, respectively. An increase in NAD+/NADH was observed from P20 to P250 due to a decrease in [NADH]. The intracellular pH was significantly reduced with age, while the free [Mg2+] in the brain was significantly increased. This study demonstrates for the first time the feasibility of the measurement of NAD content in vivo in mouse brains during development, which opens the prospect of longitudinally studying energy metabolism and redox dysfunction in mouse models of brain pathology.


Development and piloting of a community health worker-based intervention for the prevention of diabetes among New Zealand Maori in Te Wai o Rona: Diabetes Prevention Strategy.
The progression from impaired glucose tolerance (IGT)/impaired fasting glucose (IFG) to type 2 diabetes can be prevented or delayed through intensive lifestyle changes. How to translate this to implementation across whole communities remains unclear. We now describe the results to a pilot of a personal trainer (Maori Community Health Worker, MCHW) approach among Maori in New Zealand. A randomised cluster-controlled trial of intensive lifestyle change was commenced among 5,240 non-pregnant Maori family members without diabetes from 106 rural and 106 urban geographical clusters. Baseline assessments included lifestyle questionnaires, anthropometric measurements and venesection. A pilot study (Vanguard Study) cohort of 160 participants were weighed before and during MCHW intervention, and compared with fifty-two participants weighed immediately before intervention and with 1,143 participants from the same geographical area. Interactions between participants and the MCHW were reported using personal digital assistants with a programmed detailed structured approach to each interview. During the Vanguard Study, participants and MCHW found the messages, toolkit and delivery approach acceptable. Those with IGT/IFG diagnosed (n 27) experienced significant weight loss after screening and during the Vanguard Study (5.2 (sd 6.6) kg, paired t test P < 0.01). Significant weight loss occurred during the Vanguard Study among all participants (-1.3 (sd 3.6) kg, P < 0.001). Comparable initial weight loss was shown among those with IGT/IFG and those from existing trials. Community-wide prevention programmes are feasible among Maori and are likely to result in significant reductions in the incidence of diabetes.


Small heat shock proteins and α-crystallins: dynamic proteins with flexible functions.
The small heat shock proteins (sHSPs) and the related α-crystallins (αCs) are virtually ubiquitous proteins that are strongly induced by a variety of stresses, but that also function constitutively in multiple cell types in many organisms. Extensive research has demonstrated that a majority of sHSPs and αCs can act as ATP-independent molecular chaperones by binding denaturing proteins and thereby protecting cells from damage due to irreversible protein aggregation. As a result of their diverse evolutionary history, their connection to inherited human diseases, and their novel protein dynamics, sHSPs and αCs are of significant interest to many areas of biology and biochemistry. However, it is increasingly clear that no single model is sufficient to describe the structure, function or mechanism of action of sHSPs and αCs. In this review, we discuss recent data that provide insight into the variety of structures of these proteins, their dynamic behavior, how they recognize substrates, and their many possible cellular roles.


Multiplexed microRNA detection using lanthanide-labeled DNA probes and laser ablation inductively coupled plasma mass spectrometry.
In the past decade, microRNAs (miRNAs) have drawn increasing attention due to their role in regulation of gene expression. Especially, their potential as biomarkers in disease diagnostics has motivated miRNA research, including the development of simple, accurate, and sensitive detection methods. The narrow size range of miRNAs (20-24 nucleotides) combined with the chemical properties of conventional reporter tags has hampered the development of multiplexed miRNA assays. In this study, we have used lanthanide-labeled DNA probes for the detection of miRNAs on membranes using laser ablation inductively coupled plasma mass spectrometry (LA-ICPMS). Three miRNAs from Arabidopsis thaliana were analyzed simultaneously with high specificity, and the sensitivity of the method was comparable to radioactive detection (low femtomol range). The perspective of the developed method is highly multiplexed and quantitative miRNA analysis with high specificity and sensitivity.


Occupational Noise Exposure and Longitudinal Hearing Changes in Post-9/11 US Military Personnel During an Initial Period of Military Service.
Auditory impairments, particularly those resulting from hazardous occupational noise exposures, are pressing concerns for the US Departments of Defense (DoD) and Veterans Affairs (VA). However, to date, no studies have estimated the rate of hearing threshold change that occurs during service or how changes may vary by military occupation. Hearing threshold changes during military service have historically been reported as the proportion of Service members demonstrating a significant threshold shift. This approach does not capture the rate of the hearing threshold change or the specific audiometric frequencies impacted. Determining the rate of hearing threshold change, and factors that affect the rate of change, is important to elucidate the impact of military service on hearing and to guide prevention strategies and subsequent hearing health care. Our primary objective was to estimate the annual rate of hearing threshold change during military service as a consequence of military occupational noise exposure ranking. We linked audiometric data, collected from military personnel as part of a DoD hearing conservation program, to data describing demographic and military-service characteristics obtained from individuals enrolled in the Noise Outcomes In Service members Epidemiology Study. The analytic cohort included Veterans who enlisted in military service after September 2001 (n = 246). We examined the longitudinal association between military occupations categorized as having a low, moderate, or high noise exposure ranking and pure-tone hearing thresholds (500 to 6000 Hz) using a hierarchical linear model. The average annual rate of hearing threshold change and their 95% confidence intervals were estimated by service branch, military occupational noise exposure ranking, and audiometric test frequency. On average, hearing threshold change ranged between -0.5 and 1.1 dB/year and changes over time varied by service branch, audiometric test frequency, and military occupation noise ranking. Generally, higher test frequencies (3000 to 6000 Hz) and military occupations with moderate or high noise exposure rankings had the greatest average annual rates of hearing threshold change; however, no dose-response relationship was observed. Among Marine Corps personnel, those exposed to occupations with high noise rankings demonstrated the greatest average annual rate of change (1.1 dB/year at 6000 Hz). Army personnel exposed to occupations with moderate noise rankings demonstrated the greatest average annual rate of change (0.6 dB/year at 6000 Hz). This study (1) demonstrates the unique use of DoD hearing conservation program data, (2) is the first analysis of hearing threshold changes over time using such data, and (3) adds to the limited literature on longitudinal changes in hearing. The difference in hearing threshold changes across military branches is likely indicative of their varying noise exposures, hearing protection device use and enforcement, and surveillance practices. Results suggest Marine Corps and Army personnel are at risk for hearing threshold changes and that, among Army personnel, this is most pronounced among those exposed to moderate levels of occupational noise exposure. Estimates of the rate of hearing threshold change by frequency and factors that impact hearing are useful to inform the DoD's efforts to protect the hearing of their Service members and to the Veterans Affairs's efforts to identify and rehabilitate those most likely to experience hearing threshold change.


Validation of a simple extraction procedure for bisphenol A identification from human plasma.
The general population is exposed to bisphenol A (BPA) orally, parenterally, transdermally, and environmentally as a result of the use of BPA in food packaging, plastics, and personal care products. The majority of the population nowadays (91-99%) has detectable levels of BPA inside their body. In this study, we successfully performed an inexpensive, rapid, and simple protein precipitation procedure for extraction of BPA from human plasma, followed by analysis by LC-MS/MS. This method was specifically developed for handling large numbers of samples with minimum cost and volume of sample. The developed method was accurate, precise, and reproducible for quantification of BPA from human plasma samples in the concentration range of 10-2000 ng/mL. The method was performed on samples from 150 healthy volunteers who were enrolled in the study. The mean of observed BPA level was 2.22 ± 9.91 ng/mL. Higher BPA levels were observed for females compare to that of males (p-value = 0.002), the BPA levels were higher in participants 33 years of age and older compared to those less than 33 years of age (p-value = 0.000), then the BPA levels higher in subjects with tap water as source of drinking (p-value = 0.005). This method may be valuable for general risk assessment of BPA for a large and varied population because of its efficiency and economical aspects.


How good are we at managing acute kidney injury in hospital?
Acute kidney injury (AKI) is a common clinical problem associated with adverse outcomes. This study identifies the incidence of AKI in two UK district general hospitals' without on-site renal services and assesses AKI management and level of nephrologist input. The AKIN classification was used to identify 1020 AKI patients over 6 months. Data were collated on patient demographics, AKI management and referral to nephrology and intensive care services. Short/long-term renal outcomes were investigated. Patients were followed up for 14 months post-discharge. Incidence of hospital-based AKI was 6.4%. Mean patient age was 73 years. There was 28.1% acute in-hospital mortality with a further 21.6% 14-month mortality. Only 8.3% of patients were referred to nephrology services for in-hospital review, and only 8.1% had outpatient nephrology follow-up. Compliance with the AKI National Confidential Enquiry into Patient Outcomes and Deaths (NCEPOD) recommendations was poor with 32.8% of patients having renal imaging and 15% of patients having acid-base status assessed. NCEPOD compliance improved with nephrology input. Patients referred to nephrology were likely to be younger with pre-existing CKD and severe AKI. 10.5% of AKI episodes were unrecognized. Forty percent of those with unrecognized AKI, (compared with 15% of recognized AKI) developed de novo or progression of pre-existing CKD. AKI in DGHs is mostly managed without nephrology input. There are significant shortcomings in AKI recognition and management in this setting. This is associated with poor mortality and long-term CKD. This study supports a need to improve the teaching and training of front-line medical staff in identifying AKI. Additionally, implementation of AKI e-alert systems may encourage early recognition and provide a prompt for renal referral.


Effects of the aminoglycoside antibiotics, streptomycin and neomycin, on neuromuscular transmission. I. Presynaptic considerations.
The effects of two aminoglycoside antibiotics, streptomycin and neomycin, were studied in voltage-clamped transected twitch fibers of the costocutaneous muscles of garter snakes (species Thamnophis). The concentration-dependent effects of each antibiotic were quantitated by measuring miniature end-plate currents (mepcs) and evoked end-plate currents (epcs) in a single fiber before and in the presence of a wide range of concentrations of each antibiotic. The amplitude and the kinetics of these currents were studied and estimates of the quantal content of evoked transmitter release determined by the direct method of mean ratios, epc/mepc. A distinct separation was obtained between the concentrations of each antibiotic which demonstrated either pre- or postsynaptic actions. Both streptomycin and neomycin produced a concentration-dependent reduction in epc amplitude at concentrations which did not reduce mepc amplitude. Thus, the primary site of action for these antibiotics was considered of presynaptic origin. Streptomycin was approximately one-tenth as active as neomycin in reducing quantal release of acetylcholine. The marked depression in epc amplitude and quantal content produced by high concentrations of each antibiotic were reversed by elevating the external calcium concentration. Double logarithmic plots of the relationship between external calcium concentration and epc amplitude yielded a slope of approximately 3.8 in control physiological solution. In the presence of blocking concentrations of each antibiotic, increasing the external calcium concentration caused a parallel shift to the right of this relationship. These results suggest that the major mechanism for the neuromuscular depression produced by these aminoglycoside antibiotics is a competitive antagonism with calcium for a common presynaptic site required for evoked transmitter release.


Studying spike trains using a van Rossum metric with a synapse-like filter.
Spike trains are unreliable. For example, in the primary sensory areas, spike patterns and precise spike times will vary between responses to the same stimulus. Nonetheless, information about sensory inputs is communicated in the form of spike trains. A challenge in understanding spike trains is to assess the significance of individual spikes in encoding information. One approach is to define a spike train metric, allowing a distance to be calculated between pairs of spike trains. In a good metric, this distance will depend on the information the spike trains encode. This method has been used previously to calculate the timescale over which the precision of spike times is significant. Here, a new metric is constructed based on a simple model of synaptic conductances which includes binding site depletion. Including binding site depletion in the metric means that a given individual spike has a smaller effect on the distance if it occurs soon after other spikes. The metric proves effective at classifying neuronal responses by stimuli in the sample data set of electro-physiological recordings from the primary auditory area of the zebra finch fore-brain. This shows that this is an effective metric for these spike trains suggesting that in these spike trains the significance of a spike is modulated by its proximity to previous spikes. This modulation is a putative information-coding property of spike trains.


London Measure of Unplanned Pregnancy: guidance for its use as an outcome measure.
The London Measure of Unplanned Pregnancy (LMUP) is a psychometrically validated measure of the degree of intention of a current or recent pregnancy. The LMUP is increasingly being used worldwide, and can be used to evaluate family planning or preconception care programs. However, beyond recommending the use of the full LMUP scale, there is no published guidance on how to use the LMUP as an outcome measure. Ordinal logistic regression has been recommended informally, but studies published to date have all used binary logistic regression and dichotomized the scale at different cut points. There is thus a need for evidence-based guidance to provide a standardized methodology for multivariate analysis and to enable comparison of results. This paper makes recommendations for the regression method for analysis of the LMUP as an outcome measure. Data collected from 4,244 pregnant women in Malawi were used to compare five regression methods: linear, logistic with two cut points, and ordinal logistic with either the full or grouped LMUP score. The recommendations were then tested on the original UK LMUP data. There were small but no important differences in the findings across the regression models. Logistic regression resulted in the largest loss of information, and assumptions were violated for the linear and ordinal logistic regression. Consequently, robust standard errors were used for linear regression and a partial proportional odds ordinal logistic regression model attempted. The latter could only be fitted for grouped LMUP score. We recommend the linear regression model with robust standard errors to make full use of the LMUP score when analyzed as an outcome measure. Ordinal logistic regression could be considered, but a partial proportional odds model with grouped LMUP score may be required. Logistic regression is the least-favored option, due to the loss of information. For logistic regression, the cut point for un/planned pregnancy should be between nine and ten. These recommendations will standardize the analysis of LMUP data and enhance comparability of results across studies.


Ectopic parathyroid adenoma localized with MIBI scintigraphy and excised with guide of macroaggregated human serum albumin injection.
Primary hyperparathyroidism is caused by an excessive amount of parathyroid hormone secreted by one or more enlarged parathyroid glands. Most commonly primary hyperparathyroidism is caused by a parathyroid adenoma. Ectopic parathyroid adenomas are rare, but they can complicate the surgical treatment and have an increased morbidity and poorer success rate. Thus, preoperative imaging is particularly valuable in this group of patients with hyperparathyroidism. Preoperative imaging has opened up a new era of minimally invasive parathyroid surgery procedures. The radioguided occult lesion localization technique has become the preferred approach to preoperative localization of nonpalpable breast lesions in several breast units. In this report, we investigated the usefulness of the radio-guided occult lesion localization technique in the identification of ectopic parathyroid adenomas. We describe the case of a 66-year-old woman who was diagnosed to be hypercalcemic. Tc-99m methoxy-isobutyl-isonitrile scintigraphy identified an ectopic parathyroid adenoma. The patient's cervical region was scanned with the probe to localize an area of maximal radiotracer uptake and the hot area was identified by a gamma probe. Careful dissection was then carried out and an enlarged ectopic parathyroid gland was removed. In conclusion, the preoperative imaging of an ectopic parathyroid adenoma and the excision of this tissue with radioguided occult lesion localization technique can open up a new era of minimally invasive parathyroid surgery.


A Computational Architecture Based on RFID Sensors for Traceability in Smart Cities.
Information Technology and Communications (ICT) is presented as the main element in order to achieve more efficient and sustainable city resource management, while making sure that the needs of the citizens to improve their quality of life are satisfied. A key element will be the creation of new systems that allow the acquisition of context information, automatically and transparently, in order to provide it to decision support systems. In this paper, we present a novel distributed system for obtaining, representing and providing the flow and movement of people in densely populated geographical areas. In order to accomplish these tasks, we propose the design of a smart sensor network based on RFID communication technologies, reliability patterns and integration techniques. Contrary to other proposals, this system represents a comprehensive solution that permits the acquisition of user information in a transparent and reliable way in a non-controlled and heterogeneous environment. This knowledge will be useful in moving towards the design of smart cities in which decision support on transport strategies, business evaluation or initiatives in the tourism sector will be supported by real relevant information. As a final result, a case study will be presented which will allow the validation of the proposal.


Prefrontal Corticotropin-Releasing Factor (CRF) Neurons Act Locally to Modulate Frontostriatal Cognition and Circuit Function.
The PFC and extended frontostriatal circuitry support higher cognitive processes that guide goal-directed behavior. PFC-dependent cognitive dysfunction is a core feature of multiple psychiatric disorders. Unfortunately, a major limiting factor in the development of treatments for PFC cognitive dysfunction is our limited understanding of the neural mechanisms underlying PFC-dependent cognition. We recently demonstrated that activation of corticotropin-releasing factor (CRF) receptors in the caudal dorsomedial PFC (dmPFC) impairs higher cognitive function, as measured in a working memory task. Currently, there remains much unknown about CRF-dependent regulation of cognition, including the source of CRF for cognition-modulating receptors and the output pathways modulated by these receptors. To address these issues, the current studies used a viral vector-based approach to chemogenetically activate or inhibit PFC CRF neurons in working memory-tested male rats. Chemogenetic activation of caudal, but not rostral, dmPFC CRF neurons potently impaired working memory, whereas inhibition of these neurons improved working memory. Importantly, the cognition-impairing actions of PFC CRF neurons were dependent on local CRF receptors coupled to protein kinase A. Additional electrophysiological recordings demonstrated that chemogenetic activation of caudal dmPFC CRF neurons elicits a robust degradation of task-related coding properties of dmPFC pyramidal neurons and, to a lesser extent, medium spiny neurons in the dorsomedial striatum. Collectively, these results demonstrate that local CRF release within the caudal dmPFC impairs frontostriatal cognitive and circuit function and suggest that CRF may represent a potential target for treating frontostriatal cognitive dysfunction.SIGNIFICANCE STATEMENT The dorsomedial PFC and its striatal targets play a critical role in higher cognitive function. PFC-dependent cognitive dysfunction is associated with many psychiatric disorders. Although it has long-been known that corticotropin-releasing factor (CRF) neurons are prominent within the PFC, their role in cognition has remained unclear. Using a novel chemogenetic viral vector system, the present studies demonstrate that PFC CRF neurons impair working memory via activation of local PKA-coupled CRF receptors, an action associated with robust degradation in task-related frontostriatal neuronal coding. Conversely, suppression of constitutive PFC CRF activity improved working memory. Collectively, these studies provide novel insight into the neurobiology of cognition and suggest that CRF may represent a novel target for the treatment of cognitive dysfunction.


RAM2, an essential gene of yeast, and RAM1 encode the two polypeptide components of the farnesyltransferase that prenylates a-factor and Ras proteins.
In the yeast Saccharomyces cerevisiae, mutations in either of two unlinked genes, RAM1 or RAM2, abolish the farnesyltransferase activity responsible for prenylation of Ras proteins and the a-factor mating pheromone. Here we report that the function of RAM1 and RAM2 genes is required for the membrane localization of Ras proteins and a-factor. The RAM2 gene was sequenced and can encode a 38-kDa protein. We examined the functional interaction of RAM2 and RAM1 by expressing the genes in Escherichia coli. Extracts derived from an E. coli strain that coexpressed RAM1 and RAM2 efficiently farnesylated a-factor peptide and Ras protein substrates. In contrast, extracts derived from E. coli strains that expressed either RAM gene alone were devoid of activity; however, when the latter extracts were mixed, protein farnesyltransferase activity was reconstituted. These results indicate that the yeast farnesyl-protein transferase is comprised of Ram1 and Ram2 polypeptides. Although Ram1 is a component of the enzyme, disruption of the RAM1 gene in yeast was not lethal, indicating that the Ram1-Ram2 farnesyltransferase is not essential for viability. In contrast, disruption of RAM2 was lethal, suggesting that Ram2 has an essential function in addition to its role with Ram1 in protein farnesylation.


Trapping the Transition State in a [2,3]-Sigmatropic Rearrangement by Applying Pressure.
Transition states are of central importance in chemistry. While they are, by definition, transient species, it has been shown before that it is possible to "trap" transition states by applying stretching forces. We here demonstrate that the task of transforming the transition state of a chemical reaction into a minimum on the potential energy surface can be achieved using hydrostatic pressure. We apply the computational extended hydrostatic compression force field (X-HCFF) approach to the educt of a [2,3]-sigmatropic rearrangement in both static and dynamic calculations and find that the five-membered cyclic transition state of this reaction becomes a minimum at pressures in the range between 100 and 150 GPa. Born-Oppenheimer molecular dynamics (BOMD) simulations suggest that slow decompression leads to a 70:30 mix of the product and the educt of the sigmatropic rearrangement. Our findings are discussed in terms of geometric parameters and electronic rearrangements throughout the reaction. To provide reference data for experimental investigations, we simulated the IR, Raman, and time-resolved UV/vis absorption spectra for the educt, transition state, and product. We speculate that the trapping of transition states by using pressure is generally possible if the transition state of a chemical reaction has a more condensed geometry than both the educt and the product, which paves the way for new ways of initiating chemical reactions.


Dystocia as a cause of untimely cesarean section.
One of the most frequent indications for cesarean section is dystocia. It is impossible to predict, difficult to identify and coincident with the rapid expiry of the expected time, so it is important to point out some mistakes in expecting vaginal delivery. The aim of this study was to examine the frequency and the length of dystocia-related cesarean delivery, as well as the vitality of the newborn immediately after birth. A prospective 3-year study was conducted including a total number of 6470 deliveries regardless of whether they were completed using cesarean section after an unsuccessful attempt of spontaneous vaginal delivery or not. The Apgar score, a proved useful tool for the assessment of the vitality of newborn children in the first minute, was used. On the basis of the established indications, 653 (10.10%) of deliveries were completed using cesarean section. Dystocia was the third most common indication for cesarean section (16.38%). Deliveries in which dystocia was established as a diagnosis lasted much longer (p = 0.030) which resulted in weaker vitality of newborn children (p = 0.000) compared to the deliveries ended by spontaneous vaginal delivery. This study shows that deliveries caused by dystocia last much longer and newborn children are of weaker vitality compared to other deliveries caused not by dystocia. Decisions concerning cesarean section must be made in a timely fashion.


Loss of system x(c)- does not induce oxidative stress but decreases extracellular glutamate in hippocampus and influences spatial working memory and limbic seizure susceptibility.
System x(c)- exchanges intracellular glutamate for extracellular cystine, giving it a potential role in intracellular glutathione synthesis and nonvesicular glutamate release. We report that mice lacking the specific xCT subunit of system x(c)- (xCT(-/-)) do not have a lower hippocampal glutathione content, increased oxidative stress or brain atrophy, nor exacerbated spatial reference memory deficits with aging. Together these results indicate that loss of system x(c)- does not induce oxidative stress in vivo. Young xCT(-/-) mice did however display a spatial working memory deficit. Interestingly, we observed significantly lower extracellular hippocampal glutamate concentrations in xCT(-/-) mice compared to wild-type littermates. Moreover, intrahippocampal perfusion with system x(c)- inhibitors lowered extracellular glutamate, whereas the system x(c)- activator N-acetylcysteine elevated extracellular glutamate in the rat hippocampus. This indicates that system x(c)- may be an interesting target for pathologies associated with excessive extracellular glutamate release in the hippocampus. Correspondingly, xCT deletion in mice elevated the threshold for limbic seizures and abolished the proconvulsive effects of N-acetylcysteine. These novel findings sustain that system x(c)-) is an important source of extracellular glutamate in the hippocampus. System x(c)(-) is required for optimal spatial working memory, but its inactivation is clearly beneficial to decrease susceptibility for limbic epileptic seizures.


Device-dependent activity estimation and decay correction of radionuclide mixtures with application to Tc-94m PET studies.
Multi-instrument activity estimation and decay correction techniques were developed for radionuclide mixtures, motivated by the desire for accurate quantitation of Tc-94m positron emission tomography (PET) studies. Tc-94m and byproduct Tc isotopes were produced by proton irradiation of enriched Mo-94 and natural Mo targets. Mixture activities at the end of bombardment were determined with a calibrated high purity germanium detector. The activity fractions of the greatest mixture impurities relative to 100% for Tc-94m averaged 10.0% (Tc-94g) and 3.3% (Tc-93) for enriched targets and 10.1% (Tc-94g), 11.0% (Tc-95), 255.8% (Tc-96m), and 7.2% (Tc-99m) for natural targets. These radioisotopes have different half-lives (e.g., 52.5 min for Tc-94m, 293 min for Tc-94g), positron branching ratios (e.g., 0.72 for Tc-94m, 0.11 for Tc-94g) and gamma ray emissions for themselves and their short-lived, excited Mo daughters. This complicates estimation of injected activity with a dose calibrator, in vivo activity with PET and blood sample activity with a gamma counter. Decay correction using only the Tc-94m half-life overestimates activity and is inadequate. For this reason analytic formulas for activity estimation and decay correction of radionuclide mixtures were developed. Isotope-dependent sensitivity factors for a PET scanner, dose calibrator, and gamma counter were determined using theoretical sensitivity models and fits of experimental decay curves to sums of exponentials with fixed decay rates. For up to 8 h after the end of bombardment with activity from enriched and natural Mo targets, decay-corrected activities were within 3% of the mean for three PET studies of a uniform cylinder, within 3% of the mean for six dose calibrator decay studies, and within 6% of the mean for four gamma counter decay studies. Activity estimation and decay correction for Tc-94m mixtures enable routine use of Tc-94m in quantitative PET, as illustrated by application to a canine Tc-94m sestamibi study.


Going beyond Radial Hydration Models: The Hidden Structures of Chloride and Iodide Aqua Ions Revealed by the Use of Lone Pairs.
A novel model of hydration for the chloride and iodide ions in water is proposed, which overcomes the limitations of conventional radial models. A new approach, based on a representation of the halide lone pairs, highlighted a subset of first shell water molecules featuring preferential strong interactions with the ion lone pairs, giving rise to tetrahedral hydration structures in both Cl- and I- aqueous solutions. By adopting a novel descriptor correlated to the halide-water interaction energy, we were able to split the conventional first solvation shell into a tight first hydration shell, composed of water molecules strongly interacting with the ions via hydrogen bonds, and a loose first shell containing molecules that are only slightly perturbed by the halide electrostatic charge. The picture emerging from our findings indicates that lone pairs play an important role in the description of systems where hydrogen bonds are the main interactions taking place in the solvation process.


[Contribution of amino acid deficiency to primary hypothyroidism associated with protein-calorie malnutrition].
A 68-year-old male patient without any previous thyroidal disease developed three times of transient primary hypothyroidism associated with protein-calorie malnutrition (PCM). Because of his diabetes mellitus, alcoholic hepatitis, chronic pancreatitis and blind loop syndrome, his nutritional balance was easily disturbed leading to PCM. Although he recurrently developed primary hypothyroidism associated with PCM, this condition was completely restored by protein-calorie repletion. The possibility of dietary iodine deficiency was negated by the observation that his daily urinary iodine secretion was more than 4 mg/day. Plasma amino acid analysis revealed severe depletion of phenylalanine, tyrosine and other essential amino acids and raised the possibility that this hypothyroidism was caused by amino acid deficiency. In order to clarify the mechanisms of this primary hypothyroidism, we have investigated the change of thyroid functions during protein-calorie repletion by total parenteral nutrition (TPN). We then removed iodine from the nutrients for TPN to ascertain that iodine deficiency was not the cause of the primary hypothyroidism in the present case. In spite of the removal of iodine, serum T4 and T3 suddenly increased from 1.1 micrograms/dl and less than 25 ng/dl to 3.5 micrograms/dl and 59 ng/dl, respectively, in a few days after the beginning of TPN. They continued to increase thereafter and reached 6.3 micrograms/dl and 115 ng/dl in 6 weeks. Serum free T4 also showed a sudden increase from 0.56 ng/dl to 1.7 ng/dl after TPN and remained above 1.3 ng/dl thereafter. Serum reverse T3 showed a rapid increase after TPN, but, 4 weeks later, returned to the previous level before TPN. Serum TSH decreased from 120 microU/ml to 17 microU/ml in a few days after TPN and reached a level within normal range in 4 weeks. Serum TBG gradually increased from 10.7 micrograms/ml to 29.2 micrograms/ml in 6 weeks. These results show that the T4 synthesis was extremely impaired by PCM in spite of the strong stimulation by TSH and that this suppression of T4 synthesis by PCM led the patient recurrently to the primary hypothyroidism. We have next investigated the possibility whether the deficiency of phenylalanine and tyrosine could cause a suppression of T4 synthesis because tyrosine is an important substrate of T4. For this purpose we removed phenylalanine and tyrosine from TPN and added iodine to prevent iodine deficiency due to prolonged iodine-depleted nutrition. Reduction of phenylalanine and tyrosine resulted in a marked decrease in serum T4, T3 and TBG in 7 weeks, but gave no change to free T4. Serum TSH remained within normal range.(ABSTRACT TRUNCATED AT 400 WORDS)


Study of the Relationship between Sensory Processing Sensitivity and Burnout Syndrome among Speech and Language Therapists.
Burnout syndrome can arise due to either situational factors such as working conditions, or dispositional factors such as certain temperaments, like a high sensory processing sensitivity. We aim to address the relative absence of studies on speech-language therapists and seek to determine the role of high sensitivity for these healthcare workers in relation to burnout syndrome. The sample consisted of 602 female speech-language pathologists who anonymously completed a questionnaire measuring burnout (ProQOL 5th edition) and sensory processing sensitivity (HSPS-FR). The results revealed that 77.41% of the participants reported moderate or high burnout scores. Furthermore, the analyses revealed that highly sensitive participants are more vulnerable to burnout than others. This study highlights the negative impact of high sensory processing sensitivity on burnout. However, according to the kind of sensitivity, we discuss the way in which highly sensitive caregivers can master this sensitivity in order to use it as a strength in their professions and to spare themselves from suffering deleterious effects, such as compassion fatigue and/or burnout.


Sinoorbital gunshot injuries. Endoscopic diagnostics and management.
Gunshot injuries to the paranasal sinuses and orbita are uncommon. Their severity depends on missile track in tissues. Such injuries can involve the orbit, paranasal sinuses, or brain. This article reports the main clinical criteria and the aspects of surgical management. Functional endoscopic sinus surgery is the most appropriate technique for removing projectiles left. This article also presents one case of airgun injury to the sphenoid sinus with retained missile that was safely removed using endoscopic procedures.


Hypoxic apnea and gasping.
We have tested the hypothesis that severe lypoxia causes apnea, regardless of the arterial CO2 and pH, and that extreme hypoxia causes gasping. Acute experiments with airway occlusion and with low inspired oxygen (FIo2) were performed on anesthetized adult dogs and monkeys. Arterial oxygen saturation was recorded continuously with fiberoptic oximetry, and Pco2 by an electrode catheter. In addition, blood samples were obtained for Po2, Pco2, and pH. Apnea was induced regularly when the Pao2 fell below 10 torr, whether the Paco2 was high with asphyxia (63 torr) or low (26 torr) with low FIo2. Similarly, the Pao2 at apnea was the same whether the pH was 7.17 with asphyxic hypoxia or 7.46 with hypoxic hypoxia. Gasping occurred at even lower Pao2 (below 5 torr) after 1 or 2 min of apnea. Gasping promptly restored the Pao2 to levels of moderate hypoxia (over 30 torr) which permitted resumption of regular respiration, with gradual elimination of the gasping. Fetal monkeys at term were studied in a similar manner from the moment of cord clamping. Their blood gases with apnea were quite similar to adult values in the narrow range of Pao2 and the wide range of Paco2 and pH. In the fetus, gasping was less immediately effective in improving arterial oxygen, but more persistent than in the adult. Regular respirations would not develop in the absence of oxygen in either the fetus or adult animal.


Relationship between noise annoyance from road traffic noise and cardiovascular diseases: a meta-analysis.
Road traffic noise is an important source of noise annoyance in the community. We performed a meta-analysis to assess whether there is an association between noise annoyance from road traffic noise and cardiovascular diseases (arterial hypertension and ischemic heart disease) in adult population. The meta-analysis included studies that: a. had noise annoyance as exposure, quantified either as "annoyed versus non-annoyed" or with various scales collected by standardized questionnaires; b. arterial hypertension or ischemic heart disease as outcome; c. had included only adult population (age >18 years); d. the studies had to have as effect size odds ratios or relative risk. From the individual studies those odds ratios were selected for meta-analysis which compared most distant categories. Eight studies that fulfilled criteria published between 1992 and 2006 were included in the meta-analysis: 6 studies had a cross-sectional design, 1 study had a case-control-design and 1 study had a cohort design. Increased annoyance was significantly associated with arterial hypertension (pooled risk estimate = 1.16, 95% confidence interval 1.02-1.29) while the association with ischemic heart disease did not reach statistical significance (pooled risk estimate = 1.07, 95% confidence interval 0.99-1.14). No publication bias was evidenced. The results of this meta-analysis demonstrated the existence of a positive and significant association between noise annoyance from road traffic and the risk of arterial hypertension and a positive yet insignificant association between noise annoyance and the risk of ischemic heart disease.


Gas chromatography/isotope-ratio mass spectrometry method for high-precision position-dependent 15N and 18O measurements of atmospheric nitrous oxide.
We describe an automated gas chromatography/isotope-ratio mass spectrometry (GC/IRMS) method for the determination of the (18)O and position-resolved (15)N content of nitrous oxide at natural isotope abundance. The position information is obtained from successive measurement of the isotopic composition of the N(2)O(+) ion at m/z 44, 45, 46 and the NO(+) fragment ion at m/z 30, 31. The fragment ion analysis is complicated by a non-linearity in the mass spectrometer that has to be taken into account. Evaluation of the absolute peak areas allows for a simultaneous determination of the N(2)O mixing ratio for atmospheric samples. Samples with mixing ratios ranging from a few nmol/mol up to the percent level can be analyzed using different sample inlet systems. The high concentration inlet system provides an easy and quick method to carry out various diagnostic tests, in particular to perform realistic linearity tests. A gas chromatographic set-up with a split column and a backflush possibility improves analytical precision and excludes interferences by substances with long retention times from preceding runs. We also describe a new open split interface that uses only a single transfer capillary to the mass spectrometer for sample and reference gas.


Normal development of the tibiofemoral angle in children: a clinical study of 590 normal subjects from 3 to 17 years of age.
In evaluation of genu varum-genu valgum, tibiofemoral (TF) angle and intercondylar (IC) or intermalleolar (IM) distance are commonly measured. In this study, we determined mean values and normal limits for TF angle and IC/IM distance in 590 normal Turkish children (287 girls and 303 boys) aged from 3 to 17 years using clinical methods. We noted a significantly higher degree of valgus angle than that in previous reports. The maximal mean valgus angle was 9.6 degrees at 7 years for boys and 9.8 degrees at 6 years for girls. These differences were considered racial differences between Turkish children and those of other races. Turkish children, aged between 3 and 17 years, exhibited < or =11 degrees physiologic valgus. A measurable varus angle or a valgus higher than 11 degrees during this period should be considered abnormal.


Immunochemistry of lysosomal storage disorders.
Lysosomal storage disorders are a group of genetic diseases, each with a broad spectrum of clinical presentation that ranges from attenuated to severe. The immunochemical analysis of patient samples is aimed at several key aspects of patient management, including early detection of the disorder, prediction of clinical severity, determining the most appropriate therapeutic regimen, and monitoring of patients on therapy. In this study, we review the current and emerging technology available to achieve these assessments. Immune assays have direct practical application for the early detection, diagnosis and prognosis of lysosomal storage disorder patients. Multiplexing of these assays may provide a platform to allow newborn screening for multiple lysosomal storage disorders. We have reviewed the immunochemical techniques available for the analysis of lysosomal storage disorder patient samples and advise that these may be used in conjunction with other technologies for effective patient management.


In vivo tumor inhibitory effects of nutritional rice bran supplement MGN-3/Biobran on Ehrlich carcinoma-bearing mice.
This study was undertaken to investigate the in vivo anti-tumor activity of MGN-3/Biobran, a modified arabinoxylan rice bran. Swiss albino mice were inoculated intramuscularly in the right thigh with Ehrlich ascites carcinoma (EAC) cells. On Day 8, mice bearing a solid Ehrlich carcinoma (SEC) tumor were treated with MGN-3 via intraperitoneal injection. Tumor growth, cytokine production, and apoptotic effect of MGN-3 were examined. MGN-3 caused a highly significant delay in both tumor volume (63.27%) and tumor weight (45.2%) as compared to controls (P < 0.01). The mechanisms by which MGN-3 exerts its antitumor effect seem to involve its ability to induce apoptosis and immune modulation. MGN-3 induced a 1.8-fold increase in the percentage of apoptotic SEC cells as determined by flow cytometry and the histopathological examination. In addition, MGN-3 influenced plasma cytokine production by increasing the levels of tumor necrosis factor-alpha and interferon-gamma, while downregulating levels of the immune suppressing cytokine interleukin-10. Data also showed that non-tumor-bearing mice intramuscularly injected with MGN-3 resulted in a twofold increase in natural killer activity. No adverse side effects due to MGN-3 treatment were observed; all animals displayed normal feeding/drinking and life activity patterns. These data may have clinical implications for the treatment of solid cancers.


Persistent body fat mass and inflammatory marker increases after long-term cure of Cushing's syndrome.
Although increased central fat mass is characteristic of active Cushing's syndrome (CS), little is known about body composition and secretion of adipokines after long-term recovery of CS. The aim of this study was to evaluate central fat mass and its correlation with adipokines and cardiovascular risk factors in patients after long-term remission of CS. Thirty-seven women with CS in remission (27 of pituitary and 10 of adrenal origin; mean age, 50 +/- 14 yr; mean time of hormonal cure, 11 +/- 6 yr) were enrolled and compared to 14 women with active CS and 85 gender-, age-, and body mass index-matched healthy controls. Total and trunk fat mass were measured by dual-energy x-ray absorptiometry scanning. Laboratory parameters and adipokine levels [including adiponectin, visfatin, soluble TNFalpha-receptor 1 (sTNF-R1), sTNF-R2, and IL-6] were measured. Cured CS patients had more total and trunk fat mass than controls. Cured and active CS had higher levels of sTNF-R1 and IL-6 and lower adiponectin levels than controls. Higher insulin levels and blood pressure in both groups of CS patients and higher apolipoprotein B in cured CS were observed compared to controls. sTNF-R1 correlated positively with percentage of trunk fat mass and remained significant after adjusting for anthropometric parameters. Despite long-term cure, patients who have suffered CS exhibit persistent accumulation of central fat, as in active hypercortisolemia, with the consequent unfavorable adipokine profile, leading to a state of low-grade inflammation. This situation determines a persistent and increased cardiovascular risk in these patients.


Money giveth, money taketh away: the dual effect of wealth on happiness.
This study provides the first evidence that money impairs people's ability to savor everyday positive emotions and experiences. In a sample of working adults, wealthier individuals reported lower savoring ability (the ability to enhance and prolong positive emotional experience). Moreover, the negative impact of wealth on individuals' ability to savor undermined the positive effects of money on their happiness. We experimentally exposed participants to a reminder of wealth and produced the same deleterious effect on their ability to savor as that produced by actual individual differences in wealth, a result supporting the theory that money has a causal effect on savoring. Moving beyond self-reports, we found that participants exposed to a reminder of wealth spent less time savoring a piece of chocolate and exhibited reduced enjoyment of it compared with participants not exposed to wealth. This article presents evidence supporting the widely held but previously untested belief that having access to the best things in life may actually undercut people's ability to reap enjoyment from life's small pleasures.


Prospective study of the prevalence, genotyping, and clinical relevance of Dientamoeba fragilis infections in an Australian population.
A prospective study was conducted over a 30-month period, in which fecal specimens from 6,750 patients were submitted to the Department of Microbiology at St. Vincent's Hospital, Sydney, Australia. Trophozoites of Dientamoeba fragilis were detected in 60 (0.9%) patients by permanent staining, and confirmation was performed by PCR. Gastrointestinal symptoms were present in all patients, with diarrhea and abdominal pain the most common symptoms. Thirty-two percent of patients presented with chronic symptoms. The average age of infected patients was 39.8 years. No correlation was found between D. fragilis and Enterobius vermicularis, a proposed vector of transmission for D. fragilis. The genetic diversity of 50 D. fragilis isolates was examined by PCR, and the PCR products were analyzed for the presence of restriction fragment length polymorphisms. These results showed no variation in the small-subunit rRNA gene and demonstrated a single genotype for all Australian isolates. This study shows the potential pathogenic properties of D. fragilis and the need for all laboratories to routinely test for this organism.


The altering of reported experiences.
The unreliability of human memory is well documented in the literature, yet psychiatrists and other mental health care professionals rely on patient self-report in history-taking. This study provides new evidence from a longitudinal study of autobiographical memory and discusses implications for the development and implementation of appropriate treatment plans and goals. Seventy-three mentally healthy 14-year-old males were studied in 1962. Sixty-seven of these subjects were reinterviewed face-to-face at age 48. Questions concerning areas of family relationships, home environment, dating, sexuality, religion, parental discipline, and general activities were asked in both interviews. Significant differences were found between adult memories of adolescence and what was actually reported during adolescence. Accurate memory was generally no better than expected by chance. If the accurate memory of one's past is not better than chance in the mentally healthy individual, even more care probably should be taken in obtaining accurate historical information in the medically, psychologically, or otherwise health-compromised individual. It would be more constructive to treat recollections as existential reconstructions.


Wound healing after anorectal surgery in human immunodeficiency virus-infected patients.
Medical records of 52 human immunodeficiency virus (HIV)-infected patients who underwent a total of 80 anorectal operations from January 1985 to January 1990 were retrospectively reviewed to determined whether anorectal surgical wounds healed in HIV-infected patients and the mean survival time of these patients after surgery. Twenty-four operations were performed in asymptomatic HIV-infected patients, 19 in HIV-infected patients with persistent lymphadenopathy, and 37 in patients with acquired immunodeficiency syndrome. Wounds healed in 49 patients (94%). The mortality rate 30 days after surgery was 2%. There were no major complications. The mean survival time of HIV-infected patients after surgery was 15 months. We conclude that anorectal surgical wounds heal in most HIV-infected patients and that the survival time after surgery of HIV-infected patients with anorectal disease justifies appropriate surgical treatment.


Overexpression of CD14, TLR4, and MD-2 in HEK 293T cells does not prevent induction of in vitro endotoxin tolerance.
TLR4 and MD-2 are necessary for conferring cellular responsiveness to LPS. Prior exposure to LPS induces a transient state of cell refractoriness to subsequent LPS re-stimulation, known as 'endotoxin tolerance'. While induction of LPS tolerance has been reported to correlate with down-regulation of cell surface expression of TLR4/MD-2, other mechanisms of LPS tolerance have been revealed that target intracellular intermediates downstream of the TLR4/MD-2 complex. In this study, we sought to examine whether endotoxin tolerance could be induced under conditions where expression of TLR4 and MD-2 proteins is not affected by LPS. Human HEK 293T cells are completely unresponsive to LPS, but acquire high LPS sensitivity following transient transfection with CD14, TLR4, and MD-2 (293T/CD14/TLR4/MD-2 cells), as judged by NF-kappaB activation, ERK 1/2 phosphorylation, and TNF-alpha gene expression. Prior exposure of 293T/CD14/TLR4/MD-2 cells to LPS resulted in a significant decrease of LPS-mediated responses, yet failed to affect expression levels of TLR4 and MD-2. Thus, altered expression and/or function of intracellular mediators downstream of the TLR4/MD-2 complex play an important role in mediating LPS tolerance.


[Prophylactic and therapeutic effect of jiawei zhigancao tang injection on experimental arrhythmia in rats].
The antiarrhythmic effect of Jiawei Zhigancao Tang injection (JZTI) was studied in experimental arrhythmia induced by aconitine or by CaCl2 in anesthetized rats. The prophylactic dose of JZTI (5g/kg, i.v.) reduced the incidence rate of premature ventricular complexes, ventricular tachycardia (P < 0.01), delayed the onset time of arrhythmia induced by CaCl2 (P < 0.01), and the recovery time of sinus rhythm occurred earlier than that of control group (P < 0.01). The therapeutic dose of JZTI (10g/kg, i.v.) raised the rate of aconitine-induced arrhythmia to sinus rhythm conversion (P < 0.05). The results showed that JZTI could significantly antagonize arrhythmia induced by aconitine or by Cacl2 in rats.


Clinics in diagnostic imaging (40). Iliotibial band syndrome.
A 51-year-old male cyclist presented with a mass over the lateral portion of his knee. MR scans showed a cystic collection deep to the iliotibial band (ITB). Diagnosis of the ITB syndrome and its differentiation from other cause of painful lateral knee masses, such as meniscal cyst, lateral collateral ligament injury and Segond fracture, are discussed.


[Therapeutic results in malignant lymphomas treated by the COPP and POPP drug administration schedules].
The paper deals with a comparison of the results of treatment of 19 patients with malignant lymphomas, mostly diffuse ones, stage 3, by POPP schedule (paphencyl, vincristine (oncovine), procarbosin (natulan) and prednisolone) and 37 similar patients who received a modified standard COPP treatment. Following six courses of POPP treatment, the frequency of complete remission was significantly higher (83 and 51% respectively). Therefore, this schedule of therapy may be recommended for a large-scale application. The assessment of the survival rates of patients who received either type of treatment required further study.


Contrasting association of a non-synonymous leptin receptor gene polymorphism with Wegener's granulomatosis and Churg-Strauss syndrome.
There is evidence that the leptin/ghrelin system is involved in T-cell regulation and plays a role in (auto)immune disorders such as SLE, RA and ANCA-associated vasculitides (AAVs). Here, we evaluate the genetic background of this system in WG. We screened variations in the genes encoding leptin, ghrelin and their receptors, the leptin receptor (LEPR) and the growth hormone secretagogue receptor (GHSR). Three single nucleotide polymorphisms (SNPs) in each gene region were analysed in 460 German WG cases and 878 ethnically matched healthy controls. A three-SNP haplotype of GHSR was significantly associated with WG [P = 0.0067; corrected P-value (P(c)) = 0.026; odds ratio (OR) = 1.30; 95% CI 1.08, 1.57], as was one non-synonymous SNP in LEPR (Lys656Asn, P = 0.0034; P(c) = 0.013; OR = 0.72; 95% CI 0.58, 0.90). These four SNPs were re-analysed in independent cohorts of 226 German WG cases and 519 controls. While the GHSR association was not confirmed, allele frequencies of the LEPR SNP were virtually identical to those from the initial cohorts. Analysis of this SNP in the combined WG and control panels revealed a significant association of the LEPR 656Lys allele with WG (P = 0.00032; P(c) = 0.0013; OR = 0.72; 95% CI 0.60, 0.86). Remarkably, the Lys656Asn SNP showed contrasting allele distribution in two cohorts of 108 and 88 German cases diagnosed with Churg-Strauss syndrome (CSS, combined P = 0.0067; OR = 1.41; 95% CI 1.10, 1.81), whereas identical allele frequencies were revealed when comparing British WG and microscopic polyangiitis cases. While GHSR has to be further evaluated, these data provide profound evidence for an association of the LEPR Lys656Asn SNP with AAV, resulting in opposing effects in WG and CSS.


Human Intestinal Enteroids as a Model System of Shigella Pathogenesis.
The enteric bacterium and intracellular human pathogen Shigella causes hundreds of millions of cases of the diarrheal disease shigellosis per year worldwide. Shigella is acquired by ingestion of contaminated food or water; upon reaching the colon, the bacteria invade colonic epithelial cells, replicate intracellularly, spread to adjacent cells, and provoke an intense inflammatory response. There is no animal model that faithfully recapitulates human disease; thus, cultured cells have been used to model Shigella pathogenesis. However, the use of transformed cells in culture does not provide the same environment to the bacteria as the normal human intestinal epithelium. Recent advances in tissue culture now enable the cultivation of human intestinal enteroids (HIEs), which are derived from human intestinal stem cells, grown ex vivo, and then differentiated into "mini-intestines." Here, we demonstrate that HIEs can be used to model Shigella pathogenesis. We show that Shigella flexneri invades polarized HIE monolayers preferentially via the basolateral surface. After S. flexneri invades HIE monolayers, S. flexneri replicates within HIE cells and forms actin tails. S. flexneri also increases the expression of HIE proinflammatory signals and the amino acid transporter SLC7A5. Finally, we demonstrate that disruption of HIE tight junctions enables S. flexneri invasion via the apical surface.


Modulation of the hydro-osmotic effect of vasopressin on the rabbit cortical collecting tubule by adrenergic agents.
The effects of catecholamines on antidiuretic hormone ([Arg(8)]-vasopressin [AVP])-induced water absorption were evaluated in cortical collecting tubules isolated from the rabbit kidney and perfused in vitro. In the presence of AVP (100 muU/ml), net fluid volume absorption (J(v), nanoliters per minute per millimeter) was 1.14+/-0.12 and osmotic water permeability coefficient (P(f), X 10(-4) centimeters per second) was 217.3+/-39.9. The addition of the alpha-adrenergic agonist, phenylephrine (PE), in a concentration of 10(-6) M resulted in a significant decrease in J(v) and P(f) to 0.83+/-0.13 (P < 0.001) and 148.8+/-41.8 (P < 0.02), respectively. Increasing the concentration of PE to 10(-5) M resulted in a further decrease in J(v) and P(f) to 0.53+/-0.05 (P < 0.05 vs. PE 10(-6) M) and 88.5+/-9.0 (P 0.05 vs. PE 10(-6) M), respectively. In a separate group of tubules, in the presence of AVP (100 muU/ml) and PE (10(-5) M), J(v) and P(f) were 0.35+/-0.07 and 66.0+/-17.3, respectively. The addition of the alpha-adrenergic antagonist, phentolamine (PH), in a concentration of 10(-6) M resulted in a significant increase in J(v) to 1.07+/-0.19 (P < 0.001) and P(f) to 193.3+/-35.9 (P < 0.005). PH (10(-5) M) alone did not significantly affect J(v) and P(f) in the presence of AVP (100 muU/ml) nor in the presence of 8-bromo adenosine 3',5' cyclic monophosphate (8-BrcAMP). J(v) and P(f) were 1.20+/-0.21 and 174.0+/-25.8, respectively, in the presence of 8-BrcAMP (10(-4) M). We next examined the effect of the beta-adrenergic agonist, isoproterenol (ISO), on J(v) and P(f) in the presence of AVP. J(v) and P(f) were 1.04+/-0.10 and 202.6+/-17.2, respectively, in the presence of AVP (100 muU/ml) and 1.06+/-0.18 and 193.4+/-27.7, respectively, in the presence of AVP (10muU/ml). However, in the presence of AVP in a concentration of 2.5 muU/ml, J(v) was 0.60+/-0.07 and P(f) was 100.7+/-24.7. ISO (10(-6) and 10(-5) M) did not have any significant effect in the presence of the above maximal and submaximal concentrations of AVP. In the absence of AVP, control J(v) was 0.01+/-0.12 and P(f) was 4.6+/-11.0. The addition of ISO at 25 or 37 degrees C did not result in any significant change in J(v) or P(f). These studies indicate that alpha-adrenergic agonists directly inhibit AVP-mediated water absorption at the level of the tubule, an effect that can be blocked by a specific alpha-adrenergic antagonist. This effect appears to be exerted at the level of activation of adenylate cyclase since it is absent in the presence of cAMP. The beta-adrenergic agonists do not directly inhibit or enhance AVP-mediated water absorption at the level of the renal tubule.


Molecular assembly and biological activity of a recombinant fragment of fibronectin (FNIII(7-10)) on poly(ethyl acrylate).
Fibronectin (FN) fibrillogenesis is a cell-mediated process involving integrin activation that results in conformational changes of FN molecules and the organization of actin cytoskeleton. A similar process can be induced by some particular chemistries in the absence of cells, e.g., poly(ethyl acrylate) (PEA), which enhance FN-FN interactions leading to the formation of a biologically active network on the material surface. We have investigated the organization of a recombinant fragment of fibronectin (FNIII(7-10)) upon adsorption on this particular chemistry, PEA. Atomic force microscopy (AFM) was used to identify individual molecules of the fragment after adsorption, as well as the evolution of the distribution of adsorbed molecules on the surface of the material as the concentration of the adsorbing solution increased. Globular molecules that turn into small aggregates were found as a function of solution concentration. Above a threshold concentration of the adsorbing solution (50 microg/mL) an interconnected network of the FNIII(7-10) fragment is obtained on the material surface. The bioavailability of specific cell adhesion domains, including RGD, within the molecules was higher on PEA than on the control glass. The biological activity of the fragment was further investigated by evaluating focal adhesion formation and actin cytoskeleton for MC3T3-E1 osteoblast-like cells. Well-developed focal adhesion complexes and insertions of actin stress fibers were found on PEA in a similar way as it happens in the control SAM-OH. Moreover, increasing the hydrophilicity of the surface by incorporating -OH groups led to globular molecules of the fragment homogeneously distributed throughout the surface; and the cell-material interaction is reduced as depicted by the lack of well-developed focal plaques and actin cytoskeleton.


High performance field-effect transistor based on multilayer tungsten disulfide.
Semiconducting two-dimensional transition metal chalcogenide crystals have been regarded as the promising candidate for the future generation of transistor in modern electronics. However, how to fabricate those crystals into practical devices with acceptable performance still remains as a challenge. Employing tungsten disulfide multilayer thin crystals, we demonstrate that using gold as the only contact metal and choosing appropriate thickness of the crystal, high performance transistor with on/off ratio of 10(8) and mobility up to 234 cm(2) V(-1) s(-1) at room temperature can be realized in a simple device structure. Furthermore, low temperature study revealed that the high performance of our device is caused by the minimized Schottky barrier at the contact and the existence of a shallow impurity level around 80 meV right below the conduction band edge. From the analysis on temperature dependence of field-effect mobility, we conclude that strongly suppressed phonon scattering and relatively low charge impurity density are the key factors leading to the high mobility of our tungsten disulfide devices.


Self-bonded composite films based on cellulose nanofibers and chitin nanocrystals as antifungal materials.
Cellulose nanofibers and chitin nanocrystals, two main components of agricultural and aquacultural by-products, were obtained from blue agave and yellow squat lobster industrial residues. Cellulose nanofibers were obtained using high pressure homogenization, while chitin nanocrystals were obtained by hydrolysis in acid medium. Cellulose nanofibers and chitin nanocrystals were characterized by X-ray diffraction, Atomic Force Microscopy and Infrared spectroscopy. Self-bonded composite films with different composition were fabricated by hot pressing and their properties were evaluated. Antifungal activity of chitin nanocrystals was studied using a Cellometer(®) cell count device, mechanical properties at tension were measured with a universal testing machine, water vapor permeability was evaluated with a thermohygrometer and surface tension with sessile drop contact angle method. The addition of chitin nanocrystals reduced slightly the mechanical properties of the composite. Presence of chitin nanocrystals influenced the growth of Aspergillus sp fungus in the surface of the composites as expected.


Isolation and uptake characteristics of human cell variants resistant to the antiproliferative effects of methylglyoxal bis(guanylhydrazone).
Four variants (VA2/MGBG) of the human cell line, VA2, have been isolated which are 10- to 20-fold more resistant than the parent line to the antiproliferative effects of the anticancer agent, methylglyoxal bis(guanylhydrazone) (MGBG). Drug resistance was not cytoplasmically transmitted by cytoplast cell fusion for any of the four sublines, suggesting that the genes responsible for resistance may be of nuclear rather than mitochondrial origin. Uptake properties were characterized in the VA2 cells and two of the four variant lines. Uptake of [14C]MGBG during long-term (0.5 to 28 hr) incubations was 3 to 4 times greater in the VA2 cells than in the VA2/MGBG sublines. However, during short-term (2 to 60 min) incubations, the uptake of [14C]MGBG or [3H]spermidine (which competes for MGBG uptake) was similar for all cell lines. This was further supported by kinetic data which indicated that, for [14C]MGBG uptake at 4 min, the apparent Km for all cell lines was 5.8 to 13.4 microM, and the Vmax, 44 to 53 pmol/mg/min. For [3H]spermidine uptake, the apparent Km values were approximately 1 microM and Vmax, 54 to 69 pmol/mg/min. Efflux studies performed on cells incubated for 30 min in 10 microM [14C]MGBG revealed that the two VA2/MGBG sublines released drug much more rapidly than did VA2 cells over an 8-hr period. Thus, while the variants may transport MGBG at a rate similar to VA2 cells, the drug is not accumulated to the same extent during long-term incubations, probably because of altered intracellular binding sites for MGBG. The identification of these sites may provide insight into the basis for antiproliferative action of MGBG.


Robotic DNA Nanostructures.
Over the past decade, DNA nanotechnology has spawned a broad variety of functional nanostructures tailored toward the enabled state at which applications are coming increasingly in view. One of the branches of these applications is in synthetic biology, where the intrinsic programmability of the DNA nanostructures may pave the way for smart task-specific molecular robotics. In brief, the synthesis of the user-defined artificial DNA nano-objects is based on employing DNA molecules with custom lengths and sequences as building materials that predictably assemble together by obeying Watson-Crick base pairing rules. The general workflow of creating DNA nanoshapes is getting more and more straightforward, and some objects can be designed automatically from the top down. The versatile DNA nano-objects can serve as synthetic tools at the interface with biology, for example, in therapeutics and diagnostics as dynamic logic-gated nanopills, light-, pH-, and thermally driven devices. Such diverse apparatuses can also serve as optical polarizers, sensors and capsules, autonomous cargo-sorting robots, rotary machines, precision measurement tools, as well as electric and magnetic-field directed robotic arms. In this review, we summarize the recent progress in robotic DNA nanostructures, mechanics, and their various implementations.


Biological mechanisms underlying the role of physical fitness in health and resilience.
Physical fitness, achieved through regular exercise and/or spontaneous physical activity, confers resilience by inducing positive psychological and physiological benefits, blunting stress reactivity, protecting against potentially adverse behavioural and metabolic consequences of stressful events and preventing many chronic diseases. In this review, we discuss the biological mechanisms underlying the beneficial effects of physical fitness on mental and physical health. Physical fitness appears to buffer against stress-related disease owing to its blunting/optimizing effects on hormonal stress responsive systems, such as the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system. This blunting appears to contribute to reduced emotional, physiological and metabolic reactivity as well as increased positive mood and well-being. Another mechanism whereby regular exercise and/or physical fitness may confer resilience is through minimizing excessive inflammation. Chronic psychological stress, physical inactivity and abdominal adiposity have been associated with persistent, systemic, low-grade inflammation and exert adverse effects on mental and physical health. The anti-inflammatory effects of regular exercise/activity can promote behavioural and metabolic resilience, and protect against various chronic diseases associated with systemic inflammation. Moreover, exercise may benefit the brain by enhancing growth factor expression and neural plasticity, thereby contributing to improved mood and cognition. In summary, the mechanisms whereby physical fitness promotes increased resilience and well-being and positive psychological and physical health are diverse and complex.