Thymic Hyperplasia Associated with Graves' Disease: Pathophysiology and Proposed Management Algorithm.
The association between Graves' disease (GD) and thymic hyperplasia (TH) was first described in 1912 and has been reported numerous times thereafter. TH associated with GD presents as an incidental mediastinal mass on chest X-ray or computed tomography (CT). The pathogenesis of TH in the setting of GD is unclear but seems to involve a complex interplay of hormonal and immunological mechanisms. Here, the effect that thyroid hormones and autoimmunity have on thymic growth and size is reviewed. The authors' experience, along with a review of published case reports, reveals that general physicians may be unfamiliar with this association. This lack of familiarity may result in an aggressive management course, including surgical intervention, along with its associated risks and costs. The differential diagnosis and diagnostic workup of thymic enlargement associated with GD is discussed in light of the available clinical evidence. Recent literature confirms the generally benign nature of TH associated with GD, and supports a conservative approach for the diagnostic workup and initial management. Practical management recommendations for thymic enlargement associated with GD have been formulated and are presented here.


Effect of pharmacokinetic sampling methods on aminoglycoside dosing in critically ill surgery patients.
We compared pharmacokinetic parameters derived from three aminoglycoside serum concentration sampling methods and evaluated their effects on recommended aminoglycoside dosing regimens in 60 critically ill surgery patients. Patients had presumed or documented gram-negative sepsis, and had at least 4 aminoglycoside serum concentrations measured. We used a one-compartment model for peak and trough, 3-point series, and 4-point series sampling methods. Dosing regimens were calculated for each patient based on values derived from each method. We found differences in regimens for nearly 50% of patients if either 4- or 3-point series sampling was used to calculate the recommended dosage rather than peak and trough sampling. However, the 3-point method required a clinically significant change in regimen in only 12% of patients compared with 4-point sampling. The variability of all values derived from 3-point sampling were well accounted for by the 4-point method (r2 > 0.80). In addition, we noted significantly greater relative precision for 3-point sampling than peak and trough sampling for estimates of clearance, elimination rate, recommended daily dosage, and recommended dosing frequency. We recommend three optimally timed samples be drawn instead of peak and trough levels in dosing aminoglycosides in critically ill surgery patients.


Development of Educational Communication Path of Journalism in Colleges and Universities in the Era of Mobile Communication.
The development of journalism has a huge impact on mobile communication technology and media ecology. Especially in terms of information dissemination, it not only allows people to better obtain the content they are interested in but also provides media workers with more ways to understand their own needs, meet the needs of audiences, and enhance competitiveness. Therefore, in order to enhance the development space of the journalism major, this article studies the communication development path of this major in colleges and universities in the era of mobile communications. This article mainly uses case analysis method, data method, and investigation method to study the development of journalism education in colleges and universities. The survey results show that 21 people believe that the authenticity of news is an indispensable item in teaching. Therefore, the education and communication development of journalism majors in colleges and universities cannot ignore the principle of authenticity. There are 18 people who think it is necessary to tie their majors with the Internet, indicating that colleges and universities can use the Internet platform to teach journalism.


Design and Discovery of Novel Chiral Antifungal Amides with 2-(2-Oxazolinyl)aniline as a Promising Pharmacophore.
Inspired by established succinate dehydrogenase inhibitors (SDHIs), our continuing efforts toward the discovery of chiral antifungal amides turned to the optimization of their polar regions with 2-(2-oxazolinyl)aniline as a known pharmacophore. Scaffold hopping and bioactivity-guided convergent synthesis enabled the identification of promising antifungal categories. Fine tuning of the substituents and chirality furnished seven amides (1s, 1t, 2d, 2h, 2j, 3k, and 2l) as antifungal candidates, with EC50 values lower than 5 mg/L. The first investigation of chiral amides of acyclic acids as SDHIs was conducted, and compound 2d was selected as a promising candidate against Botrytis cinerea, with a preventative efficacy of up to 93.9% at 50 mg/L, which is better than that of boscalid. The different binding models between compounds with different configurations were simulated for compound 2d and its diastereoisomers. The benefits of synthetic accessibility and cost-effectiveness highlight the practical potential for compound 2d as a good alternative to known SDHI fungicides.


Properties, promotive and obstructive conditions of multi-professional teaching and learning of health professions and non-health professions: an explorative survey from the perspective of teachers.
Care for people with dementia is considered a multi-professional challenge that requires a collaborative approach between health professionals and non-health professionals. Didactic strategies to ensure the same qualifications across these occupational groups are lacking. This article presents the joint learning of selected properties and promotive and obstructive conditions, using the example of a multi-professional Master's programme. It subsequently draws conclusions for didactic concepts. The perceptions of 12 teachers on this Master's programme, all representing different professions, were determined by using a qualitative exploratory survey on the three stated dimensions. With the aid of a summarising content analysis, their statements were condensed and abstracted so as to deduce appropriate requirements for methodical and didactic learning scenarios. In view of the fact that the students have very varied previous knowledge, the main challenge is finding a balance between expertise and tediousness. Establishing essential and common expertise, as well as sensitivity for different perspectives, is made particularly difficult by the fact that health and non-health professions differ greatly in terms of methods and approaches. For a successful outcome, the content focal points and didactic and methodical concepts for a learning group need to take into account the composition of that specific group. Recourse to didactic standard concepts is only possible to a limited extent. The aim of joint teaching and learning of health and non-health professionals is to enhance the understanding of a profession: This is done by making individuals aware of their role in the chain of care, so they can recognise and organise the mutual conditionality of their own and external professional contributions.


Calculating Intraoperative Fluid Deficit to Prevent Abdominal Compartment Syndrome in Hip Arthroscopy.
Abdominal compartment syndrome (ACS) is a rare but potentially fatal complication that can occur during hip arthroscopy. This usually occurs as a result of arthroscopic fluid passing into the retroperitoneal space through the psoas tunnel. From the retroperitoneal space, the fluid can then enter the intraperitoneal space through defects in the peritoneum. Previous studies have identified female sex, iliopsoas tenotomy, pump pressure, and operative time as potential risk factors for fluid extravasation. We present a method to measure intraoperative fluid deficit during hip arthroscopy to alert surgeons to possible ACS. Our proposed technique requires diligent intraoperative monitoring of fluid output through various suction devices, including suction canisters, puddle vacuums, and suction mats. The difference is then calculated from the fluid intake from the arthroscopic fluid bags. If the difference is greater than 1500 mL, then the anesthesiologist and circulating nurse are instructed to examine the abdomen for distension every 15 minutes. This, combined with other common symptoms such as hypotension and hypothermia, should alert the surgical team to the development of ACS. Despite limitations to this technique, this approach offers an objective method to calculate intra-abdominal fluid extravasation.


Preparation of Purified Gram-positive Bacterial Cell Wall and Detection in Placenta and Fetal Tissues.
Cell wall is a complex biopolymer on the surface of all Gram-positive bacteria. During infection, cell wall is recognized by the innate immune receptor Toll-like receptor 2 causing intense inflammation and tissue damage. In animal models, cell wall traffics from the blood stream to many organs in the body, including brain, heart, placenta and fetus. This protocol describes how to prepare purified cell wall from Streptococcus pneumoniae, detect its distribution in animal tissues, and study the tissue response using the placenta and fetal brain as examples.


[Application of bowel plication combined with early enteral nutrition in the enhanced recovery after surgery for neonates with jejunal atresia].
To evaluate the efficacy of bowel plication combined with early enteral nutrition (EEN) in the enhanced recovery after surgery(ERAS) of jejunal atresia (JA) neonates. Between January 2005 and January 2014, 58 neonates with JA underwent surgical treatment in Children's Hospital of Nanjing Medical University. Their clinical data, including operation procedures, ages, birth weight, concomitant diseases, age at surgery, hospital stay, total parenteral nutrition (TPN), postoperative intestinal function recovery (the time to the first oral feeding and the time to oral feeding volume reaching 150 ml·kg-1·d-1), complications and reoperation, were retrospectively analyzed. According to the surgical procedures, the 58 neonates were divided into three groups: control group(18 cases, undergoing atretic segments resection and primary anastomosis), bowel plication group(19 cases, undergoing bowel plication after atretic segments resection and primary anastomosis) and bowel plication combined with EEN group (21 cases, undergoing bowel plication combined with EEN). No significant differences of ages, birth weight, age at operation, and concomitant diseases were found among 3 groups (all P>0.05). The time of hospital stay, the time to the first oral feeding, the time to oral feeding volume reaching 150 ml·kg-1·d-1, and the time of TPN in bowel plication group were significantly shorter than those of control group [(19.3±4.4) d vs. (22.7±3.1) d, t=2.696, P=0.011; (9.8±3.3) d vs. (12.5±3.0) d, t=2.630, P=0.013; (18.5±4.1) d vs. (21.5±2.5) d, t=2.726, P=0.011; (13.1±2.9) d vs. (15.0±2.3) d, t=2.219, P=0.033]. However, above parameters of bowel plication combined with EEN group were significantly shorter than those of bowel plication group [(15.3±3.5) d vs. (19.3±4.4), t=4.120, P=0.003; (7.7±2.2) d vs. (9.8±3.3) d, t=2.428, P=0.020; (14.8±2.5) d vs. (18.5±4.1) d, t=3.752, P=0.001; (9.5±3.0) vs. (13.1±2.9) d, t=4.370, P=0.000]. The bowel plication combined with EEN contributes to the early use of intestinal function, shorten the time to the first oral feeding, and reduces the use of TPN, which can improve the recovery of jejunal atresia neonates.


Quasi-Freestanding Bilayer Borophene on Ag(111).
The lattice structure of monolayer borophene depends sensitively on the substrate yet is metallic independent of the environment. Here, we show that bilayer borophene on Ag(111) shares the same ground state as its freestanding counterpart that becomes semiconducting with an indirect bandgap of 1.13 eV, as evidenced by an extensive structural search based on first-principles calculations. The bilayer structure is composed of two covalently bonded v1/12 boron monolayers that are stacked in an AB mode. The interlayer bonds not only localize electronic states that are otherwise metallic in monolayer borophene but also in part decouple the whole bilayer from the substrate, resulting in a quasi-freestanding system. More relevant is that the predicted bilayer model of a global minimum agrees well with recently synthesized bilayer borophene on Ag(111) in terms of lattice constant, topography, and moiré pattern.


Activation of blood neutrophils in acute episodes of farmer's lung.
Farmer's lung often presents clinically as recurring acute episodes several hours after exposure to moldy hay. During these episodes the blood neutrophil count increases. Because activated neutrophils release toxic oxygen metabolites and proteinases, we hypothesized that the pulmonary reaction in farmer's lung may be induced by the secretory products of activated neutrophils. To evaluate this concept, we quantified the respiratory burst of separated blood neutrophils from patients with farmer's lung (n = 12) during standardized exposure tests with moldy hay. The respiratory burst of these cells was evaluated by measuring zymosan-stimulated and lucigenin-amplified chemiluminescence (CL). Asymptomatic farmers (n = 12) and normal volunteers with no prior exposure to moldy hay (n = 15) were used as control subjects. As expected, following exposure in the group of patients with farmer's lung, striking changes in VC, TLCO, and PaO2 were observed, whereas there were only minor changes in these parameters in both control groups. In all three groups a considerable increase in the blood leukocyte count was observed. The CL response of the blood neutrophils from patients with farmer's lung 6 h after exposure was significantly higher than before or 1 h after exposure (p < 0.05 for both comparisons), whereas there was no significant change in the CL response in either control group during the observation period. Our results indicate that antigen inhalation induces an increase in the number of circulating neutrophils in patients and controls, but in patients with an acute episode of farmer's lung the neutrophils are primed for an enhanced respiratory burst and may thereby damage the lung.


Pharmacological characterization of memoquin, a multi-target compound for the treatment of Alzheimer's disease.
Alzheimer's disease (AD) is characterized by progressive loss of cognitive function, dementia and altered behavior. Over 30 million people worldwide suffer from AD and available therapies are still palliative rather than curative. Recently, Memoquin (MQ), a quinone-bearing polyamine compound, has emerged as a promising anti-AD lead candidate, mainly thanks to its multi-target profile. MQ acts as an acetylcholinesterase and β-secretase-1 inhibitor, and also possesses anti-amyloid and anti-oxidant properties. Despite this potential interest, in vivo behavioral studies with MQ have been limited. Here, we report on in vivo studies with MQ (acute and sub-chronic treatments; 7-15 mg/kg per os) carried out using two different mouse models: i) scopolamine- and ii) beta-amyloid peptide- (Aβ-) induced amnesia. Several aspects related to memory were examined using the T-maze, the Morris water maze, the novel object recognition, and the passive avoidance tasks. At the dose of 15 mg/kg, MQ was able to rescue all tested aspects of cognitive impairment including spatial, episodic, aversive, short and long-term memory in both scopolamine- and Aβ-induced amnesia models. Furthermore, when tested in primary cortical neurons, MQ was able to fully prevent the Aβ-induced neurotoxicity mediated by oxidative stress. The results support the effectiveness of MQ as a cognitive enhancer, and highlight the value of a multi-target strategy to address the complex nature of cognitive dysfunction in AD.


Association Between Temporomandibular Disorders Pain and Migraine: Results of the Health 2000 Survey.
To study the possible associations of various clinically assessed painful signs of temporomandibular disorders (TMD) with the presence of migraine using a large population-based dataset. The data were taken from the nationally representative Health 2000 Survey (BRIF8901). The sample consisted of 5,876 adults (age range 30 to 97 years, mean ± standard deviation 52.5 ± 14.8), 5,378 nonmigraineurs and 498 migraineurs. The study participants answered questions concerning migraine presence, migraine frequency, and migraine medication consumption during a home interview. They also underwent a clinical TMD examination. Based on the multivariate regression models, painful muscular TMD, but not joint-related TMD, was associated with the presence of migraine (odds ratio [OR] = 1.58; 95% confidence interval [CI] = 1.23 to 2.04; P < .01). Migraine with TMD was associated with increased migraine frequency (daily or a few attacks within a week) (OR = 1.93; 95% CI = 1.27 to 2.93; P < .01) and higher migraine medication consumption (OR = 2.37; 95% CI = 1.43 to 3.92; P < .01). According to the results of this study, muscle-related TMD pain is associated with the presence of migraine. Additionally, migraine along with painful TMD signs is associated with increased migraine frequency and migraine medication consumption.


The prevalence of oro-facial barotrauma among scuba divers.
Barotrauma is a physical injury that results from ambient pressure changes during flying, diving or hyperbaric oxygen therapy. The aim of this study was to assess the prevalence of oro-facial barotrauma among a sample of scuba divers in Jeddah, Saudi Arabia. Data for the study were collected through a self-reported questionnaire that was distributed to 166 divers. The questionnaire was divided into two parts, in which the first part contained demographic data and the second part consists of multiple choice questions and a few open-ended questions discussing the different signs and symptoms of orofacial barotraumas. One-hundred-and-sixty-three divers responded. The most frequent symptoms during diving were dry mouth (51.9%), followed by clenching (32.5%) and temporomandibular joint (TMJ) pain (19.5%), while the most frequent symptoms after diving were dry mouth (22.7%) followed by clenching and facial pain (16.9%). Clenching and dry mouth were common findings but are temporary in nature and do not warrant any dental intervention. TMJ and facial pain were also reported but were temporary. The use of commercial mouthpieces during diving may be related to more symptoms when compared with customized types.


Carvedilol can attenuate histamine-induced paw edema and formaldehyde-induced arthritis in rats without risk of gastric irritation.
Rheumatoid arthritis treatment aims to control joint damage and any associated complications such as cardiovascular disease. Most anti-inflammatory drugs have a high tendency to cause gastro-intestinal irritation. The present study is designed to investigate the anti-inflammatory effect of carvedilol and to study its effect on gastric mucosa. Lornoxicam (1.3mg/kg) or carvedilol (10mg/kg) was administrated orally 1h before histamine injection into animals of a histamine-induced paw edema model and orally daily for 11days into animals of a formaldehyde-induced arthritis model. Tumor necrosis factor-α and prostaglandin E2 were measured in animals of the formaldehyde-induced arthritis model. The effect of lornoxicam and carvedilol on gastric mucosa was assessed in normal rats and after induction of cold stress ulcer. Carvedilol succeeded in reducing hind paw edema in both histamine-induced paw edema and formaldehyde-induced arthritis and in reducing the elevated level of tumor necrosis factor-α and prostaglandin E2 nearly with near equal efficacy compared with lornoxicam. Carvedilol did not show any ulcerative effect on the gastric mucosa of normal rats, and its use was associated with an improvement of both the gross and histopathological pictures of gastric ulcers in animals of the cold stress ulcer model compared with lornoxicam treated rats. The current findings support the use of carvedilol both in the management of inflammation as well as the prevention of cardiovascular complications in rheumatoid arthritis patients. The use of carvedilol was not associated with any gastro-intestinal tract irritation.


A volume-displacement plethysmograph to measure limb blood flow in the newborn infant.
An instrument is described that measures limb blood flow in newborn infants by venous occlusion plethysmography. The plethysmograph is filled with air and a pneumotachygraph measures the volume displaced during venous occlusion. The response of the system is linear for flows over the range 1 to 100 ml/min and the frequency response to a square wave pressure change is 22 Hz with a 95% response time of 0.5 second. The average flow in the forearm of 10 normal newborn infants was 5.9 ml/min per 100 ml of tissue.


Beyond Explicit Codebook Generation: Visual Representation Using Implicitly Transferred Codebooks.
The bag-of-visual-words model plays a very important role for visual applications. Local features are first extracted and then encoded to get the histogram-based image representation. To encode local features, a proper codebook is needed. Usually, the codebook has to be generated for each data set which means the codebook is data set dependent. Besides, the codebook may be biased when we only have a limited number of training images. Moreover, the codebook has to be pre-learned which cannot be updated quickly, especially when applied for online visual applications. To solve the problems mentioned above, in this paper, we propose a novel implicit codebook transfer method for visual representation. Instead of explicitly generating the codebook for the new data set, we try to make use of pre-learned codebooks using non-linear transfer. This is achieved by transferring the pre-learned codebooks with non-linear transformation and use them to reconstruct local features with sparsity constraints. The codebook does not need to be explicitly generated but can be implicitly transferred. In this way, we are able to make use of pre-learned codebooks for new visual applications by implicitly learning the codebook and the corresponding encoding parameters for image representation. We apply the proposed method for image classification and evaluate the performance on several public image data sets. Experimental results demonstrate the effectiveness and efficiency of the proposed method.


Metamorphic Proteins: Emergence of Dual Protein Folds from One Primary Sequence.
Every amino acid exhibits a different propensity for distinct structural conformations. Hence, decoding how the primary amino acid sequence undergoes the transition to a defined secondary structure and its final three-dimensional fold is presently considered predictable with reasonable certainty. However, protein sequences that defy the first principles of secondary structure prediction (they attain two different folds) have recently been discovered. Such proteins, aptly named metamorphic proteins, decrease the conformational constraint by increasing flexibility in the secondary structure and thereby result in efficient functionality. In this review, we discuss the major factors driving the conformational switch related both to protein sequence and to structure using illustrative examples. We discuss the concept of an evolutionary transition in sequence and structure, the functional impact of the tertiary fold, and the pressure of intrinsic and external factors that give rise to metamorphic proteins. We mainly focus on the major components of protein architecture, namely, the α-helix and β-sheet segments, which are involved in conformational switching within the same or highly similar sequences. These chameleonic sequences are widespread in both cytosolic and membrane proteins, and these folds are equally important for protein structure and function. We discuss the implications of metamorphic proteins and chameleonic peptide sequences in de novo peptide design.


Marital quality, marital disruption, and immune function.
Marital disruption is associated with significant increases in a variety of psychologic and physical disorders. In order to examine psychologic and physiologic mediators, self-report data and blood samples were obtained from 38 married women and 38 separated/divorced women. Among married subjects, poorer marital quality was associated with greater depression and a poorer response on three qualitative measures of immune function. Women who had been separated 1 year or less had significantly poorer qualitative and quantitative immune function than their sociodemographically matched married counterparts. Among the separated/divorced cohort, shorter separation periods and greater attachment to the (ex)husband were associated with poorer immune function and greater depression. These data are consistent with epidemiologic evidence linking marital disruption with increased morbidity and mortality.


Travelling models and the challenge of pragmatic contexts and practical norms: the case of maternal health.
As in other areas of international development, we are witnessing the proliferation of 'traveling models' developed by international experts and introduced in an almost identical format across numerous countries to improve some aspect of maternal health systems in low- and middle-income countries. These policies and protocols are based on 'miracle mechanisms' that have been taken out of their original context but are believed to be intrinsically effective in light of their operational devices.In reality, standardised interventions are, in Africa and elsewhere, confronted with pragmatic implementation contexts that are always varied and specific, and which lead to drifts, distortions, dismemberments and bypasses. The partogram, focused antenatal care, the prevention of mother-to-child transmission of HIV or performance-based payment all illustrate these implementation gaps, often caused by the routine behaviour of health personnel who follow practical norms (and a professional culture) that are often distinct from official norms - as is the case with midwives.Experiences in maternal and child health in Africa suggest that an alternative approach would be to start with the daily reality of social and practical norms instead of relying on models, and to promote innovations that emerge from within local health systems.


Trends in total knee arthroplasty.
The success of total knee arthroplasty (TKA) over the past two decades of use has resulted in the implantation of TKA into younger patients who have increased functional requirements and demand increased implant longevity. Improved functional performance requires enhanced range of motion, increased motor performance, and creation of kinematic patterns that more closely resemble the normal knee. Increased longevity necessitates more durable implant fixation, improvements in bearing materials, and lower polyethylene stresses. Considerations to reduce polyethylene wear include increased cross-linking, improved femoral component surface finish, better modular tibial locking mechanisms, and the use of mobile-bearing TKA designs that allow increased implant conformity and reduced contact stresses without increasing loads transmitted to the fixation interface.


Inflammation-induced reactive nitrogen species cause proteasomal degradation of dimeric peroxiredoxin-1 in a mouse macrophage cell line.
Peroxiredoxin 1 (PRDX1) is an antioxidant enzyme that, when secreted, can act as a proinflammatory signal. Here we studied the regulation of intracellular PRDX1 by lipopolysaccharide (LPS) and interferon-gamma (IFN-γ) in the RAW 264.7 mouse macrophage cell line. While LPS or IFN-γ alone did not affect PRDX1 protein levels, their combination led to an almost complete loss of the PRDX1 dimer. This was likely mediated by the increased production of nitric oxide (NO) as it was reversed by the NO synthase inhibitor L-N-methylarginine (L-NMMA), while a NO-releasing agent decreased PRDX1 levels. Inhibition of the proteasome with MG132 also prevented the loss of the PRDX1 dimer, suggesting that the decrease is due to a NO-activated proteasomal degradation pathway. By contrast with the decrease in protein levels, LPS increased PRDX1 mRNA and this effect was amplified by IFN-γ. Two other Nrf2 target genes, thioredoxin reductase (TXNRD1) and haem oxygenase (HMOX1), were also induced by LPS but IFN-γ did not increase their expression further. This study shows that inflammation differentially regulates PRDX1 at the levels of protein stability and gene expression, and that NO plays a key role in this mechanism.


Lipid profile disturbances may predispose psoriatic patients to liver dysfunction.
Psoriasis is a chronic inflammatory disease associated with metabolic disturbances and liver dysfunction. Both serum fatty acids (FA) and ceramides (Cer) have structural functions but also are signal molecules that could be involved in the pathogenesis of liver dysfunction. To assess the concentration of the circulating FA and Cer in correlation with the alanine aminotransferase (ALT) blood level in psoriatic patients. In addition, we have examined the relationship between ALT concentration and severity of the disease and inflammation markers. Eighty-five patients with psoriasis and 32 healthy controls were enrolled in the study. Patients were divided into 2 groups according to ALT blood levels. Serum concentration of 14 FA and 14 Cer were measured by gas-liquid chromatography. The results were correlated with the Psoriasis Area and Severity Index (PASI), serum lipid profile, and inflammatory markers. We observed higher PASI score (p = 0.01) and higher C-reactive protein (p = 0.02) concentration in the group of psoriatic patients with high ALT. Serum ALT positively correlated with saturated fatty acids (SFA) (p = 0.01, r = 0.27) and SFA/unsaturated fatty acids (UFA) ratio (p = 0.01, r = 0.26). ALT negatively correlated with UFA level (p = 0.008, r = -0.28). Lignoceric ceramide positively correlated with ALT level (r = 0.22; p = 0.045) in psoriatic patients. Patients with severe psoriasis are predisposed to the development of liver dysfunction. We have demonstrated disturbances of serum fatty acid and sphingolipid profile in psoriatic patients, which may trigger liver disease.


Acyclovir resistant genital herpes virus infection in a patient with AIDS.
Three acyclovir resistant strains of HSV-2 were isolated from mucoulcerative lesions in a patient suffering from AIDS in whom the oral and intravenous acyclovir treatment was unsuccessful. All the isolates were classified by monoclonal antibodies and showed no differences in DNA restriction patterns.


Phytoestrogens in the management of the menopause: up-to-date.
Despite the benefits of conventional hormone replacement therapy, some women are not candidates for this treatment and many others choose not to take it. As a result, there is growing interest among patients about natural alternatives. There is some evidence that phytoestrogens may offer protection against a wide range of human conditions, including breast cancer, cardiovascular disease, brain dysfunction, osteoporosis, and menopausal symptoms. The literature on the possible health benefits of phytoestrogens has expanded exponentially since the 1980s, mainly in response to funding initiatives by the U.S. government and soybean industries, and more lately by European and UK Ministries of Food. The physiological effects of phytoestrogens also have created a marketing opportunity that has been used by industry, particularly in soybean-producing countries such as the U.S. and Australia. Nevertheless, clinical applications for phytoestrogens are still in their infancy, and more interventional trials are required to reach definitive conclusions regarding their efficacy and safety, although they appear to represent a promising group of compounds, which may be useful in the future for the treatment of the menopausal syndrome. Also, the lack of clinical data presently available must signal caution in relation to the possible risk of adverse effects. Obstetricians and Gynecologists, Family Physicians. After completion of this article, the reader will be able to identify the various types of phytoestrogens, list the sources of phytoestrogens, and summarize the various effects of phytoestrogens.


Alpha2-adrenoceptor agonists trigger prolactin signaling in breast cancer cells.
Breast cancer is the most frequent malignancy among women worldwide. We have described the expression of α2-adrenoceptors in breast cancer cell lines, associated with increased cell proliferation and tumor growth. A mitogenic autocrine/paracrine loop of prolactin (Prl) has been described in breast cancer cells. We hypothesized that the α2-adrenergic enhancement of proliferation could be mediated, at least in part, by this Prl loop. In both T47D and MCF-7 cell lines, the incubation with the α2-adrenergic agonist dexmedetomidine significantly increased Prl release into the culture medium (measured by the Nb2 bioassay), this effect being reversed by the α2-adrenergic antagonist rauwolscine. No change in Prl receptors (PrlR) was observed by RT-qPCR in these cell lines. In IBH-6 cells a decrease in Prl secretion was observed at the lower dexmedetomidine concentration. The signaling pathways involved in ovine Prl (oPrl) and dexmedetomidine action were also assessed. Both compounds significantly activated STAT5 and ERK in all three cell lines. In T47D and MCF-7 cell lines also AKT was activated by both Prl and dexmedetomidine. We therefore describe the STAT5 phosphorylation by an α2-adrenergic agonist, dexmedetomidine. In T47D cells, the α2-adrenergic stimulation of cell proliferation is probably mediated, at least in part, by the Prl autocrine/paracrine loop, because this effect is abrogated by the specific PrlR antagonist Δ1-9-G129R-hPrl. The implication of Prl loop describes a novel mechanism of action of this GPCR.


Nutrition Screening vs Nutrition Assessment: What's the Difference?
Screening and assessment imply different processes, with the former indicating risk factors for a deprived nutrition condition and the latter providing the nutrition diagnosis. Both should be routinely performed at hospital admission according to recommended guidelines; however, this is not the reality worldwide, and undernutrition remains highly prevalent in the hospital setting. Therefore, the objective of the current review is to delve into the principles leading to nutrition status deficiencies and how they should be addressed by screening and assessment. A critical appraisal for the reasons associated with the misunderstanding between screening and assessing is proposed without further discussing the many available screening tools while approaching some of the assessment instruments.


Minimal Invasive Cystometry and Intra-Abdominal Pressure Assessments in Rodents: A Novel Animal Study.
BACKGROUND The abdominal straining pattern can act as a novel parameter for improving the prediction of bladder outlet obstruction (BOO). To preserve detrusor function in the early stage of urinary system impairment, such as BOO, we establish a novel method for cystometry and Intra-abdominal pressure (IAP) assessments in rodents without cystostomy. MATERIAL AND METHODS Twenty mice and rats were divided into three groups (control, sham-operated and BOO group) respectively. The cystometry and IAP assessments were measured by the pediatric venous indwelling sheath and coronary dilatation catheter connected to Laborie urodynamic system on postoperative day 7. Data was collected simultaneously through urethra and rectum in each group. In addition, bladder histology was assessed to confirm BOO. RESULTS The novel method can collect the urodynamic parameters successfully, including the BLPP, IAP, MBC, etc. IAP was elevated in BOO rats, but no significantly difference was found between the sham-operated rats and the control rats. The hypertrophy of detrusor muscle in bladder section was observed by Masson trichrome staining in BOO group compared with other groups. CONCLUSIONS Our novel method based on innovative research implement for cystometry and IAP assessments in rodents is a reliable and replicable approach for evaluating the lower urinary tract function. Especially it provides detailed information to evaluate lower urinary tract structures and function in the early stage of BOO.


Reduced Dual-Task Performance in MS Patients Is Further Decreased by Muscle Fatigue.
Multiple sclerosis (MS) can be accompanied by motor, cognitive, and sensory impairments. Additionally, MS patients often report fatigue as one of their most debilitating symptoms. It is, therefore, expected that MS patients will have difficulties in performing cognitive-motor dual tasks (DTs), especially in a fatiguing condition. To determine whether MS patients are more challenged by a DT than controls in a fatiguing and less-fatiguing condition and whether DT performance is associated with perceived fatigue. A group of 19 MS patients and 19 age-, sex-, and education-matched controls performed a cognitive task (2-choice reaction time task) separately or concurrent with a low-force or a high-force motor task (index finger abduction at 10% or 30% maximal voluntary contraction). MS patients performed less well on a cognitive task than controls. Cognitive task performance under DT conditions decreased more for MS patients. Moreover, under high-force DT conditions, cognitive performance declined in both groups but to a larger degree for MS patients. Besides a decline in cognitive task performance, MS patients also showed a stronger decrease in motor performance under high-force DT conditions. DT costs were positively related to perceived fatigue as measured by questionnaires. Compared with controls, MS patients performed less well on DTs as demonstrated by a reduction in both cognitive and motor performances. This performance decrease was stronger under fatiguing conditions and was related to the sense of fatigue of MS patients. These data illustrate problems that MS patients may encounter in daily life because of their fatigue.


[Effect of hepatectomy on liver adenylate cyclase activity in rats of various ages].
Age-dependent differences were found in patterns of rat liver adenylate cyclase system in response to hepatectomy-induced proliferation. After hepatectomy a decrease in basic activity of adenylate cyclase and in content of cAMP were observed only in adult animals. At the same time, the epinephrine-stimulated enzymatic activity was decreased in old hepatectomized rats as compared with intact animals. These alterations in regulatory activity of the adenylate cyclase system appear to affect the intensity of DNA biosynthesis and the functional activity of regenerating liver tissue of old rats.


Tunable Rashba spin-orbit interaction at oxide interfaces.
The quasi-two-dimensional electron gas found at the LaAlO{3}/SrTiO{3} interface offers exciting new functionalities, such as tunable superconductivity, and has been proposed as a new nanoelectronics fabrication platform. Here we lay out a new example of an electronic property arising from the interfacial breaking of inversion symmetry, namely, a large Rashba spin-orbit interaction, whose magnitude can be modulated by the application of an external electric field. By means of magnetotransport experiments we explore the evolution of the spin-orbit coupling across the phase diagram of the system. We uncover a steep rise in Rashba interaction occurring around the doping level where a quantum critical point separates the insulating and superconducting ground states of the system.


Acute asthma in pregnancy.
To provide an overview on the interrelationship between asthma and pregnancy, focusing on management of pregnant women presenting with an acute severe exacerbation. A review of the current English-language published clinical trials was performed based on MEDLINE search using the Medical Subject Headings pregnancy and asthma. Current reviews on the topic and practice guidelines were also reviewed. Asthma is the most common medical condition to complicate pregnancy, and episodes of acute asthma requiring emergency department visits or hospitalization have been reported in 9-11% of pregnant women managed by asthma specialists. Pregnancy can affect the course of asthma, and the risk of asthma exacerbations requiring intervention in pregnant women is higher than in nonpregnant women. Similarly, asthma can affect pregnancy outcomes. Maternal inflammatory pathways may contribute to the poor pregnancy outcomes, especially in women with uncontrolled asthma. Although data on the effects of maternal asthma on pregnancy have been conflicting, mainly because many published studies have not corrected for asthma severity, it has generally been observed that poorly managed asthma during pregnancy is associated with a higher risk of preterm delivery, low birth weight, and complications such as preeclampsia. Optimal therapy of asthma has been shown to contribute to improved maternal and fetal outcomes. Asthma can complicate the course of pregnancy, and pregnancy can worsen asthma control in some women. Optimal management of asthma during pregnancy is key in ensuring the safety of the mother and the fetus.


Self-crosslinked keratin nanoparticles for pH and GSH dual responsive drug carriers.
Nano-drug delivery system (NDDS) has attracted widespread attention for their controlled drug release. In this work, keratin nanoparticles (KNPs) were prepared by self-crosslinking. No toxic chemical crosslinkers were added in the whole procedure. The morphology and size of KNPs were tested by transmission electron microscopy (TEM) and dynamic light scattering (DLS), respectively. The KNPs exhibited GSH and pH dual responsiveness as well as charge conversion, which were beneficial to tumor therapy. In addition, the anticancer drug of doxorubicin (DOX) could be loaded on KNPs by hydrophobicity and hydrogen bonds. The drug-loaded keratin nanoparticles (KDNPs) accelerated drug release under mimicked tumor microenvironments. In addition, KDNPs could effectively inhibit tumor cell growth while performing low toxicity on normal cells. Moreover, KDNPs could be uptaken by tumor cells through endocytosis. Based on the results, keratin-based nanoparticles were suitable candidates for drug microcarriers.


Psychosocial implications of living with familial risk of a psychiatric disorder and attitudes to psychiatric genetic testing: A systematic review of the literature.
The aim of this systematic review was to synthesize the existing evidence documenting the psychosocial implications of living with a familial risk of an adult-onset psychiatric disorder. Six databases were searched systematically to identify qualitative and quantitative studies, which explored perspectives of those at increased risk for psychiatric disorders, as well as the general public. Thematic analysis was used to identify major themes. Thirty-five articles met the eligibility criteria and reported on the views of 4,896 participants. The literature demonstrates strong interest in psychiatric genetic testing of adults as well as children, whereas attitudes toward prenatal testing were much less positive. Predictors of interest in testing, as well as perceived advantages and disadvantages were identified. Very few studies are available on anticipated and actual reactions to receiving results. Studies show that the majority of participants feel that having a genetic explanation would alleviate some of the stigma associated with mental illness. This review shows that interest in, and predictors of attitudes toward, psychiatric genetic testing are well researched, but the extent to which attitudes will translate into actual testing uptake is unknown. Future research also needs to assess the actual behavioral and psychological impact of genetic testing.


Spatiotemporal vector pulse shaping of femtosecond laser pulses with a multi-pass two-dimensional spatial light modulator.
A novel non-interferometric vector pulse-shaping scheme is developed for femtosecond laser pulses using a two-dimensional spatial light modulator (2D-SLM). By utilizing spatiotemporal pulse shaping obtainable by the 2D-SLM, we demonstrate spatiotemporal vector pulse shaping for the first time.


Specific protein markers for stem cell cross-talk with neighboring cells in the environment.
A stem cell interacts with the neighboring cells in its environment. To maintain a living organism's metabolism, either cell-cell or cell-environment interactions may be significant. Usually, these cells communicate with each other through biological signaling by interactive behaviors of primary proteins or complementary chemicals. The signaling intermediates offer the stem cell's functionality on its metabolism. With the rapid advent of omics technologies, various specific markers by which stem cells cooperate with their surroundings have been discovered and established. In this article, we review several stem cell markers used to communicate with either cancer or immune cells in the human body.


Kaplan-Meier Meets Chemical Kinetics: Intrinsic Rate of SOD1 Amyloidogenesis Decreased by Subset of ALS Mutations and Cannot Fully Explain Age of Disease Onset.
Over 150 mutations in SOD1 (superoxide dismutase-1) cause amyotrophic lateral sclerosis (ALS), presumably by accelerating SOD1 amyloidogenesis. Like many nucleation processes, SOD1 fibrillization is stochastic (in vitro), which inhibits the determination of aggregation rates (and obscures whether rates correlate with patient phenotypes). Here, we diverged from classical chemical kinetics and used Kaplan-Meier estimators to quantify the probability of apo-SOD1 fibrillization (in vitro) from ∼103 replicate amyloid assays of wild-type (WT) SOD1 and nine ALS variants. The probability of apo-SOD1 fibrillization (expressed as a Hazard ratio) is increased by certain ALS-linked SOD1 mutations but is decreased or remains unchanged by other mutations. Despite this diversity, Hazard ratios of fibrillization correlated linearly with (and for three mutants, approximately equaled) Hazard ratios of patient survival (R2 = 0.67; Pearson's r = 0.82). No correlation exists between Hazard ratios of fibrillization and age of initial onset of ALS (R2 = 0.09). Thus, Hazard ratios of fibrillization might explain rates of disease progression but not onset. Classical kinetic metrics of fibrillization, i.e., mean lag time and propagation rate, did not correlate as strongly with phenotype (and ALS mutations did not uniformly accelerate mean rate of nucleation or propagation). A strong correlation was found, however, between mean ThT fluorescence at lag time and patient survival (R2 = 0.93); oligomers of SOD1 with weaker fluorescence correlated with shorter survival. This study suggests that SOD1 mutations trigger ALS by altering a property of SOD1 or its oligomers other than the intrinsic rate of amyloid nucleation (e.g., oligomer stability; rates of intercellular propagation; affinity for membrane surfaces; and maturation rate).


Amylases from thermophilic bacteria: structure and function relationship.
Amylases hydrolyze starch to diverse products including dextrins and progressively smaller polymers of glucose units. Thermally stable amylases account for nearly 25% of the enzyme market. This review highlights the structural attributes of the α-amylases from thermophilic bacteria. Heterologous expression of amylases in suitable hosts is discussed in detail. Further, specific value maximization approaches, such as protein engineering and immobilization of the amylases are discussed in order to improve its suitability for varied applications on a commercial scale. The review also takes into account of the immobilization of the amylases on nanomaterials to increase the stability and reusability of the enzymes. The function-based metagenomics would provide opportunities for searching amylases with novel characteristics. The review is expected to explore novel amylases for future potential applications.


Discovery of Heteroaromatic Sulfones As a New Class of Biologically Compatible Thiol-Selective Reagents.
The selective reaction of chemical reagents with reduced protein thiols is critical to biological research. This reaction is utilized to prevent cross-linking of cysteine-containing peptides in common proteomics workflows and is applied widely in discovery and targeted redox investigations of the mechanisms underlying physiological and pathological processes. However, known and commonly used thiol blocking reagents like iodoacetamide, N-ethylmaleimide, and others were found to cross-react with oxidized protein sulfenic acids (-SOH) introducing significant errors in studies employing these reagents. We have investigated and are reporting here a new heteroaromatic alkylsulfone, 4-(5-methanesulfonyl-[1,2,3,4]tetrazol-1-yl)-phenol (MSTP), as a selective and highly reactive -SH blocking reagent compatible with biological applications.


Differential regulation of anterior pituitary corticotrope function is observed in vivo but not in vitro in two lines of ethanol-sensitive mice.
Anterior pituitary corticotrope function was analyzed in the long sleep (LS) and short sleep (SS) lines of mice selectively bred for differences in sensitivity to ethanol. In vivo challenge with acute ethanol or CRH administration or the stress of novel handling resulted in a more pronounced increase in serum corticosterone levels in LS mice compared with SS mice. Likewise, in vivo administration of ethanol resulted in 3-fold higher levels of anterior pituitary pro-ACTH/endorphin mRNA in LS mice compared with SS mice. However, this differential regulation of the HPA axis during in vivo analysis was not observed during in vitro studies of anterior pituitary corticotrope function. Primary cultures of LS and SS anterior pituicytes responded appropriately but equivalently to a variety of secretagogues known to stimulate anterior pituitary ACTH secretion. These secretagogues included CRH (10 nM), dibutyryl-cAMP (1 mM), vasopressin (100 nM), and phorbol 12-myristate 13-acetate (10 nM). Ethanol had no direct stimulatory effect on pituitary ACTH secretion. Quantitation of anterior pituitary corticotrope peptide biosynthesis was determined by immunoprecipitation and sodium dodecyl sulfate-polyacrylamide gel electrophoresis of extracts from [35S]methionine-labeled anterior pituitary explants and from [35S]methionine-labeled primary cultures of anterior pituitary cells. LS mice pro-ACTH/endorphin biosynthesis in pituitary explants was 2-fold greater than pro-ACTH/endorphin biosynthesis in SS mice pituitary explants. However, in culture, isolated from hypothalamic and adrenal factors, the LS anterior pituitary pro-ACTH/endorphin biosynthetic rate became equivalent to the SS anterior pituitary pro-ACTH/endorphin biosynthetic rate.(ABSTRACT TRUNCATED AT 250 WORDS)


Expression and distribution of id helix-loop-helix proteins in human astrocytic tumors.
The Id family of helix-loop-helix proteins is involved in a variety of processes, such as development, proliferation, and angiogenesis. In this study, we investigated the expression pattern of Id1, Id2, and Id3 in surgical specimens of human glial tumors. Western blot analysis demonstrated that all three Id proteins were expressed in astrocytic tumors. Expression levels in high-grade tumors were higher than in low-grade tumors. Immunohistochemical analysis confirmed that many of the tumor astrocytes exhibited strong Id1-3 IR. In contrast, in adult human normal brain, Id expression was low both in resting astrocytes and in endothelial cells. In tumor cells, Id proteins displayed cytoplasmic as well as nuclear localization. Id1-3 IR scores in tumor cells were positively correlated with proliferation indices. Moreover, Id1-3 IR was detected in endothelial cells of the astrocytic tumor blood vessels. The vascular Id1-3 expression correlated positively with tumor vascularity and grade. These results support the role of the Id gene family in the enhanced proliferative potential of tumor astrocytes. The evidence also supports the involvement of the Id gene family in tumor angiogenesis, a process that critically influences the malignant behavior of glial tumors.


Predictive value of functional status for mortality in patients on maintenance hemodialysis.
In patients receiving maintenance hemodialysis, laboratory indices (such as serum albumin concentration) are predominantly utilized to assess well-being, while measures of functional status are rarely applied. However, the serum albumin concentration declines with advancing age, and the mean age of patients starting maintenance hemodialysis is now over 63 years. Using a 14-level modified Karnofsky activity scale, we measured baseline functional status in 522 randomly selected hemodialysis patients and prospectively monitored them for 3 years to determine the predictive value of our modified Karnofsky score for mortality. At onset of study, serum albumin and creatinine concentrations as well as hematocrit were measured and the comorbid conditions documented. At baseline, the 522 subjects (270 women and 252 men) included 327 blacks (63%), 154 whites (29%), 31 Hispanics (6%), and 10 Asians (2%) of mean age 59 +/- (SD) 15 years. The mean duration of end-stage renal disease was 4 +/- 3.6 years, and the mean serum albumin concentration was 3.7 +/- 0.4 g/dl. 166 (32%) of the patients died during the observation period. Cox regression analysis revealed inverse relations between mortality and both our modified Karnofsky score (p = 0.0001) and serum albumin concentration (p = 0.001). The predictive value of a low modified Karnofsky score for mortality persisted after analysis of subjects stratified according to serum albumin concentration (< 4 g/dl, n = 382, p = 0.0001 vs. > or = 4 g/dl, n = 140, p = 0.008). With a modified Karnofsky score (< 70 vs. > or = 70), the relative risk of death during the 3-year follow-up period was 1.44 (95% confidence interval 1.236, 1.675; p < 0.0001). Forward stepwise Cox regression analysis showed that advanced age (p = 0.0005), white race (p = 0.0009), diabetes mellitus (p = 0.01), and a low serum albumin concentration (p = 0.003) were independently associated with an increased risk of mortality during follow-up after adjustment for other factors. A modified Karnofsky score (p = 0.14) did not predict survival in the Cox model when other independent variables were included. We conclude that in patients with end-stage renal disease sustained on maintenance hemodialysis, a poor functional status (measured on a modified Karnofsky activity scale) is associated with early mortality. Periodic measurement of modified Karnofsky score is a simple, low-cost, and reliable means of identifying patients on dialysis at risk for early death.


A 47 Years Lady with Intrathoracic Lipoma.
A case of a 47 years old female who presented to Mymensingh Medical College Hospital, Medicine Unit-5, complaining of severe dyspnea and occasional leg swelling. Chest X-ray, USG of chest and chest CT scan revealed a right sided giant intrathoracic mass extending across the posterior mediastinum into the left chest cavity. CT guided FNAC of right lung revealed lipoma.


Synthesis of two fluorescent GTPγS molecules and their biological relevance.
Fluorescent GTP analogues are utilized for an assortment of nucleic acid and protein characterization studies. Non-hydrolysable analogues such as GTPγS offer the advantage of keeping proteins in a GTP-bound conformation due to their resistance to hydrolysis into GDP. Two novel fluorescent GTPγS molecules were developed by linking fluorescein and tetramethylrhodamine to the γ-thiophosphate of GTPγS. Chemical and biological analysis of these two compounds revealed their successful synthesis and ability to bind to the nucleotide-binding site of tubulin. These two new fluorescent non-hydrolysable nucleotides offer new possibilities for biophysical and biochemical characterization of GTP-binding proteins.


[Various institutes and the private Tokyo Medical School and Nihon Medical School, following the closing of Saiseigakusha].
The private Saiseigakusha medical school was suddenly ordered closed on August 30, 1903, under pressure from the Ministry of Education and the Tokyo University Akamon faction (Meiiji Ikai). The more than 700 remaining medical students at Saiseigakusha were astonished and despondent to see the road to learning closed to them. However, Shigenori Sonoda, leader of the medical students, and four others sent out a manifesto to the more than 700 former Saiseigakusha students, calling them to assemble at the Hongo Central Hall. There they formed the Doso Igaku Koshukai ("Classmates' Medical Institute"), and resolved to continue their studies. Former Saiseigakusha lecturer Kiyotada Ishikawa and three others helped with this institute ("Tokyo Medical school"), and moved to 59 Sendagi-machi, Hongo. In April of 1910, the Tokyo Igakkou merged with the private Nippon Igakkou ("Japan Medical School"), to become the present Nippon Ika Daigaku ("Nippon Medical College").


Clinical applications of molecular imaging in sarcoma evaluation.
A wide range of molecular imaging techniques are available that can provide complementary information to conventional, anatomical imaging for the evaluation of known or suspected bone and soft tissue sarcomas. In particular, positron emission tomography (PET), particularly in the form of hybrid PET/CT technology, offers many potential advantages over current imaging approaches by delineating not only the extent of disease but also the biological heterogeneity that can exist both between and within sarcomas. This review discusses the clinical situations where nuclear medicine techniques can aid in the management of patients with sarcoma. These include biopsy guidance, whole body staging, therapeutic response assessment and evaluation of residual mass lesions after treatment.


Differential regulation of SK and BK channels by Ca(2+) signals from Ca(2+) channels and ryanodine receptors in guinea-pig urinary bladder myocytes.
Small-conductance (SK) and large-conductance (BK) Ca(2+)-activated K(+) channels are key regulators of excitability in urinary bladder smooth muscle (UBSM) of guinea-pig. The overall goal of this study was to define how SK and BK channels respond to Ca(2+) signals from voltage-dependent Ca(2+) channels (VDCCs) in the surface membrane and from ryanodine-sensitive Ca(2+) release channels or ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR) membrane. To characterize the role of SK channels in UBSM, the effects of the SK channel blocker apamin on phasic contractions were examined. Apamin caused a dose-dependent increase in the amplitude of phasic contractions over a broad concentration range (10(-10) to 10(-6) M). To determine the effects of Ca(2+) signals from VDCCs and RyRs to SK and BK channels, whole cell membrane current was measured in isolated myocytes bathed in physiological solutions. Depolarization (-70 to +10 mV for 100 ms) of isolated myocytes caused an inward Ca(2+) current (I(Ca)), followed by an outward current. The outward current was reduced in a dose-dependent manner by apamin (10(-10) to 10(-6) M), and designated I(SK). I(SK) had a mean amplitude of 53.8 +/- 6.1 pA or approximately 1.4 pA pF(-1) at +10 mV. The amplitude of I(SK) correlated with the peak I(Ca). Blocking I(Ca) abolished I(SK). In contrast, I(SK) was insensitive to the RyR blocker ryanodine (10 microM). These data indicate that Ca(2+) signals from VDCCs, but not from RyRs, activate SK channels. BK channel currents (I(BK)) were isolated from other currents by using the BK channel blockers tetraethylammonium ions (TEA(+); 1 mM) or iberiotoxin (200 nM). Voltage steps evoked transient and steady-state I(BK) components. Transient BK currents have previously been shown to result from BK channel activation by local Ca(2+) release through RyRs ('Ca(2+) sparks'). Transient BK currents were inhibited by ryanodine (10 microM), as expected, and had a mean amplitude of 152.6 pA at +10 mV. The mean number of transient BK currents during a voltage step (range 0 to 3) correlated with I(Ca). There was a long delay (52.4 +/- 2.7 ms) between activation of I(Ca) and the first transient BK current. In contrast, ryanodine did not affect the steady-state BK current (mean amplitude 135.4 pA) during the voltage step. The steady-state BK current was reduced 95 % by inhibition of VDCCs, suggesting that this process depends largely on Ca(2+) entry through VDCCs and not Ca(2+) release through RyRs. These results indicate that Ca(2+) entry through VDCCs activates both BK and SK channels, but Ca(2+) release (Ca(2+) sparks) through RyRs activates only BK channels.


Treatment of mcf-7 breast cancer cells with a red grape wine polyphenol fraction results in disruption of calcium homeostasis and cell cycle arrest causing selective cytotoxicity.
Food components influence the physiology by modulating gene expression and biochemical pathways within the human body. The disease-preventive roles of several fruit and vegetable components have been related to such properties. Polyphenolic components such as flavonoids are strong antioxidants and induce the expression of several xenobiotic-detoxifying enzymes. The mechanism of selective cytotoxicity induced by red grape wine polyphenols against MCF-7 breast cancer cells was investigated in relation to their interference with calcium homeostasis. MCF-7 cells showed an increase in cytosolic calcium levels within 10 min of treatment with the polyphenols. Immunohistochemical localization of calmodulin with secondary gold-labeled antibodies showed similar levels of gold labeling in both MCF-7 cells and the spontaneously immortalized, normal MCF-10A cell line. MCF-7 cells treated with the red wine polyphenol fraction (RWPF) showed swelling of endoplasmic reticulum, dissolution of the nucleus, and loss of plasma membrane integrity as well as reduced mitochondrial membrane potential. These cells were arrested at the G2/M interphase. By contrast, MCF-10A cells did not show such changes after RWPF treatment. The results suggest that polyphenol-induced calcium release may disrupt mitochondrial function and cause membrane damage, resulting in selective cytotoxicity toward MCF-7 cells. This property could further be developed toward breast cancer prevention strategies either independently or in conjunction with conventional prevention therapies where a positive drug-nutrient interaction can be demonstrated.


[Duodenum preserving resection of the head of the pancrease in therapy of pancreas divisum].
In 1-6% of the patients who are investigated by endoscopic retrograde cholangio-pancreatography a pancreas divisum can be found. In some patients pancreas divisum can lead to an acute relapsing and finally chronic pancreatitis (CP). Surgical intervention in these cases seems to offer a good chance of recovery. We report our experience with the duodenum-preserving resection of the head of the pancreas in 12 patients with pancreas divisum and CP. In all patients the preoperative evaluation showed clinical, functional or radiological signs of CP. The duodenum-preserving resection of the head of the pancreas was carried out in all patients without perioperative mortality. Ten postoperative versus eight preoperative patients showed a pathological exocrine function of the pancreas. Endocrine function, measured by the oral glucose tolerance test (OGTT), improved postoperatively in two patients. Eleven patients who were investigated after a mean follow-up time of 31 months (3-75 months) were completely pain free. No late mortality occurred. OGTT revealed a diabetic endocrine function in two patients. Disturbed exocrine pancreatic function had to be substituted in nine patients. One patient had to be reoperated by duct incision and renewal of the pancreatico-jejunostomy 10 months after the first operation. In conclusion, the duodenum-preserving resection of the head of the pancreas reduced pain in all patients with pancreas divisum and CP and may lead to an improvement of endocrine pancreatic function. Other, nonresecting procedures or endoscopic interventional therapy should be avoided in these patients.


The impact of advanced trauma life support course on graduates with a non-surgical medical background.
The aim of this study was to assess advanced trauma life support (ATLS) and combat trauma life support (CTLS) skills implementation among general practising physicians, its perceived utility in their routine daily practice as well as in their potential army combat assignments. One hundred and ten physicians, graduates of ATLS and CTLS courses, from the subspecialties of geriatrics, psychiatry and family medicine, were surveyed by telephone, to answer a specially designed questionnaire. The response rate was 82%. Professional distribution was: 6.6% geriatrics; 46.7% family physicians; and 46.7% psychaitrists. The number of trauma events treated by these physicians in their post-course practise was: geriatrics-three; family physicians-30; psychiatrists-18. We believe that a properly designed ATLS course, executed and applied to general practitioners, can be highly beneficial to trauma victims.


Finite element analysis of mechanics of lateral transmission of force in single muscle fiber.
Most of the myofibers in long muscles of vertebrates terminate within fascicles without reaching either end of the tendon, thus force generated in myofibers has to be transmitted laterally through the extracellular matrix (ECM) to adjacent fibers; which is defined as the lateral transmission of force in skeletal muscles. The goal of this study was to determine the mechanisms of lateral transmission of force between the myofiber and ECM. In this study, a 2D finite element model of single muscle fiber was developed to study the effects of mechanical properties of the endomysium and the tapered ends of myofiber on lateral transmission of force. Results showed that most of the force generated is transmitted near the end of the myofiber through shear to the endomysium, and the force transmitted to the end of the model increases with increased stiffness of ECM. This study also demonstrated that the tapered angle of the myofiber ends can reduce the stress concentration near the myofiber end while laterally transmitting force efficiently.


Retrobulbar Blood Flow Parameters in Patients With Anisometropic Amblyopia.
Introduction We aim to compare retrobulbar blood flow parameters between the amblyopic eye and the fellow eye in patients with anisometropic amblyopia. Methods Peak systolic velocity (PSV) and end-diastolic velocity (EDV) of the ophthalmic artery (OA), central retinal artery (CRA), and posterior ciliary artery (PCA) were measured by color Doppler imaging (CDI), and the resistivity index (RI) and pulsatility index (PI) were calculated in 62 patients aged 12-40 years with anisometropic amblyopia. Results The mean PSV values of OA, CRA, and PCA in amblyopic and fellow eyes were 30.38 ± 10.34, 8.45 ± 2.27, and 8.03 ± 2.77, and 33.73 ± 14.46, 8.35 ± 2.05, and 8.81 ± 2.77, respectively. The mean EDV values of OA, CRA, and PCA in amblyopic and fellow eyes were 6.86 ± 2.64, 1.47 ± 1.59, and 1.94 ± 2.03, and 8.57 ± 4.30, 1.80 ± 1.73, and 2.32 ± 1.20, respectively. The mean RI values of OA, CRA, and PCA in amblyopic and fellow eyes were 0.77 ± 0.10, 0.85 ± 0.14, and 0.78 ± 0.15, and 0.75 ± 0.07, 0.79 ± 0.20, and 0.74 ± 0.13, respectively. OA-PSV and OA-EDV values were significantly lower in the amblyopic eye than in the healthy eye (p < 0.05). OA-RI values were significantly higher (p < 0.05) in the amblyopic eye than in the healthy eye. Conclusions Considering the decrease in PSV and EDV and the increase in RI, which are the blood flow parameters of the amblyopic eye, our study may provide guidance to focus on increasing blood flow in the treatment of amblyopia.


Efficacy and safety of photodynamic therapy for non-muscle-invasive bladder cancer: a systematic review and meta-analysis.
Photodynamic therapy (PDT) is a promising treatment for non-muscle-invasive bladder cancer (NMIBC), we conducted this systematic review to comprehensively assess its efficacy and safety. A comprehensive literature research was conducted using PubMed, Web of Science, and Scopus, and studies reporting the safety and efficacy of PDT in NMIBC were included. Complete response (CR) rates, recurrence-free survival (RFS) at different time points, and complication incidences were extracted and synthesized. Pooled results were presented as rates with a 95% confidence interval (95% CI). Overall, 28 single arm studies were included in the meta-analysis. For unresectable NMIBC, therapeutic PDT achieved CR in 68% (95% CI: 59%-77%) of patients. Among these CR cases, 71% (95% CI: 56%-85%) and 38% (95% CI: 12%-64%) have a RFS longer than 12 and 24 months, respectively. For Tis patients, the CR rate was 68% (95% CI: 56%-80%), and 84% (95% CI: 48%-100%) and 13% (95% CI: 1%-32%) have a RFS longer than 12 and 24 months. For patients with resectable tumors, post-resection adjuvant PDT could provide a 12 and 24 months RFS in 81% (95% CI:76%-87%) and 56% (95% CI:41%-71%) of them. Especially, for NMIBC patients who failed BCG therapy, adjuvant PDT could still achieve a 1-year and 2-year RFS in 68% (95% CI:51%-86%) and 56% (95% CI:32%-81%) patients. The complications were mostly mild and transient, including lower urinary tract symptoms and photosensitivity. Both therapeutic and adjuvant PDT present satisfying safety and efficacy for NMIBC, including these cases that are resistant to the standard of care. As a promising option for NMIBC, PDT deserves further exploration by future high-quality research. https://inplasy.com/inplasy-2022-11-0043/, INPLASY2022110043.


In vitro effect of natural and semi-synthetic carbohydrate polymers on Chlamydia trachomatis infection.
The effect of different natural and semi-synthetic polysaccharides on Chlamydia trachomatis multiplication in Hela 229 cells was evaluated. Some neutral, negatively and positively charged carbohydrates were able, in a dose-dependent fashion, to inhibit chlamydial infection by interfering mainly with the adsorption process. The inhibiting compounds, whose effect was shown within the concentration range of 8-200 micrograms/ml, were in order of action: dextran sulphate > glyloid sulphate 4327 > glycogen sulphate 4427 > arabic gum = glyloid > chitosan > glycogen. Data obtained suggested that antichlamydial activity was not only related to the electric charge of these molecules but could also be attributed to other features of their polymeric backbone. Since carbohydrate polymers have also been shown to inhibit the early stages of infection by viral agents causing sexually transmitted diseases, the employment of these molecules for prevention or treatment of mixed viral-C. trachomatis infections can be hypothesized.


Peripheral-type benzodiazepine receptors in anxiety disorders.
Peripheral benzodiazepine receptors (pBDZr) were analyzed in lymphocyte membranes from patients with anxiety disorders (generalized anxiety disorder (GAD), n = 15; panic disorder (PD), n = 10; obsessive-compulsive disorder (OCD), n = 18), other mental disorders (n = 40) and 50 healthy controls, by the specific binding of 3H-PK11195. The number of binding sites (Bmax) was significantly decreased in groups with both GAD and OCD as compared with age-matched controls, by 45% and 25% respectively, whereas the binding affinity (Kd) was the same in all disorder and control groups. Conversely, no changes in binding capacity was observed in the other disorder groups and particularly in the one with PD. The abnormality in pBDZr observed in patients with GAD was restored to a normal value after long-term treatment with 2'-chloro-N-desmethyldiazepam, which also coincided with their recovery from anxiety. Our data suggest that the clinical heterogeneity in anxiety disorders might be related to different biological mechanisms and that lymphocyte pBDZr might be useful in demonstrating these differences.


Acute diabetes management: adult patients with hyperglycemic crises and hypoglycemia.
In acute diabetes conditions, management of the following 3 potential complications is required: diabetic ketoacidosis, hyperosmolar hyperglycemic state, and iatrogenic hypoglycemia. The hyperglycemic crises diabetic ketoacidosis and hyperosmolar hyperglycemic state are the 2 most serious metabolic complications of diabetes. Hypoglycemia, specifically iatrogenic hypoglycemia, results from treatments that raise circulating insulin levels and thus lower plasma glucose concentrations to an abnormally low level, which exposes the patient to potential harm. This article reviews the pathogenesis, precipitating or risk factors, diagnosis or identification, and treatment of these critical complications of diabetes. In addition, a case study on diabetic ketoacidosis is provided.


Inhibition of epidermal Langerhans cell function by low dose ultraviolet B radiation. Ultraviolet B radiation selectively modulates ICAM-1 (CD54) expression by murine Langerhans cells.
Immunosuppressive effects of low levels of ultraviolet B (UVB) radiation on cutaneous immune responses have been attributed to deleterious effects of UVB radiation on epidermal Langerhans cells (LC). To determine how UVB radiation modulates LC function we examined the effect of in vitro UVB exposure on LC accessory cell activity and surface phenotype. Exposure of BALB/c murine epidermal cells to low dose (less than or equal to 200 J/m2) UVB radiation in vitro inhibited their ability to support the mitogenic response of unstimulated, accessory cell-depleted splenic T cells to anti-CD3 mAb. LC accessory cell activity was also inhibited when LC were exposed to UVB radiation in situ, although several-fold higher doses of UVB radiation were required to achieve complete inhibition of LC function. This dose-dependent inhibition was mediated through a direct effect on LC that could not be reversed by IL-1 or IL-6 alone or in combination, or granulocyte-macrophage-CSF. TNF-alpha did not inhibit LC accessory cell function in this assay and anti-TNF-alpha neutralizing antibodies did not reverse the inhibitory effects of UVB radiation. UVB irradiated LC failed to participate in the anti-CD3-dependent clustering that normally occurs between T cells and LC during the proliferative response of murine T cells to anti-CD3 mAb, suggesting that UV radiation may interfere with accessory cell function by preventing intercellular adhesion. Two-color flow cytometric studies revealed low levels of the ICAM-1 on freshly isolated LC and some keratinocytes. ICAM-1 expression on LC increased 15 to 20-fold within the first 24 h in vitro and continued to increase during a 72-h culture period. The integrin LFA-1 was not identified on freshly isolated or cultured LC but was detected on responding T cells. Prior exposure of LC to UVB radiation (50 or 100 J/m2) inhibited the increase in ICAM-1 expression that normally occurs in vitro by up to 70% whereas surface levels of class II MHC Ag, CD45 and Fc-gamma receptors were not affected. Blocking studies revealed that anti-CD3 induced T cell proliferation and T cell-LC cluster formation was inhibited by both anti-LFA-1 and anti-ICAM-1 mAb suggesting that ICAM-1 expressed on LC must bind to LFA-1 on T cells to facilitate proliferative responses of T cells to anti-CD3 mAb. We conclude that the in vitro inhibitory effects of low dose UVB radiation on LC accessory function may result because UVB radiation prevents upregulation of ICAM-1 expression by LC in culture.(ABSTRACT TRUNCATED AT 250 WORDS)


MultipleXLab: A high-throughput portable live-imaging root phenotyping platform using deep learning and computer vision.
Profiling the plant root architecture is vital for selecting resilient crops that can efficiently take up water and nutrients. The high-performance imaging tools available to study root-growth dynamics with the optimal resolution are costly and stationary. In addition, performing nondestructive high-throughput phenotyping to extract the structural and morphological features of roots remains challenging. We developed the MultipleXLab: a modular, mobile, and cost-effective setup to tackle these limitations. The system can continuously monitor thousands of seeds from germination to root development based on a conventional camera attached to a motorized multiaxis-rotational stage and custom-built 3D-printed plate holder with integrated light-emitting diode lighting. We also developed an image segmentation model based on deep learning that allows the users to analyze the data automatically. We tested the MultipleXLab to monitor seed germination and root growth of Arabidopsis developmental, cell cycle, and auxin transport mutants non-invasively at high-throughput and showed that the system provides robust data and allows precise evaluation of germination index and hourly growth rate between mutants. MultipleXLab provides a flexible and user-friendly root phenotyping platform that is an attractive mobile alternative to high-end imaging platforms and stationary growth chambers. It can be used in numerous applications by plant biologists, the seed industry, crop scientists, and breeding companies.


Laparoscopic gastro-oesophageal antireflux surgery.
Recent improvement in the understanding of gastro-oesophageal antireflux mechanisms and the pathophysiology of the gastro-oesophageal reflux disease (GERD) has warranted the concept that antireflux surgery provides a valid, and sometimes superior, alternative to medical therapy in selected patients. The main indications for surgical treatment of symptomatic GERD are: failure of medical therapy to heal ulcerative oesophagitis or to prevent recurrence of stricture or other complications, and the development of aspiration pneumonia or other airway complications. The Belsey and Nissen fundoplication and the Hill posterior gastropexy are the three most widely used surgical procedures to control reflux. The success rate of these operations, performed openly, in relieving symptoms and healing the lesions is 80-90%. The laparoscopic approach provides an interesting alternative in antireflux surgery. It affords a potential to reduce some inherent complications of conventional surgery, provided the operator is technically experienced and well aware of the pathophysiological principles of this disease. It is also superbly convenient to the patient. The currently published short-term results of laparoscopic antireflux surgery are comparable to those of open surgery, but the technique is still young, and its final evaluation is not possible until long-term results are available.


Evolution to video-assisted thoracic surgery lobectomy after training: initial results of the first 30 patients.
In early-stage lung cancer, evidence is accumulating for the benefits of lobectomy by video-assisted thoracic surgery (VATS) over open lobectomy. Few thoracic training programs offer sufficient experience in this technically demanding procedure. This article describes the evolution of a new graduate's practice from open thoracotomy to VATS lobectomy. Our model involves a transition in technique from posterolateral thoracotomy to muscle-sparing thoracotomy and, ultimately, to VATS lobectomy. This approach was evaluated by examining outcomes of open thoracotomy patients before VATS lobectomy and outcomes of the initial 30 VATS patients. Data were collected prospectively. Before undertaking VATS lobectomy, 94 major pulmonary resections were performed by thoracotomy. Mortality was 1.2% for lobectomy and 0% for pneumonectomy. Use of the muscle-sparing thoracotomy increased from 17% of patients in the first half to 70% in the latter half of this group. For the first 30 VATS lobectomy patients, the mean operative time was 168 minutes. Median blood loss was 200 mL. Conversion rate to open thoracotomy was 13.3%. Mortality was 3.3% and morbidity was 26.7%. After short-term followup (mean followup 16 months), overall survival for stage I lung cancer was 96%. With our approach, new graduates of thoracic surgery programs can safely transition to VATS lobectomy. Gaining experience with the lateral muscle-sparing thoracotomy is an important step in the transition, as it offers similar operative exposure. Longterm disease-free and overall survival data are needed to evaluate our oncologic efficacy with this approach.


BEP-Like Correction of Nonequilibrium Thermodynamic Parameters of the Solvent-Assisted Reactions: The DFT and Ab Initio Study of Hydration, Peroxidation, and Enolization of Acetone and 1,1,1-Trifluoroacetone in Aqueous Solutions.
The mechanisms of enolization and reactions of nucleophilic addition to carbonyl compounds were analyzed by density functional theory (DFT) (PBE1PBE) and ab initio (DLPNO-CCSD(T)) level of theory using the interaction of water and hydrogen peroxide with acetone and 1,1,1-trifluoroacetone (TFA) as the reference reactions. The transition states of the studied reactions were localized within the integrated approach that includes both the dielectric continuum theory (polarizable continuum model (PCM)) and the cyclic or two-cluster explicit solvation models. The considered models provide proton transfer in the enolization, hydration, and peroxidation reactions by the Grotthuss mechanism. It is shown that the calculated activation parameters at a sufficiently high level of theory and a sufficiently flexible solvation model can be additionally refined using the Bell-Evans-Polanyi (BEP)-like correction (in a form of the Bell-Evans-Polanyi equation), which is linear scaling of the model potential energy surface according to the equilibrium parameters of the reference reaction (experiment or high-level calculation). Quite good correspondence of the corrected and reference activation parameters and the lower sensitivity of the calculation results to the choice of the solvation model indicate the high reliability of the proposed BEP-like correction technique.


Association of the Genetic Polymorphisms rs6259 and rs727428 of the SHBG Gene with Polycystic Ovary Syndrome Risk: A Meta-Analysis.
Background: Studies investigating the relationship between polymorphisms of the sex hormone-binding globulin (SHBG) gene and polycystic ovary syndrome (PCOS) have reported differing results. Therefore, the present meta-analysis was performed to clarify the effects of the SHBG rs6259 and rs727428 polymorphisms on PCOS risk. Materials and Methods: Published English language studies were selected through an extensive search of the Web of Science, PubMed, and EMBASE databases. Chinese studies were identified using Wan Fang, VIP, and the Chinese National Knowledge Infrastructure (CNKI) databases. The pooled odds ratio and 95% confidence interval were calculated using the random-effects model. Subgroup analyses and heterogeneity analyses were also performed. Results: A total of 1660 cases and 1312 controls were included in this meta-analysis. We found that the SHBG rs6259 polymorphism was not significantly associated with an increased risk of PCOS in any of the genetic models with significant heterogeneity; the results were consistent for all subgroups. A nonsignificant association between the rs727428 polymorphism and an increased risk of PCOS was also detected in all genetic models. Conclusions: The findings of this meta-analysis suggest that neither the SHBG rs6259 nor rs727428 polymorphism are associated with susceptibility to PCOS. However, because of the considerable heterogeneity and the small sample size, these pooled results should be interpreted with caution.


Controlling a model for bone marrow dynamics in cancer chemotherapy.
This paper analyzes a mathematical model for the growth of bone marrow cells under cell-cycle-specific cancer chemotherapy originally proposed by Fister and Panetta [8]. The model is formulated as an optimal control problem with control representing the drug dosage ( respectively its effect ) and objective of Bolza type depending on the control linearly, a so-called L(1)- objective. We apply the Maximum Principle, followed by high-order necessary conditions for optimality of singular arcs and give sufficient conditions for optimality based on the method of characteristics. Singular controls are eliminated as candidates for optimality, and easily verifiable conditions for strong local optimality of bang-bang controls are formulated in the form of transversality conditions at switching surfaces. Numerical simulations are given.


Exploring the key genes of fucoxanthin biosynthesis in Phaeodactylum tricornutum under phosphorus deficiency, red light and yellow light using WGCNA.
Weighted gene co-expression network analysis (WGCNA) is a method for analysing gene expression patterns across multiple samples, clustering genes with similar expression patterns and identifying key genes associated with specific traits or phenotypes. In this study, we investigated the effects of fucoxanthin accumulation in Phaeodactylum tricornutum in response to abiotic stresses of phosphorus deficiency, red light, and yellow light using transcriptome sequencing and weighted gene co-expression network analysis. The results showed that compared to the control, the fucoxanthin content of P. tricornutum was significantly increased after phosphorus deficiency and red light treatment (P<0.05), but significantly decreased after yellow light treatment (P<0.05). A weighted gene co-expression network was constructed using 10,392 genes obtained from transcriptome sequencing, and β=18 (R2>0.8) was chosen as a soft threshold in order to ensure a scale-free network. A total of 10 co-expression modules were identified by correlation analysis of fucoxanthin content, with the purple module positively correlated with fucoxanthin content (r=0.9, P=1E-200), and 9 key genes were identified, including five genes in the fucoxanthin biosynthesis pathway (DXR, PSY, PDS1, ZEP2, VDL2) and 4 transcription factors (bHLH5, HOX2, CCHH13, HSF1b). Further qRT-PCR confirmed that key genes were more highly expressed in the phosphorus deficiency treatment and linear regression analysis showed that the relative gene expressions were all highly correlated with the transcriptome data. The results of this study provide a basis for further investigation of the complex regulatory mechanisms of fucoxanthin in P. tricornutum.


Modulation of DNA methylation and gene expression in cultured sycamore cells treated by hypomethylating base analog.
The selective suppression of photosynthetic genes in both the nuclear and plastid genomes of the nonphotosynthetic white wild-type cell line of sycamore (Acer pseudoplatanus) has been found to be inversely related to the presence of a variety of methylated bases, especially 5-methylcytosine (5-MeCyt) and N6-methyladenine (N6-MeAde), localized in regions of the plastid genome containing silent genes. We used hypomethylating base analogs to manipulate the level of cytosine and adenine methylation in the white cells of sycamore, and examined the effects of changes in methylation on gene expression. Treatment with 5-azacytidine (5-AzaCyd) and N6-benzyladenine (N6-BzlAde) decreased cytosine and adenine methylation. This was accompanied by restoration of transcriptional activity in photosynthetic genes which are usually suppressed. Both 5-MeCyt and N6-MeAde suppressed nuclear gene expression, but only 5-MeCyt suppressed plastid gene expression.


Complementation between LLC-PK1 mutants affected in polypeptide hormone-receptor function.
The mutant LLC-PK1 cell lines FIB6 and FIB5/N4 were examined for responsiveness to the polypeptide hormones calcitonin and vasopressin. Both mutants exhibited little or no activation of adenylate cyclase or cAMP-dependent protein kinase (cAMP-PK) in response to calcitonin, but responded to vasopressin. Analysis of calcitonin receptor function demonstrated that both mutants bound less than 9 fmol 125I-labeled salmon calcitonin/mg cellular protein, which was about 1% of parental activity (642 fmol calcitonin bound/mg). Concomitant with reduced calcitonin binding, both mutants exhibited increased vasopressin binding (greater than 272 fmol [[3H]Arg]vasopressin bound/mg) compared to parental (166 fmol bound/mg). The concentration of vasopressin for half-maximal stimulation of adenylate cyclase in both mutants was comparable to that for LLC-PK1 cells (40 pM) and hence the increased binding activity was concluded to be due to increased numbers of functional vasopressin receptors in the mutants. Somatic cell hybrids formed between each mutant and LLC-PK1 cells exhibited normal hormone binding and activation of cAMP-PK in response to both vasopressin and calcitonin. The mutations affecting receptor function in FIB6 and FIB5/N4 were accordingly concluded to be recessive. Somatic cell hybrids between FIB6 and FIB5/N4 showed no complementation of the mutant phenotype, indicating that both cell lines were affected in the same gene. In contrast, somatic cell hybrids between FIB5/N4 and the 'receptorless' mutant M18 (which lacks functional calcitonin and vasopressin receptors) exhibited approximately the same responsiveness to vasopressin and to calcitonin as LLC-PK1. Complementation between two different mutations affecting polypeptide receptor function was thus observed. The results are discussed in terms of a proposed common pathway for processing of calcitonin and vasopressin receptors.


[Atrial stimulation and intranodal migration of sinus pacemaker in man (author's transl)].
In order to demonstrate, in man, sinus node pacemaker shift following atrial stimulation, we compared, in 26 patients, the curve of sinus node function obtained with Strauss' method with that resulting by the scanning with premature atrial stimulation of the first returning cycle following either a single premature atrial induced beat (140 ms shorter than the basic cycle) (group A), or a train of 8 consecutive atrial beats induced with a rate slightly faster (10 beats/m) than the control sinus rhythm (group B). Assuming that no changes in sinus pacemaker automaticity or in sinoatrial conduction occur owing to atrial stimulation, curves with the same shape should be observed if the site of the dominant pacemaker remains unchanged: whereas, different lengths of the compensatory phase (zone I) should be expected if an intranodal pacemaker shift occurs. For evaluating the length of the compensatory zone (zone I), we calculate, on the curve of the sinus node function, the mean value of the relation points included in the first third of the reset zone (zone II). According to our results, the length of the compensatory phase (zone I) evaluated on the curve resulting by the scanning of the first returning cycle following either a single premature atrial induced beat (group A), or eight consecutive atrial beats (group B) was shorter than that observed with the original Strauss' method (10% and 18% respectively). However, only in the group B, this difference was statistically significant. In addition, a significant inverse relationship between the shortening of the compensatory zone and the sinoatrial conduction index was also observed. Considering that our results have been corrected in such way as to repeal eventual changes in sinus pacemaker automaticity or sinoatrial conduction following atrial stimulation, the shortening of the compensatory zone, we have observed in our patients, strongly suggests an intranodal sinus pacemaker shift. If we assume that this result could represent an indirect evidence of this phenomenon, some clinical implications may follow: 1) another limitation, in addition to others known (intraatrial conduction delay, sinus arrhythmia, changes in sinus node automaticity, difference between retrograde and antegrade conduction time) could decrease the accuracy of atrial stimulation techniques in the estimation of the sinoatrial conduction time; 2) sinus pacemaker shift following atrial stimulation, may induce an understimulation of the true sinoatrial conduction time; however, according to our results, the error is generally small, so that it does no preclude the usefulness of atrial stimulation techniques in the evaluation of sinoatrial conduction; 3) the more evident and significant shortenings of the compensatory phase occurred with atrial pacing technique: this finding could explain why shorter sinoatrial conduction times are generally observed with Narula's method in comparison with Strauss' method.


Bone marrow lipofuscin.
Lipofuscins are commonly present in the macrophages of the marrow. In unstained preparations they may be confused with haemosiderin, but they are readily distinguished by fluorescence microscopy. In contrast to the belief that lipofuscins are a manifestation of senility, no age dependence has been demonstrated. Exceptionally large amounts have been found in illnesses accompanied by fever and leucocytosis, in keeping with the concept of their formation from insoluble remains of ingested cell fragments. It is probable that the ;sea-blue histiocytes', described in the literature, are macrophages laden with strikingly uniform granules of lipofuscin.


Context-dependent adaptation improves robustness of myoelectric control for upper-limb prostheses.
Dexterous upper-limb prostheses are available today to restore grasping, but an effective and reliable feed-forward control is still missing. The aim of this work was to improve the robustness and reliability of myoelectric control by using context information from sensors embedded within the prosthesis. We developed a context-driven myoelectric control scheme (cxMYO) that incorporates the inference of context information from proprioception (inertial measurement unit) and exteroception (force and grip aperture) sensors to modulate the outputs of myoelectric control. Further, a realistic evaluation of the cxMYO was performed online in able-bodied subjects using three functional tasks, during which the cxMYO was compared to a purely machine-learning-based myoelectric control (MYO). The results demonstrated that utilizing context information decreased the number of unwanted commands, improving the performance (success rate and dropped objects) in all three functional tasks. Specifically, the median number of objects dropped per round with cxMYO was zero in all three tasks and a significant increase in the number of successful transfers was seen in two out of three functional tasks. Additionally, the subjects reported better user experience. This is the first online evaluation of a method integrating information from multiple on-board prosthesis sensors to modulate the output of a machine-learning-based myoelectric controller. The proposed scheme is general and presents a simple, non-invasive and cost-effective approach for improving the robustness of myoelectric control.


[Research on the relation between ACE gene I/D polymorphisms and sensitivity to endurance training of Han nationality male].
In order to seek the marks of the genes, the relation between the influence of endurance training on aerobic ability and ACE Gene I/D Polymorphisms were studied. 102 army recruits of Han nationality from North China for an 18 week en durance training of 5000m distance. Their VO2(max), VT and the left ventricular structure and function were measured before and after the training. We also tested their ACE Gene I/D Polymorphisms with PCR-AFLP method. The compliance of VO2(max), VT and left ventricular structure and function had improved after the training; the deltaVO2(max) of ID and II type was obviously higher than that of DD type (P < 0.05); there was obviously diference of deltaVO2(VT) in different ACE genotype (P < 0.05), the deltaVO2(VT) of type II was obviously higher than that of DD type (P < 0.05). I allele has obviously hereditary advantage on the sensitivity to aerobic training in VO2(max) and VT, and type II has relation on the sensitivity to aerobic training in VT; there is no relation between I/D polymorphism and the sensitivity to aerobic training on the structure and function of left ventricle.


Variability in Small Hive Beetle (Coleoptera: Nitidulidae) Reproduction in Laboratory and Field Experiments.
Experiments were conducted to examine how several key factors affect population growth of the small hive beetle, Aethina tumida Murray (Coleoptera: Nitidulidae). Laboratory experiments were conducted to examine effects of food quantity and temperature on reproduction of cohorts of young A. tumida adults (1:1 sex ratio) housed in experimental arenas. Daily numbers and total mass of larvae exiting arenas were highly variable within treatment. Either one or two cohorts of larvae were observed exiting the arenas. Food quantity, either 10 g or 20 g, did not significantly affect the number of larvae exiting arenas at 32°C, but did at 28°C; arenas provided 20 g food produced significantly more larvae than arenas provided 10 g. Temperature did not affect the total mass of larvae provided 10 g food, but did affect larval mass provided 20 g; beetles kept at 28°C produced more larval mass than at 32°C. Field experiments were conducted to examine A. tumida reproductive success in full strength bee colonies. Beetles were introduced into hives as egg-infested frames and as adults, and some bee colonies were artificially weakened through removal of sealed brood. Efforts were unsuccessful; no larvae were observed exiting from, or during the inspection of, any hives. Possible reasons for these results are discussed. The variability observed in A. tumida reproduction even in controlled laboratory conditions and the difficulty in causing beetle infestations in field experiments involving full colonies suggest that accurately forecasting the A. tumida severity in such colonies will be difficult.