Hyperspectral imaging and spectral unmixing for improving whole-body fluorescence cryo-imaging.
Whole-animal fluorescence cryo-imaging is an established technique that enables visualization of the biodistribution of labeled drugs, contrast agents, functional reporters and cells in detail. However, many tissues produce endogenous autofluorescence, which can confound interpretation of the cryo-imaging volumes. We describe a multi-channel, hyperspectral cryo-imaging system that acquires densely-sampled spectra at each pixel in the 3-dimensional stack. This information enables the use of spectral unmixing to isolate the fluorophore-of-interest from autofluorescence and/or other fluorescent reporters. In phantoms and a glioma xenograft model, we show that the approach improves detection limits, increases tumor contrast, and can dramatically alter image interpretation.


Economic grand rounds: did Medicare Part D improve access to medications?
This study examined medication use among Medicare beneficiaries and dually eligible beneficiaries before and after the implementation of Medicare Part D on January 1, 2006. Nationally representative 2004-2006 data from the Medical Expenditure Panel Survey were used. Two large classes of psychotropic medications (antidepressant and antipsychotic medications) and two large classes of nonpsychotropic medications (lipid-lowering and antihypertensive agents) were examined to determine whether changes in prescription patterns occurred as a result of the implementation of Part D. There was no strong evidence that Part D was associated with large changes in access to medications in the four classes of medications examined here.


Use of Bacillus amyloliquefaciens HZ-12 for High-Level Production of the Blood Glucose Lowering Compound, 1-Deoxynojirimycin (DNJ), and Nutraceutical Enriched Soybeans via Fermentation.
1-Deoxynojirimycin (DNJ) is an efficient α-glucosidase inhibitor (α-GI) with potential applications in the prevention and treatment of diabetes. In this study, 16 Bacillus strains were screened for α-GI rate, and the strain HZ-12 with the highest α-GI rate was identified as Bacillus amyloliquefaciens through the analysis of physiological biochemical characteristics and 16S rDNA sequence. By LC-MS/Q-TOF analysis, the α-GI component produced by B. amyloliquefaciens HZ-12 was identified as DNJ. Soybean was used as the substrate for the solid-state fermentation; 870 mg/kg DNJ was produced by B. amyloliquefaciens HZ-12 after optimizing the fermentation conditions and media, which was 3.83-fold higher than the initial yield. Also, evaluations of nutraceutical enrichment in the form of anticoagulant activity, antioxidant activity, total nitrogen (TN), and total reducing sugars (TRS) of the B. amyloliquefaciens HZ-12 fermented soybeans were substantially higher than unfermented soybeans. This study provided a promising strain for high-level production of DNJ and produced nutraceutical enriched soybeans by fermentation.


Electroconvulsive therapy in Norway: rates of use, clinical characteristics, diagnoses, and attitude.
The aim of the study was to describe the rate of use and demographic distribution of electroconvulsive therapy (ECT) in Norway in 2004, as well as the attitudes among Norwegian psychiatrists about ECT. A 42-item questionnaire on the practice of ECT was sent to 125 Norwegian psychiatric hospitals, district psychiatric centers, and child and adolescent psychiatric units in 2004. A total of 67 (54%) psychiatric units responded, including 26 (67%) of 39 psychiatric hospitals, 32 (46%) of 69 district psychiatric centers, and 9 (53%) of 17 child and adolescent units. There were 672 patients who received ECT during 2004, which gives a yearly incidence of 2.4 of 10,000 inhabitants. A total of 5.3% of all inpatients received ECT.The rate of ECT use varied from 1.83 to 3.44 per 10,000 inhabitants per year between the different health regions.Of the 672 patients, 394 reported their sex (59%), of which 135 were men and 259 were women (male-female ratio, 1:2). The most common diagnosis treated with ECT was depression, followed by bipolar disorder and schizoaffective disorder.The responders expressed generally positive attitudes toward ECT. Almost all considered ECT important, that hospitals should offer ECT, and that there are solid indications for such treatment. Most of the responders expressed concern about the underuse of ECT. Electroconvulsive therapy is widely available in Norway but its use is unevenly distributed between health regions. The attitudes toward ECT are generally positive among psychiatrists.


[Surgical treatment of lesions of the cruciate and collateral ligaments of the knee].
The paper describes a number of patients operated for recent lesions of cruciate anterior ligament associated with lesions of internal collateral ligament. Patients were controlled after a time from operation of a 4 months- 4 years. For an exact functional valuation, a personal protocol was used, elaborated from the methods of the Orthopedic School of Lion. In the majority of cases, the trauma was secondry to sport practice, expecially sky. The technique used were the O'Donoghue one for cruciate ligament and the Vigliani one for collateral. Results were in all cases very good.


Health status of clients receiving methadone maintenance treatment using the SF-36 health survey questionnaire.
This study investigated the health status of a representative sample of clients (35 Maori, 72 non-Maori) receiving methadone maintenance treatment in New Zealand, using the SF-36 health survey. The publication of New Zealand norms in 1999 enabled comparisons of the health of the Methadone Treatment Programme study participants with that of the New Zealand population. Although over 50% of participants rated their health as good, very good or excellent, 44% rated their health as fair or poor and compared with population norms, the health of the study participants was significantly poorer on all eight SF-36 scales. Male and female participants rated their health similarly to male and female clients attending another New Zealand Methadone Treatment Programme. Results highlighted the impact of a chronic disorder and co-existing health-related problems on the health and well-being and day-to-day functioning of this client group. Higher frequency of benzodiazepine use was associated with poorer social functioning, mental health and role functioning and higher frequency of cannabis use was associated with poorer role functioning due to emotional problems. Findings support routine monitoring of health status with clients receiving methadone maintenance treatment as a guide to preventative and treatment interventions and health maintenance strategies.


Generalized anxiety disorder.
Generalized anxiety disorder is a relatively new clinical entity and current understanding of this syndrome lacks a solid research base. However, useful generalizations can be derived from earlier studies of anxiety neurosis and other previously defined anxiety syndromes. Most persons with GAD are seen by primary care physicians, but recognizing these patients may be difficult. In the primary care setting they often present with physical complaints suggesting a specific organ system disease. Depression and substance abuse may be presenting problems in patients with primary GAD. Primary care physicians are usually able to provide appropriate care for generalized anxiety disorder patients. By keeping in mind the cognitive, behavioral, affective, and physiologic aspects of the syndrome, they can appropriately address the specific therapeutic needs of individual patients. The nature of the doctor-patient relationship in primary care favors the development of therapeutic trust that is important for effective management of GAD. Drug therapy is a useful adjunct in the treatment of many patients with GAD. However, the use of drugs as the sole therapeutic modality is seldom appropriate.


Gas bubble disease in farmed fish in Saudi Arabia.
Four outbreaks of gas bubble disease were encountered among farmed fish in Saudi Arabia. Two of them occurred among subadult (52.5 g) saltwater tilapia (Oreochromis spilurus), the first affecting about 50 per cent of the stock and resulting in about 30 per cent mortality, and the second affecting about 25 per cent of the population with about 5 per cent mortality. Another outbreak occurred among adult (270 g) brackish water (0.5 per cent salinity) tilapia (Oreochromis niloticus), affecting about 40 per cent of the population with about 25 per cent mortality. The fourth outbreak occurred among three-month-old (15 g) grouper (Epinephelus fuscogutiatus) and resulted in 10 per cent mortality. In all cases the total water gas pressure ranged between 111.2 and 113.4 per cent saturation and nitrogen was supersaturated while oxygen was undersaturated. The outbreaks were alleviated by reducing the gas pressure by splashing the source water or by switching to a source of water with lower gas pressure. However, in O niloticus the conditions of gas supersaturation resulted in a heavy infection by monogenetic trematodes which was treated with formalin at 40 mg/litre for seven hours on five successive days.


PI 3-kinases: hidden potentials revealed.
The potential oncogenicity of PI 3-kinases is revealed by two principal mechanisms: mutations causing gain of function and overexpression of wild-type proteins. Cancer-specific mutations in PIK3CA, the gene coding for the catalytic subunit p110alpha of PI 3-kinase, are oncogenic in the animal. These mutations are therefore significant determinants of the oncogenic cellular phenotype in human tumors and are appropriate and promising targets for small molecule inhibitors. Overexpression of wild-type p110beta, gamma and delta induces oncogenic transformation in cell culture. Although these non-alpha isoforms of PI 3-kinase have not been found mutated in human cancer, deregulated expression could contribute to cellular oncogenic properties and deserves increased attention.


GroEL can unfold late intermediates populated on the folding pathways of monellin.
The modulation of the folding mechanism of the small protein single-chain monellin (MNEI) by the Escherichia coli chaperone GroEL has been studied. In the absence of the chaperone, the folding of monellin occurs via three parallel routes. When folding is initiated in the presence of a saturating concentration of GroEL, only 50-60% of monellin molecules fold completely. The remaining 40-50% of the monellin molecules remain bound to the GroEL and are released only upon addition of ATP. It is shown that the basic folding mechanism of monellin is not altered by the presence of GroEL, but that it occurs via only one of the three available routes when folding is initiated in the presence of saturating concentrations of GroEL. Two pathways become nonoperational because GroEL binds very tightly to early intermediates that populate these pathways in a manner that makes the GroEL-bound intermediates incompetent to fold. This accounts for the monellin molecules that remain GroEL-bound at the end of the folding reaction. The third pathway remains operational because the GroEL-bound early intermediate on this pathway is folding-competent, suggesting that this early intermediate binds to GroEL in a manner that is different from that of the binding of the early intermediates on the other two pathways. It appears, therefore, that the same protein can bind GroEL in more than one way. The modulation of the folding energy landscape of monellin by GroEL occurs because GroEL binds folding intermediates on parallel folding pathways, in different ways, and with different affinities. Moreover, when GroEL is added to refolding monellin at different times after commencement of refolding, the unfolding of two late kinetic intermediates on two of the three folding pathways can be observed. It appears that the unfolding of late folding intermediates is enabled by a thermodynamic coupling mechanism, wherein GroEL binds more tightly to an early intermediate than to a late intermediate on a folding pathway, with preferential binding energy being larger than the stability of the late intermediate. Hence, it is shown that GroEL can inadvertently and passively cause, through its ability to bind different folding intermediates differentially, the unfolding of late productive intermediates on folding pathways, and that its unfolding action is not restricted solely to misfolded or kinetically trapped intermediates.


An atlas of human proximal epididymis reveals cell-specific functions and distinct roles for CFTR.
Spermatozoa released from the testis are unable to fertilize an egg without a coordinated process of maturation in the lumen of the epididymis. Relatively little is known about the molecular events that integrate this critical progression along the male genital ducts in man. Here, we use single cell RNA-sequencing to construct an atlas of the human proximal epididymis. We find that the CFTR, which is pivotal in normal epididymis fluid transport, is most abundant in surface epithelial cells in the efferent ducts and in rare clear cells in the caput epididymis, suggesting region-specific functional properties. We reveal transcriptional signatures for multiple cell clusters, which identify the individual roles of principal, apical, narrow, basal, clear, halo, and stromal cells in the epididymis. A marked cell type-specific distribution of function is seen along the duct with local specialization of individual cell types integrating processes of sperm maturation.


Solution structures of two structural isoforms of CMrVIA chi/lambda-conotoxin.
alpha-Conotoxins possess a conserved four-cysteine framework and disulfide linkages (C(1)(-)(3), C(2)(-)(4)) that fold toward the globular conformation with absolute fidelity. Despite the presence of a similar conserved set of cysteine framework, chi/lambda-conotoxins adopt an alternate disulfide-pairing (C(1)(-)(4), C(2)(-)(3)) and its consequent ribbon conformation, exhibiting distinct biological activities from alpha-conotoxins. chi/lambda-Conotoxin CMrVIA (VCCGYKLCHOC-COOH) isolated from the venom of Conus marmoreus natively exists in the ribbon conformation and induces seizures in mice at a potency that is of three orders higher than the non-native globular form. We have chemically synthesized two isoforms of CMrVIA conotoxin in the ribbon and globular conformation and determined their structures by (1)H NMR spectroscopy. The ribbon (PDB ID 2B5P) and globular conformations (PBD ID 2B5Q) were calculated to have paired-wise backbone RMSDs of 0.48 +/- 0.1 and 0.58 +/- 0.1 A respectively. Unlike the native globular alpha-conotoxins, the globular canonical form of CMrVIA chi/lambda-conotoxin exhibited heterogeneity in its solution structure as noted by the presence of minor conformers and poorer RMSD of structure calculation. Paired-wise backbone comparison between the native ribbon and the non-native globular form of CMrVIA conotoxin revealed an RMSD of 4.73 A, emphasizing their distinct conformational differences. These structural data are essential for the understanding of the structure-function activity of chi/lambda-conotoxins, as well as unraveling the folding propensities of these short peptide toxins.


The Improvement Effect and Mechanism of Longitudinal Ultrasonic Vibration on the Injection Molding Quality of a Polymeric Micro-Needle Array.
A polymeric micro-needle array with high quality has been fabricated using a longitudinal ultrasonic-assisted micro-injection molding (LUμIM) method. To realize the practicability and stability in actual industrial processing, this paper is aimed at studying the improvement mechanism of ultrasonic vibration on the molding quality. The melt-filling process in the micro-needle array cavity is simulated, and the improvement effect of ultrasonic vibration is discussed. The enhancement effect of ultrasonic vibration on material properties of polypropylene and polymethylmethacrylate parts are experimentally investigated. The results show that in the manufacturing of the micro-needle array part using LUμIM, the mold-filling quality is improved by the enhanced melt filling capability and pressure compensation effect, which are caused by the increased corner viscosity gradient, reduced the filling time and melt viscosity under ultrasonic vibration. Material properties of both the semi-crystalline polymer and amorphous polymer could be enhanced by the transformation of micromorphology. It is proved that for a semi-crystalline polymer, this novel method could be employed as a material properties enhancement method, and an optimal excitation voltage of ultrasonic vibration is obtained to achieve the best material properties.


A Statistical Analysis on the Effect of Antioxidants on the Thermal-Oxidative Stability of Commercial Mass- and Emulsion-Polymerized ABS.
In the present work, statistical analysis (16 processing conditions and 2 virgin unmodified samples) is performed to study the influence of antioxidants (AOs) during acrylonitrile-butadiene-styrene terpolymer (ABS) melt-blending (220 °C) on the degradation of the polybutadiene (PB) rich phase, the oxidation onset temperature (OOT), the oxidation peak temperature (OP), and the yellowing index (YI). Predictive equations are constructed, with a focus on three commercial AOs (two primary: Irganox 1076 and 245; and one secondary: Irgafos 168) and two commercial ABS types (mass- and emulsion-polymerized). Fourier transform infrared spectroscopy (FTIR) results indicate that the nitrile absorption peak at 2237 cm-1 is recommended as reference peak to identify chemical changes in the PB content. The melt processing of unmodified ABSs promotes a reduction in OOT and OP, and promotes an increase in the YI. ABS obtained by mass polymerization shows a higher thermal-oxidative stability. The addition of a primary AO increases the thermal-oxidative stability, whereas the secondary AO only increases OP. The addition of the two primary AOs has a synergetic effect resulting in higher OOT and OP values. Statistical analysis shows that OP data are influenced by all three AO types, but 0.2 m% of Irganox 1076 displays high potential in an industrial context.


Platelet cytosolic calcium concentration in patients with liver cirrhosis. Relationship with hepatic and systemic hemodynamics.
Due to structural and functional similarities between platelets and vascular smooth muscle cells, platelet cytosolic calcium concentration ([Ca2+]i) has been suggested to be a useful tool to study regulatory mechanisms of peripheral vascular tone. The aim of the present study was to investigate platelet [Ca2+]i in patients with cirrhosis and whether this parameter is related with the systemic and splanchnic vasodilatation found in these patients. Seventeen patients with cirrhosis and eight age- and sex-matched controls were studied. Mean arterial pressure, cardiac output, femoral blood flow and basal and thrombin-stimulated platelet [Ca2+]i were measured. Cardiac output (thermal dilution), azygos blood flow, hepatic venous pressure gradient and hepatic blood flow were also measured in patients with cirrhosis. Patients with cirrhosis had severe portal hypertension and a significantly higher cardiac output and femoral blood flow and a significantly lower systemic and femoral vascular resistance than controls. Patients with cirrhosis had a lower basal platelet [Ca2+]i than normal subjects. However, there was no relationship between platelet [Ca2+]i and any of the hemodynamic parameters that evaluate systemic or splanchnic vasodilatation. This study shows that cirrhotic patients with portal hypertension have a significant reduction in platelet basal [Ca2+]i. The lack of correlation between platelet [Ca2+]i and hepatic and systemic hemodynamics does not support the use of platelet [Ca2+]i as a model to study mechanisms involved in the pathophysiology of the hyperdynamic circulation associated to portal hypertension.


Selective neuronal staining in tardigrades and onychophorans provides insights into the evolution of segmental ganglia in panarthropods.
Although molecular analyses have contributed to a better resolution of the animal tree of life, the phylogenetic position of tardigrades (water bears) is still controversial, as they have been united alternatively with nematodes, arthropods, onychophorans (velvet worms), or onychophorans plus arthropods. Depending on the hypothesis favoured, segmental ganglia in tardigrades and arthropods might either have evolved independently, or they might well be homologous, suggesting that they were either lost in onychophorans or are a synapomorphy of tardigrades and arthropods. To evaluate these alternatives, we analysed the organisation of the nervous system in three tardigrade species using antisera directed against tyrosinated and acetylated tubulin, the amine transmitter serotonin, and the invertebrate neuropeptides FMRFamide, allatostatin and perisulfakinin. In addition, we performed retrograde staining of nerves in the onychophoran Euperipatoides rowelli in order to compare the serial locations of motor neurons within the nervous system relative to the appendages they serve in arthropods, tardigrades and onychophorans. Contrary to a previous report from a Macrobiotus species, our immunocytochemical and electron microscopic data revealed contralateral fibres and bundles of neurites in each trunk ganglion of three tardigrade species, including Macrobiotus cf. harmsworthi, Paramacrobiotus richtersi and Hypsibius dujardini. Moreover, we identified additional, extra-ganglionic commissures in the interpedal regions bridging the paired longitudinal connectives. Within the ganglia we found serially repeated sets of serotonin- and RFamid-like immunoreactive neurons. Furthermore, our data show that the trunk ganglia of tardigrades, which include the somata of motor neurons, are shifted anteriorly with respect to each corresponding leg pair, whereas no such shift is evident in the arrangement of motor neurons in the onychophoran nerve cords. Taken together, these data reveal three major correspondences between the segmental ganglia of tardigrades and arthropods, including (i) contralateral projections and commissures in each ganglion, (ii) segmentally repeated sets of immunoreactive neurons, and (iii) an anteriorly shifted (parasegmental) position of ganglia. These correspondences support the homology of segmental ganglia in tardigrades and arthropods, suggesting that these structures were either lost in Onychophora or, alternatively, evolved in the tardigrade/arthropod lineage.


Myocardial remodelling and tissue characterisation by cardiovascular magnetic resonance (CMR) in endurance athletes.
There is still some controversy about the benignity of structural changes observed in athlete's heart, especially regarding the observation of increased biomarkers and the presence of myocardial fibrosis (MF). Our purpose was to evaluate by cardiovascular magnetic resonance (CMR) the presence of diffuse as well as focal MF in a series of high-performance veteran endurance athletes. Thirty-four veteran healthy male endurance athletes, still being in regular training, with more than 10 years of training underwent a CMR. A cardiopulmonary exercise test was also performed to assess their maximal physical performance. The control group consisted in 12 non-trained normal individuals. We found an increase in both, right and left ventricular (LV) volumes in the athlete's group when compared with controls. There was no increase in indexed LV myocardial mass despite of a significantly increased maximal myocardial wall thickness in comparison to controls. Native T1 values and extracellular volume (ECV) were normal in all cases. We did not find differences in native T1 values and ECV between both groups. In three athletes (9%), non-ischaemic late gadolinium enhancement (LGE) was observed. We did not find a correlation between total training volume and presence of LGE or with the ECV value. Our results show that the majority of veteran endurance athletes present with myocardial remodelling without MF as a physiological adaptive phenomenon. In the only three athletes with focal MF, the LGE pattern observed suggests an intercurrent event not related with the remodelling phenomenon.


Resection of olfactory groove meningioma - a review of complications and prognostic factors.
High complication rates have been cited following olfactory groove meningioma (OGM) resection but data are lacking on attendant risk factors. We aimed to review the complications following OGM resection and identify prognostic factors. A retrospective review was performed on 34 consecutive patients who underwent primary OGM resection at a single London institution between March 2008 and February 2013. Collected data included patient comorbidities, pre-operative corticosteroid use, tumour characteristics, imaging features, operative details, extent of resection, histology, use of elective post-operative ventilation, complications, recurrence and mortality. Complication rate was 39%. 58% of complications required intensive care or re-operation. Higher complication rates occurred with OGM > 40 mm diameter versus ≤ 40 mm (53 vs. 28%; p = 0.16); OGM with versus without severe perilesional oedema (59 vs. 19%; p = 0.26), more evident when corrected for tumour size; and patients receiving 1-2 days versus 3-5 days of pre-operative dexamethasone (75 vs. 19%; p = 0.016). Patients who were electively ventilated post-operatively versus those who were not had higher risk tumours but a lower complication rate (17 vs. 44%; p = 0.36) and a higher proportion making a good recovery (83 vs. 55%; p = 0.20). Complete versus incomplete resection had a higher complication rate (50 vs. 23%; p = 0.16) but no recurrence (0 vs. 25%; p = 0.07). Risk of morbidity with OGM resection is high. Higher complication risk is associated with larger tumours and greater perilesional oedema. Pre-operative dexamethasone for 3-5 days versus shorter periods may reduce the risk of complications. We describe a characteristic pattern of perilesional oedema termed 'sabre-tooth' sign, whose presence is associated with a higher complication rate and may represent an important radiological prognostic sign. Elective post-operative ventilation for patients with high-risk tumours may reduce the risk of complications.


Outdoor light at night (LAN) is correlated with eveningness in adolescents.
External zeitgebers synchronize the human circadian rhythm of sleep and wakefulness. Humans adapt their chronotype to the day-night cycle, the strongest external zeitgeber. The human circadian rhythm shifts to evening-type orientation when daylight is prolonged into the evening and night hours by artificial light sources. Data from a survey of 1507 German adolescents covering questions about chronotype and electronic screen media use combined with nocturnal satellite image data suggest a relationship between chronotype and artificial nocturnal light. Adolescents living in brightly illuminated urban districts had a stronger evening-type orientation than adolescents living in darker and more rural municipalities. This result persisted when controlling for time use of electronic screen media, intake of stimulants, type of school, age, puberty status, time of sunrise, sex, and population density. Time spent on electronic screen media use-a source of indoor light at night-is also correlated with eveningness, as well as intake of stimulants, age, and puberty status, and, to a lesser degree, type of school and time of sunrise. Adequate urban development design and parents limiting adolescents' electronic screen media use in the evening could help to adjust adolescents' zeitgeber to early school schedules when they provide appropriate lighting conditions for daytime and for nighttime.


Speech recognition and acoustic features in combined electric and acoustic stimulation.
In this study, the authors aimed to identify speech information processed by a hearing aid (HA) that is additive to information processed by a cochlear implant (CI) as a function of signal-to-noise ratio (SNR). Speech recognition was measured with CI alone, HA alone, and CI + HA. Ten participants were separated into 2 groups; good (aided pure-tone average [PTA] < 55 dB) and poor (aided PTA ≥ 55 dB) at audiometric frequencies ≤ 1 kHz in HA. Results showed that the good-aided PTA group derived a clear bimodal benefit (performance difference between CI + HA and CI alone) for vowel and sentence recognition in noise, whereas the poor-aided PTA group received little benefit across speech tests and SNRs. Results also showed that a better aided PTA helped in processing cues embedded in both low and high frequencies; none of these cues was significantly perceived by the poor-aided PTA group. The aided PTA is an important indicator for bimodal advantage in speech perception. The lack of bimodal benefits in the poor group may be attributed to the nonoptimal HA fitting. Bimodal listening provides a synergistic effect for cues in both low- and high-frequency components in speech.


Electrical conductivity of aqueous polyelectrolyte solutions in the presence of counterion condensation: the scaling approach revisited.
The conductometric properties of aqueous polyelectrolyte solutions in the absence of added salt are reviewed in the light of the dynamic scaling description of the polymer conformation in different concentration regimes, recently proposed by Dobrynin and Rubinstein [Macromolecules 28, 1859 (1995); 32, 915 (1999)]. The scaling approach to the transport properties of polyelectrolyte solutions allows us to separate contributions due to polymer conformation from those due to the ionic character of the chain, and offers the possibility to extend the validity of the Manning conductivity model to the dilute and semidilute regimes. Moreover, the quality of the solvent, influencing the polyion-counterion interactions, can be properly taken into account. The electrical conductivity predicted by this scaling approach compares reasonably well with the observed values for a model polyelectrolyte (polyacrylate sodium salt in aqueous solutions, good solvent condition) over an extended concentration range from the dilute to the semidilute regime.


Treatment to suppression of focal lesions on positron emission tomography-computed tomography is a therapeutic goal in newly diagnosed multiple myeloma.
Fluorine-18 fluorodeoxyglucose positron emission tomography with computed tomography attenuation correction (PET-CT) in myeloma can detect and enumerate focal lesions by the quantitative characterization of metabolic activity. The aim of this study was to determine the prognostic significance of the suppression of PET-CT activity at a number of time points post therapy initiation: day 7, post induction, post transplant, and at maintenance therapy. As part of the TT4-6 trial series, 596 patients underwent baseline PET-CT and were evaluated serially during their disease course using peak standardized uptake values above background red marrow signal. We demonstrate that the presence of more than 3 focal lesions at presentation identifies a group of patients with an adverse progression-free survival and overall survival. At day 7 of therapy, patients with complete focal lesion signal suppression revert to the same prognosis as those with no lesions at diagnosis. At later time points, the continued suppression of signal remains prognostically important. We conclude that for newly diagnosed patients with focal lesions, treatment until these lesions are suppressed is an important therapeutic goal as the prognosis of these patients is the same as those without lesions at diagnosis. (clinicaltrials.gov identifiers: 00734877, 02128230, 00869232, 00871013).


Expanding intestinal stem cells in culture.
Culturing intestinal stem cells into 3D organoids results in heterogeneous cell populations, reflecting the in vivo cell type diversity. In a recent paper published in Nature, Wang et al. established a culture condition for a highly homogeneous population of intestinal stem cells.


Comparative Assessment of Platinum Salts and Taxane Group Hypersensitivity Reactions, The Role of Skin Tests in Diagnosis?
We aimed to investigate the role of skin tests (ST) in the diagnosis of hypersensitivity reactions (HSRs) with platinum salts (PS) and taxane (TX) groups drugs and their reliability in patient management. Patients' data who developed immediate HSR with PS and TX were recorded and ST was performed. The gradual challenge was applied to all patients with ST negative and grade 1-2 with the suspect drug. In total, the data of 104 patients (74 with PS, 30 with TX) who developed HSR against PS and TX were shared. The gradual challenge was applied to 72 ST negative and grade 1-2 patients (46 PS group, 26 TX group). The gradual challenge was negative in 39 patients in the PS group and 23 patients in the Tx group. The negative predictive value (NPV) for PS was 83% and NPV for TX was 88%. We found significantly higher skin test positivity in patients with PS and TX and grade 3 HSR (p = 0.007, p = 0.001). A significant correlation was found between skin test positivity and early onset of symptoms (p = 0.001 for PS, p = 0.015 for TX). In terms of symptoms witnessed in HSR, we observed the itching, urticaria, hypotension, syncope, and abdominal pain symptoms significantly more in the group with a positive skin test (p < 0.024, p < 0.001, p < 0.001, p < 0.002, and p < 0.025, respectively). We found very high NPV values for PS and TX. We found that the gradual challenge applied to patients with negative skin tests is reliable if Grade 3 HSR is not observed and with this approach, unnecessary desensitization processes and/or drug alterations can be avoided.


The Five-Step Rhinoplasty Dead Space Closure Technique.
The creation of dead space in rhinoplasty creates a welcoming environment for erratic soft -tissue contraction. If rhinoplasty surgeons can control and reliably predict skin contraction and wound healing, rhinoplasty results will undoubtedly improve. Obliteration of dead space is a key component in rhinoplasty as it minimizes soft-tissue contraction, resulting in a more predictable outcome. In this article, the authors present a systematic five-step dead space closure surgical plan.


Effects of fructose 2,6-bisphosphate on phosphoglucomutase from plants.
Fructose 2,6-bisphosphate affects phosphoglucomutase from plant and animal sources in a similar way. As previously found with rabbit muscle phosphoglucomutase, fructose 2,6-bisphosphate cannot substitute for glucose 1,6-bisphosphate as a cofactor in the reaction catalyzed by phosphoglucomutase from potato tubers, pea seeds, and string-beans. In the presence of glucose 1,6-bisphosphate, fructose 2,6-bisphosphate inhibits phosphoglucomutase from potato tubers. Activation of phosphoglucomutase from plant sources by fructose 2,6-bisphosphate reported by others was probably due to contamination of the commercial preparation of fructose 2,6-bisphosphate by glucose 1,6-bisphosphate.


Characteristics of a Galactose-adapted Sugarcane Cell Line Grown in Suspension Culture.
Although d-galactose is normally toxic to sugarcane (Saccharum sp.) cells, a cell line that grows on 100 mm galactose has been propagated. Nonadapted cells in a medium containing galactose instead of sucrose accumulate UDP-galactose; these cells also have much lower UDP-galactose 4-epimerase (EC 188.8.131.52) activity than do adapted cells. This enzyme may determine whether or not galactose will cause toxicity symptoms to develop. The growth rate of galactose-adapted cells is similar to most cell lines on several other carbohydrates. The galactose-adapted cells are also similar to sucrose stock cells in cell wall composition and sugar phosphate concentrations, but, like the nonadapted cells, accumulate free galactose.


Relevance of Cortical and Hippocampal Interneuron Functional Diversity to General Anesthetic Mechanisms: A Narrative Review.
General anesthetics disrupt brain processes involved in consciousness by altering synaptic patterns of excitation and inhibition. In the cerebral cortex and hippocampus, GABAergic inhibition is largely mediated by inhibitory interneurons, a heterogeneous group of specialized neuronal subtypes that form characteristic microcircuits with excitatory neurons. Distinct interneuron subtypes regulate specific excitatory neuron networks during normal behavior, but how these interneuron subtypes are affected by general anesthetics is unclear. This narrative review summarizes current principles of the synaptic architecture of cortical and interneuron subtypes, their contributions to different forms of inhibition, and their roles in distinct neuronal microcircuits. The molecular and cellular targets in these circuits that are sensitive to anesthetics are reviewed in the context of how anesthetics impact interneuron function in a subtype-specific manner. The implications of this functional interneuron diversity for mechanisms of anesthesia are discussed, as are their implications for anesthetic-induced changes in neural plasticity and overall brain function.


Factorial structure of the perception of risk factors for type 2 diabetes scale: exploratory and confirmatory factor analyses.
The extent to which individuals' perceptions of risk for type 2 diabetes are related to their actual risks and health-promoting behaviours is not well known. Yet perception of risk for type 2 diabetes may influence the likelihood that individual would engage in preventive behaviours. The purpose of this study was to evaluate the psychometric properties of the perception of risk factors for type 2 diabetes (PRF-T2DM). A descriptive, correlational, methodological design was used to conduct this study. The sample consisted of 629 adults from 42 states of the United States. A demographic questionnaire, the PRF-T2DM, the health-promoting lifestyle profile II and the depressive cognition scale were used to collect the data. Data analyses consisted of descriptive statistics, scale and item analyses, Pearson's correlation analysis, and exploratory and confirmatory factor analyses. The PRF-T2DM has a Cronbach's alpha of 0.81. Both extracted factors had Cronbach's alphas of 0.74 and 0.80, respectively. Most inter-item and item-to-total correlation coefficients for factor 1 and factor 2 met the recommended criteria of r=0.30 to r=0.70. The PRF-T2DM achieved all minimum recommended criteria for model fit (χ(2) /d.f.=2.33, goodness of fit index=0.95, adjusted goodness of fit index=0.93, comparative fit index=0.94, root mean square error of approximation=0.05, root mean residual=0.05 and the P value for test of close fit=0.33). All statistical estimates and measures of model fit were above the standard recommended criteria. The scale has potential uses in research and clinical practice. Further development and psychometric evaluation of the PRF-T2DM is warranted.


Involvement of nitric oxide in IFN-gamma-mediated reduction of microvessel smooth muscle cell proliferation.
Previous studies in our laboratory demonstrated that murine cerebral microvessel smooth muscle cells (SMC) activate syngeneic CD4+ T-cells in vitro. These T-cells, or their culture supernatants, in turn, strongly inhibit proliferation of the SMC. The present study focuses on IFN-gamma as a mediator of inhibition of SMC proliferation, and addresses the molecular mechanism of this inhibition. IFN-gamma profoundly reduced the proliferation of murine brain microvessel smooth muscle cells in vitro. Three lines of evidence indicate that nitric oxide contributed to this effect: (1) IFN-gamma-mediated inhibition of proliferation correlated with the quantity of nitrite, a stable breakdown product of nitric oxide, in culture supernatants; (2) the addition of N(g)- monomethyl-l-arginine, and inhibitor of nitric oxide synthesis, restored proliferation to control or near control levels; and (3) the addition of hemoglobin, which has a high affinity for, and thus sequesters nitric oxide, also resulted in significant restoration of the proliferative response. However, the nitric oxide donating chemical sodium nitro-prusside, at concentrations up to 100 microM, had no direct cytostatic effect. These results suggest that nitric oxide is a necessary but insufficient component in IFN-gamma-mediated inhibition of microvessel smooth muscle cell proliferation. TNF-alpha also stimulated nitric oxide production by the smooth muscle cells, but was not as potent as IFN-gamma at inhibiting proliferation. Knowledge of the physiological effects of lymphokines on cells of the brain microvasculature will contribute towards a better understanding of inflammatory processes in diseases such as multiple sclerosis and infectious encephalitis.


Structural domains of the poliovirus polyprotein are major determinants for proteolytic cleavage at Gln-Gly pairs.
The processing of poliovirus precursor polypeptides provides a valuable system in which to study the recognition and interaction of a proteolytic enzyme with its substrates. Processing of the poliovirus polyprotein includes cleavage between 9 of 13 available glutamineglycine (Q-G) pairs by the activity of a virally encoded proteinase, 3C. In this study, we assess the importance of primary, secondary, and tertiary structural determinants in the cleavage at two Q-G pairs in the capsid protein precursor, P1. Employing site-directed mutagenesis of cDNA copies of poliovirus RNA, we have made specific alterations in regions of the P1 capsid precursor and have assayed the effect of these alterations on proteinase cleavage at the two Q-G pairs. We have also introduced additional Q-G pairs into P1 and demonstrated that the proteinase can recognize some of the inserted Q-G pairs as cleavage sites. By correlating the predicted three-dimensional structures and the processing phenotypes of several altered P1 precursors, we are able to rank the importance of determinants required for P1 processing. While a Q-G pair appears to be the primary determinant in proteinase recognition, the tertiary location of a Q-G pair in the precursor either allows or prevents processing at that pair. Our results also suggest that the proper folding of at least two of the three P1 beta-barrel structures is required for efficient proteinase cleavage at Q-G pairs.


[Bilateral solitary fungus balls sphenoid sinus].
Diagnosis of sphenoid sinus disease is very difficult because the location of sinus is deep and hidden within the skull and the symptoms of sphenoiditis are nonspecific. However, thanks to new technologies in imaging (CT and MRI) and nasal endoscopy, the literature on sphenoid sinus fungus ball have been published more. But all of the SSFB which have been reported are isolated or unilateral. We reported one rare case of bilateral sphenoid sinus fungus balls. This patient was treated in our department. Headache was the only symptom in this case. The patient was treated by sphenoidotomy via endoscopic approach and removal both of the lesions. No recurrence was found after 6-months follow-up.


Effect of eucalyptus growth regulators on the water loss from plant leaves.
Three closely related growth regulators (G) that are present in some myrtaceous plants were examined for possible anti-transpirant effects. The bioassay material involved cuttings of mung bean and Eucalyptus rupicola. Stomatal resistance was determined by a diffusion porometer. Water loss was equated with water uptake by the cutting over a 24-hour period.In both bioassays, G reduced water loss. The reduced water loss was associated with stomatal closure. This anti-transpirant effect of G was five to ten times less than that of abscisic acid. The stomatal resistance to the diffusion of water vapor from mung bean leaves increased within 1 hour of application of G. Marked stomatal closure occurred after 6 hours when 5 to 7 micrograms of G had accumulated in the leaves.These results and earlier evidence, suggest that G growth regulators are involved in the water economy of Eucalyptus and perhaps other related genera.


Lactating adenoma: a diagnosis of exclusion.
This is a case of a large lactating adenoma which developed in a 26 year old primagravida during the third trimester of her pregnancy. The presentation was that of a grossly enlarged and engorged breast with breast erythema, warmth and tenderness. Radiologic and pathologic examinations were difficult because of the lactational changes in the breast and areas of infarcted tissue within the large tumor. Skin biopsies and core biopsies of the mass were performed to exclude malignancy. Surgical resection of the mass was necessary for definitive diagnosis. The pathology proved to be a lactating adenoma, which is the most prevalent breast mass in young pregnant females. The large size of this tumor, and the presentation of breast erythema and edema raised the possibility of inflammatory breast cancer. Following surgical resection and definitive diagnosis of this tumor, the patient required plastic surgical reconstruction of the breast because of redundant breast tissue. Although most lactating adenomas spontaneously involute, the diagnosis is not always straight-forward and surgical resection may be required for definitive diagnosis and exclusion of other pathologic processes.


Sympathetic modulation of activity in Adelta- and C-primary nociceptive afferents after intradermal injection of capsaicin in rats.
Neuropathic and inflammatory pain can be modulated by the sympathetic nervous system. In some pain models, sympathetic postganglionic efferents are involved in the modulation of nociceptive transmission in the periphery. The purpose of this study is to examine the sensitization of Adelta- and C-primary afferent nociceptors induced by intradermal injection of capsaicin (CAP) to see whether the presence of sympathetic efferents is essential for the sensitization. Single primary afferent discharges were recorded from the tibial nerve after the fiber types were identified by conduction velocity in anesthetized rats. An enhanced response of some Adelta- and most C-primary afferent fibers to mechanical stimuli was seen in sham-sympathectomized rats after CAP (1%, 15 mul) injection, but the enhanced responses of both Adelta- and C-fibers were reduced after sympathetic postganglionic efferents were removed. Peripheral pretreatment with norepinephrine by intraarterial injection could restore and prolong the CAP-induced enhancement of responses under sympathectomized conditions. In sympathetically intact rats, pretreatment with an alpha(1)-adrenergic receptor antagonist (terazosin) blocked completely the enhanced responses of C-fibers after CAP injection in sympathetically intact rats without significantly affecting the enhanced responses of Adelta-fibers. In contrast, a blockade of alpha(2)-adrenergic receptors by yohimbine only slightly reduced the CAP-evoked enhancement of responses. We conclude that the presence of sympathetic efferents is essential for the CAP-induced sensitization of Adelta- and C-primary afferent fibers to mechanical stimuli and that alpha(1)-adrenergic receptors play a major role in the sympathetic modulation of C-nociceptor sensitivity in the periphery.


Characterization of the heme and pyridoxal phosphate cofactors of human cystathionine beta-synthase reveals nonequivalent active sites.
Cystathionine beta-synthase is an unusual enzyme that requires the cofactors heme and pyridoxal phosphate (PLP) to catalyze the condensation of homocysteine and serine to generate cystathionine. This transsulfuration reaction represents one of two major cellular routes for detoxification of homocysteine, which is a risk factor for atherosclerosis. While the beta-replacement reaction catalyzed by this enzyme suggests a role for the pyridoxal phosphate, the role of the heme is uncertain. In this study we have examined the effect of changing one of the ligands to the heme on the activity of the enzyme. Binding of carbon monooxide results in the displacement of a thiolate ligand to the ferrous heme, and is accompanied by complete loss of cystathionine beta-synthase activity. Furthermore, inhibition by CO is competitive with respect to homocysteine, providing the first indication that the homocysteine binding site is in the proximity of heme. Binding of both CO and cyanide to ferrous cystathionine beta-synthase occurs in two distinct isotherms and indicates that the hemes are nonequivalent. We have employed fluorescence spectroscopy to characterize the bound PLP and its interaction with serine. PLP bound to cystathionine beta-synthase is weakly fluorescent and exists as a mixture of the protonated and unprotonated tautomers. Reaction with hydroxylamine releases the oxime and greatly enhances the associated fluorescence. Binding of serine is accompanied by a shift to the unprotonated tautomer of the external aldimine as well as the appearance of a new fluorescent species at approximately 400 nm that could be due to the aminoacrylate or to a gemdiamine intermediate. These data provide the first characterization of the PLP bound to cystathionine beta-synthase. Treatment of cystathionine beta-synthase with hydroxylamine releases two PLPs after 1 day and results in complete loss of activity. Incubation for an additional 3-4 days results in the release of two more PLPs. These data lead us to revise the PLP stoichiometry to 4 per tetramer, and to the conclusion that the heme and PLP sites in cystathionine beta-synthase are nonequivalent.


Localisation of hyaluronan in the human intestinal wall.
By using biotin labelled proteoglycan core protein and an avidin enzyme system, hyaluronan (hyaluronic acid) was visualised in specimens of human jejunum. Intense staining for hyaluronan was seen in the loose connective tissue of the villi and of lamina propria while the epithelial layer was unstained. The muscularis mucosae showed only faint staining. The accumulation of hyaluronan in the subepithelial layer of the jejunal mucosa indicates that the previously reported high jejunal secretion of hyaluronan is due to passive diffusion from the subepithelial interstitium. The physicochemical characteristics conferred by hyaluronan may be important for the villi function.


Day-old chicken quality and performance of broiler chickens from 3 different hatching systems.
In on-farm hatching systems, eggs are transported at d 18 of incubation to the broiler farm, where chickens have immediate access to feed and water after hatching. In hatchery-fed systems, newly hatched chickens have immediate access to feed and water in the hatchery and are transported to the farm thereafter. Conventionally hatched chickens can remain without access to feed and water up to 72 h after hatching until placement on the farm. The current study compared day-old chicken quality, performance, and slaughter yield of broiler chickens that were on-farm hatched (OH), hatchery-fed (HF), or conventionally hatchery-hatched (HH). The experiment was performed in 6 rooms in 1 house. Each room contained 2 duplicate pens with approximately 1,155 chickens per pen; 2 rooms with each 2 duplicate pens were assigned to 1 treatment. The experiment was repeated during 3 consecutive production cycles. Chickens originated from young parent stock flocks. Results showed that HF and OH chickens were heavier and longer than HH chickens at day (D) 1. Relative weight of stomach and intestines were highest for OH chickens. The OH chickens had worse day-old chicken quality in terms of navel condition and red hocks than HH and HF chickens. Treatments did not differ in first wk and total mortality. From D0 until slaughter age, body weight was highest for OH, followed by HF and HH. Furthermore, carcass weight at slaughter age (D40) was highest for OH chickens, followed by HF and HH chickens. Breast fillets showed a higher incidence of white striping and wooden breast in HF and OH chickens compared with HH chickens. In conclusion, the current study showed that both OH and HF chickens of young parent flocks had better growth performance, which could explain the higher prevalence of breast myopathies, compared with HH. The worse day-old chicken quality for OH compared with HH and HF does not seem to affect first wk mortality and later life performance.


Highly Active and Selective Electroreduction of N2 by the Catalysis of Ga Single Atoms Stabilized on Amorphous TiO2 Nanofibers.
The electroreduction of N2 under ambient conditions has emerged as one of the most promising technologies in chemistry, since it is a greener way to make NH3 than the traditional Haber-Bosch process. However, it is greatly challenged with a low NH3 yield and faradaic efficiency (FE) because of the lack of highly active and selective catalysts. Inherently, transition (d-block) metals suffer from inferior selectivity due to fierce competition from H2 evolution, while post-transition (p-block) metals exhibit poor activity due to insufficient "π back-donation" behavior. Considering their distinct yet complementary electronic structures, here we propose a strategy to tackle the activity and selectivity challenge through the atomic dispersion of p-block metal on an all-amorphous transition-metal matrix. To address the activity issue, lotus-root-like amorphous TiO2 nanofibers are synthesized which, different from vacancy-engineered TiO2 nanocrystals reported previously, possess abundant intrinsic oxygen vacancies (VO) together with under-coordinated dangling bonds in nature, resulting in significantly enhanced N2 activation and electron transport capacity. To address the selectivity issue, well-isolated single atoms (SAs) of Ga are successfully synthesized through the confinement effect of VO, resulting in Ga-VO reactive sites with the maximum availability. It is revealed by density functional theory calculations that Ga SAs are favorable for the selective adsorption of N2 at the catalyst surface, while VO can facilitate N2 activation and reduction subsequently. Benefiting from this coupled activity/selectivity design, high NH3 yield (24.47 μg h-1 mg-1) and FE (48.64%) are achieved at an extremely low overpotential of -0.1 V vs RHE.


Clonidine and enphenamic acid interaction study in dogs.
The drug interaction between clonidine (Cl) and enphenamic acid (En.A.), a newer non-steroidal anti-inflammatory drug (NSAID) was studied in anaesthetized dogs. Prior administration of En.A. in animals modified the blood pressure response to clonidine. Thus En.A., administered 1 hr before clonidine, potentiated the hypertensive response and blocked the subsequent hypotensive response to clonidine. Intracerebroventricular administration of En.A. did not affect the usual blood pressure response to clonidine. Similarly, this interaction was not observed in reserpinized animals and it was only partially blocked in normal dogs, treated with tolazoline. It is concluded that En.A. interferes with blood pressure responses to clonidine and that this interaction is probably of a peripheral, vascular, nature.


Decision-tree analysis of control strategies.
A major focus of research on visually guided action is the identification of control strategies that map optical information to actions. The traditional approach has been to test the behavioral predictions of a few hypothesized strategies against subject behavior in environments in which various manipulations of available information have been made. While important and compelling results have been achieved with these methods, they are potentially limited by small sets of hypotheses and the methods used to test them. In this study, we introduce a novel application of data-mining techniques in an analysis of experimental data that is able to both describe and model human behavior. This method permits the rapid testing of a wide range of possible control strategies using arbitrarily complex combinations of optical variables. Through the use of decision-tree techniques, subject data can be transformed into an easily interpretable, algorithmic form. This output can then be immediately incorporated into a working model of subject behavior. We tested the effectiveness of this method in identifying the optical information used by human subjects in a collision-avoidance task. Our results comport with published research on collision-avoidance control strategies while also providing additional insight not possible with traditional methods. Further, the modeling component of our method produces behavior that closely resembles that of the subjects upon whose data the models were based. Taken together, the findings demonstrate that data-mining techniques provide powerful new tools for analyzing human data and building models that can be applied to a wide range of perception-action tasks, even outside the visual-control setting we describe.


[Factorial validity of the Spanish adaptation of the Maslach Burnout Inventory-General Survey].
To explore the factorial structure of a Spanish version of the "Maslach Burnout Inventory-General Survey" (MBI-GS). A cross-sectional study was conducted in 1999 among 149 municipal policemen in Tenerife, Spain. A questionnaire was applied to collect data on Professional Efficacy, Cynicism, and Burnout. Data were analyzed using factorial analysis and principal components with Varimax rotation. Four factors had eigenvalues greater than I; Factor I grouped Professional Efficacy items, Factor II grouped three Cynicism items. Further analysis was conducted to limit extraction to three factors. The factorial solution replicated the distribution of items in the questionnaire manual. Study results show that the Spanish version of the questionnaire is valid and reliable.


Inhibition of adenovirus infections by siRNA-mediated silencing of early and late adenoviral gene functions.
Adenoviruses are pathological agents inducing mild respiratory and gastrointestinal infections. Under certain circumstances, for example in immunosuppressed patients, they induce severe infections of the liver, heart and lung, sometimes leading to death. Currently, adenoviral infections are treated by palliative care with no curative antiviral therapy yet available. Gene silencing by RNA interference (RNAi) has been shown to be a potent new therapeutic option for antiviral therapy. In the present study, we examined the potential of RNAi-mediated inhibition of adenovirus 5 infection by the use of small interfering (si)RNAs targeting both early (E1A) and late (hexon, IVa2) adenoviral genes. Several of the initially analyzed siRNAs directed against E1A, hexon and IVa2 showed a distinct antiviral activity. Among them, one siRNA for each gene was selected and used for the further comparative investigations of their efficiency to silence adenoviruses. Silencing of the late genes was more efficient in inhibiting adenoviral replication than comparable silencing of the E1A early gene. A combination strategy involving down-regulation of any two or all three of the targeted genes did not result in an enhanced inhibition of viral replication as compared to the single siRNA approaches targeting the late genes. However, protection against adenovirus-mediated cytotoxicity was substantially improved by combining siRNAs against either of the two late genes with the siRNA against the E1A early gene. Thus, an enhanced anti-adenoviral efficiency of RNAi-based inhibition strategies can be achieved by co-silencing of early and late adenoviral genes, with down regulation of the E1A as a crucial factor.


A Bacterial Effector Mimics a Host HSP90 Client to Undermine Immunity.
The molecular chaperone HSP90 facilitates the folding of several client proteins, including innate immune receptors and protein kinases. HSP90 is an essential component of plant and animal immunity, yet pathogenic strategies that directly target the chaperone have not been described. Here, we identify the HopBF1 family of bacterial effectors as eukaryotic-specific HSP90 protein kinases. HopBF1 adopts a minimal protein kinase fold that is recognized by HSP90 as a host client. As a result, HopBF1 phosphorylates HSP90 to completely inhibit the chaperone's ATPase activity. We demonstrate that phosphorylation of HSP90 prevents activation of immune receptors that trigger the hypersensitive response in plants. Consequently, HopBF1-dependent phosphorylation of HSP90 is sufficient to induce severe disease symptoms in plants infected with the bacterial pathogen, Pseudomonas syringae. Collectively, our results uncover a family of bacterial effector kinases with toxin-like properties and reveal a previously unrecognized betrayal mechanism by which bacterial pathogens modulate host immunity.


[A case of squamous cell carcinoma of the urinary bladder effectively responsive to combination chemotherapy].
A case of invasive pure squamous cell carcinoma of the urinary bladder effectively responsive to combination chemotherapy in a 79-year-old female is reported. Clinical staging of the tumor was T3b. We used combination chemotherapy with methotrexate, peplomycin and cis-platinum (MBD regimen) before radical cystectomy. Remarkable regression of the tumor was identified by computed tomographic scan after one course of chemotherapy and the surgical specimen revealed no viable tumors. The patient has been very active in her daily life without evidence of local recurrence or metastasis for more than one year. Squamous cell carcinoma of the bladder generally is regarded as having a poor prognosis with 5-year survival rates ranging from 7.4 to 26% and effective chemotherapy has not yet been established. Our experience suggests that the cure rate of pure squamous cell carcinoma may be improved markedly by the use of MBD regimen.


Isolated latissimus dorsi transfer to restore shoulder external rotation in adults with brachial plexus injury.
In adults with brachial plexus injuries, lack of active external rotation at the shoulder is one of the most common residual deficits, significantly compromising upper limb function. There is a paucity of evidence to address this complex issue. We present our experience of isolated latissimus dorsi (LD) muscle transfer to achieve active external rotation. This is a retrospective review of 24 adult post-traumatic plexopathy patients who underwent isolated latissimus dorsi muscle transfer to restore external rotation of the shoulder between 1997 and 2010. All patients were male with a mean age of 34 years (21 to 57). All the patients underwent isolated LD muscle transfer using a standard technique to correct external rotational deficit. Outcome was assessed for improvement in active external rotation, arc of movement, muscle strength and return to work. The mean improvement in active external rotation from neutral was 24° (10° to 50°). The mean increase in arc of rotation was 52° (38° to 55°). Mean power of the external rotators was 3.5 Medical Research Council (MRC) grades (2 to 5). A total of 21 patients (88%) were back in work by the time of last follow up. Of these, 13 had returned to their pre-injury occupation. Isolated latissimus dorsi muscle transfer provides a simple and reliable method of restoring useful active external rotation in adults with brachial plexus injuries with internal rotational deformity.


Comparison of field portable measurements of ultrafine TiO2: X-ray fluorescence, laser-induced breakdown spectroscopy, and Fourier-transform infrared spectroscopy.
Laboratory measurements of ultrafine titanium dioxide (TiO2) particulate matter loaded on filters were made using three field portable methods (X-ray fluorescence (XRF), laser-induced breakdown spectroscopy (LIBS), and Fourier-transform infrared (FTIR) spectroscopy) to assess their potential for determining end-of-shift exposure. Ultrafine TiO2 particles were aerosolized and collected onto 37 mm polycarbonate track-etched (PCTE) filters in the range of 3 to 578 μg titanium (Ti). Limit of detection (LOD), limit of quantification (LOQ), and calibration fit were determined for each measurement method. The LOD's were 11.8, 0.032, and 108 μg Ti per filter, for XRF, LIBS, and FTIR, respectively and the LOQ's were 39.2, 0.11, and 361 μg Ti per filter, respectively. The XRF calibration curve was linear over the widest dynamic range, up to the maximum loading tested (578 μg Ti per filter). LIBS was more sensitive but, due to the sample preparation method, the highest loaded filter measurable was 252 μg Ti per filter. XRF and LIBS had good predictability measured by regressing the predicted mass to the gravimetric mass on the filter. XRF and LIBS produced overestimations of 4% and 2%, respectively, with coefficients of determination (R(2)) of 0.995 and 0.998. FTIR measurements were less dependable due to interference from the PCTE filter media and overestimated mass by 2% with an R(2) of 0.831.


Basis of electrical stimulation of the cochlea and the cochlear nucleus.
Sensorineural hearing loss is the most common form of deafness in humans. In patients with a severe-profound sensorineural hearing loss therapeutic intervention can only be achieved by direct electrical stimulation of the auditory nerve via a cochlear implant, or - in cases where a cochlear implant is not a surgical option - neurons within the central auditory pathway via an auditory brainstem implant. This paper reviews the basis of electrical stimulation of these structures with an emphasis on pathophysiology and safety.


Effects of High Atmospheric CO(2) and Sink Size on Rates of Photosynthesis of a Soybean Cultivar.
The effect of sink strength on photosynthetic rates under conditions of long-term exposure to high CO(2) has been investigated in soybean. Soybean plants (Merr. cv. Fiskeby V) were grown in growth chambers containing 350 microliters CO(2) per liter air until pod set. At that time, plants were trimmed to three trifoliolate leaves and either 21 pods (high sink treatment) or 6 pods (low sink treatment). Trimmed plants were either left in 350 microliters CO(2) per liter of air or placed in 1000 microliters CO(2) per liter of air (high CO(2) treatment) until pod maturity. Whole plant net photosynthetic rates of all plants were measured twice weekly, both at 350 microliters CO(2) per liter of air and 1000 microliters CO(2) per liter of air. Plants were also harvested at this time for dry weight measurements. Photosynthetic rates of high sink plants at both measurement CO(2) concentrations were consistently higher than those of low sink plants, and those of plants given the 350 microliter CO(2) per liter of air treatment were higher at both measurement CO(2) concentrations than those of plants given the 1000 microliters CO(2) per liter of air treatment. When plants were measured under treatment CO(2) levels, however, rates were higher in 1,000 microliter plants than 350 microliter CO(2) plants. Dry weights of all plant parts were higher in the 1,000 microliters CO(2) per liter air treatment than in the 350 microliters CO(2) per liter air treatment, and were higher in the low sink than in the high sink treatments.


IgA antigliadin antibodies as a screening method for nonovert celiac disease in children with insulin-dependent diabetes mellitus.
One hundred forty-one children with insulin-dependent diabetes mellitus were screened for serum immunoglobulin A (IgA) antigliadin antibodies by means of an enzyme-linked immunosorbent assay (ELISA) method. None of them had gastrointestinal symptoms, and no major nutritional disturbances were detected except for a girl with moderate growth delay. Twelve patients with positive IgA antigliadin antibodies on two or more consecutive measurements underwent a small intestinal biopsy; four of them had a subtotal villous atrophy, and celiac disease was diagnosed; in another patient, a partial villous atrophy was observed. Children suffering from both diabetes and celiac disease showed an onset of diabetes at a younger age than did nonceliac patients. Prevalence of celiac disease in the screened population is 2.85%, which is higher than in the general population of the Comunidad Valenciana (one in 2,500 live births).


Preparing Medical Students for the Final Examinations During the COVID-19 Crisis: A Bumpy Ride to the Finishing Line.
In this viewpoint, we share and reflect on the experiences of final-year students preparing for a high-stakes examination at the Faculty of Medicine, Universiti Kebangsaan Malaysia during the COVID-19 pandemic. We highlight the new challenges faced during web-based remote learning and major differences in the clinical learning environment at our teaching hospital, which was one of the designated COVID-19 centers in Malaysia. We also document how a face-to-face professional examination was conducted for final-year medical students at our institution despite in times of a global health crisis. The lessons learned throughout this process address the importance of resilience and adaptability in unprecedented times. Further, we recommend appropriate measures that could be applied by medical schools across the world to improve the delivery of quality medical education during a crisis in the years to come.


The effects of electrical stimulation of normal abductor digiti quinti on strength.
This pilot study investigated the effectiveness of electrical stimulation in strengthening normal abductor digiti quinti muscle. The abductor digiti quinti (AbDQ) muscle is unique as it may be considered atrophic but otherwise normal muscle tissue. Eight healthy subjects participated in this investigation and they were randomly divided into two groups. Group A (N = 4) received intermittent electrical stimulation with an on-off time ratio of 1:3. Group B (N = 4) received intermittent electrical stimulation with an on-off ratio of 1:2. The control group C (N = 8) was the nonelectrically stimulated foot of each participant. Each subject received 20 treatments of electrical stimulation of 1 hour duration, 5 days/week for 4 weeks. At the conclusion of the 20 sessions, significant improvements (P < 0.0 1) in functional strength were noted in the stimulated groups (1 17.9%); the control group improved 9.9%. The data demonstrated that electrical stimulation produced increases in the functional strength of the AbDQ. J Orthop Sports Phys Ther 1985;6(6):343-346.


When the political becomes personal: Reflecting on disability bioethics.
A discussion of the connection between activism and academia in bioethics, highlighting the author's own trajectory, exploring the extent to which academics have an obliation to be 'judges' rather than 'barristers' (as explored by Jonathan Haidt) and asking questions about the relationship of disability to positions in bioethics.


Molecular cloning and primary structure of Kell blood group protein.
The Kell blood group is a major antigenic system in human erythrocytes. Kell antigens reside on a 93-kDa membrane glycoprotein that is surface-exposed and associated with the underlying cytoskeleton. We isolated tryptic peptides and, based on the amino acid sequence of one of the peptides and by using the PCR, prepared a specific oligonucleotide to screen a lambda gt10 human bone-marrow cDNA library. Four clones were isolated, one containing cDNA with an open reading frame for an 83-kDa protein. All known Kell amino acid sequences were present in the deduced sequence; moreover, rabbit antibody to a 30-amino acid peptide, prepared from this sequence, reacted on an immunoblot with authentic Kell protein. The Kell cDNA sequence predicts a 732-amino acid protein. Hydropathy analysis indicates a single membrane-spanning region, suggesting that Kell protein is oriented with 47 of its N-terminal amino acids in the cell cytoplasm, and a 665-amino acid segment, which contains six possible N-glycosylation sites, is located extracellularly. Computer-based search showed that Kell has structural and sequence homology to a family of zinc metalloglycoproteins with neutral endopeptidase activity.


[Study of asymmetries in the severe antero-posterior disharmonies].
Using the Treil 14 points cephalometric model orthodontists can prepare a complete cranio-facial anatomic assessment at three analytic levels: the framework or envelope, the basal bone and the alveolo-dental arcade. The assessment of border-line surgical antero-posterior dysmorphosis can elucidate interesting depictions of asymmetries, their relation to other malformities, and their genesis. Asymmetry arises from over-growth of one side of the face in all three dimensions of space even if, clinically, it often appears that one dimension is predominately affected. The ortho-morphic cases of Angle Class I present a little right excess or "natural" asymmetry. The Class III cases present a severe excess on the right side, while the Class II cases present an excess on the left side comparing with reference sample.


Self-management strategies and comorbidities in chronic disease patients: associations with quality of life and depression.
Self-management strategies are essential for improving prognosis in chronic illnesses. This study aimed to investigate the association between comorbidity and self-management strategies. A total of 700 patients with one or more chronic diseases including diabetes, dyslipidemia, hypertension, osteoporosis, chronic lung disease, chronic kidney disease and arthritis were enrolled. A questionnaire including the Smart Management Strategy for Health Assessment Tool Short Form (SAT), the Short Form-12, the McGill Quality of Life questionnaire, and the Patient Health Questionnaire-9 was administered to participants. The trend of each SAT according to number of comorbidities was evaluated, and the difference in quality of life and depression according to self-management strategies was examined in the model classified by the number of diseases. Self-management strategy scores tended to decrease as the number of comorbidities increased from one to four (p-value: 0.001 to 0.008). Regardless of the number of comorbidities, the MQOL score was higher in the good self-management strategy group (p: <0.001 to 0.016). The prevalence of mild depression was higher in patients with low self-management strategy, but the differences were not significant. Based on these findings, self-management strategies should be evaluated multidimensionally, and patients should be encouraged to develop effective self-management strategies to manage multiple chronic diseases.


Objective assessment of subjective tinnitus through contralateral suppression of otoacoustic emissions by white noise; suggested cut-off points.
Normative otoacoustic emission (OAE) suppression values are currently lacking and the role of cochlear efferent innervation in tinnitus is controversial. The aim of this study was to investigate the association between tinnitus and medial olivocochlear bundle (MOCB) malfunction. Potential suppression amplitude cut-off criteria that could differentiate participants with tinnitus from those without were sought. Mean suppression amplitudes of transient evoked OAEs and distortion product OAEs by contralateral white noise (50 dBSL) were recorded. Six mean suppression amplitudes criteria were validated as possible cut-off points. The population consisted of normal hearing (n = 78) or presbycusic adults (n = 19) with tinnitus or without (n = 28 and 13, respectively) chronic tinnitus (in total, n = 138 78 females/60males, aged 49 ± 14 years). Participants with mean suppression values lower than 0.5-1 dBSPL seem to present a high probability to report tinnitus (specificity 88-97%). On the other hand, participants with mean suppression values larger than 2-2.5dBSPL seem to present a high probability of the absence of tinnitus (sensitivity 87-99%). Correlations were stronger among participants with bilateral presence or absence of tinnitus. This study seem to confirm an association between tinnitus and low suppression amplitudes (<1 dBSPL), which might evolve into an objective examination tool, supplementary to conventional audiological testing.


Rovibronically selected and resolved two-color laser photoionization and photoelectron study of nickel carbide cation.
We have performed a two-color laser photoionization and photoelectron study of nickel carbide (NiC) and its cation (NiC(+)). By preparing NiC in a single rovibronic level of an intermediate vibronic state via visible laser excitation prior to ultraviolet laser photoionization, we have measured the photoionization efficiency spectrum of NiC near its ionization threshold, covering the formation of NiC(+)(X (2)Sigma(+);v(+)=0-3). We have also obtained well-resolved rotational transitions for the v(+)=0 and 1 vibrational bands of the NiC(+)(X (2)Sigma(+)) ground state. The assignment of rotational transitions observed between the neutral NiC intermediate state and the NiC(+) ion ground state has allowed the direct determination of a highly precise value for the ionization energy of NiC, IE(NiC)=67,525.1+/-0.5 cm(-1) (8.372 05+/-0.000 06 eV). This experiment also provides reliable values for the vibrational spacing [DeltaG(1/2)=859.5+/-0.5 cm(-1)], rotational constants (B(e)(+)=0.6395+/-0.0018 cm(-1) and alpha(e)(+)=0.0097+/-0.0009 cm(-1)), and equilibrium bond distance (r(e)(+)=1.628 A) for the NiC(+)(X (2)Sigma(+)) ground state. The experimental results presented here are valuable for benchmarking the development of more reliable ab initio quantum computation procedures for energetic and spectroscopic calculations of transition metal-containing molecules.


Leptin in acute myocardial infarction and period of convalescence in patients with type 2 diabetes mellitus.
Leptin is a protein produced in adipose tissue and takes part in angiogenesis and atherogenesis. Leptin is associated with development of type 2 diabetes and cardiovascular disease. To evaluate leptin concentrations in acute myocardial infarction and in the period of convalescence in patients with type 2 diabetes mellitus. Coronary angiography was performed in 58 patients with acute myocardial infarction. The study group comprised 35 patients with type 2 diabetes mellitus (DM) (25 men, 10 women, mean age 63.8 + or - 11.5 years) and 23 non-diabetic subjects (17 men, 6 women, mean age 58.6 + or - 9.9 years) - the control group. All patients underwent medical examination and body mass indices (BMI) as well as waist/hip ratios (WHR) were calculated. Venous blood was collected after 24 hours of admission (second day), on day 5 and three weeks after admission. Leptin level was significantly associated with BMI (DM: r = 0.46, p = 0.005; control group: r = 0.67, p < 0.01), and hip circumference (DM: r = 0.28, p = 0.09; control group: r = 0.41, p = 0.04). Plasma leptin levels in women with type 2 diabetes were higher than in men (32.1 + or - 11.7 microg/mL vs 12.7 + or - 11.2 microg/mL, p < 0.01). Plasma leptin levels were significantly lower in non-diabetics compared to diabetic patients. Plasma leptin levels in diabetic patients were significantly higher in the acute phase of myocardial infarction than in the period of convalescence (18.3 + or - 14.3 microg/mL, 16.1 + or - 12.8 microg/mL, 14.8 + or - + or - 11.2 microg/mL, p = 0.02) but not in the control group (10.6 + or - 8.2 microg/mL, 10.0 + or - 7.3 microg/mL, 9.6 + or - 7.0 microg/mL, NS). Plasma leptin levels in diabetic patients were significantly higher in the acute myocardial infarction than in the period of convalescence. These findings suggests that leptin may play an important role in the metabolic changes taking place during the first days of myocardial infarction.


Changes in inositol phosphate metabolism are associated with terminal differentiation and neoplasia in mouse keratinocytes.
Cultured murine keratinocytes respond to specific Ca2+ levels in medium (Ca0) by expressing markers of terminal differentiation. A Ca0 of 0.05 mM selects for a basal cell phenotype, whereas spinous cell characteristics occur in 0.12 mM Ca2+ and cornified envelopes develop in 1.0 mM Ca2+. An increase in inositol phosphate (InsP) metabolism is associated with higher Ca2+ in the medium. The magnitude of Ca(2+)-stimulated InsP turnover is Ca0-dependent, whereas Ca0 of 0.05, 0.12 or 1.4 mM resulted in a graded, sustained (greater than 24 h) increase in InsPs. Diacylglycerol (DAG) levels similarly increased in a graded manner. The major inositol trisphosphate (InsP3) to accumulate was Ins-1,3,4-P3 while Ins-1,4,5-P3 increased transiently. Neoplastic keratinocyte cell lines, 308 and SP-1, which produce benign tumors and have a mutated c-rasHa gene, do not express markers of differentiation in response to Ca2+. Basal InsP and DAG are 2- and 5-fold higher respectively in the neoplastic cells relative to normal keratinocytes. However, the metabolic profiles of InsPs were similar in normal and neoplastic cells. In neoplastic cells, InsP metabolism was stimulated even further following a Ca2+ increase, and this was graded to the Ca0. The unusual, sustained Ca(2+)-graded InsP response in normal cells is consistent with the turnover of InsP contributing to the signals controlling expression of markers of differentiation. Very high InsP turnover and DAG levels, as in neoplastic cells, may be inhibitory to marker expression.


Neurokinin-1 receptor-expressing neurons in the ventral medulla are essential for normal central and peripheral chemoreception in the conscious rat.
Neurokinin-1 receptor immunoreactive (NK1R-ir) neurons and processes are widely distributed within the medulla, prominently at central chemoreceptor sites. Focal lesions of NK1R-ir neurons in the medullary raphe or the retrotrapezoid nucleus partially reduced the CO(2) response in conscious rats. We ask if NK1R-ir cells and processes over a wide region of the ventral medulla are essential for central and peripheral chemoreception by cisterna magna injection of SSP-SAP, a high-affinity version of substance P-saporin. After 22 days, NK1R-ir cell loss was -79% in the retrotrapezoid nucleus and -65% in the A5 region, which lie close to the ventral surface, and -38% in the medullary raphe and -49% in the pre-Bötzinger complex/rostral ventral respiratory group, which lie deeper. Dorsal chemoreceptor sites, the caudal nucleus tractus solitarius and the A6 region, were unaffected. At 8 and 22 days, these lesions produced 1) hypoventilation during air breathing in wakefulness ( approximately 8%) and in non-rapid eye movement (NREM) ( approximately 9%) and rapid eye movement ( approximately 14%) sleep, as measured over a 4-h period; 2) a substantially reduced ventilatory response to 7% CO(2) by 61% in wakefulness and 46-57% in NREM sleep; and 3) a decreased ventilatory response to 12% O(2) by 40% in wakefulness and 35% in NREM sleep at 8 days, with partial recovery by 22 days. NK1R-ir neurons in the ventral medulla are essential for normal central chemoreception, provide a drive to breathe, and modulate the peripheral chemoreceptor responses. These effects are not state dependent.


Production of tomato flavor volatiles from a crude enzyme preparation using a hollow-fiber reactor.
In recent years there has been an increase in the interest in the production of compounds by isolation from natural sources or through processes that can be deemed "natural". This is of particular interest in the food and beverage industry for flavors and aromas. Hexanal, organoleptically known to possess "green character", is of considerable commercial interest. The objective of this study was to determine if the enzyme template known to be responsible for the synthesis of hexanal from linoleic acid (18:2) in tomato fruits could be harnessed using a hollow-fiber reactor. A hollow-fiber reactor system was set up and consisted of a XAMPLER ultrafiltration module coupled to a reservoir. The enzyme template was extracted from ripe tomato fruits and processed through an ultrafiltration unit (NMWC of 100 kDa) to produce a retentate enriched in soluble and membrane-associated lipoxygenase (LOX) and hydroperoxide lyase (HPL). This extract was recirculated through the lumen of the hollow-fiber ultrafiltration unit with the addition of substrate in the form of linoleic acid, with buffer addition to the reaction flask to maintain a constant retentate volume. Product formation was measured in the permeate using solid phase microextraction (SPME) developed for this system. At exogenous substrate concentrations of 16 mM and a transmembrane pressure of 70 kPa, hexanal production rates are in the order of 5.1 microg/min. Addition of Triton X-100 resulted in membrane fouling and reduced flux. The reactor system has been run for periods of up to 1 week and has been shown to be stable over this period.


[Fixed-dose combination therapy: reduction of side effects with enhanced tolerance and antihypertensive efficacy].
Despite the availability of many newer antihypertensive agents, hypertensive patients remain at a higher risk of premature death than the general population. This persistence of elevated morbidity and mortality may be accounted for by the frequent failure to achieve adequate blood pressure reduction despite an extensive range of available antihypertensive agents. Such considerations have led to the reassessment of the potential role of fixed-dose combination agents. The antihypertensive efficacy may be enhanced when two classes of agents are combined. In addition, combination therapy enhances tolerability because one drug of fixed combination can antagonize some of the adverse effects of the second drug. Fixed-dose combination therapy simplifies the treatment regimen, preventing treatment failures that might result from missed doses.


Lifestyles Associated With Human Semen Quality: Results From MARHCS Cohort Study in Chongqing, China.
Decline of semen quality in past decades is suggested to be potentially associated with environmental and sociopsychobehavioral factors, but data from population-based cohort studies is limited. The male reproductive health in Chongqing College students (MARHCS) study was established in June 2013 as a perspective cohort study that recruited voluntary male healthy college students from 3 universities in Chongqing. The primary objectives of the MARHCS study are to investigate the associations of male reproductive health in young adults with sociopsychobehavioral factors, as well as changes of environmental exposure due to the relocation from rural campus (in University Town) to metro-campus (in central downtown). A 93-item questionnaire was used to collect sociopsychobehavioral information in manner of interviewer-interviewing, and blood, urine and semen samples were collected at the same time. The study was initiated with 796 healthy young men screened from 872 participants, with a median age of 20. About 81.8% of this population met the WHO 2010 criteria on semen quality given to the 6 routine parameters. Decreases of 12.7%, 19.8%, and 17.0%, and decreases of 7.7%, 17.6%, and 14.7% in total sperm count and sperm concentration, respectively, were found to be associated with the tertiles of accumulated smoking amount. Fried food consumption (1-2 times/wk or ≥3 times/wk vs nonconsumers) was found to be associated with decreased total sperm count (10.2% or 24.5%) and sperm concentration (13.7% or 17.2%), respectively. Coffee consumption was found to be associated with increased progressive and nonprogressive motility of 8.9% or 15.4% for subjects consuming 1-2 cups/wk or ≥3 cups/wk of coffee, respectively. Cola consumption appeared an association with decreased semen volume at 4.1% or 12.5% for 1-2 bottles/wk or ≥3 bottles/wk. A cohort to investigate the effects of environmental/sociopsychobehavioral factors act on semen quality was successfully set up. We found smoking, coffee/cola/fried foods consumption to be significantly associated with semen quality from the baseline investigation.


Angular-momentum-induced phase transition in spherical gravitational systems: N-body simulations.
The role of thermodynamics in the evolution of systems evolving under purely gravitational forces is not completely established. Both the infinite range and singularity in the Newtonian force law preclude the use of standard techniques. However, astronomical observations of globular clusters suggest that they may exist in distinct thermodynamic phases. Here, using dynamical simulation, we investigate a model gravitational system that exhibits a phase transition in the mean-field limit. The system consists of rotating, concentric, mass shells of fixed angular-momentum magnitude and shares identical equilibrium properties with a three-dimensional point mass system satisfying the same condition. The mean-field results show that a global entropy maximum exists for the model, and a first order phase transition takes place between "quasi-uniform" and "core-halo" states, in both the microcanonical and canonical ensembles. Here we investigate the evolution and, with time averaging, the equilibrium properties of the isolated system. Simulations were carried out in the transition region, at the critical point, and in each clearly defined thermodynamic phase, and striking differences were found in each case. We find full agreement with mean-field theory when finite-size scaling is accounted for. In addition, we find that (1) equilibration obeys power-law behavior, (2) virialization, equilibration, and the decay of correlations in both position and time, are very slow in the transition region, suggesting that the system is also spending time in the metastable phase, and (3) there is a strong evidence of long-lived, collective oscillations in the supercritical region.


A new nonpharmacological method in fibromyalgia: the use of wool.
The aim was to assess the effect of wool use in patients with fibromyalgia. Various studies concerning the treatment of patients with fibromyalgia using nonpharmacological methods have been carried out. There are, however, no reports on the use of wool clothing and bedding in treating these patients. The study employed two-group, experimental design. A total of 50 patients with fibromyalgia, based on the criteria of the American College of Rheumatology, were selected for the study. They were distributed equally into two groups: a control group and a treatment group. The 25 patients in each group were randomly selected and the compositions of the two groups were statistically identical. The patients in the treatment group wore woolen underwear (which covered the body from the shoulders to the thighs) and used woolen bedding such as woolen bed liner, woolen quilt and pillow during the experimental period of 6 weeks. All patients were assessed at the beginning the trial (pre-test) and the end of 6th (post-test) week. Data were collected using the visual analogue scale (0-10), tender points count, and Fibromyalgia Impact Questionnaire. Patients in the treatment group reported significant improvements in their conditions including a reduction in pain levels, tender point counts, and all scores of the Fibromyalgia Impact Questionnaire (p <or= 0.001). The use of woolen underwear and woolen bedding were effective in reducing the symptoms of patients suffering from fibromyalgia. The use of wool is recommended as a means of treatment for alleviating the pain of fibromyalgia. Nurses provide professional support to patients with fibromyalgia. They select suitable clothes and sleeping materials for their patients with this object in mind: to keep their patients warm and to protect them from the cold.


Linagliptin versus sitagliptin in patients with type 2 diabetes mellitus: a network meta-analysis of randomized clinical trials.
Diabetes is one of the most common chronic and costly diseases worldwide and type 2 diabetes is the most common type which accounts for about 90% of cases with diabetes. New medication-therapy regimens such as those containing linagliptin alone or in combination with other medications (within the category of DDP-4 inhibitors) must be evaluated in terms of efficacy and compared with other currently used drugs and then enter the medication list of the country. Hence, this study aimed to compare the clinical efficacy of the two drugs, i.e. linagliptin and sitagliptin, in patients with type 2 diabetes. A systematic review was conducted to identify all clinical trials published by 2015 which compared the two drugs in patients with type 2 diabetes. Using keywords such as "linagliptin", "type 2 diabetes mellitus", "sitagliptin" and related combinations, we searched databases including Scopus, PubMed, and Web of Science. The quality of the selected studies was evaluated using the Jadad score. Considering primary and secondary outcomes extracted from the reviewed studies, a network meta-analysis was used to conduct a systematic comparison between the two studied drugs. This network meta-analysis included 32 studies (Linagliptin vs PLB: n = 8, Sitagliptin vs PLB: n = 13, Linagliptin + MET vs PLB + MET: n = 4, and Sitagliptin + MET vs PLB + MET: n = 7) and a total of 13,747 patients. The results showed no significant difference between linagliptin and sitagliptin in terms of key efficacy and safety outcomes such as HbA1c changes from baseline, body weight change from baseline, percentage of patients achieving HbA1c <7, and percentage of patients experiencing hypoglycemic events (p > 0.05). The results showed that the efficacy of the two drug regimens was the same. Based on the results, there was no significant difference between the two drugs, i.e. linagliptin and sitagliptin, in terms of efficacy; in other words, the efficacy of the two drugs was the same. Therefore, the use of these two drugs depends on their availability and cost. Graphical abstract of the network meta-analysis performed to evaluate the alternatives under the study.


Time Course of Lens Epithelial Cell Behavior in Rabbit Eyes following Lens Extraction and Implantation of Intraocular Lens.
After cataract surgery, some lens epithelial cells (LECs) transdifferentiate into myofibroblast-like cells, which causes fibric posterior capsule opacification (PCO). Residual LECs differentiate into lens fiber cells, forming Elschnig pearls with PCO. This study was carried out to identify the time course of both types of LEC behavior in rabbit eyes following lens extraction and implantation of an intraocular lens (IOL). Phacoemulsification and implantation of posterior chamber IOLs were performed in rabbit eyes. Following enucleation, immunohistochemical methods were used to detect α-smooth muscle actin (α-SMA), a marker for myofibroblast-like cells, in the pseudophakic rabbit eyes. A mouse monoclonal antibody against α-SMA was used. Soon after the operation, the LECs migrated and covered the lens capsule. Thereafter, the LECs around the anterior capsular margin were always positive for α-SMA. However, the distributions of these cells were not consistent. In some specimens, α-SMA-positive LECs were present around the IOL optic early after surgery, but most of them had disappeared several weeks after the surgery. The residual cells induced fibrotic PCO. In the other specimens, most LECs around the IOL optic except the anterior capsular margin were negative for α-SMA. In the peripheral region covered by the peripheral anterior and posterior capsules, LECs on the posterior capsule always differentiated into lens fiber cells and formed a Soemmering ring. Thereafter, migration of lens fiber cells from the Soemmering ring and differentiation of LECs in situ on the central posterior capsule consisted of Elschnig pearls type of PCO. Although postoperative LEC behavior is not consistent, residual α-SMA-positive LECs induced fibrotic PCO. The lens fiber cells that migrated from the peripheral capsular bag or that were differentiated in situ covered the central posterior capsule, forming Elschnig pearls with PCO.


Mothering and acculturation: experiences during pregnancy and childrearing of Filipina mothers married to Japanese.
This study aims to describe the lived experiences of Filipina mothers married to Japanese during pregnancy and childrearing. Eight focus group interviews (FGI) were conducted among 39 Filipino mothers who are currently residing in Japan to obtain significant information with regard to their pregnancy and childrearing experiences. Content analysis was used to extract relevant themes that will describe the experiences of this group of migrant mothers. The findings revealed three major themes: 1) cultural barriers during pregnancy and childrearing; 2) mothering at the different stages of childrearing; and 3) positive adjustments to a new role in a new environment. The establishment of means of communication with migrant mothers effectively enabling them to understand important information for promoting healthy pregnancy and childrearing is strongly recommended. Provision of school information in the English language and enhancing the resilient character of the Filipina are important strategies in promoting positive pregnancy and childrearing experiences among Filipina migrant mothers.


[A man with discoloration of his lower legs].
A 73-year-old man consulted his general practitioner with a non-itchy rash on his lower legs, which developed a few hours after golfing. We saw a blotchy, red, non-blanchable discoloration with some blisters. Microscopic examination showed dermal inflammatory infiltrate with minor vessel wall damage and extravasation of erythrocytes. Diagnosis: exercise-induced vasculitis.