Comparison study of OCT, HRT and VF findings among normal controls and patients with pseudoexfoliation, with or without increased IOP.
To compare and evaluate optic nerve head (ONH) and retinal nerve fiber layer (RNFL) measurements obtained with the optical coherence tomography (OCT) and the Heidelberg retina tomography (HRT) to visual field (VF) parameters in normal and in patients with pseudoexfoliation with or without increased intraocular pressure (IOP). A total of 96 subjects were included in our study aged between 65 years and 78 years. The normal group consisted of 28 subjects (14 men and 14 women). Out of the total number of patients, 68 patients who showed pseudoexfoliation (21 men and 47 women) were divided into two groups. Of these, the first group had pseudoexfoliation with increased IOP and the second group showed deposits of pseudoexfoliative material without an increase in IOP. The normal controls were randomly chosen and restricted to those without any glaucomatous optic disc damages, VF defects, and an IOP <15 mmHg. All subjects were prospectively included for repeated measurements of IOP, OCT, HRT, and VFs during the same visit by the same examiner and all measurements were repeated every 3 months. Mean RNFL thickness measured by OCT was larger in the normal controls than in the other two groups (98.04 μm (first group) vs 75.42 μm and 97.02 μm (second group), P<0.05). Four-quadrant RNFL thickness measurements were significantly different between the normal and the group 1 (P<0.05) but not with the group 2 (P>0.05). Rim area had a mean difference of -0.44, whereas cup-to-disc ratio (C/D) showed a mean difference of 0.31, thus being significantly different between the normal and the two groups (all P<0.05). The median of the mean deviation parameter of VFs was -0.28 for the normal vs -0.32 and -0.18 for the other two groups, whereas pattern standard deviation median difference was 0.89 for the normal and 1.32 and 1.20 for the other two groups, respectively (P<0.05). Both OCT and HRT showed early ONH and RNFL changes in their parameters and did not correlate with the normal findings of the automated perimetry.


Letting the cat out of the bag: a personal journey in Biophysics.
When the author arrived in Berkeley, in the mid 1970s, to study Biophysics he soon felt as if he was engaging himself in a somewhat marginal activity. Biology was then entering another of its cyclical periods of annotation that was to culminate with the human genome project. Two decades later, however, at the end of this process, it had become clear that two main tasks were acquiring a central importance in biological research: a renewed push for a quantitative, precise description of biological systems at the molecular level, and efforts towards an integrated understanding of the operation, control, and coordination of cellular processes. Today, these have become two of the most fertile research areas in Biophysics.


Types, distribution, and seasonal occurrence of sounds attributed to Bryde's whales (Balaenoptera edeni) recorded in the eastern tropical Pacific, 1999-2001.
Vocalizations resembling known Bryde's whale sounds were recorded on autonomous hydrophones at seven sites in the eastern tropical Pacific. Five short (<3 s) low-frequency (<80 Hz) "phrase" types were observed. "Swept alternating tonal" phrases included a 37-Hz tone and often a 25-16-Hz downswept tone, while "nonswept alternating tonal" phrases had a predominant tone at 29 Hz and often additional tones at 16 and 47 Hz. Alternating tonal phrases were found in 79% of the total hours in which phrases were detected, and occurred primarily at the eastern hydrophone sites. "Burst-tonal" phrases included tones that were often preceded by a wideband burst of noise. The "low burst-tonal" phrase contained tones at 19 and 30 Hz, and was detected at five of the hydrophone sites. The "high burst-tonal" phrase included a 42-Hz tone and was observed only on the northwestern hydrophones. A single "harmonic tone" phrase type was observed that included a fundamental tone at 26 Hz and at least two harmonics; this phrase was observed exclusively at the eastern hydrophone stations. This opportunistic survey has shown that acoustics is an effective means of studying this poorly understood, pelagic balaenopterid.


Borane-Catalyzed, Chemoselective Reduction and Hydrofunctionalization of Enones Enabled by B-O Transborylation.
The use of stoichiometric organoborane reductants in organic synthesis is well established. Here these reagents have been rendered catalytic through an isodesmic B-O/B-H transborylation applied in the borane-catalyzed, chemoselective alkene reduction and formal hydrofunctionalization of enones. The reaction was found to proceed by a 1,4-hydroboration of the enone and B-O/B-H transborylation with HBpin, enabling catalyst turnover. Single-turnover and isotopic labeling experiments supported the proposed mechanism of catalysis with 1,4-hydroboration and B-O/B-H transborylation as key steps.


Trigonelline prevents kidney stone formation processes by inhibiting calcium oxalate crystallization, growth and crystal-cell adhesion, and downregulating crystal receptors.
Trigonelline is the second most abundant bioactive alkaloid found in coffee. It is classified as a phytoestrogen with similar structure as of estradiol and exhibits an estrogenic effect. A previous study has reported that fenugreek seed extract rich with trigonelline can reduce renal crystal deposition in ethylene glycol-induced nephrolithiatic rats. However, direct evidence of such anti-lithogenic effects of trigonelline and underlying mechanisms have not previously been reported. Our study therefore addressed the protective effects and mechanisms of trigonelline against kidney stone-forming processes using crystallization, crystal growth, aggregation and crystal-cell adhesion assays. Also, proteomics was applied to identify changes in receptors for calcium oxalate monohydrate (COM), the most common stone-forming crystal, on apical membranes of trigonelline-treated renal tubular cells. The analyses revealed that trigonelline significantly reduced COM crystal size, number and mass during crystallization. Additionally, trigonelline dose-dependently inhibited crystal growth and crystal-cell adhesion, but did not affect crystal aggregation. Mass spectrometric protein identification showed the smaller number of COM crystal receptors on apical membranes of the trigonelline-treated cells. Western blotting confirmed the decreased levels of some of these crystal receptors by trigonelline. These data highlight the protective mechanisms of trigonelline against kidney stone development by inhibiting COM crystallization, crystal growth and crystal-cell adhesion via downregulation of the crystal receptors on apical membranes of renal tubular cells.


[A case of rectal endocrine cell carcinoma treated by laparoscopic assisted intersphincteric resection after neoadjuvant chemotherapy].
A 51-year-old male patient visited our hospital with a complaint of anal dysfunction and anal pain. Colonoscopy revealed a lower rectal cancer just above the dentate line, and its biopsy showed endocrine cell carcinoma. Enhanced computed tomography( CT) showed pararectal and right inguinal lymph node metastasis. Leucovorin, 5-fluorouracil, and oxaliplatin (FOLFOX) therapy was initiated first; then, after K-RAS was found to be wild type, 6 courses of FOLFOX plus panitumumab were administered. After the chemotherapy, the main tumor and the lymph node swelling reduced evidently. Its effect was judged as a partial response (PR). Laparoscopic assisted intersphincteric resection, right inguinal lymph node dissection, and temporary ileostomy were performed. The pathology revealed endocrine cell carcinoma (MP, ly2, v2, n0, stage II). Its pathological effect was judged as Grade 1b. Five months after the surgery, the ileostomy was closed.


Prognostic Significance of Presenting Blood Pressure in Patients With ST-Elevation Myocardial Infarction Undergoing Percutaneous Coronary Intervention.
We evaluated the impact of normal vs. high presenting blood pressure (BP) on clinical outcomes and cardiac function in patients with ST-elevation myocardial infarction (MI). In 11,292 patients, in-hospital mortality and major adverse clinical events (MACE; all-cause death, nonfatal MI, or any revascularization) during follow-up were compared between patients with normal (≥ 100 mm Hg and ≤ 139 mm Hg) and high (≥ 140 mm Hg) systolic BP at presentation. Compared to patients with high BP, patients with normal BP had significantly higher in-hospital mortality (1.5% vs. 3.7%; P < 0.001), especially in those with prior hypertension, and higher rates of all-cause death (3.3% vs. 5.3%; P < 0.001) and MACE (9.8% vs. 11.8%; P = 0.04) during follow-up (median: 330 days). After multivariate adjustment, normal BP was associated with higher risk of in-hospital mortality (adjusted hazard ratio (HR) = 2.268; 95% confidence interval (CI) = 1.144-4.498; P = 0.019), but not all-cause death (adjusted HR = 0.956; 95% CI = 0.602-1.517) or MACE (adjusted HR = 0.935; 95% CI = 0.755-1.158). Left ventricular ejection fraction at baseline and follow-up was significantly lower in patients with normal BP (52% vs. 51%; P < 0.001 and 55% vs. 54%; P = 0.018, respectively). Our findings indicate that patients with normal presenting BP, especially those with prior hypertension, exhibit higher in-hospital mortality and poorer cardiac function compared to patients with high BP. Although outcomes during follow-up did not differ, cardiac function was persistently poorer in patients who presented with normal BP.


Presumed Solitary Circumscribed Retinal Astrocytic Proliferation in the Fovea With OCT Angiography: A Misnomer.
The retinal lesion known as the presumed solitary circumscribed retinal astrocytic proliferation (pSCRAP) is a benign retinal tumor. Although many of the clinical characteristics of the lesion have been described, much about the pathogenesis of this uncommon tumor is not yet known. Here, the authors report a pSCRAP lesion in the fovea with secondary vision loss occurring in middle age. Structural optical coherence tomography (OCT) scans indicate that the lesion arises from the deep retina or retinal pigment epithelium (RPE), whereas OCT angiography characteristics of the lesion show a lack of intrinsic or paralesional vascular flow, indicating that this lesion is fibrous and likely derived from the RPE or deep retina and not the retinal astrocytes. [Ophthalmic Surg Lasers Imaging Retina. 2018;49:212-214.].


Immersion Mirau interferometry for label-free live cell imaging in an epi-illumination geometry.
In cell biology studies it is often important to avoid the damaging effects caused by fluorescent stains or UV-light. Immersion Mirau Interferometry (IMI) is an epi-illumination label-free imaging technique developed at the Columbia University Radiological Research Accelerator Facility. It is based on the principles of phase-shifting interferometry (PSI) and represents a novel approach for interferometric imaging of living cells in medium. To accommodate the use of medium, a custom immersion Mirau interferometric attachment was designed and built in-house. The space between the reference mirror and the beam splitter is filled with liquid to ensure identical optical paths in the test and reference arms. The interferometer is mountable onto a microscope objective. The greatest limitation of standard PSI is the sensitivity to environmental vibrations, because it requires consecutive acquisition of several interferograms. We are developing Simultaneous Immersion Mirau Interferometry (SIMI), which facilitates simultaneous acquisition of all interferograms and eliminates the effects of vibration. Polarization optics, incorporated into the design, introduces a phase delay to one of the components of the test beam. This enables simultaneous creation and spatial separation of two interferograms, which are combined with the background image to reconstruct the intensity map of the specimen. Our results of imaging live and fixed cells with IMI and SIMI show that this system produces images of a quality that is sufficient to perform targeted cellular irradiation experiments.


A CXCR4-dependent chemorepellent signal contributes to the emigration of mature single-positive CD4 cells from the fetal thymus.
Developing thymocytes undergo maturation while migrating through the thymus and ultimately emigrate from the organ to populate peripheral lymphoid tissues. The process of thymic emigration is controlled in part via receptor-ligand interactions between the chemokine stromal-derived factor (SDF)-1, and its cognate receptor CXCR4, and sphingosine 1-phosphate (S1P) and its receptor S1PR. The precise mechanism by which S1P/S1PR and CXCR4/SDF-1 contribute to thymic emigration remains unclear. We proposed that S1P-dependent and -independent mechanisms might coexist and involve both S1P-induced chemoattraction and SDF-1-mediated chemorepulsion or fugetaxis of mature thymocytes. We examined thymocyte emigration in thymi from CXCR4-deficient C57BL/6 embryos in a modified assay, which allows the collection of CD62L(high) and CD69(low) recent thymic emigrants. We demonstrated that single-positive (SP) CD4 thymocytes, with the characteristics of recent thymic emigrants, failed to move away from CXCR4-deficient fetal thymus in vitro. We found that the defect in SP CD4 cell emigration that occurred in the absence of CXCR4 signaling was only partially overcome by the addition of the extrathymic chemoattractant S1P and was not associated with abnormalities in thymocyte maturation and proliferative capacity or integrin expression. Blockade of the CXCR4 receptor in normal thymocytes by AMD3100 led to the retention of mature T cells in the thymus in vitro and in vivo. The addition of extrathymic SDF-1 inhibited emigration of wild-type SP cells out of the thymus by nullifying the chemokine gradient. SDF-1 was also shown to elicit a CXCR4-dependent chemorepellent response from fetal SP thymocytes. These novel findings support the thesis that the CXCR4-mediated chemorepellent activity of intrathymic SDF-1 contributes to SP thymocyte egress from the fetal thymus.


Hypofrontality and negative symptoms in major depressive disorder.
The purpose of the current study was to compare regional cerebral blood flow (rCBF) in patients with major depressive disorder (MDD) to that of healthy subjects and to examine the relationship between rCBF, depressive symptoms (DS) and negative symptoms (NS) in these patients. Eleven psychiatric inpatients with diagnosed (MDD) and 15 normal control subjects were administered the scale for the assessment of negative symptoms (SANS) and the modified Hamilton rating scale for depression with items descriptive of NS excluded (HRSD-DS). Each patient underwent a SPECT scan using 99mTc-HMPAO at rest. Cortical and subcortical regions of interest (ROIs) were symmetrically defined in each hemisphere. Cortical-to-cerebellar perfusion ratios were established quantitatively using ADAC software. Subjects in the MDD group had significantly lower rCBF in the frontal cortex and cinglulate gyrus (MANOVA, p = 0.038) due to differences in dorsolateral prefrontal cortex bilaterally (right F = 7.69, p = 0.01; left F = 8.41, p = 0.01) in the right orbitofrontal cortex (F = 6.79, p = 0.02) and in the cingulate gyrus (F = 5.34, p = 0.03). The MDD group also had lower rCBF in the posterior cortical structures (MANOVA, p = 0.072), which was due to decreased perfusion in the right parietal cortex (F = 7.54, p = 0.01). There were negative correlations between the SANS total score and rCBF in both the left dorsolateral prefrontal cortex (Pearson's correlation coefficient r = .-67, p < 0.05) and the left anterior temporal cortex (r = -0.71, p < 0.01) in MDD patients. Additionally, there were positive correlations between HRSD scores and rCBF in the left anterior temporal (r = 0.71, p < 0.01), left dorsolateral prefrontal (r = 0.70, p < 0.01), right frontal (r = 0.82, p < 0.01) and right posterior temporal (r = 0.74, p < 0.01) cortices. Cerebral blood flow was not correlated with either mini-mental state examination scores or age. This preliminary study replicates the finding of hypofrontality in MDD and indicates that decreased perfusion is associated specifically with negative symptom severity. These results support the hypothesis that, in MDD, negative symptoms and symptoms of depression are distinct phenomena and underscore the importance of negative symptom evaluation in neuroimaging studies of MDD and other disorders.


Design of retroviral vectors for the insertion of foreign deoxyribonucleic acid sequences into the avian germ line.
Because the available avian leukosis viral (ALV) vectors are moderately oncogenic in vivo, they are not suitable for insertion into the germ line. A significant reduction in the oncogenicity of the ALV vectors can be achieved by substituting the noncoding long terminal repeats (LTR) regions of the ALV virus with the LTR of the nononcogenic endogenous RAV-O virus. There is good evidence that the resulting RAV-O LTR vectors can be inserted into the germ line of domestic chickens and have the potential for inserting cloned sequences that can be used for poultry improvement.


A traumatic deterioration in general surgeons access to emergency theatre.
An audit has been carried out of general surgical emergency theatre usage before and after the allocation of some of the emergency theatre time for trauma lists. The median delay between decision to operate and operation starting rose from 1 hour 15 minutes to 2 hours 30 minutes. There was a fall in the number of operations carried out during the day (p < 0.001) and a corresponding increase in the number of procedures performed after midnight (p < 0.005). Emergency theatre usage provides advantages to patient and surgeon alike. However, by its nature it will not be fully occupied all of the time. There is always likely to be a temptation to use some of the "free time' for non-emergency cases. This results in the advantages of the emergency theatre being lost.


Herpes simplex virus: recurrent and nonrecurrent strains.
A study of three Herpes Simplex strains with different frequencies of recurrent disease was done using the New Zealand white rabbit eye model. Each of the three strains, the McKrae strain (high frequency), the E-43 strain (low, frequency), and the CGA-3 (no recurrence) grew well in the rabbit corneal epithelium and produced overt recognizable disease for up to 5 days post-infection, thus minimizing differences in virus reactivation due to a lack of or insufficient ganglionic colonization. Asymptomatic shedding and spontaneous recurrences, as well as iontophoretically induced recurrences, were seen in the E-43 and McKrae strains, but not in the CGA-3-infected animals. The virus strain's optimum temperature was an important aspect of its reactivation process, as shown by the failure of the nonrecurrent CGA-3 to replicate at the host's core temperature (39 degrees C). The fact that these explants yielded infectious virus at 33 degrees C and not at 39 degrees C confirmed that the CGA-3 had colonized the ganglia, and its lack of recurrences or shedding suggests a temperature-dependency relationship. Our observations were further supported by the preferential growth at 39 degrees C of fresh clinical isolates obtained from HSV encephalitis and herpes labialis. Isolates from animals infected with the heterogeneous McKrae were classified as shedders (isolated in the absence of disease) and recurrent (isolated from a recurrent lesion). Both shedders and recurrent isolates were of a homologous nature and retained their phenotype when tested. From this study, we theorize that reactivation and disease may have different regulatory mechanisms. The type of recurrent disease (lesions, asymptomatic shedding, or none) is virus-dependent and frequency of disease may be regulated by host functions.


Phenolic composition and inhibitory effect against oxidative DNA damage of cooked cowpeas as affected by simulated in vitro gastrointestinal digestion.
Cowpeas contain phenolic compounds with potential health benefits. The effect of simulated gastrointestinal digestion on phenolic composition of cooked cowpeas and the ability of the digests to inhibit radical-induced DNA damage was determined. A red and a cream-coloured cowpea type were used. The phenolic composition of acetone extracts and enzyme digests of cooked cowpeas was determined using UPLC-MS. Compounds such as p-hydroxybenzoic acid, p-coumaric acid, coumaroylaldaric acid and feruloylaldaric acid were present in the acetone extracts of the cooked cowpeas but were not detected in the enzyme digests. Glycosides of quercetin and myricetin decreased upon in vitro gastrointestinal digestion of cooked cowpeas whereas flavan-3-ols were hardly present except catechin glucoside. The enzyme digest of the red cowpea type was about thrice as effective as that of the cream cowpea type in protecting DNA from oxidative damage. The observation that enzyme digests of cooked cowpeas inhibited radical-induced DNA damage suggests that cowpea phenolics retain some radical scavenging activity after gastrointestinal digestion.


Improvement of aerobic treatment process by cross-linked polyvinylpyridine.
In continuous aerobic treatment of artificial sewage by activated sludge, the rate of removal of chemical oxygen demand (COD) was markedly enhanced by the presence of cross-linked poly-4-vinylpyridine (PVP). The concentration of dissolved oxygen (DO) was also low in the presence of PVP. The extent of improvement in COD removal increased with increases in substrate load and the surface area of the PVP in the working space of the test apparatus. These results suggest an increase of the bacterial population resulting from the presence of the PVP. However, formation of measurable biofilm was not detected on the surface of the PVP during continuous aerobic treatment.


Met provides essential signals for liver regeneration.
Genetic analysis in mice has demonstrated a crucial role of the Met tyrosine kinase receptor and its ligand, hepatocyte growth factor/scatter factor (HGF/SF), in development of the liver, muscle, and placenta. Here, we use conditional mutagenesis in mice to analyze the function of Met during liver regeneration, using the Mx-cre transgene to introduce the mutation in the adult. After partial hepatectomy in mice carrying the Mx-cre-induced Met mutation, regeneration of the liver is impaired. Comparison of signal transduction pathways in control and mutant livers indicates that Met and other signaling receptors cooperate to fully activate particular signaling molecules, for instance, the protein kinase Akt. However, activation of the Erk1/2 kinase during liver regeneration depends exclusively on Met. Signaling crosstalk is thus an important aspect of the regulation of liver regeneration. Analysis of cell cycle progression of hepatocytes in conditional Met mutant mice indicates a defective exit from quiescence and diminished entry into S phase. Impaired liver regeneration is accompanied by compensatory physiological responses that include prolonged up-regulation of HGF/SF and IL-6 in peripheral blood. Our data demonstrate that the HGF/SF/Met signaling system is essential not only during liver development but also for the regeneration of the organ in the adult.


Ghrelin and des-acyl ghrelin promote differentiation and fusion of C2C12 skeletal muscle cells.
Ghrelin is an acylated peptidyl gastric hormone acting on the pituitary and hypothalamus to stimulate appetite, adiposity, and growth hormone release, through activation of growth hormone secretagogue receptor (GHSR)-1a receptor. Moreover, ghrelin features several activities such as inhibition of apoptosis, regulation of differentiation, and stimulation or inhibition of proliferation of several cell types. Ghrelin acylation is absolutely required for both GHSR-1a binding and its central endocrine activities. However, the unacylated ghrelin form, des-acyl ghrelin, which does not bind GHSR-1a and is devoid of any endocrine activity, is far more abundant than ghrelin in plasma, and it shares with ghrelin some of its cellular activities. In here we show that both ghrelin and des-acyl ghrelin stimulate proliferating C2C12 skeletal myoblasts to differentiate and to fuse into multinucleated myotubes in vitro through activation of p38. Consistently, both ghrelin and des-acyl ghrelin inhibit C2C12 proliferation in growth medium. Moreover, the ectopic expression of ghrelin in C2C12 enhances differentiation and fusion of these myoblasts in differentiation medium. Finally, we show that C2C12 cells do not express GHSR-1a, but they do contain a common high-affinity binding site recognized by both acylated and des-acylated ghrelin, suggesting that the described activities on C2C12 are likely mediated by this novel, yet unidentified receptor for both ghrelin forms.


Advanced access works! Improved patient satisfaction, access, and P4P scores.
Practices continue to struggle with patient scheduling and assuring access to care for their patients. Consequently, practices are seeking new, innovative ways to redesign practice operations to improve patient, physician, and staff satisfaction. One of the foundations of this redesign is Advanced Access. Advanced Access is a system that gives patients the ability to schedule an appointment with their physician when they want or need to be seen. It redesigns patient access and the scheduling process to increase patient throughput and the medical practice's capacity. This article describes the tenets and implementation process Advanced Access and addresses the challenges that practices face as they implement Advanced Access.


Different study criteria affect the prevalence of benzodiazepine use.
Different prevalences of benzodiazepine (BZ) use are described in the literature. The present study assessed the effects of employing various definitions of BZ use and various observation periods on the prevalence rate of BZ use in an open population aged 18-74 years. In a literature review, prevalence studies were systematically compared. In a second stage, a descriptive cross-sectional multipractice study was analysed using 48,046 prescriptions of BZ in the past year given to a population of 80,315 patients at 31 general practices in the Nijmegen Health Area. From this database, prevalence rates were calculated applying different definitions of BZ use and different observation periods. In the literature, prevalence rates varied between 2.2 and 17.6%. There was wide variation in definitions of BZ use and observation period. In our prescription database, depending on the definitions of BZ use and observation period, prevalence rates ranged from 0.2% to 8.9%. The ratio of female:male (2:1) remained constant irrespective of the prevalence rate. Age distribution varied according to the duration of use: among long-term BZ users, approximately 80% were older than 45 years; among short-term BZ users, approximately 55% were older than 45 years. The wide variation in prevalence rates of BZ use reported in the literature can largely be explained by differences in definitions of BZ use and observation period. This affected the distribution of some BZ-use-related variables such as age. For reliable comparisons of BZ use, standardisation of the definition of BZ use is required. A proposal for standardising methodology is presented.


Three monoclonal immunoglobulins, an IgG2(kappa), an IgM(kappa) and an IgM/A hybrid, in one patient. II. Sharing of common variable regions.
Amino acid sequencing and haemagglutination inhibition studies were performed on three monoclonal immunoglobulins (an IgG2, an IgM and an IgM/A hybrid) isolated from a patient afflicted with a multiple gammopathy. The results demonstrated that all three proteins have shared idiotypic determinant(s). Furthermore, the light chains of all three paraproteins have identical NH2-terminal amino-acid sequences at all positions determined thus far. Similarly, the NH2-terminal amino-acid sequence of the gamma 2 chains is identical to that of the mu chain. The evidence strongly suggests a common ancestral clonal origin for cells which produce these paraproteins and that identical variable region (VH and VL) genes were used by the ESM lymphocyte subclones in the biosynthesis of the respective IgM, IgG, and IgM/A hybrid molecules. The occurrence of a mu/alpha hybrid chain, which shares identical V regions with a mu and a gamma chain, is consistent with the concept that IgM-producing cells can develop directly into cells producing other classes of immunoglobulins via separate pathways during B-cell maturation.


Learning curve for endorectal ultrasound in young and elderly: lights and shades.
Aim of the study is to highlight difficulties faced by an inexperienced surgeon in approaching endorectal-ultrasound, trying to define when learning curve can be considered complete. A prospective analysis was conducted on endorectal-ultrasound performed for subperitoneal rectal adenocarcinoma staging in the period from January 2008 to July 2013, reported by a single surgeon of Department of Oncology, Section of General Surgery, "San Luigi Gonzaga" Teaching Hospital, Orbassano (Turin, Italy); the surgeon had no previous experience in endorectal-ultrasound. Fourty-six endorectal-ultrasounds were divided into two groups: early group (composed by 23 endorectal-ultrasounds, made from January 2008 to May 2009) and late group (composed by 23 endorectal-ultrasound, carried out from June 2009 to July 2013). In our experience, the importance of a learning curve is evident for T staging, but no statystical significance is reached for results deal with N stage. We can conclude that ultrasound evaluation of anorectal and perirectal tissues is technically challenging and requires a long learning curve. Our learning curve can not be closed down, at least for N parameter.


Immunocytochemical localization of luteinizing hormone-releasing hormone (LHRH) in Vibratome-sectioned brain.
Immunocytochemical localization of neuropeptides such as luteinizing hormone-releasing hormone (LHRH) is generally performed on Bouin's fixed tissue sections, following tissue dehydration in alcohols and embedment in paraffin. When the final reaction product accurately reflects content and distribution of the neuropeptide has not been examined carefully. Our data indicate a decrease in radioimmunoassayable LHRH content of brain fixed in Bouin's solution and a further significant reduction following dehydration with alcohol. In order to circumvent this loss of hormone, sections of fixed brain were cut on a Vibratome at 30 micron and collected in phosphate-saline buffer. These Vibratome sections revealed a significantly greater amount of overall immunoreactivity and fiber distribution as compared to paraffin-embedded sectioned tissue. These results suggest that certain neuropeptides, soluble in alcohol, can be extracted during dehydration processes necessary for paraffin embedment.


Satisfaction, Intimacy and Conflict in Canadian Couples: An Analysis of Change from Adolescence to Adulthood.
Romantic relationship qualities are likely to change from adolescence to adulthood. Therefore, we undertook a longitudinal study to examine changes in satisfaction, intimacy, and conflict over this period by simultaneously testing the effects of age, relationship length, and their interaction. These qualities were measured at nine-time points from ages 16 to 30 in a Canadian sample of 337 participants (62.9% women) who reported being in a romantic relationship at least once over this period. The results of multilevel analyses show that satisfaction, intimacy, and conflict decline with age but increase with relationship length. Moreover, age and relationship length were found to have a significant interactive effect on satisfaction and intimacy.


Improvements in histological techniques for epoxy-resin embedded bone specimens.
A procedure is presented in which some of the processing difficulties with fixation, embedding and cutting whole mouse bones and large bone pieces from other species are considered. The bone specimens are fixed in acetone or by a Karnovsky-formol-saline process which preserves intact endosteal surface-to-cortex layers. After fixation the bones are embedded in a hard mixture of epoxy resin to provide blocks with face sizes up to 3.5 x 3.0 cm. Mineralized sections are cut to 4 micrometer; demineralized at 3 micrometer. Sections are fastened to gelatin-subbed slides with pressure plates which produce flat, secure sections. After removal of the plastic, an unmodified Mayer's hematoxylin and a polychromatic eosin staining method is applied to demineralized sections, and a slightly modified method to mineralized sections.


Identifying the causes, prevention and management of crises in dementia. An online survey of stakeholders.
Crisis situations in dementia can lead to hospital admission or institutionalisation. Offering immediate interventions may help avoid admission, whilst stabilising measures can help prevent future crises. Our objective was to identify the main causes of crisis and interventions to treat or prevent crisis in persons with dementia based on different stakeholder perspectives. An online questionnaire was developed to identify the causes of crisis and appropriate interventions in a crisis. Participants included people with dementia, family carers and staff working in health and social care, including emergency and voluntary sectors, and academia. The results ranked the main causes of crisis, interventions that can prevent a crisis and interventions that can be useful in a crisis. Wandering, falls and infection were highly rated as risk factors for crises across all stakeholder groups. Consumers rated aggression as less important but severity of memory impairment as much more important than the other groups did. Education and support for family carers and home care staff were highly valued for preventing crises. Well-trained home care staff, communication equipment, emergency contacts and access to respite were highly valued for managing crises. We identified triggers and interventions that different stakeholders see as important for crisis in dementia. Recognition of these may be critical to planning effective and accepted support and care for people with dementia.


[Detection of circulating anticellular antibodies by indirect immunofluorescence on HEp-2 cell substrates: study of the clinical value of rare fluorescence patterns].
We detected anticellular antibodies (Ab) in 867 sera from patients with inflammatory rheumatic disorders by indirect immunofluorescence technique on HEp-2 cells and searched for clinically relevance of the rare fluorescence staining pattern (n = 133). We could find associations of 1. spekled nuclear pattern and Ab to U1-nRNP and La, 2. nucleolar pattern and scleroderma, 3. peripheral nuclear membrane pattern, Ab to dsDNA and SLE, 4. centromere staining and CRST syndrome, 5. intermediär filament pattern and permanent cellular destructions in erosive arthritis, 6. mitochondrial staining and inflammatory hepatic disorders. The anticellular Ab staining patterns on HEp-2 cells might be precious additionally markers for diagnosis and prognosis of inflammatory rheumatic diseases.


Depressive symptoms and their social contexts: a qualitative systematic literature review of contextual interventions.
Numerous observational studies demonstrate associations between social context and depressive symptoms, yet few intervention trials exist in this arena. This review examines intervention trials that explore the impact of contextual change on depressive symptoms. Electronic literature databases of PubMed and PsycINFO, bibliographies of retrieved articles and the publicly available internet were searched for English-language articles published between 1997 and 2008. Peer-reviewed studies were eligible for inclusion if they reported contextual interventions and depressive symptoms measures in adult populations without other significant underlying medical or psychological illness. In total, 2,128 studies met search term criteria. Of these, 13 studies meeting inclusion criteria were classified by type of intervention. Qualitative synthesis was used to interpret the mental health impact of contextual interventions. The interventions focused on employment, housing, poverty, parenting and violence. Eight of these studies reported a decrease in depressive symptoms and/or psychological distress in intervention groups. Interventions varied in focus, length of follow-up and measures of depressive symptoms. Contextual interventions for the prevention and treatment of depressive symptoms and psychological distress can be effective, though very limited data exist in this field. Policy implications include a greater emphasis on improving context to decrease depression and other mental disorders.


Molecular Targets of Aptamers in Gastrointestinal Cancers: Cancer Detection, Therapeutic Applications, and Associated Mechanisms.
Gastrointestinal (GI) cancers are among the most common cancers that impact the global population, with high mortality and low survival rates after breast and lung cancers. Identifying useful molecular targets in GI cancers are crucial for improving diagnosis, prognosis, and treatment outcomes, however, limited by poor targeting and drug delivery system. Aptamers are often utilized in the field of biomarkers identification, targeting, and as a drug/inhibitor delivery cargo. Their natural and chemically modifiable binding capability, high affinity, and specificity are favored over antibodies and potential early diagnostic imaging and drug delivery applications. Studies have demonstrated the use of different aptamers as drug delivery agents and early molecular diagnostic and detection probes for treating cancers. This review aims to first describe aptamers' generation, characteristics, and classifications, also providing insights into their recent applications in the diagnosis and medical imaging, prognosis, and anticancer drug delivery system of GI cancers. Besides, it mainly discussed the relevant molecular targets and associated molecular mechanisms involved, as well as their applications for potential treatments for GI cancers. In addition, the current applications of aptamers in a clinical setting to treat GI cancers are deciphered. In conclusion, aptamers are multifunctional molecules that could be effectively used as an anticancer agent or drug delivery system for treating GI cancers and deserve further investigations for clinical applications.


Quantum coherence of image-potential states.
The quantum dynamics of the two-dimensional image-potential states in front of the Cu(100) surface is measured by scanning tunneling microscopy and spectroscopy. The dispersion relation and the momentum resolved phase-relaxation time of the first image-potential state are determined from the quantum interference patterns in the local density of states at step edges. It is demonstrated that the tip-induced Stark shift does not affect the motion of the electrons parallel to the surface.


Power Doppler analysis of tendon vascularization.
Forty-nine patients with tendonitis (patellar in 16, quadriceps in two, Achilles in 12, rotator cuff disease in 19) and 47 patients with tenosynovitis (acute tenosynovitis in 25, stenosing tenosynovitis in 22) underwent ultrasound (US) and Power Doppler (PD)-US examination. Spectral analysis of flow signals was performed in all patients. Ten patients (six with tendonitis, four with tenosynovitis) were rewired after medical therapy. Six healthy volunteers were also examined for control purposes. Three different patterns of flow distribution were found in patients with tendonitis and active tenosynovitis. The vessels of tendons without tendon sheaths began with great peduncles at the level of the peritendinous soft tissues and were then distributed inside the tendon (pattern I). A clear peritendinous hypervascular pattern was found in all active tenosynovitis, but no vessels were found inside the tendons (pattern II). In some cases of intratendinous or partial lesions PD-US revealed some vessels located near or inside the lesion (pattern II). On spectral analysis these vessels corresponded to arteries with a low resistance index or small venules. PD-US revealed a significant reduction of flow signals in patients rewired after medical therapy. No pathological flow signals were found either in patients with stenosing tenosynovitis or in the control group. PD-US gives us an in vivo confirmation of tendon vascularity. Spectral analysis adds further information to gray-scale US.


Correlation between incident and emission polarization in nanowire surface plasmon waveguides.
Nanowire plasmons can be launched by illumination at one terminus of the nanowire and emission can be detected at the other end of the wire. Using polarization dependent dark-field scattering spectroscopy, we measure how the polarization of the emitted light depends on the polarization of the incident light. We observe that the shape of the nanowire termination plays an important role in determining this polarization change. Depending on termination shape, a nanowire can serve as either a polarization-maintaining waveguide, or as a polarization-rotating, nanoscale half-wave plate. The understanding of how plasmonic waveguiding influence the polarization of the guided light is important for optimizing the structure of integrated plasmonic devices.


Issues in the development of language intervention programmes.
An attempt has been made in this paper to address some issues involved in the development of language intervention programmes. The relative neglect of 'language' in the paper is justified by the importance of more general issues. After cursory attention to prescriptiveness in programmes, the concentration has been on the 'training of the trainers' and the need for an adequate and effective instructional model. Particular attention is given to evaluation and the need for a design which while acknowledging the practicalities of life in the field can nevertheless assist in determining the effects of the intervention (with a nod in the direction of casting the net sufficiently wide to encompass possible unintended effects). Finally, there is discussion of implementation, covering guidelines to bear in mind the developing the intervention and stressing that without successful implementation even the most effective programme fails, as it disappears like water in to the sands of the desert.


Transglycosylated Starch Improves Insulin Response and Alters Lipid and Amino Acid Metabolome in a Growing Pig Model.
Due to the functional properties and physiological effects often associated with chemically modified starches, significant interest lies in their development for incorporation in processed foods. This study investigated the effect of transglycosylated cornstarch (TGS) on blood glucose, insulin, and serum metabolome in the pre- and postprandial phase in growing pigs. Eight jugular vein-catheterized barrows were fed two diets containing 72% purified starch (waxy cornstarch (CON) or TGS). A meal tolerance test (MTT) was performed with serial blood sampling for glucose, insulin, lipids, and metabolome profiling. TGS-fed pigs had reduced postprandial insulin (p < 0.05) and glucose (p < 0.10) peaks compared to CON-fed pigs. The MTT showed increased (p < 0.05) serum urea with TGS-fed pigs compared to CON, indicative of increased protein catabolism. Metabolome profiling showed reduced (p < 0.05) amino acids such as alanine and glutamine with TGS, suggesting increased gluconeogenesis compared to CON, probably due to a reduction in available glucose. Of all metabolites affected by dietary treatment, alkyl-acyl-phosphatidylcholines and sphingomyelins were generally increased (p < 0.05) preprandially, whereas diacyl-phosphatidylcholines and lysophosphatidylcholines were decreased (p < 0.05) postprandially in TGS-fed pigs compared to CON. In conclusion, TGS led to changes in postprandial insulin and glucose metabolism, which may have caused the alterations in serum amino acid and phospholipid metabolome profiles.


[Characteristics of soil seed banks in backwater area of Three Gorges Reservoir water-level-fluctuating zone at initial stage of river-flooding].
A germination test was made to study the characteristics of soil seed banks in the backwater area (including the flooded, non-flooded, and control areas of secondary bush and abandoned farmland) of Three Gorges Reservoir water-level-fluctuating zone. There existed significant differences in the soil seed banks between secondary bush and abandoned farmland, with an average seed density being 6991 +/- 954 seed per m2 and 26193 +/- 6928 seed per m2, respectively. Flooded area had the lowest seed density, while non-flooded area had the highest one. The seed density decreased with soil depth. A total of 118 species belonging to 45 families and 97 genera were detected in the soil seed banks of secondary bush and abandoned farmland, most of which were annual and perennial herbage species, belonging to Asteraceae, Poaceae, Scrophulariaceae, and Cruciferae. Among the 118 species, there were 34 species (occupying 28.8%) whose individuals accounted for less than 0.01% of the total. In the soil seed banks of secondary bush and abandoned farmland, the species number was similar, species diversity index and evenness index were relatively high, but the dominant species differed greatly, and the ecological dominance was relatively low. The species diversity in non-flooded area and the ecological dominance in flooded area were the highest, and the similarity index between the flooded and non-flooded areas was the highest.


Geometrical accuracy and fusion of multimodal vascular images: a phantom study.
The aim of this work was to compare the geometrical accuracy of x-ray angiography, magnetic resonance imaging (MRI), x-ray computed tomography (XCT), and ultrasound imaging (B-mode and IVUS, or intravascular ultrasound) for measuring the lumen diameters of blood vessels. An image fusion method was also developed to improve these measurements. The images were acquired from a phantom that mimic vessels of known diameters. After acquisition, the multimodal images were coregistered by manual alignment of fiducial markers, and then by maximization of mutual information. The fusion method was performed by means of a fuzzy logic modeling approach followed by a combination process based on a possibilistic theory. The results showed (i) the better geometrical accuracy of XCT and IVUS compared to the other modalities, and (ii) the better accuracy and smaller variability of fused images compared to single modalities, with respect to most diameters investigated. For XCT, the error varied from 0.4% to 5.4%, depending on the vessel diameter that ranged from 0.93 to 6.24 mm. For IVUS, the error ranged from -0.3% to 1.7% but the smallest vessel (0.93 mm) could not be investigated because of the probe size. Compared to others fusion schemes, the XCT-MRI fused images provided the best results for both accuracy (from -1.6% to 0.2% for the three largest vessels) and robustness (mean relative error of 1.9%). To conclude, this work underlined both the usefulness of the multimodality vascular phantom as a validation tool and the utility of image fusion in the vascular context.


Efficient enantioselective synthesis of 3-aminochroman derivatives through ruthenium-Synphos catalyzed asymmetric hydrogenation.
A highly enantioselective asymmetric hydrogenation of various trisubstituted enamides derived from chroman-3-ones promoted by cationic Ru-Synphos catalysts is reported. This atom-economical and clean method provides an efficient route to optically active 3-aminochroman derivatives, which are important pharmacophores found in numerous drug candidates, in high chemical yields and enantiomeric excesses up to 96%.


[Evidence-based Chinese medicine:theory and practice].
The introduction and popularization of evidence-based medicine has opened up a new research field of clinical efficacy evaluation of traditional Chinese medicine(TCM), produced new research ideas and methods, and promoted the progress of clinical research of TCM. After about 20 years assiduous study and earnest practice, the evidence based evaluation method and technique, which conforms to the characteristics of TCM theory and practice, has been developing continuously. Evidence-based Chinese medicine (EBCM) has gradually formed and become an important branch of evidence-based medicine. The basic concept of evidence-based Chinese medicine: EBCM is an applied discipline, following the theory and methodology of evidence-based medicine, to collect, evaluate, produce, transform the evidence of effectiveness, safety and economy of TCM, to reveal the feature and regular pattern of TCM taking effect, and to guide the development of clinical guidelines, clinical pathways and health decisions. The effects and achievements of EBCM development: secondary studies mainly based on systematic review/Meta-analysis were extensively carried out; clinical efficacy studies mainly relying on randomized controlled trials grew rapidly; clinical safety evaluations based on real world study have been conducted; methodological researches mainly focused on study quality control deepened gradually; internationalization researches mainly on report specifications have got some breakthroughs; standardization researches based on treatment specification were strengthened gradually; the research team and talents with the characteristics of inter-disciplinary have been steadily increased. A number of high-quality research findings have been published at international well-known journals; the clinical efficacy and safety evidence of TCM has been increased; the level of clinical rational use of TCM has been improved; a large number of Chinese patent medicines with big market have been cultured. The future missions of EBCM mainly consist of four categories (scientific research, methodology and standard, platform construction and personnel training) with nine tasks. ①Carry out systematic reviews to systematically collect clinical trial reports of TCM and establish database of clinical evidence of TCM; ②Carry out evidence transformation research to lay the foundation for the development of clinical diagnosis and treatment guidelines, clinical pathways of TCM, and for the screening of basic drug list and medical insurance list, and for the policy-making relevant to TCM; ③Conduct researches to evaluate the advantages and effective regular patterns of TCM and form the evidence chain of TCM efficacy; ④Carry out researches for the safety evaluation of TCM, and provide evidence supporting the rational and safe use of TCM in clinical practice; ⑤Conduct researches on methodology of EBCM and provide method for developing high quality evidence; ⑥Carry out researches to develop standards and norms of TCM, and to form methods, standards, specifications and technical systems; ⑦Establish data management platform for evidence-based evaluation of TCM, and promote data sharing; ⑧Build international academic exchange platform to promote international cooperation and mutual recognition of EBCM research; ⑨Carry out education and popularization activities of evidence-based evaluation methods, and train undergraduate students, graduate students, clinical healthcare providers and practitioners of TCM. The development of EBCM, as it was, not only promoted the transformation of clinical research and decision-making mode of TCM, contributed to the modernization and internationalization of TCM, but also enriched the connotation of Evidence-based Medicine.


What is new in tics, dystonia and chorea?
Movement disorders comprise hyperkinetic involuntary movements (eg tremor, myoclonus, tics, dystonia and chorea) and hypokinetic (parkinsonism) disorders. Tics are cardinal features of primary tic disorders encompassing Tourette syndrome (TS), but are also found in some neurodegenerative conditions and may be induced by psychoactive substances. The first line treatment for tics is pharmacological (mainly dopamine receptor blockers or alpha-2 adrenergic agonists) and behavioural. Dystonia and chorea syndromes are considerably heterogeneous in aetiology, and age at onset, body distribution of the movement disorder, accompanying neurological motor and non-motor features, and systemic manifestations are all important to reach a correct aetiological diagnosis. While symptomatic pharmacological treatment remains the mainstay of treatment for choreas, deep brain stimulation surgery has a well-defined place in the management of medically refractory dystonia.


ACOG Committee Opinion No. 359: commercial enterprises in medical practice.
Increasing numbers of physicians sell and promote both medical and nonmedical products as part of their practices. Physicians always have rendered advice and treatment for a fee, and this practice is appropriate. It is unethical under most circumstances, however, for physicians to sell or promote medical or nonmedical products or services for their financial benefit. The following activities are considered unethical: sale of prescription drugs to be used at home, sale or promotion of nonprescription medicine, sale or promotion of presumptively therapeutic agents that generally are not accepted as part of standard medical practice, sale or promotion of non-health-related items, recruitment of patients or other health care professionals into multilevel marketing arrangements, and sale or promotion of any product in whose sale the physician has a significant financial interest. It is ethical and appropriate, however, to sell products to patients as follows: sale of devices or drugs that require professional administration in the office setting; sale of therapeutic agents, when no other facilities can provide them at reasonable convenience and at reasonable cost; sale of products that clearly are external to the patient-physician relationship, when such a sale would be considered appropriate in an external relationship; and sale of low-cost products for the benefit of community organizations. A rationale is provided for both the prohibited activities and exceptions.


Characteristics of readmitted psychiatric inpatients.
This study examined sociodemographic, diagnostic, psychological, and episode-based variables in a sample of 130 psychiatric patients admitted to treatment at least twice in a 6-yr. period. Short length of initial hospitalization (r = -.30, p < .01) and younger age on initial admission (r = -.20, p < .05) were significantly correlated with frequent hospital admissions. Scores on four of the subscales of the WAIS-R were significantly correlated with readmission, confirming that patients who have fewer cognitive resources are at risk of frequent admissions. A multiple regression analysis combining variables to predict readmission accounted for only 12% of the common variance (r128 = .34, p < .01), however, indicating that a prediction equation with these variables has limited clinical utility.


Finite-element approach to Brownian dynamics of polymers.
In the last decades simulation tools for Brownian dynamics of polymers have attracted more and more interest. Such simulation tools have been applied to a large variety of problems and accelerated the scientific progress significantly. However, the currently most frequently used explicit bead models exhibit severe limitations, especially with respect to time step size, the necessity of artificial constraints and the lack of a sound mathematical foundation. Here we present a framework for simulations of Brownian polymer dynamics based on the finite-element method. This approach allows simulating a wide range of physical phenomena at a highly attractive computational cost on the basis of a far-developed mathematical background.


Evolution of Atlantic Meridional Overturning Circulation since the last glaciation: model simulations and relevance to present and future.
The Atlantic Meridional Overturning Circulation (AMOC) and the associated water masses have changed dramatically during the glacial-interglacial cycle. Here, I review some recent progress in the modelling of the AMOC and water masses since the Last Glacial Maximum and discuss the relevance of these past AMOC studies to the present and future AMOC study. Recent studies suggested that Atlantic water masses were constrained by carbon isotopes (δ13C) and neodymium isotopes (εNd), while the strength of the AMOC better was constrained by protactinium/thorium ratio (231Pa/230Th) and the spatial gradient of calcite oxygen isotopes (δ18Oc). In spite of the shallower AMOC at the glacial period, its intensity did not differ substantially from the present because of the cancellation of opposite responses to the rising CO2 and the retreating ice sheet. This article is part of a discussion meeting issue 'Atlantic overturning: new observations and challenges'.


[Situation analysis for drug clinical trial institutions].
Drug clinical trial is an important link in the chain of new drug research and development. The results of drug discovery and development directly depend on the extent of standardization of clinical trials. Therefore, improving the quality of drug clinical trials is of great importance, and drug clinical trial institutions play a crucial role in the quality management of drug clinical trials. After years of development, the overall level of drug clinical trials has advanced rapidly in China, and a large number of clinical trials of traditional Chinese medicine have also been carried out. However, there is still a big gap between our country and developed countries. Therefore, for the construction and management of Chinese drug clinical trial institutions, there is still a long way to go. This study aims to analyze the current development of drug clinical trial institutions in China and explore the existing problems from three aspects, including current situations of institutional organization and management, regional and professional distributions, and quality control. And some suggestions are put forward finally, including support of traditional Chinese medicine, introduction of drug-risk management system, and construction of information management.


Use of frequency-shifted/time-compressed speech with hearing-impaired children.
Several electromechanical aids to education for hearing-impaired children have been studied. One method that has received minimal attention is that of frequency-shifted/time-compressed (FS/TC) speech. This study was designed to determine if intelligibility scores on a standard intelligibility measure for children, whereby the words on the test was modified by 35% FS/TC, would show improvement from a pre- to a post-testing session. Nine hearing-impaired children were presented a 0 and 35% FS/TC speech pretest, then trained for 15 days using 35% FS/TC speech signals, and subsequently were presented a 0 and 35% FS/TC speech post-test. A second group of 9 hearing-impaired children were presented similar pre- and post-tests, but were trained under a 0% FS/TC speech condition. The group trained under the 35% FS/TC speech condition showed score gains from the pre- to post-test session, whereas the 0% FS/TC speech group showed essentially no gains from the pre- to the post-test session. The potential application of FS/TC speech to the education of hearing-impaired children were discussed.


Effects of mop handle height on shoulder muscle activity and perceived exertion during floor mopping using a figure eight method.
The aim of this study was to investigate effects of mop handle height on electromyographic (EMG) activities of the shoulder muscles and perceived exertion for the shoulder area during floor mopping using a figure eight method. An experimental study with 13 cleaners was conducted using surface EMG and category ratio (CR-10) scale. EMG activity was recorded unilaterally from the upper trapezius, infraspinatus, anterior and middle deltoid muscles. Each subject performed four trials of mopping and each trial consisted of using a different mop handle height (mop adjustment at the level of shoulder, chin, nose and eye) in randomized order. EMG data were normalized to a percentage of maximal voluntary contraction (%MVC). The muscle activities were assessed by estimating the 10th, 50th and 90th percentiles of the amplitude probability distribution function (APDF) of the EMG signals and analysed by linear mixed model analysis. Results showed that shoulder muscle activity was significantly lower when the mop handle height was adjusted to shoulder level or chin level as compared to eye level. These findings were supported by subjective ratings of exertion. It seems that mop handle height adjustment between shoulder and chin level may be recommended as a basis for figure eight mopping.


Surface Nanostructures Based on Assemblies of Polymer Brushes.
Studies on the fabrication of hierarchical surface nanostructures have significantly promoted the development of materials with new surface properties and functionalities. In this Minireview, progress on the fabrication of surface nanostructures based on surface organization of polymer brushes are outlined. In the past decades, self-assemblies of polymer brushes, including homopolymer, block-copolymer and mixed-polymer brushes, have aroused great interest in the fields of chemistry and materials science. Recent studies demonstrate that surface co-assemblies of polymer brushes and free polymer chains on solid surfaces are considered as an efficient approach to the preparation of hierarchical nanostructures. Some typical surface nanostructures and properties achieved through surface co-assembly approach are reviewed in this article. Meanwhile, the fundamental problems in the co-assembly approach are discussed and the potential applications of the hierarchical surface nanostructures are presented.


Cutaneous immunohistochemical staining pattern of p53β isoforms.
p53 is considered the guardian of the genome and as such has numerous functions. The TP53 gene is the most commonly mutated gene in cancer, and yet the exact biological significance of such mutations remains unclear. There are at least 12 different isoforms of p53, and the complexity of the p53 pathway may be in part related to these isoforms. Prior research has often not teased out what isoforms of p53 are being studied, and there is evidence in the literature that p53 isoforms are expressed differently. In this paper, we document the staining pattern of p53β isoforms in the skin and correlate it with mutational status in a subgroup of squamous proliferations of the skin. p53β isoforms are present in the cytoplasm of the differentiated layer of the epidermis and hair follicles (granular layer, infundibular and isthmus-catagen). p53β isoforms are diffusely expressed within the cytoplasm of well-differentiated squamous tumours with tetramerisation (C-terminal) domain mutations in TP53 Our results lend support to p53β isoforms being a marker of differentiation in keratinocytes.


Non-alcoholic fatty liver disease in pregnancy.
Non-alcoholic fatty liver disease (NAFLD) is now the commonest liver pathology in the UK; however, relatively little is known about its course in pregnancy or the effect it has on maternal or fetal outcomes. Described here is a 24-year-old woman in her first pregnancy who presented with non-specific symptoms and raised alanine aminotransferase with ultrasonography of her liver showing changes of steatosis and suspicious for cirrhosis, leading to a diagnosis of NAFLD. The case illustrates the need for the clinician to have awareness of this increasingly prevalent condition and for multidisciplinary management.


Comparison of post reconstruction- and reconstruction-based deep learning denoising methods in cardiac SPECT.
Objective. The quality of myocardial perfusion SPECT (MPS) images is often hampered by low count statistics. Poor image quality might hinder reporting the studies and in the worst case lead to erroneous diagnosis. Deep learning (DL)-based methods can be used to improve the quality of the low count studies. DL can be applied in several different methods, which might affect the outcome. The aim of this study was to investigate the differences between post reconstruction- and reconstruction-based denoising methods.Approach. A UNET-type network was trained using ordered subsets expectation maximization (OSEM) reconstructed MPS studies acquired with half, quarter and eighth of full-activity. The trained network was applied as a post reconstruction denoiser (OSEM+DL) and it was incorporated into a regularized reconstruction algorithm as a deep learning penalty (DLP). OSEM+DL and DLP were compared against each other and against OSEM images without DL denoising in terms of noise level, myocardium-ventricle contrast and defect detection performance with signal-to-noise ratio of a non-prewhitening matched filter (NPWMF-SNR) applied to artificial perfusion defects inserted into defect-free clinical MPS scans. Comparisons were made using half-, quarter- and eighth-activity data.Main results. OSEM+DL provided lower noise level at all activities than other methods. DLP's noise level was also always lower than matching activity OSEM's. In addition, OSEM+DL and DLP outperformed OSEM in defect detection performance, but contrary to noise level ranking DLP had higher NPWMF-SNR overall than OSEM+DL. The myocardium-ventricle contrast was highest with DLP and lowest with OSEM+DL. Both OSEM+DL and DLP offered better image quality than OSEM, but visually perfusion defects were deeper in OSEM images at low activities.Significance. Both post reconstruction- and reconstruction-based DL denoising methods have great potential for MPS. The preference between these methods is a trade-off between smoother images and better defect detection performance.


Evaluation of Two DNA Extraction Methods for Detection of Strongyloides stercoralis Infection.
Strongyloides stercoralis is present worldwide, but its prevalence is still uncertain, mainly due to the lack of sensitivity of diagnostic methods. Molecular techniques are under development, but a standardized protocol is still unavailable. We compared the sensitivity of real-time PCR, using two extraction protocols, with that of the Baermann technique. Samples were collected in the framework of the baseline screening of a randomized clinical trial evaluating moxidectin against S. stercoralis in Lao People's Democratic Republic. Two stool samples from each participant were processed by the Baermann method, and one subsample was processed by PCR. DNA was extracted using the QIAamp DNA stool minikit based on the standard protocol for the QIAamp DNA minikit (QIA) and using a modification of the QIA procedure (POL). Subsequently, all extracted samples were analyzed by real-time PCR. Overall, 95 samples were analyzed by the three diagnostic methods. Sixty-nine (72.6%) samples were positive according to the Baermann method, 25 (26.3%) by the QIA method, and 62 (65.3%) by the POL method. The sensitivities were 86% (95% confidence interval [CI], 76.7 to 92.9), 31.0% (95% CI, 21.3 to 42.6), and 78.0% (95% CI, 66.8 to 86.1) for the Baermann, QIA, and POL methods, respectively. The sensitivities calculated for each day of the Baermann method separately were 60% (48.4 to 70.8%) and 64% (52.2 to 74.2%) for days 1 and 2, respectively. In conclusion, the POL method revealed a good performance and was comparable to the Baermann test performed on two stool samples and superior to the Baermann method performed on one stool sample. Additional studies are needed to standardize a PCR protocol for S. stercoralis diagnosis.


System-Wide and Group-Specific Health Service Improvements: Cross-Sectional Survey of Outpatient Improvement Preferences and Associations with Demographic Characteristics.
Efficient patient-centred quality improvement requires an understanding of the system-wide areas of dissatisfaction along with evidence to identify the programs which can be strategically targeted according to specific patient characteristics and preferences. This cross-sectional study reports the proportion of chronic disease outpatients selecting 23 patient-centred improvement initiatives. Using univariate tests and multivariable logistic regressions, this multi-site study also identifies initiatives differentially selected by outpatients according to clinical and demographic characteristics. A total of 475 outpatients participated (49% response). Commonly selected initiatives included: reducing wait-times (22.3%); convenient appointment scheduling (16.0%); and receiving up-to-date treatment information (16.0%). Within univariate tests, preferences for information and service accessibility initiatives were not significantly associated with specific subgroups. However, seven initiatives were preferred according to age, gender, diagnosis status, and chronic disease type within multivariate models. For example, neurology outpatients were more likely to select assistance to manage psychological symptoms when compared to oncology outpatients (OR: 2.89). Study findings suggest that system-wide programs to enhance information provision are strategic approaches to improve experiences across patient characteristics. Furthermore, a few initiatives can be targeted to specific groups and emphasized the importance of detailed scoping analyses and tailored implementation plans when designing patient-centred quality improvement programs.


Correspondence on "Synergy and Antagonism between Allosteric and Active-Site Inhibitors of Abl Tyrosine Kinase".
Soellner published on the interplay between allosteric and adenosine triphosphate (ATP)-competitive inhibitors of ABL kinase, showing that the latter preferably binds to different conformational states of ABL compared to allosteric agents that specifically target the ABL myristate pocket (STAMP) and deducing that asciminib cannot bind to ABL simultaneously with ATP-competitive drugs. These results are to some extent in line with ours, although our analyses of dose-response matrices from combinations of asciminib with imatinib, nilotinib or dasatinib, show neither synergy nor antagonism, but suggest additive antiproliferative effects on BCR-ABL-dependent KCL22 cells. Furthermore, our X-ray crystallographic, solution nuclear magnetic resonance (NMR), and isothermal titration calorimetry studies show that asciminib can bind ABL concomitantly with type-1 or -2 ATP-competitive inhibitors to form ternary complexes. Concomitant binding of asciminib with imatinib, nilotinib, or dasatinib might translate to benefit some chronic myeloid leukaemia patients.


Single-Site Fe-N-C Atom Based Carbon Nanotubes for Mutually Promoted and Synergistic Oncotherapy.
A carbon nanotube (CNT) supported single-site Fe-N-C catalyst (CNTs/Fe-N-C) exhibited attractive properties in peroxidase (POD)-like activity and photothermal effect. Herein, we designed a therapeutic platform by wrapping doxorubicin (DOX) in mesoporous CNTs/Fe-N-C with the cell membrane (CM) of breast cancer. The ultimate nanoagent (CNTs/Fe-N-C/DOX/CM) exhibited high antitumor activity on account of its efficient catalytic ability, increased drug release rates, and significant photothermal effect. Due to the POD-like activity, CNTs/Fe-N-C could effectively catalyze hydrogen peroxide (H2O2) into cytotoxic hydroxyl radicals (•OH) for chemodynamic therapy (CDT) of the tumor. Besides, the released DOX not only merely induced the diagnosis of the tumor cells for chemotherapy (CT) but also generated H2O2 to promote CDT. Moreover, the photothermal effect of the nanoagent could use for photothermal therapy (PTT). The increasing temperature was conducive to the release of DOX from micropore into the cell, which indirectly enhanced CT and CDT effects. As an intelligent and multifunctional drug delivery platform, the present CNTs/Fe-N-C/DOX/CM nanoagent could be engineered with synergistic treatments and favorable biosafety, which provides a promising paradigm in site-specific antitumor treatment and biomedicine.


Mu-opioid-receptor-mediated inhibition of the N-type calcium-channel current.
The predominant consequences of mu-opioid-receptor activation are depression of both neuronal activity and transmitter release. Mu-Opioid agonists have previously been observed to increase a potassium conductance and to inhibit adenylate cyclase. We now report that activation of mu-opioid receptors directly decreases the N-type calcium-channel current in a differentiated, human neuroblastoma cell line (SH-SY5Y). The coupling between the mu-opioid receptor and the calcium channel involves a pertussis toxin-sensitive G protein and is independent of changes in adenylate cyclase activity. The inhibition of the calcium-channel current is voltage dependent because it is largely overcome by strong membrane depolarization. It is not associated with changes in the kinetics of current inactivation. Therefore, the mu-receptor belongs to the superfamily of G-protein-coupled, inhibitory neurotransmitter receptors which modulate the activity of calcium and potassium channels and adenylate cyclase.


Antibacterial agent discovery using thymidylate synthase biolibrary screening.
Thymidylate synthase (TS, ThyA) catalyzes the reductive methylation of 2'-deoxyuridine 5'-monophosphate to 2'-deoxythymidine 5'-monophosphate, an essential precursor for DNA synthesis. A specific inhibition of this enzyme induces bacterial cell death. As a second round lead optimization design, new 1,2-naphthalein derivatives have been synthesized and tested against a TS-based biolibrary, including human thymidylate synthase (hTS). Docking studies have been performed to rationalize the experimentally observed affinity profiles of 1,2-naphthalein compounds toward Lactobacillus casei TS and hTS. The best TS inhibitors have been tested against a number of clinical isolates of Gram-positive-resistant bacterial strains. Compound 3,3-bis(3,5-dibromo-4-hydroxyphenyl)-1H,3H-naphtho[1,2-c]furan-1-one (5) showed significant antibacterial activity, no in vitro toxicity, and dose-response effects against Staphylococcus epidermidis (MIC=0.5-2.5 microg/mL) clinical isolate strains, which are resistant to at least 17 of the best known antibacterial agents, including vancomycin. So far this compound can be regarded as a leading antibacterial agent.


Diet and Polycystic Ovary Syndrome.
Polycystic ovary syndrome is a common endocrine disorder found in up to 10% of women. It can have profound metabolic consequences, including increased risk of diabetes and heart disease, if not treated. The majority of women with polycystic ovary syndrome are obese and many are insulin resistant. Diet, exercise, and weight loss play important roles in the treatment of polycystic ovary syndrome.


Food avoidance in patients with inflammatory bowel disease: What, when and who?
Patients with inflammatory bowel diseases avoid a variety of foods. However, it remains unclear how this behavior varies across patients. This cross-sectional study investigated how the food avoidance pattern in inflammatory bowel disease varies according to disease's activity, disease's subtype, Crohn's location, and prior history of bowel resection, strictures, and fistulae. Outpatients with Crohn's disease (n = 173) and ulcerative colitis (n = 72) reported which food they avoid when they perceive they are in remission or in active disease using a list of 82 food items classified in 10 categories. Medical charts were reviewed for patients' characteristics. Linear regression analyses were used to compare food exclusion rates between patients' subgroups and food categories. During remission, food exclusion rates varied from 1 to 39%. Most avoided foods were those with capsaicin, meat alternatives, and raw vegetables. Overall, food exclusion rates were 38% higher in Crohn's disease than ulcerative colitis (P < 0.001), and 50% higher in stricturing than non-stricturing Crohn's disease (P < 0.001). During active disease, food exclusion rates were 69% higher than in remission (P < 0.001). Similar differences between subgroups were again observed during active disease though less noticeable than in remission. No association was found with other disease characteristics. Avoided foods were very similar across patients except for alcoholic beverages and foods rich in dietary fibers/residue, which were avoided more specifically during active disease and in Crohn's disease, respectively. Food avoidance is common among patients with inflammatory bowel diseases, and most particularly in those with stricturing Crohn's disease. Specificities in avoidance pattern suggest that the clinical response to dietary restrictions may differ according to the disease's characteristics.


Aluminum and Molybdenum Co-Doped Zinc Oxide Films as Dual-Functional Carrier-Selective Contact for Silicon Solar Cells.
Aluminum-doped zinc oxide (AZO) is considered as a promising candidate as transparent conductive oxide (TCO) for silicon heterojunction solar cells due to its high carrier density, nontoxic nature, and low cost. Herein, it is presented that the transparency of the AZO film can be optimized through co-sputtering of AZO and molybdenum oxide (MoOx). Furthermore, aluminum and molybdenum co-doped zinc oxide (MAZO) can be used as both the TCO layer and electron-selective contact (ESC) for silicon heterojunction solar cells. The surface morphology, cation oxidation state, and optical and electrical properties of all MAZO films are characterized. It is found that the transmittance of all MAZO films is significantly increased at a wavelength of 450-800 nm due to MAZO with a stronger Zn-O bond and a wider band gap. The conductivity of MAZO films is approximate to AZO films at a low MoOx target deposit power (50 W), and the sheet resistance of MAZO films increases significantly by increasing the deposition power up to 100 W. Finally, the optimized MAZO films are used as TCO and ESC for silicon heterojunction solar cells, showing a power conversion efficiency of 19.58%. The results show an effective stage to improve the optical properties of AZO through co-doping and the possibility of applying MAZO as a dual-functional layer for silicon solar cells.


Nicorandil ameliorates mitochondrial dysfunction in doxorubicin-induced heart failure in rats: possible mechanism of cardioprotection.
Despite of its known cardiotoxicity, doxorubicin is still a highly effective anti-neoplastic agent in the treatment of several cancers. In the present study, the cardioprotective effect of nicorandil was investigated on hemodynamic alterations and mitochondrial dysfunction induced by cumulative administration of doxorubicin in rats. Doxorubicin was injected i.p. over 2 weeks to obtain a cumulative dose of 18 mg/kg. Nicorandil (3 mg/kg/day) was given orally with or without doxorubicin treatment. Heart rate and aortic blood flow were recorded 24 h after receiving the last dose of doxorubicin. Rats were then sacrificed and hearts were rapidly excised for estimation of caspase-3 activity, phosphocreatine and adenine nucleotides contents in addition to cytochrome c, Bcl2, Bax and caspase 3 expression. Moreover, mitochondrial oxidative phosphorylation capacity, creatine kinase activity and oxidative stress markers were measured together with the examination of DNA fragmentation and ultrastructural changes. Nicorandil was effective in alleviating the decrement of heart rate and aortic blood flow and the state of mitochondrial oxidative stress induced by doxorubicin cardiotoxicity. Nicorandil also preserved phosphocreatine and adenine nucleotides contents by restoring mitochondrial oxidative phosphorylation capacity and creatine kinase activity. Moreover, nicorandil provided a significant cardioprotection via inhibition of apoptotic signaling pathway, DNA fragmentation and mitochondrial ultrastructural changes. Interestingly, nicorandil did not interfere with cytotoxic effect of doxorubicin against the growth of solid Ehrlich carcinoma. In conclusion, nicorandil was effective against the development of doxorubicin-induced heart failure in rats as indicated by improvement of hemodynamic perturbations, mitochondrial dysfunction and ultrastructural changes without affecting its antitumor activity.


Differences in non-specific physical symptom levels and pressure pain thresholds between patients with masticatory myofascial pain and arthralgia.
Objective: To compare the levels of non-specific physical symptoms and pressure pain threshold (PPT) found in patients with masticatory myofascial pain with those found in patients with temporomandibular arthralgia alone. Methods: The study followed an observational and cross-sectional protocol. A total of 64 female patients were evaluated for the presence of painful TMD, non-specific physical symptom levels, and PPT. Results: The group of patients with masticatory myofascial pain presented a lower mean for PPT as well as a higher mean for standardized T-Scores for non-specific physical symptom levels. Conclusion: Statistically significant differences were found in non-specific physical symptom levels and PPT between patients with an exclusive diagnosis of masticatory myofascial pain and patients with a diagnosis, also exclusive, of temporomandibular arthralgia.


Brief Report: Mediation Analysis with an Ordinal Outcome.
The article presents concepts and methods for mediation analysis for an ordinal outcome. We give definitions of natural direct and indirect effects using counterfactuals for ordinal outcomes; in this context, there are potentially different effects for any two levels of the outcome, and we consider difference and ratio scales. The confounding assumptions required for identification are similar to that in the existing mediation analysis literature. We discuss different modeling strategies for estimation. Under a proportional odds model with a reference category that is common, the direct and indirect effects on a ratio scale can each be summarized by a single estimate and are available in closed form; otherwise the effects may differ across categories compared and can be obtained by numeric simulation methods.


Engineering analysis of biological variables: an example of blood pressure over 1 day.
Almost all variables in biology are nonstationarily stochastic. For these variables, the conventional tools leave us a feeling that some valuable information is thrown away and that a complex phenomenon is presented imprecisely. Here, we apply recent advances initially made in the study of ocean waves to study the blood pressure waves in the lung. We note first that, in a long wave train, the handling of the local mean is of predominant importance. It is shown that a signal can be described by a sum of a series of intrinsic mode functions, each of which has zero local mean at all times. The process of deriving this series is called the "empirical mode decomposition method." Conventionally, Fourier analysis represents the data by sine and cosine functions, but no instantaneous frequency can be defined. In the new way, the data are represented by intrinsic mode functions, to which Hilbert transform can be used. Titchmarsh [Titchmarsh, E. C. (1948) Introduction to the Theory of Fourier Integrals (Oxford Univ. Press, Oxford)] has shown that a signal and i times its Hilbert transform together define a complex variable. From that complex variable, the instantaneous frequency, instantaneous amplitude, Hilbert spectrum, and marginal Hilbert spectrum have been defined. In addition, the Gumbel extreme-value statistics are applied. We present all of these features of the blood pressure records here for the reader to see how they look. In the future, we have to learn how these features change with disease or interventions.


Accidental exposures to blood and other body fluids in a large academic medical center.
Healthcare workers' and students' exposures to blood-borne pathogens during a 1-year period (1997) at a large university academic medical center were analyzed. The university health manages the Blood-Borne Pathogen Post-Exposure Control Program at the university and treats all reported exposures of students, faculty, and staff. Comparative exposure rates for all categories of healthcare workers, the work site where injuries occurred, and the circumstances involved in 298 exposure incidents are outlined. A standardized postexposure prophylaxis protocol provides for definition of the health status of all known source patients and assessment of the potential need for treatment of the exposed clinician. Implications of the study for focusing on improvements in training healthcare workers in proper procedures and the use of personal protective equipment in dealing with blood-borne pathogens are discussed.


Real-World Experiences With a Direct-Acting Antiviral Agent for Patients With Hepatitis C Virus Infection.
Traditional hepatitis C virus treatment was limited by low cure rates, side effects, and stringent monitoring requirements. Sofosbuvir, a direct-acting antiviral agent with a cure rate of 96%, was introduced in 2013. However, trials frequently excluded patients with advanced liver disease and prior treatment experience. This study aims to elucidate the real-world cure rates and sofosbuvir safety profile. A retrospective cohort study was conducted at Kaiser Permanente Southern California involving patients with hepatitis C virus who received sofosbuvir treatment. Patients age 18 years and older were included, and pregnant patients were excluded. The primary end point was sustained virologic response at 12 weeks posttreatment. Secondary end points were safety and medication adherence. Multiple logistic regression analysis was used to compare patients with genotypes 1 and 2 infections. Of the 213 study patients, 42.3% had cirrhosis, and 38% were treatment-experienced. Most patients (69.5%) received dual therapy (sofosbuvir + ribavirin), whereas the remainder (30.5%) received triple therapy (sofosbuvir + ribavirin + interferon). The overall rate of sustained virologic response at 12 weeks posttreatment rate was 72.9% for genotype 1 infection, 64.7% in the treatment-experienced subgroup, and 66.7% in the cirrhosis subgroup. Rates of sustained virologic response at 12 weeks posttreatment for genotypes 2 and 3 were 90.8% and 55%, respectively. Most patients experienced anemia and fatigue. Women and patients with a lower baseline viral load were statistically more likely to be cured. Real-world cure rates were similar to rates seen in clinical trials for genotype 2 infection and lower for genotype 1 infection. Patients with genotype 1 and 3 infection did better with triple therapy compared with dual therapy. Patients tolerated therapy well with side effects, serious adverse events, and discontinuation rates similar to clinical trials. Women and patients with lower baseline hepatitis C viral load were more likely to achieve sustained virological response at 12 weeks posttreatment.


Glycine is used as a transmitter by decrementing expiratory neurons of the ventrolateral medulla in the rat.
The medullary respiratory network involves various types of respiratory neurons. The present study focused on possible inhibitory neurons called decrementing expiratory (E-DEC) neurons and aimed to determine whether their transmitter is glycine or GABA. In Nembutal-anesthetized, neuromuscularly blocked, and artificially ventilated rats we labeled E-DEC neurons with Neurobiotin and processed the tissues for detection of mRNA encoding either glycine transporter 2 (GLYT2) as a marker for glycinergic neurons or glutamic acid decarboxylase isoform 67 (GAD67) as a marker for GABAergic neurons, using in situ hybridization. Of 38 E-DEC neurons that were labeled, cranial motoneurons (n = 14), which were labeled as control, were negative for either GLYT2 mRNA (n = 10) or GAD67 mRNA (n = 4). The other E-DEC neurons (n = 24) were non-motoneurons. Sixteen of them were examined for GLYT2 mRNA, and the majority (11 of 16) was GLYT2 mRNA-positive. The remaining E-DEC neurons (n = 8) were examined for GAD67 mRNA, and all of them were GAD67 mRNA-negative. The GLYT2 mRNA-positive E-DEC neurons were located in the ventrolateral medulla spanning the Bötzinger complex (BOT), the rostral ventral respiratory group (VRG), and the caudal VRG. We conclude that not only E-DEC neurons of the BOT but also many E-DEC neurons of the VRG are inhibitory and use glycine as a transmitter. Although the present negative data cannot rule out completely the release of GABA or co-release of glycine and GABA from E-DEC neurons, several lines of evidence suggest that the glycinergic process is primarily responsible for the phasic inhibition of the respiratory network during the expiratory phase.


Formulation and Clients' Agency in Cognitive Behavioral Therapy.
The experience of loss of agency is one of the reasons for clients to go for psychotherapy. Enhancing clients' agency has been considered a fundamental factor for successful treatment in psychiatry and psychotherapy, yet few studies have investigated the interactional realization of how therapists do this in authentic psychotherapeutic encounters. Drawing on audio-recorded talk-in-interaction between clients and psychotherapists in cognitive behavioral therapy (CBT) encounters at a mental health center in China, this paper uses the method of conversation analysis to demonstrate how therapists ascribe agency positions to clients by issuing formulations of what the clients have just said. Two types of formulation were identified: affirmative formulations and challenging formulations. In the first type, the therapists highlight the positive aspect of the clients' description of their experiences and ascribe an agentic position to the clients. In the second, the therapists challenge the clients' implausible views and their non-agentic positioning of themselves. This study shows that the therapists' formulation could be employed to manage the epistemic difficulties associated with claiming knowledge about the clients' inner states and assessing their feelings. In this sense, the formulation is a robust interactional device in negotiating epistemic problems in addressing the clients' experiences and promoting their agency in therapy. However, it is noteworthy that in the challenging formulation, therapists claim privileged access to the clients' knowledge domain and challenge their prior epistemic status, which might run the risk of engendering clients' resistance.


Kinase domain autophosphorylation rewires the activity and substrate specificity of CK1 enzymes.
CK1s are acidophilic serine/threonine kinases with multiple critical cellular functions; their misregulation contributes to cancer, neurodegenerative diseases, and sleep phase disorders. Here, we describe an evolutionarily conserved mechanism of CK1 activity: autophosphorylation of a threonine (T220 in human CK1δ) located at the N terminus of helix αG, proximal to the substrate binding cleft. Crystal structures and molecular dynamics simulations uncovered inherent plasticity in αG that increased upon T220 autophosphorylation. The phosphorylation-induced structural changes significantly altered the conformation of the substrate binding cleft, affecting substrate specificity. In T220 phosphorylated yeast and human CK1s, activity toward many substrates was decreased, but we also identified a high-affinity substrate that was phosphorylated more rapidly, and quantitative phosphoproteomics revealed that disrupting T220 autophosphorylation rewired CK1 signaling in Schizosaccharomyces pombe. T220 is present exclusively in the CK1 family, thus its autophosphorylation may have evolved as a unique regulatory mechanism for this important family.


Contrasts between Antarctic and Arctic ozone depletion.
This work surveys the depth and character of ozone depletion in the Antarctic and Arctic using available long balloon-borne and ground-based records that cover multiple decades from ground-based sites. Such data reveal changes in the range of ozone values including the extremes observed as polar air passes over the stations. Antarctic ozone observations reveal widespread and massive local depletion in the heart of the ozone "hole" region near 18 km, frequently exceeding 90%. Although some ozone losses are apparent in the Arctic during particular years, the depth of the ozone losses in the Arctic are considerably smaller, and their occurrence is far less frequent. Many Antarctic total integrated column ozone observations in spring since approximately the 1980s show values considerably below those ever observed in earlier decades. For the Arctic, there is evidence of some spring season depletion of total ozone at particular stations, but the changes are much less pronounced compared with the range of past data. Thus, the observations demonstrate that the widespread and deep ozone depletion that characterizes the Antarctic ozone hole is a unique feature on the planet.


How type I interferons shape myeloid cell function in CNS autoimmunity.
The precise mechanisms underlying the effects of IFN-I in CNS autoimmunity remain poorly understood despite the long-standing use of these cytokines as first-line disease-modifying drugs in the treatment of RRMS, a chronic demyelinating CNS autoimmune disease. Systemic use of IFN-I results in pleiotropic immunomodulation linking the innate and adaptive immune responses. Recent research has demonstrated that in the setting of CNS autoimmunity, IFNs-I have multiple effects on myeloid cell subsets, such as circulating monocytes, granulocytes, DCs, and tissue macrophages, such as microglia. These diverse effects include changes in cell activation, maturation, antigen presentation, and cytokine production, thus influencing T cell differentiation and expansion, as well as the regulation of executive functions, such as apoptosis and phagocytosis. Moreover, current data suggest that the engagement of the IFNAR on myeloid cells changes the activation status of the inflammasome in a cell type-specific manner. Whereas most reports support primarily immune-suppressive effects of IFN-I on myeloid cells, endogenously produced, exogenously induced, and peripherally administered IFNs-I exert complex differential spatial effects during CNS autoimmune inflammation. Clearly characterizing the molecular and cellular basis of these effects promises to yield viable targets for a more directed, localized, cell type-specific IFN-I-based therapeutic approach. This kind of approach would allow for replacing the current treatment strategy in MS of broadly and unselectively altering all immune responses, regardless of their beneficial or detrimental nature.


Radioimmunoassay of estriol-16-glucuronide.
A specific radioimmunoassay of estriol-16-glucuronide has been developed, using an antiserum obtained by immunization of rabbits against estriol-16-glucuronide-BSA. The assay does not require hydrolysis, extraction and purification, but only a dilution of the crude sample. This constitutes the main advantage of the precedure. Accuracy, precision and sensitivity of the method are similar to those reported for other radioimmunoassays of estriol. Its specificity is good for the measurement of estriol-16-glucuronide in urine and in amniotic fluid, but not in serum of pregnant women, which apparently contains material interfering with the radioimmunoassay, at dilutions of less than 1/100. A significant correlation was observed between estriol-16-glucuronide and total estriol in urine during pregnancy; however, the contribution of the glucuronide to the total increases as pregnancy progresses, rising from 50% for a total of 5 mg/24 h to 85% for a total of 50 mg/24 h. The present radioimmunoassay can be used as a quick and reliable method for the measurement of urinary estriol-16-glucuronide in high risk pregnancies.


Perceived economic strain exacerbates the effect of paternal depressed mood on hostility.
Depression in fathers has been associated with impaired parenting, which, in turn, may function as a central environmental mechanism underlying the adverse effects of paternal depression on children's development. Despite this, evidence suggests that many depressed fathers are able to maintain positive relationships with their children, and little is known about factors associated with better or worse parenting outcomes when fathers experience depression. Using two waves of prospective, longitudinal data from a community sample of fathers and their high school-aged adolescent offspring (N = 324), perceived economic strain was examined as a moderator of the effect of fathers' depressive symptoms on subsequent observer ratings of hostile parenting behaviors. Among fathers experiencing high levels of economic strain, depressive symptoms at offspring age 15 were a significant predictor of hostility toward their adolescent sons at age 18, controlling for family demographics and previous hostile parenting behaviors. Findings and directions for future research are discussed in relation to contemporary models of intergenerational psychopathology transmission. (PsycINFO Database Record (c) 2013 APA, all rights reserved).


Ethanol production from cellulosic materials using cellulase-expressing yeast.
We demonstrate direct ethanol fermentation from amorphous cellulose using cellulase-co-expressing yeast. Endoglucanases (EG) and cellobiohydrolases (CBH) from Trichoderma reesei, and beta-glucosidases (BGL) from Aspergillus aculeatus were integrated into genomes of the yeast strain Saccharomyces cerevisiae MT8-1. BGL was displayed on the yeast cell surface and both EG and CBH were secreted or displayed on the cell surface. All enzymes were successfully expressed on the cell surface or in culture supernatants in their active forms, and cellulose degradation was increased 3- to 5-fold by co-expressing EG and CBH. Direct ethanol fermentation from 10 g/L phosphoric acid swollen cellulose (PASC) was also carried out using EG-, CBH-, and BGL-co-expressing yeast. The ethanol yield was 2.1 g/L for EG-, CBH-, and BGL-displaying yeast, which was higher than that of EG- and CBH-secreting yeast (1.6 g/L ethanol). Our results show that cell surface display is more suitable for direct ethanol fermentation from cellulose.