Disease activity and response assessment in psoriatic arthritis using the Disease Activity index for PSoriatic Arthritis (DAPSA). A brief review.
In this review we provide reasons to use joint specific composite measures of disease activity for psoriatic arthritis (PsA) rather than composite scores that combine several manifestations of psoriatic disease, including skin involvement. Based on a principal component analysis, which, indeed, excluded skin involvement as a major factor in PsA, the Disease Activity index for PSoriatic Arthritis (DAPSA) was validated using clinical trial and observational data. Further, disease activity states and response criteria were recently defined. The DAPSA is simply calculated by summing swollen + tender joint counts + patient pain + patient global assessments + CRP, using 66/68 joint counts. DAPSA has meanwhile been validated in other studies and has shown to have a very high level of validity, also when compared with joint sonography. Thus, DAPSA is useful in clinical practice, clinical trials and observational studies.


Routine testing of Mycoplasma genitalium and Trichomonas vaginalis.
Mycoplasma genitalium (MG) and Trichomonas vaginalis (TV) are common sexual transmitted infections (STI). However, most STI screening programmes do not include routinely detection of these pathogens. Consequently, epidemiological data about MG and TV in the general population is lacking. The current study aims to give insight into the prevalence of both infections, thereby guiding decisions whether testing for these pathogens should be included routinely. Between February 2013 and August 2015, all samples sent to the laboratory of Diakonessenhuis Utrecht for STI testing (i.e. testing for Chlamydia trachomatis (CT) and Neisseria gonorrhoeae (NG)) were additionally examined for the presence of MG and TV by means of a laboratory-developed RT-PCR. Samples were collected by our hospital or by regional general practitioners. A total of 5628 PCR's were evaluated. In 7.5%, one or more STI were detected. CT was found in 5% and MG was positive in 1.9%. NG was detected in 0.5% and TV was detected in 0.6% of the samples. CT was found more often in primary care than in hospital setting (9.7% vs. 3.0%, p < .05). The same was shown for NG (1.1% vs. 0.2%, p < .05). More men than women were positive for CT (11.2% vs. 3.8%, p < .05) and NG (1.4% vs. 0.3%, p < .05). MG is more prevalent than NG and TV in a regional Dutch population. Furthermore, TV is equally common as NG. Based on our prevalence data, including MG and TV in STI testing protocols should be considered in the future.


[Color loss evaluation of a dietary formulation in function of temperature, storage time and packaging].
Color loss of a dietetic formulae based on pumpkin (Cucurbita maxima), rice, hen and vegetable oils was evaluated. The product was under an accelerated test at temperatures of 40, 50 and 70 degrees C for a month. The kinetic reaction of color loss (quality loss indicator) was obtained with n = 1 and Ea = 11.5 Kcal/mol. The product was also stored for sixth months at temperatures of 25, 30, 35 and 40 degrees C using glass containers, laminated and composite cans (non metallic). The color was measured by a colorimetric method and by sensory evaluation under the defined conditions of time, temperature and package. The statistical analyses of the color loss measured by instrument was performed by a randomized block design with a significance level of p < 0.05. The results obtained both by the instrument and by the sensory evaluation method, showed that the temperature and storage time has significant effect (p < 0.05) on the other hand, the package does not have a significant effect. It was concluded from this study that the product could be stored for 6 months at temperatures below 35 degrees C without changes in color.


New Advances in the Management of Refractory Angina Pectoris.
Refractory angina is a significant clinical problem and its successful management is often extremely challenging. Defined as chronic angina-type chest pain in the presence of myocardial ischaemia that persists despite optimal medical, interventional and surgical treatment, current therapies are limited and new approaches to treatment are needed. With an ageing population and increased survival from coronary artery disease, clinicians will increasingly encounter this complex condition in routine clinical practice. Novel therapies to target myocardial ischaemia in patients with refractory angina are at the forefront of research and in this review we discuss those in clinical translation and assess the evidence behind their efficacy.


[Applications of nitrile converting enzymes in the production of fine chemicals].
Nitriles are an important type of synthetic intermediates in the production of fine chemicals because of their easy preparations and versatile transformations. The traditional chemical conversion of nitriles to carboxylic acids and amides is feasible but it requires relatively harsh conditions of heat, acid or alkali. Nitrile converting enzymes (nitrilase, nitrile hydratase and amidase) which are used as biocatalyst for the production of fine chemicals have attracted substantial interest because of their ability to convert readily available nitriles into the corresponding higher value amides or acids under mild conditions with excellent chemo-, regio- and stereo-selectivities. Many nitrile converting enzymes have been explored and widely used for the production of fine chemicals. In this paper, various examples of biocatalytic synthesis of pharmaceuticals and their intermediates, agrochemicals and their intermediates, food and feed additives, and other fine chemicals are presented. In the near future, an increasing number of novel nitrile converting enzymes will be screened and their potential in the production of useful fine chemicals will be further exploited.


A multimodality vascular imaging phantom with fiducial markers visible in DSA, CTA, MRA, and ultrasound.
The objective was to design a vascular phantom compatible with digital subtraction angiography, computerized tomography angiography, ultrasound and magnetic resonance angiography (MRA). Fiducial markers were implanted at precise known locations in the phantom to facilitate identification and orientation of plane views from three-dimensional (3-D) reconstructed images. A vascular conduit connected to tubing at the extremities of the phantom ran through an agar-based gel filling it. A vessel wall in latex was included around the conduit to avoid diffusion of contrast agents. Using a lost-material casting technique based on a low melting point metal, geometries of pathological vessels were modeled. During the experimental testing, fiducial markers were detectable in all modalities without distortion. No leak of gadolinium through the vascular wall was observed on MRA after 5 hours. Moreover, no significant deformation of the vascular conduit was noted during the fabrication process (confirmed by microtome slicing along the vessel). The potential use of the phantom for calibration, rescaling, and fusion of 3-D images obtained from the different modalities as well as its use for the evaluation of intra- and inter-modality comparative studies of imaging systems are discussed. In conclusion, the vascular phantom can allow accurate calibration of radiological imaging devices based on x-ray, magnetic resonance and ultrasound and quantitative comparisons of the geometric accuracy of the vessel lumen obtained with each of these methods on a given well defined 3-D geometry.


Long-term benefit of radon spa therapy in the rehabilitation of rheumatoid arthritis: a randomised, double-blinded trial.
This study investigates the effects of radon (plus CO2) baths on RA in contrast to artificial CO2 baths in RA rehabilitation using a double-blinded trial enrolling 134 randomised patients of an in-patient rehabilitative programme (further 73 consecutive non-randomised patients are not reported here). The outcomes were limitations in occupational context/daily living (main outcome), pain, medication and further quantities. These were measured before the start, after the end of treatment and quarterly in the year thereafter. Repeated-measures analysis of covariance (RM-ANCOVA) of the intent-to-treat population was performed with group main effects (GME) and group x course interactions (G x C) reported. Hierarchically ordered hypotheses ensured the adherence of the nominal significance level. The superiority of the radon treatment was found regarding the main outcome (RM-ANCOVA until 12 months: p(GME) = 0.15, p(G x C) = 0.033). Consumption of steroids (p(GME) = 0.064, p(G x C) = 0.025) and NSAIDs (p(GME) = 0.035, p(G x C) = 0.008) were significantly reduced. The results suggest beneficial long-term effects of radon baths as adjunct to a multimodal rehabilitative treatment of RA.


Clinical syndrome suggestive of heart failure is frequently attributable to non-cardiac disorders--population-based study.
To assess how often the clinical syndrome (CS) of heart failure is attributable to alternative, including non-cardiac, explanations. Cross-sectional evaluation of 739 community participants aged>or=45 years. Subjects with >or=2 symptoms or signs (dyspnoea or fatigue, orthopnoea, nocturnal paroxysmal dyspnoea, third heart sound, jugular venous distension, rales and lower limb oedema) or who were receiving loop diuretics were considered to have the clinical syndrome of heart failure. Attributable fractions were derived based on adjusted odds ratios and the prevalence of underlying disorders among cases. CS was present in 28.0% of women and in 15.2% of men, p<0.001. The multivariate-adjusted fraction of CS attributable to female gender was 40.6%, to age>or=65 years 28.5%, left ventricular systolic dysfunction, left ventricular dilatation or moderate-severe valvular disease 4.9%, diastolic dysfunction or atrial fibrillation 13.0%, obesity 22.6%, coronary heart disease 7.2% and chronic lung disease 6.9%. When additionally adjusting for depressive symptoms, the association with gender and age became much weaker, and 32% of cases were attributable to depressive symptoms. Forty-two percent of subjects with CS had cardiac abnormalities. In less than half of subjects with CS was systolic or diastolic heart failure confirmed. Female gender, older age, obesity and depressive symptoms accounted for the largest fraction of CS.


TRAIL expression up-regulated by interferon-gamma via phosphorylation of STAT1 induces myeloma cell death.
Although the cellular and molecular biological effects of interferon (IFN)-alpha have been well-investigated, the effects of IFN-gamma are less understood. Eleven human myeloma cell lines with various myeloma-specific chromosomal translocations and overexpression of oncogenes were cultured with 1000 U/ml of IFN-gamma. In the KMS-20 cells, which showed growth inhibition due to IFN-gamma, trail expression, status of the Janus kinase (JAK)/STAT pathway were analyzed. KMS-20 cells showed marked up-regulation of trail, activation of STAT1 and TRAIL hyperproduction induced by IFN-gamma. The effects of IFN-gamma on growth inhibition of KMS-20 cells were characterized by activation of the JAK/STAT signalling pathway, particularly STAT1 phosphorylation, enhanced secretion of TRAIL, and auto/paracrine usage of secreted TRAIL to induce apoptotic cell death. From these results, IFN-gamma may be considered one of the drugs to be used in future multidrug chemotherapeutic regimens for myeloma patients.


[Pressure pneumocephalus after posterior fossa surgery in the sitting position].
Pneumocephalus occurs commonly soon after intracranial surgery. When it presents as a significant increase in intracranial pressure it is called pressure pneumocephalus, a severe, life-threatening complication of neurosurgery that requires immediate treatment. Tension pneumocephalus must be suspected in patients unexpectedly fail to awaken at the end of surgery or who present progressive neurological deterioration after posterior fossa surgery. Diagnosis is by computerized axial thomography of the brain. Treatment is simple, consisting of promptly releasing the pressurized gas by trephination to save the patient's life or prevent severe neurological sequelae. We report two cases of pressure pneumocephalus that illustrate several risk factors: sitting position during surgery, preoperative hydrocephaly, surgical opening of the fourth ventricular and the presence of cerebrospinal shunt during surgery.


Multi-omics & pathway analysis identify potential roles for tumor N-acetyl aspartate accumulation in murine models of castration-resistant prostate cancer.
Castration-resistant prostate cancer (CRPC) is incurable and remains a significant worldwide challenge (Oakes and Papa, 2015). Matched untargeted multi-level omic datasets may reveal biological changes driving CRPC, identifying novel biomarkers and/or therapeutic targets. Untargeted RNA sequencing, proteomics, and metabolomics were performed on xenografts derived from three independent sets of hormone naive and matched CRPC human cell line models of local, lymph node, and bone metastasis grown as murine orthografts. Collectively, we tested the feasibility of muti-omics analysis on models of CRPC in revealing pathways of interest for future validation investigation. Untargeted metabolomics revealed NAA and NAAG commonly accumulating in CRPC across three independent models and proteomics showed upregulation of related enzymes, namely N-acetylated alpha-linked acidic dipeptidases (FOLH1/NAALADL2). Based on pathway analysis integrating multiple omic levels, we hypothesize that increased NAA in CRPC may be due to upregulation of NAAG hydrolysis via NAALADLases providing a pool of acetyl Co-A for upregulated sphingolipid metabolism and a pool of glutamate and aspartate for nucleotide synthesis during tumor growth.


Targeting human dendritic cells via DEC-205 using PLGA nanoparticles leads to enhanced cross-presentation of a melanoma-associated antigen.
Targeting antigen to dendritic cells (DCs) is a powerful and novel strategy for vaccination. Priming or loading DCs with antigen controls whether subsequent immunity will develop and hence whether effective vaccination can be achieved. The goal of our present work was to increase the potency of DC-based antitumor vaccines by overcoming inherent limitations associated with antigen stability and cross-presentation. Nanoparticles prepared from the biodegradable polymer poly(lactic-co-glycolic acid) have been extensively used in clinical settings for drug delivery and are currently the subject of intensive investigation as antigen delivery vehicles for vaccine applications. Here we describe a nanoparticulate delivery system with the ability to simultaneously carry a high density of protein-based antigen while displaying a DC targeting ligand on its surface. Utilizing a targeting motif specific for the DC-associated surface ligand DEC-205, we show that targeted nanoparticles encapsulating a MART-127-35 peptide are both internalized and cross-presented with significantly higher efficiency than isotype control-coated nanoparticles in human cells. In addition, the DEC-205-labeled nanoparticles rapidly escape from the DC endosomal compartment and do not colocalize with markers of early (EEA-1) or late endosome/lysosome (LAMP-1). This indicates that encapsulated antigens delivered by nanoparticles may have direct access to the class I cytoplasmic major histocompatibility complex loading machinery, overcoming the need for "classical" cross-presentation and facilitating heightened DC stimulation of anti-tumor CD8(+) T-cells. These results indicate that this delivery system provides a flexible and versatile methodology to deliver melanoma-associated antigen to DCs, with both high efficiency and heightened potency.


17β-estradiol inhibits mesenchymal stem cells-induced human AGS gastric cancer cell mobility via suppression of CCL5- Src/Cas/Paxillin signaling pathway.
Gender differences in terms of mortality among many solid organ malignancies have been proved by epidemiological data. Estrogen has been suspected to cast a protective effect against cancer because of the lower mortality of gastric cancer in females and the benefits of hormone replacement therapy (HRT) in gastric cancer. Hence, it suggests that 17β-estradiol (E2) may affect the behavior of cancer cells. One of the key features of cancer-related mortality is metastasis. Accumulating evidences suggest that human bone marrow mesenchymal stem cells (HBMMSCs) and its secreted CCL-5 have a role in enhancing the metastatic potential of breast cancer cells. However, it is not clear whether E2 would affect HBMMSCs-induced mobility in gastric cancer cells. In this report, we show that CCL-5 secreted by HBMMSCs enhanced mobility in human AGS gastric cancer cells via activation of Src/Cas/Paxillin signaling pathway. Treatment with specific neutralizing antibody of CCL-5 significantly inhibited HBMMSCs-enhanced mobility in human AGS gastric cancer cells. We further observe that 17β-estradiol suppressed HBMMSCs-enhanced mobility by down-regulating CCL5-Src/Cas/paxillin signaling pathway in AGS cells. Collectively, these results suggest that 17β-estradiol treatment significantly inhibits HBMMSCS-induced mobility in human AGS gastric cancer cells.


Peripheral atherosclerosis in patients with myocardial infarction.
In 260 patients with myocardial infarction the systolic blood pressure gradient from arm to big toe was used as an indirect measure of the degree of generalized atherosclerosis. Arterial insufficiency was found in 12 per cent of the men and in 17 per cent of the women studied. The two year mortality was 19 per cent in males with arterial insufficiency as against 6 per cent in males without arterial insufficiency. This difference increased with longer (56-82 months) follow-up. The number of women was smaller but the results were similar. The present study does not support the theory that most patients with myocardial infarction have generalized atherosclerosis. Indeed, this seems to be the case in only a small fraction of such patients, thus supporting the idea that other mechanisms are also important in the etiology of myocardial infarction.


Population model of bladder motion and deformation based on dominant eigenmodes and mixed-effects models in prostate cancer radiotherapy.
In radiotherapy for prostate cancer irradiation of neighboring organs at risk may lead to undesirable side-effects. Given this setting, the bladder presents the largest inter-fraction shape variations hampering the computation of the actual delivered dose vs. planned dose. This paper proposes a population model, based on longitudinal data, able to estimate the probability of bladder presence during treatment, using only the planning computed tomography (CT) scan as input information. As in previously-proposed principal component analysis (PCA) population-based models, we have used the data to obtain the dominant eigenmodes that describe bladder geometric variations between fractions. However, we have used a longitudinal analysis along each mode in order to properly characterize patient's variance from the total population variance. We have proposed is a mixed-effects (ME) model in order to separate intra- and inter-patient variability, in an effort to control confounding cohort effects. Other than using PCA, bladder shapes are represented by using spherical harmonics (SPHARM) that additionally enables data compression without information lost. Based on training data from repeated CT scans, the ME model was thus implemented following dimensionality reduction by means of SPHARM and PCA. We have evaluated the model in a leave-one-out cross validation framework on the training data but also using independent data. Probability maps (PMs) were thus generated with several draws from the learnt model as predicted regions where the bladder will likely move and deform. These PMs were compared with the actual regions using metrics based on mutual information distance and misestimated voxels. The prediction was also compared with two previous population PCA-based models. The proposed model was able to reduce the uncertainties in the estimation of the probable region of bladder motion and deformation. This model can thus be used for tailoring radiotherapy treatments.


[Studies on the diagnosis of insulinoma].
The results of various tests for the diagnosis and localization of insulinoma in ten patients were reviewed. The diagnostic criteria IRI X 100/(BS-30)greater than 50 and IRI/BS greater than 0.30 in the fast were most reliable in establishing a diagnosis of insulinoma. If a diagnosis of insulinoma is in doubt after several overnight fasts, C-peptide suppression test should be carried out since the test is safe and convenient. As insulin stimulation tests often lead to false-negative results and sometimes cause dangerous levels of hypoglycemia in patients with insulinoma, they are not widely recommended now. However they may be useful, if positive, in some patients with insulinoma who exhibit no abnormality in insulin-glucose ratio or C-peptide suppression test. Percutaneous transhepatic portal catheterization with measurements of radioimmunoreactive insulin concentration, supported by the clear theoretical grounds for interpretation of its results, was the most reliable method for preoperative localization of an insulinoma. Therefore the method, together with pancreatic angiography, should be attempted in all the patients with insulinoma. Insulinoma is an endocrine tumor curable by surgical removal, but there still remain a few unfortunate patients who have brain damages due to severe hypoglycemia or are blindly treated by pancreatectomy. Such cases should be eliminated by the early diagnosis and correct preoperative localization of the tumor.


Analyzing topography of membrane-inserted diphtheria toxin T domain using BODIPY-streptavidin: at low pH, helices 8 and 9 form a transmembrane hairpin but helices 5-7 form stable nonclassical inserted segments on the cis side of the bilayer.
Low pH-induced membrane insertion by diphtheria toxin T domain is crucial for A chain translocation into the cytoplasm. To define the membrane topography of the T domain, the exposure of biotinylated Cys residues to the cis and trans bilayer surfaces was examined using model membrane vesicles containing a deeply inserted T domain. To do this, the reactivity of biotin with external and vesicle-entrapped BODIPY-labeled streptavidin was measured. The T domain was found to insert with roughly 70-80% of the molecules in the physiologically relevant orientation. In this orientation, residue 349, located in the loop between hydrophobic helices 8 and 9, was exposed to the trans side of the bilayer, while other solution-exposed residues along the hydrophobic helices 5-9 region of the T domain located near the cis surface. A protocol developed to detect the movement of residues back and forth across the membranes demonstrated that T domain sequences did not rapidly equilibrate between the cis and the trans sides of the bilayer. Binding streptavidin to biotinylated residues prior to membrane insertion only inhibited T domain pore formation for residues in the loop between helices 8 and 9. Pore formation experiments used an approach avoiding interference from transient membrane defects/leakage that may occur upon the initial insertion of protein. Combined, these results indicate that at low pH hydrophobic helices 8 and 9 form a transmembrane hairpin, while hydrophobic helices 5-7 form a nonclassical deeply inserted nontransmembraneous state. We propose that this represents a novel pre-translocation state that is distinct from a previously defined post-translocation state.


Treatment motivation and therapeutic engagement in prison-based substance use treatment.
Studies of community-based substance use treatment show that motivation for treatment is critical for clients becoming therapeutically engaged. Little research, however, has been conducted on therapeutic engagement in corrections-based substance use treatment. The current study examines the association between internal treatment motivation and therapeutic engagement for a sample of 220 male substance-using offenders enrolled in a corrections-based treatment program. Findings showed that problem recognition and desire for help were associated with cognitive indicators of therapeutic engagement, specifically confidence in and commitment to treatment. Increased focus on internal motivation for treatment may lead to more effective treatment for substance-using offenders. Pretreatment motivational interventions therefore are recommended for substance-using offenders with low internal motivation for treatment.


A capacitive electrode with fast recovery feature.
Capacitive electrodes (CEs) allow for acquiring biopotentials without galvanic contact, avoiding skin preparation and the use of electrolytic gel. The signal quality provided by present CEs is similar to that of standard wet electrodes, but they are more sensitive to electrostatic charge interference and motion artifacts, mainly when biopotentials are picked up through clothing and coupling capacitances are reduced to tens of picofarads. When artifacts are large enough to saturate the preamplifier, several seconds (up to tens) are needed to recover a proper baseline level, and during this period biopotential signals are irremediably lost. To reduce this problem, a CE that includes a fast-recovery (FR) circuit is proposed. It works directly on the coupling capacitor, recovering the amplifier from saturation while preserving ultra-high input impedance, as a CE requires. A prototype was built and tested acquiring ECG signals. Several experimental data are presented, which show that the proposed circuit significantly reduces record segment losses due to amplifier saturation when working in real environments.


Emergency department visits of Syrian refugees and the cost of their healthcare.
The aim of this study was to evaluate the demographic and clinical characteristics of Emergency Department (ED) visits made by Syrian refugees and to assess the cost of their healthcare. This retrospective study was conducted in adult Syrians who visited the ED of Adiyaman University Training and Research Hospital, Adiyaman Province, Turkey, between 01 January and 31 December 2015. We evaluated 10,529 Syrian refugees who visited the ED, of whom 9,842 were included in the study. The number of ED visits significantly increased in 2015 compared with 2010; the increase in the proportion of total ED visits was 8% (n = 11,275, dif: 8%, CI 95%: 7.9- 8.2, p < 0.001). Of this 8%, 6.5% were visits made by Syria refugees and the remaining 1.5% accounted for the visits made by other individuals. Upper respiratory tract infections (URTI) were the diseases most frequently presented (n = 4,656; 47.3%), and 68.5% of ED visits were inappropriate (n = 6,749). The median ED length of stay (LOS) of the Syrian refugees was significantly longer than that of the other individuals visiting the ED (p < 0.001). The total cost of the healthcare of the Syrian refugees who visited the ED was calculated as US$ 773,374.63. This study showed that Syrian refugees have increased the proportion of ED visits and the financial healthcare burden. The majority of ED visits made by Syrian refugees were inappropriate. In addition, their ED LOS was longer than that of other individuals making ED visits.


Fast Computation of Born-Approximated Multistatic Scattering.
An algorithm for the fast computation of multistatic scattering patterns, produced by low-contrast inhomogeneous volumetric objects, which satisfy the Born approximation assumption, is presented. The algorithm relies on hierarchical interpolation and aggregation of optimally sampled phase-compensated partial contributions to the scattered field integral. The Born approximation enables the efficient simultaneous computation for ranges of incident and observation angles, as well as excitation frequencies. This leads to a reduction in the asymptotic computational complexity by several polynomial orders of the problem's acoustical size. The algorithm's error controllability and favorable computation time are demonstrated via representative examples.


Functional recovery after combined cerebral and cerebellar hemispherectomy in the rat.
The cerebellum seems to be one of the structures responsible for early neurological improvement after cerebral hemispherectomy and its consequent deficits. Considered as an accessory brain, the cerebellum may constitute a neurobiological substrate for the recovery of such extensive cortical and subcortical lesions. It may compensate for the injury by structural remodeling and plasticity. The authors observed that, indeed, rats submitted to contralateral hemicerebellectomy before cerebral hemispherectomy do not recover as well as those submitted to hemicerebellectomy 2 weeks after cerebral hemispherectomy.


Amnesia in temporal lobectomy patients: historical perspective and review.
Profound memory loss is a rare but serious complication of temporal-lobe surgery for the relief of medically intractable epilepsy. This paper examines the characteristics of the patients who have been reported to become amnesic following temporal-lobe surgery over the last four decades. The critical role of the hippocampi in memory function are implicated in autopsy studies and MRI investigations, but these cases suggest that a range of memory impairments result from bilateral hippocampal damage, rather than a pure amnesic syndrome in every case. There is some evidence that bilateral structural hippocampal abnormalities may not necessarily be associated with significant memory problems, if these abnormalities have a developmental basis. However, whilst not necessarily profound, any post-operative deterioration in memory function remains a significant consideration in the presurgical evaluation of temporal-lobe epilepsy patients.


[Characteristics of PD-L1 expression in tumor cells and tumor microenvironment of DLBCL with MYD88 L265P mutation].
Objective: To study the effect of MYD88 L265P mutation on the expression of PD-L1 in tumor cells and tumor microenvironment in diffuse large B-cell lymphoma (DLBCL), and to provide theoretical basis for immunotherapy for patients. Methods: Multiplex ligation-dependent probe amplification (MLPA) was used to detect the frequency of MYD88 L265P mutation in 72 cases of DLBCL diagnosed by pathologists in Cancer Hospital of Chinese Academy of Medical Sciences from August 2008 to May 2010. Expression of PD-L1 in tumor cells and tumor microenvironment in all samples was evaluated using PD-L1 (22C3) and PD-L1 (SP142) with Ventana automatic immunohistochemical (IHC) platform. The relationship between MYD88 L265P mutation and the expression of PD-L1 in DLBCL tumor cells and tumor microenvironment was assessed. Results: Of the 72 cases of DLBCL, MYD88 L265P mutation was detected in 15 (20.8%) cases. Nine cases with JAK2 amplification were excluded, and the remaining 63 cases of DLBCL were divided into MYD88 L265P mutant group (n=14) and MYD88 L265P wild-type group (n=49). IHC results showed that among the 14 cases of MYD88 L265P mutant groups, PD-L1 (22C3) was positive in 7 cases (7/14) of tumor cells and PD-L1 (SP142) was positive in 4 cases (4/14) of tumor microenvironment. Among the 49 cases of MYD88 L265P wild-type group, 9 cases (18.4%) were positive for PD-L1 (22C3) in tumor cells, and 38 cases (77.6%) were positive for PD-L1(SP142) in tumor microenvironment. In addition, among the 16 cases with PD-L1(22C3) expression in tumor cells, only 2 of the 7 cases with MYD88 L265P mutation were positive for PD-L1 (SP142) in tumor microenvironment. All 9 cases with wild-type MYD88 L265P were positive for PD-L1 (SP142) in tumor microenvironment. Statistical analysis showed that the expression level of PD-L1 (22C3) in tumor cells in the MYD88 L265P mutant group was significantly higher than that in the MYD88 L265P wild-type group (P=0.017). The expression level of PD-L1 (SP142) in tumor microenvironment in the MYD88 L265P mutant group was significantly lower than that in the MYD88 L265P wild-type group (P=0.001). Conclusions: MYD88 L265P mutation may play an important role in the regulation of PD-L1 expression in DLBCL tumor cells and tumor microenvironment. Further studies will provide a theoretical basis for immunotherapy of DLBCL patients with MYD88 L265P mutation.


Cranial fasciitis: nodular fasciitis of the head.
An infant was noted at birth to have a lesion over the left coronal suture fixed to both the skin and periosteum, which was identical histologically to nodular fasciitis. This lesion has been described in the literature in various locations, but rarely in the scalp, and not in newborns.


The taxation of unhealthy energy-dense foods (EDFs) and sugar-sweetened beverages (SSBs): An overview of patterns observed in the policy content and policy context of 13 case studies.
Taxation of energy-dense foods (EDFs) and sugar-sweetened beverages (SSBs) is increasingly of interest as a novel public health and fiscal policy instrument. However academic interest in policy determinants has remained limited. We address this paucity by comparing the policy content and policy context of EDF/SSB taxes witnessed in 13 case studies, of which we assume the tax is sufficiently high to induce behavioural change. The observational and non-randomized studies published on our case studies seem to indicate that the EDF/SSB taxes under investigation generally had the desired effects on prices and consumption of targeted products. The revenue collection of EDF/SSB taxes is minimal yet significant. Administrative practicalities in tax levying are important, possibly explaining why a drift towards solely taxing SSBs can be noted, as these can be demarcated more easily, with levies seemingly increasing in more recent case studies. Despite the growing body of evidence suggesting that EDF/SSB taxes have the potential to improve health, fiscal needs more often seem to lay their policy foundation rather than public health advocacy. A remarkable amount of conservative/liberal governments have adopted these taxes, although in many cases revenues are earmarked for benefits compensating regressive income effects. Governments voice diverse policy rationales, ranging from explicitly describing the tax as a public health instrument, to solely explicating revenue raising.


Small Bowel Obstruction Secondary to Acute Pancreatitis.
While an uncommon occurrence, it is possible for patients diagnosed with acute pancreatitis to develop colonic ileus, obstruction, or perforation. By extension, it is also possible to develop a small bowel obstruction following an episode of acute pancreatitis. Here, we present the case of a 44-year-old male, who after repeated attacks of acute pancreatitis, came to the emergency department with continuous, non-bloody vomiting. This patient also complained of both left upper quadrant and epigastric pain, and was subsequently diagnosed with a small bowel obstruction involving the proximal jejunum.


Reasons to have sex, personal goals, and sexual behavior during the transition to college.
Emerging adults (M = 18.99 years, SD = .50) completed cross-sectional questionnaires (N = 943) and targeted follow-up telephone surveys (N = 202) across the transition to college. Gender, personal goals (dating, friendship, academic), and past sexual behavior were examined as predictors of reasons to have and not to have sex. Men rated Self-focused reasons to have sex as more important; women rated Partner-focused reasons to have sex and Ethical reasons not to have sex as more important. Importance of Pregnancy/STD reasons not to have sex did not differ by gender. Before college entrance, sexual history and personal goals predicted endorsement of reasons for/against sex. Personal goals predicted first intercourse during freshman year. Limitations of the study include the single university sample and use of closed-ended self-report measures. Personal goals and reasons for/against sex are associated with sexual behavior and should be addressed in programs designed to promote sexual health among emerging adult college students.


CDK9 inhibitor CDKI-73 is synergetic lethal with PARP inhibitor olaparib in BRCA1 wide-type ovarian cancer.
Poly (adenosine diphosphate ribose) polymerase (PARP) inhibitors benefit a small percentage of ovarian cancer patients with homologous recombination (HR) deficiency (HRD), which greatly limits the applications of PARP inhibitors. Given the function of CDK9 in homologous recombination repair (HRR), here, we show how to extend the utility of PARP inhibitors in BRCA1-proficient ovarian cancer by targeting CDK9. We found that high CDK9 expression is associated with a higher tumor stage in epithelial ovarian cancer patients, and CDK9 is co-expressed with BRCA1 by analyzing a public database. By using a CDK9 inhibitor CDKI-73, we found that its combination with the PARP inhibitor olaparib significantly suppressed cell viability and colony formation and induced apoptosis in BRCA1-proficient ovarian cancer cells. Consistently, the combination treatment remarkably reduced the tumor growth in mouse xenograft models. We demonstrated that CDKI-73 could downregulate BRCA1 expression, resulting in hypersensitivity to olaparib in BRCA1-proficient ovarian cancer. Taken together, our results show a synergetic effect of CDKI-73 combined with olaparib in BRCA1-proficient ovarian cancer, facilitating the clinical use of CDK9 as a predictive biomarker to exploit PARP inhibitors.


AIE-based theranostic systems for detection and killing of pathogens.
Pathogenic bacteria, fungi and viruses pose serious threats to the human health under appropriate conditions. There are many rapid and sensitive approaches have been developed for identification and quantification of specific pathogens, but many challenges still exist. Culture/colony counting and polymerase chain reaction are the classical methods used for pathogen detection, but their operations are time-consuming and laborious. On the other hand, the emergence and rapid spread of multidrug-resistant pathogens is another global threat. It is thus of utmost urgency to develop new therapeutic agents or strategies. Luminogens with aggregation-induced emission (AIEgens) and their derived supramolecular systems with unique optical properties have been developed as fluorescent probes for turn-on sensing of pathogens with high sensitivity and specificity. In addition, AIE-based supramolecular nanostructures exhibit excellent photodynamic inactivation (PDI) activity in aggregate, offering great potential for not only light-up diagnosis of pathogen, but also image-guided PDI therapy for pathogenic infection.


Phylogeography of the Qinghai-Tibetan Plateau endemic Juniperus przewalskii (Cupressaceae) inferred from chloroplast DNA sequence variation.
The vegetation of the northeast Qinghai-Tibetan Plateau is dominated by alpine meadow and desert-steppe with sparse forests scattered within it. To obtain a better understanding of the phylogeography of one constituent species of the forests in this region, we examined chloroplast trnT-trnF and trnS-trnG sequence variation within Juniperus przewalskii, a key endemic tree species. Sequence data were obtained from 392 trees in 20 populations covering the entire distribution range of the species. Six cpDNA haplotypes were identified. Significant population subdivision was detected (G(ST) = 0.772, N(ST) = 0.834), suggesting low levels of recurrent gene flow among populations and significant phylogeographic structure (N(ST) > G(ST), P < 0.05). Eight of the nine disjunct populations surveyed on the high-elevation northeast plateau were fixed for a single haplotype (A), while the remaining, more westerly population, contained the same haplotype at high frequency together with two low frequency haplotypes (C and F). In contrast, most populations that occurred at lower altitudes at the plateau edge were fixed or nearly fixed for one of two haplotypes, A or E. However, two plateau edge populations had haplotype compositions different from the rest. In one, four haplotypes (A, B, D and E) were present at approximately equivalent frequencies, which might reflect a larger refugium in the area of this population during the last glacial period. Phylogenetic analysis indicated that the most widely distributed haplotype A is not ancestral to other haplotypes. The contrasting phylogeographic structures of the haplotype-rich plateau edge area and the almost haplotype-uniform plateau platform region indicate that the plateau platform was recolonized by J. przewalskii during the most recent postglacial period. This is supported by the findings of a nested clade analysis, which inferred that postglacial range expansion from the plateau edge followed by recent fragmentation is largely responsible for the present-day spatial distribution of cpDNA haplotypes within the species.


Psychoanalysis and Telepathic Processes.
Freud's writing on the topic of thought-transference stimulated controversy among analysts and original reflection on psychoanalytic understandings of the psyche. The notion of telepathy has also contributed significantly to the development of fundamental psychoanalytic concepts, including transference, projective identification, and primary forms of symbolization processes. The notion of telepathy, especially in light of current trends in post-Bionian and field theories, is used to outline an epistemological framework in which the clinical relevance of this notion becomes clear. Epistemological questions raised by telepathy and how this notion relates to the most originary and primary forms of the intersubjective relationship are addressed before questioning the conditions for the emergence of telepathy, its integration within contemporary psychoanalytic theory, and its ontological nature.


Invited Commentary: Screening for hepatitis B in the immigrant population and individuals who are in need of immunosuppressive drug therapy.
Chronic hepatitis B (CHB) afflicts approximately 300 million people in the world. Hepatitis B virus (HBV) is a known carcinogenic virus and continues to be the leading cause of hepatocellular carcinoma (HCC) (1). Approximately 70% of hepatitis B surface antigen (HBsAg) carriers reside in intermediate (>2% prevalence) to high-risk (>8% prevalence) areas such as Asia, the Pacific Islands, Africa, India, and parts of Southern Europe (1). There is a common misperception that this disorder is not very common in the United States. However, 63% of the nearly 28 million immigrants who entered the US between 1974 and 2008 were born in countries of intermediate or high prevalence (2). The Immigrant Refugee and Migrant Health Branch of the Centers for Disease Control and Prevention (CDC) estimated that an average of 53,000 CHB cases were imported to the US yearly from 2004 to 2008. Forty percent of these cases originated from China, Vietnam, and the Philippines (2). The CDC has recently revised its prevalence estimates and concluded that 2.2 million US residents are likely to have chronic HBV infection, of which 1.3 million are judged to be foreign-born individuals. Even these figures are likely to be too low, however, because the estimates do not take into account illegal immigrants and other socially disadvantaged patients. Importantly, HBsAg testing is not required as part of the process of immigrating into the United States (3). This lack of a requirement for HBV screening is an important missed opportunity to programmatically diagnose this condition.


Bioactivation of α,β-Unsaturated Carboxylic Acids Through Acyl Glucuronidation.
After oral administration to monkeys of [14C]GDC-0810, an α,β-unsaturated carboxylic acid, unchanged parent and its acyl glucuronide metabolite, M6, were the major circulating drug-related components. In addition, greater than 50% of circulating radioactivity in plasma was found to be nonextractable 12 hours post-dose, suggesting possible covalent binding to plasma proteins. In the same study, one of the minor metabolites was a cysteine conjugate of M6 (M11) that was detected in plasma and excreta (urine and bile). The potential mechanism for the covalent binding to proteins was further investigated using in vitro methods. In incubations with glutathione (GSH) or cysteine (5 mM), GSH and cysteine conjugates of M6 were identified, respectively. The cysteine reaction was efficient with a half-life of 58.6 minutes (k react = 0.04 1/M per second). Loss of 176 Da (glucuronic acid) followed by 129 Da (glutamate) in mass fragmentation analysis of the GSH adduct of M6 (M13) suggested the glucuronic acid moiety was not modified. The conjugation of N-glucuronide M4 with cysteine in buffer was >1000-fold slower than with M6. Incubations of GDC-0810, M4, or M6 with monkey or human liver microsomes in the presence of NADPH and GSH did not produce any oxidative GSH adducts, and the respective substrates were qualitatively recovered. In silico analysis quantified the inherent reactivity differences between the glucuronide and its acid precursor. Collectively, these results show that acyl glucuronidation of α,β-unsaturated carboxylic acids can activate the compound toward reactivity with GSH, cysteine, or other biologically occurring thiols and should be considered during the course of drug discovery. SIGNIFICANCE STATEMENT: Acyl glucuronidation of the α,β-unsaturated carboxylic acid in GDC-0810 activates the conjugated alkene toward nucleophilic addition by glutathione or other reactive thiols. This is the first example that a bioactivation mechanism could lead to protein covalent binding to α,β-unsaturated carboxylic acid compounds.


Molecular epidemiology and drug resistant mechanism in carbapenem-resistant Klebsiella pneumoniae isolated from pediatric patients in Shanghai, China.
Infection by carbapenem-resistant Klebsiella pneumoniae (CR-KP) is a public health challenge worldwide, in particular among children, which was associated with high morbidity and mortality rates. There was limited data in pediatric populations, thus this study aimed to investigate molecular epidemiology and drug resistant mechanism of CR-KP strains from pediatric patients in Shanghai, China. A total of 41 clinical CR-KP isolates from sputum, urine, blood or drainage fluid were collected between July 2014 and May 2015 in Shanghai Children's Medical Center. Multilocus sequence typing (MLST), antibiotic susceptibility testing, PCR amplification and sequencing of the drug resistance associated genes were applied to all these isolates. MLST analysis revealed 16 distinct STs identified within the 41 isolates, among which the most frequently represented were ST11(19.5%),ST25(14.6%),ST76(14.6%),ST37(9.8%).One new ST was first identified. All CR-KP isolates showed MDR phenotypes and were resistance to ceftazidime, imipenem, piperacillin / tazobactam, ceftriaxone, ampicillin /sulbactam, aztreonam. They were confirmed as carbapenemase producer, NDM-1 (56.1%, 23/41), IMP (26.8%, 11/41), KPC-2 (22.0%, 9/41) were detected. Of note, two isolates carried simultaneously both NDM-1 and IMP-4. All CR-KP strains contained at least one of extended spectrum β-lactamase genes tested(TEM, SHV, OXA-1, CTX-M group) and six isolates carried both ESBL and AmpC genes(DHA-1). Among the penicllinase and β-lactamase genes, the most frequently one is SHV(92.7%,38/41), followed by TEM-1(68.3%,28/41), CTX-M-14(43.9%,18/41), CTX-M-15(43.9%,14/41), OXA-1(14.6%,6/41). In the present study, NDM-1-producing isolates was the predominant CR-KP strains in children, follow by IMP and KPC-producing strains. NDM-1and IMP-4 were more frequent than KPC-2 and showed a multiclonal background. Those suggested carbapenem-resistant in children is diverse, and certain resistance mechanisms differ from prevalent genotypes in adults in the same region. Knowledge of the molecular epidemiology and drug resistant mechanism of CR-KP can have a profound effect on clinical treatment, infection control measures and public health policies for children.


Fates of Administered Selenium Compounds.
The selenium analogues of the sulfur-containing amino acids are important tools for tracing the course of selenium from ingested food to functional proteins in the animal.


Efficacy of alanyl glutamine in nutritional support therapy for patients with sepsis: A protocol for systematic review and meta-analysis.
Sepsis is a systemic inflammatory response caused by infection, which is a common complication after severe infection, trauma, shock, and surgery, and is also an important factor in inducing septic shock and multiple organ dysfunction syndrome (MODS), and has become one of the important causes of death in critically ill patients. Septic patients with gastrointestinal transport function weakened, are prone to malnutrition, resulting in decreased immune function, thereby affecting the therapeutic effect. Clinical practice shows that the nutritional metabolism and immune response of patients with sepsis can be effectively improved by giving alanyl glutamine nutritional support treatment, but there is no evidence of evidence-based medicine. The study carried out in this protocol aims to evaluate the effectiveness of alanyl glutamine in nutritional support therapy for patients with sepsis. The Cochrane Library, PubMed, Embase, Web of Science, WHO International Clinical Trials Registry Platform, CNKI, CBM, VIP, and Wanfang databases were searched by computer, to retrieve all randomized controlled trials (RCTs) on nutritional support for the treatment of sepsis with alanyl glutamine from the date of database establishment to December 2020. Two researchers independently selected the study, extracted and managed the data. RevMan5.3 software was used to analyze the included literature. This study observed the changes of serum albumin (ALB), prealbumin (PAB), hemoglobin (Hb), C-reactive protein (CRP), immunoglobulin (IgG, IgA, and IgM), APACHE II score before and after treatment to evaluate the efficacy of alanyl glutamine in nutritional support therapy for patients with sepsis. This study will provide reliable evidence for the application of alanyl glutamine in nutritional support therapy for patients with sepsis. DOI 10.17605/OSF.IO/VRZPJ.


Concurrent validity and clinical utility of the HCR-20V3 compared with the HCR-20 in forensic mental health nursing: similar tools but improved method.
The main scope of this small-scale investigation was to compare clinical application of the HCR-20V3 with its predecessor, the HCR-20. To explore concurrent validity, two experienced nurses assessed 20 forensic mental health service patients with the tools. Estimates of internal consistency for the HCR-20 and the HCR-20V3 were calculated by Cronbach's alpha for two levels of measurement: the H-, C-, and R-scales and the total sum scores. We found moderate (C-scale) to good (H- and R- scales and aggregate scores) estimates of internal consistency and significant differences for the two versions of the HCR. This finding indicates that the two versions reflect common underlying dimensions and that there still appears to be differences between V2 and V3 ratings for the same patients. A case from forensic mental health was used to illustrate similarities and differences in assessment results between the two HCR-20 versions. The case illustration depicts clinical use of the HCR-20V3 and application of two structured nursing interventions pertaining to the risk management part of the tool. According to our experience, Version 3 is superior to Version 2 concerning: (a) item clarity; (b) the distinction between presence and relevance of risk factors; (c) the integration of risk formulation and risk scenario; and (d) the explicit demand to construct a risk management plan as part of the standard assessment procedure.


Laparoscopic sleeve gastrectomy using the LiVac liver retractor system: technical report.
Exposure of the angle of His (AOH) with liver retraction is one of the key processes during laparoscopic sleeve gastrectomy (LSG). A new internal liver retractor, the LiVac (LiVac, Pty Ltd.) has recently been introduced. This study was conducted to evaluate the feasibility of the LiVac in LSG. We applied the LiVac in 20 patients who received LSG. The feasibility was assessed by exposure of the AOH, operation time, complications, and changes of aspartate transaminase and alanine transaminase. In all 20 patients, exposure of the AOH was successful. The mean operation time was 88 minutes. The changes in preoperative and postoperative aspartate transaminase and alanine transaminase levels were 18.6 and 9.1 U/L, respectively. There were no related morbidities. In LSG, exposure of the AOH using the LiVac was technically feasible.


Beta-thromboglobulin levels in the nephrotic syndrome.
Beta-thromboglobulin (BTG), a platelet-specific protein released on platelet aggregation, was measured in 13 patients with clinical and biochemical evidence of the nephrotic syndrome. All 13 patients had increased concentrations of BTG compared to both 10 normal controls and to 12 non-nephrotic azotemic patients (p < 0.001). In five patients with the nephrotic syndrome in remission, the BTG levels returned to normal. These results support the contention that the nephrotic syndrome is associated with a state of hypercoagulability and suggest that increased platelet aggregation may be the primary underlying mechanism.


A comparison study on Acid Red 119 dye removal using two different types of waterworks sludge.
This study aims to compare the performance of two waterworks sludge samples, ferric chloride sludge (FCS) and polyaluminium chloride sludge (PACS), as coagulants to remove Acid Red 119 (AR119) dye from aqueous solution. A series of batch experiments were performed to investigate the effect of initial pH, coagulant dosage and initial dye concentration on coagulation/flocculation process efficiency. Results showed that the dye removal was strongly pH-dependent and followed the same trend for both coagulants, increasing steadily with decreasing initial pH in the range of 3-12. With the increase of coagulant dosage, the dye removal efficiency increased and no re-stabilization phenomenon was observed. However, the coagulant dosage needed for the maximum dye removal efficiency was much lower for FCS (150 mg dried sludge/L) in compare with PACS (5.5 g dried sludge/L). It seems that both charge neutralization and sweep flocculation mechanisms were involved in removal of AR119 using FCS and PACS. With the increase of initial dye concentration, Q (the amount of the removed dye per unit mass of coagulant) steadily increased and reached to a maximum value of 0.96 mg dye/mg sludge and 0.029 mg dye/mg sludge for FCS and PACS, respectively. FCS was more effective than PACS for AR119 dye removal due to the higher amount of dye removed per unit mass of sludge.


Modifying potential of thirty-one chemicals on the short-term development of gamma-glutamyl transpeptidase-positive foci in diethylnitrosamine-initiated rat liver.
The modifying potential of 31 different compounds on the development of gamma-glutamyl transpeptidase-positive (gamma-GT+) liver cell lesions was compared in an in vivo short-term assay system. Rats were initially given a single dose (200 mg/kg) of diethylnitrosamine intraperitoneally and 2 weeks later were treated with test compounds for 6 weeks and then sacrificed, all rats being subjected to partial hepatectomy at week 3. Modifying potential was scored by comparing the number and area (mm2)/cm2 of induced gamma-GT+ foci with those of the corresponding control group given DEN alone. 2-Acetylaminofluorene, 3'-methyl-4-dimethylaminoazobenzene, dimethylnitrosamine, phenobarbital, barbital, dipyrone and deoxycholic acid caused a significant enhancement of both the number and area of foci. 4-Acetylaminofluorene, ethionine, benzo[alpha]pyrene, disulfiram and cholic acid had a moderate enhancing effect, whereas slight, but not unequivocal, increases in gamma-GT+ foci were observed after captafol, glutathione, sodium ascorbate and taurine administration. In contrast, acetaminophen, ethoxyquin, butylated hydroxyanisole, butylated hydroxytoluene, and ethyl alcohol showed clear inhibitory effects. It is concluded that the present short-term in vivo system has practical application for the screening of modifying agents for liver tumorigenesis including hepatocarcinogens.


Long term treatment of steroid dependent asthmatic patients with beclomethasone dipropionate.
In the efforts to avoid the side-effects of the peroral cortisone drugs in the treatment of asthma, trials have been made since the early fifties with the administration of steroids in aerosol form applied direct on the bronchial mucosa. Hydrocortisone as well as prednisolone and dexamethasone have been used with a documented effect on the obstruction. However, the drugs were found to be resorbed and thus resulted in suppression of adrenal function and appearance of Cushing syndrome and other well-known steroid side-effects (12). More recently, beclomethasone dipropionate -- a steroid with potent topical activity -- has been used as a pressurised aerosol. In 1972 Morrow Brown et al. (1) as well as Lal et al. (10) reported a good therapeutic effect with this drug and at the same time found evidence for the opinion that its systemic effect, if any, was insignificant. Less ositive results were reported by Choo-Kang et al. (4) and also by Herxheimer (8), who considered beclomethasone spray not to possess any advantages as compared with the earlier steroids. The purpose of the present study was to assess the clinical value of beclomethasone in the treatment of adult patients previously on long-term oral steroids.


A mental model for early arithmetic.
The authors examined young children's ability to solve nonverbal calculation problems in which they must determine how many items are in a hidden array after items have been added into or taken away from it. Earlier work showed that an ability to reliably solve such problems emerges earlier than verbal calculation ability but did not examine when it first appears. The authors propose that the ability to solve such problems involves domain-general symbolic processes similar to those involved in symbolic play and the use of physical models. Hence the ability to calculate should appear at about 2 years and should be related to overall level of intellectual competence. The authors show that the ability to reliably solve nonverbal calculation tasks emerges only after 2 years of age and that performance on nonverbal calculation problems is highly related to overall level of intellectual competence in children between 3 and 4 years of age.


Laparoscopic microsurgical anastomosis of the blocked, solitary post-ectopic Fallopian tube: case report.
The surgical options for the management of ectopic pregnancy include linear salpingotomy or salpingectomy. If salpingotomy is performed, subsequent tubal blockage may result and if this occurs in a solitary Fallopian tube then assisted reproductive technology is recommended as the treatment of choice. We describe a case report detailing the application of laparoscopic microsurgical tubal reanastomosis in two patients with post-ectopic blockage in a solitary Fallopian tube. Both patients conceived post-operatively and subsequently delivered term pregnancies. Laparoscopic microsurgery offers an alternative to assisted reproductive technology in patients with post-ectopic tubal obstruction in a single Fallopian tube.


Histological Manifestations of Diabetic Kidney Disease and its Relationship with Insulin Resistance.
Histological manifestations of diabetic kidney disease (DKD) include mesangiolysis, mesangial matrix expansion, mesangial cell proliferation, thickening of the glomerular basement membrane, podocyte loss, foot process effacement, and hyalinosis of the glomerular arterioles, interstitial fibrosis, and tubular atrophy. Glomerulomegaly is a typical finding. Histological features of DKD may occur in the absence of clinical manifestations, having been documented in patients with normal urinary albumin excretion and normal glomerular filtration rate. Furthermore, the histological picture progresses over time, while clinical data may remain normal. Conversely, histological lesions of DKD improve with metabolic normalization following effective pancreas transplantation. Insulin resistance has been associated with the clinical manifestations of DKD (nephromegaly, glomerular hyperfiltration, albuminuria, and kidney failure). Likewise, insulin resistance may underlie the histological manifestations of DKD. Morphological changes of DKD are absent in newly diagnosed type 1 diabetes patients (with no insulin resistance) but appear afterward when insulin resistance develops. In contrast, structural lesions of DKD are typically present before the clinical diagnosis of type 2 diabetes. Several heterogeneous conditions that share the occurrence of insulin resistance, such as aging, obesity, acromegaly, lipodystrophy, cystic fibrosis, insulin receptor dysfunction, and Alström syndrome, also share both clinical and structural manifestations of kidney disease, including glomerulomegaly and other features of DKD, focal segmental glomerulosclerosis, and C3 glomerulopathy, which might be ascribed to the reduction in the synthesis of factor H binding sites (such as heparan sulfate) that leads to uncontrolled complement activation. Alström syndrome patients show systemic interstitial fibrosis markedly similar to that present in diabetes.


Ectopic localization of auxin and cytokinin in tobacco seedlings by the plant-oncogenic AK-6b gene of Agrobacterium tumefaciens AKE10.
The oncogenic 6b gene of Agrobacterium tumefaciens induces a number of morphological and metabolic alterations in plants. Although molecular functions associated with the 6b genes have been proposed, including auxin transport, sugar transport, transcriptional regulation, and miRNA metabolism, so far an unequivocal conclusion has not been obtained. We investigated the association between auxin accumulation and tumor development of the tobacco seedlings expressing the AK-6b gene under the control of the dexamethasone-inducible promoter. Indole-3-acetic acid (IAA) localization was examined by immunochemical staining with monoclonal antibody against IAA and by histochemical analysis using the IAA-specific induced construct, DR5::GUS (β-glucuronidase). Both procedures indicated that IAA preferentially accumulated in the tumorous protrusions as well as in newly developing vascular bundles in the tumors. Furthermore, true leaves also showed abaxial IAA localization, leading to altered leaves in which the adaxial and abaxial identities were no longer evident. Co-localization of cytokinin and auxin in the abaxial tumors was verified by immunochemical staining with an antibody against cytokinin. Treatment of AK-6b-seedlings with N-1-naphthylphthalamic acid, an inhibitor of polar auxin transport, promoted the morphological severity of phenotypes, whereas 1-naphthoxyacetic acid, a specific auxin influx carrier inhibitor, induced tumor regression on cotyledons and new tumorous proliferations on hypocotyls. Prominent accumulation of both auxin and cytokinin was observed in both regressed and newly developing tumors. We suggest from these results that modulation of auxin/cytokinin localization as a result of AK-6b gene expression is responsible for the tumorous proliferation.


The Graham Jackson Memorial Lecture ISSM 2016-"The Man Who Knew Too Much": Time to Recognize Erectile Dysfunction and Low Testosterone as Independent Risk Factors for Cardiovascular Disease.
Graham Jackson introduced the concept that erectile dysfunction (ED) is a marker for undiagnosed cardiovascular (CV) disease and future events. In the Princeton 3 guidelines, he recognized the important impact of testosterone deficiency (TD) on all-cause and CV mortality. Recent evidence suggests that testosterone therapy to target levels and for sufficient duration decreases CV events. Unfortunately, this had a modest impact on CV disease management because ED is not incorporated into current risk calculators. This report is based on the Graham Jackson Memorial Lecture presented at the International Society for Sexual Medicine (ISSM) in Beijing in 2016. To examine recent evidence as to whether ED should be upgraded to a risk factor, especially with the high predictive value in younger men, and to develop a case for TD to be considered an independent risk factor based on a large number of long-term studies during the past 5 years. A Medline search was undertaken to include articles on ED and TD and related terms from 1998 to 2016 during the preparation of ISSM guidelines on ED and TD. A rational justification for ED and low testosterone to be considered risk factors for CV disease and be included in risk calculators. The evidence for inclusion of ED and TD might be stronger than for accepted risk factors and have the advantages of being easily assessed, quantitative, symptomatic, and clinically relevant, especially in younger men. Because important studies are often published in endocrine, sexual medicine, urology, and cardiology journals, a multidisciplinary approach is needed. There is strong evidence that ED and low testosterone might be of more practical relevance to programs that decrease CV risk than some current recognized risk factors. Hackett G. The Graham Jackson Memorial Lecture ISSM 2016-"The Man Who Knew Too Much": Time to Recognize Erectile Dysfunction and Low Testosterone as Independent Risk Factors for Cardiovascular Disease. Sex Med Rev 2017;5:256-265.


Extracranial surgery for vertebro-basilar ischaemia (experience of 8 cases).
Atheromatous lesions of the proximal vertebral artery and the subclavian artery may lead to ischaemic manifestations, occasionally with severe consequences in the vertebro-basilar territory. These transient ischaemic attacks are most often caused by haemodynamic insufficiency rather than thrombo-embolic complications addressed by anticoagulant and antiaggregant treatments. In this study, 8 cases of vertebro-basilar ischaemia (VBI), secondary to subclavian and proximal vertebral artery lesions, are reported. Surgical techniques, subclavian-to-subclavian artery by-pass (5 cases) and vertebral to common carotid artery transposition (3 cases) are described with their respective results. Through a review of the literature, the various operative modalities are discussed in the different pathological conditions of the proximal extracranial vertebro-basilar disease. It appears that the subclavian to subclavian artery by-pass as well as the vertebral-to-common carotid artery transposition are safe surgical procedures with strikingly low morbidity and mortality rates. The widely achieved relief of the ischaemic episodes, undoubtedly makes this surgery an alternative to medical treatment.


Effects of somatosensory cortical stimulation on expression of c-Fos in rat medullary dorsal horn in response to formalin-induced noxious stimulation.
We examined the effects of epidural electrical stimulation of primary (SI) and secondary (SII) somatosensory cortex on expression of c-Fos protein in rat medullary dorsal horn neurons (Vc; trigeminal nucleus caudalis) in response to formalin-induced noxious stimulation. Epidural electrical stimulation (single pulse, 0.2 msec duration at 10 Hz) was applied to the left facial region SI or SII at three different stimulus intensities, 0.1, 0.5, and 1.0 mA for 60 min 0 or 2 hr after bilateral injection of formalin into the lower lip. SII stimulation at 1.0 mA immediately after injection of formalin, significantly decreased the number of Fos-positive cells in the right VcI/II by 32.4%. There was no significant change in the number of Fos-positive cells in the VcIII/IV. SII stimulation at 0.5 and 1.0 mA 2 hr after injection of formalin, significantly decreased the number of Fos-positive cells in the right VcI/II by 47.9% and 40.8%, but significantly increased the number of Fos-positive cells in the right VcIII/IV by 178.8% and 324.3%, respectively. In contrast, SI stimulation had no effect on expression of c-Fos in Vc. Possible direct corticotrigeminal projections were labeled anterogradely by injection of WGA-HRP into the SI and SII. In the Vc, labeled terminals were distributed mostly in the contralateral medial half of VcIII/IV and medullary reticular nucleus dorsalis but rarely in VcI/II. These results suggest that activation of SII-medullary fibers suppress nociceptive information from the oro-facial regions.


Decisions around Long-term Ventilation for Children. Perspectives of Directors of Pediatric Home Ventilation Programs.
The decision of whether to initiate or forgo long-term ventilation (LTV) for children with life-limiting conditions can be complex and impactful. Providers are responsible for helping families to understand the consequences of their options and guiding them through shared decision-making, but little has been published on how to do this. To assess how directors of pediatric home ventilation programs facilitate shared decision-making with families facing decisions of whether to initiate or forgo LTV for their children with life-limiting conditions. In addition, to assess directors' perspectives on these families' decisional needs. Purposeful recruiting of directors/codirectors of pediatric home ventilation programs at children's hospitals was used. We performed semistructured interviews using an open-ended interview guide developed de novo to assess their approach to informed, shared decision-making around LTV and their perspectives on these decisions. Qualitative data analysis was conducted using a thematic approach based on framework analysis in which thematic saturation was achieved. A sample of 15 experienced physician directors across North America was interviewed. All (15/15) inform families of the potential benefits and burdens/risks of LTV for the child and of the option to forgo LTV. All stress to families the physical, emotional, and social impact of caring for a child using LTV on the family; 12 directors also highlight the financial impact. All recommend that decision-making around LTV should be interdisciplinary, initiated early, and not rushed; nine described their approach as guided by the family's goals for the child and their family. All recommend that providers be transparent, candid, active listeners, and supportive. All directors believe that the family's decision should be respected, but vary in the extent to which they recommend an option to families. They described barriers to decision-making that stem from families, providers, and other sources. As providers who follow children using LTV, directors of pediatric home ventilation programs have perspectives regarding the decisional needs of these families and how to meet them that can help inform and shape the practices of other providers who assist families facing this decision.


Impaired Hippocampal Glutamate and Glutamine Metabolism in the db/db Mouse Model of Type 2 Diabetes Mellitus.
Type 2 diabetes mellitus (T2DM) is a risk factor for the development of Alzheimer's disease, and changes in brain energy metabolism have been suggested as a causative mechanism. The aim of this study was to investigate the cerebral metabolism of the important amino acids glutamate and glutamine in the db/db mouse model of T2DM. Glutamate and glutamine are both substrates for mitochondrial oxidation, and oxygen consumption was assessed in isolated brain mitochondria by Seahorse XFe96 analysis. In addition, acutely isolated cerebral cortical and hippocampal slices were incubated with [U-13C]glutamate and [U-13C]glutamine, and tissue extracts were analyzed by gas chromatography-mass spectrometry. The oxygen consumption rate using glutamate and glutamine as substrates was not different in isolated cerebral mitochondria of db/db mice compared to controls. Hippocampal slices of db/db mice exhibited significantly reduced 13C labeling in glutamate, glutamine, GABA, citrate, and aspartate from metabolism of [U-13C]glutamate. Additionally, reduced 13C labeling were observed in GABA, citrate, and aspartate from [U-13C]glutamine metabolism in hippocampal slices of db/db mice when compared to controls. None of these changes were observed in cerebral cortical slices. The results suggest specific hippocampal impairments in glutamate and glutamine metabolism, without affecting mitochondrial oxidation of these substrates, in the db/db mouse.


Thyroxine: effects of neonatal administration on maturation, development, and behavior.
In the report, "Thyroxine: effects of neonatal administration on maturation, development, and behavior," by S. Schapiro and R. J. Norman (10 Mar., p. 1279), the first line of Fig. 2 should read: "Fig. 2. Electroencephalograms from the cortex of thyroxine-treated and control infant...."


Protease inhibitor-containing regimens compared with nucleoside analogues alone in the suppression of persistent HIV-1 replication in lymphoid tissue.
Lymphoid tissue provides a reservoir where HIV can persist. However, therapies incorporating a protease inhibitor can target this reservoir. This study was designed to investigate the relative long-term effects on lymph-node viral load and cellular architecture of regimens containing multiple nucleosides alone or in combination with protease inhibitors. Axillary lymph-node biopsies from 12 patients with undetectable viraemia (viral load < 20 copies/ml: mean CD4 cells 525 x 10(6)/l) for a mean period of 25 months (range, 10-52 months) were investigated for the presence of HIV by in situ hybridization and coculture. Four patients were receiving multiple nucleoside analogues alone or in one case with a suboptimally dosed protease inhibitor (group I). Protease inhibitor was added to the regimen of seven patients at least 6 months prior to lymph-node biopsy (group II). Standard flow cytometry and virological data were obtained from peripheral blood every 3 months. By in situ hybridization, more productively infected CD4+ T cells were found in the lymph nodes of group I patients treated with nucleoside analogues alone. Very low numbers of productively infected lymph node cells were detected in the protease inhibitor-treated group II. No trapping of virions on the follicular dendritic cell (FDC) network was detectable in protease inhibitor-treated patients. In contrast, large deposits of FDC-bound virions were observed in three out of five patients from group I. Virus cultures from lymph node cells were positive in these three group I patients compared with only one out of seven patients from group II. Sequencing reverse transcriptase and protease genes from these isolates revealed typical mutations conferring resistance to the previously administered nucleoside analogue. A more preserved lymph node architecture and less signs of immunopathological change were also observed in protease inhibitor-treated patients. Undetectable plasma viraemia using the ultrasensitive PCR assay for prolonged periods of time does not always reflect complete HIV-1 suppression within the lymphoid compartment. Our results suggest that protease inhibitor-containing regimens target HIV reservoirs in lymphoid tissue more effectively and preserve or restore lymph node architecture.


Physical activity and immune function in elderly women.
The relationship between cardiorespiratory exercise, immune function, and upper respiratory tract infection (URTI) was studied in elderly women utilizing a randomized controlled experimental design with a follow-up of 12 wk. Thirty-two sedentary, elderly Caucasian women, 67-85 yr of age, who met specific selection criteria, were randomized to either a walking or calisthenic group; 30 completed the study. Twelve highly conditioned elderly women, 65-84 yr of age, who were active in endurance competitions, were recruited at baseline for cross-sectional comparisons. Intervention groups exercised 30-40 min, 5 d.wk-1, for 12 wk, with the walking group training at 60% heart rate reserve and the calisthenic group engaging in mild range-of-motion and flexibility movements that kept their heart rates close to resting levels. At baseline, the highly conditioned subjects exhibited superior NK (119 +/- 13 vs 77 +/- 8 lytic units, P < 0.01) and T (33.3 +/- 4.9 vs 21.4 +/- 2.1 cpm x 10(-3) using PHA, P < 0.05) cell function, despite no differences in circulating levels of lymphocyte subpopulations. Twelve weeks of moderate cardiorespiratory exercise improved the VO2max of the sedentary subjects 12.6%, but did not result in any improvement in NK cell activity or T cell function. Incidence of URTI was lowest in the highly conditioned group and highest in the calisthenic control group during the 12-wk study, with the walkers in an intermediate position (chi-square = 6.36, P = 0.042). In conclusion, the highly conditioned elderly women in this study had superior NK and T cell function when compared with their sedentary counterparts.(ABSTRACT TRUNCATED AT 250 WORDS)


Current trends in fibromyalgia research.
The development of standardised criteria for the diagnosis of fibromyalgia in 1990 has allowed careful study of this chronically painful syndrome. Epidemiological studies show increased symptoms and disability in patients with fibromyalgia, compared with other conditions associated with chronic, widespread pain. In addition, prevalence and severity of fibromyalgia symptoms are increased in women. Current studies have identified strong evidence for central sensitisation in fibromyalgia. Data from these studies may expand effective treatment options for fibromyalgia.


The clinical effectiveness and cost-effectiveness of second-eye cataract surgery: a systematic review and economic evaluation.
Elective cataract surgery is the most commonly performed surgical procedure in the NHS. In bilateral cataracts, the eye with greatest vision impairment from cataract is operated on first. First-eye surgery can improve vision and quality of life. However, it is unclear whether or not cataract surgery on the second eye provides enough incremental benefit to be considered clinically effective and cost-effective. To conduct a systematic review of clinical effectiveness and analysis of cost-effectiveness of second-eye cataract surgery in England and Wales, based on an economic model informed by systematic reviews of cost-effectiveness and quality of life. Twelve electronic bibliographic databases, including MEDLINE, EMBASE, Web of Science, The Cochrane Library and the Centre for Reviews and Dissemination databases were searched from database inception to April 2013, with searches updated in July 2013. Reference lists of relevant publications were also checked and experts consulted. Two reviewers independently screened references, extracted and checked data from the included studies and appraised their risk of bias. Based on the review of cost-effectiveness, a de novo economic model was developed to estimate the cost-effectiveness of second-eye surgery in bilateral cataract patients. The model is based on changes in quality of life following second-eye surgery and includes post-surgical complications. Three randomised controlled trials (RCTs) of clinical effectiveness, three studies of cost-effectiveness and 10 studies of health-related quality of life (HRQoL) met the inclusion criteria for the systematic reviews and, where possible, were used to inform the economic analysis. Heterogeneity of studies precluded meta-analyses, and instead data were synthesised narratively. The RCTs assessed visual acuity, contrast sensitivity, stereopsis and several measures of HRQoL. Improvements in binocular visual acuity and contrast sensitivity were small and unlikely to be of clinical significance, but stereopsis was improved to a clinically meaningful extent following second-eye surgery. Studies did not provide evidence that second-eye surgery significantly affected HRQoL, apart from an improvement in the mental health component of HRQoL in one RCT. In the model, second-eye surgery generated 0.68 incremental quality-adjusted life-years with an incremental cost-effectiveness ratio of £1964. Model results were most sensitive to changes in the utility gain associated with second-eye surgery, but otherwise robust to changes in parameter values. The probability that second-eye surgery is cost-effective at willingness-to-pay thresholds of £10,000 and £20,000 is 100%. Clinical effectiveness studies were all conducted more than 9 years ago. Patients had good vision pre surgery which may not represent all patients eligible for second-eye surgery. For some vision-related patient-reported outcomes and HRQoL measures, thresholds for determining important clinical effects are either unclear or have not been determined. Second-eye cataract surgery is generally cost-effective based on the best available data and under most assumptions. However, more up-to-date data are needed. A well-conducted RCT that reflects current populations and enables the estimation of health state utility values would be appropriate. Guidance is required on which vision-related, patient-reported outcomes are suitable for assessing effects of cataract surgery in the NHS and how these measures should be interpreted clinically. This project is registered as PROSPERO CRD42013004211. This project was funded by the National Institute for Health Research Health Technology Assessment programme.


An idea to explore: Engaging high school students in structure-function studies of bacterial sortase enzymes and inhibitors - A comprehensive computational experimental pipeline.
High school science fairs provide an exceptional opportunity for students to gain experience with scientific research, and participation has positive outcomes with respect to chosen careers in the sciences. However, it can be challenging to engage high school students in university-level research outside of formal internship programs. Here, we describe an experimental pipeline for a computational structural biology project that engages high school students. Students are involved at every step of the investigation and utilize freely available software to dock inhibitors onto protein homologues, and then analyze the resulting complexes. Bacterial sortases are transpeptidases on the cell surface of Gram-positive bacteria and are a potential target for the development of antibiotics. Students modeled inhibitors bound to sortases from several organisms, asking questions about affinity and selectivity. Their project was ranked in the top 10% at both regional and state science fairs. This project design is easily adaptable to countless other protein systems and provides a pipeline for collaborative high school student/university professor inquiry.


Comparison of store and forward method of teledermatology with face-to-face consultation.
To compare the accuracy of store and forward method of teledermatology with the traditional face-to-face consultation. The comparison was done between Institute of Dermatology King Edward Medical College Lahore that served as teledermatology center and Dermatology Department of Pakistan Institute of Medical Sciences Islamabad from where patients were selected. Telmedpak provided the technical support. Thirty three patients were selected from outpatient department of PIMS and images were taken using a digital camera. Images were stored in computer and were sent to Institute of Dermatology via e-mail for Teleconsultation along with a short history and examination findings. Diagnosis of consultant after face-to-face consultation was then compared with the image based diagnosis that is after teleconsultation. In 81% of the cases the diagnosis on face-to-face consultation was same (p < 0.05) while in 18% of the cases the two diagnoses differed. In 9% (n = 3) of the cases, image resolution was not good but out of these three, diagnosis was same in two and differed in one case. This study concludes that store and forward method of teledermatology is reliable and can provide a means of increasing access to dermatological care in rural and under-served areas.


Antibiofilm Activity of Polyamide 11 Modified with Thermally Stable Polymeric Biocide Polyhexamethylene Guanidine 2-Naphtalenesulfonate.
The choice of efficient antimicrobial additives for polyamide resins is very difficult because of their high processing temperatures of up to 300 °C. In this study, a new, thermally stable polymeric biocide, polyhexamethylene guanidine 2-naphtalenesulfonate (PHMG-NS), was synthesised. According to thermogravimetric analysis, PHMG-NS has a thermal degradation point of 357 °C, confirming its potential use in joint melt processing with polyamide resins. Polyamide 11 (PA-11) films containing 5, 7 and 10 wt% of PHMG-NS were prepared by compression molding and subsequently characterised by FTIR spectroscopy. The surface properties were evaluated both by contact angle, and contactless induction. The incorporation of 10 wt% of PHMG-NS into PA-11 films was found to increase the positive surface charge density by almost two orders of magnitude. PA-11/PHMG-NS composites were found to have a thermal decomposition point at about 400 °C. Mechanical testing showed no change of the tensile strength of polyamide films containing PHMG-NS up to 7 wt%. Antibiofilm activity against the opportunistic bacteria Staphylococcus aureus and Escherichia coli was demonstrated for films containing 7 or 10 wt% of PHMG-NS, through a local biocide effect possibly based on an influence on the bacterial eDNA. The biocide hardly leached from the PA-11 matrix into water, at a rate of less than 1% from its total content for 21 days.


Bifunctional silver(I) complex-catalyzed CO2 conversion at ambient conditions: synthesis of α-methylene cyclic carbonates and derivatives.
The chemical conversion of CO2 at atmospheric pressure and room temperature remains a great challenge. The triphenylphosphine complex of silver(I) carbonate was proved to be a robust bifunctional catalyst for the carboxylative cyclization of propargylic alcohols and CO2 at ambient conditions leading to the formation of α-methylene cyclic carbonates in excellent yields. The unprecedented performance of [(PPh3)2Ag]2CO3 is presumably attributed to the simultaneous activation of CO2 and propargylic alcohol. Moreover, the highly compatible basicity of the catalytic species allows propargylic alcohol to react with CO2 leading to key silver alkylcarbonate intermediates: the bulkier [(Ph3P)2Ag(I)](+) effectively activates the carbon-carbon triple bond and enhances O-nucleophilicity of the alkylcarbonic anion, thereby greatly promoting the intramolecular nucleophilic cyclization. Notably, this catalytic protocol also worked well for the reaction of propargylic alcohols, secondary amines, and CO2 (at atmospheric pressure) to afford β-oxopropylcarbamates.


[Optimization of extraction parameters and de-protein process for Gastrodia elata. Polysaccharides].
Grope for Optimization of Extraction Parameters and De-protein Process for Gastrodia elata Bl. Polysaccharides (GPS). Provide the theoretical basis for the industrialization production of GPS. The effects of extracting temperature, ration between Gastrodia elata Bl. and water, heating time on extraction rate of GPS were studied with orthogonal experimental design. Compared the application of the two de-protein process measures (Sevag and Enzyme-Sevag) in purification technics for Gastrodia elata Bl. The optimum parameters were: extraction 3h at 120 degrees C with 1:40 ratio of Gastrodia elata Bl. to water. The de-protein efficiency of Enzyme-Sevag is better than Sevag.


[Early Systolic Dysfunction of Left Ventricular Myocardium Is Reflected On Electrocardiogram of Patients With Aortic Stenosis].
to study relation between electrocardiographic (ECG) criteria of left ventricular hypertrophy (LVH) and parameters of tissue Doppler (TD) and LV strain in patients with aortic stenosis (AS) with preserved LV ejection fraction. We examined 80 patients with degenerative AS of all degrees of severity. Examination included history, blood serum cholesterol and creatinine, 12 lead ECG, routine echocardiography (EchoCG), TD, and LV global longitudinal peak strain (GLPS) in apical positions of 2-dimensional EchoCG. ECG criteria demonstrated low sensitivity relative to presence of real LVH. Average values of TD and (GLPS) were lowered in patients with AS. Correlation analysis revealed reverse relationship between TD and GLPX (<0.05). ROC-curve analysis showed very good quality of informativeness of the Cornell index and product for diagnosis of GLPX lowering below - 13%. ECG criteria of LVH poorly reflect real LVH but are markers of early systolic LV dysfunction.


Pathologists' acceptance of telepathology in the Ministry of National Guard Health Affairs Hospitals in Saudi Arabia: A survey study.
Evaluating users' attitudes and acceptance of telemedicine in the early phases of implementation is critical in predicting a successful adoption and utilization of the service. Telepathology does not require a patient's presence for intercommunication; therefore, it is essential to focus on the acceptance of the main occupational groups that are involved. This study aimed to assess the attitude and acceptance of telepathology in the pathology departments of the Ministry of National Guard Health Affairs (MNGHA) hospitals in Saudi Arabia. A cross-sectional survey was distributed among pathologists and laboratory technologists in the pathology departments of MNGHA hospitals (N = 78). The data collection instrument was built upon the technology acceptance model's (TAM's) constructs of perceived usefulness (PU), perceived ease of use (PEU), attitude (ATT), and intention to use (ITU). In total, 64 questionnaires were completed (response rate of 82%). The acceptance levels represented by the median responses to the TAM constructs, varied from 5.5 (slightly agree) to 6 (agree). The availability of digital pathology services in the workplace was significantly correlated with the participants' acceptance of telepathology. There was a strong correlation between ITU and PU and a moderate correlation between PEU and PU. Results suggest that telepathology is more likely to be adopted if it is considered helpful, therefore, it is recommended to focus on its usefulness and direct benefits during the training period. The participants who were familiar with the concept of digital pathology were more receptive to using telepathology, which might emphasize the importance of introducing and familiarizing the resident with digital health during their training period.


Improved methods for producing outer membrane vesicles in Gram-negative bacteria.
Outer membrane vesicle formation occurs during Gram-negative bacterial growth. However, natural production of large amounts of outer membrane vesicles has only been described in a few bacterial genera. The purified vesicles of some bacterial pathogens have shown potential applications in vaccinology and in antibiotic therapy. This study focused on the development of a gene expression system able to induce production of large amounts of outer membrane vesicles. The Tol-Pal system of Escherichia coli, required to maintain outer membrane integrity, is composed of five cell envelope proteins, TolA, TolB, TolQ, TolR and Pal. Tol proteins are parasitized by filamentous bacteriophages and by colicins. The phage infection process and colicin import require, respectively, the N-terminal domain of the minor coat g3p protein and the translocation domain of colicins, with both domains interacting with Tol proteins. In this study, we show that the periplasmic production of either Tol, g3p or colicin domains was able to specifically destabilize the E. coli or Shigella flexneri cell envelope and to induce production of high amounts of vesicles. This technique was further found to work efficiently in Salmonella enterica serovar Typhimurium.


Familial risk for major depression is associated with lower striatal 5-HT₄ receptor binding.
The 5-HT4 receptor provides a novel potential target for antidepressant treatment. No studies exist to elucidate the 5-HT4 receptor's in vivo distribution in the depressed state or in populations that may display trait markers for major depression disorder (MDD). The aim of this study was to determine whether familial risk for MDD is associated with cerebral 5-HT4 receptor binding as measured with [(11)C]SB207145 brain PET imaging. Familial risk is the most potent risk factor of MDD. We studied 57 healthy individuals (mean age 36 yrs, range 20-86; 21 women), 26 of which had first-degree relatives treated for MDD. We found that having a family history of MDD was associated with lower striatal 5-HT4 receptor binding (p = 0.038; in individuals below 40 years, p = 0.013). Further, we found evidence for a "risk-dose effect" on 5-HT4 receptor binding, since the number of first-degree relatives with a history of MDD binding correlated negatively with 5-HT4 receptor binding in both the striatum (p = 0.001) and limbic regions (p = 0.012). Our data suggest that the 5-HT4 receptor is involved in the neurobiological mechanism underlying familial risk for depression, and that lower striatal 5-HT4 receptor binding is associated with increased risk for developing MDD. The finding is intriguing considering that the 5-HT4 receptor has been suggested to be an effective target for antidepressant treatment.


Repeat liver resection after a hepatic or extended hepatic trisectionectomy for colorectal liver metastasis.
A right and left hepatic trisectionectomy and an extended trisectionectomy are the largest liver resections performed for malignancy. This report analyses a series of 23 patients who had at least one repeat resection after a hepatic trisectionectomy for colorectal liver metastasis (CRLM). A retrospective analysis of a single-centre prospective liver resection database from May 1996 to April 2009 was used for patient identification. Full notes, radiology and patient reviews were analysed for a variety of factors with respect to survival. Twenty-three patients underwent up to 3 repeat hepatic resections after 20 right and 3 left hepatic trisectionectomies. In 18 patients the initial surgery was an extended trisectionectomy. Overall 1-, 3- and 5-year survival rates after a repeat resection were 100%, 46% and 32%, respectively. No factors predictive for survival were identified. A repeat resection after a hepatic trisectionectomy for CRLM can offer extended survival and should be considered where appropriate.


A cross-sectional study of the ambulatory central artery stiffness index in patients with hypertension.
The present study aimed to investigate the characteristics of the ambulatory central artery stiffness index (AcASI) and its related factors. The association between AcASI and the left ventricular mass index (LVMI), and other factors related to atherosclerosis were explored.Patients with primary hypertension were enrolled into this study. Ambulatory central artery blood pressure (CABP) and ambulatory brachial artery blood pressure (BABP) were assessed using a Mobil-O-Graph NG hemomanometer, whereas AcASI and the ambulatory arterial stiffness index (AASI) were determined. LVMI was assessed by echocardiography.A total of 136 patients with primary hypertension were enrolled from May 2011 to January 2013 in Beijing Hospital. AcASI was significantly associated with AASI (r = 0.879, P < .001). AcASI was significantly lower than AASI (0.422 ± 0.302 vs 0.482 ± 0.270; P < .001). AcASI increased with age, ambulatory brachial mean blood pressure (MBP), and fasting glucose. AcASI was significantly associated with office pulse pressure (PP), ambulatory brachial PP, ambulatory central PP, and pulse wave velocity (PWV). AcASI, but not AASI, was significantly associated with LVMI. Receiver operator characteristic analysis indicated that AcASI and AASI could may be a predictor of left ventricular hypertrophy (LVH). Multiple regression analysis indicated that AcASI, chronic kidney disease, and hypertension course were associated with LVMI, but AASI was not.AcASI, which is obtained from ambulatory CABP monitoring, could be a new marker for the evaluation of atherosclerosis. AcASI may be stronger associated with LVH than AASI.


Seletracetam (ucb 44212) inhibits high-voltage-activated Ca2+ currents and intracellular Ca2+ increase in rat cortical neurons in vitro.
We analyzed the effects of seletracetam (ucb 44212; SEL), a new antiepileptic drug candidate, in an in vitro model of epileptic activity. The activity of SEL was compared to the effects of levetiracetam (LEV; Keppra), in the same assays. Combined electrophysiologic and microfluorometric recordings were performed from layer V pyramidal neurons in rat cortical slices to study the effects of SEL on the paroxysmal depolarization shifts (PDSs), and the simultaneous elevations of intracellular Ca(2+) concentration [Ca(2+)](i). Moreover, the involvement of high-voltage activated Ca(2+) currents (HVACCs) was investigated by means of patch-clamp recordings from acutely dissociated pyramidal neurons. SEL significantly reduced both the duration of PDSs (IC(50) = 241.0 +/- 21.7 nm) as well as the number of action potentials per PDS (IC(50) = 82.7 +/- 9.7 nm). In addition, SEL largely decreased the [Ca(2+)](i) rise accompanying PDSs (up to 75% of control values, IC(50) = 345.0 +/- 15.0 nm). Furthermore, SEL significantly reduced HVACCs in pyramidal neurons. This effect was mimicked by omega-conotoxin GVIA and, to a lesser extent, by omega-conotoxin MVIIC, blockers of N- and Q-type HVACC, respectively. The combination of these two toxins occluded the action of SEL, suggesting that N-type Ca(2+) channels, and partly Q-type subtypes are preferentially targeted. These results demonstrate a powerful inhibitory effect of SEL on epileptiform events in vitro. SEL showed a higher potency than LEV. The effective limitation of [Ca(2+)](i) influx might be relevant for its antiepileptic efficacy and, more broadly, for pathologic processes involving neuronal [Ca(2+)](i) overload.


High production of xanthan gum by a glycerol-tolerant strain Xanthomonas campestris WXLB-006.
The superior properties of xanthan gum make it an industrial aginomoto used in many industries, especially in oil recovery. In the present work, xanthan production from glycerol by a mutant strain Xanthomonas campestris WXLB-006 reached as high as 17.8 g/L in flask culture. With the adoption of pH control, varied aeration and agitation, and varied glycerol feeding strategy, xanthan production reached 33.9 g/L in a 7-L fermenter and fermentation time decreased to 60 hr. Instead of difficultly and costly purifying glycerol, this research provides a very good case for glycerol utilization. At the same time, this is the first report on a high glycerol-tolerant strain for microbial polysaccharide production and 33.9 g/L is the highest production of xanthan gum produced from glycerol so far.