Target-specific native/decoy pose classifier improves the accuracy of ligand ranking in the CSAR 2013 benchmark.
As part of the CSAR 2013 benchmark exercise, we have implemented a hybrid docking and scoring workflow to rank 10 steroid ligands of an engineered digoxigenin-binding protein. Schrödinger's Glide docking software was used to generate poses for each steroid ligand and rank them according to both standard docking precision (SP) and extra docking precision (XP) scoring functions. The unique component of our approach was the use of a target-specific pose classifier trained to discriminate nativelike from decoy poses. To build the classifier, a single cognate ligand with a known native pose (PDB code 4J8T) was docked multiple times into its target protein, and the generated poses were divided into two classes (nativelike and decoy) using a root-mean-square deviation threshold of 2 Å. All of the poses were characterized by the MCT-Tess descriptors of the protein-ligand interface, and random forest (RF) models were trained to discriminate the two classes of poses on the basis of their descriptors. The consensus pose classifier was then applied to the Glide-generated poses of each CSAR ligand in order to filter out those poses predicted as decoys and rerank the remaining ones using both XP and SP scoring functions. The best-scoring pose for each ligand following this filtering step was used for final ligand ranking. Overall, the ranking accuracy for the 10 ligands evaluated by the Spearman correlation coefficient was 0.64 for SP and 0.52 for XP but reached 0.75 for SP/RF consensus scoring (ranked third in the CSAR 2013 benchmark exercise). This study reconfirms that target-specific pose scoring models are capable of enhancing the reliability of structure-based molecular docking by discarding decoy poses.


Comparison of perioperative chemotherapy with adjuvant chemoradiotherapy for resectable gastric cancer: findings from a population-based study.
Both perioperative chemotherapy (PC) and adjuvant chemoradiotherapy (CRT) improve survival in resectable gastric cancer; however, these treatments have never been formally compared. Our objective was to evaluate treatment trends and compare survival outcomes for gastric cancer patients treated with surgery and either PC or CRT. We performed a retrospective population-based cohort study between 2007 through 2013 using California Cancer Registry data. Patients diagnosed with stage IB-III gastric adenocarcinoma and treated with total or partial gastrectomy were eligible for this study. Based on the type of treatment received, patients were grouped into surgery-only, PC, or CRT. Primary and secondary outcomes were overall survival (OS) and gastric cancer-specific survival (GCCS) respectively. Mortality hazards ratios (HRs) for each of these outcomes were computed using propensity score weighted and covariate-adjusted Cox regression models, stratified by clinical node status. Of 2,146 patients who underwent surgical resection, 1,067 had surgery-only, while 771 and 308 received PC or CRT, respectively. Median OS was 25, 33, and 52 months for surgery-only, PC, and CRT, respectively; P<0.001. Overall, patients treated with PC had significantly poorer survival compared to CRT (HR =1.45; 95% CI: 1.22-1.73). PC was also associated with higher mortality in patients with signet ring histology (HR =1.66; 95% CI: 1.21-2.28) and clinical node negative cancer (HR =1.85; 95% CI: 1.32-2.60). Survival was not different between PC vs. CRT in clinical node positive patients (HR =1.29; 95% CI: 0.84-2.08). Of note, the percentage of patients receiving PC increased from 17.5% in 2007-2008, to 41.5% in 2013-2014; P<0.001. Despite the rapid adoption of PC, overall, CRT is associated with better survival than PC. Specifically, clinical node negative and signet ring histology patients had better survival when treated with CRT compared to PC. Based on these findings, we recommend against indiscriminate adoption of PC and consideration for CRT over PC in clinical node negative patients.


Hand infections in Jamaica.
Empirical antibiotic treatment for hand infections is changing to single antibiotic therapy against Staphylococcus aureus in immunocompetent patients. Fifty-one patients treated surgically for hand infections were reviewed to assess the nature of infection in terms of site, organism, mechanism of injury, and antibiotic sensitivity of the organisms. Twenty-three per cent of patients had diabetes mellitus and were noted to be older than non-diabetics. Eighty-four per cent of non-diabetic patients had single organism infections, 59% involving S aureus. Fifty per cent of diabetic patients had multi-organism infection caused by gram positive and gram negative organisms. Patients stuck with a piece of wood also had multi-organism infections. Double antibiotic therapy is therefore advocated for patients with diabetes mellitus and all patients who had hand infections as a result of being stuck with a piece of wood. All others should have single antibiotic therapy with amoxycillin and clavulanic acid.


Electrocardiographic abnormalities and endocrine diseases--part a: hyperthyroidism.
Endocrine abnormalities can result in many different electrocardiographic abnormalities that can be confusing to the interpreting physician. Recognition and proper interpretation of these changes is helpful in the diagnosis, prognosis, and therapy of various endocrine diseases. Knowing these changes can help physicians avoid the diagnosis of myocardial ischemia, hypertrophy and arrhythmias in cases when the electrocardiographic changes are in reality because of disturbed endocrine function or the abnormal metabolic state.


Stimulation with estrogen and progesterone of luteinizing hormone (LH)-releasing hormone release from perifused adult female rat hypothalami: correlation with the LH surge.
The effects of estradiol benzoate (EB) and progesterone (P) in vivo and P in vitro on LHRH release from perifused preoptic area-medial basal hypothalamus (POA-MBH) tissue fragments were assessed. In the first series of experiments, ovariectomized female rats were given either 10 or 30 micrograms EB on day 0, followed by either oil or 5 mg P at 1000 h on day 2. Rats were killed at 2-h intervals after P or oil injection, and the POA-MBH from these rats were incubated in a perifusion system. LHRH release from the POA-MBH of rats primed with either 10 or 30 micrograms EB displayed similar patterns; from a basal rate at 1200 and 1400 h, LHRH secretion rose to significantly higher levels at 1600 and 1800 h. This increase in LHRH release in vitro was evident from the POA-MBH obtained just before and during the afternoon LH rise in vivo. On the other hand, the LHRH secretion pattern in vitro was different in two ways when rats were treated additionally with P. First, LHRH output was significantly higher at 1200 and 1400 h than that in rats treated with 10 or 30 micrograms EB only; this pattern was maintained later at 1600 and 1800 h from the POA-MBH of rats primed with 30 micrograms EB. Second, within the EB/P-treated (EBP) group, significant elevations in the LHRH output occurred from the POA-MBH obtained at 1800 h when rats were in the midst of the LH surge. In the other series of experiments, the POA-MBH of the EB-primed rats (30 micrograms/rat) were perifused with P (10 ng/ml) or vehicle for 6 h. The mean LHRH release during the 6-h interval was significantly higher after P perifusion; the bulk of this rise was evident at 4 h. These studies show that in vitro, the LHRH output of the POA-MBH from the EB- or EBP-treated rats varies significantly during the day and that the POA-MBH of EB-treated rats secretes large amounts of LHRH in vitro, which correlate well with the afternoon LH rise. In addition, treatment with P in vivo changes the in vitro pattern of LHRH output from the POA-MBH of these EB-primed rats, whereas superfusion of P in vitro induces only a marginal stimulation of LHRH release.


Pyogenic liver abscess: an improvement in prognosis.
Forty-six patients with pyogenic liver abscess have been treated at Paul Brousse Hospital between 1966 and 1986. The overall mortality was 24 per cent, all 11 deaths occurring in 24 patients seen prior to 1978 when there was often a considerable delay in the diagnosis of liver abscess (mean 90 +/- 71 days). In seven patients the diagnosis was not made until post-mortem examination. The mainstay of treatment was surgical drainage. Since 1978 high resolution imaging techniques for the liver, and in particular ultrasound, have been available. The diagnostic delay has been significantly reduced (mean 28 +/- 20 days, P less than 0.01). Patients are receiving definitive treatment at an earlier stage in the evolution of the disease process, with fewer established complications prior to treatment (P less than 0.05). Percutaneous drainage under ultrasound control is the preferred initial drainage procedure in high-risk patients. There have been no deaths in 22 patients treated for pyogenic liver abscess since 1978 (P less than 0.001).


[RISK FACTORS FOR POSTPARTUM OCCULT INJURIES OF THE ANAL SPHINCTER.]
introduction The overall risk of intrapartum damage the anal sphincter (IUAS) is 1% of all vaginal births. In contrast, the so-called "occult" anal sphincter injuries (OASIS) (defects esablished by endoanal ultrasonography) occur in 33% of primiparous women after vaginal birth. Identifying the most common risk factors for OASIS can be the basis for selecting high-risk patients. These women should be targeted by early pospartum diagnosis and treatment, which could reduce the incidence of anal incontinence developed later in life. Objectives To determine the role of common risk factors for the occurrence of OASIS in selected population. Material and methods The study included 42 patients after vaginal birth, born in Maternity Ljubljana in the period January to June 2009, and 38 patients from July 2009 to November 2011, born in Obstetric Clinic of the University Hospital - Pleven, diagnosed with OASIS using endoanal ultrasonography. Results We demonstrated that all of the independent variables studied in our research (primiparity, gestational age over 41gw and fetal weight over 3500 g.) are risk factors for the occurrence of OASIS. Discussion This sudy shows that the sudied risk factors for the occurrence of OASIS may be included in a clinical practice guideline for eady diagnosis and proper treatment of posTpartal injuries affecting the pelvic floor.


C-myc and tumour suppressor gene product expression in developing and term human trophoblast.
Proliferation and differentiation of villous trophoblast during placental development, from an early stage to full-term, were investigated in routinely fixed and processed tissues, by means of the immunocytochemical localization of the cell cycle-related proto-oncogene c-myc and the p53 and retinoblastoma susceptibility (Rb) tumour-suppressor gene products. The proliferative activity of the trophoblast was determined using an antibody against proliferating cell nuclear antigen (PCNA) which stains all proliferating cells in paraffin-embedded tissues. Diffuse nuclear immunoreactivity for PCNA, c-myc and Rb gene products was a consistent finding in early cytotrophoblast; c-myc product expression was also detectable in both layers of mid-gestation trophoblast. Only scattered cytotrophoblastic nuclei of early gestational placenta displayed immunostaining for p53 gene product. In full-term placenta c-myc expression was undetectable while Rb gene product and PCNA immunoreactivity declined markedly. These results indicate that the expression of the above genes is spatio-temporally regulated during placental development. A potential involvement of the oncosuppressor gene products p53 and Rb in the control of trophoblastic proliferation and of c-myc in the control of both the proliferative and differentiation pathways of trophoblastic cells is suggested.


The fertilization potential of donor semen between 1982 and 2004 in the industrial area of Upper Silesia (Poland).
The industrial area of Upper Silesia is the most polluted region in Poland. To assess if these conditions could influence male fertility, a retrospective analysis of the fertilization potential of donor semen was performed, taking as an outcome measure the pregnancy rate after donor inseminations in 1982-2004. Data on contamination of air and soil in the region were collected and compared with those of the rest of the country. In total 2,100 inseminations using fresh semen from 44 healthy donors with proven fertility in 1,617 cycles in 290 infertile couples were performed in 1982-1995 and 2,010 inseminations using frozen semen from 20 healthy donors with proven fertility in 1,994 cycles in 414 infertile couples were performed in 1996-2004. Significantly higher values of air and soil pollution compared to the rest of the country were stated. Pregnancies occurred in 125 patients inseminated by fresh semen and in 85 patients inseminated by frozen banked semen. The insemination efficiency was lower than expected and a distinct declining trend was observed in both groups. Significant rise in the number of cycles necessary for achieving pregnancy was noted. The fertilization potential of fresh and frozen donor semen in Upper Silesia is low and seems still to be diminishing. It might be speculated that this phenomenon could be caused by the high degree of industrial pollution.


Photochromic Inorganic/Organic Thermoplastic Elastomers.
Photochromic materials are an important class of "smart materials" and are broadly utilized in technological devices. However, most photochromic materials reported so far are composed of inorganic compounds that are challenging to process and suffer from poor mechanical performance, severely limiting their applications in various markets. In this paper, inorganic photochromic tungsten trioxide (WO3 ) nanocrystals are conveniently grafted with polymers to hurdle the deficiency in processability and mechanical properties. This new type of photochromic material can be thermally processed into desired geometries like disks and dog-bone specimens. Fully reversible photochromic response under UV light is also achieved for WO3 -graft polymers, exhibiting tunable response rate, outperforming the pristine WO3 nanocrystals. Notably, the resulted graft polymers show extraordinary mechanical performance with excellent ductility (≈800% breaking strain) and relatively high breaking strength (≈2 MPa). These discoveries elucidate an effective pathway to design smart inorganic/organic hybrid thermoplastic elastomers endowed with outstanding photochromic and mechanical properties as well as exceptional processability.


Familial aggregation of urinary tract and bone tumors: searching for a syndrome.
Positive family anamnesis is an important risk factor for cancer, and therefore further investigations need to be done if familial aggregation of cancer is observed. Due to a rare combination of urinary tract and bone tumors occurring in the family presented herein we hypothesized a hereditary predisposition and thus, Li-Fraumeni syndrome was considered to be the most likely differential diagnosis. To confirm Li-Fraumeni syndrome, we set out to investigate this case by analyzing the tumor suppressor gene p53. However, taking into account all the diagnostic results obtained, Li-Fraumeni syndrome could not be confirmed, but there is still uncertainty regarding a definitive diagnosis.


[Behavioral assessment of neuroleptics (1)--Active avoidance response].
The active avoidance responses in mice and/or rats are suppressed specifically by antipsychotic drugs at the doses which have no marked effect on the general behaviors and the other operant behaviors. In this respect the active avoidance responses have been applied for the preclinical evaluation of antipsychotic drugs. This paper describes accounting points for carrying out the active avoidance test, in particular continuous and discrete avoidance tasks of lever-press and shuttle types in mice and rats. Finally, the typical samples of the avoidance-suppressing effect of antipsychotic drugs (dopamine D2 antagonists) are presented.


Salvaging of adjacent fixed partial dentures using an overcasting technique.
Occasionally, clinicians are faced with a situation in which a solitary tooth between two bridges requires extraction. When this type of situation occurs, we must ponder the dilemma of how to replace the missing tooth. Options include placing an implant where the tooth was extracted or remaking one large multiunit bridge. Implants are not always possible or practical, and remaking a multiunit bridge that involves the abutments of the two existing bridges can be challenging and becomes much more expensive to the patients. The overcasting technique is a treatment modality that offers a solution in these particular situations.


[On the issue of paid-for medical services in state health care institutions].
The paid medical services are provided by public and municipal health care institutions. At that, legal relationships occurring in the process of paid provision of medical services are at the stage of development and their further progress depends on considerable amount of components of economical and legal forms. The article considers main problems related to functioning of medical institutions in the field of rendering paid medical services. The main legal documents regulating rendering of medical services on paid basis are analyzed too.


Identification of blood meals in Aedes aegypti by antibody sandwich enzyme-linked immunosorbent assay.
A comparative study of 3 ELISA protocols was performed for host blood meal identification in Aedes aegypti. In the sandwich-B ELISA, which used a combination of heavy and heavy+light chain conjugates, specificity was improved to such a degree that conjugates no longer required cross-adsorption with heterologous sera. Using the sandwich-B assay, human blood meals in laboratory reared Ae. aegypti could be detected longer after feeding (100% at 32 h and 80% at 42 h) than with a direct assay (100% at 20 h). Efficacy of the sandwich-B and direct ELISAs in field analyses was studied in parallel) using 80 field collected mosquitoes from Thailand. The sandwich-B assay was superior (88% detection rate) to the direct assay (41% detection rate) and was thus selected as the method of choice for future field studies.


Cercarial Dermatitis at Public Bathing Sites (Region Zealand, Denmark): A Case Series and Literature Review.
During recent years, we have observed an increasing occurrence of cercarial dermatitis in Denmark. We here describe 5 new cases from 2019 to 2020 associated with bathing in lakes Esrum sø, Furesø, and Ringen with emphasis on clinical symptoms and their relation to previous exposure to bird schistosome cercariae. In 2020, 2 patients from Furesø suffered from different severity of clinical symptoms after morning bathing in the same lake. We suggest that the differential symptoms may be explained by primary versus secondary exposure to the immunogenic pathogen.


Optimizing venetoclax dose in combination with low intensive therapies in elderly patients with newly diagnosed acute myeloid leukemia: An exposure-response analysis.
The objective of this research was to characterize the venetoclax exposure-efficacy and exposure-safety relationships and determine its optimal dose in elderly patients with newly diagnosed acute myeloid leukemia (AML) receiving venetoclax in combination with low intensity therapies (hypomethylating agent [HMA; azacitidine or decitabine] or low-dose cytarabine [LDAC]). A total of 212 patients from the HMA study and 92 patients from the LDAC study were included in the exposure-safety analyses. Those who received at least one dose of venetoclax and had at least one measurable response (201 and 83 in the HMA and LDAC studies, respectively) were included in the exposure-efficacy analyses. The probability of response based on International Working Group (IWG) for AML response criteria, adverse events of grade 3 or worse neutropenia or infection or a serious adverse event was modeled using logistic regression analyses to characterize the venetoclax exposure-response relationships. In combination with an HMA, increasing concentrations of venetoclax, up to those associated with a less than or equal to 400-mg once daily (QD) dose, were associated with a higher probability of response, with a trend for flat or decreasing probabilities of response thereafter. In combination with LDAC, increasing concentrations of venetoclax were associated with higher probabilities of response, with no plateau observed. Increasing concentrations of venetoclax were not associated with increasing probability of any safety event except for a slight increase in grade 3 or worse infections with HMAs; however, tolerability issues were observed at doses of greater than or equal to 800 mg QD in each study. Exposure-response analyses support the use of venetoclax 400 mg QD in combination with an HMA and 600 mg QD in combination with LDAC (ie, the next highest dose evaluated below 800 mg in each combination) to safely maximize the probability of response in elderly patients with newly diagnosed AML.


Ecologically relevant levels of multiple, common marine stressors suggest antagonistic effects.
Stressors associated with global change will be experienced simultaneously and may act synergistically, so attempts to estimate the capacity of marine systems to cope with global change requires a multi-stressor approach. Because recent evidence suggests that stressor effects can be context-dependent, estimates of how stressors are experienced in ecologically realistic settings will be particularly valuable. To enhance our understanding of the interplay between environmental effects and the impact of multiple stressors from both natural and anthropogenic sources, we conducted a field experiment. We explored the impact of multiple, functionally varied stressors from both natural and anthropogenic sources experienced during early life history in a common sessile marine invertebrate, Bugula neritina. Natural spatial environmental variation induced differences in conspecific densities, allowing us to test for density-driven context-dependence of stressor effects. We indeed found density-dependent effects. Under high conspecific density, individual survival increased, which offset part of the negative effects of experiencing stressors. Experiencing multiple stressors early in life history translated to a decreased survival in the field, albeit the effects were not as drastic as we expected: our results are congruent with antagonistic stressor effects. We speculate that when individual stressors are more subtle, stressor synergies become less common.


Evidence of eosinophil extracellular trap cell death in COPD: does it represent the trigger that switches on the disease?
In spite of the numerous studies on chronic obstructive pulmonary disease (COPD), the cellular and molecular basis of the disease's development remain unclear. Neutrophils and eosinophils are known to be key players in COPD. Recently, neutrophil extracellular trap cell death (NETosis), a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD. However, there is limited knowledge about eosinophil extracellular trap cell death (EETosis) and its role in the pathogenesis of COPD. The aim of this study was to evaluate EETosis in stable COPD. Induced sputum obtained from healthy smokers and low exacerbation risk COPD A or B group patients or high exacerbation risk COPD C or D group patients were included. Samples were examined using electron microscopy and immunofluorescence. Healthy smokers (n=10) and COPD A (n=19) group exhibited neutrophilic or paucigranulocytic phenotypes, with NETosis being absent in these patients. In contrast, COPD B (n=29), with eosinophilic or mixed phenotypes, showed EETosis and incipient NETosis. COPD C (n=18) and COPD D groups (n=13) were differentiated from low exacerbation rate-COPD group by the abundant cellular debris, with COPD C group having an eosinophilic pattern and numerous cells undergoing EETosis. A hallmark of this group was the abundant released membranes that often appeared phagocytosed by neutrophils, which coincidentally exhibited early NETosis changes. The COPD D group included patients with a neutrophilic or mixed pattern, with abundant neutrophil extracellular trap-derived material. This study is the first to demonstrate EETosis at different stages of stable COPD. The results suggest a role for eosinophils in COPD pathophysiology, especially at the beginning and during the persistence of the disease, regardless of whether the patient quit smoking, with EETosis debris probably triggering uncontrolled NETosis. The main target of these findings should be young smokers with the potential to develop COPD.


New insights into the clinical characteristics and prognostic factors of pulmonary fungal infections from a retrospective study in Southwestern China.
Despite increasing incidence of pulmonary fungal infections (PFIs) worldwide, the clinical characteristics and prognostic factors remain poorly understood. The goal of this study was to investigate the clinical features, laboratory findings, and outcomes of hospitalized patients diagnosed with PFIs. We retrospectively enrolled 123 patients at a university hospital in Southwestern China between February 2014 and May 2016, who were diagnosed with PFIs based on clinical presentations and laboratory tests including fungal culture and pathological examination. Medical records were reviewed and analyzed. Prognostic factor associated with mortality was evaluated by multivariate regression analysis. Of the 123 PFI patients enrolled, the mean age was 67 years with 72% of them being males. In addition to common clinical features reported previously, these patients exhibited distinct characteristics, with the elderly accounting for 79% of all cases, and with prolonged hospitalization being the most prevalent risk factor (74%) and chronic obstructive pulmonary disease (COPD) being the most common underlying disease (45%). Invasive operation was significantly more frequently involved in patients with unfavorable treatment responses than in patients with favorable responses (45.6 vs 7.4%, P=0.000). By multivariate regression analysis, invasive operation (odds ratio [OR]: 5.736, 95% confidence interval [CI]: 2.008-16.389, P=0.001) and hypoalbuminemia (OR: 3.936, 95% CI: 1.325-11.696, P=0.014) were independent prognostic factors of mortality in PFIs. This study provides new insights into the clinical characteristics and prognostic factors of PFIs and highlights the necessity to be aware of PFIs in patients with COPD and patients receiving invasive operation in order to improve clinical management of these patients.


Urinary concentrations of toxic and essential trace elements among rural residents in Hainan Island, China.
Toxic element exposure and essential trace element consumption may have changed after the Chinese economy transformed to a market-oriented system. The objectives of this study were to measure urinary concentrations of toxic (arsenic, cadmium, lead) and essential trace (selenium, zinc, copper) elements among rural residents in Hainan, China and to examine if variations in economic development are linked to differences in toxic and trace element exposure. We conducted a questionnaire-based survey and undertook anthropometric measurements of residents aged ≥20 years (n = 599). Urinary samples were collected and analyzed using inductively coupled plasma mass spectrometry. The median (μg/g creatinine) element concentrations were: arsenic, 73.2; cadmium, 1.8; lead, 3.1; selenium, 36.5; zinc, 371; and copper, 11.0. Intra-community variation in element concentrations was explained by age (arsenic, cadmium, zinc and copper), sex (arsenic, cadmium and selenium: higher in females; zinc: higher in males), body mass index (cadmium) and individual involvement in the market economy as indexed by agrochemical use (lead and selenium). The degree of community-level economic development, which was determined by the proportion of people living in better housing among the study communities, was positively associated with cadmium concentration. The degree of community-level economic development was positively associated with urinary cadmium concentration while individual involvement in the market economy was positively associated with lead and selenium.


[Mitotic activity in serous adenocarcinoma of the uterine body].
A comparative study of uterine serous (36) and endometrial (32) adenocarcinoma was undertaken. The former pathology revealed a higher mitotic index (18.2%) than the latter (11.4%) (p < 0.01). Predominance of metaphases among the variety of mitotic phases as well as high metaphase-prophase index (73.6% and 69.2% in serous and endometrial adenocarcinoma, respectively) were typical of malignant tumors in general. The share of patholological mitoses in serous adenocarcinomas was 1.6 times (61.8%) that in endometrial adenocarcinomas. Moreover, serous adenocarcinomas showed a wide range of pathological mitoses which were often responsible for aneuploidy development. The above differences in uterine serous and endometrial adenocarcinoma were in full conformity with the well known aggressive nature of the former pathology and may be used as an additional criterion of differential diagnosis.


Decreased beta-adrenoceptor-stimulated adenylyl cyclase activity in lymphocytes from Alzheimer's disease patients.
Previous studies have shown that in Alzheimer's disease post-mortem brain there are disruptions of both beta1-adrenoceptor-G-protein coupling and G-protein stimulation of adenylyl cyclase activity. Decreased beta-adrenoceptor stimulated adenylyl cyclase activity has also been shown in Alzheimer's disease primary skin fibroblasts. In the present study, we determined the regulation of adenylyl cyclase in Alzheimer's disease patients using an easily accessible tissue source, namely peripheral blood lymphocytes. beta-Adrenoceptor- and forskolin-stimulated adenylyl cyclase activities were investigated in lymphocytes from 12 Alzheimer's disease and 12 carefully matched and selected control subjects. No significant differences were found in basal or forskolin-stimulated enzyme activities between Alzheimer's disease and control lymphocytes. In contrast, isoprenaline-stimulated adenylyl cyclase activities were significantly lower in the Alzheimer's disease groups, as compared to controls. These results indicate that there is a widespread disruption of beta-adrenoceptor-G-protein-enzyme coupling in different tissues from Alzheimer's disease patients, and that adenylyl cyclase disturbances previously reported in Alzheimer's disease brain do not occur as a consequence of disease pathology or of terminal illness.


A novel wearable device for automated real-time detection of epileptic seizures.
Epilepsy is a neurological disorder that has a variety of origins. It is caused by hyperexcitability and an imbalance between excitation and inhibition, which results in seizures. The World Health Organization (WHO) and its partners have classified epilepsy as a major public health concern. Over 50 million individuals globally are affected by epilepsy which shows that the patient's family, social, educational, and vocational activities are severely limited if seizures are not controlled. Patients who suffer from epileptic seizures have emotional, behavioral, and neurological issues. Alerting systems using a wearable sensor are commonly used to detect epileptic seizures. However, most of the devices have no multimodal systems that increase sensitivity and lower the false discovery rate for screening and intervention of epileptic seizures. Therefore, the objective of this project was, to design and develop an efficient, economical, and automatically detecting epileptic seizure device in real-time. Our design incorporates different sensors to assess the patient's condition such as an accelerometer, pulsoxymeter and vibration sensor which process body movement, heart rate variability, oxygen denaturation, and jerky movement respectively. The algorithm for real-time detection of epileptic seizures is based on the following: acceleration increases to a higher value of 23.4 m/s2 or decreases to a lower value of 10 m/s2 as energy is absorbed by the body, the heart rate increases by 10 bpm from the normal heart rate, oxygen denaturation is below 90% and vibration should be out of the range of 3 Hz -17 Hz. Then, a pulsoxymeter device was used as a gold standard to compare the heart rate variability and oxygen saturation sensor readings. The accuracy of the accelerometer and vibration sensor was also tested by a fast-moving and vibrating normal person's hand. The prototype was built and subjected to different tests and iterations. The proposed device was tested for accuracy, cost-effectiveness and ease of use. An acceptable accuracy was achieved for the accelerometer, pulsoxymeter, and vibration sensor measurements, and the prototype was built only with a component cost of less than 40 USD excluding design, manufacturing, and other costs. The design is tested to see if it fits the design criteria; the results of the tests reveal that a large portion of the scientific procedures utilized in this study to identify epileptic seizures is effective. This project is objectively targeted to design a medical device with multimodal systems that enable us to accurately detect epileptic seizures by detecting symptoms commonly associated with an episode of epileptic seizure and notifying a caregiver for immediate assistance. The proposed device has a great impact on reducing epileptic seizer mortality, especially in low-resource settings where both expertise and treatment are scarce.


Extrafacial Melasma: A Scenario Less Explored.
Extrafacial melasma is a rare presentation, commonly occurring in postmenopausal women with a poor etiological insight and nature of its course. We planned to decipher the natural course of extrafacial melasma based on history questionnaire. Patients with diagnosis of extrafacial melasma were recruited. After informed consent, complete history including age of onset, duration, progression, sites of involvement (initial site as well as current site of pigmentation), treatment history, history of drug intake, family history, associated other diseases, and clinical photography and dermoscopy were done. Fifteen extrafacial melasma patients were recruited. All were females with mean age of 51.2 years. History of facial melasma in past was given by 93% of recruited patients. Mean total duration of melasma was 23 years. Ten (66%) patients had centrofacial melasma to begin with, 4 (26%) patients had malar melasma, and 1 (6.6%) had extrafacial melasma as initial presentation. Currently all patients had extrafacial melasma. Mean time for clearance of central face melasma was 18.2 years and appearance of melasma at extrafacial sites was 20 years. We infer that different clinical patterns of melasma occur sequentially over the natural course of disease and centrofacial melasma as the initial presentation in majority of our patients, progressed to involve extrafacial sites with time.


[Pre- and postpartum hemostasis in type II Willebrand-Jürgens syndrome].
In a female patient with a von Willebrand's disease type II (ristocetin cofactor less than 20%) shortly before and after birth of a son the factor VIII-related antigen and the ristocetin cofactor showed considerable increases, which some weeks later again decreased to the original values. Despite additional thrombocytopenia only on the 4th day post partum an easily controllable uterine haemorrhage was to be established. The risk of haemorrhage in von Willebrand's disease during pregnancy, birth and puerperium seems to be insignificant; nevertheless on the basis of the heterogeneity of this disease a peripartal coagulation-analytic control is regarded necessary.


CpG methylation inhibits proenkephalin gene expression and binding of the transcription factor AP-2.
DNA methylation at HpaII (CmCGG) sites inhibits expression of a human proenkephalin-CAT fusion gene when it is transiently expressed in CV-1 cells or stably expressed in C6-glioma cells. The inhibitory effects of HpaII methylation have been mapped to a site within the human proenkephalin promoter located at position -72 relative to the start site of transcription. This region spans a cAMP and phorbol ester inducible enhancer and methylation at this position inhibits both basal transcription and transcription induced by either cAMP or TPA. The HpaII site is located within an element which binds the transcription factor AP-2. In vitro methylation at this HpaII site inhibits the binding of AP-2. These results suggest that CpG methylation inhibits proenkephalin gene expression by directly interfering with the binding of a positively acting transcription factor previously shown to be essential for maximal basal, cAMP, and TPA inducible transcription.


High Prevalence of AH in HIV Patients on ART, in Bahia, Brazil.
The prevalence of arterial hypertension (AH) in HIV-patients is highly variable and its association with antiretroviral therapy (ART) is controversial. To estimate the prevalence of AH and associated factors in HIV-patients on ART. This cross-sectional study was conducted in HIV-patients attended in a referral center in Salvador, Brazil. We evaluated clinical, socio-demographic and anthropometric data. Student's ttests or Mann-Whitney's and Pearson's chi-square tests were used to compare the groups. Values of p <0.05 were considered significant. The variables that presented a value of p <0.20 were included in a logistic regression model. We evaluated 196 patients (60.7% male) with a mean age of 46.8 ± 11.7 years and a mean body mass index of 24.9 ± 5.3 kg / m2. The median elapsed time since HIV diagnosis and ART use was 11.8 (4.4 - 18.1) and 7.2 (2.7 - 15.3) years, respectively. The prevalence of AH was 41.8%. For individuals > 50 years old, there was a significant association between the increased abdominal circumference and AH and patients ≤ 50 years old presented significant association between AH and overweight, increased abdominal circumference and number of previous ART regimens. After multivariate analysis, age [OR:1.085; 95% CI 1,039 - 1,133], overweight [OR: 4.205; 95% CI 1,841 - 9,606], family history of AH [OR: 2.938; 95% CI 1,253 - 6.885], increased abdominal circumference [OR: 2.774; 95% CI 1.116 - 6.897] and life-time number of ART regimens used [OR: 3.842; 95% CI 1.307 - 11.299] remained associated with AH. AH was highly prevalent and was associated not only with classical risk factors for arterial hypertension, but also with specific ART regimens.


[Recent advances in directed evolution].
Screening is the bottleneck of directed evolution. In order to address this problem, a series of novel semi-rational designed strategies have been developed based on combinatorial active-site saturation test and iterative saturation mutagenesis, including single code saturation mutagenesis, double code saturation mutagenesis and triple code saturation mutagenesis. By creation of "small and smart" high qualified mutant libraries and combinatorial mutagenesis of specific sites, these new strategies have been successfully applied in multiparameter optimization, e.g. stereo/regioselectivity and activity. This review summarized recent advances in directed evolution and its applications in biocatalysis field.


Gating by tryptophan 73 exposes a cryptic pocket at the protein-binding interface of the oncogenic eIF4E protein.
Targeting protein-protein interacting sites for potential therapeutic applications is a challenge in the development of inhibitors, and this becomes more difficult when these interfaces are relatively planar, as in the eukaryotic translation initiation factor 4E (eIF4E) protein. eIF4E is an oncogene that is overexpressed in numerous forms of cancer, making it a prime target as a therapeutic molecule. We report here the presence of a cryptic pocket at the protein-binding interface of eIF4E, which opens transiently during molecular dynamics simulations of the protein in solvent water and is observed to be stable when solvent water is mixed with benzene molecules. This pocket can also be seen in the ensemble of structures available from the solution-state conformations of eIF4E. The accessibility of the pocket is gated by the side-chain transitions of an evolutionarily conserved tryptophan residue. It is found to be feasible for accommodating clusters of benzene molecules, which signify the plasticity and ligandability of the pocket. We also observe that the newly formed cavity provides a favorable binding environment for interaction of a well-recognized small molecule inhibitor of eIF4E. The occurrence of this transiently accessible cavity highlights the existence of a more pronounced binding groove in a region that has traditionally been considered to be planar. Together, the data suggest that an alternate binding cavity exists on eIF4E and could be exploited for the rational design and development of a new class of lead compounds against the protein.


[Isolation and characterization of Azotobacter sp. for the production of poly-beta-hydroxyalkanoates].
A microorganism (Azotobacter sp.) was isolated from soil samples from the Agronomy Faculty campus and its ability to accumulate poly-beta-hydroxyalkanoate (PHAs) polymers was analyzed. The isolated strain (named No 8) accumulated 8 micrograms PHA/m of culture media as intracytoplasmic granules. The following properties of the strain were analyzed: utilization of different carbon sources, antibiotic resistance, optimal pH and temperature, pigment production, nitrogen fixation, proteolytic activity, acid and hydrogen sulphide production, optimal growth temperature, cyst formation, growth on phenol and sodium fluoride, catalase, pleomorfism and mobility. The synthesized polymer showed valuable properties respect to organic solvents resistance.


Thoughts about conceptual models of nursing and health policies.
In this essay, we present a conceptual framework for analysis and evaluation of sexuality education health policies based on the conceptual model of nursing and health policy and the Neuman systems model. The framework is intended to facilitate understanding of sexuality education policies promulgated by the governments of any country in the world.


Exanthematic type of pustular psoriasis consisting of two types of pustular lesion.
A 35-year-old female developed generalized pustules within a short period of time. Clinically, two distinct types of pustules were observed, viz. erythematous patches studded with crops of small pustules, and isolated large pustules with a red halo. Histologically, the former were subcorneal spongiform pustules, whereas the latter were unilocular pustules involving the hair follicular infundibulum or a subcorneal unilocular pustule on the palmo-plantar skin. On the basis of the sudden appearance of the pustules without any pre-existing lesions of psoriasis and the histological findings of the spongiform pustules, we made a diagnosis of the exanthematic type of pustular psoriasis. The lesions responded in a dose-dependent fashion to oral cyclosporin.


Increased urinary exosomal SYT17 levels in chronic active antibody-mediated rejection after kidney transplantation via the IL-6 amplifier.
Chronic active antibody-mediated rejection (CAAMR) is a particular problem in kidney transplantation (KTx), and ~25% of grafts are lost by CAAMR. Further, the pathogenesis remains unclear, and there is no effective cure or marker. We previously found that a hyper NFκB-activating mechanism in non-immune cells, called the IL-6 amplifier, is induced by the co-activation of NFκB and STAT3, and that this activation can develop various chronic inflammatory diseases. Here, we show that synaptotagmin-17 (SYT17) is increased in an exosomal fraction of the urine from CAAMR patients, and that this increase is associated with activation of the IL-6 amplifier. Immunohistochemistry showed that SYT17 protein expression was increased in renal tubule cells of the CAAMR group. While SYT17 protein was not detectable in whole-urine samples by western blotting, urinary exosomal SYT17 levels were significantly elevated in the CAAMR group compared to three other histology groups (normal, interstitial fibrosis and tubular atrophy, and calcineurin inhibitors toxicity) after KTx. On the other hand, current clinical laboratory data could not differentiate the CAAMR group from these groups. These data suggest that urinary exosomal SYT17 is a potential diagnostic marker for CAAMR.


Response of human immunodeficiency virus-infected adults to measles-rubella vaccination.
Measles-mumps-rubella vaccine (MMR) is recommended for human immunodeficiency virus-infected (HIV+) adults. Data concerning MMR vaccination of HIV+ patients are limited to children. We evaluated 39 HIV+ (97% with > 200 CD4+ lymphocytes) and 17 non-HIV+ control adults receiving measles-rubella vaccine (MR). Clinical adverse events did not differ between groups. Prevaccination, three HIV+ and two control vaccinees were measles seronegative; no HIV+ and one control vaccinee seroconverted. No initially measles-seropositive vaccinee had a significant antibody elevation. Four HIV+ and three control vaccinees were rubella seronegative prevaccination; three HIV+ and two control vaccinees seroconverted. Among those initially rubella seropositive, two HIV+ and one control vaccinee had significant antibody elevations. There were no significant percentage CD4+ or CD8+ lymphocyte changes between groups. Three HIV+ vaccinees were p24 antigen positive pre- and postvaccination. Although MR vaccination appears safe in HIV+ adults, questions remain about the response of measles and rubella antibody-negative HIV+ adults and those with < 200 CD4+ lymphocytes.


Comparison of transillumination and histologic slide measurements of tumor diameter in uveal melanoma.
Tumor size is an important prognostic factor for deaths due to uveal melanoma. The objectives of this study are: (1) to determine the association between largest tumor diameter assessed by clinical transillumination and largest tumor diameter assessed by measurement of the histologic slide; (2) to predict a clinical transillumination diameter for each enucleation specimen based on the best combination of histologic variables--diameter, height, location, and tumor shape; and (3) to use the predicted transillumination diameter in place of histologic diameter measurement as a prognostic factor for patients treated by enucleation in order to reevaluate previously reported survival outcomes for patients treated by proton beam and enucleation. Comparison of measurements on 40 eyes indicated that transillumination largest diameter measurements were larger than histologic slide measurements (mean difference, 2.87 mm). Multiple linear regression analysis yielded the following equation: transillumination diameter = [4.73 + (0.58 X histologic diameter) + (0.38 X histologic height) + (1.87 X anterior location)]. Using the actual and predicted transillumination measurements, the results of this study support a previously published report on these data: treatment type, tumor size, and location were predictive of melanoma-related deaths, metastases, and all deaths.


One health approach on serosurvey of anti-Leptospira spp. in homeless persons and their dogs in South Brazil.
Although leptospirosis has been described as a worldwide bacterial zoonosis primarily affecting vulnerable populations, to date no study has focused on concomitant serosurvey of homeless persons and their dogs. The aim of the present study was, to use a One Health approach to serologically assess homeless persons and their dogs in 3 major cities of south Brazil (São Paulo, Curitiba, and Foz do Iguaçu). Environmental information was obtained with an epidemiological questionnaire given to all participants. A total of 200 human and 75 dog samples were tested for anti-Leptospira spp. antibodies to thirty different serovars using the microscopic agglutination test. None of the homeless persons were positive while 5 of the 75 (6.7%) dogs were positive. Among homeless population, 89% (177 of 200) were male, 61% (122 of 200) self-declared Non-white, and 67% (134 of 200) were educated up to the 8th school grade. Lower exposure of homeless persons to Leptospira spp. in the present study when compared to other vulnerable populations (slum and low-income residents) may be result of less direct exposure as they are able to rapidly change locations in response to flooding events. In addition, these results may reflect the effectiveness of a specific healthcare service provided to people living in the streets in the 3 cities. While dogs may be used as environmental sentinels for leptospirosis, the low seropositivity results found in this report may indicate low transmission risk to homeless owners in direct daily contact with their dogs.


Stimulation of the lambda pR promoter by Escherichia coli SeqA protein requires downstream GATC sequences and involves late stages of transcription initiation.
Escherichia coli SeqA protein is a major negative regulator of chromosomal DNA replication acting by sequestration, and thus inactivation, of newly formed oriC regions. However, other activities of this protein have been discovered recently, one of which is regulation of transcription. SeqA has been demonstrated to be a specific transcription factor acting at bacteriophage lambda promoters p(I), p(aQ) and p(R). While SeqA-mediated stimulation of p(I) and p(aQ) occurs by facilitating functions of another transcription activator protein, cII, a mechanism for stimulation of p(R) remains largely unknown. Here, it has been demonstrated that two GATC sequences, located 82 and 105 bp downstream of the p(R) transcription start site, are necessary for this stimulation both in vivo and in vitro. SeqA-mediated activation of p(R) was as effective on a linear DNA template as on a supercoiled one, indicating that alterations in DNA topology are not likely to facilitate the SeqA effect. In vitro transcription analysis demonstrated that the most important regulatory effect of SeqA in p(R) transcription occurs after open complex formation, namely during promoter clearance. SeqA did not influence the appearance and level of abortive transcripts or the pausing during transcription elongation. Interestingly, SeqA is one of few known prokaryotic transcription factors which bind downstream of the regulated promoter and still act as transcription activators.


Comparison of Segger and other methods for segmentation and rigid-body docking of molecular components in cryo-EM density maps.
Segmentation and docking are useful methods for the discovery of molecular components in electron cryo-microscopy (cryo-EM) density maps of macromolecular complexes. In this article, we describe the segmentation and docking methods implemented in Segger. For 11 targets posted in the 2010 cryo-EM challenge, we segmented the regions corresponding to individual molecular components using Segger. We then used the segmented regions to guide rigid-body docking of individual components. Docking results were evaluated by comparing the docked components with published structures, and by calculation of several scores, such as atom inclusion, density occupancy, and geometry clash. The accuracy of the component segmentation using Segger and other methods was assessed by comparing segmented regions with docked components.


Clinical, biochemical, and genetic analysis of the mitochondrial respiratory chain complex I deficiency.
Mitochondrial respiratory chain complex I deficiency is one of common mitochondrial disorders. However, the information is relatively little about the features of Chinese patients. In this study, the clinical, biological, and genetic analyses were performed in the children with respiratory chain complex I deficiency, in order to further understand the characteristics of the disease.Over a 3-year period, 67 patients (37 boys, 30 girls), presenting with unexplained multisystemic symptoms and signs were recruited. Clinical and laboratory data of the patients were summarized. Spectrophotometric assay was used for the analysis of mitochondrial complex I-V enzyme activity in peripheral leukocytes. The entire mitochondrial DNA (mtDNA) sequence was analysed for patients and their mothers.The children with respiratory chain complex I deficiency presented with multisystem dysfunction. Onset occurred before the third year of life in 96.9% patients without mtDNA mutation. Onset occurred before the third year of life in 76.5% of patients with mtDNA mutation (P = .03). About 51.5% of patients without mtDNA mutation had weakness, which is higher than 24% patients with mtDNA mutation (P = .02). Isolated complex I deficiency and combined complex I deficiency were found in 45 and 22 patients, respectively. The prevalence of isolated complex I deficiency was higher in the patients with mtDNA mutations (79.4%) than in the patients without mtDNA mutations (54.5%).Patients with nuclear DNA mutations are more likely to develop early onset in mitochondrial respiratory chain complex I deficiency. The patients with complex I deficiency of peripheral leukocytes may be more likely to be caused by mtDNA mutation.


Thermal imaging and dermoscopy for detecting inflammation in frontal fibrosing alopecia.
Frontal fibrosing alopecia (FFA) is an inflammatory condition of the scalp, which leads to scarring and slowly progressive recession of frontotemporal and/or frontoparietal hairline. Choice of FFA treatment is highly dependent on accurate assessment of disease phase, as medical treatments are effective only during the initial inflammatory stage. To objectively quantify the activity of the inflammatory process in FFA, 22 female patients were examined by both infrared thermography and optical dermoscopy before tissue sampling. The presence of perifollicular erythema or scaling was considered to be strongly suggestive for appropriate scalp biopsy site. Skin temperature differences in dermoscopy-selected area >0.5°C for temperature of the reference area (lower area of forehead) were considered abnormal. For evaluation of the inflammatory infiltrate, a grading scale was used. The scale classified 14 (64%) subjects as being in the active disease phase of FFA and eight (36%) as in the inactive one. Using the thermography findings, 17 (77%) patients were considered to have the active FFA and five (23%) patients had the inactive one. The clinical assessment of active FFA was most accurate using thermal imaging combined with dermoscopy, with a sensitivity of 64%, a specificity of 88%, a positive predictive value of 90%, and an negative predictive value of 58%. We believe that infrared thermography is a noninvasive and accessible imaging modality that may serve as a complementary tool in FFA diagnosis.


Microbial monitoring of ammonia removal in a UASB reactor treating pre-digested chicken manure with anaerobic granular inoculum.
Performance and microbial community dynamics in an upflow anaerobic sludge bed (UASB) reactor coupled with anaerobic ammonium oxidizing (Anammox) treating diluted chicken manure digestate (Total ammonia nitrogen; TAN=123±10mg/L) were investigated for a 120-d operating period in the presence of anaerobic granular inoculum. Maximum TAN removal efficiency reached to above 80% with as low as 20mg/L TAN concentrations in the effluent. Moreover, total COD (tCOD) with 807±215mg/L in the influent was removed by 60-80%. High-throughput sequencing revealed that Proteobacteria, Actinobacteria, and Firmicutes were dominant phyla followed by Euryarchaeota and Bacteroidetes. The relative abundance of Planctomycetes significantly increased from 4% to 8-9% during the late days of the operation with decreased tCOD concentration, which indicated a more optimum condition to favor ammonia removal through anammox route. There was also significant association between the hzsA gene and ammonia removal in the UASB reactor.


The Revolving Door Flap: Revisiting an Elegant but Forgotten Flap for Ear Defect Reconstruction.
Background The revolving door flap, although well described in the literature, is not widely used in general plastic surgery practice. The flap has been used for anterior auricular and conchal defects and is considered elegant for its unique flap design and peculiarity of flap harvest. However, due to its use for a very specific purpose and unique flap harvest technique that may be difficult to grasp, the flap is not very popular in reconstructive practice. Objectives This study aims to evaluate the understanding and learning curve of the revolving door flap, assess surgical outcome, and reemphasize its utility and elegance in reconstruction of ear defects. Methodology This is a case series of nine surgeries performed between January 2014 and 2018. Three cases were performed by the senior author and six cases by two junior authors. Patients were observed for complications and aesthetic outcomes. Results The mean dimension of the flaps was 27.22 mm × 22.78 mm. The mean operative time was 56.56 minutes (standard deviation 22.50, standard error of the mean 7.5). Flap congestion was noted in three cases postoperatively which resolved completely by the second week. Major "pinning" of the ear was noted in four cases. Conclusion Though infrequently performed, the revolving door flap has an easy learning curve once the proper harvest technique and flap movement has been grasped. The flap harvest is convenient, safe, and yields predictable results. Not only is total or partial flap loss extremely rare, the flap is sensate, color match is good, auricular contour is maintained, and the donor site can be closed primarily and remains well hidden.


Neothioviridamide, a Polythioamide Compound Produced by Heterologous Expression of a Streptomyces sp. Cryptic RiPP Biosynthetic Gene Cluster.
During genome mining for thioviridamide-like biosynthetic gene clusters that could produce polythioamide RiPP (ribosomally synthesized and post-translationally modified peptides), we discovered a novel cryptic biosynthetic gene cluster. During efforts to express this biosynthetic gene using heterologous expression of this biosynthetic gene cluster, a novel compound designated as neothioviridamide was produced. We report herein the cloning and heterologous expression of the neothioviridamide biosynthetic gene cluster and the isolation, structure determination, and cytotoxic activity of neothioviridamide.


Tzeananiaceae, a new pleosporalean family associated with Ophiocordycepsmacroacicularis fruiting bodies in Taiwan.
The order Pleosporales comprises a miscellaneous group of fungi and is considered to be the largest order of the class Dothideomycetes. The circumscription of Pleosporales has undergone numerous changes in recent years due to the addition of large numbers of families reported from various habitats and with a large amount of morphological variation. Many asexual genera have been reported in Pleosporales and can be either hyphomycetes or coelomycetes. Phoma-like taxa are common and have been shown to be polyphyletic within the order and allied with several sexual genera. During the exploration of biodiversity of pleosporalean fungi in Taiwan, a fungal strain was isolated from mycelium growing on the fruiting body of an Ophiocordyceps species. Fruiting structures that developed on PDA were morphologically similar to Phoma and its relatives in having pycnidial conidiomata with hyaline conidia. The fungus is characterised by holoblastic, cylindrical, aseptate conidiogenous cells and cylindrical, hyaline, aseptate, guttulated, thin-walled conidia. Phylogenetic analysis based on six genes, ITS, LSU, rpb2, SSU, tef1 and tub2, produced a phylogenetic tree with the newly generated sequences grouping in a distinct clade separate from all of the known families. Therefore, a new pleosporalean family Tzeananiaceae is established to accommodate the monotypic genus Tzeanania and the species T.taiwanensis in Pleosporales, Dothideomycetes. The Ophiocordyceps species was identified as O.macroacicularis and this is a new record in Taiwan.


Cardiac resynchronization therapy after atrioventricular junction ablation for symptomatic atrial fibrillation: a meta-analysis.
Atrioventricular junction (AVJ) ablation with permanent pacing improves symptoms in selected patients with atrial fibrillation (AF). The optimal pacing modality after AVJ ablation remains unclear. We performed a meta-analysis of randomized controlled trials to examine whether cardiac resynchronization therapy (CRT) is superior to right ventricular (RV) pacing in this patient population. We searched the MEDLINE and EMBASE databases for studies evaluating the effect of CRT vs. RV pacing after AVJ ablation for AF. Pooled risk ratios (RRs) and mean differences with 95% confidence intervals (CIs) were calculated for categorical and continuous outcomes, respectively, using a random effects model. Five trials involving 686 patients (413 in CRT and 273 in RV pacing group) were included in the analysis. On the basis of the pooled estimate across the studies, CRT resulted in a non-significant reduction in mortality (RR = 0.75, 95% CI 0.43-1.30; P= 0.30) and a significant reduction in hospitalizations for heart failure (RR = 0.38, 95% CI = 0.17-0.85; P= 0.02) compared with RV pacing. Cardiac resynchronization therapy did not improve 6 min walk distance (mean difference 15.7, 95% CI -7.2 to 38.5 m; P= 0.18) and Minnesota Living with Heart Failure quality-of-life score (mean difference -3.0, 95% CI -8.6 to 2.6; P= 0.30) compared with RV pacing. The change in left ventricular ejection fraction between baseline and 6 months favoured CRT (mean change 2.0%, 95% CI 1.5-2.4%; P< 0.001). Cardiac resynchronization therapy may be superior to RV pacing in patients undergoing AVJ ablation for AF. Further studies, adequately powered to detect clinical outcomes, are required.


An unusual inguinoscrotal hernia with renal involvement.
We present a case of a 74-year-old man who, while in intensive treatment unit for an upper gastrointestinal bleed, decompensated cardiac failure and concurrent pneumonia, was found to have a large right hydronephrotic pelvic kidney and bladder within the hernia. After discharge, he was medically optimised for 7 months before undergoing an elective open mesh repair of his hernia. During the procedure, drainage of a large hydrocoele was performed to facilitate reduction of the hernia. Postoperatively, he underwent ureteric stenting due to a persistent hydronephrosis with impairment of his renal function. He subsequently made a good recovery and was discharged home with outpatient follow-up planned.


Visualization of Actin Cytoskeleton in Cellular Protrusions in Medaka Embryos.
Cellular protrusions are fundamental structures for a wide variety of cellular behaviors, such as cell migration, cell-cell interaction, and signal reception. Visualization of cellular protrusions in living cells can be achieved by labeling of cytoskeletal actin with genetically encoded fluorescent probes. Here, we describe a detailed experimental procedure to visualize cellular protrusions in medaka embryos, which consists of the following steps: preparation of Actin-Chromobody-GFP and α-bungarotoxin mRNAs for actin labeling and immobilization of the embryo, respectively; microinjection of the mRNAs into embryos in a mosaic fashion to sparsely label individual cells; removal of the hard chorion, which hampers observation; and visualization of cellular protrusions in the embryo with a confocal microscope. Overall, our protocol provides a simple method to reveal cellular protrusions in vivo by confocal microscopy.


Dimensional approaches to experimental psychopathology of schizophrenia: shift learning and report of psychotic-like experiences in college students.
Adopting a dimensional approach to experimental psychopathology, and taking into account inconsistencies in the previous literature, we examined whether reports of psychotic-like experiences in undergraduate students were associated with shift-learning deficits, akin to those seen in schizophrenia. The participants (N=72) were tested on a new compound stimulus discrimination task before and after a target shift, and were administered a multi-dimensional schizotypy inventory (O-LIFE). Performance impairment following a target shift was associated with the negative (introvertive anhedonia) and the impulsive (impulsive non-conformity) dimension of schizotypy, but not with the positive (unusual experiences), nor the disorganised (cognitive disorganisation) dimension. None of the schizotypy measures were associated with performance on discrimination learning before the target shift. The obtained results are in line with past evidence that shift learning is associated with the severity of the negative symptomatology of schizophrenia. The possibility that psychotic-like features may contribute differentially to performance deficits across successive stages of learning is considered.


Ultrasound assessment of cervical status compared to the Bishop score - predicting the success of labor induction using a machine learning-based model.
The main aim of this study was to develop a machine-learning-based model for predicting the success of labor induction (IOL). To that end, the clinical and ultrasound parameters that affect the successfulness of labor induction were assessed. Then, a new ultrasound scoring system (USS) was developed and assessed. This prospective observational study included 192 term women who underwent induction of labor. First, a wide range of clinical and ultrasound pre-induction parameters were recorded. The induction was initiated by endocervical administration of dinoprostone gel (for Bishop score ≤5) or intravenous oxytocin (for Bishop score ≥6). After evaluating ultrasound parameters, we created an ultrasound scoring system and compared it with the Bishop score and clinical parameters. Finally, a comprehensive model using machine learning algorithms for predicting the success of the induction of labor was developed. In terms of clinical parameters, this study found that IOL correlates with parity, body mass index (BMI) (both at p<0.05), and the Bishop score (p<0.001). All ultrasound parameters were statistically significant (p<0.05) apart from the posterior cervical angle. However, compared to the Bishop score, the new USS showed a slightly lower sensitivity (0.55 compared to 0.64) but much higher specificity (0.75 compared to 0.44) at a cut-off of 1.66. The proposed model, which can predict 83% of the events correctly, encompasses the Bishop score, USS, and clinical parameters. The findings imply that the model developed in this study, which takes into account clinical parameters (parity, BMI), the ultrasound parameters and the Bishop score and uses machine learning algorithms, yields better results than models using other parameters.


[Results of cyclosporin A therapy in the early phase of type I diabetes mellitus].
A number of findings concerning the pathogenesis of insulin-dependent diabetes mellitus have shown that an autoimmune process is responsible for the destruction of the beta-cell mass, and that a major part of this process has already occurred during the prediabetic phase of the disease. Various immunosuppressive intervention trials have, thus, recently been performed. Remission rates of between 30% and 50% in the Canadian cyclosporin A (CyA) pilot study prompted two placebo-controlled double-blind studies applying this medication. In the French CyA trial 122 patients were followed up for 9 months. 37% of those on high-dose CyA (whole blood levels greater than 300 ng/ml) achieved total remission, compared with 16.7% of those on low-dose CyA (blood level less than 300 ng/ml) and 5% of the placebo group. The Canadian-European trial included 188 patients, of whom 42 were treated in the Viennese centre. Diabetes had been diagnosed in these 42 patients not more than 6 weeks previously, and the duration of their symptoms did not exceed 14 weeks. Whole blood CyA levels ranged from 400 to 800 ng/ml. In relation to short duration of symptoms and early commencement of treatment up to 10 times higher total remission rates were found in the CyA group as compared with the placebo group. In both studies similar side effects were seen. Apart from the cosmetic side effects (hypertrichosis, gingival hyperplasia) a decrease of 20% in creatinine clearance and an increase of 20% in plasma creatinine level seemed to be of clinical importance.(ABSTRACT TRUNCATED AT 250 WORDS)


Mortality in Rheumatoid Arthritis (RA): factors associated with recording RA on death certificates.
Death certificates can be used to assess disease prevalence and incidence; however, rheumatoid arthritis (RA) often remains unreported in death certificates. We sought to determine to what extent RA is underreported and what demographic and clinical characteristics could predict mention of RA in the death certificate. We recruited 1328 patients with RA from private, public and military rheumatology practices and followed them prospectively for yearly evaluations. A rheumatologist assessed clinical characteristics of RA and comorbidities at each evaluation. Deaths were identified through family members, other physicians, obituaries and public death databases. All were confirmed with state-issued death certificates. Patients with and without RA in death certificate were compared using bivariate and multivariate analyses. By December 2013, 326 deaths had occurred. We received and reviewed death certificates for all confirmed deaths, of which 58 (17.7 %) mentioned RA on the death certificate. Bivariate analysis revealed that younger age, a greater number of deformities, higher Sharp score and lower socioeconomic status were each associated with recording RA. Multivariable analyses revealed that comorbidity [OR (95 % CI) = 0.84 (0.73, 0.97); P = 0.022] was inversely associated with listing RA on the death certificate, while the number of deformities [OR (95 % CI) = 1.04 (1.00, 1.07); P = 0.033] and a certified physician's signature on the death certificate [OR (95 % CI) = 4.79 (1.35, 16.9); P = 0.015] increased likelihood of reporting RA. In this cohort, RA was not listed in over 80 % of death certificates. Younger patients with fewer comorbidities and more joint deformities were more likely to have RA reported. RA is often not included in death certificates. The findings of this study suggest that older patients may have a greater number of comorbidities, thus decreasing the likelihood that RA be included when completing the death certificate.


Chemical modifications of Au/SiO2 template substrates for patterned biofunctional surfaces.
The aim of this work was to create patterned surfaces for localized and specific biochemical recognition. For this purpose, we have developed a protocol for orthogonal and material-selective surface modifications of microfabricated patterned surfaces composed of SiO(2) areas (100 μm diameter) surrounded by Au. The SiO(2) spots were chemically modified by a sequence of reactions (silanization using an amine-terminated silane (APTES), followed by amine coupling of a biotin analogue and biospecific recognition) to achieve efficient immobilization of streptavidin in a functional form. The surrounding Au was rendered inert to protein adsorption by modification by HS(CH(2))(10)CONH(CH(2))(2)(OCH(2)CH(2))(7)OH (thiol-OEG). The surface modification protocol was developed by testing separately homogeneous SiO(2) and Au surfaces, to obtain the two following results: (i) SiO(2) surfaces which allowed the grafting of streptavidin, and subsequent immobilization of biotinylated antibodies, and (ii) Au surfaces showing almost no affinity for the same streptavidin and antibody solutions. The surface interactions were monitored by quartz crystal microbalance with dissipation monitoring (QCM-D), and chemical analyses were performed by polarization modulation-reflexion absorption infrared spectroscopy (PM-RAIRS) and X-ray photoelectron spectroscopy (XPS) to assess the validity of the initial orthogonal assembly of APTES and thiol-OEG. Eventually, microscopy imaging of the modified Au/SiO(2) patterned substrates validated the specific binding of streptavidin on the SiO(2)/APTES areas, as well as the subsequent binding of biotinylated anti-rIgG and further detection of fluorescent rIgG on the functionalized SiO(2) areas. These results demonstrate a successful protocol for the preparation of patterned biofunctional surfaces, based on microfabricated Au/SiO(2) templates and supported by careful surface analysis. The strong immobilization of the biomolecules resulting from the described protocol is advantageous in particular for micropatterned substrates for cell-surface interactions.


Selective infection of human CD4+ cells by simian immunodeficiency virus: productive infection associated with envelope glycoprotein-induced fusion.
Simian immunodeficiency virus (SIV) and human immunodeficiency virus share the property of tropism for CD4-bearing cells. Infection is initiated by a high-affinity interaction between CD4 and conserved domains on the viral envelope glycoprotein. In this report, we demonstrated that SIV had a restricted host range among human CD4+ cells when compared with human immunodeficiency virus type 1 or type 2. This restricted tropism was associated with the inability of the SIV envelope glycoprotein to induce membrane fusion in cells not susceptible to productive exogenous infection by SIV. We conclude that the major route of SIV entry into CD4+ cells is by envelope-mediated direct fusion with the cell and that additional envelope-cell interactions after CD4 binding are required for productive infection.


[Imaging superficial skin tumors of the ENT area. High frequency ultrasound in comparison with computerized tomography and magnetic resonance tomography].
In order to improve the preoperative diagnosis of superficial skin tumors in the head and neck, 32 patients with 42 basal cell carcinomas, squamous cell carcinomas and malignant melanomas were investigated using different imaging techniques. All patients were examined preoperatively with high-frequency ultrasound (HFU), computed tomography (CT) and magnetic resonance imaging (MRI). New high-frequency ultrasonic scanners (15- and 20-MHz) having an axial resolution of 50-90 microns permit visualization of dermal and cartilaginous structures with an anatomical accuracy to a range of 15 mm in tissue. Exact measurement of the skin tumors and their relation to adjacent structures was feasible. Histologically different tumors could be discriminated by their echo-structure in 80% of the cases. CT and MRI provided additional information when the tumor extension perpendicular to the skin exceeded 15 mm. If tumor extension was less than 15 mm, CT and MRI were inferior to high-frequency ultrasound in the diagnosis of superficial skin tumors and did not provide any additional information. The experience reported has shown that high-frequency ultrasound is a valuable tool for preoperative evaluation of superficial skin tumors in terms of tumor extension and possible invasion of functionally and esthetically important adjacent structures. This knowledge can support preoperative planning of possible resections as well as reconstruction and may help to obtain an appropriate informed consent.


Proteomic profiling of macrophages by 2D electrophoresis.
The goal of the two-dimensional (2D) electrophoresis protocol described here is to show how to analyse the phenotype of human cultured macrophages. The key role of macrophages has been shown in various pathological disorders such as inflammatory, immunological, and infectious diseases. In this protocol, we use primary cultures of human monocyte-derived macrophages that can be differentiated into the M1 (pro-inflammatory) or the M2 (anti-inflammatory) phenotype. This in vitro model is reliable for studying the biological activities of M1 and M2 macrophages and also for a proteomic approach. Proteomic techniques are useful for comparing the phenotype and behaviour of M1 and M2 macrophages during host pathogenicity. 2D gel electrophoresis is a powerful proteomic technique for mapping large numbers of proteins or polypeptides simultaneously. We describe the protocol of 2D electrophoresis using fluorescent dyes, named 2D Differential Gel Electrophoresis (DIGE). The M1 and M2 macrophages proteins are labelled with cyanine dyes before separation by isoelectric focusing, according to their isoelectric point in the first dimension, and their molecular mass, in the second dimension. Separated protein or polypeptidic spots are then used to detect differences in protein or polypeptide expression levels. The proteomic approaches described here allows the investigation of the macrophage protein changes associated with various disorders like host pathogenicity or microbial toxins.


First-line chemotherapy with vinorelbine, gemcitabine, and carboplatin in the treatment of brain metastases from non-small-cell lung cancer: a phase II study.
On the basis of the hypothesis that responsiveness of brain metastases (BM) to chemotherapy is primarily determined by the chemosensitivity of primary tumor, rather than the ability of cytotoxic agents to penetrate the blood-brain barrier, we addressed the role of a new combination regimen with Vinorelbine (VNR), Gemcitabine (GEM), and Carboplatin (CBDCA) as a primary treatment modality in non-small-cell lung cancer (NSCLC) patients with BM. Twenty-two consecutive chemotherapy-naïve patients with documented BM from NSCLC and at least 1 evaluable extracerebral lesion were enrolled in this phase II study. Vinorelbine (25 mg/m2) and GEM (1000 mg/m2) were given on day 1, combined with a fixed daily dose of CBDCA at AUC = 5.0 for three consecutive days. The cycle was repeated every three weeks in an outpatient setting. A total of 116 cycles was given (median 4, range 3-9 per patient). Specific evaluation of BM by contrast-enhanced computed tomography (CT) scan showed an overall response rate of 45% in 20 evaluable patients (95% confidence interval, 26-66%), with 3 (15%) complete and 6 (30%) partial remissions; in addition, three minor regressions, five disease stabilizations, and three progressions were found. Patients who responded for the brain also had a response at the extracerebral sites, and a benefit by a remission of symptoms and improvement of performance index was observed in 77% of the whole group. Median time to response was 10 weeks (range 6-12 weeks) and median response duration was 25 weeks (range 12-32 weeks). Median survival time was 33 weeks (range 18-62 + weeks) in the whole group and 48 weeks in responders (range 26-62 + weeks). The adopted schedule was well tolerated and easy to use in the outpatient setting, with good patient compliance. Our results, which are consistent with the study hypothesis, suggest that BM respond to chemotherapy in the same way as systemic disease and primary tumor, and further support the need for reconsideration of the role of chemotherapy in such a clinical setting. Controlled trials comparing chemotherapy with radiotherapy or concomitant sequential chemo-radiotherapy would be appropriate.


Expression of lncRNAs NEAT1 and lnc-DC in Serum From Patients With Behçet's Disease Can Be Used as Predictors of Disease.
Background: Behçet's disease (BD) is a chronic autoimmune disease. The early diagnosis of BD is very important to avoid serious and/or fatal complications such as eye damage, severe neurological involvement, and large vessel occlusion. New, sensitive biomarkers would aid in rapid diagnosis, the monitoring of disease activity, and the response to treatment. Methods: This study's aim is to identify two immune system-related BD biomarkers. We measured long non-coding RNAs (lncRNAs) NEAT1 (nuclear-enriched abundant transcript 1), and lnc-DC (lncRNA in dendritic cells) in serum by real-time polymerase chain reaction (RT-PCR) in 52 BD patients and 52 controls. We analyzed the association between NEAT1 and lnc-DC and the clinical parameters of BD. Receiver operating characteristic (ROC) curve analysis was performed to explore the diagnostic performance of the studied genes. Results: Compared to controls, the significant upregulation of NEAT1 {median [interquartile range (IQR)] = 1.68 (0.38-7.7), p < 0.0001} and downregulation of lnc-DC [median (IQR) = 0.2 (0.12-1.39), p = 0.03] were detected in the sera collected from BD patients. Higher serum expression levels of NEAT1 and lnc-DC were significantly associated with the following clinical presentations: cutaneous lesions, vascular manifestations, articular manifestations, neurological manifestations, and higher disease activity score. Also, high NEAT1 levels were significantly associated with a negative pathergy test, while higher lnc-DC was significantly associated with a positive family history. ROC curves showed that NEAT1 and lnc-DC levels in serum could be used as predictors of BD with high specificity and fair sensitivity. NEAT1 had an area under the curve (AUC) of 0.692 (95% CI: 0.591-0.794, p = 0.001), and lnc-DC had an AUC of 0.615 (95% CI: 0.508-0.723, p = 0.043). Conclusion: Serum lncRNAs NEAT1 and lnc-DC are biomarkers for BD.


Analysis of gunshot residues on human tissues and clothing by X-ray microfluorescence.
The analysis of gunshot residues on human tissues and clothing in suicide, homicide, suspicious death, or attempted murder events, permits the forensic scientist to confirm the possibility of an entry wound caused by a gunshot bullet from a pistol, revolver, rifle, etc. The residues to be detected are lead (Pb), antimony (Sb), barium (Ba) usually from the primer, copper (Cu) and zinc (Zn) usually from the metal jacket bullet and iron (Fe) possibly from the barrel of the gun used. The presence or absence of these elements and their relative concentrations can help in the interpretation of the event.


Palliative care case managers in primary care: a descriptive study of referrals in relation to treatment aims.
Three important elements of the World Health Organization (WHO) definition of palliative care are: 1) it includes patients who may have cure or life prolongation as treatment aims besides palliative care; 2) it is not exclusively for cancer patients; and 3) it includes attention to the medical, psychological, social, and spiritual needs of the patients and their families. Case managers (nurses with expertise in palliative care) may assist generalist primary care providers in delivery of good palliative care. This study investigates the referral of patients to case managers in primary care with regard to the three elements mentioned: diagnosis, treatment aims, and needs as reflected in reasons given for referral. In this cross-sectional survey in primary care among case managers and referrers to case management, case managers completed questionnaires for 687 patients; referrers completed 448 (65%). Most patients referred have a combination of treatment aims (69%). Life expectancy and functional status of patients are lower for those with a treatment aim of palliation. Almost all (96%) of those referred are cancer patients. A need for psychosocial support is frequently given as a reason for referral (66%) regardless of treatment aim. Referrals to case managers reflect two of three elements of the WHO definition. Mainly, patients are referred for support complementary to medical care, and relatively early in their disease trajectory. However, most of those referred are cancer patients. Thus, to fully reflect the definition, broadening the scope to reach other patient groups is important.


Biocompatibility evaluation of surface-treated AISI 316L austenitic stainless steel in human cell cultures.
The effects of AISI 316L austenitic stainless steel, tested in untreated state or subjected to glow-discharge nitriding (at 10 or 20 hPa) and nitriding + post-oxidizing treatments, on human umbilical vein endothelial cells (HUVEC) and on peripheral blood mononuclear cells (PBMC) were evaluated. All the treated samples showed a better corrosion resistance in PBS and higher surface hardness in comparison with the untreated alloy. In HUVEC put in contact for 72 h with the sample types, proliferation and apoptosis decreased and increased, respectively, in the presence of the nitrided + post-oxidized samples, while only slight differences in cytokine (TNF-alpha, IL-6, and TGF-beta1) release were registered. Intercellular adhesion molecule-1 (ICAM-1) increased in HUVEC incubated with all the treated samples, while vascular cell adhesion molecule-1 (VCAM-1) and E-selectin increased in the presence of all the sample types. PBMC incubated for 48 h with the samples showed a decrease in proliferation and an increase in apoptosis in the presence of the untreated samples and the nitrided + post-oxidized ones. All the sample types induced a remarkable increase in TNF-alpha and IL-6 release in PBMC culture medium, while only the untreated sample and the nitrided at 10 hPa induced an increase in ICAM-1 expression. In HUVEC cocultured with PBMC, previously put in contact with the treated AISI 316L samples, increased levels of ICAM-1 were detected. In HUVEC coincubated with the culture medium of PBMC, previously put in contact with the samples under study, a noteworthy increase in ICAM-1, VCAM-1, and E-selectin levels was always registered, with the exception of VCAM-1, which was not affected by the untreated sample. In conclusion, even if the treated samples do not show a marked increase in biocompatibility in comparison with the untreated alloy, their higher corrosion resistance may suggest a better performance as the contact with physiological environment becomes longer.


Normal and leukemic hemopoiesis compared.
Using colony assays for human erythropoietic (BFU-E, CFU-E) and granulopoietic (CFU-C) progenitors, normal and leukemic myelopoietic differentiation were compared; similar patterns were found in both. However, the origin of blast cells characteristic of the disease could not be established indicating the need for a direct approach to these cells. A colony assay for blast cells in acute myeloblastic leukemia is described. Blast cell colony-formation is significantly correlated with blast cell number, and the colonies contain cells of blast like morphology without differentiation markers. It is proposed that this method, taken in conjunction with results from assays of myelopoiesis and lymphopoiesis, may provide a more complete picture of leukemic differentiation. It is anticipated that such a model will be useful in devising new therapies.


HI1 and I1 Resistance Plasmids from Salmonella enterica Serovar Typhimurium Strain SRC27 Are Epidemic.
Conjugative plasmids are a major contributor to the global spread of antibiotic resistance determinants, but the tracking of their evolutionary history is often neglected. Salmonella enterica serovar Typhimurium (S. Typhimurium) strain SRC27 was isolated from an equine infection in Australia in 1999. SRC27 was known to carry conjugative HI1 and I1 resistance plasmids. In this study, SRC27 was sequenced to determine the relationship between these HI1 and I1 resistance plasmids it was known to carry and HI1 and I1 resistance plasmids circulating worldwide. The resistance genes in the HI1 plasmid, pSRC27-H, are all located in a single complex 34.7 kb resistance region. The backbone sequence and location of the pSRC27-H resistance island were used to identify the most closely related HI1 plasmids among the >90 that have been sequenced since 2011. This defined a sublineage of 20 type 2 HI1 plasmids that have been circulating in Europe, Asia, North America, and Australia since at least 1993. The overall resistance gene content of these HI1 plasmids differs, indicating extensive evolution in situ through the acquisition of additional transposons and deletion or replacement of ancestral regions. The I1 plasmid contains a complete copy of Tn5393a, containing the strAB genes that confer resistance to streptomycin. The precise location of Tn5393a in the backbone also defined a globally disseminated sublineage of I1 plasmids, many of which have also acquired additional resistance determinants. The sequence revealed that SRC27 also carried two additional plasmids, the pSLT-type FIB(S):FII(S) virulence plasmid and a small cryptic theta-replicating Col156 plasmid.


Prevalence of functional gastrointestinal disorders in infants and young children in China.
The prevalence of functional gastrointestinal disorders (FGIDs) in children, particularly from Asia, is largely unknown. There are not many studies done in Asia especially using the Rome IV criteria. The aim of this study is to assess the prevalence of FGIDs in infants and young children in a representative sample in China. A prospective, cross-sectional, community-based survey was conducted among healthy infants and young children between the ages of 0-4 years in Jinhua and Shanghai, China. A total of 2604 subjects (1300 subjects from Jinhua and 1304 subjects from Shanghai) completed a validated questionnaire on pediatric gastrointestinal symptoms. FGIDs in infants and young children were diagnosed using the Rome IV criteria. According to the Rome IV criteria, the prevalence of having a FGID in Chinese infants and young children is 27.3%. Infant regurgitation (33.9%) was the most common FGID among the 0-6 months old while functional constipation (7.0%) was the most common among the 1-4 years old. Risk factor analysis revealed that prevalence of infantile colic was higher with better maternal education and low birth weight. Prevalence of infantile regurgitation was significantly greater in males, living in a rural area, being exclusively breast fed at least up to 4 months and starting formula feeds within the first month. The risk of functional constipation was lower for infants who were delivered vaginally. Infantile regurgitation was the most common FGID in Chinese infants while functional constipation was most prevalent among young Chinese children. Netherlands Trial Registry Identifier: NL6973/NTR7161 .


Ergosterol biosynthesis in Aspergillus fumigatus: its relevance as an antifungal target and role in antifungal drug resistance.
Ergosterol, the major sterol of fungal membranes, is essential for developmental growth and the main target of antifungals that are currently used to treat fatal fungal infections. Emergence of resistance to existing antifungals is a current problem and several secondary resistance mechanisms have been described in Aspergillus fumigatus clinical isolates. A full understanding of ergosterol biosynthetic control therefore appears to be essential for improvement of antifungal efficacy and to prevent antifungal resistance. An ergosterol biosynthesis pathway in A. fumigatus has been proposed with 14 sterol intermediates resulting in ergosterol and another secondary final compound C-24 ethyl sterol. Transcriptomic analysis of the A. fumigatus response to host-imposed stresses or antifungal agents is expanding our understanding of both sterol biosynthesis and the modes of action of antifungal drugs. Ultimately, the identification of new targets for novel drug design, or the study of combinatorial effects of targeting sterol biosynthesis together with other metabolic pathways, is warranted.


Cutaneous Spitzoid melanoma in a very young girl of Asian descent.
Cutaneous melanoma is extremely uncommon in children. Further, Asian-Americans appear to be at decreased risk for cutaneous melanoma. The authors present the case of a prepubescent Asian girl who presents with the rare spitzoid variant of cutaneous melanoma. The patient is a 4-year-old girl of Chinese descent who presented with a red, raised nodule, which increased in size over a 3-month period. She underwent wide local excision with sentinel lymph node dissection. On histopathologic analysis, she was found to have Spitzoid melanoma of childhood/adolescence. Spitzoid melanoma in children is rare and incompletely understood. A recent systematic review was only able to identify 82 such cases published over a 57-year period. To our knowledge, this is the first report of Spitzoid melanoma in a paediatric age patient of Asian descent. While this clearly is an uncommon demographic, it seeks to highlight important differences in racial predilection for Spitzoid melanoma.


X-ray absorption fine structure study of multinuclear copper(I) thiourea mixed ligand complexes.
X-ray absorption fine structure spectra of five copper(I) thiourea complexes [Cu4(thu)6 (NO3)4 (H2O)4] (1), [Cu4(thu)9 (NO3)4 (H2O)4] (2), [Cu2(thu)6 (SO4) H2O] (3), [Cu2(thu)5 (SO4) (H2O)3] (4), and [Cu(thu)Cl 0.5H2O] (5) have been investigated. Complexes 1 and 3 are supposed to have one type of copper centers in trigonal planar and tetrahedral environment, respectively. Complexes 2 and 4 are supposed to have two types of copper centers, one center having trigonal planar geometry and another center having tetrahedral geometry. The aim of the present work is to show how extended X-ray absorption fine structure (EXAFS) spectra of these complexes, having different types of coordination environment, can be analyzed to yield the coordination geometry around one type of copper centers present in complexes 1 and 3, and two types of copper centers present in complexes 2 and 4. The crystal structure of complex 5 is unavailable due to inability of growing its single crystals, and hence the coordination geometry of this complex has been determined from EXAFS. The structural parameters determined from the EXAFS spectra have been reported and the coordination geometry has been depicted for the metal centers present in all the five complexes. Also, the chemical shifts have been used to determine the oxidation state of copper in these complexes. The X-ray absorption near edge spectra features have also been correlated with the coordination geometry. Also, the presence of both three and four coordinated Cu(I) centers in complexes 2 and 4 has been suggested from a comparison of the intensity of the feature at 8984 eV with those of 1 and 3. Further, in case of complex 5, the high intensity of peak A at 8986.5 eV is found to correspond to the presence of Cl coordinated to the copper center.


Microwell enumeration of viable Saprolegniaceae in water samples.
Existing methods for enumeration of viable Saprolegniaceae propagules in water are laborious, time consuming and prevent examination of large numbers of samples or samples with high spore loads. In the present study a microwell plate (MWP) assay for estimation of Saprolegniaceae in water samples, modified from Hagen (1992), was evaluated. The ability of the assay to recover Saprolegniaceae was assessed by applying it to spore suspensions with four predetermined concentrations, 500-10,000 spores per liter of samples tested. The method also was used to analyze a set of field samples and compare it to a standard filtration method to ascertain its practicability. The MWP assay underestimated the number of spores in the test suspensions with predetermined concentrations. The accuracy of the assay varied with spore concentration, giving the lowest recovery (62.5%) at low spore numbers and the highest (86%) at intermediate concentrations (1000-5000 spores/L) for both isolates and growth media. The findings indicate that spores aggregate with increasing concentration. When applied to field samples the assay clearly distinguished among samples with presumptive differences in spore load and yielded significantly higher counts than the filtration method. The results justify the MWP method foruse in estimation of Saprolegniaceae in water bodies particularly relevant for monitoring of spore load in aquaculture as well as in ecological studies.


Toluene diisocyanate respiratory reactions. I. Reassessment of the problem.
A series of workers with exposure to and respiratory symptoms from toluene diisocyanate (TDI) was compared with a group of exposed, asymptomatic workers and with normal controls using immunologic and clinical evaluations. Improved understanding of TDI-induced respiratory disease may best be achieved by categorizing the symptomatic workers into at least 3 and possibly 4 groups: immunologic TDI asthma; pre-existing chronic respiratory disease exacerbated or unaffected by TDI; asthma coincidental with TDI exposure, and possibly TDI respiratory disease secondary to toxic or inflammatory mechanisms.


Epitaxial growth and lithium ion conductivity of lithium-oxide garnet for an all solid-state battery electrolyte.
Epitaxial thin films of Al-doped Li7La3Zr2O12 (LLZO) with a cubic garnet-type structure were successfully synthesized using pulsed laser deposition to investigate the lithium ion conduction in grains. Two orientations of the films were obtained depending on the Gd3Ga5O12 (GGG) substrate orientation, LLZO(001)/GGG(001) and LLZO(111)/GGG(111). The ionic conductivities in the grains of the (001) and (111) films were 2.5 × 10(-6) and 1.0 × 10(-5) S cm(-1) at 298 K, respectively, which were lower than those of polycrystalline LLZO of over 10(-4) S cm(-1). X-ray reflectometry and inductively coupled plasma mass spectrometry revealed a large amount of Al(3+) of over 0.6 moles substituted for Li(+). These results indicate that the Al(3+) substitution in the LLZO lattice decreases the number of movable lithium ions and blocks the three-dimensional lithium migration pathway. The lattice mismatch between the film and the substrate induced the lattice distortion of the LLZO, resulting in different conductivities between the (001) and (111) films. The epitaxial-film model system directly clarified a substantial impact of the Al substitution and the lattice distortion on the lithium ion conductivity in the LLZO.