Effectiveness of music therapy and progressive muscle relaxation in reducing stress before exams and improving academic performance in Nursing students: A randomized trial.
Nursing students experiencing high stress levels before exams could suffer worse academic performance. We evaluated an intervention combining Progressive Muscle Relaxation (PMR) and music therapy on the decrease of before exams stress and the improvement of academic results. Randomized controlled trial including students from the Nursing Degree during the first semester of the 2017-2018 academic year. All participants were randomized to the control (CG) or the experimental group (EG). The CG took the exam as usual whereas in the EG, PMR and music therapy were performed before exams. Blood samples were drawn to investigate variations in biochemical parameters. The academic performance was assessed by the score obtained in the "Clinical Nursing" exam. We included 112 students (75% females, mean age 24.3 ± 6.2 years, 56 students in every group). There were no differences in any parameter during the first measurement. Regarding the second measurement, we observed a reduction in heart rate for the EG and an increase in blood pressure, heart rate, and cortisol for the CG. Indeed, these parameters were significantly higher compared to the EG. The EG had a mean score of 5.07 ± 1.59 in the Clinical Nursing exam, which was significantly higher compared to the CG (4.42 ± 1.58, p = 0.033). The proportion of fails in the CG was also higher (62.5% vs. 42.9%, p = 0.037). In this study including students from the Nursing degree, the combination of PMR and music therapy was effective for the control and decrease of stress before exams, and also demonstrated improvements in academic results.


9-Thiourea Cinchona alkaloid supported on mesoporous silica as a highly enantioselective, recyclable heterogeneous asymmetric catalyst.
A readily recycled and regenerated heterogeneous catalyst of 9-thiourea epi-quinine supported on mesoporous silica exhibits enhanced enantioselectivity (up to 99.2%) in the asymmetric Friedel-Crafts reaction of imines with indoles.


Promoting research partnerships to reduce health disparities among vulnerable populations: sharing expertise between majority institutions and historically black universities.
This chapter focuses on promoting cultural competence in research and the care of vulnerable populations by establishing inter-university nursing partnership centers for health disparities research between historically Black universities and minority-serving institutions and research-intensive majority institutions. The Hampton-Penn Center to Reduce Health Disparities (HPC), an inter-university collaborative center funded through the National Institutes of Health (NIH) National Institute of Nursing Research (NINR) P20 funding mechanism, is discussed as the exemplar. The mission of the Hampton-Penn Center is to promote culturally competent research on health promotion and disease prevention and the examination of how culture, race and ethnicity and their interactions with the health care system and the larger society influence health outcomes and the occurrence of health disparities. The history, goals, and conceptual model underlying this collaborative effort between the University of Pennsylvania and Hampton University Schools of Nursing are described as are the accomplishments and lessons learned to date. Based upon the Hampton-Penn experience, recommendations for similar collaborations to reduce health disparities among vulnerable populations are made in three major areas: (a) increasing the study of the multi-system level factors that contribute to health disparities among vulnerable populations, (b) promoting the development of culturally competent research on health disparities, and (c) promoting the recruitment and training of health researchers who are themselves members of vulnerable populations.


Export of health services from developing countries: the case of Tunisia.
Although the subject of health services exports by developing countries has been much discussed, the phenomenon is still in its early stage, and its real implications are not yet clear. Given the rapid development in this area, little empirical data are available. This paper aims to fill this gap by providing reliable data on consumption of health services abroad (GATS mode 2 of international service supply). It starts by assessing the magnitude of the volume of international trade in health services. This is followed by an in-depth analysis of the case of Tunisia based on an original field research. Because of the high quality of its health sector and its proximity with Europe, Tunisia has the highest export potential for health services in the Middle-East and North Africa (MENA) Region. Health services exports may represent a quarter of Tunisia's private health sector output and generate jobs for 5000 employees. If one takes into account tourism expenses by the incoming patient (and their relatives), these exports contribute to nearly 1% of the country's total exports. Finally, this case study highlights the regional dimension of external demand for health services and the predominance of South-South trade.


Stimulation by a TRH precursor, TRH-Gly, of TSH and PRL secretion in rats: effect of starvation.
The hypophysial activities of a possible direct precursor of thyrotropin (TSH)-releasing hormone (TRH), TRH-Gly, were evaluated in estrogen, progesterone-primed rats under urethane anesthesia. Intravenous administration of TRH-Gly in doses of 2-200 micrograms caused a significant and dose-dependent increase in blood TSH and prolactin (PRL). The stimulatory activity of TRH-Gly was 170 to 400-times less potent than that of TRH. The lower potency was confirmed by the action of TRH-Gly on the anterior pituitary cells in vitro. In starved rats, TRH-Gly apparently stimulated TSH and PRL secretion in a dose-dependent manner, and the stimulatory activity increased in starved rats as compared to normal controls. TRH-Gly did not affect [3H-MeHis]TRH binding in pituitary plasma membranes. These data imply that large amounts of TRH-Gly may have significant biological activities and these are potentiated in the starved condition.


First description of the male of Solenura ania (Walker) (Hymenoptera: Pteromalidae), a giant pteromalid parasitoid of Trichoferus campestris (Faldermann), with special reference to its sexual dimorphism.
The giant pteromalid wasp Solenura ania (Walker) has a distinct sexual dimorphism. The metallic blue female is about 28 mm long and the metallic green male is only about 6 mm in length. This species is an ectoparasitoid of some woodborers, such as Trichoferus campestris (Faldermann), a pest of many live trees and wood furniture and a quarantine pest in many countries. However, the male of this pteromalid was not described prior to this study. The male of the species is first described, based on newly-collected material. Photographs of habitus, head, mesosoma, metasoma and other structures of both sexes are provided to facilitate recognition of this giant pteromalid. Sexual dimorphism is also compared in the present study.


GNAQQ209L expression initiated in multipotent neural crest cells drives aggressive melanoma of the central nervous system.
Primary leptomeningeal melanocytic neoplasms represent a spectrum of rare tumors originating from melanocytes of the leptomeninges, which are the inner two membranes that protect the central nervous system. Like other non-epithelial melanocytic lesions, they bear frequent oncogenic mutations in the heterotrimeric G protein alpha subunits, GNAQ or GNA11. In this study, we used Plp1-creERT to force the expression of oncogenic GNAQQ209L in the multipotent neural crest cells of the ventro-medial developmental pathway, beginning prior to melanocyte cell differentiation. We found that this produces leptomeningeal melanocytic neoplasms, including cranial melanocytomas, spinal melanocytomas, and spinal melanomas, in addition to blue nevus-like lesions in the dermis. GNAQQ209L drove different phenotypes depending upon when during embryogenesis (E9.5, E10.5, or E11.5) it was induced by tamoxifen and which Cre driver (Plp1-creERT, Tyr-creERT2 , or Mitf-cre) was used. Given these differences, we propose that melanocytes go through temporary phases where they become sensitive to the oncogenic effects of GNAQQ209L . R26-fs-GNAQQ209L ; Plp1-creERT mice will be useful for defining biomarkers for potentially aggressive leptomeningeal melanocytomas and for developing new therapeutics for advanced disease.


The formation of radiolabeled N1- and N8-acetylspermidine in various rat organs following [14C]spermidine administration.
To detect the in vivo formation of acetylspermidine, three female Sprague-Dawley rats were injected intravenously with 20 muCi of [14C]spermidine. Twenty-four hours after the injection of the radiolabel, the kidneys, liver, lungs, pancreas, small intestine, spleen, stomach and thymus were removed under Halothane anesthesia. High performance liquid chromatography (HPLC) of the pooled radiolabeled extracts from each tissue demonstrated the presence of a 14C-labeled material which co-chromatographed with an acetylspermidine standard. Thin layer chromatography (TLC) of the HPLC eluent demonstrated the presence of both radiolabeled N1- and N8-acetylspermidine in the tissues. Concentrations of labeled acetylspermidine ranged from 0.27 to 1.9% of the total tissue radiolabel. The N1-to N8-acetylspermidine ratio in tissues ranged from approx. 5 to 1 in the thymus to 1.5 to 1 in the liver.


Cervical carcinoma in the setting of uterovaginal prolapse: comparing standard versus tailored management.
Cervical cancer in the setting of uterovaginal prolapse is exceedingly rare. Altered anatomy can complicate treatment of underlying cancer. We first present a rare case of cervical cancer with invasion of uterovaginal prolapse as well as a systematic review of similar reported cases in the literature. The objective of this study was to compare the practice patterns and outcomes regarding cervical cancer with invasion of procidentia. We conducted a systematic search of online databases (PubMed, Embase, Medline and the Cochrane Library) from 1990 to 2018 of all the cases of cervical cancer associated with stage III-IV uterovaginal prolapse. Patient demographics, pathology, surgical management, chemotherapy, radiation and disease-free survival were compared. Fifteen reported cases of cervical cancer in the setting of procidentia were identified (squamous cell carcinoma-14, clear cell carcinoma-1). The mean age at diagnosis was 74 years (range 54-89). Thirteen percent (n = 2) of cases presented with FIGO stage I disease, 67% (n = 10) with stage II, and 20% (n = 3) with stage III. All cases had stage III-IV uterovaginal prolapse. 73% (11) were treated surgically including nine patients who underwent vaginal hysterectomy. Among patients who underwent primary surgery, 7% (1) received adjuvant chemotherapy, 33% (5) adjuvant radiotherapy and 21% (3) both adjuvant chemotherapy and radiation. 33% (5) of surgical cases included procedures to address the pelvic organ prolapse (colpoclesis (n = 3), uterosacral suspension (n = 1) and anterior posterior repair (n = 1)). Two patients died from the disease within 12 months, one patient died from other causes within 1 month, and the remainder of patients were free of disease at last reported follow-up (Table 1). Cervical cancer in the setting of stage III-IV uterovaginal prolapse can be managed successfully with standard treatment strategies (primary surgery with adjuvant therapy as necessary versus chemoradiation). When patients are surgical candidates, techniques to address the underlying prolapse can be used for symptomatic improvement.


Transition of mesenchymal stem/stromal cells to endothelial cells.
Mesenchymal stem/stromal cells (MSCs) are heterogeneous. A fraction of these cells constitute multipotent cells that can self-renew and mainly give rise to mesodermal lineage cells such as adipocytes, osteocytes and chondrocytes. The ability of MSCs to differentiate into endothelial cells remains controversial. Isolation and in vitro manipulation of MSCs before clinical application are important steps. High numbers of MSCs are needed, requiring the in vitro expansion of these clinically important cells. To this end, a well-controlled procedure for MSC isolation and maintenance in culture is necessary.


Degradation of the precursor of mitochondrial aspartate aminotransferase in chicken embryo fibroblasts.
The precursor of mitochondrial aspartate aminotransferase accumulates in the cytosol of cultured chicken embryo fibroblasts if its import into mitochondria is inhibited by an uncoupling agent. However, its accumulation is limited by degradation with a half-life of only approximately 5 min (Jaussi, R., Sonderegger, P., Flückiger, J., and Christen, P. (1982) J. Biol. Chem. 257, 13334-13340). The aim of the present study was the characterization of the proteolytic system(s) responsible for this very rapid intracellular degradation. On depleting chicken embryo fibroblasts of ATP, the rate of degradation of the precursor was lowered by approximately 70%. Chicken embryo fibroblasts depleted of divalent metal ions showed a degradative activity of 10% of the initial value. Reconstitution of these cells with Mg2+ and Ca2+ increased the degradative activity from 10 to 107 and 24%, respectively. Thiol reagents almost completely prevented the degradation, whereas specific peptide inhibitors of cysteine proteases or inhibitors of intralysosomal proteolysis decreased the rate of degradation by only approximately 30%. Inhibitors of serine proteases had little effect. No rapid degradation of the precursor was observed in crude extracts of chicken embryo fibroblasts. The data indicate that the bulk of the precursor accumulated under conditions of import block is degraded by one or several cytosolic proteases dependent on ATP, Mg2+, and thiol groups of unknown localization, conceivably by proteolytic enzymes identical with or similar to one of the high molecular weight cytosolic proteases (Waxman, L., Fagan, J.M., Tanaka, K., and Goldberg, A. L. (1985) J. Biol. Chem. 260, 11994-12000). The rest of the precursor appears to be degraded by lysosomes.


Influence of Plasmodium gametocyte carriage on the prevalence of fever, splenomegaly and cardiovascular parameters in children less than 15 years in the Mount Cameroon area: cross sectional study.
Cardiovascular parameters can be impaired by repeated infections with P. falciparum. This study aimed at investigating the influence of gametocyte carriage on; the prevalence of fever and splenomegaly, blood pressure, heart rate and haematological indices in children <15 years, in the Mount Cameroon area. A cross-sectional study was carried out, from February to July 2013. A child with axillary body temperature ≥37.5 °C was considered febrile and splenomegaly was investigated by palpation. Systolic and diastolic blood pressures as well as heart rate were assessed by non-invasive methods. Malaria parasites were detected and density assessed from Giemsa-stained thin and thick blood films. An auto haematology analyser was used to obtain complete blood count values such as haemoglobin (Hb), haematocrit (Hct), red blood cell (RBC) and white blood cell (WBC) counts, mean corpuscular volume (MCV), mean corpuscular haemoglobin concentration (MCHC), and mean corpuscular haemoglobin (MCH). Univariate analyses were used to examine influence of gametocyte carriage on fever and splenomegaly while, multiple linear regression models were used to evaluate influence of independent variables on the dependent variables. Of a total of 454 children examined, malaria parasitaemia, fever, splenomegaly and gametocyte carriage were detected in 36.6, 21.6, 14.3 and 7.3 % of them respectively. Children who were asexual parasite and gametocyte positive (ASP + Gam Pos) had significantly highest (P = 0.03, P = 0.002) prevalence of fever and splenomegaly (39.4 %, 33.3 %) respectively than their aparasitaemic (AP) and asexual parasite positive (ASP Pos) equivalents (19.0 %, 10.9 % and 22.8 %, 16.9 % respectively). The presence of asexual malaria parasitaemia significantly influenced the MCV (P = 0.03), MCH (P = 0.03) and heart beats /min (0.03) while gametocytaemia significantly influenced the Hb (P < 0.001), Hct (P < 0.001), RBC (P < 0.001) and systolic blood pressure (P < 0.05). Gametocyte carriage significantly influenced the prevalence of fever, splenomegaly and some cardiovascular indices. In effect, children concurrently having asexual parasitaemia and gametocytes had significantly lower, Hct, Hb levels, RBC and platelet counts and systolic blood pressure.


Rapid Intubation Sequence: 4-Year Experience in an Emergency Department.
The rapid intubation sequence is advanced airway management that effectively ensures an adequate supply of oxygen in critically ill patients. The medical personnel in the emergency department performed this procedure. To describe the main characteristics of the rapid intubation sequence in an emergency department of a high complexity hospital. This is a descriptive, cross-sectional, retrospective study. We included all older patients with a rapid intubation sequence requirement in the emergency department from 2014 to 2017. We used central tendency measures for numerical variables and proportions for categorical variables. A total of 401 patients were eligible for this analysis. The main indication for intubation was the Glasgow Coma Scale = <8 in 170 patients (42.4%), followed by hypoxemia in 142 patients (35.4%). In 36 patients, at least one complication occurred. RSI was performed in 54.4% by emergency physician. RSI was successful on the first attempt in 90.5%. Only 36 patients (9%) presented complications. In this study, we found that the rapid intubation sequence was not related to a high proportion of complications. Perhaps, this is attributed to the degree of medical training and the use of emergency department protocols in our hospital.


Single molecule and single atom sensors for atomic resolution imaging of chemically complex surfaces.
Individual Xe atoms as well as single CO and CH(4) molecules adsorbed at the tip apex of a scanning tunneling microscope (STM) function as microscopic force sensors that change the tunneling current in response to the forces acting from the surface. An STM equipped with any of these sensors is able to image the short-range Pauli repulsion and thus resolve the inner structure of large organic adsorbate molecules. Differences in the performance of the three studied sensors suggest that the sensor functionality can be tailored by tuning the interaction between the sensor particle and the STM tip.


T wave morphology changes during hemodialysis.
Risk stratification for sudden cardiac death in hemodialysis (HD) patients is an unmet clinical need. Non invasive electrophysiological testing is challenging in these patients due to their oscillating cardiovascular and electrolyte status induced by the intermittent HD treatment. We hypothesized that continuous electrocardiographic monitoring during their regular HD session can provide reproducible repolarisation profiles. Continuous 12-lead digital electrocardiographs (ECGs) were recorded during dialysis in stable patients and were repeated at two-week intervals for 5 times. QRS-to-T angle (TCRT), principal component analysis (PCA) ratio and T wave morphology dispersion (TMD) were calculated every 5s in overlapping 10-s ECG segments. Serum electrolytes and plasma parathyroid hormone (PTH) levels were measured prior to the first recording. There were 319 acceptable recordings from 76 hemodialysed patients. Repeated Measures Anova showed intra-subject reproducibility of all descriptors. Mean PCA ratio and TMD values increased through dialysis and their intradialytic change correlated with heart rate changes (r = 0.305, p = 0.007 and r = 0.287, p = 0.012, respectively). TCRT showed a variable response to HD and the intradialytic change correlated positively with PTH levels (r = 0.284, p = 0.023). Repolarisation descriptors demonstrate subject-specific dynamic profiles during HD. PTH has a role in dynamics of myocardial repolarisation. The potential clinical utility of continuous intradialytic ECGs for risk stratification purposes should be prospectively evaluated.


Death due to unsuspected acute myeloid leukaemia: an unusual forensic diagnosis.
Acute myeloid leukaemia (AML) is a rare haematologic cancer with a rapid increase in blast cells, which need to be rapidly diagnosed and treated. The aim of this report is to analyse the rare phenomenon of AML diagnosed at autopsy after sudden death. We report three cases of AML and perform a literature review using the mesh terms "sudden death" and "leukaemia". We report the cases of three young women diagnosed with AML only after autopsy. We found seven articles which reported sudden death due to AML diagnosed at autopsy. Diagnosis of AML during autopsy is rare but can raise forensic issues. A complete autopsy with pathology analysis is needed.


HSP70-controlled GFP expression in transiently transformed schistosomes.
Among the parasitic helminths schistosomes are of high medical and economic importance. Despite of the world-wide relevance of this parasite, very little is known about the cellular mechanisms controlling its development and concerning the host-parasite interaction. Within the last decade a great effort has been made in this blood fluke to identify genes which play important roles during these processes. However, molecular analysis was limited by the fact, that neither function nor regulation of candidate genes could be investigated in this organism due to the lack of transformation protocols. Here, we present the strategy of ballistic gene transfer to introduce and characterize transgenes in different schistosome life stages. As a transformation vector, the heat shock protein 70 (hsp70) gene promoter and terminator from Schistosoma mansoni were cloned and fused to the green fluorescent protein (GFP) reporter gene. In a first attempt, the hsp70--GFP vector was successfully tested in a eukaryotic cell line. Thereafter, adult male schistosomes and sporocysts were transformed with this vector, and GFP expression was demonstrated using molecular and microscopical methods. PCR, reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blot analyses confirmed the presence, transcription and translation of the transgene in adults. Confocal laser scanning microscopy revealed GFP-activity at various sites along the surface of the worms after hs induction and within sporocysts. These results suggest diverse roles for hsp70 during the development of schistosomes. Furthermore, the results demonstrate the feasibility of this method and open the perspective to analyze a variety of molecular functions in schistosomes.


Resistance index, blood flow velocity, and resistance-area product in the cerebral arteries of very low birth weight infants during the first week of life.
Cerebral artery Doppler ultrasound recordings, and intra-arterial pressure measurements have been made from 27 very low birth weight infants during the first week of life. These data were used to calculate Pourcelot's resistance index (RI), mean blood flow velocity, and resistance-area product (RAP), in both the anterior and middle cerebral arteries. There was a good degree of correlation between recordings from different sites on the same occasion, but absolute values were site dependent. Over the first three days of life there was a significant increase in blood flow velocity in each of the vessels, and a significant fall in RI and RAP.


An exon map of the AZFc male infertility region of the human Y chromosome.
STS markers spanning the AZFc region of human Y Chromosome (Chr) were used to isolate a series of 14 P1 artificial chromosome (PAC) clones covering at least 560 kb of DNA. End clone analysis of these PAC clones was used to derive 10 new STS markers. Together with other markers mapped to the region, an STS content analysis was used to assemble these PAC clones into three distinct contigs. A minimum tiling path of ten PAC clones was subjected to exon trapping to identify potentially new genes mapping to the AZFs region. In all, 39 potential exons were isolated, including 2 exons from the DAZ gene, 3 exons from the BPY2 gene, 2 exons from the PRY gene, and 1 exon from a member of the RBM II gene family; all these genes have been shown previously to map to the AZFc region. One further exon was found that shows homology to the DFFRY gene, which maps to Yq11. 2, indicating that there may be a further copy of this gene or a pseudogene in the distal Yq euchromatin. The majority of the remaining potential exons appear to be novel, suggesting that additional genes lie in the AZFc region. Mapping of these exons by PCR analysis of somatic cell hybrids has shown that six of these exons are homologous to autosomal sequences, and five to sequences on the X Chr. RT-PCR analysis of primary cDNA from adult testis, brain, liver, and skeletal muscle mRNA has shown that 11 of the novel exons are expressed in one or a combination of these tissues, indicating that they form parts of genuine transcripts.


Defects in early cell recruitment contribute to the increased susceptibility to respiratory Klebsiella pneumoniae infection in diabetic mice.
Diabetes is associated with increased susceptibility to Klebsiella pneumoniae and poor prognosis with infection. We demonstrate accelerated mortality in mice with streptozotocin-induced diabetes following tracheal instillation of K. pneumoniae. Diabetic mice recruited fewer granulocytes to the alveolar airspace and had reduced early production of CXCL1, CXCL2, IL-1β and TNF-α following tracheal instillation of K. pneumoniae-lipopolysaccharide. Additionally, TLR2 and TIRAP expression following K. pneumoniae-lipopolysaccharide exposure was decreased in hyperglycemic mice. These findings indicate that impaired innate sensing and failure to rapidly recruit granulocytes to the site of infection is a mechanism for diabetic susceptibility to respiratory K. pneumoniae infection.


Cloning the argF gene from Escherichia coli K-12 with simian virus 40.
We have inserted a gene coding for ornithine transcarbamylase (OTCase) from Escherichia coli K-12 into the late gene region of simian virus 40 (SV40) DNA and propagated the hybrid molecules as free episomes or by co-infection with an SV40 tsA helper virus. In the first case, the E. coli argF gene was inserted via the EcoRI and BamHI termini in the late gene region of SV40 and the recombinant molecules were used to transfect monkey kidney cells. The hybrid DNA, which was too large to be encapsidated, was replicated for a short time (14 days) but was eventually lost from the surviving cells. In order to allow the argF gene to be packaged into virions, we purified two SV40 vectors containing large deletions of late gene region sequences. One was a 3325 base pair segment from a HaeII + BamHI digest. The argF gene was joined to both vectors at the BamHI site and these linear molecules were used to transfect monkey cells in the presence of SV40 tsA58 DNA as helper. These hybrid DNAs were replicated and packaged into virions. Late in the lytic infection of monkey cells, polyadenylated, cytoplasmic argF transcripts were detected, but significant translation of these trancripts was not observed.


Purification and characterization of extracellular PHB depolymerase enzyme from Aeromonas caviae Kuk1-(34) and their biodegradation studies with polymer films.
PHB depolymerase enzymes are able to breakdown the PHB polymers and thereby get significant economic value in the bioplastics industry and for bioremediation as well. This study shows the purification of novel extracellular PHB depolymerase enzyme from Aeromonas caviae Kuk1-(34) using dialysis followed by gel filtration and HPLC. The purification fold and yield after HPLC were 45.92 and 27.04%, respectively. HPLC data showed a single peak with a retention time of 1.937 min. GC-MS analysis reveals the presence of three compounds, of which 1-Dodecanol was found to be most significant with 54.48% area and 8.623-min retention time (RT). The molecular weight of the purified enzyme was obtained as 35 kDa with Km and apparent Vmax values of 0.769 mg/mL and 1.89 U/mL, respectively. The enzyme was moderately active at an optimum temperature of 35 °C and at pH 8.0. The stability was detected at pH 7.0-9.0 and 35-45 °C. Complete activity loss was observed with EDTA, SDS, Tween-20 at 5 mM and with 0.1% Triton X 100. A biodegradation study of commercially available biodegradable polymer films was carried out in a liquid medium and in soil separately with pure microbial culture and with purified enzyme for 7, 14, 28, and 49 consecutive days. In a liquid medium, with a pure strain of Aeromonas caviae Kuk1-(34), the maximum degradation (89%) was achieved on the PHB film, while no changes were observed with other polymer films. With purified enzyme in the soil, 71% degradation of the PHB film was noticed, and it was only 18% in the liquid medium. All such weight analysis were confirmed by SEM images where several holes, pits, grooves, crest, and surface roughness are clearly observed. Our results demonstrated the potential utility of Aeromonas caviae Kuk1-(34) as a source of extracellular PHB depolymerase capable of degrading PHB under a wide range of natural/ lab conditions.


Synthesis and in vitro antimalarial activity of sulfone endoperoxides.
A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3-dioxabicyclo[3.3.1]+ ++nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and alkylation and acylation of a sterically hindered tertiary alcohol compatible with the endoperoxy functionality. Some of compounds 4, which are structurally related to yingzhaosu A (2), were found to exhibit in vitro antimalarial activity comparable to that of artemisinin (1) and superior to that of arteflene (3).


Remember and know judgments during recognition in chronic schizophrenia.
Deficits in learning and memory are among the most robust correlates of schizophrenia. It has been hypothesized that these deficits are in part due to reduced conscious recollection and increased reliance on familiarity assessment as a basis for retrieval. The Remember-Know (R-K) paradigm was administered to 35 patients with chronic schizophrenia and 35 healthy controls. In addition to making "remember" and "know" judgments, the participants were asked to make forced-choice recognition judgments with regard to details about the learning episode. Analyses comparing response types showed a significant reduction in "remember" responses and a significant increase in "know" responses in schizophrenia patients relative to controls. Both patients and controls recalled more details of the learning episode for "remember" compared to "know" responses, although, in particular for "remember" responses, patients recalled fewer details compared with controls. Notably, patients recognized fewer inter-item but not intra-item stimulus features compared with controls. These findings suggest deficits in organizing and integrating relational information during the learning episode and/or using relational information for retrieval. A Dual-Process Signal Detection interpretation of these findings suggests that recollection in chronic schizophrenia is significantly reduced, while familiarity is not. Additionally, a unidimensional Signal Detection Theory interpretation suggests that chronic schizophrenia patients show a reduction in memory strength, and an altered criterion on the memory strength distribution for detecting new compared with old stimuli but not for detecting stimuli that are remembered versus familiar. Taken together, these findings are consistent with a deficit in recollection and increased reliance on familiarity in making recognition memory judgments in chronic schizophrenia.


Budding uninhibited by benzimidazoles 1 promotes cell proliferation, invasion, and epithelial-mesenchymal transition via the Wnt/β-catenin signaling in glioblastoma.
The pathogenesis and progression of GBM (glioblastoma), as one of the most frequently occurring malignancies of the central nervous system, are regulated by several genes. BUB1 (budding uninhibited by benzimidazoles 1) is a mitotic checkpoint that plays an important role in chromosome segregation as well as in various tumors. However, its role in glioma is unknown. The current study discovered prominently elevated BUB1 in glioma and a significant relationship between BUB1 expression, a high World Health Organization grade, and a poor prognosis in glioma patients. Moreover, BUB1 triggered EMT (epithelial-mesenchymal transition) apart from promoting glioma cell proliferation, migration, and infiltration. Besides, BUB1 promoted EMT by activating the Wnt/β-catenin axis. As implied by our study, BUB1 probably has the potential as a target for GBM management.


[Thyroid autoimmunity in type I (insulin dependent) diabetes mellitus].
225 diabetic children aged 4-18 years, were screened for antithyroid antibodies. 120 of them were determined at onset of diabetes mellitus. In the remaining patients, duration of diabetes ranged from 6 months to 8 years. The overall prevalence of thyroid antibodies was 14.19% (21/148), while positive titres were found in 10.39% (8/77), at onset. Chronic lymphocytic thyroiditis was diagnosed in 16 patients. No growth retardation was observed. Thyroxine therapy was started in all hypothyroid cases. We conclude that antithyroid antibodies screening in well indicated in diabetic children in view of their high prevalence and strong association with chronic thyroiditis.


Islet cell tumors of the pancreas.
Pancreatic endocrine neoplasms are a heterogeneous group of tumors that produce active hormones and result in distinct clinical syndromes. For the most part, they are malignant and require sophisticated diagnostic and localization techniques in order to identify their presence. Delays in diagnosis are the rule rather than the exception. Improvements in the diagnosis of gastrinomas and insulinomas appear to result in an increase in resectability rates. The widespread availability of intraoperative ultrasonography, as well as improved knowledge of the location of these tumors, has also had an impact on improved cure rates. With heightened awareness of these syndromes, increasing numbers of patients can be identified and more effective treatments developed for the refractory and recurrent tumors.


MR properties of 19 F C3 F8 gas in the lungs of healthy volunteers: T 2 ∗ and apparent diffusion coefficient at 1.5T and T 2 ∗ at 3T.
To measure the transverse relaxation time ( T 2 ∗ ) and apparent diffusion coefficient (ADC) of 19 F-C3 F8 gas in vivo in human lungs at 1.5T and 3T, and to determine the representative distribution of values of these parameters in a cohort of healthy volunteers. Mapping of ADC at lung inflation levels of functional residual capacity (FRC) and total lung capacity (TLC) was performed with inhaled 19 F-C3 F8 (eight subjects) and 129 Xe (six subjects) at 1.5T. T 2 ∗ mapping with 19 F-C3 F8 was performed at 1.5T (at FRC and TLC) for 8 subjects and at 3T (at TLC for seven subjects). At both FRC and TLC, the 19 F-C3 F8 ADC was smaller than the free diffusion coefficient demonstrating airway microstructural diffusion restriction. From FRC to TLC, the mean ADC significantly increased from 1.56 mm2 /s to 1.83 mm2 /s (P = .0017) for 19 F-C3 F8, and from 2.49 mm2 /s to 3.38 mm2 /s (P = .0015) for 129 Xe. The posterior-to-anterior gradient in ADC for FRC versus TLC in the superior half of the lungs was measured as 0.0308 mm2 /s per cm versus 0.0168 mm2 /s per cm for 19 F-C3 F8 and 0.0871 mm2 /s per cm versus 0.0326 mm2 /s per cm for 129 Xe. A consistent distribution of 19 F-C3 F8 T 2 ∗ values was observed in the lungs, with low values observed near the diaphragm and large pulmonary vessels. The mean T 2 ∗ across volunteers was 4.48 ms at FRC and 5.33 ms at TLC for 1.5T, and 3.78 ms at TLC for 3T. In this feasibility study, values of physiologically relevant parameters of lung microstructure measurable by MRI ( T 2 ∗ , and ADC) were established for C3 F8 in vivo lung imaging in healthy volunteers.


[Congenital factor VII deficiency revealed by post-circumcision bleeding].
Factor VII formerly known as proconvertin is a vitamin K-dependent coagulation factor involved in exogenous coagulation. Congenital factor VII deficiency is a very rare autosomal recessive hereditary disease. We report the case of a new-born of parents who had first-degree consanguinity, admitted to hospital on D10 of life with post-circumcision haemorrhagic syndrome. Laboratory tests showed decreased levels of prothrombin and normal activated partial thromboplastin time. Coagulation tests showed isolated factor VII deficiency to 18%. The new-born received transfusion of packed red blood cells and fresh frozen plasma in order to stop bleeding with favorable outcome. This study highlights the features of this rare deficit. Prognosis is linked to the risk of severe bleedings, such as brain bleeding occurring in the neonatal period as is the case with our patient. Hence the need to perform blood crasis assessment before circumcision.


TC10β/CDC42 GTPase activating protein is required for the growth of cortical neuron dendrites.
Neuronal morphogenesis plays an important role in neuronal development. TC10β/CDC42 GTPase-activating protein (TCGAP) is known to be a brain-enriched multiple domain protein, but its role in neuronal development process remains poorly understood. In the present study, we showed that TCGAP positively regulated dendritic outgrowth and spine formation in developing cortical neurons. Knocking down TCGAP by RNA interference led to a decrease in the overall length of dendrite arbors and the number of dendrite branches both in vitro and in vivo. Overexpressing TCGAP in cultured cortical neurons increased dendritic outgrowth and branching. Moreover, overexpressing TCGAP lead to an increase of spine density while knocking-down TCGAP decreased spine density in vivo. The defect by downregulating TCGAP could be rescued by expressing a knock-down resistant form of TCGAP both in vivo and in vitro. In contrast, neither downregulating nor overexpressing TCGAP had any effect on axonal morphogenesis in primary cortical neuron cultures. Together, our findings suggest that TCGAP regulates neuronal morphogenesis in developing cortical neurons at both early and late stage.


Effect of PM2.5 on macrosomia in China: A nationwide prospective cohort study.
Macrosomia is associated with both neonatal complications and adult diseases (obesity, diabetes mellitus, etc.). Previous studies have reported maternal exposure to PM2.5 might influence metabolism and fetal development and cause adverse pregnancy outcomes. Studies conducted in areas with low PM2.5 concentration have found relationship between gestational PM2.5 exposure and birth weight. However, the impact of air pollution on macrosomia has not been studied, especially in highly polluted areas. To evaluate the association between fine particulate matter (PM2.5) exposure during pregnancy and the risk of macrosomia. Data from preconception health examination and prenatal and postnatal records were collected from 1 January 2010 to 31 December 2012 in the National Free Preconception Health Examination Project. Monthly mean of PM2.5 concentration during pregnancy was estimated from satellite data using an ensemble machine learning model. A newborn with birth weight above 4000 g was defined as macrosomia. Logistic regression models were used to examine the association between maternal exposure to PM2.5 and the risk of macrosomia, after adjusting for maternal age, pre-pregnancy body mass index, parity, neonatal sex, duration of gestation, seasonality, educational level, smoking and drinking habits, past history of diabetes mellitus and hypertension, and family history of diabetes mellitus. Restricted cubic spline models were used to evaluate the dose-response relationship between the risk of macrosomia and PM2.5 concentration. Of 177 841 singleton nonlow birth weight newborns included, 14 598 (8.2%) had macrosomia. The mean PM2.5 concentrations were 70.7, 71.5, and 80.9 μg/m3 in the first, second, and third trimesters. In full-adjusted logistic regression models, significant associations were found between increased risk of macrosomia and every 10 μg/m3 increase of PM2.5 concentration over the first (odds ratio [OR]: 1.045; 95% CI, 1.037-1.052), second (OR: 1.035; 95% CI, 1.028-1.043), and third (OR: 1.033; 95% CI, 1.026-1.039) trimesters. There was a nonlinear does-response association between PM2.5 concentration and the risk of macrosomia. Maternal exposure to PM2.5 during pregnancy was associated with an increased risk of macrosomia in China.


Analysis of polymerase chain reaction-product by capillary electrophoresis with laser-induced fluorescence detection and its application to the diagnosis of medium-chain acyl-coenzyme A dehydrogenase deficiency.
Capillary gel electrophoresis with laser-induced fluorescence (CGE-LIF) has been developed to detect polymerase chain reaction (PCR) amplified samples. LIF detection was performed using Thiazole Orange as the fluorescent intercalating dye. This method was ca. 100x as sensitive as that with UV detection. The highly sensitive CGE-LIF was applied to the detection of the most prevalent mutation (lysine329-to-glutamic acid substitution) in medium-chain acyl-coenzyme A dehydrogenase (MCAD) deficiency. The disorder, which shows an autosomal recessive inheritance, is known to be highly prevalent among Caucasian population and often mimics as Reye-like syndrome or sudden infant death. A DNA fragment containing the mutation site was PCR-amplified with two sets of allele specific oligonucleotide primers, followed by CGE-LIF. The mutant allele produced a 175-base pairs DNA fragment, which the normal allele generated a 202-base pairs DNA fragment. CGE-LIF clearly distinguished these PCR products, facilitating rapid diagnosis of MCAD deficiency.


Neutropenia, granulocytic hypersegmentation and coeliac disease.
A 7-year-old girl was admitted to hospital with a 2-month history of profound weakness. Anaemia, marked neutropenia and hypersegmentation of the granulocytes were the major laboratory findings. These abnormal haematological data were due to significant folate deficiency caused by active coeliac disease diagnosed by both the presence of antigliadin and endomysium antibodies and typical histological features of the small intestine. The haematological abnormalities resolved within 3 weeks following a gluten-free diet and iv supplementation of folic acid.


Antibacterial peptide PMAP-37(F34-R), expressed in Pichia pastoris, is effective against pathogenic bacteria and preserves plums.
Recently, researchers have focused on the search for alternatives to conventional antibiotics. Antimicrobial peptides are small bioactive peptides that regulate immune activation and have antibacterial activity with a reduced risk of bacterial resistance. Porcine myeloid antibacterial peptide 37 (PMAP-37) is a small-molecule peptide with broad-spectrum antibacterial activity isolated from pig bone marrow, and PMAP-37(F34-R) is its analogue. In this study, PMAP-37(F34-R) was recombinantly expressed in Pichia pastoris, and the recombinant peptide was further investigated for its antibacterial properties, mechanism and preservative in plums. To obtain a Pichia pastoris strain expressing PMAP-37(F34-R), we constructed a plasmid expressing recombinant PMAP-37(F34-R) (pPICZα-PMAP-37(F34-R)-A) and introduced it into Pichia pastoris. Finally, we obtained a highly active recombinant peptide, PMAP-37(F34-R), which inhibited the activity of both Gram-positive and Gram-negative bacteria. The minimum inhibitory concentration is 0.12-0.24 µg/mL, and it can destroy the integrity of the cell membrane, leading to cell lysis. It has good stability and is not easily affected by the external environment. Hemolysis experiments showed that 0.06 µg/mL-0.36 µg/mL PMAP-37(F34-R) had lower hemolysis ability to mammalian cells, and the hemolysis rate was below 1.5%. Additionally, 0.36 µg/mL PMAP-37(F34-R) showed a good preservative effect in plums. The decay and weight loss rates of the treated samples were significantly lower than those of the control group, and the respiratory intensity of the fruit was delayed in the experimental group. In this study, we constructed a recombinant Pichia pastoris strain, which is a promising candidate for extending the shelf life of fruits and has potential applications in the development of new preservatives.


Community social capital and the health-related quality of life among empty-nest elderly in western China: moderating effect of living arrangements.
At present, the empty nest phenomenon is becoming more and more serious in the world, especially in China, and its health problems deserve attention. Therefore, the purpose of this study is to explore the impact of community social capital on the health-related quality of life of empty-nest elderly. The study used data collected from a survey study conducted between 2018 and 2019 in Sichuan province, China, with 638 empty-nest elderly meeting our criteria. SF-12 scale and self-made social capital scale were used to evaluate the health-related quality of life and community social capital of empty-nest elderly. Through descriptive statistical analysis, bivariate analysis and hierarchical multiple regression model, this study analyzes the relationship between community social capital and health-related quality of life of empty-nest elderly. Considering the role of living arrangements, this study further uses the simple effect analysis method to explore the moderating role of living arrangements. After controlling the relevant variables, the cognitive social capital (CSC) of empty-nest elderly had a positive relationship with the physical health summary (PCS) (β = 0.188, p<0.001) and mental health summary (MCS) (β = 0.205, p<0.001). No effect of structural social capital on quality of life was found as a result. Living arrangements played a moderation effect on the relationship between CSC and MCS (β=-2.018, p<0.05). The MCS score of high CSC group (55.516 ± 0.757) was significantly higher than that of low CSC group (49.383 ± 0.722). The results suggest empty-nest elderly has poorer physical health and weaker structural social capital, while the cognitive social capital has a greater positive impact on their quality of life. Targeted interventions to enhance community social capital may be beneficial to improve health status of this vulnerable population.


Evaluating enhanced pulse oximetry auditory displays for neonatal oxygen targeting: A randomized laboratory trial with clinicians and non-clinicians.
Standard pulse oximeter auditory tones do not clearly indicate departures from the target range of oxygen saturation (SpO2) of 90%-95% in preterm neonates. We tested whether acoustically enhanced tones would improve participants' ability to identify SpO2 range. Twenty-one clinicians and 23 non-clinicians used (1) standard pulse oximetry variable-pitch tones plus alarms; (2) beacon-enhanced tones without alarms in which reference tones were inserted before standard pulse tones when SpO2 was outside target range; and (3) tremolo-enhanced tones without alarms in which pulse tones were modified with tremolo when SpO2 was outside target range. For clinicians, range identification accuracies (mean (SD)) in the standard, beacon, and tremolo conditions were 52% (16%), 73% (14%) and 76% (13%) respectively, and for non-clinicians 49% (16%), 76% (13%) and 72% (14%) respectively, with enhanced conditions always significantly more accurate than standard. Acoustic enhancements to pulse oximetry clearly indicate departures from preterm neonates' target SpO2 range.


Immunoaffinity chromatography in antivenomics studies: Various parameters that can affect the results.
Antivenomics is a recently developed powerful method for the study of antivenom antibody profiles when bound to homologous and heterologous snake venoms. The information obtained is useful in gaining an understanding of venom protein immunogenicity, antivenom potency and also for the improvement of antivenom potency and paraspecificity. The preferred method used in this type of study is immunoaffinity chromatography of the venom proteins on an antivenom IgG (or F(ab')2) column where the bound and unbound proteins can be separated and identified. However, there are some parameters of the immunochromatography that can significantly affect the binding of the proteins to the immunoaffinity matrix and lead to imprecise results in antivenom immunoprofiling. The present study demonstrated that the ligand density (mg IgG/ml of the matrix), the buffers used for binding and washing the venom proteins, the amount of venom loaded, the abundance of some venom protein(s) and the eluting buffers can significantly alter the binding of the proteins to the matrix and consequently the conclusions drawn from antivenomics studies. Furthermore, the immunochromatographic procedure can be extended to include the estimation of the relative affinity of venom protein-antibody interactions that can provide additional information useful to antivenomics study.


Long term perifusion of rabbit ovarian follicles.
Preovulatory follicles were dissected from ovaries of estrous rabbits. Four follicles were placed in each chamber of a perifusion system. Medium 199, containing 10% rabbit serum and antibiotics, eluted through the chambers at a rate of 1 ml/10 min. Every 6 h for 36 h, 1 microgram of LH and 50 ng of FSH were injected into each chamber. P4, T and E2 were measured in the medium. P4 exhibited a peak after each of the injections at 6, 12, 18, 24 and 30 h. E2 and T gave major peaks after the injection at 0 time, with minor peaks after the injection at 6 h; thereafter T and E2 secretion gradually decreased to levels below those of baseline.


Avian NK activities, cells and receptors.
Natural killer (NK) activity has been examined in birds for over 30 years, but evidence that avian NK activity plays crucial roles in disease is only suggestive. In chickens, NK activity is mediated by TCR0 cells in the intestinal epithelium, but elsewhere subsets of alphabeta and gammadelta T cells (NKT cells) may be more important. There are few lectin-like NK receptor genes, located in the genomic region syntenic with the natural killer complex (NKC) as well as the major histocompatibility complex (MHC). In contrast, a huge number of Ig-like receptor genes are located in a region syntenic with the leukocyte receptor complex (LRC).


Prepregnancy habitual intake of vitamin D from diet and supplements in relation to risk of gestational diabetes mellitus: A prospective cohort study.
Vitamin D may play a pivotal role in regulating insulin secretion and insulin sensitivity. However, the effect of vitamin D intake, either from the diet or from supplements, on the development of gestational diabetes mellitus (GDM) remains unclear. We prospectively examined the association of prepregnancy habitual intake of vitamin D from diet and supplements with the risk of incident GDM in a well-established cohort. The present study was performed on 21 356 singleton pregnancies from 15 225 women in the Nurses' Health Study II cohort. Diet information, including vitamin D intake from food sources and supplements, was assessed in 1991 and every 4 years thereafter by validated food frequency questionnaires. Log-binomial models with generalized estimating equations were used to estimate relative risks (RRs) and 95% confidence intervals (CIs). During 10 years of follow-up, 865 incident GDM cases were documented. After adjustment for age, parity, race/ethnicity, family history of diabetes, dietary and lifestyle factors, and body mass index, the RRs (95% CIs) of GDM risk associated with supplemental vitamin D intake of 0, 1-399, and ≥400 IU/day were 1.00 (reference), 0.80 (0.67-0.96), and 0.71 (0.56-0.90), respectively (Ptrend = 0.002). Dietary and total vitamin D intakes were also inversely associated with GDM risk, but the associations were not statistically significant. Prepregnancy supplemental vitamin D intake was significantly and inversely associated with risk of GDM. This study indicates potential benefits of increasing vitamin D intake from supplements in the prevention of GDM in women of reproductive age.


Identification of GLA gene deletions in Fabry patients by Multiplex Ligation-dependent Probe Amplification (MLPA).
Fabry disease is an under-recognized X-linked lysosomal disorder, due to alpha-galactosidase A deficiency. Most of the mutations in the GLA gene are detectable using genomic sequencing analysis. However, deletions of one or more exons or deletion encompassing the entire gene are undetectable, especially in heterozygous females. The Multiplex Ligation-dependent Probe Amplification (MLPA) is an efficient tool for discovering these rearrangements. In this study two novel different deletions were detected using MLPA assay on two Fabry patients, both resulted mutation negative by sequencing analysis. These data suggest that this screening should be systematically included in genetic testing surveys of patients with Fabry disease.


The association of allopurinol with persistent physical disability and frailty in a large community based older cohort.
The protective effects of allopurinol on physical function in older adults are not well understood, despite its potential to improve functional gains and reduce sarcopenia. This study aims to determine the association between allopurinol, persistent physical disability, and frailty in older gout patients. This analysis used data from a randomized trial in an older cohort, ASPirin in Reducing Events in the Elderly (ASPREE). ASPREE recruited 19,114 participants aged ≥65 years without prior cardiovascular events, dementia, or independence-limiting physical disability at trial enrolment. This analysis examined the association of baseline and time-varying allopurinol use with persistent physical disability and new-onset frailty in participants with gout at baseline (self-report or use of any anti-gout medications). Frailty was measured using the Fried frailty phenotype (score ≥3/5) and a deficit accumulation frailty index (FI) (score >0.21/1.0). Multivariable Cox proportional-hazards models were used for main analyses. This analysis included 1155 gout participants, with 630 taking allopurinol at baseline and 525 not. During a median follow-up of 5.7 years, 113 new allopurinol users were identified. Compared with nonusers, baseline allopurinol use was associated with a significant risk reduction of persistent physical disability (Adjusted HR 0.46, 95% CI 0.23-0.92, p = 0.03). The strength of the association was modestly attenuated in the time-varying analysis (Adjusted HR 0.56, 0.29-1.08, p = 0.08). No significant associations with frailty measures were observed for either baseline allopurinol use (Fried frailty: Adjusted HR 0.83, 0.62-1.12; FI: Adjusted HR 0.96, 0.74-1.24) or time-varying allopurinol use (Fried frailty: Adjusted HR 0.92, 0.69-1.24; FI: Adjusted HR 1.02, 0.78-1.33). Allopurinol use in older adults with gout is associated with a reduced risk of persistent physical disability but not associated with risk of frailty.


An Outbreak of Clostridium (Clostridioides) difficile Infections within an Acute and Long-Term Care Wards Due to Moxifloxacin-Resistant PCR Ribotype 176 Genotyped as PCR Ribotype 027 by a Commercial Assay.
We aimed to characterize Clostridioides difficile isolates cultured during a six-month single-center study from stool samples of patients with C. difficile infection (CDI) genotyped by the Xpert®C. difficile/Epi assay by polymerase chain reaction (PCR) ribotyping, toxin genes' detection and multi-locus variable number tandem repeats analysis (MLVA). The susceptibility to metronidazole, vancomycin and moxifloxacin was determined by agar dilution. In addition, the presence of Thr82Ile in the GyrA and a single nucleotide deletion at position (Δ117) in the tcdC gene were investigated. Between January 1 and June 30, 2016, of 114 CDIs, 75 cases were genotyped as presumptive PCR ribotype (RT) 027 infections using a commercial assay. C. difficile isolates cultured from presumptive RT027 stool samples belonged to RT176. These isolates carried genes for toxin A (tcdA), B (tcdB), binary (cdtA/B) and had Δ117 in the tcdC gene. Using MLVA, the 71/75 isolates clustered into two clonal complexes (CCs). Of these, 39 isolates (54.9%) were from patients hospitalized in acute care and 32 isolates (45.1%) were isolated from patients hospitalized in the long-term care department. All isolates were susceptible to metronidazole and vancomycin, and 105 isolates were resistant to moxifloxacin (92%) carrying Thr83Ile in the GyrA. An outbreak of RT176 CDIs, suspected as RT027, was recognized in a Slovakian hospital. In order to monitor the emergence and spread of RT027-variants, the identification of a presumptive RT027 CDI should be confirmed at a strain level by PCR ribotyping.


Cervical cytology screening practices among obstetrician-gynecologists.
To estimate the current cervical cytology screening practices of American College of Obstetricians and Gynecologists (ACOG) Fellows, to establish a baseline for tracking future changes in practice. Questionnaires were mailed to a random sample of ACOG Fellows (n = 599) and to a group of Fellows who have regularly participated in past ACOG surveys (n = 409). The questionnaires asked about current cytology screening and evaluation practices and presented clinical practice vignettes with additional questions. Descriptive statistical methods were used to evaluate the responses. Questionnaires were returned by 651 physicians (64.6%); 624 were complete. More than 94% of the respondents start cytology testing at age 18 years. Almost three fourths (74.2%) continue screening indefinitely. More than 80% use a liquid-based method of collection. Almost two thirds (65.1%) order human papillomavirus testing occasionally, usually (81.9%) for reports of atypical squamous cells of undetermined significance (ASCUS). Most Fellows in the sample perform colposcopy for an ASCUS result. Reports of atypical glandular cells resulted in variable approaches to further evaluation. Patient age and history were important variables for all test reports. Legal concerns were mentioned as important determinants of practice patterns. In this sample of ACOG Fellows, most perform cervical cytology and evaluate abnormal results in accord with guidelines in place before the recommended changes in screening and evaluation were published in 2003.


Immunogenic and antigenic epitopes of immunoglobulins--VII. The topographical distribution of Fc gamma epitopes and the relationship of an iso-allotypic specificity to the presence of histidine 435.
Epitopes recognised by a panel of 23 anti-Fc gamma monoclonal antibodies (McAbs) have been subdivided into three groups each having a distinct topographical distribution. One group of mutually inhibitory McAbs are reactive with epitopes expressed on the fy "surface" of the C gamma 2 domain. A second group recognises epitopes in the region of arginine 355 of the C gamma 3 domain whilst the third group recognises epitopes expressed in the inter C gamma 2/C gamma 3 domain region--as evidenced by inhibition of Staphylococcus aureus protein A binding. An antibody of the latter group reactive with IgG1, 2, 4 and IgG3m(15,16) proteins but not IgG3m(5) or IgG3m(21) proteins allows histidine 435 to be identified as a critical residue for expression of the epitope recognised by this antibody.


Diffusion-controlled association of a dye, 1-anilinonaphthalene-8-sulfonic acid, to a protein, bovine serum albumin, using a fast-flow microsecond mixer and stopped-flow.
The kinetic constants of the two fastest reactions of 1-anilinonaphthalene-8-sulfonic acid binding to bovine serum albumin are derived from the results of experiments with a microsecond fast-flow mixing technique and a stopped-flow method. The experiments are interpreted in terms of rapid bimolecular diffusion-controlled associations to two independent regions on the protein surface; this reaction mechanism contrasts with previous kinetic studies of ligand binding to bovine serum albumin which have not demonstrated the fastest kinetic processes.


Inhibition of voltage-gated Na(+) current by nanosecond pulsed electric field (nsPEF) is not mediated by Na(+) influx or Ca(2+) signaling.
In earlier studies, we found that permeabilization of mammalian cells with nsPEF was accompanied by prolonged inhibition of voltage-gated (VG) currents through the plasma membrane. This study explored if the inhibition of VG Na(+) current (I(Na)) resulted from (i) reduction of the transmembrane Na(+) gradient due to its influx via nsPEF-opened pores, and/or (ii) downregulation of the VG channels by a Ca(2+)-dependent mechanism. We found that a single 300 ns electric pulse at 1.6-5.3 kV/cm triggered sustained Na(+) influx in exposed NG108 cells and in primary chromaffin cells, as detected by increased fluorescence of a Sodium Green Dye. In the whole-cell patch clamp configuration, this influx was efficiently buffered by the pipette solution so that the increase in the intracellular concentration of Na(+) ([Na](i)) did not exceed 2-3 mM. [Na](i) increased uniformly over the cell volume and showed no additional peaks immediately below the plasma membrane. Concurrently, nsPEF reduced VG I(Na) by 30-60% (at 4 and 5.3 kV/cm). In control experiments, even a greater increase of the pipette [Na(+)] (by 5 mM) did not attenuate VG I(Na), thereby indicating that the nsPEF-induced Na(+) influx was not the cause of VG I(Na) inhibition. Similarly, adding 20 mM of a fast Ca(2+) chelator 1,2-bis(o-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid (BAPTA) into the pipette solution did not prevent or attenuate the inhibition of the VG I(Na) by nsPEF. These findings point to possible Ca(2+)-independent downregulation of the VG Na(+) channels (e.g., caused by alteration of the lipid bilayer) or the direct effect of nsPEF on the channel.


Influence of clofibrate on blood viscosity in primary hyperlipoproteinemia.
In patients with primary hyperlipoproteinemia (23 patients type II a and II b, 13 patients type IV), changes in lipoprotein concentrations (lipid fraction), fibrinogen concentrations, in kinematic serum and plasma viscosity (determined by means of a capillary viscosimeter) and changes in relative apparent viscosity at shear rate 46 s-1 and 115 s-1 (determined by means of a plate-cone-viscosimeter) were measured before and after a clofibrate therapy (2 X 1 g/day) lasting for 7 to 9 weeks. Serum and plasma viscosity was lowered significantly in both types II and IV. The apparent viscosity decreased at shear rate 46 s-1 in type IV, whereas it remained unchanged in type II. Moreover, there exists a qualitative correlation between changes in serum viscosity and changes in lipoprotein concentration. Fibrinogen concentration remained unaltered.


Mutation of the conserved Asp-Asp pair impairs the structure, function, and inhibition of CTX-M Class A β-lactamase.
The Asp233-Asp246 pair is highly conserved in Class A β-lactamases, which hydrolyze β-lactam antibiotics. Here, we characterize its function using CTX-M-14 β-lactamase. The D233N mutant displayed decreased activity that is substrate-dependent, with reductions in kcat /Km ranging from 20% for nitrocefin to 6-fold for cefotaxime. In comparison, the mutation reduced the binding of a known reversible inhibitor by 10-fold. The mutant structures showed movement of the 213-219 loop and the loss of the Thr216-Thr235 hydrogen bond, which was restored by inhibitor binding. Mutagenesis of Thr216 further highlighted its contribution to CTX-M activity. These results demonstrate the importance of the aspartate pair to CTX-M hydrolysis of substrates with bulky side chains, while suggesting increased protein flexibility as a means to evolve drug resistance.


Plasma adiponectin levels predict cognitive decline and cortical thinning in mild cognitive impairment with beta-amyloid pathology.
Blood adiponectin and leptin are adipokines that emerged as potential biomarkers for predicting Alzheimer's disease (AD) owing to their strong connection with obesity. Although obesity affects the relation between beta-amyloid (Aβ) aggregation and cognitive decline, the longitudinal interactive effect of adipokines and Aβ on cognition and brain structures in humans remains unexplored. Hence, we investigated whether plasma levels of adiponectin and leptin are associated with future cognitive decline and cortical thinning across Aβ conditions (Aβ [+] and Aβ [-]) in individuals with mild cognitive impairment (MCI). Of 156 participants with MCI from the longitudinal cohort study of Alzheimer's Disease Neuroimaging Initiative (ADNI), 31 were Aβ (-) and 125 were Aβ (+) as determined by CSF analysis. The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores and the thickness of the parahippocampal and entorhinal cortices were used to evaluate cognition and brain structure, respectively. After stratifying groups by Aβ conditions, the association of cognitive and brain structural changes with baseline plasma levels of adiponectin and leptin was examined. Of the total 156 participants, 51 were women (32.7%). The mean age of participants was 74.5 (standard deviation 7.57), and the mean follow-up period was 54.3 months, without a difference between the Aβ (+) and (-) groups. After adjustment for confounders, higher plasma adiponectin levels were associated with a faster increase in ADAS-Cog scores, indicating faster cognitive decline under the Aβ (+) condition (beta = 0.224, p = 0.018). Likewise, participants with higher plasma adiponectin presented faster cortical thinning in the bilateral parahippocampal cortices under the Aβ (+) condition (beta = - 0.004, p = 0.012 for the right side; beta = - 0.004, p = 0.025 for the left side). Interestingly, plasma adiponectin levels were not associated with longitudinal ADAS-Cog scores or cortical thickness in the Aβ (-) condition. Plasma leptin levels were not predictive of cognition or cortical thickness regardless of Aβ status. Plasma adiponectin can be a potential biomarker for predicting the speed of AD progression in individuals with Aβ (+) MCI.


Tuberculosis of the pyriform fossa--a rare entity.
Tuberculosis of the pharynx is less common than tuberculosis of the larynx. We present a rare case of tuberculosis of the pyriform fossa which clinically masqueraded as a malignancy. Our patient showed a prompt improvement in symptoms after commencing antitubercular treatment.


Control of mesenchymal lineage progression by microRNAs targeting skeletal gene regulators Trps1 and Runx2.
Multiple microRNAs (miRNAs) that target the osteogenic Runt-related transcription factor 2 (RUNX2) define an interrelated network of miRNAs that control osteoblastogenesis. We addressed whether these miRNAs have functional targets beyond RUNX2 that coregulate skeletal development. Here, we find that seven RUNX2-targeting miRNAs (miR-23a, miR-30c, miR-34c, miR-133a, miR-135a, miR-205, and miR-217) also regulate the chondrogenic GATA transcription factor tricho-rhino-phalangeal syndrome I (TRPS1). Although the efficacy of each miRNA to target RUNX2 or TRPS1 differs in osteoblasts and chondrocytes, each effectively blocks maturation of precommitted osteoblasts and chondrocytes. Furthermore, these miRNAs can redirect mesenchymal stem cells into adipogenic cell fate with concomitant up-regulation of key lineage-specific transcription factors. Thus, a program of multiple miRNAs controls mesenchymal lineage progression by selectively blocking differentiation of osteoblasts and chondrocytes to control skeletal development.


Enhanced HIV-1 replication in V beta 12 T cells due to human cytomegalovirus in monocytes: evidence for a putative herpesvirus superantigen.
HIV-1 replicates more efficiently in cultured IL-2-dependent CD4 T cells expressing V beta 12 T cell receptors (TCRs) rather than other TCRs (Laurence et al., 1992). A viral reservoir is frequently established in V beta 12 T cells in HIV-1-infected patients. Here we show that cytomegalovirus (CMV) is responsible for V beta 12-selective HIV-1 replication that is indistinguishable from the effect of known superantigens (SAGs). This effect is dependent on direct contact of T cells with CMV-infected monocytes. CMV infection, but not ie1 or ie2 transfection, reproduces this effect in a monocytoid cell line (U937). In HIV-infected patients, the presence of CMV antibodies correlates with an HIV-1 viral load preferentially skewed to the V beta 12 subset. Together, these data suggest that a CMV gene product is responsible for a SAG-driven V beta 12-selective HIV-1 reservoir in vivo.


Comprehensive study of the parameters influencing the detection of organotin compounds by a pulsed flame photometric detector in sewage sludge.
An investigation of the operating conditions of a pulsed flame photometric detection (PFPD) system for the determination of organotin compounds (OTCs) in sewage sludge is reported. During the analyses, some spectral interferences were observed. For their elimination detector parameters such as gate delay and gate width were investigated. In addition, the applicability of three different internal standards was evaluated. Under optimised analytical conditions (gate delay 3 ms, gate width 2 ms, tripropyltin as internal standard) limits of detection (LOD) were determined. The LOD for butyltins ranged between 8 and 16 ng Sn g(-1), for phenyltins around 8 ng Sn g(-1) and for octyltins between 5 and 10 ng Sn g(-1). Since there is no certified reference material (CRM) available for sewage sludge, the accuracy of the analytical procedure was checked by the analysis of CRM PACS-2 (marine sediment) and a spiked sludge sample. Good agreement between determined and certified values was obtained. Sewage sludge from a local wastewater treatment plant was analysed and the results compared with data from the literature.


Carcinogenicity of dextran sulfate sodium in relation to its molecular weight.
The carcinogenicity of dextran and 3 kinds of dextran sulfate sodium with different molecular weights and almost the same sulfur content were compared in ACI rats. Dextran sulfate sodium of molecular weight 54,000 showed a strong carcinogenic activity when it was given orally as 2.5% diet, whereas dextran sulfate sodium of molecular weight 520,000 and 9500 and dextran showed no significant carcinogenicity, i.e. the peak of carcinogenic activity of dextran sulfate sodium appeared at molecular weight 54,000, and dextran sulfates with larger or smaller molecular weights had no carcinogenic activity.


Multi-enzyme-targeted chemotherapy by acivicin and actinomycin.
On the basis of our observation of the increased specific activities of glutamine-utilizing enzymes in purine and pyrimidine metabolism in hepatoma 3924A, and because the concentration of glutamine is ten times lower in the hepatomas than in the liver, the biochemical pharmacology of the anti-glutamine agent, acivicin, was examined. (1) Acivicin competitively inhibited the activities of amidophosphoribosyl-transferase, CTP synthetase and carbamoyl-phosphate synthetase II from extracts of liver and hepatoma 3924A. (2) In addition to the competitive inhibition exerted by acivicin, evidence was obtained that this drug also irreversibly inactivated in vitro the glutamine-utilizing enzymes. It is particularly relevant for the selectivity of acivicin that the activity of aspartate carbamoyltransferase, an enzyme present in the same complex as carbamoyl-phosphate synthetase II, was not affected by the anti-glutamine agent. (3) Acivicin in vivo brought down the activities of glutamine-utilizing enzymes in a period of 10 min to 1 hr after injection. CTP synthetase activity declined to less than 10% of that observed in the uninjected rats. The decreases were not reversible by various in vitro methods, but in vivo the activities returned to normal range in 72 hr. (4) The activity of aspartate carbamoyltransferase, which exists as a multi-enzyme complex with synthetase II, was not altered by acivicin injection. Similar results were observed in transplantable sarcoma in the rat. (5) The acivicin-induced decrease in enzymic activities could not be restored by purification of the enzymes. (6) In vitro studies indicated that addition of acivicin to liver or hepatoma extracts or purified enzymes rapidly decreased enzymic activities; the activities could not be restored. These results are consistent with an interpretation that acivicin acts either as a tight-binding inhibitor or as an inactivator through alkylation of the enzymes of glutamine utilization. (7) Acivicin in combination with actinomycin provided a synergistic kill of hepatoma cells in tissue culture and also inhibited the growth of transplantable solid hepatoma 3924A in the rat. (8) The synergistic biological results of combination chemotherapy with acivicin and actinomycin can be accounted for by the action of acivicin in inhibiting GMP and CTP synthetases, resulting in a decrease in GTP and CTP content, and by the actinomycin-caused inhibition of RNA polymerase in selectively blocking the utilization of GTP and CTP.


Differences in diet pattern adherence by nativity and duration of US residence in the Mexican-American population.
Literature on the diet of the Mexican-American population suggests that food consumption differs by nativity and duration of residence in the United States. However, no studies have used dietary pattern analysis to investigate these differences. To create dietary patterns, we used principal components analysis on food frequency questionnaire data for all adult respondents of the National Health and Nutrition Examination Survey years 2003-2006. Four dietary patterns were identified: Western, Healthy, Tomato/Tortilla, and Coffee/Sugar. Least squares means regression was used to test differences in adjusted mean dietary adherence scores among Mexico-born Mexican-American adults residing in the United States for <15 years (n=302), Mexico-born Mexican-American adults residing in the United States for ≥15 years (n=234), US-born Mexican-American adults (n=509), and US-born non-Hispanic whites (n=2,530) aged 18 to 69 years. Mean score for each diet pattern did not differ significantly by duration of US residence category in the Mexico-born Mexican-American population. However, in comparison to all Mexico-born Mexican Americans, US-born Mexican Americans had significantly lower score for the Tomato/Tortilla pattern, and significantly higher score for the Western pattern. Scores for the Healthy pattern were relatively low in all Mexican-American subgroups, indicating low adherence to the Healthy diet. However, Healthy diet scores of Mexico-born Mexican Americans among those aged ≤41 years appeared more similar to those of US-born non-Hispanic whites than US-born Mexican Americans. Education and policy action promoting healthy food access in Hispanic neighborhoods could help limit consumption of Western and Coffee/Sugar diet patterns and promote healthier choices in the Mexican-American population.


[Postoperative modifications of blood aminoacidemic concentration].
Post-operative plasmatic aminoacid concentrations in 2 groups of patients given surgical treatment for various pathologies have been calculated. In both groups, post-traumatic protein catabolism was expressed in significant changes to the aminoacidemic pattern. It is concluded that aminoacidograms could be used as a guide to rational parenteral post-operative treatment.


Group B streptococcus (GBS) is an important pathogen in human disease- but what about in cystic fibrosis?
Group B Streptococcus (GBS) is a common commensal capable of causing severe invasive infections. Most GBS infections occur in neonates (often as pneumonia). GBS can also cause infection in adults with diabetes and other immunological impairments but rarely leads to pneumonia in adults. GBS has occasionally been found in the sputum of Cystic Fibrosis (CF) patients, an inherited condition known for progressive lung disease. However, the epidemiology and clinical significance of GBS in CF are not understood. We retrospectively reviewed a large single-centre adult CF population with an associated comprehensive, prospectively collected bacterial biobank beginning in 1978. We identified all individuals with GBS isolated from their sputum on at least one occasion. The primary outcome was risk of pulmonary exacerbation (PEx) at the time of the first GBS isolate compared to the preceding visit. Secondary outcomes included determining: prevalence of GBS infection in a CF population, whether GBS infections where transient or persistent, whether GBS strains were shared among patients, change in % predicted FEV1 at the time of GBS isolate compared to the preceding visit, PEx frequency after the first GBS isolate, change in % predicted FEV1 after the first GBS isolate, and complications of GBS infection. GBS was uncommon, infecting 3.5% (11/318) adults within our cohort. Only three individuals developed persistent GBS infection, all lasting > 12 months. There were no shared GBS strains among patients. PEx risk was not increased at initial GBS isolation (RR 5.0, CI 0.69-36.1, p=0.10). In the two years preceding initial GBS isolation compared to the two following years, there was no difference in PEx frequency (median 2, range 0-4 vs 1, range 0 to 5, respectively, p=0.42) or lung function decline, as measured by % predicted FEV1, (median -1.0%, range -19 to 7% vs median -6.0%, range -18 to 22%, p=0.86). There were no invasive GBS infections. In adults with CF, GBS is uncommon and is generally a transient colonizer of the lower airways. Despite the presence of structural lung disease and impaired innate immunity in CF, incident GBS infection did not increase PEx risk, PEx frequency, rate of lung function decline, or other adverse clinical outcomes.


Automatic snoring detection using a hybrid 1D-2D convolutional neural network.
Snoring, as a prevalent symptom, seriously interferes with life quality of patients with sleep disordered breathing only (simple snorers), patients with obstructive sleep apnea (OSA) and their bed partners. Researches have shown that snoring could be used for screening and diagnosis of OSA. Therefore, accurate detection of snoring sounds from sleep respiratory audio at night has been one of the most important parts. Considered that the snoring is somewhat dangerously overlooked around the world, an automatic and high-precision snoring detection algorithm is required. In this work, we designed a non-contact data acquire equipment to record nocturnal sleep respiratory audio of subjects in their private bedrooms, and proposed a hybrid convolutional neural network (CNN) model for the automatic snore detection. This model consists of a one-dimensional (1D) CNN processing the original signal and a two-dimensional (2D) CNN representing images mapped by the visibility graph method. In our experiment, our algorithm achieves an average classification accuracy of 89.3%, an average sensitivity of 89.7%, an average specificity of 88.5%, and an average AUC of 0.947, which surpasses some state-of-the-art models trained on our data. In conclusion, our results indicate that the proposed method in this study could be effective and significance for massive screening of OSA patients in daily life. And our work provides an alternative framework for time series analysis.


Midodrine for the weaning of vasopressor infusions.
Midodrine, an orally available α1-agonist indicated for the treatment of orthostatic hypotension, has been used at our institution as an adjunctive treatment to provide haemodynamic support to facilitate intravenous (IV) vasopressor weaning. Limited published data exist for this off-label use; thus, the objective of this study was to evaluate outcomes in patients who received midodrine for IV vasopressor weaning compared to control patients. This retrospective comparison included adult ICU patients admitted to our institution from January 2007 to March 2012. The primary outcome was the time to IV vasopressor discontinuation after midodrine initiation. Secondary outcomes included a comparison between midodrine and control patients of the time from IV vasopressor discontinuation to ICU discharge, hospital and ICU length of stay (LOS), and the number of ICU readmissions. The analysis included 188 patients (94 midodrine and 94 control). Patients discontinued IV vasopressors a median of 1·2 days (IQR 0·5-2·8) after midodrine initiation. ICU discharge occurred sooner after IV vasopressor discontinuation (0·8 vs. 1·5 days, P = 0·01), and 96% of patients remained off IV vasopressors after midodrine treatment. Hospital LOS was longer in midodrine patients (P < 0·01), but there were no differences in ICU LOS or readmissions. Adverse event rates after midodrine use were consistent with those observed in other studies. Midodrine may serve as a useful adjunct to wean IV vasopressors in difficult-to-wean patients. Further studies are needed to assess the efficacy and safety of midodrine for this indication.


Illusory displacement of equiluminous kinetic edges.
A stationary window was cut out of a stationary random-dot pattern. When a field of dots was moved continuously behind the window (a) the window appeared to move in the same direction even though it was stationary, (b) the position of the 'kinetic edges' defining the window was also displaced along the direction of dot motion, and (c) the edges of the window tended to fade on steady fixation even though the dots were still clearly visible. The illusory displacement was enhanced considerably if the kinetic edge was equiluminous and if the 'window' region was seen as 'figure' rather than 'ground'. Since the extraction of kinetic edges probably involves the use of direction-selective cells, the illusion may provide insights into how the visual system uses the output of these cells to localize the kinetic edges.


Salutary effects of the prostacyclin analogue CG 4203 in lethal endotoxemia in rats.
In pentobarbitone anesthetized rats infusion of E. coli endotoxin (0.42 mg.kg-1.min-1 for 4 hours) produced 96% lethality within 6 hours. Transient decrease in mean arterial blood pressure, thrombocytopenia, leukopenia, loss of plasma fibrinogen, fibrin deposits in renal glomeruli, hemolysis and decrease in arterial oxygen tension and pH were observed. Infusion of the prostacyclin analogue CG 4203 (0.464 and 1.0 micrograms.kg-1.min-1 for 6 hours), starting concomitantly with the endotoxin infusion, improved the survival rate to 95 and 100%. Blood pressure during endotoxemia was slightly lower in CG 4203 treated rats than in vehicle controls. CG 4203 infusion marginally attenuated thrombocytopenia and obviously inhibited leukopenia, but did not effect fibrinogen consumption in endotoxemic rats. Incidence of glomerular fibrin deposits was dose dependently and significantly reduced by CG 4203. The lower dose reduced and the higher dose completely prevented the occurrence of hemolysis. Acidotic changes were not observed in CG 4203 treated endotoxin-shocked rats. Also with treatment starting 1 hour after the onset of endotoxemia CG 4203 in the same doses significantly inhibited the endotoxin-induced lethality. As protective mechanisms against lethal rat endotoxemia the prostacyclin-like hemodynamic, fibrinolytic, rheological and membrane stabilizing properties of CG 4203 are discussed.


Transcriptome analyses reveals the dynamic nature of oil accumulation during seed development of Plukenetia volubilis L.
Sacha inchi (Plukenetia volubilis L.) is a shrub native to Amazon rainforests that's of commercial interest as its seeds contain 35-60% edible oil (dry weight). This oil is one of the healthiest vegetable oils due to its high polyunsaturated fatty acid content and favourable ratio of omega-6 to omega-3 fatty acids. De novo transcriptome assembly and comparative analyses were performed on sacha inchi seeds from five stages of seed development in order to identifying genes associated with oil accumulation and fatty acid production. Of 30,189 unigenes that could be annotated in public databases, 20,446 were differentially expressed unigenes. A total of 14 KEGG pathways related to lipid metabolism were found, and 86 unigenes encoding enzymes involved in α-linolenic acid (ALA) biosynthesis were obtained including five unigenes encoding FATA (Unigene0008403), SAD (Unigene0012943), DHLAT (Unigene0014324), α-CT (Unigene0022151) and KAS II (Unigene0024371) that were significantly up-regulated in the final stage of seed development. A total of 66 unigenes encoding key enzymes involved in the synthesis of triacylglycerols (TAGs) were found, along with seven unigenes encoding PDCT (Unigene0000909), LPCAT (Unigene0007846), Oleosin3 (Unigene0010027), PDAT1 (Unigene0016056), GPDH (Unigene0022660), FAD2 (Unigene0037808) and FAD3 (Unigene0044238); these also proved to be up-regulated in the final stage of seed development.


Psychological distress, fatigue and long-term sickness absence: prospective results from the Maastricht Cohort Study.
Little is known about psychological distress as a risk factor for the onset of long-term sickness absence and even less about the influence of fatigue in this relationship. We examined the relationship between psychological distress and the onset of long-term sickness absence during 18 months of follow-up while considering fatigue. Analyses were based on 6403 employees participating in the Maastricht Cohort Study. Psychological distress was related to the onset of long-term sickness absence (women relative risk 1.45, 95% confidence interval = 1.23-1.72; men 1.33, 1.21-1.46). Adjustment for fatigue weakened the associations, particularly in women. Caseness analyses revealed different effects of psychological distress and fatigue in the onset of long-term sickness absence in men and women. The findings underline the need for interventions aiming at psychological distress and, depending on the gender, also at fatigue, to reduce the risk of long-term sickness absence.


Strong impact of estrogen environment on Doppler variables used for differentiation between benign and malignant breast lesions.
To analyze the impact of an estrogen environment on the Doppler variables usually used for differentiation between benign and malignant lesions. A total of 142 malignant and 107 benign breast lesions was demonstrated (in 91 premenopausal and 152 postmenopausal patients) by B-mode ultrasound. Intratumoral vessels were visualized by color Doppler and blood flow velocity waveforms were analyzed by pulsed Doppler. The number of intratumoral vessels and the Doppler variables, peak systolic velocity, resistance and pulsatility indices and the peak systolic/diastolic ratio were evaluated in different endocrine milieus represented by menopausal status, phase of the menstrual cycle, intake of oral contraceptives or hormone replacement therapy. In malignant tumors the Doppler variables resistance and pulsatility indices and the systolic/diastolic ratio were significantly higher in postmenopausal women than in premenopausal women. In benign tumors significantly higher values of resistance and pulsatility indices were also detected in post- compared to premenopausal women (P < or = 0.05). In premenopausal patients with benign tumors taking oral contraceptives the number of intratumoral vessels was significantly higher, while resistance index and systolic/diastolic ratio values were decreased compared to patients with spontaneous menstrual cycles. In postmenopausal patients hormone replacement therapy did not influence Doppler variables in the benign or the malignant groups. Our results demonstrate a robust influence of menopausal status and oral contraceptives on Doppler variables of breast lesions. We believe it is likely that some of the differences in the Doppler variables found in reports comparing benign and malignant breast lesions were caused by their association with a pre- or postmenopausal status.


Correlation of abdominal CT imaging with autopsy findings in patients with malignant tumors.
The value of abdominal computed tomography (CT) in diagnosing localized involvement of liver, pancreas, adrenals, and lymph nodes was evaluated in 117 patients with suspected or known malignant tumors by correlation with autopsy findings. Sensitivity, specificity, and accuracy of CT for localized liver disease was calculated to be 80% (84%), 96% (97%), and 90% (92%); for pancreatic tumors: 81% (86%), 98% (100%), and 95% (97%); for adrenal tumors: 65% (92%), 100% (100%), and 92% (98%); and for lymph node enlargement 75 (88%), 97% (98%), and 87% (94%), respectively. Results of routine evaluation could be improved, especially in the adrenal region, when scans were reevaluated by highly experienced examiners (results given in parenthesis). Computed tomography is a highly valuable diagnostic tool in the primary diagnosis and in the follow-up of tumor patients. The high costs are offset by a reduction in invasive procedures and a shortened hospital stay.


Pan-cancer atlas of somatic core and linker histone mutations.
Recent genomic data points to a growing role for somatic mutations altering core histone and linker histone-encoding genes in cancer. However, the prevalence and the clinical and biological implications of histone gene mutations in malignant tumors remain incompletely defined. To address these knowledge gaps, we analyzed somatic mutations in 88 linker and core histone genes across 12,743 tumors from pediatric, adolescent and young adult (AYA), and adult cancer patients. We established a pan-cancer histone mutation atlas contextualized by patient age, survival outcome, and tumor location. Overall, 11% of tumors harbored somatic histone mutations, with the highest rates observed among chondrosarcoma (67%), pediatric high-grade glioma (pHGG, >60%), and lymphoma (>30%). Previously unreported histone mutations were discovered in pHGG and other pediatric brain tumors, extending the spectrum of histone gene alterations associated with these cancers. Histone mutation status predicted patient survival outcome in tumor entities including adrenocortical carcinoma. Recurrent pan-cancer histone mutation hotspots were defined and shown to converge on evolutionarily conserved and functional residues. Moreover, we studied histone gene mutations in 1700 pan-cancer cell lines to validate the prevalence and spectrum of histone mutations seen in primary tumors and derived histone-associated drug response profiles, revealing candidate drugs targeting histone mutant cancer cells. This study presents the first-of-its-kind atlas of both core and linker histone mutations across pediatric, AYA, and adult cancers, providing a framework by which specific cancers may be redefined in the context of histone and chromatin alterations.


Quantitative analysis of gliding between subcutaneous tissue and the vastus lateralis - Influence of the dense connective tissue of the myofascia.
The thickness of connective tissue has been shown to be associated with pain (Stecco et al., 2014). However, the relationship between fascial thickness and gliding remains unclear. In addition, the influence between gliding and the motion rhythm and limb position isn't clear. A therapist moved patient's lower leg at one of two constant rhythms (40 or 60bpm). Gliding of both the vastus lateralis (VL) muscle and subcutaneous (SC) tissue were recorded during knee motion using ultrasonography. Particle image velocimetry analysis software was adapted to create the flow velocity from echo imaging. Gliding was calculated using a coefficient of correlation from each flow velocity. Myofascial thickness and SC were measured using Image-J. The ratios of the loose connective tissue (LCT) and dense connective tissue (DCT) thickness to the total myofascial thickness were calculated. Repeated-measures two-way ANOVA was used to compare the two motion rhythms and three positions, with stepwise multiple regression analysis to analyze the predictors that influenced the gliding coefficient at each rhythm. Repeated-measures two-way ANOVA showed that the effect of rhythm was statistically significant, but the effect of position was not. At a 40 bpm rhythm, stepwise multiple regression analysis selected SC thickness and DCT thickness as significant factors, while at a 60 bpm rhythm, SC thickness and DCT ratio were selected. This study revealed that increased thickness of DCT of the myofascia and SC resulted in decreased gliding between the VL and SC, demonstrating that gliding is related to fascial thickness. Motion rhythm influences gliding between tissues.


Poly(anhydride-ester) gemcitabine: Synthesis and particle engineering of a high payload hydrolysable polymeric drug for cancer therapy.
Gemcitabine (GMT) is a nucleoside analog used in the treatment of a variety of solid tumors. GMT was chemically modified with a hydrolysable linker, and subsequently incorporated into a poly(anhydride-ester) backbone via melt-polymerization, with the active antimetabolite GMT, thus, becoming the repeat unit that makes up this new material, a biodegradable polymer. Characterization of the structure of polymeric GMT (polyGMT) revealed the incorporation of an average 26 molecules of GMT per polymer chain, which corresponds to a drug loading of 58%w/w. The glass transition temperature of the formed polyGMT was determined to be 123 °C. PolyGMT was engineered into nanoparticles (NPs) using a dialysis-based method, with a resulting geometric diameter of 206 ± 38 nm. The particles are easily dispersible and stable in aqueous-based media, with a hydrodynamic diameter of 229 ± 28 nm. The prepared hydrolysable polyGMT NPs demonstrate ultra-long release profile due to the hydrophobic nature of the linker, and as per characteristic erosion behavior of polymers with anhydride-ester bonds. Accelerated in vitro release studies demonstrate the recovery of free GMT upon hydrolysis, with biological activity as assessed by cytotoxicity assays performed in adenocarcinoma human alveolar basal epithelial (A549) and highly metastatic murine osteosarcoma (K7M2) cells lines. The characteristics of polyGMT, including its thermal properties and built in hydrolysable structure, are thus conducive for use in the preparation of drug delivery systems. Engineered structures prepared with polyGMT can maintain their morphology at ambient and physiologically relevant conditions, and free GMT is recovered as the anhydride and ester bonds are hydrolyzed. This work is innovative as for the first time we demonstrate the ability to polymerize GMT in a hydrolysable polymer structure, and engineer NPs of this polymeric chemotherapy. The synthetic strategy allows for tuning of the polymer hydrophobicity and thus potentialize its behavior, including degradation profile, by varying the linker chemistry. Such controlled release hydrolysable polymers with very high drug loading and controlled erosion profiles are relevant as they may offer new opportunities in drug delivery applications for the treatment of malignant neoplasms.


Toxic effects of nicotinamide methylation on mouse brain striatum neuronal cells and its relation to manganese.
It is well known that manganese (Mn) exposure is involved in parkinsonism. The aim of our study was to test the hypotheses that Mn affects nicotinamide N-methyltransferase (NNMT) activity, increases the metabolism of nicotinamide (NA) to 1-methylnicotinamide (MNA), and leads to neurocytotoxicity. Following demonstration of the effects of Mn concentrations on the survival rate of Mouse CD1 brain striatum neuronal cells (MS cells), the effect of Mn on NNMT activity was investigated by comparing the difference in the amount of MNA produced after various Mn concentrations were added to mouse brain cytosol fractions as an enzyme solution. Toxicity induced by MNA and its precursor NA on MS cells was measured. The survival rate of MS cells decreased significantly with increasing concentrations of Mn in the culture medium. With respect to the influence of Mn on NNMT activity, NNMT activity increased significantly at Mn concentrations of 1 μmol/mg protein. MNA and NA neurotoxicity were compared by comparing cell survival rate. Cell survival rate dropped significantly when the cells were cultivated with 10 mM of MNA. There was also a tendency for the survival rate to fall following the addition of 10 mM NA; however, the difference with the control was not significant. Our study suggests the possibility that Mn causes increased NNMT activity, thereby increasing MNA levels in the brain and bringing about neuron death. Daily absorption of Mn and NA may thus contribute to idiopathic Parkinson's disease.


Antibiograms of pathogenic bacteria isolated from laboratory animals.
Study of antibiotic sensitivity patterns of 178 bacterial isolants from laboratory animals revealed that these bacteria in general were sensitive to many commonly used antibiotics; however, there were notable exceptions. This report presents current antibiotic sensitivity patterns of most gram-negative and gram-positive bacterial pathogens common to laboratory animals.