Difference in expression between AQP1 and AQP5 in porcine endometrium and myometrium in response to steroid hormones, oxytocin, arachidonic acid, forskolin and cAMP during the mid-luteal phase of the estrous cycle and luteolysis.
Recently, we demonstrated in vitro that AQP1 and AQP5 in the porcine uterus are regulated by steroid hormones (P4, E2), arachidonic acid (AA), forskolin (FSK) and cAMP during the estrous cycle. However, the potential of the porcine separated uterine tissues, the endometrium and myometrium, to express these AQPs remains unknown. Thus, in this study, the responses of AQP1 and AQP5 to P4, E2 oxytocin (OT), AA, FSK and cAMP in the porcine endometrium and myometrium were examined during the mid-luteal phase of the estrous cycle and luteolysis. Real-time PCR and western blot analysis. Progesterone up-regulated the expression of AQP1/AQP5 mRNAs and proteins in the endometrium and myometrium, especially during luteolysis. Similarly, E2 also stimulated the expression of both AQPs, but only in the endometrium. AA led to the upregulation of AQP1/AQP5 in the endometrium during luteolysis. In turn, OT increased the expression of AQP1/AQP5 mRNAs and proteins in the myometrium during mid-luteal phase. Moreover, a stimulatory effect of forskolin and cAMP on the expression of AQP1/AQP5 mRNAs and proteins in the endometrium and myometrium dominated during luteolysis, but during the mid-luteal phase their influence on the expression of these AQPs was differentiated depending on the type of tissue and the incubation duration. These results seem to indicate that uterine tissues; endometrium and myometrium, exhibit their own AQP expression profiles in response to examined factors. Moreover, the responses of AQP1/AQP5 at mRNA and protein levels to the studied factors in the endometrium and myometrium are more pronounced during luteolysis. This suggests that the above effects of the studied factors are connected with morphological and physiological changes taking place in the pig uterus during the estrous cycle.


An HRP study of hypothalamo-cerebellar and cerebello-hypothalamic connections in squirrel monkey (Saimiri sciureus).
This study describes the distribution of labeled hypothalamic neurons in squirrel monkey following pressure injections of horseradish peroxidase (HRP) into cerebellar cortex and the pattern of labeling in the cerebellar nuclei subsequent to iontophoretic injections localized in the hypothalamus. Two types of HRP (HRP and a wheat germ agglutinin conjugate, HRP-WGA) were used as tracers; tetramethylbenzidine was the chromogen. Retrogradely filled neurons were found in lateral (LHAr) and posterior (PHAr) hypothalamic areas, and in the lateral mammillary (LMNu) and supramammillary (SMNu) nuclei following injections into ansiform and paramedian lobules and into the paraflocculus. Labeled cells were occasionally seen in the medial mammillary nucleus (parafloccular cases) and among fascicles of the mammillothalamic tract (all posterior lobe cases) immediately above the medial nucleus. After injections into the anterior lobe, labelling was again found in the LHAr, PHAr, LMNu, and SMNu. In addition, retrogradely filled cells were present in ventromedial, dorsomedial, and dorsal hypothalamic nuclei and in the dorsal hypothalamic area. Labeled cells were occasionally found among fascicles of the fornix along its intrahypothalamic course. In general, labeling extends into slightly more rostral hypothalamic levels in anterior lobe cases when compared to posterior lobe experiments. We interpret these data as indicating that some hypothalamic neurons project directly to the cerebellar cortex (i.e., hypothalamo-cerebellar fibers); this projection is bilateral with an ipsilateral preponderance. In experiments with injections of HRP-WGA into the cerebellar nuclei, anterogradely filled axons were traced into the contralateral PHAr and LHAr; this was suggestive of a direct cerebello-hypothalamic projection. Following iontophoretic injections localized in the LHAr and the medial mammillary nucleus, labeling was seen in the medial (NM), posterior interposed (NIP), and lateral (NL) cerebellar nuclei; this is essentially a contralateral projection. Retrogradely labeled cells were found in the rostral and ventral NM, the ventral and dorsocaudal NL, and diffusely throughout the NIP. On the basis of the known distribution of cerebello-thalamic fibers and other criteria, these labeled cells are representative of a true cerebello-hypothalamic projection. It is suggested that the cerebellum, through these pathways, may have a relatively direct influence on visceral centers in the brainstem and spinal cord.


Hypercoagulation in COPD: the clot thickens.
There is a growing body of evidence that hypercoagulability is present in stable COPD, involves changes in multiple coagulation factors, and is not simply associated with major causes of inflammation and thrombosis https://bit.ly/3F5NnfN.


Expression of immediate early gene proteins following axotomy and inhibition of axonal transport in the rat central nervous system.
The expression of the immediate early gene-encoded proteins c-Jun, Jun B, Jun D, c-Fos, Fos B and Krox-24 in central neurons following transection of, or inhibition of, axonal transport in their axons was investigated in the rat using immunocytochemistry. Transection of the medial forebrain bundle, which produces an essentially complete axotomy of neurons in the ipsilateral mammillary nucleus, substantia nigra pars compacta, ventral tegmental area and parafascicularis, induced the expression of c-Jun, Jun D and, to a lesser extent, Krox-24, in these nuclei. Microinjection of colchicine into the medial forebrain bundle to chemically inhibit axonal transport similarly induced the expression of these proteins in these areas. The expression of the proteins was first evident 24 h after transection, reached a maximum at 48 h and was still present after 10 days. However, after 30 days the proteins were absent from the substantia nigra, ventral tegmentum and parafascicularis, and were still present only in the mammillary nuclei. The other immediate early genes, Jun B, c-Fos and Fos B, were never expressed above the basal levels seen in untreated rats. Transection of the corpus callosum and the hippocampal commissure, which produces only a partial axotomy of neurons in the cerebral cortex and hippocampus, respectively, did not induce the expression of any of the genes in these neurons. Microinjection of colchicine or vinblastine to produce a localized inhibition of axonal transport in the cerebral cortex, hippocampus, thalamus and cerebellum also induced the expression of c-Jun, Jun D and, again to a lesser extent, Krox-24, in neurons surrounding the injection site. In contrast to this selective expression, administration of the neuronal excitant metrazole induced the expression of all six immediate early gene proteins in central nervous system neurons. These results demonstrate that transection of, or inhibition of, transport in the axons of central neurons induces a particular pattern of expression of transcriptionally operating immediate early genes that may be related to the regenerative competency of the neurons.


Proteomic approach reveals that starch degradation contributes to anthocyanin accumulation in tuberous root of purple sweet potato.
A comparative proteomic approach was carried out to investigate anthocyanin biosynthesis in the tuberous roots of yellow sweet potato (YSP) and purple sweet potato (PSP) cultivars. More than 800 proteins were reproducibly detected through two-dimensional electrophoresis (2-DE), of which 50 proteins with 39 more and 11 less accumulated in PSP were identified through matrix-assisted laser desorption ionization-time of flight/time of flight mass spectrometry (MALDI-TOF/TOF-MS). Most of the analyzed proteins are annotated to be involved in starch metabolism and glycolysis. The more abundant starch phosphorylase (SP) and phosphoglucomutase (PGM) in PSP promoted the synthesis of precursors for anthocyanin synthesis. The results implied that starch degradation provided abundant substrates for anthocyanin biosynthesis in tuberous roots of PSP. 24kDa vacuolar protein (VP24) is related to anthocyanin transport and accumulation in vacuoles. Vacuole-associated annexin protein, VCaB42, is correlated with tonoplast biogenesis. Synergistic action of the two proteins is probably involved in the microautophagy and the intravacuolar trapping of anthocyanins. Interestingly, both VCaB42 and VP24 were more accumulated in PSP, suggesting that anthocyanins generated in the cytosol were transported into and became stored in the vacuoles of PSP. The present study provides new insights into the mechanism of tuberous root-specific anthocyanin accumulation in PSP. Sweet potato ranks as the seventh most important crop worldwide. Purple sweet potato, a special sweet potato cultivar, has been extensively investigated because large amounts of anthocyanin accumulate in its tuberous roots. Anthocyanin is well known for its free radical-scavenging activity and beneficial effects on human health. Its biosynthetic pathway has been well characterized in model plants. Although large-scale systematic studies have been performed to identify the proteins present in sweet potato, information on the regulation of anthocyanin synthesis in sweet potato is insufficient. Our proteome study demonstrated that starch degradation may contribute to anthocyanin accumulation in purple sweet potato. To our knowledge, this study is the first to propose that starch degradation may provide precursors of anthocyanin biosynthesis in sweet potato.


Lipid droplet-specific near-infrared fluorescent probe for discriminating cancer and normal cells and diagnosing fatty liver.
Lipid droplets (LDs) is a newly essential organelle, which participates in carious physiological and pathological processes. LDs are considered as potential markers for disease diagnosis. Specific imaging of LDs is useful to understand their basic biological function and to diagnose diseases. Here we designed and synthesized two fluorescent probes based on the low polarity and high viscosity in LDs. The terminal probe ZH-2 exhibits lipophilicity, NIR emission, viscosity sensitivity, and LDs specificity. The probe has been successfully used for visualizing LDs metabolism, discriminating between normal and cancerous cells, and diagnosing fatty liver disease.


Comparison of background in underground HPGe-detectors in different lead shield configurations.
In underground HPGe-detector systems where the cosmic ray induced background is low, it is often difficult to assess the location of background sources. In this study, background counting rates of different HPGe-detectors in different lead shields are reported with the aim of better understanding background sources. To further enhance the understanding of the variations of environmental parameters, the background as a function of time over a long period was also studied.


Treatment of diabetes mellitus using an external insulin pump: the state of the art.
The aim of diabetes treatment is to achieve tight glucose control to avoid the development of chronic diabetic complications while reducing the frequency of hypoglycaemic episodes. Continuous subcutaneous insulin infusion (CSII) using an external pump is an intensive diabetes therapy recognized to improve metabolic control and glycaemic instability, and to reduce the frequency of severe hypoglycaemia. For years, the theoretical advantages of the insulin pump (constancy of basal delivery, adjustable basal rates, and low insulin depots allowing the reduction of glycaemic variability) have contributed to its reported superiority compared with multiple daily injections (MDI). However, insulin pump therapy is now challenged by new MDI regimens based on long-acting insulin analogues that could replace the use of CSII. As a consequence, health professionals now have to determine which patients are likely to benefit the most from CSII. Recently, several studies reported that children and adolescents, and patients whose blood glucose imbalance was initially the most pronounced with basal-bolus regimens, would particularly benefit from CSII. Other indications were also proposed in marginal clinical situations with highly selected patients in whom a significant improvement of blood glucose was demonstrated. Finally, the use of CSII in type 2 diabetic patients now appears to be a good alternative to the ineffective MDI regimens observed in some of these patients. However, past experience with CSII indicates that candidates for insulin pump therapy must be carefully selected and strongly motivated to improve their glucose control. Use of CSII also requires strict medical supervision by physicians and a regular programme of patient education by paramedical teams, to ensure optimal responsible use of this technique by healthcare professionals.


[Systemic treatment of penile cancer: New concepts? New achievements?]
Systemic chemotherapy has been in use for metastatic penile carcinoma for years, but its success is limited. Its significance is largely associated with its role in multimodal treatment for lymphatic metastasis in the context of radical lymph node surgery. In cases of limited lymph node involvement, the combination of surgical treatment plus cisplatin- and taxane-based triple combinations may be curative. Advances in the understanding of molecular changes in penile cancer and the search for potential therapy targets have led to numerous studies. Although there is evidence of efficacy of immunotherapeutics, no significant therapeutic improvements have been seen in the clinical routine.


Bilateral rostral maxillectomy and nasal planectomy for large rostral maxillofacial neoplasms in six dogs and one cat.
This paper describes in detail an aggressive rostral maxillectomy procedure in one cat and six dogs, and the postoperative complications and outcomes are reported. The surgeries were performed to attempt complete excision of large and extensive rostral maxillary fibrosarcomas (n=4), squamous cell carcinomas (n=2), or poorly differentiated mesenchymal neoplasia (n=1). The surgeries involved transection of the maxilla at the level of premolar (PM)1 and PM2 in a cat and two dogs, and between PM2 and PM3 in four dogs. There were no intraoperative complications. Complete margins of resection were obtained in all cases. The postoperative appearance was acceptable to owners. Local recurrence was only observed in one dog (10 months after surgery) during a follow-up period of 11 to 66 months (median, 21.5 months).


Chandelier Cells Illuminate Inhibitory Control of Prefrontal-Amygdala Outputs.
Inhibitory interneurons comprise a diverse subpopulation of cells that are critical to circuit function. How distinct inhibitory microcircuits control long-range projections remains poorly understood. A recent study by Lu and colleagues uncovered a unidirectional microcircuit of prefrontal chandelier cells that preferentially innervate and suppress long-range amygdala-projecting pyramidal cells.


Chronic ACL-injured patients show increased medial and global anterior tibial subluxation measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction.
The association between chronic anterior cruciate ligament (ACL) injury and inferior postoperative outcomes following ACL reconstruction (ACLR) has been highlighted in the literature. However, the inclusion of postoperative radiological assessments in previous studies has been limited. The aim of this study is to investigate whether chronic ACL injury is associated with an inferior tibiofemoral position measured on magnetic resonance (MR) images after primary ACLR. A total of 62 patients that underwent primary ACLR were included in this study based on the time from injury to surgery, namely the acute ACL-injured group (within 6 weeks) and the chronic ACL-injured group (more than 1 year) and were matched 1:1 according to sex, age (± 2 years), and time from surgery to follow-up (± 3 months). Patient demographics, surgical records and follow-up data were retrieved and analyzed. The altered tibiofemoral position was measured quantitatively on preoperative and at least 1-year postoperative MR images and compared between the two groups, including the lateral, medial and global anterior tibial subluxation (LATS, MATS and GATS) and internal rotational tibial subluxation (IRTS). No significant differences in preoperative LATS, MATS, GATS or IRTS were identified between the acute and chronic ACL-injured groups. The chronic ACL-injured patients showed significantly increased postoperative MATS (p = 0.001) and GATS (p = 0.012), while no significant difference was identified in postoperative LATS or IRTS. Multivariate linear regression analyses showed that chronic ACL injury resulted in an estimated increase of 2.0 mm in postoperative MATS (p = 0.012) and 1.9 mm in postoperative GATS (p = 0.040). A significant improvement in postoperative LATS was observed in the acute ACL-injured group (p = 0.044) compared to preoperative LATS, while no improvements in these MRI measurements were observed in the chronic ACL-injured group. Chronic ACL-injured patients showed increased MATS and GATS measured on 1-year postoperative MR images after primary single-bundle ACL reconstruction, while no difference was identified in rotational tibiofemoral position. The acute ACL-injured group demonstrated a significant improvement in postoperative LATS, whereas no improvements were observed in the chronic ACL-injured group. Level of evidence Level III.


Do laboratories follow heart failure recommendations and guidelines and did we improve? The CARdiac MArker Guideline Uptake in Europe (CARMAGUE).
Natriuretic peptides (NP) are well-established markers of heart failure (HF). During the past 5 years, analytical and clinical recommendations for measurement of these biomarkers have been published in guidelines. The aim of this follow-up survey was to investigate how well these guidelines for measurement of NP have been implemented in laboratory practice in Europe. Member societies of the European Federation of Clinical Chemistry and Laboratory Medicine were invited in 2009 to participate in a web-based audit questionnaire. The questionnaire requested information on type of tests performed, decision limits for HF, turn-around time and frequency of testing. There was a moderate increase (12%) of laboratories measuring NP compared to the initial survey in 2006. The most frequently used HF decision limits for B-type NP (BNP) and N-terminal BNP (NT-proBNP) were, respectively, 100 ng/L and 125 ng/L, derived from the package inserts in 55%. Fifty laboratories used a second decision limit. Age or gender dependent decision limits were applied in 10% (8.5% in 2006). The vast majority of laboratories (80%) did not have any criteria regarding frequency of testing, compared to 33% in 2006. The implementation of NP measurement for HF management was a slow process between 2006 and 2009 at a time when guidelines had just been established. The decision limits were derived from package insert information and literature. There was great uncertainty concerning frequency of testing which may reflect the debate about the biological variability which was not published for most of the assays in 2009.


Correspondence in Stakeholder Assessment of Health, Work Capacity and Sick Leave in Workers with Comorbid Subjective Health Complaints? A Video Vignette Study.
Purpose The purpose of this study is to test if there is correspondence in stakeholders' assessments of health, work capacity and sickness certification in four workers with comorbid subjective health complaints based on video vignettes. Methods A cross sectional survey among stakeholders (N = 514) in Norway in 2009/2010. Logistic regression and multinomial logistic regression was used to obtain the estimated probability of stakeholders choosing 100 % sick leave, partial sick leave or work and the estimation of odds ratio of stakeholder assessment compared to the other stakeholders for the individual worker. Results The supervisors were less likely to assess poor health and reduced work capacity, and more likely to suggest partial sick leave and full time work compared to the GPs for worker 1. The public was less likely to assess comorbidity and reduced work capacity, and 6 and 12 times more likely to suggest partial sick leave and full time work compared to the GPs for worker 1. Stakeholders generally agreed in their assessments of workers 2 and 3. The public was more likely to assess poor health, comorbidity and reduced work capacity, and the supervisors more likely to assess comorbidity and reduced work capacity, compared to the GPs for worker 4. Compared to the GPs, all other stakeholders were less likely to suggest full time work for this worker. Conclusions Our results seem to suggest that stakeholders have divergent assessments of complaints, health, work capacity, and sickness certification in workers with comorbid subjective health complaints.


Comparison of the Effectiveness of Various Drug Interventions to Prevent Etomidate-Induced Myoclonus: A Bayesian Network Meta-Analysis.
Myoclonic movement is a very common but undesirable phenomenon during the induction of general anesthesia using etomidate. Such movement may cause unnecessary problems. Currently, there is an increasing number of drugs for preventing etomidate-induced myoclonus (EM). However, direct comparisons of various drugs are lacking, and this interferes with clinical decision-making. Our network meta-analysis (NMA) aimed to compare the efficacy of different drugs for the prevention of moderate-to-severe general myoclonus. Using several biomedical databases, randomized controlled trials (RCTs) published in English from inception to August 22, 2021 were searched. Among the various interventions, we selected nine types of intervention drugs (dexmedetomidine, etomidate, lidocaine, NMDA receptor antagonist, κ opioid receptor agonist, μ opioid receptor agonist, muscle relaxant, gabapentin, and midazolam) for comparison, according to the number of studies. Bayesian NMA was performed using STATA16 and R softwares. The relative risk of EM was assessed using risk ratios (RRs) and the corresponding 95% confidence intervals (CI). A total of 31 RCTs (3209 patients) were included. NMA results showed that, compared with a placebo, etomidate (RR 4.0, 95%CI 2.1-7.8), κ opioid receptor agonist (RR 2.9, 95%CI 1.9-4.6), μ opioid receptor agonist (RR 3.1, 95%CI 2.3-4.3), NMDA receptor antagonist (RR 1.7, 95%CI 1.0-2.8), dexmedetomidine (RR 2.4, 95%CI 1.5-3.9), lidocaine (RR 2.1, 95%CI 1.2-3.9), and midazolam (RR 2.2, 95%CI 1.5-3.2) can significantly reduce the risk of EM. In contrast, the effects of muscle relaxants (RR 2.1, 95%CI 0.81-5.3) and gabapentin (RR 2.8, 95%CI 0.92-9.3) were inconclusive. Further subgroup analyses showed that preoperative low-dose etomidate, μ-opioid receptor agonist, and κ-opioid receptor agonist were significantly better than other interventions in the prevention of moderate to severe EM. Preoperative use of small doses of etomidate or opioids may be the most effective way to avoid EM, especially moderate and severe EM, which makes anesthesia induction safer, more stable, and aligns better with the requirements of comfortable medicine. [https://www.crd.york.ac.uk/prospero/], [CRD4202127706].


Prolactinemia is uncoupled from central D2/D3 dopamine receptor occupancy in amisulpride treated patients.
Atypical antipsychotic drugs are classically associated with lower propensity to extrapyramidal symptoms (EPS) and hyperprolactinemia than typical antipsychotic drugs. It has not been clarified why some atypical antipsychotic drugs, such as amisulpride, induce prolactin plasma concentration (PRL) elevation, but little EPS. Previous studies have found an association between striatal D2/D3 receptor occupancy and PRL in typical antipsychotic treated patients suggesting that PRL is a marker of central D2/D3 receptors blockade. We have evaluated the relationship between PRL and central (striatum, temporal cortex and thalamus) D2/D3 receptor occupancy in amisulpride treated schizophrenic patients. Single photon emission tomography (SPET) and [123I]-epidepride were used to determine D2/D3 receptor occupancy in eight amisulpride treated patients. PRL was measured concurrently with the scans. The mean PRL was 1166 (range 499-1892 mIU/l) for a mean amisulpride dose of 406 mg/day (range 150-600 mg/day). Amisulpride plasma concentration and central D2/D3 receptor occupancy were positively correlated (r=0.83-0.89, df=4, P<0.05). No significant correlations were observed between PRL and amisulpride (daily dose or plasma concentration, P>0.05), or between PRL and central D2/D3 receptor occupancy (P>0.05). Our findings show that amisulpride-induced hyperprolactinemia is uncoupled from central D2/D3 receptor occupancy. Amisulpride has poor blood-brain barrier penetration and reaches much higher concentration at the pituitary, which is outside the blood-brain barrier. Higher D2/D3 receptor occupancy at the pituitary gland than at central regions is a possible explanation for amisulpride PRL elevation with low EPS. Further studies evaluating pituitary D2/D3 receptor occupancy in vivo are necessary to confirm this hypothesis.


Chandelier cells in the hippocampal formation of the rat: the entorhinal area and subicular complex.
In the present study we describe the characteristics of the chandelier cells in the rat entorhinal cortex and subicular complex by using the Golgi method and combined Golgi-electron microscopic techniques. In the entorhinal cortex, chandelier cells were frequently stained in layers II/III. Two types of axonal complexes were noted. One had a preferential horizontal orientation and gave rise to terminals located in the upper portion of layers II/III. The second type of chandelier cell axon was observed in the medial entorhinal area, innervating the entire extent of layers II/III. In the subicular complex, chandelier cells were frequently stained in the parasubiculum, whereas only a few cells were found in the presubiculum. In both subfields, chandelier cell axons were restricted to layers II/III. In the subiculum, most chandelier cells were present in the stratum radiatum, giving rise to a descending axon that branched in the stratum pyramidale. Both the size and morphological features of the chandelier cell terminal portions were found to be region-specific. Electron microscopically, the cell body and dendrites of gold-toned chandelier cells displayed typical features of nonpyramidal cells, such as the presence of nuclear infoldings, symmetric and asymmetric synapses on the cell body, and moderate numbers of axon terminals covering the smooth dendritic surface. Five gold-toned chandelier cell axonal complexes were analyzed at the fine structural level. In all parahippocampal regions, gold-labeled axon terminals formed symmetric synaptic contacts with axon initial segments. Our results demonstrate the presence, morphological characteristics, and target selectivity of identified chandelier cells in the parahippocampal region of the rat. Together with previous data, these results suggest a wide distribution of this specialized type of cortical interneuron and indicate that it is a constant and essential component of inhibitory circuits in the cerebral cortex. The possible significance of chandelier cells for the circuits linking several subfields of the hippocampal formation is discussed.


Further purification of human pituitary-derived chondrocyte growth factor: heparin-binding and cross-reactivity with antiserum to basic FGF.
The previously described human pituitary-derived chondrocyte growth factor (CGF), mitogenic for rabbit fetal chondrocytes, was found to bind to heparin-Sepharose and was eluted with 1.5M NaCl. Further characterization of CGF demonstrated a molecular weight of 18-20 kD and cross-reactivity with antiserum to synthetic bovine basic fibroblast growth factor (FGF1-24). When human pituitaries were homogenized in 0.15 ammonium sulfate (pH 5.5) and the extract chromatographed on heparin-Sepharose, 98% of the mitogenic activity was adsorbed to heparin and eluted with 3M NaCl. These findings indicate that CGF is closely related or identical to basic FGF and that the bulk of mitogenic activity in the human pituitary extracts binds to heparin.


Characterization of a highly purified membrane proteinase from bovine lens.
A highly purified bovine lens membrane proteinase has been obtained. The purification was accomplished by solubilization of the proteinase from the membrane with 2% sodium deoxycholate followed by gel-filtration chromatography. The purified proteinase showed a major protein band having molecular weight of 17,000 on sodium dodecyl sulfate-polyacrylamide-gel electrophoresis (SDS-PAGE) and an active band on a non-denaturing acrylamide gel. The proteinase existed as a tetramer having a molecular weight of 68,000 as determined by gel-filtration chromatography. The proteinase had a pH optimum of 7.8 and was unstable above 40 degrees C. It lacked any requirement for metal ions for activity and was inhibited by all serine proteinase inhibitors tested. The proteinase hydrolysed mostly arginine amide and ester bonds. Based on its properties, the newly isolated membrane proteinase seems to be distinct from any mammalian lens proteinase isolated so far.


Role of epigenetically regulated inflammation in renal diseases.
In recent decades, renal disease research has witnessed remarkable advances. Experimental evidence in this field has highlighted the role of inflammation in kidney disease. Epigenetic dynamics and immunometabolic reprogramming underlie the alterations in cellular responses to intrinsic and extrinsic stimuli; these factors determine cell identity and cell fate decisions and represent current research hotspots. This review focuses on recent findings and emerging concepts in epigenetics and inflammatory regulation and their effect on renal diseases. This review aims to summarize the role and mechanisms of different epigenetic modifications in renal inflammation and injury and provide new avenues for future research on inflammation-related renal disease and drug development.


Translational bioinformatics: linking the molecular world to the clinical world.
Translational bioinformatics represents the union of translational medicine and bioinformatics. Translational medicine moves basic biological discoveries from the research bench into the patient-care setting and uses clinical observations to inform basic biology. It focuses on patient care, including the creation of new diagnostics, prognostics, prevention strategies, and therapies based on biological discoveries. Bioinformatics involves algorithms to represent, store, and analyze basic biological data, including DNA sequence, RNA expression, and protein and small-molecule abundance within cells. Translational bioinformatics spans these two fields; it involves the development of algorithms to analyze basic molecular and cellular data with an explicit goal of affecting clinical care.


Influence of implant neck design on facial bone crest dimensions in the esthetic zone analyzed by cone beam CT: a comparative study with a 5-to-9-year follow-up.
To examine the influence of two different neck designs on facial bone crest dimensions in esthetic single implant sites after a 5-to-9-year follow-up analyzed by cone beam computed tomography (CBCT). Sixty-one patients with an implant-borne single crown following early implant placement in the esthetic zone were enrolled. The test group consisted of a bone level (BL) neck design exhibiting a hydrophilic micro-rough surface combined with a platform-switching interface (PS) (n = 20). The control group comprised a soft tissue level (STL) neck design exhibiting a hydrophobic machined surface with a matching butt-joint interface (n = 41). Standardized clinical, radiologic, and esthetic parameters were applied. The facial bone crest dimensions were assessed by CBCT. Soft tissue parameters and pink esthetic scores yielded no significant differences between the two designs. Major differences were only observed at the implant shoulder level. The height of the facial bone crest for the BL design was located 0.2 mm above the implant shoulder level, whereas for the STL design, its location was 1.6 mm below. The width of the peri-implant saucer-like bone defect was reduced by 40% for the BL implant design. No differences were observed 2 mm below the shoulder level. The results of this comparative study suggest better crestal bone stability on the facial aspect of single implant sites in the esthetic zone for a BL design with a platform-switching concept when compared with STL implants with a butt-joint interface.


Immunohistochemical localisation of keratin in small cell carcinoma of the lung: correlation with response to combination chemotherapy.
Immunohistochemical localisation of keratin was assessed on 45 diagnostic specimens of small cell carcinoma of the lung in patients who subsequently received combination chemotherapy. Nine out of 45 (20%) contained keratin immunoreactive cells. Six of these achieved a complete response to treatment compared to 12 of the tumours which did not show positive staining for keratin. For 2 patients the tumours were shown to contain nests of keratin immunoreactive cells. Both of these are alive and free of disease more than 5 yr after the initial diagnosis. The results indicate that the presence of keratin immunoreactive cells may not directly equate with squamous differentiation and therefore not constitute an adverse prognostic factor in terms of response to chemotherapy.


[Fragments of a correspondence between the Parisian pharmacist Émile Vial and the Dutch painter Johan-Barthold Jongkind].
We study a series of exchanged original letters between the Parisian pharmacist art lover Émile Vial (1833-1917) and the Dutch painter Johan-Barthold Jongkind (1819 - 1891) from april 13th, 1876 till February 1th, 1887.


A mouse model of endocardial fibroelastosis.
Endocardial fibroelastosis (EFE) is a pathologic condition of abnormal deposition of collagen and elastin within the endocardium of the heart. It is seen in conjunction with a variety of diseases including hypoplastic left heart syndrome and viral endocarditis. While an experimental model using heterotopic heart transplant in rats has been described, we sought to fully describe a mouse model that can be used to further elucidate the potential mechanisms of and treatments for EFE. The hearts of 2-day-old C57BL/6 mice were transplanted into the abdomen of 7-week-old C57BL/6 mice. At 2 weeks, the hearts were harvested and histologic analysis was performed using hematoxylin and eosin, Masson's trichrome, Russell-Movat's pentachrome, Picrosirius red, Hart's, Verhoeff-Van Gieson, and Weigert's Resorcin-Fuchsin stains. Additionally, one heart was analyzed using transmission electron microscopy (TEM). Specimens demonstrated abnormal accumulation of both collagen and elastin within the endocardium with occasional expansion into the myocardium. Heterogeneity in extracellular matrix deposition was noted in the histologic specimens. In addition, TEM demonstrated the presence of excess collagen within the endocardium. The heterotopic transplantation of an immature heart into a mouse results in changes consistent with EFE. This model is appropriate to investigate the etiology and treatment of EFE.


Identification of eight copper (Cu) uptake related genes from yellow catfish Pelteobagrus fulvidraco, and their tissue expression and transcriptional responses to dietborne Cu exposure.
The present working hypothesis is that absorption of dietary Cu is related to mRNA expressions of genes involved in Cu uptake and transport of the intestine in fish. To this end, the full-length cDNA sequences of eight Cu uptake related genes, including two isoforms of copper transporter genes (ctr1 and ctr2), three copper chaperone genes (atox1, ccs and cox17), two Cu-ATPase genes (atp7a and atp7b) and divalent metal ion transporter 1 (dmt1), were cloned and characterized in yellow catfish P. fulvidraco, respectively. Their mRNA tissue expression and transcriptional responses to dietborne Cu exposure were investigated. Compared to the corresponding members of mammals, all of these members in P. fulvidraco shared the similar conserved domain structures. Their mRNAs were expressed in a wide range of tissues (including liver, muscle, spleen, brain, gill, intestine, heart and kidney), but at variable levels. In anterior intestine, mRNA levels of ctr1, cox17, dmt1 and atp7a declined with increasing dietary Cu levels. The mRNA levels of ctr2 and mt were the highest for excess dietary Cu group and showed no significant differences between other two treatments. Atox1 mRNA levels were the highest for Cu-deficient group and showed no significant differences between other two treatments. The mRNA levels of ccs were the highest for Cu-deficient group, followed by Cu-excess group and the lowest for adequate-Cu group. In contrast, atp7b mRNA levels were the highest for Cu-excess group and the lowest for adequate Cu group. In the mid-intestine, mRNA levels of ctr1, ctr2, atox1, ccs, cox17, dmt1 and atp7a declined with increasing dietary Cu levels. Atp7b mRNA levels were the lowest for adequate Cu group and showed no significant differences between other two treatments. Mt mRNA levels were the lowest for adequate Cu group and highest for Cu-excess group. For the first time, our study cloned and characterized ctr1, ctr2, atox1, ccs, cox17, atp7a, atp7b and dmt1 genes in P. fulvidraco and determined their tissue-specific expression, and transcriptional responses in the anterior and mid-intestine of yellow catfish under dietborne Cu exposure, which shed new light on the Cu uptake system and help to understand the molecular mechanisms of Cu homeostasis in fish.


Oral administration of Euglena gracilis Z and its carbohydrate storage substance provides survival protection against influenza virus infection in mice.
Euglena gracilis Z is a micro-algae that is used as a food or nutritional supplement. Paramylon, the carbohydrate storage substance of Euglena gracilis Z has β-1, 3-glucan structure. Euglena gracilis Z and paramylon are reported to affect the immune system. In this study, we investigated the protective effects of Euglena gracilis Z and paramylon against influenza virus infection in mice. Euglena gracilis Z and paramylon were administered to mice as a 2% dietary mixture ad libitum. At 2 weeks after initiation of dietary administration, mice were infected intranasally with influenza virus A/PR/8/34 (H1N1). Survival rate was monitored 10 days after infection. In addition, we performed virus titer and cytokine profiles in the lung. High survival rates were observed for Euglena gracilis Z and paramylon-treated groups compared to the control group. Significantly lower virus titer in the lung was observed in the Euglena gracilis Z and paramylon-treated groups compared to the control group from day 1 after infection. Higher amount of IL-1β, IL-6, IL-12 (p70), IFN-γ, and IL-10 was observed in the paramylon groups compared to the control group. Our data therefore reveals a novel immunoregulatory role of the Euglena gracilis Z and paramylon which provides protection against influenza virus infection.


Cervical conization before primary radical hysterectomy has a protective effect on disease recurrence in early cervical cancer: A two-center matched cohort study according to surgical approach.
To ascertain whether cervical conization before radical hysterectomy (RH) has a protective effect on survival outcomes in early cervical cancer, taking into account the surgical approach. From cervical cancer cohorts of two institutions, we identified node-negative, margin-negative, parametria-negative, 2009 FIGO stage IB1 cervical cancer patients who received primary Type C RH between July 2006 and June 2020. Patients were divided into conization group (n = 144) and control group (n = 434). We conducted three independent 1:1 propensity score matching processes for histology, lymphovascular space invasion, cervical tumor size, and surgical approach (all patients, those who underwent open surgery, and those who underwent minimally invasive surgery [MIS]). Survival outcomes were compared. Overall, the conization group had less cervical tumor size and received MIS more frequently (P = 0.010) and adjuvant treatment less often (P = 0.002) versus the controls. After matching, the conization group showed significantly better disease-free survival (DFS) versus control (3-year DFS rate, 94.2% vs. 86.3%; P = 0.012), but similar overall survival. Among the open RH matched patients (n = 96), no difference in DFS was observed between the conization and control groups (P = 0.984). In contrast, among the MIS RH matched patients (n = 192), the conization group showed significantly better DFS versus control (3-year DFS rate, 95.7% vs. 82.9%; P = 0.005). In multivariate analysis adjusting for cervical tumor size and adjuvant treatment, conization was identified as an independent favorable prognostic factor for DFS (adjusted HR, 0.318; 95% CI, 0.134-0.754; P = 0.009). Preoperative cervical conization might reduce the disease recurrence rate in early cervical cancer patients who undergo primary MIS RH.


Progress in research on natural cellulosic fibre modifications by polyelectrolytes.
In order to improve the mechanical properties and functionalities of natural cellulosic fibres, this paper first analyzed the characteristics of natural cellulosic fibres and the conventional modification methods of natural cellulosic fibres, and then focused on the polyelectrolytes modified natural cellulosic fibres. The main methods and process parameters of this modification were described in detail; the modification effects of polyelectrolytes on different types of fibres were systematically summarized; the influencing factors on modification of fibres were also discussed in depth; the characterization methods of polyelectrolytes modified fibres were analyzed in detail. Finally, the main application fields of polyelectrolytes modified fibres were systematically summarized.


Nonsurgical management of neonatal multiple brain abscesses due to Proteus mirabilis.
A newborn infant with Proteus mirabilis meningitis developed multiple brain abscesses with diameters ranging from 2 to 4 cm. Intravenous antibiotic therapy alone without surgical intervention led to the complete resolution of this complication. The case supports that this may be an acceptable treatment of multiple brain abscesses in neonates. However, the clinical outcome was relatively poor, since a porencephalic cyst, hypodense areas in CT scan, and psychomotor retardation were found at one year of age.


Continuous venovenous renal replacement therapy in critically ill patients: A work load analysis.
To evaluate the nursing workload related to two techniques of continuous renal replacement therapy. We analysed retrospectively the nursing work load caused directly by continuous renal replacement therapy in a cohort of patients admitted consecutively over 10 months. Two types of continuous renal replacement therapy have been compared: dialysis with regional citrate anticoagulation and haemodiafiltration with systemic heparin coagulation. Academic Hospital Intensive Care Unit. The nursing workload was defined by the time spent in the management of continuous renal replacement therapy, including preparation of the circuit and related biological controls. 60 patients underwent a total of 202 sessions of continuous renal replacement therapy. The nursing workload as expressed as % time of nursing care was similar (12.3 [9.4-18.8] vs 13.4 [11.7-17.0] %, for haemodiafiltration and dialysis respectively, P=0.06). However, the distribution of the nursing workload is different: the bigger proportion of care is circuit preparation in haemodiafiltration and biology control in dialysis. Nursing time dedicated to continuous renal replacement therapy is similar whatever the renal replacement therapy technique. However, a longer duration of the filter and a better circuit predictability with dialysis and citrate anticoagulation are potential benefits for nursing workload.


Application of Bayesian Space-Time interaction models for Deer-Vehicle crash hotspot identification.
The objective of this research was to identify and prioritize deer-vehicle crash (DVC) hotspots using five years of crash data. This study applied Bayesian spatiotemporal models for the identification of the DVC hotspots. The Bayesian spatiotemporal model allows to observe area-specific trends in the DVC data and highlights specific locations where DVC occurrence is deteriorating or improving over time. Census Tracts (CTs) were used as the geographic units to aggregate DVC, land use, and transportation infrastructure related data of Minnesota (MN) for the year 2015 to 2019. Several tests were conducted to evaluate the performance of the hotspot identification methods. The result showed that Type-I spatiotemporal interaction model (Model-2) outperforms other four space-time models in terms of predicting DVC frequency in CTs and hotspot identification performance test measures. Results showed that forest area, vegetation, and wetland percentages were positively associated with DVC frequency, whereas the percentage of developed land use was negatively associated with DVC frequency. The findings of this study suggest that the deer population plays an important role in DVCs, which indicates that deer population management is necessary to minimize the DVC risks. Using the final Type-I spatiotemporal interaction model, 65 "High-High" CTs were identified, where both the posterior mean of the decision parameter (potential for safety improvement) and the area-specific trend were higher. The distribution of the identified hotspots showed that the risk of DVCs was more in suburban areas with mixed land use conditions. These CTs represent high-risk zones, which need immediate safety improvement measures to reduce the DVC risks. As DVC can occur at any roadway segment location, DVC hotspots information is important for safety engineers and policymakers to implement area specific countermeasures.


Genetic risk and gynecologic cancers.
Although most gynecologic malignancies are sporadic, hereditary cancer syndromes cause a substantial portion of these cancers. Given that the diagnosis of these syndromes has prognostic and therapeutic implications for the patient, as well as preventive implications for her family members, genetic testing is now an accepted part of the management of the patient who has gynecologic cancer.


Reduction of elevated plasma globotriaosylsphingosine in patients with classic Fabry disease following enzyme replacement therapy.
Fabry disease is treated by two-weekly infusions with α-galactosidase A, which is deficient in this X-linked globotriaosylceramide (Gb3) storage disorder. Elevated plasma globotriaosylsphingosine (lysoGb3) is a hallmark of classical Fabry disease. We investigated effects of enzyme replacement therapy (ERT) on plasma levels of lysoGb3 and Gb3 in patients with classical Fabry disease treated with agalsidase alfa at 0.2mg/kg, agalsidase beta at 0.2mg/kg or at 1.0mg/kg bodyweight. Each treatment regimen led to prominent reductions of plasma lysoGb3 in Fabry males within 3 months (P=0.0313), followed by relative stability later on. Many males developed antibodies against α-galactosidase A, particularly those treated with agalsidase beta. Patients with antibodies tended towards smaller correction in plasma lysoGb3 concentration, whereas treatment with high dose agalsidase beta allowed a reduction comparable to patients without antibodies. Pre-treatment plasma lysoGb3 concentrations of Fabry females were relatively low. In all females and with each treatment regimen, ERT gave reduction or stabilisation of plasma lysoGb3. Our investigation revealed that ERT of Fabry patients reduces plasma lysoGb3, regardless of the recombinant enzyme used. This finding shows that ERT can correct a characteristic biochemical abnormality in Fabry patients.


Increased Occurrence of Tracheal Intubation-Associated Events During Nights and Weekends in the PICU.
Adverse tracheal intubation-associated events are common in PICUs. Prior studies suggest provider and practice factors are important contributors to tracheal intubation-associated events. Little is known about how the incidence of tracheal intubation-associated events is affected by the time of day, day of the week, or presence of in-hospital attending-level intensivists. We hypothesize that tracheal intubations occurring during nights and weekends are associated with a higher frequency of tracheal intubation-associated events. Retrospective observational cohort study. Twenty international PICUs. Critically ill children requiring tracheal intubation. None. We analyzed 5,096 tracheal intubation courses from July 2010 to March 2014 from the prospective multicenter National Emergency Airway Registry for Children. Frequency of a priori-defined tracheal intubation-associated events was the primary outcome. Occurrence of any tracheal intubation-associated events and severe tracheal intubation-associated events were more common during nights (19:00 to 06:59) and weekends compared with weekdays (19% vs 16%, p = 0.01; 7% vs 6%, p = 0.05, respectively). This difference was significant in emergent intubations after adjusting for site-level clustering and patient factors: for any tracheal intubation-associated events: adjusted odds ratio, 1.20; 95% CI, 1.02-1.41; p = 0.03; but not significant in nonemergent intubations: adjusted odds ratio, 0.94; 95% CI, 0.63-1.40; p = 0.75. For emergent intubations, PICUs with home-call attending coverage had a significantly higher frequency of tracheal intubation-associated events during nights and weekends (adjusted odds ratio, 1.29; 95% CI, 1.01-1.66; p = 0.04), and this difference was attenuated in PICUs with in-hospital attending coverage (adjusted odds ratio, 1.12; 95% CI, 0.91-1.39; p = 0.28). Higher occurrence of tracheal intubation-associated events was observed during nights and weekends. This difference was primarily attributed to emergent intubations. In- hospital attending physician coverage attenuated this discrepancy between weekdays versus nights and weekends but was not fully protective for tracheal intubation-associated events.


Revealing the trend and change point in Hargreaves equation based on potential evapotranspiration values with various statistical approaches.
Hotter and drier weather conditions due to climate change negatively affect water resources and agricultural production. For this reason, it is vital to analyze the change in potential evapotranspiration (PET) values, which is one of the most important parameters related to plant growth and agricultural irrigation planning. This study analyses the trends and changes in monthly and annual PET values between 1965 and 2018 at Erzincan, Bayburt and Gümüşhane meteorological stations in Turkey. For this purpose, monotonic trends in PET values were determined by Spearman's rho (SR), Mann-Kendall (MK), Şen slope (SS), and innovative trend analysis (ITA) tests and change points were analyzed with the sequential MK (SQMK) test. The Hargreaves equation was used to calculate the PET values. As a result of the study, according to MK and SR tests, while increasing trends at 95% and 99% significance levels were dominant at Erzincan and Bayburt stations, no statistically significant trends were found at Gümüşhane station except in February. ITA generally detected more than 5% increasing trends in PET data's low, medium, and high values. According to ITA slope analysis, there are significant increase trends in PET values at all periods, trend 1% significance level. According to the SQMK test, it was revealed that the trend started in PET values, especially in 1995, 2005, and 2010. The findings emphasized the importance of taking measures against decreased agricultural production and managing water resources effectively.


Alterations of the cortical evoked potential by topical application of taurine.
The effects of topical application of taurine and glycine upon cortical evoked potentials induced by tactile stimulation have been studied in urethane-anaesthetized rats. The amplitudes of both the primary positive component (P1) and the following negative wave (N1) of the evoked potential were markedly increased by the application of 25 mM taurine but were not significantly altered by 25 mM glycine. These results indicate a possible depressant action of taurine at superficial cortical layers.


Theory of mind, language and the temporoparietal junction mystery.
Brain imaging of adults during false-belief story tasks consistently shows activation of the temporoparietal junction in English-speaking Americans and German-speaking Europeans. Kobayashi et al. find this observation in adult English speakers but not in English-speaking children or in English-Japanese bilingual persons. This finding suggests a cultural or linguistic influence on location of brain function and argues against maturation of innately specified neural substrates. It is reminiscent of effects of linguistic development, bilingualism and cultural differences on theory of mind development.


Anaerobic and microaerophilic pathogens in the biofilm formation on voice prostheses: A pilot study.
Voice rehabilitation with voice prostheses is a standard therapy in laryngectomized patients. Biofilm formation on the surface of the voice prostheses causes device failure and requires frequent replacements. Studies analyzing the biofilm of voice prostheses have mainly focused on aerobic bacteria. Anaerobic bacteria as an integral part of the biofilms on voice prostheses have not been investigated yet. Prospective pilot study on the occurrence of anaerobic and microaerophilic pathogens in biofilm formation on voice prostheses. Biofilm samples of 15 voice prostheses were analyzed using a polymerase chain reaction-based hybridization method regarding the presence of 11 selected anaerobic and microaerophilic pathogens. In 80% of the voice prostheses, at least one and up to 10 of the tested bacteria could be identified. Fusobacterium nucleatum was the pathogen most often present (73%). Other frequently occurring pathogens were Treponema denticola (40%), Tannerella forsythia (33%), and Eikenella corrodens (33%). There was no correlation between the number of identified bacteria and the indwelling times (mean, 127 days; maximum, 344 days; minimum, 22 days). For the first time, anaerobic and microaerophilic pathogens have been identified as part of the biofilm formation on the surface of voice prostheses. Those pathogens might be responsible for accelerated biofilm formation and reduced lifetime of the voice prostheses.


Over-expression of hTERT in CHO K1 results in decreased apoptosis and reduced serum dependency.
The enzyme telomerase plays a crucial role in cellular proliferation. By adding hexameric repeats to the chromosome ends, it prevents telomeric loss and, thus entry into senescence of limited life span cells. It is unclear, however, what would be the effect of over-expressing telomerase in an immortalised cell line, characterised by unlimited life span and high levels of apoptosis under sub-optimal growth conditions. In order to address this question, we have transfected the immortal cell line CHO K1 with the human telomerase reverse transcriptase (hTERT) catalytic subunit. Differences in the growth profile and apoptosis levels between the cells over-expressing hTERT (Telo) and the cells containing mock vector were found under standard growth conditions. Similarly, the Telo cells showed lower levels of apoptosis, greater attachment tendency and higher viable cell density under serum-deprived conditions compared to the control cell line, suggesting a major role for hTERT over-expression in stressed cultures. Using a mouse cDNA microarray, the collagen type III and V genes were shown to have at least a 10-fold higher expression in the Telo cells than the control cells, suggesting a role of hTERT in the cell attachment pathways.


Cascade strand displacement reaction-assisted aptamer-based highly sensitive detection of ochratoxin A.
Ochratoxin A (OTA) is a toxic metabolite that is widely distributed in food products. Herein, we proposed a new fluorescent aptasensor for OTA detection by using cascade strand displacement reaction. The binding of OTA and OTA aptamer on magnetic beads surface inhibited its hybridization with complementary DNA, and subsequently initiated the strand displacement reaction that induced amplified fluorescence signal. By tracing fluorescence response, our method demonstrated an improved detection limit of 0.63 ng/mL, a short assay time of 110 min, and a satisfactory detection specificity by using ochratoxin B, aflatoxin B1, and zearalenone as control toxins. Recovery studies were conducted by spiking OTA in real food samples, including white wine, red wine, cereal drink, coffee beverage and tea beverage, and confirmed desirable accuracy and practical applicability of our method. Therefore, our method may have a great potential use in the food quality control in the future.


Directly Observed Weekly Fluoxetine for Major Depressive Disorder Among Hemodialysis Patients: A Single-Arm Feasibility Trial.
Major depressive disorder (MDD) is common among hemodialysis patients, but treatment can add to their pill burden and may be limited by nonadherence. We sought to investigate the value of directly observed, once-weekly fluoxetine dosing in MDD. Feasibility trial of adult hemodialysis patients with untreated MDD. The diagnosis of MDD was determined using the Mini International Neuropsychiatric Interview. 16 patients at 15 hemodialysis facilities in Northeast Ohio. Patients were initially prescribed 20 mg of fluoxetine once daily for 2 weeks to assess their tolerance. The patients took this daily fluoxetine unobserved at home. They were then transitioned to 90 mg of fluoxetine once weekly for 10 weeks. The patients took this weekly fluoxetine during hemodialysis treatment and were observed by the study staff. The dose was increased to 180 mg once weekly among patients with an inadequate response based on the judgment of the prescribing clinician. Mini International Neuropsychiatric Interview diagnosis of MDD at the end of the trial and changes in the Patient Health Questionnaire (PHQ-9) scores over 12 weeks. One patient withdrew from active treatment after 2 daily doses of 20 mg of fluoxetine because of side effects of stomach cramping, vomiting, dizziness, and lightheadedness but completed the baseline and final assessments. The remaining 15 patients received all scheduled weekly fluoxetine doses during the trial. At 12 weeks, 14 of 16 patients (87.5%) no longer met the criteria for MDD (P < 0.001). Among all participants, the mean PHQ-9 scores decreased from 11.3 to 6.6 (P = 0.002). Small sample size, modestly elevated baseline PHQ-9 scores, no comparison group, and short treatment duration. Directly observed, once-weekly fluoxetine may be an effective and well-tolerated treatment option for hemodialysis patients. Future research should investigate longer-term health outcomes of weekly fluoxetine in this population and explore the feasibility of implementing this depression treatment model in routine clinical practice. This trial was registered at clinicaltrials.gov as NCT03390933.


The effect of alpha and gamma interferon on cell growth and histocompatibility antigen expression by human renal carcinoma cells in vitro.
Tumour cells were separated from 19 renal carcinomas and cultured in vitro. The effect of interferon (IFN) alpha and gamma on cell proliferation was measured and compared to the effect of IFN on the expression of class I and class II major histocompatibility complex (MHC) antigens. When tested within the first 14 days of culture, IFN-alpha inhibited protein synthesis in 12 of 15 and IFN-gamma in four of nine tumours. Reduction in cell counts was in parallel. In six tumours the culture period was extended and in all six the effect of IFN-alpha was lost. Exposure to IFN-alpha induced or enhanced class I antigen expression in eight of 19 tumours and class II expression in two of 19. The analogous figures for IFN-gamma were five and three tumours. In four of five cases where a comparison could be made there was a correlation between the effects of IFN-alpha on cell proliferation and class I antigen expression. The efficacy of IFN in the treatment of renal carcinomas may thus, in part, result from inhibition of cell proliferation and enhancement of antigen expression.


Feasibility, limitation and possible solutions of RNAi-based technology for insect pest control.
Numerous studies indicate that target gene silencing by RNA interference (RNAi) could lead to insect death. This phenomenon has been considered as a potential strategy for insect pest control, and it is termed RNAi-mediated crop protection. However, there are many limitations using RNAi-based technology for pest control, with the effectiveness target gene selection and reliable double-strand RNA (dsRNA) delivery being two of the major challenges. With respect to target gene selection, at present, the use of homologous genes and genome-scale high-throughput screening are the main strategies adopted by researchers. Once the target gene is identified, dsRNA can be delivered by micro-injection or by feeding as a dietary component. However, micro-injection, which is the most common method, can only be used in laboratory experiments. Expression of dsRNAs directed against insect genes in transgenic plants and spraying dsRNA reagents have been shown to induce RNAi effects on target insects. Hence, RNAi-mediated crop protection has been considered as a potential new-generation technology for pest control, or as a complementary method of existing pest control strategies; however, further development to improve the efficacy of protection and range of species affected is necessary. In this review, we have summarized current research on RNAi-based technology for pest insect management. Current progress has proven that RNAi technology has the potential to be a tool for designing a new generation of insect control measures. To accelerate its practical application in crop protection, further study on dsRNA uptake mechanisms based on the knowledge of insect physiology and biochemistry is needed.


Physiology and gene expression profiles of Dekkera bruxellensis in response to carbon and nitrogen availability.
The assimilation of nitrate, a nitrogenous compound, was previously described as an important factor favoring Dekkera bruxellensis in the competition with Saccharomyces cerevisiae for the industrial sugarcane substrate. In this substrate, nitrogen sources are limited and diverse, and a recent report showed that amino acids enable D. bruxellensis to grow anaerobically. Thus, understanding the regulation of nitrogen metabolism is one fundamental aspect to comprehend the competiveness of D. bruxellensis in the fermentation environment. In the present study, we evaluated the physiological and transcriptional profiles of D. bruxellensis in response to different carbon and nitrogen supplies to determine their influence on growth, sugar consumption, and ethanol production. Besides, the expression of genes coding for nitrogen permeases and enzymes involved in the biosynthesis of glutamate and energetic metabolism were investigated under these conditions. Our data revealed that genes related to nitrogen uptake in D. bruxellensis are under the control of nitrogen catabolite repression. Moreover, we provide indications that glutamate dehydrogenase and glutamate synthase may switch roles as the major pathway for glutamate biosynthesis in D. bruxellensis. Finally, our data showed that in nonoptimal growth conditions, D. bruxellensis leans toward the respiratory metabolism. The results presented herein show that D. bruxellensis and S. cerevisiae share similar regulation of GDH–GOGAT pathway, while D. bruxellensis converts less glucose to ethanol than S. cerevisiae do when nitrogen is limited. The consequence of this particularity to the industrial process is discussed.


Centrifugal regulation of neuronal activity in the olfactory bulb of the waking rabbit as revealed by reversible cryogenic blockade.
The influences of centrifugal projections to the olfactory bulb were examined on the bulbar EEG and mitral-tufted cell activity in waking rabbits. Each of 6 rabbits was implanted, under surgical anesthesia, with fine wire electrodes for recording of the EEG and mitral-tufted cell unit activity and for stimulating the lateral olfactory tract. Two cooling probes, for reversible cryogenic blockade, were implanted on either side of the left olfactory peduncle. Records of EEG and unit activity were taken for 200 s before, during and after cooling of the probes to 3 degrees centigrade. Antidromic evoked potentials were used to assess the efficacy of the blockade. During the cryogenic blockade bursts of EEG activity, evoked in the bulb by inspiration through the nose, were augmented in amplitude and reduced in frequency. Mitral-tufted cell unit activity was reduced in rate but was more highly correlated with the phase and amplitude of the EEG bursts. Analysis of individual EEG bursts revealed that the variance in frequency of bulbar activity was significantly reduced in the isolated state. The data demonstrate that oscillatory bursting activity in the olfactory bulb is intrinsically maintained within a relatively fixed frequency range during receptor input and does not depend on centrifugal projections for its electrogenesis. Changes in EEG frequency, amplitude and correlation with unit activity support the hypothesis that centrifugal projections act in part to inhibit mitral-tufted cell output by direct excitation of granule cells. These findings are supported by a theoretical model in which distributed feedback to the granule cells from more central olfactory structures acts to regulate the coherency of bulbar activity.


Physical activity screening to recruit inactive randomized controlled trial participants: how much is too much?
Screening physical activity levels is common in trials to increase physical activity in inactive populations. Commonly applied single-item screening tools might not always be effective in identifying those who are inactive. We applied the more extensive Active Australia Survey to identify inactive people among those who had initially been misclassified as too active using a single-item measure. Those enrolled after the Active Australia Survey screening had significantly higher physical activity levels at subsequent baseline assessment. Thus, more extensive screening measures might result in the inclusion of participants who would otherwise be excluded, possibly introducing unwanted bias. Australian New Zealand Clinical Trials Registry, ACTRN12611000157976.


Protein-energy interactions in the management of severe malnutrition.
The three syndromes of childhood malnutrition are contrasted with respect to protein. It is concluded that stunting and wasting are the outcomes of protein deficiency, and that kwashiorkor is not due to protein deficiency, rather it is related to unopposed oxidant stress. Formula for the energy and protein requirements are derived and contour plots of the amounts needed to sustain high rates of weight gain at different body compositions generated. It is suggested that all nutrients be expressed with energy as the denominator. No more than 12.5% of protein energy is required to sustain maximum likely rates of weight gain. Using this approach to design a diet, high rates of weight gain are achieved under field conditions in refugee camps.


Regulatory Implications of Non-Trivial Splicing: Isoform 3 of Rab1A Shows Enhanced Basal Activity and Is Not Controlled by Accessory Proteins.
Alternative splicing often affects structured and highly conserved regions of proteins, generating so called non-trivial splicing variants of unknown structure and cellular function. The human small G-protein Rab1A is involved in the regulation of the vesicle transfer from the ER to Golgi. A conserved non-trivial splice variant lacks nearly 40% of the sequence of the native Rab1A, including most of the regulatory interaction sites. We show that this variant of Rab1A represents a stable and folded protein, which is still able to bind nucleotides and co-localizes with membranes. Nevertheless, it should be mentioned that compared to other wild-typeRabGTPases, the measured nucleotide binding affinities are dramatically reduced in the variant studied. Furthermore, the Rab1A variant forms hetero-dimers with wild-type Rab1A and its presence in the cell enhances the efficiency of alkaline phosphatase secretion. However, this variant shows no specificity for GXP nucleotides, a constantly enhanced GTP hydrolysis activity and is no longer controlled by GEF or GAP proteins, indicating a new regulatory mechanism for the Rab1A cycle via alternative non-trivial splicing.


Outcomes among patients treated for gastric adenocarcinoma during the last decade.
To evaluate the outcomes among patients treated for gastric adenocarcinoma in a referral hospital, and to identify possible trends during the last decade. All patients evaluated for gastric adenocarcinoma during the period 1999-2009 were included. Of 397 patients, 52% were curatively resected. Crude 5-year survival for the first 6 years period was 38.7% (CI 29.5-47.9), for the last 5 years, 49.2% (CI 38.8-59.6). Time period (P = 0.013), age (P < 0.001) and disease stage (P < 0.001), were significant predictors of long-term survival rates. Among curatively resected, in-hospital mortality was reduced from 8.5% in the first period to 2.0% in the last one (P = 0.037). There was a significant increase in the use of primary stents from the first to the last period (P = 0.006), paralleled by a significant reduction in the number of explorative laparotomies or bypass procedures (P < 0.001). During the last decade, long-term survival rates improved among patients curatively resected for gastric adenocarcinoma, and in-hospital mortality was substantially reduced. For patients in a non-curative situation, there was a significant shift from explorative laparotomies or bypass procedures to primary use of stents.


Kanglaite enhances the efficacy of cisplatin in suppression of hepatocellular carcinoma via inhibiting CKLF1 mediated NF-κB pathway and regulating transporter mediated drug efflux.
Kanglaite (KLT) is an active extract of the Coix lacryma-jobi seed, which can benefit Qi and nourish Yin, and disperse the accumulation of evils. It is used as a biphasic broad-spectrum anti-cancer drug, and shows synergistic effects with radiotherapy and chemotherapy. However, the mechanism of KLT combined with cisplatin (CDDP) against hepatocellular carcinoma (HCC) has not been elucidated. The aim of present study was to investigate the potential synergistic effects of KLT and CDDP on HepG2 cells, discussing the possible mechanisms from the perspective of CKLF1 and NF-κB mediated inflammatory response and chemoresistance, and the involvement of drug efflux transporters. CDDP injured HepG2 cells were used to investigate the effects of KLT on chemotherapeutics treated HCC. Effects of KLT pretreatment on CDDP injured HepG2 cells were determined by MTT, wound healing assay, and transwell assay. Expression of chemokine-like factor 1 (CKLF1) and activation of nuclear factor κB (NF-κB) were examined by qPCR, western blot, and immunofluorescence staining. Furthermore, to study the role of CKLF1 in KLT mediated effects on this CDDP injured HCC cell model, HepG2 cells overexpressed with CKLF1 gene were used. Cell viability and NF-κB activation were investigated. Moreover, TNF-α and IL-1β levels were measured by Elisa analysis and western blot to evaluate the inflammatory response. Additionally, ATP-binding cassette (ABC) drug efflux transporters, MDR1, MRP2, and BCRP were also determined in present study. KLT pretreatment followed by CDDP treatment was found to show synergistic effects, which showed by decreased cell viability, migration and invasion ability of HepG2 cells. Expression of CKLF1 enhanced significantly in CDDP treated HepG2 cells, and KLT decreased this elevation obviously. Furthermore, CDDP activated NF-κΒ and promoted translocation of NF-κB toward the nucleus. KLT inhibited the activation of NF-κΒ, which sensitized cancer cells. Overexpression of CKLF1 reversed the effects of KLT on CDDP injured HepG2 cells, which exhibited by increased cell viability and enhanced activation of NF-κΒ. CDDP induced NF-κΒ activation could also lead to excessive inflammatory response, and KLT can suppress the aggravating inflammation which may be beneficial for tumor progression. Furthermore, we found that ABC drug efflux transporters MDR1, MRP2, and BCRP in CDDP treated HepG2 cells were decreased when pretreated with KLT. KLT pretreatment may increase the effects of CDDP on HepG2 cells, by exhibiting cooperative effects on suppression of HepG2 cells. The mechanisms may partly by inhibiting CKLF1 mediated NF-κB pathway, which may contribute to inflammation of tumor microenvironment and chemoresistance of CDDP. Inhibition of transporter-mediated drug efflux is also involved in KLT mediated sensitization effects of CDDP.


Effect of heat treatment on CO2 adsorption of KOH-activated graphite nanofibers.
In this work, graphite nanofibers (GNFs) were successfully expanded intercalating KOH followed by heat treatment in the temperature range of 700-1000 °C. The aim was to improve the CO(2) adsorption capacity of the GNFs by increasing the porosity of GNFs. The effects of heat treatment on the pore structures of GNFs were investigated by N(2) full isotherms, XRD, SEM, and TEM. The CO(2) adsorption capacity was measured by CO(2) isothermal adsorption at 25 °C and 1 atm. From the results, it was found that the activation temperature had a major influence on CO(2) adsorption capacity and textural properties of GNFs. The specific surface area, total pore volume, and mesopore volume of the GNFs increased after heat treatment. The CO(2) adsorption isotherms showed that G-900 exhibited the best CO(2) adsorption capacity with 59.2 mg/g.


Characterization of biochars derived from agriculture wastes and their adsorptive removal of atrazine from aqueous solution: A comparative study.
The physicochemical properties of biochars produced from soybeans (SBB), corn stalks (CSB), rice stalks (RSB), poultry manure (PMB), cattle manure (CMB), and pig manure (PgMB) and their adsorption characteristics of atrazine were investigated. The adsorption capacity increased with the increase of temperature and initial atrazine concentration. More atrazine was removed from basic solutions than acidic solutions, due to the effects of adsorption and hydrolysis. The Freundlich isotherm adsorption parameters indicated that the adsorption capacity decreased in the order SBB>RSB>CMB>CSB>PMB>PgMB, which is associated to the pore volume of biochars. The total pore volume and biochar pH were concluded to play important roles in determining the adsorption capacity, and they may have contributed to physical adsorption mechanisms dominating the overall adsorption process (the low activation energy for all of the biochars). Modified Freundlich and intraparticle diffusion models were used to describe the kinetics of the adsorption process.


Ethyl 1-(2-hy-droxy-eth-yl)-2-[2-(methyl-sulfan-yl)eth-yl]-1H-benzimidazole-5-carboxyl-ate.
In the crystal structure of the title compound, C(15)H(20)N(2)O(3)S, the hy-droxy group is involved in the formation of O-H⋯N hydrogen bonds, which link two mol-ecules into a centrosymmetric dimer. Weak C-H⋯O hydrogen bonds further link these dimers into chains propagating along the a axis. The crystal packing exhibits π-π inter-actions between the five- and six-membered rings of neighbouring mol-ecules [centroid-centroid distance = 3.819 (2) Å] and short inter-molecular S⋯S contacts of 3.495 (1) Å.


Studies of the role of the paramedian pontine reticular formation in the control of head-restrained and head-unrestrained gaze shifts.
Results of three experiments related to the role of the paramedian pontine reticular formation (PPRF) in the control of gaze are described. (1) Chronic unit recording methods, used to study the on-directions of short-lead burst neurons in head-restrained monkeys, and (2) reversible inactivation techniques confirmed the traditional view of the importance of PPRF in the control of horizontal eye movements. Reversible inactivation of neurons in the vicinity of identified short-lead burst neurons produced dramatic reductions in the speed of saccades to horizontal target displacements. The reductions in velocity were largely compensated for by an increase in saccade duration. Only minor, if any, effects were observed upon the velocity, duration, and amplitude of saccades to upward target displacements. (3) Microstimulation was applied to omnipause neurons to gate activity of excitatory burst neurons that discharge during coordinated eye-head movements. The microstimulation failed to noticeably slow (prevent) head movements when stimulation was applied during (prior to onset of) gaze shifts, suggesting that signals relayed to motoneurons innervating the neck muscles are not inhibited by the omnipause neurons. In other words, the desired gaze signal is parsed into eye and head pathways upstream of the excitatory burst neurons.


Acquired Coronary Artery Fistula With Pseudo-False Aneurysm Detected by Transthoracic Echocardiography After Myocardial Infarction.
Acquired coronary artery fistula complicated with a pseudo-false aneurysm after percutaneous coronary intervention for myocardial infarction is quite rare. In this clinical vignette, we describe the case of a 79-year-old man who was diagnosed by multimodality imaging, especially transthoracic echocardiography, and is doing well after left ventricle reconstruction. (Level of Difficulty: Intermediate.).


Immune recognition of insulin by H-2b mice: the mutation in the I-Ab beta gene of the B6.C-H-2bm12 mouse alters the self-I-A-restricted T cell repertoire.
The response to heterologous insulin in H-2b mice is restricted to the A chain loop determinant(s) of beef insulin. The recognition of this specificity requires the expression of the immune response (Ir) gene epitope Ia.W39 which is absent from the I-Ab mutant B6.C-H-2bm12 (bm12) mice. This restriction could reflect the inability of H-2b antigen-presenting cells (APC) to present other insulin determinants or may reflect "self-major histocompatibility complex"-dependent influences on the generation of the T cell repertoire. To assess these possibilities we analyzed the genetic control and fine specificity of the insulin-specific T cell repertoire of H-2b mice by fusing the AKR thymoma BW5147 with T cells of C57BL/6 mice which had been immunized in vivo and challenged in vitro with beef insulin. The cloned hybridomas that we have produced respond to APC either alone or in conjunction with insulin by the production of interleukin 2. The insulin-specific hybridomas vary in their fine specificity such that some clones recognize a determinant(s) shared by beef, sheep and pork insulin and the isolated B chain, while other clones recognize a determinant(s) shared by beef and sheep insulin only, likely to involve amino acids 8 and/or 10 of the A chain loop. The presentation of insulin to these hybridomas is restricted by I-Ab, but not by Ia.W39. This analysis revealed that the insulin-specific immune potential in H-2b mice is of greater scope than previously defined and led us to consider, whether insulin nonresponder bm12 mice also possess a latent insulin-specific immune potential. Our study of the insulin-specific immune recognition by bm12 mice shows that these nonresponders do possess insulin-specific T cell clones. Despite the fact that the I-Ab and I-Abm12 gene products differ only by 3 amino acids, insulin-specific C57BL/6 and bm12 hybridomas are restricted to recognize exogenous antigen only in the context of C57BL/6 and bm12 APC, respectively. Furthermore, upon direct analysis of autoreactive subclones, a similar although not complete, restriction was observed. The implications of these findings for understanding the mechanism of Ir gene control are discussed.


β-mannanase supplemented in diets saved 85 to 100 kcal of metabolizable energy/kg, supporting growth performance and improving nutrient digestibility in grower pigs.
The effects of β-mannanase supplementation in metabolizable energy (ME)-reduced diets containing xylanase-phytase were investigated on growth performance, fecal score, ultra-sounded backfat thickness and loin depth, blood profile, apparent total tract digestibility (ATTD), digesta passage rate, and fecal microbiome in grower pigs (n = 40, 26.09 ± 0.96 kg) randomly assigned within 4 treatments: a control diet containing isolated phytase and xylanase valued at 40 kcal of ME/kg (CD0), CD0 + β-mannanase (0.3 g/kg valued at 30 kcal of ME/kg) (CD70), CD0 + β-mannanase (0.3 g/kg valued at 45 kcal of ME/kg) (CD85), and CD0 + β-mannanase (0.3 g/kg valued at 60 kcal of ME/kg) (CD100). Growth performance was not affected in pigs fed ME-reduced diets containing β-mannanase. Pigs with CD100 had lower serum IL-1β concentration, and higher IL-10 was observed in pigs on CD0 than those fed β-mannanase. Coefficients of ATTD, and ATTD of DM and CP were higher in animals fed CD85 or CD100. Pigs with CD85 had higher alpha diversity richness but lower Firmicutes:Bacteroidota ratio. Acidaminococcaceae and Ruminococcaceae were more abundant in pigs fed CD0, but lower for Christensenellaceae NSJ-63 and NSJ-63 sp014384805. Pigs in CD85 showed higher Bacteroidaceae and Prevotella abundance, and lower for Streptococcaceae and Streptococcus. In conclusion, supplementation of β-mannanase in diets containing xylanase-phytase saved 85 to 100 kcal of ME/kg by supporting growth performance and improving nutrient digestibility in grower pigs.


[HIV and dentistry. Part 3. HIV infection: pathogenesis, epidemiology, definitions and classification].
The acquired immunodeficiency syndrome (AIDS) is caused by a retrovirus, the human immunodeficiency virus (HIV), that selectively deteriorates cell-mediated immunity. Consequently fatal opportunistic infections and/or malignancies occur. In this paper the pathogenesis and the epidemiology of HIV infection are described. In addition the 1993 revised classification for HIV infection and the expanded surveillance case definition for AIDS are presented.


Characterization of Klebsiella granulomatis pathogenic to silkworm, Bombyx mori L.
Bacterial disease of silkworm causes significant reduction of silk production leading to huge economic loss. This study aims to isolate bacteria from diseased silkworm and to determine its pathogenicity and antibiotic resistance. A strain of Klebsiella granulomatis has been isolated from silkworm haemolymph which was later identified on the basis of biochemical tests and 16S rRNA gene sequencing. The optimum culture condition of K. granulomatis was determined at pH 7.0 and 37 °C temperature. The strain was resistant to most of the antibiotics used in this study except azithromycin, gentamycin and ciprofloxacin. The strain is capable to reproduce flacherrie like symptoms with high mortality rate when re-injected into healthy silkworm. Treatment with low dose of ciprofloxacin was found to be effective to prevent flacherrie induced by the isolated K. granulomatis strain.


Network Pharmacology-based Prediction and Verification of Shikonin for Treating Colorectal Cancer.
Shikonin (SKN), a naturally occurring naphthoquinone, is a major active chemical component isolated from Lithospermum erythrorhizon Sieb Zucc, Arnebia euchroma (Royle) Johnst, or Arnebia guttata Bunge, and commonly used to treat viral infection, inflammation, and cancer. However, its underlying mechanism has not been elucidated. This study aims to explore the antitumor mechanism of SKN in colorectal cancer (CRC) through network pharmacology and cell experiments. SymMap database and Genecards were used to predict the potential targets of SKN and CRC, while the cotargets were obtained by Venn diagram. The cotargets were imported into the website of String and DAVID, constructing the protein-protein interaction (PPI) network, performing Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses, the Compound-Target-Pathway (C-T-P) network was generated by connecting potential pathways with the corresponding targets. According to the results of network pharmacological analysis, the cell experiments were used to verify the key signal pathway. The most relevant target of SKN for the treatment of CRC was PI3K/Akt signaling pathway. SKN inhibited CRC cells (HT29 and HCT116) proliferation, migration, and invasion, and promoted cell apoptosis by targeting IL6 and inhibiting the IL6R/PI3K/Akt signaling pathway. SKN promotes apoptosis and suppresses CRC cells' (HT29 and HCT116) activity through the PI3K-Akt signaling pathway. This research not only provided a theoretical and experimental basis for more in- -depth studies but also offered an efficient method for the rational utilization of a series of Traditional Chinese medicines as anti-CRC drugs.


Association between cardiovascular diseases and osteoporosis-reappraisal.
Positive association between cardiovascular diseases and osteoporosis is important because it concerns two major public health problems. Men and women with cardiovascular diseases (including severe abdominal aortic calcification (AAC) and peripheral arterial disease) tend to have lower areal and volumetric bone mineral density (BMD) as well as faster bone loss, although findings vary according to skeletal site. On one hand, severe forms of cardiovascular diseases (heart failure, myocardial infarction, hypertension, severe AAC) are associated with higher risk of osteoporotic fracture, especially hip fracture. This link was found in the studies based on healthcare databases and the cohort studies. On the other hand, low BMD, history of fragility fracture, vitamin D deficit and increased bone resorption are associated with higher risk of major cardiovascular events (myocardial infraction, stroke, cardiovascular mortality). Moreover, osteocalcin secreted by osteoblasts may be involved in the regulation of energetic and cardiovascular metabolism. The association between both pathologies depends partially on the shared risk factors, and also on the mechanisms that are involved in the regulation of bone and cardiovascular metabolism. Interpretation of the data should take into account methodological limitations: representativeness of the cohorts, quality of the registers and the information obtained from questionnaires, severity of diseases, number of events (statistical power) and their temporal closeness, availability of the information on potential confounders. It seems that patients with severe form of osteoporosis would benefit from assessment of the cardiovascular status and vice versa. However, official guidelines for the clinical practice are still lacking.


18F-PSMA-1007 multiparametric, dynamic PET/CT in biochemical relapse and progression of prostate cancer.
Aim of the present analysis is to investigate the biodistribution and pharmacokinetics of the recently clinically introduced radioligand 18F-PSMA-1007 in patients with biochemical recurrence or progression of prostate cancer (PC) by means of multiparametric (dynamic and whole-body) PET/CT. Twenty-five (25) patients with PC biochemical relapse or progression (median age = 66.0 years) were enrolled in the analysis. The median PSA value was 1.2 ng/mL (range = 0.1-237.3 ng/mL) and the median Gleason score was 7 (range = 6-10). All patients underwent dynamic PET/CT (dPET/CT) scanning (60 min) of the pelvis and lower abdomen as well as whole-body PET/CT with 18F-PSMA-1007. PET/CT assessment was based on qualitative evaluation, SUV calculation, and quantitative analysis based on a two-tissue compartment model and fractal analysis. 15/25 patients were PET-positive. Plasma PSA values in the 18F-PSMA-1007 positive group were higher (median = 3.6 ng/mL; range = 0.2-237.3 ng/mL) than in the 18F-PSMA-1007 negative group (median value = 0.7 ng/mL; range = 0.1-3.0 ng/mL). Semi-quantitative analysis in the PC lesions demonstrated a mean SUVaverage = 25.1 (median = 15.4; range = 3.5-119.2) and a mean SUVmax = 41.5 (median = 25.7; range = 3.8-213.2). Time-activity curves derived from dPET/CT revealed an increasing tracer accumulation during the 60 min of dynamic PET acquisition into the PC lesions, higher than in the urinary bladder and the colon. Significant correlations were observed between 18F-PSMA-1007 uptake (SUV), influx, and fractal dimension (FD). 18F-PSMA-1007 PET/CT could detect PC lesions in 60% of the patients of a mixed population, including also patients with very low PSA values. Higher PSA values were associated with a higher detection rate. Dynamic PET analysis revealed an increasing tracer uptake during the dynamic PET acquisition as well as high binding and internalization of the radiofluorinated PSMA ligand in the PC lesions.


A comparison of methods for analysis of mRNA in hematopoietic cells: conventional and clonal northern analysis and in situ hybridization.
Three methods for the detection of mRNA in hematopoietic cells are addressed, and examples using these techniques to examine human leukemic cells' genetic response to chemical and biological response modifiers shown. The limitations and specific applications of the three techniques are discussed.


The relationship between obesity and coronary artery disease.
Obesity continues to be a growing issue in the United States, with an estimated prevalence of 72 million people. There are major health implications associated with obesity, including its relationship with hypertension, diabetes mellitus type 2, metabolic syndrome, and dyslipidemia, all independent risk factors for coronary artery disease (CAD). Despite the increased risk of developing CAD, in recent years an "obesity paradox" has been described in which moderately obese individuals with established cardiovascular disease, including CAD, appear to have mortality similar to their normal-weight counterparts. This review examines the relationship between obesity and CAD, including the increased risk of hypertension, diabetes mellitus, metabolic syndrome, and dyslipidemia, along with a discussion of the obesity paradox and the benefits of weight reduction.


Thyroid stimulating hormone levels rise after assisted reproductive technology.
The goal of this study was to determine whether high E2 levels after controlled ovarian hyperstimulation affect TSH. Patients completing ART cycles between April-October 2010 were eligible for this cohort study. 180 patients were recruited however those with known thyroid disease were excluded. The final analysis included 154 subjects. Blood was collected at each visit during the ART cycle as well as at the pregnancy test. Samples were frozen at -20 °C and analyzed together for E2 and TSH using the same assay kit once all patients had completed their cycles. All participants were treated at the McGill University Health Center. A paired t-test was used to study the difference in TSH levels recorded at maximal and minimal Estradiol levels during ovarian stimulation. Multiple regression analysis was then used to determine if factors such as anti-thyroid antibodies and ovarian reserve measures affect this change in TSH. We used multiple imputation methods to account for missing data. As E2 levels rose from low to supra-physiologic levels during treatment, TSH levels also rose significantly. This increase was clinically significant by the time of pregnancy test. The factors that potentially affected the change in TSH were: male factor/tubal factor infertility, type of protocol used as well as the presence of thyroid antibodies. Although TSH increases during ART, this change only becomes clinically significant on the day of pregnancy test. Future studies should examine TSH changes specifically in certain "at-risk" sub-groups such as those with antibodies and known thyroid disease.


Incidence of cytomegalovirus UL97 and UL54 amino acid substitutions detected after 100 or 200 days of valganciclovir prophylaxis.
The IMPACT study was a randomized, double-blind study comparing 100 to 200 days of VGCV prophylaxis (900 mg once daily) in D+/R- kidney transplant recipients. Although extending the duration of prophylaxis resulted in a significant reduction in confirmed cytomegalovirus (CMV) disease (100-day: 36.8% vs 200-day: 16.1%(1)), the consequence of extending the duration of prophylaxis on the development of viral resistance remains unknown. To determine whether extending valganciclovir prophylaxis from 100 days to 200 days increased the incidence of ganciclovir resistance. Genotypic analysis of CMV UL97 and UL54 was conducted on virus isolated from patients meeting the predefined resistance analysis criteria (RAC). A greater number of patients met the RAC in the 100 day prophylaxis arm (50/163; 31%) compared to the 200 day prophylaxis arm (22/155; 14%). Sequence data were successfully generated for all 200-day patients and 48/50 100-day patients. Three patients in each treatment arm (100 day: 3/163 (1.8%) vs 200 day: 3/155 (1.9%)) had a single known valganciclovir resistance mutation detected (100 day: UL97 gene: M460V, C592G twice; 200 day: UL97 gene: C603W, M460V and UL54 gene: P522S). Overall, a resistance mutation was more likely to be detected if the patient met the RAC during prophylaxis (5/12 (42%)) compared to post-prophylaxis (1/58 (2%)). All six patients with known ganciclovir resistance mutations cleared the virus; three cleared virus without treatment and three cleared virus following treatment. Extending valganciclovir prophylaxis from 100 days to 200 days did not significantly affect the incidence of ganciclovir resistance.


[UroLift®: an operative non-ablative procedure for treatment of benign prostatic syndrome].
The implantation of a tissue retractor (UroLift®, Neotract, Pleasanton, CA) allows for the first time as a non-ablative operative technique, moderate deobstruction without removal or destruction of prostate tissue. The achievable treatment results are at least comparable to drug therapy with respect to alleviation of suffering and symptoms (primary treatment aim) and superior with respect deobstruction. The advantage of this method compared to all other conservative and operative therapy procedures is preservation of sexual function. An evaluation of this method is currently being carried out and compared to TURP in prospective, randomized studies (BPH6 study) and the results are expected in 2015.


Effect of phosphatidylserine on acetylcholine release and content in cortical slices from aging rats.
Cortical slices were prepared from male rats 3 to 28 months old. The slices were superfused with choline-enriched Krebs solution containing physostigmine and electrically stimulated at frequencies of 1, 2 and 5 Hz for 5 min periods preceded and followed by rest periods. The amount of acetylcholine released during the stimulation periods was quantified by bioassay. In some experiments acetylcholine content was measured at the end of the superfusion period in stimulated and unstimulated slices. The evoked acetylcholine release was constant between 3 and 11 months of age at each frequency tested and showed a 50% decrease between 11 and 14 months of age with no further decrease up to 28 months. No difference in the evoked acetylcholine release was detected between 3 and 16 month old rats if the old rats were pretreated with phosphatidylserine 15 mg/kg IP for at least 7 days. The effect of phosphatidylserine lasted for 5 days after interruption of the treatment. There was no difference in acetylcholine content between the stimulated and unstimulated slices in 3 month old rats. In 16 month old rats stimulation brought about a 44% decrease in acetylcholine content. This decrease did not occur in rats pretreated with phosphatidylserine for 7 days. Phosphatidylserine appears to restore acetylcholine release in aging rats by maintaining an adequate acetylcholine supply in the slices.


Comparison of low-density arrays, RT-PCR and real-time TaqMan RT-PCR in detection of grapevine viruses.
Low-density arrays (LDA) have been designed based on the real-time RT-PCR (TaqMan) assays for the specific detection of 13 viruses that infect Grapevines in addition to the housekeeping gene 18S rRNA. The viruses included in the study are Grapevine leafroll associated viruses 1, 2, 3, 4, 5, and 9, Grapevine leafroll associated virus-2 Redglobe (GLRaV-2RG) strain, Ruspestris stem pitting associated virus, Grapevine vitivirus A, Grapevine vitivirus B, Grapevine fanleaf virus, Tomato ringspot virus (ToRSV), and Grapevine fleck virus (GFkV). This study includes three new TaqMan RT-PCR assays that have been developed for GLRaV-2RG, GFkV and ToRSV and have been included in the TaqMan RT-PCR and LDA detection. The LDAs were evaluated against a wide range of isolates distributed geographically. Geographical locations included Africa, Europe, Australia, Asia, Latin America and the United States. High-throughput detection of these viruses using LDAs was compared to RT-PCR and real-time TaqMan RT-PCR. The efficiency of different RNA extraction methodologies and buffers were compared for use in low-density array detection. In addition improving the RNA extraction technique and testing the quality of the RNA using the 18S ribosomal RNA TaqMan assay as an RNA specific internal control proved to generate better diagnostic assays. This is the first report on the use of LDA for the detection of plant viruses.