Untangling the dynamics of persistence and colonization in microbial communities.
A central goal of community ecology is to infer biotic interactions from observed distributions of co-occurring species. Evidence for biotic interactions, however, can be obscured by shared environmental requirements, posing a challenge for statistical inference. Here, we introduce a dynamic statistical model, based on probit regression, that quantifies the effects of spatial and temporal covariance in longitudinal co-occurrence data. We separate the fixed pairwise effects of species occurrences on persistence and colonization rates, a potential signal of direct interactions, from latent pairwise correlations in occurrence, a potential signal of shared environmental responses. We first validate our modeling framework with several simulation studies. Then, we apply the approach to a pressing epidemiological question by examining how human papillomavirus (HPV) types coexist. Our results suggest that while HPV types respond similarly to common host traits, direct interactions are sparse and weak, so that HPV type diversity depends largely on shared environmental drivers. Our modeling approach is widely applicable to microbial communities and provides valuable insights that should lead to more directed hypothesis testing and mechanistic modeling.


[Chronic non-progressive form of chorea].
This is a report on a 65-year-old man with a 58-year-long history of choreic hyperkinesis with a wave-like course of the disease without its progression and without the development of intellectual disturbances. The authors discusses whether it is justified nosologically (in view of similar reports in the foreign literature) to refer this case to a distinctive form of nonprogressive chronic hereditary chorea distinctive from Huntington's chorea.


INTERACTION BETWEEN CRYSTALLINE PENICILLIN AND HUMAN PLASMA PROTEINS.
Penicillin combines with human serum albumin, as demonstrated by dialysis experiments. Unlike the sulfonamfide-albumin complex, the penicillin-albumin possesses antibiotic activity. Such a complex can be freed of unbound penicillin by repeated precipitation at 50 per cent. alcohol and obtained as a dried powder. Mouse excretion studies indicated that the penicillin-albumin complex was excreted more slowly than the sodium salt of penicillin.


Suffering, silence, and status: the importance and challenges of qualitative research on AIDS orphanhood.
Drawing on ethnographic fieldwork with Ugandan children affected by AIDS conducted from 2007 to 2014, this report summarizes findings of a study conducted to better understand the ways children experience orphanhood at the hands of HIV/AIDS. Three crucial, interrelated concepts emerged: suffering, silence, and status. This study explored the social context of AIDS orphanhood as both a cause of social suffering and a context for the suffering of individual children. Though problematic, silence about suffering is often due to continuing HIV/AIDS stigma in Uganda that makes one's status unspeakable, in spite of the adverse effect this has on the social order and efforts to eradicate the disease. Approaching silence as a distinct form of communication rather than an absence of it, the report considers silence's intergenerational functions, its detriments, and its consolations, in the context of HIV/AIDS-affected children's lives. In doing so, it also highlights the need for more child-centered, qualitative research on AIDS' psychosocial effects on children, despite the challenges of doing such research.


Localization and expression of MreB in Vibrio parahaemolyticus under different stresses.
MreB, the homolog of eukaryotic actin, may play a vital role when prokaryotes cope with stress by altering their spatial organization, including their morphology, subcellular architecture, and localization of macromolecules. This study investigates the behavior of MreB in Vibrio parahaemolyticus under various stresses. The behavior of MreB was probed using a yellow fluorescent protein-MreB conjugate in merodiploid strain SC9. Under normal growth conditions, MreB formed helical filaments in exponential-phase cells. The shape of starved or stationary-phase cells changed from rods to small spheroids. The cells differentiated into the viable but nonculturable (VBNC) state with small spherical cells via a "swelling-waning" process. In all cases, drastic remodeling of the MreB cytoskeleton was observed. MreB helices typically were loosened and fragmented into short filaments, arcs, and spots in bacteria under these stresses. The disintegrated MreB exhibited a strong tendency to attach to the cytoplasmic membrane. The expression of mreB generally declined in bacteria in the stationary phase and under starvation but was upregulated during the initial periods of cold shock and VBNC state differentiation and decreased afterwards. Our findings demonstrated the behavior of MreB in the morphological changes of V. parahaemolyticus under intrinsic or extrinsic stresses and may have important implications for studying the cellular stress response and aging.


A quantitative real-time PCR method using an X-linked gene for sex typing in pigs.
At present, a wide range of molecular sex-typing protocols in wild and domestic animals are available. In pigs, most of these methods are based on PCR amplification of X-Y homologous genes followed by gel electrophoresis which is time-consuming and in some cases expensive. In this paper, we describe, for the first time, a SYBR green-based quantitative real-time PCR (qPCR) assay using an X-linked gene, the glycoprotein M6B, for genetic sexing of pigs. Taking into account the differences in the glycoprotein M6B gene copy number between genders, we determine the correct sex of 54 pig samples from either diaphragm or hair follicle from different breeds using the 2(-ΔΔCT) method for relative quantification. Our qPCR assay represents a quick, inexpensive, and reliable tool for sex determination in pigs. This new protocol could be easily adapted to other species in which the sex determination was required.


[Sexual function of male rats exposed to the factors of the Chernobyl exclusion zone].
The influence of chronic internal and external irradiation in low doses on sexual behavior and fertility of sexual active animals keeping within the 30-km Chernobyl exclusion zone was studied. After the 1.5 month consumption of drinking water containing radionuclides of natural Chernobyl spectrum the decrease in proportion of sexual active animals and suppression of sexual motivation and erection were observed. This deviations resulted in the reducing of the inseminated females number. The dependence between the magnitude of total absorbed dose and the working of the sexual behavior regulative mechanisms was obtained. In addition, the reduction of rat fertility took place because of the increase of preimplantation, but not post-implantation death in in irradiated females coupled with irradiated males. The irradiation of males with total absorbed dose on testis 0.23 cGy decreased the fertility because of sexual behavior disturbance, and this effect was intensified by negative influence of ionizing radiation in the range of 0.7-7.0 cGy on male gametes.


The prognostic value of the AgNOR parameter in human breast cancer depends on the pRb and p53 status.
The amount of argyrophilic nucleolar organiser regions (AgNORs) represents a cell kinetics parameter used in tumour pathology for prognostic purposes. AgNOR expression is directly related to the rate of ribosome biogenesis, which has been recently shown to be controlled also by the tumour suppressor proteins pRb and p53. To ascertain the relative prognostic value of AgNORs and of pRb and p53 expression in breast carcinoma. This study was carried out on 335 human primary breast carcinomas with a median follow up time of 108 months. AgNORs were measured by morphometric analysis on sections that had been selectively silver stained; expression of p53 and phosphorylated and non-phosphorylated pRb forms was assessed by immunohistochemistry. Patients were divided into groups with low (249) and high (86) AgNOR values; with normal (267) and mutated p53 (68); and with normal (256) and hyperphosphorylated or deleted pRb (79). Univariate analysis of disease free survival showed that AgNORs and the status of pRb and p53 were significantly related to the patients' clinical outcome. However, among the four groups characterised by different pRb and p53 status, the AgNOR parameter was not capable of distinguishing subgroups of patients with different clinical outcomes. These findings indicate that the prognostic value of the AgNOR parameter depends on the status of the tumour suppressor proteins pRb and p53, and it cannot be ascribed to the relation between AgNORs and the cell proliferation rate.


Acute single channel EEG predictors of cognitive function after stroke.
Early and accurate identification of factors that predict post-stroke cognitive outcome is important to set realistic targets for rehabilitation and to guide patients and their families accordingly. However, behavioral measures of cognition are difficult to obtain in the acute phase of recovery due to clinical factors (e.g. fatigue) and functional barriers (e.g. language deficits). The aim of the current study was to test whether single channel wireless EEG data obtained acutely following stroke could predict longer-term cognitive function. Resting state Relative Power (RP) of delta, theta, alpha, beta, delta/alpha ratio (DAR), and delta/theta ratio (DTR) were obtained from a single electrode over FP1 in 24 participants within 72 hours of a first-ever stroke. The Montreal Cognitive Assessment (MoCA) was administered at 90-days post-stroke. Correlation and regression analyses were completed to identify relationships between 90-day cognitive function and electrophysiological data, neurological status, and demographic characteristics at admission. Four acute qEEG indices demonstrated moderate to high correlations with 90-day MoCA scores: DTR (r = -0.57, p = 0.01), RP theta (r = 0.50, p = 0.01), RP delta (r = -0.47, p = 0.02), and DAR (r = -0.45, p = 0.03). Acute DTR (b = -0.36, p < 0.05) and stroke severity on admission (b = -0.63, p < 0.01) were the best linear combination of predictors of MoCA scores 90-days post-stroke, accounting for 75% of variance. Data generated by a single pre-frontal electrode support the prognostic value of acute DAR, and identify DTR as a potential marker of post-stroke cognitive outcome. Use of single channel recording in an acute clinical setting may provide an efficient and valid predictor of cognitive function after stroke.


The role of inflammatory cytokines in endothelial dysfunction.
Clinical and experimental data support a link between endothelial dysfunction and inflammation. Inflammatory cytokines are important protagonists in formation of atherosclerotic plaque, eliciting effects throughout the atherosclerotic vessel. Importantly, the development of atherosclerotic lesions, regardless of the risk factor, e.g., diabetes, hypertension, obesity, is characterized by disruption in normal function of the endothelial cells. Endothelial cells, which line the internal lumen of the vasculature, are part of a complex system that regulates vasodilation and vasoconstriction, growth of vascular smooth muscle cells, inflammation, and hemostasis, maintaining a proper blood supply to tissues and regulating inflammation and coagulation. Current concepts suggest that the earliest event in atherogenesis is endothelial dysfunction, manifested by deficiencies in the production of nitric oxide (NO) and prostacyclin. The focus of this review is to summarize recent evidence showing the effects of inflammation on vascular dysfunction in ischemic-heart disease, which may prompt new directions for targeting inflammation in future therapies.


Identification of novel antioxidant collagen peptides for preventing and treating H2 O2 -induced oxidative stress in HepG2 cells through in vitro and in silico approaches.
Nowadays, the prevalence of oxidative stress-related chronic diseases is increasing. The identification of novel antioxidant collagen peptides to counteract oxidative stress for individuals' health has gained significant attention. In this study, collagen peptides with antioxidant activities were separated and identified by ion chromatography, reversed-phase high-performance liquid chromatography and liquid chromatography-tandem mass spectrometry. The identified antioxidant collagen peptides were further screened by molecular docking for Keap1-targeted peptide inhibitors and their theoretical interaction mechanisms were investigated. Four novel antioxidant collagen peptides, GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA, with high binding affinity to Keap1 were selected. Molecular docking results demonstrated that the putative antioxidant mechanism of the four antioxidant collagen peptides contributed to their blockage of Keap1-Nrf2 interactions. The results of antioxidant activity of the four antioxidant collagen peptides proved that IDGRPGPIGPA exerted a high scavenging capacity for DPPH and ABTS free radicals, while GPAGPpGPIG improved the resistance of cells to hydrogen peroxide-induced oxidative damage by promoting the activation of intracellular antioxidant enzymes and the production of reduced glutathione in human hepatoma (HepG2) cells. The antioxidant collagen peptides (GPAGPIGPVG, GPAGPpGPIG, ISGPpGPpGPA and IDGRPGPIGPA) will be developed as novel functional food for human health in the near future. © 2023 Society of Chemical Industry.


Study on the relation of the characteristics of the capture sites with the Leptospira spp. occurrence in bats and rodents from Yucatan, Mexico.
This study aims to describe the natural Leptospira occurrence in small mammals from Yucatan, Mexico, and to explore the relation between the characteristics of the capture sites and the Leptospira occurrence. Bats and rodents were captured in five sites of Yucatan state, and from them, a kidney fragment was collected that was used in the genomic DNA extraction. Leptospira DNA was identified by PCR targeting the 16S-rRNA and LipL32 genes. Additionally, a bioinformatic analysis was carried out to know the Leptospira species and was corroborated with a phylogenetic tree. The assemblage of small mammals was compound of 82 (51.2 %) bats and 78 (48.8 %) rodents. A global frequency (bats plus rodents) of Leptospira occurrence of 21.2 % (34/160) was observed; in bats, it was 21.9 % (18/82), and in rodents, 20.5 % (16/78). The phylogenetic trees based on LipL32 gene showed that the recovered sequences most closely resemble the species L. borgpetersenii and L. noguchii. The ordination of the capture sites with tropical deciduous forests as original vegetation is more related to the abundance of Leptospira-infected rodents. The ordination of the capture sites with tropical sub-deciduous forests as original vegetation is more related to the diversity of Leptospira-infected bat species. The canonical ordering of the capture sites is by the original vegetation type and the diversity and abundance of Leptospira-infected bat and rodent species.


Interactions between macrophage membrane and lipid mediators during cardiovascular diseases with the implications of scavenger receptors.
The onset and progression of cardiovascular diseases with the major underlying cause being atherosclerosis, occur during chronic inflammatory persistence in the vascular system, especially within the arterial wall. Such prolonged maladaptive inflammation is driven by macrophages and their key mediators are generally attributed to a disparity in lipid metabolism. Macrophages are the primary cells of innate immunity, endowed with expansive membrane domains involved in immune responses with their signalling systems. During atherosclerosis, the membrane domains and receptors control various active organisations of macrophages. Their scavenger/endocytic receptors regulate the trafficking of intracellular and extracellular cargo. Corresponding influence on lipid metabolism is mediated by their dynamic interaction with scavenger membrane receptors and their integrated mechanisms such as pinocytosis, phagocytosis, cholesterol export/import, etc. This interaction not only results in the functional differentiation of macrophages but also modifies their structural configurations. Here, we reviewed the association of macrophage membrane biomechanics and their scavenger receptor families with lipid metabolites during the event of atherogenesis. In addition, the membrane structure of macrophages and the signalling pathways involved in endocytosis integrated with lipid metabolism are detailed. This article establishes future insights into the scavenger receptors as potential targets for cardiovascular disease prevention and treatment.


Bench-to-bedside review: distal airways in acute respiratory distress syndrome.
Distal airways are less than 2 mm in diameter, comprising a relatively large cross-sectional area that allows for slower, laminar airflow. The airways include both membranous bronchioles and gas exchange ducts, and have been referred to in the past as the 'quiet zone', in part because these structures were felt to contribute little to lung mechanics and in part because they were difficult to study directly. More recent data suggest that distal airway dysfunction plays a significant role in acute respiratory distress syndrome. In addition, injurious mechanical ventilation strategies may contribute to distal airway dysfunction. The presence of elevated airway resistance, intrinsic positive end-expiratory pressure or a lower inflection point on a pressure-volume curve of the respiratory system may indicate the presence of impaired distal airway function. There are no proven specific treatments for distal airway dysfunction, and protective ventilation strategies to minimize distal airway injury may be the best therapeutic approach at this time.


The contribution of stressful life events throughout the life cycle to combat-induced psychopathology.
This study examines the contribution of prewar life events, war exposure, and postwar life events to combat-induced psychopathology among 425 Israeli War veterans from the Lebanon War. Data was collected at two time points (1983 and 2002). The sample included veterans with and without combat stress reaction (CSR). Battle intensity and subjective experience of risk in war were associated with CSR. Negative childhood life events, CSR, PTSD in 1983 and postwar negative life events were associated with PTSD in 2002. Furthermore, a path analysis revealed that CSR mediated the relation between battle intensity and PTSD in 2002. Our findings suggest that stressful life events throughout the life cycle contribute significantly to veterans' posttraumatic symptomatology, above and beyond combat exposure.


ST-segment elevation myocardial infarction – ideal scenario for bioresorbable vascular scaffold implantation?
Bioresorbable vascular scaffolds (BVS) represent a breakthrough technology for percutaneous coronary intervention (PCI). In this context, because of the unique properties of bioresorbable devices, ST-segment elevation myocardial infarction (STEMI) may represent the ideal scenario for BVS implantation. Consistently, 57% of physicians declare they currently use BVS in this group of patients. However, continuous and growing evidence on the good performance of these devices has been actually shown only in small studies with short- and mid-term follow-up. For these reasons, we need data from sufficiently large observational studies, with long-term follow-up, to confirm that BVS can deliver the same results as 2nd-generation drug-eluting stents when using an appropriate implantation technique. In this review, we discuss the potential advantages of BVS implantation in STEMI patients, together with the most recent evidence from clinical studies, highlighting safety and procedural concerns.


An Outlook on Lithium Ion Battery Technology.
Lithium ion batteries as a power source are dominating in portable electronics, penetrating the electric vehicle market, and on the verge of entering the utility market for grid-energy storage. Depending on the application, trade-offs among the various performance parameters-energy, power, cycle life, cost, safety, and environmental impact-are often needed, which are linked to severe materials chemistry challenges. The current lithium ion battery technology is based on insertion-reaction electrodes and organic liquid electrolytes. With an aim to increase the energy density or optimize the other performance parameters, new electrode materials based on both insertion reaction and dominantly conversion reaction along with solid electrolytes and lithium metal anode are being intensively pursued. This article presents an outlook on lithium ion technology by providing first the current status and then the progress and challenges with the ongoing approaches. In light of the formidable challenges with some of the approaches, the article finally points out practically viable near-term strategies.


Therapeutic value of small molecule inhibitor to plasminogen activator inhibitor-1 for lung fibrosis.
Fibrosis is a final stage of many lung diseases, with no effective treatment. Plasminogen activator inhibitor-1 (PAI-1), a primary inhibitor of tissue-type and urokinase-type plasminogen activators (tPA and uPA, respectively), plays a critical role in the development of fibrosis. In this study, we explored the therapeutic potential of an orally effective small molecule PAI-1 inhibitor, TM5275, in a model of lung fibrosis induced by transforming growth factor-β1 (TGF-β1), the most potent and ubiquitous profibrogenic cytokine, and in human lung fibroblasts (CCL-210 cells). The results show that an intranasal instillation of AdTGF-β1(223/225), an adenovirus expressing constitutively active TGF-β1, increased the expression of PAI-1 and induced fibrosis in murine lung tissue. On the other hand, treating mice with 40 mg/kg of TM5275 for 10 days, starting 4 days after the instillation of AdTGF-β1(223/225), restored the activities of uPA and tPA and almost completely blocked TGF-β1-induced lung fibrosis, as shown by collagen staining, Western blotting, and the measurement of hydroxyproline. No loss of body weight was evident under these treatment conditions with TM5275. Furthermore, we show that TM5275 induced apoptosis in both myofibroblasts (TGF-β1-treated) and naive (TGF-β1-untreated) human lung fibroblasts, and this apoptosis was associated with the activation of caspase-3/7, the induction of p53, and the inhibition of α-smooth muscle actin, fibronectin, and PAI-1 expression. Such an inhibition of fibrotic responses by TM5275 occurred even in cells pretreated with TGF-β1 for 6 hours. Together, the results suggest that TM5275 is a relatively safe and potent antifibrotic agent, with therapeutic potential in fibrotic lung disease.


Lost to follow up rate in the first year of ART in adults initiated in a universal test and treat programme: a retrospective cohort study in Ekurhuleni District, South Africa.
South Africa adopted and implemented the Universal Test and Treat (UTT) strategy for HIV since 2016. However, the care outcomes for patients initiated antiretroviral therapy (ART) through the UTT strategy have not been established. We determined the rate of lost to follow up (LTFU) and associated factors in patients who were initiated on ART through the UTT and the pre-ART strategy at 12 months post ART initiation. this retrospective study analyzed the records of a cohort of patients at 12 months post the initiation of ART. We extracted data from the TIER.Net electronic database of selected facilities in a sub-district in Gauteng Province, South Africa. Factors associated with LFTU at 12 months of ART were assessed and logistic regression performed to identify predictors of LFTU. records of 367 patients were evaluated, and 54% were initiated ART through the UTT strategy. The mean age was 36.3 years, mean CD4 cell count at ART initiation was 341 cells/mm3, and 25% were initiated at CD4 cell count above 500 cells/mm3. LTFU at 12 months was 28%, 50% were LFTU within six months, and 28% within three months of ART. LFTU in the UTT cohort was higher than in the pre-ART cohort, patients initiated through UTT were twice more likely to be LTFU (AOR = 1.84, CI: 1.13-3.00) than pre-ART patients. the rate of LTFU at 12 months of ART was 28%, which indicate that the retention in care rate (60%) falls far short of the triple 90 targets required for viral suppression.


[Topographic and cytoarchitectonics analysis of the vestibular complex in rats].
The limits of the vestibular nuclei and accessory groups were analyzed in 7 rats. This information was taken using camera lucida drawings of the vestibular nuclei and their neurons in serial sections. The study of the morphometric parameters of the neurons (area and maximum diameter) were accomplished by means of a program for image analysis. The cells of the superior nucleus had an area and maximum diameter of 302.05 microns2 and 24.05 microns, those of the medial nucleus 222.98 microns2 and 20.49 microns, those of the lateral nucleus 609.94 microns2 and 34.21 microns, and the descending nucleus cells 327.55 microns2 and 25.24 microns. The cellular parameters of the associated groups were also studied and the distribution of them in several intervals was established.


Contrast-induced nephropathy in patients undergoing emergency percutaneous coronary intervention for acute coronary syndrome.
Contrast-induced nephropathy (CIN) is associated with significantly increased morbidity and mortality after coronary angiography and percutaneous coronary intervention (PCI). The aim of the present study was to assess the clinical features and in-hospital outcomes of CIN after emergency PCI. The serum creatinine (SCr) concentration was measured from days 0 to 30 in 338 consecutive patients with acute coronary syndrome undergoing emergency PCI. CIN was defined as an increase in SCr of >25% or >0.5 mg/dl within 2 days after PCI. Overall, 94 patients (28%) developed CIN. The mean SCr on admission was not significantly different between patients with CIN and those without CIN. The CIN group had significantly greater SCr at days 1, 2, and 30 than did the no CIN group. Multivariate analysis showed female gender (odds ratio [OR] 2.38, 95% confidence interval [CI] 1.12 to 5.07, p = 0.025), a culprit lesion in the left anterior descending artery (OR 2.37, 95% CI 1.31 to 4.27, p = 0.0042), contrast agent volume >200 ml (OR 3.60, 95% CI 1.96 to 6.62, p <0.001) and end-diastolic pulmonary arterial pressure >15 mm Hg (OR 2.03, 95% CI 1.02 to 4.04, p <0.01) to all correlate independently with CIN. The in-hospital mortality rate was greater in the CIN group than in the no CIN group (9.6% vs 3.3%, respectively; p = 0.025). In conclusion, CIN is a frequent complication of emergency PCI for acute coronary syndrome and is associated with a greater mortality rate and persistent renal dysfunction.


Second-line systemic therapy for metastatic colorectal cancer.
The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016). There were no language or date of publication restrictions. Randomized controlled trials (RCTs) assessing the efficacy (survival, tumour response) and toxicity (incidence of severe adverse effects (SAEs)) of second-line systemic therapy (single or combined treatment with any anticancer drug, at any dose and number of cycles) in people with metastatic CRC that progressed, recurred or did not respond to first-line systemic therapy. Authors performed a descriptive analysis of each included RCT in terms of primary (survival) and secondary (tumour response, toxicity) endpoints. In the light of the variety of drug regimens tested in the included trials, we could carry out meta-analysis considering classes of (rather than single) anticancer regimens; to this aim, we applied the random-effects model to pool the data. We used hazard ratios (HRs) and risk ratios (RRs) to describe the strength of the association for survival (overall (OS) and progression-free survival (PFS)) and dichotomous (overall response rate (ORR) and SAE rate) data, respectively, with 95% confidence intervals (CI). Thirty-four RCTs (enrolling 13,787 participants) fulfilled the eligibility criteria. Available evidence enabled us to address multiple clinical issues regarding the survival effects of second-line systemic therapy of people with metastatic CRC.1. Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT; moderate-quality evidence); 2. modern chemotherapy (FOLFOX (5-fluorouracil plus leucovorin plus oxaliplatin), irinotecan) is more effective than outdated chemotherapy (5-fluorouracil) (HR for PFS: 0.59, 95% CI 0.49 to 0.73; 2 RCTs; high-quality evidence) (HR for OS: 0.69, 95% CI 0.51 to 0.94; 1 RCT; moderate-quality evidence); 3. irinotecan-based combinations were more effective than irinotecan alone (HR for PFS: 0.68, 95% CI 0.60 to 0.76; 6 RCTs; moderate-quality evidence); 4. targeted agents improved the efficacy of conventional chemotherapy both when considered together (HR for OS: 0.84, 95% CI 0.77 to 0.91; 6 RCTs; high-quality evidence) and when bevacizumab was used alone (HR for PFS: 0.67, 95% CI 0.60 to 0.75; 4 RCTs; high-quality evidence).With regard to secondary endpoints, tumour response rates generally paralleled the survival results; moreover, higher anticancer efficacy was generally associated with worse treatment-related toxicity, with the important exception of bevacizumab-containing regimens, where the addition of the targeted agent to chemotherapy did not result in a significant increase in the rate of SAE. Finally, we found that oral (instead of intravenous) fluoropyrimidines significantly reduced the incidence of adverse effects (without compromising efficacy) in people treated with oxaliplatin-based regimens.We could not draw any conclusions on other debated aspects in this field of oncology, such as ranking of treatments (not all possible comparisons have been tested and many comparisons were based on single trials enrolling a small number of participants) and quality of life (virtually no data available). Systemic therapy offers a survival benefit to people with metastatic CRC who did not respond to first-line treatment, especially when targeted agents are combined with conventional chemotherapeutic drugs. Further research is needed to define the optimal regimen and to identify people who most benefit from each treatment.


Bleomycin use in the treatment of Hodgkin lymphoma (HL): toxicity and outcomes in the modern era.
One-in-five Hodgkin Lymphoma (HL) patients treated with bleomycin develop bleomycin pulmonary toxicity (BPT). Given bleomycin-omission data with negative interim-PET, we assessed changes in BPT statistics. We retrospectively evaluated 126 ABVD-treated HL patients for overall survival (OS), progression-free survival (PFS), BPT factors, and management. Forty-seven patients developed BPT with 17% BPT-mortality. In univariable analysis, OS was negatively impacted by BPT (HR = 3.6, 95%CI = 1.2-10.6), but not bleomycin-omission (HR = 1.3, 95%CI = 0.5-3.7). In multivariable analysis, BPT was not associated with OS (HR = 3.0, 95%CI = 0.9-9.9). BPT patients were older (46 y vs 33 years) and received less bleomycin (107 vs 215 units) compared to non-BPT patients. BPT was managed primarily with bleomycin-omission. "Recent Era" patients had lower BPT rates (28% vs 48%), mortality (10% vs 21%), and bleomycin doses (7 vs 12 doses), yet higher bleomycin-omission in the absence of the BPT (59% vs 8%) compared to "Early Era". Our data suggest BPT continually impacts OS in ABVD-treated HL patients, however management is changing.


Effect of androstenedione administration on the maternal hypothalamo-pituitary-adreno-placental axis in the pregnant rhesus monkey.
To assess the interaction among androgens, placenta, and the hypothalamo-pituitary-adrenal axis we studied effects of androstenedione administered intravascularly to the pregnant monkey on maternal plasma CRH, ACTH, dehydroepiandrosterone sulfate (DHEAS), cortisol, and estradiol concentrations. Ten monkeys (128 +/- 3 days gestation; mean +/- SEM) were instrumented under general halothane anesthesia with maternal femoral artery and venous catheters and uterine electromyogram electrodes. At 137-144 days gestation, baseline maternal femoral artery samples for CRH, ACTH, DHEAS, cortisol, and estradiol measurements were taken at 1.5-h intervals for 7 h starting 2 h before darkness. On the following day, a continuous iv androstenedione infusion (0.3 mg/kg.min at 0.25 ml/h) in 10% intralipid was started at 0930 h in four monkeys; the other six animals received vehicle alone at the same rate starting at the same time. Maternal blood sampling was repeated 1 and 3 days after androstenedione or vehicle administration. Maternal plasma CRH, ACTH, DHEAS, cortisol, and estradiol levels were unaffected by intralipid. In contrast, androstenedione infusion produced a sustained increase in maternal plasma estradiol and a sustained fall in maternal plasma ACTH, but did not affect maternal plasma CRH, DHEAS, or cortisol concentrations. These results provide evidence for negative feedback regulation by androgens at the hypothalamo-pituitary-adrenal axis in the pregnant monkey. Lack of inhibition of maternal plasma CRH after androstenedione administration supports differential regulation of hypothalamic and placental CRH by androgens.


Proteomic mapping of differentially vulnerable pre-synaptic populations identifies regulators of neuronal stability in vivo.
Synapses are an early pathological target in many neurodegenerative diseases ranging from well-known adult onset conditions such as Alzheimer and Parkinson disease to neurodegenerative conditions of childhood such as spinal muscular atrophy (SMA) and neuronal ceroid lipofuscinosis (NCLs). However, the reasons why synapses are particularly vulnerable to such a broad range of neurodegeneration inducing stimuli remains unknown. To identify molecular modulators of synaptic stability and degeneration, we have used the Cln3 -/- mouse model of a juvenile form of NCL. We profiled and compared the molecular composition of anatomically-distinct, differentially-affected pre-synaptic populations from the Cln3 -/- mouse brain using proteomics followed by bioinformatic analyses. Identified protein candidates were then tested using a Drosophila CLN3 model to study their ability to modify the CLN3-neurodegenerative phenotype in vivo. We identified differential perturbations in a range of molecular cascades correlating with synaptic vulnerability, including valine catabolism and rho signalling pathways. Genetic and pharmacological targeting of key 'hub' proteins in such pathways was sufficient to modulate phenotypic presentation in a Drosophila CLN3 model. We propose that such a workflow provides a target rich method for the identification of novel disease regulators which could be applicable to the study of other conditions where appropriate models exist.


Dynamics of a parametrically excited simple pendulum.
The dynamics of a parametric simple pendulum submitted to an arbitrary angle of excitation ϕ was investigated experimentally by simulations and analytically. Analytical calculations for the loci of saddle-node bifurcations corresponding to the creation of resonant orbits were performed by applying Melnikov's method. However, this powerful perturbative method cannot be used to predict the existence of odd resonances for a vertical excitation within first order corrections. Yet, we showed that period-3 resonances indeed exist in such a configuration. Two degenerate attractors of different phases, associated with the same loci of saddle-node bifurcations in parameter space, are reported. For tilted excitation, the degeneracy is broken due to an extra torque, which was confirmed by the calculation of two distinct loci of saddle-node bifurcations for each attractor. This behavior persists up to ϕ≈7π/180, and for inclinations larger than this, only one attractor is observed. Bifurcation diagrams were constructed experimentally for ϕ=π/8 to demonstrate the existence of self-excited resonances (periods smaller than three) and hidden oscillations (for periods greater than three).


Injection technique for generating accurate adsorption isotherm data using the elution by characteristic points method.
With the use of the elution by characteristic points (ECP) method, the adsorption isotherms are rapidly determined from the diffusive part of an overloaded elution profile. However, very large injection volumes are required, which lead to extremely tailed rears of the injection profiles. The ECP method is based on a theory assuming rectangular injection profiles and can therefore not account for such profiles. Consequently, the use of the ECP method in the traditional way, with classical full-loop injections, results in serious errors on the determined adsorption isotherm parameters which has not been demonstrated until this study. Therefore, we developed and validated a new experimental injection method, here denoted the "cut-injection" technique where instead nearly rectangular injection profiles are generated. The result convincingly shows that adsorption isotherms acquired by using the new cut-injection technique nearly totally coincide with adsorption isotherms determined using the accurate reference methods.


Three metal ions at the active site of the Tetrahymena group I ribozyme.
Metal ions are critical for catalysis by many RNA and protein enzymes. To understand how these enzymes use metal ions for catalysis, it is crucial to determine how many metal ions are positioned at the active site. We report here an approach, combining atomic mutagenesis with quantitative determination of metal ion affinities, that allows individual metal ions to be distinguished. Using this approach, we show that at the active site of the Tetrahymena group I ribozyme the previously identified metal ion interactions with three substrate atoms, the 3'-oxygen of the oligonucleotide substrate and the 3'- and 2'-moieties of the guanosine nucleophile, are mediated by three distinct metal ions. This approach provides a general tool for distinguishing active site metal ions and allows the properties and roles of individual metal ions to be probed, even within the sea of metal ions bound to RNA.


Two useful tools: to improve patient engagement and transition from the hospital.
We use an Internet-based health assessment and feedback system to examine the range of needs and diverse experiences of 520 hospitalized adults in transition and the factors most strongly associated with their self-reported health confidence. Our results strongly suggest that patient engagement prior to admission and the quality of care coordination and communication during hospitalization can greatly enhance successful transition from the hospital back to the community. Hospitals are complex institutions. This report illustrates how the Internet or a straightforward graphic can make the complexity less overwhelming to patients and efficiently increase their health confidence for transitions.


Giant magnetoresistive biochip for DNA detection and HPV genotyping.
A giant magnetoresistive (GMR) biochip based on spin valve sensor array and magnetic nanoparticle labels was developed for inexpensive, sensitive and reliable DNA detection. The DNA targets detected in this experiment were PCR products amplified from Human Papillomavirus (HPV) plasmids. The concentrations of the target DNA after PCR were around 10 nM in most cases, but concentrations of 10 pM were also detectable, which is demonstrated by experiments with synthetic DNA samples. A mild but highly specific surface chemistry was used for probe oligonucleotide immobilization. Double modulation technique was used for signal detection in order to reduce the 1/f noise in the sensor. Twelve assays were performed with an accuracy of approximately 90%. Magnetic signals were consistent with particle coverage data measured with Scanning Electron Microscopy (SEM). More recent research on microfluidics showed the potential of reducing the assay time below one hour. This is the first demonstration of magnetic DNA detection using plasmid-derived samples. This study provides a direct proof that GMR sensors can be used for biomedical applications.


Dehydration-triggered shape morphing based on asymmetric bubble hydrogel microfibers.
Inspired by nature, scientists have been engaged in developing deformable artificial systems. Here, we propose an innovative method to realize controllable deformations using asymmetric bubble hydrogel microfibers produced by microfluidic cascaded coaxial devices. Asymmetric geometries, coupled with the mismatched shrinkage ratio, contribute to deformations upon dehydration. The dynamic process can be controlled by regulating bubble sizes, distances and packing modes. Various 4D structures have been constructed. Combined with the 3D printing technique, this proof-of-concept study may open new avenues for bio-engineering and beyond.


Cloning, sequencing and antigenic characterization of rVirB9 of Anaplasma marginale isolated from Paraná State, Brazil.
Anaplasma marginale, a tick-borne bacterium, causes bovine anaplasmosis responsible for significant economic losses in tropical and subtropical regions worldwide. Various major outer membranes have been described, and VirB9, a type IV secretion system protein, has been recently indicated as a candidate in vaccine development against anaplasmosis. The virB9 gene of an A. marginale strain isolated in Paraná, Brazil, was cloned by polymerase chain reaction and sequenced; its cloning into the pETSUMO vector produced a virB9-SUMO-6x His fusion gene construct. This recombinant clone was over-expressed in Escherichia coli BL21 (DE3), and the expressed fusion protein was solubilized with urea and purified with an Ni-NTA column. This method produced a relatively high yield of rVirB9. The deduced amino acid sequence encoded by VirB9 showed 99% homology to A. marginale isolates from St. Maries. rVirB9 was recognized by serum from cattle immunized with PR1 strain and by bovine sera infected with heterologous strains, showing that rVirB9 has conserved epitopes, which suggests that rVirB9 could be useful for the development of a vaccine against anaplasmosis.


Philip Hillkowitz The "Granddaddy of Medical Technologists" and Cofounder of the American Society for Clinical Pathologists and the Jewish Consumptives' Relief Society.
- In the early 20th century, the future of hospital-based clinical pathology practice was uncertain and this situation led to the formation of the American Society for Clinical Pathologists in 1922. Philip Hillkowitz, MD, and Ward Burdick, MD, were its cofounders. No biography of Hillkowitz exists. - To explore the life, beliefs, and accomplishments of Philip Hillkowitz. - Available primary and secondary historical sources were reviewed. - Hillkowitz, the son of a Russian rabbi, immigrated to America as an 11-year-old child in 1885. He later attended medical school in Cincinnati, Ohio, and then moved to Colorado, where he began his clinical practice, which transitioned into a clinical pathology practice. In Denver, he met Charles Spivak, MD, another Jewish immigrant and together they established the Jewish Consumptives' Relief Society, an ethnically sensitive tuberculosis sanatorium that flourished in the first half of the 20th century because of its national fundraising network. In 1921, Hillkowitz and Burdick, also a Denver-based pathologist, successively organized the pathologists in Denver, followed by the state of Colorado. Early the next year, they formed the American Society for Clinical Pathologists (ASCP). Working with the American College of Surgeons, the ASCP put hospital-based practice of clinical pathology on solid footing in the 1920s. Hillkowitz then established and oversaw the ASCP Board of Registry of Medical Technologists. - Philip Hillkowitz changed the directions of clinical pathology and tuberculosis treatment in 20th century America, while simultaneously serving as a successful ethnic power broker within both the American Jewish and Eastern European immigrant communities.


In vitro anti-oxidative activities of the various parts of Parkia biglobosa and GC-MS analysis of extracts with high activity.
The anti-oxidative activities of sequentially extracted solvent fractions of different parts of P. biglobosa were evaluated in a series of in vitro assays. Our findings indicated that all extracts had electron donating and free radical scavenging activities. But the ethanol (EtOH) extracts from all the parts demonstrated more promising anti-oxidative effects in these experimental models. Apart from the aqueous extracts of the stem bark and leaves, all other extracts exhibited hydroxyl radical scavenging (HRS) activity but the ethyl acetate (EtOAc) extract of the stem bark and EtOH extracts of the root and leaves possessed more powerful HRS activity than other corresponding extracts in the parts. Further, nitric oxide (NO) inhibition activities were observed in all the extracts except the EtOAc extract of the stem bark which showed pro-oxidative activity. However, the EtOH extract of the stem bark and root as well as the EtOAc extract of the leaves displayed more potent anti-NO activity than other extracts in the parts. The GC-MS analysis of the EtOH extracts revealed that the most abundant phytochemicals are pyrogallol derivatives. Data from this study suggest that the EtOH extracts from different parts of P. biglobosa contained potent anti-oxidative agents and pyrogallol could be the main bioactive constituent.


Influence of dietary genistein levels on tissue genistein deposition and on the physical, chemical, and sensory quality of rainbow trout, Oncorhynchus mykiss.
Genistein, the primary isoflavone in soybean, is one of the chemical components responsible for some of the off-flavors associated with soy-based foods. The potential effects of genistein on the sensory and chemical quality of fish muscle may affect the full utilization of soybean meal as an alternative protein in aquaculture diets. Fingerling trout fed commercial diets containing 0, 500, 1000, or 3000 ppm pure genistein were analyzed after 6 and 12 months of feeding. Genistein was extracted by enzymatic digestions in Tris buffer and quantified by high-performance liquid chromatography. Moisture, fat, protein, ash, and tristimulus color of the fillets were determined. The extent of lipid oxidation occurring in fillets harvested after 12 months of feeding was studied by measurements of thiobarbituric acid reactive substances (TBARS) after 4 and 8 days of refrigerated storage at 4 degrees C. Triangle tests were performed to determine if there were any detectable sensory differences. A dietary genistein content of 3000 ppm led to the deposition of approximately 5.4 pmol of genistein/mg of fillet. Triangle test panelists were unable to detect any significant (p < or = 0.05) differences between the fillets from trout fed the 0 and 3000 ppm genistein concentrations. Moisture, ash, and protein content were influenced by time of harvest, while color was unaffected. TBARS levels on days 4 and 8 were significantly (p < 0.05) higher in the fillets from the 0 ppm genistein level than in fillets from fish fed dietary genistein.


[Structural organization of the bioelectrical activity of the brain in neurotic children].
Using the method of computerized primary and factorial analysis of the EEGs in children with various neurotic disturbances, the authors obtained integral age-related characteristics, both common and specific, typical of these patients. The peculiarities of the age-specific pattern of integral characteristics of the EEG indicate that in patients aged 9-12 years the process of a diffuse decrease of the amplitude of the cortical rhythms was inhibited and that the period of the maximum intensity of theta-rhythm in the anterior central portions was displaced from the age 9-10 years to the age of 11-12 years. These disorders were most prominent in children with vegetative emotional disturbances.


Inversions in chromosome 10 of human thyroid cells induced by accelerated heavy ions.
Papillary thyroid carcinoma (PTC) is a known radiation-induced tumor. Rearrangements in human chromosome 10 and in particular intrachromosomal exchanges are often associated with PTC formation. In this study we measured intrachromosomal exchanges in human thyroid follicular cells exposed to sparsely or densely ionizing radiation. Assuming that inversions in chromosome 10 are a biomarker of PTC risk, we estimated the relative biological effectiveness (RBE) of heavy ions using a molecular marker in vitro. The analysis of chromosomal aberrations was performed with the mBAND technique, which allows detection of both inter- and intrachromosomal exchanges. Our results do not show any significant increase in the yield of intrachanges in samples exposed to heavy ions compared to X rays. Within the constraints imposed by the experimental model we used, we conclude that heavy ions would not necessarily be more effective than X rays in the induction of thyroid cancer.


CaSBP11 Participates in the Defense Response of Pepper to Phytophthora capsici through Regulating the Expression of Defense-Related Genes.
Squamosa promoter binding protein (SBP)-box genes are plant-specific transcription factors involved in plant growth and development, morphogenesis and biotic and abiotic stress responses. However, these genes have been understudied in pepper, especially with respect to defense responses to Phytophthora capsici infection. CaSBP11 is a SBP-box family gene in pepper that was identified in our previous research. Silencing CaSBP11 enhanced the defense response of pepper plants to Phytophthora capsici. Without treatment, the expression of defense-related genes (CaBPR1, CaPO1, CaSAR8.2 and CaDEF1) increased in CaSBP11-silenced plants. However, the expression levels of these genes were inhibited under transient CaSBP11 expression. CaSBP11 overexpression in transgenic Nicotiana benthamiana decreased defense responses, while in Arabidopsis, it induced or inhibited the expression of genes in the salicylic acid and jasmonic acid signaling pathways. CaSBP11 overexpression in sid2-2 mutants induced AtNPR1, AtNPR3, AtNPR4, AtPAD4, AtEDS1, AtEDS5, AtMPK4 and AtNDR1 expression, while AtSARD1 and AtTGA6 expression was inhibited. CaSBP11 overexpression in coi1-21 and coi1-22 mutants, respectively, inhibited AtPDF1.2 expression and induced AtPR1 expression. These results indicate CaSBP11 has a negative regulatory effect on defense responses to Phytophthora capsici. Moreover, it may participate in the defense response of pepper to Phytophthora capsici by regulating defense-related genes and the salicylic and jasmonic acid-mediated disease resistance signaling pathways.


Genomics approaches to study musical aptitude.
Although music and other forms of art can develop in diverse directions, they are linked to the genetic profiles of populations. Hearing music is a strong environmental trigger that serves as an excellent model to study the crosstalk between genes and the environment. We propose that the ability to enjoy and practice music requires musical aptitude, which is a common and innate trait facilitating the enjoyment and practice of music. The innate drive for music can only have arisen by exposure to music, and it develops with motivation and training in musically rich environments. Recent genomic approaches have shown that the genes responsible for inner ear development, auditory pathways and neurocognitive processes may underlay musical aptitude. It is expected that genomic approaches can be applied to musical traits and will reveal new biological mechanisms that affect human evolution, brain function, and civilisation.


Oritavancin for the treatment of acute bacterial skin and skin structure infections: an evidence-based review.
The emergence of resistance to glycopeptide antibiotics such as vancomycin and teicoplanin among Gram-positive bacteria has spurred the search for second-generation drugs of this class. Oritavancin, a promising novel, second-generation, semisynthetic lipoglycopeptide, is distinguished by two mechanisms of action: inhibition of cell wall synthesis and disruption of the cell membrane. This dual mechanism of action has increased the activity of oritavancin against vancomycin-resistant Gram-positive bacteria compared to other glycopeptides. Oritavancin has a concentration-dependent and rapid bactericidal activity against Gram-positive bacteria, particularly enterococci, contrary to vancomycin and teicoplanin, which exhibit bacteriostatic activity. It has a long half-life of about 195.4 hours and is slowly eliminated by the liver and kidneys, allowing once-daily dosing. Oritavancin has demonstrated preliminary safety and efficacy in Phase I and Phase II clinical trials. It was recently shown to be noninferior to vancomycin in a large Phase III randomized, double-blind clinical trial. To date, adverse events have been mild and limited, the most common being administration site complaints, headache, and nausea. Oritavancin appears to be a promising antimicrobial alternative to vancomycin with additional activity against Staphylococcus and Enterococcus isolates resistant to vancomycin and a more convenient way of administration.


Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunit GPA1 and cAMP.
This study explores signal transduction pathways that function during mating and infection in the opportunistic, human fungal pathogen Cryptococcus neoformans. The gene encoding a G-protein alpha subunit homolog, GPA1, was disrupted by homologous recombination. The gpa1 mutant strain was viable but exhibited a defect in mating in response to nitrogen starvation. Additionally, the gpa1 mutant strain failed to induce two well-established virulence factors-melanin synthesis, in response to glucose starvation; and capsule production, in response to iron limitation. As a consequence, virulence of the gpa1 mutant strain was significantly attenuated in an animal model of cryptococcal meningitis. Reintroduction of the wild-type GPA1 gene complemented the gpa1 mutant phenotypes and restored mating, melanin and capsule production, and virulence. Similarly, exogenous cAMP also suppressed the gpa1 mutant phenotypes, restoring mating and production of melanin and capsule. These observations support a model in which GPA1 has a role in sensing diverse environmental signals required for mating and virulence by regulating cAMP metabolism in C. neoformans.


Effect of SARS-CoV-2 infection on anti-HLA antibodies and de novo donor specific antibodies incidence in lung transplant recipients.
There are no clear guidelines on how to handle immunosuppression in lung transplant recipients (LTRs) infected by SARS-CoV-2. Antimetabolite reduction with corticosteroid escalation is the most frequent strategy. The aim of this study was to determine the effect of this therapeutic approach on the incidence of de novo donor specific-antibodies (dnDSA). We retrospectively analysed a cohort of 27 LTRs diagnosed with SARS-CoV-2 infection between September 2020 and April 2021 with available anti-HLA antibodies screening before and after infection. Managed as per the centre's SARS-CoV-2 protocol, the treatment modalities included specific virostatic treatment, convalescent plasma administration, reduction or discontinuation of mycophenolate and transient corticosteroid escalation initiated in the second week post-infection. All 27 patients received virostatics: 15 (55.6%) remdesivir and 12 (44.4%) favipiravir. In addition, 18 patients (66.7%) underwent convalescent plasma therapy. Of the 27 patients, 25 (92.6%) received mycophenolate as a part of their maintenance immunosuppressive regimen, which was temporarily reduced in 10 (37%) and discontinued in 15 LTRs (55.6%), the median resumption times for mycophenolate daily doses of at least 1000 mg being 13 days (IQR 11.0-63.5) and 59 days (IQR 26.0-130.0), respectively. Corticosteroids were escalated in 25 patients (92.6%), of whom 9 (33.3%) received IV methylprednisolone (median 80 mg/day; IQR 80-187.5) and 16 (59.3%) had oral prednisone adjusted (median 20 mg/day; IQR 16.3-38.8). The median time to revert to the corticosteroid dosage of ≤20 mg/day was 42 days (IQR 36.0-87.0). Notably, no dnDSA were detected in any LTR between 1 and 9 months from the onset of the SARS-CoV-2 infection. Our findings suggest that antimetabolite cessation with a transient corticosteroid escalation is a safe therapeutic strategy regarding anti-HLA dynamics in SARS-CoV-2 infected LTRs.


The Comparisons of Cerebral Hemodynamics Induced by Obstructive Sleep Apnea with Arousal and Periodic Limb Movement with Arousal: A Pilot NIRS Study.
Obstructive sleep apnea syndrome (OSA) and restless legs syndrome (RLS) with periodic limb movement during sleep (PLMS) are two sleep disorders characterized by repetitive respiratory or movement events associated with cortical arousals. We compared the cerebral hemodynamic changes linked to periodic apneas/hypopneas with arousals (AHA) in four OSA-patients with periodic limb movements (PLMA) with arousals in four patients with RLS-PLMS using near-infrared spectroscopy (NIRS). AHA induced homogenous pattern of periodic fluctuations in oxygenated (HbO2) and deoxygenated (HHb) hemoglobin, i.e., the decrease of HbO2 was accompanied by an increase of HHb during the respiratory event and resolved to reverse pattern when cortical arousal started. Blood volume (BV) showed the same pattern as HHb but with relative smaller amplitude in most of the AHA events.These changing patterns were significant as Wilcoxon signed-rank tests gave p < 0.001 when comparing the area under the curve of these hemodynamic parameters to zero. By contrast, in PLMA limb movements induced periodic increments in HbO2 and BV (Wilcoxon signed-rank tests, p < 0.001), but HHb changed more heterogeneously even during the events coming from the same patient. Heart rate (HR) also showed different patterns between AHA and PLMA. It significantly decreased during the respiratory event (Wilcoxon signed-rank test, p < 0.001) and then increased after the occurrence of cortical arousal (Wilcoxon signed-rank test, p < 0.001); while in PLMA HR first increased preceding the occurrence of cortical arousal (Wilcoxon signed-rank test, p < 0.001) and then decreased. The results of this preliminary study show that both AHA and PLMA induce changes in cerebral hemodynamics. The occurrence of cortical arousal is accompanied by increased HR in both events, but by different BV changes (i.e., decreased/increased BV in AHA/PLMA, respectively). HR changes may partially account for the increased cerebral hemodynamics during PLMA; whereas in AHA probable vasodilatation mediated by hypoxia/hypercapnia is more crucial for the post-arousal hemodynamics. The differences between changes of cerebral hemodynamics and HR may indicate different pathological mechanisms behind these two sleep disorder events.


[Young children with serious disorders as a result of late diagnosis of cystic fibrosis].
A girl and a boy, who both presented with recurrent respiratory infections from birth, were referred to a paediatrician at the age of 2.5 years: they were diagnosed with cystic fibrosis (CF). The girl died from respiratory insufficiency at the age of 6 years and the boy at the age of 13 years from pulmonary aspiration. A further girl and boy who presented with abnormal faeces and failure to thrive were referred to the paediatrician at the ages of 2.5 months with haematomas and 2 weeks with anaemia respectively, as a result of vitamin deficiencies due to malabsorption. They too had CF. The girl had a brain haemorrhage in the meantime that left her with serious impairments. The boy recovered. A delay in diagnosing CF is not uncommon, as the symptoms of CF are hard to differentiate from those of common childhood diseases. However, this diagnostic delay can result in serious organ damage. Current treatment of CF has a predominantly prophylactic character and aims at maintaining normal growth and nutritional status as well as at preventing or postponing chronic bacterial infection of the lower respiratory tract. This treatment is most effective when it is started before any organ damage has occurred: a state that can only be achieved when patients with CF are identified shortly after birth. Therefore, it is important to add CF-screening to the neonatal screening program.


Autoimmune Encephalitis with Autoantibodies to NMDAR1 following Herpes Encephalitis in Children and Adolescents.
Herpes simplex virus (HSV) type 1 is a frequent pathogen causing infectious encephalitis (HSVE). Early treatment with intravenous acyclovir has led to a significant decrease in mortality. However, especially in children, deterioration during or after HSVE may occur without any evidence of HSV reactivation or improvement following repeated antiviral therapy. Here, we report 15 patients (age range 3 months to 15 years) who suffered from autoimmune encephalitis with autoantibodies to NMDAR1 following Herpes encephalitis, presenting with movement abnormalities (young children) or neuropsychiatric symptoms (older children) as major complaints, respectively. The diagnosis was based on positive cerebrospinal fluid (CSF) and/or serum anti-NMDAR-antibodies with two children showing only positive CSF antibody findings. The time lag between first symptoms and diagnosis of autoimmune encephalitis was significantly longer than between first symptoms and diagnosis of HSVE (p <0.01). All patients improved during immunosuppressive treatment, during which plasmapheresis or rituximab treatments were applied in 11 patients, irrespective of their age. Despite immunotherapy, no patients relapsed with HSVE. Early diagnosis and treatment of autoimmune encephalitis after HSVE may be associated with a better outcome so that high clinical awareness and routine testing for anti-NMDAR-antibodies after HSVE seems advisable. If autoimmune encephalitis is suspected, antibody testing should also be performed on CSF if negative in serum.


Is maternal obesity a risk factor for anencephaly and spina bifida?
To determine whether the risk of having an infant with anencephaly or spina bifida is greater among obese women than among average-weight women, we compared 307 Atlanta-area women who gave birth to a liveborn or stillborn infant with anencephaly or spina bifida (case group) with 2,755 Atlanta-area women who gave birth to an infant without birth defects (control group). The infants of control women were randomly selected from birth certificates and frequency-matched to the case group by race, birth hospital, and birth period from 1968 through 1980. After adjusting for maternal age, education, smoking status, alcohol use, chronic illness, and vitamin use, we found that, compared with average-weight women, obese women (pregravid body mass index greater than 29) had almost twice the risk of having an infant with spina bifida or anencephaly (odds ratio = 1.9; 95% confidence limits = 1.1, 3.4). A woman's risk increased with her body mass index: adjusted odds ratios ranged from 0.6 (95% confidence limits = 0.3, 2.1) for very underweight women to 1.9 for obese women.


Primary liver transplantation and liver retransplantation: comparison of health-related quality of life and mental status - a cross-sectional study.
Liver Retransplantation (Re-LT) procedures are associated with an increased risk of morbidity and mortality. Up to date, there is no knowledge on the health-related quality of life and the mental status of these patients. Health-Related Quality of Life (HRQoL) was assessed by using the Short Form 36 (SF-36) Health Survey and Mental Status was assessed by using the Hospital Anxiety and Depression Scale (HADS). The patients were examined in different assessments: During regular check-up examinations in the LT outpatient department in 2011 (Survey 1) and in a postal survey in 2013 (Survey 2). Their medical data was collected by using an established database. We received eligible surveys of 383 patients (55.6%) with a history of LT, of which 15 (3.9%) had undergone Re-LT (Re-LT group). These patients were compared to a group of 60 patients who had undergone only one LT. With regard to their HRQoL, the Re-LT group had significantly lower scores on the scales of physical function (PF, p = 0.026), their role-physical (RP, p = 0.008), their vitality (VIT, p = 0.040), and their role-emotional (RE, p = 0.005). The scores for anxiety and depression did not differ significantly between the groups. In a multiple regression analysis, chronic kidney disease was found to be an independent risk factor for decreased scores of PF (p = 0.023). Patients who have to undergo Re-LT procedures are faceing impairments in physical aspects of a HRQoL. Together with clinical results from other studies, the findings of the present examination underline the need for an optimized organ distribution strategy since not all patients listed for Re-LT appear to benefit from it.


Removal of crystal violet from water by magnetically modified activated carbon and nanomagnetic iron oxide.
Magnetically modified activated carbon, which synthesized by nanomagnetic iron oxide, was used for fast and effective removal of Crystal Violet from aqueous solutions. The scanning electron microscopy (SEM) images of nano-adsorbent showed that the average sizes of adsorbent are less than 100 nm. The various parameters, affecting on adsorption process, were examined including pH and temperature of dye solution, dose of adsorbent, and contact time. Then, thermodynamic parameters of sorption were calculated. Langmuir and Freundlich isotherms were used to fit the resulting data. Adsorption kinetics was consistent with a pseudo second order equation. Thermodynamic parameters of adsorption, ∆H(0), and ∆S(0) were calculated. Also, for further investigations, nano magnetic iron oxides was synthesized and used as adsorbent. Sorption capacities were depending on the temperature varied from 44.7 to 67.1 mg/g and from 12.7 to 16.5 mg/g for magnetically modified activated carbon and nanomagnetic iron oxide, respectively.


Does dairy calcium intake enhance weight loss among overweight diabetic patients?
To examine the effect of dairy calcium consumption on weight loss and improvement in cardiovascular disease (CVD) and diabetes indicators among overweight diabetic patients. This was an ancillary study of a 6-month randomized clinical trial assessing the effect of three isocaloric diets in type 2 diabetic patients: 1) mixed glycemic index carbohydrate diet, 2) low-glycemic index diet, and 3) modified Mediterranean diet. Low-fat dairy product consumption varied within and across the groups by personal choice. Dietary intake, weight, CVD risk factors, and diabetes indexes were measured at baseline and at 6 months. A total of 259 diabetic patients were recruited with an average BMI >31 kg/m2 and mean age of 55 years. No difference was found at baseline between the intervention groups in CVD risk factors, diabetes indicators, macronutrient intake, and nutrient intake from dairy products. Dairy calcium intake was associated with percentage of weight loss. Among the high tertile of dairy calcium intake, the odds ratio for weight loss of >8% was 2.4, P = 0.04, compared with the first tertile, after controlling for nondairy calcium intake, diet type, and the change in energy intake from baseline. No association was noted between dairy calcium and other health indexes except for triglyceride levels. A diet rich in dairy calcium intake enhances weight reduction in type 2 diabetic patients. Such a diet could be tried in diabetic patients, especially those with difficulty adhering to other weight reduction diets.


Calcium signaling and secretory responses in endothelin-stimulated anterior pituitary cells.
Endothelin (ET) receptors are present in pituitary cells and stimulate hormone release through the phosphoinositide/Ca2+ signaling system. In pituitary cell suspensions, ET caused [Ca2+]i elevations of much higher amplitudes than those induced by other vasoactive hormones, including angiotensin II, vasopressin, and noradrenalin. The action of ET was coupled to rapid and transient activation of exocytosis in gonadotrophs, thyrotrophs, somatotrophs, and lactotrophs. In contrast, angiotensin II did not stimulate luteinizing hormone release, and luteinizing hormone responses to vasopressin and noradrenalin were very small. Single gonadotrophs exhibited three types of [Ca2+]i responses to increasing doses of ET, (a) subthreshold responses, with amplitude modulation; (b) threshold-oscillatory responses, with frequency modulation; and (c) threshold-biphasic responses, as the summation of single Ca2+ spikes. The same [Ca2+]i patterns were also seen in gonadotropin-releasing hormone (GnRH)-stimulated cells. In the presence of [Ca2+]e, the amplitudes of the Ca2+ spikes progressively decreased during continuous stimulation with ET or GnRH, reaching the nonoscillatory plateau level after 200-400 sec of stimulation. In cells stimulated with GnRH, subsequent exposure to ET, GnRH, or ionomycin during the plateau phase did not elicit further increases in [Ca2+]i, whereas cells stimulated with ET responded partially to all three agents. In addition, cells exposed to ET or GnRH for 30 min, followed by a 30-min recovery period, were able to mount a full [Ca2+]i response to GnRH, but not to ET-1. Similarly, both peptides elicited rapid increases in LH release, with comparable potencies, but the response to ET decreased much more rapidly during sustained stimulation and gonadotrophs became refractory to further ET stimulation. This is in part attributable to rapid endocytosis of ET receptors during continuous agonist stimulation. These data indicate that ET exerts potent but transient secretory actions in several pituitary cell types and is a potential regulator of gonadotropin release. The initial receptor-coupling events in both ET- and GnRH-stimulated cells are similar, but the differences observed during continuous or repetitive stimulation indicate that the ET receptor pathway undergoes rapid desensitization that is critical in determining the distinct cellular responses to the two peptides.


[Detection of mycobacterium tuberculosis DNA using nested polymerase chain reaction in lymph nodes with sarcoidosis, fixed in formalin and embedded in paraffin].
An involvement of mycobacteria in the pathogenesis of sarcoidosis has often been hypothesized, but not confirmed reproducibly. In this study we applied a nested Polymerase Chain Reaction (PCR) to the insertion sequence IS6110 for detection of Mycobacterium tuberculosis (MT) DNA in formalin-fixed and paraffin-embedded tissues from patients with sarcoidosis, with tuberculosis and atypical mycobacteriosis confirmed by culture, and from negative control samples. MT-DNA could be detected in 2/30 samples of sarcoidosis, in 10/10 tuberculoses, in 0/5 atypical mycobacterioses and in 0/10 negative controls. Nested PCR confirmed its high sensitivity and specificity in detecting MT-DNA on archival histopathological specimens. From our results we conclude that in the granulomatous lesions of sarcoidosis MT-DNA is only sporadically demonstrable and probably it doesn't play a role in the pathogenesis of this disease.


From numbers to understanding: the impact of demographic factors on seclusion rates.
The reduction and, where possible, elimination of seclusion has been recognized as a national safety priority for mental health services in Australia, with significant attention devoted to strategies to achieve this goal. The aim of this study was to compare specific demographic characteristics between consumers who have been secluded to those who have not. Patient data (n = 3244) collected by 11 mental health services across Australia for six months over a 12 month period were analysed using demographic statistics. A comparison was undertaken between those who were secluded one or more times (n = 271) and those who were not secluded (n = 2973). Differences were measured with the use of independent samples t-tests and chi-square statistics. Age, gender, diagnosis, indigenous status and Health of the National Outcomes Scores (HoNOS) were found to be significant factors in relation to seclusion. Men, younger people, and indigenous people were found to be more likely to be secluded. In addition, consumers who scored higher on the behaviour,impairment and social subscales of HoNOS were more likely to be secluded. Comparative analysis of demographic characteristics of secluded and non-secluded patients can provide vital information for consideration when planning and evaluating seclusion reduction strategies.


May Measurement Month 2017: an analysis of blood pressure screening results in Nepal-South Asia.
Hypertension is the leading risk factor of mortality in Nepal accounting for ∼33 000 deaths in 2016. However, more than 50% of the hypertensive patients are unaware of their status. We participated in the May Measurement Month 2017 (MMM17) project initiated worldwide by the International Society of Hypertension to raise the awareness on the importance of blood pressure (BP) screening. In this paper, we discuss the screening results of MMM17 in Nepal. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017 following the standard MMM protocol. Data were collected from 18 screening sites in 7 districts covering 5 provinces. Screenings were conducted either in health facilities, public places, or participants' homes. Trained volunteers with health science background and female community health volunteers were mobilized to take part in the screening. A total of 5972 individuals were screened and of 5968 participants, for whom a mean of the 2nd and 3rd readings was available, 1456 (24.4%) participants had hypertension; 908 (16.8%) of those not receiving treatment were hypertensive; and 248 (45.2%) of those being treated had uncontrolled BP. MMM17 is the first nationwide BP screening campaign undertaken in Nepal. Given the suboptimal treatment and control rates identified in the study, there is a strong imperative to scale up hypertension prevention, screening, and management programmes. These results suggest that opportunistic screening can identify significant numbers with hypertension. Mobilization of existing volunteer networks and support of community stakeholders, would be necessary to improve the overall impact and sustainability of future screening programmes.


Impact of 27-hydroxylase (CYP27A1) and 27-hydroxycholesterol in breast cancer.
The impact of systemic 27-hydroxycholesterol (27HC) and intratumoral CYP27A1 expression on pathobiology and clinical response to statins in breast cancer needs clarification. 27HC is an oxysterol produced from cholesterol by the monooxygenase CYP27A1, which regulates intracellular cholesterol homeostasis. 27HC also acts as an endogenous selective estrogen receptor (ER) modulator capable of increasing breast cancer growth and metastasis. 27HC levels can be modulated by statins or direct inhibition of CYP27A1, thereby attenuating its pro-tumorigenic activities. Herein, the effect of statins on serum 27HC and tumor-specific CYP27A1 expression was evaluated in 42 breast cancer patients treated with atorvastatin within a phase II clinical trial. Further, the associations between CYP27A1 expression with other primary tumor pathological features and clinical outcomes were studied in two additional independent cohorts. Statin treatment effectively decreased serum 27HC and deregulated CYP27A1 expression in tumors. However, these changes were not associated with anti-proliferative responses to statin treatment. CYP27A1 was heterogeneously expressed among primary tumors, with high expression significantly associated with high tumor grade, ER negativity and basal-like subtype. High CYP27A1 expression was independently prognostic for longer recurrence-free and overall survival. Importantly, the beneficial effect of high CYP27A1 in ER-positive breast cancer seemed limited to women aged ≤50 years. These results establish a link between CYP27A1 and breast cancer pathobiology and prognosis and propose that the efficacy of statins in reducing serum lipids does not directly translate to anti-proliferative effects in tumors. Changes in other undetermined serum or tumor factors suggestively mediate the anti-proliferative effects of statins in breast cancer.


Characterization of the genome of the agent of erythrocyte aplasia permits its classification as a human parvovirus.
It has recently been established that infection with a virus is the most common cause of transient arrest of erythrocyte production in the bone marrow, leading to aplastic crisis, in persons suffering chronic haemolytic anaemias. The physical characteristics of this human virus have suggested that it may be a member of the Parvoviridae. We report here that extraction of nucleic acid from this virus under annealing conditions yielded a single species of double-stranded DNA 5.5 kb in length. Treatment with heat or alkali converted this DNA into a rapidly migrating form sensitive to the single-strand-specific nuclease S1. Extraction of the virion DNA under conditions of low ionic strength where annealing would not be expected to occur yielded DNA which comigrated with the 5.5 kb single-stranded molecule. The results indicate that this virus packages equal numbers of complementary DNA strands into separate virions. It is suggested that this virus can be classified as a member of the genus parvovirus.


[New light on skin photodynamic therapy].
Photodynamic therapy (PDT) relies on the cellular toxicity of an exogenous porphyrin that is activated by light rays. Its specificity depends on its cellular uptake, which is typically high in cells with a high metabolism, such as cancer cells and several microbial pathogens. Both the diffusion of the substrate and the penetration of the light in the tissue limit its efficiency to the first few millimeters of the skin. This explains why this technique is used for the treatment of superficial skin cancers (actinic keratosis and basal cell carcinomas), but also for selected skin inflammatory diseases (psoriasis) or infections (leishmaniosis). However, at the bedside, the limitations of PDT are rather the complexity and the pain associated with the treatment. Herein, we present the new developments, in particular concerning the new light sources, which make PDT a better option for our patients.


Treatment of relapsed acute promyelocytic leukemia by arsenic trioxide in Iran.
Although standard first line treatment of acute promyelocytic leukemia is All trans retinoic acid (ATRA) and chemotherapy, some patients relapse and need a second line of treatment. Relapsed cases of promyelocytic leukemia can be salvaged with arsenic trioxide. Between May 1999 and Jan. 2010, we treated 31 relapsed cases of promyelocytic leukemia with arsenic trioxide. These cases relapsed after previous treatment with ATRA and chemotherapy. We applied arsenic trioxide as 0.15 mg/kg iv infusion until complete remission. After achieving complete remission patients received 2-4 consolidation therapy in the same schedule as remission induction. The median age of patients was 27 years. Complete remission rate was 77.4%. We observed four mortalities during remission induction. With a median follow up of 32 months, ten more relapses occurred. Two year disease-free survival and overall survival for the entire cohort was 54.6% and 81.1%, respectively. Our result is the same as other studies. Thus, we suggest that arsenic trioxide can be used as salvage therapy in patients who relapsed. Despite a good complete remission rate, the relapse rate during the first two years of treatment is high and hematopoietic stem cell transplantation should be considered after achieving complete remission.


Tristetraprolin down-regulates interleukin-8 and vascular endothelial growth factor in malignant glioma cells.
Malignant gliomas are highly aggressive tumors of the central nervous system that rely on production of growth factors for tumor progression. Vascular endothelial growth factor (VEGF), interleukin-8 (IL-8), and tumor necrosis factor-alpha, for example, are up-regulated in these tumors to promote angiogenesis and proliferation. RNA stability, mediated through adenine and uridine-rich elements (ARE) in the 3' untranslated region, is a critical control point for regulating these growth factors. RNA half-life is predominantly governed by a balance between stabilizing and destabilizing factors that bind to ARE. We have previously shown that the stabilizing factor HuR is overexpressed in malignant gliomas and linked to RNA stabilization of angiogenic growth factors. Here, we report that the destabilizing factor tristetraprolin (TTP) is also ubiquitously expressed in primary malignant glioma tissues and cell lines. In contrast to benign astrogliotic tissues, however, the protein was hyperphosphorylated, with evidence implicating the p38/mitogen-activated protein kinase (MAPK) pathway. Conditional overexpression of TTP as a transgene in malignant glioma cells led to RNA destabilization of IL-8 and VEGF and down-regulation of protein production. Analysis of in vivo RNA binding indicated a shift of mRNA toward ectopic TTP and away from endogenous HuR. This biochemical phenotype was associated with a decrease in cell proliferation, loss of cell viability, and apoptosis. We postulate that hyperphosphorylation of TTP via p38/MAPK promotes progression of malignant gliomas by negatively regulating its RNA destabilizing function.


Sedation with propofol during ERCP: is the combination with esketamine more effective and safer than with alfentanil? Study protocol for a randomized controlled trial.
Endoscopic retrograde cholangiopancreatography (ERCP) is a gastrointestinal procedure that requires a relatively motionless patient during the intervention. Deep sedation by intravenous propofol combined with an opioid has recently become the preferred sedation technique. However, when high doses of propofol are used, side effects, namely respiratory depression, may occur. Esketamine has hypnotic, analgesic, and sympathomimetic effects. Our assumption is that a combination of propofol with esketamine reduces the dosage of individual drugs, thereby minimizing sedation side effects while keeping the same satisfaction level of patients and endoscopists. The study will be performed as a randomized controlled multicenter trial. Patients undergoing ERCP, ≥ 18 years old, with American Society of Anesthesiologists (ASA) classification I-III will be randomized after written informed consent to group K (propofol/esketamine) or to group A (propofol/alfentanil). The primary outcome, reflecting effectiveness of sedation, is the total dose of propofol. Secondary outcome parameters are patients' and endoscopists' satisfaction with the procedure and the number of sedation-related pulmonary and cardiovascular events. Data on sedation-related events are collected by recording of oxygen saturation (SpO2), respiratory rate (RR), end-tidal CO2 (etCO2), heart rate (HR), arrhythmias (electrocardiogram (ECG)), and non-invasive blood pressure (NIBP) measurements. Satisfaction parameters are collected by means of questionnaires before and after the procedure and on the following day. Esketamine is known for its effective anesthetic and analgesic effects maintaining spontaneous breathing and airway reflexes. Due to an increase in sympathetic tone, hypotension and cardiac depression is less common. Unfortunately esketamine is also known for its psychotomimetic effects. We aim to demonstrate that the combination of esketamine with propofol for sedation in patients subjected to ERCP interventions is nevertheless superior to a combination of propofol with an opioid. Nederland's Trial Register, NTR5486 . Registered on 17 September 2015.


Laceration repair using a tissue adhesive in a children's emergency department.
To determine the effectiveness of a tissue adhesive, Histoacryl Blue (HAB), for laceration repair in children. Prospective, randomized clinical trial. A tertiary care pediatric emergency center at Egleston Children's Hospital. Children who presented for laceration repair between October 1994 and February 1995 were prospectively evaluated. Patients less than 1 or greater than 18 years of age, those with lacerations greater than 5 cm, and those with lacerations located on the eyelids, ears, nose, lips, hands, feet, joints, or perineum were excluded. Following consent and routine wound management, including subcutaneous closure when deemed necessary, patients were randomized to receive skin sutures or HAB for cutaneous closure. Length of time required for laceration repair was recorded. Parental perception of the pain experienced by their child was assessed using a visual analogue scale. Photographic documentation of scar appearance at the 2-month follow-up visit was evaluated by plastic surgeons using a visual analogue scale. Sixty-one children were enrolled: HAB group (N = 30), suture group (N = 31). No differences occurred between groups in laceration length, depth, location, or patient demographics. Length of time required for repair was decreased (median, HAB 7 minutes vs suture 17.0 minutes) and parental assessment of their child's pain was significantly less in the HAB group. Parents were more likely to recommend HAB over suturing to other parents or guardians. Cosmetic outcome in the HAB group was assessed to be as good as, or better than, the cosmetic outcome in the suture group as evaluated by two plastic surgeons. The use of HAB for laceration repair is an acceptable alternative to conventional suturing with a comparable cosmetic outcome. Advantages include less pain to the child, no need for suture removal, and more efficient use of physician time. Parents were also more likely to recommend HAB over suturing for laceration repair.


Impacts of fertilization systems on nitrogen loss and yield of oilseed rape (Brassica napus L.).
Farmyard manure is considered as a source of plant nutrient supply, but high N loss and low N use efficiency are often serious challenges facing this source of nutrient. It is supposed that a combination of manure with inorganic fertilizers can reduce this problem. A two year experiment was conducted in 2004-2005 at Mazandran province of Iran in order to study the effects of manure, inorganic nitrogen and combination of manure-inorganic nitrogen on N loss and yield of winter oilseed rape (Brassica napus L.) under rainfed conditions. Treatments included 0, 50, 100 and 150 kg N ha(-1) urea (F0, F50, F100, F150), 100 kg N ha(-1) urea + 50 kg N ha(-1) manure (F100M50), 50 kg N ha(-1) urea + 100 kg N ha(-1) manure (F50M100), 150 kg N ha(-1) manure (M150). The highest grain yield (3 ton ha(-1)) was obtained with the 150 kg N ha(-1) as urea treatment in both years. Grain yield in M150 treatment was significantly lower (p < 0.05) than F150. However F100M50 and F50M100 resulted in similar yields compared with F150 treatment. Results also showed that F100M50 and F50M100 treatments decreased N loss (4 and 3 kg N ha(-1) year(-1), respectively) compared to application of manure alone (33.5 kg N ha(-1) year(-1)) and F150 (36 kg N ha(-1) year(-1)). Overall, it could be conducted that F100M50 is the best treatment because it produced similar grain yield compared to F150 while resulted in lower N loss as well.


Association of Physical Activity With Maximal and Submaximal Tests of Exercise Capacity in Middle- and Older-Aged Adults.
Although physical activity (PA) is an important determinant of exercise capacity, the association between these constructs is modest. The authors investigated the associations of self-reported and objectively measured PA with maximal and submaximal tests of exercise capacity. Participants aged ≥40 years (N = 413; 49.6% female) completed a PA questionnaire, wore a uniaxial accelerometer (5.2 ± 1.1 days), and performed maximal (cardiopulmonary exercise test [CPET]) and submaximal (long-distance corridor walk) tests with indirect calorimetry (oxygen consumption, V˙O2). Linear regression models were fitted to assess the variation in exercise capacity explained (partial eta squared, η2) by PA variables. Accelerometer-measured vigorous (η2 = 22% female; η2 = 16% male) and total PA (η2 = 17% female; η2 = 13% male) explained the most variance in CPET V˙O2 (p < .001). All η2 values were lower for long-distance corridor walk V˙O2 (η2 ≤ 11%). Age contributed more to CPET V˙O2 than any PA variable in males (η2 = 32%), but not in females (η2 = 19%). Vigorous and total PA play important roles in CPET V˙O2 in mid to late life.


Phylogenomics reveals extensive reticulate evolution in Xiphophorus fishes.
Hybridization is increasingly being recognized as a widespread process, even between ecologically and behaviorally divergent animal species. Determining phylogenetic relationships in the presence of hybridization remains a major challenge for evolutionary biologists, but advances in sequencing technology and phylogenetic techniques are beginning to address these challenges. Here we reconstruct evolutionary relationships among swordtails and platyfishes (Xiphophorus: Poeciliidae), a group of species characterized by remarkable morphological diversity and behavioral barriers to interspecific mating. Past attempts to reconstruct phylogenetic relationships within Xiphophorus have produced conflicting results. Because many of the 26 species in the genus are interfertile, these conflicts are likely due to hybridization. Using genomic data, we resolve a high-confidence species tree of Xiphophorus that accounts for both incomplete lineage sorting and hybridization. Our results allow us to reexamine a long-standing controversy about the evolution of the sexually selected sword in Xiphophorus, and demonstrate that hybridization has been strikingly widespread in the evolutionary history of this genus.


Two trans-acting eQTLs modulate the penetrance of PRPF31 mutations.
Dominant mutations in the gene encoding the ubiquitously-expressed splicing factor PRPF31 cause retinitis pigmentosa, a form of hereditary retinal degeneration, with reduced penetrance. We and others have previously shown that penetrance is tightly correlated with PRPF31 expression, as lymphoblastoid cell lines (LCLs) from affected patients produce less abundant PRPF31 transcripts than LCLs from their unaffected relatives carrying the same mutation. We have investigated the genetic elements determining the variable expression of PRPF31, and therefore possibly influencing the penetrance of its mutations, by quantifying PRPF31 mRNA levels in LCLs derived from 15 CEPH families (200 individuals), representative of the general population. We found that PRPF31 transcript abundance was a highly variable and highly heritable character. Moreover, by linkage analysis we showed that PRPF31 expression was significantly associated with at least one expression quantitative trait locus (eQTL), spanning a 8.2-Mb region on chromosome 14q21-23. We also investigated a previously mapped penetrance factor located near PRPF31 itself in LCLs from individuals belonging to selected families segregating PRPF31 mutations that displayed reduced penetrance. Our results indicate that, despite its constant association with the non-mutant allele, this factor was able to modulate the expression of both PRPF31 alleles. Furthermore, we showed that LCLs from affected patients have less PRPF31 RNA than those of asymptomatic patients, even at the pre-splicing stage. Altogether, these data demonstrate that PRPF31 mRNA expression and consequently the penetrance of PRPF31 mutations is managed by diffusible compounds encoded by at least two modifiers, acting in a co-regulatory system on both PRPF31 alleles during transcription.


Synthesis of micro and nanostructures in microfluidic systems.
In this critical review, we present an overview of the current progress in synthesis of micro and nanostructures by using microfluidics techniques. Emphasis is placed on processes that can be realized on chip, such as polymerization, precipitation, sol-gel, thermolysis and multistep processes. Continuous flow, microfluidic systems show particular promise in controlling size, shape and size distribution of synthesized micro and nanoparticles. Moreover, the use of microfluidics expands the synthesis space (e.g., temperature, pressure, reagents) to conditions not easily accessed in conventional batch procedures and thus, opens new methods for the realization of complex engineered nanostructures and new materials systems. (187 references).


Cloning and characterisation of the rRNA genes from the human malaria parasite Plasmodium falciparum.
Ribosomal DNA fragments from the human malaria parasite Plasmodium falciparum have been cloned and analysed in detail. Restriction mapping shows that the cloned fragments are different. However, they do have some similarities, in particular a small stretch of A+T-rich DNA located between the small and large subunit rRNA genes. A small rRNA gene has been mapped to this A+T-rich region. Copy number analysis reveals that each fragment is represented approximately 4 times in the genome, and implies that there are a total of 8 rRNA genes organised into at least two classes of transcription unit. Analysis of a third overlapping rDNA fragment indicates that the large subunit rRNA gene of at least one transcription unit contains an intervening sequence.


Self-Equilibration of the Diameter of Ga-Catalyzed GaAs Nanowires.
Designing strategies to reach monodispersity in fabrication of semiconductor nanowire ensembles is essential for numerous applications. When Ga-catalyzed GaAs nanowire arrays are grown by molecular beam epitaxy with help of droplet-engineering, we observe a significant narrowing of the diameter distribution of the final nanowire array with respect to the size distribution of the initial Ga droplets. Considering that the droplet serves as a nonequilibrium reservoir of a group III metal, we develop a model that demonstrates a self-equilibration effect on the droplet size in self-catalyzed III-V nanowires. This effect leads to arrays of nanowires with a high degree of uniformity regardless of the initial conditions, while the stationary diameter can be further finely tuned by varying the spacing of the array pitch on patterned Si substrates.


Do expert assessments converge? An exploratory case study of evaluating and managing a blood supply risk.
Examining professional assessments of a blood product recall/withdrawal and its implications for risk and public health, the paper introduces ideas about perceptions of minimal risk and its management. It also describes the context of publicly funded blood transfusion in Canada and the withdrawal event that is the basis of this study. Interviews with 45 experts from administration, medicine, blood supply, laboratory services and risk assessment took place using a multi-level sampling framework in the aftermath of the recall. These experts either directly dealt with the withdrawal or were involved in the management of the blood supply at the national level. Data from these interviews were coded in NVivo for analysis and interpretation. Analytically, data were interpreted to derive typifications to relate interview responses to risk management heuristics. While all those interviewed agreed on the importance of patient safety, differences in the ways in which the risk was contextualized and explicated were discerned. Risk was seen in terms of patient safety, liability or precaution. These different risk logics are illustrated by selected quotations. Expert assessments did not fully converge and it is possible that these different risk logics and discourses may affect the risk management process more generally, although not necessarily in a negative way. Patient safety is not to be compromised but management of blood risk in publicly funded systems may vary. We suggest ways of managing blood risk using formal and safety case approaches.