Attentional focusing with quantifiers in production and comprehension.
There is a very large number of quantifiers in English, so many that it seems impossible that the only information that they convey is about amounts. Building on the earlier work of Moxey and Sanford (1987), we report three experiments showing that positive and negative quantifiers focus on different subsets of the logical possibilities that quantifiers allow semantically. Experiments 1 and 2 feature a continuation task with quantifiers that span a full range of denotations (from near 0% to near 100%) and show that the effect is not restricted to quantifiers denoting small amounts. This enables a distinction to be made between generalization and complement set focus proper. The focus effects extend to comprehension, as shown by a self-paced reading study (Experiment 3). It is noted that the focus effects obtained are compatible with findings from earlier work by Just and Carpenter (1971), which used a verification paradigm, and in fact these effects constitute a direct test of inferences Just and Carpenter made about mechanisms of encoding negative quantifiers. A related but different explanation is put forward to explain the present data. The experiments show a quantifier function beyond the simple denotation of amount.


Concussion among female middle-school soccer players.
Despite recent increased awareness about sports concussions, little research has evaluated concussions among middle-school athletes. To evaluate the frequency and duration of concussions in female youth soccer players and to determine if concussions result in stopping play and seeking medical care. Prospective cohort study from March 2008 through May 2012 among 4 soccer clubs from the Puget Sound region of Washington State, involving 351 elite female soccer players, aged 11 to 14 years, from 33 randomly selected youth soccer teams. Of the players contacted, 83.1% participated and 92.4% completed the study. Concussion cumulative incidence, incidence rate, and description of the number, type, and duration of symptoms. We inquired weekly about concussion symptoms and, if present, the symptom type and duration, the event resulting in symptom onset, and whether the player sought medical attention or played while symptomatic. Among the 351 soccer players, there were 59 concussions with 43 742 athletic exposure hours. Cumulative concussion incidence was 13.0% per season, and the incidence rate was 1.2 per 1000 athletic exposure hours (95% CI, 0.9-1.6). Symptoms lasted a median of 4.0 days (mean, 9.4 days). Heading the ball accounted for 30.5% of concussions. Players with the following symptoms had a longer recover time than players without these symptoms: light sensitivity (16.0 vs 3.0 days, P = .001), emotional lability (15.0 vs 3.5 days, P = .002), noise sensitivity (12.0 vs 3.0 days, P = .004), memory loss (9.0 vs 4.0 days, P = .04), nausea (9.0 vs 3.0 days, P = .02), and concentration problems (7.0 vs 2.0 days, P = .02). Most players (58.6%) continued to play with symptoms, with almost half (44.1%) seeking medical attention. Concussion rates in young female soccer players are greater than those reported in older age groups, and most of those concussed report playing with symptoms. Heading the ball is a frequent precipitating event. Awareness of recommendations to not play and seek medical attention is lacking for this age group.


The diversity and host interactions of Propionibacterium acnes bacteriophages on human skin.
The viral population, including bacteriophages, is an important component of the human microbiota, yet is poorly understood. We aim to determine whether bacteriophages modulate the composition of the bacterial populations, thus potentially playing a role in health or disease. We investigated the diversity and host interactions of the bacteriophages of Propionibacterium acnes, a major human skin commensal implicated in acne pathogenesis. By sequencing 48 P. acnes phages isolated from acne patients and healthy individuals and by analyzing the P. acnes phage populations in healthy skin metagenomes, we revealed that P. acnes phage populations in the skin microbial community are often dominated by one strain. We also found phage strains shared among both related and unrelated individuals, suggesting that a pool of common phages exists in the human population and that transmission of phages may occur between individuals. To better understand the bacterium-phage interactions in the skin microbiota, we determined the outcomes of 74 genetically defined Propionibacterium strains challenged by 15 sequenced phages. Depending on the Propionibacterium lineage, phage infection can result in lysis, pseudolysogeny, or resistance. In type II P. acnes strains, we found that encoding matching clustered regularly interspaced short palindromic repeat spacers is insufficient to confer phage resistance. Overall, our findings suggest that the prey-predator relationship between bacteria and phages may have a role in modulating the composition of the microbiota. Our study also suggests that the microbiome structure of an individual may be an important factor in the design of phage-based therapy.


Postpartum increase of serum thioredoxin concentrations and the relation to CD8 lymphocytes.
There are few data on oxidative stresses during and after pregnancy, although aggravation of autoimmune disease is implicated in oxidative stress and occurs frequently in the postpartum period. Thioredoxin (TRX) is a stress-inducible protein, and is used as a good biomarker for oxidative stress. To clarify the changes in the levels of oxidative stress during and after pregnancy, we examined serum TRX levels and the numbers of lymphocyte subsets. We measured serum TRX levels by enzyme-linked immunosorbent assay (ELISA), and neutrophils, lymphocytes, and CD4 and CD8 lymphocytes by flow cytometry in peripheral blood from 88 healthy pregnant women, 26 just after delivery women, 77 healthy postpartum women and 19 healthy non-pregnant women. The serum levels of TRX did not change during pregnancy, but increased in four, seven and 10 months postpartum. Serum TRX levels were correlated with the percentages of neutrophils in normal non-pregnant women and women one month postpartum, and with those of CD8 lymphocytes in early pregnant women and women one and four months postpartum. Oxidative stress increased in the postpartum period, and the levels at one and four months postpartum were related to CD8 lymphocytes.


Pharmacokinetic differentiation of drug candidates using system analysis and physiological-based modelling. Comparison of C.E.R.A. and erythropoietin.
Evaluation of the pharmacokinetics (PKs) in a proper physiological context is paramount to elucidate the factors that may improve a drug's PK properties. Using modern system analysis-based physiological modelling principles, this work applies a novel kinetic analysis framework to a PK comparison of two erythropoietically active drugs, C.E.R.A. (continuous erythropoietin receptor activator) and recombinant human erythropoietin (Epo), aimed at elucidating the main factors responsible for the substantial PK differences seen. The evaluation according to the new model is compared with a compartmental model analysis. Sheep (n = 7 for Epo; n = 8 for C.E.R.A.) received intravenous bolus injections of Epo and C.E.R.A. Baseline and 20-30 blood samples per injection were assayed by radioimmunoassay. Fundamental physiologically based PK building block principles were introduced, proceeding to the construction of a general PK model and several sub-models from which a final PK model was selected based on information theoretical principles. The compartmental comparison analysis use a two-compartment model with central Michaelis-Menten elimination. Several lines of evidence support the hypothesis that the desirable slow elimination of C.E.R.A. relative to Epo is mainly caused by a smaller recirculation extraction fraction, which appears more influential on the elimination kinetics than the mean circulation transit time. The compartmental analysis demonstrates large differences in several PK parameters that contribute to C.E.R.A.'s slower elimination, consistent with the recirculation model analysis. It is hypothesized that C.E.R.A.'s smaller recirculatory extraction fraction is due to a reduced receptor-mediated elimination, consistent with in-vitro measurements where C.E.R.A. shows Epo-receptor binding with a lower association constant and a larger dissociation constant.


Contrasting roles of cytochrome P450s in amitraz and chlorfenapyr resistance in the crop pest Tetranychus urticae.
The molecular mechanisms of amitraz and chlorfenapyr resistance remain only poorly understood for major agricultural pests and vectors of human diseases. This study focusses on a multi-resistant field strain of the crop pest Tetranychus urticae, which could be readily selected in the laboratory to high levels of amitraz and chlorfenapyr resistance. Toxicity experiments using tralopyril, the active toxophore of chlorfenapyr, suggested decreased activation as a likely mechanism underlying resistance. Starting from the same parental strain, transcriptome profiling revealed that a cluster of detoxifying genes was upregulated after amitraz selection, but unexpectedly downregulated after chlorfenapyr selection. Further functional validation associated the upregulation of CYP392A16 with amitraz metabolism and the downregulation of CYP392D8 with reduced activation of chlorfenapyr to tralopyril. Genetic mapping (QTL analysis by BSA) was conducted in an attempt to unravel the genetic mechanisms of expression variation and resistance. This revealed that chlorfenapyr resistance was associated with a single QTL, while 3 QTLs were uncovered for amitraz resistance. Together with the observed contrasting gene expression patterns, we argue that transcriptional regulators most likely underly the distinct expression profiles associated with resistance, but these await further functional validation.


Six sigma: process of understanding the control and capability of ranitidine hydrochloride tablet.
The process of understanding the control and capability (PUCC) is an iterative closed loop process for continuous improvement. It covers the DMAIC toolkit in its three phases. PUCC is an iterative approach that rotates between the three pillars of the process of understanding, process control, and process capability, with each iteration resulting in a more capable and robust process. It is rightly said that being at the top is a marathon and not a sprint. The objective of the six sigma study of Ranitidine hydrochloride tablets is to achieve perfection in tablet manufacturing by reviewing the present robust manufacturing process, to find out ways to improve and modify the process, which will yield tablets that are defect-free and will give more customer satisfaction. The application of six sigma led to an improved process capability, due to the improved sigma level of the process from 1.5 to 4, a higher yield, due to reduced variation and reduction of thick tablets, reduction in packing line stoppages, reduction in re-work by 50%, a more standardized process, with smooth flow and change in coating suspension reconstitution level (8%w/w), a huge cost reduction of approximately Rs.90 to 95 lakhs per annum, an improved overall efficiency by 30% approximately, and improved overall quality of the product.


Selection and characterisation of two attenuated vaccine lines of Eimeria tenella in Australia.
To attenuate two strains of Eimeria tenella by selecting for precocious development and evaluate the strains in characterisation trials and by field evaluation, to choose one precocious line for incorporation into an Australian live coccidiosis vaccine for poultry. Two strains from non-commercial flocks were passaged through chickens while selecting for precocious development. Each strain was characterised for drug sensitivity, pathogenicity, protection against homologous and heterologous challenge, and oocyst output in replicated experiments in which the experimental unit was a cage of three birds. Oocyst output and/or body weight gain data collected over a 10 to 12 day period following final inoculation were measured. Feed conversion ratios were also calculated where possible. Fifteen passages resulted in prepatent periods reduced by 24 h for the Redlands strain (from 144 h to 120 h) and 23 h for the Darryl strain (from 139 h to 116 h). Characterisation trials demonstrated that each precocious line was significantly less pathogenic than its parent strain and each effectively induced immunity that protected chickens against challenge with both the parent strain and other virulent field strains. Both lines had oocyst outputs that, although significantly reduced relative to the parent strains, remained sufficiently high for commercial vaccine production, and both showed susceptibility to coccidiostats. Two attenuated lines have been produced that exhibit the appropriate characteristics for use in an Australian live coccidiosis vaccine.


Inferences about the transmission of lumpy skin disease virus between herds from outbreaks in Albania in 2016.
Lumpy skin disease has recently emerged as a major threat to cattle populations outside of Africa, where it is endemic. In 2015 the first ever European outbreaks occurred in Greece, which were followed by spread across much of the Balkans in 2016. Here we use a simple mathematical model for the transmission of lumpy skin disease virus (LSDV) between herds to explore factors influencing its spread by fitting it to data on outbreaks in Albania in 2016. We show that most transmission occurs over short distances (<5 km), but with an appreciable probability of transmission at longer distances. We also show that there is evidence for seasonal variation in the force of infection associated with temperature, possibly through its influence on the relative abundance of the stable fly, Stomoxys calcitrans. These two results together are consistent with LSDV being transmitted by the bites of blood-feeding insects, though further work is required to incriminate specific species as vectors. Finally, we show that vaccination has a significant impact on spread and estimate the vaccine effectiveness to be 76%.


Plasmid- and chromosome-coded aerobactin synthesis in enteric bacteria: insertion sequences flank operon in plasmid-mediated systems.
Large plasmids were detected in two aerobactin-producing enteric bacterial species (Aerobacter aerogenes 62-I, Salmonella arizona SA1, and S. arizona SL5301) and designated pSMN1, pSMN2, and pSMN3, respectively. Other Salmonella spp., namely, S. arizona SL5302, S. arizona SLS, Salmonella austin, and Salmonella memphis, formed aerobactin but contained no detectable large plasmids. S. arizona SL5283 made no aerobactin. A probe consisting of the aerobactin biosynthetic genes cloned on plasmid pABN5 hybridized to a HindIII digest of pSMN1 but not to digests of pSMN2 or pSMN3. A larger probe, the insert of pABN1 containing the complete aerobactin operon, hybridized to four fragments in HindIII digests of the parent plasmid, pColV-K30. A 2.0-kilobase PvuII fragment responsible for this multiple-hybridization pattern was cloned into vector pUC9 to form pSMN30. The latter was mapped and shown to correspond to either IS1 or to a closely related insertion sequence.


En bloc resection for locally advanced cancer of the pancreas: is it worthwhile?
The benefit of radical surgical resection of contiguously involved structures for locally advanced pancreatic cancer is unclear. The aim of this study was to examine patient outcome after extended pancreatic resection for locally advanced tumors and to determine if any subset of extended resection affected outcome. We retrospectively reviewed the records of 116 patients with adenocarcinoma of the pancreas, who underwent extirpative pancreatic surgery between 1987 and 2000. Of the 116 patients, 37 (32%) required resection of surrounding structures (group I), and 79 patients (68%) underwent standard pancreatic resections (group II). In all cases, all macroscopic disease was excised. In group I a total of 46 contiguously involved structures were resected: vascular in 25 patients (54%), mesocolon in 16 (35%) (colic vessels in 3, colon in 13), adrenal in three (7%), liver in one (2%), stomach in one (2%) (for a tumor in the tail of the pancreas), and multiple structures in four. Excision of regional blood vessels included the superior mesenteric vein and/or portal vein in 16, hepatic artery in five, and celiac axis in four. No differences between groups I and II were detected for any of the following parameters: age, sex, history of previous operation, estimated blood loss, or hospital stay. For the entire cohort the morbidity and mortality were 38% and 1.7%, respectively, and these rates were similar in the two groups. Adjuvant therapy was administered to more than 90% of patients in both groups. However, patients in group I were more likely to have received neoadjuvant therapy (76% vs. 42%, P = 0.001). Total pancreatectomy and distal pancreatectomy were more often performed in group I (P = 0.005). Additionally, the median operative time was longer (8.5 hours compared to 6.9 hours (P = 0.0004)). Both groups had similar rates of microscopically positive margins and involved lymph nodes, as well as total number of lymph nodes removed. The median survival was 26 months for patients in group I and 16 months for patients in group II (P = 0.08). The median disease-free survival for groups I and II was 16 months and 14 months, respectively (P = 0.88). In comparing patients in group I, who underwent vascular resection vs. mesocolon (colon or middle colic vessels) resection, the median survival was 26 months and 19 months, respectively (P = 0.12). We were unable to detect a difference in outcome for patients with locally advanced cancers requiring extended pancreatic resections compared to patients with standard resections. En bloc resection of involved surrounding structures, to completely extirpate all macroscopic disease, may be of benefit in selected patients with locally advanced disease, particularly when combined with preoperative chemoradiation therapy.


Motion processing: the most sensitive detectors differ in temporally localized and extended noise.
Contrast thresholds for discriminating orientation and direction of a drifting, oriented grating are usually similar to contrast detection thresholds, which suggest that the most sensitive detectors are labeled for both orientation and direction (Watson and Robson, 1981). This was found to be true in noiseless condition, but Arena et al. (2013) recently found that this was not true in localized noise (i.e., noise having the same spatiotemporal window as the target) as thresholds for discriminating direction were higher than for discriminating orientation. They suggested that this could be explained by the fact that there are more neurons selective to orientation than direction. Another possible interpretation is that, unlike contrast thresholds in absence of noise, the most sensitive detectors in localized noise were labeled for orientation, but not for direction. This hypothesis is supported by recent findings showing different processes operating in localized and extended noise (i.e., full-screen, continuously displayed noise, Allard and Cavanagh, 2011). In the current study, we evaluated contrast thresholds for orientation and direction discrimination tasks in noiseless conditions, and in noise that was either spatially localized or extended, and temporally localized or extended. We found similar orientation and direction thresholds in absence of noise and in temporally extended noise, but greater direction thresholds in temporally localized noise. This suggests that in noiseless and temporally extended noise the most sensitive detectors were labeled for both orientation and direction (e.g., direction-selective complex cells), whereas in temporally localized noise the most sensitive detectors were labeled for orientation but not direction (e.g., simple cells). We conclude that to avoid violating the noise-invariant processing assumption, external noise paradigms investigating motion processing should use noise that is temporally extended, not localized.


Current strategies in reconstruction of maxillectomy defects.
To outline a contemporary review of defect classification and reconstructive options. Review article. Tertiary care referral centers. Although prosthetic rehabilitation remains the standard of care in many institutions, the discomfort of wearing, removing, and cleaning a prosthesis; the inability to retain a prosthesis in large defects; and the frequent need for readjustments often limit the value of this cost-effective and successful method of restoring speech and mastication. However, flap reconstruction offers an option for many, although there is no agreement as to which techniques should be used for optimal reconstruction. Flap reconstruction also involves a longer recovery time with increased risk of surgical complications, has higher costs associated with the procedure, and requires access to a highly experienced surgeon. The surgeon and reconstructive team must make individualized decisions based on the extent of the maxillectomy defect (eg, the resection of the infraorbital rim, the extent of palate excision, skin compromise) and the need for radiation therapy.


Interaction of Protein Isolate with Anthocyanin Extracted from Black Soybean and Its Effect on the Anthocyanin Stability.
The interactions between black soybean protein isolate (B-SPI) and cyanidin 3-O-glucoside (C3G), anthocyanin extracted from black soybean coat was investigated under neutral conditions. The fluorescence spectra showed that C3G had fluorescence quenching effects on B-SPI. Thermodynamic parameters showed that ∆G < 0, which demonstrated that the binding was a spontaneous reaction. Since ΔH > 0 and ΔS > 0, the interactions between C3G and B-SPI was mainly hydrophobic interactions. Fourier infrared spectroscopy results suggested that the contents of α-helix and β-sheet structure showed an increasing trend, whereas the β-angle content displayed a decreasing trend. The degradation of C3G followed first-order kinetics at 85 °C and 100 °C. After the interactions with B-SPI, the degradation rate constant was decreased and the half-life of C3G was prolonged from 70.25 ± 0.90 min to 175.64 ± 38.04 min at 85 °C, from 62.68 ± 1.1 min to 72.51 ± 2.5 min at 100 °C (p < 0.05). The results indicated that the interactions of B-SPI and C3G improved the thermal stability of C3G under heating conditions.


Neoadjuvant chemotherapy for muscle invasive bladder cancer: a nationwide investigation on survival.
Objectives: Randomised controlled trials (RCTs) have investigated the use of neoadjuvant chemotherapy (NAC) and its effect on survival patients with non-metastatic muscle-invasive bladder cancer (MIBC). However, these RCTs have limited external validity and generalisability and, therefore, the current study aims to use real world evidence in the form of observational data to identify the effect that NAC may have on survival, compared to the use of radical cystectomy (RC) alone.Materials and methods: The study cohort (consisting of 944 patients) was selected as a target trial from the Bladder Cancer Data Base Sweden (BladderBaSe). This study calculated 5-year survival and risk of bladder cancer (BC)-specific and overall death by Cox proportional hazard models for the study cohort and a propensity score (PS) matched cohort.Results: Those who had received NAC had higher 5-year survival proportions and decreased risk of both overall and BC specific death (HR = 0.71, 95% CI = 0.52-0.97 and HR = 0.67, 95% CI = 0.48-0.94), respectively, as compared to patients who did not receive NAC. The PS matched cohort showed similar estimates, but with larger statistical uncertainty (Overall death: HR = 0.76, 95% CI = 0.53-1.09 and BC-specific death: HR = 0.73, 95% CI = 0.50-1.07).Conclusion: Results from the current observational study found similar point estimates for 5-year survival and of relative risks as previous studies. However, the results based on real world evidence had larger statistical variability, resulting in a non-statistically significant effect of NAC on survival. Future studies with detailed validated data can be used to further investigate the effect of NAC in narrower patient groups.


Comparison of coronary-artery bypass surgery and stenting for the treatment of multivessel disease.
The recent recognition that coronary-artery stenting has improved the short- and long-term outcomes of patients treated with angioplasty has made it necessary to reevaluate the relative benefits of bypass surgery and percutaneous interventions in patients with multivessel disease. A total of 1205 patients were randomly assigned to undergo stent implantation or bypass surgery when a cardiac surgeon and an interventional cardiologist agreed that the same extent of revascularization could be achieved by either technique. The primary clinical end point was freedom from major adverse cardiac and cerebrovascular events at one year. The costs of hospital resources used were also determined. At one year, there was no significant difference between the two groups in terms of the rates of death, stroke, or myocardial infarction. Among patients who survived without a stroke or a myocardial infarction, 16.8 percent of those in the stenting group underwent a second revascularization, as compared with 3.5 percent of those in the surgery group. The rate of event-free survival at one year was 73.8 percent among the patients who received stents and 87.8 percent among those who underwent bypass surgery (P<0.001 by the log-rank test). The costs for the initial procedure were $4,212 less for patients assigned to stenting than for those assigned to bypass surgery, but this difference was reduced during follow-up because of the increased need for repeated revascularization; after one year, the net difference in favor of stenting was estimated to be $2,973 per patient. As measured one year after the procedure, coronary stenting for multivessel disease is less expensive than bypass surgery and offers the same degree of protection against death, stroke, and myocardial infarction. However, stenting is associated with a greater need for repeated revascularization.


Environmental fate and risk evolution of calcium channel blockers from chlorine-based disinfection to sunlit surface waters.
Organic micropollutants present in disinfected wastewater and discharged to sunlit surface waters may be transformed by multiple processes, such as chlorination due to the presence of chlorine residuals, solar irradiation as well as solar-irradiated chlorine residues. This study reports, for the first time, the multi-scenario degradation kinetics, transformation products, and risk evolution of calcium channel blockers (CCBs), a class of emerging pharmaceutical contaminants with worldwide prevalence in natural waters and wastewater. It was found that the chlorination of the studied CCBs (amlodipine (AML) and verapamil (VER)) was dominated by the reaction of HOCl with their neutral species, with second-order rate constants of 6.15×104 M-1 s-1 (AML) and 7.93×103 M-1 s-1 (VER) at pH 5.0-11.0. Bromination is much faster than chlorination, with the measured kapp,HOBr values of 2.94×105 M-1 s-1 and 6.58×103 M-1 s-1 for AML and VER, respectively, at pH 7.0. Furthermore, both CCBs would undergo photolytic attenuations with hydroxyl and carbonate radicals as the dominant reactive species in water. Notably, free chlorine mainly contributed to their abatement during the solar/chlorine treatment. Additionally, the halogen addition on the aromatic ring was observed during chlorination and bromination of the two CCBs. Cyclization was observed under solar irradiation only, while the aromatic ring was opened in the solar/chlorine system. Some products generated by the three transformation processes exhibited non-negligible risks of high biodegradation recalcitrance and toxicity, potentially threatening the aquatic environment and public health. Overall, this study elucidated the environmental fate of typical CCBs under different transformation processes to better understand the resulting ecological risks in these environmental scenarios.


DIACYLGLYCEROL KINASE 5 regulates polar tip growth of tobacco pollen tubes.
Pollen tubes require a tightly regulated pectin secretion machinery to sustain the cell wall plasticity required for polar tip growth. Involved in this regulation at the apical plasma membrane are proteins and signaling molecules, including phosphoinositides and phosphatidic acid (PA). However, the contribution of diacylglycerol kinases (DGKs) is not clear. We transiently expressed tobacco DGKs in pollen tubes to identify a plasma membrane (PM)-localized isoform, and then to study its effect on pollen tube growth, pectin secretion and lipid signaling. In order to potentially downregulate DGK5 function, we overexpressed an inactive variant. Only one of eight DGKs displayed a confined localization at the apical PM. We could demonstrate its enzymatic activity and that a kinase-dead variant was inactive. Overexpression of either variant led to differential perturbations including misregulation of pectin secretion. One mode of regulation could be that DGK5-formed PA regulates phosphatidylinositol 4-phosphate 5-kinases, as overexpression of the inactive DGK5 variant not only led to a reduction of PA but also of phosphatidylinositol 4,5-bisphosphate levels and suppressed related growth phenotypes. We conclude that DGK5 is an additional player of polar tip growth that regulates pectin secretion probably in a common pathway with PI4P 5-kinases.


Development of passive permeability characteristics of rat placenta during the last third of gestation.
To investigate how the passive permeability of the rat placenta changes during the last third of gestation we measured the unidirectional maternofetal clearance (Kmf) of three polar nonelectrolytes. We found that Kmf (microliters.min-1.g placenta-1) for all three tracers increased between days 15 and 22 (term is 23 days). The increase was less for the largest tracer, [14C]inulin (3.5-fold increase from 0.5 +/- 0.1 to 1.6 +/- 0.1 microliters.min-1.g placenta-1), than for the smaller tracers, [14C]mannitol (7-fold increase from 1.6 +/- 0.1 to 10.9 +/- 0.4 microliters.min-1.g placenta-1) and 51Cr-labeled EDTA (9.5-fold increase from 0.8 +/- 0.04 to 7.6 +/- 0.7 microliters.min-1.g placenta-1). These data suggest that whilst the overall permeability of the rat placenta increases during this period of pregnancy, restriction to the diffusion of large (greater than or equal to 1.5 nm molecular radius) polar nonelectrolytes also increases.


Understanding eating and drinking behaviours in Pakistani university students: A conceptual model through qualitative enquiry.
Excess weight in Pakistan's university students is on the rise and is driven by their maladaptive eating behaviours. Practitioners in Pakistan have adopted Western conceptual models to understand obesogenic eating behaviours. However, these models provide incomplete explanations as they miss important culturally specific determinants for such eating behaviours. The goals of this study were two-fold: first, to explore Pakistani university students' perception of their obesity-related eating behaviours and attitudes; second, to develop a culturally sensitive model of obesogenic eating behaviours in university students from Pakistan. Semi-structured interviews were used with twenty-four Pakistani university students who were categorised as obese using the Body Mass Index according to Asia-Specific cut-offs. Interviews were transcribed, translated, and then analysed through a Grounded Theory methodology. Six major categories emerged from interviews: (1) Obesogenic Eating Habits (Social Eating, Emotional Eating, and Eating Whatever and Whenever You Want); (2) Beliefs about Food in the Culture; (3) Neither Too Fat nor Too Thin body belief (4) Student Life Attitudes; (5) Student Stressors; (6) Inconsistent Weight-Control Strategies. A model was developed with cultural beliefs about food, attitudes towards student-life, and stressors as important determinants of students' obesogenic eating habits, while inconsistent weight-control strategies contributed to further weight gain. The findings highlight the importance of identifying culturally specific determinants of eating behaviours among university students in Pakistan. This emerging model can be used to guide the development of future quantitative and also longitudinal studies aimed at identifying targets for therapeutic interventions to manage obesogenic eating behaviours in Pakistani university students.


Combined wide-field imaging in grading diabetic retinopathy.
To detect retinal neovascularization elsewhere (NVE), of the optic disc (NVD) and intraretinal microvascular abnormalities (IRMA) in treatment naive diabetic retinopathy (DR) and compare these findings by using 90° Wide-Field Colour Fundus Photography (WF CFP), Wide-Field Spectral-Domain Optical Coherence Tomography Angiography (OCTA) and the combination of WF CFP and OCTA through overlay software. Patients with treatment naive severe non-proliferative DR or proliferative DR were prospectively enrolled. All patients underwent WF-CFP and OCTA in the same day. Two readers independently analysed WF-CFP, SD-OCTA and the overlay of the two techniques. The degree of agreement between the two raters and between different techniques (WF CFP, OCTA, WF CFP combined to OCTA) were measured with Cohen's Kappa coefficient. Thirty-one eyes from 21 patients (10 males, mean age 63 ± 15 years) were included. Inter-rater agreement by using WF-CFP in detection of NVE, NVD and IRMA was respectively 0.62, 0.22 and 0.55. OCTA scored values of inter-rater agreement of 0.86, 0.87 and 0.92 in detection of NVE, NVD and IRMA, respectively. By combining WF-CFP and SD-OCTA, inter-rater agreement in detection of NVE, NVD and IRMA was 0.93, 0.94 and 0.89, respectively. Inter-rater agreement in detection of NVE, NVD and IRMA was substantial, fair and moderate, respectively. OCTA provided almost perfect values of inter-rater agreement in NVE, NVD and IRMA detection. Combining WF-CFP and OCTA further empowered concordance values in detection of NVE and NVD. Combining OCTA and WF-CFP is the best performance to detect NVE and NVD.


Cadmium block of squid calcium currents. Macroscopic data and a kinetic model.
The mechanism of Cd2+ block of Ca2+ currents (ICa) was explored in squid neurons using whole-cell patch clamp. Control currents activated sigmoidally, more rapidly at more positive potentials, and did not inactivate significantly. External Cd2+ up to 250 microM reduced ICa reversibly. For small depolarizations, the current for a step of 10 ms increased to a maintained value, resembling the control; but for Vm greater than 0 mV, the increase was followed by a decrease, as Cd2+ block became greater. Final block was greater for larger depolarizations. At 0 mV the half-blocking concentration was 125 microM. Tail currents, measured as channels close, had an initial "hook" when recorded in Cd2+: currents increased transiently, then decreased. This suggests that Cd2+ escapes from some channels, which then conduct briefly before closing. Analysis of tail currents shows that Cd2+ does not slow channel closing. The data can be explained if Cd2+ is a permeant blocker of Ca2+ channels and if channels can close when occupied by Cd2+. Cd2+ permeates the channels, but binds transiently to a site in the pore, obstructing the passage of other ions (e.g., Ca2+). Dwell time depends on the transmembrane potential, becoming shorter for more negative internal potentials. A five-state model was used to simulate the steady-state and kinetic features. It combines a Hodgkin-Huxley type m2 gating scheme and a one-site Woodhull ionic blockage model for a permeant blocker and includes a closed blocked state. To fit the data, the binding site for Cd2+ had to be near the outer end of the pore, with a well depth of -12.2 RT, and with a barrier at each end of the pore. The model predicts that the Cd2+ entry rate is nearly voltage independent, but the exit rate is steeply voltage dependent (e-fold/17 mV). Analysis further suggests that the channel closes at a normal rate with Cd2+ in the pore.


Comparison of non-aureus staphylococcal and mammaliicoccal species found in both composite milk and bulk-tank milk samples of dairy cows collected in tandem.
Non-aureus staphylococci and the closely related mammaliicoccal species (NASM) are the most common causes of bovine subclinical mastitis on modern dairy farms and are highly prevalent in bulk-tank milk. The purpose of this study was to determine the distribution of NASM in both composite cow milk (CCM) and bulk-tank milk (BTM) samples collected in tandem in commercial Flemish dairy herds and to estimate the origin of the different (subgroups of) NASM species present in BTM by applying strain typing (random amplification of polymorphic DNA or random amplified DNA [RAPD]). A single cross-sectional sampling was performed over 5 herds that volunteered to participate in the study. Composite cow milk samples (n = 356) were collected from all lactating cows (except those with clinical mastitis) during a milking in tandem with 6 BTM samples per herd sequentially collected immediately post that milking (n = 30). In total, 421 and 80 NASM isolates were recovered and identified by MALDI-TOF mass spectrometry from the CCM and BTM samples, respectively and a total of 21 and 12 different NASM species were identified from CCM and BTM samples, respectively. Staphylococcus cohnii was the most prevalent NASM species found in BTM followed by Staphylococcus haemolyticus, Staphylococcus epidermidis, Mammaliicoccus lentus, and Staphylococcus equorum, whereas from CCM samples the most common species were S. hemolyticus, S. cohnii, S. equorum, S. epidermidis, and Staphylococcus chromogenes. The prevalent NASM species in both CCM and BTM samples was distinct for each herd, corroborating other studies observing a herd-specific NASM microbiota. Random amplified DNA analysis was performed on 9 NASM species (S. chromogenes, S. epidermidis, S. haemolyticus, S. equorum, Mammaliicoccus sciuri, Staphylococcus xylosus, S. cohnii, Staphylococcus debuckii, and M. lentus) because these species were isolated from both sample types in a herd. The same RAPD types were found in both sample types for all NASM species selected for strain typing in varying degrees. When assessing the distribution of NASM species, differences within NASM species should be examined meaning a closer look should be taken at the strain level rather than at the species level only.


Genes with epigenetic alterations in human pancreatic islets impact mitochondrial function, insulin secretion, and type 2 diabetes.
Epigenetic dysregulation may influence disease progression. Here we explore whether epigenetic alterations in human pancreatic islets impact insulin secretion and type 2 diabetes (T2D). In islets, 5,584 DNA methylation sites exhibit alterations in T2D cases versus controls and are associated with HbA1c in individuals not diagnosed with T2D. T2D-associated methylation changes are found in enhancers and regions bound by β-cell-specific transcription factors and associated with reduced expression of e.g. CABLES1, FOXP1, GABRA2, GLR1A, RHOT1, and TBC1D4. We find RHOT1 (MIRO1) to be a key regulator of insulin secretion in human islets. Rhot1-deficiency in β-cells leads to reduced insulin secretion, ATP/ADP ratio, mitochondrial mass, Ca2+, and respiration. Regulators of mitochondrial dynamics and metabolites, including L-proline, glycine, GABA, and carnitines, are altered in Rhot1-deficient β-cells. Islets from diabetic GK rats present Rhot1-deficiency. Finally, RHOT1methylation in blood is associated with future T2D. Together, individuals with T2D exhibit epigenetic alterations linked to mitochondrial dysfunction in pancreatic islets.


Zoning has little impact on the seasonal diel activity and distribution patterns of wild boar (Sus scrofa) in an UNESCO Biosphere Reserve.
Understanding the spatio-temporal distribution of ungulates is important for effective wildlife management, particularly for economically and ecologically important species such as wild boar (Sus scrofa). Wild boars are generally considered to exhibit substantial behavioral flexibility, but it is unclear how their behavior varies across different conservation management regimes and levels of human pressure. To analyze if and how wild boars adjust their space use or their temporal niche, we surveyed wild boars across the core and buffer zones (collectively referred to as the conservation zone) and the transition zone of a biosphere reserve. These zones represent low and high levels of human pressure, respectively. Specifically, we employed a network of 53 camera traps distributed in the Schaalsee UNESCO Biosphere Reserve over a 14-month period (19,062 trap nights) and estimated circadian activity patterns, diel activity levels, and occupancy of wild boars in both zones. To account for differences in environmental conditions and day length, we estimated these parameters separately for seven 2-month periods. Our results showed that the wild boars were primarily nocturnal, with diurnal activity occurring dominantly during the summer months. The diel activity patterns in the two zones were very similar overall, although the wild boars were slightly less active in the transition zone than in the conservation zone. Diel activity levels also varied seasonally, ranging from 7.5 to 11.0 h day-1, and scaled positively with the length of the night (R 2 = 0.66-0.67). Seasonal occupancy estimates were exceptionally high (point estimates ranged from 0.65 to 0.99) and similar across zones, suggesting that the wild boars used most of the biosphere reserve. Overall, this result suggests that different conservation management regimes (in this case, the zoning of a biosphere reserve) have little impact on wild boar behavior. This finding is relevant for wildlife management in protected areas where possibly high wild boar densities could interfere with conservation goals within these areas and those of agricultural land use in their vicinity.


An innovative educational clinical experience promoting geriatric exercise.
Formal educational training in physical activity promotion is relatively sparse throughout the medical education system. The authors describe an innovative clinical experience in physical activity directed at medical clinicians on a geriatrics rotation. The experience consists of a single 2 1/2 hour session, in which learners are partnered with geriatric patients engaged in a formal supervised exercise program. The learners are guided through an evidence-based exercise regimen tailored to functional status. This experience provides learners with an opportunity to interact with geriatric patients outside the hospital environment to counterbalance the typical geriatric rotation in which geriatric patients are often seen in clinics or hospitals. In this experience, learners are exposed to fit and engaged geriatric patients successfully living in the community despite chronic or disabling conditions. A survey of 105 learners highlighted positive responses to the experience, with 96% of survey respondents indicating that the experience increased their confidence in their ability to serve as advocates for physical activity for older adults, and 89.5% of responders to a follow-up survey indicating that the experience changed their perception of geriatric patients. Modifications to the experience, implemented at partnering facilities are described. The positive feedback from this experience warrants consideration for implementation in other settings.


Mitochondrial temperature homeostasis resists external metabolic stresses.
Based on studies with a fluorescent reporter dye, Mito Thermo Yellow (MTY), and the genetically encoded gTEMP ratiometric fluorescent temperature indicator targeted to mitochondria, the temperature of active mitochondria in four mammalian and one insect cell line was estimated to be up to 15°C above that of the external environment to which the cells were exposed. High mitochondrial temperature was maintained in the face of a variety of metabolic stresses, including substrate starvation or modification, decreased ATP demand due to inhibition of cytosolic protein synthesis, inhibition of the mitochondrial adenine nucleotide transporter and, if an auxiliary pathway for electron transfer was available via the alternative oxidase, even respiratory poisons acting downstream of oxidative phosphorylation (OXPHOS) complex I. We propose that the high temperature of active mitochondria is an inescapable consequence of the biochemistry of OXPHOS and is homeostatically maintained as a primary feature of mitochondrial metabolism.


Sleep Trajectories of Women Undergoing Elective Cesarean Section: Effects on Body Weight and Psychological Well-Being.
After cesarean section (CS), women may be at great risk for sleep disturbance, but little is known about temporal changes in their sleep patterns and characteristics. We had two aims: 1) to identify distinct classes of sleep-disturbance trajectories in women considering elective CS from third-trimester pregnancy to 6 months post-CS and 2) to examine associations of sleep trajectories with body mass index (BMI), depressive symptoms, and fatigue scores. We analyzed data from a prospective cohort study of 139 Taiwanese pregnant women who elected CS. Sleep components were assessed using the Pittsburgh Sleep Quality Index in third-trimester pregnancy, 1 day, 1 week, 1 month, and 6 months post-CS. Data were collected on depressive symptoms, fatigue symptoms, and BMI. Sleep-quality trajectories were identified by group-based trajectory modeling. We identified three distinct trajectories: stable poor sleep (50 women, 36.0%), progressively worse sleep (67 women, 48.2%), and persistently poor sleep (22 women, 15.8%). Poor sleep was significantly associated with pre-pregnancy BMI and more baseline (third-trimester pregnancy) depressive and fatigue symptoms. At 6 months post-CS, women classified as progressively worse or persistently poor sleepers showed a trend toward higher BMI (p<0.03), more depressive symptoms (p<0.001), and higher fatigue scores (p<0.001) than those with stable poor sleep. Women had three distinct sleep-disturbance trajectories before and after elective CS. These poor-sleep courses were associated with BMI and psychological well-being. Our findings suggest a need to continuously assess sleep quality among women considering elective CS and up to 6 months post-CS.


[The role of metabolism disorders in genesis of gallstone disease in children].
Identified changes lipid metabolism in children with biliary disease, characteristic of the metabolic syndrome. The correlation between indices of lipid metabolism with body weight in children with cholelithiasis. However, the degree of impairment of carbohydrate metabolism was independent of body mass index. Obtained data allow us to state that obesity is not always a marker of the metabolic syndrome.


Syntheses and multi-NMR study of fac- and mer-OsO(3)F(2)(NCCH(3)) and the X-ray crystal structure (n = 2) and Raman spectrum (n = 0) of fac-OsO(3)F(2)(NCCH(3)).nCH(3)CN.
Dissolution of the infinite chain polymer, (OsO(3)F(2))(infinity), in CH(3)CN solvent at -40 degrees C followed by solvent removal under vacuum at -40 degrees C yielded fac-OsO(3)F(2)(NCCH(3)).nCH(3)CN (n >/= 2). Continued pumping at -40 degrees C with removal of uncoordinated CH(3)CN yielded fac-OsO(3)F(2)(NCCH(3)). Both fac-OsO(3)F(2)(NCCH(3)).nCH(3)CN and fac-OsO(3)F(2)(NCCH(3)) are yellow-brown solids and were characterized by low-temperature (-150 degrees C) Raman spectroscopy. The crystal structure (-173 degrees C) of fac-OsO(3)F(2)(NCCH(3)).2CH(3)CN consists of two co-crystallized CH(3)CN molecules and a pseudo-octahedral OsO(3)F(2).NCCH(3) molecule in which three oxygen atoms are in a facial arrangement and CH(3)CN is coordinated trans to an oxygen atom in an end-on fashion. The Os---N bond length (2.205(3) A) is among the shortest M---N adduct bonds observed for a d(0) transition metal oxide fluoride. The (19)F NMR spectrum of (OsO(3)F(2))(infinity) in CH(3)CN solvent (-40 degrees C) is a singlet (-99.6 ppm) corresponding to fac-OsO(3)F(2)(NCCH(3)). The (1)H, (15)N, (13)C, and (19)F NMR spectra of (15)N-enriched OsO(3)F(2)(NCCH(3)) were recorded in SO(2)ClF solvent (-84 degrees C). Nitrogen-15 enrichment resulted in splitting of the (19)F resonance of fac-OsO(3)F(2)((15)NCCH(3)) into a doublet ((2)J((15)N-(19)F), 21 Hz). In addition, a doublet of doublets ((2)J((19)F(ax)-(19)F(eq)), 134 Hz; (2)J((15)N-(19)F(eq)), 18 Hz) and a doublet ((2)J((19)F(ax)-(19)F(eq)), 134 Hz) were observed in the (19)F NMR spectrum that have been assigned to mer-OsO(3)F(2)((15)NCCH(3)); however, coupling of (15)N to the axial fluorine-on-osmium environment could not be resolved. The nitrogen atom of CH(3)CN is coordinated trans to a fluorine ligand in the mer-isomer. Quantum-chemical calculations at the SVWN and B3LYP levels of theory were used to calculate the energy-minimized gas-phase geometries, vibrational frequencies of fac- and mer-OsO(3)F(2)(NCCH(3)) and of CH(3)CN. The relative stabilities of the mer- and fac-isomers have been determined and are in accordance with the solution NMR assignments.


A MEDLINE feasibility study.
A MEDLINE feasibility study was conducted with the Northeastern Consortium for Health Information (NECHI) and sponsored by the New England Regional Medical Library Service. It is based on the theory that most potential users and supporters of MEDLINE within hospitals are unaware of its usefulness and applications, and that there exists a need for expanding MEDLINE services to more hospital libraries. The purpose of the study was to provide NECHI with an evaluation of MEDLINE as a feasible service by ascertaining the need and by evaluating the usefulness, satisfaction, and costs of the system. The study demonstrated sufficient use of MEDLINE to justify implementation within NECHI and it provided useful data to determine the future of MEDLINE in each institution. It documented that utilization improved rapidly with publicity and the presence of the system within an institution, that MEDLINE can be an effective and economical complement to the traditional reference services used to support information needs in hospitals, and that more hospital libraries should be able to implement MEDLINE to their advantage once potential users and supporters have been exposed to the system.


Itch sensation through transient receptor potential channels: a systematic review and relevance to manual therapy.
Patients may present with a complaint of "itchiness" or an "odd sensation" that can be relieved by manual therapy treatment options, which demonstrates the relevance of transient receptor potential (TRP) channels. There are studies that identify the role of various TRP channels as modulators of the itch sensation; however, discrepancies in the literature exist with respect to the overall neural pathway of the itch sensation, musculoskeletal implications, and decisive therapeutic implications. The purpose of this study was to review the literature and rate the quality of published articles regarding the role of TRP channels in the itch sensation. A systematic search of relevant literature that was published in English by a peer-reviewed journal between January 2000 and June 2012 was performed in PubMed. Studies that met the predetermined inclusion criteria regarding the relationship between TRP channels and itch were identified and then evaluated for methodological quality by the Downs and Black Quality Index score system and were summarized. Nine studies were identified that met the inclusion criteria, all of which had fair methodological quality from the perspective of the modified Downs and Black Quality Index. TRPA1, TRPM8, and TRPV1-4 were indicated as key channels responsible for the transmission of the itch sensation. TRPV1 channels convey histamine-dependent itch, and TRPA1 channels convey histamine-independent itch. Temperature, nerve growth factor, and substance-P were also described as important itch modulators. There are similarities between the neural pathways responsible for itch, pain, and temperature, which explain the ability of noxious temperature to suppress the desire to scratch. Although transcutaneous electrical nerve stimulation, innocuous vibration, and cutaneous field stimulation have demonstrated relatively weak attenuation of itch, the use of topical capsaicin, noxious heat, and noxious cold have been demonstrated as effective therapies. The findings of this review show that studies have assessed the function of TRP channels and itch, rather than identifying the relationship between itch and effective noninvasive treatment options. Therefore, TRP channels could serve as important, complex clinical targets for manual therapists.


Resolution of genetic and cultural inheritance in twin families by path analysis: application to HDL-cholesterol.
A path model and associated statistical method for the analysis of data on twin families are introduced and applied to high density lipoprotein cholesterol (HDL-c) observations in the Swedish Twin Family Study. The proposed path model incorporates both genetic and environmental sources of familial resemblance, maternal environmental effects, intergenerational differences in heritabilities, marital resemblance due to either primary or secondary phenotypic homogamy, and twin residual environmental correlations. Application of the model to HDL-c levels resulted in parameter estimates consistent with those reported in earlier reviews and in the analysis of nuclear family and twin data. Genetic heritability was estimated as h2 = .363 +/- .243, cultural heritability as c2 = .187 +/- .082, and the proportion of phenotypic variance due to residual environmental effects as r2 = .450 +/- .207. Although the parameter estimates were comparable, the statistical tests of hypotheses were, relative to other designs, of low statistical power. It appears that environmental indices are necessary for powerful tests of hypotheses.


Helical Fasciculation of Bipolar and Horizontal Cell Neurites for Wiring With Photoreceptors in Macaque and Mouse Retinas.
The three-dimensional configurations of rod and cone bipolar cell (BC) dendrites and horizontal cell (HC) processes outside rod and cone synaptic terminals have not been fully elucidated. We reveal how these neurites are mutually arranged to coordinate formation and maintenance of the postsynaptic complex of ribbon synapses in mouse and monkey retinas. Serial section transmission electron microscopy was utilized to reconstruct BC and HC neurites in macaque monkey and mouse, including metabotropic glutamate receptor 6 (mGluR6)-knockout mice. Starting from sporadically distributed branching points, rod BC and HC neurites (B and H, respectively) took specific paths to rod spherules by gradually adjusting their mutual positions, which resulted in a closed alternating pattern of H‒B‒H‒B neurites at the rod spherule aperture. This order corresponded to the array of elements constituting the postsynaptic complex of ribbon synapses. We identified novel helical coils of HC processes surrounding the rod BC dendrite in both mouse and macaque retinas, and these structures occurred more frequently in mGluR6-knockout than wild-type mouse retinas. Horizontal cell processes also formed hook-like protrusions that encircled cone BC and HC neurites below the cone pedicles in the macaque retina. Bipolar and horizontal cell neurites take specific paths to adjust their mutual positions at the rod spherule aperture. Some HC processes are helically coiled around rod BC dendrites or form hook-like protrusions around cone BC dendrites and HC processes. Loss of mGluR6 signaling may be one factor promoting unbalanced neurite growth and compensatory neurite coiling.


Space-bandwidth conditions for efficient phase-shifting digital holographic microscopy.
Microscopy by holographic means is attractive because it permits true three-dimensional (3D) visualization and 3D display of the objects. We investigate the necessary condition on the object size and spatial bandwidth for complete 3D microscopic imaging with phase-shifting digital holography with various common arrangements. The cases for which a Fresnel holographic arrangement is sufficient and those for which object magnification is necessary are defined. Limitations set by digital sensors are analyzed in the Wigner domain. The trade-offs between the various holographic arrangements in terms of conditions on the object size and bandwidth, recording conditions required for complete representation, and complexity are discussed.


Spatial regulation of nanos is required for its function in dendrite morphogenesis.
Spatial control of mRNA translation can generate cellular asymmetries and functional specialization of polarized cells like neurons. A requirement for the translational repressor Nanos (Nos) in the Drosophila larval peripheral nervous system (PNS) implicates translational control in dendrite morphogenesis [1]. Nos was first identified by its requirement in the posterior of the early embryo for abdomen formation [2]. Nos synthesis is targeted to the posterior pole of the oocyte and early embryo through translational repression of unlocalized nos mRNA coupled with translational activation of nos mRNA localized at the posterior pole [3, 4]. Abolishment of nos localization prevents abdominal development, whereas translational derepression of unlocalized nos mRNA suppresses head/thorax development, emphasizing the importance of spatial regulation of nos mRNA [3, 5]. Loss and overexpression of Nos affect dendrite branching complexity in class IV dendritic arborization (da) neurons, suggesting that nos also might be regulated in these larval sensory neurons [1]. Here, we show that localization and translational control of nos mRNA are essential for da neuron morphogenesis. RNA-protein interactions that regulate nos translation in the oocyte and early embryo also regulate nos in the PNS. Live imaging of nos mRNA shows that the cis-acting signal responsible for posterior localization in the oocyte/embryo mediates localization to the processes of class IV da neurons but suggests a different transport mechanism. Targeting of nos mRNA to the processes of da neurons may reflect a local requirement for Nos protein in dendritic translational control.


NeuroVis: Real-Time Neural Information Measurement and Visualization of Embodied Neural Systems.
Understanding the real-time dynamical mechanisms of neural systems remains a significant issue, preventing the development of efficient neural technology and user trust. This is because the mechanisms, involving various neural spatial-temporal ingredients [i.e., neural structure (NS), neural dynamics (ND), neural plasticity (NP), and neural memory (NM)], are too complex to interpret and analyze altogether. While advanced tools have been developed using explainable artificial intelligence (XAI), node-link diagram, topography map, and other visualization techniques, they still fail to monitor and visualize all of these neural ingredients online. Accordingly, we propose here for the first time "NeuroVis," real-time neural spatial-temporal information measurement and visualization, as a method/tool to measure temporal neural activities and their propagation throughout the network. By using this neural information along with the connection strength and plasticity, NeuroVis can visualize the NS, ND, NM, and NP via i) spatial 2D position and connection, ii) temporal color gradient, iii) connection thickness, and iv) temporal luminous intensity and change of connection thickness, respectively. This study presents three use cases of NeuroVis to evaluate its performance: i) function approximation using a modular neural network with recurrent and feedforward topologies together with supervised learning, ii) robot locomotion control and learning using the same modular network with reinforcement learning, and iii) robot locomotion control and adaptation using another larger-scale adaptive modular neural network. The use cases demonstrate how NeuroVis tracks and analyzes all neural ingredients of various (embodied) neural systems in real-time under the robot operating system (ROS) framework. To this end, it will offer the opportunity to better understand embodied dynamic neural information processes, boost efficient neural technology development, and enhance user trust.


Structure, self-cleavage, and replication of two viroid-like satellite RNAs (virusoids) of subterranean clover mottle virus.
Both the genomic and viroid-like satellite RNAs (virusoids) from four subterranean clover mottle virus isolates described by Francki et al. were analyzed in detail. Restriction endonuclease mapping of cDNAs prepared from the genomic RNAs from all isolates showed that these RNAs are closely related if not identical. The two virusoids, which can occur together in the same isolate or individually, were sequenced and shown to be able to form highly base-paired viroid-like secondary structures. The left-hand portions of these structures are almost entirely homologous but the right-hand portions show little similarity. The plus, but not the minus, virusoid RNAs contain sequences that can form the hammerhead self-cleavage structure of certain other self-cleaving viroid, virusoid, and satellite RNAs. Plus, but not minus, RNA transcripts from cDNA clones self-cleaved essentially to completion at the predicted site during transcription in vitro. Northern blot analysis of infected leaf tissue extracts revealed the presence of an oligomeric series of plus RNAs (of monomer size and greater) but minus RNAs were present only as high molecular weight species of heterogeneous size. These findings are in agreement with the lack of minus RNA self-cleavage in vitro. Hence, these virusoid RNAs appear to replicate by a rolling-circle mechanism in which only the plus RNAs self-cleave to form monomeric RNAs.


RNA-based therapeutics in cardiovascular disease.
Cardiovascular disease is the leading cause of death globally, with the number of deaths rising every year. Much effort has gone into development of new treatment strategies. Many RNA species have important regulatory functions in disease initiation and progression, providing interesting new treatment options. This review focuses on different classes of RNA-based therapeutics and provides examples of current clinical and preclinical studies. Current challenges that prevent clinical translation and possibilities to overcome them will be discussed. Different RNA-based molecules have been developed, such as antisense oligos, microRNA mimics and small interfering RNAs. Modifications are used to prevent degradation and immune activation and improve affinity. Additionally, in order to improve delivery of the RNA molecules to the target tissues, viral or nonviral vectors can be used. RNA-based therapy has been shown to be a promising new treatment strategy for different disorders. However, several challenges, such as delivery problems and low efficacy remain. Future research will likely focus on effective delivery to target tissues in order to improve efficacy and avoid harmful side-effects.


Cordyceps militaris fruit body extract ameliorates membranous glomerulonephritis by attenuating oxidative stress and renal inflammation via the NF-κB pathway.
Membranous glomerulonephritis (MGN) is a common pathogenesis of nephritic syndrome in adult patients. Nuclear factor kappa B (NF-κB) serves as the main transcription factor for the inflammatory response mediated nephropathy. Cordyceps militaris, containing various pharmacological components, has been used as a kind of crude drug and folk tonic food for improving immunity and reducing inflammation. The current study aims to investigate the renoprotective activity of Cordyceps militaris aqueous extract (CM) in the cationic bovine serum albumin (C-BSA)-induced rat model of membranous glomerulonephritis. Significant renal dysfunction was observed in MGN rats; comparatively, 4-week CM administration strongly decreased the levels of 24 h urine protein, total cholesterol, triglyceride, blood urea nitrogen and serum creatinine, and increased the levels of serum albumin and total serum protein. Strikingly, recovery of the kidney histological architecture was noted in CM-treated MGN rats. A significant improvement in the glutathione peroxidase and superoxide dismutase levels, and a reduced malondialdehyde concentration were observed in the serum and kidney of CM-treated rats. Altered levels of inflammatory cytokines including interleukins, monocyte chemoattractant protein-1, intercellular adhesion molecule 1, vascular adhesion molecule 1, tumor necrosis factor-α, 6-keto-prostaglandin F1α, and nuclear transcriptional factor subunit NF-κB p65 reverted to normal levels upon treatment with CM. The present data suggest that CM protects rats against membranous glomerulonephritis via the normalization of NF-κB activity, thereby inhibiting oxidative damage and reducing inflammatory cytokine levels, which further provide experimental evidence in support of the clinical use of CM as an effective renoprotective agent.


Spatiotemporal control of miR398 biogenesis, via chromatin remodeling and kinase signaling, ensures proper ovule development.
The coordinated development of sporophytic and gametophytic tissues is essential for proper ovule patterning and fertility. However, the mechanisms regulating their integrated development remain poorly understood. Here, we report that the Swi2/Snf2-Related1 (SWR1) chromatin-remodeling complex acts with the ERECTA receptor kinase-signaling pathway to control female gametophyte and integument growth in Arabidopsis thaliana by inhibiting transcription of the microRNA gene MIR398c in early-stage megagametogenesis. Moreover, pri-miR398c is transcribed in the female gametophyte but is then translocated to and processed in the ovule sporophytic tissues. Together, SWR1 and ERECTA also activate ARGONAUTE10 (AGO10) expression in the chalaza; AGO10 sequesters miR398, thereby ensuring the expression of three AGAMOUS-LIKE (AGL) genes (AGL51, AGL52, and AGL78) in the female gametophyte. In the context of sexual organ morphogenesis, these findings suggest that the spatiotemporal control of miRNA biogenesis, resulting from coordination between chromatin remodeling and cell signaling, is essential for proper ovule development in Arabidopsis.


Anatomical correlates of alien hand syndromes.
The objective of this study was to correlate various alien hand syndromes (AHS) with sites of lesion in 16 patients with anterior cerebral artery (ACA) territory infarction. All previous reports of AHS were case studies. Their clinico-anatomic correlations were still controversial. While the callosal lesion appears necessary for various types of AHS, which portion of the corpus callosum is associated with which syndrome is still not yet completely resolved. Sixteen patients with ACA territory infarction were selected from a stroke registry containing 7355 individuals. They were divided into three lesion groups according to location identified by computed tomography or magnetic resonance imaging: mesial frontal, callosal and combined mesial frontal and callosal. Neurobehavioral examination focused on the presence or absence of grasp reflex, various alien hand signs, intermanual conflict, and callosal disconnection syndrome. By gross visual analysis of the obtained data, a trend for clinicoanatomic correlation emerged. Patients with restricted mesial frontal lesions (three subjects), restricted anterior callosal lesions (four subjects) or "restricted" mesial frontal and anterior callosal lesions (two subjects) did not have symptoms of AHS. The remaining seven patients with extensive callosal injury involving the midbody and isthmus all had symptoms of AHS. Four of the patients with relatively isolated callosal involvement showed intermanual conflict (IMC) associated with a callosal AHS, while the remaining three patients with additional lesions involving the mesial frontal cortex showed impulsive reaching and grasping behaviors of the contralesional hand (a component of frontal AHS) and IMC (a component of callosal AHS). A comparison of the lesions and symptoms of seven patients in two different groups shows that mesial frontal and anterior callosal (genu and rostral body) lesions are associated with a contralateral frontal AHS. Isolated involvement of the callosal midbody and isthmus is associated with a callosal AHS. When the mesial frontal cortex and corpus callosum (genu and whole body) are extensively involved, a mixed frontal and callosal AHS may occur in the same patient.


Long term treatment with luteinising hormone releasing hormone agonists and maintenance of serum testosterone to castration concentrations.
Serum concentrations of luteinising hormone and testosterone were measured by radioimmunoassay one, two, four, seven, and 24 hours after the subcutaneous administration of 500 micrograms of the luteinising hormone releasing hormone agonist [D-Trp6, des-Gly-NH2(10)] LHRH ethylamide or [D-Ser(TBU)6, des-Gly-NH2(10)]LHRH ethylamide in patients who had previously received daily treatment with these peptides for 0, 1, 6, 12, 18, and 24 months. No increase in the serum concentrations of luteinising hormone or testosterone were detected at any time between one and 24 months' treatment. The data show that daily subcutaneous administration of the two luteinising hormone releasing hormone agonists used at the appropriate dose can maintain concentrations of serum androgens equivalent to those after castration during long term treatment.


Translocation of antibiotic resistance determinants including an extended-spectrum beta-lactamase between conjugative plasmids of Klebsiella pneumoniae and Escherichia coli.
The extended-spectrum beta-lactamase CAZ-7, derived from TEMs, was produced by two different strains of the family Enterobacteriaceae, Klebsiella pneumoniae and Escherichia coli, isolated from the same patient. Both isolates were resistant to amikacin. In addition, the K. pneumoniae strain was TEM-1 producing and resistant to gentamicin. An E. coli HB101 transconjugant obtained from K. pneumoniae, selected on ceftazidime, showed that CAZ-7 and amikacin resistance were encoded by an 85-kb Inc7 or M plasmid, while an E. coli HB101 transconjugant obtained from E. coli under the same conditions showed that CAZ-7 and amikacin resistance were encoded by a greater than 150-kb Inc6 or C plasmid. Two other E. coli HB101 transconjugants obtained from K. pneumoniae, selected on gentamicin or chloramphenicol, showed that TEM-1 and gentamicin resistance could be encoded either by a greater than 150-kb Inc6 or C plasmid or by an 85-kb Inc7 or M plasmid. It was hypothesized that the genes for beta-lactam and aminoglycoside resistances were located on translocatable sequences. EcoRI digestion and hybridizations obtained with blatem, aacA4, and IS15 probes demonstrated that the CAZ-7 gene, amikacin resistance gene, and IS15 element were clustered on an approximately 20-kb fragment common to 85- and greater than 150-kb plasmids. E. coli HB101 transconjugants from K. pneumoniae and E. coli isolates were used to obtain translocations of CAZ-7 and amikacin resistance and of TEM-1 and gentamicin resistance between the 85- and greater than 150-kb plasmids. This study shows a typical example of in vivo gene dissemination involving transposable elements which translocate multiresistance genes, including an extended-spectrum beta-lactamase.


Uncommon somatic mutations in metastatic NUT midline carcinoma.
NUT midline carcinoma (NMC) is a rare and aggressive epithelial cancer arising from median organs. It is driven by chromosomal translocation t(15;19) involving the rearrangement of NUT (nuclear protein in testis) and BRD4 (bromodomain 4) genes leading to fusion oncoprotein BRD4-NUT. We report the case of a woman who was previously treated with induction chemotherapy, surgery, radiotherapy and adjuvant trastuzumab for HER-2 positive invasive ductal carcinoma of the breast. After 6 months of follow-up a lung nodule appeared. A biopsy showed an adenocarcinoma fetal type/lung blastoma, so a left inferior lobectomy was performed: NMC harboring BRD4-NUT rearrangement was diagnosed. After 9 months of follow-up, bone and soft tissue metastases occurred, so the patient was given radiotherapy. Next-generation sequencing technology identified somatic mutations in deleted in colorectal cancer (DCC), mixed lineage leukemia protein 3 (MLL3), and splicing factor 3B subunit 1 (SF3B1) genes in NMC cells from both primitive cancer and metastases. The patient was treated with the experimental BRD4 inhibitor for 10 months, until the disease progressed to the lung and bone. After spinal cord compression, the patient was offered palliative radiotherapy to bone and eventually died aged 39 years. To the best of our knowledge, our case is the first DCC, MLL3, and SF3B1 mutated NUT midline carcinoma reported in the literature. If these mutations were confirmed to play a role in this neoplasm, clinical trials analyzing targeted therapies should be considered, eg. colorectal cancer-like chemotherapies for DCC mutations, hypomethylating agents for MLL3 mutations or SF3B1 inhibitors in case of specific somatic mutations.


De novo designed lipopolysaccharide binding peptides: structure based development of antiendotoxic and antimicrobial drugs.
Lipopolysaccharide (LPS), the glycolipid of the outer membrane of Gram-negative bacteria, is critically involved in health and diseases. LPS facilitates the survival of pathogens by imposing a permeability barrier against antibiotics and antimicrobial peptides. LPS, also termed as endotoxin, functions as a potent inducer of innate immunity. Interception of endotoxin in systemic circulation by immune cells e.g. macrophages is essential to mount surveillance against invading microbes. However, a hyper-activated immune response may lead to the overwhelming production of tissue damaging cytokines TNF-α, IL-1, IL-6 and free radicals that may cause multiple organ failures or septic shock syndromes. The sepsis or septic shock is the major cause of mortality; 120,000 deaths/year occur in the United States alone, in the intensive care units. To-date, no therapeutic is available to combat sepsis mediated lethality. Furthermore, bacterial resistance against commonly used antibiotics has been increasing at an alarming rate necessitating a search for antibacterial agents with novel mode of actions. LPS could be a valid drug target for the development of antiendotoxic and antimicrobial compounds. In this article, recent advances in structural basis of LPS recognition by its receptor proteins and mode of actions of antimicrobial peptides defensins and cathelicidins are reviewed. Our research has identified, through de novo design, antimicrobial and endotoxin interacting β-boomerang peptides. Structure-activity correlations (SAR) of these peptides have been discussed, highlighting future design to achieve potent LPS neutralizing molecules.


Health surveillance and response on a regional scale: a preliminary study of the Zika virus fever case.
Although awareness of the Zika virus has existed since the 1950s, only recently has it attracted the interest of the international community. In 2015 and 2016, the virus spread throughout Brazil and suspicions on the possible relation between parallel increases in neurological disorders and the infection arose. By November 2015, this concern had developed into a National Public Health Emergency. On February 1, 2016, WHO formally declared its suspicion that this was a Public Health Emergency of International Concern (PHEIC), and sent a response in accordance with International Health Regulations (2005). Zika is present in almost all South American countries, and PAHO/WHO, Unasur, and Mercosur are developing responsive actions to the epidemic. The aim of this article is to present a critical analysis of the regional South American and Brazilian responses of February through September 2016, in respect of this PHEIC announcement, utilizing qualitative methodologies via bibliographical examination and document analysis. In this context, the PAHO/WHO played a prominent role as compared with the other organizations. Moreover, the political environment of the region also played a major role in the instability of both Mercosur and Unasur, which could impact the capacity and effectiveness of the response.


Magnetically Targeted Nanocapsules for PAA-Cisplatin-Conjugated Cores in PVA/SPIO Shells via Surfactant-Free Emulsion for Reduced Nephrotoxicity and Enhanced Lung Cancer Therapy.
Cis-diamminedichloroplatinum (II) (cisplatin, CDDP) is one of the most potent chemotherapy agents, but its side effects toward normal tissues, particularly toxicity in the kidney and nonspecific biodistribution, limit its ability to have significant clinical activity against a variety of solid tumors. A magnetic CDDP-encapsulated nanocapsule (CDDP-PAA-NC) with CDDP-polyacrylic acid (PAA) core in amphiphilic polyvinyl alcohol/superparamagnetic iron oxide nanoparticles shell is synthesized through a double emulsion to provide both high loading efficiency and controlled drug release. The CDDP-PAA-NCs significantly increase the blood circulation time of CDDP in vivo, with nearly 100-fold higher concentration, and drastically reduce side effects, including nephrotoxicity and hepatotoxicity, compared with the delivery of free CDDP. Furthermore, with a magnetic targeting effect, the CDDP-PAA-NCs show ninefold higher level accumulation in tumor tissue than the free CDDP treatment when administered at the equivalent dose, and mice treated with the CDDP-PAA-NCs display approximately 3.5-fold lower tumor volume than those of the control group on day 24. This result demonstrates that the magnetic CDDP-PAA-NCs, which are synthesized using a facile emulsion process, can significantly reduce toxicity and exhibit anticancer activity in A549-tumor bearing mice with negligible side effects.


Skin autofluorescence: an emerging biomarker in persons with kidney disease.
Skin autofluorescence (SAF) is a measure of the accumulation of advanced glycation end-products (AGEs) proposed to act as a marker of 'cumulative metabolic stress'. This article discusses mechanisms of AGE formation and reviews published literature on SAF as a biomarker and risk factor across the spectrum of kidney disease. SAF is elevated in adults and children on dialysis. Higher SAF is an independent risk factor for cardiovascular and all-cause mortality in persons receiving haemodialysis and for all-cause mortality in persons performing peritoneal dialysis, though the increase in discrimination when SAF was added to traditional risk factors was modest. In less advanced chronic kidney disease, higher SAF predicts all-cause mortality and progression. SAF is elevated in renal transplant recipients, but to a lesser extent than in dialysis patients. In one study, higher SAF predicted graft loss and mortality. SAF has been reported to be increased in patients with acute kidney injury. A growing body of evidence attests that SAF, a marker of AGE accumulation, is a risk factor for mortality and kidney function decline in multiple types of kidney disease. Further studies are warranted to evaluate interventions to reduce SAF and the impact on clinical outcomes.


[Determination of morphotypes of Candida spp. in vaginal smears].
Samples of vaginal smears were taken from 100 patients suspected of vaginal candidiasis that attended the Microbiology Laboratory of "Freyre de Andrade" Clinical and Surgical Hospital, in Havana City. These samples were cultivated in Sabouraud agar and Sabouraud triphenyltetrazolium agar (STA). In 45 % of the samples it was observed growth of the yeast-shaped colonies, where Candida albicans (51.1 %) and C. glabrata (22.2 %) were the most frequently isolated species. It was proved that STA allowed to differentiate the morphotypes of the yeast species and it was observed that most of the species presented more than one morphotype with the predominance of flat light pink colonies without mycelial halo in C. albicans, C. glabrata did not grow in it. This phenotypic typing in STA will permit to approach epidemiological studies in a future.


Machine learning prediction model of acute kidney injury after percutaneous coronary intervention.
Acute kidney injury (AKI) after percutaneous coronary intervention (PCI) is associated with a significant risk of morbidity and mortality. The traditional risk model provided by the National Cardiovascular Data Registry (NCDR) is useful for predicting the preprocedural risk of AKI, although the scoring system requires a number of clinical contents. We sought to examine whether machine learning (ML) techniques could predict AKI with fewer NCDR-AKI risk model variables within a comparable PCI database in Japan. We evaluated 19,222 consecutive patients undergoing PCI between 2008 and 2019 in a Japanese multicenter registry. AKI was defined as an absolute or a relative increase in serum creatinine of 0.3 mg/dL or 50%. The data were split into training (N = 16,644; 2008-2017) and testing datasets (N = 2578; 2017-2019). The area under the curve (AUC) was calculated using the light gradient boosting model (GBM) with selected variables by Lasso and SHapley Additive exPlanations (SHAP) methods among 12 traditional variables, excluding the use of an intra-aortic balloon pump, since its use was considered operator-dependent. The incidence of AKI was 9.4% in the cohort. Lasso and SHAP methods demonstrated that seven variables (age, eGFR, preprocedural hemoglobin, ST-elevation myocardial infarction, non-ST-elevation myocardial infarction/unstable angina, heart failure symptoms, and cardiogenic shock) were pertinent. AUC calculated by the light GBM with seven variables had a performance similar to that of the conventional logistic regression prediction model that included 12 variables (light GBM, AUC [training/testing datasets]: 0.779/0.772; logistic regression, AUC [training/testing datasets]: 0.797/0.755). The AKI risk model after PCI using ML enabled adequate risk quantification with fewer variables. ML techniques may aid in enhancing the international use of validated risk models.


The electrophoresis of histones in polyacrylamide gel and their quantitative determination.
1. A new method has been devised for the separation of the histone fractions of calf thymus by electrophoresis in polyacrylamide gel at pH2.4. 2. The fractions have been characterized by their relative mobilities with respect to a marker protein, bovine plasma albumin. 3. A method has been developed for the quantitative determination of the separated histone fractions by measuring the colour yields of dye-histone complexes formed in the gel.


Simple shifts in the voltage dependence of sodium channel gating caused by divalent cations.
The effect of elevated divalent cation concentration on the kinetics of sodium ionic and gating currents was studied in voltage-clamped frog skeletal muscle fibers. Raising the Ca concentration from 2 to 40 mM resulted in nearly identical 30-mV shifts in the time courses of activation, inactivation, tail current decay, and ON and OFF gating currents, and in the steady state levels of inactivation, charge immobilization, and charge vs. voltage. Adding 38 mM Mg to the 2 mM Ca bathing a fiber produced a smaller shift of approximately 20 mV in gating current kinetics and the charge vs. voltage relationship. The results with both Ca and Mg are consistent with the hypothesis that elevated concentrations of these alkali earth cations alter Na channel gating by changing the membrane surface potential. The different shifts produced by Ca and Mg are consistent with the hypothesis that the two ions bind to fixed membrane surface charges with different affinities, in addition to possible screening.


[Hospital drug supply around the turn of the century--the founding of the pharmacy at the city hospital of Worms].
Around the turn of the century drug supply of the civil hospital in Worms was carried out by local pharmacists, drug distribution and preparation of simple solutions by a nurse. The municipal authorities which were responsible for the hospital were sure that the establishment of a pharmacy in the hospital itself could improve drug supply. The study shows how the authorities went through with the opening of a hospital pharmacy despite the expected opposition of the local pharmacists and that such an establishment and the employment of a pharmacist were profitable even for a hospital with only 200 beds.


Why it is so hard to detect Luttinger liquids in angle resolved photo-emission spectroscopy?
The problem of photoemission from a quasi-1D material is studied. We identify two issues that play a key role in the detection of gapless Tomonaga-Luttinger liquid (TLL) phase. Firstly, we show how a disorder-backward scattering as well as forward scattering component-is able to significantly obscure the TLL states, hence the initial state of angle resolved photo-emission spectroscopy (ARPES). Secondly, we investigate the photo-electron propagation towards a sample's surface. We focus on the scattering path operator contribution to the final state of ARPES. We show that, in the particular conditions set by the 1D states, one can derive an exact analytical solution for this intermediate stage of ARPES. The solution shows that for particular energies of incoming photons the intensity of photo-current may be substantially reduced. Finally, we put together the two aspects (the disorder and the scattering path operator) to show the full, disruptive force of any inhomogeneities on the ARPES amplitude.


Correlation of respirator fit measured on human subjects and a static advanced headform.
This study assessed the correlation of N95 filtering facepiece respirator (FFR) fit between a Static Advanced Headform (StAH) and 10 human test subjects. Quantitative fit evaluations were performed on test subjects who made three visits to the laboratory. On each visit, one fit evaluation was performed on eight different FFRs of various model/size variations. Additionally, subject breathing patterns were recorded. Each fit evaluation comprised three two-minute exercises: "Normal Breathing," "Deep Breathing," and again "Normal Breathing." The overall test fit factors (FF) for human tests were recorded. The same respirator samples were later mounted on the StAH and the overall test manikin fit factors (MFF) were assessed utilizing the recorded human breathing patterns. Linear regression was performed on the mean log10-transformed FF and MFF values to assess the relationship between the values obtained from humans and the StAH. This is the first study to report a positive correlation of respirator fit between a headform and test subjects. The linear regression by respirator resulted in R(2) = 0.95, indicating a strong linear correlation between FF and MFF. For all respirators the geometric mean (GM) FF values were consistently higher than those of the GM MFF. For 50% of respirators, GM FF and GM MFF values were significantly different between humans and the StAH. For data grouped by subject/respirator combinations, the linear regression resulted in R(2) = 0.49. A weaker correlation (R(2) = 0.11) was found using only data paired by subject/respirator combination where both the test subject and StAH had passed a real-time leak check before performing the fit evaluation. For six respirators, the difference in passing rates between the StAH and humans was < 20%, while two respirators showed a difference of 29% and 43%. For data by test subject, GM FF and GM MFF values were significantly different for 40% of the subjects. Overall, the advanced headform system has potential for assessing fit for some N95 FFR model/sizes.


Blood Pressure Effect of Traffic-Related Air Pollution : A Crossover Trial of In-Vehicle Filtration.
Ambient air pollution, including traffic-related air pollution (TRAP), increases cardiovascular disease risk, possibly through vascular alterations. Limited information exists about in-vehicle TRAP exposure and vascular changes. To determine via particle filtration the effect of on-roadway TRAP exposure on blood pressure and retinal vasculature. Randomized crossover trial. (ClinicalTrials.gov: NCT05454930). In-vehicle scripted commutes driven through traffic in Seattle, Washington, during 2014 to 2016. Normotensive persons aged 22 to 45 years (n = 16). On 2 days, on-road air was entrained into the vehicle. On another day, the vehicle was equipped with high-efficiency particulate air (HEPA) filtration. Participants were blinded to the exposure and were randomly assigned to the sequence. Fourteen 3-minute periods of blood pressure were recorded before, during, and up to 24 hours after a drive. Image-based central retinal arteriolar equivalents (CRAEs) were measured before and after. Brachial artery diameter and gene expression were also measured and will be reported separately. Mean age was 29.7 years, predrive systolic blood pressure was 122.7 mm Hg, predrive diastolic blood pressure was 70.8 mm Hg, and drive duration was 122.3 minutes (IQR, 4 minutes). Filtration reduced particle count by 86%. Among persons with complete data (n = 13), at 1 hour, mean diastolic blood pressure, adjusted for predrive levels, order, and carryover, was 4.7 mm Hg higher (95% CI, 0.9 to 8.4 mm Hg) for unfiltered drives compared with filtered drives, and mean adjusted systolic blood pressure was 4.5 mm Hg higher (CI, -1.2 to 10.2 mm Hg). At 24 hours, adjusted mean diastolic blood pressure (unfiltered) was 3.8 mm Hg higher (CI, 0.02 to 7.5 mm Hg) and adjusted mean systolic blood pressure was 1.1 mm Hg higher (CI, -4.6 to 6.8 mm Hg). Adjusted mean CRAE (unfiltered) was 2.7 μm wider (CI, -1.5 to 6.8 μm). Imprecise estimates due to small sample size; seasonal imbalance by exposure order. Filtration of TRAP may mitigate its adverse effects on blood pressure rapidly and at 24 hours. Validation is required in larger samples and different settings. U.S. Environmental Protection Agency and National Institutes of Health.


[Reptiles from Cerro Colorado and its surroundings, Cumana, Sucre State, Venezuela].
An inventory of the reptiles that inhabit in Cerro Colorado and its surroundings, was performed from March, 1994 to March, 1995. There were reported 8 species of snakes and 7 of lizards enclosed in 4 and 5 families repectively. Aspects observed were ecolology as habitat, activity, reproduction and relative abundance. The more abundant species of lizards were: Cnemidophorus femniscatus, Ameiva bifrontata, (Teiidae), Tropidurus hispidus (Tropiduridae), Gonatodes vittatus and Hemidactylus mabouia (Gekkonidae) and the ophidians: Leptodeira annulata and Mastigodryas amarali (Colubridae). It is believed that the changes occurred in the zone influenced the increase of the relative abundance of the species Leptotyphlops goudotii (Leptotyphlopidae) arid Gymnophthalmus speciosus(Gymnophthalmidae) and perhaps in the disappearance of others that have been reported at the xerophitic or semixerophitic zones of the Sucre State of Venezuela.


Ordering the cell death pathway. Differential effects of BCL2, an interleukin-1-converting enzyme family protease inhibitor, and other survival agents on JNK activation in serum/nerve growth factor-deprived PC12 cells.
Previous studies indicate that activation of c-Jun kinase (JNK) is necessary for apoptosis of trophic factor-deprived PC12 cells and that death in this system is suppressed by multiple agents, including BCL2, inhibitors of the interleukin-1-converting enzyme (ICE) family of proteases, blockers of transcription, and a variety of small molecules with differing modes of action. Here, we determine the order in which these agents block apoptosis relative to JNK activation. Overexpression of BCL2 promotes PC12 cell survival and blocks JNK activation caused by trophic factor withdrawal. Similarly, the survival-promoting agents aurintricarboxylic acid, N-acetylcysteine, the nitric oxide generator diethylenetriamine nitric oxide, 8-bromo-cGMP, and 8-(4-chlorophenylthio)-cAMP act upstream to inhibit JNK activation. In contrast, zVAD-fluoromethylketone (a permeant ICE family inhibitor), actinomycin D, and the G1/S cell cycle inhibitor deferoxamine, all promote survival after trophic factor withdrawal, but do not affect JNK activation. These findings are consistent with the presence of an ordered cell death pathway triggered by trophic factor deprivation in which 1) BCL2 and a number of survival-promoting agents act upstream of JNK, 2) ICE family protease actions, regulated genes required for cell death, and certain cell cycle blockers lie either downstream of JNK or on independent pathways required for apoptotic death.


Sex-related differences in the effects of late winter pairing activity and seasonal influences on neuroendocrinology and gonadal development of mallards.
The importance of late winter pairing activity on the neuroendocrinology of wild waterfowl is unknown. In this study, we examined the sex-related differences in the roles of late winter pairing activity and seasonal influences on neuroendocrine and reproductive physiology in both male and female mallards. Our main goals were to determine (1) which physiological responses were influenced by pairing status or by seasonal changes and (2) whether responses differed between the sexes. Thus, physiological responses of mallards in different pairing status categories were assessed at two times: January 28 to February 5 and February 24 to March 3. Ducks were assigned to one of the following pairing status categories: strong pairs, temporary pairs, unpaired or lone birds within the flock, or birds isolated in same-sex groups. Seasonal changes correlated with increases in both gonadal mass and hypothalamic content of vasoactive intestinal peptide in both sexes, whereas only pairing status correlated with changes in body mass in both sexes. The main sex-related differences were the following: (1) Seasonal decreases in hypothalamic gonadotrophin releasing hormone II content occurred only in females. (2) Seasonal increases in serum prolactin occurred only in males, whereas levels in females were low throughout the study. (3) Both male and female gonadal masses increased seasonally, but male gonadal mass was initially twice that of females. (4) Body mass of both sexes was influenced by pairing status correlations (i.e., all paired or lone birds were heavier than isolated birds), but body mass in males decreased seasonally. No sex-related differences occurred in hypothalamic gonadotrophin releasing hormone I content or circulating serum luteinizing hormone. Taken together, these results indicate that seasonal reproduction in mallards is regulated not only by seasonal but also by social cues, and differences occur between the sexes, months in advance of actual breeding.


LeishIF4E2 is a cap-binding protein that plays a role in Leishmania cell cycle progression.
Leishmania encode six paralogs of the cap-binding protein eIF4E and five eIF4G candidates, forming unique complexes. Two cap-binding proteins, LeishIF4E1 and LeishIF4E2, do not bind any identified LeishIF4Gs, thus their roles are intriguing. Here, we combine structural prediction, proteomic analysis, and interaction assays to shed light on LeishIF4E2 function. A nonconserved C-terminal extension was identified through structure prediction and sequence alignment. m7 GTP-binding assays involving both recombinant and transgenic LeishIF4E2 with and without the C-terminal extension revealed that this extension functions as a regulatory gate, modulating the cap-binding activity of LeishIF4E2. The interactomes of the two LeishIF4E2 versions were investigated, highlighting the role of the C-terminal extension in binding to SLBP2. SLBP2 is known to interact with a stem-loop structure in the 3' UTRs of histone mRNAs. Consistent with the predicted inhibitory effect of SLBP2 on histone expression in Xenopus laevis, a hemizygous deletion mutant of LeishIF4E2, exhibited an upregulation of several histones. We therefore propose that LeishIF4E2 is involved in histone expression, possibly through its interaction between SLBP2 and LeishIF4E2, thus affecting cell cycle progression. In addition, cell synchronization showed that LeishIF4E2 expression decreased during the S-phase, when histones are known to be synthesized. Previous studies in T. brucei also highlighted an association between TbEIF4E2 and SLBP2, and further reported on an interaction between TbIF4E2 and S-phase-abundant mRNAs. Our results show that overexpression of LeishIF4E2 correlates with upregulation of cell cycle and chromosome maintenance proteins. Along with its effect on histone expression, we propose that LeishIF4E2 is involved in cell cycle progression.


Recrudescence of severe polyneuropathy after receiving Pfizer-BioNTech COVID-19 vaccine in a patient with a history of eosinophilic granulomatosis with polyangiitis.
A middle age man with a history of diabetes mellitus type 2, hypertension, migraine and eosinophilic granulomatosis with polyangiitis (EGPA) with polyneuropathy in remission presented with paresthesia and motor weakness soon after receiving the Pfizer-BioNTech COVID-19 messanger RNA (mRNA) vaccine. The patient had polyneuropathy 10 years ago secondary to EGPA, which had resolved. EGPA was diagnosed on the basis of typical symptoms and positive sural nerve biopsy. Five days after receiving the first dose of COVID-19 vaccine, he developed heaviness and reduced dexterity of both the upper extremities, which progressed to patchy and asymmetric motor weakness of all four extremities. Given the lack of clear alternative explanation after a thorough work up, recrudescence of underlying asymptomatic polyneuropathy due to a possible reaction to COVID-19 mRNA vaccine was considered although a temporal association with vaccine dose does not prove causality. He was treated with corticosteroids with slow improvement of his symptoms.


New approaches for epidemiologic studies of mortality statistics.
Finding and analyzing multiple causes of death-rather than single causes-has major epidemiologic advantages. Besides helping to reveal the magnitude of the causes or morbid conditions leading to death, it also demonstrates that deaths are usually the result of several simultaneous or sequential causes. This article reviews ways that multiple cause of death data have been analyzed in order to improve our knowledge of these causes and other relevant health factors.