Myocardial scintigraphy--25 years after start.
The development of myocardial scintigraphy (MS) reflects the clinical success of a representative procedure in nuclear medicine. Radiopharmaceuticals for visualizing vital and damaged myocardium and techniques (planar-qualitative, planar-quantitative, SPECT-qualitative-quantitative with comparative sensitivities) are briefly reviewed with the main focus on their clinical application in coronary (CHD) and noncoronary heart disease, where recent literature from the United States and Europe is considered. The limited value of MS for screening of CHD is outlined and its present and future role in detecting asymptomatic (silent) ischemia/infarction and symptomatic patients at professional risk is stressed. The present state of MS in coronary heart disease is discussed for single and multivessel disease, previous infarction, and risk stratification (myocardial washout, pulmonary uptake, ischemic dilation, absent heart sign), reflecting the importance of the procedure in exercise-induced ischemia as well as in ischemia at rest for prognostication of the natural and therapeutic course, i.e., therapy control (angioplasty, bypass, lysis, cardiac drugs). More marginal but upcoming clinical indications are mentioned, such as progressive systemic sclerosis, cardiac transplantation, pediatric cardiology, and problems of nephrology/urology. The "normal" values and the impact of digital radiology and of contrast cardiography are touched upon. Preliminary cases with 111In-antimyosin and 99mTc-Isonitriles are presented including correlative results between global ejection fraction determination according to gated 99mTc-isonitrile and conventional 99mTc-erythrocyte ventriculogram (r = 0.75; n = 10).


Solubilisation of [60]fullerenes using block copolymers and evaluation of their photodynamic activities.
Unmodified [60]fullerenes (C60) were solubilised with high stability using various type of poly(ethylene glycol) (PEG) based block copolymer micelles. Block copolymer micelle-incorporated C60 fullerenes were studied in cultures for biological activities using human cervical cancer HeLa cells. As a result, the cationic block copolymer micelles delivered C60 into the cells depending on their surface densities and showed cytotoxicity under photoirradiation.


Reliability and Validity of Caregivers' Fear of Falling Index When Caring for Home-Based Rehabilitation Patients With Fall-Related Fractures.
To evaluate the reliability and validity of this new measure, called the caregivers' fear of falling index (CFFI). The study surveyed home-based rehabilitation patients with fall-related fracture, and their primary caregivers. The characteristics of these patients were evaluated, and the caregivers were surveyed using the CFFI and Falls Efficacy Scale-International (FES-I). The reliability of the CFFI was assessed using item-total correlation, while the validity of the CFFI was evaluated through correlation coefficients calculated between the CFFI and the FES-I. The participants were 51 patient-caregiver pairs. The internal consistency of the CFFI showed an alpha coefficient of 0.904. No items were excluded in the corrected item-total correlations. The CFFI showed a moderate correlation with FES-I (r=0.432, p=0.002). This study found the CFFI to be a reliable and valid tool for measuring the primary caregivers' fear. The CFFI may be a useful tool for healthcare professionals to identify and supporting these primary caregivers.


Work-related traffic crashes: a record linkage study.
To examine the characteristics of work-related traffic crashes involving drivers in New South Wales (NSW), Australia. Probabilistic data record linkage were used to merge police crash records and workers compensation data for the period 1998-2002. The record linkage identified 13,124 drivers who were injured or died as a result of work-related traffic crash in New South Wales over the 5-year period. Approximately three quarters of driver casualties occurred during commuting (74.8%) with the rest occurring in the course of work. Male drivers made up around three quarters of these crashes and 93% of those that resulted in a fatality. Transport workers were the most frequent victims of work-related crashes while on duty (20.8%), with drivers of heavy trucks representing about half (48%) of all fatalities resulting from on duty work-related crashes. Nearly 1 in 6 male drivers were speeding at the time of the crash (15%, 95% CI 14.2-15.7) compared to less than 1 in 10 female drivers (9%, 95% CI 8.3-9.8) of female drivers. Male drivers were also significantly more likely to be fatigued at the time of the crash 7.6% (95% CI 7.0-8.2) compared to females 4.2% (95% CI 3.7-4.8). No significant difference was observed in the proportion of crashes involving fatigue between on duty and commuting traffic crashes. The study demonstrates the value of record linkage techniques in addressing some of the limitations of work-related data systems and in providing a more complete picture of the circumstances of occupational road crashes.


Transcription blockage by DNA damage in nucleotide excision repair-related neurological dysfunctions.
Human genetic syndromes deficient in nucleotide excision repair (NER), such as xeroderma pigmentosum and Cockayne syndrome, may present neurological abnormalities and premature aging symptoms. Unrepaired endogenously generated DNA damage that hampers transcription is a strong candidate that contributes to the development of these severe effects in neuronal tissue. Endogenous lesions include those generated due to byproducts of cellular metabolisms, such as reactive oxygen species. This review presents much of the evidence on the mechanisms related to neurodegenerative processes associated with DNA damage responses. The primary focus is on the effects of the transcription machinery, including the accumulation of DNA•RNA hybrids (R-loops) that, in turn, influence DNA damage and repair metabolism. Moreover, several neuronal tissues present higher expression of long genes, a genomic subset more affected by DNA lesions, which may explain part of the neurological abnormalities in these patients. Also, neuronal tissues have different DNA repair capabilities that might result in different neurological consequences, as observed in patients and NER deficient animal models. The better understanding of how the accumulation of transcription blocking lesions can lead to neurological abnormalities and premature aging-like phenotypes may assist us in finding potential biomarkers and therapeutic targets that might improve the lives of these patients, as well as other neurological disorders in the general population.


Risk of a second consecutive first-trimester spontaneous abortion in women who conceive with menotropins.
It is generally recognized that a spontaneous abortion rate of approximately 25% exists in human menopausal gonadotropin/human chorionic gonadotropin (hMG/hCG)-induced pregnancies. Despite this, little is known regarding the prognosis of future menotropin-induced pregnancies in women who abort in their first hMG pregnancy. We retrospectively reviewed the obstetrical outcome of women who achieved two or more menotropin pregnancies between the years 1980 and 1987. Nineteen of 40 patients (48%) whose first hMG pregnancy ended in an early spontaneous abortion went on to abort in a second hMG pregnancy, as compared with only 1 of 15 women (6.7%) whose first hMG pregnancy was successful. Age, parity, weight, height, and plasma estradiol levels at hCG administration did not differ between the two groups. From this data we conclude that women whose first hMG pregnancy results in a spontaneous abortion are at high risk for another spontaneous abortion in a subsequent menotropin conception.


Association between ability to form biofilm and virulence factors of poultry extra-intestinal Campylobacter jejuni and Campylobacter coli.
Campylobacter species are known to be able to produce biofilm, which represents an ideal protective environment for the maintenance of such fragile bacteria. Since the genetic mechanisms promoting biofilm formation are still poorly understood, in this study we assessed the ability of C. jejuni (n = 7) and C. coli (n = 3) strains isolated from diseased poultry, and previously characterized by whole genome sequencing, to form biofilm. The in vitro analyses were carried out by using a microtiter based protocol including biofilm culturing and fixation, staining with crystal violet, and measurement of the optical density (OD570). The ability to form biofilm was categorized into four classes (no, weak, moderate, and strong producers). Potential correlations between OD570 and the presence/absence of virulence determinants were examined. The C. jejuni were classified as no (n = 3), weak (n = 2), and moderate (n = 2) biofilm producers; however, all possessed genes involved in chemotaxis, adhesion, and invasion to the host cells. No genes present exclusively in biofilm producers or in non-biofilm producers were identified. All C. coli were classified as weak producers and showed a similar set of virulence genes between each other. A trend of increased mean OD570 was observed in the presence of flaA and maf7 genes. No association between biofilm production classes and the explanatory variables considered was observed. The results of this study suggest that further investigations are needed to better identify and characterize the genetic determinants involved in extra-intestinal Campylobacter biofilm formation.


Tertiary Gleason pattern 5 in Gleason 7 prostate cancer predicts pathological stage and biochemical recurrence.
Gleason sum 7 prostate cancers are a heterogeneous group with diverse tumor behaviors and disease outcomes. Tertiary Gleason patterns are reported with increasing frequency, particularly in prostatectomy pathology reports. We studied the pathological and biochemical outcome following radical prostatectomy in men with Gleason sum 7 and tertiary Gleason pattern 5. We reviewed 1,110 cases of clinically localized prostate cancer treated with primary radical prostatectomy between January 1998 and August 2006 through a prospectively collected prostate cancer database. Patients who underwent neoadjuvant or adjuvant hormonal deprivation, radiation or systemic chemotherapy were excluded. Of the 1,110 patients 509 had Gleason sum 7 cancer. Tertiary Gleason pattern was present in 66 of 509 cases (13%) and it was absent in 443 (87%). On multivariate analysis tertiary Gleason pattern 5 was associated with higher pT stage (OR 2.55, 95% CI 1.40-4.65) and biochemical recurrence (HR 1.78, 95% CI 1.00-3.17). On subgroup analysis when patients with Gleason sum 3 + 4 + 5 and 4 + 3 + 5 were compared to their respective referent groups without the tertiary Gleason pattern, the 2 groups showed a trend toward higher pathological stage and prostate specific antigen progression. Patients with Gleason sum 3 + 4 with no tertiary pattern had higher PSA recurrence-free probability than those with Gleason sum 3 + 4 + 5 or 4 + 3 and patients with Gleason sum 4 + 3 + 5 had the lowest PSA recurrence-free probability. In patients with Gleason sum 7 prostate cancer tertiary Gleason grade 5 is significantly associated with higher pT stage and biochemical recurrence. Larger studies are needed to assess the predictive value of tertiary grade compared to other established parameters in predicting the long-term oncological outcome after radical prostatectomy.


Bronchodilatory activity and pharmacokinetics of new xanthines in guinea-pigs.
1. The in vitro biological activities and the effect of protein binding on the relaxant effects in vivo of N-3-alkylxanthine and N-3-alkyl-N-1-methylxanthine derivative were investigated in guinea-pigs. 2. A significantly positive correlation was observed among the in vitro muscle relaxant activity, the cyclic adenosine monophosphate (cAMP) phosphodiesterase (PDE) inhibitory activity and the protein-binding potency of xanthine derivatives. However, there was a weak relationship between these activities and affinity for adenosine receptors. 3. When theophylline, enprofylline and 1-methyl-3-propylxanthine (MPX) were injected intravenously in guinea-pigs, their ED50 values were 6.1, 3.3 and 1.0 mg/kg, respectively. Plasma concentrations of these drugs obtained following the intravenous injection of the ED50 approximated the theoretically effective concentration (EC50) predicted from both the relaxant effects in vitro and the protein binding parameters. A good linear correlation was observed between bodyweight in four species (rats, guinea-pigs, rabbits and humans) and certain pharmacokinetic parameters of enprofylline and theophylline. 4. The present study indicates that differences in the relaxant effects of these drugs in vitro and in vivo can be explained in part by protein binding, and that the protein binding of these xanthine bronchodilators is an important determinant for their pharmacological activity. Guinea-pigs provide a useful model for studying pharmacodynamic-pharmacokinetic relationships of new bronchodilators.


Prevalence of depression and anxiety symptoms and their influence factors during menopausal transition and postmenopause in Beijing city.
To investigate the prevalence of depression and anxiety symptoms and their influence factors in women during menopausal transition and postmenopause. A cross-sectional investigation was conducted with a composed questionnaire on general conditions, social support scoring, the Zung self-evaluating depression and anxiety scoring. All of the parameters were input into a database and analyzed with t-test, chi(2) and logistic regression using SPSS. A total of 1280 women aged 45-59 in Beijing city were interviewed with the questionnaire mentioned above. The prevalence of depression symptoms and anxiety in these women was 306 (23.9%) and 131 (10.2%), respectively. Risk factors associated with depression included strait financial status, social support, dyspareunia and dry vagina, hot flashes and sweating, satisfaction with family, children fail college or job and divorced or separated. Risk factors associated with anxiety included history of premenstrual dysphoric disorder (PMDD), hot flashes, vaginal dryness or dyspareunia and some negative life events. Depression and anxiety were common symptoms in Chinese women during menopausal transition and postmenopause. Some psycho-social factors may play a role in the prevalence of them.


Development of a new equation in fuzzy logic analysis for ascertaining appropriate dose of gamma irradiation of virgin coconut oil.
Our previous investigation had established 4.2 kGy to be the appropriate dosage of gamma irradiation for removal of obnoxious rancid-acid-odor of virgin coconut oil (VCO) on the basis of sensory and electronic nose (e nose) studies. This study endeavored to revalidate the sensory data employing fuzzy logic analysis. An equation has been developed for the first time for deriving defuzzified scores, when the sum of the first and third coordinates of the triplet (a b c) of overall sensory score was greater than 100, i.e. (a + c) > 100. This study reaffirmed 4.2 kGy to be the most preferred dose for deodorization of VCO. Besides, ranking of the VCO samples were similar by either approach. •According to the fuzzy logic method, overall sensory scores were assigned to the VCO samples under investigation, these sensory scores have been represented by a triangle and a polygon when (a+c) is less and more than100, respectively.•The coordinates of the polygon were determined and a new equation has been developed for evaluating defuzzified scores, which has been validated by similarity value analysis.•This new methodology of fuzzy logic analysis can be used to rank samples rapidly and reliably, without any complexity of conventional similarity value approach.


Innovative technique for enclosed morcellation using a surgical glove.
To describe an innovative approach for enclosed morcellation using a surgical glove in multiport laparoscopic surgery. Power morcellation was performed within an insufflated surgical glove in a completely enclosed manner between January and May 2014. The specimen was placed into the glove within the abdomen. The glove opening and thumb were exteriorized through the umbilical and left lower abdominal trocar incisions, respectively. The optical trocar and optic were inserted into the glove, which was then insufflated. The thumb tip was cut, and a power morcellator was inserted through this finger. The morcellation was accomplished within the completely enclosed glove. The thumb tip was closed, and the glove, containing residual specimens and bloody fluid, was removed from the abdomen through the umbilical incision. Thus, the risks of bag piercing and leakage during contained power morcellation were eliminated. Demographic and operative data were collected and analyzed for all cases. Thirty multiport laparoscopic myomectomy and morcellation procedures were performed during the study period. The median operative time was 85 minutes (range 60-140 minutes). The median morcellation preparation time, total morcellation time, and withdrawal time were 6 (range 4.5-14), 32 (range 15-55), and 1.2 (range 1-1.5) minutes, respectively. No intraoperative complications or bag ruptures were recorded. With our innovative technique, a disposable latex glove can be used for an enclosed morcellation that avoids piercing the enclosure container within the abdominal cavity, thereby offering decreased risks related to bag perforation and leakage compared with previous contained power morcellation techniques. III.


Cross-fused ectopic multicystic dysplastic kidney with associated ureterocele.
We describe a case of the unique congenital anomaly of cross-fused ectopic multicystic dysplastic kidney with associated ureterocele and demonstrate the usefulness of magnetic resonance imaging in fetal imaging.


Nutrient removal in an algal membrane photobioreactor: effects of wastewater composition and light/dark cycle.
Graesiella emersonii was cultivated in an osmotic membrane photobioreactor (OMPBR) for nutrients removal from synthetic wastewater in continuous mode. At 1.5 days of hydraulic retention time and under continuous illumination, the microalgae removed nitrogen (N) completely at influent NH4+-N concentrations of 4-16 mg/L, with removal rates of 3.03-12.1 mg/L-day. Phosphorus (P) removal in the OMPBR was through biological assimilation as well as membrane rejection, but PO43--P assimilation by microalgae could be improved at higher NH4+-N concentrations. Microalgae biomass composition was affected by N/P ratio in wastewater, and a higher N/P ratio resulted in higher P accumulation in the biomass. The OMPBR accumulated about 0.35 g/L biomass after 12 days of operation under continuous illumination. However, OMPBR operation under 12 h light/12 h dark cycle lowered biomass productivity by 60%, which resulted in 20% decrease in NH4+-N removal and nearly threefold increase in PO43--P accumulation in the OMPBR. Prolonged dark phase also affected carbohydrate accumulation in biomass, although its effects on lipid and protein accumulation were negligible. The microalgae also exhibited high tendency to aggregate and settle, which could be attributed to reduction in cell surface charge and enrichment of soluble algal products in the OMPBR. Due to a relatively shorter operating period, membrane biofouling and salt accumulation did not influence the permeate flux significantly. These results improve the understanding of the effects of N/P ratio and light/dark cycle on biomass accumulation and nutrients removal in the OMPBR.


Targeting the honey bee gut parasite Nosema ceranae with siRNA positively affects gut bacteria.
Gut microbial communities can contribute positively and negatively to host health. So far, eight core bacterial taxonomic clusters have been reported in honey bees. These bacteria are involved in host metabolism and defenses. Nosema ceranae is a gut intracellular parasite of honey bees which destroys epithelial cells and gut tissue integrity. Studies have shown protective impacts of honey bee gut microbiota towards N. ceranae infection. However, the impacts of N. ceranae on the relative abundance of honey bee gut microbiota remains unclear, and has been confounded during prior infection assays which resulted in the co-inoculation of bacteria during Nosema challenges. We used a novel method, the suppression of N. ceranae with specific siRNAs, to measure the impacts of Nosema on the gut microbiome. Suppressing N. ceranae led to significant positive effects on microbial abundance. Nevertheless, 15 bacterial taxa, including three core taxa, were negatively correlated with N. ceranae levels. In particular, one co-regulated group of 7 bacteria was significantly negatively correlated with N. ceranae levels. N. ceranae are negatively correlated with the abundance of 15 identified bacteria. Our results provide insights into interactions between gut microbes and N. ceranae during infection.


The AIDS epidemic in the city of Copenhagen, Denmark: potential years of life lost and impact on life expectancy.
This study seeks to describe the impact of AIDS on the city of Copenhagen by estimating potential years of life lost (PYLL) before the age of 65 years and to estimate the impact of AIDS deaths on life expectancy for males and females. All AIDS cases reported to the national AIDS surveillance register for residents in the city of Copenhagen in the period 1983-98 were included. For comparative purposes data were obtained on six other causes of death: accidents, suicide, lung cancer, ischaemic heart disease, testicular cancer, and breast cancer. Overall, deaths from AIDS accounted for 8% of all PYLL in men and showed an increasing tendency from 1983 to 1991, when it became the leading cause of PYLL. AIDS had most impact in men in the age group 25-44 years and accounted for 29% of all PYLL in this group at the peak in 1993, decreasing significantly after the introduction of anti-retroviral treatments to 5% of PYLL in 1998. Other leading causes of PYLL, accidents and suicide, also showed a decreasing tendency over the years, but of a much smaller magnitude than AIDS. The impact of AIDS in women was more modest. In the entire study period suicide, accidents, and breast cancer were the leading causes of PYLL in women. It was shown that AIDS deaths at the top of the epidemic in 1991-95 were responsible for a loss of 0.76 years in life expectancy for men and 0.08 years for women. AIDS has had a considerable impact on potential years of life lost. A significant decline in AIDS deaths has been seen since 1995 with an effect on life expectancy for men in the city of Copenhagen.


The further spread of Aedes japonicus japonicus (Diptera, Culicidae) towards northern Germany.
After its first detection in 2008 in the south German federal state of Baden-Wuerttemberg, another distinct population of the invasive Asian bush mosquito Aedes japonicus japonicus was unexpectedly found in western Germany in 2012. Range expansion had already been observed for the southern German population and was anticipated for the western German one. Here, we report on a third, apparently independent and even more northerly German colonization area of Aedes j. japonicus in southern Lower Saxony and northeastern North Rhine-Westphalia, which was discovered in spring 2013. In a snapshot study, intended to determine the presence or absence of Aedes j. japonicus in an area close to Hanover, the capital of the northern German federal state of Lower Saxony, where a specimen had been collected in late 2012, central water basins of cemeteries were checked for pre-imaginal mosquito stages at the beginning of the mosquito season 2013. Almost 20% of the inspected cemeteries were found positive (25 out of 129), with many of them being located in towns and villages close to the motorways A2 and A7. Being of Far Eastern origin, the Asian bush mosquito is well adapted to moderate climates and appears to be further expanding its distribution area in Central Europe. As it is a proven laboratory vector of several mosquito-borne disease agents, its present and future distribution areas should be carefully monitored.


Argininosuccinic aciduria: metabolic studies and effects of treatment with keto-analogues of essential amino acids.
A 22 years old female with the late-onset of argininosuccinic aciduria was successfully treated for 5 months with a mixture of essential amino acids and their keto-analogues. There was a marked change in plasma ammonia, plasma amino acids and argininosuccinic acid excretion. A long term anabolic response was reflected by an increase of total serum proteins and serum albumin by about 1 g/dl during the first 5 months of treatment. There was a striking improvement in the patient's seizure disorder following institution of the keto-analogue therapy.


A pharmacogenetic inducible approach to the study of NMDA/alphaCaMKII signaling in synaptic plasticity.
We recently introduced an inducible pharmacogenetic approach where pharmacological manipulations can be used to reveal recessive mutant phenotypes in a temporally controlled manner. This approach takes advantage of synergisms between pharmacological and genetic manipulations to alter the function of specific signaling pathways. For example, mice heterozygous for a point mutation (T286A) in the alpha-calcium/calmodulin-dependent kinase II (alphaCaMKII) gene show normal learning and memory. However, a concentration of an NMDA receptor antagonist (CPP) that does not affect learning in wild-type (WT) littermates, reveals learning deficits in this heterozygote (alphaCaMKII(T286A+/-)). Here, we show that pretetanic application of a concentration of CPP (0.1 microM) ineffective in WT hippocampal slices induced deficits in alphaCaMKII(T286A+/-) slices in hippocampal long-term potentiation (LTP), a mechanism thought to be involved in learning and memory. Importantly, posttetanic application of CPP (0.1 microM) had no effect on the expression or maintenance of LTP in hippocampal slices from alphaCaMKII(T286A+/-) mice. Thus, this pharmacogenetic approach allowed us to demonstrate that NMDA receptor-dependent autophosphorylation of alphaCaMKII is required during the induction but not maintenance of LTP. This ability to temporally induce recessive mutant phenotypes could be applicable to a broad range of problems and genetic systems.


Recent contributions of structure-based drug design to the development of antibacterial compounds.
According to a Pew Research study published in February 2015, there are 37 antibacterial programs currently in clinical trials in the United States. Protein structure-based methods for guiding small molecule design were used in at least 34 of these programs. Typically, this occurred at an early stage (drug discovery and/or lead optimization) prior to an Investigational New Drug (IND) application, although sometimes in retrospective studies to rationalize biological activity. Recognizing that structure-based methods are resource-intensive and often require specialized equipment and training, the NIAID has funded two Structural Genomics Centers to determine structures of infectious disease species proteins with the aim of supporting individual investigators' research programs with structural biology methods.


Effects of heat stress on respiratory burst, oxidative damage and SERPINH1 (HSP47) mRNA expression in rainbow trout Oncorhynchus mykiss.
For rainbow trout Oncorhynchus mykiss, high temperature is a major abiotic stress that limits its growth and productivity. In this study, spleen macrophage respiratory burst (RB), serum superoxide dismutase (SOD), serum malondialdehyde (MDA) and mRNA expression of the SERPINH1 (HSP47) gene in different tissues (liver, spleen, head kidney and heart) were measured in unstressed (18 °C) and heat-stressed (25 °C) fish. Spleen macrophage RB activity, serum SOD activity and MDA content all increased significantly (P < 0.05) during heat shock, and peaked at 8, 12 and 4 h, respectively. SERPINH1 mRNA expression responded in a time- and tissue-specific manner to heat stress, which was mainly reflected in the significant up-regulation in all tissues (P < 0.05) and greater expression in the liver than the other tissues (P < 0.05). During the heat-shock recovery period, the MDA content returned to the unstressed level. These results indicate that heat shock causes cell injury, induces oxidative damage and promotes SERPINH1 mRNA expression, which plays an important protective function during heat stress in O. mykiss. In practice, close attention should be given to temperature changes in O. mykiss production to reduce the effects of high temperature.


SnapShot: cancer vaccines.
This SnapShot illustrates the main concepts and underlying biology of therapeutic vaccination in cancer. Dendritic cells (DCs) are an essential component of vaccination through their capacity to capture, process, and present antigens to T cells. We have come a long way in our understanding of what is needed to elicit therapeutic immunity when cancer escapes the natural barrier of protective immunity. This progress enables the development of novel vaccines.


Disentangling the effects of vapor pressure deficit on northern terrestrial vegetation productivity.
The impact of atmospheric vapor pressure deficit (VPD) on plant photosynthesis has long been acknowledged, but large interactions with air temperature (T) and soil moisture (SM) still hinder a complete understanding of the influence of VPD on vegetation production across various climate zones. Here, we found a diverging response of productivity to VPD in the Northern Hemisphere by excluding interactive effects of VPD with T and SM. The interactions between VPD and T/SM not only offset the potential positive impact of warming on vegetation productivity but also amplifies the negative effect of soil drying. Notably, for high-latitude ecosystems, there occurs a pronounced shift in vegetation productivity's response to VPD during the growing season when VPD surpasses a threshold of 3.5 to 4.0 hectopascals. These results yield previously unknown insights into the role of VPD in terrestrial ecosystems and enhance our comprehension of the terrestrial carbon cycle's response to global warming.


Polarization microscopy and microspectrophotometry of Sirius Red, Picrosirius and Chlorantine Fast Red aggregates and of their complexes with collagen.
A detailed quantitative analysis of the anisotropic properties of Sirius Red F3B, Picrosirius, and Chlorantine Fast Red crystals, and of their complexes with a macromolecularly oriented protein either in a pure form or as part of a tissue structure was carried out. Collagen I was used as the protein model. Linear dichroism and dispersion of birefringence were investigated in dye aggregates, in stained filaments of collagen I and in collagen bundles in sections of tendon. A positive linear dichroism, the characteristics of which varied as a function of the dye type used, was demonstrated for the dye aggregates and stained substrates. However, even thin regions of the stained tendon collagen bundles showed very high absorbances, differing from the pattern reported previously for collagen stained with another sulphonated azo dye, Xylidine Ponceau. Consequently, not all these dyes enable protein concentration and orientation to be determined in collagen-containing structures. From the linear dichroism patterns it is assumed that the long axis of the molecules of these azo dyes is mostly parallel to that of filaments of pure collagen I and statistically parallel to the long axis of collagen bundles of tendon sections. The dye aggregates and, stained pure collagen I and tendon collagen bundles exhibited birefringent images with interference colours that varied as a function of thickness and packing state of the preparations, which is in agreement with reports in the literature. The optical retardations of the collagen bundles increased by a factor of 5-6 times after staining with Picrosirius. From data on form dichroism it is concluded that when studying the macromolecular orientation of collagen preparations stained with azo dyes, the choice of the mounting medium deserves consideration.


First Complete Genome Sequence of Zika Virus (Flaviviridae, Flavivirus) from an Autochthonous Transmission in Brazil.
We report here the genome sequence of Zika virus, strain ZikaSPH2015, containing all structural and nonstructural proteins flanked by the 5' and 3' untranslated region. It was isolated in São Paulo state, Brazil, in 2015, from a patient who received a blood transfusion from an asymptomatic donor at the time of donation.


Hadamard transform capillary electrophoresis combined with laser-induced fluorometry using electrokinetic injection.
Hadamard transform capillary electrophoresis (HTCE) based on electrokinetic injection allows laser-induced fluorescence detection using a small laser, namely the laser-diode-pumped YAG laser, as an excitation source. A small hole is fabricated at the center of a capillary by laser ablation; this hole functions as an inlet port for a sample solution. Therefore, the sample solution can be introduced electrophoretically into the capillary through the small hole. Multiple sample injection is accomplished by introducing a buffer solution from the end of the capillary and the sample solution through the hole. Both solutions are injected using two sets of high-voltage power supplies and migrate toward the opposite end of the capillary. A fluorescent analyte, rhodamine B, is successfully detected in the case of both single and multiple injection according to the Hadamard sequence code. By transforming the data encoded by the Hadamard matrix, the decoded data showed an increase in the signal-to-noise (S/N) ratio by a factor of 9.8. In the case of the sample containing two amino acids labeled with rhodamine B isothiocyanate (RBITC), although the concentration of every component including free RBITC is lower than the concentration limit of detection obtained by single injection, a substantial improvement in the sensitivity is achieved and all components are identified by the Hadamard transform technique.


Reverse cholesterol transport and lipid peroxidation biomarkers in major depression and bipolar disorder: A systematic review and meta-analysis.
Major depression (MDD) and bipolar disorder (BD) are linked to immune activation, increased oxidative stress, and lower antioxidant defenses. To systematically review and meta-analyze all data concerning biomarkers of reverse cholesterol transport (RCT), lipid-associated antioxidants, lipid peroxidation products, and autoimmune responses to oxidatively modified lipid epitopes in MDD and BD. Databases including PubMed, Google scholar and SciFinder were searched to identify eligible studies from inception to January 10th, 2023. Guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed. The current meta-analysis included 176 studies (60 BD and 116 MDD) and examined 34,051 participants, namely 17,094 with affective disorders and 16,957 healthy controls. Patients with MDD and BD showed a) significantly decreased RCT (mainly lowered high-density lipoprotein cholesterol and paraoxonase 1); b) lowered lipid soluble vitamins (including vitamin A, D, and coenzyme Q10); c) increased lipid peroxidation and aldehyde formation, mainly increased malondialdehyde (MDA), 4-hydroxynonenal, peroxides, and 8-isoprostanes; and d) Immunoglobulin (Ig)G responses to oxidized low-density lipoprotein and IgM responses to MDA. The ratio of all lipid peroxidation biomarkers/all lipid-associated antioxidant defenses was significantly increased in MDD (standardized mean difference or SMD = 0.433; 95% confidence intervals (CI): 0.312; 0.554) and BD (SMD = 0.653; CI: 0.501-0.806). This ratio was significantly greater in BD than MDD (p = 0.027). In MDD/BD, lowered RCT, a key antioxidant and anti-inflammatory pathway, may drive increased lipid peroxidation, aldehyde formation, and autoimmune responses to oxidative specific epitopes, which all together cause increased immune-inflammatory responses and neuro-affective toxicity.


The first case of septic arthritis of the knee caused by Eggerthia catenaformis.
Eggerthia catenaformis has been reported as a human pathogen. We present the first case of the primary knee infection caused by Eggerthia catenaformis in a 23-year-old male patient with a knee infection, after primary anterior cruciate ligament reconstruction. Eggerthia catenaformis was confirmed by MALDI-TOF mass spectrometry from synovial fluid. The dental focus was excluded. The isolated bacterial strain showed sensitivity to all of the tested antimicrobials. However, for successful management of knee infection, besides culture-directed antibiotics therapy, arthroscopic debridement and lavage were necessary.


Predictors of Stone-Related Events in Asymptomatic Untreated Intrarenal Calculi.
Purpose: There is a lack of data on the natural history of asymptomatic intrarenal calculi. In this study, we investigate stone-related events (SREs) in patients with untreated intrarenal calculi. We also investigate predictive factors for SREs. Methods: All patients found with an asymptomatic intrarenal calculus on CT kidney, ureter, bladder managed conservatively with interval imaging for ≥6 months were included. Patients were evaluated for any SRE. The rate of event according to calculus size, location, and number of calculi was also analyzed. Multivariate logistic regression analysis was performed to determine significant predictors for SREs. Results: In total, 266 renal units from 177 patients met inclusion criteria. The mean stone size was 4.44 mm (range 1-25 mm). Duration of follow-up was 43.78 ± 26.86 months (range 6-106 months). The overall rate of SREs, including intervention (n = 80) and spontaneous stone passage after ureteral colic (n = 40), was 45.1% (n = 120/266). Stones >5 mm were more likely to lead to an event compared with stones ≤5 mm (odds ratio [OR]: 2.94; p = 0.01). Interpolar stones and stones located in multiple calices were more likely to cause a SRE than lower pole stones (OR: 2.05; p = 0.05 and OR: 2.29; p = 0.03, respectively). Conclusion: In this large series of patients with asymptomatic intrarenal calculi, the incidence of a spontaneous SRE was 45.1% after 41 months. Stone size and stone location were significant predictors for a SRE. Information from this study will enable urologists to accurately risk stratify patients with asymptomatic renal stones.


The prognostic accuracy of different QT interval measures.
The QT intervals accuracy for predicting arrhythmic death varies between studies, possibly due to differences in the selection of the lead used for measurement of the QT interval. The purpose of this study was to analyze the prognostic accuracy of all known ways to select the lead. Three institutions that used different methods for measuring QT intervals provided their QT databases. They included more than 3500 twelve-lead surface ECGs. The data represented low- and high-risk patients of the normal population (survivors vs dead from cardiovascular causes), acute myocardial infarction (survivors versus death from all causes) and remote myocardial infarction (with vs without a history of ventricular arrhythmia). The prognostic accuracy was defined as the area under the Receiver Operator Curve (ROC-area). The most accurate standard leads were I and aVL and the least accurate was AVR. The most accurate precordial lead was V4. The prognostic accuracy of the longest QT interval was higher than for any standard lead. The prognostic accuracy of the mean of the three longest QT intervals was equal to or slightly lower than for the longest QT interval. The highest prognostic accuracy is obtained with the longest QT interval. The accuracies of the lead selection methods are so different that it can explain a substantial part of the differences between otherwise similar studies in the literature. We recommend the use of the mean value of the three longest QT intervals.


The X factor in neurodegeneration.
Given the aging population, it is important to better understand neurodegeneration in aging healthy people and to address the increasing incidence of neurodegenerative diseases. It is imperative to apply novel strategies to identify neuroprotective therapeutics. The study of sex differences in neurodegeneration can reveal new candidate treatment targets tailored for women and men. Sex chromosome effects on neurodegeneration remain understudied and represent a promising frontier for discovery. Here, we will review sex differences in neurodegeneration, focusing on the study of sex chromosome effects in the context of declining levels of sex hormones during aging.


Efficacy of Michel's 'dose and move' system against Dictyocaulus viviparus infections in cattle using moxidectin as anthelmintic.
Two grazing experiments were performed to study the effect of moxidectin in a 'dose and move' system on Dictyocaulus viviparus infections in calves. In the first experiment, three groups of four calves were experimentally infected with 20 larvae of D. viviparus 7 weeks before moxidectin treatment of two of these groups. A sufficient suppression of Dictyocaulus infections was observed in a 'dose and move' group, but also in a group which stayed on contaminated pasture after treatment. In contrast, high faecal larval counts and lungworm disease were observed in July-August in a non-treated pasture control group. Development of immunity against lungworm was sufficient in all three groups, on pasture. In the second experiment, four out of 26 calves, including two groups of six calves and four tracer calves, were experimentally infected with 20 larvae of D. viviparus 7 weeks before moxidectin treatment combined with a move of one of the groups. No lungworm disease was observed in this 'dose and move' group. In a pasture control group high faecal larval counts and severe clinical disease were observed in August-September and one calf had to be euthanized. Although a mean burden of 129 immature lungworms was present at the time of treatment, development of immunity appeared to be low in the 'dose and move group'. In contrast, high levels of immunity had developed in the pasture control group.


Incidences of aortic and mitral valve strands in patients with migraine with aura.
To analyze the potential association between valvular strands and migraine with aura. During a 1-year period,transesophageal echocardiography was performed in 51 consecutive patients with migraine with aura and 75 control subjects who underwent transesophageal echocardiography for other purposes and had no history of migraine. The presence of aortic and mitral valve strands was evaluated. The incidence of valvular strands was 21.5% (11/51) in migraine patients and 28.0% (21/75) in control subjects (Χ²=0.663, P=0.416). The incidence of patent foramen ovale was significantly higher in patients with migraine with aura than in control subjects (50.9% vs.29.3%) (Χ²=6.302, P=0.012). The incidence of aortic valve strands was significantly higher than that of mitral valve strands in migraine patients (Χ²=4.320,P=0.038). Valvular strands are not associated with migraine with aura and show little clinical significance.


Uncovering the processes of microbial community assembly in the near-surface sediments of a climate-sensitive glacier-fed lake.
Glacier-fed lakes are characterized by cold temperatures, high altitudes, and nutrient-poor conditions. Despite these challenging conditions, near-surface sediments of glacier-fed lakes harbor rich microbial communities that are critical for ecosystem functioning and serve as a bridge between aquatic ecology and the deep subsurface biosphere. However, there is limited knowledge regarding the microbial communities and their assembly processes in these sediments, which are highly vulnerable to climate change. To fill this knowledge gap, this study systematically analyzed environmental variables, microbial communities, diversity, co-occurrence relationships, and community assembly processes in the near-surface sediments of a glacier-fed lake in the Tibetan Plateau. The results revealed distinct vertical gradients in microbial diversity and subcommunities, highlighting the significant influence of selection processes and adaptive abilities on microbial communities. Specifically, specialists played a crucial role within the overall microbial communities. Microbial assembly was primarily driven by homogeneous selection, but its influence declined with increasing depth. In contrast, homogenizing dispersal showed an opposite pattern, and the bottom layer exhibited heterogeneous selection and undominated processes. These patterns of microbial assembly were primarily driven by environmental gradients, with significant contributions from processes associated to ammonium and organic matter deposition, as well as chemical precipitation in response to a warming climate. This study enhances our understanding of the microbial communities and assembly processes in the near-surface sediments of glacier-fed lakes and sheds light on geo-microbiological processes in climate-sensitive lacustrine sediments.


Notch signaling plays a key role in cardiac cell differentiation.
Results from lineage tracing studies indicate that precursor cells in the ventricles give rise to both cardiac muscle and conduction cells. Cardiac conduction cells are specialized cells responsible for orchestrating the rhythmic contractions of the heart. Here, we show that Notch signaling plays an important role in the differentiation of cardiac muscle and conduction cell lineages in the ventricles. Notch1 expression coincides with a conduction marker, HNK-1, at early stages. Misexpression of constitutively active Notch1 (NIC) in early heart tubes in chick exhibited multiple effects on cardiac cell differentiation. Cells expressing NIC had a significant decrease in expression of cardiac muscle markers, but an increase in expression of conduction cell markers, HNK-1, and SNAP-25. However, the expression of the conduction marker connexin 40 was inhibited. Loss-of-function study, using a dominant-negative form of Suppressor-of-Hairless, further supports that Notch1 signaling is important for the differentiation of these cardiac cell types. Functional studies show that the expression of constitutively active Notch1 resulted in abnormalities in ventricular conduction pathway patterns.


Performance of A1C for the classification and prediction of diabetes.
Although A1C is now recommended to diagnose diabetes, its test performance for diagnosis and prognosis is uncertain. Our objective was to assess the test performance of A1C against single and repeat glucose measurements for diagnosis of prevalent diabetes and for prediction of incident diabetes. We conducted population-based analyses of 12,485 participants in the Atherosclerosis Risk in Communities (ARIC) study and a subpopulation of 691 participants in the Third National Health and Nutrition Examination Survey (NHANES III) with repeat test results. Against a single fasting glucose ≥126 mg/dl, the sensitivity and specificity of A1C ≥6.5% for detection of prevalent diabetes were 47 and 98%, respectively (area under the curve 0.892). Against repeated fasting glucose (3 years apart) ≥126 mg/dl, sensitivity improved to 67% and specificity remained high (97%) (AUC 0.936). Similar results were obtained in NHANES III against repeated fasting glucose 2 weeks apart. The accuracy of A1C was consistent across age, BMI, and race groups. For individuals with fasting glucose ≥126 mg/dl and A1C ≥6.5% at baseline, the 10-year risk of diagnosed diabetes was 88% compared with 55% among those individuals with fasting glucose ≥126 mg/dl and A1C 5.7-<6.5%. A1C performs well as a diagnostic tool when diabetes definitions that most closely resemble those used in clinical practice are used as the "gold standard." The high risk of diabetes among individuals with both elevated fasting glucose and A1C suggests a dual role for fasting glucose and A1C for prediction of diabetes.


Short- and long-term mortality of subarachnoid hemorrhage according to hospital volume and severity using a nationwide multicenter registry study.
Recent improvements in treatment for subarachnoid hemorrhage (SAH) have decreased the mortality rates; however, the outcomes of SAH management are dependent on many other factors. In this study, we used nationwide, large-scale, observational data to investigate short- and long-term mortality rates after SAH treatment and the influence of patient severity and hospital volume. We selected patients with SAH treated with clipping and coiling from the South Korean Acute Stroke Assessment Registry. High- and low-volume hospitals performed ≥20 clipping and coiling procedures and <20 clipping and coiling procedures per year, respectively. Short- and long-term mortality were tracked using data from the Health Insurance Review and Assessment Service. Among 2,634 patients treated using clipping and coiling, 1,544 (58.6%) and 1,090 (41.4%) were hospitalized in high- and low-volume hospitals, respectively, and 910 (34.5%) and 1,724 (65.5%) were treated with clipping and coiling, respectively. Mortality rates were 13.5, 14.4, 15.2, and 16.1% at 3 months, 1, 2, and 4 years, respectively. High-volume hospitals had a significantly lower 3-month mortality rate. Patients with mild clinical status had a significantly lower 3-month mortality rate in high-volume hospitals than in low-volume hospitals. Patients with severe clinical status had significantly lower 1- and 2-year mortality rates in high-volume hospitals than in low-volume hospitals. Short- and long-term mortality in patients with SAH differed according to hospital volume. In the modern endovascular era, clipping and coiling can lead to better outcomes in facilities with high stroke-care capabilities.


Supplementation with 200 mg/day docosahexaenoic acid from mid-pregnancy through lactation improves the docosahexaenoic acid status of mothers with a habitually low fish intake and of their infants.
The supply of docosahexaenoic acid (DHA, 22:6omega-3), important for fetal/infant neurodevelopment, depends on the maternal fatty acid (FA) status, which may be marginal in central Europe. Therefore, we investigated the effect of a daily vitamin/mineral supplement with and without 200 mg DHA from mid-pregnancy through lactation on the DHA concentrations in maternal and infant red blood cell phospholipids (RBC%), and in breast milk FA (%). At 21 weeks' gestation, 144 women were enrolled into a randomised, double-blind clinical trial receiving daily: (1) a basic vitamin-mineral supplement (Vit/Min group), (2) Vit/Min plus 4.5 g fructo-oligosaccharide (FOS group), or (3) Vit/Min plus 4.5 g FOS plus 200 mg fish oil-derived DHA (DHA-FOS group). FAs were determined by capillary gas-liquid chromatography. While maternal RBC-DHA% at enrolment was not different, at 37 weeks gestation, and 3 months after delivery RBC-DHA% were significantly higher in the DHA-FOS group. The breast milk DHA% was twice as high in the DHA-FOS group (0.50%) than in the two others (0.25 %) (p < 0.001), and the ratio ARA/DHA in the DHA-FOS group was 1.0 +/- 0.43, in the others 2.1 +/- 0.43 (p < 0.001). The RBC-DHA% of the infants in the DHA-FOS group was also significantly higher, and correlated significantly with maternal RBC-DHA% before and 3 months after delivery. In central Europe, a dose of 200 mg/day DHA from mid-pregnancy through lactation seems appropriate to improve the DHA status of mothers and infants.


Adaptation and validation of the Portuguese version of the regulation of eating behavior scale (REBSp).
The aim of present study was two-fold: i) to translate and adapt the Regulation of Eating Behavior Scale to Portuguese (REBSp), and ii) to analyze its psychometrics properties (factorial validity with gender invariance analyses, reliability and construct validity). The study sample was composed by 471 Portuguese participants (68.4% females) with a mean age of 30.5 years (SD = 11.2). Structural equation modeling was used to verify the psychometric properties of the scale using SPSS v. 23.0 and AMOS 24.0 software. The analysis showed that the Portuguese 24-item scale presented a good fit, achieving good reliability and convergent validity. Some issues arose with discriminant validity within autonomous and controlled regulations, discussed in light of the simplex pattern expected by self-determination theory literature. Additionally, the scale presented concurrent validity and evidence of gender measurement invariance. Latent mean analysis between genders showed that women presented higher means for intrinsic motivation and integrated regulation when compared to men. In conclusion, analyses suggest that the 24-item Portuguese version of REBS can be used safely to assess the eating regulation in both genders.


Purification of highly radioactive mouse interferon produced by Ehrlich ascites tumour cells induced by Sendai virus.
Mouse interferon (IFN) was produced to high titres after induction of Ehrlich ascites tumour cells with Sendai virus by using an improved procedure. The IFN molecules were labelled during their synthesis by the incorporation of [3H]leucine and [3H]lysine. Electrophoretically homogeneous labelled IFN with a molecular weight of 34000 was obtained after a two-step purification procedure using poly(I)-agarose and octyl-Sepharose column chromatography followed by sodium dodecyl sulphate-polyacrylamide gel electrophoresis. The specific radioactivity of this IFN was about 10 ct/min/IFN unit.


Primary feather molt and serum luteinizing hormone concentration in chukar partridge (Alectoris chukar) during a photoperiodically induced molt with or without fasting.
In two experiments, 135 adult chukar partridge of two genetic lines, one selected for high egg production and a random-bred control line, were induced to molt by reducing photoperiod from 16 hr light/day to 8 hr light/day on Day 0. In Experiment 1, feed was removed from approximately half the birds on Day 0 and returned on Day 7. Birds in Experiment 2 were not fasted. Photoperiod was increased to 16 hr light/day on Day 56. Primary feather molt scores, body weights, and, in Experiment 2, serum luteinizing hormone (LH) levels were monitored weekly through Day 85. Prior to the short day period, birds selected for high egg production and females had lower molt scores than controls or males, respectively. Fasting had no effect on molt scores, egg production, or body weights (except during the fasting period). Selected-line birds returned to lay approximately 3 days earlier and laid approximately 16 more eggs during the second production period than controls. Six days before photoperiod was reduced, immunoreactive serum LH levels were 5 to 8 ng/ml; they declined during short days to about 4 ng/ml. Within 8 days after relighting, LH levels increased to approximately 33 ng/ml in males and 18 ng/ml in females. Luteinizing hormone levels remained elevated in males throughout the subsequent 4 weeks but declined in females as egg production resumed.


The Landscape of PDK1 in Breast Cancer.
Given that 3-phosphoinositide-dependent kinase 1 (PDK1) plays a crucial role in the malignant biological behaviors of a wide range of cancers, we review the influence of PDK1 in breast cancer (BC). First, we describe the power of PDK1 in cellular behaviors and characterize the interaction networks of PDK1. Then, we establish the roles of PDK1 in carcinogenesis, growth and survival, metastasis, and chemoresistance in BC cells. More importantly, we sort the current preclinical or clinical trials of PDK1-targeted therapy in BC and find that, even though no selective PDK1 inhibitor is currently available for BC therapy, the combination trials of PDK1-targeted therapy and other agents have provided some benefit. Thus, there is increasing anticipation that PDK1-targeted therapy will have its space in future therapeutic approaches related to BC, and we hope the novel approaches of targeted therapy will be conducive to ameliorating the dismal prognosis of BC patients.


Analysis of polynuclear aromatic hydrocarbons in olive oil after solid-phase extraction using a dual-layer sorbent cartridge followed by high-performance liquid chromatography with fluorescence detection.
A simple and easy direct solid-phase extraction (SPE) method was developed for the analysis of polynuclear aromatic hydrocarbons (PAHs) in olive oil using a dual-layer cartridge containing activated Florisil and a mixture of octadecyl (C18)-bonded and zirconia-coated silicas. Undiluted olive oil was applied directly to the SPE cartridge, and the sample was eluted with acetonitrile solvent. Background in the extract was found to be low enough for either gas chromatography-mass spectrometry (GC-MS) or high-performance liquid chromatography with fluorescence detection (HPLC-FLD) analysis. Average recoveries for 16 different PAHs from spiked olive oil replicates were >75%, with intraday precisions of <20% relative standard deviation (% RSD). Detection limits ranged from 0.2 to 1.0 μg/kg and, specifically for the PAHs listed in EC Regulation 835/2011, benzo(a)anthracene, chrysene, benzo(b)fluoranthene, and benzo(a)pyrene, were from 0.3 to 0.7 μg/kg. The method was then applied to determine the PAH content present in commercial samples of refined versus extra-virgin olive oils.


Flow cytometric analysis of the neutralizing immune response against infectious bursal disease virus using reticuloendotheliosis virus-transformed lymphoblastoid cell lines.
Infectious bursal disease virus (IBDV) is a lymphotropic virus with cytocidal effect on B lymphocytes of the bursa of Fabricius. We investigated the susceptibility of clonal populations of reticuloendotheliosis virus-transformed chicken B lymphocytes of both spleen and bursal origin to IBDV infection. The infected cells were metabolically-labelled and the viral polypeptides were analyzed by immunoprecipitation using monoclonal antibodies (MAbs). Virus adsorption and the effects of neutralizing convalescent antisera and MAbs on virus attachment were studied using flow cytometry. The results of the study indicate firstly that the transformed B cells support virus replication and provide an efficient system for studying IBDV-lymphocyte interactions. Secondly, results obtained also showed that the most potent neutralizing antibodies may not be those involved in preventing the receptor-mediated viral attachment but rather those involved in the inhibition of downstream events such as virus penetration or uncoating.


In situ mapping of community-level cellular response with catalytic microbiosensors.
Chemotaxis, the migration of cells in the direction of a spatial chemical gradient, is important in disease progression, microbial ecology, and bioremediation. The ability to map chemoattractant gradients and the corresponding cellular growth and motility patterns is essential to the study of chemotaxis. Microelectrodes and microbiosensors have the potential to measure chemoattractant gradients with high spatial resolution. In this study, Clark-type amperometric microelectrodes and microbiosensors were used to measure solute concentrations gradients generated by a chemotactic band of Escherichia coli in a semi-solid gel. A computerized image analysis system was used to simultaneously measure the cellular concentration profile across the chemotactic band. The experimental results compared favorably with a mathematical model of solute and cell transport in the gel. Scanning electron micrographs (SEM) of micro(bio)sensor tips taken after 6 months of use showed evidence of degradation, including adhesion of foreign particles to the glass body, the adhesion of a small gel capsule to the sensor tip, and separation of the bio-interface from the tip. A needle-type microbiosensor was constructed to better protect the tip and hence increase the ruggedness of the microbiosensors.


Fusion leads to effective segregation of damage during cell division: An analytical treatment.
High levels of cellular damage are associated with impairment of cellular function and cell death. Partitioning the damage into a fraction of cells in the population improves population fitness and survival. We have previously shown that protein aggregates, resulting from misfolded, damaged proteins, fuse with each other leading to damage partitioning during cell division. Here, using an analytical treatment of aggregate fusion in dividing cells we present analytical expressions for two measures of damage partition: aggregate mass partition asymmetry between two dividing cells and standard deviation of total aggregate mass across the population. The scaling laws obtained demonstrate how damage partition may generally depend on characteristics of the cellular processes, facilitating better understanding of damage segregation in biological cells.


An Electronic Shared Decision-Making App to Improve Asthma Outcomes: A Randomized Controlled Trial.
Shared decision-making (SDM) incorporates patient values and preferences to optimize asthma management decisions. Available asthma SDM aids primarily focus on medication selection. To assess the usability, acceptability, and preliminary effectiveness of an electronic SDM application, the ACTION (Active Conversation in asthma Treatment shared decisION-making) app, that addressed medication, nonmedication, and COVID-19 concerns for asthma. In this pilot study, 81 participants with asthma were randomized into the control arm or ACTION app intervention. The ACTION app was completed 1 week before a clinic visit, and responses were shared with the medical provider. The primary outcomes were patient satisfaction and SDM quality. Next, ACTION app users (n = 9) and providers (n = 5) provided feedback through separate virtual focus groups. Sessions were coded by comparative analysis. The ACTION app group scored higher agreement that providers adequately addressed COVID-19 concerns compared with the control group (4.4 vs 3.7, P = .03). Although the ACTION app group had a higher total 9-item Shared Decision-Making Questionnaire score, this did not reach statistical significance (87.1 vs 83.3, P = .2). However, the ACTION app group demonstrated stronger agreement that their physician knew exactly how they wanted to be involved in decision-making (4.3 vs 3.8, P = .05), providers asked about preferences (4.3 vs 3.8, P = .05), and that different options were thoroughly weighed (4.3 vs 3.8, P = .03). Major focus group themes included that the ACTION app was practical and established a patient-centered agenda. An electronic asthma SDM app that incorporates patient preferences regarding nonmedication-related, medication-related, and COVID-19-related concerns is well accepted and can improve patient satisfaction and SDM.


Minimally invasive transforaminal lumbar interbody fusion and spondylolisthesis.
The purpose of this study was to assess the clinical and radiological outcomes of minimally invasive transforaminal lumbar interbody fusion (MI-TLIF) surgery for lumbar spondylolisthesis. A prospective analysis was conducted of 23 consecutive patients with grade I or grade II lumbar spondylolisthesis who underwent a MI-TLIF using image guidance between August 2008 and September 2010. The patient group comprised 13 males and 10 females (mean age 57 years), 22 of whom underwent single level fusion and one patient with a two level fusion. All patients underwent postoperative CT scans to assess pedicle screw and cage placement and fusion at six months. The Oswestry Disability Index (ODI) scores were recorded preoperatively and at the six-month follow-up. We found that 22 of 23 (95.7%) patients showed evidence of fusion at six months with a mean improvement of 26.7 on ODI scores. The mean length of hospital stay was four days. The mean operative time was 172 minutes. Anatomical reduction of the spondylolisthesis was complete in 16 patients and incomplete in seven. Regarding complications, we observed: one of 94 (1.1%) pedicle screws misplaced, which did not require revision postoperatively; one of 23 patients (4.3%) with a pulmonary embolism and one of 23 (4.3%) patients with transient nerve root pain. There were no occurrences of infection and no postoperative cerebrospinal fluid leaks. We conclude that MI-TLIF offers patients a safe and effective surgical option for lumbar spondylolisthesis treatment. Furthermore, it may offer patients additional advantages in terms of postoperative pain and recovery.


Up-regulation of inflammatory reactions by MPT32, a secreted protein of Mycobacterium tuberculosis in RAW264.7 macrophages.
Tuberculosis (TB) is caused by Mycobacterium tuberculosis (Mtb) and is still one of the global health burdens. The occurrence of various cases and multidrug resistance confirm that TB has not been completely conquered. For these reasons, the present research has been conducted to explore TB vaccine and drug candidate possibility using Mtb-secreted proteins. Among these proteins, MPT32 is known to have antigenicity and immunogenicity. There has not been a report on the host immune responses and regulation in macrophage cells. The present study was conducted with MPT32 in RAW 264.7 murine macrophage cells that control immune responses by sensing pathogen invasion and environmental change. We have found that MPT32 could activate lipopolysaccharide (LPS)-induced gene expression of metalloproteinase-9 (MMP-9) and inflammation in RAW 264.7 cells. After treating cells with MPT32, the increase in pro-inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), interleukin (IL)-1β (IL-1β) and IL-6, was observed. In addition, activated macrophages expressed inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) to generate various inflammatory mediator molecules, such as nitric oxide (NO). The increase in iNOS and COX-2 levels, which are up-regulators of MMP-9 expression, was also confirmed. The biochemical events are involved in the downstream of activated MAPK signaling and translocation of NF-κ B transcription factor. The present results prove the immunomodulatory effect of MPT32 in the RAW 264.7 murine macrophage cells. it claims the possibility of a TB vaccination and drug candidate using MPT32, contributing to the prevention of TB.


Differential protein expression of hepatic cells associated with MeHg exposure: deepening into the molecular mechanisms of toxicity.
Understanding the molecular mechanisms underlying MeHg toxicity and the way in which this molecule interacts with living organisms is a critical point since MeHg represents a well-known risk to ecosystems and human health. We used a quantitative proteomic approach based on stable isotopic labeling by amino acids in cell culture in combination with SDS-PAGE and nanoflow LC-ESI-LTQ for analyzing the differential protein expression of hepatic cells associated to MeHg exposure. Seventy-eight proteins were found de-regulated by more than 1.5-fold. We identified a number of proteins involved in different essential biological processes including apoptosis, mitochondrial dysfunction, cellular trafficking and energy production. Among these proteins, we found several molecules whose de-regulation has been already related to MeHg exposure, thus confirming the usefulness of our discovery approach, and new ones that helped to gain a deeper insight into the biomolecular mechanisms related to MeHg-induced toxicity. Overexpression of several HSPs and the proteasome 26S subunit itself showed the proteasome system as a molecular target of toxic MeHg. As for the interaction networks, the top ranked was the nucleic acid metabolism, where many of the identified de-regulated proteins are involved.


Structural studies on the carbohydrate units of armadillo submandibular glycoprotein.
The structure of carbohydrate units of the major glycoprotein fraction of armadillo submandibular gland was investigated. Alkaline borohydride reductive cleavage of the glycoprotein resulted in the release of O-glycosidically linked mono- and disaccharide units. The monosaccharide was identified as N-acetylgalactosaminitol, whereas disaccharide contained of N-acetylneuraminic acid and N-acetylgalactosaminitol. Treatment of the native and desialyzed glycoprotein with alpha-N-acetylgalactosaminidase resulted in the removal of 60% and 96% of N-acetylgalactosamine, respectively. No cleavage of this sugar was affected by the action of beta-N-acetylhexosaminidase. Both N-acetylgalactosamine and N-acetylneuraminic acid were susceptible to oxidation with periodate. Analyses of the partially methylated N-acetylgalactosamine derivatives, obtained from the permethylated native glycoprotein, showed the presence of 3,4,6-tri-O-methyl-N-methylacetamidogalactose and 3,4-di-O-methyl-N-methylacetamidogalactose in a ratio of 1 : 0.4. Only 3,4,6-tri-O-methyl-N-methylacetamidogalactose was found in the hydrolysates of permethylated desialyzed glycoprotein. These results together with our previous data on chemical composition of the glycoprotein suggest that about 30% of the oligosaccharide chains consist of NeuAc alpha 2 leads to 6GalNAc alpha 1 leads to O-Thr(Ser) and 70% of GalNAc alpha leads to O-Thr(Ser).


A Comprehensive review on Pharmacokinetic Studies of Vaccines: Impact of delivery route, carrier-and its modulation on immune response.
The lack of knowledge about the absorption, distribution, metabolism, and excretion (ADME) of vaccines makes former biopharmaceutical optimization difficult. This was shown during the COVID-19 immunization campaign, where gradual booster doses were introduced.. Thus, understanding vaccine ADME and its effects on immunization effectiveness could result in a more logical vaccine design in terms of formulation, method of administration, and dosing regimens. Herein, we will cover the information available on vaccine pharmacokinetics, impacts of delivery routes and carriers on ADME, utilization and efficiency of nanoparticulate delivery vehicles, impact of dose level and dosing schedule on the therapeutic efficacy of vaccines, intracellular and endosomal trafficking and in vivo fate, perspective on DNA and mRNA vaccines, new generation sequencing and mathematical models to improve cancer vaccination and pharmacology, and the reported toxicological study of COVID-19 vaccines. Altogether, this review will enhance the reader's understanding of the pharmacokinetics of vaccines and methods that can be implied in delivery vehicle design to improve the absorption and distribution of immunizing agents and estimate the appropriate dose to achieve better immunogenic responses and prevent toxicities.


Mentorship ReSPeCT Study: A Nurse Mentorship Program's Impact on Transition to Practice and Decision to Remain in Nursing for Newly Graduated Nurses.
The COVID-19 pandemic has worsened a pre-existing US nursing shortage, leaving newly graduated nurses vulnerable in their early career. This study analyzed the effectiveness of a mentorship program offering individualized mentorship through culturally congruent, customized pairing for 96 mentees. Key findings of this study show that this nursing mentorship was beneficial for the majority of mentees on their decision to remain in nursing, and on their self-confidence, problem-solving, professional communication, and transition to practice, with perceived benefits steadily increasing for mentees up to 2 years. These findings have valuable implications for innovative recruitment and retention interventions to address the nursing shortage.


How Transcranial Doppler can assess the effect of hyperosmolar therapy and the degree of circulatory compromise in acute brain herniation.
Patients in acute neurological extremes secondary to refractory intracranial hypertension are challenging because of the complex management options available to them, especially when compounded with signs of brainstem compromise. Objective evidence of cerebral circulatory compromise is often lacking. We present a case in which an objective evaluation of a cerebral circulatory compromise was documented using transcranial Doppler as well as its resolution with hyperosmolar therapy.


Basic fibroblast growth factor fused to a signal peptide transforms cells.
Basic fibroblast growth factor (bFGF) is a potent growth and angiogenic factor that is found in abundance in tissues such as brain, hypothalamus, kidney and cartilage. Despite this copious production of bFGF, most of these tissues are not undergoing either active growth or angiogenesis, suggesting that bFGF activity must be regulated so as to prevent autostimulation of cell growth. In cultured cells, bFGF is associated mainly with cells and basement membranes and is not released into the medium. Prevention of release could be a mechanism for regulation of bFGF activity and may be a consequence of the apparent absence of a secretory-signal sequence in the bFGF protein. Here we investigate whether this regulation can be overridden through the forced secretion of bFGF. Such secretion might provide the bFGF access to its receptor and in turn lead to autocrine transformation of the cell. We report that bFGF, as specified by a recombinant plasmid, is itself unable to induce such transformation, but acquires this ability after fusion with a secretory-signal sequence. The resulting transformants undergo unusual morphological alteration and display tumorigenicity.


A comprehensive review of intelligent controlled release antimicrobial packaging in food preservation.
Intelligent responsive packaging provides informative feedback or control the release of active substances like antimicrobial agents in response to stimuli in food or the environment to ensure food safety. This paper provides an overview of two types of intelligent packaging, information-responsive and intelligent controlled-release, focusing on the recent research progress of intelligent controlled-release antimicrobial packaging with enzyme, pH, relative humidity, temperature, and light as triggering factors. It also summarizes the current status of application in different food categories, as well as the challenges and future prospects. Intelligent controlled-release technology aims to optimize the antimicrobial effect and ensure the quality of food products by synchronizing the release of active substances with food preservation needs through sensing stimuli, which is an innovative and challenging packaging technology. The paper seeks to provide a reference for the research and industrial development of responsive intelligent packaging and controlled-release packaging applications in food.


Combining immunoreactive trypsinogen and pancreatitis-associated protein assays, a method of newborn screening for cystic fibrosis that avoids DNA analysis.
To evaluate the performance of a strategy in which, after immunoreactive trypsinogen (IRT) determination, genetic analysis is replaced by a biological test, the pancreatitis-associated protein (PAP) enzyme-linked immunosorbent assay (ELISA). The French newborn screening program includes cystic fibrosis (CF) screening by the IRT/CFTR mutation strategy. PAP was assayed on screening cards, in parallel with IRT, in all newborns from 5 French regions (n = 204,749). Analysis of PAP values in CF and non-CF newborns with elevated IRT allowed direct comparison between the current strategy and the proposed IRT/PAP strategy. A protocol in which newborns with IRT >50 ng/mL and PAP >1.8 ng/mL and those with IRT >100 ng/mL and PAP >1.0 ng/mL are directly recalled for sweat testing would have the same performance as the IRT/CFTR mutation strategy. The IRT/PAP strategy is an alternative for CF newborn screening, which avoids the drawbacks of genetic analysis and is cheaper and easier to implement than the current IRT/CFTR mutation strategy.


The possible effect of silver nanoparticles on glyceraldehyde-3-phosphate dehydrogenase activity and formation of amyloid-like aggregates in MCF-7 cell line.
Silver nanoparticles (AgNPs) are widely used in medicine, however, the underlying mechanisms of their action on cellular signaling have not been completely determined, and fundamental studies are required to clarify them. We aimed to investigate AgNPs effects on glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as both the internal control gene and the redox-sensitive enzyme involved in apoptosis-related pathways and the formation of amyloid aggregates. To achieve this purpose, MCF-7 cells were treated with different concentrations (0, 3, 22, and 200 μg/ml) of AgNPs and then cell viability, generation of reactive oxygen species (ROS), induction of apoptosis, expression of GAPDH gene, the formation of amyloid aggregates, and GAPDH activity were assessed. The results indicated that treatment with AgNPs significantly reduced cell viability and increased apoptosis in a dose-dependent manner. The ROS levels increased at lower concentrations of AgNPs (up to 22 μg/ml) and during short-term exposure (30 min). The level of GAPDH gene expression was significantly upregulated by 1.22, 1.47, and 1.56 fold, in the concentrations of 3, 22, and 200 μg/ml, respectively. The amount of amyloid aggregates was significantly increased in a dose-dependent manner. The results of enzyme activity showed that AgNPs were affected on the activity of GAPDH protein, however, it has fluctuated that could not be interpreted by our limited data. In conclusion, our results suggested that AgNPs could affect the GAPDH gene expression and enzyme activity, therefore the selection of GAPDH as a gene and protein internal control in the (AgNPs)-related studies requires careful consideration. Additionally, AgNPs may cause apoptosis due to the increase in the production of amyloid aggregates.


Characterization of the mechanical properties of tough biopolymer fibres from the mussel byssus of Aulacomya ater.
Byssus fibres are tough biopolymer fibres produced by mussels to attach themselves to rocks. In this communication, we present the mechanical properties of the byssus from the South American mussel Aulacomya ater which have not been previously reported in the literature. The mechanical properties of the whole threads were assessed by uniaxial tensile tests of dry and hydrated specimens. Elastoplastic and elastomeric stress-strain curves were found for byssal threads from A. ater in the dry and hydrated state, respectively. The results obtained from mechanical tests were modelled using linear, power-law-type and Mooney-Rivlin relationships. These methods for dealing with tensile measurements of mussel byssus have the potential to be used with other stretchy biomaterials.


Operational-modes of field-flow fractionation in microfluidic channels.
Through a careful consideration of the retention ratio for field-flow fractionation (FFF), we show that a single unified ideal retention theory can predict a wide range of separation behaviours including hydrodynamic chromatography, normal-mode FFF and steric-mode FFF by introducing the concept of a device retention parameter. We determine the critical device retention parameter above which normal-mode does not exist and there is no clear distinction between hydrodynamic chromatography and steric-mode FFF. Numerical analysis of the elution order as a function of particle size quantitatively predicts the transitions between these regimes. The resulting map of the operational-modes shows each of the regions and their connectivity, and so may guide future device design. By extending this analysis to account for the variation of stress over particle surfaces, a hitherto unreported regime called Faxén-mode FFF is predicted, which has the same elution order as normal-mode FFF. This mode arises when particle sizes approach the channel height, as can occur when microfluidic devices are utilized for FFF. The transition from steric-mode to Faxén-mode FFF is numerically mapped and approximations for each transition are presented.


Longitudinal changes of endocrine and bone disease in adults with β-thalassemia major receiving different iron chelators over 5 years.
In this study, we compared the long-term effects of different iron chelation regimens (deferoxamine, deferiprone, deferoxamine + deferiprone, and deferasirox) in preventing or reversing endocrinopathy (diabetes mellitus, hypothyroidism, or hypogonadism) and bone disease (measured through DEXA) in 165 adults with β-thalassemia major (TM) (mean age 39.9 ± 8.3 years, 43 % males). After five consecutive years of therapy, patients on deferasirox had the highest decrease in the prevalence of any endocrinopathy compared to other chelators which either had no change (deferiprone and deferoxamine) or had an increase (deferoxamine + deferiprone), p = 0.015. This was attributed to a lower proportion of patients on deferasirox developing new-onset endocrinopathy and higher proportion showing reversal of disease, compared to other chelators. A serum ferritin level of >1300 ng/mL predicted the development of new endocrinopathy (p = 0.025) while a level of <200 ng/mL predicted reversal of existing endocrinopathy (p = 0.147). A significant increase in mean BMD T-score (p < 0.001) and a considerable decrease in osteoporosis prevalence were observed in patients receiving deferasirox but not other chelators. Iron chelation therapy with deferasirox has a role in the prevention of endocrinopathy and reversal of existing disease.


Toward an integrated theory of adolescent ego development: the "new look" at adolescent egocentrism.
The theoretical and empirical status of the traditional theory of adolescent egocentrism is examined and found wanting. An alternative theory is reviewed that reconceptualizes the ideational patterns of "egocentrism" as adaptational and coping functions of ego development, avoids anomalies found in the traditional theory, and promises a progressive research program.


Identifying an ovarian cancer cell hierarchy regulated by bone morphogenetic protein 2.
Whether human cancer follows a hierarchical or stochastic model of differentiation is controversial. Furthermore, the factors that regulate cancer stem-like cell (CSC) differentiation potential are largely unknown. We used a novel microfluidic single-cell culture method to directly observe the differentiation capacity of four heterogeneous ovarian cancer cell populations defined by the expression of the CSC markers aldehyde dehydrogenase (ALDH) and CD133. We evaluated 3,692 progeny from 2,833 cells. We found that only ALDH(+)CD133(+) cells could generate all four ALDH(+/-)CD133(+/-) cell populations and identified a clear branched differentiation hierarchy. We also observed a single putative stochastic event. Within the hierarchy of cells, bone morphologenetic protein 2 (BMP2) is preferentially expressed in ALDH(-)CD133(-) cells. BMP2 promotes ALDH(+)CD133(+) cell expansion while suppressing the proliferation of ALDH(-)CD133(-) cells. As such, BMP2 suppressed bulk cancer cell growth in vitro but increased tumor initiation rates, tumor growth, and chemotherapy resistance in vivo whereas BMP2 knockdown reduced CSC numbers, in vivo growth, and chemoresistance. These data suggest a hierarchical differentiation pattern in which BMP2 acts as a feedback mechanism promoting ovarian CSC expansion and suppressing progenitor proliferation. These results explain why BMP2 suppresses growth in vitro and promotes growth in vivo. Together, our results support BMP2 as a therapeutic target in ovarian cancer.


Fat mass is an important predictor of parathyroid hormone levels in postmenopausal women.
Previously, we reported that people with elevated parathyroid hormone (PTH) levels due to primary hyperparathyroidism have increased body weight compared to eucalcemic controls. We sought to determine whether the same relationship between PTH and body weight exists in eucalcemic healthy postmenopausal women, and to investigate the relationships between components of body weight, PTH, vitamin D metabolites, and metabolic indices. We performed a cross-sectional analysis of 116 healthy community-dwelling postmenopausal women. Pearson correlation analysis was used to test for univariate linear relationships between variables, and stepwise multiple regression analysis to assess for multivariate relationships. We found that PTH was significantly positively correlated with body weight, regional and total fat mass, and percent body fat, and negatively correlated with activity levels, 25 hydroxyvitamin D (25OHD), dietary calcium intake, and serum phosphate. On multivariate analysis, PTH was positively related to percent body fat (P = 0.020; partial r2 = 0.10) and negatively related to dietary calcium intake (P = 0.041; partial r2 = 0.03) and serum phosphate (P = 0.026; partial r2 = 0.04). Adjusting for vitamin D insufficiency or 25OHD levels did not affect the relationship between PTH and fat mass. For 25OHD, there were significant positive correlations with lumbar spine BMD and serum albumin, and significant negative correlations with PTH, total fat mass, trunk fat, and pelvic fat. On multivariate analysis, 25OHD was positively related to serum albumin (P = 0.008; partial r2 = 0.07) and negatively related to pelvic fat mass (P = 0.014; partial r2 = 0.05). Adjusting for PTH levels did not change the relationship between 25OHD and pelvic fat mass. We conclude that fat mass is a significant independent determinant of serum PTH levels, and that this relationship is independent of the inverse relationship between 25OHD and fat mass. This association between fat mass and PTH might contribute to the association between primary hyperparathyroidism and increased body weight.


Bioluminescence Imaging, a Powerful Tool to Assess Fungal Burden in Live Mouse Models of Infection.
Aspergillus fumigatus and Cryptococcus neoformans species infections are two of the most common life-threatening fungal infections in the immunocompromised population. Acute invasive pulmonary aspergillosis (IPA) and meningeal cryptococcosis are the most severe forms affecting patients with elevated associated mortality rates despite current treatments. As many unanswered questions remain concerning these fungal infections, additional research is greatly needed not only in clinical scenarios but also under controlled preclinical experimental settings to increase our understanding concerning their virulence, host-pathogen interactions, infection development, and treatments. Preclinical animal models are powerful tools to gain more insight into some of these needs. However, assessment of disease severity and fungal burden in mouse models of infection are often limited to less sensitive, single-time, invasive, and variability-prone techniques such as colony-forming unit counting. These issues can be overcome by in vivo bioluminescence imaging (BLI). BLI is a noninvasive tool that provides longitudinal dynamic visual and quantitative information on the fungal burden from the onset of infection and potential dissemination to different organs throughout the development of disease in individual animals. Hereby, we describe an entire experimental pipeline from mouse infection to BLI acquisition and quantification, readily available to researchers to provide a noninvasive, longitudinal readout of fungal burden and dissemination throughout the course of infection development, which can be applied for preclinical studies into pathophysiology and treatment of IPA and cryptococcosis in vivo.


Comparative evaluation of [(99m)tc]tilmanocept for sentinel lymph node mapping in breast cancer patients: results of two phase 3 trials.
Sentinel lymph node (SLN) surgery is used worldwide for staging breast cancer patients and helps limit axillary lymph node dissection. [(99m)Tc]Tilmanocept is a novel receptor-targeted radiopharmaceutical evaluated in 2 open-label, nonrandomized, within-patient, phase 3 trials designed to assess the lymphatic mapping performance. A total of 13 centers contributed 148 patients with breast cancer. Each patient received [(99m)Tc]tilmanocept and vital blue dye (VBD). Lymph nodes identified intraoperatively as radioactive and/or blue stained were excised and histologically examined. The primary endpoint, concordance (lower boundary set point at 90 %), was the proportion of nodes detected by VBD and [(99m)Tc]tilmanocept. A total of 13 centers contributed 148 patients who were injected with both agents. Intraoperatively, 207 of 209 nodes detected by VBD were also detected by [(99m)Tc]tilmanocept for a concordance rate of 99.04 % (p < 0.0001). [(99m)Tc]tilmanocept detected a total of 320 nodes, of which 207 (64.7 %) were detected by VBD. [(99m)Tc]Tilmanocept detected at least 1 SLN in more patients (146) than did VBD (131, p < 0.0001). In 129 of 131 patients with ≥1 blue node, all blue nodes were radioactive. Of 33 pathology-positive nodes (18.2 % patient pathology rate), [(99m)Tc]tilmanocept detected 31 of 33, whereas VBD detected only 25 of 33 (p = 0.0312). No pathology-positive SLNs were detected exclusively by VBD. No serious adverse events were attributed to [(99m)Tc]tilmanocept. [(99m)Tc]Tilmanocept demonstrated success in detecting a SLN while meeting the primary endpoint. Interestingly, [(99m)Tc]tilmanocept was additionally noted to identify more SLNs in more patients. This localization represented a higher number of metastatic breast cancer lymph nodes than that of VBD.


Pharmacokinetics and tolerability of intravenous rizatriptan in healthy females.
The pharmacokinetics and tolerability of intravenous (i.v.) rizatriptan (MK-0462), a novel 5-HT1D/1B receptor agonist for the acute oral treatment of migraine, were examined in an open, single-dose, four-period, randomized crossover study in healthy females. Results of this study indicated that i.v. rizatriptan (0.5-5 mg) was well tolerated. The disposition kinetics of rizatriptan were linear for i.v. doses up to and including 2.5 mg. Relative to the 0.5 mg dose, geometric mean dose-adjusted AUC ratios were 1.04, 1.09, and 1.18 for 1, 2.5, and 5 mg doses, respectively. Apparent plasma clearance (Cl) ranged between 859 and 941 mL min(-1) from 0.5 to 2.5 mg, but dropped to slightly below 800 mL min(-1) for the 5 mg dose. Therefore, the elimination of rizatriptan appears somewhat dose dependent at the high end of this dose range. Mean plasma half-life (t1/2) was 1.5-2.2 h across all doses while mean residence time in the body (MRT) and steady state volume of distribution (Vss) of rizatriptan remained relatively invariant across doses. Urinary excretion of rizatriptan (Ue) ranged from 14.5 to 34.6% of dose.


Pancreatic ductal anatomy: more than meets the eye.
Anatomical variations of the pancreas are relatively frequent and often understudied. The ductal system of the pancreas has multiple variations, which are not frequently reported in the literature. The anatomy of the pancreas was studied through macroscopic anatomical dissection on 50 organ complexes (the pancreas, spleen, and duodenum) donated to the department of human anatomy, from patients, who died of causes not related to pancreatic diseases. In type I, the main pancreatic duct (Wirsung's duct, MPD) and the accessory pancreatic duct (Santorini's duct, APD) were merged but most of the head was drained by the MPD (10% of cases). In type II, the MPD and APD were merged but most of the head was drained by the APD (4% of cases). In type III, the APD was absent and the head was drained by the MPD (14% of cases). In type IV, there was an inverted pancreas divisum where the ducts did not merge but each drained a part of the head (6% of cases). Classical pancreas divisum where the ducts did not merge but each drained a part of the head was considered as type V (4% of cases). In type VI, the MPD and APD merged and each drained a part of the head (48% of cases). In type VII, the MPD and APD merged but the upper part of the head was drained by the main pancreatic duct (4% of cases). In type VIII, the MPD and APD merged but the lower part of the head was drained by the main pancreatic duct (4% of cases). In the IX type, the MPD and APD merged but the head was drained by the branches of the MPD (6% of cases). There are several drainage patterns of the pancreas. In some cases, one of the ducts provides more drainage of the gland than the other. This is clinically relevant since blockage of the main source of drainage leads to pancreatic juice stasis. It also explains cases when partial or total blockage of the duct results in the pancreatitis of an isolated zone.


Perception of action boundaries in patients with frontal lobe damage.
The prefrontal cortex is known to be involved in action planning and in controlling behaviour. Neuropsychological evidence also supports the idea that the prefrontal cortex is generally involved in processing complex events, such as action knowledge. Actions are represented in memory as sequences of goal-directed discrete events. Complex events can be divided into discrete smaller units and organised in a hierarchical manner. The aim of the present study was to investigate the ability of 9 patients with prefrontal lesion and 12 healthy controls to parse action sequences into meaningful events. Subjects were requested to detect the transitions between events under three different orientation instructions: (1) spontaneous; (2) small events; and (3) large event. Both normal subjects and patients identified significantly more events under the small-oriented condition. However, contrary to normal controls (NCs), patients with prefrontal damage showed considerable difficulties in detecting large event units than small event units. These results strongly suggest that prefrontal cortex is specifically involved in parsing and recognising clusters of action sequences. These findings also show that the way in which instructions orient subjects' attention, has an effect on how action information is encoded and represented in memory.


Ozone weekend effect in Santiago, Chile.
The study examined weekday-weekend differences in ozone, NO(x) (NO and NO(2)) and VOC concentrations in Santiago, Chile, from 1999 to 2007. The results provide evidence for the occurrence of an atmospheric phenomenon that produces higher ozone concentrations during weekends despite lower concentrations of ozone precursors. This phenomenon is known as the weekend effect (WE). The overall ozone decrease since the spring of 2004 was a consequence of the implementation of several urban pollution control measures. Although these measures caused a decline in the number of days that exceed the national standard from two-thirds to one-third of summer days, the WE, which became statistically significant beginning in September 2004, could not be eliminated. Furthermore, VOC/NO(x) ratios decreased during the same period (2004), especially in the most industrialized area of Santiago. Similarly, under these regimes, the VOC/NO(x) ratios were higher on Sundays than on weekdays and caused higher ozone concentrations on Sundays.


Tillage, crop rotation, and organic amendment effect on changes in soil organic matter.
Carbon sequestration in agricultural soils is controlled by the balance of added organic residues and microbial oxidation of both residues and native organic matter (OM) as moderated by management and tillage. The PC-based model CQESTR predicts decomposition of residues, organic amendments and soil OM, based on cropping practices. CQESTR uses RUSLE (Revised Universal Soil Loss Equation) crop rotation and management practice, crop production, and operation databases. These data are supplemented with residue nitrogen and soil OM, bulk density, and layer thickness. CQESTR was calibrated with soil carbon data from 70-year-long experiments at the Research Center at Pendleton, OR. The calibrated model provides estimates with a 95% confidence interval of 0.33% OM. Validation at 11 independent sites resulted in a matching of observed with calculated OM with a 95% confidence interval of 0.55% OM. A 12th site, with a history of severe erosion, provided a poor match.


Efficacy of Valproic Acid Against Coronavirus Disease 2019 Infection or Severity: A Pilot Study.
The purpose of the current study was to investigate whether taking valproic acid (VPA) was protective against coronavirus disease 2019 (COVID-19) infection or severity in patients with epilepsy. This was a questionnaire study of 150 people who were taking VPA in monotherapy or polytherapy (since the start of the pandemic or longer) and also 150 people who were not taking VPA (since the start of the pandemic), registered in our epilepsy database. The data compared rates of the seropositivity and severity of infection of COVID-19 between the 2 groups. The latter was assessed, by proxy, vis-à-vis rates of hospital admission and intensive care unit admission. Two hundred forty-one patients were studied, including 130 (53.9%) male and 111 (46.1%) female patients. The mean age of the patients was 30.7 ± 11.4 years. The infection rate and severity of COVID-19 did not significantly differ among patients who were taking VPA and those who were not taking VPA (P = 0.587) and (P = 0.648), respectively. In this pilot study, no support was found for the hypothesis of a protective effect of VPA against the infectivity rate of COVID-19. Neither was there any indication of a disease-modulating effect of VPA in people with active COVID-19 infection. Larger, randomized controlled trials would be warranted to substantiate our conclusion.


Estrogen modulated gonadotropin release in relation to gonadotropin-releasing-hormone (GnRH) and phorbol ester (PMA) actions in superfused rat pituitary cells.
The involvement of protein kinase C (PKC) in GnRH action is still a matter of controversy. We have conducted a comparative study of LH and FSH release in response to GnRH and to phorbol ester myristate acetate (PMA), an activator of PKC, by rat pituitary cells maintained in culture. The effect of E2 pretreatment coupled or not with PKC depletion was also studied. Different kinetics in the response of LH and FSH to GnRH were observed, suggesting that the intracellular pathways involved in the release process of the two hormones were somewhat different. Moreover, PMA (10 nM) stimulated LH release greatly and FSH release only slightly. Intracellular PKC depletion, obtained by a prolonged treatment (18 h) of the cells with PMA (1 microM), produced different results according to the endocrine status of the pituitary cells. GnRH (10 nM)-induced LH release was significantly decreased in PKC-depleted cells from proestrous females. For PKC-depleted cells from OVX females, it was decreased significantly only when cells had been pretreated by E2. These results suggest that the modulation of LH secretion by E2 involves PKC activation. FSH release was poorly stimulated by PMA; but, under any conditions, PKC depletion did not affect GnRH-induced FSH release.