Technology-enhanced in vivo exposures in Prolonged Exposure for PTSD: A pilot randomized controlled trial.
In vivo exposures (IVEs) are a key component of exposure-based treatments, during which patients approach fear-provoking, yet safe, situations in "real life." This pilot study assessed the use of a wearable technology (Bio Ware) during IVEs to enhance Prolonged Exposure (PE) therapy for PTSD. Bio Ware provides a clinician dashboard with real-time physiological and subjective data for clinicians to use for virtually guided IVEs. Participants (N = 40) were randomized to a Guided group that received standard PE and virtual, clinician-guided IVEs with the Bio Ware device, or a Non-Guided group that received standard PE and used the Bio Ware device on their own for IVEs. Multilevel linear models with bootstrapping were completed on the intent-to-treat (ITT; N = 39) and per-protocol samples (PP; n = 23), defined as completing at least eight sessions of PE and using the Bio Ware system during ≥ 1 IVEs. In the PP sample, there were significant effects of treatment condition (b = -14.55, SE = 1.47, 95% CI [-17.58, -11.78], p < .001) and time (b = -1.98, SE = 0.25, 95% CI [-2.47, -1.48], p < .001). While both groups showed reductions in PTSD symptoms, the Guided group evidenced significantly greater reductions than the Non-Guided group. These findings demonstrate the feasibility and safety of leveraging Bio Ware for virtual, clinician-guided IVEs during PE therapy for PTSD and suggest that virtual, clinician-guided exposures may enhance treatment outcomes. CLINICAL TRIAL REGISTRATION: NCT04471207.


Surgical treatment of achilles tendon rupture: examination of strength of 3 types of suture techniques in a cadaver model.
The mechanical properties of present-day percutaneous repairs of Achilles tendon ruptures are not known. Artificially-created ruptures in 24 human cadaveric Achilles tendons were repaired with an open Bunnell repair, a percutaneous calcaneal tunnel or a percutaneous bone-anchor repair. In the open technique no.1 PDS-II absorbable suture material was used, and in the percutaneous techniques either no.1 PDS-II or no.1 Panacryl absorbable suture material was used. The specimens were tested in a materials testing machine until failure occurred. The common mode of failure was suture breakage in non-anchor repairs, and anchor pullout in anchor repairs. The average strength of the repairs varied from 166 N (SD 60) to 211 N (SD 30), with no differences between the techniques (p = 0.5). Taking costs into account, the percutaneous calcaneal tunnel technique and the open technique are the methods of choice.


Nitric oxide activated by p38 and NF-kappaB facilitates apoptosis and cell cycle arrest under oxidative stress in evodiamine-treated human melanoma A375-S2 cells.
Nitric oxide (NO) has been identified as a fundamental molecule that interplays with reactive oxygen species (ROS) in determining cell fate. As a previous study indicated that ROS was stimulated in evodiamine-induced human melanoma A375-S2 cell apoptosis, the goal of this study was to investigate the role of NO in the cells. In this study, it was found that evodiamine has a strong inductive effect on NO production synthesized by inducible NOS (iNOS) enzyme in a positive-feedback manner. The generated NO was further showed to induce apoptosis and cell cycle arrest and linked to the activation of p53 and p21. After interruption of p38 and nuclear factor-kappaB (NF-kappaB) by pre-treatment with SB203580 and PDTC, iNOS expression, NO synthesis and cell damage were all significantly blocked. It was concluded that p38 and NF-kappaB were critical to the NO producing system, which contributed greatly to the apoptosis and cell cycle arrest in evodiamine-incubated cells.


The human sex ratio: increase in first-born males to parents with shared HLA-DR antigens.
Maternal-fetal HLA-DR antigen sharing has been reported to affect the sex ratio of first-born. We therefore studied offspring sex ratios and birth orders in 66 families in which parents shared one or more HLA-DR antigens as compared to 61 families with no parental HLA-DR sharing. A significant excess of males was found among first-born children who were HLA-DR compatible with their mothers compared to first-born HLA-DR incompatible children of couples sharing HLA-DR antigens and couples not sharing HLA-DR antigens. Increased numbers of males may persist among children of higher birth orders in families where parents share both HLA-DR antigens, but not among couples sharing only one HLA-DR antigen. We hypothesize that the presence of the H-Y antigen in the male fetus may provide the necessary stimulus for a successful pregnancy in HLA-DR compatible pregnancies and may explain the excess of male births in the general population.


Phosphatidylinositide 3-kinase activity is required for stabilin-1-mediated endosomal transport of acLDL.
Stabilin-1 is a type 1 transmembrane receptor specifically expressed by tissue macrophages and sinusoidal endothelial cells. We recently demonstrated that stabilin-1 is involved in the endocytic/recycling pathway and shuttles between the endosomal system and the trans-Golgi network (TGN) in human macrophages. In the present study, we designed a model cell system to study the mechanisms of stabilin-1-mediated endocytosis. Using CHO-K1 cells stably transfected with stabilin-1, we demonstrated that acetylated low-density lipoprotein (acLDL) induces recruitment of stabilin-1 into the endocytic pathway. Stabilin-1 mediates internalisation of acLDL and its delivery to early endosomes, and it is translocated together with its ligand to the late endosomal compartment. Treatment with wortmannin, a specific inhibitor of phosphatidylinositide 3-kinase (PI3K), did not block stabilin-1 mediated internalisation of acLDL as well as its trafficking to early endosomes, whereas it induced enlargement of stabilin-1/acLDL positive endosomes as well as partial dissociation of EEA1 from these structures. The major effect of wortmannin was the abrogation of stabilin-1/acLDL trafficking into the late endocytic pathway. In stabilin-1 positive human type 2 macrophages, wortmannin treatment resulted in formation of both enlarged and small stabilin-1 positive endosomes. This effect, however, was significantly weaker in macrophages as compared to CHO-stabilin-1 cells. Our data indicate that PI3K activity is required for the transfer of stabilin-1 and its ligand acLDL from early to late endosomal compartments.


Determination of multiple organic flame retardants in maricultural water using High-volume/High-throughput Solid-phase extraction followed by liquid/gas chromatography tandem mass spectrometry.
A rapid and efficient analytical method is proposed and optimized for the enrichment, extraction and instrument analysis of four typical organic flame retardants (OFRs), including organophosphate esters (OPEs), polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDs) and dechlorane compounds (Dechloranes) in maricultural waters using High-volume/High-throughput Solid-phase extraction with in-situ ultrasonic technique followed by high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) and gas chromatography tandem mass spectrometry (GC-MS) instrumental detection. The optimized pretreatment conditions were that the analytes were enriched by XAD-2 resins and eluted repeatedly with 50 mL hexane/acetone (1:1, v:v) for 5 min. The results of method validation exhibited that the developed method can be used for quantitative detection of 11 OPEs, 13 PBDEs, 3 HBCDs and 5 Dechloranes in water samples. The method detection limits (MDLs) and limits of quantification (LOQs) are 0.4-26.2 pg/L and 1.5-87.4 pg/L for OPEs, 23.3-35.4 pg/L and 77.5-117.9 pg/L for HBCDs, 0.8-97.4 pg/L and 2.6-324.7 pg/L for PBDEs and 9.3-78.5 pg/L and 31.0-261.8 pg/L for Dechloranes, respectively. The method was successfully applied in lagoon maricultural areas in Hainan province, and the results showed that 4 OFRs were detected in almost all water samples. Total concentrations of 18 water samples were 1.89-39.97 ng/L for OPEs, 0.18-5.40 ng/L for PBDEs, ND-0.24 ng/L for HBCDs and 0.01-1.77 ng/L for Dechloranes, respectively. The optimized analytical method is highly sensitive and efficient with expectation to play an essential role in monitoring the ultra-trace organic pollutants and providing an effective risk assessment in ecological environment.


Calcium currents of rhythmic neurons recorded in the isolated respiratory network of neonatal mice.
To obtain a quantitative characterization of voltage-activated calcium currents in respiratory neurons, we performed voltage-clamp recordings in the transverse brainstem slice of mice from neurons located within the ventral respiratory group. It is assumed that this medullary region contains the neuronal network responsible for generating the respiratory rhythm. This study represents one of the first attempts to analyze quantitatively the currents in respiratory neurons. The inward calcium currents of VRG neurons consisted of two components: a high voltage-activated (HVA) and a low voltage-activated (LVA) calcium current. The activation threshold of the HVA current was at -40 mV. It was fully activated (peak voltage) between -10 and 0 mV. The half-maximal activation (V50) was at -27. 29 mV +/- 1.15 (n = 24). The HVA current was inactivated completely at a holding potential of -35 mV and fully deinactivated at a holding potential of -65 mV (V50, -52.26 mV +/- 0.27; n = 18). The threshold for the activation of the LVA current was at -65 mV. This current had its peak voltage between -50 and -40 mV (mean, V50 = -59. 15 mV +/- 0.21; n = 15). The LVA current was inactivated completely at a holding potential of -65 mV and deinactivated fully at a holding potential of -95 mV (mean, V50 = -82.40 mV +/- 0.32; n = 38). These properties are consistent with other studies suggesting that the LVA current is a T-type current. The properties of these inward currents are discussed with respect to their role in generating Ca2+ potentials that may contribute to the generation of the mammalian respiratory rhythm.


Uncovering factors influencing railway passenger experiences through love and breakup declarations.
While existing approaches for assessing passenger experience are often limited to surveys of customer satisfaction, societal and technological challenges push the railway industry to adopt a user-centric approach to the design of their service. We used the love and breakup method in a study involving N = 53 passengers making a declaration to their railway company to collect qualitative feedback on the passenger experience. The method allowed to gather personal, emotional, and contextual insights into passengers' experiences that can inform the transportation service design process. We describe 21 factors and 8 needs influencing the passenger experience, thereby consolidating and deepening prior work in the railway context. Using the lens of user experience theories, we argue that the service should be assessed against fulfilling these needs, which can act as guiding principles regarding service improvement. The study also presents valuable insights into the love and breakup method to explore service experiences.


N-Doped Carbon Quantum Dot (NCQD)-Deposited Carbon Capsules for Synergistic Fluorescence Imaging and Photothermal Therapy of Oral Cancer.
Use of nanomaterials blessed with both therapeutic and diagnostic properties is a proficient strategy in the treatment of cancer in its early stage. In this context, our paper reports the synthesis of uniform size N-rich mesoporous carbon nanospheres of size 65-70 nm from pyrrole and aniline precursors using Triton-X as a structure-directing agent. Transmission electron microscopy reveals that these carbons spheres contain void spaces in which ultrasmall nitrogen-doped quantum dots (NCQD) are captured within the matrix. These mesoporous hollow NCQD captured carbon spheres (NCQD-HCS) show fluorescence quantum yield up to 14.6% under λex = 340 nm. Interestingly, samples calcined at >800 °C clearly absorb in the wavelength range 700-1000 nm and shows light-to-heat conversion efficiency up to 52%. In vitro experiments in human oral cancer cells (FaDu) show that NCQD-HCS are internalized by the cells and induce a substantial thermal ablation effect in FaDu cells when exposed under a 980 nm near-infrared laser.


Effects of re-augmenting maintenance immunosuppression on post-transplant donor-specific HLA antibodies in liver transplantation.
Donor-specific antibodies (DSAs) have various negative short- and long-term effects after organ transplantation. DSAs are prevalent in patients with insufficient immunosuppression; thus, even patients with stable conditions after liver transplantation should be under optimized immunosuppression. However, the effect of re-augmenting immunosuppression therapy for patients with insufficient immunosuppression remains unclear. In this study, we investigated the long-term changes and the effects of immunosuppression (IS) re-augmentation on the DSA status. Two DSA screenings were performed in 67 patients during long-term follow-up after liver transplantation. After the first screening, IS re-augmentation was performed in patients with consent. The effects of IS re-augmentation on the DSA status were analyzed using data of the serial DSA screenings. Negative conversion was defined as DSA positivity with MFI > 1000 converted to MFI < 1000. Improvement of DSA status was defined as either a 50% reduction of MFI or negative conversion. The median interval between the first and second DSA screening was 50 months. Among 67 patients, 43 were positive for DSAs on the first screening. Among these 43 patients, 30 had minimal to no IS therapy at the time of the first screening. Among the 30 patients, IS re-augmentation was conducted in 19. A comparison between the patients with a re-augmented IS and those with a sustained minimized IS showed that the DSA levels significantly decreased in the former (63% (12/19) vs. 18% (2/11), p = 0.02). The results of this study indicate that post-liver transplant IS re-augmentation had suppressive effects on the DSA status. However, the clinical significance of DSA-negative conversion and/or mean fluorescence intensity reduction needs to be further investigated through histological evaluation and/or graft survival during longer follow-up periods.


Retrospective and prospective study of progressive retinal atrophy in dogs presented to the veterinary hospital of the Federal University of Parana, Brazil.
Progressive retinal atrophy (PRA) is one of the main causes of blindness in dogs. Despite its clinical importance, there is limited epidemiological information available, particularly in South America. The main objective of this study was to perform a retrospective, and prospective analysis of PRA in dogs admitted at the Veterinary Hospital of the Federal University of Paraná, Brazil. Medical records of dogs admitted between 2014 and 2018 were selected through the archives of the Comparative Ophthalmology Laboratory. A total of 130 dogs with medical records indicating clinical signs suggestive of PRA, independent of the electroretinography confirmation, were selected. In order to investigate common characteristics, each patient's clinical history, ophthalmic examination, and visual status were reviewed (obstacle course, pupillary light reflex, dazzle reflex, visual tracking to a cotton ball, and menace responses). Additionally, a prospective study was performed, where flash electroretinography was performed on 30 animals with clinical signs suggestive of PRA, and 14 animals were selected for fundus photography. Data were assessed through descriptive and inferential statistics. A total of 2,055 dogs were evaluated between January 2014 and December 2018. Of those, 130 animals were presumptively diagnosed with PRA (6.33%), consisting of 18 different breeds and 27 dogs with a mixed pedigree. Poodles were the most prevalent breed (n = 26; 20.00%), followed by Cocker Spaniels (n = 19; 14.62%). In the reported caseload, Pomeranians showed a considerably higher odds ratio for PRA development (15.36%). Pomeranians presented a high odds ratio, suggesting that further studies may be performed with breeds with a high potential for developing this disease.


Acute airway obstruction: a complication of aluminum tape wrapping of tracheal tubes in laser surgery.
A case is reported of acute airway obstruction arising from the use of a tracheal tube wrapped with aluminum tape during laryngeal surgery with a carbon dioxide laser. Problems associated with aluminum tape wrapping of tracheal tubes are discussed.


Clinicopathological study of a dimorphic variant of breast carcinoma.
Dimorphic cells have abundant clear cytoplasm similar to myoepithelial cells, and the nuclei are identical to those in adjacent malignant columnar epithelial cells. A dimorphic variant of a breast carcinoma involves a neoplastic proliferation of epithelial cells including dimorphic cells. The subjects were patients with primary breast carcinoma, who underwent surgical resection at the Hospital of Dokkyo Medical University between 2000 and 2016, and were reviewed and diagnosed with a dimorphic variant of breast carcinoma. Dimorphic ICs typically showed a low-grade tumor and Hormonal receptor (HR) (estrogen and/or progesterone)+/HER2- subtype. Age, mean tumor size, status of nodal metastasis, stage and disease-free survival and overall survival did not differ between dimorphic and non-dimorphic ICs. The dimorphic cells were negative for p63 and cytokeratin 5/6 and 14 in most cases. In contrast, dimorphic cells were positive for HR, androgen receptor, and showed marked membrane-associated staining for E-cadherin and cytoplasmic staining for gross cystic disease fluid protein 15. The morphological features of dimorphic cells may be confused with cells of other origins if the features of the dimorphic cells are not recognized. However, the typical morphological architecture of this carcinoma and expression of immunohistochemical markers support the diagnosis.


Prostaglandin release from macrophages: an assay system for anti-inflammatory drugs in vitro.
It is the intention of this communication to present a simple and reliable in vitro system for the evaluation of anti-inflammatory drugs. The system described appears to combine the advantages of two established procedures, i.e. measurement of the inhibition of prostaglandin (PG) synthesis in vitro using microsomal enzyme preparations and the measurement of the inhibitory effects of drugs on PG synthesis in vivo avoiding major limitations. We propose to measure the effect of drugs on the PG release from mouse peritoneal macrophages in vitro. The influence of culture conditions, phagocytosis and drugs on the PG release from these cells is described. We found that antibody-coated erythrocytes are especially suitable triggers of PG release, and that the release can be inhibited by steroidal and non-steroidal anti-inflammatory drugs in concentrations resembling their effective doses in vivo.


Sardines and other fried fish. The consumption of alcoholic beverages on a Micronesian island.
Drinking parties are an integral aspect of life on Etal Island, despite official sanctions against them. The parties help to preserve certain traditional community values and provide an outlet for tension caused by political and social change.


MiR-423-5p aggravates lung adenocarcinoma via targeting CADM1.
At present, microRNAs and its downstream genes have been regarded as influential indicators in various malignancies. Therefore, the aim of this study was to explore the relationship and molecular mechanism of the miR-423-5p and its downstream gene CADM1 in the LUAD. The pcDNA-CADM1 was used to construct the CADM1 overexpressed cell model. The cell proliferation was determined by CCK-8 and EdU assays and the cell metastasis was performed by wound scratch and transwell chamber assays. The relationship between miR-423-5p and CADM1 were determined by bioinformatics, luciferase reporter and western blot assays. The results revealed that the CADM1 was downregulated in LUAD tissues and cell lines. CADM1 overexpression markedly repressed the cell proliferation, migration and invasion. Moreover, the results of bioinformatics, luciferase reporter and WB assays showed that CADM1 was a target gene of miR-423-5p and the miR-423-5p expression was negatively associated with CADM1 in LUAD cell lines. Finally, rescue experiments revealed that downregulation of CADM1 could antagonize the functions of miR-423-5p inhibitor on cell proliferation and metastasis. These results indicated that miR-423-5p aggravated lung adenocarcinoma via downregulation of CADM1 expression. Downregulation of CADM1 could antagonize the functions of miR-423-5p inhibitor on cell proliferation and metastasis. miR-423-5p aggravated lung adenocarcinoma via downregulation of CADM1 expression.


Low-Density Lipoprotein Cholesterol and Risk of Hemorrhagic Stroke: a Systematic Review and Dose-Response Meta-analysis of Prospective Studies.
To systematically examine the association between low-density lipoprotein cholesterol (LDL-C) and risk of hemorrhagic stroke. A previous meta-analysis of prospective studies published in 2013 showed that higher concentrations of LDL-C were associated with lower risk of hemorrhagic stroke. Recently, seven large cohort studies were published examining LDL-C and risk of hemorrhagic stroke in different populations. Twelve prospective studies with 476,173 participants and 7587 hemorrhagic stroke cases were included in the current meta-analysis. The results showed that a 10 mg/dL increase in LDL-C was associated with 3% lower risk of hemorrhagic stroke (pooled relative risk [RR] 0.97, 95% confidence interval [CI] 0.95-0.98). The association appeared to be more pronounced in Asians (pooled RR 0.95, 95% CI 0.92-0.98), relative to Caucasians (pooled RR 0.98, 95% CI 0.97-1.00), with a p heterogeneity of 0.05 between two ethnic groups. Further genetic studies and clinical trials with a stricter safety monitoring strategy are warranted to understand the underlying pathogenesis and determine the treatment target of LDL-C range with the lowest risk of hemorrhagic stroke in different population groups.


Effects of age on brain oxidative metabolism in vivo.
Non-invasive optical techniques were used to monitor the effects of increasing cerebral energy demand on metabolic capabilities and vascular reactivity in young and aged brain. Low level of electrical stimulation of the cortex, in both young (4--7 months) and aged (24--28 months) rat brain, were accompanied by transient oxidations of NADH and cytochrome oxidase (a,a3) as measured by microfluorometry and reflection spectrophotometry respectively. Stimulation sufficient to produce spreading cortical depression was accompanied by an oxidation of both NADH and cytochrome a,a3 in young brain together with an increase in local blood volume. There was either no change or a slight disoxygenation of hemoglobin. In aged brain, however, spreading depression was associated with an oxidation of NADH and a reduction of cytochrome a,a3 together with an increase in local blood volume and an oxygenation of hemoglobin. The present results indicate that the relationship between microcirculation and the terminal oxidase step of the respiratory chain is altered in aged brain when energy demand is high.


The role of self-compassion in the relationship between hot flushes and night sweats and anxiety.
An association between hot flushes and night sweats (HFNS) and psychopathology, including depression, is well established for some women. However, the relationship between HFNS and anxiety needs further exploration. Self-compassion may be a psychosocial factor which influences the experience of HFNS and anxiety for midlife women. The aim of this study was to investigate the extent to which HFNS are associated with anxiety and examine the additional importance of self-compassion. A cross-sectional design using questionnaire data from 109 women aged 45-66 years was employed and multiple hierarchical regression was used to explore relationships between HFNS, anxiety and self-compassion. The results indicated that interference of HFNS in everyday life (β =.31), but not frequency of HFNS, predicted anxiety. However, once self-compassion was included in the model it was the only predictor of anxiety (β=-.46) and this relationship was significant for the items positive self-compassion (β=-0.37) and negatively worded self-coldness (β=.43). Interference of HFNS in everyday life may predict increased anxiety during menopause for some women. However, self-compassion may have a stronger relationship with anxiety than menopausal symptoms.


Sexual and reproductive health behaviors and experiences reported by young women with cystic fibrosis.
The prevalence of general and disease-specific sexual and reproductive health (SRH) concerns is unknown in the United States (U.S.) female CF population. This study aimed to describe and compare the SRH experiences and behaviors of young women with CF with the general U.S. Young women with CF ages 15-24years from five geographically diverse U.S. CF centers participated in a survey investigating SRH. Results were summarized and compared to the U.S. National Survey of Family Growth (NSFG) using logistic regression adjusting for confounders. A total of 188 young women with CF (mean age 19.7±2.7years) completed the survey; data were compared to 1997 NSFG respondents (mean age 19.6±0.10years). Fifty-four percent of women with CF reported having had vaginal sex with a male partner compared to 66% of U.S. women (p=0.55). Women with CF were less likely to have ever used contraception (55% vs. 74%, p=0.0001) or have been tested for sexually transmitted infections in the past year (19% vs. 34%, p=0.001) compared to the general population. Two percent of women with CF reported having ever been pregnant compared to 24% of U.S. women (p<0.0001). One-third of young women with CF reported perceived pubertal delay, 16% urinary incontinence, 16% sexual dysfunction, and 49% yeast infections. Young women with CF face significant SRH concerns and appear to be experiencing gaps in SRH care provision. Opportunities exist for intervention development around this aspect of comprehensive CF care. CF Foundation (KAZMER15A0); U.S. National Institutes of Health (UL1TR000005).


Synthesis of some new 2-(6-methoxy-2-naphthyl)- 5-aryl-1,3,4-oxadiazoles as possible non-steroidal anti-inflammatory and analgesic agents.
The synthesis of some new 2-(6-methoxy-2-naphthyl)-5-aryl-1,3,4-oxadiazoles (4a-k) has been described. Ethyl-6-methoxy-2-naphthoate (1) yielded on treatment with hydrazine hydrate to 6-methoxy-2-naphthoic acid hydrazide (2). Compound 2 reacted with substituted aromatic carboxylic acids (3a-k) in phosphorus oxychloride yielded 2-(6-methoxy-2-naphthyl)-5-aryl-1,3,4-oxadiazoles (4a-k). Newly synthesized compounds were characterized by IR, (1)H-NMR and mass spectral data. All the compounds were screened for their anti-inflammatory and analgesic activity. Compound 4j exhibited promising anti-inflammatory and analgesic activities.


Plasma concentrations of unconjugated and conjugated estrogens and gonadotrophins following application of various estrogen preparations after oophorectomy and in the menopause.
In 55 patients after oophorectomy and 20 women after natural menopause an oral estrogen replacement therapy was performed with estrone-sulfate, estradiol 17-valerate, estriol-succinate, a combination of micronized estradiol and estriol (Estrifam, Trisequens), and natural conjugated estrogens. In 4 patients a 3 mg estradiol per 5 g ointment substance was applied on the abdominal skin. The interindividual variations of estrogen increments during therapy were considerably high. Oral intake of 2 mg estriol-succinate daily was followed by a 500% increase of total (conjugated + unconjugated) estriol. Concentrations of unconjugated estrogens were not altered by this dosage. Following oral application of the other above mentioned preparations, prominent rises--especially of unconjugated estrogens in plasma--were noted. The concentration peaks occurred within 3--6 h after application. Unconjugated estradiol-17 beta in plasma was comparable with values of the follicular phase of a normal menstrual cycle, unconjugated estrone, however, was nonphysiologically high. Consequently, the E1/E2 ratio was greater than one whereas it is normally below one. 12 h after oral estrogen application, plasma estrogens dropped to almost initial values, so that a second medication seems to be necessary in order to guarantee an adequate supplementation over the course of the day. The hormone values determined in this study did not show significant differences between patients after a natural menopause and after oophorectomy. There was a positive correlation between rising estrogen levels and suppressed gonadotrophins during replacement therapy. The occurrence of climacteric symptoms did not exclusively depend on low estrogen and high gonadotrophin levels. Good tolerance of estrogen therapy with significantly elevated estrogen concentrations in plasma can be obtained transcutaneously in the form of estrogen ointments. Such therapy might simulate the physiological estrogen pattern even better than oral application does because of delayed and diluted steroid flow to the liver.


Orientation of capture antibodies on gold nanoparticles to improve the sensitivity of ELISA-based medical devices.
The sensitivity of ELISA-based devices strongly depends on the right orientation of antibodies on the sensor surface. The aim of this work was to increase the analytical performance of a commercial ELISA-based medical device (VIDAS®), thanks to the specific orientation of antibodies on gold nanostructured disposables. For this purpose, fPSA VIDAS® assay was used as model and the disposable providing the antigen binding surface (SPR®) was functionalized with gold nanostructures coated with monovalent half-fragment antibodies (reduced IgG, rIgG). The functionalization of polystyrene SPRs® with gold nanostructures was achieved through a one-step incubation of gold dispersions in a mixture of non-toxic solvents. Five different concentrations of gold nanoparticles (NPs) were tested with a maximum fluorescence enhancement for NPs density around 3-8 *103 NPs/μm2 (752 ± 11 RFV vs 316 ± 5 RFV of bare SPRs®). The comparison of the dose-response curve obtained with commercial and gold coated-SPRs® revealed a significant improvement (p < 0.0001) of the analytical sensitivity of the VIDAS® system using nanostructured disposables. This improved version of SPRs® allows to distinguish small variations of fPSA concentrations opening the way to the application of this biomarker to other kinds of cancer as recently described in the literature.


Analysis of snoring sound by psychoacoustic parameters.
The analysis of snoring sounds has been in focus for the past two decades. Conventional approaches by fast Fourier transformation face various limitations and demonstrate the necessity for alternative methods of investigation. Psychoacoustic analyses which are common for environmental noise analyses propose a potential approach. The present study investigates the psychoacoustic qualities (loudness, sharpness, roughness) of three different real snoring sounds (primary snoring, PS; Upper airway resistance syndrome, UARS; obstructive sleep apnea syndrome, OSAS) and their alterations under increasing, artificially created sound pressure levels (SPL) from 60-85 dB. PS and UARS were detected to obtain a greater loudness as well as a higher increase under increasing SPL than OSAS. The sharpness was higher in PS and UARS, remaining stable under rising SPL compared to OSAS. The intensities of roughness were at higher levels for PS compared to URAS and OSAS, with an increase of all snoring sounds under rising SPL. By merging the psychoacoustic qualities, an individual acoustic fingerprint can be created to differentiate the three types of snoring. A potential application is proposed for the analysis of snoring sounds during polysomnography as well as for an adequate evaluation of the annoyance by snoring sounds.


Importance of Chronological Changes on High-Resolution Vessel Wall Imaging for Diagnosis of Isolated Anterior Cerebral Artery Dissection.
The accurate diagnosis of isolated anterior cerebral artery dissection (iACA-D) is made difficult by the spatial resolution on conventional magnetic resonance imaging (MRI) techniques including time-of-flight magnetic resonance angiography that is too limited to detect minute arterial wall abnormalities. Recent advances in high-resolution vessel wall imaging (HRVWI), which can detect intramural hematomas (IMH), have improved the noninvasive diagnostic accuracy of iACA-D. However, despite the risk of overlooking minute IMH and aneurysmal dilations especially at the early disease stage, the utility of T1-weighted and T2-weighted HRVWI at each disease stage (i.e., acute, early subacute, late subacute and chronic) has not been evaluated thoroughly enough. This prompted us to undertake the present study to determine the diagnostic value of chronological changes of IMHs on T1-weighted HRVWI and arterial dilations on T2-weighted HRVWI to achieve the earliest possible and most accurate diagnosis of iACA-D. In addition to six patients with iACA-D, five previously reported iACA-D patients from three institutions for whom reliable information on HRVWI and its examination date was available were enrolled in this study. IMHs on T1-weighted HRVWI and aneurysmal dilations on T2-weighted HRVWI and their chronological changes were visually evaluated. Either or both of IMHs on T1-weighted HRVWI and aneurysmal dilations on T2-weighted HRVWI were detected in all our six patients and the five previously reported ones. The disease stage showed a notable influence on the degree of their visualization. In contrast to IMHs which are regarded as the gold standard for the diagnosis of intracranial dissections, aneurysmal dilations were identified in 80% of cases even at the acute stage, reaching 100% at the early subacute stage. Despite the excellent detection rate of IMHs at the late subacute stage (100%), their detectability is poor at the acute and early subacute stages (0 and 40%, respectively). The results of this study highlighted the importance of aneurysmal dilations on T2-weighted HRVWI as a diagnostic marker to raise suspicion of iACA-D at the acute and early subacute stages, and similarly IMHs on T1-weighted HRVWI to confirm the diagnosis of iACA-D at the late subacute stage. These stage-dependent detectability changes in IMHs and aneurysmal dilations make an understanding of the chronological changes of these abnormal imaging findings mandatory to achieve an early and accurate diagnosis of iACA-D.


Quantification of economic losses consecutive to infection of a dairy herd with bovine viral diarrhoea virus.
Production losses and treatment expenditures consecutive to bovine viral diarrhoea virus (BVDV) infection in a dairy herd were calculated by partial budgeting based on published estimates of production effects. Overall costs (losses plus expenditures) resulted in a decreased gross margin of 10.7 euros and 19.0 per 1000 l of milk for an average and severe infection, respectively. With a milk quota system allowing no lease of quota, assuming adjustment of the herd size by the farmer to produce the quota, decrease in gross margin was limited to 7.9 euros and 13.9 per 1000 l of milk.


Quantitative Proteomic Analysis of Mass Limited Tissue Samples for Spatially Resolved Tissue Profiling.
Traditionally, proteomic studies have been carried out on whole tissues or organs enabling the profiling of thousands of proteins within a single LC-MS analysis. A disadvantage of this approach is that proteomes generated from whole tissues are an "average" that represents a blend of cell types and distinct anatomical regions which can obscure important biological phenomena. Laser capture microdissection (LCM) is an elegant method that allows tissue features of interest, as small as a single cell, to be identified and isolated for downstream analysis. Herein we describe an approach that utilizes an immobilized enzyme reactor (IMER) coupled directly to nanoLC-MS/MS for highly sensitive, automated, quantitative proteomic analysis of the microscopic tissue specimens generated by LCM.


Capillary electrophoresis applied to DNA: determining and harnessing sequence and structure to advance bioanalyses (2009-2014).
This review of capillary electrophoresis methods for DNA analyses covers critical advances from 2009 to 2014, referencing 184 citations. Separation mechanisms based on free-zone capillary electrophoresis, Ogston sieving, and reptation are described. Two prevalent gel matrices for gel-facilitated sieving, which are linear polyacrylamide and polydimethylacrylamide, are compared in terms of performance, cost, viscosity, and passivation of electroosmotic flow. The role of capillary electrophoresis in the discovery, design, and characterization of DNA aptamers for molecular recognition is discussed. Expanding and emerging techniques in the field are also highlighted.


Interleukin 10 promotes macrophage uptake of HDL and LDL by stimulating fluid-phase endocytosis.
Highly elevated plasma levels of interleukin-10 (IL-10) are causally associated with "Disappearing HDL Syndrome" and low plasma LDL-cholesterol, but the underlying mechanism is poorly understood. Fluid-phase endocytosis, a process highly dependent on actin dynamics, enables cells to internalize relatively high amounts of extracellular fluids and solutes. We sought to investigate whether IL-10 induces lipoprotein uptake by fluid-phase endocytosis in macrophages. Macrophages (RAW264.7, Kupffer and human) were incubated with vehicle (PBS) or IL-10 (20 ng/ml) for 7 days. Uptake of HDL, LDL, and/or fluid-phase endocytosis probes (albumin-Alexa680®, 70 kDa FITC-Dextran and Lucifer Yellow, LY) was evaluated by FACS. Intracellular cofilin and phosphorylated cofilin (p-cofilin) levels were determined by immunoblotting. Macrophage uptake of lipoproteins and probes was non-saturable and increased after IL-10 incubation (p < 0.0001). Furthermore, pre-incubation with fluid-phase endocytosis inhibitors (LY294002, Latrunculin A, and Amiloride) significantly reduced uptake (p < 0.05). IL-10 increased the cofilin/p-cofilin ratio (p = 0.021), signifying increased cofilin activation and hence filamentous actin. Consistently, phalloidin staining revealed increased filamentous actin in macrophages after IL-10 treatment (p = 0.0018). Finally, RNA-seq analysis demonstrated enrichment of gene sets related to actin filament dynamics, membrane ruffle formation and endocytosis in IL-10-treated macrophages (p < 0.05). IL-10 did not alter mRNA levels of Ldlr, Vldlr, Scarb1, Cd36 or Lrp1. In primary human monocyte-derived macrophages and murine Kupffer cells, IL-10 incubation also increased uptake of lipoproteins, albumin and LY (p < 0.01). Interleukin-10 induces the uptake of HDL and LDL by fluid-phase endocytosis by increasing actin-filament rearrangement in macrophages, thus providing a plausible mechanism contributing to "Disappearing HDL Syndrome".


Observations on changes in ventricular repolarization following four weeks of exercise training in chronic heart failure patients.
The aim of this study was to investigate the effects of exercise training on ventricular repolarization dynamicity and heart rate variability in chronic heart failure patients. A total of 22 chronic heart failure patients with reduced ejection fraction in sinus rhythm were included in the study. The patients were in NYHA classes II-III with an ejection fraction of 29.7 ± 7.7%. Before and after 4 weeks of aerobic exercise training, all patients performed a cardiopulmonary exercise test, a standard twelve-lead electrocardiogram and a 24 h Holter recording from which heart rate variability and ventricular repolarization dynamicity were assessed. We observed a significant decrease of QTpeak (p < .001) and QTend (p < .001) at RR intervals ranging from 600 to 1000 ms on 24 h QT/RR regressions after 4 weeks of exercise training. Our analyses revealed that short-term exercise training induced significant changes in the frequency and time domain HRV parameters on an overall time-period of 24 h. Four weeks of exercise training induced significant changes in ventricular repolarization dynamicity in chronic heart failure patients. In addition, short-term exercise training was enough to improve patients' heart rate variability.


Gastrointestinal tract Candida spp colonization shows mostly a monoclonal pattern: an intra-patient pilot study.
Gastrointestinal tract Candida genotypes may associate with isolates later causing infections. We genotyped Candida spp isolates (n = 200 individual colonies) from rectal swabs to assess whether gastrointestinal gut colonization is caused by a single genotype (monoclonal pattern) or a combination of them (polyclonal pattern). C. glabrata showed a sheer monoclonal pattern. C. parapsilosis and C. tropicalis showed a monoclonal pattern involving the presence of either exclusively identical genotypes or a combination of clonally-related genotypes; in the latter case, a dominant genotype was always found. C. albicans showed mostly a polyclonal pattern involving a combination of dominant clonally-related genotypes and unrelated genotypes. We genotyped C. albicans, C. parapsilosis, C. tropicalis, and C. glabrata isolates prospectively from rectal swabs to study the gastrointestinal colonization pattern in the patients. Gastrointestinal tract colonization is mostly monoclonal and commonly dominated by one genotype.


The anti-inflammatory activity of duloxetine, a serotonin/norepinephrine reuptake inhibitor, prevents kainic acid-induced hippocampal neuronal death in mice.
Duloxetine (DXT), a potent serotonin/norepinephrine reuptake inhibitor, is widely used in the treatment of major depressive disorder. In the present study, we examined the effects of DXT treatment on seizure behavior and excitotoxic neuronal damage in the mouse hippocampal CA3 region following intraperitoneal kainic acid (KA) injection. DXT treatment showed no effect on KA-induced behavioral seizure activity. However, treatment with 10mg/kg DXT reduced KA-induced neuronal death in the hippocampal CA3 region at 72h after KA administration, and treatment with 20 and 40mg/kg DXT showed a noticeable neuroprotection in the hippocampal CA3 region after KA injection. In addition, KA-induced activations of microglia and astrocytes as well as KA-induced increases of TNF-α and IL-1β levels were also suppressed by DXT treatment. These results indicate that DXT displays the neuroprotective effect against KA-induced excitotoxic neuronal death through anti-inflammatory action.


Teleconsultation in a coloproctology unit during the COVID-19 pandemic. Preliminary results.
During the state of alarm established in Spain due to the COVID-19 pandemic, most of the face-to-face outpatient consultations were cancelled and a telephone consultation was established to follow up coloproctological patients. The objective of this study was to analyse the efficacy of telemedicine (by telephone) in monitoring patients in a coloproctology unit, in the context of the COVID-19 pandemic. Prospective descriptive study of consecutive patients in a single centre. The result of the teleconsultation was classified as discharge, resolved visit or reprogramming and was analysed by different diagnostic groups. From March 19th to April 17th, 2020, the teleconsultation of 190 patients was carried out. The response rate was 94.2% (179). The diagnostic categories of the patients attended were: 51 (26.9%) colorectal neoplasia, 48 (25.3%) proctological pathology, 72 (37.9%) pelvic floor dysfunctions and 19 (10%) other benign pathologies. 105 (55.26%) could be recited as if they had come in person. Eleven (5.8%) patients were discharged. No significant differences were found between the different diagnostic categories and the resolution of the teleconsultation. The reasons for reprogramming are analyzed in the study. In the context of a pandemic, teleconsultation has allowed 61% of follow-up visits to be definitively solved, avoiding the reprogramming of 116 patients. The new social and health paradigm after the pandemic will require a rethinking of our healthcare model, and in many aspects, telemedicine can offer tools for this.


Who is omitted from repeated offline HIV behavioural surveillance among MSM? Implications for interpreting trends.
Repeated behavioural surveillance should sample all epidemiologically relevant subgroups to provide a complete picture of trends in HIV risk behaviours. Web-based recruitment has been mooted but little empirical data exist on country experiences. We describe who is omitted from three rounds of a conventional offline-only surveillance programme among men who have sex with men (MSM) 2006-2011, but recruited subsequently on Internet dating sites, and the implications of this for understanding trends. The latter were younger, less gay identified and less gay community attached. Importantly, they reported different partnering patterns, lower condom use with casual and fuckbuddy-type male partners, and lower rates of HIV testing, compared to MSM routinely captured in offline surveillance. The replacement of offline socio-sexual activity by the Internet among many MSM means that current venue-based surveillance systems may underestimate risk behaviours, overlook trends among unsampled online MSM, and misinterpret trends observed in sampled MSM due to "sample drift" of most-at-risk MSM.


Reproducibility of DXA estimations of body fat in HIV lipodystrophy: implications for clinical research.
Dual-energy X-ray absorptiometry (DXA) estimates of body fat are increasingly used for the evaluation of human immunodeficiency virus lipodystrophy (HIV LD); however, limited data are available on their reproducibility. This information is essential for using this tool as an end point in treatment trials or as a diagnostic tool. This study evaluates the reproducibility of DXA body fat estimation in HIV-positive subjects with and without lipodystrophy. Thirty subjects representing a spectrum of severity of fat redistribution underwent same-day repeat whole-body DXA scans (Hologic QDR 4500A scanner). Root mean square coefficients of variation (RMS-CV) were used to estimate minimum detectable differences (MDDs) for body fat content in different regions. Absolute MDD was calculated by multiplying the MDD by the mean fat-mass value for each anatomical area. The RMS-CV ranged from 4.0% for arm fat to 1.6% for total fat. Relative and absolute MDD values ranged from 11.0% or 160 g for arm fat to 4.3% or 628 g for total fat. DXA measurements of regional body fat mass in subjects with HIV show similar reproducibility to other populations. Minimal detectable differences were smaller than differences observed in published studies for all measurements. DXA is a sensitive tool for detecting changes in peripheral fat among patients with HIV lipodystrophy.


Reproducibility of Circumpapillary Retinal Nerve Fiber Layer Thickness Measurements Evaluated by Circle and Annulus Area With and Without Correction for Ocular Rotation.
To compare the reproducibility of annulus area measurements of the circumpapillary retinal nerve fiber layer thickness (cpRNFLTannulus) using spectral-domain optical coherence tomography (SD-OCT) with that of conventional cpRNFLT (cpRNFLTring) measurements and evaluate the effect of correction of ocular rotation on the reproducibility. Peripapillary SD-OCT raster scans were performed on 2 different days in 48 normal subjects and 59 patients with glaucoma using the Topcon OCT-1000. In the raster scan dataset, the cpRNFLTring and cpRNFLTannulus were averaged along a circle (3.4-mm diameter) and in an annulus area (diameters from 2.8 to 4.0 mm) centered on the barycenter of the disc. The measurement reproducibility, effects of ocular rotational correction, and factors affecting the reproducibility were studied. The intervisit reproducibility values, expressed as the coefficients of variation, for the cpRNFLTannulus, were significantly smaller than those for the cpRNFLTring measurements in sectors 30 degrees wide in glaucomatous eyes (P=0.006) and in sectors 10 degrees wide in normal and glaucomatous eyes (P<0.001). The ocular rotational angles averaged 7.1 and 7.2 degrees with intervisit differences of 1.4 and 1.8 degrees, respectively, in normal and glaucomatous eyes. Correction for the ocular rotation had little effect on the reproducibility. The mean deviation and cpRNFLT were correlated negatively with the coefficient of variation (β=-0.93 to -0.83; P=0.027 to 0.028). The cpRNFLTannulus measurement yielded better reproducibility than the cpRNFLTring measurement, and multiple linear regression analysis showed that the more advanced the glaucomatous damage, the worse the intervisit reproducibility.


Multiple perspectives reveal the gut toxicity of polystyrene microplastics on Eisenia fetida: Insights into community signatures of gut bacteria and their translocation.
The gut is the primary pathway by which soil animals are exposed to microplastics (MPs). However, the gut toxicity of MPs has not been elucidated in earthworms. Herein, we aimed to study the gut toxicity (e.g., gut barrier dysfunction, gut bacterial translocation, and pathogen invasion) of polystyrene microplastics (PS-MPs) on Eisenia fetida and its relationship with gut bacteria. We found that PS-MPs exposure caused gut barrier damage to Eisenia fetida. This damage included apparent injury of gut epithelial cells and significantly lower transcription levels of genes coding for gut tight junction (TJ)-related proteins. We then observed significantly increased levels of bacterial lipopolysaccharide (LPS) and gut bacterial load, indicating the occurrence of gut bacterial translocation and related barrier damage. Subsequently, antibacterial immune responses were activated and accompanied by a failure of the antioxidant defense system, indicating that pathogen invasion might occur. Gut barrier damage could weaken host selective pressures (deterministic process) on gut bacteria, such as particular pathogens. Indeed, members of Proteobacteria, e.g., Aeromonas and Escherichia/Shigella, regarded as potential opportunistic pathogens, were remarkable signatures of groups exposed to PS-MPs. These potential opportunistic gut bacteria were pivotal contributors to gut TJ damage and gut bacterial translocation resulting from PS-MPs exposure. In addition, the gut bacterial networks of PS-MPs exposure groups were more uncomplicated than those of the control group, but more negative interactions were easy to observe. In conclusion, our work sheds light on the molecular mechanism of earthworm gut toxicity caused by PS-MPs exposure and provides a prospective risk assessment of MPs in soil ecosystems.


Scaphoid Reconstruction.
Surgical strategies for scaphoid nonunions become more complex based on time from injury to treatment. The decision-making process, however, can follow a logical sequence. Scaphoid nonunions less than 1 year after trauma and no carpal malalignment can be treated with percutaneous screw fixation under fluoroscopic and/or arthroscopic guidance. Reinterventions or patients with avascular proximal poles that do not need substantial grafts are reliably treated with pedicle vascularized bone grafts. Resection of the distal pole of the scaphoid is a good option in old nonunions or after a failed scaphoid procedures. When there are radioscaphoid degenerative changes, salvage procedures such as proximal row carpectomy (PRC) should be considered.


Stimulating forebrain communications: Slow sinusoidal electric fields over frontal cortices dynamically modulate hippocampal activity and cortico-hippocampal interplay during slow-wave states.
Slow-wave states are characterized by the most global physiological phenomenon in the mammalian brain, the large-amplitude slow oscillation (SO; ~1Hz) composed of alternating states of activity (ON/UP states) and silence (OFF/DOWN states) at the network and single cell levels. The SO is cortically generated and appears as a traveling wave that can propagate across the cortical surface and can invade the hippocampus. This cortical rhythm is thought to be imperative for sleep-dependent memory consolidation, potentially through increased interactions with the hippocampus. The SO is correlated with learning and its presumed enhancement via slow rhythmic electrical field stimulation improves subsequent mnemonic performance. However, the mechanism by which such field stimulation influences the dynamics of ongoing cortico-hippocampal communication is unknown. Here we show - using multi-site recordings in urethane-anesthetized rats - that sinusoidal electrical field stimulation applied to the frontal region of the cerebral cortex creates a platform for improved cortico-hippocampal communication. Moderate-intensity field stimulation entrained hippocampal slow activity (likely by way of the temporoammonic pathway) and also increased sharp-wave ripples, the signature memory replay events of the hippocampus, and further increased cortical spindles. Following cessation of high-intensity stimulation, SO interactions in the cortical-to-hippocampal direction were reduced, while the reversed hippocampal-to-cortical communication at both SO and gamma bandwidths was enhanced. Taken together, these findings suggest that cortical field stimulation may function to boost memory consolidation by strengthening cortico-hippocampal and hippocampo-cortical interplay at multiple nested frequencies in an intensity-dependent fashion.


The unusual case: persistence of metaphyseal changes in penicillin treated congenital syphilis.
A case of congenital syphilis is described in which the diagnosis was not made until the age of 9 and with persistance of metaphyseal changes in spite of prolonged penicillin treatment.


Oxidative stress injury in doxorubicin-induced cardiotoxicity.
Doxorubicin (DOX) is widely used as a broad-spectrum anti-tumor anthracycline to treat various cancers. The serious adverse effects of DOX on cardiotoxicity limit its clinical application. There are several different mechanisms involved in DOX-induced cardiotoxicity. Oxidative stress (OS) is caused by an imbalance between reactive oxygen species (ROS) and endogenous antioxidants in response to injury, which can lead to myocardial toxicity. The aim of this review was to investigate the mechanisms underlying the effects of oxidative stress injury on myocardial toxicity, from three different aspects: the increase in downstream oxidative stress products, the reduction in upstream antioxidative stress products, and subcellular organelles. Finally, there are some anti-oxidative drugs that show efficacy in limiting DOX-induced cardiotoxicity. It is necessary to fully understand the toxicity of DOX to the myocardium and achieve symptomatic treatment.


Pyroglyphid mites as a source of work-related allergens.
Pyroglyphid mites are primarily associated with allergen exposure at home; hence the name house dust mites. However, we have found numerous studies reporting pyroglyhid mite levels in public and occupational settings. This review presents the findings of house dust mite allergens (family Pyroglyphidae, species Dermatophagoides) as potential work-related risk factors and proposes occupations at risk of house dust mite-related diseases. Pyroglyphid mites or their allergens are found in various workplaces, but clinically relevant exposures have been observed in hotels, cinemas, schools, day-care centres, libraries, public transportation (buses, trains, taxies, and airplanes), fishing-boats, submarines, poultry farms, and churches. Here we propose a classification of occupational risk as low (occasional exposure to mite allergen levels up to 2 μg g(-1)), moderate (exposure between 2 μg g(-1) and 10 μg g(-1)), and high (exposure >10 μg g(-1)). The classification of risk should include factors relevant for indoor mite population (climate, building characteristics, and cleaning schedule). To avoid development or aggravation of allergies associated with exposure to house dust mites at work, occupational physicians should assess exposure risk at work, propose proper protection, provide vocational guidance to persons at risk and conduct pre-employment and periodic examinations to diagnose new allergy cases. Protection at work should aim to control dust mite levels at work. Measures may include proper interior design and regular cleaning and building maintenance.


Elevated cardiac hemoglobin expression is associated with a pro-oxidative and inflammatory environment in primary mitral regurgitation.
Primary mitral regurgitation (PMR) is associated with oxidative and inflammatory myocardial damage. We reported greater exosome hemoglobin (Hb) in pericardial fluid (PCF) versus plasma, suggesting a cardiac source of Hb. Test the hypothesis that Hb is produced in the PMR heart and is associated with increased inflammation. Hb gene expression for subunits alpha (HBA) and beta (HBB) was assessed in right atria (RA), left atria (LA) and left ventricular (LV) tissue from donor hearts (n = 10) and PMR patient biopsies at surgery (n = 11). PMR patients (n = 22) had PCF and blood collected for macrophage markers, pro-inflammatory cytokines, and matrix metalloproteinases (MMPs). In-situ hybridization for HBA mRNA and immunohistochemistry for Hb-alpha (Hbα) and Hb-beta (Hbβ) protein was performed on PMR tissue. HBA and HBB genes are significantly increased (>4-fold) in RA, LA, and LV in PMR vs. normal hearts. In PMR tissue, HBA mRNA is expressed in both LV cardiomyocytes and interstitial cells by in-situ hybridization; however, Hbα and Hbβ protein is only expressed in interstitial cells by immunohistochemistry. PCF oxyHb is significantly increased over plasma along with low ratios (<1.0) of haptoglobin:oxyHb and hemopexin:heme supporting a highly oxidative environment. Macrophage chemotactic protein-1, tumor necrosis factor-α, interleukin-6, and MMPs are significantly higher in PCF vs. plasma. There is increased Hb production in the PMR heart coupled with the inflammatory state of the heart, suggests a myocardial vulnerability of further Hb delivery and/or production during cardiac surgery that could adversely affect LV functional recovery.


Cross-sectional study on prevalence and molecular characteristics of plasmid mediated ESBL/AmpC-producing Escherichia coli isolated from veal calves at slaughter.
The presence of ESBL/AmpC-producing E. coli in cattle has been reported previously, however information on veal calves is limited. This study describes the prevalence and molecular characteristics of E. coli with non-wild type susceptibility to cefotaxime in veal calves at slaughter. Faecal samples from 100 herds, 10 individual animals per herd, were screened for E. coli with non-wild type susceptibility for cefotaxime. Molecular characterization of ESBL/AmpC genes and plasmids was performed on one isolate per herd by microarray, PCR and sequence analysis. 66% of the herds were positive for E. coli with non-wild type susceptibility for cefotaxime. Within-herd prevalence varied from zero to 90%. 83% of E. coli producing ESBL/AmpC carried bla(CTX-M) genes, of which bla(CTX-M-1), bla(CTX-M-14) and bla(CTX-M-15) were most prevalent. The dominant plasmids were IncI1 and IncF-type plasmids. A relatively high prevalence of various bla(CTX-M) producing E. coli was found in veal calves at slaughter. The genes were mainly located on IncI1 and IncF plasmids.


Escherichia coli in different animal feces: phylotypes and virulence genes.
In this study, it was aimed to determine the phylogroups of Escherichia coli isolates from horse, cat, dog, sheep, cattle, and chicken feces samples and to investigate some important virulence genes of the isolates. For this purpose, a total of 600 feces samples, 100 from each animal species, were used as material. For the isolation of E.coli, feces samples were directly inoculated on MacConkey agar. The identification of the isolates was performed via phenotypic tests and species-specific multiplex Polymerase Chain Reaction (mPCR) method. PCR methods were used to phylotype E.coli isolates and to investigate virulence genes (bfpA, eaeA, LT, ST, Stx1, and Stx2). Of the total 600 E.coli isolates recovered in this study, 120 (20%), 269 (44.8%), 58 (9.7%), 19 (3.2%), 35 (5.8%), 56 (9.3%), 31 (5.2%), and 12 (2%) were identified as phylogroup A, B1, B2, C, D, E, F, and Escherichia clade I, respectively. While the virulence gene was detected in 149 (24.8%) E.coli isolates, no virulence gene was detected in 451 (75.2%) isolates. According to the analysis results, the most determined virulence gene was Stx1, while the least determined virulence gene was LT. In conclusion, in this study, when both the animal species and the number of E.coli isolates examined are considered, the data obtained are of great importance in epidemiological terms. However, the detection of virulence genes in 13.5% among phylogroup A, B1, and C isolates with commensal characteristics suggest that these isolates may show pathogenic characteristics with the virulence genes they contain.


A comprehensive model of the crypts of the small intestine of the mouse provides insight into the mechanisms of cell migration and the proliferation hierarchy.
A comprehensive model has been formulated for the proliferative behaviour of the crypts of the small intestine based on individual cell to cell relationships rather than on the average effects of all cells. The model accommodates a wide range of cell kinetic data and provides an insight into the mechanisms involved in cell movement within the columnar sheet of cells and into the relationship between the stem cells and their progeny. The model permits the number of stem cells and transit generations to be estimated. The number of stem cells is predicted to be not less than 4 and not more than 16 per crypt with cell cycle times of between 12 and 32 h respectively. Certain conclusions can be drawn concerning the mechanisms involved in the initial cell displacements after cell division. The model also allows an estimation of parameters which cannot be measured directly such as the degree of cell generation disorder and the amount of dispersion of cells within a cell lineage.


Ultrafast thin-disk multipass laser amplifier delivering 1.4 kW (4.7 mJ, 1030 nm) average power converted to 820 W at 515 nm and 234 W at 343 nm.
We report on an Yb:YAG thin-disk multipass laser amplifier delivering sub-8 ps pulses at a wavelength of 1030 nm with 1420 W of average output power and 4.7 mJ of pulse energy. The amplifier is seeded by a regenerative amplifier delivering 6.5 ps pulses with 300 kHz of repetition rate and an average power of 115 W. The optical efficiency of the multipass amplifier was measured to be 48% and the beam quality factor was better than M2 = 1.4. Furthermore we report on the external second harmonic generation from 1030 nm to 515 nm using an LBO crystal leading to an output power of 820 W with 2.7 mJ of energy per pulse. This corresponds to a conversion efficiency of 70%. Additionally, 234 W of average power were obtained at the third harmonic with a wavelength of 343 nm.


[Assessment of the correlation between histological degeneration and radiological and clinical parameters in a series of patients who underwent lumbar disc herniation surgery].
The use of histological degeneration scores in surgically-treated herniated lumbar discs is not common in clinical practice and its use has been primarily restricted to research. The objective of this study is to evaluate if there is an association between a higher grade of histological degeneration when compared with clinical or radiological parameters. Retrospective consecutive analysis of 122 patients who underwent single-segment lumbar disc herniation surgery. Clinical information was available on all patients, while the histological study and preoperative magnetic resonance imaging were also retrieved for 75 patients. Clinical variables included age, duration of symptoms, neurological deficits, or affected deep tendon reflex. The preoperative magnetic resonance imaging was evaluated using Modic and Pfirrmann scores for the affected segment by 2 independent observers. Histological degeneration was evaluated using Weiler's score; the presence of inflammatory infiltrates and neovascularization, not included in the score, were also studied. Correlation and chi-square tests were used to assess the association between histological variables and clinical or radiological variables. Interobserver agreement was also evaluated for the MRI variables using weighted kappa. No statistically significant correlation was found between histological variables (histological degeneration score, inflammatory infiltrates or neovascularization) and clinical or radiological variables. Interobserver agreement for radiological scores resulted in a kappa of 0.79 for the Pfirrmann scale and 0.65 for the Modic scale, both statistically significant. In our series of patients, we could not demonstrate any correlation between the degree of histological degeneration or the presence of inflammatory infiltrates when compared with radiological degeneration scales or clinical variables such as the patient's age or duration of symptoms.


Does an active play standard change childcare physical activity and healthy eating policies? A natural policy experiment.
In 2017, the provincial government of British Columbia (BC) implemented a mandatory policy outlining Active Play Standards (AP Standards) to increase physical activity (PA) levels, sedentary and motor skills among children attending licensed childcare centers. Concurrently, a capacity-building initiative was launched to help implement policies and practices supporting both PA and healthy eating (HE) in the early years. This study evaluated differences in center-level PA and HE policies and practices before and after the enforcement of the new provincial AP Standards. Using a repeat cross-sectional design, surveys were distributed to managers and staff of licensed childcare facilities serving children aged 2-5 years before (2016-2017 or 'time 1') and after (2018-2019 or 'time 2') implementation of the AP Standards across BC. The total sample included 1,459 respondents (910 and 549 respondents at time 1 and time 2, respectively). Hierarchical mixed effects models were used to examine differences in 9 and 7 PA/sedentary policies and practices, respectively, as well as 11 HE policies between time 1 and time 2. Models controlled for childcare size and area-level population size, education, and income. Compared to centers surveyed at time 1, centers at time 2 were more likely to report written policies related to: fundamental movement skills, total amount of Active Play (AP) time, staff-led AP, unfacilitated play/free play, total amount of outdoor AP time, limiting screen time, breaking up prolonged sitting, staff role modeling of PA, and training staff about PA (P < 0.01 for all 9 policies examined). Compared to time 1, centers at time 2 reported more frequent practices related to ensuring children engaged in at least 120 min of AP, 60 min of outdoor AP daily, and limiting screen time (P < 0.01 for 3 out of 7 practices examined). Despite no additional policy intervention related to HE, centers were more likely to report having written policies related to: HE education for children, encouraging new foods, having family-style meals, offering only milk or water, limiting the amount of juice served, staff role modeling of HE, limiting the types of foods at parties/celebrations and foods brought from home (P < 0.05 for 9 out of 11 HE policies). Approximately a year after the implementation of a governmental policy targeting PA supported by a capacity-building initiative, childcare centers reported positive changes in all 9 PA/sedentary policies examined, all 3 out of 7 PA/sedentary practices and 9 out of 11 HE policies evaluated at the center-level.


Local immunosuppressive therapy with monoclonal anti-T cell antibody on renal allograft survival in the rat.
Considerable interest in the experimental and clinical use of MoAbs as potential therapeutic agents in allograft rejection has been generated by the recent reports of striking prolongation. In this study we investigated the efficacy of the local administration of MoAb OX-19 which is directed to the rat CD5 equivalent, through the renal artery using a rat kidney transplant model, in order to develop a potent method for modifying rejection while minimizing the systemic side effects. Untreated Lewis rats (LEW, RT-1(1)) rejected Brown-Norway rat (BN, RT-1n) kidney at 7.8 +/- 0.2 days (n = 10). Mean survival time (MST) of recipients treated with OX-19 (75 micrograms/kg per day) as single bolus injections via the dorsal penile vein for 7 days was 7.0 +/- 0.2 days (n = 5, NS). LEW hosts receiving OX-19 (75 micrograms/kg per day) continuously for 7 days via a femoral vein by using an osmotic minipump (IV-treated group) showed a slight prolongation of graft survival (MST = 8.8 +/- 0.9 days, n = 5), but this was not statistically significant. On the other hand, local continuous intrarenal arterial infusion of OX-19 (75 micrograms/kg per day) for 7 days (RA-treated group) significantly prolonged the graft survivals (MST = 16.8 +/- 1.3 days, n = 8, P < 0.01). Histological examination of MoAb-treated LEW hosts on day 6 post-grafting revealed that kidney grafts from RA-treated hosts showed a slight tubular necrosis, but reduced mononuclear cell infiltration, whereas kidney grafts from IV-treated hosts displayed a severe mononuclear cell infiltration around the artery with interstitial oedema. Moreover, the local intrarenal administration of OX-19, even when the dose is delayed until day 4 after renal grafting, has a therapeutic effect for on-going acute allograft rejection (MST = 11.4 +/- 0.8 days, n = 8) compared with administration of OX-19 intravenously from day 4 after grafting (MST = 7.6 +/- 0.2 days, n = 5, P < 0.01) or with no treatment (MST = 7.8 +/- 0.2 days, P < 0.01). The phenotype of graft infiltrating cells (GIC) was investigated on day 6 post-grafting. There was a significantly lower percentage of cells positive for OX-19, OX-8, OX-26 (transferrin receptor), and OX-39 (IL-2 receptor) in the RA group than in the IV group.(ABSTRACT TRUNCATED AT 400 WORDS)


[Takayasu's arteritis: vascular investigations and therapeutic management. Experience with 16 patients].
There is no consensus in regard to vascular explorations and therapeutical management of Takayasu's arteritis. The objective of this study was therefore to establish the most appropriate vascular explorations and to analyze current treatments. Clinical, biological and morphological findings related to either diagnosis or treatment were retrospectively evaluated in sixteen patients diagnosed with Takayasu's arteritis according to the American College of Rheumatology criteria. Median delay between the occurrence of the first symptoms and the diagnosis was 9 months. Aortic lesions and aortic valvular incompetence were more frequent. Statistical analysis showed the existence of a correlation between the lack of relapse and corticosteroid therapy (Fisher exact test, P = 0.021). Percutaneous transluminal angioplasty led to stabilization of vascular lesions. Surgical management led to satisfactory results, except for patients with aortic lesions, as survival was then less than 1 year. Early diagnosis is mandatory in patients with Takayasu's arteritis in order to propose appropriate therapy, particularly corticosteroid therapy. Surgery and angioplasty prove to be useful in occlusive forms. Late diagnosis is accompanied by severe aortic lesions and fatal outcome.


Ethanol production in a membrane bioreactor: pilot-scale trials in a corn wet mill.
Pilot plant trials were conducted in a corn wet mill with a 7000-L membrane recycle bioreactor (MRB) that integrated ceramic microfiltration membranes in a semi-closed loop configuration with a stirred-tank reactor. Residence times of 7.5-10 h with ethanol outputs of 10-11.5% (v/v) were obtained when the cell concentration was 60-100 g/L dry wt of yeast, equivalent to about 10(9)-10(10) cells/mL. The performance of the membrane was dependent on the startup mode and pressure management techniques. A steady flux of 70 L/(m2 x h) could be maintained for several days before cleaning was necessary. The benefits of the MRB include better productivity; a clear product stream containing no particulates or yeast cells, which should improve subsequent stripping and distillation operations; and substantially reduced stillage handling. The capital cost of the MRB is $21-$34/(m3 x yr) ($0.08-$0.13/[gal x yr]) of ethanol capacity. Operating cost, including depreciation, energy, membrane replacement, maintenance, labor, and cleaning, is $4.5-9/m3 ($0.017-$0.034/gal) of ethanol.


EIF4A3-Induced circARHGAP29 Promotes Aerobic Glycolysis in Docetaxel-Resistant Prostate Cancer through IGF2BP2/c-Myc/LDHA Signaling.
Docetaxel-based chemotherapy is a standard-of-care treatment for metastatic prostate cancer, and chemoresistance remains a major challenge in clinical practice. Recent studies have demonstrated that circular RNAs (circRNA) play critical roles in the development and progression of prostate cancer. However, the biological roles and potential functions of circRNAs in mediating docetaxel-resistant prostate cancer have yet to be well elucidated. In this study, we analyzed the expression profiles of circRNAs in docetaxel-resistant and -sensitive prostate cancer cells through RNA sequencing and found that expression of circARHGAP29 was significantly upregulated in docetaxel-resistant cell lines and clinical samples. Ectopic expression of circARHGAP29 triggered docetaxel resistance and aerobic glycolysis in prostate cancer cells, which was reduced by silencing circARHGAP29. Moreover, eukaryotic initiation factor 4A3, which bound the back-spliced junction site and the downstream flanking sequence of circARHGAP29, induced cyclization and cytoplasmic export of circARHGAP29. circARHGAP29 increased the stability of lactate dehydrogenase A (LDHA) mRNA by strengthening its interaction with insulin-like growth factor 2 mRNA-binding protein 2, leading to enhanced glycolytic metabolism. In addition, circARHGAP29 interacted with and stabilized c-Myc mRNA and protein, which further increased LDHA expression by facilitating its transcription. These findings reveal the crucial function of circARHGAP29 in prostate cancer glycolysis by increasing and stabilizing LDHA mRNA, providing a promising therapeutic target in docetaxel-resistant prostate cancer. Upregulation of a novel circRNA, circARHGAP29, promotes docetaxel resistance and glycolytic metabolism, suggesting it could be a prognostic biomarker and therapeutic target in chemoresistant prostate cancer.


Patient selection and the physiology of gastrointestinal antiobesity operations.
Antiobesity surgery largely is "behavioral surgery"--the results rely on behavioral factors more than on the technical performance of the procedure. Therefore, patient selection and pre- and postoperative patient education are critical for outcome. The operations rely on mechanical and biochemical mechanisms, such as: (1)limiting food consumption through restriction by activating satiety or nimiety; (2) increasing or decreasing appetitive gastrointestinal peptides; and (3) reducing substrate stores by way of malabsorption or increased thermogenesis to ensure weight loss. The balance between physiologic mechanisms that promote weight loss and motivational factors that cause maladaptive eating is the greatest challenge to effective surgical treatment of obesity.


High-resolution biophysical analysis of the dynamics of nucleosome formation.
We describe a biophysical approach that enables changes in the structure of DNA to be followed during nucleosome formation in in vitro reconstitution with either the canonical "Widom" sequence or a judiciously mutated sequence. The rapid non-perturbing photochemical analysis presented here provides 'snapshots' of the DNA configuration at any given moment in time during nucleosome formation under a very broad range of reaction conditions. Changes in DNA photochemical reactivity upon protein binding are interpreted as being mainly induced by alterations in individual base pair roll angles. The results strengthen the importance of the role of an initial (H3/H4)2 histone tetramer-DNA interaction and highlight the modulation of this early event by the DNA sequence. (H3/H4)2 binding precedes and dictates subsequent H2A/H2B-DNA interactions, which are less affected by the DNA sequence, leading to the final octameric nucleosome. Overall, our results provide a novel, exciting way to investigate those biophysical properties of DNA that constitute a crucial component in nucleosome formation and stabilization.


High-throughput screening of filamentous fungi using nanoliter-range droplet-based microfluidics.
Filamentous fungi are an extremely important source of industrial enzymes because of their capacity to secrete large quantities of proteins. Currently, functional screening of fungi is associated with low throughput and high costs, which severely limits the discovery of novel enzymatic activities and better production strains. Here, we describe a nanoliter-range droplet-based microfluidic system specially adapted for the high-throughput sceening (HTS) of large filamentous fungi libraries for secreted enzyme activities. The platform allowed (i) compartmentalization of single spores in ~10 nl droplets, (ii) germination and mycelium growth and (iii) high-throughput sorting of fungi based on enzymatic activity. A 10(4) clone UV-mutated library of Aspergillus niger was screened based on α-amylase activity in just 90 minutes. Active clones were enriched 196-fold after a single round of microfluidic HTS. The platform is a powerful tool for the development of new production strains with low cost, space and time footprint and should bring enormous benefit for improving the viability of biotechnological processes.


Expression of the butyrophilin gene, a milk fat globule membrane protein, is associated with the expression of the alpha S1casein gene.
Previous in situ hybridization studies from our laboratory have shown that expression of certain milk protein genes, e.g. alpha-lactalbumin, is very high in most parts of the mammary glands of sheep and cattle, while in other areas containing an abundance of fat globules it is virtually zero (Molenaar et al., 1992). One possible explanation is that some areas of the mammary gland are dedicated to protein synthesis and some to fat synthesis. To check this possibility, the cRNA for butyrophilin, a milk-fat globule membrane protein, and hence a putative marker of milk fat synthesis, was used as a probe in in situ hybridization studies. The results show quite clearly that the patterns of expression for this gene are similar, cell type for cell type, as those for milk protein genes such as alpha-lactalbumin and alpha S1casein. In addition, we found that butyrophilin gene expression more closely matches that of alpha S1casein than that of alpha-lactalbumin. If it is shown in the future that butyrophilin is indeed a marker for milk fat synthesis, then these results support the current assumption that fat and protein synthesis do occur in the same cell.


Awareness and Use of South Asian Tobacco Products Among South Asians in New Jersey.
South Asians are the third largest Asian group in the US and among the fastest growing racial groups in New Jersey. Tobacco consumption among South Asians is characterized by several smoked and smokeless tobacco products indigenous to the Indian subcontinent. However, there is a paucity of research on tobacco use behaviors among South Asians in the US. The goal of this study was to examine the awareness and use of South Asian tobacco products such as bidis, gutkha, paan, paan masala, and zarda as well as other potentially carcinogenic products such as supari, their context of use, and their cultural significance among South Asians living in the US. Eight focus groups were conducted with South Asian adults living in Central New Jersey. Overall, participants were aware of a wide variety of foreign and American tobacco products with older South Asians identifying a greater variety of indigenous products compared to younger South Asians. Hookah was consistently recognized as popular among the younger generation while products such as paan or paan masala were more commonly identified with elders. Use of tobacco-related products such as paan and supari were described as common at social gatherings or after meals. In addition, light or social users of South Asian tobacco products, including products not consistently defined as tobacco, may not report tobacco use on a survey. Better understanding of the use of these products among South Asians and how some may classify tobacco usage can inform future research and public health interventions in these communities.


The Role of Spinal GABAB Receptors in Cancer-Induced Bone Pain in Rats.
Cancer-induced bone pain (CIBP) remains a major challenge in advanced cancer patients because of our lack of understanding of its mechanisms. Previous studies have shown the vital role of γ-aminobutyric acid B receptors (GABABRs) in regulating nociception and various neuropathic pain models have shown diminished activity of GABABRs. However, the role of spinal GABABRs in CIBP remains largely unknown. In this study, we investigated the specific cellular mechanisms of GABABRs in the development and maintenance of CIBP in rats. Our behavioral results show that acute as well as chronic intrathecal treatment with baclofen, a GABABR agonist, significantly attenuated CIBP-induced mechanical allodynia and ambulatory pain. The expression levels of GABABRs were significantly decreased in a time-dependent manner and colocalized mostly with neurons and a minority with astrocytes and microglia. Chronic treatment with baclofen restored the expression of GABABRs and markedly inhibited the activation of cyclic adenosine monophosphate (cAMP)-dependent protein kinase and the cAMP-response element-binding protein signaling pathway. Our findings provide, to our knowledge, the first evidence that downregulation of GABABRs contribute to the development and maintenance of CIBP and restored diminished GABABRs attenuate CIBP-induced pain behaviors at least partially by inhibiting the protein kinase/cAMP-response element-binding protein signaling pathway. Therefore, spinal GABABR may become a potential therapeutic target for the management of CIBP.


Association between Nightlife Goers' Likelihood of an Alcohol Use Disorder and Their Preferred Bar's Closing Time: A Cross-Sectional Observational Study in Perth, Australia.
Associations between longer-term alcohol-related conditions and licensed outlet trading hours are not well understood. We investigated the association between nightlife-goers' likelihood of an alcohol use disorder (AUD) and their preference for bars with special permits to remain open 'late' (i.e., spent more time there compared to any other venue) until 2 a.m. or 3 a.m. (Friday; Saturday) or midnight (Sunday) compared to bars with 'standard' closing times of midnight (Friday; Saturday) or 10 p.m. (Sunday). A cross-sectional observational study was conducted in four major nightlife areas of Perth, Australia, in 2015-2016. We conducted weekend street intercept surveys outside bars between 8 p.m. and 3 a.m. and screened participants who reported alcohol use prior to the survey and spent more time in a bar than any other venue type (n = 667) regarding their past year drinking pattern using AUDIT-C (n = 459). We used gender-specific logistic regression models to estimate associations between AUDIT-C categories (1-4, low risk; 5-7, hazardous; 8-12, active AUD) and preference for bars with different closing times (late vs. standard). A large proportion of participants were hazardous drinkers or had active AUD (83% males; 65% females), and over half preferred a late to a standard closing bar. We found evidence of a positive association between preference for late closing bars and hazardous drinking females (OR = 3.48; 95% CI 1.47-8.23; p = 0.01), but not for females with active AUD, male hazardous drinkers, nor males with active AUD. Our study adds new evidence on associations between likelihood of AUD among nightlife-goers and trading hours. With increasing international relaxation of trading hours, evidence that late closing bars may be preferred by hazardous drinking females will be of concern to policymakers wanting to curb alcohol-related harms in the community.


Genomic characterisation of Escherichia coli isolates co-producing NDM-5 and OXA-1 from hospitalised patients with invasive infections.
Carbapenems are one of the last-report therapeutic choices to treat infections due to multidrug-resistant (MDR) micro-organisms. For this reason, the spread of carbapenemase-producing Enterobacteriaceae represents a serious health-public problem. Here we describe isolates co-producing blaNDM-5 and blaOXA-1. Three Escherichia coli isolates obtained from patients with invasive infections were analysed by phenotypic antibiotic susceptibility testing and whole-genome sequencing (WGS). All of the isolates were resistant to carbapenems, most β-lactam antibiotics, piperacillin/tazobactam, amoxicillin/clavulanic acid and ciprofloxacin, remaining susceptible to amikacin, fosfomycin, colistin and tigecycline. The isolates belonged to sequence types ST44, ST405 and ST167 and co-harboured the blaNDM-5 and blaOXA-1 genes. Two of the isolates also harboured extended-spectrum β-lactamase (ESBL) genes (blaCTX-M-15 and blaTEM-1b). The blaNDM-5 gene was probably carried chromosomally even if different plasmids were identified. Various virulence genes were also identified. Our results highlight that continuous surveillance is essential to monitor the spread of clinically important MDR pathogens.


The intracellular partitioning of trace metals in marine shellfish.
Marine organisms have evolved a number of metabolic strategies to deal with potentially toxic trace metals. To determine how "detoxification" mechanisms such as metal-binding proteins and concretions are involved in the intracellular partitioning of trace metals in marine shellfish, the oyster, Crassostrea virginica, and the blue crab, Callincetes sapidus, were exposed to controlled levels of trace metals. Oysters accumulated cadmium readily and produced specific low molecular weight, cadmium-binding proteins. Blue crabs produced a single cadmium-binding protein in the hepatopancreas and gills when exposed to cadmium through food or water, respectively. Concretions appear to be of limited importance in detoxification.


The effect of clomiphene citrate and estradiol on body weight, vaginal cornification, and uterine weight after chronic treatment of ovariectomized rats.
Clomiphene reduced the body weight gain of ovariectomized rats to a much greater degree than extradiol did. Estradiol had a more pronounced effect on vaginal cornification and uterine weight than clomiphene did.


Projection of new thresholds for hypertension to outpatient clinic patients and impact of risk factors: a cross-sectional study.
The 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines on hypertension management recommend new stage 1 hypertension thresholds (130-139/80-89 mmHg) for starting antihypertensive treatment. To analyze the impact of the 2017 ACC/AHA guidelines on patients' diagnoses within daily practice, in comparison with management using the 2018 European hypertension guidelines, regarding the new thresholds. Cross-sectional study conducted in a hypertension outpatient clinic at a tertiary-level public hospital. The diagnosis of hypertension was defined separately using each guideline. The participants were patients who were attending the hypertension clinic, who were evaluated using the thresholds of two guidelines, based on cardiovascular risk factors, including age, gender, smoking status, diabetes mellitus, dyslipidemia, obesity, osteoporosis, chronic renal failure and family history of hypertension. After adapting the guidelines to the blood pressure values of our sample, 74.5% (n = 277) of the patients were diagnosed as hypertensive according to the blood pressure classification of the European Society of Cardiology (ESC) guidelines published in 2018, while 91.1% (n = 339) of the patients were hypertensive according to the new 2017 ACC/AHA guidelines. Multivariate regression analysis revealed that the significant demographic and cardiovascular risk factors associated with hypertension, based on the 2018 European Society of Hypertension (ESH)/ESC guidelines, were age (odds ratio, OR: 1.027; 95% confidence interval, CI: 1.001-1.054; P = 0.042), obesity (OR: 4.534; 95% CI: 1.830-11.237; P = 0.001) and family history of hypertension (OR: 2.199; 95% CI: 1.252-3.862; P = 0.006). The factors associated with the definition of hypertension may vary through changing the threshold values.


Dialogue on analytical and ab initio methods in attoscience.
The perceived dichotomy between analytical and ab initio approaches to theory in attosecond science is often seen as a source of tension and misconceptions. This Topical Review compiles the discussions held during a round-table panel at the 'Quantum Battles in Attoscience' cecam virtual workshop, to explore the sources of tension and attempt to dispel them. We survey the main theoretical tools of attoscience-covering both analytical and numerical methods-and we examine common misconceptions, including the relationship between ab initio approaches and the broader numerical methods, as well as the role of numerical methods in 'analytical' techniques. We also evaluate the relative advantages and disadvantages of analytical as well as numerical and ab initio methods, together with their role in scientific discovery, told through the case studies of two representative attosecond processes: non-sequential double ionisation and resonant high-harmonic generation. We present the discussion in the form of a dialogue between two hypothetical theoreticians, a numericist and an analytician, who introduce and challenge the broader opinions expressed in the attoscience community.


Influence of the treatment of periodontal disease in serum concentration of sirtuin 1 and mannose-binding lectin.
Increased levels of periodontal pathogens disrupt the homeostasis between the host and its microbiota and increase susceptibility to periodontal diseases. Periodontitis increases the serum concentration of mannose-binding lectin (MBL), which exacerbates local inflammatory processes. In animal studies, sirtuin 1 (SIRT1) was associated with protection against inflammation. This study analyzed the influence of non-surgical periodontal treatment on serum levels of MBL and SIRT1. Forty patients with periodontitis and 38 periodontally healthy individuals (aged 45 to 79 years) were included. Periodontitis patients received scaling and root planing using machine driven and hand instruments. Clinical parameters, inflammatory biomarkers, MBL, and SIRT1 levels were measured at baseline and at post-treatment. For all patients, an inverse correlation was observed between serum concentrations of MBL and SIRT1 (r = -0.30; P = 0.006). Periodontal treatment reduced serum concentrations of MBL (1,099.35 ± 916.59 to 861.42 ± 724.82 ng/mL; P < 0.001) and C-reactive protein (6.05 ± 8.99 to 2.49 ± 2.89 mg/L; P = 0.009). By contrast, SIRT1 serum levels increased (1.06 ± 1.03 to 1.66 ± 1.64 ng/mL; P < 0.001) following periodontal treatment. Periodontal treatment was associated with decreased serum concentrations of MBL and CRP and increased serum levels of SIRT1. Prospective studies are needed to assess the impact of these biomarkers on pathophysiology of periodontitis.


Sequence analysis and crystal structure of a glycosylated protease from Euphorbia resinifera latex for its proteolytic activity aspect.
The investigation of a plant glycosylated serine protease (EuRP-61) isolated from Euphorbia resinifera latex for potential antiplatelet and anticoagulation activities has been previously reported. In the present study, the protein sequence and native crystal structure of EuRP-61 were characterized. The structure was identified using single-wavelength anomalous diffraction with a refinement resolution of 1.7 Å (PDB ID: 7EOX). The main structural components of EuRP-61 were composed of three domains: catalytic, protease-associated (PA), and fibronectin type III (Fn3)-like domains. The crystal structure revealed that some loops in the PA and catalytic domains of EuRP-61 were different from the other subtilisin-like proteases (cucumisin and SBT3). These different loops might be involved in the general monomer formation of EuRP-61, substrate specificity, and maintenance of the catalytic domain. The Fn3-like domain may provide flexibility to the enzyme to bind with various substrates and cell receptors. Additionally, the active site of EuRP-61 consisted of the catalytic triad of Ser434, His106, and Asp32, similar to other serine proteases. The present study provides additional information and insight into the protease and antithrombotic activities of EuRP-61, which could contribute to further development of this enzyme for biomedical treatment.


Patient with pseudo-retrograde coronary flow in the normal right coronary artery and left circumflex artery: pitfall of retrograde coronary flow to detect coronary artery occlusion.
A 75-year-old lady with hypertension and paroxysmal atrial fibrillation underwent echocardiography to evaluate cardiac function. Transthoracic Doppler echocardiography revealed retrograde coronary flow in the right coronary artery (RCA) and left circumflex artery (LCX). Computed tomographic coronary angiography demonstrated normal but tortuous coronary arteries. This tortuosity of the coronary arteries was thought be a cause of pseudo-retrograde coronary flow in the RCA and LCX. The present case demonstrates a pitfall of retrograde coronary flow for the detection of coronary artery occlusion in daily practice.


Immunoliposome encapsulation increases cytotoxic activity and selectivity of curcumin and resveratrol against HER2 overexpressing human breast cancer cells.
Natural compounds have been studied as a source of countless bioactive compounds with diverse activities. Among them, many dietary phytochemicals have been thoroughly studied for their cytotoxic or apoptotic effects in several cellular models in order to explain their anticancer capacity. Curcumin and resveratrol are two natural compounds with a large body of evidence showing their cytotoxic activity against a wide variety of cancer cells; however, their poor absorption, bioavailability, and low selectivity have limited their clinical use. With the aim of improving bioavailability and selectivity, the antiproliferative effects of free-, liposomed-, and immunoliposomed-curcumin and/or resveratrol formulations have been compared in two human breast cancer cell lines with different HER2 expression levels. The results demonstrate that when HER2-targeted immunoliposomes are coupled to trastuzumab there is a dramatic increase in the antiproliferative effects of curcumin and resveratrol in HER2 positive human breast cancer cells in comparison to regular liposomed or free forms, indicating an increase of its therapeutic effect. The enhancement of the cytotoxic effects was also correlated to the uptake of curcumin at intracellular level, as shown by using ImageStream technique. The striking efficacy of the immunoliposomed formulation containing both resveratrol and curcumin suggests a multitargeted mechanism of action that deserves further study. These findings show the potential of HER2-targeted nanovesicles to develop new drug delivery systems for cancer therapy based on these compounds and justify further preclinical trials.


Influence of temperature on ischemic brain: basic and clinical principles.
In the last decades, the interest in the association between body temperature and stroke outcome has reemerged, and the use of animal models has made it possible to know the underlying pathogenic mechanisms involved, most of them with pending confirmation in human clinics. In this work, we will review the effects of hyperthermia and hypothermia and its pathogenesis on ischemic stroke, and the evidence of the efficacy and safety of anti-hyperthermic and hypothermic treatments. We will describe how treatment of hyperthermia on ischemic stroke patients, improves patient comfort and outcome, both in the short and the long term, but new clinical studies are needed in this field. Despite the theoretical and experimental bases in favor of hypothermia for the treatment of brain ischemia, there is no definitive clinical evidence that has proved its benefits, so far. With current knowledge, an objective of a body temperature between 35.5 and 36.5 °C seems an optimal therapeutic target for both hyperthermic and normothermic patients.