Synthesis, expression and biological activity of the prohormone for gastrin releasing peptide (ProGRP).
Gastrin-releasing peptide (GRP) has a widespread distribution and multiple stimulating effects on endocrine and exocrine secretions and metabolism. The prohormone for GRP (ProGRP, 125 amino acids) is processed to the amidated, biologically active end products GRP(1-27) and GRP(18-27). Amidated forms of GRP are putative autocrine or paracrine growth factors in a number of cancers including colorectal cancer. However, the potential role and biological activity of proGRP has not been investigated. Using a newly developed antisera directed to the N terminus of human proGRP, proGRP immunoreactivity was detected in all of the endometrial, prostate, and colon cancer cell lines tested and in nine of 10 resected colorectal carcinomas. However, no amidated forms were detected, suggesting an attenuation of processing in tumors. Recombinant proGRP was expressed as a His-tag fusion protein and purified by metal affinity chromatography and HPLC. ProGRP stimulated proliferation of a colon cancer cell line and activated MAPK, but unlike GRP(18-27)amide had no effect on inositol phosphate production. ProGRP did not compete with iodinated bombesin in binding assays on Balb-3T3 cells transfected with the known GRP receptors, GRP-R or BRS-3. We conclude that proGRP is present in a number of cancer cell lines and in resected colorectal tumors and is biologically active. Our results suggest that antagonists to GRP precursors rather than the amidated end products should be developed as a treatment for colorectal and other cancers that express proGRP-derived peptides.


Recent Advances in Aggressive Large B-cell Lymphomas: A Comprehensive Review.
Diffuse large B-cell lymphoma (DLBCL) is an aggressive disease with considerable heterogeneity reflected in the 2008 World Health Organization classification. In recent years, genome-wide assessment of genetic and epigenetic alterations has shed light upon distinct molecular subsets linked to dysregulation of specific genes or pathways. Besides fostering our knowledge regarding the molecular complexity of DLBCL types, these studies have unraveled previously unappreciated genetic lesions, which may be exploited for prognostic and therapeutic purposes. Following the last World Health Organization classification, we have witnessed the emergence of new variants of specific DLBCL entities, such as CD30 DLBCL, human immunodeficiency virus-related and age-related variants of plasmablastic lymphoma, and EBV DLBCL arising in young patients. In this review, we will present an update on the clinical, pathologic, and molecular features of DLBCL incorporating recently gained information with respect to their pathobiology and prognosis. We will emphasize the distinctive features of newly described or emerging variants and highlight advances in our understanding of entities presenting a diagnostic challenge, such as T-cell/histiocyte-rich large B-cell lmphoma and unclassifiable large B-cell lymphomas. Furthermore, we will discuss recent advances in the genomic characterization of DLBCL, as they may relate to prognostication and tailored therapeutic intervention. The information presented in this review derives from English language publications appearing in PubMed throughout December 2015. For a complete outline of this paper, please visit: http://links.lww.com/PAP/A12.


[Drug-related problems in the emergency department observation area of a third-level hospital].
The therapeutic armamentarium of developed countries has experienced a great advance; however, increased drug therapy not only provides benefits, as the inappropriate use of drugs results in relevant consequences for patients. A 3-month, descriptive, cross-sectional, randomized study in 125 patients seen at the emergency department observation area of a third-level hospital to identify drug-related problems (DRPs). A hospital adaptation of Dader s method was used. A mean of 0.94 DRPs per patient was obtained. Major DRPs (mDRPs) represented 50% of all DRPs; 69.50% of DRPs were avoidable; 44% were moderate, 38% mild, and 18% serious; 54.4% of patients were admitted to hospital, which originated in a mDRP in 25% of cases--this represents 50% of all patients with a mDRP. A significant portion of patients admitted to the observation area present there as a result of a DRP.


Reply to the comment on "New insights into the biomineralization of mercury selenide nanoparticles through stable isotope analysis in giant petrel tissues" by A. Manceau, J. Hazard. Mater. 425 (2021) 127922. doi: 10.1016/j.jhazmat.2021.127922.
In the comments reported by A. Manceau [1], relating to our recent paper on mercury (Hg) species-specific isotopic characterization in giant petrel tissues [2] two critical questions were raised. Firstly, according to A. Manceau, our method of extraction and isolation of nanoparticles was not able to efficiently isolate mercury selenide nanoparticles (HgSe NPs) and therefore the δ202Hg values measured are not species-specific, but rather δ202Hg of mixtures of complexes such as MeHgCys, Hg(Sec)4, and HgSe. Secondly, he suggests that our main findings showing that no isotopic fractionation is induced during the HgSe NPs biomineralization step from the precursor-demethylated species is erroneous because it contradicts the conclusion of two recent articles by A. Manceau and co-workers [3,4]. In this reply we defend our scientific findings and respectively respond to the questions and comments raised by A. Manceau.


Insights from insulin resistance pathways: Therapeutic approaches against Alzheimer associated diabetes mellitus.
Alzheimer Associated Diabetes Mellitus, commonly known as Type 3 Diabetes Mellitus (T3DM) is a distinct subtype of diabetes with a pronounced association with Alzheimer's disease (AD). Insulin resistance serves as a pivotal link between these two conditions, leading to diminished insulin sensitivity, hyperglycemia, and impaired glucose uptake. The brain, a vital organ in AD context, is also significantly impacted by insulin resistance, resulting in energy deficits and neuronal damage, which are hallmark features of the neurodegenerative disorder. To pave the way for potential therapeutic interventions targeting the insulin resistance pathway, it is crucial to comprehend the intricate pathophysiology of T3DM and identify the overlapped features between diabetes and AD. This comprehensive review article aims to explore various pathway such as AMPK, PPARγ, cAMP and P13K/Akt pathway as potential target for management of T3DM. Through the analysis of these complex mechanisms, our goal is to reveal their interdependencies and support the discovery of innovative therapeutic strategies. The review extensively discusses several promising pharmaceutical candidates that have demonstrated dual drug action mechanisms, addressing both peripheral and cerebral insulin resistance observed in T3DM. These candidates hold significant promise for restoring insulin function and mitigating the detrimental effects of insulin resistance on the brain. The exploration of these therapeutic options contributes to the development of innovative interventions that alleviate the burden of T3DM and enhance patient care.


Recognizing Trained and Untrained Obstacles around a Port Transfer Crane Using an Image Segmentation Model and Coordinate Mapping between the Ground and Image.
Container yard congestion can become a bottleneck in port logistics and result in accidents. Therefore, transfer cranes, which were previously operated manually, are being automated to increase their work efficiency. Moreover, LiDAR is used for recognizing obstacles. However, LiDAR cannot distinguish obstacle types; thus, cranes must move slowly in the risk area, regardless of the obstacle, which reduces their work efficiency. In this study, a novel method for recognizing the position and class of trained and untrained obstacles around a crane using cameras installed on the crane was proposed. First, a semantic segmentation model, which was trained on images of obstacles and the ground, recognizes the obstacles in the camera images. Then, an image filter extracts the obstacle boundaries from the segmented image. Finally, the coordinate mapping table converts the obstacle boundaries in the image coordinate system to the real-world coordinate system. Estimating the distance of a truck with our method resulted in 32 cm error at a distance of 5 m and in 125 cm error at a distance of 30 m. The error of the proposed method is large compared with that of LiDAR; however, it is acceptable because vehicles in ports move at low speeds, and the error decreases as obstacles move closer.


Single daily dose of allopurinol.
Allopurinol was administered to seven patients with gout to compare the effects of three different methods of administration. Allopurinol 100 mg given three times daily. Allopurinol given once daily as three 100 mg tablets. Allopurinol given once daily as a single 300 mg tablet. Allopurinol as a single dose in the morning gave as sustained control of plasma levels as did divided administration.


A Highly Porous Nonwoven Thermoplastic Polyurethane/Polypropylene-Based Triboelectric Nanogenerator for Energy Harvesting by Human Walking.
: A highly porous nonwoven thermoplastic polyurethane (TPU)/Polypropylene (PP) triboelectric nanogenerator (N-TENG) was developed. To fabricate the triboelectric layers, the TPU nanofiber was directly electrospun onto the nonwoven PP at different basis weights (15, 30, and 50 g/m2). The surface morphologies and porosities of the nonwoven PP and TPU nanofiber mats were characterized by field-emission scanning electron microscopy and porosimetry. The triboelectric performance of the nonwoven TPU/PP based TENG was found to improve with an increase in the basis weight of nonwoven PP. The maximum output voltage and current of the TPU/PP N-TENG with 50% PP basis weight reached 110.18 ± 6.06 V and 7.28 ± 0.67 µA, respectively, due to high air volume of nonwoven without spacers. In order to demonstrate its practical application as a generator, a TPU/PP N-TENG-attached insole for footwear was fabricated. The N-TENG was used as a power source to turn on 57 light-emitting diodes through human-walking, without any charging system. Thus, owing to its excellent energy-conversion performance, simple fabrication process, and low cost, the breathable and wearable nonwoven fiber-based TENG is suitable for large-scale production, to be used in wearable devices.


Fossil Sirenia from the Pleistocene of Qatar: new questions about the antiquity of sea cows in the Gulf Region.
One of the largest and least documented populations of dugongs (Dugong dugon) resides in the coastal waters of the United Arab Emirates, and waters surrounding Saudi Arabia, Bahrain, and Qatar. The archaeological record of dugongs in the Gulf Region is abundant, but little is known about their fossil record in the region. Here we report an isolated sirenian rib fragment from the Futaisi Member of the Fuwayrit Formation near the town of Al Ruwais, in northern Qatar. The Fuwayrit Formation is a marine Pleistocene deposit exposed onshore in Qatar and the United Arab Emirates. Based on the correlative dating of the basal Futaisi Member with other onshore platforms, the rib fragment is approximately 125 ka. We propose that this isolated rib (likely the first rib from the right side) belongs to Dugongidae, with strong similarities to extant Dugong. We cannot, however, eliminate the possibility that it belongs to an extinct taxon, especially given its similarities with other fossil dugongid material from both Qatar and elsewhere in the world. Aside from reflecting the presence of Gulf seagrass communities in the Pleistocene, this occurrence also suggests that different (and potentially multiple) lineages of sirenians inhabited the Gulf Region in the geologic past.


Sensorimotor Rhythm-Brain Computer Interface With Audio-Cue, Motor Observation and Multisensory Feedback for Upper-Limb Stroke Rehabilitation: A Controlled Study.
Several studies have shown the positive clinical effect of brain computer interface (BCI) training for stroke rehabilitation. This study investigated the efficacy of the sensorimotor rhythm (SMR)-based BCI with audio-cue, motor observation and multisensory feedback for post-stroke rehabilitation. Furthermore, we discussed the interaction between training intensity and training duration in BCI training. Twenty-four stroke patients with severe upper limb (UL) motor deficits were randomly assigned to two groups: 2-week SMR-BCI training combined with conventional treatment (BCI Group, BG, n = 12) and 2-week conventional treatment without SMR-BCI intervention (Control Group, CG, n = 12). Motor function was measured using clinical measurement scales, including Fugl-Meyer Assessment-Upper Extremities (FMA-UE; primary outcome measure), Wolf Motor Functional Test (WMFT), and Modified Barthel Index (MBI), at baseline (Week 0), post-intervention (Week 2), and follow-up week (Week 4). EEG data from patients allocated to the BG was recorded at Week 0 and Week 2 and quantified by mu suppression means event-related desynchronization (ERD) in mu rhythm (8-12 Hz). All functional assessment scores (FMA-UE, WMFT, and MBI) significantly improved at Week 2 for both groups (p < 0.05). The BG had significantly higher FMA-UE and WMFT improvement at Week 4 compared to the CG. The mu suppression of bilateral hemisphere both had a positive trend with the motor function scores at Week 2. This study proposes a new effective SMR-BCI system and demonstrates that the SMR-BCI training with audio-cue, motor observation and multisensory feedback, together with conventional therapy may promote long-lasting UL motor improvement. Clinical Trial Registration: [http://www.chictr.org.cn], identifier [ChiCTR2000041119].


Regulation of MUC5AC mucin secretion and airway surface liquid metabolism by IL-1beta in human bronchial epithelia.
Mucociliary transport in the airways significantly depends on the liquid and mucin components of the airway surface liquid (ASL). The regulation of ASL water and mucin content during pathological conditions is not well understood. We hypothesized that airway epithelial mucin production and liquid transport are regulated in response to inflammatory stimuli and tested this hypothesis by investigating the effects of the pleiotropic, early-response cytokine, IL-1beta, on cultured primary human bronchial epithelial and second-passage, normal human tracheo-bronchial epithelial (NHTBE) cell cultures. Fully differentiated NHTBE cultures secreted two major airway mucins, MUC5AC and MUC5B. IL-1beta, in a dose- and time-dependent manner, increased the secretion of MUC5AC, but not MUC5B. MUC5AC mRNA levels were only transiently increased at 1 and 4 h after the start of IL-1beta treatment and returned to control levels thereafter, even though MUC5AC mucin production remained elevated for at least 72 h. Synchronous with elevated MUC5AC secretion, ASL volume increased, its percentage of solid was reduced, and the pH/[HCO(3)(-)] of the ASL was elevated. ASL volume changes reflected altered ion transport, including an upregulation of Cl(-) secretory currents (via CFTR and Ca(2+)-activated Cl(-) conductance) and an inhibition of epithelial sodium channel (ENaC)-mediated absorptive Na(+) currents. IL-1beta increased CFTR mRNA levels without affecting those for ENaC subunits. The synchronous regulation of ASL mucin and liquid metabolism triggered by IL-1beta may be an important defense mechanism of the airway epithelium to enhance mucociliary clearance during airway inflammation.


The Local Regulation of Vascular Function: From an Inside-Outside to an Outside-Inside Model.
Our understanding of the regulation of vascular function, specifically that of vasomotion, has evolved dramatically over the past few decades. The classic conception of a vascular system solely regulated by circulating hormones and sympathetic innervation gave way to a vision of a local regulation. Initially by the so-called, autacoids like prostacyclin, which represented the first endothelium-derived paracrine regulator of smooth muscle. This was the prelude of the EDRF-nitric oxide age that has occupied vascular scientists for nearly 30 years. Endothelial cells revealed to have the ability to generate numerous mediators besides prostacyclin and nitric oxide (NO). The need to classify these substances led to the coining of the terms: endothelium-derived relaxing, hyperpolarizing and contracting factors, which included various prostaglandins, thromboxane A2, endothelin, as well numerous candidates for the hyperpolarizing factor. The opposite layer of the vascular wall, the adventitia, eventually and for a quite short period of time, enjoyed the attention of some vascular physiologists. Adventitial fibroblasts were recognized as paracrine cells to the smooth muscle because of their ability to produce some substances such as superoxide. Remarkably, this took place before our awareness of the functional potential of another adventitial cell, the adipocyte. Possibly, because the perivascular adipose tissue (PVAT) was systematically removed during the experiments as considered a non-vascular artifact tissue, it took quite long to be considered a major source of paracrine substances. These are now being integrated in the vast pool of mediators synthesized by adipocytes, known as adipokines. They include hormones involved in metabolic regulation, like leptin or adiponectin; classic vascular mediators like NO, angiotensin II or catecholamines; and inflammatory mediators or adipocytokines. The first substance studied was an anti-contractile factor named adipose-derived relaxing factor of uncertain chemical nature but possibly, some of the relaxing mediators mentioned above are behind this factor. This manuscript intends to review the vascular regulation from the point of view of the paracrine control exerted by the cells present in the vascular environment, namely, endothelial, adventitial, adipocyte and vascular stromal cells.


Pancreatic imaging: current and emerging technologies.
This review discusses the current imaging modalities for the diagnosis and staging of solid and cystic pancreatic lesions and for the assessment of acute and chronic pancreatitis, and the future role of emerging technologies in the management of pancreatic diseases. Multidetector row spiral computed tomography is superior to conventional single-detector row spiral computed tomography in the detection and staging of pancreatic adenocarcinoma. Positron emission tomography is a sensitive but relatively nonspecific diagnostic modality. Positron emission tomography-computed tomography fusion may improve the staging accuracy for pancreatic cancer. Echo-enhanced ultrasound may have an emerging role in evaluating pancreatic masses. Endoscopic ultrasound with fine needle aspiration for cytology is the single best method for diagnosis and staging of nonmetastatic pancreatic cancer with a high accuracy for determining tumor resectability. In acute pancreatitis, a modification of the standard computed tomography severity index, which places greater emphasis on extrapancreatic complications, has shown superior correlation with various patient outcome measures. Endoscopic retrograde cholangiopancreatography is still the test of choice for morphological evaluation of chronic pancreatitis, whereas magnetic resonance cholangiopancreatography offers a noninvasive alternative in selected patients. Endoscopic ultrasound can be useful for detecting early chronic pancreatitis. Secretin-stimulated imaging techniques may eventually provide a noninvasive method of reliably assessing pancreatic exocrine function.


Proliferation-attenuating and apoptosis-inducing effects of tryptanthrin on human chronic myeloid leukemia K562 cell line in vitro.
Tryptanthrin, a kind of indole quinazoline alkaloid, has been shown to exhibit anti-microbial, anti-inflammation and anti-tumor effects both in vivo and in vitro. However, its biological activity on human chronic myeloid leukemia cell line K562 is not fully understood. In the present study, we investigated the proliferation-attenuating and apoptosis-inducing effects of tryptanthrin on leukemia K562 cells in vitro and explored the underlying mechanisms. The results showed that tryptanthrin could significantly inhibit K562 cells proliferation in a time- and dose-dependent manner as evidenced by MTT assay and flow cytometry analysis. We also observed pyknosis, chromatin margination and the formation of apoptotic bodies in the presence of tryptanthrin under the electron microscope. Nuclei fragmentation and condensation by Hoechst 33258 staining were detected as well. The amount of apoptotic cells significantly increased whereas the mitochondrial membrane potential decreased dramatically after tryptanthrin exposure. K562 cells in the tryptanthrin treated group exhibited an increase in cytosol cyt-c, Bax and activated caspase-3 expression while a decrease in Bcl-2, mito cyt-c and pro-caspase-3 contents. However, the changes of pro-caspase-3 and activated caspase-3 could be abolished by a pan-caspase inhibitor ZVAD-FMK. These results suggest that tryptanthrin has proliferation-attenuating and apoptosis-inducing effects on K562 cells. The underlying mechanism is probably attributed to the reduction in mitochondria membrane potential, the release of mito cyt-c and pro-caspase-3 activation.


Construction of arsenic-metal complexes loaded nanodrugs for solid tumor therapy: A mini review.
Arsenic trioxide (As2O3), a front-line therapeutic agent against acute promyelocytic leukemia, has a broad spectrum against malignancies. Unfortunately, the clinical application of As2O3 in treating hematological cancers has not been transformed to solid tumors, for its dose-limited toxicity and undesirable pharmacokinetics. The ordinary As2O3 loaded nanodrugs (such as liposomes, polymer micelles, albumin-based nanodrugs, and silica-based nanodrugs, etc.) still could not fuel up pharmaceuticals and eradicate toxicity for low delivery efficiency caused by the instability and severe drug leakage of formulations during circulation. Recently, the approach of forming and delivering arsenic-metal complexes which will dissociate in the tumoral environment caught our mind. This is the most effective strategy to reduce drug leakage in circulation and accumulate arsenite ions in tumor sites, therefore promote the anti-tumor effect and lighten the toxicity of the drug. This review aims to explain the formation mechanism of arsenic-metal nanocomposites and summarize the constructing strategies of the arsenic-metal nanocomplexes (arsenic-nickel, arsenic-manganese, arsenic-platinum, arsenic-gadolinium, arsenic-zinc, and arsenic-iron nanobins) loaded nanodrugs for solid tumor therapy. Furthermore, the expectations and challenges of arsenic-metal complexes containing nanodrugs for cancer therapy in the future were discussed.


Visualizing the effects of rTMS in a patient sample: small N vs. group level analysis.
The use of transcranial magnetic stimulation (TMS) to assess changes in cortical excitability is a tool used with increased prevalence in healthy and impaired populations. One factor of concern with this technique is how to achieve adequate statistical power given constraints of a small number of subjects and variability in responses. This paper compares a single pulse excitability measure using traditional group-level statistics vs single subject analyses in a patient population of subjects with focal hand dystonia, pre and post repetitive TMS (rTMS). Results show significant differences in cortical excitability for 4/5 subjects using a split middle line analysis on plots of individual subject data. Group level statistics (ANOVA), however, did not detect any significant findings. The consideration of single subject statistics for TMS excitability measures may assist researchers in describing the variably of rTMS outcome measures.


Development and evaluation of an algorithm to link mothers and infants in two US commercial healthcare claims databases for pharmacoepidemiology research.
Administrative healthcare claims databases are used in drug safety research but are limited for investigating the impacts of prenatal exposures on neonatal and pediatric outcomes without mother-infant pair identification. Further, existing algorithms are not transportable across data sources. We developed a transportable mother-infant linkage algorithm and evaluated it in two, large US commercially insured populations. We used two US commercial health insurance claims databases during the years 2000 to 2021. Mother-infant links were constructed where persons of female sex 12-55 years of age with a pregnancy episode ending in live birth were associated with a person who was 0 years of age at database entry, who shared a common insurance plan ID, had overlapping insurance coverage time, and whose date of birth was within ± 60-days of the mother's pregnancy episode live birth date. We compared the characteristics of linked vs. non-linked mothers and infants to assess similarity. The algorithm linked 3,477,960 mothers to 4,160,284 infants in the two databases. Linked mothers and linked infants comprised 73.6% of all mothers and 49.1% of all infants, respectively. 94.9% of linked infants' dates of birth were within ± 30-days of the associated mother's pregnancy episode end dates. Characteristics were largely similar in linked vs. non-linked mothers and infants. Differences included that linked mothers were older, had longer pregnancy episodes, and had greater post-pregnancy observation time than mothers with live births who were not linked. Linked infants had less observation time and greater healthcare utilization than non-linked infants. We developed a mother-infant linkage algorithm and applied it to two US commercial healthcare claims databases that achieved a high linkage proportion and demonstrated that linked and non-linked mother and infant cohorts were similar. Transparent, reusable algorithms applied to large databases enable large-scale research on exposures during pregnancy and pediatric outcomes with relevance to drug safety. These features suggest studies using this algorithm can produce valid and generalizable evidence to inform clinical, policy, and regulatory decisions.


The C-type lectin OCILRP2 costimulates EL4 T cell activation via the DAP12-Raf-MAP kinase pathway.
OCILRP2 is a typical Type-II transmembrane protein that is selectively expressed in activated T lymphocytes, dendritic cells, and B cells and functions as a novel co-stimulator of T cell activation. However, the signaling pathways underlying OCILRP2 in T cell activation are still not completely understood. In this study, we found that the knockdown of OCILRP2 expression with shRNA or the blockage of its activity by an anti-OCILRP2 antagonist antibody reduced CD3/CD28-costimulated EL4 T cell viability and IL-2 production, inhibit Raf1, MAPK3, and MAPK8 activation, and impair NFAT and NF-κB transcriptional activities. Furthermore, immunoprecipitation results indicated that OCILRP2 could interact with the DAP12 protein, an adaptor containing an intracellular ITAM motif that can transduce signals to induce MAP kinase activation for T cell activation. Our data reveal that after binding with DAP12, OCILRP2 activates the Raf-MAP kinase pathways, resulting in T cell activation.


[Methods of the videoendoscopic correction of the ureters strictures].
a retrospective analysis of the results of patients treatment with ureteral strictures by evaluating the effectiveness of various methods of laparoscopic operations. a retrospective analysis of the treatment of 30 patients operated in the Central Hospital of Civil Aviations from 2013 to the present time with strictures of all departments of the ureters, except the pelvic-ureteral segment (LMS), was performed. The study included 18 women and 12 men. The age of patients was 54+/-8.1 years (29-79 years) for men and 51+/-8.5 years (28-74 years) for women. According to the results of x-ray examinations, the length of ureter stricture was determined, after that selected the tactics of surgical treatment. The study included patients who underwent intestinal plastics of the ureter, the operation Boari, ureterocystoanastomosis, ureteroureterostomy. All stages of surgical interventions were performed laparoscopically. 23 patients (76.66%) had a smooth postoperative period. A month after the operation, ureteral stents were removed. Attacks of acute pyelonephritis, relapses of the disease were not observed during the follow-up period from 7 months to 3 years. Possible complications are analyzed. In one case, after intestinal plastic surgery of the ureter in the postoperative period, the phenomena of small bowel obstruction were noted, which required surgical treatment in the volume of applying a bypass eunoascendoanastomosis "side by side". In 7 cases, anastomosis strictures were diagnosed in the postoperative period. In the 5 cases, after examination (CT of the urinary tract with contrast, antegrade ureteropyelography), the anastomosis was recognized compensated. It is shown that all the necessary range of operations can be performed by laparoscopic method while preserving all the advantages of low-trauma access.


Molecular and biochemical characteristics of the inulosucrase HugO from Streptomyces viridochromogenes DSM40736 (Tü494).
Polyfructans are synthesized from sucrose by plants (mostly inulin) and by both Gram-negative and Gram-positive bacteria (mostly levan). In the phylum Actinobacteria only levan synthesis by Actinomyces species has been reported. We have identified a putative fructansucrase gene (hugO) in Streptomyces viridochromogenes DSM40736 (Tü494). HugO was heterologously expressed and biochemically characterized. HPSEC-MALLS and 2D-1H-13C nuclear magnetic resonance (NMR) spectroscopy analysis showed that the fructan polymer produced in vitro has an Molecular Weight of 2.5*107 Da and is an inulin that is mainly composed of (β2-1)-linked fructose units. This is the first report of a fructansucrase from Streptomyces and an inulosucrase from Actinobacteria. Database searches showed that fructansucrases clearly occur more widely in streptomycetes. Analysis of the active site of HugO and other actinobacterial Gram-positive fructansucrases revealed that their +1 substrate-binding sites are conserved, but are most similar to those in Gram-negative fructansucrases. HugO also resembles Gram-negative fructansucrases in not requiring calcium ions for activity. The origin and properties of HugO and other actinobacterial fructansucrases thus clearly differ from those of previously characterized Gram-positive fructansucrases.


Varying modalities of perinatal exposure to a pesticide cocktail elicit neurological adaptations in mice and zebrafish.
Epidemiological indications connect maternal and developmental presence or exposure to pesticides with an increased risk for a spectrum of neurological trajectories. To provide pre-clinical data in support of this hypothesis, we used two distinct experimental models. First, female and male mice were fed immediately prior to mating, and the resulting pregnant dams were continously fed during gestation and lactation periods using chow pellets containing a cocktail of six pesticides at tolerable daily intake levels. Male and female offspring were then tracked for behavioral and in vivo electrophysiological adaptations. Second, a zebrafish model allowed us to screen toxicity and motor-behavior outcomes specifically associated with the developmental exposure to a low-to-high concentration range of the cocktail and of each individual pesticide. Here, we report anxiety-like behavior in aging male mice maternally exposed to the cocktail, as compared to age and gender matched sham animals. In parallel, in vivo electrocorticography revealed a decrease in gamma (40-80 Hz) and an increase of theta (6-9 Hz) waves, delineating a long-term, age-dependent, neuronal slowing. Neurological changes were not accompanied by brain structural malformations. Next, by using zebrafish larvae, we showed an increase of all motor-behavioral parameters resulting from the developmental exposure to 10 μg/L of pesticide cocktail, an outcome that was not associated with midbrain structural or neurovascular modifications as assessed by in vivo 2-photon microscopy. When screening each pesticide, chlorpyrifos elicited modifications of swimming parameters at 0.1 μg/L, while other components provoked changes from 0.5 μg/L. Ziram was the single most toxic component inducing developmental malformations and mortality at 10 μg/L. Although we have employed non-equivalent modalities and timing of exposure in two dissimilar experimental models, these outcomes indicate that presence of a pesticide cocktail during perinatal periods represents an element promoting behavioral and neurophysiological modifications. The study limitations and the possible pertinence of our findings to ecotoxicology and public health are critically discussed.


Chondromyxoid fibroma of the skull base: a tumor which may be confused with chordoma and chondrosarcoma. A report of three cases and review of the literature.
Three cases of chondromyxoid fibroma arising in the skull base are reported. The tumors arose in females 34, 65, and 66 (median 55) years of age. Two women presented with headaches, and one with nasal obstruction. Radiographic studies revealed that all three lesions were expansile soft tissue masses centered in the clivus, at least 4 cm in greatest diameter. One lesion involved primarily the clivus, the others extended from the clivus into the sphenoid and ethmoid sinuses. Two of the three cases were initially misdiagnosed as chordoma or chondrosarcoma. The initial treatment was curettage of gross disease in all three cases. One patient also received radiation therapy. One patient had local progression of disease, which was treated with surgery and radiation therapy. All patients are clinically free of disease 11 to 26 months following the most recent treatment. Chondromyxoid fibroma can and should be distinguished from chondrosarcoma and chordoma, two tumors which more commonly arise in the skull base and which have the potential to metastasize.


[A limited sampling strategy of phenotyping probe midazolam to predict inhibited activities of hepatic CYP3A in rats].
The present study was to evaluate feasibility of a limited sampling strategy (LSS) in the prediction of inhibited hepatic CYP3A activity with systemic clearance of midazolam (MDZ), a hepatic CYP3A activity phenotyping probe. Rats were pretreated with a serial doses of ketoconazole, a selective inhibitor on CYP3A. Blood samples were collected and detected for MDZ at specified time points after intravenous injection of MDZ. Stepwise regression analysis and a Jack-knife validation procedures were performed in one group of rats as training set to establish the most informative LSS model for accurately estimating the clearance of MDZ. Another group of rats with same treatment was used as validation set to estimate the individual clearance based on predictive equations derived from the training set. Bland-Altman plots showed a good agreement between the systemic clearance calculated from DAS (CLobs) and corresponding parameter that was derived from three LSS models (CLest). LSS models derived from two or three sampling time points, including 60, 90 min, 30, 60, 90 min and 30, 60, 120 min, exhibited a good accuracy and acceptable error for estimating the CLobs of MDZ to evaluate hepatic CYP3A activity, especially the 60, 90 min LSS model is most accurate and convenient. The results supported that limited plasma sampling to predict the systemic clearance of MDZ is easier than the usual method for estimating CYP3A phenotyping when the hepatic activity of CYP3A is reduced in the rat. The present study provided theoretical basis and laboratory evidence for LSS to clinically evaluate metabolizing function of liver and


Effectiveness of Liraglutide in Type II Diabetes Mellitus Management: Experience in Emirati Patients.
To measure effectiveness of liraglutide in reducing glycated hemoglobin (HbA1C), weight, and systolic blood pressure (SBP) in Emirati patients. A retrospective cohort study. Endocrinology clinic in a 300-bed military hospital. A total of 152 patients who qualified for liraglutide between September 21, 2012, (first patient visit) and May 5, 2014 (last patient visit). Team collected demographic and clinical data using a standard form. Data keeper performed univariate analyses to measure the effect of liraglutide in reducing the three outcomes of interest; namely, HbA1C, weight, and SBP. One hundred patients had at least the first visit in the clinic and 98 patients came for a second follow-up visit while on the medication. Adherence of clinicians to the internal criteria for prescribing liraglutide was 92%. Patients' ages were 47.9 ± 11.7 years. Male-to-female ratio was almost 1:1. Overall, in the paired analyses, HbA1C decreased from first to second visits (8.7 ± 1.9 vs. 7.6 ± 1.8, P > 0.0001) and remained unchanged in subsequent visits (eg, in visit 3, HbA1C was 7.4 ± 1.8). Patients lost an average of 1.3 kg between the first and second visits (99.3 ± 19.3 vs. 98.0 ± 19.5, P = 0.0003). The reduction in SBP between visits 1 and 2 was less (130.9 ± 15.8 vs. 129.9 ± 16.5, P = 0.5896). ANOVA yielded a significant reduction in HbA1C at 4 months and 6 months (P values < 0.05). SBP dropped by about 3.6 mmHg and weight by about 2.3 kg (P values > 0.05). Liraglutide is effective in reducing HbA1C, weight, and to a lesser extent, SBP in Emirati patients.


Efficacy of a topical antibiotic irrigant in decreasing or eliminating bacterial contamination in surgical wounds.
Using a simple in vitro system, the authors showed that colony counts of Staphylococcus aureus, Staphylococcus epidermidis, Escherichia coli, and Pseudomonas species can be reduced by 12%-56% with saline irrigation; the reduction of colony numbers, however, especially for S. aureus, was not always statistically significant. However, even if it were statistically significant, the amount of reduction would not be clinically significant. A topical antibiotic irrigant containing bacitracin/neomycin was effective against S. aureus, S. epidermidis-, and E. coli-treated agar plates. Except for a single plate containing Pseudomonas organisms, the growth of Pseudomonas colonies was also prevented by antibiotic irrigation. Tissue samples of muscle, fat, and bone obtained during operation showed antibiotic levels comparable with, and in most cases greater than, those found in the blood agar plates. These data may be clinically significant and suggest that bacitracin/neomycin irrigation can be safely used to reduce the incidence of postoperative infection.


Physiological pathway of magnesium influx in rat ventricular myocytes.
Cytoplasmic free Mg(2+) concentration ([Mg(2+)]i) was measured in rat ventricular myocytes with a fluorescent indicator furaptra (mag-fura-2) introduced by AM-loading. By incubation of the cells in a high-K(+) (Ca(2+)- and Mg(2+)-free) solution, [Mg(2+)]i decreased from ? 0.9 mM to 0.2 to 0.5 mM. The lowered [Mg(2+)]i was recovered by perfusion with Ca(2+)-free Tyrode's solution containing 1 mM Mg(2+). The time course of the [Mg(2+)]i recovery was fitted by a single exponential function, and the first derivative at time 0 was analyzed as being proportional to the initial Mg(2+) influx rate. The Mg(2+) influx rate was inversely related to [Mg(2+)]i, being higher at low [Mg(2+)]i. The Mg(2+) influx rate was augmented by the high extracellular Mg(2+) concentration (5 mM), whereas it was greatly reduced by cell membrane depolarization caused by high K(+). Known inhibitors of TRPM7 channels, 2-aminoethoxydiphenyl borate (2-APB), NS8593, and spermine reduced the Mg(2+) influx rate with half inhibitory concentrations (IC50) of, respectively, 17 ?M, 2.0 ?M, and 22 ?M. We also studied Ni(2+) influx by fluorescence quenching of intracellular furaptra by Ni(2+). The Ni(2+) influx was activated by lowering intra- and extracellular Mg(2+) concentrations, and it was inhibited by 2-APB and NS8593 with IC50 values comparable with those for the Mg(2+) influx. Intracellular alkalization (caused by pulse application of NH4Cl) enhanced, whereas intracellular acidification (induced after the removal of NH4Cl) slowed the Mg(2+) influx. Under the whole-cell patch-clamp configuration, the removal of intracellular and extracellular divalent cations induced large inward and outward currents, MIC (Mg-inhibited cation) currents or IMIC, carried by monovalent cations likely via TRPM7 channels. IMIC measured at -120 mV was diminished to ? 50% by 100 ?M 2-APB or 10 ?M NS8593. These results suggest that TRPM7/MIC channels serve as a major physiological pathway of Mg(2+) influx in rat ventricular myocytes.


Generalizability theory distinguishes between state and trait anxiety.
Accurate distinction between state and trait anxiety is necessary for assessment and monitoring of individual anxiety levels over time and developing effective interventions to reduce anxiety. Generalizability theory (G-theory) is a suitable method to distinguish between state and trait and to evaluate reliability of test scores and sources of measurement error in the assessment of affective conditions. We applied G-theory to the widely used 40-item State and Trait Anxiety Inventory (STAI) completed by 139 participants on three occasions separated by 2-week intervals. The results show that both subscales of the STAI demonstrated excellent reliability for test scores in measuring trait anxiety with high generalizability of scores across occasions and persons (G = 0.84-0.92). The most dynamic aspects of state anxiety were identified in both subscales including satisfaction, nervousness, feelings of pleasure, perceived failure, calmness, feeling inadequate, and sensitivity to disappointments and this informed the development of a more sensitive state anxiety scale presented here. The STAI trait subscale and the proposed sensitive state subscale can be used to more accurately distinguish between state and trait anxiety. The most dynamic aspects of anxiety identified using G-theory are more amenable and need to be considered as the primary target of interventions aiming at reducing anxiety. More comprehensive assessment of state anxiety may benefit from the development of a longer scale informed by G-theory. (PsycInfo Database Record (c) 2021 APA, all rights reserved).


Prevalence and significance of left ventricular outflow gradient during dobutamine echocardiography.
This study investigated the clinical and physiological significance of the dynamic left ventricle outflow gradient observed in some patients during dobutamine stress echocardiography. Three hundred and ninety-four consecutive patients completed dobutamine stress echocardiography using Doppler echocardiography to assess the presence of myocardial ischaemia and left ventricular outflow gradient. The prevalence of left ventricular outflow gradient was evaluated and correlated with echocardiographic and clinical findings. Fifteen patients with left ventricular outflow gradient during dobutamine infusion underwent exercise echocardiography for appearance of left ventricular outflow gradient. Sixty-nine of 394 (17.5%) patients developed a left ventricular outflow gradient of more than 36 mmHg. In nine of them (13%) the anterior mitral valve leaflet had a systolic anterior motion. In 60 of the 69 patients (87%) there was a dynamic obstruction at the level of the papillary muscles. The mean intracavitary gradient was 75.4 (range 36-175) mmHg. There was no correlation between the presence or absence of a dobutamine stress echocardiography-induced left ventricle outflow gradient and chest pain or shortness of breath. In patients who developed a left ventricular outflow gradient ischaemic wall motion abnormalities occurred at a significantly lower frequency during dobutamine stress echocardiography (2.9 vs 16.4% P<0.001). None of the 15 patients who underwent exercise echocardiography developed significant left ventricular outflow gradient. Left ventricular outflow gradient occurs occasionally during dobutamine stress echocardiography examination. Its presence is of no physiological or clinical significance.


Comparison of tritiated thymidine labeling and suicide indices in acute nonlymphocytic leukemia.
Leukemic cells were obtained from the bone marrow or peripheral blood of patients with acute myelocytic leukemia or one of its variants. The tritiated thymidine labeling index of the leukemic cells and the suicide index of the cells that produce clusters in vitro were compared. The suicide index was 5 times greater than the labeling index (S.E.) [54 +/- 8% versus 12 +/- 3%], demonstrating the presence of a highly proliferative subpopulation of leukemic cells (in vitro colony-forming unit) among the relatively slowly proliferating leukemic cells. Since the leukemic in vitro colony-forming unit appears to be the progenitor of the recognizable leukemic cell population, the proliferative characteristics of the recognizable leukemic cells may not be reflective of that of leukemic stem cells.


Role of neonatal cerebrospinal fluid cytology in correlation to C-reactive protein, blood culture, risk factors and clinical outcomes in neonatal intensive care.
The number of neonatal cerebrospinal fluid (CSF) samples sent from the neonatal intensive care unit (NICU) for cytologic examination is rising, warranting accurate analysis and interpretation of the same. This study was taken up to assess the usefulness of CSF cell count and cytology in NICU settings, as it can be used even in a resource-limited setting. 1) To study the prevalence of cell count and cytologic changes in CSF from NICU and assess their usefulness in correlation to C-reactive protein, CSF neutrophil percentage, blood, CSF culture, and other biochemical parameters. 2) To correlate cell counts and cytology with age, period of gestation, presence, and absence of sepsis, seizures, intracranial hemorrhage, and their clinical follow-up. A retrospective study was done on neonatal CSF samples submitted for cytology over one year (January-December 2016) in the Department of Pathology. CSF cell counts were retrieved, and cytosmears were reviewed for cellularity, cell type, proportion, and background and correlated with the biochemical, microbiological, and clinicoradiological findings. A total of 213 samples were included with 140 males and 73 females with an age range of 0-28 (mean: 7.3) days. The mean CSF cell count was 5.48/cu.mm (0-90 cells/cu.mm). The most frequent cytologic finding was occasional lymphocytes or acellular CSF (63.9%). The CSF leucocyte count and protein levels showed a significant correlation with s C-reactive protein. The CSF cytology showed a significant correlation between the age of the neonate and blood neutrophil percentage (P = 0.0158). History of intracranial hemorrhage showed a significantly higher frequency of the presence of red blood cells (P = 0.0147). Accurate cell counts, cytology of neonatal CSF, and biochemical and microbiological workup can help diagnose and manage neonates in intensive care.


Biological Activity of Bursera schlechtendalii Essential oil and the Roles of Its Chemical Components in the Wound Healing Process.
Essential oils are composed of terpenes, some of which have properties related to healing. Bursera schlechtendalii essential oil (BSEO) is used to heal superficial wounds. However, there have been no studies verifying this property. The objectives of this study were to evaluate the healing activity of BSEO in a murine model and to propose the roles of its chemical components in this process. Healing activity was evaluated by an incision model, histological analysis was performed, and tensile strength and antibacterial activity were measured. The chemical composition of BSEO was determined by gas chromatography coupled with mass spectrometry (GC-MS), and the mechanisms of action of each chemical component during the phases of the healing process were proposed. In addition, acute dermal toxicity was evaluated. BSEO showed better wound closure at the macroscopic, histological, and tensile strength levels compared to controls and had an antibacterial effect. The major compound in BSEO was α-phellandrene. However, most of the monoterpenes identified in BSEO were in agreement with information found in the literature, so the possibility of synergy between the chemical components and their different targets in the healing process was schematically proposed. BSEO was shown to be safe in the dermal toxicity evaluation.


The ultrastructure of the tracheal epithelium in European common lizard (Lacerta agilis L.) and in sand lizard (Lacerta vivipara Jacq.).
This study describes the ultrastructure of the tracheal epithelium in the European Common lizard (Lacerta agilis L.) and in the Sand lizard (Lacerta vivipara Jacq .). The main attention is paid to the granular cells of secret-producing type, which form the substantial part of this epithelium and which were observed for the first time in the house gekko . Contrary to the findings in house gekko , in the representatives of the genus Lacerta 2 types of electrondense granules were observed. One type is homogeneous and lighter in colour, the other is darker with lamellar pattern. Among other elements, the ciliated cells as well as basal and plasmatic cells were found. In both species we also succeeded in proving the presence of isolated neurosecret -producing cells.


Comparison of cardiac output measures by transpulmonary thermodilution, pulse contour analysis, and pulmonary artery thermodilution during off-pump coronary artery bypass surgery: a subgroup analysis of the cardiovascular anaesthesia registry at a single tertiary centre.
Cardiac output measurement has a long history in haemodynamic management and many devices are now available with varying levels of accuracy. The purpose of the study was to compare the agreement and trending abilities of cardiac output, as measured by transpulmonary thermodilution and calibrated pulse contour analysis, using the VolumeView™ system, continuous thermodilution via a pulmonary artery catheter, and uncalibrated pulse contour analysis, using FloTrac™ with pulmonary artery bolus thermodilution. Twenty patients undergoing off-pump coronary artery bypass surgery using a pulmonary artery catheter and the VolumeView™ and FloTrac™ systems were included in this subgroup analysis of the cardiovascular anaesthesia registry at a single tertiary centre. During surgery, cardiac output was assessed after the induction of anaesthesia, after sternotomy, during the harvesting of grafts, during revascularization of the anterior and posterior/lateral wall, after protamine infusion, and after sternal fixation. In total, 145 sets of measurements were evaluated using Bland-Altman with % error calculation, correlation, concordance, and polar plot analyses. The percentage error (bias, limits of agreement) was 12.6 % (-0.12, -0.64 to 0.41 L/min), 26.7 % (-0.38, -1.50 to 0.74 L/min), 29.3 % (-0.08, -1.32 to 1.15 L/min), and 33.8 % (-0.05, -1.47 to 1.37 L/min) for transpulmonary thermodilution, pulmonary artery continuous thermodilution, calibrated, and uncalibrated pulse contour analysis, respectively, compared with pulmonary artery bolus thermodilution. All pairs of measurements showed significant correlations (p < 0.001), whereas only transpulmonary thermodilution revealed trending ability (concordance rate of 95.1 %, angular bias of 1.33°, and radial limits of agreement of 28.71°) compared with pulmonary artery bolus thermodilution. Transpulmonary thermodilution using the VolumeView™ system provides reliable data on cardiac output measurement and tracking the changes thereof when compared with pulmonary artery bolus thermodilution in patients with preserved cardiac function during off-pump coronary artery bypass surgery. Trial registration NCT01713192 (ClinicalTrials.gov).


Correlation Between High-Density Lipoprotein and Monocyte Subsets in Patients with Stable Coronary Heart Disease.
High-density lipoprotein (HDL) consists of heterogeneous particles with a variety of structures and functions. Its role in atherosclerosis has been gradually recognized. Studies have shown dysfunction of small HDL in patients with coronary artery disease (CAD). Monocytes play an important role in atherosclerosis, which can be divided into 3 subgroups based on the expression of surface markers CD14 and CD16. This study aimed to investigate the association between HDL and monocyte subsets in CAD patients. A total of 90 patients with stable CAD were selected in this study. Monocytes were divided into classical monocytes (CM, CD14++CD16-), intermediate monocytes (IM, CD14++CD16+), and non-classical monocytes (NCM, CD14+CD16++). HDL components in serum were determined by high-resolution polyacrylamide gel electrophoresis (detected by Quantimetrix HDL Lipoprint system, referring to HDL subfractions analysis: A new laboratory diagnostic assay for patients with cardiovascular diseases and dyslipoproteinemia). Serum level of small HDL was positively correlated with circulating proinflammatory NCM (r=0.30; p=0.004), negatively correlated with CM, and not correlated with IM. We also found that disease severity was not associated with diabetes mellitus, glycosylated hemoglobin, hypertension, smoking history, or statin dosage. Our study confirmed that small HDL level is associated with an increase in NCM and a decrease in CM, suggesting the proinflammatory relationship between small HDL and intrinsic immune function during the progression of stable CAD.


Human papillomavirus type 38 isolated from patients with epidermodysplasia verruciformis.
A new type of human papillomavirus (HPV), HPV-38b, was isolated from patients with epidermodysplasia verruciformis and was molecularly cloned. This HPV was shown by hybridization experiments to have almost no sequence homology with other types of reported HPVs, but did show homology with HPV-38, which was recently isolated from a melanoma. A physical map and a rough genetic map of the organization of this HPV are presented.


Iliac Artery-Inferior Vena Cava-Duodenal Fistula: An Unusual Cause of Massive Gastrointestinal Bleeding.
An arteriovenous-enteric fistula is a 3-way connection between the vascular and enteric system and associated with high mortality. We describe a case of iliac artery-inferior vena cava-duodenal fistula in a young female with a retroperitoneal mass presenting with sepsis and hemorrhagic shock with a catastrophic clinical course. These fistulas can be missed on endoscopy/colonoscopy and are usually diagnosed on computed tomography angiogram of the abdomen. Complex vasculoenteric fistula should be among differentials in patients presenting with gastrointestinal bleeding, especially with a history of malignancy, radiation, foreign bodies, and trauma. The management is complex and should involve a multidisciplinary approach involving vascular surgery, intervention radiology, and gastroenterologist.


Treatment with tenofovir disoproxil fumarate or entecavir in chronic hepatitis B virus-infected patients with renal impairment: results from a 7-year, multicentre retrospective cohort study.
Limited data exist regarding tenofovir disoproxil fumarate (TDF) safety and effectiveness in chronic hepatitis B virus-infected (CHB) patients with renal impairment (RI). To compare real-world data on renal safety and effectiveness of TDF vs entecavir (ETV) in CHB patients with moderate-to-severe RI. Retrospective, non-interventional, cohort study analysing medical records for TDF/ETV-treated CHB patients (54 European centres). Included patients experienced moderate-to-severe RI (creatinine clearance 20-60 mL/min [Cockcroft-Gault]) either before TDF/ETV initiation ('before' subgroup [baseline = treatment initiation]) or after TDF/ETV initiation ('after' subgroup [baseline = first RI occurrence]). The primary objective was TDF safety, particularly renal-related adverse events of special interest (AESI). TDF and ETV safety and effectiveness were compared and multivariate analyses were performed using inverse probability treatment weighting. 'Before' subgroup included 107 TDF- and 91 ETV-treated patients; 'after' subgroup included 212 TDF- and 77 ETV-treated patients. Mean baseline creatinine clearance was higher for TDF- vs ETV-treated patients (both subgroups). Median follow-up was 3.1 years (both treatments). AESI were more frequent with TDF vs ETV ('before': 18.7% vs 8.8%; 'after': 9.9% vs 3.9%); however, differences were not significant by multivariate analysis. Only TDF-treated patients experienced renal tubular dysfunction (6.5% 'before'; 1.9% 'after') as well as renal adverse events leading to treatment discontinuation (8.4% 'before'; 7.1% 'after'). Effectiveness was similar between treatments. Overall safety was similar for TDF vs ETV (both subgroups). Given that renal tubular dysfunction occurred with TDF and not with ETV, renal safety concerns may be greater with TDF in CHB patients with RI.


Numerical Study of Angle-Insensitive and Tunable Dual-Band THz Absorber Using Periodic Cross-Shaped Graphene Arrays.
A dual-band terahertz (THz) absorber using the periodic cross-shaped graphene arrays is presented. It is shown that the dual-band light absorption enhancement of graphene results from the edge graphene plasmon (EGP) resonance, and the locations of the two absorption peaks can be precisely estimated by using the Fabry-Pérot (F-P) cavity model. Slight residual reflection remains at the two absorption peaks because the input impedance of the cross-arm cannot be perfectly matched with the free space impedance. In addition, the locations of the two absorption bands can be simultaneously tuned by changing the Fermi level of graphene, and they can be independently tuned by changing the width or the length of the cross-arm of graphene. Excellent angle-insensitivity dual-band absorption enhancement of graphene can be maintained for both the transverse electric (TE) and transverse magnetic (TM) polarizations.


Listeria monocytogenes CadC Regulates Cadmium Efflux and Fine-tunes Lipoprotein Localization to Escape the Host Immune Response and Promote Infection.
Listeria monocytogenes is a major intracellular human foodborne bacterial pathogen. We previously revealed L. monocytogenes cadC as highly expressed during mouse infection. Here we show that L. monocytogenes CadC is a sequence-specific, DNA-binding and cadmium-dependent regulator of CadA, an efflux pump conferring cadmium resistance. CadC but not CadA is required for L. monocytogenes infection in vivo. Interestingly, CadC also directly represses lspB, a gene encoding a lipoprotein signal peptidase whose expression appears detrimental for infection. lspB overexpression promotes the release of the LpeA lipoprotein to the extracellular medium, inducing tumor necrosis factor α and interleukin 6 expression, thus impairing L. monocytogenes survival in macrophages. We propose that L. monocytogenes uses CadC to repress lspB expression during infection to avoid LpeA exposure to the host immune system, diminishing inflammatory cytokine expression and promoting intramacrophagic survival and virulence. CadC appears as the first metal efflux pump regulator repurposed during infection to fine-tune lipoprotein processing and host responses.


[Depression as a biopsychosocial problem].
The article discusses the role of biological and psychological adaptive and compensatory mechanisms in the aetiology and pathogenesis of affective disorders, the relationship between the genetic characteristics of an individual, which determine vulnerability, and epigenetic mechanisms dependent on external psychosocial influences. The role of psychological factors disrupted the consistency of mental functions and the preservation of individuality that determines the psychogenesis of the disease both at the borderline and at the psychotic level is indicated. The psychoprophylactic and therapeutic role of psychotherapy is substantiated with an analysis of its influence both on the biological parameters of the brain and on the psychological characteristics of an individual, including an assessment of the quality of life. A comprehensive biopsychosocial approach to a spectrum of affective disorders makes a significant contribution to the development of personalized person-centered medicine, considering the phenomenological characteristics of the disease, as well as the psychological characteristics of patients and the nature of their social adaptation, which increases the effectiveness of treatment and rehabilitation of mentally ill patients.


Loss in working years after a breast cancer diagnosis.
Breast cancer can negatively influence working life, but it is unclear how many working years women with breast cancer can expect to lose. Women diagnosed with breast cancer between 1997 and 2012 were identified in the Breast Cancer Data Base Sweden (N=19 661), together with breast cancer-free comparison women (N=81 303). Using flexible parametric survival modelling, the loss in working years was calculated as the difference in the remaining years in the work force between women with and without breast cancer. Women aged 50 years at diagnosis with stage I disease lost on average 0.5 years (95% CI, 0.2-0.7) of their remaining working time; the corresponding estimates were 0.9 years (0.5-1.2) in stage II, 2.5 years (1.9-3.1) in stage III and 8.1 years (6.5-9.7) in stage IV. Women with in situ breast cancer did not lose any working years. The strongest treatment determinant was axillary lymph node dissection. We found a loss in working years not only in late but also in early-stage breast cancer. Although it is reassuring that some groups had no or only a modest work loss, the economic consequences for society are considerable given the large number of women annually diagnosed with breast cancer.


Appearance of 1-2 Mbp giant DNA fragments as an early common response leading to cell death induced by various substances that cause oxidative stress.
The effects of oxidative stress on double strand DNA breakage were examined in T-24 human bladder tumor cells using various active oxygen producing agents such as hydrogen peroxide (H2O2), bleomycin (BLM), neocarzinostatin (NCS), and x-ray irradiation. Analysis of the DNA by pulsed-field gel electrophoresis (PFGE) revealed that discrete giant DNA fragments of 1-2 Mbp and 200-800 kbp had accumulated in the nuclei of the treated cells. The 1-2 Mbp giant DNA fragments were first observed 2 h after the T-24 cells were exposed to the active oxygen producing agents, or irradiated with x-ray. The appearance and the amounts of 1-2 Mbp and 200-800 kbp giant DNA fragments seemed to depend on the concentration and the type of reagents used or the dose of x-ray. Following the accumulation of giant DNA fragments, another type of DNA fragmentation was detected and DNA fragments smaller than 100 kbp accumulated in the nuclei of the cells irradiated with x-ray or treated with NCS. In addition, DNA ladder formation, which is characteristic of apoptosis, was observed. The giant DNA fragments appeared to arise as a consequence of double-stranded DNA breakage, which occurred earlier than cell lysis, as assessed by 51Cr release. These findings indicate that the formation of giant DNA fragments is a specific characteristic of cells responding to oxidative stress, and it may be an initial event that leads to cell death.


Remodeling the Th1 polarized systemic environment contributes to neurogenesis and cognitive function via the Wnt7a pathway in neonatal mice.
Neonatal Bacillus Calmette-Guérin (BCG) vaccination results in a positive effect on hippocampal neurogenesis and cognition. Serum cytokines are considered to be the chief culprit. In this study, serum from BCG-treated mice was identified as Th1 polarized serum. The serum showed an increased ratio of IFN-γ to IL-4 and decreased levels of TNF-α and IL-6. After Th1 polarized serum was injected intraperitoneally into postnatal mice, the levels of cytokines and ratio of IFN-γ to IL-4 in the serum and hippocampus of postnatal mice showed a similar alteration as those in Th1 polarized serum. This result indicated that the immune homeostatic milieu in postnatal mice was broken and the Th1 polarized systemic environment in the BCG-serum group was remodeled. The BCG-serum group displayed more BrdU+/DCX+ cells, BrdU+/NeuN+ cells, Nestin+ cells and better cognitive abilities. In neural stem cells, the Wnt7a/β-catenin signaling pathway was activated and exposure to the Wnt7a antagonist Dickkopf-1 inhibited BCG-serum-induced Wnt7a/β-catenin signaling, neurogenesis and cognitive function. Additionally, BCG-serum was associated with elevations in hippocampal brain-derived neurotrophic factor (BDNF) levels, and BDNF expression in the BCG-serum group was offset by Dickkopf-1 treatment. By rebalancing the Th1 polarized systemic environment in neonatal mice, it is possible that treatment with BCG-serum promotes hippocampal neurogenesis and improves cognitive functions, which are associated with Wnt7a/β-catenin-BDNF signaling.


Discovery and optimization of C-2 methyl imidazopyrrolopyridines as potent and orally bioavailable JAK1 inhibitors with selectivity over JAK2.
Herein we report the discovery of the C-2 methyl substituted imidazopyrrolopyridine series and its optimization to provide potent and orally bioavailable JAK1 inhibitors with selectivity over JAK2. The C-2 methyl substituted inhibitor 4 exhibited not only improved JAK1 potency relative to unsubstituted compound 3 but also notable JAK1 vs JAK2 selectivity (20-fold and >33-fold in biochemical and cell-based assays, respectively). Features of the X-ray structures of 4 in complex with both JAK1 and JAK2 are delineated. Efforts to improve the in vitro and in vivo ADME properties of 4 while maintaining JAK1 selectivity are described, culminating in the discovery of a highly optimized and balanced inhibitor (20). Details of the biological characterization of 20 are disclosed including JAK1 vs JAK2 selectivity levels, preclinical in vivo PK profiles, performance in an in vivo JAK1-mediated PK/PD model, and attributes of an X-ray structure in complex with JAK1.


Molecular dynamics simulation of the ionic liquid N-ethyl-N,N-dimethyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl)imide.
Thermodynamics, structure, and dynamics of an ionic liquid based on a quaternary ammonium salt with ether side chain, namely, N-ethyl-N,N-dimethyl-N-(2-methoxyethyl)ammonium bis(trifluoromethanesulfonyl)imide, MOENM2E TFSI, are investigated by molecular dynamics (MD) simulations. Average density and configurational energy of simulated MOENM2E TFSI are interpreted with models that take into account empirical ionic volumes. A throughout comparison of the equilibrium structure of MOENM2E TFSI with previous results for the more common ionic liquids based on imidazolium cations is provided. Several time correlation functions are used to reveal the microscopic dynamics of MOENM2E TFSI. Structural relaxation is discussed by the calculation of simultaneous space-time correlation functions. Temperature effects on transport coefficients (diffusion, conductivity, and viscosity) are investigated. The ratio between the actual conductivity and the estimate from ionic diffusion by the Nernst-Einstein equation indicates that correlated motion of neighboring ions in MOENM2E TFSI is similar to imidazolium ionic liquids. In line with experiment, Walden plot of conductivity and viscosity indicates that simulated MOENM2E TFSI should be classified as a poor ionic liquid.


Development and Validation of a Liquid Chromatography-Tandem Mass Spectrometry Method for the Quantitation of Microcystins in Blue-Green Algal Dietary Supplements.
A liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed for the simultaneous detection and quantitation of seven microcystin congeners (1-7) and nodularin-R (8) in blue-green algal dietary supplements. Single-laboratory method validation data were collected in four supplement matrices (capsule, liquid, powder, and tablet) fortified at toxin concentrations from 0.25-2.00 μg/g (ppm). Average recoveries and relative standard deviations (RSD) using matrix-corrected solvent calibration curves were 101% (6% RSD) for all congeners and supplements investigated. Limits of detection (0.006-0.028 μg/g) and quantitation (0.018-0.084 μg/g) were sufficient to confirm the presence of microcystin contamination at the Oregon-mandated guidance concentration of 1.0 μg of microcystin-LReq/g. Quantitated concentrations of microcystin contamination in market-available Aphanizomenon flos-aquae blue-green algal supplements ranged from 0.18-1.87 μg of microcystin-LReq/g for detected congeners microcystin-LR, microcystin-LA, and microcystin-LY (3-5). Microcystin-RR, -YR, -LW, and -LF and nodularin-R (1, 2, and 6-8) were not detected in the supplements examined.


An Improved Approach for RSSI-Based only Calibration-Free Real-Time Indoor Localization on IEEE 802.11 and 802.15.4 Wireless Networks.
Assuming a reliable and responsive spatial contextualization service is a must-have in IEEE 802.11 and 802.15.4 wireless networks, a suitable approach consists of the implementation of localization capabilities, as an additional application layer to the communication protocol stack. Considering the applicative scenario where satellite-based positioning applications are denied, such as indoor environments, and excluding data packet arrivals time measurements due to lack of time resolution, received signal strength indicator (RSSI) measurements, obtained according to IEEE 802.11 and 802.15.4 data access technologies, are the unique data sources suitable for indoor geo-referencing using COTS devices. In the existing literature, many RSSI based localization systems are introduced and experimentally validated, nevertheless they require periodic calibrations and significant information fusion from different sensors that dramatically decrease overall systems reliability and their effective availability. This motivates the work presented in this paper, which introduces an approach for an RSSI-based calibration-free and real-time indoor localization. While switched-beam array-based hardware (compliant with IEEE 802.15.4 router functionality) has already been presented by the author, the focus of this paper is the creation of an algorithmic layer for use with the pre-existing hardware capable to enable full localization and data contextualization over a standard 802.15.4 wireless sensor network using only RSSI information without the need of lengthy offline calibration phase. System validation reports the localization results in a typical indoor site, where the system has shown high accuracy, leading to a sub-metrical overall mean error and an almost 100% site coverage within 1 m localization error.


[Adrenal insufficiency in patients with kidney failure secondary to amyloidosis. Its detection by a stimulation test].
In order to know the prevalence rate of adrenal insufficiency among patients with renal failure due to amyloidosis; we have performed a stimulation test with synthetic corticotropin hormone (Nuvacthen test) in nine patients diagnosed of renal amyloidosis and in five controls. We also measured ACTH and plasma cortisol levels. In two out of nine patients (22%) a low ACTH, low plasmatic cortisol and an abnormal response to Nuvacthen test were detected being diagnosed of primary adrenal insufficiency. We conclude that adrenal insufficiency is not an infrequent finding in systemic amyloidosis and may be due to secondary amyloidotic infiltration of adrenal or pituitary glands. Though Nuvacthen test is a useful test to diagnose subclinical adrenal insufficiency, in our series patients with an abnormal response also had low levels of basal cortisol and ACTH and no one patient with normal basal levels had an abnormal response to the stimulation test.


Hypercalcitoninaemia in a patient with urticaria pigmentosa. A possible cause of diarrhoea.
Mastocytosis gives rise to clinical symptoms such as flushing, itching and diarrhoea. We report a patient with urticaria pigmentosa without evidence of systemic involvement but with recurrent episodes of diarrhoea. The patient had elevated circulating levels of calcitonin, which might have been a mediator of her diarrhoea. We suggest that serum calcitonin level should be checked in patients with mast cell disease and diarrhoea.


To evaluate and compare the effect of different light-curing modes and different liners on cuspal deflection in premolar teeth restored with bulk filled or incrementally filled composite measured at different time intervals.
The aim of this study is to evaluate and to compare the effect of different light-curing modes and different liners on cuspal deflection in premolar teeth restored with bulk filled or incrementally filled composite measured at different time intervals. The study was divided into two parts (Part 1-different curing modes, Part 2-different liner) each with sixty extracted human upper premolar teeth with standardized large mesio-occlusal-distal cavities prepared. Each part was divided into two groups according to the composite used (Group A-Filtek Z350 XT, Group B-Sonic fill). Each group was then divided into three subgroups according to the light-curing modes (soft-start, pulse, and continuous curing mode) and liner (Filtek Z350 XT Flowable, Vitremer) used. The cuspal deflection was then measured with a digital micrometer gauge and subjected to statistically analysis using analysis of variance and Tukey's post hoc test. Sonic fill composite, resin-modified glass ionomer cement (RMGIC) liner and curing with soft-start/pulse curing mode had significantly lower cuspal deflection compared to Filtek Z350 XT, flowable liner, and continuous curing mode, respectively. Sonic fill composite, RMGIC liner under the restorations and composites cured with soft start/pulse curing mode resulted in reduced cuspal deflection.


A new type of gasochromic material: conducting polymers with catalytic nanoparticles.
We report the first observation of gasochromism for a material based on a thin film of polyaniline:polystyrene sulfonate/platinum nanoparticles (PANI:PSS/PtNPs). This novel material displayed a significant colour change, from green to pale yellow, when exposed to hydrogen. Our results show that the PtNPs trigger a reductive reaction on the polymer surface. This new mechanism dramatically expands the selection of available gasochromic materials.


Molecular dynamics study of water channels in natural and synthetic amyloid-β fibrils.
We compared all-atom explicit solvent molecular dynamics simulations of three types of Aβ(1-40) fibrils: brain-seeded fibrils (2M4J, with a threefold axial symmetry) and the other two, all-synthetic fibril polymorphs (2LMN and 2LMP, made under different fibrillization conditions). Fibril models were constructed using either a finite or an infinite number of layers made using periodic images. These studies yielded four conclusions. First, finite fibrils tend to unravel in a manner reminiscent of fibril dissolution, while infinite fibrils were more stable during simulations. Second, salt bridges in these fibrils remained stable in those fibrils that contained them initially, and those without salt bridges did not develop them over the time course of the simulations. Third, all fibrils tended to develop a "stagger" or register shift of β-strands along the fibril axis. Fourth and most importantly, the brain-seeded, 2M4J, infinite fibrils allowed bidirectional transport of water in and out of the central longitudinal core of the fibril by rapidly developing gaps at the fibril vertices. 2LMP fibrils also showed this behavior, although to a lesser extent. The diffusion of water molecules in the fibril core region involved two dynamical states: a localized state and directed diffusion in the presence of obstacles. These observations provided support for the hypothesis that Aβ fibrils could act as nanotubes. At least some Aβ oligomers resembled fibrils structurally in having parallel, in-register β-sheets and a sheet-turn-sheet motif. Thus, our findings could have implications for Aβ cytotoxicity, which may occur through the ability of oligomers to form abnormal water and ion channels in cell membranes.


Interactive balance training integrating sensor-based visual feedback of movement performance: a pilot study in older adults.
Wearable sensor technology can accurately measure body motion and provide incentive feedback during exercising. The aim of this pilot study was to evaluate the effectiveness and user experience of a balance training program in older adults integrating data from wearable sensors into a human-computer interface designed for interactive training. Senior living community residents (mean age 84.6) with confirmed fall risk were randomized to an intervention (IG, n = 17) or control group (CG, n = 16). The IG underwent 4 weeks (twice a week) of balance training including weight shifting and virtual obstacle crossing tasks with visual/auditory real-time joint movement feedback using wearable sensors. The CG received no intervention. Outcome measures included changes in center of mass (CoM) sway, ankle and hip joint sway measured during eyes open (EO) and eyes closed (EC) balance test at baseline and post-intervention. Ankle-hip postural coordination was quantified by a reciprocal compensatory index (RCI). Physical performance was quantified by the Alternate-Step-Test (AST), Timed-up-and-go (TUG), and gait assessment. User experience was measured by a standardized questionnaire. After the intervention sway of CoM, hip, and ankle were reduced in the IG compared to the CG during both EO and EC condition (p = .007-.042). Improvement was obtained for AST (p = .037), TUG (p = .024), fast gait speed (p = . 010), but not normal gait speed (p = .264). Effect sizes were moderate for all outcomes. RCI did not change significantly. Users expressed a positive training experience including fun, safety, and helpfulness of sensor-feedback. Results of this proof-of-concept study suggest that older adults at risk of falling can benefit from the balance training program. Study findings may help to inform future exercise interventions integrating wearable sensors for guided game-based training in home- and community environments. Future studies should evaluate the added value of the proposed sensor-based training paradigm compared to traditional balance training programs and commercial exergames. http://www.clinicaltrials.govNCT02043834.


Conservation of total T-cell counts during HIV infection: alternative hypotheses and implications.
While CD4+ T-cell counts in the blood of HIV-infected individuals gradually decrease, there is a parallel increase in the number of blood CD8+ T cells such that the total number of T cells remains essentially constant for several years (1). The basis and significance of this phenomenon are not known. Based on a statistical analysis of longitudinal T-cell counts from the Transfusion Safety Study (TSS) database and on theoretical considerations, we evaluate several alternative models, including versions of the "blind homeostasis" (BH) hypothesis (1-3). At issue is the nature of the homeostatic regulation of lymphocytes and its apparent failure in HIV infection. The most plausible explanation for the conservation of total blood T-cell numbers while subset ratios change is that CD4+ and CD8+ T cells compete for a limited access to the blood compartment. Such interaction between the subsets implies, in particular, that changes in the number of CD4+ T cells occurring in other tissues cannot be reliably inferred from those observed in the blood. We reiterate propositions made earlier (4) that much of the apparent "depletion" of CD4+ lymphocytes during the asymptomatic phase of HIV infection may be attributed to redistribution between the tissues and the blood compartment.


Macronutrients and colorectal cancer: a Swiss case-control study.
A role of energy and various nutrients, including protein, sugar, saturated and unsaturated fats, in colorectal cancer risk has been suggested, but should be better defined. The association between dietary intake of various macronutrients and colorectal cancer risk was analysed using data from a case-control study conducted between 1992 and 2000 in the Swiss Canton of Vaud. The study comprised 286 case subjects (174 males, 112 females; median age 65 years) with incident, histologically confirmed colon (n = 149) or rectal (n = 137) cancer, and 550 control subjects (269 males, 281 females; median age 59 years) admitted to the same University Hospital for a wide spectrum of acute non-neoplastic conditions. Dietary habits were investigated using a validated food frequency questionnaire, including questions on 79 foods or recipes and on individual fat intake pattern. Multivariate odds ratios (OR) were obtained after allowance for age, sex, education, physical activity and energy intake. The risk of colon and rectal cancer increased with total energy intake (OR in highest and lowest tertile, 2.0 and 2.2, respectively). There was no significant relation with starches or proteins, a significant inverse relation with sugars (OR for the highest tertile, 0.5), a direct trend in risk of borderline significance for saturated fats (OR = 1.4 for the highest tertile), and significant inverse trends for monounsaturated (OR = 0.6) and polyunsaturated fats (OR = 0.6). These findings confirm that energy intake is directly related to colorectal cancer risk, and that different types of fat may have different roles in colorectal carcinogenesis.


Asynchrony of primary tumor and mediastinal lymph nodes response after neoadjuvant immunotherapy plus chemotherapy in a patient with stage IIIA non-small-cell lung cancer: a case report.
With the rapid development of immunotherapy, the efficacy and feasibility of neoadjuvant immunotherapy for early resectable non-small-cell lung cancer (NSCLC) has been demonstrated. However, there are still difficulties and controversies in evaluating the efficacy of neoadjuvant immunotherapy. In our report, we described a 43-year-old female patient who was diagnosed with stage IIIA (cT1N2M0) pulmonary adenocarcinoma. After two cycles of neoadjuvant immunotherapy (sintilimab) combined with chemotherapy, according to imaging evaluation, the efficacy of the primary lesion was evaluated as stable disease and the mediastinal lymph nodes were evaluated as partial response. However, the postoperative pathological evaluation showed the primary lesion was pathological complete response and the mediastinal lymph nodes were major pathological response. This indicated that neoadjuvant chemo-immunotherapy was effective for both primary and mediastinal lymph nodes, but regression of the lesions was not synchronous. This study provided a complete process of neoadjuvant treatment, illustrating the effectiveness and safety of neoadjuvant chemo-immunotherapy to a certain extent. It is also suggested that the evaluation of neoadjuvant immunotherapy should be combined with imaging and pathology, and the primary tumor and lymph nodes should be evaluated, respectively.


Limonoid constituents of Euodia rutaecarpa var. bodinieri and their inhibition on NO production in lipopolysaccharide-activated RAW264.7 macrophages.
A new limonoid compound, named evorubodinin (1), was isolated from the dried and nearly ripe fruits of Euodia rutaecarpa (Juss.) Benth. var. bodinieri (Dode) Huang (family Rutaceae), together with two known limonoid compounds, limonin (2) and evolimorutanin (3). The chemical structure of 1 was elucidated by spectroscopic method and single-crystal X-ray diffraction. The inhibitory effects of the isolated compounds 1-3 and the structurally related compounds evodol (4), shihulimonin A1 (5), evodirutaenin (6), 12α-hydroxyrutaevin (7), and rutaevin (8) on nitric oxide (NO) production in lipopolysaccharide-activated RAW264.7 macrophages were also assayed. All compounds 1-8 showed the inhibitory activity, in which both 7 and 8 with the uncommon 5β-H configuration more efficiently inhibited NO production. The results provided valuable information for further investigation of compounds 1-8 as anti-inflammatory agents or lead compounds.


Plastic Deformation through Dislocation Saturation in Ultrasmall Pt Nanocrystals and Its in Situ Atomistic Mechanisms.
The atomic-scale deformation dynamic behaviors of Pt nanocrystals with size of ∼18 nm were in situ investigated using our homemade device in a high-resolution transmission electron microscope. It was discovered that the plastic deformation of the nanosized single crystalline Pt commenced with dislocation "appreciation" first, then followed by a dislocation "saturation" phenomenon. The magnitude of strain plays a key role on dislocation behaviors. At the early to medium stage of deformation, the plastic deformation was controlled by the full dislocation activities accompanied by the formation of Lomer dislocation locks from reaction of full dislocations. When the strain increased to a significant level, stacking faults and extended dislocations as well as Lomer-Cottrell locks appeared. The Lomer-Cottrell locks can unlock through transferring into Lomer dislocation locks first, and then Lomer dislocation locks were destructed under high stresses. The very high density dislocations and the frequent dislocation reactions through Lomer dislocations and Lomer-Cottrell locks may lead to work hardening in nanosized Pt.


[Surgical treatment of portal hypertension in patients with liver cirrhosis].
Surgical options in the treatment of portal hypertension in cirrhotics are reviewed, regarding elective and emergency cases as well as the results in alcoholics and non-alcoholics. After literature review and personal experience analysis, it is concluded that endoscopic sclerotherapy should be the treatment of choice in cirrhotic patients with bleeding esophageal varices. When this fails, distal splenorenal shunt is indicated for compensated Child A and B. Regarding Child C and decompensated Child B, the choice should be a portocaval or meso caval shunts or esophageal transection with a stapler associated to splenectomy.


Hybrid RNA Sequencing Strategy for the Dynamic Transcriptomes of Winter Dormancy in an Evergreen Herbaceous Perennial, Iris japonica.
Japanese iris (Iris japonica) is a popular perennial ornamental that originated in China; it has a long display period and remains green outdoors throughout the year. winter dormancy characteristics contribute greatly to the evergreenness of herbaceous perennials. Thus, it is crucial to explore the mechanism of winter dormancy in this evergreen herbaceous perennial. Here, we used the hybrid RNA-seq strategy including single-molecule real-time (SMRT) and next-generation sequencing (NGS) technologies to generate large-scale Full-length transcripts to examine the shoot apical meristems of Japanese iris. A total of 10.57 Gb clean data for SMRT and over 142 Gb clean data for NGS were generated. Using hybrid error correction, 58,654 full-length transcripts were acquired and comprehensively analysed, and their expression levels were validated by real-time qPCR. This is the first full-length RNA-seq study in the Iris genus; our results provide a valuable resource and improve understanding of RNA processing in this genus, for which little genomic information is available as yet. In addition, our data will facilitate in-depth analyses of winter dormancy mechanisms in herbaceous perennials, especially evergreen monocotyledons.


Membrane enhanced peptide synthesis.
This communication reports a new technology platform that advantageously combines organic solvent nanofiltration (a newly emerging technology capable of molecular separations in organic solvents) with solution phase peptide synthesis-Membrane Enhanced Peptide Synthesis (MEPS).


Proteomics of the Roseobacter clade, a window to the marine microbiology landscape.
Oceans are powered by metabolically-active microorganisms which are main drivers of global biogeochemical cycles on Earth. A decade ago, marine microbiology was boosted with next-generation sequencing capacities and the launch of large metagenomics surveys. High-performing proteomics is now comprehensive enough for reaching genome-wide and systems-wide scales. It is highly complementary to transcriptomics in order to analyze functional dynamics of marine microbes and microbial complex systems. Next-generation proteomics allows new perspectives for better understanding microbial lifestyles and uncovering the complexity of microbial communities. Here, we review the proteomics approaches and outcomes of recent work carried out on one of the most thoroughly studied marine generalist microorganisms, i.e. the Roseobacter clade, as pivotal examples. We also discuss how the study of the proteome of these organisms has helped in the understanding of the ecological strategy and lifestyle of this relevant marine clade, not only in laboratory cultures but also in its natural environment.


A comparison of mice in rebound-thrombocytosis with platelet-hypertransfused mice for the assay of thrombopoietin.
Rebound-thrombocytosis and platelet hypertransfusions were compared as methods of preparing assay animals for the measurement of thrombopoietin (TSF). In immunothrombocythaemic mice, the amount of 35S incorporation into the platelet mass after injections of a standard dose of TSF was related to the length of time after rabbit anti-mouse platelet serum (RAMPS) injection. After 2 platelet transfusions, however, there was no decrease in 35S incorporation values of mice with time after injections of control or TSF-containing substances. When platelet counts were made 3 days after the last platelet transfusion, the counts decreased with the number of transfusions. Mice in rebound-thrombocytosis were responsive to TSF as evidenced by higher platelet counts (P less than 0.05) and increased 35S incorporation into platelets (P less than 0.005), whereas mice made thrombocytotic by platelet transfusions were not. Assuming that increased platelet counts induced by the different techniques affect assay mice only by inhibiting blood cell production by haematopoietic cells, these data are consistent with the hypothesis that sensitivity to TSF depends upon the proliferative state of the megakaryocytic precursor population.


Case report: Acinetobacter baumannii septic arthritis in an immunocompetent infant.
Acinetobacter baumannii is a gram-negative coccobacilli, mainly causing nosocomial infections with poor prognosis, especially in patients with prolonged hospitalization or antibiotics administration. A. baumannii pneumonia is the most common clinical form and usually occurs in critically ill patients in the intensive care unit. However, septic arthritis caused by A. baumannii is rarely reported. In this report, we describe a case of A. baumannii septic arthritis combined with incomplete Kawasaki disease in an infant. The child's chief complaint was a 2-week intermittent fever with poor response to antibiotics. Initial physical examination revealed swollen lymph nodes in the neck, pharynx congestion, and the appearance of rashes. Combined with laboratory tests, the diagnosis of incomplete Kawasaki disease was considered. After administration of high-dose intravenous immunoglobulin and corticosteroids, the child's fever improved and periungual desquamation appeared simultaneously. Swelling of the right knee occurred 5 days after the fever improved and imaging tests of MRI and ultrasound suggested the existence of infection. A diagnosis of septic arthritis was established subsequently, and arthroscopy was carried out. A. baumannii was finally identified by metagenomics next-generation sequencing of joint draining fluid for pathogenic microorganisms. Treatment with meropenem was then started. The patient eventually recovered and was discharged from the hospital after 23 days of treatment with meropenem. Although A. baumannii is not a common bacterium of septic arthritis, this rare infection can still occur in infants. Early diagnosis, pathogenic identification, and target antibiotic treatment are important to reduce the occurrence of joint sequelae.


Pregnancy-associated Steroid Effects on Insulin Sensitivity, Adipogenesis, and Lipogenesis: Role of Wnt/β-Catenin Pathway.
The shift in maternal energy metabolism characteristic of pregnancy is thought to be driven by various hormonal changes, especially of ovarian and placental steroids. Imbalances in circulating estradiol (E2) and progesterone (P4) levels during this period are often associated with metabolic disturbances leading to the development of gestational diabetes mellitus (GDM). Since abnormalities in the Wnt pathway effector transcription factor 7-like 2 (TCF7L2) are commonly associated with the occurrence of GDM, we hypothesized that the canonical or β-catenin-dependent Wnt signaling pathway mediates the metabolic actions of E2 and P4. Our study was aimed at elucidating the metabolic function of the steroids E2 and P4, and examining the role of the canonical Wnt signaling pathway in mediating the actions of these steroids. The ovariectomized (OVX) rat was used as a model system to study the effect of known concentrations of exogenously administered E2 and P4. Niclosamide (Nic) was administered to block Wnt signaling. 3T3-L1 cells were used to analyze changes in differentiation in the presence of the steroids or niclosamide. In the present study, we observed that E2 enhanced insulin sensitivity and inhibited lipogenesis while P4 increased lipogenic gene expression-in 3T3-L1 adipocytes, and in adipose tissue and skeletal muscle of OVX rats when the dosage of E2 and P4 mimicked that of pregnancy. Both E2 and P4 were also found to upregulate Wnt signaling. Nic nhibited the steroid-mediated increase in Wnt signaling in adipocytes and OVX rats. The insulin-sensitizing and antilipogenic actions of E2 were found to be mediated by the canonical Wnt pathway, but the effects of P4 on lipogenesis appeared to be independent of it. Additionally, it was observed that inhibition of Wnt signaling by Nic hastened adipogenic differentiation, and the inhibitory effect of E2 on differentiation was prevented by Nic. The findings presented in this study highlight the role of steroids and Wnt pathway in glucose and lipid metabolism and are relevant to understanding the pathophysiology of metabolic disorders arising from hormonal disturbances.


Single-Base Resolution Map of Evolutionary Constraints and Annotation of Conserved Elements across Major Grass Genomes.
Conserved noncoding sequences (CNSs) are evolutionarily conserved DNA sequences that do not encode proteins but may have potential regulatory roles in gene expression. CNS in crop genomes could be linked to many important agronomic traits and ecological adaptations. Compared with the relatively mature exon annotation protocols, efficient methods are lacking to predict the location of noncoding sequences in the plant genomes. We implemented a computational pipeline that is tailored to the comparisons of plant genomes, yielding a large number of conserved sequences using rice genome as the reference. In this study, we used 17 published grass genomes, along with five monocot genomes as well as the basal angiosperm genome of Amborella trichopoda. Genome alignments among these genomes suggest that at least 12.05% of the rice genome appears to be evolving under constraints in the Poaceae lineage, with close to half of the evolutionarily constrained sequences located outside protein-coding regions. We found evidence for purifying selection acting on the conserved sequences by analyzing segregating SNPs within the rice population. Furthermore, we found that known functional motifs were significantly enriched within CNS, with many motifs associated with the preferred binding of ubiquitous transcription factors. The conserved elements that we have curated are accessible through our public database and the JBrowse server. In-depth functional annotations and evolutionary dynamics of the identified conserved sequences provide a solid foundation for studying gene regulation, genome evolution, as well as to inform gene isolation for cereal biologists.


1995 National Clinical Pharmacy Services Study.
To determine the extent of hospital-based clinical pharmacy services in 1995, we surveyed 1109 United States acute care, general, medical-surgical, and pediatric hospitals with 50 or more licensed beds. Fifteen clinical pharmacy services were assessed to determine pharmacists' specific patient care responsibilities. The percentage of hospitals offering services grew between 1992 and 1995: pharmacokinetic consultations (16% increase), drug therapy protocol management (15%), drug therapy monitoring (8%), drug counseling (13%), and parenteral-enteral nutrition team (6%). All other services increased 0-5%. Pharmacists conducted clinical research in 14% of hospitals, averaging 6.3+/-22.1 protocols/department annually; total budget $96,219+/-$262,026. Patient-focused care predominated in 20% of hospitals, although most pharmacists reported to directors of pharmacy through traditional pharmacy department channels. Clinical pharmacy services continue to expand, with pharmacists providing higher-level direct patient care activities related to drug therapy management and monitoring.


[Pretravel vaccination].
Vaccination is a simple and effective way to protect against certain infectious diseases and is nearly always to be recommended when one is travelling to countries with lesser hygienic standards. This report provides guidance on immunization concerns and describes the individual vaccines most commonly used in travel medicine.