Comparison of activation and blocking procedures in the use of defined antigen substrate spheres (DASS) for quantitative and visual assessment of conjugate activity.
The use of Sepharose beads in the defined antigen substrate sphere (DASS) immunofluorescent system has been restricted by the need for sophisticated equipment for fluorescence quantitation since reliable subjective reading is not possible. This paper describes a method for visual assessment of results in this system. Antigen is coupled to sodium metaperiodate activated. Cross-linked Sepharose 4B beads and blocked with rhodamine-BSA prior to reduction. This procedure eliminates the use of the hazardous cyanogen bromide activation process and is potentially suitable for use in both direct systems for evaluation of specificity and potency of fluorescent conjugates and in indirect systems for serological screening of sera for specific antibody.


Immune complexes in preeclampsia and normal pregnancy.
We determined in normal nonpregnant (group I) and normal pregnant (group II) women and in patients with preeclampsia (group III): (1) immunoglobulins and complement C3b associated with polymorphonuclear leukocytes and platelet surfaces in an attempt to evaluate the interaction in vivo of immune complexes with the membranes of these cells; (2) the occurrence of circulating immune complexes; (3) the serum levels of immunoglobulins, C3, and C4; and (4) the plasma levels of complement C3d. In patients with preeclampsia (group III), the percentages of polymorphonuclear leukocytes and platelets positive for membrane-bound IgG, IgM, IgA, and C3 were significantly higher than the percentages in groups I and II. In group III, there also was a significant increase in circulating immune complexes, as compared to groups I and II. However, circulating immune complexes were also present in significant amounts in normal pregnancy (group II). The plasma levels of complement C3d were markedly increased in the most severe cases of preeclampsia.


Establishment of a lipopolysaccharide-induced inflammation model of human fetal colon cells.
Inflammatory bowel disease (IBD) is a global health problem and there are few cell models for IBD at present. To culture a human fetal colon (FHC) cell line in vitro and establish an FHC cell inflammation model that meets the requirements for high expression of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). FHC cells were cultured with various concentrations of Escherichia coli lipopolysaccharide (LPS) in appropriate media for 0.5, 1, 2, 4, 8, 16 and 24 h to stimulate an inflammatory reaction. The viability of FHC cells was detected by a Cell Counting Kit-8 (CCK-8) assay. The transcriptional levels and protein expression changes of IL-6 and TNF-α in FHC cells were detected by Quantitative Real‑Time Polymerase Chain Reaction (qRT-PCR) and Enzyme‑Linked Immunosorbent Assay (ELISA), respectively. Appropriate stimulation conditions were selected (i.e., LPS concentration and treatment time), based on changes in cell survival rate, and IL-6 and TNF-α expression levels. An LPS concentration higher than 100 µg/mL or a treatment time longer than 24 h resulted in morphological changes and decreased cell survival. By contrast, expression levels of IL-6 and TNF-α significantly increased within 24 h when LPS concentration lower than 100 µg/mL and peaked at 2 h, whilst maintaining cell morphology and viability in FHC cells. The treatment of FHC cells with 100 µg/mL LPS within 24 h was optimal in terms of stimulating IL-6 and TNF-α expression.


One-pot synthesis of metal primary phosphine complexes from O=PCl2R or PCl2R. Isolation and characterization of primary alkylphosphine complexes of a metalloporphyrin.
Treatment of [Ru(II)(Por)(CO)] [Por = porphyrinato(2-)] and O=PCl(2)R [R = Ad (adamantyl), Bu(t), Bu(sec)] or PCl2Mes (Mes = mesityl) with LiAlH4 afforded primary alkyl- and arylphosphine complexes [Ru(II)(Por)(PH2R)2], which have been isolated in pure form and characterized by 1H NMR, 31P NMR, IR, and UV-vis spectroscopy and mass spectrometry. The structures of [Ru(II)(TTP)(PH2Ad)2] and [Ru(II)(F20-TPP)(PH2Mes)2] were determined by X-ray crystallography.


Infrared Multiple Photon Dissociation Spectroscopy Confirms Reversible Water Activation in Mn+(H2O)n, n ≤ 8.
Controlled activation of water molecules is the key to efficient water splitting. Hydrated singly charged manganese ions Mn+(H2O)n exhibit a size-dependent insertion reaction, which is probed by infrared multiple photon dissociation spectroscopy (IRMPD) and FT-ICR mass spectrometry. The noninserted isomer of Mn+(H2O)4 is formed directly in the laser vaporization ion source, while its inserted counterpart HMnOH+(H2O)3 is selectively prepared by gentle removal of water molecules from larger clusters. The IRMPD spectra in the O-H stretch region of both systems are markedly different, and correlate very well with quantum chemical calculations of the respective species at the CCSD(T)/aug-cc-pVDZ//BHandHLYP/aug-cc-pVDZ level of theory. The calculated potential energy surface for water loss from HMnOH+(H2O)3 shows that this cluster ion is metastable. During IRMPD, the system rearranges back to the noninserted Mn+(H2O)3 structure, indicating that the inserted structure requires stabilization by hydration. The studied system serves as an atomically defined single-atom redox-center for reversible metal insertion into the O-H bond, a key step in metal-centered water activation.


Sublethal effects on the hard clam Mercenaria mercenaria after exposure to Aureococcus anophagefferens Chinese strain isolates.
Brown tides caused by Aureococcus anophagefferens occur frequently worldwide and have contributed to the collapse of Mercenaria mercenaria farming in the United States. This economically valuable hard clam has been used in China for more than 20 years. To date, it has remained unknown whether A. anophagefferens Chinese strain has an impact on hard clam cultivation in the coastal areas of China or other sea areas worldwide if it enters through ship ballast water and other ways. In this study, a Chinese strain of A. anophagefferens isolated from the brown tide waters of Bohai Bay, China, was selected to explore its influence on the feedback of hard clams. After being fed with A. anophagefferens, hard clams showed characteristics similar to starvation. The reduced feeding efficiency of hard clams leads to reduced energy intake. However, the immune response and oxidative stress, result in increased energy consumption. An imbalance in the energy budget may be an important reason for hard clam starvation. This study has described the response characteristics of the A. anophagefferens Chinese strain to M. mercenaria, explored the reasons for the negative impact of A. anophagefferens on hard clams, and provides ideas for reducing shellfish aquaculture caused by brown tides.


Closure of a large bronchial fistula with a latissimus dorsi myocutaneous flap.
We describe a case of a large bronchial fistula and empyema after right upper lobectomy that was treated successfully with open window thoracostomy followed by a latissimus dorsi myocutaneous flap and limited thoracoplasty. A latissimus dorsi myocutaneous flap can provide immediate airtight closure of a large bronchial fistula, allowing lavage and curettage of the empyema cavity to reduce the chance of postoperative infection. An important aspect of this technique is that the deepithelialized skin side rather than muscle is sutured to an opening of the bronchus. As compared with other techniques, a latissimus dorsi myocutaneous flap is superior in that it requires a single incision and does not require an intraoperative change of position. In addition, the technique causes little dysfunction of the chest and shoulder and preserves the vascular supply to ensure the viability of the flap even if it was divided in a previous operation.


Brine assemblages of ultrasmall microbial cells within the ice cover of Lake Vida, Antarctica.
The anoxic and freezing brine that permeates Lake Vida's perennial ice below 16 m contains an abundance of very small (≤0.2-μm) particles mixed with a less abundant population of microbial cells ranging from >0.2 to 1.5 μm in length. Fluorescent DNA staining, electron microscopy (EM) observations, elemental analysis, and extraction of high-molecular-weight genomic DNA indicated that a significant portion of these ultrasmall particles are cells. A continuous electron-dense layer surrounding a less electron-dense region was observed by EM, indicating the presence of a biological membrane surrounding a cytoplasm. The ultrasmall cells are 0.192 ± 0.065 μm, with morphology characteristic of coccoid and diplococcic bacterial cells, often surrounded by iron-rich capsular structures. EM observations also detected the presence of smaller unidentified nanoparticles of 0.020 to 0.140 μm among the brine cells. A 16S rRNA gene clone library from the brine 0.1- to 0.2-μm-size fraction revealed a relatively low-diversity assemblage of Bacteria sequences distinct from the previously reported >0.2-μm-cell-size Lake Vida brine assemblage. The brine 0.1- to 0.2-μm-size fraction was dominated by the Proteobacteria-affiliated genera Herbaspirillum, Pseudoalteromonas, and Marinobacter. Cultivation efforts of the 0.1- to 0.2-μm-size fraction led to the isolation of Actinobacteria-affiliated genera Microbacterium and Kocuria. Based on phylogenetic relatedness and microscopic observations, we hypothesize that the ultrasmall cells in Lake Vida brine are ultramicrocells that are likely in a reduced size state as a result of environmental stress or life cycle-related conditions.


Differences in clinical outcomes, health care resource utilization and costs in heart failure patients according to left ventricular ejection fraction.
The impact of left ventricular ejection fraction (LVEF) on health care resource utilization (HCRU) and cost in heart failure (HF) patients is not well known. We aimed to compare outcomes, HCRUs and costs according to LVEF groups. Retrospective, observational study of all patients with an emergency department (ED) visit or admission to a tertiary hospital in Spain 2018 with a primary HF diagnosis. We excluded patients with newly diagnosed heart failure. One-year clinical outcomes, costs and HCRUs were compared according to LVEF (reduced [HFrEF], mildly reduced [HFmrEF], and preserved [HFpEF]). Among 1287 patients with a primary diagnosis of HF in the ED, 365 (28.4%) were discharged to home (ED group), and 919 (71.4%) were hospitalized (hospital group [HG]). In total, 190 patients (14.7%) had HFrEF, 146 (11.4%) HFmrEF, and 951 (73.9%) HFpEF. The mean age was 80.1±10.7 years; 57.1% were female. The median [interquartile range] of costs per patient/y was €1889 [259-6269] in the ED group and €5008 [2747-9589] in the HG (P <.001). Hospitalization rates were higher in patients with HFrEF in the ED group. The median costs of HFrEF per patient/y were higher in patients in both groups: €4763 [2076-17 155] vs €3900 [590-8013] for HFmrEF vs €3812 [259-5486] for HFpEF in the ED group, and €6321 [3335-796] vs €6170 [3189-10484] vs €4636 [2609-8977], respectively, in the hospital group (all P <.001). This difference was driven by the more frequent admission to intensive care units, and greater use of diagnostic and therapeutic tests among HFrEF patients. In HF, LVEF significantly impacts costs and HCRU. Costs were higher in patients with HFrEF, especially those requiring hospitalization, than in those with HFpEF.


The influence of the estrous cycle, persistent estrus, ovariectomy and estrogen replacement, on the numbers and frequency of spontaneously active neurons in slices of the rat preoptic region in vitro.
Spontaneous single-unit activity was studied in the preoptic region of rat brain slices. Similar unit frequencies were recorded during the estrous cycle and for all ovariectomized (OVX) rats (median frequencies between 0.8 and 2.0 Hz). Higher frequencies were recorded in persistent estrus (PE) (median 3.5 Hz) and in males (median 3.4 Hz), P vs estrus less than 0.001. The mean percentage of tracks with units was low at estrus (15%), at diestrus (18%), in OVX rats (16%) and male rats (22%), and was significantly increased in metestrus (36%) and proestrus (33%) (P vs estrus less than 0.01) and in OVX rats after estrogen treatment (P less than 0.05 to P less than 0.01). It is suggested that the increased number of units found in OVX rats after estrogen treatment and in PE rats are both effects of prolonged elevated levels of estrogen in the brain.


Spontaneous hemothorax in a patient with neurofibromatosis type 1 and undiagnosed pheochromocytoma.
Spontaneous hemothorax in neurofibromatosis type 1 rarely occurs, is potentially life-threatening, and requires expedient management. We present a case of massive hemothorax in a patient with neurofibromatosis type 1 caused by spontaneous rupture of the right internal mammary artery. A subsequently diagnosed underlying pheochromocytoma may be implicated in rupture of the arterial wall.


Determination of glycyrrhetic acid in human plasma by HPLC-MS method and investigation of its pharmacokinetics.
To develop a high performance liquid chromatography mass spectrometry (HPLC-MS) method for the determination of the glycyrrhetic acid (GA) in human plasma and for the investigation of its pharmacokinetics after the oral administration of 150 mg diammonium glycyrrhizinate test and reference capsule formulations. The GA in plasma was extracted with ethyl acetate, separated on a C(18) column with a mobile phase of methanol (5 mmol/L ammonium acetate)-water (85 : 15, V/V) and analysed using a MS detector. Ursolic acid (UA) was used as internal standard. The target ions were m/z 469.5 for GA and m/z 455.6 for UA, the fragment voltages were 200 V and 100 V for GA and UA respectively. The calibration curve was linear over the range of 0.5-200 ng/mL (r = 0.9974). The limit of quantification for GA in plasma was 0.5 ng/mL, the recovery was 76.0-80.0%, and the inter- and intra-day relative standard deviations (RSD) were <12%. The pharmacokinetic parameters of GA after a single dose of 150 mg diammonium glycyrrhizinate test and reference were as follows: the half life (t(1/2)) 9.65 +/- 3.54 h and 9.46 +/- 2.85 h, the time to peak concentration (T(max)) 10.95 +/- 1.32 h and 11.00 +/- 1.30 h, the peak concentration (C(max)) 95.57 +/- 43.06 ng/mL and 103.89 +/- 49.24 ng/mL; the area under time-concentration curve (AUC(0-48) and AUC(0-infinity)) 1281.84 +/- 527.11 ng.h/mL and 1367.74 +/- 563.27 ng.h/mL, 1314.32 +/- 566.40 ng.h/mL and 1396.97 +/- 630.06 ng.h/mL. The relative bioavailability of diammonium glycyrrhizinate capsule was 98.88 +/- 12.98%. The assay was sensitive, accurate and convenient, and can be used for the determination of GA in human plasma. Comparison of the bioavailability and pharmacokinetic profile of GA indicated that the test and reference capsules were bioequivalent.


Delayed-type hypersensitivity to human gonadotropin: case report.
To investigate adverse reactions to hMG preparations in two women in IVF programs. Two case reports with skin tests for delayed hypersensitivity (DH) to hMG and a biopsy of one delayed reaction. Allergy and infertility clinics in university medical center. Two affected patents with a history of local reactions to the injected hMG, one of whom also had fever, and nine control subjects. Skin tests and biopsy. Delayed hypersensitivity skin response to hMG in affected patients indicated by timing and biopsy results. Negative skin test with the purified hFSH, which was also used in treatment with no adverse effects. Use of the purified preparation avoids DH reaction.


Neuronal SNAP-23 is critical for synaptic plasticity and spatial memory independently of NMDA receptor regulation.
SNARE-mediated membrane fusion plays a crucial role in presynaptic vesicle exocytosis and also in postsynaptic receptor delivery. The latter is considered particularly important for synaptic plasticity and learning and memory, yet the identity of the key SNARE proteins remains elusive. Here, we investigate the role of neuronal synaptosomal-associated protein-23 (SNAP-23) by analyzing pyramidal-neuron specific SNAP-23 conditional knockout (cKO) mice. Electrophysiological analysis of SNAP-23 deficient neurons using acute hippocampal slices showed normal basal neurotransmission in CA3-CA1 synapses with unchanged AMPA and NMDA currents. Nevertheless, we found theta-burst stimulation-induced long-term potentiation (LTP) was vastly diminished in SNAP-23 cKO slices. Moreover, unlike syntaxin-4 cKO mice where both basal neurotransmission and LTP decrease manifested changes in a broad set of behavioral tasks, deficits of SNAP-23 cKO are more limited to spatial memory. Our data reveal that neuronal SNAP-23 is selectively crucial for synaptic plasticity and spatial memory without affecting basal glutamate receptor function.


Increased resting intracellular calcium modulates NF-κB-dependent inducible nitric-oxide synthase gene expression in dystrophic mdx skeletal myotubes.
Duchenne muscular dystrophy (DMD) is a genetic disorder caused by dystrophin mutations, characterized by chronic inflammation and severe muscle wasting. Dystrophic muscles exhibit activated immune cell infiltrates, up-regulated inflammatory gene expression, and increased NF-κB activity, but the contribution of the skeletal muscle cell to this process has been unclear. The aim of this work was to study the pathways that contribute to the increased resting calcium ([Ca(2+)](rest)) observed in mdx myotubes and its possible link with up-regulation of NF-κB and pro-inflammatory gene expression in dystrophic muscle cells. [Ca(2+)](rest) was higher in mdx than in WT myotubes (308 ± 6 versus 113 ± 2 nm, p < 0.001). In mdx myotubes, both the inhibition of Ca(2+) entry (low Ca(2+) solution, Ca(2+)-free solution, and Gd(3+)) and blockade of either ryanodine receptors or inositol 1,4,5-trisphosphate receptors reduced [Ca(2+)](rest). Basal activity of NF-κB was significantly up-regulated in mdx versus WT myotubes. There was an increased transcriptional activity and p65 nuclear localization, which could be reversed when [Ca(2+)](rest) was reduced. Levels of mRNA for TNFα, IL-1β, and IL-6 were similar in WT and mdx myotubes, whereas inducible nitric-oxide synthase (iNOS) expression was increased 5-fold. Reducing [Ca(2+)](rest) using different strategies reduced iNOS gene expression presumably as a result of decreased activation of NF-κB. We propose that NF-κB, modulated by increased [Ca(2+)](rest), is constitutively active in mdx myotubes, and this mechanism can account for iNOS overexpression and the increase in reactive nitrogen species that promote damage in dystrophic skeletal muscle cells.


Human platelets effectively kill K-562 cells, a chronic myelogenic leukemia cell line, in vitro.
The cytotoxic effect of isolated human platelets on leukemic cells has been examined in order to investigate the role of platelets in host defense systems. K-562 cells (a chronic myelogenic leukemia cell line) showed significant change in their morphology and were killed when they were incubated with platelets in serum-free medium for several hours at 37 degrees C, a condition where no killing of normal peripheral lymphocytes occurred. Some protease inhibitors inhibited the cytotoxicity of platelets against K-562 cells. Our results suggest that platelets may be involved in host defense against neoplasia and that certain proteases are implicated in the cytotoxic effect of platelets.


Significant Liver-Related Morbidity After Bariatric Surgery and Its Reversal-a Case Series.
Nonalcoholic fatty liver disease (NAFLD) occurs in up to 80% of patients with obesity. Current data suggest an improvement of NAFLD after established bariatric procedures. This study investigated liver function impairment after Roux-en-Y gastric bypass (RYGB) and one-anastomosis gastric bypass (OAGB). University Hospital, Bariatric Surgery Unit METHODS: In this single-center case series, consecutive in- and outpatients after bariatric surgery who presented with severe liver dysfunction from March 2014 to February 2017 were included and followed until March 2017. In total, 10 patients (m:f = 2:8; median age 48 years, range 22-66 years) were included. Liver dysfunction occurred after a median postoperative time of 15 months (range 2-88 months). Median %excess weight loss at that time was 110.6% (range 85.2-155.5%). Liver steatosis/fibrosis occurred in 70%, cirrhosis in 30% of patients, and led to fatigue (90%), ascites (70%), hepatic encephalopathy (30%), and upper gastrointestinal bleeding (20%). Elevation of transaminases, impairment of coagulation parameters, thrombocytopenia, and hypoalbuminemia were present in 70, 80, 70, and 100%, respectively. In eight patients, lengthening of the alimentary/common limb led to an improvement or complete remission of symptoms. In one patient, liver transplantation was required, one patient deceased due to septic shock and decompensated liver disease. Severe liver dysfunction may also occur after bariatric procedures such as OAGB and RYGB. A comprehensive, meticulous follow-up for early identification of postoperative liver impairment should be aspired. Bypass length reduction led to a fast improvement in all patients.


Validity and reliability of the Turkish version of the paternal breastfeeding self-efficacy scale - Short form for fathers.
Women supported by their partners are more likely to initiate and maintain breastfeeding and overcome related challenges. Therefore, reliable measurement tools are needed to determine whether fathers can provide this support. This study aimed to (1) examine the psychometric properties of the Paternal Breastfeeding Self-Efficacy Scale-Short Form (BSES-SF) in Turkish fathers, including internal consistency reliability, test-retest reliability, construct validity using Confirmatory Factor Analysis (CFA); and (2) assess the relationship between the BSES-SF and paternal demographic factors. A methodologically study was conducted between December 26-2018 and June 26-2019 at the pediatrics clinics of two research hospitals of medical schools in Konya, Turkey. The sample consisted of 221 fathers of infants aged 2 to 6 weeks who visited the clinics for routine examinations. Data were collected using a sociodemographic questionnaire and the Turkish version of the Paternal BSES-SF. After evaluating the language equivalence and content validity of the scale, test-retest reliability, internal consistency and construct validity were examined. In evaluation of the data frequency/percentage, mean, standard deviation, independent groups t test, ANOVA Analysis, Bartlett's Test of Sphericity, Confirmatory Factor Analysis, Pearson Product-Moment correlation and Cronbach α analysis were used. The study was approved by Interventional Clinical Research Ethics Committee of the Faculty of Health Sciences of Selcuk University in Turkey. The translated Paternal BSES-SF had a Cronbach's alpha of 0.93 and a test-retest reliability coefficient of 0.96. The factor loadings ranged from 0.42 to 0.76. The Paternal BSES-SF had a one-factor structure similar to the original scale. Fathers who were unemployed, had lower economic status, and unplanned pregnancy had significantly lower mean Paternal BSES-SF scores. Paternal education regarding breastfeeding increased mean Paternal BSES-SF retest scores (p<0.05). The Paternal BSES-SF was a valid and reliable measure to assess fathers' confidence in their ability to assist mothers with breastfeeding in Turkey. Turkish researchers and health workers can use this instrument as a reference for promoting exclusive breastfeeding.


Liquid chromatography-electrospray ionisation mass spectrometry for the determination of nine selected benzodiazepines in human plasma and oral fluid.
A new simple and rapid liquid chromatographic-mass spectrometric technique was designed for the determination of nine benzodiazepines in plasma and oral fluid. Benzodiazepines were extracted from alkalinised spiked and clinical plasma and oral fluid samples using a single step, liquid-liquid extraction procedure with diethyl ether. The chromatographic separation was performed with a Xterra RP18, 5 microm (150 x 2.1 mm i.d.) reversed-phase column using deuterated analogues of the analytes as internal standard. The recovery ranged from 70.3 to 86.9% for plasma and 63.9 to 77.2% for oral fluid. The limits of detection ranged from 0.5 to 1 ng/ml in plasma and 0.1 to 0.2 ng/ml for oral fluid. The method was validated for all the compounds, including linearity and the main precision parameters. The procedure, showed to be sensitive and specific, was applied to real plasma and oral fluid samples. The method is especially useful to analyse saliva samples from drivers undergoing roadside drug controls.


Transdifferentiation of outgrowth cells and cultured epithelial cells from swine trachea.
The morphologic and functional properties of explant out-growth cells and epithelial cells isolated from swine trachea epithelium by proteolysis were examined. A mixed population of ciliated, serous, and basal cells, obtained from out-growths, from proteolysis of trachea epithelium, and from unattached explants in organ culture, all yielded cell cultures that werecomposed almost entirely of mucus-secreting cells. When the cells were grown in primary or secondary culture on a modified collagen matrix in supplemented HAM:DMEM (1:1) medium they expressed a mucus-secreting phenotype with numerous mucus granules at various stages of maturation and incorporated [3H]GlcN and 35SO4 into secreied mucin glycoproteins. Results obtained in these studies suggest that extensive transdifferentiation of ciliated and serous cells to mucus-secreting-cells occurs after the release and during subsequent attachment and culture. Ciliated cells containing mucus granules were seen in various stages of cilia resorption. Basal cells containing mucus granules were also frequently observed. The number of mucus-secreting cells and the synthesis of mucin glycoproteins increased dramatically with time of attachment and culture, whereas cell proliferation, population doubling time of 72 h, and incorporation of [3H]-thymidine into DNA increased much more slowly. The number of mucus-secreting cells correlated closely with the level of secretion of mucin glycoproteins. Taken collectively, these studies help to elucidate the transdifferentiation process, which dramatically increases the number of mucus-secreting cells after disruption and release of epithelial cells from swine tracheobronchial epithelium. A similar mechanism involving disruption of the extracellular matrix may be involved in the stimulation of hypersecretion of mucus and mucin glycoproteins by chemical and infections irritants.


Magnetic separation of iron oxide nanoparticles to improve their application for magnetic particle imaging.
Magnetic particle imaging (MPI) is a promising medical imaging technique for visualizing the three-dimensional distribution of tracer materials, specifically iron oxide nanoparticles (IONP). The optimization of magnetic nanoparticles (MNP) plays an essential role to improve the image resolution and sensitivity of imaging techniques. In this work, the optimization of commercial IONP (EMG 700, Ferrotec) coated with anionic surfactants was carried out using magnetic separation (MS) technique, by a low gradient magnetic separation (LGMS) (<15 T m-1) method, to improve their performance as MPI tracers. The magnetophoretical behavior of the samples in different concentrations ranging from 2 to 120 mmol l-1 was investigated over 24 h of separation. The samples were characterized by dynamic light scattering (DLS), AC susceptibility (ACS), magnetic particle spectroscopy (MPS) and they were imaged in a preclinical MPI scanner, before and after MS. DLS results showed that by increasing the concentration from 2 to 120 mmol l-1 the hydrodynamic diameter of MNP decrease from 75 to 47 nm and size distribution decrease from 0.19 to 0.11 after 4 min MS. In addition, the MPS results demonstrated the third harmonic amplitude normalized to the iron amount [Formula: see text] and harmonic ratio [Formula: see text] of signal increase from 8.38 to 10.59 Am2 kg-1 (Fe) and 24.21-26.60, respectively. Furthermore, the MPI images of the samples after separation showed higher MPI resolution. Therefore, LGMS can be considered as a valuable method to narrow and control the size distribution of MNP for MPI.


Effects of insulin-like growth factor (IGF) binding protein-3 (IGFBP-3) on endometrial cancer (HHUA) cell apoptosis and EGF stimulated cell proliferation in vitro.
IGFBP-3 has been demonstrated to stimulate or inhibit cell proliferation independently of its ability to bind IGF and a specific IGFBP-3 receptor has been proposed. EGF has been implicated in the cancer development and carcinogenesis. Only limited data are available on the crosstalk between IGFBP-3 signaling and EGF induced cell survival and signal transduction. The current studies were undertaken to characterize IGFBP-3 binding to endometrial cancer cells (HHUA) and determine its biological effects, as well as whether IGFBP-3 exposure alters the cell proliferation stimulated by EGF. Cell proliferation and apoptosis were analyzed by ELISA using specific antibodies. The interaction between HHUA cell and IGFBP-3 was analyzed using a biosensor. The phosphorylation abundance of specific proteins and their phosphorylation in response to EGF and IGFBP-3 was analyzed by immunoprecipitation followed by immunoblotting. Biosensor analysis showed that IGFBP-3 could bind to HHUA cell surface. IGFBP-3 inhibited BrdU uptake, potentiated ssDNA production and induced p53 in HHUA cells. Although EGF stimulated HHUA cell proliferation and Akt phosphorylation, IGFBP-3 inhibited cell proliferation and Akt phosphorylation that had been stimulated by EGF. However, EGF receptor phosphorylation and expression were not reduced by IGFBP-3. Since HHUA cells lack IGF receptors and do not show biological response to IGF these results suggest that IGFBP-3 can bind to HHUA cells, inhibit cell proliferation and induce apoptosis independently of its ability to bind to IGFs possibly by binding to an IGFBP-3 receptor. Taken together these findings demonstrate that IGFBP-3 binds to HHUA cell surface, and inhibits cell division induced by EGF, possibly by modulating the EGF-mediated signal transduction system.


An improved spider optimization algorithm coordinated by pheromones.
Swarm intelligence algorithm is an important evolutionary computation method that optimizes the objective function by imitating the behaviors of various organisms in nature. A two-stage swarm intelligence algorithm named spider pheromone coordination algorithm (SPC) is proposed in this paper. SPC tries to explore as many feasible solutions as possible on the cobweb at the positioning stage. It simulates the release and reception of different pheromones between spiders at the hunting stage, and then spiders move towards prey under the co-action of winds and pheromones. Different from the existing algorithms, SPC simulates the process that spiders accomplish intra-species communications through different pheromones and considers the impact on spider wind movement. A large number of typical benchmark functions are used in comparative numerical experiments to verify the performances of SPC. Experiments are made to compare SPC with a series of swarm intelligence algorithms, showing that SPC has higher convergence accuracy and stronger global searchability, effectively keeping the diversity of feasible solutions.


Demonstration of high-affinity binding sites for C3a anaphylatoxin on guinea-pig platelets.
3H-serotonin release from guinea-pig platelets was demonstrated to be the consequence of C3a binding to these cells. A Scatchard analysis of dose-response data of the 125I-C3a binding pattern to guinea-pig platelets pointed to the existence of binding sites with high and low affinity for the C3a molecule (HA and LA receptors). HA receptors are specific for C3a with intact C-terminal arginine. whereas C3adesarg only interacts with LA receptors. The release of serotonin may be induced by a combined reaction of C3a with HA receptors and LA receptors on the platelet membrane.


Brachial plexus injury caused by electric current through the ulnar nerve. Case report and review of the literature.
A case of brachial plexus injury caused by electric current is reported. A 14-year-old boy touched a bare electric cord with his right fifth finger. The electric current ran from the finger through the extremity to the neck. Then it caused brachial plexus palsy gradually. The clinical course and the electrophysiological examination revealed that the affected nerve fibers were in a state of neurapraxia.


Patterns of lactate values after congenital heart surgery and timing of cardiopulmonary support.
We sought to determine if postoperative serial lactate determinations follow predictable patterns that could be useful in directing management, especially the initiation of postoperative mechanical cardiopulmonary support (CPS). Eight patients undergoing CPS in a 2-year period and 147 patients not requiring postoperative CPS in 6 months of that period were stratified into 6 categories based on short-term risk for mortality (1 being the lowest risk). Lactate values for the first 48 hours postoperatively were retrospectively analyzed. Survivors not requiring CPS in category 6 (n = 16) followed a distinct pattern different from those of categories 1 through 4 (n = 128). Review of postoperative CPS survivors (n = 4) indicated that CPS was initiated electively without cardiac arrest in all 4, and lactate values showed a downward trend within 12 hours of initiation in all cases (mean lactate, 10.12 +/- 1.88 mmol/L; range, 1.4 to 16 mmol/L; mean initiation time, 16.5 hours postoperatively). Three fourths of the CPS nonsurvivors suffered cardiac arrest before CPS and showed rising lactate values despite support (mean lactate, 11.95 +/- 1.37 mmol/L; range, 1.6 to 18.6 mmol/L; mean initiation time, 21.25 hours postoperatively). Indications for initiation of CPS in patients with elevated lactate values were reviewed. Two thirds of patients who died without CPS had preterminal cardiac arrest. We have defined the normal pattern of postoperative lactate values in our institution. These data suggest that an abnormal lactate pattern may be useful in determining the timing of CPS initiation in hemodynamically stable patients with high or rising lactate values, before cardiac arrest or end organ damage.


Fatal spirochetosis due to a relapsing fever-like Borrelia sp. in a northern spotted owl.
Acute septicemic spirochetosis was diagnosed in an adult male northern spotted owl (Strix occidentalis caurina) found dead in Kittitas County, Washington, USA. Gross necropsy findings included marked enlargement of the liver and spleen and serofibrinous deposits on the serous membranes lining the body cavities and the pericardial and perihepatic sacs. Microscopic observations included macrophage infiltration in the liver and spleen with mild thrombosis and multifocal necrosis, as well as hemorrhage and acute inflammation in the choroid plexus of the brain. No viruses or pathogenic bacteria were isolated from brain, liver, or spleen, and no parasites were found in blood smears or impression smears of the liver. Chlamydial culture attempts were unsuccessful and no chlamydial antibodies were detected in serum. In silver-stained microscopic sections and by transmission electron microscopy of liver, numerous long, thin, spiral-shaped bacteria were seen in the liver, spleen, cerebral ventricles, and within blood vessels in many organs. The organism was identified as a member of the Borrelia genus by sequence analysis of the PCR-amplified 16S rRNA gene. The most closely related species is B. hermsii, an agent of relapsing fever in humans in the western United States. This is the first report of a relapsing fever-related Borrelia in a wild bird.


Fractionation of Bothrops pirajai snake venom: isolation and characterization of piratoxin-I, a new myotoxic protein.
Whole desiccated venom of Bothrops pirajai was fractionated on a gel filtration (Sephadex G-75) column. Phospholipase A2, arginine esterase and clotting activity profiles of the six fractions (SI to SVI) obtained were determined. Fraction SIV from the gel filtration column was subjected to chromatography on SP-Sephadex C-25. It was resolved into five subfractions (SIV-SP1, to SIV-SP5). Fractions SIV-SP1, SIV-SP2 and SIV-SP3 showed phospholipase A2 activity but, among these fractions, only SIV-SP3 was homogeneous. Induction of myonecrosis by SIV-SP3, SIV-SP4 and SIV-SP5 was demonstrated by their ability to release serum creatine kinase, and for SIV-SP5, to induce histological alterations in the injected mouse muscle. Chemical characterization by determination of mol. wts, isoelectric focusing and direct manual sequencing of the N-terminal region was performed for SIV-SP3, SIV-SP4 and SIV-SP5. When compared with bothropstoxin-I, the myotoxin SIV-SP5 showed the same total number of amino acid residues (121) and constant molar ratio for all but three amino acids. We have named this toxin piratoxin-I (PrTX-I).


Adipose tissue attracts and protects acute lymphoblastic leukemia cells from chemotherapy.
Obesity is associated with an increased risk of acute lymphoblastic leukemia (ALL) relapse. Using mouse and cell co-culture models, we investigated whether adipose tissue attracts ALL to a protective microenvironment. Syngeneically implanted ALL cells migrated into adipose tissue within ten days. In vitro, murine ALL cells migrated towards adipose tissue explants and 3T3-L1 adipocytes. Human and mouse ALL cells migrated toward adipocyte conditioned media, which was mediated by SDF-1α. In addition, adipose tissue explants protected ALL cells against daunorubicin and vincristine. Our findings suggest that ALL migration into adipose tissue could contribute to drug resistance and potentially relapse.


Population genomics of louping ill virus provide new insights into the evolution of tick-borne flaviviruses.
The emergence and spread of tick-borne arboviruses pose an increased challenge to human and animal health. In Europe this is demonstrated by the increasingly wide distribution of tick-borne encephalitis virus (TBEV, Flavivirus, Flaviviridae), which has recently been found in the United Kingdom (UK). However, much less is known about other tick-borne flaviviruses (TBFV), such as the closely related louping ill virus (LIV), an animal pathogen which is endemic to the UK and Ireland, but which has been detected in other parts of Europe including Scandinavia and Russia. The emergence and potential spatial overlap of these viruses necessitates improved understanding of LIV genomic diversity, geographic spread and evolutionary history. We sequenced a virus archive composed of 22 LIV isolates which had been sampled throughout the UK over a period of over 80 years. Combining this dataset with published virus sequences, we detected no sign of recombination and found low diversity and limited evidence for positive selection in the LIV genome. Phylogenetic analysis provided evidence of geographic clustering as well as long-distance movement, including movement events that appear recent. However, despite genomic data and an 80-year time span, we found that the data contained insufficient temporal signal to reliably estimate a molecular clock rate for LIV. Additional analyses revealed that this also applied to TBEV, albeit to a lesser extent, pointing to a general problem with phylogenetic dating for TBFV. The 22 LIV genomes generated during this study provide a more reliable LIV phylogeny, improving our knowledge of the evolution of tick-borne flaviviruses. Our inability to estimate a molecular clock rate for both LIV and TBEV suggests that temporal calibration of tick-borne flavivirus evolution should be interpreted with caution and highlight a unique aspect of these viruses which may be explained by their reliance on tick vectors.


Spatial -omics technologies: the new enterprise in 3D breast cancer models.
The fields of tissue bioengineering, -omics, and spatial biology are advancing rapidly, each offering the opportunity for a paradigm shift in breast cancer research. However, to date, collaboration between these fields has not reached its full potential. In this review, we describe the most recently generated 3D breast cancer models regarding the biomaterials and technological platforms employed. Additionally, their biological evaluation is reported, highlighting their advantages and limitations. Specifically, we focus on the most up-to-date -omics and spatial biology techniques, which can generate a deeper understanding of the biological relevance of bioengineered 3D breast cancer in vitro models, thus paving the way towards truly clinically relevant microphysiological systems, improved drug development success rates, and personalised medicine approaches.


Three-dimensional ultrasound integrating nomogram and the blood flow image for prostate cancer diagnosis and biopsy: A retrospective study.
Prostate cancer (PCa) is the second most common male cancer in the world and based on its high prevalence and overwhelming effect on patients, more precise diagnostic and therapeutic methods are essential research topics. As such, this study aims to evaluate the value of three-dimensional transrectal ultrasound (3D-TRUS) in the detection, diagnosis and biopsy of PCa, and to provide a basis for clinical practice of PCa. Retrospective analysis and comparison of a total of 401 male patients who underwent prostate TRUS in our hospital from 2019 to 2020 were conducted, with all patients having prostate biopsy. Nomogram was used to estimate the probability of different ultrasound signs in diagnosing prostate cancer. The ROC curve was used to estimate the screening and diagnosis rates of 3D-TRUS, MRI and TRUS for prostate cancer. A total of 401 patients were randomly divided into two groups according to different methods of prostate ultrasonography, namely the TRUS group (251 patients) and the 3D-TRUS group (150 patients). Of these cases, 111 patients in 3D-TRUS group underwent MRI scan. The nomogram further determined the value of 3D-TRUS for prostate cancer. The ROC AUC of prostate cancer detected by TRUS, MRI and 3D-TRUS was 0.5580, 0.6216 and 0.6267 respectively. Biopsy complications were lower in 3D-TRUS group than TRUS group, which was statistically significant (P<0.005). The accuracy of 3D-TRUS was higher in diagnosis and biopsy of prostate cancer. Meanwhile, the positive rate of biopsy could be improved under direct visualization of 3D-TRUS, and the complications could be decreased markedly. Therefore, 3D-TRUS was of high clinical value in diagnosis and biopsy of prostate cancer.


Dynamic behavior of CO2 uptake as affected by light: system identification based on spectral analysis.
The dynamic behavior of CO2 uptake in sunflower plants was measured in a computer controlled apparatus and identified systematically using spectral analysis.To obtain impulse responses of net CO2 uptake, power spectra were estimated by the Fast Fourier Transform (FFT) method. FFT was done by computing 512 separate data points sampled at one minute intervals. From examination of coherency, it was determined that dynamic behavior of CO2 uptake could be estimated by linear filtering based on impulse response as affected by the light in changes slower than 0.08 cycle min-1. This suggests that other dynamic phenomena in physiological ecology could be estimated effectively by using advanced system theory involving many algorithms.


Studies on H-Y antigen in different cell fractions of the testis during pubescence: immature germ cells are H-Y antigen negative.
Various cell types of the rat testis during pubescence, including germ, Sertoli, and Leydig cells, were partially enriched. The fractions were tested for the presence, binding, and secretion of H-Y antigen. The main results are: Immature germ cells are H-Y antigen-negative until the late diploid stages, and late primary spermatocytes or spermatids become positive; the somatic cells of the gonad are positive at all ages examined (18 days old to adulthood). Secretion of H-Y antigen is restricted to the Sertoli cell fraction. Binding of externally supplied antigen takes place on Leydig cells; the Sertoli cell surface will be saturated because of active secretion; there is no binding to germ cells. Thus, immature germ cells seem to be the only H-Y antigen-negative cells of the male organism, and the Sertoli cells seem to be the only ones to secrete H-Y antigen.


5-HT and carbohydrate suppression: effects of 5-HT antagonists on the action of d-fenfluramine and DOI.
The effects of several 5-hydroxytryptamine (5-HT) receptor antagonists on the anorectic effect of d-fenfluramine and the 5-HT2/5-HT1C agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) were examined in a dietary paradigm that appears to be sensitive to 5-HT-induced carbohydrate suppression. In this paradigm, deprived rats are provided with a nutritionally complete hydrated chow mash diet together with an optional carbohydrate supplement of powdered Polycose. Both d-fenfluramine and DOI produced a clear suppression of total energy intake and carbohydrate (Polycose) intake. However, the mechanisms underlying these effects are different. The effect of d-fenfluramine in this paradigm was attenuated by the 5-HT1/5-HT2 receptor antagonist metergoline and partially attenuated by the 5-HT1A/5-HT1B receptor antagonist (+/-)cyanopindolol. In contrast, d-fenfluramine's effect was not antagonised by the 5-HT2 receptor antagonist ketanserin, the 5-HT3 receptor antagonist (3 alpha-tropanyl)-1H-indole-3-carboxylic acid ester (ICS-205,930), the 5-HT2/5-HT1C receptor antagonist ritanserin, or the peripheral 5-HT receptor antagonist xylamidine. However, the effect of DOI in this paradigm was significantly attenuated by ketanserin but was not antagonised by either ritanserin or (+/-)cyanopindolol. Therefore, the suppressive effect of these two 5-HT drugs on total and Polycose intake appears to be mediated, respectively, by 5-HT1B/5-HT1C receptors (d-fenfluramine) and 5-HT2 receptors (DOI).


Transhiatal jejunal interposition preserving the whole stomach and vagal trunk for a benign esophageal stricture in a male adolescent: report of a case.
Benign esophageal strictures are generally treated with medication and balloon dilation; however, when repeated dilations fail, surgery is the only option. When performing surgery for benign esophageal stricture in young patients, it is important to consider not only the surgical stress and likelihood of complications but also digestive function after reconstruction, the durability of the reconstruction, and the potential for cancerous change in the reconstructed organs. We describe how we treated a 14-year-old boy with benign esophageal stricture by performing transhiatal esophagectomy assisted by mediastinoscopy, preserving the whole stomach and vagus nerve, and interposing pedicled jejunum between the cervical esophagus and stomach through a posterior mediastinal route, with good long-term results.


Mycobacterium Avium in Miniature Schnauzer From Argentina: A Series of Cases.
Environmental mycobacteria such as those from the Mycobacterium avium-intacellulare complex may cause disseminated and severe disease in dogs with genetic predisposition. A series of cases of 4 miniature schnauzers with nonspecific clinical signs and the diagnostic tests are described. Complementary means of diagnosis including complete blood count, biochemical serum analyses and fine needle aspiration cytology staining were performed. The bacteriological culture followed by PCR amplification of 1245 and 901 insertion sequences, allowed the identification of Mycobacterium avium subsp. hominissuis. This environmental Mycobacteria normally do not cause severe disease in dogs or other species, but when CARD-9 gene presents mutations, dogs may become extremely susceptible and disease is fast, disseminated, and fatal. Antibiotic therapy can be applied under veterinary consideration in specific situations, as treatment is usually applied for a long period of time. Although zoonotic risk is low as the Mycobacterium is environmental, contamination of the location may be high, and immunosuppressed animals and humans can develop infection as well. This report may aid clinical veterinarians in the diagnosis, treatment, and prognosis in similar cases of this breed and others with the genetic predisposition.


Redefining (somatoform) pain disorder in ICD-10: a compromise of different interest groups in Germany.
Pain is one of the most frequent reasons to visit health professionals. Many patients suffering from chronic pain conditions not only need medical treatment but also psychiatric or psychological interventions. This additional treatment need should be underlined using an ICD section F diagnosis. The current ICD-10 diagnosis of somatoform pain disorder requests psychological causation of the pain, which is frequently unclear or difficult to decide. In Germany, the different interest groups, namely of psychiatry, pain research, psychosomatic medicine and clinical psychology, met to find a consensus on how to re-classify pain disorder under section F of ICD-10. This manuscript summarizes the result. A diagnosis of pain disorder is necessary to underline the additional need of psychiatric/psychological interventions in chronic pain conditions. This diagnosis should include psychological features that are relevant for development or maintenance of chronic pain. In contrast to earlier attempts of redefining pain diagnoses, our attempt included representatives of the association for the study of pain.


Internalization, axonal transport and release of fibrillar forms of alpha-synuclein.
Intra-neuronal protein aggregates made of fibrillar alpha-synuclein (α-syn) are the hallmark of Parkinson's disease (PD). With time, these aggregates spread through the brain following axonal projections. Understanding the mechanism of this spread is central to the study of the progressive nature of PD. Here we review data relevant to the uptake, transport and release of α-syn fibrils. We summarize several cell surface receptors that regulate the uptake of α-syn fibrils by neurons. The aggregates are then transported along axons, both in the anterograde and retrograde direction. The kinetics of transport suggests that they are part of the slow component b of axonal transport. Recent findings indicate that aggregated α-syn is secreted by neurons by non-canonical pathways that may implicate various molecular chaperones including USP19 and the DnaJ/Hsc70 complex. Additionally, α-syn fibrils may also be released and transmitted from neuron-to-neuron via exosomes and tunneling nanotubes. Understanding these different mechanisms and molecular players underlying α-syn spread is crucial for the development of therapies that could halt the progression of α-syn-related degenerative diseases.


Temperature regulates fatty acid desaturases at a transcriptional level and modulates the fatty acid profile in the Antarctic microalga Chlamydomonas sp. ICE-L.
Chlamydomonas sp. ICE-L which can thrive in extreme environments of the Antarctic is a major biomass producer. The FAD genes in Chlamydomonas sp. ICE-L were obtained and sequence alignment showed that these genes are homologous to known FADs with conserved histidine motifs. In this study, we analyzed the transcription of five FADs and FA compositions at different temperatures. The results showed that the expressions of Δ9CiFAD, ω3CiFAD1 and ω3CiFAD2 were apparently up-regulated at 0°C, however, the up-regulation of Δ6CiFAD intensified with rising temperature. Meanwhile, analysis of the FA compositions showed that PUFAs were dominant compositions, accounting for more than 75% TFA in Chlamydomonas sp. ICE-L. Furthermore, PUFAs were significantly increased at 0 and 5°C, which may be attributed to higher proportions of C18:3 and C20:3. Moreover, PUFAs were significantly decreased at 15°C whereas SFAs were significantly increased.


Sjögren's syndrome concurrent with protein-losing gastroenteropathy with secondary systemic capillary leak syndrome : A case report.
Sjögren's syndrome concurrent with protein-losing gastroenteropathy can develop into secondary systemic capillary leak syndrome. Thus, it is important to diagnose the condition as soon as possible and simultaneously administer treatment for Sjögren's syndrome, protein-losing gastroenteropathy, and systemic capillary leak syndrome.


Stability of low-concentration ceftazidime in 0.9% sodium chloride injection and balanced salt solutions in plastic syringes under various storage conditions.
The objective of this study was to assess the stability of ceftazidime in 0.9% sodium chloride injection and balanced salt solutions. Ceftazidime was dissolved in 0.9% sodium chloride injection or balanced salt solution at a concentration of 1 mg/mL. Samples of these solutions were then stored under three different sets of conditions, ambient temperature (25 deg C), refrigeration (4 deg C), or frozen (-20 deg C). The concentration of ceftazidime in each solution was determined at various intervals using the high-performnace liquid chromatographic method outlined in the United States Pharmacopeia-National Formulary. Our results show that ceftazidime was stable (>90% concentration) for up to 72 hours in both 0.9% sodium chloride injection and balanced salt solutions at ambient temperature. Ceftazidime was stable in both solutions in the refrigerator for 17 days. No siginificant degradation was noticed for up to 60 days when the solutions were kept in the freezer.


Regulation of ACTH levels in anterior pituitary cells during stimulated secretion: evidence for aspartyl and cysteine proteases in the cellular metabolism of ACTH.
The regulation of cellular levels of adrenocorticotropin hormone (ACTH) in response to stimulated secretion was investigated to define the extent of cellular depletion of ACTH and subsequent increases to replenish ACTH levels in anterior pituitary cells (in primary culture). Treatment of cells with secretagogues for short-term incubation times (hours) resulted in extensive depletion of cellular ACTH. Corticotropin releasing factor (CRF) induced depletion of cellular levels of ACTH by 60-70% of control levels. The CRF-induced reduction of cellular ACTH was inhibited by the glucocorticoid dexamethasone. Phorbol myristate acetate (PMA), which stimulates protein kinase C (PKC), reduced ACTH levels by 50-60%. Forskolin, a stimulator of cAMP production, produced a moderate reduction in cellular ACTH. During prolonged incubation of cells (2 days) with these secretagogues, further reduction of ACTH levels by 70-80% was observed. However, increased cellular levels of ACTH occurred with continued treatment of cells with secretagogues, which provided nearly complete replenishment of cellular ACTH after 5 days treatment with secretagogues. Notably, the rising levels of cellular ACTH were inhibited by the aspartyl protease inhibitor acetyl-pepstatin A, and by the cysteine protease inhibitor E64d. These results demonstrate that depletion and recovery of ACTH levels are coordinately regulated, and that the increases in cellular levels of ACTH during the recovery phase involves participation of aspartyl and cysteine proteases. Thus, aspartyl and cysteine proteases may be involved in the cellular metabolism of ACTH.


CD14 overexpression upregulates TNF-α-mediated inflammatory responses and suppresses the malignancy of gastric carcinoma cells.
CD14 mediates the inflammatory response via recognition of lipopolysaccharide, which has been implicated in Helicobacter pylori (H. pylori) infections. Increasing evidence has suggested that CD14 status significantly influences the clinical outcome of H. pylori infection, which can result in gastric carcinoma. However, there is little evidence regarding the cellular impact and associated molecular basis of CD14 on gastric carcinoma cells. To address this question, we generated a CD14-overexpressing SGC-7901 gastric carcinoma cell line and analyzed the impact of CD14 expression. Our results revealed that cells overexpressing CD14 exhibited antitumor potential, including significantly decreased clonogenic ability, proliferation, metastatic invasion, as well as enhanced apoptosis, suggesting a tumor-suppressive role of CD14 in the cells. Intriguingly, we further discovered that CD14 overexpression activated NF-κB via upregulating its expression and simultaneously stimulating DNA binding activity. Upregulated NF-κB transcriptionally elevated a series of pro-inflammatory cytokines, including TNF-α, IL-1β, IL-6, and IL-12. Together, the current study utilized a CD14-overexpressing gastric cell model to determine the impacts of CD14 upregulation on cell viability, apoptosis, and migration and NF-κB-mediated inflammation.


The Economic and Humanistic Burden of Severe Sepsis.
Sepsis and severe sepsis in particular remain a major health problem worldwide. Their cost to society extends well beyond lives lost, as the impact of survivorship is increasingly felt. A review of the medical literature was completed in MEDLINE using the search phrases "severe sepsis" and "septic shock" and the MeSH terms "epidemiology", "statistics", "mortality", "economics", and "quality of life". Results were limited to human trials that were published in English from 2002 to 2014. Articles were classified by dominant themes to address epidemiology and outcomes, including quality of life of both patient and family caregivers, as well as societal costs. The severity of sepsis is determined by the number of organ failures and the presence of shock. In most developed countries, severe sepsis and septic shock account for disproportionate mortality and resource utilization. Although mortality rates have decreased, overall mortality continues to increase and is projected to accelerate as people live longer with more chronic illness. Among those who do survive, impaired quality of life, increased dependence, and rehospitalization increase healthcare consumption and, along with increased mortality, all contribute to the humanistic burden of severe sepsis. A large part of the economic burden of severe sepsis occurs after discharge. Initial inpatient costs represent only 30 % of the total cost and are related to severity and length of stay, whereas lost productivity and other indirect medical costs following hospitalization account for the majority of the economic burden of sepsis. Timeliness of treatment as well as avoidance of intensive care unit (ICU)-acquired illness/morbidity lead to important differences in both cost and outcome of treatment for severe sepsis and represent areas where improvement in care is possible. The degree of sophistication of a health system from a national perspective results in significant differences in resource use and outcomes for patients with serious infections. Comprehensive understanding of the cost and humanistic burden of severe sepsis provides an initial practical framework for health policy development and resource use.


Non-opiate beta-endorphin fragments and dopamine--III. gamma-Type endorphins and various neuroleptics counteract the hypoactivity elicited by injection of apomorphine into the nucleus accumbens.
The hypoactivity in rats induced by small doses of apomorphine, injected bilaterally into the nucleus accumbens area of the brain, could be antagonized by pretreatment with the neuroleptic-like neuropeptide des-enkephalin-gamma-endorphin (DE gamma E, beta-endorphin 6-17) as well as with the neuroleptic drugs haloperidol, sulpiride and clozapine injected into the accumbens. Dose-response studies revealed that a dose of 100 pg DE gamma E completely inhibited the apomorphine-induced hypomotility. The influence of DE gamma E appeared to be specific for gamma-type endorphins, since alpha-type endorphins were inactive in this respect. Treatment with DE gamma E injected into the accumbens for 4 days resulted in an enhancement of apomorphine-induced hypoactivity. It is concluded that gamma-type endorphins may control the activity of dopaminergic transmission in the nucleus accumbens, a suggestion which may be of significance for the purported neuroleptic-like and antipsychotic action of gamma-type endorphins.


Instruments measuring community pharmacist role stress and strain measures: A systematic review.
While macro and meso approaches to implementing public health initiatives in community pharmacies have been studied, the micro perspective of their pharmacist providers requires more inspection. Community pharmacists report increasing stress, overload, and limited control over facets of their work.1-7 Social exchange principles, e.g. role price, may help to typify pharmacist work decisions so problematic situations can be modified, thus protecting workforce health. To do so, the underlying pressures of the pharmacist role (i.e. role stresses) and indicators of systemically-caused strain (i.e. role strains) should be measurable. To summarise validated and reliable instruments used to measure role stress and strain among community pharmacists and evaluate compatibility in testing a theoretically-derived framework. In April 2020, journal articles describing reliable and validated instruments measuring role stress and strain responses among community pharmacists were identified from an online search via Scopus, Web of Science and PubMed. English-language articles after 1990 were selected; duplicates were deleted. Inclusion and exclusion criteria were used to screen title/abstracts and full texts. Reference lists were manually searched. Resultant instruments were analysed for theoretical compatibility. After review, 26 separate instruments were found: seven psychological strain instruments, 14 social strain response instruments, and five role stress instruments. Role stresses were often present as facet-specific dimensions in psychological and social strain instruments. Strain instruments measuring individual evaluation of work were compatible with a social exchange approach. Twenty-six reliable and validated instruments measuring role stress and role strain were found to measure negative role outcomes from the micro community pharmacist perspective. Structural measurement of role stress and resultant negative responses enable detailed examination into pharmacist roles and insights into pharmacist behaviour. Further research is required to develop additional role stress and strain instruments, and to discover pharmacist role benefits and their influence.


Ferning in conjunctival-cytologic preparations. Crystallisation in stained semiquantitative pipette samples of conjunctival fluid.
Two quantitative pipette samples and 3 smears from each of 305 eyes were re-evaluated. Two types of ferning (F) were detected i.e. rectangular (FR) and acute-angled (FA) ramifications, respectively. One FR corresponds in area to 0.11 FA. Ferning was present in 29% of pipette samples, averaging 0.41 mm2 in the form of FR in the total series. Ferning was most frequent in samples with fairly large amounts of mucus, more frequent in neutrophilia than in lymphocytosis, and the rarest in normal cytology. F was seen in several cases of acute infections conjunctivitis (55%), neonatal and follicular conjunctivitis, and keratitis, whereas it was rare in normal eyes (7%). This distribution is presumably due to the amount of mucus in the samples preserving the F-pattern during the preparation procedure. F was rarely seen in smears (0.7%).


Three-dimensional reformations of computed tomography in the assessment of facial trauma.
Three-dimensional (3D) computed tomography (CT) reformations were obtained in 15 patients presenting with facial injuries of differing severity. The 3D images were compared with standard radiographs and high resolution CT, including multiplanar reformations, and assessed under the headings of fracture detection, extent and displacement using a simple scoring system. 3D was valuable in severe trauma with multiple fractures, providing a clear demonstration of fraction extent and fragment displacement. 3D was much less useful in minor trauma in which little or no fragment displacement had occurred, and demonstrated fewer fractures overall than either radiography or CT in all categories of facial injury. When used as part of a high resolution CT examination 3D imaging can provide useful information to both radiologist and surgeon in cases of severe facial trauma.


TSPYL1 regulates steroidogenic gene expression and male factor fertility in mice.
To determine the importance of testis-specific, Y-encoded-like 1 (TSPYL1) in survival and male factor fertility in mice. Experimental prospective study. Research laboratories in a university medical faculty. We generated Tspyl1 knockout (KO) mouse lines by CRISPR/Cas9. The lines were maintained by pairing heterozygous mice to provide wild-type control and KO males for comparison. None. Mendelian ratio, body and testis weight, histology, sperm motility, mating tests, pregnancy outcome, transcript levels of genes for testosterone production, and serum testosterone level. A variable percentage of Tspyl1 KO mice survived beyond weaning depending on the genetic background. Growth around weaning was retarded in KO mice, but the testes-to-body weight ratio remained normal and complete spermatogenesis was revealed in testis histology. Sperm was collected from the cauda epididymis, and a significantly smaller percentage of sperm was progressively motile (22.3% ± 18.3%, n = 14 samples) compared with wild type (58.9% ± 11.5%, 11 samples). All 11 KO mice tested had defective mounting behavior. From 11 KO males paired with a total of 88 females, only one litter was born, compared with 53 litters sired by 11 age-matched wild-type males. Expression of Star, Cyp11a1, Cyp17a1, Hsd3b6, and Hsd17b3 in the KO testis was significantly reduced, while serum testosterone level was within the normal range. TSPYL1 is critical for survival and reproductive success in mice. TSPYL1 enhances the expression of key steroidogenic genes in the mouse testis.


Mutations induced by benzo[a]pyrene diolepoxide at the hprt locus in human T-lymphocytes in vitro.
Human T-lymphocytes have been treated with benzo[a]pyrene diolepoxide (BPDE) in vitro and T-cell clones mutated in the hprt gene have been isolated. The mutant frequencies in BPDE-treated T-cell cultures were on average 24-fold higher than those of untreated cultures. Thus, BPDE is a potent inducer of gene mutation in this system. In order to examine which types of mutations are induced by BPDE in human cells, 41 spontaneous and 44 BPDE-induced mutant clones have been characterized using the Southern blot technique. In addition, rearrangements of the T-cell-receptor beta and gamma loci have been used to determine the proportion of isolated clones that are unique, and thus likely to represent independent mutational events. Out of 23 independent spontaneous mutants 4 had large hprt alterations that could be detected on Southern blots. Two of these alterations, deletions of exons 2-6, have been confirmed using PCR of hprt cDNA and direct sequencing of the PCR product. All 33 independent BPDE-induced mutants had normal hprt restriction patterns which indicates that BPDE is mainly a point mutagen in this system.


Identifying children and adolescents at ultra high risk of psychosis in Italian neuropsychiatry services: a feasibility study.
The past 20 years have seen the evolution of the construct of a clinical high-risk (hereafter, HR) state for psychosis. This construct is designed to capture the pre-psychotic phase. Some aspects of this approach, such as its feasibility in children and adolescents, are still under investigation. In the present study, we address the feasibility of implementing prodrome clinics for HR individuals within the framework of Italy's national child and adolescent neuropsychiatry services and the clinical relevance of a HR diagnosis in this population. Using the Comprehensive Assessment of At-Risk Mental States (CAARMS) to identify help-seeking patients meeting at least one HR criterion at baseline (HR+), we recruited 50 subjects for a feasibility study. The results obtained show that the Italian version of the CAARMS is easily administrable, causing patients no substantial discomfort. The prevalence of HR+ in our cohort was 44 %, which increased by an additional 18 % when negative symptoms were considered as an experimental inclusion criterion (HRNeg). The HR+ subjects were significantly more impaired in their social and occupational functioning than their HR- peers (subjects not at HR). The cumulative 1-year transition risk of psychosis of the HR+ group was 26.7 %. When the HRNeg group was added, the 1-year transition risk was 17.3 %. We suggest that administration of the CAARMS to children and adolescents with putative prodromal psychosis is feasible and that this assessment can easily be integrated into existing Italian neuropsychiatry services although clinicians should interpret results with caution as results in this age group still have to be replicated.


Efficacy and safety of galcanezumab as a treatment of refractory episodic and chronic cluster headache: Case series and narrative review.
Galcanezumab, a monoclonal antibody targeting calcitonin gene-related peptide (CGRP), has demonstrated clinical benefit as a preventive treatment of episodic cluster headache (ECH) but not in chronic cluster headache (CCH) to this date. Our objective was to analyze our clinical experience of the compassionate use of galcanezumab in cluster headache and to conduct a narrative review of the published literature. We present a case series of patients with refractory ECH and CCH treated with 240 mg galcanezumab monthly in an outpatient headache clinic. We recorded epidemiologic and clinical data and analyzed the disease evolution after 3 and 6 months. The review was performed following the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. We included three patients with ECH who were treated during a refractory cluster bout (mean duration of 83.7 days since the first attack, range 46.0-105.0 days) and six patients with CCH who had a high frequency of attacks (mean 35.8 attacks/week, range 7-56) and refractory to a mean of 5.2 preventive treatments (range, 3-9). In the CCH group, >50% frequency reduction was seen in 83% (5/6 patients) and the number of attacks per week showed a mean reduction of -24.2 at month 3 (range, -6 to -49) and -27.6 at month 6 (range, -7 to -49). In the ECH group, the bout ended a mean 17.3 days (range, 10-28) after galcanezumab administration. One third of patients reported mild adverse events, none of them leading to discontinuation. In conclusion, our clinical experience supports the use of galcanezumab in patients with refractory cluster headache. These results might encourage the possibility of continuing clinical development with randomized controlled trials of anti-CGRP treatments in patients with cluster headache.


Cross-protection of Lactococcus lactis-displayed HA2 subunit against homologous and heterologous influenza A viruses in mice.
Current influenza vaccines provide strain-specific protection against homologous subtypes and need to be updated annually. Therefore, it is essential to develop a universal vaccine that would induce broadly cross-protective immunity against homologous and heterologous influenza A viruses. The highly conserved HA2 subunit is a promising candidate for developing a universal influenza vaccine. Here, we hypothesized that the HA2 subunit could be displayed on the surface of Lactococcus lactis (L. lactis), using Spax as an anchor protein (L. lactis/pNZ8008-Spax-HA2) and that L. lactis/pNZ8008-Spax-HA2 would have immunogenicity by oral administration without the use of adjuvant in the mouse model. To address this hypothesis, we show that oral vaccination of mice with L. lactis/pNZ8008-Spax-HA2 elicited significant humoral and mucosal immune responses. Importantly, L. lactis/pNZ8008-Spax-HA2 provided 100% protection against homologous H5N1 or heterologous H1N1 virus challenge. These results suggest that an HA2 subunit presented on the surface of L. lactis is an effective universal vaccine candidate against influenza A viruses in the poultry industry and in humans.


Precise water vapor pressure value calculations.
Precise values for water vapor pressure in saturated systems may be computed using the Goff-Gratch equation. This equation has been adapted for convenient use on microcomputers. A Microsoft BASIC listing of the programming version of the equation is presented. This BASIC version may be easily translated into other high level programming languages and thus is suitable for use on many computer systems for routine laboratory computations.


Mobbing perception among Intensive Care Unit nurses.
to determine the perception of intensive care unit nursing staff on mobbing. qualitative approach study, Grounded Theory was used, 12intensive care unit nurses of 2public hospitals in our country during December 2017. female sex predominated with an average age of 41.33 years old, mostly married, on night shift and trained a nursing technicians; 4categories emerged: general knowledge about mobbing, the origin of mobbing and its main actors, experiences of mobbing as a victim and as a spectator and the implications of mobbing in working life. issues of workplace harassment are sensitive for most health workers, since they deal with private situations and lack of support from superiors when they have been victims of harassment. The evidence shows that one of the reasons why mobbing can be perceived in different ways is because little is known about the real concept, it can be associated with multiple forms of violence and there is heterogeneity in the use of the term. the majority of intensive care unit nursing staff have been victims and witnesses of mobbing behaviour, with negative repercussions on their job satisfaction and performance; It is also the cause of constant staff turnover.


Lack of an association between XRCC2 R188H polymorphisms and breast cancer: an update meta-analysis involving 35,422 subjects.
Several studies have investigated the associations between XRCC2 R188H polymorphism and the susceptibility to breast cancer, but the results have been inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. PubMed and China National Knowledge Infrastructure (CNKI) searches were carried out for relevant studies published before March 2015. Meta-analysis was performed with the Stata, version 11.0. A total of 17 case-control studies, including 17,986 cases and 17,436 controls, were selected. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the homozygous model, dominant model, and recessive model. When all the studies were pooled into the meta-analysis, there was no evidence showing a significant association between XRCC2 R188H polymorphism and breast cancer risk (for homozygous model, OR=0.84, 95% CI=0.62-1.14; for dominant model: OR=0.76, 95% CI=0.53-1.09; and for recessive model: OR=1.04, 95% CI=0.98-1.10). In the subgroup analysis by ethnicity, no significant association was found between the polymorphism and breast cancer risk. In conclusion, this meta-analysis indicates that the XRCC2 R188H polymorphism is not a risk factor for developing of breast cancer.


Iqmik--a form of smokeless tobacco used by pregnant Alaska natives: nicotine exposure in their neonates.
To determine the concentration of nicotine and cotinine in maternal blood and neonatal cord blood among pregnant Alaska Native women and to assess the neonates for neurobehavioral effects. In a nonrandomized, clinical observational pilot trial, 60 pregnant Alaska Native women were enrolled for assessment of Iqmik (a mixture of leaf tobacco and ash) and other tobacco use during pregnancy and at delivery. Neonatal cord blood, nicotine and cotinine concentrations were obtained, and neonatal neurobehavioral effects were assessed using the Lipsitz scale. At delivery, there were 22 subjects who reported using only Iqmik, and 10 who used other tobacco products. Subjects who reported using only Iqmik prior to delivery had higher concentrations of cotinine (167+/-116 vs. 81+/-100) in maternal blood (rank sum test, p=0.036) and higher concentrations of nicotine (8.4+/-7.3 vs. 4.4+/-5.1, p=0.048) and cotinine (153+/-115 vs. 70+/-95, p=0.048) in cord blood compared to subjects who reported using other tobacco products. Neurobehavioral signs as assessed by the Lipsitz score were increased in neonates born to mothers using only Iqmik (3.7+/-1.8, p=0.011), or to mothers using other tobacco products (3.4+/-1.4, p=0.034) compared to neonates born to women who reported no tobacco use (1.8+/-1.4). Mothers who use Iqmik and their neonates have higher cotinine concentrations compared to mothers who use cigarettes and/or other forms of tobacco. Neurobehavioral signs occur in neonates born to women who use Iqmik but also in neonates born to mothers who use other forms of tobacco during pregnancy.


The effect of New York's seat belt use law on teenage drivers.
This study assessed the effects of New York State's recently adopted mandatory seat belt use law on teenage drivers. Teenage drivers were observed as they entered high school parking lots before the law was adopted, after it was adopted but before it was effective, one month after the effective date, and again five months after the effective date. The results showed that 14% of the teenage drivers were wearing either shoulder or lap belts or both prior to adoption of the law. This increased to 22% after adoption of the law, 60% one month after the effective date of the law, and 63% five months after the effective date. Teenagers using seat belts were more often female, were younger, had completed driver education and had a longer trip from home to school. Both before and after the law, teenage belt use was similar to, but typically lower than, belt use in the community in which the school was located.


Testicular function in patients with familial Mediterranean fever on long-term colchicine treatment.
Sperm counts and hormonal studies were carried out in six patients with familial Mediterranean fever who were receiving long-term colchicine therapy. The duration of therapy ranged between 7 and 31 months. In all subjects, spermograms, testosterone, follicle-stimulating hormone, luteinizing hormone, and prolactin levels were within normal limits.


Dexrazoxane (ICRF-187).
1. Dexrazoxane (ICRF-187) is the only clinically approved drug for use in cancer patients to prevent anthracycline mediated cardiotoxicity. 2. The mode of action appears to be mainly due to the potential of the drug to remove iron from iron/anthracycline complexes and thus reduce free radical formation by these complexes. 3. Dexrazoxane also influences cell biology by its ability to inhibit topoisomerase II and its effects on the regulation of cellular iron homeostasis. 4. Although the cardioprotective effect of dexrazoxane in cancer patients undergoing chemotherapy with anthracyclines is well documented, the potential of this drug to modulate topoisomerase II activity and cellular iron metabolism may hold the key for future applications of dexrazoxane in cancer therapy, immunology, or infectious diseases.


Mechanisms of seedling mortality by subterranean insect herbivores.
The nature of the mortality of germinating seeds of Vicia sativa, the common vetch, was investigated in a pot trial under controlled conditions. Chafer and tipulid larvae were restricted by nylon mesh partitions to enable radicle and/or hypocotyl herbivory to occur. The effects of the two insects were very similar. In control situations, an average of 88% of the viable seed sown recruited successfully. Hypocotyl and radicle herbivory had similar effects on seedling mortality, with recruitment of viable seed sown being reduced to 52%. When both modes of attack occurred together, successful recruitment was only 34%. Feeding on both plant parts resulted in an average post-emergence mortality of 14% of the seed sown, but the effect on pre-emergence mortality was of greater importance, amounting to 41%. The mechanisms by which soil-dwelling herbivores may cause seedling mortality in the field are discussed.


Haplotype association and synergistic effect of human aldosterone synthase (CYP11B2) gene polymorphisms causing susceptibility to essential hypertension in Indian patients.
Aldosterone synthase (CYP11B2) is a key enzyme involved in the terminal steps of aldosterone biosynthesis. Genetic variability in CYP11B2 gene has been associated with heterogeneous aldosterone production, which can affect sodium homeostasis and thereby regulation of blood pressure. Hence, the present study was aimed to explore the single-locus variations, haplotype and epistasis patterns of CYP11B2 (C-344T, intron-2 gene conversion and Lys173Arg) gene polymorphisms, and the risk contributed by them to the development of essential hypertension (EHT). A total of 279 hypertensive patients and 200 normotensive controls were enrolled in this study. C-344T and Lys173Arg polymorphisms of CYP11B2 gene were genotyped by PCR-RFLP method and intron-2 gene conversion (IC) polymorphism by allele-specific PCR analysis. Single-locus analysis revealed significant association of CYP11B2 C-344T and Lys173Arg polymorphisms with EHT (p < 0.05). Considering the sexes, Lys173 allele was found to be at risk for hypertension in males (OR 1.40; 95% CI = 1.01-1.96). Unphased haplotype analysis revealed H1 (T-Conv-Lys; p = 0.0017) to have significant risk for EHT, while haplotype H4 (T-Wt-Arg) had a significant protective effect. Multifactor dimensionality reduction (MDR) interaction analysis found the overall best model with C-344T and IC polymorphisms exhibiting strong synergistic effect. The present study revealed a strong synergistic effect of CYP11B2 C-344T and IC polymorphisms causing susceptibility to EHT and haplotype H1 (-344T-Conv-Lys173) as the risk-conferring factor for hypertension predisposition.


A case of mitochondrial disease with severe left ventricular hypertrophy.
A 35-year-old woman was admitted for progressive dyspnea with lower limb edema. Transthoracic echocardiography showed severe left ventricular hypertrophy (LVH) and heart failure with preserved ejection fraction (HFPEF). Electron microscopy of an endomyocardial biopsy sample revealed a high density of mitochondria of abnormal size and shape. We report a case of mitochondrial disease with severe LVH and HFPEF.


Characterization of cryptic plasmids from marine cyanobacteria and construction of a hybrid plasmid potentially capable of transformation of marine cyanobacterium, Synechococcus sp., and its transformation.
Among forty strains of marine cyanobacteria isolated in our laboratory, five strains had 1-3 different plasmids. The unicellular marine cyanobacterium, Synechococcus sp. NKBG 042902, contains at least three plasmids (pSY09, pSY10, and pSY11). However, these plasmids are cryptic. Therefore, a hybrid plasmid pUSY02 containing the 1.4-kb HindIII fragment of pSY11 and Escherichia coli plasmid pUC18 was constructed. The plasmid pUSY02 transformed both marine Synechococcus sp. NKBG042902-YG1116, which is a cured strain, and fresh water Anacystis nidulans R2 by dark incubation or Ca2+ treatment. However, the plasmid pSG111 constructed from the plasmid DNA of A. nidulans R2 failed to transform marine Synechococcus sp. Electroporation was also applicable to transformation of marine Synechococcus sp. and fresh water A. nidulans R2. The plasmid pUSY02 was rapidly introduced into marine Synechococcus sp.


Six-month intragastric balloon treatment for obesity improves lung function, body composition, and metabolic syndrome.
The purpose of this study is to establish whether the use of an intragastric balloon (IGB) for 6 months improves lung function, metabolic parameters, and body fat distribution in patients with overweight/obesity and metabolic syndrome (MS). This is a longitudinal and interventional study on 40 adults, whose anthropometric, laboratory, and lung function parameters were assessed and who underwent dual-energy X-ray absorptiometry (DXA) before implantation and after removal of IGB. The total lung capacity (TLC) (p = 0.0001), functional residual capacity (FRC) (p = 0.0001), residual volume (p = 0.0005), and expiratory reserve volume (ERV) (p = 0.0001) were significantly reduced by IGB. The body mass index (BMI) significantly decreased from a median of 39.1 kg/m(2) at the beginning of the study to 34.5 kg/m(2) at the end of the 6-month period (p = 0.0001). At the end of the study, 31 participants (77.5%) no longer met the diagnostic criteria of MS. The percentage of truncal, android, gynoid, and total fat investigated by DXA exhibited significant reductions (p = 0.0001). Significant correlations were found between delta TLC and delta waist circumference (ρ = -0.34; p = 0.03), delta FRC and delta IMC (ρ = -0.39; p = 0.01), delta ERV and delta BMI (ρ = -0.44; p = 0.005), and delta ERV and delta high-density lipoprotein (HDL) (ρ = -0.37; p = 0.02). Significant correlations were also found between delta ERV and delta truncal (ρ = -0.51; p = 0.004), android (ρ = -0.46; p = 0.01), gynoid (ρ = -0.55; p = 0.001), and total fat (ρ = -0.59; p = 0.0005). IGB efficiently induced weight loss and promoted the improvement of lung function parameters, with a reduction of the restrictive ventilatory defect. It also promoted improvements of MS and the pattern of body fat distribution.


Grip strength as a predictor of depressive symptoms among vulnerable elderly Europeans with musculoskeletal conditions.
The present study aimed to investigate the grip strength (GS) discrimination capacity and cutoffs points for depressive symptoms among vulnerable elderly individuals with musculoskeletal conditions. The Survey of Health, Aging, and Retirement in Europe wave 6 was analyzed. GS was measured by a handgrip dynamometer, and EURO-D scale was used to assess depressive symptoms. GS cutoff values for depressive symptoms were calculated using the receiver operating characteristics curve. 2206 participants, mean age 74.0 (73.7-74.3), 78.8% with osteoarthritis/other rheumatism, enrolled in the study. Sensitivity varies between 0.44 (men, ≥ 85 years) and 0.82 (men, 75-84 years), and specificity varying between 0.35 (women, 75-84 years) and 0.70 (men 75-84 years). GS is associated with depressive symptoms just for women and it is not possible to use a GS cutoff point for screening depressive symptoms for vulnerable men and women with musculoskeletal conditions over the age of 65 years.


PdeHCA2 affects biomass in Populus by regulating plant architecture, the transition from primary to secondary growth, and photosynthesis.
PdeHCA2 regulates the transition from primary to secondary growth, plant architecture, and affects photosynthesis by targeting PdeBRC1 and controlling the anatomy of the mesophyll, and intercellular space, respectively. Branching, secondary growth, and photosynthesis are vital developmental processes of woody plants that determine plant architecture and timber yield. However, the mechanisms underlying these processes are unknown. Here, we report that the Populus transcription factor High Cambium Activity 2 (PdeHCA2) plays a role in the transition from primary to secondary growth, vascular development, and branching. In Populus, PdeHCA2 is expressed in undifferentiated provascular cells during primary growth, in phloem cells during secondary growth, and in leaf veins, which is different from the expression pattern of its homolog in Arabidopsis. Overexpression of PdeHCA2 has pleiotropic effects on shoot and leaf development; overexpression lines showed delayed growth of shoots and leaves, reduced photosynthesis, and abnormal shoot branching. In addition, auxin-, cytokinin-, and photosynthesis-related genes were differentially regulated in these lines. Electrophoretic mobility shift assays and transcriptome analysis indicated that PdeHCA2 directly up-regulates the expression of BRANCHED1 and the MADS-box gene PdeAGL9, which regulate plant architecture, by binding to cis-elements in the promoters of these genes. Taken together, our findings suggest that HCA2 regulates several processes in woody plants including vascular development, photosynthesis, and branching by affecting the proliferation and differentiation of parenchyma cells.


You're the Flight Surgeon: white matter hyperintensities.
Park B. You're the flight surgeon: white matter hyperintensities. Aerosp Med Hum Perform. 2015; 86(12):1075-1077.


Progress and outlook of Sn-Pb mixed perovskite solar cells.
Organic-inorganic hybrid perovskites have revolutionized solar cell research owing to their excellent material properties. Most previous research has been done on Pb-based perovskites. Recently, efforts to discover a Pb-free or Pb-less perovskite material with an ideal bandgap ranging 1.1-1.3 eV have led researchers to investigate Sn-Pb mixed perovskites. Sn-Pb mixed perovskites have a bandgap of ~ 1.25 eV, which is suitable for high-efficiency single-junction and perovskite/perovskite tandem solar cells. Moreover, the Pb content of Sn-Pb mixed perovskites is 50-60% lower than that of Pb-based perovskites, partially mitigating the Pb toxicity issue. However, incorporating Sn2+ into the crystal structure also causes various drawbacks, such as inhomogeneous thin film morphologies, easy oxidation of Sn2+, and more vulnerable surface properties. Researchers have made substantial progress in addressing these challenges through improvements in compositional design, structural optimization, precursor design, and surface treatments. In this review, we provide a comprehensive overview of the progress in Sn-Pb mixed perovskite solar cells. Furthermore, we analyze the key variables and trends as well as provide an outlook for future directions in the research on Sn-Pb mixed perovskites.


Platelet imipramine binding in patients with panic disorder and major familial depression.
Platelet 3H-imipramine binding was investigated in 15 normal subjects, 17 patients with major depressive disorder and 43 patients with panic disorder, to further study the relationship between depressive and anxiety disorders. Whereas patients with major depression had a significantly lower mean Bmax value than healthy volunteers, mean Bmax values in patients with panic disorder did not differ significantly from normal controls. Furthermore, apparently normal Bmax values were observed even in those panic disorder patients who had concurrent major depression or a past history of depression. Thus, despite previous findings of an overlap between panic and depressive disorders, the present results suggest that the two syndromes may have distinct neurochemical substrates.


A study of factors affecting the sensitivity of the passive haemagglutination method for serotyping Campylobacter jejuni and Campylobacter coli and recommendations for a more rapid procedure.
Factors affecting the sensitivity of the passive haemagglutination method for serotyping campylobacters have been studied. The concentration of red blood cells during the haemagglutination stage of the procedure markedly affected the titer obtained. An increase in concentration of red blood cells resulted in a lower titer, with titers being inversely proportional to red blood cell concentration. No differences in titer were observed when erythrocytes were sensitized at a range of pH values between pH 5.0 and pH 8.0. The time required for antigen extraction and for red blood cell sensitization was shown to be 15 min each, thus resulting in a reduction in the time required for serotyping. Furthermore, use of avian erythrocytes enabled the haemagglutination reactions to be read after incubation for only 1 h. Combining these procedures with a rapid slide haemagglutination test enables a single worker to serotype over 100 C. jejuni and C. coli isolates within 1 working day.


The biphenyl-carboxylate derivative ABD328 is a novel orally active antiresorptive agent.
We previously described a novel series of biphenyl carboxylic acid derivatives which have potent antiresorptive effects in vitro and in vivo and do not affect osteoblast function. However, none of the previous compounds showed oral activity, probably because they were esters, which would be expected to be metabolized very rapidly. Here, we tested whether derivatives where the ester link was replaced by a ketone link were orally active. Compounds were tested in murine osteoclast and osteoblast cultures and in the mouse ovariectomy (OVX) model of osteoporosis. The ketones were at least as potent at inhibiting osteoclast formation and RANKL signaling in vitro as the esters and did not inhibit osteoblast differentiation or function. The basic ketone-linked compound ABD68 was only partially able to inhibit OVX-induced bone loss at an oral dose of 20 mg/kg daily. Substitutions on the phenyl rings increased the potency of the compounds in vitro and may prevent metabolism of the compounds in vivo. The most promising derivative, ABD328, completely prevented OVX-induced bone loss when administered by intraperitoneal injection at 3 mg/kg daily. Furthermore, ABD328 was also able to fully prevent OVX-induced bone loss when given orally at 10 mg/kg daily. The results indicate that biphenyl carboxylates like ABD328 are oral candidate drugs for the treatment of diseases characterized by increased bone resorption, such as postmenopausal osteoporosis.


RETRACTED: LSAMP-AS1 binds to microRNA-183-5p to suppress the progression of prostate cancer by up-regulating the tumor suppressor DCN.
This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the editor after publication concerns were raised with respect to data presented in Figure 2. The journal contacted Southern Medical University, Guangzhou, Guangdong Province, China, who formed an Academic Committee to investigate. According to the "Academic Ethics and Implementation Rules" of Southern Medical University, the Committee reported evidence of improper preservation of original data and incorrect use of pictures, and recommended immediate withdrawal of the paper. Specifically, in the PC-3 group of Fig. 2H, the 'Control' cell migration image had been partially duplicated in the 'Empty vector' image. As per journal policy, original files used to create the entire figure were requested. Raw western blot images were not available for Figure 2 C+F, and experimental repeats yielded protein level discrepancies with the original published data. The editors therefore no longer have confidence in the integrity of these data.


Evidence for macromolecular synthesis in stimulation of the estrogen synthesizing system of the immature rat ovary by PMS.
Exposure of immature rat ovaries to pregnant mare's serum gonadotropin (PMS) results in a prompt increase in testosterone and progesterone output but synthesis of estradiol (E2) increases only after a lag period of several hours. Actinomycin D (Act-D) given with PMS did not inhibit testosterone or progesterone production but the estrogenic response was prevented. Delay in administration of the Act-D until 12 hr after PMS resulted in a transient increase in E2 secretion lasting less than 12 hrs. When Act-D was given 12, 16 or 20 hrs after PMS, and ovarian steroid production measured by a one hr incubation, no inhibition of progesterone, testosterone or E2 was found; the synthesis of the latter two steroids was increased by the drug. Cycloheximide, on the other hand, was most effective at inhibiting testosterone and E2 production when it was given at 12 hrs; the drug was progressively less effective in lowering production of these steroids when it was given at 16 or 20 hrs. Cycloheximide did not alter progesterone production unless it was given at the same time as PMS. The results are consistent with the view that the induction of the estrogen synthesizing system of the immature rat ovary by gonadotropin involves, during the first 12 hrs, production of a material sensitive to Act-D inhibition (mRNA?) and then production of a material sensitive to cycloheximide inhibition (protein-enzymes?). The continued production of both of these materials appears to require the continual presence of gonadotropin.


Individual patient diagnosis of AD and FTD via high-dimensional pattern classification of MRI.
The purpose of this study is to determine the diagnostic accuracy of MRI-based high-dimensional pattern classification in differentiating between patients with Alzheimer's disease (AD), Frontotemporal Dementia (FTD), and healthy controls, on an individual patient basis. MRI scans of 37 patients with AD and 37 age-matched cognitively normal elderly individuals, as well as 12 patients with FTD and 12 age-matched cognitively normal elderly individuals, were analyzed using voxel-based analysis and high-dimensional pattern classification. Diagnostic sensitivity and specificity of spatial patterns of regional brain atrophy found to be characteristic of AD and FTD were determined via cross-validation and via split-sample methods. Complex spatial patterns of relatively reduced brain volumes were identified, including temporal, orbitofrontal, parietal and cingulate regions, which were predominantly characteristic of either AD or FTD. These patterns provided 100% diagnostic accuracy, when used to separate AD or FTD from healthy controls. The ability to correctly distinguish AD from FTD averaged 84.3%. All estimates of diagnostic accuracy were determined via cross-validation. In conclusion, AD- and FTD-specific patterns of brain atrophy can be detected with high accuracy using high-dimensional pattern classification of MRI scans obtained in a typical clinical setting.